Bacterial microbiome changes after fecal transplantation for recurrent Clostridioides difficile infection in the Brazilian center.

Clostridioides difficile infection (CDI) poses a significant global health threat owing to its substantial morbidity and associated healthcare costs. A key challenge in controlling CDI is the risk of multiple recurrences, which can affect up to 30% of patients. In such instances, fecal microbiota transplantation (FMT) is increasingly recognized as the optimal treatment. However, few related studies have been conducted in developing countries, and the microbiota composition of Brazilian patients and its dynamic modification post-FMT remain largely unexplored. This study aimed to evaluate the changes in the bacterial gut microbiome in Brazilian patients with recurrent CDI post-FMT. Ten patients underwent FMT, and the primary and overall CDI resolution rates were 80% and 90% after the first and second FMT, respectively. FMT was associated with an early increase in Shannon's diversity, evident as soon as 1 week post-FMT and persisting for at least 25 days post-treatment. Post-treatment, the abundance of Firmicutes increased and that of Proteobacteria decreased. Specifically, the abundance of the genera Ruminococcus, Faecalibacterium, Lachnospira, and Roseburia of the Firmicutes phylum was significantly higher 1 week post-transplantation, with Ruminococcus and Faecalibacterium remaining enriched 25 days post-transplantation. This study is the first of its kind in Brazil to evaluate the microbiota of a donor and patients undergoing FMT. Our findings suggest that FMT can induce remarkable changes in the gut microbiota, characterized by an early and sustained increase in diversity lasting at least 25 days. FMT also promotes enrichment of genera such as Ruminococcus spp., Faecalibacterium spp., and Roseburia spp., essential for therapeutic success.

STRUCTURING A FECAL MICROBIOTA TRANSPLANTATION CENTER IN A UNIVERSITY HOSPITAL IN BRAZIL.

BACKGROUND: Fecal microbiota transplantation (FMT) is an important therapeutic option for recurrent or refractory Clostridioides difficile infection, being a safe and effective method. Initial results suggest that FMT also plays an important role in other conditions whose pathogenesis involves alteration of the intestinal microbiota. However, its systematized use is not widespread, especially in Brazil. In the last decade, multiple reports and several cases emerged using different protocols for FMT, without standardization of methods and with variable response rates. In Brazil, few isolated cases of FMT have been reported without the implantation of a Fecal Microbiota Transplantation Center (FMTC). OBJECTIVE: The main objective of this study is to describe the process of implanting a FMTC with a stool bank, in a Brazilian university hospital for treatment of recurrent and refractory C. difficile infection. METHODS: The center was structured within the criteria required by international organizations such as the Food and Drug Administration, the European Fecal Microbiota Transplant Group and in line with national epidemiological and regulatory aspects. RESULTS: A whole platform involved in structuring a transplant center with stool bank was established. The criteria for donor selection, processing and storage of samples, handling of recipients before and after the procedure, routes of administration, short and long-term follow-up of transplant patients were determined. Donor selection was conducted in three stages: pre-screening, clinical evaluation and laboratory screening. Most of the candidates were excluded in the first (75.4%) and second stage (72.7%). The main clinical exclusion criteria were: recent acute diarrhea, overweight (body mass index ≥25 kg/m2) and chronic gastrointestinal disorders. Four of the 134 candidates were selected after full screening, with a donor detection rate of 3%. CONCLUSION: The implantation of a transplant center, unprecedented in our country, allows the access of patients with recurrent or refractory C. difficile infection to innovative, safe treatment, with a high success rate and little available in Brazil. Proper selection of qualified donors is vital in the process of implementing a FMTC. The rigorous clinical evaluation of donors allowed the rational use of resources. A transplant center enables treatment on demand, on a larger scale, less personalized, with more security and traceability. This protocol provides subsidies for conducting FMT in emerging countries.

