Exosomes as therapeutic and drug delivery vehicle for neurodegenerative diseases.

Neurodegenerative disorders are complex, progressive, and life-threatening. They cause mortality and disability for millions of people worldwide. Appropriate treatment for neurodegenerative diseases (NDs) is still clinically lacking due to the presence of the blood-brain barrier (BBB). Developing an effective transport system that can cross the BBB and enhance the therapeutic effect of neuroprotective agents has been a major challenge for NDs. Exosomes are endogenous nano-sized vesicles that naturally carry biomolecular cargoes. Many studies have indicated that exosome content, particularly microRNAs (miRNAs), possess biological activities by targeting several signaling pathways involved in apoptosis, inflammation, autophagy, and oxidative stress. Exosome content can influence cellular function in healthy or pathological ways. Furthermore, since exosomes reflect the features of the parental cells, their cargoes offer opportunities for early diagnosis and therapeutic intervention of diseases. Exosomes have unique characteristics that make them ideal for delivering drugs directly to the brain. These characteristics include the ability to pass through the BBB, biocompatibility, stability, and innate targeting properties. This review emphasizes the role of exosomes in alleviating NDs and discusses the associated signaling pathways and molecular mechanisms. Furthermore, the unique biological features of exosomes, making them a promising natural transporter for delivering various medications to the brain to combat several NDs, are also discussed.

Beyond the Label: Real-World Side Effects Experienced With FDA-Approved Drugs for Non-Melanoma Skin Cancers.

With immunotherapy historically focused on cutaneous melanoma, there has been a new wave of systemic medications available for treating non-melanoma skin cancers including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and Merkel cell carcinoma (MCC). The immune checkpoint inhibitors approved by the FDA target programmed cell death protein 1 (PD-1) and the Hedgehog (Hh) signaling pathway. These medications have expanded treatment options; however, side effects are an important consideration. We used the FDA Adverse Events Reporting System (FAERS) to characterize the most prevalent, real-world side effects experienced by patients on these agents. Muscle spasms (23.45%), alopecia (16.06%), ageusia (12.02%), taste disorder (11.91%), and fatigue (11.67%) were the five most common side effects reported with medications used for BCC treatment. Logistic regression analysis showed males on vismodegib for BCC having greater odds of experiencing muscle spasms (aOR 1.33, P<0.001) and ageusia (aOR 1.34,  P<0.001) versus females, who were more likely to exhibit alopecia (aOR 1.82, P<0.001) and nausea (aOR 1.96, P<0.001). With SCC treatment, the 5 most reported adverse events were fatigue (5.58%), rash (3.59%), asthenia (3.59%), pruritus (3.19%), and pyrexia (2.79%). Patients taking cemiplimab-rwlc for BCC compared to SCC were more likely to experience disease progression (aOR 10.98, P=0.02). With medication labels providing an excessively daunting list of side effects, we characterize practical side effects seen in patients receiving systemic treatments for non-melanoma skin cancers.  J Drugs Dermatol. 2024;23(5):301-305. doi:10.36849/JDD.7968.

Assessing the readability and quality of online patient information for laser tattooremoval.

Just as tattoos continue to increase in popularity, many people with tattoos also seek removal, often due to career concerns. Prospective clients interested in laser tattoo removal may do research about the procedure online, as the internet increasingly becomes a resource to get preliminary health information. However, it is important that the online health information on the topic be of high quality and be accessible to all patients. We analyzed 77 websites from a Google search query using the terms "Laser tattoo removal patient Information" and "Laser tattoo removal patient Instructions" to assess this. The websites were evaluated for their readability using multiple validated indices and comprehensiveness. We found that websites had a broad readability range, from elementary to college, though most were above the recommended eighth-grade reading level. Less than half of the websites adequately discussed the increased risk of pigmentary complications in the skin of color clients or emphasized the importance of consulting with a board-certified dermatologist/plastic surgeon before the procedure. Over 90% of the websites noted that multiple laser treatments are likely needed for complete clearance of tattoos. The findings from our study underscore a significant gap in the accessibility and quality of online information for patients considering laser tattoo removal, particularly in addressing specific risks for patients with darker skin tones and emphasizing the need for consulting a board-certified physician before undergoing the procedure. It is important that online resources for laser tattoo removal be appropriately written to allow better decision-making, expectations, and future satisfaction for potential clients interested in the procedure.

