Mission impossible: Dermal delivery of growth factors via microneedling.

The clinical application of transdermal delivery has been limited to lipophilic drugs with a molecular weight of less than 500 Da. The development of polymeric microneedles enabled the transdermal delivery of larger proteins and drugs. Extensive research has been conducted on the molecular size, solubility, pH, concentration, and polarity of transdermal delivery; however, the maximal molecular weight for transdermal microneedle delivery has not been established. Clinicians often use simple microneedles to deliver high molecular weight growth factors of platelet-rich plasma across the skin; thus, we set out to explore the feasibility of delivering growth factors through microneedling. In this communication, we present histological evidence that microneedling do not enhance transdermal delivery of growth factors and thus provide no clinical benefit.

Frontal pattern hair loss among Chinese women is frequently associated with ponytail hairstyle.

Female alopecia patients in China often present with a frontal pattern hair loss. This feature is seen less frequently in western women. Women in China frequently style their hair in a ponytail. Thus, we hypothesized that the high prevalence of frontal pattern hair loss in Chinese women is due to traction alopecia. To better understand this, we studied 43 women presenting frontal alopecia at a hair clinic. Among the women presenting frontal alopecia, 79% reported styling their hair in a ponytail four or more days per week for an average period of 10 years. To our knowledge, this is the first study to elucidate the cause of frequent frontal alopecia in Chinese women. Although cultural style changes are difficult to change, we believe that awareness of the medical implications of frequent ponytail styling will reduce the rate of frontal alopecia among Chinese women.

Tretinoin enhances minoxidil response in androgenetic alopecia patients by upregulating follicular sulfotransferase enzymes.

Minoxidil sulfate is the active metabolite required to exert the vasodilatory and hair growing effects of minoxidil. For hair growth, sulfotransferase enzymes expressed in outer root sheath of the hair follicle sulfonate minoxidil. The large intra-subject variability in follicular sulfotransferase was found to predict minoxidil response and thus explain the low response rate to topical minoxidil in the treatment of androgenetic alopecia. A method to increase minoxidil response would be of significant clinical utility. Retinoids have been reported to increase minoxidil response. The purported mechanism of action was retinoid modulation of skin permeation to minoxidil; however, evidence to the contrary supports retinoids increase dermal thickness. In order to elucidate the effect of topical retinoids on minoxidil response, we studied the effect of topical tretinoin on follicular sulfotransferase. In this study, we demonstrate that topical tretinoin application influences the expression of follicular sulfotransferase. Of clinical significance, in our cohort, 43% of subjects initially predicted to be nonresponders to minoxidil were converted to responders following 5 days of topical tretinoin application. To the best of our knowledge, this is the first study to elucidate the interaction mechanism between topical minoxidil and retinoids and thus provides a pathway for the development of future androgenetic alopecia treatments.

Styling without shedding: Novel topical formula reduces hair shedding by contracting the arrector pili muscle.

Approximately 40% of women experience excessive hair shedding during styling (e.g., hair brushing). Previously, we demonstrated that topically applied phenylephrine, a potent α1 adrenergic receptor agonist, can be used to contract the arrector pili muscle of the follicular unit; thus, increasing the force required to pluck hair and reducing shedding during brushing. While demonstrating efficacy, phenylephrine has several drawbacks when applied to the scalp, including the possibility cardiovascular events. We hypothesized that a high concentration of a weak α1 agonist would allow for: (a) rapid penetration through the stratum corneum eliciting a quick response; (b) a low probability of cardiac adverse events owing to the low receptor binding affinity; and (c) an efficacy of the weak α1 agonist similar to that of phenylephrine at the local site of application. Accordingly, we developed a novel topical solution, AB-102, containing a high concentration of a weak α1 agonist. Several studies were conducted to test the safety and efficacy of AB-102. In a dose escalating safety study, utilizing a wearable holter monitor, we observed no cardiac or hemodynamic adverse events. In addition, in a controlled efficacy study, AB-102 reduced the number of hairs shed during brushing by up to 77% (average of 38%).

