Polymorphisms associated with adalimumab and infliximab response in moderate-to-severe plaque psoriasis

Aims. This study evaluated the influence of pharmacogenetics in psoriatic patients treated with adalimumab and/or infliximab. Materials & methods: Prospective observational study evaluating the association of 124 polymorphisms with the response to adalimumab or infliximab (PASI75) in patients with moderate-to-severe plaque psoriasis at 3 months (n = 95) and 6 months of treatment (n = 90). Significant SNPs for univariate analysis were subjected to multivariate analysis. Results: Five SNPs were associated with PASI75 at 3 months: rs6661932 (IVL), rs2546890 (IL-12B), rs2145623 (NFKBIA), rs9304742 (ZNF816A) and rs645544 (SLC9A8). Furthermore, rs1061624 (TNFR1B) was associated with PASI75 at 6 months. Conclusion: Nevertheless, these biomarkers should be validated in large-scale studies before implementation in clinical practice

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

Influential Factors of Breastfeeding after Assisted Reproduction: A Spanish Cohort

The impact of assisted reproduction techniques (ART) when starting to breastfeed is an important issue that has been sparsely addressed in scientific literature and yet has contradictory results. This study aims to determine the relation between the mode of fertilization and breastfeeding by means of a retrospective longitudinal cohort study that included newborns and mothers who gave birth between 2012 and 2019 in a third-level regional hospital. Data were collected from a total of 11,285 women and newborns, of which 302 (2.6%) used ART. Logistic regression was used to establish models that determine the administration of exclusive breastfeeding (BF). Among the 1208 analyzed participants, 30% conceived using fertility treatment. In this group of participants, BF was less prevalent, both in the delivery room (25.8% versus 45.5%; p < 0.001) and when discharged from hospital (42.1% versus 57.9%; p < 0.001). Healthy newborns and BF in the delivery room were predictors of BF when discharged. On the other hand, the use of ART, an Apgar score lower than 7 at birth, the use of an epidural and a premature or underweight baby are considered negative predictors of exclusive BF when discharged. It is necessary to offer greater support for all mothers regarding BF, especially those who have conceived through ART, even more so in those cases that involve an epidural and/or caesarean section, starting throughout the dilation process

Conocimientos tradicionales relativos a la biodiversidad agrícola

La biodiversidad agrícola, a diferencia de la silvestre, requiere la acción continuada de los agricultores para su conservación, ya que las plantas cultivadas dependen de la intervención humana, con actividades como la selección, la siembra, el abonado, la poda u otras prácticas agrícolas para su supervivencia. Desde la revolución agrícola del Neolítico hasta la actualidad, estas prácticas y conocimientos han ido generando y conservando una gran diversidad, amenazada a partir de la segunda mitad del siglo XX por las causas que se han indicado anteriormente.Peer reviewe

Trends and outcome of neoadjuvant treatment for rectal cancer: A retrospective analysis and critical assessment of a 10-year prospective national registry on behalf of the Spanish Rectal Cancer Project

Introduction: Preoperative treatment and adequate surgery increase local control in rectal cancer. However, modalities and indications for neoadjuvant treatment may be controversial. Aim of this study was to assess the trends of preoperative treatment and outcomes in patients with rectal cancer included in the Rectal Cancer Registry of the Spanish Associations of Surgeons. Method: This is a STROBE-compliant retrospective analysis of a prospective database. All patients operated on with curative intention included in the Rectal Cancer Registry were included. Analyses were performed to compare the use of neoadjuvant/adjuvant treatment in three timeframes: I)2006–2009; II)2010–2013; III)2014–2017. Survival analyses were run for 3-year survival in timeframes I-II. Results: Out of 14, 391 patients, 8871 (61.6%) received neoadjuvant treatment. Long-course chemo/radiotherapy was the most used approach (79.9%), followed by short-course radiotherapy ± chemotherapy (7.6%). The use of neoadjuvant treatment for cancer of the upper third (15-11 cm) increased over time (31.5%vs 34.5%vs 38.6%, p = 0.0018). The complete regression rate slightly increased over time (15.6% vs 16% vs 18.5%; p = 0.0093); the proportion of patients with involved circumferential resection margins (CRM) went down from 8.2% to 7.3%and 5.5% (p = 0.0004). Neoadjuvant treatment significantly decreased positive CRM in lower third tumors (OR 0.71, 0.59–0.87, Cochrane-Mantel-Haenszel P = 0.0008). Most ypN0 patients also received adjuvant therapy. In MR-defined stage III patients, preoperative treatment was associated with significantly longer local-recurrence-free survival (p < 0.0001), and cancer-specific survival (p < 0.0001). The survival benefit was smaller in upper third cancers. Conclusion: There was an increasing trend and a potential overuse of neoadjuvant treatment in cancer of the upper rectum. Most ypN0 patients received postoperative treatment. Involvement of CRM in lower third tumors was reduced after neoadjuvant treatment. Stage III and MRcN + benefited the most

