Disparity in survival benefits of pembrolizumab between Asian and non-Asian patients with advanced cancers: A systematic review and meta-regression analysis.

BACKGROUND: Immune checkpoint inhibitors have revolutionized the treatment of malignancies. However, disproportionate enrollment among races and ethnicities places the generalizability of global trial results in doubt. METHODS: In this systematic review, phase 3 randomized controlled trials investigating pembrolizumab in advanced cancers and providing subgroup analyses of Asian and non-Asian participants were included. The primary and secondary effect measures were the mean differences (MDs) in the natural logarithms of the hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) between these two subgroups, respectively. We used random-effects meta-analysis to calculate the pooled ratios of HRs (i.e., exp(MD)) and implemented a meta-regression analysis to identify significant covariates. RESULTS: A total of 17 and 11 trials were included in the meta-analyses of OS and PFS, respectively. These trials included 2732 (25.49%) Asian and 7000 (65.32%) non-Asian participants in the OS analysis and 1438 (22.5%) Asian and 4129 (64.61%) non-Asian participants in the PFS analysis. The pooled ratio of HRs for OS was 0.87 (95% CI: 0.76-0.99; p = 0.0391), favoring Asian participants, but no significant difference was found in PFS (pooled ratio of HRs: 0.93; 95% CI: 0.82-1.07; p = 0.2391). Both linear meta-regression analyses revealed an open-label design as a crucial covariate, which indicated more benefits for non-Asian participants. CONCLUSIONS: Compared with non-Asian patients, Asian patients with advanced cancers may derive superior OS benefits from pembrolizumab. Although the results warrant further exploration, this meta-analysis provides insight into clinical research design.

Quality of life outcomes after surgical intervention in patients with multiple rib fractures: A prospective cohort study.

BACKGROUND: Optimized conservative treatment of rib fractures has long been practiced, but surgical fixation has not been promising until recently. We aimed to examine and analyze immediate postoperative outcomes and 6-month quality of life after injury in patients with moderately severe traumatic rib fractures. METHODS: We conducted a prospective cohort study between July 2017 and June 2019 at the National Taiwan University Hospital. Seventy-two patients with moderately severe thoracic trauma were enrolled; 38 received conservative treatment and 34 underwent surgical fixation. Quality of life was measured using the 36-item Short Form Survey at; the first 3 days of hospitalization; before discharge; and at 1-, 2-, and 6-month follow-ups (visits 1-5). Baseline characteristics and clinical outcomes were recorded, and linear regression analysis was conducted using the generalized estimating equation. RESULTS: Among patients with moderately severe thoracic injury (chest Abbreviated Injury Scale score≥ 2), the operative group had more severe injuries and longer intensive care unit and in-hospital stays. However, they had a comparable quality of life 6 months after injury and higher physical component scores in the early postoperative period. Linear regression analysis obtained an equation with several factors positively affecting prediction of the mean physical component score, such as body mass index ≤25, age ≤36 years, fewer ribs requiring fixation, and diabetes mellitus. Mental component score did not show an upward trend, but the Work Quality Index largely determined the predicted mean value of the mental component score. CONCLUSION: Surgical rib fixations hasten recovery in patients with severe thoracic injury (chest Abbreviated Injury Scale ≥3) to achieve 6-month quality of life comparable to patients injured less severely (chest Abbreviated Injury Scale ≥2). The ability to resume previous work positively influenced the mental component score; thus, surgical intervention should also aim to help patients regain their social function.

Estrogen-DNA Adducts and Breast Cancer Risk in Premenopausal Asian Women.

