Structured diabetes self-management education and its association with perceived diabetes knowledge, information, and disease distress: Results of a nationwide population-based study.

OBJECTIVE: To evaluate, how participation in structured diabetes self-management education (DSME) programs is associated with perceived level of knowledge about diabetes, information needs, information sources and disease distress. METHODS: We included 796 ever- and 277 never-DSME participants of the population-based survey "Disease knowledge and information needs - Diabetes mellitus (2017)" from Germany. Data on perceived level of diabetes knowledge (12 items), information needs (11 items), information sources (13 items) and disease distress (2 indices) were collected. Multiple logistic regression analyses were used to examine the association of DSME-participation with these outcomes. RESULTS: DSME-participants showed a higher level of diabetes knowledge compared to never-DSME participants, particularly in aspects concerning diabetes in general (odds ratio 2.53; 95% confidence intervals 1.48-4.33), treatment (2.41; 1.36-4.26), acute complications (1.91; 1.07-3.41) and diabetes in everyday life (1.83; 1.04-3.22). DSME-participants showed higher information needs regarding late complications (1.51; 1.04-2.18) and acute complications (1.71; 1.71-2.48) than DSME never participants. DSME-participants more frequently consulted diabetologists (5.54; 3.56-8.60) and diabetes care specialists (5.62; 3.61-8.75) as information sources. DSME participation was not associated with disease distress. CONCLUSION: DSME is a valuable tool for improving individual knowledge about diabetes. However, DSME should focus more on psychosocial aspects to reduce the disease burden.

[Procurement of abdominal organs]. / Abdominale Organentnahme.

Solid organ transplantation is frequently carried out in this society. Under these circumstances the basic principles are altruistic organ donation and abidance by the law, which are regulated by the German Transplantation Act and by directives of the Federal Medical Council from which process instructions of the German Organ Transplantation Foundation are derived. The organ allocation is carried out by the Eurotransplant International Foundation (ET) located in Leiden, the Netherlands. Organ procurement is an essential component of the process of organ donation. This article highlights the procedure for harvesting of abdominal organs and also nonsurgical issues in the process of organ donation.

Social touch during development: Long-term effects on brain and behavior.

In this paper, our goal is to explore what is known about the role of social touch during development. We first address the neural substrates of social touch and the role of tactile experience in neural development. We discuss natural variation in early exposure to social touch, followed by a discussion on experimental manipulations of social touch during development and "natural experiments", such as early institutionalization. We then consider the role of other developmental and experiential variables that predict social touch in adults. Throughout, we propose and consider new theoretical models of the role of social touch during development on later behavior and neurobiology.

Seroepidemiological Studies of Arboviruses in Africa.

The literature on sero-epidemiological studies of flaviviral infections in the African continent is quite scarce. Much of the viral epidemiology studies have been focussing on diseases such as HIV/AIDS because of their sheer magnitude and impact on the lives of people in the various affected countries. Increasingly disease outbreaks caused by arboviruses such as the recent cases of chikungunya virus, dengue virus and yellow fever virus have prompted renewed interest in studying these viruses. International agencies from the US, several EU nations and China are starting to build collaborations to build capacity in many African countries together with established institutions to conduct these studies. The Tofo Advanced Study Week (TASW) was established to bring the best scientists from the world to the tiny seaside town of Praia do Tofo to rub shoulders with African virologists and discuss cutting-edge science and listen to the work of researchers in the field. In 2015 the 1st TASW focussed on Ebola virus. The collections of abstracts from participants at the 2nd TASW which focused on Dengue and Zika virus as well as presentations on other arboviruses are collated in this chapter.

Dengue Virus Envelope Dimer Epitope Monoclonal Antibodies Isolated from Dengue Patients Are Protective against Zika Virus.

