Aida Venado

Alcohol ingestion disrupts alveolar epithelial barrier function by activation of macrophage-derived transforming growth factor beta1.

BackgroundChronic alcohol abuse causes oxidative stress and impairs alveolar epithelial barrier integrity, thereby rendering the lung susceptible to acute edematous injury. Experimentally, alcohol-induced oxidative stress increases the expression of transforming growth factor β1 (TGFβ1) in the lung; however, we do not know the precise contribution of various alveolar cells in this process. In the present study, we focused on cell-cell interactions between alveolar macrophages and epithelial cells and the potential mechanisms by which TGFβ1 may become activated in the alveolar space of the alcoholic lung.MethodsPrimary alveolar macrophages and epithelial cells were isolated from control- and alcohol-fed Sprague–Dawley rats. Expression of TGFβ1 and the epithelial integrin αvβ6 were examined by real time PCR and either immunocytochemistry or flow cytometry. Alveolar epithelial cells were cultured on transwell supports in the presence of macrophage cell lysate from control- or alcohol-fed rats or in the presence of viable macrophages ± alcohol. Epithelial barrier function was assessed by transepithelial resistance (TER) and paracellular flux of Texas Red dextran.ResultsTGFβ1 expression was increased in alveolar macrophages from alcohol-fed rats, and TGFβ1 protein was predominantly membrane-bound. Importantly, alveolar macrophage cellular lysate from alcohol-fed rats decreased TER and increased paracellular dextran flux in primary alveolar epithelial cell monolayers as compared to the lysates from control-fed rats. Alcohol-induced epithelial barrier dysfunction was prevented by anti-TGFβ1 antibody treatment, indicating the presence of bioactive TGFβ1 in the macrophage lysate. In addition, co-culturing macrophages and epithelial cells in the presence of alcohol decreased epithelial barrier function, which also was prevented by anti-TGFβ1 and anti-αvβ6 treatment. In parallel, chronic alcohol ingestion in vivo, or direct treatment with active TGFβ1 in vitro, increased the expression of αvβ6 integrin, which is known to activate TGFβ1, in alveolar epithelial cells.ConclusionsTaken together, these data suggest that interactions between alveolar epithelial cells and macrophages contribute to the alcohol-mediated disruption of epithelial barrier function via the expression and activation of TGFβ1 at points of cell-cell contact.

Prolonged Extracorporeal Membrane Oxygenation Use as a Bridge to Lung Transplantation: It Is Time for a National Registry

Correspondence Although we cited reference 30 (cited here as reference 2) under Subjects in the Materials and Methods section, it might have been better to also cite it under Estimation of Sleep Duration in the Materials and Methods section. Altogether, we believed that the use of the actigraph along with the diary for the purpose of the two studies would be superior to the use of only a sleep diary. As Dr Kawada mentioned, sleep duration was a key factor in this study, 1 and the participants wore the actigraph for 7 days so we could measure the mean daily sleep duration. An actigraph (Actiwatch AW-Light; Mini Mitter or Koninklijke Philips Electronics NV) has been used in many reports. We believed that the use of the actigraph as described here was suitable for this study. We appreciate the comments of Dr Kawada. They enabled us to provide details of our method for calculating sleep duration that were only briefl y provided in our article. 1

Frailty phenotypes and mortality after lung transplantation: A prospective cohort study

Frailty is associated with increased mortality among lung transplant candidates. We sought to determine the association between frailty, as measured by the Short Physical Performance Battery (SPPB), and mortality after lung transplantation. In a multicenter prospective cohort study of adults who underwent lung transplantation, preoperative frailty was assessed with the SPPB (n = 318) and, in a secondary analysis, the Fried Frailty Phenotype (FFP; n = 299). We tested the association between preoperative frailty and mortality following lung transplantation with propensity score–adjusted Cox models. We calculated postestimation marginalized standardized risks for 1‐year mortality by frailty status using multivariate logistic regression. SPPB frailty was associated with an increased risk of both 1‐ and 4‐year mortality (adjusted hazard ratio [aHR]: 7.5; 95% confidence interval [CI]: 1.6‐36.0 and aHR 3.8; 95%CI: 1.8‐8.0, respectively). Each 1‐point worsening in SPPB was associated with a 20% increased risk of death (aHR: 1.20; 95%CI: 1.08‐1.33). Frail subjects had an absolute increased risk of death within the first year after transplantation of 12.2% (95%CI: 3.1%‐21%). In secondary analyses, FFP frailty was associated with increased risk of death within the first postoperative year (aHR: 3.8; 95%CI: 1.1‐13.2) but not over longer follow‐up. Preoperative frailty is associated with an increased risk of death after lung transplantation.

Unexplained hemolysis in patients undergoing ECMO: beware of hypertriglyceridemia

Hemolysis is a common complication of extracorporeal membrane oxygenation (ECMO) support and is associated with increased mortality. Frequent monitoring of markers of hemolysis is performed at ECMO centers. We report two cases of spurious hemolysis caused by hypertriglyceridemia in patients undergoing ECMO support. Critically ill patients, including those receiving ECMO, may be at risk of developing medication-induced hypertriglyceridemia. The interference of lipids with the measurement of plasma free hemoglobin, a marker of hemolysis, should be recognized. Our cases highlight the importance of investigating hypertriglyceridemia as part of the assessment of unexplained hemolysis in patients supported with ECMO.

Unexpected Swallowing of a Knife

A 30-year-old woman with a history of bulimia presented to the emergency department after swallowing a knife. She inserted the knife into the posterior oropharynx to demonstrate to her companions that she no longer had a gag reflex.