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1.
Plast Reconstr Surg ; 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38722563

RESUMEN

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.

2.
Artículo en Inglés | MEDLINE | ID: mdl-38722772

RESUMEN

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.

3.
Artículo en Inglés | MEDLINE | ID: mdl-38534072

RESUMEN

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.

4.
J Craniofac Surg ; 35(4): e325-e329, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38385685

RESUMEN

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.


Asunto(s)
Carcinoma Basocelular , Neoplasias de los Párpados , Cirugía de Mohs , Colgajos Quirúrgicos , Humanos , Anciano , Neoplasias de los Párpados/cirugía , Anciano de 80 o más Años , Estudios Retrospectivos , Masculino , Femenino , Carcinoma Basocelular/cirugía , Resultado del Tratamiento , Procedimientos de Cirugía Plástica/métodos , Blefaroplastia/métodos , Párpados/cirugía , Satisfacción del Paciente
5.
Kidney Blood Press Res ; 49(1): 173-183, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38350434

RESUMEN

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.


Asunto(s)
Hipertensión , Riñón , Animales , Ratones , Riñón/fisiopatología , Hipertensión/fisiopatología , Hipertensión/etiología , Hemodinámica , Presión Sanguínea/fisiología , Estado de Conciencia , Modelos Animales de Enfermedad , Masculino
6.
J AAPOS ; 28(1): 103812, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38219920

RESUMEN

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.


Asunto(s)
Acrocefalosindactilia , Craneosinostosis , Estrabismo , Niño , Humanos , Estudios de Casos y Controles , Estudios Retrospectivos , Craneosinostosis/complicaciones , Craneosinostosis/diagnóstico por imagen , Acrocefalosindactilia/complicaciones , Estrabismo/etiología , Estrabismo/complicaciones , Órbita/diagnóstico por imagen
7.
Ophthalmic Plast Reconstr Surg ; 40(3): 303-311, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38215452

RESUMEN

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.


Asunto(s)
Inteligencia Artificial , Humanos , Procedimientos Quirúrgicos Oftalmológicos/métodos , Encuestas y Cuestionarios
8.
Orbit ; 43(1): 41-48, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36880205

RESUMEN

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.


Asunto(s)
Oftalmopatías , Mucormicosis , Enfermedades Orbitales , Humanos , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Mucormicosis/diagnóstico por imagen , Mucormicosis/tratamiento farmacológico , Estudios Retrospectivos , Estudios de Casos y Controles , Enfermedades Orbitales/diagnóstico por imagen , Enfermedades Orbitales/tratamiento farmacológico , Oftalmopatías/tratamiento farmacológico
9.
Orbit ; 43(2): 222-230, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37978819

RESUMEN

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.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Exoftalmia , Oftalmopatía de Graves , Humanos , Persona de Mediana Edad , Oftalmopatía de Graves/tratamiento farmacológico , Oftalmopatía de Graves/cirugía , Estudios Retrospectivos , Exoftalmia/cirugía , Órbita/diagnóstico por imagen , Órbita/cirugía , Músculos Oculomotores/cirugía , Descompresión Quirúrgica/métodos
10.
J Clin Endocrinol Metab ; 109(1): 25-35, 2023 Dec 21.
Artículo en Inglés | MEDLINE | ID: mdl-37925673

RESUMEN

CONTEXT: Early inflammatory thyroid eye disease (TED) can lead to symptomatic chronic disease, including disabling proptosis. Teprotumumab, an insulin-like growth factor-1 receptor (IGF-1R) inhibitor, previously demonstrated efficacy in acute, high-inflammation TED trials. OBJECTIVE: We present data from the first placebo-controlled trial with teprotumumab in chronic/low disease activity TED. METHODS: This randomized double-masked, placebo-controlled trial, conducted at 11 US centers, enrolled adult participants with TED duration of 2 to 10 years, Clinical Activity Score (CAS) ≤ 1 or no additional inflammation or progression in proptosis/diplopia for ≥1 year, proptosis ≥3 mm from before TED and/or from normal, euthyroid/mildly hypo/hyperthyroid, no prior teprotumumab, and no steroids within 3 weeks of baseline. Patients received (2:1) intravenous teprotumumab or placebo once every 3 weeks (total 8 infusions). The primary endpoint was proptosis (mm) improvement at Week 24. Adverse events (AEs) were assessed. RESULTS: A total of 62 (42 teprotumumab and 20 placebo) patients were randomized. At Week 24, least squares mean (SE) proptosis improvement was greater with teprotumumab (-2.41 [0.228]) than with placebo (-0.92 [0.323]), difference -1.48 (95% CI -2.28, -0.69; P = .0004). Proportions of patients with AEs were similar between groups. Hyperglycemia was reported in 6 (15%) vs 2 (10%) and hearing impairment in 9 (22%) vs 2 (10%) with teprotumumab and placebo, respectively. AEs led to discontinuation in 1 teprotumumab (left ear conductive hearing loss with congenital anomaly) and 1 placebo patient (infusion-related). There were no deaths. CONCLUSION: Teprotumumab significantly improved proptosis vs placebo in longstanding/low inflammation TED, demonstrating efficacy regardless of disease duration/activity. The safety profile was comparable to that previously reported.


