Cover Image,Volume 20, Issue 4

The cover image, by Inmaculada Ruz‐Maldonado et al., is based on the Original Article LH‐21 and abnormal cannabidiol improve β‐cell function in isolated human and mouse islets through GPR55‐dependent and ‐independent signalling, DOI: 10.1111/dom.13180 .

     

Variable susceptibility to dynamic coronary obstruction: An elusive link between coronary atherosclerosis and angina pectoris

Growing evidence suggests that dynamic coronary obstructions play an important but elusive role in the genesis of ischemic events. Dynamic coronary obstructions can develop during certain phases of coronary disease as a result of a variable combination of vasoconstriction, arterial wall lesions, and increased thrombotic tendency. In a certain phase of their disease some patients develop dynamic coronary obstruction, while others with a similar degree of fixed atherosclerotic obstruction do not.     

Evaluation of the effects of catheter sampling for the study of platelet behavior in the pulmonary and coronary circulation

To study the effects of sampling through cardiac catheters on indices of platelet function, we measured the levels of platelet factor 4 (PF₄), beta thromboglobulin (BTG), and platelet aggregate ratio (PAR) in 10 patients with atrioventricular accessory pathway (AVNAP), six patients with primary pulmonary hypertension (PPH), and six patients with critical narrowing of the left anterior descending artery (LAD). In AVNAP and LAD patients samples were drawn simultaneously from a peripheral vein, coronary sinus, and brachial artery; in AVNAP patients samples were also obtained from the axillary vein before the coronary sinus was entered. In PPH patients samples were drawn from pulmonary artery, aorta, and a peripheral vein; in these patients the effects of an intravenous infusion of prostacyclin (PGl₂) (2 to 8 ng/kg/min) on PF₄, BTG, and PAR were also studied at all sampling sites. In all patients arterial, coronary sinus, pulmonary arterial, and axillary venous levels of PF₄, BTG, and PAR significantly exceeded those measured in the peripheral vein. PGl₂ infusion resulted in a significant decrease of PF₄ at all sampling sites, while no consistent BTG changes were observed and PAR levels did not decrease in the peripheral vein. Although a considerable interpatient variability in PF₄ levels was observed, a significant (r = 0.91) correlation was found in patients with AVNAP between simultaneous coronary sinus and arterial PF₄ levels. The value of PF₄ coronary sinus-arterial difference in LAD patients was consistently higher than that calculated in AVNAP patients (54.5 ± 28.9 vs 4.2 ± 3.8 ng/ml). In conclusion: (1) a considerable and variable degree of platelet activation occurs with catheter sampling, preventing the measurement of absolute levels of platelet metabolites; (2) among the indices examined PF₄ appears the most sensitive for detecting changes in platelet activity; and (3) the measurement of coronary sinus-arterial PF₄ differences may provide information on directional changes in transcardiac platelet behavior.     

Gut microbiota imbalance and chaperoning system malfunction are central to ulcerative colitis pathogenesis and can be counteracted with specifically designed probiotics: a working hypothesis

In this work, we propose that for further studies of the physiopathology and treatment for inflammatory bowel diseases, an integral view of the conditions, including the triad of microbiota–heat shock proteins (HSPs)–probiotics, ought to be considered. Microbiota is the complex microbial flora that resides in the gut, affecting not only gut functions but also the health status of the whole body. Alteration in the microbiota’s composition has been implicated in a variety of pathological conditions (e.g., ulcerative colitis, UC), involving both gut and extra-intestinal tissues and organs. Some of these pathologies are also associated with an altered expression of HSPs (chaperones) and this is the reason why they may be considered chaperonopathies. Probiotics, which are live microorganisms able to restore the correct, healthy equilibrium of microbiota composition, can ameliorate symptoms in patients suffering from UC and modulate expression levels of HSPs. However, currently probiotic therapy follows ex-adiuvantibus criteria, i.e., treatments with beneficial effects but whose mechanism of action is unknown, which should be changed so the probiotics needed in each case are predetermined on the basis of the patient’s microbiota. Consequently, efforts are necessary to develop diagnostic tools for elucidating levels and distribution of HSPs and the microbiota composition (microbiota fingerprint) of each subject and, thus, guide specific probiotic therapy, tailored to meet the needs of the patient. Microbiota fingerprinting ought to include molecular biology techniques for sequencing highly conserved DNA, e.g., genes encoding 16S RNA, for species identification and, in addition, quantification of each relevant microbe.     

