Effect of malignant-associated pleural effusion on endothelial viability, motility and angiogenesis in lung cancer.

Malignant pleural effusion (MPE) and paramalignant pleural effusion (PPE) remain debilitating complications in lung cancer patients with poor prognosis and limited treatment options. The role of vascular endothelial cells has not been explored in the pleural environment of lung cancer. By integrating MPE and PPE as malignant-associated pleural fluid (MAPF), the current study aimed to evaluate the effect of MAPF on cell proliferation, migration and angiogenesis of HUVEC. First, increased capillaries were identified in the subpleural layer of lung adenocarcinoma. Compatible with pathological observations, the ubiquitous elevation of HUVEC survival was identified in MAPF culture regardless of the underlying cancer type, the driver gene mutation, prior treatments and evidence of malignant cells in pleural fluid. Moreover, MAPF enhanced HUVEC motility with the formation of lamellipodia and filopodia and focal adhesion complex. Tube formation assay revealed angiogenic behavior with the observation of sheet-like structures. HUVEC cultured with MAPF resulted in a significant increase in MAPK phosphorylation. Accompanied with VEGFR2 upregulation in MAPF culture, there was increased expressions of p-STAT3, HIF-1α and Nf-kB. VEGF/VEGFR2 blockade regressed endothelial migration and angiogenesis but not cell proliferation. Our data indicate the angiogenic activities of MAPF on vascular endothelial cells that revealed increased pleural capillaries in lung cancer. Targeting the VEGF/VEGFR2 pathway might modulate the angiogenic propensity of MAPF in future clinical investigations.

Epigenetic Silencing of LMX1A Contributes to Cancer Progression in Lung Cancer Cells.

Epigenetic modification is considered a major mechanism of the inactivation of tumor suppressor genes that finally contributes to carcinogenesis. LIM homeobox transcription factor 1α (LMX1A) is one of the LIM-homeobox-containing genes that is a critical regulator of growth and differentiation. Recently, LMX1A was shown to be hypermethylated and functioned as a tumor suppressor in cervical cancer, ovarian cancer, and gastric cancer. However, its role in lung cancer has not yet been clarified. In this study, we used public databases, methylation-specific PCR (MSP), reverse transcription PCR (RT-PCR), and bisulfite genomic sequencing to show that LMX1A was downregulated or silenced due to promoter hypermethylation in lung cancers. Treatment of lung cancer cells with the demethylating agent 5-aza-2'-deoxycytidine restored LMX1A expression. In the lung cancer cell lines H23 and H1299, overexpression of LMX1A did not affect cell proliferation but suppressed colony formation and invasion. These suppressive effects were reversed after inhibition of LMX1A expression in an inducible expression system in H23 cells. The quantitative RT-PCR (qRT-PCR) data showed that LMX1A could modulate epithelial mesenchymal transition (EMT) through E-cadherin (CDH1) and fibronectin (FN1). NanoString gene expression analysis revealed that all aberrantly expressed genes were associated with processes related to cancer progression, including angiogenesis, extracellular matrix (ECM) remodeling, EMT, cancer metastasis, and hypoxia-related gene expression. Taken together, these data demonstrated that LMX1A is inactivated through promoter hypermethylation and functions as a tumor suppressor. Furthermore, LMX1A inhibits non-small cell lung cancer (NSCLC) cell invasion partly through modulation of EMT, angiogenesis, and ECM remodeling.

Knockdown of POLDIP2 suppresses tumor growth and invasion capacity and is linked to unfavorable transformation ability and metastatic feature in non-small cell lung cancer.

The main problem in the treatment of non-small cell lung cancer (NSCLC) is metastasis. Epithelial-mesenchymal transition (EMT) is known as the critical signaling in tumor progression, metastasis, and also the drug resistance. In this study, we reported a novel gene Polymerase delta-interacting protein 2 (POLDIP2) was downregulated in NSCLC tissues and first demonstrated that overexpression of POLDIP2 increased the anchorage-independent growth (AIG) and invasiveness of H1299 cells. In addition, we examined that knockdown of POLDIP2 in H1299 and A549 cells reduced tumorigenicity and metastatic capacity in vitro and also in vivo. Moreover, downregulation of the cell proliferation marker cyclin D1 and EMT markers CDH2, Slug, and Twist was showed in H1299 cells by POLDIP2 knockdown, suggesting that the inhibition of malignancy was affected by modulating key genes for tumor growth and invasiveness. Taken together, our study is the first study that demonstrated that POLDIP2 gene was function as an oncogene in NSCLC and implied the oncogenic ability might be through promoting cell proliferation or EMT.

