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1.
Retina ; 44(9): 1565-1571, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39167578

RESUMEN

PURPOSE: To evaluate the long-term anatomic and visual outcomes in eyes with sickle cell retinopathy-related retinal detachments (RDs). METHODS: Patients who underwent surgery for sickle cell retinopathy-related RDs at the Wilmer Eye Institute or Wills Eye Hospital between 2008 and 2020 and followed for at least 6 months postoperatively were retrospectively reviewed. The primary outcome was the rate of single-surgery anatomic success and final reattachment. RESULTS: This study included 30 eyes from 28 patients (16 women and 12 men) with tractional RD (n = 13), rhegmatogenous RD (n = 1), and combined tractional RD/rhegmatogenous RD (n = 16). Mean age was 42.1 ± 15.1 years. The mean follow-up duration was 47.8 ± 34.1 months. Twenty-five (83.3%) eyes underwent pars plana vitrectomy and five (16.7%) eyes underwent pars plana vitrectomy with scleral buckling. Single-surgery anatomic success was achieved in 21 (70.0%) eyes at 6 months. Final reattachment was achieved in 28 (93.3%) eyes (22 eyes [73.3%] without tamponade). Recurrence of RDs was significantly associated with male gender (P = 0.041), absence of previous laser (P = 0.032), iatrogenic breaks (P = 0.035), retinectomy (P = 0.034), and silicone oil tamponade (P = 0.024). Overall, the logarithm of the minimum angle of resolution visual acuity improved from 1.53 ± 0.57 (Snellen equivalent, 20/678) to 1.15 ± 1.01 (20/283) at the final visit (P = 0.03); however, eyes with recurrent RD did not achieve significant visual improvement. CONCLUSION: Pars plana vitrectomy to repair sickle cell retinopathy-related RDs was effective in achieving anatomic success and improving vision in most eyes. Single-surgery anatomic success is critical for optimizing visual outcomes.


Asunto(s)
Anemia de Células Falciformes , Desprendimiento de Retina , Curvatura de la Esclerótica , Agudeza Visual , Vitrectomía , Humanos , Desprendimiento de Retina/cirugía , Desprendimiento de Retina/etiología , Desprendimiento de Retina/diagnóstico , Masculino , Femenino , Estudios Retrospectivos , Adulto , Agudeza Visual/fisiología , Vitrectomía/métodos , Anemia de Células Falciformes/complicaciones , Curvatura de la Esclerótica/métodos , Estudios de Seguimiento , Persona de Mediana Edad , Resultado del Tratamiento , Adulto Joven , Endotaponamiento/métodos
2.
Emerg Infect Dis ; 29(4): 761-770, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36918377

RESUMEN

SARS-CoV-2 infections among vaccinated nursing home residents increased after the Omicron variant emerged. Data on booster dose effectiveness in this population are limited. During July 2021-March 2022, nursing home outbreaks in 11 US jurisdictions involving >3 infections within 14 days among residents who had received at least the primary COVID-19 vaccine(s) were monitored. Among 2,188 nursing homes, 1,247 outbreaks were reported in the periods of Delta (n = 356, 29%), mixed Delta/Omicron (n = 354, 28%), and Omicron (n = 536, 43%) predominance. During the Omicron-predominant period, the risk for infection within 14 days of an outbreak start was lower among boosted residents than among residents who had received the primary vaccine series alone (risk ratio [RR] 0.25, 95% CI 0.19-0.33). Once infected, boosted residents were at lower risk for all-cause hospitalization (RR 0.48, 95% CI 0.40-0.49) and death (RR 0.45, 95% CI 0.34-0.59) than primary vaccine-only residents.


Asunto(s)
COVID-19 , Estados Unidos/epidemiología , Humanos , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19 , SARS-CoV-2 , Casas de Salud , Brotes de Enfermedades
3.
MMWR Morb Mortal Wkly Rep ; 71(4): 132-138, 2022 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-35085223

