Jovan Matijasevic

Autofluorescence Imaging Videobronchoscopy Improves Assessment of Tumor Margins and Affects Therapeutic Strategy in Central Lung Cancer

OBJECTIVE Autofluorescence imaging (AFI) videobronchoscopy is a new endoscopic tool that improves visualization of neoplastic changes in the bronchial mucosa. The major aim of our study was to determine sensitivity and specificity of the technique in the assessment of tumor extent (margins). The secondary objective was to evaluate the possible effect of AFI on the change in therapeutic decisions of lung cancer treatment. METHODS In this prospective trial, we enrolled 104 patients in whom we performed 624 targeted biopsies, 3 from the pathologically altered mucosa (red-brownish or magenta colored) and 3 from randomly picked normal areas. We were using the Olympus BF-F260 videobronchoscope and EVIS LUCERA system. White light videobronchoscopy (WLB) preceded AFI examination and biopsy collection. All biopsy specimens were examined by a pathologist blinded to bronchoscopy findings, and where applicable surgically resected specimens were examined. RESULTS In 14.4% of the patients, AFI revealed a greater extent of the tumor than WLB, and in 11.5% that finding led to change in therapeutic decision (lesser or greater resection or avoidance of surgery). We found a significant correlation between tumor extent determined by AFI and changes in therapeutic decisions (P < 0.01). Sensitivity, specificity, positive predictive value and negative predictive value for AFI in the assessment of tumor extension were 93%, 92%, 92% and 93%, respectively. Corresponding results for WLB were 84%, 79%, 77% and 85%, respectively. Relative sensitivity of AFI is 1.11. CONCLUSIONS Our results confirm that AFI videobronchoscopy significantly improves the assessment of central lung cancer extension and influences the therapeutic strategy. This technique has greater sensitivity and specificity, in assessment of tumor margins, than WLB alone.

Interleukin-6 and procalcitonin as biomarkers in mortality prediction of hospitalized patients with community acquired pneumonia.

INTRODUCTION: Community acquired pneumonia (CAP) may present as life-threatening infection with uncertain progression and outcome of treatment. Primary aim of the trial was determination of the cut-off value of serum interleukin-6 (IL-6) and procalcitonin (PCT) above which, 30-day mortality in hospitalized patients with CAP, could be predicted with high sensitivity and specificity. We investigated correlation between serum levels of IL-6 and PCT at admission and available scoring systems of CAP (pneumonia severity index-PSI, modified early warning score-MEWS and (Confusion, Urea nitrogen, respiratory rate, Blood pressure, ≥65 years of age-CURB65). METHODS: This was prospective, non-randomized trial which included 101 patients with diagnosed CAP. PSI, MEWS and CURB65 were assessed on first day of hospitalization. IL-6 and PCT were also sampled on the first day of hospitalization. RESULTS: Based on ROC curve analysis (AUC ± SE = 0.934 ± 0.035; 95%CI(0.864-1.0); P = 0.000) hospitalized CAP patients with elevated IL-6 level have 93.4% higher risk level for lethal outcome. Cut-off value of 20.2 pg/ml IL-6 shows sensitivity of 84% and specificity of 87% in mortality prediction. ROC curve analysis confirmed significant role of procalcitonin as a mortality predictor in CAP patients (AUC ± SE = 0.667 ± 0.062; 95%CI(0.546-0.789); P = 0.012). Patients with elevated PCT level have 66.7% higher risk level for lethal outcome. As a predictor of mortality at the cut-off value of 2.56 ng/ml PCT shows sensitivity of 76% and specificity of 61.8%. CONCLUSIONS: Both IL-6 and PCI are significant for prediction of 30-day mortality in hospitalized patients with CAP. Serum levels of IL6 correlate with major CAP scoring systems.

Autofluorescence imaging videobronchoscopy in the detection of lung cancer: from research tool to everyday procedure

Autofluorescence imaging videobronchoscopy (AFI) is one of the new systems of autofluorescence bronchoscopy designed for thorough examination of bronchial mucosa. The integration of autofluorescence and videobronchoscopy provides clear images of normal and pathologically altered bronchial mucosa. Major indications for AFI include evaluation of early-stage lung cancer and detection of precancerous lesions. However, in recent years, the indications for AFI are widening, and this tool might find its place in routine daily bronchoscopic practice. With new indications for AFI, such as evaluation of tumor extension or follow-up after surgical resection, this tool might be more often used by bronchoscopists. A sharp learning curve and clear distinction between healthy and pathologically altered mucosa make this technology acceptable for young and inexperienced bronchoscopists. One of the major disadvantages of AFI is low specificity in the detection of premalignant lesions and early-stage lung cancer. This disadvantage could be overcome with the appearance of new and improved technologies in autofluorescence, such as the addition of backscattered light analysis, ultraviolet spectra, fluorescence-reflectance or dual digital systems. Quantitative image analysis is also one of the ways to improve objectivity and minimize observer errors. However, one of the most appropriate solutions would be the addition of AFI to narrow band imaging, and merging the two technologies into one videobronchoscope.

