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BACKGROUND AND IMPORTANCE: Endovascular thrombectomy for patients with tandem occlusions could be challenging. Exposure to potential technical complications and bailout rescue techniques are of utmost importance. CLINICAL PRESENTATION: A 73-year-old woman with tandem internal carotid artery and middle cerebral artery lesions underwent an unsuccessful retrograde revascularization approach in the setting of tortuous anatomy. Antegrade approach revascularization was then pursued. Following cervical internal carotid artery revascularization, a triaxial system of aspiration catheter, microcatheter and micro guidewire was navigated through the stented curved cervical ICA and intracranial stent retriever pass was performed. Upon retrieving the clot-incorporated stent retriever with the intention to retrieve the entire stent retriever into the locally placed aspiration catheter, the triaxial system collapsed into the distal common carotid artery. Large thrombus was recovered from the aspiration catheter aspirate however the proximal end of stent retriever and distal internal carotid artery stent got tangled. After unsuccessful maneuvering to disentangle stent retriever from the internal carotid artery stent, we decided to attempt safe separation of the stent retriever from its pusher wire and leave behind the patent internal carotid artery stent/stent retriever metal construct in place. Gradual pulling pressure was applied to the stent retriever wire while maintaining distal exchange-length microwire access and fully inflated extracranial balloon over the entangled portion to ensure continuous vascular access. The stent retriever wire was then safely separated from the stent retriever and fully retracted outside the body. Delayed angiographic runs continued to demonstrate full patency of the internal carotid artery lumen. No residual dissection, spasm, or thrombus was noted. CONCLUSION: This case illustrates a novel bailout endovascular salvage technique that could be considered in such cases. These techniques minimize intraoperative complication, focus on patient safety, and promote efficiency for endovascular thrombectomy in unfavorable anatomy.
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Preliminary work suggested upregulation of inflammatory pathways in patients with common forms of ichthyosis. However, a comprehensive characterization of skin from various ichthyosis subtypes is unavailable, precluding the development of targeted treatments. Thus, we sought to characterize the immune and barrier profiles of common and subtype-specific skin transcriptomes in a large group of patients with ichthyosis. We performed a global RNA-sequencing analysis in 54 patients with ichthyosis (7 with Netherton syndrome, 13 with epidermolytic ichthyosis, 16 with lamellar ichthyosis, and 18 with congenital ichthyosiform erythroderma) and 40 healthy controls. Differentially expressed genes were defined on the basis of fold changes > 2 and false discovery rate < 0.05 criteria. We found robust and significant T helper (Th) 22/Th17 skewing in all subtypes (e.g., IL-17A/C/F, S100A7/8/9/12; P < 0.001) with modest changes in Th2 pathway, primarily in Netherton syndrome, and Th1 skewing in congenital ichthyosiform erythroderma. Across all subtypes (less evident in epidermolytic ichthyosis), lipid metabolism and barrier junction markers were downregulated (e.g., FA2H, CDH10/11/12/2; P < 0.05), whereas epidermal cornification and proliferation measures were upregulated (e.g., SPRR1A/1B/2C/2G, EREG; P < 0.05). Our findings suggest that the common ichthyosis variants share aberrations in Th17/Th22 and barrier function, with minimal Th2 modulation. This may help to elucidate the pathogeneses of these subtypes and inform the development of subtype-specific treatments.
