Circulating B Cell-Derived Small RNA Delivered by Extracellular Vesicles: A Dialogue Mechanism for Long-Range Targeted Renal Mitochondrial Injury in Obesity.

The intricate processes that govern the interactions between peripatetic immune cells and distal renal injury in obesity are not fully understood. Employing transcriptomic analysis of circulating extracellular vesicles (EVs), a marked amplification of small RNA (miR-3960) is discerned within CD3-CD19+ B cells. This RNA is found to be preferentially augmented in kidney tissues, contrasting with its subdued expression in other organs. By synthesizing dual-luciferase reporter assay with co-immunoprecipitation analysis, it is pinpointed that miR-3960 specifically targets the nuclear gene TRMT5, a pivotal actor in the methylation of mitochondrial tRNA. This liaison instigates aberrations in the post-transcriptional modifications of mitochondrial tRNA, engendering deficiencies within the electron respiratory chain, primarily attributable to the diminution of the mitochondrial bioenergetic compound (NDUFA7) complex I. Such perturbations lead to a compromised mitochondrial respiratory capacity in renal tubular cells, thereby exacerbating tubular injury. In contrast, EV blockade or miR-3960 depletion markedly alleviates renal tubular injury in obesity. This investigation unveils a hitherto unexplored pathway by which obesity-induced circulating immune cells remotely manipulate mitochondrial metabolism in target organs. The strategic targeting of obese EVs or infiltrative immune cells and their specifically secreted RNAs emerges as a promising therapeutic avenue to forestall obesity-related renal afflictions.

30-day morbidity and mortality of revisional bariatric surgery - An international multi-centre collaborative (BROAD) study.

INTRODUCTION: Revisional bariatric surgery (RBS) for insufficient weight loss/weight regain or metabolic relapse is increasing worldwide. There is currently no large multinational, prospective data on 30-day morbidity and mortality of RBS. In this study, we aimed to evaluate the 30-day morbidity and mortality of RBS at participating centres. METHODS: An international steering group was formed to oversee the study. The steering group members invited bariatric surgeons worldwide to participate in this study. Ethical approval was obtained at the lead centre. Data were collected prospectively on all consecutive RBS patients operated between 15th May 2021 to 31st December 2021. Revisions for complications were excluded. RESULTS: A total of 65 global centres submitted data on 750 patients. Sleeve gastrectomy (n = 369, 49.2 %) was the most common primary surgery for which revision was performed. Revisional procedures performed included Roux-en-Y gastric bypass (RYGB) in 41.1 % (n = 308) patients, One anastomosis gastric bypass (OAGB) in 19.3 % (n = 145), Sleeve Gastrectomy (SG) in 16.7 % (n = 125) and other procedures in 22.9 % (n = 172) patients. Indications for revision included weight regain in 615(81.8 %) patients, inadequate weight loss in 127(16.9 %), inadequate diabetes control in 47(6.3 %) and diabetes relapse in 27(3.6 %). 30-day complications were seen in 80(10.7 %) patients. Forty-nine (6.5 %) complications were Clavien Dindo grade 3 or higher. Two patients (0.3 %) died within 30 days of RBS. CONCLUSION: RBS for insufficient weight loss/weight regain or metabolic relapse is associated with 10.7 % morbidity and 0.3 % mortality. Sleeve gastrectomy is the most common primary procedure to undergo revisional bariatric surgery, while Roux-en-Y gastric bypass is the most commonly performed revision.

Recompensation in MASLD-related cirrhosis via metabolic bariatric surgery.

The prognosis of patients with decompensated cirrhosis is poor, with significantly increased liver-related mortality rates. With the rising tide of decompensated cirrhosis associated with metabolic dysfunction-associated steatotic liver disease (MASLD), the role of metabolic bariatric surgery (MBS) in achieving hepatic recompensation is garnering increasing attention. However, the complexity of preoperative assessment, the risk of postoperative disease recurrence, and the potential for patients to experience surgical complications of the MBS present challenges. In this opinion article we analyze the potential of MBS to induce recompensation in MASLD-related cirrhosis, discuss the mechanisms by which MBS may affect recompensation, and compare the characteristics of different MBS procedures; we highlight the therapeutic potential of MBS in MASLD-related cirrhosis recompensation and advocate for research in this complex area.

Comprehensive pharmacological and experimental study of Ginsenoside Re as a potential therapeutic agent for non-alcoholic fatty liver disease.

