Prognostic genome and transcriptome signatures in colorectal cancers.

Colorectal cancer is caused by a sequence of somatic genomic alterations affecting driver genes in core cancer pathways1. Here, to understand the functional and prognostic impact of cancer-causing somatic mutations, we analysed the whole genomes and transcriptomes of 1,063 primary colorectal cancers in a population-based cohort with long-term follow-up. From the 96 mutated driver genes, 9 were not previously implicated in colorectal cancer and 24 had not been linked to any cancer. Two distinct patterns of pathway co-mutations were observed, timing analyses identified nine early and three late driver gene mutations, and several signatures of colorectal-cancer-specific mutational processes were identified. Mutations in WNT, EGFR and TGFß pathway genes, the mitochondrial CYB gene and 3 regulatory elements along with 21 copy-number variations and the COSMIC SBS44 signature correlated with survival. Gene expression classification yielded five prognostic subtypes with distinct molecular features, in part explained by underlying genomic alterations. Microsatellite-instable tumours divided into two classes with different levels of hypoxia and infiltration of immune and stromal cells. To our knowledge, this study constitutes the largest integrated genome and transcriptome analysis of colorectal cancer, and interlinks mutations, gene expression and patient outcomes. The identification of prognostic mutations and expression subtypes can guide future efforts to individualize colorectal cancer therapy.

Clinical and genetic factors associated with tumor response to neoadjuvant (chemo)radiotherapy, survival and recurrence risk in rectal cancer.

Rectal cancer poses challenges in preoperative treatment response, with up to 30% achieving a complete response (CR). Personalized treatment relies on accurate identification of responders at diagnosis. This study aimed to unravel CR determinants, overall survival (OS), and time to recurrence (TTR) using clinical and targeted sequencing data. Analyzing 402 patients undergoing preoperative treatment, tumor stage, size, and treatment emerged as robust response predictors. CR rates were higher in smaller, early-stage, and intensively treated tumors. Targeted sequencing analyzed 216 cases, while 120 patients provided hotspot mutation data. KRAS mutation dramatically reduced CR odds by over 50% (odds ratio [OR] = 0.3 in the targeted sequencing and OR = 0.4 hotspot cohorts, respectively). In contrast, SMAD4 and SYNE1 mutations were associated with higher CR rates (OR = 6.0 and 6.8, respectively). Favorable OS was linked to younger age, CR, and low baseline carcinoembryonic antigen levels. Notably, CR and an APC mutation increased TTR, while a BRAF mutation negatively affected TTR. Beyond tumor burden, SMAD4 and SYNE1 mutations significantly influenced CR. KRAS mutations independently correlated with radiotherapy resistance, and BRAF mutations heightened recurrence risk. Intriguingly, non-responding tumors with initially small sizes carried a higher risk of recurrence. The findings, even if limited in addition to the imperfect clinical factors, offer insights into rectal cancer treatment response, guiding personalized therapeutic strategies. By uncovering factors impacting CR, OS, and TTR, this study underscores the importance of tailored approaches for rectal cancer patients. These findings, based on extensive analysis and mutation data, pave the way for personalized interventions, optimizing outcomes in the challenges of rectal cancer preoperative treatment.

Atypical (non-V600E) BRAF mutations in metastatic colorectal cancer in population and real-world cohorts.

BRAF-V600E mutation (mt) is a strong negative prognostic and predictive biomarker in metastatic colorectal cancer (mCRC). Non-V600Emt, designated atypical BRAFmt (aBRAFmt) are rare, and little is known about their frequency, co-mutations and prognostic and predictive role. These were compared between mutational groups of mCRC patients collected from three Nordic population-based or real-world cohorts. Pathology of aBRAFmt was studied. The study included 1449 mCRC patients with 51 (3%) aBRAFmt, 182 (13%) BRAF-V600Emt, 456 (31%) RAS&BRAF wild-type (wt) and 760 (52%) RASmt tumours. aBRAFmt were seen in 2% of real-world and 4% of population-based cohorts. Twenty-six different aBRAFmt were detected, 11 (22%) class 2 (serrated adenocarcinoma in 2/9 tested), 32 (64%) class 3 (serrated in 15/25) and 4 (8%) unclassified. aBRAFmt patients were predominantly male, had more rectal primaries, less peritoneal metastases, deficient mismatch repair in one (2%), and better survival after metastasectomy (89% 5-year overall survival [OS]-rate) compared with BRAF-V600Emt. aBRAFmt and BRAF-V600Emt had poorer performance status and received fewer treatment lines than RAS&BRAFwt and RASmt. OS among aBRAFmt (median 14.4 months) was longer than for BRAF-V600Emt (11.2 months), but shorter than for RAS&BRAFwt (30.5 months) and RASmt (23.4 months). Addition of bevacizumab trended for better OS for the aBRAFmt. Nine patients with aBRAFmt received cetuximab/panitumumab without response. aBRAFmt represents a distinct subgroup differing from other RAS/BRAF groups, with serrated adenocarcinoma in only half. OS for patients with aBRAFmt tumours was slightly better than for BRAF-V600Emt, but worse than for RASmt and RAS&BRAFwt. aBRAFmt should not be a contraindication for metastasectomy.

