J-H Lee

Comparison of outcomes between autologous and allogeneic hematopoietic stem cell transplantation for peripheral T-cell lymphomas with central review of pathology

Comparison of outcomes between autologous and allogeneic hematopoietic stem cell transplantation for peripheral T-cell lymphomas with central review of pathology

A phase 1b/2b multicenter study of oral panobinostat plus azacitidine in adults with MDS, CMML, or AML with ⩽ 30% blasts.

Treatment with azacitidine (AZA), a demethylating agent, prolonged overall survival (OS) vs conventional care in patients with higher-risk myelodysplastic syndromes (MDS). As median survival with monotherapy is <2 years, novel agents are needed to improve outcomes. This phase 1b/2b trial (n=113) was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of panobinostat (PAN)+AZA (phase 1b) and evaluate the early efficacy and safety of PAN+AZA vs AZA monotherapy (phase 2b) in patients with higher-risk MDS, chronic myelomonocytic leukemia or oligoblastic acute myeloid leukemia with <30% blasts. The MTD was not reached; the RP2D was PAN 30u2009mg plus AZA 75u2009mg/m2. More patients receiving PAN+AZA achieved a composite complete response ([CR)+morphologic CR with incomplete blood count+bone marrow CR (27.5% (95% CI, 14.6–43.9%)) vs AZA (14.3% (5.4–28.5%)). However, no significant difference was observed in the 1-year OS rate (PAN+AZA, 60% (50–80%); AZA, 70% (50–80%)) or time to progression (PAN+AZA, 70% (40–90%); AZA, 70% (40–80%)). More grade 3/4 adverse events (97.4 vs 81.0%) and on-treatment deaths (13.2 vs 4.8%) occurred with PAN+AZA. Further dose or schedule optimization may improve the risk/benefit profile of this regimen.

Triglycerides/glucose index is a useful surrogate marker of insulin resistance among adolescents

Objectives:Our aim was to investigate the association between the triglycerides/glucose index (TyG index) and the homeostasis model assessment-estimated insulin resistance (HOMA-IR) in the prediction of insulin resistance (IR) among adolescents.Methods:We conducted a cross-sectional study among 221 Korean adolescents (168 males and 53 females aged 9–13 years) from May to June 2014 in Chung-ju city. The TyG index was calculated as ln [triglycerides (mgu2009dl−1) × fasting glucose (mgu2009dl−1)/2]. IR was defined using HOMA-IR >95th percentile for age and sex.Results:In the IR group, weight, body mass index (BMI), waist circumference, body fat, fasting insulin, fasting plasma glucose, triglyceride levels and triglycerides/high-density lipoprotein cholesterol (TG/HDL-C) were significantly higher than that in the non-IR group. The TG index was significantly different between the IR group (n=22) and non-IR group (n=199), at 8.43±0.45 and 8.05±0.41, respectively (P<0.001). The TyG index was well correlated with HOMA-IR (r=0.41; P<0.001) and showed a strong positive association with TG/HDL-C (r=0.84; P<0.001). The cut-off of the TyG index for diagnosis of insulin resistance was 8.18.Conclusions:The TyG index is a simple, cost-effective surrogate marker of insulin resistance among adolescents compared with HOMA-IR.

Single monosomy as a relatively better survival factor in acute myeloid leukemia patients with monosomal karyotype.

Monosomal karyotype (MK) defined by either ⩾2 autosomal monosomies or single monosomy with at least one additional structural chromosomal abnormality is associated with a dismal prognosis in patients with acute myeloid leukemia (AML). It was detected in 174 of 3041 AML patients in South Korean Registry. A total of 119 patients who had received induction therapy were finally analyzed to evaluate the predictive factors for a positive prognosis. On multivariate analysis, single monosomy, the absence of abn(17p), ⩾10% of cells with normal metaphase and the achievement of a complete remission (CR) after induction therapy were significant factors for more favorable outcomes. Especially, single monosomy remained as a significantly independent prognostic factor for superior survival in both patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) in CR and who did not. Allo-HSCT in CR improved overall survival significantly only in patients with a single monosomy. Our results suggest that MK-AML may be biologically different according to the karyotypic subtype and that allo-HSCT in CR should be strongly recommended to patients with a single monosomy. For other patients, more prudent treatment strategies should be examined. Furthermore, the biological mechanism by which a single monosomy influences survival should be investigated.