The incidence of breast cancer among premenopausal women has been increasing rapidly in recent decades in East Asia. This case-control study investigated whether estrogen-DNA adducts were associated with breast cancer risk in Taiwan. The control group (n = 146) comprised healthy female volunteers and women with non-proliferative breast disease. The case group (n = 221) comprised women either with proliferative benign breast disease or breast cancer. The ratios of estrogen-DNA adducts to their respective metabolites and conjugates in plasma were analyzed using ultraperformance LC/MS-MS. The SNPs of CYP1A1, CYP1B1, and COMT were genotyped. Logistic regression model was used to compare the estrogen-DNA adduct ratios between the two groups. The estrogen-DNA adduct ratio in the case group was significantly higher than that in the control group (median ratio: 58.52 vs. 29.36, P = 0.004). A multiple logistic regression model demonstrated that a unit increase in the natural log of the estrogen-DNA adduct ratio in premenopausal women was a significant predictor of breast cancer risk, with an estimated hazard ratio of 1.718 (1.444-2.046, P < 0.001). However, the CYP1A1, CYP1B1, and COMT SNPs were not associated with the estrogen-DNA adduct ratios. In conclusion, plasma estrogen-DNA adduct ratio was associated with the presence of breast cancer or proliferating benign breast disease in premenopausal women in Taiwan. PREVENTION RELEVANCE: This study provides evidence that endogenous estrogen-induced genotoxicity may contribute to the carcinogenesis of breast cancer in premenopausal Asian women. This work could have important preventive implication for the emerging disease in East Asia.

Predictors of Prolonged Euthyroidism After Radioactive Iodine Treatment for Graves' Disease: A Pilot Study.

OBJECTIVE: Patients with Graves' disease who remain hyperthyroid under the treatment of antithyroid drugs (ATD) or cannot tolerate ATD usually receive radioactive iodine (RAI) to control disease activity. This pilot study aimed to identify predictors of prolonged euthyroidism > 12 months after receiving RAI. METHODS: Demographic, clinical, and laboratory data from 117 patients receiving RAI were retrospectively collected, including age, gender, body surface area, smoking status, free thyroxine, thyrotropin, thyrotropin binding inhibiting immunoglobulin, microsomal antibody, thyroglobulin antibody, medication history, and thyroid volume. Only 85 patients without missing values were included in statistical analysis. The calculated RAI dose was the estimated thyroid volume × 0.4. The difference and ratio between the actual and calculated RAI doses were examined. A stepwise logistic regression analysis was conducted to identify important predictors of prolonged euthyroidism > 12 months. The cut-off values for discretizing continuous covariates were estimated by fitting generalized additive models. RESULTS: Among the 85 patients on RAI, 18 (21.2%) achieved prolonged euthyroidism > 12 months, 38 (44.7%) remained hyperthyroid with decreased ATD doses, but 29 (34.1%) suffered permanent hypothyroidism and needed long-term levothyroxine. Logistic regression analysis revealed that patients with age > 66 years, 33 < age ≤ 66 years, quitting smoking vs nonsmoking or current smoking, 600 < micorsomal antibody ≤ 1729 IU/mL, 47% < thyrotropin binding inhibiting immunoglobulin ≤ 81%, 7 < thyroglobulin antibody ≤ 162 IU/mL, 0.63 < ratio between actual and calculated RAI doses ≤ 1.96, or taking hydroxychloroquine would have a higher chance of reaching prolonged euthyroidism > 12 months after receiving RAI. Its area under the Receiver Operating Characteristic (ROC) curve was 0.932. CONCLUSION: Patients with Graves' disease who received an actual RAI dose close to the calculated RAI dose achieved prolonged euthyroidism > 12 months if they also took hydroxychloroquine during RAI treatment.

Lymphocyte count is a universal predictor of health outcomes in COVID-19 patients before mass vaccination: A meta-analytical study.

