Citations

Background: Acetabular overcoverage (pincer morphology) has been suggested to be both a source of pain and dysfunction and potentially protective against osteoarthritic change. Purpose: To compare the minimum 5-year clinical outcomes of patients undergoing primary hip arthroscopic labral repair with a lateral center edge angle (LCEA) of ≥40° as compared with nondysplastic controls with an LCEA of 25° to 40°. Study Design: Cohort study; Level of evidence, 3. Methods: A retrospective review was performed to identify all patients who underwent primary hip arthroscopic labral repair between 2009 and 2019 at a single academic institution. Patients with an LCEA of ≥40° (pincer) were propensity-matched to nondysplastic controls with an LCEA of 25° to 40° on a 1-to-2 basis by sex, age, body mass index, and surgery year. Patient-reported outcome measures (PROMs)—including visual analog scale, Tegner activity score, modified Harris Hip Score, International Hip Outcome Tool (iHOT-12), and Hip Outcome Score were analyzed—as were reoperations and conversions to total hip arthroplasty (THA). Results: A total of 55 patients with pincer morphology (preoperative LCEA: 41.9°± 2.1°) were matched to 110 nondysplastic controls (LCEA: 31.2°± 4.1°), resulting in a total of 165 hips in 163 patients (67% women, mean age: 37.7 ± 9 years). Pincer patients were corrected to a mean postoperative LCEA of 38.7°± 4.1º ( P < .001), with 22 pincer patients having residual overcoverage; namely, a postoperative LCEA ≥40° (range, 40°-45.8°). There were no differences between cohorts regarding intraoperative characteristics—including femoral and acetabular Outerbridge grade—as well as capsulotomy type and the presence of capsular repair ( P ≥ .210). At a mean 8-year follow-up (range, 5.1-13.2), there was no difference in any postoperative PROMs between pincers and controls ( P ≥ .215) and no difference in PROMs between patients with residual overcoverage and pincer patients with a postoperatively normalized LCEA ( P ≥ .291). At final follow-up, 4 patients in the pincer cohort (7%) and 21 controls (19%) converted to THA ( P = .046). Conclusion: Patients with lateral acetabular overcoverage demonstrated similar and satisfactory postoperative PROMs at a minimum 5-year follow-up compared with propensity-matched nondysplastic controls, regardless of whether the LCEA was corrected to <40°. Of note, nondysplastic controls demonstrated a higher rate of conversion to THA, suggesting a potentially chondroprotective role for acetabular overcoverage.

Abstract Repetitive head impacts sustained during American football have been associated with neuropathological changes such as white matter shear injuries. However, the impact of specific factors, such as age of first exposure and cumulative head impact burden, on white matter integrity remains unclear. This study investigated in vivo white matter microstructural changes using diffusion tensor imaging and tract-based spatial statistics in 165 male former American football players (mean age 57.3 years, range 45–74) and 52 unexposed asymptomatic male controls (mean age 59.4 years, range 45–74) in the DIAGNOSE CTE Research Project. Compared to controls, former football players exhibited significantly higher fractional anisotropy (FA) in 1.97% of the white matter skeleton (1552 voxels; Cohen’s d = 0.587) and higher tissue-corrected FA (FAt) in 1.48% of the white matter skeleton (1004 voxels; Cohen’s d = 0.616). No significant differences were observed for mean diffusivity, axial diffusivity, radial diffusivity, or free water between football players and controls. Among football players, there were no significant differences in the white matter microstructure between players diagnosed with traumatic encephalopathy syndrome and those without the diagnosis. Lower FA was significantly associated with older age (P &lt; 0.00001) and an earlier age of first exposure to tackle football (P &lt; 0.01), while lower FAt was associated with greater cumulative head impact burden, specifically higher linear acceleration (P &lt; 0.04) and rotational force (P &lt; 0.02). This study highlights the influential role of exposure factors on white matter microstructure in former American football players, as well as the utility of diffusion tensor imaging to aid in characterizing the long-term effects of repetitive head impacts in contact sport athletes.

