Citations

PURPOSE A multi-cancer detection test using a targeted methylation assay and machine learning classifiers was validated and optimized for screening in prospective, case-controlled Circulating Cell-free Genome Atlas (ClinicalTrials.gov identifier: NCT02889978 ) substudy 3. Here, we report test performance in a subgroup of participants with symptoms suspicious for cancer to assess the test's ability to potentially facilitate efficient diagnostic evaluation in symptomatic individuals. METHODS We evaluated test performance (sensitivity, specificity, and accuracy of cancer signal origin [CSO] prediction accuracy) in participants with clinically presenting cancers (CPCs) and noncancer with underlying medical conditions and among two subgroups (65 years and older and GI cancers). Overall survival (OS) of participants who had a cancer signal detected/not detected was compared with SEER-based expected survival. RESULTS A total of 2,036 cancer and 1,472 noncancer participants were included. Specificity was high in all noncancer participants (99.5% [95% CI, 98.4 to 99.8]). In participants with CPCs, the overall sensitivity was 64.3% (95% CI, 62.2 to 66.4) and the overall accuracy of CSO prediction in true positives was 90.3%. For GI cancers, the overall sensitivity was 84.1% (95% CI, 80.6 to 87.1). In participants 65 years and older, test performance was similar to that of all participants. Individuals with cancers not detected had a significantly better OS than that expected from SEER ( P < .01). CONCLUSION This test detected a cancer signal with high specificity and CSO prediction accuracy and moderate sensitivity in symptomatic individuals, with especially high performance in participants with GI cancers. The survival analysis implied that the cancers not detected were less clinically aggressive than cancers detected by the test, providing prognostic insights to physicians. This multi-cancer detection test could facilitate efficient workup and stratify cancer risk in symptomatic individuals.

Abstract INTRODUCTION We examined the progression of extrapyramidal symptoms and signs in autopsy‐confirmed dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD), and Alzheimer's disease dementia (AD). METHODS Longitudinal data were obtained from Arizona Study of Aging and Neurodegenerative Disease, with PDD ( n = 98), AD ( n = 47) and DLB ( n = 48) further sub‐grouped as with or without parkinsonism (DLB+ and DLB−). Within‐group Unified Parkinson's Disease Rating Scale (UPDRS) ‐II and UPDRS‐III trajectories were analyzed using non‐linear mixed effects models. RESULTS In DLB, 65.6% had parkinsonism. Baseline UPDRS‐II and III scores (off‐stage) were highest ( P < 0.001) for PDD (mean ± SD 14.3 ± 7.8 and 27.4 ± 16.3), followed by DLB+ (6.0 ± 8.8 and 17.2 ± 17.1), DLB− (1.1 ± 1.3 and 3.3 ± 5.5) and AD (3.2 ± 6.1 and 8.2 ± 13.6). Compared to PDD, the DLB+ group had faster UPDRS‐III progression over 8‐years (Cohen's‐ d range 0.98 to 2.79, P < 0.001), driven by gait ( P < 0.001) and limb bradykinesia ( P = 0.02) subscales. DISCUSSION Motor deficits progress faster in DLB+ than PDD, providing insights about expected changes in motor function. Highlights Dementia with Lewy bodies has faster motor progression than Parkinson's disease dementia Linear and non‐linear mixed modeling analysis of longitudinal data was utilized Findings have implications for clinical prognostication and trial design

Background: The authors examined whether ultrasound sensitivity, specificity, and accuracy in identifying intact repairs or flexor tendon gapping after zone 2 repair are affected by the number of suture strands crossing the repair or gap or imaging modality (static versus dynamic). Methods: A total of 144 fresh-frozen cadaveric digits (thumbs excluded) were randomized to either an intact repair (0-mm gap) or simulated failed repair (4-mm gap), as well as to either a two- or eight-strand locked-cruciate repair of a zone 2 flexor digitorum profundus tendon laceration using 4-0 Fiberwire. Examinations were performed by a blinded musculoskeletal ultrasonographer in static and dynamic modes using an 18-MHz transducer. Gaps were remeasured after scanning, and the final gap width recorded. McNemar exact test was used to determine whether there were differences in sensitivity, specificity, and accuracy affected by modality (static versus dynamic), and chi-square test was used to compare sensitivity, specificity, and accuracy between number of strands (two versus eight) crossing the intact repair or repair gap (≥4 mm). Results: Sensitivity, specificity, and accuracy improved with increased number of suture strands crossing the repair or gap (eight versus two), irrespective of modality (static versus dynamic), and dynamic compared with static scanning modes, irrespective of number of suture strands crossing the repair or gap site. Conclusions: The most sensitive and accurate means of assessing flexor tendon repair integrity and gapping were seen using the dynamic scanning mode. Increased number of suture strands did not negatively affect sensitivity, specificity, or accuracy, regardless of scanning mode (dynamic or static).

