Changes in fasting plasma glucose and subclinical atherosclerosis: A cohort study from VIPVIZA trial.

BACKGROUND AND AIMS: Studies on the influence of fasting plasma glucose (FPG) on the development of carotid plaque (CP) and intima media thickness (CIMT) mainly focused on single FPG measures. We investigated whether changes in FPG (ΔFPG) are associated with incident CP and CIMT change (ΔCIMT) over time. METHODS: Analyses were based on information from 1896 participants from the VIPVIZA trial (Visualization of asymptomatic atherosclerotic disease for optimum cardiovascular prevention), with baseline and 3-year follow-up data on FPG, ultrasonographic CP (none or ≥1 lesion/s) and CIMT assessments. We studied the association between baseline FPG (prior to intervention) or 3-year ΔFPG (mmol/L) and incident CP (logistic regression) or ΔCIMT (linear regression). Analyses were adjusted for multiple potential confounders. RESULTS: 1896 and 873 individuals, respectively, were included in the analysis on incident CP and ΔCIMT. Participants were 60 years old at baseline and 61% and 54% were females, in the CP and CIMT analyses, respectively. Every mmol/L increase in FPG was associated with an increased odds of incident CP (odds ratio: 1.42, 95% confidence interval [CI]: 1.17, 1.73), but there was no association with ΔCIMT (mean difference: 0.002 mm, 95% CI: -0.003, 0.008) after 3 years. Baseline FPG was not associated with incident CP nor ΔCIMT progression. CONCLUSIONS: In middle-aged individuals with low to moderate risk for cardiovascular diseases, 3-year ΔFPG was positively associated with the risk of incident CP, but not with ΔCIMT. Single measures of FPG may not be sufficient in estimating cardiovascular risk among individuals with low to moderate risk.

Machine Learning in Antibody Diagnostics for Inflammatory Bowel Disease Subtype Classification.

Antibody testing in inflammatory bowel disease (IBD) can add to diagnostic accuracy of the main subtypes Crohn's disease (CD) and ulcerative colitis (UC). Whether modern modeling techniques such as supervised and unsupervised machine learning are of value for finer distinction of subtypes such as IBD-unclassified (IBD-U) is not known. We determined the antibody profile of 100 adult IBD patients from the Swiss IBD cohort study with known subtype (50 CD, 50 UC) as well as of 76 IBD-U patients. We included ASCA IgG and IgA, p-ANCA, MPO- and PR3-ANCA, and xANCA measurements for computing different antibody panels as well as machine learning models. The AUC of an optimized antibody panel was 85% (95%CI, 78-92%) to distinguish CD from UC patients. The antibody profile of IBD-U patients was closely related to UC. No specific antibody profile was predictive for IBD-U nor for re-classification. The panel diagnostic was in favor of UC reclassification prediction with a correct assignment rate of 69.2-73.1% depending on the cut-off applied. Supervised machine learning could not distinguish between CD, UC, and IBD-U. More so, unsupervised machine learning suggested only two distinct clusters as a likely number of IBD subtypes. Antibodies in IBD are supportive in confirming clinical determined subtypes CD and UC but have limited capacity to predict IBD-U and reclassification during follow-up. In terms of antibody profiles, IBD-U is not a distinct subtype of IBD.

Mental health of migrants with pre-migration exposure to armed conflict: a systematic review and meta-analysis.