Emetine Synergizes with Cisplatin to Enhance Anti-Cancer Efficacy against Lung Cancer Cells.

Cisplatin is still the primary therapeutic choice for advanced lung cancers without driver mutations. The occurrence of cisplatin resistance is a major clinical problem in lung cancer treatment. The natural extracted agent emetine reportedly has anticancer effects. This study aimed to explore the possible role of emetine in cisplatin resistance. We used cell viability, Western blot, and Wnt reporter assays to show that emetine suppresses proliferation, ß-catenin expression, and Wnt/ß-catenin signaling in non-small cell lung cancer (NSCLC). The synergism of emetine and cisplatin was assessed by constructing isobolograms and calculating combination index (CI) values using the Chou-Talalay method. Emetine effectively synergized with cisplatin to suppress the proliferation of cancer cells. Furthermore, nuclear ß-catenin and cancer stem cell-related markers were upregulated in the cisplatin-resistant subpopulation of CL1-0 cells. Emetine enhanced the anticancer efficacy of cisplatin and synergized with cisplatin in the cisplatin-resistant subpopulation of CL1-0 cells. Taken together, these data suggest that emetine could suppress the growth of NSCLC cells through the Wnt/ß-catenin pathway and contribute to a synergistic effect in combination with cisplatin.

Surviving Sepsis Campaign guidelines for a diver with DCI: case report.

Severe decompression illness (DCI) is an uncommon medical issue affecting divers and results mainly from rapid surfacing using inadequate decompression protocols. Massive gas embolism with central nervous system involvement often leads to a poor prognosis, with permanent residual neurologic defects. Moreover, DCI complicated with multiple organ dysfunction syndrome (MODS) is tremendously rare and difficult to cure, although hyperbaric oxygen (HBO2) therapy following the U.S. Navy Treatment Tables is a consensus. We report a case of severe DCI with profound shock and MODS after an initial treatment with HBO2 therapy using U.S. Navy Treatment Table 6A. Following the Surviving Sepsis Campaign Guidelines, low-dose hydrocortisone was administered. Although this treatment went against recommendation of the U.S. Navy Diving Manual, it resulted in a dramatic clinical improvement. After a second round of HBO2 treatments, the patient was discharged from hospital two weeks after the diving accident.

mRNA markers associated with malignant pleural effusion.

Malignant pleural effusions (MPE) commonly result from malignant tumors and represent advanced-stage cancers. Thus, in clinical practice, early recognition of MPE is valuable. However, the current diagnosis of MPE is based on pleural fluid cytology or histologic analysis of pleural biopsies with a low diagnostic rate. This research aimed to assess the diagnostic ability of eight previously identified Non-Small Cell Lung Cancer (NSCLC)-associated genes for MPE. In the study, eighty-two individuals with pleural effusion were recruited. There were thirty-three patients with MPE and forty-nine patients with benign transudate. mRNA was isolated from the pleural effusion and amplified by Quantitative real-time PCR. The logistic models were further applied to evaluate the diagnostic performance of those genes. Four significant MPE-associated genes were discovered in our study, including Dual-specificity phosphatase 6 (DUSP6), MDM2 proto-oncogene (MDM2), Ring finger protein 4 (RNF4), and WEE1 G2 Checkpoint Kinase (WEE1). Pleural effusion with higher expression levels of MDM2 and WEE1 and lower expression levels of RNF4 and DUSP6 had a higher possibility of being MPE. The four-gene model had an excellent performance distinguishing MPE and benign pleural effusion, especially for pathologically negative effusions. Therefore, the gene combination is a suitable candidate for MPE screening in patients with pleural effusion. We also identified three survival-associated genes, WEE1, Neurofibromin 1 (NF1), and DNA polymerase delta interacting protein 2 (POLDIP2), which could predict the overall survival of patients with MPE.

