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Background Chest pain is the most common symptom of aortic dissection (AD), but it is often confused with other prevalent cardiopulmonary diseases. We aimed to develop deep-learning models (DLMs) with ECG and CXR features to detect AD and evaluate their performance. Methods This study included 43,473 patients in the emergency department (ED) between July 2012 and December 2019 for retrospective DLM development. A development cohort including 49,071 ED records (120 AD-type A and 64 AD-type B) was used to train DLMs for ECG and CXR, and 9,904 independent ED records (40 AD-type A and 34 AD-type B) were used to validate DLM performance. Human–machine competitions of ECG and CXR were conducted. Patient characteristics and laboratory results were used to enhance the diagnostic accuracy. The DLM-enabled AD diagnostic process was prospectively evaluated in 25,885 ED visits. Results The AUCs of the ECG and CXR models were 0.918 and 0.857 for detecting AD in a human–machine competition, respectively, which were better than those of the participating physicians. In the validation cohort, the AUCs of the integrated model were 0.882, 0.960, and 0.813 in all AD, AD-type A, and AD-type B patients, respectively, with a sensitivity of 100.0% and a specificity of 81.7% for AD-type A. In patients with chest pain and D-dimer tests, the DLM could predict more precisely, achieving a positive predictive value of 62.5% in the prospective evaluation. Conclusions DLMs may serve as decision-supporting tools for AD identification and facilitate differential diagnosis in patients with acute chest pain.

Background: In the past decade, Tri-Service General Hospital has trained many actors-background standardized patients (SPs). However, we also have recruited some nonactor SPs since 2010. Reviewing the literature, the reliability of SPs with or without actor background would be the impact factor on high-stakes OSCE has not been well studied. Aim: The purpose of this retrospective observation is to clarify whether a SP with or without a professional actor background will affect the performances of the examination when participating in the Taiwan high-stakes objective structured clinical examination (OSCE). The result will be the policy for selecting which kind of SPs to participate in the high-stack OSCE in our hospital. Methods: In this retrospective observation, we analyzed 74 actor background SPs (A-SPs), and 70 no actor background SPs (NA-SPs) who have participated in each spring test of 2015–2017 Taiwan high-stakes OSCE. The data of SPs performance have come from two parts: one is from the examinee with the global rating of the SPs performance and the other is from the examiner with eight-item checklist for the SPs performance. The scoring of both examinee and examiner is a five-point Likert scale. Results: The results show that there is no significant difference in SPs performance from the examinee scoring in the subsequent 3 years, stable and satisfactory, and let examinees feel like real patients. The scores from examiners also showed that two groups of SPs performed equally well without significant differences. Their performance is reliable and consistent, simulating to be a real patient in both groups. However, only one interest finding, when compared to the different age subdivision of SPs, showed the aged subgroup of A-SPs and NA-SPs with the significant difference in the item of reliability and consistent (4.67 ± 0.53 vs. 4.41 ± 0.50, P < 0.05), the possible reason is related to the less-experienced associate with mild memory decline in aged NA-SPs.Conclusions: Our observation gives the essential information, that the well-trained and experienced SP are necessary for participating in the high-stakes OSCE examination, even without the background of the actor. What we need is a professional SP who not only has excellent professionalism but also has a good personality literacy to engage in his/her work.

Objectives The choice of optimal antithrombotic therapy in atrial fibrillation (AF) patients with acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI) remains controversial. The aim of this longitudinal cohort study is to investigate the prescribing pattern of antithrombotic regimen in different cohorts and its subsequent impact. Setting and design Longitudinal data from the Tri-Service General Hospital-Coronary Heart Disease (TSGH-CHD) registry, between January 2016 and August 2018 was screened. Participants and method Patients with prior history of nonvalvular AF, who had ACS presentation or underwent PCI were selected, and these patients were divided into cohort 1 and cohort 2, according to the index date of antithrombotic prescription before and after the PIONEER AF-PCI study. Primary and secondary outcomes The primary safety endpoints were composites of major bleeding and/or clinically relevant non-major bleeding. The secondary efficacy endpoints included the occurrence of all-cause mortality, stroke/systemic embolization, nonfatal myocardial infarction (MI), and >30-days coronary revascularization. Results A total of 121 patients were included into analysis (cohort 1=35; cohort 2=86). Comparing with cohort 1, the prescription rate of triple antithrombotic therapy (TAT) increased from 17.1 to 38.4%, especially the regimen with dual antiplatelet therapy (DAPT) plus low-dose non-vitamin-K dependent oral anticoagulation (NOAC). However, the prescription rate of dual antithrombotic therapy (DAT) decreased (14.3–10.5%), as well as the prescription rate of DAPT (68.6–51.2%). These changes of antithrombotic prescription across different cohorts were not associated with risk of adverse safety (HR= 0.87; 95% CI, 0.42-1.80, p=0.710) and efficacy outcomes (HR=0.96; 95% CI, 0.40-2.32, p=0.930). Conclusions Entering the NOAC era, the prescription of TAT increased alongside the decrease in DAT. As the prescription rate of DAPT without anticoagulation remained high, future efforts are mandatory to improve the implementation of guidelines and clinical practice.

Background: glycated hemoglobin (HbA1c) provides information on diabetes mellitus (DM) management. Electrocardiography (ECG) is a noninvasive test of cardiac activity that has been determined to be related to DM and its complications. This study developed a deep learning model (DLM) to estimate HbA1c via ECG. Methods: there were 104,823 ECGs with corresponding HbA1c or fasting glucose which were utilized to train a DLM for calculating ECG-HbA1c. Next, 1539 cases from outpatient departments and health examination centers provided 2190 ECGs for initial validation, and another 3293 cases with their first ECGs were employed to analyze its contributions to DM management. The primary analysis was used to distinguish patients with and without mild to severe DM, and the secondary analysis was to explore the predictive value of ECG-HbA1c for future complications, which included all-cause mortality, new-onset chronic kidney disease (CKD), and new-onset heart failure (HF). Results: we used a gender/age-matching strategy to train a DLM to achieve the best AUCs of 0.8255 with a sensitivity of 71.9% and specificity of 77.7% in a follow-up cohort with correlation of 0.496 and mean absolute errors of 1.230. The stratified analysis shows that DM presented in patients with fewer comorbidities was significantly more likely to be detected by ECG-HbA1c. Patients with higher ECG-HbA1c under the same Lab-HbA1c exhibited worse physical conditions. Of interest, ECG-HbA1c may contribute to the mortality (gender/age adjusted hazard ratio (HR): 1.53, 95% conference interval (CI): 1.08–2.17), new-onset CKD (HR: 1.56, 95% CI: 1.30–1.87), and new-onset HF (HR: 1.51, 95% CI: 1.13–2.01) independently of Lab-HbA1c. An additional impact of ECG-HbA1c on the risk of all-cause mortality (C-index: 0.831 to 0.835, p &lt, 0.05), new-onset CKD (C-index: 0.735 to 0.745, p &lt, 0.01), and new-onset HF (C-index: 0.793 to 0.796, p &lt, 0.05) were observed in full adjustment models. Conclusion: the ECG-HbA1c could be considered as a novel biomarker for screening DM and predicting the progression of DM and its complications.

