A practical approach to implementing incremental haemodialysis.

The majority of end-stage kidney disease patients are treated with haemodialysis (HD). Starting HD can pose physical, social, and psychological challenges to patients, and mortality rates within the first 6 months are disproportionately high, with intensive HD regimens implicated as a potential factor. Starting HD with an incremental approach, taking residual kidney function (RKF) into account, potentially allows for a gentle start with reduced dialysis intensity. Dialysis intensity (session time or frequency) can then be proportionally increased as RKF reduces. This approach to starting HD has been reported in observational studies to result in better patient self-reported health quality of life and reduced costs, and now several definitive randomised controlled trials are underway comparing an incremental approach to the conventional thrice weekly paradigm. Physician concerns over the risk of inadequate dialysis, with consequent increased emergency admissions, and practical challenges of how to estimate RKF and implement incremental dialysis have impeded widespread adoption. Addressing these challenges is paramount to increasing the uptake of incremental HD. Careful patient selection lies at the heart of a successful incremental HD programme. Generally, patients with a residual urea clearance of > 3 ml/min/1.73 m2 can be considered suitable for starting with incremental HD provided they comply with fluid intake, salt and other dietary recommendations. Calculating RKF from regular interdialytic urine collections and appropriately adjusting sessional HD clearance targets are practical and conceptual challenges. In this report we aim to disentangle these complexities and provide a step-by-step guide for patient selection and adjusting dialysis sessional targets.

Phase II trial of weekly erlotinib dosing to reduce duodenal polyp burden associated with familial adenomatous polyposis.

IMPORTANCE: Patients with familial adenomatous polyposis (FAP) are at markedly increased risk for duodenal adenomas and cancer. Combination sulindac and erlotinib was previously shown to reduce duodenal polyp burden but was associated with a relatively high adverse event (AE) rate. OBJECTIVE: To evaluate if a once weekly dosing schedule for erlotinib intervention improves the AE profile, while still providing efficacy with respect to reduced polyp burden, in participants with FAP. DESIGN, SETTING AND PARTICIPANTS: Single-arm trial, enrolling 46 participants with FAP, conducted from October 2017 to September 2019 in eight academic cancer centres. EXPOSURES: Participants self-administered 350 mg of erlotinib by mouth, one time per week for 6 months. MAIN OUTCOMES AND MEASURES: Duodenal polyp burden (sum of polyp diameters) was assessed in the proximal duodenum by esophagogastroduodenoscopy performed at baseline and 6 months, with mean per cent change defined as the primary efficacy outcome of interest. Rate of grade 2-3 AEs was evaluated as a co-primary outcome. Secondary outcomes included changes in total duodenal polyp count, along with changes in lower gastrointestinal (GI) polyp burden and count (for participants examined by optional lower endoscopy). RESULTS: Forty-six participants (mean age, 44.1 years (range, 18-68); women, 22 (48%)) were enrolled; 42 participants completed 6 months of intervention and were included in the per-protocol analysis. Duodenal polyp burden was significantly reduced after 6 months of weekly erlotinib intervention, with a mean per cent change of -29.6% (95% CI, -39.6% to -19.7%; p<0.0001). Similar results were observed in subgroup analyses defined by participants with advanced duodenal polyposis (Spigelman 3) at baseline (mean, -27%; 95% CI, -38.7% to -15.2%; p<0.0001). Post-intervention Spigelman stage was downstaged in 12% of the participants. Lower GI polyp number was also decreased after 6 months of intervention (median, -30.8%; IQR, -47.4% to 0.0%; p=0.0256). Grade 2 or 3 AEs were reported in 71.7% of subjects, with only two experiencing grade 3 toxicity at least possibly related to intervention. CONCLUSION: In this single-arm, multi-centre trial of participants with FAP, erlotinib one time per week resulted in markedly lower duodenal polyp burden, and modestly reduced lower GI polyp burden, after 6 months of intervention. While AEs were still reported by nearly three-quarters of all participants, these events were generally lower grade and well-tolerated. These findings support further investigation of erlotinib as an effective, acceptable cancer preventive agent for FAP-associated GI polyposis. TRIAL REGISTRATION NUMBER: NCT02961374.

