Weight Reduction Therapy Research Articles

Strategies for minimizing muscle loss during use of incretin-mimetic drugs for treatment of obesity.

The rapid and widespread clinical adoption of highly effective incretin-mimetic drugs (IMDs), particularly semaglutide and tirzepatide, for the treatment of obesity has outpaced the updating of clinical practice guidelines. Consequently, many patients may be at risk for adverse effects and uncertain long-term outcomes related to the use of these drugs. Of emerging concern is the loss of skeletal muscle mass and function that can accompany rapid substantial weight reduction; such losses can lead to reduced functional and metabolic health, weight cycling, compromised quality of life, and other adverse outcomes. Available evidence suggests that clinical trial participants receiving IMDs for the treatment of obesity lost 10% or more of their muscle mass during the 68- to 72-week interventions, approximately equivalent to 20 years of age-related muscle loss. The ability to maintain muscle mass during caloric restriction-induced weight reduction is influenced by two key factors: nutrition and physical exercise. Nutrition therapy should ensure adequate intake and absorption of high-quality protein and micronutrients, which may require the use of oral nutritional supplements. Additionally, concurrent physical activity, especially resistance training, has been shown to effectively minimize loss of muscle mass and function during weight reduction therapy. All patients receiving IMDs for obesity should participate in comprehensive treatment programs emphasizing adequate protein and micronutrient intakes, as well as resistance training, to preserve muscle mass and function, maximize the benefit of IMD therapy, and minimize potential risks.

A very-low-calorie ketogenic diet normalises obesity-related enhanced levels of erythropoietin compared with a low-calorie diet or bariatric surgery

PurposeNutritional ketosis synergistically with body-weight loss induced by a very-low-calorie ketogenic diet (VLCKD) has proven to be effective in improving obesity-related pathophysiology. Recently, growing attention has been focused on the relation between erythropoietin (EPO) and obesity. Thus, this study aims to investigate whether nutritional ketosis and weight loss induced by a VLCKD modify the circulating levels of EPO in patients with obesity in comparison with the effect of low-calorie diet (LCD) or bariatric surgery (BS).MethodsEPO levels, iron status and body composition parameters were evaluated in 72 patients with overweight or obesity and 27 normal-weight subjects at baseline and after the three different weight-reduction therapies (VLCKD, LCD and BS) in 69 patients with excess body weight. β-hydroxybutyrate levels were also measured in the VLCKD group. The follow-up was established at 2–3 months and 4–6 months.ResultsIt was found that EPO levels were higher in morbid obesity and correlated with higher basal weight, fat mass (FM) and fat-free mass (FFM) in the overall sample. High baseline EPO levels were also correlated with higher impact on the course of weight loss and changes in FM and FFM induced by the three weight-loss interventions. Furthermore, the VLCKD induced a decrease in EPO levels coinciding with maximum ketosis, which was maintained over time, while statistically significant changes were not observed after LCD and BS.ConclusionThe obesity-related increased EPO levels are restored after VLCKD intervention at the time of maximum ketosis, suggesting a potential role of the nutritional ketosis induced by the VLCKD. Baseline EPO levels could be a biomarker of response to a weight-loss therapy.Graphical abstract

Factors influencing the bariatric surgery treatment of bariatric surgery candidates in underdeveloped areas of China

BackgroundFrom year to year, the proportion of people living with overweight and obesity in China rises, along with the prevalence of diseases linked to obesity. Although bariatric surgery is gaining popularity, there are still several issues with its promotion compared to Western nations. Since less developed places in China are more widespread due to disparities in the development of different regions, there has been little exploration of the factors that might be related to acceptance of bariatric surgery in these regions.MethodsPatients who visited the Department of Gastrointestinal Surgery at the North Sichuan Medical College Affiliated Hospital from 2018 to 2022 and had obesity or other relevant metabolic problems were surveyed using a questionnaire. The relationship between demographic factors, socioeconomic status, and acceptance of bariatric surgery was analyzed.ResultsOf 334 patients, 171 had bariatric surgery. BMI, education level, marriage history, medical insurance, family support, and a history of type 2 diabetes were all linked to having bariatric surgery, according to a univariate analysis. In a multivariate analysis, BMI (P = 0.02), education (P = 0.02), family support (P<0.001), medical insurance coverage (P<0.001), and history of type 2 diabetes (P = 0.004) were all positively associated with a willingness to have bariatric surgery. Among 163 non-bariatric patients with obesity, 15.3% were not opposed to surgery but preferred trying medication first, 54.6% leaned towards medical therapy, and 30% were hesitant. Additionally, a majority of patients (48.55%) often lacked adequate knowledge about weight reduction therapy. Age, height, gender, smoking, drinking, family history of type 2 diabetes, education, and marital status did not significantly differ (P > 0.05).ConclusionsMany patients are concerned about the safety of surgical treatment and the possibility of regaining weight. Due to the relatively high cost of bariatric surgery, they tend to choose medical treatment. To enhance the acceptance of bariatric surgery in underdeveloped regions of China, it is crucial to focus on disseminating knowledge about bariatric surgery, offer pertinent health education to the community, and foster support from patients’ families. The government should pay more attention to obesity and provide support in the form of medical insurance.

