Immune and behavioral correlates of protection against symptomatic post-vaccination SARS-CoV-2 infection.

Introduction: We sought to determine pre-infection correlates of protection against SARS-CoV-2 post-vaccine inzfections (PVI) acquired during the first Omicron wave in the United States. Methods: Serum and saliva samples from 176 vaccinated adults were collected from October to December of 2021, immediately before the Omicron wave, and assessed for SARS-CoV-2 Spike-specific IgG and IgA binding antibodies (bAb). Sera were also assessed for bAb using commercial assays, and for neutralization activity against several SARS-CoV-2 variants. PVI duration and severity, as well as risk and precautionary behaviors, were assessed by questionnaires. Results: Serum anti-Spike IgG levels assessed by research assay, neutralization titers against Omicron subvariants, and low home risk scores correlated with protection against PVIs after multivariable regression analysis. Commercial assays did not perform as well as research assay, likely due to their lower dynamic range. Discussion: In the 32 participants that developed PVI, anti-Spike IgG bAbs correlated with lower disease severity and shorter duration of illness.

The role of iliopsoas fractional lengthening in hip arthroscopy: a systematic review.

Arthroscopic iliopsoas fractional lengthening (IFL) is a surgical option for the treatment of internal snapping hip syndrome (ISHS) after failing conservative management. Systematic review. A search of PubMed central, National Library of Medicine (MEDLINE) and Scopus databases were performed by two individuals from the date of inception to April 2023. Inclusion criteria were ISHS treated with arthroscopy. Sample size, patient-reported outcomes and complications were recorded for 24 selected papers. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed and registered on PROSPERO database for systematic reviews (CRD42023427466). Thirteen retrospective case series, ten retrospective comparative studies, and one randomized control trial from 2005 to 2022 were reported on 1021 patients who received an iliopsoas fractional lengthening. The extracted data included patient satisfaction, visual analogue scale, the modified Harris hip score and additional outcome measures. All 24 papers reported statistically significant improvements in post-operative patient-reported outcome measures after primary hip arthroscopy and iliopsoas fractional lengthening. However, none of the comparative studies found a statistical benefit in performing IFL. Existing studies lack conclusive evidence on the benefits of Iliopsoas Fractional Lengthening (IFL), especially for competitive athletes, individuals with Femoroacetabular Impingement (FAI), and borderline hip dysplasia. Some research suggests IFL may be a safe addition to hip arthroscopy for Internal Snapping Hip Syndrome, but more comprehensive investigations are needed. Future studies should distinguish between concurrent procedures and develop methods to determine if the psoas muscle is the source of pain, instead of solely attributing it to the joint.

Small bowel perforation due to ingested frog bone: a case report.

Perforation of the gastrointestinal tract by ingested foreign body is an uncommon surgical emergency, most typically associated with the consumption of fish and chicken bones. We present an unusual case of a gentleman presenting emergently with an acute abdomen following ingestion of a meal containing frog meat. Emergent computed tomography (CT) revealed findings suggestive of jejunal perforation due to a foreign body. At laparotomy, a mid-jejunal site of perforation was noted due to a protruding piece of fractured frog bone. Washout and primary repair of the small bowel enterotomy were performed, and the patient made an excellent post-operative recovery.

Surgical management of recurrent instability following Latarjet procedure - A systematic review of salvage procedures.

Background: Failed Latarjet procedures pose a surgical challenge due to complex anatomical issues. This systematic review investigates salvage techniques for recurrent instability following a Latarjet procedure. Methods: A search was conducted on MEDLINE and PubMed Central following the methodology registered to International Prospective Register of Systematic Reviews. Inclusion criteria focused on identifying revision procedures following a Latarjet procedure. Exclusion criteria filtered out irrelevant studies, such as those focused on Bankart procedures. After a multistage selection process, 10 eligible studies were included for data extraction. Results: The most frequently utilized technique for salvage was variations of the Eden-Hybinette procedure. Complications associated with these salvage procedures include graft-related problems and donor site morbidity. Patients reported significant improvements in multiple patient-reported outcome scores, and multiple studies indicated high rates of return to sports activities. However, it is noteworthy that there remains an average recurrence rate of 7%. Discussion: The review emphasizes the limited therapeutic options available largely due to shoulder anatomy alterations. Despite promising trends in patient-reported outcomes, recurrence remains possible post-salvage surgeries. Conclusion: Addressing recurrent instability after a Latarjet procedure continues to be a unique surgical challenge. However, this systematic review highlights encouraging indications, with positive trends evident in patient-reported outcomes.

