Hyperlactatemia is associated with increased risks of long-term mortality and major adverse cardiovascular events in sepsis survivors.

INTRODUCTION: Serum lactate is a potentially valuable biomarker for risk assessment for patients with sepsis, as hyperlactatemia is associated with elevated short-term mortality risks. However, the associations between hyperlactatemia and long-term clinical outcomes in sepsis survivors remain unknown. The objective of this study was to investigate whether hyperlactatemia at the time of hospitalisation for sepsis was associated with worse long-term clinical outcomes in sepsis survivors. METHODS: In total, of 4983 sepsis survivors aged ≥ 20 years were enrolled in this study between January 1, 2012, and December 31, 2018. They were divided into low (≤18 mg/dL; n = 2698) and high (>18 mg/dL; n = 2285) lactate groups. The high lactate group was then matched 1:1 by propensity-score method to the low lactate group. The outcomes of interest were all-cause mortality, major adverse cardiac events (MACEs), ischaemic stroke, myocardial infarction, hospitalisation for heart failure, and end-stage renal disease. RESULTS: After propensity score matching, the high lactate group had greater risks of all-cause mortality (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.41-1.67), MACEs (HR 1.53, 95% CI 1.29-1.81), ischaemic stroke (HR 1.47, 95% CI 1.19-1.81), myocardial infarction (HR 1.52, 95% CI 1.17-1.99), and end-stage renal disease (HR 1.42, 95% CI 1.16-1.72). Subgroup analyses stratified by baseline renal function revealed almost similarity across groups. CONCLUSION: We found that hyperlactatemia is associated with long-term risks of mortality and MACEs in sepsis survivors. Physicians may consider more aggressive and prompter management of sepsis in patients who present with hyperlactatemia to improve long-term prognoses.

Itraconazole improves survival outcomes in patients with colon cancer by inducing autophagic cell death and inhibiting transketolase expression.

The incidence of colon cancer continues to increase annually, and it is the leading cause of cancer-associated mortality worldwide. Altering cell metabolism and inducing autophagic cell death have recently emerged as novel strategies in preventing tumor growth. Autophagy plays an essential role in energy production by degrading damaged cellular components and is also associated with tumor proliferation suppression. Itraconazole is an FDA-approved drug used as an antifungal medication and has been reported to induce autophagic cell death in breast cancer. However, the effects of itraconazole on cell metabolism and induction of apoptosis in colon cancer remain unclear. The present study analyzed extensive data from patients diagnosed with colon cancer using itraconazole between January 2011 and December 2015, from the Taiwanese National Health Insurance Research Database. The underlying molecular mechanisms of itraconazole in autophagy-induced cell death were also investigated. The results demonstrated that the 5-year survival rate was significantly higher in patients with colon cancer who received itraconazole treatment. In addition, itraconazole decreased the viability and cell colony formation, and induced cleaved caspase-3 expression and G1 cell cycle arrest of COLO 205 and HCT 116 cells. Notably, itraconazole induced autophagy by enhancing LC3B and p62 expression. Following LC3 knockdown, the viability of itraconazole-treated COLO 205 and HCT 116 cells notably improved. Taken together, the results of the present study suggest that itraconazole may have a beneficial effect on patients with colon cancer, and its underlying molecular mechanisms may be associated with the induction of autophagic cell death.

Comparison of Elixhauser and Charlson Methods for Discriminative Performance in Mortality Risk in Patients with Schizophrenic Disorders.

Although Charlson Comorbidity Index scores (CCIS) and Elixhauser comorbidity index scores (ECIS) have been used to assess comorbidity in patients with schizophrenia, only CCIS, not ECIS, have been used to predict mortality in this population. This nationwide retrospective study investigated discriminative performance of mortality of these two scales in patients with schizophrenia. Exploiting Taiwan's National Health Insurance Research Database (NHRID), we identified patients diagnosed with schizophrenia discharged from hospitals between Jan 1, 1996 and Dec 31, 2007. They were followed up for subsequent death. Comorbidities presented one year prior to hospital admissions were identified and adapted to the CCIS and ECIS. Discriminatory ability was evaluated using the adjusted hazard ratio and Akaike information criterion (AIC) and Harrell's C-statistic. We identified 58,771 discharged patients with schizophrenic disorders and followed them for a mean of 10.4 years, 16.6% of whom had died. Both ECIS and CCIS were significantly associated with mortality, but ECIS had superior discriminatory ability by a lower AIC and higher Harrell's C-statistic (201231 vs. 201400; 0.856 vs. 0.854, respectively). ECIS had better discriminative performance in mortality risk than CCIS in patients with schizophrenic disorders. Its use may be encouraged for risk adjustment in this population.

