Citations

The present study examines connections between patient expectations and health-related quality of life. We explore a key distinction between expectations about general health and expectations for functional improvement. Patients were 1444 individuals with multiple conditions experiencing chronic pain who were seeking treatment at the Gastein Healing Gallery in Böckstein, near Bad Gastein, Austria. In addition to measures of expectations, patients completed measures of pain, mental and physical health, life satisfaction, fatigue, and sleep problems. Structural equation models were used to fit a latent variable model where both expectation variables were used to predict health-related quality of life. Results showed that expectations regarding potential functional improvement resulting from treatments at the Gastein Healing Gallery were associated with improved health-related quality of life. Expectations about general health improvements related to treatment were not associated with health-related quality of life. To facilitate optimal healing, clinicians may decide to emphasize expectations about functional recovery when discussing treatment methods similar to those offered at the Gastein Healing Gallery, and in so doing, health-related quality of life may benefit.

Abstract Introduction: Muscle-Invasive Bladder Cancer (MIBC) is associated with a poor overall survival rate. One important factor that contributes to poor treatment outcomes is the histologic heterogeneity of MIBC tumors, which limits the translational value of some rodent models. As opposed to mice, dogs with spontaneously occurring bladder cancer have been shown to present with similar clinical behavior as human MIBC. In addition, canines have an intact immune system, which could provide for an ideal pre-clinical study population to investigate the efficacy of immunotherapy. In this study, we evaluated canine MIBC tumor biopsies for their similarities to human MIBC with regards to histology and immune cell infiltration. Materials & Methods: Nine canine MIBC tumor samples were provided by the ISU pathology service and evaluated by a human uropathologist. Canine MIBC tumors were phenotypically characterized using either immunofluorescence (IF) or RNA in situ hybridization (RNA-ISH), including CD44, KRT7 and FOXA1, as well as specific markers characterizing the immune cell infiltrate, such as CD163 (tumor-associated macrophages), CD8a (cytotoxic T-lymphocytes), PD-L1 (immune-checkpoint protein) and TGFβ2 (cancer-associated fibroblasts). Results: Histologically, all canine MIBCs were classified as invasive, high-grade urothelial carcinomas (UC) with identical morphology to human MIBC. Interestingly, previously described histological variants of human MIBC tumors were also observed within the canine MIBC samples, such as glandular differentiation in 3/9 canine MIBC samples; epithelial-mesenchymal transition with sarcomatoid differentiation 1/9, squamous differentiation in 2/9 and micropapillary carcinoma in 1/9, all of which have been associated with poor clinical outcomes in human patients. IF was strongly positive for KRT7, FOXA1 and CD44, and immune cell markers CD163 and TGFβ2. However, CD8a was only weakly expressed (5/9) or negative, and PD-L1 was only positive in 4/9 canine MIBC biopsies. Conclusions: Canine MIBC tumors showed significant heterogeneity with highly similar histological variant morphologies to those reported in humans with MIBC. Furthermore, phenotypic characterization of immune cell infiltrates and checkpoint proteins suggest that the tumors were typically immunologically “cold”. These data further establish the utility of the spontaneous canine model of MIBC for pre-clinical investigation of novel therapeutic drug candidates, including immunotherapies. Citation Format: Karin Allenspach, John Cheville, Hannah Wickham, Christopher Zdyrski, Vojtech Gabriel, Basant Ahmed, Mei-Jyun Ciou, Fabrice Lucien, Igor Frank, Olufemi Fasina, Pablo Pineyro, Johnathan P. Mochel. Similar variant histology and immune cell infiltration in canine and human muscle-invasive bladder cancer [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 2509.

