RESUMEN
PURPOSE: To compare the efficacy and safety of the PRESERFLO™ MicroShunt versus trabeculectomy in patients with primary open-angle glaucoma (POAG) after one year. PATIENTS AND METHODS: Institutional prospective interventional cohort study comparing eyes with POAG, which had received the PRESERFLO™ MicroShunt versus trabeculectomy. The MicroShunt group was matched with the trabeculectomy group for age, known duration of disease, and number and classes of intraocular pressure (IOP) lowering medications to have similar conjunctival conditions. The study is part of the Dresden Glaucoma and Treatment Study, using a uniform study design, with the same inclusion and exclusion criteria, follow-ups and standardized definitions of success and failure for both procedures. PRIMARY OUTCOME MEASURES: mean diurnal IOP (mdIOP, mean of 6 measurements), peak IOP, and IOP fluctuations. SECONDARY OUTCOME MEASURES: success rates, number of IOP lowering medications, visual acuity, visual fields, complications, surgical interventions, and adverse events. RESULTS: Sixty eyes of 60 patients, 30 in each group, were analyzed after 1-year follow-ups. Median [Q25, Q75] mdIOP (mmHg) dropped from 16.2 [13.8-21.5] to 10.5 [8.9-13.5] in the MicroShunt and from 17.6 [15.6-24.0] to 11.1 [9.5-12.3] in the trabeculectomy group, both without glaucoma medications. Reduction of mdIOP (P = .596), peak IOP (P = .702), and IOP fluctuations (P = .528) was not statistically significantly different between groups. The rate of interventions was statistically significantly higher in the trabeculectomy group, especially in the early postoperative period (P = .018). None of the patients experienced severe adverse events. CONCLUSION: Both procedures are equally effective and safe in lowering mdIOP, peak IOP and IOP fluctuations in patients with POAG, one year after surgery. CLINICAL TRIAL REGISTRATION: NCT02959242.
Asunto(s)
Glaucoma de Ángulo Abierto , Glaucoma , Trabeculectomía , Humanos , Trabeculectomía/métodos , Glaucoma de Ángulo Abierto/cirugía , Glaucoma de Ángulo Abierto/tratamiento farmacológico , Estudios Prospectivos , Estudios de Cohortes , Glaucoma/cirugía , Presión Intraocular , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
PURPOSE: To report efficacy and safety outcomes of the PRESERFLO™ MicroShunt compared with trabeculectomy, the current gold-standard treatment for advanced glaucoma, in the early and intermediate postoperative period. METHODS: Institutional prospective interventional cohort study of primary open-angle glaucoma (POAG) patients scheduled for the PRESERFLO™ MicroShunt. The comparison group were POAG patients who had had received trabeculectomy and were matched for age, known duration of disease, number and classes of intraocular pressure (IOP)-lowering medications to ensure a similar conjunctival condition. The study is part of the Dresden Glaucoma and Treatment Study (DGTS), was not randomized, but used a uniform study design, with the same inclusion and exclusion criteria as well as standardized definitions of success and failure. MAIN OUTCOME MEASURES: mean diurnal IOP (mdIOP, mean of 6 measurements), diurnal peak IOP, diurnal IOP fluctuations, glaucoma medical therapy, success rates, visual acuity, visual fields, surgical complications and interventions, and severe adverse events. RESULTS: Fifty-two eyes of 52 patients, 26 in each group, were analysed. At 6 months, median [Q25, Q75] mdIOP was 10.8 [9.5-12.2] mmHg in the microshunt and 10.3 [7.6-11.8] mmHg in the trabeculectomy group. Reduction in mdIOP (p = 0.458), peak diurnal IOP (p = 0.539), and median diurnal fluctuation (p = 0.693) was not statistically significantly different between groups. The rate of interventions was statistically significantly higher in the trabeculectomy compared with the microshunt group (p = 0.004). None of the patients experienced severe adverse events. CONCLUSION: Both procedures are equally effective and safe in lowering mdIOP in patients with POAG. Because the microshunt is less invasive with less follow-up and interventions needed postoperatively, it might be recommended earlier in the treatment of glaucoma.
