cyrilzakka/clinical-trials huggingface dataset:
Reproductive Capacity and Iron Burden in Thalassemia

The improved long-term survival of thalassemia major (TM) patients has resulted in increased focus on the ability to preserve fertility. While the association of iron toxicity with vital organ dysfunction, heart and liver, has been extensively investigated, the correlation of reproductive capacity and extent of iron overload is not well understood. Despite remarkable progress in methodology for prediction of reproductive status and intervention for preserving fertility, implementation in thalassemia is lacking.

The investigators hypothesize that iron toxicity to the anterior pituitary occurring in the process of transfusional iron loading is directly associated with a decline in gonadal function. The investigators expect pituitary MRI measurements of iron deposition as well as markers of oxidative damage to correlate with the functional studies of pituitary-gonadal axis performed in this study. This cross sectional study will examine the relation of pituitary iron deposition and pituitary volume; serum iron and oxidative stress measures, liver iron concentration (LIC), cardiac iron and chelation adequacy with pituitary and gonadal reproductive hormone levels (and spermatogenesis in adult male patients), in order to better define the association of iron burden and chelation patterns with fertility potential, in thalassemia patients with iron overload. The study will assess whether the current chelation treatment regimens, in particular during the pubertal developmental age, are adequate for preserving fertility and could lead to improved chelation routines for preventing the high prevalence of compromised fertility. In addition, by utilizing state-of-the-art markers for fertility status, findings from this study may improve current methods for screening for hypogonadism and reproductive potential and allow earlier intervention.

The investigators propose to examine 26-30 patients, 12 years and older, with measures of fertility potential, and correlate them to their current iron burden parameters and to the cumulative iron effect as indicated by past iron overload patterns and chelation history.


Eligibility Criteria:
Inclusion Criteria:

* Transfusion-dependent\* females and males with thalassemia (any genotype) who are 12 to 45 years of age.
* History of at least 5 years of chronic transfusion (defined as ≥ 8 transfusions/year) (Age of initiation of transfusions does not matter)
* Any pubertal stage.
* Liver iron evaluated by SQUID, MRI or liver biopsy within 12 months prior to enrollment in the study.
* Need to be able to stop hormonal therapy for 3 weeks (males) and one month (females) prior to study enrollment.

Exclusion Criteria:

* Pregnant or lactating during study enrollment
* Unable to obtain liver iron concentration within 12 months prior or 6 months after study entry.
The Impact of a 48-hour Fast with or Without Exercise on Immune Cell Metabolism and Glycemic Control in Healthy Active Adults

Many individuals engage in fasting for its purported health benefits but the effects of fasting on immune cell and whole body metabolism are not well understood in humans. Moreover, how exercising during a prolonged fast impacts immunometabolic outcomes is unclear. This study will determine how a 2 day fast - performed with or without daily exercise - impacts immune cell bioenergetics, immune cell function, and whole-body glycemic control in healthy active individuals.

Participants will perform two, 48-hour fasts separated by 5 days while wearing a continuous glucose monitor to measure glycemic responses. The order of the trials will be randomized for each participant. The two trials will include an exercise condition (FAST+EX) and a control, non-exercise condition (FAST). During the FAST+EX trial, participants will perform 60 minutes of cycling on each of the two days of the fast. Each bout of exercise will be 60 minutes in duration and consist of 50 minutes of cycling at 60% of predicted heart rate reserve (HRR) followed by 5 x 1-minute intervals at 90% of predicted HRR with 1-minute of passive recovery between each interval. During the FAST trial, participants will be asked to refrain from any structured exercise during the days of the fast. To start the trial, participants will arrive at the lab following an overnight fast. They will consume a standardized meal replacement (Ensure Plus Calories) and blood will be drawn 2 hours post-ingestion. Participants will come to the lab 24 and 48 hours later for subsequent blood draws prior to breaking their fast with the same standardized meal replacement. Another blood sample will be taken 2 hours post-prandial. Participants will be asked to replicate food consumption in each condition for the 24-hour period after they break their fast, and consume the same standardized meal replacement on the morning following the completion of each fast to measure free-living glycemic control 24-hours after a fast performed with or without exercise. There will be a five-day wash out period in between the completion of both trials for all participants.

