Analysis and evaluation of the operational characteristics of a new photodynamic therapy device.

One of the key aspects of photodynamic therapy is the light source that is used to irradiate the lesion to be treated. The devices used must ensure that their emission spectrum matches the absorption spectrum of the photosensitizer, so that treatment radiation is delivered only on the target area, without irradiating healthy tissue at superficial or deep levels. Irradiance values must be adequate in order to avoid thermal damage, exceed the oxygen replenishment rate and avoid long treatment times. Furthermore, the device should be user-friendly, inexpensive, and able to be adapted to different photosensitizers. We have developed an easy-to-use and highly customizable device based on LED technology. Its innovative geometric design allows radiation to be delivered to a small treatment surface, since the LEDs are arranged in three arms, the configuration of which directs their radiation on the treatment point. Different high-power color LEDs are disposed on the arms, and can be independently selected based on the most effective wavelengths for exciting the different photodynamic therapy photosensitizers. We have tested the prototype in 5 different patients (1 actinic keratose, 1 actinic cheilitis, 1 superficial basal cell carcinoma and 2 Bowen's disease) and after 1-2 sessions of total cumulative dose of 25-50 J / cm2, 100% clearance of lesions were obtained. Our device can be used by any professional in the field, whether for medical or research purposes. It facilitates the development of treatment protocols and trials with different photosensitizers.

Recent Advances on Immunosuppressive Drugs and Remyelination Enhancers for the Treatment of Multiple Sclerosis.

Mammalian nervous systems depend crucially on myelin sheaths covering the axons. In the central nervous system, myelin sheaths consist of lipid structures that are generated from the membrane of oligodendrocytes (OL). These sheaths allow fast nerve transmission, protect axons and provide them metabolic support. In response to specific traumas or pathologies, these lipid structures can be destabilized and generate demyelinating lesions. Multiple sclerosis (MS) is an example of a demyelinating disease in which the myelin sheaths surrounding the nerve fibers of the brain and spinal cord are damaged. MS is the leading cause of neurological disability in young adults in many countries, and its incidence has been increasing in recent decades. Related to its etiology, it is known that MS is an autoimmune and inflammatory CNS disease. However, there are no effective treatments for this disease and the immunomodulatory therapies that currently exist have proven limited success since they only delay the progress of the disease. Nowadays, one of the main goals in MS research is to find treatments which allow the recovery of neurological disabilities due to demyelination. To this end, different approaches, such as modulating intracellular signaling or regulating the lipid metabolism of OLs, are being considered. Here, in addition to immunosuppressive or immunomodulatory drugs that reduce the immune response against myelin sheaths, we review a diverse group of drugs that promotes endogenous remyelination in MS patients and their use may be interesting as potential therapeutic agents in MS disease. To this end, we compile specific treatments against MS that are currently in the market with remyelination strategies that have entered into human clinical trials for future reparative MS therapies. The method used in this study is a systematic literature review on PubMed, Web of Science and Science Direct databases up to May 31, 2020. To narrow down the search results in databases, more specific keywords, such as "myelin sheath", "remyelination", "demyelination", "oligodendrocyte" and "lipid synthesis" were used to focus the search. We preferred papers published after January 2015, but did not exclude earlier seminal papers.

Effect of Nail Thickness on Visible Radiation Transmittance: Implications for New Photodynamic Therapy Technologies in Onychomycosis.

Photodynamic therapy is taking importance as a nonintrusive treatment for nail onychomycosis. Knowledge of true transmittance values across nails could lead to qualitative and quantitative improvements in light-based treatments. We have characterized the spectral transmittance of healthy and fungally infected human fingernails and toenails according to nail thickness, and we propose a surface transmittance model for the small-scale optimization of light-based treatments. Transmittance of fingernails and toenails was analyzed by means of spectroradiometric measurements under solar-simulated visible light radiation (400 nm to 750 nm). The nail thickness was measured by means of microscope measurement. Transmittance was highest at longer wavelengths and decreased gradually as the wavelengths became shorter but with a significant nail transmittance of around 20% in the blue region of the spectrum. In the case of nails affected by onychomycosis, transmittance fell to under 10% because of the thickness of the nails, with no changes in spectral characteristics of transmitted light. Nail thickness is the main variable controlling exponentially light transmission in the visible spectrum and not only red radiation is effective for nail onychomycosis PDT. Blue light, the spectral band more effective for PPIX absorption is also effectively transmitted.