Impulsividad en el trastorno por déficit de atención e hiperactividad en niños después de una intervención de 8 semanas con dieta mediterránea y/o ácidos grasos omega-3: ensayo clínico aleatorizado / Impulsiveness in children with attention-deficit/hyperactivity disorder after an 8-week intervention with the Mediterranean diet and/or omega-3 fatty acids: A randomised clinical trial

Introducción: La Escala de Impulsividad de Barratt (BIS) es un instrumento de autoinforme diseñado para evaluar la construcción de personalidad y comportamiento de la impulsividad. La impulsividad se ha asociado con varios trastornos psiquiátricos, como el trastorno por déficit de atención e hiperactividad (TDAH). Este estudio evalúa el progreso de la conducta de impulsividad en niños con TDAH después de una intervención dietética de 8 semanas con dieta mediterránea y/o suplemento de ácidos grasos omega-3, mediante el uso de la BIS-11 adaptada para niños (BIS-11c). Métodos: Este estudio transversal incluyó a 60 niños españoles con TDAH de la provincia de Madrid, España. Los participantes se dividieron en 4 grupos, un grupo de control (G1) y 3 grupos de intervención (dieta mediterránea [G2], suplemento de omega-3 [G3] y dieta mediterránea + suplemento de omega-3 [G4]). Se diseñó una dieta mediterránea personalizada para los grupos 2 y 4. Se administró BIS-11c para determinar los niveles de impulsividad y se usó el KIDMED para evaluar la adherencia a la dieta mediterránea. Resultados: El grupo suplemento mostró una caída bastante significativa (p = 0,049) en la puntuación total de Barratt después del seguimiento. La puntuación cognitiva total disminuyó ligeramente en los grupos de dieta y suplemento. Solo el grupo control tuvo una disminución notable con respecto a la puntuación total de la impulsividad motora. Las puntuaciones totales de «falta de planificación» fueron menores en todos los grupos tras la intervención. Las asociaciones entre las puntuaciones iniciales y finales del BIS-11c y los tratamientos presentaron una correlación positiva (r > 0,9). [...](AU)

Introduction: The Barratt Impulsiveness Scale (BIS) is a self-administered instrument designed to assess the personality/behavioural construct of impulsiveness. Impulsiveness has been associated with several psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). This study assesses the progression of impulsive behaviour in children with ADHD after an 8-week dietary intervention with the Mediterranean diet and/or omega-3 fatty acid supplementation, by using a version of the 11-item BIS adapted for children (BIS-11c). Methods: This cross-sectional study includes 60 children with ADHD from the region of Madrid, Spain. Participants were divided into 4 groups, with one control group (G1) and 3 intervention groups (Mediterranean diet [G2]; omega-3 supplementation [G3]; and Mediterranean diet plus omega-3 supplementation [G4]). A personalised Mediterranean diet was designed for members of groups 2 and 4. The BIS-11c was administered to determine the level of impulsiveness, and the KIDMED test was used to assess adherence to the Mediterranean diet. Results: The supplementation group showed a fairly significant decrease in the total BIS-11c (P = .049). Total cognitive score slightly decreased in the diet and supplementation groups. Only the control group showed a considerable decrease in the total motor score. Total nonplanning scores were lower in all groups after the intervention. Baseline and final BIS-11c scores were positively correlated with treatments (r > 0.9). Conclusion: An intake of 550 mg EPA fatty acid and 225 mg DHA fatty acid per day for 8 weeks is associated with less marked impulsive behaviour in children with ADHD. A Mediterranean diet may improve BIS scores, although our results are not conclusive in this population. (AU)

Impulsiveness in children with attention-deficit/hyperactivity disorder after an 8-week intervention with the Mediterranean diet and/or omega-3 fatty acids: a randomised clinical trial.

