Citations

Abstract Background White matter hyperintensities (WMH) are considered hallmark features of cerebral small vessel disease and have recently been linked to Alzheimer’s disease pathology. Their distinct spatial distributions, namely periventricular versus deep WMH, may differ by underlying age-related and pathobiological processes contributing to cognitive decline. We aimed to identify the spatial patterns of WMH using the 4-scale Fazekas visual assessment and explore their differential association with age, vascular health, Alzheimer’s imaging markers, namely amyloid and tau burden, and cognition. Because our study consisted of scans from GE and Siemens scanners with different resolutions, we also investigated inter-scanner reproducibility and combinability of WMH measurements on imaging. Methods We identified 1144 participants from the Mayo Clinic Study of Aging consisting of older adults from Olmsted County, Minnesota with available structural magnetic resonance imaging (MRI), amyloid, and tau positron emission tomography (PET). WMH distribution patterns were assessed on FLAIR-MRI, both 2D axial and 3D, using Fazekas ratings of periventricular and deep WMH severity. We compared the association of periventricular and deep WMH scales with vascular risk factors, amyloid-PET and tau-PET standardized uptake value ratio, WMH volume, and cognition using Pearson partial correlation after adjusting for age. We also evaluated vendor compatibility and reproducibility of the Fazekas scales using intraclass correlations (ICC). Results Periventricular and deep WMH measurements showed similar correlations with age, cardiometabolic conditions score (vascular risk), and cognition, (p < 0.001). Both periventricular WMH and deep WMH showed weak associations with amyloidosis (R = 0.07, p = < 0.001), and none with tau burden. We found substantial agreement between data from the two scanners for Fazekas measurements (ICC = 0.78). The automated WMH volume had high discriminating power for identifying participants with Fazekas ≥ 2 (area under curve = 0.97). Conclusion Our study investigates risk factors underlying WMH spatial patterns and their impact on global cognition, with no discernible differences between periventricular and deep WMH. We observed minimal impact of amyloidosis on WMH severity. These findings, coupled with enhanced inter-scanner reproducibility of WMH data, suggest the combinability of inter-scanner data assessed by harmonized protocols in the context of vascular contributions to cognitive impairment and dementia biomarker research.

ImportanceRedirection of care refers to withdrawal, withholding, or limiting escalation of treatment. Whether maternal social determinants of health are associated with redirection of care discussions merits understanding.ObjectiveTo examine associations between maternal social determinants of health and redirection of care discussions for infants born extremely preterm.Design, Setting, and ParticipantsThis is a retrospective analysis of a prospective cohort of infants born at less than 29 weeks’ gestation between April 2011 and December 2020 at 19 National Institute of Child Health and Human Development Neonatal Research Network centers in the US. Follow-up occurred between January 2013 and October 2023. Included infants received active treatment at birth and had mothers who identified as Black or White. Race was limited to Black and White based on service disparities between these groups and limited sample size for other races. Maternal social determinant of health exposures were education level (high school nongraduate or graduate), insurance type (public/none or private), race (Black or White), and ethnicity (Hispanic or non-Hispanic).Main Outcomes and MeasuresThe primary outcome was documented discussion about redirection of infant care. Secondary outcomes included subsequent redirection of care occurrence and, for those born at less than 27 weeks’ gestation, death and neurodevelopmental impairment at 22 to 26 months’ corrected age.ResultsOf the 15 629 infants (mean [SD] gestational age, 26 [2] weeks; 7961 [51%] male) from 13 643 mothers, 2324 (15%) had documented redirection of care discussions. In unadjusted comparisons, there was no significant difference in the percentage of infants with redirection of care discussions by race (Black, 1004/6793 [15%]; White, 1320/8836 [15%]) or ethnicity (Hispanic, 291/2105 [14%]; non-Hispanic, 2020/13 408 [15%]). However, after controlling for maternal and neonatal factors, infants whose mothers identified as Black or as Hispanic were less likely to have documented redirection of care discussions than infants whose mothers identified as White (Black vs White adjusted odds ratio [aOR], 0.84; 95% CI, 0.75-0.96) or as non-Hispanic (Hispanic vs non-Hispanic aOR, 0.72; 95% CI, 0.60-0.87). Redirection of care discussion occurrence did not differ by maternal education level or insurance type.Conclusions and RelevanceFor infants born extremely preterm, redirection of care discussions occurred less often for Black and Hispanic infants than for White and non-Hispanic infants. It is important to explore the possible reasons underlying these differences.

