[Intrahepatic Hematoma and Pulmonary Embolism in a Young Woman with Oral Contraceptives Complicated by Type II Heparin Induced Thrombocytopenia Requiring ECMO-Therapy: a Case Report]. / Fulminante Lungenarterienembolie bei heparininduzierter Thrombozytopenie Typ II.

A 46-year-old woman on oral contraceptives developed an intrahepatic hematoma due to a benign hepatic tumor. As an incidental finding, a computed tomography showed a pulmonary embolism. Unfractionated heparin was given in a prophylactic dosing in an attempt to balance the risk of further intrahepatic bleeding with that of thrombosis. Ten days later, the patient developed a second pulmonary embolism along with acute right heart failure requiring cardiopulmonary resuscitation. As a sufficient circulation and oxygenation could not be reestablished, a veno-arterial extracorporeal membrane oxygenation (ECMO) was installed. An ELISA-Test, detecting PF4-Heparin associated antibodies, resulted in a positive result for a type II heparin induced thrombocytopenia even in the absence of thrombocytopenia. After hemodynamic and pulmonary stabilization, six days after ECMO-support the cannula was scheduled to be removed. On removal of the venous cannula the patient developed another massive pulmonary embolism with cardiac arrest which led to immediate reinstallation of va-ECMO. Under therapeutic anticoagulation using argatroban the ECMO support continued until the patient was on day 17 successfully weaned.

[Risk factors for adverse reactions after protamine administration in adult patients undergoing cardiac surgery- a case report and literature review]. / Kasuistik mit Literaturübersicht - Protamingabe bei Patientin mit Fischeiweißallergie.

Protamine is a protein mainly used to reverse anticoagulant effects of heparin during cardiac or vascular surgery with extracorporeal circulation. Adverse events after protamine administration are rare but if they occur they can be catastrophic. Based on a case report with an elective cardiac surgery patient with known allergy to fish, we discuss the related events and risk factors for an adverse reaction after protamine. The patient management and its outcome are presented.

Case Report: Traumatic cardiac arrest due to pericardial tamponade: successful pericardiocentesis with a Shaldon catheter.

In this report, we describe the successful resuscitation of a 4-year-old child who suffered a traumatic cardiac arrest during a routine procedure in the operating room. The diagnosis of a sanguineous pericardial tamponade was made by emergency ultrasonography. Consecutive subxiphoid pericardiocentesis with an adult Shaldon catheter led to return of spontaneous circulation. Subsequent thoracotomy and surgical suturing definitively stopped the bleeding from the right ventricle. The combined expertise of all perioperative disciplines was decisive for the patient's survival.

An unusual presentation of invasive Fusarium aortitis in a patient who is immunocompromised: A case report.

Fusarium (F.) species are ubiquitous filamentous fungi that may cause various opportunistic infections, especially in patients who are immunocompromised. A rare manifestation of disseminated fusariosis affects the aortic valve and results in invasive aortitis, which poses a significant challenge for clinicians in diagnosis and treatment. Here, we report a case of a patient, aged 54 years, who is immunocompromised, presenting initially with Fusarium keratitis and chorioretinitis in both eyes and a new endovascular aortic mass. Positron emission tomography/computed tomography was performed, suggesting aortitis. Transoesophageal echocardiography and electrocardiogram-guided computed tomography-angiography confirmed a large intraluminal mass in the ascending aorta. The aortic mass and a part of the ascending aorta were resected surgically, and a filamentous fungus with the microscopic features of the genus Fusarium was isolated and later identified molecularly as F. petroliphilum. The course of the treatment was complicated by perioperative cerebral embolization and mesenteric ischemia. These complications could be attributed to a preoperatively existing occlusion of the superior and inferior mesenteric artery and a subtotal stenosis of the celiac trunk. This case report describes a rare manifestation of disseminated fusariosis, frequently characterized by protracted clinical courses with poor prognosis. Fusariosis may manifest at different sites at different times or persist as a long-lasting disease with reactivation. This case highlights the importance of the interdisciplinary approach for effectively treating invasive mycoses.

Hemoadsorption treatment with CytoSorb® in patients with extracorporeal life support therapy: A case series.

