cyrilzakka/clinical-trials huggingface dataset:
Conversion of Tislelizumab Combined With Chemotherapy in Unresectable Esophageal Squamous Cell Carcinoma

Whether the introduction of immunotherapy can transform unresectable esophageal cancer into resectable, or even achieve R0 surgical resection, has not been reported yet. We plan to conduct a prospective, single-center, single-arm phase II clinical study of the safety and efficacy of tislelizumab combined with chemotherapy in the treatment of unresectable esophageal squamous cell carcinoma.

For patients not eligible for R0 resection (defined as locally advanced unresectable esophageal cancer), preoperative treatment can theoretically transform the tumor into a resectable state. The current significance of transformation therapy is to reduce tumor volume and stage to achieve radical resection, eliminate micrometastases, and prevent a postoperative recurrence. There are few studies on the transformation therapy of esophageal squamous cell carcinoma. We plan to conduct a prospective, single-center, single-arm phase II clinical study of the safety and efficacy of tislelizumab combined with chemotherapy in the treatment of T4a/N3 esophageal squamous cell carcinoma.

Eligibility Criteria:
Inclusion Criteria:

1. Histologically confirmed esophageal squamous cell carcinoma;
2. Unresectable cT4a/N3(stage ⅣA) (AJCC 8 TNM classification);
3. Have a performance status of 0 or 1 on the ECOG Performance Scale;
4. Age 18-75 years old, both men and women;
5. Be willing and able to provide written informed consent/assent for the trial;
6. Demonstrate adequate organ function, all screening labs should be performed within 10 days of treatment initiation;
7. Female subjects of childbearing potential should have a negative urine or serum pregnancy within 72 hours before receiving the study medication's first dose. If the urine test is positive or cannot be confirmed as unfavorable, a serum pregnancy test will be required;
8. Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion through repeated biopsies. Newly acquired is defined as a specimen obtained up to 4 weeks (28 days) prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from the Sponsor.

Exclusion Criteria:

1. Prior therapy (operation, radiotherapy, immunotherapy, or chemotherapy) for esophageal cancer;
2. Ineligibility or contraindication for esophagectomy;
3. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug;
4. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with the use of disease-modifying agents, corticosteroids, or immunosuppressive drugs);
5. Has severe hypersensitivity and adverse events (≥Grade 3) to any PD-1/PD-L1 inhibitors.
Exercise, Statins, and the Metabolic Syndrome

Here we tested if statins or exercise plus statins had a greater capacity to lower metabolic syndrome risk factors in sedentary individuals with at least 2 metabolic syndrome risk factors. We also examined if statins impacted exercise response for mitochondrial content in muscle or aerobic fitness.

OBJECTIVES: Determine if simvastatin impairs exercise training adaptations.

BACKGROUND: Statins are commonly prescribed in combination with therapeutic lifestyle changes, including exercise, to reduce cardiovascular disease risk in patients with the metabolic syndrome. Statin use has been linked to skeletal muscle myopathy and impaired mitochondrial function, but it is unclear whether statin use alters adaptations to exercise training.

METHODS: We examined the effects of simvastatin on changes in cardiorespiratory fitness and skeletal muscle mitochondrial content in response to aerobic exercise training. Sedentary overweight or obese adults with at least 2 metabolic syndrome risk factors (defined according to National Cholesterol Education Panel Adult Treatment Panel III criteria) were randomized to 12 weeks of aerobic exercise training or to exercise in combination with simvastatin (40 mg per day). The primary outcomes were cardiorespiratory fitness and skeletal muscle (vastus lateralis) mitochondrial content (citrate synthase enzyme activity).

Eligibility Criteria:
Inclusion Criteria:

* Sedentary metabolic syndrome subjects will be 25-59 y of age
* overweight to Class I or II obese (BMI 25-39 kg/m2) men and women
* 2 of 4 other characteristics of the metabolic syndrome including fasting glucose of 100 to 125 mg/dl; waist circumference greater than 102 cm in men and 88 cm in women, serum triglyceride concentration greater than 150 mg/dl, HDL-C concentrations less than 40 mg/dl in men and 50 mg/dl in women, and blood pressure greater than 130/85 mmHG
* Women must be taking birth control or be postmenopausal.

