Reduction in skin and mucosal toxicity with pegylated liposomal doxorubicin utilizing every 2-week dosing.

Four ovarian cancer patients with severe plantar palmar erythrodysesthesia or mucositis precluding further therapy from pegylated liposomal doxorubicin on the standard every 4 week schedule were able to be treated on every 2-week schedule without recurrence of plantar palmar erythrodysesthesia or stomatitis.

Long-term soft tissue outcomes for hydroxyapatite-coated bone-anchored hearing implant surgery.

PURPOSE: To investigate skin-related postoperative outcomes following a tissue preservation technique in percutaneous hydroxyapatite-coated bone-anchored hearing aid (BAHA) abutment implantation. METHODS: A retrospective medical records review of adult patients, who underwent single-stage BAHA implantation between July 2013 and November 2017 at a tertiary centre was conducted. Surgical procedures were performed by a single surgeon using a linear incision soft tissue preservation technique. Patients were reviewed at 1 week, 4 weeks, 3 months, 6 months, and annually postoperatively and soft tissue reactions were graded using Holger's score RESULTS: There were 102 patients included with a slight female preponderance (female:male 56:46). There were 586 follow-up episodes during the study period. From the recorded follow-up episodes, Holger's scores were documented as follows: Holger score 0 (89%); 1 (7%); 2 (2%); 3 (1.9%). Three patients (3%) required peri-abutment soft tissue excision (Holger 3) and insertion of longer abutments. One patient (1%) reported atraumatic implant loss. The BAHA was re-implanted in two patients (2%) due to traumatic dislodgement. There was a statistically significant association (p = 0.009) when the mean time to minor skin complications was compared with mean time to a significant skin reaction. CONCLUSION: Tissue preservation technique is the procedure of choice for BAHA abutment implant surgery. It confers excellent soft tissue outcomes and an excellent implant survival rate.

Preoperative care of Polypoid exposed mucosal template in bladder exstrophy: the role of high-barrier plastic wraps in reducing inflammation and polyp size.

OBJECTIVE: To assess the role of high-barrier plastic wrap in reducing the number and size of polyps, as well as decreasing the inflammation and allergic reactions in exstrophy cases, and to compare the results with the application of low-barrier wrap. MATERIALS AND METHODS: Eight patients with bladder exstrophy-epispadias complex (BEEC) that had used a low density polyethylene (LDPE) wrap for coverage of the exposed polypoid bladder in preoperative care management were referred. The main complaint of their parents was increase in size and number of polyps. After a period of 2 months using the same wrap and observing the increasing pattern in size of polyps, these patients were recommended to use a high-barrier wrap which is made of polyvinylidene chloride (PVdC), until closure. Patients were monitored for the number and size of polyps before and after the change of barriers. The incidence of para-exstrophy skin infection/inflammation and skin allergy were assessed. Biopsies were taken from the polyps to identify histopathological characteristics of the exposed polyps. RESULTS: The high barrier wrap was applied for a mean ± SD duration of 12±2.1 months. Polyps' size and number decreased after 12 months. No allergic reaction was detected in patients after the usage of PVdC; three patients suffered from low-grade skin allergy when LDPE was applied. Also, pre-malignant changes were observed in none of the patients in histopathological examination after the application of PVdC. CONCLUSION: Polyps' size and number and skin allergy may significantly decrease with the use of a high-barrier wrap. Certain PVdC wraps with more integrity and less evaporative permeability may be more "exstrophy-friendly".

Bioinspired Functionalized Melanin Nanovariants with a Range of Properties Provide Effective Color Matched Photoprotection in Skin.

Melanin and related polydopamine hold great promise; however, restricted fine-tunabilility limits their usefulness in biocompatible applications. In the present study, by taking a biomimetic approach, we synthesize peptide-derived melanin with a range of physicochemical properties. Characterization of these melanin polymers indicates that they exist as nanorange materials with distinct size distribution, shapes, and surface charges. These variants demonstrate similar absorption spectra but have different optical properties that correlate with particle size. Our approach enables incorporation of chemical groups to create functionalized polyvalent organic nanomaterials and enables customization of melanin. Further, we establish that these synthetic variants are efficiently taken up by the skin keratinocytes, display appreciable photoprotection with minimal cytotoxicity, and thereby function as effective color matched photoprotective agents. In effect we demonstrate that an array of functionalized melanins with distinct properties could be synthesized using bioinspired green chemistry, and these are of immense utility in generating customized melanin/polydopamine like materials.

