ResearchPad - thrombocytopenia https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Association between single nucleotide polymorphisms (SNPs) of IL1, IL12, IL28 and TLR4 and symptoms of congenital cytomegalovirus infection]]> https://www.researchpad.co/article/elastic_article_15749 Congenital cytomegalovirus (cCMV) infection is the most common intrauterine infection. A non-specific immune response is the first line of host defense mechanism against human cytomegalovirus (HCMV). There is limited data on associations between Single Nucleotide Polymorphisms (SNPs) in genes involving innate immunity and the risk and clinical manifestation of cCMV infection. The aim of the study was to investigate association between selected SNPs in genes encoding cytokines and cytokine receptors, and predisposition to cCMV infection including symptomatic course of disease and symptoms. A panel of eight SNPs: IL1B rs16944, IL12B rs3212227, IL28B rs12979860, CCL2 rs1024611, DC-SIGN rs735240, TLR2 rs5743708, TLR4 rs4986791, TLR9 rs352140 was analyzed in 233 infants (92 cCMV-infected and 141 healthy controls). Associations between genotyped SNPs and predisposition to cCMV infection and symptoms were analyzed. The association analysis was performed using SNPStats software. No statistically significant association was found between any genotyped SNPs and predisposition to cCMV infection and symptomatic course of disease. In relation to particular symptoms, polymorphism of IL12B rs3212227 was linked to decreased risk of prematurity (OR = 0.37;95%CI,0.14–0.98;p = 0.025), while polymorphism of IL1B rs16944 was linked to reduced risk of splenomegaly (OR = 0.36;95%CI,0.14–0.98; p = 0.034) in infants with cCMV infection. An increased risk of thrombocytopenia was associated with IL28B rs12979860 polymorphism (OR = 2.55;95%CI,1.03–6.32;p = 0.042), while hepatitis was associated with SNP of TLR4rs4986791 (OR = 7.80;95%CI,1.49–40,81; p = 0.024). This is the first study to demonstrate four new associations between SNPs in selected genes (IL1B, IL12B, IL28B, TLR4) and particular symptoms in cCMV disease. Further studies on the role of SNPs in the pathogenesis of cCMV infection and incorporation of selected SNPs in the clinical practice might be considered in the future.

]]>
<![CDATA[Severe Fever with Thrombocytopenia Syndrome, Japan, 2013–2017]]> https://www.researchpad.co/article/Needd9831-b5a5-40f9-a173-e1302c5e8acf

We conducted an epidemiologic study of severe fever with thrombocytopenia syndrome (SFTS) in Japan during 2013–2017. Of 303 cases reported during that period, 133 (44%) were included in this study. The median time between onset of illness and diagnosis of SFTS shortened, from 11.5 to 3.0 days, but the case-fatality rate remained high, at 27%. In 64 patients (48%), a close contact with companion animals was reported within 2 weeks of disease onset. Of these 64 patients, 40 were surveyed further, and we confirmed that 3 had direct contact with body fluids of ill companion animals; 2 had direct contact with the saliva of an ill feral cat or pet dog. These patients reported no history of tick bite, suggesting that ill companion animals might be a source of SFTS virus transmission. Direct contact with the body fluids of ill companion animals should be avoided.

]]>
<![CDATA[Real-life experience of lusutrombopag for cirrhotic patients with low platelet counts being prepared for invasive procedures]]> https://www.researchpad.co/article/5c70675dd5eed0c4847c6f1c

Background and aims

The present study aimed to report our real-life experience of the TPO receptor agonist lusutrombopag for cirrhotic patients with low platelet counts.

Methods

We studied platelet counts in 1,760 cirrhotic patients undergoing invasive procedures at our hospital between January 2014 and December 2017. In addition, we studied 25 patients who were administered lusutrombopag before invasive procedures between June 2017 and January 2018. Effectiveness of lusutrombopag to raise platelet counts and to avoid transfusion and treatment-related adverse events were analyzed.

