Objectives The aim of this study was to test the hypothesis that angiotensin (Ang)-converting enzyme-2 (ACE2) overexpression may inhibit myocardial collagen accumulation and improve left ventricular ...(LV) remodeling and function in diabetic cardiomyopathy. Background Hyperglycemia activates the renin-Ang system, which promotes the accumulation of extracellular matrix and progression of cardiac remodeling and dysfunction. Methods Ninety male Wistar rats were divided randomly into treatment (n = 80) and control (n = 10) groups. Diabetes was induced in the treatment group by a single intraperitoneal injection of streptozotocin. Twelve weeks after streptozotocin injection, rats in the treatment group were further divided into adenovirus-ACE2, adenovirus–enhanced green fluorescent protein, losartan, and mock groups (n = 20 each). LV volume; LV systolic and diastolic function; extent of myocardial fibrosis; protein expression levels of ACE2, Ang-converting enzyme, and Ang-(1-7); and matrix metalloproteinase–2 activity were evaluated. Cardiac myocyte and fibroblast culture was performed to assess Ang-II and collagen protein expression before and after ACE2 gene transfection. Results Four weeks after ACE2 gene transfer, the adenovirus-ACE2 group showed increased ACE2 expression, matrix metalloproteinase–2 activity, and LV ejection fractions and decreased LV volumes, myocardial fibrosis, and ACE, Ang-II, and collagen expression in comparison with the adenovirus–enhanced green fluorescent protein and control groups. ACE2 was superior to losartan in improving LV remodeling and function and reducing collagen expression. The putative mechanisms may involve a shift in balance toward an inhibited fibroblast-myocyte cross-talk for collagen and transforming growth factor–beta production and enhanced collagen degradation by matrix metalloproteinase–2. Conclusions ACE2 inhibits myocardial collagen accumulation and improves LV remodeling and function in a rat model of diabetic cardiomyopathy. Thus, ACE2 provides a promising approach to the treatment of patients with diabetic cardiomyopathy.
Background Treatment with statin may be beneficial for patients with chronic kidney disease (CKD). However, the debate over the clinical importance of statin in patients with predialysis advanced CKD ...remains unresolved. Objectives The objective of the article was to evaluate the effect of statin on mortality, cerebrovascular, and renal outcomes in patients with predialysis advanced CKD and dyslipidemia. Methods Data on predialysis advanced CKD patients were retrieved from the National Health Insurance Research Database based on the guidelines for prescribing regular erythropoietin-stimulating agent in CKD patients. Patients with dyslipidemia were further selected and divided into 2 groups by their statin use after the prescribed erythropoietin-stimulating agent. All-cause mortality and cerebrovascular and renal outcomes were analyzed after propensity score matching. Results There were 2016 and 14,412 patients in the statin and nonstatin groups. Their average follow-up periods were 3.7 and 3.0 years, respectively. After 1:2 propensity score matching, the annual all-cause mortality rate was higher in the nonstatin than in the statin group (143.99 vs 109.50 per 1000 person-years; P < .001; hazard ratio: 0.73; 95% confidence interval: 0.68–080). The annual risk of ischemic stroke ( P = .186) and intracranial hemorrhage ( P = .322) were not significantly different between the 2 groups. The nonstatin group had a higher risk of dialysis than the statin group (1269.45 vs 1095.00 per 1000 person-years; P = .002). Adverse events were not significant between the 2 groups. Conclusions Statins may reduce the all-cause mortality and reduced the risk of dialysis in patients with predialysis advanced CKD and dyslipidemia. However, statins have no impact on ischemic–hemorrhage stroke.
