The common p.Ile291Val variant of ERLIN1 enhances TM6SF2 function and is associated with protection against MASLD.

BACKGROUND: The ERLIN1 p.Ile291Val single-nucleotide polymorphism (rs2862954) is associated with protection from steatotic liver disease (SLD), but effects of this variant on metabolic phenotypes remain uncertain. METHODS: Metabolic phenotypes and outcomes associated with ERLIN1 p.Ile291Val were analyzed by using a genome-first approach in the UK Biobank (UKB), Penn Medicine BioBank (PMBB), and All of Us cohort. FINDINGS: ERLIN1 p.Ile291Val carriers exhibited significantly lower serum levels of alanine aminotransferase and aspartate aminotransferase as well as higher levels of triglycerides, low-density lipoprotein cholesterol, Apolipoprotein B, high-density lipoprotein cholesterol, and Apolipoprotein A1 in UKB, and these values were affected by ERLIN1 p.Ile291Val in an allele-dose-dependent manner. Homozygous ERLIN1 p.Ile291Val carriers had a significantly reduced risk of developing metabolic dysfunction-associated SLD (MASLD, adjusted odds ratio [aOR] = 0.92, 95% confidence interval [CI], 0.88-0.96). The protective effect of this variant was enhanced in patients with alcoholic liver disease. Our results were replicated in PMBB and the All of Us cohort. Strikingly, the protective effects of ERLIN1 p.Ile291Val were not apparent in individuals carrying the TM6SF2 p.Glu167Lys variant associated with increased risk of SLD. We analyzed the effects of predicted loss-of-function ERLIN1 variants and found that they had opposite effects, namely reduced plasma lipids, suggesting that ERLIN1 p.Ile291Val may be a gain-of-function variant. CONCLUSION: Our study contributes to a better understanding of ERLIN1 by investigating a coding variant that has emerged as a potential gain-of-function mutation with protective effects against MASLD development.

Postmortem Digital Image Correlation and Finite Element Modeling Demonstrate Posterior Scleral Deformations during Optic Nerve Adduction Tethering.

Postmortem human eyes were subjected to optic nerve (ON) traction in adduction and elevated intraocular pressure (IOP) to investigate scleral surface deformations. We incrementally adducted 11 eyes (age 74.1 ± 9.3 years, standard deviation) from 26° to 32° under normal IOP, during imaging of the posterior globe, for analysis by three-dimensional digital image correlation (3D-DIC). In the same eyes, we performed uniaxial tensile testing in multiple regions of the sclera, ON, and ON sheath. Based on individual measurements, we analyzed eye-specific finite element models (FEMs) simulating adduction and IOP loading. Analysis of 3D-DIC showed that the nasal sclera up to 1 mm from the sheath border was significantly compressed during adduction. IOP elevation from 15 to 30 mmHg induced strains less than did adduction. Tensile testing demonstrated ON sheath stiffening above 3.4% strain, which was incorporated in FEMs of adduction tethering that was quantitatively consistent with changes in scleral deformation from 3D-DIC. Simulated IOP elevation to 30 mmHg did not induce scleral surface strains outside the ON sheath. ON tethering in incremental adduction from 26° to 32° compressed the nasal and stretched the temporal sclera adjacent to the ON sheath, more so than IOP elevation. The effect of ON tethering is influenced by strain stiffening of the ON sheath.

Association of Timing of Hindfoot Arthrodesis and Early Reoperation Rates for Total Ankle Arthroplasty.