Background: Several laboratory data have been identified as predictors of disease severity or mortality in COVID-19 patients. However, the relative strength of laboratory data for the prediction of health outcomes in COVID-19 patients has not been fully explored. This meta-analytical study aimed to evaluate the prediction capabilities of laboratory data on the prognosis of COVID-19 patients during 2020 while mass vaccination has not started yet. Methods: Two electronic databases, MEDLINE and EMBASE, from inception to October 10, 2020 were searched. Observational studies of laboratory-confirmed COVID-19 patients with well-defined severity or survival status, and with the desired laboratory data at initial hospital administrations, were selected. Meta-regression analysis with the generalized estimating equations (GEE) method for clustered data was performed sequentially. Primary outcome measures were to compare the level of laboratory data and their impact on different health outcomes (severe vs non-severe, critically severe vs non-critically severe, and dead vs alive). Results: Meta-data of 13 clinical laboratory items at initial hospital presentations were extracted from 76 selected studies with a total of 26 627 COVID-19 patients in 16 countries. After adjusting for the effect of age, 1.03 0.87 (OR = 0.0576; 95% CI = 0.0043-0.4726; P = 0.0079) had a much lower risk of severity, critical severity, and mortality from COVID-19, respectively. Conclusions: Lymphocyte count was the most powerful predictor among the 13 common laboratory variables explored from COVID-19 patients to differentiate disease severity and to predict mortality. Lymphocyte count should be monitored for the prognoses of COVID-19 patients in clinical settings in particular for patients not fully vaccinated.

COQ2 and SNCA polymorphisms interact with environmental factors to modulate the risk of multiple system atrophy and subtype disposition.

BACKGROUND AND PURPOSE: Multiple system atrophy (MSA) has no definitive genetic or environmental (G-E) risk factors, and the integrated effect of these factors on MSA etiology remains unknown. This study was undertaken to investigate the integrated effect of G-E factors associated with MSA and its subtypes, MSA-P and MSA-C. METHODS: A consecutive case-control study was conducted at two medical centers, and the interactions between genotypes of five previously reported susceptible single nucleotide polymorphisms (SNPs; SNCA_rs3857059, SNCA_rs11931074, COQ2_rs148156462, EDN1_rs16872704, MAPT_rs9303521) and graded exposure (never, ever, current) of four environmental factors (smoking, alcohol, drinking well water, pesticide exposure) were analyzed by a stepwise logistic regression model. RESULTS: A total of 207 MSA patients and 136 healthy controls were enrolled. In addition to SNP COQ2_rs148156462 (TT), MSA risk was correlated with G-E interactions, including COQ2_rs148156462 (Tc) × pesticide nonexposure, COQ2_rs148156462 (TT) × current smokers, SNCA_rs11931074 (tt) × alcohol nonusers, and SNCA_rs11931074 (GG) × well water nondrinkers (all p < 0.01), with an area under the receiver operating characteristic curve (AUC) of 0.804 (95% confidence interval [CI] = 0.671-0.847). Modulated risk of MSA-C, with MSA-P as a control, correlated with COQ2_rs148156462 (TT) × alcohol nondrinkers, SNCA_rs11931074 (GG) × well water ever drinkers, SNCA_rs11931074 (Gt) × well water never drinkers, and SNCA_rs3857059 (gg) × pesticide nonexposure (all p < 0.05), with an AUC of 0.749 (95% CI = 0.683-0.815). CONCLUSIONS: Certain COQ2 and SNCA SNPs interact with common environmental factors to modulate MSA etiology and subtype disposition. The mechanisms underlying the observed correlation between G-E interactions and MSA etiopathogenesis warrant further investigation.

Gestational hypertriglyceridemia and adverse pregnancy outcomes: A search for cutoffs using generalized additive models.