Comparing ostomates' perceptions of hydrocolloid and silicone seals: a survey.

Most stoma flanges are made of hydrocolloid material. Hydrocolloid is a hydrophilic material that attracts water, potentially resulting in moisture becoming trapped between the flange and skin. Also, as hydrocolloids are absorbent, the material breaks down over time, and there is a risk that some of the adhesive can remain on the skin on removal. Unlike hydrocolloids, silicone comprises fully cross-linked silicone polymers whose properties have been engineered to manage moisture without breaking down (i.e. manage the transepidermal water loss (TEWL)). A questionnaire survey was undertaken to determine ostomates' perceptions of silicone versus hydrocolloid stoma care products (both flanges and seals). The survey was sent to 229 ostomates who had used silicone seals, of whom 78 returned it (a response rate of 34%). The results suggest that use of the silicone seals resulted in a improvement in the condition of the peristomal skin condition, reduced leakage and increased wear time. Further research into this area is required.

Liposome, gel and lipogelosome formulations containing sodium hyaluronate.

The moisture-imparting effect of sodium hyaluronate (Na-HA) was investigated in liposome, gel and lipogelosome topical formulations. Sixteen liposome formulations were prepared with or without Na-HA (45 kDa) using various ratios of dimyristoylphosphatidylcholine, 1,2-dimyristoyl-sn-glycero-3-phosphatidylglycerol, dipalmitoylphosphatidylcholine and phospholipon 100H. The liposomes were characterized in terms of their structure, composition, zeta potential, Na-HA-entrapment capacity and stability. In particular, scanning electron microscopy, polarized light microscopy, dynamic light scattering and atomic force microscopy were utilized to probe appearance, size and size distribution and lamellarity. The work was then extended to gels using the gelling agents poloxamer (PXM 188 or 407) and Carbopol or Ultrez 21 (U-21), yielding liposome-loaded gel formulations (i.e. lipogelosomes). The in vitro release kinetics of Na-HA from liposomes, lipogelosomes and commercial Na-HA reference formulations were studied via a flow-through cell method. Among the liposomal formulations tested, L6, comprising of Na-HA-loaded phospholipon 100H:stearylamine:cholesterol (7:1:2), displayed optimal traits. The mean particle size, zeta potential and entrapment capacity of L6 were determined as 1900 nm, -20.9 mV and 15.0%. The optimum lipogelosome, LG4, was obtained by incorporating liposome L6 into a U-21 gel at a ratio of 1:1 (w/w). In clinical trials, in-house formulations were applied twice daily to 15 female volunteers. The two-week benefits were assessed against a commercial product; and in all cases, changes of skin humidity, sebum content, pH and wrinkle depth were promising. In particular, the LG4 lipogelosome-based formulation had significantly improved skin hydration and compliance, as evidenced by a moisture content gain of 30.4%.

Peristomal skin irritation and the use of a silicone-based barrier film.

Maintaining skin integrity is vital to ensure good adhesion of the stoma pouch, and to avoid discomfort for the person with a stoma, ensuring a good quality of life. However, there are many risk factors associated with potential peristomal skin soreness, and a large number of research studies have highlighted the vast number of patients who actually experience these problems (Mahjoubi, 2005; Ratliff et al, 2005; Herlufsen et al, 2006; Lynch et al, 2008; Meisner and Balleby, 2008). Clinical nurse specialists in stoma care are responsible for ensuring that all patients are fully assessed, and also that patients are given appropriate evidence-based care to avoid peristomal skin irritation, where possible. This article will discuss the common causes of peristomal skin breakdown, the tools available to assist with assessment, and how to best treat peristomal skin irritation.

Minimizing adverse events associated with poly-L-lactic acid injection.

