Distribution and clinical features of lymphomas involving skin in Taiwan.

A wide variety of primary and secondary lymphoma types involves the skin. However, reports with comparisons between both groups are limited in Taiwan. We retrospectively enrolled all cutaneous lymphomas and evaluated their clinicopathologic features. There were 221 cases of lymphoma: 182 (82.3%) primary and 39 (17.7%) secondary. Mycosis fungoides was the most common primary T-cell lymphoma, 92 (41.7%) cases, followed by CD30-positive T-cell lymphoproliferative disorders including lymphomatoid papulosis (n = 33, 14.9%) and cutaneous anaplastic large cell lymphoma (n = 12, 5.4%). The most frequent primary B-cell lymphomas were marginal zone lymphoma (n = 8, 3.6%) and diffuse large B-cell lymphoma (DLBCL), leg type (n = 8, 3.6%). DLBCL including variants was the most common secondary lymphoma involving skin. Most primary lymphomas presented at low-stage (T-cell, 86%; B-cell, 75%), whereas the majority of secondary lymphomas presented at high-stage (T-cell, 94%; B-cell, 100%). Patients with secondary lymphomas had an older mean age, more frequent B symptoms, lower serum albumin and hemoglobin, and a higher frequency of atypical lymphocytes in blood than those with primary lymphomas. In primary lymphomas, older age, lymphoma types, decreased lymphocyte counts and atypical lymphocytes in blood were poorer prognostic factors. In secondary lymphoma patients, lymphoma types, high serum lactate dehydrogenase and low hemoglobin levels predicted poorer survival. We found that the distribution of primary cutaneous lymphomas in Taiwan mirrors that of other Asian countries but shows some differences as compared with Western countries. Primary cutaneous lymphomas have a better prognosis than secondary lymphomas. Histologic classification of lymphomas highly correlated with disease presentation and prognosis.

Association between diminished miRNA expression and the disease status of AML patients: Comparing to healthy control.

BACKGROUND: Changes in ABO blood type caused by a gradual decrease in antigen expression have been found in patients with acute myeloid leukemia (AML). Studies have indicated that alteration of ABO gene methylation accounts for 50% of acquired weak ABO antigen expression in patients with leukemia. However, the molecular mechanisms contributing to the remaining 50% of cases are unknown. We hypothesize that deregulation of miRNA is correlated with weak ABO antigen expression in patients with AML. METHODS: Blood samples of 19 patients with AML and 12 healthy controls were collected, in which the blood type was not changed in these AML patients. Flow cytometric analysis was applied to measure the ABO antigen expression titer among AML patients and controls. A total of 18 leukemia-related miRNAs were analyzed via quantitative real-time polymerase chain reactions. RESULTS: We found that miRNA profiles were correlated with the AML patients, especially in those who had constant or weakened ABO antigen expressions. Compared with healthy controls, the miR-16 and miR-451 expression were significantly lower in either AML cases with weak ABO antigen expressions (p = 0.003, p = 0.028, respectively) or AML cases with constant ABO antigen expressions (p = 0.043, p = 0.040, respectively). Although not statistically significant, decreasing trends in the miR-451 and miR-16 expressions in the AML patients with weakened ABO were observed compared to those with constant ABO antigens. The weak ABO antigen expression might correlate with miRNAs, especially miR-16 and miR-451. CONCLUSION: This study indicated that decreasing in miR-16 and miR-451 was associated with AML and AML with weakened ABO expression. In the future, we will continue to include more cases and exclude the others factor influencing ABO antigen expression, promoter methylation and oxidative stress, to replicate the results of this study and investigate the underlying mechanism of decreasing miR-16 and miR-451 in AML patients with varied ABO antigen expression levels.

Single nucleotide polymorphisms within HLA region are associated with the outcomes of unrelated cord blood transplantation.

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.

The Association Between Single-Nucleotide Polymorphisms of Co-Stimulatory Genes Within Non-HLA Region and the Prognosis of Leukemia Patients With Hematopoietic Stem Cell Transplantation.

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.

