Citations

Abstract Foreign body response is a common yet serious challenge for biomedical implants. It can trigger inflammation and eventually lead to the formation of a fibrotic capsule, which compromises device function. Although significant efforts have been made to develop antifibrotic surface coatings for implantable materials, developing broadly applicable solutions remains challenging due to the diversity of materials used in biomedical implants. Here, we propose a simple and versatile strategy to develop antifibrotic coatings for biomedical implants. Photoreactive benzophenone groups are incorporated into designer polymers to enable covalent attachment to various substrates. The effect of benzophenone group density within polymer chains on surface coating efficiency was investigated, and an optimal BP incorporation ratio was identified. Polymers incorporating varying ratios of an anti-fibrotic small molecule and anti-fouling zwitterionic moieties were synthesized and successfully attached to silicone implants. In vivo evaluation of these implants in C57BL/6 mice identified an optimized polymer composition that reduced fibrotic capsule thickness by around 60%. Coating of commercial medical catheters with this optimized polymer reduced collagen deposition by over 3.5-fold following 4 weeks of implantation in the peritoneal space of C57BL/6 mice. Finally, we demonstrated that the optimized polymer coating can be readily applied to a variety of commonly used biomedical materials using this straightforward method, highlighting the versatility of the approach. This work provides a facile and broadly applicable strategy for developing antifibrotic coatings, which has the potential to expand the design of surface modifications aimed at improving the performance of biomedical implants.

Background: Prior research has revealed gender disparities in the financial relationships between industry and orthopaedic surgeons. Despite attempts to level the playing field, it remains unclear whether these efforts have reduced or eliminated gender disparities in financial relationships between industry and orthopaedic surgeons. Methods: The Centers for Medicare and Medicaid Services (CMS) Open Payments database was queried from January 1, 2024, to December 31, 2024 for orthopaedic surgeons receiving “consulting fee” or “royalty or license” payments of $1,000 or more. Surgeon characteristics were recorded from the CMS database and public sources. Total payment amounts and number of payments were calculated. Characteristics were compared by gender between those receiving any industry payment, consulting payment, and royalty payment. Multivariable linear regression analyses were used to identify factors associated with payment amount and number of payments. Results were compared with a study using similar data from 2016 to 2017. Results: A total of 3,714 surgeons received industry payments, with 3,514 (95%) being men. Of those receiving royalty payments (n = 1,374), 1.5% (n = 21) were women. Of those receiving consulting payments (n = 3,122), 6.2% (n = 194) were women. Men (β = 1.57 [95% confidence interval [CI]: 0.41-2.73, p = 0.008), years of experience (β = 0.09 [95% CI: 0.07-0.12], p < 0.001), and adult reconstruction (β = 1.77 [95% CI: 0.76-2.79], p = 0.001) were associated with a greater total number of payments. Hand surgery (β = −2.57 [95% CI: 3.97 to −1.17], p < 0.001), pediatrics (β = −2.62 [95% CI: 4.60 to −0.64], p = 0.01), and sports (β = −1.12 [95% CI: 2.08 to −0.16], p = 0.02) were associated with the fewer total number of payments. Men (β = 0.34 [95% CI: 0.10-0.57], p = 0.004), years of experience (β = 0.051 [95% CI: 0.046-0.056], p < 0.001), and adult reconstruction (β = 0.47 [95% CI: 0.27-0.68], p < 0.001) were associated with greater payment amounts, while hand (β = −0.96 [95% CI: 1.24 to −0.68], p < 0.001) and pediatrics (β = −0.79 [95% CI: 1.18 to −0.39], p < 0.001) were associated with lower payment amounts. When examining trends over time, men received 1.57 (2024) vs. 5.17 (2016-2017) additional payments and 40% (2024) vs. 197% (2016-2017) larger payments compared with women. Conclusions: Gender disparities in financial relationships (i.e., number of payments and payment amounts) between industry and orthopaedic surgeons persist, though are improved compared with prior research from about a decade ago.

