Long-term Health Outcomes After Hospital Discharge Among Children Hospitalized for MIS-C or COVID-19, September 29, 2021, to June 21, 2022.

BACKGROUND: The long-term effects of children hospitalized with multisystem inflammatory syndrome in children (MIS-C) or acute COVID-19 are not well known. Our objective was to determine long-term outcomes. METHODS: Children hospitalized with MIS-C or COVID-19 at 3 US hospitals from March 2020, through February 2021 were followed to assess health through 2 years post-hospitalization using medical records and patient surveys. RESULTS: Medical record abstraction was performed for 183 patients hospitalized with MIS-C, 53 of whom participated in surveys, and 97 patients hospitalized with COVID-19, 35 of whom participated in surveys. Patients with MIS-C were younger (median, 9 vs. 14 years of age for COVID-19 patients; P = 0.004), more frequently male (62% vs. 39%; P < 0.001) and had more cardiac (14% vs. 2%; P = 0.001) and neurologic sequelae (8% vs. 1%; P = 0.023). Children with COVID-19 more often had other comorbidities (59% vs. 19%; P < 0.001). Full mental recovery at the time of survey 2 (median, 16 months post-hospitalization for patients with MIS-C and 20 months for patients with COVID-19) was 85% and 88%, respectively; full physical recovery was 87% and 81%, respectively; and nearly all had resumption of normal activities. Patients with MIS-C reported more frequent headache at 1 month (45% vs. 20%; P = 0.037). Patients with COVID-19 were more likely to report cough at 1 month (37% vs. 17%; P = 0.045). Fatigue persisted >1 year in 15%-20% of patients in both groups. CONCLUSIONS: Approximately 20% of children with MIS-C and COVID-19 continued to have symptoms including fatigue and headache >1 year after hospital discharge. The duration of these findings emphasizes the importance of providers following patients until sequelae have resolved.

Musicianship and prominence of inter-hemispheric connectivity determine two different pathways to atypical language dominance.

During infancy and adolescence, language develops from a predominantly inter-hemispheric control - through the corpus callosum - to a predominantly intra-hemispheric control - mainly subserved by the left arcuate fasciculus. Using multimodal neuroimaging, we demonstrate that human left-handers (both male and female) with an atypical language lateralization show a rightward participation of language areas from auditory cortex to inferior frontal cortex when contrasting speech to tones perception, and an enhanced inter-hemispheric anatomical and functional connectivity. Crucially, musicianship determines two different structural pathways to this outcome. Non-musicians present a relation between atypical lateralization and intra-hemispheric underdevelopment across the anterior arcuate fasciculi, hinting at a dysregulation of the ontogenetic shift from an inter-hemispheric to an intra-hemispheric brain. Musicians reveal an alternative pathway related to inter-hemispheric overdevelopment across the posterior corpus callosum and the auditory cortex. We discuss the heterogeneity in reaching atypical language lateralization and the relevance of early musical training in altering the normal development of language cognitive functions.Significance statement Since the discovery in the 19th century that left-handedness predisposes to an atypical lateralization of language, progress in understanding how this condition appears in healthy individuals has been scarce. Here, we introduce a new relevant factor: musical training. We demonstrate how this early and intensive audiomotor learning can potentially modify the hemispheric specialization of language by prompting a differential development of the callosal fibers. Importantly, this perspective also reveals an alternative route to atypical lateralization - unrelated to musicianship - through an underdevelopment of the arcuate fasciculi. In both scenarios, interhemispheric connectivity through the callosum remains prominent, directly or indirectly. Therefore, the historical lack of definitive answers to this phenomenon might be attributed to the existence of multiple potential pathways.

Rhabdomyolysis in Acute HIV Infection.

Rhabdomyolysis is a rare but potentially life-threatening complication of acute HIV infection. We present a case report of a young adult male who presented with fever, myalgia, and elevated creatine phosphokinase levels, ultimately diagnosed with acute HIV infection-associated rhabdomyolysis. This case highlights the importance of considering HIV infection in the differential diagnosis of rhabdomyolysis, particularly in at-risk populations, even in the absence of typical HIV-related symptoms.

Yoga in Pediatric Gastroenterology.

