BACKGROUND: Acral actinic keratosis (AK) lesions are considered difficult to treat, and published data for photodynamic therapy (PDT) on these lesions is limited. Thus, we evaluated sustained efficacy, safety, and satisfaction after PDT for AK on the hands.
METHODS: We analysed subgroup data for treatment on the hands from a randomised, double-blind, intra-individual phase III study. All participants previously underwent up to two field-directed red light PDTs with 10% 5-aminolevulinic acid nanoemulsion gel (BF-200 ALA). Assessments included pain during PDT, clearance and recurrence rates, and satisfaction.
RESULTS: 24 participants treated on the hands were included; 21 participants were analysed. Complete clearance rates with BF-200 ALA were 90.9% (lesion-based) and 76.2% (per participant\'s side), both markedly higher than with vehicle. The lesion recurrence rate with BF-200 ALA was 29.0%. Adverse events reflected the mode of action. Mean pain intensities were 4.8 ± 3.8 (BF-200 ALA) and 0.8 ± 2.1 (vehicle) on an 11-point numeric rating scale. Most participants (81.0%) rated their satisfaction with BF-200 ALA as very good or good.
CONCLUSIONS: This subgroup analysis indicates that PDT with BF-200 ALA provides a suitable treatment for AK lesions on the hands.

This study aimed to evaluate the ability of photodynamic therapy, based on the use of a gel containing 5% delta aminolaevulinic acid (ALAD) for 45\' followed by irradiation with 630 nm LED (PDT) for 7\', to eradicate Candida albicans strains without damaging the gingiva. C. albicans oral strains and gingival fibroblasts (hGFs) were used to achieve these goals. The potential antifungal effects on a clinical resistant C. albicans S5 strain were evaluated in terms of biofilm biomass, colony forming units (CFU/mL) count, cell viability by live/dead analysis, and fluidity membrane changes. Concerning the hGFs, viability assays, morphological analysis (optical, scanning electronic (SEM), and confocal laser scanning (CLSM) microscopes), and assays for reactive oxygen species (ROS) and collagen production were performed. ALAD-mediated aPDT (ALAD-aPDT) treatment showed significant anti-biofilm activity against C. albicans S5, as confirmed by a reduction in both the biofilm biomass and CFUs/mL. The cell viability was strongly affected by the treatment, while on the contrary, the fluidity of the membrane remained unchanged. The results for the hGFs showed an absence of cytotoxicity and no morphological differences in cells subjected to ALAD-aPDT expected for CLSM results that exhibited an increase in the thickening of actin filaments. ROS production was augmented only at 0 h and 3 h, while the collagen appeared enhanced 7 days after the treatment.

Glioblastoma (GBM) is the most common adult brain cancer. Despite extensive treatment protocols comprised of maximal surgical resection and adjuvant chemo-radiation, all glioblastomas recur and are eventually fatal. Emerging as a novel investigation for GBM treatment, photodynamic therapy (PDT) is a light-based modality that offers spatially and temporally specific delivery of anti-cancer therapy with limited systemic toxicity, making it an attractive option to target GBM cells remaining beyond the margins of surgical resection. Prior PDT approaches in GBM have been predominantly based on 5-aminolevulinic acid (5-ALA), a systemically administered drug that is metabolized only in cancer cells, prompting the release of reactive oxygen species (ROS), inducing tumor cell death via apoptosis. Hence, this review sets out to provide an overview of current PDT strategies, specifically addressing both the potential and shortcomings of 5-ALA as the most implemented photosensitizer. Subsequently, the challenges that impede the clinical translation of PDT are thoroughly analyzed, considering relevant gaps in the current PDT literature, such as variable uptake of 5-ALA by tumor cells, insufficient tissue penetrance of visible light, and poor oxygen recovery in 5-ALA-based PDT. Finally, novel investigations with the potential to improve the clinical applicability of PDT are highlighted, including longitudinal PDT delivery, photoimmunotherapy, nanoparticle-linked photosensitizers, and near-infrared radiation. The review concludes with commentary on clinical trials currently furthering the field of PDT for GBM. Ultimately, through addressing barriers to clinical translation of PDT and proposing solutions, this review provides a path for optimizing PDT as a paradigm-shifting treatment for GBM.

