Rabies post-exposure prophylaxis in Germany - What are the challenges?

Rabies post-exposure prophylaxis (R-PEP) including wound treatment, vaccination and application of rabies immunoglobulin (RIG) is essential in preventing rabies mortality. Today, Germany is officially declared free from terrestrial rabies and rabies is only found in bats. However, physicians in A&E Departments are frequently consulted on the need for R-PEP. We retrospectively analysed patients who received R-PEP at the A&E Department of the University Hospital Bonn between 01.01.2013 and 30.06.2019. Demographic data, travel history, clinical and laboratory findings, previous rabies vaccinations and R-PEP vaccination regimen were recorded. During the study period, 90 patients received R-PEP at the University Hospital Bonn, in 10 cases without indication for R-PEP. Altogether, we found deviations from R-PEP guidelines in 51% (n = 41/80). Infiltration of RIG was missed in 12 patients and incorrectly administrated in 24 patients. Furthermore, vaccination scheme was incorrect in 11 patients. Correct wound washing and documentation of tetanus status was missing in 14% and 63% of patients, respectively. Despite rabies elimination in Germany patients frequently seek advice for R-PEP, the majority returning from foreign travel. Our data show that there is a high need for education on indication for R-PEP before and after travel and for implementation of precise R-PEP guidelines in daily clinical practice.

[Esophageal variceal bleeding: management and tips on transjugular intrahepatic portosystemic shunt]. / Ösophagusvarizenblutung: Management und Tipps zum transjugulären intrahepatischen portosystemischen Shunt.

BACKGROUND: Esophageal variceal bleeding is a life-threatening complication in patients with liver cirrhosis, which is pathophysiologically explained by the presence of portal hypertension. The incidence of such bleeding greatly depends on the severity of the underlying liver disease. OBJECTIVE: The aim of this article is to present the current treatment concepts for acute esophageal variceal bleeding, the management in acute situations and the indications for treatment of the causal portal hypertension with a transjugular intrahepatic portosystemic shunt (TIPS). RESULTS: In patients with liver cirrhosis or any other disease causing portal hypertension, a staging examination by esophagogastroduodenoscopy is first carried out for determination of the stage of the varices and the resulting necessary treatment. In addition, determination of the portal pressure gradient is useful. In patients with varices a medicinal or endoscopic bleeding prophylaxis should subsequently additionally be initiated. After an acute variceal bleeding event, under clearly defined prerequisites an evaluation for TIPS implantation should be considered. This is the only effective treatment for reducing portal hypertension. CONCLUSION: With appropriate indications implantation of a TIPS is an effective strategy to lower portal hypertension and therefore prevent recurrent variceal bleeding. The resulting improvement of the portal hemodynamics leads to an improvement in kidney function; however, it also leads to deterioration of liver function with subsequent development or deterioration of a previously existing hepatic encephalopathy.

[Treatment approach for gall bladder and extrahepatic bile duct cancer]. / Therapeutisches Vorgehen bei Gallenblasen- und extrahepatischen Gallengangskarzinomen.

BACKGROUND: Although the treatment and diagnostic regimens of gall bladder carcinoma and extrahepatic bile duct cancer have improved over the past years, the outcome and overall survival as prognostic values still remain poor. Early tumor stages of gall bladder carcinoma are the only exception. OBJECTIVE: This article focuses on the latest surgical therapy approaches including neoadjuvant, adjuvant and palliative therapy regimens. RESULTS: Neoadjuvant treatment concepts have so far been insufficiently evaluated and can therefore only be recommended within the framework of studies. In patients with primary resectable tumors there are so far no indications for improved results after neoadjuvant therapy. Radical R0 resection still remains the only curative treatment option; however, an advanced and inoperable stage is often already present at the time of diagnosis There are no uniform adjuvant treatment concepts and no standards evaluated by studies. Due to the currently available data, adjuvant radiochemotherapy and chemotherapy can also only be recommended within or as part of clinical trials. Palliative chemotherapy should only be used in advanced tumor stages and depending on the condition of the patient. CONCLUSION: To sustainably improve treatment strategies for advanced gall bladder carcinoma and extrahepatic bile duct cancer, uniform adjuvant as well as neoadjuvant therapy regimens need to be developed after evaluation in prospective randomized trials. This is the only way to improve the still poor prognosis of these tumor entities.