SOX1 Functions as a Tumor Suppressor by Repressing HES1 in Lung Cancer.

The development of lung cancer is a complex process that involves many genetic and epigenetic changes. Sex-determining region Y (SRY)-box (SOX) genes encode a family of proteins that are involved in the regulation of embryonic development and cell fate determination. SOX1 is hypermethylated in human cancers. However, the role of SOX1 in the development of lung cancer is unclear. We used quantitative methylation-specific polymerase chain reaction (MSP), quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis, and web tools to confirm the frequent epigenetic silencing of SOX1 in lung cancer. Stable overexpression of SOX1 repressed cell proliferation, anchorage-independent growth, and invasion in vitro as well as cancer growth and metastasis in a xenograft mouse model. Knockdown of SOX1 by the withdrawal of doxycycline partly restored the malignant phenotype of inducible SOX1-expressing NSCLC cells. Next, we discovered the potential downstream pathways of SOX1 using RNA-seq analysis and identified HES1 as a direct target of SOX1 using chromatin immunoprecipitation (ChIP)-PCR. Furthermore, we performed phenotypic rescue experiments to prove that overexpression of HES1-FLAG in SOX1-expressing H1299 cells partly reversed the tumor-suppressive effect. Taken together, these data demonstrated that SOX1 acts as a tumor suppressor by directly inhibiting HES1 during the development of NSCLC.

Increased incidence of alcohol use disorder and alcohol-related psychiatric disorders in patients with obstructive sleep apnea: A nationwide population-based cohort study.

BACKGROUND: Obstructive sleep apnea (OSA) and alcohol-related diseases (ARDs), including alcohol use disorder, alcohol-related psychiatric disorders, alcoholic liver disease, alcoholic polyneuropathy alcoholic cardiomyopathy, and alcoholic gastritis, are both highly prevalent conditions. Alcohol consumption is associated with a higher risk of sleep apnea. However, whether OSA increases the risk of ARD has not, as yet, been studied comprehensively. Our study aimed to determine whether OSA increases the subsequent risk of ARD. METHODS: This study utilized the data from Taiwan's National Health Insurance Database between 2000 and 2015. We identified 7722 individuals newly diagnosed with OSA and randomly selected sex-, age-, and index date-matched (1:3) 22,166 controls without OSA, with a total of 29,888 subjects. We used the Fine and Gray's survival analysis to estimate the effects of OSA on ARD. RESULTS: The OSA cohort had an adjusted hazard ratio of subsequent ARDs as 1.486 (95% Confidence Interval: 1.301-1.698), when comparing the cohort without OSA. The Kaplan-Meier analysis showed that the cumulative incidence of ARDs was significantly higher in the OSA cohort than in the controls in the first year of follow-up, till the end of the follow-up. A post-hoc analysis showed that OSA was associated with alcohol use disorder, alcohol-related psychiatric disorders, and alcoholic liver disease, but not alcoholic polyneuropathy, alcoholic cardiomyopathy, and alcoholic gastritis. The use of psychoactive medication, including the sedative-hypnotics, antidepressants or antipsychotics were associated with a lower risk of ARDs. CONCLUSIONS: Our study demonstrates that the OSA patients are at a higher risk of developing ARDs.

Multiple pulmonary nodules in ectopic adrenocorticotropic hormone syndrome: cause or result?

OBJECTIVE: To report a case of invasive pulmonary aspergillosis mimicking lung cancer with lung to lung metastases in ectopic adrenocorticotropic hormone syndrome (EAS). CLINICAL PRESENTATION AND INTERVENTION: A 60-year-old man suffering from hypokalemic alkalosis, hypertension and limbs paralysis was referred to our hospital. EAS caused by malignancy of lung was highly suspected due to multiple pulmonary nodules presenting on chest film and positron emission tomography (PET) images. Video-assisted thoracic surgical biopsy tissue was used to confirm invasive aspergillosis instead of malignancy. Finally, the patient died of opportunistic infection. CONCLUSION: This case showed that although EAS is usually associated with solid tumors, multiple pulmonary nodules secondary to opportunistic infections such as invasive aspergillosis must be kept in mind.

