Different mutational profiles of subcutaneous panniculitis-like T-cell lymphoma and lupus panniculitis: an additional case series.

BACKGROUND AND OBJECTIVE: subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare cytotoxic T-cell lymphoma with indolent behavior, mostly present in women and associated with immunological diseases whose pathogenic background is still poorly understood. SPTCL is associated with lupus erythematosus panniculitis (LEP) and histologically misdiagnosed. OBJECTIVES: the aim of our study was to identify mutations affecting the pathogenesis of both SPTCL and LEP. MATERIALS AND METHODS: we studied a total of 10 SPTCL and 10 LEP patients using targeted Next Generation Sequencing and pyrosequencing. Differences in gene expression between molecular subgroups were investigated using NanoString technology. Clinical data were collected, and correlations sought with the molecular data obtained. RESULTS: the mutational profile of SPTCL and LEP is different. We identified fewer pathogenic mutations than previously reported in SPTCL, noting a single HAVCR2-mutated SPTCL case. Interestingly, 40% of our SPTCL cases showed the pathogenic TP53 (p.Pro72Arg) (P72R) variant. Although cases showing HAVCR2 mutations or the TP53 (P72R) variant had more severe symptomatic disease, none developed hemophagocytic syndrome (HPS). Furthermore, TP53 (P72R)-positive cases were characterized by a lower metabolic signaling pathway and higher levels of CD28 expression and Treg signaling genes. In addition, 30% of our cases featured the same mutation (T735C) of the epigenetic modificatory gene DNMT3A. None of the LEP cases showed mutations in any of the studied genes. CONCLUSIONS: the mutational landscape of SPTCL is broader than previously anticipated. We describe, for the first time, the involvement of the TP53 (P72R) pathogenic variant in this subgroup of tumors, consider the possible role of different genetic backgrounds in the development of SPTCL, and conclude that LEP does not follow the same pathogenic pathway as SPTCL.

Standard and Expanded Series Patch Testing Update by the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC). / Actualización de la batería estándar y batería ampliada de pruebas alérgicas de contacto por el Grupo Español de Investigación en Dermatitis de Contacto y Alergia Cutánea (GEIDAC).

After the meeting held by the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC) back in October 2021, changes were suggested to the Spanish standard series patch testing. Hydroxyethyl methacrylate (2% pet.), textile dye mixt (6.6% pet.), linalool hydroperoxide (1% pet.), and limonene hydroperoxide (0.3% pet.) were, then, added to the series that agreed upon in 2016. Ethyldiamine and phenoxyethanol were excluded. Methyldibromoglutaronitrile, the mixture of sesquiterpene lactones, and hydroxyisohexyl 3-cyclohexene (Lyral) were alo added to the extended Spanish series of 2022.

Epidemiological, Clinical, and Allergic Profile of Psoriatic Patients. Evaluation of the Spanish Registry of Contact Dermatitis and Cutaneous Allergy (REIDAC). / Perfil epidemiológico, clínico y alérgico en pacientes con psoriasis. Evaluación del Registro Español de Dermatitis de Contacto (REIDAC).

BACKGROUND: Psoriasis is a chronic inflammatory dermatosis whose clinical and topographic distribution requires differential diagnosis, or the possible association with allergic contact dermatitis (ACD), requiring patch testing (PT) as part of the diagnostic procedure. OBJECTIVES: To describe the epidemiological, clinical, and allergic profile of patients with a primary or secondary diagnosis of psoriasis undergoing PT and compare them with patients with a diagnosis of ACD at the end of the diagnostic process. METHODS: Cross-sectional study with data from REIDAC from 2018 through 2023 of selected patients with a diagnosis of psoriasis and/or ACD. RESULTS: A total of 11 502 patients were included, 513 of whom had been diagnosed with primary or secondary psoriasis, 3640 with ACD, and 108 with both diseases. Men were more predominant in the groups of patients with psoriasis, psoriasis+ACD, and lesions were more predominantly seen in the hands with little association with atopic factors vs the ACD group. The rate of positivity in PT to the 2022 Spanish battery of allergens was lower in the group with psoriasis only in 27% of the patients. The most common allergens found in the psoriasis group were also the most common ones found in the overall ACD population. CONCLUSIONS: Overall, 36.2% of psoriatic patients tested positive in PT to the 2022 Spanish battery of allergens, which proved that this association is not uncommon. Overall, psoriatic patients had a higher mean age, were more predominantly men, and showed more hand involvement.

