Comparative Study of the Effectiveness of Vedolizumab Versus Ustekinumab After Anti-TNF Failure in Crohn's Disease (Versus-CD): Data from the ENEIDA Registry.

BACKGROUND: Both vedolizumab and ustekinumab are approved for the management of Crohn's disease [CD]. Data on which one would be the most beneficial option when anti-tumour necrosis factor [anti-TNF] agents fail are limited. AIMS: To compare the durability, effectiveness, and safety of vedolizumab and ustekinumab after anti-TNF failure or intolerance in CD. METHODS: CD patients from the ENEIDA registry who received vedolizumab or ustekinumab after anti-TNF failure or intolerance were included. Durability and effectiveness were evaluated in both the short and the long term. Effectiveness was defined according to the Harvey-Bradshaw index [HBI]. The safety profile was compared between the two treatments. The propensity score was calculated by the inverse probability weighting method to balance confounder factors. RESULTS: A total of 835 patients from 30 centres were included, 207 treated with vedolizumab and 628 with ustekinumab. Dose intensification was performed in 295 patients. Vedolizumab [vs ustekinumab] was associated with a higher risk of treatment discontinuation (hazard ratio [HR] 2.55, 95% confidence interval [CI]: 2.02-3.21), adjusted by corticosteroids at baseline [HR 1.27; 95% CI: 1.00-1.62], moderate-severe activity in HBI [HR 1.79; 95% CI: 1.20-2.48], and high levels of C-reactive protein at baseline [HR 1.06; 95% CI: 1.02-1.10]. The inverse probability weighting method confirmed these results. Clinical response, remission, and corticosteroid-free clinical remission were higher with ustekinumab than with vedolizumab. Both drugs had a low risk of adverse events with no differences between them. CONCLUSION: In CD patients who have failed anti-TNF agents, ustekinumab seems to be superior to vedolizumab in terms of durability and effectiveness in clinical practice. The safety profile is good and similar for both treatments.

Splanchnic Vein Thrombosis in Inflammatory Bowel Disease: An Observational Study from the ENEIDA Registry and Systematic Review.

BACKGROUND: Thromboembolic events are frequent among patients with inflammatory bowel disease (IBD). However, there is little information on the prevalence, features and outcomes of splanchnic vein thrombosis (SVT) in patients with IBD. AIMS: To describe the clinical features and outcomes of SVT in patients with IBD and to perform a systematic review of these data with published cases and series. METHODS: A retrospective observational study from the Spanish nationwide ENEIDA registry was performed. A systematic search of the literature was performed to identify studies with at least one case of SVT in IBD patients. RESULTS: A new cohort of 49 episodes of SVT from the Eneida registry and 318 IBD patients with IBD identified from the literature review (sixty studies: two multicentre, six single-centre and fifty-two case reports or case series) were analysed. There was a mild predominance of Crohn's disease and the most frequent clinical presentation was abdominal pain with or without fever followed by the incidental finding in cross-sectional imaging techniques. The most frequent SVT location was the main portal trunk in two-thirds of the cases, followed by the superior mesenteric vein. Anticoagulation therapy was prescribed in almost 90% of the cases, with a high rate of radiologic resolution of SVT. Thrombophilic conditions other than IBD itself were found in at least one-fifth of patients. CONCLUSIONS: SVT seems to be a rare (or underdiagnosed) complication in IBD patients. SVT is mostly associated with disease activity and evolves suitably when anticoagulation therapy is started.

Socioeconomic disparities in attention deficit hyperactivity disorder (ADHD) in Sweden: An intersectional ecological niches analysis of individual heterogeneity and discriminatory accuracy (IEN-AIHDA).

We aimed (i) to gain a better understanding of the demographic and socioeconomical distribution of ADHD risk in Sweden; and (ii) to contribute to the critical discussion on medicalization, i.e., the tendency to define and treat behavioural and social problems as medical entities. For this purpose, we analysed the risk of suffering from ADHD in the whole Swedish population aged between 5 and 60 years, across 96 different strata defined by combining categories of gender, age, income, and country of birth. The stratified analysis evidenced considerable risk heterogeneity, with prevalence values ranging from 0.03% in high income immigrant women aged 50-59, to 6.18% in middle income immigrant boys aged 10-14. Our study questions the established idea that behavioural difficulties conceptualized as ADHD should be primarily perceived as a neurological abnormality. Rather, our findings suggest that there is a strong sociological component behind how some individuals become impaired and subject to medicalization.

