Prediction of melanoma Breslow thickness using deep transfer learning algorithms.

BACKGROUND: The distinction between in situ melanoma (MIS) and invasive melanoma is challenging even for expert dermatologists. The use of pretrained convolutional neural networks (CNNs) as ancillary decision systems needs further research. AIM: To develop, validate and compare three deep transfer learning (DTL) algorithms to predict MIS vs. invasive melanoma and melanoma with a Breslow thickness (BT) of < 0.8 mm vs. ≥ 0.8 mm. METHODS: A dataset of 1315 dermoscopic images of histopathologically confirmed melanomas was created from Virgen del Rocio University Hospital and open repositories of the International Skin Imaging Collaboration archive and Polesie S et al. (Dermatol Pract Concept 2021; 11:e2021079). The images were labelled as MIS or invasive melanoma and < 0.8 mm or ≥ 0.8 mm of BT. We conducted three trainings, and overall means for receiver operating characteristic (ROC) curves, sensitivity, specificity, positive and negative predictive value, and balanced diagnostic accuracy outcomes were evaluated on the test set with ResNetV2, EfficientNetB6 and InceptionV3. The results of 10 dermatologists were compared with the algorithms. Grad-CAM gradient maps were generated, highlighting relevant areas considered by the CNNs within the images. RESULTS: EfficientNetB6 achieved the highest diagnostic accuracy for the comparison between MIS vs. invasive melanoma (61%) and BT < 0.8 mm vs. ≥ 0.8 mm (75%). For the BT comparison, ResNetV2 with an area under the ROC curve of 0.76 and InceptionV3 with an area under the ROC curve of 0.75, outperformed the results obtained by the dermatologist group with an area under the ROC curve of 0.70. CONCLUSION: EfficientNetB6 recorded the best prediction results, outperforming the dermatologists for the comparison of 0.8 mm of BT. DTL could be an ancillary aid to support dermatologists' decisions in the near future.

Systemic sclerosis mortality trends in Spain from 1980 to 2019: age-period-cohort and joinpoint analysis.

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune chronic rheumatic disease with a high mortality rate, which continues to be a challenge for clinicians today. AIM: To assess changes in mortality trends in the Spanish SSc population between 1980 and 2019, taking into account the independent effects of sex, age, time period and birth cohort. METHODS: SSc death records and mid-year population data were collected from the National Statistics Institute. Age-standardized mortality rates were calculated for the overall population and for each sex (male, female) and age group (5-year groups). Significant changes in mortality trends were identified by joinpoint regressions. An age-period-cohort (APC) analysis and potential years of life lost (PYLL) analysis were performed to identify the burden of SSc. RESULTS: Age-standardized mortality rates due to SSc increased from 1.87 (95% CI 1.00-3.02) per 1 000 000 inhabitants between 1980 and 1984, to 2.47 (95% CI 1.74-3.02) per 1 000 000 inhabitants between 2015 and 2019. The relative risk of mortality fell in all groups in cohorts born after 1990. The PYLL rates showed a gradual rise for both sexes. CONCLUSION: There was an increase in overall SSc mortality in Spain during the 39 years evaluated, although there was a progressive drop for men.

Dropout Rate in Digital Health Interventions for the Prevention of Skin Cancer: Systematic Review, Meta-analysis, and Metaregression.