Patient-related independent clinical risk factors for early complications following Nd: YAG laser resection of lung cancer.

INTRODUCTION: Neodymium:yttrium aluminum garnet (Nd:YAG) laser resection is one of the most established interventional pulmonology techniques for immediate debulking of malignant central airway obstruction (CAO). The major aim of this study was to investigate the complication rate and identify clinical risk factors for complications in patients with advanced lung cancer. METHODS: In the period from January 2006 to January 2011, data sufficient for analysis were identified in 464 patients. Nd:YAG laser resection due to malignant CAO was performed in all patients. The procedure was carried out in general anesthesia. Complications after laser resection were defined as severe hypoxemia, global respiratory failure, arrhythmia requiring treatment, hemoptysis, pneumothorax, pneumomediastinum, pulmonary edema, tracheoesophageal fistulae, and death. Risk factors were defined as acute myocardial infarction within 6 months before treatment, hypertension, chronic arrhythmia, chronic obstructive pulmonary disease (COPD), stabilized cardiomyopathy, previous external beam radiotherapy, previous chemotherapy, and previous interventional pulmonology treatment. RESULTS: There was 76.1% male and 23.9% female patients in the study, 76.5% were current smokers, 17.2% former smokers, and 6.3% of nonsmokers. The majority of patients had squamous cell lung cancer (70%), small cell lung cancer was identified in 18.3%, adenocarcinoma in 3.4%, and metastases from lung primary in 8.2%. The overall complication rate was 8.4%. Statistically significant risk factors were age (P = 0.001), current smoking status (P = 0.012), arterial hypertension (P < 0.0001), chronic arrhythmia (P = 0.034), COPD (P < 0.0001), and stabilized cardiomyopathy (P < 0.0001). Independent clinical risk factors were age over 60 years (P = 0.026), arterial hypertension (P < 0.0001), and COPD (P < 0.0001). CONCLUSION: Closer monitoring of patients with identified risk factors is advisable prior and immediately after laser resection. In order to avoid or minimize complications, special attention should be directed toward patients who are current smokers, over 60 years of age, with arterial hypertension or COPD.

Detection of premalignant bronchial lesions can be significantly improved by combination of advanced bronchoscopic imaging techniques

BACKGROUND: The search for the most efficient bronchoscopic imaging tool in detection of early lung cancer is still active. The major aim of this study was to determine sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each bronchoscopic technique and their combination in detection of premalignant bronchial lesions. METHODS: This was a prospective trial that enrolled 96 patients with indication for bronchoscopy. Lesions were classified as visually positive if pathological fluorescence was observed under autofluorescence imaging (AFI) videobronchoscopy or dotted, tortuous, and abrupt-ending blood vessels were identified under narrow band imaging (NBI) videobronchoscopy. Squamous metaplasia, mild, moderate, or severe dysplasia, and carcinoma in situ (CIS) were regarded as histologically positive lesions. RESULTS: Sensitivity, specificity, PPV, and NPV of white light videobronchoscopy (WLB) in detection of premalignant lesions were 26.5%, 63.9%, 34.4%, and 54.9%, respectively; the corresponding values for AFI were 52%, 79.6%, 64.6%, and 69.9% respectively, for NBI were 66%, 84.6%, 75.4%, 77.7%, respectively, while the values for combination of NBI and AFI were 86.1%, 86.6%, 84.6%, and 88%, respectively. Combination of NBI and AFI significantly improves sensitivity when compared to each individual technique (P < 0.001). When specificity is of concern, combination of techniques improves specificity of WLB (P < 0.001) and specificity of AFI (P = 0.03), but it does not have significant influence on specificity of NBI (P = 0.53). CONCLUSION: Combination of NBI and AFI in detection of premalignant bronchial lesions increases both sensitivity and specificity of each technique. However, it seems that NBI is most sufficient and effective in detection of these lesions.

