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.

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.

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.

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.

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.

Changing risk awareness and personal protection measures for low to high pathogenic avian influenza in live-poultry markets in Taiwan, 2007 to 2012.

BACKGROUND: Outbreaks of low and high pathogenic avian influenza (LPAI, HPAI) H5N2 in chickens have occurred in Taiwan since 2003 and 2012, respectively. Fully understanding the different awareness, attitudes and protective behaviors adopted by workers in live-poultry markets (LPMWs) and local community residents (CRs) to face the challenges of LPAI and HPAI is very important to minimize viral adaptations to human populations. METHODS: A structural questionnaire containing information on respondents' occupation, personal risk awareness, attitudes toward different policies, and preventative measures was administered. The two-stage survey (before and after HPAI H5N2 outbreaks) was conducted from 2007 to 2012, including: (1) 430 LPMWs and 418 CRs at LPMs from different geographical areas of Taiwan after the government announced outbreaks of LPAI H5N2 during 2007-2009, and (2) 73 LPMWs and 152 CRs at two LPMs in central Taiwan after the HPAI H5N2 outbreaks in 2012. The chi-squared test and logistic regression were applied for univariate and multivariate analyses, respectively. RESULTS: Before HPAI-H5N2 outbreaks, higher educated respondents demonstrated greater risk awareness and concerns regarding AI. However, LPM-workers protected themselves less from AI viruses (AIVs) and had lower acceptance of human or avian influenza vaccines. Most importantly, the participants who opposed (versus agreed with) the policy on banning live-poultry slaughtering at LPMs reported lower awareness of government prevention and control policies [Odds Ratio (OR): 0.76, 95 % Confidence Interval (CI): 0.56-1.01] or practiced preventive measures (OR: 0.42, 95 % CI: 0.25-0.70). After HPAI-H5N2 outbreaks, the risk awareness about AI in central Taiwan significantly increased [LPAI to HPAI LPMWs: 34.6 to 65.6 %, p < 0.05; CRs: 44.0 to 76.5 %, p < 0.05] and LPMWs' belief in the effectiveness of vaccination to prevent human or avian influenza virus infection strikingly decreased (92.3 to 68.5 %, p < 0.05). CONCLUSIONS: Risk awareness depends on high or low pathogenicity of AIVs, working in LPMs, levels of education, age, and proximity to the sites of severe AI outbreaks. Regardless of novel LPAI or HPAI virus reassortants that pose public health risks, prompt and clear risk communication focusing on both correct information about AIVs and the most appropriate preventive measures are important for effective prevention of human infection.

Chlorhexidine for the prevention of bloodstream infection associated with totally implantable venous ports in patients with solid cancers.

PURPOSE: To evaluate the preventive effects of topical skin disinfection with chlorhexidine on bloodstream infection (BSI) associated with totally implantable venous port (Port-A). METHODS: Two consecutive cohorts of solid cancer patients were prospectively followed for the occurrence of Port-A associated BSI (PABSI). The first cohort used povidone-iodine as topical skin disinfection and the second cohort used chlorhexidine. The primary endpoint was the time to first PABSI. Propensity score analysis was applied. The preventive effects of chlorhexidine were analyzed by Cox proportional hazards models. RESULTS: There were 396 patients (81,752 catheter-days) in the iodine cohort and 497 (99,977 catheter-days) in the chlorhexidine cohort. Gram-negative bacteria were the most common pathogens to cause first episode of PABSI (iodine cohort (I) vs chlorhexidine cohort (C) and 0.404 vs 0.450 per 1,000 catheter-day), followed by Gram-positive bacteria (I vs C and 0.269 vs 0.110 per 1,000 catheter-day), and fungi (I vs C and 0.098 vs 0.070 per 1,000 catheter-day). Three hundred forty-three patients were selected from each cohort by propensity score match analysis. Chlorhexidine use was associated with a significant improvement on time to first PABSI caused by Gram-positive bacteria (log-rank test, p=0.00175; HR=0.35, 95 % CI, 0.14-0.85, p=0.02). No significant preventive effects of chlorhexidine on time to first PABSI caused by Gram-negative bacteria or fungi was found. CONCLUSIONS: Chlorhexidine topical skin disinfection may prevent PABSI caused by Gram-positive bacteria in patients with solid cancers. The nonsignificant effect on preventing overall PABSI may be attributed to the high incidence of Gram-negative bacteria related PABSI.