Diabetes is a common comorbidity in patients hospitalized for acute heart failure (AHF), but the relationship between admission glucose level, glycemic gap, and in-hospital mortality in patients with both conditions has not been investigated thoroughly. Clinical data for admission glucose, glycemic gap and in-hospital death in 425 diabetic patients hospitalized because of AHF were collected retrospectively. Glycemic gap was calculated as the A1c-derived average glucose subtracted from the admission plasma glucose level. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff value for glycemic gap to predict all-cause mortality. Patients with glycemic gap levels >43 mg/dL had higher rates of all-cause death (adjusted hazard ratio, 7.225, 95% confidence interval, 1.355–38.520) than those with glycemic gap levels ≤43 mg/dL. The B-type natriuretic peptide levels incorporated with glycemic gap could increase the predictive capacity for in-hospital mortality and increase the area under the ROC from 0.764 to 0.805 (net reclassification improvement = 9.9%, p

Background: Taiwan is located in a subtropical area where there are approximately 50 kinds of land snakes and six principal kinds of venous snakes. Snakebite envenomation is not an uncommon issue in Taiwan. We design a study to obtain an understanding of the characteristics of snakebites and snakebite patients in a medical center in northern Taiwan. Materials and Methods: This was a retrospective medical records study of an 8-year period. We used the key word “snake” to search the emergency department (ED) diagnosis of all patients and then used antivenom management codes to select patients for inclusion. The species of snake involved, time and site of the bite, geographic data of the patients and patient outcomes were recorded. Results: In total, there were 125 snakebite patients (male 70%, female 30%). The snakes involved were Protobothrops mucrosquamatus (50%), followed by Trimeresurus stejnegeri (7%). The feet and ankles were the most frequently bitten areas (42.4%). The peak months were July and October. The average ED stasis time was 2 hours and 45 minutes, and 65.6% of snakebite patients received antivenom. In patients bitten by P. mucrosquamatus, there was a high surgical rate, 23.8% higher than those reported in other studies. No mortalities or side effects of antivenom were reported in these patients. Conclusion: We propose a clinical flow chart for physicians who are treating patients bitten by P. mucrosquamatus. Snakebites, especially those inflicted by P. mucrosquamatus, induce severe soft tissue swelling, which can mimic compartment syndrome. Antivenom for P. mucrosquamatus is the first and only choice of treatment. The amount of antivenom needs to match the clinical symptoms. Patients bitten by P. mucrosquamatus may need longer observation times than patients bitten by other species of snakes, in addition to toxicologist consultations, sonographic examinations, and measurement of the objective compartment pressure before surgery.

The impact of the coronavirus disease 2019 (COVID-19) pandemic on health-care quality in the emergency department (ED) in countries with a low risk is unclear. This study aimed to explore the effects of the COVID-19 pandemic on ED loading, quality of care, and patient prognosis. Data were retrospectively collected from 1 January 2018 to 30 September 2020 at the ED of Tri-service general hospital. Analyses included day-based ED loading, quality of care, and patient prognosis. Data on triage assessment, physiological states, disease history, and results of laboratory tests were collected and analyzed. The number of daily visits significantly decreased after the pandemic, leading to a reduction in the time to examination. Admitted patients benefitted from the pandemic with a reduction of 0.80 h in the length of stay in the ED, faster discharge without death, and reduced re-admission. However, non-admitted visits with chest pain increased the risk of mortality after the pandemic. In conclusion, the COVID-19 pandemic led to a significant reduction in low-acuity ED visits and improved prognoses for hospitalized patients. However, clinicians should be alert about patients with chest pain due to their increased risk of mortality in subsequent admission.

The incidence of acute compartment syndrome (ACS) following snakebite envenomation may be seriously overestimated in Taiwan. Snakebite-induced ACS is difficult to determine solely by clinical examination. Snakebite patients previously underwent surgical intervention based on speculation and general clinical examinations suggesting ACS presentations instead of direct intracompartmental pressure (IP) measurement prior to fasciotomy. Point-of-care ultrasound (POCUS) is a relatively widely available noninvasive tool. This study aimed to evaluate snakebite-envenomated patients for the presence of subcutaneous edema and diastolic retrograde arterial flow (DRAF).Snakebite patients were prospectively recruited between 2017 and 2019. All patients were examined with POCUS to locate edema and directly visualize and measure the arterial flow in the compressed artery. The presence of DRAF in the compressed artery is suggestive of ACS development because when compartment space restriction occurs, increased retrograde arterial flow is observed in the artery.Twenty-seven snakebite patients were analyzed. Seventeen patients (63%) were bitten by Crotalinae snakes, seven (26%) by Colubridae, one (4%) by Elapidae, and two (7%) had unidentified snakebites. All Crotalinae bit patients received antivenom, had subcutaneous edema and lacked DRAF in a POCUS examination series.POCUS facilitates clinical decisions for snakebite envenomation. We also highlighted that the anatomic site of the snakebite is an important factor affecting the prognosis of the wounds. There were limitations of this study, including a small number of patients and no comparison with the generally accepted invasive evaluation for ACS.We are unable to state that POCUS is a valid surrogate measurement of ACS from this study but see this as a starting point to develop further research in this area. Further study will be needed to better define the utility of POCUS in patients envenomated by snakes throughout the world.

The prevalence of mitral valve prolapse (MVP) among middle- and older-aged individuals is estimated to be 2–4% in Western countries. However, few studies have been conducted among Asian individuals and young adults. This study included a sample of 2442 consecutive military adults aged 18–39 years in Hualien, Taiwan. MVP was defined as displacement of the anterior or posterior leaflet of the mitral valve to the mid portion of the annular hinge point > 2 mm in the parasternal long-axis view of echocardiography. Cardiac chamber size and wall thickness were measured based on the latest criteria of the American Society of Echocardiography. The clinical features of participants with MVP and those without MVP were compared using a two-sample t test, and the cardiac structures were compared using analysis of covariance with adjustment for body surface area (BSA). Eighty-two participants were diagnosed with MVP, and the prevalence was 3.36% in the overall population. Compared with those without MVP, participants with MVP had a lower body mass index (kg/m2) (24.89 ± 3.70 vs. 23.91 ± 3.45, p = 0.02) and higher prevalence of somatic symptoms related to exercise (11.0% vs. 4.9%, p = 0.02) and systolic click in auscultation (18.3% vs. 0.6%, p

