Increased Th17-Related Cytokine Serum Levels in Patients With Multiple Polyps of Unexplained Origin

OBJECTIVES: Most patients with multiple colonic polyps do not have a known genetic or hereditary origin. Our aim was to analyze the presence of inflammatory cytokines and levels of glucose, insulin, and C-reactive protein (CRP) in patients with multiple colonic polyps. METHODS: Eighty-three patients with 10 or more adenomatous or serrated polyps and 53 control people with normal colonoscopy were included. Smoking habits were registered, and glucose, CRP, and basal insulin in the serum/blood were measured. Quantification of IL-2, IL-4, IL-6, IL-10, IL-11, IL-17A, and IL-23 cytokine levels in the serum was performed by a high-sensitivity enzyme-linked immunosorbent assay. RESULTS: Smoking and diabetes were more prevalent in those with colonic polyps than in the control people (67% vs 16%, P = 0.001; 11% vs 2%, P = 0.048). In addition, the cytokine serum levels were higher, i.e., IL-2 (P = 0.001), IL-4 (P = 0.001), IL-6 (P = 0.001), IL-17A (P = 0.001), IL-23 (P = 0.014), and CRP (P = 0.003). Adjusting for sex, smoking, and diabetes in a multivariate analysis, IL-2, IL-4, IL-6, IL-17A, and IL-23 remained independently elevated in cases with multiple polyps. DISCUSSION: These results indicate that immune responses mediated by Th17 cells may be involved in the pathogenesis of multiple colonic polyps

Oncogenic driver mutations predict outcome in a cohort of head and neck squamous cell carcinoma (HNSCC) patients within a clinical trial

234 diagnostic formalin-fixed paraffin-embedded (FFPE) blocks from homogeneously treated patients with locally advanced head and neck squamous cell carcinoma (HNSCC) within a multicentre phase III clinical trial were characterised. The mutational spectrum was examined by next generation sequencing in the 26 most frequent oncogenic drivers in cancer and correlated with treatment response and survival. Human papillomavirus (HPV) status was measured by p16INK4a immunohistochemistry in oropharyngeal tumours. Clinicopathological features and response to treatment were measured and compared with the sequencing results. The results indicated TP53 as the most mutated gene in locally advanced HNSCC. HPV-positive oropharyngeal tumours were less mutated than HPV-negative tumours in TP53 (p < 0.01). Mutational and HPV status influences patient survival, being mutated or HPV-negative tumours associated with poor overall survival (p < 0.05). No association was found between mutations and clinicopathological features. This study confirmed and expanded previously published genomic characterization data in HNSCC. Survival analysis showed that non-mutated HNSCC tumours associated with better prognosis and lack of mutations can be identified as an important biomarker in HNSCC. Frequent alterations in PI3K pathway in HPV-positive HNSCC could define a promising pathway for pharmacological intervention in this group of tumours

A snapshot of cancer-associated thromboembolic disease in 2018-2019: First data from the TESEO prospective registry

BACKGROUND: The ever-growing complexity of cancer-associated thrombosis (CAT), with new antineoplastic drugs and anticoagulants, distinctive characteristics, and decisions with low levels of evidence, justifies this registry. METHOD: TESEO is a prospective registry promoted by the Spanish Society of Medical Oncology to which 34 centers contribute cases. It seeks to provide an epidemiological description of CAT in Spain. RESULTS: Participants (N=939) with CAT diagnosed between July 2018 and December 2019 were recruited. Most subjects had advanced colon (21.4%), non-small cell lung (19.2%), and breast (11.1%) cancers, treated with dual-agent chemotherapy (28.4%), monochemotherapy (14.4%), or immune checkpoint inhibitors (3.6%). Half (51%) were unsuspected events, albeit only 57.1% were truly asymptomatic. Pulmonary embolism (PE) was recorded in 571 (58.3%); in 120/571 (21.0%), there was a concurrent deep venous thromboembolism (VTE). Most initially received low molecular weight heparin (89.7%). Suspected and unsuspected VTE had an OS rate of 9.9 (95% CI, 7.3-non-computable) and 14.4 months (95% CI, 12.6-non-computable) (p=0.00038). Six-month survival was 80.9%, 55.9%, and 55.5% for unsuspected PE, unsuspected PE admitted for another reason, and suspected PE, respectively (p<0.0001). The 12-month cumulative incidence of venous rethrombosis was 7.1% (95% CI, 4.7-10.2) in stage IV vs 3.0% (95% CI, 0.9-7.1) in stages I-III. The 12-month cumulative incidence of major/clinically relevant bleeding was 9.6% (95% CI, 6.1-14.0) in the presence of risk factors. CONCLUSION: CAT continues to be a relevant problem in the era of immunotherapy and targeted therapies. The initial TESEO data highlight the evolution of CAT, with new agents and thrombotic risk factors

Polymorphisms in the BER and NER pathways and their influence on survival and toxicity in never-smokers with lung cancer

