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Our previous study demonstrated that our novel herbal remedy, a mixture of Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum Cassia extracts, exhibits a therapeutic effect in 1-chloro-2,4-dinitrobenzene (DNCB)-induced mice by inhibiting the Th-2 inflammatory response upon oral administration. It also ameliorated imbalances in lipid metabolism related to the skin barrier function in keratinocytes, indicating its potential as a topical agent. This study aims to further investigate the therapeutic effects and metabolic mechanisms of its topical application. The anti-atopic effect was evaluated using dermatitis scores, histopathological analysis, and immune cell factors in DNCB-induced mice. Metabolomic profiling of serum and lesional skin was conducted to elucidate the metabolic mechanisms. The topical application significantly reduced dermatitis scores, mast cell infiltration, and serum levels of immunoglobulin E (IgE), IFN-γ, interleukin (IL)-4, IL-17, and thymic stromal lymphopoietin (TSLP), demonstrating its effectiveness in treating atopic dermatitis (AD). Serum metabolomics revealed alterations in fatty acid metabolism related to the pro-inflammatory response. In lesional skin, metabolic markers associated with oxidative stress, immune regulation, and AD symptoms were restored. This study demonstrated its potential as a topical agent in suppressing Th-2 inflammatory responses and improving metabolic abnormalities related to AD symptoms, providing crucial insights for developing natural AD treatments. [ABSTRACT FROM AUTHOR]

Glaucoma encompasses a group of optic neuropathies characterized by complex and often elusive etiopathology, involvihttng neurodegeneration of the optic nerve in conjunction with abnormal intraocular pressure (IOP). Currently, there is no cure for glaucoma, and treatment strategies primarily aim to halt disease progression by managing IOP. This review delves into the etiopathology, diagnostic methods, and treatment approaches for glaucoma, with a special focus on IOP management. We discuss a range of active pharmaceutical ingredients used in glaucoma therapy, emphasizing their chemical structure, pharmacological action, therapeutic effectiveness, and safety/tolerability profiles. Notably, most of these therapeutic agents are administered as topical formulations, a critical aspect considering patient compliance and drug delivery efficiency. The classes of glaucoma therapeutics covered in this review include prostaglandin analogs, beta blockers, alpha agonists, carbonic anhydrase inhibitors, Rho kinase inhibitors, and miotic (cholinergic) agents. This comprehensive overview highlights the importance of topical administration in glaucoma treatment, offering insights into the current state and future directions of pharmacological management in glaucoma. [ABSTRACT FROM AUTHOR]

Our previous study demonstrated that our novel herbal remedy, a mixture of Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum Cassia extracts, exhibits a therapeutic effect in 1-chloro-2,4-dinitrobenzene (DNCB)-induced mice by inhibiting the Th-2 inflammatory response upon oral administration. It also ameliorated imbalances in lipid metabolism related to the skin barrier function in keratinocytes, indicating its potential as a topical agent. This study aims to further investigate the therapeutic effects and metabolic mechanisms of its topical application. The anti-atopic effect was evaluated using dermatitis scores, histopathological analysis, and immune cell factors in DNCB-induced mice. Metabolomic profiling of serum and lesional skin was conducted to elucidate the metabolic mechanisms. The topical application significantly reduced dermatitis scores, mast cell infiltration, and serum levels of immunoglobulin E (IgE), IFN-γ, interleukin (IL)-4, IL-17, and thymic stromal lymphopoietin (TSLP), demonstrating its effectiveness in treating atopic dermatitis (AD). Serum metabolomics revealed alterations in fatty acid metabolism related to the pro-inflammatory response. In lesional skin, metabolic markers associated with oxidative stress, immune regulation, and AD symptoms were restored. This study demonstrated its potential as a topical agent in suppressing Th-2 inflammatory responses and improving metabolic abnormalities related to AD symptoms, providing crucial insights for developing natural AD treatments.

In volumetric modulated arc therapy (VMAT), the effect of an increase in skin surface dose due to topical agents might be negligible. We investigated the bolus effects of three types of topical agents in VMAT for head and neck cancer (HNC). Topical agents of different thicknesses (0.1, 0.5 and 2 mm) were prepared. When each topical agent was set, the surface doses were measured for the anterior static field and VMAT, with and without a thermoplastic mask. No significant differences were observed among the three topical agents. For topical agent thicknesses of 0.1, 0.5 and 2 mm, the increases in surface dose for the anterior static field without the thermoplastic mask were 7–9, 30–31 and 81–84%, respectively. With the thermoplastic mask, the corresponding increases were 5, 12–15 and 41–43%, respectively. The increases in surface dose for VMAT without the thermoplastic mask were 5–8, 16–19 and 36–39%, respectively, and those with the thermoplastic mask were 4, 7–10 and 15–19%, respectively. The rate of increase in surface dose with the thermoplastic mask was smaller than that without the thermoplastic mask. The increase in surface dose with topical agents of clinical standard thickness (0.02 mm) was estimated to be 2% with the thermoplastic mask. The increase in surface dose with topical agents in dosimetric simulation, compared with control situation, is not significant in clinical conditions for HNC patients. [ABSTRACT FROM AUTHOR]