Statins constitute the mainstay treatment for atherosclerotic cardiovascular disease, which is associated with the risk of new-onset diabetes mellitus (NODM). However, the effects of individual statins on the risk of NODM remain unclear. We recruited 48,941 patients taking one of the three interested statins in a tertiary hospital between 2006 and 2018. Among them, 8337 non-diabetic patients taking moderate-intensity statins (2 mg/day pitavastatin, 10 mg/day atorvastatin, and 10 mg/day rosuvastatin) were included. The pitavastatin group had a higher probability of being NODM-free than the atorvastatin and rosuvastatin groups during the 4-year follow-up (log-rank test: p = 0.038). A subgroup analysis revealed that rosuvastatin had a significantly higher risk of NODM than pitavastatin among patients with coronary artery disease (CAD) (adjusted HR [aHR], 1.47, 95% confidence interval [CI], 1.05&ndash, 2.05, p = 0.025), hypertension (aHR, 1.26, 95% CI, 1.00&ndash, 1.59, p = 0.047), or chronic obstructive pulmonary disease (COPD) (aHR, 1.74, 95% CI, 1.02&ndash, 2.94, p = 0.04). We concluded that compared with rosuvastatin, reduced diabetogenic effects of pitavastatin were observed among patients treated with moderate-intensity statin who had hypertension, COPD, or CAD. Additional studies are required to prove the effects of different statins on the risk of NODM.

BackgroundThe initial detection and diagnosis of ST-segment or non-ST-segment elevation myocardial infarction (STEMI or NSTEMI) definitely rely on a 12-lead electrocardiogram (ECG). Delay or misdiagnosis is not unusual by subjective interpretation. Our aim is to develop a DLM as a diagnostic support tool to detect MI based on a 12-lead ECG and to evaluate the performance of this model.MethodsThis study included 1,051 ECGs from 737 coronary angiography (CAG)-validated STEMI patients, 697 ECGs from 287 CAG-validated NSTEMI patients, and 140,336 not-MI ECGs from 76,775 patients at emergency departments. DLM was trained and validated for the performance using 80% and 20% of the ECGs, respectively. A human-machine competition was conducted. The area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were used to evaluate the performance of DLM and experts. STEMI versus not-STEMI, and MI versus not-MI were evaluated by DLM.ResultsThe AUCs of DLM for identifying STEMI and MI were 0.976 and 0.944 in the human-machine competition, respectively, which were significantly better than those of our best clinicians. In the real world setting, DLM presented with AUC of 0.995/0.916 with corresponding sensitivities of 96.9%/77.0%, and specificities of 96.2%/92.9% in the identification of STEMI and MI, respectively. Furthermore, DLM demonstrated sufficient diagnostic capacity for STEMI without the aid of troponin I (TnI) (AUC= 0.996) with corresponding sensitivity and specificity of 98.4% and 96.9%. The AUC of combined DLM and the first recorded TnI for the detection of NSTEMI were increased to 0.978 with corresponding sensitivity and specificity of 91.6% and 96.7%, which was better than that of DLM (0.877) or TnI (0.949) alone. ConclusionsDLM may serve as a diagnostic decision tool to assist intensive or emergency medical system-based networks and frontline physicians in identifying STEMI and NSTEMI in a timely and precise manner to prevent delay or misdiagnosis, and thereby to facilitate subsequent reperfusion therapy.

Purpose: To investigate the association of preexisting hypertension at admission with the mortality in patients with systolic heart failure (HF). Method: We prospectively investigated the association of preexisting hypertension with the mortality among 1351 patients with HF in Taiwan during an average 12 months (range: 8 months–18 months) follow-up period. A multivariate cox regression analysis for the overall cohort and a subgroup analysis by age were performed. Results: After adjustment for all potential risk factors, the associations of preexisting hypertension with cardiovascular mortality were significantly reduced in the overall cohort and those aged less than 65 years (hazard ratios (HR): 0.53, 95% confidence intervals (CI): 0.33–0.84, and 0.28, 95% CI: 0.11–0.67, respectively). However, the associations with all-cause mortality were not significantly different in these two groups (HR: 0.77, 95% CI: 0.54–1.09, and 0.59, 95% CI: 0.32–1.07, respectively). Furthermore, the associations were all nonsignificant in the patients aged older than 65 years. Conclusion: Preexisting hypertension have an inverse association with cardiovascular mortality in the Asian patients with systolic HF, particularly for those with younger ages. Keywords: Reverse epidemiology, Pre-existing hypertension, Heart failure

BACKGROUND Atopic dermatitis (AD) is associated with systemic inflammation and may have a similar pathogenesis as obstructive sleep apnea (OSA). However, to date, studies on the association between AD and OSA are limited. OBJECTIVES This study evaluated the association between OSA and AD in children in a large-scale, population-based cohort. METHODS A total of approximately 120 736 children (

Objective: To investigate the 12-lead surface electrocardiographic (ECG) findings in young male patients with left primary spontaneous pneumothorax (PSP) estimated by the Collins equation. Methods: From 2003 through 2008, 60 young male patients who had left PSP and 61 age-matched unaffected males were included for 12-lead ECG analyses. The PSP size was estimated by the Collins equation. Those with left PSP were divided into two groups: 1) large PSP ≥30% (n = 37), and 2) small PSP

// Yu-Hsiang Chiu 1 , Chi-Hsiang Chung 2 , Kuen-Tze Lin 3 , Chin-Sheng Lin 4 , Jia-Hong Chen 5 , Hsiang-Cheng Chen 1 , Ren-Yeong Huang 6 , Chi-Tsung Wu 7 , Feng-Cheng Liu 1 and Wu-Chien Chien 2,8 1 Department of Internal Medicine, Division of Rheumatology/Immunology/Allergies, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan 2 School of Public Health, National Defense Medical Center, Taipei, Taiwan 3 Department of Radiation Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan 4 Department of Internal Medicine, Division of Cardiology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan 5 Department of Internal Medicine, Division of Hematology/Oncology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan 6 Department of Periodontology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan 7 Department of Oral and Maxillofacial Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan 8 Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan Correspondence to: Wu-Chien Chien, email: // Feng-Cheng Liu, email: // Keywords : Sjogren syndrome, non-Hodgkin’s lymphoma, diffuse large B-cell lymphoma, immunosuppressive agents, lip biopsy Received : August 04, 2016 Accepted : January 23, 2017 Published : February 04, 2017 Abstract Sjogren syndrome (SS) is commonly known to be correlated with lymphoma. This study included 16,396 individuals in the SS cohort and 65,584 individuals in the non-SS cohort, all of whom were enrolled in the Taiwan National Health Insurance database between 2000 and 2010. We evaluated the risk factors of non-Hodgkin’s lymphoma (NHL) in the primary SS cohort by applying a Cox multivariable proportional-hazards model. We increased the correlation of patients with SS and NHL, with an adjusted HR of 4.314 (95% CI 2.784 – 6.685). Of the 16,396 SS patients, 66 individuals had salivary gland slices without NHL development, while the other 16,330 individuals that did not have salivary gland slices revealed 30 individuals that developed NHL. Of the 16,396 SS patients, 128 individuals underwent immunomodulator agent therapy (including hydroxychloroquine, azathioprine, cyclosporine, methotrexate, and rituximab) without NHL development. None of the 30 individuals that developed NHL from SS received immunomodulator agents. We found that patients with SS were at an increased risk of developing NHL, with the most common NHL subgroup being diffused large B-cell lymphoma. SS patients who were candidates for salivary gland slices or immunomodulator agents were associated with a lower risk of developing lymphoma over time. We recommend that patients at a higher risk upon diagnosis of SS receive close follow-up and aggressive treatment.

