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The development of vascular access for hemodialysis has come a long way since 1943 when the first hemodialysis treatment was performed in humans by connecting an artery and vein using an external glass canula. Since then, vascular access care has evolved robustly through contributions from numerous countries and professional nephrology societies, worldwide. To understand the global distribution and contribution of different specialties to medical literature on dialysis vascular access care, we performed a literature search from 1991 to 2021 and identified 2768 articles from 74 countries. The majority of publications originated from the United States (41.5%), followed by China (5.1%) and the United Kingdom (4.6%). Our search results comprise of observational studies (43%), case reports/series (27%), review articles (16.5%) and clinical trials (12%). A large proportion of articles were published in Nephrology journals (49%), followed by General Medicine (14%), Surgery (10%), Vascular Medicine (8%), and Interventional Radiology journals (4%). With the introduction of interventional nephrology, nephrologists will be able to assume the majority of the responsibility for dialysis vascular access care and above all maintain a close interdisciplinary collaboration with other specialties to provide optimum patient care. In this review article, we discuss the history, evolving knowledge, challenges, educational opportunities, and future directions of dialysis vascular access care, worldwide.

BACKGROUND: A racial compensation disparity among physicians across numerous specialties is well documented and persists after adjustment for age, sex, experience, work hours, productivity, academic rank, and practice structure. This study examined national survey data to determine whether there are racial differences in compensation among anesthesiologists in the United States. METHODS: In 2018, 28,812 active members of the American Society of Anesthesiologists were surveyed to examine compensation among members. Compensation was defined as the amount reported as direct compensation on a W-2, 1099, or K-1, plus all voluntary salary reductions (eg, 401[k], health insurance). Covariates potentially associated with compensation were identified (eg, sex and academic rank) and included in regression models. Racial differences in outcome and model variables were assessed via Wilcoxon rank sum tests and Pearson’s χ 2 tests. Covariate adjusted ordinal logistic regression estimated an odds ratio (OR) for the relationship between race and ethnicity and compensation while adjusting for provider and practice characteristics. RESULTS: The final analytical sample consisted of 1952 anesthesiologists (78% non-Hispanic White). The analytic sample represented a higher percentage of White, female, and younger physicians compared to the demographic makeup of anesthesiologists in the United States. When comparing non-Hispanic White anesthesiologists with anesthesiologists from other racial and ethnic minority groups, (ie, American Indian/Alaska Native, Asian, Black, Hispanic, and Native Hawaiian/Pacific Islander), the dependent variable (compensation range) and 6 of the covariates (sex, age, spousal work status, region, practice type, and completed fellowship) had significant differences. In the adjusted model, anesthesiologists from racial and ethnic minority populations had 26% lower odds of being in a higher compensation range compared to White anesthesiologists (OR, 0.74; 95% confidence interval [CI], 0.61–0.91). CONCLUSIONS: Compensation for anesthesiologists showed a significant pay disparity associated with race and ethnicity even after adjusting for provider and practice characteristics. Our study raises concerns that processes, policies, or biases (either implicit or explicit) persist and may impact compensation for anesthesiologists from racial and ethnic minority populations. This disparity in compensation requires actionable solutions and calls for future studies that investigate contributing factors and to validate our findings given the low response rate.

