OBJECTIVES:To compare a new ready-to-use monotest immunoassay, CHORUS Promonitor, for the quantification of serum biological drug levels and anti-drug antibodies of anti-TNF agents, against the reference batch-based ELISA test, Promonitor. METHODS:Blood samples were collected from patients treated with anti-TNF agents, infliximab (IFX) or adalimumab (ADL). IFX and ADL levels, as well as anti-IFX and anti-ADL antibodies were quantified and compared between the standard ELISA reference test, Promonitor, and the automated monotest ELISA assay, CHORUS Promonitor. Data analysis included both qualitative and quantitative comparison between both tests. For the qualitative comparison, overall percent agreement (OPA) was calculated. For the quantitative comparison, Passing-Bablok regression analysis and Bland-Altman analysis were used. RESULTS:For IFX and ADL levels, the qualitative overall agreement between methods was 100 % (Cohen's coefficient=1). For anti-IFX and anti-ADL antibodies, OPA was 98.8 % and 97.3 %, respectively. Quantitative comparison indicated a very strong correlation between both assays: IFX (r=0.97, n=74), ADL (r=0.95, n=54), anti-IFX (r=0.93, n=72), and anti-ADL (r=0.97, n=61). The regression analysis determined an excellent comparability of drug levels between methods. Bland-Altman analysis showed a bias difference between assays of 6 % for IFX, 0 % for ADL, 24 % for anti-IFX, and 14 % for anti-ADL. CONCLUSIONS:Monotest CHORUS Promonitor was a reliable assay to quantify IFX, ADL, anti-IFX and anti-ADL in samples with comparable results to those obtained with the reference batch-based ELISA technique.

Background Although the serum levels of infliximab (IFX) and adalimumab (ADA) are correlated with the clinical response in patients with inflammatory bowel disease (IBD), the optimal management strategy during maintenance therapy remains controversial. We performed a randomized trial to determine whether proactive monitoring drug in patients with inflammatory bowel disease is better than control clinical to keep clinical remission Methods We conducted a randomized, prospective, multicenter trial involving 209 patients with Crohn's disease (CD) or ulcerative colitis (UC) who had been in clinical remission for at least 12 weeks. Patients were randomized into two groups: 104 in the TDM group and 105 in the clinical practice (CP) group. In the TDM group, the dosing and intervals of IFX and ADA were adjusted at each visit to maintain optimal serum concentrations (3–7 μg/mL for IFX and 5–8 μg/mL for ADA). The primary endpoint was the proportion of patients who remained in clinical remission at 12 months of follow-up. The secondary endpoints included the number of disease flares, duration of clinical remission, rate of hospital admissions related to IBD, and quality of life. Results The primary endpoint of remission was achieved in 94 patients (90.3%) in the TDM group and 86 patients (81.9%) in the CP group, with a difference of 8.4% between the groups (p = 0.079; 95% CI: –17.70.91). The mean duration of remission over the 12-month follow-up was significantly longer in the TDM group [48.04 ± 10.76 weeks] than in the CP group [45.69 ± 14.21 weeks] (p = 0.03). The number of disease flares was lower in the TDM group (15 flares) than inthe CP group (24 flares). At baseline, optimal IFX levels were present in 51 patients (48.5%), and optimal ADA levels were present in 36 patients (35.3%). Conclusions In this prospective randomized trial of patients with CD or UC in clinical remission receiving IFX or ADA, compared withstandard clinical management, proactive TDM did not significantly increase the overall remission rate at one year. However, patients in the TDM group remained in clinical remission for a significantly longer duration. ClinicalTrials.gov Identifier: NCT06666569. (30 oct 2024). Retrospectively registered.

ObjetivoNo está claro si la elevación de ácido úrico sérico (AUS) preoperatorio puede desempeñar un papel en el desarrollo de daño renal agudo (DRA) asociado a cirugía cardiaca (DRA-CS). Se realizó un estudio de cohortes para evaluar la influencia de la hiperuricemia en el DRA en pacientes de alto riesgo para desarrollar DRA-CS.DiseñoEstudio de cohortes prospectivo multicéntrico.EntornoCatorce hospitales universitarios en España y en Reino Unido.ParticipantesSe estudiaron a 261 pacientes consecutivos con alto riesgo de desarrollar DRA-CS, según una puntuación de Cleveland ≥4 puntos, de julio a diciembre de 2017.IntervencionesNinguna.Mediciones y resultados principalesSe utilizaron los criterios AKIN para la definición de DRA. Para determinar la asociación ajustada entre hiperuricemia (>=7mg/dL) e DRA se utilizaron modelos de regresión logística multivariable y análisis de pares emparejados por puntuaje de propensión.El AUS preoperatorio elevado (>=7mg/dL) estaba presente en 190 pacientes (72,8%), mientras que la DRA-CS se produjo en 145 pacientes (55,5%). En los modelos de regresión logística multivariable, la hiperuricemia no se asoció con un aumento significativo del riesgo de DRA (Odds Ratio [OR] ajustado: 1,58; intervalo de confianza [IC] 95%: 0,81-3; p=0,17). En el análisis de emparejamiento por puntaje de propensión de 140 pacientes, el grupo de hiperuricemia experimentó probabilidades ajustadas similares de DRA (OR 1,05; IC 95%: 0,93-1,19; p=0,37).ConclusionesLa hiperuricemia no se asoció con un mayor riesgo de DRA en esta cohorte de pacientes con alto riesgo de desarrollar DRA-CS.

Abstract Background Although it is known that the levels of infliximab or adalimumab are correlated with clinical response, there is controversy about the best strategy to follow in patients with Inflammatory Bowel Disease (IBD) in remission and undergoing maintenance treatment. Methods We conducted a randomized, prospective, single-blinded, and multicentre trial in patients with Crohn’s Disease (CD) or Ulcerative Colitis (UC) who have remained in clinical remission for at least 12 weeks and are receiving adalimumab (ADA) or infliximab (IFX) as maintenance treatment. Patients were assigned to two groups. In the first group, patient management was done considering therapeutic drug monitoring (TDM). In the second, according to usual clinical practice (CP). The optimal serum range was within 3-7µg/ml and 5-8µg/ml for IFX and ADA respectively, based on the use of Promonitor-IFX, and Promonitor-ADL kits. The primary endpoint was to maintain patients in clinical remission (target >16% between both groups at 12 months) and diminish the frequency of flare-ups. Results In total, 209 patients were randomized, 29 UC (27.6%), 76 CD (72.4%) as the clinical practice group, and 24 UC (23.1%), 80 CD (76.9%) as the drug monitoring therapeutic group. Infliximab was administered in 105 patients and adalimumab in 104. Remission at the end of the study was achieved in 98.1% of the proactive dosing group and 90.5% of the clinical practice group (p=0.02), with a difference between both groups of 7.6%. The number of flare-ups was 1.3/10 patient-years in the TDM group and 2.4/10 patient-years in the CP group. The IRR of flare-up throughout the study was 0.71 (95% CI 0.32 – 1.55). In the group with IFX: IRR = 0.56 (95% CI 0.08 – 3.81) and with ADA: 0.78 (95% CI 0.29-2.16). The changes made in the drug dose are shown in Table 1. Conclusion Differences were found in favour of the TDM group, with increasing remission rates (7.6%) and half number of flare-ups. However, the pre-established effectiveness remission target (16%) was not met. In the subgroup of patients with Infliximab, management through TDM seems to have an advantage over usual clinical control.

Purpose: It is unclear whether preoperative serum uric acid (SUA) elevation may play a role in the development of acute kidney injury (AKI) associated with cardiac surgery (CSA-AKI). We conducted a cohort study to evaluate the influence of preoperative hyperuricemia on AKI in patients at high risk for developing SC-AKI. Design: Multicenter prospective international cohort study. Setting: Fourteen university hospitals in Spain and the United Kingdom. Participants: We studied 261 consecutive patients at high risk of developing CSA-AKI, according to a Cleveland score >4 points, from July to December 2017. Interventions: None. Measurements and Main Results: AKIN criteria were used for the definition of AKI. Multivariable logistic regression models and propensity score-matched pairwise analysis were used to determine the adjusted association between preoperative hyperuricemia (> = 7 mg/dL) and AKI. Elevated preoperative AUS (> = 7 mg/dL) was present in 190 patients (72.8%), whereas CSA-AKI occurred in 145 patients (55.5%). In multivariable logistic regression models, hyperuricemia was not associated with a significantly increased risk of AKI (adjusted Odds Ratio [OR]: 1.58; 95% confidence interval [CI]: 0.81-3; p = 0.17). In propensity score-matched analysis of 140 patients, the hyperuricemia group experienced similar adjusted odds of AKI (OR 1.05, 95% CI 0.93-1.19, p = 0.37). Conclusions: Hyperuricemia was not associated with an increased risk of AKI in this cohort of patients undergoing cardiac surgery at high risk of developing CSA-AKI. (c) 2024 The Author(s). Published by Elsevier Espania, S.L.U. on behalf of Sociedad Espaniola de Anestesiologia, Reanimacion y Terapeutica del Dolor. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

