Pancreatic cancer prognosis is predicted by an ATAC-array technology for assessing chromatin accessibility.

Unlike other malignancies, therapeutic options in pancreatic ductal adenocarcinoma (PDAC) are largely limited to cytotoxic chemotherapy without the benefit of molecular markers predicting response. Here we report tumor-cell-intrinsic chromatin accessibility patterns of treatment-naïve surgically resected PDAC tumors that were subsequently treated with (Gem)/Abraxane adjuvant chemotherapy. By ATAC-seq analyses of EpCAM+ PDAC malignant epithelial cells sorted from 54 freshly resected human tumors, we show here the discovery of a signature of 1092 chromatin loci displaying differential accessibility between patients with disease free survival (DFS) < 1 year and patients with DFS > 1 year. Analyzing transcription factor (TF) binding motifs within these loci, we identify two TFs (ZKSCAN1 and HNF1b) displaying differential nuclear localization between patients with short vs. long DFS. We further develop a chromatin accessibility microarray methodology termed "ATAC-array", an easy-to-use platform obviating the time and cost of next generation sequencing. Applying this methodology to the original ATAC-seq libraries as well as independent libraries generated from patient-derived organoids, we validate ATAC-array technology in both the original ATAC-seq cohort as well as in an independent validation cohort. We conclude that PDAC prognosis can be predicted by ATAC-array, which represents a low-cost, clinically feasible technology for assessing chromatin accessibility profiles.

Risk of cancer in patients with ankylosing spondylitis: a nationwide cohort study in Taiwan.

Objective: To estimate the incidence of cancer among patients with ankylosing spondylitis (AS) and compare this risk with that of the general population.Method: We obtained data from Taiwan's National Health Insurance database on 19 289 patients with a first diagnosis of AS registered between 2000 and 2012 with no history of cancer before the diagnosis of AS. Standardized incidence ratios (SIRs) for all cancers and for site-specific cancers were used to assess whether AS was associated with an increased risk of cancer.Results: During the follow-up period, 485 patients developed cancer. The incidence rate was therefore 256.3 per 100 000 person-years. Compared with the general population, patients with AS had an increased risk of cancer [SIR 1.33, 95% confidence interval (CI) 1.20-1.47]. The SIR of cancer was higher in older patients; the risk increased from 8 years after initial diagnosis. Among solid tumours, the risk of melanoma was the highest (SIR 4.64, 95% CI 1.93-11.15), followed by prostate (SIR 2.53, 95% CI 2.01-3.19), thyroid (SIR 2.09, 95% CI 1.45-3.00), and bone cancer (SIR 2.00, 95% CI 1.01-3.99). Among haematological cancers, the risk of leukaemia was the highest (SIR 1.94, 95% CI 1.21-3.12). By contrast, the risks of oesophageal and oral cancers decreased in patients with AS.Conclusion: This nationwide population-based cohort study demonstrated that patients with AS in Taiwan are at an increased risk of cancer, particularly melanoma; prostate, thyroid, and bone cancers; and haematological malignancies.

Oral Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat (FG-4592) for Treatment of Anemia in Chronic Kidney Disease: A Placebo-Controlled Study of Pharmacokinetic and Pharmacodynamic Profiles in Hemodialysis Patients.

Roxadustat (FG-4592), an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that stimulates erythropoiesis, was evaluated in a phase 1b study in patients with end-stage renal disease with anemia on hemodialysis. Seventeen patients, on epoetin-alfa maintenance therapy with stable hemoglobin levels ≥10 g/dL, had epoetin-alfa discontinued on day 3 and were enrolled in this double-blind placebo-controlled study. Two cohorts were randomized 3:1 (roxadustat: placebo). Patients received single doses of roxadustat (1 or 2 mg/kg) or placebo 1 hour after hemodialysis on day 1 and 2 hours before dialysis on day 8. Maximum plasma concentration and area under the plasma concentration-time curve for patients receiving roxadustat were slightly more than dose proportional and elimination half-life ranged from 14.7 to 19.4 hours. Roxadustat was highly protein bound (99%) in plasma, and dialysis contributed a small fraction of the total clearance: only 4.56% and 3.04% of roxadustat recovered from the 1 and 2 mg/kg dose groups, respectively. Roxadustat induced transient elevations of endogenous erythropoietin that peaked between 7 and 14 hours after dosing and returned to baseline by 48 hours after dosing. Peak median endogenous erythropoietin levels were 96 mIU/mL and 268 mIU/mL for the 1- and 2-mg/kg doses, respectively, within physiologic range of endogenous erythropoietin responses to hypoxia at high altitude or after blood loss. No serious adverse events were reported, and there were no treatment- or dose-related trends in adverse event incidence.

