Comparison between Colistin and Polymyxin B in the Treatment of Bloodstream Infections Caused by Carbapenem-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii-calcoaceticus Complex.

Polymyxins are still widely used for the treatment of carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa bloodstream infections (BSIs). This study seeks to evaluate the impact of polymyxin B versus colistin on mortality and nephrotoxicity in BSI caused by these bacteria. We conducted a retrospective cohort study from 2014 to 2021 in Porto Alegre, Brazil. We included patients aged ≥18 years and excluded patients with polymicrobial infection or treatment for ≤48 h. The 30-day mortality was the primary outcome evaluated through Cox regression. We included 259 patients with BSI episodes: 78.8% caused by A. baumannii and 21.2% caused by P. aeruginosa. Polymyxin B did not impact mortality compared to colistin (adjusted hazard ratio (aHR), 0.82; 95% confidence interval (CI), 0.52-1.30; p = 0.40 (when adjusted for COVID-19 comorbidity, p = 0.05), Pitt bacteremia score, p < 0.01; Charlson comorbidity index, p < 0.001; time to start active antimicrobial therapy, p = 0.02). Results were maintained in the subgroups of BSI caused by A. baumannii (aHR, 0.92; 95% CI, 0.55-1.54; p = 0.74), P. aeruginosa (aHR, 0.47; 95% CI, 0.17-1.32; p = 0.15) and critical care patients (aHR, 0.77; 95% CI, 0.47-1.26; p = 0.30). Treatment with polymyxin B or colistin did not impact 30-day mortality in patients with carbapenem-resistant A. baumannii or P. aeruginosa BSI.

Antimicrobial Therapy Duration for Bloodstream Infections Caused by Pseudomonas aeruginosa or Acinetobacter baumannii-calcoaceticus complex: A Retrospective Cohort Study.

BACKGROUND: Ideal therapy duration for Pseudomonas aeruginosa or Acinetobacter baumannii-calcoaceticus complex (ABC) bloodstream infections (BSI) is not defined, especially in the context of carbapenem resistance. In this study, we compared short- (≤7 days) and long-term (>7 days) antimicrobial therapy duration for these infections. METHODS: We performed a retrospective cohort study in two tertiary-care hospitals in Porto Alegre, Brazil, from 2013 to 2019. Eligible patients aged ≥18 years were included and excluded for the following criteria: polymicrobial infections, treatment with non-susceptible antibiotics, complicated infections, or early mortality (<8 days of active antimicrobial therapy). The 30-day mortality risk was evaluated using a Cox regression model. RESULTS: We included 237 BSI episodes, 51.5% caused by ABC and 48.5% by Pseudomonas aeruginosa. Short-term therapy was not associated with 30-day mortality, adjusted hazard ratio 1.01, 95% confidence interval 0.47-2.20, p = 0.98, when adjusted for Pitt score (p = 0.02), Charlson Comorbidity Index score (p < 0.01), and carbapenem resistance (p < 0.01). Among patients who survived, short-term therapy was associated with shorter hospital stay (p < 0.01). Results were maintained in the subgroups of BSI caused by carbapenem-resistant bacteria (p = 0.76), ABC (p = 0.61), and Pseudomonas aeruginosa (p = 0.39). CONCLUSIONS: Long-term therapies for non-complicated Pseudomonas aeruginosa and ABC BSI were not superior to short-term therapy for 30-day mortality.

Antiapoptotic effects of cannabidiol in an experimental model of cognitive decline induced by brain iron overload.

Iron accumulation in the brain has been recognized as a common feature of both normal aging and neurodegenerative diseases. Cognitive dysfunction has been associated to iron excess in brain regions in humans. We have previously described that iron overload leads to severe memory deficits, including spatial, recognition, and emotional memory impairments in adult rats. In the present study we investigated the effects of neonatal iron overload on proteins involved in apoptotic pathways, such as Caspase 8, Caspase 9, Caspase 3, Cytochrome c, APAF1, and PARP in the hippocampus of adult rats, in an attempt to establish a causative role of iron excess on cell death in the nervous system, leading to memory dysfunction. Cannabidiol (CBD), the main non-psychotropic component of Cannabis sativa, was examined as a potential drug to reverse iron-induced effects on the parameters analyzed. Male rats received vehicle or iron carbonyl (30 mg/kg) from the 12th to the 14th postnatal days and were treated with vehicle or CBD (10 mg/kg) for 14 days in adulthood. Iron increased Caspase 9, Cytochrome c, APAF1, Caspase 3 and cleaved PARP, without affecting cleaved Caspase 8 levels. CBD reversed iron-induced effects, recovering apoptotic proteins Caspase 9, APAF1, Caspase 3 and cleaved PARP to the levels found in controls. These results suggest that iron can trigger cell death pathways by inducing intrinsic apoptotic proteins. The reversal of iron-induced effects by CBD indicates that it has neuroprotective potential through its anti-apoptotic action.

