Introduction Sepsis is a public health problem due to its high prevalence and mortality. Mean platelet volume (MPV), a biomarker reported in routine blood counts, has been investigated and shows promise for determining fatal outcomes in septic patients. Objective Evaluate whether the mean platelet volume (MPV) and mean platelet volume-to-platelet count (MPV/P) ratio are predictors of clinical severity and mortality in patients with sepsis. Methods A prospective population cohort of 163 patients aged 18–97 years was recruited at the Intensive Care Unit of Pablo Arturo Hospital, Quito, Ecuador from 2017–2019 and followed up for 28 days. Patients were diagnosed with sepsis based on SEPSIS-3 septic shock criteria; in which the MPV and the MPV/P ratio were measured on days 1, 2, and 3. Sequential organ failure assessment (SOFA) score and presence of septic shock assessed clinical severity. Mortality on day 28 was considered the fatal outcome. Results The average age of the patients was 61,15 years (SD 20,94) and female sex was predominant. MPV cutoff points at days 1, 2 and 3 were >9,45fL, >8,95fL and >8, 85fL; and (MPV/P) ratio >8, 18, >4, 12 y >3, 95, respectively. MPV at days 2 (9,85fL) and 3 (8,55fL) and (MPV/P) ratio at days 1 (4,42), 2 (4,21), and 3 (8,55), were predictors of clinical severity assessed by septic shock, which reached significance in the ROC curves. MPV and (MPV/P) ratio were also predictors of clinical severity determined by SOFA at days 1, 2, and 3, where higher values were observed in non-survivors reaching significance in all categories. MPV and MPV/P ratio at days 1, 2 and 3 were independent predictor factors of mortality using Cox proportional hazards model (HR 2,31; 95% CI 1,36–3,94), (HR 2,11; 95% CI 1,17–3,82), (HR 2,13; 95% CI 1,07–4,21) and (HR 2,38; 95% CI 1,38–4,12), (HR 2,15; 95% CI 1,14–4,06), (HR 4,43; 95% CI, 1,72–11,37) respectively. Conclusions MPV and the MPV/P ratio are predictors of clinical severity and mortality in sepsis. The MPV and its coefficient are indicators of the biological behavior of platelets in sepsis. They should be considered as a cost-effective and rapidly available tool that guides the treatment.
Background: American trypanosomiasis, or Chagas disease, is the result of an infection caused by the Trypanosoma cruzi parasite. The disease is endemic in Latin America, where the main clinical manifestation and cause of death of Chagas patients is cardiomyopathy. The current approved treatment for this disease is based on the use of the nitroheterocyclic compound, Benznidazole. The drug is administered in high doses and for prolonged periods, which causes serious adverse effects, eventually leading to treatment discontinuation. In addition, it has only shown efficacy in the acute phase of the disease. Benznidazole has low solubility, low permeability, low bioavailability and high toxicity in the body. These physicochemical characteristics can be improved by using dendritic structures that serve as nanocarriers. Methods: In this research, poly(propylene imine) PPI dendrimers in generations 4.0 G and 5.0 G were synthesized and characterized. We performed the synthesis by divergent approach. We encapsulated Benznidazole using the equilibrium dialysis method, and we evaluated the loading efficiency and the concentration of the released drug by high-performance liquid chromatography (HPLC). Results: Preliminary results showed a drug loading efficiency on the dendrimer of 78% and an entrapment percentage of 99.6%. The release kinetics showed a controlled and sustained release over time compared to dendrimer-free Benznidazole. Conclusions: The PPI 5.0 G - Benznidazole dendrimer system could be considered as an alternative to be evaluated in vitro and in vivo, as an alternative to conventional treatment of Chagas disease. The next stage of the experimental work consists of standardizing an infection model of H9C2 cardiomyocytes with Colombian strains of Trypanosoma cruzi, in order to evaluate the effect of the encapsulated drug on nanocarriers.
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