Fatty Acids and Antioxidants in Multiple Sclerosis: Therapeutic Role of GEMSP.

Multiple sclerosis is a high-frequency neurological disorder in young adults. Although there are some genetic and environmental factors that have been related to the onset of the disease, these are still not completely understood and nowadays multiple sclerosis can neither be prevented, nor its symptom effectively treated due to disease heterogeneity. For this reason, the search of prognostic factors and new therapeutic compounds for MS has long aroused among clinicians and researchers. Among these therapeutic compounds, GEMSP, which consists of a mixture of functional constituents as fatty acids, antioxidants, free radical scavengers and amino acids linked individually to poly-L-Lysine (PL), is emerging as a promising drug for MS treatment. Pre-clinical studies using GEMSP have demonstrated that this drug strongly inhibits brain leukocyte infiltration and completely abolishes experimental autoimmune encephalomyelitis. In addition, in an open clinical trial in humans treated with GEMSP, in 72% of the cases, a positive evolution of the state of the MS patients treated with GMSP was observed. In this review a biochemical characterization of main constituents of GEMSP, which include fatty acids as oleic acid, linoleic acid or azelaic acid and the antioxidants alpha-tocopherol or ascorbic acid, will be provided in order to understand their proved therapeutic effects in MS.

Low-level light-assisted photodynamic therapy using a wearable cap-like device for the treatment of actinic keratosis of the scalp.

BACKGROUND: Daylight photodynamic therapy (dlPDT) is a painless and increasingly cost-effective treatment for actinic keratosis (AK). New protocols avoid incubation, minimizing pain and adverse events. However, it is time-consuming and dependent on specific weather conditions. In patients with AK of the scalp, we evaluated the efficacy of indoor photodynamic therapy (PDT) using a wearable low-level light therapy (LLLT) device, without pre-incubation with a photosensitizing agent. METHODS: In this pilot study, 27 patients with thin and moderately thick AK (Olsen Grades I-II) underwent a single 15-minute session of LLLT using a wearable cap-like device immediately after application of methyl-aminolevulinate (MAL) cream, with no prior preparation of the affected area. Treatment efficacy was quantified by measuring the reduction in AK lesion number and the AK quality of life (AKQoL) score. All AK lesions were mapped at baseline for follow-up 2 months later. Paired pre/post scalp biopsies from 5 patients were analysed using histological and immunohistochemical techniques (p53, p27, cyclin D1, p63, and Ki67 expression). Data were analysed using the Wilcoxon signed-rank test. RESULTS: In all patients we observed a global reduction in the number of AK lesions (71%; p < 0.0001) and AKQoL score (from 5.6 to 4.4; p = 0.034) 2 months after treatment. Histology and immunohistochemistry of skin biopsies from 5 patients also revealed marked improvements after LLLT. No patients reported any pain during treatment. CONCLUSION: PDT using LLLT is a rapid, painless, and efficacious modality for the treatment of AK.

Hormonal and Gynecological Risk Factors in Frontal Fibrosing Alopecia: A Case-Control Study.

INTRODUCTION: Frontal fibrosing alopecia (FFA) is a condition that likely involves an interplay of autoimmune, hormonal, and environmental factors in its pathogenesis. There is a lack of comparative studies demonstrating the presence of hormonal background differences in FFA patients compared to the general population. MATERIALS AND METHODS: A single-center case-control study was designed, including 104 female FFA patients and 208 controls. Patients and controls were interviewed, and extensive data regarding their gynecological and hormonal background were recorded. RESULTS: One hundred four cases and 208 age-matched controls were included in the study. A significant difference of 2 years in the age of menopause was detected with a consistent mean increase in fertile life for the control group of 1.7 years. After the multivariate analysis, we found previous intake of tamoxifen to be a risk factor for the development of FFA (OR 14.89). The only protective factor identified was the previous use of an intrauterine device (IUD) (OR 0.22). CONCLUSIONS: An earlier menopause and tamoxifen intake might promote or maintain FFA, while the use of an IUD might protect from developing FFA. Our results support the previously proposed hypothesis of an underlying hormonal mechanism in the etiopathogenesis of FFA and point out low-estrogen environments as an ideal condition for FFA development.