Glaucoma encompasses a group of optic neuropathies characterized by complex and often elusive etiopathology, involvihttng neurodegeneration of the optic nerve in conjunction with abnormal intraocular pressure (IOP). Currently, there is no cure for glaucoma, and treatment strategies primarily aim to halt disease progression by managing IOP. This review delves into the etiopathology, diagnostic methods, and treatment approaches for glaucoma, with a special focus on IOP management. We discuss a range of active pharmaceutical ingredients used in glaucoma therapy, emphasizing their chemical structure, pharmacological action, therapeutic effectiveness, and safety/tolerability profiles. Notably, most of these therapeutic agents are administered as topical formulations, a critical aspect considering patient compliance and drug delivery efficiency. The classes of glaucoma therapeutics covered in this review include prostaglandin analogs, beta blockers, alpha agonists, carbonic anhydrase inhibitors, Rho kinase inhibitors, and miotic (cholinergic) agents. This comprehensive overview highlights the importance of topical administration in glaucoma treatment, offering insights into the current state and future directions of pharmacological management in glaucoma.

ME1111 is a novel antifungal agent currently under clinical development as a topical onychomycosis treatment. A major challenge in the application of topical onychomycotics is penetration and dissemination of antifungal agent into the infected nail plate and bed. In this study, pharmacokinetic/pharmacodynamic parameters of ME1111 that potentially correlate with clinical efficacy were compared with those of marketed topical onychomycosis antifungal agents: efinaconazole, tavaborole, ciclopirox, and amorolfine. An ME1111 solution and other launched topical formulations were applied to an in vitro dose model for 14 days based on their clinical dose and administration. Drug concentrations in the deep layer of the nail and within the cotton pads beneath the nails were measured using liquid chromatography-tandem mass spectrometry. Concentrations of ME1111 in the nail and cotton pads were much higher than those of efinaconazole, ciclopirox, and amorolfine. Free drug concentrations of ME1111 in deep nail layers and cotton pads were orders of magnitude higher than the MIC90 value against Trichophyton rubrum (n = 30). Unlike other drugs, the in vitro antifungal activity of ME1111 was not affected by 5% human keratin and under a mild acidic condition (pH 5.0). The in vitro antidermatophytic efficacy coefficients (ratio of free drug concentration to MIC90s against T. rubrum) of ME1111, as measured in deep nail layers, were significantly higher than those of efinaconazole, tavaborole, ciclopirox, and amorolfine (P < 0.05). This suggests that ME1111 has excellent permeation of human nails and, consequently, the potential to be an effective topical onychomycosis treatment.

Background: Vitiligo is an autoimmune and acquired disease characterized by the destruction of epidermal melanocytes leading to depigmentation of the skin. Although vitiligo is a common disease, there is not a definite cure and conventional therapies can lead to serious adverse effects. Turmeric has been widely studied for its anti‐inflammatory, antioxidant, and anti‐cell proliferation, while it is a cost‐benefit and available treatment for a variety of diseases. Aims: The aim of this study was to evaluate the efficacy of topical turmeric cream on vitiligo's lesion appearance including size and repigmentation. Patients/Methods: Following the screening, 30 patients were enrolled according to inclusion criteria. The patients received training to apply turmeric and placebo cream at the specified side of their body twice a day for 4 months. Patients were evaluated at the baseline and at monthly intervals to access possible side effects. Lesion size, vitiligo area scoring index (VASI), vitiligo noticeability scale (VNS), and physician global assessment (PGA) were evaluated at the baseline and after four months to compare the changes induced by turmeric and placebo cream. Results: Twenty‐four patients completed the trial. Applying turmeric cream reduced the size of lesions and improved lesion's appearance significantly compared to the placebo group (p < 0.001), and also, patient's satisfaction score was higher following applying turmeric cream compared to placebo (p < 0.05). Conclusions: Turmeric cream can be used as an alternative remedy or adjuvant therapy in mild to moderate vitiligo lesions and in those who cannot tolerate the adverse effects of conventional therapies. [ABSTRACT FROM AUTHOR]

Tapinarof is a novel topical formulation approved recently, in May 2022, by the United States Food and Drug Administration to treat plaque psoriasis. Existing topical therapies for psoriasis are limited by systemic and local adverse effects, medication cost and repeated administration, thus significantly hampering the compliance of patients to therapy. These limitations can be resolved by tapinarof owing to its better efficacy and favourable safety profile in psoriasis management. Tapinarof was developed with a unique mechanism targeting the aryl hydrocarbon receptor (AhR) involved in inflammation and modulation of skin barrier integrity in inflammatory dermatological disorders such as psoriasis and atopic dermatitis. The efficacy and safety outcomes of tapinarof in psoriasis were justified through the two pivotal clinical trials, namely, PSOARING 1 and PSOARING 2. The common adverse effects observed with tapinarof are folliculitis, contact dermatitis and headache. The literature search was conducted for efficacy and safety of tapinarof in the electronic databases of PubMed and Cochrane using a combination of keywords such as tapinarof, psoriasis and AhR. This review will delineate the molecular mechanisms underlying the action of tapinarof and also summarise the trial data supporting the claim that tapinarof is replacing the existing standard of care in psoriasis management. [ABSTRACT FROM AUTHOR]

