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Social Prescribing originated in the United Kingdom. However, it is interesting for other European countries because it builds upon existing structures in health and social care. Thus, the German Federal Ministry of Education and Research (BMBF) sponsored a systematic review on social prescribing covering studies worldwide. A systematic review on the effect of social prescribing was conducted with a search of eleven databases. Included were interventional studies which targeted at adults with a community referral initiated by a medical provider. This presentation will focus on methodological aspects of the studies found. Four main challenges in reviewing the evidence of social prescribing were found: the heterogeneity of outcomes, the origin of a majority of studies from a single health care system, the lack of randomized controlled trials, and an often insufficient reporting. 1) Heterogeneity of outcomes: The outcome measurements cover most often the quality of life, mental health and health economics. Follow-up time was often short; 2) Uniformity of health care setting: Out of 52 studies included, 50 took place in the UK and two in Australia; 3) Lack of randomized trials: Out of the 52 studies, only two were randomized controlled trials, one was a nonrandomized controlled trial and 49 studies were noncontrolled studies with a before-and-after design; 4) Most of the studies have not been published in peer reviewed journals, but in openly available reports. Only 16 studies were published fully peer-reviewed, and four partly peer reviewed. Often, important results were missing in the reports. The existing evidence on social prescribing is mainly from one health care system and of mainly low quality. This is a barrier to implementing social prescribing schemes in other countries. Thus, rigorous randomized controlled trials on social prescribing, especially from health care systems outside the UK, are needed to ascertain the efficacy of social prescribing. [ABSTRACT FROM AUTHOR]

Background: Emergency departments (EDs) are frequently overcrowded and increasingly used by nonurgent patients. Symptom checkers (SCs) offer on-demand access to disease suggestions and recommended actions, potentially improving overall patient flow. Contrary to the increasing use of SCs, there is a lack of supporting evidence based on direct patient use., Objective: This study aimed to compare the diagnostic accuracy, safety, usability, and acceptance of 2 SCs, Ada and Symptoma., Methods: A randomized, crossover, head-to-head, double-blinded study including consecutive adult patients presenting to the ED at University Hospital Erlangen. Patients completed both SCs, Ada and Symptoma. The primary outcome was the diagnostic accuracy of SCs. In total, 6 blinded independent expert raters classified diagnostic concordance of SC suggestions with the final discharge diagnosis as (1) identical, (2) plausible, or (3) diagnostically different. SC suggestions per patient were additionally classified as safe or potentially life-threatening, and the concordance of Ada's and physician-based triage category was assessed. Secondary outcomes were SC usability (5-point Likert-scale: 1=very easy to use to 5=very difficult to use) and SC acceptance net promoter score (NPS)., Results: A total of 450 patients completed the study between April and November 2021. The most common chief complaint was chest pain (160/437, 37%). The identical diagnosis was ranked first (or within the top 5 diagnoses) by Ada and Symptoma in 14% (59/437; 27%, 117/437) and 4% (16/437; 13%, 55/437) of patients, respectively. An identical or plausible diagnosis was ranked first (or within the top 5 diagnoses) by Ada and Symptoma in 58% (253/437; 75%, 329/437) and 38% (164/437; 64%, 281/437) of patients, respectively. Ada and Symptoma did not suggest potentially life-threatening diagnoses in 13% (56/437) and 14% (61/437) of patients, respectively. Ada correctly triaged, undertriaged, and overtriaged 34% (149/437), 13% (58/437), and 53% (230/437) of patients, respectively. A total of 88% (385/437) and 78% (342/437) of participants rated Ada and Symptoma as very easy or easy to use, respectively. Ada's NPS was -34 (55% [239/437] detractors; 21% [93/437] promoters) and Symptoma's NPS was -47 (63% [275/437] detractors and 16% [70/437]) promoters., Conclusions: Ada demonstrated a higher diagnostic accuracy than Symptoma, and substantially more patients would recommend Ada and assessed Ada as easy to use. The high number of unrecognized potentially life-threatening diagnoses by both SCs and inappropriate triage advice by Ada was alarming. Overall, the trustworthiness of SC recommendations appears questionable. SC authorization should necessitate rigorous clinical evaluation studies to prevent misdiagnoses, fatal triage advice, and misuse of scarce medical resources., Trial Registration: German Register of Clinical Trials DRKS00024830; https://drks.de/search/en/trial/DRKS00024830., (©Johannes Knitza, Ragip Hasanaj, Jonathan Beyer, Franziska Ganzer, Anna Slagman, Myrto Bolanaki, Hendrik Napierala, Malte L Schmieding, Nizam Al-Zaher, Till Orlemann, Felix Muehlensiepen, Julia Greenfield, Nicolas Vuillerme, Sebastian Kuhn, Georg Schett, Stephan Achenbach, Katharina Dechant. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 20.08.2024.)

