Search

Background Background: The feasibility of anti-TNF discontinuation in inflammatory bowel disease (IBD) must be proven in clinical trials including patients in clinical, endoscopic, and radiologic remission at the time of anti-TNF withdrawal to make recommendations for clinical practice. Aims Primary: to compare the rates of clinical remission at 1 year in patients who discontinue anti-TNF treatment vs. those who continue treatment. Secondary objectives: to know the effect of anti-TNF withdrawal on relapse-free time, mucosal healing and safety; and to identify predictive factors for relapse. Methods Prospective, quadruple-blind, multicentre, randomised, controlled trial. Patients with ulcerative colitis (UC) or Crohn’s disease (CD) in clinical remission for > 6 months were randomised to maintain anti-TNF treatment [maintenance arm (MA)] or to withdraw it [withdrawal arm (WA)]. Patients who were on infliximab (IFX) received IFX 5 mg/kg or an intravenous placebo every 8 weeks, while patients on adalimumab (ADA) received subcutaneous ADA 40 mg or placebo every other week. Patients were followed-up until month 12 or up to the time of clinical relapse, whichever came first. Inclusion and exclusion criteria, trial scheme and definitions are summarized in figures 1a, 1b and 1c. Results were analysed by intention-to-treat (ITT) and by per-protocol (PP). Local investigators were blinded to faecal calprotectin (FC) and IFX and ADA trough levels. On-site monitoring was performed to assess data quality. Results 159 patients were screened, from whom 140 were randomised and comprised the ITT cohort: 70 allocated to the MA and 70 to the WA. Fifteen patients dropped out before the end of follow-up (12 months or relapse), leaving 63 patients in the MA and 62 patients in the WA for the PP analysis. The characteristics of patients in the MA and WA were similar (figure 2). The proportions of patients who maintained clinical remission -59/70 (84%), 95% confidence interval (CI)=74-92% in the MA vs. 53/70 (76%), 95%CI=64-85% in the WA- and who remained without significant endoscopic lesions at the end of follow-up were similar between groups (figures 3a, 3b, 3c). Only the proportion of patients with FC >250 mg/g was higher in the WA at the end of follow-up (figure 3d). Maintenance of clinical remission was no different between groups (figure 4). The same percentage of patients in both groups had at least one adverse event (69%). The proportion of patients with serious adverse events was also similar between groups (4% in MA vs. 7% in WA). Conclusion Anti-TNF withdrawal in selected IBD patients in clinical, endoscopic, and radiologic remission could be feasible without an increase in the risk of clinical relapse. Long-term follow-up of these patients is warranted.

Resumen Antecedentes En la Comunidad de Madrid desde 2005 la vacunacion antineumococica en personas con 60 anos o mas se ha realizado con vacuna polisacarida 23-valente (VNP23). En enero de 2018, se cambio por vacuna conjugada 13-valente (VNC13). El objetivo del estudio fue analizar los datos de vacunacion antineumococica y evaluar la puesta en marcha de la nueva pauta de vacunacion en adultos en dicha comunidad. Material y metodos Estudio transversal de base poblacional para determinar la cobertura vacunal antineumococica mediante revision retrospectiva del registro de la historia de vacunacion de personas con 60 anos o mas residentes en la Comunidad de Madrid. Resultados Hasta 2018, un 83% de la poblacion vacunada frente a neumococo en la Comunidad de Madrid lo fue con VNP23, un 6% con VNC13 y un 11% con ambas. En 2018, 92.593 personas de 60 anos o mas recibieron vacuna antineumococica. El 96,5% procedieron de registros de Atencion Primaria. Las dosis de VNC13 superaron a las de VNP23 en en las personas con 60 anos o mas en todos los grupos de edad. Un total de 78.660 personas con 60 anos o mas fueron vacunadas con VNC13 (el 19,5% sin factores de riesgo; el 67,3% con enfermedad cronica de base; el 2,5% del grupo de alto riesgo y el 10,7% pertenecientes a ambos grupos). Conclusiones En 2018, siguiendo las recomendaciones de la Comunidad de Madrid, 6.639 personas no fueron correctamente vacunadas con VNC13 y 72.021 (91,6%) si lo fueron. La mayor confusion se produjo en las personas con 60 anos o mas sin factores de riesgo que tenian una VNP23 previa y no precisaban otra vacuna, pero recibieron una VNC13 sin cumplir con la pauta recomendada.

Background Patients with inflammatory bowel disease (IBD) are often classified as ulcerative colitis (UC) and Crohn’s disease (CD). However, in some cases this categorization is not possible and these patients are labelled as inflammatory bowel disease unclassified (IBDU) -or indeterminate colitis if histologic analysis of surgical specimens is possible-.The aims of this study were to compare the prognosis and therapeutic requirements in patients with IBDU and UC, and to identify potential predictive factors of reclassification as UC or CD. Methods Retrospective, observational, multicenter and case-control study of Spanish ENEIDA registry promoted by GETECCU. IBDU patients were identified from 18 centers. Every case of IBDU was matched with 2 patients of ulcerative colitis of the same hospital by sex, age at diagnosis and disease extent (in the patchy colitis subgroup, every case was matched with 1 extensive colitis and 1 left colitis). Results 231 IBDU patients and 469 UC patients were included. Only 15 IBDU patients met current criteria of indeterminate colitis. In the IBDU group 59.7% patients were males and the mean of age at diagnosis was 43.3 years. Disease extent was distributed in 14 proctitis, 59 left-sided colitis, 87 extensive colitis and 53 patchy colitis. 13.9% had rectal sparing and 31.9% presented ileitis. Thirteen percent were smokers at diagnosis, 5.6% had perianal disease and 15.9% had extraintestinal manifestations. Table 1: baseline characteristics of IBDU and UC group. When comparing IBDU to UC patients, there were no statistical differences between proportion of patients that needed immunosuppressants (35.7% vs 37.7%, p=0.558) and biological therapy (27.3% vs 24.3%, p=0.415). Regarding surgery for medically refractory disease, UC patients had higher surgical rates, although these differences did not reach statistical significance (2.6% vs 0.5%, p= 0.062). Figure 1: immunosuppressants, biological and surgery rates. Overall mortality rates were similar in both groups (5.1% in IBDU vs 2.6% in UC); with only one case related to IBD in IBDU group. During follow-up, 67 IBDU patients (31%) were reclassified (32 UC, 34 CD, 1 indeterminate colitis). 25% of patients were reclassified within 46 months of follow-up (Figure 2: Kaplan-Meier curve of reclassification). Neither clinical, biochemical (C- reactive protein, albumin, hemoglobin) nor endoscopic variable (rectal sparing, ileitis) was associated with change in diagnosis. Conclusion In clinical practice, there were no statistical differences in prognosis, therapeutic requirements and surgical treatment between IBDU and UC patients. Two thirds of patients remained classified as IBDU during the follow-up. No predictive factors of reclassification have been identified.

