Sex-Based Analysis of Workflow and Outcomes in Acute Ischemic Stroke Patients Treated With Alteplase Versus Tenecteplase.

BACKGROUND: Understanding sex differences in stroke care is important in reducing potential disparities. Our objective was to explore sex differences in workflow efficiency, treatment efficacy, and safety in the AcT trial (Alteplase Compared to Tenecteplase). METHODS: AcT was a multicenter, registry-linked randomized noninferiority trial comparing tenecteplase (0.25 mg/kg) with alteplase (0.9 mg/kg) in acute ischemic stroke within 4.5 hours of onset. In this post hoc analysis, baseline characteristics, workflow times, successful reperfusion (extended Thrombolysis in Cerebral Infarction score ≥2b), symptomatic intracerebral hemorrhage, 90-day functional independence (modified Rankin Scale score, 0-1), and 90-day mortality were compared by sex. Mixed-effects regression analysis was used adjusting for age, stroke severity, and occlusion site for outcomes. RESULTS: Of 1577 patients treated with intravenous thrombolysis (2019-2022), 755 (47.9%) were women. Women were older (median, 77 [68-86] years in women versus 70 [59-79] years in men) and had a higher proportion of severe strokes (National Institutes of Health Stroke Scale score >15; 32.4% versus 24.9%) and large vessel occlusions (28.7% versus 21.5%) compared with men. All workflow times were comparable between sexes. Women were less likely to achieve functional independence (31.7% versus 39.8%; unadjusted relative risk, 0.80 [95% CI, 0.70-0.91]) and had higher mortality (17.7% versus 13.3%; unadjusted relative risk, 1.33 [95% CI, 1.06-1.69]). Adjusted analysis showed no difference in outcomes between sexes. CONCLUSIONS: Differences in prognostic factors of age, stroke severity, and occlusion site largely accounted for higher functional dependence and mortality in women. No sex disparities were apparent in workflow quality indicators. Given the integration of the AcT trial into clinical practice, these results provide reassurance that no major sex biases are apparent in acute stroke management throughout participating Canadian centers. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03889249.

Risk Factors for Chalazion Diagnosis and Subsequent Surgical Excision.

PURPOSE: To identify factors associated with chalazion diagnosis and surgical excision. METHODS: Patients with an incident chalazion diagnosis from 2002 to 2019 were compared 1:5 with matched controls. Multivariable logistic regression was performed to identify variables associated with diagnosis and surgical excision. RESULTS: Chalazion patients (n = 134,959) and controls (678,160) were analyzed. Risk factors for diagnosis included female sex, non-white race, northeast location, conditions affecting periocular skin and tear film (blepharitis, meibomian gland dysfunction, rosacea, pterygium), non-ocular inflammatory conditions (gastritis, inflammatory bowel disease, sarcoidosis, seborrheic dermatitis, Graves' disease), and smoking (p < .001 for all comparisons). Thirteen percent of patients with chalazion underwent subsequent surgical excision. Diabetes and systemic sclerosis diagnoses decreased odds of diagnosis (p < .001). Male sex, rosacea diagnosis, Black and Hispanic race, antibiotic use, and doxycycline use increased odds of surgery (p < .001). CONCLUSION: Female sex, non-white race, conditions affecting periocular skin and the tear film, several non-ocular inflammatory conditions, and smoking were risk factors for chalazion diagnosis. Male sex, rosacea diagnosis, Black and Hispanic race, antibiotic use, and doxycycline use were risk factors for surgical intervention for chalazion. Our results prompt further study of these variables and their relationship to chalazion diagnosis to understand physiology and improve clinical outcomes. Furthermore, the results of this study suggest early recognition and treatment of concomitant rosacea may serve an important role in the management of chalazion and in the prevention of surgical intervention.

Teaching NeuroImage: Rapidly Changing Symptoms With Multistep Migration of Clot in the Posterior Circulation After Tenecteplase for Acute Ischemic Stroke.