Reduced risk of stroke among psychiatric patients receiving ECT: A population-based cohort study in Taiwan.

Electroconvulsive therapy (ECT) as well as the diseases it treats have been associated with stroke and cognitive impairment. We investigate the relationship between ECT and the subsequent development of stroke in patients with different severe mental illnesses. Tapping Taiwan's National Health Insurance Research Database, we identified patients diagnosed with severe mental illnesses who had received ECT between Jan 1, 2002 and Dec 31, 2007. A comparison cohort was constructed of patients who were matched by age, gender, and diagnosis but did not receive ECT. The patients were then followed up for occurrence of subsequent new-onset stroke. We identified 6264 patients had been diagnosed with mental illness and had received ECT. They were matched with 18,664 mentally ill patients who had not. The study cohort had a lower incidence of subsequent stroke than the matched controls, after controlling for age, diabetes, hypertension, coronary heart disease and enrollee sociodemographic category, risk factors for stroke in both study and control cohorts. ECT is associated with reduced risk of subsequent stroke in patients with severe mental illnesses in Taiwan. Therefore, clinicians should not let risk of stroke stop them from suggesting ECT to physically healthy patients who might benefit from this therapy.

The risks of major osteoporotic fractures in patients with schizophrenia: a population-based 10-year follow-up study.

OBJECTIVE: The aim of the study is to explore the incidence and the risks associated with major osteoporotic fractures, all-cause mortality with osteoporotic fractures and the effect of the psychiatric drug exposure in patients with schizophrenia during a 10-year follow-up period. METHODS: Two nationwide cohorts were selected from the Taiwan National Health Insurance Research Database (NHIRD) consisting of 30,335 patients with schizophrenia (age ≥ 40 years) and 121,340 age- and sex-matched control participants without schizophrenia. The psychiatric proportion of days covered (PDC) is an indicator of the intensity of drug exposure in patients with schizophrenia. The incidence and risk factors of major osteoporotic fractures were calculated for both cohorts. Additionally, the patient survival rate after major osteoporotic fractures was also calculated. RESULTS: During a 10-year follow-up period, 1677 (5.53%) schizophrenia and 4257 (3.51%) control subjects had major osteoporotic fractures (P < 0.001). The schizophrenia patients with a PDC > 0.1 showed a significantly higher incidence of major osteoporotic fractures than did the non-schizophrenia controls; however, those with a psychiatric PDC ≤ 0.1 did not. After adjustment, the psychiatric PDC was significantly and independently associated with the risk of major osteoporotic fractures except some medical morbidities but the schizophrenia diagnosis was not. In addition, among all 5934 patients with major osteoporotic fracture, the adjusted mortality hazard ratio for psychiatric PDC was 1.92 (95% CI = 1.63-2.26). CONCLUSIONS: Patients with schizophrenia are at a higher risk for major osteoporotic fractures than the general population and also have a higher mortality rate due to major osteoporotic fractures. These findings may be caused by psychiatric drug use rather than schizophrenia, which suggests that directions can be taken in future studies.

Is low individual socioeconomic status (SES) in high-SES areas the same as low individual SES in low-SES areas: a 10-year follow-up schizophrenia study.

