Metabolic Disorder

In Thıs study, we aım to evaluate the erectile status of male patients undergoing percutaneous coronary intervention after both heart attack ( group 1) and stable angina ( Group 2). The primary aim is to assess any possible predictive effect of erectile function status on cardiac events. The secondary aim is to assess the direct effect of myocardial infarction on ED status by comparing the two groups. The secondary objective is to assess and analyse other determinants in the natural history survey of erectile status after the intervention. All male patients who undergo a successful PCI and survive will be evaluated. Patients who have had: Malignancy, underlying neurological diagnosis interfering with erectile status, uncontrolled diabetes, and more than two chronic medical conditions, on polifarmacy ( more than three medications a day), and no sexual relationship, who have not agreed to include the study, will not be included in the study. The follow-up period will be 0 (the time the patient recovered well after the intervention). Questinnaiere will examine the status over the last 3 months. 3 and 6-month follow-up. During the follow-up period, the interviews will be conducted face-to-face in the clinical environment, either by a responsible doctor or an educated nurse. The surveys include: IIEF (International Index of erectile function ) questionnaires BECK depression inventory questionnaires FCRP ( Fear of Cardiac Recurrence and Progression Scale ) The objective scale we use: Age SYNTAX score and residual SYNTAX score for evaluating the cardiac vessels occlusion status Cardiac Ejection Fraction status Laboratory values, including testosterone levels, Bodily measurements, including body mass index and waist circumference. Medications Medical conditions Intervention route ( trans radial or femoral ) The survey will take place in our institutions. The hypothesis is that erectile dysfunction is a preliminary condition of an upcoming cardiac event. Myocardial infarction causes significant changes in erectile function in a natural survey. The syntax score has a direct correlation with the baseline erectile function Residual syntax score has a direct relation with post-intervention erectile status.

Traditional Chinese Medicine (TCM), one of the intriguing features of traditional Chinese culture, has a history of more than 2,000 years, with both unique theories and rich experience. Because of the lack of objective and quantitative evaluation criteria, TCM is complementary or alternative medicine in most Western countries. However, in China, more than 71.2% of patients who have experienced Western medicine, TCM, and integrative medicine (both Western medicine and TCM) preferred the integrative approach, and 18.7% chose TCM as their favourite. Moreover, TCM is increasingly welcomed in many developed countries, such as Australia and the United States. Importantly, patients who used more types of TCM tended to use much less Western medicine recommended by current guidelines. Recent review also highlighted the potential use of TCM as a complementary and alternative approach to the primary and secondary prevention of cardiovascular disease. Perfect Heartio (PH) is a nutritional drink composed of mainly diluted herbal extracts of TCM, including ginger, Glycyrrhiza uralensis, Alternanthera sessilis, Panax notoginseng, red date, Codonopsis pilosula, Ligusticum chuanxiong, Astragalus membranaceus. Broad pharmacological properties of ginger and its bioactive components have been reported, suggesting its potential use in preventing CVD. Glycyrrhiza uralensis stands out for its exceptional therapeutic potential, particularly in enhancing cardiac muscle regeneration, and slowing muscle aging. Alternanthera sessilis has been showed to prevent cardiovascular and liver diseases. Panax notoginseng improve angiogenesis. Red date exerts anti-adipogenicity effects and enhancing endothelial function. Codonopsis pilosula improves the functional state of the cardiovascular system and mitigating the onset and progression of CVD. Ligusticum chuanxiong has been showed to promote blood circulation and remove blood stasis. Astragalus membranaceus also showed to improve cardiovascular function, protect myocardial cells, and increase coronary blood flow.

