A pig kidney supporting human physiology.

Because of the global shortage of donor kidneys, xenotransplantation emerges as a potential solution for individuals with kidney failure who face challenges in securing a suitable donor kidney. A study featured in this month's issue of Kidney International assesses the kidney physiology of a porcine kidney transplanted into a brain-dead human with kidney failure, demonstrating life-sustaining physiological function for 7 days. Together with preclinical nonhuman primate studies, decedent models provide complementary data for development of clinical kidney xenotransplantation.

Late graft failure of pig-to-rhesus renal xenografts has features of glomerulopathy and recipients have anti-swine leukocyte antigen class I and class II antibodies.

Prolonged survival in preclinical renal xenotransplantation demonstrates that early antibody mediated rejection (AMR) can be overcome. It is now critical to evaluate and understand the pathobiology of late graft failure and devise new means to improve post xenograft outcomes. In renal allotransplantation the most common cause of late renal graft failure is transplant glomerulopathy-largely due to anti-donor MHC antibodies, particularly anti-HLA DQ antibodies. We evaluated the pig renal xenograft pathology of four long-surviving (>300 days) rhesus monkeys. We also evaluated the terminal serum for the presence of anti-SLA class I and specifically anti-SLA DQ antibodies. All four recipients had transplant glomerulopathy and expressed anti-SLA DQ antibodies. In one recipient tested for anti-SLA I antibodies, the recipient had antibodies specifically reacting with two of three SLA I alleles tested. These results suggest that similar to allotransplantation, anti-MHC antibodies, particularly anti-SLA DQ, may be a barrier to improved long-term xenograft outcomes.

The Surgical Clerkship in the COVID Era: A Natural Language Processing and Thematic Analysis.

INTRODUCTION: Responses to COVID-19 within medical education prompted significant changes to the surgical clerkship. We analyzed the changes in medical student end of course feedback before and after the COVID-19 outbreak. METHODS: Postclerkship surveys from 2017 to 2022 were analyzed including both Likert scale data and free text, excluding the COVID outbreak year 2019-2020. Likert scale questions were compared between pre-COVID (2017-2019) and COVID-era cohorts (2020-2022) with the Mann-Whitney U-test. Free-text comments were analyzed using both thematic analysis and natural language processing including sentiment, word and phrase frequency, and topic modeling. RESULTS: Of the 483 medical students surveyed from 2017 to 2022, 297 responded (61% response rate) to the included end of clerkship surveys. Most medical students rated the clerkship above average or excellent with no significant difference between the pre-COVID and COVID-era cohorts (70.4% Versus 64.8%, P = 0.35). Perception of grading expectations did significantly differ, 51% of pre-COVID students reported clerkship grading standards were almost always clear compared to 27.5% of COVID-era students (P = 0.01). Pre-COVID cohorts more frequently mentioned learning and feedback while COVID-era cohorts more frequently mentioned case, attending, and expectation. Natural language processing topic modeling and formal thematic analysis identified similar themes: team, time, autonomy, and expectations. CONCLUSIONS: COVID-19 presented many challenges to undergraduate medical education. Despite many changes, there was no significant difference in clerkship satisfaction ratings. Unexpectedly, the greater freedom and autonomy of asynchronous lectures and choice of cases became a highlight of the new curriculum. Future research should investigate if there are similar associations nationally with a multi-institutional study.

Prior Teaching Experience and Barriers to Effective Resident Teaching: A Cross-Sectional Study.

INTRODUCTION: Resident physicians play an important role in teaching the next generation of health-care providers, yet limited research has explored factors influencing effective teaching, such as preresidency experiences or barriers within residency. This study examines residents' prior teaching experience, its correlation with teaching attitudes, and identifies potential barriers to sustained teaching engagement. METHODS: This cross-sectional study surveyed residents across multiple specialties at a single academic center. The survey assessed preresidency teaching experience, perceived barriers, and attitudes toward teaching. Univariate and multivariate analyses identified differences in teaching attitudes based on prior teaching experience and gender. RESULTS: Ninety-two residents across 11 specialties participated (52.2% female). Internal Medicine (28.3%) and General Surgery (26.1%) had the highest representation. Two-thirds of respondents (69.6%) had formal teaching experience before residency. After adjustment, prior teaching experience and male gender were associated with feeling prepared to teach medical students (P = 0.014 and P = 0.001). Male gender was also linked to confidence in teaching material on the wards (P = 0.015). Barriers identified included time constraints (73.9%), lack of content clarity (28.3%), and uncertainty about teaching methods (33.7%). CONCLUSIONS: Residents with prior teaching experience exhibit higher levels of preparedness, content clarity, and confidence in their teaching abilities, underscoring the importance of teaching experience before residency. This study also identified significant barriers to effective teaching, including time constraints, lack of content clarity, uncertainty about teaching methods, and perceived disinterest from medical students. Addressing these barriers is essential for optimizing medical student education.

