Circulating Tumor Cells as a Prognostic Factor in Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma: The CIRCUTEC Prospective Study.

BACKGROUND: This prospective multicenter study evaluated the prognostic value of circulating tumor cells (CTCs) in relapsing nonoperable or metastatic head and neck squamous cell carcinoma (rHNSCC) treated by chemotherapy and cetuximab. METHODS: In 65 patients suitable for analyses, peripheral blood was taken at day 0 (D0) D7, and D21 of treatment for CTC detection by CellSearch®, EPISPOT, and flow cytometry (FCM). Progression-free survival (PFS) was assessed with the Kaplan-Meier method and compared with the log-rank test (P < 0.05). RESULTS: At D0, CTCs were detected with EPISPOT, CellSearch, and FCM in 69% (45/65), 21% (12/58), and 11% (7/61) of patients, respectively. In the patients tested with all 3 methods, EPISPOT identified 92% (36/39), 92% (35/38), and 90% (25/28) of all positive samples at D0, D7, and D21, respectively. Median PFS time was significantly lower in (a) patients with increasing or stable CTC counts (36/54) from D0 to D7 with EPISPOTEGFR (3.9 vs 6.2 months; 95% CI, 5.0-6.9; P = 0.0103) and (b) patients with ≥1 CTC detected with EPISPOT or CellSearch® (37/51) (P = 0.0311), EPISPOT or FCM (38/54) (P = 0.0480), and CellSearch or FCM (11/51) (P = 0.0005) at D7. CONCLUSIONS: CTCs can be detected before and during chemotherapy in patients with rHNSCC. D0-D7 CTC kinetics evaluated with EPISPOTEGFR are associated with the response to treatment. This study indicates that CTCs can be used as a real-time liquid biopsy to monitor the early response to chemotherapy in rHNSCC. CLINICALTRIALSGOV IDENTIFIER: NCT02119559.

Randomized controlled trials: significant results-fragile, though.

In their systematic review, Shochet et al. question the robustness of the statistical significance of the results of randomized controlled trials (RCTs) in nephrology reported in high-impact journals (2005-2014). They hypothesized that a high proportion of RCTs in nephrology would be fragile. They calculated a Fragility Index that is a tool for testing robustness of RCTs, based on 107 RCT reports. The observation of an alarming median Fragility Index equal to 3 suggests that in half of the trials, the sole additional occurrence of 3 events would compromise the significance of nominally significant results.

Impact of acute-on-chronic liver failure on 90-day mortality following a first liver transplantation.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is associated with a significant short-term mortality rate (23%-74%), depending on the number of organ failures. Some patients present with ACLF at the time of liver transplantation (LT). The aim of this study was to assess whether ACLF was also a prognostic factor after LT and, if applicable, to construct a score that could predict 90-day mortality. METHODS: Three hundred and fifty cirrhotic patients, who underwent LT between January 2008 and December 2013, were enrolled. We used ACLF grades according to EASL-CLIF consortium criteria to categorize the cirrhotic patients. A propensity score was applied with an Inverse Probability Treatment Weighting in a Cox model. A predictive score of early mortality after LT was generated. RESULTS: One hundred and forty patients (40%) met the criteria for ACLF. The overall mortality rate at 90 days post-transplant was 10.6% (37/350 patients). ACLF at the time of LT (HR: 5.78 [3.42-9.77], P<.001) was an independent predictor of 90-day mortality. Infection occurring during the month before LT, high recipient age and male recipient, the reason for LT and a female donor were also independent risk factors for early mortality. Using these factors, we have proposed a model to predict 90-day mortality after LT. CONCLUSIONS: LT is feasible in cirrhotic patients with ACLF. However, we have shown that ACLF is a significant and independent predictor of 90-day mortality. We propose a score that can identify candidate cirrhotic patients in whom LT might be associated with futile LT.

External validation of the Donor Risk Index and the Eurotransplant Donor Risk Index on the French liver transplantation registry.