BACKGROUND: Antimicrobial photodynamic therapy (aPDT) using aminolaevulinic acid (ALA) is a promising alternative to antibiotic therapy. ALA administration induces protoporphyrin IX (PpIX) accumulation in bacteria, and light excitation of the accumulated PpIX generates singlet oxygen to bacterial toxicity. Several factors, including drug administration and light irradiation conditions, contribute to the antibiotic effect. Such multiple parameters should be determined moderately for effective aPDT in clinical practice.
METHODS: A mathematical model to predict bacterial dynamics in ALA-aPDT following clinical conditions was constructed. Applying a pharmacokineticspharmacodynamics (PK-PD) approach, which is widely used in antimicrobial drug evaluation, viable bacteria count by defining the bactericidal rate as the concentration of singlet oxygen produced when PpIX in bacteria is irradiated by light.
RESULTS: The in vitro experimental results of ALA-aPDT for Pseudomonas aeruginosa demonstrated the PK-PD model validity. The killing rate has an upper limit, and the lower power density for a long irradiation time can suppress the viable bacteria number when the light dosages are the same.
CONCLUSIONS: This study proposed a model of bacterial viability change in ALA-aPDT based on the PK-PD model and confirmed, by in vitro experiments using PA, that the variation of bacterial viability with light-sensitive substance concentration and light irradiation power densities could be expressed. Further validation of the PK-PD model with other gram negative and gram positive strains will be needed.

Acute hepatic porphyrias (AHPs) are a family of four rare genetic diseases resulting from a deficiency in one of the enzymes involved in heme biosynthesis. AHP patients can experience potentially life-threatening acute attacks, characterized by severe abdominal pain, along with other signs and symptoms including nausea, mental confusion, hyponatraemia, hypertension, tachycardia and muscle weakness. Some patients also experience chronic manifestations and long-term complications, such as chronic pain syndrome, neuropathy and porphyria-associated kidney disease. Most symptomatic patients have only a few attacks in their lifetime; nevertheless, some experience frequent attacks that result in ongoing symptoms and a significant negative impact on their quality of life (QoL). Initial diagnosis of AHP can be made with a test for urinary porphobilinogen, [Formula: see text]-aminolaevulinic acid and porphyrins using a single random (spot) sample. However, diagnosis is frequently missed or delayed, often for years, because the clinical symptoms of AHP are non-specific and mimic other more common disorders. Delayed diagnosis is of concern as some commonly used medications can trigger or exacerbate acute attacks, and untreated attacks can become severe, potentially leading to permanent neurological damage or fatality. Other attack triggers include hormonal fluctuations in women, stress, alcohol and low-calorie diets, which should be avoided in patients where possible. For the management of attacks, intravenous hemin is approved, whereas new therapeutic approaches are currently being investigated as a baseline therapy for prevention of attacks and improvement of QoL. Among these, a novel siRNA-based agent, givosiran, has shown very promising results in a recently concluded Phase III trial and has been approved for the management of AHPs. Here, we propose a challenging case study-with a very unusual pediatric onset of variegate porphyria-as a starting point to summarize the main clinical aspects (namely, clinical manifestations, diagnostic challenges, and therapeutic management) of AHPs, with a focus on the latest therapeutic innovations.

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Locally advanced basal cell carcinoma (laBCC) is an uncommon cutaneous malignant tumor characterized by direct spread and extensive tissue destruction. The optimal therapy for laBCC remains a challenge, especially for elderly patients. Photodynamic therapy (PDT) has its advantage of better tumor selectivity, providing focal treatment for various non-melanoma carcinomas. We report that a new combination treatment of HiPorfin-photodynamic therapy (HiPorfin-PDT) and modified topical 5-aminolevulinic acid-photodynamic therapy (ALA-PDT), named bimodal PDT was successful to treat a 91-year-old patient with laBCC. As for side effects, hypertrophic scar and pain were observed. The symptoms were relieved after intralesional corticosteroid, 980 nm laser and 595 nm pulsed dye laser treatment in 3 months.

