HNMT Upregulation Induces Cancer Stem Cell Formation and Confers Protection against Oxidative Stress through Interaction with HER2 in Non-Small-Cell Lung Cancer.

BACKGROUND: The treatment of non-small-cell lung cancer (NSCLC) involves platinum-based chemotherapy. It is typically accompanied by chemoresistance resulting from antioxidant properties conferred by cancer stem cells (CSCs). Human epidermal growth factor receptor 2 (HER2) enhances CSCs and antioxidant properties in cancers, including NSCLC. METHODS: Here, we elucidated the role of histamine N-methyltransferase (HNMT), a histamine metabolism enzyme significantly upregulated in NSCLC and coexpressed with HER2. HNMT expression in lung cancer tissues was determined using quantitative reverse transcription PCR (RT-qPCR). A publicly available dataset was used to determine HNMT's potential as an NSCLC target molecule. Immunohistochemistry and coimmunoprecipitation were used to determine HNMT-HER2 correlations and interactions, respectively. HNMT shRNA and overexpression plasmids were used to explore HNMT functions in vitro and in vivo. We also examined miRNAs that may target HNMT and investigated HNMT/HER2's role on NSCLC cells' antioxidant properties. Finally, how HNMT loss affects NSCLC cells' sensitivity to cisplatin was investigated. RESULTS: HNMT was significantly upregulated in human NSCLC tissues, conferred a worse prognosis, and was coexpressed with HER2. HNMT depletion and overexpression respectively decreased and increased cell proliferation, colony formation, tumorsphere formation, and CSCs marker expression. Coimmunoprecipitation analysis indicated that HNMT directly interacts with HER2. TARGETSCAN analysis revealed that HNMT is a miR-223 and miR-3065-5p target. TBHp treatment increased HER2 expression, whereas shHNMT disrupted the Nuclear factor erythroid 2-related factor 2 (Nrf2)/ hemeoxygenase-1 (HO-1)/HER2 axis and increased reactive oxygen species accumulation in NSCLC cells. Finally, shHNMT sensitized H441 cells to cisplatin treatment in vitro and in vivo. CONCLUSIONS: Therefore, HNMT upregulation in NSCLC cells may upregulate HER2 expression, increasing tumorigenicity and chemoresistance through CSCs maintenance and antioxidant properties. This newly discovered regulatory axis may aid in retarding NSCLC progression and chemoresistance.

A systematic review and meta-analysis of the comparison of performance among step-tip, split-tip, and symmetrical-tip hemodialysis catheters.

OBJECTIVE: Patients with end-stage renal disease need vascular access to ensure sufficient blood flow during hemodialysis (HD). Patients who are poor candidates for arteriovenous access creation require long-term catheter placement. Problems such as dialysate recirculation, thrombosis, catheter-related infections, and malfunction can occur with HD catheters. Different tip designs (step, split, and symmetrical) have been developed to ameliorate the catheter-related problems. The aim of the study was to compare the efficacy and safety of split-tip, step-tip, and symmetrical-tip HD catheters. METHODS: The PubMed, Embase, Cochrane Library, and Scopus databases and the ClinicalTrials.gov registry were searched for studies published before November 2017. Studies comparing the clinical and rheologic outcomes of step-, split-, or symmetrical-tip catheters in patients undergoing HD were included in this meta-analysis. We conducted meta-analyses using random-effects models. The primary outcomes were catheter survival time and incidence of functioning catheters. The secondary outcomes were delivered blood flow rate, blood recirculation rate, and incidence of catheter-related complications. RESULTS: Seven randomized controlled trials and one retrospective study with a total of 988 patients were included. No significant differences were observed in the delivered blood flow rate (weighted mean difference, -5.37 mL/min; 95% confidence interval [CI], -23.75 to 13.02), incidence of catheter-related infections (risk ratio [RR], 1.18; 95% CI, 0.63-2.22), or incidence of catheter-related thrombosis (RR, 1.29; 95% CI, 0.64-2.59) between step-tip catheters and advanced (both split-tip and symmetrical-tip) catheters. Moreover, a meta-analysis of the incidence of functioning catheters at 1 month, 6 months, and 12 months revealed that the outcome of step-tip catheter use was better than that of split-tip catheter use, but with a significant difference only at 6 months (RR, 1.22; 95% CI, 1.02-1.46). CONCLUSIONS: None of the catheter types exhibited unique features that can enhance their suitability for application. Hence, catheters can be selected by also considering different factors, including costs, ease of procedures, expertise of the clinician, and education and preference of the patient.

