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Joan Llach, Sabela Carballal, Leticia Moreira Departmento de Gastroenterología, Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d’ Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Universidad de Barcelona, Barcelona, SpainCorrespondence: Leticia Moreira Villarroel 170, Barcelona 08036, SpainTel +34 932275400Fax +34 932279381Email lmoreira@clinic.catAbstract: Pancreatic cancer (PC) is a highly lethal disease, mostly incurable when detected. Thus, despite advances in PC treatments, only around 7% of patients survive 5-years after diagnosis. This morbid outcome is secondary to multifactorial reasons, such as late-stage diagnosis, rapid progression and minimal response to chemotherapy. Based on these factors, it is of special relevance to identify PC high-risk individuals in order to establish preventive and early detection measures. Although most PC are sporadic, approximately 10% cases have a familial basis. No main causative gene of PC has been identified but several known germline pathogenic mutations are related with an increased risk of this tumor. These inherited cancer syndromes represent 3% of all PC. On the other hand, in 7% of cases of PC, there is a strong family history without a causative germline mutation, a situation known as familial pancreatic cancer (FPC). In recent years, there is increasing evidence supporting the benefit of genetic germline analysis in PC patients, and periodic pancreatic screening in PC high-risk patients (mainly those with a lifetime risk greater than 5%), although there is no general agreement in the group of patients and individuals to study and screen. In the present review, we expose an update in the field of hereditary and FPC, with the aim of describing the current strategies and implications in genetic counseling, surveillance and therapeutic interventions.Keywords: pancreatic cancer, hereditary, familial, mutation, screening, personalized medicine

Maria Liz Leoz, Sabela Carballal, Leticia Moreira, Teresa Ocaña, Francesc Balaguer Department of Gastroenterology, Hospital Clínic, Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas (CIBERehd), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain Abstract: Familial adenomatous polyposis (FAP) is an inherited disorder that represents the most common gastrointestinal polyposis syndrome. Germline mutations in the APC gene were initially identified as responsible for FAP, and later, several studies have also implicated the MUTYH gene as responsible for this disease, usually referred to as MUTYH-associated polyposis (MAP). FAP and MAP are characterized by the early onset of multiple adenomatous colorectal polyps, a high lifetime risk of colorectal cancer (CRC), and in some patients the development of extracolonic manifestations. The goal of colorectal management in these patients is to prevent CRC mortality through endoscopic and surgical approaches. Individuals with FAP and their relatives should receive appropriate genetic counseling and join surveillance programs when indicated. This review is focused on the description of the main clinical and genetic aspects of FAP associated with germline APC mutations and MAP. Keywords: colorectal cancer, familial adenomatous polyposis, MAP, APC, MUTYH

Assessment of the anatomical colorectal segment of polyps during colonoscopy is important for treatment and follow-up strategies, but is largely operator dependent. This feasibility study aimed to assess whether, using images of a magnetic endoscope imaging (MEI) positioning device, a deep learning approach can be useful to objectively divide the colorectum into anatomical segments. Models based on the VGG-16 based convolutional neural network architecture were developed to classify the colorectum into anatomical segments. These models were pre-trained on ImageNet data and further trained using prospectively collected data of the POLAR study in which endoscopists were using MEI (3930 still images and 90,151 video frames). Five-fold cross validation with multiple runs was used to evaluate the overall diagnostic accuracies of the models for colorectal segment classification (divided into a 5-class and 2-class colorectal segment division). The colorectal segment assignment by endoscopists was used as the reference standard. For the 5-class colorectal segment division, the best performing model correctly classified the colorectal segment in 753 of the 1196 polyps, corresponding to an overall accuracy of 63%, sensitivity of 63%, specificity of 89% and kappa of 0.47. For the 2-class colorectal segment division, 1112 of the 1196 polyps were correctly classified, corresponding to an accuracy of 93%, sensitivity of 93%, specificity of 90% and kappa of 0.82. The diagnostic performance of a deep learning approach for colorectal segment classification based on images of a MEI device is yet suboptimal (clinicaltrials.gov: NCT03822390). [ABSTRACT FROM AUTHOR]

