Hospital Clinic Barcelona Research Articles

Abstract PO4-14-09: A computational model of the mechanisms of action of combined endocrine therapy and CDK4/6 inhibition predicts outcome in patients with Luminal B breast cancer

Abstract Background: Hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer (BC) is clinically and biologically heterogeneous. CDK4/6 inhibitors (CDK4/6i) are proven to be effective in different molecular subtypes of HR+/HER2- BC, including the PAM50 luminal B. However, not all patients benefit to the same extent and new biomarkers for response are needed. The aim of this study was to develop a computational workflow to predict the response of patients with luminal B BC to treatment with CDK4/6i in combination with endocrine therapy (ET). Methods: The main part of the workflow is a computational model representing the mechanisms of action of the drugs and their influence on protein signaling and cell proliferation in the tumor. The model was trained on publicly available data from BC cell lines (Western blot time courses and viability dose-response data). The model was then used to predict response in patients by incorporating gene expression profiles obtained at baseline. The output of the model was a score indicating how strongly the tumor responded to the treatment. Gene expression data determined using the nCounter BC360 panel was available at baseline from two patient cohorts: 1) the CORALLEEN phase II trial which evaluated neoadjuvant ribociclib plus letrozole vs multi-agent chemotherapy in postmenopausal patients with luminal B by PAM50, HR+/HER2- early BC (Prat et al. Lancet Oncology. 2020), 2) a retrospective study of postmenopausal patients with HR+/HER2-/Luminal B advanced BC treated with CDK4/6i plus ET in the first line setting at Hospital Clinic Barcelona (hereafter CDK cohort). PAM50 risk of relapse (ROR) and Ki67 levels were considered as outcome for the CORALLEEN patients. Progression free survival (PFS) was available in the CDK cohort. Area under the ROC Curve (AUC) was used to estimate the discrimination performance of the model. Differences were tested for statistical significance using Wilcoxon rank-sum test. Hazard ratios were estimated using Cox regression to investigate the association with PFS. Results: The computational model used here describes the dynamics of relevant protein-protein and drug-protein interactions to the treatment of CDK4/6i plus ET. The model showed high agreement with the training data obtained from cell lines (Pearson correlation of 0.88 and 0.95). The ability of the trained model to predict treatment outcome in patients was validated in baseline samples of the CDK4/6i arm (n=51) and the chemotherapy arm (n=52) of the CORALLEEN trial, and baseline Luminal B primary tumors of the CDK cohort (n=19). For each patient, a response score was calculated by the model using the expression of 6 genes at baseline as input. This response score was significantly associated with patient response in both cohorts. The model identified patients with high Ki67 (AUC of 0.80 (95% CI 0.64 - 0.92)) and high ROR (AUC of 0.78 (95% CI 0.64 - 0.89)) after treatment in the CDK4/6i arm of the CORALLEEN cohort and was used to stratify patients into different response groups. The AUC in the chemotherapy arm of CORALLEEN for identifying high Ki67 was 0.44 (95% CI 0.29 - 0.58), indicating that the predictions are specific to CDK4/6i plus ET treatment. Additionally, stratification of patients in the CDK cohort into either two or three groups based on the response score was linked to PFS (HR=3.71 (95% CI 0.97 - 14.16), p=0.055 and HR=2.92 (95% CI 1.08 - 7.86), p=0.034, respectively). Conclusion: A mechanistic model was developed, trained on cell line data, and then used to predict treatment outcome of patients with HR+/HER2-/PAM50 Luminal B BC treated with CDK4/6i plus ET. This approach showed significant association with observed outcome and could be used to assign patients to different response groups, indicating the usefulness of the model as a potential marker for response. Citation Format: Leonard Schmiester, Fara Brasó-Maristany, Vessela Kristensen, Arnoldo Frigessi, Aleix Prat, Alvaro Köhn-Luque. A computational model of the mechanisms of action of combined endocrine therapy and CDK4/6 inhibition predicts outcome in patients with Luminal B breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-14-09.

Abstract PO2-01-13: Clinico-Pathological and Molecular Characterization of Early Hormone Receptor-Positive Breast Cancer in Young Women

Abstract Introduction Premenopausal women diagnosed with hormone receptor-positive (HR+)/HER2-negative (HER2-) early breast cancer (EBC) face a significantly higher risk of cancer recurrence and mortality compared to older women, particularly those diagnosed under the age of 40. The underlying causes behind this disparity remain largely unknown. Material and methods We retrospectively select tumour samples from patients (pts) diagnosed with HR+/HER2- EBC at Hospital Clinic (Barcelona, Spain) from May 2014 to March 2020 who had a PAM50/Prosigna assay (Veracyte) previously performed. This assay examines the expression of 50 genes involved in important breast cancer signaling pathways, as well as the intrinsic subtypes (IS) and the Risk of Recurrence (ROR) score. Our primary objective was to compare the distinct clinicopathological and molecular characteristics of HR+/HER2- EBC between two age groups: patients under 40 years old (Young EBC or YEBC) and those 40 years old and above (Older EBC or OEBC). Disease-free survival (DFS) was defined as the time between diagnosis and the first recurrence. Comparisons between groups were carried out using chi-square tests (categorical variables). Additionally, we performed a two-class unpaired Significance Analysis of Microarrays (SAM) with a false discovery rate (FDR) less than 5% to identify genes with significantly different expression between YEBC and OEBC. The statistical significance level was set at less than 0.05. Results A total of 441 tumor samples from 420 patients were included in the analysis, with 5% (22/441) corresponding to YEBC. With a median follow-up of 64.5 months, there were 20 breast cancer (BC) recurrences (4.8%), 12 second cancers (2.9%) and 5 BC-related deaths (1.2%), all occurring in the OEBC group. Table 1 provides an overview of the main clinico-pathological and molecular characteristics. YEBC tended to have larger tumors, with 45.5% (10/22) measuring over 2 cm compared to 36.1% (151/419) in OEBC (p=0.376). YEBC also had a higher proportion of grade 3 tumors (18.18% versus 3.1% in OEBC, p=0.418) and lower expression of estrogen receptor (ER) as determined by immunohistochemistry (mean of 72.28% vs 88.36%, p=0.004). Regarding the PAM50 IS, there was a difference observed between YEBC and OEBC (p < 0.001). Specifically, YEBC patients exhibited a tendency towards a higher proportion of Luminal B tumors (54.6% versus 38.9% in OEBC, p=0.144), as well as non-Luminal subtypes such as Basal-like (18.2% versus 0.95% in OEBC, p< 0.001) and HER2E (4.6% versus 0.7% in OEBC, p=0.186). YEBC tended to have higher ROR (p=0.167), and to receive chemotherapy in a higher proportion, especially in the intermediate-risk group (p=0.004). In YEBC tumours, SAM analysis (p < 0.05) showed an overexpression of genes mainly related with proliferation (i.e., RRM2, MELK, MIK67), cell cycle progression (i.e., KNTC2, CDC20, MYBL2) and apoptosis inhibition (i.e., BIRC5). In OEBC there were an overexpression of genes related with the oestrogen receptor-signalling pathway (i.e., ESR1, NAT1, FOXA1, PGR). Luminal B tumours in YEBC showed an upregulation of genes related to proliferation, migration, and poor prognosis (i.e., KRT17, KRT5) compared to OEBC. However, since there were no recurrences in the YEBC group, differences in terms of DFS between the groups could not be calculated. Principio del formulario Final del formulario Conclusions YEBC exhibited a more advanced stage and a more aggressive intrinsic phenotype compared to OEBC. Additionally, these tumors showed a tendency to upregulate genes involved in proliferation, cell cycle progression, and survival, while downregulating genes related to hormone signaling pathways. These molecular characteristics may help explain the worse prognosis of YEBC compared to OEBC. However, further research is necessary to delve into the differential genomic characteristics that contribute to the unfavorable prognosis observed in patients diagnosed with HR+ EBC before the age of 40. Key clinical and molecular features in 441 biopsies Citation Format: Francisco Javier Muñoz-Carrillo, José Antonio Sola, Carme Crous, Esther Sanfeliu, Isabel Garcia-Fructuoso, Elia Seguí, Teresa Gorría, Raquel Gómez-Bravo, Barbara Adamo, Tomás Pascual, Olga Martínez-Sáez, Francesco Schettini, Pablo Rivera, Rosalía Cayuela, Montserrat Muñoz, Núria Chic, Maria Vidal. Clinico-Pathological and Molecular Characterization of Early Hormone Receptor-Positive Breast Cancer in Young Women [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-01-13.

Multicentre randomised trial of screening with sFlt1/PlGF and planned delivery to prevent pre-eclampsia at term: protocol of the PE37 study

IntroductionPre-eclampsia affects ~5%–7% of pregnancies. Although improved obstetric care has significantly diminished its associated maternal mortality, it remains a leading cause of maternal morbidity and mortality in the world. Term...

Rapid diagnostic tests for dengue would reduce hospitalizations, healthcare costs and antibiotic prescriptions in Spain: A cost-effectiveness analysis

BackgroundCurrent gold standard diagnostic techniques for dengue are expensive and time-consuming. Rapid diagnostic tests (RDTs) have been proposed as alternatives, although data about their potential impact in non-endemic areas is scarce. MethodsWe performed a cost-effectiveness analysis comparing the costs of dengue RDTs to the current standard of care for the management of febrile returning travelers in Spain. Effectiveness was measured in terms of potential averted hospital admissions and reduction of empirical antibiotics, based on 2015–2020 dengue admissions at Hospital Clinic Barcelona (Spain). ResultsDengue RDTs were associated with 53.6% (95% CI: 33.9–72.5) reduction of hospital admissions and were estimated to save 289.08–389.31€ per traveler tested. Moreover, RDTs would have avoided the use of antibiotics in 46.4% (95% CI: 27.5–66.1) of dengue patients. DiscussionImplementation of dengue RDTs for the management of febrile travelers is a cost-saving strategy that would lead to a reduction of half of dengue admissions and a reduction of inappropriate antibiotics in Spain.

Abstract P2-11-12: Pattern of distant relapse according to intrinsic molecular subtype in patients with HER2-positive breast cancer: a combined analysis of ShortHER, CherLOB, and two institutional cohorts

Abstract Background: All intrinsic molecular subtypes are represented among HER2-positive breast cancer, with implications on clinical outcome and treatment sensitivity. The impact of molecular subtypes on the pattern and site of relapse is largely unexplored. Methods: 677 patients with HER2-positive early breast cancer from the Shorther trial (n=437), the CherLOB trial (n=84) and two Institutional cohorts (Istituto Oncologico Veneto IRCCS Padova n=39 and Hospital Clinic Barcelona n=117) were included. Only patients with available PAM50 intrinsic molecular subtyping were considered. We analyzed the incidence of distant relapse (at any site and at specific sites) as the first event. Cumulative incidence was estimated according to competing risk analysis (Fine and Gray’s method). Competing risk regression was used to calculate the subdistribution Hazard Ratios (subHR) and their 95% Confidence Interval (CI). Results: The distribution of molecular subtypes was: 130 LumA (19%), 75 LumB (11%), 347 HER2-e (51%), 46 Basal (7%), 79 Normal (12%). Median follow up was 8.4 years (95%CI 8.2-8.6). The 10-yr cumulative incidence rates of distant relapse as first event were: LumA 7.9%, LumB 14.8%, HER2-e 14.7%, Basal 15.5%, Normal 10.4% (HER2-e vs LumA: SubHR 2.21, 95%CI 1.05-4.64, p=0.037). Table 1 shows the 5-yr and 10-yr cumulative incidence rates of distant metastases at specific sites (as first event) according to intrinsic subtype. HER2-e enriched and Basal tumors were more prone as compared to other subtypes to develop brain and lung metastasis as first event, respectively. Isolated brain metastases without extracranial disease occurred only in patients with HER2-e tumors. All brain metastases as first event occurred within 5 years from diagnosis. Bone-only disease as first event was less frequent in HER2-e and Basal subtype (subHR HER2-e vs LumA: 0.32, 95%CI 0.10-10.4. p=0.058). Next, we analyzed the frequency of site-specific first metastasis among patients who experienced a distant metastasis as first event (n=77). Lung metastases were more frequent in Basal tumors (LumA 25.0%, LumB 20.0%, HER2-e 24.4%, Basal 71.4%, Normal 0.0%, p=0.037) and bone metastases were more frequent in Luminal tumors (LumA 100.0%, LumB 60.0%, HER2-e 31.1%, Basal 42.9%, Normal 57.1%, p=0.006). Among 45 HER2-e patients with a first distant relapse, 25.6% were diagnosed with a brain metastasis and 15.6% had brain-only disease. Conclusions: Molecular subtypes influence the metastatic behaviour of clinically HER2-positive breast cancer. These results, if further validated, may have implication in planning personalized monitoring strategies. Table 1. 5-yr and 10-yr cumulative incidence rates of distant metastasis at specific sites (as first event) according to intrinsic subtype. Citation Format: Maria Vittoria Dieci, Giancarlo Bisagni, Stefania Bartolini, Antonio Frassoldati, Daniele Giulio Generali, Federico Piacentini, Gaia Griguolo, Enrico Tagliafico, Fara Brasó-Maristany, Nuria Chic, Francesca Porra, Roberto Vicini, Roberto D’Amico, Sara Balduzzi, Aleix Prat, PierFranco Conte, Valentina Guarneri. Pattern of distant relapse according to intrinsic molecular subtype in patients with HER2-positive breast cancer: a combined analysis of ShortHER, CherLOB, and two institutional cohorts. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-12.

Abstract P2-23-16: Clinico-Pathological and Molecular Characterization of HER2-Enriched Breast Tumors Independently of HER2 Status

Abstract INTRODUCTION: Breast cancer (BC) is a highly prevalent and heterogeneous disease, entailing different so-called intrinsic subtypes (IS) according to gene expression, namely Luminal A, Luminal B, HER2-Enriched (HER2E) and Basal-like, as well as a normal breast-like group. The HER2E is still a poorly understood entity, which needs further biologic characterization to improve therapeutic management. MATERIAL AND METHODS: Patients (pts) treated at Hospital Clinic (Barcelona, Spain) over 18 years with a diagnosis of metastatic BC, with available matched primary and metastatic tumor samples for gene expression analyses were retrospectively recruited. Using the nCounter® Breast Cancer 360 panel, we studied the expression of 776 genes pertaining to different tumor and immune pathway-related signatures, with a focus on HER2E vs. non-HER2E tumors. Significant changes were considered at a false discovery rate (FDR) < 5%. Main clinicopathological features were also compared. IS changes from primary to metastatic disease were assessed. RESULTS: Ninety-one pts with paired tumor samples were included. Briefly, primary tumors were 67.0% hormone receptor-positive (HR+)/HER2-negative (HER2-), 14.8% were HER2-positive (HER2+) and 18.2% were triple-negative (TNBC). IS distribution in primary tumors was the following: 25 Luminal A (28%), 22 Luminal B (24%), 24 HER2E (26%), 12 Basal-like (13%), and 8 Normal-like (9%). In contrast, IS distribution in metastatic tumors was the following: 13 Luminal A (14%), 22 Luminal B (24%), 34 HER2-E (37%), 16 Basal-like (18%), and 6 Normal-like (7%). The HER2E disease proved to be a relatively stable subtype, with 16 (66.7%) tumors not changing IS in the transition to metastatic disease (p=0.078). Particularly, within HR+/HER2-, HER2+ and TNBC, 8/12 (66.7%), 8/10 (80.0%) and 1/2 (50.0%) tumors remained HER2E. Conversely, an overall significant switch from Luminal to non-Luminal tumors at the metastatic progression was observed (p=0.031), with 14/19 (73.7%) new non-Luminal BC being HER2E. When considering all primary and metastatic tumors, HER2E were observed to be less frequently estrogen receptor (ER) positive than non-HER2E tumors (55.8% vs. 78.7%; p=0.002), with lower mean progesterone receptor (PR) levels (15.3% vs. 25.8%; p=0.027). Compared to the other subtypes (as a group), the PAM50 risk of recurrence score (ROR-P) was higher for HER2E tumors (59.1 vs. 41.7; p < 0.001), which were also more frequently HER2+ (36.5% vs. 5.8%) and less likely HR+/HER2- (50.0% vs. 73.6%) and TNBC (13.5% vs. 20.7%), compared to non-HER2E (p < 0.001). No significant differences in grade, TILs, Ki67 and histotype were observed. Overall, 140/776 genes were significantly downregulated in HER2E vs. non-HER2E tumors, including genes related to cell adhesion, migration, DNA damage repair, apoptosis, estrogen signalling pathway, senescence. Conversely, 178/776 genes were significantly upregulated, including the tyrosine-kinase receptor FGFR4, genes involved in nuclear activity, DNA transcription regulation, MAP-kinase signaling pathways, proliferation, cytokine response, epithelial-to-mesenchymal transition (EMT), cell cycle progression, and immune-related genes such as CD274 (PD-L1 gene). DISCUSSION: A switch towards more aggressive IS from primary to advanced disease was observed, with an increase in HER2E prevalence. HER2E tumors, which tend to maintain their IS at the metastatic disease, showed upregulation of genes related to proliferation, survival and EMT, coherently with their well-known worse prognosis. FGFR4 and CD274 upregulation, along with downregulation of genes involved in DNA damage repair suggest these tumors might benefit from targeted therapeutic approaches. Genomic higher risk was not convoyed by consistent clinicopathological features, except for lower PR levels and HER2 overexpression at IHC. Further characterization according to primary/metastatic and HR status is ongoing. Intrinsic subtype distribution across primary and metastatic breast tumors Citation Format: Francisco Javier Muñoz-Carrillo, Laia Paré, Benedetta Conte, Adela Rodríguez, Patricia Galván, Esther Sanfeliu, Blanca González-Farré, Claudette Falato, Isabel Garcia-Fructuoso, Barbara Adamo, Nuria Chic, Olga Martínez-Sáez, Tomás Pascual, Reinaldo Moreno, Montserrat Muñoz, Fara Brasó-Maristany, Aleix Prat, Francesco Schettini, Maria Vidal. Clinico-Pathological and Molecular Characterization of HER2-Enriched Breast Tumors Independently of HER2 Status [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-23-16.

Rapid diagnostic tests for dengue would reduce hospitalizations, healthcare costs and antibiotic prescriptions in Spain: A cost-effectiveness analysis

BackgroundCurrent gold standard diagnostic techniques for dengue are expensive and time-consuming. Rapid diagnostic tests (RDTs) have been proposed as alternatives, although data about their potential impact in non-endemic areas is scarce. MethodsWe performed a cost-effectiveness analysis comparing the costs of dengue RDTs to the current standard of care for the management of febrile returning travelers in Spain. Effectiveness was measured in terms of potential averted hospital admissions and reduction of empirical antibiotics, based on 2015–2020 dengue admissions at Hospital Clinic Barcelona (Spain). ResultsDengue RDTs were associated with 53.6% (95% CI: 33.9–72.5) reduction of hospital admissions and were estimated to save 289.08–389.31€ per traveler tested. Moreover, RDTs would have avoided the use of antibiotics in 46.4% (95% CI: 27.5–66.1) of dengue patients. DiscussionImplementation of dengue RDTs for the management of febrile travelers is a cost-saving strategy that would lead to a reduction of half of dengue admissions and a reduction of inappropriate antibiotics in Spain.

Morphological evaluation of melanocytic lesions with three-dimensional line-field confocal optical coherence tomography: correlation with histopathology and reflectance confocal microscopy. A pilot study.

Line-field confocal optical coherence tomography (LC-OCT) is a new invivo emerging technique that provides cellular resolution, allows deep imaging (400 μm) and produces real-time images in both the horizontal and vertical plane and in three dimensions. No previous description of different subtypes of melanocytic lesions and their correlation with histopathology and reflectance confocal microscopy has been reported. To describe the features of melanocytic lesions by LC-OCT and their correlation with histopathology and reflectance confocal microscopy (RCM) findings. Selected melanocytic benign lesions and melanomas were imaged invivo with RCM and LC-OCT at the Fundación Hospital Clinic (Barcelona, Spain). A minimum area of 4 × 4 mm (block image) at four depths (stratum granulosum, suprabasal, layer dermoepidermal junction and upper dermis) were acquired with RCM and a minimum of three cubes with LC-OCT. Horizontal, vertical sections and three-dimensional (3D) cubes of LC-OCT were matched with RCM (Vivablock two-dimensional composite mosaic) and histopathology, with ~5 μm lateral resolution accuracy (the same cell nuclei were measured in X, Y and Z) and evaluated by three observers experienced in using RCM and histopathology. In total, 12 melanocytic tumours (2 insitu melanomas, 2 invasive melanomas, 4 atypical naevi, 2 intradermal naevi, 1 compound naevus and 1 junctional naevus) were included. High correlation with 5 μm accuracy between RCM and LC-OCT was observed for each tumour. The 3D images of melanocytic lesions were obtained with cellular resolution and correlated with both RCM and histopathology, allowing an understanding of the architecture and precise correlation at the cellular level with RCM. Similarities between LC-OCT and RCM for the described diagnostic features and architecture (nests of melanocytic cells, ringed and meshwork pattern, and cellular details of tumour cells as dendritic and pagetoid cells) were confirmed. The main advantage of diagnosis by RCM fixed probe was the ability to produce larger scans of the lesion using mosaicing compared with an LC-OCT handheld probe. LC-OCT allows the architectural and cellular description of different types of melanocytic lesions. LC-OCT showed high correlation with histopathology (vertical sections) and RCM (horizontal sections) in melanocytic lesions. Diagnostic criteria for RCM were similar to those for LC-OCT.

Susac Syndrome: Description of a Single-Centre Case Series.

This study describes the clinical characteristics, diagnostic results, treatment regimens, and clinical course of a cohort of patients with Susac syndrome (SS). It is a retrospective observational study of all patients with the diagnosis of SS evaluated at the Hospital Clinic (Barcelona, Spain) between March 2006 and November 2020. Nine patients were diagnosed with SS. The median time from the onset of the symptoms to diagnosis was five months (IQR 9.0), and the median follow-up time was 44 months (IQR 63.5). There was no clear predominance of sex, and mean age of symptoms onset was 36 years (range 19-59). Six patients (67%) presented with incomplete classical clinical triad, but this eventually developed in six patients during the disease course. Encephalopathy, focal neurological signs, visual disturbances, and hearing loss were the most frequent manifestations. Brain magnetic resonance imaging showed callosal lesions in all patients. Most were in remission within two years. Only four patients met the proposed criteria for definite SS. When SS is suspected, a detailed diagnostic workup should be performed and repeated over time to identify the clinical manifestations that will lead to a definite diagnosis.

Perioperative Management for the First Uterine Transplant in Southern Europe: A Case Report

The aim of this study was to describe perioperative management concerning the living donor uterine transplantation program at the Hospital Clinic (Barcelona, Spain), in the first successful procedure in Southern Europe. Before the date of surgery, both the donor and the recipient are evaluated in the outpatient clinic to detect any possible comorbidities that might complicate or altogether disallow the procedure. In the donor, with a robotically performed surgery, complications regarding cerebral and upper airway edema, as well as reduced access to the patient once docking occurs, are of utmost importance. An aggressive antithrombotic regimen must be in place that includes heparin administered both to the donor and the recipient and aspirin to the recipient. Different strategies to reduce ischemia-reperfusion injury have been studied, with reduced ischemia times currently being the most effective. After surgery, both donor and recipient were taken to the intensive care unit overnight, transferred to the conventional ward the following day and discharged from the hospital within the week. The recipient had her first menstrual period 47 days after the surgery. The description of challenges regarding perioperative care of women who undergo uterine transplant programs and the rationale in anesthetic management may help other teams implant this program as a solution for a disease that profoundly impairs quality of life.

