Dax

Myeloproliferative Neoplasms MPN are blood cancers linked to a higher risk of blood clots. This research focuses on understanding how the presence of a genetic mutation called JAK2V617F in different blood cell types and endothelial cells relates to the risk of developing these clots. Researchers aim to identify specific patterns of this mutation in various cell populations that might help predict which patients are at higher risk for thrombosis. The study involves 120 patients diagnosed with either Polycythemia Vera PV or Essential Thrombocythemia ET. Blood samples will be collected to isolate platelets, red blood cells, granulocytes, and endothelial cells. Using digital PCR technology, the level of the JAK2V617F mutation will be measured in these cells. Patients with or without a history of thrombosis and different types of thrombosis will be compared to identify any associations with the mutation profiles. Participants will be involved at the time of diagnosis or within one year of diagnosis before starting cytoreductive treatment. Researchers will evaluate the mutation level in different blood cells and endothelial cells, assess the type of MPN, and measure the risk score for thrombosis. The main outcome is the history of thrombosis at diagnosis. This observational study does not involve treatment but collects blood samples and clinical data to better understand thrombosis risks in MPN patients.

Researchers are studying ICU Acquired Weakness by evaluating whether early sitting out of bed in an arm-chair position improves functional recovery in patients who are ventilated in intensive care. This trial compares this early armchair positioning to a conservative strategy of sitting in bed, aiming to clarify if the armchair is essential for improving muscle and functional outcomes, as current guidelines do not strongly recommend this practice. Participants who have been awake with a certain alertness level RASS score between -1 and 1 for over 12 hours are randomly assigned to either daily chair sessions lasting at least 30 minutes or to no chair positioning. The chair sessions continue until ICU discharge or day 28, with careful monitoring of tolerance and a maximum session duration of 4 hours. The study follows patients through their ICU stay to assess recovery. During the study, researchers assess functional levels at ICU discharge or day 28, along with mobility scales, muscle strength scores, length of ICU and hospital stays, ventilator-free days, and mortality rates up to six months. Patients are monitored closely for safety and recovery progress throughout their ICU stay, with data collected to understand the impact of early armchair positioning on their health and function.

Researchers are evaluating the timing of antibiotic therapy for patients suspected of having non-severe ventilator-associated pneumonia VAP in intensive care units. This study compares immediate antibiotic treatment started right after respiratory sampling with a conservative approach that waits for microbiological confirmation before beginning treatment. Delaying antibiotics may reduce unnecessary use and antibiotic resistance but might risk worse outcomes if infection is present. The study is a randomized controlled trial led by Nantes University Hospital to better understand these strategies in patients without severe symptoms like septic shock or severe respiratory distress. The trial has two groups the immediate strategy group receives empiric antibiotics within one hour after randomization based on clinical judgment and local protocols. If respiratory samples later test negative, antibiotics are stopped if positive, targeted therapy continues for seven days. The conservative strategy group does not start antibiotics until respiratory sample cultures or PCR results confirm infection. If confirmed, appropriate antibiotics are administered for seven days without waiting for susceptibility testing. Both approaches focus on managing suspected VAP to balance timely treatment and antibiotic stewardship. Participants will be monitored from day 0 to day 28, with assessments including mortality and mechanical ventilation status at day 28 as the main outcome. Additional evaluations cover organ failure scores, lung infection scores, duration of ventilation, use of supportive therapies, hospital and ICU stay lengths, infection incidence, antibiotic use, and cost-utility analysis up to day 90. The study involves informed consent, respiratory sampling within two hours of suspicion, and excludes patients with severe VAP or significant immunosuppression. This comprehensive follow-up aims to clarify the impact of antibiotic timing on patient outcomes and antibiotic resistance in ICU settings.

