Cellular and physiological circadian mechanisms drive diurnal cell proliferation and expansion of white adipose tissue.

Hyperplastic expansion of white adipose tissue (WAT) relies in part on the proliferation of adipocyte precursor cells residing in the stromal vascular cell fraction (SVF) of WAT. This study reveals a circadian clock- and feeding-induced diurnal pattern of cell proliferation in the SVF of visceral and subcutaneous WAT in vivo, with higher proliferation of visceral adipocyte progenitor cells subsequent to feeding in lean mice. Fasting or loss of rhythmic feeding eliminates this diurnal proliferation, while high fat feeding or genetic disruption of the molecular circadian clock modifies the temporal expression of proliferation genes and impinges on diurnal SVF proliferation in eWAT. Surprisingly, high fat diet reversal, sufficient to reverse elevated SVF proliferation in eWAT, was insufficient in restoring diurnal patterns of SVF proliferation, suggesting that high fat diet induces a sustained disruption of the adipose circadian clock. In conclusion, the circadian clock and feeding simultaneously impart dynamic, regulatory control of adipocyte progenitor proliferation, which may be a critical determinant of adipose tissue expansion and health over time.

Thromboelastography-Based Profiling of Coagulation Status in Patients Undergoing Bariatric Surgery: Analysis of 422 Patients.

INTRODUCTION/PURPOSE: Some clinical indicators suggest hypercoagulability/hyperaggregability in patients with morbid obesity. Thromboelastography (TEG®) has been used to profile coagulation status in surgical patients. We aimed to assess coagulation profiles in patients with morbid obesity undergoing bariatric surgery by correlating demographic and patient characteristics to pre-operative TEG® values. MATERIALS AND METHODS: Pre-operative TEG® values from 422 patients undergoing bariatric surgery were evaluated. TEG® results were analyzed by gender, use of medications known to alter the coagulation profile, and body mass index (BMI). RESULTS: Patients have a mean of 45.03 ± 11.8 years, female (76.3%), and with a mean BMI of 42 kg/m 1. The overall coagulation profile of female patients was significantly different from males, even in the sub-cohort without use of medications known to alter coagulation. The majority of patients (94%) with a G value > 15 dynes/cm 1 (clot strength) were female. In females, there was no association between BMI and TEG® values; however, in men, there was a statistically significant difference in TEG® values for those with BMI < 40 kg/m 1 compared to those with BMI > 50 kg/m2. CONCLUSIONS: TEG®-based analysis of coagulation profiles offers unique insights. Compared to laboratory normal values (R time, angle, maximal amplitude, and G values), patients with morbid obesity may have a tendency for hypercoagulability/hyperaggregability, with mean values at the higher limit. A significant hypercoagulable difference in TEG® values was identified in female as compared to male patients. Male patients with a BMI greater than 50 kg/m2 were also found to be increasingly hypercoagulable.

Outcomes of primary versus revisional robotically assisted laparoscopic Roux-en-Y gastric bypass: a multicenter analysis of ten-year experience.

BACKGROUND: Postoperative morbidity after laparoscopic bariatric surgery is considered higher for patients undergoing revisional versus primary procedures. The objective of this retrospective cohort study was to compare outcomes between patients undergoing primary versus revisional robotically assisted laparoscopic (RAL) Roux-en-Y gastric bypass (RYGB). METHODS: Data of all patients who underwent RAL primary and revisional RYGB between 2009 and 2019 at two accredited, high-volume bariatric surgery centers-the Memorial Hermann - Texas Medical Center, Houston, TX, and the Tower Health, Reading Hospital, Reading, PA, were analyzed. Primary outcomes were early (< 30 days) and overall postoperative complications. Secondary outcomes included intraoperative complications, operative times, conversions to laparotomy, length of hospital stay, early (< 30 days) postoperative readmissions and deaths. RESULTS: Data of 1072 patients were analyzed, including 806 primary and 266 revisional RAL RYGB procedures. Longer operative times (203 versus 154 min, P < 0.001), increased number of readmissions for oral intolerance (10.5% versus 6.7%, P = 0.046) and higher rate of gastrojejunal stricture (6.4% versus 2.7%, P = 0.013) were found in the revisional group. Gastrointestinal leak rates were 0.2% for the primary versus 1.1% for the revisional group (P = 0.101). Early (< 30 days) reoperations rates were 2.2% for the primary versus 1.1% for the revisional group (P = 0.318). There were no statistically significant differences between groups in overall and severe complication rates. CONCLUSION: Patients undergoing RAL primary and revisional RYGB had comparable overall outcomes, with a non-significant higher early complication rate in the revisional group. Despite the study being underpowered to detect differences in specific complication rates, the morbidity seen in the revisional RYGB group remains markedly below literature reports of revisional laparoscopic RYGB and might suggest a benefit of robotic assistance. Further prospective studies are needed to confirm these results.

