Characterization and Potential Relevance of Randomized Controlled Trial Patient Populations in Revision Total Joint Arthroplasty: A Systematic Review.

INTRODUCTION: Randomized controlled trial (RCT) studies in revision total joint arthroplasty (rTJA) are essential to investigate the effectiveness of interventions. However, there has been limited research investigating how patient cohorts comprising rTJA RCT samples resemble the US patient population undergoing rTJA in terms of demographic and clinical characteristics. Thus, the purpose of this systematic review was to compare the patient characteristics of rTJA RCT cohorts with the characteristics of national patient database cohorts. METHODS: RCT studies for rTJA were aggregated. Patient demographics in this group were compared against HCUP NIS and ACS-NSQIP patient cohorts. RESULTS: Forty-six RCTs met inclusion criteria. There were 3,780 total patients across 46 RCTs. The average age of patients in the rTJA RCT cohort was 66.4 9.4 while the NIS cohort was 67.3 11.1 (d=0.08, effect size=small). The average BMI of the rTJA RCT cohort was 31.1 5.7 while the NSQIP cohort was 31.7 8.3 (d=0.08, effect size=small). For rTJA, effect sizes for age, BMI, sex, ethnicity, smoking, and diabetes were all small or very small. CONCLUSIONS: Overall, the rTJA RCT patient cohort does not differ significantly compared to the general patient population undergoing rTJA. Differences in demographic and clinical characteristics between the rTJA RCT cohort and database cohorts were minimal to small, indicating that these differences are unlikely to impact clinical outcomes.

Molecular and functional landscape of malignant serous effusions for precision oncology.

Personalized treatment for patients with advanced solid tumors critically depends on the deep characterization of tumor cells from patient biopsies. Here, we comprehensively characterize a pan-cancer cohort of 150 malignant serous effusion (MSE) samples at the cellular, molecular, and functional level. We find that MSE-derived cancer cells retain the genomic and transcriptomic profiles of their corresponding primary tumors, validating their use as a patient-relevant model system for solid tumor biology. Integrative analyses reveal that baseline gene expression patterns relate to global ex vivo drug sensitivity, while high-throughput drug-induced transcriptional changes in MSE samples are indicative of drug mode of action and acquired treatment resistance. A case study exemplifies the added value of multi-modal MSE profiling for patients who lack genetically stratified treatment options. In summary, our study provides a functional multi-omics view on a pan-cancer solid tumor cohort and underlines the feasibility and utility of MSE-based precision oncology.

AKT and EZH2 inhibitors kill TNBCs by hijacking mechanisms of involution.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and has the highest rate of recurrence1. The predominant standard of care for advanced TNBC is systemic chemotherapy with or without immunotherapy; however, responses are typically short lived1,2. Thus, there is an urgent need to develop more effective treatments. Components of the PI3K pathway represent plausible therapeutic targets; more than 70% of TNBCs have alterations in PIK3CA, AKT1 or PTEN3-6. However, in contrast to hormone-receptor-positive tumours, it is still unclear whether or how triple-negative disease will respond to PI3K pathway inhibitors7. Here we describe a promising AKT-inhibitor-based therapeutic combination for TNBC. Specifically, we show that AKT inhibitors synergize with agents that suppress the histone methyltransferase EZH2 and promote robust tumour regression in multiple TNBC models in vivo. AKT and EZH2 inhibitors exert these effects by first cooperatively driving basal-like TNBC cells into a more differentiated, luminal-like state, which cannot be effectively induced by either agent alone. Once TNBCs are differentiated, these agents kill them by hijacking signals that normally drive mammary gland involution. Using a machine learning approach, we developed a classifier that can be used to predict sensitivity. Together, these findings identify a promising therapeutic strategy for this highly aggressive tumour type and illustrate how deregulated epigenetic enzymes can insulate tumours from oncogenic vulnerabilities. These studies also reveal how developmental tissue-specific cell death pathways may be co-opted for therapeutic benefit.

Integrating spatial profiles and cancer genomics to identify immune-infiltrated mismatch repair proficient colorectal cancers.

