162 patients with relapsed secondary central nervous system lymphoma (R-SCNSL) (median age, 65 years; male, 59.9%) including central nervous system (CNS)-only (n = 120) and concomitant CNS/systemic relapse (n = 42) were retrospectively analyzed. Overall, 21.9% of patients were classified as high risk according to the CNS International Prognostic Index (CNS-IPI). Several biological and clinical features were significantly associated with leptomeningeal involvement, including double- or triple-hit (DHL/THL) status, MYC rearrangement, negative BCL6 expression by IHC, bone marrow involvement, and concomitant R-SCNSL. Multivariable analysis showed that leptomeningeal involvement independently predicted inferior OS and was associated with a 98% increase in the hazard of death compared with parenchymal relapse (HR = 1.98, 95% CI: 1.20-3.26, p = 0.008). Based on anatomical localization, R-SCNSL was classified into four subtypes: parenchymal-only involvement (parenchymal-CNS [P-CNS], 68/42%) and parenchymal involvement plus systemic relapse (parenchymal-concomitant [P-concomitant], 17/10.5%); and leptomeningeal with or without parenchymal involvement (leptomeningeal-CNS [LM-CNS], 52/32.1%) and leptomeningeal with systemic relapse (leptomeningeal-concomitant [LM-concomitant], 25/15.4%). This anatomical classification significantly impacted OS and PFS (p < 0.001). Two-year OS and PFS were 58.2% and 29.1% for P-CNS, 32.4% and 17.7% for P-concomitant, 22% and 13.9% for LM-CNS, and 7.1% and 0% for LM-concomitant, respectively. ASCT showed a trend toward improved survival among patients with a response (CR/PR) in a 4-month landmark analysis. These findings support the clinical application of the anatomical classification in the management of R-SCNSL.

PurposeTo explore the relationship between systemic comorbidities and presenting tumor T category in patients with uveal melanoma.MethodsSingle-center, retrospective cohort study of patients with posterior uveal melanoma initially diagnosed between January 2000 and December 2016. Univariate and multivariate ordinal logistic regression analyses were performed to identify comorbidities associated with presenting tumor T category, as classified by AJCC criteria.ResultsInitial presenting AJCC T category was T1 in 190 (43%), T2 in 130 (29%), T3 in 89 (20%), and T4 in 38 (9%). The most common comorbidities present were hypertension (250 patients, 56%), hyperlipidemia (211, 47%), obesity (137, 31%), and diabetes mellitus (87, 19%). Of these, obesity (p = 0.034), hypertension (p = 0.017), and diabetes mellitus (p < 0.001) were associated with earlier presenting T category on univariate ordinal logistic regression. After multivariate regression, only diabetes mellitus (p = 0.01) and obesity (p = 0.04) remained significantly associated with earlier T category on initial presentation.ConclusionAmong patients presenting with uveal melanoma, diabetes mellitus and obesity were associated with earlier presenting T category, which could reflect earlier detection of uveal melanoma in patients undergoing annual diabetic retinopathy screening examinations or having more frequent contact with the healthcare system. Larger studies should further explore this association and examine the utility of increased ocular screening in early detection of uveal melanoma.

Disturbances within the cerebrovascular system substantially contribute to the pathogenesis of age-related cognitive impairment and Alzheimer’s disease (AD). Cerebral amyloid angiopathy (CAA) is characterized by the deposition of amyloid-β (Aβ) in the leptomeningeal and cortical arteries and is highly prevalent in AD, affecting over 90

The immune system is substantially involved in the development and progression of age-related cognitive decline and Alzheimer’s disease (AD). As genetic and environmental factors interactively impact these conditions, we investigated how risk factors such as APOE genotype, age, and sex influence immune activation markers and AD biomarkers in cerebrospinal fluid (CSF) in elderly individuals enrolled in the Mayo Clinic Study of Aging cohort. Among cognitively unimpaired individuals aged over 65 at the baseline visit (N=298), we measured 365 CSF immune activation markers using the proximity extension assay. We found that age, sex, and diabetes status are associated with altered CSF levels of immune activation markers independently of other factors. For CSF AD biomarkers, we observed significant positive correlations between age and total tau, phosphorylated tau-181 (p-tau181), neurofilament light (NfL), and YKL40. APOE4 was also associated with lower Aβ42 and higher SNAP25 in CSF. We further examined whether baseline visit variables can predict cognitive decline, represented by the conversion from CDR=0 to CDR>0. We found that age, Aβ42, NfL, and REG4 were independently correlated with CDR conversion risk. When the cohort was dichotomized by their median values, older participants with lower Aβ42, higher NfL, and higher REG4 at baseline developed cognitive impairment during the follow up with a c-index of 0.762 while age alone had a c-index of 0.699. Together, our results suggest that assessing CSF immune activation markers and AD biomarkers can improve the prediction of cognitive impairment risk in the elderly.

