Patient-reported outcomes measures (PROMs) and patient-reported experience measures (PREMs) of COVID-19 telerehabilitation: Prospective pilot program.

Telemedicine is proving to be a useful tool in the telemonitoring of respiratory patients and telerehabilitation programs. The use of telemedicine has been proposed by the main medical societies because of the limited resources and the healthcare workers infection risk in the Coronavirus Disease 2019 (COVID-19) pandemic. The aim of this pilot program is to evaluate the feasibility of COVID-19 telerehabilitation program from the hospital to the home with clinical, functional and patient satisfaction outcomes. Rehabilitation was initiated in the hospital by a physiotherapist and complemented by "Estoi" (a mobile application), which was continued at home with telemonitoring and messaging with the medical team. Patients' habitual use of smartphones was not queried for inclusion. Sixteen patients were consecutively enrolled, 47% women with a mean age of 63 years old. 50% of patients completed ≥15 rehabilitation sessions. In total, 88% of patients referred that the mobile application incentive them to do more physical therapy, and 63% would choose telerehabilitation instead of center-based rehabilitation for new rehabilitation programs. Patient satisfaction (0-10) for the mobile application was 8.4 and 8.9 for the telerehabilitation program. Beginning telerehabilitation in the hospital could increase the efficacy and efficiency of physical therapy, which is safe for patients and healthcare workers. Following at home, this telerehabilitation program seems to encourage and empower patients who have reported high satisfaction. Further randomized studies with larger numbers of patients and multicenter studies are required to evaluate these results.

Pharmacokinetics of micafungin in patients treated with extracorporeal membrane oxygenation: an observational prospective study. / Farmacocinética da micafungina em pacientes tratados com oxigenação por membrana extracorpórea: um estudo observacional prospectivo.

OBJECTIVE: To determine micafungin plasma levels and pharmacokinetic behavior in patients treated with extracorporeal membrane oxygenation. METHODS: The samples were taken through an access point before and after the membrane in two tertiary hospitals in Spain. The times for the calculation of pharmacokinetic curves were before the administration of the drug and 1, 3, 5, 8, 18 and 24 hours after the beginning of the infusion on days one and four. The area under the curve, drug clearance, volume of distribution and plasma half-life time with a noncompartmental pharmacokinetic data analysis were calculated. RESULTS: The pharmacokinetics of the values analyzed on the first and fourth day of treatment did not show any concentration difference between the samples taken before the membrane (Cin) and those taken after the membrane (Cout), and the pharmacokinetic behavior was similar with different organ failures. The area under the curve (AUC) before the membrane on day 1 was 62.1 (95%CI 52.8 - 73.4) and the AUC after the membrane on this day was 63.4 (95%CI 52.4 - 76.7), p = 0.625. The AUC before the membrane on day 4 was 102.4 (95%CI 84.7 - 142.8) and the AUC was 100.9 (95%CI 78.2 - 138.8), p = 0.843. CONCLUSION: The pharmacokinetic parameters of micafungin were not significantly altered.

Farmacocinética da micafungina em pacientes tratados com oxigenação por membrana extracorpórea: um estudo observacional prospectivo / Pharmacokinetics of micafungin in patients treated with extracorporeal membrane oxygenation: an observational prospective study

RESUMO Objetivo: Determinar os níveis plasmáticos e o comportamento farmacocinético da micafungina em pacientes tratados com oxigenação por membrana extracorpórea. Métodos: As amostras foram colhidas por meio de pontos de acesso antes e depois da membrana, em dois hospitais espanhóis de nível terciário. Os momentos para o cálculo das curvas farmacocinéticas foram antes da administração do fármaco, e 1, 3, 5, 8, 18 e 24 horas após o início da infusão nos dias 1 e 4 de tratamento. Calcularam-se a área sob a curva, a depuração do fármaco, o volume de distribuição e a meia-vida plasmática por meio de análise farmacocinética não compartimental. Resultados: Os valores farmacocinéticos analisados no primeiro e quarto dias de tratamento não mostram qualquer diferença de concentração entre amostras colhidas antes da membrana e após a membrana, e o comportamento farmacocinético foi similar na vigência de diferentes falências de órgãos. A área sob a curva antes da membrana no dia 1 foi de 62,1 (IC95% 52,8 - 73,4) e a área sob a curva após a membrana nesse mesmo dia foi de 63,4 (IC95% 52,4 - 76,7), com p = 0,625. A área sob a curva antes da membrana no dia 4 foi de 102,4 (IC95% 84,7 - 142,8), enquanto a área sob a curva após a membrana nesse mesmo dia foi de 100,9 (IC95% 78,2 - 138,8), com p = 0,843. Conclusão: Os parâmetros farmacocinéticos da micafungina não foram alterados significantemente.

