Clinical impact of pulmonary sampling site in the diagnosis of ventilator-associated pneumonia: A prospective study using bronchoscopic bronchoalveolar lavage

PurposeIt is unclear whether ventilator-associated pneumonia (VAP) is actually a bilateral and multifocal process. In addition, the diagnostic role of chest x-ray is under debate. Assuming a low microbiologic concordance between the left and right lungs, the reliability of a single pulmonary sampling becomes questionable. The purpose of this study was to determine whether the choice of the pulmonary sampling area is clinically relevant in the management of VAP.MethodsIn 79 patients admitted to a university general intensive care unit with clinically suspected VAP, right- and left-lung bronchoalveolar lavage (BAL) samples were taken with separate bronchoscopes and quantitatively cultured. Primary end-point variable was microbiologic concordance rate between right- and left-lung BAL cultures. Secondary outcomes included predictors of microbiologic concordance, rates of appropriate antibiotic treatment, and diagnostic accuracy of chest x-ray.ResultsBAL cultures were bilaterally negative in 21 (27%) of 79 patients, bilaterally positive in 36 (46%), and unilaterally positive (right in 12, left in 10) in 22 (28%). Intra-patient concordance was observed in 47 (59.5%) of 79 cases and independently associated with purulent secretions and bilateral infiltrates on chest x-ray. In simulated prescribing experiments, treatments chosen based on right or left cultures alone were as appropriate as those based on bilateral data in > 90% of cases. The presence of a radiographic infiltrate in the sampling area predicted BAL culture positivity with a positive predictive value of only 61%.ConclusionsIn patients with clinically suspected VAP (especially those without purulent secretions or without radiographically documented bilateral infiltrates), quantitative culture of a single BAL sample may provide an incomplete assessment of lung microbiology, without having a relevant impact on the appropriateness of antimicrobial treatment. These findings suggest that single sampling of respiratory secretions, regardless radiographic opacity, seems to be a reliable diagnostic method in the management of VAP.     

Refractory or relapsed aggressive B-cell lymphoma failing (R)-CHOP: an analysis of patients treated on the RICOVER-60 trial

BackgroundThe prognosis of elderly patients with aggressive B-non-Hodgkin’s lymphoma after first lymphoma-related treatment failure (TF-L) is not well described.MethodsWe analysed patient characteristics including the presence of MYC rearrangements and MYC-expression immunohistochemistry (IHC) at diagnosis and modalities of salvage therapy and their impact on the prognosis of patients between 61 and 80 years who had been treated on the RICOVER-60 trial.ResultsTF-L occurred in 301 of the 1222 (24.6%) patients; 297 patients could be analysed. Prognosis was extremely poor in patients with primary progressive disease or early relapse (≤12 months) with median survivals of 3.3 and 6.4 months. Survival after TF-L was significantly lower in patients pretreated with R-CHOP compared with CHOP (23.0% versus 36.4% at 2 years, P = 0.016). In patients with MYC translocation at diagnosis Rituximab reduced the risk of TF-L from 58.8% to 26.3%. Survival after TF-L was significant longer for patients after CHOP without MYC translocations (31.8% versus 0% at 2 years, P < 0.001) or negative MYC-IHC (41.0% versus 16.8% at 2 years, P = 0.017) but not after R-CHOP. 224 patients (75.4%) received salvage therapy. Rituximab was part of salvage therapy in 57.4% and improved 2-year survival rate from 20.7% to 46.8% (P < 0.001). The benefit of R was significant after first-line CHOP [2-year overall survival (OS) 49.6% versus 19.1%, P < 0.001] as well as after R-CHOP (2-year OS 33.1% and 22.5%, P = 0.034). For patients pretreated with R-CHOP long-term survival was below 15% regardless of the treatment chosen.ConclusionMYC rearrangement and IHC are adverse prognostic factors after TF-L for CHOP treated patients, rituximab as part of first-line therapy reduced the effects of MYC-break. Rituximab improves results of any type of salvage therapy; however, survival after progression/relapse of aggressive B-cell lymphoma in elderly patients pretreated with (R)-CHOP is poor regardless of treatment chosen.     

Hierarchical Bayesian cognitive processing models to analyze clinical trial data

Identifying disease-modifying treatment effects in earlier stages of Alzheimer's disease (AD)—when changes are subtle—will require improved trial design and more sensitive analytical methods. We applied hierarchical Bayesian analysis with cognitive processing (HBCP) models to the Alzheimer's Disease Assessment Scale—Cognitive subscale (ADAS-Cog) and MCI (mild cognitive impairment) Screen word list memory task data from 14 Alzheimer's disease AD patients of the Myriad Pharmaceuticals' phase III clinical trial of Flurizan (a γ-secretase modulator) versus placebo. The original analysis of 1649 patients found no treatment group differences. HBCP analysis and the original ADAS-Cog analysis were performed on the small sample. HBCP analysis detected impaired memory storage during delayed recall, whereas the original ADAS-Cog analytical method did not. The HBCP model identified a harmful treatment effect in a small sample, which has been independently confirmed from the results of other γ-secretase inhibitor. The original analytical method applied to the ADAS-Cog data did not detect this harmful treatment effect on either the full or the small sample. These findings suggest that HBCP models can detect treatment effects more sensitively than currently used analytical methods required by the Food and Drug Administration, and they do so using small patient samples.