Head Kinematics in Youth Ice Hockey by Player Speed and Impact Direction.

Hockey is a fast-paced sport known for body checking, or intentional collisions used to separate opponents from the puck. Exposure to these impacts is concerning, as evidence suggests head impact exposure (HIE), even if noninjurious, can cause long-term brain changes. Currently, there is limited understanding of the effect of impact direction and collision speed on HIE. Video analysis was used to determine speed and direction for 162 collisions from 13 youth athletes. These data were paired with head kinematic data collected with an instrumented mouthpiece. Relationships between peak resultant head kinematics and speeds were evaluated with linear regression. Mean athlete speeds and relative velocity between athletes ranged from 2.05 to 2.76 m/s. Mean peak resultant linear acceleration, rotational velocity, and rotational acceleration were 13.1 g, 10.5 rad/s, and 1112 rad/s2, respectively. Significant relationships between speeds and head kinematics emerged when stratified by contact characteristics. HIE also varied by direction of collision; most collisions occurred in the forward-oblique (ie, offset from center) direction; frontal collisions had the greatest magnitude peak kinematics. These findings indicate that HIE in youth hockey is influenced by speed and direction of impact. This study may inform future strategies to reduce the severity of HIE in hockey.

SARS-COV-2 vaccine responses in renal patient populations.

BACKGROUND: Dialysis patients and immunosuppressed renal patients are at increased risk of COVID-19 and were excluded from vaccine trials. We conducted a prospective multicentre study to assess SARS-CoV-2 vaccine antibody responses in dialysis patients and renal transplant recipients, and patients receiving immunosuppression for autoimmune disease. METHODS: Patients were recruited from three UK centres (ethics:20/EM/0180) and compared to healthy controls (ethics:17/EE/0025). SARS-CoV-2 IgG antibodies to spike protein were measured using a multiplex Luminex assay, after first and second doses of Pfizer BioNTech BNT162b2(Pfizer) or Oxford-AstraZeneca ChAdOx1nCoV-19(AZ) vaccine. RESULTS: Six hundred ninety-two patients were included (260 dialysis, 209 transplant, 223 autoimmune disease (prior rituximab 128(57%)) and 144 healthy controls. 299(43%) patients received Pfizer vaccine and 379(55%) received AZ. Following two vaccine doses, positive responses occurred in 96% dialysis, 52% transplant, 70% autoimmune patients and 100% of healthy controls. In dialysis patients, higher antibody responses were observed with the Pfizer vaccination. Predictors of poor antibody response were triple immunosuppression (adjusted odds ratio [aOR]0.016;95%CI0.002-0.13;p < 0.001) and mycophenolate mofetil (MMF) (aOR0.2;95%CI 0.1-0.42;p < 0.001) in transplant patients; rituximab within 12 months in autoimmune patients (aOR0.29;95%CI 0.008-0.096;p < 0.001) and patients receiving immunosuppression with eGFR 15-29 ml/min (aOR0.031;95%CI 0.11-0.84;p = 0.021). Lower antibody responses were associated with a higher chance of a breakthrough infection. CONCLUSIONS: Amongst dialysis, kidney transplant and autoimmune populations SARS-CoV-2 vaccine antibody responses are reduced compared to healthy controls. A reduced response to vaccination was associated with rituximab, MMF, triple immunosuppression CKD stage 4. Vaccine responses increased after the second dose, suggesting low-responder groups should be prioritised for repeated vaccination. Greater antibody responses were observed with the mRNA Pfizer vaccine compared to adenovirus AZ vaccine in dialysis patients suggesting that Pfizer SARS-CoV-2 vaccine should be the preferred vaccine choice in this sub-group.

Characterization of Head Impact Exposure in Women's Collegiate Soccer.

Soccer players are regularly exposed to head impacts by intentionally heading the ball. Evidence suggests repetitive subconcussive head impacts may affect the brain, and females may be more vulnerable to brain injury than males. This study aimed to characterize head impact exposure among National Collegiate Athletic Association women's soccer players using a previously validated mouthpiece-based sensor. Sixteen players were instrumented during 72 practices and 24 games. Head impact rate and rate of risk-weighted cumulative exposure were compared across session type and player position. Head kinematics were compared across session type, impact type, player position, impact location, and ball delivery method. Players experienced a mean (95% confidence interval) head impact rate of 0.468 (0.289 to 0.647) head impacts per hour, and exposure rates varied by session type and player position. Headers accounted for 89% of head impacts and were associated with higher linear accelerations and rotational accelerations than nonheader impacts. Headers in which the ball was delivered by a long kick had greater peak kinematics (all P < .001) than headers in which the ball was delivered by any other method. Results provide increased understanding of head impact frequency and magnitude in women's collegiate soccer and may help inform efforts to prevent brain injury.