Somatostatin Therapy Improves Stellate Cell Activation and Early Fibrogenesis in a Preclinical Model of Extended Major Hepatectomy

Background: Liver resection is effective treatment for primary and secondary liver tumors, though clinical applicability is limited by remnant liver mass and quality. Aims: Perform major hepatic resections in pigs to define changes associated with sufficient and insufficient remnants and improve liver-specific outcomes through continuous somatostatin infusion. Methods: Three experimental groups were performed: 75% hepatectomy (75H), 90% hepatectomy (90H), and 90% hepatectomy with somatostatin (90H+SST). In each group, animals were followed for 24 hours (N=6) and 5 days (N=6). Results: After hepatectomy, portal venous pressure gradient was higher in 90H versus 75H and 90H+SST (8[3-13] mmHg vs. 4[2-6] mmHg and 4[2-6] mmHg, respectively, P <0.001). After 24 hours, changes were observed in 90H associated with stellate cell activation and collapse of sinusoidal lumen (area 23.5±3.6% 90H vs. 31.1±3.5% 75H, P <0.001, and 30.9±4.3% 90H+SST, P=0.008). Collagen chain type 1 alpha 1 mRNA expression was higher, extracellular matrix width less, and percentage of collagen-staining areas greater at 24 hours in 90H versus 75H and 90H+SST.After 5 days, remnant liver mass was higher in 75H and 90H+SST versus 90H (469±33 g and 463±79 g vs. 313±107, respectively, P=0.003), and Ki-67 immunostaining was higher in 90H+SST versus 75H and 90H (10±7 high-power field-1 vs. 2±2 high-power field-1 and 5±6 high-power field-1, respectively, P<0.001). More TUNEL-staining cells were observed in 90H versus 75H and 90H+SST at 5 days. Conclusions: Perioperative somatostatin modified portal pressure, injury, apoptosis, and hepatic stellate cell activation, stemming early changes related to hepatic fibrogenesis seen in liver remnants not receiving treatment. Funding: Research was supported by FIS Grant 15/01092 from the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovacion, Spain. Amelia J. Hessheimer was supported by the “Ajut Josep Font” from the Hospital Clinic Barcelona. Lilia Martinez de la Maza was supported by the Fundacio Catalana de Trasplantament. Declaration of Interest: Amelia J. Hessheimer and Constantino Fondevila have received research funding and consultancy fees from Guanguong Shunde Innovative Design Institute, Guangdong, China. The remainder of the authors have nothing to declare. Ethical Approval: The University of Barcelona Animal Experimentation Unit is authorized by the Catalan Department of Agriculture, Husbandry, and Fisheries (authorization number B9900020), registered in the General Registry of Livestock Facilities (ES080190036536), and accredited by the International Standards Organization (ISO 9001:2015). Animals were cared for according to the guidelines of the Catalan Department of the Environment Commission on Animal Experimentation and University of Barcelona Committee on Ethics in Animal Experimentation, which approved the study protocol.

COVID-19 in Liver Transplant Candidates: Pre- and Post-Transplant Outcome

Background: The impact of COVID-19 on patients on the waiting list for liver transplantation (LT) and on their post-LT course is presently unknown. Methods: Data from consecutive adult LT candidates with COVID-19 were collected across Europe in a dedicated registry and analyzed.Findings: From February 21st to November 20th, 2020, 136 adult cases with laboratory confirmed SARS-CoV-2 infection from 33 centers in 11 European countries were collected, with 113 having COVID-19. Thirty-seven (37/113, 32·7%) patients died after a median of 18 (10-30) days, respiratory failure being the major cause (33/37, 89·2%). The 60-day mortality risk did not significantly change between first (35·3%, 95% CI 23·9-50·0) and second wave (26·0%, 95% CI 16·2-40·2). Multivariable Cox regression analysis showed lab-MELD score ≥15 (MELD 15-19 HR 6·09, 95% CI 2·01-18·45; MELD ≥20 HR 5·21, 95% CI 1·76-15·45) and dyspnea on presentation (HR 4·10, 95% CI 2·09-8·06) being the two negative independent factors for mortality. The mortality risk reached 49·2% (31/63) in patients with decompensated cirrhosis and lab-MELD score ≥15. Twenty-six patient received a LT after a median time of 78.5 (IQR 44-102) days and 25 (96%) are alive after median follow-up of 118 days (IQR 31-170).Interpretation: Increased mortality in LT candidates with COVID-19 (32·7%), reaching 49·2% in those with decompensated cirrhosis and lab-MELD score ≥15, with no significant difference between first and second wave of the pandemic. Respiratory failure was the major cause of death. The dismal prognosis of patients with decompensated cirrhosis supports the adoption of strict preventative measures and the urgent testing of vaccination efficacy in this population. Prior SARS-CoV-2 symptomatic infection did not affect early post-transplant survival (96%).Funding: No funding source.Declaration of Interests: None to declare. Ethics Approval Statement: Data was collected in accordance with General Data Protection Regulation (GDPR), the European Union legislation and the ELTR privacy policy. Reg. HCB/2020/0479 released by CLINICAL RESEARCH ETHICS COMMITTEE from Hospital Clinic Barcelona

Medicalised Hotel as an Alternative to Hospital Care for Management of Non-Critical COVID-19: A Prospective Cohort Study

Background: COVID-19 entails large overloads of hospitals’ capacity. Alternatives to conventional hospitalization are key to optimize health systems resilience during outbreaks of the pandemic.Methods: From March 25th to May 25th 2020 the Hospital at Home Unit (HaH) of Hospital Clinic Barcelona adapted a 500-bed hotel for treating patients with non-critical COVID-19.Findings: 516 patients were admitted to the hotel during the study period. Median age was 57 . 5 years (IQR 45-70), 304 (59%) were referred from hospital wards and 196 (38%) from the emergency room. Median length of stay was 9 days in the hotel (IQR 6-13). Bilateral infiltrates were present in the chest x-ray of 348 (68%) patients. Treatment for COVID-19 was administered to 494 (96%) patients, 137 (27%) of whom had it interrupted due to adverse events. Complications after 14 days from symptoms onset were detected in 85 (16 . 5%) patients: 24 (5%) pulmonary embolism, 23 (4 . 5%) pulmonary fibrosis, 50 (9.7%) organising pneumonia, 133 (26%) neutropoenia. History of smoking, oxygen requirement, bacterial infection and prior ICU admission were predictors of subacture complications. Twenty-eight (5 . 5%) patients required transfer back to hospital. Chronic kidney disease, oxygen requirement and previous shock were predictors of readmission. Two patients (0 . 4%) died after hospital readmission.Interpretation: The adaptation of hotels for the management of COVID-19 patients seems to be safe and efficacious, therefore providing a suitable alternative to alleviate hospital overload during the pandemic. Accurate selection of patients for transfer based on the clinic and potential severity is key.Funding: None.Declaration of Interests: None of the authors declare competing interests with regards to the current work or at all.Ethics Approval Statement: The Ethical Board of the Hospital Clínic evaluated and approved the study protocol (HCB.2020.0443). A waiver for informed consent was granted due to the state of infectious disease emergency

