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- Characterization of Severe Fever with Thrombocytopenia Syndrome in Rural Regions of Zhejiang, China. [JOURNAL ARTICLE]
- PLoS One 2014; 9(10):e111127.
Severe fever with thrombocytopenia syndrome virus (SFTSV) infections have recently been found in rural regions of Zhejiang. A severe fever with thrombocytopenia syndrome (SFTS) surveillance and sero-epidemiological investigation was conducted in the districts with outbreaks. During the study period of 2011-2014, a total of 51 SFTSV infection cases were identified and the case fatality rate was 12% (6/51). Ninety two percent of the patients (47/51) were over 50 years of age, and 63% (32/51) of laboratory confirmed cases occurred from May to July. Nine percent (11/120) of the serum samples from local healthy people without symptoms were found to be positive for antibodies to the SFTS virus. SFTSV strains were isolated by culture using Vero, and the whole genomic sequences of two SFTSV strains (01 and Zhao) were sequenced and submitted to the GenBank. Homology analysis showed that the similarity of the target nucleocapsid gene from the SFTSV strains from different geographic areas was 94.2-100%. From the constructed phylogenetic tree, it was found that all the SFTSV strains diverged into two main clusters. Only the SFTSV strains from the Zhejiang (Daishan) region of China and the Yamaguchi, Miyazakj regions of Japan, were clustered into lineage II, consistent with both of these regions being isolated areas with similar geographic features. Two out of eight predicted linear B cell epitopes from the nucleocapsid protein showed mutations between the SFTSV strains of different clusters, but did not contribute to the binding ability of the specific SFTSV antibodies. This study confirmed that SFTSV has been circulating naturally and can cause a seasonal prevalence in Daishan, China. The results also suggest that the molecular characteristics of SFTSV are associated with the geographic region and all SFTSV strains can be divided into two genotypes.
- Evaluation of the immature platelet fraction as an indicator of platelet recovery in dengue patients. [Journal Article]
- Int J Lab Hematol 2014 Oct; 36(5):499-504.
Thrombocytopenia is a common complication in many disorders (such as aplastic anemia, ITP, dengue fever,), the etiology being multifactorial. Immature platelet fraction (IPF) is a new parameter which is a measure of reticulated platelets that reflects the rate of thrombopoiesis. We tried to evaluate IPF as an indicator to predict the recovery of platelets in patients with dengue.A total of 32 patients suffering from dengue fever (as confirmed by NS1 antigen or IgM antibody positivity for dengue) were taken for the study. The platelet count and IPF value of all these patients were evaluated on a daily basis.It was found out that IPF has a strong correlation with the recovery of platelet counts in patients with dengue. 84.3% patients showed recovery within 24 h after attaining the peak IPF, 93.75% of the patients showed recovery within 24-48 h of the rise of the IPF compared with the previous day's value, and 100% patients showed a recovery within 24 h of the fall of the IPF compared with the previous days. It was also observed that 93.75% of the patients show platelet recovery within 24-48 h if the IPF was more than 10%.Based on our study, we concluded that IPF can be used to evaluate the recovery of platelets in patients with dengue. It holds a great promise of becoming a reliable future guide for decisions concerning platelet transfusions.
- A Phase I study of veliparib (ABT-888) in combination with low-dose fractionated whole abdominal radiation therapy in patients with advanced solid malignancies and peritoneal carcinomatosis. [JOURNAL ARTICLE]
- Clin Cancer Res 2014 Oct 29.
