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Markus Krautter,1 Ronja Dittrich,2 Annette Safi,2 Justine Krautter,1 Imad Maatouk,2 Andreas Moeltner,2 Wolfgang Herzog,2 Christoph Nikendei2 1Department of Nephrology, 2Department of General Internal and Psychosomatic Medicine, University of Heidelberg Medical Hospital, Heidelberg, Germany Background: Although Peyton’s four-step approach is a widely used method for skills-lab training in undergraduate medical education and has been shown to be more effective than standard instruction, it is unclear whether its superiority can be attributed to a specific single step. Purpose: We conducted a randomized controlled trial to investigate the differential learning outcomes of the separate steps of Peyton’s four-step approach. Methods: Volunteer medical students were randomly assigned to four different groups. Step-1 group received Peyton’s Step 1, Step-2 group received Peyton’s Steps 1 and 2, Step-3 group received Peyton’s Steps 1, 2, and 3, and Step-3mod group received Peyton’s Steps 1 and 2, followed by a repetition of Step 2. Following the training, the first independent performance of a central venous catheter (CVC) insertion using a manikin was video-recorded and scored by independent video assessors using binary checklists. The day after the training, memory performance during delayed recall was assessed with an incidental free recall test. Results: A total of 97 participants agreed to participate in the trial. There were no statistically significant group differences with regard to age, sex, completed education in a medical profession, completed medical clerkships, preliminary memory tests, or self-efficacy ratings. Regarding checklist ratings, Step-2 group showed a superior first independent performance of CVC placement compared to Step-1 group (P

Markus Krautter,1 Sven Andreesen,2 Nadja Köhl-Hackert,2 Katja Hoffmann,3 Wolfgang Herzog,2 Christoph Nikendei2 1Department of Nephrology, University of Heidelberg, 2Department of General Internal Medicine and Psychosomatics, University of Heidelberg Medical Hospital, 3Department of General Practice and Health Services Research, University Hospital Heidelberg, Heidelberg, Germany Background: Peer-assisted learning (PAL) has become a well-accepted teaching method within medical education. However, descriptions of on-ward PAL programs are rare. A focus group analysis of a newly established PAL program on an internal medicine ward was conducted to provide insights into PAL teaching from a student perspective.Purpose: To provide insights into students' experiences regarding their on-ward training with and without accompanying PAL tutors.Methods: A total of N=168 medical students in their sixth semester participated in the investigation (intervention group: N=88; control group: N=80). The intervention group took part in the PAL program, while the control group received standard on-ward training. There were seven focus groups with N=43 participants (intervention group: four focus groups, N=28 participants; control group: three focus groups, N=15 participants). The discussions were analyzed using content analysis.Results: The intervention group emphasized the role of the tutors as competent and well-trained teachers, most beneficial in supervising clinical skills. Tutors motivate students, help them to integrate into the ward team, and provide a non-fear-based working relationship whereby students' anxiety regarding working on ward decreases. The control group had to rely on autodidactic learning strategies when neither supervising physicians nor final-year students were available.Conclusion: On-ward PAL programs represent a particularly valuable tool for students' support in training clinical competencies on ward. The tutor–student working alliance acts through its flat hierarchy. Nevertheless, tutors cannot represent an adequate substitute for experienced physicians. Keywords: peer-assisted learning, cross-year peer tutoring, undergraduate medical education, final year, internal medicine, clinical skills training

Background: Over multiple years, the didactic concept of „peer-assisted learning“ (PAL) has proved to be valuable for medical education. Particularly in the field of the nowadays widely established Skills-Labs, the assignment of student tutors is both popular and effective. The aim of the underlying study is to assess the current status of PAL programs within German medical faculties’ Skills-Labs regarding their distribution, extent, structure and content based on a nation-wide survey.Methods: All 36 medical faculties in Germany were contacted and asked for their participation (via telephone or in written form) in the survey encompassing 16 central questions as to the structure of established PAL programs. Data obtained were subject to quantitative and qualitative analysis.Results: 35 of 36 (97.2%) medical faculties participated in the survey. A PAL program was shown to be established at 33 (91.7%) faculties. However, the results show distinct differences between different faculties with respect to extent and content of the PAL programs.Conclusions: Among German medical Skills-Labs, PAL has been established almost ubiquitously. Further studies on the conception and standardization of training concepts appear to be pivotal for the advancement of PAL in the context of Skills-Labs.

