Surgical Regret and Intraoperative Decision-Making: A Living Donor Kidney Case.

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.

Variability in surgical approaches to hernias in patients with ascites.

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.

Intra-axonal translation of Khsrp mRNA slows axon regeneration by destabilizing localized mRNAs.

Axonally synthesized proteins support nerve regeneration through retrograde signaling and local growth mechanisms. RNA binding proteins (RBP) are needed for this and other aspects of post-transcriptional regulation of neuronal mRNAs, but only a limited number of axonal RBPs are known. We used targeted proteomics to profile RBPs in peripheral nerve axons. We detected 76 proteins with reported RNA binding activity in axoplasm, and levels of several change with axon injury and regeneration. RBPs with altered levels include KHSRP that decreases neurite outgrowth in developing CNS neurons. Axonal KHSRP levels rapidly increase after injury remaining elevated up to 28 days post axotomy. Khsrp mRNA localizes into axons and the rapid increase in axonal KHSRP is through local translation of Khsrp mRNA in axons. KHSRP can bind to mRNAs with 3'UTR AU-rich elements and targets those transcripts to the cytoplasmic exosome for degradation. KHSRP knockout mice show increased axonal levels of KHSRP target mRNAs, Gap43, Snap25, and Fubp1, following sciatic nerve injury and these mice show accelerated nerve regeneration in vivo. Together, our data indicate that axonal translation of the RNA binding protein Khsrp mRNA following nerve injury serves to promote decay of other axonal mRNAs and slow axon regeneration.

Fostering Passion and Skills in Surgical Research Across the Medical Education Continuum: The Transplant Research, Education, and Engagement Group.

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.

Introduction to the Best-Case/Worst-Case Framework Within Transplantation Surgery to Improve Decision-Making for Increased Risk Donor Organ Offers.

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.

C9orf72 Poly(PR) Dipeptide Repeats Disturb Biomolecular Phase Separation and Disrupt Nucleolar Function.

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.