Researchers are investigating the best noninvasive respiratory support method for patients in intensive care units ICUs who develop respiratory failure after planned removal of their breathing tube extubation. This condition affects about 20% of ICU patients, and many require reintubation, which is linked to high mortality rates. The study aims to compare whether alternating non-invasive ventilation NIV with high-flow nasal oxygen reduces death rates compared to high-flow nasal oxygen alone in these patients. The trial is a multicenter, randomized, controlled study where patients with post-extubation respiratory failure are assigned to one of two groups. One group receives continuous high-flow nasal oxygen treatment for 48 hours, while the other group receives NIV alternating with high-flow nasal oxygen during the same period. NIV involves pressure-support breathing with specific settings to help patients breathe, and the study ensures balance in patient groups based on carbon dioxide levels in the blood. Participants will be closely monitored with assessments including timing of death, reintubation events, days without ventilator use, length of ICU and hospital stay, and mortality at different time points up to 90 days. The main outcome measured is death rate 28 days after respiratory failure onset. The study includes clinical evaluations and blood gas tests to guide treatments and decisions. Participation duration includes the initial 48-hour treatment period and follow-up assessments extending to 90 days.

Squamous cell carcinoma of the anus is a rare but increasingly common cancer, often linked to human papillomavirus HPV. For early-stage tumors, combined radiotherapy and chemotherapy with 5FU and mitomycin-C provide good outcomes, but advanced tumors have a poor prognosis with a high relapse rate. Researchers are studying a new approach combining induction chemotherapy with docetaxel, cisplatin, and 5FU mDCF followed by standard chemoradiotherapy to improve treatment results for locally advanced anal cancer T3-4 or N1. This is a randomized phase 3 trial comparing this new strategy to the current standard treatment. The study includes two groups one receives the usual chemoradiotherapy, which involves 33 radiotherapy sessions over 6.5 weeks combined with mitomycin-C and capecitabine chemotherapy taken on radiotherapy days. The other group starts with 4 cycles of mDCF chemotherapy given every two weeks before receiving the same chemoradiotherapy as the control group. Radiotherapy uses intensity-modulated external irradiation with a targeted boost to the tumor and involved lymph nodes. Participants will be followed after treatment with check-ups at 8 weeks, then every 4 months for two years, and every 6 months in the third year. Follow-up includes clinical exams and imaging scans CT and MRI. The main measure of success is disease-related event-free survival two years after treatment. Other outcomes include overall survival, colostomy-free survival, treatment side effects, tumor response, and quality of life. The total study duration for each participant may extend over several years including this follow-up period.

Infected pilonidal sinus is a common condition that occurs more frequently in men, usually between the ages of 15 and 30. This trial evaluates a new radiofrequency treatment using the Fistura procedure for infected pilonidal sinus to measure its safety, effectiveness, and patient satisfaction. The study aims to address the limitations of traditional open wound surgery and newer laser techniques by using radiofrequency thermocoagulation, which has been used safely in treating anal fistulas. Participants will receive the radiofrequency treatment with fibers adapted for the size of the pilonidal sinus cavity. This method is believed to better destroy granulation tissue and assist healing. The study will monitor safety within 15 days after treatment and evaluate treatment efficiency and patient satisfaction at 1 month and 6 months post-treatment. Medical leave length will also be recorded. Participants will be assessed before and after treatment, including safety checks shortly after the procedure and follow-up visits to measure pain, healing, and satisfaction. The primary outcome focuses on safety within 15 days after treatment. Secondary outcomes include treatment efficacy at 6 months, pain levels, duration of medical leave, and satisfaction surveys. The total study period includes initial treatment and monitoring over 6 months to understand the treatments impact.

