Phenotypic signatures of circulating neoantigen-reactive CD8+ T cells in patients with metastatic cancers.

Circulating T cells from peripheral blood (PBL) can provide a rich and noninvasive source for antitumor T cells. By single-cell transcriptomic profiling of 36 neoantigen-specific T cell clones from 6 metastatic cancer patients, we report the transcriptional and cell surface signatures of antitumor PBL-derived CD8+ T cells (NeoTCRPBL). Comparison of tumor-infiltrating lymphocyte (TIL)- and PBL-neoantigen-specific T cells revealed that NeoTCRPBL T cells are low in frequency and display less-dysfunctional memory phenotypes relative to their TIL counterparts. Analysis of 100 antitumor TCR clonotypes indicates that most NeoTCRPBL populations target the same neoantigens as TILs. However, NeoTCRPBL TCR repertoire is only partially shared with TIL. Prediction and testing of NeoTCRPBL signature-derived TCRs from PBL of 6 prospective patients demonstrate high enrichment of clonotypes targeting tumor mutations, a viral oncogene, and patient-derived tumor. Thus, the NeoTCRPBL signature provides an alternative source for identifying antitumor T cells from PBL of cancer patients, enabling immune monitoring and immunotherapies.

Building Organizational Capacity to Deliver Oncology Financial Advocacy.

Background: Cancer-related financial hardship is linked to poor health outcomes and early mortality. Oncology financial advocacy (OFA) aims to prevent cancer-related financial hardship in oncology settings by assessing patients' needs and connecting them to available financial resources. Despite promising evidence, OFA remains underutilized. Objectives: Describe oncology financial advocates' perceptions about the challenges to and opportunities for implementing oncology financial advocacy (OFA) in community cancer centers. Methods: Nine virtual focus groups were conducted with 45 oncology financial advocates. Focus group transcripts were analyzed using template-based thematic analysis informed by the Consolidated Framework for Implementation Research (CFIR); two study team members coded each transcript and all six team members identified emergent themes. Results: Salient themes were identified across all five domains of the CFIR framework: (1) intervention characteristics: participants described challenges of adapting OFA to meet the needs of the medical system instead of needs of the patients; (2) outer setting: growing awareness of health and cancer disparities could bring more attention to and investment in OFA; (3) inner setting: programs are under-resourced to assist all at-risk patients, staffing, technology integration, and network/communication workflows are needed; (4) characteristics of individuals: advocates believe strongly in the effectiveness and would like to see their credibility enhanced with professional certification; (5) process: implementation strategies that target the engagement of leadership, key stakeholders, and patients to increase program reach are needed. Conclusions: OFA cannot reach all at-risk patients because of understaffing, poor communication between departments, and a lack of understanding OFA as an intervention among colleagues, key stakeholders, and patients. To reach full implementation, advocates need assistance in making the case for more resources, research on patient outcomes, professional certification, and the use of policy to incentivize financial advocacy as a standard of care in medicine.

Influences on Lung Cancer Screening Initiation and Retention in Rural Alabama.

INTRODUCTION/OBJECTIVES: Despite the introduction of lung cancer screening using low dose computed tomography (LDCT), overall screening rates in the U.S. remain low, with certain populations including Black and rural communities experiencing additional disparities. The primary objective of this study was to understand the facilitators of lung cancer screening initiation and retention in Alabama reported by people at risk from mostly rural, mostly Black populations in Jefferson County-including the urban center of Birmingham-and 6 rural counties: Choctaw, Dallas, Greene, Hale, Marengo, and Sumter. METHODS: We conducted semi-structured telephone interviews with 58 people who underwent lung cancer screening between December 2019 and January 2022. Participant responses were recorded by the interviewer for analysis. Open-ended responses were coded to identify emergent themes. RESULTS: The most reported influences to initiate screening were information or suggestion from a Community Health Advisor (CHAs) or the supervising county coordinator, suggestion from a friend, or consideration of a personal history of smoking. Most participants reported multiple influences. Physicians were not very influential in decisions to initiate screening, but they were extremely influential in participants' intent to continue screening, both positively and negatively. Knowing the recommended timeline for their annual scans was also a predictor of intention to continue screening. Participants screened during the COVID-19 state of emergency expressed less certainty about dates of next scans and more ambivalence about intention to continue screening. CONCLUSIONS: This study shows the benefit of using multiple methods to support increased awareness of and interest in lung cancer screening, particularly when educational messaging through CHAs is used. Clear guideline-based messages from healthcare providers about recommended screening is important for increasing retention. COVID-19 related implementation challenges impacted screening recruitment and retention. Future research is warranted to further explore use of CHAs in lung cancer screening.

