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The brain is frequently a site of disease relapse in Non-Small Cell Lung Cancer (NSCLC) patients. For radically treated patients, stage III has the highest risk for brain metastases with a cumulative incidence of brain metastases after radical treatment of approximately 30% for which there is no cure at the moment, decreasing the long-term survival and Quality of Life. Strategies to reduce incidence of brain metastases are necessary.~Prophylactic Cranial Irradiation (PCI) has been shown to reduce the incidence of brain metastases in patients with NSCLC. However, PCI leads to a neurocognitive impairment in about 25% of patients without altering the QoL.~The addition of durvalumab after chemo-radiotherapy in stage III NSCLC could reduce the incidence of brain metastases. In pre-clinical models, immunotherapy potentiates the effects of radiotherapy by a factor two to five. This makes the combination of PCI and immunotherapy interesting to evaluate whether it can further decrease the percentage of brain metastases as well as preserve organ function as a lower radiation dose can probably be used when combined with an antiprogrammed death (ligand)1 (PD(L)-1).~The hypothesis of the NVALT28 trial is that the combination of PCI with durvalumab will decrease the incidence of brain metastases from 30% to 15 % with durvalumab and to a maximum of 5% with the addition of low-dose PCI. This strategy would make brain metastases in stage III NSCLC history and this would improve QoL.

This trial studies the combination of low-dose PCI with or without durvalumab in patients with radically treated stage III NSCLC. The hypothesis is that the incidence of brain metastases will be reduced from 30% to 15 % with durvalumab and to a maximum of 5% with the addition of low-dose PCI. This strategy would make brain metastases in stage III NSCLC history and this would improve QoL.

The serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), CA125 are often increased in interstitial lung disease patients.~This study was undertaken to investigate the source of these serum tumor markers.We hypothesis that these tumor markers are released from the lung.~The broncholveolr lvge fluid levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), CA125 were measured in the interstitial lung disease patients before lung transplantation. The immunohistochemical test was performed in the specimen lung after lung transplantation.

The serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), CA125 are often increased in interstitial lung disease patients.~This study was undertaken to investigate the source of these serum tumor markers.

The current standard of incisional hernia repair is reinforcement with permanent synthetic mesh. However, permanent synthetic mesh is contraindicated in contaminated surgical field due to higher risk of postoperative infection. In order to resist to infection, absorbable meshes, such as biological and biosynthetic meshes, have been developped. However, some controversies exist about the clinical benefit of biological meshes in the long term. Reasons for theses controversies are their overall risk of complication and recurrence and the lack of consensus in which surgical technique to apply. Moreover, the financial cost of biological meshes is very high. Recently developed, biosynthetic meshes appear to be a promising option ; Compared to biological meshes, they seem to have several advantages. However, such data demonstrating the beneficial use of biosynthetic mesh in contaminated incisional hernia repair is not available. In this regard, the COMpACT-BIO study aims to investigate the clinical and economic benefit of the use of biosynthetic mesh in contaminated incisional hernia repair in comparison to the standard of repair. This is a multicenter, prospective, longitudinal and randomized study, which also offers a standardized technique of repair.

Incisional hernia is one of the most common complications of abdominal surgery and carries a significant burden for both patients and the economic health service. However, no consensus for the surgical treatment of incisional hernia in contaminated field is currently available. The purpose of the COMpACT-BIO study is to investigate the clinical and economic benefit of the use of biosynthetic mesh in contaminated incisional hernia repair.

Severe brain injury (SBI) is one of the world's leading causes of death and disability in young adults.~Its impact on cerebral vascularization is well known. At the systemic level, it induces transient dysfunctions that can develop into severe failures, even in cases of isolated SBI. Studies on a mouse model of SBI show alterations in peripheral vascular reactivity that persist over time and are linked to endothelial dysfunction, the mechanism of which is a decoupling of endothelial NO synthase in a context of systemic inflammation. However, no data are available regarding the peripheral vascular consequences of SBI in humans.~The main objective of this prospective, monocentric, pathophysiological study is to determine whether the postocclusive hyperaemic response at the anterior surface of the contralateral forearm to the most injured cerebral hemisphere differs between patients with severe brain injury and patients with severe trauma without associated head injury matched on sex and age (+/- 5 years), by studying the amplitude of post-occlusive hyperaemia (maximum amplitude expressed as percentage of vasodilatation and area under the curve : AUC) as a function of the group.

Severe brain injury (SBI) is one of the world's leading causes of death and disability in young adults, but its peripheral vascular consequences in humans are poorly understood.~This prospective, monocentric, pathophysiological study aims to investigate differences in vasoreactivity in the anterior aspect of the contralateral forearm at the most injured cerebral hemisphere between patients with severe head trauma and patients with severe trauma without associated brain injury matched on sex and age (+/- 5 years).

This is a descriptive, observational, cross-sectional survey of participants with IBD. The survey will look into the preferences of participants towards the attributes of treatment with advanced therapies for IBD based on DCE (experimentally designed survey), including safety and efficacy profiles, frequency and RoA in a real-world setting, in European participants living with CD or UC.~The survey will involve data collection in a real-world setting via an online self-reported questionnaire hosted on the Carenity platform, an international participant community.~The survey will enroll approximately 600 participants. Participants will be enrolled in two observational cohorts:~CD Participants~UC Participants~This multi-center trial will be conducted in France, the United Kingdom, Italy, Spain, Belgium, Switzerland, the Netherlands.

The purpose of this survey is to describe Crohn's disease (CD) participants' as well as ulcerative colitis (UC) participants' preferences towards the attributes of treatment with advanced therapies for IBD, including safety and efficacy profiles, frequency and route of administration (RoA) in a real-world setting.

This is a randomized open-label study to determine the effects of monthly romosozumab for 12 month or one-time zoledronic acid infusion on bone mineral density (BMD) and biochemical markers of bone formation and resorption, in patients with spinal cord injury (SCI) and low BMD.~Patients: Thirty women between 20-70 years of age with spinal cord injury and low bone mass (BMD T-score lower than -2.0 in at least one location: Lumbar Spine, Femoral Neck or Total Hip sites) will receive study medication.~Primary outcome:~Total hip BMD change during a one-year treatment period.~Secondary outcome:~Change in Femoral neck BMD at 12 months, Bone turnover markers change over time (3, 9 and 12 month): C-terminal telopeptide of type I collagen (CTX), N-terminal propeptide of type I procollagen (P1NP).~Study population:~Thirty women between 20-70 years of age with spinal cord injury that occurred more than 24 month ago and low bone mass (BMD T-score lower than -2.0 in at least one location: Lumbar Spine, Femoral Neck or Total Hip sites)

This is a randomized study to determine the effects of monthly romosozumab for one year or one-time zoledronic acid on bone mineral density (BMD) and biochemical markers of bone formation and resorption, in patients with spinal cord injury (SCI) and low BMD.

This RCT was conducted to see effects of patient education manual on pain, ROM and functional performance in patient of knee osteoarthritis. In this study the investigators provide an educational manual as a home plan in which they educate and guide patients about proper posture, life style modification, precautions and safety measures and home exercise in patient with knee osteoarthritis.~The investigators will divide the patients in two groups. One group was treated with the patient education manual and routine physical therapy and the other group was treated with routine physical therapy alone. After baseline assessment patient was assessed at 2nd, 4th and 6th week and then do final assessment to analyse our results on SPSS, either patient education manual is helpful in minimising there pain functional limitation and increasing their Range Of Motion. Visual analogue scale, goniometry and WOMEC was used to measure outcome regarding pain, Range of motion and functional performance in patients with knee osteoarthritis. This study was help full in the management, to improve function and to decrease status of disability in future in patients with knee osteoarthritis.

This RCT was conducted to see effects of patient education manual on pain, ROM and functional performance in patient of knee osteoarthritis. In this study the investigators were provide an educational manual as a home plan in which the investigators educate and guide patients about proper posture, life style modification, precautions and safety measures and home exercise in patient with knee osteoarthritis

Anxiety disorders begin during childhood and adolescents, are extremely common, but are often under-diagnosed and under-treated. If untreated, pediatric anxiety disorders can be chronic and impairing into adulthood. The good news is that evidence-based treatments can be highly effective in reducing symptoms, and for a good number of children and adolescents, treatment can reduce anxiety symptoms to a minimum with marked improvement in function. In the largest comparative efficacy study, remission (minimal or no symptoms of anxiety), occurred in about 65% of children and adolescents treated with a combination of a selective serotonin reuptake inhibitor (SSRI) and cognitive behavioral therapy (CBT). In contrast, CBT without an SSRI achieved remission in 35% of children at 3 months and 45% at 6 months-a 30% and 20% difference, respectively.~Nonetheless, CBT alone is the preferred treatment of most patients and families. Lack of awareness of the significant difference in remission rates and concerns about medication side effects may drive patient and family preference, even though SSRIs have a positive safety profile.~In the study described above, CBT was limited in ways that might account for why it was less effective. CBT was shorter in duration, had fewer sessions, and less exposure opportunities than it was originally designed to have and had less family involvement than more current approaches. Given that patients and families prefer CBT, it is important to know if combination of CBT and an SSRI is truly superior to CBT only or whether fully implemented CBT can close the gap in remission rates with the combination of CBT and an SSRI. The study will also provide information about which children and adolescents achieve remission with CBT or CBT and an SSRI.~The Partners in Caring for Anxious Youth (PCAY) study will screen children and adolescents ages 7-17 years in pediatric primary care clinics affiliated with three institution: Lurie Children's Hospital of Chicago, University of California Los Angeles and University of Cincinnati. If a child screens positive with symptoms of an anxiety disorder, the patient and family will be offered an opportunity to learn about PCAY. If the family is interested in PCAY, a study staff person will provide information and answer any questions. If the patient and family want to enroll they will sign a consent form, complete an evaluation, and if eligible and willing to move forward, be randomized to either CBT or CBT plus an SSRI. The study team will work with the patient and family to connect to a therapist in the community to start CBT and if medication is part of treatment, work with the patient's pediatrician to begin medication. CBT will include up to 20 session of therapy and medication treatment will be a selective serotonin reuptake inhibitor (either fluoxetine, sertraline or escitalopram). The goal of treatment is for the child or adolescent with an anxiety disorder to reach remission and have a marked improvement in functioning. The first part of treatment lasts 6 months and there is then ongoing follow-up for an additional 6 months (12 months total). When the study is finished, the investigators hope to know if CBT and an SSRI is really superior to fully implemented CBT or not. The results of this study will inform patients, families, providers, payors and policy makers on the value of medication when combined with CBT.

Pediatric onset anxiety disorders (generalized anxiety, social anxiety, separation anxiety) are highly prevalent, and if untreated, are impairing into adolescence and adulthood. In the largest comparative efficacy study remission occurred in about 65% of children and adolescents treated with a combination of a selective serotonin reuptake inhibitors (SSRI) and cognitive behavioral therapy (CBT). In contrast, CBT without an SSRI achieved remission in 35% of children at 3 months and 45% at 6 months-a 30% and 20% difference, respectively. Despite the difference in remission rates, CBT alone is the preferred treatment of most patients and families. Lack of awareness of the significant difference in remission rates and concerns about medication side effects may drive patient and family preference even though SSRIs have a positive safety profile.~Critiques of CBT in the above study suggest that CBT was not as effective as it could be due to short treatment duration, restricted family involvement and limited exposure sessions. Would the combination of CBT and an SSRI still be superior to CBT only, if CBT was of longer duration, and included more family involvement and exposure sessions?~In the Partners in Care for Anxious Youth (PCAY) study, children and adolescents with an anxiety disorder ages 7-17 years followed in pediatric primary care clinics affiliated with three institution: Lurie Children's Hospital of Chicago, University of California Los Angeles and University of Cincinnati will be randomized to one of two treatment arms; either CBT only or CBT combined with an SSRI (either fluoxetine, sertraline, or escitalopram). CBT in PCAY will be 6 months in duration and include more family involvement, and more exposure opportunities than past trials. The 6-month acute treatment phase will be followed by 6 months of followup. The primary outcome will be anxiety symptom remission and reduction in impairment over 6 and 12-months.

Ribose has been shown to be very helpful in CFS and fibromyalgia. Many studies have also shown benefit for the symptoms of these conditions from Ashwagandha, Rhodiola, Schisandra, licorice, and green tea extract. The study is undertaken as an early open label study to check for the efficacy of a proprietary combination of these

Is a combination of Ribose, Ashwagandha, Rhodiola, Schisandra, licorice, and green tea extract helpful in CFS and FIbromyalgia?

Endoscopic methods are frequently used in the diagnosis of gastrointestinal system pathologies in children. In the investigators' center, which is a pandemic hospital, only emergency endoscopic procedures were performed during the pandemic period, while emergency and elective endoscopic procedures are performed in accordance with the recommendations of the Ministry of Health during the normalization process. Staff and patients in endoscopy units are at risk for COVID-19 infection by inhalation of airborne droplets, conjunctival contact, and potential fecal-oral contamination. In order to reduce the risk of contamination, according to the recommendations of the European Gastrointestinal Endoscopy Association (ESGE); proper cleaning of endoscopic devices, non-reuse of disposable devices, cleaning the endoscopy hall with a disinfectant solution, use of gowns FFP2 / 3 masks and jewelry during the procedure, handwashing with soap and hand disinfection is recommended before and after each procedure. In addition, it is recommended that patients who have undergone endoscopic procedures should be followed up or communicated on days 7 and 14 in terms of the development of COVID-19 infection.~It is recommended that patients should be questioned in terms of COVID-19 infection before endoscopy, but rapid antigen testing and serology are not routinely recommended. Molecular diagnosis (PCR, amplification) tests are recommended for patients at risk for COVID-19 infection.

Endoscopic methods are frequently used in the diagnosis of gastrointestinal system pathologies in children.

This is a first-in-human, randomized, double-blind, parallel-group, vehicle-controlled study to evaluate the efficacy, safety, tolerability, and PK of ATI-1777 solution following twice-daily applications to target areas of patients with moderate or severe atopic dermatitis (AD).~Patients will undergo screening evaluations to determine eligibility up to 30 days prior to randomization. Patients who meet all the entry criteria will be randomized on Day 1 to active or vehicle treatment. Patients will apply study drug (ATI-1777 topical solution 2.0% w/w or vehicle) twice daily for 4 weeks with weekly study visits and will return 2 weeks after the last dose of study medication for a Post treatment Follow-up (PTFU) Visit. Adverse event (AE) collection, physical examinations, clinical disease assessments (Eczema Area and Severity Index [EASI], Investigator's Global Assessment [IGA], AD body surface area [BSA], Peak Pruritus Numerical Rating Scale [PP-NRS]), vital sign assessments, PK evaluations, and clinical laboratory evaluations will be performed as detailed in the Schedule of Events.

This is a first-in-human, randomized, double-blind, parallel-group, vehicle-controlled study to evaluate the efficacy, safety, tolerability, and PK of ATI-1777 solution following twice-daily applications to target areas of patients with moderate or severe atopic dermatitis.

Background:~Burden: COVID -19, first reported in Wuhan, China, strikes the world hard as a pandemic by spreading up to 213 countries. Bangladesh is also facing its havoc with the death of 3000 among 229,185 cases at its 141st day. Most are mild cases presenting with influenza-like illness with expected recovery. According to World Health Organization, the overall global case fatality rate is currently estimated to be 2.9%. However, patients having severe or critical illness presenting with severe respiratory distress, ARDS or shock suffer most with mortality of 49.0-61.5%. Studies suggest that there are mild or severe cytokine storms in severe patients, which is an important cause of death. An exaggerated and uncontrolled release of proinflammatory mediators by an overly activated immune system is termed as cytokine storm (CS). Studies depicting that there might be an important relationship between SARS-CoV-2 and gut microbiota, as a marker to predict ARDS, can corroborate with the disease severity and outcomes of COVID-19.~Knowledge gap: Cytokine storm (CS) has an important role in the hemodynamic insults seen in very ill COVID-19 patients. In Bangladesh, no study has been conducted to evaluate the level of cytokines and the gut microbiota in COVID-19 patients presenting with different level of severity and their possible correlation with COVID-19.~Relevance: It will explore the role of CS and gut microbiota in COVID-19 illness severity. Thus, the results of the study will improve our knowledge and understanding of the problem, and thereby finding their solutions.~Objectives:~To estimate the burden of 'Cytokine Storm' and its correlation with the magnitude of the severity of COVID-19 illness in Bangladeshi adults.~Methods:~This will be a prospective observational study in adults aged ≥18 years old with COVID-19 having mild /moderate/severe/critical symptoms. The investigators will measure their cytokine (IL 6, TNF-Alpha, and IL1 Beta) levels and investigate gut microbiota in addition to regular laboratory tests at different time points of illness.

COVID -19, first reported in Wuhan, China, strikes the world hard as a pandemic by spreading up to 213 countries. Bangladesh is also facing its havoc with the death of 3000 among 229,185 cases at its 141st day. Most are mild cases presenting with influenza-like illness with expected recovery. According to World Health Organization, the overall global case fatality rate is currently estimated to be 2.9%. However, patients having severe or critical illness presenting with severe respiratory distress, ARDS or shock suffer most with mortality rates of 49.0-61.5%. Studies suggest that there are mild or severe cytokine storms in severe patients, which is an important cause of death. An exaggerated and uncontrolled release of pro-inflammatory mediators by an overly activated immune system is known as cytokine storms (CS) or cytokine release syndrome (CRS) which has an important role in the hemodynamic insults seen in very ill COVID-19 patients. This aberrant release of pro-inflammatory cytokines causes lung damage, myocarditis, acute kidney injury, etc. In this study, the investigators aim to estimate the burden of cytokines and their correlation with the magnitude of the severity of COVID-19 illness in Bangladeshi adults.

Irritable bowel syndrome (IBS) is a prevalent functional bowel disorder in which recurrent abdominal pain is associated with defecation and altered bowel habits. Although the pathophysiology is incompletely understood, it is generally regarded as a multifactorial disorder involving host factors such as low-grade immune activation, altered intestinal barrier function and defense. Environmental factors, including diet, are also suggested to play a role. Dairy products such as cow's milk are widely produced and an important component of the human diet. Cow's milk is composed of various macronutrients, micronutrients and water. Beta-casein is a major protein component of cow's milk; most cows produce a mixture of A1 and A2 beta-casein (conventional milk), whereas some cows produce only A2 beta-casein (A2 milk). It has been suggested that specific components in cow's milk, such as A1 beta-casein, may trigger gastrointestinal symptoms after intake.~The purpose of this randomized, double-blind, cross-over study performed in Maastricht University Medical Center (MUMC+) is to explore the acute and mid-terms effects of A2 milk versus conventional milk on gastrointestinal symptoms and immune and defense markers in separate groups of patient with constipation-predominant IBS and in patients with diarrhea-predominant IBS.

This aim of this study is to evaluate the acute and mid-term effects of A2 milk versus conventional milk on gastrointestinal symptoms in patients with constipation-predominant IBS and in patients with diarrhea-predominant IBS. Moreover, the effect of immune and defense markers will be studied.

Management of patients with SARS-CoV-2 presents a great challenge in the ongoing pandemic. The inflammatory reaction, evident in the later stages of the disease, is linked with high mortality rates. Pharmaceutical interventions at this stage often do not achieve the desired effects. Low Dose Radiation Therapy (LD-RT) has been utilized for treatment of inflammatory conditions because of its immunomodulatory effects. Thus, LD-RT may be an option in SARS-CoV-2 based on pre-clinical models and early clinical data. This study is to analyse the efficacy of LD-RT for treatment of Severe-Acute-Respiratory-Syndrome-Coronavirus-2 (SARS-CoV-2).

This study is to analyse the efficacy of LD-RT for treatment of Severe-Acute-Respiratory-Syndrome-Coronavirus-2 (SARS-CoV-2).

EVA4YOU is a cross-sectional study enrolling 3000 students and apprentices aged between 14 and 19 years. Examinations are conducted at schools and companies throughout Tyrol, Austria and include laboratory measurements; standardized medical interviews; anthropometry; liver elastography; ultrasonography of the carotid artery and the aorta, and blood pressure, bioelectrical impedance; visceral abdominal fat-tissue-thickness measurement, pulse-wave velocity measurements.~The study hypothesis is that the cardiovascular risk factors measured already influence the formation of atherosclerosis (measured as carotid and aortic Intima-Media Thickness and Pulse-Wave-Velocity) in adolescents.~A long-term follow-up by means of record linkage is furthermore planned to evaluate the effect of early atherosclerosis and the cardiovascular risk profile on future morbidity with a special focus cardio- and cerebrovascular events.

This is a single-center observational study on adolescents to determine predictors of the early steps of the formation of atherosclerosis and to quantify their influence on Intima-Media-Thickness of the carotid artery and the aorta and on the Pulse-Wave Velocity.~A long-term follow-up by means of record linkage is furthermore planned to evaluate the effect of early atherosclerosis and the cardiovascular risk profile on future morbidity with a special focus cardio- and cerebrovascular events.

Background This research is designed through randomization, control, and double-blind trial to explore the clinical effectiveness of intravenous laser irradiation of blood for knee degenerative arthritis; and to explore the changes in body's balance function. Furthermore to establish a new way of clinical rehabilitation therapy. The research will further study the special expression of blood cells after the treatment and as well as the molecular mechanism of low-energy intravenous laser therapy on hematopoietic stem cells. fold of the sun. The light accelerates blood and cells circulation in the human body, so that protein molecular structure would promote changes. Pain control is indicated in such treatment, but still lacking evidence of improving the symptoms of degenerative knee arthritis.~Purpose This research is designed through randomization, control, and double-blind trial to explore the clinical effectiveness of intravenous laser irradiation of blood for knee degenerative arthritis; and to explore the changes in body's balance function. Furthermore to establish a new way of clinical rehabilitation therapy. The research will further study the special biomarker to investigate the mechanism of low-energy intravenous laser therapy for osteoarthritis.~Method The investigators plan to recruit 20 patients who are between the ages of 50 to 75 years old, but younger than 75 years old. The participants are required to have clear conscious and be able to communicate. Their symptoms of degenerative arthritis could be one or both knees which last more than six months; with knee pain greater than 4 points when walking. The treatment group will receive an intravenous helium-neon laser phototherapy. A vein indwelling needle will be placed in their veins located in the upper elbow, and the laser fiber catheter will be introduced through the indwelling cannula. The power is set between 2.5 ~ 3.0Mw, 60 minutes each time, once a day for five consecutive days. The steps for the control group are the same, except that the output power is adjusted to zero intensity. This plan will be explained to the patient in detail during the outpatient visit and patients will sign the consent form upon agreement. Before intravenous laser irradiation, three days, one month, and three months after the therapy, 20 ml of autologous peripheral venous blood need to be drawn for basic blood tests and biomarker tests. At the same time, the clinical functions of patients will be evaluated, including visual analogous scale, Lequesne 's severity index, WOMAC scale, and balance function test.

This research is designed through randomization, control, and double-blind trial to explore the clinical effectiveness of intravenous laser irradiation of blood for knee degenerative arthritis; and to explore the changes in body's balance function. Furthermore to establish a new way of clinical rehabilitation therapy. The research will further study the special biomarker to investigate the mechanism of low-energy intravenous laser therapy for osteoarthritis.