A Comparative Study of Cognitive Behavioral Therapy and Mindfulness-Based Cognitive Therapy for Weight Reduction and Activity Increase in Obese Individuals with Coronary Artery Disease

Obesity is a metabolic disorder and is often the cause of health problems such as cardiovascular diseases. The purpose of this preliminary study was to compare the efficacy of Cognitive Behavioral Therapy (CBT) with Mindfulness-Based Cognitive Therapy

Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity

BackgroundObesity is a major risk factor for many leading causes of illness and death worldwide. Data are needed regarding the efficacy and safety of the nonpeptide glucagon-like peptide-1 (GLP-1) receptor agonist orforglipron as a once-daily oral therapy for weight reduction in adults with obesity.MethodsIn this phase 2, randomized, double-blind trial, we enrolled adults with obesity, or with overweight plus at least one weight-related coexisting condition, and without diabetes. Participants were randomly assigned to receive orforglipron at one of four doses (12, 24, 36, or 45 mg) or placebo once daily for 36 weeks. The percentage change from baseline in body weight was assessed at week 26 (primary end point) and at week 36 (secondary end point).ResultsA total of 272 participants underwent randomization. At baseline, the mean body weight was 108.7 kg, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 37.9. At week 26, the mean change from baseline in body weight ranged from −8.6% to −12.6% across the orforglipron dose cohorts and was −2.0% in the placebo group. At week 36, the mean change ranged from −9.4% to −14.7% with orforglipron and was −2.3% with placebo. A weight reduction of at least 10% by week 36 occurred in 46 to 75% of the participants who received orforglipron, as compared with 9% who received placebo. The use of orforglipron led to improvement in all prespecified weight-related and cardiometabolic measures. The most common adverse events reported with orforglipron were gastrointestinal events, which were mild to moderate, occurred primarily during dose escalation, and led to discontinuation of orforglipron in 10 to 17% of participants across dose cohorts. The safety profile of orforglipron was consistent with that of the GLP-1 receptor agonist class.ConclusionsDaily oral orforglipron, a nonpeptide GLP-1 receptor agonist, was associated with weight reduction. Adverse events reported with orforglipron were similar to those with injectable GLP-1 receptor agonists. (Funded by Eli Lilly; GZGI ClinicalTrials.gov number, NCT05051579.)

Comprehensive home-based telerehabilitation in a morbidly obese male patient with severe obstructive sleep apnea. A case report.

Rehabilitation may be an effective additional treatment method in patients with obstructive sleep apnea (OSA). Physical exercise, weight reduction, pulmonary rehabilitation, and myofunctional therapy (MT) represent beneficial components of rehabilitation recommended as a possible adjunct to standard OSA treatment. A 54-year-old man with morbid obesity, long-lasting snoring, breathing pauses, frequent waking, as well as persistent drowsiness and fatigue during the day underwent polysomnography (PSG) to investigate suspected OSA. Severe OSA was confirmed by PSG and a 12-week comprehensive, home-based telerehabilitation program (tele-RHB program) along with continuous positive airway pressure (CPAP) therapy was implemented. The tele-RHB program included regular teleconsultations, aerobic-endurance training, MT, inspiratory and expiratory muscle training, as well as recommendations on proper nutrition, a healthy lifestyle, and behavioral changes. Following the treatment, the patient's quality of life (QoL), exercise capacity, lung function, and OSA severity significantly improved. The patient achieved an overall 19.9 kg reduction in weight, of which 16.2 kg was body fat, and his apnea-hypopnea index decreased by 42.6 episodes/hour. Our case report suggests that the comprehensive home-based tele-RHB program adjunct to CPAP therapy may be a novel approach for improving OSA severity, a patient's QoL, exercise capacity, lung function and body composition. It is important to note that such a program should be optional, however it may be needed to achieve the highest possible overall improvement in a patient's life. Further clinical investigations are needed to determine the therapeutic efficacy and clinical potential of this tele-RHB program.