Background. The adoption of technical variant grafts has expanded the donor pool for pediatric liver transplantation, but it also poses a risk of portal vein thrombosis (PVT). This study evaluated risk and prognostic factors of PVT in children undergoing liver transplantation with technical variant grafts. Methods. A total of 3137 pediatric patients from 19 centers were included: 470 received split/reduced deceased donor grafts and 2667 received living donor grafts. Multivariable logistic regression was used to identify risk factors, whereas time-dependent Cox models were used to assess the impact on survival. Results. PVT occurred in 102 patients (3.3%) and was associated with increased mortality (adjusted hazard ratio, 2.86; 95% confidence interval [CI], 1.13-7.25; P = 0.027) and graft loss (adjusted hazard ratio, 9.97; 95% CI, 4.90-20.3; P < 0.001). Risk factors included younger age, lower weight, higher Pediatric End-Stage Liver Disease score, longer cold ischemia and operation times, higher graft-to-recipient weight ratio, increased red blood cell transfusions, and biliary atresia. After adjusting for center, lower weight (odds ratio, 0.84 per kg; 95% CI, 0.71-1.00; P = 0.047) and biliary atresia (odds ratio, 2.34; 95% CI, 1.10-5.00; P = 0.027) remained predictors. Five-year patient (88.4% versus 93.1%) and graft survival (82.7% versus 96.3%) were significantly inferior in patients with PVT. Conclusions. Low-weight children with biliary atresia constituted a high-risk group, highlighting the necessity for early detection and management.

Cellular senescence is an irreversible stress response, which leads to loss of cellular function and remodeling of the cellular secretory profile. In humans, pancreatic β cells undergo cellular senescence during the progression to type 2 diabetes (T2D). However, the mechanism linking β cell senescence to islet dysfunction remains unknown, and thus the therapeutic potential of targeting senescent cells in T2D is not established. Herein, we identified a subpopulation of senescent β cells expressing p21, which emerged early in the progression of T2D in humans and mice. Spatial transcriptomics and proteomics analyses confirmed senescence and loss of cellular identity in this subpopulation in humans. Functional analysis revealed lack of glucose responsiveness, high basal insulin secretion, and transcription of senescence-associated secretory phenotype (SASP) factors. SASP factors from p21 + β cells induced secondary senescence in neighboring cells, characterized by dysfunction and loss of identity. JAK inhibitors counteracted the induction of secondary senescence and restored β cell function in islets from humans with T2D and in mice fed a high-fat diet. These findings reveal the critical role of p21 + β cells in T2D pathogenesis and the therapeutic potential of targeting this pathophysiological process.

Imaging-based, single-cell, spatial transcriptomics (iSCST) of FFPE tissue enables comprehensive analysis of archived specimens while preserving spatial context, critical to an understanding of ulcerative colitis (UC) pathology. Here, we deployed a robust framework for applying iSCST to clinical FFPE mucosal biopsies from patients with UC or immune checkpoint inhibitor–induced colitis, as well as patients serving as healthy controls. iSCST using custom Xenium gene panels enabled precise detection of diverse cell subsets and disease-specific genes. We mapped transcriptionally distinct fibroblast subsets within mucosal niches, including inflammation-associated fibroblasts (IAFs), and identified colitis-specific neighborhoods formed by IAFs, monocytes, and neutrophils. Transcriptional signatures and spatial neighborhoods uncovered through iSCST were associated with vedolizumab (VDZ) response, with nonresponders exhibiting either an innate IAF-monocyte-neutrophil signature or adaptive gut-associated lymphoid tissue signature, while responders showed enrichment of an epithelial cellular neighborhood. These signatures were validated in an internal and an external dataset, supporting the existence of 2 distinct archetypes of treatment resistance to VDZ in UC. This iSCST framework provides a powerful approach for analyzing FFPE tissues, offering insights into colitis-associated cellular networks and identifying biomarkers to enhance patient risk stratification in routine clinical workflows.

Radioactive seed localization (RSL) using 125 I is widely employed for the surgical resection of nonpalpable breast lesions due to its precision and scheduling flexibility. Although clinical experience supports its safety, quantifying radiation dose to surrounding healthy breast tissue remains important for establishing conservative operational guidelines, including acceptable implant duration prior to surgery. In this study, cumulative dose to healthy breast tissue from an implanted 125 I localization seed was evaluated using two independent computational approaches: a simplified hemispherical breast model implemented in MATLAB and a Monte Carlo simulation developed in Mathematica. Both models incorporated dosimetric parameters from AAPM Task Group 43, including the dose-rate constant, radial dose function, and two-dimensional anisotropy function, along with tissue properties consistent with International Commission on Radiological Protection recommendations. Results from both models demonstrated that cumulative dose decreases rapidly with increasing distance from the seed and increases slowly with implantation time due to the low dose rate and long half-life of 125 I. At a distance of 1 cm, cumulative dose reached approximately 3–4 cGy after 5 d and approximately 50 cGy only after extended implantation times exceeding 200 d. Agreement between the MATLAB and Monte Carlo models was within expected limits given differences in deterministic and stochastic modeling approaches. These findings indicate that radiation dose to healthy breast tissue from RSL remains well below thresholds associated with deterministic effects for clinically relevant implantation times. The results support the use of a conservative “no later than” removal date while reaffirming the radiological safety and practical advantages of 125 I seed localization in breast cancer surgery.

