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BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of vision loss. Photobiomodulation (PBM) offers a controversial approach for managing dry AMD, aiming to halt or reverse progression through mitochondrial activity modulation. However, the efficacy and clinical relevance of PBM as a potential approach for managing dry AMD remain debated. METHODS: We systematically searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) comparing PBM versus a sham in patients with dry AMD. We performed trial sequential analysis (TSA) and minimal clinically important difference (MCID) calculations to assess statistical and clinical significance applying a random-effects model with 95% confidence intervals (CI). RESULTS: We included three RCTs comprising 247 eyes. The pooled analysis showed that PBM significant improved BCVA (MD 1.76 letters; 95% CI: 0.04 to 3.48) and drusen volume (MD -0.12 mm³; 95% CI: -0.22 to -0.02) as compared with a sham control. However, the TSA indicated that the current sample sizes were insufficient for reliable conclusions. No significant differences were observed in GA area. The MCID analysis suggested that the statistically significant results did not translate into clinically significant benefits. In the quality assessment, all studies were deemed to have a high risk of bias. CONCLUSION: This meta-analysis points limitations in the current evidence base for PBM in dry AMD treatment, with issues around small sample sizes. Statistically significant improvements do not translate into clinical benefits. The research underscores need for larger RCTs to validate PBM's therapeutic potential for dry AMD.
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Los leiomiomas son tumores mesenquimatosos benignos que se presentan como la neoplasia uterina más común en mujeres en edad reproductiva. Según su crecimiento, se puede ver comprometido su aporte sanguíneo, ocurriendo cambios degenerativos por la carencia de oxígeno, lo cual le confiere un aspecto atípico que puede generar confusión con el diagnostico. Se describe caso de paciente de 47 años de edad, quien consulta por aumento progresivo de volumen de circunferencia abdominal de 7 meses de evolución, referida a la consulta de ginecología oncológica por gran masa tumoral retrouterina de probable origen ovárico con elevado riesgo de malignidad. Luego de realizar estudios preoperatorios es llevada a quirófano, obteniéndose como diagnóstico definitivo, leiomioma con degeneración hialina e hidrópica focal. Los leiomiomas con cambios degenerativos pueden simular tumores malignos de ovario, por lo cual deben ser considerados como un diagnóstico diferencial antes de intervenciones quirúrgicas por tumores abdominopélvicos de gran tamaño(AU)
Leiomyomas are benign mesenchymal tumors that occur as the most common uterine neoplasm in women of reproductive age. Depending on its growth, its blood supply may be compromised, causing degenerative changes due to lack of oxygen, which gives it an atypical appearance that may cause confusion with the diagnosis. The case of a 47-year-old patient is described, who consults for a progressive increase in the volume of abdominal circumference of 7 months of evolution, referred to the gynecology oncology consultation due to a large retrouterine tumor mass of probable ovarian origin with a high risk of malignancy. After performing preoperative studies, she was taken to the operating room, obtaining as a definitive diagnosis, leiomyoma with hyaline and focal hydropic degeneration. Leiomyomas with degenerative changes can simulate malignant ovarian tumors, which is why they should be considered as a differential diagnosis before surgical interventions for large abdominopelvic tumors(AU)
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Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias Ovarianas , Fibroma , Laparotomia , Leiomioma , Cirurgia Geral , Ultrassom , Diagnóstico por ImagemRESUMO
INTRODUCTION: To evaluate the relationship between initial displacement in proximal humeral fractures and fatty degeneration of the rotator cuff measured by CT according to the Goutallier classification. MATERIAL AND METHODS: This cross-sectional observational study evaluated patients with proximal humeral fractures over a six-month period. The study included patients ≥ 18 years old with complete radiological views (anteroposterior, lateral, and Grashey) and a CT scan of the affected shoulder; previous fracture or ipsilateral shoulder surgery were excluded. Neer's classification system and Goutallier stages were used to evaluate the patients. Demographic data were collected and, two groups were analysed according to age (≤ 50 years and > 50 years). RESULTS: Sixty-two patients were included (m = 36, f = 26, ratio 1.3:1); seven patients were excluded. Male patients (36, 58.1%), patients older than 50 years (33, 53.2%) and a low-energy injury mechanism (36, 58.1%) were the most frequent cases. According to the Neer system, the most common proximal humerus fracture was fracture-dislocation in 17 (27.4%) cases. The most common stage in Goutallier's classification was I (some fatty streaks) in 22 (35.4%) cases. Younger patients (≤ 50 years) had more displaced fractures with low fatty degeneration (p = < 0.001) than older patients (> 50 years), who had minimally displaced fractures with greater fatty degeneration (p = 0.567). CONCLUSIONS: High-energy mechanisms are associated with younger patients and a more displaced fracture according to the Neer classification. Older patients had a more advanced Goutallier stage and lesser displaced fracture. We should consider a more aggressive approach in the treatment of non-displaced fractures in elderly patients, less conservative and more surgical management, to obtain a better clinical evolution after the treatment of these kinds of fractures. LEVEL OF EVIDENCE: IV.
