Citations

Abstract Importance Decline in olfactory function may be used as a predictor of cognitive decline, to enhance early detection models, improve risk stratification, and enable early intervention. Objective To assess the longitudinal association between olfactory decline, cognitive decline, and postmortem neuropathology. Design, setting and participants Retrospective longitudinal analysis with clinicopathological correlations of a prospective population-based cohort study using data from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) and its Brain and Body Donation Program. Participants included cognitively unimpaired individuals without parkinsonism that converted to mild cognitive impairment (MCI) and/or dementia or remained cognitively stable. Main Outcomes and Measures longitudinal change in olfaction, neuropsychiatric symptoms, motor function and memory, conversion to MCI/dementia, postmortem neuropathology Results Over a mean follow-up period of 7.7 ± 5.4 years, out of 922 participants who were cognitively unimpaired at the first cognitive conference, 643 remained cognitively unimpaired, 279 converted to MCI, and 82 developed dementia. Of these, 633 individuals had at least 2 olfactory tests. Converters showed reduced olfactory function (t=-12.6, p <0.0001), faster progression in neuropsychiatric symptom burden (t=3.42, p < 0.001), and faster decline in memory (t= -7.33, p <0.0001) prior to conversion while no significant differences were observed in motor scores between converters and non-converters. Using ROC analysis, olfactory decline, increased neuropsychiatric symptom burden, as well as motor and memory decline predicted conversion to MCI with a consistent accuracy of ∼ 70% up to 5 years before conversion, while UPSIT alone had an accuracy of ∼ 60%. Longitudinal decline in olfaction was associated with a higher burden of a-synuclein (t= -8.21, p <0.0005), tau tangle (t= -2.66, p < 0.01) and amyloid plaque burden (t= -2.85, p < 0.005) and a faster decline over time was associated with a higher burden of tau (t=5.66, p<0.0001). Conclusions and Relevance A reduction in olfactory identification ability is observed up to a decade prior to conversion to MCI and is associated with underlying burden of neuropathology markers, underscoring the value of incorporating olfactory testing in cognitively unimpaired individuals to identify those at-risk of future cognitive decline.

Abstract Skin biopsies analyzed with α-synuclein seed amplification assays (SAAs) are a simple way to clinically interrogate the presence of α-synuclein aggregates. We determined the accuracy of skin biopsy SAA in predicting the clinical diagnoses of Parkinson disease (PD), PD with dementia (PDD) and dementia with Lewy bodies (DLB). Blinded SAAs were performed in 3 independent laboratories. Subjects diagnosed with PD, PDD and DLB were analyzed together as group 1, clinically unaffected subjects as group 2 and those with risk factors for LBD as group 3. Punch biopsies were taken from the posterior neck and analyzed by the 3 labs in 6 separate SAAs. Pairwise agreement between labs and assays ranged from excellent (kappa 0.82) to moderate (kappa 0.40-0.68). Sensitivity across assays ranged between 50.0% and 61.3%; specificity ranged between 68.6% and 100%. Comparisons of group 1 vs group 2 produced the greatest specificities, between 77.3% and 100%. In 17 cases that subsequently came to autopsy, 93% of SAAs were positive in those at the neocortical LBD stage but in only &lt;10% of those at lower stages. Skin biopsy α-synuclein SAA may be useful as a diagnostic and progression biomarker in Lewy body dementia clinical trials.

ABSTRACT Braak and others have proposed that Lewy body pathology (LBP) in Parkinson’s disease (PD) may arise not only in the brain but alternatively from an initial site in the gastrointestinal (GI) tract with subsequent passage to the central nervous system CNS through the vagus nerve or other routes. We tested this hypothesis by using both immunohistochemistry (IHC) and RT QuIC a form of alpha synuclein seed amplification assay (SAA) to detect alpha synuclein LBP in samples from selected brain regions and 10 GI tract sites taken from autopsies of 50 PD subjects and 128 elderly subjects without parkinsonism or dementia including 34 with IHC identified CNS incidental Lewy body disease (ILBD) and 94 with no Lewy body IHC pathology detected (NLB). A positive SAA or IHC result was restricted to the GI tract in only 2 subjects while LBP by either SAA or IHC was restricted to the brain in 11 subjects. To fairly compare GI-only with brain-only synucleinopathy, however, we would have to do SAA on brain samples from all ILBD and NLB cases in at least 4 critical brain regions: olfactory bulb, medulla, pons, and amygdala. Further SAA of brain regions is estimated, based on the proportional results to date, to potentially identify 21 additional brain-only LBP subjects, for a total of 32, if it were done on all of the NLB subjects. From this brain-only LBP is estimated to be 16 times more common than GI-only LBP. To assess the clinical impact of SAA-positive GI sites we found that the number of positive sites per subject is significantly correlated with UPDRS motor score and SCOPA-AUT GI related scores including those for salivation, straining, constipation, and bowel movement.

