Stavros Anevlavis

A prospective study of the diagnostic utility of sputum Gram stain in pneumonia

INTRODUCTION Sputum Gram stain and culture have been said to be unreliable indicators of the microbiological diagnosis of bacterial pneumonia. The etiological diagnosis of pneumonia is surrounded by great degree of uncertainty. This uncertainty should be and can be calculated and incorporated in the diagnosis and treatment. STUDY OBJECTIVES To determine the diagnostic accuracy and diagnostic value of sputum Gram stain in etiological diagnosis and initial selection of antimicrobial therapy of bacterial community acquired pneumonia (CAP). DESIGN-METHOD: Prospective study of 1390 patients with CAP admitted January 2002-June 2008, to our institutions. Of the 1390 patients, 178 (12.8%) fulfilled the criteria for inclusion into this study (good-quality sputa and presence of the same microorganism in blood and sputum cultures which was used as gold standard for assessing the diagnostic accuracy and diagnostic value of sputum Gram stain). RESULTS The sensitivity of sputum Gram stain was 0.82 for Pneumococcal pneumonia, 0.76 for Staphylococcal pneumonia, 0.79 for Haemophilus influenzae pneumonia and 0.78 for Gram-negative bacilli pneumonia. The specificity of sputum Gram stain was 0.93 for Pneumococcal pneumonia, 0.96 for Staphylococcal pneumonia, 0.96 for H. influenzae pneumonia and 0.95 for Gram-negative bacilli pneumonia. The positive likelihood ratio (LR+) was 11.58 for Pneumococcal pneumonia, 19.38 for Staphylococcal pneumonia, 16.84 for H. influenzae pneumonia, 14.26 for Gram-negative bacilli pneumonia. The negative likelihood ratio (LR-) was 0.20 for Pneumococcal pneumonia, 0.25 for Staphylococcal pneumonia, 0.22 for H. influenzae pneumonia, and 0.23 for Gram-negative bacilli pneumonia. CONCLUSIONS Sputum Gram stain is a dependable diagnostic test for the early etiological diagnosis of bacterial CAP that helps in choosing orthological and appropriate initial antimicrobial therapy.

Serum biomarkers in interstitial lung diseases

The use of biomarkers in medicine lies in their ability to detect disease and support diagnostic and therapeutic decisions. New research and novel understanding of the molecular basis of the disease reveals an abundance of exciting new biomarkers who present a promise for use in the everyday clinical practice. The past fifteen years have seen the emergence of numerous clinical applications of several new molecules as biologic markers in the research field relevant to interstitial lung diseases (translational research). The scope of this review is to summarize the current state of knowledge about serum biomarkers in interstitial lung diseases and their potential value as prognostic and diagnostic tools and present some of the future perspectives and challenges.

Angiogenesis in Interstitial Lung Diseases: a pathogenetic hallmark or a bystander?

The past ten years parallels have been drawn between the biology of cancer and pulmonary fibrosis. The unremitting recruitment and maintenance of the altered fibroblast phenotype with generation and proliferation of immortal myofibroblasts is reminiscent with the transformation of cancer cells. A hallmark of tumorigenesis is the production of new blood vessels to facilitate tumor growth and mediate organ-specific metastases. On the other hand several chronic fibroproliferative disorders including fibrotic lung diseases are associated with aberrant angiogenesis. Angiogenesis, the process of new blood vessel formation is under strict regulation determined by a dual, yet opposing balance of angiogenic and angiostatic factors that promote or inhibit neovascularization, respectively. While numerous studies have examined so far the interplay between aberrant vascular and matrix remodeling the relative role of angiogenesis in the initiation and/or progression of the fibrotic cascade still remains elusive and controversial. The current article reviews data concerning the pathogenetic role of angiogenesis in the most prevalent and studied members of ILD disease-group such as IIPs and sarcoidosis, presents some of the future perspectives and formulates questions for potential further research.