Bronchiolitis is common infection in the small airways of the lungs in the pediatric population. It typically affects children under the age of two years during the fall and winter months.Infants with this condition often have a significant amount of nasal drainage and congestion. Infants are known to be obligate nasal breathers. When the nasal secretions block the nasal airway, then breathing, sleeping, and eating/drinking all become very difficult. For this reason it is very important to have a good method of suctioning out the nose and clearing out the secretions. Historically a baby's nose was suctioned with a bulb syringe. These are still commonly used and are given out in the hospital setting, although there are many other types of devices that have been developed recently that are used for suctioning. One of these devices that has become very common among parents now is called the NoseFrida. It is important to evaluate this device and its efficacy compared to the bulb syringe.~This research study will evaluate the difference in effectiveness of nasal suction between two different suction devices (NoseFrida and bulb syringe) in infants that have bronchiolitis. Bronchiolitis (a virus infection that goes into the lungs, which subsequently causes difficulty breathing, difficulty sleeping, and difficulty eating and drinking in children) is a common infection in young children. Patients will be considered for enrollment in the study based on inclusion/exclusion criteria. The patient's caregiver will be supplied with an information sheet, and any questions will be addressed. Those who verbally consent will be enrolled in the study. After parents or guardians (caregivers) provide informed consent for their child, researchers will review the child's medical record for information regarding their history of respiratory distress. The caregiver will then be supplied with both suction devices to be used once they are discharged home: The participants will be asked to use either a NoseFrida device or a bulb syringe first, and then to alternate thereafter. The device supplied which is instructed to be used first will be dependent on the week of enrollment in the study (we will rotate supplying NoseFrida to all patients asking participants to use NoseFrida first one week, and bulb syringe to all patients first the next week in order to attain similar size cohorts). Education will be given on how to use their respective the suction device devices. Along with the device, a form (Home monitoring form) will be supplied that will outline what should be monitored while using the device, including: number of days after discharge until respiratory symptoms resolve, number of days until the infant is eating/drinking well, and the number of days until the infant is sleeping well. A REDCAP survey will be emailed to participants after 5 days post discharge.

This research study will evaluate the difference in effectiveness of nasal suction between two different suction devices (NoseFrida and bulb syringe) in infants that have bronchiolitis. Bronchiolitis (a virus infection that goes into the lungs, which subsequently causes difficulty breathing, difficulty sleeping, and difficulty eating and drinking in children) is a common infection in young children. The caregiver-participants will be supplied with two suction devices (NoseFrida and bulb syringe suction). The devices should be used to clear nasal secretions as needed following discharge from the Emergency Center. The participants will be asked to use either a NoseFrida device or a bulb syringe first, and then to alternate thereafter. Caregivers will monitor how well their baby is breathing, eating/drinking, sleeping and how many times the baby has been seen by a medical provider in the 5 days post discharge from the Emergency Center. Post discharge, caregivers will complete a REDCAP survey asking questions about how their baby has been doing over the first 5 days following hospital discharge. This completes study involvement.

Hip arthroscopy for treatment of femoroacetabular impingement syndrome (FAIS) involves reshaping of the osseous sources of impingement (osteoplasty) and treatment of impingement-associated labral tears with labral repair. The hip joint is subluxated with traction to accomplish this procedure. The diagnoses of FAIS and the incidence of hip arthroscopy have both increased dramatically in the last 20 years in the US -- in a recent study using IBM Marketscan to evaluate rates of hip arthroscopic treatment of FAIS, the investigators found this incidence doubled from 1.2 to 2.1 per 100,000 person-years in just a 3-year period. Despite the increasing incidence of hip arthroscopy in the US, on a recent review the investigators have found few evidence-based studies on postoperative care. A particular area of debate is the use of postoperative hip braces. Postoperative hip braces are advocated to decrease postoperative pain by offloading hip musculature. They may also prevent overuse of the hip flexors by supporting the hip during gait. However there are no studies looking at efficacy of hip braces after hip arthroscopy, and on average 50% of high-volume hip arthroscopists use bracing. The utility of bracing is important because hip braces are expensive (averaging $350-$600): if there are over 7000 hip arthroscopies performed nationwide and 50% of surgeons use hip braces, this amounts to over $2,000,000. The investigator's overall objective is to use a randomized controlled trial to test the cited benefits of postoperative hip bracing on short term patient reported pain scores, validated hip-specific pain scores, and physical exam findings of hip flexor tendonitis.

Hip arthroscopy for treatment of femoroacetabular impingement syndrome (FAIS) involves reshaping of the osseous sources of impingement (osteoplasty) and treatment of impingement-associated labral tears with labral repair. Postoperative hip braces are advocated to decrease postoperative pain by offloading hip musculature. However there are no studies looking at efficacy of hip braces after hip arthroscopy, and on average 50% of high-volume hip arthroscopists use bracing. The objective of this study is to use a randomized controlled trial to test the cited benefits of postoperative hip bracing on short term patient reported pain scores, validated hip-specific pain scores, and physical exam findings of hip flexor tendonitis.

MS (Multiple Sclerosis) is the most common neurological disease involving disabilities in young adults, with Central Nervous System involvement in both the brain and spinal cord. In a recent review, its incidence in the United Kingdom is estimated at 7 new cases per 100,00 inhabitants per year, with a prevalence of about 100,000 patients. Bowel symptoms, in particular constipation and faecal incontinence, affect more than two thirds of MS patients, and have a significant impact on patients' quality of life (QoL) by significantly limiting their social, occupational and emotional life.~Recently, bowel management based on Transanal Irrigation (TAI) has also been proposed in patients with MS, but TAI efficacy on intestinal transit time and patient's compliance with TAI have not been defined yet.~The primary objective of the study is to assess the prevalence, characteristics, severity and impact on the Quality of Life of intestinal disorders in patients who consecutively refer to the neurological clinic for the diagnosis and treatment of Multiple Sclerosis at Ferrara University Hospital, Italy.~Secondary objectives are to correlate the severity and characteristics of constipation and fecal incontinence with intestinal transit time and the type of faeces evacuated according to the Bristol Stool Form Scale; to evaluate the costs in terms of the precautions (diapers, traverses, drugs, medicated clysms, etc.) and the time dedicated to the evacuation, and how these items change in relation to the use of TAI; and finally, to study the composition of the intestinal microbiota in MS patients in relation to the type of bowel characteristics, comparing it with the profile of the healthy population of the same region of origin, Emilia-Romagna, Italy.~The study proposed is a monocentric prospective observational study. The study population will be composed of patients who will consecutively refer to the Neurological Clinics of the University Hospital of Ferrara, Italy for a number of about 150 patients.~The study will consist of two phases.The first phase will be the selection of eligible patients by administering two self-filling questionnaires: PacQol (Patient Assessment of Constipation Quality of Life) and NBD (Neurogenic Bowel Dysfunction Score).~Patients with PacQol score ≥ 32 will be sent to the surgical clinic for the second phase. During the latter phase, patients will undergo a number of visits varying from 1 to 4 depending on the patient's willingness to continue the study. After the illustration of the purpose and protocol of the study to the patient, classification of constipation and/or faecal incontinence in accordance with the Rome III Diagnostic Criteria will be assessed, with consideration of other possible etiopathogenetic factors other than MS. Further questionnaires will be filled in to evaluate the disease status (Constipation scoring system by Agachan-Wexner, Obstructed defecation score by Altomare, Fecal Incontinente grading scale by Jorge-Wexner); if the patient will consent to the continuation of the study, he will be given 7-days food diaries, evacuation diaries, radiopaque markers, stool collection container and appointment date for plain abdominal X-ray which may coincide with the appointment for examination number 2 (visit 2 or 3).~In particular, radiopaque markers Intestinal Transit Study will be performed according to the Bouchoucha procedure revised by Abrahamsson, which involves ingestion of 10 markers for 6 days at the same time and execution of a plain abdominal X-ray on the 7th day. During this week the patient will complete an evacuation diary recording the time and number of evacuations, the method of eventual bowel care, the consistency of faeces according to the Bristol Scale, any episode of fecal incontinence, the type of hygiene measures in general, the number of enemas, diapers, and any other garrison used in relation to the evacuation.~Patients will be asked to collect a faecal sample in a container during the last week before the following inspection at Visit 2.~During the second visit, the outcome of the plain abdominal X-ray will be discussed, the completed diaries will be collected, and the faecal sample will be stored at -20 C° and subsequentely sent to the Laboratory of the Department of Pharmacy and Biotechnology of the University of Bologna, Italy for the analysis of the intestinal microbiome composition.~Patients with severe NBD impairment will be offered the adoption of TAI as a way to manage their own evacuation, replacing any other measure used until that moment (suppositoires, enemas) with the exception of the possible intake of macrogols and/or prebiotics and/or probiotics which instead can be continued. This treatment will be proposed to all patients with severe impairment of intestinal function.~The TAI training with Peristeen will be carried out at the surgical clinic of the Surgical Department of the Ferrara University Hospital, Italy, by the personnel involved in the study, usually in a single session, but more sessions may be necessary.~During the following 4 weeks, patients will continue to use the Peristeen at home according to the instructions provided by the training staff collecting a stool sample each week. During the last of the four weeks of TAI use patients will repeat the compilation of food diaries, evacuation diaries, the radiopaque markers Transit Time, and collection of the stool for microbiota analysis. The appointment for the radiography could coincide also in this case with the following visit (visit 3 or 4).~During the last visit the outcome of Transit Time X-ray will be discussed, completed diaries and stool samples will be collected, and PAC-QoL questionnaire will be submitted to patients who completed the study pathway.~Patients will be asked about overall satisfaction of TAI treatment with Peristeen by means of a numerical assessment from 0 to 10.~Finally, any comment will be noted as well any events that might be related to TAI irrigation with Peristeen will be recorded.~Patients will undergo a neurological examination 3 months after the start of treatment.~The whole duration of the study will be of 2 years.

MS (Multiple Sclerosis) is the most common neurological disease involving disabilities in young adults, with bowel symptoms, in particular constipation and fecal incontinence. The main objectives of the study are to assess the prevalence, characteristics, severity and impact on the Quality of Life of intestinal disorders in this population, to correlate the severity and characteristics of constipation and fecal incontinence with Intestinal Transit Time and the time dedicated to the evacuation, and how these items change in relation to the use of transanal irrigation (TAI). Another objective is to identify the composition of the intestinal microbiota in MS patients in relation to the type of bowel characteristics, comparing it with microbiota profile of the healthy population of the same region of origin, Emilia-Romagna, Italy.

All study participants had blood in the morning on fasting after 8-12 hours of fasting from the cubital vein. Determination of the level of cytokines TNF-α, IL-1β, IL-4 and IL-10 (pg/ml) in blood serum by enzyme-linked immunosorbent assay (ELISA).~Sample preparation: before testing, 1 part of the plasma is diluted 30-50 times with Tris buffer, depending on the test system and the kit manufacturer's instructions.~Definition progress:~preparation of microtiter strips;~add the material diluted with buffer to the well of the microtiter strip and incubate for 1 hour at room temperature;~washing;~add immunoconjugates to the well of the microtiter strip and incubate for 1 hour at room temperature;~washing;~add the o-phenyldiamine / H2O2 substrate solution;~after exactly 3 minutes of hydrochloric acid (1 mol / l);~reading the results on an ELISA analyzer after 10-120 minutes. 2.4. Collection of blood samples to determine the level of uric acid All participants in the study had blood drawn in the morning on fasting after 8-12 hours of fasting from the cubital vein. The level of uric acid was determined on the CYAN Start apparatus using a unified method.~2.5. Method for determining anxiety-depressive syndrome. When examining patients with unstable angina pectoris were used: Hospital scale [Kozlova S.N. 2013]. And also the Spielberger-Khanin scale [Psychiatry - Hoffman A.G. 2010], developed by Spielberger Ch.D. and adapted by Yu.L. Khanin. to assess cognitive functions [Psychiatry - Gofman A.G. 2010].~Description of the hospital scale This questionnaire is intended for self-completion by the patient [Kozlova S.N. 2013]. The questionnaire consists of 14 statements, serving 2 subscales: the subscale alarm marked in red, consists of odd items - 1, 3, 5, 7, 9, 11, 13 and the subscale depression marked in blue consists of even items - 2, 4, 6, 8, 10, 12, 14.~Each statement corresponds to 4 answer options, reflecting gradations of the severity of the sign and coded according to the increase in the severity of the symptom from 0 (no) to 3 (maximum severity). The final scores for the two subscales are obtained by summing the numerical values of the answers. When interpreting the results, the total indicator for each subscale is taken into account, while there are 3 areas of its values:~0-7 - normal (no reliably pronounced symptoms of anxiety and depression);~8-10 - subclinical anxiety and / or depression;~11 and above - clinically significant anxiety and / or depression. The filling of the scale was carried out by patients under standard conditions, after a short instruction for filling, within a clear time frame.~Description of the Spielberger-Hanin scale The Spielberger Anxiety Scale is an informative way to self-assess the level of anxiety at a given moment (reactive anxiety as a state) and personal anxiety (as a stable characteristic of a person). Developed by Ch.D.Spielberger and adapted by Yu.L. Khanin [Psychiatry - Gofman A.G. 2010].~This scale consists of two subscales: judgments from 1 to 20 determine the presence of situational anxiety, judgments from 21 to 40 determine the presence of personal anxiety.~When analyzing the results of self-assessment, it should be borne in mind that the overall final indicator for each of the subscales can range from 20 to 80 points. Moreover, the higher the final indicator, the higher the level of anxiety (situational or personal).~When interpreting indicators, you can use the following rough estimates of anxiety:~up to 40 points - low,~41 - 54 points - moderate;~55 and more - high. 2.6. Treatment All patients with unstable angina pectoris offer conventional therapy, which includes intravenous infusion of nitrates for 12-24 hours, followed by prolonged nitrates, beta-blockers, ACE inhibitors or sartans, antiplatelet agents, anticoagulants, clopidogrel, statins. Patients have elevated levels of uric acid according to the traditional immedia Febuxostat (not a purine blocker of xanthine oxide, manufactured by Berlin Chemie, Germany) at a dose of 0.04-0.08 g / day per day. Patients who had anxiety-depressive syndrome Divase syndrome (antibodies to the brain-specific protein S-100, manufacturer MATERIA MEDICA HOLDING, LLC (Russia)) in a fixed dose of 0.6 mg / day, which has a neurotropic and antioxidant effect.

Introduction:~Today it is necessary to emphasize that coronary heart disease is often associated with anxiety disorders. Research over the years has shown several and sometimes surprising links between coronary heart disease and mental illness, and has even suggested that both of these phenomena may actually cause each other. However, the exact nature of these links has not yet been clearly established.~Methods: The study included 202 patients with coronary artery disease, of whom 42 patients were with stable angina pectoris, they participated as a control group, and 160 patients with unstable angina pectoris, who made up the main group.~Among them there are 102 women and 100 men between the ages of 30 and 88. The average age was 63.75 ± 11.37 years.~All study participants had blood in the morning on fasting after 8-12 hours of fasting from the cubital vein. Determination of the level of cytokines TNF-α, IL-1β, IL-4 and IL-10 in blood serum by enzyme-linked immunosorbent assay (ELISA).~All participants in the study had blood drawn in the morning on fasting after 8-12 hours of fasting from the cubital vein. The level of uric acid was determined on the CYAN Start apparatus using a unified method.~When examining patients with unstable angina pectoris were used: hospital anxiety and depression scale [Kozlova S.N. 2013]. And also the Spielberger-Khanin scale [Psychiatry - Hoffman A.G. 2010], developed by Spielberger Ch.D. and adapted by Yu.L. Khanin. to assess cognitive functions [Psychiatry - Gofman A.G. 2010].

In the field of soft tissue sarcomas, Gastrointestinal Stromal Tumors (GIST) represents a really peculiar neoplasm for its biological and clinical properties. Surgery (if feasible) is the main therapeutic approach for all the patients with localized disease, while a pharmacological adjuvant treatment is reserved to those with a relevant risk of recurrence/progression.~After tumor removal, clinical and radiological follow-up is of central importance to early intercept recurrence and to evaluate the most correct subsequent therapeutic approach. In particular, for the group of patients with GIST at very-low and low risk of recurrence/progression, the evidences to support a specific follow-up program and its features are poor.~On the basis of the aforementioned considerations, we propose a multi-institutional retrospective study in order to identify the most relevant and advisable features of follow-up, and to explore its impact on principal clinical outcomes. Moreover, a dedicated effort will be pursued to identify the peculiar characteristics (if any) of patients that experienced recurrence of the disease.~The study will collect data about patients affected by primary GIST at very-low and low risk of recurrence/progression, referred to participating Institutions between January 2000 and February 2020

This is a multi-institutional retrospective study in order to identify the most relevant and advisable features of follow-up, and to explore its impact on principal clinical outcomes. Moreover, a dedicated effort will be pursued to identify the peculiar characteristics (if any) of patients that experienced recurrence of the disease.~The study will collect data about patients affected by primary GIST at very-low and low risk of recurrence/progression, referred to participating Institutions between January 2000 and February 2020

This is a Phase II study to evaluate the efficacy and safety of TACE combined with sorafenib and tislelizumab in patients with advanced HCC.~30 subjects with advanced HCC (Barcelona-Clinic- Liver-Cancer [BCLC] stage C, or China liver cancer staging [CNLC] IIIa and IIIb) will be enrolled in the study.~Both sorafenib (400mg P.O. Bid) and tislelizumab (200mg I.V. q3w) will be started at 3-7 days after the first TACE. TACE will be repeated if clinically indicated based on the evaluation of follow-up laboratory and imaging examination. Sorafenib will last until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first. Sorafenib administration will be delayed in cases of grade ≥2 hand-foot syndrome, grade >3 hematologic toxicities or grade ≥3 hypertension. After recovery, sorafenib will be reintroduced at a reduced dose according the sorafenib dose delay and reduction guidelines. Treatment of tislelizumab will last up to 24 months, or until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first. Patients will be allowed to have sorafenib or tislelizumab as a sigle agent and will be still considered on study when the other drug cause intolerable toxicity.

This study will evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with sorafenib and tislelizumab in patients with advanced hepatocellullar carcinoma (HCC).

This is a Phase II study to evaluate the efficacy and safety of TACE combined with lenvatinib and sintilimab in patients with advanced HCC.~30 subjects with advanced HCC (Barcelona-Clinic- Liver-Cancer [BCLC] stage C, or China liver cancer staging [CNLC] IIIa and IIIb) will be enrolled in the study.~Lenvatinib 12mg (body weight ≥60kg) or 8mg (body weight <60kg) P.O. qd and sintilimab (200mg I.V. q3w) will be started at 3-7 days after the first TACE. TACE will be repeated if clinically indicated based on the evaluation of follow-up laboratory and imaging examination. Lenvatinib will last until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first. Sintilimab will last up to 24 months, or until disease progresses, intolerable toxicity, withdrawal of informed consent, loss of follow-up, death, or other circumstances that require termination of treatment, whichever occurs first. Patients will be allowed to have lenvatinib or sintilimab as a sigle agent and will be still considered on study when the other drug cause intolerable toxicity.

This study will evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined with lenvatinib and sintilimab in patients with unresectable advanced hepatocellullar carcinoma (HCC).

Pulmonary hypertension (PH) is a pathophysiological disorder hemodynamically characterized by increased pulmonary vascular resistance and pressure. This can lead to right ventricle pressure overload and failure which is worsened by cardiopulmonary bypass (CPB) and extracorporeal circulation and is accompanied by high rates of morbidity and mortality in cardiac surgery patients. Pharmacological agents used to decrease pulmonary vascular resistance and right ventricle afterload are prostaglandins, iloprost, milrinone, nitric oxide (NO) and recently Levosimendan. These agents can be administered intravenously or via inhalation.~In this study, Levosimendan will be administered in patients with pulmonary hypertension undergoing cardiac surgery. The aim of the study is to examine the pharmacokinetics and pharmacodynamic properties of Levosimendan in cardiac surgery patients with pulmonary hypertension and impaired right ventricular function. The drug will be administered in different doses to define the dose at which Levosimendan administration reduces pulmonary vascular resistance and pressure without causing significant reduction of systemic vascular resistance and pressure. The anti-inflammatory effect of the perioperative use of Levosimendan in cardiac surgery will also be studied.~In this setting, 45 patients with PH caused by left sided heart disease, will be assigned into three groups:~GROUP A: Administration of Levosimendan at a dosage of 3mcg/kg after anesthesia induction.~GROUP B: Administration of Levosimendan at a dosage of 6mcg/kg after anesthesia induction.~GROUP C: Administration of Levosimendan at a dosage of 12mcg/kg after anesthesia induction.~Before and after the administration of the drug, heart function will be evaluated by hemodynamic measurements obtained by the Swan-Ganz catheter. These parameters will be heart rate (HR), blood pressure (BP), mean pulmonary arterial pressure (MPAP), central venous pressure (CVP), cardiac output (CO), pulmonary capillary wedge pressure (PCWP), cardiac index (CI), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR). Transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE) will also be used. The anti-inflammatory action of Levosimendan will also be evaluated by interleukin-6 (IL-6) measurements.~This study will lead to conclusions regarding the effectiveness of Levosimendan administration in the treatment of right heart failure and PH in cardiac surgery patients.

The aim of the study is to examine the pharmacokinetics and pharmacodynamic properties of Levosimendan in cardiac surgery patients with pulmonary hypertension and impaired right ventricular function.

Protocol PTR-01-002 is a 3-part Phase 2, open-label study of PTR-01. While new patients will be enrolled, priority will be given to patients that satisfactorily completed study PTR-01-001.~In Part 1, patients will receive a dose of 3.0 mg/kg every week for a total of 4 doses. This will be followed by Part 2 in which patients will receive a dose of 3.0 mg/kg every other week for a total of 7 doses. In Part 3, patients will be followed for 12 weeks. No investigational therapy will be administered during this time. At the end of each dosing period, an efficacy assessment will be performed. Safety will be assessed continuously throughout the study.~Following the end of Part 3, patients may be eligible for a potential long-term extension to further refine the dosing regimen, depending upon study drug availability.

Protocol PTR-01-002 is a 3-part Phase 2, open-label study of PTR-01. While new patients will be enrolled, priority will be given to patients that satisfactorily completed study PTR-01-001.

The Sahara Study is intended to evaluate the safety and effectiveness of the N-SWEAT Patch for use in subjects with excessive axillary sweating, or primary focal axillary hyperhidrosis.~Safety of the N-SWEAT Patch will be confirmed by assessing the occurrence of local skin reactions, treatment-related adverse events (AEs) and Serious Adverse Events (SAEs).~Demonstration of effectiveness will be assessed by a significant improvement (reduction) in Hyperhidrosis Disease Severity Score (HDSS) in subjects treated with the N-SWEAT Patch. Secondary and additional endpoints based on complementary clinical instruments, including Quality of Life Measures (QOL) and Gravimetric Sweat Production GSP), have been included to further demonstrate performance.

The Sahara Study is a study to evaluate the safety and effectiveness of the N-SWEAT Patch for use in subjects with excessive axillary sweating, or primary focal axillary hyperhidrosis.