Background Ustekinumab is an effective drug in Crohn′s Disease (CD) and most frequently used dose is subcutaneous (sc), 90 mg /, 8 weeks. With the usual sc doses (90 mg every, 8–12 weeks) some patients will only partially respond or experience secondary loss of response. In this situation, shortening of the administration interval (e.g., every, 4 or, 6 weeks) or a reinduction dose has been proposed. Another unexplored option is intravenous (IV) administration at regular intervals when shortening sc dose is not effective enough. Methods We conducted a retrospective study to evaluate the effectiveness of IV ustekinumab at regular intervals (usually every, 4–6 weeks) in patients with insufficient efficacy or loss of response to, 90 mg sc every, 4–6 weeks. All patients had active Ulcerative colitis (UC) or Crohn′s disease (CD) defined by partial Mayo score (pMS) or Harvey Bradshaw Index (HBI)>, 4 points and/or persistent biomarker elevation (calprotectin>, 250 µg/g) and/or endoscopic or radiological evidence of disease activity. We obtained data from, 79 patients (73 CD and, 6 with ulcerative colitis (UC)). Levels of fecal calprotectin before and after starting ustekinumab IV was available for, 44 patients and trough levels of drug for, 48 patients. Results Baseline characteristics of the included patients are shown in Table, 1. Complicated forms (B2-B3;, 60,6%) predominated and perianal disease was present in, 35.4% of patients. Only, 3 patients were naïve to biological treatments, 41.8% had received at least one and, 54,5% more than, 2. The mean follow-up after the first IV administration was, 13.22 months (IQR, 2–37 months). Last dose used before the start of ustekinumab IV was, 90 mg /, 6 weeks in, 31.6% and, 90 mg /, 4 weeks in, 68.4% of the patients. After, 12 weeks of the first IV dose, 43% of patients achieve clinical remission (HBI Conclusion Patients who lose response to the intensified dose of ustekinumab sc could benefit from intravenous administration as maintenance treatment. This strategy achieves clinical remission in, 60% of the patients and allows to maintain the treatment in, 80% of them for at least, 12 months.

Background The 21st century has witnessed advances in endoscopic surveillance technology such as high-definition imaging and virtual or dye-based chromoendoscopy, which have led to increased detection of dysplasia. It is unknown the rates of new dysplastic lesions or cancer progression with these techniques though it seems lower than previously described. Methods We developed a multicenter, population-based and retrospective cohort from 7 Spanish hospitals from the Group of Inflammatory bowel disease of Castilla Y Leon (GEICYL) including sequentially all patients with inflammatory bowel disease and colonic dysplastic lesions completely resected (R0) in surveillance with dye-based indigo carmine chromoendoscopy between January 2013 and December 2019, with a minimum endoscopic follow-up of 12 months. The aim was to evaluate the risk of developing more advanced metachronous neoplasia during follow-up, analysing possible associated risk factors. Results A total of 99 patients and 148 index lesions (145 low-grade dysplasias [LGD] and 3 high-grade dysplasias [HGD]) with a medium follow-up of 48.76 months (IQR: 36.34 – 67.15) were included. Patients and IBD baseline characteristics are reflected in table 1. During follow-up, 37 patients developed 97 new dysplastic lesions (92 LGD, 4 HGD and 1 CRC) and 1 patient developed multifocal invisible dysplasia (3 HGD). The overall incidence rate for new dysplastic lesions was 0.23 per 100 patient-year, 1.15 per 100 patients at 5 years and 2.29 per 100 patients at 10 years (Figure 1). Personal history of dysplasia was associated with higher risk of developing any grade of dysplasia during follow-up (p 0.025), meanwhile, left colon lesions was associated with a lower risk (p 0.043). 6 patients developed more advanced lesions (5 patients HGD and 1 CCR) with an incidence rate at year and 10 years of 1% and 14% respectively; LGD lesion >1cm was a risk factor for developing HGD or CRC (p 0.041), meanwhile LGD lesion < 1 cm was a protective factor (p 0.013) (table 2,3). 1/8 patients (13%) with HGD lesions developed CRC during follow-up. 3 patients were colectomized (2 by HGD and 1 by CRC). Neither mesalamine treatment or immunosuppressive or biological treatment were associated with a lower risk of dysplasia development. Conclusion Risk of dysplasia progression to advanced neoplasia and specifically risk of new neoplastic lesions after endoscopic resection of colitis-associated dysplasia are very low in our cohort with dye-chromoendoscopy. Personal history of dysplasia, as risk factor, and left colon location, as protective factor, were associated with new dysplastic lesions. Finally, size above 1 cm was the only risk factor for progression to advanced lesions.

Background Some patients with Inflammatory Bowel Disease (IBD) who are treated with anti-TNFα therapy develop a drug-induced psoriasis (IP) as an adverse event. There are some therapeutic approaches, being more frequent to change the biologic therapy to ustekinumab, effective and approved for the treatment of both entities. This could be the best option, but available data are lacking and it could increase the risk of IBD relapse. Our aim is to assess the management of anti-TNF IP in IBD, and the subsequent evolution of both diseases in a large nationwide cohort of patients. Methods Retrospective, observational multicenter study from the prospectively maintained Spanish ENEIDA registry. Participants were patients with IBD and anti-TNFα IP. At baseline, psoriasis severity was classified as mild, moderate or severe, and remission was defined as the resolution of skin lesions, clinical response as an improvement without complete resolution, and no response as the absence of improvement. IBD clinical activity was defined based on Harvey-Bradshaw Index and Partial Mayo Score. All items were evaluated when available at baseline and 16, 32 and 54 weeks. Results Anti-TNFα IP was reported in 234 patients (CD: 185, UC: 46, unclassified IBD: 3). SWAP strategy was chosen in 76 patients (32.5%), most of them to ustekinumab (90.8%), 71 (30.3%) patients continued anti-TNF, 49 (20.9%) discontinued it, and in 38 (16.2%) a switch to a second anti-TNF was made. The decision to continue or not anti-TNF was associated to psoriasis severity (p Conclusion Evaluating IBD activity and psoriasis severity is essential before modifying IBD treatment due to IP. Continuing anti-TNF treatment in mild psoriasis cases, and considering SWAP to ustekinumab in moderate-severe ones, could be a suitable strategy.

