Endothelial dysfunction following coronary artery bypass grafting : Influence of patient and procedural factors.

BACKGROUND: Angiopoietin-2 (Angpt2) mediates endothelial dysfunction (ED) following coronary artery bypass grafting (CABG). Its triggers are, however, poorly understood. METHODS: We examined the time course of ED beyond the early phase of postoperative recovery in 75 patients following CABG with a special focus on different cardiopulmonary bypass (CPB) modes as potential triggers of Angpt2 release. RESULTS: Nine patients (12.0%) underwent off-pump coronary artery bypass (OPCAB), 31 patients (41.3%) received minimized extracorporeal circulation (MECC), and 35 patients (46.6%) were operated on with (conventional) CPB. Angpt2 levels steadily increased across the observation period (1.7 [1.4-2.1] to 3.4 [2.5-6.1] ng/ml, p < 0.001). Angpt2 levels did not differ between the MECC and CPB groups (p = 0.564). There was no difference between MECC and CPB patients regarding net fluid balance (p = 0.821) and other surrogate markers of postoperative ED. The magnitude of Angpt-2 increase correlated more strongly with baseline C­reactive protein (r = 0.459, p < 0.001) than with any other parameter. Hospital length of stay correlated more strongly with baseline Angpt2 levels (r = 0.512, p = 0.005) than with follow-up Angpt2 levels and appeared not to be influenced by CPB mode (p = 0.428). CONCLUSION: CABG is associated with prolonged ED, which is determined by the patient's preoperative inflammatory state rather than by CPB modifications.

Predictive value of ScvO2 monitoring for pericardial tamponade after cardiac surgery.

BACKGROUND: We examined the predictive value of central venous oxygen saturation (ScvO2) changes regarding the occurrence of pericardial tamponade following cardiac surgery. METHODS: We retrospectively identified 66 consecutive patients in whom ScvO2 and arterial lactate levels were analyzed during an 8­h time interval preceding pericardiotomy due to pericardial tamponade (PT), and at equivalent time points in 30 control patients (C) who had an uncomplicated course. RESULTS: The median age of the patients was 74 years (interquartile range, 63-78). Three percent of procedures were re-operations. There were no differences between the baseline values of PT and C patients. Pericardiotomy was performed on average 1 day (0-3.5) after cardiac surgery. PT patients displayed a significant decline (p < 0.001) to lower ScvO2 levels (p < 0.001) and a significant increase (p = 0.005) to higher arterial lactate levels (p = 0.019) during the 8 h preceding pericardiotomy, whereas C patients did not (p = 0.440 and p = 0.279, respectively). PT was associated with a longer hospital stay (p = 0.04) and a higher in-hospital mortality (p = 0.008). An ScvO2 decline below 60% (p = 0.018), a delta ScvO2 decline greater than 5% (p = 0.001), and a delta lactate increase greater than 0.18 mmol/l (p = 0.002) during the 8 h preceding pericardiotomy were independently associated with PT. None of these parameters predicted in-hospital mortality. CONCLUSION: Deteriorations in ScvO2 might serve as an early marker of PT following cardiac surgery.

Prolonged Mechanical Ventilation After Lung Transplantation-A Single-Center Study.

This single-center study examines the incidence, etiology, and outcomes associated with prolonged mechanical ventilation (PMV), defined as time to definite spontaneous ventilation >21 days after double lung transplantation (LTx). A total of 690 LTx recipients between January 2005 and December 2012 were analyzed. PMV was necessary in 95 (13.8%) patients with decreasing incidence during the observation period (p < 0.001). Independent predictors of PMV were renal replacement therapy (odds ratio [OR] 11.13 [95% CI, 5.82-21.29], p < 0.001), anastomotic dehiscence (OR 8.74 [95% CI 2.42-31.58], p = 0.001), autoimmune comorbidity (OR 5.52 [95% CI 1.86-16.41], p = 0.002), and postoperative neurologic complications (OR 5.03 [95% CI 1.98-12.81], p = 0.001), among others. Overall 1-year survival was 86.0% (90.4% for LTx between 2010 and 2012); it was 60.7% after PMV and 90.0% in controls (p < 0.001). Conditional long-term outcome among hospital survivors, however, did not differ between the groups (p = 0.78). Multivariate analysis identified renal replacement therapy (hazard ratio [HR] 3.55 [95% CI 2.40-5.25], p < 0.001), post-LTx extracorporeal membrane oxygenation (HR 3.47 [95% CI 2.06-5.83], p < 0.001), and prolonged inotropic support (HR 1.95 [95% CI 1.39-2.75], p < 0.001), among others, as independent predictors of mortality. In conclusion, PMV complicated 14% of LTx procedures and, although associated with increased in-hospital mortality, outcomes among patients surviving to hospital discharge were unaffected.

Gender differences in patient receiving liver transplantation for viral hepatitis.

