IntroductionSevere hypoglycemia (blood glucose concentration (BG) < 40 mg/dL) is independently associated with an increased risk of mortality in critically ill patients. The association of milder hypoglycemia (BG < 70 mg/dL) with mortality is less clear.MethodsProspectively collected data from two observational cohorts in the USA and in The Netherlands, and from the prospective GLUCONTROL trial were analyzed. Hospital mortality was the primary endpoint.ResultsWe analyzed data from 6,240 patients: 3,263 admitted to Stamford Hospital (ST), 2,063 admitted to three institutions in The Netherlands (NL) and 914 who participated in the GLUCONTROL trial (GL). The percentage of patients with hypoglycemia varied from 18% to 65% among the different cohorts. Patients with hypoglycemia experienced higher mortality than did those without hypoglycemia even after stratification by severity of illness, diagnostic category, diabetic status, mean BG during intensive care unit (ICU) admission and coefficient of variation (CV) as a reflection of glycemic variability. The relative risk (RR, 95% confidence interval) of mortality associated with minimum BG < 40, 40 to 54 and 55 to 69 mg/dL compared to patients with minimum BG 80 to 109 mg/dL was 3.55 (3.02 to 4.17), 2.70 (2.31 to 3.14) and 2.18 (1.87 to 2.53), respectively (all P < 0.0001). The RR of mortality associated with any hypoglycemia < 70 mg/dL was 3.28 (2.78 to 3.87) (P < 0.0001), 1.30 (1.12 to 1.50) (P = 0.0005) and 2.11 (1.62 to 2.74) (P < 0.0001) for the ST, NL and GL cohorts, respectively. Multivariate regression analysis demonstrated that minimum BG < 70 mg/dL, 40 to 69 mg/dL and < 40 mg/dL were independently associated with increased risk of mortality for the entire cohort of 6,240 patients (odds ratio (OR) (95% confidence interval (CI)) 1.78 (1.39 to 2.27) P < 0.0001), 1.29 (1.11 to 1.51) P = 0.0011 and 1.87 (1.46 to 2.40) P < 0.0001) respectively.ConclusionsMild hypoglycemia was associated with a significantly increased risk of mortality in an international cohort of critically ill patients. Efforts to reduce the occurrence of hypoglycemia in critically ill patients may reduce mortality

We have developed a limiting-dilution assay of long-term repopulating hematopoietic stem cells in the mouse using a miniturized stroma- dependent bone marrow culture assay in vitro. The cells were overlaid on irradiated stromal layers in microtiter wells in a range of concentrations, and frequencies of cobblestone area-forming cells (CAFC) were calculated by employing Poisson statistics. The production of secondary granulocyte/macrophage colony-forming units (CFU-G/M) in the adherent layer of individual wells was correlated with the presence of such cobblestone areas. CAFC frequencies were determined in bone marrow cell suspensions that were either enriched for marrow repopulating ability (MRA) in vivo, while depleted for spleen colony- forming units (CFU-S), or vice versa. The separation of bone marrow cells (BMC) was either based on centrifugal elutriation, or monoclonal antibody-mediated magnetic depletion of cells carrying cell surface differentiation antigens, and subsequent sorting on the basis of light scatter and rhodamine-123 retention as a measure of mitochondrial activity. In addition, 5-fluorouracil-resistant BMC were studied. Our investigations show that a time-dependent cobblestone area formation exists that reflects the turnover time and primitiveness of CAFC. The frequency of precursors forming cobblestone areas on day 28 after overlay is proposed to be a measure for MRA, whereas the day-7 CAFC frequency closely corresponds with day-12 CFU-S numbers in the suspensions tested.

BackgroundHypoglycemia is associated with increased mortality in critically ill patients. The impact of hypoglycemia on resource utilization has not been investigated. The objective of this investigation was to evaluate the association of hypoglycemia, defined as a blood glucose concentration (BG) < 70 mg/dL, and intensive care unit (ICU) length of stay (LOS) in three different cohorts of critically ill patients.MethodsThis is a retrospective investigation of prospectively collected data, including patients from two large observational cohorts: 3,263 patients admitted to Stamford Hospital (ST) and 2,063 patients admitted to three institutions in The Netherlands (NL) as well as 914 patients from the GLUCONTROL trial (GL), a multicenter prospective randomized controlled trial of intensive insulin therapy.ResultsPatients with hypoglycemia were more likely to be diabetic, had higher APACHE II scores, and higher mortality than did patients without hypoglycemia. Patients with hypoglycemia had longer ICU LOS (median [interquartile range]) in ST (3.0 [1.4-7.1] vs. 1.2 [0.8-2.3] days, P < 0.0001), NL (5.2 [2.6-10.3] vs. 2.0 [1.3-3.2] days, P < 0.0001), and GL (9 [5-17] vs. 5 [3-9] days, P < 0.0001). For the entire cohort of 6,240 patients ICU LOS was 1.8 (1.0-3.3) days for those without hypoglycemia and 3.0 (1.5-6.7) days for those with a single episode of hypoglycemia (P < 0.0001). This was a consistent finding even when patients were stratified by severity of illness or survivor status. There was a strong positive correlation between the number of episodes of hypoglycemia and ICU LOS among all three cohorts.ConclusionsThis multicenter international investigation demonstrated that hypoglycemia was consistently associated with significantly higher ICU LOS in heterogeneous cohorts of critically ill patients, independently of severity of illness and survivor status. More effective methods to prevent hypoglycemia in these patients may positively impact their cost of care.

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