OBJECTIVE: Ginsenoside Re, a unique tetracyclic triterpenoid compound found in ginseng, has been suggested in previous reports to improve non-alcoholic fatty liver disease (NAFLD) by modulating lipid imbalance. This study aims to elucidate the potential mechanisms of Ginsenoside Re in treating NAFLD through a combination of bioinformatics analysis and biological experiments. METHODS: Network pharmacology methods were employed to systematically depict the effective components and mechanisms of Ginsenoside Re in improving NAFLD. Molecular docking was utilized to evaluate the binding affinity of Ginsenoside Re with NAFLD-related targets and identify potential targets. NAFLD-related target genes were obtained from the GEO database for gene enrichment analysis, revealing signaling pathways, biological processes, and gene differential expression. Finally, animal experiments were conducted to verify the mechanism of action of Ginsenoside Re in NAFLD. RESULTS: Network pharmacology analysis revealed that Ginsenoside Re improves NAFLD by modulating targets such as AKT1 and TLR4, findings corroborated by molecular docking, GEO database analysis, and experimental validation. Further investigation found that Ginsenoside Re ameliorates lipid metabolism disorders and inflammatory responses induced by NAFLD by modulating the PI3K/AKT and TLR4/NF-κB signaling pathways. CONCLUSION: Our study demonstrates the pharmacological effects of Ginsenoside Re in treating NAFLD, implicating multiple components, targets, and pathways. This provides a solid foundation for considering Ginsenoside Re as an alternative therapy for NAFLD, with promising clinical applications.

A global survey on the use of the international classification of diseases codes for metabolic dysfunction-associated fatty liver disease.

BACKGROUND: With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11. METHODS: Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members. RESULTS: A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p = 0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%). CONCLUSIONS: This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision.

Remnant Gastrectomy and Gastric Bypass: A Systematic Review of Indications and Outcomes of Resectional Gastric Bypass.

BACKGROUND: In this systematic review, we aim to evaluate the reasons and outcomes behind remnant gastrectomy with or after gastric bypass procedures. RESULTS: A total of 66 studies examining 1918 patients were included in this study with 70% of female predominance. Twenty studies reported RGB on 1751 patients and 46 studies reported remnant gastrectomy after gastric bypass in 167 patients. The most common etiology of RGB was related to the in situ remnant stomach neoplasia in 10 studies on 981 patients; mostly for preventive intentions in high prevalence areas. Remnant gastrectomy after gastric bypass was performed to treat a complication such as GGF, retrograde bile reflux gastritis, cancer mostly adenocarcinoma. Studies revealed that RGB has similar weight loss in comparison to standard Roux-en-Y gastric bypass.

Metabolic Dysfunction-Associated Steatohepatitis Detected by Neutrophilic Crown-Like Structures in Morbidly Obese Patients: A Multicenter and Clinicopathological Study.

Metabolic dysfunction-associated steatohepatitis (MASH) is the progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD), and closely associated with a high risk of liver-related morbidity and mortality. Although enhanced neutrophil infiltration of the liver is a histological hallmark of MASH, the morphological pattern of hepatic neutrophils and their relevance to the definition of MASH remain unknown. This clinicopathological study aimed to determine the association of neutrophilic crown-like structures (CLSs) in liver biopsies and evaluate their relevance to the histological diagnosis of MASH. A total of 483 morbidly obese adults who underwent bariatric surgery were recruited. Neutrophilic CLSs in liver biopsies were detected by immunohistochemistry for neutrophil elastase and proteinase 3. All participants were classified into 4 histological subgroups: no MASLD (118, 24.4%), MASLD (76, 15.7%), borderline MASH (185, 38.3%), and definite MASH (104, 21.5%). In the discovery cohort (n = 379), the frequency of neutrophilic CLSs increased in line with the severity of liver disease. The number of neutrophilic CLSs was positively correlated with established histological characteristics of MASH. At a cutoff value of <0.3 per 20× microscopic field, the number of neutrophilic CLSs yielded a robust diagnostic accuracy to discriminate no MASLD and MASLD from borderline MASH and definite MASH; a cutoff at >1.3 per 20× microscopic field exhibited a statistically significant accuracy to distinguish definite MASH from other groups (no MASLD, MASLD, and borderline MASH). The significance of neutrophilic CLSs in identifying borderline MASH and definite MASH was confirmed in an external validation cohort (n = 104). The frequency of neutrophilic CLSs was significantly higher than that of macrophagic CLSs. In conclusion, neutrophilic CLSs in the liver represent a typical histological characteristic of MASH and may serve as a promising indicator to improve the diagnostic accuracy of MASH during histological assessment of liver biopsies.