OBJECTIVE: To explore cutoffs of gestational hypertriglyceridemia based on the risk of adverse pregnancy outcomes. METHODS: Pregnant women who visited National Taiwan University Hospital for prenatal care were included. Fasting plasma TG in the first and second trimesters were measured. Adverse pregnancy outcomes, including gestational diabetes and large for gestational age, were recorded and used in simple and multiple generalized additive models (GAM) to identify cutoffs for gestational hypertriglyceridemia. RESULTS: We recruited 807 pregnant woman-newborn pairs. Using GAM analyses, we identified plasma TG at 95 or 140 mg/dL (1.07 or 1.58 mmol/L) in the first trimester, and 173 or 220 mg/dl (1.95 or 2.48 mmol/L) in the second trimester as potential cutoffs. Gestational hypertriglyceridemia defined by the higher cutoffs in both trimesters were associated with adverse pregnancy outcomes and had a more reasonable prevalence and better specificity than the lower cutoffs (First trimester plasma TG ≥ 140 mg/dL, adjusted OR 2.56, 95% CI 1.17-5.69, p = 0.019, prevalence 19%, specificity 83%; Second trimester plasma TG ≥ 220 mg/dL, adjusted OR 1.70, 95% CI 1.00-2.87, p = 0.049, prevalence 19%, specificity 81%). CONCLUSIONS: Fasting plasma TG ≥ 140 mg/dL in the first trimester and ≥ 220 mg/dL in the second trimester can be used as cutoffs of gestational hypertriglyceridemia.

Are the measurement structures of the Traditional Chinese Dispositional Flow Scale-2 equivalent between schizophrenic patients and healthy subjects?

BACKGROUND: The Dispositional Flow Scale-2 (DFS-2) is an instrument for measuring the flow experiences of the general population while participating in daily activities. This study aimed to examine the equivalence in the measurement structure of Traditional Chinese DFS-2 (TCDFS-2) between the schizophrenic patients and healthy subjects. METHODS: We recruited 100 adults with schizophrenia or schizoaffective disorder from the psychiatric clinics or the centers for daycare or rehabilitation and 104 healthy adults. Each participant finished the TCDFS-2 by recalling the most important and meaningful daily activity. RESULTS: We conducted two two-group confirmatory factor analyses (CFA) with the healthy subjects and schizophrenic patients as the reference group respectively in LISREL. When the healthy subjects as the reference standard, 43 items of the TCDFS-2 were added to this constrained two-group CFA model for the schizophrenic patients, but the cross-group equivalence was still unsatisfactory. By contrast, when the schizophrenic patients as the reference standard, only 6 items were added for the healthy subjects, and the cross-group equivalence was barely acceptable. CONCLUSION: Thus, the measurement structures of the TCDFS-2 were quite different between the schizophrenic patients and healthy subjects. The flow states experienced by the schizophrenic patients might not entirely be the same as those of the healthy subjects.

Characteristics and outcomes of second cancers in patients with childhood cancer: A report from the Taiwan Pediatric Oncology Group.

BACKGROUND: Patients with childhood cancer are at increased risk for the development of second cancers. METHODS: A national multicenter survey of second cancers conducted by the Taiwan Pediatric Oncology Group retrieved retrospective data from the database at the Children Cancer Foundation in Taiwan beginning in 1995. The characteristics of second cancers and associations of patient demographic and clinical characteristics with time to death due to a second cancer were analyzed. RESULTS: We examined the records of 8782 patients with a primary cancer diagnosed between January 1, 1995 and December 31, 2013, and a total of 99 patients with a second cancer were identified. The most common type of second cancer was acute myeloid leukemia (n = 35), followed by acute lymphoblastic leukemia (n = 15), central nervous system (CNS) tumors (n = 15), and sarcomas (n = 10). Secondary hematological malignancies occurred earlier than other secondary cancers. The frequencies of second CNS tumors and second bone cancers and sarcomas were notably increased when prior radiation doses increased from zero, low dose to high dose. The overall 5-year survival of patients with a second cancer was poor (33.7%). Multivariate survival analysis revealed that the year of primary diagnosis ≤2002, secondary hematological malignancies, and age at second cancer diagnosis ≤9.3 years or >26.8 years increased the risk of death following second cancer. CONCLUSION: Children who develop a second cancer have an unfavorable outcome. Early detection and improved treatment for second cancers are needed.

Factors predicting one or two sentinel lymph nodes to be accepted for sentinel lymph node biopsy alone after neoadjuvant therapy in initially node-positive breast cancer patients.