Effects of maternal screening and universal immunization to prevent mother-to-infant transmission of HBV.

BACKGROUND & AIMS: Mother-to-infant transmission is the major cause of hepatitis B virus (HBV) infection among immunized children. There has been much debate about screening pregnant women and administering hepatitis B immunoglobulin (HBIG) to newborns. We analyzed the rate of HBV infection among children born to hepatitis B surface antigen (HBsAg)-positive mothers and whether HBIG administration reduces transmission. METHODS: We analyzed data from 2356 children born to HBsAg-positive mothers, identified through prenatal maternal screens. In addition to HBV vaccines, HBIG was given to all 583 children with hepatitis B e antigen (HBeAg)-positive mothers and to 723 of 1773 children with HBeAg-negative mothers. Serology tests for HBV were performed from 2007 to 2009, when children were 0.5-10 years old. RESULTS: A significantly greater percentage of children with HBeAg-positive mothers tested positive for antibodies against the hepatitis B core protein (16.76%) and HBsAg (9.26%) than children with HBeAg-negative mothers (1.58% and 0.29%, respectively; P < .0001 and <.001). Among the HBV-infected children, the rate of chronicity also was higher among children with HBeAg-positive mothers than children with HBeAg-negative mothers (54% vs 17%; P = .002). Similar rates of antibodies against the hepatitis B core protein (0.99% and 1.88%; P = .19) and HBsAg (0.14% and 0.29%; P = .65) were noted in children born to HBeAg-negative mothers who were or were not given HBIG. Infantile fulminant hepatitis developed in 1 of 1050 children who did not receive HBIG (.095%). CONCLUSIONS: Children born to HBeAg-positive mothers are at greatest risk for chronic HBV infection (9.26%), despite immunization. Administration of HBIG to infants born to HBeAg-negative mothers did not appear to reduce the rate of chronic HBV infection, but might prevent infantile fulminant hepatitis. Screening pregnant women for HBsAg and HBeAg might control mother-to-infant transmission of HBV.

Frequent EGFR mutations in nonsmall cell lung cancer presenting with miliary intrapulmonary carcinomatosis.

Nonsmall cell lung cancer (NSCLC) presenting with miliary intrapulmonary carcinomatosis (MIPC) is rare. We investigated the clinical characteristics and epidermal growth factor receptor (EGFR) mutation rate of NSCLC patients with MIPC at initial diagnosis. From June 2004 to December 2008, we screened newly diagnosed NSCLC patients for MIPC using image-based criteria. We recorded clinical data and analysed EGFR mutation status. For comparison, we collected specimens from stage IV NSCLC patients without MIPC tested for EGFR mutations from April 2001 to November 2008. From 3,612 NSCLC patients, 85 patients with MIPC at initial diagnosis were identified; 81 had adenocarcinoma. Of the 85 patients, 60 had specimen sequencing to detect EGFR mutation; 42 (70%) were positive. Compared with 673 stage IV patients without MIPC, patients with MIPC had higher EGFR mutation rate (p=0.036); even male smokers had a high EGFR mutation rate (91%). Multivariate analysis of prognostic factors for overall survival of the 85 patients with MIPC revealed that adenocarcinoma, absence of extrapulmonary metastasis and having EGFR mutation were associated with longer overall survival. NSCLC patients with MIPC at initial diagnosis had higher rates of adenocarcinoma and EGFR mutation. EGFR tyrosine kinase inhibition may be the treatment of choice for NSCLC patients with MIPC at initial diagnosis among Asians.

Risks perception of electromagnetic fields in Taiwan: the influence of psychopathology and the degree of sensitivity to electromagnetic fields.

Little is known about the perceived health risks of electromagnetic fields (EMFs) and factors associated with risk perception in non-Western countries. Psychological conditions and risk perception have been postulated as factors that facilitate the attribution of health complaints to environmental factors. This study investigated people's perceived risks of EMFs and other environmental sources, as well as the relationships between risk perception, psychopathology, and the degree of self-reported sensitivity to EMFs. A total of 1,251 adults selected from a nationwide telephone interviewing system database responded to a telephone survey about the relationships between environmental sources and human health. The interview included questions assessing participants' psychiatric conditions and the presence and degree of sensitivity to EMFs. One hundred and seventy participants were self-identified as having sensitivity to EMFs, and 141 met the criteria for psychiatric conditions without EMF sensitivity. More than half of the survey respondents considered power lines and mobile phone base stations to affect people's health to a big extent. Higher sensitivity to EMFs, psychopathology, being female, being married, more years of education, and having a catastrophic illness had positive associations with perceived risks of EMF-related environmental sources as well as for all environmental sources combined. We observed no moderating effect of psychopathology on the association between degree of sensitivity to EMF and risk perception. Thus, psychopathology had influence on general people's risk perception without having influence on the relationship between people's degree of sensitivity to EMF and risk perception. The plausible explanations are discussed in the text.

