Hybrid PET/MR imaging for the prediction of left ventricular recovery after percutaneous revascularisation of coronary chronic total occlusions.

PURPOSE: To evaluate myocardial viability assessment with hybrid 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/magnetic resonance imaging ([18F]FDG-PET/MR) in predicting left ventricular (LV) wall motion recovery after percutaneous revascularisation of coronary chronic total occlusion (CTO). METHODS AND RESULTS: Forty-nine patients with CTO and corresponding wall motion abnormality (WMA) underwent [18F]FDG-PET/MR imaging for viability assessment prior to percutaneous revascularisation. After 3-6 months, 23 patients underwent follow-up MR to evaluate wall motion recovery. In total, 124 segments were assigned to the CTO territories, while 80 segments displayed impaired wall motion. Of these, 68% (54) were concordantly viable in PET and MR; conversely, only 2 segments (2%) were assessed non-viable by both modalities. However, 30% showed a discordant viability pattern, either PET non-viable/MR viable (3 segments, 4%) or PET viable/MR non-viable (21 segments, 26%), and the latter revealed a significant wall motion improvement at follow-up (p = 0.033). Combined imaging by [18F]FDG-PET/MR showed a fair accuracy in predicting myocardial recovery after CTO revascularisation (PET/MR area under ROC curve (AUC) = 0.72, p = 0.002), which was superior to LGE-MR (AUC = 0.66) and [18F]FDG-PET (AUC = 0.58) alone. CONCLUSION: Hybrid PET/MR imaging prior to CTO revascularisation predicts more accurately the recovery of dysfunctional myocardium than PET or MR alone. Its complementary information may identify regions of viable myocardium with increased potential for functional recovery.

Evaluation of a shortened cardiac MRI protocol for left ventricular examinations: diagnostic performance of T1-mapping and myocardial function analysis.

BACKGROUND: In this study we sought to retrospectively evaluate whether a very brief cardiac magnetic resonance imaging (CMR) protocol sufficiently distinguishes patients with relevant myocardial changes with need for further examination from healthy subjects. METHODS: Patients with clinical indication for CMR (n = 160) were included in the study. Patients were categorized into two groups depending on presence of left ventricular (LV) dysfunction. ROC-analysis was done for results of T1-, T2- mapping and extracellular volume evaluation in patients without LV dysfunction. Binary endpoint was correctly depicted pathology of the conventional qualitative CMR techniques and report. RESULTS: In the patient cohort without LV dysfunction (49%), AUC for T1 mapping was 82% (p < 0.001), 60% for T2 mapping (p = 0.1) and 79% for ECV (p < 0.001). T1 mapping was significantly superior to T2 mapping to rule out left ventricular pathology (p = 0.012). Sensitivity for the combined use of T1 mapping and sBTFE cine imaging was 98%; the negative predictive value was 90%. In 49 patients (30%) full protocol CMR did not provide any additional information; T1 mapping correctly detected 57% of the subjects from this group who would not benefit from additional CMR. CONCLUSION: A shortened CMR protocol comprising T1 mapping and LV-function analysis seems suitable to rule out myocardial alterations. Every third patient of the study population did not benefit from full contrast enhanced CMR. The shortened protocol correctly identified every fifth patient who would not benefit but no relevant pathologic findings with the obligation for treatment were missed.

EP3 (prostaglandin E2 receptor 3) expression is a prognostic factor for progression-free and overall survival in sporadic breast cancer.