Eligibility Criteria:
Inclusion Criteria:

* Aged between 19 and 35 years.
* Physically active (engaging in ≥150 minutes of weekly moderate to vigorous physical activity).

Exclusion Criteria:

* History of cardiometabolic diseases or inflammatory diseases (e.g., chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, cardiovascular disease).
* Individuals currently following a ketogenic diet, low-calorie diet, periodic fasting regimen, or consuming ketogenic supplements (e.g., exogenous ketone drinks).
* Cigarette/vaping smoking.
* Physical limitation that will impair the ability of the participant to perform exercise.
* Individuals having a body mass index (BMI) over 30 kg/m2.
* Cancer diagnosis in the past 5 years.
* Taking anti-inflammatory drugs (e.g., ibuprofen, aspirin, naproxen).
* Being unable to read or communicate in English.
A Study Evaluating the Safety of Elexacaftor/Tezacaftor/Ivacaftor in Participants With Cystic Fibrosis (CF)

The purpose of this study is to evaluate the safety and tolerability of elexacaftor (ELX)/tezacaftor (TEZ)/ivacaftor (IVA) in participants with CF who are 12 years of age or older.


Eligibility Criteria:
Key Inclusion Criteria:

* Completed study drug treatment in parent study (VX19-445-117 \[NCT04599465\] or VX20-445-126 \[NCT04969224\]), or had study drug interruption(s) in parent study but completed study visits up to the last scheduled visit of the treatment period in the parent study

Key Exclusion Criteria:

* History of drug intolerance in a parent study

Other protocol defined Inclusion/Exclusion criteria may apply.
Effect of Individualized PEEP on Postoperative Pulmonary Complication in Bariatrics

Ventilation with low tidal volume and high PEEP (positive end expiratory pressure) has been shown to improve oxygenation in patients with ARDS (acute respiratory distress syndrome). In obese patients undergoing laparoscopic bariatric surgeries, the risk of postoperative pulmonary complications (PPCs) increases significantly with general anesthesia. Previous studies have shown that protective lung ventilation strategies could improve intraoperative oxygenation and lung mechanics.

In this study would compare the effect of optimum individualized high PEEP versus standard PEEP - on postoperative pulmonary complications


Eligibility Criteria:
Inclusion Criteria:

* Patients were eligible for participation if the met the following criteria

  * Age between 18 and 60 years old.
  * Body mass index \> 40
  * Laparoscopic bariatric elective surgery under general anesthesia.
  * ARISCAT (Assess Respiratory Risk in Surgical Patients in Catalonia) score ≥ 45 . ARISCAT score is a clinically practical seven-factor scoring system to assess the risk of a composite PPC.

Exclusion Criteria:

* Previous lung surgery
* ASA status III or IV.
* Moderate to severe obstructive or restrictive lung disease .
* Persistant intraoperative hemodynamic instability .
* Need for postoperative mechanical ventilation
Transesophageal Echocardiography: Dysphagia Risk in Acute Stroke (T.E.D.R.A.S. Trial)

The prevalence of dysphagia in acute stroke patients undergoing transesophageal echocardiography (TEE) is unknown. The aim of this study was to assess for the first time whether TEE has a negative influence on swallowing in acute stroke patients.

Dysphagia is common in patients with acute stroke and deteriorates the overall outcome (1). Transesophageal echocardiography (TEE) is a routine examination in the diagnostic workup of stroke etiology. In cardiac surgery it is known as cause of postoperative dysphagia (2).

Using flexible endoscopic evaluation of swallowing (FEES) T.E.D.R.A.S., as a prospective, blinded, randomized and controlled study, includes patients in two groups in order to test the influence of TEE on swallowing in acute stroke: an intervention group and a control group. FEES is performed for analysis of swallowing in the intervention group (1) one day before TEE, (2) 2-4 hours after TEE, (3) 24 hours after TEE. In the control group FEES is performed on three consecutive days with TEE taking place any time after the last FEES. Validated scores assess dysphagia severity in both groups.