Results

In 1,760 cirrhotic patients without lusutrombopag prior to invasive procedures, proportion of patients whose platelet counts <50,000/μL and needed platelet transfusions were 66% (n = 27/41) for radiofrequency ablation, 43% (n = 21/49) for transarterial chemoembolization, and 55% (n = 21/38) for endoscopic injection sclerotherapy / endoscopic variceal ligation, respectively. In 25 cirrhotic patients treated by lusutrombopag prior to the invasive procedures, platelet counts significantly increased compared with baseline (82,000 ± 26,000 vs. 41,000 ± 11,000/μL) (p < 0.01). Out of 25 patients, only 4 patients (16%) needed platelet transfusion before the invasive procedures. The proportion of patients with low platelet count and who needed platelet transfusions was significantly low in patients treated with lusutrombopag compared to those not treated with lusutrombopag (16% (4/25) vs. 54% (69/128), p = 0.001). Platelet counts after lusutrombopag treatment and prior to invasive procedures were lower in patients with a baseline platelet count ≤30,000/μL (n = 8) compared with those with a baseline platelet count >30,000/μL (n = 17) (50,000 ± 20,000 vs 86,000 ± 26,000/μL, p = 0.002). Patients with a baseline platelet count ≤30,000/μL with spleen index (calculated by multiplying the transverse diameter by the vertical diameter measured by ultrasonography) ≥40 cm2 (n = 3) had a lower response rate to lusutrombopag compared to those with spleen index <40 cm2 (n = 5) (0% vs. 100%, p = 0.02). Hemorrhagic complication was not observed. Recurrence of portal thrombosis was observed and thrombolysis therapy was required in one patient who had prior history of thrombosis.

Conclusions

Lusutrombopag is an effective and safe drug for thrombocytopenia in cirrhotic patients, and can reduce the frequency of platelet transfusions.

]]>
<![CDATA[Magnitude and associated factors of cytopenias among antiretroviral therapy naïve Human Immunodeficiency Virus infected adults in Dessie, Northeast Ethiopia]]> https://www.researchpad.co/article/5c6dc997d5eed0c484529e80

Background

Hematologic abnormalities involving peripheral blood cell cytopenias are strong predictors of morbidity, mortality and poor antiretroviral therapy (ART) outcomes of HIV infected individuals. However, limited studies are conducted in resource-limited settings of sub-Saharan Africa that have addressed the magnitude and associated factors of cytopenias. This study aimed to investigate the magnitude and associated factors of cytopenias among ART naïve HIV infected adult Ethiopians.

Materials and methods

A cross-sectional study was conducted among ART naïve HIV infected individuals attending at ART unit of Dessie Referral Hospital between November 01, 2015 and April 30, 2016. A total of 402 adults were included using consecutive sampling. Socio-demographic, clinical and laboratory data of patients were collected. The data were entered to Epi Info version 3.4.3 and analyzed using SPSS version 20 software (SPSS INC, Chicago, IL, USA). Factors associated with cytopenias were analyzed first using bivariate and then multivariate logistic regression models. An odds ratio with 95% confidence interval was used to measure the strength of association. For all statistical significant tests, the cut-off value was set at P<0.05.

Results

In this study, the overall magnitude of any cytopenia, anemia, leucopenia and thrombocytopenia were 63.4%, 43.5%, 24.4% and 18.7%, respectively. In multivariate logistic regression analysis, severe immunosuppression and WHO clinical stage IV HIV disease were significantly associated with increased prevalence of cytopenias. In addition, older age and younger age showed significant association with increased prevalence of anemia and leucopenia, respectively.

Conclusion

Frequent occurrence of cytopenias was independently associated with severe immunosuppression and WHO clinical stage IV HIV disease. Further longitudinal multicenter studies are recommended to bolster the findings of this study in order to suggest the need of routine assessment and management of hematological abnormalities for optimal choice of initial antiretroviral agents and prevention of further morbidities.

]]>
<![CDATA[Platelet count abnormalities and peri-operative outcomes in adults undergoing elective, non-cardiac surgery]]> https://www.researchpad.co/article/5c6b2682d5eed0c484289bce

Background

Anemia and transfusion of blood in the peri-operative period have been shown to be associated with increased morbidity and mortality across a wide variety of non-cardiac surgeries. While tests of coagulation, including the platelet count, have frequently been used to identify patients with an increased risk of peri-operative bleeding, results have been equivocal. The aim of this study was to assess the effect of platelet level on outcomes in patients undergoing elective surgery.

Materials and methods

Retrospective cohort analysis of prospectively-collected clinical data from American College of Surgeons National Surgical Quality Improvement Program (NSQIP) between 2006–2016.

Results

We identified 3,884,400 adult patients who underwent elective, non-cardiac surgery from 2006–2016 at hospitals participating in NSQIP, a prospectively-collected, national clinical database with established reproducibility and validity. After controlling for all peri- and intraoperative factors by matching on propensity scores, patients with all levels of thrombocytopenia or thrombocytosis had higher odds for perioperative transfusion. All levels of thrombocytopenia were associated with higher mortality, but there was no association with complications or other morbidity after matching. On the other hand, thrombocytosis was not associated with mortality; but odds for postoperative complications and 30-day return to the operating room remained slightly increased after matching.

