Outcomes of centrally versus laterally based tarsoconjuctival pedicle flap reconstruction for large full thickness lower eyelid defects.

BACKGROUND: To compare the outcomes of two types of tarsoconjunctival pedicle flaps for reconstruction of large lower eyelid defects. METHODS: Retrospective medical record review of consecutive patients who underwent centrally-based or laterally-based tarsoconjunctival pedicle transconjunctival flap for lower eyelid reconstruction for defects greater than 50% of the lid margin. Full thickness skin grafts were used for anterior lamellar reconstruction in all cases. The primary outcome measure was eyelid position, function and satisfactory cosmesis. RESULTS: Forty-three patients were identified. Twenty-six patients underwent reconstruction with a centrally-based tarsoconjunctival pedicle flap; 17 patients underwent reconstruction with a laterally-based tarsoconjunctival pedicle flap. The average size of the lid defect was 77.7% (range 50-100%) in the central group and 75% (range 50-100%) in the lateral group (p=0.604). Mean follow up time was 61.5 weeks in the central group and 46.6 weeks in the lateral group (p=0.765). After division of the flap and during follow up, 27% of the centrally based group required revisional surgery with none in the laterally based group (p=0.03). 100% of the patients with centrally based flaps required second staged division of flap, whereas only 52% of patients with a laterally based flaps underwent second staged flap division. (p<0.001). CONCLUSION: Outcome suggests that for reconstruction of large lower lid defects requiring lid sharing procedures, both centrally and lateral-based procedures have equivalent functional outcome. However, the laterally based group has less need for revisional procedures and may not need a second stage division of the flap.

Effects of Teprotumumab on Eyelid Retraction in Thyroid Eye Disease.

PURPOSE: This study evaluates the efficacy of teprotumumab in reducing eyelid retraction in thyroid eye disease (TED) patients. METHODS: This retrospective study included patients with active or chronic moderate-to-severe TED who completed at least 4 cycles of teprotumumab. Patients with upper and/or lower eyelid retraction, defined as margin-to-reflex distance (MRD) 1 and/or MRD2 of more than 5 mm, in one or OU were included. The main outcome measure was a change in MRD1 and MRD2 after treatment. Changes in MRD1 and MRD2 were each analyzed for correlation (r) with changes in exophthalmolmetry. Student t test was performed for each comparison, and p values <0.05 were considered significant. RESULTS: The study included 91 patients, predominantly female (87%), with an average age of 52.02 ± 14.6 years. The mean baseline proptosis measurement was 21.8 ± 2.9 OD and 21.7 ± 3.3 OS. The average MRD1 was 5.5 ± 1.5 OD and 5.4 ± 1.7 OS, and the average MRD2 was 6.1 ± 1.1 OD and 6.2 ± 1.1 OS. The follow-up duration post-treatment was 37.5 ± 31.7 weeks. At first follow-up post-treatment, the mean change in proptosis, MRD1, and MRD2 were -2.6 ± 2.0 OD, -2.5 ± 2.1 OS, -0.8.5 ± 1.4 OD, -0.8 ± 1.0 OS, and -0.7 ± 0.9 OD, -0.8 ± 1.0 OS, respectively. Correlation analysis showed that proptosis reduction was positively correlated with MRD1 and MRD2 reduction at the first post-treatment follow-up (MRD1: r = 0.23, p value < 0.01; MRD2: r = 0.17, p = 0.03]. CONCLUSION: Teprotumumab treatment improves upper and lower eyelid retraction. The improvement in MRD correlated positively with proptosis reduction, indicating the influence of globe position on eyelid position.

Proportion of Angle Closure Glaucoma in Tamale, Ghana.