Hypoglycemic Effect of Electroacupuncture Combined with Antrodia cinnamomea in Dexamethasone-Induced Insulin-Resistant Rats.

Objective: Antrodia cinnamomea (AC), a medicinal mushroom indigenous to Taiwan, exerts various pharmacologic activities. This study compared and evaluated the hypoglycemic effect of treatment with electroacupuncture (EA) combined with AC in steroid-induced insulin-resistant (SIIR) rats. Materials and Methods: Rats were divided into saline, EA, AC, AC+EA, and rosiglitazone (TZD) groups. Plasma-glucose levels were measured in serial blood samples and compared before and after treatment in each group. The levels of signaling proteins-glucose transporter 4, (GLUT4), phosphoinositide 3-kinase (PI3-K), and 5' adenosine monophosphate-activated protein kinase (AMPK)-were analyzed by Western blotting to explore their mechanisms of action. Results: The AC+EA group had reduced plasma-glucose levels at 30 and 60 minutes in SIIR rats, compared to normal rats, and this was better than the EA, AC, and TZD groups at 60 minutes. Furthermore, the signaling protein (GLUT4, PI3-K, and AMPK) levels were increased significantly. Conclusions: These findings showed improved hypoglycemic activity and insulin resistance after EA combined with AC treatment. Therefore, the combined therapy might be a more-effective method than the individual therapies that elevates the expression of the signal proteins, as observed in this study.

Increasing incidence of prostate cancer in Taiwan: A study of related factors using a nationwide health and welfare database.

Over the past decades, the incidence of prostate cancer in Taiwan kept rising. Many possible factors including the utility of prostate specific antigen tests, lifestyle remodeling, and patient's comorbidities may contribute to the increasing of incidence or prostate cancer. We aim to use the nationwide Health and Welfare Database (HWD) to investigate possible associated factors.We used HWD, a nationwide database of medical information, to assess the incidence of prostate cancer, utilization of prostate-specific antigen (PSA) test, and underlying diseases of patients and to evaluate whether there was a common trend among these factors.In total, 32,508 patients with newly diagnosed prostate cancer from 2006 to 2013 were identified. The incidence rate of prostate cancer per 100,000 men increased from 35.47 in 2006 to 52.87 in 2012. The number of patients with prostate cancer and underlying diseases related to metabolic syndrome increased every year. The number of total PSA tests and patients undergoing PSA testing, as well as average times of PSA testing per person in the whole population, increased every year. The average PSA test times of patients with newly diagnosed prostate cancer within 3 years before the diagnosis of prostate cancer also increased every year. There was a high correlation between the average PSA test times and the number of patients with newly diagnosed prostate cancer (r = 0.9734).The trends of incidence of prostate cancer, utilization of PSA testing, and underlying diseases related to metabolic syndrome at the diagnoses of cancer were similar, increasing every year in the study period. The results suggested that increasing use of PSA tests may increase the diagnosis of prostate cancers. Underlying diseases related to metabolic syndrome might also affect the incidence of prostate cancer.

Association between single nucleotide polymorphisms within HLA region and disease relapse for patients with hematopoietic stem cell transplantation.

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.

Meta-Analysis: Urinary Calprotectin for Discrimination of Intrinsic and Prerenal Acute Kidney Injury.

Background: Urinary calprotectin is a novel biomarker that distinguishes between intrinsic or prerenal acute kidney injury (AKI) in different studies. However, these studies were based on different populations and different AKI criteria. We evaluated the diagnostic accuracy of urinary calprotectin and compared its diagnostic performance in different AKI criteria and study populations. Method: In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched PubMed, Embase, and the Cochrane database up to September 2018. The diagnostic performance of urinary calprotectin (sensitivity, specificity, predictive ratio, and cutoff point) was extracted and evaluated. Result: This study included six studies with a total of 502 patients. The pooled sensitivity and specificity were 0.90 and 0.93, respectively. The pooled positive likelihood ratio (LR) was 15.15, and the negative LR was 0.11. The symmetric summary receiver operating characteristic (symmetric SROC) with pooled diagnostic accuracy was 0.9667. The relative diagnostic odds ratio (RDOC) of the adult to pediatric population and RDOCs of different acute kidney injury criteria showed no significant difference in their diagnostic accuracy. Conclusion: Urinary calprotectin is a good diagnostic tool for the discrimination of intrinsic and prerenal AKI under careful inspection after exclusion of urinary tract infection and urogenital malignancies. Its performance is not affected by different AKI criteria and adult or pediatric populations.

