There have been few large studies involving multiethnic cohorts of patients treated with anterior cruciate ligament reconstruction (ACLR), and therefore, little is known about the role that race/ethnicity may play in the differential risk of undergoing revision surgery following primary ACLR. The purpose of this study was to evaluate whether differences exist by race/ethnicity in the risk of undergoing the elective procedure of aseptic revision in a universally insured cohort of patients who had undergone ACLR.This was a retrospective cohort study conducted using our integrated health-care system's ACLR registry and including primary ACLRs from 2008 to 2015. Race/ethnicity was categorized into the following 4 groups: non-Hispanic white, black, Hispanic, and Asian. Multivariable Cox proportional-hazard models were used to evaluate the association between race/ethnicity and revision risk while adjusting for age, sex, highest educational attainment, annual household income, graft type, and geographic region in which the ACLR was performed.Of the 27,258 included patients,13,567 (49.8%) were white, 7,713 (28.3%) were Hispanic, 3,725 (13.7%) were Asian, and 2,253 (8.3%) were black. Asian patients (hazard ratio [HR] = 0.72; 95% confidence interval [CI] = 0.57 to 0.90) and Hispanic patients (HR = 0.83; 95% CI = 0.70 to 0.98) had a lower risk of undergoing revision surgery than did white patients. Within the first 3.5 years postoperatively, we did not observe a difference in revision risk when black patients were compared with white patients (HR = 0.86; 95% CI = 0.64 to 1.14); after 3.5 years postoperatively, black patients had a lower risk of undergoing revision (HR = 0.23; 95% CI = 0.08 to 0.63).In a large, universally insured ACLR cohort with equal access to care, we observed Asian, Hispanic, and black patients to have a similar or lower risk of undergoing elective revision compared with white patients. These findings emphasize the need for additional investigation into barriers to equal access to care. Because of the sensitivity and complexity of race/ethnicity with surgical outcomes, continued assessment into the reasons for the differences observed, as well as any differences in other clinical outcomes, is warranted.Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
The amount of information publicly available from arthroplasty registries is large but could be used more effectively. This project aims to improve the knowledge concerning existing registries to facilitate access, transparency, harmonization, and reporting. Within the International Society of Arthroplasty Registries (ISAR) we aimed at developing, testing, adopting, and making publicly available a short, standardized registry description with items considered relevant for stakeholders using a cross-sectional study survey. Items were chosen based on a literature review and expert advice, selected by 9 ISAR working group members, tested iteratively in 3 registries, and commented upon by 4 external experts. All 29 ISAR member registries as of July 2023 were invited to participate in the project. Included items covered general descriptive information regarding registries, information related to governance, outcomes, data quality, data access, and registry production. The template was adopted, completed, and made publicly available by 25 of the 29 registries. Of those, 2/3 were national registries. 23 captured both hip and knee arthroplasties and 10 captured shoulder arthroplasties. Most registries had public reporting of data quality, methods, and results. Data was accessible in all but 2 registries, mainly as aggregated data. Important items relevant to registry quality for researchers to consistently indicate in scientific papers include scope, inclusion criteria, outcomes definitions, coverage/completeness, and validation processes. This ISAR initiative implemented a short, standardized description to facilitate appropriate use of orthopedic registry data worldwide relevant for a diverse group of stakeholders including researchers, industry, public health and regulatory agencies.
