cyrilzakka/clinical-trials huggingface dataset:
Intracerebral Gene Therapy for Children with Early Onset Forms of Metachromatic Leukodystrophy

The objective of this open-label, single arm, monocentric, phase I/II clinical study is to assess safety and efficacy of ARSA gene transfer in the brain of children affected with early onset forms of Metachromatic Leukodystrophy (MLD). For this purpose, an adeno-associated virus serotype rh.10 (AAVrh.10) vector will be used to transfer the ARSA cDNA coding for Arylsulfatase A (ARSA) enzyme into the brain of children. Five patients with early onset form of MLD, age ranging from 6 months to 4 years, will be included in this protocol and will be followed during 24 months.

Patients will be selected at presymptomatic or early stage of their disease, following clinical, neuropsychological and brain imaging criteria.

Twelve simultaneous injections of the investigational medicinal product will be performed in the white matter of both brain hemispheres, through 6 image-guided tracks, with 2 deposits per track.

A low dose (1x10EXP12 vg total) will be administered to the first 2 patients, while the last 3 will receive a higher dose (4x10EXP12 vg total).

Safety and efficiency will be evaluated based on clinical, neuropsychological, radiological, electrophysiological and biological parameters.


Eligibility Criteria:
Inclusion Criteria:

* Boys or girls with an early onset form of MLD.
* Age between 6 months and 5 years, inclusive
* Diagnostic of MLD based on the measurement of ARSA activity in leukocytes and the accumulation of sulfatides in urine, along with normal activity of at least one other sulfatase
* Informed consent signed up and willingness for monitoring 2 years after treatment.
* Normal values for standard laboratory tests

Exclusion Criteria:

* Absence of ARSA protein by immunocytochemistry and/or ELISA
* Gestational age \<32 weeks of amenorrhoea and age \< 1 year
* Brain atrophy with a subdural space \> 10 mm in the frontal region
* Performance IQ\<50 at WPPSI-III or cognitive function \< 3rd percentile at the Bayley's test of infant development
* If age \> 16 months at inclusion, inability to walk few steps alone OR inability to walk few steps with support on one side along with inability to stand up alone
* Impossibility for anesthesia
* Malignancy, cardiac malformation, liver dysfunction, or renal dysfunction
* Neurological disorder, except benign, not related to MLD.
* Any other clinically significant untreated co-morbid medical condition as determined by the clinical investigator, including cardiac, pulmonary or kidney disease.
* MRI impossibility
* Evoked potential impossibility
* Participation to another therapeutic clinical trial for MLD.
* Unaffiliated to any French or any other National Health Insurance.
Protocol-based Management and Perioperative Outcomes in Patients With Chronic Antithrombotic Therapy

The purpose of this pragmatic interventional study is to evaluate whether a protocol-based management of antithrombotic drugs can reduce a composite of perioperative outcomes in patients with chronic antithrombotic therapy before surgery.

Aging population and chronic medical disease make the management of surgical patients more complex. About one tenth of patients scheduled for surgery are taking antithrombotic medications. Coagulation disturbance induced by these medications may increase the risk of bleeding, whereas withholding these medications may increase the risk of thrombotic events. It is a dilemma when managing these patients.

The guidelines and expert consensus published by multiple disciplinary teams constitute the perioperative antithrombotic management protocols. However, the effects of perioperative antithrombotic management guided by these guidelines or expert consensus are seldom reported. The investigators hypothesize that a protocol-based perioperative antithrombotic management can benefit patients with chronic antithrombotic therapy before surgery.

