To evaluate long-term visual and anatomical outcomes in neovascular age-related macular degeneration (nAMD) patients treated with anti-vascular endothelial growth factor (VEGF) agents depending on ...the time delay from confirmed diagnosis to treatment initiation.
Seventy-three nAMD patients (73 eyes) treated with anti-VEGF agents for 12 months using the pro re nata regimen were included in this retrospective longitudinal study. Patients were split into 3 groups according to the time from diagnosis to first anti-VEGF injection: < 48 h (group 1); 48 h-7 days (group 2); > 7 days (group 3). Decimal best-corrected visual acuity (VA) and macular thickness (MT) were recorded at baseline and 1–2-, 3–4-, 6- and 12-month later. Furthermore, age, gender as well as the applied treatment and number of injections after 12 months of treatment were also registered and compared.
Long-term effect of the treatment demonstrated enhanced VA in group 1 patients compared with the rest of groups after 1–2-, 6-, and 12-month follow-up (P < 0.05). Positive effects of early treatment were additionally corroborated by the augmented percentage of patients with normal VA in the group 1 respect to the rest of groups over studied time points (P < 0.05). Moreover, the VA gain in nAMD at group 1 was obtained with a mean of 3.7 intravitreal injections over 1-year follow-up period. Regarding MT, non-significant difference was observed among groups.
An early initial treatment with VEGF inhibitors is critical to achieve the best functional benefits of this therapy in new-onset nAMD patients.
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•Anti-VEGF therapy within 48 h from diagnosis leads to long-term visual gain in nAMD.•Visual gain is achieved with low IV injection number if early treatment is applied.•A prompt first anti-VEGF injection promotes long-term anatomical benefits in nAMD.
In recent years, the number of patients with ocular diseases is increasing as a consequence of population aging. Among them, one of the most common is the age-related macular degeneration (AMD), a ...condition that leads to vision loss if it is not treated. AMD is a multifactorial disorder with two advanced forms, dry and neovascular AMD. Currently, although there is no approved therapy that significantly impacts dry AMD progression, several pharmacologic therapies exist for neovascular AMD. Notwithstanding, evidence suggests a suboptimal result in a high number of patients receiving these therapeutic options. Consequently, finding effective strategies is not only a still unmet medical need in dry AMD but also in neovascular AMD. This underlines the need for new drug delivery technologies that can improve the pharmacological action and drug concentration at the target sites. In this regard, sustained drug delivery systems are presented as the most promising therapeutic options in AMD patients. This review summarized the pathogenesis and the current treatment options for AMD, focusing on the emerging ocular sustained drug delivery approaches undergoing clinical trials.
IntroductionThere is a need to find alternatives to the use of human donor corneas in transplants because of the limited availability of donor organs, the incidence of graft complications, as well as ...the inability to successfully perform corneal transplant in patients presenting limbal deficiency, neo-vascularized or thin corneas, etc. We have designed a clinical trial to test a nanostructured fibrin-agarose corneal substitute combining allogeneic cells that mimics the anterior human native cornea in terms of optical, mechanical and biological behaviour.Methods and analysisThis is a phase I-II, randomised, controlled, open-label clinical trial, currently ongoing in ten Spanish hospitals, to evaluate the safety and feasibility, as well as clinical efficacy evidence, of this bioengineered human corneal substitute in adults with severe trophic corneal ulcers refractory to conventional treatment, or with sequelae of previous ulcers. In the initial phase of the trial (n=5), patients were sequentially recruited, with a safety period of 45 days, receiving the bioengineered corneal graft. In the second phase of the trial (currently ongoing), subjects are block randomised (2:1) to receive either the corneal graft (n=10), or amniotic membrane (n=5), as the control treatment. Adverse events, implant status, infection signs and induced neovascularization are evaluated as determinants of safety and feasibility of the bioengineered graft (main outcomes). Study endpoints are measured along a follow-up period of 24 months, including 27 post-implant assessment visits according to a decreasing frequency. Intention to treat, and per protocol, and safety analysis will be performed.Ethics and disseminationThe trial protocol received written approval by the corresponding Ethics Committee and the Spanish Regulatory Authority and is currently recruiting subjects. On completion of the trial, manuscripts with the results of phases I and II of the study will be published in a peer-reviewed journal.Trial registrationCT.gov identifier: NCT01765244 (Jan2013). EudraCT number: 2010-024290-40 (Dec2012).