RESUMEN

Previous reports of COVID-19 case, hospitalization, and death rates by vaccination status† indicate that vaccine protection against infection, as well as serious COVID-19 illness for some groups, declined with the emergence of the B.1.617.2 (Delta) variant of SARS-CoV-2, the virus that causes COVID-19, and waning of vaccine-induced immunity (1-4). During August-November 2021, CDC recommended§ additional primary COVID-19 vaccine doses among immunocompromised persons and booster doses among persons aged ≥18 years (5). The SARS-CoV-2 B.1.1.529 (Omicron) variant emerged in the United States during December 2021 (6) and by December 25 accounted for 72% of sequenced lineages (7). To assess the impact of full vaccination with additional and booster doses (booster doses),¶ case and death rates and incidence rate ratios (IRRs) were estimated among unvaccinated and fully vaccinated adults by receipt of booster doses during pre-Delta (April-May 2021), Delta emergence (June 2021), Delta predominance (July-November 2021), and Omicron emergence (December 2021) periods in the United States. During 2021, averaged weekly, age-standardized case IRRs among unvaccinated persons compared with fully vaccinated persons decreased from 13.9 pre-Delta to 8.7 as Delta emerged, and to 5.1 during the period of Delta predominance. During October-November, unvaccinated persons had 13.9 and 53.2 times the risks for infection and COVID-19-associated death, respectively, compared with fully vaccinated persons who received booster doses, and 4.0 and 12.7 times the risks compared with fully vaccinated persons without booster doses. When the Omicron variant emerged during December 2021, case IRRs decreased to 4.9 for fully vaccinated persons with booster doses and 2.8 for those without booster doses, relative to October-November 2021. The highest impact of booster doses against infection and death compared with full vaccination without booster doses was recorded among persons aged 50-64 and ≥65 years. Eligible persons should stay up to date with COVID-19 vaccinations.


Asunto(s)
Vacunas contra la COVID-19/inmunología , COVID-19/epidemiología , COVID-19/mortalidad , COVID-19/prevención & control , Inmunización Secundaria , SARS-CoV-2/inmunología , Eficacia de las Vacunas , Adulto , Anciano , Humanos , Incidencia , Persona de Mediana Edad , Estados Unidos/epidemiología
4.
Curr Diab Rep ; 21(10): 40, 2021 09 08.
Artículo en Inglés | MEDLINE | ID: mdl-34495377

RESUMEN

PURPOSE OF REVIEW: Diabetic retinopathy (DR) is one of the leading causes of vision loss worldwide. Although screening and early treatment guidelines for DR have significantly reduced the disease burden, restrictions related to the COVID-19 pandemic have changed real-world practice patterns in the management of DR. This review summarizes evolving guidelines and outcomes of the treatment of DR in the setting of the pandemic. RECENT FINDINGS: Intravitreal injections for DR have decreased significantly globally during the pandemic, ranging from approximately 30 to nearly 100% reduction, compared to corresponding timepoints in 2019. Most studies on functional outcomes show a decrease in visual acuity on delayed follow-up. Changing practice patterns in the management of DR has led to fewer intravitreal injections and overall reduction in visual acuity on follow-up. As COVID variants emerge, it will be necessary to continue evaluating practice guidelines.


Asunto(s)
COVID-19 , Retinopatía Diabética , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/tratamiento farmacológico , Estudios de Seguimiento , Humanos , Pandemias , SARS-CoV-2 , Resultado del Tratamiento
5.
Proc Natl Acad Sci U S A ; 112(31): 9751-6, 2015 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-26195796

RESUMEN

Huntington's disease (HD) is a progressive neurodegenerative disease caused by a glutamine repeat expansion in mutant huntingtin (mHtt). Despite the known genetic cause of HD, the pathophysiology of this disease remains to be elucidated. Inositol polyphosphate multikinase (IPMK) is an enzyme that displays soluble inositol phosphate kinase activity, lipid kinase activity, and various noncatalytic interactions. We report a severe loss of IPMK in the striatum of HD patients and in several cellular and animal models of the disease. This depletion reflects mHtt-induced impairment of COUP-TF-interacting protein 2 (Ctip2), a striatal-enriched transcription factor for IPMK, as well as alterations in IPMK protein stability. IPMK overexpression reverses the metabolic activity deficit in a cell model of HD. IPMK depletion appears to mediate neural dysfunction, because intrastriatal delivery of IPMK abates the progression of motor abnormalities and rescues striatal pathology in transgenic murine models of HD.