Treatment of flat and elevated pigmented disorders with a 755-nm alexandrite picosecond laser: clinical and histological evaluation.

The novel picosecond lasers, initially developed for faster tattoo removal, have also shown great efficacy in endogenous pigmentary disorders. To describe the efficacy and safety profile of an alexandrite (755-nm) picosecond laser in a wide range of pigmented flat and elevated cutaneous lesions. A retrospective study was performed in which we collected all the clinical images of patients treated with the 755-nm alexandrite picosecond laser for 12 months (November 2016-November 2017). Clinical features were obtained from their medical charts. Patients treated for tattoo removal were excluded. All the images were analyzed by three blind physicians attending to a visual analogue scale (VAS) from 0 to 5 (0, no change; 1, 1-24% clearance; 2, 25-49% clearance; 3, 50-74% clearance; 4, 75-99% clearance; 5, complete clearance). Patient satisfaction was obtained from a subjective survey including four items: very satisfied, satisfied, non-satisfied, and totally dissatisfied. Thirty-seven patients were included (12 males; 25 females). The mean age of the study was 42.35 years. Twenty-five patients (68%) were treated for different pigmented flat disorders such as solar and mucosal lentigines (5), stasis dermatitis (4), or nevus of Ota (4), among other diagnoses. Twelve patients (32%) were treated for epidermal elevated lesions such as warts (5), epidermal nevi (2), and seborrheic keratosis (3), among other elevated lesions. Mean number of laser treatment was 3.02 sessions while mean follow-up after last laser treatment was 4.02 months. Mean VAS score of the three observers was 3.44 (61% of clearance) for pigmentary flat disorders and 3.60 (67%) for elevated lesions. Adverse effects reported were mild blistering in the first 2-5 days following laser treatment in some of the patients. Overall satisfaction among the patients included was high. The novel 755-nm picosecond alexandrite laser is effective not only for the resolution of pigmented flat lesions of different nature but also for the treatment of the more difficult elevated pigmented lesions.

Impact of Folliculitis Decalvans on Quality of Life and Subjective Perception of Disease.

Folliculitis decalvans (FD) is a primary neutrophilic scarring alopecia characterized by perifollicular papules, crusts, and pustules frequently located on the vertex. FD may affect young men and women. Since it may lead to hair loss, it can have a negative impact on patients' quality of life. Nevertheless, studies have focused on clinical, prognostic, and therapeutic aspects without considering the psychological impact of FD. In our study, we found that FD patients experienced a considerable impact on their quality of life. Interestingly, almost half of the patients considered that their alopecia was related to a poor medical care in their past. To our knowledge, this is the first description of the impact of FD on patients' quality of life, and it highlights the importance of psychological support for these patients.

Development and validation of the Frontal Fibrosing Alopecia Severity Score.

BACKGROUND: Frontal fibrosing alopecia (FFA) is a scarring alopecia characterized by recession of the frontotemporal hairline and loss of the eyebrows. OBJECTIVE: To design and validate a scoring system to assess the severity of FFA. METHODS: The Frontal Fibrosing Alopecia Severity Score (FFASS) was developed; criterion validity was assessed by the Investigator's Global Assessment, and construct validity was evaluated by the convergence of other measures of severity (the Patient's Global Assessment], the rest of the clinical features, the Lichen Planopilaris Activity Index, and quality of life measures (Dermatology Life Quality Index and Hospital Anxiety Depression Scale). Intraobserver and interobserver reliability were determined. RESULTS: In total, 103 female patients were included. The FFASS showed significant correlation to the Patient's Global Assessment, occipital involvement, and the Lichen Planopilaris Activity Index. Intraobserver reliability was completed for 31 subjects and showed good correlation (intraclass correlation coefficient, 0.86; 95% confidence interval, 0.7-0.95; P < .001). Interobserver reliability showed excellent correlation (intraclass correlation coefficient, 0.97; 95% confidence interval, 0.95-0.99; P < .001). LIMITATIONS: The study was performed at a single institution, and only female patients were assessed. CONCLUSIONS: The FFASS is a statistically validated scale and a reliable measure of FFA severity, and it can be used in clinical practice and future research studies as an assessment tool.