BACKGROUND: Digital strategies are innovative approaches to the prevention of skin cancer, but the attrition following this kind of intervention needs to be analyzed. OBJECTIVE: The aim of this paper is to assess the dropouts from studies focused on digital strategies for the prevention of skin cancer. METHODS: We conducted this systematic review with meta-analyses and metaregression according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statements. Search terms for skin cancer, digital strategies, and prevention were combined to search PubMed, Scopus, Web of Science, CINAHL, and Cochrane Library from inception until July 2022. Randomized clinical trials that reported dropouts of participants and compared digital strategies with other interventions to prevent skin cancer in healthy or disease-free participants were included. Two independent reviewers extracted data for analysis. The Revised Cochrane Collaboration Bias tool was employed. We calculated the pooled dropout rate of participants through a meta-analysis of proportions and examined whether dropout was more or less frequent in digital interventions against comparators via an odds ratio (OR) meta-analysis. Data were pooled using a random-effects model. Subgroup meta-analyses were conducted in a meta-analysis of proportions and OR meta-analysis to assess the dropout events when data were sorted by digital interventions or control comparator. A univariate metaregression based on a random-effects model assessed possible moderators of dropout. Participants' dropout rates as pooled proportions were calculated for all groups combined, and the digital and comparator groups separately. OR>1 indicated higher dropouts for digital-based interventions. Metaregressions were performed for age, sex, length of intervention, and sample size. RESULTS: A total of 17 studies were included. The overall pooled dropout rate was 9.5% (95% CI 5.0-17.5). The subgroup meta-analysis of proportions revealed a dropout rate of 11.6% for digital strategies (95% CI 6.8-19.0) and 10.0% for comparators (95% CI 5.5-17.7). A trend of higher dropout rates for digital strategies was observed in the overall (OR 1.16, 95% CI 0.98-1.36) and subgroup OR meta-analysis, but no significant differences were found between the groups. None of the covariates moderated the effect size in the univariate metaregression. CONCLUSIONS: Digital strategies had a higher dropout rate compared to other prevention interventions, but the difference was not significant. Standardization is needed regarding reporting the number of and reasons for dropouts. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) CRD42022329669; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=329669.

Hidradenitis suppurativa and Down syndrome in a single-centre sample: A cross-sectional study.

Down syndrome (DS) has been related to a higher risk of hidradenitis suppurativa (HS). This cross-sectional study assessed DS patients with HS in a Spanish single-centre sample. DS participants presented a lower age of onset, age at diagnosis and time to diagnosis. Also, DS was not associated with the severity of HS measured by baseline IHS4 .

Cutaneous malignant melanoma mortality in Andalusia from 1979 to 2018. Toward new perspectives?

Malignant melanoma accounts for 80% of deaths due to skin cancer. Its incidence is globally increasing. However, melanoma mortality seems to be decreasing. The aim of this study was to analyze mortality rates due to melanoma in Andalusia between 1979 and 2018. Deaths due to melanoma and mid-year population in Andalusia were collected from the National Institute of Statistics. Age-adjusted mortality rates were calculated for overall population and for each sex and age group. Regression models were used to calculate significant points of change. Sex ratio and the independent effects of age, period, and cohort were also analyzed. Age-adjusted mortality due to melanoma rose from 0.61 to 1.94 deaths per 100.000 from 1979 to 2018 for the overall population. A significant change of trends was detected around 1994 when, after a steady rise from 1979, mortality rates stabilized up to the end of the period studied. The cited increase was more pronounced in >64 year males. From the end of the 2000s, there was a decrease in mortality rates to date in all population groups, producing a period effect. A stabilization in melanoma mortality rates was observed in Andalusia from 1994 with a decrease in some groups at the beginning of the 21st century. Trends observed in Andalusia do not differ substantially from those in Spain. The development of new therapies and an earlier diagnosis may have an influence in those changes. Studies that compare differences between Spanish regions are needed to define better prevention strategies.

Trends in mortality from lupus in Spain from 1980 to 2018.

BACKGROUND: Recent studies suggest that Systemic lupus erythematosus (SLE) mortality rates in Spain are decreasing. However, SLE mortality in Spain has been poorly studied. The purpose of study is to assess the temporal trends of mortality rates in the Spanish population with SLE from 1980 to 2018. METHODS: Death records and mid-year population data were collected from the National Statistics Institute. Age-standardized mortality rates were calculated for overall population and for each sex and age group. Significant changes in mortality trends were identified by Joinpoint regressions. Also, an Age-period-cohort (APC) and Potential Years of Life Lost (PYLL) analysis was carried out to know the burden of SLE disease. RESULTS: The overall SLE mortality rates in Spain has experimented an increased through the last 39 years. Mortality rates from the period 1980-1984 was 0.83 per 1.000.000 inhabitants, reaching the value to 1.77 cases per 1.000.000 from the period 2014-2018. A decreasing trend has been observed since 1999. CONCLUSIONS: SLE mortality rate has increased in Spain between 1980 and 1999, with a sustained decrease up to our days.

