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Cord blood transplantation (CBT) provides a treatment scheme for hematologic diseases and leukemia in both children and adults. However, adverse reactions and transplantation-related death may still occur in patients receiving CBT even when donor and recipient have fully matched HLA in high-resolution HLA typing analysis. Single nucleotide polymorphisms (SNPs) of HLA-related and unrelated genes are known to associate with disease status of patients with unrelated stem cell transplantation. In this study, the genomic regions ranging from 500 base pairs upstream to 500 base pairs downstream of the eight SNPs that were reported as transplantation determinants by Petersdorf et al. were analyzed to evaluate whether genetic variants were associated with the survival status of patients, and the risk for severe (grades 3–4) graft-versus-host disease (GVHD) or cytomegalovirus (CMV) infection/reactivation. The analyses were performed in the mode of recipient genotype, donor genotype, and recipient-donor mismatching, respectively. By analysis of sixty-five patients and their HLA-matched unrelated donors, we found that five SNPs were associated with patient survival which included the recipient genotype with SNPs of rs107822 in the RING1 gene, and rs2070120, rs17220087 and rs17213693 in the HLA-DOB gene; and the recipient-donor mismatching with SNPs of rs9282369 in HLA-DOA gene, and rs2070120, rs17220087 and rs17213693 in the HLA-DOB gene. Five SNPs were associated with the risk for severe GVHD which included the donor genotype with SNPs of rs213210 and rs2523675; the recipient genotype with SNPs of rs9281491 in the HCP5 gene; and the recipient-donor mismatching with SNPs of rs209130 in the TRIM27 gene, and rs986522 in the COL11A2 gene. Six SNPs were related to the risk for CMV infection/reactivation which included the donor genotype with SNPs of rs435766, rs380924, and rs2523957; and the recipient-donor mismatching with SNPs of rs2070120, rs17220087, and rs17213693 in the HLA-DOB gene; and rs435766 and rs380924 in the MICD gene. This study provides the basis for larger analyses and if the results are confirmed, a way of selecting better unrelated CBT candidate donors.

Background: Previous studies have reported that electroacupuncture (EA) induces a glucose-lowering effect by improving insulin resistance (IR) and reduces plasma free fatty acid (FFA) levels in rats with steroid-induced insulin resistance (SIIR). In addition, EA can activate cholinergic nerves and stimulate endogenous opioid peptides to lower plasma glucose in streptozotocin-induced hyperglycemic rats. The aim of this study was to investigate the glucose-lowering effects of 15 Hz EA at bilateral ST36 in combination with acarbose (ACA). We hypothesized that EA combined with ACA would produce a stronger glucose-lowering effect than ACA alone. Methods: In this study, normal Wistar rats and SIIR rats were randomly divided into two groups: ACA and ACA + EA. To explore the potential mechanisms underlying the glucose-lowering effect, plasma FFA/insulin and insulin transduction signal pathway proteins were assayed. Results: Combined ACA + EA treatment had a greater glucose-lowering effect than ACA alone in normal Wistar rats (−45% ± 3% vs −19% ± 3%, p Conclusion: Combined EA and ACA therapy had a greater glucose-lowering effect than ACA monotherapy; this combined therapy could be more effective at improving IR in SIIR rats, which may be related to a reduction in plasma FFA levels and an elevation of insulin signaling proteins. Whether this combined therapy has an effect in type 2 diabetes mellitus (T2DM) patients still needs to be explored.

To avoid graft rejection, the hematopoietic stem cells with matched classical human leukocyte antigen (HLA) alleles are the primary choice for clinical allogeneic transplantation. However, even if the fully HLA-matched hematopoietic stem cells are used for transplantation, some patients still have poor prognosis after hematopoietic stem cell transplantation (HSCT), suggesting that the HLA system was not the only determinant of the outcomes of HSCT. In this study, we investigated whether the single-nucleotide polymorphisms (SNPs) of the co-stimulatory genes within non-HLA regions were related to the outcomes of HSCT. The genomic DNAs of 163 patients who had acute leukemia and received HSCT and their respective donors were collected for analysis. Thirty-four SNPs located in the four co-stimulatory genes including cytotoxic T-lymphocyte associated protein 4 (CTLA4), CD28, tumor necrosis factor ligand superfamily 4 (TNFSF4), and programmed cell death protein 1 (PDCD1) were selected to explore their relationship with the adverse outcomes after transplantation, including mortality, cytomegalovirus infection, graft-versus-host disease, and relapse. Our results revealed that nine SNPs in the CTLA4 gene, five SNPs in the PDCD1 gene, two SNPs in the TNFSF4 gene, and four SNPs in the CD28 gene were significantly associated with the occurrence of adverse outcomes post-HSCT. These SNPs may play important roles in immune response to allografts post-HSCT and can be the targets for developing strategy to identify appropriate donors.

Disease relapse occurs in patients with leukemia even hematopoietic stem cell transplantation (HSCT) was performed with human leukocyte antigen (HLA)-matched donors. As revealed previously by Petersdorf et al., there are nine single nucleotide polymorphisms (SNPs) located in the HLA region that potentially modulate the efficacy of HSCT. In this study, we investigated whether or not the genomic variants 500 base pairs flanking the nine transplantation-related SNPs were related to the risk of post-HSCT relapse for patients with leukemia (n = 141). The genomic DNAs collected from 85 patients with acute myeloid leukemia (AML), 56 patients with acute lymphocytic leukemia (ALL), and their respective HLA-matched donors were subject to SNPs analysis, conferred by the mode of mismatch between donor-recipient pair or by recipient or donor genotype analysis. Seven SNPs were revealed to associate with the risk of relapse post-HSCT. For patients with AML, the increased risk of post-HSCT relapse was associated with the donor SNP of rs111394117 in the intron of NOTCH4 gene, and the recipient SNPs of rs213210 in the ring finger protein 1 (RING1) gene promoter, and rs17220087 and rs17213693 in the intron of HLA-DOB gene. For patients with ALL, the increased risk of post-HSCT relapse was associated with the donor SNP of rs213210 in the RING1 gene promoter, and the recipient SNPs of rs79327197 in the HLA-DOA gene promoter, rs2009658 in the telomeric end of lymphotoxin-alpha (LTA) gene, rs17220087 and rs17213693 in the intron of HLA-DOB gene, and rs2070120 in the 3′-UTR of HLA-DOB gene. This study sheds new insight into selecting better candidate donors for performing HSCT in patients with AML and ALL.

