Kellogg, Todd A.

Background: Gastrojejunal (GJ) anastomotic stenosis is a well-described complication after Roux-en-Y gastric bypass (RYGB); however, its impact on weight loss outcomes is not well elucidated. Methods: We performed a retrospective cohort study of adult patients who underwent RYGB at our institution between 2008 and 2020. Propensity score matching was used to match 30 patients who developed GJ stenosis within the first 30 days post-RYGB with 120 control patients who did not develop this outcome. Short and long-term complications and mean percentage of total body weight loss (TWL) were recorded at 3 months, 6 months, 1 year, 2 years, 3 to 5 years, and 5 to 10 years postoperatively. Hierarchical linear regression modeling was used to analyze the association between early GJ stenosis and the mean percentage of TWL. Results: Patients who developed early GJ stenosis had a 13.6% increase in the mean percentage of TWL when compared with controls in the hierarchical linear model [P < 0.001 (95% CI: 5.7; 21.5)]. These patients were also more likely to present to an intravenous infusion center (70% vs 4%; P < 0.01), require readmission within 30 days (16.7% vs 2.5%; P < 0.01), and/or develop an internal hernia (23.3% vs 5.0%) postoperatively. Conclusions: Patients who develop early GJ stenosis after RYGB have a greater degree of long-term weight loss compared with patients who do not develop this complication. Although our findings support the key contribution that restrictive mechanisms play in maintaining weight loss after RYGB, GJ stenosis remains a complication associated with significant morbidity.

BACKGROUND: The MBSAQIP has been used to evaluate risk and create risk models. Previous studies have determined what complications matter most. STUDY DESIGN: This study was a registry-based analysis of patients who underwent laparoscopic Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) between January 1, 2015, and December 31, 2019, at centers participating in MBSAQIP. Cases were identified using Current Procedural Terminology. Patients less than 18 years old were excluded. A chi-square test was used to assess differences in the prevalence of complications and effects across years. Using a multivariable Poisson regression model with a link log and robust estimation, prevalence ratio estimates and 95% CI were obtained. RESULTS: A total of 690,770 observations met the inclusion criteria. Mean (SD) age was 44.5 (±12.0) years, and mean (SD) BMI was 45.2 kg/m2 (±7.9). SG cases accounted for 73.45% of all observations. There was a significant relative reduction in readmissions, end-organ dysfunction, and all-cause mortality from 2015 to 2019 in the SG subgroup. There were also noticeable reductions in 30-day readmission, ICU admission, and end-organ dysfunction in the RYGB subgroup. For complications, bleeding, postoperative pneumonia, and stroke were significantly decreased in the RYGB subgroup, but only bleeding was significantly decreased in the SG subgroup during the 5-year study period. CONCLUSIONS: There has been a continuous improvement in several (but not all) outcomes through the years that the MBSAQIP has been collecting data. Different outcomes were reduced between the SG and RYGB subgroups, and the decrease in all-cause mortality was only noted in the SG subgroup.

Background: Bariatric surgery is the most effective treatment for weight loss and obesity-related comorbidity resolution. However, bariatric surgery is not readily offered in specific populations due to the lack of data assessing its feasibility. This study intends to evaluate bariatric surgery in patients with an existing ostomy. Methods: We conducted a retrospective case series to assess the safety of Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) in patients with an end ileostomy or colostomy. Patient demographics, including obesity-related comorbidities, overall health status (American Society of Anesthesiologists score), and short-term complications (up to 30 days postoperatively), were analyzed. Results: Six patients were included. The mean age was 58 years, and the mean preoperative body mass index was 41.6. Three patients had a colostomy, and three had an ileostomy. The mean time of ostomy before surgery was 11 years. Two ostomies were due to trauma, two due to inflammatory bowel disease, one due to cancer, and one due to scleroderma. Mean postoperative follow-up was 23 months. No patient had increased ostomy output or infusion center visit. One patient had an ED visit, one had a short-term complication, and one had SG conversion to RYGB. Conclusions: Bariatric surgery is technically feasible in selected patients with ileostomy/colostomy with a reasonable short-term safety profile.

While the safety of video follow-up in bariatric surgery is established, patients’ perception of telemedicine visits remained unknown. A randomized clinical trial evaluating patients’ perception of video postoperative follow-up (F/U) visits was conducted in the pre COVID-19 era. 24 patients were randomized in the preoperative clinic to receive either in-person or video F/U, and then surveyed about their experience and preference. The majority reported that if they had to do it over, they would prefer a video visit. Among those who received video visits, 11/12 reported that the lack of physical contact was acceptable. 82% of the video group expressed that their visit was better or as good as an in-person visit, while 9% were not sure, and 9% reported that video was worse. This finding suggests that postoperative video follow-up visits are acceptable among bariatric surgery patients and should be offered as an alternative to traditional visits.