* Primary objective: * To describe the clinical presentation and outcome of genetically defined cases of pediatric hepatic glycogen storage diseases (GSD) patients. * Study population: Genetically confirmed cases of hepatic GSDs will be enrolled from all the participating centres. * Study design: Multicentric retrospective study (with concomitant long term prospective data collection) * Study period: The study will be an ongoing effort with aim to continuosly expand the participation. Retrospective data collection (of previous data), analysis and drafting of manuscript would be completed between May 2024 to April 2025. New centers willing to join the consortium will be asked to submit their data as on the date of joining. Retrospective follow up data may be asked from the participating centres every every 6 months-1 year. Also, we would continue prospective data collection of newer GSD patients at the collaborating centres.

During the two-month-long baseline lead-in phase, we will acquire the following information, which are part of standard clinical care: 1. Medical history 2. Pregnancy test for subjects of childbearing potential: using a urine human chorionic gonadotropin test 3. Number of hospitalizations in the last 12 months 4. Physical examination 5. 6-minute-walk test 6. Clinical laboratory biomarkers completed and/or interpreted at the CLIA-certified labs at Children's National Hospital: * GDF-15 * FGF-21 * CMP * Hemoglobin A1C * Plasma amino acids * Lactate * Carnitine and acylcarnitine * Urine organic acids and urine analysis 7. Standard 1 hour-long EEG for MELAS subjects 8. Baseline MRI (for subjects with MELAS or LHON-Plus) and MRS (for MELAS subjects) 9. Screen for stroke-like episodes for MELAS subjects 10. Electronic seizure diary for MELAS subjects 11. Motor examination for subjects with MELAS or LHON-Plus 12. Electromyography and nerve conduction velocity for LHON-Plus subjects 13. Ophthalmological examination (fundi, visual field, and visual acuity) for LHON-Plus subjects 14. Snellen chart exam for LHON-Plus subjects 15. Lumbar puncture for LHON-Plus subjects to assess CSF markers for multiple sclerosis-like: * A specific group of antibodies referred to as oligoclonal bands * Myelin basic proteins (MBP) * IgG levels * Levels of inflammasome proteins * Leukocytes count: lymphocytes (B-cells and T-cells), monocytes, macrophages, plasma cells, and granulocytes * CSF/serum glucose ratio 16. Fatigue screen using the Modified Fatigue Impact Scale 17. Quality of Life (QoL) is assessed using the short questionnaire "Neuro-Quality of life" 18. Cognitive assessment using the NIH-Toolbox Cognitive Battery 19. Skin biopsy to assess: * Mitochondrial Genetic Analysis: Quantification of the heteroplasmic levels of MELAS and LHON-Plus mitochondrial variants by long-range PCR followed by massively parallel sequencing done at Baylor Miraca Genetics Laboratories DBA Baylor Genetics, Clinical Diagnostics Laboratory. * Mitochondrial Respiratory Chain Enzyme Analysis: Quantification of enzymatic activity of oxidative phosphorylation (OXPHOS) Complexes by spectrophotometry done by Baylor Genetics. * Mitochondrial Fitness Assays: The mitochondrial fitness of participant-derived dermal fibroblasts are assessed in real-time by live-cell mitochondrial assays using the two world's most advanced automated cell metabolism analyzers and the automated normalization system, Cytation1, from Agilent Technologies Inc., and the three following specialized metabolic assays from Agilent: Mitochondrial Stress Test assay: This assay measures the baseline of the participant's mitochondrial functions by quantifying OXPHOS bioenergetic parameters. The investigators uses this assay to monitor the potential efficacy of oral administration of glycerol tributyrate in participants. Real-Time ATP Rate assay: The investigators use this assay to quantify the pathway-specific ATP rate production from the mitochondrial OXPHOS pathway and the cytosolic glycolytic pathway. Agilent Glycolytic Rate assay: The investigators use this assay to assess the metabolic plasticity between the two main energy pathways, OXPHOS and glycolysis,as well as to correlate one-on-one the glycolytic activity with lactate accumulation. No participants are enrolled in the dose-escalation phase without a complete interpretation of the clinical data from the baseline lead-in phase. As a higher level of safety risk, participants with the pre-existing severe complications, renal failure, arrhythmia, pneumonia with respiratory