A 70-year-old man presented with acute vertigo and ataxia. CT angiogram revealed left V3 segment vertebral artery occlusion (Figure 1, A and B). He received tenecteplase (0.25 mg/kg IV bolus) and was transferred to our comprehensive stroke center due to the risk of early neurologic deterioration from clot migration that would necessitate thrombectomy. Repeat CT angiogram revealed migration to V4 segment with posterior inferior cerebellar artery reopacification and improving symptoms (Figure 1, C and D). Two hours post-tenecteplase, he developed aphasia, right hemianopia, and sensorimotor symptoms (National Institutes of Health Stroke Scale 15). Angiogram showed a left P1 posterior cerebral artery thrombus. Attempted thrombectomy resulted in further migration to P2. MRI demonstrated multiple infarcts (Figure 2), representing stepwise ischemia from dynamic clot movement. Clot reformation from hypercoagulability or re-embolization seemed unlikely, given short time course and exclusive posterior circulation involvement.

Cryptophthalmos: associated syndromes and genetic disorders.

PURPOSE: Cryptophthalmos is a rare congenital condition caused by anomalous eyelid development where the eyelid folds do not develop or fail to separate. Cryptophthalmos can be unilateral or bilateral and can occur in isolation or as part of an underlying syndrome. We aim to identify genetic syndromes associated with cryptophthalmos to facilitate genetic diagnosis. METHODS: We performed a retrospective medical record review of all patients diagnosed with cryptophthalmos followed at a single center between 2000 and 2020. The analysis included medical history, clinical examination findings, and genetic testing results. RESULTS: Thirteen patients were included, 10 (77%) males, mean age of 2.4 years. Eight (61%) had bilateral cryptophthalmos, and 4 (31%) had complete cryptophthalmos. Associated ocular abnormalities included corneal opacities (13/13, 100%), upper eyelid colobomas (12/13, 92%), and microphthalmia/clinical anophthalmia (3/13, 23%). All cases of complete cryptophthalmos had bilateral disease. An underlying clinical or molecular diagnosis was identified in 10/13 (77%) cases, including Fraser syndrome (n = 5), amniotic band syndrome (n = 1), FREM1-related disease (n = 1), Goldenhar versus Schimmelpenning syndrome (n = 1), MOTA syndrome (n = 1), and CELSR2-related disease (n = 1). CONCLUSION: This is the first report of a possible association between cryptophthalmos and biallelic CELSR2 variants. Children with cryptophthalmos, especially those with extra-ocular involvement, should be referred for comprehensive genetic evaluation.

Recanalization and outcomes after cerebral venous thrombosis: a systematic review and meta-analysis.

Background: Recanalization in cerebral venous thrombosis (CVT) can begin as early as 1 week after initiating therapeutic anticoagulation. The clinical significance of recanalization remains uncertain. Objectives: We aimed to investigate the association between recanalization and functional outcomes and explored predictors of recanalization. Methods: A systematic literature search was conducted (EMBASE, MEDLINE, Cochrane library) to identify: (1) patients with CVT aged ≥18 years treated with anticoagulation only; (2) case series, cohort, or randomized controlled trial studies; and (3) reported recanalization rates and functional outcomes using either a modified Rankin Scale (mRS) or sequelae of CVT at last follow-up. Meta-analysis was performed using pooled odds ratios (ORs) with exploration of sex and age effects using meta-regression. Results: Twenty-three studies were eligible with 1418 individual patients in total. Timing of reimaging and clinical reassessment was variable. Absence of recanalization was associated with increased odds of an unfavorable functional outcome (mRS 2-6 versus 0-1; OR, 3.66; 95% CI, 1.73-7.74; p = 0.001), CVT recurrence (OR, 8.81; 95% CI, 1.63-47.7; p = 0.01), and chronic headache (OR, 2.78; 95% CI, 1.16-6.70; p = 0.02). On meta-regression, the relationship between recanalization and mRS differed by the proportion of female patients, where lower proportions of women were associated with higher likelihood of a worse outcome, but not by mean participant age. There was no incremental benefit of full compared with partial recanalization with respect to favorable mRS or recurrence, but odds of chronic headache were higher with partial versus full recanalization (OR, 3.80; 95% CI, 1.43-10.11; p = 0.008). Epilepsy and visual sequelae were not associated with recanalization. Conclusions: Absence of recanalization was associated with worse functional outcomes, CVT recurrence, and headache, but outcomes were modified by sex. The degree of recanalization was significant in relation to headache outcomes, where partial compared with complete recanalization resulted in a greater likelihood of residual headache. Prospective studies with common timing of repeat clinical-neuroimaging assessments will help to better ascertain the relationship and directionality between the degree of recanalization and outcomes.