PRCIS: In the largest clinic-based study to date, our review of 588 patients presenting with glaucoma in Northern Ghana revealed 36% of these had primary angle closure glaucoma. PURPOSE: Glaucoma is the second leading cause of blindness worldwide. In Africa, glaucoma is an established public health problem, and primary angle-closure glaucoma (PACG) is not commonly discussed. Recognizing it is important because of its negative impact on visual morbidity, and also because its treatment is different from primary open angle glaucoma (POAG). In response to the observation of many PACG cases at the Northern Community Eye Hospital in Tamale, Ghana, we investigated the proportion of those attending with a first diagnosis of glaucoma who had PACG. PATIENTS AND METHODS: Using the electronic records, we identified 976 patients who attended with a first diagnosis of glaucoma between January 2021 and October 2022. Of these, 588 met the inclusion criterion of a clear glaucoma subtype diagnosis. RESULTS: Of these 316 (53.7%) had POAG, 210 (35.7%) PACG, and 62 (10.5%) secondary glaucoma. Thus, over a third of presenting glaucomas had PACG. CONCLUSION: This study highlights that PACG is present in about a third of patients presenting to our clinic in North Ghana . Our study demonstrates the importance of a clear diagnostic pathway including gonioscopy in the assessment of glaucoma patients and the consideration of wider training on angle closure glaucoma diagnosis and management.

Outcomes in Hematopoietic Cell Transplant and Chimeric Antigen Receptor T Cell Therapy Recipients with Pre-Cellular Therapy SARS-CoV-2 Infection.

BACKGROUND: Hematopoietic cell transplant (HCT) or chimeric antigen receptor T cell (CAR-T) therapy recipients have high morbidity from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. There are limited data on outcomes from SARS-CoV-2 infection shortly before cellular therapy and uncertainty whether to delay therapy. METHODS: We conducted a retrospective cohort study of patients with SARS-CoV-2 infection within 90 days prior to HCT or CAR-T therapy between January 2020 and November 2022. We characterized the kinetics of SARS-CoV-2 detection, clinical outcomes following cellular therapy, and impact on delays in cellular therapy. RESULTS: We identified 37 patients (n=15 allogeneic HCT, n=11 autologous HCT, n=11 CAR-T therapy) with SARS-CoV-2 infections within 90 days of cellular therapy. Most infections (73%) occurred between March and November 2022, when Omicron strains were prevalent. Most patients had asymptomatic (27%) or mild (68%) coronavirus disease 2019 (COVID-19). SARS-CoV-2 positivity lasted a median of 20.0 days [IQR, 12.5-26.25]. The median time from first positive SARS-CoV-2 test to cellular therapy was 45 days [IQR, 37.75-70]; one patient tested positive on the day of infusion. After cellular therapy, no patients had recrudescent SARS-CoV-2 infection or COVID-19-related complications. Cellular therapy delays related to SARS-CoV-2 infection occurred in 70% of patients for a median of 37 days. Delays were more common after allogeneic (73%) and autologous (91%) HCT compared to CAR-T cell therapy (45%). CONCLUSIONS: Patients with asymptomatic or mild COVID-19 may not require prolonged delays in cellular therapy in the context of contemporary circulating variants and availability of antiviral therapies.

Is Blepharoplasty Cost-effective? Utility Analysis of Dermatochalasis and Cost-effectiveness Analysis of Upper Eyelid Blepharoplasty.

PURPOSE: This cross-sectional prospective study measured utility values of upper eyelid dermatochalasis to quantify its impact on quality of life and assess cost-effectiveness of upper blepharoplasty. METHODS: Utility of dermatochalasis was assessed using the standard reference gamble and time trade-off methods, with dual anchor points of perfect eye function and perfect health. The utility value obtained was used to create a Markov model and run a cost-effectiveness analysis of blepharoplasty as a treatment for dermatochalasis while utilizing the societal perspective. RESULTS: One hundred three patients with dermatochalasis recruited from an urban outpatient ophthalmology clinic completed the utility survey. The authors determined utility values for dermatochalasis ranging from 0.74 to 0.92 depending on the measurement method (standard reference gamble/time trade-off) and anchor points. The cost-effectiveness analysis yielded an incremental cost-effectiveness ratio of $3,146 per quality-adjusted life year, well under the conventional willingness-to-pay threshold of $50,000 per quality-adjusted life year. Probabilistic sensitivity analysis with Monte Carlo simulation demonstrated that blepharoplasty would be cost-effective in 88.1% of cases at this willingness-to-pay threshold. CONCLUSIONS: Dermatochalasis has an impact on quality of life that is significantly associated with level of perceived functional impairment. Rising health care costs have underscored the importance of providing value-based treatment to patients, and the results of this study suggest that blepharoplasty is a cost-effective treatment option for symptomatic bilateral upper eyelid dermatochalasis.