Serial serum cholinesterase activities as a prognostic factor in organophosphate poisoned patients

Objective Organophosphate poisoning is a serious clinical entity and of considerable morbidity and mortality. Several factors have been identified to predict outcomes of organophosphate poisoning. This investigation aims to identify the relationship between the dynamics of serum cholinesterase (SChE) activity and mortality. Methods In this retrospective study, medical records of all patients with acute organophosphate poisoning were reviewed from January 2001 to December 2009. Clinical features, SChE activity, Glasgow Coma Scale, laboratory findings, electrocardiogram finding, management and their outcomes were examined. Results A total of 169 patients were included in this study. A total of 55 patients were enrolled. Deceased patients were 8 in number. Absence of an increase in SChE activity was related with mortality in organophosphate poisoned patients (p value=0.036; odds ratio, 5.445; 95% confidence interval, 1.121-26.551). Conclusions The absence of an increase in SChE activity is associated with higher mortality in organophosphate poisoning. The SChE dynamic activity can provide a guide to physicians in the evaluation and management of organophosphate poisoned patients.

Effect of an obesity prevention program focused on motivating environments in childhood: a school-based prospective study

Background/Objectives:There has been an increasing global recognition of the need for effective strategies to prevent and control childhood obesity. In this study, we aimed to identify the effectiveness of an obesity prevention program focused on motivating environments in school.Subjects/Methods:In this school-based, prospective, quasi-experimental study, we enrolled three elementary (fourth graders) and two middle (seventh graders) schools located in Chungju, Korea. We assigned three of the schools to the intervention group and two schools to the control group. The intervention group received 1 year of environmental intervention. Diet- and exercise-related educational video content was provided by internet protocol television services during rest time, and various design materials were painted along the school staircase and hallway to encourage physical activities. Overweight and obese students were recommended to join the summer vacation obesity care program.Results:The final number of total participants was 768 (control 350 and intervention 418). After 1 year of follow-up, there was no significant difference in the overweight/obesity incidence rates and remission rates between the two groups. However, the intervention group showed a greater decrease in the body mass index (BMI) z-score (−0.11 (95% confidence interval (CI) −0.16 to −0.06), P<0.001), increase in height (1.1u2009cm (95% CI 0.8 to 1.4), P<0.001), reduction of body fat, and increase in muscle mass compared with the control group. In addition, blood pressure (BP) was significantly reduced, and significant improvement in physical fitness followed. In subgroup analysis, students of normal weight, boys and younger participants showed the most beneficial results in weight-related outcomes. In addition, the BP reduction was more pronounced in the higher BMI group, boys and older children.Conclusions:A simple environmental intervention could effectively influence children. By adding to previously studied strategies, we can develop a more effective obesity prevention program for children.

Co-receptors are dispensable for tethering receptor-mediated phagocytosis of apoptotic cells

