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Abstract Introduction Breast cancer treatment patterns and quality of care among patients experiencing incarceration are underexplored. This study examined associations between incarceration and breast cancer disease and treatment characteristics. Methods This retrospective analysis was conducted at a tertiary center in the Southeastern United States that serves as the state's safety‐net hospital and primary referral site for the state's prisons. All patients ≥18 years diagnosed with breast cancer between 4/14/2014–12/30/2020 were included. Incarceration status was determined through electronic health record review. Linear regression was used to estimate the association of incarceration with time to treatment. Unadjusted overall survival (OS) was estimated using the Kaplan–Meier method with log‐rank tests to compare groups. Results Of the 4329 patients included, 30 (0.7%) were incarcerated at the time of diagnosis or treatment (DI) and 4299 (99.3%) had no incarceration history (NI). Compared to patients who were NI, patients who were DI were younger (p

Objectives Medical schools have sought to incorporate concepts of race and racism in their curricula to facilitate students’ abilities to grapple with healthcare disparities in the United States; however, these efforts frequently fail to address implicit bias or equip students with cultural humility, reflective capacity, and interpersonal skills required to navigate racialized systems in healthcare. The purpose of this study was to develop and evaluate an antiracism narrative medicine (NM) program designed by and for preclinical medical students. Method Preclinical medical students at a single center were eligible to participate from June-July 2021. Program evaluation included a postprogram qualitative interview and electronic survey. The semistructured interview included questions about program experience, lessons learned, and perspectives on antiracism curricula in medical education. Interviews were qualitatively analyzed using open and axial coding. Survey data were analyzed with descriptive statistics. Results A total of 30 students registered. All (100%) respondents reported “somewhat true” or “very true” in the postprogram survey when asked about their ability to reflect on their own racial identity, racial identity of others, and influence of their racial identity on their future role as a healthcare worker through the program. Qualitative analysis revealed 3 themes: (1) curricular engagement; (2) racism and antiracism in medicine; and (3) group experience. Subthemes included: meaningful theoretical content; multimodal works and unique perspectives; race, identity, and intersectionality; deeper diversity, equity, and inclusion engagement; reconstructive visions; future oriented work; close reading and writing build confidence in discomfort; community and support system; and authentic space among peer learners. Conclusion This virtual, peer-facilitated antiracism NM program provided an engaging and challenging experience for participants. Postprogram interviews revealed the program deepened students’ understanding of racism, promoted self-reflection and community building, and propagated reconstructive visions for continuing antiracism work.

Background: Immune checkpoint inhibitors (ICIs) can induce immune-related adverse events (irAEs). Liquid biomarkers to predict irAE occurrence are urgently needed. We previously developed an ELISA system to specifically detect soluble PD-L1 (sPD-L1) with PD-1-binding capacity (bsPD-L1). Here, we investigated the relationship between sPD-L1 and bsPD-L1 in gastric cancer (GC) and non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 blockade and their association with irAEs.Methods: We examined sPD-L1, bsPD-L1, matrix metalloproteinases (MMPs), and proinflammatory cytokine levels by ELISA in plasma samples from 117 GC patients prior to surgery and 72 NSCLC patients prior to and at 2 months after ICI treatment (anti-PD-1, n = 48; anti-PD-L1, n = 24). In mice treated with anti-PD-1/PD-L1 antibodies (Abs), sPD-L1 levels and localization of Abs were examined by ELISA and immunohistochemistry, respectively.Results:sPD-L1 was detected with higher frequency in GC patients than in NSCLC patients, whereas bsPD-L1 was detected with similar frequencies in GC and NSCLC patients. sPD-L1 levels were correlated with IL-1α, IL-1β, TNF-α, and IL-6 levels, while bsPD-L1 levels were correlated with MMP13, MMP3, and IFN-γ levels. In NSCLC patients, anti-PD-L1, but not anti-PD-1, treatment increased sPD-L1, which was associated with irAE development, but not with clinical outcomes. In mice, trafficking of anti-PD-L1 Abs to lysosomes in F4/80+ macrophages resulted in sPD-L1 production, which was suppressed by treatment with lysosomal degradation inhibitor chloroquine and macrophage depletion.Conclusion: Anti-PD-L1-mediated lysosomal degradation induces sPD-L1 production, which can serve as an indicator to predict irAE development during anti-PD-L1 treatment.