Psychometric properties of the health literacy instrument in Brazil (HLS-EU-BR47).

BACKGROUND: Health literacy (HL) is a key component of health promotion and sustainability and contributes to well-being. Despite its global relevance, HL is an under-researched topic in South America but is now debuting its exploration in Brazil. To leverage its benefits for South America, the mere translation of validated tools into Portuguese is insufficient. Rather, it is necessary to examine their validity. This study aims to assess the psychometric properties of the European Health Literacy Questionnaire (HLS-EU-BR47) using the Item Response Theory (IRT) in a population-based sample of adults in Brazil. METHODS: A cross-sectional online study was conducted across Brazil and included 1028 participants aged 18 years and above (80% women). Cronbach's alpha, McDonald's omega, factor analysis, graded responses model, Item Characteristic Curve, HL levels based on this, HL standard calculation, IRT, and regular score correlation were computed. RESULTS: The instrument exhibit high reliability (Cronbach's alpha 0.95). Factor analysis yielded one factor. IRT was appropriate for data analysis because it allowed quality evaluation of items and constructed a scale to quantify HL. The 47 items and latent features of respondents in the same unit of measurement are positioned in the construction of the HLS-EU-BR47 instrument. The percentages of individuals at each HL level, calculated using IRT, were found to be comparable to those obtained through the standard computation, e.g., 3.2% of people reported very low HL versus 10.8% inadequate HL, 56.2% reported low HL versus 39.5% problematic HL, 31.1% had moderate HL versus 30.1% sufficient HL, and 9.5% had high HL versus 19.7% with excellent HL. The mean HL scores were comparable between women and men (33.9 vs. 33.7, P = 0.36). CONCLUSION: This study provides new evidence of the validity of a widely used HL instrument for the population of South America (in this case, Brazil). This tool can be utilized by citizens, health professionals, and regional/national policymakers to inform the development of initiatives to assess and improve the HL of individuals, groups, and communities. Further studies are needed to confirm and extend the findings and to explore the influence of local cultures and practices in the vast Brazilian territory on HL.

Contamination and Carcinogenic Risks of Lead in Lip Cosmetics in China.

There are growing concerns about elevated lead (Pb) levels in lip cosmetics, yet in China, the largest lip cosmetic market, recent Pb contamination in lip cosmetics and associated Pb exposure remain unclear. Here, we measured Pb levels of 29 popular lip cosmetics in China and conducted the bioaccessibility-corrected carcinogenic risk assessments and sensitivity analysis regarding Pb exposure for consumers using Monte Carlo simulation. The Pb concentrations of collected samples ranged from undetectable (< 0.05 µg/kg) to 0.21 mg/kg, all of which were well below the Pb concentration limit set for cosmetics in China (10 mg/kg). The 50th percentile incremental lifetime cancer risk (ILCR) of Pb in Chinese cosmetics (1.20E-07) was below the acceptable level (1E-06), indicating that the application of lip cosmetics and subsequent Pb exposure does not pose carcinogenic risks to consumers in most cases. The results of this study provide new insights into understanding the Pb risk in lip cosmetics.

[Fontan associated liver disease]. / Maladie hépatique associée à la chirurgie de Fontan.

Fontan surgery is vital for infants born with a single-ventricle heart. This intervention establishes a new blood flow circuit bypassing the single ventricle, thereby the separating pulmonary and systemic circulation to preserve single ventricular function. However, it carries risks of hepatic complications, collectively termed Fontan-associated liver disease (FALD), characterized by progressive hepatic congestion and fibrosis potentially leading to an equivalent of cirrhosis. Diagnosis and staging of FALD are complex, requiring multidisciplinary management. In advanced FALD, consideration is given to heart transplantation alone or combined heart-liver transplantation, underscoring the importance of an integrated approach to optimize care for these increasingly more common patients.