The phenotypical implications of immune dysregulation in fragile X syndrome.

BACKGROUND AND PURPOSE: Immune system dysfunction and inflammatory dysregulation have been shown in several animal models of fragile X syndrome (FXS). However, the phenotypical implications of this dysregulation have not been systematically evaluated in a large patient cohort. METHODS: Five thousand seven hundred thirty-six FXS patients from a nationwide health insurance database were identified and compared to 573 600 age- and sex-matched controls. The phenome-wide association studies codes of FXS patients and those without FXS were compared and the false discovery rate was controlled at 0.05 using the Benjamini-Hochberg procedure. RESULTS: In addition to the commonly reported comorbidities of FXS, an over-representation of infectious diseases, including otitis media, cellulitis and abscess of fingers or toes, viral enteritis, candidiasis and pneumonia, was discovered. In addition, there was an under-representation of autoimmune disorders in FXS patients. CONCLUSIONS: Our systematic comorbidity analyses identified immunologically-based phenotypes associated with FXS. Our findings align with previous observations of compromised immunity and phagocytic defects in animal models of FXS. These results suggest the importance of immune-related pathways in FXS patients and their relevance to the FMR1 gene.

Association between time to treatment and functional outcomes according to the Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score in endovascular stroke therapy.

BACKGROUND AND PURPOSE: The rate at which the chance of a good outcome of endovascular stroke therapy (EVT) decays with time when eligible patients are selected by baseline diffusion-weighted magnetic resonance imaging (DWI-MRI) and whether ischaemic core size affects this rate remain to be investigated. METHODS: This study analyses a prospective multicentre registry of stroke patients treated with EVT based on pretreatment DWI-MRI that was categorized into three groups: small [Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS)] (8-10), moderate (5-7) and large (<5) cores. The main outcome was a good outcome at 90 days (modified Rankin Scale 0-2). The interaction between onset-to-groin puncture time (OTP) and DWI-ASPECTS categories regarding functional outcomes was investigated. RESULTS: Ultimately, 985 patients (age 69 ± 11 years; male 55%) were analysed. Potential interaction effects between the DWI-ASPECTS categories and OTP on a good outcome at 90 days were observed (Pinteraction  = 0.06). Every 60-min delay in OTP was associated with a 16% reduced likelihood of a good outcome at 90 days amongst patients with large cores, although no associations were observed amongst patients with small to moderate cores. Interestingly, the adjusted rates of a good outcome at 90 days steeply declined between 65 and 213 min of OTP and then remained smooth throughout 24 h of OTP (Pnonlinearity  = 0.15). CONCLUSIONS: Our study showed that the probability of a good outcome after EVT nonlinearly decreased, with a steeper decline at earlier OTP than at later OTP. Discrepant effects of OTP on functional outcomes by baseline DWI-ASPECTS categories were observed. Thus, different strategies for EVT based on time and ischaemic core size are warranted.

Deep Transfer Learning and Radiomics Feature Prediction of Survival of Patients with High-Grade Gliomas.