Dissecting cellulitis of the scalp (DCS) is difficult to be treated and 5-aminolaevulinic acid photodynamic therapy (ALA-PDT) is considered to be a potential treatment for inflammatory skin diseases.
To analyze the efficacy and safety of ALA-PDT on DCS.
The treatment areas of DCS patients were incubated with freshly prepared 10% ALA for 3 hours. The 633 ± 10 nm light with the intensity of 80-100 mw/cm2 was used as the irradiation source of ALA-PDT, and the irradiation time was 20-30 minutes. Three sessions were applied at an interval of 10-15 days. According to the reduction of lesions and the improvements of patients\' symptoms after each session, the objective assessment of therapeutic effect was divided into four grades. The adverse effects were recorded.
Seven male DCS patients finished the treatments and assessments. One month after three sessions of treatment, one patient recovered, three patients received significant improvement, and one patients received medium improvement. At the 3-month follow-up, two patients recovered, four patients received significant improvement, and one patients received medium improvement. The patients tolerated well to the therapy without any severe adverse effects.
10% ALA-PDT is effective and safe on male DCS patients. As a localized and less invasive treatment, it provides a preferable choice for DCS patients. Lasers Surg. Med. © 2018 Wiley Periodicals, Inc.

BACKGROUND: Sunlight can activate photodynamic therapy (PDT), and this is a proven strategy to reduce pain caused byconventional PDT treatment, but assessment of this and other alternative low dose rate light sources, and their efficacy, has not been studied in an objective, controlled pre-clinical setting. This study used three objective assays to assess the efficacy of different PDT treatment regimens, using PpIX fluorescence as a photophysical measure, STAT3 cross-linking as a photochemical measure, and keratinocyte damage as a photobiological measure.
METHODS: Nude mouse skin was used along with in vivo measures of photosensitizer fluorescence, keratinocyte nucleus damage from pathology, and STAT3 cross-linking from Western blot analysis. Light sources compared included a low fluence rate red LED panel, compact fluorescent bulbs, halogen bulbs and direct sunlight, as compared to traditional PDT delivery with conventional and fractionated high fluence rate red LED light delivery.
RESULTS: Of the three biomarkers, two had strong correlation to the PpIX-weighted light dose, which is calculated as the product of the treatment light dose (J/cm2) and the normalized PpIX absorption spectra. Comparison of STAT3 cross-linking to PpIX-weighted light dose had an R=0.74, and comparison of keratinocyte nuclear damage R=0.70. There was little correlation to PpIX fluorescence. These assays indicate most of the low fluence rate treatment modalities were as effective as conventional PDT, while fractionated PDT showed the most damage.
CONCLUSIONS: Daylight or artificial light PDT provides an alternative schedule for delivery of drug-light treatment, and this pre-clinical assay demonstrated that in vivo assays of damage could be used to objectively predict a clinical outcome in this altered delivery process.

BACKGROUND: Actinic keratoses are often treated by photodynamic therapy. However, the main side effect of this treatment is pain during and shortly after illumination.
OBJECTIVE: To evaluate, in an intra-individual study, whether the pain response differ in treatment of actinic keratoses in scalp and forhead, using branded methyl aminolevulinate (MAL) and aminolaevulinic acid (ALA).
METHODS: Patients with mild to moderate actinic keratoses on forehead and scalp were treated with methyl aminolaevulinate (MAL)-PDT and aminolaevulinic acid (ALA)-PDT on two similar areas of forehead and scalp. The pain response were measured using visual analogue scale ranging from 0 to 10 during the illumination and 30min after the treatment.
RESULTS: Fourteen patients completed treatment to MAL and ALA-PDT. We found no significant difference in pain intensity between MAL and ALA-PDT, neither during the treatment (p-value=1) nor 30min after the treatment (p-value of 0.19).
CONCLUSIONS: This intra-individual study demonstrate no significant difference between the pain response during PDT using methyl aminolevulinate and aminolaevulinic acid.