Pso-Reg: a web registry for psoriasis in real life.

BACKGROUND: Psoriasis (PsO) is a common immune mediated inflammatory disease, affecting about 60 million people worldwide. Although current therapies have dramatically changed the therapeutic approach to the disease, the heterogeneity of responses often results in an essential unmet clinical need. This study describes the design and development of the Psoriasis Registry (Pso-Reg), an Italian electronic-based-registry, aimed to collect real life data of patients with psoriasis. METHODS: Pso-Reg is a multicenter, retrospective and observational cohort study based on the Research Electronic Data Capture (REDcap) tool. Five Italian medical centres were part of the network and all patients affected by PsO were included in the study. Socio-demographic, clinical characteristics, laboratory findings and therapies were collected, and descriptive analysis was carried out. RESULTS: Among the 768 patients analyzed, 446 were men (58.1%), with a mean age of 55.5 years. The first more frequent comorbidity was psoriatic arthritis (26.8%), followed by hypertension (25.3%), diabetes (10%) and dyslipidemia (11.7%). Of the entire cohort, 240 patients (38.2%) had a positive family history for PsO. Vulgar type was the most common phenotype (85.5%), with a major involvement of the scalp (13.8%). The mean PASI (Psoriasis Area Severity Index) score at the baseline was 7.5 (7.8). At the enrolment, 107 patients were treated with topic treatments (13.9%), 5 with phototherapy (0.7%), 92 with cDMARDs (conventional disease-modifying anti-rheumatic drugs) (12.0%) and 471 with biologic therapies (61.3%). CONCLUSIONS: Real-life data from Pso-Reg could contribute providing the rationale for an individual-based strategy and a more tailored approach for the management of psoriasis.

The role of dosimetry and biological effects in metastatic castration-resistant prostate cancer (mCRPC) patients treated with 223Ra: first in human study.

BACKGROUND: 223Ra is currently used for treatment of metastatic castration resistant prostate cancer patients (mCRPC) bone metastases with fixed standard activity. Individualized treatments, based on adsorbed dose (AD) in target and non-target tissue, are absolutely needed to optimize efficacy while reducing toxicity of α-emitter targeted therapy. This is a pilot first in human clinical trial aimed to correlate dosimetry, clinical response and biological side effects to personalize 223Ra treatment. METHODS: Out of 20 mCRPC patients who underwent standard 223Ra treatment and dosimetry, in a subset of 5 patients the AD to target and non-target tissues was correlated with clinical effects and radiation-induced chromosome damages. Before each 223Ra administrations, haematological parameters, PSA and ALP values were evaluated. Additional blood samples were obtained baseline (T0), at 7 days (T7), 30 days (T30) and 180 days (T180) to evaluate chromosome damage. After administration WB planar 223Ra images were obtained at 2-4 and 18-24 h. Treatment response and toxicity were monitored with clinical evaluation, bone scan, 18F-choline-PET/CT, PSA value and ALP while haematological parameters were evaluated weekly after 223Ra injection and 2 months after last cycle. RESULTS: 1. a correlation between AD to target and clinical response was evidenced with threshold of 20 Gy as a cut-off to obtain tumor control; 2. the AD to red marrow was lower than 2 Gy in all the patients with no apparently correlation between dosimetry and clinical toxicity. 3. a high dose dependent increase of the number of dicentrics and micronuclei during the course of 223Ra therapy was observed and a linear correlation has been found between blood AD (BAD) and number of dicentrics. CONCLUSIONS: This study provides some interesting preliminary evidence to be further investigated: dosimetry may be useful to identify a more appropriate 223Ra administered activity predicting AD to target tissue; a dose dependent complex chromosome damage occurs during 223Ra administration and this injury is more evident in heavily pre-treated patients; dosimetry could be used for radioprotection purpose. TRIAL REGISTRATION: The pilot study has been approved from the Ethics Committee of Regina Elena National Cancer Institute (N:RS1083/18-2111).

Wound Management Strategy for Treatment of Localized Cutaneous Leishmaniasis Using the TIME Framework.

INTRODUCTION: The current drugs available for the treatment of cutaneous leishmaniasis (CL) often cause several adverse events, and the risk-benefit ratio is low due to the risk of severe complications. Current treatment recommendations are based on data from areas endemic for leishmaniasis and are not always perfectly applicable, especially in cases of imported CL. Thus, it is crucial to assess the level of severity in each case to provide the most appropriate treatment modality. The World Health Organization recommends simple wound care (with unspecified strategies) or local therapy as first-line treatment. Systemic treatments should be reserved for selected patients. Additionally, there is little evidence in the literature regarding local treatments, such as paromomycin ointments, imiquimod, local infiltration with antimonials, and physical treatments such as cryotherapy or thermotherapy. OBJECTIVE: The authors report the use of the tissue debridement, infection/inflammation management, moisture balance, and edge assessment (TIME) model of wound bed preparation in a case of localized ulcerated CL. CASE REPORT: A 32-year-old female developed ulcerated nodules at the sites of insect bites that occurred during a trip to Columbia and was diagnosed with localized CL. Wound management included daily wound bed cleansing, surgical debridement, and antimicrobial and secondary polyurethane foam dressings. The lesions completely healed in 30 days. CONCLUSIONS: In the present case, the TIME approach simplified the local management of ulcerated CL, thereby improving both the healing process and cosmetic outcome. Further studies with a placebo-controlled group will be necessary to confirm the data.