Background The use of ustekinumab (UST) and vedolizumab (VDZ) as first line therapy for inflammatory bowel disease (IBD) is increasing due to safety reasons and contraindications of anti-TNFs. However, there are no studies evaluating their efficacy and safety in clinical practice under these circumstances. Thus, our aims were to describe bionaïve patients’ characteristics starting VDZ or UST and to evaluate treatment persistence of these drugs and their safety profile in this scenario. Methods Descriptive, retrospective and multicenter study based on the ENEIDA registry (a large, prospectively maintained database of the Spanish Working Group in IBD –GETECCU). All IBD patients never exposed to biological agents who started VDZ or UST as first-line biological treatment were identified. Results Out of 29,450 IBD patients ever exposed to biological drugs included in the ENEIDA registry, 924 patients met the inclusion criteria. Of these, 366 (40%) started UST and 558 (60%) VDZ as first line biological therapy. UST group: 48% women, 90% Crohn's disease (43% ileal; 13% colic; 43.5% ileocolic; 31% upper gastrointestinal involvement; 25% stricturing behaviour; 12% penetrating, 18% perianal disease), 10% ulcerative colitis (74% extensive, 17% left-sided, 9% proctitis), 27% had extraintestinal manifestations (EIM). Median age at the beginning of UST was 57 years (IQR 57-70), 17% patients had a past history of malignancy and, 34% had associated comorbidities. UST indication was luminal activity except in 2% for perianal disease and 5% for EIM. At the end of follow-up (median 14 months [IQR 6-30]), 12 patients (3.3%) developed adverse effects (AEs) that led to treatment discontinuation in the majority of them (92%). VDZ group: 44% women, 42% Crohn's disease (44% ileal; 18% colic; 38% ileocolic; 25% upper gastrointestinal involvement; 28% stricturing behaviour; 13% penetrating; 7% perianal disease), 58% ulcerative colitis (50% extensive, 42% left-sided, 8% proctitis), 17% had EIM. The median age at the beginning was 61 years (IQR 48-71), 24% had past history of malignancy and, 34% associated comorbidities. The indication was exclusively luminal activity. At the end of follow-up (median 21 months [IQR 8-36]), 36 patients (6.5%) had AEs, that lead to treatment withdrawal in 67% of them (24 patients). Cumulative treatment persistence rates were 78%, 60% and 50% for VDZ and 85%, 75% and 66% for UST at 12, 24 and 36 months, respectively (P Conclusion In clinical practice, VDZ and UST are used first-line particularly in elderly patients with comorbidities. Both treatments have a good safety profile and a high persistence of treatment, being superior for ustekinumab.

Background Female sex has been associated with a worse response to anti-TNF drugs and with discontinuation of these drugs in immune-mediated diseases. Data in Inflammatory Bowel Disease (IBD) are unclear. The aims of study are to assess possible differences in long-term treatment persistence and safety of biological drugs between women and men with IBD. Methods Multicenter observational study carried out with data from the ENEIDA registry. Patients diagnosed with Crohn's disease (CD) or ulcerative colitis (UC) who receive or have received biological drugs, and have had a minimum treatment follow-up of 6 months, were included. We evaluated the first biological treatment used in the patient. Statistic analysis; Regression logistic models were used for safety evaluation. Kaplan-Meier curves, Log-Rank test and COX regression were used to treatment persistance. Results A total of 51,595 patients with IBD were evaluated [ 25,947 with CD (13238 men and 12709 women) and 25,648 with UC (13596 men and 12052 women)]. Mean follow up of 13 years. Biologic use: 28.7% of the evaluated patients had been treated with at least one biologic drug. Biologics use in UC was less common in women than in men (15.5% vs. 17.2%, OR (95%CI): 0.88 (0.81-0.94), p= 0.001) and there were no differences between sexes in CD ( 45.7% in men, 44.7% in women). Infliximab (IFX) and adalimumab (ADA) were the most used drugs (in 8914 and 5269 patients, respectively). Safety evaluation. Women suffered more frequently adverse effects to IFX and ADA than men, being the withdrawal of IFX and ADA due to adverse effects also significantly more frequent in women than in men. Biological treatment persistence in patients with IBD was longer in men than in women [median 3.1 years vs. 2.3 years, p < 0.001]. Female sex was a risk factor of biologic discontinuation [adjusted hazard ratio [aHR] (95%CI): 1.20 (1.14-1.25), p Figure 1. Conclusion 1.The use of biologics in ulcerative colitis seems to be higher in men than in women. 2. Female sex is an independent risk factor for the development of adverse effects to IFX and ADA and for the discontinuation of these drugs. 3. The long-term persistence of IFX and ADA (as first biological treatments) is low, being higher in men compared to women.

Early husbandry practices that include herd management and the use of livestock areas such as sheepfold caves can be analysed in the context of different disciplines (e.g. zooarchaeology, micromorphology, and archaeobotany). In this study, a new and standard method for the determination of bile acids and steroidal hormones that incorporates microwave extraction-liquid chromatography-mass spectrometry was used. This method has been applied successfully to analyse Neolithic fumier deposit facies from the El Mirador cave, a location that was used as a prehistoric sheepfold and is located in the Atapuerca range (Burgos, Spain). The results obtained demonstrated that the analysis of bile acids can be useful for the identification of remains of ruminant residues in the facies studied. In addition, the progesterone/deoxycholic acid ratio has been used as a possible biomarker to improve our understanding of flock management, including the separation of pregnant and nursing ewes from the rest of the herd to avoid the rejection of the lamb and keep them safe and healthy. The authors thank the technical and human support provided by the Alava Central Service of Analysis of SGIker (UPV/EHU, MINECO, GV/ EJ, ERDF, and ESF) and Paula Rivero for the elaboration of the graphical abstract. Patricia Martín is grateful for her postdoctoral fellowship to Juan de la Cierva Subprogramme (FJCI-2016-29045) with financial sponsorship from the Spanish Ministry of Economy, Industry, and Competitiveness and for her recent "Maria de Maeztu" excellenceaccreditation from the Spanish Minstry of Science and Innovation (CEX2019-000945-M), and to Ane Gorostizu-Orkaiztegi for her pre- doctoral fellowships to the University of the Basque Country. This work was funded by the Department of Industry, Innovation, Commerce, and Tourism of the Basque Government (SAI12/25 Project), the Spanish Ministry of Science, Innovation and University (PGC 2018-093925-B- C32 project) and by the Basque Government, Research Groups of the Basque University System (Project No. IT925-16).

