Wide spread of Tn2006 in an AbaR4-type resistance island among carbapenem-resistant Acinetobacter baumannii clinical isolates in Taiwan.
Carbapenem resistance in Acinetobacter baumannii is a global problem. The purpose of this study was to elucidate current resistance mechanisms of imipenem-resistant A. baumannii (IRAB) in Taiwan and their correlation with patient outcomes. Acinetobacter baumannii clinical isolates from two teaching hospitals in Taiwan were collected in 2009 and were examined by Etest for determination of the minimum inhibitory concentrations (MICs) of imipenem, ceftazidime and ceftriaxone. Primers specific for carbapenemase genes and upstream regions were designed for PCR amplification. Bacterial isolates were genotyped by pulsed-field gel electrophoresis (PFGE). Clinical presentations of patients were analysed retrospectively. Upstream insertion sequence ISAba1 was found in 34 isolates that carried bla(OXA-23), including 28 with transposon Tn2006 (ISAba1-bla(OXA-23)-ISAba1) in an AbaR4-type resistance island and 6 with Tn2008 (ISAba1-bla(OXA-23)), as well as in 8 isolates carrying ISAba1-bla(OXA-51-like). All of these isolates expressed full resistance to imipenem (MIC>32 mg/L). Forty-one different PFGE genotypes were found among 62 isolates. Tn2006 was found in 19 genotypes (46.3%), which is more common than ISAba1-bla(OXA-51-like) (12.2%) (P=0.001). Prior use of carbapenems or extended-spectrum cephalosporins for ≥5 days was the only independent risk factor significantly associated with IRAB infection (odds ratio=361.175). Higher mortality was significantly associated with infection caused by IRAB and ISAba1-bla(OXA-23)-carrying strains compared with infection caused by imipenem-susceptible A. baumannii and ISAba1-bla(OXA-51-like)-carrying strains (P=0.009 and 0.027, respectively). Tn2006 is currently the most common imipenem resistance determinant, which showed a higher ability to spread among A. baumannii and was associated with a higher mortality in IRAB-infected patients.

title: Primary Epstein-Barr virus infection associated with Kikuchi's disease and hemophagocytic lymphohistiocytosis: a case report and review of the literature.
abstract: An association between hemophagocytic lymphohistiocytosis (HLH) and Kikuchi's disease is rarely seen in children. Here, we present the case of a male adolescent (age 16 years and 3 months) who suffered from spiking fever for more than 1 week, and multiple nodules over the neck and bilateral axilla for 2 months. A skin rash also developed over all four limbs, abdomen and face. Laboratory data and skin biopsy gave results compatible with a diagnosis of Kikuchi's disease. Hemophagocytosis in the bone marrow, hyper-triglyceridemia, elevated ferritin, and splenomegaly were also found, fulfilling the criteria for HLH. A recent primary Epstein-Barr virus infection was also diagnosed by serology. The patient ran a relatively benign course. Intravenous immunoglobulins, steroids or etoposide-containing regimens were not used, and his recovery was uneventful. A review of the literature showed that up to February 2009, 11 additional cases of Kikuchi's disease presenting simultaneously with, or mimicking, HLH had been reported. Complete resolution within several weeks, with no recurrence, was seen in all but one patient (a pregnant woman).

title: Imipenem heteroresistance induced by imipenem in multidrug-resistant Acinetobacter baumannii: mechanism and clinical implications.
abstract: Acinetobacter baumannii has emerged as a major pathogen causing nosocomial infections, particularly in critical patients admitted to the Intensive Care Unit. Increasing resistance to carbapenems in A. baumannii has been observed worldwide. Here we report the clinical impact and mechanism of imipenem heteroresistance (imipenem minimum inhibitory concentration of 6-32 μg/mL with the presence of resistant cells inside the inhibition zone of Etest strips or disks) in multidrug-resistant A. baumannii (MDR-AB). To identify risk factors associated with the emergence of imipenem heteroresistance, a retrospective case-control study was undertaken involving cases with subsequent clinical isolates of the same genotype showing loss of imipenem susceptibility and matched controls with isolates belonging to imipenem-susceptible MDR-AB. The molecular mechanism of heteroresistance was examined. From April 2006 to March 2007, 126 consecutive isolates of MDR-AB were identified from 29 patients. Switch from imipenem susceptibility to heteroresistance was more likely to occur in successive MDR-AB derived from patients who had been exposed to imipenem (length of use 10.9 ± 6.5 days for cases vs. 5.3 ± 4.8 days for controls; P=0.02). An insertion sequence (ISAba1) was found in the promoter region of a class C β-lactamase gene (bla(ADC-29)) in most imipenem-heteroresistant MDR-AB isolates. In vitro experiments indicated that imipenem heteroresistance, which was associated with overexpression of bla(ADC-29), could be induced by imipenem. Carbapenem use was the only risk factor identified for the emergence of carbapenem-heteroresistant MDR-AB. Physicians should weigh the benefits and risks of each carbapenem-based treatment in managing carbapenem-susceptible MDR-AB infection.

