Total and H-specific growth/differentiation factor 15 levels are unaffected by liraglutide or naltrexone/bupropion administration.

AIM: To investigate growth/differentiation factor 15 (GDF-15) levels in response to antiobesity medications, namely, liraglutide (Lira) and naltrexone/bupropion (N/B), in individuals with overweight or obesity. MATERIALS AND METHODS: This was a prospective, non-randomized clinical trial with a two-arm, parallel design. A total of 42 individuals with overweight or obesity without type 1 or type 2 diabetes mellitus were enrolled. The participants received either Lira 3 mg or N/B 32/360 mg, along with diet and exercise, according to comorbidities, cost and method of administration. Participants underwent clinical and laboratory measurements at baseline, as well as at the 3- and 6-month time points. Anthropometric measurements and body composition analysis via bioelectrical impendence analysis were performed. Total blood samples for GDF-15 and H-specific GDF-15 were collected in the fasting state and every 30 min for 3 h after the consumption of a standardized mixed meal. RESULTS: Overall, participants' weight was reduced by 9.29 ± 5.34 kg at Month 3 and 11.52 ± 7.52 kg at Month 6. Total and H-specific GDF-15 levels did not show significant changes during the mixed meal compared to values before the meal when all participants were examined at baseline, and at 3 and 6 month follow-ups. No statistical significance was found when participants were examined by subgroup (Lira vs. N/B). No significant differences between treatment groups in postprandial area under the curve (AUC) or incremental AUC values were found at baseline or in the follow-up months with regard to total and H-specific GDF-15 levels. CONCLUSION: Neither total nor H-specific GDF-15 levels are affected by Lira or N/B treatment in patients with overweight or obesity.

The effect of obesity pharmacotherapy on body composition, including muscle mass.

Obesity pharmacotherapy represents a promising approach to treating obesity and may provide benefits beyond weight loss alone. Maintaining or even increasing muscle mass during weight loss is important to overall health, metabolic function and weight loss maintenance. Drugs such as liraglutide, semaglutide, tirzepatide, and naltrexone/bupropion have shown significant weight loss effects, and emerging evidence suggests they may also have effects on body composition, particularly a positive influence on muscle mass. However, further research is needed to fully understand the mechanism of action of these drugs and their effects on muscle mass. Clinicians should consider these factors when developing an obesity treatment plan for an individual patient.

The Effects of Bariatric Surgery on Pharmacokinetics of Drugs: a Review of Current Evidence.

PURPOSE OF REVIEW: Obesity constitutes a major public health concern and has been recognized as an epidemic. To date, bariatric surgery remains the most effective way for substantial long-lasting weight loss in severe obesity. The purpose of this review is to summarize how the pharmacokinetics of drugs are affected by the most common types of bariatric surgery, i.e., Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). RECENT FINDINGS: Limited data are available regarding the changes in pharmacokinetics of drugs after bariatric surgery. The lack of existing guidelines may lead patients to experience drug toxicity or therapeutic undertreatment. Pharmacokinetic parameters that need to be taken into consideration postoperatively include gastric motility, gastric volume, pH, surface area, bile secretions, carrier proteins, and first-pass metabolism. For drugs with a narrow therapeutic index, other factors need to be monitored closely, including plasma drug levels, patients' clinical outcomes, and laboratory markers. Patients should be followed up frequently and treated in accordance with their response to the drug therapy. Bariatric surgery may affect the pharmacokinetics of various drugs, due to the resultant anatomical changes and the substantial weight loss. Therefore, there is a need to identify those potential changes and adjust patients' medication doses in order to achieve higher efficacy and avoid toxicity.

Circulating levels of all proglucagon-derived peptides are differentially regulated postprandially by obesity status and in response to high-fat meals vs. high-carbohydrate meals.