OBJECTIVE: This study investigates the relationship between individual and neighborhood socioeconomic status (SES) and mortality among patients with schizophrenia. METHODS: A study population was identified from the National Health Insurance Research Database (NHIRD) prior to the end of 1999 that included 60,402 patients with schizophrenia. Each patient was tracked until death or to the end of 2009. Individual SESs were defined by enrollee category. Neighborhood SES was defined by enrollee category (as a proxy for occupation) and education, which were classified according to the conventions of Hollingshead. Neighborhoods were also grouped into advantaged and disadvantaged areas. The Cox proportional hazards model was used to compare the death-free survival rate between the different SES groups after adjusting for possible confounding factors and risk factors. RESULTS: During the 10-year follow-up period, the mortality rates among high, moderate, and low individual SES groups were 12.22, 14.75, and 18.48%, respectively (P < 0.001). Schizophrenia patients with low individual SESs in disadvantaged neighborhoods had a risk of death that was 18-22% higher than that of those with high individual SES in advantaged neighborhoods. The analysis of the combined effect of individual SES and neighborhood SES revealed that the death rates were highest among those with low individual SES and low neighborhood SES (P < 0.001). CONCLUSIONS: Schizophrenia patients with low individual SES in disadvantaged neighborhoods have the highest risk of mortality despite a universal health-care system. Public health strategies and welfare policies must continue to focus on this vulnerable group.

The incidence and all-cause mortality of pneumonia in patients with schizophrenia: a nine-year follow-up study.

OBJECTIVE: This study sought to estimate the incidence, all-cause mortality and relative risks for patients with schizophrenia after a pneumonia diagnosis. METHODS: The population was identified from the Taiwanese National Health Insurance Research Database (NHIRD) in 1999 and included 59,021 patients with schizophrenia and 236,084 age- and sex-matched control participants without schizophrenia. These participants were randomly selected from the 23,981,020-participant NHIRD, which contain 96% of the entire population. Using the 2000-2008 NIHRD, the incidence and nine-year pneumonia-free survival rate of pneumonia (ICD-9-CM codes 486 and 507.0-507.8) were calculated. RESULTS: Over nine years, 6055 (10.26%) patients with schizophrenia and 7844 (3.32%) controls had pneumonia. The pneumonia incidence density was 11.4/1000 person-years among the patients with schizophrenia, who experienced a 3.09-fold increased risk of developing pneumonia. After adjusting for other covariates, the patients with schizophrenia still experienced a 1.77-fold increased risk of developing pneumonia. Although, without adjustment, fewer schizophrenia patients than controls died after having pneumonia (2121 [35.12%] vs. 3497 [44.62%]), after adjusting for other variables, the mortality hazard ratio for patients with schizophrenia was 1.39. CONCLUSIONS: During a nine-year follow-up, the likelihood of developing pneumonia and all-cause mortality among patients with schizophrenia was higher than that of the non-schizophrenia group as was the mortality rate. Interestingly, the psychiatric proportion of days covered (PDC) was positively associated with pneumonia (OR: 2.51) but negatively associated with death (HR: 0.72). These findings imply the importance of iatrogenic factors and psychotropic drugs (including their benefits and side effects) and highlight the directions for future studies.

The incidence and relative risk of stroke in patients with schizophrenia: a five-year follow-up study.

OBJECTIVE: This study aimed to estimate the incidence and relative risk of stroke and post-stroke all-cause mortality in patients with schizophrenia. METHODS: This study identified a study population from the National Health Insurance Research Database (NHIRD) between 1999 and 2003 that included 80,569 patients with schizophrenia and 241,707 age- and sex-matched control participants without schizophrenia. The participants were randomly selected from the 23,981,020-participant NHIRD, which consists of 96% Taiwanese participants. Participants who had experienced a stroke between 1999 and 2003 were excluded. Using data from the NHIRD between 2004 and 2008, the incidence of stroke (ICD-9-CM code 430-438) and patient survival after stroke were calculated for both groups. After adjusting for confounding risk factors, a Cox proportional-hazards model was used to compare the five-year stroke-free survival rate to the all-cause mortality rate across the two cohorts. RESULTS: Over five years, 1380 (1.71%) patients with schizophrenia and 2954 (1.22%) controls suffered from strokes. After adjusting for demographic characteristics and comorbid medical conditions, patients with schizophrenia were 1.13 times more likely to have a stroke (95% CI=1.05-1.22; P=0.0006). In addition, 1039 (24%) patients who had a stroke died during the follow-up period. After adjusting for patient, physician and hospital variables, the all-cause mortality hazard ratio for patients with schizophrenia was 1.23 (95% CI=1.06-1.41; P=0.0052). CONCLUSIONS: During a five-year follow-up, the likelihood of developing a stroke and the all-cause mortality rate were greater among patients with schizophrenia as compared with the control group.

Factors related to incomplete flexible sigmoidoscopy among adult Chinese in Taiwan.