ABSTRACT Objective: To determine micafungin plasma levels and pharmacokinetic behavior in patients treated with extracorporeal membrane oxygenation. Methods: The samples were taken through an access point before and after the membrane in two tertiary hospitals in Spain. The times for the calculation of pharmacokinetic curves were before the administration of the drug and 1, 3, 5, 8, 18 and 24 hours after the beginning of the infusion on days one and four. The area under the curve, drug clearance, volume of distribution and plasma half-life time with a noncompartmental pharmacokinetic data analysis were calculated. Results: The pharmacokinetics of the values analyzed on the first and fourth day of treatment did not show any concentration difference between the samples taken before the membrane (Cin) and those taken after the membrane (Cout), and the pharmacokinetic behavior was similar with different organ failures. The area under the curve (AUC) before the membrane on day 1 was 62.1 (95%CI 52.8 - 73.4) and the AUC after the membrane on this day was 63.4 (95%CI 52.4 - 76.7), p = 0.625. The AUC before the membrane on day 4 was 102.4 (95%CI 84.7 - 142.8) and the AUC was 100.9 (95%CI 78.2 - 138.8), p = 0.843. Conclusion: The pharmacokinetic parameters of micafungin were not significantly altered.

Extracorporeal carbon dioxide removal with continuous renal replacement therapy. Case description and literature review. / Depuración extracorpórea de dióxido de carbono con reemplazo renal continuo. Descripción de un caso y revisión de la literatura.

In recent years and due, in part, to technological advances, the use of extracorporeal carbon dioxide removal systems paired with the use of extracorporeal membrane oxygenation has resurfaced. However, studies are lacking that establish its indications and evidence to support its use. These systems efficiently eliminate carbon dioxide in patients with hypercapnic respiratory failure using small-bore cannula, usually double-lumen cannula with a small membrane lung surface area. Currently, we have several systems with different types of membranes and sizes. Pump-driven veno-venous systems generate fewer complications than do arteriovenous systems. Both require systemic anticoagulation. The "lung-kidney" support system, by combining a removal system with hemofiltration, simultaneously eliminates carbon dioxide and performs continuous extrarenal replacement. We describe our initial experience with a combined system for extracorporeal carbon dioxide removal-continuous extrarenal replacement in a lung transplant patients with hypercapnic respiratory failure, barotrauma and associated acute renal failure. The most important technical aspects, the effectiveness of the system for the elimination of carbon dioxide and a review of the literature are described.

Depuración extracorpórea de dióxido de carbono con reemplazo renal continuo. Descripción de un caso y revisión de la literatura / Extracorporeal carbon dioxide removal with continuous renal replacement therapy. Case description and literature review

RESUMEN En los últimos años, y debido en parte a los avances tecnológicos, ha resurgido el uso de los sistemas de depuración extracorpórea de dióxido de carbono de manera pareja al uso de la oxigenación con membrana extracorpórea. No obstante, faltan estudios para establecer sus indicaciones y el nivel de evidencia para su uso. Estos sistemas permiten eliminar el dióxido de carbono de manera eficaz en pacientes con insuficiencia respiratoria hipercápnica con catéteres de pequeño calibre, habitualmente de doble luz y con pequeña superficie de membrana depuradora. En la actualidad disponemos de varios tipos de sistemas, con distinta versatilidad y tamaño de membrana. Los sistemas veno-venosos con bomba producen menos complicaciones que los arterio-venosos. Ambos precisan anticoagulación sistémica. El soporte "pulmón-riñón" mediante la combinación de un sistema depurador con un hemofiltro permitiría al mismo tiempo eliminar dióxido de carbono y realizar depuración extrarrenal continua. Describimos nuestra experiencia inicial con un sistema combinado de depuración extracorpórea de dióxido de carbono-depuración extrarrenal continua en un paciente con trasplante de pulmón, insuficiencia respiratoria hipercápnica, barotrauma y fallo renal agudo asociado. Se describen los aspectos técnicos más importantes, la efectividad del sistema para la eliminación de dióxido de carbono y se realiza una revisión de la literatura.

