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Background: Little is known about the effects of anticoagulation in patients with atrial fibrillation (AF) and left atrial enlargement (LAE)., Methods: Data of patients with AF were retrieved from Chang Gung Research Database during 2007-2016. We excluded patients who were not using oral anticoagulants, used anticoagulants for <30 days, used ≥2 agents concomitantly or switched anticoagulants, had left atrial diameter missing from their data, were aged <65, had received valve surgeries, had mitral stenosis, or had a history of cancer. The primary outcomes were ischemic stroke (IS)/systemic embolism (SE), major bleeding, and death from any cause., Results: We identified 40,777 patients who received a diagnosis of AF. After the exclusion criteria were applied, 6,445 patients remained, 4,922 with LAE, and they were followed up for 2.4 ±1.9 years. The mean age of the patients was 77.32 ± 0.18 in the NOAC group and 76.58 ± 6.91 in the warfarin group (p < 0.0001); 48.24% of patients in the NOAC group and 46.98% of patients in the warfarin group were men (p > 0.05). The mean CHA2DS2-VASc score was 3.26 ± 1.05 in the NOAC group and 3.07 ± 1.12 in the warfarin group (p < 0.0001). The mean HAS-BLED score was 3.87 ± 3.81 in the NOAC group and 3.86 ± 3.80 in the warfarin group (p > 0.05). Furthermore, the mean LA diameter was 4.75 ± 0.63 cm in the warfarin group and 4.79 ± 0.69 cm in the warfarin group (p > 0.05). Among patients with LAE, NOAC was associated with significantly reduced IS/SE events (CRR = 0.63, 95% CI = 0.52-0.77), no difference in major bleeding (CRR = 0.91, 95% CI = 0.78-1.05), and significantly reduced death from any cause (aHR = 0.65, 95% CI = 0.52-0.80) compared with warfarin., Conclusions: In elderly patients with AF and LAE, NOAC was associated with reduced IS/SE and death from any cause compared with warfarin, whereas no difference in major bleeding was observed between these treatments., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To estimate the incidence rate of eye injuries (EI) requiring inpatient and outpatient treatment in Taiwan and compare the epidemiologic characteristics of EI (age, sex, treatment setting, seasonality, occupation, external cause, diagnosis, and surgery) in the years 2000, 2005, 2010, and 2015., Methods: We analyzed four random samples of 1,000,000 beneficiaries each from 2000, 2005, 2010, and 2015 of the Taiwan National Health Insurance Program. The direct age-standardized rate, with 95% confidence interval (CI), was used to compare EI rates for the four calendar years. The chi-square test and chi-square test for trend were used to compare data for the four calendar years., Results: Annual EI incidence rates were between 2.57% in 2000 and 3.28% in 2015. The age-standardized rates were 2.73% (95% CI, 2.70%-2.76%) in 2000, 3.37% (95% CI, 3.33%-3.41%) in 2005, 3.31% (95% CI, 3.28%-3.35%) in 2010, and 3.02% (95% CI, 2.99%-3.06%) in 2015. Manual workers had the highest EI incidence rate, followed by non-manual workers and civil servants. The proportion of EI requiring inpatient treatment declined from 1.34% in 2000 to 0.63% in 2015 (P <0.0001). Analysis of seasonality showed a consistent decrease in February in the four sampling years; however, this decrease in EI was only seen in outpatients, not in EI requiring hospitalization. The proportion of outpatients requiring surgery significantly decreased, from 2.53% in 2000 to 1.2% in 2015 (P<0.0001). However, the proportion of inpatients requiring surgery for EI as the principal diagnosis increased from 69.32% in 2000 to 83.02% in 2015 (P = 0.29), and the proportion of inpatients requiring surgery for EI as a secondary diagnosis increased from 54.86% in 2000 to 71.6% in 2015 (P = 0.0019). Among inpatients with EI, the most common cause of EI was a traffic accident (44.79%, especially motorcycles), followed by falls (9.75%) and homicide (6.05%)., Conclusion: In Taiwan, the annual EI incidence rate slightly increased from 2000 to 2005 and then decreased through 2015. The proportion of EI patients requiring hospitalization decreased from 1.34% in 2000 to 0.63% in 2015, but the percentage of inpatients requiring surgery increased. Traffic accidents (especially those involving motorcyclists) remained the predominant external cause of EI requiring hospitalization during the study period., Competing Interests: The authors have declared that no competing interests exist.