Inflammatory and antimicrobial diseases constitute a major burden for society, and fighting them is a WHO strategic priority. Most of the treatments available to fight inflammatory diseases are ...anti-inflammatory drugs, such as corticosteroids or immunomodulators that lack cellular specificity and lead to numerous side effects. In addition to suppressing undesired inflammation and reducing disease progression, these drugs lessen the immune system protective functions. Furthermore, treating infectious diseases is more and more challenging due to the rise of microbial resistance to antimicrobial drugs. Thus, controlling the inflammatory process locally without compromising the ability to combat infections is an essential feature in the treatment of inflammatory diseases. We isolated three forms (DRS-DA2N, DRS-DA2NE, and DRS-DA2NEQ) of the same peptide, DRS-DA2, which belongs to the dermaseptin family, from the Mexican tree frog Pachymedusa dacnicolor. Interestingly, DRS-DA2N and DRS-DA2NEQ exhibit a dual activity by inducing the death of leukocytes as well as that of Gram-negative and Gram-positive bacteria, including multiresistant strains, without affecting other cells such as epithelial cells or erythrocytes. We showed that the death of both immune cells and bacteria is induced rapidly by DRS-DA2 and that the membrane is permeabilized, leading to the loss of membrane integrity. We also validated the capacity of DRS-DA2 to regulate the pool of inflammatory cells in vivo in a mouse model of noninfectious peritonitis. After the induction of peritonitis, a local injection of DRS-DA2N could decrease the number of inflammatory cells locally in the peritoneal cavity without inducing a systemic effect, as no changes in the number of inflammatory cells could be detected in blood or in the bone marrow. Collectively, these data suggest that this peptide could be a promising tool in the treatment of inflammatory diseases, such as inflammatory skin diseases, as it could reduce the number of inflammatory cells locally without suppressing the ability to combat infections.
Introducción. La lesión medular afecta la calidad de vida y el estado de salud de la persona que la padece. Por su parte, el uso de una silla de ruedas adecuada a las necesidades y características ...particulares de cada individuo puede aumentar los cuidados en la salud, prevenir complicaciones como las úlceras por presión e incrementar la calidad de vida. Objetivo: Valorar la percepción de la calidad de vida y dar seguimiento a la formación de úlceras por presión como indicadores del impacto que tiene un programa basado en las “Pautas de suministro de sillas de ruedas manuales en entornos de menores recursos” de la OMS. Material y Métodos. A un grupo piloto de lesionados medulares se les otorgó una silla de ruedas adecuada; se les aplicaron los cuestionarios CHART-SF y WHOQOL-BREF para medir su calidad de vida y se les hizo seguimiento del desarrollo de úlceras por presión durante 12 meses. Resultados. Los principales hallazgos fueron una mejor percepción de la movilidad en el CHART-SF, mientras que en el WHOQOL -BREF el grupo no percibió ningún cambio, ni positivo ni negativo, en su calidad de vida. Los pacientes no desarrollaron úlceras por presión durante el estudio. Conclusiones. Los cuestionarios aplicados no son suficientemente sensibles para medir la calidad de vida en pacientes con lesión medular.
Introducción. La lesión medular afecta la calidad de vida y el estado de salud de la persona que la padece. Por su parte, el uso de una silla de ruedas adecuada a las necesidades y características ...particulares de cada individuo puede aumentar los cuidados en la salud, prevenir complicaciones como las úlceras por presión e incrementar la calidad de vida.
Objetivo: Valorar la percepción de la calidad de vida y dar seguimiento a la formación de úlceras por presión como indicadores del impacto que tiene un programa basado en las “Pautas de suministro de sillas de ruedas manuales en entornos de menores recursos” de la OMS.
Material y Métodos. A un grupo piloto de lesionados medulares se les otorgó una silla de ruedas adecuada; se les aplicaron los cuestionarios CHART-SF y WHOQOL-BREF para medir su calidad de vida y se les hizo seguimiento del desarrollo de úlceras por presión durante 12 meses.
Resultados. Los principales hallazgos fueron una mejor percepción de la movilidad en el CHART-SF, mientras que en el WHOQOL -BREF el grupo no percibió ningún cambio, ni positivo ni negativo, en su calidad de vida. Los pacientes no desarrollaron úlceras por presión durante el estudio.