BACKGROUND AND PURPOSE: Patient survival in high-grade glioma remains poor, despite the recent developments in cancer treatment. As new chemo-, targeted molecular, and immune therapies emerge and show promising results in clinical trials, image-based methods for early prediction of treatment response are needed. Deep learning models that incorporate radiomics features promise to extract information from brain MR imaging that correlates with response and prognosis. We report initial production of a combined deep learning and radiomics model to predict overall survival in a clinically heterogeneous cohort of patients with high-grade gliomas. MATERIALS AND METHODS: Fifty patients with high-grade gliomas from our hospital and 128 patients with high-grade glioma from The Cancer Genome Atlas were included. For each patient, we calculated 348 hand-crafted radiomics features and 8192 deep features generated by a pretrained convolutional neural network. We then applied feature selection and Elastic Net-Cox modeling to differentiate patients into long- and short-term survivors. RESULTS: In the 50 patients with high-grade gliomas from our institution, the combined feature analysis framework classified the patients into long- and short-term survivor groups with a log-rank test P value < .001. In the 128 patients from The Cancer Genome Atlas, the framework classified patients into long- and short-term survivors with a log-rank test P value of .014. For the mixed cohort of 50 patients from our institution and 58 patients from The Cancer Genome Atlas, it yielded a log-rank test P value of .035. CONCLUSIONS: A deep learning model combining deep and radiomics features can dichotomize patients with high-grade gliomas into long- and short-term survivors.

MiR-93 blocks STAT3 to alleviate hepatic injury after ischemia-reperfusion.

OBJECTIVE: Signal transducer and activator of transcription 3 (STAT3) is correlated with ischemia-reperfusion (I-R) injury. The previous studies showed a decreased miR-93 expression after I-R injury of heart or brain organs, but without knowledge in liver tissues. This study aims to investigate effects of MiR-93 on the hepatic injury after ischemia/reperfusion. MATERIALS AND METHODS: Rat liver I-R model was generated. Liver function indexes including alanine transaminase (ALT) and aspartate aminotransferase (AST) were quantified, and serum tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) levels were quantified. Hepatic tissue apoptosis was measured by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL), and expression of microRNA-93 (miR-93), STAT3, and phosphorylated STAT3 (p-STAT3) were measured. Dual luciferase reporter gene assay confirmed targeted relationship between miR-93 and STAT3. Agomir or miR-93 agomir was injected into the peritoneal cavity of I-R model, followed by ALT and AST assays. Serum levels of TNF-α, IL-1ß, and IL-6 were measured, followed by TUNEL assay for comparing STAT3 and p-STAT3 expression. RESULTS: Comparing to sham group, I-R group rat showed significantly elevated serum ALT, AST, TNF-α, IL-1ß, and IL-6 contents, along with significantly elevated hepatic cell apoptosis, plus decreased miR-93 expression, whilst STAT3 and p-STAT3 expression was enhanced. Intraperitoneal injection of miR-93 agomir significantly decreased STAT3 or p-STAT3 expression, and decreased cell apoptotic rate. Serum levels of ALT, AST, TNF-α, IL-1ß, and IL-6 were significantly decreased, accompanied by improved liver function. CONCLUSIONS: Hepatic I-R injury is accompanied by miR-93 down-regulation, plus STAT3 up-regulation. Overexpression of miR-93 significantly depressed STAT3 expression in liver I-R injury, alleviated hepatic injury or apoptosis, decreased inflammatory response, and improved liver function.

Roxadustat (FG-4592) Versus Epoetin Alfa for Anemia in Patients Receiving Maintenance Hemodialysis: A Phase 2, Randomized, 6- to 19-Week, Open-Label, Active-Comparator, Dose-Ranging, Safety and Exploratory Efficacy Study.

