Clusterin is a newly identified adipokine associated with metabolic dysfunction, yet its postoperative dynamics and relationship to clinical outcomes after metabolic and bariatric surgery (MBS) remain unclear. This study aimed to investigate the changes of clusterin levels following MBS, evaluates its association with weight loss and type 2 diabetes (T2D) remission, and explore the underlying biological mechanisms. In this 1-year retrospective cohort study, 75 patients with obesity and T2D (60

To the Editor: Obesity and type 2 diabetes (T2D) present significant health issues in China. Despite generally having lower body mass index (BMI) thresholds than Western populations, Chinese individuals often experience higher rates of central obesity, leading to increased metabolic risks even at lower BMI levels. The prevalence of T2D among adults in China is estimated to be 11.2%. Traditional treatments, including lifestyle interventions and medications, often fail to achieve sustained weight loss and effective glycemic control in the long term in patients with obesity and T2D. This prospective multicenter observational study aimed to evaluate the 2-year and 5-year treatment effects of laparoscopic Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on T2D patients in China (Clinical Trials identifier: NCT02217943). All subjects from six high-volume tertiary hospitals were recruited between August 2014 and January 2016 [Supplementary Table 1, https://links.lww.com/CM9/C282]. The study protocol was reviewed and approved by the Independent Ethics Committee or the Institutional Review Committee at each center (Ethical approval number of the leading research institution is 2014-32 [Supplementary Material 1, https://links.lww.com/CM9/C282]), and all subjects provided written informed consent before enrollment. Participants were between 20 years old and 60 years old, with a BMI ranging from 28 kg/m2 to 50 kg/m2 and a diagnosis of T2D for at least six months. Subjects were required to have a C-peptide level greater than 1 ng/mL. Exclusions also applied to individuals with certain medical conditions [Supplementary Material 2, https://links.lww.com/CM9/C282]. At baseline, comprehensive data on demographics, medical history, physical exams, and various laboratory tests were collected. Participants underwent either RYGB or SG. The choice of procedure was determined by the attending surgeons. Outpatient follow-up visits were scheduled at 1-month, 3-, 6-, 12-, 24-, 36-, 48-, and 60-months post-surgery and focused on evaluating subjects' glycemic control, weight loss, and other health metrics. Safety was documented through investigator-observed and subject-reported adverse events (AEs). The outcome of T2D status, defined by the American Society for Metabolic and Bariatric Surgery (ASMBS), was evaluated at 2 years and 5 years. T2D status was classified as complete remission, partial remission, improvement, no change, or recurrence using a composite metric of glycemic control combining HbA1c and FPG (see definition in Supplementary Material 3, https://links.lww.com/CM9/C282). The percentage of subjects achieving HbA1c <7.0% regardless of medication usage, changes in body weight, BMI, blood pressure, lipid profile, and liver enzymes were also evaluated. Predefined procedure-related complications were recorded (see definition in Supplementary Material 4, https://links.lww.com/CM9/C282). The full analysis set was used as the primary analysis set and safety set. The number and percentage of subjects achieving each of the five components of the composite measure of glycemic control were summarized, and 95% confidence intervals (CIs) were provided using the Clopper–Pearson method. The change from baseline for HbA1c and cardiometabolic markers were summarized at each postoperative measurement time point, and 95% CIs were provided using the t distribution. No adjustments for covariates were performed for outcome analysis. All analyses were performed using SAS 9.4 (SAS Institute Inc. Cary, NC, USA). A two-sided P <0.05 was considered statistically significant. A total of 101 subjects were enrolled (76 in RYGB and 25 in SG). The mean age was 37.1 ± 9.7 years and 52.5% were women. The mean baseline BMI was 35.1 ± 5.2 kg/m2 and the mean baseline HbA1c was 8.1 ± 1.7%. Baseline clinical characteristics are summarized in Supplementary Table 2, https://links.lww.com/CM9/C282. No subject switched to open surgery. A total of 79 subjects (78.2%, 79/101; 62 RYGB, 17 SG) completed the 2-year follow-up, while 63 subjects (62.4%; 63/101; 51 RYGB, 12 SG) completed the 5-year follow-up. The T2D status of these subjects are presented in Figure 1A. Bivariate analyses comparing subjects with and without complete or partial remission showed that subjects without complete or partial remission had higher mean (Standard Deviation, SD) FPG at baseline mean (Standard Deviation, SD) (9.8 [3.6] mmol/L vs. 8.3 [2.4] mmol/L; P = 0.0432) and a longer duration of T2D (5.0 [2.8] years vs. 3.1 [2.4] years; P <0.05).Figure 1: Five-year outcomes of glycemic control and weight loss after metabolic surgery (RYGB, SG) in Chinese obese population with T2D. (A) The percentage of subjects achieving each of the five components of the composite measure of glycemic control (definition in Supplementary Material 2,https://links.lww.com/CM9/C282) was summarized for each treatment group (RYGB, SG, Total) at two and five years after bariatric/metabolic surgery. (B) Mean BMI and TWL% in the RYGB and SG groups over a 60-months period compared with baseline metric. BMI: Body mass index; RYGB: Roux-en-Y gastric bypass; SG: Sleeve gastrectomy; TWL: Total weight loss; T2D: Type 2 diabetes. (Note: Denominator and percentages are based on subjects with non-missing data)HbA1c decreased rapidly within the first three months after surgery. The percentages of subjects with HbA1c <7.0% regardless of medication status were 93.3% (91.5% for RYGB and 93.8% for SG) at 2 years and 78.3% (78.0% for RYGB and 80.0% for SG) at 5 years [Supplementary Figure 1, https://links.lww.com/CM9/C282]. Improvement in glycemic control was paralleled by an improvement in homeostasis model assessment of insulin resistance (HOMA-IR) [Supplementary Table 2, https://links.lww.com/CM9/C282]. The percentage of subjects receiving oral anti-hyperglycemic medication and/or insulin decreased rapidly after bariatric/metabolic surgery, although there was a slight rebound in medication use over time [Supplementary Figure 2, https://links.lww.com/CM9/C282]. Significant reductions occurred in body weight and mean BMI at 2 years (total weight loss [TWL%] −22.8%, −22.6% for RYGB and −23.5% for SG; BMI −7.9 ± 3.6, −7.9 ± 3.8 kg/m2 for RYGB and −8.1 ± 2.3 kg/m2 for SG; all P <0.001) and at 5 years (TWL% −20.8%, −20.6% for RYGB and −21.8% for SG; BMI −7.2 ± 2.9, −7.1 ± 3.1 kg/m2 for RYGB and −7.7 ± 2.1 kg/m2 for SG; all P <0.001) [Figure 1B]. Hypertension, dyslipidemia, and elevated ALT, AST, and GGT levels improved from baseline to 5 years in both RYGB and SG, consistent with previous studies.[1] Common AEs included deficiencies in iron (49.5%, 50/101), vitamin D (34.7%, 35/101), and vitamin B12 (32.7%, 33/101), along with incision site pain (26.7%, 27/101), anemia (25.7%, 26/101), abdominal pain (17.8%, 18/101), and vomiting (13.9%, 14/101) [Supplementary Table 3, https://links.lww.com/CM9/C282]. Procedure-related AEs and serious adverse events (SAEs) classified according to the Clavien-Dindo (CD) classification of surgical complications are summarized in Supplementary Table 4, https://links.lww.com/CM9/C282. Most AEs were classified as Grade I (overall 77%, 341/443; RYGB 76.3%, 277/363; and SG 80%, 64/80) or II (overall 21.4%, 95/443; RYGB 21.8%, 79/363; and SG 20%, 16/80) according to the Clavien–Dindo classification of surgical complications. SAEs were reported in 10.5% (8/76) of the RYGB group over five years (four gastrointestinal disorders, two anemia, and two metabolism and nutrition disorders), but in none of the SG group [Supplementary Table 4, https://links.lww.com/CM9/C282]. This study demonstrates that both RYGB and SG have substantial long-term benefits for glycemic control and weight loss in Chinese subjects with T2D. Two previous 5-year studies[2,3] evaluating metabolic surgery for T2D subjects in China showed slightly higher complete remission rates of T2DM compared with our study, possibly due to the absence of rigorous FPG criteria. A meta-analysis[1] of RCTs involving 381 Caucasians with T2D who underwent metabolic surgery showed a 27.5% remission rate at 5 years. The inclusion of adjustable gastric banding (AGB) data may be related to the poorer long-term efficacy. Another meta-analysis[4] with 240 non-severely obese subjects (60% Chinese) showed similar T2D remission rates for RYGB and SG (54.0% and 56.7%, respectively), comparable to our findings. Moriconi et al[5] reported that short T2DM duration and good glycemic control before surgery were the best predictors for 10-year remission in Caucasians, consistent with our findings. This study had some limitations. It was a prospective observational study rather than a randomized controlled study. The choice of surgical procedure was not randomized, which prevents direct comparison between RYGB and SG. Additionally, the dropout rate was relatively high (21.8% at 2 years and 37.6% at 5 years), partly due to data collection challenges during the Coronavirus disease (COVID-19) pandemic. These factors could introduce biases and affect the generalizability of the results. The mean duration of diabetes was greater for the cohort that completed the 5-year visit. Mean age, BMI, body weight, waist circumference, systolic blood pressure (SBP), and the proportion of male subjects were somewhat greater for the cohort that did not complete the 5-year visit. In conclusion, this is a prospective, multicenter, 5-year study of metabolic surgery in subjects with T2DM in China. The results of this study provide evidence that metabolic surgery, including RYGB and SG, offers significant long-term benefits for glycemic control and weight loss in Chinese subjects with T2D. These procedures can lead to partial or complete remission of T2D, improving overall metabolic health. Conflicts of interest The authors thank Olivia Mathis of Ethicon, Inc. for editorial assistance. Financial support for this study was provided by Ethicon Endo-Surgery, Inc.

