Local Anesthesia Thoracoscopy with versus without Midazolam: A Randomized Controlled Trial.

BACKGROUND: Medical thoracoscopy is the gold standard for the diagnosis of pleural diseases. To date, no consensus exists regarding the choice of sedative and analgesic agents in patients undergoing local anesthetic thoracoscopy (LAT), and questions are raised as to whether sedatives may add to respiratory side effects. OBJECTIVE: The aim of the study was to test the hypothesis that administration of midazolam associated with lidocaine versus lidocaine alone in patients with LAT adds to respiratory side effects. METHODS: We randomly assigned 80 patients to a 1:1 study to 2 groups: local anesthesia by lidocaine (n = 40) versus lidocaine and midazolam (n = 40), with the primary end point being the mean lowest oxygen saturation. The secondary end points were cardiovascular parameters, complications, days of drainage, hospital stay, and patients' quality of life (QoL) as assessed by a visual analog scale (VAS). RESULTS: The mean age of all patients was 66.6 ± 13.1 years. The study comprised 50 males (62.5%). No difference was observed in the demographics between the 2 groups. No significant difference was observed between the 2 groups in oxygen saturation (primary end point). A significant difference was observed in favor of the midazolam group regarding the QoL assessed by VAS. CONCLUSION: Midazolam does not add to respiratory side effects when it is used with lidocaine for LAT, while patients' QoL is actually improved in this group. Therefore, in our department, we changed our startegy in favor of the association of lidocaine and midazolam.

Clinical long-term outcome of non-specific pleuritis (NSP) after surgical or medical thoracoscopy.

BACKGROUND: Thoracoscopy, either "medical" or "surgical", is the gold standard to reveal the cause of pleural effusion by taking large biopsies. However, in some cases, the histology of pleural biopsies is inconclusive for a specific cause, describing a variable process of inflammation, encompassing for non-specific pleuritis (NSP). Questions are raised whether the surgical (or video-assisted thoracoscopic surgery, VATS) is doing better than the medical thoracoscopy (MT or pleuroscopy), but no direct comparison between the two techniques exist in the current bibliography. The aim of our retrospective study was to compare these two techniques to find whether there is any difference in the false negative cases of NSP. METHODS: We included in our study 295 patients with NSP, 179 patients who underwent VATS comparing to 116 patients who underwent MT for pleural effusion of initially undetermined cause, having a follow-up of at least one year. Analysis of patients' files, history, clinical examinations, further tests, and follow-up were recorded. RESULTS: The mean age of our patients was 58.5±19.1 and M/F gender was 216/79; no difference was observed between the two groups. The mean follow-up period was 47.3±20.7 months. After VATS, only one patient (0.55%) was finally diagnosed with pleural malignancy (false negative) while after MT 2 patients (1.7%). Negative predictive value for pleura-related malignancy for VATS was 0.994 and for MT 0.982. CONCLUSIONS: In patients with histological diagnosis of NSP both VATS and MT showed similar and excellent results of false negative cases and negative predictive value in excluding malignant pleural disease.

Dabigatran can cause eosinophilic pleural and pericardial effusion with blood eosinophilia.

Eosinophilic pleural effusions (EPE) account for 5%-8% of all exudative pleural effusions. A pleural effusion is defined as eosinophilic if it contains 10% or more eosinophils. We present the case of a 70-year-old man with EPE, blood eosinophilia and pericardial effusion due to dabigatran, a novel anti-thrombin agent.

Bilateral empyema treated by sequential pleuroscopy.

Bilateral empyema associated to infectious pericarditis is an extremely rare, yet life-threatening condition. Pleuroscopy-medical thoracoscopy has proved its efficacy in series of patients with empyema. Yet, all reported cases treated by this technique, concerned patients with pleural infection located to a single hemithorax. We present the case of a 71-year-old man with bilateral empyema treated successfully by sequential pleuroscopy, associated to infectious pericarditis.

Increased expression of epidermal growth factor receptor (EGF-R) in patients with different forms of lung fibrosis.

INTRODUCTION: Emerging evidence supports the role of epidermal growth factor-receptor (EGFR) in fibrogenesis. The aim of our study was to investigate the expression profiles of EGFR in three forms of IIPs, including idiopathic pulmonary fibrosis (IPF), cryptogenic organizing pneumonia (COP), and nonspecific interstitial pneumonia (NSIP). PATIENTS AND METHODS: Twenty newly diagnosed patients with IPF, 15 with COP, and 15 with NSIP (cellular, n = 4 and fibrotic, n = 11) were investigated. Fifteen paraffin blocks obtained from the normal part of lungs removed for benign lesions were used as controls. Immunohistochemistry was carried out using specific monoclonal antibody. Results were verified by qRT-PCR. RESULTS: A significant EGFR upregulation, both in protein and mRNA level, was observed in IPF, COP, and fibrotic NSIP samples compared to controls. EGFR was primarily localized in the hyperplastic alveolar epithelium surrounding areas of fibrosis in IPF, COP, and fibrotic NSIP samples, as assessed by double immunohistochemistry analysis with surfactant protein-A. EGFR mRNA levels were positively associated with indicators of lung fibrosis (type 1 collagen mRNA levels) and negatively correlated with functional prognostic parameters. CONCLUSIONS: We conclude that EGFR is upregulated in the hyperplastic alveolar epithelium in all three fibrotic forms of IIPs indicating a potential role during abnormal reepithelization.