ObjectiveThis study tested whether substrate concentrations or fatty acid storage proteins predict storage of endogenous lipids in visceral adipose tissue (VAT) and upper body subcutaneous adipose tissue (UBSQ) fat.MethodsThe day prior to surgery, 25 patients undergoing bariatric procedures received an infusion of autologous [1‐14C]triolein‐labeled very low‐density lipoprotein (VLDL) particles, and during surgery, they received a continuous [U‐13C]palmitate infusion/bolus [9,10‐3H]palmitate tracer. VAT and UBSQ fat were collected to measure VLDL‐triglyceride (TG) storage, direct free fatty acid (FFA) storage rates, CD36 content, lipoprotein lipase (LPL), acyl‐CoA synthetase, diacylglycerol acetyl‐transferase, and glycerol‐3‐phosphate acyltransferase activities.ResultsStorage of VLDL‐TG and FFA‐palmitate in UBSQ and VAT was not different. Plasma palmitate concentrations correlated with palmitate storage rates in UBSQ and VAT (r = 0.46, P = 0.02 and r = 0.46, P = 0.02, respectively). In VAT, VLDL‐TG storage was correlated with VLDL concentrations (r = 0.53, P < 0.009) and LPL (r = 0.42, P < 0.05). In UBSQ, VLDL‐TG storage was correlated with LPL (r = 0.42, P < 0.05). CD36, acyl‐CoA synthetase, glycerol‐3‐phosphate acyltransferase, and diacylglycerol acetyl‐transferase were not correlated with VLDL‐TG or palmitate storage.ConclusionsAdipose storage of VLDL‐TG is predicted by VLDL‐TG concentrations and LPL; FFA concentrations predict direct adipose tissue FFA storage rates.

Mesenchymal stem/stromal cells (MSCs) facilitate repair in experimental diabetic kidney disease (DKD). However, the hyperglycemic and uremic milieu may diminish regenerative capacity of patient-derived therapy. We hypothesized that DKD reduces human MSC paracrine function. Adipose-derived MSC from 38 participants with DKD and 16 control subjects were assessed for cell surface markers, trilineage differentiation, RNA sequencing (RNA-seq), in vitro function (coculture or conditioned medium experiments with T cells and human kidney cells [HK-2]), secretome profile, and cellular senescence abundance. The direction of association between MSC function and patient characteristics were also tested. RNA-seq analysis identified 353 differentially expressed genes and downregulation of several immunomodulatory genes/pathways in DKD-MSC versus Control-MSC. DKD-MSC phenotype, differentiation, and tube formation capacity were preserved, but migration was reduced. DKD-MSC with and without interferon-γ priming inhibited T-cell proliferation greater than Control-MSC. DKD-MSC medium contained higher levels of anti-inflammatory cytokines (indoleamine 2,3-deoxygenase 1 and prostaglandin-E2) and prorepair factors (hepatocyte growth factor and stromal cell–derived factor 1) but lower IL-6 versus control-MSC medium. DKD-MSC medium protected high glucose plus transforming growth factor-β–exposed HK-2 cells by reducing apoptotic, fibrotic, and inflammatory marker expression. Few DKD-MSC functions were affected by patient characteristics, including age, sex, BMI, hemoglobin A1c, kidney function, and urine albumin excretion. However, senescence-associated β-galactosidase activity was lower in DKD-MSC from participants on metformin therapy. Therefore, while DKD altered the transcriptome and migratory function of culture-expanded MSCs, DKD-MSC functionality, trophic factor secretion, and immunomodulatory activities contributing to repair remained intact. These observations support testing of patient-derived MSC therapy and may inform preconditioning regimens in DKD clinical trials.

AbstractThe global prevalence of nonalcoholic fatty liver disease (NAFLD) is estimated to be 25% and continues to rise worldwide in the setting of the obesity epidemic. This increase is especially concerning because NAFLD is often a progressive disease that can be associated with significant complications such as liver cirrhosis, hepatocellular carcinoma, and an increase in liver‐related and overall mortality. Because of the devastating complications and comorbidities, NAFLD is a very costly disease for the healthcare system, with estimated annual direct medical costs exceeding $100 billion in the United States alone. Given this progressive course, it is imperative to make the diagnosis in patients with risk factors (metabolic syndrome, weight gain, and insulin resistance/diabetes). Once the diagnosis is made, the focus should shift to treatment and monitoring for the development of associated complications. Given that currently no pharmaceutical intervention is approved for the treatment of NAFLD, focus shifts instead to mitigation of risk factors through avoidance of foods that are rich in red meat, trans fats, refined carbohydrates, and high‐fructose corn syrup; are low fiber; and have high energy density. The landmark of treatment, however, continues to be weight loss and improvement of insulin resistance, often through a multimodality approach. The current manuscript reviews the clinical phenotypes of NAFLD, its risk factors, and pathogenesis, as well as treatment options including lifestyle modifications and dietary interventions, medical therapies, endoscopic bariatric interventions, and bariatric surgery.