Background: Combined low-dose radiation therapy with poly (ADP-ribose) polymerase (PARP) inhibition has been shown to enhance anti-tumor efficacy through potentiating DNA damage. We combined low-dose fractionated whole abdominal radiation (LDFWAR) with escalating doses of veliparib (ABT-888),a small molecule PARP inhibitor, in patients with peritoneal carcinomatosis from advanced solid tumors. Methods: Patients were treated with veliparib (80mg-320mg daily) for a total of 3 cycles. LDFWAR consisted of 21.6 Gy in 36 fractions, 0.6 Gy twice daily on days 1 and 5 for weeks 1-3 of each cycle. Circulating tumor cells (CTCs) were collected and evaluated for ɣ-H2AX. Quality of life (QoL) was assessed using the EORTC-QLQ-C30 questionnaire. Results: Twenty-two patients were treated. Treatment-related grade 3/4 toxicites included lymphopenia (68%), anemia (9%), thrombocytopenia (14%), neutropenia (4%), leukopenia (9%), ascites (4%), vomiting (4%) and dyspnea (4%). No objective responses were observed. Disease stabilization (≥24 wks) was observed in 7 patients (33%). Median PFS was 4.47 months and mOS was 13.04 months. In the subset of 8 ovarian and fallopian cancers (OV), mPFS was 6.77 months and mOS was 17.54 months compared to mPFS 2.71 months and mOS 13.01 months in others. Patients with OV had better QoL over time than those with other cancers. An increased percentage of ɣ-H2AX-positive CTCs was observed in a subset of patients (3/6 with >2 CTCs at baseline). Conclusions: Combined veliparib and LDFWAR is a well-tolerated regimen that resulted in prolonged disease stability for some patients with advanced solid tumors and carcinomatosis, particularly in the OV subpopulation.
- A phase 1/1b study of combined rituximab, bendamustine, and ibrutinib in patients with previously untreated and relapsed/refractory non-Hodgkin's lymphoma. [JOURNAL ARTICLE]
- Blood 2014 Oct 29.
Ibrutinib has single agent activity of 22-68% in relapsed B-cell non-Hodgkin's lymphoma (NHL). This study evaluated the safety and efficacy of ibrutinib combined with rituximab (R) and bendamustine. Patients received R 375 mg/m(2) day 1, bendamustine 90 mg/m(2) days 1 and 2, and ibrutinib (280 or 560 mg) days 1-28 every 28 days for 6 cycles followed by ibrutinib alone until progression. Forty-eight patients enrolled, including 12 patients with follicular lymphoma (FL), 16 with diffuse large cell lymphoma (DLCL), and 17 with mantle cell lymphoma (MCL). No dose limiting toxicities were observed. Patients received a median of 8 cycles, with 26 completing 6 cycles and continuing ibrutinib alone in cycles 7-34. The overall response rate (ORR) was 72%, with 52% complete responses (CR). By histology, the ORR was 94% (76% CR) in MCL, 37% (31% CR) in DLCL, and 90% (50% CR) in FL. Grade 3-4 toxicities included lymphopenia (77%), neutropenia (33%), thrombocytopenia (19%), and rash (25%). Median progression-free survival has not been reached (95% CI, 8.7 months - not reached). The recommended phase 2 dose of ibrutinib in combination with R-bendamustine in patients with NHL is 560 mg. The combination has promising efficacy, particularly in MCL and FL.
- Intravenous immunoglobulin-associated thrombosis: is it such a rare event? Report of a pediatric case and of the Quebec Hemovigilance System. [JOURNAL ARTICLE]
- Transfusion 2014 Oct 29.
Intravenous immunoglobulin (IVIG) is frequently given in autoimmune disorders. Side effects are usually mild but severe complications such as thrombosis may occur. After one patient with IVIG-associated thrombotic complication at Sainte-Justine Hospital, the incidence of serious adverse events (SAEs) reported to the Quebec Hemovigilance System (QHS) was reviewed.This study was a retrospective review of QHS database of IVIG-related thrombotic complications since 2003, including a case report of a pediatric patient.QHS is one of the rare national hemovigilance systems that have included IVIG reports for almost a decade. Over an extended period of 11 years (2003-2013), there have been eight cases of IVIG-related thrombosis, seven in adults and one in the pediatric population (respective rate of 0.06 case and 0.17 case per 100,000 g of IVIG given). The single pediatric case occurred in a 16-year-old female receiving IVIG for severe immune thrombocytopenia.Thrombosis after IVIG is a rare though SAE occurring mostly in adults. This underlines the importance of properly reporting IVIG SAEs to improve hemovigilance data and study such rare events.
- Linezolid versus vancomycin for the treatment of suspected methicillin-resistant Staphylococcus aureus nosocomial pneumonia: a systematic review employing meta-analysis. [JOURNAL ARTICLE]
- Eur J Clin Pharmacol 2014 Oct 30.
