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Thrombosis is a well-known complication in children with acute lymphoblastic leukemia (ALL) with a reported frequency of up to 36.7%, resulting in significant morbidity and mortality. Children with ALL were found to have persistent increased thrombin generation following diagnosis, yet, the pathogenesis and impact of therapy on thrombin activation are still unknown. Athale et al. previously demonstrated an association between the presence of peripheral lymphoblasts with increased levels of Von Willebrand Factor and parameters of thrombin generation. The objective of this study is to confirm the clinical observation in an in vitro co-culture model and to explore the effect of lymphoblasts on hemostasis. Human umbilical vein endothelial cells were co-cultured with peripheral-blood derived lymphoblasts in reduced serum media. Biomarkers of endothelial activation and the expression of endothelial products involved in hemostasis were measured by enzyme-linked immunosorbent assays. Endothelial health was evaluated by endothelial permeability assay and LDH cytotoxicity assay. Thrombin generation on the endothelial surface was monitored with a thrombin substrate. The clotting time of plasma mixed with supernatants derived from lymphoblasts was measured by a plasma recalcification assay. Compared to unstimulated endothelium, the presence of leukemic lymphoblasts significantly increased biomarkers of endothelial activation including VWF and adhesion molecules. In addition, the expression of endothelial products involved in hemostasis was altered towards a prothrombotic phenotype. On endothelium cocultured with leukemic blasts, plasma clotting time was faster, and increased thrombin generation was recorded. When mixed with plasma, secretants from leukemic lymphoblasts increased parameters of thrombin generation. In conclusion, we confirmed the clinical observation that peripheral blasts are capable of activating endothelium, leading to the elevation of VWF; and may cause the prothrombotic state seen in children with acute lymphoblastic leukemia. Thesis Master of Science (MSc)

[This corrects the article DOI: 10.1371/journal.pntd.0009808.].

Vestibular schwannoma is a benign tumor in the schwannoma cells of the 8th cranial nerve. It causes symptoms like tinnitus, vertigo and end up with loss of hearing so the appropriate treatment is very important. There are many treatment techniques including conservative, surgery and radiosurgery. We aimed to systematically review and single arm meta-analysis the different treatment techniques of vestibular schwannoma.A comprehensive literature search using thirteen databases including PubMed, Scopus, and Web of Science was performed. All clinical trials about treatment vestibular schwannoma were included and single arm meta-analyzed. We assessed the risk of bias using ROBIN-I's tool and scale of Council Australia's Cancer Guidelines Wiki. The protocol was registered in PROSPERO (CRD42018089784) and has been updated on 17 April 2019.A total of 35 clinical trials studies were included in the final analysis. The pooled proportion of stable hearing capability in patients receiving gamma knife radiosurgery (GKRS) was 64% (95% CI: 52%-74%). GKRS favored increased hearing capability 10% (95% CI: 7%-16%). Regarding tumor size, GKRS is the most protective method 53% (95% CI: 37%-69%). Complications occurred most commonly in single fractional linac stereotactic radiosurgery (SFSRT) 37% (95% CI: 12%-72%).Our analysis suggested gamma knife radiosurgery could be the most ideal treatment for vestibular schwannoma based on stabilizing hearing capability, increasing hearing capability, decreasing tumor size and complications.

Background: Alanine aminotransferase (ALT) is a marker of hepatic damage and its range can be affected by viral hepatitis, alcoholic hepatitis and non-alcoholic fatty liver diseases. We aimed to study the factors associated with higher ALT level and update the upper limit of normal (ULN) in the Vietnamese population. Methods: This cross-sectional study enrolled 8383 adults, aged 18 years and older who visited the Medical Center at Ho Chi Minh City for a health check-up. Following the exclusion criteria, 6677 subjects were included in the analysis. Results: Age ≤40 years, male gender, body mass index >23 kg/m2, diastolic blood pressure >85 mm Hg, cholesterol >5.2 mmol/L, triglyceride >1.7 mmol/L, positivity, anti-hepatitis C virus positivity and fatty liver (p40 U/L). Without considering age and gender, healthy group is defined after exclusion of participants with one of the mentioned contributing factors. The median ALT level in the healthy group was 18 in men and 13 in women. The ULN at the 95th percentile of the healthy group was 40 U/L in men and 28 U/L in women. Conclusion: The ULN for ALT in healthy women was lower than in healthy men. Updated ULN for ALT level can promote the identification of unhealthy subjects. More studies that involve ethnicity and lifestyle factors are needed to confirm the new ULN in the Vietnamese population., BMJ Open Gastroenterology, 9(1), art. no. e000870; 2022