Currently, aluminum stub with carbon adhesive devices are used to collect inorganic gunshot residues (GSR) from the hands of a shooter. In an ideal shooting case, the gunshot particles do not persist for more than 2 h in the hands of the shooter, provided that the hands have not been washed. However, for forensic analysis and inference, the extended persistence of GSR would be desirable. This study investigates a novel GSR sampling and detection protocol. Sampling was performed in the nostrils using swab devices impregnated in ethylenediaminetetraacetic acid (EDTA). The GSRs persisted for longer periods in nasal mucus than on the hands, and particles were detected 6 h after shooting occurred. The analytical determination was conducted by scanning laser ablation-inductively coupled plasma-mass spectrometry (SLA-ICPMS) which enable the identification of the number of particles and their elemental composition. Seventeen isotope signals corresponding to 13 C, 205 Tl and 15 analytes that are usually associated with the composition of GSR residues were monitored: 27 Al, 29 Si, 31 P, 33 S, 35 Cl, 39 K, 44 Ca, 57 Fe, 60 Ni, 63 Cu, 66 Zn, 118 Sn, 121 Sb, 137 Ba, and 208 Pb. The SLA technique enabled the reduction of the swab analysis time to 40 min. The effectiveness of this methodology was evaluated with two types of firearms: a pistol and a shotgun. The results indicated that the methodology proposed for the analysis of the nasal GSR was effective and that it can improve or complement the forensic analyses and inferences presented in a court.

Introduction: Management of Helicobacter pylori infection (H. pylori) re-quires co- treatment with proton pump inhibitors (PPIs) and the use of an- tibiotics to achieve successful eradicationAims & Methods: To evaluate the role of PPIs in the eradication of H. py-lori, based on the “European Registry onHelicobacter pylori Management” (Hp- EuReg).The Hp-EuReg is a multicentre, prospective, non-interventional, registry assessing decisions and outcomes of H. pylori management by European gastroenterologists in routine clinical practice. Countries recruiting more than 1, 000 patients were included. Effectiveness was assessed by modi- fied intention-to-treat (mITT). Data were quality reviewed.Results: Overall, 22, 078 patients from 5 countries were analysed. Optimal (»90%) first-line mITT effectiveness was achieved with the following treatments: 14-day clarithromycin- amoxicillin- bismuth quadruple therapy, and 14- day metronidazole-tetracycline-bismuth quadruple therapy, both inde-pendently of the PPI dose prescribed ; in all 10- or 14-day therapies with high-dose PPIs (except with standard 10-day triple therapy) ; in 10-day se-quential and 10- day quadruple clarithromycin-amoxicillin- bismuth, and 10-day quadruple metronidazole- tetracycline- bismuth with standard-dose PPIs. None of the 7-day therapies achieved optimal cure rates re-gardless of the PPI dose used. The PPI dose was significantly associated with the effectiveness of: 10- or 14- day standard triple and quadruple con-comitant therapies, and 10-day quadruple sequential and metronidazole-tetracycline-bismuth therapies. Table 1 details the mITT effectiveness by duration and PPI dose used.Conclusion: In first-lineH. pylori treatment, ≥90% effectiveness is obtained with standard-dose PPIs in 10-day sequential and 10- or 14-day bismuth quadruple therapies and with high-dose PPIs in all 10- or 14-day therapies except with standard 10-day triple therapy.

Introduction: The impact of consensus, prescription choices and efficacy trends on clinical practice over time has not been studied in depth.Aims & Methods: International multicenter prospective non-intervention-al registry aimed to evaluate the decisions and outcomes of H. pyloriman-agement by European gastroenterologists. All infected adult patients were systematically registered at AEG-REDCap e-CRF from 2013 to December 2021. Variables included: previous eradication attempts, prescribed treatment, adverse events, and outcomes. Modified intention- to-treat (mITT) and time trend analyses were performed. Data were subject to quality review.Results: So far 49, 739 patients from 29 European countries have been in-cluded, and 35, 203 (71%) were first-line empirical prescriptions. Overall, the most common prescribed treatments in the 2013-21 period were triple therapies ; however, a shift in antibiotic regimens was identi-fied. Triple therapies decreased from over 50% of prescription in 2013/15 to less than 25% in 2020/21 ; likewise, non-bismuth concomitant therapy use decreased from 21% in 2013/14 to 13% in 2020/21, while three-in-one single- capsuleincreased from 0- 1% in 2014/2015 to 17% in 2020/21. An increase in the average duration of treatments from 9.8 days in 2013 to 13 days in 2021 was identified, as well as the daily high- dose of PPIs increasing from 16% in 2013 to 50% in 2021. Detailed description of most common treatments is shown in Table 1. Re-garding the effectiveness of each specific treatment, no trend was identi-fied (data now shown) ; however, there was a 10% overall improvement in first-line mITT overall effectiveness from 2013 to 2021. Conclusion: European gastroenterological practice is constantly adapting to the newest published evidence and recommendations (reducing the use of triple therapies and increasing both the duration of treatment and the dose of PPIs), with a subsequent progressive improvement in overall effectiveness.

Introduction: Introduction: Randomized clinical trials and meta-analyses, primarily from Asian countries, have reported good effectiveness with high-dose dual therapy (HDDT, i.e., PPIs plus high amoxicillin doses) when prescribed for H. pylorifirst-line or rescue treatment. However, combining amoxicillin with PPIs in the 1990s in several European countries yielded suboptimal results. The objective was to analyse the effectiveness, com-pliance and safety of HDDTin the European real clinical practice.Aims & Methods: Methods: International, multicenter, prospective non- interventional Registry aimed at evaluating the decisions and outcomes of H. pylori management by European gastroenterologists. All infected adult cases treated with HDDT were registered at AEG- REDCap e-CRF up to June 2021. Patients receiving HDDT (amoxicillin 1, 000 mg three times a day plus a PPI), with or without bismuth, in any treatment line and for at least 10 days, were selected for inclusion.Results: Sixty patients received HDDT (98% compliance), 19 of them as first-line and 41 as rescue treatment (2nd–6th line). Overall HDDT effec- tiveness was 52% (per-protocol) and 51% (modified intention-to- treat, mITT). First-line and rescue treatment lines were similarly effective. Cure rates were lower when patients had previously received metronidazole (mITT 32% vs. 70%, p

[EN]The production of artificial anti-CB1 antibodies in nanoparticle format is described using the solid-phase imprinting approach. Instead of whole protein imprinting, a linear C-terminus sequence of the receptor comprising 15 amino acids (458-KVTMSVSTDTSAEAL-472) has been used as template, in accordance with the epitope imprinting approach. This sequence is located intracellularly, and it is involved in coupling to G(i/o) proteins, being responsible for CB1 receptor desensitisation and internalisation. Developed molecularly imprinted materials were found to be in the nanometre scale, with a particle size of 126.4 +/- 10.5 nm at pH 3 (25 oC) and spherical shape. It was also observed that the size was sensible to temperature changes being reduced to 106.3 +/- 15.2 nm at 35 degrees C. Lower critical solution temperature of this polymer was found to be approximate to 33.4 degrees C. The affinity and selectivity of the artificial antibody were assessed through dot blot and Western blot experiments. For the latter, recombinant fusion proteins GST-CB1(414-472) and GST-CB1(414-442) were produced to work respectively as target and negative control proteins. The control protein did not carry the target epitope for being devoid of last 30 amino acids at the C-terminus. The results demonstrated that the anti-CB1 material recognised selectively the target protein, thanks to the presence of the 15-amino acid sequence selected as epitope, which revealed that binding occurred at the C-terminus of the receptor itself. The methodology presented may pave the way for the development of novel imprinted nanomaterials for other proteins included in the superfamily of the G-protein-coupled receptors (GPCR). Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. Funding for this research was provided by the Spanish Ministry of Science, Innovation and Universities (project CTQ2017-85686-R) and by the Basque Government (Research Groups of the Basque University System, Project No IT 1186-19.