Anticoagulant-related nephropathy (ARN) is a rare, newly recognized cause of acute kidney injury and significant but underdiagnosed complication of anticoagulation therapy. ARN occurs in patients taking oral anticoagulant therapy most often warfarin or a novel oral anticoagulant (NOAC). It is a potentially devastating disorder with serious renal consequences and increased all-cause mortality. Anticoagulant-related nephropathy presents as an acute kidney injury (AKI) in the setting of a supratherapeutic INR with profuse glomerular hemorrhage seen as renal tubules filled with red cells and red cell casts on renal biopsy. Being that millions of Americans are on warfarin, a thorough understanding and awareness of the clinical presentation, diagnosis, and therapeutic interventions are crucial to protecting the renal function, lowering all-cause mortality and optimizing treatment. Our goal is to provide education on a newly recognized form of AKI and significant but underdiagnosed complication of anticoagulation therapy.

Abstract Palliative care (PC) benefits patients undergoing hematopoietic stem cell transplantation (HSCT), but it remains underutilized. Although transplant physicians report concerns regarding how patients perceive PC, HSCT recipients’ perceptions about PC remain unaddressed. We conducted a multisite, cross-sectional survey of autologous and allogeneic HSCT recipients 3 to 12 months after transplant to assess their familiarity, knowledge, and perception of PC, as well as their unmet PC needs. We computed a composite score of patients’ perceptions of PC and used a generalized linear regression model to examine factors associated with these perceptions. We enrolled 69.6% (250/359) of potential participants (median age = 58.1; 63.1% autologous HSCT). Overall, 44.3.8% (109/249) reported limited knowledge about PC and 52% (127/245) endorsed familiarity with PC. Most patients felt hopeful (54%) and reassured (50%) when they heard the term PC; 83% saw referral as a sign their doctor cared about what was happening to them. In multivariate analyses, patients who were more knowledgeable about PC were more likely to have positive perceptions of PC (B = 7.54, standard error = 1.61, P < .001). Patients’ demographics, HSCT features, quality of life, and symptom burden were not significantly associated with perceptions of PC. HSCT recipients have positive perceptions of PC, though many have limited knowledge about its role. Patients who were more knowledgeable about PC were more likely to have positive perceptions of PC. These data do not support transplant physicians’ negative concerns about how patients perceive PC and underscore the need to further educate patients and transplant physicians about PC.

Abstract Breast parenchymal patterns on radiologic images are associated with breast cancer risk. Radiomic features have been proposed as quantitative measures of parenchymal patterns. We defined intrinsic imaging phenotypes of breast parenchymal patterns based on radiomic features extracted from full field digital mammography (FFDM) in breast screening populations and assessed whether these phenotypes are associated with breast cancer risk and masking. We selected 30,000 women with 4-view FFDM exams from Hologic machines from three institutions (Hospital of the University of Pennsylvania, Mayo Clinic, and San Francisco Mammography Registry), randomly split into a training (20,000 women) and test set (10,000 women). In total, 390 radiomic features were automatically extracted from each image using a validated software pipeline, standardized, and adjusted for site differences using ComBat. We used two methods, hierarchical clustering and Principal Components (PCs) analysis, to classify significant variation among the features in the training set and replicate among the test set. Next, we applied the replicated clusters and PCs to an independent nested case-control set [1082 invasive breast cancer (BC) cases (of which 151 were Black and 893 White women, 38 other race) matched to 2837 controls (411 Black and 2345 White women, 81 other race) on age, race, timing of images, and site]. We examined associations of the clusters and PCs with invasive breast cancer risk, as well as masking [defined as a false-negative (FN) screen (124 cases and 319 matched controls) and additionally the subset with symptomatic interval cancer (IC) within 12 months of negative screen (88 cases and 223 matched controls)] using conditional logistic regression. We evaluated their association with breast cancer alone, and with adjustment for age, body mass index (BMI) and breast density assessed by Breast Imaging Reporting and Data System (BI-RADS) using likelihood ratio tests. We estimated discrimination using area under the curve (AUC) and compared AUCs for models that included the radiomic clusters and PCs with the model that included only age, BMI and density. We also stratified analyses by race (Black/White). From hierarchical clustering, we defined six statistically significant phenotype clusters (each of at least 1000 women) in the training set which were replicated in the test set. For PC Analysis, we identified six PCs in the training set, explaining 85% of the variation in texture features and reproduced these in the test set. The six radiomic phenotype clusters (P< 0.001) and six PCs (P< 0.001) were both associated with invasive BC, including after adjusting for age, BMI, and density (cluster P=0.004; PCs P< 0.001). Improvements in discrimination of invasive BC with inclusion of PCs or clusters were more pronounced among Black women (Table). Further, the PCs (P< 0.001) and clusters (P< 0.001) were significantly associated with FN overall and for symptomatic IC (PCs P< 0.001; clusters P=0.001), but only PCs remained significant after adjusting for age, BMI and density (PCs P=0.004 for FN; PCs P=0.007 for symptomatic IC). Discrimination of masking also improved with inclusion of both clusters and PCs (Table). We identified reproducible radiomic phenotypes that are associated with invasive BC risk, above and beyond breast density with the strongest associations for invasive BC among Black women and symptomatic interval cancers. Citation Format: Stacey Winham, Anne Marie McCarthy, Aimilia Gastounioti, Christopher Scott, Aaron Norman, Walter C. Mankowski, Lauren Pantalone, Matthew Jensen, Eric A. Cohen, Hannah Horng, Kathleen Brandt, Emily F. Conant, Karla Kerlikowske, Despina Kontos, Celine Vachon. Radiomic phenotypes of breast texture and association with breast cancer risk and masking [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS4-06.

