Immunogenicity of quadrivalent meningococcal conjugate vaccine in frequent platelet donors.

Frequent plateletpheresis is associated with severe lymphopenia of uncertain clinical significance. We assessed the functional impact of frequent platelet donations and associated lymphopenia on the response to neoantigens. We conducted a prospective study of 102 platelet donors (HIV uninfected) who were naive to meningococcal vaccination recruited at Brigham and Women's Hospital. One dose of quadrivalent meningococcal conjugate vaccine was administered. Seroresponse was defined as a fourfold increase of serum bactericidal antibody titers and seroprotection was defined as postvaccination titers of ≥1:8, for each of the 4 vaccine antigens (A, C, W, and Y). Mean age of participants was 61 years, 69% were male, and medial number of platelet donations in prior year was 14 (interquartile range, 4-20). Frequent platelet donors had a low CD4 count (14% with ≤200/µL and 34% with ≤350/µL). Seroresponse rates varied from 68% for serogroup Y to 86% for serogroup A and were higher for participants with baseline titers of <1:8. Postvaccination seroprotection rates varied from 76% for serogroup Y to 96% for serogroup A. After adjustments for age, sex, and frequent donations, lower total lymphocyte or lower CD4 counts were not associated with lower responses. These data suggest no impairment by plateletpheresis-associated lymphopenia on response to these neoantigens. This trial was registered at www.clinicaltrials.gov as #NCT04224311.

Rotator Cuff Injuries in the Pediatric Population: A Retrospective Review of Patient Characteristics and Treatment at a Single Center.

BACKGROUND: As youth participation in contact and overhead sports has increased in recent decades, so has the occurrence of injuries of the shoulder. Rotator cuff injury (RCI) is an infrequent shoulder pathology in pediatric patients and its description in the literature has been scarce. A greater understanding of RCI characteristics and treatment outcomes in children and adolescents would improve our understanding of this pathology and help to better guide clinical decision-making. HYPOTHESIS: To identify pediatric patients with magnetic resonance imaging-confirmed RCI treated at a single center to summarize injury characteristics, treatment, and outcomes. It was hypothesized that injuries would occur predominantly in overhead throwing athletes and would demonstrate good outcomes among both operatively and nonoperatively treated patients. STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 4. METHODS: A retrospective review of pediatric patients (<18 years old) diagnosed with and treated for an RCI between January 1, 2011 and January 31, 2021. Patient demographics, injury mechanism and type, treatment, and outcomes were collected. Descriptive statistics were performed. Bivariate testing was used to compare operatively and nonoperatively treated cohorts. RESULTS: A total of 52 pediatric patients treated for a rotator cuff avulsion, partial tear, or complete tear were identified. Mean age was 15 years and 67% of patients were male. Injuries were related most commonly to participation in throwing sports. Operative management occurred in 23% of patients, while 77% were managed nonoperatively. Treatment cohorts differed based on tear type, with all complete tears being managed operatively (P < 0.01). Associated shoulder pathology was common, with the most frequent finding being anterior shoulder instability pathology. Return to play was longer for operatively managed patients (7.1 vs 4.5 months; P < 0.01). CONCLUSION: The present study expands the limited data available regarding RCIs in pediatric patients. Most injuries are associated with sports and involve the supraspinatus tendon. RCIs were associated with good outcomes and low rates of reinjury in patients managed both nonoperative and operatively. RCI should be considered in throwing athletes with shoulder pain, even in skeletally immature patients. CLINICAL RELEVANCE: This retrospective study fills the hole in the literature by detailing the patterns associated with RCI characteristics and treatment outcomes. In contrast to studies of adult RCIs, our results suggest that outcomes are good regardless of treatment type.

Vestibular Schwannoma and Tinnitus: A Systematic Review of Microsurgery Compared to Gamma Knife Radiosurgery.

Background: Vestibular schwannoma (VS) is a benign tumor of the eighth cranial nerve formed from neoplastic Schwann cells. Although VS can cause a variety of symptoms, tinnitus is one of the most distressing symptoms for patients and can greatly impact quality of life. The objective of this systematic review is to comprehensively examine and compare the outcomes related to tinnitus in patients undergoing treatment for VS. Specifically, it evaluates patient experiences with tinnitus following the removal of VS using the various surgical approaches of traditional surgical resection and gamma knife radiosurgery (GKS). By delving into various aspects such as the severity of tinnitus post-treatment, the duration of symptom relief, patient quality of life, new onset of tinnitus after VS treatment, and any potential complications or side effects, this review aims to provide a detailed analysis of VS treatment on tinnitus outcomes. Methods: Following PRISMA guidelines, articles were included from PubMed, Science Direct, Scopus, and EMBASE. Quality assessment and risk of bias analysis were performed using a ROBINS-I tool. Results: Although VS-associated tinnitus is variable in its intensity and persistence post-resection, there was a trend towards a decreased tinnitus burden in patients. Irrespective of the surgical approach or the treatment with GKS, there were cases of persistent or worsened tinnitus within the studied cohorts. Conclusion: The findings of this systematic review highlight the complex relationship between VS resection and tinnitus outcomes. These findings underscore the need for individualized patient counseling and tailored treatment approaches in managing VS-associated tinnitus. The findings of this systematic review may help in guiding clinicians towards making more informed and personalized healthcare decisions. Further studies must be completed to fill gaps in the current literature.