Nirsevimab has been recently licensed for universal RSV prophylaxis in infants. NIRSE-GAL is a three-year population-based study initiated in Galicia in September 2023. It aims to evaluate nirsevimab effectiveness against RSV-related hospitalizations lower respiratory tract infections (LRTI), severe RSV, all-cause LRTI, and all-cause hospitalization. NIRSE-GAL also aims to estimate nirsevimab impact on primary healthcare use in the short and mid-term, children's wheezing and asthma, and medical prescriptions for RSV. The immunization campaigns will be scheduled based on the expected start week for the RSV season and will last the whole season. Immunization will be offered to: i) infants born during the campaign (seasonal), ii) infants < 6 months at the start of the campaign (catch-up), and iii) infants with high-risk factors, aged 6-24 months at the start of the campaign (high-risk). The follow-up period will start: i) the immunization date for all immunized infants, ii) the start of the campaign, for the non-immunized catch-up or high-risk groups, or iii) the birthdate for the non-immunized seasonal group. Infants will be followed up until outcome occurrence, death, or end of study. Nirsevimab effectiveness will be estimated using Poisson and Cox regression models. Sensitivity and stratified analyses will be undertaken. The number of averted cases and the number needed to immunize will be estimated. Immunization failure and nirsevimab safety will be monitored. NIRSE-GAL was approved by the ethics committee of Galicia (CEIC 2023-377) and registered in ClinicalTrials.gov (ID: NCT06180993). Findings will be mainly shared via peer-reviewed publications and scientific conferences.

Background: Galicia (Spain) was one of the first regions worldwide to incorporate nirsevimab for universal respiratory syncytial virus (RSV) prophylaxis in infants into its immunisation programme. The NIRSE-GAL longitudinal population-based study aimed to assess nirsevimab effectiveness in preventing hospitalisations (ie, admittance to hospital)., Methods: The 2023-24 immunisation campaign with nirsevimab in Galicia began on Sept 25, 2023, and concluded on March 31, 2024. The campaign targeted three groups: infants born during the campaign (seasonal group), infants younger than 6 months at the start of the campaign (catch-up group), and infants aged 6-24 months with high-risk factors at the start of the campaign (high-risk group). Infants in the seasonal group were offered immunisation on the first day of life before discharge from hospital. Infants in the catch-up and high-risk groups received electronic appointments to attend a public hospital or health-care centre for nirsevimab administration. For this interim analysis, we used data collected from Sept 25 to Dec 31, 2023, from children born up to Dec 15, 2023. Data were retrieved from public health registries. Nirsevimab effectiveness in preventing RSV-associated lower respiratory tract infection (LRTI) hospitalisations; severe RSV-related LRTI requiring intensive care unit admission, mechanical ventilation, or oxygen support; all-cause LRTI hospitalisations; and all-cause hospitalisations was estimated using adjusted Poisson regression models. Data from five past RSV seasons (2016-17, 2017-18, 2018-19, 2019-20, and 2022-23), excluding the COVID-19 pandemic period, were used to estimate the number of RSV-related LRTI hospitalisations averted along with its IQR. The number needed to immunise to avoid one case in the 2023-24 season was then estimated from the averted cases. Nirsevimab safety was routinely monitored. The NIRSE-GAL study protocol was registered on ClinicalTrials.gov (NCT06180993), and follow-up of participants is ongoing., Findings: 9408 (91·7%) of 10 259 eligible infants in the seasonal and catch-up groups received nirsevimab, including 6220 (89·9%) of 6919 in the catch-up group and 3188 (95·4%) of 3340 in the seasonal group. 