Pulmonary thromboendarterectomy in chronic thromboembolic pulmonary hypertension: the Spanish experience

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) can be cured by pulmonary endarterectomy (PEA). It is considered the best and only curable treatment option for patients with accessible lesions evaluated as optimal candidates. We describe the experience of the two reference centers in Spain, in order to reinforce the need for referring CTEPH patients to a specialized center to be assessed by a Multidisciplinary Expert Team. Methods: We included a population of 338 patients who met the definition for CTEPH and underwent PEA between January 2007 and December 2019. The surgery was indicated in almost 60% of patients assessed. Demographic, anthropometric, hemodynamic and echocardiographic features are listed for PEA patients. Immediate and one-year postoperative outcomes as well as overall mortality were analyzed. Results: Mean age was 53.5±15.0 years, 53.8% were men; a total of 68.5% were in WHO functional class III-IV; and most of them were in a preoperative hemodynamic condition: mean pulmonary arterial pressure (mPAP) was 46.5±13.1 mmHg and mean pulmonary vascular resistance (PVR) was 764.5±392.8 dyn·s·cm-5. PEA surgery was performed with cardiopulmonary bypass (CBP) and circulatory arrest, with very few complications [including neurological, postoperative reperfusion edema, extracorporeal membrane oxygenation (ECMO) implant and cardiac failure] and optimal postoperative results, where exercise capacity increased and mPAP and PVR values decreased significantly. Presence of persistent pulmonary hypertension (PH) at the six-month right heart catheterization was evaluated. A 3.3% perioperative mortality was achieved. Overall, one-, three- and five-year survival rates were analyzed by Kaplan-Meier's method (94.8%, 93.3% and 90.5% respectively), as well as for residual PH patients. Mortality risk factors were assessed. Conclusions: Outstanding PEA results were seen in the immediate, one-year and long-term outcomes. The incidence of complications, including in-hospital mortality and long-term mortality were also below European rates

Impact of high-flow oxygen therapy during exercise in idiopathic pulmonary fibrosis: a pilot crossover clinical trial

[Background] Supplemental oxygen delivered with standard oxygen therapy (SOT) improves exercise capacity in patients with idiopathic pulmonary fibrosis (IPF). Although high-flow nasal cannula oxygen therapy (HFNC) improves oxygenation in other respiratory diseases, its impact on exercise performance has never been evaluated in IPF patients. We hypothesized that HFNC may improve exercise capacity in IPF subjects compared to SOT.[Methods] This was a prospective, crossover, pilot randomized trial that compared both oxygenation methods during a constant submaximal cardiopulmonary exercise test (CPET) in IPF patients with exertional oxygen saturation (SpO2) ≤ 85% in the 6-min walking test. The primary outcome was endurance time (Tlim). Secondary outcomes were muscle oxygen saturation (StO2) and respiratory and leg symptoms.[Results] Ten IPF patients [71.7 (6) years old, 90% males] were included. FVC and DLCO were 58 ± 11% and 31 ± 13% pred. respectively. Tlim during CPET was significantly greater using HFNC compared to SOT [494 ± 173 vs. 381 ± 137 s, p = 0.01]. HFNC also associated with a higher increase in inspiratory capacity (IC) [19.4 ± 14.2 vs. 7.1 ± 8.9%, respectively; p = 0.04], and a similar trend was observed in StO2 during exercise. No differences were found in respiratory or leg symptoms between the two oxygen devices.[Conclusions] This is the first study demonstrating that HFNC oxygen therapy improves exercise tolerance better than SOT in IPF patients with exertional desaturation. This might be explained by changes in ventilatory mechanics and muscle oxygenation. Further and larger studies are needed to confirm the benefits of HFNC in IPF patients and its potential usefulness in rehabilitation programs.This study has been funded by SEPAR 2017 (Fellowship) and Rio Hortega; ISCIII (Project and fellowship).Peer reviewe

Circulating Cell Biomarkers in Pulmonary Arterial Hypertension: Relationship with Clinical Heterogeneity and Therapeutic Response

