Vago-splenic signal transduction of cardioprotection in humans.

BACKGROUND AND AIMS: The spleen serves as an important relay organ that releases cardioprotective factor(s) upon vagal activation during remote ischaemic conditioning (RIC) in rats and pigs. The translation of these findings to humans was attempted. METHODS: Remote ischaemic conditioning or electrical auricular tragus stimulation (ATS) were performed in 10 healthy young volunteers, 10 volunteers with splenectomy, and 20 matched controls. Venous blood samples were taken before and after RIC/ATS or placebo, and a plasma dialysate was infused into isolated perfused rat hearts subjected to global ischaemia/reperfusion. RESULTS: Neither left nor right RIC or ATS altered heart rate and heart rate variability in the study cohorts. With the plasma dialysate prepared before RIC or ATS, respectively, infarct size (% ventricular mass) in the recipient rat heart was 36 ± 6% (left RIC), 34 ± 3% (right RIC) or 31 ± 5% (left ATS), 35 ± 5% (right ATS), and decreased with the plasma dialysate from healthy volunteers after RIC or ATS to 20 ± 4% (left RIC), 23 ± 6% (right RIC) or to 19 ± 4% (left ATS), 26 ± 9% (right ATS); infarct size was still reduced with plasma dialysate 4 days after ATS and 9 days after RIC. In a subgroup of six healthy volunteers, such infarct size reduction was abrogated by intravenous atropine. Infarct size reduction by RIC or ATS was also abrogated in 10 volunteers with splenectomy, but not in their 20 matched controls. CONCLUSIONS: In humans, vagal innervation and the spleen as a relay organ are decisive for the cardioprotective signal transduction of RIC and ATS.

Perspective on statistical power and equivalence tests.

The use of both sexes or genders should be considered in experimental design, analysis, and reporting. Since there is no requirement to double the sample size or to have sufficient power to study sex differences, challenges for the statistical analysis can arise. In this article, we focus on the topics of statistical power and ways to increase this power. We also discuss the choice of an appropriate design and statistical method and include a separate section on equivalence tests needed to show the absence of a relevant difference.

"Expression of concern": publication bias for positive preclinical cardioprotection studies.

The present analysis reports on the robustness of preclinical cardioprotection studies with infarct size as endpoint which were published in Basic Research in Cardiology, Cardiovascular Research, and Circulation Research between January 2013 and December 2023. Only 26 out of 269 papers with technically robust analysis of infarct size by triphenyltetrazolium chloride staining, magnetic resonance imaging or single photon emission tomography applied a prospective power analysis. A retrospective power calculation revealed that only 75% of the reported data sets with statistically significant positive results from all these studies had a statistical power of ≥ 0.9, and an additional 9% had a statistical power ≥ 0.8. The remaining 16% of all significant positive data sets did not even reach the 0.8 threshold. Only 13% of all analyzed data sets were neutral. We conclude that neutral studies are underreported and there is indeed a significant lack of robustness in many of the published preclinical cardioprotection studies which may contribute to the difficulties of translating cardioprotection to patient benefit.

Underestimation of Pearson's product moment correlation statistic.

Pearson's product moment correlation coefficient (more commonly Pearson's r) tends to underestimate correlations that exist in the underlying population. This phenomenon is generally unappreciated in studies of ecology, although a range of corrections are suggested in the statistical literature. The use of Pearson's r as the classical measure for correlation is widespread in ecology, where manipulative experiments are impractical across the large spatial scales concerned; it is therefore vital that ecologists are able to use this correlation measure as effectively as possible. Here, our literature review suggests that corrections for the issue of underestimation in Pearson's r should not be adopted if either the data deviate from bivariate normality or sample size is greater than around 30. Through our simulations, we then aim to offer advice to researchers in ecology on situations where both distributions can be described as normal, but sample sizes are lower than around 30. We found that none of the methods currently offered in the literature to correct the underestimation bias offer consistently reliable performance, and so we do not recommend that they be implemented when making inferences about the behaviour of a population from a sample. We also suggest that, when considering the importance of the bias towards underestimation in Pearson's product moment correlation coefficient for biological conclusions, the likely extent of the bias should be discussed. Unless sample size is very small, the issue of sample bias is unlikely to call for substantial modification of study conclusions.

