[Expert recommendations: Hepatitis C and transplantation]. / Empfehlungen zur antiviralen Therapie der chronischen Hepatitis C bei Patienten auf der Warteliste und nach Transplantation.

With the approval of new direct acting antiviral agents (DAA), therapeutic options for patients with chronic hepatitis C virus (HCV) infection are now generally available before and after liver transplantation (LT). Interferon-free DAA regimens are highly effective therapies and provide a good safety profile. However, the body of clinical evidence in this patient population is limited and the best treatment strategies for patients on the waiting list with (de)compensated cirrhosis and after LT are not well defined. The following recommendations for antiviral therapy in the context of LT are based on the currently available literature and clinical experience of experts in the field, and have been discussed in an expert meeting. The aim of this article is to guide clinicians in the decision making when treating patients before and after LT with DAAs.

Activation of natural killer cells by hepatitis C virus particles in vitro.

Little is known about the ability of hepatitis C virus (HCV) to alter early innate immune responses in infected patients. Previous studies have shown that natural killer (NK) cells are functionally impaired after interaction of recombinant HCV glycoprotein E2 with the co-stimulatory CD81 molecule in vitro; however, the functional consequences of a prolonged contact of NK cells with HCV particles have remained unclear. We have examined the phenotypes of purified, interleukin-2-activated NK cells from healthy donors and HCV genotype 1b patients after culture for 5 days with HCV pseudoparticles (HCVpp) and serum samples containing HCV genotype 1b. NK cells from healthy donors and chronic HCV patients were found to up-regulate receptors associated with activation (NKp46, NKp44, NKp30, NKG2D), while NK receptors from the killer cell immunoglobulin-like receptor family (KIR/CD158), predominantly having an inhibitory function, were significantly down-modulated after culture in the presence of HCV particles compared with control cultures of NK cells. HCV-infected sera and HCVpp elicited significantly higher secretion of the NK effector lymphokines interferon-γ and tumour necrosis factor-α. Furthermore, HCV stimulated the cytotoxic potential of NK cells from normal donors and patients. The enhanced activation of NK cells after prolonged culture with HCVpp or HCV-containing sera for 5 days suggests that these innate effector cells may play an important role in viral control during early phases of HCV infection.

[Right-sided or left-sided donor nephrectomy-is this really relevant?] / Rechts- oder linksseitige Donornephrektomie ­ ist das wirklich relevant?

BACKGROUND: In the context of living donation, the protection of the donor and the outcome are very important aspects. However, the side selection of the donor nephrectomy is also decisive. In this work, the basics of side selection and the question of whether there are differences regarding the left-sided or right-sided donor nephrectomy are considered. MATERIALS AND METHODS: Living kidney donation data of our center between December 2004 and July 2019 were evaluated in terms of withdrawal side, complications and outcome, as well as the current literature in PubMed. Finally, the results from our center are compared with the current literature. RESULTS: During the investigation period, 152 live donations were carried out in our center. In these cases 66 patients had a left-sided and in 86 cases a right-sided donor nephrectomy. One transplant vein thrombosis occurred in each group. Complications and outcome were similar for the recipient in both groups. It was noticed in the current literature that generally more left-sided donor nephrectomies are performed, most likely due to the preference of the surgeon. Although a low significantly increased risk of transplant vein thrombosis after right-sided donor nephrectomy is described, all authors agree that right-sided donor nephrectomy is a safe procedure with good outcome. CONCLUSIONS: Our own results and the current literature show that the right-sided donor nephrectomy is a safe procedure with only a slightly increased risk of complications compared to the left side and therefore can be recommended. It is clearly safe for the donor and organ, with an equivalent outcome for the recipient. The results are also dependent on the experience of the surgeon.

Transperitoneal, hand-assisted laparoscopic donor nephrectomy: surveillance of renal function by immune monitoring.

UNLABELLED: The history of living donor nephrectomy has undergone several development phases with respect to medical, immunologic, and operative aspects. Due to the shortage of postmortem organ donations and the rising number of patients with terminal renal insufficiency who are awaiting kidney transplantation, living kidney donation has become increasingly important during recent years. METHODS: From December 2004 to May 2005, we performed hand-assisted laparoscopic donor nephrectomies on 15 female and 9 male patients of median age 37 years. Our immunosuppressive regimen included tacrolimus, mycophenolate mofetil, methylprednisolone, and a monoclonal antibody. RESULTS: The median operative time was 138 minutes (113-180 minutes), and the median warm ischemia time was 87 seconds (63-150 seconds); results comparable to those of open donor nephrectomy. The hospitalization periods of the donors were between 5 and 7 days. The renal function and acute-phase parameters showed a transient increase during and after the operation. Most of the patients reached baseline levels by postoperative day 3 or 4. CONCLUSION: Together with the clinical data, these findings confirmed the efficacy and minimal invasiveness of laparoscopic donor nephrectomy. It is thus possible that in the future this operative method will become the procedure of choice.