PURPOSE OF REVIEW: Pediatric use of yoga as an integrative medicine modality has increased in prevalence over the last several decades. In this article, we review the available evidence for yoga in pediatric gastrointestinal disorders. RECENT FINDINGS: Evidence supports that in many pediatric disorders of gut brain interaction (DGBI), including irritable bowel syndrome, functional abdominal pain and functional dyspepsia, yoga decreases pain intensity and frequency and increases school attendance. Yoga has been shown to improve health-related quality of life and improve stress management as an effective adjunct to standard medical therapy in pediatric inflammatory bowel disease (IBD). Further studies are needed regarding optimal frequency, duration of practice and evaluation of the impact on IBD disease activity measures. Yoga may benefit pediatric gastroenterology patients with DGBIs and IBD through improving quality of life and reducing pain. Future yoga studies could investigate biomarkers and continued research will help integrate this modality into routine pediatric gastroenterology care.

Measurement invariance of the Intuitive Eating Scale-2 across country, ethnicity, sex, and sexual orientation: A cross-cultural study between Brazil and the U.S.

Intuitive eating is defined as being connected to internal hunger, satiety, and appetitive cues and flexibly using these cues to determine when, what, and how much to eat. The Intuitive Eating Scale-2 (IES-2) is a widely used measure of facets of intuitive eating. However, the scale has shown unstable factor structure in several validation studies and there is a lack of studies investigating the measurement invariance of the IES-2 beyond sex. We aimed to evaluate the psychometric properties of the IES-2, testing several factor structures among Brazilian and U.S. samples of men and women; to test measurement invariance across country of origin, ethnicity, sex, and sexual orientation; and to evaluate its internal consistency. Three models of the latent structure of the IES-2 were tested using confirmatory factor analyses (CFA) in a total of 1072 young adults (452 Brazilians and 620 Americans), aged 18-35 years. Results demonstrated that only a 3-factor solution with 11 items of the IES-2 showed adequate fit to the data for both countries. This model demonstrated scalar invariance across sex and sexual orientation, but only configural invariance was found across country of origin and ethnicity. Good internal consistencies were found for both the Brazilian and American samples. The present study provides support for a 3-factor solution with 11 items of the IES-2, to Brazilian and American samples. The study also offers evidence of internal consistency, and invariance between sex (i.e., male and female) and sexual orientation (i.e., heterosexual participants and sexual minority participants).

Temporal assessment of Gross alpha emissions from the petroleum industry in Tenerife, Canary Islands (2001-2022).

A ca. 76% decrease in gross alpha activity levels, measured in surface aerosols collected in the city of Santa Cruz de Tenerife (Spain), has been explained in the present study in connection with the reduction of activities, and eventual closure, of an oil refinery in the city. Gross Alpha in surface aerosols, collected at weekly intervals over a period of 22 years (2001-2022), was used for the analysis. The dynamic behaviour of the gross alpha time series was studied using statistical wavelet, multifractal analysis, empirical decomposition method, multivariate analysis, principal component, and cluster analyses approaches. This was performed to separate the impact of other sources of alpha emitting radionuclides influencing the gross alpha levels at this site. These in-depth analyses revealed a noteworthy shift in the dynamic behaviour of the gross alpha levels following the refinery's closure in 2013. This analysis also attributed fluctuations and trends in the gross alpha levels to factors such as the 2008 global economic crisis and the refinery's gradual reduction of activity leading up to its closure. The mixed-model approach, incorporating multivariate regression and autoregressive integrated moving average methods, explained approximately 84% of the variance of the gross alpha levels. Finally, this work underscored the marked reduction in alpha activity levels following the refinery's closure, alongside the decline of other pollutants (CO, SO2, NO, NO2, Benzene, Toluene and Xylene) linked to the primary industrial activity in the municipality of Santa Cruz de Tenerife.

The impact of the COVID-19 pandemic on childhood vaccination rates and the role of sociodemographic factors: A cohort study.

OBJECTIVE: This study examines the impact of the COVID-19 pandemic on both routine and non-routine vaccinations in infants during their initial 18 months of life, concurrently exploring the complex influence of sociodemographic factors. METHODS: A cohort study was conducted, involving 2007 children in two distinct periods: pre-pandemic (January-June 2018) and pandemic (March 2020-May 2021). Participants were classified into two cohorts: 962 children in the 2018 group and 1045 children in the 2020-21 group. Utilizing unconditional logistic regression, the association between vaccination (complete or non-routine) and socioeconomic factors was examined, with adjustments for potential confounding variables such as age, breastfeeding, gestational age, and twins. RESULTS: The study's analysis reveals that in the post-pandemic period, mothers were three times more likely to opt for non-routine vaccines (95% CI 2.25-4.23). However, no significant alterations were observed in routine vaccination rates. Protective factors for complete vaccination included having an employed mother, higher education, and a medium-to-high income. Conversely, a higher income was associated with a reduced likelihood of complete vaccination (OR 0.34, 95% CI 0.20-0.59). CONCLUSION: Contrary to initial expectations, this study concludes that the COVID-19 pandemic did not have a substantial impact on childhood complete vaccination rates. Nevertheless, a noticeable increase in the choice of non-routine vaccination was observed. Sociodemographic factors, such as maternal education, income, and employment status, emerged as key influencers, particularly in the context of deciding on non-routine vaccinations.