Upper Airway Resistance Syndrome : An Underdiagnosed Sleep-related Breathing Disorder

Upper Airway Resistance Syndrome (UARS) is an example of sleep-related breathing disorders. UARS was first reported by Guilleminault in 1992 and it is known as excessive daytime sleepiness without obvious apnea or hypopnea that is characterized by more than 50% of respiratory effort related arousals (RERAs) during sleep. The prevalence of UARS was 15% in population in São Paulo. Although clinical manifestations, electroencephalogram (EEG) findings, and pathogenesis differ between UARS and OSA (Obstructive Sleep Apnea), it still sparked a debate among researchers as to whether UARS should be categorized as a distinct disorder. The International Classification of Sleep Disorders - Third Edition (ICSD3) integrated UARS into OSA diagnosis, resulting in underdiagnosed and undertreated patients with sleep-related breathing disorders who did not necessarily meet OSA criteria. Untreated UARS, on the other hand, has a variety of clinical consequences, including poor weight and height growth, daytime irritability, worsening of quality of life, and cardiovascular complications. Continuous positive airway pressure therapy, oral appliances, surgical management, weight reduction, and positional therapy are all considered as options in management of UARS.&#x0D;

The Clinical Manifestations of Polycystic Ovary Syndrome (PCOS) and The Treatment Options

Polycystic Ovary Syndrome is one of the most common endocrine disorders in females. It is important to diagnose early using the correct diagnostic criteria to ensure proper management and to reduce the long-term effects.To aggregate data on females diagnosed with PCOS and study the prevalence, symptoms, diagnostic criteria, and treatment options available till date for this syndrome.A thorough literature search of PubMed, Medline, and Google Scholar for data sources mentioning the symptoms and diagnostic criteria for PCOS in females to date is included in the study. A total of 61 articles were used and a total of 10 were excluded due to repetition of data or studies with sample sizes less than 70.Women clinically diagnosed with PCOS. The prevalence of PCOS was more common in woman aged 21-34 years and varied from 2.2% to 20% in different parts of the world. The most common symptoms found for PCOS were menstrual irregularities, hirsutism, weight gain, and insulin resistance. There are 3 diagnostic criteria currently being used to diagnose PCOS namely Ovulatory Dysfunction, Hyperandrogenism, and Polycystic Ovarian . The symptoms of PCOS vary greatly among women and so treatment is largely based on the presentation of symptoms and prevention of long-term effect. Therefore, the main treatment options for menstrual irregularities areClomiphene Citrate, Letrozole, Oral Contraceptive Pills (OCPs) a second-line therapy includes Gonadotropins, Metformin and Laparoscopic Ovarian Drilling (LOD). Hyperandrogenism treatment options are Finasteride, Isotretinoin, Spironolactone and Flutamide. Simultaneously weight reduction therapy, lifestyle changes can be used to reduce a weight gain.The prevalence of PCOS is influenced the diagnostic criteria used. The Clinical presentations of PCOS vary greatly among women. Rotterdam criteria, most widely used to diagnose PCOS, include the presence of at least two of these three conditions: polycystic ovaries on ultrasound imagining; hyperandrogenism; and chronic ovulatory dysfunction. The treatment of PCOS is not specific. Lifestyle modifications, pharmacotherapy and some surgical approaches have been successfully used to manage the symptoms.

Effects of Weight Reduction Therapies on Lean Body Mass in Overweight and Obese People: A Meta-Regression Analysis

Effects of Weight Reduction Therapies on Lean Body Mass in Overweight and Obese People: A Meta-Regression Analysis

Differences in metabolic characteristics between Metabolically Healthy Obesity (MHO) and Metabolically Unhealthy Obesity (MUO) in weight reduction therapy.