Asunto(s)
Enfermedad de Huntington/enzimología , Enfermedad de Huntington/fisiopatología , Neuronas/patología , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Adulto , Anciano , Animales , Biocatálisis , Demografía , Dependovirus/metabolismo , Modelos Animales de Enfermedad , Estabilidad de Enzimas , Femenino , Humanos , Enfermedad de Huntington/genética , Enfermedad de Huntington/patología , Masculino , Ratones Transgénicos , Persona de Mediana Edad , Mitocondrias/metabolismo , Actividad Motora , Neostriado/enzimología , Neostriado/patología , Neostriado/fisiopatología , Neuronas/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Cambios Post Mortem , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas Represoras/metabolismo , Transducción de Señal , Análisis de Supervivencia , Transcripción Genética , Proteínas Supresoras de Tumor/metabolismo
6.
Proc Natl Acad Sci U S A ; 111(32): E3325-34, 2014 Aug 12.
Artículo en Inglés | MEDLINE | ID: mdl-25071185

RESUMEN

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that mediates adaptive responses to oxygen deprivation. In addition, the HIF-1α subunit has a nontranscriptional role as a negative regulator of DNA replication through effects on minichromosome maintenance helicase loading and activation. However, some cell types continue to replicate under hypoxic conditions. The mechanism by which these cells maintain proliferation in the presence of elevated HIF-1α levels is unclear. Here we report that HIF-1α physically and functionally interacts with cyclin-dependent kinase 1 (Cdk1) and Cdk2. Cdk1 activity blocks lysosomal degradation of HIF-1α and increases HIF-1α protein stability and transcriptional activity. By contrast, Cdk2 activity promotes lysosomal degradation of HIF-1α at the G1/S phase transition. Blocking lysosomal degradation by genetic or pharmacological means leads to HIF-1α-dependent cell-cycle arrest, demonstrating that lysosomal degradation of HIF-1α is an essential step for the maintenance of cell-cycle progression under hypoxic conditions.


Asunto(s)
Proteína Quinasa CDC2/metabolismo , Puntos de Control del Ciclo Celular/fisiología , Quinasa 2 Dependiente de la Ciclina/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Lisosomas/metabolismo , Animales , Línea Celular , Línea Celular Tumoral , Quinasa 2 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 2 Dependiente de la Ciclina/genética , Puntos de Control de la Fase G1 del Ciclo Celular/fisiología , Técnicas de Silenciamiento del Gen , Células HeLa , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Ratones , Complejo de la Endopetidasa Proteasomal/metabolismo , Estabilidad Proteica , Proteolisis
7.
Acta Neurochir Suppl ; 124: 159-164, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28120069

RESUMEN

INTRODUCTION: High-grade astrocytomas of the mesial temporal lobe may pose surgical challenges. Several approaches (trans-sylvian, subtemporal, and transcortical) have been designed to circumnavigate the critical neurovascular structures and white fiber tracts that surround this area. Considering the paucity of literature on the transcortical approach for these lesions, we describe our institutional experience with transcortical approaches to Grade III/IV astrocytomas in the mesial temporal lobe. METHODS: Between 1999 and 2009, 23 patients underwent surgery at the Johns Hopkins Medical Institutions for Grade III/IV astrocytomas involving the mesial temporal lobe (without involvement of the temporal neocortex). Clinical notes, operative records, and imaging were reviewed. RESULTS: Thirteen patients had tumors in the dominant hemisphere. All patients underwent surgery via a transcortical approach (14 via the inferior temporal gyrus and 9 via the middle temporal gyrus). Gross total resection was obtained in 92 % of the cohort. Neurological outcomes were: clinically significant stroke (2 patients), new visual deficits (2 patients), new speech deficit (1 patient); seizure control (53 %). CONCLUSIONS: In comparison to reported results in the literature for the transylvian and subtemporal approaches, the transcortical approach may provide the access necessary for a gross total resection with minimal neurological consequences. In our series of patients, there was no statistically significant difference in outcomes between the middle temporal gyrus versus the inferior temporal gyrus trajectories.


Asunto(s)
Astrocitoma/cirugía , Neoplasias Encefálicas/cirugía , Procedimientos Neuroquirúrgicos/métodos , Lóbulo Temporal/cirugía , Adulto , Anciano , Astrocitoma/complicaciones , Astrocitoma/patología , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Convulsiones/etiología , Trastornos del Habla/epidemiología , Accidente Cerebrovascular/epidemiología , Tretoquinol , Carga Tumoral , Trastornos de la Visión/epidemiología
8.
Proc Natl Acad Sci U S A ; 110(40): 16181-6, 2013 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-24043835

RESUMEN

Profound induction of immediate early genes (IEGs) by neural activation is a critical determinant for plasticity in the brain, but intervening molecular signals are not well characterized. We demonstrate that inositol polyphosphate multikinase (IPMK) acts noncatalytically as a transcriptional coactivator to mediate induction of numerous IEGs. IEG induction by electroconvulsive stimulation is virtually abolished in the brains of IPMK-deleted mice, which also display deficits in spatial memory. Neural activity stimulates binding of IPMK to the histone acetyltransferase CBP and enhances its recruitment to IEG promoters. Interestingly, IPMK regulation of CBP recruitment and IEG induction does not require its catalytic activities. Dominant-negative constructs, which prevent IPMK-CBP binding, substantially decrease IEG induction. As IPMK is ubiquitously expressed, its epigenetic regulation of IEGs may influence diverse nonneural and neural biologic processes.