Oral Nadolol for Children with Infantile Hemangiomas and Sleep Disturbances with Oral Propranolol.

BACKGROUND/OBJECTIVE: Oral propranolol has been shown to be safe and effective in infants with infantile hemangioma (IH). Side effects such as sleep disturbances have been associated with propranolol. The aim of this study was to evaluate the efficacy and safety of oral nadolol in a small series of patients whose propranolol therapy was discontinued due to sleep disturbances. METHODS: A retrospective study of patients with IHs who were treated with oral nadolol due to propranolol-related sleep disturbances at a pediatric tertiary care center between July 2008 and March 2013. Clinical response to oral nadolol and disappearance of propranolol-related side effects were analyzed. RESULTS: A total of 97 patients presenting IH received oral propranolol. Nine patients (9.3%) developed sleep disturbances. Oral propranolol was discontinued in seven patients and switched to oral nadolol, with resolution of these side effects in 5 (71%) of the cases. One patient developed sleep disturbances again after four months of oral nadolol. LIMITATIONS: The sample size was too small to draw generalizable conclusions and to draw any statistical inference as to the incidence of sleep disturbances with nadolol therapy. CONCLUSIONS: The use of oral nadolol in the treatment of IH in our series of 7 patients, resolved the propranolol-related sleep disturbances in 5 (71%), while in one patient the symptoms recurred after 4 months of oral nadolol at a dose of 2 mg/kg/day. In most cases, switching beta-blockers did not compromise efficacy, and is recommended when sleep disturbance necessitates discontinuation of beta-blocker therapy of IH.

Melanoma Breslow Thickness Classification using Ensemble-based Knowledge Distillation with Semi-supervised Convolutional Neural Networks.

Melanoma is considered a global public health challenge and is responsible for more than 90% deaths related to skin cancer. Although the diagnosis of early melanoma is the main goal of dermoscopy, the discrimination between dermoscopic images of in situ and invasive melanomas can be a difficult task even for experienced dermatologists. Recent advances in artificial intelligence in the field of medical image analysis show that its application to dermoscopy with the aim of supporting and providing a second opinion to the medical expert could be of great interest. In this work, four datasets from different sources were used to train and evaluate deep learning models on in situ versus invasive melanoma classification and on Breslow thickness prediction. Supervised learning and semi-supervised learning using a multi-teacher ensemble knowledge distillation approach were considered and evaluated using a stratified 5-fold cross-validation scheme. The best models achieved AUCs of 0.6186 ±0.0410 and of 0.7501 ±0.0674 on the former and latter classification tasks, respectively. The best results were obtained using semi-supervised learning, with the best model achieving 0.7751 and 0.8164 AUC, respectively. The results obtained show that semi-supervised learning could improve the performance of trained models in different melanoma classification tasks compared to supervised learning. Automatic deep learning-based diagnosis systems could support medical professionals in their decision, serving as a second opinion or as a triage tool for medical centers.

Primary cutaneous cryptococcosis of the penis.

Primary cutaneous cryptococcosis is characterized by skin lesions confined to one body region, without evidence of simultaneous dissemination. Skin lesions frequently occur in immunocompromised patients. We report a case of primary cutaneous cryptococcosis in an immunocompetent patient affecting genital area successfully treated with oral itraconazole.

Novel Non-Invasive Quantification and Imaging of Eumelanin and DHICA Subunit in Skin Lesions by Raman Spectroscopy and MCR Algorithm: Improving Dysplastic Nevi Diagnosis.