BACKGROUND: Roxadustat (FG-4592) is an oral hypoxia-inducible factor prolyl-hydroxylase inhibitor that promotes erythropoiesis through increasing endogenous erythropoietin, improving iron regulation, and reducing hepcidin. STUDY DESIGN: Phase 2, randomized (3:1), open-label, active-comparator, safety and efficacy study. SETTING & PARTICIPANTS: Patients with stable end-stage renal disease treated with hemodialysis who previously had hemoglobin (Hb) levels maintained with epoetin alfa. INTERVENTION: Part 1: 6-week dose-ranging study in 54 individuals of thrice-weekly oral roxadustat doses versus continuation of intravenous epoetin alfa. Part 2: 19-week treatment in 90 individuals in 6 cohorts with various starting doses and adjustment rules (1.0-2.0mg/kg or tiered weight based) in individuals with a range of epoetin alfa responsiveness. Intravenous iron was prohibited. OUTCOMES: Primary end point was Hb level response, defined as end-of-treatment Hb level change (ΔHb) of -0.5g/dL or greater from baseline (part 1) and as mean Hb level ≥ 11.0g/dL during the last 4 treatment weeks (part 2). MEASUREMENTS: Hepcidin, iron parameters, cholesterol, and plasma erythropoietin (the latter in a subset). RESULTS: Baseline epoetin alfa doses were 138.3±51.3 (SD) and 136.3±47.7U/kg/wk in part 1 and 152.8±80.6 and 173.4±83.7U/kg/wk in part 2, in individuals randomly assigned to roxadustat and epoetin alfa, respectively. Hb level responder rates in part 1 were 79% in pooled roxadustat 1.5 to 2.0mg/kg compared to 33% in the epoetin alfa control arm (P=0.03). Hepcidin level reduction was greater at roxadustat 2.0mg/kg versus epoetin alfa (P<0.05). In part 2, the average roxadustat dose requirement for Hb level maintenance was ∼1.7mg/kg. The least-squares-mean ΔHb in roxadustat-treated individuals was comparable to that in epoetin alfa-treated individuals (about -0.5g/dL) and the least-squares-mean difference in ΔHb between both treatment arms was -0.03 (95% CI, -0.39 to 0.33) g/dL (mixed effect model-repeated measure). Roxadustat significantly reduced mean total cholesterol levels, not observed with epoetin alfa. No safety concerns were raised. LIMITATIONS: Short treatment duration and small sample size. CONCLUSIONS: In this phase 2 study of anemia therapy in patients with end-stage renal disease on maintenance hemodialysis therapy, roxadustat was well tolerated and effectively maintained Hb levels.

Safety and efficacy of oral febuxostat for treatment of HLA-B*5801-negative gout: a randomized, open-label, multicentre, allopurinol-controlled study.

OBJECTIVES: This phase IIIB study compared the efficacy and safety of febuxostat and allopurinol in gout patients with or without tophi who were HLA-B*5801 negative. METHOD: Eligible patients were randomized to a febuxostat group (80 mg QD) or an allopurinol group (300 mg QD). Following an initial 2-week washout period, over the next 12 weeks we made five measurements of serum urate levels along with assessments of adverse events (AEs). RESULTS: Forty-three out of 152 screened subjects (28.3%) were ineligible either because of the presence of the HLA-B*5801 allele or for various other reasons. The febuxostat group (n = 54) and the allopurinol group (n = 55) had no significant differences in demographic or baseline characteristics. From week 2 to week 12, the febuxostat group had a significantly lower serum urate level than the allopurinol group (p ≤ 0.001 for all comparisons) and significantly more patients with serum urate levels less than 6.0 mg/dL. The serum urate levels of the febuxostat group declined by more than 40% from week 2 to week 12 and this decrease was greater than that in the allopurinol group (~30%). The two groups were similar in terms of AEs. CONCLUSIONS: Febuxostat was more effective than allopurinol in reducing the serum urate levels of Han Chinese patients with gout or tophaceous gout who were HLA-B*5801 negative, without causing any serious skin reactions. Febuxostat should be considered for treatment of Han Chinese patients with gout who are HLA-B*5801 negative.

COL1A1 gene -1997G/T polymorphism and risk of osteoporosis in postmenopausal women: a meta-analysis.

Studies investigating the association between the COL1A1 gene -1997G/T polymorphism and the risk of osteoporosis in postmenopausal women have reported conflicting results. We performed a meta-analysis based on the evidence currently available from the literature to make a more precise estimation of this relationship. We conducted searches of the published literature in the PubMed and Embase databases up to September 2014. We estimated the pooled odds ratios with their 95% confidence intervals to assess the associations using fixed- or random-effect models. Publication bias was investigated by Begg's funnel plot. Meta-analysis was performed using the STATA package version 12.0. No significant association was found between the -1997G/T polymorphism in the COL1A1 gene and osteoporosis risk in the total population analysis (TT vs GG: OR = 1.28, 95%CI = 0.76-2.17; TT vs GT: OR = 1.04, 95%CI = 0.60-1.78; dominant model: OR = 0.84, 95%CI = 0.50-1.40; recessive model: OR = 1.18, 95%CI = 0.84- 1.66). In a subgroup analysis by nationality, the results also showed that no significant associations between the COL1A1 gene -1997G/T polymorphism and osteoporosis risk existed in either Caucasian or Asian populations. No evidence of publication bias was found. In conclusion, the COL1A1 gene -1997G/T polymorphism might not be a risk factor for osteoporosis in postmenopausal women. Further large and well-designed studies are needed to confirm these conclusions.