Leukocyte and platelet activation in patients with giant cell arteritis and polymyalgia rheumatica: A clue to thromboembolic risks?

Ischemia is a leading causes of morbidity in giant cell arteritis (GCA). We studied circulating platelets and leukocytes in patients with GCA and with polymyalgia rheumatica. Normal healthy donors (>60 a) served as controls. Patients had a significantly greater fraction of platelets expressing P-selectin, of platelet–Nph and platelet–Mo aggregates, and of Nph and Mo expressing tissue factor. These differences were correlated with the percentage of platelets expressing P-selectin and were not influenced by clinical features or by systemic inflammation. Activated circulating leukocytes and platelets could contribute to indolent vessel inflammation and possibly to thromboembolic events in patients with systemic large vessel vasculitis.     

Association of high-risk coronary atherosclerosis at CCTA with clinical and circulating biomarkers: Insight from CAPIRE study

BackgroundHigh-risk coronary atherosclerosis features evaluated coronary CT angiography (CCTA) were suggested to have a prognostic role. The present study aimed to evaluate the association of circulating biomarkers with high-risk plaque features assessed by CCTA.MethodsA consecutive cohort of subjects who underwent CCTA because of suspected CAD was screened for inclusion in the CAPIRE study. Based on risk factors (RF) burden patients were defined as having a low clinical risk (0–1 RF with the exclusion of patients with diabetes mellitus as single RF) or an high clinical risk (≥3 RFs). In all patients, measurement of inflammatory biomarkers and CCTA analysis focused on high-risk plaque features were performed. Univariate and multivariate logistic regression analysis were used to evaluate the relationship between clinical and biological variables with CCTA advanced plaque features.Results528 patients were enrolled in CAPIRE study. Older age and male sex appeared to be predictors of qualitative high-risk plaque features and associated with the presence of elevated total, non-calcified and low-attenuation plaque volume. Among circulating biomarkers only hs-CRP was found to be associated with qualitative high-risk plaque features (OR 2.02, p = 0.004 and 2.02, p = 0.012 for LAP and RI > 1.1, respectively) with borderline association with LAP-Vol (OR 1.52, p = 0.076); HbA1c and PTX-3 resulted to be significantly associated with quantitative high-risk plaque features (OR 1.71, p = 0.003 and 1.04, p = 0.002 for LAP-Vol, respectively).ConclusionsOur results support the association between inflammatory biomarkers (hs-CRP, PTX- 3), HbA1c and high-risk atherosclerotic features detected by CCTA. Male sex and older age are significant predictors of high-risk atherosclerosis.     

Assessing the practice of data quality evaluation in a national clinical data research network through a systematic scoping review in the era of real-world data

ObjectiveTo synthesize data quality (DQ) dimensions and assessment methods of real-world data, especially electronic health records, through a systematic scoping review and to assess the practice of DQ assessment in the national Patient-centered Clinical Research Network (PCORnet).Materials and MethodsWe started with 3 widely cited DQ literature—2 reviews from Chan et al (2010) and Weiskopf et al (2013a) and 1 DQ framework from Kahn et al (2016)—and expanded our review systematically to cover relevant articles published up to February 2020. We extracted DQ dimensions and assessment methods from these studies, mapped their relationships, and organized a synthesized summarization of existing DQ dimensions and assessment methods. We reviewed the data checks employed by the PCORnet and mapped them to the synthesized DQ dimensions and methods.ResultsWe analyzed a total of 3 reviews, 20 DQ frameworks, and 226 DQ studies and extracted 14 DQ dimensions and 10 assessment methods. We found that completeness, concordance, and correctness/accuracy were commonly assessed. Element presence, validity check, and conformance were commonly used DQ assessment methods and were the main focuses of the PCORnet data checks.DiscussionDefinitions of DQ dimensions and methods were not consistent in the literature, and the DQ assessment practice was not evenly distributed (eg, usability and ease-of-use were rarely discussed). Challenges in DQ assessments, given the complex and heterogeneous nature of real-world data, exist.ConclusionThe practice of DQ assessment is still limited in scope. Future work is warranted to generate understandable, executable, and reusable DQ measures.