BACKGROUND:Distinguishing bariatric surgical effects on reversing nonalcoholic fatty liver disease (NAFLD) remain unclear. To assess discrepancies in histological response and changes in magnetic resonance imaging-proton density fat fraction (MRI-PDFF) after bariatric surgery. METHODS:This prospective multicenter cohort included 138 NAFLD patients who underwent bariatric surgery and were followed up for 1 year. We obtained paired liver biopsy samples (n = 40), paired proteomic data (n = 23), and sequential MRI-PDFF at 3-, 6-, and 12-month (n = 80, 65, 52, respectively) follow-ups. RESULTS:At 1 year, a ≥2-point improvement in NAFLD activity score (NAS) was observed in 80.0% of patients; nonalcoholic steatohepatitis (NASH) improved without fibrosis worsening in 42.1%; fibrosis improved without NASH worsening in 78.8% (95% confidence interval [CI]: 66.0-91.2, 26.8-58.2, and 63.0-91.3) (all P <0.001). MRI-PDFF discriminated the presence and grading of hepatic steatosis (area under the curve [AUC], 0.94 and 0.95, respectively), indicating liver fat remission (<3.3% or 5.0% at 1 year) in 72.2% or 90.4% of patients (95% CI: 58.4%-83.5% or 78.9%-95.5%; all P <0.001). A ≥78.8% relative decline in MRI-PDFF within 1 year differentiated NAS improvement from non-NAS improvement (AUC, 0.912; 95% CI: 0.79-1.00). Compared to non-NASH remission, NASH remission was associated with significant pre- or postoperative regulation of protein expression levels. CONCLUSIONS:These findings can help evaluate the expected histological response, and aid in understanding the proteomic features resulting from the beneficial surgical effects on NAFLD and its advanced stages in patients with obesity.