Eligibility Criteria:
Inclusion Criteria:

* acute stroke (max. 7 days post-onset) as displayed by a cranial computed tomography (CT) or magnetic resonance imaging (MRI)
* written informed consent either by patients themselves or by a legal representative
* indication for TEE

Exclusion Criteria:

* brain hemorrhage
* either pre-existing neurogenic dysphagia or
* head-and-neck cancer induced dysphagia
* dementia
* aphasia with an impairment in language comprehension
Exercise Dose and Nonalcoholic Fatty Liver Disease

The purpose of this research is to provide a better understanding of how exercise (walking) affects non-alcoholic fatty liver disease (NAFLD) in overweight people. NAFLD, which is common in obese people, occurs when the liver has too much fat.

Non-alcoholic fatty liver disease (NAFLD) affects about 33% of adults in the United States. The prevalence of NAFLD is four to five times higher in obese than lean persons and is associated with insulin resistance and the metabolic syndrome. Decreasing calorie intake and increasing physical activity has been recommended as primary therapy for NAFLD, but the independent effect of aerobic exercise is unknown. The current exercise guidelines for disease prevention and weight management range from 150 min/wk, recommended by the Centers for Disease Control and the American College of Sports Medicine, to 300 min/wk, recommended by the Institute of Medicine. However, it is not known whether aerobic exercise alone can improve NAFLD, and which recommended dose of exercise might have the most beneficial effects. The purpose of this proposal is to determine the effect of moderate intensity endurance exercise on: 1) hepatic fat content; 2) hepatic lipoprotein kinetics; and 3) plasma inflammatory markers. We hypothesize that aerobic exercise will decrease hepatic fat content, improve VLDL kinetics, and decrease inflammation in a dose-dependent fashion. The results from this study will help determine exercise guidelines for obese patients with NAFLD, and lay the groundwork for future studies evaluating the effects of exercise on metabolic diseases associated with obesity.

This proposal involves conducting a randomized controlled trial that will randomize obese subjects with NAFLD (\> 10% hepatic fat content) to one of two groups: Group 1 (Control, no exercise) and Group 2 (Moderate Intensity Aerobic Exercise- 150 min/wk to 300 min/wk of supervised exercise performed at 45-55% of O2 max).

Eligibility Criteria:
Inclusion Criteria:

* Age 18-65 with Nonalcoholic Fatty Liver Disease as determined by MRS

Exclusion Criteria:

* Medical History

  * Diabetes
  * Heart Disease
  * Asthma/Lung disease
  * Injury that prevents exercise
* Social history

  * Drinking
  * More than one drink per day
  * Binge drinking on the weekends (more than 3 or 4 drinks per weekend day)
* Smoking
* It's OK if they were a previous smoker, but they need to have quit more than 6 months ago
* Exercise

  * They must exercise less than one hour per week
  * Medications: must be on stable regimen of ANY medication for at least 3 months
* Beta-Blockers

  * Lipid/cholesterol lowering medications:
  * Oral hypoglycemics (anti-diabetes medications - some like metformin are indicated for pre-diabetes)
* Hormone replacement therapy
* If the woman is pre-menopausal, it is OK if she is on birth control as long as she has been on it over 3 months
* Weight history

  * Weight \<300 lbs
  * BMI 30 to 45
  * Weight stable - \<10lbs weight loss or gain in the last 3 months
PET on Surgery for Loco-regionally Recurrent Colorectal Cancer

The influence of Positron-Emission-Tomography (PET) on the surgical treatment of loco-regionally recurrent colorectal cancer (LRRCRC) remains obscure and deserves further investigation.

Loco-regionally recurrent colorectal cancer (LRRCRC) occurs in 4.0-11.5% of patients following treatment of primary colorectal cancer with curative intent, and can be categorized as peri-anastomotic, mesenteric/paracolic (nodal), retroperitoneal and peritoneal.1-4 In contrast to distant recurrences (e.g. liver, lung or bone metastasis), LRRCRCs is a less recognized clinical entity, although it is generally accepted that surgical resection remains the major treatment modality to provide the long-term survival for such patients.5-7 However, the value of resection for LRRCRC is obscure, given the role of surgical resection in treating LRRCRC has received comparatively little attention with a scant literature to draw upon when making treatment recommendations and no available consensus statements.8,9 Moreover, in clinical practice, it has been recognized that more than 50% of patients with recurrent colorectal cancer brought to the operating room for attempted curative surgery were unable to undergo the planned operation because more extensive disease than anticipated was discovered at laparotomy. Therefore, it has been suggested that a formal multidisciplinary team (MDT) discussion based on more precise diagnostic armamentariums be mandatory for more accurate evaluation of tumor burden and would allow curative surgery to be offered to a better-selected group of patients with recurrent colorectal malignancy10-14.