Anemia defined as reduced hemoglobin levels of red blood cells may carry less oxygen to skeletal muscle and impair physical performance. Previous studies have shown that exercise intolerance was related to moderate or severe anemia, however, the relationship to mild anemia was unknown. We investigated the cross-sectional association of mild anemia defined as a hemoglobin level of 10.0–13.9 g/dL with physical fitness in 3,666 military young males in Taiwan in 2014. Aerobic fitness was evaluated by 3000-meter run test, and anaerobic fitness was evaluated by 2-minute sit-ups and 2-minute push-ups, respectively. Multiple logistic regressions for the best 10% and the worst 10% performers were used to determine the relationship. There were 343 mild anemic males in whom 47.8% were microcytic anemia and 3,323 non-anemic males for the analysis. The multiple logistic regression shows that as compared with non-anemic males, mild anemic males were more likely to be the worst 10% performers in the 3000-meter run test (odds ratios (OR) and 95% confidence intervals: 1.47, 1.01–2.14) after adjusting for age, service specialty, body mass index, waist size, mean blood pressure, unhealthy behaviors, lipid profiles, and exercise frequency. On the contrary, mild anemic males had higher possibility to be the best 10% performers in the 2-minute push-ups test (OR: 1.48, 1.08–2.04). However, there was no association between mild anemia and 2-minute sit-ups. Our findings suggest that unspecified mild anemia might be associated with lower cardiorespiratory fitness but not with anaerobic fitness in physically active military males.

PurposeThis study evaluated the association between ischaemic stroke (IS) and heart failure (HF) in the absence of atrial fibrillation (AF) or atrial flutter (AFL) using a population-based nation-wide cohort database.MethodNewly diagnosed patients with HF without previous stroke and acute myocardial infarction (AMI) were enrolled. Based on the propensity scores matching age, sex and all comorbidities, our studies comprised 12 179 patients with HF and 12 179 patients without HF. Cox proportion hazard regression models and competing-risk regression models were used to evaluate the risk of IS among patients with HF without AF or AFL.ResultsIn the multivariable analysis, older age (adjusted HR (95% CI)=1.05 (1.04 to 1.05)), male sex (adjusted HR (95% CI)=1.36 (1.24 to 1.50)), diabetes (adjusted HR (95% CI)=2.22 (1.97 to 2.49)) and hypertension (adjusted HR (95% CI)=1.60 (1.41 to 1.82)) were markedly associated with IS in patients with HF. The HF group had a markedly higher risk of IS than did the non-HF group (subdistribution HR (SHR)=1.51, 95% CI: 1.37 to 1.66) and AMI (SHR=3.40, 95% CI: 2.71 to 4.28). Additionally, according to the Kaplan-Meier analysis, patients with HF were at a significantly higher risk of cumulative incidence of IS and AMI than did patients with non-HF (p value of log-rank test ConclusionThis study indicated that HF is a strong independent risk factor for IS, even in the absence of AF or AFL. Clinical physicians should investigate IS through routine screening and careful monitoring of patients with HF.

Background Cardiovascular diseases (CVDs) and aortic aneurysms (AAs) share several clinical risk factors. However, the potential effects on future CVDs of surgical treatments involving the open surgical repair (OSR) of AAs are unknown. We hypothesize that the OSR of AAs is associated with subsequent CVDs. Methods The data for this nationwide population-based retrospective cohort study were obtained from the National Health Insurance Research Database in Taiwan. The outcome assessed in this study was the cumulative incidence of CVDs in patients with AAs during a 14-year follow-up period, which was further stratified according to those who underwent OSR, endovascular aneurysm repair (EVAR), and nonsurgical treatment (NST). Results Our analysis included 11,764 patients with AAs, of whom 2,524 received surgery and 2,524 were propensity score-matched controls. Compared to the controls, patients who received OSR exhibited a significantly decreased incidence of CVD development [adjusted hazard ratio (HR) = 0.89,p = 0.006]. Furthermore, compared to patients who received NST, patients who received OSR had a significantly lower incidence of subsequent acute myocardial infarction (adjusted HR = 0.793, p = 0.037). Conclusions Compared to NST, OSR of AAs could be associated with a lower incidence of subsequent CVDs.

Coronary artery disease combined sepsis associated myocardial ischemia resulting in diffuse ST elevation on electrocardiogram has rarely been reported. We reported a rare case of diffuse ST elevation precipitated by septic shock and preexisting severe atherosclerosis heart disease. In clinical scenario, it is imperative for physicians to be aware of non-ischemic ST elevation etiologies and avoid inappropriate activation of the percutaneous coronary intervention (PCI) protocol, while not missing ST elevation myocardial infarction.

Cardiovascular disease is one of the leading causes of death and disability in the world. Atherosclerosis, characterized by lipid accumulation and chronic inflammation in the vessel wall, is the main feature of cardiovascular disease. Although the amounts of fruits and vegetables present in the diets vary by country, diets, worldwide, contain large amounts of spices; this may have positive or negative effects on the initiation and development of atherosclerosis. In this review, we focused on the potential protective effects of specific nutrients from spices, such as pepper, ginger, garlic, onion, cinnamon and chili, in atherosclerosis and atherosclerotic cardiovascular disease. The mechanisms, epidemiological analysis, and clinical studies focusing on a variety of spices are covered in this review. Based on the integrated information, we aimed to raise specific recommendations for people with different dietary styles for the prevention of atherosclerotic cardiovascular disease through dietary habit adjustments.

Objective: Atrial fibrillation (AF) is the most common form of sustained arrhythmia. Several molecular pathways associated with the pathogenesis of AF also participate in the initiation and progression of aortic aneurysm (AA). In this study, we aimed to evaluate potential associations between AA and AF. Patients and Methods: The data for this nationwide population-based retrospective cohort study were obtained from Taiwan’s National Health Insurance Research Database (NHIRD). All medical conditions for each case and the controls were categorized using the 9th revision of the International Classification of Diseases (ICD-9). Odds ratios and 95% confidence intervals for associations between AF and AA were estimated using Cox regression and adjusted for comorbidities. Results: Our analyses included 116,225 AF cases and 116,225 propensity score-matched controls. Compared with the controls, the patients with AF exhibited a significantly increased risk of developing an AA (adjusted hazard ratio, HR 1.243, p < 0.001). Another cohort of 19,776 patients diagnosed with AA were identified, and 19,776 propensity score-matched patients were included as controls. Patients who had AA were also at an increased risk of developing AF (adjusted HR 1.187, p < 0.001). Heart failure (HF) was a common risk factor for both AA and AF. Conclusion: There are associations between AF and AA. HF is a mutual risk factor for the development of AF and AA.