Introduction Arteriovenous fistulas at the craniocervical junction (CCAVFs) are challenging to treat due to variation in angioarchitecture and shunting sites. No consensus exists as to whether open surgery or endovascular approaches are better in regards to outcomes, complications, and need for reintervention. As such, weexplore the efficacy, outcomes, and complications of endovascular versus open surgery for dural arteriovenous fistulas at the craniocervical junction. Methods A systematic review was performed using the EMBASE, PubMed,and Cochrane databases in April 2022. MeSH search terms included (craniocervical) AND (arteriovenous OR fistula OR AVF). Inclusion criteria were defined as patients with CCAVFs who were treated with open surgery or endovascular therapy with reported clinical outcomes at 6 months or later. Results A total of 357 studies were screened; of which 75 were included. A total of 416 patients (309 males, 91 females) were included with an average age of 61.9 years. A total of 236 patients underwent surgery (mean age: 61.5), 71 patients underwent embolization (mean age: 62.6), and 25 patients underwent a combination (mean age: 54.7). Outcomes were reported in 39 surgery cases (mean follow up time: 31.4 months), and 54 endovascular cases (mean follow up time: 24.2 months). Within the open surgery group 47 (57.3%) had complete symptom resolution, 23 (28%) had symptom improvement or stabilization, 11 (13.4%) permanent deficit, and 1 (1.2%) resulted in death. Within the endovascular group 26 (56.5%) had complete symptom resolution, 5 (10.9%) had symptom improvement or stabilization, 15 (32.6%) permanent deficit, and 0 (0%) resulted in death. Conclusions Open surgery and embolization yield comparable symptomatic improvement and stabilization. However, the rate of permanent deficits is higher withembolization, while mortality is higher with open surgery. Further studies are required to better associate these outcomes to baseline parameters including treatment decision making, size of the lesion, patient age, and co‐morbidities.

Abstract Background Large β-globin gene cluster deletions (hereditary persistence of fetal hemoglobin [Hb] or β-, δβ-, γδβ-, and ϵγδβ-thalassemia), are associated with widely disparate phenotypes, including variable degrees of microcytic anemia and Hb F levels. When present, increased Hb A2 is used as a surrogate marker for β-thalassemia. Notably, ϵγδβ-thalassemias lack the essential regulatory locus control region (LCR) and cause severe transient perinatal anemia but normal newborn screen (NBS) results and Hb A2 levels. Herein, we report a novel deletion of the ϵ, Aγ, Gγ, and ψβ loci with intact LCR, δ-, and β-regions in 2 women and newborn twins. Methods Capillary electrophoresis (CE), high-performance liquid chromatography (HPLC), DNA sequencing, multiplex ligation-dependent probe amplification (MLPA), gap-polymerase chain reaction (gap-PCR), and long-read sequencing (LRS) were performed. Results NBS showed an Hb A > Hb F pattern for both twins. At 20 months, Hb A2 was increased similarly to that in the mother and an unrelated woman. Unexplained microcytosis was absent and the twins lacked severe neonatal anemia. MLPA, LRS, and gap-PCR confirmed a 32 599 base pair deletion of ϵ (HBE1) through ψβ (HBBP1) loci. Conclusions This deletion represents a hemoglobinopathy category with a distinct phenotype that has not been previously described, an ϵγ-thalassemia. Both the NBS Hb A > F pattern and the subsequent increased Hb A2 without microcytosis are unusual. A similar deletion should be considered when this pattern is encountered and appropriate test methods selected for detection. Knowledge of the clinical impact of this new category will improve genetic counselling, with distinction from the severe transient anemia associated with ϵγδβ-thalassemia.