Malignant melanoma (MM) is the most aggressive form of skin cancer, and around 30% of them may develop from pre-existing dysplastic nevi (DN). Diagnosis of DN is a relevant clinical challenge, as these are intermediate lesions between benign and malignant tumors, and, up to date, few studies have focused on their diagnosis. In this study, the accuracy of Raman spectroscopy (RS) is assessed, together with multivariate analysis (MA), to classify 44 biopsies of MM, DN and compound nevus (CN) tumors. For this, we implement a novel methodology to non-invasively quantify and localize the eumelanin pigment, considered as a tumoral biomarker, by means of RS imaging coupled with the Multivariate Curve Resolution-Alternative Least Squares (MCR-ALS) algorithm. This represents a step forward with respect to the currently established technique for melanin analysis, High-Performance Liquid Chromatography (HPLC), which is invasive and cannot provide information about the spatial distribution of molecules. For the first time, we show that the 5, 6-dihydroxyindole (DHI) to 5,6-dihydroxyindole-2-carboxylic acid (DHICA) ratio is higher in DN than in MM and CN lesions. These differences in chemical composition are used by the Partial Least Squares-Discriminant Analysis (PLS-DA) algorithm to identify DN lesions in an efficient, non-invasive, fast, objective and cost-effective method, with sensitivity and specificity of 100% and 94.1%, respectively.

Non-Melanoma Skin Cancer Mortality in Spain: A Predictive Model up to 2044.

Non-melanoma skin cancers (NMSC) are the most common malignancies worldwide and are, worryingly, increasing in incidence. However, data in the literature on NMSC specific mortality are scarce, because these tumors are excluded from most mortality registries. The main objective of this study is to analyze NMSC's mortality rates and use them to generate a predictive model for the coming years in Spain. Data on mid-year population and death certificates for the period 1979-2019 were obtained from the Spanish National Statistics Institute. The Nordpred program (Cancer Registry of Norway, Oslo, Norway) within statistical program R was used to calculate mortality adjusted rates, as well as the mortality projection with an age-period-cohort model. This is the first study to report a prediction about NMSC mortality in the next years. According to our findings, the number of NMSC deaths in older people will grow in both sexes, especially in those older than >85 years old (y.o.). The age-specific mortality rates of NMSC will tend to stabilize or gradually decrease, with the exception of women between 75-79 y.o., who will present a slight increase at the end of the period. Early prevention and screening of NMSC specifically oriented to this population might change this tendency.

Primary cutaneous carcinosarcoma: clinical, histological, and immunohistochemical analysis of eight cases.

BACKGROUND: Cutaneous carcinosarcoma is a rare biphasic tumor comprising malignant epithelial and heterologous mesenchymal elements. Data on the clinical and histopathologic characteristics of this tumor are scarce. The objective of this study was to describe the clinicopathologic and immunohistochemical features of cutaneous carcinosarcoma. METHODS: A descriptive retrospective study was conducted in a tertiary care hospital from Spain. We reviewed the records of eight patients with cutaneous carcinosarcoma who were diagnosed from 2009 to 2019. RESULTS: The mean patient age at diagnosis was 72.13 years (range 44-91 years), and there was a male predilection (6 cases). The most common site of cutaneous carcinosarcoma was the head and neck (5 cases). Carcinosarcomas demonstrated variable histopathological and immunohistochemical features. Follow-up was available for 7-8 patients. There were two cases of local recurrence and one case of metastasis. Two patients died from the tumor during the entire follow-up. CONCLUSIONS: Although the number of cases in this study was limited, our results provide valuable insight into the clinical, histopathologic, and immunohistochemical characteristics of primary cutaneous carcinosarcoma.

Mortality associated with non-melanoma skin cancer in Spain from 1979 to 2018: trends and age-adjusted rates.

Non-melanoma skin cancers (NMSCs) are the most frequent group of malignant tumours worldwide. Objectives: The aim of the present research was to analyse mortality associated with NMSC in Spain between 1979 and 2018 and highlight changes regarding trend in mortality and differences according to age groups and gender. Death records and mid-year population data were collected from the National Statistics Institute. Age-standardized mortality rates were calculated. Significant changes in mortality trends were identified using Joinpoint regression. The independent effects of age, period and cohort and potential years of life lost due to NMSC were also analysed. Mortality rates associated with NMSC in Spain were reported as 2.49 per 100,000 inhabitants in 1979 (95% CI: 2.24-2.77) and 1.27 per 100,000 inhabitants in 2018 (95% CI; 1.16-1.39) for the overall population. Women who were born after the 70 s showed a significant increase in relative risk of death due to NMSC. Mortality associated with NMSC in Spain shows a decreasing overall trend that appears to have stabilized since 2005, with the exception of women between 35 and 64 years old.

