Female sex and ipsilateral reoperation risk following mesh-based inguinal hernia repair: a cohort study including 131,626 repairs in adults from an integrated healthcare system over a 10-year period.

PURPOSE: We sought to compare females and males for the risk of reoperation following different inguinal hernia repair approaches (open, laparoscopic, and robotic). METHODS: We conducted a retrospective cohort study including all patients aged ≥ 18 who underwent first inguinal hernia repair with mesh within a US integrated healthcare system (2010-2020). Data were obtained from the system's integrated electronic health record. Multiple Cox proportional-hazards regression was used to evaluate the association between sex and risk for ipsilateral reoperation during follow-up. Analysis was stratified by surgical approach (open, laparoscopic, and robotic). RESULTS: The study cohort was comprised of 110,805 patients who underwent 131,626 inguinal hernia repairs with mesh, 10,079 (7.7%) repairs were in females. After adjustment for confounders, females had a higher risk of reoperation than males following open groin hernia repair (hazard ratio [HR] = 1.98, 95% CI 1.74-2.25), but a lower reoperation risk following laparoscopic repair (HR = 0.70, 95% CI 0.51-0.97). The crude 5-year cumulative reoperation probability following robotic repair was 2.8% in males and no reoperations were observed for females. Of females who had a reoperation, 10.3% (39/378) were for a femoral hernia, while only 0.6% (18/3110) were for femoral hernias in males. CONCLUSION: In a large multi-center cohort of mesh-based inguinal hernia repair patients, we found a higher risk for reoperation in females after an open repair approach compared to males. Lower risk was observed for females through a minimally invasive approach (laparoscopic or robotic) and may be due to the ability to identify an occult femoral hernia through these approaches.

Risk factors for reoperation following inguinal hernia repair: results from a cohort of patients from an integrated healthcare system.

PURPOSE: Inguinal hernia repair is one of the most common operations performed globally. Identification of risk factors that contribute to hernia recurrence following an index inguinal hernia repair, especially those that are modifiable, is of paramount importance. Therefore, we sought to investigate risk factors for reoperation following index inguinal hernia repair. METHODS: 125,133 patients aged ≥ 18 years who underwent their first inguinal hernia repair with mesh within a large US integrated healthcare system were identified for a cohort study (2010-2020). Laparoscopic, robotic, and open procedures were included. The system's integrated electronic health record was used to obtain data on demographics, patient characteristics, surgical characteristics, and reoperations. The association of these characteristics with ipsilateral reoperation during follow-up was modeled using Cox proportional-hazards regression. Risk factors were selected into the final model by stepwise regression with Akaike Information Criteria, which quantifies the amount of information lost if a factor is left out of the model. Factors associated with reoperation with p < 0.05 were considered statistically significant. RESULTS: The cumulative incidence of reoperation at 5-year follow-up was 2.4% (95% CI 2.3-2.5). Increasing age, female gender, increasing body mass index, White race, chronic pulmonary disease, diabetes, drug abuse, peripheral vascular disease, and bilateral procedures all associated with a higher risk for reoperation during follow-up. CONCLUSION: This study identifies several risk factors associated with reoperation following inguinal hernia repair. These risk factors may serve as targets for optimization protocols prior to elective inguinal hernia repair, with the goal of reducing reoperation risk.

Mesh-based inguinal hernia repairs in an integrated healthcare system and surgeon and hospital volume: a cohort study of 110,808 patients from over a decade.

PURPOSE: The aim of this study was to describe a cohort of patients who underwent inguinal hernia repair within a United States-based integrated healthcare system (IHS) and evaluate the risk for postoperative events by surgeon and hospital volume within each surgical approach, open, laparoscopic, and robotic. METHODS: Patients aged ≥ 18 years who underwent their first inguinal hernia repair were identified for a cohort study (2010-2020). Average annual surgeon and hospital volume were broken into quartiles with the lowest volume quartile as the reference group. Multiple Cox regression evaluated risk for ipsilateral reoperation following repair by volume. All analyses were stratified by surgical approach (open, laparoscopic, and robotic). RESULTS: 110,808 patients underwent 131,629 inguinal hernia repairs during the study years; procedures were performed by 897 surgeons at 36 hospitals. Most repairs were open (65.4%), followed by laparoscopic (33.5%) and robotic (1.1%). Reoperation rates at 5 and 10 years of follow-up were 2.4% and 3.4%, respectively; rates were similar across surgical groups. In adjusted analysis, surgeons with higher laparoscopic volumes had a lower reoperation risk (27-46 average annual repairs: hazard ratio [HR] = 0.63, 95% confidence interval [CI] 0.53-0.74; ≥ 47 repairs: HR 0.53, 95% CI 0.44-0.64) compared to those in the lowest volume quartile (< 14 average annual repairs). No differences in reoperation rates were observed in reference to surgeon or hospital volume following open or robotic inguinal hernia repair. CONCLUSION: High-volume surgeons may reduce reoperation risk following laparoscopic inguinal hernia repair. We hope to better identify additional risk factors for inguinal hernia repair complications and improve patient outcomes with future studies.

