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There are four solid tumors with common screening options in the average-risk population aged 21 to 75 years (breast, cervical, colorectal, and, based on personalized risk assessment, prostate), but many cancers lack recommended population screening and are often detected at advanced stages when mortality is high. Blood-based multi-cancer early detection tests have the potential to improve cancer mortality through additional population screening. Reported here is a post-hoc analysis from the third Circulating Cell-free Genome Atlas substudy to examine multi-cancer early detection test performance in solid tumors with and without population screening recommendations and in hematologic malignancies. Participants with cancer in the third Circulating Cell-free Genome Atlas substudy analysis were split into three subgroups: solid screened tumors (breast, cervical, colorectal, prostate), solid unscreened tumors, and hematologic malignancies. In this post hoc analysis, sensitivity is reported for each subgroup across all ages and those aged ⩾50 years overall, by cancer, and by clinical cancer stage. Aggregate sensitivity in the solid screened, solid unscreened, and hematologic malignancy subgroups was 34%, 66%, and 55% across all cancer stages, respectively; restricting to participants aged ⩾50 years showed similar aggregate sensitivity. Aggregate sensitivity was 27%, 53%, and 60% across stages I to III, respectively. Within the solid unscreened subgroup, aggregate sensitivity was >75% in 8/18 cancers (44%) and >50% in 13/18 (72%). This multi-cancer early detection test detected cancer signals at high (>75%) sensitivity for multiple cancers without existing population screening recommendations, suggesting its potential to complement recommended screening programs. Clinical trial identifier: NCT02889978.

(1) Background: Cabozantinib, a multikinase inhibitor, is approved by the Food and Drug Administration (FDA) for the treatment of advanced hepatocellular carcinoma (HCC) following progression on sorafenib. Recently, atezolizumab plus bevacizumab has been approved in the first line setting for advanced HCC and has become the new standard of care. Whether cabozantinib improves outcomes following progression on immunotherapy remains unknown. We describe the clinical outcomes following treatment with immunotherapy in patients with advanced HCC who received cabozantinib. (2) Methods: We conducted a multicentric, retrospective analysis of patients with advanced HCC diagnosed between 2010–2021 at Mayo Clinic in Minnesota, Arizona, and Florida who received cabozantinib. Median overall survival and progression free survival analyses were performed using the Kaplan–Meier method. Adverse events were determined using Common Terminology Criteria for Adverse Events (CTCAE). (3). Results: We identified 26 patients with advanced HCC who received cabozantinib following progression on immunotherapy. Median progression free survival on cabozantinib therapy was 2.1 months (95% CI: 1.3–3.9) and median overall survival from time of cabozantinib initiation was 7.7 months (95% CI: 5.3–14.9). (4) Conclusion: The optimal sequencing of therapy for patients with advanced HCC following progression on immunotherapy remains unknown. Our study demonstrates that patients may benefit from treatment with cabozantinib following progression on immunotherapy.

Abstract Study Objectives Isolated REM sleep behavior disorder (iRBD) carries a high lifetime risk for phenoconversion to a defined neurodegenerative disease (NDD) including Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. We aimed to examine iRBD patient values and preferences regarding prognostic counseling. Methods One hundred thirteen iRBD patient participants enrolled in the Mayo Clinic iRBD Patient Registry were sent an email survey concerning their values and preferences concerning NDD prognostic counseling and their experiences following diagnosis with iRBD. Results Of 81 respondents (71.7% response rate), the majority were men (74.0%) with an average age of 65.7 (±9.7) years. Responses indicated a strong preference toward receiving prognostic information about possible future NDD development. 92.5% of respondents felt knowledge concerning personal NDD risk was important, while 87.6% indicated prognostic discussions were important to maintaining trust in their physician. 95.7% indicated a desire for more information, while only 4.3% desired less information regarding their NDD prognostic risk. Most respondents strongly agreed that prognostic information was important to discuss with their family and friends and inform future life planning, and most expressed interest in learning more about future neuroprotective therapies and symptomatic treatments for parkinsonism and dementia. Conclusions Most iRBD patients indicated strong preferences for disclosure of NDD prognostic risk and indicated that prognostic information was important for family discussions and future life planning. Future broader surveys and qualitative studies of clinic-based and ultimately community dwelling iRBD patients’ values and preferences are needed to guide appropriately tailored and individualized prognostic counseling approaches following iRBD diagnosis.