Remarkably, Positron-Emission-Tomography (PET) scans are now being widely used for the surveillance of patients having undergone curative resection for the primary colorectal cancer . Whole-body PET scanning in the patient with recurrent colorectal cancer has been reported to be more sensitive and accurate than Computed-Tomography (CT) and Magnetic-Resonance-Imaging (MRI). Moreover, PET is purported to be capable of differentiating among recurrent malignancy, scar, fibrosis, and necrosis, thus preventing the patients from futile surgery.15 With the above-mentioned reasons in mind, we then conducted this retrospective study to look at the efficacy of PET scan for directing surgery in patients with LRRCRC. We hypothesized that with the better diagnostic sensitivity and specificity, as compared to the conventional imaging methods (CT/MRI) in detecting recurrences of colorectal cancer, PET can positively affect the surgical decision-making and thus improve the treatment outcomes for patients with LRRCRCs.

Eligibility Criteria:
Inclusion Criteria:

i. patients with primary colorectal cancers undergoing R0 resection ii. Patients with final histopathologic reports documenting the pathologic Tumor-Node-Metastasis (pTNM) stage I, II, or III

Exclusion Criteria:

i. Patients with pTNM stage IV primary colorectal cancer ii. Patients with R1/2 resection
SYSTEMATIC SYMPTOM ASSESSMENT IN CANCER PATIENTS TREATED WITH IMMUNE CHECKPOINT INHIBITORS

Immune-related adverse events (irAEs) can be different in their onset, kinetics and presentation but unlike chemotherapy are seldom predictable. Toxicity can affect nearly any organ system and multiple presentations of rare but severe irAEs have been reported, highlighting the relevance of vigilant monitoring.

Although early detection and timely management of high grade or special interest irAEs (such as cardiac and neurological) is obvious, it is unclear whether early identification of less serious events can lead to clinical benefit. Furthermore, it is of the utmost importance to develop new tools which can increase identification of side effects. The current study investigates systematic symptom assessment through an electronic patient reported outcome tool and aims to define whether this can reduce the rate of serious irAEs.

Systematic collection of symptom information during immunotherapy treatment will be compared to usual care in locally advanced or metastatic lung cancer (NSCLC or SCLC) and surgically resected or advanced melanoma. Electronic survey will be administered every other day to report 14 common symptoms selected from the NCI-PRO-CTCAE TM library developed by the NATIONAL CANCER INSTITUTE (NATIONAL INSTITUTES OF HEALTH, Bethesda, Maryland) Italian version (NCI-PRO-CTCAETM ITEMS-ITALIAN-Item Library Version 1.0).

Eligibility Criteria:
Inclusion Criteria:

* Age ≥ 18 years old at time of signing Informed Consent Form
* Histologically documented diagnosis of locally advanced or metastatic lung cancer (NSCLC or SCLC), surgically resected or advanced melanoma
* Patients eligible for immunotherapy in any line of treatment, either alone or in combination with other immunotherapy drugs or with chemotherapy
* Signed Informed Consent Form
* Life expectancy ≥3 months
* ECOG Performance Status of ≤2
* Adequate hematologic and end-organ function, defined by laboratory test result by investigator's judgment
* Viral hepatitis screening:

  1. Negative hepatitis B surface antigen (HBsAg) test
  2. For patients with positive total HBcAb test, hepatitis B virus (HBV) DNA test is required
  3. For patients with positive HCV antibody test, hepatitis C virus (HCV) RNA test is required

Exclusion Criteria:

* Patients receiving immunotherapy at time of enrollment
* \> 1 grade adverse events from previous treatments
* Any uncontrolled symptom
* Clinically unstable brain metastases (i.e., symptomatic, not treated with RT and rapidly evolving)
Placebo Controlled Trial of a Titanium Dioxide Semiconductor Toothbrush on Mild-to-moderate Gum Disease

The effects on indices of gingivitis/periodontitis will differ between study arms in which the titanium dioxide semiconductor toothbrush is used, compared to an otherwise identical toothbrush with an inert resin core in place of the titanium dioxide semiconductor.