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Manguito Rotador , Fraturas do Ombro , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Fraturas do Ombro/diagnóstico por imagem , Fraturas do Ombro/classificação , Fraturas do Ombro/complicações , Estudos Transversais , Idoso , Adulto , Manguito Rotador/diagnóstico por imagem , Manguito Rotador/patologia , Tomografia Computadorizada por Raios X , Tecido Adiposo/diagnóstico por imagem , Tecido Adiposo/patologia , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Prevalence of bioprosthetic valve degeneration (BVD) is rising as the use of bioprosthetic aortic valves increases. Detecting early signs of BVD remains a challenge, with conventional imaging methods often failing to identify early deterioration stages. 18F-fuoride positron emission tomography (PET-CT) is an emerging technique that offers promising prospects to detect subclinical BVD. This study aimed to compare early PET parameters of fluoride uptake with echocardiographic hemodynamic parameters and compare outcomes according to anticoagulation in patients who received bioprosthetic valves. METHODS: This is a sub-study of the ANTIPRO clinical trial, which involved patients undergoing surgical aortic valve replacement (SAVR) with a porcine bioprosthesis and randomized them into anticoagulated and non-anticoagulated groups. Hemodynamic changes were assessed by transthoracic echocardiography (TTE), while 18F-fluoride PET-CT quantified fluoride uptake and divided the patients in two groups: high-uptake and low-uptake. Mean and maximum gradients by TTE at three years were compared between the two uptake groups. Fluoride uptake was also compared between the anticoagulated and control groups. RESULTS: We found no significant differences in transprosthetic gradients between high-uptake(21.4 ± 8.6 mmHg) and low-uptake(17.3 ± 11.2 mmHg.p = 0.244) PET-defined groups in this specific timeframe. Notably, anticoagulated patients exhibited significantly risk of higher fluoride uptake(OR = 4.34;95%CI:1.04-18.21.p = 0.045). CONCLUSIONS: No association was found between fluoride uptake and hemodynamic evaluation. Anticoagulation was associated with higher fluoride uptake. These findings highlight the emerging role of PET-CT in studying bioprosthetic aortic valves and emphasize the need for extended follow-up to evaluate the impact of anticoagulation on valve degeneration.
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Anticoagulantes , Valva Aórtica , Bioprótese , Próteses Valvulares Cardíacas , Varfarina , Bioprótese/efeitos adversos , Humanos , Feminino , Masculino , Próteses Valvulares Cardíacas/efeitos adversos , Anticoagulantes/administração & dosagem , Idoso , Varfarina/administração & dosagem , Varfarina/farmacocinética , Varfarina/uso terapêutico , Valva Aórtica/cirurgia , Valva Aórtica/diagnóstico por imagem , Radioisótopos de Flúor , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Pessoa de Meia-Idade , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico por imagem , Seguimentos , Falha de Prótese , Tomografia por Emissão de Pósitrons/métodosRESUMO
Temporomandibular disorders (TMD) can have multiple etiologies, including oromandibular dystonia (OMD). However, in a few cases, the OMD can evolve from cervical dystonia (CD), leading to severe bone degeneration. The purpose of this case report of a 64-year-old woman presenting to the Outpatient Neurology Clinic of the Federal University of Bahia is to illustrate the development of oromandibular dystonia with temporomandibular joint (TMJ) dysfunction after 10 years of cervical dystonia. Clinical examination showed bone degeneration of the mandibular ramus and right TMJ click, a prevalent sound in patients with temporomandibular disorders when they open their mouths or chew. After onabotulinum toxin type A injections in the right lateral pterygoid muscle, the patient improved in swallowing and pain. This case highlights the importance of close follow-up of cervical dystonia patients to identify new dystonic muscles. In our patient, lateral pterygoid muscle involvement was followed by several comorbidities, such as dysphagia and jawbone abnormalities.
