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Jefferson Paril

and 2 more

Clifford TeBay

and 8 more

Background and Purpose: Hydroxychloroquine and chloroquine, alone or in combination with azithromycin, have been proposed as therapies for COVID-19. However, there is currently scant and inconsistent data regarding their proarrhythmic potential in these patients. Moreover, their risk profile in the setting of altered physiological states encountered in patients with COVID-19 (i.e. febrile state, electrolyte imbalances, and/or acidosis) is unknown. Experimental approach: Potency of hERG block was measured using high-throughput electrophysiology in the presence of variable environmental factors. These potencies informed simulations to predict population risk profiles. Effects on cardiac repolarisation were verified in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) from three separate individuals. Key Results: Chloroquine and hydroxychloroquine blocked hERG with IC50 of 1.47±0.07 µM and 3.78±0.17 µM respectively, indicating proarrhythmic risk at concentrations effective against SARS-CoV-2 in vitro and proposed in COVID-19 clinical trials. Hypokalaemia and hypermagnesemia increased potency of chloroquine and hydroxychloroquine, indicating increased proarrhythmic risk. Acidosis significantly reduced potency of all drugs (i.e. reduced proarrhythmic risk), whereas increased temperature decreased potency of chloroquine and hydroxychloroquine but increased potency for azithromycin. In silico simulations across genetically diverse populations predicted that 17% of individuals exhibit action potential durations >500 ms at the highest proposed therapeutic levels, equating to significant QT prolongation. Conclusion and Implications: Significant proarrhythmic risk is predicted for hydroxychloroquine and chloroquine at doses proposed to treat COVID-19. Clinicians should carefully consider the risk of such treatments, and implement long term QT interval monitoring in trials, particularly in patients with electrolyte imbalances.
Introduction:Cardiac anxiety(CA) is a common finding in patients in the pre- and postoperative period of coronary artery bypass graft(CABG) surgery. Ventilatory restriction generated by pain and reduced muscle strength is associated with increased CA level. Inspiratory muscle training(IMT) for generating increased muscle strength can cause a decrease in CA in the postoperative period. Objective:To evaluate the impact of IMT on inspiratory muscle strength and its relationship with cardiac anxiety in patients undergoing CABG. Methodology:This is a randomized controlled clinical trial. In the preoperative moment, all patients answered a cardiac anxiety questionnaire, composed of two domains: fear and vigilance and avoidance. In addition, their maximum inspiratory pressure(MIP) was assessed. After the surgical procedure, the patients were divided into a control group(CG) that received routine hospital care and a training group(TG) who underwent an IMT protocol until the moment of hospital discharge. Results:80 patients were evaluated,40 in each group. The IMT group showed a 17% decrease in MIP while the CG decreased 43%(p <0.01). The fear and vigilance domain had a decrease of -16±3 in the CG while in the TG the reduction was -8±3(p <0.01). The avoidance domain reduced -17±4 in the CG vs -10±4 in the TG(p <0.01). In addition, there was a strong correlation between the MIP of the TG with the domains of fear/vigilance(r -0.77) and avoidance(r -0.72). Conclusion:IMT is associated with a reduction in the loss of inspiratory muscle strength, resulting in a reduced level of cardiac anxiety in patients undergoing CABG.

Lei Lei

and 5 more

Abstract Background: Habitual snoring (HS), a prominent symptom of sleep-disordered breathing , is important to also consider the associated, multidimensional risk factors for HS in children. Aim: To identify risk factors for HS in children. Methods: A cross-sectional survey was performed in Chengdu. Children aged 2–14 years from four districts were randomly chosen to participate.Questionnaires were voluntarily completed by the children’s guardians. Results: The survey included 926 boys and 622 girls, who were an average of 7.11 5.25 years old. The sample included 463 habitual snorers (30.38%), 683 occasional snorers (44.82%), and 402 non-snorers (26.38%). HS was found in 51.84% of preschool children and 26.6% of school children.Among the HS group, 31.3% had a maternal education of a college degree or higher and 86.6%had an immediate family member who snores. Breastfeeding duration among the HS group was significantly less than among the occasional snoring and non-snoring groups. History of symptoms of allergic rhinitis, rhinosinusitis, tonsillitis, and pneumonia/bronchitis in the past six months were associated with HS. Likewise, maternal smoking during pregnancy, maternal exposure to secondhand smoke during pregnancy , and child exposure to secondhand smoke were also associated with HS. Conclusion: The prevalence of HS was higher in preschool children. Having a mother with more education, a family history of snoring, a shorter period of breastfeeding, upper respiratory tract inflammation, and passive smoking are important risk factors for HS.