UNLABELLED: Zika virus (ZIKV) is a mosquito-borne flavivirus responsible for thousands of cases of severe fetal malformations and neurological disease since its introduction to Brazil in 2013. Antibodies to flaviviruses can be protective, resulting in lifelong immunity to reinfection by homologous virus. However, cross-reactive antibodies can complicate flavivirus diagnostics and promote more severe disease, as noted after serial dengue virus (DENV) infections. The endemic circulation of DENV in South America and elsewhere raises concerns that preexisting flavivirus immunity may modulate ZIKV disease and transmission potential. Here, we report on the ability of human monoclonal antibodies and immune sera derived from dengue patients to neutralize contemporary epidemic ZIKV strains. We demonstrate that a class of human monoclonal antibodies isolated from DENV patients neutralizes ZIKV in cell culture and is protective in a lethal murine model. We also tested a large panel of convalescent-phase immune sera from humans exposed to primary and repeat DENV infection. Although ZIKV is most closely related to DENV compared to other human-pathogenic flaviviruses, most DENV immune sera (73%) failed to neutralize ZIKV, while others had low (50% effective concentration [EC50], <1:100 serum dilution; 18%) or moderate to high (EC50, >1:100 serum dilution; 9%) levels of cross-neutralizing antibodies. Our results establish that ZIKV and DENV share epitopes that are targeted by neutralizing, protective human antibodies. The availability of potently neutralizing human monoclonal antibodies provides an immunotherapeutic approach to control life-threatening ZIKV infection and also points to the possibility of repurposing DENV vaccines to induce cross-protective immunity to ZIKV. IMPORTANCE: ZIKV is an emerging arbovirus that has been associated with severe neurological birth defects and fetal loss in pregnant women and Guillain-Barré syndrome in adults. Currently, there is no vaccine or therapeutic for ZIKV. The identification of a class of antibodies (envelope dimer epitope 1 [EDE1]) that potently neutralizes ZIKV in addition to all four DENV serotypes points to a potential immunotherapeutic to combat ZIKV. This is especially salient given the precedent of antibody therapy to treat pregnant women infected with other viruses associated with microcephaly, such as cytomegalovirus and rubella virus. Furthermore, the identification of a functionally conserved epitope between ZIKV and DENV raises the possibility that a vaccine may be able to elicit neutralizing antibodies against both viruses.

[Gender-Specific Differences in Liver Transplantation]. / Genderspezifische Unterschiede im Rahmen der Lebertransplantation.

Liver transplantation is the treatment of choice for acute hepatic failure or endstage liver disease. Long-time outcome following liver transplantation has been increased as a result of improvements in surgical technique, perioperative management, organ procurement and immunuosuppression. Differences in liver disease, access and allocation to liver transplantation as outcome due to gender have been reported. This review highlights the important differences in the field of liver transplantation.

Tacrolimus effects and side effects after liver transplantation: is there a difference between immediate and extended release?

BACKGROUND: Immunosuppressive therapy after orthotopic liver transplantation (OLT) requires a high degree of patient compliance to guarantee safety and avoid side effects. In 2007, prolonged-release tacrolimus was launched in Europe to improve compliance. In this prospective observational crossover single-center trial, we analyzed effects and side effects of prolonged-release tacrolimus in OLT patients. METHODS: LT patients at our center were included if they were older than l8 years of age, had had the procedure at least 6 months prior, and were outpatients currently on twice-daily tacrolimus. Patients were observed for 6 months before switching to once-daily tacrolimus. Patient history, clinical examination, and laboratory examinations were recorded on inclusion as well as after 3, 6, 9, 12, and 18 months. RESULTS: The rates of rejection, hypertension, hypercholesterolemia, and diabetes mellitus were compared during twice-daily and once-daily tacrolimus. Similarly, laboratory parameters were identical during both periods with the exception of glycated hemoglobin, which was significantly elevated under once-daily tacrolimus (P = .00l). CONCLUSION: Converting patients to extended-release tacrolimus with was safe in terms of rejection, hypertension, and hypercholesterolemia as well as renal and liver functions. Further investigations concerning pharmacokinetics and glucose metabolism will be needed to evaluate prolonged-release tacrolimus.

Comparison of resection and transarterial chemoembolisation in the treatment of advanced intrahepatic cholangiocarcinoma--a single-center experience.

AIMS: The aim of this study is to evaluate factors associated with the outcome after surgical resection and to compare the efficacy of surgery to transarterial chemoembolisation (TACE) in patients with advanced intrahepatic cholangiocarcinoma (IHC). MATERIALS AND METHODS: 273 patients with IHC treated in our department between 1997 and 2012 were included in our study. Patients were divided according to therapy into surgical (n = 130), TACE (n = 32), and systemic chemotherapy/best supportive care (n = 111) groups. Clinicopathological characteristics and survival were reviewed retrospectively. RESULTS: The 1-, 3-, and 5-year survival rates in patients after surgical resection were 60%, 40%, and 23%, respectively. Recurrence occurred in 63 percent of patients after R0 resection. Median time of recurrence-free survival was 14 months. Univariate analysis revealed nine significant risk factors for overall survival in the resection group: major surgery, extrahepatic resection, vascular and bile duct resection, lymph node invasion, poor tumour differentiation, positive surgical margin, multiple lesions, tumour diameter, and UICC-Stage. Multivariate analysis showed that lymph node metastasis (P < 0.001), poor tumour differentiation (P = 0.002), and positive resection margins (P = 0.001) were independent prognostic factors for survival. Median survival as well as overall survival rates of TACE patients were comparable to those of lymph node positive patients and patients with tumour positive surgical margins. CONCLUSIONS: R0 resection in patients with negative lymph node status remains the best chance for long-term survival in patients with IHC. There is no significant survival benefit of surgery in lymph node positive patients or patients with positive resection margin over TACE.