Researchers are evaluating treatments for community-acquired pneumonia CAP, especially in patients admitted to intensive care units ICUs. This trial also adapts to study treatments for respiratory pandemics like COVID-19. The goal is to determine which treatment strategies improve outcomes for patients with severe pneumonia, using a flexible, ongoing approach that can test multiple therapies simultaneously and update as new information becomes available. Participants receive different treatment strategies based on random assignment to study groups. Treatments include various antibiotics, steroids, antivirals, immune modulators, anticoagulation methods, and ventilation strategies. Some treatment options have been closed to recruitment, reflecting the trials adaptive nature. The trial includes several domains targeting specific infections such as influenza and COVID-19, with dosing and duration guided by clinical practice and local guidelines. During the study, participants are monitored closely with assessments including survival up to 90 days, days alive without organ support in ICU, ICU and hospital length of stay, ventilator-free days, organ failure-free days, and quality of life up to 6 months. Researchers collect detailed data on patient outcomes, organ support needs, and hospital discharge status. The study runs until February 2028, with ongoing evaluation to improve pneumonia treatment strategies in ICU settings and during respiratory pandemics.

Systemic sclerosis SSc is a rare autoimmune disease that causes skin thickening and can affect internal organs, leading to serious health issues. This research evaluates the safety and effectiveness of itacitinib, a drug targeting specific pathways involved in SSc, particularly the JAK-STAT pathway linked to fibrosis and inflammation. The study focuses on adults with diffuse SSc, a severe form with significant skin and organ involvement. Participants are randomly assigned to receive either 200 mg of oral itacitinib daily or a matching placebo for 360 days. The study is a phase II, randomized, controlled trial with quadruple masking to compare outcomes between these two groups. The trial assesses treatment effects on skin thickening and disease activity over the course of one year. During the study, participants undergo regular assessments including skin scoring modified Rodnan skin score, disease activity evaluations, and quality of life questionnaires at multiple time points up to 360 days. Safety is monitored through adverse event tracking and laboratory tests. The main outcome measured is the change in skin thickness after 360 days of treatment, helping researchers understand the potential impact of itacitinib on systemic sclerosis.

Researchers are studying the potential benefits of outpatient care for patients with acute uncomplicated appendicitis treated by laparoscopic appendectomy. This research aims to compare outpatient care with conventional hospital care to see if outpatient care is not worse in terms of overall morbidity and mortality within 30 days after surgery. The study is motivated by the need to optimize care pathways, reduce hospital stays, improve patient satisfaction, and lower healthcare costs, especially important during the COVID-19 pandemic. The trial compares two treatment groups one receiving ambulatory appendectomy where surgery is done in an outpatient surgery unit and patients are discharged the same day, and the other receiving conventional appendectomy where surgery occurs in the digestive surgery department and patients stay overnight for observation before discharge. The study evaluates outcomes up to 30 days after surgery, including hospital stay length, rehospitalization rates, complications, re-interventions, patient satisfaction, quality of life, and economic impacts. Participants will undergo assessments before and after surgery, with monitoring of clinical outcomes, patient satisfaction, and quality of life at 7 and 30 days post-operation. Researchers will also track safety, the rate of conversion from outpatient to conventional care, and costs associated with each care pathway. The total study participation includes follow-up for 30 days after surgery to assess the main and secondary outcomes.

Researchers are investigating the best way to manage treatment withdrawal of denosumab Dmab in women with postmenopausal osteoporosis. Denosumab is an effective treatment, but stopping it can cause a rebound effect, including increased bone turnover markers, loss of bone density, and a higher risk of vertebral fractures. This study aims to compare two strategies using zoledronate ZOL infusions to reduce these rebound effects after Dmab withdrawal. Participants receive an initial ZOL infusion six months after stopping denosumab. One group receives a second ZOL infusion guided by biomarker levels crosslaps if these reach a certain threshold within one year. The other group follows a standard treatment with a potential rescue second infusion at month 12 if there is an unfavorable outcome or high risk of fractures. This open-label randomized trial tests whether biomarker-driven additional treatment offers better protection against bone loss. During the study, participants will have bone mineral density BMD measured in the lumbar spine and hip at baseline, one year, and two years. Bone turnover markers and fractures will also be monitored regularly up to two years. The main outcome is maintaining lumbar BMD after one year of zoledronate treatment. Safety and treatment response will be assessed throughout the study duration, which includes follow-up visits at months 3, 6, 9, and 12.