Allergic bronchopulmonary aspergillosis

Allergic bronchopulmonary aspergillosis (ABPA) is caused by an exaggerated T(H)2 response to the ubiquitous mold Aspergillus fumigatus. ABPA develops in a small fraction of patients with cystic fibrosis and asthma, suggesting that intrinsic host defects play a major role in disease susceptibility. This article reviews current understanding of the immunopathology, clinical and laboratory findings, and diagnosis and management of ABPA. It highlights clinical and laboratory clues to differentiate ABPA from cystic fibrosis and asthma, which are challenging given clinical and serologic similarities. A practical diagnostic algorithm and management scheme to aid in the treatment of these patients is outlined.     

Clinical phenotypes of COPD: identification, definition and implications for guidelines

The term phenotype in the field of COPD is defined as "a single or combination of disease attributes that describe differences between individuals with COPD as they relate to clinically meaningful outcomes". Among all phenotypes described, there are three that are associated with prognosis and especially are associated with a different response to currently available therapies. There phenotypes are: the exacerbator, the overlap COPD-asthma and the emphysema-hyperinflation. The exacerbator is characterised by the presence of, at least, two exacerbations the previous year, and on top of long-acting bronchodilators, may require the use of antiinflammatory drugs. The overlap phenotype presents symptoms of increased variability of airflow and incompletely reversible airflow obstruction. Due to the underlying inflammatory profile, it uses to have a good therapeutic response to inhaled corticosteroids in addition to bronchodilators. Lastly, the emphysema phenotype presents a poor therapeutic response to the existing antiinflammatory drugs and long-acting bronchodilators together with rehabilitation are the treatments of choice. Identifying the peculiarities of the different phenotypes of COPD will allow us to implement a more personalised treatment, in which the characteristics of the patients, together with their severity will be key to choose the best treatment option.     

Documento de consenso sobre el fenotipo mixto EPOC-asma en la EPOC

Introduction

Although asthma and COPD are different pathologies, many patients share characteristics from both entities. These cases can have different evolutions and responses to treatment. Nevertheless, the evidence available is limited, and it is necessary to evaluate whether they represent a differential phenotype and provide recommendations about diagnosis and treatment, in addition to identifying possible gaps in our understanding of asthma and COPD.

Methods

A nation-wide consensus of experts in COPD in two stages: 1) during an initial meeting, the topics to be dealt with were established and a first draft of statements was elaborated with a structured «brainstorming» method; 2) consensus was reached with two rounds of e-mails, using a Likert-type scale.

Results

Consensus was reached about the existence of a differential clinical phenotype known as «Overlap Phenotype COPD-Asthma», whose diagnosis is made when 2 major criteria and 2 minor criteria are met. The major criteria include very positive bronchodilator test (increase in FEV₁ ≥ 15% and ≥ 400 ml), eosinophilia in sputum and personal history of asthma. Minor criteria include high total IgE, personal history of atopy and positive bronchodilator test (increase in FEV₁ ≥ 12% and ≥ 200 ml) on two or more occasions. The early use of individually-adjusted inhaled corticosteroids is recommended, and caution must be taken with their abrupt withdrawal. Meanwhile, in severe cases the use of triple therapy should be evaluated. Finally, there is an obvious lack of specific studies about the natural history and the treatment of these patients.

Conclusions

It is necessary to expand our knowledge about this phenotype in order to establish adequate guidelines and recommendations for its diagnosis and treatment.     

Increased afterload induces pathological cardiac hypertrophy: a new in vitro model

Increased afterload results in ‘pathological’ cardiac hypertrophy, the most important risk factor for the development of heart failure. Current in vitro models fall short in deciphering the mechanisms of hypertrophy induced by afterload enhancement. The aim of this study was to develop an experimental model that allows investigating the impact of afterload enhancement (AE) on work-performing heart muscles in vitro. Fibrin-based engineered heart tissue (EHT) was cast between two hollow elastic silicone posts in a 24-well cell culture format. After 2?weeks, the posts were reinforced with metal braces, which markedly increased afterload of the spontaneously beating EHTs. Serum-free, triiodothyronine-, and hydrocortisone-supplemented medium conditions were established to prevent undefined serum effects. Control EHTs were handled identically without reinforcement. Endothelin-1 (ET-1)- or phenylephrine (PE)-stimulated EHTs served as positive control for hypertrophy. Cardiomyocytes in EHTs enlarged by 28.4?% under AE and to a similar extent by ET-1- or PE-stimulation (40.6 or 23.6?%), as determined by dystrophin staining. Cardiomyocyte hypertrophy was accompanied by activation of the fetal gene program, increased glucose consumption, and increased mRNA levels and extracellular deposition of collagen-1. Importantly, afterload-enhanced EHTs exhibited reduced contractile force and impaired diastolic relaxation directly after release of the metal braces. These deleterious effects of afterload enhancement were preventable by endothelin-A, but not endothelin-B receptor blockade. Sustained afterload enhancement of EHTs alone is sufficient to induce pathological cardiac remodeling with reduced contractile function and increased glucose consumption. The model will be useful to investigate novel therapeutic approaches in a simple and fast manner.     

