Fiona K. Gibbons

Association of low serum 25-hydroxyvitamin D levels and mortality in the critically ill

Objective:We hypothesized that deficiency in 25-hydroxyvitamin D before hospital admission would be associated with all-cause mortality in the critically ill. Design:Multicenter observational study of patients treated in medical and surgical intensive care units. Setting:A total of 209 medical and surgical intensive care beds in two teaching hospitals in Boston, MA. Patients:A total of 2399 patients, age ≥18 yrs, in whom 25-hydroxyvitamin D was measured before hospitalization between 1998 and 2009. Interventions:None. Measurements and Main Results:Preadmission 25-hydroxyvitamin D was categorized as deficiency in 25-hydroxyvitamin D (≤15 ng/mL), insufficiency (16–29 ng/mL), and sufficiency (≥30 ng/mL). Logistic regression examined death by days 30, 90, and 365 post-intensive care unit admission, in-hospital mortality, and blood culture positivity. Adjusted odds ratios were estimated by multivariable logistic regression models. Preadmission 25-hydroxyvitamin D deficiency is predictive for short-term and long-term mortality. At 30 days following intensive care unit admission, patients with 25-hydroxyvitamin D deficiency have an odds ratio for mortality of 1.69 (95% confidence interval of 1.28–2.23, p < .0001) relative to patients with 25-hydroxyvitamin D sufficiency. 25-Hydroxyvitamin D deficiency remains a significant predictor of mortality at 30 days following intensive care unit admission following multivariable adjustment (adjusted odds ratio of 1.69, 95% confidence interval of 1.26–2.26, p < .0001). At 30 days following intensive care unit admission, patients with 25-hydroxyvitamin D insufficiency have an odds ratio of 1.32 (95% confidence interval of 1.02–1.72, p = .036) and an adjusted odds ratio of 1.36 (95% confidence interval of 1.03–1.79, p = .029) relative to patients with 25-hydroxyvitamin D sufficiency. Results were similar at 90 and 365 days following intensive care unit admission and for in-hospital mortality. In a subgroup analysis of patients who had blood cultures drawn (n = 1160), 25-hydroxyvitamin D deficiency was associated with increased risk of blood culture positivity. Patients with 25-hydroxyvitamin D insufficiency have an odds ratio for blood culture positivity of 1.64 (95% confidence interval of 1.05–2.55, p = .03) relative to patients with 25-hydroxyvitamin D sufficiency, which remains significant following multivariable adjustment (odds ratio of 1.58, 95% confidence interval of 1.01–2.49, p = .048). Conclusion:Deficiency of 25-hydroxyvitamin D before hospital admission is a significant predictor of short- and long-term all-cause patient mortality and blood culture positivity in a critically ill patient population.

Low serum 25-hydroxyvitamin D at critical care initiation is associated with increased mortality

Objective:We hypothesized that deficiency in 25-hydroxyvitamin D at critical care initiation would be associated with all-cause mortalities. Design:Two-center observational study. Setting:Two teaching hospitals in Boston, MA. Patients:The study included 1,325 patients, age ≥18 yrs, in whom 25-hydroxyvitamin D was measured 7 days before or after critical care initiation between 1998 and 2009. Measurements:25-hydroxyvitamin D was categorized as deficiency in 25-hydroxyvitamin D (⩽15 ng/mL), insufficiency (16–29 ng/mL), and sufficiency (≥30 ng/mL). Logistic regression examined death by days 30, 90, and 365 postcritical care initiation and in-hospital mortality. Adjusted odds ratios were estimated by multivariable logistic regression models. Interventions:None. Key Results:25-hydroxyvitamin D deficiency is predictive for short-term and long-term mortality. Thirty days following critical care initiation, patients with 25-hydroxyvitamin D deficiency have an odds ratio for mortality of 1.85 (95% confidence interval 1.15–2.98; p = .01) relative to patients with 25-hydroxyvitamin D sufficiency. 25-hydroxyvitamin D deficiency remains a significant predictor of mortality at 30 days following critical care initiation following multivariable adjustment for age, gender, race, Deyo-Charlson index, sepsis, season, and surgical vs. medical patient type (adjusted odds ratio 1.94; 95% confidence interval 1.18–3.20; p = .01). Results were similarly significant at 90 and 365 days following critical care initiation and for in-hospital mortality. The association between vitamin D and mortality was not modified by sepsis, race, or neighborhood poverty rate, a proxy for socioeconomic status. Conclusion:Deficiency of 25-hydroxyvitamin D at the time of critical care initiation is a significant predictor of all-cause patient mortality in a critically ill patient population.

