A novel experimental porcine model to assess the impact of differential pulmonary blood flow on ischemia–reperfusion injury after unilateral lung transplantation

Trasplantament de pulmó esquerre porcí; Disfunció primària de l’empelt; Resistència vascular pulmonarTrasplante de pulmón izquierdo porcino; Disfunción primaria del injerto; Resistencia vascular pulmonarPorcine left lung transplantation; Primary graft dysfunction; Pulmonary vascular resistanceBackground Primary graft dysfunction (PGD) remains a major obstacle after lung transplantation. Ischemia–reperfusion injury is a known contributor to the development of PGD following lung transplantation. We developed a novel approach to assess the impact of increased pulmonary blood flow in a large porcine single-left lung transplantation model. Materials Twelve porcine left lung transplants were divided in two groups (n = 6, in low- (LF) and high-flow (HF) group). Donor lungs were stored for 24 h on ice, followed by left lung transplantation. In the HF group, recipient animals were observed for 6 h after reperfusion with partially clamping right pulmonary artery to achieve a higher flow (target flow 40–60% of total cardiac output) to the transplanted lung compared to the LF group, where the right pulmonary artery was not clamped. Results Survival at 6 h was 100% in both groups. Histological, functional and biological assessment did not significantly differ between both groups during the first 6 h of reperfusion. injury was also present in the right native lung and showed signs compatible with the pathophysiological hallmarks of ischemia–reperfusion injury. Conclusions Partial clamping native pulmonary artery in large animal lung transplantation setting to study the impact of low versus high pulmonary flow on the development of ischemia reperfusion is feasible. In our study, differential blood flow had no effect on IRI. However, our findings might impact future studies with extracorporeal devices and represent a specific intra-operative problem during bilateral sequential single-lung transplantation.AN is supported by the KU Leuven (C24/18/073). AV is sponsored by a fundamental research Grant from the FWO (1102020 N). BMV is funded by the KU Leuven University (C24/15/030 and C16/19/005). SEV is sponsored by a grant from the Research Fund-Flanders (FWO 12G8715N). RV is a senior clinical research fellow of the FWO-Flanders. OCS solution was kindly offered by Transmedics (Andover, MA, USA) without any influence on our study. This research did not receive any other specific grants from funding agencies in the public, commercial, or not-for-profit sectors

Evaluación del dolor en el paciente oncológico en el servicio de Urgencias

Evaluación de las características de los pacientes oncológicos que acuden a Urgencias, concretamente analizando las características relacionadas con el dolor y su tratamiento. Se evalúa de esta manera potenciales causas que son barreras de adecuado control del dolor para este subgrupo de pacientes, estableciendo clara relación con el tratamiento analgésico de base

Evaluación de la expresión y correlación de HLA-G y sHLA-G como factores pronósticos en el carcinoma renal

El antígeno leucocitario humano G (HLA-G) presenta un amplio espectro de funciones inmunosupresoras, jugando un papel importante en la tolerancia materno-fetal y en la aceptación de los aloinjertos en los pacientes transplantados como consecuencia de sus propiedades tolerogénicas. Asimismo, se ha encontrado expresión de HLA-G tanto en tumores sólidos como en desórdenes linfoproliferativos, asociándose esta expresión a una disminución o pérdida de las respuestas inmunes mediadas por células NK y T, y a menudo a un aumento de la tumorogenicidad. En cuanto a sHLA-G, ha sido también detectado en el plasma de pacientes con diferentes tipos de enfermedades malignas. En cáncer renal, la expresión de HLA-G se ha detectado tanto en lesiones tumorales como en líneas celulares de cáncer renal, y se ha visto como los niveles plasmáticos de sHLA-G son mayores en los pacientes con CCR respecto a los controles sano

Evidence for shared genetic risk factors between lymphangioleiomyomatosis and pulmonary function

Lymphangioleiomyomatosis; Risk factors; Pulmonary functionLinfangioleiomiomatosis; Factores de riesgo; Función pulmonarLimfangioleiomiomatosi; Factors de risc; Funció pulmonarIntroduction Lymphangioleiomyomatosis (LAM) is a rare low-grade metastasising disease characterised by cystic lung destruction. The genetic basis of LAM remains incompletely determined, and the disease cell-of-origin is uncertain. We analysed the possibility of a shared genetic basis between LAM and cancer, and LAM and pulmonary function. Methods The results of genome-wide association studies of LAM, 17 cancer types and spirometry measures (forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC ratio and peak expiratory flow (PEF)) were analysed for genetic correlations, shared genetic variants and causality. Genomic and transcriptomic data were examined, and immunodetection assays were performed to evaluate pleiotropic genes. Results There were no significant overall genetic correlations between LAM and cancer, but LAM correlated negatively with FVC and PEF, and a trend in the same direction was observed for FEV1. 22 shared genetic variants were uncovered between LAM and pulmonary function, while seven shared variants were identified between LAM and cancer. The LAM-pulmonary function shared genetics identified four pleiotropic genes previously recognised in LAM single-cell transcriptomes: ADAM12, BNC2, NR2F2 and SP5. We had previously associated NR2F2 variants with LAM, and we identified its functional partner NR3C1 as another pleotropic factor. NR3C1 expression was confirmed in LAM lung lesions. Another candidate pleiotropic factor, CNTN2, was found more abundant in plasma of LAM patients than that of healthy women. Conclusions This study suggests the existence of a common genetic aetiology between LAM and pulmonary function

Conocimientos y prevalencia de consumo de tabaco de los estudiantes del Grado en Enfermería.

