Pathological serosa and node-based classification accurately predicts gastric cancer recurrence risk and outcome, and determines potential and limitation of a Japanese-style extensive surgery for Western patients: A prospective with quality control 10-year follow-up study

UICC classification accurately predicts overall survival but not recurrence-risk. We report here data of overall and first site-specific recurrence following curative surgery useful for the development of recurrence-oriented preventive target therapies. Patients who underwent resection for gastric cancer were stratified according to curability of surgery [curative (R0) vs non-curative resection], extent of surgery [limited (D1) vs extended (D2) node dissection] and pathological nodal/serosal status. The intent-to-treat principle, log-rank test and Cox regression analysis were used for statistical analysis of time-to-event (recurrence, death) endpoints. Curative resection only produced a chance of cure whereas survival was very poor following non-curative resection (P < 0.0001). For D2 R0 subgroup of patients, a pathological serosa and a node state-based classification into three groups, proved to be of clinical implication. Risk of recurrence after a median follow-up of 92 months was low among patients with both serosa and node-negative cancer (first group; 11%), moderate among those with either serosa or node-positive cancer (second group; 53%) and very high among those with both serosa and node-positive cancer (third group; 83%). In multivariate analysis, the relative risks of recurrence and death from gastric cancer among patients in the second and third groups, as compared to those in the first, were 7.07 (95% CI, 2.36–21.17;P  = 0.0002) and 16.19 (95% CI, 5.76–45.54;P < 0.0001) respectively. First site-specific recurrence analysis revealed: low rate of loco-regional recurrence alone (12%), serosa state determinant factor of the site-recurrence (peritoneal for serosa-positive and haematogenous for serosa-negative cancers) and dramatic increase of all types of recurrence by the presence of nodal metastases. Our findings demonstrate that a pathological serosa- and node-based classification is very simple and predicts accurately site-specific recurrence-risks. Furthermore they reveal that risk of recurrence following curative D2 surgery alone is low for serosa- and node-negative cancers, but very high in serosa- and node-positive cancers suggesting the need for new therapeutic strategies in this subgroup of patients. © 2001 Cancer Research Campaign http://www.bjcancer.co

Barriers and facilitators in implementing a pilot, pragmatic, telemedicine-delivered healthy lifestyle program for obesity management in a rural, academic obesity clinic

Few evidence-based strategies are specifically tailored for disparity populations such as rural adults. Two-way video-conferencing using telemedicine can potentially surmount geographic barriers that impede participation in high-intensity treatment programs offering frequent visits to clinic facilities. We aimed to understand barriers and facilitators of implementing a telemedicine-delivered tertiary-care, rural academic weight-loss program for the management of obesity

Feasibility and acceptability of a rural, pragmatic, telemedicine‐ delivered healthy lifestyle programme

Background: The public health crisis of obesity leads to increasing morbidity that are even more profound in certain populations such as rural adults. Live, two‐way video‐conferencing is a modality that can potentially surmount geographic barriers and staffing shortages. Methods: Patients from the Dartmouth‐Hitchcock Weight and Wellness Center were recruited into a pragmatic, single‐arm, nonrandomized study of a remotely delivered 16‐week evidence‐based healthy lifestyle programme. Patients were provided hardware and appropriate software allowing for remote participation in all sessions, outside of the clinic setting. Our primary outcomes were feasibility and acceptability of the telemedicine intervention, as well as potential effectiveness on anthropometric and functional measures. Results: Of 62 participants approached, we enrolled 37, of which 27 completed at least 75% of the 16‐week programme sessions (27% attrition). Mean age was 46.9 ± 11.6 years (88.9% female), with a mean body mass index of 41.3 ± 7.1 kg/m2 and mean waist circumference of 120.7 ± 16.8 cm. Mean patient participant satisfaction regarding the telemedicine approach was favourable (4.48 ± 0.58 on 1‐5 Likert scale—low to high) and 67.6/75 on standardized questionnaire. Mean weight loss at 16 weeks was 2.22 ± 3.18 kg representing a 2.1% change (P \u3c .001), with a loss in waist circumference of 3.4% (P = .001). Fat mass and visceral fat were significantly lower at 16 weeks (2.9% and 12.5%; both P \u3c .05), with marginal improvement in appendicular skeletal muscle mass (1.7%). In the 30‐second sit‐to‐stand test, a mean improvement of 2.46 stands (P = .005) was observed. Conclusion: A telemedicine‐delivered, intensive weight loss intervention is feasible, acceptable, and potentially effective in rural adults seeking weight loss