BACKGROUND: In various cancers, overexpression of cyclooxygenase (COX)-2 and elevated prostaglandin (PG) E2 synthesis have been associated with tumor development and progression. The potential of COX-2 inhibitors in cancer prevention and treatment has been shown repeatedly; however, their clinical use is limited due to toxicity. PGE2 signals via EP receptors 1-4, whose functions are analyzed in current research in search for targeted anti-PG therapies. EP2 and EP4 rather promote tumorigenesis, while the role of EP3, especially in breast cancer, is not yet clear and both pro- and anti-tumorigenic effects have been described. Our study evaluates EP3 receptor expression in sporadic breast cancer and its association with clinicopathological parameters, progression-free and overall survival. METHODS: Two hundred eighty-nine sporadic breast cancer samples without primary distant metastasis were immunohistochemically analyzed for EP3 receptor expression. Tissue was stained with primary anti-EP3-antibodies. Immunoreactivity was quantified by the immunoreactivity-score (IRS); samples with an IRS ≥ 2 scored as EP3 positive. Chi-squared and Mann-Whitney-U test were used for comparison of data; Kaplan-Meier estimates and Cox-regression were used for survival analyses. RESULTS: EP3 receptor was expressed in 205 of 289 samples analyzed (70.9%). EP3 receptor expression was not associated with clinicopathological parameters (e. g. tumor size, hormone receptors, lymph node status). Kaplan-Meier estimates showed a significant association of EP3 positivity with improved progression-free survival (p = 0.002) and improved overall survival (p = 0.001) after up to 10 years. Cox regression analysis confirmed EP3 positivity as a significant prognostic factor even when other known prognosticators were accounted for. CONCLUSIONS: In sporadic breast cancer, EP3 receptor expression is not significantly associated with clinicopathological parameters but is a significant prognostic factor for improved progression-free and overall survival. However, the functional aspects of EP3 receptor in breast cancer and the way how EP3 may oppose the pro-tumorigenic effects of PGE2 elevation and COX-2 overexpression are not fully understood so far. Further studies aiming at identification of the factors regulated by EP3 are necessary to evaluate the possibility of targeting EP3 in future anti-tumor therapy in breast cancer.

Use of drug-eluting balloon coronary intervention prior to living donor kidney transplantation.

BACKGROUND: Kidney transplantation is the gold standard of therapy in patients with terminal renal insufficiency. Living donor transplantation is a well-established option in this field. Enlarging the donor's pool implicates the acceptance of an increased rate of comorbidities. Among them, coronary artery disease is a growing problem. An increasing number of patients, undergoing living donation, receive antiplatelet therapies due to coronary disease. CASE PRESENTATION: Here we report about the perioperative treatment with a drug-eluting balloon in a patient with major cardiac risk factors who underwent kidney transplantation. CONCLUSION: At the current time no recommendation can be given for the routine use of drug-eluting balloons.

Influence of gender on postoperative outcome after intra-aortic balloon counter-pulsation and cardiac surgery.

INTRODUCTION: Female gender is an established risk factor for worse outcomes after cardiac surgery, and women are more likely to experience postoperative complications. Our aim was to analyze the influence of gender on outcome and postoperative complications after the use of intra-aortic balloon counter-pulsation (IABP) in cardiac surgery patients. METHODS: Fifty-seven consecutive female patients (mean age: 73 ± 9 years) requiring an IABP at our department from January 2007 to January 2010 were retrospectively analyzed and compared with 182 male patients receiving IABP support within the same period. The collected data included patient demographics, preoperative state, operative details, postoperative pharmacological treatment, IABP-associated complications, and inhospital mortality. Preoperative mortality risk was calculated by logistic EuroSCORE. RESULTS: There were no differences regarding the type of operation, preoperative renal or hepatic failure, though the prevalence of peripheral artery occlusive disease was higher in men. Furthermore, female patients receiving an IABP were significantly older (73 ± 9 vs. 67 ± 10 years), had a higher ejection fraction (EF) (45% ± 24% vs. 36% ± 14%), and had a higher EuroSCORE (25% ± 20% vs. 19% ± 17%; p < 0.05). Postoperative catecholamine support was significantly higher in the female patients. Women had a prolonged length of stay (LOS) at the ICU (10.64 ± 9.7 vs. 7.6 ± 7.6 days), higher incidence of renal replacement therapy, and a higher mortality (19 [19.4%] vs. 35 [33.9%]; p < 0.05) after the use of IABP. CONCLUSION: Women have a worse outcome after the use of IABP, including LOS at the ICU, postoperative renal failure, and inhospital mortality, despite higher EF, when compared with men.

Glucocorticoid-endocannabinoid interaction in cardiac surgical patients: relationship to early cognitive dysfunction and late depression.

