Ethics of Resident Involvement in Surgical Training.

AbstractBackground: Attending surgeons must maintain balance between promoting education and assuring safe, transparent patient care. This investigation aimed to define ethics that guide surgical training. We hypothesized that resident autonomy in the operating room is influenced by attending approach to patients, specifically patients considered to be vulnerable. MATERIALS AND METHODS: After IRB approval, surgeons from three institutions were invited to participate in a pilot, survey, exploring how principles of patient autonomy, physician beneficence, nonmaleficence, and justice apply to participant opinions. Responses were transcribed and coded for quantitative and qualitative analysis. RESULTS: 51 attendings and 55 residents completed the survey. We identified that patient autonomy is upheld through transparent consent practices. Intraoperative supervision is a key practice that maintains the principles of physician beneficence and nonmaleficence and mitigates the risk of resident participation. Vulnerable patients were defined by respondents as those unable to participate in their own consent and those limited by social determinants of health and barriers to medical literacy. In contrast, resident participation is not limited in the care of vulnerable patients but is restricted in cases of higher complexity and those procedures deemed to have lower error margins. CONCLUSIONS: Although residents measure the success of their training based on their level of intraoperative independence, autonomy afforded to the resident does not only depend on objective skill. There are ethical considerations that the attending must navigate as they decide on effective teaching and safe surgical management, which is especially relevant in the care of complex cases.

MINIMALLY INVASIVE SURGICAL REPAIR FOR ABDOMINAL WALL HERNIAS IN NONHUMAN PRIMATES, TWO CASES IN WESTERN LOWLAND GORILLAS (GORILLA GORILLA GORILLA).

A 33-yr-old female Western lowland gorilla (Gorilla gorilla gorilla) was diagnosed with a congenital umbilical hernia that was reducible and asymptomatic; change in the hernia was noted after parturition and concerns regarding increased risk of bowel incarceration developed. The hernia was successfully repaired with robot-assisted laparoscopic surgery. A 5-mon-old male Western lowland gorilla presented with bilateral inguinal hernias that were repaired via elective laparoscopic repair. In both cases, the gorillas did well without complications and never appeared to acknowledge wounds or exhibit signs of pain postoperatively. A literature review and interinstitutional survey was conducted to determine success rate of minimally invasive versus open repair of hernias in nonhuman primates (NHP). Of the cases identified, recurrence and/or wound morbidity was seen in 0% of laparoscopic repairs and 50% of open repairs. NHP may benefit from elective, minimally invasive surgical techniques that may reduce hernia recurrences and wound morbidity.

High K+ intake alleviates experimental autoimmune encephalomyelitis (EAE) and increases T regulatory cells.

Multiple sclerosis is believed to be triggered by the interplay between the environmental and genetic factors. In contrast to the Paleolithic diet, the modern Western diet is high in Na+ and low in K+. The present study was undertaken to determine whether high K+ intake alleviated experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. Treatment of C57BL/6 or SJL mice for 7 days with a 5 % K+ diet prior to induction of EAE and maintaining mice on the diet until the end of experiments delayed the onset, reduced the peak, and accelerated the recovery of EAE in both strains compared with mice on a control diet (0.7 % K+), whereas feeding C57BL/6 mice with a 0.1 % K+ diet did the opposite. High K+ intake increased the splenic Treg cell frequency in the pretreatment and peak EAE. Thus, high K+ intake attenuates EAE, possibly by increasing the Treg cells.

NFAT5 contributes to the pathogenesis of experimental autoimmune encephalomyelitis (EAE) and decrease of T regulatory cells in female mice.

Multiple sclerosis disproportionally affects women. The present study was undertaken to determine whether NFAT5 contributed to the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, and if it did, whether the impact was sex associated. NFAT5 haplodeficiency reduced the disease severity only in female mice. This effect was associated with significant increases in frequency of T regulatory (Treg) cells in the CNS (from 1.45 ± 0.39% to 3.73 ± 0.94%) and spleen from (0.31 ± 0.06% to 0.94 ± 0.29%) without significantly affecting the CNS CD4+ subsets frequency. NFAT5 haploinsufficiency also significantly reduced the frequency of CD11c+CD8α+ dendritic cells in the female CNS. However, increase of their frequency in the CNS via intraperitoneal Flt3L injection at peak EAE had no significant effect on the disease courses. We conclude that NFAT5 contributes to pathogenesis of EAE in female mice, possibly through decreasing tissue specific frequency of Treg cells.