Asunto(s)
Encéfalo/metabolismo , Epigénesis Genética/fisiología , Regulación de la Expresión Génica/fisiología , Genes Inmediatos-Precoces/fisiología , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Activación Transcripcional/fisiología , Análisis de Varianza , Animales , Proteína de Unión a CREB/metabolismo , Inmunoprecipitación de Cromatina , Regulación de la Expresión Génica/genética , Genes Inmediatos-Precoces/genética , Aprendizaje por Laberinto , Ratones , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Reconocimiento en Psicología/fisiología
9.
J Biol Chem ; 288(15): 10703-14, 2013 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-23457305

RESUMEN

Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric transcription factor that mediates adaptive responses to hypoxia. We demonstrate that lysosomal degradation of the HIF-1α subunit by chaperone-mediated autophagy (CMA) is a major regulator of HIF-1 activity. Pharmacological inhibitors of lysosomal degradation, such as bafilomycin and chloroquine, increased HIF-1α levels and HIF-1 activity, whereas activators of chaperone-mediated autophagy, including 6-aminonicotinamide and nutrient starvation, decreased HIF-1α levels and HIF-1 activity. In contrast, macroautophagy inhibitors did not increase HIF-1 activity. Transcription factor EB, a master regulator of lysosomal biogenesis, also negatively regulated HIF-1 activity. HIF-1α interacts with HSC70 and LAMP2A, which are core components of the CMA machinery. Overexpression of HSC70 or LAMP2A decreased HIF-1α protein levels, whereas knockdown had the opposite effect. Finally, hypoxia increased the transcription of genes involved in CMA and lysosomal biogenesis in cancer cells. Thus, pharmacological and genetic approaches identify CMA as a major regulator of HIF-1 activity and identify interplay between autophagy and the response to hypoxia.


Asunto(s)
Autofagia/fisiología , Proteínas del Choque Térmico HSC70/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Lisosomas/metabolismo , Proteolisis , Animales , Antirreumáticos/farmacología , Autofagia/efectos de los fármacos , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Hipoxia de la Célula/efectos de los fármacos , Hipoxia de la Célula/fisiología , Cloroquina/farmacología , Técnicas de Silenciamiento del Gen , Proteínas del Choque Térmico HSC70/genética , Células HeLa , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Lisosomas/genética , Ratones
10.
JAMA Ophthalmol ; 142(9): 845-854, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39115836

RESUMEN

Importance: Functional outcomes after repair of rhegmatogenous retinal detachments (RRDs) are highly dependent on baseline visual acuity and foveal status. Adverse social determinants of health (SDOH) can present barriers to timely presentation for repair and limit vision outcomes. Objective: To evaluate the association between neighborhood-level SDOH with baseline severity (visual acuity and fovea status) of RRD. Design, Setting, and Participants: This was a retrospective cohort study that included adult patients 18 years and older who underwent primary repair of uncomplicated RRD at the Wilmer Eye Institute from January 2008 to December 2018. Study data were analyzed from December 2023 to April 2024. Exposures: The census block group of patient home addresses were matched to multiple neighborhood-level SDOH including the Area Deprivation Index (ADI), per capita income, percentage of renters, percentage of rent burden, percentage of people using a food assistance program, percentage of uninsured individuals, mode of transportation to work, distance to the nearest transit stop, total road density, National Walkability Index, Index of Medical Underservice score, and aggregate cost of medical care. Main Outcomes and Measures: Odds of presenting with vision worse than 20/40 or fovea-involving RRD using multivariable logistic regression adjusting for age, sex, race and ethnicity, and insurance. Results: A total of 700 patients (mean [SD] age, 57.9 [12.4] years; 432 male [61.7%]) were included. Every decile increase in ADI, indicating more socioeconomic disadvantage, was associated with an increased odds of presenting with worse visual acuity and fovea-involving RRD (odds ratio [OR], 1.14; 95% CI, 1.04-1.24; P = .004 and OR, 1.13; 95% CI, 1.04-1.22; P = .005, respectively). Each $1000 increase in per capita income was associated with lower odds of presenting with worse vision (OR, 0.99; 95% CI, 0.98-0.99; P = .001). Every 1% increase in percentage of workers who drove to work was associated with an increased odds of presenting with worse vision and fovea-involving RRD (OR, 1.02; 95% CI, 1.01-1.03; P = .005 and OR, 1.01; 95% CI, 1.00-1.03; P = .04, respectively). Conclusions and Relevance: Results of this cohort study suggest that patients with a residence in neighborhoods with more socioeconomic deprivation or a higher percentage of workers who drove to work were more likely to present with more severe RRD even after accounting for multiple individual-level characteristics. These findings support consideration of public policy changes to address the barriers faced by patients residing in certain neighborhoods who seek prompt surgical intervention for RRD to reduce health disparities in RRD outcomes.