failure, and/or severe gastroparesis, will be excluded from progressing to the dose-escalating phase. During the six-month-long dose-escalation phase, the investigators will determine the safe participant-specific MTD using the toxicology and clinical data described above. Participants are administered glycerol tributyrate three times a day (tid) dispensed by the Children's National Hospital (CNH) research pharmacy located in the study site (CNH). To initiate the dose-escalation phase, the investigator provides all participants with a one-month supply of 100 capsules, each containing 500 mg of glycerol tributyrate. The initial dose is 1000 mg tid. During the last week of month 1 and subsequent months, the investigators review the clinical and biochemical data for each participant before increasing the oral dose of glycerol tributyrate. Below is the description of the methods to assess for dose-limiting toxicity (DLT) throughout the dose-escalation phase. 1. Disease-specific assessment: * For participants with MELAS, there are two measurable and reliable biomarkers for MELAS-specific upper threshold of the effect of the investigational drug: 1) plasma lactate levels greater than three times the normal levels; and 2) blood glucose levels above 200 mg/dl (11.1 mM). In addition, general toxicity is assessed in participants with MELAS as described in the criteria detailed below, which are shared by all participants. If general toxicity and/or MELAS-specific upper threshold of plasma lactate levels and blood glucose levels, MELAS participants will not be escalated to the next planned dose by 500 mg tid but rather re-treated at a one-dose concentration lower than the dose at which Grade 3 toxicity is encountered. * For participants with LHON-Plus, there are no similar reliable biomarkers for assessing such upper threshold. Therefore, these subjects will be closely monitored for general toxicity. 2. General toxicity assessment: The clinical investigators evaluate toxicity using the Common Terminology Criteria of Adverse Events (CTCAE) version 4.0 3 grading scale. * Dose-limiting toxicity (DLT) is defined as any of the adverse effects (AE) listed in Section 5.3.1.11 "Toxicity Monitoring" graded on the CTCAE v4.03. AE is considered possibly related to the investigational drug that occurs any time from the initial dose of glycerol tributyrate, when at grade 3 or higher, or worsening of baseline status as defined by increase of at least 2 grades, if baseline grade is less than or equal to 1. participants who develop Grade 3 or higher toxicity are re-treated at a one-dose concentration lower than the dose at which Grade 3 toxicity is encountered. * In the absence of DLT or in the case of CTCAE grade 1 or 2 toxicity, dose of glycerol tributyrate is escalated to the next planned dose by 500 mg tid. Doses are increased to the next planned dose by 500 mg tid every month until month 6 or prior if the participant-specific DLT is reached based on toxicity data using the CTCAE grading scale, as defined above. If participants reach their MTD prior to month 6 of the dose-escalating phase, they immediately enter the clinical phase at the fixed participant-specific MTD, defined as a one-dose concentration lower than the dose at which Grade 3 toxicity is encountered. At the conclusion of the dose-escalation phase, a skin biopsy will be performed on all participants prior to the onset of the clinical phase at fixed participant-specific MTD. The participant-specific dermal fibroblasts will be derived to determine the genetic and mitochondrial bioenergetic parameters for each participant at the outset of the clinical phase. The 12 month-long clinical phase at fixed participant-specific MTD starts at the conclusion of the 6-month-long dose-escalation phase and is divided into two 6-month-long periods. This 12-month-long time-frame is necessary to capture disease-specific clinical symptoms, to collect preliminary evidence of efficacy of glycerol tributyrate using disease-specific biomarkers, and to assess possible clinical outcomes demonstrating clinical benefit of glycerol tributyrate. At the outset, mid-phase, and end of the 12 month-long clinical phase, participants will undergo three skin biopsies to assess the potential efficacy of glycerol tributyrate on: 1. OXPHOS bioenergetic parameters 2. the clinical and biochemical target biomarkers. Throughout the clinical phase at fixed MTD, we will implement the same safety assessment for DLTs than for the dose-escalation phase. At the end of the 