Background: Endothelial dysfunction is central to PAH. In this study, we simultaneously analysed circulating levels of endothelial microvesicles (EMVs) and progenitor cells (PCs) in PAH and in controls, as biomarkers of pulmonary endothelial integrity and evaluated differences among PAH subtypes and as a response to treatment. Methods: Forty-seven controls and 144 patients with PAH (52 idiopathic, 9 heritable, 31 associated with systemic sclerosis, 15 associated with other connective tissue diseases, 20 associated with HIV and 17 associated with portal hypertension) were evaluated. Forty-four patients with scleroderma and 22 with HIV infection, but without PAH, were also studied. Circulating levels of EMVs, total (CD31+CD42b-) and activated (CD31+CD42b-CD62E+), as well as circulating PCs (CD34+CD133+CD45low) were measured by flow cytometry and the EMVs/PCs ratio was computed. In treatment-naïve patients, measurements were repeated after 3 months of PAH therapy. Results: Patients with PAH showed higher numbers of EMVs and a lower percentage of PCs, compared with healthy controls. The EMV/PC ratio was increased in PAH patients, and in patients with SSc or HIV without PAH. After starting PAH therapy, individual changes in EMVs and PCs were variable, without significant differences being observed as a group. Conclusion: PAH patients present disturbed vascular homeostasis, reflected in changes in circulating EMV and PC levels, which are not restored with PAH targeted therapy. Combined measurement of circulating EMVs and PCs could be foreseen as a potential biomarker of endothelial dysfunction in PAH

Implicaciones clínicas y biológicas del déficit de hierro en pacientes con enfermedad pulmonar obstructiva crónica : Efectos tras la reposición con hierro carboximaltosa

El déficit de hierro (DH) podría jugar un papel en la enfermedad pulmonar obstructiva crónica (EPOC) dado que es fundamental en la bioenergética celular. Estudio 1: Se analizaron 18 pacientes EPOC con DH y 18 pacientes EPOC sin DH evidenciándose en el grupo con DH mayor grado de sedentarismo y menor actividad física. Estudio 2: Ensayo clínico aleatorizado con hierro carboximaltosa vs placebo. El 52,3% de los pacientes tratados con hierro mejoraron la tolerancia al ejercicio frente al 18,2% en el grupo placebo. Estudio 3: Determinación de los niveles en suero de estrés oxidativo sistémico, antioxidantes y metabolismo del hierro. El ensayo clínico evidenció una disminución de los marcadores de estrés oxidativo tras la reposición con hierro. En definitiva, el DH en la EPOC se asoció con una mejoría de la capacidad de ejercicio y una disminución de los niveles de estrés oxidativo sistémico tras la reposición con hierro carboximaltosaIron deficiency (ID) may play a role in chronic obstructive pulmonary disease (COPD) as it is fundamental in cellular bioenergetics. Study 1: 18 COPD patients with ID and 18 COPD patients without ID were analysed, showing a more sedentarism and less physical activity in ID group. Study 2: Randomised clinical trial with iron carboxymaltose vs placebo. 52.3% of patients treated with iron improved exercise tolerance compared to 18.2% in the placebo group. Study 3: Determination of systemic oxidative stress levels, antioxidant markers and serum iron metabolism. This randomized clinical trial evidenced that iron replacement elicited a decline in serum oxidative stress markers. In conclusion, ID in COPD was associated with an improvement in exercise capacity and a decline in serum oxidative stress markers after replacement with iron carboxymaltose

Fragmento de cartílago, detectado en un ganglio linfático, tras punción aspirativa transbronquial guiada con ultrasonografía endobronquial

n the last years, the endoscopic units introduce the ultrasonic bronchofibrescope with a convex probe that allows for real-time needle aspiration of mediastinal and hilar lymph nodes guided by ultrasound images. This technique, known as real-time EBUS–TBNA, is minimally invasive and has the potential to replace mediastinoscopy, since it enables the same part of the mediastinum to be accessed

Iron Depletion in Systemic and Muscle Compartments Defines a Specific Phenotype of Severe COPD in Female and Male Patients: Implications in Exercise Tolerance

We hypothesized that iron content and regulatory factors, which may be involved in exercise tolerance, are differentially expressed in systemic and muscle compartments in iron deficient severe chronic obstructive pulmonary disease (COPD) patients. In the vastus lateralis and blood of severe COPD patients with/without iron depletion, iron content and regulators, exercise capacity, and muscle function were evaluated in 40 severe COPD patients: non-iron deficiency (NID) and iron deficiency (ID) (20 patients/group). In ID compared to NID patients, exercise capacity, muscle iron and ferritin content, serum transferrin saturation, hepcidin-25, and hemojuvelin decreased, while serum transferrin and soluble transferrin receptor and muscle IRP-1 and IRP-2 increased. Among all COPD, a significant positive correlation was detected between FEV1 and serum transferrin saturation. In ID patients, significant positive correlations were detected between serum ferritin, hepcidin, and muscle iron content and exercise tolerance and between muscle IRP-2 and serum ferritin and hepcidin levels. In ID severe COPD patients, iron content and its regulators are differentially expressed. A potential crosstalk between systemic and muscle compartments was observed in the ID patients. Lung function and exercise capacity were associated with several markers of iron metabolism regulation. Iron status should be included in the overall assessment of COPD patients given its implications in their exercise performance

