Acute venous thromboembolism plasma and red blood cell metabolomic profiling reveals potential new early diagnostic biomarkers: observational clinical study.

BACKGROUND: Venous thromboembolism (VTE) is a leading cause of cardiovascular mortality. The diagnosis of acute VTE is based on complex imaging exams due to the lack of biomarkers. Recent multi-omics based research has contributed to the development of novel biomarkers in cardiovascular diseases. Our aim was to determine whether patients with acute VTE have differences in the metabolomic profile compared to non-acute VTE. METHODS: This observational trial included 62 patients with clinical suspicion of acute deep vein thrombosis or pulmonary embolism, admitted to the emergency room. There were 50 patients diagnosed with acute VTE and 12 with non-acute VTE conditions and no significant differences were found between the two groups for clinical and demographic characteristics. Metabolomics assays identified and quantified a final number of 91 metabolites in plasma and 55 metabolites in red blood cells (RBCs). Plasma from acute VTE patients expressed tendency to a specific metabolomic signature, with univariate analyses revealing 23 significantly different molecules between acute VTE patients and controls (p < 0.05). The most relevant metabolic pathway with the strongest impact on the acute VTE phenotype was D-glutamine and D-glutamate (p = 0.001, false discovery rate = 0.06). RBCs revealed a specific metabolomic signature in patients with a confirmed diagnosis of DVT or PE that distinguished them from other acutely diseased patients, represented by 20 significantly higher metabolites and four lower metabolites. Three of those metabolites revealed high performant ROC curves, including adenosine 3',5'-diphosphate (AUC 0.983), glutathione (AUC 0.923), and adenine (AUC 0.91). Overall, the metabolic pathway most impacting to the differences observed in the RBCs was the purine metabolism (p = 0.000354, false discovery rate = 0.68). CONCLUSIONS: Our findings show that metabolite differences exist between acute VTE and nonacute VTE patients admitted to the ER in the early phases. Three potential biomarkers obtained from RBCs showed high performance for acute VTE diagnosis. Further studies should investigate accessible laboratory methods for the future daily practice usefulness of these metabolites for the early diagnosis of acute VTE in the ER.

Comparison of diuretics and fluid expansion in the initial treatment of patients with normotensive acute pulmonary embolism: a systematic review and meta-analysis.

BACKGROUND: Right ventricular (RV) dysfunction is the main cause of death in patients with normotensive acute pulmonary embolism (PE). The optimal management for this subset of patients remains uncertain. This systematic review and meta-analysis focused on the comparison of diuretics and fluid expansion in patients with acute PE presenting with RV dysfunction and haemodynamic stability. METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines considering only RTCs. The authors searched the traditional and grey literature through 1 November 2022. Meta-analysis used open source packages in R. Inverse variance fixed-effects models with OR as the effect measure were used for primary analyses. The main outcomes defined in this review protocol included pulmonary arterial systolic pressure (PASP), creatinine value changes and N-terminal pro-B-type natriuretic peptide during the first 24 hours. RESULTS: Four studies with a total of 452 patients met the inclusion criteria. The baseline characteristics of patients were similar across all studies. Overall, patients receiving diuretics had a significant 24 hours reduction in pro-B-type natriuretic peptide (standard mean difference of -41.97; 95% CI -65.79 to -18.15), and PASP (standard mean difference of -5.96; 95% CI -8.06 to -3.86). This group had significantly higher creatinine levels (standard mean difference of 7.74; 95% CI 5.04 to 10.45). The quality of the studies was heterogeneous; two had a low risk of bias, and the other two had a high risk of bias. CONCLUSIONS: Very few studies have compared the efficacy and safety of diuretics and fluid expansion in normotensive patients with acute PE with RV failure. Overall, furosemide appears to reduce RV dysfunction in this subset of patients compared with fluid expansion. Further research is required to confirm these findings.

Effectiveness of undergraduate medical students training on LGBTQIA + people health: a systematic review and meta-analysis.

BACKGROUND: Adequacy of learning models and their ability to engage students and match session's objectives are critical factors in achieving the desired outcome. In this systematic review and meta-analysis, we assess the methodological approach, content, and effectiveness of training initiatives addressing medical students' knowledge, attitudes, confidence and discrimination perception towards LGBTQIA + people. METHOD: PubMed, Web of Science, Medline and Scopus were searched to identify published studies, from 2013 to 2023, on effectiveness of training initiatives addressing medical students' knowledge, attitudes, confidence and discrimination perception towards LGBTQIA + people. The risk of bias of the selected studies was assessed by the Medical Education Research Study Quality Instrument. Overall effect sizes were calculated using a Mantel-Haenszel method, fixed effect meta-analyses. RESULTS: A total of 22 studies were included, representing 2,164 medical students. The interventions were highly diverse and included seminars, lectures, videos, real-case discussions, roleplay, and group discussions with people from the LGBTQIA + community. After the interventions, there was a significant improvement in self-confidence and comfort interacting with patients and in the understanding of the unique and specific health concerns experienced by LGBTQIA + patients. CONCLUSION: Our findings indicated that the outcomes of interventions training actions for medical students that promote knowledge and equity regarding LGBTQIA + people, regardless of their scope, methodology and duration, result in a considerable increase in students' self-confidence and comfort interacting with LGBTQIA + patients, highlight the need for more actions and programs in this area promoting a more inclusive society and greater equity.