Purpose: The present study compared the risk of ischemic stroke in atrial fibrillation (AF) patients receiving digoxin and amiodarone. Methods: A retrospective cohort study was conducted using the longitudinal population-based database of Taiwan’s National Health Insurance program. Patients with AF who received amiodarone or digoxin and were considered to have exposed to study drugs consecutively over 180 days during 2000–2010 were enrolled and divided into three groups: those who received amiodarone, digoxin, and amiodarone plus digoxin. All patients were followed from the index date to the occurrence of ischemic stroke, death, withdrawal from the insurance program, or December 31, 2011. Cox proportional hazard regression models were applied to determine the risk of ischemic stroke and associated risk factors. Results: The amiodarone, digoxin, and amiodarone plus digoxin cohorts comprised 797, 1419, and 376 patients, respectively. Overall, the patients who received digoxin (HR = 1.80; 95% CI = 1.41–2.31) or amiodarone plus digoxin (HR = 2.00; 95% CI = 1.49–2.68) had a higher risk of ischemic stroke, compared with those who received amiodarone. This risk was particularly at CHA2DS2VASc score of 2–5, but disappeared in those who received clopidogrel in the digoxin cohort. The risk of ischemic stroke in the amiodarone plus digoxin cohort did not differ significantly from that in the digoxin cohort (HR = 1.14; 95% CI = 0.90–1.44). Conclusion: Atrial fibrillation patients receiving digoxin are associated with a higher risk of ischemic stroke than are those receiving amiodarone. It is prudent to assess the stroke risk prior to applying treatment strategy for patients with AF. Strengths and Limitations of This Study - This study is a population-based design with a completeness and accuracy of data, national coverage in both study and control cohorts. All insurance claims were double-checked by medical specialists for peer review. - Information about serum levels of the drugs, coagulation status, and types of AF were unavailable in this administrative database.

This large population-based cohort study evaluated the association between certain critical illnesses and the incidence of newly diagnosed type 2 diabetes mellitus (T2DM) in Taiwan. Data were obtained from the Taiwan National Health Insurance Research Database. According to age, sex, and propensity score-matching, a cohort comprising 9528 patients with critical illness, including septicemia, septic shock, acute myocardial infarction (AMI), and stroke, and a control cohort of 9528 patients with no critical illness were identified. Cox proportional-hazard regression and competing-risk regression models were employed to evaluate the risk of developing T2DM. With the median follow-up periods (interquartile range) of 3.86 (1.64–6.93) and 5.12 (2.51–8.13) years for the patients in the critical illness and control cohorts, respectively, the risk of developing T2DM in the critical illness cohort was significantly higher than in the control cohort (adjusted hazard ratio, aHR = 1.32; 95 % confidence interval, CI 1.16–1.50). In the multivariate competing-risk regression models, the aHR of T2DM was 1.58 (95 % CI 1.45–1.72) in the critical illness cohort. Moreover, among the patients with these critical illnesses, those with septicemia or septic shock exhibited the highest risk of developing T2DM (aHR = 1.51, 95 % CI 1.37–1.67), followed by AMI compared with the control cohort. Our results suggest that patients with certain critical illnesses are associated with a high risk of developing T2DM. Clinicians should be aware of this association and intensively screen for T2DM in patients following diagnosis of critical illness.

Background To investigate the effect of carvedilol on the incidence of cancer in a large population-based cohort study. Methods Data were obtained from the Taiwan National Health Insurance Research Database. The cohort study included 6771 patients who received long-term carvedilol treatment between 2000 and 2010 (carvedilol cohort) and 6771 matched controls (noncarvedilol cohort). A Cox proportional hazards model was used to evaluate the risk of cancer in the patients treated with carvedilol. Results With the mean follow-up period of 5.17years and 4.93years in the carvedilol and noncarvedilol cohorts, respectively, the patients in the carvedilol cohort had a 26% reduction of cancer risk compared with those in the noncarvedilol cohort (hazard ratio [HR]=0.74; 95% confidence interval [CI]=0.63–0.87; p Conclusion This nationwide population-based cohort study demonstrated that long-term treatment with carvedilol is associated with reduced upper gastrointestinal tract and lung cancer risk, indicating that carvedilol could be a potential agent in these cancers prevention.

To investigate the relationship between chronic pancreatitis (CP) and inflammatory bowel disease (IBD) in a large population-based cohort study.Data was obtained from the Taiwan National Health Insurance Research Database. The cohort study comprised 17,796 patients newly diagnosed with CP between 2000 and 2010 and 71,164 matched controls. A Cox proportional hazards model was used for evaluating the risk of IBD in the CP and comparison cohorts.When examined with a mean follow-up period of 4.87 and 6.04 years for the CP and comparison cohorts, respectively, the overall incidence of IBD was 10.3 times higher in the CP cohort than in the comparison cohort (5.75 vs. 0.56 per 10,000 person-years). Compared with the comparison cohort, the CP cohort exhibited a higher risk of IBD, irrespective of age, sex, and presence or absence of comorbidities. Moreover, the CP cohort was associated with a significantly higher risk of Crohn's disease (adjusted hazard ratio [aHR] = 12.9, 95% confidence interval [CI] = 5.15-32.5) and ulcerative colitis (aHR = 2.80, 95% CI = 1.00-7.86).This nationwide population-based cohort study revealed a significantly higher risk of IBD in patients with CP compared with control group. Clinicians should notice this association to avoid delayed diagnosis of IBD in patients with CP.

Background: Thrombomodulin (TM) is a type of cell membrane-bound anticoagulant protein cofactor in the thrombin-mediated activation of protein C. Previous evidence has shown an association between TM polymorphisms and systemic inflammation. Conventional cardiopulmonary bypass (CPB), beating-heart CPB, and off-pump techniques have been widely used in cardiac surgery. However, these techniques may also cause systemic inflammatory responses in the patients. Whether TM polymorphisms are associated with systemic inflammation after cardiac surgery is still unclear. Methods: We analyzed the TM gene C1418T polymorphisms in 347 patients who underwent coronary artery bridge graft (CABG) surgery using allele-specific primers in a PCR assay. The clinical data during the hospital stay were collected and tested for correlations with the TM gene C1418T polymorphisms. Results: We separated the patients into two groups based on their TM C1418T genotype (CC genotype group and CT/TT genotype group). The days spent in an intensive care unit (ICU) and the incidence of fever in the ICU were significantly lower in the beating-heart CPB and off-pump groups than in the conventional CPB group. Additionally, the TM gene C1418T polymorphisms did not affect the early outcomes in patients in the beating-heart CPB and off-pump groups. Interestingly, in the conventional CPB group, patients with the CC genotype had a lower rate of fever, shorter duration of fever, and delay of ICU when compared with the CT/TT genotype. Conclusion: Surgeons may use a patient’s TM gene C1418T polymorphism to predict the strength of systemic inflammation and speculate on early outcomes during hospitalization before conventional CPB is performed.

