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Background Ferula persica is one of the most important traditional medicinal plants that is used to treat various diseases such as diabetes, backache and rheumatism. The aim of the present study was to evaluate the anti‐inflammatory and wound healing potential of F. persica using stereological and molecular methods in experimental models. Methods In the present study, two wound models (circular excision and linear incision) were used. Male Wistar rats were divided into four groups (n = 16), including control, vehicle treated, treated with F. persica extract ointment (5% w/w) and treated with the reference drug (Madecassol). All the animals were treated topically once a day. The circular and linear wounds were treated for 9 and 17 days, respectively. At the end of the study, samples from wounds area were harvested for histology, stereology, immunohistochemistry and molecular assessments to determine the in vivo healing potential and anti‐inflammatory activity. Results We observed significant recovery in macroscopic evaluation of wound healing in the F. persica extract treated group compared with the control and vehicle treated groups (p 0.05, p, Stereological and molecular studies on the effects of Ferula persica extract on wound healing in rats.

Background Wound management is a critical factor when treating patients with the inherited skin fragility disease dystrophic epidermolysis bullosa (DEB). Due to genetic defects in structural proteins, skin and mucous epithelia are prone to blistering and chronic wounding upon minor trauma. Furthermore, these wounds are commonly associated with excessive pruritus and predispose to the development of life-threatening squamous cell carcinomas, underscoring the unmet need for new therapeutic options to improve wound healing in this patient cohort. Vitamin D3 is acknowledged to play an important role in wound healing by modulating different cellular processes that impact epidermal homeostasis and immune responses. In this study, we evaluate the safety and efficacy of low-dose calcipotriol, a vitamin D3 analogue, in promoting wound healing and reducing itch and pain in patients with DEB. Methods Eligible DEB patients, aged ≥ 6 years and with a known mutation in the COL7A1 gene, were recruited to a placebo-controlled, randomized, double blind, cross-over phase II monocentric clinical trial. Patients were required to have at least two wounds with a minimum size of 6 cm2 per wound. The primary objective was to evaluate efficacy of daily topical application of a 0.05 µg/g calcipotriol ointment in reducing wound size within a 4-week treatment regimen. Secondary objectives were to assess safety, as well as the impact of treatment on pruritus, pain, and bacterial wound colonization in these patients. Results Six patients completed the clinical trial and were included into the final analysis. Topical low-dose calcipotriol treatment led to a significant reduction in wound area at day 14 compared to placebo (88.4% vs. 65.5%, P P 0.05) and 1.83 vs 5.52 (P 0.0001) at days 14 and 28, respectively. Treatment with low-dose calcipotriol did not affect serum calcium levels and improved the species richness of the wound microbiome, albeit with no statistical significance. Conclusions Our results show that topical treatment with low-dose calcipotriol can accelerate wound closure and significantly reduces itch, and can be considered a safe and readily-available option to improve local wound care in DEB patients. TrialRegistration EudraCT: 2016–001,967-35. Registered 28 June 2016, https://www.clinicaltrialsregister.eu/ctr-search/trial/2016-001967-35/AT

Purpose Topical calcineurin inhibitors (TCIs) are an important anti-inflammatory drug for treating atopic dermatitis (AD). However, those treatment responses are variable. In this study, we stratified AD patients by patterns of response to remission maintenance therapy (proactive therapy) with topical tacrolimus, a typical TCI. Thereafter, we explored patient features that predict the success or failure of proactive therapy using TCI (TCI proactive therapy). Methods A single-arm open-label clinical study aimed to evaluate the efficacy of TCI proactive therapy was conducted in 31 patients with AD. Patients were treated with TCS to induce remission (remission-induction period) followed by daily TCI ointment (0.1% tacrolimus) application for 4 weeks (maintenance therapy period), and twice-weekly application for 12 weeks (proactive therapy period). Based on its results, treatment outcomes were correlated with the patients’ clinical and laboratory findings. Results Of the 31 patients enrolled in the study, 21 successfully completed maintenance therapy (TCI responders). Among them, 13 completed (proactive-completed group) and 8 failed proactive therapy (proactive-dropout group). At the beginning of maintenance therapy, the serum IgE level was significantly higher in the TCI responders than in those who failed maintenance therapy (p = 0.049). At the beginning of proactive therapy, the mean-SCORing Atopic Dermatitis (SCORAD) score was significantly different between the proactive-completed (11.7 ± 4.6) and proactive-dropout (16.6 ± 4.2) groups (p = 0.025). In proactive-dropout group patients, worsened disease activity correlated well with the elevation of serum lactate dehydrogenase (LDH) and Thymus and activation-regulated chemokine (TARC) levels and peripheral eosinophil count. Conclusion AD patients were stratified into three different response patterns to TCI proactive therapy. Patients with less involvement of IgE in the pathogenesis and inadequate remission induction by TCS may not be expected to respond well to TCI proactive therapy.Key messagesAD patients can be stratified into three types according to their pattern of responsiveness to TCI proactive therapy.The efficacy of TCI proactive therapy is lower in AD patients with lower serum IgE levels.TCI proactive therapy should be done after the achievement of adequate remission induction by TCS.

Skin graft surgery is a standard treatment that increases the survival rate of patients with burn injuries; however, it leaves many sequelae. Conventional external preparations for the treatment of burns also have various side effects. In this retrospective case study, we assessed the cases of four patients with topical third-degree burns who did not wish to undergo the skin graft surgeries recommended by medical doctors and were thus treated using traditional medicine alone. A Korean medicine doctor administered integrative traditional medicine treatment to the patients using acupuncture and herbal ointments. Analysis of the patients’ treatment photographs, quantitative evaluation indices, and vivid narratives suggested that their skin recovered well without adverse effects. Traditional Korean medicine treatment, including acupuncture and herbal ointment treatment, can be a new alternative therapeutic strategy for the treatment of patients with topical burns who do not want to undergo skin graft surgery or who have higher risks for poor surgical outcomes.

Background Episiotomy is the most commonn surgical procedure in midwifery which as any other wounds can cause infection or delay in healing. The current study aimed to determine effect of Silybum marianum ointment on pain severity and healing of episiotomy wound in primiparous women referring to Shahid Nourani Hospital at 2019. Methods This research was done as a randomized, triple-blind clinical trial on 87 priiparous women (44 indivdiuals in Silybum marianum ointment group and 43 indivdiuals in placebo group) referred to Shahid Nourani Hospital in Talesh (Guilan Province), Iran at September 2019. After labor and performing episiotomy, twice a day for 10 days as a fingertip size of the ointment was prescribed to be topically used on the episiotomy incision for both groups (Silybum marianum ointment or placebo ointment). Data gathering was done using demographic and midwifery information questionnaire, Episiotomy healing assessment: Redness, Edema, Ecchymosis, Discharge, Approximation)REEDA Scale (REEDA Scale: Redness(R); Edema (E), Ecchymosis(E), Discharge from the wound(D); Approximation of the perineal tissues(A))(scale, and visual analogue scale of pain. Examination of healing status of the perinea incision was performed during first 12 h, fifth day and tenth day after labor.Kolmogrov-Smirnov test was used in order to investiagte nomrality of data distribution of quantitative data, and two- independent samples t test, Chi square, repeated measures two factorial analysis of variance and Fischer’s exact test were used. SPSS software version 23 was used to analyze data and 0.05 was considered as signifcance level. Results Both groups of Silybum marianum and placebo groups did not differ regarding demographic and midwifery characteristics, hygiene status prior to intervention (P > 0.05). Mean difference of pain severity and REEDA scale in Silybum marianum ointment group in 12 h after labor, at fifth day and tenth day after labor was significant comparing to control group which indicates decline in episiotomy pain severity and faster wound healing (P Conclusions Silybum marianum ointment ointment accelerates episiotomy wound healing rate due to its healing properties and decreases pain severity. Trial registration This study was registered in Iranian Registry of Clinical Trials in 10/08/2019 with the IRCT ID: IRCT201811100411603N1.

Mucocutaneous infections caused by Herpes simplex virus (HSV-1 and HSV-2) are characterized by the appearance of vesicles that cause pain and embarrassment to the carrier. The standard treatment is based on the use of antivirals in gels or ointments, however, relapses are common. Local anesthetics decrease the pain caused by the lesion, in addition to showing antiviral properties. Semi-solid form facilitates application and its transformation into a thin film favors the maintenance of the formulation in place, with a more discreet final aspect. The objective of this study was to develop and evaluate formulations containing anesthetics for the treatment of cold sores. For this purpose, two semi-solid film-forming formulations were developed and evaluated, containing HPMC K100, lidocaine (LIDO) and prilocaine (PRILO) combined with adjuvants, in the presence (F1T) or not (F1) of the absorption promoter Transcutol®. The mixture of PRILO and LIDO resulted in the formation of a eutectic mixture (EM), essential for penetration of drugs into the skin. The quantification of drugs was performed by HPLC (High Performance Liquid Chromatography), and Transcutol® did not influence the release of drugs from the formulation. The bioadhesiveness of the formulation was evaluate and the drugs did not impair the adhesive potential of the polymers used. The formulations were evaluated in vivo for skin irritation and did not show any negative sign on macroscopic examination. The in vivo efficacy test proved the anesthetics' ability to decrease the lesions caused by HSV-1. Thus, the proposed formulations proved to be good alternatives to the treatment of oral lesions caused by HSV-1.

INTRODUCTION Melasma remains a recurrent, chronic, therapeutically challenging, and psychologically burdening condition. Several different modalities and approaches have been utilized, and some with notable success to experimentally manage the condition. Cysteamines, with their depigmentation properties, have only recently been intensely studied. One such formulation is the topical 5% cysteamine hydrochloride, the structure of which is notably more stable and with a less foul odor than its prior counterparts. We, therefore, aimed to assess the efficacy of the mentioned formulation in the treatment of melasma. METHODS The PubMed, SCOPUS, ISI Web of Science, and Embase, Cochrane, and Proquest databases were thoroughly searched for English studies evaluating the effects of the topical agent mentioned. RESULTS Eight studies (five RCTs, two case reports, and one case series) were included after three rounds of screening, most of which were carried out in Iran. Statistical significance was noted when assessing decreased melanin content and satisfaction rates. CONCLUSIONS It appears that the cysteamine cream could be comparably efficient in treating melasma while accompanied only by minor and transient adverse events. However, current evidence is limited by insufficient sample size, long-term follow-up, and only to epidermal melasma, highlighting the need for appropriately designed randomized controlled clinical trials to draw a conclusive image of the cysteamine's role in treating this recalcitrant condition.

Objective To introduce a new method of treating facial soft tissue defect by observing the clinical curative effects of traditional Chinese medicine moisture exposed burn ointment in treating facial soft tissue defect. Methods A total of 85 patients with facial soft tissue defects were treated with traditional Chinese medicine moisture exposed burn ointment, and the clinical therapeutic effects were analyzed by observing the wound healing time, scar formation and changes of facial appearance and functions. Results Of the 85 patients, the shortest wound healing time was 12 days and the longest was 72 days; the facial appearance and functions restored to be normal in 74 patients, with good skin elasticity and mild scar formation in the wound area; 11 patients were lost to the follow-up; two patients suffered from the longest wound healing time due to their skin defect of nasal tip and nasal columella and the cartilage defect of nasal wings, and V-shaped defects were left at the edge of the left nostrils after the wound healing, which may be attributed to the ineffectiveness of MEBT/MEBO on cartilage. Conclusion Traditional Chinese medicine moisture exposed burn ointment can realize more satisfying healing effects when applied in the treatment of facial soft tissue defects, including user-friendly operation, no special requirements for medical devices, obviously lower treatment cost, etc., and thus it is an easy-to-operate and effective way for such patients, especially for elderly patients, patients with poor body conditions and patients unbearable to undergo complicated operations.

Background: Crisaborole is a nonsteroidal anti-inflammatory phosphodiesterase 4 inhibitor that is approved for the treatment of patients with mild-to-moderate atopic dermatitis (AD); however, the efficacy and safety of crisaborole in patients with AD and other atopic comorbidities have not been investigated. Objective: This post hoc pooled analysis of the pivotal phase III studies (CrisADe CORE 1 and CORE 2) assessed the efficacy and safety of crisaborole versus vehicle in patients aged ≥ 2 years with mild-to-moderate AD and other atopic comorbidities. Methods: Patients with mild-to-moderate AD and a medical history of asthma, allergic rhinitis, or food allergies were identified. Efficacy assessments included the proportion of patients who achieved Investigator's Static Global Assessment (ISGA) success at day 29, ISGA clear or almost clear at day 29, and improvement in the Severity of Pruritus Scale score at week 4. Safety was assessed via treatment-emergent adverse events (TEAEs). Results: This analysis included 1522 patients (crisaborole, 1016; vehicle, 506); 26.2, 15.9, and 16.5% had a medical history of asthma, allergic rhinitis, and food allergies, respectively. The mean age was 12.2 years. A significantly greater proportion of patients treated with crisaborole achieved ISGA success at day 29 compared with patients treated with vehicle for most subgroups analyzed. Furthermore, a significantly greater proportion of patients treated with crisaborole achieved ISGA clear or almost clear at day 29 across all subgroups and demonstrated improvement in the Severity of Pruritus Scale score at week 4 versus patients treated with vehicle in most of the subgroups. Overall, most TEAEs were mild or moderate in severity; the most common treatment-related TEAE in patients with atopic comorbidities was application-site pain (crisaborole, 5.1%; vehicle, 1.7%). Conclusion: Crisaborole was efficacious and well tolerated in patients with mild-to-moderate AD and other atopic comorbidities, which suggested that crisaborole should be considered for the management of AD in this population. Clinical Trials NCT02118766 (CrisADe CORE 1) and NCT02118792 (CrisADe CORE 2), www.clinicaltrials.gov

ReveromycinA (RMA) was developed and is a unique agent for inhibiting osteoclast activity. In a previous study, we experimentally induced periodontal disease in a high-turnover osteoporosis osteoprotegerin-knockout mice (OPG KO) model and found that intraperitoneal administration of RMA inhibited alveolar bone resorption. We prepared a novel RMA-containing ointment for topical non-invasive administration in the oral cavity, in preparation for possible future clinical application. And we investigated whether this ointment can inhibit alveolar bone resorption in an experimental mouse model of periodontal disease. We examined wild-type (WT) and OPG KO mice ligated with wire around contact points on the left first and second molars to cause food impaction and induce experimental periodontal disease. RMA was administered three times a day. Using micro-computed tomography, we measured the volume of alveolar bone loss and also performed histological analysis. Our findings showed that localized administration of RMA containing ointment resulted in suppressed alveolar bone resorption, reduced osteoclast count, and lower immunostaining scores of inflammation sites compared with controls in both OPG KO and WT mice. Localized application of the specific osteoclast suppressor RMA in ointment form in the oral cavity could be a novel treatment for periodontitis that inhibits alveolar bone resorption locally.

We examined whether steroid ointment (0.1% dexamethasone) is an effective treatment for mucoceles.Using a retrospective cohort study design, a statistical study was conducted of 91 patients diagnosed with mucoceles at the Department of Dental and Oral Surgery, Saga University Hospital, Saga, Japan, between January 2006 and December 2016. The patients' age and sex; shape, size, and site of the lesion; duration; and treatment response rate were evaluated.The most frequent site of mucoceles was the lower labial mucosa, and several were10 mm in size. The age of onset was often20 years, with no sex-based differences. The treatment response rate was 65.8% for steroid ointment and 100% for surgical removal. In the subgroup analysis according to each clinical factor, some subgroups showed statistically nonsignificant differences compared with the surgery group. Among them, the older age and short disease duration subgroups showed small risk differences, suggesting that application of ointment may lead to a response in these subgroups.Although its response rate was lower than that of surgical removal, topical steroid application is a noninvasive and useful treatment method that can be used for patients in whom surgical treatment is infeasible.

The treatment of skin burns is one of the most important challenge in medical science. The aim of this study is evaluation of the efficacy of Artaderm herbal ointment containing the Henna (Lawsonia inermis) extract, Linseed (Linum usitatissimum) oil, and Honey Wax on wound healing in the rat with second-degree burn wounds. The Artaderm ointment had an effective role in controlling burn wound infections due to its antimicrobial and anti-inflammatory properties. In this study, 64 male Wistar rats were randomly divided into 8 groups (n = 8). Four groups received Artaderm, 1% Silver Sulfadiazine (SSD 1%), Cod Liver Oil and Fundermol (Alpha) ointments which used in common practices for burn injuries. Another three groups received Henna, Linseed, and Honey Wax alone and a control group that just underwent a second-degree burn injury without any treatments. A second-degree burn was formed on the back of each rat and dressed daily with one of the agents. Burn wounds were macroscopically and microscopically evaluated on the 7th, 14th, and 21st day after burn induction. Rats treated with the Artaderm ointment had significantly faster wound contraction as well as shorter healing time than the rest groups. No scar was observed in rats treated with the Artaderm ointment on the 21st day, while this level of improvement was not observed in other groups at the same time. More than 90% of wounds were healed after on the 14th day in rats treated with Artaderm (94.10 ± 0.18) and Alpha (92.05 ± 0.23) ointments. According to these findings, it can be concluded that Artaderm herbal ointment can be used as a proper alternative for healing of wounds in second-degree burns.