Background: Evidence on the health benefits of spending time in nature has highlighted the importance of provision of blue and green spaces where people live. The potential for health benefits offered by nature exposure, however, extends beyond health promotion to health treatment. Social prescribing links people with health or social care needs to community-based, non-clinical health and social care interventions to improve health and wellbeing. Nature-based social prescribing (NBSP) is a variant that uses the health-promoting benefits of activities carried out in natural environments, such as gardening and walking. Much current NBSP practice has been developed in the UK, and there is increasing global interest in its implementation. This requires interventions to be adapted for different contexts, considering the needs of populations and the structure of healthcare systems., Methods: This paper presents results from an expert group participatory workshop involving 29 practitioners, researchers, and policymakers from the UK and Germany's health and environmental sectors. Using the UK and Germany, two countries with different healthcare systems and in different developmental stages of NBSP practice, as case studies, we analysed opportunities, challenges, and facilitators for the development and implementation of NBSP., Results: We identified five overarching themes for developing, implementing, and evaluating NBSP: Capacity Building; Accessibility and Acceptability; Networks and Collaborations; Standardised Implementation and Evaluation; and Sustainability. We also discuss key strengths, weaknesses, opportunities, and threats for each overarching theme to understand how they could be developed to support NBSP implementation., Conclusions: NBSP could offer significant public health benefits using available blue and green spaces. We offer guidance on how NBSP implementation, from wider policy support to the design and evaluation of individual programmes, could be adapted to different contexts. This research could help inform the development and evaluation of NBSP programmes to support planetary health from local and global scales., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [JA – member of the Steering Group of the Scottish Social Prescribing Network; associate member of the One Health Breakthrough Partnership; and member of the Pharma Pollution Hub. ML – director of Social Prescribing Evidence Hub in Ireland and author of the first social prescribing book. GI − scientific and therapeutic interest in NBSP, its implementation into the German health system to foster nature-based intervention for prevention and therapy. KK − offers nature-based and sustainable interventions in the field of prevention and therapy at VERDE in Leipzig, Germany. SP – co-founder of One Health Breakthrough Partnership in Scotland, and advisor to the Pharma Pollution Hub in England. JR − active and ongoing interest in NBSP, its implementation, and how NBSP can benefit wetland conservation. KW − Clinical Supervisor for the Active Health Link Worker Project, Velocity Cafe & Bicycle Workshop social enterprise, funded by NHS Highland and Transport Scotland.]., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: This protocol outlines a scoping review with the objective of identifying and exploring planetary health considerations within existing health guidelines and health technology assessments (HTA). The insights gained from this review will serve as a basis for shaping future Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) guidance on planetary health., Methods: We will adhere to the JBI methodology for scoping reviews. We will conduct a comprehensive search and screening of results in all languages across various databases including MEDLINE, EMBASE, CINAHL, Global Health, Health Systems Evidence, Greenfile, and Environmental Issues. Additionally, we will supplement this search with resources such as the GIN library, BIGG database, Epistemonikos, GRADE guidelines repository, GRADEpro Guideline Development Tool Database, MAGICapp, NICE website, WHO websites, and a manual exploration