Biomarkers as predictors of mortality in critically ill obese patients with COVID-19 at high altitude.

BACKGROUND: Obesity is a common chronic comorbidity of patients with COVID-19, that has been associated with disease severity and mortality. COVID-19 at high altitude seems to be associated with increased rate of ICU discharge and hospital survival than at sea-level, despite higher immune levels and inflammation. The primary aim of this study was to investigate the survival rate of critically ill obese patients with COVID-19 at altitude in comparison with overweight and normal patients. Secondary aims were to assess the predictive factors for mortality, characteristics of mechanical ventilation setting, extubation rates, and analytical parameters. METHODS: This is a retrospective cohort study in critically ill patients with COVID-19 admitted to a hospital in Quito-Ecuador (2,850 m) from Apr 1, 2020, to Nov 1, 2021. Patients were cathegorized as normal weight, overweight, and obese, according to body mass index [BMI]). RESULTS: In the final analysis 340 patients were included, of whom 154 (45%) were obese, of these 35 (22.7%) were hypertensive and 25 (16.2%) were diabetic. Mortality in obese patients (31%) was lower than in the normal weight (48%) and overweight (40%) groups, but not statistically significant (p = 0.076). At multivariable analysis, in the overall population, older age (> 50 years) was independent risk factor for mortality (B = 0.93, Wald = 14.94, OR = 2.54 95%CI = 1.58-4.07, p < 0.001). Ferritin and the neutrophil/lymphocyte ratio were independent predictors of mortality in obese patients. Overweight and obese patients required more positive and-expiratory pressure compared to normal-weight patients. In obese patients, plateau pressure and mechanical power were significantly higher, whereas extubation failure was lower as compared to overweight and normal weight. CONCLUSIONS: This preliminary study suggests that BMI was not associated with mortality in critically ill patients at high altitude. Age was associated with an increase in mortality independent of the BMI. Biomarkers such as ferritin and neutrophils/lymphocytes ratio were independent predictors of mortality in obese patients with COVID-19 at high altitude.

In Silico, In Vitro, and Pharmacokinetic Studies of UBMC-4, a Potential Novel Compound for Treating against Trypanosoma cruzi.

The lack of therapeutic alternatives for the treatment of Chagas disease, a neglected disease, drives the discovery of new drugs with trypanocidal activity. Consequently, we conducted in vitro studies using UBMC-4, a potential Trypanosoma cruzi AKT-like pleckstrin homology (PH) domain inhibitory compound found using bioinformatics tools. The half effective concentration (EC50) on intracellular amastigotes was determined at 1.85 ± 1 µM showing low cytotoxicity (LC50) > 40 µM on human cell lines tested. In order to study the lethal effect caused by the compound on epimastigotes, morphological changes were assessed by scanning and transmission electron microscopy. Progressive alterations such as flagellum inactivation, cell size reduction, nuclear structure alteration, condensation of chromatin towards the nuclear periphery, vacuole formation, and mitochondrial swelling with kinetoplast integrity loss were evidenced. In addition, apoptosis-like markers in T. cruzi were assessed by flow cytometry, demonstrating that the effect of UBMC-4 on T. cruzi AKT-like kinase reduced the tolerance to nutritional stress-triggered, apoptosis-like events, including DNA fragmentation, mitochondrial damage, and loss of plasma membrane integrity. After this, UBMC-4 was formulated for oral administration and pharmacokinetics were analyzed in a mouse model. Finally, upon oral administration of 200 mg/kg in mice, we found that a UBMC-4 plasma concentration remaining in circulation beyond 24 h after administration is well described by the two-compartment model. We conclude that UBMC-4 has an effective trypanocidal activity in vitro at low concentrations and this effect is evident in T. cruzi cell structures. In mice, UBMC-4 was well absorbed and reached plasma concentrations higher than the EC50, showing features that would aid in developing a new drug to treat Chagas disease.

Chin Numbness as a Presenting Symptom of Malignancy.

Numb Chin Syndrome (NCS) is a sensory neuropathy that was first described in the early 1800s. It has various etiologies, most commonly benign local pathology. However, NCS has been documented as the primary presenting symptom of systemic malignancy, most commonly breast cancer.1 This is the case of a young male who presented to the emergency department with complaints of a numb chin and was ultimately found to have invasive neoplastic lesions in the right tonsillar and mandibular regions of the face arising from metastatic large B-cell lymphoma.

Neutrophil-to-lymphocyte ratio and mean platelet volume in the diagnosis of bacterial infections in COVID-19 patients. A preliminary analysis from Ecuador.

INTRODUCTION: Hospitalized COVID-19 patients are at risk of hospital infection. The neutrophil-to-lymphocyte ratio (NLR), lymphocyte-C-reactive protein ratio (LCR) and mean platelet volume (MPV) are established inflammation markers reflecting the systemic inflammatory response. The objective of this study was to evaluate the clinical characteristics of patients with COVID-19 and bacterial co-infections, as well as the correlation with NLR and MPV. METHODS: We assessed the role of the NLR and MPV in diagnosing bacterial infections in COVID-19 patients. The Wilcoxon test was used to compare the mean NLR and MPV between the diagnostic evaluation moments, while the Mann-Whitney test was used to compare NLR and MPV by sex and age. RESULTS: The NLR was compared three days before the culture and the day of taking the culture, observing significant differences (p=0.020). MPV three days before the culture and the day of the culture were compared, also observing significant differences (p=0.031). NLR and MPV were compared at the different evaluation times according to sex and age group, observing for the age group significant differences for the NLR three days before the culture (p=0.004). CONCLUSION: In our study, there were significant differences in NLR and MPV between the three days before culture and the day of culture. It is advisable to continue to enrol more patients in the study so that in the future, we can add results on the diagnostic accuracy of the NLR and MPV in the timely diagnosis of bacterial infection in patients with COVID-19.

Repurposing of known drugs for leishmaniasis treatment using bioinformatic predictions, in vitro validations and pharmacokinetic simulations.

Leishmaniasis is a neglected tropical disease caused by Leishmania parasites and is associated to more than 1.3 million cases annually. Some of the pharmacological options for treating the disease are pentavalent antimonials, pentamidine, miltefosine, and amphotericin B. However, all are associated with a wide range of adverse effects and contraindications, as well as resistance from the parasite. In the present study, we looked for pharmacological alternatives to treat leishmaniasis, with a focus on drug repurposing. This was done by detecting potential homologs between proteins targeted by approved drugs and proteins of the parasite. The proteins were analyzed using an interaction network, and the drugs were subjected to in vitro evaluations and pharmacokinetics simulations to compare probable plasma concentrations with the effective concentrations detected experimentally. This strategy yielded a list of 33 drugs with potential anti-Leishmania activity, and more than 80 possible protein targets in the parasite. From the drugs tested, two reported high in vitro activity (perphenazine EC50 = 1.2 µg/mL and rifabutin EC50 = 8.5 µg/mL). These results allowed us to propose these drugs as candidates for further in vivo studies and evaluations of the effectiveness on their topical forms.