Kornimate/medical-research-clean huggingface dataset:
sacubitril-valsartan in heart failure with preserved ejection fraction and secondary mitral valve regurgitation

Conditions: Heart Failure with Preserved Ejection Fraction; Functional Mitral Regurgitation

Summary: the main objective of this study is to assess the hemodynamic effects of sacubitril-valsartan in patients with heart failure with preserved ejection fraction and at least moderate atrial functional mitral regurgitation (afmr), using a combination of cardiopulmonary exercise testing and stress echocardiography (referred to as cpetecho) at baseline and after six months of therapy. the patients included in this study will be randomly assigned to receive sacubitril-valsartan as an adjunct to standard medical care, as opposed to adhering solely to the standard of care which involves sodium-glucose cotransporter-2 (sglt-2) inhibitor and mineralocorticoid receptor antagonist (mra).


Eligibility criteria:
inclusion criteria: * age \> 18 years. * new york heart association class ii to iv. * written informed consent. * left ventricular (lv) ejection fraction ≥ 50%. * objective evidence of cardiac structural and/or functional abnormalities consistent with the presence of lv diastolic dysfunction/raised lv filling pressures, including raised natriuretic peptides. * ≥ moderate functional mr assessed by transthoracic echocardiography within the previous year. exclusion criteria: * systolic blood pressure \< 100 mmhg. * potassium ≥ 5.2 mmol/l. * estimated glomerular filtration rate ≤ 25 ml/min/1.73m². * history of angioedema or unacceptable side effects during receipt of angiotensin converting enzyme (ace) inhibitors or angiotensin receptor blockers (arb). * structural mitral valve disease and previous or planned mitral valve intervention. * already receiving angiotensin receptor neprilysin inhibitor (arni, sacubitril-valsartan) therapy. * severe comorbid condition limiting life expectancy \< 24 months or inability to perform a maximal cpetecho. * myocardial infarction, unstable angina, coronary revascularization within 12 weeks prior enrolment. * severe aortic, tricuspid or pulmonary valve disease. * pregnancy, lactation, or use of any method of contraception that is not highly effective.
near-infrared autofluorescence (niraf)-guided total thyroidectomy: impact in low-volume, non-parathyroid institutions

Conditions: Autofluorescence; Thyroidectomy; Hypoparathyroidism; Hypocalcemia

Summary: hypoparathyroidism is the most frequent complication in total thyroidectomy. the use of near-infrared autofluorescence (niraf) intraoperatively, seems to reduce the rate of transient hypoparathyroidism. unfortunately, no effect on permanent hypoparathyroidism has been shown. in order to cover every aspect of the impact of niraf in thyroid surgery, an evaluation in low-volume, non-parathyroid institutions is needed. this is the overall aim of our current studies. the objective of this specific study is to evaluate the impact of niraf on immediate, transient and permanent hypoparathyroidism following total thyroidectomy in low-volume, non-parathyroid institutions.

patients referred for total thyroidectomy will undergo niraf-assisted surgery (fluobeam lx) at two low-volume ent-departments with no experience in parathyroid surgery. pth and ionized calcium will be assessed preoperatively, on postoperative day 1 (pod1) and minimum two months following surgery. patients who still fulfill the criteria for hypoparathyroidism at that point will be followed until one year following surgery. the rates of immediate, transient and permanent hypoparathyroidism will be assessed and compared to a historic cohort.

Eligibility criteria:
inclusion criteria: * patients referred for total thyroidectomy * age \> 18 * able to understand patient information * able to give informed consent exclusion criteria: * previous thyroid surgery * need for accelerated surgery * insufficient biochemical profile
a phase i/ii study to evaluate azd5851 in gpc3+ advanced/recurrent hepatocellular carcinoma

Conditions: Hepatocellular Carcinoma

Summary: a phase i/ii study to evaluate azd5851 in patients with gpc3+ advanced/recurrent hepatocellular carcinoma.

this first-time in human, single-arm, open-label multicentre phase i/ii study will evaluate the safety, tolerability, antitumour activity, cellular kinetics, pharmacodynamics, and immunogenicity of azd5851 in adult participants with gpc3+ advanced/recurrent hcc, where at least one line of prior therapy has failed/or was intolerable, or participant/investigator decision.

