Factors affecting early and long-term outcomes after completion pneumonectomy

Objective: To identify factors that affect operative mortality and morbidity and long-term survival after completion pneumonectomy. Methods: We retrospectively reviewed the charts of consecutive patients who underwent completion pneumonectomy at our cardiothoracic surgery department from January 1996 to December 2005. Results: We identified 69 patients, who accounted for 17.8% of all pneumonectomies during the study period; 22 had benign disease and 47 malignant disease (second primary lung cancer, n = 19; local recurrence, n = 17; or metastasis, n = 11). There were 50 males and 19 females with a mean age of 60 years (range, 29–80 years). Postoperative mortality was 12% and postoperative morbidity 41%. Factors associated with postoperative mortality included obesity (p = 0.005), coronary artery disease (p = 0.03), removal of the right lung (p = 0.02), advanced age (p = 0.02), and renal failure (p < 0.0001). Preoperative renal failure was the only significant risk factor for mortality by multivariate analysis (p = 0.036). Bronchopleural fistula developed in seven patients (10%), with risk factors being removal of the right lung (p = 0.04) and mechanical stump closure (p = 0.03). Overall survival was 65% after 3 years and 46% after 5 years. Long-term survival was not affected by the reason for completion pneumonectomy. Conclusion: Although long-term survival was acceptable, postoperative mortality and morbidity rates remained high, confirming the reputation of completion pneumonectomy as a challenging procedure. Significant comorbidities and removal of the right lung were the main risk factors for postoperative mortality. Improved patient selection and better management of preoperative renal failure may improve the postoperative outcomes of this procedure, which offers a chance for prolonged survival.     

GRADE guidelines: 13. Preparing Summary of Findings tables and evidence profiles—continuous outcomes

Presenting continuous outcomes in Summary of Findings tables presents particular challenges to interpretation. When each study uses the same outcome measure, and the units of that measure are intuitively interpretable (e.g., duration of hospitalization, duration of symptoms), presenting differences in means is usually desirable. When the natural units of the outcome measure are not easily interpretable, choosing a threshold to create a binary outcome and presenting relative and absolute effects become a more attractive alternative.When studies use different measures of the same construct, calculating summary measures requires converting to the same units of measurement for each study. The longest standing and most widely used approach is to divide the difference in means in each study by its standard deviation and present pooled results in standard deviation units (standardized mean difference). Disadvantages of this approach include vulnerability to varying degrees of heterogeneity in the underlying populations and difficulties in interpretation. Alternatives include presenting results in the units of the most popular or interpretable measure, converting to dichotomous measures and presenting relative and absolute effects, presenting the ratio of the means of intervention and control groups, and presenting the results in minimally important difference units. We outline the merits and limitations of each alternative and provide guidance for meta-analysts and guideline developers.     

Recovery and outcomes after the acute respiratory distress syndrome (ARDS) in patients and their family caregivers

Outcomes after acute respiratory distress syndrome (ARDS) are similar to those of other survivors of critical illness and largely affect the nerve, muscle, and central nervous system but also include a constellation of varied physical devastations ranging from contractures and frozen joints to tooth loss and cosmesis. Compromised quality of life is related to a spectrum of impairment of physical, social, emotional, and neurocognitive function and to a much lesser extent discrete pulmonary disability. Intensive care unit-acquired weakness (ICUAW) is ubiquitous and includes contributions from both critical illness polyneuropathy and myopathy, and recovery from these lesions may be incomplete at 5 years after ICU discharge. Cognitive impairment in ARDS survivors ranges from 70 to 100 % at hospital discharge, 46 to 80 % at 1 year, and 20 % at 5 years, and mood disorders including depression and post-traumatic stress disorder (PTSD) are also sustained and prevalent. Robust multidisciplinary and longitudinal interventions that improve these outcomes are still uncertain and data in our literature are conflicting. Studies are needed in family members of ARDS survivors to better understand long-term outcomes of the post-ICU family syndrome and to evaluate how it affects patient recovery.     

Melatonin modulates neonatal brain inflammation through endoplasmic reticulum stress,autophagy, and miR‐34a/silent information regulator 1 pathway

Maternal infection/inflammation represents one of the most important factors involved in the etiology of brain injury in newborns. We investigated the modulating effect of prenatal melatonin on the neonatal brain inflammation process resulting from maternal intraperitoneal (i.p.) lipopolysaccharide (LPS) injections. LPS (300 μg/kg) was administered to pregnant rats at gestational days 19 and 20. Melatonin (5 mg/kg) was administered i.p. at the same time as LPS. Melatonin counteracted the LPS sensitization to a second ibotenate‐induced excitotoxic insult performed on postnatal day (PND) 4. As melatonin succeeded in reducing microglial activation in neonatal brain at PND1, pathways previously implicated in brain inflammation regulation, such as endoplasmic reticulum (ER) stress, autophagy and silent information regulator 1 (SIRT1), a melatonin target, were assessed at the same time‐point in our experimental groups. Results showed that maternal LPS administrations resulted in an increase in CHOP and Hsp70 protein expression and eIF2α phosphorylation, indicative of activation of the unfolded protein response consequent to ER stress, and a slighter decrease in the autophagy process, determined by reduced lipidated LC3 and increased p62 expression. LPS‐induced inflammation also reduced brain SIRT1 expression and affected the expression of miR‐34a, miR146a, and miR‐126. All these effects were blocked by melatonin. Cleaved‐caspase‐3 apoptosis pathway did not seem to be implicated in the noxious effect of LPS on the PND1 brain. We conclude that melatonin is effective in reducing maternal LPS‐induced neonatal inflammation and related brain injury. Its role as a prophylactic/therapeutic drug deserves to be investigated by clinical studies.