Background: Venous, arterial, diabetic and pressure ulcers, collectively known as chronic wounds, negatively impact individuals across psychological, social and financial domains. Chronic wounds can be painful and the nature, frequency and impact of pain can differ depending on wound aetiology, wound state and on numerous patient factors. While systemic pharmaceutical agents have some effect in managing pain, there is a need to examine topical agents applied to the wound bed for pain relief. The objective of this study is to examine and synthesise existing literature on the effectiveness of topical agents in managing pain in venous, diabetic, pressure, arterial and mixed venous/arterial ulcers. Methods: We will use Cochrane Systematic Review methodology to identify and synthesise eligible randomised controlled trials (RCTs) evaluating the effectiveness of topical agents in reducing pain in chronic wounds. Embase, Medline, PubMed, CENTRAL, CINAHL, Scopus and Web of Science will be searched from inception to end of June 2022 without language limits. We will independently extract data on the pharmaceutical agent, participant demographics, aetiology, condition of the wound, and type, nature and frequency of pain using a pre-designed data extraction form. Subgroup and sensitivity analysis will be performed to address heterogeneity across studies if appropriate. Further stratification and analyses will be based on included study variables and outcomes. Discussion: Wound pain is primarily managed via systemic pharmaceutical agents. However, patients express reluctance regarding systemic analgesic drugs, fearing addiction. Additionally, persons with chronic wounds have co-morbidities including hypertension, diabetes, or cardiovascular disease and are already taking multiple medications. Topical analgesia can potentially mitigate some of the perceived disadvantages of systemic agents but the available range of these agents and their effectiveness in managing pain in chronic wounds is not so well understood. This review will focus on such agents across a range of the most common chronic wounds.

Background: A novel self-assembling peptide (SAP) can be applied to the post-endoscopic mucosal resection (EMR) defect to treat oozing bleedings. It has been suggested to stimulate early healing of damaged vessels. We hypothesized that SAP application could prevent delayed bleeding (DB) after EMR and performed a prospective cohort study to determine feasibility and safety.Methods: A total of 48 consecutive patients who underwent EMR between June 2018 and August 2019 for large lesions in the esophagus, duodenum (> 1 cm) or colorectum (> 2 cm) were treated with adjuvant SAP application. Duration and ease of SAP application were measured, as well as DB outcome.Results: The EMR defects of 48 patients were treated with SAP; 17 in the esophagus, 13 in the duodenum and 18 in the colorectum. SAP was easy to apply on the EMR defect with a median duration of 2.0 min. A dose of 3 cc was generally enough to cover a defect between 10 and 50 mm. An exploratory analysis of the prophylactic ability of SAP showed that 15.9% of patients (7/44) treated with SAP still had a DB, mostly in the duodenum (4/11). No adverse events related to gel exposure were reported.Conclusions: SAP application after EMR was found to be feasible and safe, and did not delay the procedure; however, DB was still relatively common. Future comparative studies are needed to evaluate whether SAP is able to reduce DB after EMR, particularly for lesions with an increased bleeding risk, such as in the duodenum. [ABSTRACT FROM AUTHOR]

The emergence of multidrug-resistant bacteria constitutes a significant public health issue worldwide. Consequently, there is an urgent clinical need for novel treatment solutions. It has been shown in vitro that phenothiazines can act as adjuvants to antibiotics whereby the minimum inhibitory concentration (MIC) of the antibiotic is decreased. However, phenothiazines do not perform well in vivo, most likely because they can permeate the blood-brain (BBB) barrier and cause severe side-effects to the central nervous system. Therefore, the aim of this study was to synthesize a promazine derivate that would not cross the BBB but retain its properties as antimicrobial helper compound. Surprisingly, in vitro studies showed that the novel compound, JBC 1847 exhibited highly increased antimicrobial activity against eight Gram-positive pathogens (MIC, 0.5–2 mg/L), whereas a disc diffusion assay indicated that the properties as an adjuvant were lost. JBC 1847 showed significant (P < 0.0001) activity against a Staphylococcus aureus strain compared with the vehicle, in an in vivo wound infection model. However, both in vitro and in silico analyses showed that JBC 1847 possesses strong affinity for human plasma proteins and an Ames test showed that generally, it is a non-mutagenic compound. Finally, in silico predictions suggested that the compound was not prone to pass the BBB and had a suitable permeability to the skin. In conclusion, JBC 1847 is therefore suggested to hold potential as a novel topical agent for the clinical treatment of S. aureus skin and soft tissue infections, but pharmacokinetics and pharmacodynamics need to be further investigated.