Fasting but not changes of plasma metabolome during oral glucose tolerance tests improves the diagnosis of severe coronary arterial stenosis.

BACKGROUND: Noninvasive stress tests for the diagnosis of significant coronary arterial stenosis requiring intervention are not perfect. We investigated whether plasma metabolome during the oral glucose tolerance test (OGTT) can improve the diagnosis. METHODS: A total of 117 subjects with positive stress test results who received coronary angiography were recruited. After excluding subjects with a history of myocardial infarction and subjects who did not receive OGTT, the 18 subjects without significant stenosis were selected as controls. Another 18 age- and sex-matched subjects with significant stenosis were selected as cases. Plasma metabolome from samples obtained in fasting, 30 and 120 min after OGTT was measured using liquid chromatography combined with time-of-flight mass spectrometry. RESULTS: We found five metabolites which can identify patients with significant stenosis independent to clinical risk factors, including diabetes, hypertension, hypercholesterolaemia, smoking and history of percutaneous coronary intervention (all P < 0·05). The area under the receiver operating characteristic (AUROC) curve of these metabolites was 0·799-0·818 at fasting and 30 min after OGTT. The addition of metabolites to clinical factors increases the AUROC (0·616, 95%CI 0·429-0·803 for model with clinical factors only; 0·824, 95%CI 0·689-0·959 for model with four metabolites and clinical factors). The changes of plasma metabolite levels during OGTT did not significantly improve the diagnostic performance. CONCLUSIONS: Fasting plasma metabolome, but not change of plasma metabolome during OGTT, can improve the diagnosis of significant stenosis in patients with positive noninvasive stress test results.

Prostaglandin E2 potentiates mesenchymal stem cell-induced IL-10+IFN-γ+CD4+ regulatory T cells to control transplant arteriosclerosis.

Mesenchymal stem cells (MSCs) are known for their immunomodulatory functions. We previously demonstrated that bone marrow-derived MSCs effectively control transplant arteriosclerosis (TA) by enhancing IL-10(+) and IFN-γ(+) cells. The objective of this study is to elucidate the mechanism by which MSCs induce IL-10(+)IFN-γ(+)CD4(+) regulatory T type 1 (T(R)1)-like cells. In an MLR system using porcine PBMCs, MSC-induced IL-10(+)IFN-γ(+)CD4(+) cells, which confer resistance to allogeneic proliferation in an IL-10-dependent manner, resemble T(R)1-like cells. Both cyclooxygenase-derived PGE(2) and IDO help to induce T(R)1-like cells by MSCs. MSCs constitutively secrete PGE(2), which is augmented in allogeneic reactions. However, T(R)1-like cells were deficient in PGE(2) and 4-fold less potent than were MSCs in suppressing MLR. PGE(2) mimetic supplements can enhance the immunosuppressive potency of T(R)1-like cells. In a porcine model of allogeneic femoral arterial transplantation, MSC-induced T(R)1-like cells combined with PGE(2), but not either alone, significantly reduced TA at the end of 6 wk (percentage of luminal area stenosis: T(R)1-like cells + PGE(2): 11 ± 10%; PGE(2) alone: 93 ± 8.7%; T(R)1-like cells alone: 88 ± 2.4% versus untreated 94 ± 0.9%, p < 0.001). These findings indicate that PGE(2) helps MSC-induced IL-10(+)IFN-γ(+)CD4(+) T(R)1-like cells inhibit TA. PGE(2) combined with MSC-induced T(R)1-like cells represents a new approach for achieving immune tolerance.

Mechanisms of early and delayed stroke after systematic off-pump coronary artery bypass.