La chirurgie de Fontan est vitale pour les nouveau-nés naissant avec un cœur univentriculaire. Cette intervention crée un ­nouveau circuit sanguin palliant l'absence de ventricule sous-pulmonaire en connectant les veines caves directement aux ­artères pulmonaires. Elle permet de séparer les circulations pulmonaire et ­systémique et de préserver la fonction du ventricule unique. Cela expose néanmoins les patients à des complications à moyen et long terme, parmi lesquelles l'atteinte hépatique, nommée ­Fontan-Associated Liver Disease (FALD), se caractérisant par une congestion et une fibrose hépatiques progressives pouvant conduire à l'équivalent d'une cirrhose et à ses complications. Son diagnostic ainsi que l'évaluation de sa sévérité ­impliquent différents éléments biologiques, radiologiques et ­histopathologiques ainsi qu' une expertise multidisciplinaire. Lors de FALD avancée, la transplantation cardiaque seule ou combinée cœur-foie est discutée, au cas par cas.

Eosinophilic Esophagitis beyond Eosinophils - an Emerging Phenomenon Overlapping with Eosinophilic Esophagitis: Collegium Internationale Allergologicum (CIA) Update 2023.

Having long been considered the mainstay in eosinophilic esophagitis (EoE) diagnosis and pathogenesis, the role of eosinophils has been questioned and might be less important than previously thought. It is well known now that EoE is a Th2-mediated disease with many more disease features than eosinophilic infiltration. With more knowledge on EoE, less pronounced phenotypes or nuances of the disease have become apparent. In fact, EoE might be only the tip of the iceberg (and the most extreme phenotype) with several variant forms, at least three, lying on a disease spectrum. Although a common (food induced) pathogenesis has yet to be confirmed, gastroenterologists and allergologists should be aware of these new phenomena in order to further characterize these patients. In the following review, we discuss the pathogenesis of EoE, particularly those mechanisms beyond eosinophilic infiltration of the esophageal mucosa, non-eosinophilic inflammatory cell populations, the new disease entity EoE-like disease, variant forms of EoE, and the recently coined term mast cell esophagitis.

Recurring EPHB1 mutations in human cancers alter receptor signalling and compartmentalisation of colorectal cancer cells.

BACKGROUND: Ephrin (EPH) receptors have been implicated in tumorigenesis and metastasis, but the functional understanding of mutations observed in human cancers is limited. We previously demonstrated reduced cell compartmentalisation for somatic EPHB1 mutations found in metastatic colorectal cancer cases. We therefore integrated pan-cancer and pan-EPH mutational data to prioritise recurrent EPHB1 mutations for functional studies to understand their contribution to cancer development and metastasis. METHODS: Here, 79,151 somatic mutations in 9,898 samples of 33 different tumour types were analysed with a bioinformatic pipeline to find 3D-mutated cluster pairs and hotspot mutations in EPH receptors. From these, 15 recurring EPHB1 mutations were stably expressed in colorectal cancer followed by confocal microscopy based in vitro compartmentalisation assays and phospho-proteome analysis. RESULTS: The 3D-protein structure-based bioinformatics analysis resulted in 63% EPHB1 mutants with compartmentalisation phenotypes vs 43% for hotspot mutations. Whereas the ligand-binding domain mutations C61Y, R90C, and R170W, the fibronectin domain mutation R351L, and the kinase domain mutation D762N displayed reduced to strongly compromised cell compartmentalisation, the kinase domain mutations R743W and G821R enhanced this phenotype. While mutants with reduced compartmentalisation also had reduced ligand induced receptor phosphorylation, the enhanced compartmentalisation was not linked to receptor phosphorylation level. Phosphoproteome mapping pinpointed the PI3K pathway and PIK3C2B phosphorylation in cells harbouring mutants with reduced compartmentalisation. CONCLUSIONS: This is the first integrative study of pan-cancer EPH receptor mutations followed by in vitro validation, a robust way to identify cancer-causing mutations, uncovering EPHB1 mutation phenotypes and demonstrating the utility of protein structure-based mutation analysis in characterization of novel cancer genes. Video Abstract.