[Posthepatectomy Liver Failure in Extended Liver Resections: An Overview Based on a Retrospective Single-Centre Analysis]. / Postoperatives Leberversagen nach erweiterten Leberresektionen - eine Übersicht, gestützt durch eine retrospektive Single-Center-Analyse.

BACKGROUND: Posthepatectomy liver failure (PHLF) is one of the most serious complications after major liver resections and an important factor in terms of perioperative morbidity and mortality. Despite many advances in the understanding and grading of PHLF, the definitions found in literature are very heterogeneous, which complicates the identification of high-risk patients. In this study we analysed the results of extended liver resections and potential risk factors for PHLF based on patient data derived from our tertiary referral centre. The aim of the study was to gain an overview of the essential aspects in the prevention of PHLF combined with key intraoperative issues and postoperative treatment strategies. METHODS: We analysed data from 202 patients who underwent extended elective liver resections at our centre between April 1989 and September 2009 (135 right hemihepatectomies, 39 left hemihepatectomies, 28 right trisectionectomies). According to Balzan's "50/50 criteria", PHLF was defined as prothrombin time (PT) < 50 % combined with serum bilirubin (SB) > 50 micromol/L on postoperative day (POD) 5 or as death due to primary or secondary liver failure. RESULTS: Thirty-day mortality and overall in-hospital mortality were 4.95 and 8.91 %, respectively. Twenty-eight (14 %) patients developed PHLF and 16 (57 %) patients died. Compared to patients with normal postoperative liver function, several significant pre- and intraoperative factors for PHLF were identified, e.g. primary malignant liver tumour (p < 0.001), extended liver resection (p < 0.001), time of surgery (p < 0.001) and intraoperative transfusion of packed RBC (p < 0.02) or FFP (p < 0.001). CONCLUSION: Although progress has been made in hepatobiliary surgery, PHLF remains a serious complication, especially after extended liver resections. Careful, optimised preoperative risk stratification is required to identify patients at risk for PHLF.

[Complications after Percutaneous Endoscopic Gastrostomy Tube Placement - A Retrospective Analysis]. / Komplikationen nach Anlage einer perkutanen endoskopischen Gastrostomie - eine retrospektive Analyse.

BACKGROUND: Enteral nutrition is vital for patients with inadequate or absent oral food intake, as it can help to avoid catabolic metabolism. Enteral feeding can be secured by placing a percutaneous endoscopic gastrostomy tube (PEG-tube) which is an approved method. Several clinical studies could verify the superiority of this procedure compared to other options. Even though PEG-tube placement is regarded as less invasive surgery, a considerable rate of complications is reported in literature. MATERIAL/METHODS: Here, we report a retrospective analysis of PEG-tube placements in the Bonn University Hospital from January 2005 to December 2012. RESULTS: Overall, 641 PEG-tubes were placed with a complication rate of 9.4 %, which can be further divided in 5.5 % minor complications (mic) and 3.9 % major complications (mac). Two cases of death occurred in the context of PEG-tube placement. Endoscopically inserted PEG-tubes showed a complication rate of 8.6 % (4.8 % mic, 3.8 % mac). 63.2 % of mac consisted of perforations, 15.8 % of intra-abdominal abscesses and 15.8 % of buried bumper syndromes. The complication rate of CT-guided placement of PEG-tubes was 38.9 % (27.8 % mic, 11.1 % mac). In this group, all mac were perforations. Surgical PEG-tube placement was accompanied by no mac and 7.7 % mic. CONCLUSION: The amount of complications during PEG-tube placement is remarkable, therefore the indication of this procedure must be contemplated critically and careful follow-up is crucial.

Primary perivascular epitheloid cell tumour (PEComa) of the liver: case report and review of the literature.

PURPOSE: Perivascular epitheloid cell tumour [PEComa] is a rare neoplasm entity, characterized by perivascular epitheloid cells with a coexpression of smooth muscle and melanocytic markers. PEComas are found in a variety of localizations, though lesions within the liver are still scarcely found. Although the majority of these tumours are recognized as benign, there are some reports about advanced and aggressive tumours even with fatal outcome. By means of this case report and literary review including other 21 published cases, potential treatment modalities concerning clinical diagnostics, therapy and the follow-up care should be discussed. METHODS: The following report presents the case of a 53-year old woman with a known liver lesion, since four years under regularly sonographic controls. Finally, after a haemorrhage episode, the lesion was resected and the diagnosis found. For the literary review a systematic search for case reports published between January 1, 1999 and May 1, 2012 was performed on Pubmed. RESULTS: The only way, till now, of confirming the diagnosis is through immunohistochemical examinations. The already published Malignancy criteria by Folpe et al. must be taken carefully in question, as there are cases of malignant behaviour, that do not exactly coincide with these. CONCLUSION: Primary PEComa of the liver must be treated as potential malignant and therefore a close follow-up is demanded.

