Aleksandra Safianowska

Prognosis of acute respiratory distress syndrome in neutropenic cancer patients

To date, no study has been specifically designed to identify determinants of death in neutropenic cancer patients presenting with acute respiratory distress syndrome (ARDS). The aim of this study was to identify early predictive factors of 28-day mortality in these patients. Factors associated with 28-day mortality during intensive care unit (ICU) stay were also described. 70 consecutive cancer patients with ARDS and neutropenia were prospectively analysed over a 6-yr period. Mortality at 28 days was 63%. Factors independently associated with good prognosis were: lobar ARDS (OR 0.10, 95% CI 0.02–0.48), use of initial antibiotic treatment active on difficult to treat bacteria (ticarcillin-resistant Pseudomonas aeruginosa, Stenotrophomonas maltophilia or extended-spectrum &bgr;-lactamase-producing strains) (OR 0.08, 95% CI 0.02–0.33) and first-line chemotherapy (OR 0.08, 95% CI 0.02–0.37). During the ICU stay, mortality was associated with the markers of organ dysfunctions, the absence of neutropenia recovery and the use of vasopressors. During the first 3 weeks, the conditional probability of discharge alive from ICU did not decrease. At ICU admission, first-line chemotherapy, lobar ARDS and antibiotic treatment active on difficult-to-treat bacteria were associated with survival. During ICU stay, mortality was associated with organ dysfunctions and use of vasopressors. Most survivors have an ICU stay of >3 weeks.

Nontuberculous mycobacterial infections among patients suspected of pulmonary tuberculosis.

The purpose of this study was to present a retrospective analysis of the frequency of nontuberculous mycobacteria (NTM)-related pulmonary infections among the AFB-positive and/or culture-positive patients in the Warsaw region who were suspected of tuberculosis (TB) and hospitalized in the university hospital between 1999 and 2005. All the AFB-positive pulmonary samples were examined with a molecular method using the Amplicor MTB test (Roche) for detection of Mycobacterium tuberculosis complex, and all mycobacterial isolates were speciated by high performance liquid chromatography (HPLC) analysis of mycolic acids. Patients who met clinical, radiological, and bacteriological criteria of mycobacteriosis were classified according to the American Thoracic Society (ATS) guidelines for diagnosis of NTM related disease. Among the 445 smear-positive or/and culture-positive patients, 142 subjects (31.9%) were found to be infected with M. tuberculosis. Among 303 non-TB patients, mycobacteriosis was found in 27 (8.9%) subjects. The frequency of NTM-related lung disease as compared to the bacteriologically-confirmed lung TB was estimated at 1:5. The rapid, precise methods of NTM speciation are necessary for progress in diagnostics of NTM related diseases.

DIAGNOSTIC UTILITY OF PLEURAL FLUID AND SERUM MARKERS IN DIFFERENTIATION BETWEEN MALIGNANT AND NON-MALIGNANT PLEURAL EFFUSIONS

Study objectiveTo evaluate the diagnostic value of four different tumor markers: cancer antigen 125 (CA-125), carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA 21-1) and neuron specific enolase (NSE) in patients with malignant and non-malignant pleural effusion.Material and methodsOne hundred and two patients with pleural effusion treated in the University Hospital in Warsaw between 2001 and 2003 were studied. They underwent an extensive, diagnostic work-up in order to determine the pleural effusion etiology. Patients with known pleural fluid etiology were labeled as the study group and submitted for further analysis. Pleural fluid and serum samples for CA-125, CEA, CYFRA 21-1 and NSE measurements were collected during the first thoracentesis, centrifuged, and frozen until further use. Pleural fluid and serum concentration of tumor markers were assessed by electrochemiluminescence methods using commercial kits.Results74 patients (32 M, 42 F; mean age 65 ± 14 years) composed the final study group. Exudative pleural effusion was found in 62 patients; of these 36 were malignant (48.6% of all effusions), 20 parapneumonic (or pleural empyema), and 6 tuberculous. In 12 patients, pleural transudate was diagnosed. The highest diagnostic sensitivity for malignant pleural effusion was found for NSE (94.4% and 80.6% in the pleural fluid and serum, respectively). However, the specificity of NSE measurement was relatively low (36.1% and 47.4% in pleural fluid and serum, respectively). The most specific markers of malignant pleural fluid etiology were pleural fluid CYFRA 21-1 and CEA levels (92.1% and 92.1%, respectively). CA-125 was found to be the most specific serum marker of pleural malignancies (78.9%). The AUC for combined pleural markers was 0.89, combined serum markers 0.82, combined ratio pleural/serum markers 0.88.ConclusionsThere are significant differences between the diagnostic value of various pleural fluid and serum markers. Overall, pleural fluid markers are superior to serum markers in determining the pleural fluid etiology. A combination of two or more tumor markers may help improve their diagnostic accuracy. Pleural fluid and serum measurements of different tumor markers play a limited role in the differentiation between malignant and non-malignant pleural effusions.