To compare the effects of ciclosporine A (2%) eye drop and tacrolimus (0.03%) eye ointment on children with vernal keratoconjunctivitis (VKC) who were not responding to corticosteroid eye drops. A prospective comparative study was carried out on children who were diagnosed with refractory VKC at the ophthalmology clinic in Benha University, Delta area, Egypt, during the period from October 2019 to February 2020. Fifty-nine patients completed this study. Regarding the individual symptom score, redness, burning, photophobia, and foreign body sensation were significantly reduced in the tacrolimus group compared to those in the ciclosporine A group during the 1st week (p

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus, xerosis, and eczematous lesions. In Japan, treatment options, such as topical corticosteroids and tacrolimus, are associated with efficacy and safety concerns. Crisaborole ointment, 2%, is a topical non-steroidal anti-inflammatory agent approved in several countries for the treatment of mild-to-moderate AD. This phase 2b, randomized, double-blind study (NCT03954158) assessed the efficacy and safety of two crisaborole regimens versus vehicle in the treatment of Japanese patients aged ≥2 years with mild-to-moderate AD. Each patient was assigned to one of two age cohorts (≥12 or 2-11 years) and randomized to crisaborole once daily (QD) or twice daily (BID). All patients had two target lesions that were each randomly assigned to crisaborole or vehicle at baseline and treated for 2 weeks. The primary endpoint was change from baseline in total sign score (TSS) in crisaborole- or vehicle-treated target lesions on day 15, and secondary endpoints included change from baseline in Investigator's Static Global Assessment (ISGA) and pruritic assessments (Cohort 1: peak pruritus numeric rating scale [NRS]; Cohort 2: Itch Severity Scale Self-Report and Caregiver-Reported Itch Severity NRS) and incidence of treatment-emergent adverse events (TEAEs). This study comprised 81 patients (Cohort 1: n = 41; Cohort 2: n = 40). Crisaborole-treated lesions showed statistically significant reductions in TSS versus vehicle-treated lesions at day 15 (p < 0.01), and numerically larger decreases in TSS were observed with crisaborole BID versus crisaborole QD in both cohorts. Furthermore, crisaborole-treated lesions generally demonstrated greater decreases in ISGA, peak pruritus NRS, Itch Severity Scale, and Caregiver-Reported Itch Severity NRS versus vehicle-treated lesions irrespective of regimen or cohort. Overall, TEAEs were mild; the most frequently reported TEAEs was application site irritation. In summary, both crisaborole regimens, particularly crisaborole BID, demonstrated efficacy and were well tolerated.

Tungiasis (sand flea disease) is an epidermal parasitic skin disease occurring in resource-limited communities. There is no standard treatment for tungiasis, and available treatment options are scarce. To our knowledge, this is the first systematic review aimed to assess randomised controlled trials (RCTs) investigating interventions for tungiasis. We systematically searched databases including MEDLINE (EBSCOhost), CENTRAL, CINAHL, PubMed, Web of Science, SciELO, LILACS and Embase (Scopus) for RCTs in any language, from inception of the databases until June 12, 2021. RCTs exploring preventive and therapeutic interventions for tungiasis were eligible. We used the revised Cochrane Collaboration's risk of bias tool to assess the risk of bias and Jadad scale to quantify the methodological quality of the RCTs. Of the 1839 identified records, only eight RCTs involving 808 participants were included, and several methodological deficiencies were identified in most of the trials. Trial interventions included: oral drugs niridazole and ivermectin and topical interventions of ivermectin lotion, metrifonate lotion, thiabendazole lotion, thiabendazole ointment, dimeticones (NYDA), and a neem seed and coconut oils-based mixture for treatment and coconut oil-based lotion (Zanzarin) for prevention. The coconut oil-based lotion for prevention and dimeticones for treatment of tungiasis have displayed the most promise. Most of the RCTs included in this study had low methodological quality. There is a clear unmet need for high-quality RCTs examining safe and effective prevention and treatment alternatives of tungiasis in endemic settings.

Purpose: We aim to compare the incidence of corneal epithelial defects after laser for retinopathy of prematurity (ROP) with and without the use of postoperative erythromycin ointment. Methods: In this retrospective observational cohort study, a total of 100 infants (200 eyes) consecutively treated with laser for ROP between 2012 and 2018. The primary outcome was presence or absence of corneal epithelial defect using fluorescein on bedside examination within the first week following laser for ROP. Additional data assessed included: the use of postoperative prophylactic erythromycin ointment for 1 week, postoperative day on which examination using fluorescein occurred, presence of corneal opacity, gender, birth weight, and gestation age. The presence or absence of postoperative corneal epithelial defects was compared between eyes receiving postoperative erythromycin ointment or not using a Fisher's exact test. Results: Postoperative corneal epithelial defects were more common in eyes which did not receive postoperative erythromycin (7 of 40 eyes; 17.5%), compared to eyes which did receive erythromycin (1 of 160 eyes; 0.6%; P < 0.0001). Postoperative bedside examinations with fluorescein were performed within 2 days of surgery on 136 of 200 of eyes (68%). Corneal opacities were noted in 3 of 200 eyes (1.5%). Conclusion: We observed less corneal epithelial defects in eyes which received postoperative erythromycin ointment for 1 week after laser for ROP than in those which did not. While multiple variables may influence the presence or absence of postoperative corneal epithelial defects following laser for ROP, consideration for postoperative lubricating ointment following laser for ROP seems reasonable.

BACKGROUND There is increasing evidence regarding the wound healing potential of platelet-derived autologous by-products. We provide preliminary data regarding the use of a new plasma rich in growth factors-derived autologous topical ointment for the management of hard-to-heal wounds. CASES Four patients suffering from difficult-to-heal wounds were treated with the autologous ointment. Within 2 to 8 weeks, all wounds healed completely with no signs of infection or functional impairment of the affected limbs. No adverse events were reported. CONCLUSION Randomized and controlled trials are needed to determine the clinical efficacy of the autologous ointment. Nevertheless, results from this multiple case series indicate that this approach may be useful for accelerating the re-epithelization of difficult-to-heal wounds.

