Hekai Shi

Objective To evaluate perioperative safety, long-term outcomes, and factors associated with Clavien-Dindo grade ≥ II complications in nonagenarians undergoing elective inguinal hernia repair. Methods The main cohort of this retrospective study included nonagenarians who underwent elective inguinal hernia repair between 2013 and2025. Preoperative, intraoperative, and postoperative data were collected. The primary outcome was Clavien-Dindo grade ≥ II complications. Univariable logistic regression was used to identify associated factors. Nonagenarians who underwent emergency groin hernia repair during the same period were analyzed separately as a supplementary descriptive cohort. Results The elective cohort comprised 152 patients (median age 91.0 years), all of whom underwent mesh repair (Lichtenstein in 129, 84.9%). Median hospital stay was 7.0 days, and median follow‑up was 30.0 months. Postoperative complications occurred in 22 patients (14.5%), including 12 (7.9%) with Clavien‑Dindo grade ≥ II. The 30‑day mortality was 1.3%. During the follow‑up, recurrence was detected in 2 patients (1.3%) and chronic pain in 6 (3.9%). In univariate logistic regression, preoperative functional dependence was significantly associated with grade ≥ II complications (odds ratio 16.27, 95% CI 2.82 to 93.86, P = 0.002). In the emergency repair cohort (n = 29), 10 patients (34.5%) developed grade ≥ II complications, all of which were surgery‑related deaths. Conclusions In clinically selected nonagenarians undergoing elective inguinal hernia repair, mesh repair showed acceptable perioperative safety and favorable long-term local outcomes. Preoperative functional status, rather than chronological age alone, should be emphasized in surgical decision-making.

Objective: Different subtypes of hernia exhibit significant familial aggregation. However, the genetic correlations among different hernia subtypes, as well as their shared and subtype-specific candidate genes still remain unclear. Methods: Using genome-wide association study (GWAS) data from the FinnGen consortium, we quantified genetic correlations ( r _g ) among diaphragmatic (16 034 cases), inguinal (43 066 cases), femoral (1 660 cases), and hernia of abdominal wall (21 210 cases, including umbilical and ventral hernias) by linkage disequilibrium score regression. Mendelian randomization (MR) analyses were performed using 15 695 expression quantitative trait loci (eQTL) as exposures and hernia GWAS data as outcomes. Multiple testing was controlled using the false discovery rate ( q < 0.05), and findings were further prioritized through Bayesian colocalization. Shared candidate genes were validated using fibroblast eQTL data from GTEx V10 and protein quantitative trait loci data from the UK Biobank. Results: Significant genetic correlations were observed across all hernia subtypes ( P < 0.01), with the strongest correlation between ventral and umbilical hernias ( r _g = 0.78), while diaphragmatic hernia exhibited weaker correlations with other subtypes ( r _g = 0.26–0.48). MR analyses using blood and fibroblast-derived eQTL data identified BMP6, MYCBPAP , and ZNF75A as candidate genes shared across multiple hernia subtypes. Proteomic validation further revealed that elevated BMP6 protein levels were associated with a reduced risk for all hernia subtypes. Conclusion: This study reveals a shared genetic basis among common hernia subtypes and identifies three shared candidate genes ( BMP6, MYCBPAP , and ZNF75A ). Elevated BMP6 protein levels were associated with a reduced risk of multiple hernia types. These findings provide new insights into the genetic correlations and potential pathogenic mechanisms underlying hernia. Future functional studies are needed to elucidate the roles of these genes in abdominal wall tissue.

Previous studies have revealed the association between gut microbiota (GM) and temporomandibular joint inflammation, which leads to temporomandibular joint disorders (TMD). However, the causality of the associations remains unknown. This Mendelian randomization (MR) study aims to clarify the causal relationships between GM and TMD. We employed a two-sample MR approach to analyze GM data from the MiBioGen consortium, including 18,340 participants and 211 taxa, and TMD data from the FinnGen consortium R10 release, including 6314 cases and 222,498 controls. Various MR methods, including inverse-variance weighted (IVW), MR-Egger, and weighted median analyses, alongside comprehensive sensitivity analyses, were used to assess causality. After comprehensive sensitivity analyses, the study found causal links between 6 certain GM at the genus level and TMD, including Eubacterium fissicatena group (IVW’s odds ratio [OR] = 1.18; 95% confidence interval [CI]: 1.02–1.37; P = .027), Catenibacterium (IVW’s OR = 1.33; 95% CI: 1.11–1.59; P = .002), Oxalobacter (IVW’s OR = 0.85; 95% CI: 0.75–0.97; P = .013), Ruminococcaceae NK4A214 (IVW’s OR = 0.80; 95% CI: 0.66–0.99; P = .036), and Senegalimassilia (IVW’s OR = 0.75; 95% CI: 0.59–0.96; P = .024). Following replication verification analysis, Catenibacterium (FDR = .04) at the genus level were positively correlated to the risk of TMD. The reverse MR analysis revealed that TMD had no significant effect on the 6 GMs. The findings of this MR study support a strong and negative causal association between genus Catenibacterium and TMD, highlighting potential targets for the prevention and treatment of TMD.