BACKGROUND: The lingual process of the sphenoid bone (LP) and the petrolingual ligament (PLL) surround laterally the internal carotid artery within the middle cranial fossa (MCF). OBJECTIVE: To study the LP and the PLL and anatomical variations considering their relationships with different structures and landmarks within the MCF, especially oriented toward the endoscopic endonasal approaches. METHODS: Seventy-two sides of dry skulls and 20 sides of embalmed specimens were studied. The measurements of the LP and the PLL were obtained, considering important landmarks in the MCF. RESULTS: The LP had a mean length and height of 5 mm and 3 mm, respectively. Its distance from the foramen lacerum was 6 mm, from the foramen ovale 10 mm, foramen rotundum 15 mm, and petrous apex 9 mm. In 44 sides (61.11%), the LP partially closed the lateral aspect of the carotid sulcus; in 17 sides (23.61%), it was found as a near-ring; and in 11 sides (15.2%), it was considered rudimentary. Considering the PLL, its length and height were, respectively, 9 mm, and 4 mm. CONCLUSION: The LP and PLL separate the carotid artery at the inferior aspect of Meckel's cave and constitute important landmarks for endoscopic endonasal approaches to Meckel's cave and MCF, and their identification and removal is essential for internal carotid artery mobilization in this area.

Background and Aims: This study aimed to investigate safety and efficacy of silmitasertib, an oral small molecule casein kinase 2 inhibitor, plus gemcitabine and cisplatin (G+C) versus G+C in locally advanced/metastatic cholangiocarcinoma. Approach and Results: This work is a Phase 1b/2 study (S4‐13‐001). In Phase 2, patients received silmitasertib 1000 mg twice daily for 10 days with G+C on Days 1 and 8 of a 21‐day cycle. Primary efficacy endpoint was progression‐free survival (PFS) in the modified intent‐to‐treat population (defined as patients who completed at least one cycle of silmitasertib without dose interruption/reduction) from both phases (silmitasertib/G+C n = 55, G+C n = 29). The response was assessed by Response Evaluation Criteria in Solid Tumors v1.1. The median PFS was 11.2 months (95% confidence interval [CI], 7.6, 14.7) versus 5.8 months (95% CI, 3.1, not evaluable [NE]) ( p = 0.0496); 10‐month PFS was 56.1% (95% CI, 38.8%, 70.2%) versus 22.2% (95% CI, 1.8%, 56.7%); and median overall survival was 17.4 months (95% CI, 13.4, 25.7) versus 14.9 months (95% CI, 9.9, NE) with silmitasertib/G+C versus G+C. Overall response rate was 34.0% versus 30.8%; the disease control rate was 86.0% versus 88.5% with silmitasertib/G+C versus G+C. Almost all silmitasertib/G+C (99%) and G+C (93%) patients reported at least one treatment emergent adverse event (TEAE). The most common TEAEs (all grades) with silmitasertib/G+C versus G+C were diarrhea (70% versus 13%), nausea (59% vs. 30%), fatigue (47% vs. 47%), vomiting (39% vs. 7%), and anemia (39% vs. 30%). Twelve patients (10%) discontinued treatment because of TEAEs during the study. Conclusions: Silmitasertib/G+C demonstrated promising preliminary evidence of efficacy for the first‐line treatment of patients with locally advanced/metastatic cholangiocarcinoma.

AbstractBackground and ObjectivesSubstance use disorders (SUDs) are chronic relapsing diseases characterized by significant morbidity and mortality. Phenomenologically, patients with SUDs present with a repeating cycle of intoxication, withdrawal, and craving, significantly impacting their diagnosis and treatment. There is a need for better identification and monitoring of these disease states. Remote monitoring chronic illness with wearable devices offers a passive, unobtrusive, constant physiological data assessment. We evaluate the current evidence base for remote monitoring of nonalcohol, nonnicotine SUDs.MethodsWe performed a systematic, comprehensive literature review and screened 1942 papers.ResultsWe found 15 studies that focused mainly on the intoxication stage of SUD. These studies used wearable sensors measuring several physiological parameters (ECG, HR, O2, Accelerometer, EDA, temperature) and implemented study‐specific algorithms to evaluate the data.Discussion and ConclusionsStudies were extracted, organized, and analyzed based on the three SUD disease states. The sample sizes were relatively small, focused primarily on the intoxication stage, had low monitoring compliance, and required significant computational power preventing “real‐time” results. Cardiovascular data was the most consistently valuable data in the predictive algorithms. This review demonstrates that there is currently insufficient evidence to support remote monitoring of SUDs through wearable devices.Scientific SignificanceThis is the first systematic review to show the available data on wearable remote monitoring of SUD symptoms in each stage of the disease cycle. This clinically relevant approach demonstrates what we know and do not know about the remote monitoring of SUDs within disease states.

