Maintenance of chronicity signatures in fibroblasts isolated from recessive dystrophic epidermolysis bullosa chronic wound dressings under culture conditions

BACKGROUND: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a rare inherited skin disease caused by variants in the COL7A1 gene, coding for type VII collagen (C7), an important component of anchoring fibrils in the basement membrane of the epidermis. RDEB patients suffer from skin fragility starting with blister formation and evolving into chronic wounds, inflammation and skin fibrosis, with a high risk of developing aggressive skin carcinomas. Restricted therapeutic options are limited by the lack of in vitro models of defective wound healing in RDEB patients. RESULTS: In order to explore a more efficient, non-invasive in vitro model for RDEB studies, we obtained patient fibroblasts derived from discarded dressings) and examined their phenotypic features compared with fibroblasts derived from non-injured skin of RDEB and healthy-donor skin biopsies. Our results demonstrate that fibroblasts derived from RDEB chronic wounds (RDEB-CW) displayed characteristics of senescent cells, increased myofibroblast differentiation, and augmented levels of TGF-ß1 signaling components compared to fibroblasts derived from RDEB acute wounds and unaffected RDEB skin as well as skin from healthy-donors. Furthermore, RDEB-CW fibroblasts exhibited an increased pattern of inflammatory cytokine secretion (IL-1ß and IL-6) when compared with RDEB and control fibroblasts. Interestingly, these aberrant patterns were found specifically in RDEB-CW fibroblasts independent of the culturing method, since fibroblasts obtained from dressing of acute wounds displayed a phenotype more similar to fibroblasts obtained from RDEB normal skin biopsies. CONCLUSIONS: Our results show that in vitro cultured RDEB-CW fibroblasts maintain distinctive cellular and molecular characteristics resembling the inflammatory and fibrotic microenvironment observed in RDEB patients' chronic wounds. This work describes a novel, non-invasive and painless strategy to obtain human fibroblasts chronically subjected to an inflammatory and fibrotic environment, supporting their use as an accessible model for in vitro studies of RDEB wound healing pathogenesis. As such, this approach is well suited to testing new therapeutic strategies under controlled laboratory conditions.

Efectos negativos en la investigación y el quehacer médico en Chile de la Ley 20.584 y la Ley de Neuroderechos en discusión: la urgente necesidad de aprender de nuestros errores / Negative effects of the patients' rights law and neuro-rights bill in Chile

Recently, the Chilean Senate approved the main ideas of a constitutional reform and a Neuro-rights bill. This bill aims to protect people from the potential abusive use of "neuro-technologies". Unfortunately, a literal interpretation of this law can produce severe negative effects both in the development of neuroscience research and medical practice in Chile, interfering with current treatments in countless patients suffering from neuropsychiatric diseases. This fear stems from the observation of the negative effects that recent Chilean legislations have produced, which share with the Neuro-Rights Law the attempt to protect vulnerable populations from potential abuse from certain medical interventions. In fact, Law 20,584 promulgated in 2012, instead of protecting the most vulnerable patients "incapacitated to consent", produced enormous, and even possibly irreversible, damage to research in Chile in pathologies that require urgent attention, such as many neuropsychiatric diseases. This article details the effects that Law 20.584 had on research in Chile, how it relates to the Neuro-Rights Law, and the potential negative effects that the latter could have on research and medical practice, if it is not formulated correcting its errors.

Recomendaciones para la ejecución de anestesia regional no obstétrica en perioperatorio de pacientes COVID-19 / Recommendations for the execution of non-obstetric regional anesthesia in treatment of COVID-19 patients

En diciembre de 2019, surgió una serie de casos de neumonía causada por un nuevo coronavirus, denominado 2019-nCoV o SARS-CoV2. La propagación del virus ha sido extremadamente rápida y la organización mundial de la salud declaró a la enfermedad COVID-19, causada por 2019-nCoV, como una pandemia. En este contexto la Sociedad de Anestesiología de Chile (SACH) ha elaborado recomendaciones generales para el manejo perioperatorio de los pacientes sospechosos y/o portadores de la enfermedad. Sin embargo, dado que durante el levantamiento de evidencia para la confección de dicha guía se objetivó la ausencia de sugerencias específicas para la ejecución de técnicas de anestesia regional fuera del ambiente obstétrico, se solicitó desde el Comité Científico de SACH al Comité de Anestesia Regional de SACH (CARSACH), representante LASRA (LatinAmerican Society of Regional Anesthesia) en Chile, a través de un grupo de expertos, confeccionar recomendaciones locales en esta materia.

