A number of patient-specific and leukemia-associated factors are related to the poor outcome in older patients with acute myeloid leukemia (AML). However, comprehensive studies regarding the impact ...of genetic alterations in this group of patients are limited. In this study, we compared relevant mutations in 21 genes between AML patients aged 60 years or older and those younger and exposed their prognostic implications. Compared with the younger patients, the elderly had significantly higher incidences of PTPN11, NPM1, RUNX1, ASXL1, TET2, DNMT3A and TP53 mutations but a lower frequency of WT1 mutations. The older patients more frequently harbored one or more adverse genetic alterations. Multivariate analysis showed that DNMT3A and TP53 mutations were independent poor prognostic factors among the elderly, while NPM1 mutation in the absence of FLT3/ITD was an independent favorable prognostic factor. Furthermore, the status of mutations could well stratify older patients with intermediate-risk cytogenetics into three risk groups. In conclusion, older AML patients showed distinct genetic alterations from the younger group. Integration of cytogenetics and molecular mutations can better risk-stratify older AML patients. Development of novel therapies is needed to improve the outcome of older patients with poor prognosis under current treatment modalities.
BACKGROUND: Selenium is an essential trace element with antioxidant property. Decreased serum selenium concentration with aging had been found in previous report. In this study, we aim to investigate ...the association between serum selenium and the inflammatory cytokine interleukin-6 in the elderly living in long-term care facilities in Taiwan. MATERIALS AND METHODS: A total of 336 subjects aged 65 years and older (range of age: 65–101 years) were recruited from eight long-term care facilities in 2002–2003. Baseline characteristics, anthropometric indices, and biochemical data were obtained. Selenium deficiency was defined as serum selenium concentration < 80 μg/L. Multiple logistic and linear regression analyses were used to examine the relationships between selenium deficiency and interleukin-6 (divided into quartiles). RESULTS: The prevalence of selenium deficiency was 35.6% in men and 43.2% in women, respectively. After adjusting for potential confounders using multiple logistic regression analysis, interleukin-6 quartiles were significantly associated with selenium deficiency. Compared to the interleukin-6 quartile I, the adjusted odds ratios of having selenium deficiency for interleukin-6 quartile II, III, IV were 1.00(0.50∼2.01), 1.24 (0.62∼2.50), and 2.35(1.15‖4.83), respectively. The increasing odds ratios for selenium deficiency in higher interleukin-6 quartiles revealed dose-response effects (p < 0.05). Moreover, multiple linear regression analysis showed that serum selenium was significantly inversely associated with interleukin-6 after adjusting for potential confounders. CONCLUSIONS: Serum selenium was inversely associated with inflammatory cytokine interleukin-6 among elderly living in long-term care facilities in Taiwan. Monitoring serum selenium should be considered in these institutionalized elderly.
Recent developments in the instrumentation and data analysis of synchrotron small‐angle X‐ray scattering (SAXS) on biomolecules in solution have made biological SAXS (BioSAXS) a mature and popular ...tool in structural biology. This article reports on an advanced endstation developed at beamline 13A of the 3.0 GeV Taiwan Photon Source for biological small‐ and wide‐angle X‐ray scattering (SAXS–WAXS or SWAXS). The endstation features an in‐vacuum SWAXS detection system comprising two mobile area detectors (Eiger X 9M/1M) and an online size‐exclusion chromatography system incorporating several optical probes including a UV–Vis absorption spectrometer and refractometer. The instrumentation and automation allow simultaneous SAXS–WAXS data collection and data reduction for high‐throughput biomolecular conformation and composition determinations. The performance of the endstation is illustrated with the SWAXS data collected for several model proteins in solution, covering a scattering vector magnitude q across three orders of magnitude. The crystal‐model fittings to the data in the q range ∼0.005–2.0 Å−1 indicate high similarity of the solution structures of the proteins to their crystalline forms, except for some subtle hydration‐dependent local details. These results open up new horizons of SWAXS in studying correlated local and global structures of biomolecules in solution.
A new endstation for biological small‐ and wide‐angle X‐ray scattering is detailed, which provides development opportunities for studying correlated local and global structures of biomolecules in solution.
The optical design and performance of the recently opened 13A biological small‐angle X‐ray scattering (SAXS) beamline at the 3.0 GeV Taiwan Photon Source of the National Synchrotron Radiation ...Research Center are reported. The beamline is designed for studies of biological structures and kinetics in a wide range of length and time scales, from angstrom to micrometre and from microsecond to minutes. A 4 m IU24 undulator of the beamline provides high‐flux X‐rays in the energy range 4.0–23.0 keV. MoB4C double‐multilayer and Si(111) double‐crystal monochromators (DMM/DCM) are combined on the same rotating platform for a smooth rotation transition from a high‐flux beam of ∼4 × 1014 photons s−1 to a high‐energy‐resolution beam of ΔE/E ≃ 1.5 × 10−4; both modes share a constant beam exit. With a set of Kirkpatrick–Baez (KB) mirrors, the X‐ray beam is focused to the farthest SAXS detector position, 52 m from the source. A downstream four‐bounce crystal collimator, comprising two sets of Si(311) double crystals arranged in a dispersive configuration, optionally collimate the DCM (vertically diffracted) beam in the horizontal direction for ultra‐SAXS with a minimum scattering vector q down to 0.0004 Å−1, which allows resolving ordered d‐spacing up to 1 µm. A microbeam, of 10–50 µm beam size, is tailored by a combined set of high‐heat‐load slits followed by micrometre‐precision slits situated at the front‐end 15.5 m position. The second set of KB mirrors then focus the beam to the 40 m sample position, with a demagnification ratio of ∼1.5. A detecting system comprising two in‐vacuum X‐ray pixel detectors is installed to perform synchronized small‐ and wide‐angle X‐ray scattering data collections. The observed beamline performance proves the feasibility of having compound features of high flux, microbeam and ultra‐SAXS in one beamline.
