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Purpose: Ischemia reperfusion injury represents a significant yet difficult to assess risk factor for short- and long-term graft impairment in human liver transplantation (LT). As a non-invasive, non-ionizing tool, hyperspectral imaging (HSI) is capable of correlating optical properties with organ microperfusion. Hence, we here performed a study of human liver allografts assessed by HSI for microperfusion and prediction of initial graft function., Methods: Images of liver parenchyma of 37 human liver allografts were acquired at bench preparation, during normothermic machine perfusion (NMP), if applicable, and after reperfusion in the recipient. A specialized HSI acquisition software computed oxygen saturation (StO2), tissue hemoglobin indices (THI), near infrared perfusion indices (NIR), and tissue water indices (TWI). HSI parameters were analyzed for differences with regard to preservation technique, reperfusion sequence and presence of early allograft dysfunction (EAD)., Results: Organ preservation was performed by means of NMP (n = 31) or static cold storage (SCS; n = 6). Patients' demographics, donor characteristics, presence of EAD (NMP 36.7% vs. SCS 50%, p = 0.6582), and HSI parameters were comparable between both groups of preservation method. In organs developing EAD, NIR at 1, 2, and 4 h NMP and after reperfusion in the recipient was significantly lower (1 h NMP: 18.6 [8.6-27.6] vs. 28.3 [22.5-39.4], p = 0.0468; 2 h NMP: 19.4 [8.7-30.4] vs. 37.1 [27.5-44.6], p = 0.0011; 4 h NMP: 26.0 [6.8-37.1] vs. 40.3 [32.3-49.9], p = 0.0080; reperfusion: 13.0 [11.5-34.3] vs. 30.6 [19.3-44.0], p = 0.0212)., Conclusion: HSI assessment of human liver allografts is feasible during organ preservation and in the recipient. NIR during NMP and after reperfusion might predict the onset of EAD. Larger trials are warranted for assessment of this novel technique in human LT., (© 2024. The Author(s).)

Background: The scarcity of available liver grafts necessitates the use of organs from extended criteria donors, a practice associated with an increased risk of graft failure. A notable percentage of deceased donor liver allografts are rejected due to subjective criteria. Normothermic machine perfusion holds promise for introducing objective parameters into this decision-making process. The aim of this study was to compare the outcomes of standard criteria and extended criteria donor allografts after liver transplantation, following viability assessment, using normothermic machine perfusion., Methods: Liver allografts preserved by normothermic machine perfusion before liver transplantation at the University Hospital of Münster were retrospectively analyzed. Organs were stratified according to the Eurotransplant Donor Risk Index. In total, 101 liver grafts were included in this study and divided into 2 groups: (1) standard criteria donors with a Donor Risk Index <1.8 (DRI-low) and (2) extended criteria donors with a Donor Risk Index ≥1.8 (DRI-high)., Results: An increased risk profile of donor livers, as assessed by the Eurotransplant Donor Risk Index, did not correlate with patient or graft survival. High-risk liver grafts were effectively transplanted into recipients with different risk levels after viability assessment by normothermic machine perfusion. However, the recipients' model for end-stage liver disease scores showed a significant association with both overall patient and graft survival., Conclusion: The use of normothermic machine perfusion for viability assessment allows safe transplantation of high-risk donor livers and effectively addresses the disparity between donor liver availability and transplantation demand., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: In recent years, several international studies have been published, that describe a relationship between country of origin and the occurrence of work-related injury. Since we regularly treat migrant workers in our hospital after work-related injury, we wanted to gain more insight into the characteristics of this group., Design: Descriptive retrospective cohort study., Method: Patients were identified from the Dutch Nationwide Trauma Registration (LTR). Patients that were included in the study were admitted and treated in our hospital after a work-related injury from 2017 to 2021. Additional information regarding patient characteristics and outcomes were retrieved from our electronic hospital information system., Results: 14,9% of the 397 patients were found to have an injury with an Injury Severity Score (ISS) of 16 or higher. The most common mechanism of injury was a fall from height (ISS≤15: 26.0%, ISS≥16: 57.6%). In the study population, 15,4% had a non-Dutch origin. The majority consisted of employees with an Eastern European nationality (70,5%), mainly from Poland. Within this group relatively more often patients were encountered that had no valid insurance (14% of patients with an Eastern European origin) or were intoxicated (19% of patients with Eastern European origin)., Conclusion: A relatively large part of our patient population consisted of migrant workers. We did not observe large differences in mechanism of injury, severity of injury and outcome between native patients and migrant workers. We did observe a relatively high frequency of insurance problems and intoxications among migrant workers.

Cigarette smoking is a common risk factor associated with negative long-term outcomes in kidney transplant recipients. However, whether donor smoking decreases graft longevity or negatively impacts recipient survival after kidney transplantation remains unknown. Therefore, this study aims to investigate the long-term outcome in patients who received a kidney graft from a deceased smoking or non-smoking donor. A total of 580 patients were divided into two groups: patients who received a graft from a smoking donor ( n = 276) and those who received a graft from a non-smoking donor ( n = 304). Analysis of demographic factors showed that the non-smoking cohort was older, had more extended criteria donors and longer warm ischemia times. The primary composite endpoint of patient and graft survival was better in the smoking donor cohort when analyzed using Kaplan-Meier method but not when controlled for covariates in multivariate analyses. These findings do not support a previously reported negative impact of deceased donor smoking on kidney transplant recipients. Thus, the underlying results should not be interpreted in favor of a positive donor smoking history, but rather remind the transplant community that donor smoking should not be considered as a deciding factor in refusing an otherwise acceptable kidney graft., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Becker, Pollmann, Funke-Kaiser, Görlich, Katou, Morgül, Kneifel, Reuter, Pascher and Houben.)

Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor and a leading cause of cancer-related deaths worldwide. However, current diagnostic tools are often invasive and technically limited. In the last decade, non-invasive liquid biopsies have transformed the field of clinical oncology, showcasing the potential of various liquid-biopsy derived analytes, including extracellular vesicles (EVs), to diagnose and monitor HCC progression and metastatic spreading, serving as promising novel biomarkers. A prospective single-center cohort study including 37 HCC patients and 20 patients with non-malignant liver disease (NMLD), as a control group, was conducted. Serum EVs of both groups were analyzed before and after liver surgery. The study utilized microbead-based magnetic particle sorting and flow cytometry to detect 37 characteristic surface proteins of EVs. Furthermore, HCC patients who experienced tumor recurrence (R-HCC) within 12 months after surgery were compared to HCC patients without recurrence (NR-HCC). EVs of R-HCC patients (n = 12/20) showed significantly lower levels of CD31 compared to EVs of NR-HCC patients (p = 0.0033). EVs of NMLD-group showed significantly higher expressions of CD41b than EVs of HCC group (p = 0.0286). The study determined significant short-term changes in CD19 dynamics in EVs of the NMLD-group, with preoperative values being significantly higher than postoperative values (p = 0.0065). This finding of our pilot study suggests EVs could play a role as potential targets for the development of diagnostic and therapeutic approaches for the early and non-invasive detection of HCC recurrence. Further, more in-depth analysis of the specific EV markers are needed to corroborate their potential role as diagnostic and therapeutic targets for HCC., (© 2024. The Author(s).)