INTRODUCTION: The course of viral hepatitis shows wide interindividual differences, ranging from asymptomatic disease to liver failure. Only limited data on gender differences in patients undergoing liver transplantation (OLT) exist. We studied the gender distribution in patients who underwent liver transplantation for viral hepatitis. METHODS: A retrospective analysis was performed on a cohort of 368 patients who underwent OLT for viral hepatitis-associated acute or chronic liver failure. In 96 of them, additional hepatocellular carcinoma (HCC) was present at transplantation. Gender ratios of the different hepatitis virus infections and in relation to HCC were evaluated. RESULTS: Significantly more males than females underwent OLT for chronic HBV. In contrast, patients after OLT for fulminant HBV were more frequently females. In patients transplanted for chronic HCV or HDV, no significant gender differences were found. However, men presented more frequently with HCC in both groups of chronic liver disease. CONCLUSIONS: There was a gender difference in HBV infection with more women developing fulminant hepatic failure in acute HBV while more men progressed to end-stage liver disease in chronic HBV. The role of gender in chronic HCV and HDV infection was less pronounced, except for a male predominance among patients with HCC.

[Acute liver failure. How much diagnostic work-up and therapy does my patient need?]. / Akutes Leberversagen. Wie viel Diagnostik und Therapie braucht mein Patient?

Acute liver failure is a multisystem disease with predominantly sudden and severe hepatic injury and hepatic encephalopathy caused by apoptotic or necrotic hepatocyte damage. The clinical challenge in patients with acute liver failure is to promptly identify those with poor prognosis and refer them for emergency liver transplantation. This review article highlights the main aspects of decision making in the setting of acute liver failure, summarizes new aspects of its critical care management and gives an overview of sclerosing cholangitis in the critically ill patient, an under-recognized disease entity that can progress to acute liver failure.

Self-expanding metallic stent placement with laryngeal mask in lung transplant recipients.

BACKGROUND: Bronchial stent insertion is a suitable method to treat airway complications. We present our experience with laryngeal mask airway (LMA) for stent insertion in lung transplant (LT) recipients. METHODS: From April 2007 to March 2009, 27 LT recipients underwent insertion of self-expanding nitinol stents to manage airway complications after LT, using LMA for general anesthesia. All procedures were performed with flexible fiberoptic bronchoscopy without fluoroscopy; stent release was visualized with ultrathin bronchoscopes. We followed technical success, safety, improvement of lung function, and clinical symptoms. RESULTS: Forty-one stents were inserted in 27 patients in 32 sessions. The indications for stent insertion were necrotic lesions (7%) and obstructive lesions (90%). Technical success and safety were 94%. Twice, the stent dislocated, requiring replacements. In 91% of patients, postinterventional improvement in graft function (1 minute forced expiratory volume) was >10% after the intervention. Improvement of clinical symptoms was achieved in 94%. The median procedure time was 38 minutes (range, 30-85 minutes). CONCLUSIONS: LMA offered an excellent condition for stent insertion in LT recipients with airway complications. It provided adequate ventilation and safe airway control during the procedure. This technique may serve as alternative to established techniques using fluoroscopy and rigid bronchoscopy.

Extracorporeal membrane oxygenation in nonintubated patients as bridge to lung transplantation.

We report on the use of veno-arterial extracorporeal membrane oxygenation (ECMO) as a bridging strategy to lung transplantation in awake and spontaneously breathing patients. All five patients described in this series presented with cardiopulmonary failure due to pulmonary hypertension with or without concomitant lung disease. ECMO insertion was performed under local anesthesia without sedation and resulted in immediate stabilization of hemodynamics and gas exchange as well as recovery from secondary organ dysfunction. Two patients later required endotracheal intubation because of bleeding complications and both of them eventually died. The other three patients remained awake on ECMO support for 18-35 days until the time of transplantation. These patients were able to breathe spontaneously, to eat and drink, and they received passive and active physiotherapy as well as psychological support. All of them made a full recovery after transplantation, which demonstrates the feasibility of using ECMO support in nonintubated patients with cardiopulmonary failure as a bridging strategy to lung transplantation.

Clearance of chronic HCV infection during acute delta hepatitis.

The course of chronic hepatitis C in acute HDV/HBV superinfection is unknown. Here, we report a patient with chronic hepatitis C who cleared HCV during acute self-limited hepatitis B/D superinfection. Recovery from HCV was associated with the appearance of a strong and multispecific HDV-specific memory CD4+ and CD8+ T cell response - but only weak HCV-specific CD4+ T cell responses. These data suggest that HCV can be cleared by bystander mechanisms during acute infections with other pathogens which may be considered in the development of immunotherapies for hepatitis C.

Pneumococcal meningitis during antiviral treatment with interferon and ribavirin in a splenectomized patient with chronic hepatitis C - do not miss vaccination before starting therapy.

We report on a 35-year-old man who developed pneumococcal meningitis while receiving antiviral therapy with interferon (consensus interferon, CIFN) and ribavirin for chronic hepatitis C. Antibiotic therapy was started four days after the onset of symptoms. Unfortunately, the patient developed a persisting right-sided cochlear hearing impairment. Antiviral therapy led to sustained viral response of hepatitis C. At the age of 14 years he had experienced a hemorrhagic shock after a traffic accident, received multiple blood transfusions and undergone a splenectomy. He had not received vaccination against Streptococcus pneumoniae. This case report reminds us that splenectomized patients without previous pneumococcal vaccination should receive such vaccination before immunomodulatory treatment.