Perioperative lumbar plexus block and cardiac ischemia in patients with hip fracture: randomized clinical trial / Bloqueio perioperatório do plexo lombar e isquemia cardíaca em pacientes com fratura de quadril: ensaio clínico randomizado

Abstract Background Perioperative myocardial ischemia is common among patients undergoing hip fracture surgery. Our aim is to evaluate the efficacy of perioperative continuous lumbar plexus block in reducing the risk of cardiac ischemic events of elderly patients undergoing surgery for hip fractures, expressed as a reduction of ischemic events per subject. Methods Patients older than 60 years, ASA II-III, with risk factors for or known coronary artery disease were enrolled in this randomized controlled study. Patients were randomized to conventional analgesia using opioid intravenous patient-controlled analgesia or continuous lumbar plexus block analgesia, both started preoperatively and maintained until postoperative day three. Continuous electrocardiogram monitoring with ST segment analysis was recorded. Serial cardiac enzymes and pain scores were registered during the entire period. We measured the incidence of ischemic events per subject registered by a continuous ST-segment Holter monitoring. Results Thirty-one patients (intravenous patient-controlled analgesia 14, lumbar plexus 17) were enrolled. There were no major cardiac events during the observation period. The number of ischemic events recorded by subject during the observation period was 6 in the lumbar plexus group and 3 in the intravenous patient-controlled analgesia group. This difference was not statistically significant (p = 0.618). There were no statistically significant differences in the number of cases with increased perioperative troponin values (3 cases in the lumbar plexus group and 1 case in the intravenous patient-controlled analgesia group) or in terms of pain scores. Conclusions Using continuous perineural analgesia, compared with conventional systemic analgesia, does not modify the incidence of perioperative cardiac ischemic events of elderly patients with hip fracture.

Resumo Justificativa A isquemia miocárdica perioperatória é comum em pacientes submetidos à cirurgia de fratura de quadril. Nosso objetivo foi avaliar a eficácia do bloqueio perioperatório contínuo do plexo lombar na redução do risco de eventos cardíacos isquêmicos em pacientes idosos submetidos à cirurgia para fraturas de quadril, expresso como uma redução de eventos isquêmicos por indivíduo. Métodos Pacientes com mais de 60 anos de idade, ASA II-III com fatores de risco para ou com doença coronariana conhecida foram incluídos neste estudo controlado e randomizado. Os pacientes foram aleatorizados para analgesia convencional usando analgésicos opioides para administração de analgesia intravenosa controlada pelo paciente (Intravenous Patient-Controlled Analgesia - IVPCA) ou analgesia contínua com o bloqueio do Plexo Lombar (PL), ambas iniciadas no pré-operatório e mantidas até o terceiro dia de pós-operatório. Monitoração contínua de ECG com análise do segmento ST foi registrada. Enzimas cardíacas seriadas e escores de dor foram registrados durante todo o período. Medimos a incidência de eventos isquêmicos por indivíduo registrados com monitoração contínua do segmento ST via Holter. Resultados Trinta e um pacientes (IVPCA 14, PL 17) foram incluídos. Não houve eventos cardíacos sérios durante o período de observação. O número de eventos isquêmicos registrados por sujeito durante o período de observação foi de seis no grupo PL e três no grupo IVPCA. Essa diferença não foi estatisticamente significativa (p = 0,618). Não houve diferenças estatisticamente significativas no número de casos com aumento dos valores de troponina no perioperatório (três casos no grupo LP e um caso no grupo IVPCA) ou em termos de escores de dor. Conclusões O uso da analgesia perineural contínua comparado ao da analgesia sistêmica convencional não modifica a incidência de eventos isquêmicos cardíacos no período perioperatório de pacientes idosos com fratura de quadril.