Hemodynamic Renal Reserve Response in Conscious Normotensive and Hypertensive Mice.

INTRODUCTION: Renal function may be compromised following recovery from kidney insults. Renal functional reserve (RFR) is a measure of the difference between the kidney's maximum capacity and its baseline function, which helps identify any areas of the kidney with compromised function. Usually, RFR is evaluated using acute volume expansion (AVE), but this is typically done in anesthetized animals, which may not accurately represent the kidney's complete functional capacity. In this study, we have introduced a novel method that enables AVE to be conducted in conscious mice. METHODS: We have implemented this innovative approach in two animal models representing either intact or impaired renal function, specifically utilizing a lower nephron hypertensive model. Mice were implanted with radio-transmitters for mean artery blood pressure (MAP) monitoring during the experiment. After recovery, half of the mice were induced hypertension by right kidney nephrectomy combined with the ligation of the upper branch of the left kidney. For the AVE, a volume equivalent to 5% of the mouse's body weight was administered via intravenous (IV) or intraperitoneal bolus injection. Subsequently, the mice were individually housed in cages covered with plastic wrap. Urine was collected every hour for a total of 3 h for the measurement of urine and sodium excretion. RESULTS: The MAPs for all normotensive mice were consistent throughout the AVE, but it increased 5-16 mm Hg in the hypertensive mice upon AVE. Remarkably, conscious mice exhibited a significantly stronger response to IV-administered AVE when compared to anesthetized mice. This response was evident in the increase in urinary flow, which was approximately 170% and 145% higher in conscious normotensive and hypertensive mice, respectively, compared to their respective baselines. In contrast, anesthetized normotensive and hypertensive mice showed only around a 130% and 100% increase in urinary flow, respectively. Additionally, upon AVE, conscious normotensive mice excreted approximately 47% more sodium than conscious hypertensive mice. In contrast, anesthetized normotensive mice excreted only about 30% more sodium than their anesthetized hypertensive counterparts. CONCLUSION: Performing a kidney stress test with a significant solution load in conscious mice seems to be a superior method for evaluating RFR compared to conducting the test under anesthesia. Assessing kidney clearance while the mice are conscious has the potential to enhance the precision of diagnosing and predicting both acute and chronic kidney diseases.

In Search of the Truth: Choice of Ground-Truth for Predictive Modeling of Trauma Team Activation in Pediatric Trauma.

BACKGROUND: Assigning trauma team activation levels for trauma patients is a classification task that machine learning models can help optimize. However, performance is dependent upon the "ground-truth" labels used for training. Our purpose was to investigate two ground-truths, the Cribari matrix and the Need for Trauma Intervention (NFTI), for labeling training data. STUDY DESIGN: Data was retrospectively collected from the institutional trauma registry and electronic medical record, including all pediatric patients (age <18 y) who triggered a trauma team activation (1/2014 - 12/2021). Three ground-truths were used to label training data: 1) Cribari (Injury Severity Score >15 = full activation), 2) NFTI (positive for any of 6 criteria = full activation), and 3) the union of Cribari+NFTI (either positive = full activation). RESULTS: Of 1,366 patients triaged by trained staff, 143 (10.47%) were considered under-triaged using Cribari, 210 (15.37%) using NFTI, and 273 (19.99%) using Cribari+NFTI. NFTI and Cribari+NFTI were more sensitive to under-triage in patients with penetrating mechanisms of injury (p = 0.006), specifically stab wounds (p = 0.014), compared to Cribari, but Cribari indicated over-triage in more patients who required prehospital airway management (p < 0.001), CPR (p = 0.017), and who had mean lower GCS scores on presentation (p < 0.001). The mortality rate was higher in the Cribari over-triage group (7.14%, n = 9) compared to NFTI and Cribari+NFTI (0.00%, n = 0, p = 0.005). CONCLUSION: To prioritize patient safety, Cribari+NFTI appears best for training a machine learning algorithm to predict trauma team activation level.