Geographical and sociodemographic differences in statin dispensation after acute myocardial infarction in Sweden: a register-based prospective cohort study applying analysis of individual heterogeneity and discriminatory accuracy (AIHDA) for basic comparisons of healthcare quality.

BACKGROUND: In Sweden, as in many other countries, official monitoring of healthcare quality is mostly focused on geographical disparities in relation to a desirable benchmark. However, current evaluations could be improved by considering: (1) The intersection of other relevant axes of inequity like age, sex, income and migration status; and (2) The existence of individual heterogeneity around averages. Therefore, using an established quality indicator (ie, dispensation of statins after acute myocardial infarction, AMI), we valuate both geographical and sociodemographic inequalities and illustrate how the analysis of individual heterogeneity and discriminatory accuracy (AIHDA) enhances such evaluations. POPULATION AND METHODS: We applied AIHDA and calculated the area under the receiver operating characteristics curve (AUC) of regional and sociodemographic differences in the statin dispensations of 35 044 patients from 21 Swedish regions and 24 sociodemographic strata who were discharged from the hospital with an AMI diagnosis between January 2011 and December 2013. Following the Swedish National Board of Health and Welfare, we used a benchmark value of 90%. RESULTS: Dispensation of stains after AMI in Sweden did not reach the desired target of 90%. Regional differences were absent/very small (AUC=0.537) while sociodemographic differences were small (AUC=0.618). Women, especially those with immigrant background and older than 65 years, have the lowest proportions of statin dispensations after AMI. CONCLUSIONS: As the AUC statistics are small, interventions trying to achieve the benchmark value should be universal. However, special emphasis should nevertheless be directed towards women, especially older women with immigrant backgrounds.

Benefits of Paediatric to Adult Transition Programme in Inflammatory Bowel Disease: The BUTTERFLY Study of GETECCU and SEGHNP.

(1) Background: Transition is a planned movement of paediatric patients to adult healthcare systems, and its implementation is not yet established in all inflammatory bowel disease (IBD) units. The aim of the study was to evaluate the impact of transition on IBD outcomes. (2) Methods: Multicentre, retrospective and observational study of IBD paediatric patients transferred to an adult IBD unit between 2017-2020. Two groups were compared: transition (≥1 joint visit involving the gastroenterologist, the paediatrician, a programme coordinator, the parents and the patient) and no-transition. Outcomes within one year after transfer were analysed. The main variable was poor clinical outcome (IBD flare, hospitalisation, surgery or any change in the treatment because of a flare). Predictive factors of poor clinical outcome were identified with multivariable analysis. (3) Results: A total of 278 patients from 34 Spanish hospitals were included. One hundred eighty-five patients (67%) from twenty-two hospitals (65%) performed a structured transition. Eighty-nine patients had poor clinical outcome at one year after transfer: 27% in the transition and 43% in the no-transition group (p = 0.005). One year after transfer, no-transition patients were more likely to have a flare (36% vs. 22%; p = 0.018) and reported more hospitalisations (10% vs. 3%; p = 0.025). The lack of transition, as well as parameters at transfer, including IBD activity, body mass index < 18.5 and corticosteroid treatment, were associated with poor clinical outcome. One patient in the transition group (0.4%) was lost to follow-up. (4) Conclusion: Transition care programmes improve patients' outcomes after the transfer from paediatric to adult IBD units. Active IBD at transfer impairs outcomes.

Revisiting socio-economic inequalities in sedentary leisure time in Sweden: An intersectional analysis of individual heterogeneity and discriminatory accuracy (AIHDA).

AIMS: Swedish public health reports have repeatedly provided information about socio-economic inequalities in sedentary leisure time, despite that, in the interest of health equity, physical activity should be equally distributed in the population. Such public health reports, however, neither consider the intersection of multiple socio-demographic factors nor the individual heterogeneity around group averages. Drawing on intersectionality theory, this study aimed to revisit previous findings on sedentary leisure time from Swedish public health surveys and demonstrate how the analysis of individual heterogeneity and discriminatory accuracy (AIHDA) can be used for analysing complex health inequalities. METHODS: Using data from Swedish national public health surveys (2004-2015), we applied the AIHDA to define 72 intersectional groups by categories of age, gender, educational achievement, migration status and household composition. We then calculated (a) the absolute and relative risk of sedentary leisure time and (b) the discriminatory accuracy (DA) of the intersectional grouping. RESULTS: The average risk of sedentary leisure time ranged from 5.8% among native-born, highly educated, young women living alone to 41.0% among immigrated young men, living alone, with low education. The risk was higher in strata comprising immigrated people with low education and lower in strata including native-born, highly educated people. However, the DA of the grouping was poor, indicating a substantial overlap of individual risk between groups. CONCLUSIONS: Using the AIHDA and drawing on intersectionality, this study provides an improved mapping of the socio-economic distribution of sedentary leisure time in Sweden, with the poor DA suggesting universal rather than targeted physical activity interventions.