Abstract Objective Our objectives were to examine cross‐sectional correlations of headache disability with measures of resilience, anxiety, and depression, and to determine if resilience modified the association between headache severity/frequency and disability. Background Resilience is associated with quality of life and functioning among patients with chronic conditions. We investigated whether resilience strongly mitigates headache‐related disability as measured by the Migraine Disability Assessment (MIDAS). Methods We prospectively recruited 160 patients with primary headache disorders seen in a tertiary headache medicine program between February 20, 2018 and August 2, 2019. Each participant completed the MIDAS, Conner Davidson Resilience Scale (CDRS‐25), Patient Health Questionnaire‐9 (PHQ‐9), Generalized Anxiety Disorder‐7 (GAD‐7), and WHO‐5 Well‐Being Index. Results The CDRS‐25 score was negatively correlated with the total MIDAS ( r = −0.21, p = 0.009), GAD‐7 ( r = −0.56, p < 0.001), and PHQ‐9 scores ( r = −0.34, p < 0.001). Well‐being inversely correlated with disability ( r = −0.37, p < 0.001). Increases in anxiety and depression increased the odds of disability. A 1 point increase in the CDRS‐25 score decreased the odds of being severely disabled by 4% (OR = 0.96, 95% CI: 0.94 to 0.99, p = 0.001). However, the CDRS‐25 score did not significantly moderate the association between headache days and disability. Conclusion Traits associated with resilience decreased the odds of severe disability from headaches, whereas anxiety, depression, and headache frequency were strongly associated with higher disability from headache.

Abstract The objective of this study was to determine the prevalence, incidence, and clinical diagnostic accuracy for neuropathologically diagnosed progressive supranuclear palsy (PSP) with data from a longitudinal clinicopathological study using Rainwater criteria to define neuropathological PSP. Of 954 autopsy cases, 101 met Rainwater criteria for the neuropathologic diagnosis of PSP. Of these, 87 were termed clinicopathological PSP as they also had either dementia or parkinsonism or both. The prevalence of clinicopathologically defined PSP subjects in the entire autopsy dataset was 9.1%, while the incidence rate was estimated at 780 per 100 000 persons per year, roughly 50-fold greater than most previous clinically determined PSP incidence estimates. A clinical diagnosis of PSP was 99.6% specific but only 9.2% sensitive based on first examination, and 99.3% specific and 20.7% sensitive based on the final clinical exam. Of the clinicopathologically defined PSP cases, 35/87 (∼40%) had no form of parkinsonism at first assessment, while this decreased to 18/83 (21.7%) at final assessment. Our study confirms a high specificity but low sensitivity for the clinical diagnosis of PSP. The low clinical sensitivity for PSP is likely primarily responsible for previous underestimates of the PSP population incidence rate.

Background: Essential tremor (ET) is a common movement disorder in which cerebellar microscopic and volume alterations have been repeatedly reported although with disagreement between studies. However, pronounced heterogeneity was found with regard to cerebellar volume alterations. Objective: This study aimed to assess postmortem cerebellar volume in subjects with or without ET, as compared with subjects with multiple system atrophy (MSA), a well-established cerebellar neurodegeneration. Methods: Cases with ET ( n = 29), MSA ( n = 7), and non-demented control cases without any movement disorder ( n = 22) were selected from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND), a longitudinal clinicopathological study with annual research-dedicated clinical assessments by neuropsychologists, subspecialist movement disorders, and cognitive/behavioral neurologists, with comprehensive neuropathological examinations after death. Group comparisons were controlled for common age-related neurodegenerative and cerebrovascular pathologies. Cerebellar volumes were calculated using digital images of slices taken at the time of autopsy, immediately after brain removal and before fixation. Results: Cerebellar volume was not reduced in ET subjects compared to controls. The two groups did not differ in terms of incidental cerebrovascular and Alzheimer’s disease neuropathology. In contrast, cerebellar volume was significantly reduced in subjects with MSA when compared to ET and control subjects. Conclusion: In a well-characterized cohort, postmortem cerebellar volume measurements suggest that there are no volume alterations in ET when compared to controls, in contrast to significant cerebellar atrophy in subjects with MSA.

Introduction: Prehospital telestroke is increasingly utilized in mobile stroke units and telemedicine-enabled ambulances for acute ischemic stroke (AIS). While the NIHSS remains the standard for telestroke assessment, simpler scales have been validated to help paramedics recognize large vessel occlusion (LVO) strokes but have not been evaluated in a traditional telestroke network. We aimed to determine the accuracy of common LVO scales in a large academic telestroke practice. Methods: This retrospective study included all telestroke consults performed in a large academic telestroke network from 2019 to 2020. Patients were excluded if no NIHSS or vessel imaging was performed. We recorded presenting NIHSS, site of vessel occlusion, and discharge diagnosis. LVO was defined as an acute occlusion of the internal carotid artery and/or M1 middle cerebral artery. The NIHSS was used to calculate 7 LVO scales (RACE, C-STAT, FAST-ED, 3I-SS, PASS, VAN, and G-FAST). Diagnostic performance was assessed by calculating sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy using the established thresholds of each scale. These results were compared to NIHSS at thresholds of 6, 8, and 10. Area under curve (AUC) was calculated using c-statistics by treating scales as continuous variables. Results: A total of 625 patients were included, 373/625 (59.7%) of which were diagnosed with AIS at discharge. LVO was identified in 78/625 (12.5%) patients. VAN was the most sensitive prehospital stroke scale (83.3%), whereas 3I-SS ≥ 4 was the most specific (95.2%). Both the RACE and FAST-ED scales demonstrated superior accuracy and AUC compared to the NIHSS (Table 1). Conclusions: To our knowledge, this is the first study assessing LVO scale accuracy in a large telestroke network. As use of prehospital telestroke grows, this study highlights several scales that may allow for faster prehospital triage decisions without sacrificing accuracy.