Orthopaedic Research of Virginia

Primary sclerosing cholangitis-associated UC (PSC-UC) carries excess colorectal neoplasia despite often mild-appearing endoscopy, implicating persistent microscopic inflammation and microbiota-bile acid (BA) dysfunction. To test whether PSC-UC neoplasia is driven by transferable microbiota-mediated inflammation linked to secondary BA loss. Surveillance colonoscopies (2012-2022) from PSC-UC (n=251) and UC-only (n=8839) were compared for segmental endoscopic/histological activity and dysplasia. We generated multidrug resistance protein 2 (MDR2)-/- × interleukin (IL)-10-/- double-knockout (DKO) mice and used germ-free (GF) derivation, faecal microbiota transplantation (FMT), antibiotic conditioning and cohousing with shotgun metagenomics and liquid chromatography-tandem mass spectrometry BA profiling. PSC-UC showed greater inflammatory activity and a right-shifted dysplasia burden versus UC-only. Under specific-pathogen-free conditions, DKO mice developed early right-predominant colitis and multifocal dysplasia progressing with age. DKO communities were depleted of 7α-dehydroxylation capacity with near absence of deoxycholic and lithocholic acids and no enrichment of canonical bacterial genotoxins. GF DKO mice were protected, whereas live DKO donor FMT reinstated severe colitis and dysplasia; sterile-filtered stool supernatant was inactive. IL-10-/- donor FMT or cohousing attenuated colitis and increased recipient secondary BA, whereas wild-type/MDR2-/- donor transfers were non-colitogenic. In GF DKO mice, direct deoxycholic acid repletion caused hepatotoxicity. PSC-UC neoplasia associates with transmissible microbiota-dependent inflammation and secondary BA deficiency. Controlled restoration of BA-transforming microbial functions, rather than indiscriminate secondary BA replacement, is a rational translational direction.

129 Background: Disparities in clinical trial participation persist across racial, ethnic, and socioeconomic groups. Health literacy limitations, language barriers, and inadequate outreach infrastructure are recognized but understudied contributors to inequitable access. The National Cancer Institute Community Oncology Research Program (NCORP) aims to improve trial access in community settings. Methods: Data were drawn from the 2022 NCORP Cancer Care Delivery Research (CCDR) Landscape Assessment, a national survey of community oncology practice groups. We analyzed responses from 271 NCORP practices, focusing on health literacy screening, availability of language services, and staffing for community outreach. Associations between site characteristics and service availability were evaluated using univariable and multivariable logistic regression. Differences in patient demographics by language service availability were assessed using nonparametric tests. Statistical significance was defined as p < 0.05. Results: Only 74 (27%) sites reported routinely screening patients for health literacy. Minority/Underserved NCORP sites were significantly less likely to screen compared to others (OR 0.42, 95% CI 0.19–0.92). Language services were reported by 238 (87%) sites, with 83 (35%) using bilingual staff. Sites with bilingual staff served higher proportions of Hispanic or non-white patients (median 36% vs. 12%, p < 0.001), though language services were not associated with health literacy screening. Just 52 (19%) sites had dedicated outreach staff to recruit underrepresented populations. Outreach staffing was more common at Minority/Underserved sites (OR 3.33, 95% CI 1.61–6.92) and larger practices. Conclusions: Substantial variability exists in site-level capacity to support inclusive trial participation. Health literacy screening remains underutilized, particularly at sites serving underrepresented populations. Language services are more commonly available throughout the NCORP as compared to health literacy screening. Outreach staffing is limited, despite its potential to address access barriers. Standardizing screening practices, strengthening language infrastructure, and investing in outreach may enhance equity in oncology trial enrollment across diverse communities.

Pathology of the long head of the biceps tendon can be treated surgically with a multitude of tenodesis techniques; however, there is a lack of consensus on which technique provides the most optimal outcomes. Commonly used methods include inlay tenodesis with a bone tunnel and interference screw construct and onlay tenodesis with anchors or unicortical buttons. Although current methods typically provide satisfactory outcomes, many surgeons believe complications and failure rates remain suboptimal across techniques. In this article, we present an arthroscopic suprapectoral biceps tenodesis technique using an anchor device that was developed to address the shortcomings of current techniques, optimize outcomes, and minimize risk.