Acquired vibratory angioedema with a severe impact on work performance.

Vibratory urticaria/angioedema is an inducible type of urticaria that may be elicited by vibratory stimuli from work tool and instruments. A 39-year-old male construction worker was diagnosed with acquired vibratory angioedema associated with chronic spontaneous urticaria involving a severe work performance impairment. Response to omalizumab was immediate and complete. We evaluated the Urticarial Activity Score; the response to the vibratory angioedema provocation vortex test; and evolution of analytical parameters (e.g. high-affinity IgE receptor expression on peripheral blood basophils, C-reactive protein, D-dimer and IgE levels). Vibratory angioedema may be misdiagnosed as delayed pressure urticaria if the appropriate specific provocation tests are not performed. According to our knowledge, this is the first time a pneumatic hammer is described as a trigger; the first case responding to omalizumab; and the second published case associated with spontaneous chronic urticaria.

Epidemiological, Clinical, and Allergy Profile of Patients With Atopic Dermatitis and Hand Eczema: Evaluation of the Spanish Contact Dermatitis Registry (REIDAC). / Perfil epidemiológico, clínico, y alérgico en pacientes con dermatitis atópica y dermatitis de las manos. Evaluación del Registro Español de Dermatitis de Contacto (REIDAC).

BACKGROUND: Hand eczema is common in patients with atopic dermatitis (AD), but few studies have described the characteristics of these patients in large, representative populations from different geographic regions and occupational settings. OBJECTIVE: To describe the epidemiological, clinical, and allergy profile of patients with hand eczema who underwent patch testing and compare patients with and without AD. METHODS: Analysis of data from the Spanish Contact Dermatitis Registry, a multicenter registry of patients who undergo patch testing in Spain. RESULTS: We included 1466 patients with hand eczema who were patch tested between January 2018 and June 2020. Those with AD were younger and had had symptoms for longer before testing. They were also more likely to have been exposed to occupational triggers (38% vs 53% for patients without AD). The only profession for which significant differences were found was hairdressing. The most common allergens were nickel sulfate, methylchloroisothiazolinone/methylisothiazolinone, cobalt chloride, potassium dichromate, fragrance mixes I and II, and formaldehyde. The most common diagnoses were allergic contact dermatitis (24% vs 31% in patients with and without AD, P=.0224) and irritant contact dermatitis (18% and 35% respectively, P<.001). CONCLUSIONS: AD is common in patients with predominant hand eczema who undergo patch testing. Patients with hand eczema and AD have different clinical and epidemiological characteristics to hand eczema patients in general and their final diagnosis following patch testing is also different.

Patch Testing During the COVID-19 Pandemic: Recommendations of the AEDV's Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC). / Recomendaciones del Grupo Español de Investigación en Dermatitis de Contacto y Alergia Cutánea (GEIDAC) de la AEDV en relación con la realización de pruebas epicutáneas durante la pandemia por SARS-CoV-2 (COVID-19).

As the COVID-19 pandemic gradually comes under control, the members of the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC) have drawn up a proposed list of the requirements, limitations, and conditioning factors affecting the resumption of work in contact dermatitis units. The assumption is that the severe acute respiratory syndrome coronavirus2 is still circulating and that occasional or seasonal outbreaks will occur. They recommend that the first step should be to assess how many patch tests each clinic can handle and review the waiting list to prioritize cases according to disease severity and urgency. Digital technologies can, where possible, be used to send and receive the documentation necessary for the patch test (information, instructions, informed consent, etc.). If the necessary infrastructure is available, patients can be offered the option of a remote initial consultation. Likewise, in selected cases, the patch test results can be read in a virtual visit using photographs taken by the patient or a video visit can be scheduled to allow the physician to evaluate the site of application remotely. These measures will reduce the number of face-to-face visits required, but will not affect the time spent on each case, which must be scheduled in the normal manner. All of these recommendations are suggestions and should be adapted to the needs and possibilities of each health centre.

