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IMPORTANCE Skin pretreatment is recommended for adequate penetration of topical photosensitizing agents and subsequent protoporphyrin IX (PPIX) accumulation in photodynamic therapy (PDT).OBJECTIVE To compare the relative potential of different physical pretreatments to enhance PPIX fluorescence in normal skin. DESIGN, SETTING, AND PARTICIPANTSThis intraindividual, randomized clinical trial was performed from November 28 to December 20, 2014, at Bispebjerg Hospital, Copenhagen, Denmark, among 12 healthy volunteers 18 years or older. Analysis was based on intention to treat. All participants completed the study protocol.INTERVENTIONS Participants were each exposed to standardized skin preparation with curettage, microdermabrasion with abrasive pads, microneedling with dermarollers, ablative fractional laser (AFXL), non-AFXL, and no pretreatment, followed by 3 hours of methyl aminolevulinate hydrochloride incubation and subsequent red light illumination. MAIN OUTCOMES AND MEASURESThe primary outcome measure was methyl aminolevulinate-induced PPIX fluorescence accumulation. Secondary outcome measures were PPIX photobleaching and clinical local skin reactions, supported by noninvasive reflectance measurements of percentage of skin redness, transepidermal water loss, and participant-assessed pain.RESULTS Among the 12 healthy study participants (8 men; 4 women; mean [SD] age, 33 [15] years), histologic findings confirmed standardization of interventions with partial removal of the stratum corneum after curettage and microdermabrasion and similar vertical penetration depths for microneedling, AFXL, and non-AFXL (median, 125 μm). PPIX fluorescence reached highest intensities in skin pretreated with AFXL (median, 8661 arbitrary units [AU]) compared with microdermabrasion (median, 6731 AU), microneedling (median, 5609 AU), and curettage (median, 4765 AU) (P < .001), among which similar enhancement was shown. Comparatively lower fluorescence levels were demonstrated for skin pretreated with non-AFXL (median, 2898 AU), methyl aminolevulinate-treated controls (median, 2254 AU), and untreated controls (median, 239 AU) (P < .03). Increasing laser densities (2% vs 4% vs 6%) and the number of pretreatment passes (1, 2, and 3 passes) did not enhance PPIX fluorescence. Local skin reactions were most intensified in AFXL-pretreated skin and correlated with PPIX fluorescence and degree of PPIX photobleaching.CONCLUSIONS AND RELEVANCE Under standardized conditions, PPIX accumulation was most enhanced after AFXL pretreatment, followed by microdermabrasion, microneedling, and curettage. Increasing the number of pretreatment passes and laser densities did not further augment PPIX accumulation. These results may indicate relatively enhanced PDT response by AFXL pretreatment in diseased skin. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT02372370

The accuracy in the hypoglycemic range of nocturnal CGM data using Sof-Sensor is suboptimal in type 1 diabetes patients at high risk of severe hypoglycemia. To ensure clinical useful sensitivity in detection of nocturnal hypoglycemic episodes, an alarm threshold should not be lower than 4 mmol/L.

The time frame to maintain enhanced drug delivery sustained for several hours after AFXL exposure, corresponding to channel morphology and loss of skin integrity. Lasers Surg. Med. 49:348-354, 2017. © 2016 Wiley Periodicals, Inc.

AFL-dPDT is an effective treatment for patients with AK with extensive field cancerization, although AFL pretreatment is associated with intensified local skin reactions.

BackgroundThe current radiation threat from the Fukushima power plant accident has prompted rethinking of the contingency plan for prophylaxis and treatment of the acute radiation syndrome (ARS). The well-documented effect of the growth factors (granulocyte colony-stimulating factor [G-CSF] and granulocyte-macrophage colony-stimulating factor [GM-CSF]) in acute radiation injury has become standard treatment for ARS in the United States, based on the fact that growth factors increase number and functions of both macrophages and granulocytes.MethodsReview of the current literature.ResultsThe lungs have their own host defense system, based on alveolar macrophages. After radiation exposure to the lungs, resting macrophages can no longer be transformed, not even during systemic administration of growth factors because G-CSF/GM-CSF does not penetrate the alveoli. Under normal circumstances, locally-produced GM-CSF receptors transform resting macrophages into fully immunocompetent dendritic cells in the sealed-off pulmonary compartment. However, GM-CSF is not expressed in radiation injured tissue due to defervescence of the macrophages. In order to maintain the macrophage’s important role in host defense after radiation exposure, it is hypothesized that it is necessary to administer the drug exogenously in order to uphold the barrier against exogenous and endogenous infections and possibly prevent the potentially lethal systemic infection, which is the main cause of death in ARS.RecommendationPreemptive treatment should be initiated after suspected exposure of a radiation dose of at least <2 Gy by prompt dosing of 250–400 μg GM-CSF/m2 or 5 μg/kg G-CSF administered systemically and concomitant inhalation of GM-CSF < 300 mcg per day for at least 14–21 days.ConclusionThe present United States standard for prevention and treatment of ARS standard intervention should consequently be modified into the combined systemic administration of growth factors and inhaled GM-CSF to ensure the sustained systemic and pulmonary host defense and thus prevent pulmonary dysfunction.

Background and Objective: Recently, a novel acne treatment based on selective photothermolysis of pilosebaceous units with follicular delivery of inert gold microparticles as an exogenous chromophore and diode laser pulses has been developed. To evaluate the efficacy and safety of a single monotherapy treatment regimen with gold microparticles and diode laser exposure in patients with moderate and moderately severe acne. Further, to evaluate the added benefit of a second treatment regimen combined with pharmaceutical acne treatment in patients with inadequate initial response. Materials and Methods: Patients with moderate and moderately severe facial acne were recruited in this openlabel, pilot study. A single treatment regimen consisted of three weekly facial treatments with topically applied gold microparticles and diode laser pulses. Outcome measures were the proportion of patients with ≥40% improvement in number of acne lesions (weighted lesion count [WLC]) at 12 weeks (single treatment regimen, primary outcome measure), 24, and 36 weeks from baseline (two treatment regimens), safety, and patient satisfaction. Results: A total of 28 patients were enrolled in the study (18 males, 10 females, 19 patients with moderate acne severity, 9 with moderately severe, mean age: 19.8 years). Twenty-five patients underwent analysis for outcome measures. After a single monotherapy treatment regimen, 76% patients (19/25) achieved ≥40% reduction in WLC (mean WLC reduction: 63%; SD: 13%). Of the patients undergoing two treatment regimens (n = 9 patients), 56% experienced a reduction in acne lesion burden (WLC) ≥40% at 24 weeks and 89% 36 weeks post-baseline. Mean pain score was 4.0 (SD: 1.3), and transient erythema and perifollicular edema were commonly noted after treatment. Most patients (81%) were either "satisfied" or "very satisfied" with the treatment. Conclusion: Acne therapy based on selective photothermolysis with gold microparticles shows promise and may be used in treatment of moderate to moderately severe acne.

Under the current study conditions, PDT-induced skin reactions were unaffected by PBM. Lasers Surg. Med. 49:810-818, 2017. © 2017 Wiley Periodicals, Inc.