12-month-long clinical phase at fixed participant-specific MTD, the investigators will discharge the participants after performing a follow-up study during which non-serious adverse events or serious adverse events will be recorded for 7 or 30 days, respectively, after the last day of study participation. Capsules containing glycerol tributyrate (500 mg) will be administered orally to all participants three times a day with an 8-ounce glass of water on an empty stomach: morning, noon, and evening during the dose-escalation phase and the clinical phase at fixed subject-specific MTD of the study. Compliance will be assessed with an electronic log/diary where participants will record on a daily basis time, date, and pill counts. Participants will be asked to bring back all the bottles of glycerol tributyrate to subsequent visits to assess compliance. Compliance will be considered satisfactory with 80% of planned doses logged in. Participants will be specifically monitored for the occurrence of the following Adverse Events (AEs) graded based on the CTCAE v4.03: * Dizziness * Syncope * Concentration impairment * Fatigue * Fever * Nausea * Vomiting * Diarrhea * Hypoglycemia * Hyperglycemia * Lactic acidosis The investigators will review any AEs in person during the scheduled visits. The participants will also fill out a survey on their electronic diary to make it easier to capture any AEs. A Data and Safety Monitoring Board (DSMB) committee has been formed and includes five independent members: a metabolic physician, neurologist, bioethicist, a clinical trialist, and a lay person as a non-voting member. The DSMB committee will review safety data on an ongoing basis, meet biannually or ad-hoc if the need arises. This additional oversight provided by a DSMB committee provides further protection to the study participants during the basket clinical trial for MELAS and LHON-PLus.

Background: One-in-four Canadians will develop atrial fibrillation (AF), increasing risk of heart failure and stroke. Obesity (i.e., BMI ≥30 kg/m2) represents a strong, independent risk factor for increased incidence and severity of AF. Weight loss reduces AF symptom burden, and patients with obesity who lose ≥10% of their body weight may achieve AF regression/remission. Cardiac rehabilitation (CR) improves AF risk factors including hypertension and cardiorespiratory fitness (CRF), yet the efficacy of CR for reducing AF symptom burden is not established. CR rarely includes targeted obesity management and, on average, has a negligible impact on BMI. Adding behavioural weight-loss treatment (BWLT) to traditional CR may therefore enhance weight loss and lead to improvements in AF prognosis, symptoms, and health-related quality-of-life (HRQOL) in patients with AF and obesity. Given the high prevalence of obesity among individuals with AF, and its detrimental effect on AF burden and outcomes, there is a critical need for interventions that can support weight-loss-promoting behaviours and can be integrated into routine clinical care for AF. CR programs are available in all major Canadian cities and have a proven track-record of achieving clinically-relevant improvements in important AF risk factors including hypertension, lipid profile, and exercise capacity. Therefore, CR represents an ideal setting to promote risk factor management for patients with AF. Yet, because traditional CR does not produce meaningful weight loss there is a clear gap in the ability of current CR programming to meet the needs of a growing population of individuals with AF and obesity. The addition of a novel BWLT component to CR is needed to bridge this gap and provide the appropriate treatment regimen of comprehensive risk factor management, exercise, and weight loss to achieve optimal AF outcomes. The primary aim is to: Assess whether the combination of an AF-specific 'small changes' BWLT and traditional CR results in a greater proportion of patients with AF and obesity achieving ≥ 10% body weight loss compared to patients who receive standard care (traditional CR alone). The secondary aims of the proposed study are to evaluate the impact of BWLT+CR on: 1) mean % weight loss of controls vs. intervention group; 2) AF burden; 3) self-reported AF symptom burden; 4) disease-specific and generic patient-reported outcome measures (e.g., AF- and health-related quality-of-life \[HRQoL\]; psychological distress); and 5) exercise volume measured in weekly steps. Hypotheses: The primary study hypothesis is that patients in the BWLT+CR group