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Glaucoma de Ángulo Abierto , Glaucoma , Trabeculectomía , Estudios de Cohortes , Glaucoma/cirugía , Glaucoma de Ángulo Abierto/tratamiento farmacológico , Glaucoma de Ángulo Abierto/cirugía , Humanos , Presión Intraocular , Estudios Prospectivos , Estudios Retrospectivos , Trabeculectomía/métodos , Resultado del TratamientoRESUMEN
PURPOSE: To study the possible changes in Scheimpflug corneal densitometry 6 months after mitomycin C-augmented trabeculectomy and to compare these measurements with healthy controls. METHODS: Corneal densitometry was monitored with the Pentacam HR3 before and 6 months after first-time uncomplicated mitomycin C-augmented trabeculectomy in 42 eyes of 42 white patients with open-angle glaucoma and in 22 healthy age-matched controls. Preoperative intraocular pressure (IOP), central corneal thickness, known duration of the disease, gender, the type and number of substances, applications and amount of benzalkonium chloride per day, and postoperative topical cortisone use were tested for possible correlations in the trabeculectomy group. RESULTS: There was a statistically significant reduction of mean diurnal IOP from 19.0 ± 7.7 to 11.1 ± 7.7 mm Hg (P = 0.003) and the amount of pressure-lowering substances from 3.7 ± 1.0 to 0.1 ± 0.5 (P < 0.001). Densitometry measurements decreased in the entire cornea from 25.5 ± 5.7 to 23.1 ± 5.8 grayscale units (P = 0.001) with emphasis in the anterior layer. They returned close to normal 6 months after trabeculectomy and were not statistically significantly different compared with a healthy control group (22.8 ± 3.4 grayscale unit; P = 0.824). No correlations could be found with these observations and possible causing factors studied. CONCLUSIONS: Corneal densitometry, an objective and sensitive measure of corneal transparency, returned close to normal 6 months after trabeculectomy. Although the observations cannot be associated with any causing factor in this study, the significant IOP reduction and the nearly complete cessation of topical antiglaucomatous substances including benzalkonium chloride seem to be the most plausible reasons for this finding.
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Córnea/patología , Densitometría , Glaucoma de Ángulo Abierto/cirugía , Trabeculectomía , Anciano , Alquilantes/administración & dosificación , Recuento de Células , Femenino , Estudios de Seguimiento , Glaucoma de Ángulo Abierto/fisiopatología , Humanos , Presión Intraocular/fisiología , Masculino , Persona de Mediana Edad , Mitomicina/administración & dosificación , Tamaño de los Órganos , Tonometría Ocular , Agudeza Visual/fisiologíaRESUMEN
AIMS: Basal rate tests (24-hour fasting periods) may be necessary to optimize basal insulin replacement in type 1 diabetes. It was the aim of this study to prospectively compare the allowance of negligible carbohydrate snacks vs absolute fasting. METHODS: A total of 20 patients with type 1 diabetes (age, 48 ± 15 years (9 women, 11 men); BMI, 28.5 ± 4.5 kg/m2 ; HbA1c, 8.8% ± 2.0% (73.0 ± 21.9 mmol/mol); insulin dose, 0.69 ± 0.31 IU/kg body weight and per day) participated in 2 basal rate tests lasting 24 hours in random order with unchanged basal insulin replacement. On 1 occasion, negligible carbohydrate snacks (salads and vegetables, up to 5.1 g carbohydrate and 276.3 kJ per portion) were allowed; during the second test subjects were obliged to fast absolutely. Plasma glucose profiles were determined using an exact laboratory method. Hypoglycaemic episodes (plasma glucose < 70 mg/dL) were compared. RESULTS: Plasma glucose concentrations during fasting periods, with and without negligible carbohydrate snacks, did not differ significantly ( P = .65) and differences were negligible (95% confidence intervals always included a difference of 0 mmol/L). Also, there was no difference in the number of hypoglycaemic plasma glucose values (P = .40) or in compensatory carbohydrate intake. Basal rate testing with negligible carbohydrate snacks was better tolerated (questionnaire, P = .046) and the desire to discontinue the fasting period was significantly reduced (P = .023). CONCLUSIONS: Allowing negligible carbohydrate snacks results in unchanged plasma glucose profiles during basal rate testing and is better tolerated by patients with type 1 diabetes.