Conclusions

These findings may guide surgeons in the appropriate use and appreciation of the utility of pre-operative screening of the platelet count prior to an elective, non-cardiac surgery.

]]>
<![CDATA[Demonstration of background rates of three conditions of interest for vaccine safety surveillance]]> https://www.researchpad.co/article/5c478c70d5eed0c484bd256c

Introduction

Adverse events following immunization (AEFIs) are unwanted or unexpected health outcomes following vaccination, which may or may not be causally-linked to vaccines. AEFI reporting is important to post-marketing vaccine safety surveillance and has the potential to identify new or rare AEFIs, show increases in known AEFIs, and help to maintain public confidence in vaccine programs. Knowledge of the expected incidence (i.e. background rate) of a possible AEFI is essential to the investigation of vaccine safety signals. We selected three rarely reported AEFIs representing the spectrum of causal association with vaccines, from proven (immune thrombocytopenia [ITP]) to questioned (Kawasaki disease [KD]) to unsubstantiated (multiple sclerosis [MS]) and determined their background rates.

Methods

We extracted data on hospitalizations (CIHI Discharge Abstract Database) for ITP, KD, and MS among Ontario children for the period 2005 to 2014 from IntelliHEALTH. As ITP can be managed without hospitalization, we also extracted emergency department (ED) visits from the CIHI National Ambulatory Care Reporting System. For all conditions, we only counted the first visit and if the same child had both an ED visit and a hospitalization for ITP, only the hospitalization was included. We calculated rates by year, age group and sex using population estimates from 2005–2014, focusing on age groups within the Ontario immunization schedule around vaccine(s) of interest.

Results

Per 100,000 population, annual age-specific incidence of ITP in children age 1 to 7 years ranged from 8.9 to 12.2 and annual incidence of KD in children less than 5 years ranged from 19.1 to 32.1. Average annualized incidence of adolescent (11–17 years) MS across the study period was 0.8 per 100,000.

Discussion

Despite limitations, including lack of clinical validation, this study provides an example of how health administrative data can be used to determine background rates which may assist with interpretation of passive vaccine safety surveillance.

]]>
<![CDATA[Iron chelating properties of Eltrombopag: Investigating its role in thalassemia-induced osteoporosis]]> https://www.researchpad.co/article/5c0ed779d5eed0c484f141f9

Chronic blood transfusions are responsible to cause iron overload, which leads to several complications to end organs and osteoporosis. Iron chelation is needed to remove iron excess and to contain bone-mass loss. Deferasirox is the most recent oral iron chelator that prevents transfusion related iron overload complications. Recently Eltrombopag (ELT) iron chelating properties are emerging. ELT is an agonist at Thrombopoietin receptor, used in treatment of thrombocytopenia. We tested ELT and Deferasirox in iron overloaded osteoclasts from thalassemic patients and donors measuring intracellular iron, TRAP expression and osteoclast activity. We confirmed ELT iron chelation capacity also in bone tissue and a synergic effect when used with Deferasirox. Moreover, having demonstrated its effects on osteoclast activity, we suggest for the first time that ELT could ameliorate bone tissue’s health reducing bone mass loss.

]]>
<![CDATA[Hemostatic Dysfunction Is Increased in Patients with Hepatosplenic Schistosomiasis Mansoni and Advanced Periportal Fibrosis]]> https://www.researchpad.co/article/5989daceab0ee8fa60bb51bf

Background

Schistosomiasis mansoni is an endemic parasitic disease and a public health problem in Northeast Brazil. In some patients, hepatic abnormalities lead to periportal fibrosis and result in the most severe clinical form, hepatosplenic schistosomiasis. This study aimed to evaluate whether abnormal blood coagulation and liver function tests in patients with hepatosplenic schistosomiasis (n = 55) correlate with the severity of their periportal fibrosis.

Methodology/Principal Findings

Blood samples were used for liver function tests, hemogram and prothrombin time (International Normalized Ratio, INR). The blood coagulation factors (II, VII, VIII, IX and X), protein C and antithrombin IIa (ATIIa), plasminogen activator inhibitor 1 (PAI-1) and D-dimer were measured by photometry or enzyme linked immunosorbent assay. Hyperfibrinolysis was defined on the basis of PAI-1 levels and a D-dimer concentration greater than a standard cut-off of 483 ng/mL. Standard liver function tests were all abnormal in the patient group compared to healthy controls (n = 29), including raised serum transaminases (p<0.001) and lower levels of albumin (p = 0.0156). Platelet counts were 50% lower in patients, while for coagulation factors there was a 40% increase in the INR (p<0.001) and reduced levels of Factor VII and protein C in patients compared to the controls (both p<0.001). Additionally, patients with more advanced fibrosis (n = 38) had lower levels of protein C compared to those with only central fibrosis (p = 0.0124). The concentration of plasma PAI-1 in patients was one-third that of the control group (p<0.001), and D-dimer levels 2.2 times higher (p<0.001) with 13 of the 55 patients having levels above the cut-off.

