In vivo evaluation of 3D printed polycaprolactone composite scaffold and recombinant human bone morphogenetic protein-2 for vertical bone augmentation with simultaneous implant placement on rabbit calvaria.

This study evaluated 3D printed polycaprolactone (PCL) composite scaffold and recombinant human bone morphogenetic protein-2 (rhBMP-2), loaded either onto a PCL composite scaffold or implant surface, for vertical bone augmentation with implant placement. Three-dimensional printed PCL frames were filled with powdered PCL, hydroxyapatite, and ß-tricalcium phosphate. RhBMP-2 was loaded to the PCL composite scaffolds and implant surfaces, and rhBMP-2 release was quantified for 21 days. Experimental implants were placed bilaterally on 20 rabbit calvaria, and the PCL composite scaffolds were vertically augmented. The randomly allocated experimental groups were divided by carrier and rhBMP-2 dosage as no rhBMP-2 (control), 5 µg rhBMP-2 loaded to PCL composite (Scaffold/rhBMP-2[5 µg]), 5 µg rhBMP-2 loaded to implant (Implant/rhBMP-2[5 µg]), 30 µg rhBMP-2 loaded to PCL composite (Scaffold/rhBMP-2[30 µg]), and 30 µg rhBMP-2 loaded to implant (Implant/rhBMP-2[30 µg]). Histologic and histometric analyses were conducted after 8 weeks. In both scaffold-loading and implant-loading, rhBMP-2 released initially rapidly, then slowly and constantly. Released rhBMP-2 totaled 23.02 ± 1.03% and 24.69 ± 1.14% in the scaffold-loaded and implant-loaded groups, respectively. There were no significant differences in histologic bone-implant contact (%). Peri-implant bone density (%) was significantly higher in the Scaffold/rhBMP-2(30 µg) and Implant/rhBMP-2(30 µg) groups. Total bone density (%) was not significantly different between the Scaffold/rhBMP-2(5 µg), Implant/rhBMP-2(5 µg), and control groups, or between the Scaffold/rhBMP-2(30 µg) and Implant/rhBMP-2(30 µg) groups, but was significantly higher in the Scaffold/rhBMP-2(30 µg) and Implant/rhBMP-2(30 µg) groups than in the controls. Three-dimensional printed PCL composite scaffold with rhBMP-2 produced vertical osteogenesis and osseointegration, regardless of rhBMP-2 loading to the PCL composite scaffold or implant surface.

Chemical reconstruction of skin scars (CROSS) method for atrophic scars: A comprehensive review.

BACKGROUND: Chemical reconstruction of skin scars (CROSS) applies a high strength acid focally to treat atrophic scars. Although this method has gained popularity over the past two decades, no standardized treatment guideline exists for CROSS method in the treatment of atrophic scars. AIMS: The purpose of this comprehensive review was to evaluate the indications, detailed techniques, efficacy, and safety of CROSS method. MATERIALS AND METHODS: An extensive literature review was conducted to identify articles relating to CROSS method for atrophic scars from 2002 to 2018. RESULTS: The literature search yielded 19 articles meeting criteria. CROSS method has been used for the treatment of acne scars, varicella scars, enlarged pores, and depressed surgical scars. In studies using the quantile grading scale for acne scars, 60%-100% of patients showed >25% improvement. In two studies for varicella scars, 83%-100% of patients showed >25% improvement. CROSS method seems to be effective specifically for ice-pick scars. It is well tolerated and safe in Fitzpatrick skin phototypes I-V. Most reported complications are temporary and include postinflammatory dyspigmentation, erythema, pain, pruritus, infection, and widening of scars. CONCLUSION: This literature review suggests that CROSS method is a safe and effective treatment for atrophic scars, especially ice-pick scars, in skin types I-V. However, current published works have several limitations, including small sample sizes, lack of control group, different concentrations of acid, different frequency of treatments, and follow-up periods. Larger, randomized, controlled studies are needed to elucidate the optimal treatment protocol of CROSS method.

Enhancement of Bone Ingrowth into a Porous Titanium Structure to Improve Osseointegration of Dental Implants: A Pilot Study in the Canine Model.

