SfM-3DULC: Reliability of a new 3D wound measurement procedure and its accuracy in projected area

[EN] Three-dimensional (3D) wound measurement lacks a gold standard to test accuracy. It is useful to develop procedures to scan wounds and reconstruct their 3D model with low-cost techniques. We present a new procedure (Structure from Motion [SfM]-3DULC) that uses photographs for measuring nine wound variables. We also propose a new variant of ImageJ in which an orthophoto is used to measure the projected area (Ortho-ImageJ). In addition, we compare the wound measurements made by dermatologists and non-experts. A group of five experts in dermatology and five non-specialists measured 33 leg wounds five times per procedure. Intra-rater and inter-rater reliability scores of SfM-3DULC were evaluated with the intraclass correlation coefficient (ICC 2,1). The accuracy of the two new procedures (SfM-3DULC and Ortho-ImageJ) in the measurement of projected area was assessed by comparing their values with those obtained using ImageJ, with the Wilcoxon matched-pairs signed rank test (alpha = 0.05). This test was also used to analyse the differences between the measurements made by dermatologists and non-experts. All the variables measured by dermatologists using SfM-3DULC showed excellent scores of intra-rater reliability (ICC > 0.99) and inter-rater reliability (ICC > 0.98). No significant differences between the three procedures were found when comparing their projected area values. Significant differences between the measurements of dermatologists and non-experts were found in most of the variables: circularity coefficient, perimeter, projected area, surface area, and reference surface area. The wound measurement procedure SfM-3DULC has an excellent reliability, is accurate for the measurement of projected area, and can be used by dermatologists for wound monitoring in everyday clinical practice.The authors thank Mr. Ramon Dura Mora and the Unidad de Enfermeria, ulceras y Heridas complejas La Fe. This work is part of the Ph.D. research of D.S-J., which is supported by a grant from Generalitat Valenciana-Conselleria de Educacion, Investigacion, Cultura y Deporte, and the European Social Fund (ACIF/2018/160).Sánchez-Jiménez, D.; Buchón Moragues, FF.; Escutia-Muñoz, B.; Botella-Estrada, R. (2022). SfM-3DULC: Reliability of a new 3D wound measurement procedure and its accuracy in projected area. International Wound Journal. 19(1):44-51. https://doi.org/10.1111/iwj.13595S445119

Development of Computer Vision Applications to Automate the Measurement of the Dimensions of Skin Wounds

[EN] This paper shows the progress in the development of two computer vision applications for measuring skin wounds. Both applications have been written in Python programming language and make use of OpenCV and Scipy open source libraries. Their objective is to be part of a software that calculates the dimensions of skin wounds in an objective and reliable way. This could be useful in the clinical follow-up, assessing the evolution of skin wounds, as well as in research, comparing the efficacy of different treatments. Merging these two applications into a single one would allow to generate two-dimensional results in real time, and three-dimensional results after a few hours of processingThis work is part of the Ph.D. research of D.S., which is supported by a grant from Generalitat Valenciana - Consellería de Educación, Investigación, Cultura y Deporte and the European Social Fund (ACIF/2018/160)Sánchez-Jiménez, D.; Buchón Moragues, FF.; Escutia-Muñoz, B.; Botella-Estrada, R. (2019). Development of Computer Vision Applications to Automate the Measurement of the Dimensions of Skin Wounds. Proceedings. 19(18):1-4. https://doi.org/10.3390/proceedings2019019018S14191

Heteroduplex analysis of T-cell receptor γ gene rearrangement as an adjuvant diagnostic tool in skin biopsies for erythroderma