Exclusion Criteria:

* Diagnosed cardiovascular disease or diabetes or disease
* Symptoms that could alter their ability to perform exercise
* Fasting blood glucose of greater than 126 mg/dl
* Smoking
* Taking any medications or supplements (e.g., statins, fibrates, metformin, thiazolidenediones, anti-hypertensives (ACE-inhibitors and angiotensin blockers) which could affect blood lipids or insulin sensitivity.
* Women who are pregnant or plan to become pregnant during the duration of the study
* Individuals exercising regularly (more than one 30 min session per week)
* Individuals with an orthopedic limitations for walking.
* Report any allergies to the medications (statins, lidocaine)
A Trial Of Gemcitabine Plus Paclitaxel And Gemcitabine Plus Docetaxel In Metastatic Breast Cancer

The combination of docetaxel and gemcitabine has shown significant activity in patients with metastatic breast cancer. Several studies have activity in patients of multiple lines of therapy, including patients that have been treated with prior taxane therapy. Overall responses have ranged from 30% to 79%. The major side effects of the combination chemotherapy have been neutropenia, anemia, asthenia, neuropathy, nausea, mucositis, and neutropenic fever


Eligibility Criteria:
Inclusion Criteria:

* Advanced or metastatic breast cancer
* Disease that can be measured by the physician or radiologic test.
* May have had one chemotherapy treatment for advanced or metastatic disease.
* Patients may have received any prior adjuvant chemotherapy, including taxane containing regimens, provided this treatment was completed at least 6 months prior to enrollment.
* Patients may have received prior hormone therapy or immunotherapy.

Exclusion Criteria:

* Patients with only non-measurable disease
* Cancer that has spread to the brain
* A patient who received a taxane with metastatic disease.
* Pregnancy
* Patients who received prior gemcitabine
Prediction of pCR by Preoperative Biopsy in Breast Cancer With cCR After Neoadjuvant Chemotherapy.

The purpose of this study is to evaluate the ability of preoperative biopsy to predict correctly pathologic complete response in breast cancer patients with complete clinical response after neoadjuvant chemotherapy.

Breast cancer patients who received neoadjuvant chemotherapy and is predicted to have achieved pathologic complete response (pCR) on MRI will enrolled. The enrolled patients will undergo either US-guided multiple core needle biopsy or US-guided vacuum-assisted biopsy of the tumor bed where it had been marked with an indicator (clip). The patient will undergo subsequent wide excision of the tumor bed. Histopathologic findings of the biopsy and the surgical specimen will be compared for pCR, and the ability of preoperative biopsies to predict pCR will be evaluated.

Eligibility Criteria:
Inclusion Criteria:

Patients

* with unilateral primary cancer pathologically confirmed before neoadjuvant chemotherapy (NAC)
* who received NAC
* with detectable lesion / clip marker on ultrasound
* with cT1-T3 tumors
* clinical and imaging complete or near-complete response on MRI
* with informed consent

Exclusion Criteria:

* Multifocal cancer
* Residual microcalcification
* Contralateral breast cancer
Safety of Preoperative Carbohydrate Loading in Diabetic Patients

The purpose of this study is to investigate the safety of preoperative carbohydrate loading in diabetic patients undergoing general anesthesia


Eligibility Criteria:
Inclusion Criteria:

* Elective surgery
* Type 2 diabetes mellitus on oral hypoglycemic agents
* American Society of Anesthesiologists physical status 2 or 3
* Ages 18 or more
* Approve to participate

Exclusion Criteria:

* Ambulatory surgery
* BMI \>35
* History of gastric or esophagus surgery
* History of GERD, dyspepesia or
* Anticipated difficult intubation (previous III or more Cormack and Lehane's grade, Mallamgrade, Mallampati scpati scoreore III or moreIII or more, propro/retro/retrognathism, gnathism, thyromental distance\<6.5cm, thyromental distance\<6.5cm, limited mouth openinglimited mouth opening)
To Evaluate the Effect of AZD1722 on the Pharmacokinetics of Oral Midazolam in Healthy Volunteers

