Surgical regret often experienced at times of a great loss may cause a surgeon to reflect on their practice and intraoperative decision-making. It is inevitable that in the surgical profession, both in training and practice, a surgeon's decisions will be questioned by themselves, peers, and possibly patients. Here, we explore a case of living donor kidney donation in which the surgeon chooses to discontinue the operation for an incidental finding. Ultimately, this is against the patient's wishes and a decision over which both the surgeon and patient experience moral hazard and regret. This article explores surgical regret from the lens of an altruistic donor case and a surgeon's inaction, discussing the ethics of the operative decision-making and surgeon's viewpoint intra- and post-operatively.

In 1994, to guide patients and surgeons in making informed decisions about organ transplantation and reduce transplant-mediated infectious disease transmission, the Centers for Disease Control and Prevention announced the Public Health Service guidelines for increased risk donor (IRD) organs. This classification identifies donors associated with greater risk for contracting human immunodeficiency virus, hepatitis B virus, and hepatitis C virus as increased risk donors. These donor organs are discarded at higher rates than non-IRD organs, despite equivalent patient and graft survival rates following transplantation. Biases and stigmas, as well as misunderstandings about the term “increased risk,” may contribute to the discard of these high-quality organs. Novel communication strategies regarding the risk of disease transmission from IRD organs are needed to reduce misunderstandings between patients and providers and shift the conversation from probabilities and statistics to patient-centered values and expectations. Using a standardized tool such as Best Case/Worst Case to elicit patients’ preferences and share expected outcomes of accepting versus rejecting an IRD organ has the potential to improve IRD risk communication. The purpose of this article is to elucidate the underutilization of IRD organs, through the example of a potential kidney transplantation, to demystify this complex and high-stakes decision utilizing a novel communication strategy and to propose policy changes to IRD organ management that could result in hundreds of additional lives saved each year.

Background Hernias in patients with ascites are common, however we know very little about the surgical repair of hernias within this population. The study of these repairs has largely remained limited to single center and case studies, lacking a population-based study on the topic. Study design The Michigan Surgical Quality Collaborative and its corresponding Core Optimization Hernia Registry (MSQC-COHR) which captures specific patient, hernia, and operative characteristics at a population level within the state was used to conduct a retrospective review of patients with ascites undergoing ventral or inguinal hernia repair between January 1, 2020 and May 3, 2022. The primary outcome observed was incidence and surgical approach for both ventral and inguinal hernia cohorts. Secondary outcomes included 30-day adverse clinical outcomes as listed here: (ED visits, readmission, reoperation and complications) and surgical priority (urgent/emergent vs elective). Results In a cohort of 176 patients with ascites, surgical repair of hernias in patients with ascites is a rare event (1.4% in ventral hernia cohort, 0.2% in inguinal hernia cohort). The post-operative 30-day adverse clinical outcomes in both cohorts were greatly increased compared to those without ascites (ventral: 32% inguinal: 30%). Readmission was the most common complication in both inguinal (n = 14, 15.9%) and ventral hernia (n = 17, 19.3%) groups. Although open repair was most common for both cohorts (ventral: 86%, open: 77%), minimally invasive (MIS) approaches were utilized. Ventral hernias presented most commonly urgently/emergently (60%), and in contrast many inguinal hernias presented electively (72%). Conclusion A population-level, ventral and incisional hernia database capturing operative details for 176 patients with ascites. There was variation in the surgical approaches performed for this rare event and opportunities for optimization in patient selection and timing of repair.

A lack of federal access to health-care resources for undocumented immigrants in the USA has led to variability in access to health care — including dialysis — across states. Transforming dialysis care for these individuals is justified both on humanitarian and economic grounds, but requires a roadmap for advocacy and stakeholder engagement.