A porous titanium structure was suggested to improve implant stability in the early healing period or in poor bone quality. This study investigated the effect of a porous structure on the osseointegration of dental implants. A total of 28 implants (14 implants in each group) were placed in the posterior mandibles of four beagle dogs at 3 months after extraction. The control group included machined surface implants with an external implant-abutment connection, whereas test group implants had a porous titanium structure added to the apical portion. Resonance frequency analysis (RFA); removal torque values (RTV); and surface topographic and histometric parameters including bone-to-implant contact length and ratio, inter-thread bone area and ratio in total, and the coronal and apical parts of the implants were measured after 4 weeks of healing. RTV showed a significant difference between the groups after 4 weeks of healing (p = 0.032), whereas no difference was observed in RFA. In the test group, surface topography showed bone tissue integrated into the porous structures. In the apical part of the test group, all the histometric parameters exhibited significant increases compared to the control group. Within the limitations of this study, enhanced bone growth into the porous structure was achieved, which consequently improved osseointegration of the implant.

Surface engineering of titanium alloy using metal-polyphenol network coating with magnesium ions for improved osseointegration.

Although titanium-based implants are widely used in orthopedic and dental clinics, improved osseointegration at the bone-implant interface is still required. In this study, we developed a titanium alloy (Ti-6Al-4V, Ti) coated with epigallocatechin gallate (EGCG) and magnesium ions (Mg2+) in a metal-polyphenol network (MPN) formation. Specifically, Ti discs were coated with EGCG in MgCl2 by controlling their concentrations and pH, with the amount of coating increasing with the coating time. An in vitro culture of human adipose-derived stem cells (hADSCs) on the EGCG-Mg2+-coated Ti showed significantly enhanced ALP activity and mRNA expression of osteogenic markers. In addition, the EGCG-Mg2+-coated Ti enhanced the mineralization of hADSCs, significantly increasing the calcium content (22.2 ± 5.0 µg) compared with cells grown on Ti (13.5 ± 0.3 µg). Treatment with 2-APB, an inhibitor of Mg2+ signaling, confirmed that the enhancement of osteogenic differentiation in the hADSCs was caused by the synergistic influence of EGCG and Mg2+. The EGCG-Mg2+ coating significantly reduced the osteoclastic maturation of Raw264.7 cells, reducing tartrate-resistant acid phosphatase activity (5.4 ± 0.4) compared with that of cells grown on Ti (1.0 ± 0.5). When we placed Ti implants onto rabbit tibias, the bone-implant contact (%) was greater on the EGCG-Mg2+-coated Ti implants (8.1 ± 4.3) than on the uncoated implants (4.4 ± 2.0). Therefore, our MPN coating could be a reliable surface modification for orthopedic implants to enable the delivery of an osteoinductive metal ion (Mg2+) with the synergistic benefits of a polyphenol (EGCG).

Minimally Invasive Procedures for Gender Affirmation.

Despite an increase in the visibility of the transgender population, those who transition continue to face barriers to receiving care through traditional medical providers. Dermatologists can play an important role in the care of transgender patients, through increased understanding and awareness, better outreach, modified medical forms, improved office procedures, and safer and immediately available minimally invasive aesthetic treatments. Minimally invasive aesthetic enhancements that help align appearance with aesthetic goals and gender identity can enhance confidence and improve quality of life. This article discusses gender transition, applicable minimally invasive procedures for the face and body, and illustrative case examples.

Comparative preclinical assessment of the use of dehydrated human amnion/chorion membrane to repair perforated sinus membranes.