Predicting the progression of solid cancers based solely on genetics is challenging due to the influence of the tumor microenvironment (TME). For colorectal cancer (CRC), tumors deficient in mismatch repair (dMMR) are more immune infiltrated than mismatch repair proficient (pMMR) tumors and have better prognosis following resection. Here we quantify features of the CRC TME by combining spatial profiling with genetic analysis and release our findings via a spatially enhanced version of cBioPortal that facilitates multi-modal data exploration and analysis. We find that ∼20% of pMMR tumors exhibit similar levels of T cell infiltration as dMMR tumors and that this is associated with better survival but not any specific somatic mutation. These T cell-infiltrated pMMR (tipMMR) tumors contain abundant cells expressing PD1 and PDL1 as well as T regulatory cells, consistent with a suppressed immune response. Thus, like dMMR CRC, tipMMR CRC may benefit from immune checkpoint inhibitor therapy. SIGNIFICANCE: pMMR tumors with high T cell infiltration and active immunosuppression are identifiable with a mid-plex imaging assay whose clinical deployment might double the number of treatment-naïve CRCs eligible for ICIs. Moreover, the low tumor mutational burden in tipMMR CRC shows that MMR status is not the only factor promoting immune infiltration.

Multimodal Spatial Profiling Reveals Immune Suppression and Microenvironment Remodeling in Fallopian Tube Precursors to High-Grade Serous Ovarian Carcinoma.

High-Grade Serous Ovarian Cancer (HGSOC) originates from fallopian tube (FT) precursors. However, the molecular changes that occur as precancerous lesions progress to HGSOC are not well understood. To address this, we integrated high-plex imaging and spatial transcriptomics to analyze human tissue samples at different stages of HGSOC development, including p53 signatures, serous tubal intraepithelial carcinomas (STIC), and invasive HGSOC. Our findings reveal immune modulating mechanisms within precursor epithelium, characterized by chromosomal instability, persistent interferon (IFN) signaling, and dysregulated innate and adaptive immunity. FT precursors display elevated expression of MHC-class I, including HLA-E, and IFN-stimulated genes, typically linked to later-stage tumorigenesis. These molecular alterations coincide with progressive shifts in the tumor microenvironment, transitioning from immune surveillance in early STICs to immune suppression in advanced STICs and cancer. These insights identify potential biomarkers and therapeutic targets for HGSOC interception and clarify the molecular transitions from precancer to cancer. STATEMENT OF SIGNIFICANCE: This study maps the immune response in fallopian tube precursors of high-grade serous ovarian cancer, highlighting localized interferon signaling, CIN, and competing immune surveillance and suppression along the progression axis. It provides an explorable public spatial profiling atlas for investigating precancer mechanisms, biomarkers, and early detection and interception strategies.

Multiple gouty tophi in a six-year-old.

Introduction: Gouty tophus in a child is an extremely rare presentation. Only very few cases have been documented in literature in contemporary times. Case presentation: We present this index case of a 6-year-old child who was brought to the clinic by her parents on account of multiple subcutaneous swelling of two years' duration on her lower limbs before she presented at our outpatient clinic. The swellings started from the knee joints and were associated with difficulty in walking. A provisional diagnosis of multiple soft tissue swelling was made before some of the swellings were excised. An excisional biopsy of some of the masses on the lower extremities was done, and histological examination revealed gouty tophus. She was then placed on oral febuxostat. Her clinical condition has improved significantly; she is on continuous follow-up at our facility's paediatric orthopaedic outpatient clinic. Hitherto, gouty tophus has been recorded in juveniles and young adults, but it may present in any child below the age of five years. Conclusion: A high index of suspicion is needed in managing subcutaneous swellings in the paediatric age group (particularly pre-school) to identify and manage gouty tophus early enough to minimise its complications. Funding: None declared.

Carcinoplaxmistio Ng & Mitra, 2019 (Crustacea, Decapoda, Goneplacidae): additional records and genetic differentiation of allied taxa.

The goneplacid crab, Carcinoplaxmistio Ng & Mitra, 2019, was originally described from West Bengal, India, in the northern Indian Ocean. Additional material of C.mistio from off Tamil Nadu in the southeast of India revealed a high degree of size-associated variation in the structures of the anterolateral tooth of the carapace, chelipeds, and male and female pleons. In addition to an in-depth morphological examination of C.mistio, this study also records the natural coloration of the species and conducts a genetic comparison (with mitochondrial COI and 16S rRNA genes) with its close relatives, C.haswelli (Miers, 1884) and C.purpurea Rathbun, 1914. Molecular comparison of C.mistio with its morphologically closest congener, C.haswelli from northern Australia and the western Pacific, corroborates their status as separate species. The genetic sequence of C.mistio, however, is similar to that of C.purpurea from the West Pacific, although these two species can easily be distinguished by distinct carapace and ambulatory leg characters. The present study provides some possible explanations for the genetic and morphological incongruence observed between C.mistio and C.purpurea and highlights the need for a detailed molecular study for Carcinoplax H. Milne Edwards, 1852, to appreciate the evolution of various morphological characters in the genus.

