Citations

Background and Aims: Among those with primary sclerosing cholangitis (PSC), perihilar cholangiocarcinoma (pCCA) is often diagnosed at a late stage and is a leading source of mortality. Detection of pCCA in PSC when curative action can be taken is challenging. Our aim was to create a deep learning model that analyzed MRI to detect early-stage pCCA and compare its diagnostic performance with expert radiologists. Approach and Results: We conducted a multicenter, international, retrospective cohort study involving adults with large duct PSC who underwent contrast-enhanced MRI. Senior abdominal radiologists reviewed the images. All patients with pCCA had early-stage cancer and were registered for liver transplantation. We trained a 3D DenseNet-121 model, a form of deep learning, using MRI images and assessed its performance in a separate test cohort. The study included 398 patients (training cohort n=150; test cohort n=248). pCCA was present in 230 individuals (training cohort n=64; test cohort n=166). In the test cohort, the respective performances of the model compared to the radiologists were: sensitivity 87.9% versus 50.0%, p <0.001; specificity 84.1% versus 100.0%, p <0.001; area under receiving operating curve 86.0% versus 75.0%, p <0.001. Even when a mass was absent, the model had a higher sensitivity for pCCA than radiologists (91.6% vs. 50.6%, p <0.001) and maintained good specificity (84.1%). Conclusions: The 3D DenseNet-121 MRI model effectively detects early-stage pCCA in PSC patients. Compared to expert radiologists, the model missed fewer cases of cancer.

Background Intolerance of Uncertainty (IU) has never been explored in functional motor disorder (FMD) or any functional neurological disorder but perceptions of control are theoretically relevant. Objective To evaluate if IU changes in people with FMD completing intensive 1-week motor retraining treatment, and if IU change associates with outcome. Methods A consecutive cohort of 45 FMD patients completed a 1-week intensive outpatient motor retraining treatment. At program beginning and end, patients self-rated IU using the Intolerance of Uncertainty Scale-12 (IUS-12) and four functional impairment measures. Paired t-tests analyzed program changes in IU and functional outcomes. Linear regressions analyzed association strength between IU change and outcome. Results IU improved with FMD treatment (p < 0.001). Pre- to post-treatment IU was improved in 32/45 (71%), stable in 5/45 (11%), and worsened in 8/45 (18%). Age, symptom duration, and FMD phenotype did not predict IU improvement. Self-rated function improved across measures with treatment (p < 0.001). Program change in IU positively predicted outcome on 3 of 4 measures. Conclusions IU improves with FMD rehabilitation, even without explicit psychological focus of treatment, regardless of age or FMD phenotype. Improving IU associates with positive FMD treatment outcomes suggesting an important treatment target in FMD.

Background: Many surgeons recommend weight loss for patients with obesity before total joint arthroplasty (TJA), but few studies have evaluated weight loss interventions. This study compared weight loss using a remote dietitian and a mobile application (app) with weight loss using standard care for patients with severe obesity before TJA. Methods: This multicenter randomized controlled trial included 60 subjects with a body mass index (BMI) of 40 to 47 kg/m 2 who had been scheduled for primary total hip or knee arthroplasty from September 2019 to January 2023. The mean age was 61 years, 67% were women, and the mean BMI was 44 kg/m 2 . The control subjects (n = 29) received standard care; the intervention subjects (n = 31) completed video calls with dietitians and used a mobile app for 12 weeks preoperatively. Weights and surveys were collected at baseline and 12 weeks, with 87% follow-up. Weight loss, patient-reported outcomes, complications, revisions, and reoperations were compared. The mean follow-up was 1.8 years. Results: The intervention subjects lost more weight (−4.1 versus −2.1 kg, p = 0.22) and had larger decreases in BMI (−1.4 versus −0.9 kg/m 2 , p = 0.36 than the controls, but not significantly so. The intervention subjects had higher odds of achieving a BMI of <40 kg/m 2 (odds ratio = 1.9, p = 0.44), but not significantly so. There were no significant differences in the mean change in the Hip disability and Osteoarthritis Outcome Score, the Knee injury and Osteoarthritis Outcome Score, or the Lower Extremity Activity Scale score. At baseline, only 11% had seen a dietitian in the last 3 months. Most subjects (83%) felt that video calls were helpful. There were no differences in complications between the groups; there was a patellar fracture in the control group and a deep venous thromboembolism in the intervention group. Conclusions: A preoperative weight loss intervention using a dietitian and a mobile app was feasible and viewed favorably among patients. Remote dietitians and mobile apps may address gaps in access to obesity treatment before TJA. While the intervention subjects lost more weight and were more likely to achieve a BMI of <40 kg/m 2 , the differences were not significant. More intensive interventions may be needed to achieve enough weight loss for clinically important improvements in TJA. Level of Evidence: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Understanding the imaging appearance of autoimmune disorders of the liver and biliary tract is important to guide further workup, suggest a particular diagnosis, monitor for disease progression or response to treatment, and evaluate for complications.