[Functional dyspepsia : update 2023]. / Dyspepsie fonctionnelle : update 2023.

Functional dyspepsia is defined by epigastric pain/burning, postprandial fullness and/or early satiety that have been present for at least six months before diagnosis, including three consecutive months, without evidence of an organic cause likely to explain these symptoms. The pathogenesis is complex and incompletely understood. The initial assessment includes a thorough history, physical examination, blood work, celiac disease serology and ruling out Helicobacter pylori infection. Most patients will undergo upper gastrointestinal endoscopy and abdominal ultrasound to exclude organic differential diagnoses. The therapy is multi-facetted and includes, among others, proton pump inhibitors, Helicobacter pylori eradication, herbal agents, and neuromodulators.

La dyspepsie fonctionnelle est définie par la présence d'un ou plusieurs des symptômes suivants : douleur/brûlure épigastrique, plénitude postprandiale, satiété précoce qui doivent être présents depuis au moins six mois avant le diagnostic, dont trois mois consécutifs, sans qu'il y ait de preuve d'une cause organique. La physiopathologie est complexe et mal comprise. Le bilan initial comprend une anamnèse approfondie, un examen physique, un bilan sanguin, une sérologie de la maladie cœliaque et écarter une infection à Helicobacter pylori. Une gastroscopie et un ultrason abdominal sont indiqués chez la majorité des patients afin d'exclure les diagnostics différentiels organiques. Le traitement est multiple et comprend les inhibiteurs de la pompe à proton, l'éradication d'Helicobacter pylori, la phytothérapie et les neuromodulateurs.

Prognostic role of tumour-infiltrating lymphocytes and macrophages in relation to MSI, CDX2 and BRAF status: a population-based study of metastatic colorectal cancer patients.

BACKGROUND: Tumour-infiltrating CD3, CD8 lymphocytes and CD68 macrophages are associated with favourable prognosis in localised colorectal cancer, but the effect in metastatic colorectal cancer (mCRC) is not established. METHODS: A Scandinavian population-based cohort of non-resectable mCRC patients was studied. Tissue microarrays (n = 460) were stained with CD3, CD8 and CD68 using fluorescence-based multiplex immunohistochemistry. Associations with clinicopathological variables, overall survival (OS) and progression-free survival were estimated. RESULTS: Two-thirds of microsatellite instable (MSI) and one-fourth of microsatellite stable (MSS) tumours displayed the highest quartile density of CD8. For CD3 high vs low cases, median OS was 20 vs 16 months (HR: 0.76, 95% CI: 0.59, 0.76, p = 0.025) with 3-year OS of 27 vs 13%. For CD68 high vs low cases, median OS was 23 vs 15 months (HR: 0.69, 95% CI: 0.54, 0.88, p = 0.003) with 3-year OS of 28 vs 12%. MSI, BRAF mutation and CDX2 loss were negative prognostic markers independent of tumour immune infiltration. CONCLUSIONS: In mCRC, high lymphocyte infiltration was found in proportions of MSI and MSS tumours-potential subgroups of immunotherapy response. Tumour-infiltrating CD3 lymphocytes and CD68 macrophages were associated with median and long-term survival. MSI was a significant negative prognostic marker despite high immunogenicity.

Embedded Health Risk from Arsenic in Globally Traded Rice.

International food trade is fundamental to global food security but with often negative consequences in the producing country. We propose a method of quantifying flows of inorganic arsenic (iAs) and embedded increased lifetime cancer risks (EHR) at a global scale, where negative impacts are felt on the importing country. Computations were made for 153 countries. Vietnam exports the most iAs embedded in rice (796 kg/year) followed by India (788 kg/year), Thailand (485 kg/year), and the United States (323 kg/year). We show that continental China, Indonesia, and Malaysia have the highest imports of iAs (292, 174, and 123 kg/year, respectively). Bangladesh ranks highest in EHR followed by Vietnam and Cambodia (150, 141, and 111 per 100,000, respectively). Countries that depend exclusively on imported rice are importing a substantial amount of risk, as, e.g., Kiribati and Solomon Islands (57 and 53 per 100,000, respectively). We discuss the potential policy options for reducing population dietary health risks by well-balanced apportioning of rice sources. This study targets policy design solutions based on health gains, rather than on safe levels of the risk factor alone.

Automated Android Malware Detection Using User Feedback.

