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Background and objectivePulsed dye laser (PDL) treatment of cutaneous vascular lesions is associated with variable and unpredictable efficacy. Thus, alternative treatment modalities are needed. Previous in vitro and in vivo studies have demonstrated enhanced selective vascular destruction with benzoporphyrin derivative (BPD) monoacid ring A photodynamic therapy (PDT) followed immediately by PDL irradiation (PDT+PDL). Here, we evaluate PDT alone, PDL alone, and PDT+PDL protocols using an optimized in vivo rodent dorsal window chamber model.Study design/materials and methodsA dorsal window chamber was surgically installed on male Golden Syrian hamsters. BPD solution was administered intravenously via a jugular venous catheter. Evaluated interventions included: (1) Control (no BPD, no light); (2) Control (BPD, no light); (3) PDT alone (lambda = 576 nm; 25, 50, 75, or 96 J/cm2 radiant exposure; 15 minutes post-BPD injection); (4) PDL alone at 7 J/cm2 (585 nm, 1.5 milliseconds pulse duration, 7 mm spot); and (5) PDT (25 or 75 J/cm2)+PDL (7 J/cm2). Laser speckle imaging was used to monitor blood flow dynamics before, immediately after, and 1, 3, and 5 days post-intervention.ResultsPerfusion reduction on day 1 post-intervention was achieved with PDT>50 J/cm2, PDL alone, and PDT+PDL. However, by day 5 post-intervention, recovery of flow was observed with PDT alone at 50 J/cm2 (-15.1%) and PDL alone (+215%). PDT (75 J/cm2)+PDL resulted in the greatest prolonged reduction in vascular perfusion (-99.8%).ConclusionsOur in vivo data suggest that the PDT+PDL therapeutic protocol can result in enhanced and persistent vascular shutdown compared to PDT or PDL alone. The PDT+PDL approach has potential for considerable superficial vascular destruction and should be considered as a treatment modality for cutaneous vascular lesions. Monitoring of blood flow changes for as long as possible is crucial for accurate assessment of light-based vascular interventions.

We employ speckle imaging and window chamber models to study vascular remodeling processes after light-based therapies. Our data demonstrate that the response involves substantial remodeling over a monitoring period of up to 30 days post-intervention. © 2007 Optical Society of America.

Noninvasive blood flow characterization is essential to assess the health status of biological tissue and to evaluate the efficacy of therapies which target the microvasculature. Optimization of laser therapy for disfiguring vascular birthmarks is one specific clinical application. Current treatment protocols involve the use of high-power pulsed laser irradiation with parameters selected to induce selective photocoagulation of the targeted blood vessels. Protocol design is based largely on results from numerical modeling studies, which have predictive capability of the laser light distribution within the skin and subsequent photothermal response leading towards selective photocoagulation. However, the biological response of the microvasculature to therapeutic laser intervention remains a poorly-researched field. We hypothesize that the acute photothermal response of the microvasculature is a poor predictor of the chronic response, due to vascular remodeling processes which are not included in current modeling studies. To test this hypothesis, we employ an optical imaging method to assess blood flow dynamics in response to therapeutic intervention.

Objective: To assess whether patients with psoriasis treated with tumor necrosis factor (TNF) inhibitors have a decreased risk of myocardial infarction (Ml) compared with those not treated with TNF inhibitors. Design: Retrospective cohort study. Setting: Kaiser Permanente Southern California health plan. Patients: Patients with at least 3 International Classification of Diseases, Ninth Revision, Clinical Modification, codes for psoriasis (696.1) or psoriatic arthritis (696.0) (without antecedent Ml) between January 1, 2004, and November 30, 2010. Main Outcome Measure: Incident Ml. Results: Of 8845 patients included, 1673 received a TNF inhibitor for at least 2 months (TNF inhibitor cohort), 2097 were TNF inhibitor naive and received other systemic agents or phototherapy (oral/phototherapy cohort), and 5075 were not treated with TNF inhibitors, other systemic therapies, or phototherapy (topical cohort). The median duration of follow-up was 4.3 years (interquartile range, 2.9, 5.5 years), and the median duration of TNF inhibitor therapy was 685 days (interquartile range, 215, 1312 days). After adjusting for Ml risk factors, the TNF inhibitor cohort had a significantly lower hazard of Ml compared with the topical cohort (adjusted hazard ratio, 0.50; 95% CI, 0.32-0.79). The incidence of Ml in the TNF inhibitor, oral/phototherapy, and topical cohorts were 3.05, 3.85, and 6.73 per 1000 patient-years, respectively. Conclusions: Use of TNF inhibitors for psoriasis was associated with a significant reduction in Ml risk and incident rate compared with treatment with topical agents. Use of TNF inhibitors for psoriasis was associated with a non-statistically significant lower Ml incident rate compared with treatment with oral agents/phototherapy. [ABSTRACT FROM AUTHOR]

Psoriasis (PsO) and psoriatic arthritis (PsA) are chronic T cell-mediated inflammatory diseases that manifest not only in the skin and joints but also in the form of cardiometabolic disturbances, which include insulin resistance, dyslipidemia, and obesity. Thus, PsO and PsA patients are predisposed to metabolic syndrome (MetS), diabetes, and cardiovascular disease. In recent years, the introduction of targeted therapy in the form of tumor necrosis factor-alpha (TNF-alpha) antagonists, such as infliximab, etanercept, and adalimumab has been an important and effective addition to the treatment armamentarium for PsO and PsA. Although TNF-alpha antagonists have produced promising results clinically in reducing cutaneous and joint manifestations of PsO and PsA, their effects on MetS components in these patients are presently unclear. This review summarizes the current limited evidence on the effects of TNF-alpha antagonists on MetS components in PsO and PsA patients and extrapolates from related literature in rheumatoid arthritis, which is also a T cell-mediated inflammatory disease, for additional information.