A noradrenergic-hypothalamic neural substrate for stress-induced sleep disturbances.

In our daily life, we are exposed to uncontrollable and stressful events that disrupt our sleep. However, the underlying neural mechanisms deteriorating the quality of non-rapid eye movement sleep (NREMs) and REM sleep are largely unknown. Here, we show in mice that acute psychosocial stress disrupts sleep by increasing brief arousals (microarousals [MAs]), reducing sleep spindles, and impairing infraslow oscillations in the spindle band of the electroencephalogram during NREMs, while reducing REMs. This poor sleep quality was reflected in an increased number of calcium transients in the activity of noradrenergic (NE) neurons in the locus coeruleus (LC) during NREMs. Opto- and chemogenetic LC-NE activation in naïve mice is sufficient to change the sleep microarchitecture similar to stress. Conversely, chemogenetically inhibiting LC-NE neurons reduced MAs during NREMs and normalized their number after stress. Specifically inhibiting LC-NE neurons projecting to the preoptic area of the hypothalamus (POA) decreased MAs and enhanced spindles and REMs after stress. Optrode recordings revealed that stimulating LC-NE fibers in the POA indeed suppressed the spiking activity of POA neurons that are activated during sleep spindles and REMs and inactivated during MAs. Our findings reveal that changes in the dynamics of the stress-regulatory LC-NE neurons during sleep negatively affect sleep quality, partially through their interaction with the POA.

Lung Transplantation After Ex Vivo Lung Perfusion Early Outcomes From a US National Registry.

OBJECTIVE: The objective of this study was to examine early lung transplant outcomes following EVLP using a large national transplant registry. SUMMARY OF BACKGROUND DATA: Lung transplantation in the United States continues to be constrained by a limited supply of donor organs. EVLP has the potential to significantly increase the available pool of donor lung allografts through the reconditioning of "marginal" organs. METHODS: The united network for organ sharing registry was queried for all adults (age ≥18) who underwent first-time lung transplantation between March 2018 (when united network for organ sharing began collecting confirmed donor EVLP status) and June 2019. Transplants were stratified by EVLP use. The primary outcome was short-term survival and secondary outcomes included acute rejection before discharge and need for extracorpo-real membrane oxygenation support post-transplant. RESULTS: A total of 3334 recipients met inclusion criteria including 155 (5%) and 3179 (95%) who did and did not receive allografts that had undergone EVLP, respectively. On unadjusted descriptive analysis, EVLP and non-EVLP cohorts had similar 180-day survival (92% vs 92%, P = 0.9). EVLP use was associated with a similar rate of acute rejection (13% vs 9%, P = 0.08) but increased rate of early extracorporeal membrane oxygenation use (12% vs 7%, P = 0.04). After adjustment, EVLP use was not associated with significantly increased mortality (adjusted hazard ratio 0.99, 95% confidence interval 0.62-1.58) or acute rejection (adjusted odds ratio 0.89, 95% confidence interval 0.40-1.97) compared to non-EVLP use. CONCLUSIONS: In the largest national series of EVLP lung transplant recipients, EVLP is associated with early recipient outcomes comparable to that of non-EVLP recipients with similar baseline characteristics. Longer term follow-up data is needed to further assess the impact of EVLP on post-lung transplant outcomes.

First porcine to human kidney transplantation performed in the United States.

In an operation that lasted a little over 2 h, surgeons at New York University Langone Health transplanted a porcine kidney into a human patient without signs of early rejection. This is a landmark achievement for xenotransplantation, a field that has been revived in the past decade and promises a new avenue to address critical organ shortage worldwide.

Preoperative carfilzomib and lulizumab based desensitization prolongs graft survival in a sensitized non-human primate model.