BACKGROUND & AIMS: A major limitation to liver transplantation is organ shortage leading to the use of non-optimal liver grafts. The Donor Risk Index has been validated and recommended to select donors/organs. The Eurotransplant Donor Risk Index was derived from the Donor Risk Index. The objective of our study was to perform an external validation of both Donor Risk Index and Eurotransplant-Donor Risk Index against the French liver transplantation Cristal registry according to recommendations of the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis. METHODS: Liver transplantations performed in France between 2009 and 2013 were used to perform the validation study for the Donor Risk Index and the Eurotransplant-Donor Risk Index respectively. We applied on the French data the models used to construct the Donor Risk Index and the Eurotransplant-Donor Risk Index respectively. RESULTS: Neither the Donor Risk Index nor the Eurotransplant-Donor Risk Index were validated against this dataset. Discrimination and calibration of these scores were not preserved according to our data. Important donor and candidates differences between our dataset and the Organ Procurement and Transplantation Network or the Eurotransplant datasets may explain why the Donor Risk Index and the Eurotransplant-Donor Risk Index appeared unadapted to the French transplant registry. CONCLUSION: Neither of these risk indexes were suitable to optimize the French liver allocation system. Thus, our next step will be to propose a general adaptive model for a Donor Risk Index.

On the censored cost-effectiveness analysis using copula information.

BACKGROUND: Information and theory beyond copula concepts are essential to understand the dependence relationship between several marginal covariates distributions. In a therapeutic trial data scheme, most of the time, censoring occurs. That could lead to a biased interpretation of the dependence relationship between marginal distributions. Furthermore, it could result in a biased inference of the joint probability distribution function. A particular case is the cost-effectiveness analysis (CEA), which has shown its utility in many medico-economic studies and where censoring often occurs. METHODS: This paper discusses a copula-based modeling of the joint density and an estimation method of the costs, and quality adjusted life years (QALY) in a cost-effectiveness analysis in case of censoring. This method is not based on any linearity assumption on the inferred variables, but on a punctual estimation obtained from the marginal distributions together with their dependence link. RESULTS: Our results show that the proposed methodology keeps only the bias resulting statistical inference and don't have anymore a bias based on a unverified linearity assumption. An acupuncture study for chronic headache in primary care was used to show the applicability of the method and the obtained ICER keeps in the confidence interval of the standard regression methodology. CONCLUSION: For the cost-effectiveness literature, such a technique without any linearity assumption is a progress since it does not need the specification of a global linear regression model. Hence, the estimation of the a marginal distributions for each therapeutic arm, the concordance measures between these populations and the right copulas families is now sufficient to process to the whole CEA.

Double-adjustment in propensity score matching analysis: choosing a threshold for considering residual imbalance.

BACKGROUND: Double-adjustment can be used to remove confounding if imbalance exists after propensity score (PS) matching. However, it is not always possible to include all covariates in adjustment. We aimed to find the optimal imbalance threshold for entering covariates into regression. METHODS: We conducted a series of Monte Carlo simulations on virtual populations of 5,000 subjects. We performed PS 1:1 nearest-neighbor matching on each sample. We calculated standardized mean differences across groups to detect any remaining imbalance in the matched samples. We examined 25 thresholds (from 0.01 to 0.25, stepwise 0.01) for considering residual imbalance. The treatment effect was estimated using logistic regression that contained only those covariates considered to be unbalanced by these thresholds. RESULTS: We showed that regression adjustment could dramatically remove residual confounding bias when it included all of the covariates with a standardized difference greater than 0.10. The additional benefit was negligible when we also adjusted for covariates with less imbalance. We found that the mean squared error of the estimates was minimized under the same conditions. CONCLUSION: If covariate balance is not achieved, we recommend reiterating PS modeling until standardized differences below 0.10 are achieved on most covariates. In case of remaining imbalance, a double adjustment might be worth considering.

Comparison of the ability of double-robust estimators to correct bias in propensity score matching analysis. A Monte Carlo simulation study.

OBJECTIVE: As covariates are not always adequately balanced after propensity score matching and double- adjustment can be used to remove residual confounding, we compared the performance of several double-robust estimators in different scenarios. METHODS: We conducted a series of Monte Carlo simulations on virtual observational studies. After estimating the propensity scores by logistic regression, we performed 1:1 optimal, nearest-neighbor, and caliper matching. We used 4 estimators on each matched sample: (1) a crude estimator without double-adjustment, (2) double-adjustment for the propensity scores, (3) double-adjustment for the unweighted unbalanced covariates, and (4) double-adjustment for the unbalanced covariates, weighted by their strength of association with the outcome. RESULTS: The crude estimator led to highest bias in all tested scenarios. Double-adjustment for the propensity scores effectively removed confounding only when the propensity score models were correctly specified. Double-adjustment for the unbalanced covariates was more robust to misspecification. Double-adjustment for the weighted unbalanced covariates outperformed the other approaches in every scenario and using any matching algorithm, as measured by the mean squared error. CONCLUSION: Double-adjustment can be used to remove residual confounding after propensity score matching. The unbalanced covariates with the strongest confounding effects should be adjusted.