BACKGROUND: Prior literature has demonstrated that ipsilateral hindfoot arthrodesis may increase the risk for reoperation after total ankle arthroplasty (TAA) and that simultaneous hindfoot arthrodesis with TAA could result in short-term clinical and radiologic improvements. The purpose of this study is to compare the reoperation rates after TAA with prior hindfoot arthrodesis vs simultaneous arthrodesis and TAA. METHODS: Patients who underwent primary TAA were identified in the PearlDiver database. Patients were sorted into 2 study cohorts: hindfoot arthrodesis prior to TAA and simultaneous arthrodesis and TAA. Propensity matched control cohorts were identified for each study group. Multivariate analysis was conducted to account for any confounding variables and covariates when identifying differences in complications between cohorts. RESULTS: 297 patients underwent TAA with prior hindfoot arthrodesis and 174 underwent TAA and hindfoot arthrodesis concurrently. The incidence of reoperation (13.8% vs 5.2%, P < .001) and infection (12.6% vs 5.9%, P = .011) for the simultaneous cohort was higher when compared to the matched control cohort. In contrast, there was no statistically significant difference when comparing the prior arthrodesis cohort to the matched control cohort in reoperation rates (5.1% vs 4.7%, P = .787) or infection rates (4.4% vs 4.8%, P = .734). Those undergoing simultaneous procedures had increased incidences of reoperation, wound complications, infection, and emergency department visits (P < .0167) when compared to the TAA with prior arthrodesis cohort. CONCLUSION: Patients undergoing TAA and hindfoot arthrodesis concurrently were found to have higher rates of reoperation and infection when compared to the matched control cohort . In contrast, there was no difference in these rates in patients undergoing TAA with prior hindfoot arthrodesis compared with their matched control cohort. Patients undergoing simultaneous procedures had increased rates of reoperations, wound complications, infection, and emergency department visits compared to the TAA with prior arthrodesis cohort. LEVEL OF EVIDENCE: Level III, retrospective comparative database study.

Repeat Next-Generation Sequencing Testing on Progression in Men With Metastatic Prostate Cancer Can Identify New Actionable Alterations.

PURPOSE: There are limited data available on the real-world patterns of molecular testing in men with advanced prostate cancer. We thus sought to evaluate next-generation sequencing (NGS) testing in the United States, focused on single versus serial NGS testing, the different disease states of testing (hormone-sensitive v castration-resistant, metastatic vs nonmetastatic), tissue versus plasma circulating tumor DNA (ctDNA) assays, and how often actionable data were found on each NGS test. METHODS: The Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort clinical-genomic database was used for this retrospective analysis, including 1,597 patients across 15 institutions. Actionable NGS data were defined as including somatic alterations in homologous recombination repair genes, mismatch repair deficiency, microsatellite instability (MSI-high), or a high tumor mutational burden ≥10 mut/MB. RESULTS: Serial NGS testing (two or more NGS tests with specimens collected more than 60 days apart) was performed in 9% (n = 144) of patients with a median of 182 days in between test results. For the second NGS test and beyond, 82.1% (225 of 274) of tests were from ctDNA assays and 76.1% (217 of 285) were collected in the metastatic castration-resistant setting. New actionable data were found on 11.1% (16 of 144) of second NGS tests, with 3.5% (5 of 144) of tests detecting a new BRCA2 alteration or MSI-high. A targeted therapy (poly (ADP-ribose) polymerase inhibitor or immunotherapy) was given after an actionable result on the second NGS test in 31.3% (5 of 16) of patients. CONCLUSION: Repeat somatic NGS testing in men with prostate cancer is infrequently performed in practice and can identify new actionable alterations not present with initial testing, suggesting the utility of repeat molecular profiling with tissue or blood of men with metastatic castration-resistant prostate cancer to guide therapy choices.

The effect of hypotonic pharmacologic lipodissolution on abdominal free flap perfusion: a case report.

Background: Hypotonic pharmacologic lipodissolution (HPL) has gained popularity as a treatment for abdominal fat reduction, especially among Asian individuals. However, research on the effect of HPL on abdominal vascularity and abdominal autologous tissue flap are limited. Case Description: This case report describes a patient who underwent HPL treatment in November 2022 and subsequently underwent nipple-sparing mastectomy with free transverse rectus abdominis musculocutaneous (TRAM) flap reconstruction on April 4, 2023. The preoperative evaluation included computed tomography (CT) angiography to assess the viability of abdominal perforators and vasculature for TRAM flap reconstruction. Intraoperatively, indocyanine green (ICG) fluoroscopy was performed after TRAM flap elevation to evaluate flap perfusion. The findings revealed compromised skin-side perfusion but satisfactory deep layer perfusion, with subdermal plexus perfusion observed during de-epithelialization. Conclusions: These findings suggest that in nipple sparing mastectomy cases with minimal skin flap preservation requirements, a history of HPL may have less negative impact on TRAM flap reconstruction. However, in skin sparing mastectomy cases with extensive skin flap preservation needs, careful assessment, including preoperative CT angiography and intraoperative ICG imaging, is essential to minimize the risk of partial flap necrosis.