Innate immune cell activation after HIV-1 vaccine administration is associated with increased antibody production.

The RV144 Thai phase III clinical trial's canarypox-protein HIV vaccine regimen showed modest efficacy in reducing infection. We therefore sought to determine the effects of vaccine administration on innate cell activation and subsequent associations with vaccine-induced immune responses. RV306 was a randomized, double-blind clinical trial in HIV-uninfected Thai adults that tested delayed boosting following the RV144 regimen. PBMC collected from RV306 participants prior to and 3 days after the last boost were used to investigate innate immune cell activation. Our analysis showed an increase in CD38+ mucosal associated invariant T (MAIT) cells, CD38+ invariant natural killer T (iNKT) cells, CD38+ γδ T cells, CD38+, CD69+ and HLA-DR+ NK cells 3 days after vaccine administration. An increase in CD14-CD16+ non-classical monocytes and CD14+CD16+ intermediate monocytes accompanied by a decrease in CD14+CD16- classical monocytes was also associated with vaccine administration. Inclusion of ALVAC-HIV in the boost did not further increase MAIT, iNKT, γδ T, and NK cell activation or increase the proportion of non-classical monocytes. Additionally, NK cell activation 3 days after vaccination was positively associated with antibody titers of HIV Env-specific total IgG and IgG1. Vδ1 T cell activation 3 days after vaccine administration was associated with HIV Env-specific IgG3 titers. Finally, we observed trending associations between MAIT cell activation and Env-specific IgG3 titers and between NK cell activation and TH023 pseudovirus neutralization titers. Our study identifies a potential role for innate cells, specifically NK, MAIT, and γδ T cells, in promoting antibody responses following HIV-1 vaccine administration.

Systematic Review of Bracing After Proximal Hamstring Repair.

Background: Traditionally, postoperative rehabilitation protocols after proximal hamstring repair (PHR) for avulsion of the proximal hamstring tendon from its ischial insertion recommend bracing the hip and/or knee to protect the fixation. However, because of the cumbersome nature of these orthoses, recent studies have investigated outcomes in patients with postoperative protocols that do not include any form of postoperative bracing. Purpose: To synthesize the current body of evidence concerning bracing versus nonbracing postoperative management of PHR. Study Design: Systematic review; level of evidence, 4. Methods: Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we conducted a thorough search of the PubMed/Medline, Cochrane, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Embase (OVID) databases on March 24, 2023. We analyzed complication rates, reoperation rates, patient satisfaction, return to sport, and patient-reported outcomes of studies that used postoperative bracing versus studies that used no postoperative bracing after PHR with at least 12 months of follow-up. A total of 308 articles were identified after initial search. Results: In total, 25 studies were included in this review: 18 studies (905 patients) on bracing and 7 studies (291 patients) on nonbracing after PHR. The overall complication rate in the braced patients was found to be 10.9%, compared with 12.7% in nonbraced patients. The rate of reoperation due to retear of the proximal hamstring was found to be 0.05% in braced patients and 3.1% in nonbraced patients. Patient-reported outcome measures were found to be higher at the final follow-up in braced versus nonbraced patients, and patient satisfaction was found to be 94.7% in braced studies compared with 88.9% in nonbraced studies. The rate of 12-month return to sport in athletic patients was 88.4% with bracing and 82.7% without bracing. Conclusion: The findings of this review demonstrated lower complication and reoperation rates, higher patient-reported outcome scores, higher patient satisfaction, and a higher rate of return to sport in braced patients compared with nonbraced patients.

Reverse Shoulder Arthroplasty for Irreparable Rotator Cuff Tear After Radial to Axillary End-to-Side Transfer: A Case Report.