will be more likely to achieve ≥10% weight loss at 12 months post-randomization relative to the CR-only group. Secondary hypotheses are that: patients in the BWLT+CR group will experience greater improvements in AF burden, AF self-reported symptom burden, increased HRQoL, decreased psychological distress, and increased leisure-time exercise and CR exercise session attendance relative to the CR-only group. Study design: Design and Procedure. Patients will be assessed for eligibility at TotalCardiology Rehabilitation (TCR). Eligible patients who consent to participate will be enrolled into the CR program and randomized to either the BWLT+CR or CR-only group. Prior to randomization, patients will complete a questionnaire battery including socio-demographic variables (age, sex, ethnicity, income, education), self-reported weight and height to establish BMI, and validated questionnaires assessing AF symptom burden, AF-related quality-of-life, general HRQOL, and psychological distress at baseline (T1). Patients will be re-administered the test battery following the 12-week BWLT+CR program, or 12 weeks of the CR-only program (T2). (Note: T2 measures will be administered even if the patient is still completing their remaining CR exercise sessions. CR completion/adherence will be determined after patients have completed their 12-week exercise program). The test battery will be administered for a final time approximately 24 weeks post-randomization. Weight loss from baseline to 52-weeks will be calculated and converted to a percentage of initial body weight at baseline. Clinical variables (e.g., CRF from graded exercise tests; blood pressure, lipids) will be obtained by TCR chart review. Recruitment. Patients will be recruited in two ways: (1) directly from TotalCardiology Rehabilitation using referrals from Dr. Wilton and TCR clinic staff, and (2) from an existing database of patients who participated in the Part I qualitative study and Part II acceptability study that provided consent to be contacted about future studies. The recruitment period will be from October 2022 to April 2024. Equal numbers of men and women will be recruited. AF clinic patients who are both (a) eligible for the CR program and (b) eligible for the proposed study will be identified by Dr. Wilton and/or TCR clinic staff. Dr. Wilton/TCR clinic staff will inform patients who meet (a) and (b) criteria about the study and invite them to participate. Interested patients will receive a CR referral and their contact information will be provided to the research coordinator. The research coordinator (B. Valdarchi) will contact patients, provide additional information about the study, and obtain informed consent. The research coordinator will then send an email link to complete baseline questionnaires. Following the completion of the questionnaires, participants will be informed about the group they were randomized to, and scheduled for BWLT groups if needed. Concurrently, patients will be contacted by CR staff to schedule their orientation appointment, as per typical clinic procedures. This recruitment procedure will also apply to patients who previously participated in Part I and II (i.e the qualitative and acceptability studies, respectively). TCR patients who are currently enrolled in CR will also be recruited. A research team member will identify CR patients who have consented to be approached about research and who are eligible for inclusion by reviewing patient chart data. An RA will contact patients by telephone to review study procedures and obtain patients' informed consent. Sample Size/Analysis. Analysis will be by intention to treat. Conservatively assuming a 5% success rate in the control group and a 30% success rate in the intervention group, 78 patients (39 per group) will provide 80% power to detect a difference using a two-sided independent test of proportions with a 5% significance level. The investigators estimate loss to follow-up and drop-outs of 20% and 10% respectively, therefore 120 patients will be recruited in total (60 per group). The primary analysis will compare the proportion in each group achieving ≥10% weight loss between baseline and 52 weeks post-randomization. A secondary per-protocol analysis will be performed including only participants who complete at least the initial 12-weeks of the BWLT. AF burden will be calculated as a % of total ECG tracings and compared between treatment and controls. Self-reported secondary outcomes will be evaluated using linear mixed modelling.