Sonographic septation: a useful diagnostic predictor of complicated parapneumonic effusion.

Sonographic septation is associated with prolonged hospitalization and increased mortality in patients diagnosed with empyema. However, it is unknown whether sonographic septation is associated with complicated parapneumonic effusion (CPPE) or the need for invasive procedures among patients with pneumonia. In this retrospective study, we included 180 patients with non-purulent neutrophilic exudative pleural effusion secondary to pulmonary infections such as pneumonia and lung abscess. We performed univariate and multivariate logistic regression analyses, including baseline clinical characteristics, values from blood samples, and sonographic echogenicity, to identify variables correlated with CPPE and the need for invasive procedures. Seventy of the 180 included patients (38.89%) displayed sonographic septation. Multivariate logistic regression analysis identified that sonographic septation (adjusted OR (AOR)=3.38 (95% CI 1.64 to 6.98), p=0.001) and younger age (AOR=2.63 (95% CI 1.24 to 5.58), p=0.012) were independently associated with CPPE. With regard to treatment strategy, sonographic septation (AOR 9.06 (95% CI 3.71 to 22.11), p<0.001) and total serum protein level (AOR=1.80 (95% CI 1.13 to 2.86), p=0.013) were independently associated with the need for subsequent invasive procedures in patients with CPPE using multivariate logistic regression analysis. Sonographic septation is a useful predictor of CPPE and may imply the need for early invasive procedures.

Long-term atomoxetine-oxybutynin combination use may be beneficial for the prevention of obstructive sleep apnea.

One recent study showed that atomoxetine-oxybutynin combination (AOC) use is effective in reducing obstructive sleep apnea (OSA) severity. We used a nationwide database to examine the association between AOC use and the risk of OSA incidence. This retrospective cohort study used Taiwan's National Health Insurance Research Database between the years 2000 and 2015. The patients who used atomoxetine or oxybutynin were included as an exposed cohort. The exposed and unexposed groups were selected in a ratio of 1:3 with sex, age, and index year matching. We used the multivariate Cox proportional regression model to evaluate the association between AOC use and the risk of an incident diagnosis of OSA. The incidence rates of OSA in the exposed cohort (N = 8940) and the unexposed cohort (N = 26,820), were 21.92 and 22.93 per 100,000 person-years, respectively. The adjusted hazard ratio of oxybutynin use only and AOC with a treatment duration of ≥ 366 days were 0.307 (95% CI 0.204-0.995, P = 0.045) and 0.299 (95% CI 0.102-0.933, P = 0.002), respectively. Long-term atomoxetine-oxybutynin combination therapy may be beneficial to reduce the risk of obstructive sleep apnea. Further studies to examine these mechanisms are warranted.

What could we learn from SARS when facing the mental health issues related to the COVID-19 outbreak? A nationwide cohort study in Taiwan.

There were several studies about the psychiatric and mental health issues related to the severe adult respiratory syndrome (SARS) outbreak in 2003, however, the association between SARS and the overall risk of psychiatric disorders and suicides has, as yet, to be studied in Taiwan. The aim of this study is to examine as to whether SARS is associated with the risk of psychiatric disorders and suicide. A total of 285 patients with SARS and 2850 controls without SARS (1:10) matched for sex, age, insurance premium, comorbidities, residential regions, level of medical care, and index date were selected between February 25 and June 15, 2003 from the Inpatient Database Taiwan's National Health Insurance Research Database. During the 12-year follow-up, in which 79 in the SARS cohort and 340 in the control group developed psychiatric disorders or suicide (4047.41 vs. 1535.32 per 100,000 person-years). Fine and Gray's survival analysis revealed that the SARS cohort was associated with an increased risk of psychiatric disorders and suicide, and the adjusted subdistribution HR (sHR) was 2.805 (95% CI: 2.182-3.605, p < 0.001) for psychiatric disorders and suicide. The SARS cohort was associated with anxiety, depression, sleep disorders, posttraumatic stress disorder/acute stress disorder (PTSD/ASD), and suicide. The sensitivity analysis revealed that the SARS group was associated with anxiety, depression, sleep disorders, PTSD/ASD, and suicide after the individuals with a diagnosis of psychiatric disorders and suicide were excluded within the first year, and with anxiety, depression, and sleep disorders, while those in the first five years were excluded. In conclusion, SARS was associated with the increased risk of psychiatric disorders and suicide.

