Pemetrexed, a multitarget antifolate used to treat malignant mesothelioma and non-small cell lung cancer (NSCLC), has been shown to stimulate autophagy. In this study, we determined whether autophagy could be induced by pemetrexed and simvastatin cotreatment in malignant mesothelioma and NSCLC cells. Furthermore, we determined whether inhibition of autophagy drives apoptosis in malignant mesothelioma and NSCLC cells. Malignant mesothelioma MSTO-211H and A549 NSCLC cells were treated with pemetrexed and simvastatin alone and in combination to evaluate their effect on autophagy and apoptosis. Cotreatment with pemetrexed and simvastatin induced greater caspase-dependent apoptosis and autophagy than either drug alone in malignant mesothelioma and NSCLC cells. 3-Methyladenine (3-MA), ATG5 siRNA, bafilomycin A, and E64D/pepstatin A enhanced the apoptotic potential of pemetrexed and simvastatin, whereas rapamycin and LY294002 attenuated their induction of caspase-dependent apoptosis. Our data indicate that pemetrexed and simvastatin cotreatment augmented apoptosis and autophagy in malignant mesothelioma and NSCLC cells. Inhibition of pemetrexed and simvastatin-induced autophagy was shown to enhance apoptosis, suggesting that this could be a novel therapeutic strategy against malignant mesothelioma and NSCLC.

Background/AimsPleuropulmonary paragonimiasis produces no specific symptoms or radiologic findings, allowing for the possibility of misdiagnosis. We evaluated the specific clinical and pleural fluid features of pleuropulmonary paragonimiasis masquerading as pleural tuberculosis.MethodsWe retrospectively analyzed the clinical and radiologic characteristics of 20 patients diagnosed with pleuropulmonary paragonimiasis between 2001 and 2011.ResultsIn total, 17 patients presented with respiratory symptoms, including dyspnea (30%), hemoptysis (20%), cough (20%), and pleuritic chest pain (15%). Chest radiographs revealed intrapulmonary parenchymal lesions, including air-space consolidation (30%), nodular opacities (20%), cystic lesions (15%), ground-glass opacities (10%), and pneumothorax (5%). A pleural f luid examination revealed eosinophilia, low glucose levels, and high lactate dehydrogenase (LDH) levels in 87%, 76%, and 88% of the patients, respectively. These traits helped to distinguish pleuropulmonary paragonimiasis from other pleural diseases such as parapneumonic effusion, malignancy, and pleural tuberculosis.ConclusionsPleuropulmonary paragonimiasis is often initially misdiagnosed as other pleural diseases. Therefore, it is important to establish the correct diagnosis. In patients with unexplained pleural effusion living in paragonimiasis-endemic areas, pleural fluid obtained by thoracentesis should be examined to distinguish pleuropulmonary paragonimiasis. When marked eosinophilia, high LDH levels, and low glucose levels are identified in pleural fluid, physicians could consider a diagnosis of pleuropulmonary paragonimiasis.

Systemic immune-inflammation index (SII, platelet × neutrophil/lymphocyte ratio) has recently been identified as an inflammatory marker. We aimed to evaluate the prognostic implications of preoperative SII in patients undergoing isolated tricuspid valve (TV) surgery. In total, 213 patients who underwent isolated TV surgery between January 2000 and December 2018 were enrolled. They were divided into two groups, as follows: low SII (<455.6 × 109/L), and high SII (≥455.6 × 109/L). The correlation between SII and clinical outcomes was analyzed via the Cox regression and the Kaplan–Meier analyses. The primary outcomes considered were all-cause mortality and major postoperative complications within a 30-day period after isolated TV surgery, including major adverse cardiovascular or cerebrovascular events, pulmonary and renal complications, stroke, sepsis, multi-organ failure, wound, and gastrointestinal complications. In total, 82 (38.5%) patients experienced postoperative complications. Multivariable analyses revealed that high preoperative SII values were independently associated with the major 30-day postoperative complications (hazard ratio 3.58, 95% confidence interval 1.62–7.95, p = 0.001). Additionally, Kaplan–Meier analysis revealed that the probability of undergoing major 30-day postoperative complications was significantly elevated in patients with high versus low SII values (p < 0.001). These results indicate that SII, a readily available parameter, is significantly associated with poor outcomes in patients undergoing isolated TV surgery.

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