Rapid identification,fluconazole and micafungin susceptibility testing of Candida species from blood culture by a short incubation method.

This study aimed to develop and validate a rapid method for identification by MALDI-TOF system and determination of the susceptibility to Fluconazole and Micafungin by broth microdilution among Candidaspecies causing bloodstream infections. Subcultures from blood culture bottles were incubated for 5 hours (+/- 1h) and used to perform the tests, so that the turnaround time of rapid identification and susceptibility profile was about 5 and 24 hours, respectively. The rapid identification showed agreement of 92.05 %. Regarding the rapid broth microdilution for Fluconazole and Micafungin, the agreement was 97.06 % (p<0.001) and 100 % (p<0.001), and the Kappa coefficient was 0.91 (p<0.001) and 1.0 (p<0.001), respectively. To conclude, both rapid methods showed to be reproducible, inexpensive, easy to perform and time-saving. Thus, these methodologies could be useful to guide and adjust empirical antifungal therapy.

Relationship between pruritus and sleep in participants with primary biliary cholangitis in the Phase 2b GLIMMER trial.

BACKGROUND: Cholestatic pruritus and fatigue are debilitating conditions associated with primary biliary cholangitis (PBC) and can significantly impact patients' quality of life. Pruritus in PBC often worsens at night and patients frequently report sleep disturbance, which contributes to cognitive symptoms and fatigue. Linerixibat is an ileal bile acid transporter inhibitor in clinical development for the treatment of pruritus associated with PBC and was recently assessed versus placebo in the Phase 2b GLIMMER trial. This post-hoc analysis assesses the relationship between pruritus severity and sleep disturbance in participants of GLIMMER regardless of treatment group. METHODS: GLIMMER (NCT02966834), a multicenter, double-blind, randomized, placebo-controlled trial, recruited 147 patients with PBC and moderate-to-severe pruritus. Following 4 weeks single-blind placebo, patients (randomized 3:1) received linerixibat or placebo for 12 weeks (to Week 16). Participants graded their itch (twice daily) and its interference with sleep (once daily) in an electronic diary using a 0-10 numerical rating scale (NRS). Weekly and monthly itch scores were calculated as the mean of the worst daily itch score over the respective time period. At study visits, participants completed the 5-D itch scale and the PBC-40 quality of life questionnaire, both of which contain an item specific to itch-related sleep disturbance. The impact of pruritus on sleep was assessed post hoc through correlations between the changes in NRS, 5-D itch, and PBC-40. RESULTS: Strong correlations were found between change from baseline in weekly itch and sleep NRS scores (r = 0.88 [95% confidence interval (CI): 0.83; 0.91]) at the end of treatment (Week 16), as well as in monthly itch and sleep NRS scores (r = 0.84 [95% CI: 0.80; 0.87]). Patients with improved weekly pruritus score severity category demonstrated reduced perceived sleep interference on average. Itch responders (≥2-point improvement in weekly itch score from baseline) displayed larger improvements in weekly sleep NRS score, 5-D itch, and PBC-40 sleep items, than itch non-responders (<2-point improvement). CONCLUSIONS: A strong correlation exists between changes in pruritus severity and sleep interference in patients with PBC; pruritus reduction could generate concomitant improvement in sleep.

Molecular and clinicopathologic characteristics of CNS embryonal tumors with BRD4::LEUTX fusion.

Central nervous system (CNS) embryonal tumors are a heterogeneous group of high-grade malignancies, and the increasing clinical use of methylation profiling and next-generation sequencing has led to the identification of molecularly distinct subtypes. One proposed tumor type, CNS tumor with BRD4::LEUTX fusion, has been described. As only a few CNS tumors with BRD4::LEUTX fusions have been described, we herein characterize a cohort of 9 such cases (4 new, 5 previously published) to further describe their clinicopathologic and molecular features. We demonstrate that CNS embryonal tumor with BRD4::LEUTX fusion comprises a well-defined methylation class/cluster. We find that patients are young (4 years or younger), with large tumors at variable locations, and frequently with evidence of leptomeningeal/cerebrospinal fluid (CSF) dissemination. Histologically, tumors were highly cellular with high-grade embryonal features. Immunohistochemically, 5/5 cases showed synaptophysin and 4/5 showed OLIG2 expression, thus overlapping with CNS neuroblastoma, FOXR2-activated. DNA copy number profiles were generally flat; however, two tumors had chromosome 1q gains. No recurring genomic changes, besides the presence of the fusion, were found. The LEUTX portion of the fusion transcript was constant in all cases assessed, while the BRD4 portion varied but included a domain with proto-oncogenic activity in all cases. Two patients with clinical follow up available had tumors with excellent response to chemotherapy. Two of our patients were alive without evidence of recurrence or progression after gross total resection and chemotherapy at 16 and 33 months. One patient relapsed, and the last of our four patients died of disease one month after diagnosis. Overall, this case series provides additional evidence for this as a distinct tumor type defined by the presence of a specific fusion as well as a distinct DNA methylation signature. Studies on larger series are required to further characterize these tumors.