Red Cell Distribution Width and all cause mortality in critically ill patients

Objective:Red cell distribution width is a predictor of mortality in the general population. The prevalence of increased red cell distribution width and its significance in the intensive care unit are unknown. The objective of this study was to investigate the association between red cell distribution width at the initiation of critical care and all cause mortality. Design:Multicenter observational study. Setting:Two tertiary academic hospitals in Boston, MA. Patients:A total of 51,413 patients, aged ≥18 yrs, who received critical care between 1997 and 2007. Interventions:None. Measurements and Main Results:The exposure of interest was red cell distribution width as a predictor of mortality in the general population. The prevalence of increased red cell distribution width and its significance in the intensive care unit are unknown and categorized a priori in quintiles as ≤13.3%, 13.3% to 14.0%, 14.0% to 14.7%, 14.7% to 15.8%, and >15.8%. Logistic regression examined death by days 30, 90, and 365 postcritical care initiation, inhospital mortality, and bloodstream infection. Adjusted odds ratios were estimated by multivariable logistic regression models. Adjustment included age, sex, race, Deyo–Charlson index, coronary artery bypass grafting, myocardial infarction, congestive heart failure, hematocrit, white blood cell count, mean corpuscular volume, blood urea nitrogen, red blood cell transfusion, sepsis, and creatinine. Red cell distribution width was a particularly strong predictor of all-cause mortality 30 days after critical care initiation with a significant risk gradient across red cell distribution width quintiles after multivariable adjustment: red cell distribution width 13.3% to 14.0% (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.08–1.30; p <.001); red cell distribution width 14.0% to 14.7% (OR, 1.28; 95% CI, 1.16–1.42; p <.001); red cell distribution width 14.7% to 15.8% (OR, 1.69; 95% CI, 1.52–1.86; p <.001); red cell distribution width >15.8% (OR, 2.61; 95% CI, 2.37–2.86; p <.001), all relative to patients with red cell distribution width ≤13.3%. Similar significant robust associations postmultivariable adjustments are seen with death by days 90 and 365 postcritical care initiation as well as inhospital mortality. In a subanalysis of patients with blood cultures drawn (n = 18,525), red cell distribution width at critical care initiation was associated with the risk of bloodstream infection and remained significant after multivariable adjustment. The adjusted risk of bloodstream infection was 1.40- and 1.44-fold higher in patients with red cell distribution width values in the 14.7% to 15.8% and >15.8% quintiles, respectively, compared with those with red cell distribution width ≤13.3%. Estimating the receiver operating characteristic area under the curve shows that red cell distribution width has moderate discriminative power for 30-day mortality (area under the curve = 0.67). Conclusion:Red cell distribution width is a robust predictor of the risk of all-cause patient mortality and bloodstream infection in the critically ill. Red cell distribution width is commonly measured, inexpensive, and widely available and may reflect overall inflammation, oxidative stress, or arterial underfilling in the critically ill.

Imaging Features of Sarcoidosis on MDCT, FDG PET, and PET/CT

OBJECTIVE The objectives of this article are to discuss the epidemiology and natural history of sarcoidosis; to review the classic imaging features of sarcoidosis on radiography, CT, and 67Ga nuclear medicine scans; and to present clinical examples of sarcoidosis as seen on PET and PET/CT in the chest, abdomen and pelvis, and bones. CONCLUSION The imaging features of sarcoidosis are diverse and can be seen on a variety of imaging techniques. It is important for radiologists and nuclear medicine physicians to recognize the common imaging features and patterns of sarcoidosis in order to raise the possibility in the appropriate clinical setting.

Effect of prior exercise on the partitioning of an intestinal glucose load between splanchnic bed and skeletal muscle.

