Metabolic syndrome in Zambian adults with human immunodeficiency virus on antiretroviral therapy: Prevalence and associated factors

Metabolic syndrome (MetS) is a constellation of factors including hypertension, abdominal obesity, dyslipidemia, and insulin resistance that separately and together significantly increase risk for cardiovascular disease (CVD) and diabetes. In sub-Saharan Africa, with a substantial burden of human immunodeficiency virus (HIV) and increasing prevalence of CVD and diabetes, there is a paucity of epidemiological data on demographic, laboratory, and clinical characteristics associated with MetS among people with HIV (people with human [PWH]). Therefore, this study aimed to determine the burden and factors influencing MetS in antiretroviral therapy (ART)-experienced individuals in Zambia.We collected cross-sectional demographic, lifestyle, anthropometric, clinical, and laboratory data in a cohort of ART-experienced (on ART for ≥6 months) adults in 24 urban HIV treatment clinics of Zambia between August, 2016 and May, 2020. MetS was defined as having ≥3 of the following characteristics: low high density lipoprotein cholesterol (HDL-c) (<1.0 mmol/L for men, <1.3 for women), elevated waist circumference (≥94 cm for men, ≥80 cm for women), elevated triglycerides (≥1.7 mmol/L), elevated fasting blood glucose (≥5.6 mmol/L), and elevated blood pressure (BP) (systolic BP ≥130 or diastolic BP ≥85 mm Hg). Virological failure (VF) was defined as HIV viral load ≥1000 copies/mL. The following statistical methods were used: Chi-square test, Wilcoxon rank-sum test, and multivariable logistic regression.Among 1108 participants, the median age (interquartile range [IQR]) was 41 years (34, 49); 666 (60.1%) were females. The prevalence of MetS was 26.3% (95% confidence interval [CI] 23.9–29.1). Age (adjusted odds ratio [OR] 1.07; 95% CI 1.04–1.11), female sex (OR 3.02; 95% CI 1.55–5.91), VF (OR 1.98; 95% CI 1.01–3.87), dolutegravir (DTG)-based regimen (OR 2.10; 95% CI 1.05–4.20), hip-circumference (OR 1.03; 95% CI 1.01–1.05), T-lymphocyte count (OR 2.23; 95% CI 1.44–3.43), high-sensitivity C-reactive protein (hsCRP) (OR 1.14; 95% CI 1.01–1.29), and fasting insulin (OR 1.02; 95% CI 1.01–1.04) were significantly associated with MetS.Metabolic syndrome was highly prevalent among HIV+ adults receiving ART in Zambia and associated with demographic, clinical, anthropometric, and inflammatory characteristics. The association between MetS and dolutegravir requires further investigation, as does elucidation of the impact of MetS on ART outcomes in sub-Saharan African PWH.     

Cytotoxic and apoptogenic properties of Nigella sativa and thymoquinone,its constituent,in human renal cell carcinoma are comparable with cisplatin

Renal cell carcinoma (RCC) is the most common renal malignancy in adults and exhibits highly intrinsic and acquired resistance to standard therapeutic strategies. We sought to determine the anti-cancer activity of hydroalcoholic extract of Nigella sativa seeds (NSE) and thymoquinone (TQ). Human renal cell carcinoma (ACHN) and fibroblast L929 cell lines were treated with NSE and TQ, and cytotoxicity was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay. Cell death pattern was determined by annexin V and propidium iodine (PI)-staining methods. Exposure to NSE, TQ and cisplatin significantly inhibited the growth of ACHN cells and showed significant increase of early apoptotic cells. Normal cells were more resistant to NSE and TQ-induced effects. The present study demonstrates that N. sativa and TQ exert anti-proliferative and pro-apoptotic effects on ACHN cells in a concentration and time-dependent manner, which suggests their potential to be used as a new therapeutic strategy for renal cancers.     

Inhibitory effect of Crocus sativus L. ethanol extract on adjuvant-induced arthritis

Saffron is a well-known spice produced from dried stigmas of Crocus sativus L. flowers. Apart from its wide use in food preparations, it also has a broad range of medical properties. We examined the potential anti-inflammatory effects of saffron ethanolic extract (SEE) using an animal model of arthritis. Adjuvant-induced arthritis was induced in Wistar rats by injection of Complete Freund's Adjuvant. The rats were then injected intraperitoneally every other day with 25–600 mg SEE/kg or dexamethasone (DEX, 2 mg/kg). Changes in body weight, paw oedema and arthritis indices were recorded over the subsequent 12 days of treatment. Results revealed that SEE particularly at the higher concentrations significantly reduced paw and tibiotarsal joint diameters and comparing with DEX caused no significant change in body weight. These observations suggest that SEE displays a considerable anti-inflammatory potency and could potentially be used as an anti-arthritic agent in control of inflammation in rheumatoid arthritis.     

Prospective Evaluation of Transseptal TMVR for Failed Surgical Bioprostheses: MITRAL Trial Valve-in-Valve Arm 1-Year Outcomes