Lasers in the management of alopecia: a review of established therapies and advances in treatment.

Alopecia, also known as hair loss, is a highly prevalent condition affecting millions of men and women in the United States and worldwide, making it one of the most common complaints by patients presenting to a dermatologist. The symptomology on the presentation of alopecia can be highly variable, ranging from diffuse thinning of hair, discrete and localized patches completely absent of hair, or noticing significant shedding when brushing and showering. Although alopecia does not have a direct negative health impact on patients, it is nonetheless a debilitating disease as it can profoundly impact an individual's self-image and psychosocial well-being. There are multiple treatment options available to patients with alopecia, and they are typically tailored to the patient's needs and preferences. The most common of these is the Food and Drug Administration-approved drugs for alopecia, minoxidil, and finasteride. However, both of these are known to be partially efficacious for all patients, so clinicians often use different modalities in conjunction with them, in particular laser-based therapies. This review article will provide a comprehensive assessment of lasers and other light therapies that may be used to manage the two most common types of alopecia: androgenetic alopecia and alopecia areata.

The Impact of Acculturation on Skin Cancer Risk and Protective Behaviors in Hispanic Populations.

The US Hispanic population faces rising skin cancer risks and poorer clinical outcomes, despite lower incidence rates. Acculturation, adopting elements of the dominant culture, may influence skin cancer attitudes and behaviors among Hispanics. We systematically reviewed PubMed articles from 2000 to 2023. Peer-reviewed English articles that assessed the relationship between acculturation and skin cancer in the Hispanic population were included. Andreeva et al. observed that lower acculturation levels correlated with increased use of shade and protective clothing (P < 0.05). More acculturated Latinos were more likely to use sunscreen, but this association weakened after adjusting for covariates (P > 0.48). Heckman et al. highlighted significant differences in skin cancer concern among Hispanic youth, with less acculturated individuals expressing greater worry (P < 0.05). Coups et al. found that higher acculturation was linked to less sun protective clothing usage and more frequent sunburns. Their subsequent online survey indicated that English-acculturated Hispanics engaged less in protective behaviors. Viola et al. reported that English-acculturated Hispanics perceived greater suntan benefits and had lower perceptions of skin cancer risk, severity, and concerns about photo-aging, along with higher melanoma risk factors, compared to Spanish-acculturated Hispanics. Acculturation influences skin cancer attitudes and behaviors in Hispanics. Tailored interventions based on acculturation levels are essential to reduce skin cancer risk. For example, educating English-acculturated Hispanics about skin cancer risks and prioritizing knowledge dissemination for Spanish-acculturated individuals may be effective approaches. These findings emphasize the need for targeted skin cancer prevention efforts to address disparities among US Hispanics.

Evaluation of risk in chronic cutaneous inflammatory conditions for malignant transformation.

Skin carcinomas are the most common form of cancer, and every year thousands of people die from skin cancer-related malignancies. Chronic inflammation is linked to the development and progression of cancer in multiple organ systems - about 20% of all human cancers are a result of chronic inflammation - skin included. While acute inflammation under normal circumstances is a mechanism for host defence and tissue regeneration following insult by trauma or infection by pathogens, over the long term it can drive oncogenic transformation of epithelial cells and promote cancer development, growth and metastasis. Therefore, inflammatory conditions may put individuals at a higher risk to developing skin malignancies. Many skin conditions are characterized by chronic inflammatory processes. These conditions may be particularly susceptible to malignant transformation and predispose patients to develop skin malignancies. As more pathophysiology of chronic inflammatory skin conditions is unveiled, we find that many of these conditions are characterized by immune dysregulation and signalling that result in chronic activation and upregulation of pro-inflammatory chemokines and cytokines, leading to downstream processes that further exacerbate inflammatory processes and cause abnormal cell growth and apoptosis. Here, we review the major chronic cutaneous inflammatory diseases that may have an increased risk of skin malignancies, including atopic dermatitis, psoriasis, discoid lupus erythematosus, lichen planus, hidradenitis suppurativa, prurigo nodularis, lichen sclerosus, systemic sclerosis and morphea, chronic leg ulcers, seborrheic keratoses and basal cell carcinoma. We evaluate the evidence for increased incidence and prevalence, the risk factors associated, the populations at heightened risk and the best management practices.

Comparing the efficacy and safety of laser treatments in tattoo removal: A systematic review.