Role of hydrogen sulfide within the dorsal motor nucleus of the vagus in the control of gastric function in rats.

BACKGROUND: Hydrogen sulfide (H2 S) is a gaseous messenger and serves as an important neuromodulator in the central nervous system. This study aimed to clarify the role of H2 S within the dorsal motor nucleus of the vagus (DMV) in the control of gastric function in rats. METHODS: Cystathionine ß-synthetase (CBS) is an important generator of endogenous H2 S in the brain. We investigated the distribution of CBS in the DMV using immunohistochemical method, and the effects of H2 S on gastric motility and on gastric acid secretion. KEY RESULTS: CBS-immunoreactive (IR) neurons were detected in the rostral, intermediate and caudal DMV, with the highest number of CBS-IR neurons in the caudal DMV, and the lowest in the intermediate DMV. We also found that microinjection of the exogenous H2 S donor NaHS (0.04 and 0.08 mol/L; 0.1 µL; n = 6; p < 0.05) into the DMV significantly inhibited gastric motility with a dose-dependent trend, and promoted gastric acid secretion in Wistar rats. Microinjection of the same volume of physiological saline (PS; 0.1 µL, n = 6, p > 0.05) at the same location did not noticeably change gastric motility and acid secretion. CONCLUSIONS & INFERENCES: The data from these experiments suggest that the CBS that produces H2 S is present in the DMV, and microinjection of NaHS into the DMV inhibited gastric motility and enhanced gastric acid secretion in rats.

A phase II, open-label, multicenter study to evaluate the antitumor efficacy of CO-1.01 as second-line therapy for gemcitabine-refractory patients with stage IV pancreatic adenocarcinoma and negative tumor hENT1 expression.

BACKGROUND: Nucleotide transporters such as human equilibrative nucleoside transporter-1 (hENT1) play a major role in transporting gemcitabine into cells. CO-1.01 (gemcitabine-5'-elaidate) is a novel cytotoxic agent consisting of a fatty acid derivative of gemcitabine, which is transported intracellularly independent of hENT1. CO-1.01 was postulated to have efficacy as a second-line treatment in gemcitabine-refractory pancreatic adenocarcinoma in patients with negative tumor hENT1 expression. METHODS: Eligibility criteria included patients with either a newly procured or archival biopsy tumor confirming the absence of hENT1 and either gemcitabine-refractory metastatic pancreas adenocarcinoma or with progression of disease following resection during or within 3 months of adjuvant gemcitabine therapy. Patients were treated with intravenous infusion of CO-1.01 dosed at 1250 mg/m(2) on Days 1, 8, and 15 of a 4-week cycle. The primary end point was disease control rate (DCR). RESULTS: Nineteen patients were enrolled of which 18 patients were evaluable for efficacy assessment. Thirteen patients (68%) had liver metastases, 6 (32%) had lymph node metastases, and 10 (53%) had lung metastases. Two of 18 patients (11%) achieved disease control. The median survival time was 4.3 (95% CI 2.1-8.1) months. All patients experienced at least one treatment-related adverse event with the majority of events being mild or moderate. CONCLUSION: This study did not meet its primary endpoint and no efficacy signal was identified for CO-1.01 in treating progressive metastatic pancreas adenocarcinoma.

A phase II study of gemcitabine and cisplatin plus sorafenib in patients with advanced biliary adenocarcinomas.