Eligibility criteria:
inclusion criteria: 1. participant must be 18 years or older and has voluntarily agreed to participate by giving written informed consent. 2. participants with confirmed advanced/recurrent or metastatic and/or unresectable hcc based on histopathological findings 3. completed or were unable to tolerate at least one prior line of standard systemic therapy for hcc and/or participant/investigator decision. 4. gpc3-positive tumour as determined by a central laboratory using an analytically validated ihc assay 5. barcelona clinic liver cancer stage b (if not amenable to local treatment/surgery) or c prior to apheresis 6. child-pugh score: grade a 7. participants with hbv and hcv undergoing management of these infections per institutional practice. exclusion criteria: 1. active or prior documented gastrointestinal (gi) variceal bleed or history of upper gi bleeding, ulcers, or esophageal varices with bleeding within 12 months 2. history of liver transplantation or on waiting list 3. current clinically significant ascites 4. main portal vein thrombus, or tumor thrombus invasion of mesenteric vein / inferior vena cava 5. uncontrolled intercurrent illness 6. active infections 7. positive serology for hiv 8. history of hepatic encephalopathy within 12 months prior to treatment allocation 9. history of chronic or recurrent (within the last year) severe autoimmune or immune mediated disease requiring steroids or other immune-suppressive treatments. 10. prior treatment with any car-t therapy directed at any target or any therapy that is targeted to gpc3. 11. receipt of the last dose of anticancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumour embolisation, or monoclonal antibodies, investigational product) within 5 half-lives or ≤ 21 days (whichever is shortest).

Keywords: hepatocellular carcinoma liver cancer liver neoplasm advanced hcc hcc metastatic liver cancer car-t cart azd5851 t-cell cell therapy
clinical trial of humax-cd4, a new drug to treat advanced stage t-cell lymphoma in the skin.

Conditions: Cutaneous T-Cell Lymphoma

Summary: the purpose of this trial is to determine the effect of humax-cd4, as a treatment for advanced stage (late stage) cutaneous t-cell lymphoma (ctcl). almost all participants who are affected by late stage ctcl have many cancerous cells which bear a receptor called cd4. humax-cd4 is an investigational drug directed against this receptor. there is no placebo in this trial; all participants will be treated with humax-cd4. the response rates, duration of responses, relief of symptoms, and safety profile of humax-cd4 will be evaluated during this trial.


Eligibility criteria:
inclusion criteria * medical diagnosis of ctcl, and positivity for the cd4 receptor. * late stage ctcl. * have received at least one prior anti-cancer therapy with inadequate effect. * world health organization (who) performance status 0,1 or 2 exclusion criteria * certain rare types of ctcl. * previous treatment with other anti-cd4 medications. * more than two previous treatments with systemic chemotherapy. * certain anti-psoriasis or anti-cancer therapies within the last 4 weeks before entering this trial. * some types of steroid treatments less than two weeks before entering the trial. * prolonged exposure to sunlight or uv light during the trial. * other cancer diseases, except certain skin cancers or cervix cancer. * chronic infectious disease requiring medication. * certain serious medical conditions, including kidney or liver disease, some psychiatric illnesses, and stomach, lung, heart, hormonal, nerve or blood diseases. * pregnant or breast-feeding women. * women of childbearing age who are unable or unwilling to use an iud or hormonal birth control during the whole trial. * if you are participating in another trial with a different new drug 4 weeks before you enter this trial. note: other protocol defined inclusion and exclusion criteria may apply.

