Contact sport participation and chronic traumatic encephalopathy are associated with altered severity and distribution of cerebral amyloid angiopathy.

Cerebral amyloid angiopathy (CAA) consists of beta-amyloid deposition in the walls of the cerebrovasculature and is commonly associated with Alzheimer's disease (AD). However, the association of CAA with repetitive head impacts (RHI) and with chronic traumatic encephalopathy (CTE) is unknown. We evaluated the relationship between RHI from contact sport participation, CTE, and CAA within a group of deceased contact sport athletes (n = 357), a community-based cohort (n = 209), and an AD cohort from Boston University AD Center (n = 241). Unsupervised hierarchal cluster analysis demonstrated a unique cluster (n = 11) with increased CAA in the leptomeningeal vessels compared to the intracortical vessels (p < 0.001) comprised of participants with significantly greater frequencies of CTE (7/11) and history of RHI. Overall, participants with CTE (n = 251) had more prevalent (p < 0.001) and severe (p = 0.010) CAA within the frontal leptomeningeal vessels compared to intracortical vessels. Compared to those with AD, participants with CTE had more severe CAA in frontal than parietal lobes (p < 0.001) and more severe CAA in leptomeningeal than intracortical vessels (p = 0.002). The overall frequency of CAA in participants with CTE was low, and there was no significant association between contact sport participation and the presence of CAA. However, in those with CAA, a history of contact sports was associated with increased CAA severity in the frontal leptomeningeal vessels (OR = 4.01, 95% CI 2.52-6.38, p < 0.001) adjusting for AD, APOE ε4 status, and age. Participants with CAA had increased levels of sulcal tau pathology and decreased levels of the synaptic marker PSD-95 (p's < 0.05), and CAA was a predictor of dementia (OR = 1.75, 95% CI 1.02-2.99, p = 0.043) adjusting for age, sex, and comorbid pathology. Overall, contact sport participation and CTE were associated with more severe frontal and leptomeningeal CAA, and CAA was independently associated with worse pathological and clinical outcomes.

De-escalation of High-flow Respiratory Support for Children Admitted with Bronchiolitis: A Quality Improvement Initiative.

Bronchiolitis is the most common cause for hospitalization in the first year of life, with hypoxemia and acute respiratory failure as major determinants leading to hospitalization. In addition, the lack of existing guidelines for weaning and discontinuing supplemental oxygen, including high-flow nasal cannula, may contribute to prolonged hospitalization and increased resource utilization. Methods: This single-center quality improvement initiative assessed the effect of implementing a standardized care process for weaning and discontinuing high-flow oxygen for patients hospitalized with bronchiolitis. Patients aged 1-24 months with bronchiolitis admitted to the general wards or ICU step-down unit from February 1, 2018, and January 31, 2020 were included in the study. Primary outcomes included length of stay and time on supplemental oxygen, with time on high-flow oxygen and length of time in ICU step-down unit as secondary outcomes. Balancing measures included transfer rate to Pediatric Intensive Care Unit, intubation rate, 7- and 30-day readmission rates, and 7- and 30-day ED visits after discharge. Results: Following the standardized care process implementation, the mean length of stay decreased from 60.7 hours to 46.7 hours (P < 0.01). In addition, the mean time on any supplemental oxygen decreased by 47% (P < 0.01), the mean time on high-flow oxygen decreased by 45% (P < 0.01), and the mean time in the ICU step-down unit decreased by 27% (P =< 0.01). Balancing measures remained unchanged with no statistically significant differences. Conclusion: Implementing a standardized care process for weaning and discontinuing high-flow oxygen may reduce the length of stay and resource utilization for patients hospitalized with bronchiolitis.

Acute Kidney Injury Among Children Admitted With Viral Rhabdomyolysis.

BACKGROUND: Infectious etiologies cause a large portion of pediatric rhabdomyolysis. Among pediatric patients with rhabdomyolysis, it is unknown who will develop acute kidney injury (AKI). We sought to test the hypothesis that a viral etiology would be associated with less AKI in children admitted with rhabdomyolysis than a nonviral etiology. METHODS: In this single-center retrospective cohort study, patients <21 years of age admitted with acute rhabdomyolysis from May 1, 2010, through December 31, 2018, were studied. The primary outcome was development of AKI, defined by using the Kidney Disease: Improving Global Outcomes guidelines. The primary predictor was identification of viral infection by laboratory testing or clinical diagnosis. Covariates included age, sex, race, insurance provider, presence of proteinuria and myoglobinuria, and initial creatinine kinase and serum urea nitrogen. Routine statistics and multivariable logistic modeling were performed via SAS 9.4 (SAS Institute, Inc, Cary, NC). RESULTS: In total, 319 pediatric patients with rhabdomyolysis were studied. The median age was 13 years. Patients were predominately male (69.9%), non-Hispanic Black (55.2%), and publicly insured (45.1%). We found no difference in the rates of AKI in those with a viral diagnosis versus those without a viral diagnosis (30 of 77 [39.0%] vs 111 of 234 [47.4%]; P = .19). Multivariable analysis revealed that viral diagnosis was not associated with the development of AKI. Patients ≥13 years of age, male patients, and those with proteinuria and elevated serum urea nitrogen on admission had increased odds of developing AKI. CONCLUSIONS: In our study, viral rhabdomyolysis did not have lower rates of AKI compared with nonviral etiologies of AKI; therefore, providers should consider continued caution in these patients.

Variation in TMEM106B in chronic traumatic encephalopathy.

The genetic basis of chronic traumatic encephalopathy (CTE) is poorly understood. Variation in transmembrane protein 106B (TMEM106B) has been associated with enhanced neuroinflammation during aging and with TDP-43-related neurodegenerative disease, and rs3173615, a missense coding SNP in TMEM106B, has been implicated as a functional variant in these processes. Neuroinflammation and TDP-43 pathology are prominent features in CTE. The purpose of this study was to determine whether genetic variation in TMEM106B is associated with CTE risk, pathological features, and ante-mortem dementia. Eighty-six deceased male athletes with a history of participation in American football, informant-reported Caucasian, and a positive postmortem diagnosis of CTE without comorbid neurodegenerative disease were genotyped for rs3173615. The minor allele frequency (MAF = 0.42) in participants with CTE did not differ from previously reported neurologically normal controls (MAF = 0.43). However, in a case-only analysis among CTE cases, the minor allele was associated with reduced phosphorylated tau (ptau) pathology in the dorsolateral frontal cortex (DLFC) (AT8 density, odds ratio [OR] of increasing one quartile = 0.42, 95% confidence interval [CI] 0.22-0.79, p = 0.008), reduced neuroinflammation in the DLFC (CD68 density, OR of increasing one quartile = 0.53, 95% CI 0.29-0.98, p = 0.043), and increased synaptic protein density (ß = 0.306, 95% CI 0.065-0.546, p = 0.014). Among CTE cases, TMEM106B minor allele was also associated with reduced ante-mortem dementia (OR = 0.40, 95% CI 0.16-0.99, p = 0.048), but was not associated with TDP-43 pathology. All case-only models were adjusted for age at death and duration of football play. Taken together, variation in TMEM106B may have a protective effect on CTE-related outcomes.