INTRODUCTION: Extracorporeal life support is an increasingly used technique for respiratory and cardiocirculatory support. Besides primary organ dysfunction, an excessive systemic hyperinflammatory response can be the underlying cause for acute organ failure necessitating extracorporeal life support therapy, or it may be associated with the extracorporeal life support itself. Controlling this overwhelming inflammatory response using CytoSorb® hemoadsorption has been shown to be associated with improved hemodynamics and restored metabolic balance resulting in preserved organ functions. METHODS: In this retrospective case series, we describe 23 patients undergoing extracorporeal life support therapy and CytoSorb hemoadsorption. Cytokine levels were monitored, hemodynamic and metabolic variables were recorded, and outcome measures such as duration of organ support, intensive care unit mortality, and hospital mortality were noted. RESULTS: CytoSorb treatment was associated with a trend toward a reduction in plasma cytokine levels (first treatment median interleukin-6 pre 595 vs post 350 pg/mL (n.s.); second treatment median interleukin-6 317 vs 108 pg/mL, p < 0.05), a reduced vasoplegic response resulting in a reduction in vasopressor requirements (first treatment median norepinephrine pre 0.15 vs post 0.02 µg/kg/min (n.s.); second treatment median norepinephrine 0.1 vs 0.02 µg/kg/min, p < 0.05) as well as rebalancing of deranged metabolic parameters (first treatment median lactate pre-treatment 6 vs post-treatment median lactate 2 mmol/L, p < 0.05). The hemoperfusion treatment was well tolerated and safe, without the occurrence of any CytoSorb device-related adverse events. CONCLUSION: Hemoadsorption may offer a potentially promising therapeutic option for critically ill patients undergoing extracorporeal life support therapy, with cytokine reduction and a consecutively mitigated inflammatory response, decreased vasoplegia, and improved organ function as seen in our patients.

Endothelial NOS is required for SDF-1alpha/CXCR4-mediated peripheral endothelial adhesion of c-kit+ bone marrow stem cells.

In the era of intravascular approaches for regenerative cell therapy, the underlying mechanisms of stem cell migration to non-marrow tissue have not been clarified. We hypothesized that next to a local inflammatory response implying adhesion molecule expression, endothelial nitric oxide synthase (eNOS)-dependent signaling is required for stromal- cell-derived factor-1 alpha (SDF-1alpha)-induced adhesion of c-kit+ cells to the vascular endothelium. SDF-1alpha/tumor necrosis factor-alpha (TNF-alpha)-induced c-kit+-cell shape change and migration capacity was studied in vitro using immunohistochemistry and Boyden chamber assays. In vivo interaction of c-kit+ cells from bone marrow with the endothelium in response to SDF-1alpha/TNF-alpha stimulation was visualized in the cremaster muscle microcirculation of wild-type (WT) and eNOS (-/-) mice using intravital fluorescence microscopy. In addition, NOS activity was inhibited with N-nitro-L-arginine-methylester-hydrochloride in WT mice. To reveal c-kit+-specific adhesion behavior, endogenous leukocytes (EL) and c-kit+ cells from peripheral blood served as control. Moreover, intercellular adhesion molecule-1 (ICAM-1) and CXCR4 were blocked systemically to determine their role in inflammation-related c-kit+-cell adhesion. In vitro, SDF-1alpha enhanced c-kit+-cell migration. In vivo, SDF-1alpha alone triggered endothelial rolling-not firm adherence-of c-kit+ cells in WT mice. While TNF-alpha alone had little effect on adhesion of c-kit+ cells, it induced maximum endothelial EL adherence. However, after combined treatment with SDF-1alpha+TNF-alpha, endothelial adhesion of c-kit+ cells increased independent of their origin, while EL adhesion was not further incremented. Systemic treatment with anti-ICAM-1 and anti-CXCR4-monoclonal antibody completely abolished endothelial c-kit+-cell adhesion. In N-nitro-L-arginine-methylester-hydrochloride-treated WT mice as well as in eNOS (-/-) mice, firm endothelial adhesion of c-kit+ cells was entirely abrogated, while EL adhesion was significantly increased. The chemokine SDF-1alpha mediates firm adhesion c-kit+ cells only in the presence of TNF-alpha stimulation via an ICAM-1- and CXCR4-dependent mechanism. The presence of eNOS appears to be a crucial and specific factor for firm c-kit+-cell adhesion to the vascular endothelium.