Importance For many types of epithelial malignant neoplasms that are treated with definitive radiotherapy (RT), treatment prolongation and interruptions have an adverse effect on outcomes. Objective To analyze the association between RT duration and outcomes in patients with esophageal cancer who were treated with definitive chemoradiotherapy (CRT). Design, Setting, and Participants This study was an unplanned, post hoc secondary analysis of 3 prospective, multi-institutional phase 3 randomized clinical trials (Radiation Therapy Oncology Group [RTOG] 8501, RTOG 9405, and RTOG 0436) of the National Cancer Institute–sponsored NRG Oncology (formerly the National Surgical Adjuvant Breast and Bowel Project, RTOG, and Gynecologic Oncology Group). Enrolled patients with nonmetastatic esophageal cancer underwent definitive CRT in the trials between 1986 and 2013, with follow-up occurring through 2014. Data analyses were conducted between March 2022 to February 2023. Exposures Treatment groups in the trials used standard-dose RT (50 Gy) and concurrent chemotherapy. Main Outcomes and Measures The outcomes were local-regional failure (LRF), distant failure, disease-free survival (DFS), and overall survival (OS). Multivariable models were used to examine the associations between these outcomes and both RT duration and interruptions. Radiotherapy duration was analyzed as a dichotomized variable using an X-Tile software to choose a cut point and its median value as a cut point, as well as a continuous variable. Results The analysis included 509 patients (median [IQR] age, 64 [57-70] years; 418 males [82%]; and 376 White individuals [74%]). The median (IQR) follow-up was 4.01 (2.93-4.92) years for surviving patients. The median cut point of RT duration was 39 days or less in 271 patients (53%) vs more than 39 days in 238 patients (47%), and the X-Tile software cut point was 45 days or less in 446 patients (88%) vs more than 45 days in 63 patients (12%). Radiotherapy interruptions occurred in 207 patients (41%). Female (vs male) sex and other (vs White) race and ethnicity were associated with longer RT duration and RT interruptions. In the multivariable models, RT duration longer than 45 days was associated with inferior DFS (hazard ratio [HR], 1.34; 95% CI, 1.01-1.77; P = .04). The HR for OS was 1.33, but the results were not statistically significant (95% CI, 0.99-1.77; P = .05). Radiotherapy duration longer than 39 days (vs ≤39 days) was associated with a higher risk of LRF (HR, 1.32; 95% CI, 1.06-1.65; P = .01). As a continuous variable, RT duration (per 1 week increase) was associated with DFS failure (HR, 1.14; 95% CI, 1.01-1.28; P = .03). The HR for LRF 1.13, but the result was not statistically significant (95% CI, 0.99-1.28; P = .07). Conclusions and Relevance Results of this study indicated that in patients with esophageal cancer receiving definitive CRT, prolonged RT duration was associated with inferior outcomes; female patients and those with other (vs White) race and ethnicity were more likely to have longer RT duration and experience RT interruptions. Radiotherapy interruptions should be minimized to optimize outcomes.

Abstract Background: Ovarian endometrioid carcinoma (OEC) is an uncommon, understudied histotype that is distinguished from other histotypes by unique genomic features and high hormone receptor expression. There is growing interest in the biological relevance of subtyping using immunohistochemistry (IHC). Methods: Women with primary invasive OEC diagnosed from 1989 to 2010 were retrospectively identified from the population-based Alberta Cancer Registry, Canada. Pathology slide review and IHC staining for Napsin A, TP53, and WT1 were used to reduce histologic misclassification, resulting in N=166 participants (low-stage N=138, high-stage N=28), excluding those who received neo-adjuvant chemotherapy. The following markers were stained and scored on tissue microarrays: TP53 (normal/abnormal), PMS2/MSH6 (mismatch repair proficient [MMRp]/deficient [MMRd]), PGR (loss/retained), and CTNNB1 (nuclear/cytoplasmic). Using a hierarchical decision tree by stage group (low/high), we categorized tumors as TP53 abnormal, MMRd, PGR loss, nuclear CTNNB1, and no specific immunohistochemical profile (NSIP). Distributions and five-year disease specific survival (DSS) was estimated for each group; hazard ratios (HRs) adjusted for age were estimated using Cox regression with NSIP as referent group. Results: Among low-stage cases, five-year survival was as follows: 80% for TP53 abnormal (N=10, 7%), 87% for MMRd (N=15, 11%), 80% for PGR loss (N=10, 7%), 98% for nuclear CTNNB1 (N=63, 46%), and 95% for NSIP group (N=40, 29%). Overall, IHC group was associated with DSS among low stage cases (LRT p-value=0.006), and the group with nuclear CTNNB1 had a small but statistically significant DSS advantage (HR=0.089, 95% CI 0.011-0.742, p=0.025). TP53 and PGR loss suggested shorter DSS than the referent NSIP group, but not statistically significantly so (HR=1.26 and 3.08, respectively). Among high-stage cases, five-year DSS was as follows: 57% for TP53 abnormal (N=7, 25%), 75% for MMRd (N=8, 29%), 33% for nuclear CTNNB1 (N=3, 11%), and 17% for NSIP (N=10, 36%). There were no high-stage cases in the PGR-loss group. Nuclear CTNNB1 group had a shorter DSS among high-stage cases, but this was not statistically significantly so (HR=1.16, p=0.85). Conclusion: Pending replication in additional datasets, results suggest that OEC cases in nuclear CTNNB1 or NSIP IHC groups may have a favorable prognosis in which de-escalation of therapy can be considered. In addition, abnormal TP53 and loss of PGR may identify a high-risk subset of low-stage OEC. Citation Format: Brooke Jorgensen, Stacey Winham, Julie Cunningham, Sebastian Armasu, Chen Wang, Hunter Atkinson, Bryan McCauley, Linda Kelemen, Martin Koebel, Ellen Goode. Towards a combined immunohistochemistry-based subtyping of ovarian endometrioid carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6499.

