Postoloprty, Czech Republic

tES Modalities for the Treatment of ADHD

This project aims to evaluate the therapeutic potential of transcranial electrical stimulation (tES) modalities, specifically transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), as innovative, non-invasive interventions for managing Attention-Deficit/Hyperactivity Disorder (ADHD) in children and adolescents. ADHD is a neurodevelopmental disorder characterized by persistent inattention, hyperactivity, and impulsivity that impair daily functioning. Conventional treatments, such as pharmacological interventions and behavioral therapies, may have limitations, including side effects or variable efficacy, prompting the exploration of neuromodulation techniques like tES.

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.

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.

Coated or Chewable Aspirin and a Hybrid Strategy to Mitigate Adverse Effects of Air Pollution in Stable Atherosclerotic Disease

- Background: Aspirin is a key treatment option of patients with atherosclerotic cardiovascular disease (ASCVD). The enteric coating has emerged as a potential solution to minimize the exposure of the gastric mucosa to the medication. However, change in the medication main site of absorption might negatively impact the pharmacokinetics/pharmacodynamics of aspirin and alter its antithrombotic properties, leading to diminished efficacy of the medication. A sufficiently large randomized controlled trial with a long-term follow-up to compare the effectiveness of enteric-coated versus plain aspirin in reducing adverse cardiovascular events and mitigating the adverse effects of the medication in patients with ASCVD is lacking. Ambient air pollution is a prominent cause of mortality, being associated with 6.7 million deaths worldwide every year, half of which are attributable to cardiovascular causes. Near the half of these deaths is attributable to cardiovascular causes. Several patient-level interventions have been proposed to counteract with the adverse effects of the air pollution, including alerting patients via text message, staying at home, using face masks, or consuming citrus fruits (as a source of vitamin C) during the days with air pollution. However, the effect of implementing these strategies, individually and especially as a group, in mitigating the adverse effects of the air pollution has not yet been studied in a randomized controlled trial powered for clinical outcomes. The purpose of the current randomized clinical trial is to compare the efficacy and safety of enteric-coated versus plain low-dose (81 mg) aspirin formulations in a double-blind fashion, and an open-label comparison of a multifaceted intervention including a one-page informational flashcard, cell phone message alerting on days with poor air quality to encourage patients not to spend time outdoors or to wear KN-95 facemasks outdoors in those days, and encouraging patients to consume citrus fruits on highly polluted days (hereafter referred to as hybrid strategy), versus usual care, in a multicenter randomized controlled trial (RCT) with a 2x2 factorial design. - Design and Randomization method: Multicenter randomized controlled trial with a 2x2 full factorial design with double-blind randomization with a 1:1 allocation ratio to low-dose enteric-coated vs plain aspirin, and open-label randomization with 1:1 allocation ratio to hybrid strategy to reduce the cardiovascular effects of air pollution vs usual care. Permuted block randomization with block sizes of 8, 12 and 16 chosen randomly via an electronic web-based system will be used for the study. The allocation sequence will be concealed. All outcomes will be adjudicated by a Clinical Events Committee blinded to the assigned treatments. - Setting: Teaching hospitals in Tehran province, Iran will be involved. - Statistical consideration and sample size calculation: An event-driven approach was considered for the calculation of sample size. Considering a relative hazard reduction of 23% in the first (aspirin formulation) randomization and 25% in the second (air pollution mitigation strategy) randomization, to provide a two-sided alpha of 0.05 and a statistical power of 80%, a total number of 460 primary efficacy outcomes for the first randomization and 380 primary efficacy outcomes for the second randomization would be needed. An event-rate of 18.5% for the incidence of primary efficacy outcome in the control arm of the first randomization, and 19.2% for the incidence of primary efficacy outcome in the control arm of the second randomization was assumed per a median follow-up of 2-year. Ultimately, Considering 4% dropout rate per each randomization, a total number of 2920 and 2732 patients would be needed for the first and second randomizations, respectively.

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.

Evaluating the Efficacy of "Digestive Aid" in Functional Dyspepsia

This double blind placebo-control clinical trial is performed in dyspeptic patients referred to the gastroenterology clinic in Sina Hospital. Neither the participants nor the researcher knows which treatment or intervention are provided until the end of trial. The new onset dyspeptic patients that are older than 18 years of age will be included in the project. The gastroenterologist diagnose FD after taking the complete medical history, physical examination, laboratory investigations and performing upper gastrointestinal endoscopy. Participants with co-morbidities (known GI diseases), taking medications, those with abnormal gastrointestinal findings in physical examination and para-clinical investigations will be excluded from the research. FD will be diagnosed based on the Rome 4 criteria. Participants will fill out an informed written consent prior to the enrollment. The trial has two arms. The patients in case group receive the film-coated "Digestive Aid" product once daily for 2 months. The control group takes the placebo for the same duration. Both products are manufactured by Darman Yab Darou Incorporation, Tehran, Iran. The caregiver who gives the medication to the participants is blind to the type of capsules. Block Randomization will be used to assign the participants to intervention or placebo group considering their age and gender. The efficacy of medication on the severity of symptom is evaluated by the valid Persian version of the "Leeds dyspepsia questionnaire" (LDQ).(3) This questionnaire evaluates 8 dyspeptic complaints. Epigastric pain, retrosternal pain, regurgitation, nausea, vomiting, belching, dysphagia, and early satiety are the key elements that are evaluated in this questionnaire. The severity of symptoms are graded from 0 to 8. The sum of scores in all 8 items of the questionnaire represents the patients' total score. The Primary outcome measure is defining the changes of dyspeptic symptoms from baseline to the end of treatment. A statistical power analysis is used to calculate the sample size. Considering the two-sided significant level (α) of 0.05 and the power of 90% (β = 0.1), a total sample size of 46 patients is determined to detect one percent inter-group difference in LDQ score. (For detailed information, please refer to http://hedwig.mgh.harvard.edu/sample_size/js/js_parallel_quant.html). To allow for a 5% possible dropout rate, 50 patients will be recruited in the trial. Analysis of covariance (ANCOVA) will be applied for comparing treatment groups regarding the changes of variables during the study. All statistical analyses will be performed using SPSS version 17 (SPSS, Chicago, IL, The USA). The probability of the difference between the dependent and independent variables is considered significant if a two-tailed P value is less than 0.05.

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

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.