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Hiperqueratosis Epidermolítica , Eritrodermia Ictiosiforme Congénita , Ictiosis Lamelar , Ictiosis , Síndrome de Netherton , Humanos , Hiperqueratosis Epidermolítica/genética , Ictiosis Lamelar/genética , TranscriptomaRESUMEN
PURPOSE: To report treatment of vitreous seeding of choroidal melanoma with monthly injections of intravitreal melphalan. METHODS: Case report. RESULTS: A 70-year-old white woman noted floaters in her left eye, and further examination revealed visual acuity of 20/30 in both eyes. Funduscopically, there was a mushroom-shaped choroidal melanoma in her left eye, measuring 9 mm in basal dimension and 4.8 mm in thickness. Notably, there was apical retinal invasion of melanoma with mild vitreous hemorrhage, without vitreous seeding. The tumor was treated with iodine-125 plaque radiotherapy using an apex dose of 70 Gy over 99 hours, designed to include the retinal invasion. The melanoma demonstrated complete regression into a nearly flat scar of 1 mm and remained stable over 4 years. Five years after radiotherapy, there were diffuse vitreous pigmented seeds of presumed melanoma origin, emanating from the site of retinal necrosis. This progressively worsened over the following 18 months, suspicious for viable melanoma cells, as visual acuity concurrently declined to 20/100. Treatment with intravitreal melphalan (10 µg/0.05 mL) was delivered on a monthly basis for 12 cycles, resulting in vitreous seeds regression, and preservation of the eye. Final visual acuity was 20/200. There were no treatment-related complications. CONCLUSION: Intravitreal melphalan can be considered in cases of vitreous seeding from uveal melanoma.
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Antineoplásicos Alquilantes/uso terapéutico , Neoplasias de la Coroides/tratamiento farmacológico , Melanoma/tratamiento farmacológico , Melfalán/uso terapéutico , Siembra Neoplásica , Neoplasias de la Retina/tratamiento farmacológico , Cuerpo Vítreo/efectos de los fármacos , Anciano , Neoplasias de la Coroides/diagnóstico por imagen , Neoplasias de la Coroides/patología , Femenino , Angiografía con Fluoresceína , Humanos , Inyecciones Intravítreas , Melanoma/diagnóstico por imagen , Melanoma/secundario , Neoplasias de la Retina/diagnóstico por imagen , Neoplasias de la Retina/secundario , Estudios Retrospectivos , Tomografía de Coherencia Óptica , Cuerpo Vítreo/patologíaRESUMEN
BACKGROUND: Traditional in-person discussion alone is often used for preoperative education in Mohs micrographic surgery (MMS). The appropriate use of more modern education techniques is not well defined in the MMS literature. OBJECTIVE: The authors aim to evaluate patient education techniques for MMS, address education in special populations, and highlight opportunities for improvement. METHODS AND MATERIALS: We performed a PubMed literature search with keywords "Mohs" and "education", "teaching", "understanding", "explanation", "preoperative", or "consent" with no restriction on publication time frame due to literature scarcity. RESULTS: Teledermatology consultation, MMS videos, 3D models, pamphlets/online materials, and shared medical appointments appear to be effective techniques (GRADE B). Analogies are also anecdotally helpful when integrated into traditional verbal education (GRADE C). The role of preoperative educational phone calls is more controversial (GRADE C). CONCLUSION: Regardless of the education technique utilized, no singular technique entirely replaces the traditional in-person discussion. Having access to multiple modalities can be beneficial for patients, allowing them options to choose their preferred method(s) of education. MMS is a difficult topic to conceptualize, and further research into educational techniques is needed to provide clear guidelines for Mohs surgeons.
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Dermatología/métodos , Cirugía de Mohs , Educación del Paciente como Asunto/métodos , Neoplasias Cutáneas/cirugía , Dermatología/instrumentación , Dermatología/organización & administración , Humanos , Modelos Anatómicos , Educación del Paciente como Asunto/organización & administración , Satisfacción del Paciente , Cuidados Preoperatorios/métodos , Mejoramiento de la Calidad , Consulta Remota/instrumentación , Consulta Remota/métodos , Consulta Remota/organización & administración , Grabación en VideoRESUMEN
Synthetic cannabinoids are a relatively new and increasingly popular recreational drug. While used for their hallucinogenic properties similar to natural cannabis, they have a greater and more serious side effect profile, including potentially severe neuropsychiatric toxicity. We report the cases of two patients with untreated schizophrenia who presented after ocular self-injury while intoxicated on K2. Both patients hallucinated that a bug was behind their eye, and in their attempts at removing the bug, damaged the periocular soft tissue. To our knowledge these are the first reports of ocular self-injury from synthetic cannabinoid intoxication.
