5-aminosalicylic acid (5-ASA) medications are first line treatment for mild to moderate Ulcerative Colitis (UC), comprise 81% of all UC prescriptions, and have a market share of 1.5 billion. However, despite 5-ASA frequency and optimization, 35% of patients fail induction therapy and 52% of patients fail to maintain remission at 12 months, requiring step up therapy to immunomodulators or biologics which have increased side effects and cost. This highlights a key challenge in UC which is to address the large inter- and intrapatient variabilities in both disease progression and variability in response to treatment. Chronotherapy is the timing of medical interventions according to the host circadian rhythms in order to optimize drug response and minimize toxicity, and is one explanation for the large variability in response to medications. The long-term objective of our research is to establish the hypothesis that is that appropriate time of day of administration of oral, once daily 5-ASA therapy in alignment with the host circadian rhythms will improve subclinical inflammation and microbial structure/function and increase mucosal 5-ASA levels. To test this hypothesis, In
response to the small R01 for pilot and feasibility clinical trials (PAS-20-160) and to test our hypothesis, we propose to conduct a six month, single center, randomized crossover pilot trial involving 60 subjects with inactive UC [Mayo score ≤2, endoscopic score 0-1] but subclinical inflammation [stool calprotectin > 50 mcg/g] on a stable dose of once daily 5-ASA medication. All subjects will be randomized to once daily 5-ASA medications two different times of the day: either between 06:00 – 10:00 h or 18:00 – 22:00 h. Three disease assessments will performed at: 1) enrollment just before randomization; 2) month 3, at the completion of first arm (condition 1), and 3) month 6, after completion of the second arm (condition 2). We will assess time impact of our chronotherapy protocol on: 1) subclinical inflammation (Aim 1): a) stool calprotectin; b) intestinal barrier integrity; and c) endoscopic/histology scores; 2) Microbiota: mucosal and stool microbiota structure and function (Aim 2); and 3) 5-ASA metabolism: a) increase mucosal levels of 5-ASA and b) mucosal NAT activity (Aim 3). In addition, optimal 5-ASA treatment (i.e., Aims 1-3) will depend upon host chronotype which will be monitored by validated questionnaires, rest-wake actigraphy, and urinary melatonin. The results of this innovative proposal will establish a key role for chronotherapy in the treatment of UC and provide pilot data for the future larger multicenter clinical trials. Chronotherapy will allow for a personalized medicine approach that incorporates circadian biology to improve efficacy and minimize intolerance in treatment of UC.

This study is a multicenter, randomized, double-blinded, placebo-controlled trial to evaluate the safety and efficacy of ExoFlo for the treatment of moderate-to-severe ARDS (Acute Respiratory Distress Syndrome). The purpose of this study is to research and evaluate the safety and efficacy of intravenous (IV) administration of bone marrow mesenchymal stem cell derived extracellular vesicles, ExoFlo, as treatment for Moderate-to-Severe ARDS. Bone Marrow Mesenchymal Stem Cell (bmMSC)-Derived Extracellular Vesicles is an investigational drug created from human bone marrow being studied for the treatment of moderate-to-severe ARDS. This is a research study that will involve monitoring oxygen and inflammation levels after taking the investigational product and assessing the safety of the investigational product. The experimental treatment is a biologic product called Bone Marrow Mesenchymal Stem Cell (bmMSC)-Derived Extracellular Vesicles Allograft Product ExoFlo, which is purified from the bone marrow of a healthy well-screened individual. Participants will receive either 15mL of the investigational product with 85 mL of normal saline or 100 mL of normal saline only (placebo). The expected duration of participation in the study is a maximum of 61 days, which includes 1-day screening prior to treatment and 60 days following the first treatment.

This study aims to improve the breastfeeding skills of premature or sick term infants with non-invasive, transcutaneous vagus nerve stimulation (taVNS). taVNS is microcurrent stimulation to the ear, which targets a vagus nerve branch. Pairing taVNS with motor activity, such as breast feeding, may help with motor learning in infants as it does in adults with stroke. Ten premature infants older than or equal to 35 weeks gestational age, or convalescing sick term infants whose mothers want to breastfeed will participate in this study with parental consent. Infants will receive 1 taVNS treatment paired with breastfeeding per day for up to 14 days. Before each treatment, the researcher will determine how much electrical stimulation is needed for the infant to feel a slight tingle without discomfort. This level of electrical stimulation will be delivered by a TENS unit (Transcutaneous elecrical nerve stimulation) and neonatal electrodes applied just in front of the ear and our custom made carbon electrode used in the BabyStrong studies (#10881, #67997). Stimulation will be timed with latching and sucking for the duration of the feed and will be on with sucking and off with rest. Pre- and post-feed weights, the length of time for each feed, and observations of latch, suck, and swallow efficiency will be recorded. Parental satisfaction will be assessed by questionnaires at the beginning, after 1 and 2 weeks, and 3 months after the end of treatment to assess infants' progress in and maintenance of breastfeeding abilities.
If pairing breastfeeding with taVNS is able to improve effective breastfeeding in infants in the neonatal intensive care units, it might help premature and sick term infants to successfully breastfeed at the time of discharge and maintain breast feeding at home after discharge. Premature infants may benefit from longer time receiving maternal breastmilk.