The FloTrac system is a system for cardiac output (CO) measurement that is less invasive than the pulmonary artery catheter (PAC). The purposes of this study were to (1) compare the level of agreement and trending abilities of CO values measured using the fourth version of the FloTrac system (CCO-FloTrac) and PAC-originated continuous thermodilution (CCO-PAC) and (2) analyze the inadequate CO-discriminating ability of the FloTrac system before and after cardiopulmonary bypass (CPB). Fifty patients were included. After exclusion, 32 patients undergoing cardiac surgery with CPB were analyzed. All patients were monitored with a PAC and radial artery catheter connected to the FloTrac system. CO was assessed at 10 timing points during the surgery. In the Bland–Altman analysis, the percentage errors (bias, the limits of agreement) of the CCO-FloTrac were 61.82% (0.16, − 2.15 to 2.47 L min) and 51.80% (0.48, − 1.97 to 2.94 L min) before and after CPB, respectively, compared with CCO-PAC. The concordance rates in the four-quadrant plot were 64.10 and 62.16% and the angular concordance rates (angular mean bias, the radial limits of agreement) in the polar-plot analysis were 30.00% (17.62°, − 70.69° to 105.93°) and 38.63% (− 10.04°, − 96.73° to 76.30°) before and after CPB, respectively. The area under the receiver operating characteristic curve for CCO-FloTrac was 0.56, 0.52, 0.52, and 0.72 for all, ≥ ± 5, ≥ ± 10, and ≥ ± 15% CO changes (ΔCO) of CCO-PAC before CPB, respectively, and 0.59, 0.55, 0.49, and 0.46 for all, ≥ ± 5, ≥ ± 10, and ≥ ± 15% ΔCO of CCO-PAC after CPB, respectively. When CO

To identify the association between metabolites and muscle mass in 305 elderly Taiwanese subjects, we conducted a multivariate analysis of 153 plasma samples. Based on appendicular skeletal muscle mass index (ASMI) quartiles, female and male participants were divided into four groups. Quartile 4 (Men: 5.67±0.35, Women: 4.70±0.32 Kg/m2) and quartile 1 (Men: 7.60±0.29, Women: 6.56±0.53 Kg/m2) represented low muscle mass and control groups, respectively. After multivariable adjustment, except for physical function, we found that blood urea nitrogen, creatinine, and age were associated with ASMI in men. However, only triglyceride level was related to ASMI in women. The multiple logistic regression models were used to analyze in each baseline characteristic and metabolite concentration. After the adjustment, we identify amino acid-related metabolites and show that glutamate levels in women and alpha-aminoadipate, Dopa, and citrulline/ornithine levels in men are gender-specific metabolic signatures of muscle mass loss.

It remains unclear whether infection events before entering end stage renal disease (ESRD) have a long-term negative impact on patients with advanced chronic kidney disease (CKD) who survive to permanent dialysis. We enrolled 62,872 patients with advanced CKD who transitioned to maintenance dialysis between January 1, 2004 and December 31, 2013. We used multivariable Cox as well as Fine and Gray models to determine the association of pre-dialysis infection exposure with all-cause mortality after starting dialysis. Compared with no infection during advanced CKD, the presence of infection exposure during that period was independently associated with a higher risk of all-cause mortality in the first year of dialysis (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.27–1.42) and also during the entire follow-up period (HR 1.19, 95% CI 1.16–1.22). The increased risks of all-cause mortality increased incrementally with higher annual number of infections during advanced CKD. Similar results were found for all other adverse outcomes, e.g. post-ESRD infection-related hospitalization and major cardiac and cerebrovascular events. In conclusion, infection events during advanced CKD was associated with increased risks of adverse outcomes after dialysis has been started. Timely interventions in such a vulnerable group may help attenuate these risks.

Purpose Patients receiving extracorporeal membrane oxygenation (ECMO) commonly develop acute kidney injury (AKI) and frequently require continuous renal replacement therapy (CRRT). The impact of different CRRT modalities on survival in patients receiving ECMO remains unclear. Materials and methods Using claims data from Taiwan's National Health Insurance Research Database, a total of 1077 patients who received ECMO and either continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodialysis (CVVHD) for AKI were identified. Inverse probability of treatment weighting was applied using propensity scores to balance the baseline covariates of the two groups. The primary outcome was in-hospital morality. Results We identified 1077 patients (mean age 57.9; 71.8% men). Postcardiotomy shock (49.2%) was the most frequently reported indication for ECMO. The CVVH group had a lower risk of in-hospital mortality (68.4% vs. 76.9%; odds ratio 0.65; 95% confidence interval [CI] 0.50–0.85) compared with the CVVHD group. The CVVH group also had a shorter mean ICU stay compared with the CVVHD group (mean difference −4.59 days, 95% CI −9.15 to −0.03 days). Conclusion Our results suggest that compared with CVVHD, CVVH may be associated with a lower risk of in-hospital mortality in patients with AKI who receive ECMO.

Genetic profiles of hepatitis C virus (HCV)-associated mixed cryoglobulinemia (MC) in Asians remain elusive. A 10-year prospective cohort study was conducted with 1043 consecutive HCV Ab-positive Taiwanese surveyed with 13 single nucleotide polymorphisms (SNPs). Of 1043, 589 (56.5%) had baseline MC, 934 (89.5%) had positive HCV RNA, 796 completed anti-HCV therapy, and 715 had sustained virological responses (SVRs). SNP associations were surveyed withgenotypic, allelic, trend, permutation and multivariate analyses. At baseline, higher male sex and MC rates were noted in HCV RNA-positive than RNA-negative patients, higher female sex and positive HCV RNA rates but lower HCV RNA levels were noted in patients with than those without MC. Baseline associations were: HLA II-rs9461776 A allele, IFNL3-rs12979860 T allele, SERPINE1-rs6976053 C allele and MC with HCV RNA positivity, IFNL3-rs12979860 C allele, ARNTL-rs6486122 T allele and HCV RNA positivity with baseline MC. In SVR patients, RETN-rs1423096 C allele and SERPINE1-rs6976053 T allele were associated with 24-week and 10-year post-therapy MC, respectively. Conclusions: HCV RNA, IFNL3-rs12979860 and ARNTL-rs6486122 were associated with baseline MC, RETN-rs1423096 and SERPINE1-rs6976053 were associated with short- and long-term post-therapy MC in SVR patients, respectively. Links with HCV RNA and immune-associated SNPs suggest MC an immune reaction to expel HCV.

Background and Purpose— We investigated whether use of acupuncture within a 3-month poststroke period after hospital discharge is associated with reduced risk of depression. Methods— This cohort study included 16 046 patients aged ≥18 years with an initial hospitalization for stroke during 2000 and 2012 in the claims database of a universal health insurance program. Patients who had received acupuncture therapies within 3 months of discharge were defined as acupuncture users (n=1714). All patients were followed up for incidence of depression until the end of 2013. We assessed the association between use of acupuncture and incidence of depression using Cox proportional hazards models in all subjects and in propensity score–matched samples consisting of 1714 pairs of users and nonusers. Results— During the follow-up period, the incidence of depression per 1000 person-years was 11.1 and 9.7 in users and nonusers, respectively. Neither multivariable-adjusted Cox models (hazard ratio, 1.04; 95% confidence interval, 0.84–1.29) nor the propensity score-matching model (hazard ratio, 1.06; 95% confidence interval, 0.79–1.42) revealed an association between use of acupuncture and incidence of depression. Conclusions— In patients admitted to hospital for stroke, acupuncture therapy within 3 months after discharge was not associated with subsequent incidence of depression.