BACKGROUND: This study evaluated the addition of sorafenib to gemcitabine and cisplatin in biliary adenocarcinoma first-line therapy. METHODS: Patients with advanced biliary adenocarcinomas received gemcitabine 1000 mg m(-2) and cisplatin 25 mg m(-2) on a 2 weeks on/1 week off cycle and sorafenib 400 mg twice daily. After the initial 16 patients were enrolled, the chemotherapy doses were amended in view of grade 3 and 4 hand-foot skin reaction and haematologic toxicity. Subsequently, 21 patients received gemcitabine 800 mg m(-2), cisplatin 20 mg m(-2) and sorafenib 400 mg. The primary end point was an improvement in 6-month progression-free survival (PFS6) from historical 57-77% (90% power, type I error of 10%). Pretreatment pERK, evaluated by immunostaining, was correlated with clinical outcome. RESULTS: A total of 39 patients were accrued. The most common grade 3-4 toxicities noted in >10% of patients were fatigue, elevated liver function tests and haematologic toxicities including thromboemboli, hyponatraemia and hypophosphataemia. Six-month progression-free survival was 51% (95% confidence interval (CI) 34-66%). Median PFS and overall survival were 6.5 (95% CI: 3.5-8.3) and 14.4 months (95% CI: 11.6-19.2 months), respectively. No correlation was observed between pERK and outcomes. CONCLUSION: The addition of sorafenib to gemcitabine and cisplatin in biliary adenocarcinomas did not improve efficacy over historical data, and toxicity was increased.

The association between low-dose aspirin use and the incidence of colorectal cancer: a nationwide cohort study.

BACKGROUND: Considerable evidence suggests that aspirin has a chemopreventive effect on colorectal cancer (CRC). However, optimal dose and treatment duration have not been defined, and data on the effects of low-dose aspirin are contradictory. AIM: To determine if the incidence of CRC in patients with low-dose aspirin use was lower than in those without aspirin use. METHOD: From Taiwan's National Health Insurance research database, aspirin users (n = 1985) were defined as adults (age ≥20 years) with at least 3.5 years of regular low-dose aspirin use (50-150 mg per day) between 1998 and 2002. Non-users (n = 7940) were those who did not use aspirin and were matched 4:1 with the user group by age, gender, date of ambulatory care (index date), and presence of known risk factors for cardiovascular disease (including hypertension, diabetes mellitus and hyperlipidaemia). Follow-up of the two study groups was made until the end of 2010, and incidences and hazard ratios of colorectal cancer were determined. RESULTS: During a median follow-up period of 8.9 years, 129 non-users and 14 users developed CRC, corresponding to incidence rates of 180.43 and 79.42 per 100,000 person-years respectively. Duration of aspirin use among users ranged from 3.5 to 12.6 years (mean 8.7 years). The multivariate-adjusted hazard ratio for CRC was 0.5 (95% confidence interval 0.28-0.87) among users as compared with non-users. CONCLUSIONS: Long-term use of low-dose aspirin appears to be associated with a lower incidence of CRC in patients with high cardiovascular risk. Further randomised clinical trials are necessary to confirm these findings.

Voices from a minority: experiences of chinese male nursing students in clinical practice.

In Hong Kong, males constituted only about 10.2% of the nursing workforce in 2010. The learning experiences of male nursing students in Hong Kong during their clinical practicum have rarely been explored. If these students cannot maintain their psychological well-being and psychological health in formal education and clinical placements, then their physical health will also suffer. This ethnographic qualitative study gave male nursing students in Hong Kong a chance to voice their experiences during their clinical practicum. Selected through snowball sampling, 18 male nursing students from a local university participated in individual face-to-face semistructured interviews. The data were processed with content analysis. The findings indicated that male students not only received more support and understanding from male rather than female members of staff but endured a certain amount of oppression while working in female wards. According to the students' comments on nursing culture, the work climate of male nursing students could be improved by reorganizing the clinical placements and providing extra support to male nursing students.

T2-weighted MR imaging early after chemoradiotherapy to evaluate treatment response in head and neck squamous cell carcinoma.