Erythroderma, defined as red skin covering most of the body surface often accompanied or followed by exfoliation, is the clinical manifestation of at least six different underlying etiologies with allergic or irritant contact dermatitis, atopic/asteotic dermatitis, pityriasis rubra pilaris (PRP), psoriasis, and seborrheic dermatitis accounting for the majority of cases. Approximately 10% of cases are due to adverse drug reactions with roughly another 10% due to cutaneous T-cell lymphoma (CTCL), predominantly mycosis fungoides, or leukemia. It is clear from multiple studies that the clinical diagnosis of the underlying entity is often difficult, as these diseases can present in a very similar fashion. A skin biopsy is usually employed in this setting as a diagnostic tool. However, the histopathologic diagnosis of the underlying cause is complicated by the subtlety of the distinguishing histologic features. In this situation, an ancillary technique demonstrating the presence of a monoclonal T-cell proliferation could help to rule in or out CTCL in cases that clinically and histopathologically do not allow a definitive diagnosis. Methods: We retrospectively studied 25 biopsies from sixteen patients who presented to the Stanford Dermatology Clinic with erythroderma. We examined the specimens morphologically and analyzed the gamma chain of the T-cell receptor (TCR- γ) by polymerase chain reaction (PCR) followed by heteroduplex analysis for clonality. We then correlated the results of our PCR and heteroduplex analyses with the patients’ clinical outcomes. Results: Four biopsies, from three patients, contained clonal TCR-γ rearrangements; the four biopsies, all of which were equivocal histologically, correlated to diagnoses of mycosis fungoides (MF) or SÉzary syndrome (SS). Twenty-one biopsies contained polyclonal T-cell populations. Eighteen of these biopsies represent patients with inflammatory dermatoses. Three of these biopsies, all of which were taken from a single patient, correlate to a diagnosis of MF. Conclusion: TCR-γ PCR heteroduplex analysis seems to represent an important adjuvant diagnostic tool that, used in conjunction with histopathology and clinical history, could help to clarify the underlying etiology of erythroderma.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72286/1/j.1600-0560.2001.280703.x.pd

DNA copy number variation associated with anti-tumour necrosis factor drug response and paradoxical psoriasiform reactions in patients with moderate-to-severe psoriasis

Biological drugs targeting tumour necrosis factor are effective for psoriasis. However, 30–50% of patients do not respond to these drugs and may even develop paradoxical psoriasiform reactions. This study search-ed for DNA copy number variations that could predict anti-tumour necrotic factor drug response or the ap-pearance of anti-tumour necrotic factor induced pso-riasiform reactions. Peripheral blood samples were collected from 70 patients with anti-tumour necrotic factor drug-treated moderate-to-severe plaque pso-riasis. Samples were analysed with an Illumina 450K methylation microarray. Copy number variations were obtained from raw methylation data using conumee and Chip Analysis Methylation Pipeline (ChAMP) R packa-ges. One copy number variation was found, harbouring one gene (CPM) that was significantly associated with adalimumab response (Bonferroni-adjusted p-value < 0.05). Moreover, one copy number variation was identified harbouring 3 genes (ARNT2, LOC101929586 and MIR5572) related to the development of paradoxical psoriasiform reactions. In conclusion, this study has identified DNA copy number variations that could be good candidate markers to predict response to ada-limumab and the development of anti-tumour necrotic factor paradoxical psoriasiform reactions.This study was supported by Instituto de Salud Carlos III PI 13/01598 and the Ministry of Science and Innovation and the European Regional Development’s funds (FEDER). Conflicts of interest. FA-S has been a consultant or investigator in clinical trials sponsored by the following pharmaceutical companies: Abbott, Alter, Chemo, Farmalíder, Ferrer, GlaxoSmithKline, Gilead, Janssen-Cilag, Kern, Normon, Novartis, Servier, Teva, and Zambon. ED has potential conflicts of interest (advisory board member, consultant, grants, research support, participation in clinical trials, honoraria for speaking, and research support) with the following pharmaceutical companies: AbbVie (Abbott), Amgen, Janssen-Cilag, Leo Pharma, Novartis, Pfizer, MSD, Lilly and Celgene. ML-V has potential conflicts of interest as she has participated in clinical trials or as consultant with Abbvie (Abbott), Galderma, Janssen-Cilag, Leo Pharma, Pfizer, Novarties, Lilly, Almirall and Celgene. MCO-B has potential conflicts of interest (honoraria for speaking and research support) with Janssen-Cilag and Leo Pharma. The other authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. AS-T has served as a consultant and/or paid speaker for and/or participated in clinical trials sponsored by companies that manufacture drugs used for the treatment of psoriasis, including AbbVie, Celgene, Janssen-Cilag, LEO Pharma, Lilly, Novartis and Pfizer. RB-E has served as a consultant and/or paid speaker for and/or participated in clinical trials sponsored by companies that manufacture drugs used for the treatment of psoriasis, including AbbVie, Celgene, Janssen-Cilag, LEO Pharma, Lilly, Novartis and Pfizer