Characterization of follicular minoxidil sulfotransferase activity in a cohort of pattern hair loss patients from the Indian Subcontinent.

Several studies have established that sulfotransferase enzyme activity in the outer root sheath of plucked hair follicles predicts response to topical minoxidil in the treatment of pattern hair loss. However, the prevalence of this enzyme activity among Indian patients has not been studied. Additionally, no reports in the literature characterize sulfotransferase activity based on sex, age, duration of hair loss, grade of hair loss, and family history. In this study we utilized a sulfotransferase activity assay first reported by Goren et al. We characterize the follicular sulfotransferase activity of 120 pattern hair loss patients visiting a dermatology outpatient clinic in India. Overall, 40.8% of patients with pattern hair loss had low levels of sulfotransferase. Surprisingly, 49.3% of men had low levels of sulfotransferase compared to 26.6% of women. No correlation was found between sulfotransferase activity and age, duration of hair loss, grade of hair loss, or family history. A sub-analysis of patient reported outcomes (PRO) validated previous findings that sulfotransferase enzyme activity is a predictive marker for minoxidil response in pattern hair loss patients.

Prevalence of hair shedding among women.

Hair shedding in female patients is a frequent complaint in dermatological, endocrinological, and gynecological consults. Previously, the Sinclair Hair Shedding Scale was developed to assess normal versus excessive hair shedding in female pattern hair loss (FPHL) subjects. However, the prevalence of hair shedding in females not suffering from FPHL is unknown. To gain better understanding of hair shedding in the general population, we recruited 300 subjects visiting a public hospital for conditions other than alopecia. Of the 300 subjects recruited, 263 did not suffer from FPHL. Among those subjects, approximately 40% reported experiencing excessive hair shedding (as defined by the Sinclair Hair Shedding Scale) on hair washing days. In comparison, in our subject population, approximately 60% of subjects with FPHL reported excessive hair shedding on hair washing days. To best of our knowledge, this is the first study to quantify the prevalence of hair shedding in women. While, no treatment currently exists for this condition, we hope that this study would encourage physicians and researchers to address this frequent concern.

α1 -AR agonist induced piloerection protects against the development of traction alopecia.

Traction alopecia is hair loss that occurs after persistent pulling (e.g., during cosmetic procedures) on the roots of hair over time. Unlike plucking, which is painful, persistent pulling may go unnoticed until a patient presents with either bald spots or diffuse telogen shedding. Each hair follicle in the scalp contains an arrector pili muscle that, when contracted, erects the hair. The smooth muscle in the arrector pili expresses α1 adrenergic receptors (α1 -AR). As such, we hypothesized that contraction of the arrector pili muscle via an α1 -AR agonist would increase the threshold of force required to pluck hair during cosmetic procedures. Female subjects, ages 18-40, were recruited to study the effect of topically applied phenylephrine, a selective α1 -AR agonist, on epilation force and hair shedding during cosmetic procedures. In our blinded study, 80% of subjects demonstrated reduced shedding on days using phenylephrine compared to days using a placebo solution. The average reduction in hair loss was approximately 42%. In addition, the force threshold required for epilation increased by approximately 172% following topical phenylephrine application. To our knowledge this is the first study demonstrating the utility of α1 -AR agonists in the treatment of traction alopecia and hair shedding during cosmetic procedures.

Combined therapy for resistant vitiligo lesions: NB-UVB, microneedling, and topical latanoprost, showed no enhanced efficacy compared to topical latanoprost and NB-UVB.

