The National Football League Concussion Protocol: A Review.

Sport-related concussion remains an area of high concern for contact sport athletes and their families, as well as for the medical and scientific communities. The National Football League (NFL), along with the NFL Players Association and experts in the field, has developed protocols for the detection and management of sport-related concussions. This article reviews the NFL's most recent concussion protocol including preseason education and baseline testing for players, concussion surveillance by gameday medical teams and neurotrauma consultants and athletic trainers, gameday concussion protocol and procedures, and return to participation guidelines.

Methotrexate hampers immunogenicity to BNT162b2 mRNA COVID-19 vaccine in immune-mediated inflammatory disease.

OBJECTIVE: To investigate the humoral and cellular immune response to messenger RNA (mRNA) COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment. METHODS: Established patients at New York University Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunisation. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analysed for humoral response. Cellular immune response to SARS-CoV-2 was further analysed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany, were also analysed for humoral immune response. RESULTS: Although healthy subjects (n=208) and patients with IMID on biologic treatments (mostly on tumour necrosis factor blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, patients with IMID on methotrexate do not demonstrate an increase in CD8+ T-cell activation after vaccination. CONCLUSIONS: In two independent cohorts of patients with IMID, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut-offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunisation efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines.

Prevalence of Inflammatory Heart Disease Among Professional Athletes With Prior COVID-19 Infection Who Received Systematic Return-to-Play Cardiac Screening.

Importance: The major North American professional sports leagues were among the first to return to full-scale sport activity during the coronavirus disease 2019 (COVID-19) pandemic. Given the unknown incidence of adverse cardiac sequelae after COVID-19 infection in athletes, these leagues implemented a conservative return-to-play (RTP) cardiac testing program aligned with American College of Cardiology recommendations for all athletes testing positive for COVID-19. Objective: To assess the prevalence of detectable inflammatory heart disease in professional athletes with prior COVID-19 infection, using current RTP screening recommendations. Design, Setting, and Participants: This cross-sectional study reviewed RTP cardiac testing performed between May and October 2020 on professional athletes who had tested positive for COVID-19. The professional sports leagues (Major League Soccer, Major League Baseball, National Hockey League, National Football League, and the men's and women's National Basketball Association) implemented mandatory cardiac screening requirements for all players who had tested positive for COVID-19 prior to resumption of team-organized sports activities. Exposures: Troponin testing, electrocardiography (ECG), and resting echocardiography were performed after a positive COVID-19 test result. Interleague, deidentified cardiac data were pooled for collective analysis. Those with abnormal screening test results were referred for additional testing, including cardiac magnetic resonance imaging and/or stress echocardiography. Main Outcomes and Measures: The prevalence of abnormal RTP test results potentially representing COVID-19-associated cardiac injury, and results and outcomes of additional testing generated by the initial screening process. Results: The study included 789 professional athletes (mean [SD] age, 25 [3] years; 777 men [98.5%]). A total of 460 athletes (58.3%) had prior symptomatic COVID-19 illness, and 329 (41.7%) were asymptomatic or paucisymptomatic (minimally symptomatic). Testing was performed a mean (SD) of 19 (17) days (range, 3-156 days) after a positive test result. Abnormal screening results were identified in 30 athletes (3.8%; troponin, 6 athletes [0.8%]; ECG, 10 athletes [1.3%]; echocardiography, 20 athletes [2.5%]), necessitating additional testing; 5 athletes (0.6%) ultimately had cardiac magnetic resonance imaging findings suggesting inflammatory heart disease (myocarditis, 3; pericarditis, 2) that resulted in restriction from play. No adverse cardiac events occurred in athletes who underwent cardiac screening and resumed professional sport participation. Conclusions and Relevance: This study provides large-scale data assessing the prevalence of relevant COVID-19-associated cardiac pathology with implementation of current RTP screening recommendations. While long-term follow-up is ongoing, few cases of inflammatory heart disease have been detected, and a safe return to professional sports activity has thus far been achieved.

Interleukin-17 Inhibition in Spondyloarthritis Is Associated With Subclinical Gut Microbiome Perturbations and a Distinctive Interleukin-25-Driven Intestinal Inflammation.