ABSTRACT In recent years and due, in part, to technological advances, the use of extracorporeal carbon dioxide removal systems paired with the use of extracorporeal membrane oxygenation has resurfaced. However, studies are lacking that establish its indications and evidence to support its use. These systems efficiently eliminate carbon dioxide in patients with hypercapnic respiratory failure using small-bore cannula, usually double-lumen cannula with a small membrane lung surface area. Currently, we have several systems with different types of membranes and sizes. Pump-driven veno-venous systems generate fewer complications than do arteriovenous systems. Both require systemic anticoagulation. The "lung-kidney" support system, by combining a removal system with hemofiltration, simultaneously eliminates carbon dioxide and performs continuous extrarenal replacement. We describe our initial experience with a combined system for extracorporeal carbon dioxide removal-continuous extrarenal replacement in a lung transplant patients with hypercapnic respiratory failure, barotrauma and associated acute renal failure. The most important technical aspects, the effectiveness of the system for the elimination of carbon dioxide and a review of the literature are described.

Imbalance in the Expression of Genes Associated with Purinergic Signalling in the Lung and Systemic Arteries of COPD Patients.

Growing evidence indicates that purinergic signalling is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD) and in the vascular remodelling that occurs in other disorders; however, its role in initial vascular changes of COPD is not entirely known. We hypothesised that expression of genes regulating extracellular ATP and adenosine levels would be altered in the lung and systemic arteries of COPD patients. Quantitative real-time PCR was performed to analyse the relative expression of 17 genes associated with purinergic signalling and inflammation in lungs and intercostal arteries of never smokers (NS) (n = 16), non-obstructed smokers (NOS) (n = 17) and COPD patients (n = 21). Gene expression of ATP-degrading enzymes was decreased in both tissues of NOS and COPD patients compared to NS. NT5E expression (gene transcribing for an AMP hydrolyzing ectonucleotidase) was increased in both tissues in NOS compared to the other groups. P1 and P2 receptors did not show changes in expression. Expression of genes associated with inflammation (interleukin-13) was upregulated only in lung tissues of COPD. These findings suggest that the expression of different extracellular ATP-degrading enzymes is altered in smokers (NOS and COPD patients), promoting inflammation. However, the high NT5E expression found only in NOS could compensate this inflammatory environment.

Defining the role of neutrophil-to-lymphocyte ratio in COPD: a systematic literature review.

COPD is characterized by a pulmonary and systemic inflammatory process. Several authors have reported the elevation of multiple inflammatory markers in patients with COPD; however, their use in routine clinical practice has limitations. The neutrophil-to-lymphocyte ratio (NLR) is a useful and cost-effective inflammatory marker derived from routine complete blood count. We performed a systematic literature review using the PRISMA statement. Twenty-two articles were included, recruiting 7,601 COPD patients and 784 healthy controls. Compared with controls, COPD patients had significantly higher NLR values. We found a significant correlation between the NLR and clinical/functional parameters (FEV1, mMRC, and BODE index) in COPD patients. Elevation of the NLR is associated with the diagnosis of acute exacerbation of COPD (pooled data propose a cut-off value of 3.34 with a median sensitivity, specificity, and area under the curve of 80%, 86%, and 0.86, respectively). Additionally, increased NLR is also associated with the diagnosis of a bacterial infection in exacerbated patients, with a cut-off value of 7.30, although with a low sensitivity and specificity. The NLR is an independent predictor of in-hospital and late mortality after exacerbation. In conclusion, the NLR could be a useful marker in COPD patients; however, further studies are needed to better identify the clinical value of the NLR.

Síndrome de takotsubo secundario a traumatismo raquimedular / Takotsubo syndrome secondary to spinal cord injury

Resumen Antecedentes: El síndrome de takotsubo secundario a traumatismo raquimedular cervical es infrecuente y no se describen series de casos en la literatura. Pacientes y método: Se describe el caso clínico de una mujer de 82 años que ingresó en la Unidad de Cuidados Intensivos tras traumatismo raquimedular cervical y como consecuencia desarrolló miocardiopatía de takotsubo. Resultado: Desarrollo de una miocardiopatía de takotsubo tras un traumatismo raquimedular cervical. Conclusiones: En la actualidad el diagnóstico de miocardiopatía de takotsubo en Cuidados Intensivos está en aumento, en parte por el uso de la ecocardiografía trastorácica por parte de los Intensivistas; con ello se descartan otras causas posibles de la misma y no sólo la cardiológica o la descarga catecolaminérgica secundaria a una situación de estrés.