INTRODUCTION: The Barratt Impulsiveness Scale (BIS) is a self-administered instrument designed to assess the personality/behavioural construct of impulsiveness. Impulsiveness has been associated with several psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). This study assesses the progression of impulsive behaviour in children with ADHD after an 8-week dietary intervention with the Mediterranean diet and/or omega-3 fatty acid supplementation, by using a version of the 11-item BIS adapted for children (BIS-11c). METHODS: This cross-sectional study includes 60 children with ADHD from the region of Madrid, Spain. Participants were divided into 4 groups, with one control group and 3 intervention groups (Mediterranean diet; omega-3 supplementation; and Mediterranean diet plus omega-3 supplementation). A personalised Mediterranean diet was designed for members of groups 2 and 4. The BIS-11c was administered to determine the level of impulsiveness, and the KIDMED test was used to assess adherence to the Mediterranean diet. RESULTS: The supplementation group showed a fairly significant decrease in the total BIS-11c (P = .049). Total cognitive score slightly decreased in the diet and supplementation groups. Only the control group showed a considerable decrease in the total motor score. Total nonplanning scores were lower in all groups after the intervention. Baseline and final BIS-11c scores were positively correlated with treatments (r > 0.9). CONCLUSION: An intake of 550 mg EPA fatty acid and 225 mg DHA fatty acid per day for 8 weeks is associated with less marked impulsive behaviour in children with ADHD. A Mediterranean diet may improve BIS scores, although our results are not conclusive in this population.

Características clínicas, manejo y resultados de los pacientes con endoftalmitis estéril asociados con la inyección intravítrea de factores de crecimiento endotelial antivascular / Clinical features, management and outcomes of patients with sterile endophthalmitis associated with intravitreal injection of antivascular endothelial growth factor

OBJETIVO: Analizar las características clínicas, el manejo y los resultados de los pacientes con endoftalmitis estéril asociada con el factor de crecimiento endotelial antivascular intravítreo. MÉTODOS: Serie de casos de observación retrospectiva de pacientes con endoftalmitis estéril después de inyecciones intravítreas anti-VEGF. Se han revisado los datos clínicos de pacientes tratados con anti-VEGF intravítreos durante un año. Se analizan los que han presentado un episodio de endoftalmitis estéril y se estudia su causalidad y manejo. RESULTADOS: Siete pacientes tuvieron un inicio de endoftalmitis estéril en los 4días posteriores a la inyección intravítrea (aflibercept n = 5 y ranibizumab n = 2). Estos pacientes tienen alguna condición neovascular activa: degeneración macular relacionada con la edad (n = 4), neovascularización coroidea miope (n = 1) o edema macular: edema macular diabético (n = 1), oclusión de la vena retiniana ramificada (n = 1). Los signos y síntomas compartidos incluyeron pérdida de visión indolora, células en cámara anterior o vítrea y falta de hipopión. En todos los pacientes, la agudeza visual volvió a estar dentro de una línea de agudeza basal. CONCLUSIÓN: Diferenciar casos de endoftalmitis estéril de infecciosa puede ser un desafío. Es crucial diferenciar ambas entidades, ya que un buen diagnóstico determina el pronóstico visual. Debemos ser conscientes de una inflamación mínima después de repetidas inyecciones intravítreas para establecer el tratamiento adecuado

PURPOSE: Analyze clinical features, management and outcomes of patients with sterile endophthalmitis associated with intravitreal antivascular endothelial growth factor. METHODS: Observational retrospective case series of patients with sterile endophthalmitis following anti-VEGF intravitreal injections. Clinical data of patients treated with intravitreal anti-VEGFs during one year have been revised. Those who have presented an episode of sterile endophthalmitis are analyzed and their causality and management are studied. RESULTS: Seven patients have had a sterile endophthalmitis onset within 4days after intravitreal injection (aflibercept n = 5 and ranibizumab n = 2). These patients have some active neovascular condition: age related macular degeneration (n = 4), myopic choroidal neovascularization (n = 1) or macular edema: diabetic macular edema (n = 1), branch retinal vein occlusion (n = 1). Shared signs and symptoms included painless vision loss, anterior chamber and vitreous cell and lack of hypopyon. In all patients, visual acuity returned to within one line of baseline acuity. CONCLUSIÓN: Differentiating cases of sterile from infectious endophthalmitis may be challenging. It is crucial to differentiate both entities as a good diagnosis determines the visual prognosis. We should be aware of minimal inflammation after repeated intravitreal injections in order to establish the adequate treatment

Clinical features, management and outcomes of patients with sterile endophthalmitis associated with intravitreal injection of antivascular endothelial growth factor. / Características clínicas, manejo y resultados de los pacientes con endoftalmitis estéril asociados con la inyección intravítrea de factores de crecimiento endotelial antivascular.