To determine the relationships between exposure to environmental contaminants in water and chronic kidney disease (CKD), we investigated the associations of 61 water attributes with the prevalence of CKD and End-Stage Renal Disease (ESRD) using data from 2005 to 2011 from all 22 counties and cities in the main island of Taiwan. We acquired patient information from the Taiwan Longitudinal Health Insurance Database to calculate the age-standardized CKD and ESRD prevalence rates and linked the patients&rsquo, residences to the water quality monitoring data, which were sampled periodically for a total of over 45,000 observations obtained from the Taiwan Environmental Water Quality Information Database. The association analysis adjusting for gender, age, and annual effects showed that the zinc (Zn), ammonia, chemical oxygen demand (COD), and dissolved oxygen in rivers were weakly correlated with CKD (&tau, = 0.268/0.250/0.238/&minus, 0.267, p = 6.01&times, 10&minus, 6/2.52&times, 5/6.05&times, 5/3.30&times, 5, respectively), but none for ESRD. The importances of Zn and COD in rivers were also demonstrated in a CKD regression model. Moreover, an unusually high CKD prevalence was related to arsenic contamination in groundwater. A further prospective cohort study would improve our understanding of what level of environmental water with risky properties could affect the development of CKD.

The prevalence of depression in patients with cancer is high, especially for patients with advanced cancer. In this study, we evaluated the prevalence of depression in prostate cancer patients in Taiwan and the association between depression and mortality in prostate cancer. This study included 1101 newly diagnosed patients with prostate cancer. We tracked the medical information of these patients from diagnosis until the end of 2012. Patients were divided into two groups according to presence or absence of depression diagnosis, and were further divided into three stages by initial treatments: localized or locally advanced, metastatic, and castration-resistant prostate cancer. Of 1101 participants, 267 (24.3%) had depression. By the end of the follow-up period (M = 8.30 ± 3.12 years), 77 (28.8%) patients in the depression group and 194 (23.3%) in the non-depressed group died. Depression was associated with higher mortality risk, (aHR 1.37, 95% CI [ 1.04–1.80], p value 0.01). Patients in the metastatic prostate cancer group with depression had a significantly higher mortality risk compared to the non-depressed group, (aHR, 1.49, 95% CI [1.05–2.11], p value 0.02). The impact of depression on mortality risk was not significant in either the localized or locally advanced or the castration-resistant prostate cancer groups. Our study showed that depression is related to an increased mortality risk for patients with prostate cancer, especially for metastatic prostate cancer. These results indicate that urologists should pay attention to the mood and psychiatric disorders of patients with prostate cancer.

Background: A beneficial effect of a ketoanalogue-supplemented low-protein diet (sLPD) in postponing dialysis has been demonstrated in numerous previous studies. However, evidence regarding its effect on long-term survival is limited. Our study assessed the long-term outcomes of patients on an sLPD after commencing dialysis. Methods: This retrospective study examined patients with new-onset end-stage renal disease with permanent dialysis between 2001 and 2013, extracted from Taiwan&rsquo, s National Health Insurance Research Database. Patients who received more than 3 months of sLPD treatment in the year preceding the start of dialysis were extracted. The outcomes studied were all-cause mortality, infection rate, and major cardiac and cerebrovascular events (MACCEs). Results: After propensity score matching, the sLPD group (n = 2607) showed a lower risk of all-cause mortality (23.1% vs. 27.6%, hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.70&ndash, 0.84), MACCEs (19.2% vs. 21.5%, HR 0.86, 95% CI 0.78&ndash, 0.94), and infection-related death (9.9% vs. 12.5%, HR 0.76, 95% CI 0.67&ndash, 0.87) than the non-sLPD group did. Conclusion: We found that sLPD treatment might be safe without long-term negative consequences after dialysis treatment.

Background Although urinary neutrophil gelatinase-associated lipocalin (NGAL) has emerged as a promising biomarker for the early detection of kidney injury, previous studies of adult patients who underwent cardiac surgery have reported only moderate discrimination. The age, creatinine, and ejection fraction (ACEF) score is a preoperative validated risk model with satisfactory accuracy for predicting AKI following cardiac surgery. It remains unknown whether combining preoperative risk assessment through ACEF scores followed by urinary NGAL test in a population of high-risk individuals is an optimal approach with improved predictive performance. Material and methods A total of 177 consecutive patients who underwent cardiac surgery were enrolled. Clinical characteristics, prognostic model scores, and outcomes were assessed. Urinary NGAL were examined within 6 hours after cardiac surgery. Patients were stratified according to preoperative ACEF scores, and comparisons were made using the area under the receiver operator characteristic curve (AUROC) for the prediction of AKI. Results A total of 45.8% (81/177) of the patients had AKI. As expected, patients with ACEF scores ≥ 1.1 were older and more likely to have class III or IV heart failure. They were also more likely to have diabetes mellitus, myocardial infarction, and peripheral arterial disease. Urinary NGAL alone moderately predicted AKI, with an AUROC of 0.732. Risk stratification by ACEF scores ≥ 1.1 substantially improved the AUROC of urinary NGAL to 0.873 (95% confidence interval, 0.784–0.961; P < .001). Conclusions Risk stratification by preoperative ACEF scores ≥ 1.1, followed by postoperative urinary NGAL, provides more satisfactory risk discrimination than does urinary NGAL alone for the early detection of AKI after cardiac surgery. Future studies should investigate whether this strategy could improve the outcomes and cost-effectiveness of care in patients undergoing cardiac surgery.

INTRODUCTION Phosphate level is often deranged during acute illness, regardless of the presence of kidney injury or not. A few studies described that hypophosphatemia may associated with outcome in patients admitted to the burn unit, but the literatures for hyperphosphatemia is limited. Our study aims to evaluate if hyperphosphatemia, one of the sign of severe tissue damage or kidney injury, will associate with mortality of patients with severe burns. MATERIALS AND METHODS The study was a post hoc analysis of prospectively collected data from patients admitted to the burn unit between September 2006 and December 2011. Patients were stratified into normophosphatemic or hyperphosphatemic group by baseline plasma phosphate level. The primary endpoint is 90-day mortality. RESULTS Total 301 patients were included (hyperphosphatemia: n = 52; normophosphatemia: n = 249). The hyperphosphatemic group had lower Glasgow Coma Scale, mean arterial blood pressure, hemoglobin level, albumin, and higher TBSA of burns, APACHE II score, ABSI score, Acute kidney injury (AKI), and creatinine. The 90-day mortality was higher in the hyperphosphatemic group than in the normal group (53.8% vs 18.1%, P < .001) and this difference was still significant when adjusting for several confounding factors (hazard ratio, 2.05; 95% CI, 1.17-3.59). Multivariable Cox analysis showed risk factors of mortality included TBSA of burns, hyperphosphatemia, reduced urine output, and APACHE II score. CONCLUSIONS Our study found in addition to TBSA of burns and inhalation injury, baseline hyperphosphatemia in patients with severe burns is also associated with higher mortality.

Background Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and SJS/TEN overlap syndrome are severe drug-induced cutaneous adverse reactions with high mortality. Acute kidney injury (AKI) was a common complication in an SJS/TEN group and noted as an independent risk factor for mortality in patients with SJS/TEN. To determine whether AKI staging can predict the outcome of patients with SJS/TEN, we compared the discriminative power of an AKI KDIGO staging system with that of SCROTEN, APACHE II, APACHE III, and SOFA. Materials and methods We retrospectively analyzed the data of 75 patients who were diagnosed with SJS, TEN, or SJS/TEN overlap syndrome at a tertiary care university hospital between January 1, 2011 and December 31, 2014. The baseline characteristics, biochemical analysis data, medication use, and outcomes of the patients were assessed, and the discriminative ability for predicting mortality was determined for each prognostic model. Results Of the 75 patients, 23 (30.7%) had AKI, of whom 13 (56.5%) died during the index admission. Of the prognostic risk models analyzed, the KDIGO staging system showed similar discriminative ability in predicting in-hospital mortality as did the other models. In addition, combining KDIGO with other scoring systems yielded significantly more accurate risk prediction for in-hospital mortality compared with the other individual scores alone, as measured by net reclassification index. The patients with KDIGO stages 2 and 3 exhibited a significantly lower 1-year survival rate than did those with KDIGO stages 0 and 1. Conclusion AKI KDIGO staging has good discriminative ability and is easy to utilize for predicting mortality.