BACKGROUND: Although lasers have been the criterion standard for tattoo removal, selecting the best modality can be challenging because of the varying efficacies and adverse effects. OBJECTIVE: To evaluate all lasers used to remove tattoos and assess their efficacies and adverse effects. METHODS: Our systematic review searched PubMed, MEDLINE, Embase, Scopus, CINAHL, Cochrane Central Register of Trials, and ClinicalTrials.gov for all laser treatments. The outcomes measured included laser parameters, treatment methods, patient and tattoo characteristics, clearance rate, and adverse effect rate. The quality of the included articles was appraised by using specific assessment tools and given a high, moderate, or low risk of bias. RESULTS: Our search led to 3037 studies, with 36 being included in the systematic review (7 randomized controlled trials, 2 nonrandomized controlled trials, and 27 case series). Although quality-switched neodymium-doped yttrium-aluminum-garnet lasers are safe and effective, picosecond lasers have shown superiority with blue, green, and yellow tattoo pigments. Both are safe and effective for black tattoos. LIMITATIONS: Variability among studies. CONCLUSIONS: Picosecond lasers show superiority when treating blue, green, and yellow tattoos. The R20 and R0 novel techniques can effectively reduce treatment time. Further randomized controlled trials are required to make a more definitive recommendation.

Squamous cell carcinoma: 2021 updated review of treatment.

Squamous cell carcinoma is the second most common cutaneous malignancy, requiring early diagnosis to prevent metastasis. Updated guidelines in the definition of clinical features, diagnostic modalities, grading, staging, surgical, and nonsurgical treatment methods are necessary. Diagnostic methods from biopsy, dermoscopy, and reflectance confocal microscopy have improved to include high-frequency ultrasonography, optical coherence tomography, and computed tomography. Non-surgical treatment methods include topical therapy, cryosurgery, photodynamic therapy, and radiation. Surgical treatment methods include surgical excision with margins and Mohs surgery. Clinical trials encourage further research to address the knowledge base of genetic variations and lymph node metastasis.

Acne treatment review and future perspectives.

Acne affects approximately 9% of people worldwide and is the most common skin condition in the USA. There are abundant topical and oral treatment options available for patients with acne. First-line agents include topical retinoids, azelaic acid, benzoyl peroxide, and combinations of these agents. For recalcitrant or more severe acne, oral medications, including oral antibiotics, isotretinoin, or hormonal therapy, may be considered. This review will also discuss the many advances being made in the treatment of acne vulgaris, from the development of microencapsulated medications to targeted treatments.

Basal cell carcinoma: An updated review of pathogenesis and treatment options.

Basal cell carcinoma (BCC) remains the most common malignancy worldwide. BCC pathogenesis is a result of the interplay between one's environment, genetics, and phenotypic factors. BCC has a low mortality but given its increasing incidence and potential to cause local destruction thus resulting in significant morbidity, it is vital for dermatologists to remain up to date with recent updates in this malignancy's pathogenesis and treatment. This article provides a comprehensive review of the pathogenesis of BCC as well as the current treatments available and clinical trials underway. We also touch upon the updated National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology in respect to BCC's recommended treatment modalities.

Merkel cell carcinoma: An updated review of pathogenesis, diagnosis, and treatment options.

Merkel cell carcinoma is a rare neuroendocrine carcinoma that typically appears in sun-exposed areas of the elderly. It has a poor prognosis and with its incidence projected to increase, it is vital for dermatologists to remain up to date with recent updates in this malignancy's pathogenesis and treatment. In the past few decades Merkel cell carcinoma's pathogenesis, more specifically its relation to the Merkel cell polyomavirus, has sparked further interest in the study of this carcinoma. Most cases are attributed to malignant transformation secondary to the Merkel cell polyomavirus, with a minority derived from DNA damage resulting from ultraviolet radiation. Investigators have also determined that there are immunologic influences in the development and prognosis of Merkel cell carcinoma, as individuals with HIV, solid organ transplants, and lymphoproliferative malignancies are at a greater risk of developing this carcinoma. In addition, this immunologic link carries treatment value, as immunologic therapies are currently being investigated. This article provides a comprehensive review of the epidemiology and pathogenesis of Merkel cell carcinoma as well as the current treatments available and clinical trials underway. We also touch upon the updated National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology in respect to its diagnosis and recommended treatment modalities.

Review of the current antibiotic guidelines used in dermatologic surgery.