Long-Term Outcomes of Biological Therapy in Crohn's Disease Complicated With Internal Fistulizing Disease: BIOSCOPE Study From GETECCU.

INTRODUCTION: The prevalence of penetrating complications in Crohn's disease (CD) increases progressively over time, but evidence on the medical treatment in this setting is limited. The aim of this study was to evaluate the effectiveness of biologic agents in CD complicated with internal fistulizing disease. METHODS: Adult patients with CD-related fistulae who received at least 1 biologic agent for this condition from the prospectively maintained ENEIDA registry were included. Exclusion criteria involved those receiving biologics for perianal disease, enterocutaneous, rectovaginal, anastomotic, or peristomal fistulae. The primary end point was fistula-related surgery. Predictive factors associated with surgery and fistula closure were evaluated by multivariate logistic regression and survival analyses. RESULTS: A total of 760 patients from 53 hospitals (673 receiving anti-tumor necrosis factors, 69 ustekinumab, and 18 vedolizumab) were included. After a median follow-up of 56 months (interquartile range, 26-102 months), 240 patients required surgery, with surgery rates of 32%, 41%, and 24% among those under anti-tumor necrosis factor, vedolizumab, or ustekinumab, respectively. Fistula closure was observed in 24% of patients. Older patients, ileocolonic disease, entero-urinary fistulae, or an intestinal stricture distal to the origin of the fistula were associated with a higher risk of surgery, whereas nonsmokers and combination therapy with an immunomodulator reduced this risk. DISCUSSION: Biologic therapy is beneficial in approximately three-quarters of patients with fistulizing CD, achieving fistula closure in 24%. However, around one-third still undergo surgery due to refractory disease. Some patient- and lesion-related factors can identify patients who will obtain more benefit from these drugs.

Mapping sociodemographic and geographical differences in human papillomavirus non-vaccination among young girls in Sweden.

AIMS: Human papillomavirus (HPV) vaccination plays a key role in the prevention of cervical cancer. Yet, disparities in HPV vaccination in Sweden have persisted. Previous research on such disparities has typically focused on singular sociodemographic variables and measures of average risk. Using a multi-categorical approach and drawing on intersectionality theory, this study aimed to provide a more precise mapping of HPV non-vaccination among girls in different sociodemographic groups and geographical areas in Sweden during 2013-2020. METHODS: Using nationwide register data, we conducted a multi-categorical analysis of individual heterogeneity and discriminatory accuracy complemented by a multilevel geographical analysis. We mapped HPV non-vaccination prevalence across 54 strata defined by parental income, education and country of birth, and urban versus rural place of residence. We also disentangled municipal and regional influences on HPV non-vaccination. RESULTS: HPV non-vaccination was more common in groups with a low income, a low education and an immigration background, whereas among those with an immigration background, the association between income, education and HPV non-vaccination was more complex. Geographical differences were found between municipalities. However, the discriminatory accuracy of the sociodemographic and geographical groups was weak, and 50% of the non-vaccination cases were observed in eight strata, of which some are among those with low risk. CONCLUSIONS: Our findings underscore the importance of universal yet tailored approaches, including providing adequate information about HPV vaccination in Swedish and other languages, and of health-care professionals displaying sensitivity to patients' and parents' questions or needs.

Correction: Chaparro et al. Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study. J. Clin. Med. 2021, 10, 2885.

The authors wish to make the following corrections to this paper [...].

Physical and social environmental factors related to co-occurrence of unhealthy lifestyle behaviors.