Asunto(s)
Desprendimiento de Retina , Determinantes Sociales de la Salud , Agudeza Visual , Humanos , Masculino , Estudios Retrospectivos , Desprendimiento de Retina/cirugía , Femenino , Persona de Mediana Edad , Agudeza Visual/fisiología , Adulto , Anciano , Características del Vecindario , Vitrectomía , Características de la Residencia
11.
Ophthalmol Retina ; 8(1): 42-48, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37660736

RESUMEN

PURPOSE: Classify the appearance and quantify the growth rate of chorioretinal atrophy in patients who received voretigene neparvovec-rzyl (VN) for RPE65-mediated retinal degeneration. DESIGN: Multicenter retrospective analysis. SUBJECTS: Patients who underwent subretinal VN injection at 5 institutions and demonstrated posterior-pole chorioretinal atrophy. METHODS: Ultrawidefield scanning laser ophthalmoscopy or color fundus photos were assessed before and after subretinal VN. Atrophy was defined as regions with ≥ 2 of the following: (1) partial or complete retinal pigment epithelial depigmentation; (2) round shape; (3) sharp margins; and (4) increased visibility of choroidal vessels. Atrophy was qualitatively classified into different subtypes. All atrophy was manually segmented. Linear mixed-effects models with random slopes and intercepts were fit using atrophy area and square root of atrophy area. MAIN OUTCOME MEASURES: Number of eyes with each atrophy pattern, and slopes of linear mixed-effects models. RESULTS: Twenty-seven eyes from 14 patients across 5 centers developed chorioretinal atrophy after subretinal VN. A mean of 5.8 ± 2.7 images per eye obtained over 2.2 ± 0.8 years were reviewed, and atrophy was categorized into touchdown (14 eyes), nummular (15 eyes), and perifoveal (12 eyes) subtypes. Fifteen eyes demonstrated > 1 type of atrophy. Thirteen of 14 patients demonstrated bilateral atrophy. The slopes of the mixed-effects models of atrophy area and square root of atrophy area (estimate ± standard error) were 1.7 ± 1.3 mm2/year and 0.6 ± 0.2 mm/year for touchdown atrophy, 5.5 ± 1.3 mm2/year and 1.2 ± 0.2 mm/year for nummular atrophy, and 16.7 ± 1.8 mm2/year and 2.3 ± 0.2 mm/year for perifoveal atrophy. The slopes for each type of atrophy were significantly different in the square root of atrophy model, which best fit the data (P < 0.05). CONCLUSIONS: Chorioretinal atrophy after subretinal VN for RPE65-mediated retinal degeneration developed according to a touchdown, nummular, and/or perifoveal pattern. Perifoveal atrophy grew the most rapidly, while touchdown atrophy grew the least rapidly. Understanding the causes of these findings, which are present in a minority of patients, merits further investigation. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.


Asunto(s)
Enfermedades de la Coroides , Degeneración Retiniana , Humanos , Degeneración Retiniana/diagnóstico , Degeneración Retiniana/genética , Estudios Retrospectivos , Atrofia
12.
J Neurosci ; 32(46): 16503-9, 2012 Nov 14.
Artículo en Inglés | MEDLINE | ID: mdl-23152632

RESUMEN

Parkinson's disease (PD) is a progressive neurodegenerative disease caused by the interaction of genetic and environmental factors. However, the etiology of PD remains largely unknown. Macroautophagy is known to play an essential role in the degradation of abnormal proteins and organelles. Furthermore, the loss of autophagy-related (Atg) genes results in neurodegeneration and abnormal protein accumulation. Since these are also pathologic features of Parkinson's disease, the conditional impairment of autophagy may lead to improved animal models for the study of PD. Using transgenic mice expressing Cre recombinase under the control of either the dopamine transporter or the engrailed-1 promoters, we generated mice with the conditional deletion of Atg7 in the dopamine neurons of the substantia nigra pars compacta, other regions of the midbrain, and also the hindbrain. This conditional impairment of autophagy results in the age-related loss of dopaminergic neurons and corresponding loss of striatal dopamine, the accumulation of low-molecular-weight α-synuclein, and the presence of ubiquitinated protein aggregates, recapitulating many of the pathologic features of PD. These conditional knock-out animals provide insight into the process of autophagy in Parkinson's disease pathology.