PURPOSE: Analyze clinical features, management and outcomes of patients with sterile endophthalmitis associated with intravitreal antivascular endothelial growth factor. METHODS: Observational retrospective case series of patients with sterile endophthalmitis following anti-VEGF intravitreal injections. Clinical data of patients treated with intravitreal anti-VEGFs during one year have been revised. Those who have presented an episode of sterile endophthalmitis are analyzed and their causality and management are studied. RESULTS: Seven patients have had a sterile endophthalmitis onset within 4days after intravitreal injection (aflibercept n=5 and ranibizumab n=2). These patients have some active neovascular condition: age related macular degeneration (n=4), myopic choroidal neovascularization (n=1) or macular edema: diabetic macular edema (n=1), branch retinal vein occlusion (n=1). Shared signs and symptoms included painless vision loss, anterior chamber and vitreous cell and lack of hypopyon. In all patients, visual acuity returned to within one line of baseline acuity. CONCLUSION: Differentiating cases of sterile from infectious endophthalmitis may be challenging. It is crucial to differentiate both entities as a good diagnosis determines the visual prognosis. We should be aware of minimal inflammation after repeated intravitreal injections in order to establish the adequate treatment.

Large-scale analysis of acquired chromosomal alterations in non-tumor samples from patients with cancer.

Mosaicism, the presence of subpopulations of cells bearing somatic mutations, is associated with disease and aging and has been detected in diverse tissues, including apparently normal cells adjacent to tumors. To analyze mosaicism on a large scale, we surveyed haplotype-specific somatic copy number alterations (sCNAs) in 1,708 normal-appearing adjacent-to-tumor (NAT) tissue samples from 27 cancer sites and in 7,149 blood samples from The Cancer Genome Atlas. We find substantial variation across tissues in the rate, burden and types of sCNAs, including those spanning entire chromosome arms. We document matching sCNAs in the NAT tissue and the adjacent tumor, suggesting a shared clonal origin, as well as instances in which both NAT tissue and tumor tissue harbor a gain of the same oncogene arising in parallel from distinct parental haplotypes. These results shed light on pan-tissue mutations characteristic of field cancerization, the presence of oncogenic processes adjacent to cancer cells.

Impulsiveness in children with attention-deficit/hyperactivity disorder after an 8-week intervention with the Mediterranean diet and/or omega-3 fatty acids: A randomised clinical trial. / Impulsividad en el trastorno por déficit de atención e hiperactividad en niños después de una intervención de 8 semanas con dieta mediterránea y/o ácidos grasos omega-3: ensayo clínico aleatorizado.

INTRODUCTION: The Barratt Impulsiveness Scale (BIS) is a self-administered instrument designed to assess the personality/behavioural construct of impulsiveness. Impulsiveness has been associated with several psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD). This study assesses the progression of impulsive behaviour in children with ADHD after an 8-week dietary intervention with the Mediterranean diet and/or omega-3 fatty acid supplementation, by using a version of the 11-item BIS adapted for children (BIS-11c). METHODS: This cross-sectional study includes 60 children with ADHD from the region of Madrid, Spain. Participants were divided into 4 groups, with one control group (G1) and 3 intervention groups (Mediterranean diet [G2]; omega-3 supplementation [G3]; and Mediterranean diet plus omega-3 supplementation [G4]). A personalised Mediterranean diet was designed for members of groups 2 and 4. The BIS-11c was administered to determine the level of impulsiveness, and the KIDMED test was used to assess adherence to the Mediterranean diet. RESULTS: The supplementation group showed a fairly significant decrease in the total BIS-11c (P=.049). Total cognitive score slightly decreased in the diet and supplementation groups. Only the control group showed a considerable decrease in the total motor score. Total nonplanning scores were lower in all groups after the intervention. Baseline and final BIS-11c scores were positively correlated with treatments (r>0.9). CONCLUSION: An intake of 550mg EPA fatty acid and 225mg DHA fatty acid per day for 8 weeks is associated with less marked impulsive behaviour in children with ADHD. A Mediterranean diet may improve BIS scores, although our results are not conclusive in this population.