Os distúrbios temporomandibulares (DTM) podem ter múltiplas etiologias, incluindo a distonia oromandibular (DO). No entanto, em raros casos, a DO pode evoluir a partir da distonia cervical (DC) e raramente pode levar a degeneração óssea. O objetivo deste relato de caso de uma mulher de 64 anos atendida no Ambulatório de Neurologia da universidade Federal da Bahia é ilustrar o desenvolvimento de distonia oromandibular com disfunção da articulação temporomandibular (ATM) após 10 anos de distonia cervical. O exame clínico mostrou degeneração óssea do ramo mandibular e clique na ATM direita, um som prevalente em pacientes com distúrbios temporomandibulares quando abrem a boca ou mastigam. Após injeções de toxina botulínica tipo A no músculo pterigoideo lateral direito, a paciente apresentou melhora na deglutição e na dor. Este caso destaca a importância do acompanhamento próximo de pacientes com distonia cervical para identificar novos músculos distônicos. Em nossa paciente, o envolvimento do músculo pterigoide lateral foi seguido por várias comorbidades, como disfagia e anormalidades ósseas da mandíbula.
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Corticobasal syndrome (CBS) is a rare cause of dementia and comprises varied combinations of subcortical signs (akinetic-rigid parkinsonism, dystonia, or myoclonus) with cortical signs (apraxia, alien hand or cortical sensory deficit), usually asymmetric. We aimed to report and compare the clinical and neuroimaging presentation of two patients diagnosed with CBS. While case 1 had severe non-fluent aphasia associated with mild apraxia and limb rigidity, case 2 had a more posterior cognitive impairment, with a different language pattern associated with marked visuospatial errors and hemineglect. FDG PET played a significant role in diagnosis, suggesting, in the first case, corticobasal degeneration and, in the second, Alzheimer's disease pattern. CBS has been widely studied with the advent of new in vivo methods such as brain FDG PET. Studies that deepen the phenotypic and biomarker heterogeneity of CBS will be of great importance for better classification, prognosis, and treatment of the condition.
A síndrome corticobasal (SCB) é uma causa rara de demência e compreende combinações variadas de sinais subcorticais (parkinsonismo acinético-rígido, distonia ou mioclonias) com sinais corticais (apraxia, mão alienígena ou déficit sensorial cortical), geralmente assimétricos. Nosso objetivo foi relatar e comparar as apresentações clínica e de neuroimagem de dois pacientes com diagnóstico de SCB. Enquanto o caso 1 apresentava afasia grave não fluente associada a apraxia leve e rigidez de membros, o caso 2 exibia comprometimento cognitivo mais posterior, com padrão de linguagem distinto, erros visuoespaciais e heminegligência. O FDG PET teve papel significativo no diagnóstico, sugerindo, no primeiro caso, degeneração corticobasal e, no segundo, padrão Alzheimer. A SCB tem sido amplamente estudada com o advento de novos métodos in vivo, como o FDG PET cerebral. Estudos que aprofundem a heterogeneidade fenotípica e de biomarcadores da SCB serão de grande importância para melhor classificação, prognóstico e tratamento da doença.
