Non-Invasive Analysis of Actinic Keratosis before and after Topical Treatment Using a Cold Stimulation and Near-Infrared Spectroscopy

Background and objectives: The possible evolution of actinic keratoses (AKs) into invasive squamous cell carcinomas (SCC) makes their treatment and monitoring essential. AKs are typically monitored before and after treatment only through a visual analysis, lacking a quantitative measure to determine treatment effectiveness. Near-infrared spectroscopy (NIRS) is a non-invasive measure of the relative change of oxy-hemoglobin and deoxy-hemoglobin (O2Hb and HHb) in tissues. The aim of our study is to determine if a time and frequency analysis of the NIRS signals acquired from the skin lesion before and after a topical treatment can highlight quantitative differences between the AK skin lesion area. Materials and Methods: The NIRS signals were acquired from the skin lesions of twenty-two patients, with the same acquisition protocol: baseline signals, application of an ice pack near the lesion, removal of ice pack and acquisition of vascular recovery. We calculated 18 features from the NIRS signals, and we applied multivariate analysis of variance (MANOVA) to compare differences between the NIRS signals acquired before and after the therapy. Results: The MANOVA showed that the features computed on the NIRS signals before and after treatment could be considered as two statistically separate groups, after the ice pack removal. Conclusions: Overall, the NIRS technique with the cold stimulation may be useful to support non-invasive and quantitative lesion analysis and regression after a treatment. The results provide a baseline from which to further study skin lesions and the effects of various treatments

A microscale-based model for small-strain stiffness in unsaturated granular geomaterials

Stiffness at very small strains G 0 is commonly assessed by way of laboratory and field methods, and used to design a wide range of infrastructure. When stiffness is inferred from field measurements, its value depends on the soil suction and state of saturation at the time of the measurement, and models are needed to infer G 0 at varying suction and degree of saturation. When stiffness is measured on saturated specimens in the laboratory, models are needed to extrapolate the laboratory saturated' stiffness to the field unsaturated' stiffness. This paper presents an experimental investigation of G 0 of unsaturated sand using the hanging water column method and the bender element technique. Experimental results revealed that wave propagation velocity and, hence, stiffness is not controlled by the product suction times the degree of saturation'. A microscale-based model was formulated to interpret the experimental results, and to elucidate the mechanisms underlying different patterns of G 0 in unsaturated materials observed in the literature. According to the proposed model, the evolution of G 0 is controlled by the evolution of the suction/degree of saturation-induced intergranular stress during drying-wetting cycles. The breadth of the water retention curve and the magnitude of the intergranular stress due to the presence of the menisci were found to be responsible for the different patterns of G 0

Efficacy of new class I medical device for actinic keratoses: a randomized controlled prospective study

AbstractBackground: The presence of Actinic Keratoses (AKs) represent the most important warning sign of subclinical ultraviolet radiation. Currently, the regular use of sunscreens is considered es..

Exploring the micromechanics of non-active clays by way of virtual DEM experiments

The micromechanical behaviour of clays cannot be investigated experimentally in a direct fashion due to the small size of clay particles. An insight into clay mechanical behaviour at the particle scale can be gained by way of virtual experiments based on the discrete-element method (DEM). So far, most DEM models for clays have been designed on the basis of theoretical formulations of inter-particle interactions, with limited experimental evidence of their actual control over the clay's macroscopic response. This paper presents a simplified two-dimensional DEM framework where contact laws were inferred from indirect experimental evidence at the microscale provided by Pedrotti and Tarantino in 2017 (particle-to-particle interactions were probed experimentally by varying the pore-fluid chemistry, and the resulting effect was explored by way of scanning electron microscopy and mercury intrusion porosimetry). The proposed contact laws were successfully tested against their ability to reproduce qualitatively the compression behaviour of clay with pore fluids of varying pH and dielectric permittivity. The DEM framework presented in this work was intentionally kept simple in order to demonstrate the robustness of the micromechanical concept underlying the proposed contact laws. It is anticipated that a satisfactory quantitative prediction would be achieved by moving to a three-dimensional formulation, by considering polydisperse specimens and by refining the contact laws