Feasibility and acceptability of a technology-based, rural weight management int ervention in older adults with obesity

Background Older adults with obesity residing in rural areas have reduced access to weight management programs. We determined the feasibility, acceptability and preliminary outcomes of an integrated technology-based health promotion intervention in rural-living, older adults using remote monitoring and synchronous video-based technology. Methods A 6-month, non-randomized, non-blinded, single-arm study was conducted from October 2018 to May 2020 at a community-based aging center of adults aged ≥65 years with a body mass index (BMI) ≥30 kg/m2. Weekly dietitian visits focusing on behavior therapy and caloric restriction and twice-weekly physical therapist-led group strength, flexibility and balance training classes were delivered using video-conferencing to participants in their homes. Participants used a Fitbit Alta HR for remote monitoring with data feedback provided by the interventionists. An aerobic activity prescription was provided and monitored. Results Mean age was 72.9±3.9 years (82% female). Baseline anthropometric measures of weight, BMI, and waist circumference were 97.8±16.3 kg, 36.5±5.2 kg/m2, and 115.5±13.0 cm, respectively. A total of 142 participants were screened (n=27 ineligible), and 53 consented. There were nine dropouts (17%). Overall satisfaction with the trial (4.7+ 0.6, scale: 1 (low) to 5 (high)) and with Fitbit (4.2+ 0.9) were high. Fitbit was worn an average of 81.7±19.3% of intervention days. In completers, mean weight loss was 4.6±3.5 kg or 4.7±3.5% (p\u3c 0.001). Physical function measures of 30-s sit-to-stand repetitions increased from 13.5±5.7 to 16.7±5.9 (p\u3c 0.001), 6-min walk improved by 42.0±77.3 m (p=0.005) but no differences were observed in gait speed or grip strength. Subjective measures of late-life function improved (3.4±4.7 points, p\u3c 0.001). Conclusions A technology-based obesity intervention is feasible and acceptable to older adults with obesity and may lead to weight loss and improved physical function. Clinical trial registration Registered on Clinicaltrials.gov #NCT03104205. Registered on April 7, 2017. First participant enrolled on October 1st, 2018

Protein Supplementation May Dampen Positive Effects of Exercise on Glucose Homeostasis: A Pilot Weight Loss Intervention

Background: The role of protein in glucose homeostasis has demonstrated conflicting results. However, little research exists on its impact following weight loss. This study examined the impact of protein supplementation on glucose homeostasis in older adults >65 years with obesity seeking to lose weight. Methods: A 12-week, nonrandomized, parallel group intervention of protein (PG) and nonprotein (NPG) arms for 28 older rural adults (body mass index (BMI) ≥ 30 kg/m2) was conducted at a community aging center. Both groups received twice weekly physical therapist-led group strength training classes. The PG consumed a whey protein supplement three times per week, post-strength training. Primary outcomes included pre/post-fasting glucose, insulin, inflammatory markers, and homeostasis model assessment of insulin resistance (HOMA-IR). Results: Mean age and baseline BMI were 72.9 ± 4.4 years and 37.6 ± 6.9 kg/m2 in the PG and 73.0 ± 6.3 and 36.6 ± 5.5 kg/m2 in the NPG, respectively. Mean weight loss was −3.45 ± 2.86 kg in the PG and −5.79 ± 3.08 kg in the NPG (p < 0.001). There was a smaller decrease in pre- vs. post-fasting glucose levels (PG: −4 mg ± 13.9 vs. NPG: −12.2 ± 25.8 mg/dL; p = 0.10), insulin (−7.92 ± 28.08 vs. −46.7 ± 60.8 pmol/L; p = 0.01), and HOMA-IR (−0.18 ± 0.64 vs. −1.08 ± 1.50; p = 0.02) in the PG compared to the NPG. Conclusions: Protein supplementation during weight loss demonstrated a smaller decrease in insulin resistance compared to the NPG, suggesting protein may potentially mitigate beneficial effects of exercise on glucose homeostasis