Sars-Cov-2 Infection and Systemic Light Chain Amyloidosis: The International Society of Amyloidosis' Survey

Introduction: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has become a global health crisis since it was first reported in December 2019. In a subset of infected subjects, pneumonia, multi-organ failure, and eventually death can occur. Frail patients and those with comorbidities are believed to be at increased risk of severe manifestations of SARS-CoV-2 infection. Patients with light chain (AL) amyloidosis have a hematologic malignancy that causes multi-organ dysfunction and can be at higher risk of complications and death. The International Society of Amyloidosis (ISA) has issued a guidance (Kastritis et al. BJH 2020, https://cms.cws.net/content/isaamyloidosis.org/files/ISA%20recommendations%20Covid-19%20v_%203_3.pdf) for patients with amyloidosis during the pandemic and called for an international data collection in April 2020. Aim of this study is to report the preliminary data of the ongoing international survey regarding systemic AL amyloidosis and COVID-19.Methods: The survey was proposed by the ISA Board and approved by the coordinating institution's Ethics Committee. All members of the ISA were invited to participate by email and a link for participation is online on ISA website. RedCap software was used for the data collection.Results: Twelve Institutions requested the access to the data collection system from 7 countries. At the data lock of July 26, 2020, 29 patients with systemic amyloidoses were collected from 7 different Institutions. Systemic AL amyloidosis patients reported so far were 19: 12 from the Pavia Amyloidosis Research and Treatment Center (Italy), 3 from the Boston Medical Center (USA), and 1 patient each from the Columbia University Hospital (New York, USA), Hospital Clinic (Barcelona, Spain), Clinica Universitaria de Navarra (Navarra, Spain) and Amyloidosis Centrum (Heidelberg, Germany). Eleven (58%) had heart involvement, 8 (42%) had kidney and two or more organs were involved in 9 patients (47%). The most frequent comorbidities reported were history of hypertension in 7 (37%) and cardiovascular diseases in 3 (16%). Four (21%) patients were newly diagnosed and treatment-naïve at the time SARS-CoV-2 infection was documented. The remaining 15 patients had received a median number of 2 previous lines of therapy (range 1-3). Nine (47%) patients were on active chemotherapy at the time of COVID-19 infection. Five were receiving daratumumab combinations, and the 4 remaining patients were on cyclophosphamide, bortezomib and dexamethasone, oral melphalan and dexamethasone, lenalidomide and ixazomib. Relevant concomitant medications were anti-hypertensive drugs in 26% of cases and diuretics in 21%. One patient was on dialysis. COVID-19-related symptoms were fever 11 (58%), cough 8 (42%), anosmia and ageusia. Pneumonia was documented in 10 (53%) patients, 5 of whom had acute respiratory distress syndrome (ARDS) (26%). Four of them were treated with non-mechanical ventilation and one accessed intensive care support. Three of the 5 patients with severe COVID-19 had heart involvement, 2/5 had concomitant heart and kidney involved and 3 was infected while on active chemotherapy. Azytromicin was used in 6 (26%) cases, which was in combination with hydroxycloroquine in 4 of them. Three patients received steroids as treatment for SARS-CoV-2 infection, while anticoagulant therapy was used only in two cases. Lopinavir, tocilizumab and sarilumab were used in one patient each. Four patients (21%) died in the whole cohort. Three had ARDS and one patient died few weeks after the recovery of COVID-19 infection. All deceased patients had heart involvement, 2 were on active therapy (daratumumab plus bortezomib and ixazomib plus dexamethasone). Two patients with kidney involvement at diagnosis, one with ARDS and one with a radiological documented pneumonia treated with non-mechanical ventilation recovered from COVID-19 but developed subsequent worsening of renal function, requiring dialysis in one case.Conclusions: The fatality rate and the proportion of patients with severe COVID-19 in this series is in the higher range of reports from the general population. Severe SARS-CoV-2 infection can result in renal failure in patients with renal AL amyloidosis.DisclosuresMilani:Janssen: Other: Speaker honoraria; Pfizer: Other: Speaker honoraria; Celgene: Other: Travel support. Sanchorawala:Oncopeptide: Research Funding; Abbvie: Other: advisory board; Proclara: Other: advisory board; Caleum: Other: advisory board; Regeneron: Other: advisory board; Prothena: Research Funding; Takeda: Research Funding; Janssen: Research Funding; UpToDate: Patents & Royalties; Caelum: Research Funding; Celgene: Research Funding. Cibeira:Janssen: Honoraria, Membership on an entity’s Board of Directors or advisory committees, Other: Educational lectures; Akcea Therapeutics: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Celgene: Honoraria, Other: Educational lectures; Amgen: Honoraria, Other: Educational lectures. Schönland:Janssen, Prothena, Takeda: Honoraria, Other: travel support to meetings, Research Funding. Palladini:Celgene: Other: Travel support; Jannsen Cilag: Honoraria, Other.