Abstract Background: Takotsubo syndrome secondary to spinal cord injury is rare, and there are no case series described in the literature. Patients and method: A clinical case is presented of an 82 year-old woman admitted to the Intensive Care Unit after a spinal cord injury, and as a results developed Takotsubo cardiomyopathy. Results: A Takotsubo cardiomyopathy developed after a spinal cord injury. Conclusions: The diagnosis of Takotsubo cardiomyopathy is currently increasing in Intensive Care Units. This is partly due to use of transthoracic echocardiography by intensive care specialists. Using this technique they can rule out other possible causes of this condition, and not just the cardiological ones, or the catecholamine release following a stressful event.

Is the purinergic pathway involved in the pathology of COPD? Decreased lung CD39 expression at initial stages of COPD.

BACKGROUND: Extracellular adenosine triphosphate (ATP) is up-regulated in the airways of patients with chronic obstructive pulmonary disease (COPD), resulting in increased inflammation, bronchoconstriction, and cough. Although extracellular ATP levels are tightly controlled by nucleoside triphosphate diphosphohydrolase-1 (NTPDase1; also known as CD39) in the lungs, the role of CD39 in the pathology of COPD is unknown. We hypothesized that alterations in the expression and activity of CD39 could be part of the mechanisms for initiating and perpetuating the disease. METHODS: We analyzed CD39 gene and protein expression as well as ATPase enzyme activity in lung tissue samples of patients with COPD (n = 17), non-obstructed smokers (NOS) (n = 16), and never smokers (NS) (n = 13). Morphometry studies were performed to analyze pulmonary vascular remodeling. RESULTS: There was significantly decreased CD39 gene expression in the lungs of the COPD group (1.17 [0.85-1.81]) compared with the NOS group (1.88 [1.35-4.41]) and NS group (3.32 [1.23-5.39]) (p = 0.037). This attenuation correlated with higher systemic inflammation and intimal thickening of muscular pulmonary arteries in the COPD group. Lung CD39 protein levels were also lower in the COPD group (0.34 [0.22-0.92]) compared with the NOS group (0.67 [0.32-1.06]) and NS group (0.95 [0.4-1.1) (p = 0.133). Immunohistochemistry showed that CD39 was downregulated in lung parenchyma, epithelial bronchial cells, and the endothelial cells of pulmonary muscular arteries in the COPD group. ATPase activity in human pulmonary structures was reduced in the lungs of patients with COPD. CONCLUSION: An attenuation of CD39 expression and activity is presented in lung tissue of stable COPD patients, which could lead to pulmonary ATP accumulation, favoring the development of pulmonary inflammation and emphysema. This may be a mechanism underlying the development of COPD.

Impact of acute exacerbations on platelet reactivity in chronic obstructive pulmonary disease patients.

Background: A higher risk of atherothrombotic cardiovascular events, which are platelet-driven processes, has been described during acute exacerbations of chronic obstructive pulmonary disease (AECOPD). However, the relevance of platelet reactivity during AECOPD and whether this is affected by antiplatelet agents are not fully elucidated to date. This study aimed to evaluate whether platelet reactivity is augmented during an exacerbation in COPD patients with and without antiplatelet therapy and its association with systemic inflammatory parameters. Materials and methods: Prospective, observational, ex vivo investigation was conducted in consecutive patients suffering an exacerbation of COPD. Platelet reactivity was assessed during AECOPD and at stable state. Platelet function assays included: 1) vasodilator-stimulated phosphoprotein assay expressed as P2Y12 reactivity index (PRI), 2) multiple electrode aggregometry and 3) optical aggregometry. Systemic inflammatory parameters such as leukocyte count, interleukin-6 and fibrinogen were also assessed. Results: Higher platelet reactivity was observed during AECOPD compared to stability measured by vasodilator-stimulated phosphoprotein (PRI: 75.2%±1.9% vs 68.8%±2.4%, p=0.001). This augmented platelet aggregability was also observed in the subset of patients on antiplatelet therapy (PRI: 72.8%±3.1% vs 61.7%±7.5%, p=0.071). Consistent findings were observed with all other platelet function tests. Patients with greater enhancement of inflammatory markers during AECOPD were more likely to present a higher increase in platelet reactivity. Conclusion: Platelet reactivity is increased during AECOPD, which may contribute to the augmented cardiovascular risk of these patients. Additionally, the increase in platelet reactivity might be associated with an increment in inflammatory markers during exacerbations.