A human intervention study with healthy volunteers will be carried out to investigate the effects of partial replacement of red meat with legume-based foods on gut metabolism and markers for colorectal cancer as well as biomarkers for cardiovascular diseases and type 2 diabetes.~The study will be done in parallel-design, randomized fashion, with healthy male volunteers aged 20-65 years. Inclusion and exclusion criteria are described elsewhere. Duration of the intervention will be 6 weeks.~Intervention groups will be as follows (n=50/group):~Group 1: The habitual diet of participants is supplemented with 760 g of cooked and boneless red meat per week, representing the average meat consumption of Finnish men and supplying 25% of protein intake.~Group 2: The habitual diet of participants is supplemented with legume-based foods providing equal amount of protein as 560 g of red meat and 200 g of red meat per week.~The consumption of red meat and legumes will be kept stable throughout the intervention and participants are advised to avoid consuming any red meat or legumes in addition to those provided from the research center. The investigators also aim to investigate, whether replacing red meat with legumes induces other changes in diet. This information is be important if increasing legume consumption is recommended at the population level.~Before starting the intervention, participants will get dietary advice how to follow their diets. They will get the red meat and legume-based foods for free to help to implement the diets and to enhance compliance.~Blood, urine and fecal samples will be collected at the baseline and at the end of the intervention. Nutrient intake and food consumption during the intervention will be analyzed from 4-day food records at the baseline and at the end. Nutrient intakes will be calculated using a new Finnish 'Aromi' software.~The following data collection and analyses will be carried out at the baseline and at the end of the intervention period:~height, weight, waist and hip circumferences~body composition by bioelectrical impedance analysis~resting blood pressure~fasting lipid profile in the plasma (total cholesterol, LDL and HDL, triglycerides)~fasting glucose and insulin, HbA1c in the blood~high sensitive C-reactive protein~markers for nutritional status in plasma/serum: hemoglobin, transferrin receptor, ferritin, vitamin B12, folate, vitamin D~urea/nitrogen in the urine~total and heme-based N-nitroso compounds in feces, concentrations of bile acids, gut microbiota

The aim of this study is to investigate the effects of partial replacement of red meat with legume-based foods on gut metabolism and markers for colorectal cancer as well as markers for cardiovascular diseases and type 2 diabetes in healthy working age men. The study participants will be stratified into two groups with different amounts of red meat in diet: 1) a diet containing 760 g of cooked and boneless red meat, supplying 25% of daily protein intake and 2) a diet supplying 20% of protein intake with legume-based foods and 5% of protein intake with red meat. The participants will get all meat and and legume-based foods from the research center; otherwise they will be asked to follow their habitual diet. Blood, urine, and stool samples will be collected at the baseline and at the end of the 6 week intervention, as well as BMI, blood pressure and body composition. Nutrient intake and food consumption will be analyzed from 4-day food records at the baseline and at the end of the intervention period.

Due to medical progress and an aging population, the number of patients and caregivers who face the profound existential challenges of advanced incurable cancer is constantly growing. Clinically significant existential distress may result from a fear of suffering and perceived lack of control, fear and uncertainty about the end of life, feelings of burdensomeness or insufficiency, grief about missed opportunities, and profound loneliness. Such distress may have a unique and independent contribution to health care outcomes at the end of life. Despite an increasing interest in existential and palliative care interventions that discuss such issues openly, a lack of systematic quantitative data on existential distress and specific support needs hampers clinicians to consequently detect and address existential needs. This longitudinal study aims to 1) systematically investigate the frequency, longitudinal trajectory and predictive impact of existential distress on patient- and caregiver-relevant end-of-life outcomes and 2) determine patients' and caregivers' specific need for and utilization of psychosocial support with respect to existential concerns.~Adult patients diagnosed with advanced cancer and caregivers will be consecutively recruited from outpatient and inpatient treatment facilities of the Univer-sity Cancer Center Hamburg and affiliated clinics. Existential distress, end-of-life outcomes, and mental disorders in 1,000 participants (500 patients, 500 care-givers) will be assessed using self-report questionnaires at five points of assessment over a period of 12 months and diagnostic interviews (at baseline, after six months). To determine the prevalence of existential distress, mental disorders and palliative care outcomes descriptive statistics will be calculated. Descriptive analyses will also be used to examine the need for and utilization of psychosocial support. To investigate the predictive impact of existential distress and patient- and caregiver-relevant end-of-life outcomes multiple linear and logistic regression will be conducted. To analyze longitudinal trajectory of existential distress growth mixture models will be used.~Shaping a clear and systematic knowledge about frequent and persistent existential concerns that are most relevant to the risk for unfavorable end-of-life outcomes, results will significantly contribute to the recognition and manage-ment of existential distress and provide a valuable basis for the development of targeted interventions.

Despite the potential for alleviation of existential distress through psychosocial interventions, existential concerns and their impact on health care outcomes of patients and caregivers have not yet been systematically studied. The aim of this longitudinal cohort study is to investigate the frequency, longitudinal trajectory and predictive impact of existential distress on patient- and caregiver-relevant end-of-life outcomes. Further, it aims to determine the need for and utilization of psychosocial support in patients and caregivers with regard to existential concerns.

A precise reconstruction of the left atrium (LA), the pulmonary veins (PV) and the left atrial appendage (LAA) is of critical importance in order to achieve efficient and safe results in atrial fibrillation ablation. Currently the LA reconstruction methods are mainly based on techniques as Fast Anatomical Mapping (FAM) and cardiac CT merging. FAM mapping requires catheter manipulation by a skilled operator and it is time consuming. The raw anatomy obtained with FAM requires also a post imaging refinement of the LA surfaces by shaving of the image with sculpting tools before the initiation of the ablation and throughout the procedure. A drawback of this approach is represented by the frequent lack of accuracy in the definition of critical areas of the LA during the ablation as PV antrum, left PVs-LAA appendage ridge, PV carinas. An alternative approach is based on the merging of the FAM reconstruction to a CT scan of the left atrium acquired before the procedure (Carto Merge). The advantage of this technique is a far better definition of the LA anatomy including PV antrum, PV sizing, angle of insertion on the LA of the PV and the recognition of PV anomalies (PV common os, separated branches, additional PVs). The drawbacks of these approaches are mainly related to the exposure of the patients to contrast media during the cardiac CTA and the additional costs of the CT scan to the entire budget of the procedure.~The CARTOSOUND® FAM algorithm is a model-based algorithm, developed using the Machine Learning methodology, which reconstructs a 3D volume of the Left Atrium (LA) anatomies (LA Body, Left Atrial Appendage - LAA, Left Inferior Pulmonary Vein - LIPV, Left Superior Pulmonary Vein - LSPV, Right Superior Pulmonary Vein - RSPV, and Right Inferior Pulmonary Vein - RIPV) based on a series of 2D ultrasound frames acquired from the Right Atrium - RA (Fossa Ovalis) and the RVOT. In addition to the 3D volume reconstructed, the CARTOSOUND® FAM algorithm generates 2D automatic contours that are overlaid on the corresponding 2D ultrasound frames and provides auto segmentation of the Left Atrium (LA) anatomies. The advantages of the CARTOSOUND FAM are related to the shortening of mapping required to achieve an entire LA reconstruction and better resolution of the LA anatomy compared to FAM.~The aim of the present study is to compare the LA reconstruction obtained with CartoSound-FAM software and The M-FAM software to the Carto Merge 3D reconstruction and FAM in consecutive patients referred for AF ablation.

The aim of the present study is to compare the LA reconstruction obtained with CartoSound-FAM software and The M-FAM software to the Carto Merge 3D reconstruction and FAM in consecutive patients referred for AF ablation.

To evaluate the pharmacokinetic Interaction, safety and tolerability of the combination compared with the administration of AD-2101 and AD-2102.

The purpose of this study is to evaluate the Pharmacokinetic Interaction Between AD-2101 and AD-2102 in healthy male subjects.

This study aims to evaluate the safety and efficacy of Nerivio for the acute treatment of menstrual migraine (pure menstrual migraine or menstrually-related migraine).~Up to 500 US-based adults aged 18-55 years old who have been prescribed the Nerivio device and have used it at least 4 times between October 2019 and December 2020.~Informed consent must be obtained from the participant before any protocol-related activities are performed. The consent language will appear as the first page of the survey, and participants will click either agree or disagree to the consent statement; those who click agree will proceed to the survey, those who click disagree will be brought to an exit page.~Users of Nerivio whose details are in the sponsor's database will be contacted by email (provided by the patient during the sign-up process in the Nerivio app required to use the device) and/or through an app notification and will be asked to complete a 5-minute online survey assessing satisfaction, effectiveness, and safety. Participants will sign an informed consent form which will appear as the first page of the survey using open-ended questions, multiple choice questions and Likert scales. Participants will be directed to provide honest opinions regarding the device use for menstrual migraine. No additional information will be collected, and no medical records will be used in this investigation.

Post-marketing, retrospective, observational survey study. Users (menstruating women only) of Nerivio who have used Nerivio at least 4 times between October 2019 and December 2020 will be contacted by email and/or through an app notification and will be asked to complete a 5-minute online anonymous survey assessing satisfaction, effectiveness, and safety. Eligible users will sign an informed consent form (the consent language will appear as the first page of the survey, and participants will click either agree or disagree to the consent statement; those who click agree will proceed to the survey, those who click disagree will be brought to an exit page) and complete a survey asking about their satisfaction with Nerivio and the effectiveness and safety of the device for acute treatment of menstrual migraine. During the survey, participants will be screened to verify that they have menstrual migraine (self-reported) and have used Nerivio to treat menstrual migraines.

The safety and effectiveness of nProfiler® 1 Stomach Cancer Assay have been evaluated with stage II and III advanced gastric cancer patients based on the 6th of the American Joint Committee on Cancer (AJCC) through discovery clinical trial (418 patients) and confirmatory clinical trial (684 patients).~The goal of this study, a retrospective, multi-center, single-blind, pivotal trial, is to assess clinical equivalence with stage II and III advanced gastric cancer based on the 6th and 8th of the AJCC and to evaluate prognostic equivalence between surgery only group and adjuvant chemotherapy group in Low risk group.~The study will follow these procedures; Sample screening, Sample Preparation and Sample Criteria Evaluation, Sample enrollment, nProfiler® 1 Stomach Cancer Assay (gastric cancer prognosis prediction), Prognostic Result Report, and Evaluation of Clinical Performance.

A retrospective, multi-center, single-blind, pivotal trial to assess clinical equivalence with stage II and III advanced gastric cancer based on the 6th and 8th of the AJCC

Introduction~Obesity is one of the most important public health conditions worldwide. The morbidity can largely reduce life expectancy. Bariatric surgery for severe obesity is an effective treatment that results in the improvement and remission of many obesity-related comorbidities, cardiovascular benefits, as well as sustained weight loss and improvement in quality of life. Different surgical procedures for weight loss have been developed, with the most common ones being sleeve gastrectomy (SG) and Roux-en-Y Gastric Bypass (RYGB). RYGB is the most commonly used procedure for weight loss in Switzerland, even though in the last decades there has been a global shift towards SG. Independently from the applied procedure, bariatric surgery remains the most effective and durable intervention for obesity. Modern bariatric surgery has an excellent safety profile, even though complications in the short and long term have been reported. Extensive research also increased the understanding of the wide range of mechanisms underlying the effectiveness of bariatric surgery. The relative contributions of these mechanisms vary according to the chosen procedure, where altered satiety and hunger are considered important factors after RYGB. Other mechanisms have also been proposed, including changes in gut hormones, reduced appetite, increased satiation, increased energy expenditure, alteration in the gut microbiota and bile acids levels and composition, as well as changes in vagal nerve signalling. Changes in food preferences have also been implicated as an important candidate mechanism as patients prefer low-sugar low-fat food and report finding food, in general, less enjoyable after RYGB. Both humans and rats eat less and display altered food preferences after RYGB, but the underlying behavioural mechanism remains unclear.~The aim of public health policy in the treatment of obesity should be the development of effective prevention and better therapies which would eliminate the need for surgery altogether. Until then, bariatric surgery is safe, effective, affordable, and with large room for improvement. Furthermore, a deeper understanding of the physiological changes underlying the improvement of the morbidity may help in developing new therapies. So far, direct measurements of changes in food selection in humans after RYGB have been limited by the unreliability of patients, which poses significant methodological and conceptual challenges to researchers and study design . Self-monitoring requires time and effort, and many find tracking of dietary intake tedious, which contributes to attrition . Direct measurements, however, represent an essential component in the attempt to understand how RYGB alters eating and food preferences, but laboratory settings preclude a real-life environment. Consequently, obesity researchers have attempted to develop new easier tracking methods such as photography of food items to monitor dietary intake both in the clinical setting and everyday life. These new methods seem more effective compared to others. For instance, mobile phone applications of photographic food recognition (PFR) such as SNAQ enable patients to record and submit consumed food items, portion sizes and frequency of consumption during a pre-defined period. However, this technology is still in its infancy and assessment procedures need to be validated by trained professionals. The doubly labeled water (DLW) method has been proposed as a gold standard to assess free-living total energy expenditure and can be used to monitor the body composition (BC) and total energy expenditure (TEE) of an individual under circumstances of energy balance based on dilution equations of the labelled isotopic elements in the body . Direct segmental multifrequency bioelectrical impedance analysis (DSM-BIA) is considered a practical, non-invasive, and relatively inexpensive method to quickly assess the BC27 and the estimations of BC with DSM-BIA are reported to be consistent with those of the DLW method also for obese patients. The joint measurement of TEE using the estimations of the PFR and the DLW method would serve the validation of PFR for the measurement of TEE in patients undergoing RYGB. PFR would become then a powerful tool for research and provide useful information for the design of appropriate individualized obesity treatment programs.~Research question~The aim of this study is to investigate changes in food preferences, total energy intake of the three primary macronutrients and meal patterns between obese women (BMI ≥ 35) before and after Roux-en-Y gastric bypass and lean (BMI ≤ 25) and obese (BMI ≥ 35) controls by means of PFR with the mobile application SNAQ.~Methods~This will be a single-centre observational case-control prospective cohort study on female human subjects with morbid obesity, living in Switzerland and undergoing RYGB (n=20), obese controls (n=20), and lean controls (n=20) before, 3, 6, and 12 months after surgery and beginning of the study respectively. The optimal number of participants included can be based on power calculations with an equivalence design and on the hypothesis that patients will have similar caloric intake to the lean control group one year after RYGB. The equivalent caloric intake between the two groups is defined by an equivalence range of 210 kcal/day with a SD of ±200 kcal. For achieving a power of 90% and a p=0.05 in order to exclude a difference of means > 210 kcal/day, n=20 participants are required per group . Patients are enrolled in this study if (1) they are females aged ≥ 18 years, (2) have a body mass index (BMI) ≥ 35 kg/m2 without any previous bariatric surgery, (3) have a planned RYGB, (4) can move autonomously, (5) have a basic technological knowledge, (6) are fluent in German, and (7) are able to give their informed consent. Obese controls respect the same criteria, but have no plan to undergo surgery, which makes this group very hard to recruit. Lean controls have BMI ≤ 25 kg/m. The main purpose of the lean control group is to evaluate test stability over time and across multiple retesting. Patients who conform to the recruitment criteria are enrolled at the outpatient clinic of the University Hospital of Zurich. Obese and healthy controls are recruited by the study team. The study protocol is explained and written informed consent is obtained from all participants. The study protocol was approved by the Ethical Committee of the Canton of Zurich (BASEC-Nr. 2019-00952). TEE under free-living conditions is assessed using the DLW method. On the day before measurement, BIA is performed. On the first day of measurement, subjects perform urine collection at baseline and consume oral administration of DLW. After DLW administration, subjects collect urine respectively 3 and 4 h after administration and again after 7 days at the same time point of the second and third urine sampling . Subjects are instructed not to change their lifestyle or medication during the study period. Under free-living conditions for one week, overall dietary intake is registered by the participants using a mobile app for the photo-recognition of food items. Participants record their dietary intake over 7 days before, 3, 6, and 12 months after surgery.~Data analysis~The data of each patient will be organized as follows: time of the meal, total calories, total carbohydrates, proteins and fat, food group. This result has to be summed up for the final TEE calculation, in order to have the total amount of each variable per meal, per day and per week. The PFR data will be compared with DWL-based TEE for validation of the dietary assessment. Descriptive statistics will be used to describe demographic data, as well as to present meal-related information over different time periods. Change over time and from baseline will be assessed with ANOVA and t-tests, with correction for false discovery rates. Each meal-related parameter will be correlated with each other and with the 1-year weight loss, expressed as absolute total-body weight loss % excess BMI loss (% EBMIL). Explorative models will be generated using logistic regression to map meal-related information and optimal weight loss. All data will be analysed using RStudio.~Limitations~The present study has several limitations associated with the methods and the participants. First, the food data is self-recorded and prone to social desirability which may lead to inaccurate data. Indeed, the food preferences could be changed during the week of recording and some food items could may not be recorded. The database of food items and calories embedded in the app also may not be as accurate as expected. To reduce this limitation, the participants are asked to report any missing food items or incongruences reported by the app, and feedbacks are discussed with the app developer. Dietary self-monitoring is a key component in weight loss programs, and frequency of self-monitoring with a smartphone app is strongly correlated with weight loss. However, lean and obese controls of this study are not following any diet with the aim of weight loss and participants will record their food intake for a period that should not be long enough to induce changes in habits. Recent studies that attempted to validate the energy intake estimations by using PFR compared to the DLW method with obese participants found that this method was not accurate in estimating energy intake compared to DLW. However, in one case the TEE was measured in pregnant women who showed low compliance for reporting frequent intake of small meals. In the other one, the TEE was measured in minority preschool children whose intake was recorded by caregivers. Furthermore, both studies were cross-sectional studies. It is also reported that participants who use their own phones compared with participants who use borrowed phones capture more images and have higher accuracy , therefore such variable should also be considered in the data analysis. Technical problems with the phones may also be a source of underestimation. Training of the participants, constant communication and technical support must be provided in order to increase accuracy.~Relevance of the expected outcome for research or practice~This study would provide for the first time a direct and precise measurement of dietary intake in obese patients before and after RYGB. The direct PFR measurement with the mobile application SNAQ, validated by means of the DLW method, will allow to compare the energy intake of the three primary macronutrients per day (kcal/24h) and per meal (kcal/meal) between RYGB patients and controls. Furthermore, it could produce more fundamental information about human behaviour which will allow to translate for humans behavioural changes previously reported in rats. It is expected that patients will postoperatively and progressively adjust their relative caloric intake and food selection with a decrease of fat and sugars and an increase in complex carbohydrates, while non-operated controls will exhibit a stable, unaltered food selection and intake. The proposed research project is characterised by conceptual and methodological innovation. Food preferences and relative macronutrient intake within and between meals in patients after RYGB will be directly measured in a real life setting with PFR. This approach will overcome or reduce many of the limitations reported so far in the literature. If the expected outcome is confirmed, such a finding has the potential to fundamentally change clinical practice as regards to current post-bariatric nutritional counselling. Moreover, the results may also contribute to the development of less invasive interventions in the treatment of obesity and would justify a neurogenetic approach with animal models of obesity for mapping and studying neural circuits and linking specific brain activities to specific behaviours involved in obesity, as specified by the BRAIN initiative.

Direct measurements of changes in food selection in humans after RYGB have been limited by the unreliability of patients, which poses significant methodological and conceptual challenges to researchers and study design. Self-monitoring requires time and effort, and many find tracking of dietary intake tedious, which contributes to attrition. Direct measurements, however, represent an essential component in the attempt to understand how RYGB alters eating and food preferences, but laboratory settings preclude a real-life environment.~The aim of this study is to investigate changes in food preferences, total energy intake of the three primary macronutrients and meal patterns between obese women (BMI ≥ 35) before and after Roux-en-Y gastric bypass and lean (BMI ≤ 25) and obese (BMI ≥ 35) controls by means of photographic food recognition with a mobile application.

Compared to healthy weight peers, some reports have shown that they are less sensitive to, or perceptive of, sucrose solutions and sweet foods, whereas others have observed the opposite pattern of findings or no difference at all. Among those seeking weight loss treatment, one investigation found perception and preferences for sweet taste remained unchanged after weight loss, and another observed a decreased ability to distinguish sweet taste from other taste solutions. Given these discrepancies in the literature, the proposed study will explore whether a relationship exists between insulin and leptin resistance, sweet taste responsiveness, and adiposity.

This study will explore whether a relationship exists between insulin and leptin resistance, sweet taste responsiveness, and adiposity.

PURPOSE:~This study will be conducted to compare the effect of BFR with LLRT versus neuromuscular training on quadriceps muscle strength, knee joint function and proprioception accuracy.~BACKGROUND:~Patients with knee OA may have reduction of tolerance of the high-load programs which is recommended for eliciting strength gains (Messier et al., 2013). Thus, for reducing disease risk and enhancing physical function, there is a need for effectively strengthening the quadriceps muscle while limiting pain and adverse joint loading in people with knee OA (Segal et al., 2015). Blood flow restriction (BFR) with low-load resistance training (LLRT) is an alternative to traditional strength training that can be used in knee OA with minimal adverse joint loading that is normally found in traditional strengthening programs(Pope et al., 2013). It is attained through applying pressure externally with a pneumatic cuff or tourniquet. The applied pressure occludes venous outflow while maintaining arterial inflow with intent to promote blood pooling in the capillary beds of the limb muscles distal to the tourniquet (Slysz et al., 2016). Kubota et al., (2008), showed that BFR can be applied during periods of immobilization to decrease disuse muscle atrophy of limbs. Also it can be combined with exercise which enhances muscular development. Resistance exercise appears to provide great muscular gains when combined with BFR (Slysz et al., 2016).~HYPOTHESES:~There will not be a significant difference between traditional training, BFR with LLRT and neuromuscular training on improving quadriceps muscle strength using HHD in patients with unilateral knee OA.~There will not be a significant difference between traditional training, BFR with LLRT and neuromuscular training on improving knee joint function on WOMAC questionnaire in patients with unilateral knee OA.~There will not be a significant difference between traditional training, BFR with LLRT and neuromuscular training on improving knee joint proprioception in patients with unilateral knee OA.~RESEARCH QUESTION:~Does blood flow restriction with low load resistance training and neuromuscular training have a significant effect over traditional rehabilitation protocol (stretching and strengthening for hip and knee muscles) on quadriceps muscle strength, knee joint function and proprioception accuracy in patients with unilateral knee OA?

This study will be conducted to compare the effect of BFR with LLRT versus neuromuscular training on quadriceps muscle strength, knee joint function and proprioception accuracy.

Dietary intervention studies thus far have failed to be replicable or causal. The results, therefore, have failed to provide clinicians and the general public with consistent and useful information on which to base reliable food-related health decisions. This is particularly relevant regarding plastic-derived chemicals (PDCs), such as Bisphenol A, now that the federal CLARITY-BPA program has failed to achieve scientific consensus. Investigators propose a novel human dietary protocol that is both replicable and causal, based upon BPA's demonstrated inflammatory effects in humans. This first-of-a-kind dietary intervention study explores a potential causal relationship between human serum levels of BPA and High-Sensitivity C-Reactive Protein (hsCRP), a proven clinical indicator of inflammation. Investigators used the equivalent of a USDA-defined typical diet followed by a PDC-reduced diet to compare blood levels of hsCRP. This proof-of-concept investigation is the first to use an easily accessible, medically-accepted clinical laboratory test to directly measure human health effects of PDC reduction. Unexpected new complications discovered during the investigation indicate that these results may yet be inconclusive for direct causal relationship. However, the novel lessons and techniques developed as a result of those discoveries offer further specific and improved methods and best practices that can enable future dietary interventions to produce replicable, causal results.