360 in the high-risk group were offered nirsevimab, 348 (97%) of whom received it. Only infants in the seasonal and catch-up groups were included in analyses to estimate nirsevimab effectiveness and impact because there were too few events in the high-risk group. In the catch-up and seasonal groups combined, 30 (0·3%) of 9408 infants who received nirsevimab and 16 (1·9%) of 851 who did not receive nirsevimab were hospitalised for RSV-related LRTI, corresponding to an effectiveness of 82·0% (95% CI 65·6-90·2). Effectiveness was 86·9% (69·1-94·2) against severe RSV-related LRTI requiring oxygen support, 69·2% (55·9-78·0) against all-cause LRTI hospitalisations, and 66·2% (56·0-73·7) against all-cause hospitalisations. Nirsevimab effectiveness against other endpoints of severe RSV-related LRTI could not be estimated because of too few events. RSV-related LRTI hospitalisations were reduced by 89·8% (IQR 87·5-90·3), and the number needed to immunise to avoid one RSV-related LRTI hospitalisation was 25 (IQR 24-32). No severe adverse events related to nirsevimab were registered., Interpretation: Nirsevimab substantially reduced infant hospitalisations for RSV-associated LRTI, severe RSV-associated LRTI requiring oxygen, and all-cause LRTI when given in real-world conditions. These findings offer policy makers and health authorities robust, real-world, population-based evidence to guide the development of strategies for RSV prevention., Funding: Sanofi and AstraZeneca., Translation: For the Spanish translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests FM-T reports having acted as principal investigator in randomised controlled trials for Ablynx, Abbott, Seqirus, Sanofi Pasteur, Cubist, Wyeth, Merck, Pfizer, Roche, Regeneron, Jansen, Medimmune, Novavax, Novartis, and GSK, with honoraria paid to his institution and relationships with GSK Vaccines, Pfizer, Sanofi Pasteur, Janssen Pharmaceuticals, MSD, and Seqirus that include consulting or advisory roles. RK, JJ, and LP-A are Sanofi employees and hold shares or stock options in the company. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background and Aims: The adenoma detection rate (ADR), recognized as a surrogate marker for colorectal cancer (CRC) incidence and mortality reduction, is closely linked to the efficacy of bowel cleansing. However, there is a dearth of evidence examining the impact on ADR when using 2 distinct very-low-dose bowel cleansing products. This study sought to compare ADR in an immunochemical fecal occult blood test (iFOBT)-based organized screening program by using 1 L of polyethylene glycol plus ascorbate (1L-PEGA) versus sodium picosulfate with magnesium citrate (SPMC), both administered in a split-dose regimen., Methods: We conducted a comparative, parallel, randomized, noninferiority, and low-intervention clinical trial targeting individuals from a population CRC screening program aged 50 to 69 years with a positive iFOBT result scheduled for a workup colonoscopy in the morning. Participants were randomized to either 1L-PEGA or SPMC for bowel cleansing. The main outcome was ADR, whereas secondary outcomes were bowel preparation quality, safety, tolerability, and satisfaction., Results: A total of 1002 subjects, 501 were included in each group. There were no differences between groups with respect to pooled ADR (SPMC, 56.5% [95% CI, 52.1-60.8]; 1L-PEGA, 53.7% [95% CI, 49.3-58.0]; relative risk, .95 [95% CI, .85-1.06]); therefore, SPMC demonstrated noninferiority in ADR compared with 1L-PEGA (difference, 2.8%; 2-sided 95% lower confidence limit, -3.4). In addition, there were no significant differences in mean lesions regardless of size and location between arms. Bowel preparation favored 1L-PEGA (96.2% vs 89.2%, P < .001), whereas SPMC exhibited significantly higher safety and tolerability, as shown by fewer nonserious treatment-emergent adverse events., Conclusions: SPMC emerged as a noninferior laxative compared with 1L-PEGA concerning ADR. Despite the superior bowel preparation quality associated with 1L-PEGA, the safety, tolerability, and overall satisfaction of participants were higher with SPMC. (Clinical trial registration number: EudraCT: 2019-003186-18.)