Asunto(s)
Autofagia/fisiología , Enfermedad de Parkinson/patología , Animales , Proteína 7 Relacionada con la Autofagia , Western Blotting , Recuento de Células , Cromatografía Líquida de Alta Presión , Modelos Animales de Enfermedad , Dopamina/metabolismo , Neuronas Dopaminérgicas/fisiología , Complejo Dinactina , Electroquímica , Eliminación de Gen , Inmunohistoquímica , Ratones , Ratones Noqueados , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Neostriado/metabolismo , Neurotransmisores/metabolismo , Enfermedad de Parkinson/metabolismo , Poliubiquitina/metabolismo , Ubiquitina/metabolismo , alfa-Sinucleína/metabolismo
13.
Semin Ophthalmol ; 38(2): 151-157, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36448810

RESUMEN

PURPOSE: To provide an overview of the impact of retinopathy of prematurity (ROP), and the challenges in the screening, diagnosis, and treatment of ROP worldwide. METHODS: A comprehensive search was conducted using the PubMed database from January 2011 to October 2021 using the following keywords: retinopathy of prematurity, laser, and anti-vascular endothelial growth factor (VEGF). Data on patient characteristics, ROP treatment type, and recurrence rates were collected. The countries included in these studies were classified based on 2021-2022 World Bank definitions of high, upper-middle, lower-middle, and low-income groups. Moreover, a search for surgical outcomes for ROP and screening algorithms and artificial intelligence for ROP was conducted. RESULTS: Thirty-nine studies met the inclusion criteria. ROP treatment and outcomes showed a trend towards intravitreal anti-VEGF injections as the initial treatment for ROP globally and the treatment of recurrent ROP in high-income countries. However, laser remains the treatment of choice for ROP recurrence in middle-income countries. Surgical outcomes for ROP stage 4A, 4B and 5 are similar worldwide. The incidence of ROP and ROP-related visual impairment continue to increase globally. Although telemedicine and artificial intelligence offer potential solutions to ROP screening in resource-limited areas, the current models require further optimization to reflect the global diversity of ROP patients. CONCLUSION: ROP screening and treatment paradigms vary widely based on country income group due to disparities in resources, limited access to care, and lack of universal guidelines.


Asunto(s)
Retinopatía de la Prematuridad , Recién Nacido , Humanos , Retinopatía de la Prematuridad/diagnóstico , Retinopatía de la Prematuridad/epidemiología , Retinopatía de la Prematuridad/cirugía , Inhibidores de la Angiogénesis , Factor A de Crecimiento Endotelial Vascular , Inteligencia Artificial , Coagulación con Láser , Inyecciones Intravítreas , Edad Gestacional
14.
Ophthalmol Retina ; 2023 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-38036083

RESUMEN

PURPOSE: To investigate predictors of the development and resolution of cystoid macular edema (CME) after rhegmatogenous retinal detachment (RRD) repair. DESIGN: Retrospective cross sectional study. SUBJECTS: Patients who underwent primary repair of uncomplicated RRD. METHODS: Demographics, ophthalmic history, visual acuity, RRD features, time to development/resolution of CME, OCT characteristics of CME/epiretinal membrane (ERM), type of surgery, and treatments were collected. Logistic regressions were used to identify predictors of CME development and resolution. MAIN OUTCOME MEASURES: Predictors of CME development and resolution. RESULTS: A total of 708 eyes were included, of which 55 (7.8%) developed CME. Factors associated with an increased risk of CME development included total number of retinal detachment surgeries (odds ratio [OR] 1.66 [1.24-2.23], P < 0.001), prior intraocular surgery (OR 4.43 [1.19-16.51], P = 0.03), and presence of ERM after surgery (OR 4.49 [2.30-8.74], P < 0.001). Patients undergoing pars plana vitrectomy (PPV) were more likely to develop CME compared with patients undergoing scleral buckling (SB; OR 3.09 [1.18-8.10], P = 0.02). A longer average time to CME detection was associated with lower CME resolution (OR 0.94 [0.89-0.998], P = 0.04). In patients who developed an ERM postsurgically, those who developed CME after ERM had a lower rate of resolution compared with those who developed CME before ERM (P = 0.03). CONCLUSIONS: Cystoid macular edema may be more likely to develop in patients undergoing PPV than SB, those who underwent more surgeries for RRD repair, those who had prior intraocular surgery, or those who developed an ERM after RRD repair. Resolution of CME may be affected by the time to detection of CME and ERM development. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