BACKGROUND: Current guidelines recommend harvesting ≥3 sentinel nodes if sentinel lymph node biopsy (SLNB) alone is considered after neoadjuvant therapy (NAT) for initially node-positive (cN+) breast cancer. We attempted to investigate factors predicting one or two sentinel lymph nodes harvested to be accepted for SLNB alone after NAT in initially cN + patients. METHODS: Overall, 157 patients who received NAT (clinically T1-3/N1-2/M0) and underwent SLNB were identified from a prospectively maintained database. Significant factors were identified using a multiple logistic regression model. RESULTS: The overall SLN identification rate was 83.4%. Failed SLN identification was associated with a 2-day protocol using a single tracer (odds ratio: 0.331 [95% confidence interval {CI}: 0.132-0.830], p = 0.018), age >52 years (0.345 [0.131-0.913], p = 0.032), and lobular histology (0.156 [0.026-0.944], p = 0.043). The overall false-negative SLNB rate was 14.7%. Its increased risk was associated with radioactivity count >530 for any SLN during SLNB (96.4 [4.00-2320], p = 0.005), age ≥57 years (34.2 [1.92-610], p = 0.016), and taxane use (105 [1.02-10700], p = 0.049); its decreased risk was associated with more harvested SLNs (0.191 [0.054-0.669], p = 0.01) and dual tracers (0.101 [0.012-0.843], p = 0.034). A predictive model using these factors achieved an area under the curve of 0.935 (95% CI: 0.878-0.991). CONCLUSION: When taxane was administered during NAT, the false-negative rate was predicted at <5% for patients aged <57 years, if 1-2 SLNs were harvested using dual tracers, and when the count of every SLN was lower than 530 after NAT in cN + breast cancer.

Anti-HER2 antibody prolongs overall survival disproportionally more than progression-free survival in HER2-Positive metastatic breast cancer patients.

BACKGROUND: This meta-analysis aimed to test the hypothesis that the HER2-positive metastatic breast cancer (mBC) patients treated with anti-HER2 antibodies in trial intervention arms have a greater prolongation of overall survival (OS) than of progression-free survival (PFS) and this extra-prolongation of median survival time in OS relates specifically to the anti-HER2 antibody. METHODS: The NCBI/Pubmed and Cochrane databases were searched systematically for HER2-positive or mBC trials published in English during January 1999-November 2017. Treatment arms with shorter PFS were considered as the "control" arm, whereas those with longer PFS as the "test" arm. The between-treatment drug differences were grouped into nine categories. Groups with or without anti-HER2 antibodies were pooled respectively for comparisons. The interrelationships between PFS and OS hazard ratios (HRs) and median survival time differences were investigated by conducting fixed-effects and mixed-effects linear meta-regression analyses. RESULTS: Twenty-eight trials (10,928 patients) from 438 articles were collected, and four with missing data were excluded in meta-regression analysis. Overall median PFS (HR = 0.73, 95% CI: 0.68-0.78) and median OS (HR = 0.82, 95% CI: 0.77-0.87) weakly favored the longer PFS arm with a weak correlation between the PFS and OS HRs. However, the between-treatment drug difference was anti-HER2 antibody, the absolute increment in median OS time was double that of median PFS time (p < 0.001) and linearly correlated, which was not found with any non-anti-HER2 antibody drug differences. CONCLUSIONS: Anti-HER2 antibody in patients with HER2-positive mBC prolonged OS more than PFS and mandates further investigation.

Contrasting Epidemiology and Clinicopathology of Female Breast Cancer in Asians vs the US Population.