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Brimonidine is a first-line topical medication for increased intraocular pressure and glaucoma which may be used alone or in conjunction with other topical therapies. Its structural and pharmacological comparabilities to clonidine give way to the hypothesis that it may cause neuropsychiatric side effects. The majority of case reports citing brimonidine toxicity, either for topical or peripheral exposure, include pediatric age groups but especially infants. Among the latter, a dose-response phenomenon is evident. Dose-response correlates have also been shown among adults. Case series and prospective double-blind treatment studies also give evidence for the occurrence of several central nervous system adverse reactions. Topical ophthalmic brimonidine use should be followed for the occurrence of neuropsychiatric disturbances generally, and enhanced vigilance should be maintained for at-risk populations. [ABSTRACT FROM AUTHOR]

Severe hemorrhage causes significant metabolic and cellular dysfunction secondary to deficient tissue perfusion and oxygen delivery. If bleeding continues, hemodynamic destabilization, hypoxemia, multiple organ failure, and death will occur. Techniques employed to promote hemostasis include surgical suture ligatures, cautery, chemical agents, self-assembling nanoparticles, and physical methods, like mechanical pressure. Improved understanding of the natural clotting cascade has allowed newly designed agents to become more targeted for clinical and military use. Topically-applied hemostatic agents have enormous clinical applications in achieving hemostasis. This manuscript describes currently available and developing topical hemostatic materials, including topical active agents, mechanical agents, synthetic/hemisynthetic hemostatic agents, and external hemostatic dressings for clinical practice. [ABSTRACT FROM AUTHOR]

The emergence of multidrug-resistant bacteria constitutes a significant public health issue worldwide. Consequently, there is an urgent clinical need for novel treatment solutions. It has been shown in vitro that phenothiazines can act as adjuvants to antibiotics whereby the minimum inhibitory concentration (MIC) of the antibiotic is decreased. However, phenothiazines do not perform well in vivo , most likely because they can permeate the blood-brain (BBB) barrier and cause severe side-effects to the central nervous system. Therefore, the aim of this study was to synthesize a promazine derivate that would not cross the BBB but retain its properties as antimicrobial helper compound. Surprisingly, in vitro studies showed that the novel compound, JBC 1847 exhibited highly increased antimicrobial activity against eight Gram-positive pathogens (MIC, 0.5–2 mg/L), whereas a disc diffusion assay indicated that the properties as an adjuvant were lost. JBC 1847 showed significant (P < 0.0001) activity against a Staphylococcus aureus strain compared with the vehicle, in an in vivo wound infection model. However, both in vitro and in silico analyses showed that JBC 1847 possesses strong affinity for human plasma proteins and an Ames test showed that generally, it is a non-mutagenic compound. Finally, in silico predictions suggested that the compound was not prone to pass the BBB and had a suitable permeability to the skin. In conclusion, JBC 1847 is therefore suggested to hold potential as a novel topical agent for the clinical treatment of S. aureus skin and soft tissue infections, but pharmacokinetics and pharmacodynamics need to be further investigated. [ABSTRACT FROM AUTHOR]

Objectives: Clinicians have increasingly adopted the widespread use of topical agents to manage chronic wound infections, despite limited data on their effectiveness in vivo. This study sought to evaluate the evidence for commonly employed topical agents used in wounds for the purpose of treating chronic infections caused by biofilm.Method: We included in vitro, animal and human in vivo studies where topical agents were tested for their efficacy against biofilms, for use in wound care. For human studies, we only included those which utilised appropriate identification techniques for visualising and confirming the presence of biofilms.Result: A total of 640 articles were identified, with 43 included after meeting eligibility. In vitro testing accounted for 90% (n = 39) of all included studies, five studies using animal models and three human in vivo studies. Sixteen different laboratory models were utilised, with the most frequent being the minimum biofilm eradication concentration (MBEC™) / well plate assay (38%, n = 15 of 39). A total of 44 commercially available topical agents were grouped into twelve categories with the most commonly tested agents being silver, iodine and polyhexamethylene biguanide (PHMB). In vitro results on efficacy demonstrated iodine as having the highest mean log10 reductions of all agents (4.81, ±3.14).Conclusion: There is large disparity in the translation of laboratory studies to researchers undertaking human trials relating to the effectiveness of commercially available topical agents. There is insufficient human in vivo evidence to definitively recommend any commercially available topical agent over another for the treatment of chronic wound biofilms. The heterogeneity identified between study designs (in vitro to in vivo) further limits the generalisability of results. [ABSTRACT FROM AUTHOR]

Timolol is a commonly-used topical antiglaucoma medication and has proven to be highly efficacious for most recipients. Among the reported adverse events, the neuropsychiatric spectrum has been cited, albeit for a small proportion of those treated. This review summarizes the cumulative published experience of such side effects and assesses the quality of evidence. As for other beta-blockers, whether orally or topically administered, various central nervous systems dysfunctions have been detailed in either case reports or larger patient series. The adverse event commonly resolves following drug termination. Rigorous and more definitive studies of causation are lacking, and to some, such paucity has reduced the belief of a cause and effect relationship. Until otherwise proven, deference should be afforded to the potential for topical timolol to cause neuropsychiatric side effects, and at-risk patients should be closely monitored when they are prescribed this pharmacological agent. [ABSTRACT FROM AUTHOR]

