An Integrated Clinico-Metabolomic Model Improves Prediction of Death in Sepsis

Sepsis is a common cause of death, but outcomes in individual patients are difficult to predict. Elucidating the molecular processes that differ between sepsis patients who survive and those who die may permit more appropriate treatments to be deployed. We examined the clinical features, and the plasma metabolome and proteome of patients with and without community-acquired sepsis, upon their arrival at hospital emergency departments and 24 hours later. The metabolomes and proteomes of patients at hospital admittance who would die differed markedly from those who would survive. The different profiles of proteins and metabolites clustered into fatty acid transport and β-oxidation, gluconeogenesis and the citric acid cycle. They differed consistently among several sets of patients, and diverged more as death approached. In contrast, the metabolomes and proteomes of surviving patients with mild sepsis did not differ from survivors with severe sepsis or septic shock. An algorithm derived from clinical features together with measurements of seven metabolites predicted patient survival. This algorithm may help to guide the treatment of individual patients with sepsis

Metabolomic derangements are associated with mortality in critically ill adult patients

Objective: To identify metabolomic biomarkers predictive of Intensive Care Unit (ICU) mortality in adults. Rationale: Comprehensive metabolomic profiling of plasma at ICU admission to identify biomarkers associated with mortality has recently become feasi

Airway dilation in bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation

SummaryRationaleBronchiolitis obliterans syndrome (BOS) is a late, non-infectious pulmonary complication following hematopoietic stem cell transplantation (HSCT). There is minimal data published on quantitative radiologic characterization of airway remodeling in these subjects.ObjectivesTo examine quantitative measurements of airway morphology and their correlation with lung function in a cohort of patients who underwent HSCT and developed BOS.MethodsAll adult patients who underwent allogeneic HSCT at the Dana-Farber Cancer Institute/Brigham and Women's Hospital (n = 1854) between January 1st 2000 and June 30th 2010 were screened for the development of BOS. Clinically acquired high resolution CT (HRCT) scans of the chest were collected. For each subjects discrete measures of airway wall area were performed and the square root of wall area of a 10-mm luminal perimeter (Pi10) was calculated.Measurements and main resultsWe identified 88 cases of BOS, and 37 of these patients had available HRCT. On CT scans obtained after BOS diagnosis, the Pi10 decreased (consistent with airway dilation) as compared with pre-BOS values (p < 0.001). After HSCT the Pi10 correlated with FEV1% predicted (r = 0.636, p < 0.0001), and RV/TLC% predicted (r = −0.736, p < 0.0001), even after adjusting for age, sex and total lung capacity (p < 0.0001 for both).ConclusionsOn HRCT scan BOS is characterized by central airway dilation, the degree of which is correlated to decrements in lung function. This is opposite of what has been previously demonstrated in COPD and asthma that quantitative measure of proximal airway wall thickening directly correlate with pulmonary function. Our data suggests that the pathologic process affecting the central airways is different from the pathology observed in the distal airways. Further work is needed to determine if such change can be used as a sensitive and specific tool for the future diagnosis and staging of BOS

Low Dose Busulfan Is Associated with Bronchiolitis Obliterans Syndrome Following Allogeneic Hematopoietic Stem Cell Transplantation.

Abstract Abstract 3128 Rationale: Bronchiolitis obliterans syndrome (BOS) is the most common late non-infectious pulmonary complication following hematopoietic stem cell transplantation (HSCT). The prevalence is estimated to be between 5–10% after allogeneic HSCT with a significant increase in morbidity and mortality. We conducted a retrospective case control study to evaluate the associations between patients with BOS and those who did not develop airflow obstruction or symptoms. Methods: Between January 1st 2000 and June 30th 2010 all patients who underwent an allogeneic HSCT at the Dana-Farber Cancer Institute/Brigham and Women's Hospital (n=1854) were screened for the development of BOS, using a modified NIH diagnostic criteria. BOS was defined as 1) new onset airflow obstruction, FEV1/FVC ratio ≤0.7 and FEV1 &lt;80% predicted; 2) irreversible obstruction defined as no response to bronchodilator per ATS criteria; 3) if airflow obstruction was noted prior to HSCT, a ≥15% decline in FEV1 from baseline; 4) BO confirmed by pathology irrespective of meeting the spirometric definition of BOS. We matched the BOS cases, based on date of HSCT (±90 days), with 2 groups of control subjects: 1) subjects who developed chronic graft vs. host disease (cGVHD) without BOS and 2) subjects who developed neither cGVHD nor BOS. Comparisons between BOS subjects and controls were conducted using t-test or Fisher's exact tests. We also performed a multivariate regression analysis predicting the development of BOS; all variables with a p &lt;0.1 on univariate analysis were included in the model. All statistical analyses were performed using R. Results: We identified 89 subjects meeting our diagnostic criteria for BOS with a prevalence of 4.8%. The median time from transplantation to meeting criteria for BOS was 491 days (range: 48–2067). Univariate analysis demonstrated that BOS was significantly associated with previously reported risk factors including age, pre-transplantation PFT's, high risk disease, source of peripheral blood stem cells, unrelated donor, history of respiratory infection prior to day 100, and busulfan based conditioning regimens. (all p&lt;0.05, table 1). Upon further stratification of regimens, univariate analysis demonstrated that reduced intensity conditioning busulfan was associated with the development of BOS (p&lt;0.001). After analyzing our univariate associations in a multivariate model, busulfan-based conditioning and unrelated donors were independent factors associated with BOS (p &lt;0.001), while, ATG use conferred lower odds of BOS (p&lt;0.001). Conclusion: Our findings extend those from prior reports of risk factors associated with BOS. Our results demonstrate that busulfan, even when used at lower doses in reduced intensity conditioning transplantation, confers an increased risk for BOS. Future studies in prospective cohorts will be important to confirm these findings. Disclosures: No relevant conflicts of interest to declare. </jats:sec