In the Mesozoic Era siliceous sponge reefs became very common on the northern shelf of the Tethys Ocean where they formed a reef belt 7000 km long at the end of the Jurassic, perhaps the largest reef system to have ever developed on earth. Today hexactinellid sponge reefs exist on the deep continental shelf of western Canada in glacially scoured troughs from 165- 240 m depth. The reefs occur in four complexes, with large (up to 21 m in height) bioherms and vast, low relief meadows. The largest complex is 30 km in length and 15 km wide. The massive reefs have developed over the last 9 ka on the glacially scoured, relict seabed. Development of the reef is dependent on the preferred selection of sponge skeletons by larvae as settling sites, over alternate hard substrate. Different taxa of demosponges are present, both on the reefs as individuals and also as cryptic commensal, epizootic or parasitic sponges that grow on and within hexactinosan skeletons. The sponges baffle and trap sediments from the moderate bottom currents that deliver suspended sediments and nutrients. Seasonal upwelling of nutrient rich slope waters augments shelf productivity in a silicate rich oceanic environment. The sponges form a habitat for many species of fish and invertebrates. Rockfish have been particularly identified as users of sponge habitat and rockfish catches by the deep shelf trawl fishery are often correlated with a large sponge bycatch. Bottom trawling damaged or destroyed reefs in many areas between the late 1940s and 2002, when a trawl closure was implemented.

In the face of growing transplant waitlists and aging donors, sound pre-transplant evaluation of organ offers is paramount. However, many transplant centres lack clear criteria on organ acceptance. Often, previous scores for donor characterisation have not been validated for the Eurotransplant population and are not established to support graft acceptance decisions. Here, we investigated 1353 kidney transplantations at three different German centres to develop and validate novel statistical models for the prediction of early adverse graft outcome (EAO), defined as graft loss or CKD ≥4 within three months. The predictive models use generalised estimating equations (GEE) accounting for potential correlations between paired grafts from the same donor. Discriminative accuracy and calibration were determined via internal and external validation in the development (935 recipients, 309 events) and validation cohort (418 recipients, 162 events) respectively. The expert model is based on predictor ratings by senior transplant nephrologists, while for the data-driven model variables were selected via high-dimensional lasso generalised estimating equations (LassoGee). Both models show moderate discrimination for EAO (C-statistic expert model: 0,699, data-driven model 0,698) with good calibration. In summary, we developed novel statistical models that represent current clinical consensus and are tailored to the older deceased donor population. Compared to KDRI, our described models are sparse with only four and three predictors respectively and account for paired grafts from the same donor, while maintaining a discriminative accuracy equal or better than the established KDRI-score., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2025 Mahler, Friedl, Nusshag, Speer, Benning, Göth, Schaier, Sommerer, Mieth, Mehrabi, Michalski, Renders, Bachmann, Heemann, Krautter, Schwenger, Echterdiek, Zeier, Morath and Kälble.)

Introduction: The impact of deceased donor characteristics on kidney transplant outcomes is controversial. Correspondingly, the predictive performance of deceased donor scores remains moderate, and many transplant centers lack validated criteria for graft acceptance decisions. To better dissect donor-related risk from recipient and periprocedural variables, we analyzed outcomes of kidney donor pairs transplanted in different individuals., Methods: This study explored (a)symmetry of early outcomes of 328 cadaveric kidney transplant recipients from 164 donor pairs transplanted at three Eurotransplant centers. The primary discriminatory factor was (a)symmetry of partner graft function, defined as early graft loss or impaired graft function [estimated glomerular filtration rate (eGFR) <30 mL/min] 3 months after transplantation. We reasoned that a relevant impact of donor factors would result in a high concordance rate of limited graft function or failure., Results: The observed number of symmetric graft failure after transplantation was less than statistically expected (3 months: 1 versus 2, p = 0.89; and 12 months: 3 versus 5, p = 0.26). However, we found a trend toward an impaired 5-year graft survival of grafts with good function 3 months after transplantation but a failed or impaired partner graft compared to symmetrically well-functioning grafts (p = 0.09). Subsequently, we explored the impact of individual donor and recipient variables on early transplant outcomes. Generalized estimating equations after feature selection with LassoGEE bootstrap selected donor age, donor body mass index, and donor eGFR as the relevant risk factors., Discussion: Our findings indicate that donor factors impact early outcomes in kidney transplantation but may have a limited role in long-term graft survival, once a graft has been accepted for transplantation. Utilizing donor-based clinical scores has the potential to aid clinicians in acceptance decisions, giving them an estimate of individual posttransplant outcomes. However, the ultimate decision for acceptance should rest with clinicians, who must consider the complex interplay of donor factors, as well as recipient and periprocedural characteristics., 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 Mahler, Friedl, Nusshag, Speer, Benning, Göth, Schaier, Sommerer, Mieth, Mehrabi, Renders, Heemann, Krautter, Schwenger, Echterdiek, Zeier, Morath and Kälble.)