BACKGROUND & AIMS: We measured all proglucagon-derived peptides (PGDPs) levels in response to administration of three mixed meal tolerance tests (MMTs), examining differences in postprandial PGDP responses in subjects with leanness and obesity or between high-fat vs. high carbohydrate meals. METHODS: We designed three physiology interventional studies, administering MMTs over a 180-min period to individuals without diabetes after an overnight fast. In Study 1, a 450 kcal MMT was administered to n = 4 normal weight and n = 9 individuals with obesity. In Study 2, a 600 kcal high-fat MMT was administered to n = 15 normal-weight and n = 15 individuals with obesity. In Study 3, n = 32 participants with obesity were assigned to receive a 600-kcal high-fat (n = 15) or an isocaloric high-carbohydrate MMT (n = 17). Fasting and postprandial levels of c-peptide and PGDPs (proglucagon, GLP-1, GLP-2, glicentin, oxyntomodulin, glucagon, major proglucagon fragment [MPGF]) were assessed. RESULTS: In study 1, individuals with normal weight displayed elevated glicentin postprandial secretion compared with people with obesity (p = 0.002). Following a high-fat MMT with 33% higher energy content in study 2, all postprandial PGDPs levels were elevated (p-time<0.001), irrespective of weight status. In study 3, a prolonged postprandial upregulation of PGDPs during the high-fat MMT was observed in contrast with the acute, short-term (max 60 min) PGDP responses to a high-carbohydrate MMT (p-time∗meal<0.001). Across both studies 2 and 3, the postprandial responses of glucagon and MPGF were higher in subjects with male sex whereas glicentin was higher in subjects with female sex. CONCLUSIONS: Fat and carbohydrate content of a meal can substantially affect the postprandial levels of PGDPs. Circulating levels of PGDPs are influenced by the energy content of the meal, and additionally, the presence of leanness or obesity affects circulating levels of select PGDPs. These results, which are to be confirmed by additional studies, expand our understanding of PGDP physiology in leanness and obesity. CLINICALTRIALS: GOV REGISTRATION NUMBERS: (NCT04170010, NCT04430946, NCT04575194).

Circulating levels of proglucagon-derived peptides are differentially regulated by the glucagon-like peptide-1 agonist liraglutide and the centrally acting naltrexone/bupropion and can predict future weight loss and metabolic improvements: A 6-month long interventional study.

AIM: To investigate the changes of circulating levels of all proglucagon-derived peptides (PGDPs) in individuals with overweight or obesity receiving liraglutide (3 mg) or naltrexone/bupropion (32/360 mg), and to explore the association between induced changes in postprandial PGDP levels and body composition, as well as metabolic variables, after 3 and 6 months on treatment. MATERIALS AND METHODS: Seventeen patients with obesity or with overweight and co-morbidities, but without diabetes, were assigned to receive once-daily oral naltrexone/bupropion 32/360 mg (n = 8) or once-daily subcutaneous liraglutide 3 mg (n = 9). Participants were assessed before treatment initiation and after 3 and 6 months on treatment. At the baseline and 3-month visits, participants underwent a 3-hour mixed meal tolerance test to measure fasting and postprandial levels of PGDPs, C-peptide, hunger and satiety. Clinical and biochemical indices of metabolic function, magnetic resonance-assessed liver steatosis and ultrasound-assessed liver stiffness were measured at each visit. RESULTS: Both medications improved body weight and composition, carbohydrate and lipid metabolism, and liver fat and function. Naltrexone/bupropion produced a weight-independent increase in the levels of proglucagon (P < .001) and decreases in glucagon-like peptide-2 (GLP-2), glucagon and the major proglucagon fragment (P ≤ .01), whereas liraglutide markedly upregulated total glucagon-like peptide-1 (GLP-1) levels in a weight-independent manner (P = .04), and similarly downregulated the major proglucagon fragment, GLP-2 and glucagon (P < .01). PGDP levels at the 3-month visit were positively and independently correlated with improvements in fat mass, glycaemia, lipaemia and liver function, and negatively with reductions in fat-free mass, at both the 3- and 6-month visits. CONCLUSIONS: PGDP levels in response to liraglutide and naltrexone/bupropion are associated with improvements in metabolism. Our study provides support for the administration of the downregulated members of the PGDP family as replacement therapy (e.g. glucagon), in addition to the medications currently in use that induced their downregulation (e.g. GLP-1), and future studies should explore whether the addition of other PGDPs (e.g. GLP-2) could offer additional benefits.

