Influence of Pretransplant Restrictive Lung Disease on Allogeneic Hematopoietic Cell Transplantation Outcomes

We conducted a 15-year retrospective cohort study to determine the prevalence of restrictive lung disease prior to allogeneic hematopoietic cell transplant (HCT), and to assess whether this was a risk factor for poor outcomes. 2545 patients were eligible for the analysis. Restrictive lung disease was defined as a total lung capacity (TLC) <80% of predicted normal. Chest x-rays and /or computed tomography scans were reviewed for all restricted patients to determine whether lung parenchymal abnormalities were unlikely or highly likely to cause restriction. Multivariate Cox-proportional hazard and sensitivity analyses were performed to assess the relationship between restriction and early respiratory failure and nonrelapse mortality. Restrictive lung disease was present in 194 subjects (7.6%) prior to transplantation. Among these cases, radiographically apparent abnormalities were unlikely to be the cause of the restriction in 149 (77%) subjects. In unadjusted and adjusted analyses, the presence of pulmonary restriction was significantly associated with a 2-fold increase in risk for early respiratory failure and nonrelapse mortality, suggesting that these outcomes occurring in the absence of radiographically apparent abnormalities may be related to respiratory muscle weakness. These findings suggest that pulmonary restriction should be considered as a risk factor for poor outcomes after transplant

Reflections Magazine of the Faculty of Education. Volume 3 No. 4 July 1991

La formación en el afecto, en los valores, en la moral... ¿Qué mejor ámbito para su análisis e incorporación a una práctica social y pedagógica coherente con ello que la vida cotidiana?...la vida cotidiana escolar o familiar, personal o colectiva. Los afectos, y éstos como fundamento de una educación orientada hacia la formación de sujetos históricos, hombres y mujeres con responsabilidad, compromiso y conciencia sociales, corresponden a una de las formas de contacto cotidiano más importantes, especialmente por la intensidad de los sentimientos que en ellas se establecen: nos referimos a las relaciones entre sujetos. Constituyen expresiones suyas, las relaciones de amistad, el amor, pero también el adío. Aunque una valoración de tales sentimientos solo se logra mediante el análisis del contenido y la motivación — sobre todo de orden moral— de tales sentimientos, podemos afirmar, en general, siguiendo a Agnes Heller que el desarrollo de la moral, de la política, del arte y de la ciencia, es inconcebible sin grandes amores y grandes odios’’.Training in affection, in values, in morality... What better environment for its analysis and incorporation into a coherent social and pedagogical practice than daily life?... daily school or family, personal life or collective. Affections, and these as the foundation of an education oriented towards the formation of historical subjects, men and women with social responsibility, commitment and conscience, correspond to one of the most important forms of daily contact, especially due to the intensity of the feelings that in they are established: we refer to the relations between subjects. Their expressions are friendships, love, but also goodbye. Although an assessment of such feelings can only be achieved through analysis of content and motivation — especially of moral order— of such feelings, we can affirm, in general, following Agnes Heller that the development of morality, politics, art and science is inconceivable without great loves and great hates.Modalidad Presencia

Global muscle dysfunction as a risk factor of readmission to hospital due to COPD exacerbations

Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with several modifiable (sedentary life-style, smoking, malnutrition, hypoxemia) and non-modifiable (age, co-morbidities, severity of pulmonary function, respiratory infections) risk factors. We hypothesise that most of these risk factors may have a converging and deleterious effects on both respiratory and peripheral muscle function in COPD patients. METHODS: A multicentre study was carried out in 121 COPD patients (92% males, 63 ± 11 yr, FEV(1), 49 ± 17%pred). Assessments included anthropometrics, lung function, body composition using bioelectrical impedance analysis (BIA), and global muscle function (peripheral muscle (dominant and non-dominant hand grip strength, HGS), inspiratory (PI(max)), and expiratory (PE(max)) muscle strength). GOLD stage, clinical status (stable vs. non-stable) and both current and past hospital admissions due to COPD exacerbations were included as covariates in the analyses. RESULTS: Respiratory and peripheral muscle weakness were observed in all subsets of patients. Muscle weakness, was significantly associated with both current and past hospitalisations. Patients with history of multiple admissions showed increased global muscle weakness after adjusting by FEV(1) (PE(max), OR = 6.8, p < 0.01; PI(max), OR = 2.9, p < 0.05; HGSd, OR = 2.4, and HGSnd, OR = 2.6, p = 0.05). Moreover, a significant increase in both respiratory and peripheral muscle weakness, after adjusting by FEV(1), was associated with current acute exacerbations. CONCLUSIONS: Muscle dysfunction, adjusted by GOLD stage, is associated with an increased risk of hospital admissions due to acute episodes of exacerbation of the disease. Current exacerbations further deteriorate muscle dysfunction.Sources of support: Supported in part by grants from “SEPAR-Area de Enfermeri´a y Fisioterapia” and BAE06/90061. CIBERES (Instituto de Salud Carlos III, Ministerio de Sanidad, Spain)