Comparative analysis of optical and numerical models for reflectance and color prediction of monolithic dental resin composites with varying thicknesses.

OBJECTIVE: To assess the prediction accuracy of recent optical and numerical models for the spectral reflectance and color of monolithic samples of dental materials with different thicknesses. METHODS: Samples of dental resin composites of Aura Easy Flow (Ae1, Ae3 and Ae4 shades) and Estelite Universal Flow Super Low (A1, A2, A3, A3.5, A4 and A5 shades) with thicknesses between 0.3 and 1.8 mm, as well as Estelite Universal Flow Medium (A2, A3, OA2 and OA3 shades) with thicknesses between 0.4 and 2.0 mm, were used. Spectral reflectance and transmittance factors of all samples were measured using a X-Rite Color i7 spectrophotometer. Four analytical optical models (2 two-flux models and 2 four-flux models) and two numerical models (PCA-based and L*a*b*-based) were implemented to predict spectral reflectance of all samples and then convert them into CIE-L*a*b* color coordinates (D65 illuminant, 2°Observer). The CIEDE2000 total color difference formula (ΔE00) between predicted and measured colors, and the corresponding 50:50% acceptability and perceptibility thresholds (AT00 and PT00) were used for performance assessment. RESULTS: The best performing optical model was the four-flux model RTE-4F-RT, with an average ΔE00 = 0.72 over all samples, 94.87% of the differences below AT00 and 65.38% below PT00. The best performing numerical model was L*a*b*-PCHIP (interpolation mode), with an average ΔE00 = 0.48, and 100% and 79.69% of the differences below AT00 and PT00, respectively. SIGNIFICANCE: Both optical and numerical models offer comparable color prediction accuracy, offering flexibility in model choice. These results help guide decision-making on prediction methods by clarifying their strengths and limitations.

Enterolignans: from natural origins to cardiometabolic significance, including chemistry, dietary sources, bioavailability, and activity.

The enterolignans, enterolactone and enterodiol, the main metabolites produced from plant lignans by the gut microbiota, have enhanced bioavailability and activity compared to their precursors, with beneficial effects on metabolic and cardiovascular health. Although extensively studied, the biosynthesis, cardiometabolic effects, and other therapeutic implications of mammalian lignans are still incompletely understood. The aim of this review is to provide a comprehensive overview of these phytoestrogen metabolites based on up-to-date information reported in studies from a wide range of disciplines. Established and novel synthetic strategies are described, as are the various lignan precursors, their dietary sources, and a proposed metabolic pathway for their conversion to enterolignans. The methodologies used for enterolignan analysis and the available data on pharmacokinetics and bioavailability are summarized and their cardiometabolic bioactivity is explored in detail. The special focus given to research on the health benefits of microbial-derived lignan metabolites underscores the critical role of lignan-rich diets in promoting cardiovascular health.

Evolution of Medical Students' Interest in Orthopaedic Surgery Careers from Matriculation to Graduation.

Introduction: Little is known about risk factors for changes in students' interest in orthopaedics during medical school. We aimed to identify variables associated with diminished (vs. sustained) and emerging (vs. no) plans to become board certified in orthopaedic surgery. Methods: We conducted a retrospective national-cohort study of students who matriculated in US MD-granting medical schools in academic years 1993 to 1994 through 2000 to 2001. The outcome measure was the evolution of students' board-certification plans in orthopaedic surgery from matriculation to graduation using responses on the Association of American Medical Colleges' Matriculating Student Questionnaire and Graduation Questionnaire. Covariates included demographic, attitudinal, experiential, and career intention variables. Results: Of 53,560 graduates with complete data, 2,765 students reported diminished interest in becoming board certified in orthopaedics, 1,345 reported emerging interest, and 1,327 reported sustained interest. In multivariable logistic regression models, students who were female (adjusted odds ratio [aOR] 1.83, 95% confidence interval [CI] 1.43-2.34), Asian (aOR 1.46, 95% CI 1.18-1.82), reported greater importance of social responsibility (aOR 1.16, 95% CI 1.02-1.33) and prestige (aOR 1.20, 95% CI 1.10-1.30) in choosing a medicine career, and planned full-time university faculty careers (aOR 1.58, 95% CI 1.33-1.89) at graduation were independently more likely to have diminished (vs. sustained) interest. Students who participated in research and/or authorship electives (aOR 3.50, 95% CI 3.00-4.07) and who attended private institutions (aOR 1.23, 95% CI 1.10-1.39) were more likely to have emerging (vs. no) interest. Conclusions: Twice as many students lost interest than gained interest in orthopaedics during medical school, and the cohort of students interested in orthopaedics became less diverse over the course of medical school. Several risk factors amenable to change were identified. Interventions that target these risk factors are warranted to increase the diversity of the orthopaedic surgery workforce.

