2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Screening and Monitoring of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding screening for interstitial lung disease (ILD) and the monitoring for ILD progression in people with systemic autoimmune rheumatic diseases (SARDs), specifically rheumatoid arthritis, systemic sclerosis, idiopathic inflammatory myopathies, mixed connective tissue disease, and Sjögren disease. METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions related to screening and monitoring for ILD in patients with SARDs. A systematic literature review was performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A Voting Panel of interdisciplinary clinician experts and patients achieved consensus on the direction and strength of each recommendation. RESULTS: Fifteen recommendations were developed. For screening people with these SARDs at risk for ILD, we conditionally recommend pulmonary function tests (PFTs) and high-resolution computed tomography of the chest (HRCT chest); conditionally recommend against screening with 6-minute walk test distance (6MWD), chest radiography, ambulatory desaturation testing, or bronchoscopy; and strongly recommend against screening with surgical lung biopsy. We conditionally recommend monitoring ILD with PFTs, HRCT chest, and ambulatory desaturation testing and conditionally recommend against monitoring with 6MWD, chest radiography, or bronchoscopy. We provide guidance on ILD risk factors and suggestions on frequency of testing to evaluate for the development of ILD in people with SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the screening and monitoring of ILD in people with SARDs.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.

Demographic Influences on Adult HPV Vaccination: Results from a Cross-Sectional Survey in Tennessee.

HPV is the most prevalent sexually transmitted infection in the U.S., with more than 80% of all Americans contracting it by age 45. Effective vaccines for HPV exist and were recently approved for adults aged 27-45 years, though uptake remains low in all age groups, particularly in Tennessee where 1089 cancers were attributed to HPV in 2020. Between 29 June and 17 August 2023, we conducted a cross-sectional survey to gain insights about the barriers and facilitators of HPV in 2011 adults aged 18 to 45 years in Tennessee. We developed our survey based on previous instruments to understand predictors of HPV vaccination in adults. Using descriptive statistics and bivariate and logistic regression analyses, we found higher vaccination rates in females, participants aged 18-38 years, participants with a high school education or higher, Hispanic or Latine individuals, and participants identifying as moderate or liberal. These insights highlight the need for public health interventions that consider demographic differences to successfully increase vaccination rates and reduce HPV-associated cancer risk.

An examination of the sexual health behaviors and cognitions of young U.S. community college students with respect to the intersection of gender and sexual identity.

Objective: To assess the sexual health of young community college students so that health promotion priorities can be identified and tailored programming can be implemented for this understudied population. Participants: A national sample of 1,678 community college students. Methods: Survey data was analyzed to understand trends in sexual health - including differences by gender and sexual identity. Results: While 54% of the sample have had vaginal sex and 16% have had anal sex, rates of condom use for these behaviors are low (respectively 51% and 42%). Only 52% of students have communicated with a medical professional about sexual health and 42% have been tested for STIs. Young men have the lowest odds of communicating with a medical professional about sexual health. Heterosexual men have particularly low odds of getting tested for STIs. Conclusions: Community college students need additional resources - eg, education, accessible health care - to promote their sexual health.

2023 American College of Rheumatology (ACR)/American College of Chest Physicians (CHEST) Guideline for the Treatment of Interstitial Lung Disease in People with Systemic Autoimmune Rheumatic Diseases.

OBJECTIVE: We provide evidence-based recommendations regarding the treatment of interstitial lung disease (ILD) in adults with systemic autoimmune rheumatic diseases (SARDs). METHODS: We developed clinically relevant population, intervention, comparator, and outcomes questions. A systematic literature review was then performed, and the available evidence was rated using the Grading of Recommendations, Assessment, Development, and Evaluation methodology. A panel of clinicians and patients reached consensus on the direction and strength of the recommendations. RESULTS: Thirty-five recommendations were generated (including two strong recommendations) for first-line SARD-ILD treatment, treatment of SARD-ILD progression despite first-line ILD therapy, and treatment of rapidly progressive ILD. The strong recommendations were against using glucocorticoids in systemic sclerosis-ILD as a first-line ILD therapy and after ILD progression. Otherwise, glucocorticoids are conditionally recommended for first-line ILD treatment in all other SARDs. CONCLUSION: This clinical practice guideline presents the first recommendations endorsed by the American College of Rheumatology and American College of Chest Physicians for the treatment of ILD in people with SARDs.