Enhanced thoracic gene delivery by magnetic nanobead-mediated vector.

BACKGROUND: Systemic gene delivery is limited by the adverse hydrodynamic conditions on the collection of gene carrier particles to the specific area. In the present study, a magnetic field was employed to guide magnetic nanobead (MNB)/polymer/DNA complexes after systemic administration to the left side of the mouse thorax in order to induce localized gene expression. METHODS: Nonviral polymer (poly ethyleneimine, PEI) vector-gene complexes were conjugated to MNBs with the Sulfo-NHS-LC-Biotin linker. In vitro transfection efficacy of MNB/PEI/DNA was compared with PEI/DNA in three different cell lines as well as primary endothelial cells under magnetic field stimulation. In vivo, MNB/PEI/DNA complexes were injected into the tail vein of mice and an epicardial magnet was employed to attract the circulating MNB/PEI/DNA complexes. RESULTS: Endocytotic uptake of MNB/PEI/DNA complexes and intracellular gene release with nuclear translocation were observed in vitro, whereas the residues of MNB/PEI complexes were localized at the perinuclear region. Compared with PEI/DNA complexes alone, MNB/PEI/DNA complexes had a 36- to 85-fold higher transfection efficiency under the magnetic field. In vivo, the epicardial magnet effectively attracted MNB/PEI/DNA complexes in the left side of the thorax, resulting in strong reporter and therapeutic gene expression in the left lung and the heart. Gene expression in the heart was mainly within the endothelium. CONCLUSIONS: MNB-mediated gene delivery could comprise a promising method for gene delivery to the lung and the heart.

Assessment and pathophysiology of pain in cardiac surgery.

Analysis of the problem of surgical pain is important in view of the fact that the success of surgical treatment depends largely on proper pain management during the first few days after a cardiosurgical procedure. Postoperative pain is due to intraoperative damage to tissue. It is acute pain of high intensity proportional to the type of procedure. The pain is most intense during the first 24 hours following the surgery and decreases on subsequent days. Its intensity is higher in younger subjects than elderly and obese patients, and preoperative anxiety is also a factor that increases postoperative pain. Ineffective postoperative analgesic therapy may cause several complications that are dangerous to a patient. Inappropriate postoperative pain management may result in chronic pain, immunosuppression, infections, and less effective wound healing. Understanding and better knowledge of physiological disorders and adverse effects resulting from surgical trauma, anesthesia, and extracorporeal circulation, as well as the development of standards for intensive postoperative care units are critical to the improvement of early treatment outcomes and patient comfort.

Hemoadsorption treatment of patients with acute infective endocarditis during surgery with cardiopulmonary bypass - a case series.

INTRODUCTION: Infective endocarditis is a serious disease condition. Depending on the causative microorganism and clinical symptoms, cardiac surgery and valve replacement may be needed, posing additional risks to patients who may simultaneously suffer from septic shock. The combination of surgery bacterial spreadout and artificial cardiopulmonary bypass (CPB) surfaces results in a release of key inflammatory mediators leading to an overshooting systemic hyperinflammatory state frequently associated with compromised hemodynamic and organ function. Hemoadsorption might represent a potential approach to control the hyperinflammatory systemic reaction associated with the procedure itself and subsequent clinical conditions by reducing a broad range of immuno-regulatory mediators. METHODS: We describe 39 cardiac surgery patients with proven acute infective endocarditis obtaining valve replacement during CPB surgery in combination with intraoperative CytoSorb hemoadsorption. In comparison, we evaluated a historical group of 28 patients with infective endocarditis undergoing CPB surgery without intraoperative hemoadsorption. RESULTS: CytoSorb treatment was associated with a mitigated postoperative response of key cytokines and clinical metabolic parameters. Moreover, patients showed hemodynamic stability during and after the operation while the need for vasopressors was less pronounced within hours after completion of the procedure, which possibly could be attributed to the additional CytoSorb treatment. Intraoperative hemoperfusion treatment was well tolerated and safe without the occurrence of any CytoSorb device-related adverse event. CONCLUSIONS: Thus, this interventional approach may open up potentially promising therapeutic options for critically-ill patients with acute infective endocarditis during and after cardiac surgery, with cytokine reduction, improved hemodynamic stability and organ function as seen in our patients.