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Metabolismo Basal/fisiología , Glucemia/análisis , Diabetes Mellitus Tipo 1/metabolismo , Ayuno/metabolismo , Bocadillos/fisiología , Adulto , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/complicaciones , Carbohidratos de la Dieta/administración & dosificación , Femenino , Humanos , Hipoglucemia/sangre , Hipoglucemia/etiología , Hipoglucemia/metabolismo , Insulina/sangre , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Epithelial-mesenchymal transition (EMT) is a cellular development program characterized by loss of cell adhesion and increased cell mobility. It is essential for numerous processes including metastasis. In this study we have generated "aggressive" MCF-7 breast cancer cells (MCF-7-EMT), which show significantly increased invasion in contrast to wild type MCF-7 (MCF-7 WT) cells. In addition, we have analyzed, whether these cell lines differ in their metastatic behavior in vivo and in expression of invasion and/or EMT-relevant genes. Invasive behavior of different human breast cancer cell lines was tested. "Aggressive" MCF-7 cells (MCF-7-EMT) were generated using coculture and mammosphere culture techniques. To analyze whether or not MCF-7-EMT cells in contrast to MCF-7 WT cells form metastases in vivo, we assessed metastases in a nude mouse model. mRNA expression profiles of MCF-7 WT cells and MCF-7-EMT cells were compared using the Affymetrix micro array technique. Expression of selected genes was validated using real-time PCR. In addition, protein expression of epithelial marker E-cadherin (CDH1) and mesenchymal markers N-cadherin (CDH2), Vimentin (VIM), and TWIST was compared. The breast cancer cell lines showed different invasive behavior from hardly any invasion to a stronger cell movement. Coculture with osteoblast-like MG63 cells led to significantly increased cell invasion rates. The highest increase was shown using MCF-7 WT cells. Generated MCF-7-EMT cells showed significantly increased invasion as compared to MCF-7 WT cells. In 8 of 10 mice bearing orthotopically growing MCF-7-EMT tumors, we could detect metastases in liver and lung. In mice bearing MCF-7 WT tumors (n = 10), no metastases were found. MCF-7 WT cells and MCF-7-EMT cells were different in expression of 325 genes. Forty-four of the most regulated 50 invasion and/or EMT-related genes were upregulated and 6 genes were downregulated in MCF-7-EMT cells. Protein expression of mesenchymal markers CDH2, VIM, and TWIST was clearly increased in MCF-7-EMT cells. Protein expression of epithelial marker CDH1 was clearly decreased. With the breast cancer cell lines, MCF-7-EMT and MCF-7 WT cells, we have an excellent model of cells for further studies of EMT and invasion in vitro and in vivo.
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Biomarcadores de Tumor/genética , Neoplasias de la Mama/patología , Movimiento Celular , Transición Epitelial-Mesenquimal , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/secundario , Animales , Apoptosis , Biomarcadores de Tumor/metabolismo , Western Blotting , Neoplasias de la Mama/metabolismo , Cadherinas/metabolismo , Adhesión Celular , Proliferación Celular , Técnicas de Cocultivo , Femenino , Perfilación de la Expresión Génica , Humanos , Técnicas In Vitro , Neoplasias Hepáticas/metabolismo , Neoplasias Pulmonares/metabolismo , Células MCF-7 , Ratones , Ratones Desnudos , Invasividad Neoplásica , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVES: The cross talk between metastatic cancer cells and target sites is critical for the development and progression of metastases. Disruption of this interaction will allow to design mechanism-based effective and specific therapeutic interventions for metastases. We have established a coculture system of cells derived from different tumor entities and MG63 human osteoblastlike cells to analyze tumor cell invasion. Recently, we have shown that breast cancer cell invasion was dramatically increased when cocultured with MG63 cells.Using this model, we have now analyzed whether stromal-derived factor 1 (SDF-1) is responsible for human endometrial cancer cell invasion and whether kisspeptin-10 (KP-10) treatment affects SDF-1-induced invasion of endometrial cancer cells in vitro. METHODS: Invasion was quantified by assessment of endometrial cancer cell migration rate through an artificial basement membrane in a modified Boyden chamber during coculture with MG63 cells or after treatment with SDF-1α, SDF-1ß, or the combination of both SDF-1 isoforms. In addition, the role of SDF-1 in invasion of endometrial cancer cells was analyzed by blocking SDF-1 secretion during coculture with MG64 cells. Furthermore, the effects of KP-10 treatment on MG63 coculture-driven and SDF-1-induced invasion were analyzed. RESULTS: Endometrial cancer cell invasion was significantly increased when cocultured with MG63 cells. Treatment with KP-10 reduced the ability to invade a reconstituted basement membrane and to migrate in response to the cellular stimulus. This effect was significant in a dose window of 10(-13) to 10(-11) mol/L. During coculture, SDF-1 protein expression of MG63 cells was significantly increased. The MG63 coculture-induced increase of endometrial cancer cell invasion could be blocked by anti-SDF-1 antibodies. Treatment of endometrial cancer cells in monoculture (without MG63) with SDF-1α, SDF-1ß, or the combination of both isoforms resulted in a significant increase of endometrial cancer cell invasion. The SDF-1-induced increase of endometrial cancer cell invasion was significantly reduced after treatment with KP-10. CONCLUSIONS: Our findings suggest that SDF-1 plays a major role in endometrial cancer invasion. Stromal-derived factor 1-induced invasion can be inhibited by KP-10 treatment.