Evaluation of clinical and microbiological factors related to mortality in patients with Gram-negative bacterial infections treated with ceftazidime-avibactam: A prospective multicentric cohort study.

OBJECTIVES: This study aimed to evaluate the clinical and microbiological risk factors associated with mortality in patients treated with ceftazidime-avibactam for carbapenem-resistant Gram-negative bacterial infections. METHODS: This multicentric prospective cohort study included hospitalized adult patients with a microbiologically confirmed infection treated with ceftazidime-avibactam for ≥48 hours. The clinical and microbiological risk factors for 30-day mortality were evaluated using a Cox regression model. RESULTS: Of the 193 patients evaluated from the five tertiary hospitals, 127 were included in the study. Thirty-five patients (27.6%) died within 30 days. Infections with AmpC beta-lactamase-carrying bacteria were independently related to 30-day mortality (adjusted hazard ratio [aHR] 2.49, 95% confidence interval [CI] 1.28-4.84, P < 0.01) after adjusting for time from infection to antimicrobial prescription (P = 0.04). Further, these bacterial infections were also related to higher in-hospital mortality (aHR 2.17, 95% CI 1.24-3.78, P < 0.01). Only one patient developed resistance to ceftazidime-avibactam during treatment. CONCLUSIONS: Treatment with ceftazidime-avibactam had worse clinical outcomes in patients with infections with bacteria with chromosomally encoded AmpC beta-lactamase. However, these findings should be confirmed in future studies.

Susceptibility evaluation of novel beta-lactam/beta-lactamase inhibitor combinations against carbapenem-resistant Klebsiella pneumoniae from bloodstream infections in hospitalized patients in Brazil.

INTRODUCTION: Novel beta-lactam/beta-lactamase inhibitor (BIBLI) combinations are commercially available and have been used for treating carbapenem-resistant Klebsiella pneumoniae (CRKP) infections. Continuous surveillance of susceptibility profiles and resistance mechanism identification are necessary to monitor the evolution of resistance within these agents. OBJECTIVE: The purpose of this study was to evaluate the susceptibility rates of ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam in CRKP isolated from patients with bloodstream infections who underwent screening for a randomized clinical trial in Brazil. METHODS: Minimum inhibitory concentrations (MICs) were determined for meropenem, ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam using the gradient diffusion strip method. Carbapenemase genes were detected by multiplex real-time polymerase chain reaction. Klebsiella pneumoniae carbapenemase (KPC)-producing isolates showing resistance to any BLBLI and New Delhi Metallo-beta-lactamase (NDM)-producing isolates with susceptibility to any BLBLI isolates were further submitted for whole-genome sequencing. RESULTS: From a total of 69 CRKP isolates, 39 were positive for blaKPC, 19 for blaNDM and 11 for blaKPC and blaNDM. KPC-producing isolates demonstrated susceptibility rates above 94 % for all BLBLIs. Two isolates with resistance to meropenem/vaborbactam demonstrated a Gly and Asp duplication at the porin OmpK36 as well as a truncated OmpK35. All NDM-producing isolates, including KPC and NDM coproducers, demonstrated susceptibility rates to ceftazidime/avibactam, imipenem/relebactam and meropenem/vaborbactam of 0 %, 9.1-21.1 % and 9.1-26.3 %, respectively. Five NDM-producing isolates that presented susceptibility to BLBLIs also had porin alterations CONCLUSIONS: This study showed that, although high susceptibility rates to BLBLIs were found, KPC-2 isolates were able to demonstrate resistance probably as a result of porin mutations. Additionally, NDM-1 isolates showed susceptibility to BLBLIs in vitro.