ObjectivesThe aim of this study was to assess 1-year clinical outcomes among high-risk patients with failed surgical mitral bioprostheses who underwent transseptal mitral valve-in-valve (MViV) with the SAPIEN 3 aortic transcatheter heart valve (THV) in the MITRAL (Mitral Implantation of Transcatheter Valves) trial.BackgroundThe MITRAL trial is the first prospective study evaluating transseptal MViV with the SAPIEN 3 aortic THV in high-risk patients with failed surgical mitral bioprostheses.MethodsHigh-risk patients with symptomatic moderate to severe or severe mitral regurgitation (MR) or severe mitral stenosis due to failed surgical mitral bioprostheses were prospectively enrolled. The primary safety endpoint was technical success. The primary THV performance endpoint was absence of MR grade ≥2+ or mean mitral valve gradient ≥10 mm Hg (30 days and 1 year). Secondary endpoints included procedural success and all-cause mortality (30 days and 1 year).ResultsThirty patients were enrolled between July 2016 and October 2017 (median age 77.5 years [interquartile range (IQR): 70.3 to 82.8 years], 63.3% women, median Society of Thoracic Surgeons score 9.4% [IQR: 5.8% to 12.0%], 80% in New York Heart Association functional class III or IV). The technical success rate was 100%. The primary performance endpoint in survivors was achieved in 96.6% (28 of 29) at 30 days and 82.8% (24 of 29) at 1 year. Thirty-day all-cause mortality was 3.3% and was unchanged at 1 year. The only death was due to airway obstruction after swallowing several pills simultaneously 29 days post-MViV. At 1-year follow-up, 89.3% of patients were in New York Heart Association functional class I or II, the median mean mitral valve gradient was 6.6 mm Hg (interquartile range: 5.5 to 8.9 mm Hg), and all patients had MR grade ≤1+.ConclusionsTransseptal MViV in high-risk patients was associated with 100% technical success, low procedural complication rates, and very low mortality at 1 year. The vast majority of patients experienced significant symptom alleviation, and THV performance remained stable at 1 year.     

Localization of villin, a cytoskeletal protein specific to microvilli, in human ileum and colon and in colonic neoplasms

Villin is a cytoskeletal protein of microvilli of epithelial cell brush borders found principally in absorptive cells of the intestine and proximal renal tubule. A marker of both enterocyte differentiation and epithelial cell polarity, it has been studied mainly in experimental animals. We raised monoclonal antibodies to villin and used them to localize it in human ileum and colon and in 22 colonic neoplasms. Villin is localized in the brush border of normal ileum and in the luminal border of normal colon and is expressed with increasing staining intensity as cells migrate from crypt to surface. It was present in the luminal border in all five adenomas and in 16 of 17 adenocarcinomas studied. In addition, villin staining was observed in the cytoplasm of 10 tumors, and in the basement membrane area surrounding tumor in 10 cases. In "transitional" mucosa adjacent to carcinomas it was confined to the luminal border. Abnormal expression of villin by a significant proportion of colonic tumors suggests that it may have a role as a marker of colorectal neoplasia.     

Postoperative Atrial Fibrillation or Flutter Following Transcatheter or Surgical Aortic Valve Replacement: PARTNER 3 Trial

ObjectivesThe aim of this study was to assess the incidence and prognostic impact of early and late postoperative atrial fibrillation or flutter (POAF) in patients with severe aortic stenosis (AS) treated with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR).BackgroundThere is an ongoing controversy regarding the incidence, recurrence rate, and prognostic impact of early (in-hospital) POAF and late (postdischarge) POAF in patients with AS undergoing TAVR or SAVR.MethodsIn the PARTNER (Placement of Aortic Transcatheter Valve) 3 trial, patients with severe AS at low surgical risk were randomized to TAVR or SAVR. Analyses were performed in the as-treated population excluding patients with preexistent atrial fibrillation or flutter.ResultsAmong 781 patients included in the analysis, early POAF occurred in 152 (19.5%) (18 of 415 [4.3%] and 134 of 366 [36.6%] following TAVR and SAVR, respectively). Following discharge, 58 new or recurrent late POAF events occurred within 1 year following the index procedure in 55 of 781 patients (7.0%). Early POAF was not an independent predictor of late POAF following discharge (odds ratio: 1.04; 95% CI: 0.52-2.08; P = 0.90). Following adjustment, early POAF was not an independent predictor of the composite outcome of death, stroke, or rehospitalization (hazard ratio: 1.10; 95% CI: 0.64-1.92; P = 0.72), whereas late POAF was associated with an increased adjusted risk for the composite outcome (hazard ratio: 8.90; 95% CI: 5.02-15.74; P < 0.0001), irrespective of treatment modality.ConclusionsIn the PARTNER 3 trial, early POAF was more frequent following SAVR compared with TAVR. Late POAF, but not early POAF, was significantly associated with worse outcomes at 2 years, irrespective of treatment modality.     

Editor's Choice: Toward high-throughput phenotyping: unbiased automated feature extraction and selection from knowledge sources

Objective Analysis of narrative (text) data from electronic health records (EHRs) can improve population-scale phenotyping for clinical and genetic research. Currently, selection of text features for phenotyping algorithms is slow and laborious, requiring extensive and iterative involvement by domain experts. This paper introduces a method to develop phenotyping algorithms in an unbiased manner by automatically extracting and selecting informative features, which can be comparable to expert-curated ones in classification accuracy.Materials and methods Comprehensive medical concepts were collected from publicly available knowledge sources in an automated, unbiased fashion. Natural language processing (NLP) revealed the occurrence patterns of these concepts in EHR narrative notes, which enabled selection of informative features for phenotype classification. When combined with additional codified features, a penalized logistic regression model was trained to classify the target phenotype.Results The authors applied our method to develop algorithms to identify patients with rheumatoid arthritis and coronary artery disease cases among those with rheumatoid arthritis from a large multi-institutional EHR. The area under the receiver operating characteristic curves (AUC) for classifying RA and CAD using models trained with automated features were 0.951 and 0.929, respectively, compared to the AUCs of 0.938 and 0.929 by models trained with expert-curated features.Discussion Models trained with NLP text features selected through an unbiased, automated procedure achieved comparable or slightly higher accuracy than those trained with expert-curated features. The majority of the selected model features were interpretable.Conclusion The proposed automated feature extraction method, generating highly accurate phenotyping algorithms with improved efficiency, is a significant step toward high-throughput phenotyping.