Sensitized patients are difficult to transplant due to pre-formed anti-donor immunity. We have previously reported successful desensitization using carfilzomib and belatacept in a non-human primate (NHP) model. Here we evaluated selective blockade of the co-stimulatory signal (CD28-B7) with Lulizumab, which preserves the co-inhibitory signal (CTLA4-B7). Five maximally MHC-mismatched pairs of NHPs were sensitized to each other with two sequential skin transplants. Individuals from each pair were randomized to either desensitization with once-weekly Carfilzomib (27mg/m2 IV) and Lulizumab (12.5mg/kg SC) over four weeks, or no desensitization (Control). NHPs then underwent life-sustaining kidney transplantation from their previous skin donor. Rhesus-specific anti-thymocyte globulin was used as induction therapy and immunosuppression maintained with tacrolimus, mycophenolate, and methylprednisolone. Desensitized subjects demonstrated a significant reduction in donor-specific antibody, follicular helper T cells (CD4+PD-1+ICOS+), and proliferating B cells (CD20+Ki67+) in the lymph nodes. Interestingly, regulatory T cell (CD4+CD25+CD127lo) frequency was maintained after desensitization in addition to increased frequency of naïve CD4 T cells (CCR7+CD45RA+) and naïve B cells (IgD+CD27-CD20+) in circulation. This was associated with significant prolongation in graft survival (MST = 5.8 ± 4.0 vs. 64.8 ± 36.3; p<0.05) and lower antibody-mediated rejection scores compared to control animals. However, all desensitized animals eventually developed AMR and graft failure. Desensitization with CFZ and Lulizumab improves allograft survival in allosensitized NHPs, by transient control of the germinal center and shifting of the immune system to a more naive phenotype. This regimen may translate into clinical practice to improve outcomes of highly sensitized transplant patients.

Sex differences in gene expression in response to ischemia in the human left ventricular myocardium.

Sex differences exist in the prevalence, presentation and outcomes of ischemic heart disease (IHD). Females have higher risk of heart failure post-myocardial infarction relative to males and are two to three times more likely to die after coronary artery bypass grafting surgery. We examined sex differences in human myocardial gene expression in response to ischemia. Left ventricular biopsies from 68 male/46 female patients undergoing aortic valve replacement surgery were obtained at baseline and after a median 74 min of cold cardioplegic arrest/ischemia. Transcriptomes were quantified by RNA-sequencing. Cell-type enrichment analysis was used to estimate the identity and relative proportions of different cell types in each sample. A sex-specific response to ischemia was observed for 271 genes. Notably, the expression FAM5C, PLA2G4E and CYP1A1 showed an increased expression in females compared to males due to ischemia and DIO3, MT1G and CMA1 showed a decreased expression in females compared to males due to ischemia. Functional annotation analysis revealed sex-specific modulation of the oxytocin signaling pathway and common pathway of fibrin clot formation. Expression quantitative trait locus (eQTL) analysis identified variant-by-sex interaction eQTLs, indicative of sex differences in the genotypic effects on gene expression. Cell-type enrichment analysis showed sex-bias in proportion of specific cell types. Common lymphoid progenitor cells and M2 macrophages were found to increase in female samples from pre- to post-ischemia, but no change was observed in male samples. These differences in response to myocardial ischemia provide insight into the sexual dimorphism of IHD and may aid in the development of sex-specific therapies that reduce myocardial injury.

A three-tier system for evaluation of organ procurement organizations' willingness to pursue and utilize nonideal donor lungs.

Lungs from "nonideal," but acceptable donors are underutilized; however, organ procurement organization (OPO) metrics do not reflect the extent to which OPO-specific practices contribute to these trends. We developed a comprehensive system to evaluate nonideal lung donor avoidance, or risk aversion among OPOs. Adult donors in the UNOS registry who donated ≥1 organ for transplantation between 2007 and 2018 were included. Nonideal donors had any of age>50, smoking history ≥20 pack-years, PaO2 /FiO2 ratio ≤350, donation after circulatory death, or increased risk status. OPO-level risk aversion in donor pursuit, consent attainment, lung recovery, and transplantation was assessed. Among 83916 donors, 70372 (83.9%) were nonideal. Unadjusted OPO-level rates of nonideal donor pursuit ranged from 81 to 100%. In a three-tier system of overall risk aversion, tier 3 OPOs (least risk-averse) had the highest rates of nonideal donor pursuit, consent attainment, lung recovery, and transplantation. Tier 1 OPOs (most risk-averse) had the lowest rates of donor pursuit, consent attainment, and lung recovery, but higher rates of transplantation compared to tier 2 OPOs (moderately risk-averse). Risk aversion varies among OPOs and across the donation process. OPO evaluations should reflect early donation process stages to best differentiate over- and underperforming OPOs and encourage optimal OPO-specific performance.

Genotoxic Agents Produce Stressor-Specific Spectra of Spectinomycin Resistance Mutations Based on Mechanism of Action and Selection in Bacillus subtilis.