INTRODUCTION: Computed tomography enterography (CTE) is a noninvasive cross-sectional imaging modality routinely used for diagnosis of Crohn's disease (CD) strictures. However, CTE is limited in individually defining the severity of inflammation, fibrosis, or smooth muscle hyperplasia/hypertrophy (SMH) within such strictures. We developed and internally validated a radiomics-based machine learning model for separately characterizing the degree of histopathological inflammation, fibrosis, and SMH in CD strictures and compared it with centrally read visual radiologist scoring of CTE. METHODS: This single-center, cross-sectional study included 100 patients with CD (n = 66 for discovery; n = 34 for validation) with terminal ileal strictures confirmed on diagnostic CTE within 15 weeks of intestinal resection. Histopathological specimens were scored for inflammation, fibrosis, and SMH and spatially linked with corresponding pre-surgical CTE sequences. Annotated stricture regions on CTE were scored visually by radiologists as well as underwent three-dimensional radiomics-based machine-learning analysis; both evaluated against histopathology scoring. RESULTS: Three distinct sets of radiomic features capturing textural heterogeneity within strictures were separately linked with severe inflammation, fibrosis, and SMH across both discovery (accuracy = 0.74, 0.71, 0.71, respectively) and validation (accuracy = 0.74, 0.68, 0.68, respectively) cohorts. Radiologist visual scoring was limited, with accuracy of 0.51 for identifying severe inflammation, 0.48 for severe fibrosis, and 0.58 for severe SMH. Augmenting radiologist scoring with radiomic features yielded improved performance in identifying severe inflammation, fibrosis, or SMH compared to radiologist scoring alone. DISCUSSION: Radiomic features of CD strictures on CTE can identify severe histopathological fibrosis, inflammation, and smooth muscle hyperplasia and perform better than radiologist visual scoring in stricture characterization.

Background Effective hemostasis in spinal surgery is critical, especially near sensitive structures such as the spinal cord and dorsal root ganglia. Flowable hemostatic agents offer targeted control in irregular, hard-to-reach areas. This study evaluates the safety and efficacy of flowable collagen hemostat (FC) in an ovine lumbar laminectomy model with open durotomy by making a direct comparison with the gelatin hemostatic matrix with thrombin (GM) and a no-treatment control (Sham). Methods Fifty-four Polypay sheep (27 F, 27 M) underwent lumbar laminectomy and open durotomy and then received FC, GM, or no treatment ( n = 18/group). Hemostasis was assessed at 3 min postapplication without tamponade. Neurological examinations were performed at periodic intervals, and tissues were collected on days 7, 45, and 120 for a histological analysis. Results Hemostasis was achieved in 100% of FC-treated sites, 94.4% of GM, and 72.2% of Sham. Sham-treated animals exhibited more severe and prolonged neurological deficits compared with those treated with FC or GM. Inflammation decreased significantly across all groups, from mild/moderate on day 7 to minimal on day 45, and was barely detectable by day 120. FC was associated with favorable histological responses in both intradural and extradural spinal tissues, comparable to GM and Sham. Conclusion Flowable collagen hemostat was safe and effective when applied directly to the spinal cord and surrounding neurological tissues during laminectomy with open durotomy. Its performance was comparable to that of the gelatin hemostatic matrix with thrombin in terms of hemostatic efficacy and histological outcomes, with both agents demonstrating superior neurological recovery compared with the untreated Sham group.

This review identifies the menopausal transition as a critical yet underrecognized determinant of asthma heterogeneity in midlife women. It synthesizes evidence that fluctuating sex hormones may shape distinct asthma phenotypes and endotypes, influencing clinical manifestations, disease modifiers, and therapeutic responses. By framing menopause-associated asthma as a biologically distinct, hormone-driven condition, the article highlights key research priorities for precision medicine approaches tailored to women’s respiratory health.