Background: Data regarding multiple switches including reverse switching between infliximab and its biosimilars are scarce in the field of inflammatory bowel diseases (IBD). Objectives: We investigated the clinical effectiveness as primary outcome measure after repeated switches. Secondary endpoints included C-reactive protein (CRP) levels, immunogenicity (trough levels (TL); anti-drug antibodies (ADA), safety and drug persistence. Design: This study is a prospective, single-centre, observational cohort study. IBD patients receiving originator infliximab were switched to biosimilar SB2 and then reverse switched after 96weeks and followed up for another 48weeks. Methods: Clinical disease activity (Harvey-Bradshaw-index (HBI) in Crohn's disease (CD), partial Mayo score (pMS) in ulcerative colitis (UC)), CRP, TL, ADA, therapy-discontinuations and (serious) adverse events ((S)AE)) were monitored throughout the study. Results: Ninety-five patients (60 CD, 38 female) were enrolled. The median HBI was 2 (interquartile range (IQR) 1-4) at baseline and 2 (1-4) at week 48, resulting in a mean intra-individual change of 0.0 (standard deviation (SD) 1.5). The median pMS was 1 (IQR 0-1) at baseline and 0.5 (0-1) at week 48 resulting in a mean intra-individual change of 0.0 (SD 0.8). Clinical remission was achieved in 80% at baseline and 82% at week 48. Median CRP 2.0mg/l (IQR 1.0-4.1) at baseline and 2.4mg/l (1.1-5.2) at week 48 resulted in a mean change of 1.7 (SD 5.8) and no significant differences in CD (p=0.3) and UC (p=0.9). Median TL were 7.2 mu g/ml (IQR 3.8-19.3) at baseline and 5.5 mu g/ml (3.5-13.1) at week 48, resulting in a mean change of -1.0 (SD 7.4) with no statistical significance (CD p=0.26, UC p=0.41). De-novo-ADA were developed by 3.4%. The discontinuation rate was 14.7%. Safety signals were consistent with previous studies. Conclusion: Reverse switching had no impact on efficacy of infliximab therapy in our cohort of IBD patients. The switch didn't influence immunogenicity or safety of therapy.

Background Promonitor Quick IFX is a lateral flow test (LFT) for the quantification of infliximab (IFX) in human whole blood (finger prick or venous) or serum in 20 minutes. This LFT is based on a sandwich immunoassay to quantify either the reference IFX or biosimilars. Objectives The objective of this study was to perform the required analytical studies to establish the specifications of the product. Methods Clinical and Laboratory Standards Institute (CLSI) guidelines were followed for the evaluation of the analytical specifications of the LFT in whole blood and serum matrices: Linearity (EP-06-A), Detection capability (EP17-A2), Interfering substances (EP07, 3rd Edition) and Intermediate precision (EP05-A3). Results were obtained in combination with the automated portable reader PQreader. A Datamatrix provided with each Promonitor Quick IFX kit contains the calibration information required for the PQreader to measure the Control and Test lines and report the IFX concentration. Results The linear assay range was determined to be 1-58 µg/mL in whole-blood and 0.6-67 µg/mL in serum according to the processes indicated in the Package Insert. The Limit of Blank is 0.8 μg/mL, the Limit of Detection and Lower Limit of Quantification (LLoQ) are 1.1 μg/mL, and the Upper Limit of Quantification (ULoQ) is 15.4 μg/mL. There was no effect on assay performance when each of the following substances were added to samples with 0, 3, and 7 μg/mL of IFX: Haemoglobin (>1000 mg/dL), Bilirubin (>40 mg/dL), Triglycerides (>1500 mg/dL), HAMA (160 AU/mL), Rheumatoid factor (200 IU/mL), EDTA (5.4 mg/mL), Heparin (51 U/mL), Citrate (11.4%), Vedolizumab (60 μg/mL) and Adalimumab (20.25 μg/mL). Repeatability and within-device precision results obtained for the positive samples are shown in Table 1. Table 1. IFX theoretical concentration (μg/mL) Whole blood samples Serum samples Mean observed IFX concentration (μg/mL) Repeatability Within-device precision Mean observed IFX concentration (μg/mL) Repeatability Within-device precision SD CV% SD CV% SD CV% SD CV% 3 3.2 0.6 18 0.8 25 3.6 0.5 15 0.6 17 7 7 1.3 18 1.7 24 8.3 1.4 16 1.8 21 10 9.8 1.8 18 2.7 28 10.9 1.8 16 2.3 21 The negative samples showed a negative result in all the measurements. Conclusion Promonitor Quick IFX is the first LFT available for true Point of Care testing of patients treated with IFX with just a finger prick sample. It provides quick turnaround time to facilitate therapeutic drug monitoring and aid immediate decision making in the doctor office or hospitals with an excellent analytical performance. Disclosure of Interests Amagoia Ametzazurra Employee of: Employee of Progenika Biopharma - Grifols, Javier Pascual Employee of: Employee of Progenika Biopharma - Grifols, Lorena Del Rio Employee of: Employee of Progenika Biopharma - Grifols, Ainara Maguregui Employee of: Employee of Progenika Biopharma - Grifols, Daniel Nagore Employee of: Employee of Progenika Biopharma - Grifols, M. Begoña Ruiz-Argüello Employee of: Employee of Progenika Biopharma - Grifols