BACKGROUND: Exposure to armed conflict has been associated with negative mental health consequences. We aimed to estimate the prevalence of generalised anxiety disorder, major depressive disorder, and post-traumatic stress disorder among migrants exposed to armed conflict. METHODS: In this systematic review and meta-analysis, we searched online databases (Cochrane Library, Embase, LILACS, PsycInfo [via Ovid], PubMed, and Web of Science Core Collection) for relevant observational studies published between Jan 1, 1994, and June 28, 2021. We included studies that used standardised psychiatric interviews to assess generalised anxiety disorder, major depressive disorder, or post-traumatic stress disorder among migrants (refugees or internally displaced persons; aged ≥18 years) with pre-migration exposure to armed conflict. We excluded studies in which exposure to armed conflict could not be ascertained, studies that included a clinical population or people with chronic diseases that can trigger the onset of mental disease, and studies published before 1994. We used a random effects model to estimate each mental health disorder's pooled prevalence and random effects meta-regression to assess sources of heterogeneity. Two independent reviewers assessed the risk of bias for each study using the Joanna Briggs Institute Checklist for Prevalence Studies. The protocol was registered with PROSPERO, CRD42020209251. FINDINGS: Of the 13 935 studies identified, 34 met our inclusion criteria; these studies accounted for 15 549 migrants. We estimated a prevalence of current post-traumatic stress disorder of 31% (95% CI 23-40); prevalence of current major depressive disorder of 25% (17-34); and prevalence of generalised anxiety disorder of 14% (5-35). Younger age was associated with a higher prevalence of current post-traumatic stress disorder (odds ratio 0·95 [95% CI 0·90-0·99]), lifetime post-traumatic stress disorder (0·88 [0·83-0·92]), and current generalised anxiety disorder (0·87 [0·78-0·97]). A longer time since displacement was associated with a lower lifetime prevalence of post-traumatic stress disorder (0·88 [0·81-0·95]) and major depressive disorder (0·81 [0·77-0·86]). Migrating to a middle-income (8·09 [3·06-21·40]) or low-income (39·29 [11·96-129·70]) country was associated with increased prevalence of generalised anxiety disorder. INTERPRETATION: Migrants who are exposed to armed conflict are at high risk of mental health disorders. The mental health-care needs of migrants should be assessed soon after resettlement, and adequate care should be provided, with particular attention paid to young adults. FUNDING: Marie Sklodowska-Curie Actions (Horizon 2020-COFUND), MinCiencias (Colombia), and Swiss National Science Foundation.

GLP-1 Receptor Agonists and Coronary Arteries: From Mechanisms to Events.

Objective: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) lower plasma glucose through effects on insulin and glucagon secretion and by decelerating gastric emptying. GLP-1 RAs have many beneficial effects beyond glycemic control, including a protective role on the cardiovascular system. However, underlying mechanisms linking GLP-1 RAs with coronary artery disease are complex and not fully elucidated. In this mini-review, we discuss these mechanisms and subsequent clinical events. Data Sources: We searched PubMed and Google Scholar for evidence on GLP-1 RAs and coronary events. We did not apply restrictions on article type. We reviewed publications for clinical relevance. Synopsis of Content: In the first part, we review the current evidence concerning the role of GLP-1 RAs on potential mechanisms underlying the development of coronary events. Specifically, we discuss the role of GLP-1 RAs on atherosclerosis and vasospasms of epicardial coronary arteries, as well as structural/functional changes of coronary microvasculature. In the second part, we summarize the clinical evidence on the impact of GLP-1 RAs in the prevention of acute and chronic coronary syndromes and coronary revascularization. We conclude by discussing existing gaps in the literature and proposing directions for future research.

The Role of SGLT2 Inhibitors in Atherosclerosis: A Narrative Mini-Review.

Objective: Sodium glucose cotransporter 2 inhibitors (SGLT2-is) are antidiabetic drugs that improve glycemic control by limiting urinary glucose reuptake in the proximal tubule. SGLT2-is might suppress atherosclerotic processes and ameliorate the prognosis of patients with diabetes mellitus diagnosed with or at high risk of atherosclerotic cardiovascular disease (ASCVD). In this mini review, we examine the role of SGLT2-is in the development and progression of atherosclerosis throughout its spectrum, from subclinical atherosclerosis to ASCVD. Data Sources-PubMed and Google Scholar were searched for publications related to SGLT2-is and atherosclerosis. All types of articles were considered, including clinical trials, animal studies, in vitro observations, and reviews and meta-analyses. Data were examined according to their impact and clinical relevance. Synopsis of Content-We first review the underlying mechanisms of SGLT2-is on the development and progression of atherosclerosis, including favorable effects on lipid metabolism, reduction of systemic inflammation, and improvement of endothelial function. We then discuss the putative impact of SGLT2-is on the formation, composition, and stability of atherosclerotic plaque. Furthermore, we evaluate the effects of SGLT2-is in subclinical atherosclerosis assessed by carotid intima media thickness and pulse wave velocity. Subsequently, we summarize the effects of SGLT2-is in ASCVD events, including ischemic stroke, angina pectoris, myocardial infarction, revascularization, and peripheral artery disease, as well as major adverse cardiovascular events, cardiovascular mortality, heart failure, and chronic kidney disease. Moreover, we examine factors that could modify the role of SGLT2-is in atherosclerosis, including sex, age, diabetes, glycemic control, ASCVD, and SGLT2-i compounds. Additionally, we propose future directions that can improve our understanding of SGLT2-is and atherosclerosis.

PD-1/PD-L1-Associated Immunoarchitectural Patterns Stratify Pancreatic Cancer Patients into Prognostic/Predictive Subgroups.