Background: Manuka honey (MH) has significant antibiofilm activity in vitro and in vivo against Staphylococcus aureus, methicillin‐resistant S aureus (MRSA), and Pseudomonas aeruginosa. This is the first randomized, single‐blinded, placebo‐controlled phase 1 clinical trial investigating the safety and preliminary efficacy of MH with augmented methylglyoxal (MGO) rinses in recalcitrant chronic rhinosinusitis (CRS). Methods: Patients were included after previously undergoing endoscopic sinus surgery and presenting with signs and symptoms of sinus infection with positive bacterial cultures on sinus swabs. Patients were randomized to receive 14 days of twice‐daily 16.5% MH + 1.3 mg/mL MGO sinonasal rinses and concurrent 10 days of placebo tablets (MH), or 14 days of twice‐daily saline sinonasal rinses and concurrent 10 days of culture‐directed antibiotic therapy (CON). Safety observations included the University of Pennsylvania Smell Identification Test (UPSIT) and adverse‐event (AE) reporting. Efficacy was assessed comparing microbiology results, Lund‐Kennedy scores (LKSs), and symptom scores using the visual analog scale (VAS) and 22‐item Sino‐Nasal Outcome Test (SNOT‐22). Results: Twenty‐five patients completed the study. MH demonstrated a good safety profile with no major AEs and no changes in UPSIT. Six of 10 (60%) MH patients had a reduction in bacterial culture rate with 1 of 10 of those having negative cultures, compared with 12 of 15 (80%) in the control group with 7 of 15 having negative cultures upon completion of the study. Conclusion: This study concludes that twice‐daily 16.5% MH augmented with 1.3 mg/mL MGO sinonasal rinses alone for 14 days is safe but not superior to culture‐directed oral antibiotics and twice‐daily saline rinses. [ABSTRACT FROM AUTHOR]

Summary: Background: Melasma is an acquired hyperpigmentation, often involving the face, and a source of distress for the affected individuals. Although treatment is challenging and frequently a multimodality approach, topical applications are the mainstay of therapy. Objective: Due to the frequent relapses, a therapy both acting rapidly and suitable for long‐term use, with fewer adverse effects should be administered. In our outpatient clinic, we treated the melasma patients with a previously unreported triple combination which was empirically formulated with lesser amount of active components, regarding the balance between long‐term use and safety. Methods: Sixty‐eight female patients with melasma who referred to our hospital dermatology clinic in the years 2016‐2017 were retrospectively recruited. They all had completed 6‐month treatment with a prescribed cream mixture comprised of azelaic acid (4%), hydroquinone (1.6%), methylprednisolone aceponate (0.04%), and salicylic acid (2%). The outcomes were evaluated both instrumentally (Melanin Index/MI) and by patients (Patient Self‐Assessment Scale/PSAS). Results: Adverse effects declared by the patients were transient irritation in three and mild hypertrichosis in two. Both the MI and PSAS values were found extremely significant at the end of 6th month, compared with initial values. Approximately 62% of total decrease in MI was realized in the first 3 months. Conclusion: The triple combination containing active ingredients with lesser concentrations than proposed, and with the addition of 2% salicylic acid, may be promising as a quite effective and safe protocol in treatment of melasma for longer durations. [ABSTRACT FROM AUTHOR]

Suspected pediatric ingestions of greater than or equal to one teaspoon topical salicylate analgesic are recommended by poison control centers to be managed at healthcare facilities. This cutoff is applied for both liquid and non-liquid (cream, ointment, gel) formulations. California poison control cases involving topical salicylate exposures in children less than 6-years-old who were evaluated at a health care facility between 2003 and 2018 were analyzed. Of 599 patient cases, the majority described no or minor symptoms, with gastrointestinal distress being the most common. Signs of salicylate toxicity (metabolic acidosis, tachypnea) occurred in six cases. Seven patients were hospitalized, six of whom were exposed to liquid preparations. In line with previous research, liquid salicylate preparations were more frequently associated with the signs of salicylate toxicity and hospitalization. There was a low frequency of severe side effects and low hospitalization rates among those referred to a healthcare facility, especially for non-liquid topical salicylate ingestions. [ABSTRACT FROM AUTHOR]

Background: Acetyl hexapeptide-8, also known as Argireline, is a topical, short-acting, synthetic peptide that has recently gained popularity for its antiwrinkle effects. This agent has emerged as a more accessible alternative to botulinum neurotoxin., Objective: This study evaluates the public interest in acetyl hexapeptide-8 in the United States from 2013 to 2023, as described by search volume on Google, the most-used search engine., Methods: We analyzed the longitudinal relative monthly search volume from January 1, 2013, to January 1, 2023, for acetyl hexapeptide-related terms. We compared the internet search trends for "Botox" during this period to "Argireline.", Results: The terms "Argireline" and "Botox in a Bottle" both had substantial increases in search volume in 2022. Although its search volume is drastically increasing, "Argireline" was less searched than "Botox," which had a stable, up-trending search volume over the past decade., Conclusions: The increasing interest in acetyl hexapeptide-8 may be due to its cost-effectiveness and use as a botulinum neurotoxin alternative. Affordability, over-the-counter availability, and ease of self-application of the agent suggest its potential to enhance accessibility to cosmetic dermatologic care., (©Sofia Eva Olsson, Bhavana Sreepad, Trevor Lee, Manal Fasih, Arman Fijany. Originally published in JMIR Dermatology (http://derma.jmir.org), 20.02.2024.)