The widespread usage of mobile devices and their seamless adaptation to each user's needs through useful applications (apps) makes them a prime target for malware developers. Malware is software built to harm the user, e.g., to access sensitive user data, such as banking details, or to hold data hostage and block user access. These apps are distributed in marketplaces that host millions and therefore have their forms of automated malware detection in place to deter malware developers and keep their app store (and reputation) trustworthy. Nevertheless, a non-negligible number of apps can bypass these detectors and remain available in the marketplace for any user to download and install on their device. Current malware detection strategies rely on using static or dynamic app extracted features (or a combination of both) to scale the detection and cover the growing number of apps submitted to the marketplace. In this paper, the main focus is on the apps that bypass the malware detectors and stay in the marketplace long enough to receive user feedback. This paper uses real-world data provided by an app store. The quantitative ratings and potential alert flags assigned to the apps by the users were used as features to train machine learning classifiers that successfully classify malware that evaded previous detection attempts. These results present reasonable accuracy and thus work to help to maintain a user-safe environment.

[Differential diagnosis and investigation of chronic diarrhea]. / Diagnostic différentiel et investigation de la diarrhée chronique.

Chronic diarrhea is defined by a decrease in stool consistency and a bowel frequency of more than 3 times per day, lasting for at least 4 weeks. Multiple underlying causes may be responsible for chronic diarrhea. There are four main pathomechanisms for chronic diarrhea: osmotic diarrhea, secretory diarrhea, infectious diarrhea and bowel dysmotility. Overlaps between these mechanisms may exist. A stool collection over a 72-hour period frequently allows to classify diarrhea into one of these four entities. Such classification finally helps for the identification of underlying cause(s), thereby allowing rational diagnostic measures. It also limits the costs of diagnostic workup. This article aims to present the main causes of chronic diarrhea, the diagnostic steps to perform and to provide a guideline for clinicians in daily practice.

La diarrhée chronique est définie par une diminution de la consistance des selles (défaites à liquides) et par une émission de selles supérieure à 3 ×/jour pendant plus de 4 semaines. Les raisons peuvent être multiples. Quatre pathomécanismes peuvent être à l'origine de la diarrhée chronique : osmotique, sécrétoire, inflammatoire et motrice. Des chevauchements entre ces mécanismes peuvent exister. La récolte de selles pendant 72 heures permet, dans la majorité des cas, de clarifier la physiopathologie des diarrhées et donc d'identifier la cause sous-­jacente permettant d'effectuer des mesures diagnostiques rationnelles et de limiter les coûts. Cet article a pour objectif de présenter les principales causes de diarrhée chronique, d'énumérer les étapes diagnostiques à réaliser et de donner une ligne directrice aux cliniciens dans la pratique quotidienne.

[Metabolism and therapeutic monitoring of azathioprine in gastroenterology and hepatology]. / Métabolisme et suivi thérapeutique de l'azathioprine en gastroentérologie et hépatologie.

Azathioprine keeps an important place in the treatment of inflammatory bowel disease and autoimmune hepatitis. This molecule has a narrow therapeutic margin, associated with a risk of toxicity, particularly hematological and hepatic. Its complex metabolism is subject to genetic polymorphisms that are reflected in the inter-individual variability observed in the response to treatment and its tolerance profile. Hence, its use requires a good knowledge of this molecule. Treatment is initiated after a preliminary workup, followed by a progressive titration of the dosage while closely monitoring possible toxicities. Monitoring of blood levels of metabolites (including active ones) helps guide personalized dose adjustment.

L'azathioprine garde actuellement une place importante dans le traitement des maladies inflammatoires chroniques de l'intestin et de l'hépatite autoimmune. Il s'agit d'une molécule à marge thérapeutique étroite, associée à un risque de toxicité, notamment hématologique et hépatique. Son métabolisme complexe est influencé par des polymorphismes génétiques qui sont reflétés dans la variabilité interindividuelle observée dans la réponse au traitement et le profil de tolérance. Son utilisation nécessite donc une bonne connaissance de cette molécule. L'instauration du traitement se fait après un bilan préalable, puis une titration progressive des posologies, tout en surveillant étroitement les éventuelles toxicités. Le monitoring des concentrations sanguines des métabolites (notamment actifs) permet de guider l'adaptation personnalisée des posologies.

The relationship of health literacy, wellbeing and religious beliefs in neglected and unequal contexts-Results of a survey study in central Afghanistan.

