APOE-ε4 synergizes with sleep disruption to accelerate Aß deposition and Aß-associated tau seeding and spreading.

Alzheimer's disease (AD) is the most common cause of dementia. The APOE-ε4 allele of the apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset AD. The APOE genotype modulates the effect of sleep disruption on AD risk, suggesting a possible link between apoE and sleep in AD pathogenesis, which is relatively unexplored. We hypothesized that apoE modifies Aß deposition and Aß plaque-associated tau seeding and spreading in the form of neuritic plaque-tau (NP-tau) pathology in response to chronic sleep deprivation (SD) in an apoE isoform-dependent fashion. To test this hypothesis, we used APPPS1 mice expressing human APOE-ε3 or -ε4 with or without AD-tau injection. We found that SD in APPPS1 mice significantly increased Aß deposition and peri-plaque NP-tau pathology in the presence of APOE4 but not APOE3. SD in APPPS1 mice significantly decreased microglial clustering around plaques and aquaporin-4 (AQP4) polarization around blood vessels in the presence of APOE4 but not APOE3. We also found that sleep-deprived APPPS1:E4 mice injected with AD-tau had significantly altered sleep behaviors compared with APPPS1:E3 mice. These findings suggest that the APOE-ε4 genotype is a critical modifier in the development of AD pathology in response to SD.

Establishment of Safety of Hemostatic Net Application Utilizing Laser-Assisted Fluorescence Angiography With SPY-Q Software Analysis.

BACKGROUND: The hemostatic net, which was initially described as a method to decrease hematoma rates in facelift and necklift procedures, has since increased in practice and applicability. However, despite its demonstrated safety and efficacy, there exists significant skepticism with regard to its necessity; in particular, there is concern that the transcutaneous sutures may restrict dermal perfusion. OBJECTIVES: The goal of this study was to assess flap perfusion, both before and after application of the hemostatic net, to determine if there was an objective decrease in tissue perfusion in relation to application of the hemostatic net, as measured by laser-assisted angiography (LAA). METHODS: Eight patients underwent cervicofacial flap reconstruction of cutaneous malignancy defects, after which a hemostatic net was applied. All patients underwent evaluation with LAA both before and after application of the net. The average relative and absolute perfusion of different zones of the flap were calculated. RESULTS: The average absolute change in relative perfusion was +6.41%, +0.31%, and +3.28% for zones 1, 2, and 3, respectively, after application of the hemostatic net. There was no statistical difference in relative tissue perfusion after application of the net. There were no instances of delayed healing, infections, ischemia, necrosis, or hematoma. One patient developed a seroma after the net was removed. No patients had scarring or residual track marks from the transcutaneous sutures. CONCLUSIONS: With LAA, we were able to objectively demonstrate no significant decrease in tissue perfusion after the application of the hemostatic net.

Total Intravenous Anesthesia With Dexmedetomidine for Hemodynamic Stability and Enhanced Recovery in Facial Aesthetic Surgery.

BACKGROUND: Patients undergoing facial rejuvenation surgery are at unique risk of perioperative complications from the anesthetic utilized during the procedure. The ideal anesthetic agent is one that is safe to use in the outpatient population, has analgesic, sedative, and anesthetic properties, yet does not cause respiratory depression or hemodynamic irregularities. OBJECTIVES: A retrospective analysis of a large outpatient facelift cohort was performed to determine if dexmedetomidine, an α 2-adrenergic receptor agonist, meets the criteria of an ideal adjunct for propofol in a total intravenous anesthesia protocol. METHODS: The charts of 791 patients who underwent rhytidectomy with total intravenous anesthesia were reviewed and data of patients' operative risk factors, perioperative management including medications administered, perioperative vital signs, and postoperative adverse events were recorded. Statistical univariate analyses were performed on the data. RESULTS: Dexmedetomidine resulted in a significant reduction and maintenance of blood pressure from onset of anesthesia until discharge from the postanesthetic recovery unit. The utilization of opioids and anxiolytics was significantly less than previously reported for other anesthetic types. The postoperative nausea/vomiting rate was 0.8% (6 patients). There were no postoperative admissions for inpatient management. Forty-three (5.3%) patients required a conversion to general endotracheal anesthesia and statistically significant risk factors include increased BMI, American Society of Anesthesiologists Class II or higher, preoperative hypertension, and multiple procedures performed. CONCLUSIONS: This study demonstrated the safety and efficacy of dexmedetomidine in a large cohort of outpatients undergoing facelift. Dexmedetomidine meets the requirements for an ideal adjunct anesthetic within a total intravenous anesthesia protocol.