Tranexamic acid in melasma: A focused review on drug administration routes.

BACKGROUND: Melasma is a disorder of hyperpigmentation and vascularization often found in women between the ages of 20 and 40. The pathogenesis is unknown, but melasma often occurs in sun-exposed areas of the face, forearms, and back. Risk factors include family history, increased estrogen/progesterone, certain medications, and UV exposure. Melasma is typically treated with topical hydroquinone (HQ); however, it is often refractory to treatment. Tranexamic acid (TXA) is a plasmin inhibitor used off-label in the treatment of melasma. TXA can be administered orally, topically, or intralesionally. AIMS: The purpose of this review is to characterize the wide variety of TXA delivery methods for melasma treatment and the efficacy of these methods compared with traditional treatments. PATIENTS/METHODS: A comprehensive PubMed and Embase search was conducted in May 2022 using the phrases tranexamic acid and melasma. Forty-six articles were included in this review. RESULTS: Oral, intralesional, and topical TXA is safe and effective treatments for melasma. They have been studied in a variety of randomized controlled trials and have been compared with several traditional treatments. Overall, MASI scores in patients using TXA in any form improved. CONCLUSIONS: Oral TXA was found to be the most effective, especially in cases of refractory melasma; however, it caused GI upset and menstrual irregularities in many patients. The pro-thrombotic nature of this drug must be considered before safely prescribing to patients. Intralesional injections and microneedling with topical TXA were found to be effective alternatives to oral treatment. Lastly, topical TXA alone was found to be the least effective method but can be combined with other cosmeceuticals to improve outcomes. Topical TXA was also found to be better tolerated than hydroquinone, a traditional topical melasma treatment.

Imiquimod-Associated Localized Skin Ulceration in a Patient With Uncontrolled Diabetes.

BACKGROUND: Human papillomavirus, one of the most common viral infections worldwide, frequently manifests as condyloma acuminata, or anogenital warts. First-line treatment of this condition includes the use of imiquimod, a topical immunomodulator. CASE: We describe a case of a localized skin ulceration necessitating surgical debridement after the use of topical imiquimod for 24 hours in a patient with uncontrolled type 2 diabetes mellitus. After debridement, the patient's wound healed appropriately, with regular wound clinic visits and diabetes education. CONCLUSION: Health care professionals should use caution when prescribing imiquimod in patients with uncontrolled type 2 diabetes mellitus.

Total Dystrophic Onychomycosis Successfully Treated with Efinaconazole Topical Solution in Times of Coronavirus Disease of 2019: A Case Study.

Toenail onychomycosis is a common condition that is equally challenging for podiatrists and patients. This case study documents a 26-year-old woman with bilateral total dystrophic onychomycosis of at least 5 years' duration. She had previously failed to respond to treatment with ciclopirox nail lacquer 8% and, despite hiding her condition with nail polish, was suffering from embarrassment, distress, and low self-esteem. At initial consultation, 100% of both great toenails was affected. After discussion of all treatment options, the patient opted for topical efinaconazole 10% solution, once daily for 48 weeks. Significant improvement was noted at the first (4-week) assessment period. This improvement was maintained through each subsequent virtual consultation, and complete cure was seen at a 30-week follow-up visit. To the author's knowledge, this is the first published report on the use of efinaconazole in total dystrophic onychomycosis. It suggests that the product may be effective in patients with even the most severe and treatment-recalcitrant disease, who are unwilling or unable to tolerate systemic antifungal therapy.

Topical TMPRSS2 inhibition prevents SARS-CoV-2 infection in differentiated human airway cultures.

BACKGROUND: There are limited effective prophylactic/early treatments for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Viral entry requires spike protein binding to the angiotensin-converting enzyme-2 receptor and cleavage by transmembrane serine protease 2 (TMPRSS2), a cell surface serine protease. Targeting of TMPRSS2 by either androgen blockade or direct inhibition is in clinical trials in early SARS-CoV-2 infection. METHODS: We used differentiated primary human airway epithelial cells at the air-liquid interface to test the impact of targeting TMPRSS2 on the prevention of SARS-CoV-2 infection. RESULTS: We first modelled the systemic delivery of compounds. Enzalutamide, an oral androgen receptor antagonist, had no impact on SARS-CoV-2 infection. By contrast, camostat mesylate, an orally available serine protease inhibitor, blocked SARS-CoV-2 entry. However, oral camostat is rapidly metabolised in the circulation, with poor airway bioavailability. We therefore modelled local airway administration by applying camostat to the apical surface of differentiated airway cultures. We demonstrated that a brief exposure to topical camostat effectively restricts SARS-CoV-2 infection. CONCLUSION: These experiments demonstrate a potential therapeutic role for topical camostat for pre- or post-exposure prophylaxis of SARS-CoV-2, which can now be evaluated in a clinical trial.

Interferon and Toll-Like Receptor 7 Response in COVID-19: Implications of Topical Imiquimod for Prophylaxis and Treatment.

