IGF1 synthesis after CO2 fractional laser resurfacing (FLR): New insights in the treatment of scalp actinic keratoses

ObjectivesActinic keratosis have a high risk of progression to a squamous cell carcinoma. Insulin-like growth factor 1 and its receptor play a relevant role in restoring repair of ultraviolet-induced cell damage. This pathway is reduced in patients older than 65 years. Ablative fractional laser resurfacing could normalize insulin-like growth factor 1 (IGF-1) secretion in elderly by recruiting new fibroblasts. The aim of the study is to evaluate restoration of IGF1 values by PCR in senescent fibroblasts after ablative fractional laser resurfacing. MethodsWe enrolled 30 male patients with multiple actinic keratosis on the scalp, equally divided into two mirror areas of up to 50 cm(2), treating only the right one. We performed one skin biopsy for each area 30 days after treatment. Real-time PCR in fibroblasts was performed to assess the change in IGF1. At baseline and after 6 months, in vivo reflectance confocal microscopy examination was performed in all patients. ResultsIGF1 values were increased in the treated side by about 60%. The right areas had fairly complete resolution of actinic keratosis at the last follow-up visit after 6 months with no appearance of new lesions. The mean number of actinic keratosis in the right area was reduced by more than 75% at four- and six-follow-up visits compared to the left area. The improvement in the right area was also evidenced by lower values of the mean AKASI (actinic keratosis area and severity index) score. Reflectance confocal microscopy showed a reduction of keratinocytic disarray and scales after treatment. DiscussionTaken together, all the clinical, laboratory, and in vivo results of our study allowed us to confirm that ablative fractional laser resurfacing is a valuable tool for the treatment of actinic keratosis and cancerization field, both for the management of clinically evident lesions and for preventing the occurrence of squamous cell carcinoma

Deep Learning Techniques for the Dermoscopic Differential Diagnosis of Benign/Malignant Melanocytic Skin Lesions: From the Past to the Present

There has been growing scientific interest in the research field of deep learning techniques applied to skin cancer diagnosis in the last decade. Though encouraging data have been globally reported, several discrepancies have been observed in terms of study methodology, result presentations and validation in clinical settings. The present review aimed to screen the scientific literature on the application of DL techniques to dermoscopic melanoma/nevi differential diagnosis and extrapolate those original studies adequately by reporting on a DL model, comparing them among clinicians and/or another DL architecture. The second aim was to examine those studies together according to a standard set of statistical measures, and the third was to provide dermatologists with a comprehensive explanation and definition of the most used artificial intelligence (AI) terms to better/further understand the scientific literature on this topic and, in parallel, to be updated on the newest applications in the medical dermatologic field, along with a historical perspective. After screening nearly 2000 records, a subset of 54 was selected. Comparing the 20 studies reporting on convolutional neural network (CNN)/deep convolutional neural network (DCNN) models, we have a scenario of highly performant DL algorithms, especially in terms of low false positive results, with average values of accuracy (83.99%), sensitivity (77.74%), and specificity (80.61%). Looking at the comparison with diagnoses by clinicians (13 studies), the main difference relies on the specificity values, with a +15.63% increase for the CNN/DCNN models (average specificity of 84.87%) compared to humans (average specificity of 64.24%) with a 14,85% gap in average accuracy; the sensitivity values were comparable (79.77% for DL and 79.78% for humans). To obtain higher diagnostic accuracy and feasibility in clinical practice, rather than in experimental retrospective settings, future DL models should be based on a large dataset integrating dermoscopic images with relevant clinical and anamnestic data that is prospectively tested and adequately compared with physicians

Prospective monitoring of Chronic Myeloid Leukemia Patients from Time of TKI Discontinuation: the fate of Peripheral Blood CD26+ Leukemia Stem Cells