For elemental impurities that have been studied for transcutaneous absorption, the available data are rarely suitable for proper toxicological risk assessment — there are multiple factors that can influence this dermal absorption. Hence, in our studies, we applied generic and conservative approach — cutaneous permitted daily exposure (CPDE) described in International Conference on Harmonisation’s Q3D Guideline on Elemental Impurities (ICH Q3D). The aim of this article is toxicological risk assessment (TRA) of dermal exposure of patients exposed to nickel and chromium due to application of ointments with Marjoram herb extract (Majoranae herbae extractum) available in Polish pharmacies (n = 5, because only five manufacturers produce this kind of pharmaceutical products in Poland). To make the appropriate TRA approach, we considered (1) raw results (metal per kg of ointment), (2) one-time administration of applied ointments, and (3) daily exposure versus CPDE. Due to the fact the concentrations of Ni generally present in cutaneous products as impurities are not considered sufficient to induce sensitization, the cutaneous and transcutaneous concentration limits (CTCLs) approach was applied for this element assessment. The toxicological analysis was carried out using microwave-assisted wet digestion with concentrated nitric acid and electrothermal atomization atomic absorption spectrometry. Our results show that the ointments with Marjoram herb extract from pharmacies in Poland represent a potential health hazard to patients; however, there may be a requirement for the monitoring of impurities of nickel in future. To the best of our knowledge, this paper is the first study about nickel and chromium content in ointments with Marjoram herb extract (Majoranae herbae extractum).

Burn wound progression is an inflammation-driven process where an initial partial-thickness thermal burn wound can evolve over time to a full-thickness injury. We have developed an oil-in-water nanoemulsion formulation (NB-201) containing benzalkonium chloride for use in burn wounds that is antimicrobial and potentially inhibits burn wound progression. We used a porcine burn injury model to evaluate the effect of topical nanoemulsion treatment on burn wound conversion and healing. Anesthetized swine received thermal burn wounds using a 25-cm2 surface area copper bar heated to 80°C. Three different concentrations of NB-201 (10, 20, or 40% nanoemulsion), silver sulfadiazine cream, or saline were applied to burned skin immediately after injury and on days 1, 2, 4, 7, 10, 14, and 18 postinjury. Digital images and skin biopsies were taken at each dressing change. Skin biopsy samples were stained for histological evaluation and graded. Skin tissue samples were also assayed for mediators of inflammation. Dermal treatment with NB-201 diminished thermal burn wound conversion to a full-thickness injury as determined by both histological and visual evaluation. Comparison of epithelial restoration on day 21 showed that 77.8% of the nanoemulsion-treated wounds had an epidermal injury score of 0 compared to 16.7% of the silver sulfadiazine-treated burns (P = .01). Silver sulfadiazine cream- and saline-treated wounds (controls) converted to full-thickness burns by day 4. Histological evaluation revealed reduced inflammation and evidence of skin injury in NB-201-treated sites compared to control wounds. The nanoemulsion-treated wounds often healed with complete regrowth of epithelium and no loss of hair follicles (NB-201: 4.8 ± 2.1, saline: 0 ± 0, silver sulfadiazine: 0 ± 0 hair follicles per 4-mm biopsy section, P < .05). Production of inflammatory mediators and sequestration of neutrophils were also inhibited by NB-201. Topically applied NB-201 prevented the progression of a partial-thickness burn wound to full-thickness injury and was associated with a concurrent decrease in dermal inflammation.

Background Clinical benefits of local antibiotics as an adjunct to nonsurgical treatment of peri-implantitis have been widely reported, but most studies evaluated incipient peri-implantitis lesions, and showed incomplete treatment success rates. Purpose To assess the clinical and microbiological outcomes of administering metronidazole in combination with minocycline as a local adjunct to the nonsurgical treatment of peri-implantitis. Materials and methods One hundred and eighteen subjects with peri-implantitis were recruited in a four-center, three-arm, and 12-week randomized controlled trial. Subjects were randomly assigned to receive one of the following treatments: (a) MM-mechanical debridement + metronidazole-minocycline ointment, (b) MC-mechanical debridement + minocycline ointment, (c) NST-mechanical debridement only. Results Except for four subjects who was excluded during the trial, a total of 114 patients with 114 implants (one implant per each patient) finally completed the trial and were included in the analyses. Multivariate logistic regression analysis revealed that the treatment success rates (absence of bleeding or suppuration on probing, and sites showing pocket probing depth [PPD] ≥5 mm) on at 12 weeks were higher in MM-group patients (31.6%) and MC-group patients (20.5%) compared to NST-group patients (2.7%; p = 0.011 and 0.040, respectively). Subjects with deepest PPD ≥8 mm showed a significant difference in the PPD reduction between MM and MC groups at week 4 (p = 0.025) and week 12 (p = 0.047). Detection ratio of Tannerella forsythia was significantly lower for MM group than MC group (p = 0.038). Conclusions Additive use of either MM or MC results in significantly higher treatment success rates compared to sole mechanical debridement in nonsurgical treatment of peri-implantitis. Moreover, MM contributes to a significantly greater reduction in the PPD compared to MC in deep pockets (cris.nih.go.kr KCT0004557).

Burn injuries represent a global public health concern. The guidelines for burn care mention that the treatment of burn injuries depends on the type of burn injury, depth of tissue, area of wounds, and site on the body. At present, several topical antimicrobial agents are used in the treatment of burn wounds as a first choice. This study aims to investigate the effectiveness of the compound polymyxin B topical agents for the treatment of burn wounds. PubMed, Web of Science, ProQuest, and China National Knowledge Infrastructure databases were searched for articles published until January 2021. The studies that conducted clinical trials comparing compound polymyxin B ointment with other treatment reagents for burn wound treatment were included. A total of three outcomes, which were investigator-assessed clinical response, including mortality, bacterial counts, efficacy and safety were included for analysis in this study. In total, 12 randomized controlled trials, 1 clinical trial, 2 prospective studies, and 1 retrospective study were extracted. The result of mortality showed no significant difference (risk ratio [RR]: 0.70, 95% CI: 0.21–2.31, P = .56); wound healing revealed an RR of 1.59 (95% CI: 1.40–1.81, P < .001); time to heal revealed a mean difference of −5.09 (95% CI: −6.31 to −3.86) days (P < .001); scar incidence was not significantly lower in the treatment group (RR: 0.70, 95% CI: 0.38–1.30, P = .26); and adverse event incidence was significantly lower in the treatment group (RR: 0.26, 95% CI: 0.09–0.72, P < .01). The compound polymyxin B ointment shows the effectiveness of increase in the wound healing and accelerates the time of healing with fewer adverse effects.