BackgroundPromonitor Quick IFX and Promonitor Quick ADL are rapid point of care lateral flow tests (LFT) based on a sandwich immunoassay for the quantification of infliximab (IFX) and adalimumab (ADL), respectively, in human whole blood (finger prick or venous) or serum. These tests are to be used as an aid in Therapeutic Drug Monitoring (TDM) of rheumatic and inflammatory bowel disease patients under anti-TNFα therapy. The international standards (IS) developed by World Health Organization (WHO) for IFX and ADL allow harmonization and comparability among different assays.ObjectivesThe aim of this study, was to show that Promonitor Quick IFX and Promonitor Quick ADL can measure either reference or biosimilar drugs, as well as to evaluate the agreement of Promonitor Quick IFX and Promonitor Quick ADL tests and the WHO IS.MethodsClinical and Laboratory Standards Institute EP10-A3 guidelines were followed to estimate the bias of Promonitor Quick assays when used to quantify IFX or ADL in samples containing the reference drugs, biosimilars or the WHO IS. Briefly, whole blood was spiked with four known concentrations of IFX or ADL, including current clinical decision levels. Ten replicates were measured of each level along two days.Promonitor Quick IFX was evaluated using the reference drug, SB2 and CT-P13 biosimilars, and the WHO IS (NIBSC 16/170).Promonitor Quick ADL was evaluated using the reference drug, ABP501 and SB5 biosimilars, and the WHO IS (NIBSC 17/236).Results were obtained in combination with the automated portable reader PQreader.ResultsBias was estimated by comparing the observed concentration of drug spiked whole blood samples. Each biosimilar was compared to the reference at the different drug levels tested. Results showed that Promonitor Quick IFX and Promonitor Quick ADL are able to measure equivalently any molecule (see Table 1).Table 1.Promonitor Quick IFX bias results in whole blood samples. Each molecule was compared to the reference drug.IFX concentration (μg/mL)Bias (%)CT-P13SB2GP1111WHO IS314%3%4%8%79%0%5%15%101%5%6%8%Promonitor Quick ADL bias results in whole blood samples.Each molecule was compared to the reference drug.ADL concentration (μg/mL)Bias (%)ABP501SB5WHO IS317%2%3%513%3%12%82%2%7%10517%2%Similar results were obtained when serum matrix was used.The accuracy or closeness of the agreement between the result provided by Promonitor Quick IFX and Promonitor Quick ADL and the true value of the measurand was assessed by measuring the IS developed by the WHO (see Table 1).ConclusionPromonitor Quick IFX and Promonitor Quick ADL allow monitoring of patients treated with IFX and ADL, respectively, with just a finger prick sample. Both tests can quantify reference and biosimilar drugs with equivalent results. Moreover, comparable results were obtained with the WHO IS, and thus, demonstrate that Promonitor Quick tests are suited to accurately determine drug levels at the clinical decision points in both whole blood and serum, proving to be an effective and valuable tool in TDM and immediate decision making in the doctor office or hospitals.Disclosure of InterestsAmagoia Ametzazurra Employee of: Employee of Progenika Biopharma - Grifols, Javier Pascual Employee of: Employee of Progenika Biopharma - Grifols, Lorena Del Rio Employee of: Employee of Progenika Biopharma - Grifols, Ane Urigoitia Employee of: Employee of Progenika Biopharma - Grifols, Daniel Nagore Employee of: Employee of Progenika Biopharma - Grifols, M. Begoña Ruiz-Argüello Employee of: Employee of Progenika Biopharma - Grifols