Risk Factors for Substance Use across the Lifespan.

Substance use is a perennial public health concern with associated health risks and economic impacts on society. In this article, we present a selective review of the epidemiological and clinical literatures on alcohol and substance use from a lifespan developmental perspective. We compare and contrast risk factors for the initiation of use and the development of a substance use disorder in adolescence, young adulthood, middle-age and later life. During adolescence, alcohol use experimentation is at its peak. Specific risk factors have been identified including trauma and parenting style that can increase the risk of substance use for teenagers. Emerging adults and college students are likely to experiment with other substances in addition to alcohol such as nicotine, marijuana, cocaine, and prescription medication such as Adderall. Middle-age and older adults with alcohol and substance use in their developmental histories may have an undiagnosed alcohol use disorder. Others will develop a late-onset substance use disorder in older age, possibly due to a dearth of social support, coping with bereavement, and medical complication. Based on Social Cognitive Theory, the roles of expectancies and self-efficacy are hypothesized to impact substance use and the risk of substance use disorder across the lifespan. Implications of the present review for future research on age-specific risk factors in alcohol use in relation to underlying developmental processes are considered.

The impact of depression on opioid withdrawal symptoms among smokers with opioid use disorder receiving medication-assisted opioid detoxification.

Individuals with opioid use disorder (OUD) endorse high rates of combustible smoking (Zale et al., 2015) which is associated with poorer outcomes (e.g., opioid craving and lower detoxification completion rates) among individuals receiving medications for opioid use disorder (MOUD; Mannelli et al., 2013) and lower smoking cessation rates (Okoli et al., 2010). The complex pharmacological relationship between opioids and nicotine may help explain these findings (Kohut, 2017); however, little is known about psychosocial variables that influence MOUD processes among combustible smokers with OUD. The present study sought to expand upon prior work (Mannelli et al., 2013) by examining the impact of psychological factors and smoking-related variables on opioid withdrawal symptoms among smokers with OUD receiving Suboxone at an inpatient substance use treatment facility. Current smokers with OUD (N = 64) completed a battery of psychological measures examining depression, anxiety, and smoking constructs. The present study tested the influence of daily smoking rate, nicotine dependence, smoking urges, anxiety, and depression on opioid withdrawal symptoms through a hierarchical multiple regression. Findings revealed that smoking urges (p = .003) predicted severity of opioid withdrawal symptoms while controlling for race, daily smoking rate, and nicotine dependence. Depression (p = .000), however, explained variance in severity of opioid withdrawal symptoms above and beyond all smoking-related variables and anxiety. Results highlight the importance of considering psychological factors, specifically depression, which impact treatment processes among smokers with OUD to help inform the development of effective treatment interventions for both OUD and smoking cessation among individuals with OUD. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Neoantigen Identification and Response to Adoptive Cell Transfer in Anti-PD-1 Naïve and Experienced Patients with Metastatic Melanoma.