Abstract Background: Multiple guideline-recommended colorectal cancer (CRC) screening options have been shown to reduce CRC incidence and mortality among average-risk patients. Yet, CRC screening continues to be underutilized in the US. Provider recommendation has consistently shown to improve screening completion. Our study aimed to delineate the pathways through which provider communication influences CRC screening completion. We tested how provider communication about the "Why” and “How” of mt-sDNA screening contributes to mt-sDNA screening intention through influencing patients’ screening outcome expectancies and perceived behavioral control. Methods: Data came from a behavioral theory-informed survey that we developed to identify psychosocial factors associated with mt-sDNA screening. The survey was administered between 3/22-6/22 by RTI International, with a sample of US adults ages 45-75 who received a valid order for mt-sDNA screening with a shipping date between 5/21-9/21. Participants completed an electronic or paper survey. We measured patients’ reports of providers’ “Why” communication with items on mt-sDNA screening performance, advantages/disadvantages, and cost. Providers’ “How” communication was measured with items on instructions and need for follow-up testing. We tested the proposed relationships using structural equation modeling and tested indirect effects using bootstrapping. Results: A total of 2973 participants completed the survey (response rate: 21.7%). “Why” communication was positively associated with perceived effectiveness of mt-sDNA screening (b = 0.349, p < .001) and negatively associated with CRC worry (b = -0.078, p = .002). “How” communication was positively associated with perceived ease of use (b = 0.392, p < .001) and perceived comfort of mt-sDNA screening (b = 0.138, p < .001). Perceived effectiveness and perceived ease of use were positively associated with intention to complete mt-sDNA screening (b = 0.404, p < .001; b = 0.339, p < .001). “Why” communication contributed to screening intention through influencing perceived effectiveness (b-indirect effect = 0.141, 95% CI: 0.115, 0.177). “How” communication contributed to screening intention through influencing perceived ease of use (b-indirect effect = 0.133, 95% CI: 0.104, 0.172). Conclusions: Improving patients’ beliefs about the effectiveness and ease of use of screening may be one pathway through which provider communication contributes to CRC screening completion. Efforts are needed to develop and implement provider-patient communication strategies and toolkits that are efficacious at fostering patient understanding of the rationale for CRC screening and the effectiveness of available screening options as well as addressing barriers and enhancing patients’ self-efficacy in completing their preferred screening option. Citation Format: Xuan Zhu, Paul Limburg, Linda Squiers, Leah Helmueller, Gabriel Madson, Brian Southwell, Carlye Gates, Shama Alam, Jennifer Laffin, Lila Finney Rutten. Provider communication contributes to colorectal cancer screening intention through improving screening outcome expectancies and perceived behavioral control [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 770.

