Evaluation of rapid techniques for the detection of mycobacteria in sputum with scanty bacilli or clinically evident, smear negative cases of pulmonary and extra-pulmonary tuberculosis

The objective of the current study was to compare two rapid methods, the BBL Mycobacteria Growth Indicator Tube (MGIT TM) and Biotec FASTPlaque TB TM (FPTB) assays, with the conventional Löwenstein-Jensen (LJ) media assay to diagnose mycobacterial infections from paucibacillary clinical specimens. For evaluation of the clinical utility of the BBL MGIT TM and FPTB assays, respiratory tract specimens (n = 208), with scanty bacilli or clinically evident, smear negative cases and non-respiratory tract specimens (n = 119) were analyzed and the performance of each assay was compared with LJ media. MGIT and FPTB demonstrated a greater sensitivity (95.92% and 87.68%), specificity (94.59% and 98.78%), positive predictive value (94.91% and 99.16%) and negative predictive value (96.56% and 90.92%), respectively, compared to LJ culture for both respiratory tract and non-respiratory tract specimens. However, the FPTB assay was unable to detect nontuberculous mycobacteria and few Mycobacterium tuberculosis complex cases from paucibacillary clinical specimens. It is likely that the analytical sensitivity of FPTB is moderately low and may not be useful for the direct detection of tuberculosis in paucibacillary specimens. The current study concluded that MGIT was a dependable, highly efficient system for recovery of M. tuberculosis complexes and nontuberculous mycobacteria from both respiratory and non-respiratory tract specimens in combination with LJ media.

Dectin-1 and DC-SIGN polymorphisms associated with invasive pulmonary Aspergillosis infection.

The recognition of pathogen-derived structures by C-type lectins and the chemotactic activity mediated by the CCL2/CCR2 axis are critical steps in determining the host immune response to fungi. The present study was designed to investigate whether the presence of single nucleotide polymorphisms (SNPs) within DC-SIGN, Dectin-1, Dectin-2, CCL2 and CCR2 genes influence the risk of developing Invasive Pulmonary Aspergillosis (IPA). Twenty-seven SNPs were selected using a hybrid functional/tagging approach and genotyped in 182 haematological patients, fifty-seven of them diagnosed with proven or probable IPA according to the 2008 EORTC/MSG criteria. Association analysis revealed that carriers of the Dectin-1(rs3901533 T/T) and Dectin-1(rs7309123 G/G) genotypes and DC-SIGN(rs4804800 G), DC-SIGN(rs11465384 T), DC-SIGN(7248637 A) and DC-SIGN(7252229 C) alleles had a significantly increased risk of IPA infection (OR = 5.59 95%CI 1.37-22.77; OR = 4.91 95%CI 1.52-15.89; OR = 2.75 95%CI 1.27-5.95; OR = 2.70 95%CI 1.24-5.90; OR = 2.39 95%CI 1.09-5.22 and OR = 2.05 95%CI 1.00-4.22, respectively). There was also a significantly increased frequency of galactomannan positivity among patients carrying the Dectin-1(rs3901533_T) allele and Dectin-1(rs7309123_G/G) genotype. In addition, healthy individuals with this latter genotype showed a significantly decreased level of Dectin-1 mRNA expression compared to C-allele carriers, suggesting a role of the Dectin-1(rs7309123) polymorphism in determining the levels of Dectin-1 and, consequently, the level of susceptibility to IPA infection. SNP-SNP interaction (epistasis) analysis revealed significant interactions models including SNPs in Dectin-1, Dectin-2, CCL2 and CCR2 genes, with synergistic genetic effects. Although these results need to be further validated in larger cohorts, they suggest that Dectin-1, DC-SIGN, Dectin-2, CCL2 and CCR2 genetic variants influence the risk of IPA infection and might be useful in developing a risk-adapted prophylaxis.

Mise en place d'un cathéter veineux central chez l'adulte. 2. Technique détaillée [The central vein catheterization. 2. Procedure, step by step]

La pose d'un cathéter veineux central peut se faire par plusieurs abords. La connaissance de l'anatomie, du matériel, la maîtrise des détails de la procédure pour chaque type d'abord et une attention particulière à l'asepsie sont des prérequis importants pour limiter les risques de complications et pour donner une information complète et exhaustive au patient. Cet article peut être utilisé comme base pour le développement d'une check-list, utile pour les médecins qui doivent procéder à la pose d'un cathéter veineux central mais qui ne possèdent pas encore une maîtrise du geste. Several approaches exist for central vein catheterization. Mastery of the various steps of this procedure and understanding of the basics of asepsis are critical to prevent any complication. They also built the basis for an exhaustive communication with the patient, to obtain an informed consent. This article can in addition be used to develop a checklist in order to (self-)assess competence in procedural skills

Occult lung infarction may induce false interpretation of 18F-FDG PET in primary staging of pulmonary malignancies.