BACKGROUND Injectable devices offer an attractive alternative to surgical cosmetic rejuvenation. Many injectable products are biocompatible but demonstrate varying levels of durability, ranging from temporary to permanent. Product duration is determined, in part, by its mode of operation. Passive fillers, such as collagen, generally add volume through mass, whereas other injectables, such as poly-L-latic acid (PLLA), rely on a foreign-body response in which endogenous collagen production by fibroblasts is thought to generate new volume. OBJECTIVE To review the use of injectable PLLA, specifically regarding optimal injection technique that can reduce adverse events (AEs) and enhance out comes. RESULTS PLLA has been used extensively to correct HIV-related facial lipoatrophy, with effects lasting for up to 2 years. The efficacy and safety of PLLA can be influenced by correct product reconstitution, dilution, and administration. Undesired AEs, such as papules and nodules, may result from incorrect reconstitution, uneven product distribution in the suspension, imprecise injection technique (superficial injection), or lack of posttreatment massage. CONCLUSION Administration of PLLA with optimal techniques can help enhance treatment effect while simultaneously minimizing AES.

Engineered nanoparticles bind elapid snake venom toxins and inhibit venom-induced dermonecrosis.

Envenomings by snakebites constitute a serious and challenging global health issue. The mainstay in the therapy of snakebite envenomings is the parenteral administration of animal-derived antivenoms. Significantly, antivenoms are only partially effective in the control of local tissue damage. A novel approach to mitigate the progression of local tissue damage that could complement the antivenom therapy of envenomings is proposed. We describe an abiotic hydrogel nanoparticle engineered to bind to and modulate the activity of a diverse array of PLA2 and 3FTX isoforms found in Elapidae snake venoms. These two families of protein toxins share features that are associated with their common (membrane) targets, allowing for nanoparticle sequestration by a mechanism that differs from immunological (epitope) selection. The nanoparticles are non-toxic in mice and inhibit dose-dependently the dermonecrotic activity of Naja nigricollis venom.

2% chlorhexidine-70% isopropyl alcohol versus 10% povidone-iodine for insertion site cleaning before central line insertion in preterm infants: a randomised trial.

OBJECTIVE: To determine whether 2% chlorhexidine gluconate-70% isopropyl alcohol (CHX-IA) is superior to 10% aqueous povidone-iodine (PI) in preventing catheter-related blood stream infection (CR-BSI) when used to clean insertion sites before placing central venous catheters (CVCs) in preterm infants. DESIGN: Randomised controlled trial. SETTING: Two neonatal intensive care units (NICUs). PATIENTS: Infants <31 weeks' gestation who had a CVC inserted. INTERVENTIONS: Insertion site was cleaned with CHX-IA or PI. Caregivers were not masked to group assignment. MAIN OUTCOME MEASURES: Primary outcome was CR-BSI determined by one microbiologist who was masked to group assignment. Secondary outcomes included skin reactions to study solution and thyroid dysfunction. RESULTS: We enrolled 304 infants (CHX-IA 148 vs PI 156) in whom 815 CVCs (CHX-IA 384 vs PI 431) were inserted and remained in situ for 3078 (CHX-IA 1465 vs PI 1613) days. We found no differences between the groups in the proportion of infants with CR-BSI (CHX-IA 7% vs PI 5%, p=0.631), the proportion of CVCs complicated by CR-BSI or the rate of CR-BSI per 1000 catheter days. Skin reaction rates were low (<1% CVC insertion episodes) and not different between the groups. More infants in the PI group had raised thyroid-stimulating hormone levels and were treated with thyroxine (CHX-IA 0% vs PI 5%, p=0.003). CONCLUSIONS: We did not find a difference in the rate of CR-BSI between preterm infants treated with CHX-IA and PI, and more infants treated with PI had thyroid dysfunction. However, our study was not adequately powered to detect a difference in our primary outcome and a larger trial is required to confirm our findings. TRIAL REGISTRATION: This study was registered with the EU clinical trials register before the first patient was enrolled (Eudract 2011-002962-19). (https://www.clinicaltrialsregister.eu).

Percutaneous absorption of aromatic amines in rubber industry workers: impact of impaired skin and skin barrier creams.