Neoplasia de sítio primário desconhecido: abordagem diagnóstica e terapêutica / Cancer of onknown primary site: diagnostic and therapeutic approach

Introdução: As neoplasias de sítio primário desconhecido (NSPD) são responsáveis por 3-5% de todas as neoplasias malignas, definidas pela falha de identificação do sítio primário após a investigação diagnóstica. Métodos: Revisão bibliográfica da literatura entre abril e maio de 2018, em artigos de revisão, seminários e artigos originais, em inglês, dos últimos 20 anos. Resultados: A investigação diagnóstica das NSPD envolve uma extensa anamnese, exame físico, exames laboratoriais, exames de imagem, análise anatomopatológica e imuno-histoquímica da lesão metastática. Com base nessa investigação, são classificadas de acordo com critérios clínico-patológicos para melhor conduta terapêutica. Conclusão: As NSPD são um grande desafio para o clínico e oncologista, é imprescindível a investigação adequada dessas neoplasias para o melhor tratamento da doença.

Introduction: Cancer of unknown primary site (CUP) accounts for 3-5% of all malignant neoplasms, which is defined when the anatomical site of origin remains occult after detailed investigations. Methods: Review articles, seminars, and original articles in English for the last 20 years. Results: The diagnostic investigation of CUP involves an extensive anamnesis, physical examination, laboratory exams, imaging, anatomopathological and immunohistochemical analysis of the metastatic lesion. Based on this investigation, the neoplasms are classified according to clinical pathological criteria. Conclusion: CUP can be a challenge for the clinician and medical oncologist, it is essential to adequately investigate these neoplasms in order to define the best treatment approach.

Neutropenia febril: abordagem diagnóstica e terapêutica / Febrile neutropenia: diagnostic and therapeutic approach

Introdução: A neutropenia febril (NF) é uma das mais graves complicações em pacientes com câncer submetidos a quimioterapia. Estes casos exigem pronta avaliação diagnóstica e instituição de terapêutica adequada. A conduta frente a tal emergência ainda é muito discutida apesar dos avanços no tratamento. O objetivo do estudo foi revisar na literatura as medidas mais eficazes de manejo sindrômico da NF. Métodos: Este artigo é uma revisão bibliográfica realizada entre abril e maio de 2018 sobre neutropenia febril. Foi realizada pesquisa de artigos científicos de revisão, guidelines e artigos originais, dos últimos 15 anos. Resultados: O reconhecimento imediato do paciente com NF e seu adequado tratamento com início imediato de terapia empírica, conforme o risco do paciente, são definidores de qualidade do manejo desta síndrome. Conclusão: A avaliação inicial de todos os pacientes com NF deve ser ágil para que terapia empírica seja imediatamente iniciada.

Introduction: Febrile neutropenia (NF) is one of the most serious complications in cancer patients undergoing chemotherapy. These cases require prompt diagnostic evaluation and management. The objective of the study was to review the most effective aspects of NF syndromic management in the literature. Methods: This article is a bibliographical review performed between April and May of 2018 on febrile neutropenia. Research was done on review articles, seminars and original articles of the last 15 years. Results: The immediate recognition of the patient with NF and its appropriate treatment with immediate onset of empirical therapy, according to the risk of the patient, are critical and impact clinical outcomes. Conclusion: The initial assessment of all NF patients should be agile for empirical therapy to be initiated immediately.

Dual influences of early-life maternal deprivation on histone deacetylase activity and recognition memory in rats.

Exposure to stress early in life may negatively impact nervous system functioning, including increasing the proneness to learning and memory impairments later in life. Maternal deprivation, a model of early-life stress, hinders memory in adult rats and lessens brain-derived neurotrophic factor (BDNF) levels in the hippocampus in a very heterogeneous way among individuals. The main goal of the present study was to investigate the possible epigenetic modulation underlying recognition memory impairment and reduced BDNF levels in the hippocampus of adult maternally deprived rats. We also evaluated the potential ameliorating properties of the histone deacetylase (HDAC) inhibitor, sodium butyrate, on memory deficits and BDNF changes related to maternal deprivation. Maternally deprived animals were categorized as 'inferior learners' and 'superior learners' according to their performance in object recognition memory task in comparison to controls. Results indicated that HDAC activity was higher in individuals submitted to maternal deprivation with the worst cognitive performance (inferior learners). Acute administration of sodium butyrate increased histone H3 acetylation and BDNF levels, and restored recognition memory in maternally deprived animals with the worst cognitive performance. Moreover, we also showed that there is a positive correlation between BDNF levels and memory performance. Taken together, the results indicated that HDAC inhibitors could be considered as a possible therapeutic agent to improve cognitive performance in inferior learners. Further studies need to be conducted for a better comprehension of the mechanisms related to persistent alterations observed in adult life induced by early stressful circumstances and those leading to resilience.