OBJETIVOS: Conocer la información sobre tabaquismo y la prevalencia de consumo de tabaco en la población de estudiantes del Grado de Enfermería de la Universidad de Zaragoza y de la Universidad San Jorge, además de evaluar las diferencias en la prevalencia según sexo, curso académico y centro universitario. METODOLOGÍA: Estudio descriptivo transversal. La población a estudio son los estudiantes de los cursos de primero y tercero del Grado en Enfermería de las Facultades de Ciencias de la Salud de UNIZAR y de USJ en el curso 2016-2017. El cuestionario elegido fue el utilizado en el estudio ECTEC. RESULTADOS: El 57,3% de los estudiantes no han fumado nunca, el 9,6% fuman ocasionalmente y el 22% fuman a diario. La edad media en la que fumaron por primera vez es de 15,5 años. No existen diferencias en la prevalencia según sexo y según el curso. La prevalencia de estudiantes de USJ que fuman a diario es más del doble (38,2%) que la de los estudiantes de UNIZAR (15,8%). CONCLUSIONES: La prevalencia de tabaquismo entre el alumnado de enfermería es similar a la de la población general, sin diferencias según sexo ni curso, pero con diferencias según la universidad. Se debe mejorar la formación que los estudiantes de enfermería reciben sobre tabaquismo en todos los aspectos, ya que estos profesionales son personal clave en la prevención y tratamiento del tabaquismo

Impact of interstitial lung disease on the survival of systemic sclerosis with pulmonary arterial hypertension

Respiratory tract diseases; Systemic sclerosisMalalties del tracte respiratori; Esclerosi sistèmicaEnfermedades del tracto respiratorio; Esclerosis sistémicaTo assess severity markers and outcomes of patients with systemic sclerosis (SSc) with or without pulmonary arterial hypertension (PAH-SSc/non-PAH-SSc), and the impact of interstitial lung disease (ILD) on PAH-SSc. Non-PAH-SSc patients from the Spanish SSc registry and PAH-SSc patients from the Spanish PAH registry were included. A total of 364 PAH-SSc and 1589 non-PAH-SSc patients were included. PAH-SSc patients had worse NYHA-functional class (NYHA-FC), worse forced vital capacity (FVC) (81.2 ± 20.6% vs 93.6 ± 20.6%, P < 0.001), worse tricuspid annular plane systolic excursion (TAPSE) (17.4 ± 5.2 mm vs 19.9 ± 6.7 mm, P < 0.001), higher incidence of pericardial effusion (30% vs 5.2%, P < 0.001) and similar prevalence of ILD (41.8% vs. 44.9%). In individuals with PAH-SSc, ILD was associated with worse hemodynamics and pulmonary function tests (PFT). Up-front combination therapy was used in 59.8% and 61.7% of patients with and without ILD, respectively. Five-year transplant-free survival rate was 41.1% in PAH-SSc patients and 93.9% in non-PAH-SSc patients (P < 0.001). Global survival of PAH-SSc patients was not affected by ILD regardless its severity. The multivariate survival analysis in PAH-SSc patients confirmed age at diagnosis, worse NYHA-FC, increased PVR, reduced DLCO, and lower management with up-front combination therapy as major risk factors. In conclusion, in PAH-SSc cohort risk of death was greatly increased by clinical, PFT, and hemodynamic factors, whereas it was decreased by up-front combination therapy. Concomitant ILD worsened hemodynamics and PFT in PAH-SSc but not survival regardless of FVC impairment

Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis

Biomarcador; Histamina; LimfangioleiomiomatosiBiomarcador; Histamina; LinfangioleiomiomatosisBiomarker; Histamine; LymphangioleiomyomatosisInhibition of mTOR is the standard of care for lymphangioleiomyomatosis (LAM). However, this therapy has variable tolerability and some patients show progressive decline of lung function despite treatment. LAM diagnosis and monitoring can also be challenging due to the heterogeneity of symptoms and insufficiency of non-invasive tests. Here, we propose monoamine-derived biomarkers that provide preclinical evidence for novel therapeutic approaches. The major histamine-derived metabolite methylimidazoleacetic acid (MIAA) is relatively more abundant in LAM plasma, and MIAA values are independent of VEGF-D. Higher levels of histamine are associated with poorer lung function and greater disease burden. Molecular and cellular analyses, and metabolic profiling confirmed active histamine signaling and metabolism. LAM tumorigenesis is reduced using approved drugs targeting monoamine oxidases A/B (clorgyline and rasagiline) or histamine H1 receptor (loratadine), and loratadine synergizes with rapamycin. Depletion of Maoa or Hrh1 expression, and administration of an L-histidine analog, or a low L-histidine diet, also reduce LAM tumorigenesis. These findings extend our knowledge of LAM biology and suggest possible ways of improving disease management.This research was supported by AELAM, The LAM Foundation (Seed Grant 2019), Instituto de Salud Carlos III grants PI15/00854, PI18/01029, and ICI19/00047 (co-funded by European Regional Development Fund (ERDF), a way to build Europe), Generalitat de Catalunya SGR grants 2014-364 and 2017-449, the CERCA Program, and ZonMW-TopZorg grant 842002003. C.L.M. acknowledges the financial support (PRA-2017-51 project) of the University of Pisa. A.U.K. is supported by Nottingham Trent University’s Independent Fellowship Scheme

Long-term results of sirolimus treatment in lymphangioleiomyomatosis: a single referral centre experience

Diagnòstic; Farmacoteràpia; Malalties del tracte respiratoriDiagnóstico; Farmacoterapia; Enfermedades del tracto respiratorioDiagnosis; Drug therapy; Respiratory tract diseasesThere are few published data on long-term treatment with sirolimus in lymphangioleiomyomatosis (LAM). The objective of this study was to describe the long-term effect of sirolimus in a series of LAM patients followed up in a referral centre, focusing on pulmonary function. We retrospectively reviewed a series of 48 patients with LAM diagnosed, followed up and treated with sirolimus in a single centre. Response to sirolimus was evaluated at 1 and 5 years. A negative sirolimus response was defined as an FEV1 decline greater than − 75 ml/year. A mixed-effects model was used to estimate the longitudinal changes in FEV1 (average slope), both as absolute (ml/year) and as predicted values (%predicted/year). From a total of 48 patients, 9 patients underwent lung transplantation and 4 died during the study. Mean (95% CI) FEV1 slope over 5 years was − 0.14 (− 26.13 to 25.85) ml/year in the whole LAM group, 42.55 (14.87 to 70.22) ml/year in the responder group, − 54.00 (− 71.60 to − 36.39) ml/year in the partial responder group and − 84.19 (− 113.5 to − 54.0) ml/year in the non-responder group. After 5 years of sirolimus treatment 59% had a positive response, 30% had a partial response and 11% had a negative response. Our study found that sirolimus treatment had a positive long-term effect on most LAM patients.E.R.L. received a pre-doctoral Grant from the Spanish Society of Pulmonology and Thoracic Surgery

Lymphangioleiomyomatosis: Searching for potential biomarkers

Biomarkers; Lymphangioleiomyomatosis; MetalloproteinasesBiomarcadores; Linfangioleiomiomatosis; MetaloproteinasasBiomarcadors; Limfangioleiomiomatosi; MetaloproteinasesBackground: Vascular endothelial growth factor-D (VEGF-D) is the most commonly used biomarker for diagnosing lymphangioleiomyomatosis (LAM). However, lung biopsy is often necessary as well; therefore, defining new biomarkers for LAM is crucial. The aim of this study was to describe the diagnostic accuracy of a variety of biomarkers. Methods: We assessed 13 analytes in serum related to extracellular matrix remodeling, lymphatic involvement and angiogenesis in a cohort of patients with LAM, comparing them with patients with other cystic lung diseases (OCLD) and healthy women. A scoring method based on the cut-point of each VEGF-D and metalloproteinase-2 (MMP-2) was used to evaluate the diagnostic performance of the marker combination. Results: A total of 97 subjects were recruited: 59 (61%) LAM patients, 18 (19%) OCLD patients, and 20 (20%) healthy female controls. MMP-2 was the only extracellular matrix remodeling biomarker able to differentiate LAM patients from OCLD and healthy patients. Serum MMP-2 was higher in LAM patients [median 578 (465–832) ng/ml] than in patients with OCLD and healthy controls [medians 360 (314–546) and 427 (365–513) ng/ml, respectively (p < 0.0001)]. The area under ROC curve (AUC) of MMP-2 was 0.785 and that of VEGF-D 0.815 (p = 0.6214). The sensitivity/specificity profiles of each biomarker (54/92% for MMP-2, 59/95% for VEGF-D) yielded a composite score (−6.36 + 0.0059 × VEGF-D + 0.0069 × MMP-2) with higher accuracy than each component alone (AUC 0.88 and sensitivity/specificity 79/87%). Conclusion: Combining MMP-2 and VEGF-D may increase diagnostic accuracy for LAM.This project was supported by the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), grant number: PI 638/2018. The funders have no role in study design, data and analysis collection, decision to publish, or preparation of the manuscript