of unpublished relevant documents using Google incognito mode. Two independent reviewers will screen and assess the full texts of identified documents according to the eligibility criteria. The following information from each full text will be extracted: document title; first author's name; publication year; language; document type; document as a guideline or HTA; the topic/discipline; document purpose/study objective; developing/sponsoring organization; the country in which the study/guideline/HTA report was conducted; definition of planetary health or related concept provided; types of planetary health experts engaged; study methods; suggested methods to assess planetary health; use of secondary data on planetary health outcomes; description for use of life cycle assessment; description for assessing the quality of life cycle; population/intended audience; interventions; category; applicable planetary health boundaries; consideration of social justice/global equity; phase of intervention in life cycle related to planetary health addressed; the measure of planetary health impact; impact on biodiversity/land use; one health/animal welfare mention; funding; and conflict of interest. Data analysis will involve a combination of descriptive statistics and directed content analysis, with results presented in a narrative format and displayed in tables and graphs., Discussion: The final review results will be submitted to open-access peer-reviewed journals for publication when they become available. The research findings will also be disseminated at relevant planetary health conferences and workshops., Systematic Review Registration: Open Science Framework ( https://osf.io/3jmsa )., (© 2024. The Author(s).)

Objective: This scoping review aims to provide an overview of how theories were used in the development or evaluation of social prescribing (SP) intervention studies., Background: SP describes a patient pathway where general practitioners (GPs) connect patients with community activities through referrals to link workers. This review seeks to understand the explanations provided for the outcomes and implementation process of SP., Inclusion Criteria: Studies using a defined theory to develop or evaluate a specific SP intervention in primary care and the community sector., Methods: This scoping review was conducted in accordance with JBI methodology. The following databases were searched on 8 th of July 2022: PubMed, ASSIA, Cochrane, Cinahl, PsycINFO, Social Care Online, Sociological Abstracts, Scopus, and Web of Science. The search only considered English language texts. Additional literature was identified by searching relevant web pages and by contacting experts. The selection of sources and the data extraction was done by two reviewers independently., Results: The search resulted in 4240 reports, of which 18 were included in the scoping review. Of these, 16 were conducted in the UK, one in Canada and one in Australia. The majority of reports employed a qualitative approach (11/18). Three were study protocols. 11 distinct theories were applied to explain outcomes (4 theories), differences in outcomes (3 theories), and the implementation of the intervention (4 theories). In terms of practical application, the identified theories were predominantly used to explain and understand qualitative findings. Only one theory was used to define variables for hypothesis testing. All theories were used for the evaluation and none for the development of SP., Conclusion: The theories influenced which outcomes the evaluation assessed, which causal pathway was expected to generate these outcomes, and which methodological approaches were used. All three groups of theories that were identified focus on relevant aspects of SP: fostering positive patient/community outcomes, addressing inequalities by considering the context of someone's individual circumstances, and successfully implementing SP by collaboratively working across professions and institutional boundaries. Additional insight is required regarding the optimal use of theories in practical applications., (© 2024. The Author(s).)