Diagnostic value of autofluorescence bronchoscopy in lung cancer

The role of autofluorescence bronchoscopy (AFB) was primarily investigated in regard to the detection of precancerous lesions of bronchial mucosa. Most of the results confirmed higher sensitivity for the detection of precancerous bronchial lesions, when compared to white light bronchoscopy (WLB) alone. However, it is commonly known that the specificity of AFB remains low. Our findings agree in terms of the detection of premalignant bronchial lesions and early lung cancer, but regarding the detection of synchronous lesions or in the evaluation of lung cancer extension, the specificity of AFB is significantly higher. There is still an ongoing debate in the scientific community whether or not autofluorescence should be used as a screening tool for lung cancer. Results of the majority of published series did not support the general use of AFB as a screening tool for lung cancer; however, these results suggest its use in groups of patients with a high risk of lung cancer. Despite this, some authors still do not recommend its use even in high‐risk cases. In recent years, the indications for AFB have been widening and this tool may find its place in routine bronchoscopy. With new indications for AFB, such as the evaluation of tumor extension or follow up after surgical resection, bronchoscopists may make use of this tool more often. A sharp learning curve and a clear distinction between healthy and pathologically altered mucosa make this technology acceptable for inexperienced bronchoscopists. We also investigate new hardware and software improvements in AFB. The addition of backscattered light analysis, ultraviolet spectra, fluorescence‐reflectance or dual digital systems could improve the diagnostic yield of this technology.

Candida bloodstream infections in Serbia: First multicentre report of a national prospective observational survey in intensive care units

Candida bloodstream infections (BSI) are a significant cause of mortality in intensive care units (ICU), hereof the prospective 12‐months (2014‐2015) hospital‐ and laboratory‐based survey was performed at the Serbian National Reference Medical Mycology Laboratory (NRMML). Candida identification was done by a matrix‐assisted laser desorption/ionisation time‐of‐flight mass spectrometry and a susceptibility test, according to the Clinical and Laboratory Standards Institute methodology. Among nine centres (265 beds; 10 820 patient admissions), four neonatal/paediatric (NICU/PICUs) and five adult centres (ICUs) participated, representing 89 beds and 3446 patient admissions, 166 beds and 7347 patient admissions respectively. The NRMML received 43 isolates, 17 from NICU/PICUs and 26 from adult ICUs. C. albicans dominated highly in NICU/PICUs (~71%), whereas C. albicans and C. parapsilosis were equally distributed within adults (46%, each), both accounting for ~90% of received isolates. The resistance to itraconazole and flucytosine were 25% and 2.4% respectively. In addition, the 2 C. albicans were azole cross‐resistant (4.6%). The overall incidence of CandidaBSI was ~3.97 cases/1000 patient admissions (4.93 in NICU/PICU and 3.53 in adult ICU). The 30‐day mortality was ~37%, most associated with C. tropicalis and C. glabrataBSI. Data from this national survey may contribute to improving the Balkan and Mediterranean region epidemiology of CandidaBSI within ICUs.

The effect of smoking on asthma prevalence and control

Introduction. Determinants of asthma and its clinical course include the interaction between various intrinsic and extrinsic factors, of which exposure to harmful tobacco particles is one of the most important preventable causes of increased morbidity and mortality related to asthma. However, it is surprising that the prevalence of cigarette smoking among patients with asthma is equivalent to prevalence among the general population. Smoking as a Risk Factor for Development of Asthma. Exposure to tobacco smoke stimulates the immune response that can co-occur with asthma, lead to the development of bronchial hyperactivity and chronic inflammation of the respiratory tract, thus favoring the onset of asthma during childhood, as well as adulthood. Asthma Control in Relation to Smoking Habits. Continuous exposure to noxious particles of tobacco smoke, dysfunction of small airways as well as an altered inflammatory response result in irreversible changes. The worsening symptoms and signs of illness can easily remain unnoticed since they develop gradually, so the patients are often unaware of the severity of illness. The Prevalence of Asthma Symptoms Among Smokers. Compared to non-smokers, smokers have more prevalent and severe symptoms at all stages of disease, which is usually related to body weight and overall duration of smoking. Cigarette Smoking as a Risk Factor for Asthma Exacerbation. Current and former smokers are almost twice as likely to have asthma exacerbations and frequent relapses over a short period of time which increases the risk of requiring intensive care treatment The Effect of Smoking on Lung Function. Reduced airway sensitivity to the application of standardized inhalation therapy and the need for additional medications to achieve disease control can lead to irreversible changes and the development of fixed bronchial obstruction.