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Background There has been insufficient evidence regarding a treatment strategy for patients with non-occlusive mesenteric ischemia (NOMI) due to the lack of large-scale studies. We aimed to evaluate the clinical benefit of strategic planned relaparotomy in patients with NOMI using detailed perioperative information. Methods We conducted a multicenter retrospective cohort study that included NOMI patients who underwent laparotomy. In-hospital mortality, 28-day mortality, incidence of total adverse events, ventilator-free days, and intensive care unit (ICU)–free days were compared between groups experiencing the planned and on-demand relaparotomy strategies. Analyses were performed using a multivariate mixed effects model and a propensity score matching model after adjusting for pre-operative, intra-operative, and hospital-related confounders. Results A total of 181 patients from 17 hospitals were included, of whom 107 (59.1%) were treated using the planned relaparotomy strategy. The multivariate mixed effects regression model indicated no significant differences for in-hospital mortality (61 patients [57.0%] in the planned relaparotomy group vs. 28 patients [37.8%] in the on-demand relaparotomy group; adjusted odds ratio [95% confidence interval] = 1.94 [0.78–4.80]), as well as in 28-day mortality, adverse events, and ICU-free days. Significant reduction in ventilator-free days was observed in the planned relaparotomy group. Propensity score matching analysis of 61 matched pairs with comparable patient severity did not show superiority of the planned relaparotomy strategy. Conclusions The planned relaparotomy strategy, compared with on-demand relaparotomy strategy, did not show clinical benefits after the initial surgery of patients with NOMI. Further studies estimating potential subpopulations who may benefit from this strategy are required. Electronic supplementary material The online version of this article (10.1007/s11605-020-04792-3) contains supplementary material, which is available to authorized users.

Historically defined in the European Group for the Immunological Characterization of Leukemias (EGIL) [1], acute bilineal leukemia (ABLL) is characterized by 2 distinct blast populations (e.g. B/my...

A 15-year-old girl with acute lymphoblastic leukemia received allogeneic dendritic cell vaccination, pulsed with Wilms tumor 1 (WT1) peptide, after her third hematopoietic stem cell transplantation (HSCT). The vaccines were generated from the third HSCT donor, who was her younger sister, age 12 years. The patient received 14 vaccines and had no graft-versus-host disease or systemic adverse effect, aside from grade 2 skin reaction at the injection site. WT1-specific immune responses were detected after vaccination by both WT1-tetramer analysis and enzyme-linked immunosorbent spot assay. This strategy may be safe, tolerable and even feasible for patients with a relapse after HSCT.

Long-term surviving recipients of allogeneic hematopoietic stem cell transplantation (HSCT) often suffer from diabetes mellitus (DM). We sought to identify risk factors for the development of post-transplant DM and impaired glucose tolerance (IGT) in pediatric HSCT patients. Glucose tolerance statuses were evaluated in 22 patients aged 6.3-21.8 years who had received allogeneic HSCT between the ages of 0.8-13.5 years. Five patients were diagnosed as having type 2 DM, and treated with insulin or oral hypoglycemic agents. Five patients were included in the IGT group, and the remaining 12 children were in the normal glucose tolerance (NGT) group. The cumulative incidence of DM plus IGT was 11.6 % at 5 years and 69.3 % at 10 years. None of the patients were obese/overweight and none had a family history of DM. There were no significant differences in serum levels of leptin and adiponectin between the DM + IGT and the NGT groups. An average preprandial glucose levels in the DM + IGT group were significantly higher than those in the NGT group from preparative conditioning to 60 days after HSCT. In multivariate analysis, an age of ≥6 years at the time of HSCT was significantly associated with the development of DM + IGT. Additionally, careful follow-up is necessary, even for NGT patients.