Preoperative Score to Predict Postoperative Mortality (POSPOM): Derivation and Validation.

BACKGROUND: An accurate risk score able to predict in-hospital mortality in patients undergoing surgery may improve both risk communication and clinical decision making. The aim of the study was to develop and validate a surgical risk score based solely on preoperative information, for predicting in-hospital mortality. METHODS: From January 1, 2010, to December 31, 2010, data related to all surgeries requiring anesthesia were collected from all centers (single hospital or hospitals group) in France performing more than 500 operations in the year on patients aged 18 yr or older (n = 5,507,834). International Statistical Classification of Diseases, 10th revision codes were used to summarize the medical history of patients. From these data, the authors developed a risk score by examining 29 preoperative factors (age, comorbidities, and surgery type) in 2,717,902 patients, and then validated the risk score in a separate cohort of 2,789,932 patients. RESULTS: In the derivation cohort, there were 12,786 in-hospital deaths (0.47%; 95% CI, 0.46 to 0.48%), whereas in the validation cohort there were 14,933 in-hospital deaths (0.54%; 95% CI, 0.53 to 0.55%). Seventeen predictors were identified and included in the PreOperative Score to predict PostOperative Mortality (POSPOM). POSPOM showed good calibration and excellent discrimination for in-hospital mortality, with a c-statistic of 0.944 (95% CI, 0.943 to 0.945) in the development cohort and 0.929 (95% CI, 0.928 to 0.931) in the validation cohort. CONCLUSION: The authors have developed and validated POSPOM, a simple risk score for the prediction of in-hospital mortality in surgical patients.

The impact of emergency department segmentation and nursing staffing increase on inpatient mortality and management times.

BACKGROUND: The aim of our study was to investigate the impact of a new organization of our emergency department (ED) on patients' mortality and management delays. METHODS: The ED segmentation consisted of the development of a new patient care geographical layout on a pre-existing site and changing the organization of patient flow. It took place on May 10, 2012. We did a before-after study in the ED of a university hospital, "before" (winter 2012) and "after" (summer 2012) reorganization by segmentation into sectors. All ED patients were included. RESULTS: Eighty-three thousand three hundred twenty-two patient visits were analyzed, 61,118 in phase "before", 22,204 during the phase "after". The overall inpatient mortality was 1.5 % during summer 2011 ("before" period), 1.8 % during winter 2012 ("before" period), 1.3 % during summer 2012 ("after" period) period (summer 2012 vs. winter 2012, OR = 0.72; 95 % CIs [0.61, 0.85], and summer 2012 vs. summer 2011, OR = 0.85; 95 % CIs [0.72, 0.99]). The mean (SD) time to first medical contact was 129 min (±133) during winter 2012 and 104 min (± 95) during summer 2012 (p < .05). CONCLUSIONS: Our study showed a decrease in mortality and improvement in time to first medical contact after the segmentation of our ED and nursing staffing increase, without an increase in medical personnel. Improving patient care through optimizing ED segmentation may be an effective strategy.

Consequences for overcrowding in the emergency room of a change in bed management policy on available in-hospital beds.

Objective Emergency rooms play an important role by providing continuous access to healthcare 24 h a day, 7 days a week, but the lack of available hospital beds has become a major difficulty. Changing bed management policy could improve patient flow. The aim of the present study was to evaluate the consequences of a change in patient prioritisation on available beds. Methods The study consisted of a computerised bed management simulation based on day-by-day data collected from 1 to 31 January 2013 in a teaching hospital. Real hospital data were used to power the computer simulation. The scenarios tested were: (1) priority for emergency and surgery; (2) priority for emergency and medicine; (3) priority for planned admissions and surgery; and (4) priority for planned admissions and medicine. The results of these scenarios were compared with each other and to actual data. Results This study included 2347 patients. The scenario that proved to be the least efficient was the one that gave priority to emergency patients presenting with a medical condition. The scenario that exhibited the best efficiency was the one that gave priority to planned admissions and surgery. Conclusions Changing policies for hospital bed management is worth exploring to improve hospital patient flow and length of stay. What is known about the topic? The lack of available hospital beds is a major difficulty in managing patient flow in emergency rooms (ERs). The ER patient flow competes against a flow of planned hospital admissions for the same beds and the lack of a clearly defined policy on either prioritising ER patient flow over planned admissions or vice versa contributes to a disordered system. What does this paper add? We compared several simulated scenarios corresponding to different bed management policies. The scenario that gave priority to planned admissions and surgery gave the most suitable results. What are the implications for practitioners? Postponing scheduled surgical patients was not an efficient procedure to solve hospital overcrowding.