IntroductionCircumcision is a common procedure that can evoke caregiver anxiety in the postoperative period due to unfamiliarity with the healing process. To mitigate unnecessary healthcare utilization such as phone calls and unanticipated clinic or emergency department (ED) visits, photographic atlases have been developed to better prepare caregivers for the recovery process. The objective of our study is to further investigate the efficacy of a photographic atlas in its ability to decrease postoperative healthcare utilization using an increased sample size and extended study period compared to previous studies. Materials and methodsIn this study, we compared a prospective intervention cohort of patients undergoing circumcision at our institution who received a photographic atlas during postoperative teaching to a retrospective cohort of patients who had not received it. Our primary outcome was unanticipated healthcare utilization, defined as postoperative telephone calls and unanticipated presentations to the urology clinic or ED.ResultsThe retrospective no-atlas cohort included 105 pa-tients, and the prospective intervention atlas cohort included 80 patients. Both groups were similar with respect to age (p = 0.47) and other demographics.There was no statistically significant difference in healthcare utilization between the no-atlas and atlas cohort. Specifically, we identified no differ-ence in the number of phone calls to clinic staff (12 [11.4%] vs. 11 [13.8%], p = 0.64) or unanticipated postoperative clinic or ED visits (2 [1.9%] vs. 4 [5.0%], p = 0.41). DiscussionThe use of a photographic atlas as part of caregiver support for circumcision patients did not demon-strate a statistically significant reduction in either postoperative phone calls or clinic/ED visits. The decrease in absolute number of caregiver phone calls was minimal (12-11), with a small increase in follow-up presentations (2-4). The lack of signifi-cant change may be due to the already infrequent occurrence of these events following circumcision, as demonstrated by the no-atlas cohort. Other po-tential advantages of the atlas, such as improved caregiver confidence and satisfaction, may have been present, but were not measured in this study.ConclusionsAdding to the mixed results of previous studies, these findings do not support that photographic atlases decrease unanticipated healthcare utiliza-tion in children undergoing a circumcision. However, utilization was found to be low. Additionally, further studies are needed to determine other significant benefits of this form of education, such as improved caregiver confidence and satisfaction.

Donation after circulatory death (DCD) has an important role in organ transplantation. The number of DCD transplants has consistently grown on an annual basis, and DCD outcomes continue to show improvement. Yet, the protocols that have been adopted and codified to control this practice exhibit variability. In the United States, Organ Procurement Organizations (OPOs) as well as transplantation professional societies have made official recommendations for DCD practices. Donation after circulatory death recoveries occur after a specified observation period after which the donor is declared dead for which the American Society of Transplant Surgeons (ASTS) recommends 2 minutes. Their recommendation was made to not unnecessarily increase warm ischemia time but also recognizes that there is limited data on auto-resuscitation. The American Society of Transplant Surgeons has also published recommended practice guidelines to administer heparin prior to the withdrawal of support but did not state a specific dosage, allowing for the possibility of variation in practice. Premortem administration of heparin has shown to improve organ function, reducing rates of primary nonfunction in DCD liver transplants, as well as improved graft survival. Concerns were previously raised that anticoagulants, such as heparin, posed a risk to the donor.6–8 Upon review, ASTS determined there was a lack of evidence that heparin hastened death in cases where there was no ongoing intracranial bleed nor deficiency in blood volume. While national society guidelines are provided, they do not govern individual hospitals or OPOs. Organ procurement organization recommendations differ from region to region and within each geographic donor service area (DSA). Individual hospitals have an internal decision on their observation periods and use of premortem anticoagulants — aspects relevant for optimizing graft function in the recipient. Variability of DCD practices has been demonstrated in a national study of OPO guidelines as well a national study of children’s hospitals. The variability of the policies surrounding DCD suggests that individual hospitals reach different conclusions about the ethics and scientific data that inform premortem interventions and observation periods for a DCD donor. For example, where along a continuum of heparin administration and dosages as well as observation period time intervals in which a threshold is crossed that might violate the Dead Donor Rule and individual institutions’ values. Lack of standardization across policies could create problems amongst a shared resource. This may result in less trust among institutions that recover and receive organs, more room for error for traveling transplant surgeons and team members in recovery operations, and inconsistencies in DCD data. This variance could result in organs deemed unusable and lives lost. We evaluated adult hospital DCD policies within the state of Michigan for observation periods that follow ASTS guidelines, administration of premortem heparin and the policy’s stated rationales. Through the process of comparing policies across the state, we intended to provide additional data on adult hospital DCD policy variation and identify areas for improvement.