Sustained CTL activation by murine pulmonary epithelial cells promotes the development of COPD-like disease

Chronic obstructive pulmonary disease (COPD) is a lethal progressive lung disease culminating in permanent airway obstruction and alveolar enlargement. Previous studies suggest CTL involvement in COPD progression; however, their precise role remains unknown. Here, we investigated whether the CTL activation receptor NK cell group 2D (NKG2D) contributes to the development of COPD. Using primary murine lung epithelium isolated from mice chronically exposed to cigarette smoke and cultured epithelial cells exposed to cigarette smoke extract in vitro, we demonstrated induced expression of the NKG2D ligand retinoic acid early tran - script 1 (RAET1)as well as NKG2D-mediated cytotoxicity. Furthermore, a genetic model of inducible RAET1 expression on mouse pulmonary epithelial cells yielded a severe emphysematous phenotype characterized by epithelial apoptosis and increased CTL activation, which was reversed by blocking NKG2D activation. We also assessed whether NKG2D ligand expression corresponded with pulmonary disease in human patients by staining airway and peripheral lung tissues from never smokers, smokers with normal lung function, and current and former smokers with COPD. NKG2D ligand expression was independent of NKG2D receptor expression in COPD patients, demonstrating that ligand expression is the limiting factor in CTL activation. These results demonstrate that aberrant, persistent NKG2D ligand expression in the pulmonary epithelium contributes to the development of COPD pathologies

Mass of intercostal muscles associates with risk of multiple exacerbations in COPD

BACKGROUND: The potential role of decreased respiratory muscle mass, if any, in mediating the susceptibility to exacerbation in COPD patients has not been determined. We hypothesized that a decrease in respiratory muscle mass is associated with increased risk of multiple hospital admissions due to acute exacerbations of the disease. METHODS: Eligible cases and controls (n=20) were identified from records of our department's pulmonary clinic. Ten subjects diagnosed with COPD (males, 66+/-7yr, Body Mass Index (BMI)=26+/-4kg/m(2)) were identified as fragile patients. Fragility was defined as four or more admissions in the previous year due to severe exacerbations of the disease. Fragile patients were matched with 10 non-fragile controls, defined as COPD patients who had required only one admission due to exacerbation of the disease. Criteria for 1:1 matching included ethnicity, gender, age, BMI, degree of airflow obstruction (i.e., FEV(1)), comorbidity and chronic treatment. Multiple computed tomography (CT) scan slices were obtained to assess area and attenuation coefficients of multiple upper limb, thorax, abdomen and lower limb muscles. RESULTS: CSA of intercostal and abdominal muscles was significantly decreased in fragile COPD patients (right side intercostals, mean relative difference (MRD)=-14%, p=0.010; OR (95% CI)=2.2 (1.1-4.8), p=0.021; left side, MRD=-13%, p=0.007; OR=2.2 (1.1-4.5), p=0.027). CSA and attenuation coefficients of all other muscle compartments showed no statistical differences between the two study groups but showed the same trend. Strength of the inspiratory and expiratory muscles did not differ between the two study groups. CONCLUSIONS: This study shows that the risk for multiple admissions due to a COPD exacerbation associates with a marked decrease in the CSA of the intercostal muscle compartment.Grants from CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Spain; ARMAR, SEPAR and SOCAP fellowships; and Judith Garcia-Aymerich has a research contract from the Instituto de Salud Carlos III (CP05/00118), Ministry of Health, Spain

Sustained CTL activation by murine pulmonary epithelial cells promotes the development of COPD-like disease