Age-associated telomere attrition in adipocyte progenitors predisposes to metabolic disease.

White and beige adipocytes in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) are maintained by proliferation and differentiation of adipose progenitor cells (APCs). Here we use mice with tissue-specific telomerase reverse transcriptase (TERT) gene knockout (KO), which undergo premature telomere shortening and proliferative senescence in APCs, to investigate the effect of over-nutrition on APC exhaustion and metabolic dysfunction. We find that TERT KO in the Pdgfra+ cell lineage results in adipocyte hypertrophy, inflammation and fibrosis in SAT, while TERT KO in the Pdgfrb+ lineage leads to adipocyte hypertrophy in both SAT and VAT. Systemic insulin resistance is observed in both KO models and is aggravated by a high-fat diet. Analysis of human biopsies demonstrates that telomere shortening in SAT is associated with metabolic disease progression after bariatric surgery. Our data indicate that over-nutrition can promote APC senescence and provide a mechanistic link between ageing, obesity and diabetes.

Trocar site closure with a novel anchor-based (neoClose®) system versus standard suture closure: a prospective randomized controlled trial.

BACKGROUND: Patients with obesity have a higher risk of trocar site hernia. The objective of the present study was to compare a standard suture passer versus the neoClose® device for port site fascial closure in patients with obesity undergoing laparoscopic bariatric surgery. METHODS: This is a randomized, controlled trial with two parallel arms. Thirty five patients with BMI ≥ 35 kg/m2 and undergoing laparoscopic sleeve gastrectomy or Roux-en-Y gastric bypass were randomized to each group. Port site fascial closure for trocars ≥ 10 mm was performed with the neoClose® device in the study group and the standard suture passer in the control group. Primary outcomes were time required to complete closure and intensity of postoperative pain at the fascial closure sites. Secondary outcomes were intraabdominal needle depth and incidence of trocar site hernia. RESULTS: The use of the neoClose® device resulted in shorter closure times (20.2 vs 30.0 s, p = 0.0002), less pain (0.3 vs 0.9, p = 0.002) at port closure sites, and decreased needle depth (3.3 cm vs 5.2 cm, p < 0.0001) compared to the standard suture passer. There was no trocar site hernia at the one-year follow-up in either group. CONCLUSIONS: Use of the neoClose® device resulted in faster fascial closure times, decreased intraoperative needle depth, and decreased postoperative abdominal pain at 1 week as compared to the standard suture passer. These data need to be confirmed on larger cohorts of patients with longer follow-up.

Correction to: Trocar site closure with a novel anchor-based (neoClose®) system versus standard suture closure: a prospective randomized controlled trial.

After careful review, the authors have noticed the following mistakes in the article entitled "Trocar site closure with a novel anchor based (neoClose®) system versus standard suture closure: A prospective randomized controlled trial": - Correct closure times are 19.9 seconds (SD 9.9) for the study group and 31.0 seconds (SD 20.1) for the control group (initial incorrect values were 20.2 seconds (SD 10.1) and 30 seconds (SD 19.1) respectively). The new correct P-value is <0.0001 (initial incorrect P-value was 0.0002). - Correct maximal needle depth values are 3.2 cm (SD 0.93) for the study group and 4.9 cm (SD 1.97) for the control group (initial incorrect values were 3.3 cm (SD 0.9) and 5.2 cm (SD 1.6) respectively). P-value remains unchanged at <0.0001. For these two outcomes, some values of control group patients were mistakenly included in the study group. These errors only marginally affected the mean and standard deviation values. Statistical significance of the results was not affected and the conclusions of the study remain unchanged.