., Competing Interests: Disclosure The following authors disclosed financial relationships: A. Serradesanferm: Research support from Beca d’Intensificació Clínic. R. Moreira: Research support from Programa d'impuls del talent i de l'ocupabilitat del PERIS 2016-2020, Generalitat de Catalunya, Departament de Salut, SLT017/20/000179. A. Castells: Research support from Fundación Científica de la Asociación Española contra el Cáncer and Universal Diagnostics; consultant for Goodgut, Amadix, and iVascular; speaker for Medial EarlySign and Abbvie. M. Pellisé: Research support from Fujifilm Spain, ZiuZ, and Casen Recordati; speaker for Fujifilm, Olympus, Medtronic, Norgine, Alphasigma, Mayoli, and Casen Recordati. All other authors disclosed no financial relationships. Research support for this study was provided by Casen Recordati. Research support for this study was provided by Casen Recordati, S.L., Spain., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: The morbidity burden of respiratory syncytial virus (RSV) in infants extends beyond hospitalization. Defining the RSV burden before implementing prophylaxis programs is essential for evaluating any potential impact on short- to mid-term morbidity and the utilization of primary healthcare (PHC) and emergency services (ES). We established this reference data using a population-based cohort approach., Methods: Infants hospitalized for RSV from January 2016 to March 2023 were matched with non-hospitalized ones based on birthdate and sex. We defined the exposure as severe RSV hospitalization. The main study outcomes were as follows: (1) PHC and ES visits for RSV, categorized using the International Classification of Primary Care codes, (2) prescriptions for respiratory airway obstructive disease, and (3) antibacterial prescriptions. Participants were followed up from 30 days before hospitalization for severe RSV until the outcome occurrence or end of the study. Adjusted incidence rate ratios (IRRs) of the outcomes along with their 95% confidence intervals (CI) were estimated using Poisson regression models. Stratified analyses by type of PHC visit (nurse, pediatrician, or pharmacy) and follow-up period were undertaken. We defined mid-term outcomes as those taking place up to 24 months of follow-up period., Results: The study included 6626 children (3313 RSV-hospitalized; 3313 non-hospitalized) with a median follow-up of 53.7 months (IQR = 27.9, 69.4). After a 3-month follow-up, severe RSV was associated with a considerable increase in PHC visits for wheezing/asthma (IRR = 4.31, 95% CI: 3.84-4.84), lower respiratory infections (IRR = 4.91, 95% CI: 4.34-5.58), and bronchiolitis (IRR = 4.68, 95% CI: 2.93-7.65). Severe RSV was also associated with more PHC visits for the pediatrician (IRR = 2.00, 95% CI: 1.96-2.05), nurse (IRR = 1.89, 95% CI: 1.75-1.92), hospital emergency (IRR = 2.39, 95% CI: 2.17-2.63), primary healthcare emergency (IRR: 1.54, 95% CI: 1.31-1.82), as well as with important increase in prescriptions for obstructive airway diseases (IRR = 5.98, 95% CI: 5.43-6.60) and antibacterials (IRR = 4.02, 95% CI: 3.38-4.81). All findings remained substantial until 2 years of post-infection., Conclusions: Severe RSV infection in infants significantly increases short- to mid-term respiratory morbidity leading to an escalation in healthcare utilization (PHC/ES attendance) and medication prescriptions for up to 2 years afterward. Our approach could be useful in assessing the impact and cost-effectiveness of RSV prevention programs., (© 2024 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background and Objectives: There are few scales with prospective validation for the assessment of the upper gastrointestinal mucosal cleanliness during an esophagogastroduodenoscopy (EGD). The aim of this study was to develop a valid and reproducible cleanliness scale for use during an EGD., Methods: We developed a cleanliness scale (Barcelona scale) with a score (0-2 points) of five segments of the upper gastrointestinal tract with thorough cleaning techniques (esophagus, fundus, body, antrum, and duodenum). First, 125 photos (25 of each area) were assessed, and a score was assigned to each image by consensus among 7 experts endoscopists. Subsequently, 100 of the 125 images were selected and the inter- and intra-observer variability of 15 previously trained endoscopists was evaluated using the same images at two different times., Results: In total, 1500 assessments were performed. In 1336/1500 observations (89%) there was agreement with the consensus score, with a mean kappa value of 0.83 (0.45-0.96). In the second evaluation, in 1330/1500 observations (89%) there was agreement with the consensus score, with a mean kappa value of 0.82 (0.45-0.93). The intra-observer variability was 0.89 (0.76-0.99)., Conclusions: The Barcelona cleanliness scale is a valid measure and reproducible with minimal training. Its application in clinical practice is a significant step to standardize the quality of the EGD., (Copyright © 2023 Elsevier España, S.L.U. All rights reserved.)