Although modern biologics targeting different inflammatory mediators show promising therapeutic success, comprehensive knowledge about the molecular events in psoriatic keratinocytes that contribute to the pathogenesis and could serve as therapeutic targets is still scarce. However, recent efforts to understand the deregulated signal transduction pathways have led to the development of small molecule inhibitors e.g., tofacitinib targeting the Jak/Stat cascade that opens additional therapeutic options. Recently, the PI3-K/Akt/mTOR signaling pathway has emerged as an important player in the control of epidermal homeostasis. This review summarizes the current knowledge on the role of this pathway in the pathogenesis of psoriasis, especially the epidermal manifestation of the disease and discusses current approaches to target the pathway therapeutically.

Background: The management of recalcitrant chronic rhinosinusitis (CRS) is challenged by difficult-to-treat polymicrobial biofilms and multidrug resistant bacteria. This has led to the search for broad-spectrum non-antibiotic antimicrobial therapies. Colloidal silver (CS) has significant antibiofilm activity in vitro and in vivo against S. aureus, MRSA, and P. aeruginosa. However, due to the lack of scientific efficacy, it is only currently used as an alternative medicine. This is the first study looking at the safety and efficacy of CS in recalcitrant CRS.Methods: Patients were included when they had previously undergone endoscopic sinus surgery and presented with signs and symptoms of sinus infection with positive bacterial cultures. Twenty-two patients completed the study. Patients were allocated to 10–14 days of culture directed oral antibiotics with twice daily saline rinses (n = 11) or 10 days of twice daily 0.015 mg/mL CS rinses (n = 11). Safety observations included pre- and post-treatment serum silver levels, University of Pennsylvania Smell Identification Test (UPSIT) and adverse event (AE) reporting. Efficacy was assessed comparing microbiology results, Lund Kennedy Scores (LKS) and symptom scores using Visual Analog Scale (VAS) and Sino-Nasal Outcome Test (SNOT-22).Results: CS demonstrated good safety profile with no major adverse events, no changes in UPSIT and transient serum silver level changes in 4 patients. CS patients had 1/11 (9.09%) negative cultures, compared to 2/11 (18.18%) in the control group upon completion of the study. Whilst not statistically significant, both groups showed similar improvement in symptoms and endoscopic scores.Conclusion: This study concludes that twice daily CS (0.015 mg/mL) sinonasal rinses for 10 days is safe but not superior to culture-directed oral antibiotics. Further studies including more patients and looking at longer treatment or improving the tonicity of the solution for better tolerability should be explored.

Introduction Scabies is a highly contagious skin disease caused by an ectoparasite mite called Sarcoptes scabiei . Ivermectin and permethrin have been commonly used for the treatment of scabies. However, topical ivermectin has been compared to other treatment modalities to a lesser extent. Objective This study aimed to compare the efficacy of topical ivermectin versus topical permethrin in the treatment of uncomplicated scabies. Methods 354 patients with scabies attending the dermatology outpatient department of Pak Emirates Military Hospital Rawalpindi were enrolled. Patients were divided into two groups randomly. The first group and their family contacts received 1% ivermectin lotion whereas the other received 5% permethrin lotion. Patients were evaluated at the end of the second and the fourth week. Results At the end of the second week, initial follow-up showed that 97 out of 159 patients (61.0%) in the ivermectin 1% group, and 107 out of 159 patients (67.3%) in the permethrin 5% group had achieved clinical cure (P=0.24). On the final follow-up at the end of Week 4, the cure rate amounted to 85.5% (136 of 159 patients) in the ivermectin group and 89.9% (143 of 159 patients) in the permethrin group. Differences among both groups remained statistically insignificant (P=0.23). Conclusions The use of ivermectin 1% versus permethrin 5% as topical therapy showed almost identical results for the treatment of uncomplicated scabies. Side effects were minimal and there were no significant differences observed in patients with regard to compliance among both the groups., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Saeed et al.)

