Heart Dysfunction in Essential Hypertension Depends on Systemic Proinflammatory Influences: A Retrospective Clinical Pathophysiological Study

Low-intensity systemic inflammation is an important element of heart failure pathogenesis. The aim of this study is to assess proinflammatory status serum indicators (C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6)) in middle-aged males (M) and females (F) with essential hypertension (HTN) depending on left ventricular (LV) diastolic dysfunction (LVDD). The main group comprised 55 M and 49 F with the first- to second-severity grade HTN with mild heart failure and a preserved LV ejection fraction ≥50%. Patients had sinus rhythm, first or second-severity degree LVDD, LV hypertrophy, left atrium dilatation, and NT-proBNP > 125 pg/mL. Comparison group: 30 hypertensives without cardiac dysfunction; control group: 31 normotensives. Quantitative features were compared using the Mann–Whitney test, median χ², ANOVA module. Spearman’s rank correlation coefficients were determined to identify the relationship between the proinflammatory pattern and exercise tolerance. Hypertensive M had markedly higher CRP, TNF-α, and IL-6 levels compared to F. All mean values corresponded to reference range. In patients with second-degree LVDD, CRP, TNF-α, and IL-6 levels were significantly greater than in subjects with first-degree LVDD (both within M and within F samples). Significant negative associations between CRP, IL-6, and TNF-α levels and the 6 min walk test existed in hypertensive M and F. The study demonstrated a close relationship between the proinflammatory pattern and LVDD and exercise tolerance indicators, regardless of the hypertensive patient’s sex.     

Machine learning-based scoring system to predict in-hospital outcomes in patients hospitalized with COVID-19

BackgroundThe evolution of patients hospitalized with coronavirus disease 2019 (COVID-19) is still hard to predict, even after several months of dealing with the pandemic.AimsTo develop and validate a score to predict outcomes in patients hospitalized with COVID-19.MethodsAll consecutive adults hospitalized for COVID-19 from February to April 2020 were included in a nationwide observational study. Primary composite outcome was transfer to an intensive care unit from an emergency department or conventional ward, or in-hospital death. A score that estimates the risk of experiencing the primary outcome was constructed from a derivation cohort using stacked LASSO (Least Absolute Shrinkage and Selection Operator), and was tested in a validation cohort.ResultsAmong 2873 patients analysed (57.9% men; 66.6 ± 17.0 years), the primary outcome occurred in 838 (29.2%) patients: 551 (19.2%) were transferred to an intensive care unit; and 287 (10.0%) died in-hospital without transfer to an intensive care unit. Using stacked LASSO, we identified 11 variables independently associated with the primary outcome in multivariable analysis in the derivation cohort (n = 2313), including demographics (sex), triage vitals (body temperature, dyspnoea, respiratory rate, fraction of inspired oxygen, blood oxygen saturation) and biological variables (pH, platelets, C-reactive protein, aspartate aminotransferase, estimated glomerular filtration rate). The Critical COVID-19 France (CCF) risk score was then developed, and displayed accurate calibration and discrimination in the derivation cohort, with C-statistics of 0.78 (95% confidence interval 0.75–0.80). The CCF risk score performed significantly better (i.e. higher C-statistics) than the usual critical care risk scores.ConclusionsThe CCF risk score was built using data collected routinely at hospital admission to predict outcomes in patients with COVID-19. This score holds promise to improve early triage of patients and allocation of healthcare resources.     

Impaired exercise capacity after lung transplantation is related to delayed recovery of muscle strength