Effectiveness of a Respiratory Day Hospital Program to Reduce Admissions for Exacerbation in Patients with Severe COPD: A Prospective, Multicenter Study.

The respiratory Day Hospital (DH) is a care facility currently operating at various healthcare institutions. It monitors patients with severe chronic obstructive pulmonary disease (COPD) presenting repeated exacerbations with at least two hospital admissions per year. The main aim of the study was to evaluate the effectiveness of the DH program for controlling admissions for COPD exacerbations in this cohort of patients, and to identify clinical factors associated with hospitalizations and mortality. An observational prospective multicenter study was carried out at three hospitals. The sample comprised 150 consecutive patients (median age 70 [65-76] years, FEV1 33 [26-43]%, 97% males), included at the DH program. Over a one-year period, variables assessing effectiveness and use of healthcare resources were recorded. Factors associated with hospitalizations and mortality were identified. Patients made a median of 4[2-5] emergency visits due to COPD exacerbations with a median of 1[0-2] hospitalization(s)/year. Most of exacerbations (77%) were evaluated at the DH, but there were fewer hospitalizations from the DH than from the emergency department (21% vs. 81%, p < 0.001). In all, 29% of the patients had at least two admissions; these were the patients with the most severe disease. Age, readmission at 30-days and the presence of respiratory failure were the predictors of mortality. In conclusion, the DH program is an effective model for reducing hospitalizations in this cohort of patients. In all, 29% of the patients required two hospital admissions or more; these patients had more advanced disease and poorer prognosis, and would be most likely to benefit from additional care support.

Vascular disease in COPD: Systemic and pulmonary expression of PARC (Pulmonary and Activation-Regulated Chemokine).

INTRODUCTION: The role of Pulmonary and Activation-Regulated Chemokine (PARC) in the physiopathology of Chronic Obstructive Pulmonary Disease (COPD) is not fully understood. The aim of the present study is to analyze the expression of PARC in lung tissue and its relationship with the vascular remodeling of the systemic and pulmonary arteries of COPD subjects. METHODS: To achieve this objective, protein and gene expression experiments, together with ELISA assays, were performed on the lung tissue, intercostal arteries and serum samples from COPD patients, non-obstructed smokers (NOS) and never-smokers (NS). RESULTS: A total of 57 subjects were included in the analysis (23 COPD, 18 NOS and 16 NS). In the comparisons between groups, a significantly increased lung protein expression of PARC was observed in the COPD group compared to the NOS group (1.96±0.22 vs. 1.29±0.27, P-adjusted = 0.038). PARC was located predominantly in the smooth muscle cells of the remodeled pulmonary muscular arteries and the macrophage-rich area of the alveolar parenchyma. No differences were detected in PARC gene expression analyses. The protein content of PARC in the intercostal arteries were similar between groups, though little remodeling was observed in these arteries. Circulating levels of PARC were numerically higher in patients with COPD compared to NOS and NS. CONCLUSION: The results of the present study suggest an increased lung protein expression of PARC in COPD subjects. This protein was mainly localized in the smooth muscle cells of the pulmonary muscular arteries and was associated with the severity of intimal thickening, indicating its possible role in this remodeling process.

Inflammatory markers and circulating extracellular matrix proteins in patients with chronic obstructive pulmonary disease and left ventricular diastolic dysfunction.

BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is a frequent condition in chronic obstructive pulmonary disease (COPD). Tenascin-C (Tn-C) and matrix metalloproteinase-9 (MMP-9) are extracellular matrix proteins associated with myocardial fibrosis and wall remodeling because of inflammation. OBJECTIVE: To determine whether the circulating levels of inflammatory markers, Tn-C and MMP-9 are associated with LVDD in COPD patients. METHODS: Forty-two severe stable COPD patients (64 ± 8 years, 88% male, FEV1% 38 ± 5.7) and a control group (n = 11) were included. Pulmonary function tests and a Doppler echocardiography were performed on COPD patients. Baseline serum levels of C-reactive protein (CRP), leukocytes, fibrinogen, interleukins (IL) 6 and 8, Tn-C and MMP-9 were analyzed in all participants. RESULTS: COPD patients were classified in two groups: LVDD (n = 35) and non-LVDD (n = 7). Serum levels of IL-6 and CRP were higher in the LVDD group compared to the non-LVDD group [median(IQR)] [3.46 pg/mL (2.36-4.74) vs 1.87 pg/mL (1.10-3.28), P = 0.045] and [6.0 mg/L (3.0-13.0) vs 1.0 mg/L (1.0-2.3), P = 0.001], respectively. The same trend was observed in the analysis adjusted by age and BMI, being significant for CRP (P = 0.04). Circulating IL-6 was associated with the type of LVDD, being higher in the type-II (P = 0.046). Obese patients with COPD-LVDD showed a higher level of inflammatory markers (P = 0.021). Tn-C were significantly higher in patients with LVDD type-II compared to type-I [1422 ng/mL (826-1948) vs 781 ng/mL (640-1139), P = 0.015], without differences in MMP-9. CONCLUSIONS: Severe COPD patients with LVDD showed a different inflammatory pattern, suggesting a link between low-grade inflammation and the presence of LVDD. In COPD, high levels of Tn-C are related to LVDD type-II.

Systemic and Pulmonary Vascular Remodelling in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is associated with subclinical systemic atherosclerosis and pulmonary vascular remodelling characterized by intimal hyperplasia and luminal narrowing. We aimed to determine differences in the intimal thickening of systemic and pulmonary arteries in COPD subjects and smokers. Secondary aims include comparisons with a non-smokers group; determining the clinical variables associated with systemic and pulmonary intimal thickening, and the correlations between systemic and pulmonary remodelling changes. METHODS: All consecutive subjects undergoing lung resection were included and divided into 3 groups: 1) COPD, 2) smokers, and 3) non-smokers. Sections of the 5th intercostal artery and muscular pulmonary arteries were measured by histo-morphometry. Four parameters of intimal thickening were evaluated: 1) percentage of intimal area (%IA), 2) percentage of luminal narrowing, 3) intimal thickness index, and 4) intima-to-media ratio. RESULTS: In the adjusted analysis, the systemic arteries of COPD subjects showed greater intimal thickening (%IA) than those of smokers (15.6±1.5% vs. 14.2±1.6%, p = 0.038). In the pulmonary arteries, significant differences were observed for %IA between the 2 groups (37.3±2.2% vs. 29.3±2.3%, p = 0.016). Among clinical factors, metabolic syndrome, gender and COPD status were associated with the systemic intimal thickening, while only COPD status was associated with pulmonary intimal thickening. A correlation between the %IA of the systemic and pulmonary arteries was observed (Spearman's rho = 0.46, p = 0.008). CONCLUSIONS: Greater intimal thickening in systemic and pulmonary arteries is observed in COPD patients than in smokers. There is a correlation between systemic and pulmonary vascular remodelling in the overall population.

Treatment of patients with COPD and recurrent exacerbations: the role of infection and inflammation.

Exacerbations of COPD represent an important medical and health care problem. Certain susceptible patients suffer recurrent exacerbations and as a consequence have a poorer prognosis. The effects of bronchial infection, either acute or chronic, and of the inflammation characteristic of the disease itself raise the question of the possible role of antibiotics and anti-inflammatory agents in modulating the course of the disease. However, clinical guidelines base their recommendations on clinical trials that usually exclude more severe patients and patients with more comorbidities, and thus often fail to reflect the reality of clinicians attending more severe patients. In order to discuss aspects of clinical practice of relevance to pulmonologists in the treatment and prevention of recurrent exacerbations in patients with severe COPD, a panel discussion was organized involving expert pulmonologists who devote most of their professional activity to day hospital care. This article summarizes the scientific evidence currently available and the debate generated in relation to the following aspects: bacterial and viral infections, chronic bronchial infection and its treatment with cyclic oral or inhaled antibiotics, inflammatory mechanisms and their treatment, and the role of computerized tomography as a diagnostic tool in patients with severe COPD and frequent exacerbations.