Increased incidence of autoimmune markers in patients with combined pulmonary fibrosis and emphysema.

BACKGROUND: Combined pulmonary fibrosis and emphysema (CPFE) is an umbrella term encompassing upper lobe emphysema and lower lobe pulmonary fibrosis with pathogenesis elusive. The aim of our study was to investigate the incidence of autoimmune markers in patients with CPFE. METHODS: In this multicenter study we retrospectively evaluated records from patients with CPFE (n=40) and IPF (n=60) without emphysema. Baseline demographic characteristics, high-resolution computed tomography (HRCT), spirometry, histopathological, treatment, serum immunologic and survival data were investigated. B cell presence was estimated with CD20 immunostaining in representative lung biopsy samples from CPFE patients and control subjects. RESULTS: A statistically significant increased number of CPFE patients with elevated serum ANA with or without positive p-ANCA titers compared to patients with IPF without emphysema was observed. Patients with CPFE and positive autoimmune markers exhibited improved survival compared to patients with a negative autoimmune profile. A massive infiltration of clusters of CD20+ B cells forming lymphoid follicles within the fibrotic lung in CPFE patients with positive serum immunologic profile compared to patients with negative profile, was noted and positively correlated with improved survival. CONCLUSIONS: A significant proportion of patients with CPFE may present with underlying auto-immune disorders that may reside insidiously and be associated with favorable prognosis. Early identification of these patients using a panel of auto-antibodies may lead to more targeted and effective therapeutic applications.

Expression of hypoxia-inducible factor (HIF)-1a-vascular endothelial growth factor (VEGF)-inhibitory growth factor (ING)-4- axis in sarcoidosis patients.

BACKGROUND: Sarcoidosis is a granulomatous disorder of unknown etiology. The term of immunoangiostasis has been addressed by various studies as potentially involved in the disease pathogenesis. The aim of the study was to investigate the expression of the master regulator of angiogenesis hypoxia inducible factor (HIF)-1a - vascular endothelial growth factor (VEGF)- inhibitor of growth factor 4-(ING4) - axis within sarcoid granuloma. METHODS: A total of 37 patients with sarcoidosis stages II-III were recruited in our study. Tissue microarray technology coupled with immunohistochemistry analysis were applied to video-assisted thoracoscopic surgery (VATS) lung biopsy samples collected from 37 sarcoidosis patients and 24 controls underwent surgery for benign lesions of the lung. Computerized image analysis was used to quantify immunohistochemistry results. qRT-PCR was used to assess HIF-1a and ING4 expression in 10 sarcoidosis mediastinal lymph node and 10 control lung samples. RESULTS: HIF-1a and VEGF-ING4 expression, both in protein and mRNA level, was found to be downregulated and upregulated, respectively, in sarcoidosis samples compared to controls. Immunohistochemistry coupled with computerized image analysis revealed minimal expression of HIF-1a within sarcoid granulomas whereas an abundant staining of ING4 and VEGF in epithelioid cells was also visualized. CONCLUSIONS: Our data suggest an impairment of the HIF-1a - VEGF axis, potentialy arising by ING4 overexpression and ultimately resulting in angiostasis and monocyte recruitment within granulomas. The concept of immunoangiostasis as a possible protection mechanism against antigens of infectious origin needs further research to be verified.

Effect and safety of mycophenolate mofetil or sodium in systemic sclerosis-associated interstitial lung disease: a meta-analysis.

UNLABELLED: Background. Interstitial lung disease (ILD) is the most common complication of systemic sclerosis (SSc) with treatment ineffective. OBJECTIVE: The aim of this meta-analysis was to provide an estimate of the safety and efficacy profile of Mycophenolate Mofetil (MMF) or sodium (MMS) in SSc-ILD patients. Materials and Methods. All studies were reviewed systematically. The main end-points were safety and efficacy profile as estimated by forced vital capacity (FVC)% and diffusion capacity of the lung for carbon monoxide (DL(CO))% of the predicted normal value (%pred.) before and after treatment in patients with SSc-ILD. Quality assessment and data extraction were performed independently by two reviewers. Results. Seventeen studies were reviewed systematically. Six studies, one prospective, were eligible for analysis encompassing 69 patients, including 10 subjects from our, yet unpublished, retrospective study. There was no statistically significant difference in both efficacy outcomes of interest, including FVC% pred. (weighted mean difference 1.48, 95% confidence interval (CI): -2.77 to 5.72, P = 0.49) and DL(CO) % pred. (weighted mean difference -0.83, 95% CI: -4.75 to 3.09, P = 0.93). No cases of clinically significant side effects were documented. Conclusions. Meta-analysis data suggest that MMF is a safe therapeutic modality which was associated with functional stabilization in patients with SSc-ILD.