Impact of electrical defibrillation on infarct size and no-reflow in pigs subjected to myocardial ischemia-reperfusion without and with ischemic conditioning.

Ventricular fibrillation (VF) occurs frequently during myocardial ischemia-reperfusion (I/R) and must then be terminated by electrical defibrillation. We have investigated the impact of VF/defibrillation on infarct size (IS) or area of no reflow (NR) without and with ischemic conditioning interventions. Anesthetized pigs were subjected to 60/180 min of coronary occlusion/reperfusion. VF, as identified from the ECG, was terminated by intrathoracic defibrillation. The area at risk (AAR), IS, and NR were determined by staining techniques (patent blue, triphenyltetrazolium chloride, and thioflavin-S). Four experimental protocols were analyzed: I/R (n = 49), I/R with ischemic preconditioning (IPC; n = 22), I/R with ischemic postconditioning (POCO; n = 22), or I/R with remote IPC (RIPC; n = 34). The incidence of VF was not different between I/R (44%), IPC (45%), POCO (50%), and RIPC (33%). IS was reduced by IPC (23 ± 12% of AAR), POCO (31 ± 16%), and RIPC (22 ± 13%, all P < 0.05 vs. I/R: 41 ± 12%). NR was not different between protocols (I/R: 17 ± 15% of AAR, IPC: 15 ± 18%, POCO: 25 ± 16%, and RIPC: 18 ± 17%). In pigs with defibrillation, IS was 50% larger than in pigs without defibrillation but independent of the number of defibrillations. Analysis of covariance confirmed the established determinants of IS, i.e., AAR, residual blood flow during ischemia (RMBFi), and a conditioning protocol, and revealed VF/defibrillation as a novel covariate. VF/defibrillation in turn was associated with larger AAR and lower RMBFi. Lack of dose-response relation between IS and the number of defibrillations excluded direct electrical injury as the cause of increased IS. Obviously, AAR size and RMBFi account for both IS and the incidence of VF. IS and NR are mechanistically distinct phenomena.NEW & NOTEWORTHY Ventricular fibrillation/defibrillation is associated with increased infarct size. Electrical injury is unlikely the cause of such association, since there is no dose-response relation between infarct size and number of defibrillations. Ventricular fibrillation, in turn, is associated with a larger area at risk and lower residual blood flow.

Confounders of Cardioprotection by Remote Ischemic Preconditioning in Patients Undergoing Coronary Artery Bypass Grafting.

OBJECTIVES: Remote ischemic conditioning (RIC) by repetitive blood pressure cuff inflation/deflation around a limb provides cardioprotection in patients undergoing coronary artery bypass grafting (CABG). Cardioprotection is confounded by risk factors, comorbidities and comedications. We aimed to identify confounders that possibly attenuate the protection provided by RIC. METHODS: In a retrospective analysis of our single-center, randomized, double-blind trial of patients undergoing elective CABG with/without RIC prior to ischemic cardioplegic arrest, we analyzed demographics, medications and intraoperative variables. The primary end point was myocardial injury, as reflected by the area under the curve for serum troponin I (TnI) from baseline to 72 h after surgery. RESULTS: In models with 2 independent variables and in the multivariate analysis, age and aortic cross-clamp time impacted on TnI release. Subgroup analyses confirmed RIC-induced protection in all age tertiles. There was no protection with an aortic cross-clamp time ≤56 min (RIC/control = 1.026 not significant), but there was protection with 57-75 min (RIC/control = 0.757; p = 0.0348) and ≥76 min (RIC/control = 0.735; p = 0.0277). Gender, ß-blockers, statins, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and intraoperative nitroglycerine did not impact on TnI release. CONCLUSION: Age, gender, ß-blockers, statins, ACE inhibitors, ARBs and intraoperative nitroglycerine have no significant impact on RIC-induced cardioprotection during CABG. However, greater myocardial ischemia/reperfusion injury at longer cross-clamp time facilitates the detection of protection by RIC.

