Citations

Tissue harmonic and spatial compound imaging, widely used US techniques, improve image quality by reducing noise and artifacts through complementary mechanisms.

Objective To investigate sex differences in Alzheimer's disease (AD) related pathology among autopsy-confirmed Parkinson's disease (PD) cases. Background AD and PD frequently co-occur in older adults, yet the influence of sex on AD pathology in the context of PD remains unexplored. Methods All subjects were enrolled in the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) and Brain and Body Donation Program (BBDP) and had annual standardized research clinical assessments by neuropsychologists, subspecialty behavioral and movement disorders neurologists, as well as comprehensive neuropathological examinations after death. Results Among 230 autopsy-confirmed PD cases, females exhibited greater amyloid plaque pathology burden than males, regardless of a co-occurring AD diagnosis. Specifically, females with PD had significantly higher mean cortical total plaque scores (mean 6.5/15 vs. 4.9/15, p = 0.045) and greater CERAD neuritic plaque density (mean 1.7/3 vs. 1.3/3, p = 0.035). Females were also more likely to have a higher cortical plaque burden (plaque total ≥ 5: 56.8% vs. 39.7%, p = 0.015). In multivariable logistic regression models, female subjects showed greater than twice the odds of having an amyloid plaque burden ≥5 compared to males (OR = 2.18; 95% CI = 1.17–4.06; p = 0.014), when controlling for ApoE ε4 status, Lewy body density score, and age at death. Conclusions Female sex is associated with increased amyloid plaque pathology in PD, independent of ApoE ε4 status. These findings highlight a sex-specific vulnerability to AD pathology in PD patients and support the need for sex-informed approaches to reseach in mixed neurodegenerative disease.

Acute cholecystitis affects ∼200,000 individuals annually in the United States, with laparoscopic cholecystectomy as the gold standard treatment. However, in high-risk surgical candidates, alternative drainage methods are necessary. Percutaneous transhepatic gallbladder drainage (PT-GBD) has traditionally served as the primary alternative intervention, offering rapid decompression, but is limited by a negative impact on the patient’s quality of life, the risk of long-term or even permanent tube placement, adverse events, and high recurrence rates. Endoscopic approaches, such as endoscopic transpapillary gallbladder drainage (ET-GBD) and, more recently, endoscopic ultrasound-guided gallbladder drainage (EUS-GBD), have emerged as viable alternatives to PT-GBD. EUS-GBD, first introduced in 2007, offers technical and clinical outcomes comparable to PT-GBD with fewer adverse events, shorter hospital stays, and lower rates of recurrence. The introduction of lumen-apposing metal stents (LAMS) has revolutionized EUS-GBD, simplifying deployment and enabling subsequent internal gallbladder access, which allows additional interventions such as cholecystoscopy and stone removal. EUS-GBD is now supported by international guidelines, and 1 device has achieved FDA approval for the management of acute cholecystitis in nonsurgical candidates. Proper patient selection is essential, guided by multidisciplinary evaluation, with EUS-GBD contraindicated in specific scenarios such as gallbladder perforation, coagulopathy, and large-volume ascites. Technical considerations include choice of access site (transgastric versus transduodenal), stent type, and procedural route [direct (freehand) or wire-guided]. Postprocedural care and stent management remain variable and nonstandardized. Emerging data suggest that interval cholecystectomy can still be performed safely after EUS-GBD. As adoption of EUS-GBD with LAMS expands, structured training and standardization of practice are crucial to optimizing outcomes.

Importance In vivo biomarkers for detecting neuropathologies from repetitive head impacts (RHI), including chronic traumatic encephalopathy (CTE), are needed. Objective To evaluate the utility of plasma phosphorylated tau 217 (p-tau217), assess its performance as a beta-amyloid (Aβ) biomarker in participants with RHI exposure at risk for CTE, and explore concordance with CTE neuropathology in a postmortem subsample. Design, Setting, and Participants This longitudinal, multicenter, case-control study used data from the Diagnostics, Imaging, and Genetics Network for the Objective Study and Evaluation of CTE (DIAGNOSE CTE) Research Project, collected from September 2016 to October 2023. Participants were former American football players (case participants) and asymptomatic men unexposed to RHI (control participants). A subsample had available neuropathologic data. Exposures RHI, traumatic encephalopathy syndrome (TES) diagnoses, and levels of CTE certainty. Main Outcomes and Measures Plasma p-tau217 (classified as positive [≥0.63 pg/mL], intermediate [0.40-0.62 pg/mL], and negative [<0.40 pg/mL]), Aβ–positron emission tomography (PET; 18 F-florbetapir; with Aβ-positive defined as a standardized uptake value ratio [SUVR] ≥1.10), and tau-PET ( 18 F-flortaucipir). TES diagnoses were assigned by multidisciplinary consensus conference. Analyses of postmortem brains controlled for age, race, and APOE ε4 status. Results Among 231 participants (mean [SD] age, 57.75 [8.25] years), 177 were former football players (117 professional and 60 college) and 54 were unexposed participants. Former football players had higher baseline mean (SD) p-tau217 concentrations than unexposed participants (0.35 [0.26] pg/mL vs 0.27 [0.14] pg/mL; P = .008), although this was driven by a higher proportion of Aβ-PET–positive participants among former players. Plasma p-tau217 increased over time across the sample (B = 0.207 [95% CI, 0.117-0.298]; P < .001), with no significant time × exposure group interactions. Among football players, p-tau217 showed no time × group interactions with TES diagnosis, TES-CTE certainty, or RHI metrics. Higher p-tau217 concentration correlated with higher global Aβ-PET SUVR (B = 0.058 [95% CI, 0.053-3.501; P = .01), with a few discordant cases (5 participants were p-tau217–negative and Aβ-PET–positive; 7 participants were p-tau217–positive and Aβ-PET–negative). P-tau217 had similar areas under the curve for projecting Aβ-PET positivity as cerebrospinal fluid (CSF) p-tau181/Aβ42 and CSF Aβ40/42 measures (p-tau217: AUC, 0.88 [95% CI, 0.80-0.96]; CSF p-tau181/Aβ42: AUC, 0.89 [95% CI, 0.79-1.00]; CSF Aβ40/42: AUC, 0.85 [95% CI, 0.72-0.98]). Among 9 brain donors, 6 had CTE (stages II-IV; none with Alzheimer disease). Seven had negative or intermediate p-tau217, concordant with Aβ-PET. Two p-tau217 outliers with stage III CTE had normal concentrations upon additional testing. Conclusions and Relevance The findings of this study suggest that plasma p-tau217 concentration is unlikely to be useful for the detection of CTE, but it does show utility for ruling out Aβ pathology in participants at risk for CTE.