BACKGROUND/PURPOSE: Stroke is one of the most devastating complications after cardiac surgery. Off-pump coronary artery bypass (OPCAB) has been reported to offer a lower risk of stroke. However, limited information was available on timing and mechanisms of stroke after OPCAB. We sought to assess the incidence, timing, and mechanisms of stroke after OPCAB. METHODS: A retrospective review of 1010 patients undergoing systematic OPCAB between 2001 and 2012. Stroke was defined as any focal or global neurologic deficits lasting for more than 24 hours. Stroke was classified as early stroke when it occurred less than 24 hours postoperatively, and delayed stroke when it occurred more than 24 hours postoperatively. Stroke mechanisms were classified as embolic or hypoperfusion. RESULTS: In a total of 10 patients (1.0%) 11 episodes of stroke developed after OPCAB. Early stroke occurred in five (0.5%) patients and delayed stroke occurred in six (0.6%) patients. Of five early strokes, the mechanisms were embolic in two (40%) and hypoperfusion in three (60%). Of six delayed strokes, the mechanisms were embolic in five (83%) and unknown in one. Of six delayed strokes, all the patients had diabetes mellitus and acute cardiac events prior to surgery, and five patients had postoperative atrial fibrillation. CONCLUSION: The incidence of stroke after systematic OPCAB was low. Early and delayed strokes were equally distributed. Stroke mechanisms were predominantly embolic. Early and delayed stroke differed in their mechanisms. Early and delayed stroke should be considered as two separate entities and different preventive strategies should be applied in future intervention.

Malignant ventricular arrhythmias after off-pump coronary artery bypass.

BACKGROUND/PURPOSE: Sustained ventricular tachycardia and ventricular fibrillation (VT/VF) are rare complications after coronary surgery. Off-pump coronary artery bypass (OPCAB) was developed to decrease postoperative complications. No studies to date have specifically addressed VT/VF after OPCAB. We sought to assess the incidence, risk factors, and outcome of VT/VF after OPCAB. METHODS: The study included a retrospective review of 1010 patients undergoing OPCAB between 2000 and 2012. Data were compared between the VT/VF patients and control patients who were the first cases of OPCAB in each month during the study period and did not have VT/VF. RESULTS: Twenty-three patients (2.3%) developed VT/VF after OPCAB. The hospital mortality rate was 17.4%. In univariate analysis, the risk factors for VT/VF were old age, rapid heart rate, prolonged corrected QT interval, severe congestive heart failure, poor left ventricular ejection fraction, large left ventricular end-diastolic diameter, chronic kidney disease, preoperative dialysis, low blood hemoglobin level, preoperative intubation, recent myocardial infarction, high European System for Cardiac Operative Risk Evaluation, urgent/emergent operation, use of intra-aortic balloon pump, conversion to on-pump beating heart, postoperative dialysis, and no use of beta-blockers after operation. Multivariate analysis identified preoperative corrected QT interval > 426 milliseconds [odds ratio (OR) = 4.501; 95% confidence interval (CI) = 1.153-17.570] and estimated glomerular filtration rate < 30 mL/minute/1.73 m(2) (OR = 4.876; 95% CI = 1.112-21.374) as independent risk factors. CONCLUSION: Postoperative VT/VF was rare after OPCAB but was associated with high mortality. Prolonged corrected QT interval and chronic kidney disease were independent risk factors. Recognition of these risk factors, proper prevention, and early intervention may improve survival.

Incidence, risk factor, and prognosis of end-stage renal disease after heart transplantation in Chinese recipients.