The effect of surface compliance on overground running biomechanics. A systematic review and meta-analysis.

The surface upon which running is performed has been suggested as a potential cause of many running-related injuries. It remains unclear, however, what effect surface compliance has on running biomechanics. This study aimed to investigate the effect of surface compliance on overground running biomechanics through a systematic review and meta-analysis. Using the PRISMA Protocols Statement, a search was conducted in three electronic databases (CINAHL, EMBASE, EBSCO) using the following anchoring terms: running, overground surface, biomechanics, kinematics, tibial acceleration, pressure and force. Following de-duplication, title/abstract screening and full-text review, 25 articles (n = 492) were identified which met all inclusion criteria, 22 (n = 392) of which were subsequently included in quantitative synthesis. Random effects analysis found that peak tibial acceleration was significantly lower when running on softer surfaces (P = 0.01, Z = 2.51; SMD = -0.8; 95% CI =-1.42 to -0.18). However, peak vertical ground reaction force, loading rate and ground contact time were not significantly different when comparing hard and soft surfaces. Since peak tibial acceleration has been associated with an increased risk of tibial stress injuries, the results of this meta-analysis suggest that running on softer surfaces to reduce impact stress on the tibia is probably justified to lower the risk of running-related stress injuries.

Quantifying the impact of the coronavirus 2019 pandemic on youth sports-related injuries in the USA.

The purpose of this study was to estimate monthly and annual trends in youth sports-related injury over the years 2016-2020 using the National Electronic Injury Surveillance System (NEISS) database to measure the impact of COVID-19 on overall and sport-specific rates of injury. Children and adolescents (0-19 years) presenting to USA emergency departments with sport participation injury from 2016 to 2020 were identified. Descriptive statistical analyses were performed of injury patterns. An interrupted time series analysis was applied to estimate changes in injury trends during COVID-19. Proportional changes in injury characteristics during this period were examined. An estimated 5 078 490 sports-related injuries were identified with an annual incidence of 1406 injuries per 100 000 population. Seasonal peaks in injuries occurred during September and May. About 58% of injuries were associated with contact sports, such as basketball, football, and soccer, and the most common injuries were sprains and strains. After the pandemic onset, there was a statistically significant 59% decrease in national youth sports-related injuries compared with the average estimates for 2016-2019. While the distribution of injury characteristics did not appear to change, the location of injury appeared to shift away from school toward alternative settings. A significant reduction in youth sports-related injuries was identified in 2020 coinciding with the COVID-19 pandemic, persisting throughout the rest of the year. No changes in the anatomic or demographic distribution of injuries were identified. This study expands our epidemiologic understanding of youth sports-related injury trends and how they changed following the pandemic onset.

Relationship Between Myocardial Injury During Index Hospitalization for SARS-CoV-2 Infection and Longer-Term Outcomes.

Background Myocardial injury in patients with COVID-19 is associated with increased mortality during index hospitalization; however, the relationship to long-term sequelae of SARS-CoV-2 is unknown. This study assessed the relationship between myocardial injury (high-sensitivity cardiac troponin T level) during index hospitalization for COVID-19 and longer-term outcomes. Methods and Results This is a prospective cohort of patients who were hospitalized at a single center between March and May 2020 with SARS-CoV-2. Cardiac biomarkers were systematically collected. Outcomes were adjudicated and stratified on the basis of myocardial injury. The study cohort includes 483 patients who had high-sensitivity cardiac troponin T data during their index hospitalization. During index hospitalization, 91 (18.8%) died, 70 (14.4%) had thrombotic complications, and 126 (25.6%) had cardiovascular complications. By 12 months, 107 (22.2%) died. During index hospitalization, 301 (62.3%) had cardiac injury (high-sensitivity cardiac troponin T≧14 ng/L); these patients had 28.6%, 32.2%, and 33.2% mortality during index hospitalization, at 6 months, and at 12 months, respectively, compared with 4.1%, 4.9%, and 4.9% mortality for those with low-level positive troponin and 0%, 0%, and 0% for those with undetectable troponin. Of 392 (81.2%) patients who survived the index hospitalization, 94 (24%) had at least 1 readmission within 12 months, of whom 61 (65%) had myocardial injury during the index hospitalization. Of 377 (96%) patients who were alive and had follow-up after the index hospitalization, 211 (56%) patients had a documented, detailed clinical assessment at 6 months. A total of 78 of 211 (37.0%) had ongoing COVID-19-related symptoms; 34 of 211 (16.1%) had neurocognitive decline, 8 of 211 (3.8%) had increased supplemental oxygen requirements, and 42 of 211 (19.9%) had worsening functional status. Conclusions Myocardial injury during index hospitalization for COVID-19 was associated with increased mortality and may predict who are more likely to have postacute sequelae of COVID-19. Among patients who survived their index hospitalization, the incremental mortality through 12 months was low, even among troponin-positive patients.