Baseline Serum Biomarkers Predict Response to a Weight Loss Intervention in Older Adults with Obesity: A Pilot Study

Caloric restriction and aerobic and resistance exercise are safe and effective lifestyle interventions for achieving weight loss in the obese older population (>65 years) and may improve physical function and quality of life. However, individual responses are heterogeneous. Our goal was to explore the use of untargeted metabolomics to identify metabolic phenotypes associated with achieving weight loss after a multi-component weight loss intervention. Forty-two older adults with obesity (body mass index, BMI, ≥30 kg/m2) participated in a six-month telehealth-based weight loss intervention. Each received weekly dietitian visits and twice-weekly physical therapist-led group strength training classes with a prescription for aerobic exercise. We categorized responders’ weight loss using a 5% loss of initial body weight as a cutoff. Baseline serum samples were analyzed to determine the variable importance to the projection (VIP) of signals that differentiated the responder status of metabolic profiles. Pathway enrichment analysis was conducted in Metaboanalyst. Baseline data did not differ significantly. Weight loss was 7.2 ± 2.5 kg for the 22 responders, and 2.0 ± 2.0 kg for the 20 non-responders. Mummichog pathway enrichment analysis revealed that perturbations were most significant for caffeine and caffeine-related metabolism (p = 0.00028). Caffeine and related metabolites, which were all increased in responders, included 1,3,7-trimethylxanthine (VIP = 2.0, p = 0.033, fold change (FC) = 1.9), theophylline (VIP = 2.0, p = 0.024, FC = 1.8), paraxanthine (VIP = 2.0, p = 0.028, FC = 1.8), 1-methylxanthine (VIP = 1.9, p = 0.023, FC = 2.2), 5-acetylamino-6-amino-3-methyluracil (VIP = 2.2, p = 0.025, FC = 2.2), 1,3-dimethyl uric acid (VIP = 2.1, p = 0.023, FC = 2.3), and 1,7-dimethyl uric acid (VIP = 2.0, p = 0.035, FC = 2.2). Increased levels of phytochemicals and microbiome-related metabolites were also found in responders compared to non-responders. In this pilot weight loss intervention, older adults with obesity and evidence of significant enrichment for caffeine metabolism were more likely to achieve ≥5% weight loss. Further studies are needed to examine these associations in prospective cohorts and larger randomized trials

Effective SLOPE: EffectS of Lifestyle interventions in Older PEople with obesity: a systematic review and network meta-analysis protocol

Introduction Obesity is highly prevalent in older adults aged 65 years or older. Different lifestyle interventions (diet, exercise, self-management) are available but benefits and harms have not been fully quantified comparing all available health promotion interventions. Special consideration must be given to functional outcomes and possible adverse effects (loss of muscle and bone mass, hypoglycaemia) of weight loss interventions in this age group. The objective of this study is to synthesise the evidence regarding the effects of different types and modalities of lifestyle interventions, or their combinations, on physical function and obesity-related outcomes such as body composition in older adults with obesity. Methods and analyses Six databases (Medline, Embase, Cochrane Central Register of Controlled Trials, Cumulated Index to Nursing and Allied Health Literature (CINAHL), Psychinfo and Web of Science) and two trial registries (Clinicaltrials.gov and the WHO International Clinical Trials Registry Platform) will be searched for randomised controlled trials of lifestyle interventions in older adults with obesity. Screening (title/abstract and full-text) and data extraction of references as well as assessment of risk of bias and rating of the certainty of evidence (Grading of Recommendations, Assessment, Development and Evaluation for network meta-analyses) will be performed by two reviewers independently. Frequentist random-effects network meta-analyses will be conducted to determine the pooled effects from each intervention. Ethics and dissemination We will submit our findings to peer-reviewed journals and present at national and international conferences as well as in scientific medical societies. Patient-targeted dissemination will involve local and national advocate groups. PROSPERO registration number CRD42019147286