Hydrogels based on galactomannan and κ-carrageenan containing immobilized biomolecules for in vivo thermal-burn wound treatment.

Hydrogels based on natural polysaccharides have demonstrated efficacy in epithelial recovery from cutaneous burn wounds. Here, we prepared a double-network hydrogel consisting of galactomannan (from Cassia grandis seeds) and κ-carrageenan (commercially sourced), cross-linked with CaCl2, as a matrix for immobilizing lactoferrin and/or Cramoll, aiming at its applicability as dressings for second-degree burn wounds. The formulations obtained [H - hydrogel, HL - hydrogel + lactoferrin, HC - hydrogel + Cramoll and HLC - hydrogel + lactoferrin + Cramoll] were analyzed rheologically as well as in terms of their stability (pH, color, microbial contamination) for 90 days. The burn was created with an aluminum bar (97 ± 3 °C) in the dorsal region of Wistar rats and subsequently treated with hydrogels (H, HL, HC, HLC) and control saline solution (S). The burn was monitored for 3, 7 and 14 days to evaluate the efficacy of the hydrogels in promoting wound healing. The hydrogels did not reveal significant pH or microbiological changes; there was an increase in brightness and a reduction in opacity for H. The rheological analysis confirmed the gel-like viscoelastic signature of the systems without substantial modification of the basic rheological characteristics, however HLC proved to be more rigid, due to rheological synergy when combining protein biomolecules. Macroscopic analyses confirmed centripetal healing with wound contraction: S < H < HC < HL < HLC. Histopathological analyses showed that hydrogel-treated groups reduced inflammation, tissue necrosis and fibrosis, while promoting re-epithelialization with focal acanthosis, especially in HLC due to a positive synergistic effect, indicating its potential as a promising therapy in the repair of burns.

Rapid bacterial identification by MALDI-TOF MS directly from blood cultures and rapid susceptibility testing: A simple approach to reduce the turnaround time of blood cultures

Abstract Antimicrobial treatment of patients with bloodstream infections (BSI) is time-sensitive. In an era of increasing antimicrobial resistance, rapid detection and identification of bacteria with antimicrobial susceptibility are critical for targeted therapy early in the disease course. This study describes the performance of a rapid method for identifying and testing antimicrobial susceptibility of Gram-negative bacteria performed directly from blood culture bottles in a routine microbiology laboratory. A total of 284, 120, and 24 samples were analyzed by rapid identification (Rid), rapid susceptibility testing (RAST), and rapid broth microdilution for polymyxin B (rMIC), respectively, and compared with standard methods. Our protocol was able to identify 93% of isolates at the species level using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). We obtained 100% agreement for RAST compared to the standard method and 96% agreement for rMIC. Our protocol has proven to be an excellent tool for rapid identification of Gram-negative bacilli causing BSIs. It can also be used in microbiology laboratory routine along with RAST and faster polymyxin microdilution, especially for carbapenemase-producing bacteria, allowing for rapid, simple, accurate, and cost-effective diagnosis.

A (DES) INTEGRALIDADE DAS PRÁTICAS DE ATENÇÃO EM SAÚDE MENTAL NUMA EMERGÊNCIA DE UM HOSPITAL "QUASE GERAL" / THE (DIS) INTEGRALITY OF MENTAL HEALTH CARE PRACTICES IN AN EMERGENCY OF AN "ALMOST GENERAL" HOSPITAL

A política de saúde mental brasileira aponta o hospital geral como parte integrante da rede de serviços substitutivos ao hospital psiquiátrico. É preconizado que os serviços substitutivos levem em consideração o acolhimento, o vínculo e a integralidade na prestação do cuidado. O objetivo deste artigo constitui-se em analisar as práticas assistenciais as pessoas com transtornos mentais em uma emergência de um hospital geral e os seus efeitos para integralidade do cuidado. Materiais e métodos: Pesquisa descritiva de abordagem qualitativa. O cenário foi o serviço de emergência de um hospital geral, localizado na zona oeste do município do Rio de Janeiro. Os dados foram obtidos por meio de entrevista semiestruturada e observação participante. Resultados: O espaço físico da emergência pouco favorecia o desenvolvimento de uma atenção acolhedora, resolutiva e humanizada. As práticas assistenciais eram predominantemente pautadas pelo modo asilar. Noções de acolhimento, vínculo e integralidade faziam parte do discurso mas ainda não se materializam nas práticas assistenciais. Discussão: O estigma atribuído à doença mental constituiu-se empecilho à adoção de práticas acolhedoras. Conclusão: A fim de possibilitar que hospital geral adote práticas integrais e que se constitua como parte da rede de serviços substitutivos em saúde mental é necessário investir em novos arranjos institucionais que coloquem o usuário no centro dos modos de produção de atos de saúde; investir na dimensão cuidadora da qualificação dos profissionais de saúde.

