Roberto del Pozo

Tratamiento médico y quirúrgico de la hipertensión pulmonar tromboembólica crónica: experiencia en un único centro

INTRODUCTION Pulmonary endarterectomy (PE) is the treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study was to analyze our experience in the medical and surgical management of CTEPH. METHODS We included 80 patients diagnosed with CTEPH between January 2000 and July 2012. Thirty two patients underwent PE and 48 received medical treatment (MT). We analyzed functional class (FC), six-minute walking distance (6MWD) and pulmonary hemodynamics. Mortality in both groups and periods were analyzed. RESULTS Patients who underwent PE were younger, mostly men, and had longer 6MWD. No differences were observed in pulmonary hemodynamics or FC at diagnosis. One year after treatment, all PE patients versus 41% in MT group were at FCI-II. At follow-up, the PE group showed greater increase in 6MWD, and greater reduction in mean pulmonary arterial pressure and pulmonary vascular resistance than the MT group (P<.05). Overall survival in the MT group at 1 and 5years was 83% and 69%, respectively. Conditional survival in patients alive 100days post-PE at 1 and 5years was 95% and 88%, respectively. Surgical mortality in operated patients in the first period (2000-2006) was 31,3%, and 6,3% in the second (2007-2012). CONCLUSIONS PE provides good clinical results, and improves pulmonary hemodynamics in patients who successfully overcome the immediate postoperative period. After a learning period, the current operatory mortality in our center is similar to international standards.

Effect of targeted therapy on circulating progenitor cells in precapillary pulmonary hypertension

BACKGROUND Endothelial dysfunction is key in the development of pulmonary hypertension (PH) and is associated with reduced number of circulating progenitor cells. Studies to date evaluating levels of circulating progenitor cells in PH have provided conflicting results. Current treatment of pulmonary arterial hypertension (PAH) and medical treatment of chronic thromboembolic pulmonary hypertension (CTEPH) targets endothelium dependent signalling pathways. The effect of PAH-targeted therapy on circulating progenitor cells has not been clearly established. OBJECTIVES To investigate whether levels of circulating progenitor cells in treatment-naïve patients with PAH or CTEPH differ from healthy subjects and to assess the effect of PAH-targeted therapy on the circulating levels of these progenitors. METHODS Thirty controls, 33 PAH and 11 CTEPH treatment-naïve patients were studied. Eighteen patients with PAH and 9 with CTEPH were re-evaluated 6-12months after starting PAH-targeted therapy. Levels of progenitors were measured by flow cytometry as CD45+CD34+ and CD45+CD34+CD133+ cells. RESULTS Compared with controls, the number of circulating progenitor cells was reduced in PAH but not in CTEPH. After 6-12months of treatment, levels of circulating progenitors increased in PAH and remained unchanged in CTEPH. Patients with lower exercise tolerance presented lower levels of circulating progenitors. No other relation was found between levels of progenitors and clinical or hemodynamic parameters. CONCLUSIONS Patients with PAH, but not those with CTEPH, present reduced levels of circulating progenitor cells. PAH-targeted therapy increases levels of progenitors in PAH but not in CTEPH, suggesting different involvement of progenitor cells in the pathobiology of these pulmonary hypertensive disorders.

Imbalance between endothelial damage and repair capacity in chronic obstructive pulmonary disease

Background Circulating endothelial microparticles (EMPs) and progenitor cells (PCs) are biological markers of endothelial function and endogenous repair capacity. The study was aimed to investigate whether COPD patients have an imbalance between EMPs to PCs compared to controls and to evaluate the effect of cigarette smoke on these circulating markers. Methods Circulating EMPs and PCs were determined by flow cytometry in 27 nonsmokers, 20 smokers and 61 COPD patients with moderate to severe airflow obstruction. We compared total EMPs (CD31+CD42b-), apoptotic if they co-expressed Annexin-V+ or activated if they co-expressed CD62E+, circulating PCs (CD34+CD133+CD45+) and the EMPs/PCs ratio between groups. Results COPD patients presented increased levels of total and apoptotic circulating EMPs, and an increased EMPs/PCs ratio, compared with nonsmokers. Women had less circulating PCs than men through all groups and those with COPD showed lower levels of PCs than both control groups. In smokers, circulating EMPs and PCs did not differ from nonsmokers, being the EMPs/PCs ratio in an intermediate position between COPD and nonsmokers. Conclusions We conclude that COPD patients present an imbalance between endothelial damage and repair capacity that might explain the frequent concurrence of cardiovascular disorders. Factors related to the disease itself and gender, rather than cigarette smoking, may account for this imbalance.