A Multicenter Analysis of the Early Impact of COVID-19 on Junior Resident Operative Case Volume.

INTRODUCTION: Institutions have reported decreases in operative volume due to COVID-19. Junior residents have fewer opportunities for operative experience and COVID-19 further jeopardizes their operative exposure. This study quantifies the impact of the COVID-19 pandemic on resident operative exposure using resident case logs focusing on junior residents and categorizes the response of surgical residency programs to the COVID-19 pandemic. MATERIALS AND METHODS: A retrospective multicenter cohort study was conducted; 276,481 case logs were collected from 407 general surgery residents of 18 participating institutions, spanning 2016-2020. Characteristics of each institution and program changes in response to COVID-19 were collected via surveys. RESULTS: Senior residents performed 117 more cases than junior residents each year (P < 0.001). Prior to the pandemic, senior resident case volume increased each year (38 per year, 95% confidence interval 2.9-74.9) while junior resident case volume remained stagnant (95% confidence interval 13.7-22.0). Early in the COVID-19 pandemic, junior residents reported on average 11% fewer cases when compared to the three prior academic years (P = 0.001). The largest decreases in cases were those with higher resident autonomy (Surgeon Jr, P = 0.03). The greatest impact of COVID-19 on junior resident case volume was in community-based medical centers (246 prepandemic versus 216 during pandemic, P = 0.009) and institutions which reached Stage 3 Program Pandemic Status (P = 0.01). CONCLUSIONS: Residents reported a significant decrease in operative volume during the 2019 academic year, disproportionately impacting junior residents. The long-term consequences of COVID-19 on junior surgical trainee competence and ability to reach cases requirements are yet unknown but are unlikely to be negligible.

CD8+ T cells: The past and future of immune regulation.

Regulation of the adaptive immune response is critical for health. Regulatory activity can be found in multiple components of the immune system, however, the focus on particular components of the immune regulatory network has left many aspects of this critical immune component understudied. Here we review the evidence for activities of CD8+ T cells in immune homeostasis and regulation of autoimmune reactivity. The heterogeneous nature of identified CD8+ cell types are examined, and common phenotypes associated with functional activities are defined. The varying types of antigen signal crucial for CD8+ T cell regulatory activity are identified and the implications of these activation pathways for control of adaptive responses is considered. Finally, the promising capacity for transgenic antigen receptor directed cytotoxicity as a mechanism for modulation of autoimmunity is detailed.

A novel CNS-homing peptide for targeting neuroinflammatory lesions in experimental autoimmune encephalomyelitis.

Using phage peptide library screening, we identified peptide-encoding phages that selectively home to the inflamed central nervous system (CNS) of mice with experimental autoimmune encephalomyelitis (EAE), a model of human multiple sclerosis (MS). A phage peptide display library encoding cyclic 9-amino-acid random peptides was first screened ex-vivo for binding to the CNS tissue of EAE mice, followed by in vivo screening in the diseased mice. Phage insert sequences that were present at a higher frequency in the CNS of EAE mice than in the normal (control) mice were identified by DNA sequencing. One of the phages selected in this manner, denoted as MS-1, was shown to selectively recognize CNS tissue in EAE mice. Individually cloned phages with this insert preferentially homed to EAE CNS after an intravenous injection. Similarly, systemically-administered fluorescence-labeled synthetic MS-1 peptide showed selective accumulation in the spinal cord of EAE mice. We suggest that peptide MS-1 might be useful for targeted drug delivery to CNS in EAE/MS.

Targeting antigen presentation in autoimmunity.