Background: Prior reports of the DePuy Synthes Trochanteric Fixation Nail Advanced (TFNA) revealed a potential mode of fatigue failure at the proximal screw aperture following fixation of extracapsular hip fractures. We sought to compare the revision risk between the TFNA and its prior-generation forebear, the Trochanteric Fixation Nail (TFN). Methods: A retrospective cohort study was performed using data from a U.S. integrated health-care system’s hip fracture registry. The study sample comprised patients who underwent cephalomedullary nail fixation for hip fracture with a TFN (n = 4,007) or TFNA (n = 3,972) from 2014 to 2019. We evaluated the charts and radiographs for patients who underwent any revision. Multivariable Cox regression was used to evaluate the risk of revision related to the index fracture. Results: At the 3-year follow-up, the cumulative probability of revision related to the index fracture was 1.8% for the TFN and 1.9% for the TFNA. After adjustment for covariates, no difference was observed in revision risk (hazard ratio [HR], 1.18 [95% confidence interval (CI), 0.80 to 1.75]; p = 0.40) for the TFNA compared with the TFN. The TFNA was associated with a higher risk of revision for nonunion than the TFN (HR, 1.86 [95% CI, 1.11 to 3.12]; p = 0.018). At the 3-year follow-up, implant breakage was 0.06% for the TFN and 0.2% for the TFNA; with regard to aperture failures related to the index fracture, there were 1 failure for the TFN group and 3 failures for the TFNA group. Conclusions: In a large cohort from a U.S. hip fracture registry, the TFNA had an overall revision rate that was similar to that of the earlier TFN, with implant breakage being a rare revision reason for both groups. Chart and radiographic review found that the TFNA was associated with a higher risk of revision for nonunion. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.
Background Multiple HLA class I alleles have been shown to influence both HIV-1 transmission and viral load. In transmission pairs, viral loads of acutely infected partners correlate with viral loads (VL) of their chronically infected donors. This correlation becomes highly significant after adjustment for host factors known to modulate viral load. In addition, we have previously demonstrated that transmission of a virus containing multiple HLA-I associated polymorphisms resulted in a lower set point VL in Zambian linked recipients. These studies imply that transmitted viral characteristics play a role in defining early HIV-1 pathogenesis, and it will be important for vaccine development to understand which viral characteristics are responsible for this. Methods We investigated the role that the in vitro replicative capacity (RC) of the transmitted Gag plays in defining HIV-1 clinical parameters, by cloning gag genes from the founder virus in newly infected partners of 149 epidemiologically linked transmission pairs i nto the subtype C, R5 tropic MJ4 provirus. Results We observed a statistically significant positive correlation between the RC of Gag-MJ4 chimeras and set point VL in seroconverters (P=0.013). The RC of the transmitted Gag also correlated (P=0.025) to the viral load in the chronically infected donor, pointing to RC as the major viral characteristic responsible for the link between donor and linked recipient viral loads. The long term clinical benefit associated with the transmission of attenuated viruses was investigated by performing a Kaplan Meier analysis of time to CD4+ count less than 350. Individuals infected with attenuated gag sequences (RC 2) replicating viruses (P = 0.034).
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.
Several genome-wide association studies (GWAS) have associated variants in late-onset Alzheimer disease (LOAD) susceptibility genes; however, these single nucleotide polymorphisms (SNPs) have very modest effects, suggesting that single SNP approaches may be inadequate to identify genetic risks. An alternative approach is the use of multilocus genotype patterns (MLGPs) that combine SNPs at different susceptibility genes.Using data from 1,365 subjects in the National Institute on Aging Late-Onset Alzheimer's Disease Family Study, we conducted a family-based association study in which we tabulated MLGPs for SNPs at CR1, BIN1, CLU, PICALM, and APOE. We used generalized estimating equations to model episodic memory as the dependent endophenotype of LOAD and the MLGPs as predictors while adjusting for sex, age, and education.Several genotype patterns influenced episodic memory performance. A pattern that included PICALM and CLU was the strongest genotypic profile for lower memory performance (β = -0.32, SE = 0.19, p = 0.021). The effect was stronger after addition of APOE (p = 0.016). Two additional patterns involving PICALM, CR1, and APOE and another pattern involving PICALM, BIN1, and APOE were also associated with significantly poorer memory performance (β = -0.44, SE = 0.09, p = 0.009 and β = -0.29, SE = 0.07, p = 0.012) even after exclusion of patients with LOAD. We also identified genotype pattern involving variants in PICALM, CLU, and APOE as a predictor of better memory performance (β = 0.26, SE = 0.10, p = 0.010).MLGPs provide an alternative analytical approach to predict an individual's genetic risk for episodic memory performance, a surrogate indicator of LOAD. Identifying genotypic patterns contributing to the decline of an individual's cognitive performance may be a critical step along the road to preclinical detection of Alzheimer disease.