Eligibility Criteria:
Inclusion Criteria:

* 1. Patients with continuing antithrombotic therapy (including antiplatelet and/or anticoagulant therapies) for cardiovascular and cerebrovascular diseases for more than 2 weeks.
* 2. Patients who have one or more of the following situations: (1) non-valvular atrial fibrillation with a CHA2DS2-VASc score \>4; (2) post-artificial valve replacement (including mitral valve, ball-cage valve or tilting disc aortic valve); (3) venous thromboembolism occurred within 1 year, or venous thromboembolism with other high-risk factors which require long-term anticoagulation treatment; (4) coronary heart disease with coronary stent implantation, thrombolytic therapy or other coronary procedures within 2 years, or who had undergone coronary artery bypass grafting within 1 year, or who experienced myocardial infarction or acute coronary syndrome within 1 year; (5) a history of stroke/transient ischemic accident within 1 year, or a history of cervical or intracranial revascularization treatment within 1 year; (6) peripheral arterial disease.
* 3. Patients who are scheduled to undergo intra-abdominal surgery (including general and urologic surgery).
* 4. Patients who sign written informed consents.

Exclusion Criteria:

* 1. Refuse to participate.
* 2. Emergency surgery.
* 3. Unable to complete the preoperative assessment and follow-up plan.
* 4. Other reasons that are considered unsuitable for study participation by the investigators or the attending doctors.
Evaluation of a Dry Powder Aerosol Dispersion Mechanism by Radiolabeling Techniques

The primary objective is to admix a radiolabel with albuterol sulphate for incorporation into the Handihaler® device for inhalation studies. This will allow for the investigators to determine the regional lung deposition of drug inhaled from the standard Handihaler® device compared to a novel modification of the device to provide more effective dispersion and aerosolization of the coated albuterol powder. The new mechanism of action for proof-of-concept testing consists of a bead (5.1 mm; expanded polystyrene foam) coated with drug powder, as opposed to the standard lactose formulation-filled capsule.


Eligibility Criteria:
Inclusion Criteria:

* healthy volunteers adults

Exclusion Criteria:

* chronic illness
Furosemide Stress Test Guiding Initiation of Renal Replacement Therapy

Does Early Initiation of Renal Replacement Therapy Have an Impact on 7-day Fluid Balance in Critically Ill Patients with Acute Kidney Injury with Positive Furosemide Stress Test?: a Multicenter Randomized Controlled Trial

The objective is to determine if early initiation of renal replacement therapy guided by positive furosemide stress test has an impact on 7-day fluid balance in critically ill patients with acute kidney injury

Eligibility Criteria:
Inclusion Criteria:

* Age older than 18 years old and admission in an ICU
* Acute kidney injury (defined by serum creatinine increase ≥ 0.3 mg/dL or urine output ≤ 0.5 mL/kg/hour according to KDIGO criteria)
* Informed consent provided by the patient or person with decisional responsibility
* Indwelling bladder catheter
* Documented cause of acute kidney injury from acute tubular necrosis e.g. presence of granular or epithelial casts on urine sediment, FeNa more than 1%, Feurea more than 50%, urine or plasma neutrophil gelatinase-associated lipocalin (NGAL) more than 150 mg/dL
* Opinion of the treating clinical team that patient was well resuscitated and sufficiently clinically stable for the intervention or by noninvasive or invasive measurements i.e. fluid accumulation at least 5% plus at least one of the following e.g. chest radiography, central venous pressure ≥ 8 mmHg, pulse pressure variation \< 13%, inferior vena cava collapsibility index \< 50% in spontaneously breathing patients or distensibility index \< 18% in mechanically ventilated patients

Exclusion Criteria:

* Baseline serum creatinine ≥ 2 mg/dL (male) and ≥ 1.5 mg/dL (female) within 3 months
* Evidence of volume depletion at the time of furosemide administration or active bleeding
* Evidence of obstructive uropathy, renal vein thrombosis or renal artery stenosis, thrombotic microangiopathy, glomerulonephritis, tumor lysis syndrome
* History of renal allograft
* Known pregnancy
* Allergy or known sensitivity to loop diuretics
* Need for emergency renal replacement therapy at randomization or evaluation by the clinical team that the renal replacement therapy should be deferred
* Patient is moribund with expected death within 24 hr or whom survival to 28 days is unlikely due to an uncontrollable comorbidity (cardiac, pulmonary or hepatic end-stage disease; hepatorenal syndrome; poorly controlled cancer; severe post-anoxic encephalopathy; etc.)
* Patients with advance directives issued expressing the desire not to be resuscitated
* Prior treatment with RRT within 30 days
Silver Nanoparticles in Multidrug Resistant Bacteria