Metabolically Healthy Obesity (MHO) is generally recognized as the absence of any metabolic disorders and cardiovascular diseases, including type 2 diabetes, dyslipidemia, and hypertension, in obese individuals; however, it is not clearly defined. Therefore, the present study investigated differences in metabolic characteristics between individuals with MHO and Metabolically Unhealthy Obesity (MUO) during weight reduction therapy. The key factors defining MHO and the importance of weight reduction therapy for MHO were also examined. Cohort data from the Japan Obesity and Metabolic Syndrome (JOMS) study were analyzed. Subjects were divided into the MHO (n = 25) and MUO (n = 120) groups. Prior to weight reduction therapy, serum adiponectin levels were significantly higher in the MHO group than in the MUO group. Serum adiponectin levels also negatively correlated with the area of subcutaneous adipose tissue (SAT) and Homeostasis model assessment (HOMA)-R in the MHO group, but not in the MUO group. Collectively, the present results suggest the importance of adiponectin for maintaining metabolic homeostasis in the MHO group. On the other hand, no significant differences were observed in inflammatory markers between the MHO and MUO groups, suggesting the presence of chronic inflammation in both groups. Furthermore, a positive correlation was noted between changes in serum cystatin C levels and waist circumference in the MHO group, which indicated that despite the absence of metabolic disorders, the MHO group exhibited anti-inflammatory responses during weight reduction therapy. These results underscore the significance of weight reduction even for individuals with MHO.

Remission as an Emerging Therapeutic Target in Type 2 Diabetes in the Era of New Glucose-Lowering Agents: Benefits, Challenges, and Treatment Approaches.

Type 2 diabetes mellitus (T2DM) is a progressive disease with a growing prevalence, associated with an increased risk of complications. The introduction of new classes of antidiabetic drugs into clinical practice has dramatically changed the landscape of diabetes therapy. However, despite the progress made in the pharmacotherapy of T2DM, mitigating the burden of the disease on individuals, societies and health care systems remains a challenge. Remission has recently emerged as a therapeutic target in T2DM, achievable through a wide range of interventions. Recent studies have shown that extensive lifestyle changes, such as weight reduction, bariatric surgery, and intensive glucose lowering therapy, can prompt the remission of diabetes, but some unanswered questions remain regarding its long-term effects on diabetic complications. Metabolic surgery and novel classes of glucose-lowering medications are currently the most effective interventions to induce weight loss and by extension remission in patients with diabetes; however, the ideal strategy to achieve the long-term maintenance of remission remains doubtful. In this narrative review, we discuss the available therapeutic approaches to target the remission of diabetes through personalized multimodal care, based on the latest evidence.

Analysis of time-dependent changes in the FIB4 index in patients with obesity receiving weight reduction therapy

Weight reduction therapy represents a fundamental strategy to prevent nonalcoholic fatty liver disease (NAFLD) in patients with obesity, which may result in liver fibrosis. Histological findings previously demonstrated that weight reduction therapy attenuated NAFLD. The FIB4 index is widely used to assess the status of NAFLD. The present study investigated whether the FIB4 index improved during weight reduction therapy. We used cohort data of the Japan Obesity and Metabolic syndrome Study and examined the correlation between body weight (BW) loss (BW loss) and changes in the FIB4 index (ΔFIB4 index) in patients who successfully reduced their BW by more than 5% from baseline BW after 3, 6, and 12 months (M) of weight reduction therapy. A negative correlation (r = −0.342, p = 0.029) was observed between BW loss and FIB4 index after 3 M, but not after 6 M, whereas a positive correlation (r = 0.298, p = 0.03) was noted after 12 M. These results revealed changes in the correlation between ΔBW loss and ΔFIB4 index during the therapy, mainly due to time-dependent changes in components of the FIB4 index formula. Thus, we concluded that the FIB4 index is useful and reliable to assess liver fibrosis until 3 M during weight reduction therapy. However, after 3 M, we should recognize that the FIB4 index may not reflect liver status. Therefore, it is important to consider this characteristic of the FIB4 index as a limitation when assessing liver fibrosis in obese patients receiving weight reduction therapy.

Updates in the Epidemiology of Fatty Liver and its Consequences in Saudi Arabia: A Review

The occurrence of non-alcoholic fatty liver disease has exponentially increased worldwide. A considerable majority of cases advance to non-Alcoholic Steatohepatitis in the nonexistence of therapeutic measures, which increases morbidity and death. Because the initial phases of the illness are frequently clinically unapparent, the identification of non-alcoholic fatty liver disease frequently rests on biochemical and radiographic studies. Concentrated life modifications that result in weight loss are the mainstay of the disease's management. Therapeutic treatments that could be additional to lifestyle changes once essential for case managing comprise insulin sensitizers, antioxidants, incretin-based pharmaceuticals, cholesterol depressing mediators, weight reduction therapies, bariatric surgery, and liver transplantation. For non-alcoholic fatty liver disease to be managed more effectively and lessen its worldwide impact, research must be conducted continuously.