Heart rate reduction and longevity in mice.

Heart rate correlates inversely with life span across all species, including humans. In patients with cardiovascular disease, higher heart rate is associated with increased mortality, and such patients benefit from pharmacological heart rate reduction. However, cause-and-effect relationships between heart rate and longevity, notably in healthy individuals, are not established. We therefore prospectively studied the effects of a life-long pharmacological heart rate reduction on longevity in mice. We hypothesized, that the total number of cardiac cycles is constant, and that a 15% heart rate reduction might translate into a 15% increase in life span. C57BL6/J mice received either placebo or ivabradine at a dose of 50 mg/kg/day in drinking water from 12 weeks to death. Heart rate and body weight were monitored. Autopsy was performed on all non-autolytic cadavers, and parenchymal organs were evaluated macroscopically. Ivabradine reduced heart rate by 14% (median, interquartile range 12-15%) throughout life, and median life span was increased by 6.2% (p = 0.01). Body weight and macroscopic findings were not different between placebo and ivabradine. Life span was not increased to the same extent as heart rate was reduced, but nevertheless significantly prolonged by 6.2%.

On the variety of methods for calculating confidence intervals by bootstrapping.

Researchers often want to place a confidence interval around estimated parameter values calculated from a sample. This is commonly implemented by bootstrapping. There are several different frequently used bootstrapping methods for this purpose. Here we demonstrate that authors of recent papers frequently do not specify the method they have used and that different methods can produce markedly different confidence intervals for the same sample and parameter estimate. We encourage authors to be more explicit about the method they use (and number of bootstrap resamples used). We recommend the bias corrected and accelerated method as giving generally good performance; although researchers should be warned that coverage of bootstrap confidence intervals is characteristically less than the specified nominal level, and confidence interval evaluation by any method can be unreliable for small samples in some situations.

Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial.

BACKGROUND: Remote ischaemic preconditioning has been associated with reduced risk of myocardial injury after coronary artery bypass graft (CABG) surgery. We investigated the safety and efficacy of this procedure. METHODS: Eligible patients were those scheduled to undergo elective isolated first-time CABG surgery under cold crystalloid cardioplegia and cardiopulmonary bypass at the West-German Heart Centre, Essen, Germany, between April, 2008, and October, 2012. Patients were prospectively randomised to receive remote ischaemic preconditioning (three cycles of 5 min ischaemia and 5 min reperfusion in the left upper arm after induction of anaesthesia) or no ischaemic preconditioning (control). The primary endpoint was myocardial injury, as reflected by the geometric mean area under the curve (AUC) for perioperative concentrations of cardiac troponin I (cTnI) in serum in the first 72 h after CABG. Mortality was the main safety endpoint. Analysis was done in intention-to-treat and per-protocol populations. This trial is registered with ClinicalTrials.gov, number NCT01406678. FINDINGS: 329 patients were enrolled. Baseline characteristics and perioperative data did not differ between groups. cTnI AUC was 266 ng/mL over 72 h (95% CI 237-298) in the remote ischaemic preconditioning group and 321 ng/mL (287-360) in the control group. In the intention-to-treat population, the ratio of remote ischaemic preconditioning to control for cTnI AUC was 0·83 (95% CI 0·70-0·97, p=0·022). cTnI release remained lower in the per-protocol analysis (0·79, 0·66-0·94, p=0·001). All-cause mortality was assessed over 1·54 (SD 1·22) years and was lower with remote ischaemic preconditioning than without (ratio 0·27, 95% CI 0·08-0·98, p=0·046). INTERPRETATION: Remote ischaemic preconditioning provided perioperative myocardial protection and improved the prognosis of patients undergoing elective CABG surgery. FUNDING: German Research Foundation.

Estimation of the treatment effect in the presence of non-compliance and missing data.