Background: Sleeve gastrectomy (SG) is a widely used and effective treatment for patients with obesity and comorbid metabolic abnormalities. No specialized tool is available to predict metabolic syndrome (MS) remission after SG. We aimed to present a nomogram that evaluated the probability of MS remission 1 year after SG. Methods: Patients who underwent SG were enrolled. Of these patients, those with baseline MS were analyzed at the end of follow-up. They were divided into a training set and a validation set. Multivariate logistic regression analysis was performed to identify independent predictors of MS remission 1 year after SG, and these predictors were employed to create a nomogram. Receiver operating characteristic (ROC) curve analysis was used to evaluate discrimination ability. Calibration was performed with the Hosmer-Lemeshow goodness-of-fit test. The net benefits of the nomogram were evaluated using decision curve analysis (DCA). Results: Three hundred and eighteen patients (94 males and 224 females) with a median age of 34.0 years were analyzed at the end of follow-up. They were divided into a training set and a validation set with 159 individuals each. A combination of age, preoperative high-density lipoprotein cholesterol (HDL-c), presence of elevated triglycerides (TG) and the glycated hemoglobin (HbA1c) level independently and accurately predicted MS remission. The nomogram included all four factors. The model showed moderate discrimination in the training and validation sets (Area under curve 0.800 and 0.727, respectively). The Hosmer-Lemeshow X2 values of the nomogram were 8.477 (P=0.388) for the training set and 5.361 (P=0.718) for the validation set, both indicating good calibration. Moreover, DCA showed substantial clinical benefits of the nomogram in both datasets. Conclusions: Our simple nomogram could assist in predicting MS remission in Chinese patients with obesity 1 year after SG. Disclosure Y.Pan: None. X.Han: None. Y.Tu: None. P.Zhang: None. H.Yu: None. Y.Bao: None. Funding Clinical Research Plan of SHDC (2020CR1017B)

Objective: The objective of this study was to determine the role of body fat percentage (BFP) changes in diabetes remission (DR) and the association between baseline body composition and its changes after bariatric surgery. Methods: We analyzed 203 patients with type 2 diabetes who underwent Roux-en-Y gastric bypass. Body composition was measured using a gold-standard-derived predictive equation and magnetic resonance imaging. Body composition changes were calculated as 100 x (baseline value - follow-up value)/baseline value. We verified the results in a laparoscopic sleeve gastrectomy cohort with 311 patients. Results: Compared with non-remission patients in the Roux-en-Y gastric bypass cohort, those who achieved DR showed a higher baseline fat-free mass index (FFMI) and experienced the most significant changes in BFP (p < 0.001). In comparative analyses, BFP changes were significantly better than BMI changes in identifying short- and long-term DR. Linear regression analysis identified FFMI as the most significant baseline variable correlated with BFP changes (p < 0.001). Baseline BMI was positively correlated with changes in BFP but negatively correlated with changes in FFMI. These findings were replicated in the laparoscopic sleeve gastrectomy cohort. Conclusions: BFP changes determine DR after bariatric surgery, and baseline FFMI is crucial for BFP changes. A low initial BMI is associated with a smaller BFP reduction and greater FFMI loss after bariatric surgery.

Background: Performing bariatric surgery on patients with a BMI of over 50 kg/m 2 is challenging. This study aimed to explore the status and challenges related to the perioperative management of such patients in China. Materials and methods: A prospective survey was designed to investigate the perioperative management of patients with a BMI of greater than or equal to 50 kg/m 2 undergoing bariatric surgery in China. The questionnaire of our survey included general information, preoperative management measures, surgical procedures performed, technical details regarding anaesthesia, and postoperative management measures. A response from only one attending physician per bariatric centre was accepted. Results: Physicians from a total of 101 hospitals responded to the questionnaire, and the questionnaire data from 98 hospitals were complete. These centres had completed a total of 44 702 bariatric surgeries since the launch of such surgery to December 2021. A total of 3280 patients had a BMI exceeding 50 kg/m 2 . The preferred surgical procedures for patients with super obesity were sleeve gastrectomy by 62 centres, Roux-en-Y gastric bypass by 11 centres, sleeve gastrectomy plus jejunojejunal bypass by 19 centres, one anastomosis gastric bypass by 1 centre, and duodenal switch by 1 centre. The most worrying issues were cardiopulmonary failure and difficulty in extubation. 91 centres believed that preoperative weight loss was beneficial. A low-calorie diet was the specific measure mainly implemented, only three centres considered using intragastric balloon placement. Postoperative management measures varied greatly. Conclusion: Bariatric surgery has seen rapid development. Chinese physicians show significant differences regarding the perioperative management for patients with a BMI of over 50 kg/m 2 . The perioperative risks of these patients remain relatively high, making further development of clinical pathways is necessary.