Evaluation of Three Commercial and Two Non-Commercial Immunoassays for the Detection of Prior Infection to SARS-CoV-2.

BACKGROUND: Serological testing provides a record of prior infection with SARS-CoV-2, but assay performance requires independent assessment. METHODS: We evaluated 3 commercial (Roche Diagnostics pan-IG, and Epitope Diagnostics IgM and IgG) and 2 non-commercial (Simoa and Ragon/MGH IgG) immunoassays against 1083 unique samples that included 251 PCR-positive and 832 prepandemic samples. RESULTS: The Roche assay registered the highest specificity 99.6% (3/832 false positives), the Ragon/MGH assay 99.5% (4/832), the primary Simoa assay model 99.0% (8/832), and the Epitope IgG and IgM 99.0% (8/830) and 99.5% (4/830), respectively. Overall sensitivities for the Simoa, Roche pan-IG, Epitope IgG, Ragon/MGH IgG, and Epitope IgM were 92.0%, 82.9%, 82.5%, 64.5% and 47.0%, respectively. The Simoa immunoassay demonstrated the highest sensitivity among samples stratified by days postsymptom onset (PSO), <8 days PSO (57.69%) 8-14 days PSO (93.51%), 15-21 days PSO (100%), and > 21 days PSO (95.18%). CONCLUSIONS: All assays demonstrated high to very high specificities while sensitivities were variable across assays.

Poststudy Point-of-Care Oral Fluid Testing in Human Immunodeficiency Virus-1 Vaccinees.

BACKGROUND: Experimental human immunodeficiency virus (HIV)-1 vaccines frequently elicit antibodies against HIV-1 that may react with commonly used HIV diagnostic tests, a phenomenon known as vaccine-induced seropositivity/seroreactivity (VISP/VISR). We sought to determine, under clinic conditions, whether a patient-controlled HIV test, OraQuick ADVANCE Rapid HIV-1/2 Antibody Test, detected HIV-1 vaccine-induced antibodies. METHODS: Plasma assessment of HIV-1 cross-reactivity was examined in end-of-study samples from 57 healthy, HIV-uninfected participants who received a candidate vaccine that has entered Phase 2B and 3 testing. We also screened 120 healthy, HIV-uninfected, unblinded HIV-1 vaccine participants with VISP/VISR for an assessment using saliva. These participants came from 21 different parent vaccine protocols representing 17 different vaccine regimens, all of which contained an HIV-1 envelope immunogen. OraQuick ADVANCE was compared with results from concurrent blood samples using a series of commercial HIV screening immunoassays. RESULTS: Fifty-seven unique participant plasma samples were assayed in vitro, and only 1 (1.8%) was reactive by OraQuick ADVANCE. None of the 120 clinic participants (0%; 95% confidence interval, 0% to 3.7%) tested positive by OraQuick ADVANCE, and all were confirmed to be uninfected by HIV-1 viral ribonucleic acid testing. One hundred eighteen of the 120 (98.3%) participants had a reactive HIV test for VISP/VISR: 77 (64%) had at least 1 reactive fourth-generation HIV-1 diagnostic test (P < .0001 vs no reactive OraQuick ADVANCE results), and 41 (34%) only had a reactive test by the less specific third-generation Abbott Prism assay. CONCLUSIONS: These data suggest that this widely available patient-controlled test has limited reactivity to HIV-1 antibodies elicited by these candidate HIV-1 vaccines.

Evaluation of two commercial and two non-commercial immunoassays for the detection of prior infection to SARS-CoV-2.

Background Seroepidemiology is an important tool to characterize the epidemiology and immunobiology of SARS-CoV-2 but many immunoassays have not been externally validated raising questions about reliability of study findings. To ensure meaningful data, particularly in a low seroprevalence population, assays need to be rigorously characterized with high specificity. Methods We evaluated two commercial (Roche Diagnostics and Epitope Diagnostics IgM/IgG) and two non-commercial (Simoa and Ragon/MGH IgG) immunoassays against 68 confirmed positive and 232 pre-pandemic negative controls. Sensitivity was stratified by time from symptom onset. The Simoa multiplex assay applied three pre-defined algorithm models to determine sample result. Results The Roche and Ragon/MGH IgG assays each registered 1/232 false positive, the primary Simoa model registered 2/232 false positives, and the Epitope registered 2/230 and 3/230 false positives for the IgG and IgM assays respectively. Sensitivity >21 days post symptom-onset was 100% for all assays except Epitope IgM, but lower and/or with greater variability between assays for samples collected 9-14 days (67-100%) and 15-21 days (69-100%) post-symptom onset. The Simoa and Epitope IgG assays demonstrated excellent sensitivity earlier in the disease course. The Roche and Ragon/MGH IgG assays were less sensitive during early disease, particularly among immunosuppressed individuals. Conclusions The Epitope IgG demonstrated good sensitivity and specificity. The Roche and Ragon/MGH IgG assays registered rare false positives with lower early sensitivity. The Simoa assay primary model had excellent sensitivity and few false positives.