Tehran & Zanjan, Iran, Islamic Republic of

Comparing High-protein Vs. Standard Protein Nutritional Support in Critically Ill Patients At Risk for Refeeding Syndrome

Patients will be randomly assigned to two groups: the high-protein group and the standard-protein group. Upon ICU admission, and after meeting the inclusion criteria and identifying a risk of refeeding syndrome (RS), they will be allocated to one of the two groups. Patient selection for RS risk will be based on the diagnostic criteria outlined in the 2020 ASPEN guidelines. The m-NUTRIC and APACHE II scores will be calculated for all patients at ICU admission and 24 hours before the initiation of feeding. Monitoring for multi-organ dysfunction syndrome (MODS) will involve daily laboratory tests and organ failure assessment using the SOFA score. Before starting the nutritional intervention, all patients will receive 100 mg of thiamine daily for one week, along with a daily multivitamin-mineral supplement. Due to the risk of RS, calorie intake will begin at low levels and will be cautiously increased in both groups. To calculate the energy needs, ideal body weight will be used. In the high-protein group, the target protein intake will be 2 grams per kilogram of body weight per day, while in the standard-protein group, it will be 1.3 grams per kilogram of body weight per day. Protein will be introduced gradually, starting from a low level, as part of nutritional support, with whey protein powder added if needed as a supplement. If serum creatinine levels rise, protein powder will be removed from the patient's diet. The intervention duration will be 14 days, with a minimum of 5 days. The primary clinical outcome is the incidence of refeeding syndrome (RS), while secondary outcomes include the occurrence of infections, hospital length of stay, ICU length of stay, multi-organ failure, and mortality within 45 days of admission. RS will be diagnosed according to the 2020 ASPEN guidelines. Serum concentrations of potassium, magnesium, phosphate, glucose, urea, and creatinine will be measured daily for one week.

40 Hz Transcranial Alternating Current Stimulation for Inducing Gamma Oscillations

Safety and Efficacy of Systemic Allogenic NK Cells in R/R Neuroblastoma

NK cells are isolated from healthy donors through the apheresis process and subsequently separated using the CLINIMACS device in a clean room environment. After quality assessment (sterility, viable cell count, purity, and phenotype of active cells), they are stored at -198°C until use. Upon need, the cells are thawed and washed, followed by checking their viability, count, and sterility. Children between the ages of 2 to 16 who meet the eligibility criteria will be added to the study. After admission, the cells are injected into the patient at a ratio of 5×10^6 cells per kilogram of the patient's body weight. A total of 3 injections are administered to all patients. Based on the patient's response and recovery status, the need for additional injections is evaluated. If improvements in the patient's condition are observed after the last injection and confirmed by MRI MIBG, further 2 injections can continue. The intervals between injections vary based on the patient's standard treatment, and the cells are injected 10 days after the completion of each chemotherapy course.

Injection of Active Allogeneic Natural Killer Cells in Patients With Gliomas

Inclusion criteria: New diagnosed patients with grade 3 or 4 brain tumor, based on WHO classification, which are included in the one of the following conditions: • Astrocytoma, IDHmutant • Oligodendroglioma, IDH-mutant • Glioblastoma, IDH-wild type • Diffuse midline glioma • Diffuse hemispheric glioma • Diffuse pediatric-type high-grade glioma, IDH-wild type Age range of 3 to 60 years old both sex Lansky/Karnofsky performance score above 60 Obtained informed consent of patients or parents or legal attendance in cases of pediatrics Hemoglobin above 10 gr/dL of blood Absolute granulocyte count (AGC) above 500 per microliter of blood Platelet count above 50000 per microliter of blood INR below 2 and PTT less than 1.5 times of maximum normal value Plasma bilirubin level less than 1.5 times of maximum normal value Plasma hepatic transaminases (ALT and AST) level less than 3 times of maximum normal value Plasma creatinine level less than 1.5 times of maximum normal value Exclusion criteria: Evidence of radio necrosis in MRI or MRS Intolerance of new treatment due to emergency condition History of other malignancies History of any immunodeficiency diseases or any immune compromising conditions Rupture of cerebral shunt or unable to perform a lumbar puncture Pregnancy History of uncontrolled chronic diseases such as: Diabetes, CHF, liver cirrhosis, CKD, etc