Variants in Vitamin D-related Genes and Prostate Cancer Risk in Black Men.

BACKGROUND: The relationship between vitamin D and prostate cancer has primarily been characterized among White men. However, Black men have higher prostate cancer incidence and mortality rates, chronically low circulating vitamin D levels, and ancestry-specific genetic variants in vitamin D-related genes. Here, we examine six critical genes in the vitamin D pathway and prostate cancer risk in Black men. METHODS: We assessed a total of 69 candidate variants in six genes ( GC, CYP27A1, CYP27B1, CYP24A1, VDR , and RXRA ) including functional variants previously associated with prostate cancer and circulating 25(OHD) in White men. Associations with prostate cancer risk were examined using genome-wide association study data for approximately 10,000 prostate cancer cases and 10,000 controls among Black men and over 85,000 cases and 91,000 controls among White men. A statistical significance threshold of 0.000724 was used to account for the 69 variants tested. RESULTS: None of the variants examined were significantly associated with prostate cancer risk among Black men after multiple comparison adjustment. Four variants tested P<0.05 in Black men, including two in RXRA (rs41400444 OR=1.09, 95% CI: 1.01-1.17, P = 0.024 and rs10881574 OR = 0.93, 0.87-1.00, P = 0.046) and two in VDR (rs2853563 OR = 1.07, 1.01-1.13, P = 0.017 and rs1156882 OR = 1.06, 1.00-1.12, P = 0.045). Two variants in VDR were also positively associated with risk in White men (rs11568820 OR = 1.04, 1.02-1.06, P = 0.00024 and rs4516035 OR = 1.03, 1.01-1.04, P = 0.00055). CONCLUSION: We observed suggestive non-significant associations between genetic variants in RXRA and VDR and prostate cancer risk in Black men. Future research exploring the relationship of vitamin D with cancer risk in Black men will need larger sample sizes to identify ancestry-specific variants relevant to risk in this population.

A novel paradigm for measuring prediction abilities in a rat model using a speech-sound discrimination task.

The ability to predict and respond to upcoming stimuli is a critical skill for all animals, including humans. Prediction operates largely below conscious awareness to allow an individual to recall previously encountered stimuli and prepare an appropriate response, especially in language. The ability to predict upcoming words within typical speech patterns aids fluent comprehension, as conversational speech occurs quickly. Individuals with certain neurodevelopmental disorders such as autism and dyslexia have deficits in their ability to generate and use predictions. Rodent models are often used to investigate specific aspects of these disorders, but there is no existing behavioral paradigm that can assess prediction capabilities with complex stimuli like speech sounds. Thus, the present study modified an existing rapid speech sound discrimination paradigm to assess whether rats can form predictions of upcoming speech sound stimuli and utilize them to improve task performance. We replicated prior work showing that rats can discriminate between speech sounds presented at rapid rates. We also saw that rats responded exclusively to the target at slow speeds but began responding to the predictive cue in anticipation of the target as the speed increased, suggesting that they learned the predictive value of the cue and adjusted their behavior accordingly. This prediction task will be useful in assessing prediction deficits in rat models of various neurodevelopmental disorders through the manipulation of both genetic and environmental factors.

A Narrative Review of Pain in Pediatric Oncology: The Opioid Option.

Opioid therapy is the mainstay for managing pain in pediatric oncology. This narrative review describes the current literature regarding opioids for pediatric cancer pain. The review explores the multifaceted landscape of opioid utilization in this population, including the role of opioids in certain clinical circumstances, modalities of opioid delivery, unique opioids, outpatient and at-home pain management strategies, and other key concepts such as breakthrough pain. This review highlights the importance of individualized dosing and multimodal approaches to enhance efficacy and minimize adverse effects. Drawing from a wide range of evidence, this review offers insights to optimize pediatric oncology pain management.

Cognitive Profiles are Better Predictors of Literacy Attainment Than Diagnostic Outcomes in Children with High ADHD Symptoms.