Background Acute respiratory distress syndrome (ARDS) is a life-threatening medical condition. Extracorporeal membrane oxygenation (ECMO) is a salvage therapy for patients with ARDS and refractory hypoxia. This study compared the characteristics and outcomes of ARDS patients who did or did not receive ECMO matched with Acute Physiology and Chronic Health Evaluation II (APACHE II) score and age. Methods This retrospective, case-control study enrolled patients with ARDS admitted to the intensive care unit of a tertiary referral hospital between January 2007 and December 2012. Overall, 216 patients with ARDS—81 receiving ECMO (ECMO group) and 135 not receiving ECMO (non-ECMO group)—were enrolled in this study. Patients were paired when the difference in their APACHE II scores was within 3 points and their age difference was 3 years. In total, 126 patients could not be matched and were thus excluded. Eventually, of the 90 patients with ARDS enrolled in this study, 45 ECMO group patients were matched with 45 non-ECMO group patients. The demographic data, reasons for intensive care unit admission, and laboratory variables were evaluated. Results The primary etiology of ARDS was infection (72.2%). The APACHE II score and age-matched group receiving ECMO therapy had higher inhospital survival rates. Moreover, the patients receiving ECMO therapy had significantly lower 6-month mortality rates than did the non-ECMO group. Conclusions Patients with ARDS who received ECMO treatment had higher inhospital survival rates than did those with a similar disease severity and at a similar age who did not receive ECMO.

Background How hepatitis C virus (HCV)–associated lipid metabolic alterations recover after sustained virological response (SVR) remains elusive. Objective The aforementioned recovery pattern was investigated. Methods In a prospective cohort study of 438 chronic hepatitis C (CHC) patients with SVR after anti-HCV therapy, 164 sex- and age-matched genotype I (G1) and G2 patients underwent paired-serum liquid chromatography-tandem mass spectrometry analyses before and 24 weeks after therapy. Subjects without CHC served as controls (n = 100). Results CHC patients had lower baseline lipid levels than controls. Among CHC patients, pre-therapy total cholesterol levels were positively associated with HCV RNA levels; G1 patients had higher pre-therapy HCV RNA levels than G2 patients. Repeated measures analysis of variance of CHC patients showed that lathosterol, lanosterol, total hydroxysphingomyelin, and total phosphatidylcholines levels, and total dicarboxyacylcarnitine/total acylcarnitine (indicators of ω-oxidation) and pre-β-lipoprotein ratios elevated 24 weeks after therapy compared with the levels before therapy. Levels of total lysophosphatidylcholines and α- and β-lipoprotein ratios decreased. Subgroup analyses showed elevated 7-dehydrocholesterol and lanosterol levels, particularly in G2 and male patients, who had broader spectra of altered phosphatidylcholines and acylcarnitines than G1 and female patients, respectively. Compared with controls, CHC patients had higher post-therapy levels of total lysophosphatidylcholines and hydroxysphingomyelins and ratios of total dicarboxyacylcarnitines/total acylcarnitines but lower cholesterol levels. Conclusions At 24 weeks after therapy, accelerated cholesterol biosynthesis, hepatic lipid export, ω-oxidation, and decreased systemic inflammation were noted in CHC patients with SVR, with greater efficiency in G2 and male patients. Regardless, HCV-associated lipid metabolic alterations required >24 weeks for restoration or were incompletely reversible after SVR.

Background Mortality after coronary artery bypass grafting (CABG) is generally associated with underlying disease and surgical factors overlooked in preoperative prognostic models. Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE II) scores are widely used in intensive care units for outcome prediction. This study investigated the accuracy of these models in predicting mortality. Methods Between January 2010 and April 2013, 483 patients who underwent isolated CABG were enrolled. The clinical characteristics, outcomes, and prognostic model scores of the patients were collected. Discrimination was assessed using the area under the curve approach. Results Both SOFA and APACHE II scores were effective for predicting in-hospital mortality. Among the organ systems examined in the SOFA, the cardiac and renal systems were the strongest predictors of CABG mortality. Multivariate analysis identified only the SOFA score as being an independent risk factor for mortality. Conclusion In summary, the SOFA score can be used to accurately identify mortality after isolated CABG.

Exposure to tobacco smoke has been associated with harmful effects on child health. The association between tobacco smoke exposure and childhood rhinitis has not been established in developed or developing countries. We investigated the association between serum cotinine levels and rhinitis in a population sample of 1,315 Asian children. Serum cotinine levels were positively associated with rhinitis ever (adjusted odds ratio [AOR] = 2.95; 95% confidence interval [CI]: 1.15–7.60) and current rhinitis (AOR = 2.71; 95% CI: 1.07–6.89), while the association for physician-diagnosed rhinitis approaching borderline significance (AOR = 2.26; 95% CI: 0.88–5.83). Stratified analyses demonstrated significant association of serum cotinine levels with current rhinitis among children without allergic sensitization (AOR = 6.76; 95% CI: 1.21–37.74), but not among those with allergic sensitization. Serum cotinine levels were positively associated with rhinitis ever (AOR = 3.34; 95% CI: 1.05–10.61) and current rhinitis (AOR = 4.23; 95% CI: 1.28–13.97) among adolescents but not in children aged less than 10 years. This population-based study demonstrates supportive evidence for positive association of tobacco smoke exposure with rhinitis, while the effect is mainly confined to non-allergic rhinitis and more pronounced in adolescents than in young children, highlighting the need for raising public health awareness about the detrimental effects of tobacco smoke exposure on children’s respiratory health.