Identification of a pathogenic mutation in ARPP21 in patients with amyotrophic lateral sclerosis.

BACKGROUND AND OBJECTIVE: Between 5% and 10% of amyotrophic lateral sclerosis (ALS) cases have a family history of the disease, 30% of which do not have an identifiable underlying genetic cause after a comprehensive study of the known ALS-related genes. Based on a significantly increased incidence of ALS in a small geographical region from Spain, the aim of this work was to identify novel ALS-related genes in ALS cases with negative genetic testing. METHODS: We detected an increased incidence of both sporadic and, especially, familial ALS cases in a small region from Spain compared with available demographic and epidemiological data. We performed whole genome sequencing in a group of 12 patients with ALS (5 of them familial) from this unique area. We expanded the study to include affected family members and additional cases from a wider surrounding region. RESULTS: We identified a shared missense mutation (c.1586C>T; p.Pro529Leu) in the cyclic AMP regulated phosphoprotein 21 (ARPP21) gene that encodes an RNA-binding protein, in a total of 10 patients with ALS from 7 unrelated families. No mutations were found in other ALS-causing genes. CONCLUSIONS: While previous studies have dismissed a causal role of ARPP21 in ALS, our results strongly support ARPP21 as a novel ALS-causing gene.

Geographic and dietary differences of urinary uranium levels in the Strong Heart Family Study.

BACKGROUND: American Indian (AI) communities are affected by uranium exposure from abandoned mines and naturally contaminated drinking water. Few studies have evaluated geographical differences across AI communities and the role of dietary exposures. OBJECTIVE: We evaluated differences in urinary uranium levels by diet and geographical area among AI participants from the Northern Plains, the Southern Plains, and the Southwest enrolled in the Strong Heart Family Study (SHFS). METHODS: We used food frequency questionnaires to determine dietary sources related to urinary uranium levels for 1,682 SHFS participants in 2001-2003. We calculated adjusted geometric mean ratios (GMRs) of urinary uranium for an interquartile range (IQR) increase in self-reported food group consumption accounting for family clustering and adjusting for sociodemographic variables and other food groups. We determined the percentage of variability in urinary uranium explained by diet. RESULTS: Median (IQR) urinary uranium levels were 0.027 (0.012, 0.057) µg/g creatinine. Urinary uranium levels were higher in Arizona (median 0.039 µg/g) and North Dakota and South Dakota (median 0.038 µg/g) and lower in Oklahoma (median 0.019 µg/g). The adjusted percent increase (95% confidence interval) of urinary uranium levels per IQR increase in reported food intake was 20% (5%, 36%) for organ meat, 11% (1%, 23%) for cereals, and 14% (1%, 29%) for alcoholic drinks. In analyses stratified by study center, the association with organ meat was specific to North Dakota and South Dakota participants. An IQR increase in consumption of fries and chips was inversely associated with urinary uranium levels -11% (-19%, -3%). Overall, we estimated that self-reported dietary exposures explained 1.71% of variability in urine uranium levels. IMPACT: Our paper provides a novel assessment of self-reported food intake and urinary uranium levels in a cohort of American Indian participants. We identify foods (organ meat, cereals, and alcohol) positively associated with urinary uranium levels, find that organ meat consumption is only associated with urine uranium in North Dakota and South Dakota, and estimate that diet explains relatively little variation in total urinary uranium concentrations. Our findings contribute meaningful data toward a more comprehensive estimation of uranium exposure among Native American communities and support the need for high-quality assessments of water and dust uranium exposures in SHFS communities.

Regional Workshop on Optimization of Protection in Pediatric Interventional Radiology in Latin American and Caribbean Countries.