Conclusion/Significance

This study confirms that hemostatic abnormalities are associated with reduced liver function and increased liver fibrosis. Of note was the finding that a quarter of patients with hepatosplenic schistosomiasis and advanced periportal fibrosis have hyperfibrinolysis, as judged by excessive levels of D-dimer, which may predispose them to gastrointestinal bleeding.

]]>
<![CDATA[Increased Number of Tc17 and Correlation with Th17 Cells in Patients with Immune Thrombocytopenia]]> https://www.researchpad.co/article/5989da3eab0ee8fa60b89301

Background

IL-17-secreting CD8+ T cells (Tc17 subset) have recently been defined as a subpopulation of effector T cells implicated in the pathogenesis of autoimmune diseases. The role of Tc17 and correlation with Th17 cells in the pathophysiology of immune thrombocytopenia (ITP) remain unsettled.

Design and Methods

We studied 47 ITP patients (20 newly-diagnosed and 27 with complete response) and 34 healthy controls. IL-17-producing CD3+CD8+ cells (Tc17) and IL-17-producing CD3+CD8− cells (Th17) were evaluated by flow cytometry and expressed as a percentage of the total number of CD3+ cells. Specific anti-platelet glycoprotein (GP) GPIIb/IIIa and/or GPIb/IX autoantibodies were measured by modified monoclonal antibody specific immobilization of platelet antigens. Peripheral blood mononuclear cells of ITP patients were isolated, incubated in the presence of 0, 0.25, 0.5, or 1 µmol/L of dexamethasone for 72 h, and collected to detect Tc17 and Th17 cells by flow cytometric analysis.

Results

IL-17 was expressed on CD3+CD8− and CD3+CD8+ T cells. The percentages of Tc17 and Th17 cells in newly-diagnosed patients were significantly elevated compared to controls, and Tc17 was decreased after clinical treatment. The Th17∶Tc17 ratio was significantly lower in newly-diagnosed patients compared with controls, and was increased in patients who had complete response. There was a significantly positive correlation between Tc17 and Th17 cells in the control group, but not in the ITP patients. A positive correlation existed between Tc17 and the CD8∶CD4 ratio, as well as CD8+ cells in patients with ITP. The frequencies of Tc17 were marginally higher in autoantibody-negative patients than autoantibody-positive patients. Moreover, both Tc17 and Th17 cell percentages decreased as the concentration of dexamethasone in the culture media increased in ITP patients.

Conclusions

Tc17 and the Th17 subset are involved in the immunopathology of ITP. Blocking the abnormally increased number of Tc17 may be a reasonable therapeutic strategy for ITP.

]]>
<![CDATA[Severe Fever with Thrombocytopenia Syndrome in South Korea, 2013-2015]]> https://www.researchpad.co/article/5989d9ddab0ee8fa60b68484

Background

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was recently identified in China, South Korea and Japan. The objective of the study was to evaluate the epidemiologic and clinical characteristics of SFTS in South Korea.

Methods/Principal Findings

SFTS is a reportable disease in South Korea. We included all SFTS cases reported to the Korea Centers for Disease Control and Prevention (KCDC) from January 2013 to December 2015. Clinical information was gathered by reviewing medical records, and epidemiologic characteristics were analyzed using both KCDC surveillance data and patient medical records. Risk factors for mortality in patients with SFTS were assessed. A total of 172 SFTS cases were reported during the study period. SFTS occurred throughout the country, except in urban areas. Hilly areas in the eastern and southeastern regions and Jeju island (incidence, 1.26 cases /105 person-years) were the main endemic areas. The yearly incidence increased from 36 cases in 2013 to 81 cases in 2015. Most cases occurred from May to October. The overall case fatality ratio was 32.6%. The clinical progression was similar to the 3 phases reported in China: fever, multi-organ dysfunction, and convalescence. Confusion, elevated C-reactive protein, and prolonged activated partial thromboplastin times were associated with mortality in patients with SFTS. Two outbreaks of nosocomial SFTS transmission were observed.