Background: Kidney graft rejections are classified based on the Banff classification. The RejectClass algorithm, initially derived from a cohort comprising mostly protocol biopsies, identifies data-driven phenotypes of acute rejection and chronic pathology using Banff lesion scores. It also provides composite scores for inflammation activity and chronicity. This study independently evaluates the performance of RejectClass in a cohort consisting entirely of indication biopsies., Methods: We retrospectively applied RejectClass to 441 patients from the German TRABIO (TRAnsplant BIOpsies) cohort who had received indication biopsies. The primary endpoint was death-censored graft failure during 2 y of follow-up., Results: The application of RejectClass to our cohort demonstrated moderately comparable phenotypic features with the derivation cohort, and most clusters indicated an elevated risk of graft loss. However, the reproduction of all phenotypes and the associated risks of graft failure, as depicted in the original studies, was not fully accomplished. In contrast, adjusted Cox proportional hazards analyses substantiated that both the inflammation score and the chronicity score are independently associated with graft loss, exhibiting hazard ratios of 1.7 (95% confidence interval, 1.2-2.3; P = 0.002) and 2.2 (95% confidence interval, 1.8-2.6; P < 0.001), respectively, per 0.25-point increment (scale: 0.0-1.0)., Conclusions: The composite inflammation and chronicity scores may already have direct utility in quantitatively assessing the disease stage. Further refinement and validation of RejectClass clusters are necessary to achieve more reliable and accurate phenotyping of rejection., Competing Interests: F.A.v.S.-H. and B.K. are supported by the Medical Faculty of the Christian-Albrechts-University Kiel. J.H.B. and J.S. were supported by the Federal Ministry of Education and Research 
(Bundesministerium für Bildung und Forschung [BMBF], KMU-innovativ: grant 13GW0399B). H.U.Z. was supported by the BMBF within the framework of the e:Med research and funding concept (grant 01ZX1912A). The other authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The administration of modified immune cells (MIC) before kidney transplantation led to specific immunosuppression against the allogeneic donor and a significant increase in regulatory B lymphocytes. We wondered how this approach affected the continued clinical course of these patients., Methods: Ten patients from a phase I clinical trial who had received MIC infusions prior to kidney transplantation were retrospectively compared to 15 matched standard-risk recipients. Follow-up was until year five after surgery., Results: The 10 MIC patients had an excellent clinical course with stable kidney graft function, no donor-specific human leukocyte antigen antibodies (DSA) or acute rejections, and no opportunistic infections. In comparison, a retrospectively matched control group receiving standard immunosuppressive therapy had a higher frequency of DSA (log rank P = 0.046) and more opportunistic infections (log rank P = 0.033). Importantly, MIC patients, and in particular the four patients who had received the highest cell number 7 days before surgery and received low immunosuppression during follow-up, continued to show a lack of anti-donor T lymphocyte reactivity in vitro and high CD19 + CD24 hi CD38 hi transitional and CD19 + CD24 hi CD27 + memory B lymphocytes until year five after surgery., Conclusions: MIC infusions together with reduced conventional immunosuppression were associated with good graft function during five years of follow-up, no de novo DSA development and no opportunistic infections. In the future, MIC infusions might contribute to graft protection while reducing the side effects of immunosuppressive therapy. However, this approach needs further validation in direct comparison with prospective controls., Trial Registration: https://clinicaltrials.gov/, identifier NCT02560220 (for the TOL-1 Study). EudraCT Number: 2014-002086-30., Competing Interests: MSa, CMo, CK, GO, MZ, MSm, PT, and ASm together with the University of Heidelberg, are co-founders of TolerogenixX GmbH, Heidelberg, Germany, a biotechnology company that holds licenses for MIC treatment. CK, GO, and PT hold a patent for MIC treatment. MSa, CMo, CK, GO, CSü, MZ, MSm, PT, AS, and VD together with the University of Heidelberg and TolerogenixX GmbH filed a patent application for MIC treatment. The remaining 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 Schaier, Morath, Wang, Kleist, Opelz, Tran, Scherer, Pham, Ekpoom, Süsal, Ponath, Kälble, Speer, Benning, Nusshag, Mahler, Pego da Silva, Sommerer, Hückelhoven-Krauss, Czock, Mehrabi, Schwab, Waldherr, Schnitzler, Merle, Schwenger, Krautter, Kemmner, Fischereder, Stangl, Hauser, Kälsch, Krämer, Böhmig, Müller-Tidow, Reiser, Zeier, Schmitt, Terness, Schmitt and Daniel.)