Objectives Skin and soft tissue infections commonly affect athletes and can lead to cluster outbreaks if not managed appropriately. We report the findings of an investigation into an outbreak of community-acquired Staphylococcus aureus infection in an Australian professional football team. Design Retrospective cross-sectional study. Methods Nose, axilla, groin and throat swab were collected from 47 participants. MRSA and MSSA isolates underwent antibiotic susceptibility testing, binary typing and whole genome sequencing. Infection control practitioners (ICPs) investigated the training grounds for risk factors in the transmission of S. aureus. Results Almost half of the participants (n = 23, 48.9%) were found to be colonised with MSSA. An outbreak cluster of MRSA ST5 closely related to the fusidic acid-resistant New Zealand NZAK3 clone was identified in a group of four players. MSSA ST15 and MSSA ST291 strains were found to have colonised and spread between two and five players, respectively. All participants were advised to undergo decolonisation treatment consisting of 4% chlorhexidine body wash and mupirocin nasal ointment for ten days. The ICP team identified several unhygienic practices within the club’s shared facilities that may have played a role in the transmission of S. aureus. Conclusions We report for the first time a community-associated S. aureus outbreak involving the highly successful fusidic acid-resistant MRSA ST5 clone in a professional football club associated with inadequate hygiene procedures. Management and prevention of S. aureus relies heavily on hygiene education and adherence to personal and environmental hygiene practices and policies.

Purpose: To compare the efficacy of 2% rebamipide suspension with topical cyclosporine and tacrolimus for managing vernal keratoconjunctivitis (VKC)Methods: In this prospective, interventional study, 38 patients with moderate to severe VKC were allocated to receive either 2% rebamipide in one eye and 0.03% tacrolimus ointment in the contralateral eye (n = 19) or 2% rebamipide in one eye and 0.05% cyclosporine in the contralateral eye (n = 19) for 12 weeks. Ten ocular signs and 7 symptoms were graded on a scale of 0-3 each for each eye at every visit.Results: Total sign and symptom scores reduced significantly in all 4 subgroups (all p's

The tubulin polymerization and Src kinase signaling inhibitor tirbanibulin is being investigated as a topical treatment for actinic keratosis, a precursor of squamous-cell carcinoma.In two identically designed double-blind trials, we randomly assigned, in a 1:1 ratio, adults with actinic keratoses on the face or scalp to receive either topical tirbanibulin or vehicle (placebo) ointment. The ointment was applied by the patients to a 25-cmA total of 702 patients were enrolled in the two trials (351 patients per trial). Complete clearance in trial 1 occurred in 44% of the patients (77 of 175) in the tirbanibulin group and in 5% of those (8 of 176) in the vehicle group (difference, 40 percentage points; 95% confidence interval [CI], 32 to 47; P0.001); in trial 2, the percentages were 54% (97 of 178 patients) and 13% (22 of 173), respectively (difference, 42 percentage points; 95% CI, 33 to 51; P0.001). The percentages of patients with partial clearance were significantly higher in the tirbanibulin groups than in the vehicle groups. At 1 year, the estimated percentage of patients with recurrent lesions was 47% among patients who had had a complete response to tirbanibulin. The most common local reactions to tirbanibulin were erythema in 91% of the patients and flaking or scaling in 82%. Adverse events with tirbanibulin were application-site pain in 10% of the patients and pruritus in 9%, all of which resolved.In two identically designed trials, tirbanibulin 1% ointment applied once daily for 5 days was superior to vehicle for the treatment of actinic keratosis at 2 months but was associated with transient local reactions and recurrence of lesions at 1 year. Trials comparing tirbanibulin with conventional treatments and that have longer follow-up are needed to determine the effects of tirbanibulin therapy on actinic keratosis. (Funded by Athenex; ClinicalTrials.gov numbers, NCT03285477 and NCT03285490.).

Background: Studies comparing head-to-head treatment modalities for anogenital warts are lacking. Aim: We sought to compare a short, 8-week course of imiquimod 5% cream to versus the standard 4 week course of podophyllotoxin in the treatment of anogenital warts and to assess factors that may affect response to treatment. Methods: This was a retrospective cohort study. We reviewed medical files of otherwise healthy patients with a first episode of anogenital warts who were treated with either a short, 8-week course of imiquimod or the standard 4-week course of podophyllotoxin. Inverse probability of treatment weighted (IPTW). Logistic regression was employed to evaluate factors that may affect response to therapy. Results: The study included 347 patients. In patients with lesions on dry, keratinized anatomical sites, the complete clearance rates were 7.6% for imiquimod and 27.9% for podophyllotoxin (P < 0.001). In patients with lesions on moist, partially keratinized sites, no difference between the treatments was revealed. Significant predictors of > 50% reduction in wart area were location of lesions [odds ratio (OR) (95% confidence interval (CI)): 3.6 (1.84–7.08), P = 0.0002] for “partially keratinized” versus “keratinized” sites and treatment used [OR (95% CI): 1.79 (1.08–2.97), P = 0.024] for podophyllotoxin versus imiquimod. Limitations: The retrospective design of the study was a limitation that we mitigated against with the use of IPTW logistic regression. Conclusion: A standard 4 week course of Podophyllotoxin was more effective than an 8-week course of imiquimod only for lesions on keratinized sites. Treatment with podophyllotoxin and location of lesions on partially keratinized sites were independent predictors of >50% reduction in wart area.

