La Haye Pesnel, France

A Prospective Pivotal Study to Evaluate the Efficacy and Safety of Avastin® Bevacizumab (BEV) With or Without Microbubble-mediated Focused Ultrasound (FUS-MB) Using NaviFUS System in Recurrent Glioblastoma Multiforme Patients

The study aims to compare the efficacy of combining Bevacizumab with NaviFUS System relative to Bevacizumab alone in patients with rGBM who have previously undergone radiotherapy and temozolomide chemotherapy. Any patient with a histological diagnosis of GBM who meets all of the specific eligibility criteria may participate in this study by signing informed consent in person or through their legal representative. Eligible patients will undergo a 2-week baseline observation screening period. Up to 32 evaluable patients will be recruited in this study. Eligible patients will be randomized in a 1:1 ratio, with one group receiving the standard of care (SoC) BEV alone and the other group receiving treatment with microbubble-mediated FUS treatment in addition to BEV (FUS-MB+BEV). Eligible patients who assigned to the SoC group will follow the standard operating procedures of BEV (10 mg/kg intravenous (IV) infusion over 30-90 minutes). On the other hand, eligible patients assigned to treatment group will initially receive the same BEV schedule. After at least 30 minutes, patients will be administered microbubbles (MB) (SonoVue® ) at a dose of 0.1 mL/kg, along with optimal ultrasound exposure doses determined by the acoustic emission feedback FUS power control algorithm of the NaviFUS System. The treatment will be administered every 2 weeks up to 34 weeks or until evidence of progression disease (PD), intolerable toxicity precluding further treatment, non- compliance with study follow-up, or withdrawal of consent, whichever occurs first.

Development of Microbial Therapeutics for Metabolic-associated Fatty Liver Disease: From Mechanistic Investigations to Clinical Trials

Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD)is an improved diagnostic standard derived from Non-Alcoholic Fatty Liver Disease (NAFLD), emphasizing the correlation between fatty liver and metabolic dysfunction. Compared to NAFLD, which requires the exclusion of various conditions for diagnosis, the diagnostic criteria for MASLD can enhance the homogeneity of study subjects. It also addresses various groups with coexisting liver diseases, aiding in the efficiency and applicability of new drug development. MASLD has a prevalence rate of approximately one-fourth of the global population. If left untreated and worsens, it may lead to liver fibrosis, cirrhosis, or even liver cancer. Due to the significant medical burden associated with MASLD and the lack of FDA-approved treatments, the development of therapeutic methods for MASLD is an urgent issue. Past literature indicates that diet and gut microbiota play crucial roles in the progression of MASLD. The composition of the diet affects gut microbiota and intestinal barrier function. In cases of dysbiosis, harmful substances produced by gut microbiota, including pathogen-associated molecular patterns (PAMPs) and microbiota-dependent metabolites (MDMs), enter the liver through the portal vein via the leaky gut, resulting in toxicity. The pathogenic pathways exacerbating MASLD through gut microbiota dysbiosis, collectively termed the gut-liver axis, are not fully understood. Some animal studies have found dietary supplements to regulate gut microbiota beneficial for improving MASLD. Although most lack clinical evidence, incorporating food components that regulate gut microbiota and immune function into the diet indeed holds potential for treating MASLD. Next-generation probiotics have been found in past studies to improve liver lipid metabolism and regulate gut microbiota. They may slow the progression of MASLD by modulating the gut-liver axis. Previous studies by our team applied the pasteurized Akkermansia muciniphila strain NTUH_Amuc03 (pAKK NTUH_Amuc03), in preclinical animal studies to alleviate fatty liver disease progression. In experiments with mice induced with high-fat, high-fructose, high-cholesterol diets, pAKK NTUH_Amuc03 trended to reduce the body weight, improve abnormal blood lipids in mice, NASLD activity score, and HOMA-IR. These results indicate the potential of pAKK NTUH_Amuc03 to slow the progression of MASLD. Therefore, this project aims to further evaluate the efficacy and safety of pAKK NTUH_Amuc03 in MASLD patients through clinical trials.