PURPOSE: The aim of the present report is to describe abnormal (18)F-fluorodeoxyglucose (FDG) accumulation patterns in the pleura and lung parenchyma in a group of lung cancer patients in whom lung infarction was present at the time of positron emission tomography (PET). METHODS: Between November 2002 and December 2003, a total of 145 patients (102 males, 43 females; age range 38-85 years) were subjected to whole-body FDG PET for initial staging (n=117) or restaging (n=11) of lung cancer or for evaluation of solitary pulmonary nodules (n=17). Of these patients, 24 displayed abnormal FDG accumulation in the lung parenchyma that was not consistent with the primary lesion under investigation (ipsilateral n=12, contralateral n=9 or bilateral n=3). Without correlative imaging, this additional FDG uptake would have been considered indeterminate in differential diagnosis. RESULTS: Of the 24 patients who were identified as having such lesions, six harboured secondary tumour nodules diagnosed as metastases, while in three the diagnosis of a synchronous second primary lung tumour was established. Additionally, nine patients were identified as having post-stenotic pneumonia and/or atelectasis (n=6) or granulomatous lung disease (n=3). In the remaining six (4% of all patients), a diagnosis of recent pulmonary embolism that topographically matched the additional FDG accumulation (SUV(max) range 1.4-8.6, mean 3.9) was made. Four of these six patients were known to have pulmonary embolism, and hence false positive interpretation was avoided by correlating the PET findings with those of the pre-existing diagnostic work-up. The remaining two patients were harbouring small occult infarctions that mimicked satellite nodules in the lung periphery. Based on histopathological results, the abnormal FDG accumulation in these two patients was attributed to the inflammatory reaction and tissue repair associated with the pathological cascade of pulmonary embolism. CONCLUSION: In patients with pulmonary malignancies, synchronous lung infarction may induce pathological FDG accumulation that can mimic active tumour manifestations. Identifying this potential pitfall may allow avoidance of false positive FDG PET interpretation.

Pulmonary biomarkers in COPD exacerbations: a systematic review.

Exacerbations of COPD (ECOPD) represent a major burden for patients and health care systems. Innovative sampling techniques have led to the identification of several pulmonary biomarkers. Although some molecules are promising, their usefulness in clinical practice is not yet established. Medline and Highwire databases were used to identify studies evaluating pulmonary sampled biomarkers in ECOPD. We combined 3 terms for ECOPD, 3 for biomarkers and 6 for the sampling method. Seventy-nine studies were considered eligible for inclusion in the review and were analyzed further. Pulmonary biomarkers sampled with non-invasive, semi-invasive and invasive methods were evaluated for their potential to illustrate the disease's clinical course, to correlate to clinical variables and to predict clinical outcomes, ECOPD etiology and response to treatment. According to published data several pulmonary biomarkers assessed in ECOPD have the potential to illustrate the natural history of disease through the modification of their levels. Among the clinically relevant molecules, those that have been studied the most and appear to be promising are spontaneous and induced sputum biomarkers for reflecting clinical severity and symptomatic recovery, as well as for directing towards an etiological diagnosis. Current evidence on the clinical usefulness of exhaled breath condensate and bronchoalveolar lavage biomarkers in ECOPD is limited. In conclusion, pulmonary biomarkers have the potential to provide information on the mechanisms underlying ECOPD, and several correlate with clinical variables and outcomes. However, on the basis of published evidence, no single molecule is adequately validated for wide clinical use. Clinical trials that incorporate biomarkers in decisional algorithms are required.

A multicenter study confirms CD226 gene association with systemic sclerosis-related pulmonary fibrosis.

INTRODUCTION CD226 genetic variants have been associated with a number of autoimmune diseases and recently with systemic sclerosis (SSc). The aim of this study was to test the influence of CD226 loci in SSc susceptibility, clinical phenotypes and autoantibody status in a large multicenter European population. METHODS A total of seven European populations of Caucasian ancestry were included, comprising 2,131 patients with SSc and 3,966 healthy controls. Three CD226 single nucleotide polymorphisms (SNPs), rs763361, rs3479968 and rs727088, were genotyped using Taqman 5'allelic discrimination assays. RESULTS Pooled analyses showed no evidence of association of the three SNPs, neither with the global disease nor with the analyzed subphenotypes. However, haplotype block analysis revealed a significant association for the TCG haplotype (SNP order: rs763361, rs34794968, rs727088) with lung fibrosis positive patients (PBonf = 3.18E-02 OR 1.27 (1.05 to 1.54)). CONCLUSION Our data suggest that the tested genetic variants do not individually influence SSc susceptibility but a CD226 three-variant haplotype is related with genetic predisposition to SSc-related pulmonary fibrosis.