Estimating quality weights for EQ-5D (EuroQol-5 dimensions) health states with the time trade-off method in Taiwan.

BACKGROUND/PURPOSE: EQ-5D (EuroQol-5 dimensions) is a preference-based measure of health, which is widely used in cost-utility analyses. It has been suggested that each country should develop its own value set. We therefore sought to develop the quality weights of the EQ-5D health states with the time trade-off (TTO) method in Taiwan. METHODS: A total of 745 respondents consisting of employees and volunteers in 17 different hospitals were recruited and interviewed. Each of them valued 13 of 73 EQ-5D health states using the TTO method. Based on the three exclusion criteria for valuation data, only 456 (61.21%) respondents were considered eligible for data analysis. The quality weights for all EQ-5D health states were modeled by generalized estimating equations (GEEs). RESULTS: Over half of the responses were given negative values, and the medical personnel seemed to have a significantly higher TTO value (+0.1) than others after controlling for other predictors. The N3 model (level 3 occurred within at least 1 dimension) yielded an acceptable fit for the observed OTT data [mean absolute error (MAE) = 0.056, R(2) = 0.35]. The magnitude of mean absolute differences (MADs) between Taiwan data and those from the UK, Japan, and South Korea ranged from 0.146 to 0.592, but the rank correlation coefficients were all above 0.811. CONCLUSION: This study reaffirms the differences in health-related preference values across countries. The high proportion of negative values might indicate that we have also partially measured the intensity of fear in addition to the utility of different health states.

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.

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.

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.

Factors impacting prognosis prediction in BCLC stage C and Child-Pugh class A hepatocellular carcinoma patients in prospective clinical trials of systemic therapy.

BACKGROUND: The purpose of this study was to determine the prognostic significance of clinical factors and staging systems for survival of hepatocellular carcinoma (HCC) patients who are candidates for therapeutic clinical trials. METHODS: From December 1990 to July 2005, 236 patients with unresectable HCC were enrolled into six published phase II trials assessing various therapeutic regimens. Of these, 156 chemotherapy-naive patients with Child-Pugh class A and Barcelona Clinic Liver Cancer stage C disease were included in this analysis. Twenty-seven relevant clinical characteristics were analyzed to identify prognostic factors of survival. Beyond these prognosticators, the predictive ability of eight staging systems (the tumor-node-metastasis, Okuda, Cancer of the Liver Italian Program [CLIP], Chinese University Prognostic Index, Japanese Integrated Staging, Tokyo, National Taiwan University Risk Estimation, and Advanced Liver Cancer Prognostic System [ALCPS] score) were compared using the Akaike information criteria. RESULTS: The median overall survival time was 129 days (95% confidence interval, 111-147 days). Significant predictors of a shorter overall survival time were an Eastern Cooperative Oncology Group performance status score ≥2, the presence of symptoms, ascites, an aspartate transaminase level more than two times the upper limit of normal, and regional lymph node involvement. The ALCPS and CLIP scores were superior to the other systems for predicting survival. CONCLUSIONS: The prognosis of patients with advanced HCC who are candidates for therapeutic clinical trials is affected by several factors related to the patient, liver function, and the tumor. The ALCPS and CLIP scores appear to be superior to the other systems for predicting survival.

Secular trend of the viral genotype distribution in children with chronic hepatitis B virus infection after universal infant immunization.