The optimal therapy involving linezolid or vancomycin for suspected methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia (NP) remains controversial. This study compared the efficacy and safety of linezolid and vancomycin therapies in patients with NP.A systematic review of randomized controlled trials with meta-analyses performed by searching PubMed, EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials. We screened for relevant randomized controlled studies in which patients with NP were enrolled and linezolid and vancomycin therapies were compared.Nine trials involving 2618 pneumonia patients were reviewed. Linezolid was not found to be superior to vancomycin for clinical cure when categories of pathogen were not considered and in a subgroup of NP patients with MRSA infection [relative risk (RR) = 1.16, 95 % confidence interval (CI) = 0.95-1.43, P = 0.15]. Compared with vancomycin, linezolid has no difference in the overall microbiological eradication rate (RR = 1.12, 95 % CI = 0.96-1.30, P = 0.15) and specific MRSA eradication rate (RR = 1.16, 95 % CI = 0.93-1.45, P = 0.19) in NP patients. In addition, nephrotoxicity was more frequent with vancomycin (RR = 0.50, 95 % CI = 0.31-0.81, P = 0.005), but no differences between the treatments were found for all-cause mortality, thrombocytopenia, gastrointestinal effects, and drug discontinuation due to adverse events.These results suggest that linezolid is not superior to vancomycin with respect to both clinical and microbiological cure rates in patients with MRSA NP.
- Profound autoimmune hemolysis and Evans syndrome in two asplenic patients with babesiosis. [JOURNAL ARTICLE]
- Transfusion 2014 Oct 29.
Evans syndrome (ES) is characterized by the simultaneous or sequential presence of multiple autoimmune cytopenias. It is often secondary to rheumatologic disorders or lymphoid malignancies, but has not previously been associated with babesiosis. Here we present two cases of severe cytopenias in asplenic patients precipitated by active babesiosis.The first patient had a history of Hodgkin's lymphoma in remission and autoimmune hemolytic anemia (AIHA) treated by splenectomy 12 years prior who presented with severe AIHA and thrombocytopenia after Babesia infection. The second patient had a history of ES requiring splenectomy, which relapsed after Babesia infection.The complex presentation and medical histories of both patients made the diagnosis challenging. Both patients' cytopenias responded to therapy, although the use of immunosuppressive agents in patients with active hematologic infections was challenging and required a multidisciplinary approach.These two cases illustrate the possibility of babesiosis to not only reactivate ES in asplenic patients, but also precipitate increased levels of immune deregulation, potentially provoking ES, a phenomenon not previously reported.
- Outcomes Treating Stage Iii Non-Small Cell Lung Carcinoma with Curative-Intent Radiotherapy and Concurrent Carboplatin-Paclitaxel Chemotherapy. [JOURNAL ARTICLE]
- Clin Respir J 2014 Oct 29.
Thoracic radiotherapy administered concurrently with chemotherapy is the standard of care for patients with inoperable stage III non-small cell lung cancer but the optimal chemotherapy regimen is not clearly established. The objective of this study was to assess outcomes in a large cohort of patients treated with curative-intent using carboplatin and paclitaxel.Consecutive patients undergoing curative-intent radiotherapy to 60-66 Gy in 30-33 daily fractions with concurrent weekly carboplatin (AUC=2) and paclitaxel (45mg/m(2) /week) between March 2004 and May 2012 were identified from a prospective database and reviewed individually. A minimum follow-up of three months was required unless death occurred sooner. Response to treatment was defined according to established guidelines on re-staging computed tomography scan at three months. Toxicities were assessed using a standardised scoring system.One hundred and seven patients were analysed. The median follow-up was 43.5 months. Three months after treatment, a complete or partial response was observed in 72 patients (68%) and nine patients (8%) had already died. The overall locoregional failure rate was 47% and failure eventually occurred at any site in 75 patients (70%). Median progression free survival and median survival were 15 and 22 months, respectively. Grade 3-4 neutropaenia, thrombocytopaenia, nephrotoxicity, oesophagitis and pneumonitis were observed in 15%, 1%, 3%, 11% and 9% of patients during treatment, respectively. There was 1 episode of fatal radiation pneumonitis.Treatment with thoracic radiotherapy and concurrent carboplatin and paclitaxel chemotherapy is feasible. Survival and toxicity outcomes compare favorably to those reported using cisplatin-based regimens.