ABSTRACT: The purpose of this article is to describe the activities developed within the framework "Regional Workshop on Optimization of Protection in Pediatric Interventional Radiology in Latin American and Caribbean countries," developed between October 16th and 19th of the year 2023 in the city of San José, Costa Rica. The workshop was carried out as part of a joint work between the Pan American Health Organization (PAHO) and the World Health Organization (WHO), in cooperation with the International Atomic Energy Agency (IAEA). The main objective of the regional workshop was to gather the experiences and future work planning among participants in the Optimization of Protection in Pediatric Interventional Radiology in Latin America and the Caribbean (OPRIPALC) program. It involved professionals from 14 centers across 11 countries in the region, along with 4 experts from PAHO/WHO/IAEA. The work modalities during the workshop consisted of keynote presentations, individual presentations, group work, and general discussions. An online survey was carried out after the workshop, with the objective of knowing the opinion of the event participants and determining the impact and projection of the OPRIPALC program. During the workshop the centers had to present their experiences: the use of the DOLQA dose management system was presented and work was done on the consensus document on good practices. The activities, topics and organization of the workshop were valued positively by the participants. There is unanimity among the centers that the OPRIPALC program has had a positive impact and they wish to continue actively participating in the next biennium.

Role of fibroblast growth factor-23 as an early marker of metabolic bone disease of prematurity.

PURPOSE: Metabolic bone disease of prematurity (MBDP) remains a significant cause of morbidity in extremely premature newborns. In high-risk patients, suspected diagnosis and subsequent treatment modifications, with limitations in terms of sensitivity and specificity, rely on low phosphorus levels and/or high levels of alkaline phosphatase (ALP). We investigated the potential of fibroblast growth factor-23 (FGF23) as an early marker for MBDP when measured at 3-4 weeks of life in at-risk patients. METHODS: A single-center prospective observational non-interventional study including preterm newborns of both sexes, with a gestational age of less than 32 weeks and/or a birth weight of less than 1500 g. In the standard biochemical screening for MBDP performed between 3 and 4 weeks of life within a nutritional profile, the determination of FGF23 was included along with other clinical and metabolic studies. The study was conducted at Marqués de Valdecilla University Hospital in Santander, Spain, from April 2020 to March 2021. Participants provided informed consent. Biochemical analyses were conducted using various platforms, and follow-up evaluations were performed at the discretion of neonatologists. Patients at high risk for MBDP received modifications in treatment accordingly. The sample was descriptively analyzed, presenting measures of central tendency and dispersion for continuous variables, and absolute numbers/percentages for categorical ones. Tests used included t-tests, Mann‒Whitney U tests, chi-square tests, logistic regressions, Pearson correlation, and ROC curve analysis (IBM SPSS Statistics version 19). Significance level: P < 0.05. RESULTS: In the study involving 25 at-risk premature newborns, it was found that 20% (n = 5) were diagnosed with MBDP. Three of these patients (60%) were identified as high-risk based on standard biochemical evaluation at 3-4 weeks of age, while the other two patients (40%) were diagnosed in subsequent weeks. However, in all 5 patients, measurement of FGF23 levels would allow for early identification and optimization of treatment before other markers become altered. Low levels of FGF23 at 3-4 weeks, even with normal phosphorus and ALP levels, indicate the need for modifications in nutritional supplementation. CONCLUSIONS: MBDP remains a significant concern in extremely premature newborns. Current diagnostic methods rely on limited biochemical markers. Early detection of low FGF23 levels enables timely interventions, potentially averting demineralization.

QTL discovery for agronomic and quality traits in diploid potato clones using PotatoMASH amplicon sequencing.

We genotyped a population of 618 diploid potato clones derived from six independent potato-breeding programmes from NW-Europe. The diploids were phenotyped for 23 traits, using standardised protocols and common check varieties, enabling us to derive whole population estimators for most traits. We subsequently performed a Genome-Wide Association Study (GWAS) to identify quantitative trait loci (QTL) for all traits with SNPs and short-read haplotypes derived from read-backed phasing. In this study, we used a marker platform called PotatoMASH (Potato Multi-Allele Scanning Haplotags); a pooled multiplex amplicon sequencing based approach. Through this method, neighbouring SNPs within an amplicon can be combined to generate multi-allelic short-read haplotypes (haplotags) that capture recombination history between the constituent SNPs, and reflect the allelic diversity of a given locus in a different way than single bi-allelic SNPs. We found a total of 37 unique QTL across both marker types. A core of 10 QTL were detected with SNPs as well as with haplotags. Haplotags allowed to detect an additional 14 QTL not found based on the SNP set. Conversely, the bi-allelic SNP set also found 13 QTL not detectable using the haplotag set. We conclude that both marker types should routinely be used in parallel to maximize the QTL detection power. We report 19 novel QTL for nine traits: Skin Smoothness, Sprout Dormancy, Total Tuber Number, Tuber Length, Yield, Chipping Colour, After-cooking Blackening, Cooking Type and Eye depth.