While clinical practice guidelines for hereditary diffuse gastric cancer are well established, there is no consensus on the approach for familial intestinal gastric cancer (FIGC). In low-incidence gastric cancer (GC) areas such as the United States or most European countries, there are no evidence-based recommendations on endoscopic assessment in FIGC families. We aim to describe the yield of GC surveillance in these families, and to identify epidemiological risk factors for the development of GC and its precursor lesions. This is a multicenter observational study involving nine tertiary Spanish hospitals, in which all individuals fulfilling FIGC criteria who underwent endoscopic surveillance were included between 1991 and 2020. Forty-one healthy individuals of 31 families were recruited. The median number of upper gastrointestinal endoscopies per individual was 3 (interquartile range, IQR, 1-4). The median interval time between tests was 2 years (IQR 1.5-2.5), and the median follow-up was 9 years (IQR 3-14.5). In 18 (43.9%) subjects, a precursor lesion of GC was found during follow-up, and in 2 (4.9%), an early GC was identified, in which curative treatment was offered. Helicobacter pylori (Hp) infection proved to be independently associated with an increased risk of developing precursor lesions or GC, adjusted by age, gender and follow-up, with an Odds Ratio of 6.443 (1.36-30.6, P value .019). We present the first outcomes that support endoscopic surveillance with biopsies and detection of Hp in FIGC families, although the periodicity has yet to be defined., (© 2023 UICC.)

A monoclonal antibody for universal respiratory syncytial virus prophylaxis in infants has recently been licensed. We share our experiences of integrating nirsevimab into the regional immunisation programme in Galicia, Spain. After a 3-week hospital-based immunisation campaign with flexible individualised appointments and educational activities, nirsevimab uptake was 97.5% in the high-risk group, 81.4% in the catch-up group and 92.6% in infants born during the campaign. This successful implementation strategy can serve as a model and may inform other countries' programmatic deliberations.

Background: Studies on vaccine effectiveness (VE) against COVID-19 in the pediatric population are outgoing. We aimed to quantify VE against SARS-CoV-2 in two pediatric age groups, 5-11 and 12-17-year-old, while considering vaccine type, SARS-CoV-2 variant, and duration of protection., Methods: A population-based test-negative control study was undertaken in Galicia, Spain. Children 5-11-year-old received the Comirnaty® (Pfizer, US) vaccine, while those aged 12-17-year-old received the Comirnaty® (Pfizer, US) or SpikeVax® (ModernaTX, Inc) vaccine. Participants were categorized into unvaccinated (0 doses or one dose with <14 days since vaccination), partially vaccinated (only one dose with ≥14 days, or two doses with <14 days after the second dose administration), and fully vaccinated (two doses with ≥14 days after the second injection). Adjusted odds ratios (OR) and their 95% confidence intervals (CI) were estimated using multiple logistic regression models. VE was calculated as (1-OR) * 100. Stratified and sensitivity analyses were performed., Results: In the fully vaccinated 5-11-year-old children, VE against the Omicron variant was 44.1% (95% CI: 38.2%-49.4%). In the fully vaccinated 12-17-year-old individuals, VE was 83.4% (95% CI: 81.2%-85.3%) against Delta and 74.8% (95% CI: 58.5%-84.9%) against Omicron. Comirnaty® and SpikeVax® vaccines showed a similar magnitude of VE against Delta [Comirnaty® VE: 81.9% (95% CI: 79.3%-84.1%) and SpikeVax® VE: 