Reconstruction of Full-Thickness Eyelid Defects Following Tumor Resection: The Bucket Handle Modification.

PURPOSE: To describe a modified approach for full-thickness lower eyelid defect reconstruction. METHODS: This is a retrospective review of 5 patients with large full-thickness lower eyelid defects after tumor resection requiring reconstruction. For these lower eyelid defects, a lateral-based or superior-based tarsoconjunctival pedicle flap from the upper eyelid was used to rebuild the posterior lamella. In all cases, the anterior lamella was supplied from an adjacent myocutaneous flap in a bucket handle configuration. Data collection included tumor type and location, size of eyelid defect, presence of canalicular involvement, postoperative eyelid position, patient satisfaction, and complication rates. RESULTS: Five eyelids of 5 patients underwent Mohs micrographic excision of basal cell carcinoma followed by reconstruction with a bucket handle flap. Age range was 68 to 96 years old (mean of 81 y). Five patients presented with lower eyelid involvement. The defect size ranged from 80% to 100% of the eyelid. Three patients had canalicular involvement and required bicanalicular nasolacrimal stent placement. After reconstruction, all patients showed good eyelid apposition to the globe with excellent esthetic outcome. No revision procedures were done. Average follow-up time was 13 months (range of 8 to 21 mo). CONCLUSION: The bucket handle flap for full-thickness eyelid reconstruction is a simple technique that allows for preservation of all anatomical layers of the anterior lamella. This technique shows promising functional and esthetic outcomes.

Exploring the Molecular Tumor Microenvironment and Translational Biomarkers in Brain Metastases of Non-Small-Cell Lung Cancer.

Brain metastases represent a significant clinical challenge in the treatment of non-small-cell lung cancer (NSCLC), often leading to a severe decline in patient prognosis and survival. Recent advances in imaging and systemic treatments have increased the detection rates of brain metastases, yet clinical outcomes remain dismal due to the complexity of the metastatic tumor microenvironment (TME) and the lack of specific biomarkers for early detection and targeted therapy. The intricate interplay between NSCLC tumor cells and the surrounding TME in brain metastases is pivotal, influencing tumor progression, immune evasion, and response to therapy. This underscores the necessity for a deeper understanding of the molecular underpinnings of brain metastases, tumor microenvironment, and the identification of actionable biomarkers that can inform multimodal treatment approaches. The goal of this review is to synthesize current insights into the TME and elucidate molecular mechanisms in NSCLC brain metastases. Furthermore, we will explore the promising horizon of emerging biomarkers, both tissue- and liquid-based, that hold the potential to radically transform the treatment strategies and the enhancement of patient outcomes.

Evaluating the Accuracy of ChatGPT and Google BARD in Fielding Oculoplastic Patient Queries: A Comparative Study on Artificial versus Human Intelligence.