Cavernous sinus thrombosis with bilateral orbital vein involvement and diffuse ischemic retinopathy / Trombose do seio cavernoso com envolvimento bilateral das veias orbitais e retinopatia isquêmica difusa

ABSTRACT A 53-year-old man with a 3-day history of periorbital swelling and vision loss in the left eye was found to have septic cavernous sinus thrombosis with bilateral orbital vein involvement causing congestive orbitopathy. He was treated with an emergent canthotomy and cantholysis, intraocular pressure-lowering drops, antibiotics, anticoagulation, and serial examinations. Optical coherence tomography ultimately revealed diffuse ischemic destruction of both layers of the retina, which suggested occlusion of the ophthalmic artery or the short posterior ciliary arteries and central retinal artery without intracavernous internal carotid artery involvement. The patient remained without light perception in the left eye after treatment.

RESUMO Um homem de 53 anos, com história de 3 dias de edema periorbital e perda de visão no olho esquerdo, apresentou trombose séptica do seio cavernoso com envolvimento bilateral das veias orbitais, causando uma orbitopatia congestiva. O paciente foi tratado com uma cantotomia e cantólise de emergência, colírios para redução da pressão intraocular, antibióticos, anticoagulantes e exames seriados. A tomografia de coerência óptica finalmente demonstrou destruição isquêmica difusa de ambas as camadas da retina, sugerindo uma oclusão da artéria oftálmica ou das artérias ciliares posteriores curtas e da artéria retiniana central, com ausência de envolvimento do segmento intracavernoso da artéria carótida interna. O paciente permaneceu sem percepção luminosa no olho esquerdo.

Sox17 mediates adult arterial endothelial cell adaptation to hemodynamics.

Sox17 is a critical regulator of arterial identity during early embryonic vascular development. However, its role in adult endothelial cells (ECs) are not fully understood. Sox17 is highly expressed in arterial ECs but not in venous ECs throughout embryonic development to adulthood suggesting that it may play a functional role in adult arteries. Here, we investigated Sox17 mediated phenotypical changes in adult ECs. To precisely control the temporal expression level of Sox17, we designed a tetracycline-inducible lentiviral gene expression system to express Sox17 selectively in cultured venous ECs. We confirmed that Sox17-induced ECs exhibit a gene profile favoring arterial and tip cell identity. Furthermore, in comparison to control ECs, Sox17-activated ECs under shear leads to greater expression of arterial markers and suppression of venous identity. These data suggest that Sox17 enables greater hemodynamic adaptability of ECs in response to fluid shear stress. Here, we also demonstrate key morphogenic behaviors of Sox17-mediated ECs. In both vasculogenic and angiogenic 3D fibrin gel studies, Sox17-mediated ECs prefer to form cohesive vessels with one another while interfering the vessel formation of the control ECs. Sox17-mediated ECs elicit hyper-sprouting behavior in the presence of pericytes but not fibroblasts, suggesting Sox17 mediated sprouting frequency is dependent on supporting cell type. Using a microfluidic chip, we also show that Sox17-mediated ECs maintain thinner diameter vessels that do not widen under interstitial flow like the control ECs. Taken together, these data showed that Sox17 mediated EC gene expression and phenotypical changes are highly modulated in the context of biomechanical stimuli, suggesting Sox17 plays a role in regulating the arterial ECs adaptability under arterial hemodynamics as well as tip cells behavior during angiogenesis and vasculogenesis. The results from this study may be valuable in improving vein graft adaptation to arterial hemodynamics and bioengineering microvasculature for tissue engineering applications.

Cavernous sinus thrombosis with bilateral orbital vein involvement and diffuse ischemic retinopathy.

A 53-year-old man with a 3-day history of periorbital swelling and vision loss in the left eye was found to have septic cavernous sinus thrombosis with bilateral orbital vein involvement causing congestive orbitopathy. He was treated with an emergent canthotomy and cantholysis, intraocular pressure-lowering drops, antibiotics, anticoagulation, and serial examinations. Optical coherence tomography ultimately revealed diffuse ischemic destruction of both layers of the retina, which suggested occlusion of the ophthalmic artery or the short posterior ciliary arteries and central retinal artery without intracavernous internal carotid artery involvement. The patient remained without light perception in the left eye after treatment.

Mohs Micrographic Surgery for Facial Merkel Cell Carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare malignant cutaneous tumor with frequent metastases. They often appear in the face where cosmetic and functional outcome is critical. Mohs micrographic surgery (MMS) is a controlled intervention that optimizes negative margins without sacrificing tissue. OBJECTIVE: A comprehensive assessment of outcomes of MMS-treated facial MCC will help guide clinicians in surgical and medical management. METHODS & MATERIALS: Retrospective review identified facial MCC cases treated with MMS at a single institution from January 2005 to August 2020. Tumor characteristics and outcomes were recorded and descriptive and predictive analyses were performed. RESULTS: 34 cases were reviewed with a mean followup of 34.4 months. The most common sites were the forehead, cheek-jaw region, and nasal ala. 2 (5.9%) patients had local recurrence by a mean of 4.3 months. No documented variables were significantly associated with local recurrence. 8 (23.5%) patients had progression to metastasis by a mean of 9.4 months. Younger age at biopsy and surgery, male sex, and intraoperative detection of in-transit disease were significantly associated with progression to metastasis. CONCLUSIONS: In summary, the tissue-sparing approach of MMS may be beneficial for MCC in cosmetically and functionally sensitive facial locations as it preserves tissue without compromising outcomes.

Sebaceous Carcinoma of the Face Treated With Mohs Micrographic Surgery.

BACKGROUND: Mohs micrographic surgery (MMS) for sebaceous carcinoma (SC) may reduce local recurrence rates, but published case series have small cohorts and limited follow-up. Mohs micrographic surgery is particularly suitable for sensitive functional and cosmetic locations, such as the face, because it facilitates tissue conservation using complete peripheral and deep margin assessment before reconstruction. Coordinated care between Mohs and oculoplastic surgeons has not been described. OBJECTIVE: To assess rates of local recurrence and metastasis after MMS of facial SC and to describe coordinated care between Mohs and oculoplastic surgeons. MATERIALS AND METHODS: Retrospective review identified facial SC cases treated with MMS at a single institution from January 2005 to August 2020. Tumor characteristics and outcomes were recorded. Descriptive and predictive analyses were performed. RESULTS: Forty-nine cases were reviewed with a mean follow-up of 51 months. The most common sites were periorbital, infraorbital cheek, and nasal ala. No patients experienced regional recurrence after MMS. One patient with Muir-Torre syndrome developed metastatic recurrence (at 82.9 months). All patients underwent 2-stage reconstruction with dermatology-performed MMS and oculoplastic reconstruction. CONCLUSION: Collaboration between Mohs and oculoplastic surgeons with a tissue-sparing approach of MMS can reduce recurrence and optimize cosmesis and function for central facial SC.

Changes in Intraocular Pressure with Use of Periocular Triamcinolone Cream.

Purpose: To evaluate the effect of periocular topical triamcinolone cream on intraocular pressure. Methods: A retrospective chart review identified 57 patients, 114 eyes using triamcinolone cream (0.1%, 0.025%) with subsequent intraocular pressure (IOP) checks at three follow-up visits. Descriptive, univariate, and multivariate analyses were performed to assess effects of age, therapy duration, consecutive weeks on steroid, prescription strength, time of day, and method of measurement on IOP levels. Generalized Estimating Equations were used in regression models to account for correlation of eyes within subjects and across visits. Results: We identified 57 patients using triamcinolone cream for allergic or eczematous dermatitis of the eyelid. Prescription strengths were 0.025% or 0.1% and patients were followed for a median of 4.9 months. Measurements of IOP at baseline did not change as compared to all IOP measurements at follow-ups and did not change with steroid strength. The mean change in IOP at all follow-up visits was 0.07 mm Hg (95% confidence interval [CI]: -0.36, 0.50). After adjustment for the method of tonometer and the patient's age, the mean change was 0.03 mm Hg (95% CI: -0.68, 0.73, P = 0.93). Prescription strength and consecutive weeks of therapy were not associated with IOP. Two patients experienced a significant elevation in IOP of > 10 mm Hg, one through the concomitant consequences of systemic corticosteroids usage and the other through prolonged topical application. Conclusion: In patients taking periocular triamcinolone cream, there was no clinically meaningful change in mean IOP between baseline and follow-up visits, and IOP measurements were not related to variances in prescription strength or duration of therapy.

Cataracts in setting of multisystem inflammation after COVID-19 vaccination.

Purpose: To describe a unique case of bilateral cataract formation in the setting of multisystem inflammation after the 1st dose of the BNT162b2 mRNA COVID-19 vaccination. Observations: A previously healthy 20-year-old male developed intumescent bilateral cataracts leading to visual decline from 20/20 to 20/300-20/400 in each eye, likely from systemic inflammation after vaccination. Conclusion and importance: This is the first reported case of cataract formation following a COVID-19 vaccine. While ocular adverse effects associated with COVID-19 vaccination are rare, it is important to raise awareness of these entities amongst medical providers as the COVID-19 pandemic continues and vaccinations become widespread.

Ongoing Dizziness Following Acute COVID-19 Infection: A Single Center Pediatric Case Series.

BACKGROUND: Dizziness is a common concern discussed at adolescent medical visits. In this series, we describe 9 pediatric patients with postacute sequelae of severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2) who presented with persistent, debilitating dizziness for weeks to months after their acute infection. METHODS: Among the 9 patients, median age was 14 years (range: 11 to 17), 6 were female, and 8 had not received any SARS-CoV-2 vaccines. Five patients met diagnostic criteria for postural orthostatic tachycardia syndrome (POTS) by active standing testing and benefited from a combination of nonpharmacologic therapy (NPT) and medication. RESULTS: NPT alone did not improve symptoms in any patients. Patients who did not meet conventional criteria for POTS, but continued to have symptoms despite NPT compliance, also demonstrated subjective improvement in dizziness when medications were initiated. The majority of patients experienced improvement in dizziness and quality of life, including returning to sports teams and a regular school schedule. CONCLUSIONS: A review of the postacute sequelae of SARS-CoV-2 literature demonstrates increasing recognition of a subset of patients who develop autonomic dysfunction, including POTS, although the etiology and prognosis are not completely understood. Our case series aims to highlight the phenomenon of dysautonomia after acute SARS-CoV-2 infection and its response to therapy.

Orbital and periorbital dermoid cysts: a retrospective analysis of 270 lesions.

PURPOSE: To report the clinical characteristics and intraoperative findings of periorbital and orbital dermoid cysts and their relationship to location and rupture. METHODS: Retrospective review of 270 cases with orbital or periorbital dermoid cysts that presented over a period of 11 years. Patients were included if diagnosis of dermoid cyst was made by histopathologic analysis. Clinical characteristics and operative outcomes were recorded and analyzed with Chi-squared analyses or univariate regression. Multivariate binary logistic regression was performed to assess predictors of location and rupture. RESULTS: Dermoids frequently occurred unilaterally and were more frequently described as mobile (61.5%), followed by fixed (30.8%), and partially fixed (7.7%). Dermoid rigidity was most commonly described as firm (75.5%), followed by cystic, soft, and rubbery. The most common dermoid location was superotemporal (60.4%). On Chi-squared analysis, superotemporal lesions were less likely to have orbital extension than non-superotemporal lesions (OR 0.28, 95% CI: 0.11-0.70, p = .01), less likely to undergo CT (OR 0.16, 95% CI: 0.06-0.41, p < .01) or MRI (OR 0.23, 95% CI: 0.13-0.41, p < .01), more likely to be described as mobile (OR 2.91, 95% CI: 1.32-6.43, p = .01), and less likely to rupture intraoperatively (OR 0.28, 95% CI: 0.11-0.73, p = .01). No variables were associated with rupture in multivariate analysis. CONCLUSION: Superotemporal dermoid cysts are common in the pediatric population, less likely to have orbital extension, undergo imaging, and have intraoperative rupture when compared to other locations in the orbit.

Extra kinetic dimensions for label discrimination.

Due to its sensitivity and versatility, fluorescence is widely used to detect specifically labeled biomolecules. However, fluorescence is currently limited by label discrimination, which suffers from the broad full width of the absorption/emission bands and the narrow lifetime distribution of the bright fluorophores. We overcome this limitation by introducing extra kinetic dimensions through illuminations of reversibly photoswitchable fluorophores (RSFs) at different light intensities. In this expanded space, each RSF is characterized by a chromatic aberration-free kinetic fingerprint of photochemical reactivity, which can be recovered with limited hardware, excellent photon budget, and minimal data processing. This fingerprint was used to identify and discriminate up to 20 among 22 spectrally similar reversibly photoswitchable fluorescent proteins (RSFPs) in less than 1s. This strategy opens promising perspectives for expanding the multiplexing capabilities of fluorescence imaging.

Updates in Cerebral Venous Thrombosis.

PURPOSE OF REVIEW: Cerebral venous thrombosis (CVT) is a rare cause of stroke that most commonly affects younger women. Here, we review new literature relevant to the management and prognosis of individuals with CVT and ongoing areas of uncertainty. RECENT FINDINGS: Direct-acting oral anticoagulants (DOACs) are being increasingly integrated into routine care but are not yet recommended by guidelines. Recent randomized clinical trials and available case series offer reassuring safety data. Routine use of endovascular therapy is not associated with improved outcomes. The relationship between recanalization and prognosis is uncertain. The evidence base for management of CVT continues to improve. Ongoing areas of uncertainty include duration of therapy and whether certain subgroups of patients may benefit from neurointervention or personalized approaches to antithrombotic strategy. The state of knowledge will continue to benefit from large collaborative international efforts, and integration of patient partnerships to identify research priorities.

Differentiating Human Pluripotent Stem Cells to Vascular Endothelial Cells for Regenerative Medicine, Tissue Engineering, and Disease Modeling.

Vasculature plays a vital role in human biology as blood vessels transport nutrients and oxygen throughout the body. Endothelial cells (ECs), specifically, are key as they maintain barrier functions between the circulating blood and the surrounding tissues. ECs derived from human pluripotent stem cells (hPSCs) are utilized to study vascular development and disease mechanisms within in vitro models. Additionally, ECs derived from induced pluripotent stem cells (iPSCs) hold great promise for advancing personalized medicine, cell therapies, and tissue-engineered constructs by creating patient-specific cell populations. Here, we describe a xeno-free, serum-free differentiation protocol for deriving ECs from hPSCs. In brief, mesoderm progenitor cells are derived via WNT pathway activation. Following this, EC maturation is achieved with exogenous vascular endothelial growth factor A (VEGFA) and basic fibroblast growth factor 2 (bFGF2). We have characterized these cells as expressing mature EC markers and have illustrated their functionality in vitro.