Vitiligo is depigmenting disorder of the skin and mucous membranes but despite various therapeutic options, complete and satisfactory treatment of vitiligo still remains a challenge. Therapeutic success also varies depending on the localization of lesions; hands and bony prominents are considered to be resistant to treatment. We investigated feasibility of treating resistant bilateral symmetrical vitiligo vulgaris and acrofacialis lesions with combination of narrowband UVB and topical prostaglandins (0.005% latanoprost solution) with or without Dermaroller 0.5 mm needle length-assisted microneedling. Frequency of repigmentation onset was generally low (37.8%) and pronounced repigmentation was infrequently seen (26-50% repigmentation in 20.8%, and >50% repigmentation in only 8.8% of repigmenting lesions). Our study, however, showed that latanoprost can be used in combination with NB-UVB phototherapy to induce repigmentation in some vitiligo lesions in resistant-to-treatment location, while addition of skin microneedling seems not to improve the treatment outcome and possibly needs modification.

Management of chronic pruritus with a UV filtering topical cream.

Chronic pruritus is a common dermatological condition affecting 10-13% of the general population. UVB phototherapy has been demonstrated to be effective in relieving the symptoms of pruritus. However, phototherapy is rarely administered because the treatment is time-consuming and expensive, when compared to other topical drugs. In previous works, it has been reported that a topical cream, which selectively filters solar UVB can be used as a convenient alternative to traditional phototherapy. Here, we report the results of a pilot study aimed at assessing the effectiveness of the cream for treating pruritus. Seven patients with pruritus symptoms were included in the study. After 3 months of treatment (3 sessions per week), all patients noted improvement in pruritus symptoms. These preliminary results demonstrate that the novel topical cream could provide a convenient, low cost treatment for chronic pruritus patients.

Mixed vitiligo of Blaschko lines: a newly discovered presentation of vitiligo responsive to combination treatment.

Vitiligo, depigmenting disorder of the skin and mucous membranes, affects up to 1% of the population worldwide. It is classified into four major types: segmental, non-segmental, mixed, and unclassified type. Non-segmental vitiligo refers to non-dermatomal distribution of lesions, while dermatomal distribution of lesions is present in patients with segmental vitiligo. Segmental vitiligo can also follow Blaschko lines - pathways of epidermal cell migration and proliferation during the development of the fetus. Here, we present patient with segmental and non-segmental vitiligo following Blaschko lines with excellent therapeutic response to combined therapy. Prior to our report, a case of segmental and non-segmental vitiligo followed by Blaschko lines was never described, therefore we suggest the term "mixed vitiligo of Blaschko lines" to describe this entity. This is also a rare case in which 90% repigmentation was achieved in patient with segmental and nonsegmental vitiligo following Blaschko lines in only 2 months of combined therapy.

Irrigation of human prepared root canal--ex vivo based computational fluid dynamics analysis.

AIM: To analyze the influence of the needle type, insertion depth, and irrigant flow rate on irrigant flow pattern, flow velocity, and apical pressure by ex-vivo based endodontic irrigation computational fluid dynamics (CFD) analysis. METHODS: Human upper canine root canal was prepared using rotary files. Contrast fluid was introduced in the root canal and scanned by computed tomography (CT) providing a three-dimensional object that was exported to the computer-assisted design (CAD) software. Two probe points were established in the apical portion of the root canal model for flow velocity and pressure measurement. Three different CAD models of 27G irrigation needles (closed-end side-vented, notched open-end, and bevel open-end) were created and placed at 25, 50, 75, and 95% of the working length (WL). Flow rates of 0.05, 0.1, 0.2, 0.3, and 0.4 mL/s were simulated. A total of 60 irrigation simulations were performed by CFD fluid flow solver. RESULTS: Closed-end side-vented needle required insertion depth closer to WL, regarding efficient irrigant replacement, compared to open-end irrigation needle types, which besides increased velocity produced increased irrigant apical pressure. For all irrigation needle types and needle insertion depths, the increase of flow rate was followed by an increased irrigant apical pressure. CONCLUSIONS: The human root canal shape obtained by CT is applicable in the CFD analysis of endodontic irrigation. All the analyzed values -irrigant flow pattern, velocity, and pressure - were influenced by irrigation needle type, as well as needle insertion depth and irrigant flow rate.

