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Essential thrombocythemia (ET) cases without canonical JAK2, CALR, or MPL mutations, that is, triple‐negative (TN) ET, have been found in 10%–20% of ET cases. Owing to the limited number of TN ET cases, its clinical significance remains unclear. This study evaluated TN ET's clinical characteristics and identified novel driver mutations. Among 119 patients with ET, 20 (16.8%) had no canonical JAK2/CALR/MPL mutations. Patients with TN ET tended to be younger and had lower white blood cell counts and lactate dehydrogenase values. We identified putative driver mutations in 7 (35%): MPL S204P, MPL L265F, JAK2 R683G, and JAK2 T875N were previously reported as candidate driver mutations in ET. Moreover, we identified a THPO splicing site mutation, MPL*636Wext*12, and MPL E237K. Four of the seven identified driver mutations were germline. Functional studies on MPL*636Wext*12 and MPL E237K revealed that they are gain‐of‐function mutants that increase MPL signaling and confer thrombopoietin hypersensitivity with very low efficiency. Patients with TN ET tended to be younger, although this was thought to be due to the inclusion of germline mutations, hereditary thrombocytosis. Accumulating the genetic and clinical characteristics of noncanonical mutations may help future clinical interventions in TN ET and hereditary thrombocytosis. [ABSTRACT FROM AUTHOR]

The article focuses on findings of a study on clinical significance of cutaneous adverse reaction to mogamulizumab in relapsed or refractory adult T-cell leukaemia-lymphoma. It states that mogamulizumab is a humanized monoclonal antibody against CC chemokine receptor 4, and mentions that in the patients who received more than 4 cycles of mogamulizumab, the overall survival for the patients who developed cutaneous adverse reactions (CARs).

In the FIRST trial ( MM-020), lenalidomide plus low-dose dexamethasone (Rd) reduced the risk of disease progression or death compared with combination melphalan-prednisone-thalidomide. As the FIRST trial did not include any Japanese patients, the efficacy and safety of continuous treatment with Rd was evaluated in 26 Japanese patients with newly diagnosed multiple myeloma ( NDMM) in a single-arm, multicenter, open-label phase II trial ( MM-025). Patients received lenalidomide on days 1-21 of each 28-day cycle, with a starting dose of 25 mg/day (dose adjusted for renal impairment), and 40 mg/day dexamethasone (dose adjusted for age) on days 1, 8, 15 and 22 of each 28-day cycle until disease progression or discontinuation for any reason. In the efficacy evaluable population, overall response rate was 87.5%, including 29.2% of patients who achieved a complete response/very good partial response. Median durations of response, progression-free survival and overall survival have not been reached. The most common grade 3-4 adverse events were neutropenia (23%) and anemia (19%). The efficacy and safety of Rd were consistent with data from larger studies, including the FIRST trial, thereby supporting the use of Rd continuous in Japanese patients with NDMM who are ineligible for stem cell transplantation. [ABSTRACT FROM AUTHOR]

Ghrelin is a novel gastric peptide identified in 1999 as a 'hunger hormone'. Plasma ghrelin level is decreased in human obesity. Factors associated with ghrelin have been mainly investigated in western countries where the prevalence of obesity is high. The aim of this study is to examine factors associated with plasma ghrelin in a Japanese general population where obesity is not so common. Fasting ghrelin levels were measured by ELISA in 638 subjects in 2005-2007. We measured body mass index (BMI), waist circumference and blood pressure. Blood was drawn in the morning after a 12-h fast for determinations of ghrelin, lipid, glucose (FPG), insulin, estimated glomerular filtration rate (eGFR) and uric acid levels. Univariate and multiple stepwise regression analyses were performed to find out factors associated with ghrelin. In our population, the mean BMI was 23·8 kg/m, indicating a nonobese population. Results of univariate analysis showed that age ( P < 0·001), BMI ( P < 0·001), waist ( P < 0·001), triglycerides ( P < 0·01), FPG ( P < 0·01), insulin ( P < 0·001) and uric acid ( P < 0·05) were inversely associated with ghrelin. High-density lipoprotein (HDL) cholesterol ( P < 0·001) and eGFR ( P < 0·05) were positively associated with ghrelin. Men had lower ghrelin levels than women ( P < 0·001). Results of the multiple stepwise regression analysis revealed that age ( P < 0·001; inversely), female gender ( P < 0·001), insulin ( P < 0·001; inversely), HDL cholesterol ( P = 0·005), BMI ( P = 0·01; inversely) and uric acid ( P = 0·045; inversely) were significantly and independently associated with ghrelin. The present study demonstrated that age and gender affected plasma ghrelin levels more than BMI. This may well be because of the low prevalence of overweight in our population. [ABSTRACT FROM AUTHOR]

High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) are strong predictors of atherosclerosis. Statin-induced changes in the ratio of LDL-C to HDL-C (LDL-C/HDL-C) predicted atherosclerosis progression better than LDL-C orHDL-C alone. However, the best predictor of subclinical atherosclerosis remains unknown. Our objective was to investigate this issue by measuring changes in carotid intima-media thickness (IMT). A total of 1,920 subjects received health examinations in 1999, and were followed up in 2007. Changes in IMT (follow-up IMT/baseline IMT × 100) were measured by ultrasonography. Our results showed that changes in IMT after eight years were significantly related to HDL-C (inversely,P < 0.05) and to LDL-C/HDL-C ratio (P < 0.05).When the LDL-C/HDL-C ratios were divided into quartiles, analysis of covariance showed that increases in the ratio were related to IMT progression (P < 0.05). This prospective study demonstrated the LDL-C/HDL-C ratio is a better predictor of IMT progression than HDL-C or LDL-C alone. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To determine whether serum dehydroepiandrosterone sulfate (DHEAS) levels could predict longevity in residents. DESIGN: Prospective community-based cohort study. SETTING: Community. PARTICIPANTS: Nine hundred forty subjects (396 men, 544 women; aged 21 to 88) underwent a health examination in 1978. Serum DHEAS levels were measured according to radioimmunoassay at baseline in all subjects, and subjects were followed periodically until 2005. RESULTS: Baseline DHEAS levels were higher in men than in women and decreased with age in both sexes. In a Cox proportional hazards model, age, DHEAS (inversely), blood pressure, and fasting plasma glucose were significantly associated with shorter longevity in men but not in women. Of these variables, high DHEAS levels in men were the strongest predictor of longevity (β=−2.032, hazard ratio=0.131, 95% confidence interval=0.029–0.584 in the Cox proportional hazards model after adjustment for age). The Kaplan-Meier survival curve, stratified according to tertiles of DHEAS levels, in men after adjustments for age, systolic blood pressure, and fasting plasma glucose showed significantly (log-rank stat =10.6; P<.001) greater longevity in the highest group (200 μg/dL) than in the moderate (130–199 μg/dL) or lowest groups (129 μg/dL). CONCLUSION: This 27-year study in a community-based cohort indicated that DHEAS level may be a predictor of longevity in men, independent of age, blood pressure, and plasma glucose. [ABSTRACT FROM AUTHOR]