Background: Breast cancer and cervical cancer are among the most common cancers in women in Germany. Early detection examinations such as mammography and the cervical smear test (Pap-test) have been shown to contribute to the reduction in the mortality and/or incidence of these cancers and can be utilised free of charge by women in certain age groups as part of national screening programmes. Analyses show that the use of health services varies regionally, especially when comparing the federal states of the former German Democratic Republic (GDR, Eastern Germany) and the Federal Republic of Germany (FRG, Western Germany). This study investigated to what extent the utilisation of mammography examinations and Pap-tests by women differs in federal states of former GDR and FRG., Methods: For this purpose, we analysed data from the nationwide health survey GEDA14/15 conducted by the Robert Koch Institute (RKI) in 2014 and 2015. We calculated weighted proportions and compared attendance between eastern and western German states by a Chi-Square-test. Additionally, we conducted regression analysis to adjust for socio-economic status, living environment and place of birth., Results: 2,772 female participants aged 20-34 years were analysed for Pap-test attendance in the last two years and 4,323 female participants aged 50-69 years old were analysed for mammography screening attendance in the last two years. 50-69-year-old women in eastern German states were with 78.3% (95%-CI 75.3%, 81.2%) more likely to attend mammography screening than in western Germany with 73.4% (95%-CI 71.8%, 74.9%). Pap-test uptake was statistically significantly higher in the East of Germany with 83.3% (95%-CI 79.6%, 87.1%) compared to 77.5% (95%-CI 75.8%, 79.3%) in the West of Germany. This relationship was robust to adjusting for socio-economic status, living environment and place of birth., Conclusions: Cultural influences and socialization in the GDR might explain the higher utilisation of these cancer screening examinations at least to some extent. This could have many reasons, for example a higher health awareness through education or a possible greater trust in medical structures and the associated higher compliance of women. These hypotheses should be further explored to increase the uptake of screening examinations by women in Germany., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Previous studies have revealed that users of symptom checkers (SCs, apps that support self-diagnosis and self-triage) are predominantly female, are younger than average, and have higher levels of formal education. Little data are available for Germany, and no study has so far compared usage patterns with people's awareness of SCs and the perception of usefulness., Objective: We explored the sociodemographic and individual characteristics that are associated with the awareness, usage, and perceived usefulness of SCs in the German population., Methods: We conducted a cross-sectional online survey among 1084 German residents in July 2022 regarding personal characteristics and people's awareness and usage of SCs. Using random sampling from a commercial panel, we collected participant responses stratified by gender, state of residence, income, and age to reflect the German population. We analyzed the collected data exploratively., Results: Of all respondents, 16.3% (177/1084) were aware of SCs and 6.5% (71/1084) had used them before. Those aware of SCs were younger (mean 38.8, SD 14.6 years, vs mean 48.3, SD 15.7 years), were more often female (107/177, 60.5%, vs 453/907, 49.9%), and had higher formal education levels (eg, 72/177, 40.7%, vs 238/907, 26.2%, with a university/college degree) than those unaware. The same observation applied to users compared to nonusers. It disappeared, however, when comparing users to nonusers who were aware of SCs. Among users, 40.8% (29/71) considered these tools useful. Those considering them useful reported higher self-efficacy (mean 4.21, SD 0.66, vs mean 3.63, SD 0.81, on a scale of 1-5) and a higher net household income (mean EUR 2591.63, SD EUR 1103.96 [mean US $2798.96, SD US $1192.28], vs mean EUR 1626.60, SD EUR 649.05 [mean US $1756.73, SD US $700.97]) than those who considered them not useful. More women considered SCs unhelpful (13/44, 29.5%) compared to men (4/26, 15.4%)., Conclusions: Concurring with studies from other countries, our findings show associations between sociodemographic characteristics and SC usage in a German sample: users were on average younger, of higher socioeconomic status, and more commonly female compared to nonusers. However, usage cannot be explained by sociodemographic differences alone. It rather seems that sociodemographics explain who is or is not aware of the technology, but those who are aware of SCs are equally likely to use them, independently of sociodemographic differences. Although in some groups (eg, people with anxiety disorder), more participants reported to know and use SCs, they tended to perceive them as less useful. In other groups (eg, male participants), fewer respondents were aware of SCs, but those who used them perceived them to be more useful. Thus, SCs should be designed to fit specific user needs, and strategies should be developed to help reach individuals who could benefit but are not aware of SCs yet., (©Marvin Kopka, Lennart Scatturin, Hendrik Napierala, Daniel Fürstenau, Markus A Feufel, Felix Balzer, Malte L Schmieding. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 20.06.2023.)