BACKGROUND:Therapeutic development for frontotemporal dementia (FTD) is hindered by the lack of biomarkers that inform susceptibility/risk, prognosis, and the underlying causative pathology. Blood glial fibrillary acidic protein (GFAP) has garnered attention as a FTD biomarker. However, investigations of GFAP in FTD have been hampered by symptomatic and histopathologic heterogeneity and small cohort sizes contributing to inconsistent findings. Therefore, we evaluated plasma GFAP as a FTD biomarker and compared its performance to that of neurofilament light (NfL) protein, a leading FTD biomarker. METHODS:We availed ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) study resources to conduct a comprehensive cross-sectional and longitudinal examination of the susceptibility/risk, prognostic, and predictive performance of GFAP and NfL in the largest series of well-characterized presymptomatic FTD mutation carriers and participants with sporadic or familial FTD syndromes. Utilizing single molecule array technology, we measured GFAP and NfL in plasma from 161 controls, 127 presymptomatic mutation carriers, 702 participants with a FTD syndrome, and 67 participants with mild behavioral and/or cognitive changes. We used multivariable linear regression and Cox proportional hazard models adjusted for co-variates to examine the biomarker utility of baseline GFAP and NfL concentrations or their rates of change. RESULTS:Compared to controls, GFAP and NfL were elevated in each FTD syndrome but GFAP, unlike NfL, poorly discriminated controls from participants with mild symptoms. Similarly, both baseline GFAP and NfL were higher in presymptomatic mutation carriers who later phenoconverted, but NfL better distinguished non-converters from phenoconverters. We additionally observed that GFAP and NfL were associated with disease severity indicators and survival, but NfL far outperformed GFAP. Nevertheless, we validated findings that the GFAP/NfL ratio may discriminate frontotemporal lobar degeneration with tau versus TDP-43 pathology. CONCLUSIONS:Our head-to-head comparison of plasma GFAP and NfL as biomarkers for FTD indicate that NfL consistently outmatched GFAP as a prognostic and predictive biomarker for participants with a FTD syndrome, and as a susceptibility/risk biomarker for people at genetic risk of FTD. Our findings underscore the need to include leading biomarkers in investigations evaluating new biomarkers if the field is to fully ascertain their performance and clinical value.

The kinase–ligase pair PINK1–PRKN initiates mitophagy by recognizing and selectively tagging worn-out and dysfunctional mitochondria with phosphorylated ubiquitin (pS65-Ub) to facilitate their elimination via autophagy. In human autopsy brains, the number of pS65-Ub positive cells increases with age but is also associated with Lewy body (LB), neurofibrillary tangles (NFT), and senile plaque (SP) burden. Through a recent genome-wide association study, we identified two genetic modifiers of pS65-Ub levels, APOE4 and ZMIZ1 rs6480922. While LB, NFT, and SP pathologies often coexist in Lewy body dementia (LBD), it is unclear how genetic factors and comorbid neuropathologies interact to impact mitophagy in vulnerable brain regions. We therefore measured levels of the age and disease marker pS65-Ub in the hippocampus and amygdala of 371 LBD cases. Significant and independent associations with pS65-Ub levels were observed for each of the three pathologies LB, NFT, and SP in both regions, and the presence of APOE4 significantly strengthened the association between NFT and pS65-Ub in the hippocampus. While no interaction between LB and SP pathologies was observed regarding association with pS65-Ub, a significant interaction between LB and NFT pathologies on pS65-Ub accumulation was found in the amygdala, which was primarily observed in carriers of the minor allele of ZMIZ1 rs6480922. In summary, our study revealed complex interactions between LB pathology, NFT pathology, and genetic mitophagy modifiers in LBD brains, highlighting potential convergent molecular mechanisms underlying α-synuclein- and tau-associated mitophagy alterations.