PURPOSE: Immune checkpoint blockade (ICB) agents and adoptive cell transfer (ACT) of tumor-infiltrating lymphocytes (TIL) are prominent immunotherapies used for the treatment of advanced melanoma. Both therapies rely on activation of lymphocytes that target shared tumor antigens or neoantigens. Recent analysis of patients with metastatic melanoma who underwent treatment with TIL ACT at the NCI demonstrated decreased responses in patients previously treated with anti-PD-1 agents. We aimed to find a basis for the difference in response rates between anti-PD-1 naïve and experienced patients. PATIENTS AND METHODS: We examined the tumor mutational burden (TMB) of resected tumors and the repertoire of neoantigens targeted by autologous TIL in a cohort of 112 anti-PD-1 naïve and 69 anti-PD-1 experienced patients. RESULTS: Anti-PD-1 naïve patients were found to possess tumors with higher TMBs (352.0 vs. 213.5, P = 0.005) and received TIL reactive with more neoantigens (2 vs. 1, P = 0.003) compared with anti-PD-1 experienced patients. Among patients treated with TIL ACT, TMB and number of neoantigens identified were higher in ACT responders than ACT nonresponders in both anti-PD-1 naïve and experienced patients. Among patients with comparable TMBs and predicted neoantigen loads, treatment products administered to anti-PD-1 naïve patients were more likely to contain T cells reactive against neoantigens than treatment products for anti-PD-1 experienced patients (2.5 vs. 1, P = 0.02). CONCLUSIONS: These results indicate that decreases in TMB and targeted neoantigens partially account for the difference in response to ACT and that additional factors likely influence responses in these patients. See related commentary by Blass and Ott, p. 2980.

Development and initial psychometric properties of the Cannabidiol Outcome Expectancies Questionnaire (CBD-OEQ).

Cannabidiol (CBD), a nonpsychoactive cannabinoid, is used by many individuals to treat medical and mental health conditions, despite limited support for the efficacy of CBD for these conditions. Identification of CBD-related outcome expectancies (i.e., beliefs concerning the anticipated effects of CBD) could be useful in understanding the etiology and maintenance of CBD use and/or be useful in administration or clinical trial research. Although there are several measures of cannabis outcome expectancies, cannabis comprises several active compounds (e.g., tetrahydrocannabinol [THC], CBD). Thus, cannabis outcome expectancies may not reflect CBD-specific outcome expectancies. Yet, no known CBD-specific outcome expectancy measure exists. The present study used a three-phase, mixed-methods approach to develop and test the psychometric properties of the Cannabidiol Outcome Expectancy Questionnaire (CBD-OEQ). The CBD-OEQ assessed endorsement (i.e., how much an individual agrees/disagrees with an expected outcome) and desirability ratings (i.e., how desirable an expected outcome is). The initial item pool was administered to 600 adults who endorsed having heard of or using CBD products. Factor analyses supported a 60-item, six-factor structure. There was an initial support for internal consistency and convergent, discriminant, and incremental validity of the CBD-OEQ subscale scores in the present sample. Desirability ratings explained minimal additional variance in CBD variables for most subscales, but moderated the relationship between endorsement ratings and use behaviors for Global Negative Effects and No Effect subscales. The newly developed CBD-OEQ could be used as both a research and a clinical tool. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Molecular signatures of antitumor neoantigen-reactive T cells from metastatic human cancers.

The accurate identification of antitumor T cell receptors (TCRs) represents a major challenge for the engineering of cell-based cancer immunotherapies. By mapping 55 neoantigen-specific TCR clonotypes (NeoTCRs) from 10 metastatic human tumors to their single-cell transcriptomes, we identified signatures of CD8+ and CD4+ neoantigen-reactive tumor-infiltrating lymphocytes (TILs). Neoantigen-specific TILs exhibited tumor-specific expansion with dysfunctional phenotypes, distinct from blood-emigrant bystanders and regulatory TILs. Prospective prediction and testing of 73 NeoTCR signature-derived clonotypes demonstrated that half of the tested TCRs recognized tumor antigens or autologous tumors. NeoTCR signatures identified TCRs that target driver neoantigens and nonmutated viral or tumor-associated antigens, suggesting a common metastatic TIL exhaustion program. NeoTCR signatures delineate the landscape of TILs across metastatic tumors, enabling successful TCR prediction based purely on TIL transcriptomic states for use in cancer immunotherapy.

The association between hormonal contraceptive use and smoking, negative affect, and cessation attempts in college females.