Depression Negatively Impacts Survival of Patients with Metastatic Prostate Cancer.

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.

Preoperative risk assessment improves biomarker detection for predicting acute kidney injury after cardiac surgery.

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.

Single nucleotide polymorphisms within HLA region are associated with disease relapse for patients with unrelated cord blood transplantation.

Disease relapse occurs in unrelated cord blood transplantation (CBT) even when the alleles of human leukocyte antigen (HLA) are fully matched between donor and recipient. This is similar to that observed in other types of hematopoietic stem cell transplantation. Fourteen single nucleotide polymorphisms (SNPs) within the HLA region have been reported previously by Petersdorf et al. and Piras et al. as transplantation determinants in unrelated hematopoietic cell transplantation. In this study, the genomic sequences within 500 base pairs upstream and downstream of the fourteen transplantation-related SNPs from 53 patients and their HLA-matched unrelated donors were analyzed for determining whether or not genetic variants, conferred by either recipient or donor SNP genotype or by recipient-donor SNP mismatching, were associated with the risk of relapse. Seven SNPs were associated with the risk of relapse in unrelated CBT. These included the donor genotype with the SNPs of rs2523675 and rs2518028 at the telomeric end of HCP5 gene, rs2071479 in the intron of the HLA-DOB gene, and rs2523958 in the MICD gene; and the recipient genotype with SNPs of rs9276982 in the HLA-DOA gene, and rs435766 and rs380924 in the MICD gene. As measured by pair-wise linkage disequilibrium (LD) with D' as the parameter for normalized standard measurement of LD which compares the observed and expected frequencies of one haplotype comprised by alleles at different loci, rs2523675 had high LD with rs4713466 (D' = 0.86) and rs2523676 (D' = 0.91) in the HCP5 gene. The rs2518028 had no LD with all other SNPs except rs2523675 (D' = 0.76). This study provides the basis for developing a method or algorithm for selecting better unrelated CBT candidate donors.

Demographic characteristics and complications of open and minimally invasive surgeries for renal cell carcinoma: a population-based case-control study in Taiwan.

INTRODUCTION: Renal cell carcinoma (RCC) is one of the most lethal urological malignancies, and surgeries remain the mainstay for localized RCC. This study aimed to compare the selection of open surgery and minimally invasive kidney surgery for RCCs for the aspects of complication, medical costs, and patient preference. MATERIALS AND METHODS: We conducted a population-based case-control study by using the National Health Insurance Research Database of Taiwan, which included data from 23 million Taiwanese residents. Patients newly diagnosed with RCC during 2006-2012 were included. We compared the general characteristics, underlying disease, complications, hospital stay, postoperative analgesic dosage, and medical costs between open group and minimally invasive group. RESULTS: A total of 3,172 patients who received radical nephrectomy (RN) or partial nephrectomy (PN) for RCC were included. The mean age was 61.1 years, with a male to female ratio of 1.88. In the minimally invasive groups, the mean hospital stay was significantly shorter than in open groups (12.4 days in open RN versus 10.3 days in minimally invasive RN, and 9.7 days in open PN versus 8.2 days in minimally invasive PN). There was no significant difference between the medical costs and the incidence of major bleeding complication between the open group and the minimally invasive group. Female patients and patients with higher monthly income were more likely to receive minimally invasive surgery. CONCLUSION: During past decades, open RN has gradually been replaced by minimally invasive surgeries and PN. Compared to open surgeries, minimally invasive surgeries could lead to less postoperative pain and faster recovery. Economic status of the patients potentially hinders them from receiving minimally invasive surgeries, which may cost more.