CASE: A 60-year-old man sustained a massive irreparable rotator cuff tear and axillary nerve palsy with deltoid dysfunction after an anterior shoulder dislocation. He underwent staged reverse end-to-side radial-to-axillary nerve transfer with return of deltoid function allowing for subsequent reverse shoulder arthroplasty. At 1 year postoperatively, he returned to full activity. CONCLUSION: Irreparable rotator cuff tears complicated by axillary nerve palsy can be effectively treated with a staged approach of nerve transfer followed by reverse shoulder arthroplasty.

Effects of Vitamin D Supplementation in Elite Athletes: A Systematic Review.

Background: Deficiency in vitamin D has been shown to increase the risk of injury. Purpose: To synthesize current placebo-controlled randomized trials investigating the effect of vitamin D supplementation in elite athletes on (1) aerobic capacity; (2) anaerobic measures, such as strength, speed, and anaerobic power; (3) serum biomarkers of inflammation; and (4) bone health. Study Design: Systematic review; Level of evidence, 1. Methods: A literature search was conducted on November 30, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included were randomized, placebo-controlled studies of longer than 2 weeks on subjects with active participation in organized sport. Excluded were nonrandomized controlled trial study designs, vitamin D administration routes other than oral, studies that did not use vitamin D supplementation as the sole intervention, and studies with nonathletic or military populations. Results: Out of 2331 initial studies, 14 studies (482 athletes) were included. Of the 3 studies that assessed aerobic capacity, 2 demonstrated significantly greater improvements in maximal oxygen uptake and physical working capacity-170 (P < .05) in supplemented versus nonsupplemented athletes. Measurements of anaerobic power and strength were consistently increased in supplemented groups compared with nonsupplemented groups in 5 out of the 7 studies that assessed this. Of the 6 studies that assessed sprint speed, 4 found no significant difference between supplemented and nonsupplemented groups. Aside from 1 study that found significantly lower interleukin-6 levels in supplemented athletes, measures of other inflammatory cytokines were not affected consistently by supplementation. The 4 studies that assessed markers of bone health were conflicting regarding benefits of supplementation. One study found demonstrated improvements in bone mineral density in response to supplementation (P = .02) compared with control whereas another found no significant difference between supplemented and nonsupplemented groups. However, in 3 other studies, serum biomarkers of bone turnover such as bone-specific alkaline phosphatase, parathyroid hormone, and N-terminal telopeptide appeared to be higher in subjects with lower serum vitamin D levels (P < .05). Conclusion: Results of this systematic review indicated that the greatest benefit of vitamin D supplementation in elite athletes may be improving aerobic endurance, anaerobic power, and strength. More research is needed to determine the effect of vitamin D supplementation on bone health and injury risk in this population.

Significant Increase in Early Reoperation After Latarjet-Bristow Procedure Versus Arthroscopic Bankart Repair for Anterior Shoulder Instability: A Propensity-Score Matched Analysis.

PURPOSE: To compare the 30-day outcomes, including length of stay, short-term complications, hospital readmission, all-cause reoperation, and death after arthroscopic Bankart (AB) and Latarjet. METHODS: Patients in the National Surgical Quality Improvement Program database who had undergone either AB or Latarjet-Bristow (LB) procedures for anterior shoulder instability from 2012 to 2018 were identified using Current Procedural Terminology codes. Nearest neighbor propensity score matching was used to address any potential demographic differences. The 30-day incidence of postoperative complications were compared, and univariate and multivariate logistic regressions were used to identify risk factors associated with the incidence of post-operative complications. RESULTS: A total of 7,519 patients were identified, with 6,990 (93.0%) undergoing AB and 529 (7.0%) LB. After propensity score matching, the baseline demographics were not significantly different (P > .05). There was no significant difference in rate of total adverse events between the AB and LB cohorts (P = .06). There was a significant difference in the rate of return to the operating room between LB (1.9%) when compared to AB (0%) (P < .001). Of reoperations, 40% were due to need for revision stabilization (0.8% of all LB cases) and 40% were for irrigation and debridement. There was also a significant difference in operative time (AB = 87 minutes, LB = 131 minutes; P < .0001). CONCLUSIONS: Overall 30-day complication rates were low for both groups, with similar rates among AB and LB patients. However, there was a statistically significant increased rate of short-term reoperation or revision stabilization in the LB cohort. LEVEL OF EVIDENCE: Level III, retrospective comparative prognostic trial.