Cytokine Reduction in the Setting of an ARDS-Associated Inflammatory Response with Multiple Organ Failure.

A 45-year-old male was admitted to our hospital with a small bowel obstruction due to torsion and was immediately scheduled for surgical intervention. At anesthesia induction, the patient aspirated and subsequently developed a severe SIRS with ARDS and multiple organ failure requiring the use of ECMO, CRRT, antibiotics, and low dose steroids. Due to a rapid deterioration in clinical status and a concurrent surge in inflammatory biomarkers, an extracorporeal cytokine adsorber (CytoSorb) was added to the CRRT blood circuit. The combined treatment resulted in a rapid and significant reduction in the levels of circulating inflammatory mediators. This decrease was paralleled by marked clinical stabilization of the patient including a significant improvement in hemodynamic stability and a reduced need for norepinephrine and improved respiratory function as measured by PaO2/FIO2, ventilator parameters, lung mechanics, and indirect measures of capillary leak syndrome. The patient could be discharged to a respiratory weaning unit where successful respiratory weaning could be achieved later on. We attribute the clinical improvement to the rapid control of the hyperinflammatory response and the reduction of inflammatory mediators using a combination of CytoSorb and these other therapies. CytoSorb treatment was safe and well tolerated, with no device-related adverse effects observed.

Treatment of post-cardiopulmonary bypass SIRS by hemoadsorption: a case series.

The use of cardiopulmonary bypass (CPB) in cardiothoracic surgery results in a well-known activation of the immunologic response. In some cases, however, this triggered immunologic response may be excessive, leading to a severe systemic inflammatory response syndrome (SIRS) and induced organ dysfunction. For example, patients frequently develop hemodynamic instability with hypotension and low systemic vascular resistance. To date, different therapeutic approaches, such as steroids, have been tried to control this maladaptive postoperative SIRS response, yet definitive proof of clinical efficacy is missing. A new cytokine adsorber device (CytoSorb; CytoSorbents) may be a useful approach to control hyperinflammatory systemic reactions by reducing a broad range of proinflammatory cytokines and other inflammatory mediators. This may, in turn, help to reestablish a physiologic immune response and help to restore deranged clinical parameters in these patients. In this retrospective case series study, we describe 16 cardiac surgery patients following prolonged CPB with post-CPB SIRS and subsequent acute kidney injury, who were then treated with hemoadsorption using CytoSorb in combination with continuous renal replacement therapy (CRRT). Treatment of patients with CytoSorb who presented with severe post-CPB SIRS resulted in a reduction of elevated cytokine levels, which was associated with a clear stabilization of deranged hemodynamic, metabolic, and organ function parameters. Treatment was well tolerated and safe, with no device-related adverse events occurring. CytoSorb therapy combined with CRRT is a potentially promising new treatment approach to achieve hemodynamic stability, cytokine reduction, and improved organ function in cardiac surgery patients who develop post-CPB SIRS.

Placement of a left ventricular assist device in a patient with dextrocardia.

Dextrocardia most commonly presents in the setting of situs inversus, but it may occur as an isolated anomaly with normal position of the abdominal organs. Herein we present a 54-year-old man with ischemic cardiomyopathy and dextrocardia with normal position of the abdominal organs who presented with an exacerbation of congestive heart failure requiring inotropic support as well as mechanical ventilation. An implantable, wearable left ventricular assist device was placed in this patient to allow for ambulation and eventual discharge home. The patient survived 4 months before he developed pneumonia and expired.

Role of mast cells and their mediators in failing myocardium under mechanical ventricular support.