New approaches are needed to reduce disparities in access to kidney transplantation. Telemedicine provides an opportunity to address inequities in access to care, with many services transitioning to virtual platforms during the coronavirus disease 2019 (COVID-19) pandemic.1Bashshur R.L. Shannon G.W. Krupinski E.A. et al.National telemedicine initiatives: essential to healthcare reform.Telemed J E Health. 2009; 15: 600-610Crossref PubMed Scopus (98) Google Scholar Intentional, collaborative, and community-led interventions that go beyond maintaining existing services are essential to overcome deeply rooted barriers to care. Dialysis facilities in particular are well positioned to increase access to kidney transplantation. The hours that patients spend to attend regular hemodialysis sessions could be used to conduct video visits with transplant providers. Telemedicine collaborations between transplant centers and dialysis facilities could increase equitable access to transplantation services by improving education, increasing transplant referrals, and expanding transplant evaluations for underserved populations. Kidney transplantation improves long-term outcomes over dialysis, yet 4 out of 5 patients with kidney failure in the United States are not waitlisted for kidney transplant.2Patzer R.E. Pastan S.O. Policies to promote timely referral for kidney transplantation.Semin Dial. 2020; 33: 58-67Crossref PubMed Scopus (3) Google Scholar Examples of inequities exist at every stage of the transplant process, and dedicated resources are needed to eliminate the influence of systemic racism.3Pullen L.C. Striving for equity in transplant.Am J Transplant. 2020; 20: 2293-2294Crossref PubMed Scopus (3) Google Scholar African Americans are 37% less likely than White patients to be referred for transplant evaluation prior to initiation of dialysis.2Patzer R.E. Pastan S.O. Policies to promote timely referral for kidney transplantation.Semin Dial. 2020; 33: 58-67Crossref PubMed Scopus (3) Google Scholar Non–English-speaking patients are less likely to complete the evaluation process and become active on the waitlist.4Talamantes E. Norris K.C. Mangione C.M. et al.Linguistic isolation and access to the active kidney transplant waiting list in the United States.Clin J Am Soc Nephrol. 2017; 12: 483-492Crossref PubMed Scopus (17) Google Scholar Patients who are White, male, and of higher socioeconomic status have increased access to kidney transplantation, despite rates of kidney failure in African Americans being 3 times higher.2Patzer R.E. Pastan S.O. Policies to promote timely referral for kidney transplantation.Semin Dial. 2020; 33: 58-67Crossref PubMed Scopus (3) Google Scholar,5Centers for Disease Control and Prevention; Department of Health and Human ServicesChronic Kidney Disease in the United States, 2019.2019https://www.cdc.gov/kidneydisease/pdf/2019_National-Chronic-Kidney-Disease-Fact-Sheet.pdfGoogle Scholar Average dialysis facility transplant rates vary well over 2-fold depending on geographic location, with lower rates seen in centers with higher proportions of African American patients.6Patzer R.E. Plantinga L. Krisher J. Pastan S.O. Dialysis facility and network factors associated with low kidney transplantation rates among United States dialysis facilities.Am J Transplant. 2014; 14: 1562-1572Crossref PubMed Scopus (52) Google Scholar African Americans have kidney transplant rates 59% lower than White patients and are 70% less likely to receive a living donor transplant.7Patzer R.E. Perryman J.P. Schrager J.D. et al.The role of race and poverty on steps to kidney transplantation in the Southeastern United States.Am J Transplant. 2012; 12: 358-368Crossref PubMed Scopus (86) Google Scholar,8Gander J.C. Zhang X. Plantinga L. et al.Racial disparities in preemptive referral for kidney transplantation in Georgia.Clin Transplant. 2018; 32e13380Crossref PubMed Scopus (22) Google Scholar Substantial barriers arise from under-resourced or uninformed providers. Dialysis facilities with fewer social workers have reduced referral rates.2Patzer R.E. Pastan S.O. Policies to promote timely referral for kidney transplantation.Semin Dial. 2020; 33: 58-67Crossref PubMed Scopus (3) Google Scholar Despite evidence of better outcomes with kidney transplantation, nephrologists are less likely to place a referral if they feel their patient is doing well on dialysis, and fewer than 20% think their patient is interested in a transplant evaluation.2Patzer R.E. Pastan S.O. Policies to promote timely referral for kidney transplantation.Semin Dial. 2020; 33: 58-67Crossref PubMed Scopus (3) Google Scholar,9Lipford K.J. McPherson L. Hamoda R. et al.Dialysis facility staff perceptions of racial, gender, and age disparities in access to renal transplantation.BMC Nephrol. 