A re-assessment of the value of markers of corticosteroid contact allergy in the Spanish baseline series: Clobetasol propionate in the spotlight.

BACKGROUND: Budesonide and tixocortol pivalate as markers of contact allergy to corticosteroids have been questioned, as they are not able to detect a significant percentage of allergic patients. OBJECTIVES: To investigate the potential role of clobetasol propionate in enhancing corticosteroid sensitisation detection. METHODS: Between January 2022 and December 2023, patients who attended centres involved in the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy were tested with an extended baseline series that included budesonide, tixocortol pivalate, clobetasol propionate 0.1% in ethanol and 1% in petrolatum. RESULTS: A total of 4338 patients were tested. Twenty-four patients were allergic to budesonide (0.55%, 95% CI: 0.37-0.82); nine patients were allergic to tixocortol pivalate (0.21%, 95% CI: 0.11-0.39); and 23 patients were allergic to clobetasol (0.53%, 95% CI: 0.35-0.79). Only four of those patients allergic to clobetasol were detected by budesonide and one by tixocortol pivalate. No significant differences in the number of positive tests were found between clobetasol in petrolatum or ethanol. CONCLUSIONS: In Spain budesonide remains the main corticosteroid allergy marker whereas the role of tixocortol pivalate is questionable. The addition of clobetasol propionate to the Spanish baseline series would improve the ability to detect patients allergic to corticosteroids.

AI-Dentify: deep learning for proximal caries detection on bitewing x-ray - HUNT4 Oral Health Study.

BACKGROUND: Dental caries diagnosis requires the manual inspection of diagnostic bitewing images of the patient, followed by a visual inspection and probing of the identified dental pieces with potential lesions. Yet the use of artificial intelligence, and in particular deep-learning, has the potential to aid in the diagnosis by providing a quick and informative analysis of the bitewing images. METHODS: A dataset of 13,887 bitewings from the HUNT4 Oral Health Study were annotated individually by six different experts, and used to train three different object detection deep-learning architectures: RetinaNet (ResNet50), YOLOv5 (M size), and EfficientDet (D0 and D1 sizes). A consensus dataset of 197 images, annotated jointly by the same six dental clinicians, was used for evaluation. A five-fold cross validation scheme was used to evaluate the performance of the AI models. RESULTS: The trained models show an increase in average precision and F1-score, and decrease of false negative rate, with respect to the dental clinicians. When compared against the dental clinicians, the YOLOv5 model shows the largest improvement, reporting 0.647 mean average precision, 0.548 mean F1-score, and 0.149 mean false negative rate. Whereas the best annotators on each of these metrics reported 0.299, 0.495, and 0.164 respectively. CONCLUSION: Deep-learning models have shown the potential to assist dental professionals in the diagnosis of caries. Yet, the task remains challenging due to the artifacts natural to the bitewing images.

Treatment of severe atopic dermatitis with tralokinumab in clinical practice: short-term effectiveness and safety results.

BACKGROUND: Tralokinumab was recently approved for the treatment of moderate-to-severe atopic dermatitis (AD) and is the first selective interleukin (IL)-13 inhibitor that specifically neutralizes IL-13 with high affinity. OBJECTIVES: To determine the real-life short-term effectiveness and safety of tralokinumab treatment in patients with moderate-to-severe AD. METHODS: A multicentre retrospective study was conducted including adult patients with moderate-to-severe AD who started tralokinumab treatment from 1 April to 30 June 2022 in 16 Spanish hospitals. Demographic and disease characteristics, severity and quality of life scales were collected at the baseline visit and at weeks 4 and 16. RESULTS: Eighty-five patients were included. Twenty-seven patients (32%) were non-naive to advanced therapy (biological or Janus kinase inhibitors inhibitors). All included patients had severe disease with baseline Eczema Area and Severity Index (EASI) scores of 25.4 (SD 8.1), Dermatology Life Quality Index (DLQI) 15.8 (5.4) and peak pruritus numerical rating scale (PP-NRS) 8.1 (1.8) and 65% had an Investigator's Global Assessment (IGA) of 4. At week 16, there was improvement on all scales. The mean EASI decreased to 7.5 (SD 6.9, 70% improvement), SCORing Atopic Dermatitis improved 64% and PP-NRS, 57%. Also, 82%, 58% and 21% of the patients achieved EASI 50, 75 and 90, respectively. The percentage of EASI 75 responders was significantly higher among the naive vs. non-naive groups (67% vs. 41%). The safety profile was acceptable. CONCLUSIONS: Patients, with a long history of disease and prior multidrug failure, showed a good response to tralokinumab, confirming clinical trial results.

