Endothelial and inflammatory pathophysiology in dengue shock: New insights from a prospective cohort study in Vietnam.

Dengue shock (DS) is the most severe complication of dengue infection; endothelial hyperpermeability leads to profound plasma leakage, hypovolaemia and extravascular fluid accumulation. At present, the only treatment is supportive with intravenous fluid, but targeted endothelial stabilising therapies and host immune modulators are needed. With the aim of prioritising potential therapeutics, we conducted a prospective observational study of adults (≥16 years) with DS in Vietnam from 2019-2022, comparing the pathophysiology underlying circulatory failure with patients with septic shock (SS), and investigating the association of biomarkers with clinical severity (SOFA score, ICU admission, mortality) and pulmonary vascular leak (daily lung ultrasound for interstitial and pleural fluid). Plasma was collected at enrolment, 48 hours later and hospital discharge. We measured biomarkers of inflammation (IL-6, ferritin), endothelial activation (Ang-1, Ang-2, sTie-2, VCAM-1) and endothelial glycocalyx breakdown (hyaluronan, heparan sulfate, endocan, syndecan-1). We enrolled 135 patients with DS (median age 26, median SOFA score 7, 34 required ICU admission, 5 deaths), together with 37 patients with SS and 25 healthy controls. Within the DS group, IL-6 and ferritin were associated with admission SOFA score (IL-6: ßeta0.70, p<0.001 & ferritin: ßeta0.45, p<0.001), ICU admission (IL-6: OR 2.6, p<0.001 & ferritin: OR 1.55, p<0.001) and mortality (IL-6: OR 4.49, p = 0.005 & ferritin: OR 13.8, p = 0.02); both biomarkers discriminated survivors and non-survivors at 48 hours and all patients who died from DS had pre-mortem ferritin ≥100,000ng/ml. IL-6 most strongly correlated with severity of pulmonary vascular leakage (R = 0.41, p<0.001). Ang-2 correlated with pulmonary vascular leak (R = 0.33, p<0.001) and associated with SOFA score (ß 0.81, p<0.001) and mortality (OR 8.06, p = 0.002). Ang-1 was associated with ICU admission (OR 1.6, p = 0.005) and mortality (OR 3.62, p = 0.006). All 4 glycocalyx biomarkers were positively associated with SOFA score, but only syndecan-1 was associated with ICU admission (OR 2.02, p<0.001) and mortality (OR 6.51, p<0.001). This study highlights the central role of hyperinflammation in determining outcomes from DS; the data suggest that anti-IL-1 and anti-IL-6 immune modulators and Tie2 agonists may be considered as candidates for therapeutic trials in severe dengue.

Predicting Anxiety and Depression Among Erectile Dysfunction Patients: A Cross-Sectional Study.

In Vietnam, erectile dysfunction (ED) is prevalent and recognized to be associated with mental disorders; however, societal taboos impede a comprehensive understanding of this connection. Our study aims to investigate the factors related to higher levels of anxiety and/or depression (HAD) in individuals with ED. Between November 2022 and March 2023, a face-to-face survey was conducted at the Center for Andrology of Viet Duc University Hospital, involving 390 patients diagnosed with ED. The survey included 51 questions covering general patient information, the International Index of Erectile Function-15 (IIEF-15), the Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder-7 (GAD-7). The stepwise Akaike Information Criterion (AIC) method was used to identify factors associated with HAD. The study revealed an average age of 37.63 (11.84) years among participants, with a HAD prevalence of 17.69%. Several factors were associated with a higher likelihood of belonging to the HAD group in ED patients. These factors included non-office workers (OR: 1.11; 95% CI: [1.01, 1.21], p = .025), medium and high levels of work-related stress (OR: 1.23; [1.06, 1.44], p = .008; OR: 1.22; [1.04, 1.45], p = .018), multiple shameful experiences related to ED (OR: 1.16; [1.08, 1.25], p < .001), moderate and severe ED (OR: 1.17; [1.03, 1.32], p = .013; OR: 1.31; [1.14, 1.51], p < .001), and dissatisfaction with intercourse skills (OR: 1.09; [1.01, 1.17], p = .028). Our findings suggest a 16% higher likelihood of HAD status in individuals with multiple shameful experiences related to ED, while moderate and severe ED are associated with respective increases of 17% and 31% in the likelihood. These findings emphasize the importance of considering mental health in the care of individuals with ED.