This phase I trial will determine the maximum tolerated dose of lenalidomide when given in combination with high-dose systemic methotrexate and rituximab, with or without nivolumab, as induction treatment of primary central nervous system lymphoma. In addition, whether the combination of drugs can extend the control of CNS lymphoma by being used as maintenance (prolonged treatment) after control is achieved with the initial chemotherapy regimen (induction) will be judged. If decided to take part in the study, participants will complete pre-study testing, and if allowed to participate in study different people will get different doses of the study drug lenalidomide during induction chemotherapy. If the drug does not cause serious side effects, the next group of people in the study will get a higher dose, and the doses will continue to increase for every new group until people have serious side effects that require the dose to be lower. Lenalidomide will be taken by mouth on days 5 to 14 of each induction cycle. Once the dose of lenalidomide is found, the next group of people in the study will receive nivolumab in combination with the other drugs (methotrexate, rituximab, and lenalidomide). The first drug administered in each cycle is rituximab, which is given as an intravenous infusion typically in the infusion center. The day after rituximab, participants will be admitted to the hospital for the infusion of methotrexate. Enrolled participants that present benefit after induction will receive lenalidomide and nivolumab as prolonged therapy (maintenance) for an additional 12 months (12 cycles and each cycle is 28 days) or until the disease gets worse or the side effects become too severe. After treatment is completed the study doctor will continue to follow up on participants condition for 2 years to observe side effects. After 2 years the doctor will continue to follow up either in clinic or by phone for up to 5 years after registration. The most common side effects known are kidney damage, infusion reaction, blood clots, birth defects, immune toxicity, fever and infections, and there may be some risks that the study doctor is not aware of yet. Once the combination is proven safe, this study will allow for future studies to determine whether the combination of these four drugs can improve the response to treatment and help increase the understanding of their use in primary CNS lymphoma treatment. It is unclear whether these drugs will help participants live longer than the usual approach alone.

This study is for patients with hypertrophic cardiomyopathy (HCM). HCM is a condition where the heart muscle becomes abnormally thickened, which can sometimes block the blood flow out of the heart and results in the heart muscle working harder to pump blood to the body. Participants who have completed participation in a previous HCM study investigating the study drug, called aficamten (CK-3773274), will be eligible to participate in this study.

The study is done to collect long-term safety and tolerability data, including assessments of cardiac structure and function during chronic dosing with aficamten. Aficamten is a tablet taken by mouth. This is an open label study (the participants and study team will know the dose of aficamten taken at any given time). If your screening results show you are eligible to continue in the study, you will visit the research site for the "first dosing day" (Day 1), followed by visits at Weeks 2, 4, 6, 12, then every 12 weeks thereafter. Study related procedures include blood work, echocardiograms (ultrasound test of the heart), electrocardiogram (recording of heart's electrical activity), physical exams, and questionnaires. Risks associated with this study include shortness of breath, nausea, diarrhea, headaches and dizziness.

This is a global, Phase 3b/4, randomized, open-label, efficacy assessor-blinded, multi-center study that will evaluate upadacitinib compared to dupilumab in adult subjects with moderate to severe AD and inadequate response to dupilumab after at least 6 months of current use. The study consists of a 35-day Screening Period; an 8-week randomized, open-label, efficacy assessor blinded treatment period for all participants (Period 1); a 24-week open-label, efficacy assessor-blinded extension period for all participants who finish Period 1 (Period 2) (total duration of Period 1 and Period 2 is 32 weeks); and a 30-day Follow-up visit.

In this study, researchers are testing a drug called Alisertib in people with a specific type of lung cancer that has spread extensively. These patients have already undergone the first round of treatment, but unfortunately, their cancer has started growing again. The drug alisertib works by targeting certain molecules involved in cell division, which are often overactive in cancer cells.

Patients will take alisertib as pills twice a day for a week, followed by a break. To manage side effects, they'll also receive another medication to support their blood cell production. Throughout the study, researchers will closely monitor how much alisertib is in the patients' blood and how they're responding to treatment.

The study will continue until patients either see their cancer progress, experience intolerable side effects, or decide to leave the study. Even if the cancer spreads to the brain during the study, patients might still be able to continue treatment if it's deemed helpful by their doctor. This research hopes to find out if alisertib can offer a new option for people whose lung cancer has come back after initial treatment.

The purpose of this medical research study is to evaluate the safety and effectiveness of a new medication called imatinib mesylate in the treatment of Lymphangioleiomyomatosis (LAM). LAM is a rare disease in which abnormal cells (called LAM cells) grow out of control. Over time, LAM cells destroy healthy lung tissue and cause respiratory disease or failure.

Many patients with LAM are currently treated with a medication called sirolimus (rapamycin). Sirolimus slows the growth of LAM cells.

Imatinib mesylate (hereafter called imatinib) is approved by the Food and Drug Administration (FDA) for the treatment of some cancers that share common pathways with LAM cells. Laboratory studies suggest that imatinib could completely block the growth of LAM cells through initiation of targeted cell death.

An important purpose of this research is to determine the safety of imatinib in people with LAM. This study will also evaluate the short-term effectiveness of imatinib. Participants will be randomized to receiving imatinib (study medication) or placebo (no treatment) for the 180 day duration of participation. The study is being conducted at the Medical University of South Carolina and at Columbia University in New York (CUMC). Each site will enroll 10 participants.

Each day in the United States, approximately 41 children experience in-hospital cardiac arrest (IHCA) requiring cardiopulmonary resuscitation (CPR). A lack of situation awareness was cited as the most common contributing factor to serious safety events within children's hospitals. Situation awareness is the ability to monitor what is happening, integrate information to develop a comprehensive picture, and extrapolate forward to project the future. The primary objective of this study is to implement unit based interventions (SAMURAI PICU bundle) to reduce the incidence of IHCA in pediatric intensive care units using quality improvement methodology.

This study is for subjects that have been diagnosed with mantle cell lymphoma. The purpose of this study is to compare continuous treatment with zanubrutinib to treatment with zanubrutinib that is stopped after the initial six 28-day cycles of chemotherapy and restarted at the first time your disease gets worse following the initial six 28-day cycles of chemotherapy. The subject may remain in the study for up to 10 years.