Objective. The goal of this work is to experimentally compare the 3D spatial and energy resolution of a semi-monolithic detector suitable for total-body positron emission tomography (TB-PET) scanners using different surface crystal treatments and silicon photomultiplier (SiPM) models. Approach. An array of 1 × 8 lutetium yttrium oxyorthosilicate (LYSO) slabs of 25.8 × 3.1 × 20 mm3 separated with Enhanced Specular Reflector (ESR) was coupled to an array of 8 × 8 SiPMs. Three different treatments for the crystal were evaluated: ESR + RR + B, with lateral faces black (B) painted and a retroreflector (RR) layer added to the top face; ESR + RR, with lateral faces covered with ESR and a RR layer on the top face and; All ESR, with lateral and top sides with ESR. Additionally, two SiPM array models from Hamamatsu Photonics belonging to the series S13361-3050AE-08 (S13) and S14161-3050AS-08 (S14) have been compared. Coincidence data was experimentally acquired using a 22Na point source, a pinhole collimator, a reference detector and moving the detector under study in 1 mm steps in the x- and DOI- directions. The spatial performance was evaluated by implementing a neural network (NN) technique for the impact position estimation in the x- (monolithic) and DOI directions. Results. Energy resolution values of 16 ± 1%, 11 ± 1%, 16 ± 1%, 15 ± 1%, and 13 ± 1% were obtained for the S1 3-ESR + B + RR, S1 3-All ESR, S14-ESR + B + RR, S14-ESR + RR, and S14-All ESR, respectively. Regarding positioning accuracy, mean average error of 1.1 ± 0.5, 1.3 ± 0.5 and 1.3 ± 0.5 were estimated for the x- direction and 1.7 ± 0.8, 2.0 ± 0.9 and 2.2 ± 1.0 for the DOI- direction, for the ESR + B + RR, ESR + RR and All ESR cases, respectively, regardless of the SiPM model. Significance. Overall, the obtained results show that the proposed semi-monolithic detectors are good candidates for building TB-PET scanners.

The synthesis of polymers with tailored properties for the recognition of macromolecules such as proteins is challenging. In this work, the synthesis of a new polymer format, a linear polymer (LP), as the selective recognition element for the globular protein lactoferrin (LF) is proposed as a proof-of-concept study. For the synthesis, a solid-phase strategy using the reversible deactivation radical polymerisation (RDRP) mechanism is proposed. This approach, which is usually used in molecular imprinting, involves the immobilisation of LF on the surface of a solid support, but, unlike classical imprinting, a cross-linker in the polymerisation mixture is not required. Consequently, the copolymer is soluble and flexible, thus overcoming the drawbacks associated with traditional synthetic polymers for macromolecule imprinting. This new polymer format has great potential for replacing natural antibodies in bioassays such as enzyme-linked immunosorbent assays (ELISA), dot blot, western blot, or pull-down. In our case, the linear polymer was used as a recognition element to replace natural antibodies in a LF-selective ELISA. The responses of the linear polymer between LF concentrations of 0.1 nM and 0.25 μM were studied, and a significant difference was observed between the non-specific signals and the signals measured in the presence of the polymeric material. Further, the response versus log concentration curves were fitted to a logistic equation, allowing estimation of the EC50 value: 11.8 ± 1.4 nM. We also confirmed the selective detection of LF using the competitive inhibition of the selective LF-biotin conjugate (LF-Bi) binding to the plastic receptor (LP) for closely related proteins (e.g. those having similar molecular weights or isoelectric points) such as human lysozyme, trypsin, and albumin, which are present in human body fluids. The system presents a cross-reactivity value or selectivity of 1.95% for lysozyme, 0.028% for trypsin, and 0.016% for albumin. The applicability of this method for the determination of urine LF levels in inflammatory and infectious diseases of the human urinary tract is also demonstrated.

Background The HLADQA1*05 variant increases the risk of developing antibodies against infliximab and adalimumab. Whether proactive therapeutic drug monitoring (PTDM) could overcome this immunogenicity remains unknown. The primary aim was to evaluate the influence of the allele HLADQA1*05 on treatment persistence. Methods We performed a single centre retrospective cohort study. IBD patients starting anti-TNF therapy between January, 2017 and March, 2021 were included. HLA DQA1*05 genotype screening was performed during, 2021. PTDM was defined as periodic drug level measurement (≥2 determinations during the first year of treatment and ≥1/annual determination during the following years), regardless of clinical condition, with according dose optimization. Patients not fulfilling these criteria were excluded. Target concentration during induction:, 25–30 mcg/ml (week, 2) and, 20 mcg/ml (week, 6) for Infliximab and >, 10 mcg/ml (week, 2 and, 4) for Adalimumab. During maintenance:, 3–10 mcg/ml for Infliximab and, 8–12 mcg/ml for Adalimumab. Clinical remission was defined as HBI 1 and biochemical remission as a fecal calprotectin Results 126 patients started anti-TNF therapy during the study period. Fourteen were excluded (8 lacked PTDM and, 6 declined the HLA DQA1*05 genotype), thus including, 112 patients with a median follow-up of, 73.9 (IQR:, 35.4–133.1) weeks, 52 (46.4%) HLADQA1*05 positive. Figure, 1 presents baseline characteristics. Combination therapy with thiopurines was more frequent among HLADQA1*05 negative patients (28 (46.7%) vs, 12 (23.1%), p=0.01). During their first year, patients underwent a median of, 3 (IQR, 2–4) drug level measurements. We performed, 497 determinations (4/patient (IQR:3–6);, 149 (30%), drove to dose modifications, 63 (42.3%) among symptomatic patients and, 86 (57.7%) among asymptomatic ones. Primary nonresponses were higher (8.1% vs, 0, p=0.06) among HLADQA1*05 negative patients. The HLADQA1*05 positive presented non-significant higher clinical remission rates at week, 14 (77.9% vs, 73.9%, p=0.69) and, 56 (73.2% vs, 68.4%, p=0.64) (figure 2). Figures, 3 and, 4 presents drug persistence, which was higher among HLADQA1*05 positive patients (HR:, 0.32, 95% CI:, 0.14–0.71, p=0.01). Multivariable Cox regression analysis identified systemic steroids at anti-TNF initiation (Hazard ratio (HR):, 4, 95% CI, 1.7–9.7) as a risk factor and a positive HLA DQA1*05 genotype (HR:0.31 (0.12–0.81)) as a protective factor of treatment cessation. Fig.1 Fig. 2. Fig.3 Fig.4. Conclusion: When PTDM is performed, a positive HLA DQA1*05 genotype does not associate a higher risk of treatment cessation.