85.3% (95% CI: 81.9%-88.1%)]. Comirnaty® (Pfizer, US; VE: 79.7%; 95% CI: 50.7%-92.4%) showed a slightly higher magnitude of protection against Omicron than SpikeVax® (ModernaTX, Inc), yet with an overlapping CI (VE: 74.3%; 95% CI: 56.6%-84.9%). VE was maintained in all age subgroups in both pediatric populations, but it declined over time., Conclusions: In Galicia, mRNA VE was moderate against SARS-CoV-2 infections in the 5-11-year-old populations, but high in older children. VE declined over time, suggesting a potential need for booster dose schedules., (© 2023 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Patients with serrated polyposis syndrome (SPS) have multiple and/or large serrated colonic polyps and higher risk for colorectal cancer. SPS inherited genetic basis is mostly unknown. We aimed to identify new germline predisposition factors for SPS by functionally evaluating a candidate gene and replicating it in additional SPS cohorts., Methods: After a previous whole-exome sequencing in 39 SPS patients from 16 families (discovery cohort), we sequenced specific genes in an independent validation cohort of 211 unrelated SPS cases. Additional external replication was also available in 297 SPS cases. The WNK2 gene was disrupted in HT-29 cells by gene editing, and WNK2 variants were transfected using a lentiviral delivery system. Cells were analysed by immunoblots, real-time PCR and functional assays monitoring the mitogen-activated protein kinase (MAPK) pathway, cell cycle progression, survival and adhesion., Results: We identified 2 rare germline variants in the WNK2 gene in the discovery cohort, 3 additional variants in the validation cohort and 10 other variants in the external cohorts. Variants c.2105C>T (p.Pro702Leu), c.4820C>T (p.Ala1607Val) and c.6157G>A (p.Val2053Ile) were functionally characterised, displaying higher levels of phospho-PAK1/2, phospho-ERK1/2, CCND1, clonogenic capacity and MMP2., Conclusion: After whole-exome sequencing in SPS cases with familial aggregation and replication of results in additional cohorts, we identified rare germline variants in the WNK2 gene. Functional studies suggested germline WNK2 variants affect protein function in the context of the MAPK pathway, a molecular hallmark in this disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Three percent of patients with pancreatic ductal adenocarcinoma (PDAC) present a germline pathogenic variant (GPV) associated with an increased risk of this tumor, CDKN2A being one of the genes associated with the highest risk. There is no clear consensus on the recommendations for surveillance in CDKN2A GPV carriers, although the latest guidelines from the International Cancer of the Pancreas Screening Consortium recommend annual endoscopic ultrasound (EUS) or magnetic resonance imaging (MRI) regardless of family history. Our aim is to describe the findings of the PDAC surveillance program in a cohort of healthy CDKN2A GPV heterozygotes. This is an observational analysis of prospectively collected data from all CDKN2A carriers who underwent screening for PDAC at the high-risk digestive cancer clinic of the "Hospital Clínic de Barcelona" between 2013 and 2021. A total of 78 subjects were included. EUS or MRI was performed annually with a median follow-up of 66 months. Up to 17 pancreatic findings were described in 16 (20.5%) individuals under surveillance, although most of them were benign. No significant precursor lesions were identified, but an early PDAC was detected and treated. While better preventive strategies are developed, we believe that annual surveillance with EUS and/or MRI in CDKN2A GPV heterozygotes may be beneficial.