15.
Eye (Lond) ; 37(4): 684-691, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-35338355

RESUMEN

OBJECTIVE: To investigate practice patterns and clinical outcomes in the repair of uncomplicated rhegmatogenous retinal detachments (RRD) in a real-world setting over a 10-year period. METHODS: We compared preferences for scleral buckling (SB), pars plana vitrectomy (PPV), PPV/SB, or pneumatic retinopexy (PR) over time, and examined the 1-year single surgery anatomic success (SSAS) and best-corrected visual acuity (BCVA) at a tertiary academic institution from 2008-2018. RESULTS: Eight hundred eight eyes had RRD repair between 2008-2011 (n = 240), 2012-2014 (n = 271), and 2015-2017 (n = 297). Compared to 2008-2011, PPV was preferred over SB in 2012-2014 (OR: 2.93; 95% CI: 1.86-4.63) and 2015-2017 (OR: 5.94; 95% CI: 3.76-9.38), and over PPV/SB in 2012-2014 (OR: 2.74; 95% CI: 1.65-4.56) and 2015-2017 (OR: 3.16; 95% CI: 31.96-5.12). PR was uncommonly utilized (<10%). Younger surgeons (graduating 2010-2017) favored PPV over SB when compared to older surgeons [graduating 1984-2000 (OR: 1.77; 95% CI: 1.18-2.65) and 2001-2009 (OR 1.73; 95% CI: 1.14-2.65)], but similarly selected PPV vs. PPV/SB as their older counterparts (p > 0.05). Compared to PPV, SSAS was higher with SB (OR: 1.53; 95% CI: 1.03-2.26) and PPV/SB (OR: 2.55; 95% CI: 1.56-4.17). One-year BCVA was markedly improved compared to baseline only for eyes that achieved SSAS (p < 0.001). CONCLUSIONS: Over the past 10 years, PPV has become the favored approach to repair uncomplicated RRD and this appears to be driven by younger surgeons' preferences. Given the superior long-term SSAS in SB and PPV/SB as compared to PPV, SB and PPV/SB should be more frequently considered when determining the appropriate repair strategy for uncomplicated RRD.


Asunto(s)
Desprendimiento de Retina , Humanos , Desprendimiento de Retina/cirugía , Desprendimiento de Retina/etiología , Resultado del Tratamiento , Agudeza Visual , Estudios Retrospectivos , Curvatura de la Esclerótica/efectos adversos , Vitrectomía/efectos adversos
16.
Cornea ; 42(7): 805-814, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-36441843

RESUMEN

PURPOSE: The purpose of this study was to assess the role of combined surgical treatment of therapeutic penetrating keratoplasty and pars plana vitrectomy in the anatomical and functional outcome of infectious keratitis endophthalmitis. METHODS: This study reviewed the medical records of 4 participating centers in the United States and Mexico. This study included patients with a clinical diagnosis of infectious keratitis endophthalmitis who had been treated with an early therapeutic penetrating keratoplasty and pars plana vitrectomy as the main treatment for endophthalmitis. From each medical record, the study retrieved demographic data, relevant medical and drug history, baseline clinical manifestation of endophthalmitis, best-corrected visual acuity, and the need for enucleation/evisceration for the control of the infection or any other reason through the follow-up. RESULTS: The study included 48 patients (50.15 ± 20.6 years). The mean follow-up time was 13 ± 0.5 months. The mean best-corrected visual acuity at baseline was 2.1 ± 0.25 logarithm of the minimum angle of resolution. At month 12 was 2.09 ± 0.61 logarithm of the minimum angle of resolution ( P = 0.9). The overall prevalence of enucleation/evisceration was 8.3% (95% confidence interval: 2.32%-19.98%). The prevalence of a vision of no-light perception was 20.8% (95% confidence interval: 2.32%-19.98%). CONCLUSIONS: Combined surgery for severe cases of infectious keratitis endophthalmitis eradicates the infection in most cases, while significantly improving the overall outcomes.