Background: After a first eradication attempt, approximately 10-20% of patients will fail to achieve H. pylori eradication. Aims: To evaluate the effectiveness of second-line empirical treatments. Methods: A systematic prospective registry of the clinical practice of European gastroenterologists (31 countries) on H. pylori management was established. All infected adult patients were systematically registered at AEG-REDCap e-CRF until February 2021. Modified intention-to-treat (mITT) and per- protocol (PP) analyses were performed. Results: Overall, 5, 228 patients received a second-line empirical therapy. Overall effectiveness was 84% (both by mITT and PP). Over 97% of patients were compliant. AEs were reported in 28% of the cases. Most frequent second-line prescriptions and effectiveness per antibiotic combination is shown in table 1. After failure of first-line clarithromycin-containing treatment, optimal eradication (>90%) was obtained with moxifloxacin-containing triple therapy, or quadruple therapy with levofloxacin and bismuth. In patients receiving triple regimens containing levofloxacin or moxifloxacin and levofloxacin-bismuth quadruple regimens, cure rates were optimized with 14-day regimens using high doses of proton pump inhibitors (PPIs). However, Pylera® or quadruple therapy with levofloxacin and bismuth achieved consistent eradication rates regardless of the PPI dose, duration of therapy, or previous firstline treatment regimen. Conclusion: Empirical second-line regimens including either 14-day triple therapies with levofloxacin or moxifloxacin, or 14-day levofloxacin-bismuth quadruple or 10-day bismuth quadruple therapies provided optimal effectiveness. However, many other second-line treatments evaluated reported low eradication rates.

In the Community of Madrid since 2005 vaccination against pneumococcus in adults from 60 years of age has been carried out with pneumococcal polysaccharide vaccine (PPV23). In January 2018, the guideline changed in favor of pneumococcal conjugate vaccine (PCV13). The objective of this study was to analyze the data of pneumococcal vaccination and to evaluate the implementation of the new guideline of vaccination against pneumococcus in adults in the Community of Madrid.Cross-sectional study to estimate vaccine coverage by a retrospective review of the record of vaccination history of people ≥60 years resident in the Community of Madrid.In the Community of Madrid until 2018, 83% of the population were vaccinated with PPV23, 6% with PCV13 and 11% with both vaccines. 96.5% came from Primary Care records. The doses administered of PCV13 surpassed those of PPV23 in ≥60 years in all age groups. 78,660 people ≥60 years were vaccinated with PCV13 (19.5% without risk factors, 67.3% with chronic diseases, 2.5% of the high-risk group and 10.7% belonging to both groups).In 2018, following Community of Madrid recommendations, 6,639 people were not properly vaccinated with PCV13 and 72,021 (91.6%) were properly vaccinated. The greatest confusion occurred in people ≥60 years without risk factors who had a previous PPV23 and did not require another vaccine but received a PCV13 without complying with the recommended schedule.

Molecularly imprinted polymers (MIP) have attracted considerable attention as smart materials so far. They are known to be capable of imitating the recognition event that happens biologically in living organisms and, in this light, they have noteworthy been used as substitutes of natural receptors. Traditionally, imprinted polymers have been developed by bulk free radical polymerization (FRP), obtaining rigid polymers, which are lately ground to get fine particles. Bulk synthesis of imprinted polymers was substituted by other polymerization approaches in order to overcome typical drawbacks associated with bulk MIPs. Recently, new polymer syntheses have emerged such as solid phase imprinting which have allowed for obtaining smart materials with higher affinity for the target ligand, achieving binding affinities similar or even higher than natural receptors. Materials obtained this way are known as plastic antibodies. This chapter focuses on recent advances on imprinted polymers as potential substitutes of natural receptors, emphasizing on new synthesis strategies and novel imprinted nanomaterials.

International audience; Alcoholic beverages, especially great wines and spirits, are prime targets for counterfeiters. The simplest form of wine fraud involves fixing counterfeit labels of expensive wines to bottles of less expensive wine. However, time-consuming analytical techniques requiring liquid sampling are mainly used for authentication purposes, which irremediably degrade the value of the bottle. This work aims to develop a new diagnostic tool based on the direct analysis of label matrix and ink in order to obtain valuable information that would enable a preliminary non-destructive authentication. Raman and infrared spectroscopies have been applied for fast, reproducible and discernible molecular characterization since both analytical techniques are strictly non-invasive and do not require sample preparation. They were successfully applied to a selected number of genuine and counterfeited bottles (Pauillac, France) and a series of bottles which goes from 1969 to 2010 belonging to the same producer (Pomerol, France). Raman spectroscopy and infrared spectroscopy showed a great complementarity to clarify the molecular composition of label and inks. As a general overview, pigments are not useful for discrimination purpose in the pairs of original and counterfeited samples. However, several mismatch in label composition were identified, allowing the differentiation among samples. With respect to the second batch of bottles, Raman spectroscopy was able to trace the materials used in labels and inks, giving evidences about the chronologic order of manufacture. Despite the limited number of samples, mainly due to their uniqueness, the classification power of the proposed methodology has been clearly proven.