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Objective: To compare effectiveness of Dynesys and hybrid system in treating patients with multi-segmental lumbar degenerative disease (LDD). Methods: Patients involved in this retrospective study were divided into Dynesys (n = 22) and Hybrid (n = 13) groups. Clinical outcomes were evaluated using Oswestry Disability Index (ODI), and Visual Analogue Scale (VAS). Radiologic evaluations included X-ray, MRI, and CT. Furthermore, different complications were analyzed. Results: At the last follow-up, ODI and VAS of each group were improved (p < 0.05), and the range of motion (ROM) of operating segments decreased. However, Dynesys group preserved a larger extent of ROM at the final follow-up (p < 0.05). ROM of the upper adjacent segment was increased in both groups (p < 0.05), while the disc heights were decreased at the final follow-up (p < 0.05). Besides, Dynesys group had a more obvious decrease in the disc height of dynamic segments (p < 0.05). No significant difference existed in complications between both groups (p > 0. 05). Conclusion: In our study, similar satisfactory results were obtained in both groups. Both surgical procedures can be employed as effective treatments for middle-aged and physically active patients with multi-segmental LDD. Level of Evidence III; Retrospective Comparative Study.
Objetivo: Comparar a eficácia do Dynesys e do sistema híbrido no tratamento de pacientes com doença degenerativa lombar multissegmentar (DLD). Métodos: Os pacientes envolvidos neste estudo retrospectivo foram divididos em grupos Dynesys (n = 22) e Híbrido (n = 13). Os desfechos clínicos foram avaliados por meio do Oswestry Disability Index (ODI) e da Escala Visual Analógica (EVA). As avaliações radiológicas incluíram radiografia, ressonância nuclear magnética (RNM) e tomografia computadorizada. Ademais, diferentes complicações foram analisadas. Resultados: No acompanhamento final, o ODI e a EVA de todos os grupos melhoraram (p < 0,05), e houve diminuição da amplitude de movimento (ADM) dos segmentos operacionais. No entanto, o grupo Dynesys preservou uma maior extensão da ADM no acompanhamento final (p < 0,05). A ADM do segmento superior adjacente foi ampliada em ambos os grupos (p < 0,05), enquanto as alturas dos discos foram reduzidas no acompanhamento final (p < 0,05). No entanto, o grupo Dynesys apresentou uma redução mais evidente na altura do disco dos segmentos dinâmicos (p < 0,05). Não houve diferença significativa nas complicações entre esses dois grupos (p > 0,05). Conclusão: Neste estudo, resultados satisfatórios semelhantes foram obtidos em ambos os grupos. Ambos os procedimentos cirúrgicos podem ser empregados como tratamentos eficazes para pacientes de meia-idade e fisicamente ativos com LDD multissegmentar. Nível de Evidência III; Estudo Retrospectivo Comparativo.
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It is widely acknowledged that aging, mitochondrial dysfunction, and cellular phenotypic abnormalities are intricately associated with the degeneration of bone and cartilage. Consequently, gaining a comprehensive understanding of the regulatory patterns governing mitochondrial function and its underlying mechanisms holds promise for mitigating the progression of osteoarthritis, intervertebral disc degeneration, and osteoporosis. Mitochondrial hormesis, referred to as mitohormesis, represents a cellular adaptive stress response mechanism wherein mitochondria restore homeostasis and augment resistance capabilities against stimuli by generating reactive oxygen species (ROS), orchestrating unfolded protein reactions (UPRmt), inducing mitochondrial-derived peptides (MDP), instigating mitochondrial dynamic changes, and activating mitophagy, all prompted by low doses of stressors. The varying nature, intensity, and duration of stimulus sources elicit divergent degrees of mitochondrial stress responses, subsequently activating one or more signaling pathways to initiate mitohormesis. This review focuses specifically on the effector molecules and regulatory networks associated with mitohormesis, while also scrutinizing extant mechanisms of mitochondrial dysfunction contributing to bone and cartilage degeneration through oxidative stress damage. Additionally, it underscores the potential of mechanical stimulation, intermittent dietary restrictions, hypoxic preconditioning, and low-dose toxic compounds to trigger mitohormesis, thereby alleviating bone and cartilage degeneration.