Conclusions

SFTS is an endemic disease in South Korea, with a nationwide distribution and a high case-fatality ratio. Confusion, elevated levels of C-reactive protein, and prolonged activated partial thromboplastin times were associated with mortality in patients with SFTS.

]]>
<![CDATA[Severe Dengue Is Associated with Consumption of von Willebrand Factor and Its Cleaving Enzyme ADAMTS-13]]> https://www.researchpad.co/article/5989da69ab0ee8fa60b92764

Background

Thrombocytopenia, bleeding and plasma leakage are cardinal features of severe dengue. Endothelial cell activation with exocytosis of Weibel-Palade bodies (WPBs) may play an etiological role in this condition.

Methods and Principal Findings

In a cohort of 73 Indonesian children with dengue hemorrhagic fever (DHF), of which 30 with dengue shock syndrome (DSS), we measured plasma levels of the WPB constituents von Willebrand factor antigen (VWF:Ag), VWF propeptide and osteoprotegerin (OPG), together with activity levels of the VWF-cleaving enzyme ADAMTS-13 and the amount of VWF in a platelet binding conformation (VWF activation factor). Compared with healthy controls (n = 17), children with DHF/DSS had significantly higher levels of VWF:Ag, VWF propeptide and OPG and decreased ADAMTS-13 activity. The VWF activation factor was also significantly higher in DHF/DSS and highest in children who died. There were significant differences in the kinetics of the various WPB constituents: VWF propeptide and OPG levels decreased toward discharge, while VWF:Ag levels were lower than expected at enrollment with plasma levels increasing toward discharge. Moreover, VWF propeptide levels correlated better with markers of disease severity (platelet count, liver enzymes, serum albumin and pleural effusion index) than corresponding VWF levels. Together, these findings suggest that there is consumption of VWF in DHF/DSS. In 4 out of 15 selected children with low ADAMTS-13 levels on admission, we found a remarkable reduction in the large and intermediate VWF multimers in the discharge blood samples, consistent with an acquired von Willebrand disease.

Conclusion

These findings suggest that severe dengue is associated with exocytosis of WPBs with increased circulating levels of VWF:Ag, VWF propeptide and OPG. High circulating levels of VWF in its active conformation, together with low ADAMTS-13 activity levels, are likely to contribute to the thrombocytopenia and complications of dengue. During the convalescence phase, qualitative defects in VWF with loss of larger VWF multimers may develop.

]]>
<![CDATA[The Incidence, Clinical Outcomes, and Risk Factors of Thrombocytopenia in Intra-Abdominal Infection Patients: A Retrospective Cohort Study]]> https://www.researchpad.co/article/5989da62ab0ee8fa60b9146a

Background

Studies on the incidence and risk factors of thrombocytopenia among intra-abdominal infection patients remain absent, hindering efficacy assessments regarding thrombocytopenia prevention strategies.

Methods

We retrospectively studied 267 consecutively enrolled patients with intra-abdominal infections. Occurrence of thrombocytopenia was scanned for all patients. All-cause 28-day mortality was recorded. Variables from univariate analyses that were associated with occurrence of hospital-acquired thrombocytopenia were included in a multivariable logistic regression analysis to determine thrombocytopenia predictors.

Results

Median APACHE II score and SOFA score of the whole cohort was 12 and 3 respectively. The overall ICU mortality was 7.87% and the 28-day mortality was 8.98%. The incidence of thrombocytopenia among intra-abdominal infection patients was 21.73%. Regardless of preexisting or hospital-acquired one, thrombocytopenia is associated with an increased ICU mortality and 28-day mortality as well as length of ICU or hospital stay. A higher SOFA and ISTH score at admission were significant hospital-acquired thrombocytopenia risk factors.

Conclusions

This is the first study to identify a high incidence of thrombocytopenia in patients with intra-abdominal infections. Our findings suggest that the inflammatory milieu of intra-abdominal infections may uniquely predispose those patients to thrombocytopenia. More effective thrombocytopenia prevention strategies are necessary in intra-abdominal infection patients.

]]>
<![CDATA[Hematological Changes as Prognostic Indicators of Survival: Similarities Between Gottingen Minipigs, Humans, and Other Large Animal Models]]> https://www.researchpad.co/article/5989d9f9ab0ee8fa60b71231

Background

The animal efficacy rule addressing development of drugs for selected disease categories has pointed out the need to develop alternative large animal models. Based on this rule, the pathophysiology of the disease in the animal model must be well characterized and must reflect that in humans. So far, manifestations of the acute radiation syndrome (ARS) have been extensively studied only in two large animal models, the non-human primate (NHP) and the canine. We are evaluating the suitability of the minipig as an additional large animal model for development of radiation countermeasures. We have previously shown that the Gottingen minipig manifests hematopoietic ARS phases and symptoms similar to those observed in canines, NHPs, and humans.