The assessment of chronic kidney disease (CKD) is performed by means of glomerular filtration rate (GFR), which is calculated from equations using serum creatinine concentration. However, serum creatinine concentration changes according to several factors, and this might endanger CKD diagnosis, especially in early stages of the disease. In addition to metabolic and cardiovascular complications, CKD is related to growth complications and malnutrition. All of these complications lead to a 30 times higher mortality rate in paediatrics suffering from advanced CKD compared to healthy counterparts. Overall, the existence of biomarkers for a defined disease allows earlier diagnosis as well as better response. For that reason, comprehensive research has been performed in adults suffering from CKD aimed at finding new biomarkers, however only a few studies are available in paediatrics with CKD so far, and there is a need for new biomarkers in this population. For that purpose, following targeted and untargeted metabolomics approaches seven potential biomarkers have been found which could be useful for paediatric CKD by comparing metabolic profiles. The use of these metabolites in addition to creatinine enables better differentiation of paediatrics with CKD and control ones, unlike just creatinine itself.; Giltzurrun gutxiegitasun kronikoaren (GGK) ebaluazioa egiten da iragazpen glomerularraren tasaren (IGT) bidez, eta kalkulatzen da serumeko kreatininaren kontzentrazioan oinarritutako ekuazio ezberdinen bidez. Hala ere, serumeko kreatinina kontzentrazioa hainbat faktoreren arabera alda daiteke, eta honek GGKaren diagnostikoa arriskuan jar dezake, bereziki gaixotasunaren fase goiztiarrenetan. Haurretan GGKak arazo metaboliko eta kardiobaskularrez gain, garapen-arazoak eta malnutrizioa eragiten ditu. Haur osasuntsuekin alderatuta, zailtasun horiek 30 aldiz handitzen dute heriotza-tasa GGKaren fase aurreratuenetan dauden haurretan. Orokorrean, gaixotasun jakin baterako biomarkatzaileen presentziak diagnostiko goiztiarragoa eta erantzun hobea ahalbidetzen dute. Hori dela eta, GGK pairatzen duten helduetan ikerketa integrala egin da biomarkatzaile berriak topatzeko, baina populazio pediatrikoan ikerlanak oraindik oso mugatuak dira eta biomarkatzaile berrien beharra dago. Helburu horrekin, haur osasuntsuen eta GGK pairatzen duten haur gaixoen arteko profil metabolikoen konparaketa egin da, metabolomika bideratu zein ez-bideratuak aplikatuz. Ikerketaren ondorioz, GGK pediatrikoaren detekzio goiztiarrean erabilgarri izan daitezkeen zazpi metabolito berri aurkitu dira, kreatinina biomarkatzaile klasikoarekin batera. Metabolito horiek, kreatininarekin batera erabiliz, kreatinina soilaren erabilerarekin alderatuz haur gaixoen eta osasuntsuen artean bereizketa egitea ahalbidetzen dute.

Background Crohn’s disease (CD) is a chronic inflammation of the human gastrointestinal tract. Intestinal conventional dendritic cells (cDC) maintain the balance between immunity against pathogens and tolerance towards nutrients and commensals. However, there is not much information about DC composition, phenotype and function in the human gut in CD. Methods Human intestinal resections were obtained from patients with ileocolonic CD and proximal colonic cancer. Both inflamed and non-inflamed tissue was obtained from the ileum and colon from CD patients. The non-affected tissue from the proximal (terminal ileum) and distal (proximal colon) sides of the colonic cancer resections (minimum 10cm distance from the tumor) constituted the reference tissue. Tissue was disaggregated and cDC and macrophages enriched by flow-sorting. Human intestinal cDC were identified within singlet viable leukocytes as CD14-CD64-HLA-DR+CD11c+. Type 1 cDC (cDC1) were defined as CD103+SIRPα- while type 2 cDC (cDC2) and identified as SIRPα+ and further divided into subsets based on the expression of CD103. Macrophages were identified within singlet viable leukocytes as CD14+CD64+HLA-DR+. All three cDC subsets and total macrophages were used to stimulate allogeneic CD4+ naïve T-cells which were further characterized by flow cytometry. Results All 3 human intestinal cDC subsets from non-CD controls were able to stimulate naïve T-cells as opposed to intestinal macrophages. Indeed, stimulated T-cells produced IL-10 and co-expressed FoxP3, being this capacity increased in both CD103+ subsets (CD103+SIRPα- and CD103+SIRPα+). Moreover, all three ileal cDC subsets stimulated T-cells more efficiently than their paired colonic counterparts, although the acquired T-cell profile did not differ among tissues. None of the cDC subets, on the contrary, induced the expression of IFNγ or IL-17 on stimulated T-cells. Referred to CD patients, all three colonic cDC subsets were more stimulatory than their counterparts from the control tissue, while CD103+SIRPα+ cDC from the inflamed ileum primed the generation of IL-17+ responding T-cells. Conclusion All human intestinal cDC subsets prime the generation of regulatory FoxP3+ and IL-10+ T-cells. This capacity was increased in both CD103+SIRPα- and CD103+SIRPα+, in agreement with the regulatory functions attributed to CD103+ cDC. All ileal cDC subsets were also more stimulatory than their colonic counterparts. Nevertheless, colonic cDC from CD patients were more stimulatory that non-CD controls, rendering CD103+SIRPα+ cDC from the inflamed tissue in CD with a higher capacity to generate Th17 cells, which suggests that their regulatory functions can be reshaped by the inflamed tissue microenvironment.

Background Ustekinumab (UST) is an effective therapy for induction and maintenance of remission in Crohn’s disease (CD). Intensification of UST maintenance dosage has shown effectiveness in some adult patients, but no similar data are available in children. The aim of the study was to evaluate the effectiveness and safety of dose escalation of UST in paediatric CD. Methods This was a retrospective multicenter study from 25 centers affiliated to the IBD Interest and Porto groups of ESPGHAN. We included children with CD who initiated UST at a standard dosing and subsequently underwent dose escalation to intervals shorter than 8 weeks, or re-induction due to active disease. Demographic, clinical, laboratory, endoscopic and imaging data were collected at escalation and during a 12 months follow-up. Clinical remission was defined as weighted Paediatric Crohn’s Disease Activity Index (wPCDAI)17.5 points. Adverse events were explicitly recorded. Results Sixty-nine children, with a median age of 15.8 (IQR 13.8–16.9) years and disease duration of 4.3 (2.9–6.3) years were included. Sixty-eight (98.6%) and 59 (86.8%) children were biologic and immunomodulators experienced, respectively. UST dose was escalated after a median of 6 (3.6–12) months of therapy. Clinical response and remission were observed in 46 (67%) and 29 (42%) children at 3 months, respectively. The strongest predictor of clinical remission was lower wPCDAI at escalation (p=0.001). The median serum levels of C-reactive protein decreased from 14 (3–28.03) to 5 (1.1–20.5) mg/L at 3 months (p=0.012), and fecal calprotectin from 1110 (499–2300) to 248 (118–1159) mcg/g at 12 months (p=0.05). Endoscopic and transmural healing were achieved in 3/19 (16%) and 2/15 (13%) patients, respectively, of those with available tests. Overall, 13 patients (19%) discontinued therapy due to active disease, at a median of 3 (3–4.5) months. No serious adverse events were reported. Conclusion Two-thirds of children with active CD achieved response following dose escalation of UST.