Mutagenesis is integral for bacterial evolution and the development of antibiotic resistance. Environmental toxins and stressors are known to elevate the rate of mutagenesis through direct DNA toxicity, known as stress-associated mutagenesis, or via a more general stress-induced process that relies on intrinsic bacterial pathways. Here, we characterize the spectra of mutations induced by an array of different stressors using high-throughput sequencing to profile thousands of spectinomycin-resistant colonies of Bacillus subtilis. We found 69 unique mutations in the rpsE and rpsB genes, and that each stressor leads to a unique and specific spectrum of antibiotic-resistance mutations. While some mutations clearly reflected the DNA damage mechanism of the stress, others were likely the result of a more general stress-induced mechanism. To determine the relative fitness of these mutants under a range of antibiotic selection pressures, we used multistrain competitive fitness experiments and found an additional landscape of fitness and resistance. The data presented here support the idea that the environment in which the selection is applied (mutagenic stressors that are present), as well as changes in local drug concentration, can significantly alter the path to spectinomycin resistance in B. subtilis.

Dual Procurement of Lung and Heart Allografts Does Not Negatively Affect Lung Transplant Outcomes.

BACKGROUND: The data that exists regarding multiorgan procurement outcomes is conflicted. Given the increasing demand for pulmonary allografts, it is critical to assess the impact of dual procurement on lung transplant recipient outcomes. METHODS: The United Network for Organ Sharing transplant registry was queried for all first-time adult (age ≥18) lung transplant recipients between 2006 and 2018 and stratified by concurrent heart donor status. Multiorgan transplant recipients and recipients with missing survival time were excluded. Donors were excluded if they were donating after circulatory death, did not consent or were not approached for heart donation, the heart was recovered for nontransplant purposes, or the heart was recovered for transplant but not transplanted. Post-transplant survival was analyzed using the Kaplan-Meier method and multivariable Cox proportional hazards regression. RESULTS: A total of 18,641 recipients met inclusion criteria, including 6230 (33.4%) in the nonheart donor group (NHD) and 12,409 (66.6%) in the heart donor group (HD). HD recipients demonstrated longer survival at 10 years posttransplant, with a median survival of 6.5 years as compared with 5.9 years in NHD recipients. On adjusted analysis, HD and NHD recipients demonstrated comparable survival (AHR 0.95, 95% CI 0.90-1.01). CONCLUSIONS: Concomitant heart and lung procurement was not associated with worse survival. This finding encourages maximizing the number of organs procured from each donor, particularly in the setting of urgency-driven thoracic transplantation.

Aggressive pursuit and utilization of non-ideal donor lungs does not compromise post-lung transplant survival.

BACKGROUND: Organ procurement organizations (OPOs) vary in willingness to pursue and utilize non-ideal donor lungs; implications of these practices for lung transplant (LTx) recipients remain unclear. We examined associations between OPO-level behavior toward non-ideal donors and post-LTx outcomes. METHODS: Adult lung donors and corresponding adult first-time LTx recipients in the 2008-2019 UNOS registry were included. Non-ideal donors had any of age > 50, smoking history ≥20 pack-years, PaO2 /FiO2 ratio ≤350, donation after circulatory death, or increased risk status. OPOs were classified as least, moderately, or most aggressive based on non-ideal donor pursuit, consent attainment, lung recovery, and transplantation. Post-transplant outcomes were compared among aggressiveness strata. RESULTS: Of 22,795 recipients, 6229 (27.3%), 8256 (36.2%), and 8310 (36.5%) received lungs from least, moderately, and most aggressive OPOs, respectively. Moderately aggressive OPOs had the highest recipient rates of pre-discharge acute rejection, grade 3 primary graft dysfunction, postoperative extracorporeal membrane oxygenation, and longest lengths of stay. After adjustment, moderately and most aggressive OPOs had similar risks of recipient mortality as least aggressive OPOs. CONCLUSIONS: The most and least aggressive OPOs achieve similar patient survival and short-term post-LTx outcomes. Aggressive pursuit and utilization of non-ideal donor lungs by less aggressive OPOs would likely expand the donor pool, without compromising recipient outcomes.

B cells in transplant tolerance and rejection: friends or foes?