Dermatological health-related quality of life (HRQoL) in solid organ transplant recipients (SOTRs), often affected by skin cancer, has been insufficiently explored. This study aimed to evaluate the impact of skin cancer on quality of life (QoL) in SOTRs and to compare HRQoL measures between SOTRs with and without skin cancer. This cross-sectional study (June 2023–March 2024) assessed adult SOTRs using the Dermatology Life Quality Index (DLQI) and Skindex-29 questionnaires. For SOTRs with keratinocyte carcinoma (KC), the Basal and Squamous Cell Carcinoma Quality of Life (BaSQoL) questionnaire was also administered. A total of 150 adult SOTRs were included, with 82 having developed post-transplant skin cancer, including melanoma and KCs. DLQI scores were higher in SOTRs with skin cancer, however, the difference was not statistically significant (P ≥ 0.065). SOTRs with skin cancer had higher total Skindex-29 scores (P = 0.012) and “emotion” subscale scores (P = 0.0049), indicating a negative impact on QoL. BaSQoL scores showed a moderate negative effect on QoL, with a higher number of KCs correlating with lower QoL (P < 0.05). Female gender was associated with higher DLQI and BaSQoL diagnosis and treatment scores (P < 0.05). SOTRs with skin cancer had lower QoL, with greater cancer burden linked to worse outcomes. Female gender was also associated with lower QoL. Tailored management strategies are crucial for this population.

INTRODUCTION:The United States has experienced a notable increase in opioid abuse over the past several years, with orthopaedic surgeons reported as the third-highest prescribers by specialty. Several studies have addressed opioid use after major orthopaedic procedures but largely focused on prescribing practices. There is limited data on the utility of adding adductor canal pain catheters to multimodal regimens following total knee arthroplasty for improved pain control and reduced opioid dependence. The purpose of this preliminary study was to compare single-shot adductor canal blocks to continuous infusion or intermittent bolus catheters, evaluating postoperative pain levels and duration of opioid use. METHODS:Sixty opioid-naive patients participated in a prospective, randomized, double-blinded, placebo-controlled trial. Following total knee arthroplasty, patients were randomized into one of three cohorts based on preoperative pain levels: (1) single-shot adductor canal block with placebo catheter, (2) continuous infusion catheter, or (3) intermittent bolus catheter. Postoperative protocols were similar except for the catheter. Patient outcomes were recorded for 60 days postoperatively. RESULTS:We found no difference in length of stay, oral morphine equivalents, use of on-demand medication, or pain scores (all P > 0.05) between the groups. Although the single-shot cohort trended toward a longer duration of opioid use (median 21 days) compared with the catheter groups (median 14 days for both), this did not approach statistical significance ( P = 0.59). We found no difference in Knee Injury and Osteoarthritis Outcome Score Jr scores between the groups at 30 or 60 days postoperatively (all P > 0.05). CONCLUSION:In our preliminary study, we found no differences in clinical outcomes, pain scores, or patient-reported scores between a single-shot adductor canal block, a continuous infusion adductor canal catheter, and an intermittent bolus adductor catheter following total knee arthroplasty. Larger studies are needed to more definitively assess differences in outcomes between the treatment groups, particularly in the opioid-tolerant population.

PurposeTo describe the clinical characteristics, histopathologic subtype distribution, treatment, and outcomes of patients with primary orbital lymphoma.Major FindingsThere were 126 biopsy-confirmed cases of primary orbital lymphoma, with 81 (64.3%) female and 110 (87.3%) white. The average age at diagnosis was 62.7 ± 13.9 years. There were 26 (20.6%) cases with bilateral involvement. The most frequent lymphoma subtype was MALT lymphoma (N = 76, 60.3%), followed by diffuse large B-cell lymphoma (N = 18, 14.3%) and follicular lymphoma (N = 12, 9.5%). Prognosis was generally favorable, as local recurrence occurred in only 14 (11.1%) patients and final best corrected visual acuity (BCVA) loss of >1 line was seen in 30 (28.0%) patients. Bilateral lymphoma and advanced stage (Ann Arbor Stage III or IV) at presentation were associated with increased risk of local recurrence (p = 0.0025, p = 0.049). Improved disease-specific survival was associated with diagnosis at Stage I or II (p = 0.013), MALT subtype (p = 0.034), or lack of chemotherapy requirement as primary treatment (p = 0.0073).ConclusionsIn this single center academic cohort, MALT lymphoma subtype was most common. Overall orbital recurrence frequency was low, and bilateral lymphoma and advanced stage were associated with increased risk of local recurrence. MALT lymphoma subtype was associated with improved disease-specific survival. Long-term follow-up showed that most patients retained good visual acuity in the affected eye(s).