Background Despite numerous studies, Therapeutic Drug Monitoring (TDM) of biological therapies is still debated partly motivated by the accessibility to a ready-to-use monotest device capable of delivering accurate results in a timely manner without the burden of sample batching, therefore allowing immediate decision making. Objectives We aimed at comparing the new Chorus Promonitor Adalimumab monotest running in the fully automated random-access Chorus TRIO system to the reference ELISA test Promonitor ADL run in a Triturus system. Methods Chorus Promonitor Adalimumab (Diesse Diagnostica Danese, Italy) is an immunoassay kit for the automated quantitative detection of adalimumab (ADL) in human serum using a ready-to-use disposable monotest device applied on the Chorus TRIO (Diesse Diagnostica Danese, Italy) instrument, a random-access single test multiparametric system for immuno-colorimetric assays. The new device implements the same specific reagents as in the reference ELISA test Promonitor ADL (Progenika, Spain) run in a Triturus (Grifols, Spain) system, therefore ensuring the same analytical specificity and applicability for patient monitoring previously demonstrated with the predicate ELISA. The new monotest device contains all the reagents necessary to perform the assay, and a lot-specific master curve method is used for calibrating. The comparison was performed in a set of 53 serum samples from patients under ADL therapy that covered the entire drug trough concentrations found in clinical practice (up to 30 ug/mL). Pearson’s correlation, Bland-Altman and Passing-Bablok regression analysis were used to study the association and quantitative comparison between the methods. Results Time to first result for the Chorus Promonitor Adalimumab test was 2 hours and 45 min minutes and after this a new result was delivered every 30 seconds. Positive and negative percent agreements between both tests were 100%. A high correlation between both tests was found (coefficient of correlation of 0.959, p<0.01). The Passing-Bablok regression analysis determined an excellent comparability of both data sets with a slope of 1.032 (0.952-1.129) with an intercept of -0.428 (-1.292-0.053). Figure 1. Conclusion The Chorus Promonitor Adalimumab represents the first evolution of the gold-standard Promonitor ELISA technology into a monotest random-access technology that enables quick turnaround time to facilitate TDM for ADL and aid immediate decision making. Disclosure of Interests None declared

Cardiac ultrasound has become an essential tool for diagnosis and hemodynamic monitoring in critically ill patients. Scientific societies need to work toward developing a training program that will allow clinicians to acquire competence in performing cardiac ultrasound and understanding its indications. The Clinical Ultrasound for Intensive Care task force of the Spanish Society of Anesthesiology and Critical Care (SEDAR) and the Spanish Society of Emergency Medicine (SEMES) have drawn up this position statement defining the learning objectives and training required to acquire the competencies recommended for basic ultrasound management in the intensive care and emergency setting in order to obtain a diploma in Basic Ultrasound in Intensive Care and Emergency Medicine. This document defines the training program and the competencies needed for basic skills in ultrasound in Intensive Care and Emergency Medicine-part of the Diploma in Ultrasound for Intensive Care and Emergency Medicine awarded by SEDAR/SEMES. The Spanish Society of Anesthesia (SEDAR), Spanish Society of Internal Medicine (SEMI) and Spanish Society of Emergency Medicine (SEMES) have drawn up a position statement determining the competencies and training program for a diploma in ultrasound (lung, abdominal and vascular) in Intensive Care and Emergency Medicine. To obtain the SEDAR/SEMES Diploma in Ultrasound in Intensive Care and Emergency Medicine, clinicians must have completed the SEDAR, SEMI and SEMES Diploma in basic ultrasound and the Diploma in lung, abdominal, and vascular ultrasound.

The goal of this study was to validate the use of capillary blood in a real point-of-care (POC) setting for patients under infliximab treatment by using Promonitor Quick lateral flow (LF) tests. Results were compared to the Promonitor ELISA reference technique in serum samples used by centralised laboratories. A prospective, observational study was designed to evaluate the performance of a rapid LF test (Promonitor Quick IFX, Progenika, Spain). 160 infliximab treated rheumatology consecutive patients (400 samples) were recruited in two hospitals in Galicia, Spain. Prior to the infusion, a finger prick sample was obtained and analysed. Anti-infliximab antibodies were also determined with Promonitor Quick ANTI-IFX1-4. Results were read with the automated portable PQreader instrument. Additionally, a serum sample was collected for subsequent comparative analysis with either LF or ELISA tests. Qualitative (positive (PPA) and negative (NPA) agreements) and quantitative (Pearson correlation and bias) performance of the LF test was compared to ELISA, as well as between different specimens following CLSI EP09-A3. Overall agreement between Promonitor Quick IFX finger prick and ELISA test was 91% (88% PPA; 100% NPA). The quantitative comparison showed a good correlation (Pearson correlation coefficient: 0.85 and observed bias: 25%) (Table 1). Similar results were also observed when serum was used with either the LF or the ELISA tests (98% overall agreement, 0.91 correlation coefficient; 6% bias) (Table 1). Overall agreements for visual and automated (PQreader) interpretations with Promonitor Quick ANTI-IFX were 99% and 100% for finger prick and serum specimens, respectively (Table 2). Promonitor Quick can be used to reliably quantify infliximab in capillary blood samples and results are comparable to those obtained with the reference ELISA technique. The use of the rapid POC test with finger prick will allow clinicians to monitor their patients in a fully decentralized mode to aid in the decision making process. PQreader is a sensitive portable equipment to report drug as well as antibody levels in the patient samples.