Asunto(s)
Endoftalmitis , Queratitis , Humanos , Vitrectomía/métodos , Queratoplastia Penetrante/métodos , México/epidemiología , Resultado del Tratamiento , Endoftalmitis/diagnóstico , Endoftalmitis/cirugía , Endoftalmitis/tratamiento farmacológico , Queratitis/cirugía , Estudios Retrospectivos
18.
Infect Control Hosp Epidemiol ; 44(6): 1005-1009, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36645205

RESUMEN

Among nursing home outbreaks of coronavirus disease 2019 (COVID-19) with ≥3 breakthrough infections when the predominant severe acute respiratory coronavirus virus 2 (SARS-CoV-2) variant circulating was the SARS-CoV-2 δ (delta) variant, fully vaccinated residents were 28% less likely to be infected than were unvaccinated residents. Once infected, they had approximately half the risk for all-cause hospitalization and all-cause death compared with unvaccinated infected residents.


Asunto(s)
COVID-19 , Virosis , Humanos , SARS-CoV-2 , Vacunas contra la COVID-19 , COVID-19/epidemiología , COVID-19/prevención & control , Casas de Salud , Brotes de Enfermedades/prevención & control
19.
PLoS One ; 18(9): e0291678, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37729332

RESUMEN

BACKGROUND: SARS-CoV-2 Omicron variants have the potential to impact vaccine effectiveness and duration of vaccine-derived immunity. We analyzed U.S. multi-jurisdictional COVID-19 vaccine breakthrough surveillance data to examine potential waning of protection against SARS-CoV-2 infection for the Pfizer-BioNTech (BNT162b) primary vaccination series by age. METHODS: Weekly numbers of SARS-CoV-2 infections during January 16, 2022-May 28, 2022 were analyzed by age group from 22 U.S. jurisdictions that routinely linked COVID-19 case surveillance and immunization data. A life table approach incorporating line-listed and aggregated COVID-19 case datasets with vaccine administration and U.S. Census data was used to estimate hazard rates of SARS-CoV-2 infections, hazard rate ratios (HRR) and percent reductions in hazard rate comparing unvaccinated people to people vaccinated with a Pfizer-BioNTech primary series only, by age group and time since vaccination. RESULTS: The percent reduction in hazard rates for persons 2 weeks after vaccination with a Pfizer-BioNTech primary series compared with unvaccinated persons was lowest among children aged 5-11 years at 35.5% (95% CI: 33.3%, 37.6%) compared to the older age groups, which ranged from 68.7%-89.6%. By 19 weeks after vaccination, all age groups showed decreases in the percent reduction in the hazard rates compared with unvaccinated people; with the largest declines observed among those aged 5-11 and 12-17 years and more modest declines observed among those 18 years and older. CONCLUSIONS: The decline in vaccine protection against SARS-CoV-2 infection observed in this study is consistent with other studies and demonstrates that national case surveillance data were useful for assessing early signals in age-specific waning of vaccine protection during the initial period of SARS-CoV-2 Omicron variant predominance. The potential for waning immunity during the Omicron period emphasizes the importance of continued monitoring and consideration of optimal timing and provision of booster doses in the future.


Asunto(s)
COVID-19 , Vacunas , Niño , Humanos , Anciano , Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19/epidemiología , COVID-19/prevención & control , Tablas de Vida , SARS-CoV-2
20.
J Ophthalmic Inflamm Infect ; 12(1): 26, 2022 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-35916989

RESUMEN

While socioeconomic disparities impact clinical care and patient outcomes, their impact on the anatomic and visual outcomes of retinal detachment in patients with viral retinitis is unstudied. This case series included 18 eyes in 18 patients from a single academic institution between January 1, 2008 and December 31, 2018. Patient characteristics including age, sex, race, ethnicity, insurance, immunosuppression, viral retinitis, retinal detachment, retinal detachment repair, visual and anatomic outcomes, missed appointments, and Area Deprivation Index [ADI] were collected. The low-ADI group, indicating less socioeconomic disadvantage, was comprised of twelve patients with national ADIs less than 38, and the high-ADI group of six patients with national ADIs greater than 38. High-ADI patients tended to be younger (average age 38.0 versus 51.3; P = 0.06), of female sex (P = 0.03), and had more missed appointments (median 11.0 vs 0; P = 0.002). A similar number of patients in both the high-ADI and low-ADI groups underwent pars plana vitrectomy alone or pars plana vitrectomy with scleral buckle. Visual acuity was similar in the high-ADI group than in the low-ADI group at baseline, but worse at the final follow-up visit (P = 0.004). Post-operative and final visit ocular hypotony were more common in the high-ADI group (P = 0.02). In our series, socioeconomic disadvantage negatively affects the visual outcomes in patients with viral retinitis associated-retinal detachments. These factors should be considered by ophthalmologists when treating these patients.

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