Introduction: In chronic myeloid leukemia (CML), about half of the patients achieving a deep and stable molecular response with tyrosine kinase inhibitors (TKIs) may discontinue TKI treatment without disease recurrence. As such, treatment-free remission (TFR) has become an ambitious goal of treatment. Given the evidence that deepness and duration of molecular response are necessary but not sufficient requisites for a successful TFR, additional biological criteria are needed to identify CML patients suitable for efficacious discontinuation. Leukemia stem cells (LSCs) are supposed to be the reservoir of the disease. Previously, we demonstrated that residual circulating CD34+/CD38-/CD26+ LSCs were still detectable in a consistent number of CML patients during TFR.Methods: CML LSCs could be easily identified by flow-cytometry as they express the CD34+/CD38-/CD26+ phenotype. In this study, we explored the role of these cells and their correlation with molecular response in a cohort of 109 consecutive chronic phase CML patients prospectively monitored from the time of TKI discontinuation.Results: After a median observation time of 33 months from TKI discontinuation, 38/109 (35%) patients failed TFR after a median time of 4 months, while 71/109 (65%) patients are still in TFR. At TKI discontinuation, peripheral blood CD26+LSCs were undetectable in 48/109 (44%) patients and detectable in 61/109 (56%). No statistically significant correlation between detectable/undetectable CD26+LSCs and the rate of TFR loss was found (p = 0.616). The incidence of TFR loss based on the type of TKI treatment was statistically significant for imatinib treatment compared to that of nilotinib (p = 0.039). Exploring the behavior of CD26+LSCs during TFR, we observed fluctuating values that were very variable between patients, and they were not predictive of TFR loss.Discussion: Up to date, our results confirm that CD26+LSCs are detectable at the time of TKI discontinuation and during TFR. Moreover, at least for the observation median time of the study, the persistence of "fluctuating" values of residual CD26+LSCs does not hamper the possibility to maintain a stable TFR. On the contrary, even patients discontinuing TKI with undetectable CD26+LSCs could undergo TFR loss. Our results suggest that factors other than residual LSCs "burden" playing an active role in controlling disease recurrence. Additional studies evaluating CD26+LSCs' ability to modulate the immune system and their interaction in CML patients with very long stable TFR are ongoing

Super-High Magnification Dermoscopy Can Help for the Diagnosis of Lentigo Maligna: a Pilot Study on 61 Cases

Introduction: Facial lentigo maligna/lentigo maligna melanoma (LM/LMM) is a significant diagnostic clinical challenge and dermoscopy can help its diagnosis. Objectives: The following study aimed to evaluate if super-high magnification dermoscopy at 400x can add further details for the diagnosis of the LM/LMM. Methods: This is a retrospective observational, multicentric study enrolling patients who received a 20x and 400x (D400) magnification dermoscopic examination of facial skin lesions in clinical differential diagnosis with LM/LMM. Dermoscopic images were retrospectively evaluated by four observers for the presence/absence of nine 20x and ten 400x dermoscopic features. Univariate and multivariate analyses were carried out to find predictors of LM/LMM. Results: We enrolled 61 patients with a single atypical skin lesion of the face, including 23 LMs and 3 LMMs. The presence of roundish and/or dendritic melanocytes (P < 0.001), irregular arrangement of melanocytes (P <0.001), irregular in shape and size melanocytes (P = 0.002), and folliculotropism of melanocytes (P <0.001) at D400 were more frequent in LM/LMM than other facial lesions. According to the multivariate analysis, roundish melanocytes at 400x dermoscopy were more indicative of LM/LMM (Odds Ratio-OR 49.25, 95% CI 8.75-513.2, P < 0.001), and sharply demarcated borders at 20x dermoscopy were more indicative of not-LM/LMM (OR 0.1, 95% CI 0.01-0.79, P = 0.038). Conclusions: D400 can identify atypical melanocyte proliferation and folliculotropism that can help to identify LM/LMM together with conventional dermoscopy data. Our preliminary observations should be confirmed by larger studies

Doppler and Spectral Ultrasound of Sacroiliac Joints in Pediatric Patients with Suspected Juvenile Spondyloarthritis

Background: Power Doppler ultrasound (PDUS) with spectral wave analysis (SWA) has been compared with magnetic resonance imaging (MRI) in documenting active sacroiliitis in early spondyloarthritis (SpA) but, to date, PDUS/SWA has not been yet applied to the study of sacroiliac joints (SIJs) in children. Methods: A group of 20 children (13 F/7 M, mean age 14.2 y) with suspected juvenile SpA (jSpA) underwent PDUS/SWA and, subsequently, MRI of the SIJs. SIJs PDUS scoring and resistance index (RI) of the SIJs flows were recorded. The accuracy of PDUS/SWA for the diagnosis of active sacroiliitis was evaluated, with MRI as the gold standard. Results: PDUS signals were detected in 19 patients and 30 SIJs. Bone marrow edema (BME) lesions on MRI were detected in 12 patients (diagnosed as jSpA) and 22 SIJs. PDUS scoring on SIJs were higher in patients with a final diagnosis of jSpA (p = 0.003). On SWA, the mean RIs in patients with or without final diagnosis of active sacroiliitis were, respectively, 0.604 and 0.767 (p = 0.005) at joint level. A RI &lt; 0.55 and PDUS &gt; 1 showed the higher specificity for sacroiliitis (AUROC curve 0.854 for PDUS and 0.920 for RI). SIJs PDUS/SWA showed an overall concordance of 82.35%, with substantial agreement (k = 0.627) with MRI on the diagnosis of sacroiliitis. Conclusions: In children with sacroiliitis, PDUS demonstrates a rich vascularization into SIJs and low RIs (&lt;0.55) have high specificity for this condition. SIJs PDUS/SWA could be useful as a screening method in children with suspected jSpA