[Organ donation in Germany: Don't we want to? Can't we? Or are we not allowed?] / Organspende in Deutschland: Wollen wir nicht? Können wir nicht? Oder dürfen wir nicht?

Organ donation has reached a new low in Germany. The number of organ donations dropped from 1296 in 2010 to just 797 organ donations in 2017. This represents a decrease of 916 kidney transplants in the last six years. Thus, Germany occupies the penultimate position in the Eurotransplant association with the number of organ donors per million inhabitants. Only Luxembourg has fewer because of foreigners proportion of 47.5% and many of them lives in the neighboring european countries. However, Germany is not only far behind in the Eurotransplant association with the number of organ donors, but Germany is also at the bottom in comparison with other European countries with comparable political, ethical, religious and social structures-are we so different from our European neighbors? Germany is a country with one of the best health care systems in the world, but not in the field of organ donation. In an international comparison of organ donation, even emerging economies are in a far better position than Germany. Thus, we should ask ourselves if a flaw in the system is leading to this organ donor shortage. But what is the cause and how can we change it? There is no single and general solution to this problem. There are many different points to consider and tackle. These include educating the population, indicating of the will to donate organs or its rejection, training physicians to recognize potential organ donors, support for transplant officers, and much more. In particular, however, thought should be given to an opt-out (presumed consent) solution. It is time to question the system of organ donation in Germany and to discuss it objectively.

Safety of Direct-Acting Antiviral Therapy Regarding Renal Function in Post-Liver Transplant Patients Infected with Hepatitis C Virus and a 100% 12-Week Sustained Virologic Response-A Single-Center Study.

BACKGROUND: Patients after liver transplantation (LT) with hepatitis C virus (HCV) infection often suffer from renal or hepatic impairment. Treating patients after LT with direct-acting antivirals (DAA) might result in decreasing renal function due to interaction of DAA and immunosuppressive therapy. In this single-center study we analyzed clinical parameters of 18 HCV-infected patients treated with DAA therapy after LT. METHODS: The primary end points were change of renal function (glomerular filtration rate) and sustained virologic response 12 weeks after therapy (SVR12). For secondary end points, we investigated the influence of DAA therapy on transaminases, bilirubin, international normalized ratio, noninvasive fibrosis measurement, and Model for End-Stage Liver Disease (MELD) score. RESULTS: Five out of 18 patients treated with DAA suffered from renal impairment stage 2, and 7 patients of renal impairment stage 3. Renal function at SVR12 was not influenced by preexisting renal impairment (P > .5), type of immunosuppressant (P > .5), or type of DAA regimen (P > .5). All patients reached SVR12. The levels of transaminases and bilirubin declined rapidly, as expected. Ten out of 18 patients already suffered from cirrhosis or liver fibrosis >F3 according to noninvasive measurement before initiation of treatment. Single-point acoustic radiation force impulse imaging improved in 9 patients (P = .012). In 7 patients, MELD score improved owing to the decrease of bilirubin levels. In 6 patients it worsened. CONCLUSIONS: DAA therapy in LT patients was effective and safe in this single-center real-life cohort. Renal function was not influenced by the administered drug combinations, even in patients with preexisting renal impairment.

[Radiation cystitis : Pathophysiology and treatment]. / Radiogen bedingte Zystitis : Pathophysiologie und Therapie.

Radiation cystitis (RC) is a common side-effect of radiation to the pelvis. Their clinical appearance as well as their degree of expression is manifold, as are the therapeutic options. However, in the absence of randomized examinations, recommendations are difficult. We differentiate between oral, systemic therapies, intravesical instillations and interventions as well as interventional, radiological and, as an ultima ratio, surgical treatments. This article provides an overview of the different treatment options with particular emphasis on the conservative-interventional therapy options.

The hexa- and pentapeptide extension of proalbumin. II. Processing of specific antibodies against the synthetic hexapeptide.

The chemically synthesized proalbumin hexapeptide was coupled to rabbit albumin with carbodiimide. Subsequently rabbits were immunized by subcutaneous injection of the conjugate. After 5 weeks the rabbits had developed antibodies against the hexapeptide, which could be detected by immunodiffusion. A sensitive enzyme-linked immunosorbent assay was developed. Using the hexapeptide and other very similar peptides as antigens, a high specificity of the antibodies against the proalbumin hexapeptide was found.

The hexa- and pentapeptide extension of proalbumin. I. Chemical synthesis of serum albumin propeptides.

The proalbumin hexapeptide extension was synthesized beginning from the C-terminal end by stepwise N-terminal peptide chain elongation starting from N-tert-butyloxycarbonyl-(Ng-nitro)arginyl-(Ng-nitro)arginine 4-nitrobenzyl ester; [alpha](20)365-12 degrees C (c = 1; dimethylformamide). The other amino acids were incorporated by excess mixed anhydrides of Ddz-amino acids (Ddz; 3,5-dimethoxyphenylisopropyloxycarbonyl) yielding the fully protected hexapeptide in crystalline quality. After removal of the protective groups by acid treatment and hydrogenation the peptide was purified by Dowex ion-exchange and Sephadex chromatography. The purity was confirmed by thin-layer chromatography and amino acid analysis.