Trombosis recurrente de la arteria hepática en tres trasplantes hepáticos sobre el mismo paciente: informe de caso / Recurrent hepatic artery thrombosis in three instances of liver transplant in a single patient: Case report

Introduction: Orthotopic liver transplantation (OLT) is currently the treatment of choice for patients with end-stage liver disease. Vascular complications can trigger a failure of treatment, so it must be watched closely. Clinical, diagnostic evaluation and interventions: We report the case of a patient taken three times to liver transplantation due to recurrent hepatic artery thrombosis. The perfusion defect persisted after the third transplant, although the short-term course was favourable. Conclusion: Hepatic artery thrombosis varies in its clinical presentation, but it usually requires early and aggressive management.

Introducción: El trasplante ortotópico hepático (TOH) es actualmente el tratamiento de elección para pacientes con enfermedades hepáticas terminales. Las complicaciones vasculares pueden desencadenar un fracaso del tratamiento, por lo que deben ser vigiladas estrechamente. Hallazgos clínicos, evaluación diagnóstica e intervenciones: presentamos el caso de un paciente sometido en tres ocasiones a trasplante hepático por trombosis recurrente de la arteria hepática. Tras el tercer trasplante persiste el defecto de perfusión, pese a lo cual la evolución a corto plazo fue favorable. Conclusión: las presentaciones clínicas de la trombosis de la arteria hepática son variables, pero suelen requerir un manejo agresivo y precoz.

Gene and Protein Expression of Fibronectin and Tenascin-C in Lung Samples from COPD Patients.

PURPOSE: Fibronectin (Fn) and tenascin-C (TnC) are two extracellular matrix proteins associated with remodeling changes. Fn and TnC gene and protein expression in lung tissue, including their predominant location in bronchial and pulmonary artery structures, have not yet been fully evaluated. The aim of the present study was to assess: (1) gene expression of Fn and TnC in lung samples from chronic obstructive pulmonary disease (COPD) and non-COPD subjects; and (2) protein content and location of Fn and TnC in both groups. METHODS: Consecutive subjects requiring lung resection due to lung cancer surgery were included. Lung specimens were examined for gene expression by quantitative real-time PCR (values expressed as fold change ratio). The analysis of their protein content and location was performed by western blot and immunohistochemical studies, respectively. Patients were divided into two cohorts according to COPD status. RESULTS: A total of 41 patients (20 with COPD and 21 without COPD) were included. An enhanced Fn gene expression was observed in the COPD group compared to the non-COPD group (4.73 ± 0.54 vs. 2.65 ± 0.57; P = 0.012), whereas no differences in gene TnC expression were observed (2.91 ± 0.44 vs. 2.60 ± 0.48; P = 0.633). No differences in lung protein content and location were found between groups. Immunohistochemical evaluation showed a predominantly vascular and bronchial location of Fn and TnC in both groups. CONCLUSIONS: An enhanced lung gene expression of Fn was observed in COPD subjects compared to non-COPD subjects. No differences were found in Fn protein expression or in TnC gene or protein expression among groups.

Roflumilast added to triple therapy in patients with severe COPD: a real life study.

BACKGROUND: Roflumilast is used in severe chronic obstructive pulmonary disease (COPD) patients with frequent exacerbations. However, limited information is available on its impact in a "real-life" population that may be receiving triple therapy. OBJECTIVE: This study aimed to evaluate the effectiveness and safety of roflumilast in COPD patients already receiving triple therapy (long-acting ß-agonist/inhaled corticosteroids and long-acting muscarinic antagonist). METHODS: Prospective registry that included COPD patients who were prescribed roflumilast added to triple therapy. The yearly rate of all COPD exacerbations before and after roflumilast and side effects related to the drug were registered. RESULTS: Among 55 patients prescribed 500 mg of roflumilast. Only 50.9% (n = 28) completed 1 year of therapy (roflumilast group). A reduction of all exacerbations with roflumilast was observed (2.75 ± 0.29 vs. 3.57 ± 0.26; P = 0.022), with a particular benefit in patients with ≥4 exacerbations prior to initiating therapy (3.55 ± 0.51 vs. 5.00 ± 0.30; P = 0.034). Side effects (mainly gastrointestinal) and treatment discontinuation occurred in 69.1% and 49.1% of the overall population, respectively. CONCLUSIONS: Roflumilast, when added to triple therapy, reduces exacerbations in a "real-life" population of severe COPD patients with frequent exacerbations. However, side effects are more common and lead more frequently to discontinuation of therapy than has been reported in trials.