Frequency of sensitization to the individual fragrances of fragrance mix I and II according to the factors included in the MOAHLFA index.

BACKGROUND: Fragrances constitute the second most frequent cause of allergic contact dermatitis in Spain. OBJECTIVES: To determine the rate of sensitization to the individual fragrances of fragrance mix (FM) I and FM II for each of the demographic and clinical factors included in the MOAHLFA (male, occupational dermatitis, atopic dermatitis, hand dermatitis, leg dermatitis, facial dermatitis, age) index. METHODS: We conducted a 5-year retrospective study in 23 Spanish centres. We identified the patients who had undergone patch testing with a specific fragrance series after reacting positively to fragrance markers in a baseline series. We obtained the MOAHLFA index items in this population, then calculated for each demographic and clinical factor the frequencies of sensitization to the individual fragrances of FM I and FM II. RESULTS: A specific fragrance series was patch tested in 1013 patients. The most frequent allergens in men, women, children, and retired people were Evernia prunastri (16%), geraniol (16.6%), isoeugenol (17.9%), and geraniol (22.4%), respectively. Citral (20.5%) and hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) (14.5%) were the most common allergens in occupational eczemas and were also associated with a large proportion of hand and facial dermatitis. CONCLUSIONS: Frequency of sensitization to the individual fragrances of FM I and FM II varies with age, sex, affected body region, and history of occupational or atopic dermatitis.

Influence of sampling accuracy on augmented reality for laparoscopic image-guided surgery.

PURPOSE: This study aims to evaluate the accuracy of point-based registration (PBR) when used for augmented reality (AR) in laparoscopic liver resection surgery. MATERIAL AND METHODS: The study was conducted in three different scenarios in which the accuracy of sampling targets for PBR decreases: using an assessment phantom with machined divot holes, a patient-specific liver phantom with markers visible in computed tomography (CT) scans and in vivo, relying on the surgeon's anatomical understanding to perform annotations. Target registration error (TRE) and fiducial registration error (FRE) were computed using five randomly selected positions for image-to-patient registration. RESULTS: AR with intra-operative CT scanning showed a mean TRE of 6.9 mm for the machined phantom, 7.9 mm for the patient-specific phantom and 13.4 mm in the in vivo study. CONCLUSIONS: AR showed an increase in both TRE and FRE throughout the experimental studies, proving that AR is not robust to the sampling accuracy of the targets used to compute image-to-patient registration. Moreover, an influence of the size of the volume to be register was observed. Hence, it is advisable to reduce both errors due to annotations and the size of registration volumes, which can cause large errors in AR systems.

Psychometric properties of the Spanish version of the once-daily Urticaria Activity Score (UAS) in patients with chronic spontaneous urticaria managed in clinical practice (the EVALUAS study).