Background: Patients with chronic obstructive pulmonary disease (COPD) less often receive β-blockers after acute myocardial infarction (AMI). This may influence their outcomes after AMI. This study evaluated the efficacy of β-blockers after AMI in patients with COPD, compared with non-dihydropyridine calcium channel blockers (NDCCBs) and absence of these two kinds of treatment., Methods and Results: We conducted a nationwide population-based cohort study using data retrieved from Taiwan National Health Insurance Research Database. We collected 28,097 patients with COPD who were hospitalized for AMI between January 2004 and December 2013. After hospital discharge, 24,056 patients returned to outpatient clinics within 14 days (the exposure window). Those who received both β-blockers and NDCCBs (n = 302) were excluded, leaving 23,754 patients for analysis. Patients were classified into the β-blocker group (n = 10,638, 44.8%), the NDCCB group, (n = 1,747, 7.4%) and the control group (n = 11,369, 47.9%) based on their outpatient prescription within the exposure window. The β-blockers group of patients had lower overall mortality risks (adjusted hazard ratio [95% confidence interval]: 0.91 [0.83-0.99] versus the NDCCB group; 0.88 [0.84-0.93] versus the control group), but the risk of major adverse cardiac events within 1 year was not statistically different. β-blockers decreased risks of re-hospitalization for COPD and other respiratory diseases by 12-32%., Conclusions: The use of β-blockers after AMI was associated with a reduced mortality risk in patients with COPD. β-blockers did not increase the risk of COPD exacerbations., Competing Interests: The authors have declared that no competing interests exist.

Background: Splenic abscess is rare but has mortality rates as high as 14% even with recent improvements in management. Early and appropriate intervention may improve patient outcomes, yet at present there is no identified method that can predict mortality risk rapidly and accurately for emergency physicians, surgeons, and intensivists to decide on the ideal course of action., Objective: This study aims to evaluate the performance of Mortality in Emergency Department Sepsis Score (MEDS), Modified Early Warning Score (MEWS), Rapid Emergency Medicine Score (REMS) and Rapid Acute Physiology Score (RAPS) for predicting the mortality risk of adult splenic abscess patients. This will expedite decision making in the emergency department (ED) to increase survival rates and help avoid unnecessary splenectomies., Methods: Data of 114 adult patients admitted to the EDs of 4 research and training hospitals who had undergone an abdominal contrast CT scan and diagnosed with splenic abscess between Jan 2000 and April 2015 were analyzed. The MEDS, MEWS, REMS, and RAPS and their corresponding mortality risks were calculated, with their abilities to predict patient mortality assessed through receiver operating characteristic curve analysis and calibration analysis., Results: MEDS was found to be the best performing scoring system across all indicators, with sensitivity, specificity, and accuracy of 92.86%, 88.00%, and 88.60% respectively; its area under curve for AUROC analysis was 0.92. With a cutoff value of 8, negative predictive value of MEDS was 98.88%., Conclusion: Our series is the largest multicenter study in adult ED patients with splenic abscess. The results from the present study show that MEDS is superior to MEWS, REMS and RAPS in predicting mortality, thus allowing earlier detection of critically ill adult ED splenic abscess patients. Therefore, we recommend that MEDS be used for predicting severity of illness and risk stratification in these patients.