Triticum vulgare Extract Modulates Protein-Kinase B and Matrix Metalloproteinases 9 Protein Expression in BV-2 Cells: Bioactivity on Inflammatory Pathway Associated with Molecular Mechanism Wound Healing.

Matrix metalloproteinases (MMPs) are a large family of ubiquitously expressed zinc-dependent enzymes with proteolitic activities. They are expressed in physiological situations and pathological conditions involving inflammatory processes including epithelial to mesenchymal transition (EMT), neuronal injury, and cancer. There is also evidence that MMPs regulate inflammation in tumor microenvironment, which plays an important role in healing tissue processes. Looking at both inflammatory and neuronal damages, MMP9 is involved in both processes and their modulation seems to be regulated by two proteins: tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 (IL-6). However other important genes are involved in molecular regulation of transcription factors, protein-kinase B (AKT), and p65. In addition, Triticum vulgare extract (TVE) modulated the biological markers associated with inflammatory processes, including p65 protein. While there are no evidence that TVE might be involved in the biological modulation of other inflammatory marker as AKT, we would like to assess whether TVE is able to (1) modulate phosphorylation of AKT (pAKT) as an early marker of inflammatory process in vitro and (2) affect MMP9 protein expression in an in vitro model. The BV-2 cells (microglial of mouse) have been used as an in vitro model to simulate both inflammatory and neuronal injury pathologies. Here, MMP9 seems to be involved in cellular migration through inflammatory marker activation. We simulate an inflammatory preclinical model treating BV-2 cells with lipopolysaccharide (LPS) to induce proinflammatory activation affecting pAKT and p65 proteins. TVE is revealed to restore the native expression of AKT and p65. Additionally, TVE extract modulates also the protein concentration of MMP9. Nevertheless, immunofluorescence confocal analyses revealed that both AKT and MMP9 are regulated together, synchronously. This work seems to demonstrate that two important genes can be used to monitor the beginning of an inflammatory process, AKT and MMP9, in which TVE seems able to modulate their expression of inflammation-associated molecules.

Biomodulation induced by fluorescent light energy versus standard of care in venous leg ulcers: a retrospective study.

OBJECTIVE: The recently completed EUREKA study confirmed the efficacy and safety profile of fluorescent light energy (FLE) in treating hard-to-heal wounds. To supplement the EUREKA prospective, observational, uncontrolled trial results, researchers selected one of the EUREKA clinical centres to conduct a retrospective analysis of matching wound care data for 46 venous leg ulcers (VLU) patients who had received standard wound care over a five-year period, compared with 10 EUREKA VLU subjects. METHOD: The study centre selected 46 patients with VLUs based on the matching criteria (wound age and size, patient's age and gender). They compared the healing rates of these matching VLUs with 10 VLU patients treated at the same centre during the EUREKA study. RESULTS: The EUREKA patients had larger and significantly older wounds (p<0.05) and significantly more risk factors (p<0.05) than the matching wounds. However, they had better outcomes (EUREKA: 40% versus matching group: 7% for full wound closure by 16 weeks). No wound breakdown was observed at 16 weeks in the EUREKA group, compared with 25% in the matching group. No EUREKA patient developed infections requiring antibiotics, compared with 37% in the matching group. EUREKA wounds had a mean relative wound area regression (RWAR) of 32% at week six and 50% at week 16, compared with -3% at week six and -6% at week 16 for the matching group. CONCLUSION: These findings show that the system based on FLE was well-tolerated and efficacious, with better clinical outcome results compared with the wounds analysed in this retrospective matching study and treated with standard of care alone.

Evaluation of fluorescence biomodulation in the real-life management of chronic wounds: the EUREKA trial.