Erythroderma: A clinical study of 97 cases

BACKGROUND: Erythroderma is a rare skin disorder that may be caused by a variety of underlying dermatoses, infections, systemic diseases and drugs. METHODS: We reviewed the clinical, laboratory and biopsy material of 97 patients diagnosed with erythroderma who were treated in our department over a 6-year period (1996 through 2002). RESULTS: The male-female ratio was 1.85:1. The mean age at diagnosis was 46.2 years. The most common causative factors were dermatoses (59.7%), followed by drug reactions (21.6%), malignancies (11.3%) and idiopathic causes (7.2%). Carbamazepine was the most common drug (57.1%). The best clinicopathologic correlation was found in cutaneous T-cell lymphoma and pityriasis rubra pilaris related erythroderma. Apart from scaling and erythema that were present in all patients, pruritus was the most common finding (97.5%), followed by fever (33.6%), lymphadenopathy (21.3%), edema (14.4%) and hyperkeratosis (7.2%). CONCLUSION: This study outlines that underlying etiologic factors of erythroderma may show geographic variations. Our series had a high percentage of erythroderma secondary to preexisting dermatoses and a low percentage of idiopathic cases. There was no HIV-infected patient among our series based on multiple serum antibody tests. The clinical features of erythroderma were identical, irrespective of the etiology. The onset of the disease was usually insidious except in drug-induced erythroderma, where it was acute. The group associated with the best prognosis was that related to drugs

Epigenetic activation of a cryptic TBC1D16 transcript enhances melanoma progression by targeting EGFR

Metastasis is respoMetastasis is responsible for most cancer-related deaths, and, among common tumor types, melanoma is one with great potential to metastasize. Here we study the contribution of epigenetic changes to the dissemination process by analyzing the changes that occur at the DNA methylation level between primary cancer cells and metastases. We found a hypomethylation event that reactivates a cryptic transcript of the Rab GTPase activating protein TBC1D16 (TBC1D16-47 kDa; referred to hereafter as TBC1D16-47KD) to be a characteristic feature of the metastatic cascade. This short isoform of TBC1D16 exacerbates melanoma growth and metastasis both in vitro and in vivo. By combining immunoprecipitation and mass spectrometry, we identified RAB5C as a new TBC1D16 target and showed that it regulates EGFR in melanoma cells. We also found that epigenetic reactivation of TBC1D16-47KD is associated with poor clinical outcome in melanoma, while conferring greater sensitivity to BRAF and MEK inhibitors

Hospitalización a domicilio

Hospitalització domiciliària; Revisió sistemàtica; Evidència científicaHospitalización domiciliaria; Revisión sistemática; Evidencia científicaHome hospitalization; Systematic review; Scientific evidenceInforme que evalúa la hospitalización domiciliaria en términos de eficacia y seguridad y analiza la situación de la hospitalización domiciliaria en Cataluña y EspañaInforme que avalua l’hospitalització domiciliària en termes d'eficàcia i seguretat i analitza la situació de l’hospitalització domiciliària a Catalunya i EspanyaReport that evaluates home hospitalization in terms of efficacy and safety and it analyzes the situation of home hospitalization in Catalonia and Spain

Effect of sex in systemic psoriasis therapy: Differences in prescription, effectiveness and safety in the BIOBADADERM prospective cohort

The effect of sex on systemic therapy for psoriasis has not been well studied. The aim of this study was to analyse a large multicentre Spanish cohort of 2,881 patients with psoriasis (58.3% males), followed from January 2008 to November 2018, to determine whether sex influences prescription, effectiveness of therapy, and the risk of adverse events. The results show that women are more likely than men to be pre-scribed biologics. There were no differences between men and women in effectiveness of therapy, measur-ed in terms of drug survival. Women were more likely to develop adverse events, but the difference in risk was small and does not justify different management. Study limitations include residual confounding and the use of drug survival as a proxy for effectiveness.The BIOBADADERM project is promoted by the Fundación Piel Sana Academia Española de Dermatología y Venereología, which receives financial support from the Spanish Medicines and Health Products Agency (Agencia Española de Medicamentos y Productos Sanitarios) and from pharmaceutical companies (Abbott/Abbvie, Pfizer, MSD, Novartis, Lilly, Janssen and Almirall)

Proyecto HAD 2020: una propuesta para consolidar la hospitalización a domicilio en España