BACKGROUND: Endocannabinoids (ECs) are rapidly acting immune-modulatory lipid-signaling molecules that are important for adaptation to stressful and aversive situations.They are known to interact with glucocorticoids and other stress-responsive systems. Maladaptation to acute or chronic stress represents a major risk factor for the development of psychiatric disorders. In the present study, we administered stress doses of hydrocortisone ina prospective, randomized, placebo-controlled double blind study in patients undergoing cardiac surgery (CS) to examine the relationship between the use of glucocorticoids, plasma EC levels, and the occurrence of early postoperative cognitive dysfunction (delirium) and of later development of depression. METHODS: We determined plasma levels of the ECs anandamide and 2-arachidonoylglycerol (2-AG) in CS patients of the hydrocortisone (n=56) and the placebo group(n=55) preoperatively, at postoperative day (POD) 1, at intensive care unit discharge, and at 6 months after CS(n=68). Postoperative delirium was diagnosed according to Diagnostic and Statistical Manual of the American Psychiatric Association IVth Edition (DSM-IV) criteria, and depression was determined by validated questionnaires and a standardized psychological interview (Structured Clinical Interview for DSM-IV). RESULTS: Stress doses of hydrocortisone did not affect plasma EC levels and the occurrence of delirium or depression. However, patients who developed deliriumon POD 1 had significantly lower preoperative 2-AG levels of the neuroprotective EC 2-AG (median values, 3.8 vs. 11.3ng/ml; p=0.03). Preoperative 2-AG concentrations were predictive of postoperative delirium (sensitivity=0.70;specificity=0.69; cutoff value=4.9 ng/ml; receiver operating characteristic curve area=0.70; 95 o/o confidence interval=0.54-0.85). Patients with depression at 6 months after CS (n=16) had significantly lower anandamide and 2-AG levels during the perioperative period. CONCLUSIONS: A low perioperative EC response may indicate an increased risk for early cognitive dysfunction and long-term depression in patients after CS. Glucocorticoids do not seem to influence this relationship.

Corticosteroid resistance in sepsis is influenced by microRNA-124--induced downregulation of glucocorticoid receptor-α.

OBJECTIVE: Acquired glucocorticoid resistance frequently complicates the therapy of sepsis. It leads to an exaggerated proinflammatory response and has been related to altered expression profiles of glucocorticoid receptor isoforms glucocorticoid receptor-α (mediating anti-inflammatory effects) and glucocorticoid receptor-ß (acting as a dominant negative inhibitor). We investigated the impact of glucocorticoid receptor isoforms on glucocorticoid effects in human T-cells. We hypothesized that 1) changes of the ratio of glucocorticoid receptor isoforms impact glucocorticoid resistance and 2) glucocorticoid receptor-α expression is controlled by microRNA-mediated gene silencing. DESIGN: Laboratory-based study. SETTING: University research laboratory. SUBJECTS AND PATIENTS: Healthy volunteers, sepsis patients. METHODS: First, T-cells from healthy volunteers (native and CD3/CD28-stimulated cells with or without addition of hydrocortisone) were analyzed for the expression of glucocorticoid receptor-isoforms by quantitative polymerase chain reaction. Additionally, effects of gene silencing of glucocorticoid receptor-ß by siRNA transfection were determined. Secondly, microRNA-mediated silencing was evaluated by cloning of a glucocorticoid receptor-α-specific 3'-untranslated-region reporter construct and subsequent transfection experiments in cell cultures. Effects of miRNA transfection on glucocorticoid receptor-α expression were analyzed in Jurkat T-cells and in T-cells from healthy volunteers (quantitative polymerase chain reaction and Western blotting). Finally, expression of glucocorticoid receptor-α, glucocorticoid receptor-ß, and miR-124 was tested in T-cells of sepsis patients (n=24). MEASUREMENTS AND MAIN RESULTS: Stimulation of T-cells induced a significant upregulation of glucocorticoid receptor-α (not glucocorticoid receptor-ß) thereby possibly rendering T-cells more sensitive to glucocorticoids; this T-cell response was hindered by hydrocortisone. Silencing of glucocorticoid receptor-ß doubled the inhibitory effects of glucocorticoids on interleukin-2 production. MicroRNA-124 was proved to specifically downregulate glucocorticoid receptor-α. Furthermore, a glucocorticoid-induced three-fold upregulation of microRNA-124 was found. T-cells of sepsis patients exhibited slightly decreased glucocorticoid receptor-α and slightly increased miR-124 expression levels, whereas glucocorticoid receptor-ß expression was two-fold upregulated (p<.01) and exhibited a remarkable interindividual variability. CONCLUSIONS: Glucocorticoid treatment induces expression of miR-124, which downregulates glucocorticoid receptor-α thereby limiting anti-inflammatory effects of glucocorticoids. Steroid treatment might aggravate glucocorticoid resistance in patients with high glucocorticoid receptor-ß levels.

Medical suppression of hypercortisolemia in Cushing's syndrome with particular consideration of etomidate.