Exercise leads to marked increases in muscle insulin sensitivity and glucose effectiveness. Oral glucose tolerance immediately after exercise is generally not improved. The hypothesis tested by these experiments is that after exercise the increased muscle glucose uptake during an intestinal glucose load is counterbalanced by an increase in the efficiency with which glucose enters the circulation and that this occurs due to an increase in intestinal glucose absorption or decrease in hepatic glucose disposal. For this purpose, sampling (artery and portal, hepatic, and femoral veins) and infusion (vena cava, duodenum) catheters and Doppler flow probes (portal vein, hepatic artery, external iliac artery) were implanted 17 d before study. Overnightfasted dogs were studied after 150 min of moderate treadmill exercise or an equal duration rest period. Glucose ([14C]glucose labeled) was infused in the duodenum at 8 mg/kg x min for 150 min beginning 30 min after exercise or rest periods. Values, depending on the specific variable, are the mean +/- SE for six to eight dogs. Measurements are from the last 60 min of the intraduodenal glucose infusion. In response to intraduodenal glucose, arterial plasma glucose rose more in exercised (103 +/- 4 to 154 +/- 6 mg/dl) compared with rested (104 +/- 2 to 139 +/- 3 mg/dl) dogs. The greater increase in glucose occurred even though net limb glucose uptake was elevated after exercise (35 +/- 5 vs. 20 +/- 2 mg/min) as net splanchnic glucose output (5.1 +/- 0.8 vs. 2.1 +/- 0.6 mg/kg x min) and systemic appearance of intraduodenal glucose (8.1 +/- 0.6 vs. 6.3 +/- 0.7 mg/kg x min) were also increased due to a higher net gut glucose output (6.1 +/- 0.7 vs. 3.6 +/- 0.9 mg/kg x min). Adaptations at the muscle led to increased net glycogen deposition after exercise [1.4 +/- 0.3 vs. 0.5 +/- 0.1 mg/(gram of tissue x 150 min)], while no such increase in glycogen storage was seen in liver [3.9 +/- 1.0 vs. 4.1 +/- 1.1 mg/(gram of tissue x 150 min) in exercised and sedentary animals, respectively]. These experiments show that the increase in the ability of previously working muscle to store glycogen is not solely a result of changes at the muscle itself, but is also a result of changes in the splanchnic bed that increase the efficiency with which oral glucose is made available in the systemic circulation.

Elevation of blood urea nitrogen is predictive of long-term mortality in critically ill patients independent of normal creatinine

Objective:We hypothesized that elevated blood urea nitrogen 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:Twenty intensive care units in two teaching hospitals in Boston, MA. Patients:A total of 26,288 patients, age ≥18 yrs, hospitalized between 1997 and 2007 with creatinine of 0.80–1.30 mg/dL. Interventions:None. Measurements:Blood urea nitrogen at intensive care unit admission was categorized as 10–20, 20–40, and >40 mg/dL. Logistic regression examined death at days 30, 90, and 365 after intensive care unit admission as well as in-hospital mortality. Adjusted odds ratios were estimated by multivariable logistic regression models. Main Results:Blood urea nitrogen at intensive care unit admission was predictive for short- and long-term mortality independent of creatinine. Thirty days following intensive care unit admission, patients with blood urea nitrogen of >40 mg/dL had an odds ratio for mortality of 5.12 (95% confidence interval, 4.30–6.09; p < .0001) relative to patients with blood urea nitrogen of 10–20 mg/dL. Blood urea nitrogen remained a significant predictor of mortality at 30 days after intensive care unit admission following multivariable adjustment for confounders; patients with blood urea nitrogen of >40 mg/dL had an odds ratio for mortality of 2.78 (95% confidence interval, 2.27–3.39; p < .0001) relative to patients with blood urea nitrogen of 10–20 mg/dL. Thirty days following intensive care unit admission, patients with blood urea nitrogen of 20–40 mg/dL had an odds ratio of 2.15 (95% confidence interval, 1.98–2.33; <.0001) and a multivariable odds ratio of 1.53 (95% confidence interval, 1.40–1.68; p < .0001) relative to patients with blood urea nitrogen of 10–20 mg/dL. Results were similar at 90 and 365 days following intensive care unit admission as well as for in-hospital mortality. A subanalysis of patients with blood cultures (n = 7,482) demonstrated that blood urea nitrogen at intensive care unit admission was associated with the risk of blood culture positivity. Conclusion:Among critically ill patients with creatinine of 0.8–1.3 mg/dL, an elevated blood urea nitrogen was associated with increased mortality, independent of serum creatinine.