Background: Static ice storage (SIS) has long been accepted as the conventional lung preservation method, assuming to maintain 4 °C temperature. Although never directly confirmed by temperature measurements, this assumption has been widely accepted. We aimed to measure lung and preservation temperature with SIS in porcine experiments and clinical observations. Methods: Porcine lungs were preserved with SIS for 8 h (group I, n = 3) and 3 h followed by 10 °C storage (group II, n = 3). Tissue (tissueT°), first bag preservation solution (psT°) and second bag saline (salineT°) temperature were monitored. In clinical lungs (n = 4), psT° was monitored during SIS. Surface (surfaceT°) and core (coreT°) temperature were assessed before and after SIS (n = 62). Results: After 4 h in porcine lung group I, average tissueT° was 0.66 °C, psT° was 0.12 °C and salineT° was −0.02 °C. After 3 h in group II, average tissueT° was 1.90 °C, psT° was 0.57 °C and salineT° was 2.33 °C. In clinical observations, psT° was below 4 °C after 9–13 min and 0 °C after 78–267 min. After SIS, median surfaceT° was 1.25 °C (min-max; −3.2–9.2 °C) and coreT° was 1.45 °C (−0.4–4.8 °C). Conclusions: SIS leads to rapid temperature drops below 4 °C, approaching 0 °C within 2–4 h. The post-SIS lung temperature shows considerable variability and does not consistently remain at the commonly assumed 4 °C, posing potential freezing injury to donor lungs.

Abstract There are multiple underlying etiologies of patellar instability including both osseous and soft‐tissue factors. Obligate flexion dislocation consists of lateral dislocation of the patella, occurring each time the knee flexes. This generally results from a predominantly lateral contracture of the extensor mechanism and can be technically challenging to manage. Quadricepsplasty can be of particular clinical utility for obligate flexion dislocation and constitutes a realignment of the proximal soft‐tissue attachments of the patella. The described technique features isolation of the 4 muscles of the quadriceps and subsequent stepwise lengthening of the vastus lateralis, advancement of the vastus medialis obliquus, and Z‐lengthening of the rectus femoris and vastus intermedius. This technique can be used in isolation or in combination with other procedures, such as medial patellofemoral ligament reconstruction, to surgically address patellofemoral maltracking. Technique Video video See video under supplementary data.

Abstract Despite the availability of effective vaccines and a recent decrease in annual deaths, COVID-19 remains a leading cause of death. Serological studies provide insights into host immunobiology of adaptive immune response to infection, which holds promise for identifying high-risk individuals for adverse COVID-19 outcomes. We investigated correlates of anti-nucleocapsid antibody responses following SARS-CoV-2 infection in a US population-based meta-cohort of adults participating in longstanding National Institutes of Health–funded cohort studies. Anti-nucleocapsid antibodies were measured from dried blood spots collected between February 2021 and February 2023. Among 1419 Collaborative Cohort of Cohorts for COVID-19 Research participants with prior SARS-CoV-2 infection, the mean age (standard deviation) was 65.8 (12.1), 61% were women, and 42.8% self-reported membership in a race/ethnicity minority group. The proportion of participants reactive to nucleocapsid peaked at 69% by 4 months after infection and waned to only 44% ≥12 months after infection. Higher anti-nucleocapsid antibody response was associated with older age, Hispanic or American Indian Alaskan Native (vs White) race/ethnicity, lower income, lower education, former smoking, and higher anti-spike antibody levels. Asian race (vs White) and vaccination (even after infection) were associated with lower nucleocapsid reactivity. Neither vaccine manufacturer nor common cardiometabolic comorbidities were not associated with anti-nucleocapsid response. These findings inform the underlying immunobiology of adaptive immune response to infection, as well as the potential utility of anti-nucleocapsid antibody response for clinical practice and COVID-19 serosurveillance.