Treatment non-compliance and missing data are common problems in clinical trials. Non-compliance is a broad term including any kind of deviation from the assigned treatment protocol, such as dose modification, treatment discontinuation or switch, often resulting in missing values. Missing values and treatment non-compliance may bias study results. Follow-up of all patients until the planned end of treatment period irrespective of their protocol adherence may provide useful information on the effectiveness of a study drug, taking the actual compliance into account. In this paper, we consider non-compliance as discontinuation of treatment and assume that the endpoint of interest is recorded for some non-complying patients after treatment discontinuation. As a result, the patient's longitudinal profile is dividable into on- and off-treatment observations. Within the framework of depression trials, which usually show a considerably high amount of dropouts, we compare different analysis strategies including both on- and off-treatment observations to gain insight into how the additional use of off-treatment data may affect the trial's outcome. We compare naïve strategies, which simply ignore off-treatment data or treat on- and off-treatment data in the same way, with more complex strategies based on piecewise linear mixed models, which assume different treatment effects for on- and off-treatment data. We show that naïve strategies may considerably overestimate treatment effects. Therefore, it is worthwhile to follow up as many patients as possible until the end of their planned treatment period irrespective of compliance, including all available data in an analysis that accounts for the different treatment conditions.

A new location-scale test based on a combination of the ideas of Levene and Lepage.

Lepage's test combines the Wilcoxon rank-sum and the Ansari-Bradley statistics. We propose to replace the latter statistic by a Wilcoxon rank-sum calculated after Levene's transformation. We use the medians for this transformation, i.e. absolute deviations from sample medians are calculated. The new location-scale test can be carried out as a permutation test based on permutations of the original observations, the Levene transformation has to be applied for each permutation in an intermediate step to calculate the test statistic. Simulations indicate that the new test can be more powerful than an O'Brien-type test and Lepage's test, the latter is the standard nonparametric location-scale test. The new test is illustrated using real data about colony sizes of yellow-eyed penguins and an SAS program to perform the test is freely available.

Turn alternation and the influence of environmental factors on search routes through branched structures by ladybirds (Coccinella septempunctata and Adalia bipunctata).

Turn alternation is a locomotory behaviour wherein an animal makes consecutive turns in opposite directions (left-then-right or right-then-left). It has been suggested that its adaptive function is to maintain locomotion in a relatively constant general direction while negotiating obstacles. Previous work has focussed on the use of turn alternation in prey species in artificial horizontal mazes. In the first study presented here, we tested whether predatory seven-spot ladybirds (Coccinella septempunctata) exhibit turn alternation when repeatedly presented with consecutive choice turning decisions on vertically oriented twigs. Our findings suggest that turn alternation occurs vertically as well as horizontally, on plant structures as well as terrestrially, and in a type of animal (predatory insect) in which turn alternation has received little attention. In the second study presented here, we tested whether characteristics of branched structures explored by two-spot ladybirds (Adalia bipunctata) influence turning decisions. Our findings suggest that ladybirds exhibit preferences for thicker over thinner, straighter over more deviating headings, and higher over lower turning choice options at bifurcations. These exploratory studies indicate that while turn alternation is an observable phenomenon in ladybirds, it is not the only predictor of searching behaviour on branched structures.

Coronary Artery Bypass Graft Surgery in Patients With Acute Coronary Syndromes After Primary Percutaneous Coronary Intervention: A Current Report From the North-Rhine Westphalia Surgical Myocardial Infarction Registry.