TRIM72 Immunohistochemical Expression Can Predict Relapse in Colorectal Carcinoma.

Large bowel adenocarcinoma is one of the most frequent human neoplasms and despite recent insights into the pathophysiology and molecular basis of this disease, mortality remains high in advanced and metastatic cases. Most guidelines recommend adjuvant chemotherapy for tumours involving lymph nodes, but not for patients with localized stage I or II disease. However, it is well known that approximately 20% of stage II colorectal carcinoma patients eventually recur, mainly with distant or peritoneal involvement and show bad prognosis. It would be important to predict which patients are at increased risk of recurrence to guide potential adjuvant therapy use in this controversial setting. In this sense, only microsatellite stability has been proposed as a predictive tool in some guidelines. The tripartite motif family protein 72 (TRIM72) is a ubiquitin ligase, involved in the cell membrane repair machinery and known to be associated to insulin resistance. Its potential role in colon cancer has recently been proposed. The aim of this study is to determine the potential predictive value of TRIM72 immunohistochemical expression in stage II colon carcinoma. We have retrospectively reviewed a series of 95 patients with stage II colon microsatellite stable carcinomas operated with a curative intent at a single large tertiary hospital in Madrid (Spain) between 2006 and 2012. None of the patients received adjuvant chemotherapy. We reviewed the histopathological slides and constructed a tissue microarray (TMA) of three representative areas to perform immunohistochemical staining for TRIM72. In our series 30 patients (31.7%) recurred after a median follow-up of 17.5 months. Lack of immunohistochemical expression of TRIM72 in the tumor was significantly and independently associated to recurrence. A recent report by Chen et al. has shown that TRIM72 can be measured in plasma for colon carcinoma detection as an alternative to CEA or CA19.9, with lower levels in patients with carcinoma. Our report is the first one to show that lower immunohistochemical expression of TRIM72 predicts recurrence in colon stage II carcinoma. We feel this predictive influence can be related to its crucial role as a central regulator in many signaling pathways (PI3K-AKT, ERK). As an ubiquitin ligase, the lack of TRIM72 could increase the levels of several potential oncogenic molecules and therefore lead to a more aggressive phenotype. It remains to be shown whether chemotherapy could change the clinical behaviour of this bad prognosis group. We propose TRIM72 immunohistochemical analysis as a potential tool to predict recurrence risk in stage II colon carcinoma patients. Our results should be confirmed in larger series, but could open the way to management strategies refinement in this early stage group of patients.

Rivality index neighbourhood algorithm with density and distances weighted schemes for the building of robust QSAR classification models with high reliable applicability domain.

The rivality index (RI) is a normalized distance measurement between a molecule and their first nearest neighbours providing a robust prediction of the activity of a molecule based on the known activity of their nearest neighbours. Negative values of the RI describe molecules that would be correctly classified by a statistic algorithm and, vice versa, positive values of this index describe those molecules detected as outliers by the classification algorithms. In this paper, we have described a classification algorithm based on the RI and we have proposed four weighted schemes (kernels) for its calculation based on the measuring of different characteristics of the neighbourhood of molecules for each molecule of the dataset at established values of the threshold of neighbours. The results obtained have demonstrated that the proposed classification algorithm, based on the RI, generates more reliable and robust classification models than many of the more used and well-known machine learning algorithms. These results have been validated and corroborated by using 20 balanced and unbalanced benchmark datasets of different sizes and modelability. The classification models generated provide valuable information about the molecules of the dataset, the applicability domain of the models and the reliability of the predictions.

Robust QSAR prediction models for volume of distribution at steady state in humans using relative distance measurements.

