Energy-modulated x-ray fluorescence and luminescence emissions from therapeutic nanoparticles.

In this study, we have investigated the possibility of modulating x-ray fluorescence (XF) and x-ray luminescence (XL) emissions from therapeutic nanoparticles (NPs) by fine-tuning the energy of incident x-rays from benchtop x-ray sources. We have carried out detailed experimental studies to determine the strength of XF and XL emissions from Y2O3:Eu3+ and LaF3:Tb3+ NPs being irradiated with x-rays from benchtop x-ray sources operated with different tube-voltages and coupled to various filter configurations. These studies demonstrated that low-energy x-rays with average energy at around 10-15 keV are the most efficient to stimulate XL emission from the Y2O3:Eu3+ and LaF3:Tb3+ NPs. The efficiency falls quickly when x-ray energies go above or below the optimum energy range. As one would expect, x-rays with average energy just above the corresponding absorption edge of the target metal would be the most efficient in inducing XF emission. In this study, we have also demonstrated that one could fine-tune the incident x-ray energy to modulate the XL and XF emissions, such as (a) selectively inducing either XL or XF emission from the same type of NPs, (b) inducing preferential XL activation of Y2O3:Eu3+ over LaF3:Eu3+ or controlling the ratio of XL activation of these two types of NPs, and (c) introducing preferential XF emission from one type of NPs over the other. As a potential application, one could optimize the energy-characteristics of the incident x-rays to facilitate multiplexed combinatorial delivery of photodynamic therapy (X-PDT), where different agents could be administrated and then selectively activated in user-defined spatial and temporal patterns to fulfill combinatorial therapeutic effects. The understanding gained through this study could prove critical for enhancing the therapeutic delivery in X-PDT, and for attaining high-quality x-ray fluorescence computed tomography (XFCT) and x-ray luminescence computed tomography (XLCT) images while minimizing the x-ray dose to the sample.

A randomized, open-label, controlled trial to evaluate the antimicrobial and surgical effect of CO2 laser treatment in diabetic infected foot ulcers: DULCIS (diabetic ulcer, CO2 laser, and infections) study.

AIM: Debridement of fibrin and necrotic tissue from the ulcer surface is an important component of the treatment of diabetic ulcers. A possible alternative to standard lancets is represented by CO2 laser, which vaporizes necrotic tissues together with any pathogen. The present trial is aimed at verifying the effect of a CO2 laser on bacterial load in the debridement of infected diabetic foot ulcers. METHODS: In this open-label randomized controlled trial (NCT02677779), patients with diabetes and an infected foot ulcers were randomized to either CO2 laser or traditional debridement. RESULTS: The reduction (%) of bacterial load with CO2 laser was significantly greater than in control group [-99.9 (-100.0; -90.0) vs. -50.0 (-96.0; -75.0), p = 0.049]. Similarly, a significantly greater reduction (%) of the fraction of ulcer area covered by fibrin was obtained in the intervention group [-84.1 (-95.0; -72.2) vs. -46.9 (-69.5; -40.8), p = 0.038]. CONCLUSIONS: Debridement of ulcers with CO2 laser significantly reduces bacterial load and fibrin-covered areas, and could be of help in the treatment of diabetic foot ulcer.

CO2 laser for the treatment of diabetic foot ulcers with exposed bone. A consecutive series of type 2 diabetic patients.

AIM: The treatment of foot ulcers with exposed bone is challenging, because of the risk of infection and of difficulties in the development of granulation tissue. A CO2 laser beam could be used to produce discontinuities in periosteum, allowing the exposure of blood containing multipotent stem cells, capable of initiating the healing process. The local application of platelet-rich plasma (PRP) has been proposed as a therapeutic tool for accelerating healing in foot ulcers, including those in patients with diabetes. Aim of the present pilot, proof-of-concept study is the assessment of the therapeutic potential of CO2 laser treatment, either alone or combined with PRP, in the treatment of diabetic foot ulcers with exposed bone. METHODS: We performed a pilot, uncontrolled 3-month observation study on a consecutive series of 9 type two diabetic patients and foot ulcers with exposed bone. A CO2-laser was used for producing nine discontinuities on periosteum for each cm2, by directing the focused laser beam on the bone until bleeding. The procedure was repeated up to 6 times, at a distance of 1 week and ulcers assessed weekly until the end of the study (3 months). In the last 5 of the 14 patients, the treatment described above was associated with PRP. RESULTS: Of the nine patients treated, four healed, and one more patient developed granulation tissue covering entirely bone surface. Out of the four patients who did not heal, one underwent minor amputation. Among the five patients treated with a combination of CO2 laser and PRP, two healed within 3 months, and two more patients developed granulation tissue covering entirely bone surface; the fifth patient did not show any improvement and underwent amputation. CONCLUSIONS: The present pilot experience represents a novelty in this field showing a possible use of CO2-laser in the treatment of diabetic foot ulcers.