Basal cell adenoma and basal cell adenocarcinoma of the parotid gland: clinical findings and surgical outcomes in a single-institution study.

BACKGROUND: Basal cell adenoma (BCA) is a rare benign tumor within the salivary glands. Basal cell adenocarcinoma (BCAC), the malignant counterpart of BCA, is also an exceedingly rare tumor with very limited clinical studies conducted. This study aims to investigate the clinical characteristics, demographics, and surgical outcomes of patients diagnosed with BCA and BCAC within the parotid gland. METHODS: A retrospective analysis from May 2003 to August 2023 was performed for all patients undergoing parotidectomy for masses. Retrospective data on gender, age, tumor characteristics, and outcomes were collected. Surgical approaches, including negative margin attainment, capsule removal, and histological diagnosis, were also detailed. RESULTS: The study included 1268 patients who underwent parotidectomy, resulting in 81 cases of BCA and 7 cases of BCAC. BCA patients, with a mean age of 55.1 years, showed diverse age distribution and predominantly presented in the 50s. In BCAC cases, seven female patients exhibited a predominant location in the deep lobes. FNA revealed BCAC in three out of seven cases, and subsequent parotidectomy was performed, resulting in no observed recurrences or metastases. CONCLUSION: This study reports the largest number of BCA cases from a single institution and provides comprehensive insights into the demographics, tumor characteristics, and clinical outcomes of both BCA and BCAC. Although further research should be conducted, based on clinical follow-up results, appropriately including the capsule in the tumor excision indicates favorable outcomes, especially when the tumor size is not large.

Squamous Cell Carcinoma Arising From Epidermal Cyst: A Case Series of 9 Patients With a Literature Review.

ABSTRACT: Epidermal cysts are among the most common benign subcutaneous tumors. However, malignant transformation of benign epidermal cysts into squamous carcinomas has been reported. Owing to its low incidence rate, the clinical and pathological features of this condition are not well understood. This study aimed to analyze the clinical and pathological characteristics of the malignant transformation of epidermal cysts, which could suggest an appropriate treatment strategy. We conducted a retrospective study of 9 patients diagnosed with squamous cell carcinoma arising from epidermal cysts. All patients underwent surgical excision, and clinical information regarding patient demographics, tumor characteristics, treatment, and outcomes was analyzed. The average age at diagnosis was 57.3 years, with an average latency period of 15.4 years. Five patients had undergone prior cyst excision or drainage, with an average of 2.3 episodes of recurrence. Surgical excision was the primary treatment in all cases, and 2 patients with margin involvement at the final pathology underwent re-excision with additional resection margins. No recurrence was observed during the follow-up period. Four patients had immune dysregulation due to an underlying chronic kidney disease or cancer. Our study emphasizes the need for increased awareness of squamous cell carcinoma arising from epidermal cysts in patients with a history of cyst existence or recurrence, especially those with immune deficiencies. We expect these findings to contribute to early suspicion of malignant transformation and guide adequate clinical decision-making.

Incidence of Vitamin D Deficiency in Foot and Ankle Arthrodesis Nonunions.

Background Vitamin D has been found to be crucial in musculoskeletal health. The role of vitamin D levels in orthopedic patients has become a growing area of interest given its negative impact on fracture healing which can contribute to the development of nonunion following surgery. We sought to investigate the incidence of hypovitaminosis D in a cohort of patients who experienced a nonunion following a foot and ankle arthrodesis procedure. Methodology Patients who underwent a major elective foot and ankle arthrodesis procedure and developed a nonunion were given the opportunity to obtain serum vitamin D levels. All vitamin D levels were reported from percutaneous venous blood samples and compared to our institution's range of accepted normal values (25-80 ng/mL). Results A total of 13 patients who developed a nonunion agreed to have a vitamin D level obtained, and 11 of 13 patients had a low vitamin D level (average = 14.6 ng/mL, range = 9-24 ng/mL). Five patients underwent revision arthrodesis after normalization of vitamin D levels, and four out of five patients went on to successful union. Conclusions Hypovitaminosis D may be a modifiable risk factor for nonunion following a major foot and ankle arthrodesis procedure. Orthopedic surgeons should consider vitamin D screening and supplementation in patients undergoing elective arthrodesis procedures.