Head and neck cutaneous metastasis of testicular choriocarcinoma.

Testicular choriocarcinoma (CC) is a malignant germ cell tumour which most frequently presents with disseminated metastasis, often involving the lungs, brain and liver. Metastatic are characterised by extensive vascularity, often causing patients to present emergently with potentially life-threatening haemorrhagic complications. We report a patient with disseminated testicular CC, presenting with haemorrhage from a dermal metastatic focus involving the lower lip and mentum, requiring surgical intervention. This unique case illustrates the potential utility of palliative surgery, for the management of symptomatic metastatic disease, such as those caused by testicular CC.

Inhalant allergen sensitization is an independent risk factor for the development of angioedema.

BACKGROUND/OBJECTIVE: The etiology and risk factors for angioedema remain poorly understood with causative triggers often going undiagnosed despite repeated reactions. The purpose of this study was to determine the relationship between inhalant allergen sensitization and angioedema. METHODS: A retrospective review of patients who had in vitro inhalant allergy testing from 2006 to 2010 was performed. Patients with a diagnosis of angioedema who underwent inhalant allergy testing were identified. Analyses for co-morbidities, class of sensitization, seasonal timing of angioedema, and concurrent use of known hypertensive medications that can cause angioedema were performed. RESULTS: There were 1000 patients who underwent inhalant allergy testing and qualified for the study. 37/1000 had at least one episode of angioedema and of these patients, 34 had positive inhalant sensitization testing results. Multivariate regression models showed overall sensitization status, seasonal allergen and epidermal/mite sensitization as independent risk factors (p<0.001, p=0.005, p=0.025 respectively) when controlling for ACE inhibitor use and other covariates. Tree, and epidermal/mite sensitizations were independent risk factors for angioedema in mono-sensitized subject analysis (p=0.028, p=0.029, respectively). CONCLUSION: Both seasonal and perennial allergen sensitizations are independent risk factors for the development of angioedema. In patients with angioedema and an unknown trigger, inhalant allergen sensitization should be considered as a potential contributing factor to the development of angioedema.

Hospital admissions for severe infections in people with chronic kidney disease in relation to renal disease severity and diabetes status.

BACKGROUND: Immunosuppressive agents are being investigated for the treatment of chronic kidney disease (CKD) but may increase risk of infection. This was a retrospective observational study intended to evaluate the risk of hospitalized infection in patients with CKD, by estimated glomerular filtration rate (eGFR) and proteinuria status, aiming to identify the most appropriate disease stage for immunosuppressive intervention. METHODS: Routine UK primary-care and linked secondary-care data were extracted from the Clinical Practice Research Datalink. Patients with a record of CKD were identified and grouped into type 2, type 1 and nondiabetes cohorts. Time-dependent, Cox proportional hazard models were used to determine the likelihood of hospitalized infection. RESULTS: We identified 97 839 patients with a record of CKD, of these 11 719 (12%) had type 2 diabetes. In these latter patients, the adjusted hazard ratios (aHR) were 1.00 (95% CI: 0.80-1.25), 1.00, 1.03 (95% CI: 0.92-1.15), 1.36 (95% CI: 0.20-1.54), 1.82 (95% CI: 1.54-2.15) and 2.41 (95% CI: 1.60-3.63) at eGFR stages G1, G2 (reference), G3a, G3b, G4 and G5, respectively; and 1.00, 1.45 (95% CI: 1.29-1.63) and 1.91 (95% CI: 1.67-2.20) at proteinuria stages A1 (reference), A2 and A3, respectively. All aHRs (except G1 and G3a) were significant, with similar patterns observed within the non-DM and overall cohorts. CONCLUSIONS: eGFR and degree of albuminuria were independent markers of hospitalized infection in both patients with and without diabetes. The same patterns of hazard ratios of eGFR and proteinuria were seen in CKD patients regardless of diabetes status, with the risk of each outcome increasing with a decreasing eGFR and increasing proteinuria. Infection risk increased significantly from eGFR stage G3b and proteinuria stage A2 in type 2 diabetes. Treating type 2 DM patients with CKD at eGFR stages G1-G3a with immunosuppressive therapy may therefore provide a favourable risk-benefit ratio (G1-G3a in type 2 diabetes; G1-G2 in nondiabetes and overall cohorts) although the degree of proteinuria needs to be considered.