Decreased Self-reported Physical Fitness Following SARS-CoV-2 Infection and the Impact of Vaccine Boosters in a Cohort Study.

Background: The long-term effects of coronavirus disease 2019 (COVID-19) on physical fitness are unclear, and the impact of vaccination on that relationship is uncertain. Methods: We compared survey responses in a 1-year study of US military service members with (n = 1923) and without (n = 1591) a history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We fit Poisson regression models to estimate the association between history of SARS-CoV-2 infection and fitness impairment, adjusting for time since infection, demographics, and baseline health. Results: The participants in this analysis were primarily young adults aged 18-39 years (75%), and 71.5% were male. Participants with a history of SARS-CoV-2 infection were more likely to report difficulty exercising (38.7% vs 18.4%; P < .01), difficulty performing daily activities (30.4% vs 12.7%; P < .01), and decreased fitness test (FT) scores (42.7% vs 26.2%; P < .01) than those without a history of infection. SARS-CoV-2-infected participants were at higher risk of these outcomes after adjusting for other factors (unvaccinated: exercising: adjusted risk ratio [aRR], 3.99; 95% CI, 3.36-4.73; activities: aRR, 5.02; 95% CI, 4.09-6.16; FT affected: aRR, 2.55; 95% CI, 2.19-2.98). Among SARS-CoV-2-positive participants, full vaccination before infection was associated with a lower risk of post-COVID-19 fitness impairment (fully vaccinated: exercise: aRR, 0.81; 95% CI, 0.70-0.95; activities: aRR, 0.76; 95% CI, 0.64-0.91; FT: aRR, 0.87; 95% CI, 0.76-1.00; boosted: exercise: aRR, 0.62; 95% CI, 0.51-0.74; activities: aRR, 0.52; 95% CI, 0.41-0.65; FT: aRR, 0.59; 95% CI, 0.49-0.70). Conclusions: In this study of generally young, healthy military service members, SARS-CoV-2 infection was associated with lower self-reported fitness and exercise capacity; vaccination and boosting were associated with lower risk of self-reported fitness loss.

Increased Age, Operative Time, American Society of Anesthesiologists Classification, Functional Dependency, and Comorbidity Burden Are Risk Factors for Adverse Events After Meniscectomy and Meniscus Repair: 10-Year Analysis of 64,223 Patients.

PURPOSE: To use the National Surgical Quality Improvement Program (NSQIP) database to identify risk factors for 30-day adverse events and hospital readmission following isolated and unilateral meniscectomy or meniscus repair. METHODS: A retrospective review of the NSQIP database from the years 2012 to 2021 identified all patients undergoing isolated, unilateral meniscectomy or meniscus repair. Multivariable analyses were performed for each procedure to identify patient characteristics associated with any adverse event (AAE) or unplanned hospital readmission within 30 days of surgery. RESULTS: From 2012 to 2021, 59,450 (93%) patients underwent meniscectomy, and 4,773 (7%) patients underwent meniscus repair. Overall adverse event rate was 0.95% after meniscectomy and 1.40% after repair. Risk factors for AAE after meniscectomy included increased age (odds ratio [OR] = 1.010; P = .009), increased operative time (OR = 1.003; P = 0.011), American Society of Anesthesiologists (ASA) class IV (OR = 2.048; P = .045), functional dependency (OR = 3.527; P = .001), and current smoking (OR = 1.308; P = .018). Risk factors for AAE after meniscus repair included age (OR = 1.024; P = .016), operative time (OR = 1.004; P = .038), and bleeding disorders (OR = 7.000; P = .014). ASA class III increased risk of hospital readmission after both procedures (OR = 1.906; P = .008; OR = 4.101; P = .038), and medical comorbidities of heart failure (OR = 3.924; P = .016), hypertension (OR = 1.412; P = .011), and chronic obstructive pulmonary disease (OR = 2.350; P < .001) increased readmission risk after meniscectomy only. CONCLUSIONS: Per analysis of the ACS-NSQIP database, surgical treatment of meniscal tears in the knee has been performed frequently over the past 10 years, with meniscectomies comprising over 90% of cases. Increased age and operative time were associated with a modest risk of adverse events after both meniscectomy and meniscus repair. Increased comorbidity burden, evidenced by ASA class, dependent functional status, current smoking, and systemic medical conditions, such as heart failure, hypertension, chronic obstructive pulmonary disease, and bleeding disorders, greatly increased rates of unfavorable outcomes within 30 days of meniscus surgery. LEVEL OF EVIDENCE: Level III, retrospective prognostic comparative investigation.