Background It has been reported that familial aggregation occurs in 10–20% of inflammatory bowel disease (IBD) patients1. Familial IBD has been associated with disease anticipation2 and with an increased need for immunosuppressants3 and surgery4. However, most studies were performed before the widespread use of biological agents and this may impact on the need for surgery. We aimed to compare the clinical outcomes of IBD (by means of the need for biological therapy and abdominal surgery) between familial and sporadic forms of IBD in the era of biological therapies. Methods Data were extracted from the ENEIDA registry by GETECCU, a Spanish, prospectively-maintained, IBD database in which more than 80 centers are participating. Only adult patients diagnosed with IBD since 2005 and prospectively followed in the registry since diagnosis were included. Familial IBD was defined as those cases with at least one first-degree relative diagnosed with IBD. Sporadic IBD was defined as those cases with no familial relative (of any degree) with IBD. Kaplan-Meier survival curves were performed to evaluate the cumulative probabilities of remaining biologic-free and surgery-free. Log-rank test was performed to compare them between familial and sporadic IBD forms. Chi-square test was performed for the rest of variables. Results A total of 5,263 patients (2,627 Crohn’s disease [CD]; 2,636 ulcerative colitis [UC]) were included. Of them, 507 (10%) were familial cases (274 CD, 233 UC; P=0.05). The median follow-up was 38,4 and 35.5 months, respectively (P=0.086). Familial cases were younger (P=0.022) and had a higher proportion of females among UC cases (P=0.048). No differences were observed in the need for biological therapy in both CD and UC between familial and sporadic IBD. Regarding surgery, no differences were observed in the cumulative probabilities of a first intestinal resection for CD and colectomy for UC. Similar results were obtained when all the analyses were restricted to those subgroups at high-risk for surgery (i.e. CD with ileal involvement and extensive UC). Conclusion In patients diagnosed with IBD in the era of biological therapies, familial forms have the same requirements for biological agents and resectional surgery as sporadic forms. Therefore, familial aggregation does not seem to be a factor for a more aggressive disease.

Herein, a straightforward approach for the controlled coating of gold microelectrodes with molecularly imprinted polymer (MIP) thin films is presented. To this end, a new iniferter has been synthesised, 3-mercaptopropyl diethylcarbamodithioate, which contains terminal thiol groups capable of forming self-assembled monolayers (SAM) on gold substrates. The iniferter SAM was activated under UV radiation after the immersion of the microelectrode in the polymerisation solution, containing 4-ethylphenol (4EP) as template and 4-vinylpyridine and ethylene dimethacrylate as functional monomer and cross-linker respectively. The voltammetric behaviour of the resulting MIP-coated microsensor was assessed next, finding that electrochemical response was linear to the concentration of the target analyte (4EP) in a range comprised between 10−6 and 10−3 mol L−1, showing a sensitivity of 1.02 ± 0.02 (nA L μmol−1) (R2: 0.9983). Measurement repeatability was also evaluated performing a series of measurements with the same sensor at two concentrations levels of 4EP, 5 × 10−6 mol L−1 and 10−4 mol L−1, obtaining relative standard deviations (RSD) of 3.41% and 1.92% respectively. Similarly, sensor-to-sensor repeatability was also determined obtaining RSD values of 10.02% and 16.97% respectively. Sensor selectivity was finally studied comparing the peak current intensity of 4EP with current intensities registered with structural analogues. It was found that sensor was capable of discriminating the target compound from structural analogues presenting remarkable selectivity, even for almost identical compounds such as 4-vinylphenol.

Chronic kidney disease (CKD) is a progressive pathological condition in which renal function deteriorates in time. The first diagnosis of CKD is often carried out in general care attention by general practitioners by means of serum creatinine (CNN) levels. However, it lacks sensitivity and thus, there is a need for new robust biomarkers to allow the detection of kidney damage particularly in early stages. Multivariate data analysis of plasma concentrations obtained from LC-QTOF targeted metabolomics method may reveal metabolites suspicious of being either up-regulated or down-regulated from urea cycle, arginine methylation and arginine-creatine metabolic pathways in CKD pediatrics and controls. The results show that citrulline (CIT), symmetric dimethylarginine (SDMA) and S-adenosylmethionine (SAM) are interesting biomarkers to support diagnosis by CNN: early CKD samples and controls were classified with an increase in classification accuracy of 18% when using these 4 metabolites compared to CNN alone. These metabolites together allow classification of the samples into a definite stage of the disease with an accuracy of 74%, being the 90% of the misclassifications one level above or below the CKD stage set by the nephrologists. Finally, sex-related, age-related and treatment-related effects were studied, to evaluate whether changes in metabolite concentration could be attributable to these factors, and to correct them in case a new equation is developed with these potential biomarkers for the diagnosis and monitoring of pediatric CKD.

[EN]Faecal matter is commonly recovered from archaeological sites related to human/animal activity. The identification of its source is essential to understand the domestication process and the relationship between humans and domestic animals in ancient times. Additionally, faecal matter is useful for determining the diet of animals. Therefore, the use of an appropriate biomarker is essential. The ratios of 5 beta-Stanols and bile acid biomarkers are most commonly used to identify the biogenic origin of faecal matter. However, other biomarkers such as archaeol can be a good proxy for ruminants. Conversely, plant-based diet of the animals can be discerned by analysis of faecal matter. n-Alkanes are the most common proxies of the animal diet, followed by long-chain fatty acids and long-chain alcohols, and the interest in the analysis of carbon isotopes has recently increased owing to the possibility of distinguishing animal diets. In this review, we describe the identification of faecal and diet biomarkers in animals. Ratios and proxies used in archaeological fields are also described and discussed to determine the best approach for accurate identification. This work was funded by the Basque Government, Research Groups of the Basque University System (Project No. IT1186-19) .

The work presented here explores the grafting of molecularly imprinted nanoparticles (MIN) on silica beads for the development of new chiral stationary phases (CSP). Both solid-phase imprinting and precipitation polymerisation were tested for MIN synthesis though the latter approach was the only one that provided efficient chiral selectors. MIN particles were prepared by iniferter polymerisation initiated by UV radiation, using itaconic acid as functional monomer and ethylene dimethacrylate as cross-linker. This resulted in particles with an average size of 249.0 ± 4.0 nm which were covalently immobilised onto chromatographic silica beads. The resultant CSP based on the composite silica beads-MIN was capable of resolving the racemate of the antidepressant drug citalopram and also separating its major metabolites by liquid chromatography, with better efficiency and peak symmetry than other MIP based CSP. The methodology presented here allowed for the quantification of the pharmacologically active enantiomer (+)-(S)-citalopram (SCIT) and its main metabolites (+)-(S)-desmethylcitalopram (SDCIT) and (+)-(S)-didesmethylcitalopram (SDDCIT) in urine, registering mean recoveries that ranged from 91.5 to 103.7% with RSD values that were below 10% in all tested concentration levels (0.1, 0.75 and 5 μg mL−1), which confirmed method suitability for the intended application.