We examined whether cognitive profiles or diagnostic outcomes are better predictors of literacy performance for children being considered for an ADHD diagnosis. Fifty-five drug naïve children (Mage = 103.13 months, SD = 18.65; 29.09% girls) were recruited from an ADHD clinical referral waiting list. Children underwent assessment of IQ, Executive Functions (EF) and literacy attainment. Hierarchical cluster analysis was used to generate subgroups of children using EF scores. Data were then grouped based on presence of a clinical ADHD diagnosis and the results compared. Grouping participants by profiles of cognitive test scores led to groups which also differed on literacy scores. However, categorising by whether children had received an ADHD diagnosis or not did not differentiate either cognitive tests scores or literacy scores. Cognitive performance, rather than children's diagnostic outcomes, is more informative for identifying groups who differ in their literacy attainment which has important implications for remedial support.

Care Partners' Engagement in Preventing Falls for Community-Dwelling Older People With Dementia.

BACKGROUND AND OBJECTIVES: Little is known about how to prevent falls in community-dwelling older people with dementia. Although their care partners adopt various behaviors to prevent their falls, it is unclear if these behaviors reduce falls for those with different levels of fall risk. RESEARCH DESIGN AND METHODS: Linking the 2015 and 2016 National Health and Aging Trends Study and the 2015 National Study of Caregiving (NSOC), we identified 390 community-dwelling older people with dementia with 607 care partners. We selected 26 NSOC items representing fall risk management (FRM) behaviors. We examined the prevalence and dimensionality of these behaviors and investigated associations between care partners' behaviors in 2015 (T1) and older people's falls in 2016 (T2) stratified by their fall incidence at T1, adjusting for covariates. RESULTS: Five domains of FRM were identified: mobility and safety assistance, medical service coordination, health management, social service coordination, and accommodation. For those who did not fall at T1, mobility and safety assistance and social service coordination were each associated with an increased risk of falling at T2 (adjusted incidence rate ratio [aIRR] = 1.39, 95% confidence interval [CI] = 1.06-1.83, p = .019, aIRR = 1.25, 95% CI = 1.01-1.55, p = .043). For those who had fallen at T1, social service coordination was associated with a decreased risk of falling at T2 (aIRR = 0.83, 95% CI = 0.73-0.94, p = .004). DISCUSSION AND IMPLICATIONS: The different impacts of dementia care partners' FRM behaviors emphasize the need to address specific behaviors when involving care partners in preventing falls for older people with dementia at varying levels of fall risk.

Evaluating the Effectiveness of Expert Modeling Videos on Nursing Student Competency Behaviors.

BACKGROUND: Expert modeling videos (EMVs) have shown promise in improving students' performance in simulation. However, research evaluating the impact of EMVs is limited to major performance areas, lacking exploration into specific student competency behaviors. PURPOSE: This study evaluated the effect of an EMV intervention on undergraduate nursing students' behavioral competencies as measured by the Creighton Competency Evaluation Instrument (CCEI). METHODS: Using a quasi-experimental pragmatic evaluation design, students in a medical surgical nursing course (n = 160) viewed either an expert model demonstration video (experimental) or expert model discussion video (control). Students' behavioral competencies were measured and compared between groups using the CCEI. RESULTS: Students who viewed an expert model demonstration video performed at a higher level of competency in 11 of the 18 CCEI behaviors. CONCLUSION: Using EMVs in nursing simulation may improve students' ability to achieve clinical competency in nursing specific behaviors.

Efficacy of Intravesical Nadofaragene Firadenovec for Patients With Bacillus Calmette-Guérin-Unresponsive Nonmuscle-Invasive Bladder Cancer: 5-Year Follow-Up From a Phase 3 Trial.

