Elevated levels of plasma lactate dehydrogenase is an unfavorable prognostic factor in patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer, receiving treatment with gefitinib or erlotinib.

Treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has been shown to prolong survival in patients with EGFR mutation-positive non-small cell lung cancer (NSCLC). The present study performed a retrospective analysis to investigate the association between the plasma lactate dehydrogenase (LDH) levels and survival in patients with EGFR mutation-positive NSCLC receiving treatment with EGFR-TKIs. The medical charts of patients with EGFR mutation-positive NSCLC who were receiving treatment with EGFR-TKIs at Toyama University Hospital between 2007 and 2014 were assessed. The data from 65 patients were included in the analysis. Patients with higher plasma LDH levels exhibited shorter progression-free survival (6.2 vs. 13.2 months; P<0.01) and overall survival (10.5 vs. 36.1 months; P<0.01) periods compared with patients with lower plasma LDH levels. A Cox proportional hazards model identified that the plasma LDH level was associated with the progression-free survival (P=0.05) and overall survival (P<0.01). An association was demonstrated between the pretreatment plasma LDH level and the survival in patients with EGFR mutation-positive NSCLC receiving treatment with EGFR-TKIs. Close observation is required in EGFR mutation-positive NSCLC patients exhibiting high plasma LDH levels following the initiation of treatment with EGFR-TKIs.出版社サイトへのリンク：https://doi.org/10.3892/mco.2016.77

Evaluation for effect of hypothermia on the disposition of 4-nitrophenol in rats by in-vitro metabolism study and rat liver perfusion system

Objectives The aim of this study was to evaluate the effect of hypothermia on the in-vivo pharmacokinetics of 4-nitrophenol (4NP) using rat liver homogenate and rat liver perfusion system. Methods Rat liver homogenate was incubated with 4NP, which is mainly metabolized by cytochrome P450 2E1, at 37, 34, 32 or 28°C. The Michaelis constant (Km) and maximum elimination velocity (Vmax) of 4NP were calculated by a Hanes-Woolf plot. The hepatic extraction ratio (Eh) of 4NP was evaluated in a rat liver perfusion study at 37, 34, 32 or 28°C. Moreover, the plasma concentration profiles of 4NP after its intravenous (i.v.) administration to rats were analysed by the moment theory and were compared with in-vitro parameters. Key findings While the Km of 4NP was not changed, the Vmax and Eh were reduced at low temperatures. The plasma concentrations of 4NP after its i.v. administration to rats were significantly increased at 28°C. Conclusion Changes in the pharmacokinetics of 4NP under hypothermic conditions were caused by alterations in Vmax and E h. We may be able to predict the disposition of a drug by in-vitro studies

Utility of Cardiac Rehabilitation for Long-Term Outcomes in Patients with Hospital-Acquired Functional Decline after Cardiac Surgery: A Retrospective Study

Hospital-acquired functional decline is an important outcome that affects the long-term prognosis of patients after cardiac surgery. Phase II cardiac rehabilitation (CR) for outpatients is expected to improve prognosis; however, this is not clear in patients with hospital-acquired functional decline after cardiac surgery. Therefore, this study evaluated whether phase II CR improved the long-term prognosis of patients with hospital-acquired functional decline after cardiac surgery. This single-center, retrospective observational study included 2371 patients who required cardiac surgery. Hospital-acquired functional decline occurred in 377 patients (15.9%) after cardiac surgery. The mean follow-up period was 1219 ± 682 days in all patients, and there were 221 (9.3%) cases with major adverse cardiovascular events (MACE) after discharge during the follow-up period. The Kaplan–Meier survival curves indicated that hospital-acquired functional decline and non-phase II CR was associated with a higher incidence of MACE than other groups (log-rank, p p = 0.047). Hospital-acquired functional decline after cardiac surgery and non-phase II CR were risk factors for MACE. The participation in phase II CR in patients with hospital-acquired functional decline after cardiac surgery could reduce the risk of MACE

Prognostic impact of a history of cancer and atrial fibrillation in antithrombotic therapy for chronic heart failure

Abstract Aims This study aimed to examine the prognostic significance of a history of cancer and atrial fibrillation (AF) in antithrombotic therapy for patients with chronic heart failure (CHF). Methods and results We enrolled consecutive 4876 CHF patients (69 ± 12 years; women, 31.9%) in our multicentre, hospital‐based cohort study, the Chronic Heart Failure Analysis and Registry in the Tohoku District‐2 (CHART‐2), with a median follow‐up of 8.7 years. Among them, 14% and 41% had a history of cancer and AF, respectively. AF patients with a history of cancer were older, more frequently men. History of cancer was not statistically associated with higher rate of composite of stroke, systemic thrombosis, and major bleeding defined by International Society on Thrombosis and Haemostasis [Fine–Gray sub‐distribution hazard ratio (sHR) accounting for the competing risk of all‐cause death, 0.91; 95% confidence interval (CI), 0.56–1.48; P = 0.715]. The patients with history of cancer and AF had a heightened risk for the composite of stroke, systemic thrombosis, and major bleeding (sHR, 1.64; 95% CI, 1.04–2.60; P = 0.033), especially in those aged >75 years (sHR, 2.14; 95% CI, 1.01–4.53; P = 0.046) and those with ischaemic heart disease (IHD; 2.48; 1.30–4.72; P = 0.006). Furthermore, 36% of AF patients with a history of cancer did not receive anticoagulant therapy. Conclusions The CHF patients with history of cancer and AF had higher risk for stroke, systemic thrombosis, and major bleeding, especially in the elderly and those with IHD, but considerable number of the patients did not receive anticoagulant therapy, indicating the need for better optimal anticoagulation strategy

Underuse of heart failure medications and poor long-term prognosis in chronic heart failure patients with polypharmacy – A report from the CHART-2 study

Background: In patients with chronic heart failure (CHF), comorbidities are often managed with multiple medications, characterized by polypharmacy, leading to increased risk of potentially inappropriate medication and adverse effects. Methods: We studied 4,876 consecutive patients with CHF (Stage C/D, age 69.0 ± 12.3 years) in the CHART-2 study to evaluate the association among polypharmacy, underuse of HF medications, and all-cause death. Polypharmacy was defined as the daily use of ≥ 8 medications for the survival classification and regression tree analysis. Results: The average number of medications was 10 in the polypharmacy group and 5 in the non-polypharmacy group, respectively. Over a median of 8.3 (4.1–11.7) years, the incidence rate of all-cause death was significantly higher in the polypharmacy group (n = 2,108) than in the non-polypharmacy group (57.3 % vs. 40.6 %; adjusted hazard ratio [aHR] 1.34 (95 %CI, 1.22–1.48), P < 0.001), even in age < 55 years (26.6 % vs. 14.3 %; adjusted hazard ratio [aHR] 1.61 (95 %CI, 1.04–2.50), P = 0.033). In patients with polypharmacy, those without renin-angiotensin system inhibitors (RAS-I) and/or beta-blockers (N = 1,023) were associated with increased incidence of all-cause death as compared with those with both medications (aHR 1.18; 95 %CI 1.04–1.35, P = 0.012). Conclusions: Polypharmacy was associated with poor long-term prognosis, even in younger patients with CHF. Among 4,876 patients with CHF, 1023 (20.9%) with polypharmacy and underuse of RAS-I and/or beta-blocker were associated with increased risk of all-cause death