Background: While reporting of individual conflicts of interest is formalised, it is unclear to what extent the funding of clinical practice guidelines (CPGs) is formally reported. The aim of this study is to explore the accuracy and comprehensiveness of reporting on funding in German CPGs., Methods: We searched for CPGs in the registry of the Association of the Scientific Medical Societies in Germany in July 2020. Information on guideline funding was categorised by two reviewers independently and discrepancies were clarified by discussion with a third reviewer. Accuracy and comprehensiveness of reporting on funding was assessed using the German Instrument for Methodological Guideline Appraisal (DELBI)., Results: We included 507 CPGs published between 2015 and 2020 in the main analysis. 23/507 (4.5%) of the CPGs achieved the highest DELBI score by including information on funding sources, expenses and the amount of funding provided, as well as a statement on the independence of the guideline authors from the funding institution(s). CPGs with more rigorous methodological requirements (systematic review of the literature and/or structured consensus-building) received higher DELBI scores., Conclusion: German CPGs do not communicate their funding transparently. Transparency of CPG funding could be achieved by making it mandatory to publish information for all guidelines. For that purpose, a standardised form and guidance should be developed., (© 2023. The Author(s).)

Background: Due to the increasing use of online health information, symptom checkers have been developed to provide an individualized assessment of health complaints and provide potential diagnoses and an urgency estimation. It is assumed that they support patient empowerment and have a positive impact on patient-physician interaction and satisfaction with care. Particularly in the emergency department (ED), symptom checkers could be integrated to bridge waiting times in the ED, and patients as well as physicians could take advantage of potential positive effects. Our study therefore aims to assess the impact of symptom assessment application (SAA) usage compared to no SAA usage on the patient-physician interaction in self-referred walk-in patients in the ED population., Methods: In this multi-center, 1:1 randomized, controlled, parallel-group superiority trial, 440 self-referred adult walk-in patients with a non-urgent triage category will be recruited in three EDs in Berlin. Eligible participants in the intervention group will use a SAA directly after initial triage. The control group receives standard care without using a SAA. The primary endpoint is patients' satisfaction with the patient-physician interaction assessed by the Patient Satisfaction Questionnaire., Discussion: The results of this trial could influence the implementation of SAA into acute care to improve the satisfaction with the patient-physician interaction., Trial Registration: German Clinical Trials Registry DRKS00028598 . Registered on 25.03.2022., (© 2022. The Author(s).)

Introduction: Social prescribing (SP) aims to provide targeted psychosocial support and close the gap between medical and non-medical services. This review assesses the effectiveness of community-based SP interventions., Methods: We performed a systematic review and qualitative synthesis of interventional studies of community referral interventions focused on facilitating psychosocial support. We considered health-related endpoints, other patient reported outcomes, or health care utilization. Six databases, grey literature, and additional trials registers were searched. Results were screened in a two-step process, followed by data extraction, each by two independent reviewers. If data permitted such, effect sizes were calculated. Risk of bias was assessed with the EPHPP and the Cochrane RoB2 tools., Results: We identified 68 reports from 53 different projects, three were controlled studies. Uncontrolled studies with shorter time frames frequently reported positive effects. This could largely not be seen in controlled settings and for longer follow-up periods. Designs, populations, and outcomes evaluated were heterogeneous with high risk of bias for most studies., Discussion and Conclusion: Current evidence suggests positive effects of SP on a variety of relevant endpoints. Due to quality deficits in the available studies, scope for conclusions concerning clinical relevance and sustainability is limited. Further methodologically rigorous controlled trials are needed., Competing Interests: The authors declare no competing interests., (Copyright: © 2022 The Author(s).)