Association of low serum 25-hydroxyvitamin D levels and acute kidney injury in the critically ill*

Objective:Given the importance of inflammation in acute kidney injury and the relationship between vitamin D and inflammation, we sought to elucidate the effect of vitamin D on acute kidney injury. We hypothesized that deficiency in 25-hydroxyvitamin D prior to hospital admission would be associated with acute kidney injury in the critically ill. Design:Two-center observational study of patients treated in medical and surgical intensive care units. Setting:Two hundred nine medical and surgical intensive care beds in two teaching hospitals in Boston, Massachusetts. Patients:Two thousand seventy-five patients, aged ≥18 yrs, in whom serum 25-hydroxyvitamin D was measured prior to hospitalization between 1998 and 2009. Interventions:None. Measurements and Main Results:The exposure of interest was preadmission serum 25-hydroxyvitamin D and categorized a priori as deficiency (25-hydroxyvitamin D <15 ng/mL), insufficiency (25-hydroxyvitamin D 15–30 ng/mL), or sufficiency (25-hydroxyvitamin D ≥30 ng/mL). The primary outcome was acute kidney injury defined as meeting Risk, Injury, Failure, Loss, and End-stage kidney disease (RIFLE) Injury or Failure criteria. Logistic regression examined the RIFLE criteria outcome. Adjusted odds ratios were estimated by multivariate logistic regression models. Preadmission 25-hydroxyvitamin D deficiency is predictive of acute kidney injury. Patients with 25-hydroxyvitamin D deficiency have an odds ratio for acute kidney injury of 1.73 (95% confidence interval 1.30–2.30; p < .0001) relative to patients with 25-hydroxyvitamin D sufficiency. 25-Hydroxyvitamin D deficiency remains a significant predictor of acute kidney injury following multivariable adjustment (adjusted odds ratio 1.50; 95% confidence interval 1.42–2.24; p < .0001). Patients with 25-hydroxyvitamin D insufficiency have an odds ratio for acute kidney injury of 1.49 (95% confidence interval 1.15–1.94; p = .003) and an adjusted odds ratio of 1.23 (95% confidence interval 1.12–1.72; p = .003) relative to patients with 25-hydroxyvitamin D sufficiency. In addition, preadmission 25-hydroxyvitamin D deficiency is predictive of mortality. Patients with 25-hydroxyvitamin D insufficiency have an odds ratio for 30-day mortality of 1.60 (95% confidence interval 1.18–2.17; p = .003) and an adjusted odds ratio of 1.61 (95% confidence interval 1.06–1.57; p = .004) relative to patients with 25-hydroxyvitamin D sufficiency. Conclusion:Deficiency of 25-hydroxyvitamin D prior to hospital admission is a significant predictor of acute kidney injury and mortality in a critically ill patient population.

Evidence for a U-shaped relationship between prehospital vitamin D status and mortality: a cohort study.

OBJECTIVE The objective of the study was to examine the association between prehospital serum 25-hydroxyvitamin D [25(OH)D]and the risk of mortality after hospital admission. DESIGN We performed a retrospective cohort study of adults hospitalized for acute care between 1993 and 2011. SETTING The study was conducted at two Boston teaching hospitals. PATIENTS A total of 24,094 adult inpatients participated in the study. INTERVENTION There was no intervention. MEASUREMENTS All patients had serum 25(OH)D measured before hospitalization. The exposure of interest was 25(OH)D categorized as less than 10 ng/mL, 10-19.9 ng/mL, 20-29.9 ng/mL, 30-49.9 ng/mL, 50-59.9 ng/mL, 60-69.9 ng/mL, and 70 ng/mL or greater. The main outcome measure was 90-day mortality. Adjusted odds ratios (ORs) were estimated by multivariable logistic regression with inclusion of potential confounders. RESULTS After adjustment for age, gender, race (white vs nonwhite), patient type (surgical vs medical), season of 25(OH)D draw, and the Deyo-Charlson index, patients with 25(OH)D levels less than 30 ng/mL or 60 ng/mL or greater had higher odds of 90-day mortality compared with patients with levels of 30-49.9 ng/mL [adjusted OR (95% confidence interval) for 25(OH)D <10 ng/mL, 10-19.9 ng/mL, 20-29.9 ng/mL, 50-59.9 ng/mL, 60-69.9 ng/mL, and ≥70 ng/mL was 2.01 (1.68-2.40), 1.89 (1.64-2.18), 1.34 (1.16-1.56), 0.94 (0.69-1.26), 1.52 (1.03-2.25), and 1.69 (1.09-2.61), respectively, compared with patients with 25(OH)D levels 30-49.9 ng/mL]. LIMITATIONS A causal relationship between either low or high 25(OH)D levels and increased mortality can not necessarily be inferred from this observational study. CONCLUSIONS Analysis of 24 094 adult patients showed that 25(OH)D levels less than 20 ng/mL and 60 ng/mL or greater before hospitalization were associated with an increased odds of 90-day mortality. Although previous reports have suggested an association between low vitamin D status and mortality, these data raise the issue of potential harm from high serum 25(OH)D levels, provide a rationale for an upper limit to supplementation, and emphasize the need for caution in the use of extremely high doses of vitamin D among patients.