A review and discussion of the current literature on liver transplantation for acute-on-chronic liver failure (ACLF) was performed. The ACLF represents an acute deterioration of liver function with pre-existing liver disease and is associated with increasing multiorgan failure, depending on the stage. The 28-day mortality ranges to well over 70% in stage 3 and requires rapid intensive medical treatment involving an interdisciplinary team experienced in transplantation medicine. Under optimized conditions, liver transplantation provides long-term survival rates comparable to other indications. Achieving this requires a differentiated donor selection, choosing the appropriate time for transplantation in the context of a dynamic disease course and the use of appropriate surgical techniques., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Donor proteinuria (DP) is a common but rarely evaluated aspect of today's kidney transplant allocation process. While proteinuria after kidney transplantation is a risk factor for impaired graft function and survival, the long-term effects of DP in kidney transplantation have not yet been evaluated. Therefore, this study aims to investigate the impact of DP on the long-term outcome after kidney transplantation. A total of 587 patients were found to be eligible and were stratified into two groups: (1) those receiving a graft from a donor without proteinuria (DP-) and (2) those receiving a graft from a donor with proteinuria (DP+). At 36 months, there was no difference in the primary composite endpoint including graft loss and patient survival (log-rank test, p = 0.377). However, the analysis of DP+ subgroups showed a significant decrease in overall patient survival in the group with high DP ( p = 0.017). DP did not adversely affect patient or graft survival over 36 months. Nevertheless, this work revealed a trend towards decreased overall survival of patients with severe proteinuria in the subgroup analysis. Therefore, the underlying results suggest caution in allocating kidneys from donors with high levels of proteinuria., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pollmann, Vogel, Pongs, Katou, Morgül, Houben, Görlich, Kneifel, Reuter, Pollmann, Pascher and Becker.)

Background: Graft-versus-host disease following liver transplantation is a serious and usually fatal complication. Data identifying the risk factors and specifying the diagnosis and treatment options of the disease are scarce and contentious. Moreover, recommendations for therapeutic approaches are similarly sparse., Methods: A systematic review of the literature from 1988 to 2020 on graft-versus-host disease following liver transplantation was performed using the PubMed and MEDLINE databases. Medical subject headings, such as graft-versus-host disease and GvHD were used in combination with solid organ transplant, transplantation, or liver transplant. Following duplicate removal, 9298 articles were screened for suitability. A total of 238 full-text articles were analyzed for eligibility, resulting in 130 eligible articles for meta-analysis. Two hundred twenty-five patients developing graft-versus-host disease following liver transplantation reported herein were mainly published in case reports and case series., Results: Graft-versus-host disease occurred with an incidence of 1.2%. 85% developed following deceased donor liver transplant and 15% following living-related donor liver transplantation. The median follow-up period following liver transplantation was 84 days (interquartile range, 45-180). The median time from liver transplantation to graft-versus-host disease onset was 30 days (interquartile range, 21-42). The main clinical features included skin rash (59%), fever (43%), diarrhea (36%), and pancytopenia (30%). The overall mortality rate was 71%. Neither univariate (HR = 0.999; 95% CI, 0.493-2.023; p = 1.0) nor multivariate Cox regression analysis revealed a significant correlation between adaptation of immunosuppression and survival probability (HR = 1.475; 95% CI, 0.659-3.303; p = 0.3)., Conclusions: This systematic review suggests that an increase in immunosuppressive regimen does not yield any survival benefit in patients suffering from graft-versus-host disease following liver transplantation., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Purpose: Atypical variants of the hepatic artery are common and pose a technical challenge for normothermic machine perfusion (NMP). The transplant surgeon has three options when confronted with hepatic arterial variation in a liver graft to be subjected to NMP: to perform arterial reconstruction (i) prior, (ii) during, or (iii) following NMP., Methods: Herein, we report our experience and technical considerations with pre-NMP reconstruction. Out of 52 livers, 9 had an atypical hepatic artery (HA): 3 replaced right HA, 3 replaced left HA, 1 accessory left HA, 1 accessory left and right HA, and 1 replaced left and right HA., Results: Reconstruction was conducted during back-table preparation. A single vascular conduit was created in all grafts to allow single arterial cannulation for NMP, necessitating only one arterial anastomosis within the recipient. All grafts were subjected to NMP and subsequently successfully transplanted., Conclusion: Our approach is being advocated for as it preserves the ability to alter the reconstruction in case of problems resulting from the reconstruction itself, thereby allowing functional evaluation of the reconstruction prior transplantation, permitting simultaneous reperfusion in the recipient, and providing the shortest possible duration for vascular reconstruction once the graft is rewarming non-perfused within the recipient. In addition, in light of the frequency of technically demanding reconstructions with very small vessels, we consider our technique beneficial as the procedure can be performed under ideal conditions at the back-table., (© 2022. The Author(s).)

Normothermic machine perfusion (NMP) is nowadays frequently utilized in liver transplantation. Despite commonly accepted viability assessment criteria, such as perfusate lactate and perfusate pH, there is a lack of predictive organ evaluation strategies to ensure graft viability. Hyperspectral imaging (HSI)-as an optical imaging modality increasingly applied in the biomedical field-might provide additional useful data regarding allograft viability and performance of liver grafts during NMP., Methods: Twenty-five deceased donor liver allografts were included in the study. During NMP, graft viability was assessed conventionally and by means of HSI. Images of liver parenchyma were acquired at 1, 2, and 4 h of NMP, and subsequently analyzed using a specialized HSI acquisition software to compute oxygen saturation, tissue hemoglobin index, near-infrared perfusion index, and tissue water index. To analyze the association between HSI parameters and perfusate lactate as well as perfusate pH, we performed simple linear regression analysis., Results: Perfusate lactate at 1, 2, and 4 h NMP was 1.5 [0.3-8.1], 0.9 [0.3-2.8], and 0.9 [0.1-2.2] mmol/L. Perfusate pH at 1, 2, and 4 h NMP was 7.329 [7.013-7.510], 7.318 [7.081-7.472], and 7.265 [6.967-7.462], respectively. Oxygen saturation predicted perfusate lactate at 1 and 2 h NMP (R 2 = 0.1577, P = 0.0493; R 2 = 0.1831, P = 0.0329; respectively). Tissue hemoglobin index predicted perfusate lactate at 1, 2, and 4 h NMP (R 2 = 0.1916, P = 0.0286; R 2 = 0.2900, P = 0.0055; R 2 = 0.2453, P = 0.0139; respectively)., Conclusions: HSI may serve as a noninvasive tool for viability assessment during NMP. Further evaluation and validation of HSI parameters are warranted in larger sample sizes., (Copyright © 2022 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

Kidney allografts are subjected to ischemia reperfusion injury during the process of transplantation. Hypothermic machine perfusion (HMP) of deceased donor kidneys from organ procurement until transplantation is associated with a superior outcome when compared to static cold storage (SCS). Nevertheless, cold ischemia time (CIT) remains an independent risk factor for delayed graft function (DGF) in HMP-preserved kidney allografts as well. We performed a retrospective single-center study including all adult recipients who underwent deceased donor kidney-only transplantation at our center between January 2019 and December 2020. Beside the clinicopathological donor and recipient data, flow and resistance data during HMP were assessed. Short- and long-term kidney allograft outcome after end-ischemic HMP and SCS were analyzed and compared. Organ preservation consisted of either SCS (n = 88) or HMP (n = 45). There were no differences in recipient demographics and donor details between groups. CIT was significantly longer in the HMP group (16.5 [8.5−28.5] vs. 11.3 [5.4−24.1], p < 0.0001). The incidence of DGF as well as serum creatinine at discharge and at 1 year post transplant were comparable between groups. Duration of SCS prior to HMP was comparable among grafts with and without DGF. Flow rate and organ resistance at the start of HMP were significantly worse in DGF-kidney grafts (arterial flow 22.50 [18.00−48.00] vs. 51.83 [25.50−92.67] ml/min, p = 0.0256; organ resistance 123.33 [57.67−165.50] vs. 51.33 [28.17−111.50] mmHg/mL/min, p = 0.0050). Recipients with DGF had significantly worse creatinine levels at discharge (2.54 [1.08−7.64] vs. 1.67 [0.90−6.56], p < 0.0001) and at 1 year post transplant (1.80 [1.09−7.95] vs. 1.59 [0.87−7.40], p = 0.0105). In conclusion, baseline HMP parameters could be applied as a predictive tool for initial graft function, which in turn determines long-term outcome.