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Hormese , Mitocôndrias , Estresse Oxidativo , Humanos , Hormese/fisiologia , Mitocôndrias/fisiologia , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Animais , Osteoartrite/terapia , Osteoartrite/fisiopatologia , Transdução de Sinais/fisiologiaRESUMO
We reported thirteen cases of bilateral stringhalt associated with Hypochaeris radicata that occurred in horses in Uruguay during a severe drought in the summer of 2023. All horses were affected chronically and progressively by bilateral hyperflexion of hindlimbs. In two severely affected horses, the main histological lesions included neuronal chromatolysis and axonal spheroids in the ventral gray horn in the lumbar and sacral spinal cord and axonal degeneration and digestion chambers in ventral roots fibers and long peripheral nerves. We suggest that in addition to injuries to peripheral nerves, lesions in the spinal cord play an important role in the clinical signs of stringhalt in horses.
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Doenças dos Cavalos , Animais , Cavalos , Uruguai , Medula Espinal/patologia , Masculino , FemininoRESUMO
Non-exudative age-related macular degeneration (NE-AMD) is the leading blindness cause in the elderly. Clinical and experimental evidence supports that early alterations in macular retinal pigment epithelium (RPE) mitochondria play a key role in NE-AMD-induced damage. Mitochondrial dynamics (biogenesis, fusion, fission, and mitophagy), which is under the central control of AMP-activated kinase (AMPK), in turn, determines mitochondrial quality. We have developed a NE-AMD model in C57BL/6J mice induced by unilateral superior cervical ganglionectomy (SCGx), which progressively reproduces the disease hallmarks circumscribed to the temporal region of the RPE/outer retina that exhibits several characteristics of the human macula. In this work we have studied RPE mitochondrial structure, dynamics, function, and AMPK role on these parameters' regulation at the nasal and temporal RPE from control eyes and at an early stage of experimental NE-AMD (i.e., 4 weeks post-SCGx). Although RPE mitochondrial mass was preserved, their function, which was higher at the temporal than at the nasal RPE in control eyes, was significantly decreased at 4 weeks post-SCGx at the same region. Mitochondria were bigger, more elongated, and with denser cristae at the temporal RPE from control eyes. Exclusively at the temporal RPE, SCGx severely affected mitochondrial morphology and dynamics, together with the levels of phosphorylated AMPK (p-AMPK). AMPK activation with metformin restored RPE p-AMPK levels, and mitochondrial dynamics, structure, and function at 4 weeks post-SCGx, as well as visual function and RPE/outer retina structure at 10 weeks post-SCGx. These results demonstrate a key role of the temporal RPE mitochondrial homeostasis as an early target for NE-AMD-induced damage, and that pharmacological AMPK activation could preserve mitochondrial morphology, dynamics, and function, and, consequently, avoid the functional and structural damage induced by NE-AMD.
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Proteínas Quinases Ativadas por AMP , Modelos Animais de Doenças , Degeneração Macular , Camundongos Endogâmicos C57BL , Mitocôndrias , Dinâmica Mitocondrial , Epitélio Pigmentado da Retina , Animais , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Camundongos , Degeneração Macular/patologia , Degeneração Macular/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Proteínas Quinases Ativadas por AMP/metabolismo , Humanos , Metformina/farmacologiaRESUMO
Background: The wing-beating tremor, characteristic of Wilson's disease (WD), is a disabling symptom that can be resistant to anti-copper and anti-tremor medications. Phenomenology Shown: This video illustrates severe bilateral wing-beating tremor, moderate head and lower limb tremors, mild cervical dystonia, and subtle cerebellar ataxia, with nearly resolution after penicillamine treatment. Educational Value: This case highlights a typical aspect of WD, emphasizing the importance of early detection and treatment, and its correlation with MRI findings. Highlights: This case highlights the typical wing-beating tremor in Wilson's disease and its correlation with the involvement of the dentato-rubro-thalamic pathway. The early diagnosis and initiation of treatment with penicillamine resulted in an excellent clinical and radiological response.