Objectives: The risk of herpes zoster (HZ) between patients with psoriasis receiving and not receiving systemic therapy has received increasing attention. This study investigated the association of psoriasis with the risk of HZ., Methods: We conducted a population-based retrospective cohort study by using the Taiwan National Health Insurance Research Database. The psoriasis cohort consisted of 4077 patients with newly diagnosed psoriasis between 2000 and 2006. Each patient with psoriasis was frequency-matched with four people without psoriasis, by sex, age and index year. (nonpsoriasis cohort; 16308 subjects). Patients who received systemic therapy were classified as having severe psoriasis, whereas those who did not receive systemic therapy were classified as having mild psoriasis. The Cox proportional hazards regression analysis was conducted to estimate the association between psoriasis and HZ risk., Results: The overall incidence density rate of HZ in the psoriasis cohort than in the nonpsoriasis cohort (4.50 vs. 3.44 per 1,000 person-years), with a multivariable Cox proportional hazards model measured adjusted HR of 1.29 [95% confidence interval (CI) = 1.07-1.56]. In additional, compared with the nonpsoriasis cohort, the risk of HZ was higher in the severe psoriasis cohort than in the nonpsoriasis cohort (adjusted hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.15-2.27). The comparison between psoriasis and nonpsoriasis cohorts revealed a greatest magnitude risk of HZ in women (adjusted HR, 1.36; 95% CI, 1.04-1.79), study participants in the age group of 20-39 years (adjusted HR, 1.77; 95% CI, 1.17-2.66), and study participants without any comorbidities (adjusted HR, 1.37; 95% CI, 1.02-1.84)., Conclusions: Our results suggest that psoriasis is associated with an increased risk of HZ, which involves differences in sex and age. Although systemic therapy may have a major role in the risk of HZ, the intrinsic factors of psoriasis cannot be excluded.

Objective: Though the risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA) has been established in Western population, little is known about the risk in Chinese people with RA. Our objective was to estimate the risk of CVD in Chinese people with RA using hospital medical records data., Methods: The inpatients medical record database 2005-2015 of Sichuan provincial people's hospital was examined. All individuals with a primary diagnosis of RA were included as cases, and those of osteoarthritis (OA) were included as controls, which consisted of the unmatched dataset. Then, RA cases and OA controls were matched by sex and age at 1:1 ratio, forming the matched dataset. The morbidity of CVD (including ischemia heart disease (IHD), congestive heart failure (CHF), et al), stroke and arthrosclerosis were extracted from the database, so as the demographic data and comorbidities related to CVD. Multiple logistic regression analysis was used to estimate the risk of CVD in RA adjusted for demographics and comorbidities using the unmatched dataset. Sensitivity analysis was conducted 1) considering interaction terms between RA and comorbidities, and 2) using multivariable conditional logistic regression for the matched dataset., Results: The unmatched dataset comprised of 1824RA cases and 1995 OA controls and the matched dataset comprised of 1022 pairs of sex and age matched RA and OA patients. RA exhibited increased odds of prevalent CVD compared with OA, and the adjusted ORs (95%CIs) for CVD, stroke, IHD, CHF, and atherosclerosis were1.86(1.42-2.43), 1.11(0.71-1.74), 1.47(0.97-2.24), 2.09(1.03-4.22), and 2.49 (1.97-3.13), respectively, and was 2.26 (1.29-3.96)for IHD further adjusted for interaction term. The matched dataset analysis found similar results., Conclusions: Chinese people with RA were approximated 2 times more likely to have CVD, IHD, CHF and atherosclerosis compared with those with OA. The findings justified the need of further longitudinal study to establish the causal-relationship between RA and CVD and to estimate the precise risk in this population.