The radius of curvature (ROC) of the femoral condyle is a factor in potential cartilage incongruities following osteochondral allograft (OCA) transplantation. Accurate restoration of the chondral surface may be achievable by using "best-fit" donor-recipient matching based on linear femorotibial dimensions, such as the femoral condyle anterior-posterior length (APL), femoral condyle width (lateral-medial length, LML), femoral hemicondyle width (HCW), and tibial plateau width (TPW), particularly if they correlate well with the ROC. This study aimed to investigate the correlative relationship between femorotibial dimensions and the ROC. Computed tomography (CT) scans from 49 patients (31 men 28 ± 10 years old and 18 women 27 ± 6 years old) were analyzed. Axial images were used for APL and LML measurements, while coronal images were used for HCW and TPW. True sagittal images of the medial femoral condyle (MFC) and lateral femoral condyle (LFC) were used to calculate their individual ROCs by determining the best-fit circles along the condylar surface. Linear regression models were used to determine the relationship between the femorotibial dimensions and ROC. Measurements were repeated for a randomly selected subset of the data, and intraclass correlation coefficients (ICCs) were calculated to investigate intra- and interobserver reliability. All femorotibial dimensions showed significant correlations with the MFC and LFC ROCs (p < 0.01). The ROC correlations with femorotibial dimensions were found to be in the following descending order: APL (R 2 ≥ 0.83), LML (R 2 ≥ 0.52), TPW (R 2 ≥ 0.36), and HCW (R 2 ≥ 0.27). The intra- and interobserver reliabilities for the APL (ICC > 0.98) and ROC (ICC > 0.94) were excellent. The ROC was strongly correlated with the APL of the MFC and LFC. Donor-recipient APL matching in OCA transplantation may provide a level of matching similar to that achievable by direct ROC measurements. Determining the most predictive femorotibial dimension for ROC restoration in the OCA matching process may improve clinical outcomes, particularly for patients with large osteochondral lesions.

Desirability of outcome ranking (DOOR) is an innovative approach to clinical trial design and analysis that uses an ordinal ranking system to incorporate the overall risks and benefits of a therapeutic intervention into a single measurement. Here we derived and evaluated a disease-specific DOOR endpoint for registrational trials for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP). Through comprehensive examination of data from nearly 4000 participants enrolled in six registrational trials for HABP/VABP submitted to the Food and Drug Administration (FDA) between 2005 and 2022, we derived and applied a HABP/VABP specific endpoint. We estimated the probability that a participant assigned to the study treatment arm would have a more favorable overall DOOR or component outcome than a participant assigned to comparator. DOOR distributions between treatment arms were similar in all trials. DOOR probability estimates ranged from 48.3% to 52.9% and were not statistically different. There were no significant differences between treatment arms in the component analyses. Although infectious complications and serious adverse events occurred more frequently in ventilated participants compared to non-ventilated participants, the types of events were similar. Through a data-driven approach, we constructed and applied a potential DOOR endpoint for HABP/VABP trials. The inclusion of syndrome-specific events may help to better delineate and evaluate participant experiences and outcomes in future HABP/VABP trials and could help inform data collection and trial design.

ObjectiveTo examine the association between size and margin status of ductal carcinoma in situ (DCIS) and risk of developing ipsilateral invasive breast cancer and ipsilateral DCIS after treatment, and stage and subtype of ipsilateral invasive breast cancer.DesignMultinational, pooled cohort study.SettingFour large international cohorts.ParticipantsPatient level data on 47 695 women with a diagnosis of pure, primary DCIS between 1999 and 2017 in the Netherlands, UK, and US who underwent surgery, either breast conserving or mastectomy, often followed by radiotherapy or endocrine treatment, or both.Main outcome measuresThe main outcomes were 10 year cumulative incidence of ipsilateral invasive breast cancer and ipsilateral DCIS estimated in relation to DCIS size and margin status, and adjusted hazard ratios and 95% confidence intervals, estimated using multivariable Cox proportional hazards analyses with multiple imputed dataResultsThe 10 year cumulative incidence of ipsilateral invasive breast cancer was 3.2%. In women who underwent breast conserving surgery with or without radiotherapy, only adjusted risks for ipsilateral DCIS were significantly increased for larger DCIS (20-49 mm) compared with DCIS <20 mm (hazard ratio 1.38, 95% confidence interval 1.11 to 1.72). Risks for both ipsilateral invasive breast cancer and ipsilateral DCIS were significantly higher with involved compared with clear margins (invasive breast cancer 1.40, 1.07 to 1.83; DCIS 1.39, 1.04 to 1.87). Use of adjuvant endocrine treatment was not significantly associated with a lower risk of ipsilateral invasive breast cancer compared to treatment with breast conserving surgery only (0.86, 0.62 to 1.21). In women who received breast conserving treatment with or without radiotherapy, higher DCIS grade was not significantly associated with ipsilateral invasive breast cancer, only with a higher risk of ipsilateral DCIS (grade 1: 1.42, 1.08 to 1.87; grade 3: 2.17, 1.66 to 2.83). Higher age at diagnosis was associated with lower risk (per year) of ipsilateral DCIS (0.98, 0.97 to 0.99) but not ipsilateral invasive breast cancer (1.00, 0.99 to 1.00). Women with large DCIS (≥50 mm) more often developed stage III and IV ipsilateral invasive breast cancer compared to women with DCIS <20 mm. No such association was found between involved margins and higher stage of ipsilateral invasive breast cancer. Associations between larger DCIS and hormone receptor negative and human epidermal growth factor receptor 2 positive ipsilateral invasive breast cancer and involved margins and hormone receptor negative ipsilateral invasive breast cancer were found.ConclusionsThe association of DCIS size and margin status with ipsilateral invasive breast cancer and ipsilateral DCIS was small. When these two factors were added to other known risk factors in multivariable models, clinicopathological risk factors alone were found to be limited in discriminating between low and high risk DCIS.