To assess the clinical and cost-effectiveness of therapeutic drug monitoring (TDM) based on serum adalimumab levels compared to standard of care in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. This was a non-inferiority, multicentric, non-randomized, pragmatic trial including adult patients diagnosed with moderate-to-severe, clinically stable rheumatic diseases treated with adalimumab. Consecutive patients were assigned 1:2 to the control (CG) or the intervention group (IG), based on the site of inclusion, and followed up for 18 months. Adalimumab serum levels were measured at each study visit and released to the IG only to modify dosing strategy. Data on disease activity, healthcare resource utilization and health-related quality of life (HRQoL) measured through the EQ-5D-5L were collected. Number of persistent and overall flares, time to first flare, days experiencing high disease activity, total direct costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated. Of the 169 recruited patients, 150 were included in the analysis (52 and 98 patients in the CG and IG, respectively). The primary endpoint was not met as persistent flares were not significantly lower in the IG, although mean (SD) number of flares was numerically lower in the IG (0.67 [0.70] versus 0.90 [0.82], P = 0.073), respectively. Based on EQ-5D-5L utilities, HRQoL was significantly higher in the IG at 3 (P = 0.001) and 6 months (P = 0.035), which overall translated into 0.075 QALYs gained per patient for the IG at month 18. Overall, direct costs were significantly lower for the IG patients (€15,311.59 [4,870.04] versus €17,378.46 [6,556.51], P = 0.030), resulting in the intervention being dominant, leading to increased QALY at a lower overall cost Adalimumab dose tapering based on TDM for rheumatic patients led to an increased quality of life and QALY gain and entailed lower costs, being a more cost-effective alternative than clinically guided management.

A prospective, observational cohort study was conducted in Crohn ́s disease (CD) patients treated with ustekinumab (UTK). Trough UTK and anti-UTK antibody levels were measured with Promonitor®-UTK and Promonitor® Anti-UTK tests (Progenika, Spain), respectively and compared to the corresponding results using LISA TRACKER Ustekinumab DUO (LTU) (Theradiag, France) in 100 serum samples collected at baseline and during the course of UTK treatment. Qualitative and quantitative analysis comparison of the two tests was done using descriptive statistics, Pearson Correlation, Passing-Bablok regression and Bland-Altman analysis. Both assays correlated and can be used for monitoring of UTK levels, however the measurement range and the sample dilution recommended by Promonitor-UTK covers more accurately the UTK concentrations found in CD patients, whereas use of the LTU forces the user to repeat the testing or perform two sample dilutions by default because the recommended sample dilution is not appropriate for the population. In the absence of a gold standard method to unequivocally assess tests accuracy, UTK concentration results measured with different tests should be taken into account with caution and it is advised that monitoring drug concentrations in patients over time would be best done using the same test system.

Background: Long-term data on inflammatory bowel disease (IBD) patients switched from originator to biosimilar infliximab SB2 are lacking. The aim of the conducted study was to investigate the effectiveness, immunogenicity and safety of a large prospectively followed-up IBD patient cohort that was entirely switched from originator infliximab to biosimilar SB2 treatment. Methods: This was a prospective, single-center, longitudinal, observational study describing clinical outcomes in IBD patients, over an 80-week period following switch from originator infliximab to SB2. Primary outcome measures were change of disease activity [Harvey-Bradshaw Index for Crohn’s disease (CD), partial Mayo Score for ulcerative colitis (UC)], C-reactive protein (CRP), infliximab trough levels (TLs), anti-drug antibodies (ADAs) and adverse events. Results: One hundred and forty-four IBD patients (94 CD, 50 UC), with median duration of 30.5 months’ (range 2–110) treatment with originator infliximab were evaluated. Mean change of disease activity compared with baseline was −0.9 (SD 2.6), –0.4 (2.2) and –0.4 (2.0) in CD; 0.1 (1.1), 0.1 (1.1) and 0.1 (1.3) in UC patients at weeks 24, 48 and 72. Median infliximab TLs were 6.2 µg/ml (interquartile range 2.3–12.2), 5.0 µg/ml (2.7–10.0), 6.6 µg/ml (3.5–12.4) and 5.1 µg/ml (2.7–10.9) at baseline and weeks 24, 48 and 72. Median CRP levels were within normal ranges throughout the study. After the switch, 9.8% of the patients developed new ADAs. Persistence on SB2 was 90% (95% confidence interval 0.85–0.95), 79% (0.72–0.86), 72% (0.64–0.80) at weeks 26, 52 and 78. Serious adverse events occurred in 11 patients. Conclusion: Over the individual patient follow-up of 80 weeks, switch to biosimilar SB2 from originator infliximab does not result in increased disease activity or changed immunogenicity patterns. The switch to SB2 was well tolerated.