Disease monitoring in nonalcoholic steatohepatitis (NASH) is limited by absence of noninvasive biomarkers of disease regression or progression. We aimed to examine the role of multiparametric three‐dimensional magnetic resonance elastography (3D‐MRE) and magnetic resonance imaging proton density fat fraction (MRI‐PDFF) in the detection of NASH regression after interventions. This is a single‐center prospective clinical trial of 40 patients who underwent bariatric surgery. Imaging and liver biopsies were obtained at baseline and 1 year after surgery. The imaging protocol consisted of multifrequency 3D‐MRE to determine the shear stiffness at 60 Hz and damping ratio at 40 Hz, and MRI‐PDFF to measure the fat fraction. A logistic regression model including these three parameters was previously found to correlate with NASH. We assessed the model performance in the detection of NASH resolution after surgery by comparing the image‐predicted change in NAFLD activity score (delta NAS) to the histologic changes. A total of 38 patients (median age 43, 87% female, 30 of 38 with NAS ≥ 1, and 13 of 38 with NASH) had complete data at 1 year. The NAS decreased in all subjects with NAS ≥ 1 at index biopsy, and NASH resolved in all 13. There was a strong correlation between the predicted delta NAS by imaging and the delta NAS by histology (r = 0.73, P < 0.001). The strength of correlation between histology and the predicted delta NAS using single conventional parameters, such as the fat fraction by MRI‐PDFF or shear stiffness at 60 Hz by MRE, was r = 0.69 (P < 0.001) and r = 0.43 (P = 0.009), respectively. Conclusion: Multiparametric 3D‐MRE and MRI‐PDFF can detect histologic changes of NASH resolution after bariatric surgery. Studies in a nonbariatric setting are needed to confirm the performance as a composite noninvasive biomarker for longitudinal NASH monitoring.

Macrophage-based immune dysregulation plays a critical role in development of delayed gastric emptying in diabetic mice. Loss of anti-inflammatory macrophages and increased expression of genes associated with pro-inflammatory macrophages has been reported in full-thickness gastric biopsies from gastroparesis patients. We aimed to determine broader protein expression (proteomics) and protein-based signaling pathways in gastric biopsies of diabetic (DG) and idiopathic gastroparesis (IG) patients. Additionally, we determined correlations between protein expressions, gastric emptying, and symptoms. Full-thickness gastric antrum biopsies were obtained from nine DG patients, seven IG patients, and five nondiabetic controls. Aptamer-based SomaLogic tissue scan that quantitatively identifies 1,305 human proteins was used. Protein fold changes were computed, and differential expressions were calculated using Limma. Ingenuity pathway analysis and correlations were carried out. Multiple-testing corrected P < 0.05 was considered statistically significant. Seventy-three proteins were differentially expressed in DG, 132 proteins were differentially expressed in IG, and 40 proteins were common to DG and IG. In both DG and IG, “Role of Macrophages, Fibroblasts and Endothelial Cells” was the most statistically significant altered pathway [DG false discovery rate (FDR) = 7.9 × 10−9; IG FDR = 6.3 × 10−12]. In DG, properdin expression correlated with GCSI bloating ( r = −0.99, FDR = 0.02) and expressions of prostaglandin G/H synthase 2, protein kinase C-ζ type, and complement C2 correlated with 4 h gastric retention ( r = −0.97, FDR = 0.03 for all). No correlations were found between proteins and symptoms or gastric emptying in IG. Protein expression changes suggest a central role of macrophage-driven immune dysregulation in gastroparesis, specifically, complement activation in diabetic gastroparesis. NEW & NOTEWORTHY This study uses SOMAscan, a novel proteomics assay for determination of altered proteins and associated molecular pathways in human gastroparesis. Seventy-three proteins were changed in diabetic gastroparesis, 132 in idiopathic gastroparesis compared with controls. Forty proteins were common in both. Macrophage-based immune dysregulation pathway was most significantly affected in both diabetic and idiopathic gastroparesis. Proteins involved in the complement and prostaglandin synthesis pathway were associated with symptoms and gastric emptying delay in diabetic gastroparesis.