Dietary intervention studies thus far have failed to be replicable or causal.This is particularly relevant regarding plastic-derived chemicals (PDCs),This first-of-a-kind dietary intervention study explores a potential causal relationship between human serum levels of BPA and High-Sensitivity C-Reactive Protein (hsCRP)

Background: Nurses play an essential role in transferring knowledge to patients. However, several factors cause nurses to adopt a negative attitude toward providing oncofertility care.~Objective: This study examined the effects of an oncofertility education program on decisional conflict in nurses caring for breast cancer patients and patients with breast cancer. Other predictors of decisional conflict were also examined.~Design: Randomized, controlled experimental research. Settings and Participants: Patients (61) with breast cancer and nurses (79) were recruited from a hospital in Taipei, Taiwan.~Methods: The nursing participants were randomly assigned to receive oncofertility education (experimental group) or usual education (control group). Data from female patients in the control and experimental groups were collected before and after the nurses' educational training, respectively. The oncofertility education consisted of one face-to-face educational session and reading one educational booklet based on the Naturalistic Decision-Making (NDM) Model. The decisional conflict was measured using the Chinese version of the decisional conflict scale.

his study examined the effects of an oncofertility education program on decisional conflict in nurses caring for breast cancer patients and patients with breast cancer. Other predictors of decisional conflict were also examined.

This is a single-arm study to evaluate the safety and efficacy of eltrombopag to treat chemotherapy-induced thrombocytopenia（CIT）. These subjects have been treated with recombinant human thrombopoietin（rhTPO） or interleukin 11（IL-11） before, the platelets can rise to normal or reach the effective standard, but after the re-application, the effective standard is not reached, or the effective standard is still not reached after the rhTPO 300U/kg/d treatment for 14 days. The investigator will assess the changes of the platelet counts after the treatment of eltrombopag from week 1 to week 24, and observe incidence of adverse events during the treatment of eltrombopag.The investigator will complete the 4 weeks safety visits（once a week），if the subjects end or withdraw from the clinical trial.~Patients with chemotherapy-induced thrombocytopenia who had the same inclusion and exclusion criteria in the same period or in the past will be compared with the efficacy and safety of supportive treatment in the same period or history, so as to preliminarily explore and evaluate the efficacy and safety of eltrombopag treatment.

To evaluate the efficacy and safety of eltrombopag to treat chemotherapy-induced thrombocytopenia in solid tumors

The investigators propose to test the implementation of a multifaceted, evidence-based, peri-operative surgical site infection (SSI) preventive program that leverages basic preventive measures optimized by pathogen cluster detection software (surveillance) to reduce ESKAPE (Enterococcus, S. aureus, Klebsiella, Acinetobacter, Pseudomonas, and Enterobacter spp.) transmission and SSIs. SSIs increase patient morbidity, prolong hospitalization, and increase the risk of death. ESKAPE pathogens are particularly problematic because they have increased capacity to acquire resistance and virulence traits. For example, S. aureus explains a significant proportion of SSIs. S. aureus transmission can be detected in 39% of surgical cases, has been directly linked to up to 50% of S. aureus SSIs by single nucleotide variant analysis, and is tightly associated with SSI development across a variety of surgical specialties. The isolation of ≥ 1 KAPE isolate from ≥ 1 intraoperative reservoir is associated with increased risk of infection development. The investigators have proven that improvements in basic perioperative preventive measures can generate substantial and sustained reductions in perioperative S. aureus transmission and SSIs, with the magnitude of the effect exceeding that of SSI preventive efforts focused on host optimization and inhibition of bacterial virulence strategies, the status quo. However, perioperative application of these basic preventive measures has been inconsistent, and some evidence suggests that S. aureus explains 20% of SSIs. Thus, there remains room for further advancement in perioperative infection control by addressing other ESKAPE organisms and by delineating an implementation approach that will yield effective, national dissemination of these proven measures. The investigators planned approach to address these pathogens mirrors our approach for perioperative S. aureus control, integrating evidence-based provider hand hygiene, intravascular catheter design/handling, environmental cleaning/organization, and patient decolonization improvement strategies with surveillance. The investigators surveillance approach maps the epidemiology of transmission of each pathogen, identifying for example, reservoirs of origin that become improvement targets for sustainability. While this approach is proven effective in preventing perioperative S. aureus transmission and SSIs, the relative effectiveness of the various components of the multi-faceted approach in reducing ESKAPE transmission and associated SSIs, as well as an effective national dissemination strategy, remain unknown. Therefore, the overall objectives for this study are to examine the relative effectiveness of each programmatic component in controlling ESKAPE spread and associated SSIs and to identify the best approach for national dissemination of this technology. The investigators will use a cluster-randomized design to evaluate the implementation and sustainability of each approach guided by RE-AIM framework. More broadly, these findings will be relevant to supporting hospital's implementation of a wide array of preventive interventions and has potential for vastly improving patient care and outcomes.

Surgical site infections (SSIs) are associated with increased patient morbidity, mortality, and healthcare costs. ESKAPE (Enterococcus, S. aureus, Klebsiella, Acinetobacter, Pseudomonas, and Enterobacter spp.) pathogens are particularly pathogenic because they have increased capacity to acquire resistance and virulence traits. The investigators have proven that a multifaceted program involving improved basic perioperative preventive measures can generate substantial reductions in S. aureus transmission and significant reductions in SSIs (88% reduction as compared to usual care). In this study, the investigators aim to examine the relative effectiveness of each component of this program in controlling ESKAPE transmission and reducing SSIs and to identify an optimal implementation strategy for national dissemination. Randomization occurs at the site level, and sites adopt preventative programs. This work will improve perioperative patient safety for the 51 million patients who undergo surgery each year.

To investigate the potential role of optical coherence tomography angiography in identifying the changes in retinal vessel density in patients that have been affected by COVID-19.~The optical coherence tomography angiography represents a noninvasive diagnostic technique that allows a detailed analysis of retinal vascular features.

This study evaluates the retinal vascular features using optical coherence tomography angiography in patients that have been affected by COVID-19.

For ATTRv-PN participants, Part 1 consists of an open-label, single-ascending dose study, which identifies the dose for evaluation in the cohort expansion of Part 2. Part 2 will follow as an open-label, dose expansion study to further characterize the activity of NTLA-2001, provide an initial assessment of the effect of NTLA-2001 on clinical measures of neuropathy and neurological function, and obtain additional safety data.~For ATTR-CM participants, Part 1 consists of an open-label, single-ascending dose study, which identifies the dose for evaluation in the cohort expansion of Part 2. Part 2 will follow as an open-label, dose expansion study to further characterize the activity of NTLA-2001, provide an initial assessment of the effect of NTLA-2001 on cardiac measures, and obtain additional safety data.~All participants who are dosed with NTLA-2001 will be offered to participate in a long-term safety monitoring follow-up study via a separate protocol.

This study will be conducted to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of NTLA-2001 in participants with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) and participants with hereditary transthyretin amyloidosis with cardiomyopathy (ATTRv-CM) or wild type cardiomyopathy (ATTRwt-CM)

Cholesterol-lowering drugs such as statins are currently used to lower cholesterol levels and prevent cardiovascular events. Statins have, however, received substantial scientific attention as cancer-inhibiting drugs. Previous findings were recently supported in a large-scaled study again demonstrating the beneficial effects of statins on breast cancer outcome this time nested within a large, international, randomized clinical trial of modern adjuvant cancer therapy. Given the compelling evidence supporting a protective effect of statins on breast cancer recurrence, calls for prospective clinical trials have been expressed. In this trial - the MASTER trial - we hypothesize that the addition of statin treatment to the current breast cancer treatment will improve the prognosis of women with early breast cancer. Thus, the primary objective of the MASTER trial is to determine the clinical efficacy of the statin - atorvastatin - as measured by invasive disease-free survival among patients with primary breast cancer.~The trial is nationwide throughout Denmark and a total of 3,360 women are to be included in the trial. Women eligible for the trial have been diagnosed with an estrogen receptor positive breast cancer and are candidates for systemic cancer therapy, either prior to or following breast surgery. Upon eligibility and signed informed consent, trial participants will be randomized in a 1:1 manner to either standard treatment and atorvastatin 80 mg/day or standard treatment and placebo. The randomization is blinded. The treatment with atorvastatin or placebo will continue for two years unless side effects are experienced and further treatment with atorvastatin or the placebo is deemed inadequate. The standard treatment will of course continue as planned. The trial participants will follow the standard clinical routines in terms of follow-up and in addition they are asked to fill in questionnaires, i.e. regarding potential side effects or new events or diagnoses, up to ten years following inclusion. Potential breast cancer recurrences are hereby identified and a follow-up of at least 61/2 years will be required for the trial the demonstrate the estimated clinical difference between the randomized groups of patients.

Given the compelling evidence supporting a protective effect of statins on breast cancer recurrence, calls for prospective clinical trials have been expressed. In this trial - the MASTER trial - we hypothesize that the addition of statin treatment to the current breast cancer treatment will improve the prognosis of women with early breast cancer. This trial is designed as follows: a randomized, multicenter, double-blind, placebo-controlled comparison of standard (neo)adjuvant therapy plus placebo versus standard (neo)adjuvant therapy plus atorvastatin in patients with early breast cancer.

This is a retrospective observational study that will examine the performance of the Shared Decision Making Process in a sample of patients who made a decision about cancer screening in the last 2 years. Patients from 4 hospitals who have received a patient decision aid for breast, colon, prostate, or lung cancer screening will be screened for eligibility. A random sample of eligible patients will be sent a one-time survey. The survey asks patients about their experiences talking with healthcare providers about the specific cancer screening decision. The survey includes the Shared Decision Making Process scale, knowledge, preferences, decisional conflict and decision regret. The study will obtain 400 completed surveys, or 100 for each cancer topic.~The sample consists of patients who received a decision aid for cancer screening within the last two years and meet specific qualifications.~All analyses will be conducted separately for each group, and results may be pooled. First, study staff examine the descriptives for the Shared Decision Making Process items. Study staff will also test several hypotheses to examine performance of the scores such as whether higher shared decision making process scores are associated with less decisional conflict and less regret.

The purpose of this retrospective observational study is to evaluate the performance of the Shared Decision Making Process scale in a sample of patients who have received a decision aid about the decision to screen or not screen for breast cancer, colon cancer, prostate cancer, or lung cancer.

Purpose: To investigate the clinical characteristics of papillary thyroid cancer (PTC) with Bethesda category III (AUS/FLUS) by fine needle aspiration (FNA) and to assisted the precision treatment.~Methods:A total of 1739 cases diagnosed with Bethesda category III (AUS/FLUS) by FNA from August 2015 to September 2020 were reviewed, and 523 patients received thyroidectomy or lobectomy. 290 patients were diagnosed with PTC and investigated retrospectively.~Groups: In order to investigate the clinopathologic characteristics, the patients, were grouped according to Cytology,Gender, Tumor size.as follows:AUS and FLUS&AUS/FLUS;male and female; tumor size≤1cm and>1cm.

Purpose: To investigate the clinical characteristics of papillary thyroid cancer (PTC) with Bethesda category III (AUS/FLUS) by fine needle aspiration (FNA) and to assisted the precision treatment.~Methods:A total of 290 patients who underwent thyroidectomies or thyroid lobectomies from August 2015 to September 2020, following a diagnosis of Bethesda category III (AUS/FLUS) from preoperative thyroid FNA were investigated.~Groups: In order to investigate the clinopathologic characteristics, the patients, were grouped according to Cytology,Gender, Tumor size.

Allergic rhinitis is a common inflammatory disorder of the nose that is increasing in prevalence worldwide. Symptoms of allergic rhinitis has a significant negative impact on an individual's quality of life. When the symptoms are not well managed with allergen avoidance and first line pharmacotherapies, patients often resort to using a combination of medications. Physicians may recommend combination therapies to patients with moderate-to-severe allergic rhinitis, however, there is a scarcity of research indicating efficacy of combination therapy use. The investigators of this study aim to evaluate the efficacy of combining oral antihistamine (rupatadine) with nasal steroid (fluticasone propionate) compared to a well-studied combination therapy of nasal steroid with nasal antihistamine spray (MP-AzeFlu) in people suffering from medium-to-severe allergic rhinitis. Oral rupatadine is a potent antihistamine and platelet activating factor (PAF) antagonist, which has not been studied in combination therapy in allergic rhinitis. Fluticasone propionate is a well established, first line nasal steroid.~Adults 19 years or older, seen in the Principal Investigator's office presenting with moderate-to-severe allergic rhinitis will be identified by the principal investigator and invited to participate in this prospective study. Patients will be recruited into the study in a consecutive manner. After providing consent, baseline characteristics will be collected. The investigator aims to recruit 51 patients in each study group respectively. Descriptive statistics will be used to analyze the baseline characteristic data.

Combination pharmacotherapy is often used in people who have failed mono-therapies in managing their bothersome allergic rhinitis symptoms . However, there is a paucity of research indicating the most effective combination therapies in managing allergic rhinitis. This study aims to evaluate the efficacy of oral antihistamine (rupatadine) combined with nasal steroid (fluticasone propionate) compared to a well-studied combination therapy of nasal steroid with nasal antihistamine spray (MP-AzeFlu).

Abbreviations/acronyms:~DUO-EF = prediction of ejection fraction (EF) using the Eko-DUO digital stethoscope algorithm HF = heart failure HFrEF = heart failure with reduced ejection fraction COVID-19 = coronavirus disease 2019 Eko DUO = digital stethoscope device cMRI = cardiac magnetic resonance imaging ECG = electrocardiogram~AIMS~To demonstrate DUO-EF can identify heart failure (HF) with reduced ejection fraction (HFrEF) post-COVID-19 where diagnosis would otherwise be missed/delayed To demonstrate DUO-EF can reliably and accurately diagnose new HFrEF in the primary care setting To further validate DUO-EF diagnostic performance at-scale against gold-standard investigations (echocardiography and cardia MRI) To measure if DUO-EF suggestive of HFrEF but with normal gold standard investigations predicts future risk of developing HFrEF~Methods To demonstrate DUO-EF can identify heart failure (HF) with reduced ejection fraction (HFrEF) post-COVID-19 where diagnosis would otherwise be missed/delayed To demonstrate DUO-EF can reliably and accurately diagnose new HFrEF in the primary care setting To further validate DUO-EF diagnostic performance at-scale against gold-standard investigations (echocardiography and cardiac magnetic resonance imaging - cMRI) To measure if DUO-EF suggestive of HFrEF but with normal gold standard investigations predicts future risk of developing HFrEF~DUO-EF prediction of ejection fraction in patients attending COVID-19 follow up clinic and comparison with:~subsequent DUO-EF at time of gold-standard investigation for HF ejection fraction as calculated by gold-standard investigation~DUO-EF prediction of ejection fraction in patients where their GP suspects new heart failure and comparison with:~subsequent DUO-EF at time of gold-standard investigation ejection fraction as calculated by gold-standard investigation DUO-EF prediction of ejection fraction in unselected patients attending for echocardiography or cardiac MRI, comparing DUO-EF predicted with gold-standard calculated ejection fraction Telephone call follow-up at 24 months for all patients with DUO-EF suggestive of HFrEF but normal gold standard investigations~OUTCOME MEASURES Area under curve (AUC) of DUO-EF calibrated for detection of EF below 40%; classification accuracy Positive predictive value of DUO-EF in COVID-19 clinic and GP context based on subsequent gold-standard estimation of EF; negative predictive value of DUO-EF in COVID-19 follow up cohort; positive predictive value of DUO-EF at 24 months in those with negative gold standard investigations Qualitative measurement of patient and clinical end user acceptability of Eko DUO~POPULATION Group 1: Patients seen in the COVID-19 follow-up clinic (n = 400) Group 2: Patients seen in primary care with symptoms newly suggestive of heart failure (n = 400) Group 3: All-comers to echocardiography departments across Imperial College Healthcare NHS Trust (n = 1,500) Group 4: patients undergoing cardiac MRI investigation (n = 100)

Abbreviations/acronyms:~DUO-EF = prediction of ejection fraction (EF) using the Eko-DUO digital stethoscope algorithm HF = heart failure HFrEF = heart failure with reduced ejection fraction COVID-19 = coronavirus disease 2019 Eko DUO = digital stethoscope device cMRI = cardiac magnetic resonance imaging ECG = electrocardiogram~Prospective observational study of left ventricular ejection fraction predicted by application of artificial intelligence to single-lead ECG acquired by a digital stethoscope; in the post-covid-19 follow up clinic, in patients presenting with heart failure symptoms in primary care, and in patients attending for echocardiography and cardiac MRI.

This clinical study is an open-label, multicenter, interventional, Phase 4 study to evaluate changes in genomic alterations for 73 PC driver genes during apalutamide treatment in patients with mCSPC. A total of 100 participants to be treated by apalutamide will be registered in this study. All participants will undergo blood collection for ctDNA, single-nucleotide polymorphisms (SNPs), and human-leukocyte antigen (HLA) typing at pre- and posttreatment of apalutamide.

To evaluate changes in genomic alterations for 73 PC driver genes during apalutamide treatment

The influence of sleep duration and sleep schedules (social jetlag) on glycemic control in type 1 diabetes has been shown in several previous studies, including by the investigators of this study.~Following these publications, patients have expressed the opinion via social networks that type 1 diabetes disease is itself a factor that alters the quality of sleep. Indeed, it appears that the cross-sectional studies published to date have focused on the association between the subjects' sleep habits and the balance of their diabetes, without having questioned the role of the pathology on sleep quality.~The main objective of this study is the objective evaluation of disease related sleep fragmentation in subjects with type 1 diabetes.

The main objective of this study is the objective evaluation of disease related sleep fragmentation in subjects with type 1 diabetes.

Most symptomatic large-to-massiverotator cuff tears (RCTs) should be operated, but the prognosis and postoperative risk of re-tear depended on the quality of rotator cuff muscles. Preoperative evaluations were usually done by magnetic resonance imaging (MRI). MRI was used in recent studies to predict the surgical outcome of large-to-massive RCTs and postoperative re-tear, but the clinical availability was not as good as ultrasound. The investigators hypothesize that ultrasound elastography can predict the prognosis of large-to-massive RCTs and risk of re-tear.

To predict the prognosis of large-to-massive RCTs and risk of re-tear by ultrasound elastography.

The aim of this study is to evaluate the clinical outcome after intraocular injections of Ranibizumab or combination of Ranibizumab and Dexamethasone under pro re nata treatment regimen for the patients with Diabetic Macular Edema patients. Mean change of logarithm of the minimal angle of resolution (logMAR) visual acuity (VA), central foveal thickness (CFT), contrast sensitivity (CS) as well as predictive factors including best-corrected visual acuity (BCVA), vision related questionnaires and various other ocular parameters will be assessed.

The aim of this study is to evaluate the visual outcome and prognostic factors after intraocular injections of Ranibizumab or combination of Ranibizumab And Dexamethasone under pro re nata treatment regimen for Diabetic Macular Edema patients.

The aim of this study is to evaluate the clinical outcome after intraocular injections of Bevacizumab or combination of Bevacizumab and Dexamethasone under pro re nata treatment regimen for the patients with Branch Retinal Vein Occlusion (BRVO) patients. Mean change of logarithm of the minimal angle of resolution (logMAR) visual acuity (VA), central foveal thickness (CFT), contrast sensitivity (CS) as well as predictive factors including best-corrected visual acuity (BCVA), vision related questionnaires and various other ocular parameters will be assessed.

The aim of this study is to evaluate the visual outcome and prognostic factors after intraocular injections of Bevacizumab or combination of Bevacizumab And Dexamethasone under pro re nata treatment regimen for Branch Retinal Vein Occlusion (BRVO) patients.

Retinal Venous Occlusive disease is the second only to diabetic retinopathy as a major cause of blindness associated with retinal vascular disease. Macular edema is a major cause of vision loss in patients presenting with central and hemi vein occlusions. Until recently the standard of care for macular edema secondary to central retinal vein occlusion was observation. Recent investigations of steroids for this condition has shown greater visual benefit but is associated with risks such as cataract formation and increased intraocular pressure. In the past laser photocoagulation has been used, but was found to offer no visual benefits over the natural history in the treatment of macular edema associated with CRVO.~Bevacizumab, an anti-VEGF agent, is a potent inhibitor of vascular permeability, with the potential to reduce retinal vascular leakage and diminish macular edema. In addition, as an anti-VEGF agent, it may also inhibit neovascularization of the iris, a frequent complication of ischemic central retinal vein occlusion. Bevacizumab use as an intravitreal agent does carry the risk of intraocular infection but probably carries very low risk of glaucoma or cataract formation, making it a potentially safer pharmacologic treatment for CRVO associated macular edema as compared to steroids.~Ozurdex (dexamethasone) Intravitreal Implant is a steroid injected into the eye to treat swelling that may occur when there is a blockage of certain blood vessels in your eyes. Ozurdex is also used to treat non-infectious uveitis affecting the posterior (rear) segment of the eye.

The purpose of this study is to determine whether Bevacizumab (Avastin) in combination with Dexamethasone (Ozurdex) will be effective in reducing if not eliminating the macular edema associated with the disease, central retinal vein occlusion (CRVO) in comparison to Bevacizumab (Avastin) alone.

This is a Phase 1b placebo-controlled, double-blind, randomized, single-dose safety study of intratympanic FX-322 dosed in subjects with age-related sensorineural hearing loss.~Approximately 30 subjects are planned to be enrolled in this study. The subjects will be randomized to receive one dose FX-322 (24) or placebo (6) and will return for safety, otologic, and audiologic assessments at Days 30 and 90 after the study injection.

This is a Phase 1b, prospective, randomized, double-blind, placebo-controlled, single-dose, multicenter, safety study of FX-322, administered by intratympanic injection, in adults with age-related sensorineural hearing loss.

This study evaluated the effectiveness and safety of sintilimab combined with cCRT in patients with locally advanced ESCC. The primary endpoint is PFS. Secondary points contains：ORR、OS、Qol.

This study evaluated the effectiveness and safety of sintilimab combined with cCRT in patients with locally advanced ESCC.

According to the 2012 Berlin diagnostic criteria, there are currently more than 3 million ARDS patients worldwide, accounting for about 10% of patients in the intensive care unit (ICU). In recent years, the incidence of ARDS has increased significantly, which has significantly increased the social and economic burden. The impact of ARDS can even be compared with tumors, AIDS or myocardial infarction. There are the basic clinical treatments, such as using various ventilation methods to improve hypoxia and choosing alternative therapies to improve renal insufficiency. Therefore, there is still a lack of specific treatment measures.~Exosomes are naturally occurring nanosized vesicles and comprised of natural lipid bilayers with the abundance of adhesive proteins that readily interact with cellular membranes. Studies have confirmed that MSC-Exos can improve most of the pathological changes caused by lung infection, reduce pulmonary edema, reduce protein exudation, reduce alveolar inflammation, and clear bacterial infections. Thus, it brings new hope for the treatment of ARDS.~The purpose of this study is to evaluate allogeneic human mesenchymal stem cell exosomes (hMSC-Exos) in the treatment of acute respiratory distress syndrome (ARDS)

To evaluate allogeneic human mesenchymal stem cell exosomes (hMSC-Exos) in the treatment of acute respiratory distress syndrome (ARDS)

This is a single-center, randomized, controlled trial (RCT), comparing bedside US-guided trocar technique versus the US-guided Seldinger technique for percutaneous cholecystostomy (PC). The study will randomize a total of 100 consecutive patients (50 in each group) undergoing PC at one large tertiary university hospital. The primary endpoints will be technical success and procedure-related complication rates. Secondary endpoints will be procedural duration, pain assessment, and clinical success after up to 3 months of follow-up.