PURPOSE: Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector-based gene therapy for bacillus Calmette-Guérin (BCG)-unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up. MATERIALS AND METHODS: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50). Patients received 75 mL (3 × 1011 vp/mL) nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology assessments, with continued treatment offered to those remaining high grade recurrence-free (HGRF). RESULTS: One hundred fifty-seven patients were enrolled from 33 US sites (n = 151 included in efficacy analyses). Median follow-up was 50.8 months (interquartile range 39.1-60.0), with 27% receiving ≥ 5 instillations and 7.6% receiving treatment for ≥ 57 months. Of patients with CIS 5.8% (95% CI 2.2-12.2) were HGRF at month 57, and 15% (95% CI 6.1-27.8) of patients with high-grade Ta/T1 were HGRF at month 57. Kaplan-Meier-estimated HGRF survival at 57 months was 13% (95% CI 6.9-21.5) and 33% (95% CI 19.5-46.6) in the CIS and Ta/T1 cohorts, respectively. Cystectomy-free survival at month 60 was 49% (95% CI 40.0-57.1): 43% (95% CI 32.2-53.7) in the CIS cohort and 59% (95% CI 43.1-71.4) in the Ta/T1 cohort. Overall survival at 60 months was 80% (71.0, 86.0): 76% (64.6-84.5) and 86% (70.9-93.5) in the CIS and Ta/T1 cohorts, respectively. Only 5 patients (4 with CIS and 1 with Ta/T1) experienced clinical progression to muscle-invasive disease. CONCLUSIONS: At 60 months, nadofaragene firadenovec-vncg allowed bladder preservation in nearly half of the patients and proved to be a safe option for BCG-unresponsive nonmuscle-invasive bladder cancer.

Surgical interventions and short-term outcomes for preterm infants with post-haemorrhagic hydrocephalus: a multicentre cohort study.

OBJECTIVE: To (1) describe differences in types and timing of interventions, (2) report short-term outcomes and (3) describe differences among centres from a large national cohort of preterm infants with post-haemorrhagic hydrocephalus (PHH). DESIGN: Cohort study of the Children's Hospitals Neonatal Database from 2010 to 2022. SETTING: 41 referral neonatal intensive care units (NICUs) in North America. PATIENTS: Infants born before 32 weeks' gestation with PHH defined as acquired hydrocephalus with intraventricular haemorrhage. INTERVENTIONS: (1) No intervention, (2) temporising device (TD) only, (3) initial permanent shunt (PS) and (4) TD followed by PS (TD-PS). MAIN OUTCOME MEASURES: Mortality and meningitis. RESULTS: Of 3883 infants with PHH from 41 centres, 36% had no surgical intervention, 16% had a TD only, 19% had a PS only and 30% had a TD-PS. Of the 46% of infants with TDs, 76% were reservoirs; 66% of infants with TDs required PS placement. The percent of infants with PHH receiving ventricular access device placement differed by centre, ranging from 4% to 79% (p<0.001). Median chronological and postmenstrual age at time of TD placement were similar between infants with only TD and those with TD-PS. Infants with TD-PS were older and larger than those with only PS at time of PS placement. Death before NICU discharge occurred in 12% of infants, usually due to redirection of care. Meningitis occurred in 11% of the cohort. CONCLUSIONS: There was significant intercentre variation in rate of intervention, which may reflect variability in care or referral patterns. Rate of PS placement in infants with TDs was 66%.

The Impact of the COVID-19 Pandemic on Patient Disparities in Long-Term Opioid Therapy.

BACKGROUND: The COVID-19 pandemic disrupted how primary care patients with chronic pain received care. Our study sought to understand how long-term opioid therapy (LtOT) for chronic pain changed over the course of the pandemic overall and for different demographic subgroups. METHODS: We used data from electronic health records of 64 primary care clinics across Washington state and Idaho to identify patients who had a chronic pain diagnosis and were receiving long-term opioid therapy. We defined 10-month periods in 2019 to 2021 as prepandemic, early pandemic and late pandemic and used generalized estimating equations analysis to compare across these time periods and demographic characteristics. RESULTS: We found a proportional decrease in LtOT for chronic pain in the early months of the pandemic (OR = 0.94, P = .007) followed by an increase late pandemic (OR = 1.08, P = .002). Comparing late pandemic to prepandemic, identifying as Asian or Black, having fewer comorbidities, or living in an urban area were associated with higher likelihood of being prescribed LtOT. DISCUSSION: The use of LtOT for chronic pain in primary care has increased from before to after the COVID-19 pandemic with racial/ethnic and geographic disparities. Future research is needed to understand these disparities in LtOT and their effect on patient outcomes.

