Citations

AbstractIntroductionThe presentation, risk factors, and etiologies of white matter hyperintensities (WMH) in people exposed to repetitive head impacts are unknown. We examined the burden and distribution of WMH, and their association with years of play, age of first exposure, and clinical function in former American football players.MethodsA total of 149 former football players and 53 asymptomatic unexposed participants (all men, 45–74 years) completed fluid‐attenuated inversion recovery magnetic resonance imaging, neuropsychological testing, and self‐report neuropsychiatric measures. Lesion Segmentation Toolbox estimated WMH. Analyses were performed in the total sample and stratified by age 60.ResultsIn older but not younger participants, former football players had greater total, frontal, temporal, and parietal log‐WMH compared to asymptomatic unexposed men. In older but not younger former football players, greater log‐WMH was associated with younger age of first exposure to football and worse executive function.DiscussionIn older former football players, WMH may have unique presentations, risk factors, and etiologies.Highlights Older but not younger former football players had greater total, frontal, temporal, and parietal lobe white matter hyperintensities (WMH) compared to same‐age asymptomatic unexposed men. Younger age of first exposure to football was associated with greater WMH in older but not younger former American football players. In former football players, greater WMH was associated with worse executive function and verbal memory.

This scientific commentary refers to ‘Tau protein quantification in skin biopsies differentiates tauopathies from alpha-synucleinopathies’ by Vacchi et al. (https://doi.org/10.1093/brain/awac161).

Abstract Background and study aims Barrett’s esophagus (BE) is a precursor condition to esophageal adenocarcinoma (EAC), resulting in transformation of the squamous epithelium of distal esophagus to columnar-lined epithelium with intestinal metaplasia (IM). Liquid nitrogen spray cryotherapy (LNSC) is a non-contact method of BE eradication and has been used both as primary and salvage therapy. We conducted a systematic review and meta-analysis to assess the safety and efficacy of LNSC. Methods We searched multiple databases from inception through December 2021 to identify studies on use of LNSC for Barrett’s neoplasia. Pooled estimates were calculated using random-effects model and results were expressed in terms of pooled proportions with relevant 95 % confidence intervals (CIs) of complete eradication (CE) of dysplasia(D), high grade dysplasia (HGD) and IM. Results Fourteen studies with 707 patients were included in our final analysis. Overall pooled rates of CE-D, CE-HGD and CE-IM were 80.8 % (CI 77.4–83.8; I2 62), 90.3 % (CI 85.2–93.7; I2 33) and 55.8 % (CI 51.7–59.8; I2 73) with follow up ranging from 4.25 months to 69.7 months. In patients with follow up beyond 24 months, the rates of CE-D and CE-IM were 83.6 % (CI 77.6–88.2; I2 60) and 54.7 % (CI 47.6–61.6; I2 81). Among LNSC naïve patients with prior history of endoscopic resection, the rates were 79.9 % (CI 73.3–85.2; I2 50) and 67.1 % (CI 59.5–73.8; I2 0). Pooled rate of therapeutic failures, defined as lack of response to LNSC therapy, was 23.6 % (CI 19.4–28.3; I2 73). Post LNSC strictures and perforation pooled rates were 4 % and 0.8 %, respectively, which are similar to those previously reported for RFA. Conclusions Our analysis suggests that liquid nitrogen spray cryotherapy is an acceptable treatment for BE in both ablation naïve and experienced patients.

Lay SummaryWe demonstrate low rates of breakthrough coronavirus disease 2019 (COVID-19) infection and mild course of illness following severe acute respiratory syndrome coronavirus 2 vaccination in a large cohort of inflammatory bowel disease patients. Residence in southern United States and lower median anti-receptor binding antibody level were associated with development of COVID-19.