Anti-EGFR-resistant clones decay exponentially after progression: implications for anti-EGFR re-challenge.

BACKGROUND: Colorectal cancer (CRC) has been shown to acquire RAS and EGFR ectodomain mutations as mechanisms of resistance to epidermal growth factor receptor (EGFR) inhibition (anti-EGFR). After anti-EGFR withdrawal, RAS and EGFR mutant clones lack a growth advantage relative to other clones and decay; however, the kinetics of decay remain unclear. We sought to determine the kinetics of acquired RAS/EGFR mutations after discontinuation of anti-EGFR therapy. PATIENTS AND METHODS: We present the post-progression circulating tumor DNA (ctDNA) profiles of 135 patients with RAS/BRAF wild-type metastatic CRC treated with anti-EGFR who acquired RAS and/or EGFR mutations during therapy. Our validation cohort consisted of an external dataset of 73 patients with a ctDNA profile suggestive of prior anti-EGFR exposure and serial sampling. A separate retrospective cohort of 80 patients was used to evaluate overall response rate and progression free survival during re-challenge therapies. RESULTS: Our analysis showed that RAS and EGFR relative mutant allele frequency decays exponentially (r2=0.93 for RAS; r2=0.94 for EGFR) with a cumulative half-life of 4.4 months. We validated our findings using an external dataset of 73 patients with a ctDNA profile suggestive of prior anti-EGFR exposure and serial sampling, confirming exponential decay with an estimated half-life of 4.3 months. A separate retrospective cohort of 80 patients showed that patients had a higher overall response rate during re-challenge therapies after increasing time intervals, as predicted by our model. CONCLUSION: These results provide scientific support for anti-EGFR re-challenge and guide the optimal timing of re-challenge initiation.

Colorectal premalignancy is associated with consensus molecular subtypes 1 and 2.

Background: Gene expression-based profiling of colorectal cancer (CRC) can be used to identify four molecularly homogeneous consensus molecular subtype (CMS) groups with unique biologic features. However, its applicability to colorectal premalignant lesions remains unknown. Patients and methods: We assembled the largest transcriptomic premalignancy dataset by integrating different public and proprietary cohorts of adenomatous and serrated polyps from sporadic (N = 311) and hereditary (N = 78) patient populations and carried out a comprehensive analysis of carcinogenesis pathways using the CMS random forest (RF) classifier. Results: Overall, transcriptomic subtyping of sporadic and hereditary polyps revealed CMS2 and CMS1 subgroups as the predominant molecular subtypes in premalignancy. Pathway enrichment analysis showed that adenomatous polyps from sporadic or hereditary cases (including Lynch syndrome) displayed a CMS2-like phenotype with WNT and MYC activation, whereas hyperplastic and serrated polyps with CMS1-like phenotype harbored prominent immune activation. Rare adenomas with CMS4-like phenotype showed significant enrichment for stromal signatures along with transforming growth factor-ß activation. There was a strong association of CMS1-like polyps with serrated pathology, right-sided anatomic location and BRAF mutations. Conclusions: Based on our observations made in premalignancy, we propose a model of pathway activation associated with CMS classification in colorectal carcinogenesis. Specifically, while adenomatous polyps are largely CMS2, most hyperplastic and serrated polyps are CMS1 and may transition into other CMS groups during evolution into carcinomas. Our findings shed light on the transcriptional landscape of premalignant colonic polyps and may help guide the development of future biomarkers or preventive treatments for CRC.

HELICOBACTER PYLORI INFECTION AND IMMUNE PROFILE OF PATIENTS WITH DIFFERENT GASTRODUODENAL DISEASES.