Parkinson’s disease (PD) significantly affects patients’ quality of life through debilitating motor symptoms, such as Freezing of Gait (FoG). Continuous, in-home monitoring of FoG is essential for timely clinical intervention but remains challenging due to high power consumption, annotation cost, and the controlled environments required by current wearables. We introduce LIFT-PD (the source code is available at: https://github.com/shovito66/LIFT-PD ), a novel self-supervised learning (SSL) framework for real-time, patient-independent FoG detection that uniquely utilizes a single waist-worn accelerometer—an approach traditionally considered less optimal due to weaker gait signatures. LIFT-PD leverages SSL on unlabeled data collected from uncontrolled, real-world settings and employs a novel Differential Hopping Windowing Technique (DHWT) to address gait variability and dataset imbalance. Additionally, an opportunistic inference module selectively activates the deep learning model only during patient movement, significantly reducing power consumption and enabling continuous monitoring ( \(>\) 48 hours). Experimental results show that LIFT-PD achieves a 7.25% increase in precision and 4.4% improvement in accuracy compared to supervised and semi-supervised baseline models while requiring approximately 40% fewer labeled training samples. Evaluations across diverse patient characteristics-including severity, medication state, age, and gender-confirm the model’s robustness and clinical applicability, positioning LIFT-PD as a practical, energy-efficient, and scalable solution for continuous real-world FoG monitoring in PD.

Background: Reoperative metabolic and bariatric surgery (MBS), consisting of revision and conversion surgery, carries higher morbidity and mortality compared with primary procedures, yet robust long-term data are limited. Methods: A retrospective review was conducted of all patients 18 years of age or older who underwent first-time reoperative MBS between 2000 and 2024 at a single large quaternary referral center. Data were stored securely and analyzed in R (v4.4.2) using standard descriptive statistics and group tests ( t tests/Wilcoxon/Kruskal-Wallis; χ²/Fisher). Sparse late-complication data precluded pairwise tests. Results: Three hundred sixty patients, 86% female, mean age 50 years, underwent reoperative MBS. Conversion to Roux-en-Y gastric bypass (49%) was the most common surgery. The majority were performed for weight recidivism (37%). Length of stay, estimated blood loss, length of surgery, complication rates, readmission rates, and reintervention rates varied by type of reoperative MBS performed and indication. Most early complications were Clavien-Dindo 2, and most late complications were Clavien-Dindo 3b for all approaches. There was one procedure-related death in the study following an open conversion. Conclusion: In this 24-year single-center cohort, weight recidivism was the most frequent indication for reoperation and was associated with improved perioperative outcomes and durable long-term weight loss. As the landscape of bariatric surgery continues to evolve, we recommend early referral to centers with reoperative MBS expertise.

Rationale: Neuromuscular blocking agents (NMBAs) show potential benefits on mortality and other complications of acute respiratory distress syndrome (ARDS) in adult patients. Evidence-based decisions and processes ensure appropriate use of neuromuscular blockade in adult patients with ARDS. Objectives: The objective of these guidelines was to develop evidence-based recommendations for the administration of NMBAs in critically ill adult patients with ARDS. Design: The American College of Critical Care Medicine Board convened a 21-member multidisciplinary panel of experts in critical care medicine, nursing, respiratory therapy, pharmacology, surgery, neurology, and anesthesiology. The panel included two expert methodologists specialized in developing evidence-based recommendations in alignment with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Conflict-of-interest policies were strictly followed during all phases of guidelines development including task force selection and voting. Methods: The panel members identified and formulated five Population, Intervention, Comparison, and Outcome questions. We conducted a systematic review for each question to identify the best available evidence, statistically analyzed the evidence, and assessed the certainty of the evidence using the GRADE methodology. We used the GRADE evidence-to-decision framework to formulate the recommendations. Results: The panel generated two conditional recommendations. One recommendation is to use NMBAs in adults with ARDS with Pa o 2 /F io 2 less than 150. For the other recommendations, there was equipoise in the recommendation for and against using titratable vs. fixed-dose NMBA dosing, a monitoring-based strategy for assessing depth of sedation and analgesia in adults with ARDS before initiating or while receiving neuromuscular blockade, and administration of NMBAs for patients who are proned, due to overall lack of evidence in critically ill patients and due to considerations of patient safety and experience concerns. Conclusions: These guidelines provide additional perspectives on the use of NMBA in patients with ARDS, recognizing that institutional and patient-specific considerations must help to guide the decision-making process.

The systemic impairment that accompanies liver cirrhosis is known to carry a significant burden on death and postoperative complications in cardiovascular interventions. This review analyzes the impact of liver cirrhosis on short‐ and long‐term outcomes after cardiac surgery and percutaneous procedures, providing an evidence‐based guidance in the decision‐making process and perioperative management of these patients. Several parameters should be considered by the heart teams when assessing eligibility, indications for intervention, and perioperative management of these patients. Life expectancy, long‐term procedural outcomes, Child–Pugh or the Model for End‐Stage Liver Disease score, presence of gastroesophageal varices and hepatic venous pressure gradient were extrapolated as the main determinants in decision making in patients with cirrhosis. Assessment and treatment of gastroesophageal varices is mandatory. Hepatic venous pressure gradient values >20 mm Hg preclude patients from a surgical approach. Considering the poor prognosis of advanced liver cirrhosis, futile treatments should be avoided. A multidimensional heart team approach involving surgical, cardiologic, anesthesiologic, hepatological, and medical considerations is recommended.