The clinical significance of serum and bronchoalveolar lavage inflammatory cytokines in patients at risk for Acute Respiratory Distress Syndrome

BackgroundThe predictive role of many cytokines has not been well defined in Acute Respiratory Distress Syndrome (ARDS).MethodsWe measured prospectively IL-4, IL-6, IL-6 receptor, IL-8, and IL-10, in the serum and bronchoalveolar lavage fluid (BALF) in 59 patients who were admitted to ICU in order to identify predictive factors for the course and outcome of ARDS. The patients were divided into three groups: those fulfilling the criteria for ARDS (n = 20, group A), those at risk for ARDS and developed ARDS within 48 hours (n = 12, group B), and those at risk for ARDS but never developed ARDS (n = 27, group C).ResultsAn excellent negative predictive value for ARDS development was found for IL-6 in BALF and serum (100% and 95%, respectively). IL-8 in BALF and IL-8 and IL-10 serum levels were higher in non-survivors in all studied groups, and were associated with a high negative predictive value. A significant correlation was found between IL-8 and APACHE score (r = 0.60, p < 0.0001). Similarly, IL-6 and IL-6r were highly correlated with PaO2/FiO2 (r = -0.27, p < 0.05 and r = -0.55, p < 0.0001, respectively).ConclusionsBALF and serum levels of the studied cytokines on admission may provide valuable information for ARDS development in patients at risk, and outcome in patients either in ARDS or in at risk for ARDS.

Prognostic factors in patients presenting with pleural effusion revealing malignancy.

Background: The survival of patients with malignant pleural effusion is considered generally poor. Most of the studies reporting results of prognostic factors are retrospective, using pleural thoracentesis for diagnosis. The objectives of our study were to reveal possible prognostic factors in patients initially presenting with undiagnosed pleural effusion proven to be malignant by diagnostic thoracoscopy. Methods: Ninety consecutive patients, 48 of whom were male (53%), with a median age of 69 years (range 37-93) and a performance status (PS) of 0/1 (63%) and with initially undiagnosed pleural effusion that was proven to be malignant by thoracoscopy were evaluated. Survival time was defined as the time from thoracoscopic diagnosis to death or the last follow-up. A regression analysis was used to determine significant clinical and biological prognostic factors. Results: Lung carcinoma (44.4%), breast carcinoma (24.4%), and mesothelioma (12.2%) were the most frequent tumors diagnosed. The median overall survival was 11 months (range 0.5-55). The survival of the patients was related to the following factors: histology of the primary tumor (p = 0.008), PS (p < 0.001), white blood cells (p = 0.018), and the blood neutrophil-to-lymphocyte (N/L) ratio (p = 0.002). Multiple regression showed PS, histology, and the N/L ratio. Conclusion: The factors affecting survival in our patients were PS, primary tumor histology, and the N/L ratio. These factors may help physicians select patients for treatment and/or interventional procedures.

Community acquired bacterial pneumonia.

Importance of the field: Community-acquired pneumonia (CAP) is a common and potentially life-threatening illness that continues to be a major medical problem. Among infectious diseases, CAP is the leading cause of death in the world and is associated with a substantial economic burden to health are systems around the globe. Areas covered in this review: Recently identified clinical and biochemical tools promise to improve the assessment of CAP severity. Various prognostic scoring systems and predictive biomarkers have been proposed as tools to aid clinicians in key management decisions. This review provides a summary of current evidence about the use of prognostic scoring systems and biomarkers in the management of patients presenting with CAP. According to the existing guidelines, until more accurate and rapid diagnostic methods are available, the initial treatment for most patients with CAP will remain empirical. Some novel antibiotic and nonantibiotic therapies have recently been tested; some empirical antimicrobial regimens are still being debated. This review summarizes the recent advances in the field of therapy and novel approaches. We searched PubMed for English-language references published from 1997 to 2009 using combinations of the following terms: ‘community acquired pneumonia’, ‘community acquired bacterial pneumonia’, ‘therapy’, ‘antibiotics’, ‘antimicrobials’, ‘prognostic scoring systems’, ‘biomarkers’, ‘diagnostic testing’, ‘guidelines’ ‘etiological diagnosis’. What the reader will gain: A thorough description about recent advances in the field of therapy and novel approaches of CAP, as well as a summary of current evidence about the use of prognostic scoring systems and biomarkers in the management of patients presenting with CAP, is presented. Take home message: Recent developments have made significant contributions to the management of CAP patients. However, various hot topics remain open and urgently require prospective studies in order to optimize the outcomes of CAP.