Organic acid producing anaerobic bacteria are implicated in the development and progression of gingivitis and periodontal disease (Brill, 1962; Kleinberg, 1974). The disease process manifests as periodontal inflammation and tissue destruction (Oliver et al, 1969). Although relatively crude methods are used for routine clinical diagnosis and monitoring of periodontal disease (eg, probing for gingival pocket depth and bleeding), sensitive and reproducible measures of periodontal disease have been validated (Oliver et al, 1969; Löe et al, 1965; Egelberg, 1964; Golub et al, 1976; Borden et al, 1977).

By the Lewis definition, an acid is an electron pair acceptor. In the presence of light \&/or electrical induction, valence electrons from a wetted titanium dioxide (TiO2) semiconductor will donate electron pairs to neutralize organic acids. Whereas a tooth surface is negatively charged, plaque has a net positive charge, and in part, ionic attraction contributes to the adherence of plaque to the tooth surface. Donating electrons to the plaque will alter polarity and diminish the ionic attraction between the plaque and the tooth surface (iontophoretic effect).

Thus, in addition to the established mechanical benefits of brushing, the flow of electron pairs for disrupting ionic bonding of plaque to the tooth surface and neutralizing bacterial organic acids, may confer an advantage over a conventional toothbrush (Hoover et al, 1992; Niwa et al, 1989; Kusunoki et al, 1986). There is some evidence that the electrons may also interact with bacterial coenzyme-A to have an antibacterial effect (Morioka et al, 1988; Onoda et al, 1996).

Eligibility Criteria:
Inclusion Criteria:

* 30 to 70 yrs of age
* mild-to-moderate periodontal disease
* dentulous

Exclusion Criteria:

* any unstable medical condition
* pocket depth \> 5 mm
Imaging Biomarker in Cancer Drug Induced ILD

Drug induced interstitial lung disease (DIILD) is caused by iatrogenic injury to the lung parenchyma and can be caused by over four hundred different drugs in humans. Diagnosing DIILD is a challenge for clinicians and radiologists as a positive diagnosis depends on exclusion of other causes including respiratory infection, occupational, recreational, and environmental exposures, specific respiratory disorders, and systemic diseases.

The aim of this study is to qualify an objective CT scoring system for DIILD assessment. In addition, the quantitative information obtained from CT scans with densitometry and texture analysis will be explored.


Eligibility Criteria:
Inclusion Criteria:

* Age ≥ 18 years
* World health organization (WHO) performance status 0-2
* Life expectancy \> 6 months
* Proven cancer diagnosis in a patient actively undergoing anti-cancer therapy
* New onset symptoms (e.g. cough, fever, dyspnoea, and hypoxia) at any time during or within 4 weeks of the last dose of anti-cancer treatment
* New onset radiological (CXR or CT) abnormalities within the lungs at any time during or within 4 weeks of the last dose of anti-cancer treatment (e.g. diffuse lung changes, infiltrative opacification in the periphery of the lung or ground glass changes) with a locally reviewed diagnosis of DIILD as the most likely explanation for the radiological abnormalities.
* Treatment for DIILD planned (e.g. drug withdrawal, interruption +/- supportive therapy including corticosteroids, oxygen, bronchodilators etc.). Concomitant treatment with antibiotics, anticoagulants etc. is permitted pending results of investigations for differential diagnoses.
* Able to undergo pulmonary function tests (at a minimum spirometry and gas transfer (DLCO))
* Patients enrolled on other anti-cancer investigational trials are permitted at investigator discretion
* Informed written consent obtained according to national/local regulations
* Women of child bearing potential (WOCBP) must have a negative serum (or urine) pregnancy test within 14 days before study registration

Exclusion Criteria:

* Clinically suspected or confirmed radiological features of any malignancy involving the lungs at the time of study registration
* Claustrophobia, or inability to undergo non-contrast CT examination
* Known or suspected non-drug related ILD (e.g. lung abnormalities due to other causes such as occupational exposure)
* Previous extensive thoracic surgery (e.g. lobectomy)
* Clinical, radiological or microbiological evidence of active lower respiratory tract infection
* Currently active, clinically significant heart disease, such as uncontrolled class 3 or 4 congestive heart failure defined by the New York Heart Association Functional Classification
* Any medical, psychological, sociological or geographical condition that could affect participation in the study and compliance with the study protocol