Clarithromycin Susceptibility Testing of Mycobacterium avium Complex Using 2,3-Diphenyl-5-thienyl-(2)-tetrazolium Chloride Microplate Assay with Middlebrook 7H9 Broth

A series of 119 Mycobacterium avium complex isolates were subjected to clarithromycin susceptibility testing using microplates containing 2,3-diphenyl-5-thienyl-(2)-tetrazolium chloride (STC). Among 119 isolates, 114 (95.8%) were susceptible to clarithromycin and 5 were resistant according to the new and the standard method. STC counts the low cost and reduces the number of procedures needed for susceptibility testing

Higher dextrose delivery via TPN related to the development of hyperglycemia in non-diabetic critically ill patients

The beneficial effects of total parenteral nutrition (TPN) in improving the nutritional status of malnourished patients during hospital stays have been well established. However, recent randomized trials and meta-analyses have reported an increased rate of TPN-associated complications and mortality in critically ill patients. The increased risk of complications during TPN therapy has been linked to the development of hyperglycemia, especially during the first few days of TPN therapy. This retrospective study was conducted to determine whether the amount of dextrose from TPN in the 1st week in the intensive care unit (ICU) was related to the development of hyperglycemia and the clinical outcome. We included 88 non-diabetic critically ill patients who stayed in the medical ICU for more than two days. The subjects were 65 ± 16 years old, and the mean APACHE (Acute Physiology and Chronic Health Evaluation) II score upon admission was 20.9 ± 7.1. The subjects received 2.3 ± 1.4 g/kg/day of dextrose intravenously. We divided the subjects into two groups according to the mean blood glucose (BG) level during the 1st week of ICU stay: < 140 mg/dl vs ≥ 140 mg/dl. Baseline BG and the amount of dextrose delivered via TPN were significantly higher in the hyperglycemia group than those in the normoglycemia group. Mortality was higher in the hyperglycemia group than in the normoglycemia group (42.4% vs 12.8%, P = 0.008). The amount of dextrose from TPN was the only significant variable in the multiple linear regression analysis, which included age, APACHE II score, baseline blood glucose concentration and dextrose delivery via TPN as independent variables. We concluded that the amount of dextrose delivered via TPN might be associated with the development of hyperglycemia in critically ill patients without a history of diabetes mellitus. The amount of dextrose in TPN should be decided and adapted carefully to maintain blood glucose within the target range

Micafungin prophylaxis for acute leukemia patients undergoing induction chemotherapy

Background Micafungin is a well-tolerated and effective prophylactic antifungal agent used in hematologic diseases. In this prospective trial, we evaluated the efficacy and safety of prophylactic micafungin during first induction chemotherapy in patients with acute leukemia. We also compared outcomes of prophylactic micafungin with those of prophylactic posaconazole in acute myeloid leukemia (AML). Methods Medically fit patients with newly diagnosed acute leukemia received 50 mg micafungin intravenously once daily from the initiation of first induction chemotherapy to recovery of neutrophil count, suspected fungal infection, or unacceptable drug-related toxicity (Clinicaltrials.gov number, NCT02440178). The primary end point was incidence of invasive fungal infection, and the secondary end points were adverse events of prophylactic micafungin and mortality during induction therapy. Results The 65 patients (median age = 51 years, male:female = 34:31) enrolled in this study had diagnoses of AML (33, 50.8%), acute lymphoblastic leukemia (31, 47.7%), and acute biphenotypic leukemia (1, 1.5%). Median duration of micafungin treatment was 24 days (range 1–68), with proven invasive fungal disease in one patient (1.5%) and possible fungal infection in two patients (3.1%). Three of the patients (4.6%) experienced the following adverse events, but all events were tolerable: liver function abnormality (Grade 2, n = 1; Grade 3, n = 1) and allergic reaction (Grade 2, n = 1). Three patients died during induction therapy, and invasive aspergillosis pneumonia was the cause of death for one of those patients. Overall, 19 patients (29.2%) discontinued prophylactic micafungin, and 18 (27.7%) patients switched to another antifungal agent. We observed no fungal infections caused by amphotericin B-resistant organisms. In AML patients, outcomes of prophylactic micafungin during induction chemotherapy did not differ significantly with those of prophylactic posaconazole with regard to incidence of fungal infections, rate of discontinuation, or safety. Conclusions Our study demonstrates that prophylactic micafungin is safe and effective in patients with acute leukemia undergoing induction chemotherapy. Outcomes in patients with AML were similar to those of prophylactic posaconazole, indicating the usefulness of micafungin as a prophylactic antifungal agent during induction chemotherapy for AML. Trial registration Clinicaltrials.gov NCT02440178, registered May 12th 2015.This study was funded by Astellas Pharma Korea, Inc. Funding source had no role in the study design, data collection, data analysis or data interpretation

A test of the submentalizing hypothesis : apes' performance in a false belief task inanimate control

Financial support came from Ministry of Education, Culture, Sports, Science and Technology (K-CONNEX to FK), Japan Society for Promotion of Science (KAKENHI 26885040, 16K21108 to FK), JSPS (KAKENHI 26245069, 24000001 to SH), and European Research Council (Synergy grant 609819 SOMICS to JC).Much debate concerns whether any nonhuman animals share with humans the ability to infer others' mental states, such as desires and beliefs. In a recent eye-tracking false-belief task, we showed that great apes correctly anticipated that a human actor would search for a goal object where he had last seen it, even though the apes themselves knew that it was no longer there. In response, Heyes proposed that apes' looking behavior was guided not by social cognitive mechanisms but rather domain-general cueing effects, and suggested the use of inanimate controls to test this alternative submentalizing hypothesis. In the present study, we implemented the suggested inanimate control of our previous false-belief task. Apes attended well to key events but showed markedly fewer anticipatory looks and no significant tendency to look to the correct location. We thus found no evidence that submentalizing was responsible for apes' anticipatory looks in our false-belief task.Publisher PDFPeer reviewe

Pre-Engraftment Syndrome after Unrelated Cord Blood Transplantation: A Predictor of Engraftment and Acute Graft-versus-Host Disease

AbstractPre-engraftment syndrome (PES) is poorly characterized, and its clinical significance and the prognostic impact after unrelated cord blood transplantation (CBT) are unclear. To address these issues, we retrospectively analyzed the incidence, risk factors, and clinical outcomes of PES in unrelated CBT recipients. Data of 381 patients who received unrelated CBT from 18 medical centers in Korea were reviewed. PES was defined as unexplained fever >38.3°C not associated with infection, and/or unexplained skin rash with or without evidence of fluid retention before neutrophil recovery. PES developed in 102 patients (26.8%) at a median of 7 days after CBT. Of these patients, 74 patients (72.5%) received intravenous corticosteroid at a median dose of 1 mg/kg/day, and of these, 95% showed clinical improvement. Risk factors for developing PES included low risk disease, myeloablative conditioning, graft-versus-host disease (GVHD) prophylaxis without methotrexate or corticosteroid, and >5.43 x 107/kg infused nucleated cells. Absence of PES was one of the risk factors for graft failure in multivariate analysis. The cumulative incidence of grade II to grade IV acute GVHD by 100 days after CBT was higher in patients with PES than in those without PES (56.0% versus 34.4%, P < .01). PES was not associated with chronic GVHD, treatment-related mortality, relapse, or overall survival. PES seems to be common after CBT and may be associated with enhanced engraftment without significant morbidity

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe