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Acute respiratory distress syndrome is associated with skeletal muscle compromise, which decreases survival and impairs functional capacity. A comparative analysis of peripheral and respiratory muscles' atrophy and dysfunction in acute lung injury (ALI) has not been performed. We aimed to evaluate diaphragmatic and peripheral muscle mass and contractility in an ALI animal model. ALI was induced in C57BL/6 mice by intratracheal lipopolysaccharides instillation. Muscle mass and in vitro contractility were evaluated at different time points in hindlimb soleus (slow-twitch) and extensor digitorum longus (EDL, fast-twitch), as well as in the main respiratory muscle diaphragm. Myogenic precursor satellite cell-specific transcription factor Pax7 expression was determined by Western blot. Lung injury was associated with atrophy of the three studied muscles, although it was more pronounced and persistent in the diaphragm. Specific contractility was reduced during lung injury in EDL muscle but restored by the time lung injury has resolved. Specific force was not affected in soleus and diaphragm. A persistent increase in Pax7 expression was detected in diaphragm and EDL muscles after induction of ALI, but not in soleus muscle. Different peripheral and respiratory skeletal muscles are distinctly affected during the course of ALI. Each of the studied muscles presented a unique pattern in terms of atrophy development, contractile dysfunction and Pax7 expression.

Certain parameters of complete blood count (CBC) such as red cell distribution width (RDW) and mean platelet volume, as well as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and RDW-to-platelet ratio (RPR) have been associated with inflammatory status and outcome in diverse medical conditions. The aim of this study was to describe the evolution pattern of these parameters in adult burned patients. Adult burned patients admitted to the National Burn Center in Uruguay between May 2017 and February 2018 (discovery cohort) and between March 2018 and August 2019 (validation cohort) were included. Patients’ characteristics and outcomes were recorded, as well as CBC parameters on days 1, 3, 5, and 7 after thermal injury. Eighty-eight patients were included in the discovery cohort. Total body surface area burned was 14 [7–23]% and mortality was 15%. Nonsurvivors presented higher RDW and mean platelet volume (P < .01). NLR decreased after admission in all patients (P < .01), but was higher in nonsurvivors (P < .01). Deceased patients also presented higher RPR on days 3, 5, and 7 (P < .001). On the contrary, PLR was reduced in nonsurvivors (P < .05). There was a significant correlation between NLR on admission and burn extension and severity. Kaplan–Meier analysis revealed that NLR, PLR, and RPR could identify patients with increased mortality. These findings were confirmed in the validation cohort (n = 95). Basic CBC parameters and derived indices could be useful as biomarkers to determine prognosis in adults with thermal injuries.

RESUMO Resumo: Determinar os fatores independentes de risco associados com mortalidade em pacientes queimados adultos. Métodos: Estudo observacional retrospectivo, conduzido no Centro Nacional de Queimados do Uruguai. Incluíram-se todos os pacientes com queimaduras da pele admitidos à unidade desde sua inauguração em 1° de julho de 1995 até o dia 31 de dezembro de 2018. Estudaram-se os dados demográficos, perfis de queimadura, tempo de permanência, duração da ventilação mecânica e mortalidade hospitalar. Utilizou-se regressão logística multivariada para identificação dos fatores de risco para mortalidade. A proporção padronizada de mortalidade foi calculada pela divisão do número de óbitos observados pelo número de óbitos previstos, segundo o Abbreviated Burn Severity Index. Resultados: Durante o período do estudo, incluímos 3.112 pacientes. A mediana da área total de superfície corporal queimada foi de 10% (3% - 22%). O Abbreviated Burn Severity Index foi de 6 (4 - 7). Foi necessária ventilação mecânica em 60% dos pacientes, com duração mediana de 6 (3 - 16) dias. O tempo mediano de permanência na unidade foi de 17 (7 - 32) dias. A mortalidade global foi de 19,9%. A mortalidade bruta e a proporção padronizada de mortalidade diminuíram entre 1995 e 2018. A proporção padronizada de mortalidade global foi de 0,99. Necessidade de ventilação mecânica (RC 8,80; IC95% 5,68 - 13,62), idade mais avançada (RC 1,07 por ano; IC95% 1,06 - 1,09), área total de superfície corporal queimada (RC 1,05 por 1%; IC95% 1,03 - 1,08) e extensão de queimaduras de terceiro grau (RC 1,05 por 1%; IC95% 1,03 - 1,07) foram fatores de risco independentes para mortalidade. Conclusão: Necessidade de ventilação mecânica, idade mais avançada e extensão da queimadura foram fatores de risco independentes para mortalidade na população adulta de pacientes queimados no Uruguai.

Introducción: en el contexto de la pandemia de SARS-CoV-2, diferentes autores propusieron adaptaciones a máscaras de buceo comerciales (máscaras modificadas, MM) para proporcionar oxigenoterapia a pacientes con o sin presión positiva. Hasta la fecha, ninguno ha evaluado su desempeño como interfaz para la ventilación no invasiva (VNI) en el modo de soporte de presión inspiratoria (PSI). Objetivos: desarrollar una interfaz de VNI utilizando MM y evaluar su rendimiento en comparación con una máscara oronasal (MC) convencional. Métodos: las MM se adaptaron como interfaces VNI utilizando dos piezas creadas mediante impresión 3D. Se comparó su desempeño contra una MC en 10 voluntarios sanos en modo PSI (3 cmH2O) con dos niveles de presión positiva al final de la espiración (PEEP 4 y 8 cmH2O). Se compararon: fugas del sistema, frecuencia respiratoria, volumen corriente, oximetría de pulso, CO2 transcutáneo y comodidad. Resultados: con 4 cmH2O de PEEP no hubo diferencias significativas entre las máscaras en ninguna de las variables estudiadas. Con 8 cmH2O de PEEP, el uso de MM se asoció con un menor nivel de CO2tc (41,0±5,7 vs 43,5±8,1 mmHg; p=0,03) y un mayor confort (8,3±1,1 vs 6,5±1,4; p

Carbon dioxide (CO2) is sensed by cells and can trigger signals to modify gene expression in different tissues leading to changes in organismal functions. Despite accumulating evidence that several pathways in various organisms are responsive to CO2 elevation (hypercapnia), it has yet to be elucidated how hypercapnia activates genes and signaling pathways, or whether they interact, are integrated, or are conserved across species. Here, we performed a large-scale transcriptomic study to explore the interaction/integration/conservation of hypercapnia-induced genomic responses in mammals (mice and humans) as well as invertebrates (Caenorhabditis elegans and Drosophila melanogaster). We found that hypercapnia activated genes that regulate Wnt signaling in mouse lungs and skeletal muscles in vivo and in several cell lines of different tissue origin. Hypercapnia-responsive Wnt pathway homologues were similarly observed in secondary analysis of available transcriptomic datasets of hypercapnia in a human bronchial cell line, flies and nematodes. Our data suggest the evolutionarily conserved role of high CO2 in regulating Wnt pathway genes.

Resumen La atrofia y la debilidad de los musculos respiratorios y perifericos son un problema frecuente en las Unidades de Cuidados Intensivos (UCI). Su diagnostico es dificultoso, especialmente en las primeras etapas de la enfermedad critica. Esto determina que en muchos casos no sea detectada hasta etapas avanzadas, por ejemplo, frente a dificultad para la desvinculacion de la asistencia ventilatoria mecanica. El objetivo de esta revision es describir las principales herramientas con las que contamos actualmente para la evaluacion muscular en la UCI, tanto periferica como respiratoria. Se mencionan tecnicas con distinto grado de complejidad y especificidad, haciendo particular hincapie en aquellas con mayor aplicabilidad en la practica clinica diaria, como la ecografia.

Atrophy and weakness of the respiratory and peripheral muscles is a common problem in the intensive care unit (ICU). It is difficult to diagnose, particularly in the early stages of critical disease. Consequently, many cases are detected only in advanced stages, for example, when difficulties in mechanical ventilation weaning are encountered. The aim of this review is to describe the main tools that are currently available for evaluation of peripheral and respiratory muscles in the ICU. Techniques of varying complexity and specificity are discussed, and particular emphasis is placed on those with greater relevance in daily clinical practice, such as ultrasound.

Resumen: Introducción: la mortalidad de los pacientes con injuria térmica ha descendido a nivel mundial. Este hecho se ha relacionado en parte con la creación de centros especializados en el tratamiento de esta patología. En nuestro medio no existen estudios recientes que evalúen la evolución de la mortalidad en este tipo de centros. Objetivo: describir las características de la población asistida y la evolución de la mortalidad en el Centro Nacional de Quemados. Material y método: estudio transversal, observacional, descriptivo. Se incluyeron todos los pacientes ingresados con diagnóstico de quemadura cutánea o de injuria inhalatoria desde la inauguración del centro en 1995 hasta el 31 de diciembre de 2017. Resultados: ingresaron en el período de estudio 3.050 pacientes quemados, 25% presentaron una superficie corporal quemada superior o igual a 20%. Existió un predominio de pacientes jóvenes (más de 60% menores de 50 años) y de sexo masculino (62%). El agente causal más frecuente fue el fuego directo (71%), seguido por líquidos calientes (9%) y electricidad (5%). El 43% de los pacientes requirió asistencia ventilatoria mecánica, y la estadía media en el centro fue de 17 días. La mortalidad global fue de 19,7%, similar a la esperada de acuerdo a scores de severidad específicos. La mortalidad de los pacientes más graves ha descendido desde la apertura del centro. Conclusiones: nuestro centro asiste predominantemente a pacientes jóvenes, con siniestros que involucran al fuego como el principal agente causal. La mortalidad es acorde a la esperada de acuerdo a los scores de severidad, destacándose un descenso continuo de la misma a lo largo de los años. Abstract: Introduction: burned patients mortality has decreased because of a better understanding of initial shock pathophysiology, early surgical interventions, antibiotic therapy optimization and appropriate nutritional support. Mortality reduction has also been related to the creation of specialized burn centers. There are no recent reports of burn injury patients in our country. Objective: to describe characteristics and evolution of patients assisted at the national burned center (Centro Nacional de Quemados, Uruguay). Methods: transversal, observational, descriptive study. All patients admitted in the center with diagnosis of skin burns or inhalation injury, from the center’s opening in 1995 through December 31, 2017. Results: during the study period 3,050-burned patients were admitted, 25% of which had a total body surface area burnt of at least 20%. There was a predominance of male sex (62%) and young patients (more than 60% had less than 50 years old). The most frequent responsible agent was direct fire (71%), followed by hot liquids (9%) and electricity (5%). Mechanical ventilation was needed in 43% of the patients, and mean length of stay in the center was 17 days. Overall mortality rate was 19.7%, accordingly to that predicted by specific severity scores. In the sub-group of more severe patients, mortality has progressively decreased since the center opening. Conclusions: our center assists young patients with burn injuries mostly caused by direct fire. Overall mortality is in line with the expected according to severity scores, having decreased progressively since the center inauguration. Resumo: Introdução: a mortalidade dos pacientes com injúria térmica tem diminuído em todo o mundo devido, em parte, à criação de centros especializados no tratamento desta patologia. No nosso meio não existem estudos recentes que avaliem a evolução da mortalidade neste tipo de centro. Objetivo: descrever as características da população atendida e a evolução da mortalidade no Centro Nacional de Quemados. Métodos: estudo transversal, observacional, descritivo. Foram incluídos todos os pacientes admitidos com diagnóstico de queimadura cutânea ou de injúria inalatória desde a inauguração do Centro em 1995 até o dia 31 de dezembro de 2017. Resultados: no período estudado, foram admitidos 3050 pacientes queimados, 25% apresentaram uma superfície corporal queimada maior ou igual a 20%. Observou-se o predomínio de pacientes jovens (mais de 60% com menos de 50 anos) e de sexo masculino (62%). O agente causal mais frequente foi o fogo direto (71%), seguido por líquidos quentes (9%) e eletricidade (5%). 43% dos pacientes necessitaram assistência ventilatória mecânica, e a permanência média no Centro foi de 17 dias. A mortalidade global foi de 19,7%, similar à esperada de acordo com os graus específicos de gravidade. A mortalidade dos pacientes mais graves vem diminuindo desde a abertura do centro. Conclusões: nosso centro atende predominantemente pacientes jovem sendo o fogo o principal agente causal. A mortalidade é similar à esperada de acordo com os graus específicos de gravidade, destacando-se um descenso continuo da mesma ao longo dos anos.

Delayed lung repair leads to alveolopleural fistulae, which are a major cause of morbidity after lung resections. We have reported that intrapleural hypercapnia is associated with delayed lung repair after lung resection. Here, we provide new evidence that hypercapnia delays wound closure of both large airway and alveolar epithelial cell monolayers because of inhibition of epithelial cell migration. Cell migration and airway epithelial wound closure were dependent on Rac1-GTPase activation, which was suppressed by hypercapnia directly through the upregulation of AMP kinase and indirectly through inhibition of injury-induced NF-κB-mediated CXCL12 (pleural CXC motif chemokine 12) release, respectively. Both these pathways were independently suppressed, because dominant negative AMP kinase rescued the effects of hypercapnia on Rac1-GTPase in uninjured resting cells, whereas proteasomal inhibition reversed the NF-κB-mediated CXCL12 release during injury. Constitutive overexpression of Rac1-GTPase rescued the effects of hypercapnia on both pathways as well as on wound healing. Similarly, exogenous recombinant CXCL12 reversed the effects of hypercapnia through Rac1-GTPase activation by its receptor, CXCR4. Moreover, CXCL12 transgenic murine recipients of orthotopic tracheal transplantation were protected from hypercapnia-induced inhibition of tracheal epithelial cell migration and wound repair. In patients undergoing lobectomy, we found inverse correlation between intrapleural carbon dioxide and pleural CXCL12 levels as well as between CXCL12 levels and alveolopleural leak. Accordingly, we provide first evidence that high carbon dioxide levels impair lung repair by inhibiting epithelial cell migration through two distinct pathways, which can be restored by recombinant CXCL12.

Muscle dysfunction is common in patients with adult respiratory distress syndrome and is associated with morbidity that can persist for years after discharge. In a mouse model of severe influenza A pneumonia, we found the proinflammatory cytokine IL-6 was necessary for the development of muscle dysfunction. Treatment with a Food and Drug Administration–approved Ab antagonist to the IL-6R (tocilizumab) attenuated the severity of influenza A–induced muscle dysfunction. In cultured myotubes, IL-6 promoted muscle degradation via JAK/STAT, FOXO3a, and atrogin-1 upregulation. Consistent with these findings, atrogin-1+/− and atrogin-1−/− mice had attenuated muscle dysfunction following influenza infection. Our data suggest that inflammatory endocrine signals originating from the injured lung activate signaling pathways in the muscle that induce dysfunction. Inhibiting these pathways may limit morbidity in patients with influenza A pneumonia and adult respiratory distress syndrome.

El propofol es un anestésico ampliamente utilizado en las unidades de cuidados intensivos. Su empleo puede provocar un efecto adverso poco frecuente pero extremadamente grave, conocido como síndrome por infusión de propofol (SIP), caracterizado por inestabilidad hemodinámica, rabdomiólisis, acidosis láctica y disfunción multiorgánica. Presentamos un caso de SIP con desenlace fatal, discutiendo su fisiopatología, clínica y consideraciones a tener en cuenta al emplear propofol.

RESUMO Resumo: Determinar os fatores independentes de risco associados com mortalidade em pacientes queimados adultos. Metodos: Estudo observacional retrospectivo, conduzido no Centro Nacional de Queimados do Uruguai. Incluiram-se todos os pacientes com queimaduras da pele admitidos a unidade desde sua inauguracao em 1° de julho de 1995 ate o dia 31 de dezembro de 2018. Estudaram-se os dados demograficos, perfis de queimadura, tempo de permanencia, duracao da ventilacao mecânica e mortalidade hospitalar. Utilizou-se regressao logistica multivariada para identificacao dos fatores de risco para mortalidade. A proporcao padronizada de mortalidade foi calculada pela divisao do numero de obitos observados pelo numero de obitos previstos, segundo o Abbreviated Burn Severity Index. Resultados: Durante o periodo do estudo, incluimos 3.112 pacientes. A mediana da area total de superficie corporal queimada foi de 10% (3% - 22%). O Abbreviated Burn Severity Index foi de 6 (4 - 7). Foi necessaria ventilacao mecânica em 60% dos pacientes, com duracao mediana de 6 (3 - 16) dias. O tempo mediano de permanencia na unidade foi de 17 (7 - 32) dias. A mortalidade global foi de 19,9%. A mortalidade bruta e a proporcao padronizada de mortalidade diminuiram entre 1995 e 2018. A proporcao padronizada de mortalidade global foi de 0,99. Necessidade de ventilacao mecânica (RC 8,80; IC95% 5,68 - 13,62), idade mais avancada (RC 1,07 por ano; IC95% 1,06 - 1,09), area total de superficie corporal queimada (RC 1,05 por 1%; IC95% 1,03 - 1,08) e extensao de queimaduras de terceiro grau (RC 1,05 por 1%; IC95% 1,03 - 1,07) foram fatores de risco independentes para mortalidade. Conclusao: Necessidade de ventilacao mecânica, idade mais avancada e extensao da queimadura foram fatores de risco independentes para mortalidade na populacao adulta de pacientes queimados no Uruguai.

Atrophy and weakness of the respiratory and peripheral muscles is a common problem in the intensive care unit (ICU). It is difficult to diagnose, particularly in the early stages of critical disease. Consequently, many cases are detected only in advanced stages, for example, when difficulties in mechanical ventilation weaning are encountered. The aim of this review is to describe the main tools that are currently available for evaluation of peripheral and respiratory muscles in the ICU. Techniques of varying complexity and specificity are discussed, and particular emphasis is placed on those with greater relevance in daily clinical practice, such as ultrasound.

Severe acute respiratory distress syndrome (ARDS) presents typically with an initializing event, followed by the need for mechanical ventilation. Most animal models of ALI are limited by the fact that they focus on a singular cause of acute lung injury (ALI) and therefore fail to mimic the complex, multifactorial pathobiology of ARDS. To better capture this scenario, we provide a comprehensive characterization of models of ALI combining two injuries: intra tracheal (i.t.) instillation of LPS or hypochloric acid (HCl) followed by ventilator‐induced lung injury (VILI). We hypothesized, that mice pretreated with LPS or HCl prior to VILI and thus receiving a (“two‐hit injury”) will sustain a superadditive lung injury when compared to VILI. Mice were allocated to following treatment groups: control with i.t. NaCl, ventilation with low peak inspiratory pressure (PIP), i.t. HCl, i.t. LPS, VILI (high PIP), HCl i.t. followed by VILI and LPS i.t. followed by VILI. Severity of injury was determined by protein content and MPO activity in bronchoalveolar lavage (BAL), the expression of inflammatory cytokines and histopathology. Mice subjected to VILI after HCl or LPS instillation displayed augmented lung injury, compared to singular lung injury. However, mice that received i.t. LPS prior to VILI showed significantly increased inflammatory lung injury compared to animals that underwent i.t. HCl followed by VILI. The two‐hit lung injury models described, resulting in additive but differential acute lung injury recaptures the clinical relevant multifactorial etiology of ALI and could be a valuable tool in translational research.

Objective: During clinical practice, it can be challenging, given the lack of response biomarkers, to identify the patients with metastatic breast cancer (mbca) who would benefit most from the addition of bevacizumab to first-line standard chemotherapy. The aim of the present review was to summarize the relevant scientific evidence and to discuss the experience of a group of experts in using bevacizumab to treat mbca. Methods: A panel of 17 Spanish oncology experts met to discuss the literature and their experience in the use of bevacizumab as first-line treatment for mbca. During the meeting, discussions focused on three main issues: the profile of the patients who could benefit most from bevacizumab, the optimal bevacizumab treatment duration, and the safety profile of bevacizumab. Results: The subset of mbca patients who would benefit the most from the addition of bevacizumab to first-line standard chemotherapy are those with clinically defined aggressive disease. Treatment with bevacizumab should be maintained until disease progression or the appearance of unacceptable toxicity. In the mbca setting, the toxicity profile of bevacizumab is well known and can be managed in clinical practice after adequate training. Conclusions: This expert group recommends administering bevacizumab as first-line treatment in patients with clinically aggressive disease.

The elevation of carbon dioxide (CO(2)) in tissues and the bloodstream (hypercapnia) occurs in patients with severe lung diseases, including chronic obstructive pulmonary disease (COPD). Whereas hypercapnia has been recognized as a marker of COPD severity, a role for hypercapnia in disease pathogenesis remains unclear. We provide evidence that CO(2) acts as a signaling molecule in mouse and human airway smooth muscle cells. High CO(2) activated calcium-calpain signaling and consequent smooth muscle cell contraction in mouse airway smooth muscle cells. The signaling was mediated by caspase-7-induced down-regulation of the microRNA-133a (miR-133a) and consequent up-regulation of Ras homolog family member A and myosin light-chain phosphorylation. Exposure of wild-type, but not caspase-7-null, mice to hypercapnia increased airway contraction and resistance. Deletion of the Caspase-7 gene prevented hypercapnia-induced airway contractility, which was restored by lentiviral transfection of a miR-133a antagonist. In a cohort of patients with severe COPD, hypercapnic patients had higher airway resistance, which improved after correction of hypercapnia. Our data suggest a specific molecular mechanism by which the development of hypercapnia may drive COPD pathogenesis and progression.