Antibiotics have been used as a prophylaxis for dermatologic procedures. We will review the various procedures that specific antibiotics with dosages are used for, depending on the procedure, diagnosis, and circumstance of the patient. We will examine the current and updated guidelines used in dermatologic surgery and the overlapping guidelines across other fields. Physicians must consider the side effects of antibiotics and the resistance that may occur as a result before using the class or level of prophylaxis. Initial evaluation for alcohol, chlorhexidine, or iodine should be measured as well. Updated guidelines aim to address the contraindications of antibiotics, yet further research is needed to avoid antibiotic resistance and to explore alternative methods of antibiotic application, such as intranasal and intravenous.

Perioperative Anxiety Associated With Mohs Micrographic Surgery: A Survey-Based Study.

BACKGROUND: Mohs micrographic surgery (MMS)-associated anxiety is an important issue that remains poorly discussed. Identifying risk factors for MMS-associated anxiety will better equip physicians to manage patients' preoperative anxiety and result in improved patient satisfaction and outcomes. OBJECTIVE: This study aims in identification of risk factors that may play a role in MMS-associated anxiety among patients with nonmelanoma skin cancer. METHODS: A cross-sectional case series was conducted among MMS patients collect information on patient demographics and surgical locations and to measure perioperative anxiety and quality of life (QoL). In addition, adjusted linear and logistic regression analyses were performed to identify potential risk factors that predict MMS-associated anxiety. RESULTS: Significant increases in perioperative anxiety were associated with the eyelid area compared with the noneyelid facial area and nonfacial area ( p ≤ .05). Patients with graduate degrees exhibited less anxiety compared with ones who received less education ( p ≤ .05). Higher perioperative anxiety was associated with a greater impact on QoL ( p ≤ .05). CONCLUSION: This study identified that surgical location and the patient's educational level are 2 critical predicting factors for perioperative anxiety. Furthermore, perioperative anxiety could negatively affect a patient's quality of life and warrants further investigation into effective management.

Laser tattoo removal: laser principles and an updated guide for clinicians.

Tattoos have become ingrained in our society and have served varied purposes throughout human civilization. So long as tattoos have existed, there has been demand for their removal. Lasers are currently the modality of choice in the removal of tattoos, as they are more efficacious than previously used methods. The most common lasers are the 532 nm and 1064 nm neodymium-doped yttrium aluminum garnet lasers, the quality-switched 694 nm Ruby laser, and the quality-switched 755 nm alexandrite laser. However, picosecond lasers are rapidly gaining favor in tattoo removal. An in-depth understanding of laser principles and how they can be applied in the setting of tattoo removal is key. Also, a greater understanding of the origin of and colors within a tattoo, the presence of tattoo layering, and a patient's Fitzpatrick skin type increase the odds of satisfactory results. This review provides dermatologists with a comprehensive summary on laser fundamentals, an overview on treatment principles, and recent developments in the field of laser tattoo removal.

The clinical utility of teledermoscopy in the era of telemedicine.

Teledermoscopy is a novel diagnostic tool for the prevention, diagnosis, and treatment of skin disease when direct visualization of lesions is difficult. It is an economically viable option that can complement telehealth visits and that providers can utilize to identify melanocytic lesions and optimize care with diagnostic accuracy comparable to face-to-face (FTF) diagnosis. Teledermoscopy is invaluable in monitoring chronic conditions that require frequent follow-up and treatment optimization. Inclusion of clinical and dermoscopic images has been shown to improve the diagnostic accuracy of teledermatology services, thereby reducing healthcare costs. Teledermoscopy is also non-discriminatory, as diagnostic accuracy is similar in lighter and darker skin types. It has been shown to improve patient access to specialty services and reduce the number of "no-shows" at FTF clinics and length of surgery waiting times. Mobile teledermoscopy is user-friendly, feasible, and economically viable, as inexpensive mobile dermatoscopes have emerged on the market to reduce consumer out-of-pocket costs. Research is limited on teledermoscopy's utility in diagnosing pre-cancerous and cancerous skin lesions in adults, particularly complex pigmented lesions. Further research is recommended to investigate the role of dermoscopic expertise and artificial intelligence on the evaluation of teledermoscopic images.

Pruritus in Keloid Scars: Mechanisms and Treatments.

