SummaryThere is a need for improved treatment of patients with chronic hepatitis B (CHB). We reviewed the literature to explore the efficacy of HB vaccines alone or in combination therapy (CT) with antiviral drugs in CHB patients and to meta‐analyze data from randomized controlled trials. We conducted a systematic search in ten databases. All studies investigating the efficacy of HBV vaccine in HBV infected patients were included with no restrictions. Among 1359 studies initially identified, 23 studies (n = 1956 patients) were included for the final analysis. CT showed a significant reduction of HBV DNA compared with analogue monotherapy (AM) at the 12‐month follow‐up period (odds ratio (OR) = 2.835, 95% confidence interval (CI) [1.275, 6.306], p = .011). Additionally, CT also remarkably induce HbsAg loss in comparison with AM (OR = 11.736, 95% CI [1.841, 74.794], p = .009). Our pooled data revealed no difference between treatment and control regarding alanine aminotransferase normalization, HBeAg seroconversion, and HBeAg disappearance. In addition, CT using vaccine and NAs resulted in a statistically significant higher incidence of adverse effects than AM. The therapeutic effects of combination therapy for patients with CHB were encouraging, but future studies need to investigate all possible treatment combinations and assess their cost‐effectiveness.

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Background We aimed to investigate the prognostic role of examined (dissected) lymph nodes (ELNs), negative LNs (NLNs), and positive (metastatic) LNs (PLNs) counts and LN ratio (LNR = PLNs/ELNs×100) in patients with major salivary gland cancer (SGC). Methods Data were retrieved for major SGC patients diagnosed between 1988 and 2011 from Surveillance, Epidemiology, and End Results program. Results We have included 5446 patients with major SGC. Most patients had parotid gland cancer (84.61%). Patients having >18 ELNs, >4 PLNs, and >33.33% LNR were associated with a worse survival. Moreover, older age, male patients, grade IV, distant stage, unmarried patients, submandibular gland cancer, and received chemotherapy but not received surgery were significantly associated with a worse survival. Conclusions We demonstrated that patients with >18 ELNs and >4 PLNs counts, and >33.33% LNR were high‐risk group patients. We strongly suggest adding the ELNs and PLNs counts and/or LNR into the current staging system.

SummaryBackgroundDegranulation of mast cells (MCs) releases several mediators such as vascular endothelial growth factor (VEGF), chymase, tryptase, histamine, and cytokines, which all have important roles in the severity of dengue infection. We aimed to investigate the role of MCs in severity of dengue.MethodsWe searched for relevant studies in 10 databases on 15 August 2016. Meta‐analysis (MA) was conducted by R version 3.5.0.ResultsWe included 24 studies. in vivo and in vitro studies showed higher MC products released from infected mice/cells with dengue virus. In addition, when administering MC stabilizers or antihistaminic drugs, there was a decrease in vascular/capillary permeability. In human and at early stages, studies revealed an insignificant difference in VEGF levels in dengue fever (DF) versus dengue hemorrhagic fever (DHF) (standardized mean difference [SMD] 0.145; 95% confidence interval [CI], −0.348‐0.638). Meanwhile, at acute stages and compared with healthy controls, high heterogeneity with an inconclusive difference in VEGF levels were noted in DF and DHF. However, pooled serum and plasma levels of VEGF were increased significantly in dengue shock syndrome (DSS) versus healthy controls (SMD 0.65; 95% CI, 0.3‐0.95). There were also significantly higher chymase levels in DHF patients compared with DF during the acute phase (MD −6.531; 95% CI, −12.2 to −0.9).ConclusionVEGF and chymase levels are mediators in dengue pathogenesis. However, limited data were available to support their role in severe dengue cases. Further studies are needed to evaluate the function of other mediators in dengue severity.

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.

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BackgroundConsiderable progress has been made in dengue management, however the lack of appropriate predictors of severity has led to huge number of unwanted admissions mostly decided on the grounds of warning signs. Apoptosis related mediators, among others, are known to correlate with severe dengue (SD) although no predictive validity is established. The objective of this study was to investigate the association of plasma cell-free DNA (cfDNA) with SD, and evaluate its prognostic value in SD prediction at acute phase.MethodsThis was a hospital-based prospective cohort study conducted in Vietnam. All the recruited patients were required to be admitted to the hospital and were strictly monitored for various laboratory and clinical parameters (including progression to SD) until discharged. Plasma samples collected during acute phase (6–48 h before defervescence) were used to estimate the level of cfDNA.ResultsOf the 61 dengue patients, SD patients (n = 8) developed shock syndrome in 4.8 days (95% CI 3.7–5.4) after the fever onset. Plasma cfDNA levels before the defervescence of SD patients were significantly higher than the non-SD group (p = 0.0493). From the receiver operating characteristic (ROC) curve analysis, a cut-off of > 36.9 ng/mL was able to predict SD with a good sensitivity (87.5%), specificity (54.7%), and area under the curve (AUC) (0.72, 95% CI 0.55–0.88; p = 0.0493).ConclusionsTaken together, these findings suggest that cfDNA could serve as a potential prognostic biomarker of SD. Studies with cfDNA kinetics and its combination with other biomarkers and clinical parameters would further improve the diagnostic ability for SD.Electronic supplementary materialThe online version of this article (10.1186/s12941-019-0309-x) contains supplementary material, which is available to authorized users.

ObjectivesThis study aimed to investigate the knowledge, behaviour and attitudes towards Chagas disease (CD) among Latin American migrants in Japan and to evaluate the effectiveness of an educational activity (EA) in increasing knowledge of CD.DesignA cross-sectional, mixed-methods study employing a preknowledge and postknowledge test and focus group discussion, conducted from March 2018 to June 2018.ParticipantsSeventy-two participants were included, all born in Bolivia and residents in four Japanese cities. Fifty-nine of them participated in the EA.InterventionsThe EA comprised showing three videos about CD and a group discussion covering different dimensions of CD and was evaluated with questionnaires to analyse the knowledge of the participants before and after.ResultsSeventy-two participants were enrolled, predominantly from highly endemic CD areas of Bolivia. Though most participants were familiar with vector-borne transmission, epidemiology and symptomatology of CD, the baseline knowledge of CD was low. Less than 10% of them had been tested prior for CD. The dominant factors associated with better knowledge were living in Japan for more than 10 years (OR=8.42, 95% CI 1.56 to 48.62) and previously testing for CD (OR=11.32; 95% CI 1.52 to 105.9). The EA significantly improved the CD knowledge of the participants (p value <0.0001; 95% CI 2.32 to 3.84). The participants associated the term ‘Chagas’ mostly with fear and concern. The level of stigmatisation was low, in contrast to the results of other studies. The barriers encountered in care-seeking behaviour were language, the migration process and difficulties to access the healthcare system.ConclusionEA with an integrative approach is useful to increase the knowledge of CD within the Bolivian migrant population living in Japan. The activity brings the possibility to explore not only the level of knowledge but also to reveal experiences and to understand the needs of the people at risk. Considering them as actors towards healthcare solutions could lead to better outcomes for the success of future policies and interventions aimed to decrease the global burden.