Treatment of Acute Iatrogenic Cerebrovascular Injury Using Flow Diverter Stents.

BACKGROUND AND OBJECTIVES: Iatrogenic cerebrovascular injury can cause intracranial hemorrhage and pseudoaneurysm formation, putting patients at high risk for postoperative bleeding. No consensus for management exists. This study describes endovascular treatment of these acute injuries with flow diverter stents. METHODS: Electronic medical records were retrospectively reviewed for injury type and etiology, timing of diagnosis, and endovascular management, including antiplatelet regimens, embolization results, and clinical outcome. RESULTS: Six patients were included. Three suffered an injury to the internal carotid artery, 1 suffered an injury to the left anterior cerebral artery, 1 suffered an injury to the right posterior cerebral artery, and 1 suffered an injury to the basilar artery. Four of the 6 injuries occurred during attempted tumor resection, 1 occurred during cerebrospinal fluid leak repair, and 1 occurred during an ophthalmic artery aneurysm clipping. All injuries resulted in pseudoaneurysm formation. Four were immediately detected on angiography; 2 were initially negative on imaging. Five were treated with a pipeline embolization device, and 1 was treated with a Silk Vista Baby. Two were treated with 2 pipeline embolization devices telescopically overlapped across the pseudoaneurysm. All devices deployed successfully. No pseudoaneurysm recurrence or rebleeding occurred. No parent artery occlusion or stenosis was observed, and complete pseudoaneurysm occlusion was observed in 4 patients (in 2 patients, follow-up imaging could not be obtained). CONCLUSION: With proper antiplatelet regimens, flow diverter stents can be used safely to successfully treat complex acute iatrogenic injuries. Early repeat angiogram is needed when immediate postinjury imaging does not discover the point of vessel injury.

National introduction of one-anastomosis gastric bypass in the UK National Bariatric Surgery Registry - a cohort study.

AIM: There is a paucity of evidence regarding the national introduction of newer bariatric metabolic surgery procedures. This study assessed the impact of introducing one-anastomosis gastric bypass (OAGB) in bariatric surgical practice in the UK on 30-day postoperative morbidity and early postoperative weight loss. METHODS: Patients who underwent primary BMS in the UK National Bariatric Surgical Registry (2010-2019) were identified. Patient characteristics, 30-day postoperative morbidity, and 12-month total body weight loss (TBWL) were also assessed. Multivariate regression was performed for associations between 30-day postoperative morbidity and 12-month TBWL, with SG as a reference. Learning effects were assessed by factoring in the institutional OAGB caseload (0-24/25-49/50+ cases). RESULTS: A total of 59,226 patients underwent primary BMS during the study period (RYGB, 38,434; SG, 24,702; AGB, 12,627; OAGB, 3,408; and Others, 276). The 30-day postoperative morbidity was lower for OAGB 1.8% (51/2,802) compared to RYGB 4.2% (1,391/32,853) and SG 3.4% (725/21,333) but higher than AGB 1.2% (123/9,915), while on multivariate regression, OAGB was associated with reduced morbidity once the institution caseload exceeded 50 operations (OR 0.35 (95% CI, 0.22-0.56; P<0.001) and no statistical difference to SG at lesser caseloads. Overall, 12-month greater than 25% TBWL was seen in 69.4% (27736/39971) (RYGB: 82.9% (17617/21246)), SG: 65.4% (7383/11283)), AGB: 23.9% (1382/5572)) and OAGB: 82.9% (1328/1601)). On multivariate regression, OAGB was associated with the highest 12-month TBWL once the institution caseload exceeded 50 operations (OR 3.47 (95% CI 2.75-4.39; P<0.001). CONCLUSION: OAGB has been safely implemented in UK national bariatric surgery practice. It has lower reported postoperative morbidity and comparable weight loss to RYGB or SG, despite being offered to patients with more severe and complex obesity.