- Inhibition of FcγR-mediated phagocytosis by IVIg is independent of IgG-Fc sialylation and FcγRIIb in human macrophages. [JOURNAL ARTICLE]
- Blood 2014 Oct 28.
In immune thrombocytopenia (ITP) and warm autoimmune hemolytic anemia (wAIHA), circulating IgG-opsonized blood cells are cleared from the circulation by macrophages. Administration of intravenous immunoglobulin (IVIg) can prevent uptake, but the exact working mechanism is not known. The prevailing theory from murine studies, which states that Fc-sialylated IgG alters the balance between activating and inhibitory Fc-gamma receptors (FcγRs) by inducing upregulation of the inhibitory FcγRIIb on effector macrophages, is currently debated. We studied phagocytosis of IgG-opsonized blood cells in a human system, assessing the effect of IVIg and blocking anti-FcγR F(ab')2 fragments on uptake by monocyte-derived macrophages (both M1 and M2 macrophages). Phagocytosis was remarkably sensitive to administration of IVIg but unexpectedly, recombinant Fc-sialylated IgG or sialic acid-enriched IVIg were equally active as unsialylated IgG fractions in mediating this inhibition - independent of FcγRIIb expression. Instead, IVIg inhibited phagocytosis by direct blockade of FcγRs. IgG fractions enriched for IgG-dimers with enhanced avidity for FcγRs showed increased inhibition compared to monomeric IgG fractions. Together, our data demonstrate that inhibition of IgG-mediated phagocytosis in human macrophages by IVIg is dependent on the capacity to directly bind FcγRs but independent of FcγRIIb or sialylation of the Fc fragment in the human setting.
- Hemostatic analysis of dogs naturally envenomed by the African puffadder (Bitis arietans) and snouted cobra (Naja annulifera). [JOURNAL ARTICLE]
- J Vet Emerg Crit Care (San Antonio) 2014 Oct 28.
To investigate hemostatic changes in dogs envenomed by cytotoxic (African puffadder) and neurotoxic snakes (snouted cobra) using thromboelastography (TEG) and plasma-based coagulation assays.Prospective observational clinical study.University teaching hospital.Eighteen client-owned dogs; 9 envenomed by African puffadder (Bitis arietans) and 9 by snouted cobra (Naja annulifera). Ten healthy dogs served as controls.None.Blood was collected at presentation and 24 hours post envenomation. Platelet count, TEG, prothrombin time, activated partial thromboplastin time (aPTT), antithrombin activity, and fibrinogen (Fib) and C-reactive protein (CRP) concentrations were measured. Outcomes were analyzed using linear mixed models at 5% significance. At presentation, R time was significantly prolonged in the puffadder group compared to the cobra (P = 0.01) and control groups (P = 0.05). Platelet count was significantly lower in the puffadder compared to the cobra (P = 0.04) and control groups (P = 0.001), respectively. Antithrombin activity was significantly decreased in the puffadder (P = 0.002) and cobra groups (P = 0.004) compared to the control group. Both prothrombin time and activated partial thromboplastin time were significantly prolonged in the cobra group compared to the control group (P = 0.03 for both). The TEG variables, maximum amplitude (MA) and G, were significantly increased 24 hours post envenomation in the puffadder group compared to their values at presentation (P = 0.05 for both). Fib and CRP concentrations were significantly increased 24 hours post envenomation in both snake-envenomed groups.Prolonged clot initiation was a common feature in puffadder-envenomed dogs at presentation and this was likely venom induced. Snouted cobra-envenomed dogs were normo- to hypercoagulable at presentation. Dogs from both puffadder and cobra groups progressed to a more hypercoagulable by 24 hours post envenomation, most likely due to marked inflammation as indicated by the increased Fib and CRP concentrations. TEG proved a sensitive tool for detecting abnormal hemostasis in snake-envenomed dogs.