Estruturação de centro de transplante de microbiota fecal em hospital universitário no Brasil / Structuring a fecal microbiota transplantation center in a university hospital in brazil

ABSTRACT BACKGROUND: Fecal microbiota transplantation (FMT) is an important therapeutic option for recurrent or refractory Clostridioides difficile infection, being a safe and effective method. Initial results suggest that FMT also plays an important role in other conditions whose pathogenesis involves alteration of the intestinal microbiota. However, its systematized use is not widespread, especially in Brazil. In the last decade, multiple reports and several cases emerged using different protocols for FMT, without standardization of methods and with variable response rates. In Brazil, few isolated cases of FMT have been reported without the implantation of a Fecal Microbiota Transplantation Center (FMTC). OBJECTIVE: The main objective of this study is to describe the process of implanting a FMTC with a stool bank, in a Brazilian university hospital for treatment of recurrent and refractory C. difficile infection. METHODS: The center was structured within the criteria required by international organizations such as the Food and Drug Administration, the European Fecal Microbiota Transplant Group and in line with national epidemiological and regulatory aspects. RESULTS: A whole platform involved in structuring a transplant center with stool bank was established. The criteria for donor selection, processing and storage of samples, handling of recipients before and after the procedure, routes of administration, short and long-term follow-up of transplant patients were determined. Donor selection was conducted in three stages: pre-screening, clinical evaluation and laboratory screening. Most of the candidates were excluded in the first (75.4%) and second stage (72.7%). The main clinical exclusion criteria were: recent acute diarrhea, overweight (body mass index ≥25 kg/m2) and chronic gastrointestinal disorders. Four of the 134 candidates were selected after full screening, with a donor detection rate of 3%. CONCLUSION: The implantation of a transplant center, unprecedented in our country, allows the access of patients with recurrent or refractory C. difficile infection to innovative, safe treatment, with a high success rate and little available in Brazil. Proper selection of qualified donors is vital in the process of implementing a FMTC. The rigorous clinical evaluation of donors allowed the rational use of resources. A transplant center enables treatment on demand, on a larger scale, less personalized, with more security and traceability. This protocol provides subsidies for conducting FMT in emerging countries.

RESUMO CONTEXTO: O Transplante de microbiota fecal (TMF) é uma importante opção terapêutica para a infecção recorrente ou refratária pelo Clostridioides difficile, sendo método seguro e eficaz. Resultados iniciais sugerem que o TMF também desempenha papel relevante em outras afecções cuja patogênese envolve a alteração da microbiota intestinal. No entanto, seu uso sistematizado é pouco difundido, especialmente no Brasil. Na última década, surgiram múltiplos relatos e séries de casos utilizando diferentes protocolos para o TMF, sem padronização de métodos e com taxas de resposta variáveis. No Brasil, poucos casos isolados de TMF foram relatados sem a implantação de um Centro de Transplante de Microbiota Fecal (CTMF). OBJETIVO: O principal objetivo deste estudo foi descrever o processo de implantação de um CTMF com banco de fezes, em hospital universitário brasileiro, para tratamento de infecção recorrente e refratária pelo C. difficile. MÉTODOS: O CTMF foi estruturado dentro dos critérios exigidos e aprovados por organismos internacionais como o Food and Drug Administration, Grupo Europeu de Transplante de Microbiota Fecal e em consonância com os aspectos epidemiológicos e regulatórios nacionais. RESULTADOS: Foi estabelecida toda uma plataforma envolvida na estruturação de um centro de transplante com fezes congeladas. Determinou-se os critérios para seleção de doadores, processamento e armazenamento de amostras, manejo dos receptores antes e após o procedimento, uniformização de vias de administração do substrato fecal e seguimento a curto e longo prazo dos pacientes transplantados. A seleção dos doadores foi conduzida em três etapas: pré-triagem, avaliação clínica e exames laboratoriais. Boa parte dos candidatos foram excluídos na primeira (75,4%) e segunda etapa (72,7%). Os principais critérios clínicos de exclusão foram: diarreia aguda recente, excesso de peso (IMC ≥25 kg/m2) e distúrbios gastrointestinais crônicos. Quatro dos 134 candidatos foram selecionados após a triagem completa, com taxa de detecção de doadores de 3%. CONCLUSÃO: A implantação de um CTMF, inédito no nosso meio, possibilita o acesso de pacientes com infecção recorrente e refratária pelo C. difficile a tratamento inovador, seguro, com elevada taxa de sucesso e pouco disponível no Brasil. A seleção apropriada de doadores qualificados é vital no processo de implantação de um CTMF. A avaliação clínica rigorosa dos doadores permitiu o uso racional de recursos para realização de exames laboratoriais. Um CTMF possibilita tratamento sob demanda, em maior escala, menos personalizados, com mais segurança e rastreabilidade. Este protocolo fornece subsídios para a realização de TMF em países emergentes.