Real-life experience of inhaled iloprost for patients with pulmonary arterial hypertension: Insights from the Spanish REHAP registry

INTRODUCTION REHAP is a voluntary, observational Spanish registry of patients with pulmonary arterial hypertension. We analyzed the experience (use and effectiveness) with inhaled iloprost (inh-ILO) in real-life conditions during a 3-year period. METHODS Patients included were those with PAH ≥14 years recruited during 1998-2016 who had received inh-ILO. Variables were collected at the beginning of treatment (0 ± 3 months) and 12 ± 3/36 ± 6 months follow-up. Effectiveness was assessed in the intent-to-treat population as changes in functional class and/or physical performance and transplant-free survival from the beginning of treatment. Stopping inh-ILO-related survival was also assessed. Subanalyses included treatment strategy (first-line therapy -monotherapy or upfront combination- or sequential therapy) and risk of clinical worsening/death. RESULTS Inh-ILO was the most frequently used prostanoid in Spain, rendering 267 patients eligible for analysis. Median age was 54 years; 61% were WHO FC III. Sixty (23%) patients started inh-ILO as monotherapy, 27 (10%) as upfront combination and 180 (67%) sequentially. At 3-year follow-up significant clinical improvements were observed; however, transplant-free survival rate was 54%, being poorer in patients at high risk (63% vs. 85% in low risk patients; P < 0.001) and similar in the three treatment strategies. Only 25% patients remained on inh-ILO. Three-year after stopping inh-ILO-related survival rate was 24.7%. CONCLUSION Data from the REHAP collected during 3 years shows that inh-ILO has low effectiveness independently of the treatment strategy used, with a 3-year survival rate of 54% despite significant clinical improvements, probably due to the use in high-risk patients. Discontinuation rate was as high as 75%.

Neumonía atípica por Chlamydia psittaci. Cuatro casos relacionados

Hodgkin disease is derived from an alteration in the maturation and activation of B cells in the lymph nodes. It is characterized by the presence of lymphadenopathies. Approximately 25% of patients have general symptoms consisting of the so-called B symptoms: fever, night sweats, and weight loss. Diagnosis is obtained by biopsy, showing characteristic Reed–Sternberg cells on cytology. The nodular sclerosis variant is the most common and has the best prognosis. Treatment is based on chemotherapy and radiation therapy, depending on staging. The combination of sarcoidosis and lymphoma is unusual, and may be derived from a disordered immune system. Lymphomasarcoidosis syndrome was described by Brincker in 1986 after conducting 2 studies, the first in the Danish Clinical Epidemiology Institute, and another subsequent study. Brincker observed that the frequency of lymphoma in patients with pulmonary sarcoidosis was significantly higher than in the general population, the most common being Hodgkin disease, followed by non-Hodgkin lymphoma and other hematological cancers. He also concluded that sarcoidosis normally precedes the lymphoproliferative process by a short period of around 24 months; the inverse order is rarely seen.4 The development of sarcoidosis after receiving treatment for a lymphoproliferative process may be due to a hyperresponse of the immune system against the tumor cells.5 Patients with sarcoidosis may also experience an exacerbation after receiving anticancer treatment. Sarcoid reactions have been reported that are histologically identical to sarcoidosis, and these might be a marker of antitumor response mediated by macrophages activated by T cells.6 In conclusion, sarcoidosis and lymphoproliferative processes are diseases in which differential diagnosis can be complicated, but it is important to remember that both diseases may be found in the same patient, either consecutively or simultaneously.