PURPOSE: The aim of this study was to evaluate the use of dehydrated human amnion/chorion membrane (dHACM) to repair perforated sinus membranes in rabbits. METHODS: Bilateral surgical windows (7.5-mm diameter) were prepared on the nasal bones of 14 rabbits. Standardized circular perforations (5-mm diameter) were made in the sinus membrane by manipulating implant twist drills. The perforated sinus membranes were repaired using dHACM or a resorbable collagen membrane (CM). The negative control (NC) group did not undergo perforated sinus membrane repair, while the positive control (PC) group underwent sinus augmentation without perforations. The same amount of deproteinized porcine bone mineral was grafted in all 4 groups. After 6 weeks, micro-computed tomography (micro-CT) and histomorphometric evaluations were conducted. RESULTS: The micro-CT analysis revealed that the total augmented volume was not significantly different among the groups. In the dHACM group, newly formed bone filled the augmented area with remaining biomaterials; however, non-ciliated flat epithelium and inflammatory cells were observed on the healed sinus membrane. Histometric analysis showed that the percentage of newly formed bone area in the dHACM group did not differ significantly from that in the CM group. The dHACM group showed a significantly higher percentage of newly formed bone area than the NC group, but there was no significant difference between the dHACM and PC groups. CONCLUSIONS: dHACM could be a feasible solution for repairing sinus membrane perforations that occur during sinus floor augmentation.

Patient satisfaction and our clinical experience with 459 microfocused ultrasound treatments.

PURPOSE: Microfocused ultrasound (MFUS) is a safe and effective method for noninvasive skin tightening. Previous clinical studies demonstrate a 60-100% patient satisfaction after MFUS. We used an anonymous online platform after MFUS to assess patient satisfaction. DESIGN: Patients treated with MFUS between January 2013 and 2016 were invited to complete an anonymous online survey at least 4 months post-treatment. Patients were asked to rate improvement in skin tightening as none (0%), mild (0-25%), moderate (26-50%), significant (51-75%), or dramatic (76-100%) and treatment satisfaction as disappointed, neutral, satisfied, or extremely satisfied. SUMMARY: Between January 2013 and 2016, 253 patients received 459 MFUS treatments at our center. A total of 83 surveys were received with data. Nearly 80% of responders reported at least mild improvement, with 14.5% indicating significant improvement, 27.7% indicating moderate, 37.3% indicating mild, and 20.5% indicating none. In addition, 53.1% of responders reported being satisfied or extremely satisfied with the results. 44.6% of responders did not feel treatment results met expectations. CONCLUSION: Patient satisfaction with elective cosmetic procedures is an important indicator of success. Our current study demonstrates a high response rate, with almost 80% of responders indicating at least mild tightening with MFUS treatment. Interestingly, only 53.1% of patients reported satisfaction after treatment, a lower satisfaction rate than reported in previous non-anonymous studies and lower than patients report in our office follow-up appointments. This discrepancy may be due to gratitude bias. Anonymous surveys likely provide a more accurate assessment of patients' perceptions and will improve physician's future counseling efforts. Lasers Surg. Med. 51:495-499, 2019. © 2019 Wiley Periodicals, Inc.

A Comparative Split-Face Trial of Plant-Based Hypoallergenic Ointment vs Petroleum-Based Ointment Following Fractionated Carbon Dioxide Laser Resurfacing of the Face

Purpose: Fractionated carbon dioxide (CO2) laser resurfacing uses fractional photothermolysis with an ablative 10,600-nm wavelength for treatment of rhytides and photodamage. Although associated with reduced side effect profile from traditional ablative lasers, fractionated lasers can lead to significant erythema, edema, crusting, and exudation for 14 days. Post-care includes regular distilled water soaks and healing ointment. This study evaluated efficacy and patient satisfaction of a novel plant-based hypoallergenic ointment (Doctor Rogers RESTORE®Healing Balm; Product 1) compared to petroleum-based lanolin-containing ointment (Aquaphor® Healing Ointment; Product 2) to accelerate wound healing post-laser resurfacing of the face. Design: This was a single-center, prospective randomized, double-blinded, split-face comparative study of 10 subjects with photo-aging and rhytids who received treatment with fractionated CO2 laser between September 2017 and January 2018. Product 1 and Product 2 were randomized to each half of the face and applied from days 0 to 7 with an option to continue to day 14. The primary outcome measures were Investigator-rated degree of erythema, edema, crusting, exudation, and percentage healing, with follow-up evaluations performed at days 2, 4, 7, 14, and 30. The secondary outcome measure was patient satisfaction. Summary: Based on investigator post-resurfacing scores, day 4 showed improved erythema (50%), edema (50%), crusting (40%), and percentage healing (60%) on the Product 1-treated side compared to Product 2, with the majority of remaining patients scoring the same as Product 2. On day 14, Product 1 demonstrated improvement in erythema (50%), edema (30%), and percentage healing (30%) compared to Product 2, with all remaining patients scoring the same as Product 2. Crusting was the same between the two products on day 14. Ninety percent of patients preferred Product 1 over Product 2, found it easier to use, and were more likely to use it in the future. Conclusion: Product 1 is a plant-based hypoallergenic ointment that is safe and effective post-laser treatment and is associated with high patient satisfaction and preference.