BACKGROUND/PURPOSE: End-stage renal disease (ESRD) is an important complication arising after heart transplantation. At least 3-10% of recipients reach ESRD within 10 years after transplant. The incidence of ESRD in Chinese recipients has not been reported. Here we sought to assess the incidence, prognosis, and risk factors for ESRD in Chinese recipients. METHODS: We conducted a retrospective analysis of 248 heart recipients who survived >1 year from 1998 through 2007. ESRD was defined as the requirement of maintenance dialysis. RESULTS: Renal dysfunction was present in 20 patients (8%) prior to transplant. With a follow-up duration of 5.8 ± 3.9 years, 30 patients developed ESRD. The cumulative incidence of ESRD after heart transplantation was 2.1% ± 0.9%, 6.5% ± 1.8%, 16.8% ± 3.3%, and 36.5% ± 9.5% at 2, 5, 10, and 15 years after transplant, respectively. Median onset of ESRD was 6.9 years after transplant. Actuarial survival after dialysis was 74.8% ± 8.3%, 66.6% ± 9.2%, and 43.6% ± 12.6% at 1, 2, and 5 years, respectively. Independent risk factors for ESRD included pretransplant serum creatinine (hazard ratio, 1.84; p = 0.001), presence of diabetes prior to transplant (hazard ratio, 2.51; p = 0.017), and old age at transplant (hazard ratio, 1.05; p = 0.008). CONCLUSION: There was a high incidence of ESRD in Chinese heart recipients. Patients with ESRD had poor prognosis after dialysis.

Primary Infected Aortic Aneurysm: Clinical Presentation, Pathogen, and Outcome.

PURPOSE: Infected aneurysm of the aorta and adjacent arteries is rarely occurring and can be fatal without surgical intervention. Within the medical community, the most efficacious treatment strategy to address infected aortic aneurysm remains controversial. In this study, we have reviewed our treatment experience with 109 patients. METHODS: We included in our study all consecutive patients treated for primary infected aortic aneurysm at our facility between 1995 and 2011. Aneurysm-related mortality was defined as the presence of in-hospital and late mortality related to infection or postoperative complications. RESULTS: The median patient age was 72 years (range, 35-88), and 87 (80%) were male. Pathogen was isolated in 101 patients, and the most common microorganism identified was non-typhoid Salmonella in 61 (60%), followed by Staphylococcus aureus in 16 (16%) and Streptococci species in 7 (7%). Eighty-five (78%) patients underwent surgical treatment. Surgery included open repair with in-situ graft replacement in 77 (71%) and endovascular repair in 8 (7%). The aneurysm-related mortality rate was 67% in medically treated and 21% in surgically treated patients, with a median follow-up duration of 31.5 months (range 1-189). Additionally, risk factors for aneurysm-related mortality included old age, chronic lung disease, psoas muscle abscess, short duration of preoperative antibiotics, no operation, and probably endovascular repair. CONCLUSIONS: Non-typhoid Salmonella was the most common pathogen found in our study group patients with infected aortic aneurysm. It appears that prolonged preoperative antibiotic treatment followed by open in-situ graft replacement remains the preferred and most effective treatment strategy. KEY WORDS: Infected aortic aneurysm; Outcome; Pathogen; Surgery.

Role of Left Main Coronary Artery Stenosis on Intraoperative Conversion and Mortality in Off-Pump Coronary Artery Bypass.

BACKGROUND: Intraoperative conversion is a major threat in off-pump coronary artery bypass (OPCAB). The conversion rate depends on patient selection and surgeon experience. Previous studies have demonstrated the feasibility of OPCAB for patients with left main coronary artery stenosis (LMCAS) ≥ 50%. However, no studies have focused on the role of LMCAS ≥ 90%. We sought to assess the impact of LMCAS ≥ 90% on the conversion rate and mortality in OPCAB. METHODS: We conducted a retrospective review of 1055 consecutive unselected patients undergoing OPCAB between 2000 and 2012. The patients in our study were divided into 3 groups by the severity of LMCAS. RESULTS: LMCAS was < 50% in 704, 50-90% in 266, and ≥ 90% in 85 patients. LMCAS was not associated with major postoperative complications and hospital mortality, although preoperative cardiogenic shock was present in 6.3%. Overall, the conversion rate was 10.1%:11.4% in LMCAS < 50%, 5.6% in LMCAS 50-90%, and 14.1% in LMCAS ≥ 90%. Operation status, cardiogenic shock, left ventricular ejection fraction < 30% and operation before 2007 were noted as independent predictors of conversion. The overall hospital mortality rate was 5.1%: 4.8% in LMCAS < 50%, 4.5% in LMCAS 50-90%, and 9.4% in LMCAS ≥ 90%. Operation status, cardiogenic shock, left ventricular ejection fraction < 30% and intraoperative conversion were observed to be independent predictors of mortality. However, LMCAS did not predict either conversion or hospital mortality. CONCLUSIONS: LMCAS ≥ 90% was not an independent predictor of intraoperative conversion or hospital mortality in OPCAB. KEY WORDS: Conversion; Left main coronary artery stenosis; Off-pump coronary artery bypass.

