The viability of using epigenetic drugs as a treatment of patients in sepsis - a translational perspective

Sepsis is a serious and potentially lethal clinical condition characterized by dysregulated immune and systemic inflammatory responses (SIRS) to an infection. Although sepsis has a high mortality rate (reaching 25% in Europe and North America), the clinical interventions available are still limited. In the bottom of this exacerbation of the immune response, that evolves to immunosuppression and immune paralysis, lies epigenetic mechanisms. In sepsis, the balance between activated and repressed immune related genes is at lost, and to recover that epigenetic based drugs promises to be the future of sepsis treatment. Histone deacetylase inhibitors (HDAC’s inhibitors) are drugs based in the epigenetic mechanism of acetylation and deacetylation of histones, and they have already been tested - phases three and four of clinical trials - as treatment for other diseases, such as multiple myeloma, and cutaneous t-cell lymphoma. Furthermore, experimental studies in sepsis models shows that HDAC’s inhibitors are a promising suppressor of the exacerbated inflammatory response. Therefore, as the recent works shows, epigenetic drugs should be considered a viable sepsis therapy in the future. The focus of this review is to present the most recent scientific advances in the basic and clinical areas of epigenetic as a sepsis treatment, opening opportunities for the use of epigenetic in treating this condition.Sepse é uma condição clínica grave e potencialmente letal caracterizada por desreguladas respostas imunes e inflamatórias sistêmicas (SIRS) a uma infecção. Embora a sepse tenha uma alta taxa de mortalidade (atingindo 25% na Europa e América do Norte), as intervenções clínicas disponíveis ainda são limitadas. Por trás dessa exacerbação da resposta imunológica, que evolui para a imunossupressão e paralisia imune, residem mecanismos epigenéticos. Na sepse, o equilíbrio entre genes imunes ativados e reprimidos relacionados é perdido, e reaver drogas baseadas na epigenética promete ser o futuro do tratamento da sepse. Inibidores da histona desacetilase (inibidores de HDAC) são drogas baseadas no mecanismo epigenético de acetilação e desacetilação de histonas, e eles já têm sido testados - fases três e quatro de ensaios clínicos - como tratamento para outras doenças, tais como o mieloma múltiplo, e linfoma cutâneo de células T. Além disso, os estudos experimentais em modelos de sepse mostram que os inibidores de HDAC são promissores supressores da resposta inflamatória exacerbada. Portanto, como os trabalhos recentes mostraram, drogas epigenéticas poderiam ser consideradas uma viável terapia para a sepse no futuro. O foco desta revisão é apresentar os mais recentes avanços científicos nas áreas básicas e clínicas de epigenética como um tratamento da sepse, abrindo oportunidades para o uso da epigenética no tratamento desta condição

Can artificial intelligence improve the management of pneumonia

The use of artificial intelligence (AI) to support clinical medical decisions is a rather promising concept. There are two important factors that have driven these advances: the availability of data from electronic health records (EHR) and progress made in computational performance. These two concepts are interrelated with respect to complex mathematical functions such as machine learning (ML) or neural networks (NN). Indeed, some published articles have already demonstrated the potential of these approaches in medicine. When considering the diagnosis and management of pneumonia, the use of AI and chest X-ray (CXR) images primarily have been indicative of early diagnosis, prompt antimicrobial therapy, and ultimately, better prognosis. Coupled with this is the growing research involving empirical therapy and mortality prediction, too. Maximizing the power of NN, the majority of studies have reported high accuracy rates in their predictions. As AI can handle large amounts of data and execute mathematical functions such as machine learning and neural networks, AI can be revolutionary in supporting the clinical decision-making processes. In this review, we describe and discuss the most relevant studies of AI in pneumonia

A systematic literature review and expert consensus on risk factors associated to infection progression in adult patients with respiratory tract or rectal colonisation by carbapenem-resistant Gram-negative bacteria