Although modern biologics targeting different inflammatory mediators show promising therapeutic success, comprehensive knowledge about the molecular events in psoriatic keratinocytes that contribute to the pathogenesis and could serve as therapeutic targets is still scarce. However, recent efforts to understand the deregulated signal transduction pathways have led to the development of small molecule inhibitors e.g., tofacitinib targeting the Jak/Stat cascade that opens additional therapeutic options. Recently, the PI3-K/Akt/mTOR signaling pathway has emerged as an important player in the control of epidermal homeostasis. This review summarizes the current knowledge on the role of this pathway in the pathogenesis of psoriasis, especially the epidermal manifestation of the disease and discusses current approaches to target the pathway therapeutically. [ABSTRACT FROM AUTHOR]

The neuropeptide substance P (SP) is known to stimulate wound healing by regulating the production of relevant cytokines as well as cell proliferation and migration. However, the therapeutic application of SP is limited by its low stability under biological conditions and oxidation during purification, formulation, and storage. To address this problem, we developed a novel formulation of SP as an SP gel, and investigated its wound healing activity both in vitro and in vivo. SP in SP gel was stable at various temperatures for up to 4 weeks. In vitro, SP gel exhibited more potential as a candidate wound-healing agent than SP alone, as evidenced by the observed increases in the proliferation and migration of human epidermal keratinocytes and human dermal fibroblasts. In vivo experiments showed that SP gel treatment enhanced the healing of full-thickness wounds in mice as compared to SP alone. These results demonstrate the benefits of SP gel as a promising topical agent for wound treatment. [ABSTRACT FROM AUTHOR]

Background: The management of recalcitrant chronic rhinosinusitis (CRS) is challenged by difficult-to-treat polymicrobial biofilms and multidrug resistant bacteria. This has led to the search for broad-spectrum non-antibiotic antimicrobial therapies. Colloidal silver (CS) has significant antibiofilm activity in vitro and in vivo against S. aureus, MRSA, and P. aeruginosa. However, due to the lack of scientific efficacy, it is only currently used as an alternative medicine. This is the first study looking at the safety and efficacy of CS in recalcitrant CRS. Methods: Patients were included when they had previously undergone endoscopic sinus surgery and presented with signs and symptoms of sinus infection with positive bacterial cultures. Twenty-two patients completed the study. Patients were allocated to 10-14 days of culture directed oral antibiotics with twice daily saline rinses (n = 11) or 10 days of twice daily 0.015 mg/mL CS rinses (n = 11). Safety observations included pre- and post-treatment serum silver levels, University of Pennsylvania Smell Identification Test (UPSIT) and adverse event (AE) reporting. Efficacy was assessed comparing microbiology results, Lund Kennedy Scores (LKS) and symptom scores using Visual Analog Scale (VAS) and Sino-Nasal Outcome Test (SNOT-22). Results: CS demonstrated good safety profile with no major adverse events, no changes in UPSIT and transient serum silver level changes in 4 patients. CS patients had 1/11 (9.09%) negative cultures, compared to 2/11 (18.18%) in the control group upon completion of the study. Whilst not statistically significant, both groups showed similar improvement in symptoms and endoscopic scores. Conclusion: This study concludes that twice daily CS (0.015 mg/mL) sinonasal rinses for 10 days is safe but not superior to culture-directed oral antibiotics. Further studies including more patients and looking at longer treatment or improving the tonicity of the solution for better tolerability should be explored. [ABSTRACT FROM AUTHOR]

In particular, neuropathic pain is a major form of chronic pain. This type of pain results from dysfunction or lesions in the central and peripheral nervous system. Capsaicin has been traditionally utilized as a medicine to remedy pain. However, the effectiveness and safety of this practice is still elusive. Therefore, this systematic review aimed to investigate the effect of topical capsaicin as a pain-relieving agent that is frequently used in pain management. In brief, all the double-blinded, randomized placebo- or vehiclecontrolled trials that were published in English addressing postherpetic neuralgia were included. Meta-analysis was performed using Revman R version 5.3. Upon application of the inclusion and exclusion criteria, only six trials fulfilled all the criteria and were included in the review for qualitative analysis. The difference in mean percentage change in numeric pain rating scale score ranges from -31 to -4.3. This demonstrated high efficacy of topical capsaicin application and implies that capsaicin could result in pain reduction. Furthermore, meta-analysis was performed on five of the included studies. All the results of studies are in favor of the treatment using capsaicin. The incidence of side effects from using topical capsaicin is consistently higher in all included studies, but the significance of safety data cannot be quantified due to a lack of p-values in the original studies. Nevertheless, topical capsaicin is a promising treatment option for specific patient groups or certain neuropathic pain conditions such as postherpetic neuralgia. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a common chronic relapsing inflammatory skin disease. The pathogenesis of AD is complex and still not fully understood. Despite recent therapeutic developments, the current therapeutic arsenal of AD remains limited and is associated with long-term efficacy and safety issues. Therefore, new topical therapies with different mechanisms of action are required to overcome the limitations of existing treatments. Difamilast is a phosphodiesterase 4 inhibitor currently in phase 3 studies. Difamilast shows antipruritic and anti-inflammatory properties and a rapid onset of action, with significant differences in some parameters from the vehicle within 1 week of treatment. Phase 2 and 3 clinical trials have shown that difamilast ointments are effective and well tolerated in adult and pediatric patients with AD, and are expected to be used for long-term AD treatment. In 2021, difamilast was the first phosphodiesterase 4inhibitor to acquire manufacturing and marketing approval in Japan for the treatment of adult and pediatric patients (2 years of age and older) with AD. This article is a narrative review of the current literature on difamilast in the management of AD.