Abstract Background: Recent studies support that high levels of tumor-infiltrating lymphocytes (TILs) were associated with better prognosis in HPV(+) oropharyngeal squamous cell carcinoma (OPSCC). While these studies provide a potential role for TILs as a prognostic biomarker, the analyses were relied on manual quantification performed by pathologists, resulting in inter-observer variability. Deep Learning (DL)-based whole slide hematoxylin and eosin (H&E) image analyses may overcome these challenges. However, this analysis only provides the presence of cell types without consideration for the functional roles of each cell within the tumor immune microenvironment (TME). In this work, we develop a computational pipeline to integrate paired H&E and immunohistochemistry (IHC) images to functionally characterize TILs and investigate their prognostic utility. Methods: We analyzed 88 patients: 42 stage I, 39 stage II, and 7 stage III. Our data contain both H&E and IHCs examining FoxP3, CD3, PD-L1, CD20, etc. on serial sections of the tissue. In-house DL-based H&E analysis used to identify TILs, tumors, and stroma in each tumor, then performed registration between adjacent H&E and IHC images from the same tissue. The patients were then classified into three basic immune phenotypes: immune inflamed (IN; high TILs in the tumor region), immune excluded (EX; TILs are mostly localized in stroma), and immune desert (ID; few/no TILs) based on TIL enrichment in the TME. To functionally characterize TILs, we quantified protein expression from the adjacent IHCs. For example, we further classified each patient into different subtypes based on enriched protein expression (e.g., FoxP3 high IN, FoxP3 low IN). We used the Kaplan-Meier method and multivariate Cox analysis to evaluate the prognostic value of different subtypes enriched with different proteins to predict disease-free survival (DFS). Results: The IN group with 43 patients was significantly associated with good prognosis. Interestingly, further stratification of the IN subgroup based on Foxp3 quantification on TIL regions (i.e., high FoxP3 IN and low FoxP3 IN) showed that high protein expression of FoxP3 in TILs in the IN subgroup is significantly associated with a better prognosis compared to other immune subgroups (HR, 0.16; p-value, 0.003). Multivariate analysis, including other clinical covariates showed that the immune subtypes associated with high FoxP3 are independently associated with DFS. These results demonstrate that DL-based integrative IHC and H&E image analysis could be used to identify subgroups with distinct clinical outcomes. Furthermore, our results reveal unknown roles for Foxp3 expression in the TILs in HPV(+) OPSCC as a prognostic biomarker, a finding which should be evaluated in a larger cohort. Citation Format: Sumanth Reddy Nakkireddy, Inyeop Jang, Minji Kim, Linda X. Yin, Michael Rivera, Joaquin J. Garcia MD, Kathleen R. Bartemes, David M. Routman, Eric J. Moore, Daniel J. Ma, Kathryn M. Van Abel, Tae Hyun Hwang. Integrative spatial analysis of paired IHC and H&E images identifies Foxp3 enriched tumor-infiltrating lymphocytes associated with disease-free survival in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4638.

PURPOSE Breast-conserving therapy (BCT) is the preferred treatment for unifocal breast cancer (BC). The oncologic safety of BCT for multiple ipsilateral breast cancer (MIBC) has not been demonstrated in a prospective study. ACOSOG Z11102 (Alliance) is a phase II, single-arm, prospective trial designed to evaluate oncologic outcomes in patients undergoing BCT for MIBC. PATIENTS AND METHODS Women age 40 years and older with two to three foci of biopsy-proven cN0-1 BC were eligible. Patients underwent lumpectomies with negative margins followed by whole breast radiation with boost to all lumpectomy beds. The primary end point was cumulative incidence of local recurrence (LR) at 5 years with an a priori rate of clinical acceptability of <8%. RESULTS Among 270 women enrolled between November 2012 and August 2016, there were 204 eligible patients who underwent protocol-directed BCT. The median age was 61 years (range, 40-87 years). At a median follow-up of 66.4 months (range, 1.3-90.6 months), six patients developed LR for an estimated 5-year cumulative incidence of LR of 3.1% (95% CI, 1.3 to 6.4). Patient age, number of sites of preoperative biopsy–proven BC, estrogen receptor status and human epidermal growth factor receptor 2 status, and pathologic T and N categories were not associated with LR risk. Exploratory analysis showed that the 5-year LR rate in patients without preoperative magnetic resonance imaging (MRI; n = 15) was 22.6% compared with 1.7% in patients with a preoperative MRI (n = 189; P = .002). CONCLUSION The Z11102 clinical trial demonstrates that breast-conserving surgery with adjuvant radiation that includes lumpectomy site boosts yields an acceptably low 5-year LR rate for MIBC. This evidence supports BCT as a reasonable surgical option for women with two to three ipsilateral foci, particularly among patients with disease evaluated with preoperative breast MRI.

AbstractOur objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high‐grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi‐institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36–3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11–2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.