Care of older people with Cognitive Impairment or Dementia Hospitalized in Traumatology Units (CARExDEM): a quasi-experiment

BackgroundIn our context, as in other European countries, care of patients with cognitive disorders or dementia still represents a major challenge in hospital settings. Thus, there is a need to ensure quality and continuity of care, avoiding preventable readmissions, which involve an increase in public expenses. Healthcare professionals need to acquire the necessary knowledge and skills to care for hospitalized patients with cognitive disorders and dementia.MethodsA quasi-experimental design with repeated observations, taken at baseline, post-intervention, and at one and three months post-intervention, in people hospitalized with cognitive disorders or dementia. The study will be carried out in four general hospitals in Spain and will include 430 PwD and their caregivers. The intervention was previously developed using the Balance of Care methodology where nurses, physicians, social workers and informal caregivers identified the best practices for this specific care situation. We aim to personalize the intervention, as recommended in the literature. The study has an innovative approach that includes new technologies and previous scientific evidence. Valid, reliable instruments will be used to measure the intervention outcomes. Quality of care and comorbidity will be analyzed based on the use of restraints and psychotropic medication, pain control, falls, functional capacity and days of hospitalization. Continuity of care will be measured based on post-discharge emergency hospital visits, visits to specialists, cost, and inter-sectorial communication among healthcare professionals and informal caregivers. Statistical analysis will be performed to analyze the effect of the intervention on quality of care, comorbidity and continuity of care for patients with dementia.DiscussionOur aim is to helping healthcare professionals to improve the management of cognitive disorders or dementia care during hospitalization and the quality of care, comorbidity and continuity of care in patients with dementia and their informal caregivers. Moving towards dementia-friendly environments is vital to achieving the optimum care outcomes.Trial registrationRegistered in Clinical Trials. ClinicalTrials.gov Identifier: NCT04048980 retrospectively registered on the 6th August 2019. https://clinicaltrials.gov/Protocol Record HCB/2017/0499.Sponsor: Hospital Clinic Barcelona.

MP52-03 THE EUROPEAN EXPERIENCE IN ROBOT-ASSISTED KIDNEY TRANSPLANTATION: LEARNING CURVE

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation & Vascular Surgery II (MP52)1 Apr 2020MP52-03 THE EUROPEAN EXPERIENCE IN ROBOT-ASSISTED KIDNEY TRANSPLANTATION: LEARNING CURVE Andrea Gallioli*, Angelo Territo, Romain Boissier, Riccardo Campi, Graziano Vignolini, Mireia Musquera, Antonio Alcaraz, Karel Decaestecker, Volkan Tugcu, Davide Vanacore, Sergio Serni, and Alberto Breda Andrea Gallioli*Andrea Gallioli* More articles by this author , Angelo TerritoAngelo Territo More articles by this author , Romain BoissierRomain Boissier More articles by this author , Riccardo CampiRiccardo Campi More articles by this author , Graziano VignoliniGraziano Vignolini More articles by this author , Mireia MusqueraMireia Musquera More articles by this author , Antonio AlcarazAntonio Alcaraz More articles by this author , Karel DecaesteckerKarel Decaestecker More articles by this author , Volkan TugcuVolkan Tugcu More articles by this author , Davide VanacoreDavide Vanacore More articles by this author , Sergio SerniSergio Serni More articles by this author , and Alberto BredaAlberto Breda More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000914.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Robot-assisted kidney transplantation (RAKT) was recently introduced and an ERUS group constituted to draw together early European experiences at the highest volume centers using this minimally invasive technique. Therefore, the aim of the study is to report the learning curve in RAKT, evaluating surgical and functional results in the five highest volume centers of the ERUS group. The second objective of the study is to evaluate the reproducibility of the learning curve. METHODS: All consecutive RAKTs performed in the five highest volume centers of the ERUS RAKT group, i.e. Fundaciò Puigvert and Hospital Clinic (Barcelona), Careggi Hospital (Florence), Ghent University Hospital (Ghent), and Bakirkoy Research Hospital (Istanbul), were reviewed. Shewhart control charts and cumulative summation (CUSUM) graphs were generated to assess the learning curve according to surgical timings and renal graft function (glomerular filtration rate) at days 7, 30 and at 1 year. Linear regressions were performed to compare the learning curves of each surgeon. P values <0.05 were considered statistically significant. The statistical package SPSS V 25 and GraphPad Prism were used. RESULTS: Arterial anastomosis time was below the alarm/alert line in 93.3%/88.9% of RAKTs, while venous anastomosis time was below the alarm/alert line in 88.9%/73.9%. The non-anastomotic rewarming time (RWT) exceeded +3SD in 24.7% of procedures and +2SD in 37.1%. In only 46% cases was the RWT below the alert line. The ureterocystoneostomy time was below +2 and +3SD in 87.9% and 90.2% of cases, respectively. CUSUM showed that the learning curve for arterial anastomosis required up to 35 (mean=16) cases. Complications and delayed graft function rates decreased significantly and reached a plateau after the first 20 cases. A similar conclusion was reached for venous anastomosis, which may need more than 40 procedures (mean=24). The plateau in the ureterocystoneostomy curve was reached within 30 RAKTs in 4/5 centers (mean=17). The plateau for RWT was reached within 23 procedures at center 1, 44 at center 2, and 38 at center 3 (mean 35 cases); centers 4 and 5 did not reach the plateau. Interestingly, the curves for non-anastomotic time during RWT resemble those for RWT. On the linear regression model, all the anastomotic times were comparable. The slopes in respect of non-anastomotic time during RWT were slightly different (p=0.0006), as was also true for RWT itself (p=0.007). CONCLUSIONS: A minimum of 35 cases is necessary to reach reproducibility in terms of anastomosis time, rewarming time and functional results. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e772-e773 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Andrea Gallioli* More articles by this author Angelo Territo More articles by this author Romain Boissier More articles by this author Riccardo Campi More articles by this author Graziano Vignolini More articles by this author Mireia Musquera More articles by this author Antonio Alcaraz More articles by this author Karel Decaestecker More articles by this author Volkan Tugcu More articles by this author Davide Vanacore More articles by this author Sergio Serni More articles by this author Alberto Breda More articles by this author Expand All Advertisement PDF downloadLoading ...