OBJECTIVES: To assess the wholistic costs of systemic anticoagulation delivery in heparin versus bivalirudin-based maintenance of adult patients supported on extracorporeal membrane oxygenation (ECMO). DESIGN: Single-center retrospective cohort study. SETTING: Large academic ECMO center. PATIENTS: Adults on ECMO receiving heparin or bivalirudin for primary maintenance systemic anticoagulation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Electronic data were abstracted from a database maintained by our ECMO center, which transitioned to a preferred bivalirudin-based anticoagulation management in 2017. The pretransition group consisted of 126 patients (123 heparin and three bivalirudin), whereas the posttransition group included 275 patients (82 heparin and 193 bivalirudin). Drug costs were estimated using the wholesale acquisition cost, and laboratory assays costs were estimated using reimbursement fee schedules. Cost data were normalized to the duration of the ECMO run and reported in U.S. Dollar per ECMO day. Following the practice change, bivalirudin patients were less likely to receive AT supplementation (31.0 vs 12.4%; p < 0.0001) and had fewer coagulation assays ordered (6.1 vs 5.4 per ECMO day; p = 0.0004). After the transition, there was a dramatic decrease in costs related to AT assay assessments ($11.78 [interquartile range {IQR}, $9.48–$13.09] vs $1.03 [IQR, $0–$5.75]; p < 0.0001) and AT supplementation ($0 [IQR, $0–$312.82] vs $0 [IQR, $0–$0]; p < 0.0001) per ECMO day. Unadjusted survival at 28 days was higher posttransition (64.3 vs 74.9%; p = 0.0286). CONCLUSIONS: Antithrombin assays and supplementation compromise a significant proportion of heparin-based anticoagulation costs in ECMO patients and is substantially reduced when a bivalirudin-based anticoagulation strategy is deployed. A favorable association exists between the aggregate cost of administration of bivalirudin compared with heparin-based systemic anticoagulation in adults supported on ECMO driven by reductions in antithrombin activity assessments and the cost of antithrombin replacement.