BACKGROUND AND PURPOSE: T2-weighted MRI shows potential in early posttreatment assessment of the primary tumor. Residual masses composed entirely of low T2-signal scar tissue suggest local control and those ≥1 cm of similar signal to untreated tumor suggest local failure. The purpose of this study was to investigate the diagnostic accuracy of T2-weighted MR imaging early after chemoradiotherapy for identifying primary tumor treatment failure in squamous cell carcinoma of the head and neck. MATERIALS AND METHODS: At 6 weeks after treatment, T2-weighted MR images of 37 primary tumors in 37 patients were assessed. Residual masses were divided into 3 patterns: pattern 1 = scar tissue only (flat-edged/retracted mass of low T2 signal intensity); pattern 2 = mass without features described in pattern 1 or 3; and pattern 3 = any pattern that included an expansile mass ≥1 cm of intermediate T2 signal intensity (similar grade of signal intensity to the untreated tumor). T2 patterns were analyzed for local outcome (Fisher exact test) and time to local failure (univariate and multivariate analysis of T2 pattern, age, T stage, and tumor size by use of the Cox regression model). RESULTS: Residual masses after treatment were present in 34 (92%) of 37 patients. Local failures occurred in residual masses with pattern 1 in 0 (0%) of 14 patients; pattern 2 in 6 (55%) of 11 patients; and pattern 3 in 9 (100%) of 9 patients. Significant associations were found between local control and pattern 1 (P = <.0001; sensitivity, 74%; specificity, 100%; PPV, 100%; NPV, 75%; accuracy, 85%), and between local failure and pattern 3 (P = <.0001; sensitivity, 60%; specificity, 100%; PPV, 100%; NPV, 76%; accuracy, 82%). Pattern 2 showed no significant associations with local outcome. Univariate analysis of time to local failure showed that the T2 pattern was significant (P < .0001) and remained significant on multivariate analysis. CONCLUSIONS: T2-weighted MR imaging is a potential tool for early posttreatment assessment of primary HNSCC treatment response. Awareness of correlation of the T2 pattern of any residual mass with treatment outcome at the primary site may contribute to patient treatment.

Cytomegalovirus infection causes morbidity and mortality in patients with autoimmune diseases, particularly systemic lupus: in a Chinese population in Taiwan.

To investigate the clinical outcome of cytomegalovirus (CMV) infection in febrile hospitalized patients with autoimmune diseases, mostly systemic lupus erythematosus (SLE). Fifty-four febrile patients were analyzed retrospectively. Half were diagnosed as CMV infection, by positive CMV pp65 antigenemia assay. Clinical and laboratory data between two groups were compared. Correlation between laboratory data and SELENA-SLEDAI scores/mortality were analyzed in the CMV infection group. Receiver operating characteristic analysis was performed to determine the cutoff points of different parameters for predicting mortality or morbidity. The CMV infection group received a higher corticosteroid dosage (mean 26.3 mg/day) and a higher percentage of azathioprine use before admission than the non-CMV infection group. In the former, the deceased subgroup had a significantly higher number of infected leukocytes for CMV (shortened as CMV counts, P = 0.013), more cases of bacterial infection (P = 0.090), and a higher SLE disease activity index score (P = 0.072) than the alive subgroup. The CMV infection group had lower lymphocyte count and more positive bacterial infection than the non-CMV infection group did (P = 0.013 and P = 0.027, respectively). A level of 25 CMV particles/5 × 10(5) polymorphonuclear neutrophils (PMN) was the best cutoff point for predicting CMV-associated mortality, with a sensitivity of 75.0% and specificity of 72.2%. Moderate dose (30 mg/day) of prednisolone or azathioprine use predisposes patients with autoimmune diseases to CMV infection with concurrent bacterial infection. In particular, peak CMV counts at 25/5 × 10(5) PMN or low lymphocyte counts predict mortality or morbidity, respectively.

Cancer risk among patients with systemic sclerosis: a nationwide population study in Taiwan.

OBJECTIVES: Systemic sclerosis (SSc) has been associated with high cancer risk. We compared the cancer risk among SSc patients with that among the general Taiwanese population. METHODS: The catastrophic illness registry of the Taiwan National Health Insurance Research Dataset (NHIRD) was used to identify patients diagnosed with SSc and cancer in Taiwan during 1996-2008. The standardized incidence ratio (SIR) for cancer was calculated, and mortality was ascertained using the data from the National Death Registry. RESULTS: Data analysis revealed that 2053 (472 men, 1581 women) Taiwanese individuals were diagnosed with SSc during the study period and 83 (30 men, 53 women) had cancer. The incidence of cancer was 6.9/1000 person-years. The most common cancer sites in male SSc patients were the lung (n = 10), oral cavity and pharynx (n = 8), and gastrointestinal tract (n = 4), and those in female patients were the breast (n = 11), lungs (n = 11), and blood (n = 6). Compared to the Taiwanese population of 1996, the all-cancer SIR for SSc was 1.63 [95% confidence interval (CI) 1.31-2.01]. Cancer risk was elevated for cancers of the lung (SIR 4.20), oral cavity and pharynx (SIR 3.67), and blood (SIR 3.50). A cancer diagnosis in SSc patients was associated with a hazard ratio (HR) of 2.15 (95% CI 1.30-3.53). Among cancer patients, a diagnosis of SSc was not associated with increased mortality. CONCLUSIONS: SSc patients are at high risk of developing cancer, especially of the lung, oral cavity and pharynx, and blood.