Recently, silver nanoparticles (AgNPs) have been widely used in various applications as antimicrobial agents, anticancer, diagnostics, biomarkers, cell labels, and drug delivery systems for the treatment of various diseases. The present study investigated the bactericidal effect of AgNPs against Methecillin Resistant Staph. aureus (MRSA) and Vancomycin resistant Staph aureus (VRSA)


Eligibility Criteria:
Inclusion Criteria:

* Intensive care patients

Exclusion Criteria:

* none
The Pittsburgh Study Early Childhood

The Early Childhood Collaborative of The Pittsburgh Study is a community-partnered, county-wide implementation of programs for children and families from birth through formal school entry to address real-world challenges that exist in providing effective preventive interventions for families with young children, particularly low-income families.

The Early Childhood Collaborative of The Pittsburgh Study is a community-partnered, county-wide implementation of programs for children and families from birth through formal school entry to address real-world challenges that exist in providing effective preventive interventions for families with young children, particularly low-income families. Specifically, The Early Childhood Collaborative seeks to increase engagement (uptake and retention) in evidence-based interventions by (1) initially assessing families' resources and challenges, (2) offering families a menu of intervention options tailored to their resources/needs, and (3) providing these services at multiple locations to optimize accessibility. The Early Childhood Collaborative involves population-level utilization of multiple platforms that families, particularly families at greater risk for health disparities, typically use, including health care (birthing hospitals, pediatric care, federally qualified health centers), Women, Infants, and Children nutritional clinics, and family centers. The Early Childhood Collaborative will locate services in these platforms and at family's homes. The Early Childhood Collaborative focuses on child thriving and flourishing as key outcomes of interest, and community strengths as key drivers of change. To promote sustainability, investigators include representatives from the Departments of Human Services and Health who are responsible for funding and implementing home visiting programs in the greater Pittsburgh community, with the goal of generating infrastructures and capacity in existing community agencies for providing evidence-based behavioral health care.

Eligibility Criteria:
Inclusion Criteria:

* Allegheny County Residency, legal custodian of child

Exclusion Criteria:

* Non-English speaking
Outcome of Pancreatic Stump Closure Following Resection of Tumors of the Head of the Pancreas.

Chart review evaluating outcome of patients in whom following resection of a tumor involving the head of the pancreas no anastomosis of the pancreatic stump was done to the gastrointestinal tract.


Eligibility Criteria:
Inclusion Criteria:

* Pathologically proven carcinoma of the head of pancreas or other periampullary carcinoma treated by pancreaticoduodenectomy.

Exclusion Criteria:

* Patients undergoing pancreaticoduodenectomy for other indications (i.e. trauma)
* Charts not available for review.
Post-prostatectomy Radiation Therapy--Moderate Versus Ultra-hypofractionated (Also Known as Stereotactic Body Radiation Therapy [SBRT])

The primary purpose of this study is to compare the quality of life (QOL) reported by prostate cancer patients 2 years after treatment with ultra-hypofractionated post-prostatectomy radiation therapy (also known as stereotactic body radiation therapy \[SBRT\]) versus the self-reported QOL of those treated with moderately hypo-fractionated post-prostatectomy radiation (a current standard of care option).

Conventional or moderately hypo-fractionated radiation therapy are the current standard of care treatment options for men receiving post-prostatectomy radiation therapy. These treatment regimens typically span 4-8 weeks, representing a high burden of therapy, which may result in decreased utilization of salvage radiotherapy, the only potentially curable treatment for men with relapsed disease following prostatectomy. Ultra-hypofractionated radiation therapy (also known as stereotactic body radiation therapy \[SBRT\]) would decrease the total number of treatments to 5, delivered over 2 weeks, which would greatly reduce treatment burden.