OBJECTIVE: To characterize the ecological effects of biologic therapies on the gut bacterial and fungal microbiome in psoriatic arthritis (PsA)/spondyloarthritis (SpA) patients. METHODS: Fecal samples from PsA/SpA patients pre- and posttreatment with tumor necrosis factor inhibitors (TNFi; n = 15) or an anti-interleukin-17A monoclonal antibody inhibitor (IL-17i; n = 14) underwent sequencing (16S ribosomal RNA, internal transcribed spacer and shotgun metagenomics) and computational microbiome analysis. Fecal levels of fatty acid metabolites and cytokines/proteins implicated in PsA/SpA pathogenesis or intestinal inflammation were correlated with sequence data. Additionally, ileal biopsies obtained from SpA patients who developed clinically overt Crohn's disease (CD) after treatment with IL-17i (n = 5) were analyzed for expression of IL-23/Th17-related cytokines, IL-25/IL-17E-producing cells, and type 2 innate lymphoid cells (ILC2s). RESULTS: There were significant shifts in abundance of specific taxa after treatment with IL-17i compared to TNFi, particularly Clostridiales (P = 0.016) and Candida albicans (P = 0.041). These subclinical alterations correlated with changes in bacterial community co-occurrence, metabolic pathways, IL-23/Th17-related cytokines, and various fatty acids. Ileal biopsies showed that clinically overt CD was associated with expansion of IL-25/IL-17E-producing tuft cells and ILC2s (P < 0.05), compared to pre-IL-17i treatment levels. CONCLUSION: In a subgroup of SpA patients, the initiation of IL-17A blockade correlated with features of subclinical gut inflammation and intestinal dysbiosis of certain bacterial and fungal taxa, most notably C albicans. Further, IL-17i-related CD was associated with overexpression of IL-25/IL-17E-producing tuft cells and ILC2s. These results may help to explain the potential link between inhibition of a specific IL-17 pathway and the (sub)clinical gut inflammation observed in SpA.

Sport-Related Structural Brain Injury: 3 Cases of Subdural Hemorrhage in American High School Football.

BACKGROUND: The risk of sport-related concussion (SRC) has emerged as a major public health concern. In rare instances, sport-related head injuries can be even more severe, such as subdural hemorrhage, epidural hemorrhage, or malignant cerebral edema. Unlike SRCs, sport-related structural brain injury (SRSBI) is rare, may require neurosurgical intervention, and can lead to permanent neurologic deficit or death. Data characterizing SRSBI are limited, and many have recognized the need to better understand these catastrophic brain injuries. The goal of the current series is to describe, in detail, the presentation, management, and outcomes of examples of these rare injuries. CASE DESCRIPTION: During the fall of 2015, three high school football players presented with acute subdural hemorrhages following in-game collisions and were treated at our institution within a span of 2 months. For the 2 athletes who required surgical intervention, a previous SRC was sustained within 4 weeks before the catastrophic event. One year after injury, 2 players have returned to school, though with persistent deficits. One patient remains nonverbal and wheelchair bound. None of the athletes has returned to sports. CONCLUSIONS: Acute subdural hemorrhage resultant from an in-game football collision is rare. The temporal proximity of the reported SRSBIs to recent SRCs emphasizes the importance of return-to-play protocols and raises questions regarding the possibility of second impact syndrome. Although epidemiologic conclusions cannot be drawn from this small sample, these cases provide a unique opportunity to demonstrate the presentation, management, and long-term outcomes of SRSBI in American high school football.

Sport-related structural brain injury associated with arachnoid cysts: a systematic review and quantitative analysis.