Cushing's syndrome is associated with excessive cortisol secretion by the adrenal gland or ectopic tumours and may result in diabetes, hypertension, and life-threatening infections with high mortality rates especially in the case of surgical resection. Although surgical resection is the treatment of choice, patients may benefit from preceding medical therapy. This may especially be useful as an adjunctive approach in emergency settings, if patients cannot undergo surgery, if surgery or radiotherapy fails, or if the tumour recurs. Medical therapy can be categorized in three different groups-inhibition of steroidogenesis, suppression of adrenocorticotropic hormone, and antagonism of the glucocorticoid receptor. However, the majority of common drugs are not available for parenteral administration, which may evoke a management problem in emergency settings or in patients unable to tolerate oral medication. The carboxylated imidazole etomidate is a well known parenteral induction agent for general anaesthesia. Besides its hypnotic properties, etomidate also has α-adrenergic characteristics and inhibits the enzyme 11-deoxycortisol ß-hydroxylase, which catalyzes the final step of the conversion of cholesterol to cortisol. Adverse outcomes have been reported when used for sedation in septic or trauma patients probably by its interference with steroid homeostasis. However, its capability of inhibition of the 11-deoxycortisol ß-hydroxylase leads to suppression of cortisol secretion which has been demonstrated to be a useful tool in severe and complicated hypercortisolemia. Within this article, we review the data concerning different pharmacological approaches with particular consideration of etomidate in order to suppress steroidogenesis in patients with Cushing's syndrome.

Coronary plaque characterization assessed by delayed enhancement dual-layer spectral CT angiography and optical coherence tomography.

This study aimed to prospectively evaluate delayed enhancement imaging by spectral computed tomography using soluble iodine containing contrast media to improve the in vivo characterization of coronary plaque types based on the quantification of delayed iodine enhancement. Patients with known or suspected coronary artery disease (CAD) underwent spectral coronary CT-angiography (SCCTA). Absolute delayed iodine enhancement in all visible coronary plaques was assessed. Patients with significant CAD (> 50% stenosis) further underwent invasive coronary angiography (ICA) including optical coherence tomography (OCT). We identified 50 non-calcified coronary plaques in 72 patients undergoing SCCTA. 17 patients with significant CAD underwent further ICA including OCT imaging. In those, we were able to match 35 plaques by both SCCTA and OCT. Based on OCT imaging, 22/35 matched plaques (63%) were characterized as high-risk coronary plaques (thin-cap fibroatheroma n = 2, fibroatheroma n = 20), whereas 13/35 (37%) were characterized as low-risk plaques (fibrocalcific lesion n = 3, fibrous plaques n = 9, and early-onset fibroatheroma n = 1). All plaques showed similar HU's and could not be classified into high-risk or low-risk plaques by conventional CT measures. Minimal delayed iodine enhancement within plaques as quantified by SCCTA demonstrated significantly lower values in high-risk as compared to low-risk coronary plaques (1.0 ± 1.5 mg/ml vs. 2.2 ± 1.1 mg/ml, p = 0.021) which allowed estimation of high-risk plaques with high sensitivity and moderate specificity (77% and 56%). Measurement of delayed enhancement iodine uptake within stable coronary artery plaques using dual-layer SCCTA might contribute to a more precise estimation of plaque vulnerability surpassing conventional CT techniques.

Relationship of a common polymorphism of the glucocorticoid receptor gene to traumatic memories and posttraumatic stress disorder in patients after intensive care therapy.