Efficacy of two educational interventions about inhalation techniques in patients with chronic obstructive pulmonary disease (COPD). TECEPOC: study protocol for a partially randomized controlled trial (preference trial).

BACKGROUND Drugs for inhalation are the cornerstone of therapy in obstructive lung disease. We have observed that up to 75 % of patients do not perform a correct inhalation technique. The inability of patients to correctly use their inhaler device may be a direct consequence of insufficient or poor inhaler technique instruction. The objective of this study is to test the efficacy of two educational interventions to improve the inhalation techniques in patients with Chronic Obstructive Pulmonary Disease (COPD). METHODS This study uses both a multicenter patients´ preference trial and a comprehensive cohort design with 495 COPD-diagnosed patients selected by a non-probabilistic method of sampling from seven Primary Care Centers. The participants will be divided into two groups and five arms. The two groups are: 1) the patients´ preference group with two arms and 2) the randomized group with three arms. In the preference group, the two arms correspond to the two educational interventions (Intervention A and Intervention B) designed for this study. In the randomized group the three arms comprise: intervention A, intervention B and a control arm. Intervention A is written information (a leaflet describing the correct inhalation techniques). Intervention B is written information about inhalation techniques plus training by an instructor. Every patient in each group will be visited six times during the year of the study at health care center. DISCUSSION Our hypothesis is that the application of two educational interventions in patients with COPD who are treated with inhaled therapy will increase the number of patients who perform a correct inhalation technique by at least 25 %. We will evaluate the effectiveness of these interventions on patient inhalation technique improvement, considering that it will be adequate and feasible within the context of clinical practice.

Efficacy and safety of a multifactor intervention to improve therapeutic adherence in patients with chronic obstructive pulmonary disease (COPD): protocol for the ICEPOC study.

Low therapeutic adherence to medication is very common. Clinical effectiveness is related to dose rate and route of administration and so poor therapeutic adherence can reduce the clinical benefit of treatment. The therapeutic adherence of patients with chronic obstructive pulmonary disease (COPD) is extremely poor according to most studies. The research about COPD adherence has mainly focussed on quantifying its effect, and few studies have researched factors that affect non-adherence. Our study will evaluate the effectiveness of a multifactor intervention to improve the therapeutic adherence of COPD patients.

Nontuberculous mycobacteria in respiratory samples from patients with pulmonary tuberculosis in the state of Rondonia, Brazil

The main cause of pulmonary tuberculosis (TB) is infection with Mycobacterium tuberculosis (MTB). We aimed to evaluate the contribution of nontuberculous mycobacteria (NTM) to pulmonary disease in patients from the state of Rondônia using respiratory samples and epidemiological data from TB cases. Mycobacterium isolates were identified using a combination of conventional tests, polymerase chain reaction-based restriction enzyme analysis of hsp65 gene and hsp65 gene sequencing. Among the 1,812 cases suspected of having pulmonary TB, 444 yielded bacterial cultures, including 369 cases positive for MTB and 75 cases positive for NTM. Within the latter group, 14 species were identified as Mycobacterium abscessus, Mycobacterium avium, Mycobacterium fortuitum, Mycobacterium intracellulare, Mycobacterium gilvum, Mycobacterium gordonae, Mycobacterium asiaticum, Mycobacterium tusciae, Mycobacterium porcinum, Mycobacterium novocastrense, Mycobacterium simiae, Mycobacterium szulgai, Mycobacterium phlei and Mycobacterium holsaticum and 13 isolates could not be identified at the species level. The majority of NTM cases were observed in Porto Velho and the relative frequency of NTM compared with MTB was highest in Ji-Paraná. In approximately half of the TB subjects with NTM, a second sample containing NTM was obtained, confirming this as the disease-causing agent. The most frequently observed NTM species were M. abscessus and M. avium and because the former species is resistant to many antibiotics and displays unsatisfactory cure rates, the implementation of rapid identification of mycobacterium species is of considerable importance.

Hypertension artérielle pulmonaire primitive et maladie de Basedow [Primary pulmonary hypertension arterial and Basedow disease].

We report a case of a fifty year old woman with Graves' disease with positive AntiTPO antibodies and positive AntiTSH receptor antibodies, who was hospitalized with a right cardiac failure. A pulmonary hypertension was discovered on echocardiography. After adequate antithyroid therapy, the right cardiac failure regressed rapidly and pulmonary pressure normalised. An autoimmune process has often been proposed to explain the association between pulmonary hypertension and hyperthyroidism. We report the arguments supporting this autoimmune etiopathogenesis. We also discuss an other hypothesis based on a direct effect of thyroid hormones on the pulmonary circulation and the effects of high cardiac output associated with hyperthyroidism.