Epidermotropic cutaneous metastases of squamous cell carcinoma from primary esophageal cancer: report of a case and review of the literature.

Metastatic squamous cell carcinoma (SCC) to the skin can be distinguished histologically from primary cutaneous squamous cell carcinoma as, unlike the latter, it is typically separated from the normal overlying squamous epithelium. Rare cases have been reported of cutaneous metastases of SCC that demonstrate continuity with the overlying benign squamous epithelium, termed "epidermotropic cutaneous metastases of SCC." We report the first case of epidermotropic cutaneous metastases of SCC originating from primary esophageal SCC with a review of the literature on this rare histological phenomenon.

Treatment of post-pulsed dye laser purpura with pulsed dye laser.

The pulsed dye laser (PDL) is used for the treatment of a variety of vascular and nonvascular disorders, and its therapeutic efficacy often depends on purpura as an endpoint. However, post-PDL purpura is an undesirable side effect of treatment as it may increase patient dissatisfaction and downtime. Recent studies have suggested that repeat treatment with PDL may speed the resolution of post-procedural purpura; however, there is paucity of data on using repeat PDL treatment specifically for post-PDL purpura. We report three cases of 585 nm PDL-induced purpura treated with 595 nm PDL with clinically significant improvement. We suggest that treatment with PDL, which targets hemoglobin and its breakdown products, after initial PDL treatment may reduce post-PDL purpura.

Effect of microthreads on coronal bone healing of narrow-diameter implants with reverse-tapered design in beagle dogs.

OBJECTIVES: The objective of this study was to investigate the effect of microthreads on the coronal bone healing of narrow-diameter implants with reverse-tapered design. MATERIAL AND METHODS: A total of 52 implants were classified into two groups according to presence or absence of coronal microthreads, the reverse-tapered narrow-diameter implant (RTN) group, and the reverse-tapered narrow-diameter implant with microthreads (RTNM) group. The implants were installed in split-mouth design in the edentulous mandible of six dogs. Three animals were sacrificed at 4 weeks and three at 8 weeks. Resonance frequency analysis, bone measurement using microcomputed tomography (micro-CT), removal torque test, and histometric analysis were performed. RESULTS: No significant differences in implant stability quotient value were observed between the groups at baseline, 4 weeks, or 8 weeks. Bone measurement using micro-CT showed that bone-implant contact volume (BICV) and bone-implant contact volume ratio (BICVR) in the coronal part of RTNM were statistically higher than those in RTN at 4 and 8 weeks. Histometric analysis showed statistically higher bone-implant contact length (BICL) in the coronal part of RTNM than in RTN at 4 weeks; however, bone-implant contact ratio (BICR) was not significantly different between the groups. At 8 weeks, the BICL and BICR did not differ significantly between the groups. Removal torque test showed no significant differences between the groups at 4 and 8 weeks. CONCLUSIONS: The microthreads might facilitate more coronal bone-implant contact due to increased surface areas at an early healing phase; however, they did not significantly affect coronal bone healing at 8 weeks.

Evidence for Anti-Aging South Korean Cosmeceuticals.