Short Communication: Subtyping of Mycobacterium kansasii by PCR-Restriction Enzyme Analysis of the hsp65 Gene

Mycobacterium kansasii is one of the most common causes of pulmonary disease resulting from nontuberculous mycobacteria (NTM). It is also the most frequently isolated NTM species from clinical specimens in Poland. The aim of this study was to investigate the distribution of M. kansasii subtypes among patients suspected of having pulmonary NTM disease. Fifty clinical isolates of M. kansasii recovered from as many patients with suspected mycobacterial lung disease between 2000 and 2010 in Poland were genotyped by PCR-restriction enzyme analysis (PCR-REA) of partial hsp65 gene. Mycobacterium kansasii subtype I was the only genotype to be identified among the isolates, both disease-associated and non-disease-associated. Isolation of M. kansasii subtype I from clinical specimens may be indicative of infection but may also merely represent colonization.

Systemic inflammation in peripheral arterial disease with or without coexistent chronic obstructive pulmonary disease: analysis of selected markers

Introduction Low-grade systemic inflammation plays an important role in the pathogenesis and natural history of chronic obstructive pulmonary disease (COPD) and peripheral arterial disease (PAD). The aim of the study was to analyze plasma concentrations of selected markers of inflammation in patients suffering from PAD with or without coexistent COPD. Material and methods Thirty patients (6 women) with advanced PAD (at least IIb stage according to Fontaine scale) hospitalized due to critical limb ischemia were examined. In all patients spirometry was performed to confirm or exclude COPD. Plasma concentration of IL-6, IL-8 and TNF-α was measured using ELISA method. Statistical analysis was performed according to COPD status and according to smoking status independently. Results In the whole group of patients with PAD, COPD was recognized in 14 cases (for the first time in 10 cases). All patients were smokers (46.7% current, 53.3% ex-smokers). We found a significant correlation between FEV1%N (percent of norm of first second expiratory volume) and the number of years of smoking (r = –0.39; p < 0.05). We found similar concentrations of IL-6 (2.54 pg/ml vs. 2.31 pg/ml), IL-8 (8.55 pg/ml vs. 8.14 pg/ml, TNF-α (0.72 pg/ml vs. 1.75 pg/ml) in the COPD(+) group in comparison to the COPD(–) group (differences were not significant). We observed significant positive correlations (p < 0.05) between concentrations of measured markers and significant negative correlations between pain free walking distance and these markers. Conclusions Our study confirmed coexistence of PAD with COPD. The character of inflammation is similar in these smoking-related diseases

Diagnostic Performance of Different Pleural Fluid Biomarkers in Tuberculous Pleurisy

Due to the paucibacillary nature of tuberculous pleural effusion the diagnosis of pleural tuberculosis is challenging. This prospective study was undertaken to evaluate the diagnostic performance of ten different pleural fluid biomarkers in the differentiation between tuberculous and non-tuberculous pleural effusions. Two hundred and three patients with pleural effusion (117 men and 86 women, median age 65 years) were enrolled. Routine diagnostic work-up, including thoracentesis and pleural fluid analysis, was performed to determine the cause of pleural effusion. The following biomarkers were measured in pleural fluid: adenosine deaminase (ADA), interferon gamma (IFN-γ), interleukin 2 soluble receptor (IL-2sRα), sub-unit p40 of interleukin 12b (IL-12p40), interleukin 18 (IL-18), interleukin 23 (IL-23), IFN-γ induced protein 10 kDa (IP-10), Fas-ligand, human macrophage-derived chemokine (MDC) and tumor necrosis factor alfa (TNF-α). There were 44 (21.7%) patients with tuberculous pleural effusion, 88 (43.3%) patients with malignant pleural effusion, 35 (17.2%) with parapneumonic effusion/pleural empyema, 30 (14.8%) with pleural transudates, and 6 (3%) with miscellaneous underlying diseases. Pleural fluid IFN-γ was found the most accurate marker differentiating tuberculous from non-tuberculous pleural effusion, with sensitivity, specificity, PPV, NPV, and AUC 97%, 98%, 95.5%, 99.4%, and 0.99, respectively. Two other biomarkers (IP-10 and Fas ligand) also showed very high diagnostic accuracy with AUC≥0.95. AUC for ADA was 0.92. We conclude that IFN-γ, IP-10, and Fas-ligand in pleural fluid are highly accurate biomarkers differentiating tuberculous from non-tuberculous pleural effusion.