Exogenous and endogenous female hormones influence nicotine use and cessation, potentially through mechanisms such as anxiety and negative affect. In the present study, college females using all types of hormonal contraceptives (HC) were compared to those not using HC to determine the potential influence on current smoking, negative affect, and current and past cessation attempts. Differences between progestin-only and combination HC were also examined. Of the 1,431 participants, 53.2% (n = 761) reported current HC use, and 12.3% (n = 176) of participants endorsed current smoking. Women currently using HC were significantly more likely to smoke (13.5%; n = 103) compared to women not using HC (10.9%; n = 73), p = .04. There was a significant main effect of HC use being associated with lower anxiety levels (p = .005), as well as a significant HC use by smoking status interaction, such that women who smoke using HC reported the lowest levels of anxiety among participants (p = .01). Participants using HC were more likely to be making a current attempt to quit smoking than those not using HC (p = .04) and were more likely to have made past quit attempts (p = .04). No significant differences were observed across women using progestin-only, combined estrogen and progestin, and women not using HC. These findings provide evidence that exogenous hormones may be an advantageous treatment target and that they warrant additional study.

A machine learning model for ranking candidate HLA class I neoantigens based on known neoepitopes from multiple human tumor types.

Tumor neoepitopes presented by major histocompatibility complex (MHC) class I are recognized by tumor-infiltrating lymphocytes (TIL) and are targeted by adoptive T-cell therapies. Identifying which mutant neoepitopes from tumor cells are capable of recognition by T cells can assist in the development of tumor-specific, cell-based therapies and can shed light on antitumor responses. Here, we generate a ranking algorithm for class I candidate neoepitopes by using next-generation sequencing data and a dataset of 185 neoepitopes that are recognized by HLA class I-restricted TIL from individuals with metastatic cancer. Random forest model analysis showed that the inclusion of multiple factors impacting epitope presentation and recognition increased output sensitivity and specificity compared to the use of predicted HLA binding alone. The ranking score output provides a set of class I candidate neoantigens that may serve as therapeutic targets and provides a tool to facilitate in vitro and in vivo studies aimed at the development of more effective immunotherapies.

Impact of Prior Treatment on the Efficacy of Adoptive Transfer of Tumor-Infiltrating Lymphocytes in Patients with Metastatic Melanoma.

PURPOSE: Adoptive cell transfer (ACT) of autologous tumor-infiltrating lymphocytes (TIL) can mediate durable responses in patients with metastatic melanoma. This retrospective analysis provides long-term follow-up and describes the effect of prior therapy on outcomes after ACT-TIL. PATIENTS AND METHODS: Patients with metastatic melanoma underwent surgical resection of a tumor for generation of TILs and were treated with a lymphodepleting preparative regimen followed by adoptive transfer of TILs and intravenous IL2. Clinical characteristics of enrolled patients and treatment characteristics of TIL infusion products over two decades of ACT were analyzed to identify predictors of objective response. RESULTS: Adoptive transfer of TILs mediated an objective response rate of 56% (108/192) and median melanoma-specific survival of 28.5 months in patients naïve to anti-programmed cell death-1 (PD-1) therapy compared with 24% (8/34) and 11.6 months in patients refractory to anti-PD-1 (aPD-1). Among patients with BRAF V600E/K-mutated disease, prior treatment with targeted molecular therapy was also associated with a decreased response rate (21% vs. 60%) and decreased survival (9.3 vs. 50.7 months) when compared with those patients naïve to targeted therapy. With a median potential follow-up of 89 months, 46 of 48 complete responders in the aPD-1-naïve cohort have ongoing responses after a single treatment and 10-year melanoma-specific survival of 96%. CONCLUSIONS: Patients previously treated with PD-1 or MAPK inhibition are significantly less likely to develop durable objective responses to ACT-TIL. While ACT-TIL is currently being investigated for treatment-refractory patients, it should also be considered as an initial treatment option for eligible patients with metastatic melanoma. See related commentary by Sznol, p. 5156.

Identification and Validation of T-cell Receptors Targeting RAS Hotspot Mutations in Human Cancers for Use in Cell-based Immunotherapy.

