Symptomatic lymphoceles after kidney transplantation – multivariate analysis of risk factors and outcome after laparoscopic fenestration

Ulrich F, Niedzwiecki S, Fikatas P, Nebrig M, Schmidt SC, Kohler S, Weiss S, Schumacher G, Pascher A, Reinke P, Tullius SG, Pratschke J. Symptomatic lymphoceles after kidney transplantation – multivariate analysis of risk factors and outcome after laparoscopic fenestration.
Clin Transplant 2009 DOI: 10.1111/j.1399‐0012.2009.01073.x
© 2009 John Wiley & Sons A/S. Abstract: Lymphocele formation is a common complication after kidney transplantation, and laparoscopic surgery has become a widely accepted treatment option. The aim of this retrospective study was to analyze the risk factors of lymphocele development and to assess the treatment outcome after laparoscopic fenestration. We analyzed 426 renal allograft recipients operated between 2002 and 2006 receiving triple immunosuppression with calcineurin inhibitors. The incidence of lymphocele was 9.9%, while 24 (5.6%) patients with symptomatic lymphoceles required laparoscopic surgery. Serum creatinine at diagnosis was significantly higher in patients with lymphoceles treated surgically (3.2 ± 0.7 vs. 1.7 ± 0.6 mg/dL; p < 0.001). After successful laparoscopic intervention, creatinine concentrations recovered until discharge and were comparable to other patients (1.6 ± 0.5 vs. 1.5 ± 0.5 mg/dL; p = NS). While we observed a significant association of lymphocele formation with diabetes, tacrolimus therapy, and acute rejection in univariate testing, only diabetes remained a significant factor after multivariate analysis. Laparoscopic fenestration proved to be a safe and efficient method without any associated mortality and a low recurrence rate of 8.3% (n = 2). We conclude that diabetes is an independent risk factor for lymphocele development, and laparoscopic fenestration should be the treatment of choice for larger and symptomatic lymphoceles, as it is safe and offers a low recurrence rate.     

Deciphering the Role of Extracellular Vesicles Derived from ZIKV-Infected hcMEC/D3 Cells on the Blood–Brain Barrier System

To date, no vaccines or antivirals are available against Zika virus (ZIKV). In addition, the mechanisms underlying ZIKV-associated pathogenesis of the central nervous system (CNS) are largely unexplored. Getting more insight into the cellular pathways that ZIKV recruits to facilitate infection of susceptible cells will be crucial for establishing an effective treatment strategy. In general, cells secrete a number of vesicles, known as extracellular vesicles (EVs), in response to viral infections. These EVs serve as intercellular communicators. Here, we investigated the role of EVs derived from ZIKV-infected human brain microvascular endothelial cells on the blood–brain barrier (BBB) system. We demonstrated that ZIKV-infected EVs (IEVs) can incorporate viral components, including ZIKV RNA, NS1, and E-protein, and further transfer them to several types of CNS cells. Using label-free impedance-based biosensing, we observed that ZIKV and IEVs can temporally disturb the monolayer integrity of BBB-mimicking cells, possibly by inducing structural rearrangements of the adherent protein VE-cadherin (immunofluorescence staining). Finally, differences in the lipidomic profile between EVs and their parental cells possibly suggest a preferential sorting mechanism of specific lipid species into the vesicles. To conclude, these data suggest that IEVs could be postulated as vehicles (Trojan horse) for ZIKV transmission via the BBB.     

Multicentric evaluation of model for end‐stage liver disease‐based allocation and survival after liver transplantation in Germany – limitations of the ‘sickest first’‐concept

Since the introduction of model for end‐stage liver disease (MELD) in 2006, post‐orthotopic liver transplantation (OLT) survival in Germany has declined. The aim of this study was to evaluate risk factors and prognostic scores for outcome. All adult OLT recipients in seven German transplant centers after MELD implementation (December 2006–December 2007) were included. Recipient data were analyzed for their influence on 1‐year outcome. A total of 462 patients (mean calculated MELD = 20.5, follow‐up: 1 year) were transplanted for alcoholic cirrhosis (33.1%), hepatocellular carcinoma (26.6%), Hepatitis‐C (17.1%), Hepatitis‐B (9.5%), primary sclerosing cholangitis (5.6%) and late graft‐failure after first OLT before December 2006 (8.7%). 1‐year patient survival was 75.8% (graft survival 71.2%) correlating with MELD parameters and serum choline esterase. MELD score >30 [odds ratio (OR) = 4.17, confidence interval: 2.57–6.78, 12‐month survival = 52.6%, c‐statistic = 0.669], hyponatremia (OR = 2.07), and pre‐OLT hemodialysis (OR = 2.35) were the main death risk factors. In alcoholic cirrhosis (n = 153, mean MELD = 21.1) and hepatocellular carcinoma (n = 123, mean MELD = 13.5), serum bilirubin and the survival after liver transplantation score were independent outcome parameters, respectively. MELD >30 currently represents a major risk factor for outcome. Risk factors differ in individual patient subgroups. In the current German practice of organ allocation to sicker patients, outcome prediction should be considered to prevent results below acceptable standards.     