Background “Patient empowerment” is an important component of World Health Organization hand hygiene program, but little is known about the intentions and attitude of patients/families and health ...care workers (HCWs) regarding this. Methods A cross-sectional survey using questionnaires was conducted in a tertiary teaching hospital in Taiwan to assess hand hygiene knowledge and the attitudes and intentions regarding patient empowerment among patients/families and HCWs. Results Among patients/families, 95.4% (329/345) had positive attitudes regarding patient empowerment; however, only 67.2% (232/345) had the positive intention to remind HCWs about hand hygiene ( P < .001). Risk factors for negative intention were being female (odds ratio OR, 1.82; 95% confidence interval CI: 1.08-3.03), illiteracy (OR, 3.18; 95% CI: 0.86-11.7), and being patients/families in the pediatric department (OR, 1.86; 95% CI: 0.93-3.64). Among HCWs, the difference between positive attitude (81.1%; 714/880) and positive intention regarding being reminded about hand hygiene (62.8%; 553/880) was significant ( P < .001). Risk factors for negative intention were age > 25 years (OR, 3.20; 95% CI: 1.51-6.81) and a negative attitude toward patient empowerment (OR, 10.00; 95% CI: 5.88-16.67). Conclusion There were significant gaps between attitude and intention regarding patient empowerment both among patients/families and HCWs. Special strategies targeting women, the pediatric population, or illiterate people may help improve patient/family participation. Additionally, hand hygiene education should be incorporated into early-stage medical/nursing education to create a facilitating environment. Patients/families and HCWs cooperation is needed to promote the hand hygiene program further.
Summary Background Afatinib is an irreversible ErbB-family blocker with preclinical activity in non-small-cell lung cancer (NSCLC) with EGFR mutations. We aimed to assess the efficacy of afatinib in ...patients with lung adenocarcinoma and EGFR mutations. Methods In this phase 2 study, we enrolled patients from 30 centres in Taiwan and the USA with lung adenocarcinoma (stage IIIb with pleural effusion or stage IV) with EGFR mutations, who had no more than one previous chemotherapy regimen for advanced disease, an Eastern Cooperative Oncology Group performance status of 0–2, and no previous treatment with EGFR tyrosine-kinase inhibitors. We tested two afatinib starting doses: 50 mg daily and subsequently 40 mg daily, introduced to establish whether tolerability could be improved with retention of anti-tumour activity. The primary endpoint was the proportion of patients with a confirmed objective response (complete response or partial response), on the basis of Response Evaluation Criteria in Solid Tumors 1.0 (independent review). This study is registered with ClinicalTrials.gov , number NCT00525148. Findings 129 patients were treated with afatinib, 99 with a starting dose of 50 mg and 30 with a starting dose of 40 mg. 79 (61%) of 129 patients had an objective response (two complete responses, 77 partial responses). 70 (66%) of the 106 patients with the two common activating EGFR mutations (deletion 19 or L858R) had an objective response, as did nine (39%) of 23 patients with less common mutations. Similar proportions of patients had an objective response when analysed by starting dose (18 60% of 30 patients at 40 mg vs 61 62% of 99 patients at 50 mg). Of the two most common adverse events (diarrhoea and rash or acne), grade 3 events were more common in patients receiving a 50 mg starting dose (22 22% of 99 patients for diarrhoea and 28 28% of 99 patients for rash or acne) than they were in those receiving a 40 mg starting dose (two 7% of 30 patients for both diarrhoea and rash or acne); possibly treatment-related serious adverse events were also less common in patients receiving a 40 mg starting dose (two of 30 patients vs 14 of 99 patients). We recorded one possibly drug-related death (interstitial lung disease). Interpretation Afatinib shows activity in the treatment of patients with advanced lung adenocarcinoma with EGFR mutations, especially in patients with deletion 19 or L858R mutations. The efficacy of afatinib 40 mg should be compared with chemotherapy or other EGFR tyrosine-kinase inhibitors in EGFR-mutation-positive NSCLC. Funding Boehringer Ingelheim Inc.
Background
The accuracy of current prediction tools for venous thromboembolism (VTE) events following hernia surgery remains insufficient for individualized patient management strategies. To address ...this issue, we have developed a machine learning (ML)-based model to dynamically predict in-hospital VTE in Chinese patients after hernia surgery.