Experimental dermatology 30(5), 745-750 (2021). doi:10.1111/exd.14266, Published by Blackwell, Oxford

Background: Diaper dermatitis (DD) is a prevalent skin disease in children, which causes child discomfort and parental concern. This study aimed to compare the effects of aloe vera ointment with routine treatment on the severity of DD in hospitalized children. Materials and Methods: This double-blinded randomized clinical trial was carried out on 60 children aged less than two years admitted to Tabriz pediatric hospital in Iran from February to June 2017. Using convenience sampling method, the patients were assigned into two equal groups (n=30 in each) of intervention and control. The intervention group received routine combination treatment, whereas the control group received aloe vera ointment. The patients were examined on the first, third, and sixth days of the study. Data analysis was performed using SPSS software (version 22) and descriptive and analytical statistics. Results: The severity of DD in both groups improved on the sixth day compared to the first day. In comparison, no significant difference was observed between the two groups regarding the severity of dermatitis (P>0.05). Conclusion: Herbal products cause fewer side effects than chemical products and seem to have significant pharmacological effects on the skin. Thus, aloe vera ointment appears to help treat DD and, with further studies, may emerge as a possible therapeutic option.

BACKGROUND Tacrolimus has been used to treat various inflammatory skin diseases, but its safety for topical application on the oral mucosa is unknown. Exfoliative cheilitis (EC) is a chronic inflammatory disorder of the lips characterised by repeated scaling; it is difficult to manage. The aim of this study was to assess the efficacy and safety of tacrolimus 0.03% ointment as a topical treatment in patients with EC. METHODS In this randomised controlled clinical trial, 40 patients with EC were randomly assigned to receive either tacrolimus 0.03% ointment (experimental group, n = 20) or triamcinolone acetonide 0.1% cream (control group, n = 20) treatment for a 3-week period. Medication was administered in 3, 2 and 1 daily doses during the first, second and third weeks, respectively. The patients with complete healing were followed up for 3 months. The clinical outcomes were measured, including the scores regarding signs (scale, dryness, rhagades and swelling) and symptoms (rough, dry, pain, pruritus and burning sensation) at every visit. Blood concentrations of tacrolimus were assessed. RESULTS After the 3-week treatment, healing rates of scale in the experimental and control groups were 65% and 10%, respectively (P = .018). Improvement in all signs and two symptoms (rough, pruritus) was much greater in the experimental group (P

Topical sirolimus has become a crucial treatment option for many dermatologic disorders. Because an FDA-approved topical formulation is not commercially available, sirolimus creams, ointments, and gels are professionally prepared by compounding pharmacies. Also, the topical use of a commercially available sirolimus solution approved for oral administration is described regularly. To better guide providers in their decision-making when topical sirolimus is being considered, this article highlights the substantial pharmaceutical and clinical differences between commercial oral solution and compounded preparations specifically designed for topical therapy.

Diffuse plane xanthomas (DPX) is a rare, chronic, metabolic skin disease which can seriously affect the appearance of the patients and result in psychological problems. Existing treatments are seriously limited. Our objective was to assess the efficacy of and tolerance to simvastatin ointment for the treatment of skin lesions in seven DPX patients. In this study, patients were treated twice daily on the right side of the lesions for 10 months with the 1% or 5% simvastatin ointment. Meanwhile, the left body was untreated as a contralateral controlled side. Efficacy was assessed via the change of rash and was further confirmed by histological study. For all seven participants, both the 1% and 5% simvastatin ointments were effective. The histological change in DPX showed significant decrease of foam cells in skin lesions. The immunohistochemical staining of CD68, macrophage scavenger receptor type 1, oxidized low-density lipoprotein receptor 1 and Oil Red O became obviously reduced after treatment. The test medicines were safe with only some skin-related side-effects. This is the first research reported on simvastatin ointment treatment in DPX. Our results are the first to suggest that simvastatin ointment is effective in improving skin lesions of DPX clinically and histopathologically.

Objective To compare the safety and efficacy of 10% sinecatechins (Veregen® ) ointment against placebo in the treatment of usual type vulvar intraepithelial neoplasia (uVIN). Design A Phase II double-blind randomised control trial. Setting A tertiary gynaecological oncology referral centre. Population All women diagnosed with primary and recurrent uVIN. Methods Eligible patients were randomised 1:1 to receive either sinecatechins or placebo ointment (applied three times daily for 16 weeks) and were followed up at 2, 4, 8, 16, 32 and 52 weeks. Main outcome measures The primary outcome measure, recorded at 16 and 32 weeks, was histological response (HR). Secondary outcome measures included clinical (CR) response, toxicity, quality of life and pain scores. Results There was no observed difference in HR between the two arms. However, of the 26 patients who were randomised, all 13 patients who received sinecatechins showed either complete (n = 5) or partial (n = 8) CR, when best CR was evaluated. In placebo group, three patients had complete CR, two had partial CR, six had stable disease and two were lost to follow up. Patients in the sinecatechins group showed a statistically significant improvement in best observed CR as compared with the placebo group (P = 0.002). There was no difference in toxicity reported in either group. Conclusion Although we did not observe a difference in HR between the two treatment arms, we found that 10% sinecatechins application is safe and shows promise in inducing clinical resolution of uVIN lesions and symptom improvement, thus warranting further investigation in a larger multicentre study. Tweetable abstract A randomised control study indicating that sinecatechins ointment may be a novel treatment for uVIN.