Polymorphisms in DNA repair pathways may play a relevant role in lung cancer survival in never-smokers. Furthermore, they could be implicated in the response to chemotherapy and toxicity of platinum agents. The aim of this study was to evaluate the influence of various genetic polymorphisms in the BER and NER DNA repair pathways on survival and toxicity in never-smoker LC patients. The study included never-smokers LC cases diagnosed from 2011 through 2019, belonging to the Lung Cancer Research In Never Smokers study. A total of 356 never-smokers cases participated (79% women; 83% adenocarcinoma and 65% stage IV). Survival at 3 and 5 years from diagnosis was not associated with genetic polymorphisms, except in the subgroup of patients who received radiotherapy or chemo-radiotherapy, and presented with ERCC1 rs3212986 polymorphism. There was greater toxicity in those presenting OGG1 rs1052133 (CG) and ERCC1 rs11615 polymorphisms among patients treated with radiotherapy or chemo-radiotherapy, respectively. In general, polymorphisms in the BER and NER pathways do not seem to play a relevant role in survival and response to treatment among never-smoker LC patients

FCGR polymorphisms in the treatment of rheumatoid arthritis with Fc-containing TNF inhibitors

[EN] Objectives: Reproducible association of a functional polymorphism in FCGR2A with response to a TNF inhibitor (TNFi) in patients with rheumatoid arthritis (RA) led us to explore other Fc?R functional polymorphisms. Methods: Functional polymorphisms FCGR3A F158V, FCGR2B I223T and promoter VNTR in FCGRT were analyzed in up to 429 patients with RA. Response to TNFi was recorded during standard care at 3, 6 and 12 months of follow-up. Fixed effects meta-analysis of studies addressing FCGR3A F158V polymorphism, which is the most studied of these polymorphisms, was conducted with inverse variance weighting. Results: None of the functional polymorphisms were associated with change in DAS28. Meta-analysis of the seven studies (899 patients) with available data addressing association of FCGR3A F158V with response to TNFi in RA showed no association (OR: 1.11, 95% CI: 0.8-1.5; p = 0.5). Conclusion: None of the three functional polymorphisms in Fc?R genes showed association with response to TNFi in patients with RA. These negative results were obtained in spite of the larger size of this study relative to previous studies addressing the same polymorphisms. In addition, meta-analysis of FCGR3A F158V was also negative against the results provided by previous studies

The subpopulation pattern of eel sperm is affected by post-activation time, hormonal treatment and thermal regime

[EN] There has been a marked reduction in natural stocks of eels (genus Anguilla) over the past 60 years, and the culture of eels is still based on the capture of very large quantities of juveniles. It is necessary to close the life cycle in captivity in order to ease the pressure on wild populations. The aims of the present study were to evaluate sperm subpopulations (through cluster analysis of computer-aided sperm analysis data) in the European eel (Anguilla anguilla) and to assess the effects of motility acquisition time after activation (i.e. at 30, 60 and 90 s), the thermal regimen (i.e. 10 degrees C (T10) or 15 degrees C (T15) and up to 20 degrees C, or constant at 20 degrees C (T20)) and hormonal treatments (i.e. human chorionic gonadotropin (hCG), recombinant (r) hCG or pregnant mare serum gonadotropin (PMSG)) on these subpopulations. In all cases, we obtained three subpopulations of spermatozoa: low velocity and linear (S1); high velocity with low linearity (S2); and high velocity and linear (S3; considered high quality). Total motility and S1 were affected by acquisition time; thus, 30 s is recommended as the standard time for motility acquisition. When eels were kept at 20 degrees C (T20), motility data fitted quadratic models, with the highest motility and proportion of S3 between Weeks 8 and 12 after the first injection. Lower temperatures (T10, T15) delayed spermiation and the obtaining of high-quality spermatozoa (S3), but did not seem to alter the spermiation process (similar subpopulation pattern). Conversely, the hormonal treatments altered both the dynamics of the subpopulation pattern and the onset of spermiation (with PMSG delaying it). Total motility and the yield of S3 with the widely used hCG treatment varied throughout the spermiation period. However, using rhCG allowed us to obtain high-quality and constant motility for most of the study (Weeks 7-20), and the S3 yield was also higher overall (61.8 +/- 1.3%; mean +/- s.e.m.) and more stable over time than the other hormonal treatments (averaging 53.0 +/- 1.4%). Using T20 and rhCG would be more economical and practical, allowing us to obtain a higher number of S3 spermatozoa over an extended time.This study was funded by the European Community's 7th Framework Program under the Theme 2 'Food, Agriculture and Fisheries, and Bio-technology', grant agreement no. 245257 (PRO-EEL) and Generalitat Valenciana (ACOMP/2012/086). VG and MCV have predoctoral grants from the Spanish Ministry of Economy and Competitiveness (AGL2010-16009) and Universitat Politecnica de Valencia (UPV) PAID Program (2011-S2-02-6521), respectively. DSP was supported by a contract cofinanced by Ministry of Science and Innovation (MICINN) and UPV (PTA2011-4948-I). FM-P was supported by the Ramon y Cajal program (MICINN, RYC-2008-02560).Gallego Albiach, V.; Vilchez Olivencia, MC.; Peñaranda, D.; Pérez Igualada, LM.; Herraez, MP.; Asturiano Nemesio, JF.; Martinez-Pastor, F. (2015). The subpopulation pattern of eel sperm is affected by post-activation time, hormonal treatment and thermal regime. Reproduction, Fertility and Development. 27(3):529-543. https://doi.org/10.1071/RD13198S52954327

Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1