ChatGPT/GPT-4 (large language models): Opportunities and challenges of perspective in bariatric healthcare professionals.

ChatGPT/GPT-4 is a conversational large language model (LLM) based on artificial intelligence (AI). The potential application of LLM as a virtual assistant for bariatric healthcare professionals in education and practice may be promising if relevant and valid issues are actively examined and addressed. In general medical terms, it is possible that AI models like ChatGPT/GPT-4 will be deeply integrated into medical scenarios, improving medical efficiency and quality, and allowing doctors more time to communicate with patients and implement personalized health management. Chatbots based on AI have great potential in bariatric healthcare and may play an important role in predicting and intervening in weight loss and obesity-related complications. However, given its potential limitations, we should carefully consider the medical, legal, ethical, data security, privacy, and liability issues arising from medical errors caused by ChatGPT/GPT-4. This concern also extends to ChatGPT/GPT -4's ability to justify wrong decisions, and there is an urgent need for appropriate guidelines and regulations to ensure the safe and responsible use of ChatGPT/GPT-4.

Effects of bariatric surgery on sexual function and fertility: A narrative review.

Obesity has emerged as a prevalent global health concern, with its detrimental effects on the reproductive system and sexual function garnering increasing attention. Both men and women affected by obesity face a heightened risk of fertility challenges and sexual dysfunction. Although fertility and sexual function are distinct topics, they are intricately linked and mutually influential in both medical and societal contexts. Bariatric surgery (BS) has generated promising results in alleviating sexual dysfunction and enhancing fertility, results which are often gender specific. In men, improvements in sexual function can often be attributed to weight loss and subsequent optimizations in sex hormone levels. However, improving female sexual function may be related to a range of factors beyond weight loss. Bariatric procedures have shown limited benefits for male fertility; in fact, in some situations it can even be detrimental, leading to a decrease in sperm count and quality. Conversely, BS may positively impact female fertility, improving pregnancy and neonatal outcomes. Nevertheless, it is essential to consider the potential risks related to the adverse effects of malnutrition and rapid weight loss following BS, making it advisable to wait for 12-18 months before attempting pregnancy.

Auricular Acupressure in Relieving PONV and Promoting Gastrointestinal Function Recovery in Females After Laparoscopic Sleeve Gastrectomy: A Prospective Randomized Controlled Trial.

BACKGROUND: The role of current pharmacological treatment after laparoscopic sleeve gastrectomy (LSG) is limited. The incidence of postoperative nausea and vomiting (PONV) after LSG remains high. Auricular acupressure (AA) is believed to relieve PONV after laparoscopic surgeries, but its role in patients with obesity after LSG has yet to be confirmed. METHODS: Ninety-five female patients who underwent LSG were randomized into two groups: AA combined with conventional anti-nausea medication (AA group, 47 patients) or conventional anti-nausea medication group (control group, 48 patients). Index of nausea and vomiting and retching (INVR) scores, postoperative anti-vomiting medication use, time of first anus exhausting, time of first fluid intake, and time of first to get out of bed were collected within 48 h after surgery. RESULTS: Demographic data of patients in both groups were balanced and comparable. INVR score (F = 7.505, P = 0.007), vomiting score (F = 11.903, P = 0.001), and retching score (F = 12.098, P = 0.001) were significantly lower in the AA group than that in the control group within 48 h postoperatively. Use of metoclopramide was significantly less in the AA group than in the control group (4.7 [5.5]) vs. 8.8 [7.6], P = 0.004); time to first anus exhausting was significantly less in the AA group than in the control group (17.50 [6.00] vs. 20.42 [8.62], P = 0.020). CONCLUSIONS: AA combined with conventional anti-vomiting agents can alleviate PONV in female patients after LSG, and AA can promote gastrointestinal exhaustion. TRIAL REGISTRATION: The trial has been registered in the Chinese Clinical Trial Registry (ChiCTR) with the registration no. ChiCTR2100047381 on June 13, 2021.

Technical Variations and Considerations around OAGB in IFSO-APC and IFSO-MENAC Chapters, an Expert Survey.