Introduction: Despite continued efforts, long-term outcomes of kidney transplantation remain unsatisfactory. Kidney graft rejections are independent risk factors for graft failure. At the participating centres of the TRAnsplant BIOpsies study group, a common therapeutic standard has previously been defined for the treatment of graft rejections. The outcomes of this strategy will be assessed in a prospective, observational cohort study., Methods and Analysis: A total of 800 kidney transplantation patients will be enrolled who undergo a graft biopsy because of deteriorating kidney function. Patients will be stratified according to the Banff classification, and the influence of the treatment strategy on end points will be assessed using regression analysis. Primary end points will be all-cause mortality and graft survival. Secondary end points will be worsening of kidney function (≥30% decline of estimated Glomerular Filtration Rate [eGFR] or new-onset large proteinuria), recurrence of graft rejection and treatment response. Baseline data and detailed histopathology data will be entered into an electronic database on enrolment. During a first follow-up period (within 14 days) and subsequent yearly follow-ups (for 5 years), treatment strategies and clinical course will be recorded. Recruitment at the four participating centres started in September 2016. As of August 2020, 495 patients have been included., Ethics and Dissemination: Ethical approval for the study has been obtained from the ethics committee of Kiel (AZ B 278/16) and was confirmed by the committees of Munich, Mainz and Stuttgart. The results will be reported in a peer-reviewed journal, according to the Strengthening the Reporting of Observational Studies in Epidemiology criteria., Trial Registration Number: ISRCTN78772632; Pre-results., Competing Interests: Competing interests: JW-M has received research support from GSK, DIAMED, Miltenyi Biotech as well as personal fees from Novartis, GSK, Boehringer-Ingelheim, Miltenyi, Vifor and Chiesi (all unrelated to the submitted work)., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The insecticidal crystal proteins from Bacillus thuringiensis (Bt) are widely-used biopesticides that are used both as Bt spore-crystal preparations in sprayable formulations and as activated toxins in genetically modified (GM) plants. Models for their modes of action have been proposed but many issues remain unresolved. Among those is the role of commensal gut bacteria in target insect death: previous studies showed that antibiotics attenuate the toxicity of Bt sprays. We tested whether antibiotics interfere with the effects of GM plant-produced Bt toxins in larvae of two Lepidopteran species, the European corn borer Ostrinia nubilalis and the cotton leafworm Spodoptera littoralis . The larvae were reared on artificial diet with or without antibiotics and, thereafter, fed two varieties of Bt GM maize in comparison to conventional non-Bt maize leaves sprayed with antibiotic solution and/or with a Bt formulation. Antibiotics significantly reduced or delayed the toxicity of Cry toxins, although to a lesser extent than previously reported for Bt-sprays. This supports the hypothesis that Cry toxins induce mortality by themselves in the absence of Bt bacteria and spores, and of commensal gut bacteria. However, larvae that were not treated with antibiotics died faster and at a higher rate which was further compounded by plant variety and species sensitivity. These findings support a hypothesis that toxicemia alone can inflict significant mortality. However, in the absence of antibiotics, the gut bacteria likely enhance the Cry toxin effect by inflicting, additionally, bacterial septicemia. This has important implications in field situations where antibiotic substances are present-e.g., from manure of animals from conventional production systems-and for ecotoxicological testing schemes of Bt toxins and nontarget organisms that are often using artificial diets enriched with high concentrations of antibiotics.

Background: Standardized patients are widely used in training of medical students, both in teaching and assessment. They also frequently lead complete training sessions delivering physical examination skills without the aid of faculty teaching staff-acting as "patient instructors" (PIs). An important part of this training is their ability to provide detailed structured feedback to students which has a strong impact on their learning success. Yet, to date no study has assessed the quality of physical examination related feedback by PIs. Therefore, we conducted a randomized controlled study comparing feedback of PIs and faculty staff following a physical examination assessed by students and video assessors., Methods: 14 PIs and 14 different faculty staff physicians both delivered feedback to 40 medical students that had performed a physical examination on the respective PI while the physicians observed the performance. The physical examination was rated by two independent video assessors to provide an objective performance standard (gold standard). Feedback of PI and physicians was content analyzed by two different independent video assessors based on a provided checklist and compared to the performance standard. Feedback of PIs and physicians was also rated by medical students and video assessors using a questionnaire consisting of 12 items., Results: There was no statistical significant difference concerning overall matching of physician or PI feedback with gold standard ratings by video assessment (p = .219). There was also no statistical difference when focusing only on items that were classified as major key steps (p = .802), mistakes or parts that were left out during physical examination (p = .219) or mistakes in communication items (p = .517). The feedback of physicians was significantly better rated than PI feedback both by students (p = .043) as well as by video assessors (p = .034)., Conclusions: In summary, our study demonstrates that trained PIs are able to provide feedback of equal quantitative value to that of faculty staff physicians with regard to a physical examination performed on them. However, both the students and the video raters judged the quality of the feedback given by the physicians to be significantly better than that of the PIs.