The optical design and performance of the BioSAXS beamline at the Taiwan Photon Source are reported
Background and purpose
Restless legs syndrome (RLS) is an underestimated movement disorder in patients with end‐stage renal disease (ESRD). Several clinical and laboratory factors were inconsistently ...reported to associate with RLS. We aim to perform a large‐scale multicenter study to investigate the possible associated risk factors of RLS in patients with ESRD in Taiwan, a country with the highest incidence of uremia in the world.
Methods
From October 2009 to October 2011, we constitutively recruited 1130 patients with ESRD from 17 hemodialysis centers. Demographic, laboratory data, presence and severity of RLS were collected. Odds ratios (ORs) were estimated by logistic regression models.
Results
We found the prevalence of RLS to be 25.3% in patients with ESRD. Having type 2 diabetes OR = 3.61 (2.27–5.77), P < 0.01, low serum transferrin saturation OR = 1.42 (1.01–2.03), P < 0.05 and duration of dialysis OR = 1.09 (1.03–1.14), P < 0.01 were associated with RLS. In contrast, high serum hemoglobin level was inversely associated with RLS OR = 0.61 (0.40–0.89), P < 0.05. RLS has a significant impact on sleep quality in dialysis patients. Among patients with RLS, history of type 2 diabetes OR = 4.04 (1.65–10.79), P < 0.05, low serum hemoglobin level OR = 5.41 (2.43–13.12), P < 0.01 and duration of dialysis OR = 1.01 (1.01–1.02), P < 0.01 were associated with increased severity of RLS.
Conclusions
Our findings demonstrated that RLS is common in Taiwanese dialysis patients. Clinicians should have a high suspicion for the presence of RLS symptoms in patients with ESRD, especially those with type 2 diabetes, anemia, low serum iron status and long duration of dialysis.
Summary
Background
Epidemiological investigations have examined the association between type 1 diabetes mellitus (T1DM) and atopic disease, but have obtained conflicting results.
Objectives
To ...analyse the association between T1DM and atopic dermatitis (AD) in a population‐based, retrospective cohort study that investigated the hypothesis that childhood T1DM is a risk factor for subsequent AD.
Methods
From claims data of the National Health Insurance programme of Taiwan, we identified 3386 patients with T1DM newly diagnosed from 1998 to 2011 and 12 725 randomly selected controls without T1DM. These were frequency matched by age, sex and year of diagnosis. Both cohorts were followed up until the end of 2011 to evaluate the AD risk. We used Cox proportional hazards regression models to analyse the risk of AD.
Results
The overall incidence rate of AD was 1·40‐fold (significantly) higher in the T1DM cohort than in the non‐T1DM cohort (3·31 vs. 2·35 per 1000 person years). After adjustment for potential risk factors, the overall risk of AD remained higher in the T1DM cohort adjusted hazard ratio (HR) 1·76, 95% confidence interval (CI) 1·29–2·39 than in those without T1DM. Compared with the non‐T1DM cohort, the patients with T1DM with more emergency room visits (adjusted HR 30·1, 95% CI 18·7–48·5) or hospitalizations (adjusted HR 70·3, 95% CI 45·6–114·5) had a higher risk of subsequent AD.
Conclusions
This nationwide, retrospective cohort study demonstrates that childhood T1DM may increase the risk of AD.
What's already known about this topic?
Some studies have reported that atopic dermatitis (AD) is associated with a lower risk of type 1 diabetes mellitus (T1DM).
An inverse association was theorized between T1DM and AD because the T‐helper 1/2 immune responses of these two diseases are mutually inhibitory.
What does this study add?
This nationwide, retrospective cohort study demonstrates that childhood T1DM may increase the risk of AD.
The overall AD incidence rate was 1·40‐fold (significantly) higher in the T1DM cohort than in the non‐T1DM cohort (3·31 vs. 2·35 per 1000 person years).
Linked Comment: Ezzedine and Barbarot, Br J Dermatol 2016; 174: 16.