Autoimmune diseases are heterogeneous group of disorders that together represent an enormous societal and medical problem. CD4+ T cells have critical roles in the initiation and pathogenesis of autoimmune disease. As such, modulation of T cell activity has proven to have significant therapeutic effects in multiple autoimmune settings. T cell activation is a complex process with multiple potential therapeutic targets, many of which have been successfully utilized to treat human disease. Current pharmacological treatment largely targets T cell intrinsic activities as a means of treating various autoimmune disorders. Here I review extant and potential therapeutic approaches that instead specifically target antigen presentation to CD4+ T cells as a critical checkpoint in autoimmune responses. In addition, the contribution of antigen modulation components in current therapeutic approaches is considered along with the impact of new antigen targeted treatment modalities. Finally, potential challenges are considered in the context of the potential for antigen specific targeting of the antigen presentation process.

RGC-32 Promotes Th17 Cell Differentiation and Enhances Experimental Autoimmune Encephalomyelitis.

Th17 cells play a critical role in autoimmune diseases, including multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. Response gene to complement (RGC)-32 is a cell cycle regulator and a downstream target of TGF-ß that mediates its profibrotic activity. In this study, we report that RGC-32 is preferentially upregulated during Th17 cell differentiation. RGC-32-/- mice have normal Th1, Th2, and regulatory T cell differentiation but show defective Th17 differentiation in vitro. The impaired Th17 differentiation is associated with defects in IFN regulatory factor 4, B cell-activating transcription factor, retinoic acid-related orphan receptor γt, and SMAD2 activation. In vivo, RGC-32-/- mice display an attenuated experimental autoimmune encephalomyelitis phenotype accompanied by decreased CNS inflammation and reduced frequency of IL-17- and GM-CSF-producing CD4+ T cells. Collectively, our results identify RGC-32 as a novel regulator of Th17 cell differentiation in vitro and in vivo and suggest that RGC-32 is a potential therapeutic target in multiple sclerosis and other Th17-mediated autoimmune diseases.

Engineered MBP-specific human Tregs ameliorate MOG-induced EAE through IL-2-triggered inhibition of effector T cells.

Expanded polyclonal T regulatory cells (Tregs) offer great promise for the treatment of immune-mediated diseases. Inhibition by Tregs is under the control of the T-cell receptor (TCR). Therefore, we created Tregs with defined antigen specificity, using a recombinant T-cell receptor isolated from a myelin-basic protein specific T-cell clone of a multiple sclerosis (MS) patient (Ob2F3). We expressed this TCR using a retroviral expression vector in human Tregs from peripheral blood. We observed that transduced Tregs were activated in vitro in response to myelin basic protein (MBP) peptide on DR15 antigen-presenting cells (APC) and upregulated Treg markers, Foxp3, LAP and Helios. These engineered MBP-specific Tregs could suppress MBP-specific T effector cells, and were also able to suppress T cells with other specificities after Tregs had been activated through the TCR. Importantly, we showed that these engineered Tregs were able to function effectively in the presence of strong TLR-induced inflammatory signals, and that MBP-specific Tregs ameliorated EAE in myelin oligodendrocyte glycoprotein (MOG)-immunized DR15 transgenic mice. We further demonstrated in vitro that IL-2 produced by neighboring effector T cells activated MBP-specific Tregs, initiating contact-independent suppression to T effectors in local milieu. Mechanistic studies demonstrated that bystander suppression in vivo may involve transfer of soluble mediators, enhanced by cell contact between Tregs and effectors. Taken together, we show that engineered clonal MBP-specific Tregs are able to suppress autoimmune pathology in EAE. This approach may serve as a cellular therapy for MS patients with the common DR15 haplotype that is associated with disease susceptibility.

Progression of experimental autoimmune encephalomyelitis is associated with up-regulation of major sodium transporters in the mouse kidney cortex under a normal salt diet.