Serrated polyposis syndrome (SPS) is one of the most frequent polyposis syndromes characterized by an increased risk for developing colorectal cancer (CRC). Although SPS etiology has been mainly associated with environmental factors, germline predisposition to SPS could also be relevant for cases with familial aggregation or a family history of SPS/CRC. After whole-exome sequencing of 39 SPS patients from 16 families, we identified a heterozygous germline frameshift variant in the POLD1 gene (c.1941delG, p.(Lys648fs*46)) in a patient with SPS and CRC. Tumor presented an ultra-hypermutated phenotype and microsatellite instability. The POLD1 germline variant segregated in three additional SPS-affected family members. We attempted to create yeast and cellular models for this variant but were no viable. Alternatively, we generated patient-derived organoids (PDOs) from healthy rectal tissue of the index case, as well as from a control donor. Then, we challenged PDOs with a DNA-damaging agent to induce replication stress. No significant differences were observed in the DNA damage response between control and POLD1 -Lys648fs PDOs, nor specific mutational signatures were observed. Our results do not support the pathogenicity of the analyzed POLD1 frameshift variant. One possible explanation is that haplosufficiency of the wild-type allele may be compensating for the absence of expression of the frameshift allele. Overall, future work is required to elucidate if functional consequences could be derived from POLD1 alterations different from missense variants in their proofreading domain. To our knowledge, our study presents the first organoid model for germline POLD1 variants and establishes the basis for its use as a model for disease in SPS, CRC and other malignancies., Competing Interests: LA is a compensated consultant and has equity interest in io9, LLC. His spouse is an employee of Biotheranostics, Inc. LA is an inventor of a U.S. Patent 10,776,718 and he also declares U.S. provisional patent applications with serial numbers: 63/289,601, 63/269,033, 63/412,835, 63/366,392, and 63/367,846. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bonjoch, Soares de Lima, Díaz-Gay, Dotti, Muñoz, Moreira, Carballal, Ocaña, Cuatrecasas, Ortiz, Castells, Pellisé, Balaguer, Salas, Alexandrov and Castellví-Bel.)

Background: Research on the effectiveness of COVID-19 booster-based vaccine schedule is ongoing and real-world data on vaccine effectiveness (VE) in comorbid patients are limited. We aimed to estimate booster dose VE against SARS-CoV-2 infection and COVID-19 severity in the general population and in comorbid patients., Method: A retrospective test-negative control study was undertaken in Galicia-Spain (December 2020-November 2021). VE and 95% confidence interval (CI) were estimated using multivariate logistic regression models., Results: 1,512,415 (94.13%) negative and 94,334 (5.87%) positive SARS-CoV-2 test results were included. A booster dose of COVID-19 vaccine is associated with substantially higher protection against SARS-CoV-2 infection than vaccination without a booster [VE boosted  = 87% (95%CI: 83%; 89%); VE non-boosted  = 66% (95%CI: 65%; 67%)]. The high VE was observed in all ages, but was more pronounced in subjects older than 65 years. VE against COVID-19 severity was analyzed in a mixed population of boosted and non-boosted individuals and considerable protection was obtained [VE: hospitalization = 72% (95%CI: 68%; 75%); intensive care unit administration = 83% (95%CI: 78%; 88%), in-hospital mortality = 66% (95%CI: 53%; 75%)]. Boosted comorbid patients are more protected against SARS-CoV-2 infection than those who were non-boosted. This was observed in a wide range of major diseases including cancer (81% versus 54%), chronic obstructive pulmonary disease (84% versus 61%), diabetes (84% versus 65%), hypertension (82% versus 65%) and obesity (91% versus 67%), among others., Conclusions: A booster dose of COVID-19 vaccine increases the protection against SARS-CoV-2 infection and COVID-19 severity in the general population and in comorbid patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and study aims  Artificial intelligence is currently able to accurately predict the histology of colorectal polyps. However, systems developed to date use complex optical technologies and have not been tested in vivo. The objective of this study was to evaluate the efficacy of a new deep learning-based optical diagnosis system, ATENEA, in a real clinical setting using only high-definition white light endoscopy (WLE) and to compare its performance with endoscopists. Methods  ATENEA was