BACKGROUND: The incidence of breast cancer among younger East Asian women has been increasing rapidly over recent decades. This international collaborative study systemically compared the differences in age-specific incidences and pathological characteristics of breast cancer in East Asian women and women of predominantly European ancestry. METHODS: We excerpted analytic data from six national cancer registries (979 675 cases) and eight hospitals (18 008 cases) in East Asian countries and/or regions and, for comparisons, from the US Surveillance, Epidemiology, and End Results program database. Linear regression analyses of age-specific incidences of female breast cancer and logistic regression analyses of age-specific pathological characteristics of breast cancer were performed. All statistical tests were two-sided. RESULTS: Unlike female colorectal cancer, the age-specific incidences of breast cancer among East Asian women aged 59 years and younger increased disproportionally over recent decades relative to rates in US contemporaries. For years 2010-2014, the estimated age-specific probability of estrogen receptor positivity increased with age in American patients, whereas that of triple-negative breast cancer (TNBC) declined with age. No similar trends were evident in East Asian patients; their probability of estrogen receptor positivity at age 40-49 years was statistically significantly higher (odd ratio [OR] = 1.50, 95% confidence interval [CI] = 1.36 to 1.67, P < .001) and of TNBC was statistically significantly lower (OR = 0.79, 95% CI = 0.71 to 0.88, P < .001), whereas the probability of ER positivity at age 50-59 years was statistically significantly lower (OR = 0.88, 95% CI = 0.828 to 0.95, P < .001). Subgroup analyses of US Surveillance, Epidemiology, and End Results data showed similarly distinct patterns between East Asian American and white American patients. CONCLUSIONS: Contrasting age-specific incidences and pathological characteristics of breast cancer between East Asian and American women, as well as between East Asian Americans and white Americans, suggests racial differences in the biology.

Traditional-Chinese Dispositional Flow Scale-2 and Flow State Scale-2 in Taiwanese subjects with schizophrenia or schizoaffective disorder.

INTRODUCTION: The 36-item Dispositional Flow Scale-2 (DFS-2) and Flow State Scale-2 (FSS-2) were developed to assess flow experience in daily and specific activities. Although their validity and reliability had been examined in general populations and different cultures, little is known for schizophrenic subjects. Thus, this study aimed to validate Traditional-Chinese DFS-2 (TCDFS-2) and FSS-2 (TCFSS-2) in Taiwanese subjects with schizophrenia or schizoaffective disorder. METHODS: We recruited 229 adult participants from outpatient clinics, day care centers, and psychiatric rehabilitation centers in Taipei. They filled out 36-item TCDFS-2 and TCFSS-2 under guidance. The LISREL 9.30 software was used to conduct exploratory factor analysis for exploring measurement structures, and then confirmatory factor analysis for identifying factor models. RESULTS: The six first-order factor and one second-order factor measurement models were obtained for both 36-item TCDFS-2 (Chi-square statistic = 999.1, df = 545, p < 0.0001, Root Mean Square Error of Approximation [RMSEA] = 0.0603, and Comparative Fit Index [CFI] = 0.9213) and TCFSS-2 (Chi-square statistic = 987.9, df = 539, p < 0.0001, RMSEA = 0.0603, and CFI = 0.9213). CONCLUSION: Our factor models differed remarkably from those of 36-item DFS-2 and FSS-2. Yet, they were barely acceptable to be used to measure flow experiences in schizophrenic subjects in clinical applications. Since the factor scores, measurement structures, or even definitions of flow experiences could differ substantially between healthy people and patients with mental illness, disease-specific instruments of flow experiences should be considered in the future.

Klotho-beta and fibroblast growth factor 19 expression correlates with early recurrence of resectable hepatocellular carcinoma.

BACKGROUND AND AIMS: Fibroblast growth factor 19 (FGF19) and fibroblast growth factor receptor 4 (FGFR4) signalling play critical roles in hepatocarcinogenesis. This study explored the potential of FGF19- and FGFR4-related biomarkers in predicting early tumour recurrence (ETR) and survival in patients with resectable hepatocellular carcinoma (HCC). METHODS: We examined the mRNA expressions of FGF19, FGFR4, klotho-beta (KLB), cyclin D1 (CCND1) and FGF4 in 151 surgically resected, primary unifocal HCCs through quantitative real-time polymerase chain reaction. Generalized additive models were fitted to detect nonlinear effects of continuous covariates and define thresholds of biomarker expressions. Univariate and multivariate analyses were performed to evaluate prognostic values of these biomarkers for tumour recurrence and patient survival. RESULTS: Overexpression of FGF19, FGFR4, KLB, CCND1 and FGF4 mRNA was detected in 40%, 32%, 26%, 15% and 35% of 151 tumours respectively. ETR was the strongest prognostic factor predicting worse overall survival (hazard ratio [HR], 5.678; 95% confidence interval, 3.7-8.713; P < 0.001). Furthermore, we revealed that mRNA expression levels of KLB (HR, 3.857; P = 0.021) and FGF19 (HR, 3.248; P = 0.017) were significantly associated with the occurrence of ETR. CONCLUSIONS: Frequent overexpression of FGF19/FGFR4-related biomarkers was detected in resectable HCC. Expression levels of KLB and FGF19 may determine patient survival outcomes through their effects on ETR.