Background Predictive markers represent a solution for the proactive management of severe dengue. Despite the low mortality rate resulting from severe cases, dengue requires constant examination and round-the-clock nursing care due to the unpredictable progression of complications, posing a burden on clinical triage and material resources. Accordingly, identifying markers that allow for predicting disease prognosis from the initial diagnosis is needed. Given the improved pathogenesis understanding, myriad candidates have been proposed to be associated with severe dengue progression. Thus, we aim to review the relationship between the available biomarkers and severe dengue. Methodology We performed a systematic review and meta-analysis to compare the differences in host data collected within 72 hours of fever onset amongst the different disease severity levels. We searched nine bibliographic databases without restrictive criteria of language and publication date. We assessed risk of bias and graded robustness of evidence using NHLBI quality assessments and GRADE, respectively. This study protocol is registered in PROSPERO (CRD42018104495). Principal findings Of 4000 records found, 40 studies for qualitative synthesis, 19 for meta-analysis. We identified 108 host and viral markers collected within 72 hours of fever onset from 6160 laboratory-confirmed dengue cases, including hematopoietic parameters, biochemical substances, clinical symptoms, immune mediators, viral particles, and host genes. Overall, inconsistent case classifications explained substantial heterogeneity, and meta-analyses lacked statistical power. Still, moderate-certainty evidence indicated significantly lower platelet counts (SMD -0.65, 95% CI -0.97 to -0.32) and higher AST levels (SMD 0.87, 95% CI 0.36 to 1.38) in severe cases when compared to non-severe dengue during this time window. Conclusion The findings suggest that alterations of platelet count and AST level—in the first 72 hours of fever onset—are independent markers predicting the development of severe dengue., Author summary The major concern in dengue fever is the abrupt occurrence of severe complications, for which only close monitoring of patients is the treatment scheme. Thus, the markers managing to predict the subsequent progression of complications—in the early stage of disease course—could alleviate the clinical management burden. Ideally, the predictors foretell the outcomes before the severe complications occur—usually on days 4–7 following fever onset. In this study, therefore, we reviewed the available markers collected during the first 3 days of fever onset. We found robust evidence of significantly lower platelet counts and higher AST levels in those who subsequently developed severe dengue than those who did not. In this regard, platelet count could serve as an independent warning sign rather than combining with hematocrit—as seen in the current classification—which remains unaltered during this time window. Also, abdominal pain and vomiting could predict the outcomes, but using these signs is arduous when their manifestations vary as per the patient without cutoffs. Hepatomegaly rate is substantially higher in severe dengue, but likely yields a high false-negative prediction rate. There is a need for larger studies to confirm the relatedness of hyaluronan in severe dengue.

BackgroundChagas disease (CD), typically confined to the Latin America (LA) region, is emerging as a global health problem. In Japan, as in the rest of world, the under-diagnose rate of CD is alarmingly high. Various studies have highlighted the importance of informed knowledge in the seeking behavior. Educational integrative activities, with consideration for socio-cultural factors, can help increase the knowledge of the participants. There has been no studies that analyze the difference in knowledge, before and after these educational activities. This study aimed to qualitatively and quantitatively investigate the knowledge, behavior and attitude toward CD among LA migrants in Japan and to evaluate the effectiveness of the community educational activity in increasing knowledge of CD.MethodologyThis cross-sectional study involved two questionnaires to analyze the knowledge of the LA migrant participants before and after the community activity (CA) in four cities in Japan (Oizumi, Suzuka, Hadano, and Nagoya).Principal FindingsA total of 75 participants were enrolled, predominantly Bolivians from hyperendemic areas. The baseline knowledge of CD was low. However, most of them were familiar with the disease although less than 10% of them had been tested for CD before. Living in Japan for more than 10 years and previously being tested for CD were the factors associated with better knowledge. The conducted CA significantly improved the knowledge of the participants. They associated the term “Chagas” mostly with fear and concern. In contrast to other studies, the level of stigmatization was low. The barriers in care seeking behavior were language, migration process and difficulties to access to the healthcare system.ConclusionEducational activities with integrative approach are useful to increase knowledge of CD. The activity brings the possibility to explore not only the level of knowledge, but also to reveal the experience and to understand the needs of the people at risk.Author SummaryThough the incident rate of Chagas disease (CD) has fallen, more than 7 million people are affected worldwide. The CD prevalence is under-estimated because just 1% of these affected people can access to the diagnosis and treatment. This situation is maintaining mainly for the lack of implication of socio-cultural factors in the interventions to decrease the burden of the disease. Educational activities with integral approach are useful to increase the knowledge of the people at risk. People that have being tested for CD before or living in Japan for more than 10 years have better knowledge about the disease, suggesting the importance of knowledge in the seeking behavior. The authors recommend the implementation of educational activities with integral approach as a strategy to improves the knowledge of Chagas disease among Latin America migrants in Japan.