Introduction: In liver transplantation (LT), steatosis is commonly judged to be a risk factor for graft dysfunction, and quantitative assessment of hepatic steatosis remains crucial. Liver biopsy as the gold standard for evaluation of hepatic steatosis has certain drawbacks, that is, invasiveness, and intra- and inter-observer variability. A non-invasive, quantitative modality could replace liver biopsy and eliminate these disadvantages, but has not yet been evaluated in human LT., Methods: We performed a pilot study to evaluate the feasibility and accuracy of hyperspectral imaging (HSI) in the assessment of hepatic steatosis of human liver allografts for transplantation. Thirteen deceased donor liver allografts were included in the study. The degree of steatosis was assessed by means of conventional liver biopsy as well as HSI, performed at the end of back-table preparation, during normothermic machine perfusion (NMP), and after reperfusion in the recipient., Results: Organ donors were 51 [30-83] years old, and 61.5% were male. Donor body mass index was 24.2 [16.5-38.0] kg/m 2 . The tissue lipid index (TLI) generated by HSI at the end of back-table preparation correlated significantly with the histopathologically assessed degree of overall hepatic steatosis (R2 = .9085, P < .0001); this was based on a correlation of TLI and microvesicular steatosis (R2 = .8120; P < .0001). There is also a linear relationship between the histopathologically assessed degree of overall steatosis and TLI during NMP (R2 = .5646; P = .0031) as well as TLI after reperfusion (R2 = .6562; P = .0008)., Conclusion: HSI may safely be applied for accurate assessment of hepatic steatosis in human liver grafts. Certainly, TLI needs further assessment and validation in larger sample sizes., (© 2022 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

In liver transplantation, older donor age is a well-known risk factor for dismal outcomes, especially due to the high susceptibility of older grafts to ischemia-reperfusion injury. However, whether the factors correlating with impaired graft and patient survival following the transplantation of older grafts follow a linear trend among elderly donors remains elusive. In this study, liver transplantations between January 2006 and May 2018 were analyzed retrospectively. Ninety-two recipients of grafts from donors ≥65 years were identified and divided into two groups: (1) ≥65-69 and (2) ≥ 70 years. One-year patient survival was comparable between recipients of grafts from donors ≥65-69 and ≥70 years (78.9% and 70.0%). One-year graft survival was 73.1% (donor ≥65-69) and 62.5% (donor ≥ 70), while multivariate analysis revealed superior one-year graft survival to be associated with a donor age of ≥65-69. No statistically significant differences were found for rates of primary non-function. The influence of donor age on graft and patient survival appears not to have a distinct impact on dismal outcomes in the range of 65-70 years. The impact of old donor age needs to be balanced with other risk factors, as these donors provide grafts that offer a lifesaving graft function.

The aim of our study was to evaluate hyperspectral imaging (HSI) as a rapid, non-ionizing technique for the assessment of organ quality and the prediction of delayed graft function (DGF) in kidney transplantation after static cold storage (SCS, n = 20), as well as hypothermic machine perfusion (HMP, n = 18). HSI assessment of the kidney parenchyma was performed during organ preservation and at 10 and 30 min after reperfusion using the TIVITA ® Tissue System (Diaspective Vision GmbH, Am Salzhaff, Germany), calculating oxygen saturation (StO 2 ), near-infrared perfusion index (NIR), tissue haemoglobin index (THI), and tissue water index (TWI). Recipient and donor characteristics were comparable between organ preservation groups. Cold ischemic time was significantly longer in the HMP group (14.1 h [3.6-23.1] vs. 8.7h [2.2-17.0], p = 0.002). The overall presence of DGF was comparable between groups (HMP group n = 10 (55.6%), SCS group n = 10 (50.0%)). Prediction of DGF was possible in SCS and HMP kidneys; StO 2 at 10 (50.00 [17.75-76.25] vs. 63.17 [27.00-77.75]%, p = 0.0467) and 30 min (57.63 [18.25-78.25] vs. 65.38 [21.25-83.33]%, p = 0.0323) after reperfusion, as well as NIR at 10 (41.75 [1.0-58.00] vs. 48.63 [12.25-69.50], p = 0.0137) and 30 min (49.63 [8.50-66.75] vs. 55.80 [14.75-73.25], p = 0.0261) after reperfusion were significantly lower in DGF kidneys, independent of the organ preservation method. In conclusion, HSI is a reliable method for intraoperative assessment of renal microperfusion, applicable after organ preservation through SCS and HMP, and predicts the development of DGF.

Purpose: Bariatric surgery is on the rise worldwide. With the desired weight loss after bariatric surgery, patients frequently develop massive skin flaps resulting in the need of abdominoplasty. In these patients, this surgical technique is frequently associated with perioperative complications. Strategies to minimize complications are sought after. The objective of our study was to compare two different dissection techniques and their impact on postoperative outcome., Methods: We included 66 patients in our study who underwent abdominoplasty after massive weight loss following bariatric surgery. In group 1, abdominoplasty was performed using the conventional technique of diathermia (n = 20). In group 2, abdominoplasty was performed using LigaSure Impact™ (n = 46). The duration of the surgical procedure and perioperative complications were recorded as primary endpoints. Secondary endpoints were length of hospital stay and assessment of additional risk factors., Results: Baseline characteristics were comparable between groups. The duration of surgery was significantly shorter in group 2. Postoperative complications were significantly less frequent in group 2 (p = 0.0035). Additional risk factors, e.g., smoking and diabetes mellitus, were not associated with increased rates of perioperative complications., Conclusions: The choice of technical device for dissection in abdominoplasty alone will not guarantee minimized complication rates. Yet, the utilization of LigaSure Impact™ in refined surgical techniques may facilitate reduced rates of complications, especially wound infections, and a shortened duration of surgery., (© 2021. The Author(s).)

Introduction: Hepatocellular carcinoma (HCC) is by far the leading malignant indication for liver transplantation (LT). Few other malignancies, including cholangiocellular carcinoma (CCC), metastases from neuroendocrine tumors (NET), and sarcomas of the liver (LSAR), also are commonly accepted indications for LT. However, there is limited information on their outcome after LT. Methods: Graft and patient survival in 14,623 LTs performed in patients with hepatocellular carcinoma, CCC, NET, and LSAR from 1988 to 2017 and reported to the Collaborative Transplant Study were analyzed. Results: The study group consisted of 13,862 patients who had HCC (94.8%), 498 (3.4%) who had CCC, 100 (0.7%) who had NET, and 163 (1.1%) who had LSAR. CCC patients showed a 5-year graft survival rate of 32.1%, strikingly lower than the 63.2% rate in HCC, 51.6% rate in NET, and 64.5% rate in LSAR patients ( P < 0.001 for all vs. CCC). Multivariable Cox regression analysis revealed a significantly higher risk of graft loss and death due to cancer during the first five post-transplant years in CCC vs. HCC patients (HR 1.77 and 2.56; P < 0.001 for both). The same risks were increased also in NET and LSAR patients but did not reach statistical significance. Conclusion: Among patients with rare malignant indications for LT, CCC patients showed significantly impaired graft as well as patient survival compared to HCC patients. The observed differences might challenge traditional decision-making processes for LT indication and palliative treatment in specific hepatic malignancies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Houben, Schimmack, Unterrainer, Döhler, Mehrabi and Süsal.)