Immunotherapy, including PD-1/PD-L1 agonists, has shown limited efficacy in pancreatic ductal adenocarcinoma (PDAC). We examined the PD-1/PD-L1 expression and immunoarchitectural features by automated morphometric analysis using multiplex immunofluorescence and 118 microsatellite-stable, treatment-naïve, surgically resected PDACs (study cohort). Five microsatellite-instable cases were stained in parallel (MSI cohort). Molecular analysis was additionally performed. An independent PDAC cohort (n = 226) was immunostained for PD-L1 and used as a validation cohort. PD-L1 expression on tumor cells (TC) and/or immune cells (IC) was present in 32% and 30% of the study and validation cohorts, respectively, and assigned into one of four patterns: "adaptive-1" (TC: 0, IC > 1%), "adaptive-2" (TC > 1% to < 25%, IC > 1%), "constitutive" (TC ≥ 25%, IC: 0), and "combined" (TC ≥ 25%, IC > 1%). "Constitutive" tumors were characterized by reduced numbers of all ICs and poor outcome. In contrast, "adaptive-1" tumors exhibited abundant T cells, including high counts of cytotoxic CD3+CD8+ and PD-1+CD3+CD8+ cells, but low counts of PD-L1+CD3+CD8+ cells and associated with the best outcome. "Adaptive-2" tumors displayed higher proportions of PD-L1+CD3+CD8+ T cells and tumor-associated macrophages (CD68+ and CD68+CD206+) compared with "adaptive-1" tumors. In the "combined" pattern, extensive PD-L1 expression on TCs was accompanied by increased numbers of T cells and improved overall survival. ICs were closer to PD-L1- than to PD-L1+ PDAC cells. TP53 and PIK3CA alterations tended to be more frequent in PD-L1+ tumors. The 5 MSI cases were PD-L1- The distinct PD-1/PD-L1-associated immunoarchitectural patterns underpin the heterogeneity of the immunologic responses and might be used to inform patient outcomes and therapeutic decisions in pancreatic cancer.

Exploratory Analysis of Qualitative MR Imaging Features for the Differentiation of Glioblastoma and Brain Metastases.

OBJECTIVES: To identify qualitative VASARI (Visually AcceSIble Rembrandt Images) Magnetic Resonance (MR) Imaging features for differentiation of glioblastoma (GBM) and brain metastasis (BM) of different primary tumors. MATERIALS AND METHODS: T1-weighted pre- and post-contrast, T2-weighted, and T2-weighted, fluid attenuated inversion recovery (FLAIR) MR images of a total of 239 lesions from 109 patients with either GBM or BM (breast cancer, non-small cell (NSCLC) adenocarcinoma, NSCLC squamous cell carcinoma, small-cell lung cancer (SCLC)) were included. A set of adapted, qualitative VASARI MR features describing tumor appearance and location was scored (binary; 1 = presence of feature, 0 = absence of feature). Exploratory data analysis was performed on binary scores using a combination of descriptive statistics (proportions with 95% binomial confidence intervals), unsupervised methods and supervised methods including multivariate feature ranking using either repeated fitting or recursive feature elimination with Support Vector Machines (SVMs). RESULTS: GBMs were found to involve all lobes of the cerebrum with a fronto-occipital gradient, often affected the corpus callosum (32.4%, 95% CI 19.1-49.2), and showed a strong preference for the right hemisphere (79.4%, 95% CI 63.2-89.7). BMs occurred most frequently in the frontal lobe (35.1%, 95% CI 28.9-41.9) and cerebellum (28.3%, 95% CI 22.6-34.8). The appearance of GBMs was characterized by preference for well-defined non-enhancing tumor margin (100%, 89.8-100), ependymal extension (52.9%, 36.7-68.5) and substantially less enhancing foci than BMs (44.1%, 28.9-60.6 vs. 75.1%, 68.8-80.5). Unsupervised and supervised analyses showed that GBMs are distinctively different from BMs and that this difference is driven by definition of non-enhancing tumor margin, ependymal extension and features describing laterality. Differentiation of histological subtypes of BMs was driven by the presence of well-defined enhancing and non-enhancing tumor margins and localization in the vision center. SVM models with optimal hyperparameters led to weighted F1-score of 0.865 for differentiation of GBMs from BMs and weighted F1-score of 0.326 for differentiation of BM subtypes. CONCLUSION: VASARI MR imaging features related to definition of non-enhancing margin, ependymal extension, and tumor localization may serve as potential imaging biomarkers to differentiate GBMs from BMs.