2018; 19: 5Crossref PubMed Scopus (14) Google Scholar A study published in 2018 reported that 40% of dialysis facility administrators were not aware of changes in the Kidney Allocation System (KAS) implemented in 2014, and that 81% of providers were not aware of disparities in kidney transplant waitlisting.9Lipford K.J. McPherson L. Hamoda R. et al.Dialysis facility staff perceptions of racial, gender, and age disparities in access to renal transplantation.BMC Nephrol. 2018; 19: 5Crossref PubMed Scopus (14) Google Scholar Finally, some providers feel that nonadherent patients should not be waitlisted.2Patzer R.E. Pastan S.O. Policies to promote timely referral for kidney transplantation.Semin Dial. 2020; 33: 58-67Crossref PubMed Scopus (3) Google Scholar At the patient level, sociocultural factors such as medical mistrust, patient-reported racism, and experienced discrimination are also associated with inequitable access to kidney transplant evaluation.10Hamoda R.E. McPherson L.J. Lipford K. et al.Association of sociocultural factors with initiation of the kidney transplant evaluation process.Am J Transplant. 2020; 20: 190-203Crossref PubMed Scopus (13) Google Scholar Even when a referral does occur, low transplant literacy, race, and sex have been associated with failure of evaluation completion or appointment attendance.11Monson R.S. Kemerley P. Walczak D. Benedetti E. Oberholzer J. Danielson K.K. Disparities in completion rates of the medical prerenal transplant evaluation by race or ethnicity and gender.Transplantation. 2015; 99: 236-242Crossref PubMed Scopus (29) Google Scholar,12Dageforde L.A. Box A. Feurer I.D. Cavanaugh K.L. Understanding patient barriers to kidney transplant evaluation.Transplantation. 2015; 99: 1463-1469Crossref PubMed Scopus (30) Google Scholar Strategies for eliminating transplant access barriers have included shared accountability models; aligned quality metrics; standardized patient education; and external accountability of referrals, evaluations, and listings.2Patzer R.E. Pastan S.O. Policies to promote timely referral for kidney transplantation.Semin Dial. 2020; 33: 58-67Crossref PubMed Scopus (3) Google Scholar Regulatory and federal policies are also critical to address transplant access disparities. The changes to the KAS in 2014 sought to increase patient access to kidney transplantation. The Advancing American Kidney Health (AAKH) executive order issued July 2019 included a goal to improve kidney transplant access. Included in these reforms is the End Stage Renal Disease Treatment Choices (ETC) model. This model incentivizes dialysis facilities to reach 80% of patients with kidney failure on home dialysis or listed for transplant by 2025.13HHS.govHHS Launches President Trump’s ‘Advancing American Kidney Health’ Initiative.https://www.hhs.gov/about/news/2019/07/10/hhs-launches-president-trump-advancing-american-kidney-health-initiative.htmlGoogle Scholar To help achieve this, a new quality measure will be implemented in 2022, which will monitor the proportion of patients waitlisted at individual dialysis facilities.14Federal Register. Medicare Program; End-Stage Renal Disease Prospective Payment System, Payment for Renal Dialysis Services Furnished to Individuals With Acute Kidney Injury, End-Stage Renal Disease Quality Incentive Program, Durable Medical Equipment, Prosthetics, Orthotics and Supplies (DMEPOS) Competitive Bidding Program (CBP) and Fee Schedule Amounts, and Technical Amendments To Correct Existing Regulations Related to the CBP for Certain DMEPOS.https://www.federalregister.gov/documents/2018/11/14/2018-24238/medicare-program-end-stage-renal-disease-prospective-payment-system-payment-for-renal-dialysisGoogle Scholar While these policies provide a target and incentive for expansion of access to transplant, concrete mechanisms to achieve these goals are needed. The implementation of telemedicine in transplant prior to the COVID-19 pandemic has been slow. Evidence supports that posttransplant telemedicine improves self-monitoring and medication adherence in transplant recipients.15Forbes R.C. Broman K.K. Johnson T.B. et al.Implementation of telehealth is associated with improved timeliness to kidney transplant waitlist evaluation.J Telemed Telecare. 2018; 24: 485-491Crossref PubMed Scopus (12) Google Scholar Internet-based pretransplant education interventions for kidney failure patients include several programs—EXPLORE transplant, Health Options Patient Education, and iChoose Kidney tool. Telemedicine-based education improves monitoring and increases communication between patients and providers, while virtual care reduces costs, shortens time to evaluation and waitlist placement, and improves access to kidney transplantation.15Forbes R.C. Broman K.K. Johnson T.B. et al.Implementation of telehealth is associated with improved timeliness to kidney transplant waitlist evaluation.J Telemed Telecare. 