Boswellia serrata Enhances Passive Range-of-Motion Exercises in Radiation-Induced Trismus: A Case Report.

Trismus is a common, extremely detrimental side effect following definitive radiotherapy for head and neck malignancies. Existing therapeutic modalities (active and passive range-of-motion exercises and systemic therapies) offer only modest, slow improvements in jaw opening; thus, there is a need for additional treatment options. Boswellia serrata (BS) ("Indian frankincense") is a tree native to West Asia and North Africa that produces resin-containing "boswellic" acids. These have been shown to have in vitro and in vivo anti-inflammatory effects and have previously been found to be an effective treatment for asthma, colitis, arthritis, and post-radiation edema. Herein we report the case of a 54-year-old male with severe post-radiation trismus who experienced a dramatic resolution with BS/Therabite® combination therapy. His trismus improved from 6 mm to 45 mm over 10 weeks (0.46 mm/day), far exceeding previous rates of improvement documented in the literature. There were no ill effects. Given the dearth of effective treatments for post-radiation trismus, BS is a promising agent deserving of further study.

Adaptation of the Mycobacterium tuberculosis transcriptome to biofilm growth.

Mycobacterium tuberculosis (M. tb), the causative agent of tuberculosis (TB), is a leading global cause of death from infectious disease. Biofilms are increasingly recognized as a relevant growth form during M. tb infection and may impede treatment by enabling bacterial drug and immune tolerance. M. tb has a complicated regulatory network that has been well-characterized for many relevant disease states, including dormancy and hypoxia. However, despite its importance, our knowledge of the genes and pathways involved in biofilm formation is limited. Here we characterize the biofilm transcriptomes of fully virulent clinical isolates and find that the regulatory systems underlying biofilm growth vary widely between strains and are also distinct from regulatory programs associated with other environmental cues. We used experimental evolution to investigate changes to the transcriptome during adaptation to biofilm growth and found that the application of a uniform selection pressure resulted in loss of strain-to-strain variation in gene expression, resulting in a more uniform biofilm transcriptome. The adaptive trajectories of transcriptomes were shaped by the genetic background of the M. tb population leading to convergence on a sub-lineage specific transcriptome. We identified widespread upregulation of non-coding RNA (ncRNA) as a common feature of the biofilm transcriptome and hypothesize that ncRNA function in genome-wide modulation of gene expression, thereby facilitating rapid regulatory responses to new environments. These results reveal a new facet of the M. tb regulatory system and provide valuable insight into how M. tb adapts to new environments.

Periventricular nodular heterotopia in patients with a prenatal diagnosis of myelomeningocele/myeloschisis: associations with seizures and neurodevelopmental outcomes during early childhood.

PURPOSE: Historically, the presence of gray matter heterotopia was a concern for adverse postnatal neurocognitive status in patients undergoing fetal closure of open spinal dysraphism. The purpose of this study was to evaluate neurodevelopmental outcomes and the onset of seizures during early childhood in patients with a prenatal diagnosis of myelomeningocele/myeloschisis (MMC) and periventricular nodular heterotopia (PVNH). METHODS: All patients evaluated at the Center for Fetal Diagnosis and Treatment with a diagnosis of MMC between June 2016 to March 2023 were identified. PVNH was determined from prenatal and/or postnatal MRI. The Bayley Scales of Infant and Toddler Development (edition III or IV) were used for neurodevelopmental assessments. Patients were screened for seizures/epilepsy. RESULTS: Of 497 patients evaluated with a prenatal diagnosis of MMC, 99 were found to have PVNH on prenatal MRI, of which 35 had confirmed PVNH on postnatal imaging. From the 497 patients, 398 initially did not exhibit heterotopia on prenatal MRI, but 47 of these then had confirmed postnatal PVNH. The presence of PVNH was not a significant risk factor for postnatal seizures in early childhood. The average neurodevelopmental scores were not significantly different among heterotopia groups for cognitive, language, and motor domains. CONCLUSION: The presence of PVNH in patients with a prenatal diagnosis of MMC does not indicate an increased risk for neurodevelopmental delay at 1 year of age. We did not demonstrate an association with seizures/epilepsy. These findings can aid clinicians in prenatal consultation regarding fetal repair of open spinal dysraphism. Long-term follow-up is required to discern the true association between PVNH seen on prenatal imaging and postnatal seizures/epilepsy and neurodevelopmental outcomes.