advance online publication, February 25, 2014, Juvenile myelomonocytic leukemia (JMML) is a fatal, mixed myeloproliferative and myelodysplastic disorder occurring in infancy and early childhood. Children with JMML have mutually exclusive genetic abnormalities in granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling pathways, inactivation of the NF1 or mutations in PTPN11, NRAS, KRAS and CBL. A whole-exome sequencing study, performed by Sakaguchi et al.,3 has recently demonstrated that in addition to the high frequency of RAS pathway mutations, mutations in SETBP1 and JAK3 are common recurrent secondary events, and that these events may be involved in tumor progression, and are associated with poor clinical outcomes., Article, LEUKEMIA. 28(7):1545-1548 (2014)

There have been no reports of human herpesvirus-6 (HHV-6) encephalitis treatment based on both HHV-6 DNA load and the antiviral agent's concentration in the cerebrospinal fluid (CSF).A 20-year-old male with a hematological malignancy developed HHV-6 encephalitis 15 days after unrelated cord blood transplantation (UCBT). He had fever, chest pain, memory impairment, and insomnia. His CSF showed no increased cell counts, but the amount of HHV-6 DNA was elevated to 2.0 × 10(6) copies/ìgDNA. Magnetic resonance imaging (MRI) of the head revealed abnormal high-intensity signals in the left limbic system on T2-weighted and diffusion-weighted images. Intravenous administration of ganciclovir (GCV) was initiated at 5 mg/kg every 12 h on day 18, and was continued until day 137. The amount of HHV-6 DNA in the plasma became undetectable on day 25. The HHV-6 load in the CSF decreased to 1.5 × 10(3) copies/ìgDNA on day 32, and reached undetectable levels on day 53. The mean concentration of GCV 1 h after an infusion of 5 mg/kg was 4.12 mg/mL in plasma and 0.7 mg/mL in CSF. The chest pain and insomnia disappeared on days 35 and 47, respectively. Memory defects recovered up to day 85.Serial quantification of HHV-6 DNA in CSF may be useful for successful treatment with GCV in post-transplant HHV-6 encephalitis.

Conventional myeloablative conditioning (MAC) regimens often cause severe regimen-related toxicity (RRT). Furthermore, many patients suffer from poor quality of life in accordance with the increase in long-term survivors. We therefore devised a reduced-toxicity myeloablative conditioning (RTMAC) regimen consisting of 8-Gy total body irradiation (TBI), fludarabine (FLU) and cyclophosphamide (CY) for pediatric hematological malignancies. A retrospective single-center analysis was performed on patients with leukemia or myelodysplastic syndrome (MDS), aged ≤20 years, who had received an 8-Gy TBI/FLU/CY RTMAC regimen followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). Thirty-one patients underwent first allo-HSCT after an RTMAC regimen. The diagnoses were acute lymphoblastic leukemia (n = 11), acute myeloid leukemia (n = 13), MDS (n = 4), juvenile myelomonocytic leukemia (n = 1) and acute leukemias of ambiguous lineage (n = 2). While 3 patients showed early hematological relapse, the remaining 28 patients achieved engraftments. None of the patients developed grade 4 or 5 toxicities during the study period. The 5-year overall survival and relapse-free survival were 80% [95% confidence interval: CI, 61–91%] and 71% [95% CI, 52–84%], respectively. Our RTMAC regimen would be less toxic and offers a high probability of survival for children with hematological malignancies.

In order to develop a new tester strain detecting environmental promutagens and procarcinogens, we introduced two plasmids into Salmonella typhimurium TA1535; one contains the cDNAs of human cytochrome P450 (P450 or CYP) 1A2 and NADPH-P450 reductase and the other (pOA101) a umuC"lacZ fusion gene. The newly developed tester strain, S. typhimurium OY1001/1A2, was found to express P450 at a level of 0.15 nmol/ml in whole cell culture. Membrane fractions, when isolated from this tester strain, contained 0.04 P450 nmol/mg protein and a reductase activity of 170 nmol cytochrome c reduced/min/mg protein and were active in catalyzing CYP1A2-dependent 7-ethoxyresorufin O-deethylation and metabolic activation of heterocyclic aromatic amines to DNA-damaging products in a conventional tester S. typhimurium NM2009 strain, only when NADPH was added as a reducing equivalent. In the OA1002/1A2 strain, heterocyclic aromatic amines (e.g., IQ, MeIQ, and MeIQx) were found to be activated to reactive metabolites that cause induction of umuC gene expression in a dose-dependent manner, without addition of external NADPH. These results indicate that the newly established strain can be of use to detect mutagenic and carcinogenic potencies of environmental chemicals without addition of metabolic activation system.