Melatonin induces transcriptional regulation of Bim by FoxO3a in HepG2 cells.

BACKGROUND: Melatonin induces apoptosis in many different cancer cell lines, including hepatocellular carcinoma cells. However, the responsible pathways have not been clearly elucidated. A member of the forkhead transcription factors' family, FoxO3a, has been implicated in the expression of the proapoptotic protein Bim (a Bcl-2-interacting mediator of cell death). In this study, we used human HepG2 liver cancer cells as an in vitro model to investigate whether melatonin treatment induces Bim through regulation by the transcription factor FoxO3a. METHODS: Cytotoxicity of melatonin was compared in HepG2 hepatoblastoma cells and primary human hepatocytes. Proapoptotic Bim expression was analysed by reverse transcriptase-polymerase chain reaction and western blot. Reporter gene assays and chromatin immunoprecipitation assays were performed to analyse whether FoxO3a transactivates the Bim promoter. Small interfering RNA (siRNA) was used to study the role of FoxO3a in Bim expression. Immunofluorescence was performed to analyse FoxO3a localisation in HepG2 cells. RESULTS: Melatonin treatment induces apoptosis in HepG2 cells, but not in primary human hepatocytes. The proapoptotic effect was mediated by increased expression of the BH3-only protein Bim. During melatonin treatment, we observed increased transcriptional activity of the forkhead-responsive element and could demonstrate that FoxO3a binds to a specific sequence within the Bim promoter. Furthermore, melatonin reduced phosphorylation of FoxO3a at Thr(32) and Ser(253), and induced its increased nuclear localisation. Moreover, silencing experiments with FoxO3a siRNA prevented Bim upregulation. CONCLUSION: This study shows that melatonin can induce apoptosis in HepG2 hepatocarcinoma cells through the upregulation of proapoptotic Bim mediated by nuclear translocation and activation of the transcription factor FoxO3a.

[Hilar cholangiocarcinoma: right versus left hepatectomy]. / Hiläres Cholangiokarzinom: rechts- versus linksseitige En-bloc-Resektion.

INTRODUCTION: Right-sided hepatectomy including segment 1 and right trisectionectomy are typical approaches to surgical treatment of hilar cholangiocarcinoma. In this study we have compared the oncological capacity of this approach to left-sided hepatectomy. PATIENTS AND PROCEDURES: In 223 patients referred to our institution 150 hepatic resections were performed: 14 hilar resections, 68 right and 68 left hepatectomies. RESULTS: Survival after curative (R0) and palliative surgery was significantly superior to that in patient with exploration or no surgery at all (p < 0.0001). 5- and 10-year survival after right versus left hepatectomy was 29 and 22 % versus 21 and 7 % (p = 0.204). If hospital mortality was eliminated, survival after right hepatectomy was marginally significantly superior to that after left-sided hepatectomy (p = 0.041). Hospital mortality was 13 % after right compared to 4 % after left hepatectomy (p = 0.069). The R situation was of prognostic importance following right and the N situation after left hepatectomy (p = 0.038 and 0.01, respectively). Vascular resection - in right-sided procedures performed as "hilar en bloc resection" - did not influence the outcome. CONCLUSIONS: Low perioperative mortality after left-sided resection and, obviously, inferior oncological radicality are features of left hepatectomy. These features do not detract from the importance of left hepatectomy which is an indispensable approach to surgically treated patients with hilar cholangiocarcinoma.

Localized modulation of rotating waves in Taylor-Couette flow.

We report the results of an experimental study on the multiplicity of states in Taylor-Couette flow as a result of axial localization of azimuthally rotating waves. Localized states have been found to appear hysteretically from time-dependent Taylor-Couette flow at Reynolds numbers significantly above the onset of wavy Taylor vortices. These localized states have the shape of a modulated rotating wave and differ significantly from global modulated wavy Taylor vortex states in their spatial characteristics. Axial localization of rotating waves is accompanied with a significant increase in size of the underlying pair of Taylor vortices. Our work reveals that localization provides a mechanism for the appearance of multiple time-dependent states in Taylor-Couette flow.