Conclusiones. Los cuestionarios aplicados no son suficientemente sensibles para medir la calidad de vida en pacientes con lesión medular.
Shoulder pain is a highly prevalent condition, often resulting in major life limitations, and requiring effective treatments. In this work, we explore the anatomical basis of a proposed approach to ...the regional anesthesia of the shoulder through a single injection under the subscapularis muscle. Bilateral experimental injections in shoulders from body donors (Radiolar ® and Methylene-Blue) under the subscapular muscle (n = 11) and cadaveric systematic dissections of other 35 shoulders from body donors were performed. Injectate spread was then qualitatively assessed. Long axis of permeable foramina in the anterior aspect of the shoulder joint capsule was measured in centimeters using a digital caliper. More than 40% of specimens had at least one permeable space (Weitbrech and/or Rouvière foramina) communicating the subscapular bursa and the articular space. We further demonstrate that an ultrasonography-guided injection under the subscapularis muscle allows the spread of the injectate through the anterior, inferior and posterodorsal walls of the articular capsule, the subacromial bursa, and the bicipital groove, as well as into the articular space for some injections. The odds of accidental intraarticular injection decrease when injecting with low volumes. This anatomical study provides a detailed description of foramina between glenohumeral ligaments. Furthermore, the data shown in this work supports, as a proof of concept, a safe alternative for rapid and specific blockade of terminal sensory branches innervating the shoulder joint capsule.
Introducción: el Síndrome de Imerslund-Gransbeck es un trastorno congénito inusual que cursa con disminución de la Vitamina B12, anemia megaloblástica y proteinuria sin afección ren al que cual se ...produce por una mutación de los cromosomas 10 y 14, que condicionan un defecto en el receptor del complejo vitamina B12-factor intrínseco del enterocito ileal. Fue descrita por Olga Imerslund y Armas Gransbeck. Objetivo: caracterizar a la población que ha padecido el Síndrome de Imerslund-Gransbeck. Metodología: revisión sistemática de la literatura de casos clín icos. Resultados: se incluyeron 68 casos, en la mayoría de los casos el diagnostico en los primeros 10 años de vida, en el que se evidenció una mayor frecuencia en mujeres, y se encontró aso ciado con antecedentes familiares como consanguinidad entre padres (14,6%). La manifestación más frecuente fue palidez (20,9%), seguido de vomito (10,5%) y anorexia (9,8%). La anemia megaloblástica (66,2%) fue el hallazgo más frecuente y el tratamiento se dio con cianocobalamina (intramuscular u oral) para regular las concentraciones plasmáticas de esta vitamina. Conclusión: el Síndrome de Imerslund Gransbeck tiene una baja prevalencia y se presenta con mayor frecuencia en el continente europeo, tiene predilección por el sexo femenino y se caracteriza por una disminución de la vitamina B12 que pueden que puede predisponer a otras alteraciones como ataxia y retraso en el crecimiento. Palabras clave: Sindrome de Imerslund-Gransbeck; anemia megaloblástica recesiva; proteinuria; vitamina B12; cobalamina. Introduction: Imerslund-Gransbeck Syndrome is an unusual congenital disorder that causes a decrease in vitamin B12, megaloblastic anemia and proteinuria without kidney involvement that is caused by a mutation of chromosomes 10 and 14, which determine a defect in the complex receptor vitamin B12-ileal enterocyte intrinsic factor. It was described by Olga Imerslund and Armas Gransbeck. Objective: to characterize the population that has suffered from Imerslund Gransbeck syndrome. Methodology: systematic review of the clinical case literature. Results: 68 cases were included, in most cases the diagnosis in the first 10 years of life, in which a higher frequency was found in women, and was found to be associated with family history such as consanguinity between parents (14.6%). The most frequent manifestation was paleness (20.9%), followed by vomiting (10.5%) and anorexia (9.8%). Megaloblastic anemia (66.2%) was the most frequent finding and treatment was given with cyanocobalamin (intramuscular or oral) to regulate plasma concentrations of this vitamin. Conclusion: Imerslund-Gransbeck Syndrome has a low prevalence and occurs more frequently in the European continent, has a predilection for females and is characterized by a decrease in vitamin B12 that may predispose to other disorders such as ataxia and retardation in growth. Keywords: Imerslund-Gransbeck Syndrome; recessive megaloblastic anemia; proteinuria; vitamin B12; cobalamin.
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