PURPOSE: This study evaluates and compares the accuracy of responses from 2 artificial intelligence platforms to patients' oculoplastics-related questions. METHODS: Questions directed toward oculoplastic surgeons were collected, rephrased, and input independently into ChatGPT-3.5 and BARD chatbots, using the prompt: "As an oculoplastic surgeon, how can I respond to my patient's question?." Responses were independently evaluated by 4 experienced oculoplastic specialists as comprehensive, correct but inadequate, mixed correct and incorrect/outdated data, and completely incorrect. Additionally, the empathy level, length, and automated readability index of the responses were assessed. RESULTS: A total of 112 patient questions underwent evaluation. The rates of comprehensive, correct but inadequate, mixed, and completely incorrect answers for ChatGPT were 71.4%, 12.9%, 10.5%, and 5.1%, respectively, compared with 53.1%, 18.3%, 18.1%, and 10.5%, respectively, for BARD. ChatGPT showed more empathy (48.9%) than BARD (13.2%). All graders found that ChatGPT outperformed BARD in question categories of postoperative healing, medical eye conditions, and medications. Categorizing questions by anatomy, ChatGPT excelled in answering lacrimal questions (83.8%), while BARD performed best in the eyelid group (60.4%). ChatGPT's answers were longer and potentially more challenging to comprehend than BARD's. CONCLUSION: This study emphasizes the promising role of artificial intelligence-powered chatbots in oculoplastic patient education and support. With continued development, these chatbots may potentially assist physicians and offer patients accurate information, ultimately contributing to improved patient care while alleviating surgeon burnout. However, it is crucial to highlight that artificial intelligence may be good at answering questions, but physician oversight remains essential to ensure the highest standard of care and address complex medical cases.

A Real-World Precision Medicine Program Including the KidneyIntelX Test Effectively Changes Management Decisions and Outcomes for Patients With Early-Stage Diabetic Kidney Disease.

INTRODUCTION/OBJECTIVE: The KidneyIntelX is a multiplex, bioprognostic, immunoassay consisting of 3 plasma biomarkers and clinical variables that uses machine learning to predict a patient's risk for a progressive decline in kidney function over 5 years. We report the 1-year pre- and post-test clinical impact on care management, eGFR slope, and A1C along with engagement of population health clinical pharmacists and patient coordinators to promote a program of sustainable kidney, metabolic, and cardiac health. METHODS: The KidneyIntelX in vitro prognostic test was previously validated for patients with type 2 diabetes and diabetic kidney disease (DKD) to predict kidney function decline within 5 years was introduced into the RWE study (NCT04802395) across the Health System as part of a population health chronic disease management program from [November 2020 to April 2023]. Pre- and post-test patients with a minimum of 12 months of follow-up post KidneyIntelX were assessed across all aspects of the program. RESULTS: A total of 5348 patients with DKD had a KidneyIntelX assay. The median age was 68 years old, 52% were female, 27% self-identified as Black, and 89% had hypertension. The median baseline eGFR was 62 ml/min/1.73 m2, urine albumin-creatinine ratio was 54 mg/g, and A1C was 7.3%. The KidneyIntelX risk level was low in 49%, intermediate in 40%, and high in 11% of cases. New prescriptions for SGLT2i, GLP-1 RA, or referral to a specialist were noted in 19%, 33%, and 43% among low-, intermediate-, and high-risk patients, respectively. The median A1C decreased from 8.2% pre-test to 7.5% post-test in the high-risk group (P < .001). UACR levels in the intermediate-risk patients with albuminuria were reduced by 20%, and in a subgroup treated with new scripts for SGLT2i, UACR levels were lowered by approximately 50%. The median eGFR slope improved from -7.08 ml/min/1.73 m2/year to -4.27 ml/min/1.73 m2/year in high-risk patients (P = .0003), -2.65 to -1.04 in intermediate risk, and -3.26 ml/min/1.73 m2/year to +0.45 ml/min/1.73 m2/year in patients with low-risk (P < .001). CONCLUSIONS: Deployment and risk stratification by KidneyIntelX was associated with an escalation in action taken to optimize cardio-kidney-metabolic health including medications and specialist referrals. Glycemic control and kidney function trajectories improved post-KidneyIntelX testing, with the greatest improvements observed in those scored as high-risk.

Clinical outcomes and frequency of persistent infection among immunosuppressed patients treated with bebtelovimab for COVID-19 infection at an ambulatory cancer center.