Background: Many patients suffering from peripheral arterial disease (PAD) are dependent on bypass surgery. However, in some patients no suitable replacements (i.e. autologous or prosthetic bypass grafts) are available. Advances have been made to develop autologous tissue engineered vascular grafts (TEVG) using endothelial colony forming cells (ECFC) obtained by peripheral blood draw in large animal trials. Clinical translation of this technique, however, still requires additional data for usability of isolated ECFC from high cardiovascular risk patients. Bovine carotid arteries (BCA) were decellularized using a combined SDS (sodium dodecyl sulfate) -free mechanical-osmotic-enzymatic-detergent approach to show the feasibility of xenogenous vessel decellularization. Decellularized BCA chips were seeded with human ECFC, isolated from a high cardiovascular risk patient group, suffering from diabetes, hypertension and/or chronic renal failure. ECFC were cultured alone or in coculture with rat or human mesenchymal stromal cells (rMSC/hMSC). Decellularized BCA chips were evaluated for biochemical, histological and mechanical properties. Successful isolation of ECFC and recellularization capabilities were analyzed by histology., Results: Decellularized BCA showed retained extracellular matrix (ECM) composition and mechanical properties upon cell removal. Isolation of ECFC from the intended target group was successfully performed (80% isolation efficiency). Isolated cells showed a typical ECFC-phenotype. Upon recellularization, co-seeding of patient-isolated ECFC with rMSC/hMSC and further incubation was successful for 14 (n = 9) and 23 (n = 5) days. Reendothelialization (rMSC) and partial reendothelialization (hMSC) was achieved. Seeded cells were CD31 and vWF positive, however, human cells were detectable for up to 14 days in xenogenic cell-culture only. Seeding of ECFC without rMSC was not successful., Conclusion: Using our refined decellularization process we generated easily obtainable TEVG with retained ECM- and mechanical quality, serving as a platform to develop small-diameter (< 6 mm) TEVG. ECFC isolation from the cardiovascular risk target group is possible and sufficient. Survival of diabetic ECFC appears to be highly dependent on perivascular support by rMSC/hMSC under static conditions. ECFC survival was limited to 14 days post seeding.

Islet-based recellularization of decellularized, repurposed rat livers may form a transplantable Neo-Pancreas. The aim of this study is the establishment of the necessary protocols, the evaluation of the organ structure and the analysis of the islet functionality ex vivo. After perfusion-based decellularization of rat livers, matrices were repopulated with endothelial cells and mesenchymal stromal cells, incubated for 8 days in a perfusion chamber, and finally repopulated on day 9 with intact rodent islets. Integrity and quality of re-endothelialization was assessed by histology and FITC-dextran perfusion assay. Functionality of the islets of Langerhans was determined on day 10 and day 12 via glucose stimulated insulin secretion. Blood gas analysis variables confirmed the stability of the perfusion cultivation. Histological staining showed that cells formed a monolayer inside the intact vascular structure. These findings were confirmed by electron microscopy. Islets infused via the bile duct could histologically be found in the parenchymal space. Adequate insulin secretion after glucose stimulation after 1-day and 3-day cultivation verified islet viability and functionality after the repopulation process. We provide the first proof-of-concept for the functionality of islets of Langerhans engrafted in a decellularized rat liver. Furthermore, a re-endothelialization step was implemented to provide implantability. This technique can serve as a bioengineered platform to generate implantable and functional endocrine Neo-Pancreases., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2020. Published by Elsevier Ltd.)

Grey wolves (Canis lupus) are one of the few large terrestrial carnivores that have maintained a wide geographical distribution across the Northern Hemisphere throughout the Pleistocene and Holocene. Recent genetic studies have suggested that, despite this continuous presence, major demographic changes occurred in wolf populations between the Late Pleistocene and early Holocene, and that extant wolves trace their ancestry to a single Late Pleistocene population. Both the geographical origin of this ancestral population and how it became widespread remain unknown. Here, we used a spatially and temporally explicit modelling framework to analyse a data set of 90 modern and 45 ancient mitochondrial wolf genomes from across the Northern Hemisphere, spanning the last 50,000 years. Our results suggest that contemporary wolf populations trace their ancestry to an expansion from Beringia at the end of the Last Glacial Maximum, and that this process was most likely driven by Late Pleistocene ecological fluctuations that occurred across the Northern Hemisphere. This study provides direct ancient genetic evidence that long-range migration has played an important role in the population history of a large carnivore, and provides insight into how wolves survived the wave of megafaunal extinctions at the end of the last glaciation. Moreover, because Late Pleistocene grey wolves were the likely source from which all modern dogs trace their origins, the demographic history described in this study has fundamental implications for understanding the geographical origin of the dog., (© 2019 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.)