The management of errors and complications makes a significant contribution to the quality assurance of a surgical department. The structured risk management is an integral component of the surgeon's duties that is reflected by the growing relevance of simulation and other training methods employed during medical specialist advanced training. Basic prerequisites for establishing an error culture that aims at improvement of patient safety and the constructive coping with complications, are the removal of taboos and the transparent processing of complicating courses of treatment. Detecting structural and systemic sources of error is preferrable to the application of approaches that focus on individual responsibility, e.g. shame and blame. There are numerous validated tools available for the prevention, recognition and successful treatment of complications. Team time out protocols for circumventing fatal errors, standardized operating procedures and morbidity and mortality conferences are the most important measures for ensuring patient safety. The standardized, consistent and interdisciplinary handling of unavoidable complications according to the failure to rescue concept is pivotal for the prevention of a fatal course.

BACKGROUND Although most centers perform primary portal vein reperfusion (PV) in orthotopic liver transplantation (OLT) for historical reasons, there is so far no sound evidence as to whether this technique is superior. The present study evaluated the long-term outcome of 3 different reperfusion sequences: PV vs primary arterial (A) vs simultaneous reperfusion (SIM). MATERIAL AND METHODS All patients at our center who underwent OLT (who received a primary, whole-organ liver graft) from 2006 to 2007 were evaluated for analysis. RESULTS A total of 61 patients were found eligible (PV: 25, A: 22, SIM: 14). Twenty-one patients (35%) were still alive after the follow-up period of 12 years. Despite poorer starting conditions such as higher recipient age (59 y (SIM) vs 55 y (A) vs 50 y (PV), P=0.01) and donor age (56 y (SIM) vs 51 y (PV) vs 50 y (A), n.s.), higher MELD scores (22 vs 19 (PV) vs 17 (A), n.s.), as well as a higher number of marginal donor organs (79% (SIM) vs 36% (A/PV), P=0.02), SIM-recipients demonstrated superior outcomes. Overall survival was 8.1 y (SIM), 4.8 y (PV), and 5.9 y (A, n.s.)). None of the SIM-recipients underwent re-transplantation, while the rate was 32% in the PV-group. The 8.1 y graft survival in SIM-recipients was significantly longer than in the other 2 groups, which were 3.3 y (PV) and 5.5 y (A, P=0.013). CONCLUSIONS Although SIM-reperfused recipients were the oldest and received grafts of inferior quality, these recipients showed superior results in terms of overall patient and graft survival. Multicentric randomized controlled trials with larger study populations are required to confirm this finding.

Background: Despite steadily increasing donor age, there are no general guidelines for the use of organs from elderly donors in liver transplantation. This study focuses on identifying the recipients who are less affected from an old-donor organ graft and conversely in whom a rather unfavorable outcome is expected because of high donor age., Methods: Forty-eight thousand two hundred sixty-one adult liver transplantations, performed between 2000 and 2017 and reported to the Collaborative Transplant Study, were analyzed., Results: The proportion of ≥65-year-old donors has risen to >33% in recent years. The donor age has an approximately linear influence on graft survival. On average, each year's rise in the donor age was associated with a 0.9% increase in the risk of graft loss (hazard ratio [HR], 1.009; P < 0.001). The impact of donor age was strong in patients with hepatitis C-related cirrhosis (HR, 1.013; P < 0.001), substantial in patients with alcoholic cirrhosis (HR, 1.007; P < 0.001) and rather weak in patients with hepatocellular carcinoma (HR, 1.003; P = 0.038). The increase in the risk of graft loss per year rise in donor age was 1.4% for 18 to 49 year olds, 1.0% for middle-aged, and only 0.4% for ≥60-year-old recipients (all P < 0.001)., Conclusions: Consequently, older recipients and especially patients with hepatocellular carcinoma seem to be less affected by an increased donor age, whereas the donor age is an important factor in all other patient groups.

Background: Organ preservation before transplantation is still a challenge. Both the University of Wisconsin and Bretschneider's histidine-tryptophan-ketoglutarate (HTK; Custodiol®) solution are standard for liver, kidney and pancreas preservation. Organ preservation with both solutions is comparable; recently, however, Custodiol® solution has been modified to Custodiol-N according to the needs of today. Thus, our study was defined to study its effect in clinical transplantation., Methods: Patients undergoing kidney transplantation (n = 412) (including approximately 30 combined kidney-pancreas) or liver transplantation (n = 202) receive grafts that have been cold stored in either Custodiol® or Custodiol-N to demonstrate noninferiority of Custodiol-N regarding both graft function and graft injury after transplantation., Discussion: Preclinical data have clearly shown that Custodiol-N is superior to Custodiol® in cold static organ preservation via mechanisms including inhibition of hypoxic cell injury, cold-induced cell injury and avoidance of adverse effects during warm exposure to the solution. Further clinical safety data on Custodiol-N for cardioplegia are available. Thus, this study was designed to compare Custodiol® with Custodiol-N for the first time in a prospective, randomized, single-blinded, multicentre, phase III clinical transplantation trial., Trial Registration: Eudra-CT, 2017-002198-20. Registered on 28 November 2018.

Background and Aims: Transient elastography (TE) has routinely been implemented in the diagnosis and assessment of chronic liver disease. Little data are available in the post liver transplant (LTx) setting., Methods: Three months after LTx, we performed TE in 137 liver transplant recipients and investigated its predictive value upon further clinical outcome. The mean follow-up time for clinical outcome was 24 months., Results: Mean TE value was 10.6 kPa (± 6.3 kPa; range 2.8 - 29.9 kPa). There was a significant correlation between TE and aspartate aminotransferase (AST) (p=0.004), gamma-glutamyl transferase (GGT) (p=0.031) and bilirubin (p<0.001) serum levels. In Cox univariate analysis, TE served as a predictor of actuarial survival free of liver transplantation (OR=1.111, 95%CI: 1.051-1.174; p<0.001). In multivariate analysis, TE remained an independent risk factor associated with reduced actuarial survival free of liver transplantation (OR=1.080, 95%CI: 1.001-1.166; p=0.047), along with thrombocytes (OR=0.992, 95%CI: 0.986-0.999; p=0.020) and metabolic co-disease (OR = 0.250, 95%CI: 0.070-0.895; p=0.033)., Conclusion: Transient elastography measurement at three months after LTx seems a robust predictor of survival in liver transplant recipients.

Background: Multidrug-resistant (MDR) pathogens represent an emerging challenge in end-stage liver disease and in liver transplant recipients., Methods: We evaluated the impact of MDR bacteria upon clinical outcomes in patients with end-stage liver disease (n = 777) at the time of enrollment on the liver transplant (LTx) waiting list, after first LTx (n = 645), and after second LTx (n = 128)., Results: Colonization/infection with MDR bacteria was present in 72/777 patients on the waiting list, in 98/645 patients at first LTx, and in 46/128 patients at second LTx. While on the LTx waiting list, the time until first hydropic decompensation (p = 0.021), hepatic encephalopathy (p < 0.001) and hepatorenal syndrome (p < 0.001) was reduced in the presence of MDR bacteria, which remained an independent risk factor of poor survival in multivariate analysis (p < 0.001). Following first and second liver transplant, MDR bacteria were associated with an increased risk of infection-related deaths (first LTx: p < 0.001; second LTx: p = 0.037) and reduced actuarial survival (first LTx: p < 0.001; second LTx: p = 0.046)., Conclusions: We showed that MDR pathogens are associated with poor outcomes before, after first and after recurrent LTx.