Abstract Background Markerless tumor tracking (MTT) using single‐energy (SE) kilovoltage (kV) imaging has been proposed as a technique for lung tumor motion management. However, bony structures can obscure the tumor and make tracking challenging. Dual‐energy (DE) subtraction imaging can suppress the bone and therefore enhance tumor visibility, potentially improving tracking accuracy. Purpose To develop a machine learning model that predicts the reliability of MTT for SE and DE imaging using phantom and patient data. Methods Images were collected at high and low energy (120/60 kV) using fast‐kV switching on dynamic thorax phantom with 5–15 diameter targets and 20 lung cancer patients, including one patient with two tumor locations. DE images were then generated off‐line using weighted logarithmic subtraction. Separately, a template‐based tracking algorithm was used to track the tumor on both phantom and patient images. For phantom data, the ground truth (GT) was defined by the cos 4 waveform programmed into the motion controller. Since the GT was unknown for patient data, it was estimated using a Kalman filter and further refined using visual inspection. The tracking success rate (TSR) was subsequently calculated. Based on TSR, patients were stratified into three tracking groups: good, moderate, and poor. A logistic regression (LR) model was implemented with tracking features, including match score, peak to side‐peak ratio (PSR), x ‐ and y ‐velocity. To address the distribution differences between phantom and patient data, a domain indicator and interaction features were also incorporated. The model was trained on phantom and 17 patient data using leave‐one‐out cross‐validation, and its performance was evaluated on three held‐out patients, one from each tracking group. Separate LR models were developed for each imaging modality, resulting in SE‐LR and DE‐LR models. For each held‐out patient, the confusion matrix, sensitivity, and specificity were reported. Results For both SE‐LR and DE‐LR models, PSR has the largest coefficient value, indicating that it is the most influential factor when determining the reliability of tracking. At a specificity of 95%, the DE‐LR model achieved significantly higher sensitivity than the SE‐LR model (0.908 vs. 0.731, p < 0.01 for phantom data and 0.657 vs. 0.589, p < 0.01 for patient data). In the three held‐out patients, the DE‐LR model outperformed the SE‐LR model across all metrics. The largest gains were found in the patient with good tracking quality. Conclusions The proposed LR models successfully predicted the reliability of SE‐ and DE‐MTT. Across phantom and patient datasets, the DE‐LR model consistently demonstrated improved performance compared with the SE‐LR model, suggesting that DE imaging may be beneficial for MTT applications.

An exhalation delivery system for fluticasone (EDS-FLU) is designed to deposit drug into sinonasal regions above the inferior turbinate, particularly sinus drainage pathways not reached by standard nasal steroid sprays. We evaluated the efficacy and safety of EDS-FLU for chronic rhinosinusitis (CRS). We reviewed four independent randomized controlled trials derived from three published articles identified through searches of PubMed, Embase, SCOPUS, Google Scholar, Web of Science, and the Cochrane Library up to April 2024. Outcomes included 22-item Sinonasal Outcome Test (SNOT-22) scores, nasal symptom scores, nasal polyp scores, patient global impression of change (PGIC), responder and surgical indication rates, and adverse events. Compared with EDS-placebo, EDS-FLU produced greater reductions in nasal polyp scores and SNOT-22 scores over 6 months. At 3 months, nasal congestion, facial pain, rhinorrhea, and olfactory dysfunction improved more with EDS-FLU, and PGIC responder and complete response rates were higher at 3 and 6 months. EDS-FLU reduced surgical indication and increased overall responder rates at 3 months but not at 6 months. Epistaxis and nasal septal erosion or ulceration occurred more frequently with EDS-FLU, whereas rates of headache, nasal congestion, nasopharyngitis, and upper respiratory infection were similar between groups. EDS-FLU provides clinically meaningful improvements in subjective and objective outcomes in CRS but is associated with an increased risk of local nasal adverse events, warranting individualized risk-benefit assessment.

Abstract Spatial transcriptomics links gene expression to tissue architecture, providing a mechanistic view of cellular organization. Yet existing datasets cover few donors and miss the complexity of human disease. Experimental costs remain prohibitive, and large-scale profiling is impractically slow for population-level studies. Accurate computational methods are urgently needed. Predicting gene expression from standard histology, however, remains an open problem, as current approaches transfer poorly to unseen cohorts and diseases. Here, we present Phoenix, a (latent) flow matching generative model that infers pan-cancer spatially resolved single-cell gene expression with high accuracy. Phoenix analyzes treatment response in silico: Applied to 763 head and neck cancer patients, it identified three new spatial biomarkers that we validated across two cancers (breast cancer, n = 84; ovarian cancer, n = 157) and treatment regimens (platinum, trastuzumab). Phoenix generalizes beyond carcinomas: In a large sarcoma cohort (802 tissue microarray cores), it accurately predicted cell-type-specific signatures in held-out samples and captured chemotherapy-induced immune remodeling. Phoenix also extends across species: In a mouse model, it accurately predicted the expression of pancreatic cancer lineage markers and the mutant mKras^G12D allele in silico. In total, we evaluated Phoenix on over 10,000 patients. Our results establish virtual spatial transcriptomics as a scalable framework for studying tissue organization, therapeutic response, and disease mechanisms.