OBJECTIVE: Glucocorticoids play a major role in the consolidation and retrieval of traumatic information. They act through the glucocorticoid receptor, for which, in humans, several polymorphisms have been described. In particular, the BclI single-nucleotide polymorphism is associated with hypersensitivity to glucocorticoids and with susceptibility to development of major depression. Furthermore, in patients with posttraumatic stress disorder carrying the BclI GG genotype, cortisol levels were lower and showed an inverse relationship to posttraumatic stress disorder symptom intensity. Here, we studied the association of the BclI polymorphism with plasma cortisol levels, traumatic memories, posttraumatic stress disorder symptoms, and health-related quality of life outcomes in 126 patients undergoing cardiac surgery and intensive care unit therapy. DESIGN: Prospective observational study. SETTING: Cardiovascular intensive care unit in a university hospital. PATIENTS: A total of 126 patients undergoing cardiac surgery and intensive care unit treatment. INTERVENTIONS: No interventions were performed. MEASUREMENTS AND MAIN RESULTS: Validated questionnaires were used to quantify end points. Measurements were taken 1 day before and 1 wk and 6 months after cardiac surgery. Homozygous carriers of the BclI G allele (n = 21) had significantly lower preoperative plasma cortisol levels and more long-term traumatic memories from intensive care unit therapy at 6 months after cardiac surgery than heterozygous carriers or noncarriers (1.9 ± 1.4 vs. 1.0 ± 1.2, p = .01). Anxiety was significantly more common as a long-term traumatic memory in homozygous BclI G allele carriers than in heterozygous carriers or noncarriers (57% vs. 35%, p = .03). Posttraumatic stress disorder symptom scores were significantly higher at discharge from the intensive care unit in homozygous BclI G allele carriers than in heterozygous carriers or noncarriers. Only heterozygous carriers or BclI G allele noncarriers had a significant gain in health-related quality of life physical function at 6 months after cardiac surgery (p < .01). Baseline values were not statistically different between carriers of the different BclI alleles. CONCLUSION: Homozygous BclI G allele carriers are at risk for traumatic memories, posttraumatic stress disorder symptoms, and lower health-related quality of life after cardiac surgery and intensive care unit therapy. The BclI single-nucleotide polymorphism may help to identify individuals at need for tailored medical care.

Early Bronchoscopy Improves Extubation Rates after Out-of-Hospital Cardiac Arrest: A Retrospective Cohort Analysis.

BACKGROUND: Patients suffering from out-of-hospital cardiac arrest (OHCA) frequently receive a bronchoscopy after being admitted to the ICU. We investigated the optimal timing and the outcome in these patients. METHODS: All patients who suffered from OHCA and were treated in our ICU from January 2013 to December 2018 were retrospectively analyzed. The data were collected from the patients' medical files, and included duration of mechanical ventilation, antibiotics, microbiological test results and neurological outcome. The outcome was the effect of early bronchoscopy (≤48 h after administration) on the rate of intubated patients on day five and day seven. RESULTS: From January 2013 to December 2018, 190 patients were admitted with OHCA. Bronchoscopy was performed in 111 patients out of the 164 patients who survived the first day. Late bronchoscopy >48 h was associated with higher rates of intubation on day five (OR 4.94; 95% CI 1.2-36.72, 86.7% vs. 55.0%, p = 0.036) and day seven (OR 4.96; 95% CI 1.38-24.69; 80.0% vs. 43.3%, p = 0.019). CONCLUSION: This study shows that patients who suffered from OHCA might have a better outcome if they receive a bronchoscopy early after hospital admission. Our data suggests an association of early bronchoscopy with a shorter intubation period.

Substantially altered expression pattern of cannabinoid receptor 2 and activated endocannabinoid system in patients with severe heart failure.

Animal studies suggest that the endocannabinoid system (ECS) plays a role in the regulation of myocardial contractility and in the pathogenesis of heart failure. The current study aimed to proof the existence of endocannabinoid receptors on human ventricular myocardium and to determine whether human chronic heart failure (CHF) is associated with changes in endocannabinoid receptor expression and distribution. Expression of cannabinoid receptor 1 (CB1) and cannabinoid receptor (CB2) on human heart was assessed by means of real-time PCR and immunohistochemistry. On healthy human left ventricular myocardium, mRNA transcripts of CB1 and CB2 receptors were expressed in an almost equal proportion. In patients with CHF, mRNA expression of CB1 receptors was shown to be downregulated 0.7-fold (0.7.+/-0.15, n=12, p<0.01), whereas expression of CB2 receptors was upregulated more than 11-fold (11.6+/-4.5; n=12; p<0.005). Corresponding results were obtained by immunohistochemistry. Blood levels of endocannabinoids were significantly elevated (anandamide 3.5-fold (p<0.001); 2-AG 7-fold (p=0.02)) in patients with CHF, as compared to healthy volunteers. Both CB1 and CB2 receptors are present on healthy human left ventricular myocardium in a balanced distribution. Patients suffering from CHF exhibit a shift of the CB1-CB2 receptor ratio towards expression of CB2 receptors combined with significantly elevated peripheral blood levels of endocannabinoids indicating an activation of the ECS. These results might open up new perspectives regarding the role of endocannabinoid signalling in CHF and its potential as a target for pharmacological modulation.