AKASI and Near-Infrared Spectroscopy in the combined effectiveness evaluation of an actinic keratoses preventive product in immunocompetent and immunocompromised patients

Introduction: The high incidence of actinic keratoses among both the elderly population and immunocompromised subjects and the considerable risk of progression from in situ to invasive neoplasms makes it essential to identify new prevention, treatment, and monitoring strategies.Objective: The aim of this study was to evaluate the efficacy on AKs of a topical product ((R) Rilastil AK Repair 100 +) containing high-protection sunscreens, a DNA Repair Complex with antioxidant and repairing action against UV-induced DNA damage, and nicotinamide, a water-soluble derivative of vitamin B3 that demonstrated several photoprotective effects both in vitro and in vivo.Methods: The study enrolled 74 Caucasian patients, which included 42 immunocompetent and 32 immunosuppressed subjects. The efficacy of the treatment has been evaluated through the clinical index AKASI score and the non-invasive Near-Infrared Spectroscopy method.Results: The AKASI score proved to be a valid tool to verify the efficacy of the product under study, highlighting an average percentage reduction at the end of treatment of 31.37% in immunocompetent patients and 22.76% in organ transplant recipients, in comparison to the initial values, with a statistically significant reduction also in the single time intervals (T0 vs. T1 and T1 vs. T2) in both groups. On the contrary, the Near-Infrared Spectroscopy (a non-invasive technique that evaluates hemoglobin relative concentration variations) did not find significant differences for O(2)Hb and HHb signals before and after the treatment, probably because the active ingredients of the product under study can repair the photo-induced cell damage, but do not significantly modify the vascularization of the treated areas.Conclusion: The results deriving from this study demonstrate the efficacy of the product under study, confirming the usefulness of the AKASI score in monitoring treated patients. Near-Infrared Spectroscopy could represent an interesting strategy for AK patients monitoring, even if further large-scale studies will be needed

Teledermoscopy in the Diagnosis of Melanocytic and Non-Melanocytic Skin Lesions: NurugoTM Derma Smartphone Microscope as a Possible New Tool in Daily Clinical Practice

Background: Due to the COVID-19 pandemic, teledermoscopy has been increasingly used in the remote diagnosis of skin cancers. In a study conducted in 2020, we demonstrated a potential role of an inexpensive device (NurugoTM Derma) as a first triage to select the skin lesions that require a face-to-face consultation with dermatologists. Herein, we report the results of a novel study that aimed to better investigate the performance of NurugoTM. Objectives: (i) verify whether the NurugoTM can be a communication tool between the general practitioner (GP) and dermatologist in the first assessment of skin lesions, (ii) analyze the degree of diagnostic–therapeutic agreement between dermatologists, (iii) estimate the number of potentially serious diagnostic errors. Methods: One hundred and forty-four images of skin lesions were collected at the Dermatology Outpatient Clinic in Novara using a conventional dermatoscope (instrument F), the NurugoTM (instrument N), and the latter with the interposition of a laboratory slide (instrument V). The images were evaluated in-blind by four dermatologists, and each was asked to make a diagnosis and to specify a possible treatment. Results: Our data show that F gave higher agreement values for all dermatologists, concerning the real clinical diagnosis. Nevertheless, a medium/moderate agreement value was obtained also for N and V instruments and that can be considered encouraging and indicate that all examined tools can potentially be used for the first screening of skin lesions. The total amount of misclassified lesions was limited (especially with the V tool), with up to nine malignant lesions wrongly classified as benign. Conclusions: NurugoTM, with adequate training, can be used to build a specific support network between GP and dermatologist or between dermatologists. Furthermore, its use could be extended to the diagnosis and follow-up of other skin diseases, especially for frail patients in emergencies, such as the current pandemic context

A diabetic milieu increases ACE2 expression and cellular susceptibility to SARS-CoV-2 infections in human kidney organoids and patient cells