Importance Seizure-induced brain injury is central to the treatment urgency of new-onset refractory status epilepticus (NORSE). Identifying biomarkers that reflect ongoing neuronal damage could inform therapeutic timing and improve outcomes. Objective To quantify acute brain injury in patients with cryptogenic NORSE (cNORSE), etiology-defined status epilepticus (eSE), and chronic epilepsy. Design, Setting, and Participants This was an international cross-sectional study conducted between 2013 and 2025. Patients were enrolled at 36 hospitals in the US, 2 in Canada, and 1 in Italy, France, and Belgium. Patients with cNORSE and eSE for which biological samples were obtained during ongoing seizure activity were enrolled in the study. Comparison groups without status epilepticus comprised individuals with chronic epilepsy and healthy participants. None were excluded. Exposures Neurofilament light chain (NfL) and S100-beta (S100B) protein concentrations in serum and cerebrospinal fluid (CSF). Main Outcomes and Measures Degree of neuronal and glial damage, indexed by NfL and S100B levels, and their association with short-term functional outcomes. Results A total of 78 patients with cNORSE (mean [95% CI] age, 37 [30-41] years; 44 female [56%]) and 2 independent cohorts of 211 patients (mean [95% CI] age, 69 [66-71] years; 128 female [61%]) and 73 patients (mean [95% CI] age, 56 [45-65] years; 39 male [53%]) with eSE were included. NfL concentrations were markedly elevated in cNORSE—approximately 10-fold higher in CSF and 4-fold higher in serum—compared with the eSE cohorts (CSF: median [IQR], 6408 [1503-22 963] pg/mL compared with 694 [219-2389] pg/mL; serum: median [IQR], 231 [99-855] pg/mL compared with 55 [20-135] pg/mL; P &amp;lt;.001). Serum NfL levels were nearly 20-fold higher in cNORSE than in the cohort with epilepsy and in healthy controls (median [IQR], 11 [7-19 ] and 7 [5-14 ] pg/mL, respectively). Serum and CSF NfL levels were strongly correlated (Spearman ρ = 0.75; P &amp;lt; .001) and rose sharply between week 1 (median [IQR], 101 [51-137] pg/mL), week 2 (median [IQR], 197 [117-324] pg/mL), and week 3 (median [IQR], 598 [163-1000] pg/mL) after onset ( P &amp;lt; .001). In contrast, S100B concentrations did not differ between groups and showed no consistent temporal pattern. NfL discriminated cNORSE from eSE (area under the receiver operating characteristic curve [AUROC], 0.79; 95% CI, 0.68-0.90) and from cohorts without status epilepticus (AUROC, 0.99; 95% CI, 0.78-1.00). Higher serum NfL was independently associated with poor functional outcome at discharge (Glasgow Outcome Scale extended score, 1-4; odds ratio, 1.01; 95% CI, 1.00-1.03; P = .03). Conclusions and Relevance Results of this cross-sectional study suggest that acute neuroaxonal injury, as reflected by elevated NfL levels, was substantially greater in cNORSE than in the cohorts with eSE and in controls without status epilepticus. The rapid early rise in NfL highlights a narrow therapeutic window, emphasizing the need for prompt, effective, and potentially neuroprotective interventions in cNORSE.

ABSTRACT Immediate early genes (IEGs) encode master transcription factors, including EGR1 , FOS , JUN , and MYC genes that drive robust transcription in the G1 phase of cell cycle. Our previous studies indicate that topoisomerase IIβ (TOP2B) critically regulates IEG transcription and that the activities of TOP2B are dynamically controlled through post-translational modifications by BRCA1-BARD1 and ERKs. Here, we show that two E2 enzymes, UBCH5b and UBC13/MMS2, differentiate the effects and functions of TOP2B ubiquitination by BRCA1-BARD1. Comprehensive transcriptomics, proteomics, and biochemical and molecular cellular analyses revealed a close relationship between BARD1 and key mitogen-activated protein kinase pathway genes and identified activated ERK2 as a novel kinase that phosphorylates BARD1 at S391, a previously reported mitotic phosphorylation site, whose genetic mutation has been linked to tumorigenesis. Mechanistically, the catalytic activity of ERK2 stimulates TOP2B ubiquitination mediated by BRCA1-BARD1 in complex with UBCH5b and UBC13/MMS2, which controls the binding and function of TOP2B and BARD1 for transcriptional activation at representative IEGs. Taken together, our data propose that there is a functional regulatory circuit involving TOP2B, BARD1, and ERK2, three key transcriptional activators for IEG transcription, in which the gene association and catalytic activity of TOP2B are regulated through E2-differentiated ubiquitination by BRCA1-BARD1 and the phosphorylation of BARD1 by ERK2 for productive transcription.

ABSTRACT Background Journal clubs provide opportunities for discussion of new and evolving practices and technologies. Objective We sought to evaluate the utility and effectiveness of a monthly web‐based cosmetic dermatology journal club facilitated by faculty, residents, and medical students. Results From May 2025 to September 2025, 16 articles were discussed and 41 responses were recorded (response rate: 60%). Most respondents found the journal club was an appropriate length, engaging, and very useful. Relevance, frequency, and likelihood to participate in the future varied significantly by participant type. Medical students and residents collectively considered the journal club too infrequent ( p = 0.03) and reported it had less relevance to their practice ( p < 0.001). Conclusion A monthly web‐based cosmetic dermatology journal club was generally positively received by respondents.