Mapping the early dispersal patterns of SARS-CoV-2 omicron BA.4 and BA.5 subvariants in the absence of travel restrictions and testing at the borders in Europe

The circulation of SARS-CoV-2 omicron BA.4 and BA.5 subvariants with enhanced transmissibility and capacity for immune evasion resulted in a recent pandemic wave that began in April–May of 2022. We performed a statistical phylogeographic study that aimed to define the cross-border transmission patterns of BA.4 and BA.5 at the earliest stages of virus dispersal. Our sample included all BA.4 and BA.5 sequences that were publicly available in the GISAID database through mid-May 2022. Viral dispersal patterns were inferred using maximum likelihood phylogenetic trees with bootstrap support. We identified South Africa as the major source of both BA.4 and BA.5 that migrated to other continents. By contrast, we detected no significant export of these subvariants from Europe. Belgium was identified as a major hub for BA.4 transmission within Europe, while Portugal and Israel were identified as major sources of BA.5. Western and Northern European countries exhibited the highest rates of cross-border transmission, as did several popular tourist destinations in Southern and Central/Western Europe. Our study provides a detailed map of the early dispersal patterns of two highly transmissible SARS-CoV-2 omicron subvariants at a time when there was an overall relaxation of public health measures in Europe

Colour duplex sonography of temporal arteries before decision for biopsy: a prospective study in 55 patients with suspected giant cell arteritis

Although a temporal artery biopsy is the gold standard for the diagnosis of giant cell arteritis (GCA), there is considerable evidence that characteristic signs demonstrated by colour duplex sonography (CDS) of the temporal arteries may be of diagnostic importance. We aimed to test the hypothesis that CDS can replace biopsy in the algorithm for the approach to diagnose GCA. Bilateral CDS was performed in consecutive patients older than 50 years with clinically suspected GCA, as well as in 15 age- and gender-matched control subjects with diabetes mellitus and/or stroke and 15 healthy subjects, to assess flow parameters and the possible presence of a dark halo around the arterial lumen. Unilateral temporal artery biopsy was then performed in patients with suspected GCA, which was directed to a particular arterial segment in case a halo was detected in CDS. Final diagnoses, after completion of a 3-month follow-up in 55 patients, included GCA (n = 22), polymyalgia rheumatica (n = 12), polyarteritis nodosa, Wegener's, and Adamantiades-Behçet's diseases (n = 3), and neoplastic (n = 8) and infectious diseases (n = 10). A dark halo of variable size (0.7–2.0 mm) around the vessel lumen was evident at baseline CDS in 21 patients (in 12 and 9 uni- or bilaterally, respectively) but in none of the controls. The presence of unilateral halo alone yielded 82% sensitivity and 91% specificity for GCA, whereas the specificity reached 100% when halos were found bilaterally. Blood-flow abnormal parameters (temporal artery diameter, peak systolic blood-flow velocities, stenoses, occlusions) were common in GCA and non-GCA patients, as well as in healthy and atherosclerotic disease-control, elderly subjects. At follow-up CDS examinations performed at 2 and 4 weeks after initiation of corticosteroid treatment for GCA, halos disappeared in all 18 patients (9 and 9, respectively). We conclude that CDS, an inexpensive, non-invasive, and easy-to-perform method, allows a directional biopsy that has an increased probability to confirm the clinical diagnosis. Biopsy is not necessary in a substantial proportion of patients in whom bilateral halo signs can be found by CDS

Circulating Tissue Inhibitor of Matrix Metalloproteinase-4 (TIMP-4) in Systemic Sclerosis Patients with Elevated Pulmonary Arterial Pressure

Decreased levels of matrix metalloproteinases (MMPs) or excess levels of their tissue inhibitors (TIMPs) may contribute to dysregulation of extracellular matrix turnover in systemic sclerosis (SSc). In a cross-sectional study of 106 SSc patients, we measured serum levels of TIMP-4 which is preferentially expressed in cardiovascular structures and searched for correlations with simultaneously performed echocardiography measurements of pulmonary artery systolic pressure (PASP), myocardial performance, and pulmonary function tests. TIMP-4, but not MMP-9, levels were significantly raised in patients with SSc than controls. However, in the subgroup of patients with PASP measurements lower to 40 mmHg (n = 69), TIMP-4 levels were comparable to controls irrespective of the presence of diffuse or limited skin involvement, or lung fibrosis. Individual PASP measurements suggestive of pulmonary hypertension were associated with increased TIMP-4 serum levels (P = .03), independently of age, extent of skin sclerosis, or lung fibrosis, suggesting a cardiopulmonary vasculature-specific role of TIMP-4 activation in SSc