Immunomodulatory effect of a very-low-calorie ketogenic diet compared with bariatric surgery and a low-calorie diet in patients with excessive body weight

<h2>Summary</h2><h3>Background & aim</h3> Inflammation and oxidative stress are the most probable mechanistic link between obesity and its co-diseases with cancer among them. The aim of this study was to evaluate whether the nutritional ketosis and weight loss induced by a very-low-calorie ketogenic diet (VLCKD) modulates the inflammatory and oxidative stress profile, compared with a standard, balanced hypocaloric diet (LCD) or bariatric surgery (BS) in patients with obesity. <h3>Methods</h3> The study was performed in 79 patients with overweight or obesity and 32 normal-weight volunteers as the control group. Patients with obesity underwent a weight reduction therapy based on VLCKD, LCD or BS. The quantification of the circulating levels of a multiplexing test of cytokines and carcinogenesis/aging biomarkers, as well as of lipid peroxides and total antioxidant power, was carried out. <h3>Results</h3> First, we observed that pro-inflammatory cytokines increase, while anti-inflammatory cytokines decrease under excessive body weight. Relevantly, when patients underwent weight loss strategies, it was shown that energy-restricted and surgical strategies of weight loss induced changes in circulating cytokine and lipid peroxides. This effect was more notable in patients following the VLCKD than the LCD or BS and it was observed mainly in the ketosis phase of the intervention. Particularly, IL-11, IL-12, IL-2, INF-γ, INF-β, Pentraxin-3 or MMP1 changed after VLCKD. Whereas, APRIL, TWEAK, osteocalcin and IL-28A increased after BS. <h3>Conclusion</h3> As far as we know, this is the first study that evaluate the time-course of cytokines and oxidative stress markers after a VLCKD as compared with a standard LCD and BS. The observed results support the immunomodulatory effect of nutritional ketosis induced by a VLCKD synergistically with weight loss as a strategy to improve innate-immunity and to prevent infections and carcinogenesis in patients with obesity.

Successful correction of hyperglycemia is critical for weight loss and a decrease in cardiovascular risk in obese patients

Weight loss is recommended for obese patients with cardiovascular risk; however, it remains questionable how hyperglycemia affects this process. To address this problem, we aimed to determine the association between weight loss, lipid profile, and body mass parameters in obese normoglycemic and hyperglycemic patients. Obese (body mass index30 kg/m2) normoglycemic and hyperglycemic volunteers were placed on a weight reduction program that included a balanced, low-calorie diet and moderate exercise for 6 months. Participants were assessed for serum glucose, β-cell functions, insulin resistance, lipid metabolism, lipoprotein profile, and body mass parameters. This weight reduction program fully normalized serum glucose levels only in a subpopulation of patients. These individuals also exhibited a significant reduction in body weight, and significant improvement in serum lipid profile and insulin resistance. In contrast, the patients that remained hyperglycemic were characterized by persistent insulin resistance, increased levels of atherogenic fractions of LDL and HDL lipoproteins, and elevated values of a modified Atherogenic Index of Plasma. Correlation analysis indicated a strong positive association between the modified Atherogenic Index of Plasma with atherogenic lipid profile, insulin resistance, and body mass parameters, indicating its usefulness in clinical studies in obese patients. Overall, our data indicate that successful treatment of hyperglycemia facilitates weight loss and improves the composition of blood lipids, while persisting hyperglycemia negatively affects the weight loss process and maintains an atherogenic lipid profile. Because hyperglycemia predisposes to cardiovascular disorders, its correction should be the primary goal during weight reduction therapy.

Randomised, placebo-controlled trial on topiramate add-on therapy for weight reduction and symptomatology in overweight/obese persons with schizophrenia.