Antinuclear antibody status and risk of death in children and adolescents.

OBJECTIVES: The association between the presence of antinuclear antibodies (ANA) and mortality has been rarely reported. The present study explored the value of ANA as a predictor of overall survival in children and adolescents. METHODS: Patients younger than 20 years who underwent ANA testing in Chang Gung Memorial Hospital (CGMH) from 2000 to 2008 were enrolled in this study. Mortality was ascertained by using the National Death Registry of Taiwan. Positive ANA titres were categorized as low (1:40 to 1:80), medium (1:160 to 1:320), and high (≥ 1:640). RESULTS: A total of 13 345 subjects (6579 males, 6766 females) were enrolled during the 9-year study period. The overall prevalence of low, medium, and high ANA titres was 20.8% (n = 2774), 6.0% (n = 804), and 2.5% (n = 338), respectively. During 45,140 person-years of follow-up, 146 deaths were identified and the crude mortality rates were 3.8 and 3.0 per 1000 person-years for subjects with positive and negative ANA test results, respectively (p = 0.130). Compared with ANA-negative subjects, the adjusted hazard ratio (HR) for all-cause mortality among those with a high ANA titre was 5.18 [95% confidence interval (CI) 3.13-8.57]. A low-to-medium ANA titre was not associated with increased mortality. Among the 18 deaths in individuals with a high ANA titre, 14 were due to systemic lupus erythematosus (SLE). In comparison, five out of 34 deaths among those with low-to-medium titres of ANA and none of those with negative ANA were related to SLE. CONCLUSIONS: Children and adolescents with high ANA titres should receive greater attention and monitoring to prevent unfavourable outcomes because they have a higher mortality risk than those with negative ANA results.

Incidence, cancer risk and mortality of dermatomyositis and polymyositis in Taiwan: a nationwide population study.

BACKGROUND: Nationwide data on the epidemiology of dermatomyositis (DM) and polymyositis (PM) were limited. OBJECTIVES: This study was to estimate the incidence, occurrence of cancer and mortality of DM and PM in Taiwan. METHODS: Both the register of critical illness of the Taiwan National Health Insurance Research Dataset and the National Death Registry of Taiwan were used to calculate estimates of the incidence, cancer association, and mortality of DM and PM between 2003 and 2007. RESULTS: A total of 803 DM and 500 PM cases were identified between 2003 and 2007. Mean age at diagnosis was 44·0 ± 18·3 years for DM and 49·2 ± 15·9 years for PM. The overall annual incidences of DM and PM were 7·1 (95% CI 6·6-7·6) and 4·4 (95% CI 4·0-4·8) cases per million population. The incidence of both DM and PM increased with age and reached a peak at age 50-59 years. One hundred and eleven (13·8%) patients with DM and 31 (6·2%) patients with PM had cancers. The diagnosis of most cancers was made after the diagnoses of DM (n = 71; 64·0%) and PM (n = 21; 67·7%). Overall, the standardized incidence ratios (SIR) for cancer were 5·36 (4·12-6·87) and 1·80 (1·10-2·79) among patients with DM and PM; however, during the first year, SIRs for cancer were 24·55 (95% CI 18·62-31·79) and 9·17 (95% CI 14·82-15·93) in patients with DM and PM, respectively. The most common types of cancer were nasopharyngeal cancer for men and breast cancer for women. Patients with DM and PM had standardized mortality ratios of 7·68 (6·41-9·01) and 5·29 (4·28-6·48). CONCLUSION: This study reports robust estimates of important aspects of the epidemiology of both DM and PM in Taiwan. This highlights the rarity of these diseases, and their associated cancer risks and increased mortality.