Impaired TRAIL-dependent cytotoxicity of CD1c-positive dendritic cells in chronic hepatitis C virus infection.

Dendritic cells (DCs) play a central role in antiviral immunity. Conflicting data on DC function have been reported for hepatitis C virus (HCV) infection. In addition to antigen presentation and cytokine secretion, a subset of human DCs displays direct cytotoxic activity. It has been suggested that measles virus and human immunodeficiency virus (HIV) may enhance cytotoxicity of DCs potentially leading to apoptosis of activated T cells and subsequent down-regulation of antiviral immune responses. We demonstrate that CD1c-positive myeloid DCs, but not BDCA-4-positive plasmacytoid DCs, are able to kill different target cells mainly via tumour necrosis factor-related apoptosis-inducing ligand. The ability of CD1c+ DCs to lyze target cells was found to be completely impaired in patients with chronic hepatitis C (10 chronic HCV patients vs 10 healthy controls; P < 0.001) but not in patients with primary biliary cirrhosis. Successful antiviral therapy of chronic hepatitis C rescued the cytotoxicity of DCs. Myeloid DCs of HCV patients and healthy controls had a similar phenotype and endocytotic activity, however, the frequency of mDCs in the peripheral blood was lower (P = 0.004) and the allostimulatory function was weaker (P < 0.001) in chronic hepatitis C. Thus, in contrast to HIV and measles virus studies on monocyte-derived DCs, freshly isolated myeloid DCs of patients with hepatitis C do not show an increased but a completely abolished cytotoxic activity. The impaired DC cytotoxicity could represent a novel mechanism for the increased prevalence of autoimmunity in HCV infection.

Making sense of muscle fatigue and liver lesions.

Muscle weakness is a common complaint in clinical practice. If this symptom is combined with focal liver lesions there is a broad spectrum of differential diagnoses for the gastroenterologist to consider. Tumors of neuroendocrine origin such as small-cell lung carcinoma (SCLC) produce a wide array of peptide hormones and are common causes of paraneoplastic syndromes. We report on a 68-year-old woman who presented with progressing muscle fatigue and multiple liver lesions on ultrasonography. Hypertension, hyperglycemia, hypokalemia and metabolic alkalosis prompted consideration of underlying hypercortisolism. Further work-up demonstrated an acute ectopic ACTH syndrome as paraneoplastic manifestation of a small cell lung carcinoma. The woman deteriorated rapidly and finally died from intracranial tumor spread and septic complications. This case stresses the diagnostic and therapeutic difficulties of acute ectopic ACTH syndrome in the setting of SCLC.

Safety and efficacy of lamivudine in patients with severe acute or fulminant hepatitis B, a multicenter experience.

Acute hepatitis B progresses to liver failure with the need of liver transplantation in about 1% of cases. We treated patients with severe acute or fulminant hepatitis B with lamivudine in an attempt to prevent hepatitis B virus (HBV) reinfection after potential liver transplantation. Since September 2000, 17 patients with severe acute or fulminant HBV infection were treated with 100 or 150 mg lamivudine daily once we had evidence for a severe course as indicated by an INR >2.0. These were compared to a historic control from our unit and to external patients. Fourteen of the 17 patients (82.4%) survived with full recovery without liver transplantation. All these 14 individuals cleared HBsAg on lamivudine within less than 6 months. Twelve patients recovered quickly as indicated by a normalized prothrombin time within 1 week while two patients had a more prolonged course. None of the patients showed an adverse event. Three patients requiring transplantation despite lamivudine therapy had more advanced disease on admission, of whom one had additionally ingested paracetamol (acetaminophen) while the second was already HBV-DNA negative by polymerase chain reaction on admission. The lamivudine treated patients had significant higher frequency of survival without liver transplantation 82.4 vs 20% (4/20) in the historic control (P < 0.001). Similar data were derived from external centres using lamivudine (15/20, 75%). Lamivudine is safe in patients with severe acute or fulminant hepatitis B, leading to fast recovery with the potential to prevent liver failure and liver transplantation when administered early enough.

[Hepatitis as a travel disease]. / Hepatitis als Reisekrankheit.

Every year over 50 million people travel from industrialized countries to areas with high prevalence of oral-fecal and sexually transmissible forms of viral hepatitis. The risk of infection with hepatitis A is associated with the standard of living, the length of stay, and the area of destination. Acute hepatitis E is predominantly transmitted in India and other Asian countries. The main risk factors for the acquisition of hepatitis B are sexual promiscuity and unprotected sexual intercourse. This report provides detailed information on the risk of hepatitis in travelers, available vaccination schedules, clinical and laboratory diagnostic features, and necessary therapeutic aspects in cases of ongoing acute viral hepatitis.