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.
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.
Four 2-(styryl)triphenylene derivatives (TSs) were synthesized for deep-blue dopant materials. By using a pyrene-containing compound, DMPPP, as the host, the TS-doped devices exhibited significant ...delayed fluorescence via triplet-triplet annihilation, providing the highest quantum efficiency of 10.2% and a current efficiency of 12.3 cd A(-1).
Objectives
This study aims to assess the effectiveness of a multidomain intervention program on the change in functional status of hospitalized older adults.
Design
This single-arm, prospective, ...non-randomized interventional study investigates the efficacy of a multidomain interventional program including cognitive stimulation activity, simple exercises, frailty education, and nutrition counseling.
Setting and Participants
At a tertiary hospital in southern Taiwan, 352 eligible patients were sequentially enrolled. Included patients were aged ≥65 years (mean age, 79.6 ± 9.0 years; 62% male), scored 3–7 on the Clinical Frailty Scale (CFS), and were hospitalized in the geriatric acute ward.
Intervention
Those receiving standard care (physical rehabilitation and nutrition counseling) during January–July 2019 composed the historical control group. Those receiving the multidomain intervention during August–December 2019 composed the intervention group.
Measurements
The primary outcome was the change in activities of daily life (ADL) and frailty status, as assessed by Katz Index and Clinical Frailty Scale, with using the generalized estimating equation model. The length of hospital stay, medical costs, and re-admission rates were secondary outcomes.
Results
Participants undergoing intervention (n = 101; 27.9%) showed greater improvements in the ADL and CFS during hospitalization (ADL adjusted estimate, 0.61; 95% CI, 0.11–1.11; p = 0.02; CFS adjusted estimate, −1.11; 95% CI, −1.42–−0.80; p < 0.01), shorter length of hospital stay (adjusted estimate, -5.00; 95% CI, −7.99–−2.47; p < 0.01), lower medical costs (adjusted estimate, 0.58; 95% CI, 0.49–0.69; p < 0.01), and lower 30- and 90-day readmission rates (30-day adjusted OR aOR, 0.12; 95% CI, 0.27–0.50; p < 0.01; 60-day aOR, 0.04; 95% CI, 0.01–0.33; p < 0.01) than did controls.
Conclusions
Participation in the multidomain intervention program during hospitalization improved the functional status and decreased the hospital stay length, medical costs, and readmission rates of frail older people.
Although the clinical features of the Isocitrate dehydrogenase 2 (IDH2) mutation in acute myeloid leukemia (AML) have been characterized, its prognostic significance remains controversial and its ...stability has not been investigated. We analyzed 446 adults with primary non-M3 AML and found IDH2 R172, R140 and IDH1 R132 mutations occurred at a frequency of 2.9, 9.2 and 6.1%, respectively. Compared with wild-type IDH2, mutation of IDH2 was associated with higher platelet counts, intermediate-risk or normal karyotype and isolated +8, but was inversely correlated with expression of HLA-DR, CD34, CD15, CD7 and CD56, and was mutually exclusive with WT1 mutation and chromosomal translocations involving core-binding factors. All these correlations became stronger when IDH1 and IDH2 mutations were considered together. Multivariate analysis revealed IDH2 mutation as an independent favorable prognostic factor. IDH2(-)/FLT3-ITD(+) genotype conferred especially negative impact on survival. Compared with IDH2 R140 mutation, IDH2 R172 mutation was associated with younger age, lower white blood cell count and lactate dehydrogenase level, and was mutually exclusive with NPM1 mutation. Serial analyses of IDH2 mutations at both diagnosis and relapse in 121 patients confirmed high stability of IDH2 mutations. In conclusion, IDH2 mutation is a stable marker during disease evolution and confers favorable prognosis.
Biomarkers that predict disease progression might assist the development of better therapeutic strategies for aggressive cancers, such as ovarian cancer. Here, we investigated the role of collagen ...type XI alpha 1 (COL11A1) in cell invasiveness and tumor formation and the prognostic impact of COL11A1 expression in ovarian cancer. Microarray analysis suggested that COL11A1 is a disease progression-associated gene that is linked to ovarian cancer recurrence and poor survival. Small interference RNA-mediated specific reduction in COL11A1 protein levels suppressed the invasive ability and oncogenic potential of ovarian cancer cells and decreased tumor formation and lung colonization in mouse xenografts. A combination of experimental approaches, including real-time RT-PCR, casein zymography and chromatin immunoprecipitation (ChIP) assays, showed that COL11A1 knockdown attenuated MMP3 expression and suppressed binding of Ets-1 to its putative MMP3 promoter-binding site, suggesting that the Ets-1-MMP3 axis is upregulated by COL11A1. Transforming growth factor (TGF)-beta (TGF-β1) treatment triggers the activation of smad2 signaling cascades, leading to activation of COL11A1 and MMP3. Pharmacological inhibition of MMP3 abrogated the TGF-β1-triggered, COL11A1-dependent cell invasiveness. Furthermore, the NF-YA-binding site on the COL11A1 promoter was identified as the major determinant of TGF-β1-dependent COL11A1 activation. Analysis of 88 ovarian cancer patients indicated that high COL11A1 mRNA levels are associated with advanced disease stage. The 5-year recurrence-free and overall survival rates were significantly lower (P=0.006 and P=0.018, respectively) among patients with high expression levels of tissue COL11A1 mRNA compared with those with low expression. We conclude that COL11A1 may promote tumor aggressiveness via the TGF-β1-MMP3 axis and that COL11A1 expression can predict clinical outcome in ovarian cancer patients.
