Suprachoroidal and Subretinal Injections of AAV Using Transscleral Microneedles for Retinal Gene Delivery in Nonhuman Primates.

Retinal gene therapy using adeno-associated viruses (AAVs) is constrained by the mode of viral vector delivery. Intravitreal AAV injections are impeded by the internal limiting membrane barrier, while subretinal injections require invasive surgery and produce a limited region of therapeutic effect. In this study, we introduce a novel mode of ocular gene delivery in rhesus macaques using transscleral microneedles to inject AAV8 into the subretinal or suprachoroidal space, a potential space between the choroid and scleral wall of the eye. Using in vivo imaging, we found that suprachoroidal AAV8 produces diffuse, peripheral expression in retinal pigment epithelial (RPE) cells, but it elicited local infiltration of inflammatory cells. Transscleral subretinal injection of AAV8 using microneedles leads to focal gene expression with transduction of RPE and photoreceptors, and minimal intraocular inflammation. In comparison, intravitreal AAV8 shows minimal transduction of retinal cells, but elicits greater systemic humoral immune responses. Our study introduces a novel mode of transscleral viral delivery that can be performed without vitreoretinal surgery, with focal or diffuse transgene expression patterns suitable for different applications. The decoupling of local and systemic immune responses reveals important insights into the immunological consequences of AAV delivery to different ocular compartments surrounding the blood-retinal barrier

Health-related quality of life after fast-track treatment results from a randomized controlled clinical equivalence trial

Purpose This randomized clinical equivalence trial was designed to evaluate health-related quality of life (HRQoL) after fast-track treatment for low-risk coronary artery bypass (CABG) patients. Methods Four hundred and ten CABG patients were randomly assigned to undergo either short-stay intensive care treatment (SSIC, 8 h of intensive care stay) or control treatment (care as usual, overnight intensive care stay). HRQoL was measured at baseline and 1 month, and one year after surgery using the multidimensional index of life quality (MILQ), the EQ-5D, the Beck Depression Inventory and the State-Trait Anxiety Inventory. Results At one month after surgery, no statistically significant difference in overall HRQoL was found (MILQ-score P-value = .508, overall MILQ-index P-value = .543, EQ-5D VAS P-value = .593). The scores on the MILQ-domains, physical, and social functioning were significantly higher at one month postoperatively in the SSIC group compared to the control group (P-value = .049; 95% CI: 0.01-2.50 and P-value =.014, 95% CI:0.24-2.06, respectively). However, these differences were no longer observed at long-term follow-up. Conclusions According to our definition of clinical equivalence, the HRQoL of SSIC patients is similar to patients receiving care as usual. Since safety and the financial benefits of this intervention were demonstrated in a previously reported analysis, SSIC can be considered as an adequate fast-track intensive care treatment option for low-risk CABG patients

Facial Anthropometric Measurements and Principles - Overview and Implications for Aesthetic Treatments

Facial anatomy is highly individual in each patient. Anthropometric measurements can be a useful tool to objectively analyze individual facial anatomy to allow for better comparability before and after treatments to ultimately improve standardization of facial procedures, both nonsurgical and surgical. The aim of this study was to provide a comprehensive overview over clinically relevant and feasible facial anthropometric measurements and principles for aesthetic medicine. A literature review was conducted to describe the most important and clinically relevant anthropometric measurements and principles for both the entire face and for three aesthetically relevant facial regions: the periorbital region, the nose, and the perioral region. A multitude of different anthropometric measurements and principles have been described in the literature for both the overall facial appearance and specific facial regions. Certain generally accepted anthropometric principles and proportions need to be respected to achieve aesthetic and harmonious results. For the overall facial appearance, a focus on symmetry, certain proportions, facial angles, and indices has been described. Principles and measurements were also described for the periorbital region, the nose, and the perioral region. Although attractiveness and aesthetic perception are subjective, objective evaluation of facial surface anatomy via anthropometric measurements can improve pre- and postinterventional analysis of the face and help the treating physician to individualize treatments, both nonsurgical and surgical

Strengthening Plastic Surgery in Europe - ESPRAS Survey at ESPRAS European Leadership Forum (ELF)

Background The Executive Committee (ExCo) of the European Society of Plastic, Reconstructive and Aesthetic Surgery (ESPRAS) organized a first ESPRAS European Leadership Forum (ELF) to facilitate international exchange and to provide a platform for international leaders and delegates of national societies of Plastic Surgery to discuss common challenges. The presented manuscript presents key findings in a first effort of international harmonization and cooperation. Materials and Methods Members of the executive (presidents, vice-presidents, secretary generals) and national delegates of Plastic Surgery national societies discussed hot topics in Plastic Surgery via the Zoom virtual conferencing system (Zoom Video Communications, Inc.). Attending participants responded to a virtual question & answer session with questions being displayed throughout the webinar. Results The challenges associated with Aesthetic Surgery performed by doctors who are not board-certified Plastic Surgeons and Breast Implant-Associated Anaplastic Large Cell Lymphoma (BIA-ALCL) were perceived as major hot topics within most national societies. Both topics were discussed vividly. Education in plastic surgery and a European fellowship program for young Plastic Surgeons was favored by a large majority of participants. The implementation of European registries for free flaps, implants and for breast reconstruction were supported by the majority of respondents. Conclusion The ESPRAS ELF provides a platform to propel international exchange and alliance, communication, education, research and future projects. A further virtual webinar with the topic Strategies for Strengthening and Defending Plastic Surgery against Others was suggested to be conducted in spring 2021

Aspirin and mortality from coronary bypass surgery

BACKGROUND: There is no therapy known to reduce the risk of complications or death after coronary bypass surgery. Because platelet activation constitutes a pivotal mechanism for injury in patients with atherosclerosis, we assessed whether early treatment with aspirin could improve survival after coronary bypass surgery. METHODS: At 70 centers in 17 countries, we prospectively studied 5065 patients undergoing coronary bypass surgery, of whom 5022 survived the first 48 hours after surgery. We gathered data on 7500 variables per patient and adjudicated outcomes centrally. The primary focus was to discern the relation between early aspirin use and fatal and nonfatal outcomes. RESULTS: During hospitalization, 164 patients died (3.2 percent), and 812 others (16.0 percent) had nonfatal cardiac, cerebral, renal, or gastrointestinal ischemic complications. Among patients who received aspirin (up to 650 mg) within 48 hours after revascularization, subsequent mortality was 1.3 percent (40 of 2999 patients), as compared with 4.0 percent among those who did not receive aspirin during this period (81 of 2023, P<0.001). Aspirin therapy was associated with a 48 percent reduction in the incidence of myocardial infarction (2.8 percent vs. 5.4 percent, P<0.001), a 50 percent reduction in the incidence of stroke (1.3 percent vs. 2.6 percent, P=0.01), a 74 percent reduction in the incidence of renal failure (0.9 percent vs. 3.4 percent, P<0.001), and a 62 percent reduction in the incidence of bowel infarction (0.3 percent vs. 0.8 percent, P=0.01). Multivariate analysis showed that no other factor or medication was independently associated with reduced rates of these outcomes and that the risk of hemorrhage, gastritis, infection, or impaired wound healing was not increased with aspirin use (odds ratio for these adverse events, 0.63; 95 percent confidence interval, 0.54 to 0.74). CONCLUSIONS: Early use of aspirin after coronary bypass surgery is safe and is associated with a reduced risk of death and ischemic complications involving the heart, brain, kidneys, and gastrointestinal tract