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Cannabinoides , Lesiones Oculares , Conducta Autodestructiva , Cannabinoides/efectos adversos , Lesiones Oculares/inducido químicamente , Alucinaciones , Humanos , Conducta Autodestructiva/inducido químicamenteAsunto(s)
Antiinfecciosos , Coronavirus , Betacoronavirus , COVID-19 , Infecciones por Coronavirus , Humanos , Pandemias , Neumonía Viral , SARS-CoV-2 , Hipoclorito de SodioRESUMEN
PURPOSE: To evaluate clinical features and survival outcomes of uveal metastasis based on patient age. METHODS: Retrospective analysis of all patients with uveal metastasis evaluated on the Ocular Oncology Service, Wills Eye Hospital, Philadelphia, PA, USA between February 1, 1974 and June 1, 2017. The features and outcomes were analyzed based on patient age classified as children (0-20 years), young adults (21-40 years), middle [aged] adults (41-60 years), older adults (61-80 years) and senior adults (81-100 years). RESULTS: There were 1111 consecutive patients, including children (n = 3, <1%), young adults (n = 77, 7%), middle adults (n = 472, 42%), older adults (n = 509, 46%), and senior adults (n = 50, 4%). At uveal metastasis diagnosis, demographics included mean patient age of 60 years, Caucasian race (88%), and female gender (64%). Compared to the largest cohort (older adults), there were significant differences (age group versus [vs.] older adults) in Caucasian race (senior adult 98% vs. 89%, p = 0.042), male sex (young adults: 22% vs. 43%, p < 0.001) (middle adults: 29% vs. 43%, p < 0.001), unilateral tumor (young adult: 70% vs. 86%, p < 0.001) (middle adult: 79% vs. 86%, p = 0.003) (senior adults: 96% vs. 86%, p = 0.045), and cancer origin in breast (young adults: 51% vs. 32%, p = 0.002) (middle adults: 44% vs 32%, p < 0.001), lung (young adults: 14% vs. 30%, p = 0.004), kidney (young adults: 0% vs. 5%, p = 0.043), prostate (middle adults: 1% vs. 4%, p = 0.001), gastrointestinal tract (senior adults: 8% vs. 2%, p = 0.028), and others (children: 100% vs. 4%, p < 0.001) (young adults: 10% vs. 4%, p = 0.044). Kaplan-Meier survival (children, young, middle, older, and senior adults) at 1 year was 33%, 48%, 60%, 62%, and 76% and at 5 years was 0%, 22%, 29%, 25%, and 40%, respectively, with no difference per age category. The mean overall survival was 17.2 months and children demonstrated hazard ratio (HR) for death at 1 year of 2.1 relative to older adults. CONCLUSION: Uveal metastasis is found in all age groups. Compared to older adults, primary cancer site was more often breast and less likely lung in young and middle adults. Other rare sites were more often seen in children. Survival outcomes at 1 and 5 years were most favorable for senior adults and least favorable for children.
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Melanoma/secundario , Medición de Riesgo/métodos , Neoplasias de la Úvea/diagnóstico , Adolescente , Adulto , Distribución por Edad , Factores de Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Melanoma/diagnóstico , Melanoma/epidemiología , Persona de Mediana Edad , Metástasis de la Neoplasia , Pennsylvania/epidemiología , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Distribución por Sexo , Factores Sexuales , Neoplasias de la Úvea/epidemiología , Adulto JovenRESUMEN
PURPOSE: Retinoblastoma (Rb) is a potentially fatal intraocular malignancy in children, and hand-held optical coherence tomography (HH-OCT) can assist in submillimeter detection and monitoring after treatment of Rb. Retinoblastoma located in the macula, or those with chemoresistance, can be among the most difficult to manage. We describe HH-OCT features in a case of chemoresistant macular Rb that eventually responded to plaque radiotherapy after failing intravenous chemotherapy and intraarterial chemotherapy. METHODS: Observational case report. RESULTS: A 15-month-old girl with leukocoria was found to have Group D Rb in the right eye of 6-mm thickness and macular Group B Rb in the left eye of 4-mm thickness. She was treated with 6-monthly cycles of systemic intravenous chemotherapy and focal consolidation therapies to both eyes, with tumor regression in both eyes. However, macular tumor in the left eye demonstrated subsequent recurrence, from regressed thickness of 792 µm on HH-OCT to a dome-shaped hyperreflective retinal mass of >2000 µm thickness. Three cycles of intraarterial chemotherapy were sufficient for tumor regression down to 977 µm thickness on HH-OCT. Six months later, macular tumor in the left eye recurred again to >2000 µm thickness and necessitated plaque radiotherapy using apex dose of 35 Gy over 95.25 hours. Hand-held OCT confirmed rapid tumor regression to 722 µm after plaque treatment and regression remained stable at 6-month follow-up. CONCLUSION: Hand-held OCT was critical in assessment of Rb after failed intravenous chemotherapy and intraarterial chemotherapy and later documenting regression after plaque radiotherapy. Hand-held OCT is vital in providing cross-sectional imaging and measurements of small macular and paramacular Rbs.
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Neoplasias de la Retina/diagnóstico por imagen , Retinoblastoma/diagnóstico por imagen , Tomografía de Coherencia Óptica , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Braquiterapia , Carboplatino/uso terapéutico , Resistencia a Antineoplásicos , Etopósido/uso terapéutico , Femenino , Humanos , Lactante , Infusiones Intraarteriales , Infusiones Intravenosas , Neoplasias de la Retina/patología , Neoplasias de la Retina/terapia , Retinoblastoma/patología , Retinoblastoma/terapia , Vincristina/uso terapéuticoRESUMEN
PURPOSE: To investigate demographics and clinical features of patients with amelanotic choroidal tumours. DESIGN: Retrospective analysis. METHODS: Comparison of demographic and clinical features of various amelanotic choroidal tumours based on stratification by patient age, sex and tumour diameter. Included were all patients with amelanotic choroidal tumours evaluated on the Ocular Oncology Service, Wills Eye Hospital, Philadelphia, Pennsylvania, USA, over a 45-year time period. RESULTS: A total of 5586 amelanotic choroidal tumours in 4638 eyes of 4441 patients were included with a mean age at presentation of 58 years (median 60, range 0.1-100 years). Most patients were white (95%), female (56%) and with unilateral lesion (96%). By comparison, amelanotic melanoma presented at a younger mean age (57 years) compared with metastasis (60 years, p<0.001), nevus (61 years, p<0.001), lymphoma (65 years, p<0.001), sclerochoroidal calcification (70 years, p<0.001) and peripheral exudative haemorrhagic chorioretinopathy (80 years, p<0.001). Melanoma presented at an older mean age compared with osteoma (30 years, p<0.001), granuloma (42 years, p<0.001), haemangioma (49 years, p<0.001) and inflammatory choroidal lesions (49 years, p<0.001). Differences in race and sex were also seen between the various amelanotic choroidal lesions. With few exceptions, amelanotic melanoma had significantly larger basal diameter, greater thickness, more frequent association with subretinal fluid and more often ultrasonographically hollow, compared with other amelanotic choroidal lesions. CONCLUSION: Understanding the demographic and clinical features of amelanotic choroidal melanoma and other amelanotic lesions could lead to an earlier and more accurate diagnosis.
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Neoplasias de la Coroides/patología , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Coroides/patología , Femenino , Granuloma/patología , Hemangioma/patología , Humanos , Lactante , Linfoma/patología , Melanoma Amelanótico/patología , Persona de Mediana Edad , Nevo/patología , Osteoma/patología , Estudios Retrospectivos , Factores Sexuales , Adulto JovenRESUMEN
OBJECTIVES: To determine ocular outcomes and factors associated with adherence to ophthalmic follow-up in a medically underserved population at a single health centre in Philadelphia. DESIGN: Retrospective chart review. PARTICIPANTS: Patients from a community glaucoma screening program. METHODS: Chart review was conducted for participants who received a complete eye examination at the Philadelphia District Health Center 5 between January 1, 2012 and May 31, 2014 within the Philadelphia Glaucoma Detection and Treatment Project. Multivariate logistic regression was used to determine factors related to ophthalmic follow-up adherence. RESULTS: A total of 249 participants completed an eye examination (mean ageâ¯=â¯57.7 ± 6.9 years). Most were African American (nâ¯=â¯220; 88.4%); female (nâ¯=â¯129; 51.8%). Forty-seven participants (18.9%) received glaucoma-related diagnoses, 20 (8.0%) were prescribed ocular medication, and 26 (10.4%) underwent laser therapy. Ninety (36.1%) attended their recommended follow-up eye examination at the health centre. Glaucoma-related diagnosis (p ≤ 0.001), recommendation of a 4- to 6-week follow-up period (p < 0.001), prescribed eye drops (p < 0.001), or received laser therapy (pâ¯=â¯0.047) were factors most predictive of ophthalmic follow-up adherence. CONCLUSIONS: The collaborative effort of eye care providers and health centres offers an important opportunity to detect, treat, and manage glaucoma and other ocular pathology in medically underserved communities. Having a glaucoma-related diagnosis, initiating treatment, and scheduling regular follow-up visits are the most important factors influencing adherence to follow-up eye appointments.
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Servicios de Salud Comunitaria , Glaucoma de Ángulo Abierto/diagnóstico , Glaucoma de Ángulo Abierto/terapia , Cooperación del Paciente/estadística & datos numéricos , Adulto , Cuidados Posteriores , Anciano , Antihipertensivos/uso terapéutico , Servicios de Salud Comunitaria/métodos , Femenino , Estudios de Seguimiento , Glaucoma de Ángulo Abierto/fisiopatología , Humanos , Presión Intraocular/fisiología , Coagulación con Láser , Masculino , Área sin Atención Médica , Persona de Mediana Edad , Philadelphia , Estudios Retrospectivos , Tonometría Ocular , Trabeculectomía , Agudeza VisualRESUMEN
PURPOSE: To evaluate interval between primary cancer diagnosis and uveal metastasis and assess survival outcomes based on whether the primary cancer was diagnosed before or after uveal metastasis. METHODS: In this retrospective analysis, all patients with uveal metastasis evaluated on the Ocular Oncology Service, Wills Eye Hospital, Philadelphia, PA, USA between February 1, 1974 and June 1, 2017 were included. Features and outcomes based on timing of primary cancer diagnosis, whether before or after diagnosis of uveal metastasis, were assessed. RESULTS: A total of 2214 uveal metastases were diagnosed in 1310 eyes of 1111 consecutive patients. Primary cancer was known prior to uveal metastasis in 742 patients (67%) and not known in 369 (33%). Of those not known, the primary cancer was later found in 192 patients (17%) and never found in 177 patients (16%). For those with known primary cancer, mean interval from primary cancer diagnosis to uveal metastasis was 5.2â¯years with differences in primary sites of gastrointestinal (2.1â¯years, pâ¯=â¯0.003), lung (2.2â¯years, pâ¯<â¯0.001), breast (6.5â¯years, pâ¯<â¯0.001), and thyroid (13â¯years, pâ¯<â¯0.001). By Kaplan-Meier analysis, the 5-year overall survival showed no difference between patients with primary cancer found before (28%) vs after (20%) vs never found (33%), relative to uveal metastasis. CONCLUSION: Of 1111 patients with uveal metastasis, early-onset uveal metastases were found with lung and gastrointestinal tract cancers, whereas late-onset metastases were found with breast and thyroid cancers. Overall survival did not vary on whether the primary tumor was diagnosed before, after, or never found, relative to uveal metastasis.
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BACKGROUND: Lacking in previous studies on uveal metastasis is a robust statistical comparison of patient demographics, tumor features, and overall survival based on patient sex. OBJECTIVE: The aim of this study was to evaluate demographics, clinical features, and overall survival of patients with uveal metastasis based on sex. METHOD: This is a retrospective analysis. All patients were evaluated on the Ocular Oncology Service, Wills Eye Hospital, PA between January 1, 1974 and June 1, 2017. RESULTS: A total of 2214 uveal metastases were diagnosed in 1310 eyes of 1111 consecutive patients. A comparison (female versus male) revealed differences across several demographic and clinical features including, among others, mean age at metastasis diagnosis (58 vs 63 years, P < 0.001), bilateral disease (21% vs 11%, P < 0.001), and mean number of metastases per eye (1.8 vs 1.6 tumors per eye, P = 0.04). There were differences in overall mean survival (20 vs 13 months, Pâ=â0.03) and 5-year survival (Kaplan-Meier estimate) (31% vs 21%, P < 0.001). CONCLUSIONS: There are demographic, clinical, and survival differences when patients with uveal metastases are compared by sex. Understanding these differences can aid the clinician in better anticipating patient outcomes.
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Úvea/patología , Neoplasias de la Úvea/secundario , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Estudios de Seguimiento , Humanos , Masculino , Microscopía Acústica , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Estudios Retrospectivos , Distribución por Sexo , Factores Sexuales , Tasa de Supervivencia/tendencias , Estados Unidos/epidemiología , Neoplasias de la Úvea/diagnóstico , Neoplasias de la Úvea/mortalidad , Adulto JovenRESUMEN
BACKGROUND: Despite increasing evidence that adults with long-standing atopic dermatitis (AD) have systemic inflammation, little is known about systemic inflammation in recent-onset early pediatric AD. OBJECTIVE: To analyze blood inflammatory proteins of early pediatric AD. METHODS: Using high-throughput proteomics (proximity extension assay), we assessed 257 inflammatory and cardiovascular risk proteins in the blood of 30 children with moderate to severe AD younger than 5 years of age (within 6 months of onset) compared with age-matched pediatric control individuals and adult patients with AD. RESULTS: In pediatric AD blood, T helper (Th) type 2 (CCL13, CCL22) and Th17 (peptidase inhibitor-3/elafin) markers were increased, together with markers of tissue remodeling (matrix metalloproteinases 3/9/10, urokinase receptor), endothelial activation (E-selectin), T-cell activation (IL2RA), neutrophil activation (myeloperoxidase), lipid metabolism (FABP4), and growth factors (FGF21, transforming growth factor-α). Total numbers of dysregulated proteins were smaller in pediatric AD (n = 22) than in adult AD (n = 61). Clinical severity scores were positively correlated with receptors for interleukins 33 and 36 and inversely correlated with some Th1 markers (interferon gamma, CXCL11). LIMITATIONS: Different baseline expression levels in healthy pediatric vs adult samples. CONCLUSIONS: Within months of pediatric AD onset, systemic immune activation is present, with Th2/Th17 skewing but otherwise different proteomic patterns from adult AD. Future correlation of proteomic patterns with disease course, comorbidity development, and drug response may yield predictive biomarkers.
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Quimiocinas/sangre , Dermatitis Atópica/sangre , Elafina/sangre , Inflamación/sangre , Metaloproteinasas de la Matriz/sangre , Receptores de Interleucina/sangre , Factores de Edad , Biomarcadores/sangre , Estudios de Casos y Controles , Preescolar , Enfermedad Crónica , Dermatitis Atópica/metabolismo , Selectina E/sangre , Proteínas de Unión a Ácidos Grasos/sangre , Femenino , Factores de Crecimiento de Fibroblastos/sangre , Humanos , Lactante , Subunidad alfa del Receptor de Interleucina-2/sangre , Masculino , Peroxidasa/sangre , Proteoma/metabolismo , ARN Mensajero/metabolismo , Índice de Severidad de la Enfermedad , Factor de Crecimiento Transformador alfa/sangreRESUMEN
BACKGROUND: Atopic dermatitis (AD) shows differential clinical presentation in older compared with younger patients. Nevertheless, changes in the AD molecular profile with age are unknown. OBJECTIVE: We sought to characterize age-related changes in the AD profile. METHODS: We evaluated age-specific changes in lesional and nonlesional tissues and blood from patients with moderate-to-severe AD (n = 246) and age-matched control subjects (n = 71) using immunohistochemistry, quantitative real-time PCR, and Singulex in a cross-sectional study. Patients were analyzed by age group (18-40, 41-60, and ≥61 years). RESULTS: Although disease severity/SCORAD scores were similar across AD age groups (mean, approximately 60 years; P = .873), dendritic cell infiltrates (CD1b+ and FcεRI+, P < .05) decreased with age. TH2 measures (IL5, IL13, CCL13, CCL18, and CCL26) significantly decreased with age in patients with AD, despite increasing with age in control subjects. Consistent with TH2 axis decreases, serum IgE levels and eosinophil counts negatively correlated with age in patients with AD (r = -0.24 and r = -0.23, respectively; P < .05). TH22-secreted IL22 expression levels also decreased with age uniquely in patients with AD (P < .05). Expression of TH1-related (IFNG, IL12/23p40, STAT1, and CXCL9; P < .05 for CXCL9) and TH17-related (IL17A and IL20; P < .05 for IL20) markers increased with age in both patients with AD and control subjects. Expression of terminal differentiation measures significantly increased in older patients with AD (loricrin [LOR] and filaggrin [FLG], P < .05), whereas expression of S100As (S100A8, P < .01) and hyperplasia markers (epidermal thickness, keratin 16, and Ki67; P < .05 for keratin 16) decreased. Serum trends in AD mimicked skin findings, with TH2 downregulation (CCL26; r = -0.32, P < .1) and TH1 upregulation (IFN-γ; r = 0.48, P < .01) with age. CONCLUSION: The adult AD profile varies with age. Although TH1/TH17 skewing increases in both patients with AD and control subjects, patients with AD show unique decreases in TH2/TH22 polarization and normalization of epithelial abnormalities. Thus age-specific treatment approaches might be beneficial for AD.
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Envejecimiento , Dermatitis Atópica , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/sangre , Envejecimiento/genética , Envejecimiento/inmunología , Citocinas/genética , Citocinas/inmunología , Dermatitis Atópica/sangre , Dermatitis Atópica/genética , Dermatitis Atópica/inmunología , Dermatitis Atópica/patología , Femenino , Proteínas Filagrina , Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Índice de Severidad de la Enfermedad , Piel/inmunología , Piel/patología , Adulto JovenRESUMEN
A phase 2, double-blind, placebo-controlled trial evaluated apremilast efficacy, safety, and pharmacodynamics in adults with moderate to severe atopic dermatitis. Patients were randomly assigned to receive placebo, apremilast 30 mg twice daily (APR30), or apremilast 40 mg twice daily (APR40) for 12 weeks. During weeks 12-24, all patients received APR30 or APR40. A biopsy substudy evaluated atopic dermatitis-related biomarkers. Among 185 randomly assigned intent-to-treat patients at week 12, a dose-response relationship was observed; APR40 (n = 63), but not APR30 (n = 58), led to statistically significant improvements (vs. placebo, n = 64) in Eczema Area and Severity Index (mean [standard deviation] percent change from baseline = -31.6% [44.6] vs. -11.0% [71.2], P < 0.04; primary endpoint). mRNA expression of T helper type 17/T helper type 22-related markers (IL-17A, IL-22, and S100A7/A8; P < 0.05) showed the highest reductions with APR40, with minimal changes in other immune axes. Safety with APR30 was largely consistent with apremilast's known profile (common adverse events: nausea, diarrhea, headache, and nasopharyngitis). With APR40, adverse events were more frequent, and cellulitis occurred (n = 6). An independent safety monitoring committee discontinued the APR40 dosage. APR40 showed modest efficacy and decreased atopic dermatitis-related biomarkers in moderate to severe atopic dermatitis patients. Adverse events, including cellulitis, were more frequent with APR40, which was discontinued during the trial. Clinical Trial Registration Number: NCT02087943 (clinicaltrials.gov).