IgG Fcγ receptors (FcγRs) mediate a variety of immune functions that are critical in immune responses. In humans, 5 classic low-affinity FcγRs (FcγRIIA, FcγRIIB, FcγRIIC, FcγRIIIA, and FcγRIIIB) are coded by 5 genes (FCGR2A, FCGR2B, FCGR2C, FCGR3A, and FCGR3B, respectively) in the FCGR cluster on chromosome 1. Activating FcγRs (FcγRIIA, FcγRIIC, FcγRIIIA, and FcγRIIIB) mediate immune cell activation promoting inflammation, while the classic inhibitory FcγRIIB dampens immune responses and restricts inflammation (1,2). Activating FcγRs mediate functions including immune complex clearance, phagocytosis, antigen presentation, antibody-dependent cellular cytotoxicity, and cytokine production (3). In contrast, the inhibitory FcγRIIB abrogates immune cell activation. FcγRIIB also plays a role in the maintenance of peripheral B cell tolerance and the prevention of autoimmunity (2). The variations in FcγR expression significantly affect IgG immune complex–mediated signal thresholds (3,4). Notably, proinflammatory and antiinflammatory cytokines could modulate the expression levels of activating and inhibitory FcγRs (5) that affect the threshold immune cell response to IgG immune complexes (6). FcγR-knockout mouse models indicate that both activating and inhibitory FcγRs influence the development of autoimmune diseases (7–9). The contributions of FcγR genes to autoimmune diseases have attracted substantial attention, and functional FcγR polymorphisms have been reported to play important roles in the pathogenesis of autoimmune diseases (4,10,11). Gene copy number variation (CNV) is a rich source of genetic heterogeneity (12,13). The FCGR cluster on chromosome 1q23 shows a complex pattern of CNVs. Among 5 FcγR genes in the cluster, 3 genes (FCGR3A, FCGR2C, and FCGR3B) have CNVs, while FCGR2A and FCGR2B do not have CNVs (14,15). CNVs play important roles in human disease pathogenesis (16). FCGR3B copy number deficiency is associated with autoimmune disease, including systemic lupus erythematosus (SLE) (17–19), Sjogren's syndrome (20), and systemic sclerosis (21). Although FCGR3B CNVs were reported to associate with rheumatoid arthritis (RA) (22–24), no association between RA and FCGR3B CNVs was observed in other studies (25,26). Moreover, no association between FCGR3A CNVs and RA was observed (24,27). In the current study, we investigated whether FCGR3A and FCGR3B CNVs are associated with susceptibility to SLE and RA in Taiwanese individuals. The results provide new insights into the role of FcγRIII family members in the pathogenesis of SLE and RA in an Asian population.

Most cases of oral squamous cell carcinoma (OSCC) develop from visible oral potentially malignant disorders (OPMDs). The latter exhibit heterogeneous subtypes with different transformation potentials, complicating the early detection of OSCC during routine visual oral cancer screenings. To develop clinically applicable biomarkers, we collected saliva samples from 96 healthy controls, 103 low-risk OPMDs, 130 high-risk OPMDs, and 131 OSCC subjects. These individuals were enrolled in Taiwan's Oral Cancer Screening Program. We identified 302 protein biomarkers reported in the literature and/or through in-house studies and prioritized 49 proteins for quantification in the saliva samples using multiple reaction monitoring-MS. Twenty-eight proteins were successfully quantified with high confidence. The quantification data from non-OSCC subjects (healthy controls + low-risk OPMDs) and OSCC subjects in the training set were subjected to classification and regression tree analyses, through which we generated a four-protein panel consisting of MMP1, KNG1, ANXA2, and HSPA5. A risk-score scheme was established, and the panel showed high sensitivity (87.5%) and specificity (80.5%) in the test set to distinguish OSCC samples from non-OSCC samples. The risk score >0.4 detected 84% (42/50) of the stage I OSCCs and a significant portion (42%) of the high-risk OPMDs. Moreover, among 88 high-risk OPMD patients with available follow-up results, 18 developed OSCC within 5 y; of them, 77.8% (14/18) had risk scores >0.4. Our four-protein panel may therefore offer a clinically effective tool for detecting OSCC and monitoring high-risk OPMDs through a readily available biofluid.

Recovery of amino acid (AA) metabolism and the associated clinical implications in chronic hepatitis C (CHC) patients with sustained virological response (SVR) following anti-hepatitis C virus (HCV) therapy remains elusive. A prospective cohort study was conducted on 222 CHC patients with SVR. Eighty-two age-matched male genotype 1 (G1) and G2 patients underwent paired serum metabolomics analyses with liquid chromatography–tandem mass spectrometry to examine AAs before and 24 weeks after anti-HCV therapy. Before anti-HCV therapy, G1 patients had a higher HCV RNA level than G2 patients. Twenty-four weeks post-therapy versus pre-therapy, repeated-measures ANOVA showed that the levels of alanine aminotransferase and most AAs decreased while those of lipids, glutamine and putrescine increased in CHC patients. The methionine sulfoxide/methionine ratio decreased, while the asymmetric dimethylarginine/arginine, glutamine/glutamate, citrulline/arginine, ornithine/arginine, kynurenine/tryptophan, tyrosine/phenylalanine and Fisher’s ratios increased. Genotype-specific subgroup analyses showed that valine and serotonin/tyrosine increased in G1 and that kynurenine and tyrosine/phenylalanine increased and sarcosine decreased in G2 patients. Viral clearance in CHC patients pan-genotypically restored fuel utilization by decelerating the tricarboxylic acid cycle. Following improvement in liver function, the urea, nitric oxide, methionine, and polyamine cycles were accelerated. The cardiometabolic risk attenuated, but the augmented kynurenine pathway activity could increase the oncogenesis risk. The trends in neurotransmitter formation differed between G1 and G2 patients after SVR. Moreover, the HCV-suppressing effect of valine was evident in G1 patients; with the exception of prostate cancer, the oncogenesis risk increased, particularly in G2 patients, at least within 24 weeks post-anti-HCV therapy.

Diagnostic shifts have been prospectively examined in the short term, but the long-term stability of diagnoses has rarely been evaluated. The authors examined diagnostic shifts over a 10-year follow-up period.A cohort of 470 first-admission patients with psychotic disorders was systematically assessed at baseline and at 6-month, 2-year, and 10-year follow-ups. Longitudinal best-estimate consensus diagnoses were formulated after each assessment.At baseline, the diagnostic distribution was 29.6% schizophrenia spectrum disorders, 21.1% bipolar disorder with psychotic features, 17.0% major depression with psychotic features, 2.4% substance-induced psychosis, and 27.9% other psychoses. At year 10, the distribution changed to 49.8%, 24.0%, 11.1%, 7.0%, and 8.1%, respectively. Overall, diagnoses were changed for 50.7% of study participants at some point during the study. Most participants who were initially diagnosed with schizophrenia or bipolar disorder retained the diagnosis at year 10 (89.2% and 77.8%, respectively). However, 32.0% of participants (N=98) originally given a non-schizophrenia diagnosis had gradually shifted to a schizophrenia diagnosis by year 10. The second largest shift was to bipolar disorder (10.7% of those not given this diagnosis at baseline). Changes in the clinical picture explained many diagnostic shifts. In particular, poorer functioning and greater negative and psychotic symptom ratings predicted a subsequent shift to schizophrenia. Better functioning and lower negative and depressive symptom ratings predicted the shift to bipolar disorder.First-admission patients with psychotic disorders run the risk of being misclassified at early stages in the illness course, including more than 2 years after first hospitalization. Diagnosis should be reassessed at all follow-up points.