Los pacientes esplenectomizados poseen un riesgo aumentado de sufrir infecciones invasivas por microorganismos encapsulados como Streptococcus pneumoniae. La asociación de neumonía, meningitis y endocarditis causada por Streptococcus pneumoniae constituye un cuadro muy poco frecuente en la actualidad conocido como síndrome de Austrian. Ambas representan entidades extremadamente graves y con elevada mortalidad. El diagnóstico precoz y comienzo inmediato del tratamiento intensivo y multidisciplinario son factores claves para el pronóstico de los pacientes. Presentamos un caso de enfermedad neumocóccica invasiva en un paciente esplenectomizado, discutiendo algunos de los aspectos más importantes para la prevención y el tratamiento de estos cuadros.

Resumen El cancer de mama es la neoplasia mas frecuente en la mujer, siendo su etiologia desconocida y probablemente relacionada con multiples factores. Suele presentarse como masa, siendo imprescindible realizar una prueba de imagen mamaria y biopsiar las lesiones sospechosas. En los estadios precoces o localmente avanzados, el tratamiento incluye la cirugia (conservadora si es posible) seguida de tratamiento adyuvante: radioterapia (si cirugia conservadora y/o afectacion ganglionar), quimioterapia si se considera indicada (en ocasiones como tratamiento sistemico primario), trastuzumab (tumores HER2 positivos) y hormonoterapia (tumores con sobreexpresion de receptores hormonales). En caso de existir metastasis a distancia los objetivos principales del tratamiento son el mantenimiento de la calidad de vida y el aumento de la supervivencia. En funcion de las caracteristicas del tumor y de la localizacion de las metastasis, pueden utilizarse tratamientos sistemicos (hormonoterapia, quimioterapia y agentes biologicos) combinados o no con tratamientos locales como la cirugia y la radioterapia.

Resumen Los microARN (miRs) son pequenas moleculas de ARN no codificante capaces de regular negativamente la expresion genica. Participan activamente en la modulacion de importantes procesos celulares fisiologicos y estan involucrados en la patogenia de enfermedades pulmonares tales como el cancer de pulmon, la fibrosis pulmonar, el asma y la enfermedad pulmonar obstructiva cronica. Un mayor conocimiento del papel que los miRs desarrollan en estas patologias podria abrir las puertas a nuevas herramientas diagnosticas y terapeuticas. En esta revision, repasamos el rol que algunos miRs desempenan en la patogenia de ciertas enfermedades pulmonares, asi como la posible proyeccion de estos descubrimientos hacia la aplicacion clinica.

La intoxicación por bloqueadores de los canales de calcio puede dar lugar a un cuadro extremadamente grave. Presentamos el caso de un paciente con intoxicación severa por diltiazem que desarrolló un profundo estado de shock y disfunción multiorgánica. La inestabilidad hemodinámica puede ser refractaria a las medidas terapéuticas habituales, requiriendo la implementación de tratamientos coadyuvantes para sostener las funciones vitales. Analizamos la presentación clínica y fisiopatología de la intoxicación por calcio antagonistas. Finalmente, presentamos las alternativas terapéuticas en base a la evidencia actual.

Adenosine triphosphate (ATP) is released by alveolar epithelial cells during ventilator-induced lung injury (VILI) and regulates fluid transport across epithelia. High CO(2) levels are observed in patients with "permissive hypercapnia," which inhibits alveolar fluid reabsorption (AFR) in alveolar epithelial cells. The authors set out to determine whether VILI affects AFR and whether the purinergic pathway is modulated in cells exposed to hypercapnia. Control group was compared against VILI (tidal volume [Vt] = 35 mL/kg, zero positive end-expiratory pressure [PEEP]) and protective ventilation (Vt = 6 mL/kg, PEEP = 10 cm H(2)O) groups. Lung mechanics, histology, and AFR were evaluated. Alveolar epithelial cells (AECs) were loaded with Fura 2-AM to measure intracellular calcium in the presence ATP (10 μM) at 5% or 10% CO(2) as compared with baseline. High tidal volume ventilation impairs lung mechanics and AFR. Hypercapnia (HC) increases intracellular calcium levels in response to ATP stimulation. HC + ATP is the most detrimental combination decreasing AFR. Purinergic signaling in AECs is modulated by high CO(2) levels via increased cytosolic calcium. The authors reason that this modulation may play a role in the impairment of alveolar epithelial functions induced by hypercapnia.