Background: Redundant training and feedback are crucial for successful acquisition of skills in simulation trainings. It is still unclear how or how much feedback should best be delivered to maximize its effect, and how learners' activity and feedback are optimally blended. To determine the influence of high- versus low-frequency expert feedback on the learning curve of students' clinical procedural skill acquisition in a prospective randomized study., Methods: N = 47 medical students were trained to insert a nasogastric tube in a mannequin, including structured feedback in the initial instruction phase at the beginning of the training (T1), and either additional repetitive feedback after each of their five subsequent repetitions (high-frequency feedback group, HFF group; N = 23) or additional feedback on just one occasion, after the fifth repetition only (low-frequency feedback group, LFF group; N = 24). We assessed a) task-specific clinical skill performance and b) global procedural performance (five items of the Integrated Procedural Performance Instrument (IPPI); on the basis of expert-rated videotapes at the beginning of the training (T1) and during the final, sixth trial (T2)., Results: The two study groups did not differ regarding their baseline data. The calculated ANOVA for task-specific clinical skill performance with the between-subject factor 'Group' (HFF vs. LFF) and within-subject factors 'Time' (T1 vs. T2) turned out not to be significant (p < .147). An exploratory post-hoc analyses revealed a trend towards a superior performance of HFF compared to LFF after the training (T2; p < .093), whereas both groups did not differ at the beginning (T1; p < .851). The smoothness of the procedure assessed as global procedural performance, was superior in HFF compared to LFF after the training (T2; p < .004), whereas groups did not differ at the beginning (T1; p < .941)., Conclusion: Deliberate practice with both high- and low-frequency intermittent feedback results in a strong improvement of students' early procedural skill acquisition. High-frequency intermittent feedback, however, results in even better and smoother performance. We discuss the potential role of the cognitive workload on the results. We advocate a thoughtful allocation of tutor resources to future skills training.

Background: Physical clinical examination is a core clinical competence of medical doctors. In this regard, digital rectal examination (DRE) plays a central role in the detection of abnormalities of the anus and rectum. However, studies in undergraduate medical students as well as newly graduated doctors show that they are insufficiently prepared for performing DRE. Training units with Standardized Patients (SP) represent one method to deliver DRE skills. As yet, however, it is little known about SPs' attitudes., Methods: This is a qualitative study using a grounded theory approach. Interviews were conducted with 4 standardized patients about their experiences before, during and after structured SP training to deliver DRE competencies to medical students. The resulting data were subjected to thematic content analysis., Results: Results show that SPs do not have any predominant motives for DRE program participation. They participate in the SP training sessions with relatively little prejudice and do not anticipate feeling highly vulnerable within teaching sessions with undergraduate medical students., Conclusions: The current study examined SPs' motives, views, expectations and experiences regarding a DRE program during their first SP training experiences. The results enabled us to derive distinct action guidelines for the recruitment, informing and briefing of SPs who are willing to participate in a DRE program.

Background: The physical examination of patients is an important diagnostic competence, but little is known about the examination skills of final-year medical students., Aims: To investigate physical examination skills of final-year medical students., Methods: In a cross-sectional study, 40 final-year students were asked to perform a detailed physical examination on standardized patients. Their performances were video-recorded and rated by independent video assessors., Results: Video ratings showed a mean success rate of 40.1 % (SD 8.2). As regards accompanying doctor-patient communication, final-year students achieved a mean of no more than 36.7 % (SD 8.9) in the appropriate use of the corresponding communication items., Conclusions: Our study revealed severe deficits among final-year medical students in performing a detailed physical examination on a standardized patient. Thus, physical examination skills training should aim to improve these deficits while also paying attention to communicative aspects., (Copyright © 2015. Published by Elsevier GmbH.)