ISSUE ADDRESSED: While multiple studies worldwide reveal the strong impact of various determinants on health literacy, empirical data on the link between health literacy and other important dimensions of health equity (such as quality of life, beliefs and health literacy in crisis-affected religious countries such as Afghanistan) is scarce. To inform and develop promising health promotion for people in need, we analysed the relationship between health literacy, quality of life and spiritual and religious beliefs. METHODS: In this first study on health literacy in Afghanistan, we interviewed 522 men and 324 women in the Ghazni province. Besides the HLS-EU-16, we used Quality of Life (WHO-QoL-BREF) and the WHO-SRPB-BREF questionnaires in Dari and Pashto. We performed descriptive, uni- and multivariate analyses. RESULTS: The levels of HL, QoL and SRPB_coping are comparatively low among Afghan men from the Ghazni province, but higher among women on all scales. HL and QoL are positively associated with education and negatively with age (in the female subsample). HL and QoL show a moderate correlation among women but not among men. We found mixed results for the relationship between SRPB and HL or QoL. CONCLUSIONS: The study highlights that health literacy is not a singular factor but related to wellbeing. SO WHAT?: Health education might be promising while combining health literacy to the idea of quality of life of everyone, even those living in poor and illiterate environments.

[A practical guide to chronic inflammatory bowel disease]. / Guide pratique de la prise en charge des patients avec maladies inflammatoires chroniques de l'intestin pour les médecins généralistes.

Inflammatory bowel diseases (IBD) comprise Crohn's disease (CD) and ulcerative colitis (UC). IBD develops in patients with genetic susceptibility due to an aberrant response of the intestinal immune system toward gut microbiota. The prevalence of IBD is on the rise in Switzerland, with currently 1/250 persons affected, which corresponds to approximately 35,000 patients. Given the complexity of IBD, patients should be managed by a multidisciplinary team. This article focuses on IBD diagnosis and long-term follow-up.

Les maladies inflammatoires chroniques de l'intestin (MICI) incluent la maladie de Crohn et la rectocolite ulcérohémorragique. Il s'agit de maladies du tube digestif qui se développent suite à une réaction inadaptée du système immunitaire intestinal contre le microbiote chez des patients montrant typiquement des prédispositions génétiques. La prévalence des MICI en Suisse est en augmentation et nous comptons actuellement 1 personne sur 250 (environ 35 000 personnes) affectées par une MICI. La complexité des MICI nécessite une prise en charge multidisciplinaire. Cet article se focalise sur le diagnostic des MICI et le suivi à long terme.

Molecular characterization of a large unselected cohort of metastatic colorectal cancers in relation to primary tumor location, rare metastatic sites and prognosis.

Background: We have reported that BRAF V600E mutations and microsatellite instability-high (MSI-H) are more prevalent in a population-based cohort of metastatic colorectal cancer (mCRC) patients than has been reported from clinical trials or hospital-based patient groups. The aim was to explore if other mutations in mCRC differ in prevalence between these cohorts in relation to mismatch repair status and primary tumor location and if presence of bone or brain metastases is associated with any mutations.Material and methods: A population-based cohort of 798 mCRC patients from three regions in Scandinavia was used. Forty-four cancer related genes were investigated in a custom designed Ampliseq hotspot panel. Differences in survival were analyzed using the Kaplan-Meier estimator and the Cox regression analysis.Results: Determination of mutations was possible in 449/501 patients for 40/44 genes. Besides BRAF V600E, seen in 19% of the tumors, none of the other mutations appeared more prevalent than in trial cohorts. BRAF V600E and MSI-H, seen in 8%, were associated with poor prognosis as was right-sided primary tumor location (39%) when compared to left-sided and rectum together; however, in a multivariable regression, only the BRAF mutation retained its statistical significance. No other mutations were associated with poor prognosis. ERBB2 alterations were more common if bone metastases were present at diagnosis (17% vs. 4%, p = .011). No association was found for brain metastases. Fifty-two percent had an alteration that is treatable with an FDA-approved targeted therapy, chiefly by EGFR-inhibitor for RAS wild-type and a check-point inhibitor for MSI-H tumors.Conclusions: Right-sided tumor location, BRAF V600E mutations, but no other investigated mutation, and MSI-H are more commonly seen in an unselected cohort than is reported from clinical patient cohorts, likely because they indicate poor prognosis. Half of the patients have a tumor that is treatable with an already FDA-approved targeted drug for mCRC.