Streptococcus pyogenes (group A Streptococcus; GAS) causes clinical diseases, including pharyngitis, scarlet fever, impetigo, necrotizing fasciitis and streptococcal toxic shock syndrome. A number of group A streptococcus vaccine candidates have been developed, but only one 26-valent recombinant M protein vaccine has entered clinical trials. Differing from the design of a 26-valent recombinant M protein vaccine, we provide here a vaccination using the polyvalence epitope recombinant FSBM protein (rFSBM), which contains four different epitopes, including the fibronectin-binding repeats domain of streptococcal fibronectin binding protein Sfb1, the C-terminal immunogenic segment of streptolysin S, the C3-binding motif of streptococcal pyrogenic exotoxin B, and the C-terminal conserved segment of M protein. Vaccination with the rFSBM protein successfully prevented mortality and skin lesions caused by several emm strains of GAS infection. Anti-FSBM antibodies collected from the rFSBM-immunized mice were able to opsonize at least six emm strains and can neutralize the hemolytic activity of streptolysin S. Furthermore, the internalization of GAS into nonphagocytic cells is also reduced by anti-FSBM serum. These findings suggest that rFSBM can be applied as a vaccine candidate to prevent different emm strains of GAS infection.

Group A streptococcus (GAS) is an important human pathogen that produces several extracellular exotoxins to facilitate invasion and infection. Streptococcal pyrogenic exotoxin B (SPE B) has been demonstrated to be an important virulence factor of GAS. Our previous studies indicate that SPE B cleaves complement 3 (C3) and inhibits the activation of complement pathways. In this study, we constructed and expressed recombinant fragments of SPE B to examine the C3-binding site of SPE B. Using enzyme-linked immunosorbent assays and pull-down assays, we found that the C-terminal domain, containing amino-acid residues 345-398, of SPE B was the major binding site of human serum C3. We further identified a major, Ala376-Pro398, and a minor C3-binding motif, Gly346-Gly360, that both mediated the binding of C3 complement. Immunization with the C3-binding motifs protected mice against challenge with a lethal dose of non-invasive M49 strain GAS but not invasive M1 strains. To achieve higher efficiency against invasive M1 GAS infection, a combination of synthetic peptides derived from C-terminal epitope of streptolysin S (SLSpp) and from the major C3-binding motif of SPE B (PP6, Ala376-Pro398) was used to elicit specific immune response to those two important streptococcal exotoxins. Death rates and the severity of skin lesions decreased significantly in PP6/SLSpp-immunized mice that were infected with invasive M1 strains of GAS. These results indicate a combination of the C3-binding motif of SPE B and the protective epitope of SLS could be used as a subunit vaccine against invasive M1 strains group A streptococcal infection.

Objectives: The aim of this study was to estimate the risk of hyperuricaemia and gout in people with hypothyroid or hyperthyroid status., Methods: This study analyzed data from individuals who participated in health screening programs at Chang Gung Memorial Hospital in northern Taiwan (2000-2010). Participants were categorized as having euthyroid, hypothyroid, or hyperthyroid status according to their thyroid-stimulating hormone (TSH) levels. Multinomial logistic regression models were used to calculate the odds ratios (95% CI) for hyperuricaemia and gout in participants with thyroid dysfunction compared to euthyroid participants., Results: A total of 87,813 (euthyroid, 83,502; hypothyroid, 1,460; hyperthyroid, 2,851) participants were included. The prevalence of hyperuricaemia was higher in hyperthyroid subjects (19.4%) than in euthyroid subjects (17.8%) but not in hypothyroid subjects (19.3%). The prevalence of gout was significantly higher in both hypothyroid (6.0%) and hyperthyroid (5.3%) subjects than in euthyroid subjects (4.3%). In men, hypothyroid or hyperthyroid status was not associated with hyperuricaemia. However, hypothyroid or hyperthyroid status was associated with ORs (95% CI) of 1.47 (1.10-1.97) and 1.37 (1.10-1.69), respectively, for gout. In women, hypothyroid status was not associated with hyperuricaemia or gout. However, hyperthyroid status was associated with ORs (95% CI) of 1.42 (1.24-1.62) for hyperuricaemia and 2.13 (1.58-2.87) for gout., Conclusions: Both hyperthyroid and hypothyroid status were significantly associated with gout and weakly associated with hyperuricaemia. A thyroid function test for gout patients may by warranted.