Objective.To investigate the association of the functional FCRL3 single-nucleotide polymorphism (SNP) −169T/C with disease phenotypes and susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in Taiwanese.Methods.FCRL3 SNP −169T/C was genotyped in 573 patients with SLE, 670 patients with RA, and 758 controls. Genotype distributions and allele frequencies were compared among the 3 groups as aggregates or as stratified by clinical characteristics, autoantibody profile, and sex within patient groups.Results.Overall, FCRL3 SNP −169T/C was not associated with susceptibility to either SLE or RA. However, −169CC genotype was significantly reduced in leukopenia-positive SLE patients as compared to the leukopenia-negative SLE patients (CC vs CT+TT, p = 6 × 10−4, OR 0.444, 95% CI 0.279–0.708) and controls (p = 6.1 × 10−3, OR 0.583, 95% CI 0.396–0.857). On the other hand, −169TT genotypes were significantly more numerous in RA patients with non-destructive disease as compared with patients with destructive disease (CC+CT vs TT: p = 0.007, OR 1.672, 95% CI 1.149–2.432). The −169T allele frequency was also significantly increased in non-destructive RA compared with patients with destructive disease (C vs T: p = 0.010, OR 1.423, 95% CI 1.089–1.859). FCRL3 SNP −169TT homozygous donors were significantly more numerous among female cyclic citrullinated peptide (CCP)-negative RA patients versus female CCP-positive RA patients (CC+CT vs TT: p = 0.019, OR 1.64, 95% CI 1.085–2.479).Conclusion.The functional FCRL3 SNP −169T/C appears to play important roles in the development of certain phenotypes such as SLE leukopenia and RA disease severity in Taiwanese patients with SLE and RA.

Background: Prior studies of common disorders in community-dwelling adults identified internalizing and externalizing spectra of mental illness. We investigated the placement of schizophrenia and schizotypal personality disorder in this framework and tested the validity of the resulting organization in a clinical population. Methods: The data came from the Suffolk County Mental Health Project cohort (N = 628), which consists of first-admission patients with psychosis recruited from inpatient units throughout Suffolk County, NY (72% response rate). The sample was reassessed multiple times over the following 10 years. Complete diagnostic data were available for 469 participants. Mental health professionals diagnosed 11 target conditions based on semistructured clinical interviews, review of medical records, and reports of significant others. Two validators were included: family history of schizophrenia and 10-year illness course. Results: Confirmatory factor analysis revealed that the The Diagnostic and Statistical Manual of Mental Disorders-IV grouping of conditions fit the data poorly. The best alternative classification consisted of three clusters: internalizing, externalizing, and schizophrenic. Both validators supported the coherence and distinctiveness of the schizophrenic cluster. Conclusions: We replicated internalizing and externalizing spectra in a clinical population, identified a schizophrenic spectrum, and provided initial evidence of its validity. These findings suggest that schizotypal personality disorder may be better placed with schizophrenia, antisocial conditions with substance use disorders, and major depression with anxiety disorders.

Background Although there is evidence that exposure to tobacco smoke is harmful to children's respiratory health, the effects of tobacco smoke exposure on the regulation of immunoglobulin E (IgE)-mediated immune responses to specific allergens remain unclear. This study aimed to investigate the relationship between objectively assessed tobacco smoke exposure and specific IgE profiles for a broad spectrum of allergens in a population setting. Methods Children aged 5–18 years (N = 1315) were assessed using serum cotinine measurement and microarray-based multiplexed detection of specific IgE against 40 allergens. Results Serum cotinine levels were positively associated with sensitization to foods (adjusted odds ratio [AOR] = 4.95; 95% CI: 1.59–15.34), cockroaches (AOR = 3.77; 95% CI: 1.49–9.51), and pollen (AOR = 2.84; 95% CI: 1.20–6.73) while the association was borderline significant for animals (AOR = 2.53; 95% CI: 0.92–6.93). No associations were found for sensitization against mites, mold, and latex. When considering the degree of allergic sensitization, serum cotinine levels were positively correlated to the number of sensitization to cockroaches (P = 0.004), pollen (P = 0.006), and foods (P < 0.001), with statistically significant positive dose–response relationships (all P < 0.01). Similar results were observed when summing up specific IgE concentrations for the aforementioned allergen categories. Conclusions The association between tobacco smoke exposure and IgE sensitization to environmental allergens varies for different allergens among children. This study demonstrates that elevated serum cotinine levels are significantly associated with IgE sensitization to cockroaches, grass pollen, and certain foods, with potential dose-dependent relationships.

Background: Acute kidney injury (AKI) after cardiac surgery is associated with short-term and long-term adverse outcomes. Novel biomarkers have been identified for the early detection of AKI; however, examining these in every patient who undergoes cardiac surgery is prohibitively expensive. Society of Thoracic Surgeons (STS) and Age, Creatinine, and Ejection Fraction (ACEF) scores have been proven to predict mortality in bypass surgery. The aim of this study was to determine whether these scores can be used to predict AKI after mitral valve repair. Materials and Methods: Between January 2010 and December 2013, 196 patients who underwent mitral valve repair were enrolled. The clinical characteristics, outcomes, and scores of prognostic models were collected. The primary outcome was postoperative AKI, defined using the Kidney Disease Improving Global Outcome 2012 clinical practice guidelines for AKI. Results: A total of 76 patients (38.7%) developed postoperative AKI. The STS renal failure (AUROC: 0.797, P < .001) and ACEF scores (AUROC: 0.758, P < .001) are both satisfactory tools for predicting all AKI. The STS renal failure score exhibited superior accuracy compared with the ACEF score in predicting AKI stage 2 and 3. The overall accuracy of both scores was similar for all AKI and AKI stage 2 and 3 when the cut-off points of the STS renal failure and ACEF scores were 2.2 and 1.1, respectively. Conclusion: In conclusion, the STS renal failure score can be used to accurately predict stage 2 and 3 AKI after mitral valve repair. The ACEF score is a simple tool with satisfactory power in screening patients at risk of all AKI stages. Additional studies can aim to determine the clinical implications of combining preoperative risk stratification and novel biomarkers.

Background The current literature focusing on the effect of obesity and overweight on lung function and fraction of exhaled nitric oxide (FeNO) in children, particularly among healthy children of non-European descent, remains controversial. Furthermore, whether the relationship of obesity and overweight with lung function and FeNO in children is modified by atopy is unclear. The objective of this study was to examine the effect of excess weight on lung function parameters and FeNO among Asian children, with a particular focus on exploring the potential effect modification by atopy. Methods We investigated the effect of excess weight on lung function and FeNO in a population sample of 1,717 children aged 5 to 18 years and explored the potential modifying effect of atopy. Results There were positive associations of body mass index (BMI) z-score with forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), peak expiratory flow (PEF), and forced expiratory flow at 25–75% (FEF25-75) (all P

Background New evidence shows high prevalence of vitamin D deficiency in many countries and some studies suggest a possible link between vitamin D status and allergic diseases. The objectives of this study were to determine the prevalence of suboptimal vitamin D status in a population sample of Asian children and to investigate the relationship of vitamin D status with allergic diseases and atopy. Methods Children aged 5–18 years (N = 1315) in the Prediction of Allergies in Taiwanese CHildren (PATCH) study were evaluated using questionnaires, anthropometric measurements, and serum levels of 25-hydroxyvitamin D [25(OH)D] and total and specific immunoglobulin E (IgE). Results The mean concentration of serum 25(OH)D was 20.4 ng/mL (SD: 7.1 ng/mL). Vitamin D deficiency (defined as serum 25(OH)D0.05). Conclusions Low serum 25(OH)D levels are remarkably common in this population sample of Asian children, suggesting that millions of children living in Taiwan may have suboptimal levels of vitamin D, which should be a matter of public health concern. Our results provides epidemiological evidence against the association of vitamin D status with various allergic diseases and atopy in Asian children.

