Cross-specificity of protective human antibodies against Klebsiella pneumoniae LPS O-antigen.

Humoral immune responses to microbial polysaccharide surface antigens can prevent bacterial infection but are typically strain specific and fail to mediate broad protection against different serotypes. Here we describe a panel of affinity-matured monoclonal human antibodies from peripheral blood immunoglobulin M-positive (IgM+) and IgA+ memory B cells and clonally related intestinal plasmablasts, directed against the lipopolysaccharide (LPS) O-antigen of Klebsiella pneumoniae, an opportunistic pathogen and major cause of antibiotic-resistant nosocomial infections. The antibodies showed distinct patterns of in vivo cross-specificity and protection against different clinically relevant K. pneumoniae serotypes. However, cross-specificity was not limited to K. pneumoniae, as K. pneumoniae-specific antibodies recognized diverse intestinal microbes and neutralized not only K. pneumoniae LPS but also non-K. pneumoniae LPS. Our data suggest that the recognition of minimal glycan epitopes abundantly expressed on microbial surfaces might serve as an efficient humoral immunological mechanism to control invading pathogens and the large diversity of the human microbiota with a limited set of cross-specific antibodies.

Impact of microvessel density on lymph node metastasis and survival after curative resection of pancreatic cancer.

PURPOSE: The roles of angiogenesis and the most prominent angiogenic vascular endothelial growth factor (VEGF) in diseases of the pancreas remain controversial. We compared microvessel density (MVD) and VEGF status in normal pancreatic, chronic pancreatic, and pancreatic cancer (PC) tissues to establish their prognostic relevance. METHODS: Eighty samples of PC tissue, 32 samples of normal pancreatic tissue, and 20 samples of chronic pancreatitis (cP) tissue were immunostained with monoclonal anti-CD31 and polyclonal anti-VEGF antibody. The MVD was correlated with clinicopathological features and survival. RESULTS: Microvessel density was higher in PC than in cP (P < 0.001). Residual tumor status was highly predictive for survival (P < 0.001). After stratification for residual tumor status, we identified lymph node metastasis (LNM) in more than two lymph nodes (P < 0.04) and high MVD (P < 0.03) as risk factors for mortality. Multivariate analysis revealed only a high MVD (P = 0.03, odds ratio 0.441, 95% confidence interval 0.211-0.821) as an independent predictor of poor survival. Vascular endothelial growth factor was found over stromal cells in cP and over ductal adenocarcinoma cells in PC. Vascular endothelial growth factor expression status was not predictive of survival (P < 0.07). CONCLUSION: This study confirms the role of angiogenesis in PC and identifies MVD as an independent prognostic factor in patients with curatively resected PC.

Balanced management of hepatic trauma is associated with low liver-related mortality.

BACKGROUND: Hepatic trauma is a rare surgical emergency with significant morbidity and mortality. Therapeutic strategies have been controversially discussed during the last decades. METHODS: The medical records of 47 consecutive patients with hepatic trauma treated at the University Hospital of Leipzig between 2004 and 2008 were retrospectively reviewed for the severity of liver injury, management, morbidity, and mortality and compared to a preceding cohort. Logistic regression analysis was performed to identify risk factors influencing mortality. RESULTS: Compared to 63 patients treated between 1993 and 2003, moderate liver injuries (grades I-III) occurred more frequently (p = 0.0006), and the proportion of patients that were managed operatively decreased from 68.9% to 37.5%. Twenty patients (42.6%) were treated conservatively (all grades I to III) and 27 surgically (47.4%). In detail, five patients were treated by hepatic packing alone, 13 by suture or coagulation, five by atypical resection, and four by hemihepatectomy. The overall mortality was 8.5% with a liver-related mortality rate of 2.1%. According to severity grades I-III, IV, and V, mortality rates were 0%, 18.2%, and 50.0%, respectively. Univariate analysis identified Injury Severity Score (ISS) >30, Moore grades IV and V, hemoglobin at admission <6.0 mmol/L, and need for transfusion of >12 erythrocyte concentrates to be significant risk factors for early posttraumatic death, while multivariate analysis only ISS >30 revealed to be of prognostic significance for early postoperative survival. CONCLUSION: Compared to a previous cohort in the same hospital, more patients were treated conservatively. Management of liver injuries presented with a low liver-related mortality rate. Grades I-III injuries can safely be treated by conservative means with excellent results. However, complex hepatic injuries may often require surgical treatment ranging from packing to complex hemihepatectomy. Hence, for selection of appropriate therapeutic options, patients with hepatic injuries should be treated in a specialized institution.

Transplantation of monocyte-derived hepatocyte-like cells (NeoHeps) improves survival in a model of acute liver failure.

OBJECTIVE: Investigation of the efficacy of implantation of monocyte-derived hepatocyte-like cells (NeoHeps) in acute liver failure. SUMMARY BACKGROUND DATA: Extended liver resection or split liver transplantation is still associated with high morbidity and mortality because of postoperative liver insufficiency. In view of liver support systems, implantation of isolated hepatocytes or hepatocyte-like cells such as NeoHeps is increasingly under discussion. METHODS: Twenty-four hours before subtotal hepatectomy, cells of different origin [A: human mononuclear cells (24 x 10(6)); B: NeoHeps (16 x 10(6)); C: NeoHeps (24 x 10(6)); D: rat hepatocytes (24 x 10(6))] were injected into the spleen of Wistar rats. After an observation period of 5 days, animal survival, postoperative weight, and signs of encephalopathy were recorded. At the end of the observation period, blood was collected for laboratory analysis. RESULTS: Transplantation of both rat hepatocytes and NeoHeps significantly improved animal survival when compared with control animals (group A: 21%), reaching 72% in group D (P = 0.001), 50% in group C (P = 0.04), and 36% in group B (P = 0.22). Moreover, animals in these groups postoperatively experienced less frequently signs of encephalopathy, as well as earlier weight increase when compared with group A. DISCUSSION: Hepatocyte transplantation is a practicable and successful treatment option in case of liver insufficiency because implantation of NeoHeps or primary rat hepatocytes had an improving effect on survival. The promising data of the present study warrants further analysis to elucidate the role of NeoHeps in treatment of acute postoperative liver failure to a greater extent.

