Person: Bittner, Edward
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Publication Alveolar pentraxin 3 as an early marker of microbiologically confirmed pneumonia: a threshold-finding prospective observational study
(BioMed Central, 2014) Mauri, Tommaso; Coppadoro, Andrea; Bombino, Michela; Bellani, Giacomo; Zambelli, Vanessa; Fornari, Carla; Berra, Lorenzo; Bittner, Edward; Schmidt, Ulrich; Sironi, Marina; Bottazzi, Barbara; Brambilla, Paolo; Mantovani, Alberto; Pesenti, AntonioIntroduction: Timely diagnosis of pneumonia in intubated critically ill patients is rather challenging. Pentraxin 3 (PTX3) is an acute-phase mediator produced by various cell types in the lungs. Animal studies have shown that, during pneumonia, PTX3 participates in fine-tuning of inflammation (for example, microbial clearance and recruitment of neutrophils). We previously described an association between alveolar PTX3 and lung infection in a small group of intubated patients. The aim of the present study was to determine a threshold level of alveolar PTX3 with elevated sensitivity and specificity for microbiologically confirmed pneumonia. Methods: We recruited 82 intubated patients from two intensive care units (San Gerardo Hospital, Monza, Italy, and Massachusetts General Hospital, Boston, MA, USA) undergoing bronchoalveolar lavage (BAL) as per clinical decision. We collected BAL fluid and plasma samples, together with relevant clinical and microbiological data. We assayed PTX3 and soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) in BAL fluid and PTX3, sTREM-1, C-reactive protein (CRP) and procalcitonin (PCT) in plasma. Two blinded independent physicians reviewed patient data to confirm pneumonia. We determined the PTX3 threshold in BAL fluid for pneumonia and compared it to other biomarkers. Results: Microbiologically confirmed pneumonia of bacterial (n =12), viral (n =4) or fungal (n =8) etiology was diagnosed in 24 patients (29%). PTX3 levels in BAL fluid predicted pneumonia with an area under the receiving operator curve of 0.815 (95% CI =0.710 to 0.921, P <0.0001), whereas none of the other biomarkers were effective. In particular, PTX3 levels ≥1 ng/ml in BAL fluid predicted pneumonia in univariate analysis (β =2.784, SE =0.792, P <0.001) with elevated sensitivity (92%), specificity (60%) and negative predictive value (95%). Net reclassification index PTX3 values ≥1 ng/ml in BAL fluid for pneumonia indicated gain in sensitivity and/or specificity vs. all other mediators. These results did not change when we limited our analyses only to confirmed cases of bacterial pneumonia. Moreover, when we considered only the 70 patients who fulfilled the clinical criteria for the diagnosis of pneumonia at BAL fluid sampling, the diagnostic accuracy of PTX levels was confirmed in univariate and ROC curve analysis. Conclusions: In this hypothesis-generating convenience sample, a PTX3 level ≥1 ng/ml in BAL fluid was discriminative of microbiologically confirmed pneumonia in mechanically ventilated patients. Electronic supplementary material The online version of this article (doi:10.1186/s13054-014-0562-5) contains supplementary material, which is available to authorized users.
Publication Delay of transfer from the intensive care unit: a prospective observational study of incidence, causes, and financial impact
(BioMed Central, 2013) Johnson, Daniel W; Schmidt, Ulrich; Bittner, Edward; Christensen, Benjamin; Levi, Retsef; Pino, RichardIntroduction: A paucity of literature exists regarding delays in transfer out of the intensive care unit. We sought to analyze the incidence, causes, and costs of delayed transfer from a surgical intensive care unit (SICU). Methods: An IRB-approved prospective observational study was conducted from January 24, 2010, to July 31, 2010, of all 731 patients transferred from a 20-bed SICU at a large tertiary-care academic medical center. Data were collected on patients who were medically ready for transfer to the floor who remained in the SICU for at least 1 extra day. Reasons for delay were examined, and extra costs associated were estimated. Results: Transfer to the floor was delayed in 22% (n = 160) of the 731 patients transferred from the SICU. Delays ranged from 1 to 6 days (mean, 1.5 days; median, 2 days). The extra costs associated with delays were estimated to be $581,790 during the study period, or $21,547 per week. The most common reasons for delay in transfer were lack of available surgical-floor bed (71% (114 of 160)), lack of room appropriate for infectious contact precautions (18% (28 of 160)), change of primary service (Surgery to Medicine) (7% (11 of 160)), and lack of available patient attendant ("sitter" for mildly delirious patients) (3% (five of 160)). A positive association was found between the daily hospital census and the daily number of SICU beds occupied by patients delayed in transfer (Spearman rho = 0.27; P < 0.0001). Conclusions: Delay in transfer from the SICU is common and costly. The most common reason for delay is insufficient availability of surgical-floor beds. Delay in transfer is associated with high hospital census. Further study of this problem is necessary.