Keloids are scars that extend beyond the margins of an insulting cutaneous injury. Keloids are often thought to be primarily a cosmetic issue, as they are typically quite raised and pigmented. However, these scars also present with functional symptoms of pruritus and pain that significantly impact quality of life. The symptom of pruritus is frequently overlooked by dermatologists, and treatments are often primarily focused on the gross appearance of the scar. This review describes the prevalence and importance of pruritus in keloids. In addition, the putative mechanisms underlying the development of keloid pruritus, which include neuronal and immunological mechanisms, are discussed. Furthermore, this review describes keloid treatments that have been shown to reduce pruritus, treatments that specifically target the itch, and emerging therapies.

Comparing the efficacy and safety of Q-switched and picosecond lasers in the treatment of nevus of Ota: a systematic review and meta-analysis.

Nevus of Ota is cosmetically burdensome and often prompts patients to seek treatment. Lasers are commonly used in removing these lesions; however, no systemic analysis has been conducted to support a gold standard laser. To conduct a meta-analysis of the efficacy and safety of Q-switched Nd:YAG lasers (QSNL), Q-switched ruby lasers (QSRL), Q-switched alexandrite lasers (QSAL), and picosecond alexandrite lasers (PSAL) in removing nevus of Ota. Inclusion criteria were nevus of Ota patients treated with QSNL, QSRL, QSAL, or PSAL and documentation of percent clearance and the rate of at least one adverse event. Articles in English, Chinese, or Japanese were included. The prespecified outcome measures were efficacy (percent clearance) and safety (rates of hyperpigmentation, hypopigmentation, scarring, and recurrence). The review included 57 studies and 13,417 patients. The pooled success rate was 64% for QSNL (95% CI 52-76%), 54% for QSRL (95% CI 39-69%), 58% for QSAL (95% CI 44-72%), and 100% for PSAL (95% CI 98-102%). The pooled adverse event rate was 5% for QSNL (95% CI 4-6%), 14% for QSRL (95% CI 9-19%), 9% for QSAL (95% CI 6-12%), and 44% (95% CI 31-57%) for PSAL. QSNL has the most evidence for effectively and safely treating nevus of Ota. PSAL potentially has a superior efficacy; however, further studies are needed to elucidate its side effect profile when treating nevus of Ota.

Blinded, Randomized, Controlled Trial Evaluating the Effects of Light-Emitting Diode Photomodulation on Lower Extremity Wounds Left to Heal by Secondary Intention.

BACKGROUND: Light-emitting diode (LED) has been used for wound healing because of its stimulatory effects on fibroblast proliferation, matrix synthesis, angiogenesis, and downmodulation of inflammatory reactions. OBJECTIVE: The aim of the authors' study was to investigate the effects of red LED (wavelength 633 nm) photomodulation on lower extremity surgical defects left to heal by secondary intention. MATERIALS AND METHODS: Fourteen subjects with surgical defects of the lower leg were irradiated with a 633 ± 3-nm light source for 20 minutes (105 mW/cm, 126 J/cm) at 4 weekly sessions. RESULTS: The number of days required for wounds to heal was greater in the treatment group (63.2 ± 12.2 days) than in the control group (48.67 ± 11.1 days), although this difference was not statistically significant (p = .07). The percentage of the original wound remaining was not statistically different between treatment and control groups between Weeks 1 and 2 (p = .71) and Weeks 3 and 4 (p = .56). It was significant between Weeks 2 and 3 (p = .01). CONCLUSION: This study revealed that red LED photomodulation at a wavelength of 633 nm did not result in clinical improvement in wound healing of surgical defects on the lower extremities.

Teledermatology: Improving Access or Widening Healthcare Disparities?

Teledermatology, the form of telemedicine directed toward dermatology patients, is one of the earliest technological innovations that advanced remote medical care. Developed in 1995, teledermatology was established with the mission of increasing healthcare access among patients in rural geographic locations who had limited access to specialist care.1.

Effectiveness of Pediatric Teledermatology.

Initial studies of teledermatology in pediatric populations indicated that many of the problems experienced in adult virtual visits were even more apparent when treating children. Specifically, it was noted that the difficulty in obtaining medical history and participation of the pediatric patients provided additional challenges in evaluation.1 Direct-to-consumer models have highlighted many of these challenges as well as a general lack of continuity of care previously seen in pediatric teledermatology. Addressing these challenges may be accomplished by further involving parents in the teledermatology workflow.