Targeting IL-11 to reduce fibrocyte circulation and lung accumulation in animal models of pulmonary hypertension-associated lung fibrosis.

Background And Purpose: IL-11 is a member of the IL-6 family of cytokine initially considered as haematopoietic and cytoprotective factor. Recent evidence indicates that IL-11 promotes lung fibrosis and pulmonary hypertension in animal models and is elevated in lung tissue of patients with pulmonary fibrosis and pulmonary hypertension. Fibrocytes are bone marrow-derived circulating cells that participate in lung fibrosis and pulmonary hypertension, but the role of IL-11 on fibrocytes is unknown.

Targeting IL-11 system as a treatment of pulmonary arterial hypertension.

IL-11 is linked to fibrotic diseases, but its role in pulmonary hypertension is unclear. We examined IL-11's involvement in idiopathic pulmonary arterial hypertension (iPAH). Using samples from control (n = 20) and iPAH (n = 6) subjects, we assessed IL-11 and IL-11Rα expression and localization through RT-qPCR, ELISA, immunohistochemistry, and immunofluorescence.

IL-11 system participates in pulmonary artery remodeling and hypertension in pulmonary fibrosis.

Background: Pulmonary hypertension (PH) associated to idiopathic pulmonary fibrosis (IPF) portends a poor prognosis. IL-11 has been implicated in fibrotic diseases, but their role on pulmonary vessels is unknown. Here we analyzed the contribution of IL-11 to PH in patients with IPF and the potential mechanism implicated.

Predictive Value of Immune Cell Functional Assay for Non-Cytomegalovirus Infection in Lung Transplant Recipients: A Multicenter Prospective Observational Study.

Introduction: Immune cell functional assay (ImmuKnow®) is a non-invasive method that measures the state of cellular immunity in immunosuppressed patients. We studied the prognostic value of the assay for predicting non-cytomegalovirus (CMV) infections in lung transplant recipients.

Methods: A multicenter prospective observational study of 92 patients followed up from 6 to 12 months after transplantation was performed.

Intake of Vitamin D in Patients with Multiple Sclerosis in the Valencian Region and Its Possible Relationship with the Pathogenesis of the Disease.

(1) Background: Multiple sclerosis (MS) is a neurodegenerative disease characterized by pronounced inflammation. Interleukin 6 (IL-6) is an accurate marker for the state of inflammation, due to the high levels of this cytokine linked to the pathogenesis of the disease. These IL-6 levels could be lowered with an adequate dietary intake of vitamin D.

Predictive Value of Immune Cell Functional Assay for Non-Cytomegalovirus Infection in Lung Transplant Recipients: A Multicenter Prospective Observational Study.

Introduction: Immune cell functional assay (ImmuKnow®) is a non-invasive method that measures the state of cellular immunity in immunosuppressed patients. We studied the prognostic value of the assay for predicting non-cytomegalovirus (CMV) infections in lung transplant recipients.

Methods: A multicenter prospective observational study of 92 patients followed up from 6 to 12 months after transplantation was performed.

MUC4 is overexpressed in idiopathic pulmonary fibrosis and collaborates with transforming growth factor β inducing fibrotic responses.

Several mucins are implicated in idiopathic pulmonary fibrosis (IPF); however, there is no evidence regarding the role of MUC4 in the development of IPF. Here we demonstrated that MUC4 was overexpressed in IPF patients (n = 22) compared with healthy subjects (n = 21) and located in pulmonary arteries, bronchial epithelial cells, fibroblasts, and hyperplastic alveolar type II cells. Decreased expression of MUC4 using siRNA-MUC4 inhibited the mesenchymal/myofibroblast transformations of alveolar type II A549 cells and lung fibroblasts, as well as cell senescence and fibroblast proliferation induced by TGF-β1.

MUC1 intracellular bioactivation mediates lung fibrosis.

Background: Serum KL6/mucin 1 (MUC1) has been identified as a potential biomarker in idiopathic pulmonary fibrosis (IPF), but the role of MUC1 intracellular bioactivation in IPF is unknown.

Objective: To characterise MUC1 intracellular bioactivation in IPF.

Methods And Results: The expression and phosphorylation of Thr and Tyr on the intracellular MUC1-cytoplasmic tail (CT) was increased in patients with IPF (n=22) compared with healthy subjects (n=21) and localised to fibroblasts and hyperplastic alveolar type II cells.

JAK2 mediates lung fibrosis, pulmonary vascular remodelling and hypertension in idiopathic pulmonary fibrosis: an experimental study.

Background: Pulmonary hypertension (PH) is a common disorder in patients with idiopathic pulmonary fibrosis (IPF) and portends a poor prognosis. Recent studies using vasodilators approved for PH have failed in improving IPF mainly due to ventilation ()/perfusion () mismatching and oxygen desaturation. Janus kinase type 2 (JAK2) is a non-receptor tyrosine kinase activated by a broad spectrum of profibrotic and vasoactive mediators, but its role in PH associated to PH is unknown.

The JAK2 pathway is activated in idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal fibrotic disorder, with no curative therapies. The signal transducer and activator of transcription 3 (STAT3) protein is activated in lung fibroblasts and alveolar type II cells (ATII), thereby contributing to lung fibrosis in IPF. Although activation of Janus kinase 2 (JAK2) has been implicated in proliferative disorders, its role in IPF is unknown.

Patient-reported symptoms and functioning as indicators of mortality in advanced cystic fibrosis: A new tool for referral and selection for lung transplantation.