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Degeneração Hepatolenticular , Penicilamina , Humanos , Cobre/farmacologia , Degeneração Hepatolenticular/diagnóstico por imagem , Degeneração Hepatolenticular/tratamento farmacológico , Imageamento por Ressonância Magnética , Penicilamina/uso terapêutico , Tremor/diagnóstico por imagem , Tremor/tratamento farmacológico , Tremor/etiologiaRESUMO
PURPOSE: To evaluate the structural and functional changes in eyes with neovascular age related macular degeneration (nAMD) in a real-world setting, using Treat and Extend protocol (T&E), comparing four antiangiogenic agents. METHODS: Prospective, observational, case series study performed in 131 patients with the exudative form of nAMD. Patients were randomly assigned into four groups according to the antiangiogenic agent. During the first year, all eyes received at least 3 monthly intravitreal injections of antiangiogenic agents, and afterwards, were submitted to the T&E. RESULTS: There was statistically significant difference (p < 0.05) between pre- and post-treatment in the best corrected visual acuity measurements by drug used. Patients who used aflibercept had significantly fewer injections than patients using the other drugs (mean = 9.03). No significant difference was observed between the drugs bevacizumab, ranibizumab and ziv-aflibercept. With regard to biomarkers, patients who used aflibercept and had lower baseline central retinal thickness, absence of hyperreflective foci and no subretinal hyperreflective material had the lowest number of injections. CONCLUSION: Results indicate that over 2 years, Intravitreal aflibercept on T&E provided better visual and anatomical improvements when compared to other drugs used in this study with significantly fewer injections.
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Atypical parkinsonism (AP) is a group of complex neurodegenerative disorders with marked clinical and pathophysiological heterogeneity. The use of systems biology tools may contribute to the characterization of hub-bottleneck genes, and the identification of its biological pathways to broaden the understanding of the bases of these disorders. A systematic search was performed on the DisGeNET database, which integrates data from expert curated repositories, GWAS catalogues, animal models and the scientific literature. The tools STRING 11.0 and Cytoscape 3.8.2 were used for analysis of protein-protein interaction (PPI) network. The PPI network topography analyses were performed using the CytoHubba 0.1 plugin for Cytoscape. The hub and bottleneck genes were inserted into 4 different sets on the InteractiveVenn. Additional functional enrichment analyses were performed to identify Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology for a described set of genes. The systematic search in the DisGeNET database identified 485 genes involved with Atypical Parkinsonism. Superimposing these genes, we detected a total of 31 hub-bottleneck genes. Moreover, our functional enrichment analyses demonstrated the involvement of these hub-bottleneck genes in 3 major KEGG pathways. We identified 31 highly interconnected hub-bottleneck genes through a systems biology approach, which may play a key role in the pathogenesis of atypical parkinsonism. The functional enrichment analyses showed that these genes are involved in several biological processes and pathways, such as the glial cell development, glial cell activation and cognition, pathways were related to Alzheimer disease and Parkinson disease. As a hypothesis, we highlight as possible key genes for AP the MAPT (microtubule associated protein tau), APOE (apolipoprotein E), SNCA (synuclein alpha) and APP (amyloid beta precursor protein) genes.
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Redes e Vias Metabólicas , Transtornos Parkinsonianos , Mapas de Interação de Proteínas , Biologia de Sistemas , Humanos , Transtornos Parkinsonianos/genética , Transtornos Parkinsonianos/metabolismo , Redes e Vias Metabólicas/genética , Mapas de Interação de Proteínas/genética , Redes Reguladoras de Genes/genética , AnimaisRESUMO
Photobiomodulation (PBM) is a type of phototherapy that employs light-emitting diodes (LEDs) or low-power lasers to selectively administer specific wavelengths of visible light, ranging from 500 to 1000 nm, including near-infrared (NIR) wavelengths. LEDs are advantageous compared to lasers due to their ability to treat large areas at a lower cost, lack of tissue damage potential in humans, and reduced risk of eye-related accidents. The ophthalmology community has recently taken interest in PBM as a promising novel approach for managing various retinal conditions such as age-related macular degeneration, retinopathy of prematurity, retinitis pigmentosa, diabetic retinopathy, Leber's hereditary optic neuropathy, amblyopia, methanol-induced retinal damage, and potentially others. This review critically assesses the existing body of research on PBM applications in the retina, focusing on elucidating the underlying mechanisms of action and evaluating the clinical outcomes associated with this therapeutic modality.