BACKGROUND: Several aromatic amines (AA) could cause bladder cancer and are an occupational hygiene problem in the workplace. However, little is known about the percutaneous absorption of chemicals via impaired skin and about the efficacy of skin protection measures to reduce internal exposure. AIMS: To determine the impact of skin status and of skin protection measures on the internal exposure to AA in workers manufacturing rubber products. METHODS: 51 workers occupationally exposed to aniline and o-toluidine were examined. The workplace conditions, risk factors for skin and the use of personal protective equipment were assessed by means of a self-administered questionnaire. The skin of hands and forearms was clinically examined. Exposure to aniline and o-toluidine was assessed by ambient air and biological monitoring (analyses of urine samples and of haemoglobin adducts). RESULTS: Haemoglobin-AA-adduct levels in workers with erythema (73%) were significantly higher (p<0.04) than in workers with healthy skin (mean values: aniline 1150.4 ng/l vs 951.7 ng/l, o-toluidine 417.9 ng/l vs 118.3 ng/l). The multiple linear regression analysis showed that wearing gloves significantly reduced the internal exposure. A frequent use of skin barrier creams leads to a higher internal exposure of AA (p<0.03). However, the use of skincare creams at the workplace was associated with a reduced internal exposure (p<0.03). From these findings we assume that internal exposure of the workers resulted primarily from the percutaneous uptake. CONCLUSIONS: The study demonstrates a significantly higher internal exposure to AA in workers with impaired skin compared with workers with healthy skin. Daily wearing of gloves efficiently reduced internal exposure. However, an increased use of skin barrier creams enhances the percutaneous uptake of AA. Skincare creams seem to support skin regeneration and lead to reduced percutaneous uptake.

Cutaneous adverse effects of the immune checkpoint inhibitors.

The immune checkpoint targeted agents, anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and anti-programed cell death 1 (PD-1) or anti-programmed death ligand 1 (PD-L1) inhibitors are frequently associated with cutaneous side effects that are often dose limiting and can lead to discontinuation of therapy. Ipilimumab, a CTLA-4 inhibitor, is most commonly associated with a morbilliform eruption on the trunk and extremities and pruritus. More severe cutaneous toxicities reported include toxic epidermal necrolysis and severe drug rash with eosinophila and systemic symptoms. Recent case reports of Sweet syndrome and cutaneous sarcoidosis have also recently been described after treatment with ipilimumab. The cutaneous events usually occur early in the course of treatment and are dose dependent. PD-1 inhibitors, nivolumab and pembrolizumab, induce similar but less severe toxicities compared with the CTLA-4 inhibitors. The most common cutaneous adverse events include lichenoid reactions, eczema, vitiligo, and pruritus. Lichenoid oral mucosal lesions located on the tongue, buccal mucosa, lips, or gingivae or located on all of these have also recently been described. The time of onset of the cutaneous events with the PD-1 inhibitors occurs later than that seen with the CTLA-4 inhibitors. Anti-PD-L1 antibodies, such as atezolizumab, have a similar side effect profile compared with the PD-1 inhibitors. Combination of immune checkpoint inhibitors, ipilimumab and nivolumab, has recently been approved for the treatment of advanced melanoma. The combination therapy is associated with a more severe side effect profile compared with the agents used as monotherapy. We discuss the most frequently encountered cutaneous side effects of the immune checkpoint inhibitors and review the recommended management strategies.

Bifunctional viscous nanovesicles co-loaded with resveratrol and gallic acid for skin protection against microbial and oxidative injuries.

Resveratrol and gallic acid were co-loaded in phospholipid vesicles aiming at protecting the skin from external injuries, such as oxidative stress and microbial infections. Liposomes were prepared using biocompatible phospholipids dispersed in water. To improve vesicle stability and applicability, the phospholipids and the phenols were dispersed in water/propylene glycol or water/glycerol, thus obtaining PEVs and glycerosomes, respectively. The vesicles were characterized by size, morphology, physical stability, and their therapeutic efficacy was investigated in vitro. The vesicles were spherical, unilamellar and small in size: liposomes and glycerosomes were around 70nm in diameter, while PEVs were larger (∼170nm). The presence of propylene glycol or glycerol increased the viscosity of the vesicle systems, positively affecting their stability. The ability of the vesicles to promote the accumulation of the phenols (especially gallic acid) in the skin was demonstrated, as well as their low toxicity and great ability to protect keratinocytes and fibroblasts from oxidative damage. Additionally, an improvement of the antimicrobial activity of the phenols was shown against different skin pathogens. The co-loading of resveratrol and gallic acid in modified phospholipid vesicles represents an innovative, bifunctional tool for preventing and treating skin affections.