Previous work identifying determinants of co-occurrence of behavioral risk factors have focused on their association with individuals' characteristics with scant attention paid to their relationship to contextual factors. Data came from 21,007 individuals ≥15 years of age who participated in the cross-sectional 2011-2012 Spanish National Health Survey. Two indicators were defined by tobacco consumption, alcohol intake, diet, physical activity, and body mass index. The first indicator, based on dichotomized measures, ranges from 0 to 5. The second one (unhealthy lifestyle index), ranges from 0 to 15, with 0 denoting the healthiest score. Among the determinants, we examined social support, five perceived characteristics of the neighborhood, and the socioeconomic deprivation index of the census tract of residence. Data were analyzed using multilevel linear and logistic regression models adjusted for the main sociodemographic characteristics. Using the dichotomized indicator, the probability of having 3-5 risk factors versus <3 factors was associated with low social support (Odds Ratio [OR] 1.50; 95% Confidence Interval [CI]: 1.25-1.80). Issues surrounding neighborhood cleanliness (OR = 1.18; 95%CI: 1.04-1.33), air pollution (OR = 1.38; 95%CI: 1.16-1.64), and street crime (OR = 1.21; 95%CI: 1.03-1.42) were associated with determinants of co-occurrence. Risk factors co-occurrence increased as deprivation level increased: the OR for the highest deprivation quintile versus the lowest was 1.30 (95%CI: 1.14-1.48). Similar results were observed when using the unhealthy lifestyle index. Poorer physical and social environments are related to greater co-occurrence of risk factors for chronic diseases. Health promotion interventions targeting the prevention of risk factors should consider the contextual characteristics of the neighborhood environment.

Rapidity of clinical response to adalimumab and improvement of quality of life in luminal Crohn's disease: RAPIDA study.

OBJECTIVE: No studies evaluating the rapidity of response to biological therapies are available for Crohn's disease (CD). The aim of this study was to evaluate rapidity of onset of clinical response and impact on quality of life (QoL) of adalimumab therapy in adult anti-TNF-naïve patients with moderately-to-severely active CD. PATIENTS AND METHODS: RAPIDA was an open-label, single-arm, prospective, multicenter clinical trial. Adult patients with moderately-to-severely active luminal CD, anti-TNF-naïve, and unresponsive to conventional therapy were treated with adalimumab. Clinical disease activity, QoL and inflammatory biomarkers were measured at day 4, and weeks 1, 2, 4, and 12 after treatment initiation. RESULTS: Eighty-six patients were included in the intention-to-treat (ITT) analyses. Clinical disease activity was reduced from a median of 9.0 points to 6.0 points at day 4. Clinical response (≥ 3-point reduction in the Harvey-Bradshaw Index, HBI) was achieved by 61.6% (d4) and 75.6% (w1) of patients in the ITT population (median 2.5 days) and with non-responder imputation (NRI), by 55.8% and 53.4%, respectively. The proportion of patients in clinical remission (HBI<5) at weeks 2 and 4 in the ITT population was 54.7% and 62.8%, respectively (median 7.0 days), and 38.4% and 45.3% in the NRI population. All QoL scores significantly improved and inflammatory biomarkers significantly decreased from day 4 onwards (p<0.0001). CONCLUSION: Rapid clinical response and remission, improvement in QoL and fatigue, and a reduction of inflammatory biomarkers were achieved with adalimumab as early as day 4 in adult anti-TNF-naïve patients with moderately-to-severely active CD.

Antidepressant use in Sweden: an intersectional multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA).

INTRODUCTION: Antidepressants are among the most commonly prescribed drugs in Sweden. However, we lack detailed knowledge on the socioeconomic and demographic distribution of antidepressant use in the population. To fill this gap, we performed an intersectional multilevel analysis of individual heterogeneity and discriminatory accuracy. METHODS: Analysing all Swedish residents older than 10 years (n=8,190,990), we measured the absolute risk of antidepressant use across 144 intersectional strata defined by combinations of age, gender, income, country of birth and psychiatric diagnosis. We calculated the strata-specific absolute risk of antidepressant use in a series of multilevel logistic regression models. By means of the variance partitioning coefficient and the area under the receiver operating characteristic curve, we quantified the discriminatory accuracy of the intersectional contexts (i.e. strata) for discerning those who use antidepressants from those who do not. RESULTS: The absolute risk of antidepressant use ranged between 0.93% and 24.78% among those without a psychiatric diagnosis, and between 21.41% and 77.56% among those with a psychiatric diagnosis. Both the variance partitioning coefficient of 41.88% and the area under the receiver operating characteristic curve of 0.81 were considerable. CONCLUSIONS: Besides overt psychiatric diagnoses, our study shows that antidepressant use is mainly conditioned by age, which might express the embodiment of socioeconomic conditions across the individual life course. Our analysis provides a detailed and highly discriminatory mapping of the heterogeneous distribution of antidepressant use in the Swedish population, which may be useful in public health management.