Noninvasive mechanical ventilation in patients with acute respiratory failure after cardiac surgery.

OBJECTIVE: To evaluate the feasibility and outcomes of protocol-driven noninvasive mechanical ventilation in patients with acute respiratory failure (ARF) after cardiac surgery. METHODS: From 2001 to 2004, a total of 2428 cardiac surgery patients admitted to our intensive care unit were observed. After exclusion of patients who received tracheostomy or were discharged while still on mechanical ventilation, 2261 patients with spontaneous breathing were further evaluated for ARF. Patients diagnosed with ARF were treated with intermittent noninvasive mechanical ventilation (NIV) if possible. Risk factors for the development of postoperative ARF as well as outcomes in patients with and without ARF were analyzed. RESULTS: In 2261 spontaneously breathing postoperative cardiac surgical patients after primarily successful extubation, 799 patients (35%) were diagnosed with ARF. Fifty-six patients (7%) did not tolerate NIV treatment. In 743 patients (33%) intermittent NIV was performed. In patients with ARF, ejection fraction was lower, combined cardiac surgical procedures were more frequent, postoperative mechanical ventilation time was longer, and the severity of illness score (SAPS II) was higher (P < .05). The duration of catecholamine support was longer, and the transfusion rate was higher in the NIV group (P < .05); however, mortality did not differ between patients with ARF treated by NIV and patients without ARF. CONCLUSION: Our study demonstrates the feasibility of NIV in patients after cardiac surgery. These results might suggest that NIV should be considered as first-line ventilatory support in ARF after cardiac surgery. A large randomized trial is warranted to confirm these findings.

Stress doses of hydrocortisone in high-risk patients undergoing cardiac surgery: effects on interleukin-6 to interleukin-10 ratio and early outcome.

BACKGROUND: Severe systemic inflammation (systemic inflammatory response syndrome) associated with cardiac surgery often leads to a worse short-term and long-term outcome. Stress doses of hydrocortisone have been successfully used to improve outcome of CS. The interleukin (IL)-6 to IL-10 ratio is associated with outcome after trauma and major surgery. OBJECTIVE: To evaluate immunologic effects (especially IL-6 to IL-10 ratio) of stress doses of hydrocortisone in a high-risk group of patients after cardiac surgery with cardiopulmonary bypass. DESIGN: Prospective, randomized, double-blinded, placebo-controlled trial. SETTING: Cardiovascular intensive care unit of a university hospital. PATIENTS: High-risk patients (n = 36) undergoing CS. INTERVENTION: Stress doses of hydrocortisone or placebo. MAIN OUTCOME MEASURES: IL-6 to IL-10 ratio and other markers of systemic inflammation at predefined time points; short-term clinical outcome. RESULTS: The two study groups did not differ with regard to demographic data. The patients from the hydrocortisone group (n = 19) had significantly lower levels of IL-6 and higher levels of IL-10, resulting in an attenuated change in IL-6/IL-10 ratio (28.7 [6.4/128.7] vs. 292.8 [6.5/534.6] 4 hours after cardiopulmonary bypass; p < 0.001). Patients in the hydrocortisone group had a shorter duration of catecholamine support (1 [1/2] vs. 4 [2/4.5] days; p = 0.02), a shorter length of stay in the intensive care unit (2 [2/3] vs. 6 [4/8] days; p = 0.001), and a lower incidence of postoperative atrial fibrillation (26% vs. 59%; p = 0.04). CONCLUSIONS: Stress doses of hydrocortisone attenuate the evolution of IL-6/IL-10 ratio in patients with systemic inflammatory response syndrome after CS, which seems to be associated with an improved outcome. The immunologic effects of hydrocortisone may thus be both, inhibitory (IL-6) and permissive (IL-10), regarding the immune response.

Extracorporeal support in a patient with cardiogenic shock due to Aerococcus urinae endocarditis.

Aerococcus urinae is a newly identified Gram-positive coccus that causes serious infections. To date, only 15 cases of A. urinae infective endocarditis have been reported, but with a very high mortality. The case is reported of a patient with A. urinae double valve endocarditis. Following aortic and mitral valve replacement, the patient suffered from refractory cardiogenic shock; extracorporeal membrane oxygenation was used successfully as a rescue mechanical support.

Hirudin for management of heparin-induced thrombocytopenia type II in a patient with biventricular assist device support.