Plain language summary available online
This nationwide study aimed to provide risk estimates for a panel of infections subsequent to pyogenic liver abscesses (PLA) in Taiwan. In this study, we selected 12 050 patients diagnosed with PLA ...as our study cohort and 60 250 non-PLA patients as our comparison cohort. We individually tracked each subject for a 1-year period beginning with their index date to identify those who were subsequently diagnosed with any of the following infections: pneumonia, endophthalmitis, septic pulmonary embolism, pulmonary abscess, pleural empyema, meningitis, abscess of prostate, renal and perinephric abscess, epidural spinal abscess, osteomyelitis, necrotizing fasciitis, splenic abscess, psoas abscess and infectious endocarditis. We found that during the 1-year follow-up period, the subjects with PLA had a consistently higher incidence of all types of infections than comparison subjects. In particular, compared with subjects without PLA, the adjusted hazard ratios (HR) of pulmonary abscess, pleural empyema, renal and perinephric abscess, epidural spinal abscess and splenic abscess were 26.71, 18.56, 43.21, 51.32 and 126.51, respectively. We further analysed the HR of extra-hepatic Klebsiella pneumoniae infections among patients with PLA caused by K. pneumoniae. We found that the HR was higher for 12 of the 15 analysed extra-hepatic infections after restricting the analysis to only infections with K. pneumoniae aetiologies.
Inflammatory markers such as interleukin (IL)-6 and tumour necrosis factor-alpha (TNF-α) are elevated in dialysis patients and can predict cardiovascular events and all-cause mortality. Endotoxin is ...an important source and also another marker of inflammation in patients with chronic kidney disease. The aim of this study was to evaluate the impact of oral probiotics on serum levels of endotoxemia and cytokines in peritoneal dialysis (PD) patients. The decline of residual renal function, peritonitis episodes, and cardiovascular events were also recorded. From July 2011 to June 2012, a randomised, double-blind, placebo-controlled trial was conducted in PD patients. The intervention group received one capsule of probiotics containing 109 cfu Bifobacterium bifidum A218, 109 cfu Bifidobacterium catenulatum A302, 109 cfu Bifidobacterium longum A101, and 109 cfu Lactobacillus plantarum A87 daily for six months, while the placebo group received similar capsules containing maltodextrin for the same duration. Levels of serum TNF-α, interferon gamma, IL-5, IL-6, IL-10, IL-17, and endotoxin were measured before and six months after intervention. 39 patients completed the study (21 in the probiotics group and 18 in the placebo group). In patients receiving probiotics, levels of serum TNF-α, IL-5, IL-6, and endotoxin significantly decreased after six months of treatment, while levels of serum IL-10 significantly increased. In contrast, there were no significant changes in levels of serum cytokines and endotoxin in the placebo group after six months. In addition, the residual renal function was preserved in patients receiving probiotics. In conclusion, probiotics could significantly reduce the serum levels of endotoxin, pro-inflammatory cytokines (TNF-α and IL-6), IL-5, increase the serum levels of anti-inflammatory cytokine (IL-10), and preserve residual renal function in PD patients.
A significant consequence of Typhoon Morakot in August 2009 was the production of vast volumes of driftwood in Pacific Asia. We have quantified the flux of this coarse woody debris (CWD) to the ...oceans from typhoon-triggered landslides in Taiwan, where Morakot made landfall, by combining remote sensing (using FORMOSAT-2 imagery and aerial photography), analysis of forest biomass, and field observations. A total of 3.8–8.4 TgCWD was transported to the oceans, carrying 1.8–4.0 Tg of organic carbon. In addition to the local effects on the marine and coastal environment from such a highly concentrated flux of carbon and nutrients, storm-driven mobilization of CWD may represent a significant, if infrequent, transfer of terrestrial biomass to the oceans. If the frequency of relatively rare, extreme storms such as Morakot increases in a changing climate, this transport mechanism may play an important role in feedbacks between global climate, storm intensity, and carbon cycling.
Conventionally, acute myeloid leukemia (AML) patients are categorized into good-, intermediate- and poor-risk groups according to cytogenetic changes. However, patients with intermediate-risk ...cytogenetics represent a largely heterogeneous population regarding treatment response and clinical outcome. In this study, we integrated cytogenetics and molecular mutations in the analysis of 318 patients with de novo non-M3 AML who received standard chemotherapy. According to the mutation status of eight genes, including NPM1, CEBPA, IDH2, RUNX1, WT1, ASXL1, DNMT3A and FLT3, that had prognostic significance, 229 patients with intermediate-risk cytogenetics could be refinedly stratified into three groups with distinct prognosis (P<0.001); patients with good-risk genotypes had a favorable outcome (overall survival, OS, not reached) similar to those with good-risk cytogenetics, whereas those with poor-risk genotypes had an unfavorable prognosis (OS, 10 months) similar to those with poor-risk cytogenetics (OS, 13.5 months), and the remaining patients with other genotypes had an intermediate outcome (OS, 25 months). Integration of cytogenetic and molecular profiling could thus reduce the number of intermediate-risk AML patients from around three-fourth to one-fourth. In conclusion, integration of cytogenetic and molecular changes improves the prognostic stratification of AML patients, especially those with intermediate-risk cytogenetics, and may lead to better decision on therapeutic strategy.
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