Abstract The sparse hierarchical clustering (SHC) method and the R package “sparcl” are used for consumer segmentation with 247 perimenopausal and postmenopausal US women. The data includes 11 menopause rating scale (MRS) attributes measuring severity of symptoms collected in the first week of a 12‐week extended use menopause tablet perceptual efficacy study. SHC is one of the advanced statistical clustering approaches for high‐dimensional data with potential noise variables. Sparse clustering is an important topic of the actively developing field of statistical learning with sparsity. An advantage of the SHC method is that it simultaneously finds the clusters of subjects and the important clustering variables. It allows clustering the data in low‐dimensional subspaces without dimension reduction of the data before clustering. The SHC method is particularly applicable to consumer segmentation based on high‐dimensional consumer data.Practical ApplicationsSparse hierarchical clustering (SHC) provides advantages in consumer segmentation based on high‐dimensional consumer data with potential noise variables. This advanced clustering method finds the relative importance of attributes in clustering, helping to identify homogeneous clusters and enhance understanding of how consumer responses/needs vary among clusters.

PurposeTo investigate surgeon preferences for graft use, including biologic augmentation and superior capsular reconstruction (SCR) associated with surgical treatment of rotator cuff repair (RCR).MethodsA 26-question survey was completed by arthroscopic shoulder surgeons. Surgeon demographics were evaluated. Surgeons were queried about shoulder arthroscopic graft use and rationale then responses were analyzed based on demographics.ResultsIn total, 260 surgeons completed the survey. Fifty-one percent of surgeons reported a decrease in the volume of SCR use in the past 5 years. Less than 3% of surgeons used SCR in >90% of irreparable RCR cases, compared with 38% using SCR in <10% of irreparable cases (P < .05). Surgeons performing >100 RCR annually (42%; P < .05) and those employed in the hospital setting (44%; P < .05) reported an overall increase in the use of SCR. More international surgeons (67%) decreased their use of SCR compared with U.S. surgeons (44%; P < .05). In contrast, bioinductive graft use is generally on the rise, with 48% of surgeons reporting increased use since first use, although used in <10% of cases by 54% of surgeons. Sixty-eight percent of surgeons performing >100 RCRs annually used bioinductive grafts (P < .05). Fewer international surgeons (30%) performed biologic augmentation (P < .05). Suboptimal published outcomes (40%) and no perceived patient benefit (40%) were most cited for decreased SCR use. Surgeons reporting increased use cited improved personal patient outcomes (72%).ConclusionsArthroscopic surgeons report decrease in volume of SCR use in the past 5 years. Surgeon’s personal experience of patient outcome and suboptimal published results were the strongest factors impacting decision-making. In contrast, bioinductive graft use is increasing. However, most surgeons use these grafts in a relatively small percentage of cases.Clinical RelevanceEvaluation of scientific data, personal experience, and influences on surgical practice will give a comprehensive understanding of current RCR practices.

Abstract This article explores the two‐interval, two‐alternative forced‐choice (2I2AFC) paradigm in signal detection theory (SDT), which can also be called the paired A‐Not A with AB and BA pairs in the sensory and consumer fields. The article describes how to estimate the parameters and their variances from the psychometric function of the method. Tables and R codes were developed and are provided for the estimations. The performance of the method is evaluated. It shows that the paired A‐Not A with AB and BA pairs is more effective and powerful than the conventional A‐Not A and the A‐Not A with reminder (A‐Not AR) tests. An extension of the method, that is, the ratings of the paired A‐Not A with AB and BA pairs is also explored. A facial shine case study applying this method is provided.Practical applicationsAs one of the paired versions of sensory discrimination methods, the paired A‐Not A with AB and BA pairs has wide potential applications to detect and measure sensory difference, especially to detect and measure before‐after treatment effects of products. The method can be used to detect both product effects and serving order effects.