Asunto(s)
Exoftalmia , Oftalmopatía de Graves , Adulto , Humanos , Anticuerpos Monoclonales Humanizados/efectos adversos , Oftalmopatía de Graves/tratamiento farmacológico , Inflamación , Inhibidores de Proteínas Quinasas , Método Doble Ciego
11.
Ophthalmic Plast Reconstr Surg ; 39(6): e208-e210, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37656913

RESUMEN

The authors report 4 cases of cutaneous hypersensitivity reactions developing in the course of teprotumumab treatment for thyroid eye disease. The onset of the cutaneous hypersensitivity reaction was also observed during the treatment course in all cases, between the second and fifth infusions. Teprotumumab-related cutaneous reactions suggest a possible immunogenic component of the monoclonal antibody and highlight the importance of close monitoring during treatment.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Oftalmopatía de Graves , Humanos , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales
12.
J Neural Transm (Vienna) ; 130(10): 1269-1279, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37466750

RESUMEN

To compare the inter-rater reliability (IRR) of five clinical rating scales for video-based assessment of hemifacial spasm (HFS) motor severity. We evaluated the video recordings of 45 HFS participants recruited through the Dystonia Coalition. In Round 1, six clinicians with expertise in HFS assessed the participants' motor severity with five scales used to measure motor severity of HFS: the Jankovic rating scale (JRS), Hemifacial Spasm Grading Scale (HSGS), Samsung Medical Center (SMC) grading system for severity of HFS spasms (Lee's scale), clinical grading of spasm intensity (Chen's scale), and a modified version of the Abnormal Involuntary Movement Scale (Tunc's scale). In Round 2, clinicians rated the same cohort with simplified scale wording after consensus training. For each round, we evaluated the IRR using the intraclass correlation coefficient [ICC (2,1) single-rater, absolute-agreement, 2-way random model]. The scales exhibited IRR that ranged from "poor" to "moderate"; the mean ICCs were 0.41, 0.43, 0.47, 0.43, and 0.65 for the JRS, HSGS, Lee's, Chen's, and Tunc's scales, respectively, for Round 1. In Round 2, the corresponding IRRs increased to 0.63, 0.60, 0.59, 0.53, and 0.71. In both rounds, Tunc's scale exhibited the highest IRR. For clinical assessments of HFS motor severity based on video observations, we recommend using Tunc's scale because of its comparative reliability and because clinicians interpret the scale easily without modifications or the need for consensus training.


Asunto(s)
Distonía , Espasmo Hemifacial , Humanos , Espasmo Hemifacial/diagnóstico , Reproducibilidad de los Resultados
15.
JAMA Ophthalmol ; 141(4): 394-395, 2023 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-36862419

RESUMEN

A 72-year-old man had right-eye conjunctival injection, chemosis, eyelid edema, and pain with eye movements. Examination showed visual acuity of 20/50, reduced ocular motility in all gazes, proptosis, and chemosis. Treatment with vancomycin and ceftriaxone and ampicillin-sulbactam was followed by symptom worsening. What would you do next?


Asunto(s)
Exoftalmia , Mieloma Múltiple , Enfermedades Orbitales , Humanos , Mieloma Múltiple/complicaciones , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Enfermedades Orbitales/diagnóstico por imagen , Enfermedades Orbitales/tratamiento farmacológico , Inflamación
16.
Can J Ophthalmol ; 2023 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-37001560

RESUMEN

OBJECTIVE: To determine the cost-effectiveness of endoscopic dacryocystorhinostomy (DCR). METHODS: We constructed a Markov model in which patients with nasolacrimal duct obstruction received endoscopic DCR or no surgery. Incremental cost-effectiveness ratios, 1-way sensitivity analyses, and probabilistic sensitivity analyses were used to evaluate for model sensitivity to multiple model inputs. RESULTS: Endoscopic DCR was found to be cost-effective with an incremental cost-effectiveness ratio of US$2162 per quality-adjusted life-year. The model was most sensitive to the health utility deduction from epiphora. Probabilistic sensitivity analysis found endoscopic DCR to be cost-effective over no surgery 93.7% of the time. CONCLUSIONS: Endoscopic DCR is a cost-effective treatment for patients with epiphora. The model is very sensitive to the negative effect epiphora has on quality of life. With the advancement of health care technology and surgical techniques, the success rates of endoscopic DCR continue to improve and to be an even more efficacious and economical treatment for nasolacrimal duct obstruction.

17.
MAbs ; 15(1): 2189974, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36991534

RESUMEN

Bispecific antibodies continue to represent a growth area for antibody therapeutics, with roughly a third of molecules in clinical development being T-cell engagers that use an anti-CD3 binding arm. CD3 antibodies possessing cross-reactivity with cynomolgus monkey typically recognize a highly electronegative linear epitope at the extreme N-terminus of CD3 epsilon (CD3ε). Such antibodies have high isoelectric points and display problematic polyreactivity (correlated with poor pharmacokinetics for monospecific antibodies). Using insights from the crystal structure of anti-Hu/Cy CD3 antibody ADI-26906 in complex with CD3ε and antibody engineering using a yeast-based platform, we have derived high-affinity CD3 antibody variants with very low polyreactivity and significantly improved biophysical developability. Comparison of these variants with CD3 antibodies in the clinic (as part of bi- or multi-specifics) shows that affinity for CD3 is correlated with polyreactivity. Our engineered CD3 antibodies break this correlation, forming a broad affinity range with no to low polyreactivity. Such antibodies will enable bispecifics with improved pharmacokinetic and safety profiles and suggest engineering solutions that will benefit the large and growing sector of T-cell engagers.


Asunto(s)
Anticuerpos Biespecíficos , Animales , Macaca fascicularis , Linfocitos T , Complejo CD3 , Muromonab-CD3
18.
Ophthalmic Plast Reconstr Surg ; 39(3): 281-287, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36727790

RESUMEN

PURPOSE: To evaluate the prevalence of depression and anxiety among individuals with thyroid eye disease (TED) and identify sociodemographic risk factors using the NIH All of Us database. METHODS: Three hundred ninety eight cases with TED were compared with 1,592 controls with demographics matching the 2020 US Census. Primary outcomes were diagnosed depression or anxiety; Patient Health Questionnaire-9 (PHQ-9) scores and General Anxiety Disorder-7 (GAD-7) scores were included as secondary outcomes. We performed multivariable logistic regression to generate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between TED and depression and anxiety. RESULTS: Patients with TED were more likely to have depression (OR 2.72, 95% CI 2.08-3.56, p < 0.001) and anxiety (OR 2.82, 95% CI 2.16-3.70, p < 0.001) than controls. In patients with TED, female gender was an independent risk factor for both depression (OR 1.72; 95% CI 1.00-5.07, p = 0.05) and anxiety (OR 2.17, 95% CI 1.25-3.85, p = 0.006). Unemployment (OR 1.72, 95% CI 1.03-2.94, p = 0.04) and lower income (OR 0.88 for income as a continuous variable, 95% CI 0.79-0.99, p = 0.03) were risk factors for anxiety. Risk factors for more severe depression as assessed by PHQ-9 included lower income (OR 0.70, 95% CI 0.57-0.85, p < 0.001), and protective factors included Black race (OR 0.12, 95% CI 0.02-0.45, p = 0.002). Lower income was associated with more severe anxiety as assessed by GAD-7 (OR 0.77, 95% CI 0.64-0.94, p = 0.009). CONCLUSIONS: Patients with TED were more likely to develop depression and anxiety compared with controls. This study highlights the psychosocial impact of TED and associated socioeconomic risk factors.


Asunto(s)
Oftalmopatía de Graves , Salud Poblacional , Humanos , Femenino , Depresión/diagnóstico , Depresión/epidemiología , Depresión/psicología , Ansiedad/diagnóstico , Ansiedad/epidemiología , Ansiedad/psicología , Factores de Riesgo
19.
Ophthalmic Plast Reconstr Surg ; 39(2): e40-e43, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36700847

RESUMEN

The authors present the case of a middle-aged woman with subacute progressive swelling of the OD associated with pain and severely limited duction in all gazes. MRI demonstrated a ~3 cm circumscribed mass in the extraconal space, which displaced and distorted the globe and impinged upon ocular adnexa. She underwent lateral orbitotomy with bone osteotomy to remove the mass, and subsequent histopathologic examination showed woven bone set within a fibrotic background, microscopic features of fibrous dysplasia. Fibrous dysplasia is characterized by abnormal scar-like bony proliferation, typically within a preexisting structure of the skeletal system. To the authors' knowledge, this represents the first example of fibrous dysplasia presenting as an orbital mass unconnected to the craniofacial skeleton.


Asunto(s)
Displasia Fibrosa Ósea , Enfermedades Orbitales , Persona de Mediana Edad , Femenino , Humanos , Enfermedades Orbitales/cirugía , Órbita/cirugía , Osteotomía , Imagen por Resonancia Magnética
20.
Orbit ; 42(4): 455-458, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35576315

RESUMEN

Skin rejuvenation procedures have increasingly flooded the aesthetic market, one of which includes microneedling. In microneedling, multiple fine punctures of the skin are performed with a needle to induce neocollagenesis. Microneedling has increasingly been used to treat inflammatory acne, acne scarring, photodamaged skin, and even radiation dermatitis. We present a patient with a stable history of liquid injectable silicone (LIS) given 20 years prior who developed chronic periocular and facial hypersensitivity after undergoing microneedling at a medi-spa. Long-term steroids and immunosuppressants were needed for control. The patient's severe reaction and resistance to treatment highlights the potential complications of microneedling administered by a non-medical professional in the setting of prior injectable silicone.


Asunto(s)
Acné Vulgar , Técnicas Cosméticas , Hipersensibilidad Tardía , Humanos , Técnicas Cosméticas/efectos adversos , Siliconas/efectos adversos , Cicatriz/etiología , Acné Vulgar/terapia , Acné Vulgar/complicaciones , Hipersensibilidad Tardía/complicaciones , Resultado del Tratamiento
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