Red Cell Distribution Width (RDW) is a predictor of mortality in the general population. The prevalence of increased RDW and its significance in the intensive care unit are unknown. Objective To investigate the association between RDW at the initiation of critical care and all cause mortality Design Multicenter observational study Setting Two tertiary academic hospitals in Boston, Massachusetts Patients 51,413 patients, age ≥ 18 years, who received critical care between 1997 and 2007 Measurements The exposure of interest was RDW and categorized a priori in quintiles as ≤13.3%, 13.3–14.0%, 14.0–14.7%, 14.7–15.8%, and >15.8%. Logistic regression examined death by days 30, 90 and 365 post-critical care initiation, in-hospital mortality and bloodstream infection. Adjusted odds ratios were estimated by multivariable logistic regression models. Adjustment included age, sex, race, Deyo-Charlson index, CABG, MI, CHF, hematocrit, WBC, MCV, BUN, red blood cell transfusion, sepsis and creatinine. Interventions None Key Results RDW was a particularly strong predictor of all cause mortality 30 days following critical care initiation with a significant risk gradient across RDW quintiles following multivariable adjustment: RDW 13.3–14.0% OR 1.19 (95% CI, 1.08–1.30; P<0.001); RDW 14.0–14.7% OR 1.28 (95% CI, 1.16–1.42; P<0.001); RDW 14.7–15.8% OR 1.69 (95% CI, 1.52–1.86; P<0.001); RDW > 15.8% OR 2.61 (95% CI, 2.37–2.86; P<0.001); all relative to patients with RDW ≤13.3%. Similar significant robust associations post multivariable adjustments are seen with death by days 90 and 365 post-critical care initiation as well as in-hospital mortality. In a sub-analysis of patients with blood cultures drawn (n= 18,525), RDW at critical care initiation was associated with the risk of bloodstream infection and remained significant following multivariable adjustment. The adjusted risk of bloodstream infection was 1.40- and 1.44-fold higher in patients with RDW values in the 14.7–15.8% and >15.8% quintiles, respectively, compared with those with RDW ≤13.3%. Estimating the ROC AUC shows that RDW has moderate discriminative power for 30-day mortality (AUC = 0.67). Conclusion RDW is a robust predictor of the risk of all cause patient mortality and bloodstream infection in the critically ill. RDW is commonly measured, inexpensive and widely available and may reflect overall inflammation, oxidative stress, or arterial underfilling in the critically ill.

Objective We hypothesized that elevated BUN can be associated with all cause mortality independent of creatinine in a heterogeneous critically ill population. Design Multicenter observational study of patients treated in medical and surgical intensive care units. Setting 20 intensive care units in two teaching hospitals in Boston, Massachusetts Patients 26,288 patients, age ≥ 18 years, hospitalized between 1997 and 2007 with creatinine 0.80–1.30 mg/dl. Measurements BUN at ICU admission was categorized as 10–20, 20–40 and >40 mg/dl. Logistic regression examined death at days 30, 90 and 365 post-ICU admission as well as in hospital mortality. Adjusted odds ratios were estimated by multivariable logistic regression models. Interventions None Key Results BUN at ICU admission is predictive for short term and long term mortality independent of creatinine. 30 days following ICU admission, patients with BUN >40 mg/dl have an Odds Ratio for mortality of 5.12 (95% CI, 4.30–6.09; P<.0001) relative to patients with BUN 10–20 mg/dl. BUN remains a significant predictor of mortality at 30 days following ICU admission following multivariable adjustment for confounders, patients with BUN >40 mg/dl have an Odds Ratio for mortality of 2.78 (95% CI, 2.27–3.39; P<.0001) relative to patients with BUN 10–20 mg/dl. 30 days following ICU admission, patients with BUN 20–40 mg/dl have an OR of 2.15 (95% CI, 1.98–2.33; <.0001) and a multivariable OR of 1.53 (95% CI, 1.40–1.68; P<.0001) relative to patients with BUN 10–20 mg/dl. Results were similar at 90 and 365 days following ICU admission as well as in-hospital mortality. A subanalysis of patients with blood cultures (n= 7,482), demonstrated that BUN at ICU admission was associated with the risk of blood culture positivity. Conclusion Among critically ill patients with Cr 0.8–1.3 mg/dl, an elevated BUN is associated with increased mortality, independent of serum creatinine.