As the market for South Korean skin care products grows in the U.S. and worldwide, consumers will increasingly seek advice from dermatologists regarding their efficacy. In this paper, the evidence behind the anti-aging and skin whitening activity of ingredients in the most popular South Korean skin care products was reviewed and critically evaluated. Industry profit data from Euromonitor was obtained to identify the top cosmeceutical brands by retail value in South Korea. The top selling products and their ingredients were then identified from individual brand websites. A comprehensive literature search was conducted using Pubmed to identify and grade the anti-aging and whitening efficacy for nine popular ingredients: licorice, niacinamide, beta-glucan, snail mucus, ginkgo biloba, ginseng, green tea, pomegranate, and soy. Of the various ingredients reviewed, niacinamide, green tea, licorice, and soy have the most published data for anti-aging and whitening activity. Although the literature shows modest results, small sample sizes limit interpretation. High-level evidence to support the use of South Korean skin care products in anti-aging and skin whitening is lacking.

J Drugs Dermatol. 2017;16(4):358-364.

Evaluation of a Reverse-Tapered Design on the Osseointegration of Narrow-Diameter Implants in Beagle Dogs: A Pilot Study.

PURPOSE: The purpose of this study was to evaluate a reverse-tapered design on the osseointegration of narrow-diameter implants in comparison with a conventional tapered design in beagle dogs. MATERIALS AND METHODS: All mandibular premolars and first molars were extracted bilaterally in four beagle dogs. Three months later, three kinds of implants were placed in both quadrants of the mandible: tapered narrow-diameter implants processed by cold working (TNC; n = 8), reverse-tapered narrow-diameter implants (RTN; n = 8), and reverse-tapered narrow-diameter implants processed by cold working (RTNC; n = 8). The animals were sacrificed at 4 weeks. Implant stability quotient (ISQ) values were measured at the time of implant placement and sacrifice. Histomorphometric analysis was performed. RESULTS: The baseline ISQ values were significantly lower in the RTN (56.0 ± 11.6) and RTNC (57.2 ± 9.8) than in the TNC (68.0 ± 5.4; P = .021). At 4 weeks, the TNC (69.9 ± 5.1) exhibited significantly higher ISQ values compared with the RTNC (61.6 ± 4.1; P = .024). Histologic analysis in the RTN and RTNC revealed osseointegration without any signs of inflammation; however, unresolved coronal gap or dehiscence was also observed. The total bone-to-implant contact ratios (BIC) in TNC, RTN, and RTNC were 55.1% ± 11.5%, 47.8% ± 19.1%, and 60.2% ± 15.3%, respectively, and no significant differences were shown among them. The BIC for the coronal part in each group was 51.1% ± 29.4%, 28.8% ± 33.8%, and 23.9% ± 23.3%, respectively, and the differences were not significant. In the threaded part, TNC, RTN, and RTNC showed a BIC of 56.3% ± 9.6%, 50.7% ± 18.3%, and 65.3% ± 15.6%, respectively. There was no significant difference among them. CONCLUSION: The reverse-tapered design on narrow-diameter implants showed a lower initial stability than the conventional tapered design; however, there was equivalent osseointegration in an early healing phase.

Coagulation disorders and their cutaneous presentations: Pathophysiology.

Hypercoagulable states are inherited or acquired predispositions to venous or arterial thromboses that are best understood in the context of the coagulation cascade. Dermatologists can play a critical role in diagnosing and treating patients with hypercoagulable states because cutaneous symptoms may be a presenting manifestation, thereby reducing morbidity and mortality related to these conditions. This review focuses on the epidemiology and pathophysiology of hypercoagulable states, while the accompanying article iterates the basic clinical features, diagnostic testing, and management of patients who have these conditions.

Coagulation disorders and their cutaneous presentations: Diagnostic work-up and treatment.

Both inherited and acquired hypercoagulable states can present with nonspecific clinical manifestations, such as petechiae, purpura, livedo reticularis, and ulcerations. A good history and physical examination are crucial to diagnoses of these conditions. Inherited conditions tend to present either in neonatal period or later in life, while acquired conditions typically occur later in life. Diagnostic studies are performed to identify the coagulation cascade deficiency or defect. Treatment primarily hinges on anticoagulation and wound care. In this article, we provide an in-depth analysis of the clinical manifestations, diagnostic considerations, and management options of patients in hypercoagulable states.

Rare angioinvasive fungal infection in association with leukemia cutis.