Recombinant tissue plasminogen activator in the treatment of pleural infections in adults

BACKGROUND Intrapleural recombinant tissue plasminogen activator (r-TPA) has been successfully evaluated in pediatric patients with complicated parapneumonic pleural effusion (CPE) and pleural empyema (PE). Yet, there is no data concerning r-TPA in adults with CPE/PE. The aim of our study was to investigate the efficacy and complications of r-TPA in adult patients with CPE/PE. METHODS Twenty consecutive patients (mean age 50+/-18.9 years) with pleural infection (14 CPE and 6 PE) were included. Chest tube was inserted under guidance of chest ultrasound and/or computed tomography. After failure of pleural fluid drainage, 25mg of r-TPA was administered intrapleurally in a single daily dose. The evaluation was made according to imaging and clinical status. RESULTS The mean volume of fluid increased significantly after r-TPA administration (p<0.0001). White blood cells count (WBC) and C-reactive protein (CRP) were significantly improved after r-TPA instillations (both p<0.0001). Significant clinical and imaging improvement was noted in all but one patient after r-TPA administration (overall p<0.0001). Complications observed were mild: pain in 4 (25%) and local bleeding in 3 (15%) patients. The median number of r-TPA instillations was 3 (range 2-5). CONCLUSION Intrapleural instillation of r-TPA at a dose of 25 mg is a well-tolerated and effective treatment in 95% of our adult patients with CPE/PE.

Phase 1 trial of lipoplatin and gemcitabine as a second‐line chemotherapy in patients with nonsmall cell lung carcinoma

Lipoplatin is a new liposomal cisplatin that already has been tested in solid tumors, with encouraging results. The purpose of the current study was to determine the maximum tolerated dose (MTD) and the dose‐limiting toxicity (DLT) of a 21‒day regimen of lipoplatin plus a fixed dose of gemcitabine in patients with refractory or resistant nonsmall cell lung carcinoma (NSCLC) with an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.

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

BackgroundSarcoidosis 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.MethodsA 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.ResultsHIF-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.ConclusionsOur 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.

Plasma visfatin levels in severe obstructive sleep apnea—hypopnea syndrome

BackgroundObstructive sleep apnea syndrome (OSAS) is associated with obesity and insulin resistance. Visfatin is an insulin-mimicking adipokine, which is considered a link between obesity and insulin resistance. Aim of this study was to evaluate levels of plasma visfatin in patients with severe OSAS and examine their potential correlation with sleep characteristics and several biochemical parameters.MethodsNondiabetic patients with severe OSAS (Apnea Hypopnea Index > 30/h, n = 32) and healthy controls (Apnea Hypopnea Index < 5/h, n = 12), examined with polysomnography, underwent a biochemical analysis to estimate fasting levels of visfatin, glucose, insulin, C-peptide, and lipid profile.ResultsThe two groups were matched for age and body mass index (BMI). OSAS patients had significantly higher fasting insulin levels (p = 0.045), but no difference was shown in visfatin between patients and controls (p = 0.585). In OSAS patients, visfatin levels correlated positively with sleep latency (r = 0.539, p = 0.01) and triglyceride levels (r = 0.584, p = 0.036) and negatively with total sleep time, percentage of stage 2 and REM sleep, and LDL-cholesterol levels (r = −0.659 and p = 0.001; r = −0.496 and p = 0.019; r = −0.577 and p = 0.005; r = −0.804 and p = 0.003, respectively). No association was found, however, between visfatin levels and HOMA index or indices of nocturnal hypoxia.ConclusionsIn patients with severe OSAS, visfatin levels are associated with characteristics of sleep architecture. However, there is no correlation between visfatin and insulin resistance or nocturnal hypoxia.