A single-center randomized comparison of bedside ultrasound (US)-guided trocar technique versus the US-guided Seldinger technique for percutaneous cholecystostomy

The coronavirus disease of 2019 (COVID-19) is an international public health challenge with far-reaching social, economic and health impacts. Older adults and those with chronic underlying health conditions are the most susceptible to COVID-19 and its complications. Of the 15,381 reported cases of COVID-19 in Ontario to date, approximately 22.2% (n=3,420) are aged 60-79 and 22.4% (n=3,443) are 80 and over. Although there has been a rapid and coordinated response to studying the effects of COVID-19 in the acute stages, little is known about recovery over the longer-term. Anecdotally, the investigators are seeing severe declines in function, persistent symptoms, and new and worsening chronic conditions among older survivors of COVID-19. It is known that older adults who survive acute respiratory distress syndrome and associated diseases are at risk of developing persistent mobility limitations due to extensive bed rest and/or long stays in the intensive care unit (ICU) during hospitalization. Recent studies have shown that many older patients spend only 4% of their hospital stay out of bed, and each day in bed is associated with a 1-5% loss in muscle strength. For older patients and those with underlying frailty recovering from COVID-19, this could rapidly lead to significant physical deconditioning and rapid declines in mobility; with further losses in physiological reserve and resilience. Understanding the trajectory of functional recovery of older hospitalised patients with COVID-19 in the short- and long-term is critical to improving patient outcomes and informing health and rehabilitative interventions for survivors.~This study is an extension of the Coronavirus (COVID-19) Registry (COREG) platform (PI Andrew Costa)- a unique Kitchener-Waterloo-Hamilton registry of suspected and confirmed COVID-19 hospital admissions based on (and in collaboration with) the WHO International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). The addition of a prospective cohort study extension to COREG will allow the investigators to follow-older hospitalised COVID-19 patients over the longer-term in order to gain an understanding of the trajectory of functional recovery of the disease. Combining the primary data collection with COREG will also allow the investigators to identify determinants of long-term outcomes for at-risk older adults. These data are necessary to guide the clinical care and optimal management of older patients who survive serious COVID-19 illness.

Older adults and those with chronic underlying health conditions are the most susceptible to COVID-19 and its complications. Although there has been a rapid response to studying the effects of COVID-19 in the acute stages, little is known about recovery over the longer-term. Older adults who survive the diseases are at risk of developing persistent mobility limitations due to extensive bed rest during hospitalization. For older patients and those with underlying frailty recovering from COVID-19, this could rapidly lead to significant physical deconditioning and rapid declines in mobility. Understanding the trajectory of functional recovery of older hospitalised patients with COVID-19 in the short- and long-term is critical to improving patient outcomes and informing health and rehabilitative interventions for survivors.

China is a country with a heavy burden of gastric cancer and esophageal cancer. In 2015, the incidence/mortality of gastric cancer and esophageal cancer in China were 680000/500000 and 220000/200000, respectively. Gastroscopy is the most important means to detect early cancer of gastrointestinal tract. However, due to various factors, the miss rate of clinical significant lesions by gastroscopy is innegligible. Our previous research results showed that the detection rate of early gastric cancer and early esophageal cancer in China was only about 15%. This study aims to include 2000 gastroscopic procedures and investigate the relationship between procedure time and lesion detection rate in tertiary endoscopic centers in China.~At the first stage, the researchers observe the actual procedure time of gastroscopies without affecting the natural behavior of endoscopists. Then, researchers collect the data (including focal lesion detection rate, procedure time, detection rate of early upper GI cancer, biopsy rate and adverse event rate) and analyze the minimal procedure time. At the second stage, a minimal time limit will be set for each procedure. Every stage last two months, and potential correlations between lesion detection rate and procedure time will be investigated through subsequent statistical analysis.

This multicenter, prospective, interventional study aims to include 2000 gastroscopic procedures and investigate the relationship between procedure time and lesion detection rate in tertiary endoscopic centers in China. At the first stage, the researchers observe the actual procedure time of gastroscopies without affecting the natural behavior of endoscopists. At the second stage, a minimal time limit will be set for each procedure based on the observational results of the first stage. The primary study outcome is focal lesion detection rate. Secondary outcomes include detection rate of early upper GI cancer, biopsy rate and adverse event rate.

Ammonia is a waste product of protein and amino acid catabolism and is also a potent neurotoxin. The onslaught of high blood ammonia levels on the brain can manifest as cytotoxic brain edema and vascular compromise leading to intellectual and developmental disabilities. In addition, clinical hyperammonemia recurs at varying intervals, which can increase the cumulative damage to the brain and the chance of irreversible coma and death during a hyperammonemia episode due to vascular compromise or brain herniation. The threshold of tolerance for elevated blood ammonia is very low and concentrations above 100 µM can cause brain dysfunction manifested as nausea, vomiting, lethargy, and abnormal behavior; higher concentrations can cause coma and even death. Failure to remove ammonia can be due to inherited defects of the urea cycle, some defects in amino acid catabolism, and degradation of fatty acids.~Aim 1 - To determine the chronology of biomarkers of brain injury - S100B, NSE, and UCHL1 - in response to a hyperammonemic (HA) brain insult in patients with an inherited hyperammonemic disorder. We hypothesized that elevations of S100B, NSE, and UCHL1 will parallel the rise in blood ammonia. These biomarkers will be measured concurrently to ammonia levels throughout hospitalizations for HA until normalization of patient's blood ammonia and mental status.~Aim 2 - To determine if S100B, NSE, and UCHL1 are altered in patients with two other inborn errors of metabolism in which the primary pathology is neurological injury, Maple Syrup Urine Disease (MSUD) and Glutaric Acidemia (GA1). We hypothesize that neuronal and astroglial injury in these disorders may also result in increased levels of S100B, NSE, and UCHL1.~Metabolic patients will be enrolled either during a hospitalization or in outpatient clinic, but outpatient enrollment is preferred. Metabolic patients typically have multiple laboratory tests performed at their outpatient visits. We will obtain the discarded blood samples from such laboratory tests in order to measure S100B, NSE, and UCHL1 levels at baseline (normal blood ammonia), which will provide data on biomarker levels following recovery from a hyperammonemic episode.~During hospitalization for metabolic decompensation or for hypoxic-ischemic encephalopathy, sequential measurements of S100B, NSE and UCHL1 levels will be obtained from discarded blood samples. We will obtain S100B, NSE, and UCHL1 levels from collected discarded blood samples at all subjects' next outpatient visit following their hospitalization, to determine if levels return to baseline.

Ammonia is a waste product of protein and amino acid catabolism and is also a potent neurotoxin. High blood ammonia levels on the brain can manifest as cytotoxic brain edema and vascular compromise leading to intellectual and developmental disabilities. The following aims are proposed:~Aim 1 of this study will be to determine the chronology of biomarkers of brain injury in response to a hyperammonemic (HA) brain insult in patients with an inherited hyperammonemic disorder.~Aim 2 will be to determine if S100B, NSE, and UCHL1 are altered in patients with two other inborn errors of metabolism, Maple Syrup Urine Disease (MSUD) and Glutaric Acidemia (GA1).

Study ANK-700-01 is a Phase 1, FIH study designed to evaluate the safety and tolerability of ANK-700 in patients with relapsing remitting multiple sclerosis (rrms).~An overview of the two parts and proposed dose groups is given below:~Part A (SAD): Patients will receive a single dose of ANK-700. Part B (MAD): Patients will receive three doses of either ANK-700 or placebo.

A safety study of ANK-700 in patients with relapsing remitting multiple sclerosis. The study has two parts:~Part A - first in human study in which patients receive a single dose of ANK-700 Part B - patients will receive three doses of either ANK-700 or placebo

This will be a single-site, open-label study in symptomatic patients with IgG4-related disease affecting the submandibular and/or lacrimal glands. All patients will receive zanubrutinib orally at a dose of 80mg BID for 24 weeks.~The primary objective of this study is to demonstrate that zanubrutinib treatment reduces reduces the volume of the submandibular and/or lacrimal glands on PET/MRI at week 24 compared to baseline.

The aim of this clinical trial is to evaluate the safety and efficacy of zanubrutinib in treating patients with IgG4-related disease

Type 2 diabetes (T2D) as a common antecedent of pathological neurodegeneration and dementia, including Alzheimer's Disease (AD); yet the mechanistic link between metabolic and neurodegenerative disorders remains unresolved. Here, the investigators will study a well-defined human population with increased prevalence and early onset of both T2D and AD, individuals of Mexican descent living in South Texas. The study will lay critical groundwork toward addressing the investigators' overarching hypothesis that dysbiosis of the gut microbiome in type 2 diabetic individuals of Mexican descent living in South Texas is causally related to the increased prevalence of comorbid, early onset AD in this population. In this study, the investigators will perform state-of-the-art metagenomic 16S ribosomal RNA (rNRA) gene sequencing and bioinformatic analysis on fecal samples collected from type 2 diabetic and non-diabetic control individuals of Mexican descent to test the working hypothesis that the community structure of the gut microbiome of individuals of Mexican descent with T2D is significantly altered compared to that of nondiabetics within the same population. To the investigators' knowledge, this multidisciplinary pilot study will be the first to investigate the gut microbial community structure of type 2 diabetic versus that of nondiabetic individuals of Mexican descent. Furthermore, it has the potential to provide mechanistic insight into how T2D predisposes individuals to the neuropathology and cognitive impairment characteristic of AD and to identify a novel class of interventions that target the host gut microbiome for the prevention of early onset AD in a predisposed population, as well as the population at large.~Human subjects will be recruited through the University of Texas Medical Branch at Galveston (UTMB) Endocrinology and pre-screened to confirm that the potential participants meet established inclusion and exclusion criteria as either T2D or nondiabetic controls, as defined in the UTMB human subjects protocol associated with this project. Pre-screened participants that meet the defined criteria will be invited to attend an appointment with a study coordinator held at the UTMB Clinical Research Center. Consented and enrolled study participants will be asked to complete medical history, dietary preference, and gastrointestinal function questionnaires and instructed as to how to use the provided OMNIgene-GUT RNA (OMR)-200 fecal sample collection kit (DNA GenoTek). Participants will submit the collected fecal sample via shipment of a pre-paid and labeled shipping envelope. Samples will be deidentified and stored at -80oC in the Buffington Lab prior to shipment to the Baylor College of Medicine Center for Metagenomic and Microbiome Research (CMMR) for metagenomic 16S rRNA gene sequencing. Briefly, bacterial genomic DNA will be extracted using the MagAttract PowerSoil Kit (Qiagen) and the 16S ribosomal DNA (rDNA) V4 region will be amplified by polymerase chain reaction (PCR) and sequenced on the MiSeq platform (Illumina). 16S rRNA gene read pairs will be demultiplexed based on unique molecular barcodes added to primers used for amplification and reads will be merged using USEARCH. 16S rRNA gene sequences will be clustered into Operational Taxonomic Units (OTUs) using the UPARSE algorithm and mapped to an optimized version of the SILVA database to determine taxonomies. The investigators will then use a custom script developed by the CMMR to construct a rarefied OTU table for downstream analyses of alpha-diversity, beta-diversity, and phylogenetic trends to identify any changes in community structure between type 2 diabetic and non-diabetic individuals of Mexican descent enrolled in the study.

Type 2 diabetes (T2D) predisposes individuals to neurodegeneration and dementia, including Alzheimer's Disease (AD); yet the link between metabolic and neurodegenerative disorders remains unknown. Here, the investigators will study a well-defined human population with increased prevalence and early onset of both T2D and AD, individuals of Mexican descent living in South Texas. The study will begin to explore the possibility that disruption of the structure of the bacterial community residing in the gut in type 2 diabetic individuals of Mexican descent living in South Texas is directly related to the increased prevalence of early onset AD in this population. In this study, the investigators will perform gene sequencing on DNA isolated from fecal samples to identify and compare the populations of bacteria living in individuals with T2D versus non-diabetic controls. The investigators will analyze the findings to determine if the community structure of the gut microbiome of individuals of Mexican descent with T2D is significantly altered compared to that of non-diabetics within the same population. The investigators' findings could lead to the identification of early indicators of dementia onset as well as novel therapies for treating metabolic and neurodegenerative diseases.

Optimal time for follow up after variceal band ligation in cirrhotic patients remains to be determined. So, we designed this trial to answer this question.

Optimal time for follow up after variceal band ligation in cirrhotic patients remains to be determined

Background: The pregnancy rate after cancer treatment for female survivors is lower than that of the general population. Future infertility is a significant concern for patients with breast cancer and is associated with a poor quality of life. Reproductive- age patients with breast cancer have safe options when choosing the type of fertility preservation method to be applied. Better information and support resources aimed at women to support their decision making are needed.~Objective: The objective of this study was to develop a web-based, shared decision-making (SDM) tool for helping patients with breast cancer make decisions on fertility preservation.~Methods: We used the action research cycle of observing, reflecting, planning, and acting to develop a web-based SDM tool. The following four phrases were applied: (1) Observe and reflect: Collect and analyze the decision-making experiences of patients and health care providers; (2) Reflect and plan: Apply the initial results to create a paper design and modify the content; (3) Plan and act: Brainstorm about the web pages, and modify the content; (4) Act and observe: Evaluate the effectiveness, and refine the website SDM. Interviews, group meetings, and constant dialogue were conducted between the various participants at each step. The effectiveness was evaluated using the Preparation for Decision-Making (prepDM) scale.

The objective of this study was to develop a web-based, shared decision-making (SDM) tool for helping patients with breast cancer make decisions on fertility preservation.

Following glaucoma surgery, patients often experience decreased visual acuity (VA) which can partly be explained by induced changes to the optical properties of the cornea. Corneal astigmatism can be assessed using corneal topography, a non-invasive tool which provides an accurate estimate of corneal curvature in all meridians. Obtained keratometric measures (termed K values) can allow clinicians to quantify the amount of astigmatism before and after surgical intervention.~Multiple studies have been previously published to evaluate induced postoperative astigmatism after trabeculectomy. However, only two studies have characterized the impact of GDDs on keratometric values. To the best of our knowledge, no study has yet attempted to quantify the amount of astigmatism induced by the XEN Gel Stent.~Assessing the impact of the XEN implant on corneal astigmatism is important to better characterize the expected course of postoperative visual rehabilitation, the impact of novel glaucoma devices on corneal properties and the predictability of refractive outcomes after XEN implantation. Compared to traditional filtering surgery, the XEN Gel Stent is inserted without opening the conjunctiva and is implanted further from the corneal limbus (5 mm). These factors may allow for a reduced amount of surgically induced corneal astigmatism.~We hypothesize that the XEN Gel Stent implantation induces less corneal astigmatism compared to traditional filtering surgery, such as the trabeculectomy and GDDs (BGI or AGV).~The main goal of this prospective interventional comparative study is to assess the severity of postoperative corneal astigmatism induced by implantation of the XEN Gel Stent compared to that induced by traditional filtering surgery (trabeculectomy and GDDs).~Secondary objectives are evaluation of visual acuity recovery as well as IOP reduction and other parameters between groups.~Glaucoma surgery (XEN Gel Stent, trabeculectomy or GDD implantation) will be performed by the ophthalmologists in charge of the study according to standard procedures. For each patient, the most appropriate type of glaucoma surgery will be recommended by the ophthalmologist regardless of patients' participation in the study, as dictated by the specific nature of their glaucoma and following current standards of care.

The main goal of this study is to assess the severity of postoperative corneal astigmatism induced by implantation of the XEN Gel Stent compared to that induced by traditional filtering surgery (trabeculectomy and GDDs). Corneal astigmatism can be assessed using corneal topography, a non-invasive tool which provides an accurate estimate of corneal curvature in all meridians. To the best of our knowledge, no study has yet attempted to quantify the amount of astigmatism induced by the XEN Gel Stent.

This is a multicenter, randomized, double-blind, placebo-controlled, parallel-cohort, dose-ranging study of participants with mild to moderate plaque psoriasis. This Phase 2 study has been designed to investigate the clinical safety and efficacy of EDP1815 and to identify an optimal dose in subjects with mild to moderate psoriasis.

This Phase 2 study has been designed to investigate the clinical safety and efficacy of EDP1815 and to identify an optimal dose in subjects with mild to moderate psoriasis.

The investigators hypothesize that co-administration of a 5-HT3 receptor antagonist ondansetron (single 16mg dose) with p-glycoprotein inhibitor tariquidar (single 4mg/kg dose) vs placebo in a cross-over prospective randomized study, will:~Be tolerable in patients with neuropathic pain.~Increase the cerebrospinal fluid (CSF) to plasma ratio of ondansetron after intravenous administration, compare to ondansetron alone~Result in a greater reduction in pain intensity than with ondansetron alone.

Prospective, randomized, double-blind, placebo controlled, cross-over proof of concept study.~To determine the pharmacokinetics and tolerability of co-administration of 5-HT3R antagonist ondansetron with a P-glycoprotein inhibitor tariquidar, in patients with neuropathic pain.

Nurses are frontline practitioners in the fight against COVID-19. Empowering nurses through training for infection prevention for COVID-19 is an essential step to facilitate nurse leadership and safety in the hospital. There is immense reliance on nurses with regard to patient safety, yet very little effort is made to invest in interventions for their leadership roles in developing countries, including Pakistan. In this study the aim is to deliver an intervention for COVID-19 preventive protocols to nurses and assess the impact of the intervention through a pre and post-test survey. A total of 200 nurses will be sampled. A 100 nurses each will be part of the control and experiment group each.~The data will be analyzed using SPSS. Pre and post test results will be presented using descriptive data and bivariate regression will be used to present higher odds of confidence in preventive and awareness literacy for COVID-19 in nurses after intervention delivery. Through this research the aim is to improve nurse leadership in maintaining minimum service delivery standards for hospital infection control with respect to COVID-19; but also other infectious disease burden management.

The aim is to deliver an intervention to promote nurse leadership and decision-making in the hospital setting, by providing them with training for maintaining minimum service delivery standards for hospital infection control with respect to COVID-19; but also other infectious disease burden management.

Dry Eye Disease is a multifactorial disease that affects approximately 15-30 million people in the United States alone. it creates an enormous societal and economic burden, decreases productivity in our workplace, and significantly affects the quality of lives of the people affected by this disease. Appoximately 86% of Dry Eye Disease is caused by Blepharitis, a chronic inflammation of the eyelid margins. If left untreated, Blepharitis results in the obstruction and eventual loss of the glands responsible for a critical component of tear film production.~The standard of care in the treatment of Blepharitis is the use of self administered at home commercially available products such as eyelid foams, gels, and pre moistened pads. These products contain non abrasive cleansers designed to remove the buildup of biofilm and excess microorganisms on the lid margin. Although these products are helpful, they do have some limitations. Many patients still require more expensive in office procedures such as lid debridement with electro-mechanical exfoliation devices or other even more expensive procedures.~The scope of this project is to evaluate the effectiveness of a new self administered disposable ocular brush used in conjunction with the most commonly prescribed commercially available eyelid cleanser. The investigators are looking to see if combining the microexfoliation provided by the brush with the eyelid cleanser is more effective at removing the eyelid debris (scurfs, collarettes, and demodex) than the cleanser alone.~Hypothesis: The Summit Ocular Brush used in conjunction with Ocusoft Original lid cleanser is more effective than the cleanser alone at removing the debris (scurfs, collarettes, and demodex) from the eyelids in the treatment and management of Blepharitis.~The investigators want to determine if the addition of the ocular brush with the eyelid cleanser has synergistic effects on reducing the signs and symptoms of Blepharitis and Dry Eye Disease. They also hope to learn that with this additional step, further and more expensive procedures could be avoided thereby decreasing the overall economic burden on the patient and society as a whole.~Recruitment of participants: Dr. Kevin Danahey, Dr. Richard Mangan, and Dr. Paul Karpecki are the three clinical investigators for this multi-site study. They are all directors of Dry Eye Clinics and regularly see patients throughout the course of the day. Potential participants will be identified during routine office visits. Participants will be identified by subjective symptoms and objective signs of Blepharitis. The SPEED (Standardized Patient Evaluation of Eye Dryness) Questionnaire will be utilized to identify symptoms and Slit Lamp Biomicroscopy will be used to identify objective clinical signs of Blepharitis. Once patients are identified as potential candidates, they will be informed by the investigator that they are a candidate for a study and asked if they would be interested in participating. A brief explanation of the study will be given and the patient will be informed that regardless of which group they are assigned to, they would still be receiving the current standard of care. The candidates would then be asked to return so that the Investigators may provide informed consent, thorough written and verbal instructions, HIPPA forms, SPEED questionnaires, and treatment products. The patients would also have digital photos and video performed with Slit Lamp Biomicroscopy at that time. These images would only involve the lids and lashes of the subjects allowing the investigators to protect the identity, gender, and age of the subject.~Study: This multi-site study will involve 60 subjects. Each site will have 20 participants. Each site will divide participants into two groups of 10. The control group will receive the standard of care. The standard of care would be Ocusoft Lid Scrub Original Foaming Eyelid Cleanser to be used once per day. The treatment group would receive the same treatment as the control group with the addition of the experimental disposable ocular brush. The foam will be applied to the brush and the subjects will gently provide a scrubbing action to the eyelids while keeping the eyelids closed. They will also be instructed to perform treatment once per day and to dispose of the brush after two weeks and replace it with a new brush.~Each participant will be asked to return to their respective site for two follow up visits. The first visit will take place at two weeks commencing treatment and the final visit will take place two weeks later for a total treatment duration of one month. During each visit, the subjects will fill out the SPEED questionnaire and digital images and videos will be taken. The length of each visit should take no longer than 15 minutes. At the conclusion of the study, subjects in the treatment group will be asked to discontinue the experimental brush. They would be asked to continue with the current standard of care.~All SPEED scores and digital images would then be de-identified to avoid any bias by the principal investigator and his research staff. These scores and images would be uploaded and sent electronically via encrypted password protected file to Giles Duffield, PhD. for interpretation and statistical analysis.~Anterior blepharitis is an ophthalmologic condition characterized by an inflammation of the eyelid margins. It can be acute or chronic with chronic being the more common form. Blepharitis is a clinical diagnosis based on irritation of the lid margins with flaking and crusting of the lashes.~The main treatment for blepharitis is good eyelid hygiene and elimination of triggers that exacerbate symptoms (Pflugfelder SC, Karpecki PM, Perez VL. Treatment of blepharitis: recent clinical trials. Ocul Surf. 2014 Oct;12(4):273-84).~Blepharitis is not specific to any group of people. It affects people of all ages, ethnicities, and gender. It is more common in individuals older than the age of 50. The total number of cases in the US at any one time is not known. In a 2009 US survey, 37% of patients seen by an ophthalmologist and 47% of patients seen by an optometrist had signs of blepharitis.~The exact pathophysiology of blepharitis is not known. The cause is most likely multifactorial. Causative factors include a combination of chronic low-grade bacterial infections of the ocular surface, inflammatory skin conditions such as atopy and seborrhea, and parasitic infestations with Demodex mites.~There are a number of products on the market that aid in reducing the inflammatory and bacterial load to the lid margin and lashes. However, mechanical debridement (or lid scrubs) is best at removing debris and the bacterial biofilm that forms in chronic cases. As one ages, near vision and dexterity worsens. Timely and appropriate lid hygiene then suffers that may result in lid and ocular infection, as well as vision loss.~The Summit Ocular Brush proposed here should improve the effectiveness of personal home lid hygiene, even in an aging population. This is what the Investigators wish to study.~The experimental design includes one experimental group and one control group. Subjects will be divided up such that each clinic collects 10 subjects from each group. This will provide us with 30 experimental and 30 control subjects and spread evenly between the three separate clinical locations. Data analysis will be of still images taken from video and photographic images of the eye lid margins.~Data will be in the form of counts of eyelid debris, specifically 1) scurfs, 2) collarettes, and 3) demodex. Analysis will be performed by Dr. Duffield and his team at the University of Notre Dame and will be performed blind. Each subject data set will only be identifiable by a code, which will not allow for prior knowledge of origins of treatment group. The n=30 sample size is deemed appropriate for the application of standard statistical methods on continuous data, specifically parametric t-test or non-parametric Mann-Whitney test. Analysis at the subgroup level (with 3+ groups), such as incorporation of gender or age fractionation, parametric ANOVA or nonparametric Kruskal-Wallis tests will be performed on the data, followed by post-hoc pair wise comparison tests. In all cases, alpha will be set at 0.05, i.e. p< 0.05 will be seemed significant. The relatively large sample size of 30 subjects in each main group affords us the opportunity to examine subgroup affects without concern that the Investigators have insufficient numbers of subjects.~Lid Scrubs are listed at every stage of the treatment algorithm for anterior blepharitis. As patients age, their ability to perform proper lid scrubs / hygiene declines. Without proper mechanical debridement of lid and lash flakes, scurfs, collarettes, or mites, this condition can remain chronic or recalcitrant. Chronic use of topical antibiotics promotes bacterial resistance and chronic use of steroids puts patients at risk for infection and elevated intra-ocular pressure. With sound and proper debridement technique using the Summit Ocular Brush, this should lesson the need for such prescription medication.~Patients will be followed by their doctor's normal standard of care protocol.~The experimental design includes one experimental group and one control group.~Subjects will be divided up such that each clinic collects 10 subjects from each group. This will provide us with 30 experimental and 30 control subjects and spread evenly between the three separate clinical locations. Data analysis will be of still images taken from video and photographic images of the eye lid margins. Data will be in the form of counts of eyelid debris, specifically 1) scurfs, 2) collarettes, and 3) demodex. Analysis will be performed by Dr. Duffield and his team at the University of Notre Dame and will be performed blind. Each subject data set will only be identifiable by a code, which will not allow for prior knowledge of origins of treatment group. The n=30 sample size is deemed appropriate for the application of standard statistical methods on continuous data, specifically parametric t-test or non-parametric Mann-Whitney test. Analysis at the subgroup level (with 3+ groups), such as incorporation of gender or age fractionation, parametric ANOVA or nonparametric Kruskal-Wallis tests will be performed on the data, followed by post-hoc pair wise comparison tests. In all cases, alpha will be set at 0.05, i.e. p< 0.05 will be seemed significant. The relatively large sample size of 30 subjects in each main group affords us the opportunity to examine subgroup affects without concern that the Investigators have insufficient numbers of subjects.~Patients will be followed by their doctor's normal standard of care protocol. Participants can be both male and female over the age of 18 with clinical signs and symptoms of Blepharitis (Staphylococcal and Demodex). Participants must exhibit visible collarettes, clear sleeves, and scurfs on the eyelid margins upon Slit Lamp Biomicroscopy.~Participants both male and female under the age of 18. Patients with any active hordeolum (stye), chalazion, periorbital cellulitis, or any evidence of allergic eyelid dermatitis. Participants will also be excluded if they have any active acute bacterial conjunctivitis or any active open periorbital wounds.