Ten years of simultaneous pancreas-kidney transplantation: a retrospective single-center analysis of prospectively obtained data.

INTRODUCTION: Simultaneous pancreas-kidney transplantation (SPK) is a standardized and life-saving procedure for a patient suffering from both insulin-dependent diabetes mellitus type 1 (IDDM 1) and end-stage diabetic nephropathy. To expand the donor pool and to determine the influence of the preprocurement pancreas suitability scoring system (P-PASS) on pancreas graft survival we retrospectively analyzed our data on SPK. PATIENTS AND METHODS: From 1999 to 2010 we performed 55 SPKs, using systemic-enteric drainage as surgical approach. The immunosuppressive therapy was induced with basiliximab; maintenance therapy was based on tacrolimus, mycophenolate mofetil, and steroids. Data were prospectively obtained, analyzed, and correlated to the P-PASS. RESULTS: The overall 10-year patient survival rate was 78% with a 10-year pancreas survival rate of 53%. Three patients needed retransplantation of SPK and 6 patients needed singular pancreas retransplantation. Seventeen patients showed acute rejection episodes and 14 patients suffered from cytomegalovirus (CMV) infections. We compared 43 patients receiving organs from an "ideal" donor (P-PASS <17) with 12 patients receiving grafts from "marginal" donors (P-PASS ≥17). Neither P-PASS nor donor age demonstrated significant influence on pancreas graft survival. However, the body mass index (BMI) of the donor showed a negative tendency (P = .059). CONCLUSION: The P-PASS showed no significant prediction of pancreas graft survival. In view of our data, expansion of the German donor pool is possible. A multicenter study of SPK using "marginal" pancreas grafts is mandatory to define a realistic "cut-off" value for P-PASS.

Liver transplantation for hepatocellular carcinoma--is there a risk of recurrence caused by intraoperative blood salvage autotransfusion?

BACKGROUND/AIMS: The use of intraoperative blood salvage autotransfusion (IBSA) during surgical approaches may contribute to tumour cell dissemination. Therefore, IBSA should be avoided in cases of malignancy. However, the risks of IBSA might be acceptable in liver transplantation (LT) for selected small hepatocellular carcinoma (HCC). METHODS: In total, 136 recipients of LT with histologically proven HCC in the explanted liver were included in this analysis. With regard to tumour recurrence, 40 patients receiving IBSA despite HCC (IBSA group) were compared to 96 patients without IBSA (non-IBSA group). RESULTS: Milan criteria as assessed in the explanted liver were fulfilled in 24 of 40 IBSA patients and 58 of 96 non-IBSA patients (p = 0.85). Five of 40 patients in the IBSA group and 18 of 96 patients in the non-IBSA group experienced tumour recurrence (p = 0.29). In spite the theoretical risk of tumour cell dissemination, the recurrence rate was not increased in the IBSA group. CONCLUSION: Our results indicate that IBSA does not modify the risk of HCC recurrence. Therefore, in highly selected HCC patients undergoing LT, the use of IBSA appears to be justified.

Implantation of the liver during reperfusion of the heart in combined heart-liver transplantation: own experience and review of the literature.

BACKGROUND: There are only a few reports about combined heart-liver transplantations. The surgical techniques differ widely, ranging from sequential implantation of the organs to simultaneous transplantations. We report our experience with simultaneous, combined heart-liver transplantations without using a veno-venous bypass demonstrating that this is a feasible surgical technique. METHODS: Since 2005, we performed 4 combined heart-liver transplantations by implanting the liver during the reperfusion period of the newly implanted heart. We retrospectively reviewed patient clinical data and outcomes. RESULTS: The mean operative time was 534 ± 247 minutes and the ischemia times for heart and liver were 190 ± 72 minutes (cold ischemia time for the heart), 98 ± 96 minutes (warm ischemia time for the heart), 349 ± 101 minutes (cold ischemia time for the liver), and 36.25 ± 3.5 minutes (warm ischemia time for the liver). Three patients were discharged from the hospital after an uneventful clinical course. One patient died due to multi-organ failure during the intensive care unit stay on the 23rd postoperative day. CONCLUSION: We suggest that combined, simultaneous heart-liver transplantation without veno-venous bypass is a feasible surgical technique.

Laparoscopic incisional hernia repair after solid-organ transplantation.