Reliability and validity of the Paprosky classification for acetabular bone loss based on level of orthopedic training.

BACKGROUND: Reliability and validity of the Paprosky classification for acetabular bone loss have been debated. Additionally, the relationship between surgeon training level and Paprosky classification accuracy/treatment selection is poorly defined. This study aimed to: (1) evaluate the validity of preoperative Paprosky classification/treatment selection compared to intraoperative classification/treatment selection and (2) evaluate the relationship between training level and intra-rater and inter-rater reliability of preoperative classification and treatment choice. METHODS: Seventy-four patients with intraoperative Paprosky types [I (N = 24), II (N = 27), III (N = 23)] were selected. Six raters (Residents (N = 2), Fellows (N = 2), Attendings (N = 2)) independently provided Paprosky classification and treatment using preoperative radiographs. Graders reviewed images twice, 14 days apart. Cohen's Kappa was calculated for (1) inter-rater agreement of Paprosky classification/treatment by training level (2), intra-rater reliability, (3) preoperative and intraoperative classification agreement, and (4) preoperative treatment selection and actual treatment performed. RESULTS: Inter-rater agreement between raters of the same training level was moderate (K range = 0.42-0.50), and mostly poor for treatment selection (K range = 0.02-0.44). Intra-rater agreement ranged from fair to good (K range = 0.40-0.73). Agreement between preoperative and intraoperative classifications was fair (K range = 0.25-0.36). Agreement between preoperative treatment selections and actual treatments was fair (K range = 0.21-0.39). CONCLUSION: Inter-rater reliability of Paprosky classification was poor to moderate for all training levels. Preoperative Paprosky classification showed fair agreement with intraoperative Paprosky grading. Treatment selections based on preoperative radiographs had fair agreement with actual treatments. Further research should investigate the role of advanced imaging and alternative classifications in evaluation of acetabular bone loss.

Explainable AI for computational pathology identifies model limitations and tissue biomarkers.

Deep learning models have shown promise in histopathology image analysis, but their opaque decision-making process poses challenges in high-risk medical scenarios. Here we introduce HIPPO, an explainable AI method that interrogates attention-based multiple instance learning (ABMIL) models in computational pathology by generating counterfactual examples through tissue patch modifications in whole slide images. Applying HIPPO to ABMIL models trained to detect breast cancer metastasis reveals that they may overlook small tumors and can be misled by non-tumor tissue, while attention maps-widely used for interpretation-often highlight regions that do not directly influence predictions. By interpreting ABMIL models trained on a prognostic prediction task, HIPPO identified tissue areas with stronger prognostic effects than high-attention regions, which sometimes showed counterintuitive influences on risk scores. These findings demonstrate HIPPO's capacity for comprehensive model evaluation, bias detection, and quantitative hypothesis testing. HIPPO greatly expands the capabilities of explainable AI tools to assess the trustworthy and reliable development, deployment, and regulation of weakly-supervised models in computational pathology.

Deep PSA response and extended time-to-nadir as robust predictors of survival in Asian patients with de novo metastatic hormone-sensitive prostate cancer receiving upfront intensified treatment.

INTRODUCTION: In de novo metastatic hormone-sensitive prostate cancer (mHSPC) treated with upfront intensification using androgen receptor signaling inhibitor or chemotherapy (Docetaxel), achieving a PSA nadir less than 0.2 ng/mL, indicative of superior survival in trials, may often be unattainable in real-world settings. We explored the predictive value of the degree of PSA decline and time to PSA nadir (TTPN) on oncological outcomes. METHODS: A prospectively maintained database of consecutive prostate cancer cases in Hong Kong was accessed. Patients diagnosed with de novo mHSPC from 2016 to 2022 and treated with upfront intensification were included in this analysis. Landmark analysis on PSA kinetics at 6-months following treatment intensification was performed. They were classified based on 1) TTPN (≥6 months vs. <6 months), and 2) a combined response (deep responders achieving both ≥95% PSA decline and TTPN ≥ 6 months vs. shallow responders). Multivariable regression analysis was employed to identify the effects of confounders. FINDINGS: A total of 131 patients were included in this analysis. Classifying patients by combined response best predicted survival outcomes. Deep responders had better progression-free survival (HR = 0.56; 95%CI = 0.34-0.91; p = 0.019), overall survival (HR = 0.50; 95%CI = 0.26-0.97; p = 0.036), and cancer-specific survival (HR = 0.43; 95%CI = 0.19-0.99; p = 0.042). Difference in overall survival remained significant after adjustment in multivariable regression analysis. CONCLUSION: Our analysis demonstrates that alternative PSA targets can predict treatment response and survival outcomes in de novo mHSPC patients in a real-world setting, providing valuable information for patient counselling and potentially guiding future trial design.