miRNAs have emerged as important regulators of lipoprotein metabolism. Work over the past few years has demonstrated that miRNAs control the expression of most of the genes associated with high-density lipoprotein (HDL) metabolism, including the ATP transporters, ABCA1 and ABCG1, and the scavenger receptor SRB1. These findings strongly suggest that miRNAs regulate HDL biogenesis, cellular cholesterol efflux, and HDL cholesterol (HDL-C) uptake in the liver, thereby controlling all of the steps of reverse cholesterol transport. Recent work in animal models has demonstrated that manipulating miRNA levels including miR-33 can increase circulating HDL-C. Importantly, antagonizing miR-33 in vivo enhances the regression and reduces the progression of atherosclerosis. These findings support the idea of developing miRNA inhibitors for the treatment of dyslipidaemia and related cardiovascular disorders such as atherosclerosis. This review article focuses on how HDL metabolism is regulated by miRNAs and how antagonizing miRNA expression could be a potential therapy for treating cardiometabolic diseases.

To determine the incidence and risk of Parkinson disease (PD) in patients with Sjögren syndrome (SS) according to a nationwide population-based database. In total, 12,640 patients in the SS cohort and 50,560 in the non-SS cohort were enrolled from Taiwan's National Health Insurance Research Database from 2000 to 2010. We used the Cox multivariable proportional hazards model to determine the risk factors for PD in the SS cohort. We observed an increased incidence of PD in patients with SS, with a crude hazard ratio (HR) of 1.40 and an adjusted HR (aHR) of 1.23. The cumulative incidence of PD was 1.95% higher in the SS cohort than in the non-SS cohort. The SS cohort had an elevated HR under medication use, namely cevimeline and pilocarpine (crude HR, 1.28), hydroxychloroquine (crude HR, 1.43; aHR, 1.46), and methylprednisolone (crude HR, 2.21; aHR, 1.49). Patients receiving other non-hydroxychloroquine immunosuppressant therapies had a lower risk (aHR, 0.86) of PD. Furthermore, patients with SS aged 20 to 49 years had a 1.93-fold higher risk of PD than did those without SS (aHR, 1.93). The risk of PD was higher (aHR, 2.20) in patients with SS without comorbidities than in those with comorbidities. The aHR of PD significantly increased when the follow-up period exceeded 9 years (aHR, 1.93). We determined an increased risk of PD in patients with SS. Further investigation is warranted to determine the possible underlying mechanisms and the potential role of non-hydroxychloroquine immunosuppressants in ameliorating PD.

Rationale Esophageal chest pain is difficult to be identified, and the diagnosis requires a high index of clinical suspicion. Upon presentation, they are difficult to be differentiated from acute coronary syndrome (ACS) by symptomatology alone. Patient concerns We report a 71-year-old woman with multiple risk factors for coronary heart disease who presented with acute central spastic chest pain and was diagnosed as ACS in emergency department. Diagnoses Chest computed tomography revealed 1 radiopaque lesion over the upper-third of the esophagus. One fishbone with 3-pointed heads stuck in the esophagus was noted under esophagogastroscopic examination. Interventions The fishbone was extracted successfully via endoscopy under general anesthesia. Outcomes The woman was discharged uneventfully after 3 days' hospitalization. Lessons This case illustrates that, even in emergency, clinicians should always keep in mind the possibility of esophageal foreign body impaction when confronted with frank central chest pain without associated gastrointestinal symptoms. This holds true even in the scenario of multiple cardiovascular risk factors and absence of ingestion history.

Traumatic intracranial haemorrhage (ICH) leads to systemic inflammatory response and arrhythmia. Atrial fibrillation (AF), the most common arrhythmia, is associated with systemic inflammation. However, limited evidence is available regarding the association between traumatic ICH and AF.This study used the National Health Insurance Research Database, a nationwide population-based cohort, in Taiwan and total 130 171 individuals with traumatic ICH from 2000 to 2011 were identified. Furthermore, individuals without traumatic ICH were selected as a comparison cohort by the propensity score method. Individuals with prior history of AF were excluded from this study. The endpoint of interest was the occurrence of AF and the follow-up was terminated by the occurrence of AF, loss of follow-up or the passing of 31 December 2011.During the follow-up period, the incidence of AF was higher in patients with traumatic ICH than in those without traumatic ICH (4.24 vs 4.12 per 1000 person-years). After adjustment for age, sex and all AF-associated comorbidities, the individuals with traumatic ICH had a 1.25-fold increased risk of AF (HR=1.25, 95% CI=1.18 to 1.32; p0.001). Stratified by sex and age, the incidence of AF was consistently higher in the traumatic ICH group. Relative to the individuals without traumatic ICH and without comorbidities, the risk of AF was the highest in the individuals with both traumatic ICH and comorbidities; this risk was higher than that of the individuals with only traumatic ICH; it was also higher than the risk for those only with comorbidities.In this large-scale cohort study, the future risks of AF are higher in patients with traumatic ICH compared with the comparison cohort. Carefully monitoring the occurrence of AF and proper anticoagulation therapy might be important in patients with traumatic ICH.

Acute hyperglycemia is a frequent finding in patients presenting to the emergency department (ED) with acute myocardial infarction (AMI). The prognostic role of hyperglycemia in diabetic patients with AMI remains controversial. We retrospectively reviewed patients’ medical records to obtain demographic data, clinical presentation, major adverse cardiac events (MACEs), several clinical scores and laboratory data, including the plasma glucose level at initial presentation and HbA1c levels. The glycemic gap, which represents changes in serum glucose levels during the index event, was calculated from the glucose level upon ED admission minus the HbA1c-derived average glucose (ADAG). We enrolled 331 patients after the review of medical records. An elevated glycemic gap between admission serum glucose levels and ADAG were associated with an increased risk of mortality in patients. The glycemic gap showed superior discriminative power regarding the development of MACEs when compared with the admission glucose level. The calculation of the glycemic gap may increase the discriminative powers of established clinical scoring systems in diabetic patients presenting to the ED with AMI. In conclusion, the glycemic gap could be used as an adjunct parameter to assess the severity and prognosis of diabetic patients presenting with AMI. However, the usefulness of the glycemic gap should be further explored in prospective longitudinal studies.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder. Previous studies have suggested that chronic systemic inflammation increases the risk of Parkinson's disease (PD). This study examined the effects of IBD on the development of PD.In a nationwide population-based cohort of 23.22 million insured residents of Taiwan aged ≥ 20 years, we compared people diagnosed with IBD during 2000 to 2011 (n = 8373) with IBD-free individuals. Patients with PD were identified in the National Health Insurance Research Database. Using univariable and multivariable Cox proportion hazard regression models, we estimated the adjusted hazard ratio (aHR) for PD with a 95% confidence interval (CI) with adjustment for age, sex, and comorbidities.In the cohort, IBD was associated with an increased incidence of PD (crude hazard ratio = 1.43, 95% CI = 1.15-1.79). The risk was highest among individuals with Crohn's disease (aHR = 1.40, 95% CI = 1.11-1.77). In the multivariable model, the risk of PD was increased for men (aHR = 1.28, 95% CI = 1.05-1.56) and higher for patients with hypertension (aHR = 1.72, 95% CI = 1.33-2.24), coronary artery disease (aHR = 1.31, 95% CI = 1.04-1.66), or depression (aHR = 2.51, 95% CI = 1.82-3.46).We suggest that IBD is associated with an increased risk of PD. Patients with IBD should be aware of the potential risk for PD development.

