Adipose-derived stromal cell therapy combined with a short course nonmyeloablative conditioning promotes long-term graft tolerance in vascularized composite allotransplantation.

The risks of chronic immunosuppression limit the utility of vascularized composite allotransplantation (VCA) as a reconstructive option in complex tissue defects. We evaluated a novel, clinically translatable, radiation-free conditioning protocol that combines anti-lymphocyte serum (ALS), tacrolimus, and cytotoxic T-lymphocyte-associated protein 4 immunoglobulin (CTLA4-Ig) with adipose-derived stromal cells (ASCs) to allow VCA survival without long-term systemic immunosuppression. Full-mismatched rat hind-limb-transplant recipients received tacrolimus (0.5 mg/kg) for 14 days and were assigned to 4 groups: controls (CTRL) received no conditioning; ASC-group received CTLA4-Ig (10 mg/kg body weight i.p. postoperative day [POD] 2, 4, 7) and donor ASCs (1 × 106 iv, POD 2, 4, 7, 15, 28); the ASC-cyclophosphamide (CYP)-group received CTLA4-Ig, ASC plus cyclophosphamide (50 mg/kg ip, POD 3); the ASC-ALS-group received CTLA4-Ig, ASCs plus ALS (500 µL ip, POD 1, 5). Banff grade III or 120 days were endpoints. ASCs suppressed alloresponse in vitro. Median rejection-free VCA survival was 28 days in CTRL (n = 7), 34 in ASC (n = 6), and 27.5 in ASC-CYP (n = 4). In contrast, ASC-ALS achieved significantly longer, rejection-free VCA survival in 6/7 animals (86%), with persistent mixed donor-cell chimerism, and elevated systemic and allograft skin Tregs , with no signs of acute cellular rejection. Taken together, a regimen comprised of short-course tacrolimus, repeated CTLA4-Ig and ASC administration, combined with ALS, promotes long-term VCA survival without chronic immunosuppression.

The effect of pH on cell viability, cell migration, cell proliferation, wound closure, and wound reepithelialization: In vitro and in vivo study.

Wound microenvironment plays a major role in the process of wound healing. It contains various external and internal factors that participate in wound pathophysiology. The pH is an important factor that influences wound healing by changing throughout the healing process. Several previous studies have investigated the role of pH in relation to pathogens but studies concentrating on the effects of pH on wound healing itself are inconclusive. The purpose of this study was to comprehensively and in a controlled fashion investigate the effect of pH on wound healing by studying its effect on human primary keratinocyte and fibroblast function in vitro and on wound healing in vivo. In vitro, primary human keratinocytes and fibroblasts were cultured in different levels of pH (5.5-12.5) and the effect on cell viability, proliferation, and migration was studied. A rat full-thickness wound model was used to investigate the effect of pH (5.5-9.5) on wound healing in vivo. The effect of pH on inflammation was monitored by measuring IL-1 α concentrations from wounds and cell cultures exposed to different pH environments. Our results showed that both skin cell types tolerated wide range of pH very well. They further demonstrated that both acidic and alkaline environments decelerated cell migration in comparison to neutral environments and interestingly alkaline conditions significantly enhanced cell proliferation. Results from the in vivo experiments indicated that a prolonged, strongly acidic wound environment prevents both wound closure and reepithelialization while a prolonged alkaline environment did not have any negative impact on wound closure or reepithelialization. Separately, both in vitro and in vivo studies showed that prolonged acidic conditions significantly increased the expression of IL-1 α in fibroblast cultures and in wound fluid, whereas prolonged alkaline conditions did not result in elevated amounts of IL-1 α.

Precision in Dermal Filling: A Comparison Between Needle and Cannula When Using Soft Tissue Fillers.

BACKGROUND: Precise implantation of soft tissue fillers to treat the signs of aging is crucial for patient safety and the best aesthetic outcome. Injections are performed commonly with either needles or cannulas, but quantitative comparative data on precise implantation are still elusive. METHODS: Ten fresh-frozen cephalic foreheads (9 male, 1 female) were injected with radiopaque material using both needles and cannulas. Needle injection relied on a perpendicular transcutaneous approach, whereas cannulas were moved in the supra-periosteal plane until reaching the same location as the needle. Two-dimensional distribution of the material in the horizontal and in the vertical axes was quantified using fluoroscopic imaging. Additional CT and MR imaging was performed to confirm results. RESULTS: The two-dimensional extent of injected material in the horizontal plane was 25.6 mm±10.5 mm vs 13.5 mm ± 6.5 mm (cannula vs needle; P=0.006) and 3.0 mm ± 0.90 mm vs 3.99 mm ± 0.97 mm (cannula vs needle; P=0.028) in the vertical plane. In 60% of injections using a needle, the implanted material changed its plane; this was not observed when using the cannula (0%; P=0.003). Retrograde backflow, however, was greater with a cannula (90.2%) compared to a needle (33.3%). CONCLUSIONS: If precision in filler injection is defined as the filler material remaining in the plane of intended implantation, then using cannulas resulted in a more precise injection of material as compared to needles. Applications with needles resulted in the distribution of material into more superficial layers, which was not noted for cannulas.

J Drugs Dermatol. 2017;16(9):866-872.

[The Emerging Interest in Breast Implant Illness and its impact on Patient Behavior]. / Das wachsende Interesse an Breast Implant Illness und dessen Einfluss auf das Verhalten der Patientinnen.