Multi-drug resistance; Risk factor; ColonizationResistencia a múltiples fármacos; Factor de riesgo; ColonizaciónResistència a múltiples fàrmacs; Factor de risc; ColonitzacióObjective. Risk factors (RFs) associated with infection progression in patients already colonised by carbapenem-resistant Gram-negative bacteria (CRGNB) have been addressed in few and disperse works. The aim of this study is to identify the relevant RFs associated to infection progression in patients with respiratory tract or rectal colonisation. Material and methods. A systematic literature review was developed to identify RFs associated with infection progression in patients with CRGNB respiratory tract or rectal colonisation. Identified RFs were then evaluated and discussed by the expert panel to identify those that are relevant according to the evidence and expert’s experience. Results. A total of 8 articles were included for the CRGNB respiratory tract colonisation and 21 for CRGNB rectal colonisation, identifying 19 RFs associated with pneumonia development and 44 RFs associated with infection progression, respectively. After discussion, the experts agreed on 13 RFs to be associated with pneumonia development after respiratory tract CRGNB colonisation and 33 RFs to be associated with infection progression after rectal CRGNB colonisation. Respiratory tract and rectal colonisation, previous stay in the ICU and longer stay in the ICU were classified as relevant RF independently of the pathogen and site of colonisation. Previous exposure to antibiotic therapy or previous carbapenem use were also common relevant RF for patients with CRGNB respiratory tract and rectal colonisation. Conclusion. The results of this study may contribute to the early identification of CRGNB colonized patients at higher risk of infection development, favouring time-to-effective therapy and improving health outcomes.This study was funded by Shionogi S.L.U

Impact on in-hospital mortality of ceftaroline versus standard of care in community-acquired pneumonia: a propensity-matched analysis

Abstract The purpose of this study is to evaluate the in-hospital mortality of community-acquired pneumonia (CAP) treated with ceftaroline in comparison with standard therapy. This was a retrospective observational study in two centers. Hospitalized patients with CAP were grouped according to the empiric regimen (ceftaroline versus standard therapy) and analyzed using a propensity score matching (PSM) method to reduce confounding factors. Out of the 6981 patients enrolled, 5640 met the inclusion criteria, and 89 of these received ceftaroline. After PSM, 78 patients were considered in the ceftaroline group (cases) and 78 in the standard group (controls). Ceftaroline was mainly prescribed in cases with severe pneumonia (67% vs. 56%, p=0.215) with high suspicion of Staphylococcus aureus infection (9% vs. 0%, p=0.026). Cases had a longer length of hospital stay (13 days vs. 10 days, p=0.007), while an increased risk of in-hospital mortality was observed in the control group compared to the case group (13% vs. 21%, HR 0.41; 95% CI 0.18 to 0.62, p=0.003). The empiric use of ceftaroline in hospitalized patients with severe CAP was associated with a decreased risk of in-hospital mortalit

La empresa MAXCOLCHON apuesta por la Innovación Orientada por las Personas

[ES] Conocer los aspectos más importantes que genera una experiencia de uso satisfactoria en los potenciales usuarios de un producto y el proceso de toma de decisión de la compra es clave para garantizar el éxito. Para conocer los aspectos y saber cómo los perciben los perfiles poblacionales concretos a los que va orientado el producto es imprescindible escuchar la voz de los usuarios. La Innovación Orientada por las Personas facilita una metodología validada para incluir a las personas en todas las fases del proceso de desarrollo, convirtiendo al usuario objetivo del producto en un recurso activo de generación de valor para las empresas. En esta línea, la empresa MAXCOLCHON ha desarrollado junto con el Instituto de Biomecánica (IBV) un proyecto que tiene como objetivo identificar los aspectos clave que tienen en cuenta los usuarios a la hora de valorar el colchón ONE y tomar la decisión de compra. A partir de dicha información es posible, desde trabajar en el desarrollo o mejora de un producto, hasta identificar la mejor forma de orientar una campaña de marketingSoriano Garcia, C.; Marzo Rosello, R.; Martínez Gómez, L.; Sanchís Almenara, M.; Mercader Ricos, A. (2020). La empresa MAXCOLCHON apuesta por la Innovación Orientada por las Personas. Revista de Biomecánica (Online). (67):1-5. http://hdl.handle.net/10251/176089S156

Emergence of Progressive Mutations in SARS-CoV-2 From a Hematologic Patient With Prolonged Viral Replication

We documented a hematologic patient with prolonged SARS-CoV-2 viral replication in whom emergence of viral mutations was documented after the consecutive use of antivirals and convalescent plasma. The virus detected in the last of 12 clinical samples (day 237) had accumulated 22 changes in amino acids and 29 in nucleotides. Some of these changes, such as the E484Q, were mutations of concern as defined by WHO. This finding represents an enormous epidemiological threat and poses a major clinical challenge. Combined antiviral strategies, as well as specific strategies related to the diagnostic approach of prolonged infections for this specific population, may be needed.This work has been financed by funds for research ad hoc COVID-19 from patronage provided by citizens and organizations to Hospital Clínic de Barcelona-Fundació Clínic per a la Recerca Biomèdica. This work received support from FONDO-COVID19 (ISCIII Grant number: COV20-00679), Instituto de Salud Carlos III (PI21/01640) and by European Region (ERDF, “A way to make Europe”). PP-A [JR20/00012 and PI21/00498], NG-P [FI19/00133], have also received research grants from the Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III. The funders had neither a specific role in study design or collection of data, nor in writing of the paper or decision to submit.S