Prostate cancer: net survival and cause-specific survival rates after multiple imputation.

BACKGROUND: Estimations of survival rates are diverse and the choice of the appropriate method depends on the context. Given the increasing interest in multiple imputation methods, we explored the interest of a multiple imputation approach in the estimation of cause-specific survival, when a subset of causes of death was observed. METHODS: By using European Randomized Study of Screening for Prostate Cancer (ERSPC), 20 multiply imputed datasets were created and analyzed with a Multivariate Imputation by Chained Equation (MICE) algorithm. Then, cause-specific survival was estimated on each dataset with two methods: Kaplan-Meier and competing risks. The two pooled cause-specific survival and confidence intervals were obtained using Rubin's rules after complementary log-log transformation. Net survival was estimated using Pohar-Perme's estimator and was compared to pooled cause-specific survival. Finally, a sensitivity analysis was performed to test the robustness of our constructed multiple imputation model. RESULTS: Cause-specific survival performed better than net survival, since this latter exceeded 100 % for almost the first 2 years of follow-up and after 9 years whereas the cause-specific survival decreased slowly and than stabilized at around 94 % at 9 years. Sensibility study results were satisfactory. CONCLUSIONS: On our basis of prostate cancer data, the results obtained by cause-specific survival after multiple imputation appeared to be better and more realistic than those obtained using net survival.

Outcomes After Hip Fracture Surgery Compared With Elective Total Hip Replacement.

IMPORTANCE: Patients undergoing surgery for a hip fracture have a higher risk of mortality and major complications compared with patients undergoing an elective total hip replacement (THR) operation. The effect of older age and comorbidities associated with hip fracture on this increased perioperative risk is unknown. OBJECTIVE: To determine if there was a difference in hospital mortality among patients who underwent hip fracture surgery relative to an elective THR, after adjustment for age, sex, and preoperative comorbidities. DESIGN, SETTING, AND PARTICIPANTS: Using the French National Hospital Discharge Database from January 2010 to December 2013, patients older than 45 years undergoing hip surgery at French hospitals were included. The International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10), codes were used to determine patients' comorbidities and complications after surgery. A population matched for age, sex, and preoperative comorbidities of patients who underwent elective THR or hip fracture surgery was created using a multivariable logistic model and a greedy matching algorithm with a 1:1 ratio. EXPOSURE: Hip fracture. MAIN OUTCOMES AND MEASURES: Postoperative in-hospital mortality. RESULTS: A total of 690,995 eligible patients were included from 864 centers in France. Patients undergoing elective THR surgery (n = 371,191) were younger, more commonly men, and had less comorbidity compared with patients undergoing hip fracture surgery. Following hip fracture surgery (n = 319,804), 10,931 patients (3.42%) died before hospital discharge and 669 patients (0.18%) died after elective THR. Multivariable analysis of the matched populations (n = 234,314) demonstrated a higher risk of mortality (1.82% for hip fracture surgery vs 0.31% for elective THR; absolute risk increase, 1.51% [95% CI, 1.46%-1.55%]; relative risk [RR], 5.88 [95% CI, 5.26-6.58]; P < .001) and of major postoperative complications (5.88% for hip fracture surgery vs 2.34% for elective THR; absolute risk increase, 3.54% [95% CI, 3.50%-3.59%]; RR, 2.50 [95% CI, 2.40-2.62]; P < .001) among patients undergoing hip fracture surgery. CONCLUSIONS AND RELEVANCE: In a large cohort of French patients, hip fracture surgery compared with elective THR was associated with a higher risk of in-hospital mortality after adjustment for age, sex, and measured comorbidities. Further studies are needed to define the causes for these differences.

Increased risk of solid renal tumors in lithium-treated patients.