Background: Extended liver resections still bear the risk of severe haemorrhage. Moreover, the amount of blood loss during liver resection determines the need for perioperative blood transfusions and is of prognostic relevance in oncologic surgery. Even though there is an ongoing debate about its effectiveness and tolerable duration, the Pringle Maneuver (PM) as an occlusion of the hepatic inflow is routinely applied to reduce blood loss during parenchymal dissection. In combination with the stapler resection technique, PM is expected to minimize blood loss during major liver resection safely due to the short parenchymal dissection duration., Methods: In a single center prospective, randomized, controlled, parallel, confirmatory trial the combination of PM and stapler resection technique in patients undergoing right and left hepatectomies will be tested against the control group that applies stapler resection without the use of PM. The primary endpoint of the study is the total intraoperative blood loss. The measurement of the intraoperative blood loss is conducted with respect to all handled rinse fluids during surgery and by weighing used swabs to generate accurate and comparable data. Secondary endpoints include intra- and postoperative blood transfusion requirements, liver function parameters and the 90-day mortality rate. A sample size of fifty-three patients in either group was calculated to detect a clinically significant difference in blood loss of at least 450 ml with an α of 5% at 80% power. The individual follow-up will be 90 days., Discussion: This is the first clinical trial to test the combination of PM and stapler resection technique as a means to reduce intraoperative blood loss in hepatic left or right resection. Given the short parenchymal dissection duration in stapler resection, PM is expected to be applied shortly without compromising liver function postoperatively., Trial Registration: The PriMaL StHep trial has been prospectively registered to the German Clinical Trial Registry (WHO ID: DRKS00010427 ) on April 21st. 2016.

Background: The surgical technique used in liver transplantation has undergone constant evolution in an effort to develop a safe, highly standardized procedure. Despite this, the initial step of recipient hepatectomy has not been the focus of clinical research thus far. Due to advanced coagulopathy in liver transplant recipients, this part of the operation still carries the risk of severe hemorrhage. This trial is designed to compare an electrothermal bipolar vessel sealing device (LigaSure™) and an ultrasound dissector (HARMONIC ACE®+7) with standard surgical techniques during the recipients' hepatectomy in liver transplantation., Methods/design: In a single-center, prospective, randomized, controlled, parallel, three-armed, confirmatory, open trial, LigaSure™ and HARMONIC ACE®+7 will be compared with standard surgical techniques that use titanium clips and conventional knot-tying ligations during recipient hepatectomy in liver transplantation. Intraoperative total blood loss is the primary endpoint of the trial. Secondary endpoints include blood loss during hepatectomy, the duration of both the hepatectomy and the entire surgical procedure, and blood transfusion requirements of the procedure. To generate reliable data, intraoperative blood loss will be recorded with respect to all rinse fluids during surgery, ascites, and by weighing used swabs. At 80% power and an alpha of 0.025 for both of the experimental groups, 23 subjects will be analyzed per protocol in each study arm in order to detect clinically relevant reduction of intraoperative blood loss. The intention-to-treat analysis will include 69 patients. The follow-up period for each patient will be 90 days for safety reasons, whereas all clinical outcomes will be measured within the first 10 postoperative days., Discussion: To our knowledge, this is the first prospective, randomized trial comparing two innovative technical methods of vessel sealing and dissection with standard techniques for recipient hepatectomy. This will be done to detect relevant reduction of intraoperative blood loss during liver transplant. The results of the trial are expected to improve patient outcome and safety after liver transplant and to increase the general safety of this procedure., Trial Registration: ClinicalTrials.gov, NCT 03323242 . Registered on October 26, 2017.

BACKGROUND Pre-transplant assessment of the graft for liver transplantation is crucial. Based on experimental data, this study was designed to assess both nuclear high mobility group box-1 (HMGB-1) protein and arginine-specific proteolytic activity (ASPA) in the graft effluent. MATERIAL AND METHODS In a non-interventional trial, both HMGB-1 and ASPA were measured in the effluent of 30 liver grafts after cold storage before transplantation. Values of HMGB-1 and ASPA levels were compared with established prognostic parameters such as the donor risk index, balance of risk score, and Donor-Model for End-Stage Liver Disease. RESULTS The early allograft dysfunction (EAD) was best predicted by recipient age (p=0.026) and HMGB-1 (p=0.031). HMGB -1 thresholds indicated the likelihood for initial non-function (1608 ng/ml, p=0.004) and EAD (580 ng/ml, p=0.017). The multivariate binary regression analysis showed a 21-fold higher (95% CI: 1.6-284.5, p=0.022) risk for EAD in cases with levels exceeding 580 ng/ml. The ASPA was lower in cases of initial non-function (p=0.028) but did not correlate with the rate of EAD (p=0.4). CONCLUSIONS This study demonstrates the feasibility of HMGB-1 detection in the graft effluent after cold storage. Along with conventional prognostic scores, it may be helpful to predict the early fate of a graft in human liver transplantation.

Background According to Good Clinical Practice, clinical trials must protect rights and safety of patients and make sure that the trial results are valid and interpretable. Monitoring on-site has an important role in achieving these objectives; it controls trial conduct at trial sites and informs the sponsor on systematic problems. In the past, extensive on-site monitoring with a particular focus on formal source data verification often lost sight of systematic problems in study procedures that endanger Good Clinical Practice objectives. ADAMON is a prospective, stratified, cluster-randomised, controlled study comparing extensive on-site monitoring with risk-adapted monitoring according to a previously published approach. Methods In all, 213 sites from 11 academic trials were cluster-randomised between extensive on-site monitoring (104) and risk-adapted monitoring (109). Independent post-trial audits using structured manuals were performed to determine the frequency of major Good Clinical Practice findings at the patient level. The primary outcome measure is the proportion of audited patients with at least one major audit finding. Analysis relies on logistic regression incorporating trial and monitoring arm as fixed effects and site as random effect. The hypothesis was that risk-adapted monitoring is non-inferior to extensive on-site monitoring with a non-inferiority margin of 0.60 (logit scale). Results Average number of monitoring visits and time spent on-site was 2.1 and 2.7 times higher in extensive on-site monitoring than in risk-adapted monitoring, respectively. A total of 156 (extensive on-site monitoring: 76; risk-adapted monitoring: 80) sites were audited. In 996 of 1618 audited patients, a total of 2456 major audit findings were documented. Depending on the trial, findings were identified in 18%-99% of the audited patients, with no marked monitoring effect in any of the trials. The estimated monitoring effect is -0.04 on the logit scale with two-sided 95% confidence interval (-0.40; 0.33), demonstrating that risk-adapted monitoring is non-inferior to extensive on-site monitoring. At most, extensive on-site monitoring could reduce the frequency of major Good Clinical Practice findings by 8.2% compared with risk-adapted monitoring. Conclusion Compared with risk-adapted monitoring, the potential benefit of extensive on-site monitoring is small relative to overall finding rates, although risk-adapted monitoring requires less than 50% of extensive on-site monitoring resources. Clusters of findings within trials suggest that complicated, overly specific or not properly justified protocol requirements contributed to the overall frequency of findings. Risk-adapted monitoring in only a sample of patients appears sufficient to identify systematic problems in the conduct of clinical trials. Risk-adapted monitoring has a part to play in quality control. However, no monitoring strategy can remedy defects in quality of design. Monitoring should be embedded in a comprehensive quality management approach covering the entire trial lifecycle.