Recent demonstrations of exacerbation of experimental autoimmune encephalomyelitis (EAE) by high salt diets prompted us to study whether EAE stimulated Na absorption by the renal cortex, a primary regulatory site for Na balance, even under a normal NaCl diet. We found that as EAE progressed from mild to severe symptoms, there were parallel increases in the protein abundance of NHE3 and αENaC and the Na,K-ATPase activity with an affiliated elevation of its ß1-subunit protein. These effects are associated with increases in the protein levels of the well-known regulators SGK1 and scaffold NHERF2, and phosphorylation of ERK1/2. These effects of EAE could not be explained by reduction in water or food intake. We conclude that EAE progression is associated with up-regulation of major Na transporters, which is most likely driven by increased expression of SGK1 and NHERF2 and activation of ERK1/2. These data suggest that EAE progression increases Na absorption by the renal cortex.

Interferon gamma in autoimmunity: A complicated player on a complex stage.

Early views of autoimmune disease cast IFNγ as a prototypic pro-inflammatory factor. It is now clear that IFNγ is capable of both pro- and anti-inflammatory activities with the functional outcome dependent on the physiological and pathological setting examined. Here, the major immune modulatory activities of IFNγ are reviewed and current evidence for the impact of IFNγ on pathology and regulation of several autoimmune diseases and disease models is summarized.

Pre-existing central nervous system lesions negate cytokine requirements for regional experimental autoimmune encephalomyelitis development.

In region-specific forms of experimental autoimmune encephalomyelitis (EAE), lesion initiation is regulated by T-cell-produced interferon-γ (IFN-γ) resulting in spinal cord disease in the presence of IFN-γ and cerebellar disease in the absence of IFN-γ. Although this role for IFN-γ in regional disease initiation is well defined, little is known about the consequences of previous tissue inflammation on subsequent regional disease, information vital to the development of therapeutics in established disease states. This study addressed the hypothesis that previous establishment of regional EAE would determine subsequent tissue localization of new T-cell invasion and associated symptoms regardless of the presence or absence of IFN-γ production. Serial transfer of optimal or suboptimal doses of encephalitogenic IFN-γ-sufficient or -deficient T-cell lines was used to examine the development of new clinical responses associated with the spinal cord and cerebellum at various times after EAE initiation. Previous inflammation within either cerebellum or spinal cord allowed subsequent T-cell driven inflammation within that tissue regardless of IFN-γ presence. Further, T-cell IFN-γ production after initial lesion formation exacerbated disease within the cerebellum, suggesting that IFN-γ plays different roles at different stages of cerebellar disease. For the spinal cord, IFN-γ-deficient cells (that are ordinarily cerebellum disease initiators) were capable of driving new spinal-cord-associated clinical symptoms more than 60 days after the initial acute EAE resolution. These data suggest that previous inflammation modulates the molecular requirements for new neuroinflammation development.

Variations in procedure time based on surgery resident postgraduate year level.

BACKGROUND: With increasing scrutiny being placed on the allocation of health care dollars, data supporting the increased resources used to teach residents in the operating room (OR) are lacking. METHODS: All cases of patients undergoing laparoscopic cholecystectomies (LCs) and pancreaticoduodenectomies (PDs) from July 1, 2006 to July 1, 2011 were analyzed. Procedures were excluded based on the following: more than one resident listed in the operative report, with the exception of interns; LC requiring cholangiogram or conversion to an open procedure; or if a PD required additional procedures. Multiple linear regression was used to evaluate the association between procedure time and postgraduate year (PGY), adjusting for patient age and estimated blood loss. RESULTS: A total of 236 PDs and 357 LCs were included in the study. For LCs, after multiple linear regression, the association between procedure time and resident PGY was marginally significant (P = 0.0519) and suggested an inverse relationship; for every increase in resident PGY, there was a 2.66-min decrease in OR time. Based on our institution's figure of $18.13/min of OR time, the cost difference between PGYs 1 and 5 performing a LC would be $192.90 per case. For PDs, however, the association between procedure time and resident PGY was not significant. CONCLUSIONS: Junior residents likely prolong procedure times for more basic procedures such as LC but not for more complex procedures such as PD.

Establishing a swine model to compare vascular prostheses in a contaminated field.