BACKGROUND: The daily diary Urticaria Activity Score (UAS) and its weekly score (UAS7) are widely used to assess signs and symptoms in patients with chronic spontaneous urticaria (CSU). The objective of this study was to assess the psychometric properties of a Spanish version of the once-daily UAS. METHODS: Observational study in patients ≥18 years old receiving usual care for CSU (daily or almost daily occurrence of generalized hives or angioedema for ≥6 weeks). Patients were included consecutively and completed the UAS, EQ-5D, and the Chronic Urticaria Quality of Life scale (CU-Q2oL) at two study visits 6 weeks apart. On each occasion, the UAS was completed once-daily for 7 consecutive days to be able to calculate the UAS7 score. Psychometric properties of reliability, construct validity, and responsiveness were assessed. The Minimal Important Difference (MID) was estimated for the UAS7 using anchor- and distribution-based approaches. RESULTS: Data from 166 patients was available for analysis (mean age 49 years, 65.7% female). Floor (5.4% of patients with the lowest possible score) and ceiling (1.2%) effects were low; 15% of patients had missing values. Internal consistency and test-retest reliability were good (Cronbach's alpha of 0.83 and an ICC of 0.84, respectively). Convergent validity was demonstrated through the pattern of correlations with the EQ-5D and CU-Q2oL and known groups' validity was demonstrated by the instrument's ability to discriminate between patients with different overall levels of urticaria severity, with between-group effect-sizes (ES) ranging from 0.36 to 1.19. The UAS7 proved responsive to change with effect sizes ranging from 0.3 to 1.52 in patients reporting improvement or deterioration in overall urticaria status. The MID for the UAS7 score was estimated at 7-8 points, on a scale of 0-42. CONCLUSIONS: The Spanish version of the UAS score has demonstrated a robust psychometric performance in patients with CSU managed in conditions of usual care. It can therefore be considered a suitable instrument to assess disease activity in clinical practice in Spanish-speaking patients. The Spanish version's reliability and validity are similar to those reported for other language versions of the once- and twice-daily variants of the UAS.

Sensitization to fragrances in Spain: A 5-year multicentre study (2011-2015).

BACKGROUND: Fragrance chemicals constitute the second most frequent cause of contact allergy in Spain. There are no data available concerning the individual fragrances that are most frequently involved. OBJECTIVES: To describe the diagnostic contribution provided by specific fragrance series to the results obtained with baseline series fragrance markers by correlating the results of both series. MATERIALS AND METHODS: We performed a 5-year retrospective study of fragrance marker-positive patients tested with specific fragrance series in 23 Spanish centres. We collected the demographic and clinical characteristics, and compared the results of patch tests obtained from different suppliers. RESULTS: Of 19 588 patients patch tested with the Spanish baseline series, 1590 (8.1%) reacted positively to a fragrance marker. Of these, 1013 (63.7%) were patch tested with a fragrance series, and 664 patients reacted positively to at least one individual fragrance other than hydroxyisohexyl 3-cyclohexene carboxaldehyde. Geraniol was the most frequent allergen. Positive reactions to substances not included in fragrance mix (FM) I or FM II were found in 230 patients. Of the 436 FM I-positive patients and the 419 FM II-positive patients, 184 (42%) and 64 (39.1%), respectively, had no positive reactions to fragrance series. In the case of FM I, negative results were more common when individual fragrances were patch tested at low concentrations. CONCLUSIONS: We recommend patch testing all patients positive for any fragrance marker with a specific fragrance series. The correlation between the results of baseline series and fragrance series could be improved by increasing the concentrations of individual fragrances.

Micosis fungoide e inhibidores del TNFα: ¿riesgo o beneficio?

The growing use of anti-TNF drugs during the last years has reopened the discussion about the possible increased risk of developing non-Hodgkin lymphoma in patients with such type of treatments. We present our clinical experience and critical opinion about the current situation of such issue regarding cutaneous T-cell lymphomas.El creciente uso de fármacos anti-TNF durante los últimos años ha reabierto el debate sobre el posible aumento de riesgo de linfomas no Hodgkin en los pacientes con este tipo de tratamientos. Presentamos nuestra experiencia clínica y opinión critica sobre la situación actual de este tema en relación a los linfomas cutáneos de células T.

Treatment of atopic dermatitis with abrocitinib in real practice in Spain: efficacy and safety results from a 24-week multicenter study.