Nutritional Deficiencies Before and After Bariatric Surgery: Prevention and Treatment.

PURPOSE OF REVIEW: Bariatric surgery has the unique ability to drive substantial and sustainable weight loss in people living with obesity. Non-reversibility of these surgical techniques provides lifelong benefits but entails the need for continuous medical follow-up. The purpose of the current paper is to review and summarize current data on nutritional deficiencies in patients before and after bariatric surgery. RECENT FINDINGS: The cornerstone of preventing the emergence of disorders related to nutritional deficiencies is preoperative screening and correct supplementation since they may be exacerbated postoperatively. Following guidelines in conjunction to a lifelong personalized medical approach is of high importance. Bariatric surgery is a well-studied successful and durable means of weight loss that may lead to nutritional deficiencies. There is, thus, a medical need for careful monitoring and treatment of micro- and macronutrient deficiencies by an experienced multidisciplinary team.

Interplay between baroreflex sensitivity, obesity and related cardiometabolic risk factors (Review).

The baroreflex represents a rapid negative feedback system implicated in blood pressure regulation, which aims to prevent blood pressure variations by regulating peripheral vascular tone and cardiac output. The aim of the present review was to highlight the association between baroreflex sensitivity (BRS) and obesity, including factors associated with obesity, such as metabolic syndrome, hypertension, cardiovascular disease and diabetes. For the present review, a literature search was conducted using the PubMed database until August 21, 2021. The searched terms included 'baroreflex', and other terms such as 'sensitivity', 'obesity', 'metabolic syndrome', 'hypertension', 'diabetes', 'gender', 'aging', 'children', 'adolescents', 'physical activity', 'bariatric surgery', 'autonomous nervous system' and 'cardiometabolic risk factors'. Obesity and its related metabolic disorders can influence baroreflex functionality and decrease BRS, mostly by potentiating sympathetic nervous system activity. Obesity induces inflammation, which can increase sympathetic system activity and lead to a higher incidence of cardiovascular events. Obesity also represents an important risk factor for hypertension through numerous mechanisms; in this setting, dysfunctional baroreceptors are not able to protect against constantly elevated blood pressure. Furthermore, diabetes mellitus and oxidative stress result in deterioration of BRS, whereas aging is also generally related to reduced cardiovagal BRS. Differences in BRS have also been observed between men and women, and overall cardiovagal BRS in healthy women is less intense compared with that in men. BRS appears lower in children with obesity compared with that in children of a healthy weight. Notably, physical exercise can increase BRS in both hypertensive and normotensive subjects, and BRS can also be significantly improved following bariatric surgery and weight loss. In conclusion, obesity and its related metabolic disorders may influence baroreflex functionality and decrease BRS, and baroreceptors cannot protect against the constantly elevated blood pressure in obesity. However, following bariatric surgery and weight loss, BRS can be significantly improved. The present review summarizes the role of obesity and related metabolic risk factors in BRS, providing details on possible mechanisms and shedding light on their interplay leading to autonomic neuropathy.

Pineal hormone melatonin as an adjuvant treatment for COVID­19 (Review).

The beneficial properties of the pineal hormone, melatonin, as a neuroprotective and cardioprotective agent, have been previously identified. Furthermore, melatonin plays essential roles in biological rhythms resynchronization, sleep initiation/maintenance and metabolic, ocular, rheumatological diseases. In addition to these functions, melatonin is known to exert immunomodulation, anti­inflammatory and anti­oxidative effects. Due to these properties, coupled with its non­toxic nature, melatonin has been suggested to limit viral infections; however, melatonin cannot be classified as a viricidal drug. In addition, the recent increase in the number of clinical trials on melatonin's role, as an adjuvant treatment for COVID­19, has resurged the interest of the scientific community in this hormone. The present short review aimed to improve the understanding of the antiviral/anti­COVID­19 profile of melatonin and the clinical trials that have recently been conducted, with respect to its co­administration in treating individuals with COVID­19.