Epigenetic Nucleosomes in Plasma for Pulmonary Nodule Differentiation

Currently, early lung cancer screening primarily relies on low-dose computed tomography (LDCT) of the chest. However, blood tests offer a more convenient alternative. Despite this, existing blood tests lack sufficient accuracy and sensitivity for lung cancer screening. Developing a reliable blood-based screening tool could significantly enhance the detection rate and accuracy of early lung cancer screening. Previous studies have shown that nucleosomes undergo variations during early cancer development. The Belgian company Volition has developed a blood test method based on chemiluminescence immunoassay (ChLIA) to measure nucleosomes in the blood, branded as Nu.Q™. Preliminary studies have demonstrated that Nu.Q™ can detect abnormal nucleosome biomarkers associated with early lung cancer. This study, in collaboration with Volition, will collect 20 mL of blood samples from individuals undergoing chest LDCT. Plasma will be isolated and analyzed using Nu.Q™ at the National Taiwan University Center for Genomics and Precision Medicine. The test results will be compared with corresponding lung cancer medical records, LDCT findings, and pathological diagnoses. The study aims to enroll 500 participants. The objectives of this study are to validate the diagnostic accuracy of the Nu.Q™ blood test for lung cancer in the Taiwanese population, compare its diagnostic performance with LDCT, and explore its potential role in lung cancer prevention and improved survival outcomes. This study is conducted as an industry-academic collaboration project with National Taiwan University.

The Effectiveness of Bu Zhong Yi Qi Tang in Patients with Myasthenia Gravis

:This study aims to assess the effectiveness of using a combination of traditional Chinese and Western medicine,to improve the meridian energy and autonomic nervous system function of myasthenia gravis patients.

Physiological and QoL Benefits of Qi-Gong in Post-acute Sequelae of Covid-19

Effect of Auricular Acupressure on Sleep Quality in Nurses

Background: Nursing staff face various pressures, shift systems, household responsibilities, and hormonal changes within the medical environment. They frequently experience issues such as sleep deprivation and inadequate rest, which can result in diminished work performance and increased fatigue. This, in turn, indirectly impacts the quality of care provided and heightens the risk to patient safety. Aim: Effect of Auricular Acupressure on Improving Sleep Quality in Nurses Methods: Adopting a quasi-experimental research design and convenience sampling, nursing staff from a northern medical center who scored 5 or higher on the Pittsburgh Sleep Quality Scale were selected as research subjects. Eligible participants were assigned to either the experimental group (auricular acupoint sticking) or the control group (no intervention). In the experimental group, the Shenmen point (MA-TF1) and Xin point (Xin MA) on both ears were treated with Wangbuliuxing seeds. Initially, the seeds were applied to the left ear for seven days, after which they were switched to the corresponding acupoints on the right ear. Following application, the seeds were pressed daily, once after each meal, with each acupoint being stimulated for 1 minute.Pittsburgh Sleep Quality Scale were measured on the day of application, as well as during the fourth and eighth weeks. The collected data were analyzed using SPSS 29.0 for Windows. Statistical analyses included percentages, means, chi-square tests, paired t-tests, independent t-tests, and generalized estimating equations to compare differences in sleep quality between the two groups.

Optimizing the Ocular Surface With Systane COMPLETE Pre- and Post-operatively in Patients With Dry Eye Planning for Cataract Surgery: An Extension Study of Optimizing the Ocular Surface With Systane COMPLETE in Patients With Dry Eye Planning for Cataract Surgery