Principal Findings

We establish here the LD50/30 dose (radiation dose at which 50% of the animals succumb within 30 days), and show that at this dose the time of nadir and the duration of cytopenia resemble those observed for NHP and canines, and mimic closely the kinetics of blood cell depletion and recovery in human patients with reversible hematopoietic damage (H3 category, METREPOL approach). No signs of GI damage in terms of diarrhea or shortening of villi were observed at doses up to 1.9 Gy. Platelet counts at days 10 and 14, number of days to reach critical platelet values, duration of thrombocytopenia, neutrophil stress response at 3 hours and count at 14 days, and CRP-to-platelet ratio were correlated with survival. The ratios between neutrophils, lymphocytes and platelets were significantly correlated with exposure to irradiation at different time intervals.

Significance

As a non-rodent animal model, the minipig offers a useful alternative to NHP and canines, with attractive features including ARS resembling human ARS, cost, and regulatory acceptability. Use of the minipig may allow accelerated development of radiation countermeasures.

]]>
<![CDATA[Phenotypic Expression of ADAMTS13 in Glomerular Endothelial Cells]]> https://www.researchpad.co/article/5989da73ab0ee8fa60b95aa1

Background

ADAMTS13 is the physiological von Willebrand factor (VWF)-cleaving protease. The aim of this study was to examine ADAMTS13 expression in kidneys from ADAMTS13 wild-type (Adamts13+/+) and deficient (Adamts13−/−) mice and to investigate the expression pattern and bioactivity in human glomerular endothelial cells.

Methodology/Principal Findings

Immunohistochemistry was performed on kidney sections from ADAMTS13 wild-type and ADAMTS13-deficient mice. Phenotypic differences were examined by ultramorphology. ADAMTS13 expression in human glomerular endothelial cells and dermal microvascular endothelial cells was investigated by real-time PCR, flow cytometry, immunofluorescence and immunoblotting. VWF cleavage was demonstrated by multimer structure analysis and immunoblotting. ADAMTS13 was demonstrated in glomerular endothelial cells in Adamts13+/+ mice but no staining was visible in tissue from Adamts13−/− mice. Thickening of glomerular capillaries with platelet deposition on the vessel wall was detected in Adamts13−/− mice. ADAMTS13 mRNA and protein were detected in both human endothelial cells and the protease was secreted. ADAMTS13 activity was demonstrated in glomerular endothelial cells as cleavage of VWF.

Conclusions/Significance

Glomerular endothelial cells express and secrete ADAMTS13. The proteolytic activity could have a protective effect preventing deposition of platelets along capillary lumina under the conditions of high shear stress present in glomerular capillaries.

]]>
<![CDATA[Mortality Predictors in Patients with Severe Dengue in the State of Amazonas, Brazil]]> https://www.researchpad.co/article/5989dab3ab0ee8fa60bac27e

Dengue is a major public health problem in tropical and subtropical areas worldwide. There is a lack of information on the risk factors for death due to severe dengue fever in developing countries, including Brazil where the state of Amazonas is located. This knowledge is important for decision making and the implementation of effective measures for patient care. This study aimed to identify factors associated with death among patients with severe dengue, in Amazonas from 2001 to 2013. We conducted a retrospective cohort study based on secondary data from the epidemiological surveillance of dengue provided by the Fundação de Vigilância em Saúde do Amazonas, FVS (Health Surveillance Foundation) of the Secretaria de Saúde do Amazonas, SUSAM (Health Secretariat of the State of Amazonas). Data on dengue cases were obtained from the SINAN (Notifiable Diseases Information System) and SIM (Mortality Information System) databases. We selected cases of severe dengue with laboratory confirmation, including dengue-related deaths of residents in the state of Amazonas from January 1, 2001, to December 31, 2013. The explanatory variables analyzed were sex, age, level of education, spontaneous hemorrhagic manifestations, plasma extravasation and platelet count. Patients who died due to severe dengue had more hematuria, gastrointestinal bleeding, and thrombocytopenia than the survivors. Considering the simultaneous effects of demographic and clinical characteristics with a multiple logistic regression model, it was observed that the factors associated with death were age >55 years (odds ratio [OR] 4.98), gastrointestinal bleeding (OR 10.26), hematuria (OR 5.07), and thrombocytopenia (OR 2.55). Gastrointestinal bleeding was the clinical sign most strongly associated with death, followed by hematuria and age >55 years. The study results showed that the best predictor of death from severe dengue is based on the characteristic of age >55 years, together with the clinical signs of gastrointestinal bleeding, hematuria, and low platelet count.