Background Coronary artery bypass grafting has remained an important treatment option for acute coronary syndromes, particularly in patients (1) with ongoing ischemia and large areas of jeopardized myocardium, if percutaneous coronary intervention (PCI) cannot be performed; (2) following successful PCI of the culprit lesion with further indication for coronary artery bypass grafting; and (3) where PCI is incomplete, not sufficient, or failed. Methods and Results We aimed to analyze coronary artery bypass grafting outcome following prior PCI in acute coronary syndromes from the North-Rhine-Westphalia surgical myocardial infarction registry comprising 2616 patients. Primary end points were in-hospital all-cause mortality and major adverse cardio-cerebral event. Patients were 68±11 years of age, had 3-vessel and left main-stem disease in 80.4% and 45.3%, presenting a logistic EuroSCORE of 15.1% in unstable angina, 20.3% in non-ST-segment-elevation myocardial infarction, and 23.5% in ST-segment-elevation myocardial infarction. A history of PCI was present in 36.2% and PCI was performed within 24 hours before surgery in 5.2% in unstable angina, 5.9% in non-ST-segment-elevation myocardial infarction, and 16.1% in ST-segment-elevation myocardial infarction. PCI failed in 5.3% in unstable angina, 6.8% in non-ST-segment-elevation myocardial infarction and 17.2% in ST-segment-elevation myocardial infarction, and 28.8% of patients presented with cardiogenic shock. In-hospital mortality without PCI was 7.4%, but increased to 8.7% with prior PCI >24 hours, 14.5% with prior PCI <24 hours, and 14.1% with failed PCI (P<0.003). The in-hospital major adverse cardio-cerebral event rate was 16.4% without PCI, but 17.4% with prior PCI >24 hours, 25.6% with prior PCI <24 hours, and 41.3% with failed PCI (P=0.014). Multivariable logistic regression analysis showed prior PCI (P=0.039), as well as failed PCI (P=0.001) to be predictors for in-hospital all-cause mortality and major adverse cardio-cerebral event. Conclusions In the current PCI era, immediately prior or failed PCI before coronary artery bypass grafting in acute coronary syndromes is associated with high perioperative risk, cardiogenic shock, and increased morbidity and mortality.

Intraoperative Hemoadsorption in Patients With Native Mitral Valve Infective Endocarditis.

BACKGROUND: Cardiac surgery in patients with infective endocarditis is associated with high mortality owing to postoperative septic multiorgan failure. Hemoadsorption therapy may improve surgical outcomes by reducing the circulating cytokines. We aimed to evaluate the clinical effects of intraoperative hemoadsorption in patients with mitral valve endocarditis. METHODS: Eligible candidates were patients with infective endocarditis of the native mitral valve undergoing cardiac surgery between January 2014 and July 2018. Patients with intraoperative hemoadsorption (hemoadsorption) were compared with surgery without hemoadsorption (control). The end points were the incidence of postoperative sepsis, sepsis-associated death, and 30-day mortality. Furthermore, postoperative need for epinephrine and norepinephrine and systemic vascular resistance were evaluated. RESULTS: A total of 58 consecutive patients were included: 30 in the hemoadsorption group and 28 in the control group. Postoperative sepsis occurred in 5 patients in the hemoadsorption group and in 11 in the control group (P = .05). No sepsis-associated death occurred in the hemoadsorption group, whereas five septic patients in the control group died (P = .02). Thirty-day mortality was 10% in the hemoadsorption group versus 18% in the control group (P = .39). On intensive care unit admission, the cumulative need for epinephrine and norepinephrine was 0.15 versus 0.24 µg/kg body weight/min (P = .01) and the median systemic vascular resistance was 1413 versus 1010 dyn·s·cm-5 (P = .02) in the hemoadsorption versus control group, respectively. CONCLUSIONS: Intraoperative hemoadsorption might reduce the incidence of postoperative sepsis and sepsis-related death. In addition, patients with intraoperative hemoadsorption showed greater hemodynamic stability. These data suggest that intraoperative hemoadsorption may improve surgical outcome in patients with mitral valve endocarditis.

Surgical revascularization for acute coronary syndromes: a report from the North Rhine-Westphalia surgical myocardial infarction registry.