Orthotopic liver transplantation in human-immunodeficiency-virus-positive patients in Germany.

Objectives. This summary evaluates the outcomes of orthotopic liver transplantation (OLT) of HIV-positive patients in Germany. Methods. Retrospective chart analysis of HIV-positive patients, who had been liver-transplanted in Germany between July 1997 and July 2011. Results. 38 transplantations were performed in 32 patients at 9 German transplant centres. The reasons for OLT were end-stage liver disease (ESLD) and/or liver failure due to hepatitis C (HCV) (n = 19), hepatitis B (HBV) (n = 10), multiple viral infections of the liver (n = 2) and Budd-Chiari-Syndrome. In July 2011 19/32 (60%) of the transplanted patients were still alive with a median survival of 61 months (IQR (interquartile range): 41-86 months). 6 patients had died in the early post-transplantation period from septicaemia (n = 4), primary graft dysfunction (n = 1), and intrathoracal hemorrhage (n = 1). Later on 7 patients had died from septicaemia (n = 2), delayed graft failure (n = 2), recurrent HCC (n = 2), and renal failure (n = 1). Recurrent HBV infection was efficiently prevented in 11/12 patients; HCV reinfection occurred in all patients and contributed considerably to the overall mortality. Conclusions. Overall OLT is a feasible approach in HIV-infected patients with acceptable survival rates in Germany. Reinfection with HCV still remains a major clinical challenge in HIV/HCV coinfection after OLT.

[Heterozygous alpha-1-antitrypsin deficiency (PiMZ): risk factor in the development of primary liver carcinoma in non-cirrhotic liver?]. / Heterozygoter Alpha-1-Antitrypsin-Mangel (PiMZ): Risikofaktor zur Entwicklung eines hepatozellulären Karzinoms in der nicht zirrhotischen Leber?

Here we report on a patient with a primary hepatocellular carcinoma in a non-cirrhotic liver, in whom heterozygosity for an AAT-deficiency allele was found (PiMZ). Based on this observation and the current literature, the possible mechanisms for an eventual contribution of a heterozygosity of a heterozygous AAT-deficiency for a hepatocellular carcinoma are discussed. Alpha-1-antitrypsin (AAT)-deficiency (Laurell-Eriksson syndrome) is a genetic disorder, in which individuals who are homozygous for a deficiency allele are at an increased lifetime risk for pulmonary emphysema, liver cirrhosis, and primary hepatocellular carcinoma. It has been controversially discussed whether the heterozygous form (PiMZ) is also associated with an increased risk for liver diseases. Hepatocarcinogenesis for AAT-deficiency is probably based on a series of toxic events. Precipitation of AAT aggregates in hepatocytes is the initial step. These accumulate in the endoplasmic reticulum and cannot be eliminated from all hepatocytes by proteasomal and non-proteasomal mechanisms. AAT aggregates induce proinflammatory pathways and may be a stimulus for hepatocarcinogenesis. This hypothesis is based mostly on studies of individuals homozygous for a deficiency allele (PiZZ). The mechanism may also play a role in heterozygous patients. Since not all patients with precipitates of AAT-aggregates are develop a hepatocellular carcinoma related comorbidities such as chronic hepatitis B, C, chronic alcohol abuse, or so far unknown genetic and environmental factors may be crucial.

Exogenous superoxide dismutase prevents peroxynitrite-induced apoptosis in non-heart-beating donor livers.