A retrospective study on the evaluation of the symptoms, medications and improvement of the quality of life of patients undergoing robotic surgery for gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder requiring lifestyle adaptations and administration of medications. Another approach is the surgical treatment of GERD through laparoscopic or robotic operations. The aim of the present study was to investigate the improvement of symptoms and quality of life of patients with GERD, before and after robotic surgical restoration using the Nissen robotic fundoplication technique. The potential effects of body weight, age and sex, as well as the response to medications and progress over time, were also assessed. A retrospective study was conducted in a tertiary hospital between October 2019 and March 2020. Data were collected and recorded from 144 patients who underwent robotic surgery, using the Nissen fundoplication technique, during the period 2009-2019. All patients involved in this analysis pre-operatively exhibited severe symptoms of heartburn and reflux, as well as poor quality of life. All of these symptoms were re-examined after surgery, and a marked decrease was observed with respect to their frequency and intensity. Improvement was not affected by body mass index, whereas older patients exhibited greater improvement. Women initially experienced more severe symptoms before the surgery, but they appeared to respond as well as the male patients. The long-term beneficial effects of surgery for up to the 10-year period studied were validated. After the robotic surgical rehabilitation, the vast majority of patients overcame the unpleasant symptoms of GERD and stayed off their medications. More than 4/5 of the patients were satisfied after surgery. In conclusion, restoration of GERD, using Nissen robotic fundoplication, led to the minimization of symptoms and to a marked improvement in the quality of life of patients.

Successful Outflow Reconstruction to Salvage Traumatic Hepatic Vein-Caval Avulsion of a Normothermic Machine Ex-Situ Perfused Liver Graft: Case Report and Management of Organ Pool Challenges.

Donor organ shortage continues to limit the availability of liver transplantation, a successful and established therapy of end-stage liver diseases. Strategies to mitigate graft shortage include the utilization of marginal livers and recently ex-situ normothermic machine perfusion devices. A 59-year-old woman with cirrhosis due to primary sclerosing cholangitis was offered an ex-situ machine perfused graft with unnoticed severe injury of the suprahepatic vasculature due to road traffic accident. Following a complex avulsion, repair and reconstruction of all donor hepatic veins as well as the suprahepatic inferior vena cava, the patient underwent a face-to-face piggy-back orthotopic liver transplantation and was discharged on the 11th postoperative day after an uncomplicated recovery. This report illustrates the operative technique to utilize an otherwise unusable organ, in the current environment of donor shortage and declining graft quality. Normothermic machine perfusion can definitely play a role in increasing the graft pool, without compromising the quality of livers who had vascular or other damage before being ex-situ perfused. Furthermore, it emphasizes the importance of promptly and thoroughly communicating organ injuries, as well as considering all reconstructive options within the level of expertise at the recipient center.

Long-term survival with repeated resections of recurrent hepatocellular carcinoma in a non-cirrhotic liver: case report and brief review of the literature.

A healthy and asymptomatic 55-year-old woman underwent a complete (R0) non-anatomical resection of an incidentally detected solitary hepatocellular carcinoma (HCC) in a non-cirrhotic liver. Six years following the initial R0 non-anatomical resection, intrahepatic recurrence was diagnosed and the patient underwent a second R0 non-anatomical resection. At 12.5 years following the initial resection, a further intrahepatic recurrence was diagnosed, which was once again completely resected by left lateral hepatectomy. This represents one of the longest reported periods between initial resection and HCC recurrence, following repeated R0 resections in the absence of cirrhosis. The appropriate surveillance period and genetic testing protocol for such cases remains to be established.