Effect of Annual Influenza Vaccination on the Risk of Lung Cancer Among Patients With Hypertension: A Population-Based Cohort Study in Taiwan.

Objectives: Lung cancer is a main contributor to all newly diagnosed cancers worldwide. The chemoprotective effect of the influenza vaccine among patients with hypertension remains unclear. Methods: A total of 37,022 patients with hypertension were retrospectively enrolled from the Taiwan National Health Insurance Research Database. These patients were further divided into a vaccinated group (n = 15,697) and an unvaccinated group (n = 21,325). Results: After adjusting for sex, age, comorbidities, medications, level of urbanization and monthly income, vaccinated patients had a significantly lower risk of lung cancer occurrence than unvaccinated patients (adjusted hazard ratio [aHR]: 0.56, 95% confidence interval [CI]: 0.47-0.67). A potential protective effect was observed for both sexes and in the elderly age group. With a greater total number of vaccinations, a potentially greater protective effect was observed (aHR: 0.75, 95% CI 0.60-0.95; aHR: 0.66, 95% CI: 0.53-0.82; aHR: 0.26, 95% CI: 0.19-0.36, after receiving 1, 2-3 and ≥4 vaccinations, respectively). Conclusion: Influenza vaccination was associated with a lower risk of lung cancer among patients with hypertension. The potentially chemoprotective effect appeared to be dose dependent.

Stress-induced cardiomyopathy caused by heat stroke.

Heat stroke is defined by central nervous system abnormalities and failure of proper maintenance of thermoregulation as a result of high core body temperature ensuing from exposure to high environmental temperatures or strenuous exercise. Common complications include acute respiratory distress syndrome, disseminated intravascular coagulation, acute renal injury, hepatic injury, and rhabdomyolysis. Myocardial injury may also occur during heat stroke, resulting in cardiac enzyme increase and ST-segment changes on the ECG. Such findings might behave as diagnostic pitfalls by mimicking the presentation of coronary artery occlusive myocardial infarction. A previous case report described a patient with heat stroke and ST-segment elevation, in which the definite cause of the ST-segment elevation was unclear; however, acute myocardial infarction caused by coronary artery disease was ruled out according to the clinical signs, serial ECG changes, and serum level of cardiac biomarkers. Stress-induced cardiomyopathy (Takotsubo cardiomyopathy) was suspected, but it could not be confirmed because of the lack of coronary angiography. We herein report a case of heat stroke presenting with ST-segment elevation and cardiogenic shock. Coronary angiography was performed and coronary artery occlusive myocardial infarction was ruled out because of the presence of patent coronary arteries. Left ventriculography showed midventricular and apical hypokinesis, and stress-induced cardiomyopathy was then determined to be the appropriate diagnosis. Heat stroke causes increase of serum catecholamine levels, in which oversecretion and abnormal responses to catecholamines are a possible cause of stress-induced cardiomyopathy. Catecholamines may therefore be the key in linking heat stroke and stress-induced cardiomyopathy.

Tanshinone IIA attenuates cyclic strain-induced endothelin-1 expression in human umbilical vein endothelial cells.