OBJECTIVE: To investigate the role of oxygen free radicals in the induction of apoptosis in non-heart-beating donor (NHBD) livers, and if superoxide dismutase (SOD) ameliorates these alterations. METHODS: Rat livers were perfused via the portal vein with histidine/tryptophan/alpha-ketoglutarate solution from heart-beating donors (HBD) or 60-min warm ischemia from NHBD, with or without the addition of SOD. After 24 h, cold storage livers were evaluated by isolated reperfusion. RESULTS: NHBD showed significantly higher enzyme leakage and elevated portal venous pressure (PVP) versus HBD. Bile and total adenine nucleotides (TAN) were significantly decreased. Apoptosis was prominent in sinusoidal lining cells, coupled with strong nitrotyrosine staining (NTR). The concentrations of nitric oxide and lipoperoxides were largely increased. SOD medication reduced hepatic enzyme release by 30% and lipoperoxides by nearly 50%. Apoptosis and NTR were significantly decreased, and PVP was strikingly reduced to normal values. A 3-fold enhancement in bile production and 1.5-fold increase in TAN of the liver tissue were also observed. CONCLUSION: NHBD livers are prone to severe reoxygenation injury promoted by oxygen free radicals, massive nitrite oxide production and peroxynitrite-induced apoptosis within the sinusoids. Antioxidant medication with SOD should be considered as a useful means of preserving NHBD livers.

[Influence of neoadjuvant chemotherapy on liver integrity and ischemic tolerance]. / Der Einfluss neoadjuvanter Chemotherapie auf Leberintegrität und Ischämietoleranz.

The increasing interest in neoadjuvant chemotherapy of liver metastasis after colorectal carcinoma prior to resection has focussed surgical concerns to the influence of oncological chemotherapy on hepatic tolerance to intraoperative ischaemia. The present study was thus undertaken in order to produce first experimental data on liver function and morphology after neoadjuvant chemotherapy and subsequent ischaemic challenge in a rat model. Male Wistar rats were randomised to receive an intraperitoneal chemotherapy (CH) or placebo (PL) according to the same protocol. Afterwards the animals were subjected to 30 min of total hepatic ischaemia induced by Pringle's manoeuvre and subsequent reperfusion for 1 h or 24 h. Serum activities of hepatic enzymes showed no differences between CH and PL at any time. Bile flow, however, was found to be significantly reduced in CH. In contrast, post-ischaemic up-regulation of PUMA and cleavage of caspase3 was found to be more prominent in PL than in CH, while the antiapoptotic chaperone GRP78 revealed a higher expression in the latter. It is concluded that chemotherapy did not affect ischaemic tolerance of the liver in our model, but promoted a kind of preconditioning, that is likely to counteract cellular induction of apoptosis upon ischaemic challenge.

Endoplasmic and vascular surface activation during organ preservation: refining upon the benefits of machine perfusion.

The endoplasmic reticulum (ER) represents a subcellular target reactive to various cytosolic impairments. The involvement of ER-stress in organ preservation was investigated, comparing machine preservation, cold storage (CS) and a novel concept of only temporary perfusion after procurement. Rat livers were retrieved 30 min after cardiac arrest and preserved for 18 h by CS, oxygenated machine perfusion for 18 h (18 h MP) or for 2 h with subsequent CS for 16 h (2 h MP + 16 h CS). Upon reperfusion, 18 h MP significantly improved enzyme leakage (ALT, LDH) and promoted a 2-fold increase of metabolic recovery compared to CS. However, vascular stress, evaluated by endothelin-release, was significantly elevated after 18 h MP. Interestingly, better viability was obtained using the short-term perfusion protocol (2 h MP + 16 h CS), which further reduced enzyme leakage, maintained energetic recovery and mitigated endothelin-release compared to 18 h MP. Caspase 12-mRNA was upregulated in the 18 h MP-group but unchanged after CS or 2 h MP + 16 h CS. Activation/cleavage of caspase 12 protein was significantly enhanced after 18 h MP and very low in the 2 h MP + 16 h CS-group. Correspondingly, electron microscopy showed ultrastructural alterations of ER after CS and especially after 18 h MP but not after 2 h MP + 16 h CS. At this time mitochondrial appearance was unaffected in all groups, suggesting the ER to be an early subcellular target of preservation injury. In our model, ER and vascular endothelium were best protected by only temporary machine perfusion, which also maintained overall graft viability.

Oxygenated machine perfusion preservation of predamaged kidneys with HTK and Belzer machine perfusion solution: an experimental study in pigs.

The objective of the present study was to evaluate the recently proposed aerobic machine preservation with the noncolloidal HTK solution by comparison with the colloidal Belzer machine perfusion solution (MPS) after procurement of marginal kidneys from non-heart-beating donors. Kidneys were harvested 40 minutes after cardiac arrest in German Landrace pigs and subjected to 18 hours of oxygenated hypothermic machine perfusion with either Belzer MPS or modified HTK via the renal artery (Psys < 40 mm Hg). During machine perfusion transrenal flow was approximatively twofold higher and calculated oxygen uptake was increased by 30% using the colloidal Belzer MPS, but overall enzyme release was comparable in both groups. After heterotopic transpantation with bilateral nephrectomy of the recipient, there were no differences with respect to initial tissue perfusion in vivo (evaluated by laser Doppler flowmetry) as well as urine production and median serum levels of urea or creatinine over 1 week of follow-up between grafts perfused with HTK or Belzer MPS. In conclusion, provision of oxygen during storage is possible by low-flow perfusion with HTK as with Belzer MPS.