Hospital at home (HAH) appeared in Spain 36 years ago with the opening of several units. The initial push was truncated by the lack of political leadership and sometimes clinical as well. The current reality offers an irregular implementation with a wide disparity of assistance and resource models. The Sociedad Española de Hospitalización a Domicilio (SEHAD) has not played either the expected scientific or professional leadership roles. The “Plan HAD2020: key of the future” was designed as revulsive. This is an ambitious 4-year project to consolidate HAH as a care modality. Its deployment consists of five phases. Preparation: the foundations of the strategic plan (EP) were established. Situation analysis: a national survey was carried out on the 106 operational units (data 2014). Validation of the EP: contributions and proposals of action of the members of SEHAD. National Congress 2016: presentation and approval of EP conclusions and proposals. EP deployment phase: it will be extended until 2020 and will be executed by various teams of referents spread over five lines of work.The final objective set for the year 2020 is: to come up with a more homogenous care model; to promote the training and professional recognition of those who work in the HAD; that each hospital in Spain has a HAH unit; recognition and empowerment by the national health system.HAD2020 has marked an inflection point in the SEHAD. The traced path and the effort of all the HAH professionals will allow reaching the vision which the pioneers of the HAH in Spain pursued.La Hospitalización a Domicilio (HAD) apareció en España hace 36 años con la apertura de diversas unidades. El empuje inicial fue truncado por la falta de liderazgo político y en ocasiones también clínico. La realidad actual ofrece una implantación irregular con disparidad de modelos asistenciales y de recursos. La Sociedad Española de Hospitalización a Domicilio (SEHAD) no ha jugado el papel de liderazgo científico y profesional esperado. Se diseñó el «Plan HAD2020: clave de futuro» como revulsivo. Se trata de un ambicioso proyecto a 4 años para consolidar la HAD como modalidad asistencial. Su despliegue consta de cinco fases. Preparación: se establecieron las bases del plan estratégico (PE). Análisis de situación: se realizó una encuesta nacional a las 106 unidades operativas (datos 2014). Validación del PE: aportaciones y propuestas de actuación de los miembros de SEHAD. Congreso Nacional 2016: presentación y aprobación de conclusiones y propuestas del PE. Fase de despliegue PE: se extenderá hasta el año 2020 y la ejecutarán diversos equipos referentes, repartidos en cinco líneas de trabajo.El objetivo final fijado para el año 2020 consiste en: consensuar un modelo asistencial más homogéneo; promover la formación y reconocimiento profesional de quienes trabajan en la HAD; que cada hospital de España tenga una unidad de HAD; reconocimiento y potenciación por el sistema de salud nacional.HAD2020 ha marcado un punto de inflexión en la SEHAD. El camino trazado y el esfuerzo de todos los profesionales HAD permitirán alcanzar aquella visión que persiguieron los pioneros de la HAD en España

Down-Regulation of the Interferon Signaling Pathway in T Lymphocytes from Patients with Metastatic Melanoma

BACKGROUND: Dysfunction of the immune system has been documented in many types of cancers. The precise nature and molecular basis of immune dysfunction in the cancer state are not well defined. METHODS AND FINDINGS: To gain insights into the molecular mechanisms of immune dysfunction in cancer, gene expression profiles of pure sorted peripheral blood lymphocytes from 12 patients with melanoma were compared to 12 healthy controls. Of 25 significantly altered genes in T cells and B cells from melanoma patients, 17 are interferon (IFN)-stimulated genes. These microarray findings were further confirmed by quantitative PCR and functional responses to IFNs. The median percentage of lymphocytes that phosphorylate STAT1 in response to interferon-α was significantly reduced (Δ = 16.8%; 95% confidence interval, 0.98% to 33.35%) in melanoma patients (n = 9) compared to healthy controls (n = 9) in Phosflow analysis. The Phosflow results also identified two subgroups of patients with melanoma: IFN-responsive (33%) and low-IFN-response (66%). The defect in IFN signaling in the melanoma patient group as a whole was partially overcome at the level of expression of IFN-stimulated genes by prolonged stimulation with the high concentration of IFN-α that is achievable only in IFN therapy used in melanoma. The lowest responders to IFN-α in the Phosflow assay also showed the lowest gene expression in response to IFN-α. Finally, T cells from low-IFN-response patients exhibited functional abnormalities, including decreased expression of activation markers CD69, CD25, and CD71; T(H)1 cytokines interleukin-2, IFN-γ, and tumor necrosis factor α, and reduced survival following stimulation with anti-CD3/CD28 antibodies compared to controls. CONCLUSIONS: Defects in interferon signaling represent novel, dominant mechanisms of immune dysfunction in cancer. These findings may be used to design therapies to counteract immune dysfunction in melanoma and to improve cancer immunotherapy