1. Tanshinone IIA, one of the active components of the Radix of Salvia miltiorrhiza, is used in traditional Chinese medicine to treat cardiovascular diseases. However, the intracellular mechanism of action of tanshinone IIA remain to be determined. The aims of the present study were to test the hypothesis that tanshinone IIA alters strain-induced endothelin (ET)-1 expression and nitric oxide (NO) production, as well as to identify the putative signalling pathways involved, in human umbilical vein endothelial cells (HUVEC). 2. Cultured HUVEC were exposed to cyclic strain in the presence of 1-10 µmol/L tanshinone IIA. Expression of ET-1 was examined by reverse transcription-polymerase chain reaction and ELISA. Phosphorylation of endothelial NO synthase (eNOS) and activating transcription factor (ATF) 3 was assessed by western blot analysis. 3. Tanshinone IIA (3 and 10 µmol/L) inhibited strain-induced ET-1 expression. In contrast, NO production, eNOS phosphorylation and ATF3 expression were enhanced by tanshinone IIA. The eNOS inhibitor N(G) -nitro-L-arginine methyl ester (l-NAME; 100 µmol/L), the phosphatidylinositol 3-kinase inhibitor LY294002 (5 µmol/L) and the soluble guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ; 10 µmol/L) inhibited tanshinone IIA-induced increases in ATF3 expression. Moreover, treatment of HUVEC with either an NO donor (3,3-bis [aminoethyl]-1-hydroxy-2-oxo-1-triazene; 500 µmol/L) or an ATF3 activator (carbobenzoxy-L-leucyl-L-leucyl-L-leucinal; 5 µmol/L) resulted in the repression of strain-induced ET-1 expression. The inhibitory effect of tanshinone IIA on strain-induced ET-1 expression was significantly attenuated by l-NAME, ODQ and the transfection of small interfering RNA for ATF3. 4. In conclusion, tanshinone IIA inhibits strain-induced ET-1 expression by increasing NO and upregulating ATF3 in HUVEC. The present study provides important new insights into the molecular pathways that may contribute to the beneficial effects of tanshinone IIA in the cardiovascular system.

Influenza Vaccination and Risk of Stroke in Women With Chronic Obstructive Pulmonary Disease: A Nationwide, Population-Based, Propensity-Matched Cohort Study.

Backgrounds: The risk of stroke is higher among patients with chronic obstructive pulmonary disease (COPD) than among the healthy population. Moreover, women generally have worse long-term stroke outcomes than men. Methods: The data of 6681 women with COPD (aged ≥ 65 years) registered in Taiwan's National Health Insurance Research Database were retrospectively analyzed from January 1, 2001 to December 31, 2011. After 1:1 propensity score matching, the patients were divided into vaccinated and unvaccinated groups. Results: In total, 5102 women were enrolled. The vaccinated group had a significantly lower risk of total, hemorrhagic, and ischemic stroke than the unvaccinated group (adjusted hazard ratio [aHR]: 0.60, 95% confidence interval [CI]: 0.54-0.67; aHR: 0.59, 95% CI: 0.43-0.83; and aHR: 0.59, 95% CI: 0.52-0.68, respectively). A lower risk of stroke was observed among the women aged 65-74 and ≥75 years, and the association was dose-dependent in all types of stroke (aHR: 1.08, 95% CI: 0.92-1.26; aHR: 0.70, 95% CI: 0.60-0.82; and aHR: 0.32, 95% CI: 0.26-0.38 for those vaccinated 1, 2 to 3, and ≥4 times, respectively, during the follow-up period). Women with a CHA2DS2-VASc score (conditions and characteristics included congestive heart failure, hypertension, diabetes, stroke, vascular disease, age, and sex) of 2-3 and ≥4 had a significantly lower risk of ischemic stroke while receiving more vaccinations. A smaller significant lower risk of hemorrhagic stroke after more than 4 times of vaccination was noted in the women with a CHA2DS2-VASc score of ≥4. Both interrupted and non-interrupted vaccination was associated with lower risk of stroke occurrence. Conclusion: Influenza vaccination is associated with a lower risk of total, hemorrhagic, and ischemic stroke among women with COPD, and the association is dose-dependent. However, the findings may be limited by unmeasurable confounders. Further investigations on this subject are warranted.

Association between sleep disorder and atrial fibrillation: A nationwide population-based cohort study.