Deciphering the genetic control of flowering and ripening periods in apple is essential for breeding cultivars adapted to their growing environments. We implemented a large Genome-Wide Association Study (GWAS) at the European level using an association panel of 1,168 different apple genotypes distributed over six locations and phenotyped for these phenological traits. The panel was genotyped at a high-density of SNPs using the Axiom®Apple 480 K SNP array. We ran GWAS with a multi-locus mixed model (MLMM), which handles the putatively confounding effect of significant SNPs elsewhere on the genome. Genomic regions were further investigated to reveal candidate genes responsible for the phenotypic variation. At the whole population level, GWAS retained two SNPs as cofactors on chromosome 9 for flowering period, and six for ripening period (four on chromosome 3, one on chromosome 10 and one on chromosome 16) which, together accounted for 8.9 and 17.2% of the phenotypic variance, respectively. For both traits, SNPs in weak linkage disequilibrium were detected nearby, thus suggesting the existence of allelic heterogeneity. The geographic origins and relationships of apple cultivars accounted for large parts of the phenotypic variation. Variation in genotypic frequency of the SNPs associated with the two traits was connected to the geographic origin of the genotypes (grouped as North+East, West and South Europe), and indicated differential selection in different growing environments. Genes encoding transcription factors containing either NAC or MADS domains were identified as major candidates within the small confidence intervals computed for the associated genomic regions. A strong microsynteny between apple and peach was revealed in all the four confidence interval regions. This study shows how association genetics can unravel the genetic control of important horticultural traits in apple, as well as reduce the confidence intervals of the associated regions identified by linkage mapping approaches. Our findings can be used for the improvement of apple through marker-assisted breeding strategies that take advantage of the accumulating additive effects of the identified SNPs.

Background: The amount and structure of genetic diversity in dessert apple germplasm conserved at a European level is mostly unknown, since all diversity studies conducted in Europe until now have been performed on regional or national collections. Here, we applied a common set of 16 SSR markers to genotype more than 2,400 accessions across 14 collections representing three broad European geographic regions (North + East, West and South) with the aim to analyze the extent, distribution and structure of variation in the apple genetic resources in Europe., Results: A Bayesian model-based clustering approach showed that diversity was organized in three groups, although these were only moderately differentiated (FST = 0.031). A nested Bayesian clustering approach allowed identification of subgroups which revealed internal patterns of substructure within the groups, allowing a finer delineation of the variation into eight subgroups (FST = 0.044). The first level of stratification revealed an asymmetric division of the germplasm among the three groups, and a clear association was found with the geographical regions of origin of the cultivars. The substructure revealed clear partitioning of genetic groups among countries, but also interesting associations between subgroups and breeding purposes of recent cultivars or particular usage such as cider production. Additional parentage analyses allowed us to identify both putative parents of more than 40 old and/or local cultivars giving interesting insights in the pedigree of some emblematic cultivars., Conclusions: The variation found at group and subgroup levels may reflect a combination of historical processes of migration/selection and adaptive factors to diverse agricultural environments that, together with genetic drift, have resulted in extensive genetic variation but limited population structure. The European dessert apple germplasm represents an important source of genetic diversity with a strong historical and patrimonial value. The present work thus constitutes a decisive step in the field of conservation genetics. Moreover, the obtained data can be used for defining a European apple core collection useful for further identification of genomic regions associated with commercially important horticultural traits in apple through genome-wide association studies.

Graft rinse prior reperfusion in liver transplantation (LT) is believed to reduce the incidence of postreperfusion syndrome and improve clinical outcome. A MEDLINE search was performed to obtain a comprehensive review of the published literature dealing with graft rinse in LT. Moreover, all thirty-four LT centers in the Eurotransplant (ET) region were invited to participate in an online survey to whether or not graft rinse is performed and whether further research in the field is needed. Seventeen reports have been found to investigate graft rinse protocols in 1894 LT recipients. Eighteen of the thirty centers that participated in the online survey performed graft rinse prior reperfusion in LT. The most commonly used rinse solution was albumin. Nineteen centers stated interest in participating in a multicenter RCT in the field. The published literature does not provide concluding appraisal of the benefit of graft rinse in LT. Graft rinse protocols are not standardized and are based on personal experience. Appropriately designed clinical trials addressing the topic are demanded. The online survey appears to be a helpful tool for the evaluation of clinical practice and future research topics in the transplant community., (© 2015 Steunstichting ESOT.)

Background: Although animal studies models are frequently used for the purpose of attenuating ischemia reperfusion injury (IRI) in liver transplantation (LT), many of pharmacological agents have not become part of clinical routine., Methods: A search was performed using the PubMed database to identify agents, from which 58 articles containing 2700 rat LT procedures were selected. The identified pharmacological agents were categorized as follows: I - adenosine agonists, nitric oxide agonists, endothelin antagonists, and prostaglandins, II - Kupffer cell inactivator, III - complement inhibiter, IV - antioxidant, V - neutrophil inactivator, VI -anti-apoptosis agent, VII - heat shock protein and nuclear factor kappa B inducer, VIII - metabolic agent, IX - traditional Chinese medicine, and X - others. Meta-analysis using 7-day-survival rate was also performed with Mantel-Haenszel's Random effects model., Results: The categorization revealed that the rate of donor-treated experiments in each group was highest for agents from Group II (70%) and VII (71%), whereas it was higher for agents from Group V (83%) in the recipient-treated experiments. Furthermore, 90% of the experiments with agents in Group II provided 7-day-survival benefits. The Risk Ratio (RR) of the meta-analysis was 2.43 [95% CI: 1.88-3.14] with moderate heterogeneity. However, the RR of each of the studies was too model-dependent to be used in the search for the most promising pharmacological agent., Conclusion: With regard to hepatic IRI pathology, the categorization of agents of interest would be a first step in designing suitable multifactorial and pleiotropic approaches to develop pharmacological strategies.

The interdisciplinary management of postoperative complications in liver transplantation is of extreme importance. Due to organ shortage and prioritization of the most severely ill recipients in the model for end-stage liver disease (MELD)-based allocation, both donor and recipient associated morbidity are increasing. An interdisciplinary, structured monitoring concept is essential for the timely identification and specific treatment of postoperative complications. Interdisciplinary clinical rounds, laboratory testing and Doppler ultrasound monitoring of the graft perfusion are as important as comprehensive anti-infection prophylaxis and immunosuppression. Arterial perfusion disorders of any kind, biliary complications and postoperative fluid accumulation demand individualized therapeutic concepts. In summary, the success of liver transplantation depends on the communication and coordinated interdisciplinary cooperation of all disciplines involved.