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PURPOSE: To describe the association of serous maculopathy with absence of retinal pigment epithelium (SMARPE) and large drusen in patients with non-neovascular age-related macular degeneration (AMD). METHODS: A retrospective study of ophthalmic examination and multimodal imaging data of individuals with SMARPE and large drusen observed over a period of 12-month was accomplished. SMARPE was defined as subretinal accumulation of fluid within the macular area due to retinal pigment epithelium (RPE) aperture. Large drusen were identified by the presence of sub-RPE deposits using multimodal imaging analysis (color fundus photography, fundus autofluorescence, and spectral-domain optical coherence tomography). RESULTS: Twelve eyes of 7 white patients with a mean age of 77 years were observed to have SMARPE associated with large drusen. The median visual acuity was 20/100. Bilateral SMARPE lesions were observed in 71% of study patients. All SMARPE lesions were hypoautofluorescent, located in the subretinal space between the RPE and the ellipsoid zone, and presented as complete or incomplete RPE apertures associated with subretinal fluid. The SMARPE in this study had coincident multimodal imaging features as the SMARPE described in other reports in the literature. CONCLUSIONS: Bilateral SMARPE can occur in association with typical AMD large drusen. Anomalisms resulting in drusen biogenesis or mechanisms that act alongside to these may be related to SMARPE development.
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Management of vitreoretinal disorders (e.g., neovascular age-related macular degeneration [nAMD] and diabetic macular edema [DME]) have assumed the standard therapy of lifelong anti-VEGF injections with drugs like aflibercept, brolucizumab, ranibizumab and bevacizumab. However, the burden imposed on patients is a major deterrent for continual therapy and recovery. Faricimab, a bispecific antibody, blocking both VEGF-A and Ang-2 molecules, produces a comparable functional and anatomical results, with less injections, significantly reducing patient burden. Visual acuity, safety, adverse effects, and anatomical outcomes are discussed in the pivotal clinical trials (YOSEMITE/RHINE and TENAYA/LUCERNE), and early data from real-world studies (TRUCKEE, TAHOE, FARWIDE-DME, FARETINA and others). In YOSEMITE and RHINE, faricimab demonstrated non-inferior vision gains, better anatomical outcomes compared to aflibercept every 8 weeks. Faricimab in the personalized treatment interval (PTI), after week 96, achieved 12-week interval in 78.1% of the patients and 16-week interval in 62.3%. TENAYA and LUCERNE reported comparable best corrected visual acuity (BCVA) improvement and better anatomic outcomes during head-to-head phase, parallel to aflibercept, at its 8-week treatment schedule. Faricimab in the PTI regimen, after week 96 achieved 12-week interval in 77.8% of the patients and 16-week interval in 63.1%. Safety of faricimab has been comparable to aflibercept in these pivotal trials. Real-world data supports the data from the pivotal studies regarding the efficacy and safety profile of faricimab in heterogenous real world patient population. Moreover, in previously treated patients, it also demonstrated a faster fluid resolution, good safety profile. Considering faricimab has demonstrated anatomic and durability benefit in the treatment of nAMD and DME, additional data from ongoing extension clinical trials, AVONELLE-X and RHONE-X will help understand longer term outcomes for patients treated with faricimab as well as patients switching from aflibercept to faricimab after finishing the pivotal trials. Longer term data from the real-world studies will also continue to contribute to our understanding of long-term efficacy, safety and durability in the real world patient population.