Safety of robotic assisted laparoscopic recurrent paraesophageal hernia repair: insights from a large single institution experience.

BACKGROUND: Laparoscopic repair of recurrent as opposed to primary paraesophageal hernias (PEHs) are historically associated with increased peri-operative complication rates, worsened outcomes, and increased conversion rates. The robotic platform may aid surgeons in these complex revision procedures. The aim of this study was to compare the outcomes of patients undergoing robotic assisted laparoscopic (RAL) repair of recurrent as opposed to primary PEHs. METHODS: Patients undergoing RAL primary and recurrent PEH repairs from 2009 to 2017 at a single institution were reviewed. Demographics, use of mesh, estimated blood loss, intra-operative complications, conversion rates, operative time, rates of esophageal/gastric injury, hospital length of stay, re-admission/re-operation rates, recurrence, dysphagia, gas bloat, and pre- and post-operative proton pump inhibitor (PPI) use were analyzed. Analysis was accomplished using Chi-square test/Fischer's exact test for categorical variables and the Mann-Whitney U test for continuous variables. RESULTS: There were 298 patients who underwent RAL PEH repairs (247 primary, 51 recurrent). They were followed for a median (interquartile range) of 120 (44, 470) days. There were no significant differences in baseline demographics between groups. Patients in the recurrent PEH group had longer operative times, increased use of mesh, and increased length of hospital stay. They were also less likely to undergo fundoplication. There were no significant differences in estimated blood loss, incidence of intra-operative complications, re-admission rates, incidence of post-operative dysphagia and gas bloat, and incidence of post-operative PPI use. There were no conversions to open operative intervention or gastric/esophageal injury/leaks. CONCLUSIONS: Although repair of recurrent PEHs are historically associated with worse outcomes, in this series, RAL recurrent PEH repairs have similar peri-operative and post-operative outcomes as compared to primary PEH repairs. Whether this is secondary to the potential advantages afforded by the robotic platform deserves further study.

Endoscopic Sleeve Gastroplasty (ESG) Is a Reproducible and Effective Endoscopic Bariatric Therapy Suitable for Widespread Clinical Adoption: a Large, International Multicenter Study.

OBJECTIVE: Endoscopic sleeve gastroplasty (ESG), an incisionless endoscopic bariatric procedure, has shown impressive results in case series. This study examines the reproducibility, efficacy, and safety in three centers across two countries, and identifies key determinants for procedural success. DESIGN: Patients who underwent ESG between February 2016 and May 2017 at one of three centers (Australia and USA) were retrospectively analyzed. All procedures were performed on an outpatient basis using the Apollo OverStitch device (Apollo Endosurgery, Austin, TX). Primary outcomes included absolute weight loss (ΔWeight, kg), change in body mass index (∆BMI, in kg/m2), total body weight loss (TBWL, %), excess weight loss (EWL, in %), and immediate and delayed adverse events. RESULTS: In total, 112 consecutive patients (male 31%, age 45.1 ± 11.7 years, baseline BMI 37.9 ± 6.7 kg/m2) underwent ESG. At 1, 3, and 6 months, Δweight was 9.0 ± 4.6 kg (TBWL 8.4 ± 4.1%), 12.9 ± 6.4 kg (TBWL 11.9 ± 4.5%), and 16.4 ± 10.7 kg (TBWL 14.9 ± 6.1%), respectively. The proportion of patients who attained greater than 10% TBWL and 25% EWL was 62.2 and 78.0% at 3 months post-ESG and 81.0 and 86.5% at 6 months post-ESG. Weight loss was similar between the three centers. Multivariable analysis showed that male sex, greater baseline body weight, and lack of prior endoscopic bariatric therapy were predictors of greater Δweight at 6 months. Three (2.7%) severe adverse events were observed. CONCLUSIONS: ESG is an effective, reproducible, and safe weight loss therapy that is suitable for widespread clinical adoption.