Gene therapy has emerged as a research topic of choice in recent years. The eye in particular is one of few organs of the body for which gene therapy has received Food and Drug Administration approval, and it remains a field of great interest for gene therapy development. However, its associated immune and inflammatory reactions may render the treatment ineffective or harmful, which are of particular concern for the eyes due to their susceptibility to inflammation. The severity of immune and inflammatory reactions depends on the choice of vector and its route of administration. Furthermore, most preclinical and clinical studies have shown that the dose of vectors is correlated with the degree of humoral response and ocular inflammation. The route of administration directly impacts the degree of immune and inflammatory reaction. Subretinal delivery produces a weaker humoral response than the intravitreal route. However, some studies have demonstrated that the subretinal delivery induces a stronger inflammatory reaction. On the other hand, several instances of vision loss due to severe late onset intraocular inflammation were reported in a clinical trial involving intravitreal delivery of viral vectors. When compared with the intravitreal route, suprachoroidal gene delivery has been shown to produce weaker humoral response. However, unlike the subretinal space, the suprachoroidal space is not known to have immune privilege status. Inflammatory reactions following ocular gene therapy are typically mild and most clinical and preclinical studies have shown that they can be controlled with topical, local or systemic steroids. However, severe inflammatory responses may occur and require aggressive management to avoid permanent vision loss. Further investigations are required to elucidate and expand our knowledge of inflammatory reactions, and their optimal management, following ocular gene therapy.
Background A wrong traditional belief persists among people that opium consumption beneficially affects cardiovascular disease and its risk factors. However, no evidence exists regarding the effect of opium consumption or cessation on the long-term risk of major adverse cardio-cerebrovascular events after coronary artery bypass grafting. We therefore aimed to evaluate the effect of persistent opium consumption after surgery on the long-term outcomes of coronary artery bypass grafting. Methods The study population consisted of 28,691 patients (20,924 men, mean age 60.9 years), who underwent coronary artery bypass grafting between 2007 and 2016 at our centre. The patients were stratified into three groups according to the status of opium consumption: never opium consumers ( n = 23,619), persistent postoperative opium consumers ( n = 3636) and enduring postoperative opium withdrawal ( n = 1436). Study endpoints were 5-year mortality and 5-year major adverse cardio-cerebrovascular events, comprising all-cause mortality, acute coronary syndrome, cerebrovascular accident and revascularisation. Results After surgery, 3636 patients continued opium consumption, while 1436 patients persistently avoided opium use. The multivariable survival analysis demonstrated that persistent post-coronary artery bypass grafting opium consumption increased 5-year mortality and 5-year major adverse cardio-cerebrovascular events by 28% (hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.06–1.54; P = 0.009) and 25% (HR 1.25, 95% CI 1.13–1.40; P < 0.0001), respectively. It also increased the 5-year risk of acute coronary syndrome by 34% (sub-distribution HR 1.34, 95% CI 1.16–1.55; P < 0.0001). Conclusions The present data suggest that persistent post-coronary artery bypass grafting opium consumption may significantly increase mortality, major adverse cardio-cerebrovascular events and acute coronary syndrome in the long term. Future studies are needed to confirm our findings.
Over the past two decades, we have witnessed the increasing use of photodynamic therapy (PDT) in the field of ocular oncology. Based on a review of the literature and our own experience, we herein review the role of PDT for the management of intraocular tumors. The discussion includes two main topics. First, we discuss the application of PDT for benign tumors, including circumscribed choroidal hemangioma, choroidal osteoma, retinal astrocytoma, retinal capillary hemangioma (retinal hemangioblastoma), and retinal vasoproliferative tumor. Second, we assess the role of PDT for malignant tumors, including choroidal melanoma and choroidal metastasis.
OBJECTIVES Coronary artery disease is becoming a major health concern in the young population. Male and female patients may experience different journeys after coronary artery disease events. We aimed to evaluate risk factors and compare outcomes between young male and female patients undergoing coronary artery bypass graft surgery (CABG). METHODS In this registry-based large sample size study, patients undergoing isolated CABG at a young age (premature isolated CABG) between 2007 and 2016 were included and followed up until 2020. Premature was defined as women and men younger than 55 years old. The main end points of the study were 7-year all-cause mortality and 7-year major adverse cardiovascular and cerebrovascular events (MACCEs). RESULTS Of a total of 24 428 patients who underwent CABG, 7217 patients (men-to-women ratio ≈4:1) with premature isolated CABG were included. The median follow-up duration was 78.5 months (75.2–81.6 months). The prevalence rates of diabetes mellitus, hypertension, dyslipidaemia and obesity were significantly higher in women than in men (58.3% vs 28.6%, 64.2% vs 38.5%, 69.7% vs 55.3% and 44.7 vs 23.9, respectively; all Ps < 0.05). The risk factor burden (mean of the risk factor count per year) was also higher among the female population. Diabetes mellitus was the common mortality predictor between men and women. In the subgroup analysis (interaction analysis in the adjusted model), hypertensive females had a higher rate of MACCE and a higher rate of mortality than hypertensive males; however, this difference was not significant in the non-hypertensive population. Opium addiction was a strong predictor of MACCE and all-cause mortality among men. Female patients had a higher rate of 7-year MACCE (hazard ratio, 1.33; 95% confidence interval, 1.16–1.51) and a higher rate of 7-year all-cause mortality (hazard ratio, 1.23; 95% confidence interval, 0.98–1.53). CONCLUSIONS The risk factor profile and predictors of outcomes were different between our female and male patients. Women carried a higher risk of events and mortality after CABG at a young age.
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Purpose Diopsys ® NOVA fixed-luminance flicker full-field electroretinogram (ffERG) device is a potential adjunct to conventional flicker ffERG testing for assessing cone cell function. Magnitude of measured electrical response is known to vary with pupil size in conventional ffERG testing. The index study characterizes the relationship between magnitude of measured electrical activity and pupil size, both pupil diameter and pupil area, for this device. Methods Seventeen patients (34 eyes) with no known ocular diseases were enrolled in the study. Electrophysiologic function of cone cells was evaluated using fixed-luminance flicker ffERG before and after dilation. Linear regression models, with inter-eye correlations controlled as fixed-effects, were used to characterize the effect of pupil dilation on the magnitude of the measured responses. Results Mean age of study patients was 33.5 (standard deviation 7.4 years), and 35.3% of the subjects were female. Mean value of electrical response magnitude was 10.07±2.79µV before dilation and 15.30±4.08µV after dilation. The correlations of ERG magnitude with pupil diameter and with pupil area were not significant for either dilated or undilated eyes considered separately but were highly significant (p<0.001) for dilated and undilated eyes considered in aggregate. ERG magnitude tended to increase by 1.08 µV for every 1 mm increase in pupillary diameter. Conclusion An increase in pupil size, both pupil diameter and pupil area, is significantly associated with an increase in flicker ffERG magnitude recorded by the Diopsys device, suggesting that pupil size should be measured and considered when making clinical judgments based on the flicker ffERGs recorded by the device, and that pupil size-specific reference ranges could improve the clinical utility of the device.
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