Objective The aims of this study were to assess whether a relationship between anti–SSA-52 and interstitial lung disease (ILD) can be further defined, and to enhance screening, detection, and potentially guide treatment. Methods A historical cohort study of 201 patients was conducted at a single tertiary care center between January 1, 2016 and December 31, 2020. All included patients were anti–SSA-52 antibody positive. Chart review was performed for laboratory values, symptoms, pulmonary function tests, treatment, and imaging. Chest computed tomographies were reviewed by chest radiologists. Results Among anti–SSA-52 antibody–positive patients, ILD was found in 125 (62.2%) compared with 76 (37.8%) with no ILD (p = 0.001). For those with ILD, 78 (62.4%) were diagnosed with connective tissue disease (CTD)–associated ILD, 28 (22.4%) were diagnosed ILD only, and 19 (15.2%) met the criteria for interstitial pneumonia with autoimmune features. In patients with CTD-ILD, 18 (23.0%) had their ILD diagnosis made over 6 months before a CTD diagnosis, and an additional 43 (55.1%) had their ILD and CTD diagnosed within 6 months of each other (p < 0.001). Common computed tomography patterns were nonspecific interstitial pneumonia/organizing pneumonia overlap in 44 (35.2%), 25 (20.0%) nonspecific interstitial pneumonia, and 15 (12%) usual interstitial pneumonia. Twenty-eight (35.9%) had antisynthetase syndrome, followed by 16 (20.5%) with dermatomyositis, 10 (12.8%) with CTD overlap, and 6 (7.7%) with systemic scleroderma. Conclusions There was a significant association between anti–SSA-52 antibodies and ILD across a wide spectrum of rheumatological diagnoses. A significant portion of patients were diagnosed with ILD either at the same time or before their CTD diagnosis. Further study will be needed to assess effective treatment and response.

Summary Background Stricturing Crohn's disease (CD) occurs most commonly in the terminal ileum and poses a clinical problem. Cross‐sectional imaging modalities such as intestinal ultrasound (IUS), computed tomography enterography (CTE), and magnetic resonance enterography (MRE) allow for assessment of the entire bowel wall and associated peri‐enteric findings. Radiologic definitions of strictures have been developed for CTE and MRE; their reliability and responsiveness are being evaluated in index development programs. A comprehensive assessment strategy for strictures using IUS is needed. Aims To provide a detailed summary of definitions, diagnosis and monitoring of strictures on IUS as well as technical aspects of image acquisition. Methods We searched four databases up to 6 January 2024. Two‐stage screening was done in duplicate. We assessed risk of bias using QUADAS‐2. Results There were 56 studies eligible for inclusion. Definitions for strictures on IUS are heterogeneous, but the overall accuracy for diagnosis of strictures is high. The capability of IUS for characterising inflammation versus fibrosis in strictures is not accurate enough to be used in clinical practice or trials. We summarise definitions for improvement of strictures on IUS, and discuss parameters for image acquisition and standardisation. Conclusions This systematic review is the first step for a structured program to develop a stricture IUS index for CD.

Abstract Purpose The purpose of this white paper is to educate health care professionals about the evolution of telemedicine (TM) and to propose a hybrid model that leverages the strengths of traditional in-person medicine as well as virtual medicine while maximizing the safety and quality of men’s sexual health care. Literature Search Strategy A literature search focused on the use of TM in urology and men’s health was performed through PubMed/MEDLINE, Embase, and Web of Science (January 1, 2012–April 26, 2022). Keywords included all known permutations of the terminology used to refer to virtual health, care as well as the terminology used to refer to urologic diseases, issues specific to men’s health, and men’s sexual health concerns. Publications that emerged after the literature search that met this criterion also were incorporated. Opinion pieces, letters to the editor, meeting abstracts, and conference proceedings were excluded. Additional resources were retrieved, such as governmental technical reports, legislative updates and reviews, and blogs. This search strategy yielded 1684 records across databases after removal of duplicates. Abstracts from the retrieved records were reviewed for relevance. Relevant publications were defined as those that reported data on any aspect of TM use specific to urology, men’s health, and/or men’s sexual health. If relevance was unclear from the abstract, then the full text of the article was retrieved for a more detailed review. In addition, the published evidence-based practice guidelines relevant to care for erectile dysfunction, Peyronie’s disease, ejaculatory dysfunction, and hypogonadism were retrieved. The most common reasons for article exclusions were a focus on TM use in disciplines other than urology and the absence of data (ie, opinion pieces). After exclusions, a total of 91 publications remained and constituted the evidence base for this paper.