A patient with severe dilated cardiomyopathy developed heparin-induced thrombocytopenia type II (HIT II) after implantation of a biventricular assist device (biVAD). Because the patient showed mild renal dysfunction but severe hepatic impairment, the management of anticoagulation was switched from heparin to the direct thrombin inhibitor hirudin, which was administered by continuous infusion of 0.6 to 1 mg/h. This protocol was monitored by measuring the plasma hirudin level, which ranged from 0.5 to 1.5 microg/mL. Unfortunately, the patient died on day 22 after implantation from fulminant sepsis caused by Aspergillus fumigatus. Neither thromboembolic events nor thrombocytopenia was observed after hirudin administration. The explanted biVAD showed no thrombotic material in the arterial/venous lines or on the polyurethane valves. We discuss the challenges posed by HIT II complicating VAD support as well as its clinical management with direct thrombin inhibitors.

Heparin-induced thrombosis without thrombocytopenia causing fulminant pulmonary embolism after off-pump coronary artery bypass grafting.

Heparin-induced thrombocytopenia (HIT) is a rare immune-mediated complication of heparin administration. A potentially life-threatening complication, HIT is difficult to diagnose in patients in the intensive care unit after cardiac surgery because there can be multiple reasons for thrombocytopenia. Moreover, immune-mediated platelet consumption may be masked by reactive thrombocytosis, which is common in the typical postoperative course after cardiac surgery. We report the case of a 57-year-old male patient who developed fulminant pulmonary embolism following heparin-induced thrombosis without thrombocytopenia after off-pump coronary artery bypass surgery.

Preinterventional hydrocortisone sustains the endothelial glycocalyx in cardiac surgery.

BACKGROUND: Patients undergoing cardiac surgery commonly develop systemic inflammation associated with tissue edema, which impairs outcome. One main pathomechanism leading to the edema is the deterioration of the endothelial glycocalyx, a key component of the vascular barrier. In animal models hydrocortisone has proved to be protective for the glycocalyx. OBJECTIVE: This trial evaluates the effect of hydrocortisone on glycocalyx integrity in patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: In a prospective, randomized interventional pilot trial, 30 patients received either hydrocortisone (100 mg over 10 min) or placebo (saline control) before surgery. Plasma concentrations of glycocalyx constituents (syndecan-1, heparan sulfate) and various clinical parameters (respiratory and renal function, inflammatory markers, use of vasopressors, length of stay at the intensive care unit) were measured. Primary endpoint was a significant difference of glycocalyx constituents in plasma. Comparisons were made with Friedman's and Wilcoxon tests (paired data), or the Kruskal-Wallis and Mann-Whitney U tests (unpaired data). Holm-Bonferroni method was used for post-hoc corrections. RESULTS: Heparan sulfate and syndecan-1 increased significantly during and after cardiac surgery with cardiopulmonary bypass in both groups. Whereas the maximum increase of heparan sulfate was 12.3-fold in the control vs. 3.8-fold in the pretreated group (p < 0.05), syndecan-1 values showed no significant difference between the groups (maximal increase 3-fold). The inflammatory markers C-reactive protein and interleukin-6 were also higher in the control than in the hydrocortisone group, but there was no difference in patient mortality (zero), or in any clinical parameters. CONCLUSIONS: Pretreatment with hydrocortisone ameliorated shedding of heparan sulfate, a major constituent of the endothelial glycocalyx, in patients undergoing cardiac surgery with cardiopulmonary bypass, but had no relevant influence on various clinical parameters or patient mortality. The relatively small number of patients in this pilot study probably precluded detection of positive outcome differences.

Daptomycin, a lipopeptide antibiotic in clinical practice.

Gram-positive cocci are one of the leading causes of infections in clinical medicine. Since the invention of antibiotic substances, multidrug resistance is a major problem in the treatment of such infections. Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for 60% of nosocomial infections in the US. The first-choice drug used in these cases is the glycopeptide vancomycin; however, vancomycin is associated with a significant number of adverse side effects, such as nephro- and ototoxicity. Thus, the discovery of new drugs against MRSA and other multidrug-resistant cocci is of utmost interest. Daptomycin, a lipopeptide, is one of these new drugs and has been successfully used in the treatment of complicated skin and skin-structure infections and right-sided endocarditis. Because of its potency and pharmacological profile, it is increasingly used for new indications not yet approved by the FDA. The purpose of this article is to provide an overview of daptomycin, with particular emphasis on potential new indications for which it could be used in the future.