UNLABELLED: Genotypes B and C are the major hepatitis B virus (HBV) genotypes in Taiwan, and genotype C is associated with more severe liver disease than genotype B. Whether the implementation of the hepatitis B immunization program has affected the secular trend of the HBV genotype distribution remains unknown. We thus investigated the HBV genotypes in hepatitis B surface antigen (HBsAg)-carrier children born before the implementation of the universal infant immunization program and in those born afterward. One hundred seven children who were infected with HBV despite appropriate immunization were enrolled as immunized cases with HBV breakthrough infection. Each case was matched with two unimmunized HBsAg carriers according to the age at enrollment. HBV genotypes were determined with molecular methods. Compared with unimmunized HBsAg carriers, more immunized children had HBsAg-positive mothers (65.9% versus 100%, P < 0.001) and were infected with genotype C (16.4% versus 42.1%, P < 0.001). Among the children born to HBsAg-positive mothers, the mothers' and children's HBV genotypes were highly concordant in both unimmunized [κ = 0.97, 95% confidence interval (CI) = 0.90-1.00] and immunized children (κ = 0.97, 95% CI = 0.92-1.00). After adjustments for gender, maternal age, and delivery mode, immunized HBsAg-carrier children born to HBsAg-positive mothers had a higher likelihood of genotype C infection than unimmunized children (odds ratio = 3.03, 95% CI = 1.62-5.65, P = 0.001). However, the increased genotype C to genotype B ratio was not seen in the HBsAg-carrier mother pool in the postimmunization era. CONCLUSION: In the postimmunization era, most HBV breakthrough infections are due to maternal transmission, and immunized children born to genotype C mothers may have a higher rate of breakthrough infection than those born to genotype B mothers.

A critical evaluation of the preventive effect of antiviral therapy on the development of hepatocellular carcinoma in patients with chronic hepatitis C or B: a novel approach by using meta-regression.

BACKGROUND: The extent of the effect of antiviral therapy and its predictors in preventing hepatocellular carcinoma (HCC) development in patients with chronic hepatitis C (CHC) or B (CHB) remain unclear. METHODS: We conducted a systemic review and meta-analysis of published randomized controlled trials (RCTs) and cohort studies (CSs) up to December 2010. Preventive efficacy was measured as absolute reduction in 3- and 5-year cumulative incidence of HCC with antiviral therapy. Predictors for efficacy were identified by using meta-regression. RESULTS: Twenty-two studies (5 RCTs; 17 CSs) were included for analysis. Antiviral therapy reduced 5-year cumulative incidence of HCC by 7.8% (95% CI 4.6-11.1; p < 0.0001) in patients with CHC and by 7.1% (95% CI 4.1-10.2; p < 0.0001) in patients with CHB. The efficacy was significant as early as 3 years after antiviral therapy. While adjusting for available study-level, patient and virological factors, RCT and higher sustained virological response were identified as pertinent predictors of superior preventive efficacy in patients with CHC, whereas lower hepatitis B virus e antigen seropositivity was identified in patients with CHB. Antiviral therapy did not result in differential preventive efficacy between cirrhotic and noncirrhotic patients with CHC or CHB. CONCLUSION: Antiviral therapy can reduce 3- and 5-year cumulative incidence of HCC in patients with CHC or CHB.

Dynamic contrast-enhanced MRI in advanced nonsmall-cell lung cancer patients treated with first-line bevacizumab, gemcitabine, and cisplatin.

PURPOSE: To investigate dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) of advanced nonsmall-cell lung cancer (NSCLC) patients treated with the antiangiogenic agent bevacizumab combined with gemcitabine and cisplatin as first-line treatment. MATERIALS AND METHODS: All patients were enrolled for MRI and computed tomography (CT) before and after the first three courses of bevacizumab combination chemotherapy. Pharmacokinetic parameters (K(trans), k(ep), v(e), v(p)) derived from DCE MRI were computed for the main mass. Parametric histogram analysis was obtained to evaluate changes of the internal tumor composition and for correlation with tumor response measured on CT. RESULTS: After three cycles of treatment, 11 patients showed decreased tumor size and a decreased value of all MR-derived pharmacokinetic parameters. Among these parameters, there was a significant decrease of mean and standard deviation of the K(trans) histogram as well as a decrease of mean of the k(ep) histogram (P < 0.05). Tumors with larger mean values of rate constant k(ep) (P < 0.0001) and smaller standard deviation of volume of extravascular extracellular space fraction v(e) (P < 0.0001) on histograms before chemotherapy were considered predictors for treatment response. CONCLUSION: DCE MRI enables a functional analysis of the treatment response of NSCLC. MRI parametric histogram has the potential to predict early treatment response of combined bevacizumab, gemcitabine, and cisplatin.