The use of ultrasound as a clinical diagnostic tool and guide of bedside procedures has become an indispensable examination in the acute critically ill patient. The training of professionals in minimum skills of knowledge, management and indications of use of ultrasound required to be defined by the Scientific Societies. The Intensive Care Ultrasound Working Group of the Spanish Society of Anesthesiology and Resuscitation (SEDAR), of the Spanish Society of Internal Medicine (SEMI) and the Spanish Society of Emergency Medicine (SEMES) has developed this consensus document in which the recommended training program and the minimum cornpetencies to be achieved with regard to the use of Ultrasound in Intensive Care, Anesthesia and Emergency medicine are defined. This document defines the training program and the skills to acquire in order to achieve the diploma in lung, abdominal and vascular ultrasound. This document can serve as a guide to define the skills to be acquired in the training programs of residents (MIRs) of specialists working in intensive care, anesthesia, and emergency medicine. (C) 2020 Sociedad Espanola de Anestesiologia, Reanimacion y Terapeutica del Dolor. Published by Elsevier Espana, S.L.U. All rights reserved.

The therapeutic management of patients with severe steroid-refractory ulcerative colitis still represents a critical clinical challenge. In this setting, cyclosporin is an effective and rapidly acting induction treatment that is applied in combination with maintenance therapeutic agents like thiopurines or vedolizumab. Here, we present the case of a 33-year-old ulcerative colitis patient with severe steroid-refractory ulcerative colitis who refused surgical intervention and previously demonstrated no long-term benefit to anti-TNF antibody, vedolizumab, cyclosporin, thiopurines or tofacitinib treatment. Intravenous cyclosporin therapy was re-initiated in the patient and, after signs of clinical response, therapy with ustekinumab was additionally applied. After 11 weeks of well tolerated cyclosporin and ustekinumab combination therapy, cyclosporin was discontinued upon clinical and endoscopic remission. Subsequently, ustekinumab treatment has been effective in maintaining remission during the follow-up period of 195 days.

Ganzleben, Ingo MD1,2; Hirschmann, Simon MD1,2; Köhler, Julia MD3; Fuchs, Florian S. MD1,2; Rieker, Ralf J. MD4; Baer, Eva MD1,2; Klenske, Entcho MD1,2; Nagore, Daniel PhD5; Neurath, Markus F. MD, PhD1,2; Atreya, Raja MD1,2 Author Information

El uso de la ecocardiografía a pie de cama se ha convertido en una herramienta indispensable en la monitorización hemodinámica y diagnóstico en el paciente crítico. Su conocimiento, manejo e indicaciones requieren por parte de las sociedades científicas una implicación para una formación reglada que capacite al profesional. El grupo de trabajo de Ecografía Clínica en Cuidados Intensivos de la Sociedad Española de Anestesiología y Reanimación (SEDAR) y el grupo de trabajo de Ecografía Clínica de la Sociedad Española de Medicina de Urgencias y Emergencias (SEMES) han desarrollado un documento de consenso en el que se definen los objetivos de aprendizaje y los requisitos necesarios para adquirir las competencias recomendadas en relación con el uso de la Ecocardiografía básica en Cuidados Intensivos y Urgencias, y así poder obtener un diploma acreditativo en Ecocardiografía básica en Cuidados Intensivos y Urgencias. En este documento se definen las competencias y el programa de formación para alcanzar el nivel básico en Ecocardiografía en Cuidados Intensivos y Urgencias, como parte del Diploma Completo en Ecografía en Cuidados Intensivos y Urgencias de la SEDAR y SEMES.La Sociedad Española de Anestesiología y Reanimación (SEDAR), junto con la Sociedad Española de Medicina Interna (SEMI) y la Sociedad Española de Medicina de Urgencias y Emergencias (SEMES), ha desarrollado un documento de consenso determinando las competencias y un programa formativo para la adquisición de un diploma en ecografía (pulmonar, vascular y abdominal) en Cuidados Intensivos y Urgencias. Solo cuando se obtenga el Diploma en Ecocardiografía básica y el Diploma en Ecografía pulmonar, vascular, abdominal de la SEDAR, SEMI y SEMES se podrá adquirir el Diploma Completo de Ecografía en Cuidados Intensivos y Urgencias de la SEDAR y SEMES.