Association between spinal curvature disorders and injury: a nationwide population-based retrospective cohort study.

OBJECTIVES: Injury is an important issue in public health. Spinal curvature disorders are deformities characterised by excessive curves of the spine. The prevalence of spinal curvature disorders is not low, but its relationship with injury has not been studied. The aim of this study is to investigate whether spinal curvature disorders increase the risk of injury. DESIGN: Population-based retrospective cohort study. SETTING: Using data from the Taiwan National Health Insurance Research Database from 2000 to 2010. PARTICIPANTS AND EXPOSURE: Patients with spinal curvature disorders were selected using codes from the International Classification of Diseases, Ninth Revision, Clinical Modification. A cohort without spinal curvature was randomly frequency-matched to the spinal curvature disorders cohort at a ratio of 2:1 according to age, sex and index year. PRIMARY OUTCOME MEASURES: The risk of injury was analysed using Cox's proportional hazards regression models adjusting for age, sex, comorbidities, urbanisation level and socioeconomic status. RESULTS: A total of 20 566 patients with spinal curvature disorders and 41 132 controls were enrolled in this study. The risk of injury was 2.209 times higher (95% CI 2.118 to 2.303) in patients with spinal curvature disorders than in the control group. The spinal curvature disorders cohort exhibited higher risk of developing injury compared with the control group, regardless of age, sex, comorbidities, urbanisation level and subgroup of spinal curvature disorders. Based on the subgroup analysis, the spinal curvature disorders cohort had higher risks of unintentional injury and injury diagnoses such as fracture, dislocation, open wound, superficial injury/contusion, crushing and injury to nerves and spinal cord compared with the control cohort. CONCLUSIONS: Patients with spinal curvature disorders have a significantly higher risk of developing injury than patients without spinal curvature disorders. Aggressive detection and management of spinal curvature disorders may be beneficial for injury prevention.

Obstructive Sleep Apnea in Children and Adolescents and the Risk of Major Adverse Cardiovascular Events: A Nationwide Cohort Study in Taiwan.

STUDY OBJECTIVES: This study has investigated the risk of major adverse cardiovascular events (MACEs), including acute myocardial infarction, coronary artery disease, peripheral artery disease, and acute stroke, among children and adolescents (age younger than 20 years) with obstructive sleep apnea (OSA). METHODS: In this study, the population-based National Health Insurance Research Database of Taiwan was used to identify patients in whom OSA had been first diagnosed between 2000 and 2015. Children and adolescents with OSA (n = 6,535) were included with 1:3 ratio by age, sex, and index year of control participants without OSA (n = 19,605). The Cox proportional regression model was used to evaluate the risk of MACEs in this cohort study. RESULTS: After a 15-year follow-up, the incidence rate of MACEs was higher in the OSA cohort when compared with the non-OSA control cohort (15.97 and 8.20 per 100,000 person-years, respectively). After adjusting for covariates, the risk of MACEs among children and adolescents with OSA was still significantly higher (hazard ratio = 2.050; 95% confidence interval = 1.312-3.107; P = .010). No MACEs were found in the children and adolescents with OSA who received continuous airway positive pressure treatment or pharyngeal surgery. CONCLUSIONS: This study found a significantly higher risk of MACEs in children and adolescents with OSA. These findings strongly suggest that clinicians should provide careful follow-up and medical treatment for children and adolescents with OSA.

Non-Apnea Sleep Disorder associates with increased risk of incident heart failure-A nationwide population-based cohort study.