Effects of tea, decaffeinated tea, and caffeine on UVB light-induced complete carcinogenesis in SKH-1 mice: demonstration of caffeine as a biologically important constituent of tea.

Oral administration of green or black tea inhibited UVB light-induced complete carcinogenesis in the skin of SKH-1 mice. Green tea was a more effective inhibitor than black tea. Oral administration of decaffeinated green or black tea resulted in substantially less inhibitory activity than did administration of the regular teas, and in one experiment, administration of a high-dose level of the decaffeinated teas enhanced the tumorigenic effect of UVB. Oral administration of caffeine alone had a substantial inhibitory effect on UVB-induced carcinogenesis, and adding caffeine to the decaffeinated teas restored the inhibitory effects of these teas on UVB-induced carcinogenesis. In additional studies, topical application of a green tea polyphenol fraction after each UVB application inhibited UVB-induced tumorigenesis. The results indicate that caffeine contributes in an important way to the inhibitory effects of green and black tea on UVB-induced complete carcinogenesis.

Dermatologic signs in patients with eating disorders.

Eating disorders are significant causes of morbidity and mortality in adolescent females and young women. They are associated with severe medical and psychological consequences, including death, osteoporosis, growth delay and developmental delay. Dermatologic symptoms are almost always detectable in patients with severe anorexia nervosa (AN) and bulimia nervosa (BN), and awareness of these may help in the early diagnosis of hidden AN or BN. Cutaneous manifestations are the expression of the medical consequences of starvation, vomiting, abuse of drugs (such as laxatives and diuretics), and of psychiatric morbidity. These manifestations include xerosis, lanugo-like body hair, telogen effluvium, carotenoderma, acne, hyperpigmentation, seborrheic dermatitis, acrocyanosis, perniosis, petechiae, livedo reticularis, interdigital intertrigo, paronychia, generalized pruritus, acquired striae distensae, slower wound healing, prurigo pigmentosa, edema, linear erythema craquele, acral coldness, pellagra, scurvy, and acrodermatitis enteropathica. The most characteristic cutaneous sign of vomiting is Russell's sign (knuckle calluses). Symptoms arising from laxative or diuretic abuse include adverse reactions to drugs. Symptoms arising from psychiatric morbidity (artefacta) include the consequences of self-induced trauma. The role of the dermatologist in the management of eating disorders is to make an early diagnosis of the 'hidden' signs of these disorders in patients who tend to minimize or deny their disorder, and to avoid over-treatment of conditions which are overemphasized by patients' distorted perception of skin appearance. Even though skin signs of eating disorders improve with weight gain, the dermatologist will be asked to treat the dermatological conditions mentioned above. Xerosis improves with moisturizing ointments and humidification of the environment. Acne may be treated with topical benzoyl peroxide, antibacterials or azaleic acid; these agents may be administered as monotherapy or in combinations. Combination antibacterials, such as erythromycin with zinc, are also recommended because of the possibility of zinc deficiency in patients with eating disorders. The antiandrogen cyproterone acetate combined with 35 microg ethinyl estradiol may improve acne in women with AN and should be given for 2-4 months. Cheilitis, angular stomatitis, and nail fragility appear to respond to topical tocopherol (vitamin E). Russell's sign may decrease in size following applications of ointments that contain urea. Regular dental treatment is required to avoid tooth loss.

Evaluation of protective ointments used against dermal effects of nitrogen mustard, a vesicant warfare agent.

Mustard, a vesicant warfare agent, has cytotoxic, mutagenic, and cytostatic effects via alkylation of DNA and inhibition of DNA replication. Since symptoms appear following a latent period, it can cause some subacute and chronic effects to occur and delay in the treatment. Therefore, the main approach should be the use of protective preparation to reduce the skin toxicity. Thus, this study was conducted in guinea pigs (350-400 g) shaved in areas of 10 x 10 cm. Mechlorethamine HCl (100 mg), a nitrogen mustard derivative, in ethanol was applied by spraying on hairless regions where previously prepared pharmaceutical topical formulations were medicated before. The experimental regions of the animals were kept preserved from environmental factors. Forty-eight hours after the application of the protective ointments and mechlorethamine consecutively, skin-damaging effects were macroscopically evaluated in terms of erythema formation, ulceration, necrosis, and inflammation occurrences. Then, punch biopsy was performed from these damaged sites for histopathological evaluation. Although numerous topical formulations were prepared and tested for protection, according to microscopic examination of the pathologic sections, tissue specimen treated with the ointment containing the mixture of zinc oxide, zinc chloride, dimethylpolysiloxane in a base of petroleum jelly was determined as being the most effective protective against skin injury caused by the vesicant agent.