Cystic kidney diseases and toxic interstitial nephritis may be complicated by renal tumors. Long-term lithium intake is associated with tubulointerstitial nephritis and renal cysts but to date such an association with tumors has not been determined. We evaluated this in a retrospective study to determine whether lithium-treated patients were at higher risk of renal tumors compared with lithium-free patients with chronic kidney disease (CKD), and to the general population. Over a 16-year period, 14 of 170 lithium-treated patients had renal tumors, including seven malignant and seven benign tumors. The mean duration of lithium exposure at diagnosis was 21.4 years. The renal cancers included three clear-cell and two papillary renal cell carcinomas, one hybrid tumor with chromophobe and oncocytoma characteristics, and one clear-cell carcinoma with leiomyomatous stroma. The benign tumors included four oncocytomas, one mixed epithelial and stromal tumor, and two angiomyolipomas. The percentage of renal tumors, particularly cancers and oncocytomas, was significantly higher in lithium-treated patients compared with 340 gender-, age-, and estimated glomerular filtration rate (eGFR)-matched lithium-free patients. Additionally, the Standardized Incidence Ratio of renal cancer was significantly higher in lithium-treated patients compared with the general population: 7.51 (95% confidence interval (CI) (1.51-21.95)) and 13.69 (95% CI (3.68-35.06)) in men and women, respectively. Thus, there is an increased risk of renal tumors in lithium-treated patients.

Transplantation in patients with SCID: mismatched related stem cells or unrelated cord blood?

Pediatric patients with SCID constitute medical emergencies. In the absence of an HLA-identical hematopoietic stem cell (HSC) donor, mismatched related-donor transplantation (MMRDT) or unrelated-donor umbilical cord blood transplantation (UCBT) are valuable treatment options. To help transplantation centers choose the best treatment option, we retrospectively compared outcomes after 175 MMRDTs and 74 UCBTs in patients with SCID or Omenn syndrome. Median follow-up time was 83 months and 58 months for UCBT and MMRDT, respectively. Most UCB recipients received a myeloablative conditioning regimen; most MMRDT recipients did not. UCB recipients presented a higher frequency of complete donor chimerism (P = .04) and faster total lymphocyte count recovery (P = .04) without any statistically significance with the preparative regimen they received. The MMRDT and UCBT groups did not differ in terms of T-cell engraftment, CD4(+) and CD3(+) cell recoveries, while Ig replacement therapy was discontinued sooner after UCBT (adjusted P = .02). There was a trend toward a greater incidence of grades II-IV acute GVHD (P = .06) and more chronic GVHD (P = .03) after UCBT. The estimated 5-year overall survival rates were 62% ± 4% after MMRDT and 57% ± 6% after UCBT. For children with SCID and no HLA-identical sibling donor, both UCBT and MMRDT represent available HSC sources for transplantation with quite similar outcomes.

A model combining excess and relative mortality for population-based studies.

Considering expected mortality provides an attractive approach to analyse mortality of population-based cohorts of patients presenting with a chronic disease. Two classes of methods are available: either modelling the excess mortality using an additive hazard model or modelling the relative mortality using a multiplicative hazard model. Because these two models are informative to look for factors associated with mortality related to a chronic disease, we developed an alternative model modelling both the excess and the relative mortality. We generalised Andersen and Vaeth's model to fit covariates and obtain directly an estimation of the Excess Mortality Ratio and Relative Mortality Ratio for each covariate. We assessed the performances of the combined model by using simulations, and it appeared satisfactorily. We illustrate the combined model by data collected in patients presenting with end-stage renal disease and treated by dialysis. The combined model offers the possibility of performing pure additive and multiplicative models and thus to compare their log-likelihoods. The combined model appears useful to select one of these pure models or to conclude to the need of modelling both excess and relative mortality. In this latter case, our model enabled better describing the effect of covariates on the excess and relative mortality.

The long-term impact of early cardiovascular therapy intensification for postoperative troponin elevation after major vascular surgery.