Higher soluble CD4 (sCD4) levels in serum have been detected in patients of infectious and chronic inflammatory diseases. However, how and why sCD4 is produced remains poorly understood. We establish sensitive ELISA and WB assays for sCD4 detection in conditioned medium of in vitro cell culture system and serum of chronic inflammatory patients. Serum samples from patients with systemic lupus erythematosus (SLE) (n = 79), rheumatoid arthritis (RA) (n = 59), ankylosing spondylitis (AS) (n = 25), gout (n = 31), and normal controls (n = 99) were analyzed using ELISA for sCD4 detection. Results from each assay were analyzed by the Kruskal-Wallis test. Dunn's multiple comparison post-test was then applied between groups. We confirm that cells expressing exogenous CD4 produce sCD4 in a constitutive and PMA-induced manner. Importantly, sCD4 production in a heterologous expression system is inhibited by GM6001 and TAPI-0, suggesting receptor shedding by matrix metalloproteinase (MMP)-like proteinases. Moreover, similar findings are recapitulated in human primary CD4(+) T cells. Finally, we show that serum sCD4 levels are increased in patients of chronic inflammatory diseases including RA and SLE, but not in those with gout. Intriguingly, sCD4 levels in RA patients are correlated positively with the disease activities and higher sCD4 levels seem to associate with poor prognosis. Taken together, we conclude that CD4 is shed from cell surface by a MMP-like sheddase and sCD4 level is closely related with the inflammatory condition in certain chronic diseases. Hence, sCD4 might be considered an important parameter for RA disease progression with potential diagnostic importance.

Streptococcal pyrogenic exotoxin B (SPE B), a cysteine protease, is an important virulence factor in group A streptococcal (GAS) infection. SPE B binds and cleaves antibody isotypes and further impairs the immune system by inhibiting complement activation. In this study, we examined the antibody-binding site of SPE B and used it to block SPE B actions during GAS infection. We constructed different segments of the spe B gene and induced them to express different recombinant fragments of SPE B. Using an enzyme-linked immunosorbent assay (ELISA), we found that residues 345-398 of the C-terminal domain of SPE B (rSPE B(345-398)), but not the N-terminal domain, was the major binding site for antibody isotypes. Using a competitive ELISA, we also found that rSPE B(345-398) bound to the Fc portion of IgG. The in vitro functional assays indicate that rSPE B(345-398) not only interfered with cleavage of antibody isotypes but also interfered with SPE B-induced inhibition of complement activation. Immunization of BALB/c mice using rSPE B(345-398) was able to induce production of a high titer of anti-rSPE B(345-398) antibodies and efficiently protected mice from GAS-induced death. These findings suggest that SPE B uses its C-terminal domain to bind the Fc portion of IgG and that immunization of mice with this binding domain (rSPE B(345-398)) could protect mice from GAS infection.

Aims: To isolate phages against extensively drug resistant Acinetobacter baumannii (XDRAB) and characterize the highest lytic capability phage as a model to evaluate the potential on phage therapy., Methods and Results: Eight phages were isolated from hospital sewage and showed narrow host spectrum. Phage φkm18p was able to effectively lyse the most XDRAB. It has a dsDNA genome of 45 kb in size and hexagonal head of about 59 nm in diameter and no tail. Bacterial population decreased quickly from 10(8) CFU ml(-1) to 10(3) CFU ml(-1) in 30 min by φkm18p. The 185 kDa lysis protein encoded by φkm18p genome was detected when the extracted protein did not boil before SDS-PAGE; it showed that the lysis protein is a complex rather than a monomer. Phage φkm18p improved human lung epithelial cells survival rates when they were incubated with A. baumannii. Combination of phages (φkm18p, φTZ1 and φ314) as a cocktail could lyse all genotype-varying XDRAB isolates., Conclusion: Infections with XDRAB are extremely difficult to treat and development of a phage cocktails therapy could be a therapeutic alternative in the future. Phage φkm18p is a good candidate for inclusion in phage cocktails.