BackgroundValidation of therapeutic drug monitoring (TDM) tests is an essential requirement for using these tools to help assess reasons for non-response. The arrival of biosimilars has prompted a need to validate that existing TDM tests are suitable to determine drug levels for all versions of a given molecule. The adalimumab (ADL) biosimilar SB5 (Biogen) was authorised by the European Commission in August 2017, and has recently become available for prescription in several European countries. Promonitor-ADL test is routinely used to monitor IBD patients treated with ADL.ObjectivesIn this study we validated the suitability and performance of Promonitor-ADL CE-marked TDM test for quantifying SB5 serum concentrations in comparison to reference adalimumab (Abbvie).MethodsThe study evaluated imprecision and bias applied to the reference ADL and SB5 biosimilar. The validation study was in line with the design requirements established in the Clinical & Laboratory Standards Institute (CLSI) guideline EP10-A3 for the determination of imprecision and bias. Imprecision was evaluated using three replicates of five human serum sample matrices representative of clinically relevant ADL concentrations and spanning the measurement range of Promonitor-ADL.1 Validations were ran on one instrument with one kit lot by one operator over six non-consecutive operating days and one run per testing day, with an acceptance criterium of CV%=20%. The Lower Limit of Quantification (LLOQ) of Promonitor-ADL was determined according to CLSI guideline EP17-A2.ResultsThe imprecision of Promonitor-ADL was calculated by estimating the components of variance due to within-run and between-day factors meet the accuracy goals proposed at all concentration levels of SB5 vs the reference adalimumab (CV% between 5% and 12%). The assessment of accuracy showed that Promonitor-ADL equally measures the active moiety of the reference adalimumab or the adalimumab biosimilar SB5. The test is able to quantify SB5 in the measurement range of 0.9 to 10.9 mg/mL with a bias estimate of -0.124 (1%) to 0.897 (10%) mg/mL and an overall imprecision of 5% to 11%. The measurement range includes the recommended clinical decision points. LLOQ of the test to determine ADL was determined to be 0.36 mg/mL.ConclusionThis study demonstrates that Promonitor-ADL test can measure either the reference ADL drug or the adalimumab biosimilar SB5 with equivalent sensitivity, precision and accuracy.References[1] Feuerstein, et al 2017. Gastroenterology 153: 827–834 AGA Institute Guideline on Therapeutic Drug Monitoring in IBD.Disclosure of InterestsM. Begoña Ruiz-Argüello Employee of: Progenika Biopharma - Grifols employee, Ainara Maguregui Employee of: Progenika Biopharma - Grifols employee, Antonio Martínez Employee of: Progenika Biopharma - Grifols employee, Daniel Nagore Employee of: Progenika Biopharma - Grifols employee

Validation of therapeutic drug monitoring (TDM) tests is an essential requirement for using these tools to help assess reasons for non-response. The arrival of biosimilars has prompted a need to validate that existing TDM tests are suitable to determine drug levels for all versions of a given molecule. The adalimumab (ADL) biosimilar SB5 (IMRALDI®, Biogen) was authorised by the European Commission in August 2017, and has recently become available for prescription in several European countries. Promonitor®-ADL test is routinely used to monitor IBD patients treated with ADL. In this study, we validated the suitability and performance of Promonitor-ADL CE-marked TDM test for quantifying SB5 serum concentrations in comparison to reference adalimumab (HUMIRA®, Abbvie). The study evaluated imprecision and bias applied to the reference ADL and SB5 biosimilar. The validation study was in line with the design requirements established in the Clinical and Laboratory Standards Institute (CLSI) guideline EP10-A3 for the determination of imprecision and bias. Imprecision was evaluated using three replicates of five human serum sample matrices representative of clinically relevant ADL concentrations and spanning the measurement range of Promonitor-ADL.1 Validations were ran on one instrument with one kit lot by one operator over six non-consecutive operating days and one run per testing day, with an acceptance criterium of CV% ≤20%. The Lower Limit of Quantification (LLOQ) of Promonitor-ADL was determined according to CLSI guideline EP17-A2. The imprecision of Promonitor-ADL was calculated by estimating the components of variance due to within-run and between-day factors meet the accuracy goals proposed at all concentration levels of SB5 vs. HUMIRA (CV% between 5% and 12%). The assessment of accuracy showed that Promonitor-ADL equally measures the active moiety of HUMIRA or SB5. The test is able to quantify SB5 in the measurement range of 0.9 to 10.9 μg/ml with a bias estimate of −0.124 (1%) to 0.897 (10%) μg/ml and an overall imprecision of 5% to 11%. The measurement range includes the recommended clinical decision points. LLOQ of the test to determine ADL was determined to be 0.36 μg/ml. This study demonstrates that Promonitor-ADL test can measure either the reference ADL drug or the biosimilar SB5 (IMRALDI) with equivalent sensitivity, precision and accuracy. Reference 1. Feuerstein JD, Nguyen GC, Kupfer SS, et al. American Gastroenterological Association Institute guideline on therapeutic drug monitoring in inflammatory bowel disease. Gastroenterology 2017;153:827–34.