Abstract Background: AKT inhibitor was reported to be a potential treatment for drug-resistant tumors by reducing AKT activity, and a synergistic agent of ICIs. Afuresertib is an oral pan-AKT inhibitor that has shown clinical efficacy in multiple tumors. The phase I part of this study assessed the safety, tolerability, and anti-tumor activity of the combination therapy of LAE005 (PD-L1 antibody) plus afuresertib plus nab-paclitaxel in advanced solid tumors, primarily in TNBC. Methods: This is a multi-center, open-label, dose-escalation and proof-of-concept phase I/II study (NCT05390710). In phase I part, patients with advanced solid tumors (TNBC preferred) who have failed 0 to 3 lines of standard treatment are eligible. ECOG score 0-1. Efficacy evaluation is based on RECIST 1.1. Dose escalation uses Bayesian optimal interval (BOIN) design. Results: As of December 11, 2023, 22 subjects were enrolled and dosed. The median prior line of systematic anti-tumor therapy was 1 (0-3), including chemotherapy, PAPR inhibitor or ICIs. Six subjects (3 TNBC, 2 HR+ BC, 1 lung adenocarcinoma) were enrolled in cohort 1 (afuresertib 100 mg PO QD + LAE005 1200 mg IV Q3W + nab-paclitaxel 125 mg/m2 IV D1, D8, Q3W). Six TNBC subjects were enrolled in cohort 2 (afuresertib 100 mg PO QD + LAE005 1200 mg IV Q3W + nab-paclitaxel 100 mg/m2 IV D1, D8, Q3W). 10 TNBC subjects were enrolled in cohort 3 (afuresertib 125 mg PO QD + LAE005 1200 mg IV Q3W + nab-paclitaxel 100 mg/m2 IV D1, D8, Q3W). 2, 0, 2 dose-limiting toxicity (DLT) cases were reported out of 6, 6, 7 DLT evaluable subjects in cohort 1, 2, 3, respectively. DLTs were grade 3 rash (including rash, rash maculopapular, and erythema multiforme) and fever. The most common treatment-emergent AEs were rash (90.9%), white blood cell count decreased (81.8%), and neutrophil count decreased (77.3%). The most common grade 3 or above AEs were neutrophil count decreased (40.9%), white blood cell count decreased (36.4%), rash (18.2%) and lymphocyte count decreased (18.2%). Most of the AEs are manageable, reversible, and recovered after routine treatments. The median follow-up time for 19 TNBC subjects was 16.0 months (min-max: 8.7-28.9 months). The median PFS of these TNBC subjects was 5.4 months (95% CI: 1.4-14.0 months). Among 14 TNBC patients who completed at least 2 cycles of treatment, 5 cases had confirmed PR (ORR 35.7%), 4 cases (28.6%) had SD as the best response. DCR was 64.3%, ORR in three cohorts was 1/2, 2/5, 2/7, respectively. The median DOR was 9.26 months (95%CI: 2.3-NE months).5 TNBC subjects were treated for more than 32 weeks, and the longest duration of treatment was 73 weeks. Conclusions: The triplet regimen shows a manageable safety profile and encouraging preliminary activity in the drug resistant TNBC patients. This triplet regimen warrants further investigation. Citation Format: Binghe Xu, Pin Zhang, Ying Wang, Zhongsheng Tong, Tingjing Yao, Xian Wang, Zijia Wang, Pengfei Guo, Wenyue Ma, Yong YUE. Phase I/II clinical trials of LAE005, afuresertib plus nab-paclitaxel in patients with advanced solid tumors, primarily in patients with triple-negative breast cancer (TNBC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT128.

Background::Management of gastric leak after sleeve gastrectomy (SG) is challenging due to its unpredictable outcomes. We aimed to summarize the characteristics of SG leaks and analyze interventions and corresponding outcomes in a real-world setting.Methods::To retrospectively review of 15,721 SG procedures from 2010 to 2020 based on a national registry. A cumulative sum analysis was used to identify a fitting curve of gastric leak rate. The Kaplan–Meier method and log-rank tests were performed to calculate and compare the probabilities of relevant outcomes. The logistic regression analysis was conducted to determine the predictors of acute leaks.Results::A total of 78 cases of SG leaks were collected with an incidence of 0.5% (78/15,721) from this registry (6 patients who had the primary SG in non-participating centers). After accumulating 260 cases in a bariatric surgery center, the leak rate decreased to a stably low value of under 1.17%. The significant differences presented in sex, waist circumference, and the proportion of hypoproteinemia and type 2 diabetes at baseline between patients with SG leak and the whole registry population ( P = 0.005, = 0.026, <0.001, and = 0.001, respectively). Moreover, 83.1% (59/71) of the leakage was near the esophagogastric junction region. Leakage healed in 64 (88.9%, 64/72) patients. The median healing time of acute and non-acute leaks was 5.93 months and 8.12 months, respectively. Acute leak (38/72, 52.8%) was the predominant type with a cumulative reoperation rate >50%, whereas the cumulative healing probability in the patients who required surgical treatment was significantly lower than those requring non-surgical treatment ( P = 0.013). Precise dissection in the His angle area was independently associated with a lower acute leak rate, whereas preservation ≥2 cm distance from the His angle area was an independent risk factor. Conclusions::Male sex, elevated waist circumference, hypoproteinaemia, and type 2 diabetes are risk factors of gastric leaks after SG. Optimizing surgical techniques, including precise dissection of His angle area and preservation of smaller gastric fundus, should be suggested to prevent acute leaks.