BACKGROUND: There are limited data on clinical outcomes associated with the use of bebtelovimab for the treatment of coronavirus disease 2019 (COVID-19) among cancer patients. We aimed to define the clinical characteristics and outcomes among patients receiving bebtelovimab as part of the COVID-19 therapeutics program at our cancer center. METHODS: This is a retrospective cohort study of immunosuppressed adult patients who received bebtelovimab at Fred Hutchinson Cancer Center between March 2022, and November 2022. We reviewed medical records to capture the date of the first positive COVID-19 test, clinical characteristics, outcomes, and follow-up COVID-19 testing for 60 days after the first positive. Persistent infection was defined as a positive test beyond day 30; these patients were reviewed beyond day 60. RESULTS: Among 93 patients who received bebtelovimab, 64 (69%) had hematologic malignancy. Sixty-nine (74%) patients received bebtelovimab within 2 days after diagnosis. Two (2%) patients were hospitalized, none required ICU care, and one patient died on day 52; although it is unknown if death was directly related to COVID-19. Ten (11%) patients had persistent COVID-19 infection; of these, four received additional COVID-19 therapy with either nirmatrelvir/ritonavir or remdesivir, and five out of six patients with sequencing data available had spike protein mutations associated with bebtelovimab resistance. CONCLUSION: A coordinated systems-based approach led to prompt initiation of bebtelovimab within two days of testing positive in most patients. We observed few hospitalizations or deaths. Persistent infection was noted in 11% of patients with four requiring additional therapies, highlighting a need for novel strategies to manage immunosuppressed patients.

The influence of orbital architecture on strabismus in craniosynostosis.

PURPOSE: To better characterize the correlation of bony orbital dysmorphology with strabismus in craniosynostosis. METHODS: The medical records of patients with craniosynostosis with and without strabismus seen at Rady Children's Hospital (San Diego, CA) from March 2020 to January 2022 were reviewed retrospectively in this masked, case-control study. Computed tomography scans of the orbits were analyzed to obtain dimensions of the orbital entrance and orbital cone. Primary outcome was correlation of strabismus with orbital measurements. RESULTS: A total of 30 orbits from 15 patients with strabismus and 15 controls were included. Craniofacial disorders included in the study were nonsyndromic craniosynostosis (63%), Crouzon syndrome (13%), Apert syndrome (13%), and Pfeiffer syndrome (10%). Orbital index (height:width ratio) (P = 0.01) and medial orbital wall angle (P = 0.04) were found to differ significantly between the strabismus and control groups. CONCLUSIONS: In our small cohort, bony orbital dimensions, including the ratio of orbital height to width and bowing of the medial orbital wall, were associated with strabismus in craniosynostosis.

Transcutaneous retrobulbar amphotericin B for rhino-orbital-cerebral mucormycosis: a multi-center retrospective comparative study.

PURPOSE: To assess whether transcutaneous retrobulbar amphotericin B injections (TRAMB) reduce exenteration rate without increasing mortality in rhino-orbital-cerebral mucormycosis (ROCM). METHODS: In this retrospective case-control study, 46 patients (51 eyes) with biopsy-proven ROCM were evaluated at 9 tertiary care institutions from 1998 to 2021. Patients were stratified by radiographic evidence of local orbital versus extensive involvement at presentation. Extensive involvement was defined by MRI or CT evidence of abnormal or loss of contrast enhancement of the orbital apex with or without cavernous sinus, bilateral orbital, or intracranial extension. Cases (+TRAMB) received TRAMB as adjunctive therapy while controls (-TRAMB) did not. Patient survival, globe survival, and vision/motility loss were compared between +TRAMB and -TRAMB groups. A generalized linear mixed effects model including demographic and clinical covariates was used to evaluate the impact of TRAMB on orbital exenteration and disease-specific mortality. RESULTS: Among eyes with local orbital involvement, exenteration was significantly lower in the +TRAMB group (1/8) versus -TRAMB (8/14) (p = 0.04). No significant difference in mortality was observed between the ±TRAMB groups. Among eyes with extensive involvement, there was no significant difference in exenteration or mortality rates between the ±TRAMB groups. Across all eyes, the number of TRAMB injections correlated with a statistically significant decreased rate of exenteration (p = 0.048); there was no correlation with mortality. CONCLUSIONS: Patients with ROCM with local orbital involvement treated with adjunctive TRAMB demonstrated a lower exenteration rate and no increased risk of mortality. For extensive involvement, adjunctive TRAMB does not improve or worsen these outcomes.

Analysis of health care facility-onset Clostridioides difficile infection (CDI) in a hematopoietic cell transplant (HCT) unit: A call for diagnostic stewardship in a complex patient population.

Nearly half the patients identified as having health care facility-onset Clostridioides difficile infections on a hematopoietic cell transplant unit had an alternative clinical explanation for diarrhea, including conditioning regimen toxicity or other medications. Our study supports that targeted diagnostic stewardship interventions should be explored and that additional risk-adjustments considered for facilities with oncology hematopoietic cell transplant wards in the National Healthcare Safety Network LabID Clostridioides difficile infection standardized infection ratio model.

A comparison of proptosis reduction with teprotumumab versus surgical decompression based on fat-to-muscle ratio in thyroid eye disease.

PURPOSE: To explore if orbital fat-to-muscle ratio (FMR) is predictive of whether surgical decompression or teprotumumab leads to greater proptosis reduction in thyroid eye disease (TED). METHODS: A single-center retrospective cohort study comparing surgical decompression with teprotumumab according to FMR. All TED patients completing an 8-dose course of teprotumumab between January 2020 and September 2022 and all patients undergoing bony orbital decompression from January 2017 to December 2019 were included. Subjects were excluded if they were <18 years, received both surgical decompression and teprotumumab, or lacked orbital imaging. The primary exposure variable was teprotumumab or surgical decompression. The secondary exposure variable was baseline FMR. The primary outcome measure was change in proptosis (mm). RESULTS: Thirty-eight patients, mean age 53.5 years (±11.4), were included in the teprotumumab group and 160 patients, mean age 48 years (±11.1), in the surgical group. Average proptosis reduction after teprotumumab and surgical decompression was 3 mm (±1.44) and 5 mm (±1.75), respectively. The FMR was stratified at the median of 1.80. In subjects with FMR < 1.80, teprotumumab showed equivalent proptosis reduction compared to surgical decompression, -0.33 mm (SE 1.32) p = .802. In subjects with FMR ≥ 1.80, surgical decompression led to significantly more proptosis reduction than teprotumumab, 3.01 mm (SE 0.54), p < .001. CONCLUSIONS: Baseline FMR can be used to counsel patients as to proptosis reduction with teprotumumab versus surgery. Subjects with low FMR obtain comparable proptosis reduction with teprotumumab or surgery, whereas high FMR is associated with more significant proptosis reduction following surgery over teprotumumab.

Machine Learning Improves the Accuracy of Trauma Team Activation Level Assignments in Pediatric Patients.

BACKGROUND: The assignment of trauma team activation levels can be conceptualized as a classification task. Machine learning models can be used to optimize classification predictions. Our purpose was to demonstrate proof-of-concept for a machine learning tool for predicting trauma team activation levels in pediatric patients with traumatic injuries. METHODS: Following IRB approval, we retrospectively collected data from the institutional trauma registry and electronic medical record at our Pediatric Trauma Center for all patients (age <18 y) who triggered a trauma team activation (1/2014-12/2021), including: demographics, mechanisms of injury, comorbidities, pre-hospital interventions, numeric variables, and the six "Need for Trauma Intervention (NFTI)" criteria. Three machine learning models (Logistic Regression, Random Forest, Support Vector Machine) were tested 1000 times in separate trials using the union of the Cribari and NFTI metrics as ground-truth (Injury Severity Score >15 or positive for any of 6 NFTI criteria = full activation). Model performance was quantified and compared to emergency department (ED) staff. RESULTS: ED staff had 75% accuracy, an area under the curve (AUC) of 0.73 ± 0.04, and an F1 score of 0.49. The best performing of all machine learning models, the support vector machine, had 80% accuracy, AUC 0.81 ± 4.1e-5, F1 Score 0.80, with less variance compared to other models and ED staff. CONCLUSIONS: All machine learning models outperformed ED staff in all performance metrics. These results suggest that data-driven methods can optimize trauma team activations in the ED, with potential improvements in both patient safety and hospital resource utilization. TYPE OF STUDY: Economic/Decision Analysis or Modeling Studies. LEVEL OF EVIDENCE: II.

Phosphorylation of RPT6 Controls Its Ability to Bind DNA and Regulate Gene Expression in the Hippocampus of Male Rats during Memory Formation.

Memory formation requires coordinated control of gene expression, protein synthesis, and ubiquitin-proteasome system (UPS)-mediated protein degradation. The catalytic component of the UPS, the 26S proteasome, contains a 20S catalytic core surrounded by two 19S regulatory caps, and phosphorylation of the 19S cap regulatory subunit RPT6 at serine 120 (pRPT6-S120) has been widely implicated in controlling activity-dependent increases in proteasome activity. Recently, RPT6 was also shown to act outside the proteasome where it has a transcription factor-like role in the hippocampus during memory formation. However, little is known about the proteasome-independent function of "free" RPT6 in the brain or during memory formation and whether phosphorylation of S120 is required for this transcriptional control function. Here, we used RNA-sequencing along with novel genetic approaches and biochemical, molecular, and behavioral assays to test the hypothesis that pRPT6-S120 functions independently of the proteasome to bind DNA and regulate gene expression during memory formation. RNA-sequencing following siRNA-mediated knockdown of free RPT6 revealed 46 gene targets in the dorsal hippocampus of male rats following fear conditioning, where RPT6 was involved in transcriptional activation and repression. Through CRISPR-dCas9-mediated artificial placement of RPT6 at a target gene, we found that RPT6 DNA binding alone may be important for altering gene expression following learning. Further, CRISPR-dCas13-mediated conversion of S120 to glycine on RPT6 revealed that phosphorylation at S120 is necessary for RPT6 to bind DNA and properly regulate transcription during memory formation. Together, we reveal a novel function for phosphorylation of RPT6 in controlling gene transcription during memory formation.

Effectiveness of treatment for iris melanoma: surgical versus radiotherapeutic approaches.

OBJECTIVE: To evaluate the effectiveness of preventing metastasis for each major treatment modality for iris melanoma. DESIGN: Retrospective case series. PARTICIPANTS: Three hundred consecutive eyes with iris melanoma at a single tertiary referral centre for ocular oncology. METHODS: Retrospective analysis of eyes with iris melanoma, both with (n = 69 eyes) and without (n = 231 eyes) ciliary body extension, was undertaken for metastasis-free survival at 5, 10, and 20 years based on type of treatment, including globe-sparing surgical resection (n = 169 eyes), plaque radiotherapy (n = 74 eyes), or enucleation (n = 57 eyes). RESULTS: For the total population, 5-, 10-, and 20-year metastasis-free survival rates were 95%, 93%, and 87%, respectively, and there was no difference in metastatic rates for tumours with versus without ciliary body extension (p = 0.95). Noninferiority was demonstrated for surgical resection and plaque radiotherapy, with metastasis-free survival rates of 98%, 97%, and 94% for surgical resection and 94%, 94%, and 89% for plaque radiotherapy (p = 0.002). The rates for globe salvage were 94%, 92%, and 90% for surgical resection and 94%, 86%, and 86% for plaque radiotherapy (p = 0.003). However, metastasis-free survival was worse in patients who underwent enucleation (86%, 67%, and NA; p < 0.001). CONCLUSIONS: Metastasis-free survival and globe salvage following plaque radiotherapy and surgical resection are not inferior to either, but eyes undergoing enucleation demonstrated a lower metastasis-free survival, likely because enucleation is performed for larger, more extensive melanomas, often with secondary glaucoma. In this analysis, iris melanoma with ciliary body involvement did not increase the risk of metastasis.