Background Burn injury progression in the secondary zone of ischemia is common leading to delayed healing and increased scarring. We hypothesized that a topical surfactant, would reduce burn injury progression in a validated rat comb burn model compared with topical antibiotic ointment. Methods We created 40 comb burns on 20 rats which were randomized to daily topical application of the surfactant or a triple antibiotic ointment. The comb burns consisted of 4 full thickness burns with 3 unburned interspaces between the 4 burns. These unburned interspaces represented the zone of ischemia, and when left untreated, generally progress to full thickness necrosis within several days. Comb burns were assessed daily for the presence of gross necrosis of the interspaces. At 7 days the comb burns were excised and blindly evaluated for the presence of histological evidence of necrosis. The study had 80% power to detect a 25% difference in the percentages of necrotic interspaces on day 7. Results There were no differences in the percentages of histologically necrotic interspaces at 7 days in burns treated with the surfactant or antibiotic ointment (85% [95%CI, 74 to 92] vs. 75% [95%CI, 63 to 84]; mean difference 10% [95%CI −4 to 24]). There were also no between group differences in the percentages of grossly necrotic interspaces on any of the seven days of the experiment. The surfactant remained intact and adherent while the antibiotic had been absorbed at each daily dressing change. Conclusions A topical surfactant did not reduce injury progression in the rat comb burn model when compared with antibiotic ointment. The surfactant was more durable than the antibiotic ointment.

Bloodroot (Sanguinaria canadensis) is a plant, native to North America, containing bioactive compounds that interrupt biological processes. It has been around for centuries and is known for its medicinal properties. Today, naturopathic remedies are becoming more and more popular, especially for skin ailments. There are an alarming number of online vendors marketing their bloodroot-containing products as cures for skin cancer without any scientific evidence supporting such claims. Clinical data concerning the efficacy of bloodroot primarily come from case studies with unfavorable outcomes involving patients who self-treated with bloodroot-containing black salves. However, recent preclinical studies have concluded that sanguinarine, the active component of bloodroot, shows positive evidence of being an efficacious treatment for skin cancers at micromolar doses. This article reviews the mechanism of action of bloodroot as a skin cancer treatment, its misuse in clinical dermatology, and the FDA's stance on products containing bloodroot that are marketed and sold to laypersons. Members of the public should be made aware of the dangers of self-treating with bloodroot-containing products through effective communication and education by clinicians.

Abstract. Vitamin B12, a water-soluble vitamin, plays a vital role in the formation of hematopoietic stem cells and has been associated with oral mucosal diseases, mainly recurrent aphthous stomatitis (RAS). The latter is a debilitating condition, and B12 was proposed as a potential treatment given its role in regenerating oral mucosal tissue. There is conflicting evidence that B12 deficiency causes RAS. Five of the seven randomized controlled trials reviewed used the inactive form of B12 (cyanocobalamin) as intervention, while the other two used the active form (methylcobalamin). Of the latter two, buccal discs (500 μg B12) showed significant improvement and reduced perceived pain in 77% of the subjects, and submucosal injections showed a significant difference in pain, starting from the second day. Moreover, three studies administered vitamin B12 sublingually with different dosages, which revealed that the higher dose (1000 μg) achieved a significant reduction in outbreaks, number, and duration of ulcers, especially after six months. Multivitamins showed no difference in new RAS episodes and duration. Injectable B12 was compared with the oral form, and nearly 50% of the injection group reported a desired response by the eighth week. An ointment form (500 μg) showed a significant reduction in pain levels after two days of treatment. Based on the available literature, we suggest that a daily dose of 1000 μg of vitamin B12 sublingually for six months can be used to treat RAS. Nevertheless, this conclusion should be considered tentative due to the lack of high quality, large scale studies.

Purpose: Ocular complications are common in the critical care setting but are frequently missed due to the focus on life-saving organ support. The SARS-CoV-2 (COVID-19) pandemic has led to a surge in critical care capacity and prone positioning practices which may increase the risk of ocular complications. This article aims to review all ocular complications associated with prone positioning, with a focus on challenges posed by COVID-19. Materials and Methods: A literature review using keywords of “intensive care”, “critical care”, “eye care”, “ocular disorders”, “ophthalmic complications,” “coronavirus”, “COVID-19,” “prone” and “proning” was performed using the electronic databases of PUBMED, EMBASE and CINAHL. Results: The effects of prone positioning on improving respiratory outcomes in critically unwell patients are well established; however, there is a lack of literature regarding the effects of prone positioning on ocular complications in the critical care setting. Sight-threatening ophthalmic disorders potentiated by proning include ocular surface disease, acute angle closure, ischemic optic neuropathy, orbital compartment syndrome and vascular occlusions. Conclusions: COVID-19 patients may be more susceptible to ocular complications with increased proning practices and increasing demand on critical care staff. This review outlines these ocular complications with a focus on preventative and treatment measures to avoid devastating visual outcomes for the patient.

Introduction: Natural agents with antioxidant and anti-inflammatory properties are safer than synthetic agents and may improve wound healing. Objective: The purpose of this study is to evaluate the in vivo wound healing potential of an ointment prepared from Trifolium repens hydroethanolic extract (T repens) concerning excisional wounds in a rat model. Materials and methods: Seventy-two adult Wistar rats were divided into 4 groups: a control group and 3 groups of animals treated with 1.5% T repens, 3% T repens, and 6% T repens. A full-thickness wound with an area of 314 mm2 was created in each rat. To investigate the effect of T repens on wound healing, the wound area, histological analyses (eg, angiogenesis, fibroblast, fibrocyte, mast-cell distribution), intracytoplasmic carbohydrate storage, and B-cell lymphoma 2-like protein 4 (BAX), B-cell lymphoma 2 (Bcl-2), and p53 gene expression in the wound tissue were evaluated for 21 days. Antioxidant activity was further measured by 2,20-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and 2,2-Di(4-tert-octylphenyl)-1-picrylhydrazyl (DPPH) assays. Results: The animals in the treated groups showed higher wound contraction ratios (P ⟨ .05), angiogenesis, fibroblast, fibrocyte, and mast-cell distribution and intracytoplasmic carbohydrate storage compared with the control group (P ⟨ .05). Moreover, the topical administration of T repens increased the messenger ribonucleic acid (mRNA) level of Bcl-2 and reduced the BAX and p53 mRNA levels (P ⟨ .05). These findings further revealed the strong antioxidant activity of T repens. Conclusions: The topical administration of T repens accelerated wound healing by increasing angiogenesis; fibroblast, fibrocyte, and mast-cell distribution; intracytoplasmic carbohydrate storage; and modulation in genes involved in apoptosis in a rat model.