BACKGROUND: Abrocitinib, a selective JAK 1 inhibitor, was recently approved in Europe. Despite its approval, real-world data on its efficacy and safety in treating moderate-to-severe atopic dermatitis (AD) remains limited. OBJECTIVES: This study aimed to evaluate the short-term effectiveness and safety of abrocitinib in a real-life setting for patients with moderate-to-severe AD. METHODS: We conducted a retrospective multicenter study involving adult patients with moderate-to-severe AD who started abrocitinib treatment between May 1, 2023, and September 30, 2023, in 15 Spanish hospitals. Treatment doses were 100 or 200 mg daily, based on clinical assessment. Data collection included patient demographics, AD history, comorbidities, previous treatments, and disease severity indicators such as SCORing atopic dermatitis (SCORAD), Eczema Area and Severity Index (EASI), body surface area, and Peak Pruritus NRS scores at baseline, 4, 12, and 24 weeks. Quality of life was measured using the Dermatology Life Quality Index (DLQI), and safety was assessed by monitoring adverse reactions and various biochemical parameters. RESULTS: The cohort comprised 76 patients with an average age of 33.93 years; 57.89% were male. Before abrocitinib, 36.84% were naïve to advanced therapies. The baseline mean scores were SCORAD 47.04, EASI 21.79, and DLQI 15.01. At Week 24, there were significant improvements: EASI was reduced to 2.81, and 70.58% of the patients achieved EASI 75. However, 18.42% discontinued treatment mainly due to inefficacy or adverse effects. The safety profile was favorable, with 22.37% reporting mild adverse events (AEs) and one serious case of cutaneous lymphoma. CONCLUSIONS: This first Spanish series assessing abrocitinib in real-world conditions reveals a significant improvement in AD symptoms and quality of life in a range of severity and prior treatment failures. Abrocitinib was well-tolerated, with few serious AEs, highlighting its potential as an effective treatment option for AD.

Learning deep abdominal CT registration through adaptive loss weighting and synthetic data generation.

PURPOSE: This study aims to explore training strategies to improve convolutional neural network-based image-to-image deformable registration for abdominal imaging. METHODS: Different training strategies, loss functions, and transfer learning schemes were considered. Furthermore, an augmentation layer which generates artificial training image pairs on-the-fly was proposed, in addition to a loss layer that enables dynamic loss weighting. RESULTS: Guiding registration using segmentations in the training step proved beneficial for deep-learning-based image registration. Finetuning the pretrained model from the brain MRI dataset to the abdominal CT dataset further improved performance on the latter application, removing the need for a large dataset to yield satisfactory performance. Dynamic loss weighting also marginally improved performance, all without impacting inference runtime. CONCLUSION: Using simple concepts, we improved the performance of a commonly used deep image registration architecture, VoxelMorph. In future work, our framework, DDMR, should be validated on different datasets to further assess its value.

Deep learning for image-based liver analysis - A comprehensive review focusing on malignant lesions.

Deep learning-based methods, in particular, convolutional neural networks and fully convolutional networks are now widely used in the medical image analysis domain. The scope of this review focuses on the analysis using deep learning of focal liver lesions, with a special interest in hepatocellular carcinoma and metastatic cancer; and structures like the parenchyma or the vascular system. Here, we address several neural network architectures used for analyzing the anatomical structures and lesions in the liver from various imaging modalities such as computed tomography, magnetic resonance imaging and ultrasound. Image analysis tasks like segmentation, object detection and classification for the liver, liver vessels and liver lesions are discussed. Based on the qualitative search, 91 papers were filtered out for the survey, including journal publications and conference proceedings. The papers reviewed in this work are grouped into eight categories based on the methodologies used. By comparing the evaluation metrics, hybrid models performed better for both the liver and the lesion segmentation tasks, ensemble classifiers performed better for the vessel segmentation tasks and combined approach performed better for both the lesion classification and detection tasks. The performance was measured based on the Dice score for the segmentation, and accuracy for the classification and detection tasks, which are the most commonly used metrics.

Comorbidity identification and referral in atopic dermatitis: a consensus document.