BACKGROUND: Spinal cord involvement is infrequently reported in primary central nervous system vasculitis (PCNSV). This study describes the clinical findings, therapeutic responses, and outcomes of spinal cord involvement in a large cohort of patients with PCNSV. METHODS: We retrospectively studied 216 consecutive patients with PCNSV evaluated at the Mayo Clinic from 1983 to 2023. Spinal cord involvement was documented by histological examination or imaging. The clinical, laboratory, radiological, and pathological findings, along with management and outcomes, were compared between patients with and without spinal cord involvement. RESULTS: Of 216 patients, 10 (4.6%) had spinal cord involvement, with cerebral involvement in 9 cases. One patient (0.5%) had isolated spinal cord vasculitis. Histological evidence of vasculitis was found in all 10, with necrotizing vasculitis in 5 (50%). Magnetic resonance imaging showed thoracic abnormalities in 8 patients, cervical spine involvement in 2, conus medullaris involvement in 3, and cauda equina enhancement in 4. Compared with the 206 patients without spinal cord involvement, those with spinal cord vasculitis were more likely to present with paraparesis/tetraparesis ( P <0.001) and necrotizing vasculitis ( P =0.01) and less likely with hemiparesis ( P =0.006) and granulomatous vasculitis ( P =0.03). Patients with spinal cord involvement were more likely to have at least 1 relapse ( P <0.001) or more ( P <0.001). No differences between the 2 groups were observed regarding long-term remission, therapy response, and high disability scores (modified Rankin Scale score, 4–6) or death at last follow-up. Spinal cord involvement was associated with meningeal enhancement on brain imaging (odds ratio, 10.50) and the presence of lymphoma (odds ratio, 6.49), specifically Hodgkin lymphoma diagnosed simultaneously with PCNSV. Spinal involvement was negatively associated with increasing age (odds ratio, 0.64) and cerebral infarction on imaging (odds ratio, 0.08). CONCLUSIONS: Spinal cord involvement defines a distinct subset of patients with PCNSV.

ABSTRACTObjectiveIntrathecal fluorescein (IF) is effective for localizing nasal cerebrospinal fluid (CSF) leaks along the skull base during endoscopic exploration, with largest studies reporting sensitivities ranging from 66%–93%. Due to reports of intraoperative and postoperative neurologic complications such as seizures and paralysis, surgeons often dilute the fluorescein and inject it intrathecally slowly over a variable amount of time. However, no study has assessed whether rapid IF administration causes the aforementioned risks or whether it affects its accuracy in identifying CSF leaks intraoperatively.MethodsA prospective study was conducted from 2015 to 2024, where all patients undergoing endoscopic exploration and/or repair of CSF rhinorrhea had 0.1 mL of 10% fluorescein (10 mg) mixed with 3–5 mL of patients' CSF injected rapidly via the lumbar drain over a few seconds.ResultsOf the 82 included patients, the mean age was 53.8 ± 15.2 years, and 84% were female. Sixty‐nine patients underwent successful endoscopic CSF leak repairs, and 13 had negative endoscopic explorations. Rapid IF injection was 80% sensitive (20% false negative rate) and 100% specific for identifying CSF leaks, and it caused no seizures, paralysis, or other neurologic complications.ConclusionCompared to prior reports of slow low‐dose IF injection for CSF leak localization, rapid IF injection yielded similar efficacy (80% sensitivity) with no IF‐related complications. Rapid IF injection was safe and effective but should be corroborated by future studies.Level of Evidence4.

Thrombospondin-2 (THBS2) is a prevailing prognostic biomarker implicated in different cancer types, such as deadly colorectal, pancreas, and triple-negative breast cancers. While the current methods for cancer-relevant protein detection, such as enzyme-linked immunosorbent assay (ELISA), mass spectrometry, and immunohistochemistry, are feasible at advanced stages, they have shortcomings in sensitivity, specificity, and accessibility, particularly at low concentrations in complex biological fluids for early detection. Here, we propose and demonstrate a modular, in-solution assay design concept, Nanoparticle-Supported Rapid Electronic Detection (NasRED), as a versatile cancer screening and diagnostic platform. NasRED utilizes antibody-functionalized gold nanoparticles (AuNPs) to capture target proteins from a minute amount of sample (<10 µL) and achieve optimal performance with a short assay time by introducing active fluidic forces that act to promote biochemical reaction and accelerate signal transduction. This rapid (15 min) process serves to form AuNP clusters upon THBS2 binding and subsequently precipitate such clusters, resulting in color modulation of the test tubes that is dependent on the THBS2 concentration. Finally, a semiconductor-based, portable electronic device is used to digitize the optical signals for the sensitive detection of THBS2. High sensitivity (femtomolar level) and a large dynamic range (five orders of magnitude) are obtained to analyze THBS2 spiked in PBS, serum, whole blood, saliva, cerebrospinal fluids, and synovial fluids. High specificity is also preserved in differentiating THBS2 from other markers such as cancer antigen (CA) 19-9 and bovine serum albumin (BSA). This study highlights NasRED’s potential to enhance cancer prognosis and screening by offering a cost-effective, accessible, and minimally invasive solution.