Objective Findings from individual anterior cruciate ligament reconstruction (ACLR) registry studies are impactful, but how various registries from different countries compare with different patient populations and surgical techniques has not been described. We sought to describe six ACLR registry cohorts to understand variation across countries. Methods Five European registries and one US registry participated. For each registry, all primary ACLR registered between registry establishment through 31December 2014 were identified. Descriptive statistics included frequencies, proportions, medians and IQRs. Revision incidence rates following primary ACLR were computed. Results 101 125 ACLR were included: 21 820 in Denmark, 300 in Luxembourg, 17 556 in Norway, 30 422 in Sweden, 2972 in the UK and 28 055 in the US. In all six cohorts, males (range: 56.8%–72.4%) and soccer injuries (range: 14.1%–42.3%) were most common. European countries mostly used autografts (range: 93.7%–99.7%); allograft was most common in the US (39.9%). Interference screw was the most frequent femoral fixation in Luxembourg and the US (84.8% and 42.9%), and suspensory fixation was more frequent in the other countries (range: 43.9%–75.5%). Interference was the most frequent tibial fixation type in all six cohorts (range: 64.8%–98.2%). Three-year cumulative revision probabilities ranged from 2.8% to 3.7%. Conclusions Similarities in patient demographics and injury activity were observed between all cohorts of ACLR. However, graft and fixation choices differed. Revision rates were low. This work, including >100 000 ACLR, is the most comprehensive international description of contemporary practice to date.

The phase III RV144 HIV-1 vaccine trial estimated vaccine efficacy (VE) to be 31.2%. This trial demonstrated that the presence of HIV-1–specific IgG-binding Abs to envelope (Env) V1V2 inversely correlated with infection risk, while the presence of Env-specific plasma IgA Abs directly correlated with risk of HIV-1 infection. Moreover, Ab-dependent cellular cytotoxicity responses inversely correlated with risk of infection in vaccine recipients with low IgA; therefore, we hypothesized that vaccine-induced Fc receptor–mediated (FcR-mediated) Ab function is indicative of vaccine protection. We sequenced exons and surrounding areas of FcR-encoding genes and found one FCGR2C tag SNP (rs114945036) that associated with VE against HIV-1 subtype CRF01_AE, with lysine at position 169 (169K) in the V2 loop (CRF01_AE 169K). Individuals carrying CC in this SNP had an estimated VE of 15%, while individuals carrying CT or TT exhibited a VE of 91%. Furthermore, the rs114945036 SNP was highly associated with 3 other FCGR2C SNPs (rs138747765, rs78603008, and rs373013207). Env-specific IgG and IgG3 Abs, IgG avidity, and neutralizing Abs inversely correlated with CRF01_AE 169K HIV-1 infection risk in the CT- or TT-carrying vaccine recipients only. These data suggest a potent role of Fc-γ receptors and Fc-mediated Ab function in conferring protection from transmission risk in the RV144 VE trial.