Blunt traumatic diaphragmatic rupture

A incidência de lesão traumática do diafragma, relatada na literatura, varia de0,6 a 1,2% dentre os pacientes vítimas de traumas, elevando-se para 5% nospacientes com trauma fechado submetidos a laparotomia. A suspeita clínicaassociada à avaliação radiológica contribui para o diagnóstico precoce. Alesão diafragmática isoladamente é de bom prognóstico. Assim, em geral, aslesões associadas à rotura diafragmática são os preditores da pior evoluçãodo paciente. As lesões do diafragma direito e as lesões bilaterais apresentampior prognóstico. A tomografia computadorizada com multidetectores (MDCT)de tórax oferece a possibilidade de reconstrução multiplanar permitindomelhor acurácia no diagnóstico. A correção cirúrgica por meio de laparotomiae/ou toracotomia na fase aguda do trauma apresenta boa evolução e evitaas complicações crônicas da hérnia diafragmática. Os autores apresentam ocaso de um paciente jovem do sexo masculino, vítima de trauma abdominalfechado por acidente automobilístico que apresentou rotura do diafragma, lesãoesplênica e renal. O diagnóstico foi feito através da tomografia computadorizadade tórax e abdome e confirmada durante laparotomia exploradora.Traumatic injury of the diaphragm ranges from 0.6 to 1.2% and rise up to 5%among patients who were victims of blunt trauma and underwent laparotomy.Clinical suspicion associated with radiological assessment contributes to earlydiagnosis. Isolated diaphragmatic injury has a good prognosis. Generallyworse outcomes are associated with other trauma injuries. Bilateral andright diaphragmatic lesions have worse prognosis. Multi detector computed tomography (MDCT) scan of the chest and abdomen provides better diagnosticaccuracy using the possibility of image multiplanar reconstruction. Surgicalrepair via laparotomy and/ or thoracotomy in the acute phase of the injury hasa better outcome and avoids chronic complications of diaphragmatic hernia.The authors present the case of a young male patient, victim of blunt abdominaltrauma due to motor vehicle accident with rupture of the diaphragm, spleenand kidney injuries. The diagnosis was made by computed tomography of thethorax and abdomen and was confirmed during laparotomy

Risk factors for mortality in patients with acute leukemia and bloodstream infections in the era of multiresistance

Objectives: We assess the epidemiology and risk factors for mortality of bloodstream infection (BSI) in patients with acute leukemia (AL). Methods: Prospectively collected data of a cohort study from July 2004 to February 2016. Multivariate analyses were performed. Results: 589 episodes of BSI were documented in 357 AL patients, 55% caused by gram-positive bacteria (coagulase-negative staphylococci 35.7%, Enterococcus spp 10.8%) and 43.5% by gram-negative bacteria (E. coli 21%, PA 12%). We identified 110 (18.7%) multidrug-resistant (MDR) microorganisms, especially MDR-Pseudomonas aeruginosa (7%) and extended-spectrum beta-lactamase producing Enterobacteriaceae (7%). The 30-day mortality was 14.8%. Age (OR 3.1; 95% CI 1.7–5.7); chronic lung disease (4.8; 1.1–21.8); fatal prognosis according to McCabe index (13.9; 6.4–30.3); shock (3.8; 1.9–7.7); pulmonary infection (3.6; 1.3–9.9); and MDR-PA infections with inappropriate treatment (12.8; 4.1–40.5) were related to mortality. MDR-PA BSI was associated to prior antipseudomonal cephalosporin use (9.31; 4.38–19.79); current use of betalactams (2.01; 1.01–4.3); shock (2.63; 1.03–6.7) and pulmonary source of infection (9.6; 3.4–27.21). Conclusions: MDR organisms were commonly isolated in BSI in AL. Inappropriate empiric antibiotic treatment for MDR-PA is the primary factor related to mortality that can be changed. New treatment strategies to improve the coverage of MDR-PA BSI should be considered in those patients with risk factors for this infection