title: Transforming growth factor-β1 and major depressive disorder with and without attempted suicide: Preliminary study
abstract: A substantial body of evidence indicates that dysregulation of the immune system is associated with suicidal behavior in major depressive disorder (MDD). Transforming growth factor (TGF)-beta1 is believed to be an important factor in regulating inflammatory responses and to have anti-inflammatory effects. We aimed to identify the role of TGF-beta1 on suicidal depression. The TGF-beta1 polymorphisms at codons 10 and 25 were analyzed in 122 suicidal MDD patients, 61 non-suicidal MDD patients, and 120 control subjects and, among them, in vitro TGF-beta1 productions were measured in 48 suicidal MDD patients, 47 non-suicidal MDD patients, and 91 control subjects. There was no genetic polymorphism at codon 25 and three genotypes at codon 10. No significant difference in the distributions of the TGF-beta1 genotypes was found among the three groups. The in vitro TGF-beta1 productions were significantly higher in suicidal MDD patients (844.3+/-329.7 pg/ml) and in non-suicidal MDD patients (853.0+/-439.7 pg/ml) than in controls (683.0+/-397.0 pg/ml) (P=0.01). In vitro TGF-beta1 productions were not significantly different among patients with any of the TGF-beta1 alleles or genotypes. Our findings suggest that in vitro TGF-beta1 productions play an important role on MDD, but we found no associations between TGF-beta1 and suicidal behavior.

title: Rhabdoid Tumor of the Kidney Is a Component of the Rhabdoid Predisposition Syndrome 

abstract: The rhabdoid predisposition syndrome (RPS) is characterized by pedigrees in which two or more individuals carry germline mutations of the hSNF5/INI1 tumor suppressor gene. The tumors associated with the syndrome include atypical teratoid/rhabdoid tumor (AT/RT), choroid plexus carcinoma, medulloblastoma, and extrarenal rhabdoid tumor. Rhabdoid tumor of the kidney (RTK) has not been described as part of the RPS. We report a case of a 7-month-old boy with RTK whose sister had a malignant cerebellar tumor followed by a malignant lung and pleural tumor of childhood with typical rhabdoid histology. Molecular genetic analysis of the RTK and tissue from the pleural tumor revealed in both cases identical nonsense mutations of the hSNF5/INI1 gene on chromosome 22q11.2, where thymidine was substituted for cytosine in base 472. The proband had an identical germline mutation. This is the fifth genetically analyzed RPS pedigree and the first to include an RTK.

title: Controlling hematopoiesis through sumoylation-dependent regulation of a GATA factor.
abstract: GATA factors establish transcriptional networks that control fundamental developmental processes. Whereas the regulator of hematopoiesis GATA-1 is subject to multiple posttranslational modifications, how these modifications influence GATA-1 function at endogenous loci is unknown. We demonstrate that sumoylation of GATA-1 K137 promotes transcriptional activation only at target genes requiring the coregulator Friend of GATA-1 (FOG-1). A mutation of GATA-1 V205G that disrupts FOG-1 binding and K137 mutations yielded similar phenotypes, although sumoylation was FOG-1 independent, and FOG-1 binding did not require sumoylation. Both mutations dysregulated GATA-1 chromatin occupancy at select sites, FOG-1-dependent gene expression, and were rescued by tethering SUMO-1. While FOG-1- and SUMO-1-dependent genes migrated away from the nuclear periphery upon erythroid maturation, FOG-1- and SUMO-1-independent genes persisted at the periphery. These results illustrate a mechanism that controls trans-acting factor function in a locus-specific manner, and differentially regulated members of the target gene ensemble reside in distinct subnuclear compartments.

title: Primary postpartum hemorrhage: outcome of pelvic arterial embolization in 251 patients at a single institution.
abstract: To evaluate the safety and efficacy of pelvic arterial embolization (PAE) for the treatment of primary postpartum hemorrhage (PPH) and to determine the factors associated with clinical outcomes.



This retrospective single-center study was institutional review board approved, and informed consent was waived. Outcomes were analyzed in 251 patients who underwent PAE for primary PPH between January 2000 and February 2011. Mode of delivery, causes of bleeding, detailed laboratory and treatment records, and clinical outcomes were recorded. Clinical success was defined as cessation of bleeding after initial session of PAE without the need for additional PAE or surgery. Univariate and multivariate analyses were performed to determine the factors related to clinical outcomes.



The clinical success rate was 86.5% (217 of 251). Among the 34 failed cases, 12 underwent repeat PAE, 16 underwent additional surgery, and three recovered with conservative management. Overall bleeding control was achieved in 98.0% (246 of 251) of the patients. Overall mortality was 2% (five of 251) after the first (n = 3) or second (n = 1) session of PAE or additional surgery (n = 1). Among the 113 patients with long-term follow-up, 110 (97.3%) maintained a regular menstrual cycle and 11 had successful pregnancies. Univariate analysis showed that cesarean section delivery, disseminated intravascular coagulation (DIC), and massive transfusion of more than 10 red blood cell units were related to failed PAE. Multivariate analysis showed that DIC (odds ratio, 0.36; P = .04) and massive transfusion (odds ratio, 0.10; P < .001) were significantly related to clinical failure.



PAE is safe and effective for managing primary PPH. Patients with DIC and massive transfusion were likely to have poor results after PAE.

title: Serial MR imaging findings of acute hemorrhagic leukoencephalitis: a case report.
abstract: We report a patient with acute hemorrhagic leukoencephalitis with a focus on serial MR imaging findings. Initial MR imaging of a 42-year-old woman revealed a 2.5-cm focal nonhemorrhagic lesion in the left thalamus and internal capsule. Twenty-four days later, fever and altered consciousness developed, and MR imaging showed huge masslike lesions in both frontal lobes, mainly involving the white matter and the genu of the corpus callosum, with massive edematous swelling that contained multifocal small hemorrhages. Most lesions showed high apparent diffusion coefficient value with peripheral small areas of low apparent diffusion coefficient. On follow-up MR imaging obtained 49 days after initial MR imaging, the lesions progressed with increase in extent and development of rim-enhancing necrosis, despite steroid therapy. Following stereotactic biopsy and subsequent high-dose steroid treatment, the patient recovered with some neurologic sequelae. MR imaging obtained at 72 and 126 days revealed residual necrosis and cerebromalacia in the both frontal lobes.