Interrelated modulation of endothelial function in Behcet's disease by clinical activity and corticosteroid treatment

Corticosteroids are commonly used in empirical treatment of Behçet's disease (BD), a systemic inflammatory condition associated with reversible endothelial dysfunction. In the present study we aimed to dissect the effects of clinical disease activity and chronic or short-term corticosteroid treatment on endothelial function in patients with BD. In a case-control, cross-sectional study, we assessed endothelial function by endothelium dependent flow mediated dilatation (FMD) at the brachial artery of 87 patients, who either were or were not receiving chronic corticosteroid treatment, and exhibiting variable clinical disease activity. Healthy individuals matched for age and sex served as controls. Endothelial function was also assessed in a prospective study of 11 patients before and after 7 days of treatment with prednisolone given at disease relapse (20 mg/day). In the cross-sectional component of the study, FMD was lower in patients than in control individuals (mean ± standard error: 4.1 ± 0.4% versus 5.7 ± 0.2%, P = 0.003), whereas there was a significant interaction between the effects of corticosteroids and disease activity on endothelial function (P = 0.014, two-factor analysis of variance). Among patients with inactive BD, those who were not treated with corticosteroids (n = 33) had FMD comparable to that in healthy control individuals, whereas those treated with corticosteroids (n = 15) had impaired endothelial function (P = 0.023 versus the respective control subgroup). In contrast, among patients with active BD, those who were not treated with corticosteroids (n = 20) had lower FMD than control individuals (P = 0.007), but in those who were receiving corticosteroids (n = 19) the FMD values were comparable to those in control individuals. Moreover, FMD was significantly improved after 7 days of prednisolone administration (3.7 ± 0.9% versus 7.6 ± 1.4%, P = 0.027). Taken together, these results imply that although corticosteroid treatment may impair endothelial function per se during the remission phase of the inflammatory process, it restores endothelial dysfunction during active BD by counteracting the harmful effects of relapsing inflammation

Late-onset psoriatic arthritis: are there any distinct characteristics? A retrospective cohort data analysis

As life expectancy increases, psoriatic arthritis (PsA) in older individuals becomes more prevalent. We explored whether late-onset versus earlier-onset PsA patients display different clinical features at diagnosis and/or during the disease course, as well as different treatment approaches and comorbidity profiles. We retrospectively collected data from consecutive PsA patients attending two rheumatology centers (December 2017–December 2022). Late-onset PsA patients (diagnosis-age: ≥60 years) were compared to those diagnosed before 60 years old. Univariate analyses and logistic regression were performed to examine for factors associated with late-onset PsA. For sensitivity analyses, the cohort’s mean diagnosis age was used as the cut-off value. Overall, 281 PsA patients were included (mean ± SD diagnosis-age: 46.0 ± 13.3 years). Of them, 14.2% (N = 40) had late-onset PsA. At diagnosis, after controlling for confounders, no demographic and clinical differences were identified. During the disease course, the late-onset group exhibited 65% fewer odds of manifesting enthesitis (adjusted Odds-ratio—adOR 0.35; 95% confidence interval 0.13–0.97), but higher frequency of dyslipidemia (adOR 3.01; 1.30–6.95) and of major adverse cardiovascular events (adOR 4.30; 1.42–12.98) compared to earlier-onset PsA group. No differences were found in the treatment approaches. In sensitivity analyses, PsA patients diagnosed after 46 (vs. ≤46) years old had an increased frequency of hypertension (adOR 3.18; 1.70–5.94) and dyslipidemia (adOR 2.17; 1.25–3.74). The present study underpins that late-onset PsA is not uncommon, while the age at PsA onset may affect the longitudinal clinical expression of the disease. Patients with late-onset PsA were less likely to manifest enthesitis but displayed increased cardiovascular risk

Interim 2-year analysis from SERENA: A real-world study in patients with psoriatic arthritis or ankylosing spondylitis treated with secukinumab