BACKGROUND Iatrogenic aortic injury from pedicle screw malpositioning or anterior prominence in posterior spinal fusion represents a rare but potentially devasting complication. While intraoperative aortic injury is associated with hemodynamic instability, delayed presentations of pedicle screw aortic impingement or violation often present insidiously with pseudoaneurysm or vascular remodeling in clinically asymptomatic patients. Currently, there is a lack of guidance in the field for the recommended surveillance, urgency of operative intervention, and optimal surgical management of delayed pedicle screw aortic injuries. OBSERVATIONS The following case study discusses the open treatment of delayed thoracic aortic penetration from an excessively long T12 pedicle screw in an asymptomatic adolescent patient with idiopathic scoliosis. The pedicle screw prominence anteriorly was corrected by burring the screw tip until it was flush with the vertebral body. The associated aortic injury was addressed with open vascular repair via primary anastomosis supplemented with a bovine pericardial patch. LESSONS Complete aortic wall penetration from an excessively long thoracic pedicle screw with otherwise stable screw positioning may be addressed most effectively with a single anterior surgical approach for open aortic repair and screw tip burring.

AbstractBackgroundHospital medicine (HM) has a well‐described gender disparity related to academic work and promotion. During the COVID‐19 pandemic, female authorship across medicine fell further behind historical averages.ObjectiveExamine how COVID‐19 affected the publication gender gap for hospitalists.Design, Settings, and ParticipantsBibliometric analysis to determine gender and specialty of US‐based physician first and last authors of COVID‐19 articles published March 1, 2020 to February 28, 2021 in the four highest impact general medical journals and two highest impact HM‐specific journals.Main Outcome and MeasuresWe characterized the percentage of all physician authors that were women, the percentage of physician authors that were hospitalists, and the percentage of HM authors that were women. We compared author gender between general medical and HM‐specific journals.ResultsDuring the study period, 853 manuscripts with US‐based first or last authors were published in eligible journals. Included manuscripts contained 1124 US‐based physician first or last author credits, of which 34.2% (384) were women and 8.8% (99) were hospitalists. Among hospitalist author credits, 43.4% (n = 43/99) were occupied by women. The relative gender equity for hospitalist authors was driven by the two HM journals where, compared to the four general medical journals, hospitalist authors (54.1% [33/61] vs. 26.3% [10/38] women, respectively, p = .002) and hospitalist last authors (51.9% [14/27] vs. 20% [4/20], p = .03) were more likely to be women.ConclusionsAcross COVID‐19‐related manuscripts, disparities by gender were driven by the high‐impact general medical journals. HM‐specific journals had more equitable inclusion of women authors, demonstrating the potential impact of proactive editorial policies on diversity.

Background: Epidemiological studies of lateral ankle sprains in NCAA sports are important in appraising the burden of this injury and informing prevention efforts. Purpose: To describe the epidemiology of lateral ankle sprains in NCAA sports during the 2014-15 through 2018-19 seasons. Study Design: Descriptive epidemiology study. Methods: Injury and exposure information collected within the NCAA Injury Surveillance Program (ISP) were examined. Counts, rates, and proportions of lateral ankle sprains were used to describe injury incidence by sport, event type (practices, competitions), season segment (preseason, regular season, postseason), injury mechanism (player contact, noncontact, and surface contact, injury history (new, recurrent), and time loss (time loss [≥1 day], non–time loss). Injury rate ratios (IRRs) were used to examine differential injury rates, and injury proportion ratios (IPRs) were used to examine differential distributions. Results: A total of 3910 lateral ankle sprains were reported (4.61 per 10,000 athlete exposures) during the study period, and the overall rate was highest in men’s basketball (11.82 per 10,000 athlete exposures). The competition-related injury rate was higher than the practice-related rate (IRR, 3.24; 95% CI, 3.04-3.45), and across season segments, the overall rate was highest in preseason (4.99 per 10,000 athlete exposures). Lateral ankle sprains were most often attributed to player-contact mechanisms in men’s (43.2%) and women’s sports (35.1%), although injuries were more prevalently attributed to player contact in men’s than in women’s sports (IPR, 1.23; 95% CI, 1.13-1.34). Overall, 49.7% of all lateral ankle sprains were time loss injuries. Conclusions: The findings of this study are consistent with previous epidemiological investigations of lateral ankle sprains among NCAA athletes. Results offer additional context on differential injury mechanisms between men’s and women’s sports and on injury risk across the competitive season. Future research may examine the effectiveness of deploying injury prevention programs before the start of a season.