The prevalence of type 2 diabetes (T2D) among adults in China is 10.9%-13.2%. Multicenter, long-term, prospective studies evaluating bariatric/metabolic surgery in obese patients with T2D in China are limited. This prospective study evaluated the 5-year impact of laparoscopic Roux-en-Y gastric bypass (RYGB; n=76 subjects, mean [SD] age 36.4 [9.5], 52.6% women, mean [SD] BMI 34.6 [4.9] kg/m2, mean [SD] glycosylated hemoglobin A1c [HbA1c] 8.3% [1.7%], mean [SD] duration diabetes 3.7 [2.7]) and sleeve gastrectomy (SG; n=25 subjects, mean [SD] age 41.1 [10.8], 44.0% women, mean [SD] BMI 36.4 [6.0] kg/m2, mean [SD] HbA1c 7.5% [1.5%], mean [SD] duration diabetes 2.4 [2.4]) on T2D at six centers in China from August 2014-April 2021. According to the composite measure of glycemic control for metabolic surgeries as suggested by the American Society for Metabolic and Bariatric Surgery, among 62 subjects evaluable at five years (50 RYGB, 12 SG), complete remission occurred in 28.6% (27.5% RYGB, 33.3% SG), partial remission in 27.0% (29.4% RYGB, 16.7% SG), improvement in 30.2% (29.4% RYBG, 33.3% SG), no change in 9.5% (7.8% RYBG, 16.7% SG), and recurrence in 4.8% (5.9% RYGB). Significant 5-year reductions in HbA1c (RYGB -1.7±2.1%, SG -1.8±1.1%), body weight (RYGB -19.8±8.4 kg, SG -21.2±6.0 kg), and BMI (RYGB -7.1±3.1 kg/m2, SG -7.7±2.1 kg/m2) were observed (all p<0.001). Five-year improvements in triglycerides and high-density lipoprotein cholesterol were also observed. Procedure-related serious adverse events occurred in 8 RYGB subjects (7.9%). To our knowledge, this is the first prospective, multicenter, 5-year study of bariatric/metabolic surgery in subjects with T2D in China. These data demonstrate that RYGB and SG achieved clinically meaningful, sustained impacts on T2D remission in many subjects for up to five years. Bariatric/metabolic surgery has enormous potential to provide a safe and effective option for appropriately selected subjects with T2D in China. Disclosure Y.Bao: None. Y.Tu: None. S.Lin: None. H.Zhang: None. W.Yang: None. J.Yang: None. S.Chen: None. Q.Fan: None. Y.Ma: None. C.Ma: None. J.Waggoner: Employee; Ethicon, Inc., Janssen Research & Development, LLC, Stock/Shareholder; Johnson & Johnson. H.Liang: None. A.Tokarski: Employee; Ethicon, Inc. N.Edwards: Consultant; Boston Scientific Corporation, EMD Serono, Inc., Ethicon, Inc., Johnson & Johnson, Becton, Dickinson and Company. T.Yang: None. R.Zhang: None. W.Jia: None. P.Zhang: None. C.Wang: None. T.Jiang: None. N.Zhang: None. J.Zhu: None. H.Yu: None. J.Han: None. Funding Ethicon, Inc.; Johnson & Johnson

BackgroundSleeve gastrectomy (SG) results in bone mineral density (BMD) loss and varying body composition parameters. However, the effects of body compositions on bone health are controversial. In order to accurately demonstrate their relationship and provide new insights into the causes of BMD loss after sleeve gastrectomy, this study is aimed to investigate the role of changes in body composition in BMD loss 12 months after SG.Methods41 Chinese individuals with obesity (25 women and 16 men) who underwent SG were prospectively examined for at least 12 months. Measurements of anthropometrics, body composition, BMD and blood samples were collected.ResultsFor 12 months, the femoral neck (FN) BMD and total hip (TH) BMD decreased significantly compared with baseline in both sexes but not lumbar spine (LS) BMD. Greater TH BMD loss was observed in men than in women. For the first 6 months post-SG, the FN BMD loss was positively associated with the estimated fat free mass index (eFFMI) reduction in women (adjusted β = 0.77, P = 0.004) and positively associated with reduction of subcutaneous fat area (SFA) in men (r = 0.931, P = 0.007). For 12 months post-SG, the FN BMD loss was negatively associated with visceral fat area (VFA) reduction in women (adjusted β = -0.58, P = 0.027) and men (adjusted β = -0.68, P = 0.032). TH BMD loss was positively associated with waist circumference reduction in women (r = 0.448, P = 0.028).ConclusionFN and TH BMD decrease after SG in both women and men. The changes in body compositions are associated with BMD loss at different time points and bone sites. Our data emphasize the limitation of simply taking the total weight loss (% TWL) as an influencing factor of bone mineral density and the necessity of delineating body composition in relevant studies.

1单吻合口胃旁路术 单吻合口 胃旁路术(one anastomosis gastric bypass,OAGB)是在 Roux-en-Y 胃旁路术(Roux-en-Y gastric by-pass,RYGB)基础上简化的术式,通过建立狭长的胃囊及旷置十二指肠与部分空肠达到减重目的.此术式仅建立一个胃空肠吻合口,手术时间与学习曲线短,操作简捷易于掌握.

The prevalence of type 2 diabetes (T2D) among adults in China is 10.9%-13.2%. Multicenter, long-term, prospective studies evaluating bariatric/metabolic surgery in obese patients with T2D in China are limited. This prospective study evaluated the 5-year impact of laparoscopic Roux-en-Y gastric bypass (RYGB; n=76 subjects, mean [SD] age 36.4 [9.5], 52.6% women, mean [SD] BMI 34.6 [4.9] kg/m2, mean [SD] glycosylated hemoglobin A1c [HbA1c] 8.3% [1.7%], mean [SD] duration diabetes 3.7 [2.7]) and sleeve gastrectomy (SG; n=25 subjects, mean [SD] age 41.1 [10.8], 44.0% women, mean [SD] BMI 36.4 [6.0] kg/m2, mean [SD] HbA1c 7.5% [1.5%], mean [SD] duration diabetes 2.4 [2.4]) on T2D at six centers in China from August 2014-April 2021. According to the composite measure of glycemic control for metabolic surgeries as suggested by the American Society for Metabolic and Bariatric Surgery, among 62 subjects evaluable at five years (50 RYGB, 12 SG), complete remission occurred in 28.6% (27.5% RYGB, 33.3% SG), partial remission in 27.0% (29.4% RYGB, 16.7% SG), improvement in 30.2% (29.4% RYBG, 33.3% SG), no change in 9.5% (7.8% RYBG, 16.7% SG), and recurrence in 4.8% (5.9% RYGB). Significant 5-year reductions in HbA1c (RYGB -1.7±2.1%, SG -1.8±1.1%), body weight (RYGB -19.8±8.4 kg, SG -21.2±6.0 kg), and BMI (RYGB -7.1±3.1 kg/m2, SG -7.7±2.1 kg/m2) were observed (all p<0.001). Five-year improvements in triglycerides and high-density lipoprotein cholesterol were also observed. Procedure-related serious adverse events occurred in 8 RYGB subjects (7.9%). To our knowledge, this is the first prospective, multicenter, 5-year study of bariatric/metabolic surgery in subjects with T2D in China. These data demonstrate that RYGB and SG achieved clinically meaningful, sustained impacts on T2D remission in many subjects for up to five years. Bariatric/metabolic surgery has enormous potential to provide a safe and effective option for appropriately selected subjects with T2D in China. Disclosure Y.Bao: None. Y.Tu: None. S.Lin: None. H.Zhang: None. W.Yang: None. J.Yang: None. S.Chen: None. Q.Fan: None. Y.Ma: None. C.Ma: None. J.Waggoner: Employee; Ethicon, Inc., Janssen Research & Development, LLC, Stock/Shareholder; Johnson & Johnson. H.Liang: None. A.Tokarski: Employee; Ethicon, Inc. N.Edwards: Consultant; Boston Scientific Corporation, EMD Serono, Inc., Ethicon, Inc., Johnson & Johnson, Becton, Dickinson and Company. T.Yang: None. R.Zhang: None. W.Jia: None. P.Zhang: None. C.Wang: None. T.Jiang: None. N.Zhang: None. J.Zhu: None. H.Yu: None. J.Han: None. Funding Ethicon, Inc.; Johnson & Johnson