Background: MELD-based allocation for liver transplantation follows the "sickest-patient-first" strategy. The latter patients present with both, decreased immune competence and poor kidney function which is further impaired by immunosuppressants., Methods/design: In this prospective observational study, 50 patients with de novo low-dose standard Advagraf®-based immunosuppression consisting of Advagraf®, Mycophenolat-mofetil and Corticosteroids after liver transplantation will be evaluated. Advagraf® trough levels of 7-10 μg/l will be reached at the end of the first postoperative week. Immunostatus, infectious complications, graft and kidney function are compared between patients with a pretransplant calculated MELD-score of ≤20 and >20. Each group comprises of 25 consecutive patients. Prior to liver transplantation and on the postoperative days 1, 3 and 7, the patients' graft function (LiMAx test) will be evaluated. On the postoperative days 3, 5 and 7 the patients' immune status will be evaluated by the measurement of their monocytic HLA-DR status.Infectious complications (CMV-reactivation, wound infection, urinary tract infection, and pneumonia), graft- and kidney function will be analysed on day 0, within the first week, and 1, 3, 6, 9 and 12 months after liver transplantation., Discussion: This study was designed to assess the effect of a standard low-dose Calcineurin inhibitor-based immunosuppression regime with Advagraf® on the rate of infectious complications, graft and renal function after liver transplantation., Trial Registration: The trial is registered at "Clinical Trials" (http://www.clinicaltrials.gov), NCT01781195.

Background: Pancreatic ductal adenocarcinoma (PDA) is one of the most aggressive malignancies with marked resistance to chemo- and radiotherapy. PDA-cancer stem cells (CSCs) are not targeted by current therapies and may be a reason for poor prognosis. Studies indicate that diets rich in cabbage, broccoli, and cauliflower offer cancer preventative and therapeutic benefits. Recent experimental studies have confirmed these findings and demonstrated that isothiocyanate, sulforaphane, and the polyphenol, quercetin, effectively reduced tumor growth and enhanced the sensitivity of the cancer cells to current chemotherapeutics. The aim of the present study is to test the feasibility of a randomized controlled trial on the application of freeze-dried broccoli sprouts in patients with advanced PDA., Methods and Study Design: The study is designed as a prospective randomized, double-blinded pilot trial with a treatment and a placebo-controlled arm in a single center setting. A total number of forty patients (18 years or older) in two parallel groups with advanced, surgically non-resectable PDA under palliative chemotherapy are planned for recruitment. Patients in the treatment group will receive fifteen capsules of the study substance per day (90 mg of active sulforaphane) during the chemotherapy treatment course. Patients in the placebo group will receive the same capsule size and portion distribution with inactive substances (mainly methylcellulose). The follow-up duration is one year. Feasibility of the study substance, adverse effects, and patient compliance, as well as levels of serum tumor markers (CEA, CA 19-9), quality of life, and patient overall survival rates will be assessed at defined points of time., Discussion: The POUDER trial is expected to transfer promising experimental and epidemiological data into a clinical pilot study to assess the effectiveness of broccoli sprout extracts in the treatment of advanced PDA. The study objectives will provide data on the clinical feasibility and acceptability of a supportive treatment option accompanying palliative chemotherapy. Based on these results, future clinical studies to create further evidence in this field are possible., Trial Registration: The POUDER trial has been registered at ClinicalTrials.gov with an ID NCT01879878 and WHO with an ID U1111-1144-2013 on June 13th 2013.

Everolimus is an orally administrated mammalian target of rapamycin (mTOR) inhibitor. Several large-scale randomized controlled trials (RCTs) have demonstrated the survival benefits of everolimus at the dose of 10 mg/day for solid cancers. Furthermore, mTOR-inhibitor-based immunosuppression is associated with survival benefits for patients with hepatocellular carcinoma (HCC) who have received liver transplantation. However, a low rate of tumor reduction and some adverse events have been pointed out. This review summarizes the antitumor effects and adverse events of everolimus and evaluates its possible application in advanced HCC. For the meta-analysis of adverse events, we used the RCTs for solid cancers. The odds ratios of adverse events were calculated using the Peto method. Manypreclinical studies demonstrated that everolimus had antitumor effects such as antiproliferation and antiangiogenesis. However, some differences in the effects were observed among in vivo animal studies for HCC treatment. Meanwhile, clinical studies demonstrated that the response rate of single-agent everolimus was low, though survival benefits could be expected. The meta-analysis revealed the odds ratios (95% confidence interval [CI]) of stomatitis: 5.42 [4.31-6.73], hyperglycemia: 3.22 [2.37-4.39], anemia: 3.34 [2.37-4.67], pneumonitis: 6.02 [3.95-9.16], aspartate aminotransferase levels: 2.22 [1.37-3.62], and serum alanine aminotransferase levels: 2.94 [1.72-5.02], respectively. Everolimus at the dose of 10 mg/day significantly increased the risk of the adverse events. In order to enable its application to the standard conventional therapies of HCC, further studies are required to enhance the antitumor effects and manage the adverse events of everolimus., (© 2013 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Immune-mediated hemolysis is not included in the list of adverse reactions related to contrast medium (CM). Here, we report on a patient who developed immune hemolytic anemia (IHA) related to iomeprol, a nonionic CM., Study Design and Methods: A 34-year-old female patient developed massive hemolysis during infusion of 50 mL of iomeprol. Serologic studies were performed using standard techniques., Results: Before hemolysis, the patient's serum was weakly positive with e+ red blood cells (RBCs; autoanti-e) and the direct antiglobulin test (DAT) was negative. After hemolysis, the patient's serum samples became significantly reactive with e- RBCs in the presence of iomeprol but not in the presence of two other similar CM. The DAT became strongly positive only with anti-C3d., Conclusion: Initially, an allergic reaction was suggested, and as the hemolysis became obvious, a toxic hemolysis was suspected. However, serologic reexamination revealed an iomeprol-dependent antibody. IHA related to CM has yet only been described in one patient in 1991. The hemolysis in that patient was related to Isopaque, an older ionic CM. Here, we describe an additional patient and recommend that CM should be considered as a rare risk in the development of IHA., (© 2013 American Association of Blood Banks.)

It remains unclear which liver graft reperfusion technique leads to the best outcome following transplantation. An online survey was sent to all transplant centres (n = 37) within Eurotransplant (ET) to collect information on their technique used for reperfusion of liver grafts. Furthermore, a systematic review of all literature was performed and a meta-analysis was conducted based on patients' mortality, number of retransplantations and incidence of biliary complications, depending on the technique used. Of the 28 evaluated centres, 11 (39%) reported performing simultaneous reperfusion (SIMR), 13 (46%) perform initial portal vein reperfusion (IPR), 1 (4%) performs an initial hepatic artery reperfusion (IAR) and 3 (11%) perform retrograde reperfusion (RETR). In 21 centres (75%), one reperfusion technique is used as a standard, but in only one centre is this decision based on available literature. Twenty centres (71%) said they would agree to participate in randomized controlled trials (RCT) if required. For meta-analysis, IAR vs. IPR, SIMR vs. IPR and RETR vs. IPR were compared. There was no difference between any of the techniques compared. There is no consensus on a preferable reperfusion technique. Available evidence does not help in the decision-making process. There is thus an urgent need for multicentric RCTs., (© 2013 The Authors Transplant International © 2013 European Society for Organ Transplantation. Published by Blackwell Publishing Ltd.)

The plant family Brassicaceae, formerly Cruciferae, contains mustard oil glycosides, from which mustard oils are enzymatically hydrolyzed. Mustard oils offer protection from pests, microorganisms and fungi. More than 120 different mustard oils with various biological functions are known. Since ancient times, these substances are used as natural antibiotics, antiviral drugs and antimycotics. The antioxidative effect of mustard oils contributes to protection from DNA damage. Epidemiological and experimental studies have shown preventive and therapeutic effects of crucifers or isolated substances thereof. Particularly well studied is the mustard oil sulforaphane, which is contained in high concentrations in broccoli and its sprouts. As has been shown in mice recently, sulforaphane also targets the most malignant cancer stem cells, which are not affected by conventional cancer treatments. Based on these promising results, the first prospective clinical studies with cancer patients and sulforaphane-enriched broccoli sprouts have now been initiated in the United States.

