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This study investigated the effect of low-dose aspirin in primary adult liver transplantation (LT) on acute cellular rejection (ACR) as well as arterial patency rates. The use of low-dose aspirin after LT is practiced by many transplant centers to minimize the risk of hepatic artery thrombosis (HAT), although solid recommendations do not exist. However, aspirin also possesses potent anti-inflammatory properties and might mitigate inflammatory processes after LT, such as rejection. Therefore, we hypothesized that the use of aspirin after LT has a protective effect against ACR. This is an international, multicenter cohort study of primary adult deceased donor LT. The study included 17 high-volume LT centers and covered the 3-year period from 2013 to 2015 to allow a minimum 5-year follow-up. In this cohort of 2365 patients, prophylactic antiplatelet therapy with low-dose aspirin was administered in 1436 recipients (61%). The 1-year rejection-free survival rate was 89% in the aspirin group versus 82% in the no-aspirin group (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.63-0.94; p = 0.01). The 1-year primary arterial patency rates were 99% in the aspirin group and 96% in the no-aspirin group with an HR of 0.23 (95% CI, 0.13-0.40; p

Plagiarism and other transgressions of the norms of academic integrity appear to be a persistent problem among upper secondary students. Numerous surveys have revealed high levels of infringement of what appear to be clearly stated rules. Less attention has been given to students' understanding of academic integrity, and to the potential misconceptions and false beliefs that may make it difficult for them to comply with existing rules and handle complex real-life situations. In this paper we report findings from a survey of European upper secondary students' views on issues relating to academic integrity. We relate these findings to the students' training about academic integrity, self-reported level of questionable behavior and country of study. A total of 1654 students at 51 institutions located in 6 European countries participated in the study. The participants generally believed they had a good understanding of the rules applying to them and knew how to behave in compliance with norms of academic integrity. The results indicate, however, that often, in practice, this belief was mistaken. Many students had an inadequate understanding of core elements of academic integrity. They were uncertain about how to act, and they struggled in the handling of complex situations that require context-sensitive judgment. While some differences between countries were identified, they were modest and exhibited no clear pattern. Our results also suggest that reducing students' level of uncertainty and, to a lesser degree, improving their level of knowledge could lead them to engage less in certain types of questionable behaviours. Surprisingly, the effect of academic training is modest and ambiguous. The study also confirms that perception of peer behaviour has the strongest association with student engagement in questionable behaviours. Thus, academic integrity at the upper secondary level cannot be explained simply in terms of individual ethics or knowledge.

Objective: The aim was to analyze the learning curves of minimal invasive liver surgery (MILS) and propose standardized reporting. Background: MILS offers benefits compared with open resections. For a safe introduction along the learning curve, formal training is recommended. However, definitions of learning curves and methods to assess it lack standardization. Methods: A systematic review of PubMed, Web of Science, and CENTRAL databases identified studies on learning curves in MILS. The primary outcome was the number needed to overcome the learning curve. Secondary outcomes included endpoints defining learning curves and characterization of different learning phases (competency, proficiency, and mastery). Results: Sixty articles with 12,241 patients and 102 learning curve analyses were included. The laparoscopic and robotic approach was evaluated in 71 and 18 analyses and both approaches combined in 13 analyses. Sixty-one analyses (60%) based the learning curve on statistical calculations. The most often used parameters to define learning curves were operative time (n=64), blood loss (n=54), conversion (n=42), and postoperative complications (n=38). Overall competency, proficiency, and mastery were reached after 34 [interquartile range (IQR) 19–56], 50 (IQR 24–74), and 58 (IQR 24–100) procedures, respectively. Intraoperative parameters improved earlier (operative time: competency to proficiency to mastery: −13%, 2%; blood loss: competency to proficiency to mastery: –33%, 0%; conversion rate (competency to proficiency to mastery; −21%, −29%), whereas postoperative complications improved later (competency to proficiency to mastery: −25%, −41%). Conclusions: This review summarizes the highest evidence on learning curves in MILS taking into account different definitions and confounding factors. A standardized 3-phase reporting of learning phases (competency, proficiency, and mastery) is proposed and should be followed. [ABSTRACT FROM AUTHOR]

