To elucidate the mechanism underlying high efficacy of aMSCγ therapy, we examined the secretome of aMSCγ and compared it to that of naive MSC. Intriguingly, we found that aMSCγ but not nMSC upregulated neuron-glia antigen 2, an important extracellular signal and a hallmark protein of oligodendrocyte progenitor cells. Conclusions These results suggest that activation of MSC with interferon-γ induces a potent proregenerative, promyelinating, and anti-inflammatory phenotype of these cells, which increases the potency of aMSCγ as an effective therapy for ischemic stroke.Background Concurrent presence of aortic stenosis and aortic regurgitation is termed mixed aortic valve disease (MAVD). Although multiple articles have addressed patients with "isolated" aortic stenosis or aortic regurgitation, the natural history, impact, and outcomes of MAVD are not well defined. Here, we evaluate long-term outcomes in patients with MAVD and cardiovascular adaptations to chronic MAVD. Methods and Results This observational cohort study evaluated 862 adult patients (56.8% male) with preserved left ventricular ejection fraction and at least moderate aortic regurgitation and moderate aortic stenosis. Primary outcome was all-cause mortality. Subgroup analysis was based on treatment modality (aortic valve replacement [AVR] versus medical management). A regression analysis of longitudinal echocardiographic parameters was performed to assess the natural history of MAVD. Mean age was 68±15 years, and mean left ventricular ejection fraction was 58±5%. At 4.6 years (25th-75th percentile range, 1.0-8.7), 58.6% of patients underwent an AVR and 48.8% patients died. In both unadjusted and adjusted Cox survival analysis, AVR was associated with improved survival (hazard ratio, 0.41; 95% CI, 0.34-0.51, P less then 0.001). Impact of AVR persisted when stratifying the cohort by symptom status and baseline aortic valve area (log rank, P less then 0.001 for both) and after propensity-score matching (hazard ratio, 0.40; 95% CI, 0.32-0.50; P less then 0.001). In the longitudinal analysis, there were statistically significant changes over time in aortic valve peak gradient (P less then 0.001) and aortic valve area (P less then 0.001) and only mild increases in left ventricular end-diastolic (P less then 0.007) and -systolic (P less then 0.001) volumes. Conclusions MAVD confers a high risk of all-cause mortality. However, AVR significantly reduces this risk independent of aortic valve area, symptom status, and after controlling for confounding variables.OBJECTIVES This study aims to compare the hearing preservation outcomes in cochlear implant surgery following slit versus full opening of the round window membrane. SETTING Tertiary referral center. STUDY DESIGN Comparative study. SUBJECTS AND METHODS Seventy patients (mean, 26.3 years; range, 2-69 years) who underwent cochlear implantation via the round window approach were included in the study. Thirty-five subjects were prospectively enrolled for cochlear implantation via the open round window technique between August 2018 and January 2019. Thirty-five patients who underwent cochlear implantation from January 2017 to July 2018 via the slit round window opening, frequency matched by sex and age, were retrospectively enrolled. Pre- and postoperative thresholds were obtained. The percentage of hearing preservation was computed with the HEARRING Network formula and classified into complete, partial, and minimal hearing preservation.  https://www.selleckchem.com/products/vx-661.html  The results between the groups were compared and analyzed at 6 months postoperatively. RESULTS The rate of complete hearing preservation in the open group was statistically significant (P = .030) at 71.4% (n = 25) as compared with 45.7% (n = 16) in the slit group. CONCLUSIONS The widely opened round window may be an optional technique that surgeons can utilize to improve hearing preservation outcomes.OBJECTIVE To describe the Trach Safe Initiative and assess its impact on unanticipated tracheostomy-related mortality in outpatient tracheostomy-dependent children (TDC). METHODS An interdisciplinary team including parents and providers designed the initiative with quality improvement methods. Three practice changes were prioritized (1) surveillance airway endoscopy prior to hospital discharge from tracheostomy placement, (2) education for community-based nurses on TDC-focused emergency airway management, and (3) routine assessment of airway events for TDC in clinic. The primary outcome was annual unanticipated mortality after hospital discharge from tracheostomy placement before and after the initiative. RESULTS In the 5 years before and after the initiative, 131 children and 155 children underwent tracheostomy placement, respectively. At the end of the study period, the institution sustained Trach Safe practices (1) surveillance bronchoscopies increased from 104 to 429 bronchoscopies, (2) the course trained 209 community-based nurses, and (3) the survey was used in 488 home ventilator clinic visits to identify near-miss airway events. Prior to the initiative, 9 deaths were unanticipated. After Trach Safe implementation, 1 death was unanticipated. Control chart analysis demonstrates significant special-cause variation in reduced unanticipated mortality. DISCUSSION We describe a system shift in reduced unanticipated mortality for TDC through 3 major practice changes of the Trach Safe Initiative. IMPLICATION FOR PRACTICE Death in a child with a tracheostomy tube at home may represent modifiable tracheostomy-related airway events. Using Trach Safe practices, we address multiple facets to improve safety of TDC out of the hospital.OBJECTIVE To determine the frequency at which patients with osteocutaneous free flap reconstruction of the head and neck develop long-term complications and identify predisposing perioperative factors. STUDY DESIGN A prospectively maintained database of free flaps performed at a single institution over a 10-year period was queried. SETTING Single tertiary care referral center. SUBJECTS AND METHODS In total, 250 osseous or osteocutaneous free flaps (OCFFs) for mandibular or maxillary reconstruction were analyzed. Data were collected on demographics, preoperative therapy, resection location, adjuvant treatment, complications, and subsequent surgeries, and multivariate analysis was performed. Subgroup analysis based on perioperative factors was performed. RESULTS The median follow-up time was 23 months. In 185 patients with at least 6 months of follow-up, 17.3% had at least 1 long-term complication, most commonly wound breakdown, fistula or plate extrusion (13.5%), osteoradionecrosis or nonunion (6.5%), and infected hardware (5.