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.

Review article: the pathogenesis of fibrosis in non-alcoholic steatohepatitis.

Non-alcoholic steatohepatitis has been recognized as a significant cause of end-stage liver disease and hepatic decompensation. Despite the growing interest in this condition, the molecular mechanisms underlying the development of fibrosis in this setting are only partially understood. In this article, the cellular and molecular basis of fibrosis in chronic liver disease are briefly outlined. In addition, mechanisms specifically operating in the context of fatty liver and steatohepatitis are examined, including: insulin resistance, oxidative stress, and inflammation. Finally, recent developments indicating the possible contribution of cytokines derived from adipose tissue (adipokines) to liver fibrosis is discussed.

Adipokines and liver fibrosis.

Liver fibrosis involves different cell types, and should be regarded as a "wound healing" response that occurres in conditions of chronic liver injury and is characterized by inflammation, activation of matrix-producing cells, matrix deposition and remodeling, and epithelial cell regeneration or an attempt thereof. Liver damage may be caused by several agents or conditions, resulting in different degrees and types of tissue inflammation and in activation of matrix-producing cells, such as the hepatic stellate cells (HSC). HSC undergo a phenotypic transition (known as "activation") to myofibroblast-like cells that synthesize different extracellular matrix components. Obesity is associated with the development of NASH, and has been indicated as an independent factor for the progression to fibrosis. In liver diseases, the biologic actions of the adipokines, such as leptin, adiponectin and resistin, released by adipocytes or locally produced by liver and/or inflammatory cells, may contribute to clarify the mechanisms of progression in NASH. The clinical and experimental findings accumulating on this class of molecules could represent the basis to devise a better management strategy for the patients with chronic liver disease.