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The muscle is the principal tissue that is capable to transform potential energy into kinetic energy. This process is due to the transformation of chemical energy into mechanical energy to enhance the movements and all the daily activities. However, muscular tissues can be affected by some pathologies associated with genetic alterations that affect the expression of proteins. As the muscle is a highly organized structure in which most of the signaling pathways and proteins are related to one another, pathologies may overlap. Duchenne muscular dystrophy (DMD) is one of the most severe muscle pathologies triggering degeneration and muscle necrosis. Several mathematical models have been developed to predict muscle response to different scenarios and pathologies. The aim of this review is to describe DMD and Becker muscular dystrophy in terms of cellular behavior and molecular disorders and to present an overview of the computational models implemented to understand muscle behavior with the aim of improving regenerative therapy.
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Distrofia Muscular de Duchenne , Distrofia Muscular de Duchenne/metabolismo , Distrofia Muscular de Duchenne/patologia , Humanos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Animais , Simulação por Computador , Modelos BiológicosRESUMO
Testicular degeneration (TD) is the most frequent cause of sub or infertility in stallions. Currently, mesenchymal stem cells (MSC) have been studied as a therapeutic option for several diseases including induced-TD in laboratory animals. Therefore, this study aimed to evaluate the effect of intratesticular MSC therapy on the testicular histology of stallions submitted to scrotal heat stress. Ten healthy Miniature-horse stallions were submitted to testicular heat stress induced by a heating wrap device (42-45°C). Afterward, the stallions were divided into two groups and treated seven days later. MSCs-treated stallions were treated with an intratesticular injection of 10 × 106 of MSCs diluted in 5 mL of PBS, whereas placebo-treated stallions had 5 mL of PBS intratesticular injected. All stallions had testicular biopsies collected seven days before and one- and 14-days post-heat stress and were castrated 30 days after testicular insult. Tissue sections were stained with H&E and evaluated for the tubular and luminal diameter, epithelial thickness, seminiferous tubules (STs) integrity, the number of spermatozoa in the STs, and the percent of abnormal STs. Significance was set at P≤0.05. In both groups, testicular heat stress damaged the STs (P<0.05). However, STs' parameters were improved in MSCs-treated stallions compared to placebo-treated stallions 30 days after the testicular insult (P<0.05). In conclusion, the results of the present study suggest that intratesticular MSC therapy provided a therapeutic advantage in rescuing acute TD in stallions. However, further studies are essential to evaluate the benefits of this therapy on semen parameters and stallions with idiopathic TD.
Assuntos
Células-Tronco Mesenquimais , Testículo , Cavalos , Animais , Masculino , Espermatozoides , SêmenRESUMO
PURPOSE: To report a case of exudative perifoveal exudative vascular anomalous complex (ePVAC) in a Brazilian healthy patient that underwent a complete resolution after aflibercept intravitreal injections. CASE DESCRIPTION: A 41-year-old healthy Brazilian man complained of acute central vision loss in his right eye (RE). Fundus examination showed a perifoveal hemorrhagic aneurysmal lesion, accompanied by several hard exudates in RE. On fluorescein angiography, these abnormalities showed a progressive hyperfluorescence with surrounding leakage. Optical coherence tomography (OCT) revealed a deep, perifoveal hyporeflective cystic space with a hyperreflective wall and hyperreflective material inside of fibrin-like aspect. Around this aneurism, intraretinal hyporeflective spaces suggestive of exudation were detected. Nor pathological flow signal, or telangiectatic dilations were evidenced on OCT-angiography. Therefore, a diagnosis of exudative ePVAC in RE was hypothesized. After an initial observation, the patient underwent three monthly aflibercept intravitreal injections (0.05â ml/2â mg), with a significative anatomical and functional improvement after two weeks from first dose. On last follow-up at five months from baseline, patient experienced no evidence of new exudation and a stable visual acuity. DISCUSSION: Placental growth factor (PlGF) may impact on pericytes' dropout, and thus on ePVAC development. In contrast to the other anti-VEGF drugs, aflibercept is the only molecule contrasting PlGF. Therefore, aflibercept would act on ePVAC not as an anti-VEGF drug, but rather as an anti-PlGF one. CONCLUSION: This report encouraged the use of aflibercept as a therapeutic option for ePVAC. Further studies are required to confirm our result and the impact of PlGF on ePVAC pathogenesis.