HLA class II diversity in HIV-1 uninfected individuals from the placebo arm of the RV144 Thai vaccine efficacy trial.

The RV144 HIV vaccine trial in Thailand elicited antibody responses to the envelope of HIV-1, which correlated significantly with the risk of HIV-1 acquisition. Human leukocyte antigen (HLA) class II molecules are essential in antigen presentation to CD4 T cells for activation of B cells to produce antibodies. We genotyped the classical HLA-DRB1, DQB1, and DPB1 genes in 450 individuals from the placebo arm of the RV144 study to determine the background allele and haplotype frequencies of these genes in this cohort. High-resolution 4 and 6-digit class II HLA typing data was generated using sequencing-based methods. The observed diversity for the HLA loci was 33 HLA-DRB1, 15 HLA-DQB1, and 26 HLA-DPB1 alleles. Common alleles with frequencies greater than 10% were DRB1*07:01, DRB1*09:01, DRB1*12:02, DRB1*15:02, DQB1*02:01/02, DQB1*03:01, DQB1*03:03, DQB1*05:01, DQB1*05:02, DPB1*04:01:01, DPB1*05:01:01, and DPB1*13:01:01. We identified 28 rare alleles with frequencies of less than 1% in the Thai individuals. Ambiguity for HLA-DPB1*28:01 in exon 2 was resolved to DPB1*296:01 by next-generation sequencing of all exons. Multi-locus haplotypes including HLA class I and II loci were reported in this study. This is the first comprehensive report of allele and haplotype frequencies of all three HLA class II genes from a Thai population. A high-resolution genotyping method such as next-generation sequencing avoids missing rare alleles and resolves ambiguous calls. The HLA class II genotyping data generated in this study will be beneficial not only for future disease association/vaccine efficacy studies related to the RV144 study, but also for similar studies in other diseases in the Thai population, as well as population genetics and transplantation studies.

Immunogenetic influences on acquisition of HIV-1 infection: consensus findings from two African cohorts point to an enhancer element in IL19 (1q32.2).

Numerous reports have suggested that immunogenetic factors may influence human immunodeficiency virus (HIV)-1 acquisition, yet replicated findings that translate between study cohorts remain elusive. Our work aimed to test several hypotheses about genetic variants within the IL10-IL24 gene cluster that encodes interleukin (IL)-10, IL-19, IL-20 and IL-24. In aggregated data from 515 Rwandans and 762 Zambians with up to 12 years of follow-up, 190 single-nucleotide polymorphisms passed quality control procedures. When HIV-1-exposed seronegative subjects (n=486) were compared with newly seroconverted individuals (n=313) and seroprevalent subjects (n=478) who were already infected at enrollment, rs12407485 (G>A) in IL19 showed a robust association signal in adjusted logistic regression models (odds ratio=0.64, P=1.7 × 10(-4) and q=0.033). Sensitivity analyses demonstrated that (i) results from both cohorts and subgroups within each cohort were highly consistent; (ii) verification of HIV-1 infection status after enrollment was critical; and (iii) supporting evidence was readily obtained from Cox proportional hazards models. Data from public databases indicate that rs12407485 is part of an enhancer element for three transcription factors. Overall, these findings suggest that molecular features at the IL19 locus may modestly alter the establishment of HIV-1 infection.

Host genetics and immune control of HIV-1 infection: fine mapping for the extended human MHC region in an African cohort.

Multiple major histocompatibility complex (MHC) loci encoding human leukocyte antigens (HLA) have allelic variants unequivocally associated with differential immune control of HIV-1 infection. Fine mapping based on single nucleotide polymorphisms (SNPs) in the extended MHC (xMHC) region is expected to reveal causal or novel factors and to justify a search for functional mechanisms. We have tested the utility of a custom fine-mapping platform (the ImmunoChip) for 172 HIV-1 seroconverters (SCs) and 449 seroprevalent individuals (SPs) from Lusaka, Zambia, with a focus on more than 6400 informative xMHC SNPs. When conditioned on HLA and nongenetic factors previously associated with HIV-1 viral load (VL) in the study cohort, penalized approaches (HyperLasso models) identified an intergenic SNP (rs3094626 between RPP21 and HLA-E) and an intronic SNP (rs3134931 in NOTCH4) as novel correlates of early set-point VL in SCs. The minor allele of rs2857114 (downstream from HLA-DOB) was an unfavorable factor in SPs. Joint models based on demographic features, HLA alleles and the newly identified SNP variants could explain 29% and 15% of VL variance in SCs and SPs, respectively. These findings and bioinformatics strongly suggest that both classic and nonclassic MHC genes deserve further investigation, especially in Africans with relatively short haplotype blocks.