Resumen Introduccion Las enfermedades con obstruccion cronica de la via aerea, como la enfermedad pulmonar obstructiva cronica, asocian alteraciones funcionales de los musculos respiratorios. Los agonistas adrenergicos β 2 mejoran la fuerza muscular en condiciones fisiologicas y patologicas. Nuestro objetivo ha sido estudiar los efectos del salbutamol sobre la contractilidad diafragmatica en un modelo animal de obstruccion cronica de la via aerea lograda por obstruccion traqueal (OT) extrinseca. Materiales y metodos Se aleatorizaron 24 ratas Sprague-Dawley en 4 grupos: a) control; b) OT; c) OT+salbutamol agudo, y d) OT+salbutamol cronico. Se estudiaron los gases sanguineos, el equilibrio acido-base y la fuerza diafragmatica in vitro, a traves de las siguientes medidas: tension maxima (T max ), tiempo de contraccion (TC), velocidad de contraccion (dT/dt max ), tiempo de relajacion media (TR 1/2 ), velocidad de relajacion (−dT/dt max ) y curvas fuerza-frecuencia. Resultados Los 3 grupos sometidos a OT presentaron una disminucion significativa del pH y un incremento de la presion arterial de anhidrido carbonico y del bicarbonato en sangre arterial (p max , de dT/dt max y de la curva fuerza-frecuencia en comparacion con los otros grupos (p max fue mayor en el grupo OT+salbutamol cronico comparado con el grupo OT (p max fueron: control, 6,46±0,90 N/cm 2 ; OT, 3,28±0,55 N/cm 2 ; OT+salbutamol agudo, 6,18±0,71 N/cm 2 ; OT+salbutamol cronico, 7,09±0,59 N/cm 2 . Conclusiones La disfuncion diafragmatica asociada a obstruccion cronica de la via aerea mejora con salbutamol administrado tanto en forma aguda como cronica. Los mecanismos involucrados en la disfuncion muscular deben analizarse mas profundamente.

Chronic airflow obstruction in conditions such as chronic obstructive pulmonary disease is associated with respiratory muscle dysfunction. Our aim was to study the effects of salbutamol-a beta-adrenergic agonist known to improve muscle strength in physiologic and pathologic conditions-on diaphragm contractility in an animal model of chronic airway obstruction achieved by tracheal banding.Twenty-four Sprague-Dawley rats were randomized into a control group and 3 tracheal banding groups, 1 that received acute salbutamol treatment, 1 that received chronic salbutamol treatment, and 1 that received nothing. Arterial blood gases, acid-base balance, and in vitro diaphragmatic contractility were evaluated by measuring peak twitch tension, contraction time, contraction velocity, half-relaxation time, relaxation velocity, and force-frequency curves.The 3 study groups had significantly reduced arterial pH and increased PaCO2 and bicarbonate levels compared to the control group (P.05). The untreated tracheal banding group had significantly reduced peak twitch tension and contraction velocity, and a significantly lower force-frequency curve in comparison with the other groups (P.05). The chronic treatment group had a higher relaxation velocity than the untreated study group (P.05). The mean (SE) peak twitch tension values were 6.46 (0.90)N/cm(2) for the control group, 3.28 (0.55)N/cm(2) for the untreated tracheal banding group, 6.18 (0.71)N/cm(2) for the acute treatment group, and 7.09 (0.59)N/cm(2) for the chronic treatment group.Diaphragmatic dysfunction associated with chronic airflow obstruction improves with both the acute and chronic administration of salbutamol. The mechanisms involved in respiratory muscle dysfunction warrant further study.