Diabetes mellitus, superoxide dismutase and peroxisome proliferator activated receptor gamma polymorphisms modify the outcome of end-stage renal disease patients of Han Chinese origin.

AIM: Increased oxidative stress significantly modifies the outcome of patients with diabetes mellitus (DM) and end-stage renal disease (ESRD), and is counteracted by antioxidative capacity. We aimed to investigate whether antioxidant single nucleotide polymorphisms (SNPs) influence the outcome of ESRD individuals and the influences exerted by DM, which has not been tested before. METHODS: We prospectively enrolled multi-centre ESRD patients of Han Chinese origin between 2002 and 2003, recording their antioxidant (superoxide dismutase [SOD2], glutathione peroxidase [GPX1]) and peroxisome proliferator activated receptor-γ (PPAR-γ) genotyping results, and stratified based on DM. They were followed up until 2008, with risk factors for mortality analyzed by Cox proportional hazard regression. RESULTS: We discovered that diabetic ESRD carriers of CC genotype of SOD2 exon 2 had an increased risk of mortality compared to non-diabetic ones with other genotypes (hazard ratio [HR] 4.04, P = 0.04), while GPX1 SNPs had no influence. Interactions between SOD2 and PPAR-γ SNPs regarding the mortality influence were also detected (for SOD2 CC genotype x PPAR-γ exon 6 CT genotype, HR 3.19, P = 0.008), suggesting the importance of considering a combination panel of SNPs on patient survival. CONCLUSION: This might be the largest study focusing on the relationship between antioxidant SNPs and the outcomes of diabetic ESRD patients of Han Chinese origin. More studies are needed to validate our findings.

Predictors of survival in adults undergoing extracorporeal membrane oxygenation with severe infections.

BACKGROUND: To identify novel factors associated with the survival of septic adults receiving extracorporeal membrane oxygenation (ECMO) to improve patient selection and outcomes. METHODS: Cases were identified from our ECMO registry from 2001 to 2011 if they were ≥16 years and received ECMO for life-threatening sepsis. RESULTS: A total of 151 adults with a median (25th-75th percentile) age of 51 (37-63) years were analyzed. Pneumonia (50%), myocarditis (20%), and primary bloodstream infections (15%) were the main types of infection, caused by predominantly nonfermentative Gram-negative bacteria (NFGNB) (26%), Enterobacteriaceae (24%), and Gram-positive cocci (21%). The in-hospital mortality of patients with NFGNB, enteric, and Gram-positive bacterial pneumonias were 100%, 68%, and 14%, respectively. Using the Cox-proportional hazards model, we found that age >75 years (hazard ratio [HR], 1.98, 95% confidence interval [95% CI], 1.30-3.02), pre-ECMO dialysis (HR, 3.20, 95% CI, 1.34-7.63), longer door-to-ECMO intervals (HR, 1.01, 95% CI, 1.00-1.02), venoarterial mode (HR, 2.58, 95% CI, 1.55-4.21), and fungal (HR, 2.83, 95% CI, 1.36-5.88) and NFGNB sepsis (HR, 2.48, 95% CI, 1.44-4.27) were associated with mortality. Gram-positive sepsis (HR, 0.20, 95% CI, 0.08-0.57), myocarditis (HR, 0.12, 95% CI, 0.06-0.27), pneumonia (HR, 0.54, 95% CI, 0.30-0.90), and effective empirical antimicrobial therapy were predictive of survival (HR, 0.57, 95% CI, 0.37-0.89); all P < .05. Excluding the 67 heavily premorbid patients, we found that 54% survived ECMO and 42% survived to discharge, with significantly more survivors with door-to-ECMO times of ≤96 hours than >96 hours (59% vs 15%, P < .0001). CONCLUSIONS: Better outcomes were associated with door-to ECMO times of 96 hours or less, for Gram-positive rather than Gram-negative sepsis, and for pneumonia rather than primary bloodstream infections.