BACKGROUND: Mast cells have been implicated in tissue remodeling and fibroblast stimulation. We explored the effect of mechanical support by left ventricular assist device (LVAD) in failing myocardium and looked into grade and distribution of interstitial fibrosis, mast cell density, mast cell phenotypes and basic fibroblast growth factor (bFGF) expression pre- and post-LVAD. METHODS: Myocardial tissue was obtained from 20 patients with end-stage cardiomyopathy at the time of LVAD implantation and LVAD removal and from 7 donor hearts not used for transplantation. Tissue sections were stained for mast cells using tryptase as a marker and the myocardial fibrosis was measured. Double staining for tryptase and chymase was performed for detection of chymase-positive mast cells. Fluorescent microscopy showed the relationship of mast cells to bFGF, and bFGF expression was quantified by Western blot. RESULTS: There was a significant increase in mast cells in heart failure vs normal myocardium. A secondary increase in mast cells occurred after long-term (>40 days) support compared with matched pre-LVAD samples (mean +/- SEM; 57.4 +/- 8.6 cells/10 fields vs 45.1 +/- 7.6 SEM cells/10 fields, p < 0.01). The secondary increase in mast cells was associated specifically with an increase in chymase-negative mast cells (p < 0.01). These findings are statistically significant with concurrent decreased expression of bFGF and decreased fibrosis in the same patient tissues (p < 0.01). CONCLUSIONS: We suggest that, under long-term support, there is a change in phenotypic expression in mast cells, which can alter fibroblast functions. The decreased myocardial bFGF levels might be the result of these phenotypically altered mast cells.

Papillary fibroelastoma of the aortic wall with partial occlusion of the right coronary ostium.

Papillary fibroelastomas are the most common cardiac valve tumors, although they represent less than 10% of all cardiac tumors. These benign tumors are increasingly incidentally discovered as the result of the widespread use of echocardiography. After a definitive diagnosis has been made, surgical resection is strongly advocated due to the risk of cardioembolic complications. We present a very rare finding of an aortic wall papillary fibroelastoma with a resultant partial occlusion of the right coronary ostium.

Aortic valve endocarditis due to abiotrophia defectiva: a rare etiology.

Abiotrophia defectiva is a rare cause of infective endocarditis. Besides an association with often negative blood cultures and difficult treatment, high rates of relapse and higher mortality than endocarditis caused by other viridans streptococci are known features of this entity. We report on the surgical and medical management of the aortic valve endocarditis caused by Abiotrophia defectiva in a 19-year-old patient. To the best of our knowledge, this is the first case of a patient to have Down syndrome and Abiotrophia defectiva endocarditis requiring aortic valve replacement.

Minimizing cardiopulmonary bypass attenuates myocardial damage after cardiac surgery.

The standard heart-lung machine is deemed a major trigger of systemic inflammatory reactions, potentially inducing organ failure. The strict reduction of blood-artificial surface and blood-air contact might represent meaningful improvements of the extracorporeal technology with respect to organ preservation. In this study, we assessed perioperative myocardial damage by using a novel minimal extracorporeal circuit (MECC) and a conventional cardiopulmonary bypass (CPB) system. Sixty patients scheduled for coronary artery bypass surgery were randomly assigned to either the MECC or the standard CPB system. Myocardial markers were determined by specific immunoassays 6, 12, and 24 hours after CPB initiation. Results were corrected for hemodilution.Demographics, hemodynamics, the number of anastomoses, CPB, and cross-clamp time were comparable between the groups. MECC patients demonstrated significantly lower levels of Troponin T (ng/ml) at 6, 12, and 24 hours (0.07 +/- 0.01 vs. 0.16 +/- 0.04, p < 0.005; 0.12 +/- 0.03 vs. 0.28 +/- 0.08, p < 0.008; 0.21 +/- 0.05 vs. 0.35 +/- 0.09, p < 0.03, respectively) and creatine kinase-MB (U/l) at 6 and 12 hours (22.5 +/- 1.5 vs. 40.6 +/- 3.3, p < 0.0001; 23.3 +/- 3.4 vs. 40.8 +/- 8.0, p < 0.001, respectively). Creatine kinase-MB at 24 hours tended to lower values in the MECC group but did not quite reach statistical significance. The MECC system may not only provide a less invasive solution to meet the requirements during cardiac surgery but also a more organ-preserving alternative to standard CPB.

Circulating endothelial cells demonstrate an attenuation of endothelial damage by minimizing the extracorporeal circulation.