Introduction: Sustained improvement of high degree in clinical outcomes have been demonstrated in phase 3 trials with secukinumab in both psoriatic arthritis (PsA) and ankylosing spondylitis (AS). The objective of the SERENA study was to evaluate the effectiveness, retention rates, and safety of secukinumab in patients with PsA and AS. Methods: SERENA is an ongoing, longitudinal, real-world observational study involving patients with moderate-to-severe psoriasis, PsA, or AS. Patients had received at least 16 weeks of secukinumab treatment before recruitment to the study. Retention rate was defined as percentage of patients who continued secukinumab treatment over the course of study. Effectiveness of secukinumab in AS and PsA cohorts was assessed using descriptive statistics. Results: The current interim analysis included 1004 patients with PsA or AS. Overall secukinumab retention rates at 2 years after enrolment were 74.9 and 78.9% in patients with PsA and AS, respectively. At baseline and at 2 years, swollen joint count [3.3 (5.8) vs. 2.9 (5.8)], tender joint count [6.3 (9.4) vs. 5.6 (7.2)] in patients with PsA and BASDAI scores [3.2 (2.3) vs. 2.9 (2.3)] in patients with AS, suggest sustained effectiveness for patients remaining on secukinumab for at least 2 years after enrolment. A total of 73 patients had treatment interruption; 78% of these patients reinitiated secukinumab without a loading dose. No new or unexpected safety signals were reported. Conclusions: After more than 2 years since initiation, secukinumab demonstrated high retention rates and favorable safety profile as well as sustained effectiveness in patients who continued secukinumab treatment

A Powerful Paradigm for Cardiovascular Risk Stratification Using Multiclass, Multi-Label, and Ensemble-Based Machine Learning Paradigms: A Narrative Review

Background and Motivation: Cardiovascular disease (CVD) causes the highest mortality globally. With escalating healthcare costs, early non-invasive CVD risk assessment is vital. Conventional methods have shown poor performance compared to more recent and fast-evolving Artificial Intelligence (AI) methods. The proposed study reviews the three most recent paradigms for CVD risk assessment, namely multiclass, multi-label, and ensemble-based methods in (i) office-based and (ii) stress-test laboratories. Methods: A total of 265 CVD-based studies were selected using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) model. Due to its popularity and recent development, the study analyzed the above three paradigms using machine learning (ML) frameworks. We review comprehensively these three methods using attributes, such as architecture, applications, pro-and-cons, scientific validation, clinical evaluation, and AI risk-of-bias (RoB) in the CVD framework. These ML techniques were then extended under mobile and cloud-based infrastructure. Findings: Most popular biomarkers used were office-based, laboratory-based, image-based phenotypes, and medication usage. Surrogate carotid scanning for coronary artery risk prediction had shown promising results. Ground truth (GT) selection for AI-based training along with scientific and clinical validation is very important for CVD stratification to avoid RoB. It was observed that the most popular classification paradigm is multiclass followed by the ensemble, and multi-label. The use of deep learning techniques in CVD risk stratification is in a very early stage of development. Mobile and cloud-based AI technologies are more likely to be the future. Conclusions: AI-based methods for CVD risk assessment are most promising and successful. Choice of GT is most vital in AI-based models to prevent the RoB. The amalgamation of image-based strategies with conventional risk factors provides the highest stability when using the three CVD paradigms in non-cloud and cloud-based frameworks

A low-cost machine learning-based cardiovascular/stroke risk assessment system: integration of conventional factors with image phenotypes

Background: Most cardiovascular (CV)/stroke risk calculators using the integration of carotid ultrasound image-based phenotypes (CUSIP) with conventional risk factors (CRF) have shown improved risk stratification compared with either method. However such approaches have not yet leveraged the potential of machine learning (ML). Most intelligent ML strategies use follow-ups for the endpoints but are costly and time-intensive. We introduce an integrated ML system using stenosis as an endpoint for training and determine whether such a system can lead to superior performance compared with the conventional ML system.Methods: The ML-based algorithm consists of an offline and online system. The offline system extracts 47 features which comprised of 13 CRF and 34 CUSIP. Principal component analysis (PCA) was used to select the most significant features. These offline features were then trained using the event-equivalent gold standard (consisting of percentage stenosis) using a random forest (RF) classifier framework to generate training coefficients. The online system then transforms the PCA-based test features using offline trained coefficients to predict the risk labels on test subjects. The above ML system determines the area under the curve (AUC) using a 10-fold cross-validation paradigm. The above system so-called "AtheroRisk-Integrated" was compared against "AtheroRisk-Conventional", where only 13 CRF were considered in a feature set.Results: Left and right common carotid arteries of 202 Japanese patients (Toho University, Japan) were retrospectively examined to obtain 395 ultrasound scans. AtheroRisk-Integrated system [AUC=0.80, P<0.0001, 95% confidence interval (CI): 0.77 to 0.84] showed an improvement of similar to 18% against AtheroRisk-Conventional ML (AUC=0.68, P<0.0001, 95% CI: 0.64 to 0.72).Conclusions: ML-based integrated model with the event-equivalent gold standard as percentage stenosis is powerful and offers low cost and high performance CV/stroke risk assessment