STUDY OBJECTIVE： Compare the corneal astigmatism data before and after the use of Systane COMPLETE to evaluate its impact on predicting changes in postoperative residual astigmatism. Compare the effects of using or not using Systane COMPLETE on preoperative and postoperative Ocular Surface Disease Index (OSDI) scores and Non-Invasive Tear Break-Up Time (NITBUT). Background Cataract surgery is one of the most common and successful ophthalmic surgeries worldwide. However, cataract surgery can induce or exacerbate the severity of dry eye, leading to increased postoperative discomfort for patients. Additionally, undiagnosed preoperative dry eye can affect the accuracy of corneal astigmatism measurements, potentially impacting the astigmatic correction power of toric intraocular lenses used during surgery. While general moisturizing artificial tears have been shown to significantly reduce postoperative ocular discomfort and tear film instability, it is notable that up to 50% of patients undergoing refractive or cataract surgery exhibit abnormalities in the tear film lipid layer, meeting the diagnostic criteria for meibomian gland dysfunction (MGD). Given this, the application of lipid-containing nano-emulsion artificial tears before and after cataract surgery presents an unexplored opportunity to address two critical issues: reducing errors in corneal astigmatism measurements and alleviating dry eye symptoms induced by cataract surgery. This remains a topic worthy of investigation, as no existing studies have thoroughly examined these aspects. Methods This study is an extension of the "Optimizing the Ocular Surface with Systane COMPLETE in Patients with Dry Eye Planning for Cataract Surgery" trial (Research Ethics Committee Approval Number: 202311109MIPD), hereinafter referred to as the OOSSCC trial. The original OOSSCC trial began recruitment in May 2024 and focuses on analyzing patients with dry eye symptoms scheduled for cataract surgery. The trial evaluates the changes in corneal anterior surface astigmatism measurements, Ocular Surface Disease Index (OSDI) scores, and Non-Invasive Tear Break-Up Time (NITBUT) before and after one month of preoperative treatment with Systane COMPLETE.This trial will extend the study period to one month post-surgery and will be divided into two parts: Experimental group: This part extends the use of Systane COMPLETE for participants in the original OOSSCC trial to one month post-surgery. The aim is to compare corneal data before and after using the trial drug to determine which time point provides more accurate predictions of postoperative residual astigmatism. The anticipated results may serve as a reference for preoperative management to reduce corneal astigmatism prediction errors in cataract surgery patients with an OSDI score greater than 12. Additionally, this study aims to assess differences in corneal astigmatism prediction accuracy among patients with varying NITBUT levels. control group: This part involves recruiting additional cataract patients who meet the same age and dry eye inclusion criteria as the original OOSSCC trial group to serve as a control group. It will compare the effects of using Systane COMPLETE on preoperative dry eye symptoms and postoperative dry eye symptoms. The anticipated results may provide recommendations for managing postoperative dry eye symptoms in cataract surgery patients with an OSDI score greater than 12. Anticipated Results It is expected that for cataract patients with preoperative dry eye symptoms, particularly those with meibomian gland dysfunction, the study will improve the effectiveness of postoperative astigmatism correction while reducing discomfort caused by dry eye symptoms after surgery. Hypothesis： Viscous artificial tears have been proven to alter preoperative corneal measurements in patients planning to undergo cataract surgery. This study aims to analyze the impact of lipid-containing nano-emulsion artificial tears on predicting residual astigmatism after cataract surgery. mpact on Meibomian Gland Dysfunction and Dry Eye Symptoms:Meibomian gland dysfunction is the most common cause of evaporative dry eye. Cataract surgery alters the structure and function of the meibomian glands and reduces the thickness of the tear film lipid layer. However, no studies have yet reported the effectiveness of this type of artificial tear in alleviating dry eye symptoms induced by cataract surgery. Objectives： Compare the corneal astigmatism data before and after the use of Systane COMPLETE to evaluate its impact on predicting changes in postoperative residual astigmatism. Compare the effects of using or not using Systane COMPLETE on preoperative and postoperative Ocular Surface Disease Index (OSDI) scores and Non-Invasive Tear Break-Up Time (NITBUT). Inclusion Criteria (experimental group) Cataract patients who participated in the "Optimizing the Ocular Surface with Systane COMPLETE in Patients with Dry Eye Planning for Cataract Surgery" trial (Research Ethics Committee Approval Number: 202311109MIPD) and did not withdraw from the trial midway. Exclusion Criteria (experimental group) Patients unwilling to participate in this trial after surgery. Inclusion Criteria (control group) Cataract patients aged between 20 and 85 years. Patients with normal cognitive function who are able to complete the dry eye questionnaire (with responses recorded by the research team) and are willing to undergo phacoemulsification and intraocular lens implantation under topical anesthesia. Exclusion Criteria (control group) Unable to answer the questions in the dry eye survey. Ocular trauma or ocular surgery in the planned surgical eye, active ocular infection, and obvious abnormalities in ocular surface or eyelid margins other than MGD cause decreased visual acuity other than cataracts. Dry eye signs: Corneal Fluorescein Staining CFS (+) to exclude any corneal abnormalities or epithelial defect. Systemic drug use, including tetracycline derivatives, antihistamines, and isotretinoin. Using dry eye medication at screening stage. Sample Size This study plans to enroll a total of 140 participants, with 70 participants in the trial group and 70 in the control group.

