© F e r r a t a S t o r t i F o u n d a t i o nmg/kg/day for at least 6 months), and methylprednisolone (2 mg/kg/day for 5 days) with subsequent halving of the dose every week until discontinuation on day 28. The dose of cyclosporine was adjusted to maintain whole blood concentrations between 150 and 250 ng/mL. Hematologic response was evaluated at 3 and 6 months after the start of therapy. The definitions of complete response, partial response, and relapse have been previously published.1 Briefly, a complete response was defined for all patients as a neutrophil count more than 1.5×10 9 /L, a platelet count more than 100×10 9 /L, and a hemoglobin level more than 11.0 g/dL. A partial response was defined as a neutrophil count more than 0.5×10 9 /L, a platelet count more than 20×10 9 /L, a hemoglobin level more than 80 g/L and no requirement for blood transfusions. Second-line therapies for non-responders to the first immunosuppressive therapy depended on the policies of the individual hospitals.The Mann-Whitney U test was used to compare continuous variables and Pearson χ 2 test was used for categorical variables. Survival rates were calculated using two methods: one indicated when data on patients were censored at the time of stem cell transplantation (transplant-free survival) and the other indicated when data on patients were not censored at the time of transplantation (overall survival).Survival rates were analyzed using the Kaplan-Meier method. Treatment groups were compared with the long-rank test. Cox proportional hazards models were used to assess which factors could predict response as well as risk factors for survival using both univariate and multivariate analyses. The estimated magnitude of the hazard ratio (HR) is shown along with the 95% confidence interval (95% CI). P values less than 0.05 are considered statistically significant.This study was approved by ethics committees of the Catholic University of Korea, Nagoya University Graduate School of Medicine, and Chinese Academy of Medical Science and Pekin Union Medical College. ResultsThe patients' characteristics are shown in Table 1. Overall, 455 patients fulfilled the eligibility criteria; 297 patients received horse ATG and 158 patients received rabbit ATG. The median follow-up periods were 82 months (range, 1 to 215 months) in the horse ATG group and 20 months (range, 1 to 182 months) in the rabbit ATG group. The median age at diagnosis was significantly older in the horse ATG group than in the rabbit ATG group. In addition, percentages of males, very severe aplastic anemia, and hepatitis-associated aplastic anemia were significantly higher in the horse ATG group than in the rabbit ATG group (Table 1).We compared hematologic responses between the horse ATG group and the rabbit ATG group (Table 2). After 3 months, in the horse ATG group, 24 (8%) patients had achieved a complete response and 112 (38%) had achieved a partial response, for an overall response rate of 46%. In the rabbit ATG group, 9 (6%) patients achieved a complete respons...

The aim of this study was to describe the mutational characteristics in Korean hereditary spherocytosis (HS) patients. Relevant literatures including genetically confirmed cases with well-documented clinical summaries and relevant information were also reviewed to investigate the mutational gene- or domain-specific laboratory and clinical association. Twenty-five HS patients carried one heterozygous mutation of ANK1 (n = 13) or SPTB (n = 12) but not in SPTA1, SLC4A1, or EPB42. Deleterious mutations including frameshift, nonsense, and splice site mutations were identified in 91% (21/23), and non-hotspot mutations were dispersed across multiple exons. Genotype-phenotype correlation was clarified after combined analysis of the cases and the literature review; anemia was most severe in HS patients with mutations on the ANK1 spectrin-binding domain (p < 0.05), and SPTB mutations in HS patients spared the tetramerization domain in which mutations of hereditary elliptocytosis and pyropoikilocytosis are located. Splenectomy (17/75) was more frequent in ANK1 mutant HS (32%) than in HS with SPTB mutation (10%) (p = 0.028). Aplastic crisis occurred in 32.0% of the patients (8/25; 3 ANK1 and 5 SPTB), and parvovirus B19 was detected in 88%. The study clarifies ANK1 or SPTB mutational characteristics in HS Korean patients. The genetic association of laboratory and clinical aspects suggests comprehensive considerations for genetic-based management of HS.