Evaluation of the use of the fourth version FloTrac system in cardiac output measurement before and after cardiopulmonary bypass.

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 < 4 L/min was considered inadequate, the Cohen κ coefficient was 0.355 and 0.373 before and after CPB, respectively. The accuracy, trending ability, and inadequate CO-discriminating ability of the fourth version of the FloTrac system in CO monitoring are not statistically acceptable in cardiac surgery.

Sequential organ failure assessment score predicts mortality after coronary artery bypass grafting.

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 and childhood rhinitis: a population-based study.

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.

Recovery of pan-genotypic and genotype-specific amino acid alterations in chronic hepatitis C after viral clearance: transition at the crossroad of metabolism and immunity.

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.

Effect of HLA mismatching at HLA-A, -B, and -DRB1 for umbilical-cord blood transplantation in Taiwan.

Unrelated cord blood transplantation has become a reliable alternative therapy for children and adults owing to that one or two antigen/allele mismatches between a patient and the cord blood donor are acceptable without occurrence of graft-versus-host disease. To investigate the relationship between the number and types of mismatches and relapse, we compared the number of mismatched and non-mismatched donor-recipient pairs, number of mismatched alleles, and number of mismatched antigens at each of the Human Leukocyte Antigen (HLA) -A, -B, and -DR loci, respectively. The result indicates that the number of mismatched antigens at the HLA-A locus was significantly associated with occurrence of relapse (X2P-value=0.0243; RR=1.49, 95% CI: 1.04-2.13). Additionally, the number of mismatched donor-recipient pairs and the number of mismatched alleles at the HLA-DR locus was negatively associated with risks of relapse (X2P-value=0.0028; RR=0.52, 95% CI: 0.31-0.89). In this study, we found that the mismatch at the HLA-A locus is associated with increased risk of relapse; while the mismatch at the HLA-DR locus is innocuous. Hence, we suggest that the well-matched HLA-A alleles were most critical for matching HLA alleles between umbilical-cord blood transplantation donors and recipients. In other words, cord blood transplantation requires less stringent HLA matching, if there are two 5/6 or 4/6 HLA matched donors, it's better to choose HLA-A matched donor at least.

Saliva protein biomarkers to detect oral squamous cell carcinoma in a high-risk population in Taiwan.

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.

Comparison of contemporary preoperative risk models at predicting acute kidney injury after isolated coronary artery bypass grafting: a retrospective cohort study.

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 <0.001). Multivariate logistic analysis identified that lower ejection fraction and higher serum creatinine were independent risk factors for AKI. CONCLUSIONS: The simple and extremely user-friendly ACEF score can accurately identify the risk of postoperative AKI and has shown satisfactory discriminant ability when compared with other systems. The ACEF score might be the easiest tool for predicting postoperative AKI.

Combination of Urinary Biomarkers Improves Early Detection of Acute Kidney Injury in Patients With Heart Failure.

BACKGROUND: Acute kidney injury (AKI) is associated with morality and repeated hospitalization, and is frequently encountered in patients with acute decompensated heart failure (ADHF). However, few effective tools exist for early AKI identification and risk stratification. METHODS AND RESULTS: This was a prospective observational study conducted in the coronary care unit (CCU) of a tertiary care university hospital. Patients with a diagnosis of ADHF and who were using diuretics were enrolled.Samples collected between December 2013 and February 2015 were tested for serum cystatin C (Cys-C), urinary neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 (KIM-1). Demographic, clinical, and laboratory data were evaluated. A total of 103 adult patients with a mean age of 68 years were investigated. AKI was diagnosed in 49 patients (47.6%). For predicting intrinsic AKI on the first day of CCU admission, a combination of Cys-C and urine KIM-1 yielded an excellent area under the receiver operating characteristic curve of 0.828, a sensitivity of 71.0%, and specificity of 43.0%, for an overall accuracy of 78%. CONCLUSIONS: In this study, we found that combinations of the biomarker (Cys-C and KIM-1) were an effective clinical model for predicting AKI in patients with ADHF. The biomarker was also useful for differentiating subclinical AKI in patients with ADHF.