Our understanding of the role of B cells in organ transplantation remains incomplete and continues to grow. The majority of research has focused on the detrimental role of antibodies that drive the development of pathogenesis of the transplanted organ. However, it has been shown that not all donor-specific antibodies are harmful and in some circumstances can even promote tolerance through the mechanism of accommodation. Furthermore, B cells can have effects on transplanted organs through their interaction with T cells, namely antigen presentation, cytokine production, and costimulation. More recently, the role and importance of Bregs was introduced to the field of transplantation. Due to this functional and ontogenetic heterogeneity, targeting B cells in transplantation may bring undesired immunologic side effects including increased rejection. Therefore, the selective control of B cells that contribute to the humoral response against donor antigens will continue to be an important and challenging area of research and potentially lead to improved long-term transplant outcomes.

The past, present, and future of costimulation blockade in organ transplantation.

PURPOSE OF REVIEW: Manipulating costimulatory signals has been shown to alter T cell responses and prolong graft survival in solid organ transplantation. Our understanding of and ability to target various costimulation pathways continues to evolve. RECENT FINDINGS: Since the approval of belatacept in kidney transplantation, many additional biologics have been developed targeting clinically relevant costimulation signaling axes including CD40-CD40L, inducible costimulator-inducible costimulator ligand (ICOS-ICOSL), and OX40-OX40L. Currently, the effects of costimulation blockade on posttransplant humoral responses, tolerance induction, and xenotransplantation are under active investigation. Here, we will discuss these pathways as well as preclinical and clinical outcomes of biologics targeting these pathways in organ transplantation. SUMMARY: Targeting costimultion is a promising approach for not only controlling T cell but also B cell responses. Consequently, costimulation blockade shows considerable potential for improving outcomes in antibody-mediated rejection and xenotransplantation.

Regulation of stress-induced sleep fragmentation by preoptic glutamatergic neurons.

Sleep disturbances are detrimental to our behavioral and emotional well-being. Stressful events disrupt sleep, in particular by inducing brief awakenings (microarousals, MAs), resulting in sleep fragmentation. The preoptic area of the hypothalamus (POA) is crucial for sleep control. However, how POA neurons contribute to the regulation of MAs and thereby impact sleep quality is unknown. Using fiber photometry in mice, we examine the activity of genetically defined POA subpopulations during sleep. We find that POA glutamatergic neurons are rhythmically activated in synchrony with an infraslow rhythm in the spindle band of the electroencephalogram during non-rapid eye movement sleep (NREMs) and are transiently activated during MAs. Optogenetic stimulation of these neurons promotes MAs and wakefulness. Exposure to acute social defeat stress fragments NREMs and significantly increases the number of transients in the calcium activity of POA glutamatergic neurons during NREMs. By reducing MAs, optogenetic inhibition during spontaneous sleep and after stress consolidates NREMs. Monosynaptically restricted rabies tracing reveals that POA glutamatergic neurons are innervated by brain regions regulating stress and sleep. In particular, presynaptic glutamatergic neurons in the lateral hypothalamus become activated after stress, and stimulating their projections to the POA promotes MAs and wakefulness. Our findings uncover a novel circuit mechanism by which POA excitatory neurons regulate sleep quality after stress.

Comparison of Patterns and Demographics of Isolated Traumatic Mandibular Fracture Between Incarcerated and General Populations.

Introduction The management of maxillofacial trauma can be challenging in different unique clinical presentations. While maxillofacial fractures vary in location based on the mechanism of injury, the mandibular fracture is noted to be one of the most common facial fractures. The objective of this study was to explore the differences in injury patterns, outcomes, and demographics of isolated traumatic mandibular fractures between incarcerated and general populations. Methods This retrospective study analyzed consecutive patients presenting for trauma care from January 1, 2010, to December 31, 2020, at the Arrowhead Regional Medical Center (ARMC). Patients 18 years and older were included in this study. Patients diagnosed with mandibular fracture as the primary diagnosis at admission and discharge were identified using the International Classification of Disease, Ninth and Tenth Revision (ICD-9, ICD-10) Code. Patient demographics were extracted from their electronic medical records and included race, marital status, and insurance status. Results A total of 1080 patients with confirmed mandibular fractures were included in the final analysis. Among these patients, 87.5% (n=945) were males, 40% (n=432) of the patients were Hispanic, and the average age was 31.55 years old. The most common mechanism of injury was blunt trauma secondary to assault. Compared to the general population with mandibular fracture, the incarcerated patients with mandibular fracture were more likely to be males (96.1% vs 86.1% for incarcerated population vs. general population respectively, p=0.0005). No other variables were statistically different between these two groups. Conclusion The evidence from this study suggests that the patterns, outcomes, and demographics of mandibular fracture in both incarcerated and general populations are similar.