Phase Ib Study of the Anti-TIM-3 Antibody MBG453 in Combination with Decitabine in Patients with High-Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)

Phase Ib Study of the Anti-TIM-3 Antibody MBG453 in Combination with Decitabine in Patients with High-Risk Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML)

CN89 - CART-19: A comparative between literature versus experience

BackgroundCART-19 therapy is an immunotherapy treatment based in extracorporeal and synthetic modification of T-lymphocytes from the patient that goes through the therapy. This therapy is used in treatment of haematological cancers like chronic lymphocytic leukaemia (CLL) and acute lymphoblastic leukaemia (ALL) and it can be administered through one aliquot or three aliquots. It is a new therapy recently introduced in cancer treatment which introduces multiple challenges like side effects management. Its main side effect is cytokine release syndrome (CRS). The aim of this study is to compare the side effects observed in patients treated with CART-19 therapy versus side effects described in the literature. MethodsThis is an observational, transversal and retrospective study based in medical records review. The patients included in this study are adults treated with CART-19 therapy in Hospital Clinic Barcelona between January 2017 and April 2019. Data analysis has been done through Excel programme and taking into account clinical variables like: age, diagnosis, arterial pressure, heart rate, number of aliquots and Intensive Care Unit (UCI) requirement. ResultsA total of 27 CART-19 therapies have been administered. 70,4% from infusions have been done in patients with a diagnosis from ALL. The main side effects that have been observed are hypotension in a 29,6%, tachycardia in 22,2% and headache in 11,1%. Fever has been observed in a 85,2% of the infusions and it has appeared in the first 24hours post-infusion in a 63% of the cases. A high percentage of the infusions have been administered in one aliquot (70,4%). Only in an 29,8% of the cases the patient needed a transfer to an UCI and a 22,2% needed Tocilizumab administration for CRS decrease. ConclusionsThe main conclusion obtained is that observed side effects in patients that have received CART-19 therapy coincide with the ones described in literature, without any new appearance. It is important to emphasise that fever has appeared in patients independent of the number of aliquots received and clinical variables affected. On the other hand, low incidence of neurological and gastrointestinal affections has been observed. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

322P - A retrospective gene expression analysis of surgically-removed breast cancer brain metastasis (BCBM)

BackgroundThe incidence of BCBM is increasing as a result of both improved diagnostic techniques and longer survival due to better treatment approaches. However, it is still a challenging situation occasioned by the poor responses to different standard therapies, representing an unmet medical need. Determining the molecular profile may be clinically relevant in order to improve the outcome of our patients (pts). MethodsThis is an observational retrospective study including BC-pts who had undergone surgery of BCBM in Hospital Clinic (Barcelona, Spain) between January 2000 and December 2017. RNA was isolated from FFPE tumor tissue and the expression of 55 BC-related genes was assessed on the nCounter. Median progression free survival (mPFS) and overall survival (mOS) were calculated using the Kaplan-Meier method. The association of the expression of each gene with mPFS was evaluated using univariate Cox-models. The same gene expression assay was tested BCBM-paired primary tumor samples. Results20 pts with resected BMBC were included. Median age at diagnosis of BCBM was 57.8years (y). mOS from diagnosis of BCBM was 20.22 months (range, 0.67-64.50months). The intrinsic subtype distribution was 45% Basal-like, 20% HER2-enriched (HER2-E), 10% Luminal A, 20% Luminal B and 5% Normal-like. High expression of ESR1and PGR (determined as above the median) and low expression of MKI67were related with better mOS (p=0.008, p=0.038 and p=0.0165). 9 matched-paired samples of primary BC and BCBM were analyzed and 4 (44.4%) PAM50 discordances (2 Luminal B shifted to Luminal A, 1 Normal-like to Basal-like and 1 HER2-E to Luminal B) were observed. Finally, down-regulation of CD8Aand PDL1expression between primary and BCBM (p=0.0234 and p=0.0367, respectively) was observed. ConclusionsNon-luminal intrinsic subtypes are more prevalent in resected BCBM, and gene expression might predict OS. Our data suggest that BCBM can elude the immune surveillance through downregulation of immune genes leading to an immunosuppressed environment. Our analysis shows the value of analyzing gene expression both by cancer subtype and metastatic origin, but further characterization is needed. Legal entity responsible for the studyTranslational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute, Barcelona, Spain. FundingFundación Científica Asociación Española Contra el Cáncer (PRÁCTICAS AECC CURSO ACADÉMICO 2018 to M.M-L). DisclosureM. Vidal: Speaker Bureau / Expert testimony: Roche; Speaker Bureau / Expert testimony: Daiichi Sankyo; Speaker Bureau / Expert testimony: Novartis. M. Muñoz: Travel / Accommodation / Expenses: Roche. A. Prat: Advisory / Consultancy: Nanostring Tech. All other authors have declared no conflicts of interest.

CN90 - Unplanned emergency department use by people receiving ambulatory anti-cancer agents with potential febrile neutropenia

BackgroundRecent advances in cancer therapies have resulted in a greater number of people receiving chemotherapy in ambulatory care settings worldwide. In Spain emergency departments, is the single point of entry to acute inpatient services, and therefore play a pivotal role in the immediate management of chemotherapy complications. This study set out to explore ED use by ambulatory patients receiving anti-cancer agents in febrile neutropenia episodes. Data will contribute to service innovation for optimal patient care and health service efficiency. MethodsA 12 month retrospective observational study of unplanned ED presentation by patients within 30 days of receiving anti-cancer therapy for a range of cancer diagnoses. ResultsThe preliminary main results are the following. There were 382 ED presentations of chemotherapy related FN in cancer patients and a sample of 170 were selected in regards to a 30-day frame between the FN episode and the chemotherapy administration. The most common diagnoses were breast (33/170; 19.4%); bowel (32/170; 18.8%) and genitourinary cancers (30/170; 17.6%). A total of 145 (145/170; 85.2%) were given a triage level III and the rest (25/170; 14.7%) a triage level II. ConclusionsThere is still some important data to exploit such as median time from triage to medical attention and median time from triage to antibiotic, which will allow the researchers to establish the percentage of compliance with evidence based guidelines. As reported in international literature the compliance is challenging in a busy and unpredictable ED setting. Therefore it will be interesting to measure our compliance rates and explore opportunities to further improve adherence to evidence-based guidelines and aim for better clinical outcomes in case our results correlate with current literature. Legal entity responsible for the studyEthic Committee Hospital Clinic Barcelona. FundingHas not received any funding. DisclosureThe author has declared no conflicts of interest.