Rotura uterina en gestante con cesárea anterior tras maniobra de Kristeller: Reporte de caso

Antecedentes: La rotura uterina es una complicación rara (0,7%), pero grave en la práctica obstétrica. La cesárea previa es el factor predisponente más importante para este evento catastrófico. Su aparición espontánea es extremadamente rara, se estima que ocurre en 1 de 8000 a 1 de 15.000 partos. Objetivo: Divulgar un caso clínico de interés para la comunidad médica por la asociación de la rotura uterina con un factor de riesgo poco establecido como es la presión fúndica (Maniobra de Kristeller). Caso clínico: Gestante de 28 años con antecedentes personales de cesárea por placenta previa hace 5 años. Parto actual de inicio espontáneo y terminación tras presión fúndica. A las 6 horas del parto la paciente refiere sensación de pérdida de orina hematúrica, dolor abdominal y malestar general. La ecografía abdominal revela en cara posterior de vejiga una solución de continuidad. Ante el diagnóstico de sospecha de rotura uterina se realiza laparotomía exploradora evidenciando rotura completa circunferencial a nivel cervico vaginal y desgarro vesical posterior de unos 10 cm. Se realizan suturas término-terminal vagino-cervical y del desgarro vesical. Postoperatorio con buena evolución. Conclusiones: La presión del fondo uterino durante el parto puede originar rotura uterina incluso sobre el útero sin cicatrices. Ante el diagnóstico de sospecha de rotura uterina, sobretodo en presencia de algún factor de riesgo, debemos actuar con rapidez, siendo la clave la laparotomía exploradora. La maniobra de Kristeller debe ser evitada especialmente en cesáreas previas

Validity of two-dimensional ultrasound for determining extreme foetal weights to term

The aim of this study was to assess the validity of ultrasound carried out within seven days prior to birth at term for the calculation of full term estimated foetal weight (EFW) in order to diagnose extreme foetal weight, performed using a single-center retrospective cohort study of 2500 pregnant women. Ultrasound calculations of EFW with a standard error of less than 10% showed an accuracy ratio of 75.1% for the total sample. This percentage was similar for appropriate for gestational age (78.6%) and normal foetal weights (77.5%) but decreased significantly (p < .01) in the case of extreme foetal weights. The simple error increased in both the high and low EFWs, taking on positive values for the low weights and negative values for the high weights. As for the percentage error values, there was a tendency for positive errors for low weights and negative errors for high weights; this led to a tendency to overestimate low foetal weights and underestimate high foetal weights.IMPACT STATEMENT What is already known on this subject? Two-dimensional ultrasound is currently the principal tool used in obstetrics to evaluate foetal growth, mainly through the calculation of EFW. Foetal weight represents an important prognostic factor in perinatal results, with a greater risk of adverse effects in cases of extreme foetal weights. In this sense, there are few studies that assess the validity of EFW calculations focussing on extreme foetal weights to term. What do the results of this study add? The ultrasound estimates of EFW with an error lower than 10% in the seven days prior to birth showed an accuracy ratio of 75.1% for the total sample. This percentage was similar to appropriate for gestational age weights (78.6%) and of normal weights (77.5%), but decreased significantly (p < .01) in the case of extreme foetal weights: small for gestational age (52.1%), large for gestational age (68.2%), microsomia (49.1%), and macrosomia (61%). Likewise, we found high specificity and low sensitivity for ultrasound diagnosis of extreme foetal weights. What are the implications of these findings for clinical practice and/or future research? The validity of ultrasound EFW is influenced by extreme foetal weights, with a tendency to overestimate low weights and underestimate high weights, which represents a clinically important finding

CNVs Associated with Different Clinical Phenotypes of Psoriasis and Anti-TNF-Induced Palmoplantar Pustulosis

Background: Psoriasis can present different phenotypes and could affect diverse body areas. In contrast to the high effectiveness of biological drugs in the treatment of trunk and extremities plaque psoriasis, in palmoplantar phenotypes and in plaque scalp psoriasis, these same drugs usually have reduced efficacy. Anti-TNF drugs could induce the appearance of palmoplantar pustulosis (PPP) in patients with other inflammatory diseases. The objective of this study is to identify if there are DNA Copy Number Variations (CNVs) associated with these different clinical phenotypes, which could justify the differences found in clinical practice. Moreover, we intend to elucidate if anti-TNF-induced PPP has a similar genetic background to idiopathic PPP. Methods: Skin samples were collected from 39 patients with different patterns of psoriasis and six patients with anti-TNF-induced PPP. The CNVs were obtained from methylation array data (Illumina Infinium Human Methylation) using the conumee R package. Results: No significant CNVs were found between the different phenotypes and the locations of psoriasis compared. Nevertheless, we found two significant bins harboring five different genes associated with anti-TNF-induced PPP in patients with a different background other than psoriasis. Conclusions: Our results may help to predict which patients could develop anti-TNF-induced PPP