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- Severe Fever with Thrombocytopenia Syndrome Virus, South Korea, 2013. [JOURNAL ARTICLE]
- Emerg Infect Dis 2014 Nov; 20(11):1880-1882.
During 2013, severe fever with thrombocytopenia syndrome was diagnosed in 35 persons in South Korea. Environmental temperature probably affected the monthly and regional distribution of case-patients within the country. Phylogenetic analysis indicated that the isolates from Korea were closely related to isolates from China and Japan.
- Geriatric Fever Score: A New Decision Rule for Geriatric Care. [JOURNAL ARTICLE]
- PLoS One 2014; 9(10):e110927.
Evaluating geriatric patients with fever is time-consuming and challenging. We investigated independent mortality predictors of geriatric patients with fever and developed a prediction rule for emergency care, critical care, and geriatric care physicians to classify patients into mortality risk and disposition groups.Consecutive geriatric patients (≥65 years old) visiting the emergency department (ED) of a university-affiliated medical center between June 1 and July 21, 2010, were enrolled when they met the criteria of fever: a tympanic temperature ≥37.2°C or a baseline temperature elevated ≥1.3°C. Thirty-day mortality was the primary endpoint. Internal validation with bootstrap re-sampling was done.Three hundred thirty geriatric patients were enrolled. We found three independent mortality predictors: Leukocytosis (WBC >12,000 cells/mm3), Severe coma (GCS ≤ 8), and Thrombocytopenia (platelets <150 103/mm3) (LST). After assigning weights to each predictor, we developed a Geriatric Fever Score that stratifies patients into two mortality-risk and disposition groups: low (4.0%) (95% CI: 2.3-6.9%): a general ward or treatment in the ED then discharge and high (30.3%) (95% CI: 17.4-47.3%): consider the intensive care unit. The area under the curve for the rule was 0.73.We found that the Geriatric Fever Score is a simple and rapid rule for predicting 30-day mortality and classifying mortality risk and disposition in geriatric patients with fever, although external validation should be performed to confirm its usefulness in other clinical settings. It might help preserve medical resources for patients in greater need.
- Genetic variation in platinating agent and taxane pathway genes as predictors of outcome and toxicity in advanced non-small-cell lung cancer. [JOURNAL ARTICLE]
- Pharmacogenomics 2014 Sep; 15(12):1565-1574.
Aim: Lung carcinoma is the most common malignancy and the leading cause of cancer deaths worldwide. Although clinical factors including age, performance status and stage influence the likelihood of benefit from and tolerability of chemotherapy, the genetic profile of individual patients may be an independent predictor of response and toxicity. The present study aimed to identify pharmacogenetic markers associated with clinical response and toxicity in patients with advanced non-small cell lung cancer (NSCLC) treated primarily with carboplatin and paclitaxel. Materials & methods: Genomic DNA samples from 90 adult male patients diagnosed with stage IIIB/IV NSCLC were genotyped for SNPs in candidate genes of relevance to platinating agents and paclitaxel and analyzed for association with survival and toxicities in univariate and multivariate models. Results: After adjusting for performance status and stage, SNPs in the drug transporters ABCB1 and ABCC1, as well as within NQO1 were associated with progression-free survival. With respect to hematological and nonhematological toxicities, SNPs in drug transporters (ABCB1 and ABCG2) were associated with thrombocytopenia, nausea and neutropenia, whereas SNPs in the DNA repair pathway genes ERCC4 and XPC were significantly associated with neutropenia and sensory neuropathy, respectively. Conclusion: Our study evaluated and identified SNPs in key candidate genes in platinating agent and taxane pathways associated with outcome and toxicity in advanced NSCLC. If validated in large prospective studies, these findings might provide opportunities to personalize therapeutic strategies. Original submitted 7 April 2014; Revision submitted 11 July 2014.
- Comprehensive Molecular Detection of Tick-Borne Phleboviruses Leads to the Retrospective Identification of Taxonomically Unassigned Bunyaviruses and the Discovery of a Novel Member of the Genus Phlebovirus. [JOURNAL ARTICLE]
- J Virol 2014 Oct 22.