Effectiveness and one-year whiteness stability of different in-office bleaching agents and alternative protocols.

STATEMENT OF PROBLEM: In-office bleaching has been widely researched. However, few studies have evaluated alternative protocols for this procedure. Moreover, information on the long-term stability of in-office whitening is limited. PURPOSE: The purpose of this in vitro study was to evaluate the effectiveness and 1-year stability of in-office bleaching with 35% hydrogen peroxide (35%HP) and 37% carbamide peroxide (37%CP) using traditional and alternative protocols. MATERIAL AND METHODS: Forty human third molars were stained with tea and allocated to groups (n=10). Traditional protocols consisted of 3 applications of 35%HP for 15 minutes and 1 application of 37%CP for 45 minutes. Alternative protocols consisted of 1 application of 35%HP for 45 minutes and 3 applications of 37%CP for 45 minutes. Protocols were applied for 3 weeks. CIELab color coordinates were measured at baseline and weekly during treatment and at 1-week, 6-month, and 1-year follow-ups. Effectiveness and stability of the bleaching treatments were interpreted using 50:50% perceptibility and acceptability thresholds. CIELab, chroma, hue angle, and whiteness index were analyzed using the Wilcoxon signed-rank test (α=.05). RESULTS: All protocols showed improvement in bleaching after the first week (P≤.005). All bleaching procedures presented excellent whitening outcomes. Alternative protocols showed a larger rebound effect after 1 year, indicating less stability. For the whiteness index, no differences between the completion of the treatments and 1-year follow-up was found for the bleaching treatments and protocols (P>.05), except for the 37%CP alternative protocol (P=.005). CONCLUSIONS: All tested protocols presented excellent effectiveness in bleaching. Traditional protocols exhibited a greater whiteness stability, while the alternative protocols showed a greater rebound effect after 1 year.

SEOM-GEICO clinical guideline on epithelial ovarian cancer (2023).

In recent years, the incorporation of new strategies to the therapeutic armamentarium has completely changed the outcomes of epithelial ovarian cancer (EOC). The identification of new predictive and prognostic biomarkers has also enabled the selection of those patients more likely to respond to targeted agents. Nevertheless, EOC is still a highly lethal disease and resistance to many of these new agents is common. The objective of this guideline is to summarize the most relevant strategies to manage EOC, to help the clinician throughout the challenging diagnostic and therapeutic processes and to provide evidence-based recommendations.

Novel Genetic Variants Explaining Severe Adverse Drug Events after Clinical Implementation of DPYD Genotype-Guided Therapy with Fluoropyrimidines: An Observational Study.

Fluoropyrimidines (FPs) are commonly prescribed in many cancer streams. The EMA and FDA-approved drug labels for FPs recommend genotyping the DPYD*2A (rs3918290), *13 (rs55886062), *HapB3 (rs56038477), alleles, and DPYD rs67376798 before treatment starts. We implemented the DPYD genotyping in our daily clinical routine, but we still found patients showing severe adverse drug events (ADEs) to FPs. We studied among these patients the DPYD rs1801265, rs17376848, rs1801159, rs1801160, rs1801158, and rs2297595 as explanatory candidates of the interindividual differences for FP-related toxicities, examining the association with the response to FPs . We also studied the impact of DPYD testing for FP dose tailoring in our clinical practice and characterized the DPYD gene in our population. We found a total acceptance among physicians of therapeutic recommendations translated from the DPYD test, and this dose tailoring does not affect the treatment efficacy. We also found that the DPYD*4 (defined by rs1801158) allele is associated with a higher risk of ADEs (severity grade ≥ 3) in both the univariate (O.R. = 5.66; 95% C.I. = 1.35-23.67; p = 0.014) and multivariate analyses (O.R. = 5.73; 95% C.I. = 1.41-28.77; p = 0.019) among FP-treated patients based on the DPYD genotype. This makes it a candidate variant for implementation in clinical practice.