Background: Obesity and type 2 diabetes (T2D) are major public health concerns. Tirzepatide has shown promise in recent clinical trials. This systematic review and meta-analysis aim to evaluate the efficacy and safety of tirzepatide in adults with obesity or type 2 diabetes, compared to placebo, GLP-1 receptor agonists (GLP-1 RAs), and insulin. Method: PubMed, Embase, and the Cochrane Library were searched on 17 January 2024, focusing on phase II and III randomized controlled trials (RCTs). We included studies involving adults with T2D or obesity, comparing tirzepatide to placebo, GLP-1 RAs, or insulin. The primary outcomes were the proportion of participants achieving ≥5%, ≥10%, and ≥15% weight loss targets. Secondary outcomes included changes in body weight, waist circumference, HbA1c levels, and blood pressure. Safety outcomes focused on adverse event rates. Meta-analyses were performed, and risk of bias was assessed using the Cochrane Risk-of-Bias tool version 2. Results: Fourteen RCTs involving 14,713 patients were included. Tirzepatide significantly increased the proportion of participants achieving weight loss targets, and reduced body weight, waist circumference, HbA1c, and blood pressure versus placebo and insulin. Compared with GLP-1 RAs, tirzepatide provided comparable or better outcomes in weight loss, waist circumference, and glycemic control. The incidence of gastrointestinal adverse events was significantly higher at all doses of tirzepatide compared to placebo and insulin. When compared with GLP-1 RAs, higher doses of tirzepatide were associated with increased risk of nausea, diarrhea, and decreased appetite, but not vomiting. Conclusions: Tirzepatide is an effective option for managing weight and improving metabolic outcomes in patients with T2D or obesity. However, it is associated with an increased risk of gastrointestinal adverse events, especially at higher doses. Therefore, close monitoring should be considered in clinical practice. Registration: PROSPERO CRD42021283449.

Purpose Obesity is closely associated with a lower risk of inguinal hernia, but the association between different obesity metrics and the risk of inguinal hernia is still unclear. Methods In our study, we categorized obesity measurement indicators into three groups based on the difficulty of measurement: (1) indicators easily available, such as body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR); (2) indicators accessible with moderate difficulty, such as body fat percentage and body fat mass; (3) indicators difficultly accessible, such as the volume of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Mendelian randomization (MR) analysis was used to investigate the causal relationship between various adiposity measures and the risk of inguinal hernia in both European ancestry and East Asians. Results We identified a total of 17,096 patients with inguinal hernia in the FinnGen cohort and 1664 cases in the Japan Biobank cohort. For European ancestry, MR analysis reported a significant causal association between one standard deviation increase of BMI, WC, HC, body fat percentage, and body fat mass and the lower risk of inguinal hernia, rather than WHR, VAT, and SAT. After the adjustment of BMI, increased WC is still causally associated with a lower risk of inguinal hernia (OR: 0.52; 95% CI: 0.33-0.80; P < 0.01). Among East Asians, only body fat mass is causally associated with a reduced risk of inguinal hernia, rather than BMI, WC, and HC. Conclusion Obesity is causally associated with a relatively lower risk of inguinal hernia. The association between different obesity measures and the risk of inguinal hernia has ethnic specificity. These findings help us deepen our understanding of the intrinsic causal relationship between fat distribution and the risk of inguinal hernias at the genetic level.