OBJECTIVE: Fluorescence biomodulation (FB), a form of photobiomodulation (PBM) that is also known as low energy level light (LELL), has become an increasingly used clinical tool to induce wound healing in wounds that remain recalcitrant to treatment. In a real-life clinical setting, the aim of the EUREKA (EvalUation of Real-lifE use of Klox biophotonic system in chronic wound mAnagement) study was to confirm the efficacy and safety of LumiHeal, a system based on FB, in the treatment of chronic wounds such as venous leg ulcers (VLUs), diabetic foot ulcers (DFUs) and pressure ulcers (PUs). The effects of this FB system on the modulation of wound healing in chronic ulcers through FB induction were previously examined in an interim analysis of this study. METHOD: A multicenter, prospective, observational, uncontrolled trial in 12 clinical sites in Italy. The wound was cleansed with saline and a 2mm thick layer of a chromophore gel was applied to the affected area in a biweekly regimen. The area was then illuminated with the LED activator for five minutes at a distance of 5cm. Treatment was used in combination with standard of care specific to each type of chronic wound (VLU, DFU, PU). Wound area evaluation was assessed using the Silhouette Imaging System and quality of life (QoL) with the Cardiff Wound Impact Schedule (CWIS). A seven-point evaluation of the clinicans' view was also examined. RESULTS: We enrolled 100 subjects, with the final analysis including 99 patients/ulcers consisting of 52 VLUs, 32 DFUs and 15 PUs. Total wound closure at the end of the study was achieved in 47 patients by aetiology: 26 VLUs (50% of VLUs); 16 DFUs (50% of DFUs); and five PUs (33.3% of PUs). The mean wound area regression at last study assessment was significant for VLUs (41.0%; p<0.001) and DFUs (52.4%; p<0.001). After four weeks of treatment, it was possible to significantly predict if the ulcer would respond (defined as a decrease of wound size) to the study treatment. Adherence was high (95.2%) and no related serious adverse events were reported during the study. QoL significantly improved, with an increase of 15.4% of the total score, using the CWIS (p<0.001). CONCLUSION: The study confirmed a positive efficacy profile of the FB system in inducing the wound healing process in three different types of hard-to-heal chronic wounds. The treatment was shown to be safe and well tolerated by the patients, with a significant improvement in patient QoL. This approach offers an effective modality for the treatment of hard-to-heal chronic ulcers.

EUREKA study - the evaluation of real-life use of a biophotonic system in chronic wound management: an interim analysis.

OBJECTIVE: Interest has grown regarding photobiomodulation (PBM) with low-level light therapy, which has been shown to positively affect the stages of the wound healing process. In a real-life context clinical setting, the objective of the EUREKA study was to investigate efficacy, safety, and quality of life associated with the use of a BioPhotonic gel (LumiHeal™) in the treatment of chronic wounds such as venous leg ulcers (VLUs), diabetic foot ulcers (DFUs), and pressure ulcers (PUs). This BioPhotonic gel represents a new, first-in-class emission spectrum of light, including fluorescence, to induce PBM and modulate healing. DESIGN: The multicenter, prospective, interventional, uncontrolled, open-label study enrolled 100 patients in 12 wound centers in Italy. We performed an early interim analysis based on the first 33 subjects (13 VLU, 17 DFU, 3 PU) in seven centers who completed the study. MAIN RESULTS: Seventeen patients (52%) achieved total wound closure (full re-epithelialization for 2 weeks) during the study period. Two patients (6%) were considered "almost closed" (decrease of the wound area of more than 90% at study end) and three others (9%) were considered "ready for skin grafting". No related serious adverse events were observed, and the compliance was excellent. After the treatment, the average time to "pain-free" was 11.9 days in the VLU group. Quality of life was improved with overall increase of 26.4% of the total score (Cardiff Wound Impact Schedule, p=0.001). CONCLUSION: The study revealed a positive efficacy profile of the BioPhotonic gel in promoting wound healing and reactivating the healing process in different types of chronic, hard-to-heal wounds. The treatment was shown to be safe and well tolerated by the patients, and a reduction of pain perception was also detected during the treatment period. The improvement of the quality of life was accompanied by a high level of clinician satisfaction.

Clinical evaluation of the efficacy and safety of a medical device in various forms containing Triticum vulgare for the treatment of venous leg ulcers - a randomized pilot study.

This study was carried out to assess the efficacy and tolerability of the topical application of an aqueous extract of Triticum vulgare (TV) in different vehicles (cream, impregnated gauzes, foam, hydrogel, and dressing gel) for the treatment of venous lower leg ulcers. Fifty patients were randomized to receive one of the five investigational vehicles. Treatment was performed up to complete healing or to a maximum of 29 days. The wound size reduction from baseline was the primary efficacy variable, which was measured by means of a noninvasive laser scanner instrument for wound assessment. In all groups, apart from the foam group, a similar trend toward the reduction of the surface area was observed. The cream showed the greatest effect on the mean reduction of the lesion size. At last visit, six ulcers were healed: two in the cream group, three in the gauze group, and one in the dressing gel group. In the patients treated with the cream, the gauzes, the hydrogel, and the dressing gel, the reduction of lesion size was 40%-50%; the reduction was smaller in the foam group. No impact in terms of age on the healing process was found. The Total Symptoms Score decreased in all groups during the study; a greater efficacy in terms of signs/symptoms was observed in the patients treated with the gauzes. In the dressing gel group, one patient had an infection of the wound after 3 weeks of treatment and 2 of colonization, leading to a systemic antibiotic treatment. The events were judged as nonrelated to the device used. On the basis of the results, it could be argued that the medical device may be useful in the treatment of chronic venous ulcers.