Higher cardiovascular mortality is seen with schizophrenia due to the disorder itself and antipsychotic use. South Asians are more vulnerable to developing metabolic disorders than others. Resource-limited settings in South Asia have only a few mental health professionals, and individualised case management is mostly unavailable. Therefore, there is less monitoring and personalised support for diet and physical exercise programmes. Topiramate is useful for weight reduction and improvement of psychopathology in schizophrenia. However, there has been only one previous randomised controlled trial (RCT) done in South Asia, which possesses a quarter of the world's population. We conducted a double-blind RCT in an outpatient setting in Sri Lanka. We compared topiramate 100mg/day with a placebo in overweight/obese adults with schizophrenia who have been on antipsychotics for at least a year. We obtained monthly anthropometric measurements and assessed the symptomatology using the brief psychiatric rating scale (BPRS). Fifty patients each in the topiramate and placebo arms completed the study. Topiramate add-on therapy led to significant weight/Body Mass Index reduction and improved symptomatology as measured by the BPRS compared to the placebo. The topiramate group had significantly more reporting of loss of appetite. According to available data, this is the RCT with most participants assessing the use of topiramate in schizophrenia and only the second in South Asia. Topiramate was shown to be useful for weight reduction and symptomatic improvement in persons with schizophrenia in a resource-limited setting in South Asia.

Ketogenic diet, African American women, and cardiovascular health: A systematic review.

Cardiovascular disease (CVD) is the number one cause of death in the United States of America and across the world. The high prevalence of obesity (56.9%) in African American women contributes to high rates of CVD. Ketogenic nutritional therapy has been shown to be a safe and effective therapy for weight loss and reduction in other CVD risk factors (e.g., HgbA1C and blood pressure). However, the evidence investigating ketogenic nutritional therapy among African American women to improve CVD risk factors has not yet been synthesized. To conduct a systematic review of the evidence on CVD risk reduction and ketogenic nutrition therapy among African American women. CINAHL Plus, Cochrane, EMBASE, MEDLINE/PubMed, SCOPUS, and Web of Science were searched for quantitative studies focused on ketogenic nutritional therapy and CVD risk factors among African American women. Included studies measured beta-hydroxybutyrate as an indicator of dietary adherence. Of 4,799 articles identified, six articles representing five studies were included in this review. The majority of participants were female, with very few identified as African American women. Primary outcomes included weight, body mass index (BMI), blood pressure, and lipids. Dietary adherence was difficult to assess. Significant reductions in weight and BMI were noted. Heterogeneity in study design, intervention length, and measurement of dietary adherence made generalizations difficult. Few studies continually monitored dietary adherence using beta-hydroxybutyrate levels, thus threatening the internal validity of the studies. A gap in our understanding remains concerning CVD risk and ketogenic nutritional therapy among African American women specifically. Ketogenic nutritional therapy is effective in women to reduce weight and BMI. Ketogenic nutritional therapy may be beneficial in reducing CVD risk factors. Monitoring dietary adherence using beta-hydroxybutyrate levels with commercially available monitors is key to intervention success.

Hyperandrogenism and menstrual imbalance are the best predictors of metformin response in PCOS patients

BackgroundMoving from the correlation between insulin-resistance and PCOS, metformin has been administered in some PCOS women improving ovulatory and metabolic functions and decreasing androgen levels. Inconsistency and unpredictability of response to metformin limit its extensive use. Aim of this study was to identify reliable predictors of response to metformin therapy for weight loss and reduction in plasma androgen levels using ANNs (artificial neural networks).MethodsOne hundred eight consecutive women with PCOS (ESHRE/ASRM 2003 Rotterdam criteria) treated with metformin 1500 mg/day, at inclusion and every 6 months underwent to a complete clinical, endocrine/metabolic assessment and ultrasonographic evaluation. Therapy outcomes were BMI reduction (≥1 kg/m2) in overweight/obese and free-androgen-index (FAI) decrease (≥1%) in hyperandrogenemic women. Semantic connectivity maps (SCMs) were obtained through Auto-CM, a fourth generation ANN, to compare patients’ baseline clinical features to the treatment outcomes. Multivariate logistic regression analysis was used to assess the major predictor in drop-out patients and the associated risk.ResultsAt 6 months 54 out of 103 (52,4%) obese patients showed BMI reduction and 45 out of 89 (50,6%) hyperandrogenemic women showed FAI decrease. The further response rates at 12 months were 30,6 and 47%, respectively. SCMs showed a clear polarization for both the outcomes with elevated accuracy. Treatment responsiveness resulted strictly related to oligo-amenorrhea and hyperandrogenemia at baseline. In addition, lower serum testosterone levels at baseline were found to be the major predictor of treatment discontinuation.ConclusionsIn women with PCOS, menstrual pattern imbalance and ovarian androgens excess are the best predictors of metformin response. They may pave the way for a rethinking of the criteria for evaluating hyperandrogenism in order to better define the large population included in the diagnosis of PCOS. Baseline plasma testosterone level can serve as a sensitive marker to predict treatment compliance.