[Epidermal growth factor, innovation and safety]. / Factor de crecimiento epidérmico, innovación y seguridad.

Bioidentical recombinant human epidermal growth factor (rhEGF) is available in concentrations and purity suitable for therapeutic use in long time stable formulations. Beneficial effects in several skin pathologies and lesions have been reported (traumatic and surgical wound healing, laser induced wounds, abnormal scars, keloids, radiation or chemotherapy induced dermatitis, post inflammatory hyperpigmentation or for skin aging damage repairing) and also may be considered for the treatment of several oropharingeal and high gastroesophageal tract mucosa diseases (mouth sores, pharyngeal fistulas, ulcers), and several corneal or conjunctive mucosa lesions. rhEGF has not shown any important side or collateral effects in humans or in laboratory experimentation animals, showing optimal tolerability and safety with continuous use for months. Compounding gives advantages of versatility, individualization, personalization, molecular stability, safety and effectiveness in ideal conditions, showing good tissue penetration, both on intact skin and skin lesions that expose the lower planes to the surface. rhEGF compounds can be considered for prevention or as a treatment of diverse skin and mucosa diseases and conditions through compounding preparations.

Promoting sun awareness: evaluation of an educational children's book.

OBJECTIVE: To assess the value of early childhood education as a means of increasing awareness and knowledge about the sun and related skin disease(s). METHODS: A children's book promoting sun awareness and protection was developed. The next was incorporated into the health education curriculum of two third-grade classrooms (n = 82). The students completed a questionnaire before, immediately after, and 6 weeks after reading the text. Student sun awareness knowledge was compared using descriptive statistics and paired T-tests. RESULTS: Behaviors and attitudes that resulted in over-exposure to the sun's ultraviolet light were common among third-graders. Primary test areas included the sun's effect on skin, effective sunscreens, skin type, and skin cancer. Test scores showed a marked improvement (40% compared with baseline) in knowledge of sun protection at both posttests. Parents represented the greatest source of information for children (28 of 82) before this study, while doctors and teachers each accounted for only 1 of 82. CONCLUSIONS: Preventive measures in childhood have the potential to significantly reduce the incidence of sunrelated skin diseases; however, education to date has been directed primarily at presents. This study demonstrated that an educational book for elementary school students can be an effective tool to increase sun awareness and knowledge. The multifaceted approach to prevention recommended here is similar to that of the highly successful dental care campaign, consisting of direct education of children by physicians, teachers, parents, and the media.

Green tea and skin.

OBJECTIVE: To discuss the current knowledge of polyphenolic compounds present in green tea as anti-inflammatory, antioxidant, and anticarcinogenic in skin. DATA SOURCES: References identified from bibliographies of pertinent articles, including our work in related fields. STUDY SELECTION AND DATA EXTRACTION: Articles were selected based on the use of green tea or its polyphenolic constituents for prevention against inflammation and cancer in the skin. Also discussed is the possible use of green tea to treat various inflammatory dermatoses. DATA SYNTHESIS: The polyphenolic compounds from green tea were tested against chemical carcinogenesis and photocarcinogenesis in murine skin. These green tea polyphenols were found to afford protection against chemical carcinogenesis as well as photocarcinogenesis in mouse skin. A few experimental studies were conducted in human skin in our laboratory. Analysis of published studies demonstrates that green tea polyphenols have anti-inflammatory and anticarcinogenic properties. These effects appear to correlate with antioxidant properties of green tea polyphenols. CONCLUSIONS: The outcome of the several experimental studies suggests that green tea possess anti-inflammatory and anticarcinogenic potential, which can be exploited against a variety of skin disorders. Although more clinical studies are needed, supplementation of skin care products with green tea may have a profound impact on various skin disorders in the years to come. Arch Dermatol. 2000;136:989-994