Circuit mechanism underlying fragmented sleep and memory deficits in 16p11.2 deletion mouse model of autism.

Sleep disturbances are prevalent in children with autism spectrum disorder (ASD) and have a major impact on the quality of life. Strikingly, sleep problems are positively correlated with the severity of ASD symptoms, such as memory impairment. However, the neural mechanisms underlying sleep disturbances and cognitive deficits in ASD are largely unexplored. Here, we show that non-rapid eye movement sleep (NREMs) is highly fragmented in the 16p11.2 deletion mouse model of ASD. The degree of sleep fragmentation is reflected in an increased number of calcium transients in the activity of locus coeruleus noradrenergic (LC-NE) neurons during NREMs. Exposure to a novel environment further exacerbates sleep disturbances in 16p11.2 deletion mice by fragmenting NREMs and decreasing rapid eye movement sleep (REMs). In contrast, optogenetic inhibition of LC-NE neurons and pharmacological blockade of noradrenergic transmission using clonidine reverse sleep fragmentation. Furthermore, inhibiting LC-NE neurons restores memory. Rabies-mediated unbiased screening of presynaptic neurons reveals altered connectivity of LC-NE neurons with sleep- and memory regulatory brain regions in 16p11.2 deletion mice. Our findings demonstrate that heightened activity of LC-NE neurons and altered brain-wide connectivity underlies sleep fragmentation in 16p11.2 deletion mice and identify a crucial role of the LC-NE system in regulating sleep stability and memory in ASD.

Cellular therapeutics and immunotherapies in wound healing - on the pulse of time?

Chronic, non-healing wounds represent a significant challenge for healthcare systems worldwide, often requiring significant human and financial resources. Chronic wounds arise from the complex interplay of underlying comorbidities, such as diabetes or vascular diseases, lifestyle factors, and genetic risk profiles which may predispose extremities to local ischemia. Injuries are further exacerbated by bacterial colonization and the formation of biofilms. Infection, consequently, perpetuates a chronic inflammatory microenvironment, preventing the progression and completion of normal wound healing. The current standard of care (SOC) for chronic wounds involves surgical debridement along with localized wound irrigation, which requires inpatient care under general anesthesia. This could be followed by, if necessary, defect coverage via a reconstructive ladder utilizing wound debridement along with skin graft, local, or free flap techniques once the wound conditions are stabilized and adequate blood supply is restored. To promote physiological wound healing, a variety of approaches have been subjected to translational research. Beyond conventional wound healing drugs and devices that currently supplement treatments, cellular and immunotherapies have emerged as promising therapeutics that can behave as tailored therapies with cell- or molecule-specific wound healing properties. However, in contrast to the clinical omnipresence of chronic wound healing disorders, there remains a shortage of studies condensing the current body of evidence on cellular therapies and immunotherapies for chronic wounds. This review provides a comprehensive exploration of current therapies, experimental approaches, and translational studies, offering insights into their efficacy and limitations. Ultimately, we hope this line of research may serve as an evidence-based foundation to guide further experimental and translational approaches and optimize patient care long-term.

Circuit mechanism underlying fragmented sleep and memory deficits in 16p11.2 deletion mouse model of autism.

Sleep disturbances are prevalent in children with autism spectrum disorder (ASD) and have a major impact on the quality of life. Strikingly, sleep problems are positively correlated with the severity of ASD symptoms, such as memory impairment. However, the neural mechanisms underlying sleep disturbances and cognitive deficits in ASD are largely unexplored. Here, we show that non-rapid eye movement sleep (NREMs) is highly fragmented in the 16p11.2 deletion mouse model of ASD. The degree of sleep fragmentation is reflected in an increased number of calcium transients in the activity of locus coeruleus noradrenergic (LC-NE) neurons during NREMs. Exposure to a novel environment further exacerbates sleep disturbances in 16p11.2 deletion mice by fragmenting NREMs and decreasing rapid eye movement sleep (REMs). In contrast, optogenetic inhibition of LC-NE neurons and pharmacological blockade of noradrenergic transmission using clonidine reverse sleep fragmentation. Furthermore, inhibiting LC-NE neurons restores memory. Rabies-mediated unbiased screening of presynaptic neurons reveals altered connectivity of LC-NE neurons with sleep- and memory regulatory brain regions in 16p11.2 deletion mice. Our findings demonstrate that heightened activity of LC-NE neurons and altered brain-wide connectivity underlies sleep fragmentation in 16p11.2 deletion mice and identify a crucial role of the LC-NE system in regulating sleep stability and memory in ASD.