Sarcopenic obesity research perspectives outlined by the sarcopenic obesity global leadership initiative (SOGLI) – Proceedings from the SOGLI consortium meeting in rome November 2022

The European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Association for the Study of Obesity (EASO) launched the Sarcopenic Obesity Global Leadership Initiative (SOGLI) to reach expert consensus on a definition and diagnostic criteria for Sarcopenic Obesity (SO). The present paper describes the proceeding of the Sarcopenic Obesity Global Leadership Initiative (SOGLI) meeting that was held on November 25th and 26th, 2022 in Rome, Italy. This consortium involved the participation of 50 researchers from different geographic regions and countries. The document outlines an agenda advocated by the SOGLI expert panel regarding the pathophysiology, screening, diagnosis, staging and treatment of SO that needs to be prioritized for future research in the field

Obesity resistant mechanisms in the Lean polygenic mouse model as indicated by liver transcriptome and expression of selected genes in skeletal muscle

<p>Abstract</p> <p>Background</p> <p>Divergently selected Lean and Fat mouse lines represent unique models for a polygenic form of resistance and susceptibility to obesity development. Previous research on these lines focused mainly on obesity-susceptible factors in the Fat line. This study aimed to examine the molecular basis of obesity-resistant mechanisms in the Lean line by analyzing various fat depots and organs, the liver transcriptome of selected metabolic pathways, plasma and lipid homeostasis and expression of selected skeletal muscle genes.</p> <p>Results</p> <p>Expression profiling using our custom Steroltalk v2 microarray demonstrated that Lean mice exhibit a higher hepatic expression of cholesterol biosynthesis genes compared to the Fat line, although this was not reflected in elevation of total plasma or liver cholesterol. However, FPLC analysis showed that protective HDL cholesterol was elevated in Lean mice. A significant difference between the strains was also found in bile acid metabolism. Lean mice had a higher expression of <it>Cyp8b1</it>, a regulatory enzyme of bile acid synthesis, and the <it>Abcb11 </it>bile acid transporter gene responsible for export of acids to the bile. Additionally, a higher content of blood circulating bile acids was observed in Lean mice. Elevated HDL and upregulation of some bile acids synthesis and transport genes suggests enhanced reverse cholesterol transport in the Lean line - the flux of cholesterol out of the body is higher which is compensated by upregulation of endogenous cholesterol biosynthesis. Increased skeletal muscle <it>Il6 </it>and <it>Dio2 </it>mRNA levels as well as increased activity of muscle succinic acid dehydrogenase (SDH) in the Lean mice demonstrates for the first time that changes in muscle energy metabolism play important role in the Lean line phenotype determination and corroborate our previous findings of increased physical activity and thermogenesis in this line. Finally, differential expression of <it>Abcb11 </it>and <it>Dio2 </it>identifies novel strong positional candidate genes as they map within the quantitative trait loci (QTL) regions detected previously in crosses between the Lean and Fat mice.</p> <p>Conclusion</p> <p>We identified novel candidate molecular targets and metabolic changes which can at least in part explain resistance to obesity development in the Lean line. The major difference between the Lean and Fat mice was in increased liver cholesterol biosynthesis gene mRNA expression, bile acid metabolism and changes in selected muscle genes' expression in the Lean line. The liver <it>Abcb11 </it>and muscle <it>Dio2 </it>were identified as novel positional candidate genes to explain part of the phenotypic difference between the Lean and Fat lines.</p