Objective: To establish the first consensus guidelines on the safety and indications of robotics in Hepato-Pancreatic-Biliary (HPB) surgery. The secondary aim was to identify priorities for future research. Background: HPB robotic surgery is reaching the IDEAL 2b exploration phase for innovative technology. An objective assessment endorsed by the HPB community is timely and needed. Methods: The ROBOT4HPB conference developed consensus guidelines using the Zurich-Danish model. An impartial and multidisciplinary jury produced unbiased guidelines based on the work of 10 expert panels answering predefined key questions and considering the best-quality evidence retrieved after a systematic review. The recommendations conformed with the GRADE and SIGN50 methodologies. Results: Sixty-four experts from 20 countries considered 285 studies, and the conference included an audience of 220 attendees. The jury (n=10) produced recommendations or statements covering 5 sections of robotic HPB surgery: technology, training and expertise, outcome assessment, and liver and pancreatic procedures. The recommendations supported the feasibility of robotics for most HPB procedures and its potential value in extending minimally invasive indications, emphasizing, however, the importance of expertise to ensure safety. The concept of expertise was defined broadly, encompassing requirements for credentialing HPB robotics at a given center. The jury prioritized relevant questions for future trials and emphasized the need for prospective registries, including validated outcome metrics for the forthcoming assessment of HPB robotics. Conclusions: The ROBOT4HPB consensus represents a collaborative and multidisciplinary initiative, defining state-of-the-art expertise in HPB robotics procedures. It produced the first guidelines to encourage their safe use and promotion. [ABSTRACT FROM AUTHOR]

Primary liver carcinomas with both hepatocytic and cholangiocytic differentiation have been referred to as "combined (or mixed) hepatocellular-cholangiocarcinoma." These tumors, although described over 100 years ago, have attracted greater attention recently because of interest in possible stem cell origin and perhaps because of greater frequency and clinical recognition. Currently, because of a lack of common terminology in the literature, effective treatment and predictable outcome data have been challenging to accrue. This article represents a consensus document from an international community of pathologists, radiologists, and clinicians who have studied and reported on these tumors and recommends a working terminology for diagnostic and research approaches for further study and evaluation.ConclusionIt is recommended that diagnosis is based on routine histopathology with hematoxylin and eosin (H&E); immunostains are supportive, but not essential for diagnosis. (Hepatology 2018;68:113-126).

Objective: To assess the impact of normothermic machine perfusion (NMP) on patients, medical teams, and costs by gathering global insights and exploring current limitations. Background: NMP for ex situ liver graft perfusion is gaining increasing attention for its capability to extend graft preservation. It has the potential to transform liver transplantation (LT) from an urgent to a purely elective procedure, which could revolutionize LT logistics, reduce burden on patients and health care providers, and decrease costs. Methods: A 31-item survey was sent to international transplant directors to gather their NMP experiences and vision. In addition, we performed a systematic review on cost-analysis in LT and assessed studies on cost-benefit in converting urgentto- elective procedures. We compared the costs of available NMPs and conducted a sensitivity analysis of NMP's cost benefits. Results: Of 120 transplant programs contacted, 64 (53%) responded, spanning North America (31%), Europe (42%), Asia (22%), and South America (5%). Of the total, 60% had adopted NMP, with larger centers ( > 100 transplants/year) in North America and Europe more likely to use it. The main NMP systems were OrganOx-metra (39%), XVIVO (36%), and Trans- Medics-OCS (15%). Despite NMP adoption, 41% of centers still perform > 50% of LTs at nights/weekends. Centers recognized NMP's benefits, including improved work satisfaction and patient outcomes, but faced challenges like high costs and machine complexity. 16% would invest $100,000 to 500'000, 33% would invest $50,000 to 100'000, 38% would invest $10,000 to 50'000, and 14% would invest < $10,000 in NMP. These results were strengthened by a cost analysis for NMP in emergency-to-elective LT transition. Accordingly, while liver perfusions with disposables up to $10,000 resulted in overall positive net balances, this effect was lost when disposables' cost amounted to > $40,000/ organ. Conclusions: The adoption of NMP is hindered by high costs and operational complexity. Making LT elective through NMP could reduce costs and improve outcomes, but overcoming barriers requires national reimbursements and simplified, automated NMP systems for multiday preservation. [ABSTRACT FROM AUTHOR]