OBJECTIVE: This study aimed to evaluate the technical variations of one-anastomosis gastric bypass (OAGB) among IFSO-APC and MENAC experts. BACKGROUND: The multitude of technical variations and patient selection challenges among metabolic and bariatric surgeons worldwide necessitates a heightened awareness of these issues. Understanding different perspectives and viewpoints can empower surgeons performing OAGB to adapt their techniques, leading to improved outcomes and reduced complications. METHODS: The scientific team of IFSO-APC, consisting of skilled bariatric and metabolic surgeons specializing in OAGB, conducted a confidential online survey. The survey aimed to assess technical variations and considerations related to OAGB within the IFSO-APC and IFSO-MENAC chapters. A total of 85 OAGB experts participated in the survey, providing their responses through a 35-question online format. The survey took place from January 1, 2024, to February 15, 2024. RESULTS: Most experts do not perform OAGB for children and adolescents younger than 18 years. Most experts create the gastric pouch over a 36-40-F bougie and prefer to create a gastrojejunostomy, at the posterior wall of the gastric pouch. An anti-reflux suture during OAGB is performed in all patients by 51.8% of experts. Most experts set a common limb length of > 4 m in revisional and conversional OAGBs to prevent nutritional complications. CONCLUSION: The ongoing debate among metabolic and bariatric surgeons regarding the technical variations and patient selection in OAGB remains a significant point of discussion. This survey demonstrated the variations in technical aspects and patient selection for OAGB among MBS surgeons in the IFSO-APC and IFSO-MENAC chapters. Standardizing the OAGB technique is crucial to ensure optimal safety and efficacy in this procedure.

Novice Chinese Bariatric Nurses' Perceptions of Their Role as Bariatric Case Managers: A Qualitative Study.

INTRODUCTION: Bariatric case managers (BCM) are integral healthcare team members for patients undergoing bariatric surgery in China. As the demand for bariatric surgery increases in China, the number of BCMs has also risen. However, more is needed to know about the perceptions of novice bariatric nurses toward their role as case managers. This study aims to investigate the perceptions of novice Chinese bariatric nurses toward their roles during the early stages of their careers. METHODS: This qualitative study employed semi-structured individual interviews with 15 novice bariatric nurses who received training as BCMs. The interviews were audio-recorded, transcribed line-by-line, and analyzed thematically. The study was conducted in a bariatric surgery center of a public tertiary hospital in Southern China. RESULTS: Three themes emerged from the data related to the perceptions of being a BCM: "negotiating the ambiguity of the BCM role," "establishing a core set of behaviors for the BCM role," and "identifying areas of competence to develop a BCM role framework." The novice bariatric nurses expressed both positive and negative feelings toward their role. They highlighted the need for further training to improve their qualifications and the importance of support from colleagues, and hospital management. CONCLUSIONS: The findings illuminate the role of the BCM in China. Future research should investigate effective and acceptable job descriptions and cooperation modes between BCMs, colleagues and hospital management. We recommend using these findings to develop training programs for novice BCMs and improve their capacity to provide quality care to patients undergoing bariatric surgery.

Safety and Efficacy of LSG Versus LRYGB on Patients with Obesity: a Systematic Review and Meta-analysis from RCTs.

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic sleeve gastrectomy (LSG) are the two most frequently performed techniques in treating obesity and its related comorbidities. We aimed to compare the clinical efficacy and safety of LSG with LRYGB in terms of short- and mid-term outcomes of weight loss, obesity-related comorbidities, and post-operative complications via a meta-analysis of RCTs. METHODS: Clinical comparative RCTs on LSG and LRYGB were searched through PubMed, MEDLINE, and Web of Science databases from inception to August 2022. Pooled outcomes from the selected studies were discussed by the random-effect meta-analysis method. Quality assessment and risk of bias for selected RCTs were implemented, and all the statistical analyses were performed. RESULTS: Twenty studies, including 1270 patients, were enrolled. Meta-analysis results indicated the great superior efficacy of LRYGB to LSG in BMI loss at 6 (MD -1.35 kg/m2, 95% CI: -2.07 to -0.62, p = 0.0003), 12 months (MD -1.09 kg/m2, 95% CI: -1.86 to -0.33, p = 0.005), and 36 months (MD -1.47 kg/m2, 95% CI: -2.77 to -0.16, p = 0.03) as well as %EWL gaining at 36 months. Significantly higher remission rates of T2DM and dyslipidemia were achieved by LRYGB at 12 months. Besides, better improvements for T2DM-related and lipid biochemical parameters were found favoring LRYGB. However, LSG resulted in a lower post-operative complication rate and shorter operating time. CONCLUSIONS: Present meta-analysis results suggested that LRYGB was superior to LSG concerning short- and mid-term weight loss, short-term T2DM remission efficacy, and related biochemical parameters. LSG is favored for obviously fewer complications and shorter operating time.