[This corrects the article DOI: 10.2147/DMSO.S405804.].

Introduction Upper abdominal magnetic resonance (MR) imaging is appropriate for body composition analysis.[1] Especially for individuals with obesity, it is of great value to quantify the hepatic proton density fat fraction (PDFF) and the amount of abdominal adipose tissue during clinical evaluation and for research on obesity-related risks. Analytical results may be used to determine the optimal choice of surgical procedure and evaluate treatment outcomes. Multiple artificial intelligence (AI) algorithms and systems have been developed for the automated measurement of body composition. The basis of AI development and application is to have uniform standards for clinical data acquisition and management. The uneven quality of MR images is one of the major obstacles to AI system development and analytical results. A standardized process of MR scanning and clinical data management is urgently needed. Purpose and Target Audience This guideline aims to standardize data acquisition, utilization, and storage for AI systems that target the automatic quantification of body composition. This guide is recommended for surgeons, clinical researchers, and radiologists who focus on body composition analysis and obesity-related topics, for example, type 2 diabetes, metabolic syndrome, and bariatric surgery. Data Acquisition and Evaluation The standardized data acquisition process guarantees high-quality MR images for AI analysis. An image used for AI labeling and clinical diagnosis must follow the basic process mentioned in the following sections. Subject preparation Patients should have an empty stomach before MR scanning. Metal articles should be removed. For overweight subjects with a large waist circumference, wide-bore MR equipment is preferred. According to clinical practice experience, if the patient is >125 kg, doctors or technicians should carefully evaluate the feasibility of upper abdominal MR examination. One challenge is that the bore may not be sufficiently large to accommodate the subject's abdomen. Furthermore, it may be difficult for the patient to hold their breath during MR examination, leading to significant motion artifacts. MR parameter setting A 3.0-T or 1.5-T MR device is preferred for data acquisition. The standard parameters for MR examination for AI analysis are listed in Supplementary Table 1, https://links.lww.com/CM9/A951. PDFF is a reliable measure that can be used to accurately evaluate hepatic steatosis.[2] The Dixon image is 3-dimensional with high resolution. The fat image at the axial level of lumbar 1 to lumbar 2 (L1–L2) intervertebral disc on the Dixon image is considered the best choice for quantifying adipose tissue.[1] If a 1.5-T MR device cannot perform 3-dimensional Dixon imaging, dual-echo scanning is also available. Availability of the MR image for AI quantification All acquired images should be saved in the Digital Imaging and Communications in Medicine (DICOM) format, as the slice thickness and other important information can be stored. The image quality required by the AI analysis is similar to that required for clinical diagnosis. Overall, images with significant artifacts are judged not acceptable. The other requirements for different applications are listed in the following sections. The image quality required for PDFF quantification is usually high.[1] For AI analysis of hepatic PDFF, the first step is to recognize the margin of the liver parenchyma. For patients with hepatic steatosis over grade 2 (PDFF >17.4%),[2] the signal intensity of the liver parenchyma is significantly higher than that of the vessels and adjacent organs. As a result, the margin of the liver is relatively easy for the AI system to recognize. However, for patients with hepatic steatosis grade 1 (6.4% < PDFF ≤ 17.4%),[2] the margin of the liver parenchyma is difficult to recognize. Therefore, AI annotation may not be precise. For subjects without hepatic steatosis (PDFF ≤6.4%),[2] AI annotation may fail if only based on PDFF images. The principles and examples of different degrees of hepatic steatosis are listed in Supplementary Table 2, https://links.lww.com/CM9/A951. According to the recently developed appropriateness criteria, a Dixon sequence image of fat at the axial level of the L1–L2 intervertebral disc can be used for abdominal adipose tissue quantification.[1] It is essential to cover the skin of the abdomen; otherwise, subcutaneous adipose tissue (SAT) cannot be measured. Owing to an insufficient field of view, parallel acquisition, or an uneven magnetic field, the quality of the image may vary. The principles and examples of different image quality degrees are shown in Supplementary Table 3, https://links.lww.com/CM9/A951. Comprehensive evaluation of MR image quality Quality evaluation of both the PDFF and fat images should be considered. These principles are listed in Supplementary Table 4, https://links.lww.com/CM9/A951. Annotation standards Image for PDFF quantification The whole liver parenchyma should be included. Large vessels, local lesions, regions beyond the margin of the liver, and imaging artifacts should be avoided [Figure 1A].Figure 1: Examples of annotation. (A and B) Annotated areas on a PDFF image. The whole parenchyma of the liver is Included. Large vessels, local lesions, regions beyond the margin of the liver, and imaging artifacts are avoided. Different segments of the liver are also annotated. (C and D) Annotated areas on a fat image of the Dixon sequence at the axial level of the L1–L2 intervertebral disc. The red color represents SAT (19,287 mm2), while the green color represents VAT (9718 mm2). L1–L2: Lumbar 1 to lumbar 2; PDFF: Proton density fat fraction; SAT: Subcutaneous adipose tissue; VAT: Visceral adipose tissue.The average PDFF value can be calculated by averaging the values of all voxels included in the region of interest. Since the PDFF value and its change after bariatric surgery vary in different parts of the liver,[3] AI systems are being developed to record the values of different liver segments [Figure 1B]. Image for abdominal adipose tissue quantification Visceral adipose tissue (VAT) and SAT can be recognized and labeled. Different regions of interest, for example, muscle, can also be defined for analysis [Figure 1C and 1D]. The images can be labeled automatically using AI[4] or manually using ITK-SNAP 3.8.0 software (http://www.itksnap.org/). Since a single slice of an MR image is volumetric, the value acquired after labeling is influenced by slice thickness. The volume is calculated as the Supplementary formulas, https://links.lww.com/CM9/A951. Database management For clinical follow-up and research, it is recommended to set up a database to manage clinical data and MR images. Data registry The clinical and radiological data should be registered in a standardized database. For example, there is a prospective national registry database named the “Greater China Metabolic and Bariatric Surgery Database” (GC-MBD®) (Clinicaltrial.gov: NCT03800160) where data of >10,000 cases have been recorded. Data quality control The database needs a committee to hold regular meetings to discuss issues concerning quality control. It is highly recommended that a multidisciplinary team achieve a consensus on the variables in the database. For example, according to the consensus of surgeons, radiologists, clinical researchers, and statisticians, variables that should be documented in the GC-MBD include, but are not limited to, structured demographic information, laboratory tests, PDFF values, VAT and SAT values, biological sample information, and adverse event records. Upper abdominal MR images in the DICOM format should also be uploaded. Before data entry, it is essential for the team's main participants to undergo training. The manager of the database should check and verify the authenticity, accuracy, and integrity of all information according to the source data. Data modification traces should be recorded in the system. After verification, the data should be locked. Discussion There are three key points in AI analysis of body composition using upper abdominal MR images: uniform data acquisition standards, imaging annotation, and database management. This guideline will promote the development and application of AI systems for the automatic quantification of PDFF and abdominal adipose tissue. The PDFF value can significantly influence the availability of PDFF images. For patients without hepatic steatosis, the grayscale contrast between the hepatic parenchyma and vessels is insufficient to train the neural network of the AI system. New strategies may solve this problem. For example, the liver may need to be registered with other higher contrast sequences (eg, axial T1-weighted imaging[5] or portal venous phase of contrast-enhanced imaging[6]) to achieve margin recognition for the AI system. As such, additional MR sequences and related parameter standards are required. Whole-body MR imaging can precisely quantify the volume of adipose tissue. For timesaving, scanning and analyzing a single-slice abdominal MR is preferred. Since imaging annotation for AI analysis requires only a single slice image of fat, we can acquire a single slice at the axial level of the L1–L2 intervertebral disc during the Dixon sequence acquisition to achieve further reduction of scanning time. Clinical practice guideline registration and ethical approval This guideline was registered on the International Practice Guideline Registry (IPGRP-2021CN177). This work was approved by the Ethics Committees of Beijing Friendship Hospital, Capital Medical University (No. 2018-P2-022-01). Funding This work was supported by the National Natural Science Foundation of China (No. 62171297), the Capital's Funds for Health Improvement and Research (No. 2020-1-2021), and the Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support (No. ZYLX202101). Conflicts of interest None.