BACKGROUND: Atopic dermatitis (AD) is associated with different comorbidities. OBJECTIVE: To develop evidence-based and practical recommendations for comorbidity detection in patients with AD in daily practice. METHODS: We employed a modified RAND/UCLA methodology, including a systematic literature review (SLR). A group of six experts on AD was established. We conducted a comprehensive search strategy on Medline, Embase, and Cochrane Library up to June 2020. The selection criteria included studies with AD patients with any comorbidity reporting data on comorbidity prevalence, burden, and management. The included studies quality was assessed. The SLR results were discussed in a nominal group meeting, and several recommendations were generated. The recommendation agreement grade was tested on additional experts through a Delphi process. RESULTS: The recommendations cover the following issues: (1) Which comorbidities should be investigated at the first and subsequent visits; (2) how and when should comorbidities be investigated (screening); (3) how should patients with specific comorbidities be referred to confirm their diagnosis and initiate management; (4) specific recommendations to ensure an integral care approach for AD patients with any comorbidity. CONCLUSIONS: These recommendations seek to guide dermatologists, patients, and other stakeholders in regard to early comorbidity identification and AD patient referral to improve decision-making.

Topical heparin as an effective and safe treatment for patients with capecitabine-induced hand-foot syndrome: results of a phase IIA trial supported by proteomic profiling of skin biopsies.

Background: Hand-foot syndrome (HFS) is a common adverse reaction associated with capecitabine chemotherapy that significantly affects the quality of life of patients. This study evaluates the safety and effectiveness of a topical heparin (TH) treatment on the clinical manifestations and anatomopathological alterations of capecitabine-induced HFS. In addition, we performed proteome profiling of skin biopsies obtained from patients with HFS at baseline and after heparin treatment. Methods: Patients with grade ⩽ 2 HFS associated with capecitabine were included in this study. The primary end point was the effectiveness of TH in reducing HFS of any grade. Clinical improvement was evaluated by clinicians, and an improvement was perceived by patients who performed a weekly visual analog scale questionnaire. Secondary end points included a comparative histological analysis and protein expression in skin biopsies at baseline and after 3 weeks of HT treatment. Proteomic profiling was carried out using quantitative isobaric labelling and subsequently validated by a T-array. Results: Twenty-one patients were included in the study. The median TH treatment time was 7.6 weeks (range = 3.6-41.6 weeks), and the median response time was 3.01 weeks (95% CI = 2.15-3.97). At the end of treatment, 19 of 21 patients (90.48%) responded to treatment with a decrease in one or more grades of HFS. None of the patients experienced adverse effects related to TH usage, nor did they suspend chemotherapy treatment. The main findings observed in skin biopsies after treatment were a decrease in hyperkeratosis and lymphocytic infiltrates. The proteomic analysis showed altered expression of 34 proteins that were mainly related to wound healing, cell growth, and the immune response. Conclusion: Based on our results, topical heparin is an effective and safe treatment for clinical manifestations of HFS, probably due to the restauration of skin homeostasis after heparin treatment, as supported by our proteomics-derived data. Trial registration: EudraCT 2009-018171-13.

Usefulness of Patch Testing With Patient's Own Products in the Diagnosis of Allergic Contact Dermatitis.

BACKGROUND: The usefulness of using patient's own products in patch tests for the diagnosis of allergic contact eczema is well known. However, most of the literature is based on case series published decades ago, and they are focused on cosmetics and fragrances. OBJECTIVE: The aim of the study was to evaluate the usefulness of using patient's own products in patch tests for the diagnosis of contact eczema in a contact dermatitis unit, describing the most frequently positive own products, as well as the most frequently responsible allergens. METHODS: In a 17-year period, 3514 patients were patch tested in our department. In 2429 patients, patch testing with the patients' own products was performed. RESULTS: We found that 363 patients (10.33%) reacted to their own products. In 131 cases (3.81%), reacting to their own product was the only clue for detecting the responsible allergen for allergic contact eczema. Most reactions were found for topical medications, moisturizers, and adhesives. Fragrance mix I, methylchloroisothiazolinone/methylisothiazolinone, ketoprofen, and colophony were found to be the allergens most often responsible. CONCLUSIONS: It is essential to include patient's own products in the study of allergic contact eczema to make a correct diagnosis. In our series, 3.81% of the patients would not have been correctly diagnosed if their own products had not been included in patch tests.