[Living kidney donation - an overview]. / Lebendnierenspende - ein aktueller Überblick.

BACKGROUND: The living kidney donation has become increasingly important in recent years. Because of the decreasing number of postmortem donors, there has been a dramatic increase in morbidity and mortality due to the long waiting times for patients on dialysis. By timely living donation after dialysis entry or even preemptively, this can be avoided. AIM: In addition, the living donor has better graft function and better graft survival which is due to the predictability of the donation, the optimal conditioning of donor and recipient, and the short ischemia time. To protect the donor, to provide legal protection, and to avoid abuse, the German legislature reacted with the Transplantation Act and its amendment. The recent recommendations for donor evaluation from the Amsterdam Forum have been used by the Federal Medical Council to revise current guidelines and guidelines for living donation will be drawn up. CONCLUSION: The focus of these efforts is standardization of the procedure and protection of the kidney donor. This is also reflected in the recommendations for organ removal technique and the selection of the organ to be used for kidney donation.

The hexa- and pentapeptide extension of proalbumin: lack of peptide-induced histamine-releasing activity by this hexapeptide in rat mast cells and human leucocytes.

It is well documented that small basic peptides with lipophilic counterparts induce non-cytolytic histamine release particularly from rat peritoneal mast cells, and to a lesser extent from human leukocytes. Since pro-albumin hexapeptide with its lipophilic core also exhibits a high percentage of basic amino acid residues, it was thought valid to investigate its potential histamine releasing activity using the above-mentioned cell systems. Results show that the peptide failed in both cell types to induce histamine release, or to inhibit IgE mediated or anaphylatoxin induced histamine release up to concentrations of 10(-4) M.

Aldehyde oxidizing capacity of erythrocytes in normal and alcoholic individuals.

The acetaldehyde metabolizing capacity in blood of alcoholics and nonalcoholics was investigated by an improved head-space gas chromatographic method. Great individual and interindividual variability was observed. The mean acetaldehyde oxidizing capacity of 3.51 nmoles/min/ml erythrocyte suspension in alcoholics was significantly lower than the mean of 5.20 nmoles/min/ml in nonalcoholics. Furthermore, treatment of alcoholics with aldehyde dehydrogenase inhibitors reduced the acetaldehyde oxidizing capacity significantly (mean of 1.67 nmoles/min/ml). No acetaldehyde could be detected in blood of nonalcoholics who ingested 0.25 g ethanol/kg body weight whereas levels of 2-14 microM were detected in blood of alcoholics. After disulfiram, an elevation to 7-103 microM in blood of alcoholics was observed.

A cart cage for transferring macaques, capuchins, and small dogs.

A novel mobile monkey transport cart cage allows ease of handling, safety, secure holding, good visual access to the monkeys, room for large macaques, and ease of assembly, all at a modest cost.

Cytomegalovirus infection after liver transplantation incidence, risks, and benefits of prophylaxis.

BACKGROUND: Cytomegalovirus (CMV) infection and related disease is a feared complication after liver transplantation. Antiviral prophylaxis is recommended in clinical practice guidelines depending on the CMV status of both donor and recipient as well as the individual risk profile. METHODS: We retrospectively analyzed 211 liver transplant recipients with respect to the incidence of CMV infection after transplantation, the influence of donor and recipient CMV status, and the effect of antiviral prophylaxis. In addition, the underlying liver disease and immunosuppressive regimen were compared with the incidence of CMV infection. Patients were divided into 4 groups according to CMV donor/recipient (D/R) profile: group A (D-/R-) 28 patients (13.3%), group B (D-/R+) 64 patients (30.3%), group C (D+/R+) 79 patients (37.4%), and group D (D+/R-) 40 patients (19.0%). RESULTS: CMV infection was observed in 17.9%, 29.7%, 24.1%, and 22.5% of the patients, respectively, with no significant difference in infection rates between the groups. CMV infection occurred in 5 patients (17.9%) in the presumed low-risk profile (group A), despite an antiviral prophylaxis in 4 out of these 5 patients. In contrast, CMV infection occurred in only 9/40 patients (22.5%) in the presumed high-risk profile (group D). The most frequent infection rates were found in groups B and C (R+ groups). After successful treatment of CMV infection, no recurrence was detected. Underlying liver disease or immunosuppressive protocol had no influence on CMV infection. CONCLUSION: Approximately one fourth of patients will acquire CMV infection after liver transplantation independent of donor/recipient status. Surprisingly, antiviral prophylaxis does not seem to be sufficient to reduce this proportion of patients, either in presumed high-risk or in presumed low-risk situations.