OBJECTIVE Arachnoid cysts (ACs) are congenital lesions bordered by an arachnoid membrane. Researchers have postulated that individuals with an AC demonstrate a higher rate of structural brain injury after trauma. Given the potential neurological consequences of a structural brain injury requiring neurosurgical intervention, the authors sought to perform a systematic review of sport-related structural-brain injury associated with ACs with a corresponding quantitative analysis. METHODS Titles and abstracts were searched systematically across the following databases: PubMed, Embase, CINAHL, and PsycINFO. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Peer-reviewed case reports, case series, or observational studies that reported a structural brain injury due to a sport or recreational activity (hereafter referred to as sport-related) with an associated AC were included. Patients were excluded if they did not have an AC, suffered a concussion without structural brain injury, or sustained the injury during a non-sport-related activity (e.g., fall, motor vehicle collision). Descriptive statistical analysis and time to presentation data were summarized. Univariate logistic regression models to assess predictors of neurological deficit, open craniotomy, and cystoperitoneal shunt were completed. RESULTS After an initial search of 994 original articles, 52 studies were found that reported 65 cases of sport-related structural brain injury associated with an AC. The median age at presentation was 16 years (range 4-75 years). Headache was the most common presenting symptom (98%), followed by nausea and vomiting in 49%. Thirteen patients (21%) presented with a neurological deficit, most commonly hemiparesis. Open craniotomy was the most common form of treatment (49%). Bur holes and cyst fenestration were performed in 29 (45%) and 31 (48%) patients, respectively. Seven patients (11%) received a cystoperitoneal shunt. Four cases reported medical management only without any surgical intervention. No significant predictors were found for neurological deficit or open craniotomy. In the univariate model predicting the need for a cystoperitoneal shunt, the odds of receiving a shunt decreased as age increased (p = 0.004, OR 0.62 [95% CI 0.45-0.86]) and with male sex (p = 0.036, OR 0.15 [95% CI 0.03-0.88]). CONCLUSIONS This systematic review yielded 65 cases of sport-related structural brain injury associated with ACs. The majority of patients presented with chronic symptoms, and recovery was reported generally to be good. Although the review is subject to publication bias, the authors do not find at present that there is contraindication for patients with an AC to participate in sports, although parents and children should be counseled appropriately. Further studies are necessary to better evaluate AC characteristics that could pose a higher risk of adverse events after trauma.

A Delphi Consensus Approach to Challenging Case Scenarios in Moderate-to-Severe Psoriasis: Part 1.

INTRODUCTION: Traditional clinical trials in psoriasis exclude a significant proportion of patients with complex disease and comorbidities. A consensus panel of 14 experts in the field of psoriasis was formed to conduct a Delphi method exercise to identify difficult-to-treat psoriasis clinical scenarios and to rank treatment approaches. METHODS: The exercise consisted of both survey questionnaires and a live meeting to review and discuss current data (as of 2009, when the exercise was conducted) and arrive at a consensus for optimal treatment options. Seventy difficult treatment scenarios were identified, and the top 24 were selected for discussion at the live meeting. RESULTS: Six of the 24 discussed case scenarios are presented in this article (another five are presented in Part 2): (1) psoriasis with human papilloma virus-induced cervical or anogenital dysplasia; (2) concomitant psoriasis and systemic lupus erythematosus; (3) severe psoriatic nail disease causing functional or emotional impairment; (4) psoriasis therapies that potentially reduce cardiovascular morbidity and mortality; (5) older patients (≥65 years of age) with psoriasis; and (6) severe scalp psoriasis that is unresponsive to topical therapy. CONCLUSION: The Delphi exercise resulted in guidelines for practicing physicians to utilize when confronted with challenging patients with psoriasis.

Disseminated superficial porokeratosis.

A 62-year-old woman with psoriasis and psoriatic arthritis presented for evaluation and treatment of a one-week history of pruritic, pink spots on her trunk and extremities. Several weeks prior, therapy with certolizumab pegol and methotrexate was started for her psoriatic arthritis. A biopsy specimen was consistent with the diagnosis of porokeratosis. Owing to the setting of immunosuppression and presence of symmetric pruritic lesions on non-sun exposed areas, the diagnosis of disseminated superficial porokeratosis was made.

Syphilis mimicking Reiter's syndrome in an HIV-positive patient.

A 38-year-old man with HIV infection presented with panuveitis, urethritis, and a papulosquamous eruption on his palms and soles. Careful physical and laboratory examination led to the diagnosis of syphilitic keratoderma, uveitis, and balanitis. The patient was successfully treated with penicillin and prednisone therapy. Because the initial presentation was difficult to distinguish from the symptoms of Reiter's syndrome, a high degree of clinical suspicion was required to accurately diagnose syphilis, a curable and potentially fatal disease.