[Studies on low protein C-expression in severe sepsis]. / Untersuchungen zur verminderten Protein-C-Expression in der schweren Sepsis.

OBJECTIVES: Low concentration of protein C in severe sepsis may be associated with increased morbidity and mortality. The present study was designed to clarify to what extent there are differences in the time course of plasma concentrations of protein C in patients with systemic inflammatory response syndrome or patients with severe sepsis. In addition, the cause of decreased expression of protein C in severe sepsis was examined. METHODS: 32 patients with severe sepsis and 10 patients with systemic inflammatory response syndrome admitted to a surgical intensive care unit were enrolled in the study. While the patients stayed in the intensive care unit protein C plasma concentrations and the clotting factors thrombin-antithrombin-complex and factor VII were determined twice weekly. RESULTS: Comparing patients with severe sepsis and systemic inflammatory response syndrome there was no significant difference concerning plasma levels of protein C, thrombin-antithrombin-complex and factor VII. In contrast, surviving patients with severe sepsis exhibited significant higher protein C levels compared to non-survivors. In addition, significant lower plasma levels of thrombin-antithrombin-complex were determined in survivors compared to non-survivors. However, factor VII displayed no significant group difference. CONCLUSIONS: Surviving patients with severe sepsis exhibited higher plasma concentrations of protein C than patients who died during severe sepsis. The lower plasma concentrations of protein C in non-survivors may be caused by an increased turnover of protein C served as endogenous anticoagulant in sepsis associated activation of coagulation.

[Analysis of vascular complications in intra-venous drug addicts after puncture of femoral vessels]. / Untersuchung von Gefässkomplikationen nach Punktion der Femoralgefässe bei intravenösem Drogenabusus.

BACKGROUND: Intravenous drug abuse is a global social and health care problem. Vascular complications following intravascular inguinal self-injection of addictive drugs are rarely seen. An efficient therapeutic concept is needed because, besides the risk of vascular injuries, infections ranging up to systemic inflammatory response syndrome or sepsis might occur. METHODS: This was a single center retrospective analysis of vascular complications in drug addicts from 1994 to 2002 in an university hospital. A systematic literature review in MEDLINE was performed with the following key words: 1 vascular, 2 complications, 3 drugs, 4 addicts, 5 mycotic aneurysms. RESULTS: 10 patients with a long lasting history of i. v. drug abuse (median: 16.1 years, range: 10-28 years) and vascular complications were included in this study. The mean age was 40.2 years (range 32-50 years). 5 patients showed pain and tumescence of the inguinal region at the time of admission. 7/10 patients had a poor general health and nutritional status. 2 patients had a hepatitis-B- and C-infection, 7 patients were hepatitis C Ag positive. All patients were HIV negative. 1 patient had an older deep venous leg thrombosis that was treated conservatively. In six cases, we saw an intraoperative arterial bleeding; in five cases pseudoaneurysms. The patients were treated with 5 venous interpositions, 4 venous patch plastics, 1 end-to-end anastomosis and 2 prosthetic grafts. 3 thrombectomies were performed. One time we performed a ligation of the pseudoaneurysm without reconstruction. Six reconstructions were covered with a biological seal. One thigh amputation was necessary; no patient died. In 2 patients with severe problems, we performed 11 operative revisions. The systematic literature review in MEDLINE showed no evidenced based therapy regimen. CONCLUSION: We favour the resection of the aneurysm including a radical debridement of the wound with secondary wound healing. In the case of an isolated aneurysm of the arteria femoralis superficialis or the arteria profunda femoris, a ligation or excision without reconstruction is possible with a low risk of postoperative complications. A reconstruction with autologous material is necessary in the case of aneurysms of the common femoral artery or its bifurcation. The reconstructed vessel should be covered with a biological seal, e. g. omentum majus. If there is no autologous material available for the reconstruction, we recommend the ligation without reconstruction, because the results after implantation of artificial vascular prostheses are not satisfying.