Hemophagocytic syndrome associated with hepatitis A: case report and literature review

Virus-Associated Hemophagocytic Syndrome (VAHS) is a severe hematological disorder related to some viral infections. It is an illness characterized by persistent fever, pancytopenia, splenomegaly, hyperferritinemia and, the most important, hemophagocytosis observed in the bone marrow, liver and/or lymph nodes. VAHS associated with hepatitis A virus infection is rarely described, despite the high incidence of this viral infection in the population in general. There is no consensus in the literature regarding the optimal treatment of VAHS. In this article the clinical features, presumed pathogenesis, diagnostic criteria and treatment of VAHS are discussed, including description of cases of VAHS related to hepatitis A virus infection found in the medical literature.A síndrome hemofagocitária associada a vírus é uma doença hematológica grave relacionada com algumas síndromes virais. É doença caracterizada por febre persistente, pancitopenia, esplenomegalia, hiperferritinemia e hemofagocitose na medula óssea, fígado e/ou linfonodos. A síndrome hemofagocitária associada ao vírus da hepatite A é raramente descrita, apesar da alta incidência desta infecção viral na população como um todo. Não existem consensos na literatura a respeito do tratamento desta morbidade. Neste artigo, os aspectos clínicos, patogênese, critérios diagnósticos e tratamento da síndrome hemofagocitária associada a vírus, incluindo a descrição de casos publicados da síndrome associada ao vírus da hepatite A

The health facility as a risk factor for multidrug-resistant gram-negative bacteria in critically ill patients with COVID-19

Background: The relationship between Multidrug Resistant-Gram Negative Bacteria (MDR-GNB) infection and colonization in critically ill COVID-19 patients has been observed, however, it is still poorly understood. This study evaluated the risk factors for acquiring MDR-GNB in patients with severe COVID-19 in Intensive Care Units (ICU). Methods: This is a nested case-control study in a cohort of 400 adult patients (≥ 18 years old) with COVID-19, hospitalized in the ICU of 4 hospitals in the city of Curitiba, Brazil. Cases were critical COVID-19 patients with one or more MDR GNB from any surveillance and/or clinical cultures were taken during their ICU stay. Controls were patients from the same units with negative cultures for MDR-GNB. Bivariate and multivariate analyses were done. Results: Sixty-seven cases and 143 controls were included. Independent risk factors for MDR bacteria were: male gender (OR = 2.6; 95% CI 1.28‒5.33; p = 0.008); the hospital of admission (OR = 3.24; 95% CI 1.39‒7.57; p = 0.006); mechanical ventilation (OR = 25.7; 95% CI 7.26‒91; p < 0.0001); and desaturation on admission (OR = 2.6; 95% CI 1.27‒5.74; p = 0.009). Conclusions: Male gender, desaturation, mechanical ventilation, and the hospital of admission were the independent factors associated with MDR-GNB in patients in the ICU with COVID-19. The only modifiable factor was the hospital of admission, where a newly opened hospital posed a higher risk. Therefore, coordinated actions toward a better quality of care for critically ill COVID-19 patients are essential

The German National Registry of Primary Immunodeficiencies (2012-2017)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment

Risk factors for mortality in patients with ventilator-associated pneumonia caused by carbapenem-resistant Enterobacteriaceae

Background: The ideal therapeutic option for ventilator associated pneumonia caused by carbapenem-resistant Enterobacteriaceae is not defined. The aim of this study was to assess mortality-associated risk factors in patients with VAP by CRE and determine the outcome of several treatment options. Methods: This was a retrospective study performed in two tertiary hospitals involving patients with VAP caused by CRE between January 2010 and August 2014. The outcomes were mortality within 30 days of VAP diagnosis and overall mortality during hospital admission. Risk factors for mortality were assessed by comparing variables of survivors and non-survivors. Results: One hundred and twelve patients with CRE-VAP were included, 73 (65%) male, median age 56 years. The 30-day mortality was 57.1% and the overall hospital mortality was 67%. In the binary logistic regression analysis, only age >50 years was independently associated to increased mortality. Polymyxin was the most used drug (47.5%), followed by tigecycline (29.2%) and aminoglycosides (2.4%). Combined therapy with two active drugs was used by 17 patients (20.8%). No therapeutic option was independently associated to survival. However, combined therapy with two active drugs was superior to the therapy with a single active drug when inappropriate therapy was the comparator (p = 0.044). The addition of carbapenem was not associated with increased survival. Conclusion: The best therapeutic option for VAP by CRE is still not completely defined, but the therapy with at least two active drugs was superior in this study. Keywords: Carbapenemase-producing Klebsiella pneumoniae, Ventilator-associated pneumonia, Risk factors, Mortality, Treatmen