Proposal of a new method for subtyping of Mycobacterium kansasii based upon PCR restriction enzyme analysis of the tuf gene

Within this study, a new, rapid method for subtyping of Mycobacterium kansasii was developed based on the sequence analysis of the tuf gene coding for the Tu (thermo-unstable) elongation factor (EF-Tu). The method involves PCR amplification of ca. 740-bp tuf gene fragment, followed by digestion with the MvaI restriction endonuclease.

Draft Genome Sequences of Mycobacterium kansasii Strains 1010001454, 1010001458, 1010001468, 1010001493, 1010001495, and 1010001469, Isolated from Environmental Sources.

ABSTRACT Mycobacterium kansasii belongs to the nontuberculous mycobacteria (NTM) and causes opportunistic infections with both pulmonary and extrapulmonary manifestations. Here, we report the draft genome sequences of six environmental M. kansasii strains, designated 1010001495 (type I), 1010001469 (type II), 1010001468 (type III), 1010001458 (type IV), 1010001454 (type V), and 1010001493 (type V), originally isolated in five different European countries.

Development and Evaluation of the New Predictive Models in Tuberculous Pleuritis

Different pleural fluid biomarkers have been found useful in the discrimination between tuberculous pleural effusion (TPE) and non-TPE, with interferon gamma (IFN-γ) showing the highest single marker diagnostic accuracy. The aim of the present study was to develop predictive models based on clinical data and pleural fluid biomarkers, other than IFN-γ, which could be applied in differentiating TPE and non-TPE. Two hundred and forty two patients with newly diagnosed pleural effusion were prospectively enrolled. Upon completion of the diagnostic procedures, the underlying disease was identified in 203 patients (117 men and 86 women, median age 65 years; 44 patients with TPE and 159 with non-TPE) who formed the proper study group. Pleural fluid level of ADA, IFN-γ, IL-2, IL-2sRα, IL-12p40, IL-18, IL-23, IP-10, Fas-ligand, MDC, and TNF-α was measured and then ROC analysis and multivariate logistic regression were used to construct the predictive models. Two predictive models with very high diagnostic accuracy (AUC > 0.95) were developed. The first model included body temperature, white blood cell count, pleural fluid ADA and IP-10. The second model was based on age, sex, body temperature, white blood cell count, pleural fluid lymphocyte percentage, and IP-10 level. We conclude that two new predictive models based on clinical and laboratory data demonstrate very high diagnostic performance and can be potentially used in clinical practice to differentiate between TPE and non-TPE.

S Fas in bronchoalveolar lavage fluid of patients with sarcoidosis in relation to cigarette smoking

Sarcoidosis is a multiorgan granulomatous disease with frequent spontaneous remission. Apoptosis is postulated to participate in the granuloma resolution. Soluble Fas (sFas) is known to inhibit Fas-induced apoptosis. The aim of this study was to determine the sFas concentration in the BALf of ever smoking (S) and never smoking (NS) patients with sarcoidosis. We investigated 57 patients with confirmed SA: 36 NS and 21 S. The sFas concentration was measured by ELISA method. The sFas concentration was lower in the BALf of patients S group compared with NS (median values 68.3 vs. 96.1 pg/mL, p=0.07) and it was significantly lower in active smokers when compared with NS (62.9 vs. 96.1 pg/mL, p=0.03). There was a significant correlation between sFas concentration and proportion of lymphocytes and negative relation with macrophage proportion. Lower concentration of sFas in smoking SA patients may result in higher apoptosis rate of inflammatory cells and hereby promote resolution of granulomas.