EphB2 Receptor Promotes Dermal Fibrosis in Systemic Sclerosis.

OBJECTIVE: Erythropoietin-producing hepatocellular (Eph)/Ephrin cell-cell signaling is emerging as a key player in tissue fibrogenesis. The aim of this study was to test the hypothesis that the receptor tyrosine kinase EphB2 mediates dermal fibrosis in systemic sclerosis (SSc). METHODS: We assessed normal and SSc human skin biopsies for EphB2 expression. The in vivo role of EphB2 in skin fibrosis was investigated by subjecting EphB2-knockout mice to both bleomycin-induced and tight skin (Tsk1/+) genetic mouse models of skin fibrosis. EphB2 kinase-dead and overactive point mutant mice were used to evaluate the role of EphB2 forward signaling in bleomycin-induced dermal fibrosis. In vitro studies were performed on dermal fibroblasts from patients with SSc and healthy controls, which was followed by in vivo analysis of fibroblast-specific Ephb2-deficient mice. RESULTS: Expression of EphB2 is up-regulated in SSc skin tissue and explanted SSc dermal fibroblasts compared with healthy controls. EphB2 expression is elevated in two animal models of dermal fibrosis. In mice, EphB2 drives dermal fibrosis in both the bleomycin and the Tsk1/+ models of skin fibrosis. EphB2 forward signaling is a critical mediator of dermal fibrosis. Transforming growth factor-ß (TGF-ß) cytokines up-regulate EphB2 in dermal fibroblasts via noncanonical TGF-ß/mother against decapentaplegic signaling, and silencing EPHB2 in human dermal fibroblasts is sufficient to dampen TGF-ß-induced fibroblast-to-myofibroblast differentiation. Moreover, mice with fibroblast-specific deletion of EphB2 showed impaired fibroblast-to-myofibroblast differentiation and reduced skin fibrosis upon bleomycin challenge. CONCLUSION: Our data implicate TGF-ß regulation of EphB2 overexpression and kinase-mediated forward signaling in the development of dermal fibrosis in SSc. EphB2 thus represents a potential new therapeutic target for SSc.

Femoral Component Debonding Frequently Missed on Advanced Imaging Prior to Revision of a Recalled Total Knee Arthroplasty.

BACKGROUND: Identification of femoral component debonding in the work-up of painful total knee arthroplasty (TKA) often poses a diagnostic challenge. The purpose of this study was to compare the sensitivity and specificity of radiographs, computed tomography (CT), and magnetic resonance imaging (MRI) for identifying femoral component loosening with debonding at the time of revision of a primary TKA with a recalled polyethylene insert. METHODS: Using an institutional database, we identified all cases of revision TKA performed for this specific implant recall following a primary TKA between 2014 and 2022. Patients who had a preoperative radiograph, CT, and MRI were included (n = 77). Sensitivity, specificity, and positive and negative likelihood ratio (LR) for predicting loosening were compared among the imaging modalities, using the intraoperative evidence of implant loosening as the gold standard. RESULTS: At the time of revision surgery, the femoral component was noted to have aseptic loosening with debonding in 46 of the 77 (60%) of the TKAs. There were no significant differences in demographics in the cohort with femoral debonding compared to those with well-fixed implants. The CT demonstrated a sensitivity of 28% and a specificity of 97%, while the MRI demonstrated a sensitivity of 37% and a specificity of 94% for detecting femoral loosening due to debonding. Both CT and MRI demonstrated poor negative LRs for femoral loosening (LR 0.7). CONCLUSIONS: In this series of revision TKAs for a specific recalled component, neither CT nor MRI accurately diagnosed femoral component debonding. For patients who have this implant, it is imperative to interrogate the implant-cement interface intraoperatively and prepare for full revision surgery as well as marked bone loss secondary to osteolysis.