OBJECTIVE: Patch arteriotomies are performed during many vascular procedures. Whereas synthetic materials are generally felt to be inappropriate for infected environments, the suitability of glutaraldehyde-treated bovine pericardium (GBP), a biologic material, in such instances is unknown. Our main objectives were to develop an animal model to study vascular prostheses while comparing the infectability of polyester (Dacron) and GBP in a topically infected environment. METHODS: Twenty-three pigs underwent transabdominal patch arteriotomy of the infrarenal aorta with either Dacron or GBP. The patches were inoculated with sterile saline (1 per group), Staphylococcus aureus 10(4) colony-forming units (CFUs) (4 per group), or S. aureus 10(5) CFUs (6 per group). At 3 wk, the animals were euthanized, and the patches were removed via a left retroperitoneal approach. Specimens were collected for microbiologic and histologic analysis. RESULTS: One animal from each group inoculated with 10(5) CFUs died during the study period, and another died immediately postoperatively of an airway complication. All aortas were patent and without evidence of pseudoaneurysm formation. Gross abscesses were found in 4/6 Dacron and 5/6 GBP animals receiving 10(5) CFUs. Similarly, 4/6 animals implanted with Dacron and 5/6 animals implanted with GBP had positive tissue cultures. A histologic grading system of inflammation substantiated the culture results. CONCLUSIONS: No significant difference exists between Dacron and GBP to resist bacterial infection at 3 wk. We have established a reproducible in vivo model to study arterial patch materials in a topically infected environment.

Anecdotes Drive Attitudes, Data Drives Decisions: Optimizing the Emergency Department Workup Prior to Surgical Consultations.

PURPOSE: Emergency department (ED) wait times and ED length of stay (LOS) have a significant impact on patient morbidity and mortality and patient satisfaction. Consultation-to-decision time can contribute to increased wait times and LOS in the ED. Up to 40% of patients presenting to the ED require consultation from subspecialty services. We hypothesize that in surgical patients, completion of workup prior to consultation will decrease consultation-to-decision time, ED wait times, and LOS in the ED. METHODS: A retrospective review was conducted at a single site including all overnight general surgery consultations from the ED over 2-months. Data collected included wait times, LOS, and workup completed prior to consultation. Summary statistics were calculated and bivariate tests were performed using t-tests for continuous variables. RESULTS: Time to final surgical plan and LOS in ED were evaluated for 137 patients comparing "complete" and "incomplete" workups at time of consultation. It was considered a "complete" workup if labs and imaging were resulted prior to time of consult. If any baseline tests were not ordered prior to time of consult, it was considered an "incomplete" workup. Analysis demonstrated an average time of 4.9 and 2.5 hours for consultation-to-decision time for "incomplete" and "complete" workups respectively (p < 0.0001). For LOS in ED, there was an average of 11.4 and 7.9 hours for "incomplete" and "complete" workups respectively (p < 0.0001). CONCLUSIONS: There is a significant difference in consultation-to-decision time and LOS in the ED when consultation is performed following a complete versus incomplete workup for surgical patients independent of inherent wait times for testing to result and the need for additional testing requested from consulting services. Developing strategies to optimize workups from the ED prior to surgical consultation, including the development of care pathways, could significantly decrease patient wait times and LOS in the ED.

Outcomes of the 2021-2022 APDS General Surgery Recruitment Process Recommendations.

BACKGROUND: In recent years, mounting challenges for applicants and programs in resident recruitment have catapulted this topic into a top priority in medical education. These challenges span all aspects of recruitment-from the time an applicant applies until the time of the Match-and have widespread implications on cost, applicant stress, compromise of value alignment, and holistic review, and equity. In 2021-2022, the Association of Program Directors in Surgery (APDS) set forth recommendations to guide processes for General Surgery residency recruitment. OBJECTIVES: This work summarizes the APDS 2021-2022 resident recruitment process recommendations, along with their justification and program end-of-cycle program feedback and compliance. This work also outlines the impact of these data on the subsequent 2022-2023 recommendations. METHODS: After a comprehensive review of the available literature and data about resident recruitment, the APDS Task Force proposed recommendations to guide 2021-2022 General Surgery resident recruitment. Following cycle completion, programs participating in the categorical General Surgery Match were surveyed for feedback and compliance. RESULTS: About 122 of the 342 programs (35.7%) participating in the 2022 categorical General Surgery Match responded. Based on available data in advance of the cycle, recommendations around firm application and interview numbers could not be made. About 62% of programs participated in the first round interview offer period with 86% of programs limiting offers to the number of slots available; 95% conducted virtual-only interviews. Programs responded they would consider or strongly consider the following components in future cycles: holistic review (90%), transparency around firm requirements (88%), de-emphasis of standardized test scores (54%), participation in the ERAS Supplemental application (58%), single first round interview release period (69%), interview offers limited to the number of available slots (93%), 48-hour minimum interview offer response time (98%), operationalization of applicant expectations (88%), and virtual interviews (80%). There was variability in terms of the feedback regarding the timing of the single first round offer period as well as support for a voluntary, live site visit for applicants following program rank list certification. CONCLUSIONS: The majority of programs would consider implementing similar recommendations in 2022-2023. The greatest variability around compliance revolved around single interview release and the format of interviews. Future innovation is contingent upon the ongoing collection of data as well as unification of data sources involved in the recruitment process.

