The effect of biologic agents currently used for rheumatoid arthritis on the central nervous system of healthy rats

The aim of this study was to investigate the development of behavioral and memory disorders on healthy adult rats, after chronic, systematic administration of methotrexate and the biologic agents, Tocilizumab (anti-IL6) and Infliximab (anti-TNFa), that are used for Rheumatoid Arthritis. 35 adult male Wistar rats, 12 weeks old, were used in this study. The rats were divided into 5 groups (n=7): a control group (CTRL), which was submitted to tests without receiving any drug, a placebo group (PLC) which received normal saline (i.p.), a methotrexate group (MTX) receiving 0.25mg/kg of the drug (i.p.), an infliximab group (INFL) receiving 6mg/kg of the drug (i.p.), and a tocilizumab group (TCZ) receiving 8mg/kg of the drug (i.p.). The drug infusion was performed weekly. After 30 days of drug administration, behavioral tests were performed to assess the rats’ stress levels and memory. The performed behavioral tests were (1) the Elevated-plus maze test, (2) the Elevated-zero maze test and (3) the Olfactory social memory test. The results were analyzed using Oneway-ANOVA and Kruskal-Wallis tests through SPSS 25.0. The MTX group spent significantly less time in the open arms of the mazes, compared to the CTRL group (P<0.001) and the PLC group (p=0.05), and needed less time during the second encounter compared to the first, when assessed in the olfactory social memory test (p=0.002). The TCZ and INFL groups spent more time in the open areas of both mazes compared to PLC and MTX groups (p=0.033). Based on the results of this study, the administration of biologic agents improves stress levels and shows a potentially anxiolytic effect, without significantly affecting memory

Invasive Pulmonary Aspergillosis in Coronavirus Disease 2019 Patients Lights and Shadows in the Current Landscape

Invasive pulmonary aspergillosis (IPA) presents a known risk to critically ill patients with SARS-CoV-2; quantifying the global burden of IPA in SARS-CoV-2 is extremely challenging. The true incidence of COVID-19-associated pulmonary aspergillosis (CAPA) and the impact on mortality is difficult to define because of indiscriminate clinical signs, low culture sensitivity and specificity and variability in clinical practice between centers. While positive cultures of upper airway samples are considered indicative for the diagnosis of probable CAPA, conventional microscopic examination and qualitative culture of respiratory tract samples have quite low sensitivity and specificity. Thus, the diagnosis should be confirmed with serum and BAL GM test or positive BAL culture to mitigate the risk of overdiagnosis and over-treatment. Bronchoscopy has a limited role in these patients and should only be considered when diagnosis confirmation would significantly change clinical management. Varying diagnostic performance, availability, and time-to-results turnaround time are important limitations of currently approved biomarkers and molecular assays for the diagnosis of IA. The use of CT scans for diagnostic purposes is controversial due to practical concerns and the complex character of lesions presented in SARS-CoV-2 patients. The key objective of management is to improve survival by avoiding misdiagnosis and by initiating early, targeted antifungal treatment. The main factors that should be considered upon selection of treatment options include the severity of the infection, concomitant renal or hepatic injury, possible drug interactions, requirement for therapeutic drug monitoring, and cost of therapy. The optimal duration of antifungal therapy for CAPA is still under debate