2018; 24: 485-491Crossref PubMed Scopus (12) Google Scholar However, education level, income, race, and age are associated with disparities in digital access.16Roberts E.T. Mehrotra A. Assessment of disparities in digital access among Medicare beneficiaries and implications for telemedicine.JAMA Intern Med. 2020; 180: 1386-1389Crossref PubMed Scopus (67) Google Scholar Dialysis is a nearly universal alternative to transplant for patients in kidney failure, making dialysis centers an ideal safety net from which patients enter the kidney transplant pathway. Disparities exist from initial patient education, to referral, evaluation, listing, and ultimately transplantation itself and posttransplant care. Many inequities are concentrated in patient education, referrals, and failure to complete the evaluation process once referred to a transplant center. Telemedicine visits during hemodialysis are feasible, as they have been used by nephrologists to increase access to care.17Whitten P. Buis L. Use of telemedicine for haemodialysis: perceptions of patients and health-care providers, and clinical effects.J Telemed Telecare. 2008; 14: 75-78Crossref PubMed Scopus (22) Google Scholar A telemedicine collaboration between transplant centers and dialysis centers targeting these processes has the potential to improve disparities in kidney transplantation by bringing kidney transplant education and navigation to the dialysis chair, especially for patients in rural or underserved communities (Fig 1). Dialysis facilities are required to provide patient education on transplantation. However, there is a lack of standardized content and delivery, limited personnel resources at dialysis facilities, and unfamiliarity with individual transplant center eligibility requirements.2Patzer R.E. Pastan S.O. Policies to promote timely referral for kidney transplantation.Semin Dial. 2020; 33: 58-67Crossref PubMed Scopus (3) Google Scholar Direct partnership with a transplant center could allow dialysis patients to receive center-specific educational information delivered by transplant center staff. Dialysis facilities could also provide a convenient physical space to perform preliminary telemedicine-based education, screening, and assessment of potential living donors. Following education by the transplant team, a dialysis patient may express interest in a referral for transplantation. The convenience of transplant telemedicine in the dialysis center would allow patients to self-refer more frequently. This would reduce referral bias as a barrier for at-risk patients and increase equity overall, particularly in conjunction with standardized transplant education. Telemedicine infrastructure can allow for remote dialysis staff education and updates from transplant centers. These changes would reduce transplant staff travel burden, increasing the number of dialysis facilities and patients served. The use of telemedicine for preliminary transplant evaluation has shown to be effective at screening for eligible patients in a time- and cost-efficient fashion.15Forbes R.C. Broman K.K. Johnson T.B. et al.Implementation of telehealth is associated with improved timeliness to kidney transplant waitlist evaluation.J Telemed Telecare. 2018; 24: 485-491Crossref PubMed Scopus (12) Google Scholar At our center, efforts to adapt to COVID-19 required a multidisciplinary approach to perform initial transplant evaluations through electronic medical record portal or telephone visits. While an in-person assessment prior to kidney transplantation is needed, performing a virtual initial evaluation helps determine preliminary transplant candidacy. Patients can be assessed without traveling and can obtain blood work and other required diagnostic tests locally. The utilization of dialysis centers for virtual visits would help to eliminate disparities from loss to follow-up after referral or failure to complete the evaluation process. Notably, more than 25% of Medicare beneficiaries are without in-home broadband internet access or a smartphone with a wireless data plan, so community internet access through a local dialysis center becomes essential to avoid exacerbating access disparities through telemedicine evaluations.16Roberts E.T. Mehrotra A. Assessment of disparities in digital access among Medicare beneficiaries and implications for telemedicine.JAMA Intern Med. 2020; 180: 1386-1389Crossref PubMed Scopus (67) Google Scholar Overall, telemedicine could overcome many pre-existing barriers in access to kidney transplant, and facilitate longitudinal relationships between transplant centers and underserved communities. Dialysis facilities and transplant centers can build longitudinal