AimsModular dual-mobility (DM) articulations are increasingly used during total hip arthroplasty (THA). However, concerns remain regarding the metal liner modularity. This study aims to correlate metal artifact reduction sequence (MARS)-MRI abnormalities with serum metal ion levels in patients with DM articulations.MethodsA total of 45 patients (50 hips) with a modular DM articulation were included with mean follow-up of 3.7 years (SD 1.2). Enrolled patients with an asymptomatic, primary THA and DM articulation with over two years’ follow-up underwent MARS-MRI. Each patient had serum cobalt, chromium, and titanium levels drawn. Patient satisfaction, Oxford Hip Score, and Forgotten Joint Score-12 (FJS-12) were collected. Each MARS-MRI was independently reviewed by fellowship-trained musculoskeletal radiologists blinded to serum ion levels.ResultsOverall, two patients (4.4%) had abnormal periprosthetic fluid collections on MARS-MRI with cobalt levels > 3.0 μg/l. Four patients (8.9%) had MARS-MRI findings consistent with greater trochanteric bursitis, all with cobalt levels < 1.0 μg/l. A seventh patient had a periprosthetic fluid collection with normal ion levels. Of the 38 patients without MARS-MRI abnormalities, 37 (97.4%) had cobalt levels < 1.0 μg/l, while one (2.6%) had a cobalt level of 1.4 μg/l. One patient (2.2%) had a chromium level > 3.0 μg/l and a periprosthetic fluid collection. Of the 41 patients with titanium levels, five (12.2%) had titanium levels > 5.0 μg/l without associated MARS-MRI abnormalities.ConclusionPeriprosthetic fluid collections associated with elevated serum cobalt levels in patients with asymptomatic DM articulations occur infrequently (4.4%), but further assessment is necessary due to implant heterogeneity.Cite this article: Bone Joint J 2024;106-B(3 Supple A):89–96.

Background and Aims: Despite the substantial impact of environmental factors, individuals with a family history of liver cancer have an increased risk for HCC. However, genetic factors have not been studied systematically by genome-wide approaches in large numbers of individuals from European descent populations (EDP). Approach and Results: We conducted a 2-stage genome-wide association study (GWAS) on HCC not affected by HBV infections. A total of 1872 HCC cases and 2907 controls were included in the discovery stage, and 1200 HCC cases and 1832 controls in the validation. We analyzed the discovery and validation samples separately and then conducted a meta-analysis. All analyses were conducted in the presence and absence of HCV. The liability-scale heritability was 24.4% for overall HCC. Five regions with significant ORs (95% CI) were identified for nonviral HCC: 3p22.1, MOBP, rs9842969, (0.51, [0.40–0.65]); 5p15.33, TERT, rs2242652, (0.70, (0.62–0.79]); 19q13.11, TM6SF2, rs58542926, (1.49, [1.29–1.72]); 19p13.11 MAU2, rs58489806, (1.53, (1.33–1.75]); and 22q13.31, PNPLA3, rs738409, (1.66, [1.51–1.83]). One region was identified for HCV-induced HCC: 6p21.31, human leukocyte antigen DQ beta 1, rs9275224, (0.79, [0.74–0.84]). A combination of homozygous variants of PNPLA3 and TERT showing a 6.5-fold higher risk for nonviral-related HCC compared to individuals lacking these genotypes. This observation suggests that gene-gene interactions may identify individuals at elevated risk for developing HCC. Conclusions: Our GWAS highlights novel genetic susceptibility of nonviral HCC among European descent populations from North America with substantial heritability. Selected genetic influences were observed for HCV-positive HCC. Our findings indicate the importance of genetic susceptibility to HCC development.

Neurovascular coupling (NVC) is the mechanism that drives the neurovascular response to neural activation, and NVC dysfunction has been implicated in various neurologic diseases. NVC is driven by (1) nonmetabolic feedforward mechanisms that are mediated by various signaling pathways and (2) metabolic feedback mechanisms that involve metabolic factors. However, the interplay between these feedback and feedforward mechanisms remains unresolved. We propose that feedforward mechanisms normally drive a swift, neural activation–induced regional cerebral blood flow (rCBF) overshoot, which floods the tissue beds, leading to local hypocapnia and hyperoxia. The feedback mechanisms are triggered by the resultant hypocapnia (not hyperoxia), which causes cerebral vasoconstriction in the neurovascular unit that counterbalances the rCBF overshoot and returns rCBF to a level that matches the metabolic activity. If feedforward mechanisms function improperly (eg, in a disease state), the rCBF overshoot, tissue-bed flooding, and local hypocapnia fail to occur or occur on a smaller scale. Consequently, the neural activation–related increase in metabolic activity results in local hypercapnia and hypoxia, both of which drive cerebral vasodilation and increase rCBF. Thus, feedback mechanisms ensure the brain milieu’s stability when feedforward mechanisms are impaired. Our proposal integrates the feedforward and feedback mechanisms underlying NVC and suggests that these 2 mechanisms work like a fail-safe system, to a certain degree. We also discussed the difference between NVC and cerebral metabolic rate-CBF coupling and the clinical implications of our proposed framework.