Keywords: skin cancer lymphoma mycosis fungoides sezary syndrome
psyllium in pediatric ibs

Conditions: Irritable Bowel Syndrome

Summary: the goal of this clinical trial is to learn if a fiber (psyllium) can change the way bacteria use fructans (a type of sugar) and whether psyllium can help decrease childhood irritable bowel syndrome (ibs) symptoms when eating fructans. the main questions it aims to answer are: aim 1: the effect of psyllium at two doses given with a fructan meal on microbial fructan fermentation (intracolonic ph; h2 gas production; gut microbiome composition; fecal short-chain fatty acids, lactate, glycomics). aim 2: determine the impact of psyllium given with a fructan meal on fructan-induced gi symptoms. participants will first be asked to eat a specific diet over two three-day periods to determine if fructans worsen their ibs symptoms. those with worsening symptoms with fructans will be asked to participate in the second part of the study. this includes two weeks of baseline (no change in diet) and two weeks of eating a specific diet with fructans with either psyllium or glucose. participants will be asked to complete pain and stool diaries, submit stool specimens, swallow a pill to capture gut acid levels, and give breath samples.


Eligibility criteria:
inclusion criteria: * children between the ages of 12-17 years meeting pediatric rome iv criteria for ibs exclusion criteria: * children who have had previous bowel surgery, have documented gi disorders (e.g., ulcerative colitis), or a serious chronic medical condition (e.g., diabetes) * weight and/or height are \&gt; or \&lt; 2 sd for age * have chronic conditions with gi symptoms (e.g., cystic fibrosis) * have been on antibiotics or probiotics within 3 months (because of potential alterations to the gi microbiome0 * girls who are pregnant (tested with urine beta-human chorionic gonadotropin at the initial visit)

Keywords: abdominal pain
a 20-week study assessing the efficacy of apremilast in patients with eb simplex generalized

Conditions: Epidermolysis Bullosa Simplex; Genodermatosis

Summary: the goal of this clinical trial is to assessing the efficacy and safety of apremilast in patients \> 6 years of age with eb simplex generalized . the main question it aims to answer are: describe efficacity of this treatment. participants will take treatments and have to use bullets during the study period.

the patient will have 7 visits. after confirmation of inclusion criteria and no exclusion criteria, the study will be explain to the patient after signing the inform consent and be included in the study treatment period (period 1); challenge period this period will be the first treatment period that will occur from 8 weeks. during this period the patient will see the doctor at the hospital, he will perform the study procedures the second period : dechallenge (period 2): all patients stop their treatment for 4 weeks. the second treatment period - rechallenge (period 3) the patient will take the treatment for a second 8 weeks period at week 20 - end of study at each visit: the investigator at each visit compliance to the treatment and adverse events, measure vital signs and perform clinical examination. the patient will assess the different questionnaires, for the study

Eligibility criteria:
inclusion criteria: * male or female patients 6 years or older * laboratory confirmed diagnosis of ebs-sev due to krt5 or 14 mutation (autosomal) * mean daily number of new blisters \>3. * subject/caregiver agrees not to use any topical therapies other than the investigator approved exclusion criteria: * - ebs lesions requiring oral therapy to treat an infection * use of any diacerein containing product within 6 months prior to visit 1 * use of systemic immunotherapy or cytotoxic chemotherapy within 60 days prior to visit 1 * use of systemic steroidal therapy within 30 days prior to visit 1 * use of any systemic product that, in the opinion of the investigator, might put the subject at undue risk by study participation or interferes with the study assessments within 30 days prior to visit 1

Keywords: apremilast children pediatric
management of sepsis in resource limited settings using a delphi method.

Conditions: Sepsis

Summary: rapid evolution of sepsis syndromes means that timely diagnosis and treatment are critical in improving outcomes but this may be difficult to achieve in many low- and middle- income countries (lmics) and there is a lack of high quality clinical evidence to guide diagnosis and management in lmic settings. the wide variability in health systems in lmics means that additional areas of guidance may be required where staff or facilities are lacking. in the absence of clinical data, to address some of these issues, the investigators aim to use delphi methodology to obtain experts consensus statements on some specific aspects of sepsis management in lmics.

the investigators aim to use a delphi process to generate expert consensus practice statements in the context of diagnosis and management of sepsis in lmics, including identification of aspects of sepsis diagnosis and management in lmics not covered by existing guidelines. the questions will undergo several iterative rounds and will be in multiple-choice or likert scale format. a study steering group will review the results of each round via video conference and design the questionnaire for the next survey. summary results of each round will be presented to experts, along with the survey questionnaire for the next round. the survey process will be repeated with the modified questionnaire. the delphi rounds will continue until the desired consensus and stability are achieved.