Neighborhood Poverty Rate and Mortality in Patients Receiving Critical Care in the Academic Medical Center Setting

BACKGROUND Poverty is associated with increased risk of chronic illness but its contribution to critical care outcome is not well defined. METHODS We performed a multicenter observational study of 38,917 patients, aged ≥ 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 = .2); 10% to 20% OR, 0.96 (95% CI, 0.87-1.06; P = .5); 20% to 40% OR, 1.08 (95% CI, 0.96-1.22; P = .2); > 40% OR, 1.20 (95% CI, 0.90-1.60; P = .2); referent in each is < 5%. Similar nonsignificant 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-year-postdischarge 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.

The association of red cell distribution width at hospital discharge and out-of-hospital mortality following critical illness*.

Objectives:Red cell distribution width is associated with mortality and bloodstream infection risk in the critically ill. In hospitalized patients with critical illness, it is not known if red cell distribution width can predict subsequent risk of all-cause mortality following hospital discharge. We hypothesized that an increase in red cell distribution width at hospital discharge in patients who survived to discharge following critical care would be associated with increased postdischarge mortality. Design:Two-center observational cohort study Setting:All medical and surgical ICUs at the Brigham and Women’s Hospital and Massachusetts General Hospital. Patients:We studied 43,212 patients, who were 18 years old or older and received critical care between 1997 and 2007 and survived hospitalization. Interventions:None. Measurements and Main Results:The exposure of interest was red cell distribution width within 24 hours of hospital discharge and categorized a priori in quintiles as less than or equal to 13.3%, 13.3–14.0%, 14.0–14.7%, 14.7–15.8%, and more than 15.8%. The primary outcome was all-cause mortality in the 30 days following hospital discharge. Secondary outcomes included 90-day and 365-day mortality following hospital discharge. Mortality was determined using the U.S. Social Security Administration Death Master File, and 365-day follow-up was present in all cohort patients. Adjusted odds ratios were estimated by multivariable logistic regression models with inclusion of covariate terms thought to plausibly interact with both red cell distribution width and mortality. Adjustment included age, race, gender, Deyo-Charlson Index, patient type (medical vs surgical), sepsis, and number of organs with acute failure. In patients who received critical care and survived hospitalization, the discharge red cell distribution width was a robust predictor of all-cause mortality and remained so following multivariable adjustment. Patients with a discharge red cell distribution width of 14.0–14.7%, 14.7–15.8%, and more than 15.8% have an odds ratio for mortality in the 30 days following hospital discharge of 2.86 (95% CI, 2.25–3.62), 4.57 (95% CI, 3.66–5.72), and 8.80 (95% CI, 7.15–10.83), respectively, all relative to patients with a discharge red cell distribution width less than or equal to 13.3%. Following multivariable adjustment, patients with a discharge red cell distribution width of 14.0–14.7%, 14.7–15.8%, and more than 15.8% have an odds ratio for mortality in the 30 days following hospital discharge of 1.63 (95% CI, 1.27–2.07), 2.36 (95% CI, 1.87–2.97), and 4.18 (95% CI, 3.36–5.20), respectively, all relative to patients with a discharge red cell distribution width less than or equal to 13.3%. Similar significant robust associations post multivariable adjustments are seen with death by days 90 and 365 postdischarge. Estimating the receiver-operating characteristic area under the curve shows that discharge red cell distribution width has moderate discriminative power for mortality 30 days following hospital discharge (area under the curve = 0.70; SE 0.006; 95% CI, 0.69–0.71; p < 0.0001). Conclusion:In patients treated with critical care who survive hospitalization, an elevated red cell distribution width at the time of discharge is a robust predictor of subsequent all-cause patient mortality. Increased discharge red cell distribution width likely reflects the presence of proinflammatory state, oxidative stress, arterial underfilling, or a combination, thereof which may explain the observed impact on patient survival following discharge. Elevated red cell distribution width at hospital discharge may identify ICU survivors who are at risk for adverse outcomes following hospital discharge.