Detecting Visual Function Abnormality with a Contrast-Dependent Visual Test in Patients with Type 2 Diabetes.

In addition to diabetic retinopathy, diabetes also causes early retinal neurodegeneration and other eye problems, which cause various types of visual deficits. This study used a computer-based visual test (Macular Multi-Function Assessment (MMFA)) to assess contrast-dependent macular visual function in patients with type 2 diabetes to collect more visual information than possible with only the visual acuity test. Because the MMFA is a newly developed test, this study first compared the agreement and discriminative ability of the MMFA and the Early Treatment Diabetic Retinopathy Study (ETDRS) contrast acuity charts. Then symbol discrimination performances of diabetic patients and controls were evaluated at 4 contrast levels using the MMFA. Seventy-seven patients and 45 controls participated. The agreement between MMFA and ETDRS scores was examined by fitting three-level linear mixed-effect models to estimate the intraclass correlation coefficients (ICCs). The estimated areas under the receiver operating characteristic (ROC) curve were used to compare the discriminative ability of diseased versus non-diseased participants between the two tests. The MMFA scores of patients and controls were compared with multiple linear regression analysis after adjusting the effects of age, sex, hypertension and cataract. Results showed that the scores of the MMFA and ETDRS tests displayed high levels of agreement and acceptable and similar discriminative ability. The MMFA performance was correlated with the severity of diabetic retinopathy. Most of the MMFA scores differed significantly between the diabetic patients and controls. In the low contrast condition, the MMFA scores were significantly lower for 006Eon-DR patients than for controls. The potential utility of the MMFA as an easy screening tool for contrast-dependent visual function and for detecting early functional visual change in patients with type 2 diabetes is discussed.

Nationwide epidemiology and prognosis of dialysis-requiring acute kidney injury (NEP-AKI-D) study: Design and methods.

AIM: Acute kidney injury (AKI) carries an increasing incidence rate worldwide and increases the risk of developing end-stage renal disease (ESRD) as well as the medical expenses during the post-AKI course. The Taiwan Consortium for Acute Kidney Injury and Renal Diseases (CAKs) has thus launched a nationwide epidemiology and prognosis of dialysis-requiring acute kidney injury (NEP-AKI-D) study, which prospectively enrols critically ill patients with AKI. Through thoroughly evaluating the risk and prognostic factors of AKI, we hope to lower the incidence of AKI and ESRD from the perspective of AKI-ESRD interaction. METHODS: The CAKs includes 30 hospitals which distribute widely through the four geographical regions (north, middle, south, and east) of Taiwan, and have a 1:1 ratio of medical centres to regional hospitals in each region. The NEP-AKI-D study enrols intensive care unit-based AKI patients who receive dialysis in the four seasonal sampled months (October 2014, along with January, April, and July 2015) in the included hospitals. The collected data include demographic information, pertaining laboratory results, dialysis settings and patient outcomes. The data are uploaded in a centre website and will be audited by on-site principal investigators, computer logic gates, and the CAKs staffs. The outcomes of interest are in-hospital mortality, dialysis-dependency and readmission rate within 90 days after discharge. CONCLUSION: The NEP-AKI-D study enrols a large number of representative AKI patients throughout Taiwan. The results of the current study are expected to provide more insight into the risk and prognostic factors of AKI and further attenuated further chronic kidney disease transition.