Background: The reliability of clinical practice guidelines has been disputed because guideline panel members are often burdened with financial conflicts of interest (COI). Current recommendations for COI regulation advise not only detailed declaration but also active management of conflicts. To continuously assess COI declaration and management in German guidelines we established the public database LeitlinienWatch (GuidelineWatch)., Methods: We analyzed all German guidelines at the highest methodological level (S3) that included recommendations for pharmacological therapy (n = 67) according to five criteria: declaration and assessment of COI, composition of the guideline development group, independence of the coordinators and lead authors, imposed abstentions because of COI and public external review. Each criterion was assessed using predefined outcome categories., Results: Most guidelines (76%) contained a detailed declaration of COI. However, none of the guidelines provided full transparency of COI assessment results. The guideline group was composed of a majority of participants with COI in 55% of the guidelines, no guideline was free of participants with COI. Only 9% of guidelines had coordinators and lead authors without any financial COI. Most guidelines (70%) did not provide a rule for abstentions for participants with COI. In 21% of guidelines there was a rule, but abstentions were either not practiced or not documented, whereas in 7% partial abstentions and in 2% complete abstentions were documented. Two thirds of the guideline drafts (67%) were not externally reviewed via a public website., Conclusions: COI are usually documented in detail in German guidelines of the highest methodological level. However, considerable improvement is needed regarding active management of COI, including recruitment of independent experts for guideline projects, abstention from voting for participants with COI and external review of the guideline draft. We assume that the publicly available ratings on GuidelineWatch will improve the handling of conflicts of interest in guideline development.

Decellularization of livers is a well-established procedure. Data on different reseeding techniques or the functional evolution and reorganization processes of repopulated grafts remains limited. A proprietary, customized bioreactor was established to repopulate decellularized rat livers (n = 21) with primary rat hepatocytes (150 × 10 6 cells) via the hepatic artery and to subsequently evaluate graft morphology and function during 7 days of ex vivo perfusion. Grafts were analysed at 1 h, 6 h, 12 h, 24 h, 3 days, 5 days and 7 days after recellularization (all n = 3) by immunohistological evaluation, hepatocyte-related enzyme (aspartate transaminase, alanine transaminase and lactate dehydrogenase) and albumin measurement in the perfusate. This appears to be the first available protocol for repopulation of rat livers via the hepatic artery. Within the first 24 h after repopulation, the hepatocytes seemed to migrate out of the vascular network and form clusters in the parenchymal space around the vessels. Graft function increased for the first 24 h after repopulation with a significantly higher function compared to standard two-dimensional culture after 24 h. Thereafter, graft function constantly decreased with significantly lower values after 6 days and 7 days of perfusion, although histologically viable hepatocytes were found even after this period. The data suggests that, owing to a constant loss of function, repopulated grafts should potentially be implanted as soon as cell engraftment and graft re-organization are completed. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background: Extrahepatic bile duct injuries remain severe complications during cholecystectomies and often require reconstruction by bilioenteric anastomosis (i.e., hepaticojejunostomy), which comes with further long-term complications (e.g., recurring ascending cholangitis, secondary biliary cirrhosis). In the case of inherent extrahepatic biliary atresia or during liver transplant, artificial or engineered bile ducts could allow novel surgical strategies without the need for hepaticojejunostomy., Methods: We present data on the implantation of in vitro-generated neo-bile ducts in 5 domestic pigs. The neo-bile ducts were engineered through decellularization of allogeneic blood vessels and recellularization with autologous cholangiocytes. On postoperative days 0, 1, 7, and 14, blood samples were taken and analyzed (aspartate aminotransferase, alanine aminotransferase, bilirubin, alkaline phosphatase, creatinine, and leukocytes). Magnetic resonance cholangiopancreatography was performed on postoperative day 14 on 1 pig. Fourteen days after implantation, the pigs were sacrificed and the bile ducts were explanted., Results: All pigs survived the complete study period without severe complications. None of the pigs showed signs of biliary leakage or peritonitis. The neo-bile ducts were infiltrated by neutrophils, and neoangiogenesis was observed around and into the implanted tissue., Conclusion: We present a novel strategy for extrahepatic bile duct replacement by implantation of an autologous neo-bile duct generated ex vivo. Whether the presented technique allows the long-term replacement of native bile ducts must be further evaluated., (© 2015 S. Karger AG, Basel.)