Correlation of T2DM and Anthropometric Measures with Total Small Bowel Length and Its Effects on Diabetes Remission After Bariatric Surgery.

BACKGROUND: The outcome of weight loss surgery is related to several factors, and for super-obese patients, the rate of weight loss failure and weight recovery after Roux-en-Y gastric bypass (RYGB) is high. Relevant studies have shown that the weight loss effect also correlates with total small bowel length (TSBL) and biliopancreatic (BP) and Roux limbs. However, there are few studies on the relationship between TSBL and anthropometric parameters, the BP limb, the Roux limb, and weight loss effect, and no relevant reports have been reported in China. OBJECTIVES: The objective was to study the relationship between the total length of the small intestine and anthropometric parameters in the Chinese population. The effect of the Roux limb/biliopancreatic limb (RL/BPL) ratio on weight loss and diabetes remission in RYGB patients 1 year after surgery was evaluated to find the appropriate ratio relationship. METHODS: In this prospective study, 148 patients between the ages of 19 and 68 years who underwent laparoscopic Roux-en-Y gastric bypass were enrolled. Height, weight, BMI, the BP limb, the Roux limb, fasting blood glucose (FBG), etc., were noted. To explore the correlation between the total length of the small intestine and these values. Subsequently, the 148 patients were followed up for 1 year after surgery. The patients diagnosed with T2DM before surgery were screened out, and 56 patients were finally identified according to the postoperative follow-up, in which BPL = 50 cm and RL = 150 cm, 175 cm, and 200 cm, respectively. RL/BPL was divided into 3, 3.5, and 4 groups according to the proportional relationship to explore the relationship between RL/BPL and diabetes remission and weight loss. RESULTS: (1) The study included 148 patients (61 women and 87 men). The mean age was 35.68 ± 10.46 years, weight = 127.46 ± 34.51 kg, height = 167.83 ± 9.16 cm, BMI = 44.94 ± 10.58 kg/m2. The average TSBL value was 714.41 ± 101.08 cm. Linear regression analysis showed that TSBL was positively correlated with height, weight, neck circumference, chest circumference, waist circumference, and Roux limb. (2) Fifty-six patients with T2DM who were followed up 1 year after surgery were divided into three groups. Group 1: BPL = 50 cm, RL = 150 cm (n = 20); group 2: BPL = 50 cm, RL = 175 cm (n = 26); group 3: BPL = 50 cm, RL = 200 cm (n = 10); RL/BPL = 3 was associated with higher weight loss than the other groups. The remission rate of diabetes did not differ between the three groups. CONCLUSIONS: TSBL was positively correlated with height, weight, neck circumference, chest circumference, waist circumference, and Roux limb. The TSBL of males was significantly higher than that of females. Among patients with T2DM who participated in the follow-up 1 year after surgery, RL/BPL = 3 (n = 20) had greater weight loss than the other groups.

Identification and multicentric validation of soluble CDCP1 as a robust serological biomarker for risk stratification of NASH in obese Chinese.

The definitive diagnosis of non-alcoholic steatohepatitis (NASH) currently relies on invasive and labor-intensive liver biopsy. Here, we identified soluble CUB domain-containing protein 1 (sCDCP1) as a top-ranked non-invasive biomarker for NASH using Olink-based proteomics in 238 obese individuals with liver biopsies. Both the circulating concentration and hepatic mRNA abundance of sCDCP1 were significantly elevated in patients with NASH and correlated closely with each histological feature of NASH. In the pooled multicenter validation cohort, sCDCP1 as a standalone biomarker achieved an area under the receiver operating characteristic (AUROC) of 0.838 (95% confidence interval [CI] 0.789-0.887) for diagnosing NASH, which is better than those achieved with cytokeratin-18 and other non-invasive tests. Furthermore, the C-DAG model established by the combination of sCDCP1 with diabetes, aspartate aminotransferase (AST), and gender accurately rules in and rules out both NASH and fibrotic NASH (gray zones <20%). Thus, sCDCP1-based non-invasive tests can be potentially implemented for screening and early diagnosis of NASH and for ruling out low-risk individuals to avoid unnecessary liver biopsies.