SULT1A1 (Minoxidil Sulfotransferase) enzyme booster significantly improves response to topical minoxidil for hair regrowth.

BACKGROUND: Minoxidil is a widely used over-the-counter topical treatment for hair loss. The response rate for topical minoxidil is relatively low. Minoxidil is a pro-drug, converted to its active form, minoxidil sulfate, by SULT1A1 enzymes located in the scalp. Recently, a novel topical formula that increases the activity of SULT1A1 in hair follicles was reported. AIMS: To evaluate any benefit of applying the SULT1A1 enzyme booster prior to daily 5% minoxidil treatment. METHODS: Male androgenic alopecia patients were recruited to a randomized blinded placebo-controlled study. Patients were randomized to receive 5% topical minoxidil plus the novel formula or minoxidil plus a sham adjuvant. Patient's hair growth was monitored using global photography over 60 days. RESULTS: Twenty-four males with androgenic alopecia (Norwood scale average 4.4, range 2-6) were randomized and completed the trial: 12 in the active arm and 12 in placebo. 75% of the subjects who used the SULT1A1 adjuvant with their daily minoxidil treatments for 60 days regrew hair versus 33% of those using the placebo adjuvant (p = 0.023). CONCLUSIONS: In a small cohort of androgenetic alopecia men, adding the SULT1A1 adjuvant to their daily minoxidil treatment regimen improved hair regrowth.

Novel cannabidiol aspartame combination treatment (JW-100) significantly reduces ISGA score in atopic dermatitis: Results from a randomized double-blinded placebo-controlled interventional study.

BACKGROUND: Atopic dermatitis (AD) is a common and chronic inflammatory skin disease that erupts periodically. Although the negative impact of the disorder on overall quality of life has been well established, new treatments for AD are still needed. Various studies have reported on cannabidiol's effectiveness in relieving pain and easing inflammation while not presenting major health risks. AIMS: In this communication, we aim to demonstrate the effectiveness of a novel cannabidiol (CBD) and aspartame formulation, JW-100, in relieving signs and symptoms of AD. PATIENTS/METHODS: We conducted a double-blinded placebo-controlled interventional study randomizing patients to one of three treatment groups: JW-100 (CBD plus aspartame), CBD only, or placebo topical formulations. The Investigator's Static Global Assessment (ISGA) score was used to document any changes in AD resulting from the applied interventions at 14 days. RESULTS: Fifty-seven patients completed the trial and were included in the final analysis. The ISGA score of the patients at baseline was 2.56, 2.24, and 2.24, for the JW-100, CBD, and placebo groups, respectively. After two weeks of treatment, the ISGA score reduced by 1.28, 0.81, and 0.71, for the JW-100, CBD, and placebo groups, respectively. The JW-100 cohorts demonstrated statistically significant ISGA score reduction (p = 0.042). 50% of patients in the JW-100 group achieved ISGA score of clear or almost clear (0 or 1) with at least a 2-grade improvement from baseline after treatment (p = 0.028). Only 20% and 15% of patients in the CBD only and placebo groups reported ISGA score of clear or almost clear (0 or 1). CONCLUSIONS: JW-100, a novel topical formulation containing CBD and aspartame, was demonstrated to produce statistically significant improvements in AD following 14 days of topical application.

Novel yeast extract is superior to colloidal oatmeal in providing rapid itch relief.