prospectively tested in real life on consecutive polyps detected in colorectal cancer screening colonoscopies at Hospital Clínic. No images were discarded, and only WLE was used. The in vivo ATENEA's prediction (adenoma vs non-adenoma) was compared with the prediction of four staff endoscopists without specific training in optical diagnosis for the study purposes. Endoscopists were blind to the ATENEA output. Histology was the gold standard. Results  Ninety polyps (median size: 5 mm, range: 2-25) from 31 patients were included of which 69 (76.7 %) were adenomas. ATENEA correctly predicted the histology in 63 of 69 (91.3 %, 95 % CI: 82 %-97 %) adenomas and 12 of 21 (57.1 %, 95 % CI: 34 %-78 %) non-adenomas while endoscopists made correct predictions in 52 of 69 (75.4 %, 95 % CI: 60 %-85 %) and 20 of 21 (95.2 %, 95 % CI: 76 %-100 %), respectively. The global accuracy was 83.3 % (95 % CI: 74%-90 %) and 80 % (95 % CI: 70 %-88 %) for ATENEA and endoscopists, respectively. Conclusion  ATENEA can accurately be used for in vivo characterization of colorectal polyps, enabling the endoscopist to make direct decisions. ATENEA showed a global accuracy similar to that of endoscopists despite an unsatisfactory performance for non-adenomatous lesions., Competing Interests: Competing interests Glòria Fernández-Esparrach was employed on an advisory board of Medtronic and is shareholder of MiWEndo Solutions S.L. Míriam Cuatrecases is shareholder of MiWEndo Solutions S.L. Maria Pellisé has served on clinical advisory boards for Fujifilm Europe; has served on the clinical advisory board and owns share options in MiWendo S.L.; reports speaker fees from Casen Recordati, Fujifilm, Medtronic and Olympus Europe; and has received research funding from Fujifilm Europe, Casen Recordati and Ziuz., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

BACKGROUND : Current guidelines recommend genetic counseling and intensive colonoscopy surveillance for patients with ≥ 10 colorectal adenomas based on scarce data. We investigated the prevalence of this condition in a fecal immunochemical test (FIT)-based colorectal (CRC) screening program, and the incidence of metachronous lesions during follow-up., Methods: We retrospectively included all FIT-positive participants with ≥ 10 adenomas at index colonoscopy between 2010 and 2018. Surveillance colonoscopies were collected until 2019. Patients with inherited syndromes, serrated polyposis syndrome, total colectomy, or lacking surveillance data were excluded. The cumulative incidence of CRC and advanced neoplasia were analyzed by Kaplan-Meier analysis. Risk factors for metachronous advanced neoplasia were investigated by multivariable logistic regression analysis., Results: 215 of 9582 participants (2.2 %) had ≥ 10 adenomas. Germline genetic testing was performed in 92 % of patients with ≥ 20 adenomas, identifying two inherited syndromes (3.3 %). The 3-year cumulative incidence of CRC and advanced neoplasia were 1 % and 16 %, respectively. In 39 patients (24.2 %), no polyps were found on first surveillance colonoscopy. The presence of an advanced adenoma was independently associated with a higher risk of advanced neoplasia at first surveillance colonoscopy (odds ratio 3.91, 95 %CI 1.12-13.62; P  = 0.03). Beyond the first surveillance colonoscopy, the risk of metachronous advanced neoplasia was lower., Conclusions: The prevalence of ≥ 10 adenomas in a FIT-based CRC screening program was 2.2 %; a small proportion of inherited syndromes were detected, even amongst those with ≥ 20 adenomas. A low rate of post-colonoscopy CRC was observed and the risk of advanced neoplasia beyond the first surveillance colonoscopy tended to progressively decrease throughout successive follow-ups., Competing Interests: FB received endoscopic equipment on loan of Fujifilm, received an honorarium for consultancy from Sysmex (2017–2020) and CPP-FAP (2018), speaker’s fee from Norgine Iberia, and editorial fee from Elsevier as editor of Gastroenterologia y Hepatologia. M. Pellisé has received consultancy and speaker’s fees from Norgine Iberia (2015–2020), a consultancy fee from GI Supply (2019), speaker’s fees from Casen Recordati (2016–2019), Olympus (2018), and Jansen (2018), and research funding from Fujifilm Spain (2019), Fujifilm Europe (2020), and Casen Recordati (2020); her department has received loan material from Fujifilm Spain (from 2017 ongoing), a research grant from Olympus Europe (2005–2019), and loan material and a research grant from Fujifilm Europe (2020–2021); she is a Board member of ESGE and SEED; and receives a fee from Thieme as an Endoscopy Co-Editor., (Thieme. All rights reserved.)