OBJECTIVE: Detachment of endothelial cells may represent serious injury of the endothelium after cardiopulmonary bypass. We investigated whether the extent of endothelial injury is related to the type of cardiopulmonary bypass system used (conventional or minimized) and determined circulating endothelial cells as well as von Willebrand factor and soluble thrombomodulin. METHODS: Twenty patients scheduled for elective coronary bypass grafting were randomly assigned to either the minimal extracorporeal circulation system or the standard cardiopulmonary bypass. Ten healthy volunteers served as controls. Circulating endothelial cells per milliliter of full blood were perioperatively determined by immunomagnetic cell separation technique. Endothelial plasma markers were measured by enzyme-linked immunosorbent assay. RESULTS: Preoperative circulating endothelial cell numbers did not differ between the experimental groups, but were significantly higher than in the healthy controls (18.6 +/- 5.6 vs 7.2 +/- 3.8, P < .001). At 6 hours, circulating endothelial cell numbers increased significantly compared with baseline in both experimental groups and peaked at 12 hours after cardiopulmonary bypass initiation, each time with significantly lower values in the minimal extracorporeal circulation group (6 hours: 44.0 +/- 9.9 vs 29.6 +/- 9.8, P = .007; 12 hours: 48.1 +/- 6.8 vs 31.8 +/- 7.1, P < .001). Likewise, von Willebrand factor and soluble thrombomodulin postoperatively increased in both groups with a tendency toward lower levels in the minimal extracorporeal circulation group. Although circulating endothelial cells gradually declined, continually with lower numbers in the minimal extracorporeal circulation group, the endothelial plasma markers remained elevated during observation time. CONCLUSIONS: Circulating endothelial cells represent a novel marker of the intrinsic endothelial damage caused by cardiopulmonary bypass. Its analysis facilitates the evaluation of cardiopulmonary bypass modifications as the minimal extracorporeal circulation system could be proven to be less injurious to endothelium and myocardium.

Pericardial suction blood separation attenuates inflammatory response and hemolysis after cardiopulmonary bypass.

OBJECTIVES: Retransfusion of pericardial suction blood (PSB) is critically considered under the aspect of the biocompatibility of the cardiopulmonary bypass (CPB). We investigated various indicators of inflammation and blood cell activation associated with CPB and re-transfusion of PSB during cardiac surgery. DESIGN: Thirty-five patients undergoing elective coronary artery bypass grafting were prospectively randomized into two groups. In group A (n = 15, retransfusion group) the pericardial suction blood was continuously retransfused during CPB, in group B (n = 20, no-retransfusion group) the suction blood was separated. Parameters indicating the status of the inflammation and blood cell activation were analyzed before and at the end of CPB, latest after 90 minutes on CPB. RESULTS: Patients' perioperative data did not differ between groups. The inflammatory markers C-reactive protein, PMN-Elastase and Interleukin-6 increased in both groups after CPB (p < 0.04) with significantly lower values in the no-retransfusion group (p < 0.02). Leukocytes and platelet activation markers beta-Thromboglobulin and soluble P-Selectin also experienced a significant elevation during observation time (p < 0.02) without any difference between the groups. Free hemoglobin and LDH tremendously increased during CPB with lower values in the no-retransfusion group. CONCLUSIONS: Cardiotomy suction is a major cause of hemolysis and contributes significantly to the systemic inflammatory response.

Effects of poly-2-methoxyethylacrylate (PMEA)-coating on CPB circuits.

OBJECTIVES: In this study, the immuno- and neuroprotective effect of a novel cardiopulmonary bypass coating was investigated. DESIGN: Thirty nine patients scheduled for elective coronary artery bypass grafting were randomly assigned to either PMEA-coated (n = 19) or non-coated CPB circuits (n = 20). Pericardial suction blood was separated and retransfused only if needed at the end of operation. Neurocognitive functions were examined preoperatively and 7-10 days postoperatively using a standard neuropsychological test battery. Assuming an inflammatory etiology, the most cogent inflammatory markers were perioperatively analyzed. RESULTS: Postoperatively, patients of the PMEA-coated group performed better in Go/NoGo and Mini-Mental-test than patients of the non-coated group (p < 0.04). Other neurocognitive testing did not reveal significant differences between the groups. Although most inflammatory parameters showed a significant intraindividual increase during or shortly after CPB, there was no difference in inflammatory alteration between the groups. CONCLUSIONS: PMEA-coating of cardiopulmonary bypass surfaces revealed some minor benefits in preservation of neurocognitive functions after surgery. The immediate inflammatory response remained mostly unaffected. Suction blood separation may additionally contribute to proper postoperative outcome.