PURPOSE: Immunotherapies mediate the regression of human tumors through recognition of tumor antigens by immune cells that trigger an immune response. Mutations in the RAS oncogenes occur in about 30% of all patients with cancer. These mutations play an important role in both tumor establishment and survival and are commonly found in hotspots. Discovering T-cell receptors (TCR) that recognize shared mutated RAS antigens presented on MHC class I and class II molecules are thus promising reagents for "off-the-shelf" adoptive cell therapies (ACT) following insertion of the TCRs into lymphocytes. EXPERIMENTAL DESIGN: In this ongoing work, we screened for RAS antigen recognition in tumor-infiltrating lymphocytes (TIL) or by in vitro stimulation of peripheral blood lymphocytes (PBL). TCRs recognizing mutated RAS were identified from the reactive T cells. The TCRs were then reconstructed and virally transduced into PBLs and tested. RESULTS: Here, we detect and report multiple novel TCR sequences that recognize nonsynonymous mutant RAS hotspot mutations with high avidity and specificity and identify the specific class-I and -II MHC restriction elements involved in the recognition of mutant RAS. CONCLUSIONS: The TCR library directed against RAS hotspot mutations described here recognize RAS mutations found in about 45% of the Caucasian population and about 60% of the Asian population and represent promising reagents for "off-the-shelf" ACTs.

Contralateral Suppression Index Does Not Predict Clinical Cure in Patients Undergoing Surgery for Primary Aldosteronism.

BACKGROUND: Adrenal venous sampling (AVS) is recommended before adrenalectomy for patients with primary aldosteronism (PA) over 35 years old. The literature examining contralateral suppression (CoS) on AVS in predicting surgical outcomes is conflicting. We examined the presence of CoS in patients who underwent adrenalectomy while adjusting for clinical and biochemical factors associated with a clinical cure of hypertension (ccHTN). METHODS: We performed a retrospective review of patients with successful AVS who underwent unilateral adrenalectomy for PA at a quaternary referral center. Patients were excluded if they had overt cortisol co-secretion, or inadequate follow-up. We first evaluated the aldosterone resolution score (ARS) in predicting ccHTN in our cohort. Next, the receiver-operator characteristic analysis (ROC) was used to determine the optimal contralateral suppression index (CSI) cutoff to define CoS. We performed univariable and multivariable analyses of factors associated with ccHTN. The primary outcome was ccHTN defined as blood pressure less than 140/90 mmHg, and off blood pressure medications. RESULTS: Of the 102 patients on bivariable analysis, age, sex, duration of HTN, number of medications, preoperative systolic blood pressure, and creatinine level were associated with ccHTN. ROC analysis of ARS had an AUC of 0.850 (p < 0.001). On multivariable analysis, only ARS remained associated with ccHTN (OR 3.40, 95% CI 1.20-9.61, p = 0.021). CSI was not significantly associated with ccHTN on ROC, bivariable, or multivariable analyses. CONCLUSION: The presence of CoS was not useful in predicting ccHTN following unilateral adrenalectomy for PA in our cohort. After adjusting for clinical and biochemical factors, ARS remains a useful predictor for ccHTN.

Protective behavioral strategies underutilization mediates effect of a brief motivational intervention among socially anxious undergraduate drinkers.

Social anxiety (SA) is implicated in problematic undergraduate drinking. Brief motivational interventions (BMIs) reduce problematic undergraduate drinking. However, not all students benefit. Identification of vulnerable subgroups is an important next step. The current study examined the role of SA and protective behavioral strategies (PBS) on BMI outcomes. We reanalyzed a subset of data (53.3%; N = 120; 62.5% male) from a randomized trial in which heavy drinking undergraduates were randomized to a BMI or control. SA, past-month typical drinks, peak drinks, weekly quantity, alcohol problems, and PBS were assessed at baseline and 6 weeks. Main effects and interaction among the intervention condition (BMI vs. control) and SA group (low vs. high) were tested on alcohol outcomes and PBS. High SA undergraduates reported greater baseline drinking, more alcohol problems, and lower PBS. Post-BMI, high SA drinkers continued to report greater peak drinks, typical drinks, alcohol problems, and lower PBS use, controlling for baseline use. Among the BMI condition, parallel multiple mediation analyses revealed the PBS subscale Manner of Drinking uniquely mediated the relationship between SA and heavier post-BMI drinking. The PBS Manner of Drinking and Serious Harm Reduction subscales jointly mediated the relationship between SA and greater post-BMI alcohol problems. BMIs may need to be refined to improve outcomes for socially anxious drinkers. Increasing PBS utilization post-BMI may help improve BMI efficacy in this vulnerable group. Clinical implications are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Smoking and suicidal ideation among college students: Smoking expectancies as potential moderators.