Improved prevention and treatment of cardiovascular diseases is one of the challenges in Western societies, where ischemic heart disease and stroke are the leading cause of death. Early epidemiological studies have shown an inverse correlation between circulating high-density lipoprotein-cholesterol (HDL-C) and cardiovascular diseases. The cardioprotective effect of HDL is because of its ability to remove cholesterol from plaques in the artery wall to the liver for excretion by a process known as reverse cholesterol transport. Numerous studies have reported the role that micro-RNAs (miRNA) play in the regulation of the different steps in reverse cholesterol transport, including HDL biogenesis, cholesterol efflux, and cholesterol uptake in the liver and bile acid synthesis and secretion. Because of their ability to control different aspects of HDL metabolism and function, miRNAs have emerged as potential therapeutic targets to combat cardiovascular diseases. In this review, we summarize the recent advances in the miRNA–mediated control of HDL metabolism. We also discuss how HDL particles serve as carriers of miRNAs and the potential use of HDL-containing miRNAs as cardiovascular diseases biomarkers.

Supplemental Digital Content is available in the text, The aim of this large population-based cohort study was to determine whether pyogenic liver abscess (PLA) is associated with the risk of acute kidney injury (AKI). A total of 31,815 patients aged 20 years or older diagnosed with PLA for the first time during hospitalization between 2000 and 2011 were included in a PLA cohort, and 127,620 age- and sex-matched patients without PLA were included in a non-PLA cohort. The incidence and the risk of the first attack of AKI at the end of 2011 were measured. Cox proportional hazard regression models were used to analyze the risk of AKI. In mean follow-up periods of 4.36 and 4.94 years for the PLA and non-PLA cohorts, respectively, the overall incidence of AKI was 1.51-fold greater in the PLA cohort than in the non-PLA cohort (9.25 vs 6.11 events per 1000 person-years; 95% confidence intervals [CIs] = 1.42–1.61). After we controlled for potential confounding factors, the adjusted hazard ratio (aHR) of AKI was 1.36 (95% CIs = 1.27–1.46) for the PLA cohort compared with the non-PLA cohort. Moreover, among patients without comorbidities, the risk of AKI remained higher in the PLA cohort compared with the non-PLA cohort (aHR: 1.91, 95% CIs = 1.59–2.29). This study suggests that PLA associates with an increased risk of AKI. Clinicians should be aware of the potential risk of AKI after diagnosis of PLA.

Despite popular use of piperacillin, the dire neurotoxicity associated with piperacillin still goes unrecognized, leading to a delay in appropriate management. We report a 57-year-old woman with end-stage renal disease receiving continuous ambulatory peritoneal dialysis (CAPD), who developed slurred speech, tremor, bizarre behavior, progressive mental confusion, and 2 episodes of generalized tonic-clonic seizure (GTCS) after 5 doses of piperacillin/tazobactam (2 g/250 mg) were given for bronchiectasis with secondary infection. The laboratory data revealed normal plasma electrolyte and ammonia levels but leukocytosis. Neurologic examinations showed dysarthria and bilateral Babinski sign. Computed tomography of brain and electroencephalogram were unremarkable. Despite the use of antiepileptic agents, another GTCS episode recurred after the sixth dose of piperacillin/tazobactam. Brain magnetic resonance imaging did not demonstrate acute infarction and organic brain lesions. Initiation of high-flux hemodialysis rapidly reversed the neurologic symptoms within 4 hours. Piperacillin-induced encephalopathy should be considered in any uremic patients with unexplained neurological manifestations. CAPD is inefficient in removing piperacillin, whereas hemodialysis can rapidly terminate the piperacillin-induced encephalopathy.

Traumatic intracranial hemorrhage (ICH) is prevalent worldwide with long-term consequences, including disabilities. However, studies on the association of traumatic ICH with coronary artery disease (CAD) are scant. Therefore, this study explored the aforementioned association in a large-scale, population-based cohort. A total of 128,997 patients with newly diagnosed traumatic ICH and 257,994 age- and sex-matched patients without traumatic ICH from 2000 to 2010 were identified from Taiwan's National Health Insurance Research Database. The Kaplan–Meier method was used for measuring the cumulative incidence of CAD in each cohort. Cox proportional regression models were used for evaluating the risk of CAD in patients with and without traumatic ICH and for comparing the risk between the 2 cohorts. The Kaplan–Meier analysis revealed that the cumulative incidence curves of CAD were significantly higher in patients with traumatic ICH than in those without ICH (log-rank test, P

Acute myocardial infarction (AMI) is uncommon in the acute phase of acute ischemic stroke (AIS) and occurs in approximately 1% of the population. Here, we report a paradoxical case of AMI during tissue plasminogen activator (t-PA) infusion for AIS. We review and analyze the previously reported cases. We found that only patients with AMI which occurred after thrombolytic therapy for AIS who received an adequate combination of anticoagulation plus percutaneous coronary intervention survived their events. Several mechanisms have been proposed for the development of AMI after thrombolytic therapy. These mechanisms include fragmented intra-cardiac thrombus, intensified platelet aggregation that may lead to an increased potential for intra-cardiac thrombus formation, and a reduction in clot-associated plasminogen that may lead to a paradoxical hypercoagulable state of the coronary arteries. Currently, there is no consensus regarding this specific scenario. We propose that the therapeutic benefit and the potential risk of hemorrhagic complications should be further investigated and individualized. In patients who receive thrombolytic therapy for AIS and who then develop post-thrombolytic AMI, we suggest that the maximum treatment for the subsequent AMI be instituted promptly to avoid short-term mortality.

The effect of glycemic control on the prognosis of nondiabetic patients after acute myocardial infarction (AMI) remains uncertain. We investigated whether glycated hemoglobin (HbA1c) is associated with adverse outcomes after AMI in nondiabetic patients. In this observational study, we enrolled nondiabetic patients with AMI in the emergency department of 2 medical centers from January 2011 to September 2014. All patients received primary percutaneous coronary intervention and were divided into 4 groups according to the interquartile range of average HbA1c level (Group I, ≤5.6%; Group II, 5.6%-5.8%; Group III, 5.8%-6.0%; and Group IV, >6.0%). Multivariate logistic analysis was performed to estimate the correlation of HbA1c with major adverse cardiac events (MACEs) after AMI. In total, 267 eligible patients were enrolled; 48 patients (18%) developed MACEs within a median follow-up of 178 days. Univariate analysis showed HbA1c > 6.0%, with a higher risk of MACEs in Group IV than in Group I (odds ratio [OR]: 2.733; 95% confidence interval [CI]: 1.123-6.651 vs OR: 1.511; 95% CI: 0.595-3.835). Multivariate analysis revealed an approximately 3.8 times higher risk of MACEs in Group IV than in Group I (OR: 3.769; 95% CI: 1.30-10.86). The HbA1 level is a significant predictor of MACEs after AMI in nondiabetic patients.