The Association of Anticoagulation Intensity with Outcomes in Hospitalized COVID-19 Patients.

Venous thromboembolism (VTE) risk is increased in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A key question was whether increased intensity of anticoagulation would help prevent VTE and improve patient outcomes, including transfer to the intensive care unit (ICU) and mortality. At the start of the coronavirus disease-19 (COVID-19) pandemic, our institution, Boston Medical Center, instituted a VTE risk stratification protocol based on patients' initial D-dimer levels, medical history, and presence of thrombosis to determine whether they should receive standard-dose prophylaxis, high-dose prophylaxis, or therapeutic anticoagulation. We performed a retrospective observational cohort study examining the association of degree of anticoagulation with outcomes in 915 hospitalized COVID-19 patients hospitalized initially on the general inpatient wards between March 1,, 2020, and June 1, 2020. Patients directly hospitalized in the ICU were excluded. Most, 813 patients (89%), in our cohort were on standard-dose prophylaxis; 32 patients (3.5%) received high-dose prophylaxis; 70 patients (7.7%), were treated with therapeutic anticoagulation. VTE occurred in 45 patients (4.9%), and the overall in-hospital mortality rate was 5.4% (49 deaths). On multivariable analysis of clinical outcomes in relation to type of anticoagulation, in the high-dose prophylaxis group, there was a trend towards increased in-hospital mortality (odds ratio 2.4 (0.8-7.5, 95% CI)) and increased ICU transfer (odds ratio 2.2 (0.9-5.7, 95% CI)). Our results suggest that patients receiving high-dose prophylaxis had more severe disease that was not mitigated by intermediate-dose anticoagulation.

Cyclic High Negative-Pressure External Volume Expansion Reduces Daily Device Application Time With Similar Effects on Recipient Site Preparation in a Murine Model.

Introduction: Recipient site preparation using external volume expansion (EVE) increases graft survival in large-volume fat grafting. To improve patient compliance with using the device, we tested a new cyclic high negative-pressure (CHNP) mode that involves 1 h/day at -55 mm Hg, cycled between 1-second negative-pressure activation, followed by a 2-second deactivation period in an animal model. Material and Method: A miniaturized EVE device was applied to 30 8-week-old male Sprague-Dawley rats. The rats were assigned to 3 groups (no pressure for the control group, conventional -25 mm Hg for 8 h/day for conventional EVE, and CHNP mode for the CHNP group). After 28 days, micro-computed tomography was performed and skin biopsy specimens were obtained. Results: The CHNP group showed a 6.6-fold increase and the conventional EVE group showed a 4.4-fold increase in volume compared to the control group. Hematoxylin and eosin staining showed a similar increase in subcutaneous tissue thickness in both EVE groups, compared to the control group. Masson's trichome and proliferating cell nuclear antigen staining showed significantly higher collagen deposition and subdermal adipocytes in EVE groups. Immunohistochemistry against platelet endothelial cell adhesion molecule 1 showed 2.5- and 2.7-times higher vessel density in the conventional and CHNP EVE groups, respectively. There was no statistically significant difference in subcutaneous tissue thickness, collagen deposition, subdermal adipocyte proliferation, and vessel density between the 2 EVE groups. Conclusion: CHNP produced comparable results in recipient site preparation (subcutaneous tissue thickening and angiogenesis) compared to the conventional protocol, while markedly reducing the daily wear-time from 8 hours to 1 hour. Although further clinical data must be acquired, our new pressure setting seems promising and provides a more patient-friendly pre-expansion environment.