Background: Despite well-known risk factors and predictive survival models, many patients with cystic fibrosis (CF) die while on the waiting list for lung transplant. We evaluated whether specific Cystic Fibrosis Questionnaire (CFQ-R) scales provide additional benefit to conventional tools in identifying referral timing and waitlist mortality.

Methods: From January 2010 to January 2015, 152 patients (34% on the waitlist) were evaluated with the CFQ-R and standard protocol quarterly.

Vascular effects of sildenafil in patients with pulmonary fibrosis and pulmonary hypertension: an ex vivo/in vitro study.

Sildenafil improves the 6-min walking distance in patients with idiopathic pulmonary fibrosis (IPF) and right-sided ventricular systolic dysfunction.We analysed the previously unexplored role of sildenafil on vasoconstriction and remodelling of pulmonary arteries from patients with IPF and pulmonary hypertension (PH) ex vivo Pulmonary arteries from 18 donors without lung disease, nine IPF, eight PH+IPF and four PH patients were isolated to measure vasodilator and anti-contractile effects of sildenafil in isometric organ bath. Ventilation/perfusion was explored in an animal model of bleomycin lung fibrosis.

Impact of Single Nucleotide Polymorphisms (SNPs) on Immunosuppressive Therapy in Lung Transplantation.

Lung transplant patients present important variability in immunosuppressant blood concentrations during the first months after transplantation. Pharmacogenetics could explain part of this interindividual variability. We evaluated SNPs in genes that have previously shown correlations in other kinds of solid organ transplantation, namely ABCB1 and CYP3A5 genes with tacrolimus (Tac) and ABCC2, UGT1A9 and SLCO1B1 genes with mycophenolic acid (MPA), during the first six months after lung transplantation (51 patients).

[Balloon dilatation of the trachea as treatment for idiopathic tracheal stenosis].

The treatment of choice for idiopathic tracheal stenosis is tracheal resection and anastomosis, although some authors prefer more conservative management. Between January 1, 1996 and January 1, 2005, 8 patients-all women-with idiopathic tracheal stenosis were treated in the chest surgery department of the Hospital Universitario La Fe in Valencia, Spain. One case was treated by means of surgery and so was excluded from this study.

Donor fat embolism and primary graft dysfunction after lung transplantation.

Primary lung graft dysfunction is one of the major causes of perioperative morbidity and mortality in lung transplantation. Primary lung graft dysfunction is a clinical syndrome occurring in the immediate postoperative period after lung transplantation and is characterized by severe hypoxemia, pulmonary edema, and pulmonary infiltrates on chest x-ray film, requiring that the patient remain intubated and thus favoring pulmonary infection, sepsis, and subsequent multiple organ failure in the transplanted patient. It has recently been shown that unexpected pulmonary embolism is relatively common in the donor and is associated with primary lung graft dysfunction.

[Pneumonectomy in octogenarian patients].

Recent decades have witnessed a progressive aging of the population and a resulting increase in the numbers of elderly patients seeking health care. Since age and pneumonectomy are independent predictors of perioperative morbidity and mortality, such surgery is not recommended for octogenarian patients. We report the experience of 6 such patients who underwent pneumonectomy for squamous cell carcinoma in 5 cases and a typical carcinoid tumor in the sixth.

[Lung transplantation in cystic fibrosis: perioperative mortality].

Objective: To determine the incidence and causes of perioperative mortality following lung transplant for cystic fibrosis.

Patients And Methods: We analyzed the cases of 57 patients. Fifty-five patients received double lung transplants, 1 received a heart-double lung transplant, and 1 received a combined double lung and liver transplant.

[Use of blood products in patients treated surgically for stage I non-small cell lung cancer].

Objective: Retrospective study on the relation between the use of blood products and survival rates in patients treated surgically for stage I non-small cell lung cancer (NSCLC).

Patients And Methods: The study included 856 patients who underwent surgical resection from 1969 to 2000 for stage I NSCLC, classified histologically according to the current guidelines of the Spanish Society of Pulmonary and Thoracic Surgery (SEPAR). Patients who died in the postoperative period were excluded from the study.

[T2N1M0 non-small cell lung cancer: surgery and prognostic factors].

Objective: To determine the prognostic factors for the survival in a group of patients operated on for a non-small cell lung cancer classified as T2N1M0.

Patients And Methods: Two hundred sixteen patients treated exclusively with surgery were studied. Kaplan-Meier survival and Cox multivariable regression analyses were used.

[Non-small cell bronchogenic cancer in stage IA: mortality patterns after surgery].

Objective: To determine the causes of death in patients treated surgically for nonsmall cell lung cancer (NSCLC) in stage IA and to evaluate the impact on survival of not performing systematic lymph node dissection and of the number of nodes resected.

Patients And Methods: The study sample consisted of 156 patients operated on for NSCLC and classified in stage IA according to TNM staging. Only palpable or visible lymph nodes were dissected.

[Stage I nonsmall cell lung cancer up to 3 cm in diameter. Prognostic factors].

Objective: To assess the prognostic value of a series of clinicopathological variables in stage I nonsmall cell lung cancer, for tumors up to 3 cm in diameter.

Patients And Method: The study included 271 patients. Survival was analyzed with the Kaplan-Meier method.

[Preliminary results of indirect isotopic lymphography with colloidal rhenium marked with Tc 99m in urinary tract pathology].

The authors have carried out a study of a new method for studying the lymphatic system in patients with a neoplastic, urological pathology, by using lymphogammagraphy with radionuclids. It involves the comparative analysis of the lymphatic ganglion chains. This method consists in the subcutaneous injection into the interdigital space of a radionuclid, Colloidal, Rhenium Sulphide, marked with Tc-99m and with external detection by means of a gammacamera and with lymphatic channeling not being necessary.