Limbal Stem Cell Derived Exosome (LSC-Exo) Eye Drop for Treatment of Dry Eye

Dry eye is among the most prevalent chronic conditions in ophthalmology, significantly impacting quality of life and presenting a public health challenge that cannot be overlooked. Current treatment options primarily consist of artificial tear replacement, anti-inflammatory therapies, and local immunosuppressive treatments, which mainly focus on alleviating discomfort and other symptoms associated with the ocular surface. However, with the rapid advancements in regenerative medicine, ophthalmologists are exploring innovative approaches to treat dry eye. Chronic dry eye can result in corneal damage and potential vision loss. Recent studies suggest that therapeutic exosomes delivered as eye drops can enhance the immune microenvironment of the cornea and alter the ocular surface's microenvironment for better outcomes. Exosomes are membrane vesicles secreted by parental cells, which can mediate the transfer of RNA, protein, DNA and other functional molecules of the parent cell between other cells and regulate the function of target cells. The therapeutic potential of Limbal Stem Cell Exosomes has been studied by our department. We found that LSC-Exo can alleviate the symptoms of dry eye in the animal study. At present, we plan to clarify its efficacy in a clinical research. The main objective of this study is to evaluate the alleviation of Dry Eye symptoms in patients which are resist to conventional treatment by tear drops. The assessment will be done after LSC-Exo treatment by measuring Ocular Surface Index Score (OSDI), and the second objective include the measurement of inflammatory and pro-inflammatory cytokines in tear of patients, tear secretion amount, tear break time, the areas stained by fluorescent, ocular redness, tear meniscus and best corrected visual acuity. Approximately 30 patients will be recruited. The treatment group will receive artificial tears for 2 weeks to normalize the baseline, followed by intervention of LSC-Exo 10ug/drop, four times a day for 30 days. The follow-up visit will be 12-weeks and the progression of dry eye will be measured.

SCAD : a Registry of Spontaneous Coronary Artery Dissection

Observational, multicentre, international retrospective and prospective cohort study. Since this is an observational study, a formal sample size is not necessary. At least 500 prospectively recruited patients and 500 historical cases will be enrolled. Patient data will be collected at the following time-points: - First SCAD event visit (retrospectively on chart review) - First follow-up: at time of enrolment - Yearly follow-up: up to 1, 2, 3, 4 and 5 years post enrolment or until study completion Approximately 30 countries and 120 sites will participate in this registry.

Safety and Efficacy of CAR T Cell Therapy in Patients with R/r B-ALL

B-cell acute lymphoblastic leukemia (B-ALL), as the most common type of pediatric tumor, is identified by unregulated cell proliferation of immature lymphoid cells that can infiltrate the bone marrow and blood. Also, relapse and refractory B-ALL (R/R B-ALL) is the main reason of global mortality due to the constraints of combination chemotherapy. Over the past few years, substantial advancements have been made in treatment of ALL, specifically in the R/R context. Chimeric antigen receptor T (CAR-T) cells are a type of cancer immunotherapy treatment that function through modification of patient T cells to express CAR antigen on their surface. CAR-T cells aimed at CD19 have demonstrated promising activity in treatment of r/r B-ALL. In this study we aim to evaluate safety and efficacy of Anti-CD19 CAR T cell therapy in children with R/R B-ALL.

Comparison of Intralipid With SMOF Lipid Following HSCT

Patients will be randomly divided into two groups: the intervention group (TPN based on SMOFLipid) and the control group (TPN based on IntraLipid). At baseline (before HSCT) and after obtaining informed consent and assent, blood samples will be collected to test for biochemical markers, including total cholesterol, TG, LDL, HDL, FBS, Alb, Na, K, Ph, Ca, Mg, CRP, IL-6, BUN, Cr, and CBC. Furthermore, data on nutritional intake (total energy and protein) and appetite status will be gathered. The primary outcomes are neutrophil and platelet engraftment, defined as >500 for neutrophils and >20,000 for platelets, respectively. The possibility of oral intake, as well as the achievement of oral + ONS and total oral nutrition alongside TPN duration, will be recorded. On days +15 and +30, biochemical and anthropometric markers will be collected again. Furthermore, clinical outcomes such as acute GVHD, cholestasis, bleeding, infections, hospitalization, and mortality will be reported.