The Impact of Infectious Disease Syndromes on Activities During Military Travel.

Background: We evaluated the impact of infectious disease (ID) syndromes on US active duty (AD) servicemembers returning from overseas deployment (DEP), military training exercises (EXR), or short-term military travel (eg, temporary assignment of duty [TDY]). Methods: We conducted a survey-based assessment of US AD servicemembers returning from DEP, EXR, or TDY between 2015 and 2019. Subjects completed a post-travel survey capturing symptoms of travelers' diarrhea (TD), influenza-like illness (ILI), and febrile illness (FI). Risk factors associated with any ID syndrome (ie, either TD, ILI, or FI) that impacted daily activities were assessed using a logistic regression model with backward selection. Results: One-third of servicemembers (654/1822) experienced an ID syndrome, and 26% (471/1822) reported a ≥50% reduction in activity level due to an ID syndrome (median duration, 3 days). TD was the most common ID syndrome experienced and accounted for 73% (346/471) of ID syndromes impacting daily activities. The greatest impact of ID syndromes was observed in servicemembers on DEP. Compared with servicemembers on EXR or TDY, those on DEP had a longer duration of travel and a delayed period of risk for ID syndromes. Multivariate analysis identified high-risk exposures (ie, environmental exposures, close contact with locals, consuming food from street vendors) and behaviors (ie, inability to sanitize hands before meals) that could be used to inform mitigation strategies. Conclusions: ID syndromes result in a significant loss of productivity during military travel. Addressing modifiable risk factors and access to TD self-treatment in high-risk settings may help mitigate the impact of ID threats during military travel.

Natural killer cells and BNT162b2 mRNA vaccine reactogenicity and durability.

Introduction: Natural killer (NK) cells can both amplify and regulate immune responses to vaccination. Studies in humans and animals have observed NK cell activation within days after mRNA vaccination. In this study, we sought to determine if baseline NK cell frequencies, phenotype, or function correlate with antibody responses or inflammatory side effects induced by the Pfizer-BioNTech COVID-19 vaccine (BNT162b2). Methods: We analyzed serum and peripheral blood mononuclear cells (PBMCs) from 188 participants in the Prospective Assessment of SARS-CoV-2 Seroconversion study, an observational study evaluating immune responses in healthcare workers. Baseline serum samples and PBMCs were collected from all participants prior to any SARS-CoV-2 infection or vaccination. Spike-specific IgG antibodies were quantified at one and six months post-vaccination by microsphere-based multiplex immunoassay. NK cell frequencies and phenotypes were assessed on pre-vaccination PBMCs from all participants by multi-color flow cytometry, and on a subset of participants at time points after the 1st and 2nd doses of BNT162b2. Inflammatory side effects were assessed by structured symptom questionnaires, and baseline NK cell functionality was quantified by an in vitro killing assay on participants that reported high or low post-vaccination symptom scores. Results: Key observations include: 1) circulating NK cells exhibit evidence of activation in the week following vaccination, 2) individuals with high symptom scores after 1st vaccination had higher pre-vaccination NK cytotoxicity indices, 3) high pre-vaccination NK cell numbers were associated with lower spike-specific IgG levels six months after two BNT162b2 doses, and 4) expression of the inhibitory marker NKG2A on immature NK cells was associated with higher antibody responses 1 and 6 months post-vaccination. Discussion: These results suggest that NK cell activation by BNT162b2 vaccination may contribute to vaccine-induced inflammatory symptoms and reduce durability of vaccine-induced antibody responses.