Acquiring skills in malignant hyperthermia crisis management: comparison of high-fidelity simulation versus computer-based case study / Adquirir habilidades no manejo de crises de hipertermia maligna: comparação de simulação de alta-fidelidade versus estudo de caso em computador

Abstract Introduction: The primary purpose of this study was to compare the effect of high fidelity simulation versus a computer-based case solving self-study, in skills acquisition about malignant hyperthermia on first year anesthesiology residents. Methods: After institutional ethical committee approval, 31 first year anesthesiology residents were enrolled in this prospective randomized single-blinded study. Participants were randomized to either a High Fidelity Simulation Scenario or a computer-based Case Study about malignant hyperthermia. After the intervention, all subjects' performance in was assessed through a high fidelity simulation scenario using a previously validated assessment rubric. Additionally, knowledge tests and a satisfaction survey were applied. Finally, a semi-structured interview was done to assess self-perception of reasoning process and decision-making. Results: 28 first year residents finished successfully the study. Resident's management skill scores were globally higher in High Fidelity Simulation versus Case Study, however they were significant in 4 of the 8 performance rubric elements: recognize signs and symptoms (p = 0.025), prioritization of initial actions of management (p = 0.003), recognize complications (p = 0.025) and communication (p = 0.025). Average scores from pre- and post-test knowledge questionnaires improved from 74% to 85% in the High Fidelity Simulation group, and decreased from 78% to 75% in the Case Study group (p = 0.032). Regarding the qualitative analysis, there was no difference in factors influencing the student's process of reasoning and decision-making with both teaching strategies. Conclusion: Simulation-based training with a malignant hyperthermia high-fidelity scenario was superior to computer-based case study, improving knowledge and skills in malignant hyperthermia crisis management, with a very good satisfaction level in anesthesia residents.

Resumo Introdução: O objetivo primário deste estudo foi comparar o efeito da simulação de alta-fidelidade versus autoestudo baseado em resolução de casos no computador, a aquisição de habilidades sobre hipertermia maligna em residentes de anestesiologia do primeiro ano. Métodos: Após a aprovação do Comitê de Ética institucional, 31 residentes de anestesiologia do primeiro ano foram inscritos neste estudo prospectivo, randômico e encoberto. Os participantes foram randomizados para um ambiente de simulação de alta-fidelidade (SAF) ou um estudo de caso (EC) em computador sobre hipertermia maligna. Após a intervenção, o desempenho de todos os indivíduos foi avaliado através de um ambiente de simulação de alta-fidelidade utilizando uma rubrica de avaliação previamente validada. Além disso, uma pesquisa de satisfação e testes de conhecimento foram aplicados. Por fim, uma entrevista semiestruturada foi realizada para avaliar a autopercepção do processo de raciocínio e da tomada de decisão. Resultados: Vinte e oito residentes do primeiro ano concluíram o estudo com sucesso. Os escores dos residentes na aquisição de habilidades no manejo da hipertermia maligna foram globalmente maiores no Grupo SAF que no Grupo EC, mas a significância foi em quatro dos oito elementos da rubrica de desempenho: reconhecer os sinais e sintomas (p = 0,025), priorizaras ações iniciais do manejo (p = 0,003), reconhecer complicações (p = 0,025) e comunicação (p = 0,025). As médias dos escores nos questionários de conhecimento pré- e pós-teste melhoraram de 74% para 85% no Grupo SAF e diminuíram de 78% para 75% no Grupo EC (p = 0,032). Em relação à análise qualitativa, não houve diferença nos fatores que influenciaram o processo de raciocínio e de tomada de decisão dos alunos com ambas as estratégias de ensino. Conclusão: O treinamento baseado em simulação com um ambiente de alta-fidelidade de hipertermia maligna foi superior ao estudo de caso em computador, melhorou o conhecimento e as habilidades no manejo de crises de hipertermia maligna, com um nível de satisfação muito bom entre os residentes de anestesia.