ImportanceThere was a shift in patient volume from in-person to video telemedicine visits during the COVID-19 pandemic.ObjectiveTo determine the concordance of provisional diagnoses established at a video telemedicine visit with diagnoses established at an in-person visit for patients presenting with a new clinical problem.Design, Setting, and ParticipantsThis is a diagnostic study of patients who underwent a video telemedicine consultation followed by an in-person outpatient visit for the same clinical problem in the same specialty within a 90-day window. The provisional diagnosis made during the video telemedicine visit was compared with the reference standard diagnosis by 2 blinded, independent medical reviewers. A multivariate logistic regression model was used to determine factors significantly related to diagnostic concordance. The study was conducted at a large academic integrated multispecialty health care institution (Mayo Clinic locations in Rochester, Minnesota; Scottsdale and Phoenix, Arizona; and Jacksonville, Florida; and Mayo Clinic Health System locations in Iowa, Wisconsin, and Minnesota) between March 24 and June 24, 2020. Participants included Mayo Clinic patients residing in the US without age restriction. Data analysis was performed from December 2020 to June 2021.ExposuresNew clinical problem assessed via video telemedicine visit to home using Zoom Care Anyplace integrated into Epic.Main Outcomes and MeasuresConcordance of provisional diagnoses established over video telemedicine visits compared against a reference standard diagnosis.ResultsThere were 2393 participants in the analysis. The median (IQR) age of patients was 53 (37-64) years; 1381 (57.7%) identified as female, and 1012 (42.3%) identified as male. Overall, the provisional diagnosis established over video telemedicine visit was concordant with the in-person reference standard diagnosis in 2080 of 2393 cases (86.9%; 95% CI, 85.6%-88.3%). Diagnostic concordance by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision chapter ranged from 64.7% (95% CI, 42.0%-87.4%) for diseases of the ear and mastoid process to 96.8% (95% CI, 94.7%-98.8%) for neoplasms. Diagnostic concordance by medical specialty ranged from 77.3% (95% CI, 64.9%-89.7%) for otorhinolaryngology to 96.0% (92.1%-99.8%) for psychiatry. Specialty care was found to be significantly more likely than primary care to result in video telemedicine diagnoses concordant with a subsequent in-person visit (odds ratio, 1.69; 95% CI, 1.24-2.30; P < .001).Conclusions and RelevanceThis diagnostic study of video telemedicine visits yielded a high degree of diagnostic concordance compared with in-person visits for most new clinical concerns. Some specific clinical circumstances over video telemedicine were associated with a lower diagnostic concordance, and these patients may benefit from timely in-person follow-up.

INTRODUCTION: We recently developed a fluorescence in situ hybridization probe set for evaluating suspicious biliary and pancreatic duct strictures (PB-FISH). We aimed to determine whether PB-FISH results in biliary brush cytology specimens are associated with outcomes of patients with cholangiocarcinoma (CCA). METHODS: We performed a retrospective study of patients with CCA tested by PB-FISH from January 2015 to August 2018. CCA was stratified by primary sclerosing cholangitis (PSC) into those with (PSC CCA) or without PSC ( de novo CCA). PB-FISH results were categorized as polysomy (gain of multiple loci), nonpolysomy (single locus gain, single locus gain with 9p21 loss, homozygous 9p21 loss, tetrasomy), and disomy (no abnormalities). Overall survival (OS) was estimated using Kaplan-Meier methods and compared between the PB-FISH results using log-rank tests. Cox models were adjusted for age, sex, CA 19-9, cytology results, source of brushing sample, and treatments. RESULTS: Characteristics of 264 eligible patients (median age 60.4; range 18–92) were comparable for patients with PB-FISH polysomy vs nonpolysomy vs disomy. The median OS was similar between disomy, nonpolysomy, and polysomy in the overall population (22.7 vs 22.7 vs 20.3 months, respectively). For de novo CCA, both polysomy and nonpolysomy were associated with worse OS compared with disomy (polysomy: hazard ratio [HR] = 2.09, 95% confidence interval [CI] = 1.14–3.83; nonpolysomy: HR = 2.4, 95% CI = 0.54–2.46; P = 0.027). For PSC CCA, neither polysomy nor nonpolysomy were significantly associated with worse OS (polysomy: 0.90, 95% CI = 0.47–1.75; nonpolysomy: HR = 1.78, CI = 0.71–4.49; P = 0.27). DISCUSSION: PB-FISH alterations are associated with worse survival in de novo CCA, though statistical significance was lost when adjusting for confounding variables.