Transient hypogonadism is associated with heart rate-corrected QT prolongation and torsades de pointes risk during active systemic inflammation in men

Background Systemic inflammation and male hypogonadism are 2 increasingly recognized "nonconventional" risk factors for long-QT syndrome and torsades de pointes (TdP). Specifically, inflammatory cytokines prolong, while testosterone shortens the heart rate-corrected QT interval (QTc) via direct electrophysiological effects on cardiomyocytes. Moreover, several studies demonstrated important interplays between inflammation and reduced gonad function in men. We hypothesized that, during inflammatory activation in men, testosterone levels decrease and that this enhances TdP risk by contributing to the overall prolonging effect of inflammation on QTc. Methods and Results We investigated (1) the levels of sex hormones and their relationship with inflammatory markers and QTc in male patients with different types of inflammatory diseases, during active phase and recovery; and (2) the association between inflammatory markers and sex hormones in a cohort of male patients who developed extreme QTc prolongation and TdP, consecutively collected over 10 years. In men with active inflammatory diseases, testosterone levels were significantly reduced, but promptly normalized in association with the decrease in C-reactive protein and interleukin-6 levels. Reduction of testosterone levels, which also inversely correlated with 17-beta estradiol over time, significantly contributed to inflammation-induced QTc prolongation. In men with TdP, both active systemic inflammation and hypogonadism were frequently present, with significant correlations between C-reactive protein, testosterone, and 17-beta estradiol levels; in these patients, increased C-reactive protein and reduced testosterone were associated with a worse short-term outcome of the arrhythmia. Conclusions During systemic inflammatory activation, interleukin-6 elevation is associated with reduced testosterone levels in males, possibly deriving from an enhanced androgen-to-estrogen conversion. While transient, inflammatory hypotestosteronemia is significantly associated with an increased long-QT syndrome/TdP risk in men

Non-Invasive Imaging Including Line-Field Confocal Optical Coherence Tomography (LC-OCT) for Diagnosis of Cutaneous Lymphomas

Primary cutaneous lymphomas (PCL) are a heterogeneous group of non-Hodgkin lymphomas arising from malignant T (CTCL) or B (CBCL) cells, often mimicking other skin conditions. Recently, non-invasive diagnostic imaging modalities, including dermoscopy, Reflectance Confocal Microscopy (RCM), and Line-field Optical Coherence Tomography (LC-OCT), have become increasingly important, supporting clinicians in clinical practice. Hence, our study aimed to describe dermoscopic, RCM, and LC-OCT features of PCL and to explore their role in PCL management. Methods: Between December 2022 and January 2024, 40 lesions of 25 patients with PCL were retrospectively analyzed at the Dermatologic Unit of the University of Siena, Italy. Predefined dermoscopic, LC-OCT, and RCM criteria were assessed and their frequencies were calculated. Results: At dermoscopy, CTCL lesions were characterized by pinkish structureless areas (58,6%) and homogeneous distributed dotted vessels (35,7%), whereas 57.1% of CBCL presented with orange-yellow structureless areas. Considering CTCL, lymphocytes in the epidermis, dermal-epidermal junction, and dermis were detected by LC-OCT in 73.1%, 66.7%, and 51.9% and by RCM in 72.2%, 55.6%, and 61.1% of cases, respectively. The detection of lymphocytes was more precise using RCM than LC-OCT in CTCL (p &lt; 0.001). Dermal infiltration of medium-reflective cells was visible in 80% and 40% of CBCL cases by LC-OCT and RCM, respectively. Conclusions: Non-invasive imaging techniques may support clinicians in managing PCL; however, further studies are mandatory in this field

Baricitinib retention rate: ‘real-life’ data from a mono-centric cohort of patients affected by rheumatoid arthritis