Simulación de eventos críticos en anestesia: lecciones y aprendizaje desde la aviación para mejorar la seguridad del paciente / Simulation of critical events in anesthesia: lessons and learning from aviation to improve patient safety

: Durante décadas, las industrias de alto riesgo tales como la aviación comercial, las plantas nucleares y la ingeniería militar han sido entrenadas en el manejo de eventos críticos. En salud, la aplicación de los conceptos del entrenamiento del equipo de aviación y Crew Resource Management ("manejo de los recursos en crisis"), particularmente en anestesia, se han utilizado para mejorar la seguridad del paciente. Los eventos críticos, definidos como el punto en el curso de una enfermedad en la que se produce un cambio decisivo que conduce a la recuperación o a la muerte, tienen muchas características ideales para el entrenamiento por simulación.En esta revisión narrativa, nuestro objetivo es definir los conceptos y la relación entre eventos críticos y simulación en anestesia, determinando su uso en el manejo de dichos eventos y la evidencia existente para apoyarlo.(AU)

For decades, high-risk industries such as commercial aviation, nuclear plants and military engineering have been trained successfully in managing critical events. In healthcare, translating concepts of aviation team training and Crew Resource Management particularly to anesthesia has been used to improve patient safety. Critical events, defined as the point in the course of a disease at which a decisive change occurs, leading either to recovery or death, have many features that are fulfilled by simulation training. In this narrative review we aim to define the concepts and the relation between critical events and simulation in anesthesia, determining the uses of simulation in managing critical events and the evidence to support it.(AU)

La simulación puede mejorar la seguridad de los pacientes sometidos a procedimientos endoscópicos gastrointestinales bajo sedación / Simulation can improve patients’ security in gastrointestinal endoscopic procedures under sedation

background: Appropriate sedation is crucial for a successful gastrointestinal endoscopy procedure (GEP); however, this is associated with adverse events, therefore adequate capacitation in this subject is mandatory. Simulation is an excellent teaching tool but its use in the setting of sedation teaching for GEP has not bee explored. The aim of this study was to assess the impact of a simulation course on sedation for GEP procedures done by endoscopist. Methods: A checklist to assess the endoscopists’ sedation performance for GEP was developed. This checklist was used to assess the sedations’ quality before and after a high fidelity sedation simulation course for GEP. Differences before/after the intervention was calculated using the McNemar’s test. A p ≤ 0,05 was considered significant. Results: All participants were assessed 15 times pre and post intervention. After the simulation, there was a significant improvement in patients’ airway assessment, in the level of awareness about patients’ condition during the procedure and in the monitoring after the procedure. All participants considered simulation should be compulsory before obtaining a license to sedate patients. Conclusions: The implementation of a sedation course based on simulation cases directed to endoscopists improved patient safety and sedations’ quality during the procedure. Simulation should be considered as a valid teaching tool, which is an enormous challenge to the anaesthesiologists.

Introducción: Una adecuada sedación contribuye al éxito de un procedimiento endoscópico gastrointestinal (PEG); sin embargo, esto puede estar asociado a eventos adversos, siendo importante la capacitación al respecto. La simulación es una excelente herramienta docente, pero su uso en la enseñanza de sedación para PEG no ha sido explorada. El objetivo de este estudio fue evaluar el impacto de un curso de sedación para PEG dirigido a endoscopistas basado en simulación. Materiales y Métodos: Se diseño una lista de cotejo para evaluar la calidad de la sedación impartida por endoscopistas durante PEG. Con dicho instrumento se determinó la calidad de la sedación antes y después de un curso de simulación de alta fidelidad sobre sedación para PEG. La magnitud de las diferencias secundario a la intervención se calcularon utilizando el test de McNemar. Una p ≤ 0,05 se consideró significativa. Resultados: Todos los participantes fueron evaluados 15 veces antes y después de la intervención. Después de la intervención, mejoró significativamente la evaluación de vía aérea, el nivel de alerta por las condiciones del paciente durante el procedimiento y el seguimiento posterior. Todos los participantes consideraron que la simulación debería ser obligatoria antes de obtener privilegios clínicos. Conclusiones: La implementación de un curso de sedación basados en simulación dirigidos a endoscopistas mejora la calidad de esta y la seguridad del paciente durante el procedimiento. La simulación debe ser considerada como una estrategia de enseñanza válida en este contexto lo que plantea un gran desafío a todos los anestesiólogos.