Nitrosative and oxidative stress, reduced antioxidant capacity, and fiber type switch in iron-deficient copd patients: analysis of muscle and systemic compartments

We hypothesized that a rise in the levels of oxidative/nitrosative stress markers and a decline in antioxidants might take place in systemic and muscle compartments of chronic obstructive pulmonary disease (COPD) patients with non-anemic iron deficiency. In COPD patients with/without iron depletion (n = 20/group), markers of oxidative/nitrosative stress and antioxidants were determined in blood and vastus lateralis (biopsies, muscle fiber phenotype). Iron metabolism, exercise, and limb muscle strength were assessed in all patients. In iron-deficient COPD compared to non-iron deficient patients, oxidative (lipofuscin) and nitrosative stress levels were greater in muscle and blood compartments and proportions of fast-twitch fibers, whereas levels of mitochondrial superoxide dismutase (SOD) and Trolox equivalent antioxidant capacity (TEAC) decreased. In severe COPD, nitrosative stress and reduced antioxidant capacity were demonstrated in vastus lateralis and systemic compartments of iron-deficient patients. The slow- to fast-twitch muscle fiber switch towards a less resistant phenotype was significantly more prominent in muscles of these patients. Iron deficiency is associated with a specific pattern of nitrosative and oxidative stress and reduced antioxidant capacity in severe COPD irrespective of quadriceps muscle function. In clinical settings, parameters of iron metabolism and content should be routinely quantify given its implications in redox balance and exercise tolerance

Iron depletion in systemic and muscle compartments defines a specific phenotype of severe COPD in female and male patients: Implications in exercise tolerance

We hypothesized that iron content and regulatory factors, which may be involved in exercise tolerance, are differentially expressed in systemic and muscle compartments in iron deficient severe chronic obstructive pulmonary disease (COPD) patients. In the vastus lateralis and blood of severe COPD patients with/without iron depletion, iron content and regulators, exercise capacity, and muscle function were evaluated in 40 severe COPD patients: non-iron deficiency (NID) and iron deficiency (ID) (20 patients/group). In ID compared to NID patients, exercise capacity, muscle iron and ferritin content, serum transferrin saturation, hepcidin-25, and hemojuvelin decreased, while serum transferrin and soluble transferrin receptor and muscle IRP-1 and IRP-2 increased. Among all COPD, a significant positive correlation was detected between FEV1 and serum transferrin saturation. In ID patients, significant positive correlations were detected between serum ferritin, hepcidin, and muscle iron content and exercise tolerance and between muscle IRP-2 and serum ferritin and hepcidin levels. In ID severe COPD patients, iron content and its regulators are differentially expressed. A potential crosstalk between systemic and muscle compartments was observed in the ID patients. Lung function and exercise capacity were associated with several markers of iron metabolism regulation. Iron status should be included in the overall assessment of COPD patients given its implications in their exercise performance

Daptomycin versus glycopeptides for the treatment of Enterococcus faecium bacteraemia: a cohort study

Background: Ampicillin resistant and glycopeptide susceptible Enterococcus faecium bloodstream infection (GSEF-BSI) incidence has risen. However, the treatment of choice remains unknown. Daptomycin use for the treatment of enterococcal infections has increased, despite effectiveness and safety concerns. The objective was to compare the effectiveness and safety of daptomycin and glycopeptides in the treatment of GSEF-BSI. Methods: This was a single-centre, retrospective observational cohort study performed at Hospital del Mar (Barcelona, Spain), from January 2006-May 2018. The primary outcome was clinical cure at the end of the therapy, and secondary outcomes included 14-day, 30-day, in-hospital mortality, and length of stay. Results: From a total of 192 patients with GSEF-BSI, 54 (28.1%) were treated with glycopeptides and 17 (8.9%) with daptomycin. Patients treated with daptomycin presented a lower clinical cure than patients treated with glycopeptides (58.8% vs. 83.3%, RR 0.416 (95% CI 0.189-0.915)). After controlling for confounding variables by means of multivariate analysis the significative difference was confirmed (aOR 4.313, 95% CI, 1.053-17.660). The need for treatment discontinuation due to adverse events was similar. Conclusions: Patients with GSEF-BSI treated with glycopeptides showed a higher clinical cure than those treated with daptomycin