ABC2-SPH risk score for in-hospital mortality in COVID-19 patients: development, external validation and comparison with other available scores.

OBJECTIVES: The majority of available scores to assess mortality risk of coronavirus disease 2019 (COVID-19) patients in the emergency department have high risk of bias. Therefore, this cohort aimed to develop and validate a score at hospital admission for predicting in-hospital mortality in COVID-19 patients and to compare this score with other existing ones. METHODS: Consecutive patients (≥ 18 years) with confirmed COVID-19 admitted to the participating hospitals were included. Logistic regression analysis was performed to develop a prediction model for in-hospital mortality, based on the 3978 patients admitted between March-July, 2020. The model was validated in the 1054 patients admitted during August-September, as well as in an external cohort of 474 Spanish patients. RESULTS: Median (25-75th percentile) age of the model-derivation cohort was 60 (48-72) years, and in-hospital mortality was 20.3%. The validation cohorts had similar age distribution and in-hospital mortality. Seven significant variables were included in the risk score: age, blood urea nitrogen, number of comorbidities, C-reactive protein, SpO2/FiO2 ratio, platelet count, and heart rate. The model had high discriminatory value (AUROC 0.844, 95% CI 0.829-0.859), which was confirmed in the Brazilian (0.859 [95% CI 0.833-0.885]) and Spanish (0.894 [95% CI 0.870-0.919]) validation cohorts, and displayed better discrimination ability than other existing scores. It is implemented in a freely available online risk calculator (https://abc2sph.com/). CONCLUSIONS: An easy-to-use rapid scoring system based on characteristics of COVID-19 patients commonly available at hospital presentation was designed and validated for early stratification of in-hospital mortality risk of patients with COVID-19.

Identification of immune biomarkers related to disease progression and treatment efficacy in human visceral leishmaniasis.

Visceral leishmaniasis (VL) is a potentially fatal disease, in which the treatment based on chemotherapy is considered toxic. The cure of disease is associated with the life-long Th1-type immunity against the infection. The Th1-related cytokines production by peripheral blood mononuclear cells (PBMCs) seems to be crucial for host control of parasite load and clinical cure. In the current study, we used five proteins (IgE-dependent histamine-releasing factor [HRF], LiHyD, LiHyV, LiHyT and LiHyp6) recently shown to be antigenic and/or immunogenic in the canine VL, aiming to evaluate the antigen-specific antibody levels and cytokine production in PBMCs culture supernatants collected from VL patients before and after anti-VL treatment. In the results, when PBMCs were exposed to rHRF, rLiHyD and rLiHyT, higher IFN-γ and lower IL-10 levels were observed in all patients that were treated and clinically cured. Analysis of specific antibody subclasses was in line with in vitro cellular response, since a higher IgG2 production was found in the treated and cured patients, when compared to the IgG1 subclass levels. In addition, evaluating the diagnostic efficacy of the recombinant molecules, the rHRF, rLiHyD and rLiHyT proteins showed the best results in the serology assays to identify all VL patients, as well as these antigens were not recognized by antibodies in sera from non-infected subjects or those with leishmaniasis-related diseases. Our results corroborate the view that clinical cure of VL is associated with a sustained Th1-related response, and indicate the potential use of rHRF, rLiHyD and rLiHyT as immune biomarkers of VL treatment.

Modifications in basal and stress-induced hypothalamic AMP-activated protein kinase (AMPK) activity in rats chronically treated with an angiotensin II receptor blocker.

5' adenosine monophosphate-activated protein kinase (AMPK) plays a prominent role as a metabolic stress sensor. The role of hypothalamic AMPK in response to restraint and surgical stress has not been previously investigated. It has been recently suggested that the renin-angiotensin system, in addition to its role in stress regulation, may play a significant role in regulating metabolic pathways including the regulation of the AMPK system. This study was thus aimed to evaluate the effects of candesartan, an angiotensin II AT1 receptor blocker drug, on hypothalamic AMPK activity under basal conditions and after restraint in conscious rats or after surgical stress under general anesthesia. Male Wistar rats were treated with 5 mg/kg/day candesartan in the drinking water for 2 weeks. The hypothalamic AMPK activity was determined under basal and stress conditions, using a kinase activity assay. Chronic administration of candesartan significantly increased hypothalamic AMPK activity. Hypothalamic AMPK activity was also increased by restraint stress whereas no change was observed during surgical stress under anesthesia. The high levels of hypothalamic AMPK activation observed in candesartan-treated rats were not changed by restraint stress but were reduced to control levels by anesthesia and surgery. In conclusion, chronic candesartan treatment and restraint stress in conscious rats stimulate the hypothalamic AMPK activity, whereas surgical stress under anesthesia inhibits pathways regulating the AMPK activity even in candesartan-treated rats.

Metabolic long-term follow-up of functioning simultaneous pancreas-kidney transplantation versus pancreas transplantation alone: insights and limitations.

BACKGROUND: Pancreas transplantation involves a set of procedures that, in some cases, lead to different complications and outcomes. The aim of this study was to analyze the long-term effects of pancreas transplantation regarding carbohydrate and lipid metabolism parameters to determine differences between simultaneous pancreas-kidney (SPK) transplantation and pancreas transplantation alone (PTA). METHODS: Sixty-four patients (46 SPK and 18 PTA), with an immunosuppression protocol based on tacrolimus plus mycophenolate mofetil and prednisone, were evaluated for at least 1 year after transplantation. No patient made use of any hypoglycemic or hypolipidemic drugs. Comparisons were performed between SPK and PTA patients using the chi-square test, Fischer's exact test, and unpaired Student's t test, as appropriate. RESULTS: Patients were 39.8+/-9.3 years old, predominantly male (60.9%), with a mean follow-up of 25.4+/-10.4 months after transplantation. The PTA group exhibited worse renal function and higher tacrolimus levels than the SPK group. Fasting glucose, 2 hr plasma glucose after overload, C-peptide, and HbA1C were within the normal range, with no statistically significant differences between the PTA and SPK groups. Insulin (INS) and the homeostasis model assessment of INS resistance index were above the normal range in both the groups. Lipids were also similar between groups. CONCLUSIONS: The majority of patients with long-term functioning pancreas transplant achieved good glucose control without use of exogenous INS or oral antidiabetic drugs, although they were hyperinsulinemic. There were no significant differences concerning glucose and lipid parameters between the SPK and PTA groups, even though the PTA patients exhibited higher tacrolimus levels and worse renal function.