Primary human hepatocytes are widely used for basic research, pharmaceutical testing, and therapeutic concepts in regenerative medicine. Human hepatocytes can be isolated from resected liver tissue. Preoperative portal vein embolization (PVE) is increasingly used to decrease the risk of delayed postoperative liver regeneration by induction of selective hypertrophy of the future remnant liver tissue. The aim of this study was to investigate the effect of PVE on the outcome of hepatocyte isolation. Primary human hepatocytes were isolated from liver tissue obtained from partial hepatectomies (n = 190) using the two-step collagenase perfusion technique followed by Percoll purification. Of these hepatectomies, 27 isolations (14.2%) were performed using liver tissue obtained from patients undergoing PVE before surgery. All isolations were characterized using parameters that had been described in the literature as relevant for the outcome of hepatocyte isolation. The isolation outcomes of the PVE and the non-PVE groups were then compared before and after Percoll purification. Metabolic parameters (transaminases, urea, albumin, and vascular endothelial growth factor secretion) were measured in the supernatant of cultured hepatocytes for more than 6 days (PVE: n = 4 and non-PVE: n = 3). The PVE and non-PVE groups were similar in regard to donor parameters (sex, age, and indication for surgery), isolation parameters (liver weight and cold ischemia time), and the quality of the liver tissue. The mean initial viable cell yield did not differ between the PVE and non-PVE groups (10.16 ± 2.03 × 10(6) cells/g vs. 9.70 ± 0.73 × 10(6) cells/g, p = 0.499). The initial viability was slightly better in the PVE group (77.8% ± 2.03% vs. 74.4% ± 1.06%). The mean viable cell yield (p = 0.819) and the mean viability (p = 0.141) after Percoll purification did not differ between the groups. PVE had no effect on enzyme leakage and metabolic activity of cultured hepatocytes. Although PVE leads to drastic metabolic alterations and changes in hepatic blood flow, embolized liver tissue is a suitable source for the isolation of primary human hepatocytes and is equivalent to untreated liver tissue in regard to cell yield and viability.

Decellularization and recellularization of parenchymal organs may enable the generation of functional organs in vitro, and several protocols for rodent liver decellularization have already been published. We aimed to improve the decellularization process by construction of a proprietary perfusion device enabling selective perfusion via the portal vein and/or the hepatic artery. Furthermore, we sought to perform perfusion under oscillating surrounding pressure conditions to improve the homogeneity of decellularization. The homogeneity of perfusion decellularization has been an underestimated factor to date. During decellularization, areas within the organ that are poorly perfused may still contain cells, whereas the extracellular matrix (ECM) in well-perfused areas may already be affected by alkaline detergents. Oscillating pressure changes can mimic the intraabdominal pressure changes that occur during respiration to optimize microperfusion inside the liver. In the study presented here, decellularized rat liver matrices were analyzed by histological staining, DNA content analysis and corrosion casting. Perfusion via the hepatic artery showed more homogenous results than portal venous perfusion did. The application of oscillating pressure conditions improved the effectiveness of perfusion decellularization. Livers perfused via the hepatic artery and under oscillating pressure conditions showed the best results. The presented techniques for liver harvesting, cannulation and perfusion using our proprietary device enable sophisticated perfusion set-ups to improve decellularization and recellularization experiments in rat livers.