Until the recent emergence of two human pathogenic tick-borne phleboviruses (TBPVs) (Severe Fever with Thrombocytopenia Syndrome virus (SFTSV), and Heartland virus), TBPVs have been neglected as causative agents of human disease. In particular, no studies have addressed the global distribution of TBPVs and consequently, our understanding of the mechanism(s) underlying their evolution and emergence remains poor. In order to provide a useful tool for the ecological and epidemiological study of TBPVs, we have established a simple system that can detect all known TBPVs, based on conventional RT-PCR with degenerate primer sets targeting conserved regions of the viral L genome segment. Using this system, we have determined that several viruses that had been isolated from ticks decades ago but had not been taxonomically identified, are novel TBPVs. Full-genome sequencing of these viruses revealed a novel fourth TBPV cluster distinct from the three known TBPV clusters (i.e. the SFTS, Bhanja, and Uukuniemi groups) and from the mosquito/sandfly-borne phleboviruses. Furthermore, by using tick samples collected in Zambia, we confirmed that our system had enough sensitivity to detect a new TBPV in a single tick homogenate. This virus, tentatively designated as Shibuyunji virus after the region of tick collection, grouped into a novel fourth TBPV cluster. These results indicate that our system can be used as a first-line screening approach for TBPVs and that this kind of work will undoubtedly lead to the discovery of additional novel tick viruses and will expand our knowledge of the evolution and epidemiology of TBPVs.Tick-borne phleboviruses (TBPVs) have been largely neglected until the recent emergence of two virulent viruses, Severe Fever with Thrombocytopenia Syndrome virus and Heartland virus. Little is known about the global distribution of TBPVs or how these viruses evolved and emerged. A major hurdle to study the distribution of TBPVs is the lack of tools to detect these genetically divergent phleboviruses. In order to address this issue, we have developed a simple, rapid, and cheap RT-PCR system that can detect all known TBPVs and which led to the identification of several novel phleboviruses from previously uncharacterized tick-associated virus isolates. Our system can detect virus in a single tick sample as well as novel TBPVs that are genetically distinct from any of the known TBPVs. These results indicate that our system described will be a useful tool for the surveillance of TBPVs and will facilitate understanding of the ecology of TBPVs.
- Implications of cytogenetics for venous thromboembolism in acute myeloid leukaemia. [JOURNAL ARTICLE]
- Thromb Haemost 2014 Oct 23; 113(1)
Due to the high risk of thrombocytopenia and haemorrhage, thrombotic complications have received little attention in patients with acute myeloid leukemia (AML). Furthermore, the predictive role of cytogenetics on venous thromboembolism (VTE) has largely been ignored. This study aimed to evaluate the incidence, risk factors, and prognostic aspects of VTE in AML. A total of 811 consecutive patients with AML were enrolled and analysed retrospectively. Cox time-dependent covariate regression analysis was used to identify the significant predictors of VTE development. To minimise potential confounding factors, we used propensity-score matching to compare overall survival between patients with and without VTE. The six-month and one-year cumulative incidences of VTE were 3.1 % (95 % confidence interval [CI], 2.0-4.7) and 3.9 % (95 % CI, 2.6-5.7), respectively. Of the 26 cases of VTE, 22 (85 %) developed within 6 months of leukemia diagnosis and 13 (50 %) were catheter-related. In multivariate analysis, advanced age (≥ 65 years) (hazard ratio [HR], 2.70; p = 0.03) and increasing cytogenetic risk (common HR, 1.84; p = 0.05) were independent predictors of VTE. There was no significant association between VTE development and decreased survival (p = 0.32 for matched analysis). Advanced age and increasing cytogenetic risk, well-known predictors for clinical outcome in AML, were also independent risk factors of VTE development. Our results suggest that VTE does not hold prognostic implications for AML.
- Systematic Analysis of Pemetrexed-based Chemoradiotherapy for Patients with Locally Advanced or Metastatic Esophageal Cancer. [Journal Article]
- Asian Pac J Cancer Prev 2014; 15(19):8475-8.
This systematic analysis was conducted to evaluate the efficacy and safety of pemetrexed-based chemoradiotherapy in treating patients with locally advanced or metastatic esophageal cancer.Clinical studies evaluating the efficacy and safety of pemetrexed based regimens on response and safety for relevant patients were identified using a predefined search strategy. Pooled response rates (RRs) were calculated.For pemetrexed-based regimens, 4 clinical studies including 47 patients with locally advanced or metastatic esophageal cancer were considered eligible for inclusion. Systematic analysis showed that, in all patients, the pooled RR was 51% (24/47) . Major adverse effects of grade III/IV were esophagitis, neutropenia, thrombocytopenia, anemia anorexia, fatigue, diarrhea, dysphagia and vomiting. No treatment related death occurred with pemetrexed-based treatment.This systematic analysis suggests that pemetrexed based radiotherapy is associated with reasonable activity and good tolerability in treating patients with locally advanced or metastatic esophageal cancer.
- Comprehensive analysis of temozolomide treatment for patients with glioma. [Journal Article]
- Asian Pac J Cancer Prev 2014; 15(19):8405-8.
This analysis was conducted to evaluate the efficacy and safety of temozolomide based chemotherapy in treating patients with glioma.Clinical studies evaluating the efficacy and safety of temozolomide based regimens for patients with glioma were identified using a predefined search strategy. Pooled response rates (RRs) were calculated.In temozolomide based regimens, 5 clinical studies including 152 patients with advanced glioma were considered eligible for inclusion. Four clinical studies included temozolomide. Systematic analysis suggested that, in all patients, pooled CR was 21% (32/152) , and PR was 21% (32/152). Grade 3/4 toxicity included neutropenia, thrombocytopenia, and anemia. No grade 3 or 4 renal or liver toxicity was observed. No treatment related death occurred with temozolomide based treatment.This systematic analysis suggests that temozolomide based regimens are associated with mild response rate and acceptable toxicity for treatment of glioma patients.