Prevalence and genetic characterisation of HTLV-1 and 2 dual infections in patients with pulmonary tuberculosis in Central-West Brazil

Human T-cell lymphotropic virus (HTLV) may impact the clinical course of tuberculosis (TB). Both infections are highly endemic in Brazil. The aim of this study was to assess the prevalence of HTLV-1/2 in TB patients in Central-West Brazil and to perform a genetic characterisation of the respective isolates. Of the 402 patients, six (1.49%) were positive for anti-HTLV and five (1.24%; 95% confidence interval: 0.46-3.05) were infected with HTLV-1/2. Genetic characterisation demonstrated that the four HTLV-1 isolates belonged to the Transcontinental subgroup A of the Cosmopolitan subtype a and that the HTLV-2 isolate belonged to subtype a (HTLV-2a/c). The prevalence of HTLV infection observed in this study is higher than that observed in local blood donors and the HTLV-1 and 2 subtypes identified are consistent with those circulating in Brazil.

Evaluation of four molecular methods for the diagnosis of tuberculosis in pulmonary and blood samples from immunocompromised patients

The present study analysed the concordance among four different molecular diagnostic methods for tuberculosis (TB) in pulmonary and blood samples from immunocompromised patients. A total of 165 blood and 194 sputum samples were collected from 181 human immunodeficiency virus (HIV)-infected patients with upper respiratory complaints, regardless of suspicious for TB. The samples were submitted for smear microscopy, culture and molecular tests: a laboratory-developed conventional polymerase chain reaction (PCR) and real-time quantitative PCR (qPCR) and the Gen-Probe and Detect-TB Ampligenix kits. The samples were handled blindly by all the technicians involved, from sample processing to results analysis. For sputum, the sensitivity and specificity were 100% and 96.7% for qPCR, 81.8% and 94.5% for Gen-Probe and 100% and 66.3% for Detect-TB, respectively. qPCR presented the best concordance with sputum culture [kappa (k) = 0.864)], followed by Gen-Probe (k = 0.682). For blood samples, qPCR showed 100% sensitivity and 92.3% specificity, with a substantial correlation with sputum culture (k = 0.754) and with the qPCR results obtained from sputum of the corresponding patient (k = 0.630). Conventional PCR demonstrated the worst results for sputa and blood, with a sensitivity of 100% vs. 88.9% and a specificity of 46.3% vs. 32%, respectively. Commercial or laboratory-developed molecular assays can overcome the difficulties in the diagnosis of TB in paucibacillary patients using conventional methods available in most laboratories.

Accidental cross-clamping of the superior vena cava: management and BIS evolution.

The case of a 38-year old man with recurrent adenocarcinoma of the right lung and infiltration of the thoracic wall, who underwent a right pneumonectomy with thoracic wall resection, is described. Dissection of the right pulmonary hilous was extremely difficult due to the previous operations. The superior vena cava (SVC) was accidentally ligated, resulting in profound hypotension and increased venous pressure in the internal jugular vein. Immediate blood aspiration through a 8.5-French introducer sheath lowered the venous congestion. After the SVC was cross-clamped, the Bispectral Index (BIS) acutely decreased to 0 and remained low during the resuscitation. Over the next 5 hours, BIS was directly affected by mean arterial pressure. Four days postoperatively, the patient was neurologically intact.

Multidetector CT Features of Mesenteric Vein Thrombosis.

Mesenteric vein thrombosis (MVT) accounts for 5%-15% of all mesenteric ischemic events and is classified as either primary or secondary. Primary MVT is idiopathic, whereas secondary MVT can result from a variety of underlying diseases and risk factors, including primary hypercoagulable states or prothrombotic disorders, myeloproliferative neoplasms, cancer (most frequently of the pancreas or liver), diverse inflammatory conditions, recent surgery, portal hypertension, and miscellaneous causes such as oral contraceptives or pregnancy. Clinical symptoms of MVT are rather nonspecific and are mainly characterized by abdominal pain. The mortality rate for MVT remains high, since even now the diagnosis is often delayed. Multidetector computed tomography (CT) is the modality of choice in this context. Although venous bowel ischemia occurs only infrequently with MVT, radiologists should be familiar with its multidetector CT features. Familiarity with the possible causes of MVT, the underlying pathogenic mechanisms associated with MVT, and the correlation between multidetector CT features and these pathogenic mechanisms is necessary to optimize medical management and improve patient care. © RSNA, 2012.