Sleep disturbances in autism spectrum disorder: Animal models, neural mechanisms, and therapeutics.

Sleep is crucial for brain development. Sleep disturbances are prevalent in children with autism spectrum disorder (ASD). Strikingly, these sleep problems are positively correlated with the severity of ASD core symptoms such as deficits in social skills and stereotypic behavior, indicating that sleep problems and the behavioral characteristics of ASD may be related. In this review, we will discuss sleep disturbances in children with ASD and highlight mouse models to study sleep disturbances and behavioral phenotypes in ASD. In addition, we will review neuromodulators controlling sleep and wakefulness and how these neuromodulatory systems are disrupted in animal models and patients with ASD. Lastly, we will address how the therapeutic interventions for patients with ASD improve various aspects of sleep. Together, gaining mechanistic insights into the neural mechanisms underlying sleep disturbances in children with ASD will help us to develop better therapeutic interventions.

The Pterional Keyhole Craniotomy Approach: A Historical Perspective.

The pterional craniotomy is a workhorse of cranial surgery that provides access to the anterior and middle fossae. However, newer "keyhole" approaches, such as the micropterional or pterional keyhole craniotomy (PKC) can offer similar exposure for many pathologies while reducing surgical morbidity. The PKC is associated with shorter hospitalizations, reduced operative time, and superior cosmetic outcomes. Furthermore, it represents an ongoing trend toward smaller craniotomy size for elective cranial procedures. In this historical vignette, we trace the history of the PKC from its origins to its current role in the neurosurgeon's armamentarium.

Comparison of Male and Female Surgeons' Experiences With Gender Across 5 Qualitative/Quantitative Domains.

Importance: A growing body of literature has been developed with the goal of attempting to understand the experiences of female surgeons. While it has helped to address inequities and promote important programmatic improvements, work remains to be done. Objective: To explore how practicing male and female surgeons' experiences with gender compare across 5 qualitative/quantitative domains: career aspirations, gender-based discrimination, mentor-mentee relationships, perceived barriers, and recommendations for change. Design, Setting, and Participants: This national concurrent mixed-methods survey of Fellows of the American College of Surgeons (FACS) compared differences between male and female FACS. Differences between female FACS and female members of the Association of Women Surgeons (AWS) were also explored. A randomly selected 3:1 sample of US-based male and female FACS was surveyed between January and June 2020. Female AWS members were surveyed in May 2020. Exposure: Self-reported gender. Main Outcomes and Measures: Self-reported experiences with career aspirations (quantitative), gender-based discrimination (quantitative), mentor-mentee relationships (quantitative), perceived barriers (qualitative), and recommendations for change (qualitative). Results: A total of 2860 male FACS (response rate: 38.1% [2860 of 7500]) and 1070 female FACS (response rate: 42.8% [1070 of 2500]) were included, in addition to 536 female AWS members. Demographic characteristics were similar between randomly selected male and female FACS, with the notable exception that female FACS were less likely to be married (720 [67.3%] vs 2561 [89.5%]; nonresponse-weighted P < .001) and have children (660 [61.7%] vs 2600 [90.9%]; P < .001). Compared with female FACS, female AWS members were more likely to be younger and hold additional graduate degrees (320 [59.7%] were married; 238 [44.4%] had children). FACS of both genders acknowledged positive and negative aspects of dealing with gender in a professional setting, including shared experiences of gender-based harassment, discrimination, and blame. Female FACS were less likely to have had gender-concordant mentors. They were more likely to emphasize the importance of gender when determining career aspirations and prioritizing future mentor-mentee relationships. Moving forward, female FACS emphasized the importance of avoiding competition among female surgeons. They encouraged male surgeons to acknowledge gender bias and admit their potential role. Male FACS encouraged male and female surgeons to treat everyone the same. Conclusions and Relevance: Experiences with gender are not limited to supportive female surgeons. The results of this study emphasize the importance of recognizing the voices of all stakeholders involved when striving to promote workforce diversity and the related need to develop quality improvement/surgical education initiatives that enhance inclusion through open, honest discourse.