Characteristics, mortality, associated variables with death, and therapeutic response among HIV-positive, solid organ transplant (SOT), and non-HIV-positive/non-transplant (NHNT) patients with cryptococcosis: First multicenter cohort study in Brazil.

Cryptococcosis is traditionally associated with immunocompromised patients but is increasingly being identified in those without the human immunodeficiency virus (HIV) or other immunocompetent individuals. We aim to describe the characteristics, mortality, and associated variables with death among hospitalized patients with cryptococcosis in Brazil. This is the first multicenter retrospective cohort study conducted in seven public tertiary Brazilian hospitals. A total of 384 patients were included; the median age was 39 years and 283 (73.7%) were men. In all, 304 HIV-positive were hosts (79.2%), 16 (4.2%) solid organ transplant (SOT), and 64 (16.7%) non-HIV-positive/non-transplant (NHNT). Central nervous system (CNS) cryptococcosis had a significantly higher number across disease categories, with 313 cases (81.5%). A total of 271 (70.6%) patients were discharged and 113 (29.4%) died during hospitalization. In-hospital mortality among HIV-positive, SOT, and NHNT was 30.3% (92/304), 12.5% (2/16), and 29.7% (19/64), respectively. Induction therapy with conventional amphotericin B (AMB) mainly in combination with fluconazole (234; 84.2%) was the most used. Only 80 (22.3%) patients received an AMB lipid formulation: liposomal (n = 35) and lipid complex (n = 45). Most patients who died belong to the CNS cryptococcosis category (83/113; 73.4%) when compared with the others (P = .017). Multivariate analysis showed that age and disseminated cryptococcosis had a higher risk of death (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.05; P = .008 and OR, 1.84; 95% CI, 1.01-3.53; P = .048, respectively). Understanding the epidemiology of cryptococcosis in our settings will help to recognize the burden and causes of mortality and identify strategies to improve this scenario.

This multicenter cohort study included 384 hospitalized individuals with cryptococcosis in Brazil. Most individuals were men (74%), HIV-positive (79%), had central nervous system involvement (82%), and received conventional amphotericin plus fluconazole (84%). In-hospital mortality was high (29%).

Sertraline repositioning: an overview of its potential use as a chemotherapeutic agent after four decades of tumor reversal studies.

Sertraline hydrochloride is a first-line antidepressant with potential antineoplastic properties because of its structural similarity with other drugs capable to inhibit the translation-controlled tumor protein (TCTP), a biomolecule involved in cell proliferation. Recent studies suggest it could be repositioned for cancer treatment. In this review, we systematically map the findings that repurpose sertraline as an antitumoral agent, including the mechanisms of action that support this hypotesis. From experimental in vivo and in vitro tumor models of thirteen different types of neoplasms, three mechanisms of action are proposed: apoptosis, autophagy, and drug synergism. The antidepressant is able to inhibit TCTP, modulate chemotherapeutical resistance and exhibit proper cytotoxicity, resulting in reduced cell counting (in vitro) and shrunken tumor masses (in vivo). A mathematical equation determined possible doses to be used in human beings, supporting that sertraline could be explored in clinical trials as a TCTP-inhibitor.

Chemotherapy in focus: A meta-analysis confronts immunotherapy in the treatment of advanced melanoma.

This study aimed to analyze the efficacy of the monoclonal antibodies ipilimumab, nivolumab, and pembrolizumab when compared with conventional chemotherapy in the treatment of advanced melanoma. Three authors made the search independently and five articles matched the eligibility criteria. A fourth expert confirmed their quality (κ = 1). The meta-analysis for overall survival and 12-month overall survival was impaired due to remarkably high heterogeneity (I2 = 91 % and 86 %, respectively). However, chemotherapy showed benefits on 24-months overall survival (RR = 1.60; IC95 %: 1.29, 1.98; p < 0.0001). The interruption by toxicity outcome showed no significant differences between therapies. Some studies used monoclonal antibodies in monotherapy or in combination and some groups of participants showed heterogeneity, which made the analysis difficult. Given the exorbitant costs of monoclonal antibodies in low and middle-income countries, the evidence of its benefits is limited when considering the replacement of conventional therapy with immunotherapy in public health systems.