BACKGROUND: Sigmoidoscopy is effective in colorectal cancer screening, but incomplete examinations may overlook colonic pathologies and delay diagnosis. This study aimed to explore risk factors for incomplete insertions of flexible sigmoidoscopy among Taiwanese. METHODS: Healthy adults participating in health check-up in a tertiary medical center were invited for study. Subjects were recruited when they had fully consented and agreed to participate. Factors related to incomplete insertions of flexible sigmoidoscopy were evaluated and multivariate logistic regression was used to determine independent risk factors. A predictive model was generated by the risk factors identified. RESULTS: In total, 1,252 subjects (mean age, 53.9 13.1 years; age range, 2187 years; male/female,780/472) were enrolled, and 278 (22.2%) incomplete insertions were recorded. Multivariate analysis showed that female gender (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.562.73; p < 0.001), age >or= 60 years (OR, 1.68; 95% CI, 1.262.23; p < 0.001), inadequate bowel preparation (OR, 1.66; 95% CI, 1.212.16; p = 0.001), history of constipation (OR, 2.43; 95% CI, 1.045.69; p = 0.042), and body mass index (BMI) < 25 kg/m2 (OR, 1.41; 95% CI, 1.051.89; p = 0.024) were all independent risk factors. The probability of incomplete insertion was significantly associated with the sum of the aforementioned risk factors (p < 0.001). Compared with subjects with no risk factors, the risks of incomplete insertions increased significantly among subjects bearing 1 risk factor (OR, 2.57; 95% CI, 1.474.49; p = 0.001), 2 risk factors (OR, 4.41; 95% CI, 2.527.39; p < 0.001), 3 risk factors (OR, 6.40; 95% CI, 3.5611.52; p < 0.001) and >or= 4 risk factors (OR, 10.00; 95% CI, 3.8925.70; p < 0.001). CONCLUSION: Female sex, age >or= 60 years, BMI < 25 kg/m2, history of constipation, and inadequate bowel preparation were independent risk factors for incomplete insertion of flexible sigmoidoscopy. Subjects with multiple risk factors may consider alternative modalities for colonic examination.

Chicken heat shock protein 90 is a component of the putative cellular receptor complex of infectious bursal disease virus.

Infectious bursal disease virus (IBDV) causes a highly contagious disease in young chicks and leads to significant economic losses in the poultry industry. The capsid protein VP2 of IBDV plays an important role in virus binding and cell recognition. VP2 forms a subviral particle (SVP) with immunogenicity similar to that of the IBDV capsid. In the present study, we first showed that SVP could inhibit IBDV infection to an IBDV-susceptible cell line, DF-1 cells, in a dose-dependent manner. Second, the localizations of the SVP on the surface of DF-1 cells were confirmed by fluorescence microscopy, and the specific binding of the SVP to DF-1 cells occurred in a dose-dependent manner. Furthermore, the attachment of SVP to DF-1 cells was inhibited by an SVP-induced neutralizing monoclonal antibody against IBDV but not by denatured-VP2-induced polyclonal antibodies. Third, the cellular factors in DF-1 cells involved in the attachment of SVP were purified by affinity chromatography using SVP bound on the immobilized Ni(2+) ions. A dominant factor was identified as being chicken heat shock protein 90 (Hsp90) (cHsp90) by mass spectrometry. Results of biotinylation experiments and indirect fluorescence assays indicated that cHsp90 is located on the surface of DF-1 cells. Virus overlay protein binding assays and far-Western assays also concluded that cHsp90 interacts with IBDV and SVP, respectively. Finally, both Hsp90 and anti-Hsp90 can inhibit the infection of DF-1 cells by IBDV. Taken together, for the first time, our results suggest that cHsp90 is part of the putative cellular receptor complex essential for IBDV entry into DF-1 cells.

Intramyometrial injection of vasopressin causes bradycardia and cardiac arrest--report of two cases.

Vasopressin has been documented to effectively reduce blood loss in gynecologic practice. However, local infiltration of vasopressin may cause lethal cardiopulmonary complications in spite of rarity of reported cases. Severe bradycardia and cardiac arrest were encountered after intramyometrial injection of vasopressin in our two healthy patients undergoing open uterine myomectomy. We herewith discuss the associated complications and the anesthetic considerations.