OBJECTIVES: The aim of this was to analyse current outcomes in patients referred to coronary artery bypass grafting (CABG) for acute coronary syndromes (ACSs), including ST-elevation or non-ST-elevation ACS (non-ST-segment elevation myocardial infarction) or unstable angina. METHODS: Patients (n = 2432) undergoing CABG for ACS between January 2010 and December 2017 were prospectively entered into a surgical myocardial infarction registry in North Rhine-Westphalia, Germany. Key end points were in-hospital all-cause mortality (IHM) and major adverse cardio-cerebral events (MACCE). Predictors for IHM and MACCE were analysed by multivariable logistic regression. RESULTS: Patients (78% males) were referred for CABG for unstable angina (25%), non-ST-segment elevation myocardial infarction (50%), and ST-segment elevation myocardial infarction (25%). The mean patient age was 68 ± 11 years, logistic EuroSCORE was 19 ± 18% and three-vessel and left main stem diseases were diagnosed in 81% and 45% of patients, respectively. On-pump CABG with cardiac arrest or beating heart was performed in 92% and 2%, respectively, with only 6% off-pump surgery and 6% multiple arterial revascularization (3.1 ± 1.0 grafts, 93% left internal thoracic artery). Emergency CABG was performed in 23% of patients (42% in ST-segment elevation myocardial infarction; P < 0.001). The total IHM and MACCE rates were 8.1% and 17.5% and were highest in ST-segment elevation myocardial infarction patients with 12.6% and 28.5%, respectively (P < 0.001). Key predictors for IHM and MACCE were female gender, elevated troponin, left ventricular ejection fraction, inotropic support, logistic EuroSCORE, cardiopulmonary bypass and aortic clamp time and the need for emergency CABG. CONCLUSIONS: Surgical myocardial revascularization in patients with ACS is still linked to substantial in-hospital mortality. Emergency CABG for patients with ACS was associated with poorer outcomes.

Extra-pair young in house wren broods are more likely to be male than female.

Sex-allocation theory predicts that females should preferentially produce offspring of the sex with greater fitness potential. In socially monogamous animal species, extra-pair mating often increases the variance in fitness of sons relative to daughters. Thus, in situations where offspring sired by a female's extra-pair mate(s) will typically have greater fitness potential than offspring sired by the within-pair mate, sex-allocation theory predicts that females will bias the sex of offspring sired by extra-pair mates towards male. We examined the relationship between offspring sex and paternity over six breeding seasons in an Illinois population of the house wren (Troglodytes aedon), a cavity-nesting songbird. Out of the 2345 nestlings that had both sex and paternity assigned, 350 (15%) were sired by extra-pair males. The sex ratio of extra-pair offspring, 0.534, was significantly greater than the sex ratio of within-pair offspring, 0.492, representing an increase of 8.5 per cent in the proportion of sons produced. To our knowledge, this is the first confirmed report of female birds increasing their production of sons in association with extra-pair fertilization. Our results are consistent with the oft-mentioned hypothesis that females engage in extra-pair mating to increase offspring quality.

Results of a propensity score-matched comparison of the Perimount Magna and Mosaic Ultra aortic valve prostheses.

BACKGROUND AND AIM OF THE STUDY: Hemodynamic function and clinical outcomes were compared between the bovine pericardial Edwards Perimount Magna (EPM) and the porcine Medtronic Mosaic Ultra (MMU) aortic valve prostheses. METHODS: Between January 2003 and June 2007, a total of 227 consecutive patients was prospectively enrolled, and received either the EPM (n = 125) or the MMU (n = 102) aortic valve prosthesis. The primary study end-point was the mean transvalvular gradient after surgery, at discharge and at six months follow up, as measured echocardiographically. The secondary study end-points were 30-day mortality and major adverse cardiac events (MACEs). RESULTS: The intraoperative transvalvular mean pressure gradients were 9.4 +/- 4.6 mmHg in the EPM group compared to 17.7 +/- 6.7 mmHg in the MMU group (p < 0.001), and these remained essentially unchanged at hospital discharge (11.2 +/- 4.2 mmHg versus 19.1 +/- 6 mmHg; p < 0.001) and at six months' follow up (10 +/- 5 mmHg versus 20 +/- 7 mmHg; p < 0.001). A multivariable risk-adjusted analysis of covariance revealed the MMU valve (p < 0.0001) to be strongly associated with elevated postoperative mean transvalvular gradients during the six-month follow up. In addition, renal insufficiency, concomitant valve surgery and reoperation were identified as being significantly associated with in-hospital mortality (OR 3.3, 95% CI 1.3-8.1; OR 3.7, 95% CI 1.4-9.8; OR 3.3, 95% CI 1.1-10.2, respectively) and major adverse cardiac events (OR 2.2, 95% CI 1.0-4.7; OR 3.7, 95% CI 1.7-8.2; OR 2.7, 95% CI 1.1-7.2, respectively). To further control for selection bias, the propensity score was computed based on the major risk factors of 12 patients. An analysis of covariance model, adjusted for the propensity score, also confirmed the MMU prosthesis to be strongly associated with elevated mean transvalvular gradients during the six-month follow up period (p < 0.0001). CONCLUSION: The study results clearly demonstrated a favorable hemodynamic function as shown by lower transvalvular gradients of the bovine pericardial Edwards Perimount Magna compared to the porcine Medtronic Mosaic Ultra aortic valve prosthesis.