Leukemia cutis (LC) is characterized by the infiltration of malignant neoplastic leukocytes or their precursors into the skin and is most often seen in conjunction with systemic leukemia. Patients with LC frequently are in a relative or absolute immunocompromised state. We report the case of a 52-year-old man with primary refractory acute myelogenous leukemia (AML) following allogeneic stem cell transplant (SCT) who presented with a progressive reddish purple nodule with surrounding erythema and central necrosis in the setting of leukocytosis and possible fungal pneumonia. Histopathologic examination revealed an ulcerated dense diffuse dermal infiltrate of large atypical lymphocytes consistent with LC and septate hyphae with acute-angle branching in the dermal blood vessels. Cultures from a biopsied lesion grew Paecilomyces species, a rare but emerging opportunistic infection, despite the patient being on antifungal prophylaxis. This novel report of a rare angioinvasive infection occurring within a lesion of LC supports the need to maintain a high index of suspicion for invasive infection in patients with hematologic malignancy, even those on antifungal prophylaxis.

Comparison of collagen membrane and bone substitute as a carrier for rhBMP-2 in lateral onlay graft.

OBJECTIVES: To evaluate the bone regenerative effect of bioresorbable collagen membrane (CM) as a carrier for recombinant human bone morphogenetic protein-2 (rhBMP-2) when performing lateral onlay grafts using bovine hydroxyapatite incorporated with collagen matrix (BHC) in combination with CM in dogs. MATERIAL AND METHODS: A guided bone regeneration (GBR) was performed at the buccal aspect of edentulous maxillary alveolar ridges in dogs (n = 5): (1) BHC group, in which rhBMP-2-loaded BHC was covered by a CM, and (2) CM group, in which BHC was covered by an rhBMP-2-loaded CM. A histologic and histometric analysis was performed after 8 weeks of healing. RESULTS: Both the BHC and CM groups exhibited substantial newly formed bone (NB). More NB was found in the CM group than in the BHC group without statistical significance. Most of the NB was in direct contact with the residual bone substitute in the BHC group, whereas the projections and islands of NB were observed in the spaces between the residual bone substitute clusters in the CM group. The bone-to-residual bone substitute contact ratio was significantly lower in the CM group than in the BHC group (P = 0.043). CONCLUSIONS: Within the limitations of this study, it can be concluded that rhBMP-2-loaded CM performed lateral onlay grafts as effectively as rhBMP-2-loaded BHC while showing less bone-residual bone substitute contact ratio in dogs. The loading of CMs with rhBMP-2 might therefore be a recommendable treatment option for facilitating lateral onlay graft combined with rhBMP-2.

Combined autophagy and proteasome inhibition: a phase 1 trial of hydroxychloroquine and bortezomib in patients with relapsed/refractory myeloma.

The efficacy of proteasome inhibition for myeloma is limited by therapeutic resistance, which may be mediated by activation of the autophagy pathway as an alternative mechanism of protein degradation. Preclinical studies demonstrate that autophagy inhibition with hydroxychloroquine augments the antimyeloma efficacy of the proteasome inhibitor bortezomib. We conducted a phase I trial combining bortezomib and hydroxychloroquine for relapsed or refractory myeloma. We enrolled 25 patients, including 11 (44%) refractory to prior bortezomib. No protocol-defined dose-limiting toxicities occurred, and we identified a recommended phase 2 dose of hydroxychloroquine 600 mg twice daily with standard doses of bortezomib, at which we observed dose-related gastrointestinal toxicity and cytopenias. Of 22 patients evaluable for response, 3 (14%) had very good partial responses, 3 (14%) had minor responses, and 10 (45%) had a period of stable disease. Electron micrographs of bone marrow plasma cells collected at baseline, after a hydroxychloroquine run-in, and after combined therapy showed therapy-associated increases in autophagic vacuoles, consistent with the combined effects of increased trafficking of misfolded proteins to autophagic vacuoles and inhibition of their degradative capacity. Combined targeting of proteasomal and autophagic protein degradation using bortezomib and hydroxychloroquine is therefore feasible and a potentially useful strategy for improving outcomes in myeloma therapy.