Abstract Brains of 42 COVID-19 decedents and 107 non-COVID-19 controls were studied. RT-PCR screening of 16 regions from 20 COVID-19 autopsies found SARS-CoV-2 E gene viral sequences in 7 regions (2.5% of 320 samples), concentrated in 4/20 subjects (20%). Additional screening of olfactory bulb (OB), amygdala (AMY) and entorhinal area for E, N1, N2, RNA-dependent RNA polymerase, and S gene sequences detected one or more of these in OB in 8/21 subjects (38%). It is uncertain whether these RNA sequences represent viable virus. Significant histopathology was limited to 2/42 cases (4.8%), one with a large acute cerebral infarct and one with hemorrhagic encephalitis. Case-control RNAseq in OB and AMY found more than 5000 and 700 differentially expressed genes, respectively, unrelated to RT-PCR results; these involved immune response, neuronal constituents, and olfactory/taste receptor genes. Olfactory marker protein-1 reduction indicated COVID-19-related loss of OB olfactory mucosa afferents. Iba-1-immunoreactive microglia had reduced area fractions in cerebellar cortex and AMY, and cytokine arrays showed generalized downregulation in AMY and upregulation in blood serum in COVID-19 cases. Although OB is a major brain portal for SARS-CoV-2, COVID-19 brain changes are more likely due to blood-borne immune mediators and trans-synaptic gene expression changes arising from OB deafferentation.

Abstract The Alzheimer disease (AD) neuropathological hallmarks amyloid β (Aβ) and tau neurofibrillary (NF) pathology have been reported in the olfactory bulb (OB) in aging and in different neurodegenerative diseases, which coincides with frequently reported olfactory dysfunction in these conditions. To better understand when the OB is affected in relation to the hierarchical progression of Aβ throughout the brain and whether OB pathology might be an indicator of AD severity, we assessed the presence of OB Aβ and tau NF pathology in an autopsy cohort of 158 non demented control and 173 AD dementia cases. OB Aβ was found in less than 5% of cases in lower Thal phases 0 and 1, in 20% of cases in phase 2, in 60% of cases in phase 3 and in more than 80% of cases in higher Thal phases 4 and 5. OB Aβ and tau pathology significantly predicted a Thal phase greater than 3, a Braak NF stage greater than 4, and an MMSE score lower than 24. While OB tau pathology is almost universal in the elderly and therefore is not a good predictor of AD severity, OB Aβ pathology coincides with clinically-manifest AD and might prove to be a useful biomarker of the extent of brain spread of both amyloid and tau pathology.

AbstractDecline of olfactory function is frequently observed in aging and is an early symptom of neurodegenerative diseases. As the olfactory bulb (OB) is one of the first regions involved by pathology and may represent an early disease stage, we specifically aimed to evaluate the contribution of OB pathology to olfactory decline in cognitively normal aged individuals without parkinsonism or dementia. This clinicopathological study correlates OB tau, amyloid β (Aβ) and α‐synuclein (αSyn) pathology densities and whole brain pathology load to olfactory identification function as measured with the University of Pennsylvania Smell Identification Test (UPSIT) and clinical data measured proximate to death in a large autopsy study including 138 cases considered non‐demented controls during life. Tau pathology was frequently observed in the OB (95% of cases), while both Aβ (27% of cases) and αSyn (20% of cases) OB pathologies were less commonly observed. A weak correlation was only observed between OB tau and olfactory performance, but when controlled for age, neither OB tau, Aβ or αSyn significantly predict olfactory performance. Moreover, whole brain tau and αSyn pathology loads predicted olfactory performance; however, only αSyn pathology loads survived age correction. In conclusion, OB tau pathology is frequently observed in normally aging individuals and increases with age but does not appear to independently contribute to age‐related olfactory impairment suggesting that further involvement of the brain seems necessary to contribute to age‐related olfactory decline.

Abstract A discussion and debate on the American Medical Informatics Association’s (AMIA) Ethical, Legal, and Social Issues (ELSI) Working Group listserv in 2021 raised important issues related to a forthcoming conference in Texas. Texas had recently enacted a restrictive abortion law and restricted voting rights. Several AMIA members advocated for a boycott of the state and the scheduled conference. The discussion led the AMIA Board of Directors to request that the organization’s Ethics Committee provide general guidance for principle-based venue selection. This document recommends overarching principles for the venue selection for future AMIA events and conferences. Discussions by the AMIA Board, the Ethics Committee, and the ELSI Working Group informed these recommendations, and this document on guiding principles was approved by the AMIA Board of Directors in April 2022.