Topical medicinal patches have been popular for the treatment of minor injuries like sprains and avulsions. Other inflammatory conditions like chronic musculo-tendinous pain and or fasciitis are also taken care of by local ointments or rubs. In the oriental communities, medicinal herbs frequently form the major components of the patches.In spite of the lack of scientific evidence of efficacy, the popularity of such traditional application persists for centuries.In this era of evidence-based clinical treatment, there is an urgent need to look into this traditional practice. The purpose should include a scientific verification of the efficacy of the practice, and once proven, further explorations would be indicated to bring the practice to a higher level.A system of comprehensive exploration was proposed and practiced in the past years to fulfill the aspiration. The research consisted of four areas:(1)Identification of the suitable medicinal herbs for the topical study;(2)Study of the biological activities of the selected herbs, concentrating on the areas of anti-inflammation, anti-oxidation, angiogenesis and cellular proliferation;(3)Study on the transcutaneous transport of the chemicals of the selected herbs to deeper tissues; and(4)Pilot clinical studies on common superficial inflammatory musculo-skeletal conditions to give objective clinical evidences to the topical applications.Five herbs were identified as suitable candidates of study. They were put into relevant laboratory platforms and were proven to be anti-oxidant, anti-inflammatory and pro-angiogenic. Three of the herbs were prepared as topical patches with an enhancer and used to treat three common ailments in pilot clinical trials, viz., plantar fasciitis, undisplaced metatarsal fracture and tendonitis of the wrist (de-Quervain’s disease) and the elbow (Tennis elbow). The clinical results of the pilot studies were very positive.It is therefore concluded that further explorations are justified to create medicinal herb patches of even greater efficacy.

The rising prevalence of diabetes mellitus brings with it a rise in the occurrence of several complications of the disease such as chronic non-healing wounds. Diabetics are more prone to developing chronic wounds due to complications like peripheral neuropathy, poor foot care, hyperglycaemia and peripheral vascular diseases. The aim of this review is to discuss the various imbalances in the cytokine environment of diabetic wounds and to explore the developments in their management with an emphasis on agents that may be used topically to aid the healing process of chronic wounds. A systematic search was conducted on Scopus, PubMed and Google Scholar and relevant articles were shortlisted. We conclude that increased blood sugar impairs most phases of wound healing in several ways. Supplementary therapy with either topical or systemic cytokines is shown to promote wound healing in a diabetic wound., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Rangwala et al.)

Background: The factors influencing the use of topical agents in combination with biologic therapies for the treatment of plaque psoriasis (PsO) are not well understood. Objective: To examine potential predictors of topical use in patients with moderate to severe plaque PsO receiving etanercept (ETN). Methods: Post hoc descriptive analyses and a multinomial regression of the REFINE study data were used to examine associations between topical agent potency and covariates, including Psoriasis Area and Severity Index (PASI) score, study site, and province. Results: Not achieving PASI 90 at week 12 predicted topical use, with a lower PASI 90 rate in patients who used highpotency topical agents post randomization (P = .003). Additionally, statistically significant differences were found in patterns of topical use among Canadian provinces (P = .007), with the use of high-potency topical agents being greater in Ontario and Quebec than the rest of Canada. Conclusion: This analysis revealed that region and PASI 90 status at week 12 predict topical use. [ABSTRACT FROM AUTHOR]

Topical medicinal patches have been popular for the treatment of minor injuries like sprains and avulsions. Other inflammatory conditions like chronic musculo-tendinous pain and or fasciitis are also taken care of by local ointments or rubs. In the oriental communities, medicinal herbs frequently form the major components of the patches. In spite of the lack of scientific evidence of efficacy, the popularity of such traditional application persists for centuries. In this era of evidence-based clinical treatment, there is an urgent need to look into this traditional practice. The purpose should include a scientific verification of the efficacy of the practice, and once proven, further explorations would be indicated to bring the practice to a higher level. A system of comprehensive exploration was proposed and practiced in the past years to fulfill the aspiration. The research consisted of four areas: (1) Identification of the suitable medicinal herbs for the topical study; (2) Study of the biological activities of the selected herbs, concentrating on the areas of anti-inflammation, anti-oxidation, angiogenesis and cellular proliferation; (3) Study on the transcutaneous transport of the chemicals of the selected herbs to deeper tissues; and (4) Pilot clinical studies on common superficial inflammatory musculo-skeletal conditions to give objective clinical evidences to the topical applications. Five herbs were identified as suitable candidates of study. They were put into relevant laboratory platforms and were proven to be anti-oxidant, anti-inflammatory and proangiogenic. Three of the herbs were prepared as topical patches with an enhancer and used to treat three common ailments in pilot clinical trials, viz., plantar fasciitis, undisplaced metatarsal fracture and tendonitis of the wrist (de-Quervain's disease) and the elbow (Tennis elbow). The clinical results of the pilot studies were very positive. It is therefore concluded that further explorations are justified to create medicinal herb patches of even greater efficacy. [ABSTRACT FROM AUTHOR]