Objective: To provide improved guidance for the consistent application of the Clavien-Dindo classification (CDC) and Comprehensive Complication Index (CCI®) in challenging clinical scenarios. Background: Standardized outcome reporting is key for the proper assessment of surgical procedures. A recent consensus conference recommended the CDC and the CCI® for assessing postoperative morbidity. Several challenging scenarios for grading complications still require evidence-based guidance, and the use of the 2 metrics in randomized controlled trials (RCTs) remains unexplored. Methods: We assessed the use of the CDC and CCI® as an outcome measure in a systematic literature search. In addition, we asked 163 international surgeons to critically evaluate and independently grade complications in 20 complex clinical scenarios. Finally, a Core Group of 5 experts used this information to develop consistent recommendations. Results: Until July 2023, 1327 RCTs selected the CDC and/or CCI® to assess morbidity. Annual use was steadily increasing with now over 200 new RCTs per year. However, only a third (n = 335) of published RCTs provided the complete range of CDC grades, including all subgrades. Eighty-nine out of 163 surgeons (response rate: 55%) completed the questionnaire that served as a basis for the recommendations: repetitive interventions that are required to treat one complication, complications followed by further complications, complications occurring before referral, and expected and unrelated complications to the original procedure should all be counted separately and included in the CCI®. Invasive blank diagnostic interventions should not be considered a complication. Conclusions: The increasing use of the CDC and CCI® in RCTs highlights the importance of their standardized application. The current consensus on various difficult scenarios may offer novel guidance for the consistent use of the CDC and CCI®, aiming to improve complication reporting and better quality control, ultimately benefiting all health care stakeholders and, first and foremost, all patients. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the impact of robotic techniques on organ transplantation outcomes. Background: The evolution of organ transplantation is becoming influenced by the adoption of minimally invasive techniques, transitioning from laparoscopic to robotic methods. Robotic surgery has emerged as a significant advancement, providing superior precision and outcomes compared with traditional approaches. Methods: This perspective includes a systematic review of the literature, original data from a high-volume center, as well as an international survey focusing on perceptions related to robotic versus laparoscopic and open approaches. Results: The systematic review and meta-analysis revealed lower morbidity with robotic donor nephrectomy, recipient kidney transplant and donor hepatectomy. Our center's experience, with over 3000 minimally invasive transplant procedures (kidney, liver, donor, and recipient), supports the superiority of robotic transplant surgery (RTS). The global survey confirms this shift, revealing a preference for robotic approaches due to their reduced morbidity, despite challenges such as access to the robotic system and cost. Conclusions: This comprehensive overview including a systematic review, original data, and perceptions derived from the international survey demonstrate the superiority of robotic transplant surgery (RTS) across a range of organ transplantations, for both donors and recipients. The future of RTS depends on the efforts of the surgical community in addressing challenges such as economic implications, the need for specialized surgical training for numerous surgeons, as well as wide access to robotic systems worldwide. [ABSTRACT FROM AUTHOR]

Objective: To define the concept of surgeon-scientists and identify the root causes of their decline in number and impact. The secondary aim was to provide actionable remedies. Background: Surgeons who conduct research in addition to patient care are referred to as "surgeon-scientists." While their value to society remains undisputed, their numbers and associated impact have been plunging. While reasons have been well identified along with proposals for countermeasures, their application has largely failed. Methods: We conducted a systematic review covering all aspects of surgeon-scientists together with a global online survey among 141 young academic surgeons. Using gap analysis, we determined implementation gaps for proposed measures. Then, we developed a comprehensive rescue package. Results: A surgeon-scientist must actively and continuously engage in both patient care and research. Competence in either field must be established through protected training and criteria of excellence, particularly reflecting contribution to innovation. The decline of surgeon-scientists has reached an unprecedented magnitude. Leadership turning hospitals into "profit factories" is one reason, a flawed selection process not exclusively based on excellence is another. Most importantly, the appreciation for the academic mission has vanished. Along with fundamentally addressing these root causes, surgeon-scientists' path to excellence must be streamlined, and their continuous devotion to innovation cherished. Conclusions: The journey of the surgeon-scientist is at a crossroads. As a society, we either adapt and shift our priorities again towards innovation or capitulate to greed for profit, permanently losing these invaluable professionals. Successful rescue packages must not only involve hospitals and universities but also the political sphere. [ABSTRACT FROM AUTHOR]

The Clavien-Madadi classification is a novel instrument for the assessment and grading of unexpected events in pediatric surgery, based on the Clavien-Dindo classification. The system has been adjusted to better fit the pediatric population in a prospective single-center study. There is a need now to validate the Clavien-Madadi classification within an international expert network. A pediatric surgical working group created 19 case scenarios with unexpected events in a multi-staged process. Those were circulated within the European Reference Network of Inherited and Congenital Anomalies (ERNICA) and surgeons were instructed to rate the scenarios according to the Clavien-Madadi vs. Clavien-Dindo classification. 59 surgeons from 12 European countries completed the questionnaire. Based on ratings of the case scenarios, the Clavien-Madadi classification showed significantly superior agreement rates of the respondents (85.9% vs 76.2%; p < 0.05) and was less frequently considered inaccurate for rating the pediatric population compared to Clavien-Dindo (2.1% vs 11.1%; p = 0.05). Fleiss' kappa analysis showed slightly higher strength of agreement using the Clavien-Madadi classification (0.74 vs 0.69). Additionally, intraclass correlation coefficient was slightly higher for the Clavien-Madadi compared to the Clavien-Dindo classification (ICC just 0.93 vs 0.89; ICC unjust 0.93 vs 0.89). More pediatric surgeons preferred the Clavien-Madadi classification for the case scenarios (43.0% vs 11.8%; p = 0.002) and advantages of the Clavien-Madadi were confirmed by 81.4% of the surgeons. The Clavien-Madadi classification is an accurate and reliable instrument for the grading of unexpected events in pediatric surgery. We therefore recommend its application in clinical and academic pediatric surgical practice. III. [ABSTRACT FROM AUTHOR]