STEWARDSHIP EM UM HOSPITAL DE TRAUMA NO SUL DO BRASIL

Introdução: Stewardship é um termo que abrange as ações dentro de um local de assistência à saúde que objetivam o uso racional de antimicrobianos, visando tanto um melhor desfecho para os pacientes, quanto a prevenção do desenvolvimento de resistência bacteriana. O objetivo do presente estudo é realizar a análise do Stewardship em um hospital terciário essencialmente cirúrgico. Materiais e métodos: Obteve-se informações referentes à antibioticoterapia de pacientes internados no Hospital do Trabalhador nos meses de abril e maio de 2023, bem como às intervenções propostas pelo centro de controle de infecção hospitalar. A realização do stewardship conta com checagem diária das culturas por farmacêuticos e avaliação do uso de antimicrobianos pela equipe de infectologia, através de participação nas visitas multidisciplinares das Unidades de Terapia Intensiva (UTIs) e respostas a pedidos de consulta diários com evoluções em prontuário. Resultados: Observou-se um total de 381 intervenções realizadas e acompanhamento de 1092 casos. A UTI foi o setor com maior número de casos avaliados (n = 888), entretanto onde houve menor demanda de intervenção (n = 194). Os antibióticos mais comumente avaliados foram cefepime (13%), meropenem (13,8%) e piperacilina+tazobactam (11,3%). O “switch oral” e “Iniciar tratamento antimicrobiano” foram as intervenções feitas com maior frequência (8,98 e 8,80%, respectivamente). A taxa de aceitabilidade geral das intervenções propostas foi de 82,82%, sendo a UTI o local com maior grau de aceitação (95 a 100%), e o setor de pronto-atendimento, o de menor (74,07%). Conclusão: Estudos recentes evidenciam que até 1/3 da prescrição de antibióticos em hospitais é feita de maneira desnecessária ou inadequada. Na UTI observou-se uma menor necessidade de ajustes na terapia antimicrobiana e uma alta aceitabilidade das sugestões, evidenciando um ambiente de cuidados intensivos preparado e receptivo a propostas de melhoria. A baixa aceitação no pronto-atendimento, por sua vez, pode representar um viés de amostra, uma vez que foram sugeridas somente 27 intervenções neste setor no período observado. O stewardship está relacionado à boa prática médica. Em um hospital referência em trauma, com alto fluxo de pacientes, o stewardship contribui para para minimizar a resistência microbiana e também para o maior giro de leitos, à medida que as intervenções realizadas (como o “switch oral”, por exemplo) otimizam o processo de alta hospitalar

PERFIL MICROBIOLÓGICO E DE RESISTÊNCIA BACTERIANA EM UM HOSPITAL ESSENCIALMENTE CIRÚRGICO

Introdução: A análise do perfil microbiológico de um hospital, bem como do perfil de resistência dos microrganismos, é uma ferramenta de extrema utilidade na prevenção e combate de infecções relacionadas à assistência à saúde (IRAS). Nesse trabalho expomos a análise microbiológica de um hospital referência de atendimentos de trauma e comorbidades cirúrgicas. Materiais e métodos: Coleta de dados referentes a todas as culturas das IRAS com resultado positivo e perfis de resistência dos germes isolados realizadas no Hospital do Trabalhador no período de janeiro a maio de 2023. Resultados: Informações de 476 culturas positivas foram obtidas. Os microrganismos isolados com maior frequência foram Staphylococcus aureus (11,13%), Enterococcus faecalis (8,19%), e Escherichia coli (6,93%). Beta-lactamases de espectro estendido (ESBL) foi o mecanismo de resistência observado com maior frequência (56,57%), seguido pela resistência à meticilina (MRSA) (23,21%) em S. aureus. 44,95% das culturas positivas tinha como quadro clínico primário a infecção de sítio cirúrgico (ISC). A prevalência de culturas positivas de infecção de trato urinário não relacionada à sonda e a de pneumonia não associada à ventilação mecânica foram de 15,75% e 10,50%, respectivamente. Conclusão: Segundo o Sistema Online de Notificação de Infecção Hospitalar (SONIH) referente ao estado do Paraná no ano de 2022, o microrganismo mais frequentemente isolado em culturas de IRAS foi Klebsiella pneumoniae, seguida de Pseudomonas aeruginosa e o complexo Acinetobacter baumannii. É possível notar a diferença marcante com os dados do nosso hospital, essencialmente cirúrgico, que tem a ISC como suspeita diagnóstica mais frequente levando à coleta de culturas, justificando o fato de que os germes isolados mais vezes são os cocos gram positivos. No estado do Paraná em 2022 o SONIH evidenciou que 26,33% dos S. aureus isolados em ISC eram MRSA. O HT apresentou dados semelhantes, com 24,52% dos S. aureus apresentando resistência à meticilina. A análise sistemática do perfil microbiano é fundamental para guiar tratamentos antimicrobianos empíricos, bem como para realização de ações de prevenção da disseminação de bactérias multirresistentes no ambiente hospitalar

Cyclin-dependent kinases 4 and 6 control tumor progression and direct glucose oxidation in the pentose cycle

Cyclin-dependent kinases CDK4 and CDK6 are essential for the control of the cell cycle through the G1 phase. Aberrant expression of CDK4 and CDK6 is a hall- mark of cancer, which would suggest that CDK4 and CDK6 are attractive targets for cancer therapy. Herein, we report that calcein AM is a potent specific inhibitor of CDK4 and CDK6 in HCT116 human colon adenocarcinoma cells, inhibiting retinoblastoma protein (pRb) phosphorylation and inducing cell cycle arrest in the G1 phase. The metabolic effects of calcein AM (the calcein acetoxymethyl-ester) on HCT116 cells were also evaluated and the flux between the oxidative and non-oxidative branches of the pentose phos-phate pathway was significantly altered. To elucidate whe-ther these metabolic changes were due to the inhibition of CDK4 and CDK6, we also characterized the metabolic profile of a CDK4, CDK6 and CDK2 triple knockout of mouse embryonic fibroblasts. The results show that the metabolic profile associated with the depletion of CDK4, CDK6 and CDK2 coincides with the metabolic changes induced by calcein AM on HCT116 cells, thus confirming that the inhibition of CDK4 and CDK6 disrupts the balance between the oxidative and non-oxidative branches of the pentose phosphate pathway. Taken together, these results indicate that low doses of calcein can halt cell division and kill tumor cells. Thus, selective inhibition of CDK4 and CDK6 may be of greater pharmacological interest, since inhibitors of these kinases affect both cell cycle progression and the robust metabolic profile of tumors