A história do estetoscópio e da ausculta cardíaca / The history of the stethoscope and cardiac auscultation

Este trabalho apresenta os principais fatos e acontecimentos relacionados ao desenvolvimento do estetoscópio e à história da ausculta cardíaca. Destaca o papel e contribuição de diversas personalidades do campo científico, apresenta o estetoscópio em seus variados modelos históricos e sumariza as descobertas realizadas pelo método antes e depois da invenção desse instrumento. Aborda, ainda, a ausculta e o estetoscópio no contexto do exame físico e da construção da relação médico-paciente.

This paper reports the major facts and events related to the stethoscope development and the history of cardiac auscultation. It describes the role and contribution of several scientists, presents the several historical models of stethoscopes, and summarizes the discoveries relying on the auscultation method both before and after the invention of the stethoscope. It also approaches auscultation and stethoscope within the context of physical examination and physician-patient relationship

Cardiotoxicidade induzida por quimioterápicos: [revisão] / Chemotherapy induced cardiotoxicity: [review]

A sobrevida dos pacientes com câncer aumentou consideravelmente nos últimos 20 anos e, com ela,o número de eventos adversos associados aos quimioterápicos. A cardiotoxicidade crônica induzida pelos agentes antineoplásicos pode comprometer a sobrevida e a qualidade de vida dos pacientes, independentemente de seu prognóstico oncológico. Inúmeros fármacos foram associados a eventos adversos cardiovasculares, e até o momento não há protocolos bem estabelecidos para se detectar precocemente a toxicidade cardíaca. Alguns métodos auxiliam o diagnóstico, como o ecocardiograma, a dosagem de marcadores bioquímicos como a troponina I e o peptídeo natriurético, e a biópsia endomiocárdica. A cardiotoxicidade induzida por quimioterápicos tem se mostrado irreversível e ,uma vez estabelecida a disfunção miocárdica, seu tratamento independe do agente associado à indução da lesão. Estudos recentes sugerem o papel de agentes específicos como o dexrazoxane, a eritropoietina, a trombopoietina e os inibidores da enzima conversora de angiotensina na prevenção do desenvolvimento de cardiotoxicidade relacionada à quimioterapia.

Life expectancy of cancer patients has considerably increased in the last 20 years, but adverseevents associated to chemotherapy have also been more frequent. Chronic cardiactoxicity of antineoplastic agents can compromise survival and quality of life, independentof the oncological prognosis. A wide range of chemotherapy drugs have been associatedto cardiovascular adverse events, and until nowadays there are no well establishedprotocols for early detection of cardiac toxicity. Some methods help in identifying initialcardiomyopathy, such as the echocardiogram, the biochemical markers troponin I andnatriuretic peptide, and endomiocardial biopsy. Chemotherapy induced cardiotoxicityseems to be irreversible, and once myocardial dysfunction is established, the treatmentis not dependent of the causative drug. Recent studies suggest a role for specific agentssuch as dexrazoxan, eritropoietin, thrombopoietin and angiotensin converting enzymeinhibitors in preventing chemotherapy induced cardiotoxicity.

Choque cardiogênico na miocardiopatia induzida por agentes antineoplásicos: relato de caso / Cardiogenic shock in cardiomyopathy induced by antineoplastic agents: a case report

No Brasil, a principal etiologia da insuficiência cardíaca (IC) é a cardiopatia isquêmica crônica associada à hipertensão arterial. A IC pode se manifestar como doença crônica estável ou descompensada. A IC descompensada pode se apresentar como edema agudo de pulmão ou choque cardiogênico no atendimento de urgência. Este trabalho descreve a evolução de paciente admitida em unidade de pronto-socorro com choque cardiogênico secundário à miocardiopatia induzida por agentes antineoplásicos, manifesta quatro anos após a quimioterapia para câncer de mama.

The main cause of heart failure (HF) in Brazil is ischemic cardiomyopathy associated to arterial hypertension. HF can present as a chronic stable or as a decompensated disease. Decompensated HF can manifest as acute pulmonary edema and cardiogenic shock in the emergency unit. We describe here a patient admitted to an emergency room with cardiogenic shock secondary to cardiomyopathy induced by antineoplastic agents, 4 years after chemotherapy for breast cancer.