Objective: In the present study, we sought to establish a link between suicidal ideation (SI) and smoking in college students, determine whether psychopathology accounted for the association, and determine whether smoking expectancies were moderators. Participants: Participants (N = 607) were identified as nonsmokers, exsmokers, infrequent smokers, or daily smokers. Methods: Participants were assessed for smoking patterns, smoking expectancies, psychopathology, SI, and past suicide attempts. Results: Daily smokers had the highest level of SI. There was a dose-response relationship between smoking and SI, such that the higher the daily smoking rate, the greater the SI, even when controlling for depression, alcohol use, and drug use. Trend-level results indicated that at lower smoking rates, elevated smoking-related negative affect reduction (NAR) expectancies were associated with lower SI, while elevated NAR expectancies in combination with higher smoking rates were associated with greater SI. Conclusion: Smoking cessation programs for college students should screen for SI.

Evaluation of Factors Associated With Successful Matriculation to Colon and Rectal Surgery Fellowship.

BACKGROUND: As an increasing number of general surgery residents apply for fellowship positions, it is important to identify factors associated with successful matriculation. For applicants to colon and rectal surgery, there are currently no objective data available to distinguish which applicant attributes lead to successful matriculation. OBJECTIVE: The purpose of this study was to identify objective factors that differentiate colon and rectal surgery fellowship applicants who successfully matriculate with those who apply but do not matriculate. DESIGN: This was a retrospective analysis of colon and rectal surgery applicant characteristics. SETTINGS: Deidentified applicant data provided by the Association of American Medical Colleges from 2015 to 2017 were included. MAIN OUTCOME MEASURES: Applicant demographics, medical school and residency factors, number of program applications, number of publications, and journal impact factors were analyzed to determine associations with successful matriculation. RESULTS: Most applicants (n = 371) and subsequent matriculants (n = 248) were white (61%, 62%), male (65%, 63%), US citizens (80%, 88%) who graduated from US allopathic medical schools (66%, 75%). Statistically significant associations included graduation from US allopathic medical schools (p < 0.0001), US citizenship (p < 0.0001), and number of program applications (p = 0.0004). Other factors analyzed included American Osteopathic Association membership (p = 0.57), university-based residency (p = 0.51), and residency association with a colon and rectal surgery training program (p = 0.89). Number of publications and journal impact factors were not statistically different between cohorts (p = 0.067, p = 0.150). LIMITATIONS: American Board of Surgery In-Training Examination scores, rank list, and subjective characteristics, such as strength of interview and letters of recommendation, were not available using our data source. CONCLUSIONS: Successful matriculation to a colon and rectal surgery fellowship program was found to be associated with US citizenship, graduation from a US allopathic medical school, and greater number of program applications. The remaining objective metrics analyzed were not associated with successful matriculation. Subjective and objective factors that were unable to be measured by this study are likely to play a determining role. See Video Abstract at http://links.lww.com/DCR/B415. EVALUACIN DE FACTORES VINCULADOS EN LA INMATRICULACIN EXITOSA PARA BECAS DE CIRUGA COLORRECTAL: ANTECEDENTES:A medida que un número cada vez mayor de residentes de Cirugía General solicitan una beca, es importante identificar los factores vinculados con una inmatriculación exitosa. Para los candidatos a una beca en Cirugía Colorrectal, hoy en día no existen datos objetivos disponibles para distinguir qué atributos del solicitante conducen a una inmatriculación exitosa.OBJETIVO:Identificar objetivamente los factores que diferencian un candidato a una beca en Cirugía Colorrectal que se inmatricula con éxito de aquel que aplica pero no llega a inmatricularse.DISEÑO:Análisis retrospectivo de las características de los solicitantes de beca para Cirugía Colorrecatl.AJUSTES:Datos de los solicitantes no identificados, proporcionados por la Asociación de Colegios Médicos Estadounidenses de 2015 a 2017.PRINCIPALES MEDIDAS DE RESULTADO:Se analizaron los factores demográficos del solicitante, las facultades de medicina y los factores de la residencia, el número de solicitudes de programas, el número y el factor de impacto de las publicaciones realizadas para determinar la asociación con una inmatriculación exitosa.RESULTADOS:La mayoría de los solicitantes (n = 371) que posteriormente fueron inmatriculados exitosamente (n = 248) eran blancos (61%, 62%, respectivamente), hombres (65%, 63%), ciudadanos estadounidenses (80%, 88%) que se graduaron de Facultades de medicina alopática en los EE. UU. (66%, 75%). Las asociaciones estadísticamente significativas incluyeron la graduación de las escuelas de medicina alopática de los EE. UU. (P <0,0001), la ciudadanía de los EE. UU. (P <0,0001) y el número de solicitudes de programas (p = 0,0004). Otros factores analizados incluyeron: membresía AOA (p = 0,57), la residencia universitaria (p = 0,51) y asociación de la residencia con un programa de formación en Cirugía Colorrectal (p = 0,89). El número de publicaciones y los factores de impacto de las revistas no fueron estadísticamente diferentes entre las cohortes (p = 0,067, p = 0,15, respectivamente).LIMITACIONES:El Score ABSITE, la posición en lista de clasificación y las características subjetivas como el de una buena entrevista y las cartas de recomendación no se encontraban disponibles en la fuente de datos.CONCLUSIONES:Se encontró que la inmatriculación exitosa a un programa de becas de Cirugía Colorreectal estaba asociada con la ciudadanía estadounidense, la graduación en una Facultad de medicina alopática en los EE. UU, y al mayor número de solicitudes de programas. El analisis de las medidas objetivas restantes no se asociaron con una inmatriculación exitosa. Es probable que los factores subjetivos y objetivos que no pudieron ser medidos por este estudio jueguen un papel determinante. Consulte Video Resumen en http://links.lww.com/DCR/B415. (Traducción-Dr Xavier Delgadillo).

