For effective CP infusion in MERS, donor plasma with a neutralization activity of a PRNT titre ≥1:80 should be used. ELISA IgG could substitute for the neutralization test in resource-limited situations.

Key Points We evaluated interference with integrin alpha4–mediated stromal adhesion as a new acute lymphoblastic leukemia treatment. Integrin alpha4 blockade using natalizumab in combination with chemotherapy sensitizes pre-B acute lymphoblastic leukemia to chemotherapy.

Relapse of drug-resistant acute lymphoblastic leukemia (ALL) has been associated with increased expression of survivin/BIRC5, an inhibitor of apoptosis protein, suggesting a survival advantage for ALL cells. In the present study, we report that inhibition of survivin in patientderived ALL can eradicate leukemia.Targeting survivin with shRNA in combination with chemotherapy resulted in no detectable minimal residual disease in a xenograft model of primary ALL. Similarly, pharmacologic knock-down of survivin using EZN-3042, a novel locked nucleic acid antisense oligonucleotide, in combination with chemotherapy elimi- IntroductionWhereas the overall prognosis for patients with acute lymphoblastic leukemia (ALL) has improved over the past decades, with an overall survival of approximately 45%-60% for adults 1 and approximately 80% for children, 2,3 relapse of drug-resistant leukemia remains a significant problem. Although cure rates in children are high, recurrent leukemia leads to death in 50%-95% of cases depending on the site of recurrence. 4 Moreover, survivors often suffer from secondary neoplasms and chronic or late-occurring health problems. 5 Survivin (BIRC5), a member of the inhibitor of apoptosis protein (IAP) gene family, 6 has been shown to inhibit apoptosis, enhance proliferation and promote angiogenesis, 7,8 but an indirect association with pro-and antiapoptotic proteins has also been described. 7,9,10 Caspase-independent inhibition of cell death has been attributed to the inhibition of apoptosis-inducing factordependent apoptotic pathways, which are known to induce caspaseindependent DNA fragmentation. 11 Death of cells lacking survivin is thought to be due to incomplete mitosis. 12 Survivin is localized to the microtubules of the mitotic spindle, where it plays an essential role in maintaining high fidelity at cell-cycle checkpoints and transitions. 13 Survivin is itself up-regulated in a cell-cycledependent manner at the G 2 /M phase. 14 Survivin associates with Aurora B kinase and Borrealin to form the chromosome passenger complex that is involved in mitosis, 15 cell-cycle progression, and cytokinesis. 16 Survivin was also shown to play a role in the proliferation of leukemia that was induced by internal tandem duplication of FLT3, 17 and may promote tumorigenesis in vivo by imparting a survival advantage. 18 Survivin is selectively expressed in fetal and proliferating tissues and in various solid tumors 19 and hematologic malignancies. 20 In addition, elevated survivin expression in cancer has been associated with poor prognosis. In particular, gene-expression analysis of matched diagnosis-relapse pairs of ALL samples revealed higher expression levels of survivin at relapse than at diagnosis. 21 However, whether survivin inhibition can actually prevent relapse in primary ALL has not been examined. In the present study, we investigated the role of survivin in primary ALL and evaluated survivin as a potential target for therapy of primary ALL. Methods Patient samplesBone marrow and peripheral blood...

Middle East respiratory syndrome (MERS) is a lethal respiratory disease — caused by MERS-coronavirus (MERS-CoV) which was first identified in 2012. Especially, pregnant women can be expected as highly vulnerable candidates for this viral infection. In May 2015, this virus was spread in Korea and a pregnant woman was confirmed with positive result of MERS-CoV polymerase chain reaction (PCR). Her condition was improved only with conservative treatment. After a full recovery of MERS, the patient manifested abrupt vaginal bleeding with rupture of membrane. Under an impression of placenta abruption, an emergent cesarean section was performed. Our team performed many laboratory tests related to MERS-CoV and all results were negative. We report the first case of MERS-CoV infection during pregnancy occurred outside of the Middle East. Also, this case showed relatively benign maternal course which resulted in full recovery with subsequent healthy full-term delivery without MERS-CoV transmission.