An 86-year-old man presented with sudden onset of dyspnea during hospitalization. Initial electrocardiography (ECG) showed poor R-wave progression of precordial leads with elevation of troponin I. Tension pneumothorax was subsequently diagnosed and the ECG returned to normal after resolution of clinical compromise.

Although ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a well-known paraneoplastic phenomenon, an association with large-cell neuroendocrine carcinoma of the lung (LCNEC) has not been reported. We describe a 63-year-old man with metastatic LCNEC to the left temporomandibular joint (TMJ) who presented with progressive muscle weakness and bilateral lower leg edema for 2 weeks. He did not have a typical Cushingoid appearance nor used diuretics. His newly noted hypertension, hypokalemia (plasma potassium (K + ) concentration 1.8mEq/L) with renal K + wasting, and metabolic alkalosis suggested a state of mineralocorticoid excess. His plasma renin activity and aldosterone concentrations were low, but cortisol and ACTH levels were extremely elevated, consistent with ACTH-dependent Cushing's syndrome. Nonsuppressible plasma cortisol level and normal sella turcica on magnetic resonance imaging pointed to EAS. A strongly positive stain for ACTH from the metastatic left TMJ mass supported LCNEC-related EAS. His hypokalemia and hypertension were controlled with spironolactone and K + supplementation. This is the first reported case of EAS in LCNEC and should be kept in mind as a cause of hypokalemia in lung cancer patients.

Migration of vascular smooth muscle cells (VSMCs) into the intima is considered to be a vital event in the pathophysiology of atherosclerosis. Despite substantial evidence supporting the pathogenic role of Toll-like receptor 4 (TLR4) in the progression of atherogenesis, its function in the regulation of VSMC migration remains unclear. The goal of the present study was to elucidate the mechanism by which TLR4 regulates VSMC migration. Inhibitor experiments revealed that TLR4-induced IL-6 secretion and VSMC migration were mediated via the concerted actions of MyD88 and TRIF on the activation of p38 MAPK and ERK1/2 signaling. Neutralizing anti-IL-6 antibodies abrogated TLR4-driven VSMC migration and F-actin polymerization. Blockade of p38 MAPK or ERK1/2 signaling cascade inhibited TLR4 agonist-mediated activation of cAMP response element binding protein (CREB). Moreover, siRNA-mediated suppression of CREB production repressed TLR4-induced IL-6 production and VSMC migration. Rac-1 inhibitor suppressed TLR4-driven VSMC migration but not IL-6 production. Importantly, the serum level of IL-6 and TLR4 endogenous ligand HMGB1 was significantly higher in patients with coronary artery diseases (CAD) than in healthy subjects. Serum HMGB1 level was positively correlated with serum IL-6 level in CAD patients. The expression of both HMGB1 and IL-6 was clearly detected in the atherosclerotic tissue of the CAD patients. Additionally, there was a positive association between p-CREB and HMGB1 in mouse atherosclerotic tissue. Based on our findings, we concluded that, upon ligand binding, TLR4 activates p38 MAPK and ERK1/2 signaling through MyD88 and TRIF in VSMCs. These signaling pathways subsequently coordinate an additive augmentation of CREB-driven IL-6 production, which in turn triggers Rac-1-mediated actin cytoskeleton to promote VSMC migration.

Diabetes mellitus (DM) is a metabolic disease that is increasing worldwide. Furthermore, it is associated with the deregulation of vascular-related functions, which can develop into major complications among DM patients. Endothelial colony forming cells (ECFCs) have the potential to bring about medical repairs because of their post-natal angiogenic activities; however, such activities are impaired by high glucose- (HG) and the DM-associated conditions. Far-infrared radiation (FIR) transfers energy as heat that is perceived by the thermoreceptors in human skin. Several studies have revealed that FIR improves vascular endothelial functioning and boost angiogenesis. FIR has been used as anti-inflammatory therapy and as a clinical treatment for peripheral circulation improvement. In addition to vascular repair, there is increasing evidence to show that FIR can be applied to a variety of diseases, including cardiovascular disorders, hypertension and arthritis. Yet mechanism of action of FIR and the biomarkers that indicate FIR effects remain unclear. MicroRNA-134 (miR-134-5p) was identified by small RNA sequencing as being increased in high glucose (HG) treated dfECFCs (HG-dfECFCs). Highly expressed miR-134 was also validated in dmECFCs by RT-qPCR and it is associated with impaired angiogenic activities of ECFCs. The functioning of ECFCs is improved by FIR treatment and this occurs via a reduction in the level of miR-134 and an increase in the NRIP1 transcript, a direct target of miR-134. Using a mouse ischemic hindlimb model, the recovery of impaired blood flow in the presence of HG-dfECFCs was improved by FIR pretreatment and this enhanced functionality was decreased when there was miR-134 overexpression in the FIR pretreated HG-dfECFCs. In conclusion, our results reveal that the deregulation of miR-134 is involved in angiogenic defects found in DM patients. FIR treatment improves the angiogenic activity of HG-dfECFCs and dmECFCs and FIR has potential as a treatment for DM. Detection of miR-134 expression in FIR-treated ECFCs should help us to explore further the effectiveness of FIR therapy.

A 22-year-old Chinese man presented with sudden onset of generalised muscular weakness and paralysis upon awakening in the morning, due to sporadic periodic paralysis (SPP), a type of hypokalaemic periodic paralysis (HPP) without hyperthyroidism or familial history of paralysis. Laboratory studies showed marked hypokalaemia (K(+) 1.6 mmol/litre). He received intravenous KCl supplementation at a rate of 0.14 mmol/kg/h and developed a paradoxical fall in serum K(+) concentration from 1.6 to 1.4 mmol/litre during KCl therapy. After 160 mmol KCl supplementation his muscular strength recovered, but muscular paralysis recurred 2 h later. Acute recurrent hypokalaemia was the presumptive initial diagnosis and intravenous KCl supplementation was briefly reinitiated. Despite no obvious abnormalities on ECG monitoring, a 12-lead ECG clearly demonstrated tented T waves in the precordial leads suggestive of hyperkalaemia, later found to be 6.9 mmol/litre. After treatment with intravenous calcium gluconate, insulin and loop diuretics, his serum K(+) concentration fell to 4.7 mmol/litre and muscular paralysis resolved in 3 h.