BackgroundThe tumor microenvironment (TME) impacts the therapeutic efficacy of immune checkpoint inhibitors (ICIs). No liquid biomarkers are available to evaluate TME heterogeneity. Here, we investigated the clinical significance of PD-1-binding soluble PD-L1 (bsPD-L1) in gastric cancer (GC) patients and non-small cell lung cancer (NSCLC) patients treated with PD-1/PD-L1 blockade.MethodsWe examined bsPD-L1, matrix metalloproteinases (MMPs), and IFN-γ levels in plasma samples from GC patients (n = 117) prior to surgery and NSCLC patients (n = 72) prior to and 2 months after ICI treatment. We also examined extracellular matrix (ECM) integrity, PD-L1 expression, and T cell infiltration in tumor tissues from 25 GC patients by Elastica Masson-Goldner staining and immunohistochemical staining for PD-L1 and CD3, respectively.ResultsbsPD-L1 was detected in 17/117 GC patients and 16/72 NSCLC patients. bsPD-L1 showed strong or moderate correlations with plasma MMP13 or MMP3 levels, respectively, in both GC and NSCLC patients. bsPD-L1 expression in GC was associated with IFN-γ levels and intra-tumoral T cell infiltration, whereas MMP13 levels were associated with loss of ECM integrity, allowing tumor cells to access blood vessels. Plasma MMP3 and MMP13 levels were altered during ICI treatment. Combined bsPD-L1 and MMP status had higher predictive accuracy to identify two patient groups with favorable and poor prognosis than tumor PD-L1 expression: bsPD-L1+MMP13high in GC and bsPD-L1+(MMP3 and MMP13)increased in NSCLC were associated with poor prognosis, whereas bsPD-L1+MMP13low in GC and bsPD-L1+(MMP3 or MMP13)decreased in NSCLC were associated with favorable prognosis.ConclusionPlasma bsPD-L1 and MMP13 levels indicate T cell response and loss of ECM integrity, respectively, in the TME. The combination of bsPD-L1 and MMPs may represent a non-invasive tool to predict recurrence in GC and the efficacy of ICIs in NSCLC.

Background: The current National Comprehensive Cancer Network advises neoadjuvant chemoradiotherapy followed by surgery for locally advanced cases of esophageal cancer. The role of immunotherapy in this context is under heavy investigation. Methods: Patients with esophageal adenocarcinoma were identified in the National Cancer Database (NCDB) from 2004 to 2019. Three groups were generated as follows: (a) no immunotherapy, (b) neoadjuvant immunotherapy, and (c) adjuvant immunotherapy. Overall survival was evaluated using the Kaplan–Meier method and Cox proportional hazard analysis, adjusting for previously described risk factors for mortality. Results: Of the total 14,244 patients diagnosed with esophageal adenocarcinoma who received neoadjuvant chemoradiation, 14,065 patients did not receive immunotherapy, 110 received neoadjuvant immunotherapy, and 69 received adjuvant immunotherapy. When adjusting for established risk factors, adjuvant immunotherapy was associated with significantly improved survival compared to no immunotherapy and neoadjuvant immunotherapy during a median follow-up period of 35.2 months. No difference was noted among patients who received no immunotherapy vs. neoadjuvant immunotherapy in the same model. Conclusions: In this retrospective analysis of the NCDB, receiving adjuvant immunotherapy offered a significant survival advantage compared to no immunotherapy and neoadjuvant immunotherapy in the treatment of esophageal adenocarcinoma. The addition of neoadjuvant immunotherapy to patients treated with neoadjuvant chemoradiation did not improve survival in this cohort. Further studies are warranted to investigate the long-term outcomes of immunotherapy in esophageal cancer.

Abstract Background Policies for next-of-kin (NOK) notification and disposition of remains surrounding death are unclear across the United States’ (US) carceral systems. The goal of this study was to collect data on carceral system policies pertaining to NOK notification and disposition of remains for individuals who are incarcerated. We collected publicly available operational policies for the Federal Bureau of Prisons, Immigration and Customs Enforcement, 50 state prison systems, and the Washington D.C. jail for a total of 53 systems. Results Approximately 70% of systems had available policies on NOK notification and disposition of remains. Few systems had information on time constraints for NOK notification, notifying parties or designated contacts person, and ultimate disposition of unclaimed remains. Several systems had no accessible policies. Conclusions Across the US, carceral systems vary in policies for notifying NOK after the death of an incarcerated individual and their processes for the disposition of remains. Carceral and health systems should work towards standardization of policies on communication and disposition of remains after death of an individual who is incarcerated to work towards equity.

PURPOSEDespite the disproportionately high risk of breast cancer among women of African heritage, little is known about the facilitators and barriers to implementing germline genetic testing and counseling (GT/C).METHODSThis scoping review followed guidelines recommended by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. Published manuscripts from database inception through 2021 were sourced from PubMed, Cumulative Index to Nursing and Allied Health Literature via EBSCO, Embase, Cochrane Library, and Scopus. Search terms were used to retrieve articles addressing (1) African heritage, (2) breast cancer, and (3) GT or GC. The screening involved abstract and title review and full-text review. Data were extracted for all articles meeting the inclusion criteria.RESULTSA total of 154 studies were included. Most studies that took place were conducted in the United States (71.4%), and most first authors (76.9%) were from the United States. GT was conducted in 73 (49.7%) studies. BRCA1/BRCA2 were the most commonly studied genes for germline mutations. GC was conducted in 49 studies (33.3%), and perspectives on GC were evaluated in 43 (29.3%). The use of racial/ethnic categories varied broadly, although African American was most common (40.1%). Racism was mentioned in three studies (2.0%).CONCLUSIONThere is a growing body of literature on GT/C for breast cancer in women of African heritage. Future studies on GT/C of African populations should consider increased clarity around racial/ethnic categorizations, continued community engagement, and intentional processes for informed consent.