Methods
ML models for the prediction of postoperative VTE were trained on a cohort of 11 305 adult patients with hernia from the CHAT-1 trial, which included patients across 58 institutions in China. In data processing, data imputation was conducted using random forest (RF) algorithm, and balanced sampling was done by adaptive synthetic sampling algorithm. Data were split into a training cohort (80%) and internal validation cohort (20%) prior to oversampling. Clinical features available pre-operatively and postoperatively were separately selected using the Sequence Forward Selection algorithm. Nine-candidate ML models were applied to the pre-operative and combined datasets, and their performance was evaluated using various metrics, including area under the receiver operating characteristic curve (AUROC). Model interpretations were generated using importance scores, which were calculated by transforming model features into scaled variables and representing them in radar plots.
Results
The modeling cohort included 2856 patients, divided into 2536 cases for derivation and 320 cases for validation. Eleven pre-operative variables and 15 combined variables were explored as predictors related to in-hospital VTE. Acceptable-performing models for pre-operative data had an AUROC ≥ 0.60, including logistic regression, support vector machine with linear kernel (SVM_Linear), attentive interpretable Tabular learning (TabNet), and RF. For combined data, logistic regression, SVM_Linear, and TabNet had better performance, with an AUROC ≥ 0.65 for each model. Based on these models, 7 pre-operative predictors and 10 combined predictors were depicted in radar plots.
Conclusions
A ML-based approach for the identification of in-hospital VTE events after hernia surgery is feasible. TabNet showed acceptable performance, and might be useful to guide clinical decision making and VTE prevention. Further validated study will strengthen this finding.
Background Primary aldosteronism is the most common cause of secondary hypertension and is associated with left ventricular hypertrophy. However, whether aldosterone excess is responsible for left ...ventricular (LV) diastolic dysfunction is unknown. Methods and Results We prospectively enrolled 129 patients with aldosterone-producing adenoma and 120 patients with essential hypertension, and analyzed their clinical, biochemical, and echocardiographic data, including tissue Doppler images. The patients with aldosterone-producing adenoma were reevaluated 1 year after adrenalectomy. After propensity score matching, there were 105 patients in each group. The patients with aldosterone-producing adenoma had worse diastolic function than the patients with essential hypertension, as reflected by lower e' (
<0.001) and higher E/e' (
=0.003). Multivariate analysis showed that LV diastolic function was significantly correlated with age (
<0.001), sex (
<0.001), body mass index (
=0.002), systolic blood pressure (
=0.004), creatinine (
=0.008), and log-transformed aldosterone-renin ratio (
=0.003). After adrenalectomy, the patients with aldosterone-producing adenoma had significant improvements in LV diastolic function as reflected by an increase in e' (
=0.003) and decrease in E/e' (
=0.002). The change in E/e' was independently correlated with baseline E/e' (
<0.001) and change in LV mass index (
=0.006). Conclusions The patients with primary aldosteronism had worse LV diastolic function than the patients with essential hypertension after propensity score matching, and this could be reversed after adrenalectomy, suggesting that aldosterone excess may induce LV diastolic dysfunction.
Background We investigated the impact of serum cholesterol levels on 30-day mortality after ischemic stroke in dialysis patients. Methods From the Taiwan Stroke Registry data, we identified 46,770 ...ischemic stroke cases, including 1101 dialysis patients and 45,669 nondialysis patients from 2006 to 2013. Results Overall, the 30-day mortality was 1.46-fold greater in the dialysis group than in the nondialysis group (1.75 versus 1.20 per 1000 person-days). The mortality rates were 1.64, .62, 2.82, and 2.23 per 1000 person-days in dialysis patients with serum total cholesterol levels of <120 mg/dL, 120-159 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Compared to dialysis patients with serum total cholesterol levels of 120-159 mg/dL, the corresponding adjusted hazard ratios of mortality were 4.20 (95% confidence interval CI = 1.01-17.4), 8.06 (95% CI = 2.02-32.2), and 6.89 (95% CI = 1.59-29.8) for those with cholesterol levels of <120 mg/dL, 160-199 mg/dL, and ≥200 mg/dL, respectively. Conclusions Dialysis patients with serum total cholesterol levels of ≥160 mg/dL or <120 mg/dL on admission are at an elevated hazard of 30-day mortality after ischemic stroke.
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