Serkan Yarımoğlu

and 5 more

Objectives: In this study, we aimed to compare the outcomes and complication rates of percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS) in geriatric patients according to Charlson comorbidity index (CCI). Materials and Methods: Between April 2011 and January 2020, patients who underwent PCNL and RIRS for renal stone between 10 and 30 mm in geriatric patients were retrospectively evaluated. All patients’ Pre-surgery comorbidities were recorded and the CCI was calculated. The two groups’ perioperative values, stone free rates and complication rates were compared. Postoperative complications were noted according to the Clavien scoring system. Results: There were 89 and 72 patients in the PCNL and RIRS group, respectively. The median age was 67 years in both of groups (p=0.192). The stone size were 22.2 ± 3.5 and 19.9 ± 7.1 in the PCNL and RIRS group, respec¬tively ( p = 0.082). CCI scores were similar in both groups (p=0.098). Stone free and complication rates were significantly higher in PCNL group (p = 0.021, p = 0.034). Also we found that overall complication and major complication rates were statistically significant difference with especially Charlson comorbidity index score ≥2 in PCNL group (p = 0,016, p = 0,029). According to correlation analysis of intraoperative and postoperative results with Charlson comorbidity index, there was positive correlation between total complication with PCNL and RIRS group, respectively (p < 0,001, p = 0.024). In addition, there was positive correlation between lenght of hospital stay with PCNL and RIRS group, respectively (p = 0,007, p < 0,001). Also there was positive correlation between blood transfusion requirement with PCNL group (p=0,009). Conclusion: Despite there was higher stone clearence in PCNL, the complication rates were higher compared to RIRS. So RIRS might be a safe alternative treatment method to PCNL in older patients with a high CCI score.

Zhe Xu

and 5 more

Leaf rust of wheat caused by Puccinia triticina (Pt) is one of the most common and widespread fungal diseases which has a wide incidence area, especially in the southwest and northwest of China, the middle and lower reaches of the Yangtze river, and the southern part of the Huang-huai-hai river basin. To explore the relationship between the epidemic flora of leaf rust and transmission, a total of 709 isolates from Beijing, Hebei, Henan, Shandong, Shanxi, Shaanxi, Anhui, Jiangsu, Hubei, Yunnan, Sichuan, Gansu, Qinghai, Heilongjiang, Inner Mongolia 15 provinces was genotyped using 13 simple sequence repeat (SSR) markers. The Puccinia triticina populations from the 15 provinces were obviously divided into three predominant populations including the eastern Pt populations consisting of Pt samples from eight eastern provinces of Beijing, Hebei, Shandong, Anhui, Henan, Shanxi, Shaanxi and Heilongjiang; the four western Pt populations from Gansu, Sichuan, Qinghai and Inner Mongolia provinces; and the bridge Pt populations including Pt samples from Jiangsu, Hubei and Yunnan provinces which were communicated with the other two populations as a “bridge”. And the pathogen source transmission of eastern Pt populations was more frequent than western Pt populations. The linkage disequilibrium test indicated that the whole Pt population was linkage disequilibrium. Beijing, Hebei, Shaanxi, Jiangsu, Henan and Heilongjiang provinces were showed obviously linkage equilibrium phenomena while the five provinces of Qinghai, Hubei, Anhui, Shandong and Inner Mongolia were supported clonal mode of reproductions. In addition, provinces of Shanxi, Yunnan, Gansu, and Sichuan showed weak linkage disequilibrium phenomena. We systematically revealed the genotypic diversities, population differentiation and reproduction of P. triticina in 15 wheat producing areas in China.

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Gunter Sturm

and 38 more

Background: There is controversy whether taking β-blockers or ACE inhibitors (ACEI) is a risk factor for more severe systemic insect sting reactions (SSR) and whether it increases the number or severity of adverse events (AE) during venom immunotherapy (VIT). Methods: In this open, prospective, observational, multicenter trial, we recruited patients with a history of a SSR and indication for VIT. The primary objective of this study was to evaluate whether patients taking β-blockers or ACEI show more systemic AE during VIT compared to patients without such treatment. Results: In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. Of all patients included, 388 (27.2%) took antihypertensive (AHT) drugs (10.4% took β-blockers, 11.9% ACEI, 5.0% β-blockers and ACEI). Only 5.6% of patients under AHT treatment experienced systemic AE during VIT as compared with 7.4% of patients without these drugs (OR: 0.74, 95% CI: 0.43–1.22, p=0.25). The severity of the initial sting reaction was not affected by the intake of β-blockers or ACEI (OR: 1.14, 95% CI: 0.89–1.46, p=0.29). In total, 210 (17.7%) patients were re-stung during VIT and 191 (91.0%) tolerated the sting without systemic symptoms. Of the 19 patients with VIT treatment failure, 4 took β-blockers, none an ACEI. Conclusions: This trial provides robust evidence that taking β-blockers or ACEI does neither increase the frequency of systemic AE during VIT nor aggravate SSR. Moreover, results suggest that these drugs do not impair effectiveness of VIT. (Funded by Medical University of Graz, Austria; number, NCT04269629)

Nazanin Kermani

and 12 more

Background. Patients with severe asthma may have a greater risk of dying from COVID-19 disease. Angiotensin converting enzyme-2 (ACE2) and the enzyme proteases, transmembrane protease serine 2 (TMPRSS2) and FURIN, are needed for viral attachment and invasion into host cells. Methods. We examined microarray mRNA expression of ACE2, TMPRSS2 and FURIN in sputum, bronchial brushing and bronchial biopsies of the European U-BIOPRED cohort. Clinical parameters and molecular phenotypes, including asthma severity, sputum inflammatory cells, lung functions, oral corticosteroid (OCS) use, and transcriptomic-associated clusters, were examined in relation to gene expression levels. Results. ACE2 levels were significantly increased in sputum of severe asthma compared to mild-moderate asthma. In multivariate analyses, sputum ACE2 levels were positively associated with OCS use and male gender. Sputum FURIN levels were significantly related to neutrophils (%) and the presence of severe asthma. In bronchial brushing samples, TMPRSS2 levels were positively associated with male gender and body mass index, whereas FURIN levels with male gender and blood neutrophils. In bronchial biopsies, TMPRSS2 levels were positively related to blood neutrophils. The neutrophilic molecular phenotype characterised by high inflammasome activation expressed significantly higher FURIN levels in sputum than the eosinophilic Type 2-high or the pauci-granulocytic oxidative phosphorylation phenotypes. Conclusion. Levels of ACE2 and FURIN may differ by clinical or molecular phenotypes of asthma. Sputum FURIN expression levels were strongly associated with neutrophilic inflammation and with inflammasome activation. This might indicate the potential for a greater morbidity and mortality outcome from SARS-CoV-2 infection in neutrophilic severe asthma.

Xinyi Guan

and 4 more

Fabio Ramponi

and 6 more

Coronary artery and cerebrovascular disease represent a major cause of cardiovascular morbidity and mortality worldwide. Despite technological advancements in percutaneous interventions, surgical revascularization remains the preferred strategy in patients with left main or multivessel disease and in those with complex lesions with high SYNTAX score. As a result, an increasing number of older patients with diffuse atherosclerotic extracoronary disease are referred for coronary artery bypass grafting (CABG). Cerebrovascular complications after isolated coronary surgery occurs in 1-5% of patients; the magnitude of injury ranges from overt neurologic lesions with varying degree of permanent disability to “asymptomatic” cerebral events detected by dedicated neuro-imaging, nevertheless associated with significant long term cognitive and functional decline. Thromboembolic events due to manipulation of an atherosclerotic aorta are universally recognized as the leading etiology of early postoperative stroke following CABG. Coronary bypass surgery performed on an arrested heart relies on considerable aortic instrumentation associated with significant atheroembolic risk especially in older patients presenting with diffuse aortic calcifications. Surgical techniques to deal with a calcified ascending aorta during isolated coronary surgery have evolved over the last forty years. Moving away from aggressive aortic debridement or replacement, surgeons have developed strategies aimed to minimize aortic manipulation: from pump-assisted beating heart surgery with the use of composite grafts to complete avoidance of aortic manipulation with “anaortic” off-pump coronary artery bypass grafting, a safe and effective approach in significantly reducing the risk of intraoperative stroke.

Oktay Ucer

and 3 more

Nada A. Saad

and 3 more

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