BACKGROUND: Approximately, 13.5% of the population suffers from chronic itch. Many cosmetic and pharmaceutical treatments for itch are available; however, cosmetic treatments are not reliably effective and most pharmaceutical formulations carry the risk of adverse events with chronic use. AIMS: Previously, we have reported a novel extraction process of Saccharomyces cerevisiae, that is, Baker's yeast. The extract obtained from the novel process demonstrates superior anti-itch properties compared to other yeast extracts. In our previous study, we demonstrated that, after 30 minutes, the extract significantly reduced itch when compared to a placebo lotion (P = .002). METHODS: In the present study we conducted a head-to-head comparison with the leading cosmetic itch product: lotion containing colloidal oatmeal (CO). A randomized double-blinded study of 60 patients was conducted. RESULTS: In our study, the novel yeast extract was vastly superior to the CO containing lotion (Aveeno™ Eczema Therapy Moisturizing Cream). We saw statistically significant difference in the reduction of itch (P = .0001) using the novel yeast extract vs the CO lotion. Additionally, the yeast extract was shown to relieve itch in as little as one minute after application. CONCLUSION: The novel yeast extract rapidly relieves itch and is superior to the cosmetic market leader, CO lotion.

Proxalutamide Reduces the Rate of Hospitalization for COVID-19 Male Outpatients: A Randomized Double-Blinded Placebo-Controlled Trial.

Antiandrogens have demonstrated a protective effect for COVOD-19 patients in observational and interventional studies. The goal of this study was to determine if proxalutamide, an androgen receptor antagonist, could be an effective treatment for men with COVID-19 in an outpatient setting. A randomized, double-blinded, placebo-controlled clinical trial was conducted at two outpatient centers (Brasilia, Brazil). Patients were recruited from October 21 to December 24, 2020 (clinicaltrials.gov number, NCT04446429). Male patients with confirmed COVID-19 but not requiring hospitalization (COVID-19 8-point ordinal scale <3) were administered proxalutamide 200 mg/day or placebo for up to 7 days. The primary endpoint was hospitalization rate at 30 days post-randomization. A total of 268 men were randomized in a 1:1 ratio. 134 patients receiving proxalutamide and 134 receiving placebo were included in the intention-to-treat analysis. The 30-day hospitalization rate was 2.2% in men taking proxalutamide compared to 26% in placebo, P < 0.001. The 30-day hospitalization risk ratio was 0.09; 95% confidence interval (CI) 0.03-0.27. Patients in the proxalutamide arm more frequently reported gastrointestinal adverse events, however, no patient discontinued treatment. In placebo group, 6 patients were lost during follow-up, and 2 patients died from acute respiratory distress syndrome. Here we demonstrate the hospitalization rate in proxalutamide treated men was reduced by 91% compared to usual care.

Novel cannabidiol sunscreen protects keratinocytes and melanocytes against ultraviolet B radiation.

Cannabidiol (CBD), a natural occurring phytocannabinoid, is used extensively in consumer products ranging from foods to shampoos, topical oils and lotions. Several studies demonstrated the anti-inflammatory and antioxidative properties of cannabidiol. Nevertheless, the role of cannabidiol use in sunscreens is largely unknown as no studies on its effect on keratinocytes or melanocytes exist. As such, we aimed to explore the effect of CBD on keratinocyte and melanocyte viability following ultraviolet B (UVB) irradiation. CBD exhibited a dose-dependent protective effect on both keratinocytes and melanocyte viability. Further, since CBD does not demonstrate absorption in the UVB spectra, we speculate that the protective effect is due to reduction in reactive oxygen species. To our knowledge, this is the first study demonstrating the protective effect of CBD on keratinocytes and melanocytes irradiated with UVB.

Novel "After Minoxidil" spray improves topical minoxidil compliance and hair style manageability.