Prolonged antigen presentation is required for optimal CD8+ T cell responses against malaria liver stage parasites.

Immunization with irradiated sporozoites is currently the most effective vaccination strategy against liver stages of malaria parasites, yet the mechanisms underpinning the success of this approach are unknown. Here we show that the complete development of protective CD8+ T cell responses requires prolonged antigen presentation. Using TCR transgenic cells specific for the malaria circumsporozoite protein, a leading vaccine candidate, we found that sporozoite antigen persists for over 8 weeks after immunization--a remarkable finding since irradiated sporozoites are incapable of replication and do not differentiate beyond early liver stages. Persisting antigen was detected in lymphoid organs and depends on the presence of CD11c+ cells. Prolonged antigen presentation enhanced the magnitude of the CD8+ T cell response in a number of ways. Firstly, reducing the time primed CD8+ T cells were exposed to antigen in vivo severely reduced the final size of the developing memory population. Secondly, fully developed memory cells expanded in previously immunized mice but not when transferred to naïve animals. Finally, persisting antigen was able to prime naïve cells, including recent thymic emigrants, to become functional effector cells capable of eliminating parasites in the liver. Together these data show that the optimal development of protective CD8+ T cell immunity against malaria liver stages is dependent upon the prolonged presentation of sporozoite-derived antigen.

IL-1R signaling within the central nervous system regulates CXCL12 expression at the blood-brain barrier and disease severity during experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is an autoimmune disease of the CNS characterized by disruption of the blood-brain barrier (BBB). This breach in CNS immune privilege allows undeterred trafficking of myelin-specific lymphocytes into the CNS where they induce demyelination. Although the mechanism of BBB compromise is not known, the chemokine CXCL12 has been implicated as a molecular component of the BBB whose pattern of expression is specifically altered during MS and which correlates with disease severity. The inflammatory cytokine IL-1beta has recently been shown to contribute not only to BBB permeability but also to the development of IL-17-driven autoimmune responses. Using experimental autoimmune encephalomyelitis, the rodent model of MS, we demonstrate that IL-1beta mediates pathologic relocation of CXCL12 during the induction phase of the disease, before the development of BBB disruption. We also show that CD4, CD8, and, surprisingly gammadelta T cells are all sources of IL-1beta. In addition, gammadelta T cells are also targets of this cytokine, contributing to IL-1beta-mediated production of IL-17. Finally, we show that the level of CNS IL-1R determines the clinical severity of experimental autoimmune encephalomyelitis. These data suggest that T cell-derived IL-1beta contributes to loss of immune privilege during CNS autoimmunity via pathologic alteration in the expression of CXCL12 at the BBB.

Integration of Educational Technology.

Continued advancement has forced medical education to accept new ways in which to incorporate technology into its curriculum. As a result, technology has become a cornerstone to all levels of the medical education. This article compiles and discusses various avenues in which technology serves and betters education, ranging from administrative databases to cloud-based storage. Overall, technology can serve various educational purposes, including compilation, circulation, and integration of educational materials. The modalities discussed within this article, while numerous and adaptable, are a small portion of what the technological world has to offer.