]]>
<![CDATA[Efficacy and Safety of Lenalidomide for Treatment of Low-/Intermediate-1-Risk Myelodysplastic Syndromes with or without 5q Deletion: A Systematic Review and Meta-Analysis]]> https://www.researchpad.co/article/5989daa3ab0ee8fa60ba6896

Background

Lenalidomide could effectively induce red blood cell (RBC) transfusion independence (TI) in patients with lower-risk (Low/Intermediate-1) myelodysplastic syndrome (MDS) with or without 5q deletion. However whether lenalidomide ultimately improves the overall survival (OS) of lower-risk MDS patients and reduces the progression to AML remains controversial.

Method

A meta-analysis was conducted to examine the efficacy and safety of lenalidomide in the treatment of lower-risk MDS. Efficacy was assessed according to erythroid hematologic response (HI-E), cytogenetic response (CyR), OS and AML progression. Safety was evaluated based on the occurrence rates of grades 3–4 adverse events (AEs).

Results

Seventeen studies were included consisting of a total of 2160 patients. The analysis indicated that the overall rate of HI-E was 58% with 95% confidence interval (CI) of 43–74%. The pooled estimates for the rates of CyR, complete CyR, and partial CyR were 44% (95% CI 19–68%), 21% (95% CI 13–30%) and 23% (95% CI 15–32%), respectively. The patients with 5q deletion had significantly higher rate of HI-E and CyR than those without 5q deletion (P = 0.002 and 0.001, respectively). The incidences of grades 3–4 neutropenia, thrombocytopenia, leukopenia, anemia, deep vein thrombosis, diarrhea, fatigue and rash were 51% (95% CI 30–73%), 31% (95% CI 20–42%), 9% (95% CI 5–13%), 7% (95% CI 2–12%), 3% (95% CI 2–5%), 3% (95% CI 1–5%), 2% (95% CI 1–4%) and 2% (95% CI 1–3%), respectively. Lenalidomide significantly improved OS (HR: 0.62, 95% CI 0.47–0.83, P = 0.001) and lowered the risk of AML progression in del(5q) patients (RR: 0.61, 95% CI 0.41–0.91, P = 0.014).

Conclusions

In spite of the AEs, lenalidomide could be effectively and safely used for the treatment of lower-risk MDS patients with or without 5q deletion.

]]>
<![CDATA[Repercussion of Megakaryocyte-Specific Gata1 Loss on Megakaryopoiesis and the Hematopoietic Precursor Compartment]]> https://www.researchpad.co/article/5989da6bab0ee8fa60b92eb6

During hematopoiesis, transcriptional programs are essential for the commitment and differentiation of progenitors into the different blood lineages. GATA1 is a transcription factor expressed in several hematopoietic lineages and essential for proper erythropoiesis and megakaryopoiesis. Megakaryocyte-specific genes, such as GP1BA, are known to be directly regulated by GATA1. Mutations in GATA1 can lead to dyserythropoietic anemia and pseudo gray-platelet syndrome. Selective loss of Gata1 expression in adult mice results in macrothrombocytopenia with platelet dysfunction, characterized by an excess of immature megakaryocytes. To specifically analyze the impact of Gata1 loss in mature committed megakaryocytes, we generated Gata1-Lox|Pf4-Cre mice (Gata1cKOMK). Consistent with previous findings, Gata1cKOMK mice are macrothrombocytopenic with platelet dysfunction. Supporting this notion we demonstrate that Gata1 regulates directly the transcription of Syk, a tyrosine kinase that functions downstream of Clec2 and GPVI receptors in megakaryocytes and platelets. Furthermore, we show that Gata1cKOMK mice display an additional aberrant megakaryocyte differentiation stage. Interestingly, these mice present a misbalance of the multipotent progenitor compartment and the erythroid lineage, which translates into compensatory stress erythropoiesis and splenomegaly. Despite the severe thrombocytopenia, Gata1cKOMK mice display a mild reduction of TPO plasma levels, and Gata1cKOMK megakaryocytes show a mild increase in Pf4 mRNA levels; such a misbalance might be behind the general hematopoietic defects observed, affecting locally normal TPO and Pf4 levels at hematopoietic stem cell niches.