Adipose tissue and blood leukocytes ACE2 DNA methylation in obesity and after weight loss.

Obesity was consistently associated with a poor prognosis in patients with COVID-19. Epigenetic mechanisms were proposed as the link between obesity and comorbidities risk. To evaluate the methylation levels of angiotensin-converting enzyme 2 (ACE2) gene, the main entry receptor of SARS-CoV-2, in different depots of adipose tissue (AT) and leukocytes (PBMCs) in obesity and after weight loss therapy based on a very-low-calorie ketogenic diet (VLCKD), a balanced hypocaloric diet (HCD) or bariatric surgery (BS). DNA methylation levels of ACE2 were extracted from our data sets generated by the hybridization of subcutaneous (SAT) (n=32) or visceral (VAT; n=32) adipose tissue, and PBMCs (n=34) samples in Infinium HumanMethylation450 BeadChips. Data were compared based on the degree of obesity and after 4-6months of weight loss either by following a nutritional or surgical treatment and correlated with ACE2 transcript levels. As compared with normal weight, VAT from patients with obesity showed higher ACE2methylation levels. These differences were mirrored in PBMCs but not in SAT. The observed obesity-associated methylation of ACE2 was reversed after VLCKD and HCD but not after BS. Among the studied CpG sites, cg16734967 and cg21598868, located at the promoter, were the most affected and correlated with BMI. The observed DNA methylation pattern was inversely correlated with ACE2 expression. Obesity-related VAT shows hypermethylation and downregulation of the ACE2gene that is mirrored in PBMCs and is restored after nutritional weight reduction therapy. The results warrant the necessity to further evaluate its implication for COVID-19 pathogenesis.

CT Cisternogram Findings in Idiopathic Cerebrospinal Fluid Leaks with Emphasis on Long Term Management.

To study the various computed tomography (CT) cisternogram findings in idiopathiccerebrospinal fluid (CSF) leaks and the long term treatment modalities after surgical repair of idiopathic CSF leaks. This was a descriptive study conducted among 25 patients in MCV memorial ENT trust hospital, Pollachi between May 2014 and May 2020 amongst patients who underwent CT cisternogram for unilateral or bilateral spontaneous rhinorrhea with or without associated headache, visual disturbances and papilloedema diagnosed to be idiopathic CSF leak by investigations. These patients then underwent CSF leak repair and postoperatively were managed with weight reduction, low salt diet and diuretic therapy. Post surgery these patients were followed up for a period of 12months and were evaluated on the basis of presence or absence of headache, rhinorrhea and papilloedema at the end of 1st month, 3rd month, 6th month and 1year and data was collected. CT cisternogram findings were evaluated by proportion method and evaluation of long term management was done using proportion and repeated measures ANOVA for all patients. Evidence of the presence of previously mentioned CT cisternogram or contrast MRI findings at the end of 1year of post-surgical treatment was recorded where patients were willing for the same. CT Cisternography was done for all patients and 72% patients had empty sella appearance while 28% had partially empty sella. Other findings included perioptic filling, optic blunting and arachnoid pits which were found in 11(44%), 8(32%) and 12(48%) of patients respectively. Only 3(12%) out of 25 patients had an encephalocoele. The commonest site of leak in CT cisternography was the cribriform plate (52%) followed by lateral recess of sphenoid (48%). None of the patients had multiple sites of leak in CT cisternography. On follow up post surgery maximum resolution of symptoms was found at the end of 12months where 23 out of 25 patients improved. In our study, out of 25 only 5 patients agreed to undergo post diuretic therapy MRI scan out of which 2 patients had partially empty sella and 3 had normal sella indicating resolution of BIH. CT cisternography is an important investigation which aids in the diagnosis of CSF rhinorrhea due to idiopathic intracranial hypertension (IIH). The medical management of IIH post surgery such as weight reduction, salt restriction and diuretic therapy is also crucial to prevent recurrence of symptoms.