BACKGROUND: The association between infection with Helicobacter pylori and different gastroduodenal diseases is related to bacterial, host and environmental factors. Studies have demonstrated an association between the genetic diversity of H. pylori, especially in the vacA and cagA genes, and the development of digestive diseases such as peptic ulcer and gastric cancer. In addition, the nature of the host inflammatory response may explain these different manifestations of infection caused by this microorganism. In this respect, host factors that regulate the immune and inflammatory responses involving the functional interaction of H. pylori infection with different components of the immune system, particularly T cells, in gastroduodenal diseases still need further investigation. OBJECTIVE: To characterize the immune response, including immunity induced by infection with H. pylori, especially virulent strains (vacA alleles and cagA gene), by analyzing the cytokine profile and T-cell population present in gastroduodenal diseases in a Brazilian population. METHODS: In a prospective study, gastric biopsies were collected from 554 patients with different gastroduodenal diseases for histological analysis and for the determination of bacterial genotype and cytokine production (IL-4, IL-10, IFN-γ and IL-12) by ELISA. RESULTS: The predominant genotype of the H. pylori strains isolated from the patients studied was s1m1cagA+, which was more common among patients with gastric ulcer, duodenal ulcer and gastric cancer. A significant association was observed between the s1m1cagA+ genotype and a higher degree of inflammation, higher neutrophil activity and the development of intestinal metaplasia. The gastric concentrations of IFN-γ and IL-12 were significantly higher in patients infected with H. pylori than in uninfected individuals. Higher levels of these cytokines were detected in patients with gastric ulcer and cancer, while the levels of IL-4 and IL-10 in the gastric mucosa were lower in these patients. In addition, IFN-γ and IL-12 concentrations in gastric biopsies were higher in patients infected with the virulent s1m1cagA+ genotype. In contrast, IL-4 and IL-10 levels were higher in tissue infected with s2m2cagA in gastric biopsies. CONCLUSION: Our study shows that the interaction between the type of infectious strain and the Th1 immune response can influence and perpetuate gastric inflammation, and thus contributes to the development of the different clinical manifestations of H. pylori infection.

Infecção pelo Helicobacter pylori e perfil imunológico em pacientes com diferentes doenças gastroduodenais / Helicobacter pylori infection and immune profile of patients with different gastroduodenal diseases

ABSTRACT BACKGROUND: The association between infection with Helicobacter pylori and different gastroduodenal diseases is related to bacterial, host and environmental factors. Studies have demonstrated an association between the genetic diversity of H. pylori, especially in the vacA and cagA genes, and the development of digestive diseases such as peptic ulcer and gastric cancer. In addition, the nature of the host inflammatory response may explain these different manifestations of infection caused by this microorganism. In this respect, host factors that regulate the immune and inflammatory responses involving the functional interaction of H. pylori infection with different components of the immune system, particularly T cells, in gastroduodenal diseases still need further investigation. OBJECTIVE: To characterize the immune response, including immunity induced by infection with H. pylori, especially virulent strains (vacA alleles and cagA gene), by analyzing the cytokine profile and T-cell population present in gastroduodenal diseases in a Brazilian population. METHODS: In a prospective study, gastric biopsies were collected from 554 patients with different gastroduodenal diseases for histological analysis and for the determination of bacterial genotype and cytokine production (IL-4, IL-10, IFN-γ and IL-12) by ELISA. RESULTS: The predominant genotype of the H. pylori strains isolated from the patients studied was s1m1cagA+, which was more common among patients with gastric ulcer, duodenal ulcer and gastric cancer. A significant association was observed between the s1m1cagA+ genotype and a higher degree of inflammation, higher neutrophil activity and the development of intestinal metaplasia. The gastric concentrations of IFN-γ and IL-12 were significantly higher in patients infected with H. pylori than in uninfected individuals. Higher levels of these cytokines were detected in patients with gastric ulcer and cancer, while the levels of IL-4 and IL-10 in the gastric mucosa were lower in these patients. In addition, IFN-γ and IL-12 concentrations in gastric biopsies were higher in patients infected with the virulent s1m1cagA+ genotype. In contrast, IL-4 and IL-10 levels were higher in tissue infected with s2m2cagA in gastric biopsies. CONCLUSION: Our study shows that the interaction between the type of infectious strain and the Th1 immune response can influence and perpetuate gastric inflammation, and thus contributes to the development of the different clinical manifestations of H. pylori infection.