A modified Sequential Organ Failure Assessment score for dengue: development, evaluation and proposal for use in clinical trials.

BACKGROUND: Dengue is a neglected tropical disease, for which no therapeutic agents have shown clinical efficacy to date. Clinical trials have used strikingly variable clinical endpoints, which hampers reproducibility and comparability of findings. We investigated a delta modified Sequential Organ Failure Assessment (delta mSOFA) score as a uniform composite clinical endpoint for use in clinical trials investigating therapeutics for moderate and severe dengue. METHODS: We developed a modified SOFA score for dengue, measured and evaluated its performance at baseline and 48 h after enrolment in a prospective observational cohort of 124 adults admitted to a tertiary referral hospital in Vietnam with dengue shock. The modified SOFA score included pulse pressure in the cardiovascular component. Binary logistic regression, cox proportional hazard and linear regression models were used to estimate association between mSOFA, delta mSOFA and clinical outcomes. RESULTS: The analysis included 124 adults with dengue shock. 29 (23.4%) patients required ICU admission for organ support or due to persistent haemodynamic instability: 9/124 (7.3%) required mechanical ventilation, 8/124 (6.5%) required vasopressors, 6/124 (4.8%) required haemofiltration and 5/124 (4.0%) patients died. In univariate analyses, higher baseline and delta (48 h) mSOFA score for dengue were associated with admission to ICU, requirement for organ support and mortality, duration of ICU and hospital admission and IV fluid use. CONCLUSIONS: The baseline and delta mSOFA scores for dengue performed well to discriminate patients with dengue shock by clinical outcomes, including duration of ICU and hospital admission, requirement for organ support and death. We plan to use delta mSOFA as the primary endpoint in an upcoming host-directed therapeutic trial and investigate the performance of this score in other phenotypes of severe dengue in adults and children.

Diagnostic and prognostic value of miR-200 family in breast cancer: A meta-analysis and systematic review.

BACKGROUND: Breast cancer (BC) is the most common cancer for women all over the world. Great interests have been paid to discover accurate and noninvasive methods for breast cancer diagnosis and prognosis. Although the diagnostic and prognostic value of microRNA-200 (miRNA- 200, miR-200) family has been revealed in many studies, the results were inconsistent. Thus, this meta-analysis aims to assess the overall value of miRNA-200 family in breast cancer diagnosis and prognosis. METHOD: Relevant studies were searched from the following databases: PubMed, PMC, EMBASE, and ScienceDirect using key words: ("miRNA-200 family" or "miR-141" or "miR-200a" or "miR-200b" or "miR-200c" or "miR-429") and ("HER2" or "Luminal A" or "Luminal B" or "TNBC") and ("breast cancers" or "breast carcinoma" or "breast malignancy" or "breast tumor"). The sensitivity, specificity, AUC were then calculated to estimate the diagnostic accuracy of the miR-200 family. As for the prognostic value of the miR-200 family, the pooled hazard ratio (HR) was assessed. Heterogeneity among individual studies was also examined by subgroup analyses. RESULT: A total of 24 articles were included in the meta-analysis. The diagnostic value of miR-200s in BC was presented by the pooled sensitivity was 0.86 (95% CI: 0.83-0.88); the pooled specificity was 0.82 (95% CI: 0.72-0.89); the pooled AUC was 0.931 (95% CI: 0.919-0.942). Besides, expression of miR-200s in metastatic breast cancer has sensitivity, specificity and AUC of 0.70 (95%CI: 0.56-0.81), 0.72 (95%CI: 0.61-0.81), and 0.814 (95%CI: 0.741-0.903), respectively. The meta-analysis then revealed that high expression of miR-200 family corresponded to poor OS (HR: 1.63, 95% CI: 1.03-2.52), poor DFS (HR: 1.55, 95% CI: 0.95-2.56) in BC patients while downregulation of miRNA-200s corresponded to poor OS (HR= 0.84, 95%CI: 0.46-1.63) in TNBC patients and poor OS (HR=0.49; 95%CI: 0.27-0.88) in luminal BC patient. CONCLUSION: The MiR-200 family has high diagnostic accuracy and can be used as an important biomarker to prognosticate breast cancer.