Two cases of cutaneous chronic graft versus host disease in treatment with psoralen plus ultraviolet-A-bath photochemotherapy.

BACKGROUND: Up to 50% of patients undergoing allogenic stem cell transplantation or bone marrow transplantation (BMT) can develop acute or chronic graft versus host disease (GVHD) as a severe complication. Immunosuppressive therapies may prove not only ineffective but may cause serious adverse effects. GVHD remains a major clinical problem and is often associated with high mortality rates. METHODS: This article presents the cases of a 48-year-old woman and a 23-year-old man, both presenting with severe cutaneous sclerodermic chronic GVHD following allogenic stem cell transplantation. Despite several years of treatment with oral corticosteroids, mycophenolate mofetil, sirolimus and acitretine, the skin lesions had not improved. Both patients were then treated with psoralen plus ultraviolet (PUVA)-bath photochemotherapy three times weekly, following a standardized treatment protocol. RESULTS: After a total accumulated dose of about 90 J/cm2, skin lesions in both patients had improved, showing complete remission in some body areas. Systemic corticosteroid treatment could be gradually reduced in the case of the female patient and skin conditions remained stable during maintenance treatment of PUVA-bath two times weekly and during a mean follow-up period of eight months. CONCLUSION: Oral PUVA therapy has been established as a successful treatment for acute and chronic GVHD, but unfortunately may result in systemic side effects. Psoralen plus ultraviolet-A-bath photochemotherapy provides clinicians with a therapeutic alternative that offers high clinical efficacy and safety. Therefore, PUVA-bath could be included as an alternative in the treatment protocol for chronic cutaneous GVHD.

Expression Pattern of Aquaporin 1 and Aquaporin 3 in Melanocytic and Nonmelanocytic Skin Tumors.

OBJECTIVES: Study of aquaporin 1 (AQP1) and aquaporin 3 (AQP3) expression to understand its potential role in the pathophysiology of skin cancer. METHODS: Analysis of AQP1 and AQP3 expression by immunohistochemistry of 72 skin biopsy specimens from melanocytic skin tumors, nonmelanocytic tumors, or healthy samples. RESULTS: AQP1 showed strong labeling in 100% of benign common melanocytic nevi. Small blood vessels, stroma, and melanophages surrounding different types of melanomas tumors also were positive. Tumoral melanocytes in atypical nevi and melanomas were negative for AQP1. AQP3 showed strong labeling in 100% of melanocytic nevi, 100% of atypical melanocytic nevi, and 100% of melanomas. In all basal cell carcinomas and squamous cell carcinomas, staining for AQP3 was positive. CONCLUSIONS: To our knowledge, this work represents the first demonstration of AQP1/AQP3 expression in human melanocytic skin tumors. More studies are needed to understand the underlying molecular mechanisms of expression of both AQPs in melanocytic tumors and their potential as molecular therapeutic targets.

Effect of age, birth cohort and period of death on skin melanoma mortality in Spain, 1975 through 2004.

Recent statistics cohort analysis of mortality reveals that skin melanoma rates are dropping in the younger cohorts. Therefore, the aim of this study is to provide up-to-date information and to analyze recent changes in skin melanoma mortality trends in Spain during the period of 1975-2004 using joinpoint regression and age-period-cohort models. Between 1975 and 2004, the age-standardized (overall) mortality rates for skin melanoma increased from 0.3 to 1.3 per 100,000 person-years for males and from 0.2 to 0.8 per 100,000 person-years for females, with an estimated annual percentage of change of 4.8 and 4.3%, respectively. In men and women, the best fit was found for the full model, which simultaneously considered the effects of age, period and cohort. The risks among both males and females increased in each successive birth cohort born between 1895 and 1950. Thereafter, the risks declined through the most recent birth cohort born in 1970. Examination of the mortality trends by age group and birth cohort revealed that the recent less rapidly rising (men) or stabilizing (women) age-adjusted skin melanoma mortality rates in Spain were a result of declining mortality in the younger age groups and more recent birth cohorts. The particularly favorable trends in young people suggest that a further decline in mortality from skin melanoma in Spain is likely to occur within the next few years.