Eligibility criteria:
inclusion criteria: * recognized experts meeting pre-defined criteria (below) from a wide geographical distribution with approximately 70% from lmics. 1. clinical expertise in adult sepsis management, and 2. demonstrated involvement with sepsis related research, educations, policy/protocols, professional activities exclusion criteria:

Keywords: sepsis septic shock low- and middle- income countries lmic delphi resource-limited setting
local anesthetic for total mastectomy surgery

Conditions: Breast Pain

Summary: pain following mastectomy surgery for breast cancer can be significant. poorly managed pain in the immediate time-period following surgery can potentially lead to long-term (chronic) pain conditions. there is still a need to find the safest, least invasive, and most effective method to manage this pain. the investigators believe that a new technique of injecting local anesthesia (freezing) in to specific areas at the end of mastectomy surgery may be a very important step to managing pain after breast surgery. the investigators would like to begin by performing a pilot study, meaning the investigators will perform the technique in patients and compare what their pain outcomes are to patients who have not had the technique.

mastectomy is associated with significant acute postoperative pain. it has been shown that inadequately managed post-mastectomy pain in breast cancer patients can have detrimental physiological, psycho-behavioural, recovery and healthcare utilization consequences. most significantly, acute postoperative pain appears to be a substantial risk factor for progression to chronic post-surgical pain (cpsp), occurring in up to 68% of patients,, with higher severity of acute pain being linked with a greater progression to cpsp. a multimodal analgesic approach is the optimal method of reducing the risk of progression to cpsp, and there are a number of analgesic techniques that can be used to reduce the incidence of acute postoperative pain. of the analgesic techniques used, the most common are multimodal systemic analgesia, thoracic paravertebral blockade, thoracic epidural analgesia, local anesthetic wound infiltration, and more recently pecs blocks and serratus plane blocks. the former three techniques are all associated with drawbacks including technical challenges, high risk of adverse effects, and limited evidence to minimize the progression to cpsp states, whilst local anesthetic wound infiltration has highly variable pain outcomes. therefore, an alternative, safer, and more effective technique would be ideal. local infiltration analgesia (lia) techniques have been demonstrated to be efficacious in joint surgery, whilst injection of local anesthesia in the serratus plane to target some of the intercostal and pectoral nerves may have some benefit in mastectomy surgery. however, nobody has yet performed lia around these nerves in breast surgery, and the investigators feel that this has enormous potential.

Eligibility criteria:
inclusion criteria: * undergoing elective or urgent, primary, unilateral mastectomy with or without axillary lymph node dissection * asa-ps i-iii * 18-85 years of age, inclusive * 50-100 kg, inclusive * bmi 18 - 40 exclusion criteria: * bilateral mastectomy surgery * revision mastectomy surgery * inability or refusal to provide informed consent * chronic pain state * neuropathic pain * opioid dependence * allergy to local anesthesia * allergy to opioids
stereotactic radiotherapy for oligoprogressive er+/her- metastatic breast cancer, a prospective phase 2 study (oligopro-breast)

Conditions: OligoProgressive Metastatic Disease

Summary: the oligopro-breast trial is a phase ii study targeting women with er+/her2- metastatic breast cancer who have been on endocrine therapy and/or cdk4/6 inhibitors for at least 6 months, and show progressive disease at 1-3 extracranial metastases, which are treatable locally. the trial aims to investigate if treating these resistant metastases with sbrt (or other local treatments if sbrt is not possible) can extend the use of the current systemic therapy. patients will continue their existing systemic treatment while receiving sbrt on all progressive lesions. if new oligoprogression occurs, sbrt will be performed again. a new systemic treatment line will start if there is polyprogression (more than 3 lesions at once), progression of more than 6 lesions over 12 months, intracranial progression, or lesions that cannot be treated locally. the scientific question is whether local treatment of resistant metastases can prolong the effectiveness of ongoing systemic therapy, which is particularly beneficial if the treatment is well-tolerated. the primary objective is to measure the proportion of patients surviving without changing their systemic treatment line at 6 months after sbrt. this trial is significant for patients as it explores a method to potentially extend the duration of effective and well-tolerated treatments, offering hope for better management of metastatic breast cancer.