RESUMO CONTEXTO: A associação da infecção por Helicobacter pylori com diferentes doenças gastroduodenais pode estar associada a fatores bacterianos, do hospedeiro e do ambiente. Nesse contexto, estudos têm demonstrado que a diversidade genética do H. pylori, sobretudo nos genes vacA e cagA, está associada ao desenvolvimento de doenças gastroduodenais como a úlcera péptica e o câncer gástrico. Além disso, a natureza da resposta inflamatória do hospedeiro pode explicar essas diferentes manifestações da infecção por esse microrganismo. Portanto, fatores do hospedeiro que regulam as respostas imunológica e inflamatória, envolvendo a interação funcional da infecção por H. pylori com diferentes membros do compartimento imunológico, especialmente respostas imunes de células T nas doenças gastroduodenais, ainda precisam ser melhor estudados. OBJETIVO: Caracterizar a resposta imune, incluindo imunidade induzida por infecção pelo H. pylori, especialmente com cepas virulentas de H. pylori (alelos vacA e gene cagA), através da análise do perfil de citocinas e da caracterização da população de células T presentes em doenças gastroduodenais em nossa população. MÉTODOS: Em um estudo prospectivo, foram coletadas biópsias gástricas de 554 pacientes portadores das diferentes doenças gastroduodenais. Nas amostras biológicas destes pacientes foi realizada a determinação do genótipo bacteriano e a detecção das citocinas IL-4, IL-10, INF-γ e IL-12 através do método Elisa. Foram obtidas biópsias gástricas para avaliação histológica. RESULTADOS: Observamos que o genótipo predominante nas cepas de H. pylori isoladas dos pacientes estudados foi s1m1cagA positivo, sendo mais frequentes entre os pacientes com úlcera gástrica, úlcera duodenal e câncer gástrico. Houve associação significativa das cepas com o genótipo s1m1cagA positivo com maior grau de inflamação, atividade neutrofílica e desenvolvimento de metaplasia intestinal. As concentrações gástricas de INF-γ e IL-12 foram significativamente mais elevadas em pacientes infectados pelo H. pylori do que nos não infectados. Foram detectados níveis mais elevados dessas citocinas nos portadores de úlcera e câncer gástrico, sendo que nesses pacientes foram observados níveis mais baixos de IL-4 e IL-10 na mucosa gástrica. Além disso, as concentrações de INF-γ e IL-12 em biópsias gástricas, foram mais elevadas nos pacientes portadores das cepas bacterianas virulentas s1m1cagA+. Contrariamente, os níveis de IL-4 e IL-10 foram maiores em tecido infectado por cepas s2m2cagA. Pacientes com maior grau de inflamação, de atividade neutrofílica e presença de metaplasia intestinal, apresentaram níveis mais elevados de INF-γ e IL-12 e uma concentração mais baixa de IL-4 e IL-10 nas biópsias gástricas. CONCLUSÃO: Nosso estudo demonstra que a interação entre o tipo de cepa infectante e resposta imunológica com perfil Th1, podem influenciar e perpetuar a inflamação gástrica contribuindo para o desenvolvimento de diferentes manifestações clínicas na infecção pelo H. pylori.

Phase II study of nab-paclitaxel in refractory small bowel adenocarcinoma and CpG island methylator phenotype (CIMP)-high colorectal cancer.

Background: Hypermethylation of promoter CpG islands [CpG island methylator phenotype (CIMP)] represents a unique pathway for the development of colorectal cancer (CRC), characterized by lack of chromosomal instability and a low rate of adenomatous polyposis coli (APC) mutations, which have both been correlated with taxane resistance. Similarly, small bowel adenocarcinoma (SBA), a rare tumor, also has a low rate of APC mutations. This phase II study evaluated taxane sensitivity in SBA and CIMP-high CRC. Patients and methods: The primary objective was Response Evaluation Criteria in Solid Tumors version 1.1 response rate. Eligibility included Eastern Cooperative Oncology Group performance status 0/1, refractory disease, and SBA or CIMP-high metastatic CRC. Nab-paclitaxel was initially administered at a dose of 260 mg/m2 every 3 weeks but was reduced to 220 mg/m2 owing to toxicity. