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1.
Am J Pathol ; 194(1): 150-164, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37827217

RESUMEN

Corneal endothelial cells (CEnCs) regulate corneal hydration and maintain tissue transparency through their barrier and pump function. However, these cells exhibit limited regenerative capacity following injury. Currently, corneal transplantation is the only established therapy for restoring endothelial function, and there are no pharmacologic interventions available for restoring endothelial function. This study investigated the efficacy of the neuropeptide α-melanocyte-stimulating hormone (α-MSH) in promoting endothelial regeneration during the critical window between ocular injury and the onset of endothelial decompensation using an established murine model of injury using transcorneal freezing. Local administration of α-MSH following injury prevented corneal edema and opacity, reduced leukocyte infiltration, and limited CEnC apoptosis while promoting their proliferation. These results suggest that α-MSH has a proregenerative and cytoprotective function on CEnCs and shows promise as a therapy for the prevention and management of corneal endothelial dysfunction.


Asunto(s)
Córnea , Edema Corneal , alfa-MSH , Femenino , Embarazo , Animales , Ratones , Ratones Endogámicos BALB C , Humanos , Línea Celular , Córnea/citología , Células Endoteliales , Edema Corneal/tratamiento farmacológico , Edema Corneal/patología , Conservación de Tejido , alfa-MSH/uso terapéutico , Citoprotección , Infiltración Neutrófila , Monocitos/metabolismo , Macrófagos/metabolismo , Cicatrización de Heridas/efectos de los fármacos
2.
Ophthalmology ; 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38986874

RESUMEN

PURPOSE: Vision loss associated with opacification of the cornea is one of the leading causes of blindness globally. However, the epidemiological data pertaining to the demographics, associated etiological causes and reduced vision in corneal opacity patients continue to be sparse. This study assesses the case frequencies, underlying etiologies, and vision outcomes in patients diagnosed with corneal opacity, in the United States. DESIGN: Retrospective cohort study PARTICIPANTS: Patients in the IRIS® Registry (Intelligent Research in Sight) who were diagnosed with corneal opacity between January 1st, 2013, and November 30th, 2020. METHODS: The IRIS Registry contains demographic and clinical data of 79,887,324 patients who presented to eye clinics during the study period. We identified patients with corneal opacity using International Classification of Disease (ICD) codes (ICD-9, and -10) of "371" (corneal scar) and "H17" (corneal opacity), respectively. The analyzed data included demographic parameters included age, sex, race, ethnicity, and geographical location. We evaluated clinical data including laterality, etiology, disease descriptors, and best-corrected visual acuity (VA) up to 1 year before the onset (± 30 days), at the time of diagnosis, and at one year following diagnosis (± 30 days). MAIN OUTCOME MEASURES: Case frequencies, etiology, and vision outcomes in patients diagnosed with corneal opacity. RESULTS: We identified 5,220,382 patients who were diagnosed with corneal opacity and scars using H17 (ICD-10) and 371.0 (ICD-9) codes over seven years. The case frequency of corneal opacity during the study period was 6,535 cases per 100,000 patients (6.5%). The mean age of the patients was 63.36±18.14 years and the majority were female (57.6%). In the cohort, 38.39% and 30.00% of patients had bilateral and unilateral corneal opacity, respectively. Most of the patients were White (69.13%), followed by Black or African American (6.84%), Asian (2.45%), American Indian or Alaska Native(0.34%), Native Hawaii or other Pacific Islander(0.19%). Among the patients with corneal opacity, 7.34% had Hispanic or Latino ethnicity. The primary etiologies associated with corneal opacity included corneal dystrophies (64.66%) followed by edema (18.25%), ulcer (7.78%), keratoconjunctivitis (7.18%), degeneration (5.62%), neovascularization (6.27%), and trauma (5.28%). Visual acuity of the patients significantly worsened due to corneal opacity (0.46±0.74 logMAR; ∼20/58 in Snellen) and did not improve to the baseline (0.37±0.68 logMAR, ∼20/46 in Snellen) post-management (0.43±0.77 logMAR, ∼20/54 in Snellen). The multiple linear regression analysis showed worse vision outcomes in females (compared to males), and Asian, Black or African American, and American Indian or Alaska Native (compared to White) patients. Additionally, worse vision outcomes were observed in patients with opacity associated with corneal malformation, degenerative disorders, edema, injury, and ulcer compared to those with hereditary corneal dystrophy. CONCLUSIONS: Our study shows that the corneal opacity was diagnosed in 6.5% of the patients in the IRIS Registry and it was primarily associated with corneal dystrophies. The final vision outcomes in corneal opacity patients were significantly worse compared to baseline. The worse vision outcomes were associated with sociodemographic differences that might be associated with disparities in access, utilization, and care patterns.

3.
Exp Eye Res ; 242: 109871, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38527580

RESUMEN

Myeloid derived suppressor cells (MDSCs) are a heterogenous population of immature hematopoietic precursors with known immunoregulatory functions. The immunosuppressive role of MDSCs has been highlighted in several inflammatory ophthalmic disorders; however, their therapeutic application in suppressing the immune-mediated changes in dry eye disease (DED) has not been studied. We observed significant reduction in antigen presenting cell (APC) frequencies and their maturation in the presence of MDSCs. Moreover, co-culturing MDSCs with T helper 17 cells (Th17) resulted in reduced Th17 frequencies and their IL-17 expression. On the contrary, MDSCs maintained regulatory T cell frequencies and enhanced their function in-vitro. Furthermore, we delineated the role of interleukin-10 (IL-10) secreted by MDSCs in their immunoregulatory functions. We confirmed these results by flow cytometry analysis and observed that treatment with MDSCs in DED mice effectively suppressed the maturation of APCs, pathogenic Th17 response, and maintained Treg function and significantly ameliorated the disease. The results in this study highlight the potential therapeutic application of MDSCs in treating refractory DED.


Asunto(s)
Modelos Animales de Enfermedad , Síndromes de Ojo Seco , Citometría de Flujo , Ratones Endogámicos C57BL , Células Supresoras de Origen Mieloide , Linfocitos T Reguladores , Células Th17 , Animales , Células Supresoras de Origen Mieloide/inmunología , Síndromes de Ojo Seco/inmunología , Síndromes de Ojo Seco/metabolismo , Ratones , Células Th17/inmunología , Linfocitos T Reguladores/inmunología , Células Presentadoras de Antígenos/inmunología , Femenino , Progresión de la Enfermedad , Interleucina-10/metabolismo , Células Cultivadas , Técnicas de Cocultivo
4.
Exp Eye Res ; : 110006, 2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39009059

RESUMEN

Regulatory T cells (Tregs) play a critical role in maintaining immune homeostasis, and their dysfunction is implicated in the pathogenesis of various autoimmune disorders, including dry eye disease (DED). Treg dysfunction in DED allows T-helper cell 17 (Th17) mediated chronic inflammation at the ocular surface. In this study, the factors causing Treg dysfunction in DED were investigated. We observed reduced expression of Treg functional markers - FoxP3, CD25, and CTLA-4 in the cells isolated from DED mice (DED Tregs). Additionally, DED Tregs showed increased expression levels of receptors for pro-inflammatory cytokine receptors, namely IL-6R, IL-17RA, and IL-23R. An increased expression level of pro-inflammatory cytokine receptors was observed on exposing Tregs isolated from naïve mice (NTregs) to IL-6 or IL-17, but not IL-23, with a concomitant downregulation of FoxP3, CD25, and CTLA-4 in these cells. Furthermore, among these cytokines, IL-6 induced the most pronounced loss of Treg mediated suppression of Th17 proliferation and IL-10 secretion. In vitro and in vivo blockade of IL-6 effectively restored function in DED Tregs, leading to enhanced suppressive function against proliferating Th17 cells and ameliorating disease severity. In conclusion, this study provides insights into mechanisms of Treg dysregulation in DED, specifically delineating the effect of Th17-associated cytokines, with IL-6 emerging as the critical factor inducing Treg dysfunctionality. These findings highlight the potential for developing novel therapeutic interventions for DED through restoration of immunosuppressive function of Tregs.

5.
Medicina (Kaunas) ; 60(4)2024 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-38674173

RESUMEN

Artificial intelligence (AI) has emerged as a transformative tool in the field of ophthalmology, revolutionizing disease diagnosis and management. This paper provides a comprehensive overview of AI applications in various retinal diseases, highlighting its potential to enhance screening efficiency, facilitate early diagnosis, and improve patient outcomes. Herein, we elucidate the fundamental concepts of AI, including machine learning (ML) and deep learning (DL), and their application in ophthalmology, underscoring the significance of AI-driven solutions in addressing the complexity and variability of retinal diseases. Furthermore, we delve into the specific applications of AI in retinal diseases such as diabetic retinopathy (DR), age-related macular degeneration (AMD), Macular Neovascularization, retinopathy of prematurity (ROP), retinal vein occlusion (RVO), hypertensive retinopathy (HR), Retinitis Pigmentosa, Stargardt disease, best vitelliform macular dystrophy, and sickle cell retinopathy. We focus on the current landscape of AI technologies, including various AI models, their performance metrics, and clinical implications. Furthermore, we aim to address challenges and pitfalls associated with the integration of AI in clinical practice, including the "black box phenomenon", biases in data representation, and limitations in comprehensive patient assessment. In conclusion, this review emphasizes the collaborative role of AI alongside healthcare professionals, advocating for a synergistic approach to healthcare delivery. It highlights the importance of leveraging AI to augment, rather than replace, human expertise, thereby maximizing its potential to revolutionize healthcare delivery, mitigate healthcare disparities, and improve patient outcomes in the evolving landscape of medicine.


Asunto(s)
Inteligencia Artificial , Diagnóstico Precoz , Enfermedades de la Retina , Humanos , Enfermedades de la Retina/diagnóstico , Retinopatía Diabética/diagnóstico , Aprendizaje Automático , Aprendizaje Profundo , Degeneración Macular/diagnóstico
6.
JAAPA ; 37(1): 1-6, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38128142

RESUMEN

ABSTRACT: Cutaneous squamous cell carcinoma can arise from various premalignant lesions such as actinic keratosis, Bowen disease, and premalignant genital squamous cell lesions. Identification and treatment can prevent malignant transformation and death. This article describes the causes, epidemiology, and characteristics of suspicious premalignant squamous cell lesions so that clinicians can identify these lesions and refer patients for specialist treatment as appropriate.


Asunto(s)
Carcinoma de Células Escamosas , Queratosis Actínica , Neoplasias Cutáneas , Humanos , Queratosis Actínica/diagnóstico , Queratosis Actínica/epidemiología , Queratosis Actínica/terapia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/etiología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/epidemiología , Neoplasias Cutáneas/etiología
7.
Am J Transplant ; 23(9): 1345-1358, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37245642

RESUMEN

Corneal transplantation is the most common form of solid tissue grafting, with an approximately 80% to 90% success rate. However, success rates may decline when donor tissues are derived from patients with a history of diabetes mellitus (DM). To evaluate the underlying immunopathologic processes that cause graft rejection, we used streptozotocin-induced type 1 DM (DM1) and transgenic Lepob/ob type 2 DM (DM2) diabetic murine models as donors and nondiabetic BALB/c as recipients. DM resulted in an increased frequency of corneal antigen-presenting cells (APCs) with an acquired immunostimulatory phenotype. Following transplantation, recipients that received either type of diabetic graft showed increased APC migration and T helper type 1 alloreactive cells, impaired functional regulatory T cells, and graft survival. Insulin treatment in streptozotocin-induced diabetic mice led to an increased tolerogenic profile of graft APC, lower T helper type 1 sensitization, and a higher frequency of functional regulatory T cells with high suppressive capacity, reflected in increased graft survival. We conclude that both DM1 and DM2 in donors can impact corneal APC functional phenotype, rendering the tissue more immunogenic and thereby increasing the risk of graft failure.


Asunto(s)
Trasplante de Córnea , Diabetes Mellitus Experimental , Animales , Ratones , Diabetes Mellitus Experimental/cirugía , Diabetes Mellitus Experimental/patología , Estreptozocina , Córnea , Células Presentadoras de Antígenos
8.
Ophthalmology ; 130(2): 179-186, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36055601

RESUMEN

PURPOSE: To assess the risk of vaccine-associated uveitis (VAU) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and evaluate uveitis onset interval and clinical presentations in the patients. DESIGN: A retrospective study from December 11, 2020, to May 9, 2022, using the Centers for Disease Control and Prevention Vaccine Adverse Event Reporting System. PARTICIPANTS: Patients diagnosed with VAU after administration of BNT162b2 (Pfizer-BioNTech, Pfizer Inc/BioNTech SE), mRNA-1273 (Moderna, Moderna Therapeutics Inc), and Ad26.COV2.S (Janssen, Janssen Pharmaceuticals) vaccine worldwide. METHODS: A descriptive analysis of the demographics, clinical history, and presentation was performed. We evaluated the correlation among the 3 vaccines and continuous and categorical variables. A post hoc analysis was performed between uveitis onset interval after vaccination and age, dose, and vaccine type. Finally, a 30-day risk analysis for VAU onset postvaccination was performed. MAIN OUTCOME MEASURES: The estimated global crude reporting rate, observed to expected ratio of VAU in the United States, associated ocular and systemic presentations, and onset duration. RESULTS: A total of 1094 cases of VAU were reported from 40 countries with an estimated crude reporting rate (per million doses) of 0.57, 0.44, and 0.35 for BNT162b2, mRNA-1273, and Ad26.COV2.S, respectively. The observed to expected ratio of VAU was comparable for BNT162b2 (0.023), mRNA-1273 (0.025), and Ad26.COV2.S (0.027). Most cases of VAU were reported in patients who received BNT162b2 (n = 853, 77.97%). The mean age of patients with VAU was 46.24 ± 16.93 years, and 68.65% (n = 751) were women. Most cases were reported after the first dose (n = 452, 41.32%) and within the first week (n = 591, 54.02%) of the vaccination. The onset interval for VAU was significantly longer in patients who received mRNA-1273 (21.22 ± 42.74 days) compared with BNT162b2 (11.42 ± 23.16 days) and rAd26.COV2.S (12.69 ± 16.02 days) vaccines (P < 0.0001). The post hoc analysis revealed a significantly shorter interval of onset for the BNT162b2 compared with the mRNA 1273 vaccine (P < 0.0001). The 30-day risk analysis showed a significant difference among the 3 vaccines (P < 0.0001). CONCLUSIONS: The low crude reporting rate and observed to expected ratio suggest a low safety concern for VAU. This study provides insights into a possible temporal association between reported VAU events and SARS-CoV-2 vaccines; however, further investigations are required to delineate the associated immunological mechanisms.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Uveítis , Vacunas , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vacuna nCoV-2019 mRNA-1273 , Ad26COVS1 , Vacuna BNT162 , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Estudios Retrospectivos , SARS-CoV-2 , Uveítis/epidemiología , Uveítis/etiología , Vacunación/efectos adversos
9.
FASEB J ; 36(8)2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35781326

RESUMEN

Regulation of innate inflammation is critical for maintaining tissue homeostasis and barrier function, especially in those interfacing the external environments such as the skin and cornea. Expression of pro-inflammatory cytokines by injured tissues has been shown to exacerbate the inflammatory cascade, causing tissue damage. Interleukin 36, a subfamily of the IL-1 superfamily, consists of three pro-inflammatory agonists-IL36α, IL36ß, and IL36γ and an IL36 receptor antagonist (IL36Ra). The current investigation, for the first time, reports that IL36γ is the primary agonist expressed by the corneal epithelium, which is significantly upregulated following corneal injury. The function of IL36γ on non-immune cells, in addition to innate inflammatory cells, in regulating tissue homeostasis has not been well investigated. Using a loss-of-function approach via neutralizing antibody treatment, our data demonstrate that blocking endogenously expressed IL36γ in epithelial cells promotes rapid re-epithelialization in in vitro wound closure assay. Finally, by utilizing a naturally occurring antagonist IL36Ra in a well-established murine model of ocular injury, our study demonstrates that inhibition of IL36γ accelerates epithelial regeneration and suppresses tissue inflammation. Given rapid wound healing is critical for re-establishing normal tissue structure and function, our investigation on the function of IL36γ provides evidence for the development of novel IL36γ-targeting strategies to promote tissue repair.


Asunto(s)
Córnea/fisiología , Interleucina-1/metabolismo , Animales , Epitelio Corneal/fisiología , Inflamación/inmunología , Interleucina-1/inmunología , Ratones , Cicatrización de Heridas
10.
Ann Pharmacother ; 57(2): 207-216, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-35674400

RESUMEN

OBJECTIVE: To review the pharmacokinetics, efficacy, and safety of a newly approved topical Janus kinase 1 (JAK) inhibitor, ruxolitinib (RUX), in patients with atopic dermatitis (AD). DATA SOURCES: A literature search was completed May 1, 2022. The term RUX and AD was queried in MEDLINE (PubMed) and EMBASE databases. STUDY SELECTION AND DATA EXTRACTION: Peer-reviewed articles written in English and published prior to May 1, 2022 were included. DATA SYNTHESIS: In the phase II clinical trial, more patients treated with 1.5% topical RUX twice a day had a mean percentage improvement in Eczema Area and Severity Index (EASI) scores from baseline to 4 weeks, when compared to vehicle (71.6% vs 15.5%; P < 0.001). In phase III clinical trials, greater percentage of patients who received 0.75% topical RUX (TRuE-AD1 50.0% and TRuE-AD2 39.0%) or 1.5% topical RUX (TRuE-AD1 53.8% and TRuE-AD2 51.3%) achieved an Investigator's Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) and had a ≥2-grade improvement from baseline to 8 weeks, when compared to vehicle (TRuE-AD1 15.1% and TRuE-AD2 7.6%; P < 0.001). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Atopic dermatitis is a highly prevalent long-term inflammatory skin condition. Pruritus is the main contributor of decreased quality of life in patients with AD. Topical RUX inhibits JAK1 and JAK2 producing antiinflammatory and antipruritic effects. Patients experienced a reduction in pruritus within 2 days. This decreased pruritus translated to increased quality of life and less sleep disturbances. CONCLUSION: Data from phase II and III clinical trials in adult patients suggest RUX is an effective and safe therapy for AD.


Asunto(s)
Dermatitis Atópica , Inhibidores de las Cinasas Janus , Adulto , Humanos , Dermatitis Atópica/tratamiento farmacológico , Calidad de Vida , Resultado del Tratamiento , Método Doble Ciego , Prurito/tratamiento farmacológico , Inhibidores de las Cinasas Janus/efectos adversos , Índice de Severidad de la Enfermedad
11.
Ann Pharmacother ; 57(3): 341-347, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-35730211

RESUMEN

OBJECTIVE: To review the pharmacokinetics, efficacy, and safety of recently approved calcipotriene and betamethasone dipropionate (C-BD) cream. DATA SOURCES: A literature review was conducted using MEDLINE (PubMed) and ClinicalTrials.gov from 2002 to mid-May 2022. STUDY SELECTION AND DATA EXTRACTION: Articles in English discussing the use of C-BD cream in the treatment of psoriasis were included. DATA SYNTHESIS: In 2 phase I trials, there was no phototoxic or photoallergic skin reaction at irradiated C-BD cream sites at baseline, 24 hours, 48 hours, and 72 hours postirradiation. In 2 phase III trials, after 8 weeks of treatment, more subjects treated with C-BD cream achieved Physician's Global Assessment treatment success (37.4%), compared to C-BD topical suspension (TS) (22.8%, P < 0.0001) and vehicle (3.7%, P < 0.0001). More subjects had greater mean percentage decline in Modified Psoriasis Area Severity Index (Trial 1: 52.9% and Trial 2: 64.6%), when compared to C-BD TS (Trial 1: 51.3%, P < 0.0001 and Trial 2: 56.4%, P < 0.0001) and vehicle (Trial 1: 22.9%, P < 0.0001 and Trial 2: 20.0%, P < 0.0001). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Psoriasis has a multifactorial pathogenesis and topical treatments are considered first line. Poor adherence is a major hurdle in management; the combination of 2 separate first-line drugs may address this by decreasing the complexity of treatment regimens. A cream formulation can be preferred, and C-BD is now Food and Drug Administration (FDA) approved as one. CONCLUSIONS: Newly FDA-approved C-BD cream with novel polyaphron dispersion (PAD) technology provides a safe efficacious combination therapy for mild-to-moderate psoriasis which may be preferred by some patients.


Asunto(s)
Fármacos Dermatológicos , Psoriasis , Humanos , Fármacos Dermatológicos/efectos adversos , Combinación de Medicamentos , Psoriasis/tratamiento farmacológico , Betametasona/efectos adversos , Resultado del Tratamiento
12.
Ann Pharmacother ; 57(3): 333-340, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-35730479

RESUMEN

OBJECTIVE: To review pharmacokinetics, efficacy, and safety of tralokinumab in treatment of atopic dermatitis (AD). DATA SOURCES: Literature review was conducted using MEDLINE (PubMed), EMBASE, and ClinicalTrials.gov for articles published between January 2010 and May 2022. STUDY SELECTION AND DATA EXTRACTION: Articles in English discussing tralokinumab in AD were included. DATA SYNTHESIS: In one phase 2 trial, more subjects treated with tralokinumab 150 and 300 mg achieved an Investigator's Global Assessment (IGA) of 0/1 with minimum ≥2 point IGA reduction (23%), versus placebo (11.8%, P = 0.10). During 2 phase 3 trials, more subjects treated with tralokinumab achieved IGA success (ECZTRA 1: 15.8% and ECZTRA 2: 22.2%), versus placebo (7.1% and 10.9%, respectively; P = 0.002 and P < 0.001). During one phase 3 trial, in conjunction with topical corticosteroids (TCS), more subjects treated with tralokinumab 300 mg achieved IGA success (ECZTRA 3: 38.9%), versus placebo (26.2%, P = 0.015). During another phase 3 trial in subjects with resistance or contraindication to oral cyclosporine, more subjects treated with tralokinumab 300 mg achieved an Eczema Area Severity Index 75 (64.2%), versus placebo (50.5%, P = 0.018). RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Tralokinumab is efficacious for moderate-to-severe AD, as monotherapy, in conjunction with TCS, and resistance or contraindication to cyclosporine. Although IL-4 and IL-13 are both implicated in AD's pathogenesis, IL-13 is overexpressed, and head-to-head trials are needed to assess efficacy of tralokinumab, versus dupilumab. Compared with upadacitinib and abrocitinib, tralokinumab is not associated with black-box warnings. CONCLUSIONS: Tralokinumab is an efficacious and safe systemic treatment for moderate-to-severe AD.


Asunto(s)
Dermatitis Atópica , Fármacos Dermatológicos , Humanos , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/complicaciones , Dermatitis Atópica/patología , Interleucina-13/uso terapéutico , Resultado del Tratamiento , Método Doble Ciego , Índice de Severidad de la Enfermedad , Glucocorticoides/uso terapéutico , Ciclosporina/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Inmunoglobulina A/uso terapéutico
13.
Clin Exp Dermatol ; 48(4): 371-373, 2023 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-36763729

RESUMEN

Calciphylaxis is a debilitating disease associated with high mortality and morbidity secondary to pain, nonhealing wounds and frequent hospital admissions. We qualitatively assessed the burden of calciphylaxis on patient quality of life through semi-structured interviews with nine adult participants. Participants identified an inability to complete activities of daily living because of mobility impairment and decreased strength, although most denied complete dependence on others. All participants described pain as the worst aspect of disease, citing a variable course, unpredictability in severity and poor control despite medical therapy. Calciphylaxis also caused feelings of sadness and anger, having a negative impact on self-confidence. Supportive care needs to address the pervasive and severe nature of pain, mobility impairment and psychiatric comorbidities; such interventions may decrease the overall burden for patients with calciphylaxis.


Asunto(s)
Calcifilaxia , Adulto , Humanos , Calcifilaxia/complicaciones , Calidad de Vida , Actividades Cotidianas , Diálisis Renal/efectos adversos , Dolor/etiología
14.
J Drugs Dermatol ; 22(9): 935-940, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37683061

RESUMEN

BACKGROUND: Alopecia areata (AA) is a debilitating autoimmune disease that results in non-scarring hair loss. Baricitinib is the Food and Drug Administration (FDA) approved treatment for AA.  Objective: Review the mechanism of action, pharmacokinetics, pharmacodynamics, efficacy, and safety of baricitinib in the treatment of AA.  Methods: A literature review was conducted using the MEDLINE (PubMed) and EMBASE databases for articles published between January 2010 to November 2022. Articles in English discussing baricitinib's efficacy and safety in AA, pharmacodynamic, and pharmacokinetic profiles were included. RESULTS: Two identical phase III trials (BRAVE-AA1 and BRAVE-AA2) were evaluated. A greater percentage of subjects receiving baricitinib 4 mg or 2 mg dose achieved a Severity of Alopecia Tool score equal to or less than 20 vs placebo. In BRAVE-AA1, for 4 mg, 2 mg, and placebo, respectively, these values were 38.8%, 22.8%, and 6.2%; in BRAVE-AA2, these values were 35.9%, 19.4%, and 3.3% (P<0.001). DISCUSSION: Baricitinib is the first FDA-approved treatment for AA. Other treatments for AA are used off-label with variable efficacy. Baricitinib is associated with black-box warnings due to adverse effects (AEs) associated with other Janus Kinase (JAK) inhibitors or use in other diseases. In the two large AA trials, AEs were considered mild or moderate; those reported more often with baricitinib than placebo included acne, elevations of low- and high-density lipoprotein cholesterol, and elevation of creatinine kinase. Baricitinib is a relatively tolerable and safe therapeutic alternative for severe AA, although additional study is needed to assess its long-term efficacy and safety.  Citation: Singh R, Driscoll MS. Review of baricitinib in the treatment of alopecia areata. J Drugs Dermatol. 2023;22(9):935-939. doi:10.36849/JDD.7357.


Asunto(s)
Alopecia Areata , Azetidinas , Inhibidores de las Cinasas Janus , Estados Unidos , Humanos , Alopecia Areata/diagnóstico , Alopecia Areata/tratamiento farmacológico , Azetidinas/efectos adversos , Purinas/efectos adversos , Inhibidores de las Cinasas Janus/efectos adversos
15.
J Drugs Dermatol ; 22(2): 148-153, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36745376

RESUMEN

BACKGROUND: Atopic dermatitis (AD) is the most common inflammatory skin disease and dupilumab is US Food and Drug Administration-approved in both adult and pediatric AD patients. OBJECTIVE: To qualitatively assess the life experiences and impact of treatment in adult and adolescent patients with AD being treated with dupilumab. METHODS: Sixteen semi-structured interviews were conducted with adult (n=9) and adolescent (n=7) participants who had received a diagnosis of AD between 1/1/2017 and 1/1/2022 after they had received treatment with dupilumab. Results were analyzed using qualitative research methods. RESULTS: Most participants reported frustration with daily topical medications and starting dupilumab after exhausting other treatment options. Before treatment, participants described severe AD, social anxiety, and decreased self-esteem. Although most participants did not experience complete resolution of AD after treatment, all participants described a profound decrease in the physical and psychosocial burden of their disease. Participant satisfaction was high with dupilumab treatment. Injection-related pain was commonly reported as the most negative aspect of treatment. DISCUSSION: AD was physically and psychosocially debilitating in our cohort. Dupilumab offered an efficacious treatment for these patients and helped improve the physical and psychosocial burden of their disease. J Drugs Dermatol. 2023;22(2):148-153. doi:10.36849/JDD.7053.


Asunto(s)
Dermatitis Atópica , Humanos , Adulto , Adolescente , Niño , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/psicología , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Método Doble Ciego , Reacción en el Punto de Inyección , Dolor , Investigación Cualitativa
16.
J Drugs Dermatol ; 22(8): 838-839, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37556519

RESUMEN

Improved patient-physician relationships (PPR) are associated with better patient satisfaction and disease outcomes, however, there is limited literature assessing how PPR affects adherence in dermatology. We recruited 30 subjects with a clinical diagnosis of rosacea. Subjects were instructed to use ivermectin 1% cream once daily for 3 months and adherence was measured using the Medication Event Monitoring System cap. The Patient-Doctor Relationship Questionnaire (PDRQ-9), a validated questionnaire assessing patients’ perceived strength of the relationship with their doctor, was completed. Mean adherence for all subjects over three months of the study was 62%. PDRQ-9 scores positively correlated with adherence rates for 3 months of treatment (r(26)=0.52; P=0.006). The perceived strength of the PPR may have a role in patients’ adherence to their medications. Improving the PPR, through empathy and effective communication, may facilitate better medication adherence and treatment outcomes. Perche PO, Singh R, Cook MK, et al. The patient-physician relationship and adherence: observations from a clinical study. J Drugs Dermatol. 2023;22(8):838-839. doi:10.36849/JDD.7103.


Asunto(s)
Médicos , Rosácea , Humanos , Rosácea/tratamiento farmacológico , Resultado del Tratamiento , Satisfacción del Paciente , Ivermectina , Cumplimiento de la Medicación
17.
J Drugs Dermatol ; 22(12): e51-e52, 2023 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-38051832

RESUMEN

BACKGROUND: Repairing the epidermal barrier is critically important in atopic dermatitis (AD), but the effect of moisturizer on quality of life (QOL) is not well characterized.  Objective: To assess whether the use of a moisturizer improves QOL in atopic patients with xerosis.  Methods: Thirty-five (35) adults with xerosis and AD received a moisturizer designed for AD to apply daily for three months. Adherence was assessed with electronic monitors. Quality of life (QOL) was assessed with the Dermatology Life Quality Index (DLQI) at baseline and follow-up.  Results: Mean adherence to the moisturizer was 46%. Dryness improved from 1.9 at baseline to 1.4 at follow-up (P=0.02). DLQI improved from 3.3 at baseline to 1.5 at 3 months (P=0.005). The "feeling self-conscious or embarrassed due to their skin condition" DLQI item improved from 0.79 at baseline to 0.14 at 3 months (P=0.0009).  Conclusion: Moisturizers are the foundation of AD treatment. Even non-medicated topical emollients can improve QOL in patients with AD.  J Drugs Dermatol. 2023;22(12):e51-e52.     doi:10.36849/JDD.7036e.


Asunto(s)
Dermatitis Atópica , Enfermedades Gastrointestinales , Adulto , Humanos , Calidad de Vida , Emolientes , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/tratamiento farmacológico , Epidermis , Gravedad del Paciente , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
18.
J Drugs Dermatol ; 22(10): 1063-1064, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37801528

RESUMEN

Rosacea has variable clinical presentation consisting of four overlapping phenotypes: erythematotelangiectatic, papulopustular, phymatous, and ocular.1 Rosacea's pathogenesis involves increased cutaneous density of Demodex folliculorum mites, which drive inflammation through activation of Toll-like receptor-2.1,2 Thus, topical ivermectin (IVM) 1.0% cream's anti-inflammatory and acaricidal activity provides an effective and targeted treatment for moderate-to-severe rosacea. However, literature assessing IVM is limited to efficacy in treating the papulopustular presentation, limiting generalizability.1,3,4 Although our primary endpoint was to assess patient adherence, the objective of this secondary analysis was to assess IVM efficacy in rosacea, regardless of clinical presentation.


Asunto(s)
Ivermectina , Rosácea , Humanos , Ivermectina/uso terapéutico , Rosácea/diagnóstico , Rosácea/tratamiento farmacológico , Rosácea/patología , Piel/patología , Administración Cutánea , Antiinflamatorios/uso terapéutico
19.
Int Ophthalmol ; 43(6): 2037-2047, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36445547

RESUMEN

OBJECTIVE: To determine the ability of the Internet-based Spaeth/Richman Contrast Sensitivity (SPARCS) in assessing the change in contrast sensitivity (both central and peripheral) post-treatment with travoprost 0.004%. DESIGN: This is a prospective observational study. METHODS AND PARTICIPANTS: Data of 62 eyes (33 patients) undergoing treatment for naïve POAG patients were analysed. Patients were followed up for a period of six months after starting topical travoprost (Travatan 0.004%, Alcon), and the change in central and peripheral CS was studied. RESULTS: Mean total SPARCS score at baseline was 69 ± 10.99, improved to 74.62 ± 9.50 after 6 months of therapy (p: 0.001) in all the glaucoma severity groups. Mean SPARCS score at baseline in mild glaucoma group was 72.05 ± 9.87, in the moderate glaucoma group, it was 62.23 ± 9.2, and in the severe glaucoma group, it was 59.36 ± 11.65. After 6 months of treatment with travoprost, the CS improved to 76.05 ± 8.36 in mild group, 76.69 ± 8.82 in moderate group and 67.18 ± 11.15 in severe group (p value: 0.014). The percentage change in the CS from baseline showed significant improvement in the superotemporal quadrant at 1 month (p value: 0.032), superonasal quadrant (p value: 0.049), inferotemporal quadrant at 3 months (p value: 0.003) and 6 months (p value: 0.039). Inferonasal quadrant was affected most by glaucoma. A statistically significant correlation was seen between total SPARCS score with MD and PSD. Correlation was also seen between the percentage change in CS and average RNFL thickness at 3 and 6 months. CONCLUSION: Both central and peripheral CS improve following IOP reduction with travoprost. Change in the CS has a significant correlation with RNFL thickness and the perimetric indices.


Asunto(s)
Glaucoma de Ángulo Abierto , Glaucoma , Humanos , Travoprost/uso terapéutico , Sensibilidad de Contraste , Glaucoma de Ángulo Abierto/tratamiento farmacológico , Pruebas de Visión/métodos , Glaucoma/tratamiento farmacológico , Presión Intraocular , Antihipertensivos/uso terapéutico
20.
Int Ophthalmol ; 43(9): 3425-3432, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37191927

RESUMEN

PURPOSE: The use of video-based social media platforms is increasing among trainee residents, fellows, and practicing ophthalmologists. In this study, we objectively evaluate the quality of Ahmed glaucoma valve (AGV) implantation videos on open access, video-based internet platforms. DESIGN: Internet-based cross-sectional study. PARTICIPANTS: Not applicable. METHODS: In this cross-sectional study, 23 websites publishing medical surgery training video content were queried using the keyword "Ahmed glaucoma valve implantation". MAIN OUTCOME MEASURES: The descriptive statistics of video parameters were noted, and the videos were assessed using established scoring systems-Sandvik, Health on the Net Foundation Code of Conduct (HON code), mDISCERN, and Global Quality Score (GQS) scores. Video Quality Score (VQS) was determined based on the 14 steps per the AGV implantation rubric. RESULTS: One hundred and nineteen videos were evaluated, and 35 were excluded. The total quality of all 84 videos according to their Sandvik, HON Code, GQS, DISCERN, and VQS scores was 11.79 ± 1.70 (excellent quality), 6.86 ± 0.75 (excellent quality), 3.97 ± 0.93 (good quality), 3.26 ± 0.66 (fair quality) and 11.45 ± 2.67 (good quality), respectively. No significant correlation was found between the descriptive parameters and video quality score. However, no significant correlation was found between the descriptive parameters and video quality score. CONCLUSIONS: The objective analysis showed that the video quality ranged from good to excellent. AGV implantation videos were sparse on exclusive ophthalmology surgical video portals. Therefore, more peer-reviewed videos following standardized rubric are needed on open-access surgical video platforms.


Asunto(s)
Glaucoma , Humanos , Estudios Transversales , Reproducibilidad de los Resultados , Escolaridad , Glaucoma/cirugía , Internet
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