A Study of Using the Stoma Self-care Apps by Patients With Enterostomy

Background: Self-care for patients after enterostomy surgery includes both cognitive and skill aspects. Insufficient self-care ability, inability to tell self-care precautions, and incorrect steps in performing care skills lead to leakage of the ostomy bag, and 70% of peristomal skin lesions occur. Complications lead to increased hospitalization days, readmission rates, and medical costs. Pain and other discomforts caused by skin complications around the stoma can cause anxiety, depression or anger, followed by financial burdens and impacts on families, affecting the quality of life. Ostomates use paper texts and oral instructions to provide post-enterostomy nursing care instructions. There is no regular follow-up mechanism after discharge. After returning home, enterostomy patients' self-care ability and adaptability to the stoma will be tested. Changes in the defecation outlet after enterostomy surgery affect many aspects. Patients need to relearn daily care. Physically, they need to maintain the cleanliness of the ostomy bag collection system at all times. Their lifestyle must be consistent with postoperative diet and exercise. Changes; psychologically, the changes in body function and appearance, anxiety, depression, or anger caused in the process of adapting to the enterostomy lifestyle, followed by the financial burden and impact on the family, and the physical, mental, and spiritual impact of family members on each other. It is a huge change, providing ongoing care guidance and support to ensure self-care and quality of life after returning home, meeting the constraints faced by patients with enterostomy needs and the challenges faced by their care guidance. Purpose: This study uses a stoma self-care app, accessed through LINE official account, a communication software commonly used by Chinese people, as an intervention measure to integrate technology acceptance and task technology adaptation models to explore the correlation of each aspect and its impact on self-care ability and quality of life. Whether the factors and task technology adaptability will affect the willingness and usage behavior of enterostomy patients, the research subjects can effectively improve their self-care ability, quality of life, usage willingness, and usage behavior after intervention. Method: It is a quantitative, single-blind, simple randomly assigned, quasi-experimental study. The surgical ward and stoma treatment room of a medical center in northern Taiwan accepted patients with enterostomy, including 25 patients in the control group and 25 patients in the experimental group. The interventional measures were performed on the first day after enterostomy surgery, using integrated technology to receive and adapt task technology. Model, the enterostomy self-care knowledge scale, and the stoma self-care ability scale (UES) are used to evaluate self-care ability, and the stoma patient quality of life scale (Stoma-QOL) is used to evaluate the quality of life, and a questionnaire survey is conducted. Analyze task technology fit.