Surgical Residents as Clerkship Scholars May Improve Student Perception of the Surgery Clerkship.

INTRODUCTION: The surgical clerkship is a formative experience in the medical school curriculum and can leave a lasting impression on students' perception of surgery. Given the historical negative stereotypes of surgeons, the clerkship represents an opportunity to impact students in a meaningful way. METHODS: Our institution developed a program in which research residents can serve as junior clerkship coordinators and educators; working closely with medical students on their surgery clerkship. At the end of their clerkship, students were administered a survey with Likert-scale and free text responses regarding satisfaction with the rotation, lectures, feedback, and value of the clerkship. Student survey results were compared before (2015-2016) and after (2017-2019) the implementation of the scholar program with nonparametric statistical analysis and qualitative text analysis. RESULTS: A total of 413 students responded to the survey with no significant difference in response rate by term (P = 0.88). We found no statistical difference with respect to overall course perception (92.3% versus 91.2%, P = 0.84), but a statistically significant difference was noted for the clarity of the provided written clerkship materials (80.3% versus 91.3%, P = 0.02) and usefulness of the feedback (57.5% versus 78.7%, P = 0.01). Qualitative analysis demonstrated an overall positive shift in perception of the clerkship, improvement in the course materials, and organization. CONCLUSIONS: The scholar program was overall well received by the students with improvements in certain aspects of the clerkship: organization, feedback, and course materials. This program represents a potential strategy to improve certain portions of the medical school clerkship experience.

The Association Between Altmetric Attention Scores and Public Engagement in the Medical Literature.

INTRODUCTION: With the advent of social media and the associated increase in connectivity between scientists and the lay public, the Altmetric Attention Score has been created as a way to measure these interactions between scholarly publications and media dissemination. Little is known, however, whether these types of media exchanges measured by Altmetrics may serve as a proxy for public engagement. As such, we have sought to determine whether or not an association exists between Altmetric scores and public engagement, as measured by article citation in a health policy document. METHODS: The top 100 highest scoring articles in the medical and health sciences with respect to Altmetric Attention Scores were selected from each of 3 y (2014, 2015, and 2016). Each article was then matched to an article from the same year and journal with the highest Relative Citation Ratio (RCR) for comparison. Bivariate analysis compared article groups with respect to citation in a public policy document, open-access status, and funding status, as well as Altmetric and RCR scores. A multivariable model was then constructed to identify significant factors associated with citation in a public policy document. Finally, a contour plot was generated in order to estimate the interaction between Altmetric Scores and RCR and their comparative effects on the probability of inclusion in a health policy document. RESULTS: Of the 600 articles included in the analysis, 286 (48%) had been cited by a public policy article. The only difference that existed between the cohorts was for funding status, with 55 articles (40%) in the RCR cohort having received funding compared to 81 (60%) in the Altmetric cohort (P = 0.011). On bivariate analysis, both Altmetric (P = 0.0018) and RCR (P < 0.0001) scores were independently predictive of policy citation. In a multivariable model, the interaction between Altmetric Scores and RCR with respect to policy inclusion was significant (OR = 1.22; 95% CI = 1.08-1.38) and a contour plot demonstrates that either high Altmetric score or RCR alone is sufficient to generate a high probability of policy inclusion. CONCLUSIONS: Scholarly article Altmetric Scores may serve as a novel means to explore public engagement in scientific research and health policy. In addition, journals that aim to impact public policy through article dissemination may benefit from engagement in social media avenues in addition to traditional citation pathways in order to encourage broader inclusion.

The Influence of an Acting or Subintern on Third-Year Medical School Surgery Clerkship Students.

BACKGROUND: Previous reports demonstrated a positive relationship between the surgical clerkship and student likelihood of pursuing a surgical career, but no studies have examined the influence a peer has on comfort during a surgical clerkship. We hypothesized that a fourth-year acting intern (AI) would positively impact third-year medical students' experience during their surgical clerkship. METHODS: All third-year medical students at our institution who completed their surgical clerkship in 2019 were surveyed regarding the preclerkship and postclerkship perceptions. RESULTS: Of the 110 students surveyed, 52 responded (47.3% response rate), and 25 students (48.1%) reported having an AI during their clerkship rotation, and 27 did not (51.9%). Presence of an AI had no significant effect on the postclerkship perception of surgery, likelihood of pursuing general surgery, or comfort in the OR. Analysis of all responses demonstrated the surgery clerkship had no significant impact on students' perception of surgery or likelihood of pursuing general surgery but did statistically increase students' comfort in the OR. CONCLUSIONS: The results of this study suggest that AI presence did not significantly influence a student's clerkship experience or comfort in the OR. Further studies are needed to determine what, if any effect, an AI could have on third-year clerkship students.