This study investigated the relationship between the specific immunoglobulin E (IgE) profile for 40 allergens using a novel microarray technique (BioIC) and fraction of exhaled nitric oxide (FeNO) in a population sample of 1321 children. Significant positive associations were found between FeNO and sensitization to mites (P

Toll-like receptors (TLRs), as innate immunity sensors, play critical roles in immune responses. Six SNPs of TLR3, TLR7, and TLR8 were genotyped to determine their associations with systemic lupus erythematosus (SLE) and clinical manifestations of SLE. TLR7 SNP rs3853839 was independently associated with SLE susceptibility in females (G vs. C: p = 0.0051). TLR7 rs3853839-G (G vs. C: p = 0.0100) and TLR8 rs3764880-G (recessive model: p = 0.0173; additive model: p = 0.0161) were associated with pericardial effusion in females relative to healthy females. Anti-SSA positive cases were more likely to have the dominant TLR7 rs179010-T allele than normal controls (p = 0.0435). TLR3 rs3775296-T was associated with photosensitivity (p = 0.0020) and anemia (p = 0.0082). The "G-G" haplotype of TLR7 rs3853839 and TLR8 rs3764880 increased risk of SLE in females (age adjusted p = 0.0032). These findings suggest that TLR variations that modify gene expression affect risk for SLE susceptibility, clinical phenotype development, and production of autoantibodies.

BACKGROUND: Total serum immunoglobulin (IgE) test is usually performed to aid in the diagnosis of allergic diseases, but its reference values may vary among people of different ethnic backgrounds. OBJECTIVES: To establish reference values of total IgE in Asian children and to assess their significance in the diagnosis of atopy and allergic diseases. STUDY DESIGN: 1321 Asian children aged 5-18 years in the Prediction of Allergies in Taiwanese CHildren (PATCH) study, a population-based cohort, were evaluated for total and specific IgE by ImmunoCAP and Phadiatop Infant, respectively. RESULTS: Male, atopy, allergic diseases, recent symptoms of upper respiratory infection, and lower FEV1/FVC, were associated with higher total IgE levels in univariate analyses. Multivariate analysis revealed that atopy was the single most important determinant explaining 66.1% of the variability of total IgE levels in this population. The area under the receiver-operator characteristic (ROC) curve of total IgE for diagnosing atopy, asthma, rhinitis, and eczema were 0.92, 0.72, 0.70, and 0.70, respectively. The sensitivity, specificity, and positive and negative predictive values of total IgE at the optimal cutoff of 77.7 kU/L on the ROC curve for diagnosing atopy were 82.3%, 87.1%, 89.5%, and 78.6%, respectively. The corresponding values using the upper 95% CI of total IgE (164.3 kU/L) in non-atopic children were 61.2%, 95.0%, 94.3%, and 64.6%, respectively; whereas a customary cutoff (100 kU/L) provided accuracy between that of the aforementioned two cutoffs. Total IgE at the cutoff of 77.7 kU/L provided modest sensitivity and specificity (49.0%-78.3%) for diagnosing allergic diseases, but had high negative predictive values (84.2%-97.9%). CONCLUSIONS: Total serum IgE discriminates Asian children with and without atopy independent of allergic symptoms, with an optimal cutoff of 77.7 kU/L. The study confirms the insufficient diagnostic accuracy of total IgE alone to detect allergic diseases, but low total IgE levels may help exclude allergic diseases.

Objectives Acute kidney injury (AKI) after coronary artery bypass grafting (CABG) is associated with short-term and long-term adverse outcomes. The European System for Cardiac Operative Risk Evaluation (EuroSCORE), EuroSCORE II, the Society of Thoracic Surgeons (STS) score and Age, Creatinine and Ejection Fraction (ACEF) score, have been widely used for predicting the operative risk of cardiac surgery. The aim of this study is to investigate the discriminant ability among current available models in predicting postoperative AKI. Methods From January 2010 to December 2012, 353 patients who underwent isolated CABG were enrolled. The clinical characteristics, outcomes and scores of prognostic models were collected. The primary outcome was postoperative AKI, defined based on the Kidney Disease Improving Global Outcome (KDIGO) Clinical Practice Guideline for AKI, in 2012. Results 102 patients (28.9%) developed postoperative AKI. For AKI prediction, EuroSCORE II, STS score and ACEF score were all good tools for stage-3 AKI. The ACEF score was shown to have satisfied discriminant ability to predict postoperative AKI with area under a receiver operating characteristic curve: 0.781±0.027, (95% CI 0.729 to 0.834, p value

Introduction Ankylosing spondylitis (AS) is a familial, heritable disease specified by syndesmophyte formation leading to an ankylosed spine. Endoplasmic reticulum aminopeptidase 1 (ERAP1) genetic variations have been widely proved to be associated with AS in several ethnic populations. The aim of this study was to investigate whether ERAP1 single nucleotide polymorphisms (SNPs) are associated with AS susceptibility and disease severity in Taiwanese. Methods Four ERAP1 SNPs (rs27037, rs27980, rs27044 and rs30187) were genotyped in 797 Taiwanese AS patients and 1,150 healthy controls. Distributions of genotype and alleles were compared between AS patients and healthy controls, and among AS patients stratified by clinical parameters. Results The SNP rs27037T allele appeared to be a risk factor for AS susceptibility (P = 5.5 × 10-5, OR 1.30, 95% CI: 1.15 to 1.48; GT+TT vs. GG P = 9.3 × 10-5, OR 1.49, 95% CI: 1.22 to 1.82). In addition, the coding SNP (cSNP) rs27044G allele (P = 1.5 × 10-4, OR 1.28, 95% CI: 1.13 to 1.46; CG+GG vs. CC, P = 1.7 × 10-3, OR 1.44, 95% CI: 1.15 to 1.81) and the cSNP rs30187T allele (P = 1.7 × 10-3, OR 1.23, 95% CI: 1.08 to 1.40; CT+TT vs. CC P = 6.1 × 10-3, OR 1.38, 95% CI: 1.10 to 1.74) were predisposing factors for AS. Notably, the rs27044G allele carriers (CG+GG vs. CC, P = 0.015, OR 1.59, 95% CI: 1.33 to 2.30) and rs30187T allele carriers (CT+TT vs. CC, P = 0.011, OR 1.63, 95% CI: 1.12 to 2.38) were susceptible to syndesmophyte formation in AS patients. Furthermore, two cSNPs (rs27044 and rs30187) strongly associated with HLA-B27 positivity in AS patients. Finally, the ERAP1 SNP haplotype TCG (rs27037T/rs27980C/rs27044G) is a major risk factor for AS (adjusted P

Background Single nucleotide polymorphisms (SNPs) of interleukin-28B (IL28B) have received considerable interest for their association with sustained virological response (SVR) when treating patients of genotype-1 hepatitis C virus (GT1-HCV) chronic infection with pegylated interferon and ribavirin (PegIFN/RBV). This study was to investigate the predictive power of IL28B SNPs for on-treatment responses and SVR in treatment-naive patients with GT1-HCV chronic infection. Methodology/Principal Findings We analyzed ten SNPs of IL28B in 191 treatment-naive patients with GT1-HCV chronic infection who received PegIFN/RBV. In these patients, rapid virological response (RVR), early virological response (EVR) and SVR were achieved in 69.6%, 95.8% and 68.6% of the patients, respectively. Multivariate analysis (odds ratio; 95% confidence interval; P value) indicated age (0.96; 0.93–0.99; 0.012), low baseline viral load (4.65; 2.23–9.66