Acute lymphoblastic leukemia (ALL) has been referred to as a "pre-obese state", with many studies describing the onset of obesity during treatment. Weight gain typically begins within the first month of ALL diagnosis, stabilizes, and then resumes at the beginning of maintenance and continues into survivorship. Children and adolescents with healthy weight at diagnosis are the most vulnerable to weight gain; up to 70% develop overweight/obesity (OW/OB) by the end of treatment (EOT). Weight gain during treatment is one of the most consistently reported risk factors for weight gain in survivorship and is associated with an increased odds of being OW/OB 5-years post-EOT. Significant clinical ramifications are associated with being OW/OB. A meta-analysis led by the Children's Oncology Group nutrition committee found that OW/OB is associated with a 31% increased risk of mortality in ALL. The objective of the study team is to prevent the development of OW/OB during maintenance chemotherapy using a six-month virtually delivered dietary education intervention (PEDALL) in English and Spanish speaking families of children and adolescents undergoing treatment for ALL. Once enrolled, subjects will be randomized to PEDALL or standard of care (SOC). Subjects in the PEDALL group will receive 26 contact hours of specialized nutrition education and counseling via a virtual platform. The purpose of this study is to determine the effectiveness of a virtually-delivered dietary education intervention in the prevention of OW/OB compared to SOC during maintenance chemotherapy. The clinical impact of this study will improve the understanding of pre-treatment factors predictive of the efficacy of intervention to prevent unhealthy weight gain among patients treated for ALL. Study findings may lead to the allocation of limited clinical resources to individuals most susceptible to OW/OB. Information obtained from this study may also direct the refinement of counseling techniques to enhance the likelihood of success over the course of treatment for ALL and into survivorship. The long-term goal is to enhance the likelihood of success of weight maintenance during therapy thereby mitigating excess toxicities during treatment and reducing nutrition-related late-effects associated with OW/OB among survivors of childhood ALL.

Type 2 diabetes (T2D) is a disease commonly associated with obesity, which is an important risk factor for this condition. More than 80% of the diabetic subjects are obese. By analogy with the metabolic syndrome, the close association between obesity and T2D justifies the recognition of a new disease entity named by the neologism "diabesity". This study will examine the contribution of different genetic variants on "diabesity" development, by integrating multiple genomics approaches (linkage analysis on whole genome, transcriptomics and bioinformatics) and analysis of biological pathways in relevant animals models and humans.

The duration of treatment with GPB in this study was 5 years. Forty participants aged 0-18 years with a diagnosis of UCD, including carbamoyl phosphate synthetase I deficiency, ornithine carbamoyltransferase deficiency, citrullinemia type I, argininosuccinic aciduria, argininemia, or hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, and who plan to use and have not used glycerol phenylbutyrate in the previous 3 months (including 3 months) were enrolled. Participants should return to clinic visits at 1 month and 3 months after enrollment. They were queried about any adverse events (AEs), dosage change of the study drug or hyperammonemic crises (HACs) that occurred since the last visit, and blood samples were collected for the analysis of ammonia and blood biochemistry. Then the detailed information on AEs, dosage change of the study drug, HACs, and data about ammonia, routine clinical laboratory safety tests and neurocognitive outcomes that have been actually completed in the clinical practice of the patients will be collected every 6 months until 5 years. Height, weight and/or head circumference data were also collected at each visit. The assessments would be conducted at 1, 3, and 6 months, and subsequently on a semi-annual basis. The evaluation of ammonia levels, frequency of HACs, dosage of the study drug, AEs, serious AEs, and concomitant medications were included. The neurocognitive outcomes, growth and development of the participants would be described at the end.

The specific aim of this study is to examine the Safety, Tolerability and Pharmacokinetic of Semaglutide Nasal Spray compared with placebo and positive control in Adult Overweight or Obese Participants.

The main purpose of this study is to validate the effect of an individualized exercise prescription developed based on cardiopulmonary exercise testing (CPET) in subjects with metabolic syndrome. This study aims to assess the improvement in cardiovascular metabolic risk associated with the personalized exercise regimen,known as individualized HIIT.