BACKGROUND: Topical minoxidil is the only US FDA-approved drug for the treatment of female pattern hair loss (FPHL). While the safety profile of topical minoxidil is excellent, the efficacy of minoxidil in hair growth is extremely low. A recent survey of 8000 people observed that only 4% of hair loss patients using an over-the-counter minoxidil were very satisfied with their results. In contrast, in clinical studies with an intervening physician, approximately 30%-40% of patients demonstrate an appreciable benefit. Compliance with topical drug regimens is often a major obstacle, limiting their effectiveness. Topical minoxidil leaves a greasy residue on the hair, which is especially problematic for women who do not wash their hair daily. AIMS: We set out to develop an "After Minoxidil" companion spray to minoxidil that removes residual minoxidil from the hair, where it is not needed, yet leaves minoxidil on the scalp where it is required. We hypothesized that improving the cosmetic properties of minoxidil would improve patient compliance with the drug and subsequently improve clinical outcomes. METHODS: A cohort of 20 FPHL patients was recruited to use the novel "After Minoxidil" spray and report changes in hair quality on a Likert scale. RESULTS: In our cohort of FPHL patients, the novel "After Minoxidil" spray restored ease of styling and reduced greasiness to preminoxidil level in 65% and 85% of subjects, respectively. The average reduction in perceived greasiness was 78%. Importantly, 70% of subjects interviewed stated they would likely continue to use the minoxidil and "After Minoxidil" treatment regimen for 6 months, vs 0% willing to use minoxidil alone. CONCLUSION: The novel "After Minoxidil" spray improved ease of hair styling and reduced greasiness following application of topical minoxidil; thus, the novel "After Minoxidil" spray may help improve drug compliance and efficacy.

Yeast extract demonstrates rapid itch relief in chronic pruritus.

BACKGROUND: Pruritus is the most common complaint encountered in dermatological practice. It is estimated that up to 4% of the world population suffers from chronic itch. Chronic pruritus can be associated with both cutaneous or systemic conditions. While a plethora of treatments attempt to address itch, most carry risk of significant adverse events with chronic use; thus, there exists an unmet need to develop safe treatments for chronic pruritus. A recent study demonstrated that a novel extract from Saccharomyces cerevisiae, that is, Baker's yeast, blocks various histamine receptors as well as inhibits numerous inflammatory cytokines. METHODS: Given the long-term safety profile of Baker's yeast, we set to investigate the efficacy of the novel extract in the treatment of chronic pruritus. KEY RESULTS: In our study, we demonstrated that within 30 minutes, the novel extract significantly reduced itch when compared to a placebo lotion (P = .0020). CONCLUSIONS: To our knowledge, this is the first study demonstrating that a novel extract from Saccharomyces cerevisiae can provide rapid and sustained itch relief to chronic pruritus patients.

A preliminary observation: Male pattern hair loss among hospitalized COVID-19 patients in Spain - A potential clue to the role of androgens in COVID-19 severity.

A preliminary observation of high frequency of male pattern hair loss among admitted COVID-19 patients and suggest that androgen expression might be a clue to COVID-19 severity.

Influence of Preoperative Endoscopic Retrograde Cholangiopancreatography (ERCP) on Bacterial Colonization of Biliary Tract in Patients Surgically Treated for Obstructive Jaundice.

INTRODUCTION: Cancelling elective procedures on the day of surgery presents a constant problem in all higher-level medical facilities, and the research of causes, consequences and possible solutions is the duty of every facility in order to enhance the quality of healthcare services. METHODS: This prospective study included all patients that were scheduled for surgery from March 2016 to November 2018 in the operating rooms at our Department of Surgery, including both performed and cancelled cases. Cases by different surgical departments (general surgery, gynecology, orthopedics, urology, plastic surgery, ophthalmology and otorhinolaryngology) were all included. RESULTS: Out of 8201 planned elective procedures from March 2016 to November 2018 at the General Hospital "Abdulah Nakas", 7825 cases were performed and 376 cases (4.58%) were cancelled on the day of surgery. The most common reasons for cancelling a surgical procedure on the day of surgery were: lack of time to perform surgery, (33.51%), surgery cancelled due to medical/anesthetic reasons, (31.38%), surgical procedure cancelled by the surgeon on the day of surgery, (11.97%). CONCLUSION: This study has shown that the percentage of elective cases cancelled on the day of surgery at our institution stands at an acceptable 4.58%. The most common reasons for case cancellation on the day of surgery were identified. The majority of reasons for cancellation were avoidable, which means that appropriate steps could contribute to lowering the percentage of cancelled elective cases and an improved quality of healthcare services.