BACKGROUND: The innate immune system is recognized as an essential aspect of COVID-19 pathogenesis. Toll-like receptors (TLRs) are important in inducing antiviral response, triggering downstream production of interferons (IFNs). Certain loss-of-function variants in TLR7 are associated with increased COVID-19 disease severity, and imiquimod (ImiQ) is known to have immunomodulating effects as an agonist of TLR7. Given that topical imiquimod (topImiQ) is indicated for various dermatologic conditions, it is necessary for dermatologists to understand the interplay between innate immunity mechanisms and the potential role of ImiQ in COVID-19, with a particular focus on TLR7. SUMMARY: Our objective was to survey recent peer-reviewed scientific literature in the PubMed database, examine relevant evidence, and elucidate the relationships between IFNs, TLR7, the innate immune system, and topImiQ in the context of COVID-19. Despite limited studies on this topic, current evidence supports the critical role of TLRs in mounting a strong immune response against COVID-19. Of particular interest to dermatologists, topImiQ can result in systemic upregulation of the immune system via activation of TLR7. Key Message: Given the role of TLR7 in the systemic activation of the immune system, ImiQ, as a ligand of the TLR7 receptor, may have potential therapeutic benefit as a topical immunomodulatory treatment for COVID-19.

Upadacitinib plus topical corticosteroids in atopic dermatitis: Week 52 AD Up study results.

BACKGROUND: Primary (week 16) results from the ongoing phase 3, double-blind AD Up study (NCT03568318) demonstrate a positive benefit-risk profile for upadacitinib + topical corticosteroid (TCS) in patients with moderate-to-severe atopic dermatitis. OBJECTIVE: We evaluated the efficacy and safety of upadacitinib + TCS through 52 weeks. METHODS: Patients aged 12 to 75 years with chronic moderate-to-severe atopic dermatitis (≥10% of body surface area affected, Eczema Area and Severity Index [EASI] ≥16, Validated Investigator's Global Assessment for atopic dermatitis [vIGA-AD] ≥3, and Worst Pruritus Numerical Rating Scale [WP-NRS] score ≥4) were randomized 1:1:1 to once-daily upadacitinib 15 mg + TCS, upadacitinib 30 mg + TCS, or placebo (PBO) + TCS (rerandomized at week 16 to upadacitinib + TCS). Safety and efficacy, including proportion of patients experiencing ≥75% improvement in EASI (EASI-75), vIGA-AD of clear/almost clear with improvement ≥2 grades (vIGA-AD 0/1), and WP-NRS improvement ≥4, were assessed through week 52. Missing data were primarily handled by nonresponse imputation incorporating multiple imputation for missing values due to coronavirus disease 2019 (COVID-19). RESULTS: Of 901 patients, 300 were randomized to upadacitinib 15 mg + TCS, 297 to upadacitinib 30 mg + TCS, and 304 to PBO + TCS. For all end points, efficacy for upadacitinib 15 mg + TCS and upadacitinib 30 mg + TCS at week 16 was maintained through week 52. At week 52, the proportions of patients treated with upadacitinib 15 mg + TCS and upadacitinib 30 mg + TCS who experienced EASI-75 were 50.8% and 69.0%, respectively; 33.5% and 45.2%, respectively, experienced vIGA-AD 0/1; and 45.3% and 57.5%, respectively, experienced WP-NRS improvement ≥4. Upadacitinib + TCS was well tolerated through 52 weeks; no new important safety risks beyond the current label were observed. No deaths were reported; major adverse cardiovascular events and venous thromboembolic events were infrequent (≤0.2/100 patient-years). CONCLUSIONS: Results through 52 weeks demonstrate long-term maintenance of efficacy and a favorable safety profile of upadacitinib + TCS in patients with moderate-to-severe AD.

The SARS-CoV-2-Inactivating Activity of Hydroxytyrosol-Rich Aqueous Olive Pulp Extract (HIDROX®) and Its Use as a Virucidal Cream for Topical Application.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally. Although measures to control SARS-CoV-2, namely, vaccination, medication, and chemical disinfectants are being investigated, there is an increase in the demand for auxiliary antiviral approaches using natural compounds. Here we have focused on hydroxytyrosol (HT)-rich aqueous olive pulp extract (HIDROX®) and evaluated its SARS-CoV-2-inactivating activity in vitro. We showed that the HIDROX solution exhibits time- and concentration-dependent SARS-CoV-2-inactivating activities, and that HIDROX has more potent virucidal activity than pure HT. The evaluation of the mechanism of action suggested that both HIDROX and HT induced structural changes in SARS-CoV-2, which changed the molecular weight of the spike proteins. Even though the spike protein is highly glycosylated, this change was induced regardless of the glycosylation status. In addition, HIDROX or HT treatment disrupted the viral genome. Moreover, the HIDROX-containing cream applied on film showed time- and concentration-dependent SARS-CoV-2-inactivating activities. Thus, the HIDROX-containing cream can be applied topically as an antiviral hand cream. Our findings suggest that HIDROX contributes to improving SARS-CoV-2 control measures.

A multi-center trial of exercise and testosterone therapy in women after hip fracture: Design, methods and impact of the COVID-19 pandemic.

