Combining topical dermal infused exosomes with injected calcium hydroxylapatite for enhanced tissue biostimulation.

BACKGROUND: Exosome research continues to flourish. Subsequent knowledge surrounding indications, dose-response, safety, efficacy, and the ability to combine exosome treatment as a "skin primer"-for biostimulation modalities such as calcium hydroxylapatite (CaHA), platelet-rich plasma (PRP), and platelet-rich fibrin matrix (PRFM) is growing rapidly. The objective of this study was to develop safe, reproducible methods of improving topical exosome absorption to enhance the quality of skin either by themselves, or in combination with injectable CaHA. METHODS: Under IRB Approval (International Cell Surgical Society: ICSS-2022-007), 40 patients were enrolled in this study. Twenty patients underwent facial biostimulatory dermal infusion alone, to determine if this method allowed adequate exosome absorption. Five patients underwent facial biostimulatory infusion followed immediately by Dilute CaHA injection (1:1 dilution) to the face. Five patients underwent exosome biostimulatory dermal infusion followed immediately by hyperdilute CaHA (dilution 1:4) injection to the neck. Five patients underwent Facial Dilute CaHA injection (1:1 dilution) alone, without dermal infusion. Five patients underwent neck hyperdilute CaHA injection (1:4 dilution) alone, without dermal infusion. All patients had pretreatment Quantificare 3-D photo-documentation and skin analysis (Quantificare, France). In all patients, the skin was first cleansed with a gentle glycolic acid facial wash (Gregory MD). To induce a "homing inflammatory environment" for the exosomes, sea salt exfoliation was performed (SaltFacial®, SaltMed, Cardiff, CA). A nitric oxide-generating serum (N101 Pneuma Nitric Oxide, Austin, TX) was then applied to act as an enhanced vehicle for absorption. A 3 MHz ultrasound (SaltFacial®, SaltMed, Cardiff, CA) was then utilized to further deepen the absorption of the nitric oxide serum. A topical emulsion containing equal volumes (1.0 cc containing 1 million) of exosomes (Kimera Labs, Miramar, FL), 25 units of botulinum toxin (Xeomin, Merz Aesthetics, Raleigh, NC) and hyaluronic acid (Belatero, Merz Aesthetics, Raleigh, NC) was mixed via back-and-forth propulsion in a 3-cc syringe. When adequately mixed, the emulsion was then applied to the treatment areas. The cavitating ultrasound was then used to aid in the absorption of the emulsion. The patients were then treated with high-intensity LED therapy (SaltFacial®, SaltMed, Cardiff, CA), utilizing the collagen restoration preset program of combination red (660 nm) near-infrared (930 nm) wavelength for 20 min. Post-treatment Quantificare analysis was performed at 15 and 30 days after treatment. RESULTS: Without exception, all dermal infusion alone and CaHA injection alone patients showed an improvement in the tone, quality, and texture of their skin. Quantificare results showed consistent improvement in wrinkles, pores, skin evenness, improved vascularity, and a reduction in oiliness and unwanted pigment. When employed as a skin primer prior to injections (CaHA), enhanced and more rapid results were seen. CONCLUSIONS: Biostimulatory dermal infusion can be achieved utilizing topical placental mesenchymal stem cell-derived exosomes. These exosomes can be used alone, or mixed with ancillary ingredients such as botulinum toxin, hyaluronic acid dermal filler, and CaHA to customize and personalize treatments based upon individual patient needs. Topical absorption is enhanced with sea salt exfoliation, a topical nitric oxide-generating serum, and 3 MHz cavitating ultrasound. Post-absorption activity is enhanced with high-intensity LED treatment. The addition of CaHA injections after the topical exosome "priming of the skin" yielded enhanced skin quality faster than exosomes or CaHA alone.

Mesothelial Stem Cells and Stromal Vascular Fraction: Use in Functional Disorders, Wound Healing, Fat Transfer, and Other Conditions.

Autologous human fat-derived mesenchymal stem cells are present in stromal vascular fraction. Stromal vascular fraction can be easily and safely extracted from lipoaspirate. The regenerative, antiinflammatory and immunomodulatory effects of stromal vascular fraction are being documented in ongoing therapeutic response studies.

The Global Incidence of Appendicitis: A Systematic Review of Population-based Studies.

OBJECTIVE: We compared the incidence of appendicitis or appendectomy across the world and evaluated temporal trends. SUMMARY BACKGROUND DATA: Population-based studies reported the incidence of appendicitis. METHODS: We searched MEDLINE and EMBASE databases for population-based studies reporting the incidence of appendicitis or appendectomy. Time trends were explored using Poisson regression and reported as annual percent change (APC) with 95% confidence intervals (CI). APC were stratified by time periods and pooled using random effects models. Incidence since 2000 was pooled for regions in the Western world. RESULTS: The search retrieved 10,247 citations with 120 studies reporting on the incidence of appendicitis or appendectomy. During the 21st century the pooled incidence of appendicitis or appendectomy (in per 100,000 person-years) was 100 (95% CI: 91, 110) in Northern America, and the estimated number of cases in 2015 was 378,614. The pooled incidence ranged from 105 in Eastern Europe to 151 in Western Europe. In Western countries, the incidence of appendectomy steadily decreased since 1990 (APC after 1989=-1.54; 95% CI: -2.22, -0.86), whereas the incidence of appendicitis stabilized (APC=-0.36; 95% CI: -0.97, 0.26) for both perforated (APC=0.95; 95% CI: -0.25, 2.17) and nonperforated appendicitis (APC=0.44; 95% CI: -0.84, 1.73). In the 21st century, the incidence of appendicitis or appendectomy is high in newly industrialized countries in Asia (South Korea pooled: 206), the Middle East (Turkey pooled: 160), and Southern America (Chile: 202). CONCLUSIONS: Appendicitis is a global disease. The incidence of appendicitis is stable in most Western countries. Data from newly industrialized countries is sparse, but suggests that appendicitis is rising rapidly.

Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review.

BACKGROUND & AIMS: We conducted a systematic review to determine changes in the worldwide incidence and prevalence of ulcerative colitis (UC) and Crohn's disease (CD) in different regions and with time. METHODS: We performed a systematic literature search of MEDLINE (1950-2010; 8103 citations) and EMBASE (1980-2010; 4975 citations) to identify studies that were population based, included data that could be used to calculate incidence and prevalence, and reported separate data on UC and/or CD in full manuscripts (n = 260). We evaluated data from 167 studies from Europe (1930-2008), 52 studies from Asia and the Middle East (1950-2008), and 27 studies from North America (1920-2004). Maps were used to present worldwide differences in the incidence and prevalence of inflammatory bowel diseases (IBDs); time trends were determined using joinpoint regression. RESULTS: The highest annual incidence of UC was 24.3 per 100,000 person-years in Europe, 6.3 per 100,000 person-years in Asia and the Middle East, and 19.2 per 100,000 person-years in North America. The highest annual incidence of CD was 12.7 per 100,000 person-years in Europe, 5.0 person-years in Asia and the Middle East, and 20.2 per 100,000 person-years in North America. The highest reported prevalence values for IBD were in Europe (UC, 505 per 100,000 persons; CD, 322 per 100,000 persons) and North America (UC, 249 per 100,000 persons; CD, 319 per 100,000 persons). In time-trend analyses, 75% of CD studies and 60% of UC studies had an increasing incidence of statistical significance (P < .05). CONCLUSIONS: Although there are few epidemiologic data from developing countries, the incidence and prevalence of IBD are increasing with time and in different regions around the world, indicating its emergence as a global disease.