During efferocytosis, phagocytic cells recognize dying cells by receptors binding to ligands specifically exposed on apoptotic cells. Multiple phagocytic receptors and some of their signaling pathways have been identified. However, the downstream pathways of tethering receptors that secure apoptotic cells remain elusive. It is generally assumed that tethering receptors induce signaling to mediate engulfment via interacting with co-receptors or other engulfment receptors located nearby. However, it is poorly understood whether co-receptors for tethering receptors exist during efferocytosis, and, if they do, whether they are indispensable for this process. Here, we address this issue using glycophosphatidylinositol (GPI)-anchored annexin A5 (Anxa5-GPI), an artificial tethering receptor without a putative co-receptor. Phagocytes expressing Anxa5-GPI exhibited enhanced binding of apoptotic cells, resulting in promoted ingestion of apoptotic cells in a phosphatidylserine-dependent manner. Anxa5-GPI-induced phagocytosis of apoptotic cells relied on the known cytoskeletal engulfment machinery but partially depended on the Elmo-Dock-Rac module or the integrin pathway. In addition, Anxa5-GPI-mediated efferocytosis provoked anti-inflammatory responses. Taken together, our work suggests that co-receptors are dispensable for tethering receptor-induced efferocytosis and that tethering receptors mediate the engulfment of apoptotic cells through multiple engulfment signaling pathways.

Discrepancies between the percentage of plasma cells in bone marrow aspiration and BM biopsy: Impact on the revised IMWG diagnostic criteria of multiple myeloma

Discrepancies between the percentage of plasma cells in bone marrow aspiration and BM biopsy: Impact on the revised IMWG diagnostic criteria of multiple myeloma

Role of thymoglobulin in matched sibling allogeneic hematopoietic stem cell transplantation with busulfan and fludarabine conditioning in myeloid malignanicies

In vivo T-cell depletion using anti-thymocyte globulin (ATG) is widely used in allogeneic hematopoietic stem cell transplantation (HSCT) for prophylaxis of GvHD. We investigated the influence of thymoglobulin dose (an ATG) on GvHD following matched sibling donor (MSD) HSCT with a busulfan and fludarabine preparative regimen. Medical records of 180 patients who received MSD HSCT with a conditioning regimen of busulfan, fludarabine, and ATG (BuFluATG) were reviewed retrospectively. The median age was 53 years (range 18–68). Initial diagnoses were acute myeloid leukemia (73.3%) and myelodysplastic syndrome (26.7%). Forty-four and 68 patients (24.4 and 37.7%) experienced acute and chronic GvHD of any grade, respectively. High-dose (⩾4.5u2009mg/kg) ATG was independently associated with decreased risk of acute GvHD (hazard ratio=0.36, 95% confidence interval (CI): 0.15–0.84, P=0.019) compared to low-dose ATG (<4.5u2009mg/kg). Although ATG dose was associated with the risk of acute GvHD, it was not associated with the risk of chronic GvHD in our study. A higher dose (⩾4.5u2009mg/kg) of ATG decreases the risk of acute GvHD but had no significant impact on disease-free survival in MSD HSCT patients conditioned with BuFluATG. The optimal dose of ATG should be further investigated in a large prospective study context.

Holiday Fast-Track Reduced Medical Cost and Length of Emergency Department Stay: Preliminary Report from a Single Secondary Care Hospital

Introduction The aims of this study were to compare the effect of a Holiday Fast-Track (HFT) unit on medical costs and emergency department (ED) length of stay (LOS) associated with low acuity patients attended during the same timeframe in two consecutive years in a single secondary care hospital ED. Methods Two groups (non-HFT vs. HFT), before and after the fast-track unit was implemented, were compared. The HFT unit was operated to improve the flow of low acuity patients, which were defined as the patients classified as level 4 or 5 by the modified Canadian Triage and Acuity Scale. Data were collected from March 1 to April 30, 2011 for the non-HFT group and during the same period in 2012 for the HFT group. Results A total of 894 (431 for non-HFT period and 463 for HFT period) patients of acuity level 4 or 5 visited the ED during the study period. Compared to the non-HFT group, the ED LOS of the HFT group decreased by 27 min and 3.5 min in the patients with acuity levels 4 and 5, respectively (p=0.005 and p=0.003, respectively). Furthermore, total medical costs and laboratory fees were also reduced significantly in the HFT group (p<0.001, p=0.038). However, there was no difference in the other variables between those two groups. Conclusions The HFT system decreases the medical costs and LOS in low acuity patients visiting the ED of a secondary care hospital. (Hong Kong j.emerg.med. 2015;22:84-92)