Metabolic phenotypes reflect patient sex and injury status: A cross-sectional analysis of human synovial fluid.

OBJECTIVE: Osteoarthritis is a heterogeneous disease. The objective was to compare differences in underlying cellular mechanisms and endogenous repair pathways between synovial fluid (SF) from male and female participants with different injuries to improve the current understanding of the pathophysiology of downstream post-traumatic osteoarthritis (PTOA). DESIGN: SF from n = 33 knee arthroscopy patients between 18 and 70 years with no prior knee injuries was obtained pre-procedure and injury pathology assigned post-procedure. SF was extracted and analyzed via liquid chromatography-mass spectrometry metabolomic profiling to examine differences in metabolism between injury pathologies (ligament, meniscal, and combined ligament and meniscal) and patient sex. Samples were pooled and underwent secondary fragmentation to identify metabolites. RESULTS: Different knee injuries uniquely altered SF metabolites and downstream pathways including amino acid, lipid, and inflammatory-associated metabolic pathways. Notably, sexual dimorphic metabolic phenotypes were examined between males and females and within injury pathology. Cervonyl carnitine and other identified metabolites differed in concentrations between sexes. CONCLUSIONS: These results suggest that different injuries and patient sex are associated with distinct metabolic phenotypes. Considering these phenotypic associations, a greater understanding of metabolic mechanisms associated with specific injuries, sex, and PTOA development may yield data regarding how endogenous repair pathways differ between male and female injury types. Ongoing metabolomic analysis of SF in injured male and female patients can be performed to monitor PTOA development and progression.

Unique HIV Risk Factors and Prevention Needs for Transgender Women and Cisgender Men Who Have Sex with Men in Bangkok, Thailand.

Background: Transgender women (TGW) and cisgender men who have sex with men (cis-MSM) are often grouped together as key populations. We evaluated behavioral and other characteristics that may distinguish TGW from cis-MSM in Bangkok, Thailand. Methods: We enrolled into an 18-month cohort cis-MSM and TGW 18-35 years of age without HIV, who reported anal intercourse plus condomless anal intercourse, multiple partners, transactional sex, and/or sexually transmitted infection. Robust multivariable Poisson regression was used to estimate adjusted prevalence ratios (aPRs) and confidence intervals (95% CIs) for associations with being a TGW. Among TGW, logistic regression with generalized estimating equations was used to estimate adjusted odds ratios (aORs) and 95% CIs for associations with taking hormones and having undergone gender affirmation surgery (GAS). Results: From 2017 to 2019, 660 cis-MSM and 348 TGW were enrolled. Compared to cis-MSM, TGW were more likely to be attracted to mostly/only men (aPR: 3.79, 95% CI: 1.57-9.13), have a higher monthly income (aPR: 1.25, 95% CI: 1.04-1.50), have lived in their current residence for <1 year (aPR: 1.21, 95% CI: 1.01-1.46), have engaged in sex work (aPR: 1.48, 95% CI: 1.23-1.77), and be less likely to have ever undergone HIV testing (aPR: 0.83, 95% CI: 0.70-0.98). Among TGW, 149 (42.8%) were taking hormones and 33 (9.5%) had undergone GAS. GAS was more common among TGW who ever used methamphetamines (aOR: 1.55, 95% CI: 1.00-2.41) and those >23 years (18-20-year olds aOR: 0.17, 95% CI: 0.05-0.55; 21-23-year olds aOR: 0.36, 95% CI: 0.20-0.65). Conclusions: TGW and cis-MSM are unique populations; tailored, gender-affirming, differentiated models of HIV prevention and care are necessary to address vulnerabilities specific to each key population.

Surgical Management and Return to Activity of an Athlete with Traumatic Posterior Tibial Tendon Rupture and Associated Injuries: A Case Report.