BACKGROUND & AIMS: Organ shortage has led to the use of steatotic livers in transplantation, despite their elevated susceptibility to ischemia/reperfusion injury (IRI). Matrix metalloproteinase-9 (MMP-9), an inducible gelatinase, is emerging as a central mediator of leukocyte traffic into inflamed tissues. However, its role in steatotic hepatic IRI has yet to be demonstrated. METHODS: We examined the function of MMP-9 in mice fed with a high-fat diet (HFD), which developed approximately 50% hepatic steatosis, predominantly macrovesicular, prior to partial hepatic IRI. RESULTS: The inability of MMP-9(-/-) deficient steatotic mice to express MMP-9 significantly protected these mice from liver IRI. Compared to fatty controls, MMP-9(-/-) steatotic livers showed significantly reduced leukocyte infiltration, proinflammatory cytokine expression, and liver necrosis. Loss of MMP-9 activity preserved platelet endothelial cell adhesion molecule-1 (PECAM-1) expression, a modulator of vascular integrity at the endothelial cell-cell junctions in steatotic livers after IRI. Using in vitro approaches, we show that targeted inhibition of MMP-9 sheltered the extracellular portion of PECAM-1 from proteolytic processing, and disrupted leukocyte migration across this junctional molecule. Moreover, the evaluation of distinct parameters of regeneration, proliferating cell nuclear antigen (PCNA) and histone H3 phosphorylation (pH3), provided evidence that hepatocyte progression into S phase and mitosis was notably enhanced in MMP-9(-/-) steatotic livers after IRI. CONCLUSIONS: MMP-9 activity disrupts vascular integrity at least partially through a PECAM-1 dependent mechanism and interferes with regeneration of steatotic livers after IRI. Our novel findings establish MMP-9 as an important mediator of steatotic liver IRI.

Objectives: To assess the current quality of surgical outcome reporting in the medical literature and to provide recommendations for improvement. Background: In 1996, The Lancet labeled surgery as a "comic opera" mostly referring to the poor quality of outcome reporting in the literature impeding improvement in surgical quality and patient care. Methods: We screened 3 first-tier and 2 second-tier surgical journals, as well as 3 leading medical journals for original articles reporting on results of surgical procedures published over a recent 18-month period. The quality of outcome reporting was assessed using a prespecified 12-item checklist. Results: Six hundred twenty-seven articles reporting surgical outcomes were analyzed, including 125 randomized controlled trials. Only 1 (0.2%) article met all 12 criteria of the checklist, whereas 356 articles (57%) fulfilled less than half of the criteria. The poorest reporting was on cumulative morbidity burden, which was missing in 94% of articles (n= 591) as well as patient-reported outcomes missing in 83% of publications (n=518). Comparing journal groups for the individual criterion, we found moderate to very strong statistical evidence for better quality of reporting in high versus lower impact journals for 7 of 12 criteria and strong statistical evidence for better reporting of patientreported outcomes in medical versus surgical journals (P<0·001). Conclusions: The quality of outcomes reporting in the medical literature remains poor, lacking improvement over the past 20 years onmost key end points. The implementation of standardized outcome reporting is urgently needed to minimize biased interpretation of data thereby enabling improved patient care and the elaboration of meaningful guidelines. [ABSTRACT FROM AUTHOR]

Nudges are soft interventions designed to influence human behaviour. They are increasingly used by policymakers around the world and generate heated controversies over their ethical acceptability. In this article, I depict nudges as science-based technologies, point to new ethical responsibilities they raise--when they are used but also when they are "not" used--and to the necessity of establishing clear evaluation criteria. I then elaborate a four-level framework for evaluating the acceptability of particular nudges. The second part of the article focuses specifically on 'shared preference justifications' (SPJ), that is, arguments of the sort 'nudges help people make better choices as judged by themselves'. I explain why constructing SPJs is important but difficult and propose a framework for doing so. This framework takes autonomy concerns seriously without overstating them and provides a conceptual basis for the development of nudge evaluation procedures easily applicable by decision-makers.