Integrative multiomic approaches reveal ZMAT3 and p21 as conserved hubs in the p53 tumor suppression network.

TP53 , the most frequently mutated gene in human cancer, encodes a transcriptional activator that induces myriad downstream target genes. Despite the importance of p53 in tumor suppression, the specific p53 target genes important for tumor suppression remain unclear. Recent studies have identified the p53-inducible gene Zmat3 as a critical effector of tumor suppression, but many questions remain regarding its p53-dependence, activity across contexts, and mechanism of tumor suppression alone and in cooperation with other p53-inducible genes. To address these questions, we used Tuba-seq Ultra somatic genome editing and tumor barcoding in a mouse lung adenocarcinoma model, combinatorial in vivo CRISPR/Cas9 screens, meta-analyses of gene expression and Cancer Dependency Map data, and integrative RNA-sequencing and shotgun proteomic analyses. We established Zmat3 as a core component of p53-mediated tumor suppression and identified Cdkn1a as the most potent cooperating p53-induced gene in tumor suppression. We discovered that ZMAT3/CDKN1A serve as near-universal effectors of p53-mediated tumor suppression that regulate cell division, migration, and extracellular matrix organization. Accordingly, combined Zmat3 - Cdkn1a inactivation dramatically enhanced cell proliferation and migration compared to controls, akin to p53 inactivation. Together, our findings place ZMAT3 and CDKN1A as hubs of a p53-induced gene program that opposes tumorigenesis across various cellular and genetic contexts.

Oncologic Outcomes of Incidental Versus Biopsy-diagnosed Grade Group 1 Prostate Cancer: A Multi-institutional Study.

Background and objective: Patients diagnosed with grade group (GG) 1 prostate cancer (PCa) following treatment for benign disease ("incidental" PCa) are typically managed with active surveillance (AS). It is not known how their outcomes compare with those observed in patients diagnosed with GG1 on biopsy. We aimed at determining whether long-term oncologic outcomes of AS for patients with GG1 PCa differ according to the type of diagnosis: incidental versus biopsy detected. Methods: A retrospective, multi-institutional analysis of PCa patients with GG1 on AS at eight institutions was conducted. Competing risk analyses estimated the incidence of metastases, PCa mortality, and conversion to treatment. As a secondary analysis, we estimated the risk of GG ≥2 on the first follow-up biopsy according to the type of initial diagnosis. Key findings and limitations: A total of 213 versus 1900 patients with incidental versus biopsy-diagnosed GG1 were identified. Patients with incidental cancers were followed with repeated biopsies and multiparametric magnetic resonance imaging less frequently than those diagnosed on biopsy. The 10-yr incidence of treatment was 22% for incidental cancers versus 53% for biopsy (subdistribution hazard ratio [sHR] 0.34, 95% confidence interval [CI] 0.26-0.46, p < 0.001). Distant metastases developed in one patient with incidental cancer versus 17 diagnosed on biopsy and were diagnosed with molecular imaging in 13 (72%) patients. The 10-yr incidence of metastases was 0.8% for patients with incidental PCa and 2% for those diagnosed on biopsy (sHR 0.35, 95% CI 0.05-2.54, p = 0.3). The risk of GG ≥2 on the first follow-up biopsy was low if the initial diagnosis was incidental (7% vs 22%, p < 0.001). Conclusions and clinical implications: Patients with GG1 incidental PCa should be evaluated further to exclude aggressive disease, preferably with a biopsy. If no cancer is found on biopsy, then they should receive the same follow-up of a patient with a negative biopsy. Further research should confirm whether imaging and biopsies can be avoided if postoperative prostate-specific antigen is low (<1-2 ng/ml). Patient summary: We compared the outcomes of patients with low-grade prostate cancer on active surveillance according to the type of their initial diagnosis. Patients who have low-grade cancer diagnosed on a procedure to relieve urinary symptoms (incidental prostate cancer) are followed less intensively and undergo curative-intended treatment less frequently. We also found that patients with incidental prostate cancer are more likely to have no cancer on their first follow-up biopsy than patients who have low-grade cancer initially diagnosed on a biopsy. These patients have a more favorable prognosis than their biopsy-detected counterparts and should be managed the same way as patients with negative biopsies if they undergo a subsequent biopsy that shows no cancer.