BackgroundAlthough the proportion of Pseudomonas aeruginosa infections has reduced after the introduction of antibiotics with anti-pseudomonal effects, P. aeruginosa bacteremia still causes high mortality in immunocompromised patients. This study determined the clinical characteristics and outcomes of P. aeruginosa bacteremia and the antibiotic susceptibilities of strains isolated from febrile neutropenic patients.MethodsThirty-one febrile neutropenic children and adolescents with underlying hematologic/oncologic disorders diagnosed with P. aeruginosa bacteremia between 2011 and 2016 were enrolled in the study. Their medical records were retrospectively reviewed to evaluate the demographic and clinical characteristics. Antibiotic susceptibility rates of the isolated P. aeruginosa to eight antibiotic categories (anti-pseudomonal penicillin, anti-pseudomonal penicillin and β-lactamase inhibitor combination, anti-pseudomonal cephalosporin, monobactam, carbapenem, aminoglycoside, fluoroquinolone, and colistin) were also determined. Among the investigated factors, risk factors for mortality and infections by a multidrug-resistance (MDR) strain were determined.ResultsThirty-six episodes of P. aeruginosa bacteremia were identified. The mean age of the enrolled patients was 9.5 ± 5.4 years, and 26 (72.2%) episodes occurred in boys. Acute myeloid leukemia (41.7%) and acute lymphoblastic leukemia (33.3%) were the most common underlying disorders. The 30-day mortality was 38.9%, and 36.1% of the episodes were caused by MDR strains. The deceased patients were more likely to experience breakthrough infection (P = 0.036) and bacteremia (P = 0.005) due to MDR strains when compared with the patients who survived. The survived patients more likely received appropriate empirical antibiotic therapy (P = 0.024) and anti-pseudomonal β-lactam and aminoglycoside combination therapy (P = 0.039) compared with the deceased patients. The antibiotic susceptibility rates of the isolated P. aeruginosa strains were as follows: piperacillin/tazobactam, 67.6%; meropenem, 72.2%; and amikacin, 100%.ConclusionsMortality due to P. aeruginosa bacteremia remained at 38.9% in this study, and more than one-third of the isolated strains were MDR. In this context, empirical antibiotic combination therapy to expand the antibiotic spectrum may be a strategy to reduce mortality due to P. aeruginosa bacteremia in febrile neutropenic patients.

BackgroundThe rate of urinary tract infections (UTIs) due to extended-spectrum β-lactamase (ESBL)-producing bacterial strains requiring carbapenem therapy has been increasing in children. This study was conducted to evaluate the effect of non-carbapenem antibiotic therapy on childhood UTIs caused by ESBL-producing Escherichia coli or Klebsiella pneumoniae.MethodsMedical records of children diagnosed with febrile UTIs due to E. coli or K. pneumoniae between 2010 and 2014 were retrospectively reviewed. The enrolled children were divided into two groups: the ESBL group and the non-ESBL group. Clinical characteristics and therapeutic responses were compared between the two groups.ResultsA total of 211 episodes of UTI (204 caused by E. coli; seven caused by K. pneumoniae) were identified in 205 children. Twenty-two (10.4 %) episodes were categorized into the ESBL group. There was no significant difference in the type of antibiotic administered between the two groups. No carbapenems were administered; however, aminoglycosides were administered for 79.1 % of the total episodes. Although empirical antibiotics were appropriate for more episodes in the non-ESBL group compared with the ESBL group (100.0 % vs. 90.9 %, p = 0.011), there were no significant differences in the frequency of defervescence, bacterial eradication from the urine, acute pyelonephritis and vesicoureteral reflux or fever duration between the two groups.ConclusionsNon-carbapenem antibiotics showed favourable therapeutic effects on childhood UTIs caused by ESBL-producing strains. Aminoglycosides can be an alternative to carbapenems in such cases.

Marrow stromal cells (MSC) produce a microenvironment supporting hematopoiesis and may contribute immune tolerance because of low immunogenicity and the suppressive effect of alloreactivity. We investigated whether cotransplantation of MSC could prevent lethal graft-versus-host disease (GVHD) in major histocompatibility complex mismatched allogeneic murine hematopoietic stem cell transplantation (HSCT) using female BALB/c (H-2d, recipient) and C3H/He (H-2k, donor) mice. MSC were obtained from C3H/He bone marrow cells (BMC). MSC and irradiated BALB/c splenocytes (SP) were cocultured with C3H/He SP or BMC. Nonirradiated MSC did not inhibit the proliferation of alloantigen-stimulated BMC and SP. However, irradiated MSC suppressed the proliferation of alloantigen-stimulated SP at a level comparable with that of immunosuppressive agents, and the suppression by MSC was reversed to a significant degree by interleukin 2. Lethally irradiated BALB/c mice received transplants of donor cells according to the following experimental groups (group A, BMC only; group B, BMC and SP; group C, BMC, SP, and MSC; group D, BMC and MSC). The survival rate in group D was higher than in the other groups (P = .0057), and the clinical GVHD scores and serum levels of interferon-gamma were low in group D. Our results suggest that cotransplantation of MSC in HSCT prevents lethal GVHD, possibly by immune modulation.