Chronic hepatitis C virus (HCV) infection patients exhibit different sustained virological responses (SVRs) following the treatment with pegylated interferon-α (IFN-α) and ribavirin. Genome-wide association studies consistently linked SVR of IFN-α-based therapy to the IL28B single-nucleotide polymorphisms (SNPs) on chromosome 19q.13 in various populations. This study was undertaken to investigate the association of IL28B SNPs with SVR in a cohort of Taiwanese chronic HCV patients. Ten SNPs of IL28B were genotyped in 728 chronic HCV patients and 960 healthy controls. Genotype distributions, allele frequencies and haplotypes were tested for SVR and susceptibility in Taiwanese chronic HCV patients. Non-genotype 1 infection (adjusted P=3.3 × 10(-12), odds ratio (OR) 0.179; 95% confidence interval (CI): 0.110-0.290) and low HCV viral load (

Supplemental Digital Content is available in the text, Acute kidney injury (AKI) is associated with increased morbidity and mortality and is frequently encountered in coronary care units (CCUs). Its clinical presentation differs considerably from that of prerenal or intrinsic AKI. We used the biomarkers calprotectin and neutrophil gelatinase-associated lipocalin (NGAL) and compared their utility in predicting and differentiating intrinsic AKI. This was a prospective observational study conducted in a CCU of a tertiary care university hospital. Patients who exhibited any comorbidity and a kidney stressor were enrolled. Urinary samples of the enrolled patients collected between September 2012 and August 2013 were tested for calprotectin and NGAL. The definition of AKI was based on Kidney Disease Improving Global Outcomes classification. All prospective demographic, clinical, and laboratory data were evaluated as predictors of AKI. A total of 147 adult patients with a mean age of 67 years were investigated. AKI was diagnosed in 71 (50.3%) patients, whereas intrinsic AKI was diagnosed in 43 (60.5%) of them. Multivariate logistic regression analysis revealed urinary calprotectin and serum albumin as independent risk factors for intrinsic AKI. For predicting intrinsic AKI, both urinary NGAL and calprotectin displayed excellent areas under the receiver operating characteristic curve (AUROC) (0.918 and 0.946, respectively). A combination of these markers revealed an AUROC of 0.946. Our result revealed that calprotectin and NGAL had considerable discriminative powers for predicting intrinsic AKI in CCU patients. Accordingly, careful inspection for medication, choice of therapy, and early intervention in patients exhibiting increased biomarker levels might improve the outcomes of kidney injury.

Cardiocerebral vascular events are the major cause of mortality among patients with end-stage renal disease (ESRD). Subclinical inflammation and atherosclerosis have been implicated in the pathophysiology of ESRD. Evidence has shown the crucial role of interleukin-18 (IL-18) in inflammation. Interleukin-18 has been markedly upregulated in ESRD patients. Nevertheless, the ability of the IL-18 level to predict cardiocerebral vascular events and the correlation between IL-18 levels and cardiocerebral vascular events have not been established in hemodialysis patients. To determine whether the serum IL-18 level predicts cardiocerebral vascular events, the authors studied 171 ESRD patients. Samples were collected and patients were followed for 24 months. Demographic data, the duration of hemodialysis, nutrition status, inflammatory parameters, dialysis adequacy, and lipid profiles were analyzed to predict the outcome by using multivariate logistic regression. Cutoff points were calculated by acquiring the highest Youden index. The Kaplan–Meier method was used to scrutinize the cumulative proportion of events. The multivariate logistic regression model revealed that serum creatinine, C-reactive protein, and IL-18 levels were independent predictors for cardiocerebral vascular events. The odds ratio of events for each increase in IL-18 (pg/mL) was 1.008 for cardiocerebral vascular events. The area under the receiver operating characteristic curve of IL-18 was 0.779 ± 0.039, the overall correctness was 73%, and the Youden index was highest at a cutoff of 463 pg/mL. In the Kaplan–Meier model, patients with an IL-18 level higher than 463 pg/mL exhibited the highest probability of experiencing an adverse event during the entire follow-up period. Increased serum IL-18 could be considered as a predictor of cardiocerebral vascular events in dialysis patients. It is noteworthy that various comorbidities might interfere the expression of IL-18; therefore, further validation study is required to incorporate IL-18 in clinical use.

To investigate the relationship of vitamin D status with lung function and fraction of exhaled nitric oxide (FeNO) in a population sample of children.A total of 1315 children aged 5-18 years were evaluated using serum 25-hydroxyvitamin D [25(OH)D] levels, spirometry, a single-breath online FeNO measurement, and questionnaires.After adjusting for confounders, the mean forced vital capacity was 53.4 mL (SE, 26.5 mL; P = .045), and the mean forced expiratory volume in 1 second was 48.2 mL (SE, 23.6 mL; P = .042) lower for children with insufficient serum 25(OH)D levels (20-29.9 ng/mL) compared with those with sufficient 25(OH)D levels (≥30 ng/mL). The mean difference between children with deficient (20 ng/mL) and sufficient levels of serum 25(OH)D was 81.9 mL (SE, 26.7 mL; P = .002) for forced vital capacity and 55.2 mL (SE, 23.7 mL; P = .020) for forced expiratory volume in 1 second. There was no significant association between serum 25(OH)D levels and FeNO after adjusting for confounders.Our results demonstrate a significant relationship between insufficient serum vitamin D levels and worse lung function in children in the community with a suggested dose-response effect. Our findings also suggest that vitamin D status is not a significant determinant of FeNO in children in the general population.

It is common to observe the clustering of chronic hepatitis B surface antigen (HBsAg) carriers in families. Intra-familial transmission of hepatitis B virus (HBV) could be the reason for the familial clustering of HBsAg carriers. Additionally, genetic and gender factors have been reported to be involved. We conducted a three-stage genome-wide association study to identify genetic factors associated with chronic HBV susceptibility. A total of 1,065 male controls and 1,623 male HBsAg carriers were included. The whole-genome genotyping was done on Illumina HumanHap550 beadchips in 304 healthy controls and HumanHap610 beadchips in 321 cases. We found that rs9277535 (HLA-DPB1, P = 4.87×10(-14)), rs9276370 (HLA-DQA2, P = 1.9×10(-12)), rs7756516 and rs7453920 (HLA-DQB2, P = 1.48×10(-11) and P = 6.66×10(-15) respectively) were significantly associated with persistent HBV infection. A novel SNP rs9366816 near HLA-DPA3 also showed significant association (P = 2.58×10(-10)). The "T-T-G-G-T" haplotype of the five SNPs further signified their association with the disease (P = 1.48×10(-12); OR = 1.49). The "T-T" haplotype composed of rs7756516 and rs9276370 was more prevalent in severe disease subgroups and associated with non-sustained therapeutic response (P = 0.0262). The "G-C" haplotype was associated with sustained therapeutic response (P = 0.0132; OR = 2.49). We confirmed that HLA-DPB1, HLA-DQA2 and HLA-DQB2 loci were associated with persistent HBV infection in male Taiwan Han-Chinese. In addition, the HLA-DQA2 and -DQB2 complex was associated with clinical progression and therapeutic response.