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Purpose: To compare the effects of predominantly hydroxyethyl starch (HES 6% 130/0.4)-based with predominantly gelatin 4%-based fluid therapy on renal function in surgical intensive care unit (ICU) patients.Methods: Before-after, retrospective, study of surgical ICU patients. All patients admitted from January to June 2005 formed the HES group, with HES 130/0.4 as the standard colloid of choice. All patients admitted from January to June 2006 formed the GEL group, with gelatin 4% as the primary colloid. Acute renal failure (ARF) was defined as new need for renal replacement therapy (RRT) or at least a two-fold increase in baseline creatinine.Results: There were 1383 patients in the HES group and 1528 in the GEL group; 118 and 87, in each group respectively, had severe sepsis. The incidence of ARF and ICU and hospital mortality rates were similar in the two groups. In a post-hoc multivariable analysis, cumulative doses >33 ml/kg of either HES (OR = 1.85, 95% CI: 1.01-3.41, p < 0.001) or gelatin (OR = 1.99, 95% CI: 1.05-3.79, p = 0.035) were associated with a higher risk of ARF.Conclusions: The incidence of ARF was similar in patients who received predominantly HES (6% 130/.04) fluid therapy and in those who received predominantly gelatin 4%. Moderate cumulative doses of modern HES or gelatin solutions may be associated with a higher risk of ARF. [ABSTRACT FROM AUTHOR]

Objective: We developed a model for direct assessment of BMC sequestration in the postischemic murine myocardium after direct antegrade intracoronary injection., Methods: Modified syngeneic heterotopic heart transplantation was used as a basic model for global myocardial I/R injury in a total of n = 29 animals. IVM was employed to analyze the right ventricular subepicardial coronary microcirculation and for tracking fluorescently labeled BMCs., Results: IVM allowed monitoring all segments of the coronary microcirculation including feeding arterioles, nutritive capillaries, and postcapillary venules. WI and generalized atherosclerosis induced profound reperfusion failure, particularly in nutritive myocardial capillaries. BMCs were found to exclusively sequester in myocardial capillaries, but not in coronary arterioles or postcapillary venules. The sequestration of BMCs in coronary capillaries occurred independent of WI, generalized atherosclerosis, or adhesion molecule function., Conclusions: This is the first study allowing direct assessment of BMC homing to the postischemic myocardium. Heterotopic heart transplantation and IVM are proper means to study the myocardial sequestration of BMCs after direct antegrade intracoronary injection in vivo. We show for the first time that intracoronarily injected BMCs sequester exclusively in nutritive myocardial capillaries., (© 2012 John Wiley & Sons Ltd.)

Context: Theory and simulation suggest that randomized controlled trials (RCTs) stopped early for benefit (truncated RCTs) systematically overestimate treatment effects for the outcome that precipitated early stopping., Objective: To compare the treatment effect from truncated RCTs with that from meta-analyses of RCTs addressing the same question but not stopped early (nontruncated RCTs) and to explore factors associated with overestimates of effect., Data Sources: Search of MEDLINE, EMBASE, Current Contents, and full-text journal content databases to identify truncated RCTs up to January 2007; search of MEDLINE, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects to identify systematic reviews from which individual RCTs were extracted up to January 2008., Study Selection: Selected studies were RCTs reported as having stopped early for benefit and matching nontruncated RCTs from systematic reviews. Independent reviewers with medical content expertise, working blinded to trial results, judged the eligibility of the nontruncated RCTs based on their similarity to the truncated RCTs., Data Extraction: Reviewers with methodological expertise conducted data extraction independently., Results: The analysis included 91 truncated RCTs asking 63 different questions and 424 matching nontruncated RCTs. The pooled ratio of relative risks in truncated RCTs vs matching nontruncated RCTs was 0.71 (95% confidence interval, 0.65-0.77). This difference was independent of the presence of a statistical stopping rule and the methodological quality of the studies as assessed by allocation concealment and blinding. Large differences in treatment effect size between truncated and nontruncated RCTs (ratio of relative risks <0.75) occurred with truncated RCTs having fewer than 500 events. In 39 of the 63 questions (62%), the pooled effects of the nontruncated RCTs failed to demonstrate significant benefit., Conclusions: Truncated RCTs were associated with greater effect sizes than RCTs not stopped early. This difference was independent of the presence of statistical stopping rules and was greatest in smaller studies.

Background: Randomized clinical trials (RCTs) stopped early for benefit often receive great attention and affect clinical practice, but pose interpretational challenges for clinicians, researchers, and policy makers. Because the decision to stop the trial may arise from catching the treatment effect at a random high, truncated RCTs (tRCTs) may overestimate the true treatment effect. The Study Of Trial Policy Of Interim Truncation (STOPIT-1), which systematically reviewed the epidemiology and reporting quality of tRCTs, found that such trials are becoming more common, but that reporting of stopping rules and decisions were often deficient. Most importantly, treatment effects were often implausibly large and inversely related to the number of the events accrued. The aim of STOPIT-2 is to determine the magnitude and determinants of possible bias introduced by stopping RCTs early for benefit., Methods/design: We will use sensitive strategies to search for systematic reviews addressing the same clinical question as each of the tRCTs identified in STOPIT-1 and in a subsequent literature search. We will check all RCTs included in each systematic review to determine their similarity to the index tRCT in terms of participants, interventions, and outcome definition, and conduct new meta-analyses addressing the outcome that led to early termination of the tRCT. For each pair of tRCT and systematic review of corresponding non-tRCTs we will estimate the ratio of relative risks, and hence estimate the degree of bias. We will use hierarchical multivariable regression to determine the factors associated with the magnitude of this ratio. Factors explored will include the presence and quality of a stopping rule, the methodological quality of the trials, and the number of total events that had occurred at the time of truncation.Finally, we will evaluate whether Bayesian methods using conservative informative priors to "regress to the mean" overoptimistic tRCTs can correct observed biases., Discussion: A better understanding of the extent to which tRCTs exaggerate treatment effects and of the factors associated with the magnitude of this bias can optimize trial design and data monitoring charters, and may aid in the interpretation of the results from trials stopped early for benefit.