CASE: A 22-year-old athlete sustained a traumatic posterior tibial tendon (PTT) rupture with medial malleolus fracture and anterior tibial plafond chondral lesion during practice. He underwent PTT repair, ankle arthroscopy with microfracture, and medial malleolus open reduction and internal fixation with deltoid ligament repair. At 1 year postoperatively, the patient returned to activity excluding high-level competition. CONCLUSION: Anterior tibial chondral impaction injury with an avulsion fracture of the medial malleolus and PTT tear is effectively treated with a combined arthroscopic and open approach.

Additional boosting to the RV144 vaccine regimen increased Fc-mediated effector function magnitude but not durability.

OBJECTIVES: The RV144 vaccine trial resulted in a decreased risk of HIV acquisition that was associated with a nonneutralizing antibody response. The objective of this study was to determine the impact of an additional boost to the RV144 vaccine regimen on antibody effector function and durability. DESIGN: RV306 was a randomized, double-blind late boosting of the RV144 prime-boost regimen in HIV-uninfected Thai adults (NCT01931358). This analysis included study participants who received the RV144 vaccine regimen and received no additional boost (group 1) or were boosted with ALVAC-HIV and AIDSVAX (group 2) or only AIDSVAX alone (group 3) 24 weeks after completing the RV144 series. METHODS: Plasma samples from RV306 study participants were used to measure antibody-dependent cellular phagocytosis (ADCP), antibody-dependent neutrophil phagocytosis (ADNP), antibody-dependent complement deposition (ADCD), antibody-dependent cellular cytotoxicity (ADCC), trogocystosis, and gp120-specifc IgG subclasses. RESULTS: Additional boosting increased the magnitude of all Fc-mediated effector functions 2 weeks following the additional boost compared with 2 weeks after completing the RV144 regimen. However, only trogocytosis remained higher 24-26 weeks after the last vaccination for the study participants receiving an additional boost compared with those that did not receive an additional boost. The additional boost increased IgG1 and IgG4 but decreased IgG3 gp-120 specific antibodies compared with 2 weeks after completing the RV144 regimen. CONCLUSION: Additional boosting of RV144 improved the magnitude but not the durability of some Fc-mediated effector functions that were associated with vaccine efficacy, with trogocytosis being the most durable.

The Rate of Medial Ulnar Collateral Ligament Repair Is Increasing While Reconstruction Remains the Most Common Procedure Overall Among Early-Career Orthopaedic Surgeons.

Purpose: To determine the practice patterns and complication rates in medial ulnar collateral ligament (MUCL) repair versus reconstruction procedures performed by early-career orthopaedic surgeons each year between 2010 and 2020, stratified by fellowship training and concomitant procedures performed, during their 6-month American Board of Orthopaedic Surgery (ABOS) Case List collection period. Methods: The ABOS database was queried for MUCL reconstruction and MUCL repair procedures reported by ABOS Part II Oral Examination examinees from 2010 to 2020. Surgeon fellowship training background, patient demographics, procedural diagnosis codes, complications, and concomitant procedures were recorded for each case. Differences between overall procedure rates and the associated complications reported were examined. Data regarding the specific injury pathology and other patient-specific characteristics for each case were not available. Results: In total, 187 primary procedures performed to address isolated MUCL injuries were reported. Of those, 83% (n = 155) were reconstructions and 17% (n = 32) were repairs. The annual percentage of MUCL repair increased from 10% (1/10) in 2010 to 38% (8/21) in 2020 (linear regression; R2 = 0.56, P < .05). The cumulative complication rate for MUCL reconstruction (11.6%) was significantly lower than for MUCL repair (25%) from 2010 to 2020 (P < .05). This remained true among subsets of cases from Orthopaedic Sports Medicine, Shoulder & Elbow, and or Hand Surgery fellowship-trained examinees, although only statistically significant in the Hand Surgery subset. Reported complication rates were not significantly different among cases in which concurrent ulnar nerve neuroplasty and/or transposition or concurrent elbow arthroscopy were performed. Conclusions: Among cases reported by ABOS Part II Oral Examination examinees from 2010 to 2020, there was an increasing rate of MUCL repair whereas MUCL reconstruction remained more common overall. Interestingly, the overall complication rates were significantly lower for MUCL reconstruction than for MUCL repair both in isolation and when concurrent procedures were performed. Level of Evidence: Level III, retrospective cohort study.