A Study to Evaluate the Effects of oral repeated doses of AZD1722 on the Pharmacokinetics of Oral Midazolam in Healthy Volunteers

A Phase 1, Single-center, Fixed-sequence, Open Label Study to Evaluate the Effect of Oral Repeated Doses of AZD1722 on the Pharmacokinetics of Oral Midazolam in Healthy Volunteers

Eligibility Criteria:
Inclusion Criteria:Have a body mass index (BMI) ≥18 and ≤30 kg/m2 and weigh at least 50 kg and no more than 100 kg. Females of non-childbearing potential must be postmenopausal defined as amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments and follicle stimulating hormone (FSH) levels in the postmenopausal range or documentation of irreversible surgical sterilization by hysterectomy, bilateraloophorectomy or bilateral salpingectomy but not tubal ligation

Females of childbearing potential must have a negative pregnancy test at screening, Day -1, and Day 14 and must not be lactating and use effective contraceptive methods to avoid pregnancy during the treatment period

Male healthy volunteers with a partner of childbearing potential must agree to avoid fathering a child, and refrain from donating sperm, from the first day of dosing until at least 3 months after last dose of the investigational product, and therefore be either sterile or agree to use approved methods of contraception

Exclusion Criteria:

* History of any clinically significant disease or disorder which, in the opinion of the principal investigator, may either put the healthy volunteer at risk because of participation in the study, or influence the results or the healthy volunteer's ability to participate in the study. History or presence of GI, hepatic or renal disease including GI surgery other than appendectomy or any other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs. Loose stools (BSFS of 6 or 7) ≥2 days in the past 7 days before investigational product administration. Use of medications that are known to affect stool consistency and/or GI motility, including fiber supplements, anti-diarrheals, prokinetic drugs, enemas, probiotic medications or supplements, or salt or electrolyte supplements containing sodium, potassium, chloride, or bicarbonate formulations during the past 7 days before the investigational product administration. Use of any prescribed or non-prescribed medication including antacids, analgesics other than paracetamol/acetaminophen, herbal remedies, vitamins and minerals during the 2 weeks prior to the first administration of investigational product or longer if the medication has a long half-life. Use of drugs or substances with enzyme-inducing properties within 4 weeks prior to the first administration of investigational product.
Effect of Lactobacillus Gasseri DSM 27123 on Functional Constipation in Healthy Women

The primary objective is to determine the change in frequency of complete spontaneous bowel movements (CSBMs) after 4 weeks of oral supplementation with Lactobacillus gasseri DSM 27123 in healthy adult women with functional constipation.

Subjects to complete study diaries, number of SBM, CSBM, form of faeces (according to the Bristol Stool Form scale), pain during defecation (according to the visual analogue scale \[VAS\] 0-100), time spent at each evacuation, episodes of faecal incontinence, number of ingested capsules of investigational product will be recorded daily by the subjects

Eligibility Criteria:
Inclusion Criteria:

The subjects have to meet all of the following criteria to be eligible to enter the study:

1. Willing and able to provide informed consent
2. Women aged 18-49 years at Visit 1
3. BMI ≥18 and ≤29 at Visit 1
4. Suffering of functional constipation as defined by the Rome III criteria for functional constipation
5. Comply with the requirement not to use any other probiotic products from Visit 1 and throughout the study period
6. Not pregnant or breastfeeding
7. Using adequate contraceptive measures
8. Ability to understand and comply with the requirements of the study, as judged by the Investigator

Exclusion Criteria:

1. Hypersensitivity or allergy to the investigational product, to chemically related products or to comparator/placebo
2. Well-known, organic cause of constipation
3. Anorectal pathology
4. Previous gastrointestinal surgery
5. Any alarming symptoms (i.e. rectal bleeding, weight loss, jaundice) as judged by the Investigator
6. Spinal anomalies and injuries
7. Use of antibiotics within 4 weeks prior to Visit 1
8. Use of products containing probiotics more than once a week in the previous 3 weeks
9. Mental or behavioural disorders as judged by the Investigator
10. Food allergy
Exercise Device in Total Knee Arthroplasty

Total knee arthroplasty is performed in patients with advanced stages of osteoarthritis who can not respond to conservative treatment, in order to reduce pain, increase range of motion, and improve function and quality of life. Continuous passive motion device continues to be used in many clinics, although it has been shown that there is no effect in total knee arthroplasty rehabilitation. The aim of the study was to assess the clinical effects of the knee exercise device on pain, ROM and function and quality of life in total knee arthroplasty rehabilitation.