Importance Consensus guidelines and systematic reviews have suggested that cemented fixation is more effective than uncemented fixation in hemiarthroplasty for displaced femoral neck fractures. Given that these recommendations are based on research performed outside the United States, it is uncertain whether these findings also reflect the US experience. Objective To compare the outcomes associated with cemented vs uncemented hemiarthroplasty in a large US integrated health care system. Design, Setting, and Participants Retrospective cohort study of 12 491 patients aged 60 years and older who underwent hemiarthroplasty treatment of a hip fracture between 2009 and 2017 at 1 of the 36 hospitals owned by Kaiser Permanente, a large US health maintenance organization. Patients were followed up until membership termination, death, or the study end date of December 31, 2017. Exposures Hemiarthroplasty (prosthetic replacement of the femoral head) fixation via bony growth into a porous-coated implant (uncemented) or with cement. Main Outcomes and Measures The primary outcome measure was aseptic revision, defined as any reoperation performed after the index procedure involving exchange of the existing implant for reasons other than infection. Secondary outcomes were mortality (in-hospital, postdischarge, and overall), 90-day medical complications, 90-day emergency department visits, and 90-day unplanned readmissions. Results Among 12 491 patients in the study cohort who underwent hemiarthroplasty for hip fracture (median age, 83 years; 8660 women [69.3%]), 6042 (48.4%) had undergone uncemented fixation and 6449 (51.6%) had undergone cemented fixation, and the median length of follow-up was 3.8 years. In the multivariable regression analysis controlling for confounders, uncemented fixation was associated with a significantly higher risk of aseptic revision (cumulative incidence at 1 year after operation, 3.0% vs 1.3%; absolute difference, 1.7% [95% CI, 1.1%-2.2%]; hazard ratio [HR], 1.77 [95% CI, 1.43-2.19];P < .001). Of the 6 prespecified secondary end points, none showed a statistically significant difference between groups, including in-hospital mortality (1.7% for uncemented fixation vs 2.0% for cemented fixation; HR, 0.94 [95% CI, 0.73-1.21];P = .61) and overall mortality (cumulative incidence at 1 year after operation: 20.0% for uncemented fixation vs 22.8% for cemented fixation; HR, 0.95 [95% CI, 0.90-1.01];P = .08). Conclusions and Relevance Among patients with hip fracture treated with hemiarthroplasty in a large US integrated health care system, uncemented fixation, compared with cemented fixation, was associated with a statistically significantly higher risk of aseptic revision. These findings suggest that US surgeons should consider cemented fixation in the hemiarthroplasty treatment of displaced femoral neck fractures in the absence of contraindications.

Initial studies of 88 transmission pairs in the Zambia Emory HIV Research Project cohort demonstrated that the number of transmitted HLA-B associated polymorphisms in Gag, but not Nef, was negatively correlated to set point viral load (VL) in the newly infected partners. These results suggested that accumulation of CTL escape mutations in Gag might attenuate viral replication and provide a clinical benefit during early stages of infection. Using a novel approach, we have cloned gag sequences isolated from the earliest seroconversion plasma sample from the acutely infected recipient of 149 epidemiologically linked Zambian transmission pairs into a primary isolate, subtype C proviral vector, MJ4. We determined the replicative capacity (RC) of these Gag-MJ4 chimeras by infecting the GXR25 cell line and quantifying virion production in supernatants via a radiolabeled reverse transcriptase assay. We observed a statistically significant positive correlation between RC conferred by the transmitted Gag sequence and set point VL in newly infected individuals (p = 0.02). Furthermore, the RC of Gag-MJ4 chimeras also correlated with the VL of chronically infected donors near the estimated date of infection (p = 0.01), demonstrating that virus replication contributes to VL in both acute and chronic infection. These studies also allowed for the elucidation of novel sites in Gag associated with changes in RC, where rare mutations had the greatest effect on fitness. Although we observed both advantageous and deleterious rare mutations, the latter could point to vulnerable targets in the HIV-1 genome. Importantly, RC correlated significantly (p = 0.029) with the rate of CD4+ T cell decline over the first 3 years of infection in a manner that is partially independent of VL, suggesting that the replication capacity of HIV-1 during the earliest stages of infection is a determinant of pathogenesis beyond what might be expected based on set point VL alone. In the majority of HIV-1 cases, a single virus establishes infection. However, mutations in the viral genome accumulate over time in order to avoid recognition by the host immune response. Certain mutations in the main structural protein, Gag, driven by cytotoxic T lymphocytes are detrimental to viral replication, and we showed previously that, upon transmission, viruses with higher numbers of escape mutations in Gag were associated with lower early set point viral loads. We hypothesized that this could be attributed to attenuation of the transmitted virus. Here, we have cloned the gag gene from 149 newly infected individuals from linked transmission pairs into a clade C proviral vector and determined the replicative capacity in vitro. We found that the replicative capacity conferred by the transmitted Gag correlated with set point viral loads in newly infected individuals, as well as with the viral load of the transmitting partner, and we identified previously unrecognized residues associated with increasing and decreasing replicative capacity. Importantly, we demonstrate that transmitted viruses with high replicative capacity cause more rapid CD4+ decline over the first three years, independent of viral load. This suggests that the trajectory of pathogenesis may be affected very early in infection, before adaptive immunity can respond.