The building of quantitative structure-activity relationship (QSAR) models for the in silico prediction of volume distribution for drugs at steady-state levels is vital for the selection of potential drugs at the synthesis stage. Using molecular descriptor matrixes, some regression models presenting low accuracy have been proposed, mainly due to the difficulty of compiling an appropriate dataset and the lack of information on dataset representation. In this paper, we use a benchmark dataset of very diverse drugs for the development of predictive models for volume distribution based on the use of relative distance matrixes as the input data to QSAR algorithms. Support vector machine, complex tree, bagged tree and Gaussian process regression algorithms were tested for fingerprint, similarity and relative distance matrixes used as input data, and the results of the built models were compared. Relative distance matrixes generated robust regression models in the training and external validation stages performed using cross-validation, obtaining values for correlation coefficient, bias, slope and root-mean-square error close to the ideal. Relative distance matrixes were also used for the design of classification models, obtaining excellent results with values of accuracy and area under receiver operating characteristic (AUC) close to 100%.

QSAR classification and regression models for ß-secretase inhibitors using relative distance matrices.

The development of robust QSAR models to predict the activity of molecules of ß-secretase inhibitors is an area of interest due to the increase of Alzheimer's disease in patients in the global population. In this paper, we present a proposal based on the use of relative distance matrices as input data to the QSAR algorithms. These matrices store measurements of distances between the structural characteristics of pairs of molecules and between the molecules and a structural pattern extracted from the whole data set, thus efficiently representing a correlation between structural changes and activity. For the building of the classification and regression models support vector machine, tree complex and Gaussian process algorithms have been used; and for the validation of the models cross-validation, bootstrapping and y-randomizing techniques have been applied. The results obtained are close to 100% in accuracy and area under receiver operating characteristic values in classification, and close to 1.0 for r2 and 0.1 for root mean square error in regression in training and in external validation, proving the 'goodness' of the proposal.

Molecular activity prediction by means of supervised subspace projection based ensembles of classifiers.

This paper proposes a method for molecular activity prediction in QSAR studies using ensembles of classifiers constructed by means of two supervised subspace projection methods, namely nonparametric discriminant analysis (NDA) and hybrid discriminant analysis (HDA). We studied the performance of the proposed ensembles compared to classical ensemble methods using four molecular datasets and eight different models for the representation of the molecular structure. Using several measures and statistical tests for classifier comparison, we observe that our proposal improves the classification results with respect to classical ensemble methods. Therefore, we show that ensembles constructed using supervised subspace projections offer an effective way of creating classifiers in cheminformatics.

Allergic Contact Dermatitis Caused by Acrylates in Long-Lasting Nail Polish. / Dermatitis alérgica de contacto por acrilatos en esmaltes permanentes.

The first reported cases of allergic contact dermatitis from acrylates in manicure procedures in relation to the application of porcelain nails were published decades ago. The frequency of sensitization has increased due to the introduction of the so-called permanent nail polish containing photo-bonded acrylates, mainly involving the beauticians who apply them, and to a lesser extent, the consumers. The recent commercialized permanent polish kits for domestic use could trigger even higher degrees of sensitization. In this article, the clinical features, diagnostic procedures, treatment and preventive measures are described. Acrylates are present in a wide range of sources including multiple medical materials. Sensitization caused by a merely aesthetic procedure might end up having an eventual important impact in the future consumer's health which is why restrictive policies should be implemented limiting its use to qualified professionals and banning the indiscriminate sale of domestic kits.

Allergic contact dermatitis from acrylic nails in a flamenco guitarist.

Acrylates are molecules that are well known for their strong sensitizing properties. Historically, many beauticians and individuals using store-bought artificial nail products have developed allergic contact dermatitis from acrylates. More recently, the use of acrylic nails among flamenco guitarists to strengthen their nails has become very popular. A 40-year-old non-atopic male patient working as a flamenco guitarist developed dystrophy, onycholysis and paronychia involving the first four nails of his right hand. The lesions were confined to the fingers where acrylic materials were used in order to strengthen his nails to play the guitar. He noticed improvement whenever he stopped using these materials and intense itching and worsening when he began reusing them. Patch tests were performed and positive results obtained with 2-hydroxyethyl methacrylate (2-HEMA), 2-hydroxyethyl acrylate (2-HEA), ethyleneglycol-dimethacrylate (EGDMA) and 2-hydroxypropyl methacrylate (2-HPMA). The patient was diagnosed with occupational allergic contact dermatitis likely caused by acrylic nails. Artificial nails can contain many kinds of acrylic monomers but most cases of contact dermatitis are induced by 2-HEMA, 2-HPMA and EGDMA. This is the first reported case of occupational allergic contact dermatitis from acrylates in artificial nails in a professional flamenco guitar player. Since the practice of self-applying acrylic nail products is becoming very popular within flamenco musicians, we believe that dermatology and occupational medicine specialists should be made aware of the potentially increasing risk of sensitization from acrylates in this setting.