Breast implant illness (BII) is a loosely defined term for a collection of non-specific systemic symptoms that are hypothesised to be associated with breast implants. BII symptoms include fatigue, hair loss, rashes, chronic pain, and others. However, conclusive evidence for a causal relationship between silicone implants and BII remains lacking. In the light of recent findings that textured implants can, in rare cases, lead to breast implant-associated anaplastic large cell lymphoma (BIA-ALCL), a potential link between breast implants and BII is conceivable and justifies further investigation. We observe a growing number of patients seeking consultation and treatment for systemic symptoms related to breast implants, which is reflected in increasing interest in literature and social media. The aim of this work was to investigate the growing interest in BII. We now describe the clinical features of a patient who suffers from symptoms that are consistent with BII and contextualise clinical presentation in a review of literature and google trend analysis.

The Functional Anatomy of the Deep Facial Fat Compartments: A Detailed Imaging-Based Investigation.

BACKGROUND: Injection of soft-tissue fillers into the facial fat compartments is frequently performed to ameliorate the signs of facial aging. This study was designed to investigate the functional anatomy of the deep facial fat compartments and to provide information on the effects of injected material in relation to age and gender differences. METHODS: Forty fresh frozen cephalic specimens of 17 male and 23 female Caucasian body donors (mean age, 76.9 ± 13.1 years; mean body mass index, 23.6 ± 5.3 kg/m(2)) were investigated. Computed tomographic and magnetic resonance imaging procedures were carried out using colored contrast-enhanced materials with rheologic properties similar to commercially available soft-tissue fillers. Anatomical dissections were performed to guide conclusions. RESULTS: No statistically significant influences of age or gender were detected in the investigated sample. Increased amounts of injected contrast agent did not correlate with inferior displacement of the material in any of the investigated compartments: deep pyriform, deep medial cheek, deep lateral cheek, deep nasolabial (located within the premaxillary space), and the medial and lateral sub-orbicularis oculi fat. CONCLUSIONS: Increasing volume in the deep midfacial fat compartments did not cause inferior displacement of the injected material. This underscores the role of deep soft-tissue filler injections (i.e., in contact with the bone) in providing support for overlying structures and resulting in anterior projection.

The Functional Anatomy of the Superficial Fat Compartments of the Face: A Detailed Imaging Study.

BACKGROUND: The superficial (subcutaneous) facial fat compartments contribute to the signs of facial aging, but a comprehensive anatomical description of their location and their functional behavior during the application of soft-tissue fillers remains elusive. METHODS: The authors investigated 30 fresh frozen cephalic specimens from 13 male and 17 female Caucasian body donors (age, 78.3 ± 14.2 years; body mass index, 23.1 ± 5.3 kg/m(2)). Upright-position, contrast-enhanced computed tomographic scanning, and additional magnetic resonance imaging were performed. Three-dimensional reconstruction-based measures were conducted to evaluate the position of the applied contrast agent in each compartment separately. Successive anatomical dissections were performed to confirm the imaging findings. RESULTS: Positive correlations were detected between the amounts of injected material and the inferior displacement for the superficial nasolabial (rp = 0.92, p = 0.003), middle cheek (rp = 0.70, p = 0.05), and jowl (rp = 0.92, p = 0.03) compartments but not for the medial cheek (rp = 0.20, p = 0.75), lateral cheek (rp = 0.15, p = 0.75), or the superior (rp = -0.32, p = 0.41) or inferior superficial temporal compartment (rp = -0.52, p = 0.29). CONCLUSION: This study confirms the presence of distinct subcutaneous fat compartments and provides evidence for an individual behavior when soft-tissue fillers are applied: inferior displacement of the superficial nasolabial, middle cheek, and jowl compartments, in contrast to an increase in volume without displacement (i.e., an increase in projection) of the medial cheek, lateral cheek, and both superficial temporal compartments.

The Anatomy behind Adverse Events in Hand Volumizing Procedures: Retrospective Evaluations of 11 Years of Experience.

BACKGROUND: To retrospectively evaluate the rate of adverse events after hand volumizing procedures using a calcium hydroxylapatite product and to investigate the relationship between injector used (i.e., needle versus cannula) and technique applied (i.e., bolus, tenting, proximal-to-distal fanning, distal-to-proximal single line). METHODS: Two hundred twenty individuals, including 214 women (97.3 percent) aged 52.3 ± 11.4 years, treated bilaterally for hand rejuvenation were investigated between the years 2006 and 2017. Cadaveric dissections (n = 12), fluoroscopic (n = 4), ultrasound (n = 22), and computed tomographic (n = 4) imaging were also performed to guide conclusions. RESULTS: Thirty-two of 440 hands (7.3 percent) developed adverse events within the first 15 days, with swelling in 11 (5 percent), pain in four (1.8 percent), erythema in three (1.4 percent), and discoloration in one (0.5 percent). Using a needle (versus a cannula) was significantly related to the occurrence of adverse events (OR, 7.57; 95 percent CI, 3.76 to 15.24; p < 0.001). The proximal-to-distal fanning technique with access to the dorsal superficial lamina was identified as a safer application technique, with each of the other techniques having a significantly increased odds ratio for adverse events: bolus technique (OR, 26.9; 95 percent CI, 6.87 to 105.2; p < 0.001), tenting technique (OR, 24.73; 95 percent CI, 7.48 to 81.76; p < 0.001), and single-line technique (OR, 26.68; 95 percent CI, 7.45 to 95.48; p < 0.001). CONCLUSIONS: The results of this study support the use of cannula versus needle and the proximal-to-distal fanning technique. The underlying anatomy supports the positioning of the material into the subdermal space, which can be identified less than 1 mm deep to the skin surface, and is termed the dorsal superficial lamina.