INTRODUCTION:Phosphorylated ubiquitin (p-S65-Ub) is generated during PINK1-PRKN mitophagy as a specific marker of mitochondrial damage. Despite the widespread deposition of p-S65-Ub in aged and diseased human brain, the genetic contribution to its accumulation remains unclear. METHODS:To identify novel mitophagy regulators, we performed a genome-wide association study using p-S65-Ub level as a quantitative trait in 1012 autopsy-confirmed Lewy body disease (LBD) samples. RESULTS:We identified a significant genome-wide association with p-S65-Ub for rs429358 (apolipoprotein E ε4 [APOE4]) and a suggestive association for rs6480922 (ZMIZ1). APOE4 was associated with higher p-S65-Ub levels and greater neuropathological burden. Functional validation in mouse and human induced pluripotent stem cell (iPSC) models confirmed APOE4-mediated mitophagy alterations. Intriguingly, ZMIZ1 rs6480922 was associated with lower p-S65-Ub levels, reduced neuropathological load, and increased brain weight, indicating a potential protective role. DISCUSSION:Our findings underscore the importance of mitochondrial quality control in LBD pathogenesis and nominate regulators that may contribute to disease risk or resilience. HIGHLIGHTS:p-S65-Ub levels were used as a quantitative marker of mitochondrial damage. A GWAS identified two genetic variants that modify mitophagy in LBD autopsy brain. APOE4 was associated with increased p-S65-Ub accumulation and neuropathology. APOE4 altered mitophagy via pathology-dependent and pathology-independent mechanisms. ZMIZ1 was linked to reduced p-S65-Ub and neuropathology indicative of protection.

BACKGROUND Flap repair provides unique advantages in facial reconstruction but still carries the potential for undesirable postoperative cosmetic changes. OBJECTIVE The aims of this study were to describe postoperative vascular outcomes of patients undergoing flap repairs after Mohs micrographic surgery on facial tumors and to assess associations of baseline characteristics with outcomes. MATERIALS AND METHODS In this study, 7 dermatologists and 1 physician assistant in dermatology assessed preoperative and postoperative photographs of 57 patients who underwent facial Mohs micrographic surgery, evaluating vascular and pigment outcomes and number of telangiectasias. RESULTS There was a significant difference in number of telangiectasias according to body location ( p = .002), where the number of telangiectasias was highest for nose surgery. CONCLUSION These data suggest that nasal flap repairs are associated with increased postoperative vascular changes. This highlights an opportunity for improved preoperative patient counseling and possible early laser treatment after nasal Mohs micrographic surgery.

Studies assessing genetic associations with neuropathological features in Lewy body disease (LBD) have been limited to candidate gene investigations, and therefore, information is lacking regarding the genetic architecture of the neuropathology of LBD. In the current study, we examined a large series of neuropathologically confirmed LBD cases (n = 980 in the discovery series, n = 503 in the replication series) and performed genome-wide association studies of 11 different neuropathological outcome measures. The 11 neuropathological outcomes included Braak neurofibrillary tangle (NFT) stage, Thal amyloid phase, LBD subtype, Lewy body (LB) counts in five different brain regions, dorsolateral and ventromedial putaminal tyrosine hydroxylase immunoreactivity and neuronal loss in the ventrolateral part of the substantia nigra. Associations between variants and outcomes were assessed using regression models appropriate for the nature of the given neuropathological outcome and that were adjusted for age at death, sex and top principal components of genetic data. In the discovery series, APOE rs429358 (i.e. APOE ε4) was associated with a greater severity of each of Braak NFT stage [odds ratio (OR) = 3.07, P = 2.34 × 10-32], Thal amyloid phase (OR = 3.57, P = 3.28 × 10-29) and LBD subtype (OR = 1.78, P = 9.85 × 10-9), with similar findings observed in the independent replication series (Braak NFT stage, OR = 2.30, P = 2.70 × 10-11; Thal amyloid phase, OR = 3.17, P = 6.39 × 10-18; LBD subtype, OR = 2.68, P = 3.85 × 10-10). In the subgroup of cases with lower levels of Alzheimer's disease pathology (Braak NFT stage ≤ III and Thal amyloid phase ≤2), there was a strong association between APOE rs429358 and LBD subtype even when adjusting for Braak stage and Thal phase in the discovery series (n = 218, OR = 2.47, P = 0.007) and the replication series (n = 141, OR = 3.60, P = 0.006). Although additional genome-wide significant associations were identified in the discovery series between LINC01581/MCTP2 rs547411734 and lower middle frontal LB counts, between TLE3 rs3743309 and lower cingulate LB counts, and between GRIN2A/ATF7IP2 rs1097915 and lower parahippocampal LB counts, these findings were not observed in the replication series. Our results indicate that the APOE ε4 allele is the most prominent genetic determinant of severity of neuropathology in LBD. These findings represent a key step forward in our understanding of genetic drivers of neuropathological features in LBD. Future studies utilizing meta-analytical approaches will be important to more precisely assess other associations that were not quite genome-wide significant in the discovery series.