As part of oncologic visceral surgical operations the surgeon is confronted with anatomical barriers. In particular abdominal sarcomas and carcinomas sometimes require a vascular surgical procedure in order to achieve a radical and curative treatment. By using vascular surgical techniques there is the possibility for oncology patients to expand the boundaries of operability and to allow a long tumor-free survival. For each affected arterial and venous structure there are special reconstruction methods which require an optimal vascular graft. The aim of vascular resection and reconstruction should focus not only on the radicality of the operation but should also take the optimal circulation recovery of blood in the tumor resected area into account.

We measure the charge asymmetry A ≡ (N++ - N--)/(N++ + N--) of like-sign dimuon events in 6.1 fb-1 of pp collisions recorded with the D0 detector at a center-of-mass energy square root(s) = 1.96   TeV at the Fermilab Tevatron collider. From A we extract the like-sign dimuon charge asymmetry in semileptonic b-hadron decays: A(sl)(b) = -0.009 57 ± 0.002 51(stat) ± 0.001 46(sys). It differs by 3.2 standard deviations from the standard model prediction A(sl)(b)(SM) = (-2.3(-0.6)(+0.5)) × 10(-4), and provides first evidence of anomalous CP violation in the mixing of neutral B mesons.

Background: Benefit of adding amantadine to antiviral therapy for hepatitis C is controversial., Aims: We aimed to examine whether such policy enhances sustained viral response in treatment-naïve patients., Methods: 297 naïve hepatitis C patients were randomized for treatment with amantadine 200mg or placebo, combined with weight-based ribavirin and 12-day high-dose interferon alpha-2b induction therapy, followed by PEG-interferon alpha-2b (1.5 microg/kg/week up to 26 weeks and thereafter, 1.0 microg/kg/week until week 52). Treatment was discontinued if hepatitis C virus (HCV) RNA was positive at week 24., Results: 49% of patients were (former) drug users. Genotype 1 occurred in 45%, high viral load in 70% and severe fibrosis/cirrhosis in 32%, without differences between amantadine or placebo groups. 90 patients prematurely discontinued treatment, mainly because of grade 3 or 4 toxicity. Intention-to-treat analysis revealed sustained viral response in 47% and 51% of amantadine and placebo groups (p=0.49). Amantadine did not enhance sustained viral response in patients with genotype 1 or high viral load nor did it improve primary non-response, breakthrough or relapse rates. Genotype non-1 and lower pre-treatment gamma GT levels were independent predictors for sustained viral response., Conclusion: Adding amantadine to antiviral therapy of previously untreated chronic hepatitis C patients has no beneficial effects., ((c) 2009 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Using 5.4  fb(-1) of integrated luminosity from pp collisions at square root(s)=1.96  TeV collected by the D0 detector at the Fermilab Tevatron Collider, we search for decays of the lightest Kaluza-Klein mode of the graviton in the Randall-Sundrum model to ee and γγ. We set 95% C.L. lower limits on the mass of the lightest graviton between 560 and 1050 GeV for values of the coupling k/M(Pl) between 0.01 and 0.1.

Objective: Although 'gut feelings' are perceived as playing a substantial role in the diagnostic reasoning of the general practitioner (GP), there is little evidence about their diagnostic and prognostic value. Consensus on both types of 'gut feelings' (a 'sense of alarm', a 'sense of reassurance') has enabled us to operationalize the concept. As a next step we wanted to identify research questions that are considered relevant to validate the concept of 'gut feelings' and to estimate its usefulness for daily practice and medical education. Moreover, we were interested in the study designs considered appropriate to study these research questions., Methods: The nominal group technique (NGT) is a qualitative research method of judgmental decision-making involving four phases: generating ideas, recording them, evaluation and prioritization. Dutch and Belgian academics whose subject is general practice (n = 18), attended one of three meetings during which NGT was used to produce a 'research agenda' on 'gut feelings'., Results: NGT yielded ten research questions and nine corresponding appropriate designs on four topics, i.e. the diagnostic value of 'gut feelings', the validation of its determinants, the opportunities for integrating 'gut feelings' in medical education and a rest group. The study designs respectively included recording and follow-up of 'gut feelings', video recording of consultations with stimulated recall using simulated and real patients respectively, analysing trainees' consultation stories and videos, linguistic analyses, and vignette studies. Furthermore, two experimental designs were proposed., Conclusion: A European research agenda on 'gut feelings' in general practice has been established and could be used in collaborative research.

We report results from a search for production of a neutral Higgs boson in association with a b quark. We search for Higgs decays to tau pairs with one tau subsequently decaying to a muon and the other to hadrons. The data correspond to 2.7 fb(-1) of pp collisions recorded by the D0 detector at square root(s)=1.96 TeV. The data are found to be consistent with background predictions. The result allows us to exclude a significant region of parameter space of the minimal supersymmetric model.

A search is performed for the standard model Higgs boson in 5.2 fb{-1} of pp collisions at sqrt[s]=1.96 TeV, collected with the D0 detector at the Fermilab Tevatron Collider. The final state considered is a pair of b jets and large missing transverse energy, as expected from pp-->ZH-->nunubb production. The search is also sensitive to the WH-->lnubb channel when the charged lepton is not identified. For a Higgs boson mass of 115 GeV, a limit is set at the 95% C.L. on the cross section multiplied by branching fraction for [pp-->(Z/W)H](H-->bb) that is a factor of 3.7 larger than the standard model value, consistent with the factor of 4.6 expected.

We present the first search for an electrically charged resonance W' decaying to a WZ boson pair using 4.1 fb(-1) of integrated luminosity collected with the D0 detector at the Fermilab Tevatron pp collider. The WZ pairs are reconstructed through their decays into three charged leptons (l=e, mu). A total of 9 data events is observed in good agreement with the background prediction. We set 95% C.L. limits on the W'WZ coupling and on the W' production cross section multiplied by the branching fractions. We also exclude W' masses between 188 and 520 GeV within a simple extension of the standard model and set the most restrictive limits to date on low-scale technicolor models.

A search for the standard model Higgs boson is presented using events with two charged leptons and large missing transverse energy selected from 5.4 fb(-1) of integrated luminosity in pp collisions at square root(s) = 1.96 TeV collected with the D0 detector at the Fermilab Tevatron collider. No significant excess of events above background predictions is found, and observed (expected) upper limits at 95% confidence level on the rate of Higgs boson production are derived that are a factor of 1.55 (1.36) above the predicted standard model cross section at m(H) = 165 GeV.

We combine searches by the CDF and D0 Collaborations for a Higgs boson decaying to W+W-. The data correspond to an integrated total luminosity of 4.8 (CDF) and 5.4 (D0) fb(-1) of pp collisions at square root(s) = 1.96 TeV at the Fermilab Tevatron collider. No excess is observed above background expectation, and resulting limits on Higgs boson production exclude a standard model Higgs boson in the mass range 162-166 GeV at the 95% C.L.

We present a direct measurement of the width of the W boson using the shape of the transverse mass distribution of W --> enu candidate events. Data from approximately 1 fb(-1) of integrated luminosity recorded at square root of s = 1.96 TeV by the D0 detector at the Fermilab Tevatron pp collider are analyzed. We use the same methods and data sample that were used for our recently published W boson mass measurement, except for the modeling of the recoil, which is done with a new method based on a recoil library. Our result, 2.028 +/- 0.072 GeV, is in agreement with the predictions of the standard model.