BACKGROUND: Up to 75% of hip fracture patients never recover to their pre-fracture functional status. Supervised exercise that includes strength training can improve functional recovery after hip fracture. The role of testosterone replacement for augmenting the effects of exercise in older women after hip fracture is unknown. METHODS: The Starting Testosterone and Exercise after Hip Injury (STEP-HI) Study is a 6-month Phase 3 multicenter randomized placebo-controlled trial designed to compare supervised exercise (EX) plus 1% testosterone topical gel, with EX plus placebo gel, and with enhanced usual care (EUC). Female hip fracture patients age ≥ 65 years are being recruited from clinical centers across the United States. Participants are community dwelling and enrolled within 24 weeks after surgical repair of the fracture. The EX intervention is a center-based program of progressive resistance training. The EUC group receives a home exercise program and health education. Participants receive dietary counseling, calcium and vitamin D. The primary outcome is the Six Minute Walk Distance. Secondary outcomes include physical performance measures, self-reported function and quality of life, and dual energy x-ray absorptiometry measures of body composition and bone mineral density. RESULTS: Enrollment, interventions, and follow-up are ongoing. We describe the impact of the coronavirus disease 2019 pandemic on the trial, including modifications made to allow continuation of the interventions and outcome data collection using remote video and audio technology. CONCLUSIONS: Results from the STEP-HI study are expected to have important clinical and public health implications for management of the growing population of hip fracture patients.

SARS-CoV-2 decontamination of skin with disinfectants active during and after application.

BACKGROUND: The coronavirus disease 2019 pandemic has resulted in high levels of exposure of medical workers to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Hand decontamination is one of the actions recommended to reduce the risk of infection. AIM: Two disinfectants - BIAKOS antimicrobial skin and wound cleanser (AWC) and AWC2 (Sanara MedTech, Fort Worth, TX, USA) - were tested to determine whether they can inactivate SARS-CoV-2 upon contact or as a coating applied before contact with the virus. METHODS: The ability of AWC and AWC2 to inactivate SARS-CoV-2 was tested in liquid and dried form on plastic surfaces and porcine skin. FINDINGS: AWC and AWC2 were effective in reducing the infectious titre of SARS-CoV-2 in liquid form during application and in dried form 4 h after application. Virus on skin was reduced up to 2 log10-fold and 3.5 log10-fold after treatment with AWC and AWC2, respectively. CONCLUSION: Application of AWC and AWC2 to skin reduces the level of SARS-CoV-2 and the risk of infection.

Glycyrrhizin: An old weapon against a novel coronavirus.

Currently, over 100 countries are fighting against a common enemy, the severe acute respiratory syndrome coronavirus (SARS-CoV)-2, which causes COVID-19. This has created a demand for a substance whose effectiveness has already been demonstrated in a similar scenario. Glycyrrhizin (GZ) is a promising agent against SARS-CoV-2 as its antiviral activity against SARS-CoV has already been confirmed. It is worthwhile to extrapolate from its proven therapeutic effects as there is a high similarity in the structure and genome of SARS-CoV and SARS-CoV-2. There are many possible mechanisms through which GZ acts against viruses: increasing nitrous oxide production in macrophages, affecting transcription factors and cellular signalling pathways, directly altering the viral lipid-bilayer membrane, and binding to the ACE2 receptor. In this review, we discuss the possible use of GZ in the COVID-19 setting, where topical administration appears to be promising, with the nasal and oral cavity notably being the potent location in terms of viral load. The most recently published papers on the distribution of ACE2 in the human body and documented binding of GZ to this receptor, as well as its antiviral activity, suggest that GZ can be used as a therapeutic for COVID-19 and as a preventive agent against SARS-CoV-2.

The Use of Topical Oxygen Therapy to Treat a Calciphylaxis Wound During a Global Pandemic: A Case Report.

INTRODUCTION: Calciphylaxis is a rare, highly morbid pathological syndrome of vascular calcification and tissue necrosis. It is predominantly seen in patients with end-stage renal disease (ESRD) on chronic dialysis. There is no definitive standard of care for calciphylaxis, and the overall prognosis for patients, particularly those with ulcerated lesions, is bleak. One important role of wound care clinicians during the COVID-19 pandemic is to ensure that the continuity of care of an at-risk population is maintained while limiting the patient's potential exposure to the virus. Innovative therapies paired with alternative treatment sites of service are one such method. CASE REPORT: A 56-year-old female with ESRD on at-home peritoneal dialysis (PD) presented to the outpatient wound clinic with a punch biopsy-proven calciphylaxis lesion. Within days, state-wide "shelter-at-home" orders due to the COVID-19 pandemic went into effect. To prevent disruption in care and to minimize risk to the patient, the lesion was treated with bi-weekly self-application of a continuous topical oxygen therapy (cTOT) device paired with weekly telemedicine visits. The wound completely resolved after 9 weeks of topical oxygen therapy with no complications or device malfunctions. CONCLUSIONS: This case, to the authors' knowledge, is the first to document healing in a calciphylaxis wound with the use of cTOT. Topical oxygen therapy may be a beneficial adjunctive therapy in the treatment of wounds caused by calciphylaxis. Finding creative ways to navigate this current health care crisis is essential to help mitigate risk for vulnerable patients with advanced comorbidities.