Central Hearing Loss in a Pediatric Patient.

Sensorineural hearing loss is typically caused by dysfunction of the inner ear or auditory nerve. In pediatric patients diagnosed with sensorineural hearing loss, work-up often includes genetic testing and imaging studies of the auditory pathway. Here, we report a case of a pediatric patient with a history of sensorineural hearing loss following cisplatin and radiation therapy for brainstem medulloblastoma, developing symptoms and signs of central hearing loss based on audiometric and MRI/diffusion tensor imaging studies. Though rare, central hearing loss should be considered among the causes of sensorineural hearing loss in children. Laryngoscope, 2024.

EFFICACY AND SAFETY OF THE PROPOSED BIOSIMILAR AFLIBERCEPT, SDZ-AFL, IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: 52-Week Results From the Phase 3 Mylight Study.

PURPOSE: The Phase 3 Mylight study was designed to confirm clinical equivalence of proposed biosimilar aflibercept (SOK583A1; Sandoz [proposed biosimilar aflibercept, SDZ-AFL]) to its reference biologic (Eylea; Regeneron Pharmaceuticals, Inc; Bayer AG [reference aflibercept, Ref-AFL]). METHOD: Mylight was a prospective, double-masked, 2-arm, parallel Phase 3 study. Participants with neovascular age-related macular degeneration were randomized 1:1 to receive eight injections of SDZ-AFL (n = 244) or Ref-AFL (n = 240) over 48 weeks. The primary endpoint was mean change in best-corrected visual acuity score from baseline to Week 8. Secondary endpoints included anatomical outcomes, best-corrected visual acuity at Weeks 24 and 52, safety, and pharmacokinetics. RESULTS: Similarity in mean change in best-corrected visual acuity score was established between SDZ-AFL (n = 235) and Ref-AFL (n = 226) at Week 8 (difference: -0.3 [90% CI, -1.5 to 1.0]) and Week 52. No clinically meaningful differences occurred between groups in anatomical outcomes. Safety profiles were similar, with comparable incidences of treatment-related adverse events (SDZ-AFL: 2.5%; Ref-AFL: 2.9%). The incidence of anti-drug antibodies was similar between groups. Systemic free aflibercept concentrations 24 hours postdose were low and comparable between SDZ-AFL and Ref-AFL. CONCLUSION: Proposed biosimilar aflibercept matched reference aflibercept in efficacy, safety, and pharmacokinetics in participants with neovascular age-related macular degeneration. Therefore, this Phase 3 study confirmed biosimilarity of SDZ-AFL to Ref-AFL.

Artificial Intelligence Analysis of Periorbital Rejuvenation.

BACKGROUND: Periorbital rejuvenation surgery aims to restore a youthful appearance to the face. Despite the popularity of these procedures, few objective measurements exist to evaluate their impact on perceived facial aging. OBJECTIVES: This study aims to quantify the impact of brow lift and blepharoplasty on age as perceived by convolutional neural network (CNN) algorithms. METHODS: A retrospective review was performed on patients who underwent upper blepharoplasty, lower blepharoplasty, and/or brow lift at a single cosmetic practice between 2018 and 2023. Collected data included patient demographics, procedure performed, fat pad resection, and pre- and postoperative frontal images. Each photo was analyzed by four artificial intelligence (AI) platforms to estimate the change in perceived age following surgery. The estimated age reduction was compared between procedures. RESULTS: Of the 153 included patients, 118 underwent blepharoplasty, 12 underwent brow lift, and 23 had both blepharoplasty and brow lift. Across all AI platforms, the mean age estimation percent error was 10.6%, with a tendency for AI to underestimate compared to true age. Univariate analysis revealed an age reduction following any surgery of 1.03 years (p<0.001). When controlling for other variables, brow lift patients saw a mean age reduction of 1.432 years (p=0.031). Upper and lower blepharoplasty, patient characteristics, and ancillary procedures were not found to be independently associated with significant age reduction. CONCLUSIONS: Brow lifts provide significant reduction in perceived age. When planning for periorbital rejuvenation, a thorough preoperative evaluation should be performed, and additional consideration should be given to brow lifting procedures.