OBJECTIVES: Sleep disorder (SD), especially sleep apnea, and its effect on atrial fibrillation (AF) are gathering attention. However, other SDs may also play an essential role in AF. The aim of the study is to investigate the effects of other SDs on the risk of atrial fibrillation development. METHODS: This study investigated the risk of AF in people diagnosed with SD compared with that in age and sex-matched unaffected individuals. This longitudinal, nationwide, population-based cohort study was conducted using data from the Taiwan National Health Insurance Research Database (NHIRD) of individuals diagnosed with SD from January 1, 2001, to December 31, 2012. RESULTS: The sample consisted of 193,288 people with the SD, which include of 4406 people with sleep apnea, 73,704 people with insomnia, 107,395 people with sleep disturbance, 7,783 people with other SD, and 193,288 matched controls. A Cox proportional hazard regression was used to compute the risk of AF in people with SD and subgroup of SD, relative to that in people without SD. The AF incidences were 1.21-fold higher (95% CI 1.15-1.27) in the SD cohort, 1.19-fold higher (95% CI 0.91-1.56) in the sleep apnea cohort, 1.26-fold higher (95% CI 1.19-1.34) in the insomnia cohort, 1.15-fold higher (95% CI 1.08-1.22) in the sleep disturbance cohort, and 1.30-fold higher (95% CI 1.11-1.53) in other SDs, than in the control cohort, after age, sex, and comorbidities were adjusted. CONCLUSIONS: This nationwide population-based cohort study indicates a strong relationship between SD and incident AF, and insomnia has a higher impact on AF compared with other SD.

Influenza Vaccination and Risk of Lung Cancer in Patients with Chronic Kidney Disease: A Nationwide, Population-Based Cohort Study.

Chronic kidney disease (CKD) is significantly associated with lung cancer incidence. The aim of this study was to elucidate whether influenza vaccination reduces the incidence of lung cancer in patients with CKD. This cohort study enrolled patients with a record of CKD diagnosis from 2000 to 2012 in Taiwan's National Health Insurance Research Database. Included patients were divided into vaccinated and unvaccinated groups. In total 12,985 patients with CKD were enrolled. Among these patients, 5495 were vaccinated and 7490 were unvaccinated. The risk of lung cancer was significantly lower in the influenza vaccination group after adjusting for age, sex, dialysis status, lung diseases, comorbidities, level of urbanization, and monthly income (adjusted hazard ratio (HR): 0.50, 95% confidence interval (CI; 0.38−0.65), p < 0.05). Lower risk of lung cancer was observed in both sexes, all age groups, dialysis status and co-existed lung diseases. The association between the risk of lung cancer and vaccination appeared to be dose-dependent (adjusted HRs: 0.91 (0.66−1.25), 0.49 (0.34−0.71), and 0.25 (0.17−0.38) for patients who received 1, 2 or 3, and ≥4 vaccinations during the follow-up period, respectively). In conclusion, Influenza vaccination decreased the risk of lung cancer in patients diagnosed with CKD. This potentially protective effect against lung cancer appeared to be dose dependent.

Influenza vaccination and risk of atrial fibrillation in patients with gout: A nationwide population-based cohort study.

Objective: Although influenza vaccination reduces the risk of atrial fibrillation (AF), its protective effect in patients with gout remains unclear. The present study aimed to evaluate the protective effect of influenza vaccination in patients with gout. Methods: A total of 26,243 patients with gout, aged 55 and older, were enrolled from the National Health Insurance Research Database (NHIRD) between 1 January 2001, and 31 December 2012. The patients were divided into vaccinated (n = 13,201) and unvaccinated groups (n = 13,042). After adjusting comorbidities, medications, sociodemographic characteristics, the risk of AF during follow-up period was analyzed. Results: In influenza, non-influenza seasons and all seasons, the risk of AF was significantly lower in vaccinated than in unvaccinated patients (Adjust hazard ratio [aHR]: 0.59, 95% confidence interval [CI]: 0.50-0.68; aHR: 0.50, 95% CI: 0.42-0.63; aHR: 0.55, 95% CI: 0.49-0.62, respectively). In addition, the risk of AF significantly decreased with increased influenza vaccination (aHR: 0.85, 95% CI: 0.69-1.04; aHR: 0.72, 95% CI: 0.60-0.87; aHR: 0.40, 95% CI: 0.33-0.49, after first, 2-3 times, and ≥4 times of vaccination, respectively). Furthermore, sensitivity analysis indicated that the risk of AF significantly decreased after influenza vaccination for patients with different sexes, medication histories, and comorbidities. Conclusions: Influenza vaccination is associated with a lower risk of AF in patients with gout. This potentially protective effect seems to depend on the dose administered.