ALVAC-HIV and AIDSVAX B/E vaccination induce improved immune responses compared with AIDSVAX B/E vaccination alone.

The RV144 phase III vaccine trial demonstrated that ALVAC-HIV and AIDSVAX B/E administration over 6 months resulted in 31% efficacy in preventing HIV acquisition, while administration of AIDSVAX B/E alone in both VAX003 and VAX004 studies failed to show efficacy. In this study, we aimed to understand the impact of ALVAC-HIV on the development of cellular, humoral, and functional immune responses compared to the administration of AIDSVAX B/E alone. ALVAC-HIV in combination with 3 doses of AIDSVAX B/E significantly increased CD4+ HIV-specific T cell responses, polyfunctionality, and proliferation compared with 3 doses of AIDSVAX B/E alone. Additionally, Env-specific plasmablasts and A244-specific memory B cells were identified with a significantly higher magnitude in the group that received ALVAC-HIV. Subsequently, data revealed increased magnitude of plasma IgG binding to and avidity for HIV Env in participants who received ALVAC-HIV compared with 3 doses of AIDSVAX B/E alone. Lastly, levels of the Fc-mediated effector functions antibody-dependent cellular cytotoxicity, NK cell activation, and trogocytosis were significantly increased in participants who received ALVAC-HIV compared with those receiving AIDSVAX B/E alone. Taken together, these results suggest that ALVAC-HIV plays an essential role in developing cellular and humoral immune responses to protein-boosted regimens relative to protein alone.

Viral vector delivered immunogen focuses HIV-1 antibody specificity and increases durability of the circulating antibody recall response.

The modestly efficacious HIV-1 vaccine regimen (RV144) conferred 31% vaccine efficacy at 3 years following the four-shot immunization series, coupled with rapid waning of putative immune correlates of decreased infection risk. New strategies to increase magnitude and durability of protective immunity are critically needed. The RV305 HIV-1 clinical trial evaluated the immunological impact of a follow-up boost of HIV-1-uninfected RV144 recipients after 6-8 years with RV144 immunogens (ALVAC-HIV alone, AIDSVAX B/E gp120 alone, or ALVAC-HIV + AIDSVAX B/E gp120). Previous reports demonstrated that this regimen elicited higher binding, antibody Fc function, and cellular responses than the primary RV144 regimen. However, the impact of the canarypox viral vector in driving antibody specificity, breadth, durability and function is unknown. We performed a follow-up analysis of humoral responses elicited in RV305 to determine the impact of the different booster immunogens on HIV-1 epitope specificity, antibody subclass, isotype, and Fc effector functions. Importantly, we observed that the ALVAC vaccine component directly contributed to improved breadth, function, and durability of vaccine-elicited antibody responses. Extended boosts in RV305 increased circulating antibody concentration and coverage of heterologous HIV-1 strains by V1V2-specific antibodies above estimated protective levels observed in RV144. Antibody Fc effector functions, specifically antibody-dependent cellular cytotoxicity and phagocytosis, were boosted to higher levels than was achieved in RV144. V1V2 Env IgG3, a correlate of lower HIV-1 risk, was not increased; plasma Env IgA (specifically IgA1), a correlate of increased HIV-1 risk, was elevated. The quality of the circulating polyclonal antibody response changed with each booster immunization. Remarkably, the ALVAC-HIV booster immunogen induced antibody responses post-second boost, indicating that the viral vector immunogen can be utilized to selectively enhance immune correlates of decreased HIV-1 risk. These results reveal a complex dynamic of HIV-1 immunity post-vaccination that may require careful balancing to achieve protective immunity in the vaccinated population. Trial registration: RV305 clinical trial (ClinicalTrials.gov number, NCT01435135). ClinicalTrials.gov Identifier: NCT00223080.