Volunteers with total knee arthroplasty according to the criteria of inclusion, who will be operated in Istanbul University Istanbul Medical Faculty Orthopedics and Traumatology Department will be included this study. Participants will be randomly allocated 2 groups: easy-flex group and traditional exercise group. Exercise group will be treated with the traditional exercise program and the Easy-Flex group will be treated with the Easy-Flex device in addition to the traditional exercise program.

Eligibility Criteria:
Inclusion Criteria:

Patients with TKA surgery due to the diagnosis of knee OA Between the ages of 45-80 years Patients with no difference over 5 cm in the extremity before and after surgery

Exclusion Criteria:

Revision TKA, Previous unicompartmental arthroplasty or tibial osteotomy, Hemophilia, Uncontrolled hypertension Rheumatic diseases, Lower extremity fractures and tumors, Neurological diseases leading to muscle weakness in the lower limbs, Patients with emotional and cognitive problems
Vascular Effect of Estrogens Versus Placebo Evaluated by Flow-mediated Dilatation of Brachial Artery

The aim of this study is to evaluate the vascular effects of estrogens on climacteric women measured by flow-mediated evaluation of the brachial artery using high resolution ultrasound and compare to placebo.

The interruption of the secretion of sex steroids that occurs after menopause, determines a change in vascular pattern at various levels. As a result, several side effects might appear and interfere with women's quality of life and health. The use of hormone replacement therapy has contributed to the improvement in these effects. It has been observed vascular beneficial effects of sex steroids in premenopausal women, and of hormone replacement therapy (HRT) in climacteric women, on the central retinal arteries. The objective of this study is to evaluate the effects of conjugated equine estrogen on flow-mediated dilation of the brachial artery.

Eligibility Criteria:
Inclusion Criteria:

* Women without menstrual cycles within the last 12 months and FSH \> 30IU/L
* Healthy women
* Women that were not using drugs with potential vascular effect within the last 1 year
* Women that never used hormone replacement therapy

Exclusion Criteria:

* Smoking
* Blood Pressure \> 160/90 mm Hg.
* Breast and or endometrial cancer
* History of acute myocardial infarction
* Diabetes
* Vaginal bleeding of any origin
* Hepatic disease
* Thrombophlebitis or thromboembolic disorders
Retrieval Study and Histological Examination Of A Hip Femoral Components With Hydroxyapatite Coatings

Retrieval study and histological examination of BiMetric Femoral Components with hydroxyapatite coatings.

A single type of femoral component with 3 different HA coatings will be evaluated in this study. Patients with fractured neck of femur requiring hemi-arthroplasty will be recruited. Safety and performance of the device will be determined by adverse events (device related or non-related), survival and histological exam.

Eligibility Criteria:
Inclusion Criteria:

* Fractured neck of femur requiring hemi-arthroplasty. Selection of subjects for this evaluation should include the following considerations:-.
* A likelihood of obtaining relief of pain and improved function.
* Full skeletal maturity.
* Ability to follow instructions.
* Good general health for age.
* Willing to return for follow-up evaluations .
* No bias to sex.

Exclusion criteria:

• None
Aripiprazole in Body Focused Repetitive Behaviors

This study is 6 weeks long and involves subjects taking aripiprazole or placebo. If they are randomly assigned to the aripiprazole arm and are eligible to participate in the study, they will begin by taking 5mg once daily of aripiprazole for two weeks, then 10mg once daily for the remaining three weeks. Efficacy and safety measures will be performed at each visit. Participants will be randomized to receive either aripiprazole or placebo on a 1:1 basis. This blinding will be maintained by the IDS pharmacy at the University of Chicago.