Postoperative Immunosuppression After Open and Laparoscopic Liver Resection: Assessment of Cellular Immune Function and Monocytic HLA-DR Expression

Background and Objectives:

Major abdominal procedures are strongly associated with postoperative immunosuppression and subsequent increased patient morbidity. It is believed that laparoscopic surgery causes less depletion of the systemic immune function because of the reduced tissue trauma. Various cytokines and monocytic HLA-DR expression have been successfully implemented to assess postoperative immune function. The aim of our study was to show the difference in immunologic profiles after minimally invasive versus conventional liver resection.

Methods:

Ten animals underwent either laparoscopic or conventional open left lateral liver resection. Flow cytometric characteristics of HLA-DR expression on monocytes and lipopolysaccharide-stimulated cellular secretion of tumor necrosis factor α, interferon γ, interleukin 6, and interleukin 8 were measured and analyzed in ex vivo whole blood samples. Intraoperative and postoperative clinical outcome parameters were also documented and evaluated.

Results:

All animals survived the procedures. Postoperative complications were fever (n = 3), wound infections (n = 2), and biloma (n = 1). Open surgery showed a morbidity rate of 80% compared with 40% after laparoscopic surgery. Laparoscopic liver resection showed no postoperative immunoparalysis. Major histocompatibility complex class II expression in this group was elevated, whereas the open surgery group showed decreased major histocompatibility complex class II expression on postoperative day 1. Postoperative secretion of tumor necrosis factor α, interleukin 6, and interferon γ was lower in the open surgery group. Elevated transaminase levels after laparoscopy might have resulted from an ischemia/reperfusion injury caused by the capnoperitoneum.

Conclusion:

Major immunoparalysis depression was not observed in either group. Laparoscopic surgery shows a tendency to improve immunologic recovery after liver resection.     

Cost analysis of inguinal hernia repair: the influence of clinical and hernia-specific factors

Introduction

As in the rest of the world, in Germany, inguinal hernia operations are among the most common operations. From an economic standpoint, very little is known about the influence of demographic, clinical or hernia-related parameters on the cost of inguinal hernia repair. We, therefore, evaluated individual patient parameters associated with higher costs with a special focus on multimorbidity.

Methods

A total of 916 patients underwent hernia repair for primary or recurrent inguinal hernia between 2014 and 2017 at a single university center and were included in the analysis. The clinical and financial data of these patients were analyzed to identify cost-increasing parameters.

Results

A majority of patients were male (90.7%), with a mean age of 55 years. The surgical methods utilized were mainly the TAPP (57.2%) and Lichtenstein (41.7%) procedures, with an average duration of surgery of 85 min and an average duration of anesthesia of 155 min. The mean cost of all procedures was 3338.3 € (±?1608.1 €).

Older age, multimorbidity, emergency operations with signs of incarceration, longer hospital stays and postoperative complications were significant cost-driving factors. On the other hand, sex, the side of the hernia (left vs. right) and the presence of recurrent hernias had no influence on the overall direct costs.

Conclusion

From a purely economic point of view, older age and multimorbidity are demographic cost-driving factors that cannot be influenced. The national hospital reimbursement system needs to consider and compensate for these factors. Emergency operations need to be prevented by early elective treatment. Long postoperative stays and postoperative complications need to be prevented by proper preoperative check-ups and accurate treatment.

     

Single Pass Albumin Dialysis—A Dose‐Finding Study to Define Optimal Albumin Concentration and Dialysate Flow

Several artificial liver support concepts have been evaluated both in vitro and clinically. Single pass albumin dialysis (SPAD) has shown to be one of the most simple approaches for removing albumin‐bound toxins and water‐soluble substances. Being faced with acute liver failure (ALF) in everyday practice encouraged our attempt to define the optimal conditions for SPAD more precisely in a standardized experimental setup. Albumin concentration was adjusted to either 1%, 2%, 3%, or 4%, while the flow rate of the dialysate was kept constant at a speed of 700 mL/h. The flow rate of the dialysate was altered between 350, 500, 700, and 1000 mL/h, whereas the albumin concentration was continuously kept at 3%. This study revealed that the detoxification of albumin‐bound substances could be improved by increasing the concentration of albumin in the dialysate with an optimum at 3%. A further increase of the albumin concentration to 4% did not lead to a significant increase in detoxification. Furthermore, we observed a gradual increase of the detoxification efficiency for albumin‐bound substances, from 350 mL/h to 700 mL/h (for bilirubin) or 1000 mL/h (for bile acids) of dialysate flow. Water‐soluble toxins (ammonia, creatinine, urea, uric acid) were removed almost completely, regardless of albumin concentration or flow rate. In conclusion, this study confirmed that SPAD is effective in eliminating albumin‐bound as well as water‐soluble toxins using a simulation of ALF. Furthermore, this project was successful in evaluating the most effective combination of albumin concentration (3%) and dialysate flow (700 mL/h–1000 mL/h) in SPAD for the first time.