Predictive Value for Increased Red Blood Cell Distribution Width in Unprovoked Acute Venous Thromboembolism at the Emergency Department.

Acute venous thromboembolism (VTE) is a common worldwide disease admitted to emergency departments (ED), usually presenting as pulmonary embolism or lower limb deep vein thrombosis (DVT). Due to the lack of typical clinical and biomarker diagnostic features of unprovoked VTE, early identification is challenging and has direct consequences on correct treatment delay. Longitudinal, prospective, observational study. Patients admitted to ED with a suspicion of unprovoked acute VTE between October 2020 and January 2021 were included. Clinical and laboratorial variables were compared between VTE positive and negative diagnoses. Red cell distribution width (RDW) cut point was determinate through a receiver operating characteristic analysis. RDW accuracy, sensitivity, and specificity were calculated. Fifty-eight patients were analyzed. And 82.8% of suspected patients with VTE were diagnosed with an acute thrombotic event confirmed by imaging examination. In patients with VTE, RDW at admission in ED was higher than with other diagnosis, respectively, 14.3% (13.2-15.1) and 13.5% (13.0-13.8). Platelet count was the only additional characteristic that revealed difference between the 2 groups (264×109/L for VTE and 209×109/L for non-VTE). Logistic regression models showed good discriminatory values for RDW≥14%, with an area under the curve (AUC) = 0.685 (95% confidence interval, 0.535-0.834). These findings were more pronounced in isolated DVT, with a sensitivity of 76.9%, specificity 100%, and accuracy 85.7%. Our study demonstrated a significant association between an early high RDW and the diagnosis of acute unprovoked DVT. RDW ≥ 14% has an independent predictor of unprovoked VTE in adult patients.

COVID-19 fatality rates in hospitalized patients: systematic review and meta-analysis.

BACKGROUND: Coronavirus disease (COVID-19) is an infectious disease caused by a newly discovered coronavirus. Although general and local public health report deathly cases, case fatality rates are still largely unknown. Thus, we sought to evaluate the mortality of COVID-19. METHODS: We searched PubMed and EMBASE databases for articles evaluating the clinical characteristics of COVID-19 patients that included clinical outcomes, between December 2020 and 24 April 2020. Two authors performed an independent selection using predefined terms of search. RESULTS: We retrieved 33 studies with a total of 13,398 patients with COVID-19 diagnosis. The mortality rate of the COVID-19 patients was 17.1% (95% CI 12.7; 22.7, I2 = 96.9%). For general patients admitted to the hospital (excluding critical care-only studies) the mortality rate of the COVID-19 was 11.5% (95% CI 7.7; 16.9, I2 = 96.7%). Among critical illness studies (n = 7) we found a 40.5% mortality (95% CI 31.2; 50.6, I2 = 91.8%). CONCLUSION: High COVID-19 mortality among general admitted patients and critical care cases should guide resources allocations and economic burden calculations during the pandemics.

Diagnostic Role of Mean-Platelet Volume in Acute Pulmonary Embolism: A Meta-analysis and Systematic Review.

BACKGROUND: Acute pulmonary embolism (PE) is the third most fatal cardiovascular disease. PE is frequently misdiagnosed due to its clinical presentation's heterogeneity and the inexistence of biomarkers for its immediate diagnosis. Mean platelet volume (MPV) has shown a potential role as a biomarker in acute PE. In this analysis, we aimed to systematically compare the MPV in patients with and without definite diagnosis of PE, in emergency departments. METHODS: Embase, PubMed and Medline were searched for relevant publications, in English. The main inclusion criteria were studies which compared MPV in patients with acute PEA versus a control group. RESULTS: Thirteen studies consisting of a total number of 2428 participants were included. Of the participants included, 1316 were patients with confirmed acute PE, and 1112 were assigned to the control group. MPV was significantly higher in patients with acute PE than in controls (RR: 0.84, 95% CI: 0.76 - 0.92; P < .00001). There was a significant heterogeneity in the data. CONCLUSIONS: This analysis showed higher MPV to be associated with acute PE immediate diagnosis. These data show promise for the use of MPV as a readily available biomarker for the diagnosis of acute PE at the emergency department.