Pancreatic insufficiency following pancreatectomy: Does underlying tumor syndrome confer a greater risk?

BACKGROUND: The risk of postoperative pancreatic exocrine insufficiency (PPEI) is unknown in patients with multiple endocrine neoplasia type I (MEN1) and von Hippel-Lindau (VHL) who require resection of pancreatic neuroendocrine tumors (PNETs). METHODS: A retrospective review of patients who underwent resection of PNETs at the National Institutes of Health from 2007 to 2019 was performed. RESULTS: Our cohort included 82 patients (VHL n = 25, MEN1 n = 20, sporadic n = 37), 6 of whom developed PPEI. While VHL compared to all non-VHL patients (p = 0.046), non-functional PNETs (p = 0.050), and pancreaticoduodenectomy (PD) (p=<0.001) were associated with higher rates of PPEI on univariate analysis, only PD was found to be an independent predictor of PPEI on multivariate analysis (OR 14.43, 95% CI 1.43-145.8, p = 0.024). CONCLUSIONS: The rate of PPEI in patients with hereditary tumor syndromes was similar to that of sporadic PNETs. PD was independently associated with PPEI, and this increased risk should be included in preoperative counseling.

Stem-like CD8 T cells mediate response of adoptive cell immunotherapy against human cancer.

Adoptive T cell therapy (ACT) using ex vivo-expanded autologous tumor-infiltrating lymphocytes (TILs) can mediate complete regression of certain human cancers. The impact of TIL phenotypes on clinical success of TIL-ACT is currently unclear. Using high-dimensional analysis of human ACT products, we identified a memory-progenitor CD39-negative stem-like phenotype (CD39-CD69-) associated with complete cancer regression and TIL persistence and a terminally differentiated CD39-positive state (CD39+CD69+) associated with poor TIL persistence. Most antitumor neoantigen-reactive TILs were found in the differentiated CD39+ state. However, ACT responders retained a pool of CD39- stem-like neoantigen-specific TILs that was lacking in ACT nonresponders. Tumor-reactive stem-like TILs were capable of self-renewal, expansion, persistence, and superior antitumor response in vivo. These data suggest that TIL subsets mediating ACT response are distinct from TIL subsets enriched for antitumor reactivity.