Naringenin Supplementation in Bone Fracture Patients

The study subjects will be selected from among the patients with bone fractures of the lower limbs who are hospitalized in the orthopedic department of Ayatollah Taleghani University Hospital in Tehran. The following criteria will be used to determine which patients are eligible for inclusion in the study: Inclusion criteria: patients aged 18 to 60 years, candidates for orthopedic surgery for bone fractures of the lower limbs, ambulatory without assistance for a minimum of two months prior to the fracture, not having undergone amputation of the lower limbs, not suffering from liver cirrhosis, not suffering from advanced kidney failure (blood creatinine higher than 1.4 mg/dL), not having metastatic cancer. Additionally, subjects must not have any chronic inflammatory diseases, nor must they be taking any drugs that affect bone metabolism, including calcitonin, bisphosphonates, and corticosteroids. Furthermore, subjects must not be taking any anti-inflammatory drugs. Subjects will be excluded from the study if they experience an allergic or intolerant reaction to Narangenin capsules, if there are any abnormal changes in their liver, kidneys tests, or if they fail to consume more than 10% of their capsules in weekly monitoring. Subjects will be randomly assigned to one of two intervention groups (Narangenin capsules) or a control group receiving a placebo. Patient assignment will be conducted using the stratified permuted block randomization method. Patients will be randomly assigned to one of two intervention groups (narangenin capsules) or a control group (placebo) based on their history of diabetes. Each stratum will consist of four cases, with two cases assigned to the placebo group and two cases assigned to the naringenin group. To ensure the blinding of the study, the capsules will be identical in appearance and packaged in the same containers. Each capsule of the intervention group will contain 250 mg of naringenin, while each capsule of the control group will contain 250 mg of starch. The capsules are administered to the patients by the nursing staff, who are unaware of the patient grouping. The supplementation regimen will commence one day following surgery, with participating patients receiving two capsules (equivalent to 500 mg) daily for 14 days. Subsequently, following a 14-day period, the patients will resume the maintenance dose of 250 mg per day until the 90th day post-surgery. During the intervention period, patients will be monitored for regular use of the capsules and any adverse reactions. Patients will be required to attend the hospital's orthopedic clinic on two occasions: 14 days after surgery and three months after surgery. During these visits, fasting blood samples will be taken for biochemical tests. The fusion status of patients will be evaluated by radiography after surgery, 14 days, and three months after surgery. Additionally, functional testing (Oswestry disability index (ODI)) will be performed two weeks and three months after surgery.

DEBIRI Plus Chemotherapy vs. Chemotherapy Alone in Colorectal Cancer Liver Metastases

Upon acquiring ethical approval, patients with histologically proven, unresectable or borderline resectable liver metastases from colorectal origin who are referred to the hepatobiliary clinic between September 2024 and September 2026 will be enrolled to the study. Informed consent will be obtained for their participation prior to enrollment. A total of 116 patients who are chemotherapy-naïve for their metastatic disease, will be randomly assigned to either the treatment group or the control group. With the aim of controlling major confounding factors, Stratified randomization will be performed based on synchronous/metachronous liver metastases and unresectable/borderline resectable status. Targeted therapy administration for each treatment group in based on oncologist's decision and will be tailored to the tumor's biological characteristics and the patient's clinical status. Ultimately, patients will be categorized into one of the two following treatment groups: Group 1: DEBIRI+ standard systemic chemotherapy ± Targeted therapy Group 2: Standard systemic chemotherapy ± Targeted therapy The Tumor characteristics, including the number, size, and anatomical location, as well as the presence or absence of extrahepatic metastases, will be assessed based on initial imaging (MRI). The treatment protocol is defined as the administration of a chemotherapy regimen on days 0 and 14, followed by DEBIRI on days 7 and 21. Each patient of the treatment arm will receive at least two doses of DEBIRI unless treatment-limiting adverse events occur. After 4 cycles of chemotherapy and 2 cycles of DEBIRI, patient reassessment to evaluate treatment response will be performed using MRI or CT scan within 1-3 months of treatment initiation. All imagings will be reviewed by 2 radiologists who are blinded to clinical information regarding treatment arm. Treatment response will be determined using RECIST criteria. Conversion to resectability, as primary endpoint, will be evaluated at a three-month follow-up multidisciplinary team (MDT) meeting, guided by established clinical guidelines. Secondary endpoints of the study will encompass evaluation of treatment tolerability and adverse event rate, alongside analyzing progression-free survival and overall survival.