ObjectivesThe aim of this retrospective study was to evaluate baricitinib retention rate in patients affected by rheumatoid arthritis. Secondary aims were to compare the impact on treatment persistence of monotherapy and other variables such as systemic corticosteroid use, line of treatment, disease duration, sex, biomarkers positivity, and Herpes Zoster virus infection.Materials and methodsPatients with Rheumatoid Arthritis undergoing baricitinib were consecutively enrolled. Rheumatoid Arthritis diagnosis was performed with 2010 ACR/EULAR classification criteria. The cohort’s demographic, clinical and therapeutical data were retrospectively collected. The whole follow-up duration was 104 weeks.ResultsNinety-five patients affected by rheumatoid arthritis and treated with baricitinib were consecutively enrolled. At the end of follow-up, the overall retention rate was 69.3%. No statistically significant difference in retention rate was observed between patients treated with baricitinib in monotherapy or in combination with methotrexate (p = 0.638) while patients undergoing a steroidal treatment showed a significantly reduced treatment retention (p = 0.028). Contrarily, patients treated with baricitinib as a first-line b/tsDMARD showed higher drug retention (p = 0.002) compared to further treatment lines. Steroid employment, steroid dosage and previous treatment with bDMARDs correlated with risk of treatment discontinuation and at univariate analysis (p = 0.028, p &lt; 0.001, and p = 0.002 respectively). Multivariate analysis confirmed significance for higher steroid dosage and previous treatment with bDMARDs (p = 0.002 and p = 0.046). No adverse events such as deep venous thrombosis, pulmonary embolism or tubercular infection/reactivation were reported during the study observation.ConclusionOur data show a good baricitinib retention rate after 12 and 24 months of observation (75.1 and 69.3%, respectively). In our cohort, concomitant treatment with methotrexate did not influence treatment persistence while retention was reduced in patients undergoing a steroidal treatment and/or in multi-failure subjects

Elevated Interleukin-6 Levels Are Associated With an Increased Risk of QTc Interval Prolongation in a Large Cohort of US Veterans

Background: Although accumulating data indicate that IL-6 (interleukin-6) can promote heart rate-corrected QT interval (QTc) prolongation via direct and indirect effects on cardiac electrophysiology, current evidence comes from basic investigations and small clinical studies only. Therefore, IL-6 is still largely ignored in the clinical management of long-QT syndrome and related arrhythmias. The aim of this study was to estimate the risk of QTc prolongation associated with elevated IL-6 levels in a large population of unselected subjects. Methods and results: An observational study using the Veterans Affairs Informatics and Computing Infrastructure was performed. Participants were US veterans who had an ECG and were tested for IL-6. Descriptive statistics and univariate and multivariate regression analyses were performed to study the relationship between IL-6 and QTc prolongation risk. Study population comprised 1085 individuals, 306 showing normal (&lt;5 pg/mL), 376 moderately high (5-25 pg/mL), and 403 high (&gt;25 pg/mL) IL-6 levels. Subjects with elevated IL-6 showed a concentration-dependent increase in the prevalence of QTc prolongation, and those presenting with QTc prolongation exhibited higher circulating IL-6 levels. Stepwise multivariate regression analyses demonstrated that increased IL-6 level was significantly associated with a risk of QTc prolongation up to 2 times the odds of the reference category of QTc (e.g. QTc &gt;470 ms men/480 ms women ms: odds ratio, 2.28 [95% CI, 1.12-4.50] for IL-6 &gt;25 pg/mL) regardless of the underlying cause. Specifically, the mean QTc increase observed in the presence of elevated IL-6 was quantitatively comparable (IL-6 &gt;25 pg/mL:+6.7 ms) to that of major recognized QT-prolonging risk factors, such as hypokalemia and history of myocardial infarction. Conclusions: Our data provide evidence that a high circulating IL-6 level is a robust risk factor for QTc prolongation in a large cohort of US veterans, supporting a potentially important arrhythmogenic role for this cytokine in the general population

Position statement of the EADV Artificial Intelligence (AI) Task Force on AI‐assisted smartphone apps and web‐based services for skin disease

Background: As the use of smartphones continues to surge globally, mobile applications (apps) have become a powerful tool for healthcare engagement. Prominent among these are dermatology apps powered by Artificial Intelligence (AI), which provide immediate diagnostic guidance and educational resources for skin diseases, including skin cancer. Objective: This article, authored by the EADV AI Task Force, seeks to offer insights and recommendations for the present and future deployment of AI‐assisted smartphone applications (apps) and web‐based services for skin diseases with emphasis on skin cancer detection.MethodsAn initial position statement was drafted on a comprehensive literature review, which was subsequently refined through two rounds of digital discussions and meticulous feedback by the EADV AI Task Force, ensuring its accuracy, clarity and relevance. Results: Eight key considerations were identified, including risks associated with inaccuracy and improper user education, a decline in professional skills, the influence of non‐medical commercial interests, data security, direct and indirect costs, regulatory approval and the necessity of multidisciplinary implementation. Following these considerations, three main recommendations were formulated: (1) to ensure user trust, app developers should prioritize transparency in data quality, accuracy, intended use, privacy and costs; (2) Apps and web‐based services should ensure a uniform user experience for diverse groups of patients; (3) European authorities should adopt a rigorous and consistent regulatory framework for dermatology apps to ensure their safety and accuracy for users. Conclusions: The utilisation of AI‐assisted smartphone apps and web‐based services in diagnosing and treating skin diseases has the potential to greatly benefit patients in their dermatology journeys. By prioritising innovation, fostering collaboration and implementing effective regulations, we can ensure the successful integration of these apps into clinical practice