INTRODUCTION:Parkinson's disease (PD) is characterized by substantial clinical and genetic heterogeneity. The biological mechanisms underlying different clinical presentations remain unclear. This study aimed to investigate if distinct biological pathways, represented by pathway-specific polygenic risk scores (PRS's), differ between PD clinical subtypes. METHODS:The study included 799 PD patients classified into four empirical PD motor subtypes: tremor-dominant (TD) (n = 345), akinetic-rigid (AR) (n = 227), gait-difficulty (n = 82) and mixed (n = 145). Genotyping was performed using the Illumina NeuroChip array, with data imputed via the TOPMed Imputation Server. A total of 7,918,344 variants were included in the final analysis. Ten PRS's were constructed, including overall PD risk, adaptive immunity, alpha-synuclein, innate immunity, lysosomal, endocytic membrane trafficking, mitochondrial, microglial, monocyte, and Alzheimer's disease pathways. Linear regression models adjusted for age, sex, disease duration, and genetic principal components were used to compare PRS's between PD subtypes. RESULTS:After correcting for multiple testing (P < 0.0125 considered significant), a significantly higher adaptive immunity PD PRS was observed for the AR subtype compared to other subtypes (β: 0.04, P = 0.011). Nominally significant (P < 0.05) associations included an increased overall PD PRS for the AR subtype (β: 0.18, P = 0.041) and a lower adaptive immunity PD PRS for the TD subtype (β: -0.03, P = 0.041). CONCLUSION:Our findings suggest distinct genetic risk profiles across PD motor subtypes, particularly within immune-related pathways. These results support viewing PD as a syndrome driven by multiple distinct pathomechanisms, underscoring the need for subtype-specific biomarkers, more personalized clinical trial designs, and targeted therapeutic strategies in PD management.

Objective: To assess the accuracy of patients' personal continuous glucose monitors (CGMs) worn in the hospital and accuracy correlation with laboratory values and vital signs and to compare CGM glucometric data with data from published literature and guidelines. Method: We enrolled adult patients with diabetes mellitus wearing outpatient-inserted CGMs at the time of hospital admission to a noncritical setting. CGM readings were paired within 5 min with point of care (POC) glucometers and laboratory (Lab) blood glucose levels. CGM accuracy was expressed using mean absolute relative difference (MARD) and Clarke Error Grids. CGM accuracy variation with labs and vital signs was analyzed with Spearman's correlation method. Results: For 188 hospitalizations, we analyzed 3316 CGM-POC pairs from 101 patients (56 with Dexcom® sensors and 45 with Abbott's FreeStyle Libre® sensors) and 771 CGM-Lab pairs for 97 patients. For CGM-POC pairs, MARD was 13.7%, 14.4%, and 11.8% for all sensors, Dexcom, and Libre sensors, respectively. MARD was 22.6% for POC glucose <70 mg/dL. For CGM-Lab pairs, MARD was 13.6%, 12.7%, and 15.4% for all sensors, Dexcom, and Libre sensors, respectively. Of CGM-POC pairs, 98.7% and 98.8% of CGM-Lab pairs were in zones A and B of Error Grid Analysis. There was no correlation between ARD and daily mean arterial blood pressure, hemoglobin level, glomerular filtration rate, and pulse oximetry. CGMs' time below range (TBR), time in range (TIR), and time above range were 2.2% (standard deviation [SD]: 4.7%), 58.7% (SD: 22.5%), and 39.9% (SD: 23.4%), respectively. The coefficient of variation was 31.2%. Conclusion: Except for hypoglycemia ranges, patients' personal CGMs had adequate accuracy for glucose monitoring in the hospital. Vital signs and Lab values did not interfere with CGM accuracy. The TBR and glucose variability were low, better than outpatient recommendations. TIR was in line with inpatient consensus guidelines, and "glucometrics" were comparable with reports for hospital inserted sensors.