Chronic obstructive pulmonary disease (COPD) is a lethal progressive lung disease culminating in permanent airway obstruction and alveolar enlargement. Previous studies suggest CTL involvement in COPD progression; however, their precise role remains unknown. Here, we investigated whether the CTL activation receptor NK cell group 2D (NKG2D) contributes to the development of COPD. Using primary murine lung epithelium isolated from mice chronically exposed to cigarette smoke and cultured epithelial cells exposed to cigarette smoke extract in vitro, we demonstrated induced expression of the NKG2D ligand retinoic acid early tran - script 1 (RAET1)as well as NKG2D-mediated cytotoxicity. Furthermore, a genetic model of inducible RAET1 expression on mouse pulmonary epithelial cells yielded a severe emphysematous phenotype characterized by epithelial apoptosis and increased CTL activation, which was reversed by blocking NKG2D activation. We also assessed whether NKG2D ligand expression corresponded with pulmonary disease in human patients by staining airway and peripheral lung tissues from never smokers, smokers with normal lung function, and current and former smokers with COPD. NKG2D ligand expression was independent of NKG2D receptor expression in COPD patients, demonstrating that ligand expression is the limiting factor in CTL activation. These results demonstrate that aberrant, persistent NKG2D ligand expression in the pulmonary epithelium contributes to the development of COPD pathologies

Sustained CTL activation by murine pulmonary epithelial cells promotes the development of COPD-like disease

Chronic obstructive pulmonary disease (COPD) is a lethal progressive lung disease culminating in permanent airway obstruction and alveolar enlargement. Previous studies suggest CTL involvement in COPD progression; however, their precise role remains unknown. Here, we investigated whether the CTL activation receptor NK cell group 2D (NKG2D) contributes to the development of COPD. Using primary murine lung epithelium isolated from mice chronically exposed to cigarette smoke and cultured epithelial cells exposed to cigarette smoke extract in vitro, we demonstrated induced expression of the NKG2D ligand retinoic acid early transcript 1 (RAET1) as well as NKG2D-mediated cytotoxicity. Furthermore, a genetic model of inducible RAET1 expression on mouse pulmonary epithelial cells yielded a severe emphysematous phenotype characterized by epithelial apoptosis and increased CTL activation, which was reversed by blocking NKG2D activation. We also assessed whether NKG2D ligand expression corresponded with pulmonary disease in human patients by staining airway and peripheral lung tissues from never smokers, smokers with normal lung function, and current and former smokers with COPD. NKG2D ligand expression was independent of NKG2D receptor expression in COPD patients, demonstrating that ligand expression is the limiting factor in CTL activation. These results demonstrate that aberrant, persistent NKG2D ligand expression in the pulmonary epithelium contributes to the development of COPD pathologies

Executive summary of the SEPAR recommendations for the diagnosis and treatment of non-small cell lung cancer

The Thoracic Surgery and Thoracic Oncology groups of the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) have backed the publication of a handbook on recommendations for the diagnosis and treatment of non-small cell lung cancer. Due to the high incidence and mortality of this disease, the best scientific evidence must be constantly updated and made available for consultation by healthcare professionals.To draw up these recommendations, we called on a wide-ranging group of experts from the different specialties, who have prepared a comprehensive review, divided into 4 main sections. The first addresses disease prevention and screening, including risk factors, the role of smoking cessation, and screening programs for early diagnosis. The second section analyzes clinical presentation, imaging studies, and surgical risk, including cardiological risk and the evaluation of respiratory function. The third section addresses cytohistological confirmation and staging studies, and scrutinizes the TNM and histological classifications, non-invasive and minimally invasive sampling methods, and surgical techniques for diagnosis and staging. The fourth and final section looks at different therapeutic aspects, such as the role of surgery, chemotherapy, radiation therapy, a multidisciplinary approach according to disease stage, and other specifically targeted treatments, concluding with recommendations on the follow-up of lung cancer patients and surgical and endoscopic palliative interventions in advanced stages. (C) 2016 SEPAR. Published by Elsevier Espana, S.L.U. All rights reserved

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries

Background: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide.Methods: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters.Results: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 percent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 percent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 percent; however, it was 41 per cent in low-to-middle-compared with 19 per cent in very high-HDI countries.Conclusion: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761)