PURPOSE: Non-apnea sleep disorder (NASD) increases the risk of cardiovascular events, such as hypertension and ischemic heart disease (IHD). Patients with heart failure (HF) are at higher risk for sleep disorder; however, there is no documentation on NASD's association with HF to date. Therefore, our study aimed to determine whether NASD increases the risk of incident HF. MATERIALS AND METHODS: Using the outpatient and inpatient data from Taiwan's Longitudinal Health Insurance Database, we conducted a nationwide cohort study of patients with a first-time diagnosis of NASD in the year 2000 and followed up the risk of incident heart failure until December 31, 2013. We calculated risks and incidence ratios of HF for patients with NASD compared with the general population. The cumulative incidence of NASD and the subsequent risk of HF are assessed by the Kaplan-Meier method and Cox regression using a matched comparison cohort of HF patients without NASD. RESULTS: The NASD cohort had an adjusted hazard ratio (HR) of incident HF 19.7% higher than that of the cohort without NASD (95% CI = 1.130-1.270; p<0.001). In the NASD population, the mean interval to HF in males and females were 5.00±3.69 years and 5.00±3.66 years, respectively. The Kaplan-Meier analysis indicated that after the seventh year, the incidence of HF was higher in the NASD cohort than in the control cohort till the end of the follow up. CONCLUSIONS: Our study demonstrates that NASD patients are associated with a higher risk of incident HF.

Risk of psychiatric disorders in pulmonary embolism: a nationwide cohort study.

This study aims to investigate the association between pulmonary embolism (PE) and the risk of psychiatric disorders. A total of 21,916 patients aged ≥20 years with PE between January 1, 2000, and December 31, 2015, were selected from the National Health Insurance Research Database of Taiwan, along with 65,748 (1:3) controls matched for sex and age. Cox regression model revealed the crude HR was 1.539 (95% CI 1.481 to 1.599; p<0.001), and after adjusting all the covariates, the adjusted HR was 1.704 (95% CI 1.435 to 1.991, p<0.001), for the risk of psychiatric disorders in the PE cohort. PE was associated with the overall psychiatric disorders, dementia, anxiety, depression, and sleep disorders, after the exclusion of the psychiatric diagnoses in the first year. PE was associated with the overall psychiatric disorders, dementia, anxiety, and depression, after the exclusion of the psychiatric diagnoses in the first 5 years. The patients with PE were associated with psychiatric disorders. This finding could serve as a reminder to the physicians to be more watchful and aware in the long-term follow-up of patients with PE for their care and potential mental health problems.

Non-Apnea Sleep Disorder Increases the Risk of Subsequent Female Infertility-A Nationwide Population-Based Cohort Study.

Study Objectives: Non-apnea sleep disorder (NASD) increases the risk of hypertension, type 2 diabetes mellitus, chronic kidney disease, cardiovascular disease, and stroke. However, the risk and the time interval of NASD to female infertility has not been thoroughly understood. Our study aimed to determine whether NASD increases the subsequent risk of female infertility. Methods: This study utilized outpatient and inpatient data from the Longitudinal Health Insurance Database between 2000 and 2010 in Taiwan. We enrolled 50,154 females aged 20 to 45 years old and diagnosed with NASD as outpatients ≥2 times or hospitalized, 16,718 of them who matched our criteria were assigned to the study group. For each NASD patient, two comparison patients were frequency matched by age (each 5-year span), index date, and comorbidities as the control cohort with a total of 33,436 patients. We conducted Cox proportional hazard regression analysis to estimate the effects of NASD on female infertility. Results: The NASD cohort had an adjusted hazard ratio (HR) of subsequent female infertility of 3.718-fold higher than that of the cohort without sleep disorders. In the stratified age group, NASD had the highest impact on 26-30 years old, with an adjusted HR of 5.146 followed by 31-35 years old (adjusted HR = 3.356). The Kaplan-Meier analysis also showed that in the sixth year of follow-up, the incidence of female infertility was higher in the NASD cohort than in the general population cohort till the end of the follow-up. Conclusions: Our study demonstrates that NASD patients are at a higher risk of developing female infertility.

Increased Risk of Psychiatric Disorders in Allergic Diseases: A Nationwide, Population-Based, Cohort Study.