IntroductionPrevious studies have demonstrated that one anastomosis gastric bypass (OAGB) is not inferior to Roux-en-Y gastric bypass (RYGB) in treating obesity. However, high level evidence comparing the efficacy and safety of both procedures in type 2 diabetes (T2D) treatment is still lacking, which is another main aim of bariatric surgery. The presented trial has been designed to aim at investigating the superiority of OAGB over the reference procedure RYGB in treating T2D as primary endpoint. And diabetes-related microvascular and macrovascular complications, cardiovascular comorbidities, weight loss, postoperative nutritional status, quality of life and overall complications will be followed up for 5 years as secondary endpoints.Methods and analysisThis prospective, multicentre, randomised superiority open-label trial will be conducted in patients of Asian descent. A total of 248 patients (BMI≥27.5 kg/m2) who are diagnosed with T2D will be randomly assigned (1:1) to OAGB or RYGB with blocks of four. The primary endpoint is the complete diabetes remission rate defined as HbA1c≤6.0% and fasting plasma glucose≤5.6 mmol/L without any antidiabetic medications at 1 year after surgery. All secondary endpoints will be measured at different follow-up visit points, which will start at least 3 months after enrolment, with a continuous annual follow-up for five postoperative years in order to provide solid evidence on the efficacy and safety of OAGB in patients with T2D.Ethics and disseminationThe study has been approved by the ethics committee of leading centre (Beijing Friendship Hospital, Capital Medical University, no. 2021-P2-037-03). The results generated from this work will be disseminated to academic audiences and the public via publications in international peer-reviewed journals and conferences. The data presented will be imported into a national data registry. Findings are expected to be available in 2025, which will facilitate clinical decision-making in the field.Trial registration numberNCT05015283.

Saprolegnia diclina DNA has been fractionated using preparative AgNO3/Cs2SO4 and CsCl density gradients. In addition to the previously identified major satellite DNA, there are two minor DNA components banding at 1.682 and 1.701 g · cm−3 in CsCl. Purified major satellite DNA bands at 1.707 g · cm−3 giving a base composition of 48% G + C in good agreement with 47% G + C calculated from its Tm value. The nuclear DNA base composition is 58% G + C by both methods. The base composition of the major satellite DNA suggests that it may represent ribosomal DNA cistrons.