Population heterogeneity in associations between hormonal contraception and antidepressant use in Sweden: a prospective cohort study applying intersectional multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA).

OBJECTIVES: From a reproductive justice framework, we aimed to investigate how a possible association between hormonal contraceptive (HC) and antidepressants use (as a proxy for depression) is distributed across intersectional strata in the population. We aimed to visualise how intersecting power dynamics may operate in combination with HC use to increase or decrease subsequent use of antidepressants. Our main hypothesis was that the previously observed association between HC and antidepressants use would vary between strata, being more pronounced in more oppressed intersectional contexts. For this purpose, we applied an intersectional multilevel analysis of individual heterogeneity and discriminatory accuracy approach. DESIGN: Observational prospective cohort study using record linkage of national Swedish registers. SETTING: The population of Sweden. PARTICIPANTS: All 915 954 women aged 12-30 residing in Sweden 2010, without a recent pregnancy and alive during the individual 1-year follow-up. PRIMARY OUTCOME MEASURE: Use of any antidepressant, meaning being dispensed at least one antidepressant (ATC: N06A) during follow-up. RESULTS: Previously mentally healthy HC users had an OR of 1.79 for use of antidepressants compared with non-users, whereas this number was 1.28 for women with previous mental health issues. The highest antidepressant use were uniformly found in strata with previous mental health issues, with highest usage in women aged 24-30 with no immigrant background, low income and HC use (51.4%). The largest difference in antidepressant use between HC users and non-users was found in teenagers, and in adult women of immigrant background with low income. Of the total individual variance in the latent propensity of using antidepressant 9.01% (healthy) and 8.16% (with previous mental health issues) was found at the intersectional stratum level. CONCLUSIONS: Our study suggests teenagers and women with immigrant background and low income could be more sensitive to mood effects of HC, a heterogeneity important to consider moving forward.

Orangutan information broadcast via consonant-like and vowel-like calls breaches mathematical models of linguistic evolution.

The origin of language is one of the most significant evolutionary milestones of life on Earth, but one of the most persevering scientific unknowns. Two decades ago, game theorists and mathematicians predicted that the first words and grammar emerged as a response to transmission errors and information loss in language's precursor system, however, empirical proof is lacking. Here, we assessed information loss in proto-consonants and proto-vowels in human pre-linguistic ancestors as proxied by orangutan consonant-like and vowel-like calls that compose syllable-like combinations. We played back and re-recorded calls at increasing distances across a structurally complex habitat (i.e. adverse to sound transmission). Consonant-like and vowel-like calls degraded acoustically over distance, but no information loss was detected regarding three distinct classes of information (viz. individual ID, context and population ID). Our results refute prevailing mathematical predictions and herald a turning point in language evolution theory and heuristics. Namely, explaining how the vocal-verbal continuum was crossed in the hominid family will benefit from future mathematical and computational models that, in order to enjoy empirical validity and superior explanatory power, will be informed by great ape behaviour and repertoire.

Clinical features, therapeutic requirements and evolution of patients with Crohn's disease and upper gastrointestinal involvement (CROHNEX study).

BACKGROUND: Crohn's disease (CD) with upper gastrointestinal involvement (UGI) may have a more aggressive and refractory course. However, evidence on this phenotype of patients is scarce. AIMS: To identify the clinical characteristics, therapeutic requirements and complications associated with UGI in CD METHODS: Nationwide study of cases (UGI, UGI plus ileal/ileocolonic involvement) paired with controls (ileal/ileocolonic involvement) from the ENEIDA registry. Cases were matched to 2 controls by year of diagnosis ± 2.5 years. Patients with exclusive/predominant colonic location or complex perianal fistula were excluded. RESULTS: Of 24 738 patients with CD in the ENEIDA registry, we identified 4058 with UGI (16% of the total CD cohort). Finally, 854 cases and 1708 controls were included. Cases were independently associated to extensive involvement (OR 2.7 [2.2-3.3], P < 0.0001), strictures [OR 1.8 (1.5-2.2), P < 0.0001], chronic iron deficiency anaemia [OR 2.2 (1.3-3.2), P < 0.001] and use of second-line biologics [OR 1.7 (1.1-2.6), P = 0.021]. The median stricture-free time was 14 years (95% CI, 12-16) for cases vs 21 years (95% CI, 19-23) for controls (P < 0.0001). Cases with isolated UGI compared to UGI plus ileal/ileocolonic more frequently had localised disease [OR 0.5(0.3-0.8), P = 0.003] and underwent more endoscopic stricture dilations [OR 2.7(1.3-5.4), P = 0.006]. CONCLUSIONS: The largest cohort of patients with CD and UGI provides information on the natural history of this particular phenotype. Increased awareness of the clinical picture and therapeutic requirements of these patients could lead to earlier diagnosis and treatment of upper gastrointestinal lesions, preventing the structural damage frequently seen in these patients at diagnosis and during follow-up.

Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study.

(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD-Crohn's disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)-during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100,000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31-56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery.

Picturing Breast Cancer Brain Metastasis Development to Unravel Molecular Players and Cellular Crosstalk.

With breast cancer (BC) therapy improvements, the appearance of brain metastases has been increasing, representing a life-threatening condition. Brain metastasis formation involves BC cell (BCC) extravasation across the blood-brain barrier (BBB) and brain colonization by unclear mechanisms. We aimed to disclose the actors involved in BC brain metastasis formation, focusing on BCCs' phenotype, growth factor expression, and signaling pathway activation, correlating with BBB alterations and intercellular communication. Hippocampi of female mice inoculated with 4T1 BCCs were examined over time by hematoxylin-eosin, immunohistochemistry and immunofluorescence. Well-established metastases were observed at seven days, increasing thereafter. BCCs entering brain parenchyma presented mesenchymal, migratory, and proliferative features; however, with time, they increasingly expressed epithelial markers, reflecting a mesenchymal-epithelial transition. BCCs also expressed platelet-derived growth factor-B, ß4 integrin, and focal adhesion kinase, suggesting autocrine and/or paracrine regulation with adhesion signaling activation, while balance between Rac1 and RhoA was associated with the motility status. Intercellular communication via gap junctions was clear among BCCs, and between BCCs and endothelial cells. Thrombin accumulation, junctional protein impairment, and vesicular proteins increase reflect BBB alterations related with extravasation. Expression of plasmalemma vesicle-associated protein was increased in BCCs, along with augmented vascularization, whereas pericyte contraction indicated mural cells' activation. Our results provide further understanding of BC brain metastasis formation, disclosing potential therapeutic targets.

Recommendations of the Spanish Working Group on Crohn's disease and Ulcerative Colitis (Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa - GETECCU) on dysplasia screening in inflammatory bowel disease patients. / Recomendaciones del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre cribado de displasia en pacientes con enfermedad inflamatoria intestinal.

Colonic inflammatory bowel diseases have a higher risk of developing colorectal cancer compared to the general population, which is why they require endoscopic screening techniques with specific follow-up intervals based on the different risk factors described on the literature. This position paper analyzes the current scientific evidence for the different endoscopic techniques available today, how their implementation should be carried out in endoscopic units and describes in detail how their implementation should be carried out, in which patients and with what interval, and finally, what should be the response to finding dysplasia, proposing a specific follow-up algorithm.

An intersectional analysis providing more precise information on inequities in self-rated health.

BACKGROUND: Intersectionality theory combined with an analysis of individual heterogeneity and discriminatory accuracy (AIHDA) can facilitate our understanding of health disparities. This enables the application of proportionate universalism for resource allocation in public health. Analyzing self-rated health (SRH) in Sweden, we show how an intersectional perspective allows for a detailed mapping of health inequalities while avoiding simplification and stigmatization based on indiscriminate interpretations of differences between group averages. METHODS: We analyzed participants (n=133,244) in 14 consecutive National Public Health Surveys conducted in Sweden in 2004-2016 and 2018. Applying AIHDA, we investigated the risk of bad SRH across 12 intersectional strata defined by gender, income and migration status, adjusted by age and survey year. We calculated odds ratios (with 95% confidence intervals) to evaluate between-strata differences, using native-born men with high income as the comparison reference. We calculated the area under the receiver operating characteristic curve (AU-ROC) to evaluate the discriminatory accuracy of the intersectional strata for identifying individuals according to their SRH status. RESULTS: The analysis of intersectional strata showed clear average differences in the risk of bad SRH. For instance, the risk was seven times higher for immigrated women with low income (OR 7.00 [95% CI 6.14-7.97]) than for native men with high income. However, the discriminatory accuracy of the intersectional strata was small (AU-ROC=0.67). CONCLUSIONS: The intersectional AIHDA approach provides more precise information on the existence (or the absence) of health inequalities, and can guide public health interventions according to the principle of proportionate universalism. The low discriminatory accuracy of the intersectional strata found in this study warrants universal interventions rather than interventions exclusively focused on strata with a higher average risk of bad SRH.