Micafungin (MCFG) is used for the prophylaxis of invasive fungal disease (IFD) after allogeneic hematopoietic stem cell transplantation (HSCT). However, the safety, efficacy, or optimal dosage/blood levels as prophylaxis is uncertain in pediatric HSCT-patients. We prophylactically administered MCFG at 2 mg/kg once daily to 38 children and adolescents undergoing allogeneic HSCT. During MCFG prophylaxis, infusion reactions or adverse events (grades 2–5) related to MCFG use were not found in all the patients. Thus, MCFG prophylaxis was not discontinued and other antifungal agents were not added except for 2 patients in whom probable or possible IFDs developed (completion rate, 94.7 %). To elucidate the influence of HSCT-related complications/drugs on blood concentration of MCFG, we determined the plasma trough and peak levels in 13 and 10 among 38 patients, respectively. The mean trough and peak levels were 3.04 ± 1.21 μg/mL (569 samples) and 9.63 ± 3.62 μg/mL (44 samples), respectively. The peak levels were moderately correlated to the trough levels (R 2 = 0.466). In a patient, the trough level of MCFG transiently increased up to 10.21 μg/mL during hepatic dysfunction due to acute graft-versus-host disease. The MCFG trough levels strongly correlated with T-Bil value (R 2 = 0.894). There was no relationship between the trough levels of MCFG and the circulating concentrations of tacrolimus (R 2 = 0.040). Additionally, MCFG levels were not influenced by treatment with cyclophosphamide or corticosteroids. Prophylaxis with MCFG at 2 mg/kg once daily may be safe, tolerable, and feasible in pediatric HSCT-patients.

No standard treatment has been established in childhood blastic plasmacytoid dendritic cell neoplasma (BPDCN) because of its rarity. We treated with acute lymphoblastic leukemia-type regimen for a child with BPDCN with skin and leukemic involvement. She has been disease-free for 4 years after allogeneic bone marrow transplantation in first complete remission. In 33 cases of pediatric BPDCN, the over survival was significantly lower in the patients with skin manifestation than those without cutaneous involvement. Accordingly, it is important to determine whether allogeneic hematopoietic stem cell transplantation should be applied to first complete remission in the patients with poor prognosis.

Chronic granulomatous disease (CGD) is a rare inherited primary immunodeficiency that affects phagocytic cells. CGD patients are susceptible to fungal infections, especially Aspergillus infections. The management of life-threatening Aspergillus infections in CGD is particularly difficult because some infections cannot be eradicated with standard antifungal treatments and, hence, result in death.A 2-week-old girl developed invasive pulmonary aspergillosis, which rapidly progressed to respiratory failure. Liposomal amphotericin B, micafungin, and voriconazole were not effective. At the age of 2 months, she was diagnosed with p67phox-deficient CGD. In addition to antifungal treatment, the patient received 21 granulocyte transfusions (GTX), which were obtained from 300- or 400-mL whole blood samples from healthy random donors who were not treated with granulocyte-colony-stimulating factor or dexamethasone. The median neutrophil count of the GTX was 1.88 × 10(8) /kg body weight. Rituximab was administered to reduce alloimmunization to human leukocyte antigens (HLA) after the eighth GTX, resulting in their absence of anti-HLA before and after cord blood transplantation (CBT). A marked improvement in her invasive pulmonary aspergillosis was achieved, although the first CBT was rejected. Complete hematopoietic recovery was obtained after the second CBT.Repeated GTX containing relatively low doses of neutrophils might be able to control severe Aspergillus infections in infants with CGD.

Allergic transfusion reactions (ATRs), particularly those caused by plasma-rich platelet concentrates (P-PCs), are an important concern in transfusion medicine. Replacing P-PCs with PCs containing M-sol (M-sol-R-PCs) is expected to prevent ATRs. However, this has not yet been verified by sufficient clinical evidence.A retrospective cohort study was performed between 2008 and 2011. Pediatric patients with hematologic disorders, solid tumors, primary immunodeficiency disorders, or inherited metabolic disorders were transfused with M-sol-R-PCs between 2010 and 2011; the transfusions of P-PCs administered between 2008 and 2011 were compared in terms of frequency and severity of ATRs, corrected count increment (CCI), and occurrence of bleeding. Data were collected for 6 consecutive months on a per-patient basis.Data obtained during 2008 to 2011 showed that of the 78 patients receiving 515 P-PC transfusions, 14 (17.9%) had 17 ATRs (3.3%); 14 and three ATRs were of Grades 1 and 2, respectively. In 2010 to 2011, 49 patients received 620 transfusions of M-sol-R-PCs, and two patients (4.1%) had Grade 1 ATRs (0.3%). Thus, the frequency of ATRs per bag and per patient differed significantly between the two transfusions. No steroid agents were used for the prevention or treatment of ATRs in the M-sol-R-PC group. The CCI (24 hr) for M-sol-R-PCs did not differ from that for P-PCs.M-sol-R-PCs were found to be effective in preventing ATRs without loss of transfusion efficiency in children; however, its efficacy should be further evaluated in prospective clinical trials.

15q24 deletion syndrome is a recently-described chromosomal disorder, characterized by developmental delay, growth deficiency, distinct facial features, digital abnormalities, loose connective tissue, and genital malformations in males. To date, 19 patients have been reported. We report on a 13-year-old boy with this syndrome manifesting childhood myelodysplastic syndrome (MDS). He had characteristic facial features, hypospadias, and mild developmental delay. He showed neutropenia and thrombocytopenia for several years. At age 13 years, bone marrow examination was performed, which showed a sign suggestive of childhood MDS: mild dysplasia in the myeloid, erythroid, and megakaryocytic cell lineages. Array comparative genomic hybridization (array CGH) revealed a de novo 3.4 Mb 15q24.1q24.3 deletion. Although MDS has not been described in patients with the syndrome, a boy was reported to have acute lymphoblastic leukemia (ALL). The development of MDS and hematological malignancy in the syndrome might be caused by the haploinsufficiency of deleted 15q24 segment either alone or in combination with other genetic abnormalities in hematopoietic cells. Further hematological investigation is recommended to be beneficial if physical and hematological examination results are suggestive of hematopoietic disturbance in patients with the syndrome. © 2011 Wiley Periodicals, Inc.

In any epidemiologic study of cardiovascular disease, standardized total serum cholesterol (CH) and triglyceride (TG) measurements are indispensable if different studies are to be compared and secular changes within a group evaluated. In the present study, a lipid standardization program was begun in 1979 under the directions of the Center for Adult Diseases (CAD) in Osaka which had already standardized CH and TG as part of a joint program of the U. S. Center for Disease Control (CDC). After two years, this laboratory was found to meet both precision and accuracy criteria when measuring serum cholesterol and triglyceride using CDC reference values.

A 6.5-year prospective study of cerebral infarction among residents 40 years and older was conducted at the Akadani-Ijimino district in Shibata City, Niigata Prefecture, Japan. The response rate for the initial examination was 85% of 1,182 males and 93% of 1,469 females. Nine hundred and sixty males and 1,339 females who were initially free of stroke were followed up from July 1977 through December 1983. Statistically significant risk factors for cerebral infarction appeared to be age, elevated blood pressure, high R, ST-T changes and atrial fibrillation on ECG, and albuminuria. The ECG abnormalities and albuminuria were due to the high blood pressure persisted over a long period of time. The strength of association of blood pressure with cerebral infarction got weak in comparison with other factors, and funduscopic changes which had been regarded as a risk factor for stroke in 1965-1974 did not reach statistical significance because of the spread of the community-based hypertension control. Even in 1977-1983 when Japanese dietary habits were westernized, neither hyperlipidemia nor obesity appeared to be related to the development of cerebral infarction.