R0 liver resections for primary malignant liver tumors in the noncirrhotic liver: a diagnosis-related analysis.

BACKGROUND: Primary liver cancer constitutes an increasingly malignancy in the Western world and one of the leading causes of cancer-related deaths worldwide. The purpose of this study was to evaluate and compare long-term outcomes after R0 resections in noncirrhotic livers for hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). METHODS: Between April 1998 and May 2006 a total of 102 patients with either ICC (n = 41, group 1) or HCC (n = 61, group 2) in the absence of cirrhosis underwent curative liver resection in our department. Demographic characteristics, operative details, perioperative complications, pathologic findings, tumor recurrence and survival were analyzed. RESULTS: Gender (P = 0.007), extent of liver resection (P = 0.036), additional surgical procedures (P < 0.001) and operative morbidity (P = 0.018) differed among the two groups. Following resection, after a median follow-up of 28 months, the calculated 5-year survival was 44% and 40% for ICC and HCC, respectively (P = 0.38). The corresponding recurrence-free survival was 25% for both ICC and HCC (P = 0.66). UICC stage was found to predict overall and recurrence-free survival in both types of tumors. Multifocality in the case of ICC, and tumor differentiation and vascular invasion in the case of HCC, were predictive factors for overall and recurrence-free survival, respectively. In multivariable analyses, vascular invasion for HCC was predictive for overall and recurrence-free survival, whereas in the case of ICC significant differences were detected in the recurrence analysis for multifocality and UICC stage. CONCLUSIONS: R0 resections for both ICC and HCC result to similar long-term outcomes, which are characterized by good overall and acceptable recurrence-free survival rates.

Early Clinical Outcomes of Surgical Myocardial Revascularization for Acute Coronary Syndromes Complicated by Cardiogenic Shock: A Report From the North-Rhine-Westphalia Surgical Myocardial Infarction Registry.

Background Coronary artery bypass grafting for acute coronary syndrome complicated by cardiogenic shock ( CS ) is associated with a high mortality. This registry study aimed to distinguish between early surgical outcomes of CS patients with non- ST -segment-elevation myocardial infarction ( NSTEMI ) and ST -segment-elevation myocardial infarction ( STEMI ). Methods and Results Patients with NSTEMI (n=1218) or STEMI (n=618) referred for coronary artery bypass grafting were enrolled in a prospective multicenter registry between 2010 and 2017. CS was present in 227 NSTEMI (18.6%) and 243 STEMI patients (39.3%). Key clinical end points were in-hospital mortality ( IHM ) and major adverse cardiocerebral events ( MACCEs ). Predictors for IHM and MACCEs were identified using multivariable logistic regression analysis. STEMI patients with CS were younger, had a lower prevalence of diabetes mellitus and multivessel disease, and exhibited higher myocardial injury (troponin 9±17 versus 3±6 ng/mL) before surgery compared with patients with NSTEMI ( P<0.05). Emergency coronary artery bypass grafting was performed more often in STEMI (58%) versus NSTEMI (40%; P=0.002). On-pump surgery with cardioplegia was the preferred surgical technique in CS . IHM and MACCE rates were 24% and 49% in STEMI patients with CS and were higher compared with NSTEMI ( IHM 15% versus MACCE 34%; P<0.001). Predictors for IHM and MACCE in CS were a reduced ejection fraction and a higher European System for Cardiac Operative Risk Evaluation score. Conclusions Surgical revascularization in NSTEMI and STEMI patients with CS is associated with a substantial but not prohibitive IHM and MACCE rate. Worse early outcomes were found for patients with STEMI complicated by CS compared with NSTEMI patients.