Regulation of cell death receptor S-nitrosylation and apoptotic signaling by Sorafenib in hepatoblastoma cells.

Nitric oxide (NO) plays a relevant role during cell death regulation in tumor cells. The overexpression of nitric oxide synthase type III (NOS-3) induces oxidative and nitrosative stress, p53 and cell death receptor expression and apoptosis in hepatoblastoma cells. S-nitrosylation of cell death receptor modulates apoptosis. Sorafenib is the unique recommended molecular-targeted drug for the treatment of patients with advanced hepatocellular carcinoma. The present study was addressed to elucidate the potential role of NO during Sorafenib-induced cell death in HepG2 cells. We determined the intra- and extracellular NO concentration, cell death receptor expression and their S-nitrosylation modifications, and apoptotic signaling in Sorafenib-treated HepG2 cells. The effect of NO donors on above parameters has also been determined. Sorafenib induced apoptosis in HepG2 cells. However, low concentration of the drug (10nM) increased cell death receptor expression, as well as caspase-8 and -9 activation, but without activation of downstream apoptotic markers. In contrast, Sorafenib (10 µM) reduced upstream apoptotic parameters but increased caspase-3 activation and DNA fragmentation in HepG2 cells. The shift of cell death signaling pathway was associated with a reduction of S-nitrosylation of cell death receptors in Sorafenib-treated cells. The administration of NO donors increased S-nitrosylation of cell death receptors and overall induction of cell death markers in control and Sorafenib-treated cells. In conclusion, Sorafenib induced alteration of cell death receptor S-nitrosylation status which may have a relevant repercussion on cell death signaling in hepatoblastoma cells.

Effect of ß-lactoglobulin A and B whey protein variants on cheese yield potential of a model milk system.

Cheese yield mainly depends on the amount and proportion of milk constituents; however, genetic variants of the proteins present in milk may also have an important effect. The objective of this research was to study the effect of the variants A and B of ß-lactoglobulin (LG) on cheese yield using a model system consisting of skim milk powder fortified with different levels of a mixture containing α-lactalbumin and ß-LG genetic variants (A, B, or A-B) in a 1:2 ratio. Fortified milk samples were subjected to pasteurization at 65 °C for 30 min. Miniature cheeses were made by acidifying (pH=5.9) fortified milk and incubating with rennet for 1h at 32 °C. The clot formed was cut, centrifuged at 2,600 × g for 30 min at 20 °C and drained for determining cheese yield. Cheese-yielding capacity was expressed as actual yield (grams of cheese curd per 100g of milk) and dry weight yield (grams of dried cheese curd per 100g of milk). Free-zone capillary electrophoresis was used for determining ß-LG A or B recovery in the curd during rennet-induced coagulation. The presence of ß-LG variant B resulted in a significantly higher actual and dried weight cheese yield than when A or A-B were present at levels ≤ 0.675% of whey protein (WP) addition. Results of free-zone capillary electrophoresis allowed us to infer that ß-LG B associates with the casein micelles during renneting, as shown by an increase in the recovery of this variant in the curd when ß-LG B was added up to a maximum at 0.45% (equivalent to 0.675% WP). In general, actual or dried weight cheese yield increased as WP addition was increased from 0.225 to 0.675%. However, when WP addition ranged from 0.675 to 0.90%, a drastic drop in cheese yield was observed. This behavior may be because an increase in the aggregation of casein micelles with a concomitant inclusion of whey protein in the gel occurs at low levels of WP addition, whereas once the association of WP with the casein micelles reach a saturation point at addition levels higher than 0.675%, rearrangements of the gel network result in larger whey expulsion and syneresis. This knowledge is expected to be useful to maximize cheese yield and optimize processing conditions during cheese and cheese analogs manufacturing.