The current Brazilian mental health policy points to the general hospital as an integral part of the network of substitutive services to the psychiatric hospital. It is recommended that substitute services take into account, among other premises, the user embracement, bonding and integrality in the provision of care.The purpose of this article is to analyze the care practices of people with mental disorders in a general hospital emergency and their effects for integral care.Materials and methods: Descriptive research of qualitative approach. The scenario of the study was the emergency service of a general hospital, located in the western part of the municipality of Rio de Janeiro. Data were obtained through a semi-structured interview and participant observation.Results: The physical space of the emergency did not favor the development of a warm, resolutive and humanized attention. The care practices were predominantly based on the asylum mode. Notions the user embracement, bond and integrality were part of the discourse, but they did not materialize in the assistance practices. Discussion: The stigma attributed to mental illness was perceived as hindering the adoption the user embracement practices. Conclusion: In order to make it possible for a general hospital to adopt comprehensive and to be part of the network of substitutive services in mental health, it is necessary to invest in new institution arrangements that place the user at the center of the modes of production of health acts.

Refletindo sobre os centros de atençãopsicossocial / Reflating on psychosocial attention centers

Introdução: O processo de Reforma Psiquiátrica, em curso no Brasil, aponta para a construção e incorporação de novas práticasem saúde mental, como a implantação dos Centros de AtençãoPsicossocial (CAPS). O Ministério da Saúdeincorporou esse dispositivo como a principal estratégia de enfrentamento do modelo assistencial tradicional. Objetivos: Este artigo tem como objetivo refletir sobre a importância dos CAPS como projeto político-social na produção de novos sentidos para a doença mental. Metodologia: Trata-se de um estudo de revisão de literatura de abordagem qualitativa. Resultados: Percebeu-se que a dificuldade de inserçãodesses serviços, de maneira mais ampla, no territórioconstitui-se empecilho para a promoção de novos sentidos para a loucura. Como também, que o projeto de promover uma transformação cultural acerca de loucura ainda é incipiente. Conclusão: Faz-se necessário que os CAPS se inscrevam de maneira mais ampla no território, aumentando sua projeção frente às políticas sociais.

Background: The Psychiatric Reform process currently underway in Brazil points to the construction and adoption of new mental health practices, among which is the implementation of Psychosocial Attention Centers (PAC). The Brazilian Health Ministry adopted this device as the main strategy for coping with the traditional welfare model. Objectives: This article aims to perform reflection on the importance of psychosocial, political and social project in the production of new directions for mental illness. Methodology: This is a study of literature review of qualitative approach. Results: It was felt that the difficulty of inserting these services more widely in the territory constitutes a hindrance to the promotion of new directions for the madness. Furthermore, the project of promoting a cultural change about madness is still incipient. Conclusion: It is necessary that the PAC expand more broadly into the territory, increasing its projection in the face of social policies.

Introducción: El proceso de la Reforma Psiquiátrica en curso en Brasil apunta a la construcción e incorporación de nuevas prácticas de salud mental, como la implementación de los Centros de Atención Psicosociales (CAPS). El Ministerio de Sanidad de Brasil incorporó este dispositivo como la principal estrategia para hacer frente al tradicional modelo asistencial. Objetivos: Este artículo pretende reflexionar sobre la importancia de los CAPS como proeyecto político y social en la producción de nuevos sentidos para la enfermedad mental. Metodología: Se trata de un estudio de revisión de la literatura de abordaje cualitativo. Resultados: Se observó que la dificultad de inserción de estos servicios, más ampliamente en el territorio, constituye un factor que impide la promoción de nuevos sentidos a la locura. Además, el proyecto de promover una transformación cultural en relación con la locura es todavía incipiente. Conclusión: Es necesario que los CAPS se registren de manera más amplia en el territorio, incrementando su proyección frente las políticas sociales.