BackgroundSleeve gastrectomy is an effective bariatric procedure; however, sleeve gastrectomy-related adverse skeletal outcomes have been increasingly reported. High levels of sex hormone-binding globulin (SHBG) have been documented to be a risk factor of bone mineral density (BMD) loss with different effects observed between sexes. The aim of this study was to identify sex-specific changes in BMD following sleeve gastrectomy and to evaluate the role of SHBG in this process.MethodsThis retrospective study included 19 middle-aged men and 30 non-menopausal women with obesity who underwent sleeve gastrectomy in China. Anthropometrics, bone turnover markers, calciotropic hormones, BMD, SHBG, and gonadal steroids were measured preoperatively and at 6 and 12 months postoperatively. Longitudinal changes in BMD, bone turnover markers and SHBG were compared between sexes by linear mixed models. Multiple stepwise regression analysis was used to identify the predictors of BMD loss at the investigated bone sites.ResultsOver the 12-month study period, total hip and femoral neck BMD decreased, while lumbar spine BMD remained largely unchanged in both sexes. Linear mixed models revealed significant sex × time interaction effects in total hip BMD and SHBG, showing that men had a significantly greater reduction in total hip BMD and less increase in SHBG after sleeve gastrectomy than women. In the multivariate model, SHBG was significantly associated with total hip BMD loss in men (adjusted β = −0.533, P = 0.019) but not women while total estrogen was significantly associated with total hip BMD loss in women (adjusted β = 0.508, P = 0.01) but not men.ConclusionSignificant sex-specific BMD changes were observed after sleeve gastrectomy in the current study. Sleeve gastrectomy-related increase in SHBG may be a specific risk factor for total hip BMD loss in men. Our results indicate that sex-specific screening may be warranted to facilitate personalized postoperative bone care in this population.

Background: Diabetes remission after bariatric surgery was reported to be characterized by increased risk of hypoglycemia. Objectives: This study aimed to examine the contribution of glycemic variability (GV) to the risk of hypoglycemia, and the suitability of time in range (TIR), an emerging glycemic marker, to define diabetes remission after Roux-en-Y gastric bypass (RYGB). Setting: A single referral center in China. Methods: This retrospective study included 175 individuals with type 2 diabetes and obesity who underwent RYGB. Subjects were classified as remission/nonremission according to the current standard. Each participant underwent continuous glucose monitoring both before and 1 year after RYGB. GV was measured by glucose coefficient of variation (CV), and hypoglycemia was assessed by time below range (TBR). Results: Complete remission was achieved in 88 of the 175 participants following RYGB. In the remission group, significant correlations between postoperative CV and TBRs (r = .353-.442, both P <= .001) were found. Excess hypoglycemia (TBR<54, >= 1%, TBR<70, >= 4%) increased with ascending CV quintiles (both P for trend <.05) and was significantly more frequent in subjects with glucose CV >32.2% (both P <.05). Compared with glycated hemoglobin A1C, TIR showed stronger correlation with glucose CV and risk of hypoglycemia. Conclusion: Increased glycemic variability was linked to excess risk of hypoglycemia after RYGB. Furthermore, TIR may serve as a new metric, in addition to HbA1C, for defining diabetes remission. (C) 2022 Published by Elsevier Inc. on behalf of American Society for Bariatric Surgery.

Background The effect of different administration routes of omeprazole remains unclear on the recovery in patients with obesity after laparoscopic sleeve gastrectomy (LSG). Methods We designed a randomized clinical trial enrolling 120 patients with a BMI≥32.5 kg/m2 after LSG. They were randomized into two groups to be administered with omeprazole by rapid intravenous injection (group A) or by continuous micropump infusion (group B). The plasma concentration of omeprazole was monitored upon initiating administration. Change in intragastric pH and gastrointestinal symptoms during follow-up served as indicators for therapeutic evaluation. Results Patients in the two groups showed no difference in the AUC curves (P=0.25), but group A had significantly higher peak concentration (P<0.001), and shorter time to reach peak concentration after administration (P<0.001), compared to group B. Before and after the administration of omeprazole, the average change in intragastric pH was much lower in group A (0.031 ± 0.61) than in group B (0.48 ± 0.74) (P=0.004). The incidence of gastrointestinal symptoms was similar between the two groups (P=0.85); however, the average duration of remaining symptoms was longer in group A (3.97 months; 95% CI, 2.90–5.04) than in group B (2.82 months; 95% CI, 2.01–3.63) (P=0.04). Conclusion Continuous micropump infusion of omeprazole may improve the outcomes in patients with obesity after LSG. Trial registration China Clinical Trial Registration Center (ChiCTR), ChiCTR-IPR-17013365. Registered 13 November 2017. http://www.chictr.org.cn/showproj.aspx?proj=22892.

背 景 肥胖代谢外科手术是目前治疗肥胖症及相关代谢病最有效的方式之一,手术量逐年稳步增长[1].中国肥胖代谢外科数据库2019年度报告统计估算2019年中国年手术量超过10000例[2],相关手术方式也越来越多.然而其中不少手术方式并不规范或尚缺乏中长期疗效数据及充分的循证医学证据,开展时需慎重考量[3,4].为此,中国医师协会外科医师分会肥胖和糖尿病外科医师委员会(Chinese Society for Metabolic & Bariatric Surgery,CSMBS)与中国肥胖代谢外科研究协作组(COMES Collaborative)组织我国肥胖代谢外科专家,先后经问卷调查、会议讨论后制定本立场声明,以规范我国肥胖代谢外科手术方式选择,旨在为开展肥胖代谢外科手术的医生在临床决策、术式选择上提供参考和依据,促进行业规范健康地发展.