- [Experimental Analysis and Countermeasures for EDTA-dependent Pseudothrombocytopenia]. [English Abstract, Journal Article]
- Zhongguo Shi Yan Xue Ye Xue Za Zhi 2014 Sep; 22(5):1345-7.
The purpose of this study was to investigate the incidence of clinically common EDTA-dependent pseudo-thrombocytopenia (EDTA-PTCP) and methols for treating this diseese. A total of 1326 cases of thrombocytopenia found at blood routine examination were amalyzed anong 71 535 patients hospitalized in our hospital from January 2010 to May 2013, and 87 cases of PTCP caused EDTA-K anticoagulant were analyzed again by using sodium citrate auticoagulant, at the same time the platelet formation distribution was observed by microscopy of smear with Wright-Giemsa staining. The results showed that the platelet count detected by using EDTA-K anticoagulant in 87 cases was (56 ± 27)×10(9)/L, while the platelet count detected by using sodium citrate was (185 ± 39)×10(9)/L (t = 1.83,P < 0.01). The pseudo-thrombocytopenia incidence cansed by EDTA-K was 0.12%, it was 6.56% for the total number of thrombocytopenia. It is concluded that the incidence of PTCP cansed by EDTA-K is 0.12%, the PTCP is easily misdiagnosed. Therefore, the specimens of platelet count <100 10(9)/L should be tested again. When the platelet aggregation is found, the specimens should be examined again by using sodium citrate in order to avoid misdiagnosis.
- Autoimmune neutropenia preceding Helicobacter pylori-negative MALT lymphoma with nodal dissemination. [Journal Article]
- Int J Clin Exp Pathol 2014; 7(9):6386-90.
Autoimmune neutropenia (AIN), resulting from granulocyte-specific autoantibodies, is much less frequent than other autoimmune hematologic disorders including autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). These autoimmune disorders may precede, synchronize, or follow collagen disorders, viral infections, and lymphoid neoplasms. Herein we present the first case of AIN in association with Helicobacter pylori-negative mucosa-associated lymphoid tissue (MALT) lymphoma with nodal dissemination. In our case, AIN, accompanied by ITP, occurred prior to the clinical manifestation of lymphoma. AIN and ITP were well managed afterwards, but they relapsed in accordance with the recurrence of lymphoma. The administration of prednisolone at 0.5 mg/kg daily alleviated the cytopenias within a week. In general, combination chemotherapy is performed for the treatment of lymphoma-associated autoimmune hematologic disorders and indeed seems to be effective. Our case indicates that corticosteroid monotherapy may be effective for lymphoma-associated AIN especially when AIN precedes the onset of lymphoma.
- Predictors and outcomes of suspected heparin-induced thrombocytopenia in subarachnoid hemorrhage patients. [Journal Article]
- Interv Neurol 2014 Aug; 2(4):160-8.
Heparin-induced thrombocytopenia (HIT) is a dreaded complication of heparin-related products and correlates with a worse outcome in aneurysmal subarachnoid hemorrhage (SAH) patients.To study the risk factors and outcomes of SAH patients suspected of having HIT, confirmed as present or absent by the platelet factor 4 (PF4) antibody test.All patients with presumed aneurysmal, nontraumatic SAH and having undergone a PF4 test were identified through our research patient database. Charts, laboratory values and images were analyzed retrospectively.We identified 166 patients with SAH who were tested for HIT; 42 patients (25%) had a positive antibody test. There was no difference in platelet profiles or mean platelet nadirs of HIT+ and HIT- patients (147 ± 93 vs. 153 ± 86 ×10(9)/l, respectively). Univariate analysis identified gender, magnesium prophylaxis, Fisher group 3, clipping versus coiling, presence of angiographic vasospasm, number of vasospasm treatments, and day of HIT testing as potential risk factors associated with HIT. A multivariate analysis indicated that female gender (OR 8.2, 95% CI 2.0-33.2), greater number of vasospasm treatments (OR 1.5, 95% CI 1.2-2.0), later day of HIT testing (OR 1.2, 95% CI 1.1-1.3), and clipping (OR 5.0, 95% CI 1.42-10.0) were independently associated with HIT positivity. HIT+ patients showed more infarcts on CT, longer ICU and hospital stays and worse modified Rankin Scale scores on discharge.The presence of HIT in SAH has adverse consequences and is more likely in female patients who have undergone aneurysm clipping and require multiple endovascular vasospasm treatments.