Eligibility criteria:
inclusion criteria: * ecog performance status 0-2. * histologically confirmed er+/her2- mbc. * history of polymetastatic disease. patients with genuine oligometastatic disease and 1-3 oligoprogressive lesions are only allowed if ablative therapy of all metastases is deemed impossible. * under 1st to 2nd systemic treatment line with hormonotherapy and/or cdk4/6 inhibitors for at least 6 months before progression. * progressive disease at 1-3 extracranial sites. * ability to treat all progressive lesions locally according to the treating radiation oncologist. exclusion criteria: * second malignancy if it is not in complete remission. * previous local treatment for oligoprogression under the current systemic treatment line * current progression in a lesion that has been treated with sbrt before and is not amendable for surgery or radiofrequency ablation (rfa). * progressive or newly diagnosed brain metastases. known brain metastases that have been nonprogressive for at least 6 months, are not an exclusion criterion. * inability to continue the same st line after local therapy (for example because of toxicity or patient refusal). * pregnancy. * inability to sign the informed consent.

Keywords: oligoprogression metastatic breast cancer cdk4/6 inhibitors sbrt sabr radiotherapy
effects of seaweed extract on postprandial response to white bread

Conditions: Glycemic Control; Diabetes Mellitus Risk; Glucose Intolerance; Postprandial Hyperglycemia; Healthy Subjects

Summary: the study is designed to determine whether seaweed extract added to a carbohydrate-rich meal, can lower blood glucose levels after its consumption, and hence lower its glycaemic index, and if this effect is mediated through effects on insulin. it is designed as an acute, randomised, cross-over, controlled, three-arm dietary intervention trial in healthy subjects. participants will be asked to consume either white bread, white bread with lower dose of seaweed extract or white bread with higher dose of seaweed extract.the effects on plasma glucose levels and levels of insulin will be determined over 3 hours after the consumption.

it has been shown in a large number of in vitro studies that seaweed extracts act as potent inhibitors of enzymes of carbohydrate digestion suggesting their potential to modulate postprandial glycaemic response and prevent the damaging effects of hyperglycaemic state. however, the results from human trials are limited and inconsistent. the investigators confirmed that the in vitro inhibitory effects of seaweed extracts depend on the type, level and ratio of bioactive compounds, and optimised the composition of the extract to obtain the most potent one, to be tested in the proposed study. the present study will determine whether the seaweed extract added to a carbohydrate-rich meal, can lower blood glucose levels after its consumption, and hence lower its glycaemic index, and if this effect is mediated through effects on insulin or determined by the individual levels of digestive enzymes. healthy volunteers will be asked to consume three different meals: (1) white bread; (2) white bread with the lower dose (ld) of the extract; (3) white bread with the higher dose (hd) of the extract the levels of glucose and insulin will be measured in plasma isolated from blood samples obtained before and up to 3 hours after the consumption of each meal. additional measurements taken at the screening will include blood pressure values and blood lipids levels. all participants will be characterized for the activity of salivary a-amylase.

Eligibility criteria:
inclusion criteria: * 18-65 years old * healthy exclusion criteria: * smoking * diagnosis of any chronic illness (including diabetes, hypertension, gastrointestinal diseases etc.) * on long term prescribed medication (except contraceptives) * pregnant or lactating * on a special diet or dietary regimen (for weight management or if regularly consuming fruit extract supplements) * allergy to fruits vegetables or pollen * unwillingness to follow dietary recommendations or record the diet during recommended period * donated blood 4 weeks before or intend to donate blood during the study or 4 weeks after the last study samples * participation in another research project in parallel which also involves dietary intervention (e.g. taking vitamin supplements) or requires sampling of blood

Keywords: seaweed ascophyllum blood glucose insulin postprandial hyperglycemia