Efficacy of ATG and Rituximab in capuchin monkeys (a New World monkey)-An in vitro study relevant to xenotransplantation.

While Old World monkeys, for example, baboons, have antibodies against triple-knockout (TKO) pig cells, thus complicating pig organ transplantation studies, capuchin monkeys (a New World monkey) do not, thus more closely mimicking humans in respect to the response to TKO pig cells. Whether drugs such as anti-thymocyte globulin (ATG) and Rituximab are effective in capuchin monkeys remains uncertain. We measured the binding and cytotoxicity of ATG and Rituximab to human (n = 7), baboon (n = 7), and capuchin monkey (n = 5) peripheral blood mononuclear cells (PBMCs), T cells or B cells by flow cytometry.The effect in vitro of ATG in depleting PBMCs in capuchin monkeys and baboons was significantly less than in humans, but the depletion in capuchin monkeys was not significantly different from that in baboons. In contrast, the effect in vitro of Rituximab in depleting B cells in capuchin monkeys was very limited, and significantly less than in humans and baboons.Although capuchin monkeys mimic the human antibody response to TKO pig cells more closely than baboons, Rituximab had a minimal effect in capuchin monkeys in vitro. This observation may limit the value of New World Monkeys as recipients of pig organs, tissues, or cells in experimental studies of xenotransplantation or, indeed, in allotransplantation.

Examining the Biosynthesis and Xenoantigenicity of Class II Swine Leukocyte Antigen Proteins.

Genetically engineered pig organs could provide transplants to all patients with end-stage organ failure, but Ab-mediated rejection remains an issue. This study examines the class II swine leukocyte Ag (SLA) as a target of epitope-restricted Ab binding. Transfection of individual α- and ß-chains into human embryonic kidney cells resulted in both traditional and hybrid class II SLA molecules. Sera from individuals on the solid organ transplant waiting list were tested for Ab binding and cytotoxicity to this panel of class II SLA single-Ag cells. A series of elution studies from an SLA-DQ cell line were performed. Our results indicate that human sera contain Abs specific for and cytotoxic against class II SLA. Our elution studies revealed that sera bind the SLA-DQ molecule in an epitope-restricted pattern. Site-specific mutation of one of these epitopes resulted in statistically decreased Ab binding. Humans possess preformed, specific, and cytotoxic Abs to class II SLA that bind in an epitope-restricted fashion. Site-specific epitope mutagenesis may decrease the Ab binding of highly sensitized individuals to pig cells.

Examining epitope mutagenesis as a strategy to reduce and eliminate human antibody binding to class II swine leukocyte antigens.

Xenotransplantation of pig organs into people may help alleviate the critical shortage of donors which faces organ transplantation. Unfortunately, human antibodies vigorously attack pig tissues preventing the clinical application of xenotransplantation. The swine leukocyte antigens (SLA), homologs of human HLA molecules, can be xenoantigens. SLA molecules, encoded by genes in the pig major histocompatibility complex, contribute to protective immune responses in pig. Therefore, simply inactivating them through genome engineering could reduce the ability of the human immune system to surveil transplanted pig organs for infectious disease or the development of neoplasms. A potential solution to this problem is to identify and modify epitopes in SLA proteins to eliminate their contribution to humoral xenoantigenicity while retaining their biosynthetic competence and ability to contribute to protective immunity. We previously showed that class II SLA proteins were recognized as xenoantigens and mutating arginine at position 55 to proline, in an SLA-DQ beta chain, could reduce human antibody binding. Here, we extend these observations by creating several additional point mutants at position 55. Using a panel of monoclonal antibodies specific for class II SLA proteins, we show that these mutants remain biosynthetically competent. Examining antibody binding to these variants shows that point mutagenesis can reduce, eliminate, or increase antibody binding to class II SLA proteins. Individual mutations can have opposite effects on antibody binding when comparing samples from different people. We also performed a preliminary analysis of creating point mutants near to position 55 to demonstrate that manipulating additional residues also affects antibody reactivity.