Association between Stroke Risk and Influenza Vaccination in Patients with Gout: A Nationwide Population-Based Study.

The risk of stroke in patients with gout is high. The effect of vaccines in lowering the stroke risk in patients with gout remains unclear. We retrospectively analyzed 23,949 patients with gout (age ≥ 55 years) from the National Health Insurance Research Database over a 12-year period. The patients were divided into vaccinated (n = 11,649) and unvaccinated groups (n = 12,300). Overall, the vaccinated group had significantly lower risks of all stroke, hemorrhagic stroke, and ischemic stroke than the unvaccinated group (adjusted hazard ratio [aHR], 0.59 and 95% confidence interval [CI], 0.55-0.63; aHR, 0.60 and 95% CI, 0.49-0.73; and aHR, 0.60 and 95% CI, 0.55-0.65, respectively). The association appeared to be dose-dependent for both hemorrhagic and ischemic stroke (hemorrhagic stroke: aHR, 0.81 and 95% CI, 0.61-1.08; aHR, 0.80 and 95% CI, 0.62-1.02; and aHR, 0.37 and 95% CI, 0.28-0.48; ischemic stroke: aHR, 0.83 and 95% CI, 0.74-0.94; aHR, 0.73 and 95% CI, 0.65-0.81; and aHR, 0.42 and 95% CI, 0.38-0.47 for patients vaccinated 1, 2 or 3, and ≥4 times, respectively, during the follow-up period). Patients with a history of atrial fibrillation did not have a lower risk of hemorrhagic stroke even after receiving four vaccinations (aHR, 0.59; 95% CI, 0.25-1.38). Influenza vaccination was associated with a lower risk of all stroke in people with gout, and the association appeared to be dose-dependent.

Machine Learning Analyses Revealed Distinct Arterial Pulse Variability According to Side Effects of Pfizer-BioNTech COVID-19 Vaccine (BNT162b2).

Various adverse events and complications have been attributed to COVID-19 (coronavirus disease 2019) vaccinations, which can affect the cardiovascular system, with conditions such as myocarditis, thrombosis, and ischemia. The aim of this study was to combine noninvasive pulse measurements and frequency domain analysis to determine if the Pfizer-BioNTech COVID-19 vaccine (BNT162b2) vaccination and its accompanying cardiovascular side effects will induce changes in arterial pulse transmission and waveform. Radial blood pressure waveform and photoplethysmography signals were measured noninvasively for 1 min in 112 subjects who visited Shuang-Ho Hospital for a BNT162b2 vaccination. Based on side effects, each subject was assigned to Group N (no side effects), Group CV (cardiac or vascular side effects), Group C (cardiac side effects only), or Group V (vascular side effects only). Two classification methods were used: (1) machine-learning (ML) analysis using 40 harmonic pulse indices (amplitude proportions, phase angles, and their variability indices) as features, and (2) a pulse-variability score analysis developed in the present study. Significant effects on the pulse harmonic indices were noted in Group V following vaccination. ML and pulse-variability score analyses provided acceptable AUCs (0.67 and 0.80, respectively) and hence can aid discriminations among subjects with cardiovascular side effects. When excluding ambiguous data points, the AUC of the score analysis further improved to 0.94 (with an adopted proportion of around 64.1%) for vascular side effects. The present findings may help to facilitate a time-saving and easy-to-use method for detecting changes in the vascular properties associated with the cardiovascular side effects following BNT162b2 vaccination.