Background/objectives: Choroidal nevus necessitates regular monitoring due to its potential for malignant transformation. We identified features associated with lost to follow-up (LTFU), delayed follow-up (DFU), and appropriate follow-up (AFU) in choroidal nevus patients. Subjects/methods: This retrospective cohort study analysed 825 adults diagnosed with choroidal nevus between January 1, 2006, and December 31, 2015, in Olmsted County, Minnesota. Patient demographics, tumour features, and clinical outcomes were assessed according to follow-up status. Results: Among the patients, 82 (9.9%) were LTFU, 317 (38.4%) had DFU, and 426 (51.6%) had AFU. Comparing groups (LTFU vs. DFU vs. AFU), LTFU patients were younger (mean age 44.5 vs. 53.3 vs. 59.7 years, p < 0.001) and primarily diagnosed by optometrists (64.6% vs. 64.4% vs. 41.1%, p < 0.001) on routine visits (56.1% vs. 69.7% vs. 45.8%, p < 0.001). They had lower Charlson comorbidity index (0.4 vs. 0.5 vs. 0.7, p = 0.005) and less systemic cancer history (9.5% vs. 15.7% vs. 22.7%, p = 0.013). LTFU and DFU had better visual acuity (>20/50) compared to AFU (93.9% vs. 94.6% vs. 88.5%, p = 0.019). AFU had larger tumour dimensions (basal diameter: 2.5 mm vs. 2.3 mm vs. 2.8 mm, p = 0.003; thickness: 0.1 mm vs. 0.1 mm vs. 0.2 mm, p < 0.001). More LTFU patients had a mean initial recommended follow-up time of 12 months compared to DFU and AFU (80.5% vs. 78.9% vs. 74.2%, p < 0.001). Conclusions: Factors associated with LTFU in choroidal nevus patients include younger age, lower comorbidity index, absence of cancer history, optometrist diagnosis, routine visit diagnosis, better visual acuity, less suspicious tumour features, and longer follow-up recommendation.

Historically, cancers diagnosed via the emergency department (ED) portend a poor prognosis. Recent data from the United States are sparse, and analyses of cancers detected in the years following ED visits are lacking. Thus, we analyzed data from nine rural U.S. Midwest counties included within the population-based Rochester Epidemiology Project (2015-2021). Participants without a history of cancer (N = 42,074) who did not receive ED care were matched 1:1 to ED participants on the date of ED visit, age, sex, race, ethnicity, and county of residence. Analyses were restricted to participants with records ≤2 years prior to ED or index visit and ≥30 days after. HRs and 95% confidence intervals (CI) comparing cancer incidence and deaths among ED and non-ED participants were estimated from Cox proportional hazards regression models, either unadjusted or adjusted for covariates. Cumulative cancer incidence curves accounting for competing risks of death and survival (all cause and cancer-specific) were estimated. The median follow-up was 6.3 years, with 2,719 (6.46%) cancers diagnosed among ED participants and 3,139 (7.46%) among non-ED participants. ED participants experienced lower cancer risk overall (HRAdjusted = 0.70; 95% CI, 0.66-0.74; P = 8.89 × 10-31), specifically for breast cancer, prostate cancer, melanoma, and secondary cancers. Cancer-specific mortality was higher among ED participants (HRAdjusted = 1.76; 95% CI, 1.49-2.08; P = 3.62 × 10-11). Compared with non-ED participants, ED participants experienced a lower incidence of cancer but higher overall cancer-specific mortality, suggesting that subsets of ED patients may benefit from postvisit preventive interventions. PREVENTION RELEVANCE:This cohort analysis shows that cancer incidence over 6 years was lower among participants after an ED visit than among matched non-ED participants, whereas cancer-specific mortality was higher in the ED group (HRAdjusted = 1.76; 95% CI, 1.49-2.08; P = 3.62 × 10-11), suggesting the potential benefit of preventive interventions.

Rare and common GBA variants are risk factors for both Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). However, the degree to which GBA variants are associated with neuropathological features in Lewy body disease (LBD) is unknown. Herein, we assessed 943 LBD cases and examined associations of 15 different neuropathological outcomes with common and rare GBA variants. Neuropathological outcomes included LBD subtype, presence of a high likelihood of clinical DLB (per consensus guidelines), LB counts in five cortical regions, tyrosine hydroxylase immunoreactivity in the dorsolateral and ventromedial putamen, ventrolateral substantia nigra neuronal loss, Braak neurofibrillary tangle (NFT) stage, Thal amyloid phase, phospho-ubiquitin (pS65-Ub) level, TDP-43 pathology, and vascular disease. Sequencing of GBA exons revealed a total of 42 different variants (4 common [MAF > 0.5