The United States (U.S.) health professions are becoming more invested in diversity. Information on students who are undocumented or recipients of Deferred Action for Childhood Arrivals (DACA), and international students on student visas entering U.S. medical education is sparse. Few programs offer targeted training for educators on advising students who are undocumented, DACA recipients, or on a visa. We piloted a virtual program for pre-health advisors and educators on supporting students who are undocumented or recipients of DACA and international students transitioning to medical school. Program evaluation consisted of an anonymous retrospective pre-post survey. Of 117 registrants, 40% completed the survey. Prior to the program, most participants indicated that they were unsure or thought students were ineligible for financial aid during medical school if they were DACA recipients (40% unsure, 26.6% ineligible) or on a student visa (30% unsure, 30% ineligible). After the program, most respondents reported students were eligible for merit scholarship or private loans with DACA (66.6% eligible) or an international student visa (60% eligible). Perceptions of students with DACA being able to lawfully practice medicine in the U.S. changed from pre-program (43.3% unsure or not eligible) to post-program (90% eligible). Participants indicated they were more confident advising DACA recipients and international students post program. This virtual program was an effective step in providing support for advisors who are assisting non-citizen or permanent resident students start their careers in healthcare. Our findings show the need for more information on advising students who are DACA recipients, undocumented, or on student visas prior to matriculating to medical school and throughout training.

Brain dopamine is critical for normal motor control, as evidenced by its importance in Parkinson Disease and related disorders. Current hypotheses are that dopamine influences motor control by ‘invigorating’ movements and regulating motor learning. Most evidence for these aspects of dopamine function comes from simple tasks (e.g. lever pressing). Therefore, the influence of dopamine on motor skills requiring multi-joint coordination is unknown. To determine the effects of precisely timed dopamine manipulations on the performance of a complex, finely coordinated dexterous skill, we optogenetically stimulated or inhibited midbrain dopamine neurons as rats performed a skilled reaching task. We found that reach kinematics and coordination between gross and fine movements progressively changed with repeated manipulations. However, once established, rats transitioned abruptly between aberrant and baseline reach kinematics in a dopamine-dependent manner. These results suggest that precisely timed dopamine signals have immediate and long-term influences on motor skill performance, distinct from simply ‘invigorating’ movement.

Narrative medicine workshops are typically conducted in person and provide medical professionals and students with reflective spaces. During the COVID-19 pandemic, in-person workshops at one university were cancelled and moved online following social distancing measures. Narrative medicine workshop facilitators were challenged to transfer workshops online, while still encouraging creative reflection as the pandemic impacted participants' professional and personal lives. One workshop for pre-medical students at the university moved online to Zoom, the standard platform for all university courses. The workshop length was shortened and the curriculum re-focused on creative texts and personal wellbeing. Participants responded positively to Zoom workshops although fewer individuals participated overall. Most participants were able to successfully use the platform although there were difficulties regarding WiFi and connection. Despite challenges, these workshops function in virtual spaces and provide an important opportunity for programs to integrate virtual sessions for wellness and reflection during a time of pandemic.

Abstract Immunotherapy has recently emerged as the fourth pillar of cancer treatment, joining surgery, radiation, and chemotherapy. While early immunotherapies focused on accelerating T-cell activity, current immune-checkpoint inhibitors take the brakes off the anti-tumor immune responses. Successful clinical trials with PD-1 monoclonal antibodies and other immune-checkpoint inhibitors have opened new avenues in cancer immunology. However, the failure of a large subset of cancer patients to respond to these new immunotherapies has led to intensified research on combination therapies and predictive biomarkers. Here we summarize the development of PD-1-blockade immunotherapy and current issues in its clinical use.