Altres ajuts: European Research Council (ERC); EIT Health under grant ID 20366 (R2U-Tox-Assay); IBEC Faster Future program (A por la COVID-19); European Regional Development Fund (FEDER); Gobierno de Navarra, Departamento de Desarrollo Económico y Empresarial (AGATA 0011-1411-2020-000011, DIANA 0011-1411-2017-000029); Ministerio de Economía y Competitividad (MINECO); IBEC International PhD Programme "La Caixa" Severo Ochoa fellowships (LCF/BQ/SO16/52270019); start-up funds from the College of Medicine at the University of Florida, Gainesville; T. von Zastrow Foundation; the FWF Wittgenstein award (Z 271-B19); the Austrian Academy of Sciences and the Canada 150 Research Chairs Program (F18-01336); the Canadian Institutes of Health Research COVID-19 (F20-02343, F20-02015); Swiss National Science Foundation fellowship (P400PM_194473/1); Swedish Research Council (2018-05766); the Innovative Medicines Initiative 2 Joint Undertaking (JU 101005026); Ayudas Fundación BBVA a Equipos de Investigación Científica SARS-CoV-2 y COVID-19 through the project "Identifying SARS-CoV-2-host cell interactions exploiting CRISPR-Cas9-engineered human organoids: through the development of specific therapies against COVID19"; Fundació la Marató de TV3 (201910-31 and 202125-3).It is not well understood why diabetic individuals are more prone to develop severe COVID-19. To this, we here established a human kidney organoid model promoting early hallmarks of diabetic kidney disease development. Upon SARS-CoV-2 infection, diabetic-like kidney organoids exhibited higher viral loads compared with their control counterparts. Genetic deletion of the angiotensin-converting enzyme 2 (ACE2) in kidney organoids under control or diabetic-like conditions prevented viral detection. Moreover, cells isolated from kidney biopsies from diabetic patients exhibited altered mitochondrial respiration and enhanced glycolysis, resulting in higher SARS-CoV-2 infections compared with non-diabetic cells. Conversely, the exposure of patient cells to dichloroacetate (DCA), an inhibitor of aerobic glycolysis, resulted in reduced SARS-CoV-2 infections. Our results provide insights into the identification of diabetic-induced metabolic programming in the kidney as a critical event increasing SARS-CoV-2 infection susceptibility, opening the door to the identification of new interventions in COVID-19 pathogenesis targeting energy metabolism

Fatality rate and predictors of mortality in an Italian cohort of hospitalized COVID-19 patients

Clinical features and natural history of coronavirus disease 2019 (COVID-19) differ widely among different countries and during different phases of the pandemia. Here, we aimed to evaluate the case fatality rate (CFR) and to identify predictors of mortality in a cohort of COVID-19 patients admitted to three hospitals of Northern Italy between March 1 and April 28, 2020. All these patients had a confirmed diagnosis of SARS-CoV-2 infection by molecular methods. During the study period 504/1697 patients died; thus, overall CFR was 29.7%. We looked for predictors of mortality in a subgroup of 486 patients (239 males, 59%; median age 71 years) for whom sufficient clinical data were available at data cut-off. Among the demographic and clinical variables considered, age, a diagnosis of cancer, obesity and current smoking independently predicted mortality. When laboratory data were added to the model in a further subgroup of patients, age, the diagnosis of cancer, and the baseline PaO2/FiO2 ratio were identified as independent predictors of mortality. In conclusion, the CFR of hospitalized patients in Northern Italy during the ascending phase of the COVID-19 pandemic approached 30%. The identification of mortality predictors might contribute to better stratification of individual patient risk

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Micromechanics of non-active clays in saturated state and DEM modelling

The paper presents a conceptual micromechanical model for 1-D compression behaviour of non-active clays in saturated state. An experimental investigation was carried out on kaolin clay samples saturated with fluids of different pH and dielectric permittivity. The effect of pore fluid characteristics on one-dimensional compressibility behaviour of kaolin was investigated. A three dimensional Discrete Element Method (DEM) was implemented in order to simulate the response of saturated kaolin observed during the experiments. A complex contact model was introduced, considering both the mechanical and physico-chemical microscopic interactions between clay particles. A simple analysis with spherical particles only was performed as a preliminary step in the DEM study in the elastic regime