Pharmacogenetic biomarkers for secukinumab response in psoriasis patients in real-life clinical practice.

BACKGROUND: Prediction of the response to a biological treatment in psoriasis patients would allow efficient treatment allocation. OBJECTIVE: To identify polymorphisms associated with secukinumab response in psoriasis patients in a daily practice setting. METHODS: We studied 180 SNPs in patients with moderate-to-severe plaque psoriasis recruited from 15 Spanish hospitals. Treatment effectiveness was evaluated by absolute PASI ≤3 and ≤1 at 6 and 12 months. Individuals were genotyped using a custom Taqman array. Multiple logistic regression models were generated. Sensitivity, specificity and area under the curve (AUC) were analysed. RESULTS: A total of 173 patients were studied at 6 months, (67% achieved absolute PASI ≤ 3 and 65% PASI ≤ 1) and 162 at 12 months (75% achieved absolute PASI ≤ 3 and 64% PASI ≤ 1). Multivariable analysis showed the association of different sets of SNPs with the response to secukinumab. The model of absolute PASI≤3 at 6 months showed best values of sensitivity and specificity. Four SNPs were associated with the capability of achieving absolute PASI ≤ 3 at 6 months. rs1801274 (FCGR2A), rs2431697 (miR-146a) and rs10484554 (HLCw6) were identified as risk factors for failure to achieve absolute PASI≤3, while rs1051738 (PDE4A) was protective. AUC including these genotypes, weight of patients and history of biological therapy was 0.88 (95% CI 0.83-0.94), with a sensitivity of 48.6% and specificity of 95.7% to discriminate between both phenotypes. CONCLUSION: We have identified a series of polymorphisms associated with the response to secukinumab capable of predicting the potential response/non-response to this drug in patients with plaque psoriasis.

Epigenetics in Non-tumor Immune-Mediated Skin Diseases.

Epigenetics is the study of the mechanisms that regulate gene expression without modifying DNA sequences. Knowledge of and evidence about how epigenetics plays a causative role in the pathogenesis of many skin diseases is increasing. Since the epigenetic changes present in tumor diseases have been thoroughly reviewed, we believe that knowledge of the new epigenetic findings in non-tumor immune-mediated dermatological diseases should be of interest to the general dermatologist. Hence, the purpose of this review is to summarize the recent literature on epigenetics in most non-tumor dermatological pathologies, focusing on psoriasis. Hyper- and hypomethylation of DNA methyltransferases and methyl-DNA binding domain proteins are the most common and studied methylation mechanisms. The acetylation and methylation of histones H3 and H4 are the most frequent and well-characterized histone modifications and may be associated with disease severity parameters and serve as therapeutic response markers. Many specific microRNAs dysregulated in non-tumor dermatological disease have been reviewed. Deepening the study of how epigenetic mechanisms influence non-tumor immune-mediated dermatological diseases might help us better understand the role of interactions between the environment and the genome in the physiopathogenesis of these diseases.

Teaching of clinical ultrasonography to undergraduates: students as mentors. / Enseñanza de la ecografía clínica en el pregrado: los estudiantes como mentores.

BACKGROUND: Ultrasonography is a highly useful diagnostic technique that supplements traditional physical examinations. OBJECTIVE: To demonstrate that students previously trained in clinical ultrasonography are capable of instructing other students in a similar manner in a short period of time ("peer mentoring"). METHODOLOGY: Five medical students in their 5th year, trained in abdominal and cardiac ultrasonography by physicians with experience, instructed 24 other students in the same procedure. The training consisted of an online theoretical course and practical training lasting about 12hours, in which each student had to perform 6 basic abdominal planes and 4 basic cardiac planes on 20 healthy volunteers. Subsequently, the students underwent an objective assessment test on healthy models performed by expert physicians in clinical ultrasonography. RESULTS: The students managed to correctly identify 90.2% of the basic abdominal planes, except for the left coronal (spleen and left kidney) and subcostal (gallbladder) planes, with slightly lower success rates of 82.5% and 80%, respectively. Due to the greater difficulty of obtaining cardiac planes, the success rate was lower: 70.3%, in the subxiphoid, short parasternal and four chamber planes. The cardiac plane with the fewest errors in identification was the parasternal long plane (90% success). We observed no statistically significant differences between the results (teaching capacity) of the various mentors. CONCLUSION: Medical students are capable of instructing other colleagues (peer mentoring) on the basic aspects of abdominal and cardiac ultrasonography after a relatively short training period.