BACKGROUND: Acute cardiac events are a frequent cause of morbidity after vascular surgery. The impact of early evidence-based treatment for patients with an acute cardiac event after vascular surgery on long-term postoperative outcomes has not been extensively studied. We hypothesized that providing appropriate evidence-based treatment to patients with elevated postoperative cardiac troponin levels may limit long-term mortality. METHODS: We conducted a study of 667 consecutive major vascular surgery patients with an elevated postoperative troponin I level. We then determined which of these patients received medical therapy as per the 2007 American College of Cardiology/American Heart Association recommendations for the medical management of patients with chronic stable angina. All patients with troponin elevation were then matched with 2 control patients without postoperative troponin elevation. Matching was done using logistic regression and nearest-neighbor matching methods. The primary study end point was 12 months survival without a major cardiac event (i.e., death, myocardial infarction, coronary revascularization, or pulmonary edema requiring hospitalization). RESULTS: Therapy was intensified in 43 of 66 patients (65%) who suffered a troponin I elevation after surgery. Patients with a troponin I elevation not receiving intensified cardiovascular treatment had a hazard ratio (HR) of 1.77 (95% confidence interval (CI), 1.13-2.42; P = 0.004) for the primary study outcome as compared with the control group. In contrast, patients with a troponin I elevation who received intensified cardiovascular treatment had an HR of 0.63 (95% CI, 0.10-1.19; P = 0.45) for the primary outcome as compared with the control group. Patients with a troponin I elevation not receiving treatment intensification likely were at higher risk for a major cardiac event (HR, 2.80; 95% CI, 1.05-24.2; P = 0.04) compared with patients who did receive treatment intensification. CONCLUSIONS: The main finding of this study was that in patients with elevated troponin I levels after noncardiac surgery, long-term adverse cardiac outcomes may likely be improved by following evidence-based recommendations for the medical management of acute coronary syndromes.

Prescription errors by emergency physicians for inpatients are associated with emergency department length of stay.

OBJECTIVES: Adverse drug events are the sixth-leading cause of death in Western countries and are also more frequent in emergency departments (EDs). In some hospitals or on some occasions, ED physicians prescribe for patients who they have admitted. These prescriptions are then followed by the wards and can persist for several days. Our objectives were to determine the frequency of prescription errors for patients over 18years old hospitalized from ED to medical or surgical wards, and whether there exists a relationship between those prescription errors and ED LOS. METHODS: This was a single center retrospective study that was conduct in the ED of a university hospital with an annual census of 65 000 patients. The population studied consisted of patients over 18years old hospitalized from ED to medical or surgical wards between January 1st, 2012 and January 21st, 2012. RESULTS: Six hundred eight patients were included. One hundred fifty-four (25%) patients had prescription errors. Prescription errors were associated with increased ED length of stay (OR=2.47; 95% CIs [1.58; 3.92]) and polypharmacy (OR=1.78; 95% CIs [1.20; 2.66]). Fewer prescription errors were found when the patient was examined in the ED by a consultant (OR=0.61; 95% CIs [0.41; 0.91]) and when the medical history was known (OR=0.28; 95% CIs [0.10; 0.88]). CONCLUSION: Prescription errors occurred frequently in the ED. We assume that a clear communication and cooperation between EPs and consultants may help improve prescription accuracy.

Impact of perioperative bleeding on the protective effect of ß-blockers during infrarenal aortic reconstruction.

BACKGROUND: The use of ß-blockers during the perioperative period remains controversial. Although some studies have demonstrated their protective effects regarding postoperative cardiac complications, others have demonstrated increased mortality when ß-blockers were introduced before surgery. METHODS: In this observational study involving 1,801 patients undergoing aortic reconstruction, we prospectively assessed ß-blocker therapy compared with no ß-blocker therapy, with regard to cardiac and noncardiac postoperative outcomes using a propensity score approach. The impact of ß-blockers was analyzed according to the intraoperative bleeding estimated by transfusion requirements. RESULTS: In-hospital mortality was 2.5% (n=45), ß-blocker use was associated with a reduced frequency of postoperative myocardial infarction (OR=0.46, 95% CI [0.26; 0.80]) and myocardial necrosis (OR=0.62, 95% CI [0.43; 0.88]) in all patients, but also with an increased frequency of multiple organ dysfunction syndromes (OR=2.78, 95% CI [1.71; 4.61]). In patients with severe bleeding (n=163; 9.1%), the frequency of in-hospital death (OR=6.65, 95% CI [1.09; 129]) and/or multiple organ dysfunction syndromes (OR=4.18, 95% CI [1.81; 10.38]) were markedly increased. Furthermore, no more than 28% of the patients who died presented with postoperative myocardial infarction, whereas 69% of the patient with a postoperative myocardial infarction also presented an excessive bleeding. CONCLUSIONS: Perioperative ß-blocker therapy was associated with an overall reduction in postoperative cardiac events. In the vast majority of patients with low perioperative bleeding, the global effect of ß-blockers was protective; in contrast, patients given ß-blockers who experienced severe bleeding had higher mortality and an increased frequency of multiorgan dysfunction syndrome.