Health-related Sustainable Development Goals: countdown on alcohol use, smoking prevalence, child overweight and suicide mortality.

The Sustainable Development Goals (SDGs) are a set of goals that aspire to 'leave no one behind', adopted by all members of the United Nations and to be achieved by 2030. Now, four years after the SDGs entered into force, we examine the progress towards the health-related SDGs in the European region. In this region, least progress is made towards the targets set for alcohol consumption, smoking prevalence, child overweight, and suicide mortality. For each of these challenges we take stock of current policies, continuing challenges, and ways forward. Written from the perspective of European Public Health Association (EUPHA) we emphasize the potential contribution of civil society organizations in attaining the health-related SDGs.

Generic health literacy measurement instruments for children and adolescents: a systematic review of the literature.

BACKGROUND: Health literacy is an important health promotion concern and recently children and adolescents have been the focus of increased academic attention. To assess the health literacy of this population, researchers have been focussing on developing instruments to measure their health literacy. Compared to the wider availability of instruments for adults, only a few tools are known for younger age groups. The objective of this study is to systematically review the field of generic child and adolescent health literacy measurement instruments that are currently available. METHOD: A systematic literature search was undertaken in five databases (PubMed, CINAHL, PsycNET, ERIC, and FIS) on articles published between January 1990 and July 2015, addressing children and adolescents ≤18 years old. Eligible articles were analysed, data was extracted, and synthesised according to review objectives. RESULTS: Fifteen generic health literacy measurement instruments for children and adolescents were identified. All, except two, are self-administered instruments. Seven are objective measures (performance-based tests), seven are subjective measures (self-reporting), and one uses a mixed-method measurement. Most instruments applied a broad and multidimensional understanding of health literacy. The instruments were developed in eight different countries, with most tools originating in the United States (n = 6). Among the instruments, 31 different components related to health literacy were identified. Accordingly, the studies exhibit a variety of implicit or explicit conceptual and operational definitions, and most instruments have been used in schools and other educational contexts. While the youngest age group studied was 7-year-old children within a parent-child study, there is only one instrument specifically designed for primary school children and none for early years. CONCLUSIONS: Despite the reported paucity of health literacy research involving children and adolescents, an unexpected number of health literacy measurement studies in children's populations was found. Most instruments tend to measure their own specific understanding of health literacy and not all provide sufficient conceptual information. To advance health literacy instruments, a much more standardised approach is necessary including improved reporting on the development and validation processes. Further research is required to improve health literacy instruments for children and adolescents and to provide knowledge to inform effective interventions.

Health literacy in childhood and youth: a systematic review of definitions and models.

BACKGROUND: Children and young people constitute a core target group for health literacy research and practice: during childhood and youth, fundamental cognitive, physical and emotional development processes take place and health-related behaviours and skills develop. However, there is limited knowledge and academic consensus regarding the abilities and knowledge a child or young person should possess for making sound health decisions. The research presented in this review addresses this gap by providing an overview and synthesis of current understandings of health literacy in childhood and youth. Furthermore, the authors aim to understand to what extent available models capture the unique needs and characteristics of children and young people. METHOD: Six databases were systematically searched with relevant search terms in English and German. Of the n = 1492 publications identified, N = 1021 entered the abstract screening and N = 340 full-texts were screened for eligibility. A total of 30 articles, which defined or conceptualized generic health literacy for a target population of 18 years or younger, were selected for a four-step inductive content analysis. RESULTS: The systematic review of the literature identified 12 definitions and 21 models that have been specifically developed for children and young people. In the literature, health literacy in children and young people is described as comprising variable sets of key dimensions, each appearing as a cluster of related abilities, skills, commitments, and knowledge that enable a person to approach health information competently and effectively and to derive at health-promoting decisions and actions. DISCUSSION: Identified definitions and models are very heterogeneous, depicting health literacy as multidimensional, complex construct. Moreover, health literacy is conceptualized as an action competence, with a strong focus on personal attributes, while also recognising its interrelatedness with social and contextual determinants. Life phase specificities are mainly considered from a cognitive and developmental perspective, leaving children's and young people's specific needs, vulnerabilities, and social structures poorly incorporated within most models. While a critical number of definitions and models were identified for youth or secondary school students, similar findings are lacking for children under the age of ten or within a primary school context.