Lung transplant recipients report reduced exercise capacity despite satisfactory graft function. We analysed changes in lung function, six‐min walk distance (6MWD), and quadriceps strength in the first 26‐wk post‐transplant and examined what factors predict 6MWD recovery. All lung transplant recipients at a single institution between June 2007 and January 2011 were considered for inclusion. Lung function, 6MWD, and quadriceps strength corrected for body weight (QS%) were recorded pre‐ and two‐, six‐, 13‐, and 26‐wk post‐transplant. Fifty recipients, of mean (±SD) age 42 (±13) yr, were studied. Mean FEV₁% and 6MWD improved from 26.4% to 88.9% and from 397 to 549 m at 26 wk, respectively (both p < 0.001). QS% declined in the first two wk but had improved to above pre‐transplant levels by 26 wk (p = 0.027). On multivariate analysis (n = 35), lower pre‐transplant exercise capacity and greater recovery in muscle strength explained most of the improvement in exercise capacity. Delayed recovery of exercise capacity after lung transplantation is unrelated to delay in improvement in graft function, but occurs secondary to the slow recovery of muscle strength. Our findings show that additional controlled trials are needed to better understand the influence of exercise rehabilitation on improvement in exercise capacity post‐transplantation.     

Suitability of the AUC Ratio as an Indicator of the Pharmacokinetic Advantage in HIPEC

The purpose of this study was to evaluate the area under the concentration-time curve (AUC) ratio as an optimal indicator of the pharmacokinetic advantage during hyperthermic intraperitoneal perioperative chemotherapy. The impact on the AUC ratio on the variables related to the calculation of systemic drug exposure, instillation time, and peripheral drug distribution was evaluated through simulations as well as through a retrospective analysis of studies published in the literature. Both model simulations and the retrospective analysis showed that the 3 variables evaluated had an impact on the AUC ratio value if the complete systemic exposure was not fully considered. However, when that complete systemic exposure was considered, none of these variables affected the AUC ratio value. AUC ratio is not a characteristic parameter of a drug if the calculated systemic drug exposure is not complete. Thus, AUC ratio is not valid for comparing the pharmacokinetic advantage of 2 drugs, and it should not be employed to prove whether a drug can be used in hyperthermic intraperitoneal perioperative chemotherapy safely with regard to toxicity. As an alternative, the study of the absorption rate constant and the bioavailability are proposed as the true and independent parameters that reflect the amount of drug absorbed.     

稳心颗粒联合尼可地尔治疗缺血性心肌病合并房性心律失常患者的效果

目的:观察稳心颗粒联合尼可地尔治疗缺血性心肌病合并房性心律失常患者的效果。方法:选取103例缺血性心肌病合并房性心律失常患者作为研究对象,以电脑随机数字表法将其分为研究组51例和对照组52例。两组均开展常规基础治疗,在此基础上,对照组采用尼可地尔治疗,研究组在对照组基础上联合稳心颗粒治疗,比较两组治疗前后心功能指标[左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)、左室射血分数(LVEF)]水平、P波最大时限、P波离散度、6 min步行试验(6MWT)距离和不良反应发生率。结果:治疗后,研究组LVEDD和LVESD水平均低于对照组,LVEF水平高于对照组,6MWT距离长于对照组,差异有统计学意义(P<0.05);治疗后,研究组P波最大时限和P波离散度均小于对照组,差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论:稳心颗粒联合尼可地尔治疗缺血性心肌病合并房性心律失常患者可改善心功能指标水平,延长6MWT距离,减小P波最大时限和P波离散度,效果优于单纯尼可地尔治疗。     

Effects of combined aerobic and resistance training in patients with heart failure: A meta‐analysis of randomized,controlled trials

Cardiac rehabilitation programs consisting of core features of exercise training for patients with heart failure have demonstrated a wide range of physical and psychological benefits. In study, a meta‐analysis of combined aerobic and resistance training was conducted on various outcomes in patients with heart failure. Database searches included EMBASE, PubMed, Medline, Cochrane Library, Web of Science, OVID, and CINAHL. Only randomized, controlled trials were included. Review Manager 5.3 software was used to perform the meta‐analysis. In total, 12 studies and 516 patients were included. The results demonstrated that combined aerobic and resistance training is effective in promoting exercise capacity, muscle strength, and 6 min walk distance. Furthermore, combined training significantly improves the quality of life of patients with heart failure. However, there was no significant difference found for outcomes of depression and sleep. Future studies with rigorous methodological designs and long‐term follow ups are recommended to evaluate the sustainable benefits of combined aerobic and resistance intervention programs.