Vitamin K antagonists predispose to calciphylaxis in patients with end-stage renal disease.

BACKGROUND/AIMS: Calciphylaxis is associated with a poor prognosis in dialysis patients, and its pathogenesis remains incompletely understood. Although the use of vitamin K antagonists (VKA) has been implicated, previous reports are conflicting. We aimed to determine if vitamin K antagonists conferred an increased risk of calciphylaxis in patients on dialysis. METHODS: We performed a single-centre, retrospective cohort study of 2,234 patients receiving dialysis, and compared the characteristics of those with and without calciphylaxis. RESULTS: We identified 5 cases of calciphylaxis (all female) between January 2009 and December 2013. Overall, 142 patients (6.4%) were treated with VKA during the study period. Calciphylaxis was more common in the VKA group (4 of 142 patients, OR = 61, 95% CI 6.7-546, p = 0.0001). VKA was withdrawn in all cases and treatment instituted with sodium thiosulphate, cinacalcet and supportive measures. All patients recovered, although there was one sudden cerebrovascular death during follow-up. CONCLUSION: Treatment with VKA predisposes to the development of calciphylaxis.

Estimating Disease Prevalence Using Inverse Binomial Pooled Testing.

Monitoring populations of hosts as well as insect vectors is an important part of agricultural and public health risk assessment. In applications where pathogen prevalence is likely low, it is common to test pools of subjects for the presence of infection, rather than to test subjects individually. This technique is known as pooled (group) testing. In this paper, we revisit the problem of estimating the population prevalence p from pooled testing, but we consider applications where inverse binomial sampling is used. Our work is unlike previous research in pooled testing, which has largely assumed a binomial model. Inverse sampling is natural to implement when there is a need to report estimates early on in the data collection process and has been used in individual testing applications when disease incidence is low. We consider point and interval estimation procedures for p in this new pooled testing setting, and we use example data sets from the literature to describe and to illustrate our methods.

Bayesian inference for disease prevalence using negative binomial group testing.

Group testing, also known as pooled testing, and inverse sampling are both widely used methods of data collection when the goal is to estimate a small proportion. Taking a Bayesian approach, we consider the new problem of estimating disease prevalence from group testing when inverse (negative binomial) sampling is used. Using different distributions to incorporate prior knowledge of disease incidence and different loss functions, we derive closed form expressions for posterior distributions and resulting point and credible interval estimators. We then evaluate our new estimators, on Bayesian and classical grounds, and apply our methods to a West Nile Virus data set.

Efficacy and tolerability of sevelamer carbonate in hyperphosphatemic patients who have chronic kidney disease and are not on dialysis.

BACKGROUND AND OBJECTIVES: Sevelamer carbonate is an improved, buffered form of sevelamer hydrochloride developed for the treatment of hyperphosphatemia in patients with chronic kidney disease. This study investigated the ability of sevelamer carbonate to control serum phosphorous in hyperphosphatemic patients who had chronic kidney disease and were not on dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This was an open-label, dosage-titration study. Patients with serum phosphorus > or =5.5 mg/dl were enrolled (n = 46). Sevelamer carbonate was administered for 8 wk. Patients were supplemented with native vitamin D (400 IU). The primary efficacy parameter was the change from baseline in serum phosphorous. Secondary measures included the percentage of serum phosphorus responders; changes in serum lipids, calcium-phosphorus product, and bicarbonate; and safety and tolerability. RESULTS: Sevelamer carbonate treatment resulted in a statistically significant decrease in mean serum phosphorous levels from baseline to end of treatment. A total of 75% of patients with stage 4 and 70% of patients with stage 5 chronic kidney disease achieved the target serum phosphorous at the end of treatment. There were statistically significant decreases in serum calcium-phosphorus product and total and low-density lipoprotein cholesterol at the end of treatment and a statistically significant increase in mean serum bicarbonate levels (from 16.6 to 18.2 mEq/L). Sevelamer carbonate was well tolerated. CONCLUSIONS: Sevelamer carbonate is an effective and well-tolerated therapy for the control of phosphorous levels in hyperphosphatemic patients who have chronic kidney disease and are not on dialysis.