]]>
<![CDATA[Serological and Entomological Study of Dengue in Dang and Chitwan Districts of Nepal]]> https://www.researchpad.co/article/5989dad2ab0ee8fa60bb6af1

A descriptive cross-sectional study was carried out among 264 suspected dengue patients in two districts (Dang and Chitwan) of Nepal from June 2013 to November 2013. The anti-dengue IgM positivity was found to be (51/264)19.31% by capture ELISA, of which 21 (41.2%) were male and 30 (58.8%) were female. Symptoms of seropositive cases were fever, anorexia, nausea, headache, retro-orbital pain, skin rashes, and myalgia. Hematological features like thrombocytopenia and leucopenia were found to be significantly associated with the dengue fever (DF). Discarded tires were found as the commonest breeding habitats for the dengue vectors. Higher sero-positivity was recorded from the area having higher Breteau index (BI). The pH, chloride ion concentration and the salinity of the water from breeding habitats were found to be ranging from 6.9±0.82 to 8, 103.33±17.52 mg/L to 140.65 mg/L, and 0.19±0.032 ppt to 0.25 ppt respectively. This study may be helpful for the health authorities and public health workers for early diagnosis of DF and for the improved preventive measures to be adopted in the epidemic and possible epidemic areas.

]]>
<![CDATA[Alteration of Liver Enzymes Is a Feature of the Myh9-Related Disease Syndrome]]> https://www.researchpad.co/article/5989db17ab0ee8fa60bcd641

Background

MYH9-related disease (MYH9-RD) is a rare autosomal dominant genetic syndrome characterized by congenital thrombocytopenia associated with the risk of developing progressive nephropathy, sensorineural deafness, and presenile cataract. During the collection of a large case-series of patients with MYH9-RD we noticed several cases with unexplained elevation of liver enzymes. Our aim was to evaluate if the alteration of liver tests is a feature of the MYH9-RD and to define its clinical significance.

Methods and Findings

Data concerning liver tests, prospectively recorded in the Italian Registry for MYH9-RD, were collected and compared with those of three control populations: patients with autoimmune thrombocytopenia, patients with inherited thrombocytopenias other than MYH9-RD, and the participants to a large epidemiologic survey in an Italian geographic isolate. Thirty-eight of 75 evaluable MYH9-RD patients (50.7%) showed an elevation of ALT and/or AST, and 17 of 63 (27.0%) an increase of GGT. The increases ranged from 1.9±0.7 to 2.7±1.6 fold the upper normal limit. The prevalence of liver test alterations was significantly higher in MYH9-RD patients than in each of the control populations, with odds ratios ranging from 8.2 (95% CIs 2.2–44.8) to 24.7 (14.8–40.8). Clinical follow-up and more detailed liver studies of a subset of patients, including ultrasound liver scan, liver elastography and liver biopsy in one case, did not show any significant structural damage or evolution towards liver insufficiency.

Conclusions

Elevation of liver enzymes is a frequent and previously unrecognized feature of the MYH9-RD syndrome; however, this defect does not appear to have poor prognostic value.

]]>
<![CDATA[Severe Fever with Thrombocytopenia Syndrome Virus Antigen Detection Using Monoclonal Antibodies to the Nucleocapsid Protein]]> https://www.researchpad.co/article/5989da31ab0ee8fa60b846e5

Background

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease with a high case fatality rate, and is caused by the SFTS virus (SFTSV). SFTS is endemic to China, South Korea, and Japan. The viral RNA level in sera of patients with SFTS is known to be strongly associated with outcomes. Virological SFTS diagnosis with high sensitivity and specificity are required in disease endemic areas.

Methodology/Principal Findings

We generated novel monoclonal antibodies (MAbs) against the SFTSV nucleocapsid (N) protein and developed a sandwich antigen (Ag)-capture enzyme-linked immunosorbent assay (ELISA) for the detection of N protein of SFTSV using MAb and polyclonal antibody as capture and detection antibodies, respectively. The Ag-capture system was capable of detecting at least 350–1220 TCID50/100 μl/well from the culture supernatants of various SFTSV strains. The efficacy of the Ag-capture ELISA in SFTS diagnosis was evaluated using serum samples collected from patients suspected of having SFTS in Japan. All 24 serum samples (100%) containing high copy numbers of viral RNA (>105 copies/ml) showed a positive reaction in the Ag-capture ELISA, whereas 12 out of 15 serum samples (80%) containing low copy numbers of viral RNA (<105 copies/ml) showed a negative reaction in the Ag-capture ELISA. Among these Ag-capture ELISA-negative 12 samples, 9 (75%) were positive for IgG antibodies against SFTSV.

Conclusions

The newly developed Ag-capture ELISA is useful for SFTS diagnosis in acute phase patients with high levels of viremia.

]]>