BACKGROUND: Incisional hernias are a frequent problem after liver transplantation. Mesh repair techniques including laparoscopic repair have been employed in order to address this problem. We have introduced intraperitoneal onlay mesh repair (IPOM) in 2008 because of advantages that had been reported in the literature. To perform a structured comparison of methods and outcomes, we compared patients who have been treated with IPOM and those who have been treated conventionally. METHODS: We included 29 consecutive patients (15 IPOM, 14 conventional hernia repair [CHR] who have been analyzed and have been examined clinically and sonographically during their follow-up. RESULTS: Recurrence rate was 6% (IPOM) and 50% (CHR), complication rate was 33% (IPOM) and 21% (CHR), mean hospital stay was 7.2 (IPOM) and 9.7 (CHR) days. None of the 29 patients had an impaired wound healing or infectious complications. Of the 29 patients, 10 received sirolimus for immunosuppression, which was switched preoperatively to a calcineurin inhibitor. CONCLUSION: IPOM results in a shorter hospital stay. The complication rate with IPOM was higher compared with CHR, recurrence rate was considerably lower. The role of perioperative sirolimus switch needs to be interpreted with caution, but should be further investigated because of potential advantages with respect to fewer wound healing complications.

Acute renal failure and liver dysfunction after subcutaneous injection of 3-sn-phosphatidylcholine (Lipostabil®)-case report.

INTRODUCTION: Drug-induced tubulointerstitial nephritis and acute tubular necrosis are common, and are often caused by drugs especially antibiotics or non-steroidal anti-inflammatory drugs. Drug-induced liver dysfunction and renal failure after subcutaneous injection of phosphatidylcholine was not reported so far. 3-sn-Phosphatidylcholine has been described as a cell lysis reaction-inducing drug. Its in vitro data indicated a relevant toxicity potential. In particular human cell types such as fibroblast-like preadipocytes, vascular and skeletal muscle cells, or renal epithelial cells react more sensitive than other human cell types. CASE REPORT: We present a 28-year-old woman who received 3.5 g (70 mL) of 3-sn-phosphatidylcholine (Lipostabil®) at once subcutaneously (s. c.) in both gluteal regions. The drug was originally introduced to prevent fat embolism. Nevertheless, its off-label use in aesthetic therapy for treatment of localized fat deposits through subcutaneous administration is becoming increasingly common. Three hours after injection the patient suffered from severe nausea and emesis. Within 24 hours a dramatic increase of liver enzymes and a beginning liver dysfunction were observed. Subsequently, renal function deteriorated two days later making a temporary haemodialysis necessary. Hepatic improvement was observed after three days of treatment. Renal function was fully recovered after two weeks. CONCLUSION: To the best of our knowledge, this is the first reported patient presenting with acute liver dysfunction and renal failure after subcutaneous injection of 3-sn-phosphatidyl-choline (Lipostabil®) indicating the risk of an off-label use of this drug.

Further evidence for the efficacy of a metacognitive group training in schizophrenia.

Metacognitive training (MCT) for patients with schizophrenia is a novel psychological group treatment targeting cognitive biases putatively involved in the pathogenesis of schizophrenia (e.g. jumping to conclusions, overconfidence in errors). Its eight modules are available cost-free online in many languages. In the present study, 36 subacute or remitted patients were randomly allocated to either the MCT or a wait-list group who received treatment-as-usual (TAU). Baseline and post assessments were 8 weeks apart and were performed blind to group status. MCT showed significantly greater improvement on the following parameters relative to the TAU group: delusion distress (PSYRATS), memory and social quality of life. In the MCT group, the rate of jumping to conclusions bias was reduced after training. No differences occurred on the PANSS. The present study confirms prior reports that MCT exerts beneficial effects on some cognitive and symptomatic parameters.

[Hepatocellular carcinoma and cholangiocarcinoma]. / Hepatozelluläres Karzinom und Cholangiokarzinom.

Hepatocellular carcinoma and cholangiocarcinoma are relatively rare tumors of the gastrointestinal tract in western Europe but their incidence has been increased in recent years. Newly diagnosed intrahepatic lesions or intrahepatic cholestasis require extensive laboratory tests and imaging studies in order to confirm the diagnosis of hepatocellular carcinoma, intrahepatic or extrahepatic cholangiocarcinoma. The treatment options range from liver resection or liver transplantation to conservative measures (in cases of non-resectable lesions). This review article aims to provide an overview on the diagnostic options and the subsequent treatment.