BACKGROUND/OBJECTIVE: Allergic diseases, such as bronchial asthma, allergic rhinitis, atopic dermatitis, and psychiatric disorders, are major health issues. There have been reports that allergic diseases were associated with depression or anxiety disorders. This study aimed to investigate the association between these allergic diseases and the risk of developing overall psychiatric disorders in patients from Taiwan. METHODS: This cohort study used the database of the Taiwan National Health Insurance Program. A total of 186,588 enrolled patients, with 46,647 study subjects who had suffered from allergic diseases, and 139,941 controls matched for sex and age, from the Longitudinal Health Insurance Dataset of 2000-2015, were selected from a sub-dataset of the National Health Insurance Research Database. Fine and Gray's competing risk model analysis was used to explore the hazard ratio (HR), and 95% confidence interval, for the risk of allergic diseases being associated with the risk of developing psychiatric disorders during the 15 years of follow-up. RESULTS: Of the study subjects, 5,038 (10.8%) developed psychiatric disorders when compared to 9,376 (6.7%) in the control group, with significant difference (p < 0.001). Fine and Gray's competing risk model analysis revealed that the adjusted HR was 1.659 (95% CI = 1.602-1.717, p < 0.001). In this study, we found that the groups of atopic dermatitis alone and the allergic rhinitis + atopic dermatitis were associated with a lower risk of psychiatric disorders, but all the other four groups, such as bronchial asthma alone, allergic rhinitis alone, bronchial asthma + allergic rhinitis, bronchial asthma + atopic dermatitis, and the combination of all these three allergic diseases, were associated with a higher risk of psychiatric disorders. CONCLUSION: Allergic diseases are therefore associated with a 1.66-fold increased hazard of psychiatric disorders in Taiwan.

Risk of dementia after charcoal-burning suicide attempts: a nationwide cohort study in Taiwan.

This study aimed to investigate the association between charcoal-burning suicide attempts and the risk of developing dementia. A nationwide, matched cohort, population-based study enrolled a total of 4103 patients with newly diagnosed charcoal-burning suicide attempts, between 2000 and 2010, which were selected from the National Health Insurance Research Database of Taiwan, along with 12,309 controls matched for sex and age. After adjusting for confounding factors, Fine and Gray's competing risk analysis was used to compare the risk of developing dementia during the 10-year follow-up period. Of the enrolled patients (n=16,412), dementia developed in 303 (1.85%), including 2.56% in the study group (105 in 4103) and 1.61% (198 in 12,309) in the control group. The Fine and Gray's survival analysis revealed that the patients with charcoal-burning suicide attempts were likely to develop dementia, with a crude HR of 5.170 (95% CI 4.022 to 6.644, p<0.001). After adjusting for age, sex, comorbidity, geographic area and urbanization level of residence, and monthly insured premium, the adjusted HR was 4.220 (95% CI 3.188 to 5.586, p<0.001). Suicide attempts were associated with an increased risk of degenerative dementia in this study. Patients with charcoal-burning suicide attempts had a fourfold risk of dementia than the control group.

Short-term starvation with a near-fatal asthma attack induced ketoacidosis in a nondiabetic pregnant woman: A case report.

Life-threatening refractory metabolic acidosis due to starvation ketoacidosis is rarely reported, even among nondiabetic pregnant women, and may be overlooked. Furthermore, stressful situations may increase the acidosis severity.In the present case, a nondiabetic multiparous woman was admitted for a near-fatal asthma attack and vomiting during the third trimester of pregnancy. She was intubated and rapidly developed high anion gap metabolic acidosis. We diagnosed the patient with starvation ketoacidosis based on vomiting with concomitant periods of stress during pregnancy and the absence of other causes of high anion gap metabolic acidosis. She responded poorly to standard treatment, although the ketoacidosis and asthma promptly resolved after an emergency caesarean section. The patient and her baby were safely discharged.Short-term starvation, if it occurs during periods of stress and medication, can result in life-threatening ketoacidosis, even among nondiabetic women during the third trimester of pregnancy. Awareness of this condition may facilitate prompt recognition and proactive treatment for dietary and stress control, and emergent interventions may also improve outcomes.