Rapid proliferation is one of the important features of memory CD8(+) T cells, ensuring rapid clearance of reinfection. Although several cytokines such as IL-15 and IL-7 regulate relatively slow homeostatic proliferation of memory T cells during the maintenance phase, it is unknown how memory T cells can proliferate more quickly than naïve T cells upon antigen stimulation. To examine antigen-specific CD8(+) T cell proliferation in recall responses in vivo, we targeted a model antigen, ovalbumin(OVA), to DEC-205(+) dendritic cells (DCs) with a CD40 maturation stimulus. This led to the induction of functional memory CD8(+) T cells, which showed rapid proliferation and multiple cytokine production (IFN-gamma, IL-2, TNF-alpha) during the secondary challenge to DC-targeted antigen. Upon antigen-presentation, IL-18, an IFN-gamma-inducing factor, accumulated at the DC:T cell synapse. Surprisingly, IFN-gamma receptors were required to augment IL-18 production from DCs. Mice genetically deficient for IL-18 or IFN-gamma-receptor 1 also showed delayed expansion of memory CD8(+) T cells in vivo. These results indicate that a positive regulatory loop involving IFN-gamma and IL-18 signaling contributes to the accelerated memory CD8(+) T cell proliferation during a recall response to antigen presented by DCs.

Objective: To compare the representation of intersectional (ie, racial/ ethnic and gender) identities among surgical faculty versus medical students. Background: Health disparities are pervasive in medicine, but diverse physicians may help the medical profession achieve health equity. Methods: Data from the Association of American Medical Colleges for 140 programs (2011/2012-2019/2020) were analyzed for students and full-time surgical faculty. Underrepresented in medicine (URiM) was defined as Black/African American, American Indian/Alaskan Native, Hispanic/Latino/Spanish Origin, or Native Hawaiian/Other Pacific Islander. Non-White included URiM plus Asian, multiracial, and non-citizen permanent residents. Linear regression was used to estimate the association of year and proportions of URiM and non-White female and male faculty with proportions of URiM and non-White students. Results: Medical students were comprised of more White (25.2% vs 14.4%), non-White (18.8% vs 6.6%), and URiM (9.6% vs 2.8%) women and concomitantly fewer men across all groups versus faculty (all P < 0.01). Although the proportion of White and non-White female faculty increased over time (both P ≤ 0.001), there was no significant change among non-White URiM female faculty, nor among non-White male faculty, regardless of whether they were URiM or not. Having more URiM male faculty was associated with having more non-White female students (estimate = +14.5% students/100% increase in faculty, 95% CI: 1.0% to 8.1%, P = 0.04), and this association was especially pronounced for URiM female students (estimate = +46.6% students/100% increase in faculty, 95% CI: 36.9% to 56.3%, P < 0.001). Conclusions: URiM faculty representation has not improved despite a positive association between having more URiM male faculty and having more diverse students. [ABSTRACT FROM AUTHOR]

BACKGROUND: Impostor syndrome is an internalized sense of incompetence and not belonging. We examined associations between impostor syndrome and holding leadership positions in medicine. STUDY DESIGN: A cross-sectional survey was distributed to US physicians from June 2021 to December 2021 through medical schools and professional organizations. Differences were tested with the chi-square test and i-test for categorical and continuous variables, respectively. Logistic regression was used to identify factors associated with holding leadership positions and experiencing impostor syndrome. RESULTS: A total of 2,183 attending and retired physicians were included in the analytic cohort; 1,471 (67.4%) were in leadership roles and 712 (32.6%) were not. After adjustment, male physicians were more likely than women to hold leadership positions (odds ratio 1.4; 95% CI 1.16 to 1.69; p < 0.001). Non-US citizens (permanent resident or visa holder) were less likely to hold leadership positions than US citizens (odds ratio 0.3; 95% CI 0.16 to 0.55; p < 0.001). Having a leadership position was associated with lower odds of impostor syndrome (odds ratio 0.54; 95% CI 0.43 to 0.68; p < 0.001). Female surgeons were more likely to report impostor syndrome compared to male surgeons (90.0% vs 67.7%; p < 0.001), an association that persisted even when female surgeons held leadership roles. Similar trends were appreciated for female and male nonsurgeons. Impostor syndrome rates did not differ by race and ethnicity, including among those underrepresented in medicine, even after adjustment for gender and leadership role. CONCLUSIONS: Female physicians were more likely to experience impostor syndrome than men, regardless of specialty or leadership role. Although several identity-based gaps persist in leadership, impostor syndrome among racially minoritized groups may not be a significant contributor. [ABSTRACT FROM AUTHOR]

In 2020, the authors of this article published "Abolition Medicine" as one contribution to international abolitionist conversations responding to widespread anti-Black police violence and inequity laid bare by the COVID-19 pandemic. Over the past year, there has been a surge of efforts to abolish deeply embedded patterns of race-based oppression in policing and incarceration in the United States. In this essay, the authors continue to explore how health care can join these conversations and move toward a praxis of health justice. Using the framework of Ruth Wilson Gilmore's organized abandonment, the article revisits grassroots organizations and efforts that have been engaging in abolitionist health care all along. It also looks to current and emerging abolitionist policies and practices operating at the margins of status quo health care for models of abolition in medicine. [ABSTRACT FROM AUTHOR]