A randomized controlled trial of late conversion from CNI-based to sirolimus-based immunosuppression following renal transplantation.

Maintenance immunosuppression with calcineurin inhibitors (CNIs) following renal transplantation is associated with nephrotoxicity and accelerated graft loss. We aimed to assess whether conversion to sirolimus-based immunosuppression would affect the progression of renal impairment. In this single center, randomized controlled trial, 40 renal transplant recipients between 6 months and 8 years post-transplant were randomly assigned to remain on their CNI (cyclosporin or tacrolimus) or to switch to sirolimus. The primary outcome measure was change in glomerular filtration rate (GFR) measurement at 12 months. Analysis was by intention-to-treat. Of the 40 patients randomized, 2 patients never took the study drugs and were excluded, leaving 19 patients per group. There was a significant change in GFR at 12 months following conversion to sirolimus (12.9 mL/min, 95% CI 6.1-19.7; p < 0.001). Following conversion, the principal adverse events were the development of rashes (68%), particularly acne, and mouth ulcers (32%). No patient in either group experienced an acute rejection episode. In renal transplant recipients, a change in maintenance therapy from CNIs to sirolimus is associated with significant improvement in GFR at 12 months.

Expression of silencer of death domains and death-receptor-3 in normal human kidney and in rejecting renal transplants.

We have previously reported the pattern of cellular expression of tumor necrosis factor receptors (TNFR) in human kidney and their altered expression in transplant rejection. We have extended our studies to examine the expression of Silencer of Death Domains (SODD), a protein that binds to the cytoplasmic portion of TNFR1 to inhibit signaling in the absence of ligand. In normal human kidney SODD is expressed in glomerular endothelial cells where it colocalizes with TNFR1. During acute rejection both SODD and TNFR1 are lost from glomeruli, but we found strong expression of SODD on the luminal surface of tubular epithelial cells. This occurs in the absence of detectable TNFR1 expression, suggesting that SODD could interact with other proteins at these sites. Several other members of the TNF superfamily, including Fas and death receptors (DR)-3, -4, and -5, also contain intracellular death domains, but SODD only interacts with the death domain of DR3. We therefore studied the expression of DR3 in human kidney, and report that this death receptor is up-regulated in renal tubular epithelial cells and endothelial cells of some interlobular arteries, in parallel with SODD, during acute transplant rejection. In less severe rejection episodes, DR3 and SODD were more focally induced, generally at sites of mononuclear cell infiltrates. In ischemic allografts, eg, with acute tubular necrosis but no cellular rejection, DR3 was induced on tubular epithelial cells and on glomerular endothelial cells. These data confirm that TNF receptor family members are expressed in a regulated manner during renal transplant rejection, and identify DR3 as a potential inducible mediator of tubular inflammation and injury.

Interleukin 4 reduces expression of inhibitory receptors on B cells and abolishes CD22 and Fc gamma RII-mediated B cell suppression.

Inhibitory receptors CD22, Fc gamma RII (CD32), CD72, and paired immunoglobulin-like receptor (PIR)-B are critically involved in negatively regulating the B cell immune response and in preventing autoimmunity. Here we show that interleukin 4 (IL-4) reduces expression of all four on activated B cells at the level of messenger RNA and protein. This reduced expression is dependent on continuous exposure to IL-4 and is mediated through Stat6. Coligation of Fc gamma RII to the B cell receptor (BCR) via intact IgG increases the B cell activation threshold and suppresses antigen presentation. IL-4 completely abolishes these negative regulatory effects of Fc gamma RII. CD22 coligation with the BCR also suppresses activation -- this suppression too is abolished by IL-4. Thus, IL-4 is likely to enhance the B cell immune response by releasing B cells from inhibitory receptor suppression. By this coordinate reduction in expression of inhibitory receptors, and release from CD22 and Fc gamma RII-mediated inhibition, IL-4 is likely to play a role in T cell help of B cells and the development of T helper cell type 2 responses. Conversely, B cell activation in the absence of IL-4 would be more difficult to achieve, contributing to the maintenance of B cell tolerance in the absence of T cell help.