The goal of the proposed study is to evaluate the efficacy and safety of aripiprazole in 100 subjects with DSM-5 trichotillomania (TTM) or skin picking disorder (SPD).

The hypothesis to be tested is that aripiprazole will be effective and well tolerated in patients with BFRBs (trichotillomania or skin picking disorder) compared to placebo. The proposed study will provide needed data on the treatment of disabling disorders that currently lack a clearly effective treatment.

This will be one of few studies assessing the use of pharmacotherapy for the treatment of TTM and SPD in adults. Assessing the efficacy and safety of aripiprazole will help inform clinicians about additional treatment options for adults suffering from this disorder.

Eligibility Criteria:
Inclusion Criteria:

1. Men and women age ≥18 years
2. current DSM-5 trichotillomania or skin picking disorder; and
3. Ability to understand and sign the consent form.

Exclusion Criteria:

1. Unstable medical illness based on history or clinically significant abnormalities on baseline physical examination
2. Current pregnancy or lactation, or inadequate contraception in women of childbearing potential
3. Subjects considered an immediate suicide risk based on the Columbia Suicide Severity rating Scale (C-SSRS) (www.cssrs.columbia.edu/docs)
4. Past 12-month DSM-5 diagnosis of psychosis, bipolar disorder, mania, or a substance or alcohol use disorder
5. Illegal substance use based on urine toxicology screening
6. Stable dose of medications for at least the past 3 months
7. Previous treatment with aripiprazole
8. Cognitive impairment that interferes with the capacity to understand and self-administer medication or provide written informed consent
Influence of Aging on Perioperative Methadone Dosing

Increasingly, elderly patients undergo anesthesia and surgery. Methadone is a great opioid for perioperative pain management, however, to date there are no pharmacokinetic or pharmacodynamic studies that asses a methadone dose adjustment in the elderly patient. The present study is aimed to characterize the pharmacokinetic and pharmacodynamic age-related changes of methadone in the adult population and further to design reference dosing protocols for intraoperative methadone use according to patient age.

The subjects will be recruited from adult patients who undergo elective laparoscopic abdominal surgery at UC Christus Clinical Hospital (Santiago, de Chile). Patients will be randomly divided into four groups according to the dose of intravenous methadone to be administered during anaesthetic induction.

BIS-guided and standard general anaesthesia will be administered with routine monitoring. Methadone will be administered once the patient is intubated and has hemodynamic stability. The only opioids that patients will receive will be remifentanil and methadone.

Upon admission to the Post-anesthesia care unit, the patient is given a Patient-Control Analgesia pump for intravenous administration of morphine. Clinic evaluations will be carried out periodically and blood samples for measurement of plasma methadone will be taken at different times. Samples will be analyzed using high-performance liquid chromatography spectrofluorometric method. The data obtained will be collected in a form within the REDCAP application, to subsequently generate an encrypted database. Groups will be compared regarding pain score, drugs used, opioid consumption, side effects, time of recovery, and patient satisfaction.

One, two and three-compartment linear models will be used to fit the plasma methadone concentration data over time. Models are parameterized in terms of elimination clearance, compartment distribution clearance, central volume and peripheral volume of distribution, as appropriate. The use of rescue morphine in the Post-anesthesia care unit will be used as a measure to relate the methadone dose (mg/kg) with the analgesic efficacy using an EMAX model. The data will be modelled using NONMEM VII. A proportional term will be used for variability between subjects. Additive and proportional terms will be used to characterize the unknown residual variability.

Sample size calculations were estimated using a simulation-based approach and previous work with a similar methodology. To achieve an adequate representation of all age groups 60 patients will be required, distributed among 20 patients between 18 and 40 years, 20 patients between 41 and 65 years, and 20 patients\> 65 years.

Eligibility Criteria:
Inclusion Criteria:

1. Over 18 years.
2. ASA I, II or III.
3. Laparoscopic Abdominal Surgery.

Exclusion Criteria:

1. BMI\> 35
2. Use of opioids up to 5 days before surgery.
3. Acute Liver Failure or Chronic Liver Damage Child C.
4. Kidney damage with creatinine clearance estimated by Cockcroft-Gault formula \<60 ml/min.