Purpose The systemic and local inflammatory response in patients after surgical operation is closely related to the quality of the wound healing. Low-quality wound healing and defects in the suture technique lead to the occurrence of incisional hernia (IH). However, the causal relationship between human circulating inflammatory cytokines, immune cell traits, and the risk of IH remains unclear. Methods We used summary data from genome-wide association studies to assess the causal relationship between 91 types of circulating inflammatory factors, 731 types of circulating immune cell traits, and the risk of IH. The outcome dataset was obtained from FinnGen, including 6,336 patients with IH and 232,612 controls. We performed Mendelian Randomization (MR) analysis to identify their causal relationship and immune cell phenotypes upstream of inflammatory factors. Inverse variance weighting is considered to be the main analysis method. Results Among the identified cytokines, TNF-related activation-induced cytokine levels were associated with a lower risk of IH (OR: 0.89; 95% CI: 0.82–0.96; P = 0.003). In contrast, interleukin-5 levels were associated with an increased risk of IH (OR: 1.18; 95% CI: 1.06–1.31; P = 0.003). Additionally, a significant causal relationship was found between four immune cell traits and the risk of IH (P < 0.01). Through two-step MR analysis, we determined that interleukin-5 levels mediate the causal relationship between the relative count of CD25hi % CD4 + in Treg cells and the higher risk of IH. Conclusion This study found a causal relationship between specific inflammatory cytokines, immune cell traits, and risk of IH. These results can help surgeons predict the risk of IH and take preventive measures.

Parastomal hernias (PSH) are difficult to manage and associated with high rates of postoperative recurrence and complications. Sugarbaker and three-dimensional (3-D) mesh repair are commonly used methods for the surgical treatment of PSH. However, the efficacy and safety of these surgical techniques have not been adequately compared. Patients with PSH who received 3-D mesh or Sugarbaker repair at our center from August 2012 to May 2023 were included. We retrospectively analyzed their demographic data and postoperative outcomes. The primary outcome measure was the recurrence rate at 1-year follow-up. A total of 86 patients were enrolled, involving 53 in the 3-D mesh (62%) group and 33 in the Sugarbaker (38%) group. Most cases (73%) involved were the laparoscopic approach. The recurrence rate at 1-year follow-up was 15% (eight cases) in the 3-D mesh group and 24% (eight cases) in the Sugarbaker group, with no statistical significance (P = 0.29). Additionally, no differences were observed between the 3-D mesh and Sugarbaker groups in the length of hospitalization or in short- and long-term complications. Sugarbaker and 3-D mesh repair have similar clinical efficacy in the surgical treatment of PSH. Further randomized controlled trials are required to confirm these results. Trial registration number. This study was retrospectively registered at clinicaltrials.gov (NCT06077318).

Four glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been used in children and adolescents with obesity or overweight. This network meta-analysis was conducted to compare the efficacy and safety of these regimens. Embase, PubMed, and Scopus were searched on March 2023 and updated in June 2024 for eligible randomized controlled trials (RCTs). The primary efficacy outcomes were mean difference in actual body weight, BMI (body mass index), BMI z score, and waist circumference. Safety outcomes included nausea, vomiting, diarrhea, abdominal pain, injection-site reaction, and hypoglycemia. Eleven RCTs with 953 participants were eligible. Semaglutide exhibited greater effects in reducing weight, BMI, and BMI z score versus the placebo. Semaglutide was associated with greater weight loss and BMI z score reduction in comparison with exenatide, liraglutide, and dulaglutide. Semaglutide also significantly decreased BMI than exenatide. None of the four GLP-1 RAs were associated with higher risks of diarrhea, headache, and abdominal pain versus the placebo. Liraglutide was more likely to cause nausea, vomiting, hypoglycemia, and injection-site reactions than the placebo. Liraglutide also had higher odds of causing injection-site reactions than other GLP-1 RAs. Semaglutide appeared to be the most effective and safe option among four GLP-1 RAs in children and adolescents with obesity or overweight.

Purpose: Ventral hernia (VH) is a common surgical disease. Previous studies suggested that obesity is an important risk factor for VH. However, the causal relationship between fat distribution and the risk of VH is still unclear. This study used Mendelian randomization (MR) to evaluate their causal relationship.Methods: We used the body mass index (BMI), body fat percentage, and body fat mass to represent general obesity and utilized the volume of abdominal subcutaneous adiposity tissue, visceral adiposity tissue, waist circumference, hip circumference, and waist‐to‐hip ratio to represent abdominal adiposity. The data were extracted from the large‐scale genome‐wide association study of European ancestry. We used two‐sample MR to infer causality, using multivariate MR to correct the effects of confounding factors.Results: Increased BMI, body fat percentage, body fat mass, visceral adiposity tissue, waist circumference, and hip circumference rather than subcutaneous adiposity tissue or waist‐to‐hip ratio, were causally associated with a higher risk of VH. The results of multivariate MR suggested that body fat percentage was causally associated with a higher risk of VH after adjusting for body mass index, diabetes, and smoking.Conclusion: General obesity, increased visceral adiposity tissue, waist circumference, and hip circumference rather than subcutaneous adiposity tissue or the waist‐to‐hip ratio were causally associated with a higher risk of VH. These findings provided a deeper understanding of the role that the distribution of adiposity plays in the mechanism of VH.