The present case-control study was to investigate the relationships of plasma leptin level and anthropometric measures of adiposity with the risk of breast cancer. Questionnaire information, ...anthropometric measures and blood samples were taken before treatment from 297 incident cases with breast cancer and 593 controls admitted for health examination at the Tri-Service General Hospital, Taipei, between 2004 and 2006. Plasma levels of leptin were measured by RIA. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for assessing the associations. Overall, higher leptin concentrations were significantly associated with an increased risk of breast cancer (OR (95% CI) for top vs bottom tertile of leptin was 1.63 (1.07-2.49), P(trend)=0.009). Waist circumference was a significant anthropometric factor for breast cancer in both pre- and postmenopausal women. Furthermore, the associations of leptin with breast cancer risk remained after adjustment for obesity indices. These results suggest that leptin may have an independent role in breast tumorigenesis. Regardless of the impact of circulating leptin, more research is needed to elucidate molecular mechanisms and local leptin levels that are critical for the development of breast cancers.
The Tonga volcano eruption of 15 January 2022 unleashed a variety of atmospheric perturbations, coinciding with the recovery-phase of a geomagnetic storm. The ensuing thermospheric variations created ...rare display of extreme poleward-expanding conjugate plasma bubbles seen in the rate of total electron content index over 100–150°E, reaching ∼40°N geographic latitude. This is associated with fluctuations in FORMOSAT-7/COSMIC-2 (F7/C2) ion-density measurements and spread-F in ionograms. Preceding to this, an unusually strong pre-reversal enhancement (PRE) occurred in the global ionospheric specification (GIS) electron density profiles derived from F7/C2 observations. The GIS also revealed a decrease of equatorial ionization anomaly (EIA) crest density due to the storm impact. Reduced E-region conductivity by volcano-induced waves and enhanced F-region wind, further accelerated by reduced ion-drag over the EIA, apparently intensified the PRE.
Accompanied with the strong PRE, volcano-induced seed perturbations triggered the super plasma bubble activity.
A new group of thin film metallic glasses (TFMGs) have been reported to exhibit properties different from conventional crystalline metal films, though their bulk forms are already well-known for high ...strength and toughness, large elastic limits, and excellent corrosion and wear resistance because of their amorphous structure. In recent decades, bulk metallic glasses have gained a great deal of interest due to substantial improvements in specimen sizes. In contrast, much less attention has been devoted to TFMGs, despite the fact that they have many properties and characteristics, which are not readily achievable with other types of metallic or oxide films. Nevertheless, TFMGs have been progressively used for engineering applications and, thus, deserve to be recognized in the field of thin film coatings. This article will thus discuss both properties and applications of TFMGs including a review of solid-state amorphization upon annealing, the glass-forming ability improvement due to thin film deposition, and mechanical properties, including residual stress, hardness and microcompression, adhesion, and wear resistance. Potential applications and simulations will also be discussed.
Summary
Background HLA‐Cw*06 has a strong influence on the clinical features and the susceptibility to psoriasis in different ethnicities. It is also used as a biomarker to predict the therapeutic ...efficacy of biologics, with inconsistent results. Additionally, most Asian patients with psoriasis do not carry HLA‐Cw*06.
Objectives To determine additional HLA alleles which confer susceptibility or affect the severity of psoriasis in Chinese Han individuals. In addition, the potential of using HLA to predict treatment outcomes was also investigated.
Methods We conducted a case–control association study in 199 Chinese patients with psoriasis and 200 unrelated healthy controls. HLA‐B and HLA‐C genotyping was performed and correlated with the therapeutic efficacy of the biologics, including alefacept, efalizumab, etanercept and ustekinumab. Patients with psoriasis were divided into group A (high‐need patients with moderate to severe psoriasis) and B (general patients with psoriasis).
Results The frequencies of HLA‐B*60, HLA‐B*75, HLA‐Cw*06 and HLA‐Cw*10 were significantly increased in patients with psoriasis compared with the healthy controls. However, the prevalence of HLA‐Cw*06 was lower in group A compared with group B (6% vs. 17%, Pc = 0·04). HLA‐B*46 was found to be strongly associated with group A but not with group B patients with psoriasis. HLA‐Cw*01/HLA‐B*46 was also identified as a risk haplotype for Chinese patients with psoriasis, compatible with the results in Thais. Significant differences in response to biologics were observed between HLA‐Cw*01+ and HLA‐Cw*01− individuals in the alefacept treatment group, and between HLA‐B*37+ and HLA‐B*37−, and HLA‐B*58+ and HLA‐B*58− individuals in the efalizumab treatment group.
Conclusions In addition to HLA‐Cw*06, the HLA‐Cw*01/HLA‐B*46 haplotype was also increased in Chinese patients with psoriasis. High‐need patients with psoriasis had a lower frequency of HLA‐Cw*06 but a higher prevalence of HLA‐B*46 compared with general patients with psoriasis in our population.
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