Adult jejunojejunal intussusception caused by metastasized pleomorphic carcinoma of the lung: report of a case.

Adult small-intestinal intussusception is rare and very different from childhood intussusception. Both benign and malignant pathologies can underlie small intestinal intussusception in adults, but malignancy is much less frequent. We report a case of jejunojejunal intussusception caused by an intestinal metastasis of the sarcomatoid component of pleomorphic carcinoma of the right lung. The patient, a 61-year-old man, underwent successful segmental jejunal resection. Adult small bowel intussusception, though an unusual cause of acute abdomen, requires early diagnosis and timely management. To our knowledge, this is the first report of adult jejunojejunal double intussusception caused by metastatic sarcomatoid carcinoma of the lung.

Segmental intrahepatic cholestasis as a technical complication of the transjugular intrahepatic porto-systemic shunt.

BACKGROUND: Segmental intrahepatic cholestasis caused by transjugular intrahepatic portosystemic shunt (TIPS) (SIC-T), is a rare complication of this technique and only referred by case reports. Thus, we conducted a systematic, retrospective analysis to provide evidence regarding prevalence and consequences of this TIPS-induced bile duct compression. AIM: To assess prevalence and outcome of SIC-T in a large TIPS-cohort. METHODS: In this retrospective cohort study, we screened the institutional databases for all consecutive patients that were treated by TIPS-placement or TIPS-revision between January 2005 and August 2013. We analyzed radiologic images for signs of biliary congestion. Cases that were indicative of SIC-T were reviewed by two independent radiologists and additional patient data was collected. Descriptive statistics of patient demographics, indications for TIPS and procedural details were registered. Logistic regression analysis was performed to identify predictors for the development of SIC-T. RESULTS: We analyzed 135 cirrhotic patients who underwent TIPS (mean age 55 years, 79% male gender). Etiology of cirrhosis was alcohol in most cases and indications for TIPS were mainly refractory ascites and recurrent variceal bleeding. TIPS revision was necessary in 31 patients. We identified 4 cases (2.9%) of SIC-T in direct proximity of the TIPS-stent. Diagnosis was confirmed by CT-scan, MRI or endoscopic retrograde cholangio pancreaticography (ERCP). In two patients TIPS was implanted via the right and in one through the medial hepatic vein. One patient received TIPS-prolongation by multiple revisions. Most patients were asymptomatic but one cholangitic abscess necessitated a transhepatic drain. Logistic regression analysis identified TIPS-placement other than from medial hepatic vein to right portal vein as risk factor (OR 21.0) for SIC-T. CONCLUSION: SIC-T ads to (mostly late) complications in the interventional treatment of cirrhotic portal hypertensions and can lead to cholangitic abscesses. Patients, particularly with multiple interventions, should be screened for SIC-T.

Successful liver transplantation with continued dual antiplatelet therapy.

BACKGROUND: Liver transplantation in patients with dual antiplatelet therapy is considered high-risk procedure due to possible bleeding complications. However, withdrawal of antiplatelet therapy can lead to major adverse cardiac events such as stent thrombosis and even fatal myocardial infarction. CASE REPORT: We report on a 61-year-old male patient with nutritive toxic liver cirrhosis who underwent liver transplantation at our hospital in March 2010. Following two strokes he received secondary prophylaxis with aspirin and clopidogrel, which was continued at time of liver transplantation. The transplantation was performed successfully without withdrawal of the antiplatelet therapy. No cardiac event and no major bleeding complication occurred. CONCLUSIONS: This is, to our knowledge, the first report of a liver transplantation under dual antiplatelet therapy with aspirin and clopidogrel. It shows that even major procedures such as liver transplantation, with its associated high risk of surgical bleeding, can be safely performed with an appropriate risk.

Subcutaneous administration of epidermal growth factor: a true treatment option in case of postoperative liver failure?

Adequate hepatocyte regeneration is mandatory for successful recovery after liver resection. The role of epidermal growth factor (EGF), by subcutaneous injection as a simple route, has not been clearly elucidated yet. Wistar rats underwent 70 or 90% hepatectomy, respectively, and were treated with EGF at day 2 and 3 or served as non-EGF-treated controls. Postoperatively, proliferative parameters (weight of liver remnants, number of mitotic and Ki-67 positive cells, expression of cyclin D1 protein) were evaluated. After 90% hepatectomy, 5 day survival was recorded following EGF treatment using different dosages. A significant increase of hepatocellular proliferation was observed after 70% hepatectomy. However, survival following 90% hepatectomy was not as positively affected, irrespective of EGF dosage, with most animals dead before EGF application was completed. Subcutaneous EGF injection can augment postoperative liver regeneration, however, it might be used only as a prophylactic and not as a therapeutic drug in case of liver insufficiency.