Cyclin dependent kinase 1 (Cdk1) have previously reported correlation with cancer growth and a key regulator for cell cycle. Mostly, Cdk1′s function of nucleus for cell cycle is well known to be associated with cancer, but cytoplasmic Cdk1′s traits are not clearly identified, yet. We revealed that tissue microarray blocks of epithelial ovarian cancer (n = 249) showed increased level of cytoplasmic Cdk1 (p < 0.001), but not in nucleus (p = 0.192) of histologic cell type independently. On survival analysis, Cdk1 overexpression conferred a significantly worse prognosis in 5-year overall survival (Log-rank p = 0.028, Hazard ratio = 2.016, 95% CI = 1.097 to 4.635). Also, the expression of Cdk1 was increased in ovarian cancer cell lines and Gene Expression Omnibus datasets. When the expression and activity of Cdk1 were inhibited by si-Cdk1 or RO-3306 which is a potent Cdk1 inhibitor, the growth of ovarian cancer was diminished. Moreover, combined treatment with RO-3306 and cisplatin in ovarian cancer significantly elevated anti-cancer effects than single-agent treatment. In conclusion, cytoplasmic Cdk1 expression which was elevated in ovarian cancer predicts a poor overall survival. The inhibition of Cdk1 expression and activity reduced ovarian cancer growth.

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BackgroundA reliable rapid assay for hepatitis C virus (HCV) may be helpful in various clinical settings. We evaluated the performance of the OraQuick HCV Rapid Antibody Test (OraSure Technologies Inc., Bethlehem, PA, USA).MethodsClinical sensitivity and specificity were evaluated with oral fluids and sera from 137 patients diagnosed with hepatitis C and 300 healthy blood donors in a multi-center collaborative study. The stored sera of 200 proven HCV-infected patients and 200 healthy subjects were also evaluated. Analytical sensitivity was estimated with 4 commercial seroconversion panels and 7 Korean reference panels. The performance of 4 laboratory-based tests (3 chemiluminescence assays and 1 enzyme immunoassay) and 4 rapid test kits was compared. We also assessed the interference due to bilirubin, hemoglobin, lipid, rheumatoid factor, multipara, and several viral infections.ResultsThe clinical sensitivity and specificity of the OraQuick HCV test using oral fluid were 97.8% (95% confidence interval [CI], 93.2-99.4%) and 100% (95% CI, 98.4-100%), respectively. The clinical sensitivity using serum samples was 100%. Using the 4 seroconversion panels, the OraQuick HCV test showed results comparable to those of the laboratory-based assays; its analytical sensitivity was higher than that of the other rapid test kits. There was no cross-reactivity with common interfering factors.ConclusionsThe clinical performance of the OraQuick HCV Test is comparable to that of laboratory-based tests with both serum and oral fluid. This supports the supplementary use of rapid HCV testing using oral fluid in various medical and non-medical settings.

The aim of this study was to investigate the impact of the induction treatment with SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, and etoposide) chemotherapy and consolidation with upfront autologous stem cell transplantation (ASCT) on clinical outcomes of patients with stage IV extranodal natural killer/T-cell lymphoma (ENKTL). We analyzed the treatment response to SMILE and toxicity, and explored the feasibility of upfront ASCT in 27 patients with stage IV ENKTL out of patients who were enrolled into our prospective cohort studies. The median age of patients was 45 years (range: 17-65 years), and all patients had disseminated disease. The overall response rate to SMILE induction treatment was 59 % (16/27) including nine complete responses. However, five patients died due to grade IV febrile neutropenia during SMILE and six patients did not respond to SMILE. Eleven patients could undergo ASCT, and there was no transplantation-related mortality. The survival outcome of patients underwent ASCT was better than patients who could not (P < 0.05). However, four patients relapsed even after ASCT, thus, the median overall survival was 10.6 months, and the median progression-free survival was 5.1 months. Pretreatment Epstein-Barr virus (EBV) DNA titer was only independent prognostic factor for overall survival. In conclusion, our results suggest SMILE followed by ASCT might be an effective treatment strategy for stage IV ENKTL. However, considering frequent occurrences of disease relapse and treatment-related mortality, additional efforts are required to improve treatment outcomes of stage IV ENKTL patients.