Eligibility Criteria:
Inclusion Criteria:

* Men age ≥ 18 with histologically confirmed prostate cancer after radical prostatectomy with a PSA ≥ 0.1 ng/mL
* Interval between prostatectomy and planned radiation therapy start date ≥ 6 months
* KPS ≥ 70
* Patients with equivocal pelvic lymph nodes on imaging are eligible if the nodes are ≤ 1.5 cm in the short axis (equivocal evidence of metastatic disease outside of the pelvis on standard imaging requires documented negative biopsy)
* Ability to complete the EPIC-26 quality of life questionnaire
* Ability to obtain tissue from radical prostatectomy specimen for review by Michigan Medicine Pathology
* Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

* Prior history of pelvic radiation therapy
* History of moderate/severe or active Crohn's disease or ulcerative colitis
* History of bladder neck or urethral stricture
* Evidence of distant metastatic disease or nodal involvement beyond the common iliac vessels
* Initiation of androgen deprivation therapy with a LHRH / GnRH agonist or antagonist greater than 6 months prior to enrollment or receipt of any non-LHRH / GnRH agonist or antagonist androgen deprivation or anti-androgen therapy
* History of another invasive malignancy within the previous 3 years except for adequately treated squamous or basal cell skin cancer
* Any condition that in the opinion of the investigator would preclude participation in this study
Vitamin D Inadequacy is Associated With Incidence of Type 2 Diabetes

Emerging evidence suggests that vitamin D \[25-hydroxyvitamin D; 25(OH)D\] may play a role in the etiology of type 2 diabetes. Vitamin D levels are lower in those with type 2 diabetes and impaired glucose tolerance (IGT) compared with those with normal glucose tolerance (NGT). In addition, a few prospective studies have shown a significant inverse association of baseline serum 25(OH)D with incident diabetes. To date, however, the exact mechanisms through which vitamin D affects diabetes risk are not yet fully known, particularly whether vitamin D plays a role in insulin resistance (IR) and/or b-cell dysfunction, the main pathophysiological disorders underlying type 2 diabetes. So, the investigators plan to examine the prospective associations of baseline vitamin D \[25-hydroxyvitamin D; 25(OH)D\] with insulin resistance (IR), b-cell function, and glucose homeostasis in subjects at risk for type 2 diabetes.


Eligibility Criteria:
Inclusion Criteria:

* one or more risk factors for diabetes, including:

  * obesity
  * hypertension
  * dislipidemia
  * a family history of diabetes

Exclusion Criteria:

* previous diagnosed diabetes
* vitamin D supplement.
Study of REGN2810 in Patients With Advanced Cutaneous Squamous Cell Carcinoma

Groups 1 to 4 To estimate the clinical benefit of cemiplimab monotherapy for patients with: metastatic (nodal or distant) cutaneous squamous cell carcinoma (CSCC), or unresectable locally advanced CSCC

Group 6 To provide additional efficacy and safety data for cemiplimab monotherapy in patients with advanced CSCC (metastatic \[nodal or distant\] or locally advanced treated with cemiplimab


Eligibility Criteria:
Key Inclusion Criteria:

* At least 1 measurable lesion
* Eastern Cooperative Oncology Group (ECOG) performance status ≤1
* Adequate bone marrow function
* Adequate renal function
* Adequate hepatic function
* Archived or newly obtained tumor material
* Patients must consent to undergo biopsies of CSCC lesions (Groups 2, 4, and 6)
* Surgical or radiological treatment of lesions contraindicated

Key Exclusion Criteria:

* Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-related adverse events
* Prior treatment with an agent that blocks the PD-1/PD-L1pathway
* Prior treatment with a BRAF inhibitor
* Prior treatment with other immune-modulating agents within fewer than 4 weeks prior to the first dose of cemiplimab, or associated with immune-mediated adverse events that were ≥ grade 1 within 90 days prior to the first dose of cemiplimab, or associated with toxicity that resulted in discontinuation of the immune-modulating agent. Examples of immune-modulating agents include therapeutic vaccines, cytokine treatments, or agents that target cytotoxic T-lymphocyte antigen 4 (CTLA-4), 4-1BB (CD137), or OX-40.
* Untreated brain metastasis(es) that may be considered active
* Immunosuppressive corticosteroid doses (\>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of cemiplimab
* Infection with human immunodeficiency virus (HIV) and/or chronic/active infection with hepatitis B virus or hepatitis C virus
* History of non-infectious pneumonitis within the last 5 years
* Allergic reactions or acute hypersensitivity reaction attributed to antibody treatments
* Known allergy to doxycycline or tetracycline
* Patients with a history of solid organ transplant
* Any medical co-morbidity, physical examination finding, or metabolic dysfunction, or clinical laboratory abnormality that renders the patient unsuitable

Other protocol-defined inclusion/exclusion criteria apply
Maternal Exercise and Antenatal Anxiety

This is a randomized controlled trial study. We evaluate effectiveness of maternal exercise on anxiety during normal pregnancy compared to those who receive antenatal care regularly. We plan to recruit 220 healthy pregnant women over the age of 18 in Shenzhen and to use a standard maternal exercise from Korea as intervention.


Eligibility Criteria:
Inclusion Criteria:

* Pregnant women who are over 18 years old and confirmed to be pregnant in Shenzhen Dapeng New District.

Exclusion Criteria:

* 1.pregnant women who have accepted maternal exercise training (at least twice a week in last month);2.pregnant women who have orthopedics, cardiovascular or mental diseases; 3.pregnant women who have or had any condition as follows:miscarriage more than two times,premature delivery,placenta previa,fetal dysplasia, low weight before pregnancy (BMI \<17.5),polycyesis,preeclampsia,premature rupture of membranes,Uterine growth retardation,cervical/ligation,repeated vaginal bleeding,anemia or diabetes; 4.the gestational age is less than 12 weeks or more than 16 weeks;5.received psychotherapy or psychotropic medication within 6 months before the study;6.can not participate in regular inspections.
Comparison of Efficacy Between ILM Forceps

This study is a Single center, prospective, observational, multi surgeon randomized controlled trial. Subjects will be assessed pre-operatively, operatively and at 1 month postoperatively. Clinical evaluations will include measurement of visual acuity and optical coherence tomography (OCT).


Eligibility Criteria:
Inclusion Criteria:

• 19y and older patients with symptomatic ERM (grade 2-3) or Macular hole (non flap-requiring) for elective ILM peeling surgery.

Exclusion Criteria:

* Co-morbid diabetic retinopathy of any grade.
* Neovascular AMD.
* Previous vitrectomy.
* Previous retinal detachment treated with scleral buckle or pneumatic retinopexy.
* Uncontrolled glaucoma or previous glaucoma surgery.
* Combined phacovitrectomy.
* Macula holes with severity requiring flap.
Nonverbal Communication in Aged People

Musical interventions improve the emotional state of patients with Alzheimer's disease (AD) while having a positive impact on the caregiver's well-being. However, the factors that could be responsible for this positive effect remain unknown. Among these, the sensory-motor synchronization (SMS) of movements to the musical rhythm, frequently observed during musical activities and possible up to the advanced stages of AD, could modulate the emotional state. Several recent studies have shown that rhythmic training (or SMS) influences the organism at the motor, cognitive and social levels while activating the cerebral reward circuit. This action that generates pleasure also facilitates non-verbal emotional expression. However, the conditions that modulate SMS and their relationship to nonverbal communication, emotional, behavioral and cognitive state have not yet been studied in healthy or pathological elderly.


Eligibility Criteria:
Inclusion Criteria:

Cases : Patients with neurodegenerative disease (AD or related disease)

* Native French Language
* Corrected auditory and/or visual deficiency
* Right-handed
* Image rights consent signed by the patient Controls: People with no neuropathological disease
* Native French Language
* Corrected auditory and/or visual deficiency
* Right-handed
* Image rights consent signed by the control

Exclusion Criteria:

-