Introduction: La préparation du site receveur utilisant l'expansion de volume externe (EVE) augmente la survie d'une greffe dans une greffe de tissu adipeux de grand volume. Pour améliorer l'observance de l'utilisation du dispositif par le patient, nous avons testé un nouveau mode cyclique à forte pression négative (CHNP) qui implique 1 heure par jour à −55 mm Hg, dans un cycle entre une activation de pression négative 1-s suivie d'une période de désactivation de 2-s dans un modèle animal. Matériel et Méthode: Un dispositif EVE miniaturisé a été appliqué à 30 rats mâles Sprague-Dawley âgés de 8 semaines. Les rats ont été répartis en trois groupes (pas de pression dans le groupe témoin, pression conventionnelle de −25 mm Hg pendant 8 h/jour pour l'EVE conventionnelle et forte pression cyclique négative pour le groupe CHNP). Après 28 jours, une micro-tomodensitométrie (TDM) a été réalisée et des échantillons de biopsie de peau ont été prélevés. Résultats: Le groupe CHNP avait une augmentation de 6,6 fois, et le groupe d'EVE conventionnelle présentait une augmentation de 4,4 fois le volume comparativement au groupe contrôle. La coloration à l'hématoxyline-éosine a mis en évidence une augmentation similaire de l'épaisseur du tissu sous-cutané dans les 2 groupes EVE, par rapport au groupe contrôle. Le trichrome de Masson et la coloration pour l'antigène nucléaire de prolifération cellulaire (PCNA) ont montré un dépôt de collagène significativement plus important et des adipocytes sous-dermiques plus nombreux dans les groupes EVE. L'immunohistochimie contre les molécules d'adhésion-1 des cellules endothéliales d'origine plaquettaire a montré une densité vasculaire plus élevée de 2,5 fois et 2,7 fois dans, respectivement, les groupes EVE conventionnelle et EVE CHNP. Il n'y a pas eu de différence statistiquement significative concernant l'épaisseur du tissu sous-cutané, le dépôt de collagène, la prolifération des adipocytes sous-dermiques et la densité des vaisseaux sanguins entre les deux groupes EVE. Conclusion: La forte pression négative cyclique a obtenu des résultats comparables pour la préparation d'un site receveur (épaississement du tissu sous-cutané et angiogenèse) comparativement au protocole conventionnel, tout en ayant une durée de port quotidien nettement réduite de 8 heures à 1 heure. Des données cliniques supplémentaires doivent être obtenues, mais notre nouveau cadre de pression semble prometteur et offre un environnement préexpansion plus agréable pour le patient.

A Novel, Deep Learning-Based, Automatic Photometric Analysis Software for Breast Aesthetic Scoring.

Background Breast aesthetics evaluation often relies on subjective assessments, leading to the need for objective, automated tools. We developed the Seoul Breast Esthetic Scoring Tool (S-BEST), a photometric analysis software that utilizes a DenseNet-264 deep learning model to automatically evaluate breast landmarks and asymmetry indices. Methods S-BEST was trained on a dataset of frontal breast photographs annotated with 30 specific landmarks, divided into an 80-20 training-validation split. The software requires the distances of sternal notch to nipple or nipple-to-nipple as input and performs image preprocessing steps, including ratio correction and 8-bit normalization. Breast asymmetry indices and centimeter-based measurements are provided as the output. The accuracy of S-BEST was validated using a paired t -test and Bland-Altman plots, comparing its measurements to those obtained from physical examinations of 100 females diagnosed with breast cancer. Results S-BEST demonstrated high accuracy in automatic landmark localization, with most distances showing no statistically significant difference compared with physical measurements. However, the nipple to inframammary fold distance showed a significant bias, with a coefficient of determination ranging from 0.3787 to 0.4234 for the left and right sides, respectively. Conclusion S-BEST provides a fast, reliable, and automated approach for breast aesthetic evaluation based on 2D frontal photographs. While limited by its inability to capture volumetric attributes or multiple viewpoints, it serves as an accessible tool for both clinical and research applications.

Finite element model of ocular adduction with unconstrained globe translation.

Details of the anatomy and behavior of the structures responsible for human eye movements have been extensively elaborated since the first modern biomechanical models were introduced. Based on these findings, a finite element model of human ocular adduction is developed based on connective anatomy and measured optic nerve (ON) properties, as well as active contractility of bilaminar extraocular muscles (EOMs), but incorporating the novel feature that globe translation is not otherwise constrained so that realistic kinematics can be simulated. Anatomy of the hemisymmetric model is defined by magnetic resonance imaging. The globe is modeled as suspended by anatomically realistic connective tissues, orbital fat, and contiguous ON. The model incorporates a material subroutine that implements active EOM contraction based on fiber twitch characteristics. Starting from the initial condition of 26° adduction, the medial rectus (MR) muscle was commanded to contract as the lateral rectus (LR) relaxed. We alternatively modeled absence or presence of orbital fat. During pursuit-like adduction from 26 to 32°, the globe translated 0.52 mm posteriorly and 0.1 mm medially with orbital fat present, but 1.2 mm posteriorly and 0.1 mm medially without fat. Maximum principal strains in the optic disk and peripapillary reached 0.05-0.06, and von-Mises stress 96 kPa. Tension in the MR orbital layer was ~ 24 g-force after 6° adduction, but only ~ 3 gm-f in the whole LR. This physiologically plausible simulation of EOM activation in an anatomically realistic globe suspensory system demonstrates that orbital connective tissues and fat are integral to the biomechanics of adduction, including loading by the ON.

Clinical implications of AR alterations in advanced prostate cancer: a multi-institutional collaboration.

BACKGROUND: AR gene alterations can develop in response to pressure of testosterone suppression and androgen receptor targeting agents (ARTA). Despite this, the relevance of these gene alterations in the context of ARTA treatment and clinical outcomes remains unclear. METHODS: Patients with castration-resistant prostate cancer (CRPC) who had undergone genomic testing and received ARTA treatment were identified in the Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) database. Patients were stratified according to the timing of genomic testing relative to the first ARTA treatment (pre-/post-ARTA). Clinical outcomes such as time to progression, PSA response, and overall survival were compared based on alteration types. RESULTS: In total, 540 CRPC patients who received ARTA and had tissue-based (n = 321) and/or blood-based (n = 244) genomic sequencing were identified. Median age was 62 years (range 39-90) at the time of the diagnosis. Majority were White (72.2%) and had metastatic disease (92.6%) at the time of the first ARTA treatment. Pre-ARTA genomic testing was available in 24.8% of the patients, and AR mutations and amplifications were observed in 8.2% and 13.1% of the patients, respectively. Further, time to progression was longer in patients with AR amplifications (25.7 months) compared to those without an AR alteration (9.6 months; p = 0.03). In the post-ARTA group (n = 406), AR mutations and AR amplifications were observed in 18.5% and 35.7% of the patients, respectively. The most common mutation in post-ARTA group was L702H (9.9%). CONCLUSION: In this real-world clinicogenomics database-driven study we explored the development of AR alterations and their association with ARTA treatment outcomes. Our study showed that AR amplifications are associated with longer time to progression on first ARTA treatment. Further prospective studies are needed to optimize therapeutic strategies for patients with AR alterations.

The Impact of Circulating Tumor Cell HOXB13 RNA Detection in Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated with Abiraterone or Enzalutamide.

PURPOSE: HOXB13 is an androgen receptor (AR) coregulator specifically expressed in cells of prostatic lineage. We sought to associate circulating tumor cell (CTC) HOXB13 expression with outcomes in men with mCRPC treated with abiraterone or enzalutamide. EXPERIMENTAL DESIGN: We conducted a retrospective analysis of the multicenter prospective PROPHECY trial of mCRPC men (NCT02269982, n = 118) treated with abiraterone/enzalutamide. CTC detection and HOXB13 complementary DNA (cDNA) expression was measured using a modified Adnatest, grouping patients into 3 categories: CTC 0 (undetectable); CTC+ HOXB13 CTC low (<4 copies); or CTC+ HOXB13 CTC high. The HOXB13 threshold was determined by maximally selected rank statistics for prognostic associations with overall survival (OS) and progression-free survival (PFS). RESULTS: We included 102 men with sufficient CTC HOXB13 cDNA, identifying 25%, 31%, and 44% of patients who were CTC 0, CTC+ HOXB13 low, and CTC+ HOXB13 high, respectively. Median OS were 25.7, 27.8, and 12.1 months whereas the median PFS were 9.0, 7.7, and 3.8 months, respectively. In subgroup analysis among men with CellSearch CTCs ≥5 copies/mL and adjusting for prior abi/enza treatment and Halabi clinical risk score, the multivariate HR for HOXB13 CTC detection was 2.39 (95% CI, 1.06-5.40) for OS and 2.78 (95% CI, 1.38-5.59) for PFS, respectively. Low HOXB13 CTC detection was associated with lower CTC PSA, PSMA, AR-FL, and AR-V7 detection, and more liver/lung metastases (41% vs. 25%). CONCLUSIONS: Higher CTC HOXB13 expression is associated with AR-dependent biomarkers in CTCs and is adversely prognostic in the context of potent AR inhibition in men with mCRPC.

Conserved chromatin and repetitive patterns reveal slow genome evolution in frogs.

Frogs are an ecologically diverse and phylogenetically ancient group of anuran amphibians that include important vertebrate cell and developmental model systems, notably the genus Xenopus. Here we report a high-quality reference genome sequence for the western clawed frog, Xenopus tropicalis, along with draft chromosome-scale sequences of three distantly related emerging model frog species, Eleutherodactylus coqui, Engystomops pustulosus, and Hymenochirus boettgeri. Frog chromosomes have remained remarkably stable since the Mesozoic Era, with limited Robertsonian (i.e., arm-preserving) translocations and end-to-end fusions found among the smaller chromosomes. Conservation of synteny includes conservation of centromere locations, marked by centromeric tandem repeats associated with Cenp-a binding surrounded by pericentromeric LINE/L1 elements. This work explores the structure of chromosomes across frogs, using a dense meiotic linkage map for X. tropicalis and chromatin conformation capture (Hi-C) data for all species. Abundant satellite repeats occupy the unusually long (~20 megabase) terminal regions of each chromosome that coincide with high rates of recombination. Both embryonic and differentiated cells show reproducible associations of centromeric chromatin and of telomeres, reflecting a Rabl-like configuration. Our comparative analyses reveal 13 conserved ancestral anuran chromosomes from which contemporary frog genomes were constructed.

Scanning Laser Ophthalmoscopy Demonstrates Pediatric Optic Disc and Peripapillary Strain During Horizontal Eye Rotation.

Purpose: We employed automated analysis of scanning laser ophthalmoscopy (SLO) to determine if mechanical strains imposed on disc, and retinal and choroidal vessels during horizontal duction in children differ from those of adults.Methods: Thirty-one children aged 11.3 ± 2.7 (standard deviation) years underwent SLO in central gaze, and 35° ab- and adduction. Automated registration with deep learning-based optical flow analysis quantified vessel deformations as horizontal, vertical, shear, and equivalent strains. Choroidal vessel displacements in lightly pigmented fundi, and central disc vessel displacements, were also observed.Results: As in adults, strain in vessels during horizontal duction was greatest at the disc and decreased with distance from it. Strain in the pediatric disc was similar to published values in young adults,1 but in the peripapillary region was greater and propagated significantly more peripherally to at least three disc radii from it. During adduction in children, the nasal disc was compressed and disc vessels distorted, but the temporal half experienced tensile strain, while peripapillary tissues were compressed. The pattern was similar but strains were less in abduction (p < .001). Choroidal vessels were visualized in 24 of the 62 eyes and shifted directionally opposite overlying retinal vessels.Conclusions: Horizontal duction deforms the normal pediatric optic disc, central retinal vessels, peripapillary retina, and choroid, shearing the inner retina over the choroid. These mechanical effects occur at the sites of remodeling of the disc, sclera, and choroid associated with typical adult features that later emerge later, including optic cup enlargement, temporal disc tilting, and peripapillary atrophy.

Evaluating the Surgical Outcome of Lymphovenous Anastomosis in Breast Cancer-Related Lymphedema Using Tc-99m Phytate Lymphoscintigraphy: Preliminary Results.

Background: Breast cancer-related lymphedema (BCRL) remains a significant postcancer treatment challenge with no definitive cure. Recent supermicrosurgical treatments, such as lymphovenous anastomosis (LVA), have shown promise but lack established objective indicators for outcome evaluation. We investigated the utility of Technetium-99m (Tc-99m) lymphoscintigraphy, an imaging technique providing objective information on lymphatic fluid flow, for assessing LVA surgical outcomes. Methods and Results: A retrospective cohort analysis of patients undergoing LVA for BCRL was conducted. Lymphoscintigraphy images pre- and 1-year postsurgery were compared to determine changes in lymphatic fluid flow of 18 patients based on newly defined parameters "uptake ratio" and "washout rates." Statistically significant reduction in the uptake ratio was observed in the forearm at 30 and 60 minutes postinjection phases. In addition, the forearm showed higher washout rate, indicating an improved lymphatic function in the forearm. Conclusion: Tc-99m lymphoscintigraphy can provide valuable objective data for evaluating LVA surgical outcomes in BCRL patients. However, site-specific differences in outcomes highlight the need for individualized surgical planning. Further large-scale studies are necessary to validate these preliminary findings and develop a standardized approach for LVA assessment.

Clinical, Radiographic, and Patient-Reported Outcomes of First Metatarsophalangeal Interposition Arthrodesis Using Porous Titanium Wedges.

BACKGROUND: First metatarsophalangeal (MTP) arthrodesis is a common surgical procedure for addressing hallux MTP pathology. In the setting of revision procedures with significant bone loss, porous titanium wedges may provide an alternative to structural bone autograft or allograft. OBJECTIVE: The purpose of this study is to report the clinical and radiographic outcomes achieved in first MTP interposition arthrodesis using porous titanium wedges. METHODS: A retrospective analysis of 9 patients with a mean age 65.4 years (45-82 years) who underwent first MTP interposition arthrodesis with the use of porous titanium wedges from February 2014 to September 2017 was performed. Outcomes were assessed using both plain-film radiographs and computed tomography (CT) scans, as well as patient-reported outcome measures, including Foot and Ankle Ability Measure (FAAM) (Sports and Activities of Daily Living), pain Visual Analogue Scale (VAS), and 36-Item Short Form Survey (SF-36). Average follow-up time was 34.2 months (14-72 months). RESULTS: At final follow-up, the average FAAM score was 91.1 ± 14.7 (75.1 ± 5.3 FAAM Activities of Daily Living; 17.9 ± 9.9 FAAM Sports). Average pain VAS score was 1.9 ± 1.7. Postoperative computed tomography (CT) imaging was obtained for 5 patients, all of which demonstrated good bony apposition or osseous integration of the wedge. Four patients underwent subsequent surgical procedures, including 3 isolated dorsal fixation revisions, and 1 complete MTP arthrodesis revision. CONCLUSION: To our knowledge, this study represents the first reported clinical and radiographic outcomes in patients undergoing first MTP interposition arthrodesis with use of porous titanium wedges. While we found this technique to be a viable alternative to bone grafting for this difficult problem, further research should focus on comparative data with other commonly performed operative techniques. LEVEL OF EVIDENCE: Level IV: Case series.

Diagnostic Accuracy of the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC): An Institution Experience.

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is a standardized system which is used to classify results of thyroid fine-needle aspiration (FNA). This system is used to evaluate and determine which patients should get thyroid surgery. It was created in order to reduce the number of patients requiring surgery. The question remains as to whether this reporting system is accurate in determining those nodules that have malignant potential and those that do not. This study is a retrospective analysis of patients in one institution who have undergone FNA and then thyroid surgery based on TBSRTC. The outcome of the pathology reports after surgery was analyzed to determine the accuracy of TBSRTC in our institution (Lourdes Hospital, Binghamton, NY). The results from our institution were compared with similar studies in other institutions to determine accuracy and reproducibility. Our results indicated that the risk of malignancy in each Bethesda category was similar to the risk percentages described for most categories in the 2017 TBSRTC update.