Objetivo: La sepsis grave se acompa?a en un alto porcentaje de casos de insuficiencia respiratoria aguda, donde la debilidad de los m?sculos respiratorios desempe?a un papel importante. Los m?sculos respiratorios debilitados y sometidos a una carga mec?nica aumentada pueden evolucionar a fatiga muscular con agravamiento de la insuficiencia respiratoria. Los f?rmacos adren?rgicos ?2, al mejorar la fuerza de contracci?n muscular, podr?an ser de utilidad en la prevenci?n y el manejo de la insuficiencia respiratoria de pacientes con sepsis. El objetivo de este trabajo ha sido estudiar los efectos del salbutamol en la funci?n diafragm?tica en un modelo animal de sepsis peritoneal. Material y m?todos: Se estudiaron 3 grupos de animales: a) grupo control (n = 7), al que se realiz? laparotom?a mediana sin abordaje visceral; b) grupo sepsis (n = 10), al que se indujo sepsis peritoneal por ligadura y punci?n cecal (LPC), y c) grupo salbutamol (n = 7), en el que la sepsis peritoneal se trat? con salbutamol (LPC + salbutamol). Los par?metros hemodin?micos y los gases sangu?neos se midieron in vivo. La funci?n diafragm?tica se evalu? in vitro. Resultados: El salbutamol aument? el flujo a?rtico y la frecuencia card?aca a la vez que disminuy? la presi?n arterial media en la sepsis peritoneal (p < 0,05). La sepsis determin? una ca?da significativa de la fuerza diafragm?tica tanto antes como despu?s de un protocolo de fatiga muscular. El tratamiento con salbutamol mejor? la fuerza de contracci?n muscular en ambos casos (p < 0,05). Conclusiones: El uso de agentes adren?rgicos ?2 como el salbutamol mejora la funci?n diafragm?tica durante la sepsis experimental. Los mecanismos de esta mejor?a deben estudiarse en mayor profundidad.

Introduction: This was a cross-sectional multicenter study to investigate the ability of physicians and nurses from three different countries to subjectively evaluate sublingual microcirculation images and thereby discriminate normal from abnormal sublingual microcirculation based on flow and density abnormalities. Methods: Forty-five physicians and 61 nurses (mean age, 36 +/- 10 years; 44 males) from three different centers in The Netherlands (n = 61), Uruguay (n = 12), and Japan (n = 33) were asked to subjectively evaluate a sample of 15 microcirculation videos randomly selected from an experimental model of endotoxic shock in pigs. All videos were first analyzed offline using the A.V.A. software by an independent, experienced investigator and were categorized as good, bad, or very bad microcirculation based on the microvascular flow index, perfused capillary density, and proportion of perfused capillaries. Then, the videos were randomly assigned to the examiners, who were instructed to subjectively categorize each image as good, bad, or very bad. An interrater analysis was performed, and sensitivity and specificity tests were calculated to evaluate the proportion of A.V.A. score abnormalities that the examiners correctly identified. Results: The kappa statistics indicated moderate agreement in the evaluation of microcirculation abnormalities using three categories, i.e., good, bad, or very bad (kappa = 0.48), and substantial agreement using two categories, i.e., normal (good) and abnormal (bad or very bad) (kappa = 0.66). There was no significant difference between the kappa three and kappa two statistics. We found that the examiner's subjective evaluations had good diagnostic performance and were highly sensitive (84%; 95% confidence interval, 81%-86%) and specific (87%; 95% confidence interval, 84%-90%) for sublingual microcirculatory abnormalities as assessed using the A.V.A. software. Conclusions: The subjective evaluations of sublingual microcirculation by physicians and nurses agreed well with a conventional offline analysis and were highly sensitive and specific for sublingual microcirculatory abnormalities.

In patients with acute respiratory distress syndrome (ARDS) hypercapnia is a marker of poor prognosis, however there is controversial information regarding the effect of hypercapnia on outcomes. Recently two studies in a large population of mechanical ventilation patients showed higher mortality associated independently to hypercapnia. Key roles responsible for the poor clinical outcomes observed in critically ill patients exposed to hypercapnia are not well known, two possible mechanisms involved are the effect of CO2 on the muscle and the alveolar epithelium. Hypercapnia frequently coexists with muscle atrophy and dysfunction, moreover patients surviving ARDS present reduced muscle strength and decreased physical quality of life. One of the possible mechanisms responsible for these abnormalities could be the effects of hypercapnia during the course of ARDS. More over controversy persists about the hypercapnia role in the alveolar space, in the last years there is abundant experimental information on its deleterious effects on essential functions of the alveolar epithelium.

Este Trabajo Final de Máster (TFM) pretende realizar primero un análisis retrospectivo, basado en el analizar los efectos de las ayudas acopladas y desacotadas de la PAC en distintos sistemas agrarios de la PAC en los últimos 10 años en determinadas comarcas de Castilla León, con objeto de valorar como éstas han afectado a la rentabilidad de explotaciones, al uso de inputs agrarios o al cambio de estructura de la misma (tamaño, sistema de tenencia etc...), Departamento de Ingeniería Agrícola y Forestal, Máster en Ingeniería Agronómica