Younger donor's age and upfront tandem are two independent prognostic factors for survival in multiple myeloma patients treated by tandem autologous-allogeneic stem cell transplantation: a retrospective study from the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)

Background

How tandem autologous-allogeneic stem cell transplantation should be integrated in the treatment of multiple myeloma remains controversial. We examined the long-term outcome of patients with multiple myeloma managed with tandem autologous-allogeneic stem cell transplantation and present a prognostic factor analysis based on the experience of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC).

Design and Methods

This French, retrospective, registry-based study included 146 patients who had undergone tandem autologous-allogeneic transplantation for multiple myeloma at 20 SFGM-TC centers between 1998 and 2010. The patients included in the study had fully completed the two steps of a planned tandem autologous-allogeneic transplantation. No treatment had to be administered between the autologous and allogeneic parts of the tandem procedure.

Results

Seventy-seven patients (53%) underwent tandem autologous-allogeneic transplantation as part of upfront treatment, i.e. after a single line of treatment not including autologous transplantation. The median follow-up from the allogeneic transplant was 47.5 months (range, 1.2–132 months). At 4 years, the overall survival and event-free survival rates were 48% (95% CI 39–57 %) and 27% (95% CI 19–36), respectively. Eighteen patients (12%) experienced grade III–IV acute graft-versus-host disease and 43 patients (30%) had chronic graft-versus-host disease. The transplant-related mortality rate at 1 year was 15% (95% CI 10–22). Patients receiving tandem transplantation as upfront treatment had significantly improved event-free survival (36% versus 11%; P=0.005) and overall survival (56% versus 34%; P=0.02). Donor’s age ≤50 years was associated with improved event-free survival (35% versus 16%; P=0.005) and overall survival (54% versus 41%; P=0.02). In the multivariable analysis, upfront tandem transplantation, donor’s age ≤50 years and full chimerism were independent prognostic factors for better outcome.

Conclusions

We confirmed the feasibility of tandem autologour-allogeneic transplantation in heavily treated patients with multiple myeloma. We identified younger donor’s age and upfront tandem transplantation as two independent prognostic factors for survival which could be further explored in prospective studies.     

Coronary Stent Infections: A Case Report and Literature Review

Although rare, coronary artery stent infections are associated with a high mortality rate. Since the introduction of coronary stents in 1987, only 16 cases of infection have been reported. We report a new case in a 66-year-old woman who had undergone a difficult percutaneous coronary intervention procedure, during which 3 overlapping stents were implanted in the mid portion of the right coronary artery. Twenty-two days after the procedure, the patient died. Autopsy revealed the cause of death to be pericardial tamponade due to rupture of the right ventricular myocardium. The stented portion of the right coronary artery was enveloped by an abscess, and purulent material completely occluded the stents. Cultures of the myocardium were positive for methicillin-resistant Staphylococcus aureus. We conducted a review of the literature on coronary artery stent infections. Data suggest that early-onset infections (<10 days after stent implantation) are potentially amenable to medical therapy alone, but late-onset infections (≥10 days after implantation) or major complications necessitate combined surgical and medical therapy. Medical therapy consists of broad-spectrum antibiotics. Surgical intervention includes stent removal if possible, and abscess drainage or perforation repair when indicated.Key words: Blood vessel prosthesis implantation/adverse effects, coronary stent infections, prosthesis-related infections/complications/diagnosis/therapy, stents/adverse effects, Staphylococcus aureusCoronary artery stents have been in use for more than 2 decades. Stent infections are rare, hard to treat, and potentially devastating. Our treatment of a patient with a coronary stent abscess prompted us to review the literature. From our experience and the evaluation of previously reported cases,^1–14 we propose an approach for diagnosing and treating these infections.     

Metastatic colon cancer involving the right atrium

Colorectal cancer rarely metastasizes to the heart. In the world medical literature, we identified only 7 cases of well-documented colorectal cancer metastasis to the right atrium. Herein, we describe the case of a 72-year-old man in whom metastatic mucinous adenocarcinoma of the colon involved the right atrium and caused superior vena cava syndrome. To our knowledge, this is the first case report of sudden cardiac death due to embolization of metastatic colon cancer from the right atrium. We also present the first comprehensive case series review of this rare entity.Given improvements in diagnostic and therapeutic methods that have increased the longevity of many cancer patients, the detection of cardiac metastases is likely to increase in frequency. Accordingly, we recommend that previously asymptomatic cancer patients with a history of colorectal cancer who develop cardiac symptoms undergo prompt investigation for possible cardiac metastasis.