Multi-omics Study in Citrin Deficiency

Citrin deficiency (CD) is an inherited autosomal recessive metabolic condition that is also a secondary urea cycle disorder caused by mutations in the SLC25A13 gene, which encodes for the mitochondrial transporter, citrin. Citrin is a key component of the mitochondrial malate-aspartate shuttle (MAS) and is responsible for moving Nicotinamide Adenine Dinucleotide (NADH) from the cytosol into the mitochondria via reducing equivalents such as malate, which drives mitochondrial respiration to produce energy in the form of adenosine triphosphate (ATP). The MAS is also critical in regulating Nicotinamide Adenine Dinucleotide (NAD+/NADH) redox balance to maintain cytosolic redox-dependent metabolic pathways such as glycolysis, gluconeogenesis, amino acid metabolism, and lipid metabolism. Citrin is also required to supply cytosolic aspartate, which is the substrate of one of the urea cycle enzymes, namely argininosuccinate synthetase 1, and thus important for the proper functioning of the urea cycle. The clinical presentations of citrin deficiency often vary widely between patients but can generally be distinguished by distinct clinical phenotypes, which are neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) that affects infants, the "failure to thrive and dyslipidemia" form of CD (FTTDCD) in childhood, the adaptation or silent period, and citrullinemia type II (CTLN2), which represents the most severe form of the condition. While only a small percentage of CD patients develop CTLN2, the prognosis for these patients is typically poor. It is notable that all CD patients above 1 year old (post-NICCD) naturally develop a characteristic food preference that favors a diet rich in protein and fat while being low in carbohydrates. Other clinical findings observed in some CD patients include fatty liver, fatigue, hypoglycemia, and failure to thrive. There is currently no effective cure for CD. Before the onset of CTLN2, patients are primarily managed by diet control with a low carbohydrate, high protein and high-fat diet, as well as medium chain triglyceride (MCT) supplementation. CTLN2 patients have been treated with sodium pyruvate, arginine, and MCT with limited success, with severe cases requiring liver transplantation as the only solution. There are currently no specific biomarkers that effectively track the disease progression, making it challenging to monitor how well patients are actually doing or to measure the effectiveness of therapies. Without proper management or timely medical interventions, patients may develop CTLN2. Given the urgent and unmet need for biomarkers specific to CD, the main goal of this study is to uncover disease-specific biomarkers by analyzing blood samples collected from CD patients using both targeted and untargeted metabolomics, proteomics, lipidomics, and transcriptomics. Targeted omics will involve the analysis of cellular pathways associated with the condition, such as the MAS pathway, glycolysis, protein metabolism, de novo lipogenesis, lipolysis, gluconeogenesis, NAD+ metabolism, ureagenesis, and the glutamine synthetase pathway. Identification of such biomarkers will allow a deeper understanding of the disease pathogenesis. Importantly, these biomarkers may enable better tracking of disease progression and may help to prevent the onset of CTLN2. Finally, these biomarkers will also greatly benefit the development of effective therapeutic options for CD in clinical trials by serving as measurable endpoints. Obtaining the necessary material from patients consists of a minimally invasive venous blood sampling taken during a regular outpatient visit and after the informed consent of the patients or caretakers.

Digital Sleep Program for College Students with Insomnia

This is a parallel-group, randomized controlled trial (RCT). 90 participants who experiencing insomnia for at least 3 months with college students will be enrolled. Eligible participants who complete the baseline measurements will be randomly allocated to a digital-based multimodal sleep management program group (N = 45) and a waitlist control group (N = 45). The primary outcome is insomnia severity, assessed using the Insomnia Severity Index (ISI). The secondary outcomes include daytime sleepiness, objective sleep parameters, sleep reactivity, resilience, anxiety, and depression, which will be examined using the Epworth Sleepiness Scale (ESS), a wearable sleep tracker, the Ford Insomnia Response to Stress Test (FIRST), the Brief Resilience Scale (BRS), the State-Trait Anxiety Inventory (STAI), and the Beck Depression Index II (BDI-II), respectively. Additionally, chronotype will be assessed using the Morningness-Eveningness Questionnaire (MEQ) as a moderating role to be tested in this study. All outcomes will be measured at three time points: T0 (baseline assessment), T1 (immediately after the 4-week intervention period), and T2 (4 weeks after the intervention period).