relationships with one another and trust with patients through effective bidirectional communication spanning each stage of the transplant process. Dialysis center staff may mitigate barriers of technology literacy, shown to be associated with socioeconomic factors, by directly facilitating telemedicine visits using facility-owned tablet computers.18Mamedova S, Pawlowski E, Hudson L. A Description of US Adults Who Are Not Digitally Literate. Stats in Brief. US Department of Education, Washington DC (2018). Accessed June 30, 2020. https://nces.ed.gov/pubsearch/pubsinfo.asp?pubid=2018161Google Scholar The convenience of telemedicine would also allow for greater access to interpreter services, empowering patients with improved lines of communication with all providers. There are several limitations to effective implementation of a collaborative telemedicine approach to the kidney transplant process. Both dialysis and transplant centers must be intentional with adequate planning for telemedicine visits. Transplant centers and dialysis facilities must have sufficient personnel, and dialysis facilities need enhanced access to technology (videoconferencing devices and software, broadband internet) and physical infrastructure. To maintain privacy, headsets and privacy screens may be needed. Financial responsibility for implementation costs is another factor to consider, although policy changes such as the AAKH executive order and incentives from programs like the ETC model could help motivate these investments. Billing issues for simultaneous dialysis and transplant providers or reimbursement of telemedicine delivery across state lines will need to be resolved. While many patients have favored telemedicine over in-person visits during the COVID-19 pandemic, patient satisfaction with remote transplant visits during hemodialysis may vary.19Ramaswamy A. Yu M. Drangsholt S. et al.Patient satisfaction with telemedicine during the COVID-19 pandemic: retrospective cohort study.J Med Internet Res. 2020; 22e20786Crossref PubMed Scopus (63) Google Scholar Additionally, patients who undergo nocturnal in-center dialysis or peritoneal dialysis or who prefer at-home telemedicine visits would require alternative mechanisms to participate in the enhanced services. The AAKH executive order call to action has created urgency around increasing access to kidney transplantation. Telemedicine is at the forefront of health care delivery owing to COVID-19 and can be implemented to address these goals. Now is the time for stakeholders to work together and intentionally reduce disparities in kidney transplant access. This will require a multidisciplinary and multifacility approach to ensure no patient is left behind owing to their race, sex, education level, spoken language, socioeconomic status, or geographic location. A targeted telemedicine approach through collaboration between dialysis facilities and transplant centers may reduce transplant access barriers at the education, referral, and evaluation steps of the kidney transplant process.

OBJECTIVE: We describe a multilevel, collaborative research group for trainees and faculty engaging in transplant surgery research within one institution. DESIGN: Transplant Research, Education, and Engagement (TREE) was designed to develop trainees' research skills and foster enthusiasm in transplant surgery along the educational continuum. Our research model intentionally empowers junior researchers, including undergraduates and medical students, to assume active roles on a range of research projects and contribute new ideas within a welcoming research and learning environment. SETTING: Section of Transplant Surgery, Department of Surgery, Michigan Medicine, Ann Arbor, Michigan. PARTICIPANTS: Undergraduate premedical students, first through fourth year medical students, general surgery residents, transplant surgery fellows, and transplant surgery faculty. RESULTS: TREE was founded in September 2019 and has grown to include over 30 active members who meet weekly and collaborate virtually on a range of research projects, many of which are led by students. Trainees can assume both mentee and mentor roles and build their research, presentation and writing skills while collaborating academically. CONCLUSIONS: Our model has increased trainees' engagement in transplant research projects and fosters early enthusiasm for the field. This model can be feasibly replicated at other institutions and within other subspecialties. ((C) 2020 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