Dry Eye Disease (DED) is a multifactorial disease that affects ~15-30 million people in the USA alone. It creates an enormous societal and economic burden, decreases productivity in the workplace, and affects the quality of lives of the people affected by this disease. DED is primarily caused by blepharitis, a chronic inflammation of the eyelid margins. If left untreated, blepharitis results in the obstruction and loss of the glands responsible for tear film production. The standard of care is the use of self-administered at home commercially available products, e.g., eyelid foams, gels, and pads. Although these products are helpful, they have limitations. Patients often require expensive in office procedures, e.g., lid debridement with exfoliation devices or more expensive procedures. The scope of this project is to evaluate the effectiveness of a new self-administered disposable ocular brush used in conjunction with the most common eyelid cleanser. The investigators are looking to see if combining the microexfoliation provided by the brush with the eyelid cleanser is more effective at removing the eyelid debris than the cleanser alone.

Allergic rhinitis (AR) is an inflammatory state characterized by a disturbance of immunoregulatory mechanisms that leads to an amplified T helper Th-2 response. Micro-RNAs (miRNAs) are short single-stranded RNA molecules that post transcriptionally control gene expression and can mediate allergic process. The aim of this study was to explore miRNA-155 change in response to sublingual immunotherapy (SLIT), probiotics and combined treatment with SLIT and probiotics in AR children.

The investigators aimed to explore miRNA-155 change in response to sublingual immunotherapy (SLIT), probiotics and combined treatment with SLIT and probiotics in AR children.

Children generally undergo induction of anesthesia by inhalation of sevoflurane. This is particularly relevant for children with developmental delays as to avoid placement of an IV while awake. However, children with Down Syndrome experience bradycardia with induction of anesthesia using sevoflurane. It is unknown if this bradycardia is isolate or results in hypotension, thus requiring treatment. Isolate bradycardia without hypotension does not require treatment and should be avoided as many of these patients have underlying cardiac anomalies.

Children generally undergo induction of anesthesia by inhalation of sevoflurane. Children with Down Syndrome experience bradycardia with induction of anesthesia using sevoflurane. It is unknown if this bradycardia is isolate or results in hypotension, thus requiring treatment. Isolate bradycardia without hypotension does not require treatment and should be avoided as many of these patients have underlying cardiac anomalies.

We propose a pragmatic randomized controlled trial to test two interventions targeting clinical inertia in hypertension compared to control, followed by predictive modeling to identify factors that are associated with intervention responsiveness.~For Aim 1, we will use Electronic Health Record (EHR) data to identify physicians of patients whose hypertension treatment was not intensified despite their having persistently elevated blood pressure. We will then randomize primary care physicians to on of three arms: academic e-detailing, social norming, or no intervention (control).~For Aim 2, we will conduct interviews with select physicians from each arm. We will then identify patient and physician characteristics that are associated with inertia and with responsiveness to each intervention.

This is a three-arm pragmatic randomized controlled trial to test two interventions targeting clinical inertia in hypertension compared to control, followed by predictive modeling to identify factors that are associated with intervention responsiveness. Study investigators will use EHR data to identify providers of patients whose hypertension treatment was not intensified. Primary care physicians will then be randomized to one of three arms: pharmacist e-detailing, provider dashboards, or no intervention (control). After the intervention, the investigators will conduct virtual interviews with select providers from each arm. A predictive modeling approach will then be used to identify patient and provider characteristics that are associated with inertia and with responsiveness to each intervention.

Bladder cancer (BC) is a common cancer worldwide and one of the most expensive to manage. This disease accounts for 6-8% of all male malignancies and 2-3% in women. Non muscle invasive bladder cancer (NMIBC) represents about 70% to 80% of bladder cancer. Of these, 70 % present as T1, 20 % as Ta, and 10 % as carcinoma in situ (CIS).~Many NMIBCs are amenable to treatment with transurethral resection of bladder tumor (TURBT) alone. However, despite the therapeutic impact of TURBT, bladder cancer (BCa) recurrence rate can be as high as 75%.~The significant risk of residual tumor after initial TURBT of NMIBC lesion has been demonstrated in many studies. Persistent disease after resection of T1G3 tumors has been observed in nearly 33% to 53% of patients after TURB. Moreover, the tumor is often understaged by initial resection, so the likelihood that a T1 tumor has been understaged and muscle-invasive disease is detected by second resection ranges from 4% to 25%.~Treatment of a Ta, T1 high-grade tumor and a T2 tumor is completely different, so correct staging is therefore important. It has been demonstrated that a second TURBT in patients with T1G3 tumor can increase recurrence-free survival.~A second look TURBT is recommended in the following situations; 1- After incomplete initial TURBT. 2- If there was no muscle in the specimen after initial resection. 3- In all T1 tumors. 4- In all G3 tumors.~These findings lead to many studies which reported on the development of new methods to avoid residual tumor at initial resection as narrow band imaging versus white light imaging. However, such evolutions cannot omit the need for second resection.~Despite its valuable role in completion the diagnosis and proper risk categorization of NMIBC, Second look TURBT is still considered an accessory invasive procedure with more added surgical risks of anesthetic and surgical complication as bleeding and perforation. In addition, the cost issue of hospital stay and operating theatre is a major consideration. Recent studies are searching for a less invasive tool that can replace or at least refine the role of second look TURBT.~The Xpert BC Monitor is an mRNA-based urinary marker test for BC surveillance which measures the levels of five target mRNAs (ABL1, ANXA10, UPK1B, CRH and IGF2) from a voided urine sample by real-time RT-PCR. The Xpert BC Monitor automates and integrates sample processing, nucleic acid amplification, and the detection of target sequences.~The performance of Xpert BC monitor regarding its sensitivity and negative predictive value was shown to be considerably high reaching 84% and 93%, respectively. Moreover, this high sensitivity was maintained in low-grade (77%) and Ta tumors (82%). Xpert BC monitor is going to gain now a wide popularity among practitioners in surveillance of NMIBC patients due to its simplicity to do, reliability and reproducibility.~The investigators hypothesize that; Xpert BC monitor may be a useful tool in evaluation of patients, who are potentially candidates for repeat TURBT. It can refine the indications of repeat biopsy by exclusion of cases with negative test.

The Xpert BC Monitor is an mRNA-based urinary marker test for BC surveillance which measures the levels of five target mRNAs (ABL1, ANXA10, UPK1B, CRH and IGF2) from a voided urine sample by real-time RT-PCR. The Xpert BC Monitor automates and integrates sample processing, nucleic acid amplification, and the detection of target sequences.~The performance of Xpert BC monitor regarding its sensitivity and negative predictive value was shown to be considerably high reaching 84% and 93%, respectively. Moreover, this high sensitivity was maintained in low-grade (77%) and Ta tumors (82%). Xpert BC monitor is going to gain now a wide popularity among practitioners in surveillance of NMIBC patients due to its simplicity to do, reliability and reproducibility.~The investigators hypothesize that; Xpert BC monitor may be a useful tool in evaluation of patients, who are potentially candidates for repeat TURBT. It can refine the indications of repeat biopsy by exclusion of cases with negative test.

After the approval of the ethics committee for the study, in the Istanbul University Faculty of Medicine Orthopedics and Traumatology Department; There will be 3 or more posterior instrumentation operations, cobb angle of 40 degrees and above, 18-75 years old, ASA (American Society of Anesthesiologists) score 1-3, no chronic neuropathic pain and no psychiatric illness, no chronic narcotic analgesics and / or substance abuse a creatine value below 1.3 will be included.~Standard anesthesia monitoring will be performed for patients taken to the operation room. Routine anesthesia induction will be performed. In the prone position, anesthesia maintenance will be provided using the infusion of propofol and remifentanil.~Our clinic; PCA (patient-controlled analgesia) device with intravenous morphine is used routinely for postoperative analgesia.In this study ;two randomized groups will be created. It will give iv magnesium(in the intraoperative period at a dose of 40mg / kg, within 30 minutes after induction) to a blindly designated group. The other group will be given only isotonic. After in post-operative period, magnesium infusion will be continued for 12 hours (40mg / kg). Magnesium sulfate will be given in 100 cc isotonic. In the other group, only 100cc isotonic will be given without using magnesium. All patients will be awakened after the analgesic agents (0,1mg / kg morphine, 15mg / kg paracetamol, nsaid) are used in routine practice and will be followed up for intensive care.~The use of PCA device is available in both groups. vas score will be recorded postoperative 30. minutes and 2,6,12,18,24 hours. In routine administration, the patient should be given 2 mg of morphine if vas>4 and the maximum dose will be increased to 10 mg.

In this study ; Two randomized groups will be created. Iv magnesium will be given to one of the blindly designated groups. The other group will be given only isotonic. All patients will be awakened after the analgesic agents (0,1mg / kg morphine, 15mg / kg paracetamol, nsaid) are used in routine practice and will be followed up for intensive care.~The use of PCA (patient controlled analgesia) device is available in both groups.In post-operative period, magnesium infusion will be continued for 12 h. Only 100cc isotonic will be given without using magnesium to the other group. VAS (visual analog scale) score will be recorded at postoperative 30. minutes and 2,6,12,18,24 hours. In routine administration, the patient should be given 2 mg of morphine if vas>4 and the maximum dose will be increased to 10 mg.

Background The World Health Organization (WHO) defines overweight as a body mass index (BMI) of ≥25 kg/m2 and obesity as a BMI of ≥30 kg/m2. Overweight and obesity are rising dramatically worldwide. In fertile women, the prevalence of obesity is one third in the United States, 20% in the United Kingdom, and 12-13% in Denmark. The association between obesity in pregnancy and the risk of gestational complications increases with increasing BMI. Among other complications, obesity in pregnancy is associated with increased risk of caesarean delivery. Delivery by caesarean section further adds significant risks of wound infection or other infectious morbidity in obese women as compared to normal weight women. The longer the woman is pregnant, the longer the risk of pregnancy complications remains. In an otherwise low-risk pregnant woman at term, it is an on-going clinical dilemma, whether the benefits of elective induction of labor (eIOL) and termination of the pregnancy will outweigh the potential harms from the concomitant induction and delivery process. Regarding delivery complications, based on data from historical cohorts, eIOL has traditionally been associated with an increased risk of caesarean section and instrumental delivery. Therefore, expectant management has been the preferred clinical option. This interpretation has now been challenged by a randomized trial (ARRIVE) with >6000 low-risk pregnant women where eIOL at 39 weeks of gestation was associated with lower caesarean delivery rates. There are no randomized studies in obese women, but two larger observational studies did find lower odds of caesarean delivery in obese women with eIOL as compared to awaiting labor onset. Hence, a randomized trial that would compare caesarean delivery among obese women whose labor is induced with those expectantly managed is warranted. The proposed study will provide new and important knowledge into the area of induction of labor among overweight and obese women with potential great international impact for the future raising number of pregnant women in this subgroup.~With this trial, the investigators aim to compare the risk of caesarean section in obese (BMI ≥ 30 kg/m2), but otherwise low-risk women with eIOL as compared to expectant management.~Materials and methods~The study is a multicenter randomized controlled trial with an allocation ratio of 1:1 in the two following arms:~Intervention arm/elective induction of labor in pregnancy at 39 gestational week and 0 to 3 days: Induction is performed according to local policy for induction of labor.~Comparison arm/expectant management: Waiting for spontaneous onset of labor unless a situation develops necessitating either induction of labor or caesarean section.~1900 low-risk pregnant women with a pre- or early pregnancy BMI ≥ 30 carrying a singleton pregnancy will be recruited from the Danish delivery wards. In each trial site, a physician investigator will be responsible for the enrolment, the electronically randomization, and data collection.~The primary endpoint is the caesarean section rate. Among others there will be secondary endpoints on instrumental delivery, onset of labor, methods of induction, perinatal and postpartum complications both maternal and neonatal along with data on women's experience on birth measured by a questionnaire survey four to six weeks post-partum.~Ethics The study will be conducted in accordance with the ethical principles outlined in the latest version of the 'Declaration of Helsinki' and the 'Guideline for Good Clinical Practice' related to experiments on humans. The Central Denmark Region Committee on Biomedical Research Ethics, and The Danish Health Authorities have approved the study.~Perspectives In perspective, more than 39% of the world's population is overweight and 13% are obese by the WHO classification. Pregnant overweight women are at increased risk of pregnancy and delivery complications, and there is a need to improve maternity care for this subgroup of women. The results of this trial have the potential to generate important knowledge for the improvement of delivery in obese women and they will add key information to an on-going discussion of the effects of labor induction before term. Any possible harm or disadvantage to the individual study participant is outweighed by the possible benefit to the increasing number of obese women who will be pregnant in the future.

The rate of overweight and obese women becoming pregnant is increasing. Obesity in pregnancy along with delivery by cesarean section in obese women is associated with several complications as compared to normal weight women. The longer the woman is pregnant, the longer she is at risk. In an otherwise low-risk pregnant woman at term, it is an ongoing clinical dilemma, whether the benefits of elective induction of labor and termination of the pregnancy will outweigh the potential harms from concomitant induction and delivery process. The proposed study is a randomized controlled study of elective induction versus expectant management in obese women. The study will be carried out as a national multicenter study with inclusion of 1900 participants from Danish delivery wards. The null hypothesis is that the caesarean section rate is similar with elective induction of labor at 39 weeks of gestation, compared with expectant management among pregnant women with pre- or early pregnancy BMI≥30.

This is a double-arm, single-center study. This study is indicated for relapsed and/or refractory B-cell acute lymphoblastic leukemia, B-cell non-Hodgkin's lymphoma and multiple myeloma, the selections of dose levels and the number of subjects are based on clinical trials of similar foreign products. 120 patients will be enrolled for this trial. Primary objective is to explore the safety.

A Study of CD19/BCMA-targeted CAR-T Cells Combined With Dasatinib for Patients With Relapsed and/or Refractory B-cell Acute Lymphoblastic Leukemia, B-cell Non-Hodgkin's Lymphoma and Multiple Myeloma.

The purpose of this basic research study is to determine the contribution of endogenous ascorbic acid (AA)turnover to urinary oxalate excretion in both normal BMI and obese adult non-stone formers and calcium oxalate stone formers. The studies proposed will use diets of known nutrient composition, a stable isotope of AA, 13C6-AA, and mass spectrometric techniques to quantify AA turnover to oxalate.~Adults (≥19 years) with and without a history of calcium oxalate kidney stone disease will be recruited from within the greater Birmingham area, and divided into normal BMI (BMI<25 kg/m2) and obese (BMI≥30 kg/m2) groups. Following consent, subjects will meet with a dietitian to ensure willingness to consume controlled diets, and provide fasted blood and 2 x 24 hour urine specimens to determine general health status and adequacy of 24-hour urine collections, respectively.~Eligible subjects will consume a low oxalate controlled diet for 6 days, which will involve 2 days of dietary equilibration followed by oral ingestion of 1 mg/kg carbon-13 AA with breakfast on day 3 and subsequent collection of 4 consecutive 24-hour urine specimens. After the carbon-13 AA load, subjects will return each morning to the Clinical Research Unit for a fasted blood draw, to drop off their 24-hour urine collection, and receive their prepared food. In addition, on day 4, 24 hours after ingesting carbon-13 AA, subjects will collect hourly urine and 1/2 hourly blood samples for 5 hours in the Clinical Research Unit.

The purpose of this basic research study is to determine the contribution of endogenous ascorbic acid (AA) turnover to urinary oxalate excretion in both normal BMI and obese adult non-stone formers and calcium oxalate stone formers. The studies proposed will use diets of known nutrient composition, a stable isotope of ascorbic acid (13C6-AA) and mass spectrometric techniques to quantify ascorbic acid turnover to oxalate.

This is a Phase 3, prospective, randomized, double-masked, two-arm, multi-center non-inferiority study evaluating the efficacy and safety of repeated intravitreal dosing of KSI-301 5 mg in participants with treatment-naïve DME.~The primary endpoint will be assessed at Year 1; additional secondary endpoints for efficacy will be assessed at Years 1 and 2.

This Phase 3 study will evaluate the efficacy, durability, and safety of KSI-301 compared to aflibercept in participants with treatment-naïve DME.

Migraine is a prevalent neurological disorder and a leading cause of years lived with disability worldwide. As of recent, therapies targeting calcitonin gene-related peptide (e.g. erenumab) have been approved for the preventive treatment of migraine. This study aims to investigate the effect of erenumab on efficacy outcomes, tolerability outcomes, and patient-reported outcomes in individuals with migraine. Furthermore, the study aims to identify clinical predictors of erenumab response.

This study aims to investigate the effect of erenumab on efficacy outcomes, tolerability outcomes, and patient-reported outcomes in individuals with migraine. Furthermore, the study aims to identify clinical predictors of erenumab response.

[Background]: In addition to Helicobacter pylori-negative gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (named as MALT lymphoma) (Sci Rep. 2017;7(1):14333), the investigators recently demonstrated that first-line antibiotics treatments can cure around 50% patients with stage IE/IIE1 extragastric MALT lymphoma (2018 ESMO poster discussion). However, the optimal management for antibiotics-unresponsive MALT lymphomas is not clearly defined.~[Rationale]: The investigators previously reported that thalidomide resulted in an overall response rate (ORR, including complete remission [CR] and partial remission [PR]) of 50% in 10 patients with antibiotics-unresponsive or chemotherapy-resistant MALT lymphoma. Lenalidomide (an immunomodulatory derivatives [IMiDs] of thalidomide) exhibits anti-angiogenic and immunomodulatory effects and has been proved efficacies in the treatment of multiple myeloma (MM). In the previous phase II study, single agent of lenalidomide resulted in ORR of 61.1% in 18 patients with MALT lymphoma. In addition to kill lymphoma cells, single low-dose cyclophosphamide, is an option for restoring immune response in patients with advanced cancer. The investigators also showed that low-dose cyclophosphamide (50 mg daily for 21 days, every 28 days) alone resulted in the ORR of 44.4 % in 9 patients with antibiotics-unresponsive MALT lymphoma. Previous studies also demonstrated that the addition of low-dose cyclophosphamide can overcome lenalidomide resistance in patients with MM.~[Hypotheses]: Considering that lenalidomide and cyclophosphamide are found to have anti-tumor effects in MALT lymphoma, the investigators speculated that combined lenalidomide and low-dose cyclophosphamide can increase the ORR rate as well as dural time of tumor remission, and avoid alternative treatments, including radiotherapy or chemotherapy-related adverse effects in antibiotics-unresponsive, relapsed or refractory extranodal MALT lymphoma.~[Methods]: Therefore, in this proposal, the investigators will design a prospective phase II study to evaluate the treatment efficacies of combination of oral lenalidomide and low-dose cyclophosphamide (LC: lenalidomide [Leavdo®] 15 mg daily, day 1 to day 21; cyclophosphamide [Endoxan] 50 mg daily, day 1 to day 21; courses will be repeated every 28 days) in patients with antibiotics-unresponsive, relapsed or refractory extranodal MALT lymphoma. The primary endpoint of this current study is ORR, and the second endpoint is adverse effect. The investigators will enroll 21 patients with antibiotics-unresponsive, relapsed or refractory MALT lymphoma based on the Simon minimax two-stage design.~The translational studies, including predictive markers and immunological profiles (BAFF-related canonical and non-canonical NF-κB signaling molecules, and immune-related molecules markers) will be included in the second points. The investigators will further assess immune-related molecules of nucleated cells of whole blood using flow cytometry, and analyze serum BAFF and cytokines.

Considering that lenalidomide and cyclophosphamide are found to have anti-tumor effects in MALT lymphoma, the investigators speculated that combined lenalidomide and low-dose cyclophosphamide can increase the overall response rate as well as dural time of tumor remission, and avoid alternative treatments, including radiotherapy or chemotherapy-related adverse effects in antibiotics-unresponsive, relapsed or refractory extranodal MALT lymphoma. Therefore, in this proposal, the investigators will design a prospective phase II study to evaluate the treatment efficacies of combination of oral lenalidomide and low-dose cyclophosphamide (LC: lenalidomide [Leavdo®] 15 mg daily, day 1 to day 21; cyclophosphamide [Endoxan] 50 mg daily, day 1 to day 21; courses will be repeated every 28 days) in patients with antibiotics-unresponsive, relapsed or refractory extranodal MALT lymphoma.

Despite advances in the clinical care of patients with DLBCL and in understanding the biology of this disease, cure rates have remained the same since the introduction of rituximab to CHOP chemotherapy, and R-CHOP chemoimmunotherapy remains the standard of care. Over the last years many phase III trials investigating new agents added to R-CHOP have been performed but they have all invariably failed to improve treatment outcomes. Importantly, three of the most recently completed phase III trials that were developed based on the cell of origin distinction of DLBCL and aimed to improve treatment outcome in the ABC (or non- Germinal center B-Cell (GCB)) subtype by adding a targeted agent to R-CHOP have also failed. This provides clinical evidence that cell of origin may not be an accurate biomarker for treatment decisions. The R - CHOP + investigational drug approach has thus failed either when broadly applied to unselected DLBCL patients or when applied to DLBCL patients selected according to inaccurate biomarkers such as COO.~Within this exploratory multicohort phase II trial, SAKK aims to evaluate a PET/CT and ctDNA oriented therapy in DLBCL in order to test the following working hypothesis.~acalabrutinib-R-CHOP may improve the progression free survival in genetically defined DLBCL harboring the MYD88 L265P and/or CD79A/B mutations;~treatment escalation to acalabrutinib-R-CHOP in DLBCL patients who have positive PET/CT (with residual disease scored as Deauville score 4 or 5 with centrally defined response) and no molecular response (<2log10 reduction of ctDNA) after two courses of R-CHOP could improve the anti-tumour activity of R-CHOP;~treatment de-escalation to 4 total R-CHOP courses plus 2 rituximab single agent infusions does not compromise the outcome in patients lacking both MYD88 L265P and CD79A/B mutations and quickly obtaining both negative PET/CT (Deauville score 1-3) and molecular response (>2log10 reduction of ctDNA) after two courses R-CHOP.~Primary objectives:~Assessing the efficacy of acalabrutinib-R-CHOP in DLBCL harboring MYD88 L265P and/or CD79A/B mutations (cohort A)~Assessing the activity of treatment escalation to acalabrutinib-R-CHOP followed by acalabrutinib monotherapy in DLBCL patients who are double positive: PET/CT positive (Deauville score 4 or 5 with centrally defined response) and no molecular response (<2log10 fold reduction) after two courses of R-CHOP (cohort B)~Exploring the feasibility of treatment de-escalation to 4 total R-CHOP courses plus two infusions of single agent rituximab in patients lacking both MYD88 L265P and CD79A/B mutations and quickly obtaining both negative PET/CT (Deauville score 1-3) and molecular response (>2log10 reduction of ctDNA) after two cycles of R-CHOP (cohort C).~Exploring clinical implications of having a negative PET/CT (Deauville score 1-3) but no molecular response (<2log10 reduction of ctDNA) vs a positive PET/CT (Deauville score 4 or 5 with centrally defined response) but molecular response (>2log10 reduction of ctDNA) after two R-CHOP courses (cohort D)~Secondary objectives:~Safety and tolerability of acalabrutinib-R-CHOP~Assessment of prognostic value of baseline PET radiomics indexes, alone or in association with other parameters

Within this exploratory multicohort phase II trial, SAKK aims to evaluate a PET/CT and ctDNA oriented therapy in DLBCL in order to test the following working hypothesis.~acalabrutinib-R-CHOP may improve the progression free survival in genetically defined DLBCL harboring the MYD88 L265P and/or CD79A/B mutations;~treatment escalation to acalabrutinib-R-CHOP in DLBCL patients who have positive PET/CT (with residual disease scored as Deauville score 4 or 5 with centrally defined response) and no molecular response (<2log10 reduction of ctDNA) after two courses of R-CHOP could improve the anti-tumour activity of R-CHOP;~treatment de-escalation to 4 total R-CHOP courses plus 2 rituximab single agent infusions does not compromise the outcome in patients lacking both MYD88 L265P and CD79A/B mutations and quickly obtaining both negative PET/CT (Deauville score 1-3) and molecular response (>2log10 reduction of ctDNA) after two cycles of R-CHOP.

The study comprises three open-label substudies in patients with HER2-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring FGFR2 gene translocations, FGFR2 gene amplifications, or FGFR1-3 mutations. Patients will be treated with single-agent derazantinib or derazantinib in combination with paclitaxel, ramucirumab, or atezolizumab. The study enrolls patients with either metastatic or recurrent locally advanced HER2-negative adenocarcinoma of the stomach or gastro-esophageal junction inoperable at the time of screening, and radiologically confirmed disease progression after one or at least one standard treatment regimen.

The purpose of this study is to evaluate the efficacy of derazantinib monotherapy or derazantinib in combination with paclitaxel, ramucirumab, or atezolizumab in patients with HER2-negative adenocarcinoma of the stomach or gastro-esophageal junction harboring FGFR2 genetic aberrations (GA).

Endodontically treated teeth commonly present with extensive tooth structure loss due to caries, trauma, prior restorative treatment, and the endodontic access. These structural deficiencies lead to an increase in cusp deflection, crown fractures, microleakage, and decreased sensory feedback during function which greatly increases the possibility of tooth fracture.As a result, endodontically treated teeth require a full cuspal coverage restoration to prevent microleakage, restore function, and provide cuspal protection against tooth fracture. The most common restoration for endodontically treated teeth is core build-up, with or without a post, and full coverage crown.~This process requires multiple appointments with many technical steps ultimately leading to more chair time, treatment cost, and potential iatrogenic damage to the tooth. An alternative treatment is the endocrown, which utilizes the internal walls of the pulp chamber for macroretention and incorporates the core and crown in a monolithic restoration. The restoration is fabricated utilizing chairside CAD/CAM technology and is adhesively bonded to the tooth with resin cement. The EndoCrown restoration is more conservative relative to tooth structure loss, less expensive, and requires less chair time to complete when compared to conventional treatment while having comparable clinical longevity in molar teeth.~This investigation will be a longitudinal clinical trial to study the association of preparation design on the internal and marginal adaptation of the resulting restorations and the long-term clinical performance of chairside CAD/CAM endocrown restorations. Advanced lithium disilicate chairside CAD/CAM endocrowns (CEREC Tessera/Dentsply Sirona) will be adhesively bonded using a selective enamel etch technique with a universal adhesive (Prime and Bond Elect/Dentsply Sirona) and a dual cure resin adhesive cement (Calibra Ceram/Dentsply Sirona). All restorations will be followed over five years of clinical service.

This investigation will be a longitudinal clinical trial to study the association of preparation design on the internal and marginal adaptation of the resulting restorations and the long-term clinical performance of chairside CAD/CAM endocrown restorations. Advanced lithium disilicate chairside CAD/CAM endocrowns (CEREC Tessera/Dentsply Sirona) will be adhesively bonded using a selective enamel etch technique with a universal adhesive (Prime and Bond Elect/Dentsply Sirona) and a dual cure resin adhesive cement (Calibra Ceram/Dentsply Sirona). All restorations will be followed over five years of clinical service.

Cerebral amyloid angiopathy (CAA) involves amyloid deposition in the vessel walls in the cerebral cortex and overlying leptomeninges, causing symptomatic intracerebral lobar intracerebral hemorrhage (ICH) in the elderly. CAA is considered as a form of cerebral small vessel disease, which refers to a group of vascular pathologies that affect the small vessels of the brain. In addition to lobar ICH, patients may present with other parenchymal injuries that can be detected on blood-sensitive MRI, such as multiple strictly lobar cerebral microbleeds, cortical superficial siderosis and leukoariosis. Recently, CAA has been suggested in association with MRI-visible enlarged perivascular space (EPVS) in centrum-semiovale (CSO), contrary to more severe MRI-visible EPVS in basal ganglia that is frequently found in chronic hypertension. The dilated perivascular space in CAA is suggestive of chronic poor perivascular drainage of the leptomeningeal arteries, predisposing individuals to impaired or altered meningeal lymphatic drainage and causing defect in amyloid clearance and subsequent CAA development. Nevertheless, it is unknown whether lymphatic drainage are the main routes for vascular amyloid clearance, and its relationship to the long-term outcome has not been clearly investigated in clinical patients yet.~In this three-year proposal, we will explore the MRI-visible EPVS in CAA and investigate its pathophysiology using animal models. Our specific aims include: (1) Establish the relationship of MRI-visible enlarged perivascular space and CAA, (2) Determine whether vascular amyloid clearance in CAA is associated with lymphatic drainage system, (3) Establish longitudinal data for MRI-visible enlarged perivascular space and cerebral amyloid angiopathy progression. In the first year, we will recruit spontaneous ICH patients for brain MRI, in vivo amyloid imaging and measuring their plasma Aβ40/42 levels. We aim to confirm EPVS in CSO as a specific marker for CAA, and to provide direct evidence that dilated perivascular space is worse with more advanced CAA; For the second year, we plan to use transgenic CAA mouse models to confirm that meningeal lymphatic drainage routes are crucial for clearance of vascular amyloid-β. We will manipulate the lymphatic drainage routes by either blockage or enhancement of the lymphatic vessels, to see if the vascular amyloid clearance is affected; For the third year, the main research focus will on be establishing the longitudinal data on amyloid and tau deposition in clinical ICH patients. We plan to repeat in vivo amyloid imaging in 2 years, for the purpose of validating our hypothesis in human that baseline worse lymphatic drainage function is associated with quicker cerebral vascular amyloid progression or prediction of future CAA development. We will also recruit patients for in vivo tau imaging to investigate long-term neuronal injury and neurodegeneration, namely tau-mediated neurofibrillary tangle, in relation to the impaired perivascular drainage in CAA.

In this three-year proposal, we will explore the MRI-visible EPVS in CAA and investigate its pathophysiology using animal models. Our specific aims include: (1) Establish the relationship of MRI-visible enlarged perivascular space and CAA, (2) Determine whether vascular amyloid clearance in CAA is associated with lymphatic drainage system, (3) Establish longitudinal data for MRI-visible enlarged perivascular space and cerebral amyloid angiopathy progression.

Background and objectives Owing to the aging problem, cognitive impairment has been a worldwide health issue. Vascular cognitive impairment (VCI) and Alzheimer's disease (AD) are the two most common causes. It has been reported that VCI and AD share many common risk factors. MRI is essential in assessing the extent, location and type of vascular lesions. Amyloid PET has been used in detecting cerebral amyloid burden non-invasively since 2004. There are only small number of studies using amyloid PET in VCI and the results are still controversial. In the current proposal, we will investigate~the correlation of clinical risk factors, ApoE genotype, various MRI markers, and amyloid PET expression~assess the influence of ApoE genotype on different biomarkers, including MRI markers, amyloid retention, and plasma Aβ40 and Aβ42 levels~the potential of amyloid PET as a prognostic factor for VCI patients.~Materials and methods This study will be conducted in National Taiwan University Hospital and Bei-Hu Branch Hospital. Sixty clinical diagnosed VCI, 30 AD patients and 30 normal subjects will be enrolled in this 3-year prospective study. We will collect vascular risk factors, neuropsychological tests, 10 cc venous blood for plasma Aβ40, Aβ42, total tau and phosphorylated level measurement by IMR assay, ApoE genotype, brain MRI, and amyloid PET of each patient and control subject. All the data will be analyzed together.~Expected Results We will try to~establish the correlation of plasma Aβ40 and Aβ42 level, ApoE genotype, MRI imaging markers in the diagnosis and prognosis of VCI patients~understand more on the pathophysiology of VCI.

We will try to~establish the correlation of plasma Aβ40 and Aβ42 level, ApoE genotype, MRI imaging markers in the diagnosis and prognosis of VCI patients~understand more on the pathophysiology of VCI.

The researchers will treat 40 patients with metformin (1500 mg/day) and LDN (4.5 mg/day) for 4 weeks to reduce symptoms, disease severity, and recovery time from COVID-19. These 40 patients will be compared with 40 control patients who will receive regular care. All patients will be asked to complete surveys at baseline and after 1, 2, and 4 weeks after initiation of treatment. The difference with baseline at each time point will be assessed. The surveys will assess COVID-19 symptoms severity.

Study into the effects of daily use of metformin and low-dose naltrexone (LDN) for 4 weeks to reduce symptoms, disease severity, and recovery time from COVID-19.

This interventional pilot study will assess the use of low dose naltrexone (LDN) and NAD+ for the treatment of patients with post-COVID-19 syndrome (long-COVID-19).~Patients with a positive test for SARS-CoV-2 1-4 months before enrollment will be included. Subjects should have self diagnosed post-COVID19 syndrome and experiencing persistent fatigue since positive test. Patients will be screened using the fatigue survey and cases with a moderate to severe score will be included.~Patients will receive LDN and NAD+ treatment for 12 weeks. In this study, fatigue and quality of life will be assessed using validated surveys. Surveys will be conducted at baseline (at the time of enrollments, before treatment), and at 2, 4, 8, and 12 weeks. The improvement of scores from baseline levels will be assessed.

Pilot study into low dose naltrexone (LDN) and NAD+ for treatment of patients with post-COVID-19 syndrome.

This study is designed to be a multicentre, prospective, comparative, randomised trial, evaluating the efficacy of two surgical strategies for the treatment of generalised peritonitis due to perforated diverticulitis. Results will be analysed according to an intention to treat principle. The diagnosis will be established by the surgeon investigator on clinical data, imagery and operative findings during a laparotomy or laparoscopy. After selection and patient consent and immediately before surgery, the patient will be randomly assigned to sigmoidectomy with primary anastomosis or to sigmoidectomy with primary anastomosis and diverting stoma. Sigmoidectomy will be performed through a midline laparotomy or laparoscopically according to the standard technique, with lateral to medial mobilisation of the left colon, mobilisation of splenic flexure and identification of left ureter. The rectosigmoid junction will be exposed and transected with a stapler. Proximal section will be performed on a healthy colonic segment. The anastomosis will be performed according to the surgeon investigator's preference (mechanical or manual anastomosis; end to end or side to end).~Decisions to clean the colon intraoperatively and to place a drain will be left to the surgeon's discretion. In the control arm, a protective stoma will be performed at the end of surgery. A stoma reversal operation will be performed at least 3 months after the first operation and after performing a cologram by water soluble contrast between 4 and 8 weeks to check for the absence of fistula or stenosis at the level of the anastomosis. Stoma reversal will be performed with a trephine incision.~Post-stoma closure follow-ups will be planned and all morbidity/mortality will be recorded. All patients will be examined at 6, 12, and 24 weeks after the initial surgery, in the surgical department where they were operated; a final study visit will be carried out 12 months (evaluation of primary endpoint) after surgery. The parameters explored at medical examinations will be: • Occurrence of complications • Quality of life assessment

This study is designed to be a multicentre, prospective, comparative, randomised trial, evaluating the efficacy of two surgical strategies for the treatment of generalised peritonitis due to perforated diverticulitis. Results will be analysed according to an intention to treat principle (after selection and patient consent). Immediately before surgery, the patient will be randomly assigned to sigmoidectomy with primary anastomosis or to sigmoidectomy with primary anastomosis and diverting stoma. Sigmoidectomy will be performed through a midline laparotomy or laparoscopically according to the standard technique. In the control arm, a protective stoma will be performed at the end of surgery. A stoma reversal operation will be performed at least 3 months after the first operation and after performing a cologram by water soluble contrast between 4 and 8 weeks to check for the absence of fistula or stenosis at the level of the anastomosis. Stoma reversal will be performed with a trephine incision.~Post-stoma closure follow-ups will be planned and all morbidity/mortality will be recorded. All patients will be examined at 6, 12, and 24 weeks after the initial surgery, in the surgical department where they were operated; a final study visit will be carried out 12 months (evaluation of primary endpoint) after surgery. The parameters explored at medical examinations will be: • Occurrence of complications • Quality of life assessment

Well-being of caregivers and stress management in intensive care units are essential keys to an adequate quality of care, especially during the anxious context of coronavirus pandemic. Taking care of numerous patients, the increasing work and mental charges, facing death, the need of material and changes in work organization are all elements that can influence stress among medical workers. Considering real causes of stress and what are the needs of the medical team is fundamental for developing concrete actions to ease the workloads. A few studies were conducted in China on psychological distress of medical staff during COVID-19. According to these few studies about psychological distress in ICU, investigators think that stress scores during COVID-19 could be increased among nurses during pandemic. The second hypothesis is that causes of stress would be not so different from normal care but could be amplified by the actual situation. One point to take into consideration is that most of the studies were conducted in China and medical policy and hospital organization are different in Belgium. The objective of the study is to compare psychological distress and needs of nurses in ICU before and during coronavirus pandemic.

The objective of this study is to compare psychological distress and needs of nurses in ICU before and during coronavirus pandemic.

This is a multi-centre, open-label, single-dose safety, tolerability and PK-pharmacodynamics (PD) study of the vasodilator regadenoson in 3 paediatric age groups for whom a pharmacologic stress perfusion CMR test is clinically indicated; adolescents aged 12 to <18 years (Cohort A), children aged 2 to <12 years (Cohort B), and infants aged 1 to <24 months and who weigh at least 3 kg (Cohort C). Regadenoson will be used as the pharmacologic stress agent in this study with MPI serving as both surrogate pharmacodynamic marker of the agent (MPR, MBF) and a clinically evaluable examination for the patient.~At least 54 paediatric patients will be enrolled at approximately 10 centres in Europe: at least 24 adolescents aged 12 to <18 years (Cohort A), at least 18 children aged 2 to <12 years (Cohort B), and at least 12 infants aged 1 to <24 months (Cohort C). The study will be conducted in facilities appropriate for children, and by personnel knowledgeable and skilled in working with paediatric patients. Every attempt will be made to minimise the discomfort of the procedures to the patients. General anaesthesia/sedation with no oral-intake instructions may be used in accordance with age / disease specific requirements of the patient and as deemed necessary by the investigator per standard of care / local practice. In addition, adequate resuscitation equipment and personnel trained and certified in advanced life support must be readily available when regadenoson is administered. A Data Safety Monitoring Board (DSMB) will be in place, and will formally review all safety, efficacy, PK and PD information during the conduct of the study to ensure the safety of patients.~The study will be performed in a sequential manner across the 3 age groups, by decreasing age from adolescents (Cohort A) to children (Cohort B) and to infants (Cohort C). Dosing recommendations for the paediatric population are based on effective dose levels and PK data in adults. Based on a fixed dose of 400 µg regadenoson administered to adults with a mean body weight of 83.8 kg (body weight range: 42 to 161 kg), the effective mean weight-based dose was 4.8 µg/kg (range: 2.5 to 9.5 µg/kg). Within each age group, dosing will be extrapolated from PK-PD data obtained in adults and will be based on body weight-categories to provide approximately the same exposure as 400 µg in adults. The study will start with Cohort A (adolescents). Before the start of dosing in Cohort B, all safety, PK, and PD data obtained in Cohort A will be reviewed by the DSMB. Before the start of dosing in Cohort C, all safety, PK, and PD data obtained in Cohorts A and B will be reviewed by the DSMB.

This is a multi-centre, open-label, single-dose safety, tolerability and PK-pharmacodynamics (PD) study of the vasodilator regadenoson in 3 paediatric age groups for whom a pharmacologic stress perfusion CMR test is clinically indicated; adolescents aged 12 to <18 years (Cohort A), children aged 2 to <12 years (Cohort B), and infants aged 1 to <24 months and who weigh at least 3 kg (Cohort C). Regadenoson will be used as the pharmacologic stress agent in this study with MPI serving as both surrogate pharmacodynamic marker of the agent (MPR, MBF) and a clinically evaluable examination for the patient

This is a prospective, multi-center, single arm, Phase 2 study of human retinal progenitor cells (jCell) for the treatment of retinitis pigmentosa (RP). The study will include only subjects previously treated with jCell.~To assess reinjection of a previously treated eye, subjects who have previously been treated with jCell and desire a second treatment in the same eye will be enrolled. Subjects must have completed at least 12 months of follow up since the prior injection of jCell. Subjects who have had both eyes previously treated with jCell will only have one eye retreated; the eye to be retreated will preferably be the better seeing eye, but exceptions may be made by the study investigator, taking into consideration BCVA, prior response to treatment, and any other medical conditions that may indicate which eye is the best candidate for retreatment. Subjects will be followed for 12 months for safety and efficacy.

The primary objective of the study is to assess the safety of repeat injection of human retinal progenitor cells (jCell) in adult subjects with RP that have previously been treated with jCell.

Investigators at Northwestern University will partner with Omron Healthcare Co., Ltd. (hereinafter referred to as Omron) to conduct a pragmatic pilot test of a remote patient monitoring system (RPM) for blood pressure measurement for Medicare patients with hypertension. The primary objective is to better understand how patients' remote monitoring of blood pressure and the direct transmission of this data to a healthcare system's EHR can be used by the patient and the care team to support optimal hypertension care. The procedures that will be evaluated are routine healthcare services that are currently reimbursable by Medicare. However, the optimal ways to: integrate these tools into primary care practice, promote clinician and patient uptake, and put this information to use in the clinical environment to best control hypertension are not fully understood. This pilot study which we will conduct in two Northwestern Medical Group (NMG) primary care practices will: evaluate the integration of Omron's remote monitoring system into Northwestern Medicine's electronic health record (so that clinical data can flow directly from the patient's monitor to the EHR), evaluate the use of billing work flows for covered Medicare services, build and deploy clinical decision support to aid with patient identification and ordering of the remote patient monitoring system, and evaluate the uptake and clinical effects of this system in the pilot practices compared to matched patients selected from non-pilot control practices.~The remote patient monitoring (RPM) system will be provided by Omron Healthcare to eligible patients at no charge. This will include a Bluetooth enabled home blood pressure monitor, a simplified smart phone connected to the Verizon network and, if requested, a Bluetooth enabled scale. Patients who are agreeable to using this RPM system will have this service ordered by their clinician will have this equipment mailed to their homes. Payments for reimbursable remote monitoring services will be billed by Northwestern Medicine to Medicare and supplemental insurance coverage in the fashion that is permitted under Medicare rules.~The investigators will conduct a pragmatic non-blinded, non-randomized pilot study with contemporaneous controls among NMG outpatient clinics that provide adult primary care. We will make comparisons of data obtained through the course of routine care delivery from pilot and non-pilot practices.

The investigators will conduct a pragmatic pilot test of a remote patient monitoring system (RPM) for blood pressure measurement for Medicare patients with hypertension. The primary objective is to better understand how patients' remote monitoring of blood pressure and the direct transmission of this data to a healthcare system's EHR can be used by the patient and the care team to support optimal hypertension care.~This pilot study which we will conduct in two Northwestern Medical Group (NMG) primary care practices will: evaluate the integration of Omron's remote monitoring system into Northwestern Medicine's electronic health record (so that clinical data can flow directly from the patient's monitor to the EHR), evaluate the use of billing work flows for covered Medicare services, build and deploy clinical decision support to aid with patient identification and ordering of the remote patient monitoring system, and evaluate the uptake and clinical effects of this system in the pilot practices compared to matched patients selected from non-pilot control practices.~The investigators will conduct a pragmatic non-blinded, non-randomized pilot study with contemporaneous controls among NMG outpatient clinics that provide adult primary care. They will make comparisons of data obtained through the course of routine care delivery from pilot and non-pilot practices.

For decades, clinicians and scientists have focused on finding a cure for paralysis. However, research has shown that individuals with SCI more highly prioritize bladder, bowel and sexual functioning over the ability to walk again. There is still a major lack of research towards improving these critical components of autonomic recovery following SCI. This clinical study examines the EFFECTS OF TRANSCUTANEOUS SPINAL CORD STIMULATION (TCSCS) in promoting recovery of bladder, bowel and sexual functions in individuals with SCI. This NON-INVASIVE THERAPEUTIC METHOD utilizes electrodes applied over the skin, and is based on ground-breaking work (from the investigator's group and others), showing that spinal cord stimulation can promote motor and autonomic recovery in individuals with chronic SCI. This study is a collaborative effort between clinicians and scientists with expertise in: SCI care, rehabilitation, bladder, bowel, cardiovascular and sexual functioning.~Safety will be routinely monitored. Six weeks after completion of stimulation experiments, bladder, bowel and sexual function will be reassessed to examine the longevity of TCSCS-induced effects. TCSCS COULD OFFER A SIMPLE, COST-EFFECTIVE SOLUTION TO TREAT AUTONOMIC DYSFUNCTIONS (i.e. urine and faecal incontinence, erectile difficulties etc.) that would undoubtedly significantly improve overall health related quality of life for individuals with SCI.~Recent findings have demonstrated that electrical stimulation to the spinal cord (i.e. implanted electrodes) can significantly recover bladder, bowel, and sexual function after injury. While promising, a major drawback is that individuals must undergo a highly invasive and expensive surgical procedure to implant the stimulator on top of the spinal cord. Moreover, the inability to re-position the implanted stimulator considerably limits the flexibility of this procedure.~In this project, the investigators propose a comprehensive clinical study examining the effects of TCSCS in promoting recovery of these crucial functions in individuals with SCI. This non-invasive therapeutic modality uses electrodes applied over the skin to deliver electrical stimulation. It is based on the same principles of ground-breaking work from the investigator's group and others, showing that stimulation of the spinal cord can promote motor and autonomic (cardiovascular, bladder, bowel) recovery in individuals with chronic SCI.~Electrical neuromodulation has recently emerged as a leader in potential therapies for restoring voluntary control of functional movements in lower limbs after SCI. In addition to functional motor recovery, numerous studies from the investigator's group and collaborators have shown efficacy of both epidural stimulation (invasive) and non-invasive stimulation (TCSCS) in restoring autonomic function. For example, in the investigators preliminary examination of several individuals with SCI, the investigators have demonstrated that epidural stimulation acutely restores cardiovascular control, improves lower urinary tract (LUT) function and reduces time needed for bowel routine. These studies were highly influential in developing stimulation protocols and establishing spinal cord stimulation as a safe and effective therapy. The next logical step is to conduct a wider-scale clinical trial for TCSCS as a novel, efficacious and inexpensive alternative therapy to epidural stimulation. By uniting experts in the field of SCI, physical medicine/rehabilitation, urology, colorectal health and sexual functioning, the investigators are well-equipped to assess TCSCS as a novel means of improving recovery of LUT, bowel and sexual function. The investigator's team has a strong history of collaborative research in these fields and extensive experience in the evaluation of these three aspects of autonomic function using physiological measures/clinical assessments in addition to well-validated questionnaires.~The investigators anticipate that individuals with SCI who participate in this trial will receive a therapeutic benefit in at least one of the multiple outcomes (i.e. LUT, bowel and sexual function) and will also obtain greater insight into the nature of their current health status in these areas post-SCI. This project will also have a high degree of impact on the SCI-community by further developing TCSCS as a more accessible and inexpensive therapy for autonomic dysfunctions. Ultimately the investigator's goal is to improve quality of life for individuals with SCI, which the investigators anticipate in turn will decrease caregiver burden and health care costs due to LUT, bowel and sexual issues associated with SCI.~Eligible individuals who sign the consent form will first undergo screening and initial evaluations (total of 6 visits completed within 6 weeks) and then will be randomly assigned to either a moderate TCSCS treatment group (2 days/week for a total of 12 treatment sessions) or intense TCSCS treatment group (5days/week for a total of 30 treatment sessions) during the 6 weeks treatment period. After completion of total protocol, each participant will undergo 4 follow up assessments that will be completed within 12 weeks following the treatment. Overall, the total duration of participation will be approximately 25 weeks.~Visit 1 Screening Approximately 1.5 hours After a participant has provided informed consent, he/she will be assigned a unique study number will be invited for a screening assessment to confirm study eligibility.~Visit 2: Baseline Assessments Approximately 1 hour. All eligible participants will be guided through a series of questionnaires on bladder function, bowel function, cardiovascular function and sexual health (outcomes 6-10 below). Participants will also undergo baseline 24 hours ambulatory evaluation of cardiovascular functions (outcome 1).~Visit 3 /Baseline EMG Mapping of Spinal Cord Segments with TCSCS Approximately 2 hours. Participants will undergo baseline mapping using surface EMG and concentric needle EMG as per an established protocol to record muscle activation during transcutaneous spinal cord stimulation (mapping) at different spinal cord levels and different intensity (outcome 2).~Visits 4,5 and 6: Bladder and bowel function assessment procedures with and without non-invasive transcutaneous spinal cord stimulation Approximately 2.5 hours per visit.~Visits 4, 5, and 6 will include assessments of bladder function (urodynamics, outcome 3) and bowel function (Anorectal Manometry, outcome 4). Bladder assessments will take place at the Blusson Spinal Cord Centre and bowel assessments will take place at St. Paul's Hospital.~The order of these 3 visits will differ randomly between individuals and will be one of the following:~Pathway #1: you will start with Urodynamics, (UDS 1, Visit 4), followed by a second session of Urodynamics (UDS 2, Visit 5), followed by bowel function assessments(Visit 6).~Pathway#2: you will start bowel function assessments (Visit 4), followed by Urodynamics (UDS 1, Visit 5), and a second session of Urodynamics (UDS 2, Visit 6)).~Visits 7-18 or 36: Long Term Non-invasive transcutaneous spinal cord stimulation Approximately 1.5 hours per visit.~Participants will be asked to come to ICORD for TCSCS either 2 days/week (moderate treatment group with total 12 treatment sessions) or 5 days/week (intense treatment group with total 30 treatment sessions) for 6 weeks. Participants will be randomly assignment to either the moderate or intense treatment groups. Whether a participant are assigned to the moderate or intense group will be determined by chance (like the flip of a coin). Each TCSCS session will last approximately 90 minutes. Stimulation will be applied for a total of 60 minutes in three 20-minute intervals with 2 minute breaks. Skin temperature, blood pressure and heart rate will be monitored. Mid-way through the 6 weeks, participants will be set up with an ambulatory blood pressure monitor to wear at home on the day of the participant's bowel routine. We will also provide a diary for participants to log their activities while wearing the blood pressure monitor.~Visit 19 or 37: Bladder assessment and SCI severity assessment - Approximately 3 hours~After the 6 weeks of TCSCS, a third urodynamics assessment will be performed at the Blusson Spinal cord centre, following the same procedure described above, both without and with TCSCS. During this visit, a clinician will also perform a SCI severity assessment (International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) exam).~Visit 20 or 38: Immediate Follow up Telephone Questionnaires - Approximately 1 hour~Visit 20 or 38 will take place by telephone or video conference call (considering the present COVID-19 pandemic environment). Participants will be guided through the same series of questionnaires as in visit 1 and 2, on bladder function, bowel function, cardiovascular function and sexual health.~Visits 21-22 or 39-40: Long Term follow up Telephone Questionnaires and Semi Structured Interview:~Approximately 1 hour (visit 21/39) and approximately 1.5 hours (visit 22/40)~These visits will take place over the telephone to evaluate existing and new adverse events and concurrent treatments. During each of these follow-up phone Visits (39 and 40) at 6 and 12 weeks post completion of long term TCSCS, participants will be guided through the same series of questionnaires on bladder function, bowel function, cardiovascular function and sexual health described above.~During visit 22 or visit 40, a sexual health clinician, with experience providing clinical care to individuals with SCI, will also conduct a semi-structured qualitative interview (outcome 11) during which they will ask participants questions about the following: sexual history and current relationship status, level of sexual drive, ability to orgasm, barriers to sexual activity, self-esteem, the use of performance enhancing aids, and the participant's perceptions of the role of TCSCS on sexual functioning.

Recent findings have demonstrated that electrical stimulation to the spinal cord (i.e. implanted electrodes) can significantly recover bladder, bowel, and sexual function after injury. While promising, a major drawback is that individuals must undergo a highly invasive and expensive surgical procedure to implant the stimulator on top of the spinal cord. Moreover, the inability to re-position the implanted stimulator considerably limits the flexibility of this procedure.~In this project, the investigators propose a comprehensive clinical study examining the effects of TCSCS in promoting recovery of these crucial functions in individuals with spinal cord injury (SCI). This non-invasive therapeutic modality uses electrodes applied over the skin to deliver electrical stimulation. It is based on the same principles of ground-breaking work from the investigator's group and others, showing that stimulation of the spinal cord can promote motor and autonomic (cardiovascular, bladder, bowel) recovery in individuals with chronic SCI.

Type of study: RCT~Review of literature:~Different modalities of urethroplasty for repair of proximal hypospadias with chordee (two-stage repair, one-stage repair, flap, graft).~Disadvantages of two-stage urethroplasty for proximal hypospadias with chordee..~Merits of one-stage urethroplasty for proximal hypospadias with chordee. This is a prospective randomized controlled study conducted at pediatric surgery department, Al-Houssain & New Damietta Al-Azhar University Hospitals, from March 2014 to March 2020, on 144 male patients with penoscrotal hypospadias with chordee. Patients will be investigated by routine laboratory tests for fitness for surgery. All of them will undergo one-stage repair using either of 2 techniques of tubularized preputial flap; Duckett's versus DFPF. Written informed consent will be obtained from parents of all participants in the study.~Institutes of the study:~A multicenter study at Pediatric Surgery Departments, Al-Azhar University hospitals in Cairo and New Damietta. Number of cases: One-hundred-Forty four male patients. Time frame: period of 6 years.~Ethical Consideration:~The protocol will be discussed and approved for clinical study by the Ethical Research Committee at the principal investigator's hospital. The procedures and the aim of the study will be clearly explained to the patient and the family. A written informed consent will be obtained before enrollment of the patients into the study. The family refusal to give consent for one-stage repair is respected but does not deprive the patient from getting surgical care by two-stage repair.~Preoperative preparation:~All patients will be subjected to history taking, clinical examination, and necessary laboratory investigations (CBC, Coagulation profile, Liver and Renal Function tests, Electrolytes Panel, Urinalysis). They will receive a dose of single broad-spectrum antibiotic 30 min-1 hour before surgery. Patients will be randomly divided (using the computer-generated randomization table) into two equal groups, each will include 72 patients; Group I will undergo transverse preputial island flap (Duckett's technique) and Group II will undergo double-faced preputial flap (DFPF). Both techniques will be done by all members of the surgical team equally.~Follow-up:~Patients will be followed-up at OPD.~Statistical Analysis:~Data were collected using a data collecting sheets (annexes) and were analyzed using the statistical package for social sciences (SPSS) version 24.0 (IBM SPSS Statistics for Windows, IBM Corp, Armonk, NY, USA). Continuous variables were expressed as mean±standard deviation (SD), range, and average and categorical variables were expressed as frequency count & percentage. Fisher's exact test was used for comparison of frequency counts/percentage. A two-sided p-value < 0.05 was considered statistically significant.~Discussion:~It will focus on one-stage urethroplasty using the preputial flap for proximal hypospadias with chordee. The results obtained from this study will be compared between both group and with those reported in the literature.~Also, it will focus on results, complications, their management, and clinical evaluation by estimated urine caliber and micturition time. At the end, the investigators will conclude the reconstructive technique that gives the better results and least morbidity.

The purpose of this study is to compare the outcomes and complications of the transverse preputial island flap (Duckett's procedure) to those of double-faced preputial flap (DFPF) for one-stage repair of penoscrotal hypospadias with chordee, in addition to clinical functional evaluation by estimated urine flow.

The aim of this study is to investigate the use of benralizumab as treatment for patients with moderate to severe atopic dermatitis (AD) who remain symptomatic despite treatment with topical medications. It is proposed that benralizumab will deplete eosinophils from affected skin, improve symptoms of AD, and improve AD-related quality of life. This Phase 2 study is designed to compare the efficacy of treatment with benralizumab versus placebo and compare benralizumab maintenance dosing regimens in the extension period.

The purpose of the study is to compare the efficacy and safety of benralizumab versus placebo and to compare benralizumab dosing regimens during extension period.

Cervical and lumbar fusion are often the best option for various degenerative conditions that do not respond to conservative treatment. Historically, the reference technique for cervical fusion was the use of iliac crest autogenic bone graft (ICBG). However, the use of ICBG has several drawbacks, including the morbidity of the donor site, the increase in operating time and the variable quality of autograft. Alternatives to ICBG for cervical fusion include the use of allografts, graft extensions and osteobiological materials to improve fusion rates.~This is a prospective, single arm, single center clinical study to evaluate efficacy and safety of a Supercritical CO2 viral-inactivated allogenic bone paste in cervical interbody fusion. Patient eligible for 1- or 2-level ACDF (Anterior Cervical Discectomy and Fusion) combined with bone graft after failure of well-conducted medical treatment will be screened for the study.~Subjects will be followed up postoperatively per standard of care at 3 months, 6 months, 12 and 24 months at the clinic. The following outcomes will be measured: overall success, Neck Disability Index (NDI), VAS neck and arm pain, SF-12 health survey, major complications, subsequent surgery rate, and fusion rate on radiological examinations. The primary endpoint is a FDA composite definition of success comprising clinical improvement and absence of major complications and secondary surgery events.

This is a prospective, single arm, single center clinical study to evaluate efficacy and safety of a Supercritical CO2 viral-inactivated allogenic bone paste in cervical interbody fusion. Patient eligible for 1- or 2-level ACDF (Anterior Cervical Discectomy and Fusion) combined with bone graft after failure of well-conducted medical treatment will be screened for the study.

After being informed about the study and potential risks, all patients give written informed consent. Thereafter, patient will get calcium electroporation with biopsies and digital photographs on day 0. We expect to discharge all patients same evening. Between day 3-7 an examination is followed by gastroscopy with biopsies and digital photographs. On day 14 the patients are followed in our outpatient clinic. 6 weeks after treatment the patients will undergo endoscopic mucosa resection (EMR) or endoscopic submucosa dissection (ESD) surgery and thereby the standard care of treatment for Barrett's esophagus high-grade dysplasia.

The aim of this first-in-man study is to evaluate the safety of calcium electroporation used in patients with Barrett's esophagus high-grade dysplasia through an endoscopic system.

This is a phase 2, open-label, umbrella study, with the purpose to evaluate the therapeutic efficacy and safety of chemoradiotherapy in combination with immunotherapy and/or targeted treatment in high-risk locoregionally advanced nasopharyngeal carcinoma. The specific grouping of patients' depends on the SYSUCC immune subtyping based on 100+ gene panel testing. The molecular subgroups include the Active, Evaded and non-Immune Subtypes. New treatment arms may be added and/or existing treatment arms may be closed during the study course on the basis of ongoing efficacy and safety as well as the current treatments available.

This is a phase 2, open-label, umbrella study, with the purpose to evaluate the therapeutic efficacy and safety of chemoradiotherapy in combination with immunotherapy and/or targeted treatment in high-risk locoregionally advanced nasopharyngeal carcinoma. The specific grouping of patients' depends on the SYSUCC immune subtyping based on 100+ gene panel testing.

This prospective study will take place at Hotel Dieu de France hospital in Lebanon. One hundred children aged 16 and under, undergoing cardiac surgery with cardiopulmonary bypass (CPB) for congenital heart diseases will be included between May 2020 and May 2021. The surgeries to be included will be the tetralogy of Fallot, transposition of the great arteries, ventricular septal defect, atrial septal defect and the atrioventricular canal defect. Any premature under 35 weeks of gestation, the presence of a genetic disease, an abnormal renal ultrasound, a preoperative renal failure with creatinine abnormal for age, or repeated urinary tract infections will be excluded from the study. After obtaining the informed consent of the parents, demographic information (age, weight, height, sex) will be collected..~Serum creatinine, lactic acid, urinary NGAL marker, and O2 saturation will be measured before the operation.~A pediatric NIRS sensor will be placed on the right side below the costo-vertebral angle covering the right kidney and continuous rSO2 will be recorded every 5 to 10 minutes throughout the operation as well as with each change of situation, then every hour in pediatric resuscitation until 24 hours postoperatively. The children will be divided into 2 groups of 50 patients each; Grp 1: No clinical intervention will be performed based on the NIRS and Grp 2: several maneuvers will be performed in case the NIRS values are below 50%, such as an increase in cardiac output, temperature, hemoglobin to optimize the NIRS value by up to 80%.~Surgical information (cardiac pathology, surgical procedure, operating time, duration of CPB, duration of aortic cross-clamping, duration of circulatory arrest, intraoperative complications) will be collected.~All patients will receive standard standard care during the study period. Patients will receive continuous infusion of furosemide (0.5-1 mg / kg / 6 hours) within the first 24-48 hours postoperatively.~Postoperatively, the need for catecholamines, the hemodynamic stability according to the Vasoactive-Inotropic Score (VIS), the delay to extubation, the stay in intensive care, the complications that occurred and the need for recourse to the dialysis will be noted.~Creatinine and lactic acid will be measured immediately postoperatively and then once a day until D2 and D7.~The urinary NGAL marker will be dosed immediately postoperatively and then at 2h, 6h, 12h and 24h with hourly monitoring of diuresis and NIRS until 24h postoperatively.

This prospective study will take place at Hotel Dieu de France hospital in Lebanon. One hundred children undergoing cardiac surgery for congenital heart disease between May 2020 and May 2021 will be included. After obtaining the informed consent of the parents, demographic and surgical information will be collected. Serum creatinine, lactic acid, urinary neutrophil gelatinase-associated lipocalin marker (NGAL), and oxygen (O2) saturation will be measured before the operation.~A pediatric NIRS sensor will be placed on the right side below the costo-vertebral angle overlying the right kidney and continuous regional oxygen saturation (rSO2) will be recorded every 5 to 10 minutes throughout the operation until 24 hours after surgery. The children will be divided into 2 groups; 50 each. Grp 1: No clinical intervention was performed based on NIRS values. Grp 2: several maneuvers are performed such as an increase in cardiac output, temperature, hemoglobin to optimize the value of NIRS > 80%. All patients will receive standard standard care during the study period and continuous infusion of furosemide (0.5-1 mg / kg / 6 hours) within the first 24-48 hours postoperatively will be administered to all patients. Creatinine and lactic acid will be measured immediately postoperatively and then once a day until D2 and D7.~The urinary NGAL marker will be dosed immediately postoperatively and then at 2h, 6h, 12h and 24h with hourly monitoring of diuresis and NIRS until 24h postoperatively.

Coronaviruses are a family of viruses with marked tropism for the respiratory system, being able to cause heterogeneous pathological states in humans ranging from the common cold to more serious diseases such as Respiratory Syndrome severe acute respiratory syndrome (SARS). In December 2019 in Wuhan in China, the first case of human infection by a new coronavirus was identified, currently called SARS-COV-2 (Severe Acute Respiratory Syndrome - Coronavirus - 2), characterized by high contagiousness and the possibility of causing a severe acute respiratory distress syndrome from which its acronym derives and which caused the state of a global pandemic in a few months. The disease caused by the SARS-COV-2 virus is called COVID 19.~The most frequent clinical manifestation of COVID-19 is pneumonia, which in about 20% of cases results in acute respiratory failure requiring oxygen therapy or ventilatory support. sometimes resulting in a picture similar to that caused by acute respiratory distress syndrome (ARDS), found in 60-70% of patients admitted to intensive care. The pathogenesis of classical ARDS involves three phases of the disease: an exudative, a proliferative and a fibrotic phase, which occurs when the removal of alveolar collagen fails and leads to progressive pulmonary fibrosis. It is not known whether the long-term evolution of the COVID 19 disease could result in the establishment of a fibrotic phase similar to that predicted by the pathogenesis of classical ARDS, which would lead to a chronic ventilatory deficit similar to that of pulmonary interstitial diseases, with serious impact on quality of life and mortality.~However, it is not well-known whether SARS-COV-2 pneumonia causes restitutio ad integrum or whether it can induce persistent parenchymal alterations and lung function abnormalities.~Very few studies have so far addressed the problem of clinical and functional recovery in these patients, most of them just before or after discharge and none specifically focused on patients admitted for ARF. Indeed most of these investigations were limited to a specific field such as symptoms, pulmonary function and radiological changes.There are no guidelines for the follow-up of COVID-19 patients, despite the British Thoracic Society (BTS) has published a guidance for scheduling post-hospitalization assessments.~Aim of this study, spontaneous,observational, both prospectic and retrospective, is to describe the long term (6 to 12 months) evolution of lung involvement in patients discharged after an episode of ARF due to COVID-19, identifying possible factor associated to lasting clinical, functional or radiological abnormalities.~Investigators will collect clinical, functional and radiological parameters during:~the hospital stay due to COVID-19 (H);~the 1-month after hospital discharge followup visit (V1);~the 3-months after hospital discharge followup visit (V2);~the 6-to-12-months after hospital discharge followup visit, performed for study subjects that at V2 show clinical and/or functional and/or radiological abnormalities due to sequelae of COVID-19 (V3).~For data analysis, all variables will be analyzed using descriptive method. Continuous variables will be presented as means, standard deviation, median and respective minimum and maximum values; the discrete or nominal variables will be expressed as frequencies and relative percentages. Subgroup analysis will be performed using X- 2 test or Fischer test when appropriate; parametric variables not normally distributed will be analyzed by Kruskal-wallis non-parametric test. Association between two or more parameters will be calculate with Spearman Correlation. p <0.05 values will be considered statistically significant.~This study was approved by the Local Ethic Committee.

In December 2019 the first case of human infection by a new coronavirus was identified, currently called SARS-COV-2 (Severe Acute Respiratory Syndrome - Coronavirus - 2), characterized by high contagiousness and the possibility of causing a severe acute respiratory distress syndrome from which its acronym derives and which caused the state of a global pandemic in a few months. The most frequent clinical manifestation of COVID-19 is pneumonia, which in about 20% of cases results in acute respiratory failure. Very few studies have so far addressed the problem of clinical and functional recovery in these patients, most of them just before or after discharge and none specifically focused on patients admitted for ARF. Indeed most of these investigations were limited to a specific field such as symptoms, pulmonary function and radiological changes. There are no guidelines for the follow-up of COVID-19 patients, despite the British Thoracic Society (BTS) has published a guidance for scheduling post-hospitalization assessments.~Aim of this study is to describe the long term (6 to 12 months) evolution of lung involvement in patients discharged after an episode of ARF due to COVID-19, identifying possible factor associated to lasting clinical, functional or radiological abnormalities collecting data from hospital stay, 1-month after hospital discharge, 3-months after hospital discharge and 6-to-12-months after hospital discharge.