Virus-specific cytotoxic T lymphocytes (CTL) exert intense selection pressure on replicating simian immunodeficiency virus (SIV) and human immunodeficiency virus type 1 (HIV-1) in infected individuals. The immunodominant Mamu-A * 01-restricted Gag p11C, C-M epitope is highly conserved among all sequenced isolates of SIV and therefore likely is structurally constrained. The strategies used by virus isolates to mutate away from an immunodominant epitope-specific CTL response are not well defined. Here we demonstrate that the emergence of a position 2 p11C, C-M epitope substitution (T47I) in a simian-human immunodeficiency virus (SHIV) strain 89.6P-infected Mamu-A * 01 ؉ monkey is temporally correlated with the emergence of a flanking isoleucine-to-valine substitution at position 71 (I71V) of the capsid protein. An analysis of the SIV and HIV-2 sequences from the Los Alamos HIV Sequence Database revealed a significant association between any position 2 p11C, C-M epitope mutation and the I71V mutation. The T47I mutation alone is associated with significant decreases in viral protein expression, infectivity, and replication, and these deficiencies are restored to wild-type levels with the introduction of the flanking I71V mutation. Together, these data suggest that a compensatory mutation is selected for in SHIV strain 89.6P to facilitate the escape of that virus from CTL recognition of the dominant p11C, C-M epitope.

Socioeconomic status (SES) is an important determinant of health and mortality. 1,2 An inverse and stepwise relationship between SES and mortality exists. [3][4][5] Differences in rates of mortality, comorbidities, and disability are closely linked to SES. 1 Those who have an advanced education, have well-paying jobs, and live in neighborhoods with low poverty have a higher life expectancy and lower comorbidities. 1 The mechanism for these observations is unclear. It is postulated that immune-system function may respond to the increased psychosocial stress of low Background: Poverty is associated with increased risk of chronic illness but its contribution to critical care outcome is not well defi ned. Methods: We performed a multicenter observational study of 38,917 patients, aged Ն 18 years, who received critical care between 1997 and 2007. The patients were treated in two academic medical centers in Boston, Massachusetts. Data sources included 1990 US census and hospital administrative data. The exposure of interest was neighborhood poverty rate, categorized as , 5%, 5% to 10%, 10% to 20%, 20% to 40% and . 40%. Neighborhood poverty rate is the percentage of residents below the federal poverty line. Census tracts were used as the geographic units of analysis. Logistic regression examined death by days 30, 90, and 365 post-critical care initiation and in-hospital mortality. Adjusted ORs were estimated by multivariable logistic regression models. Sensitivity analysis was performed for 1-year postdischarge mortality among patients discharged to home. Results: Following multivariable adjustment, neighborhood poverty rate was not associated with all-cause 30-day mortality: 5% to 10% OR, 1.05 (95% CI, 0.98-1.14; P 5 .2); 10% to 20% OR, 0.96 (95% CI, 0.87-1.06; P 5 .5); 20% to 40% OR, 1.08 (95% CI, 0.96-1.22; P 5 .2); . 40% OR, 1.20 (95% CI, 0.90-1.60; P 5 .2); referent in each is , 5%. Similar nonsignifi cant associations were noted at 90-day and 365-day mortality post-critical care initiation and in-hospital mortality. Among patients discharged to home, neighborhood poverty rate was not associated with 1-yearpostdischarge mortality. Conclusions: Our study suggests that there is no relationship between the neighborhood poverty rate and mortality up to 1 year following critical care at academic medical centers.CHEST 2011; 139(6):1368-1379