s technology and access to information evolve, so must our techniques in surgical education. The traditional surgical learning paradigm—consisting of textbook reading, didactics, simulation, and in-person operative instruction—is due for a modern supplement in line with advancing technology. Current surgical medical students and residents readily use digital platforms, with 2 institutional studies demonstrating that 90% of trainees use videos to prepare for cases. 1,2 Despite the widespread utilization of surgical videos for education, trainees often report that educational videos are poor quality or too long, suggesting that the current available learning content is discordant with the preferences of surgical trainees. Current videos also lack the ability for dynamic interaction and co-learning that can be integral to a meaningful learning experience. Contemporary social media, meanwhile, within which broadly utilizes social is time 3 considerable of surgical is tradi-tionally

Public Health Service increased risk donor kidneys are discarded 50% more often than nonincreased risk donor kidneys despite equivalent patient and graft survival outcomes. Patient and provider biases as well as challenges in risk interpretation contribute to the underuse of increased risk donor organs. As the ultimate decision to accept or reject an increased risk donor organ results from the patient-provider conversation, there is an opportunity to improve this dialogue. This report introduces the best-case/worst-case communication guide for structuring high-stake conversations on increased risk kidney offers between transplant providers and their patients. Through best case/worst case, providers focus on eliciting patient values and long-term goals. The patient's unique context can then inform an individualized discussion of "best," "worst," and "most likely" outcomes and support the provider's ultimate recommendation. Transplant providers are encouraged to adopt this communication strategy to enhance shared decision-making and improve patient outcomes.

Amyotrophic lateral sclerosis (ALS) is a lethal and incurable neurodegenerative disorder commonly associated with repeat expansion in the C9orf72 gene; termed C9-ALS. A major pathological feature of this is the accumulation of arginine-rich (R-rich) dipeptide repeat (DPR) polypeptides in neurons. R-rich DPRs interact with low complexity domains in proteins, accumulate in membraneless organelles (MLOs), alter the material properties of MLOs, and induce cell death. The molecular mechanisms underlying pathogenesis, though, remain unknown. R-rich DPRs infiltrate nucleoli, co-localize with nucleophosmin (NPM1), and alter NPM1 phase separation in vitro. NPM1 is crucial to the maintenance of nucleolar liquid-like properties through its ability to phase separate with proteins and nucleic acids. Elucidating the effects of DPR interactions with NPM1 on the liquid-like properties and overall architecture of nucleoli that ultimately lead to nucleolar dysfunction and cell death is critical to understanding C9-ALS. Here we employ poly(PR) as an archetypal R-rich DPR to (1) identify the interactions mediating phase separation with NPM1; (2) elucidate the mechanisms causing the DPR-dependent dissolution of in vitro NPM1/DPR droplets; and (3) confirm hypotheses stimulated by our biophysical results regarding the mechanisms of DPR-mediated nucleolar disruption in cells. Results from multiple, complementary biochemical and biophysical techniques show that (1) NPM1/DPR interactions are mediated by acidic tracts within the intrinsically disorder region of NPM1, (2) R-rich DPRs dissolve NPM1-containing droplets in vitro by sequestering NPM1 into large saturated complexes, and (3) exogenous poly(PR) induces NPM1 release from nucleoli, disrupting nucleolar organization and function. These results support the hypothesis that R-rich DPRs, mediate their toxic effects in part through saturation/sequestration of NPM1, perturbing NPM1 mediated phase separation in nucleoli, disrupting nucleolar function, and inducing cell death.

Repeat expansion in the C9orf72 gene is the most common cause of the neurodegenerative disorder amyotrophic lateral sclerosis (C9-ALS) and is linked to the unconventional translation of five dipeptide-repeat polypeptides (DPRs). The two enriched in arginine, poly(GR) and poly(PR), infiltrate liquid-like nucleoli, co-localize with the nucleolar protein nucleophosmin (NPM1), and alter the phase separation behavior of NPM1 in vitro. Here, we show that poly(PR) DPRs bind tightly to a long acidic tract within the intrinsically disordered region of NPM1, altering its phase separation with nucleolar partners to the extreme of forming large, soluble complexes that cause droplet dissolution in vitro. In cells, poly(PR) DPRs disperse NPM1 from nucleoli and entrap rRNA in static condensates in a DPR-length-dependent manner. We propose that R-rich DPR toxicity involves disrupting the role of phase separation by NPM1 in organizing ribosomal proteins and RNAs within the nucleolus.