Craters on the melanoma surface facilitate tumor-immune interactions and demonstrate pathologic response to checkpoint blockade in humans.

Immunotherapy leads to cancer eradication despite the tumor's immunosuppressive environment. Here, we used extended long-term in-vivo imaging and high-resolution spatial transcriptomics of endogenous melanoma in zebrafish, and multiplex imaging of human melanoma, to identify domains that facilitate immune response during immunotherapy. We identified crater-shaped pockets at the margins of zebrafish and human melanoma, rich with beta-2 microglobulin (B2M) and antigen recognition molecules. The craters harbor the highest density of CD8 + T cells in the tumor. In zebrafish, CD8 + T cells formed prolonged interactions with melanoma cells within craters, characteristic of antigen recognition. Following immunostimulatory treatment, the craters enlarged and became the major site of activated CD8 + T cell accumulation and tumor killing that was B2M dependent. In humans, craters predicted immune response to ICB therapy, showing response better than high T cell infiltration. This marks craters as potential new diagnostic tool for immunotherapy success and targets to enhance ICB response.

Early Recovery Outcomes in Patients Undergoing Contemporary Posterior Approach Total Hip Arthroplasty: Each Week Shows Progress.

Background: Little is known about patients' postoperative week-by-week progress after undergoing posterior approach total hip arthroplasty (THA) with regard to pain, function, return to work, and driving. Purpose: We sought to evaluate a large cohort of patients undergoing posterior approach THA with modified posterior hip precautions to better understand the trajectory of recovery. Methods: Patients at a single institution undergoing primary posterior approach THA by fellowship-trained arthroplasty surgeons were prospectively enrolled. Patient functional status and early rehabilitation recovery milestones were evaluated preoperatively and each week postoperatively for 6 weeks. Results: Of 312 patients who responded to weekly questionnaires, there were varying response rates per question. At 1 week after surgery, 15% (39/256) of respondents had returned to work, increasing to 57% (129/225) at week 6. At 6 weeks, 77% of patients (174/225) had returned to driving; 25% (56/225) were taking pain medication (including prescription opioids or nonsteroidal anti-inflammatory drugs); and 15% (34/225) were using assistive devices (down from 91%, 78%, 56%, 35%, and 27% at weeks 1, 2, 3, 4, and 5, respectively). Average postoperative Hip dysfunction and Osteoarthritis Outcome Score for Joint Replacement and Lower Extremity Functional Scale scores were significantly higher than preoperative scores. Respondents reported significantly less pain at each week postoperatively than the previous week. Conclusion: These findings suggest that there may be an expected pathway for recovery after posterior THA using perioperative pain protocols, modified postoperative precautions, and physical therapy protocols to improve patient outcomes after THA, with most patients returning to normal at 4 weeks. Defining the expected recovery timeline may help surgeons in counseling patients preoperatively and guiding their recovery.

Optical Properties and Growth Characteristics of 8-Quinolinolato Lithium (Liq) Nano-Layers Deposited by Gas Transport Deposition.

Organometallic complexes containing reactive alkali metals, such as lithium (Li), represent a promising material approach for electron injection layers and electron transport layers (EILs and ETLs) to enhance the performance of Organic Light-Emitting Diodes (OLEDs). 8-Quinolinolato Lithium (Liq) has shown remarkable potential as an EIL and ETL when conveyed in very thin films. Nevertheless, the deposition of nano-layers requires precise control over both thickness and morphology. In this work, we investigate the optical properties and morphological characteristics of Liq thin films deposited via Organic Vapor Phase Deposition (OVPD). Specifically, we present our methodology for analyzing the measured pseudodielectric function <ε(ω)> using Spectroscopic Ellipsometry (SE), alongside the nano-topography of evaporated Liq nano-layers using Atomic Force Microscopy (AFM). This information can contribute to the understanding of the functionality of this material, since ultra-thin Liq interlayers can significantly increase the operational stability of OLED architectures.