BACKGROUND: Acoramidis achieves near-complete (≥90%) transthyretin stabilization and is approved to reduce cardiovascular-related mortality and hospitalization in transthyretin amyloid cardiomyopathy. Its effects on kidney function are not well characterized. METHODS: Data from randomized phase 2 (N=49) and phase 3 (N=632) studies in transthyretin amyloid cardiomyopathy were included. The estimated glomerular filtration rate (eGFR) slope was generated using a linear spline mixed-effects model. The urinary albumin-to-creatinine ratio was measured longitudinally. Relationships between changes in kidney function and clinical outcomes were explored using Cox proportional hazards models. RESULTS: Acoramidis initiation resulted in a modest acute dip in eGFR that was dose-dependent, reversible, and not associated with adverse kidney-related events. At Day 28, the mean (±SE) dip in eGFR from baseline with acoramidis was 8.5±0.48 mL/min per 1.73 m 2 ; the placebo-corrected reduction in the urinary albumin-to-creatinine ratio was 15.5% (95% CI, 0.4%–28.4%; P =0.044). The rate of decline in kidney function (chronic eGFR slope) was significantly improved with acoramidis versus placebo (−1.01 versus −3.48 mL/min per 1.73 m 2 per year; P <0.001), and the reduction in the urinary albumin-to-creatinine ratio was sustained (13.7% [95% CI, 1.7%–24.2%]; P =0.026) over time. Concomitant tafamidis use did not influence the chronic eGFR slope in either arm. Comparing acoramidis versus placebo subgroups with acute eGFR dips ≥ the median (4.89 mL/min per 1.73 m 2 ) favored acoramidis for all-cause mortality or cardiovascular-related hospitalization (hazard ratio, 0.42 [95% CI, 0.22–0.78]; P =0.006; P interaction=0.043) and cardiovascular-related hospitalization (hazard ratio, 0.34 [95% CI, 0.17–0.66]; P =0.002, P interaction=0.025). Within the placebo arm, eGFR dips portended worse outcomes. CONCLUSIONS: Acoramidis initiation resulted in an acute dip in eGFR and reductions in both the chronic eGFR slope and urinary albumin-to-creatinine ratio versus placebo without adverse kidney-related events. Acoramidis effects on kidney function may be mediated through direct kidney-protective hemodynamic effects. Importantly, the acute dip in eGFR was associated with a reduced risk of adverse clinical outcomes within the first year. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT03458130, NCT03536767, NCT03860935, NCT04988386.

Abstract Background Inflammatory bowel disease (IBD) can lead to a hypercoagulable state, particularly at initial diagnosis. Consequently, venous thromboembolism (VTE) represents a serious complication associated with IBD. For children, the risk of VTE near the time of IBD diagnosis has not yet been quantified, and guidance for VTE prophylaxis remains unclear. Methods This multisite matched case-control study examined pediatric patients with a new diagnosis of IBD from 2019-2024. Cases were those who developed VTE ≤30 days prior or ≤90 days post IBD diagnosis. Controls were newly diagnosed IBD patients without VTE. Each case was matched to 2-6 controls based on IBD subtype and age at IBD diagnosis. Demographics, laboratory values, prothrombotic risk factors and treatments were compared between matched cases and controls using conditional logistic regression stratified, by case sets. Results Study subjects included 15 cases and 52 controls, resulting in 70 matched pairs. Factors associated with early VTE included lower hemoglobin (P = .003), lower albumin (P = .002), corticosteroids use (P = .01), central line (P = .002), and any surgery ≤90 days post IBD diagnosis (P = .001). No association with VTE was detected for platelets, C-reactive protein, fecal calprotectin, family history of IBD or body mass index. Conclusions Albumin, hemoglobin, steroid use, central line, and any surgery ≤90 days post IBD diagnosis were associated with early VTE. These risk factors may be used in a future prediction model to stratify newly diagnosed pediatric IBD patients by their risk for early VTE development.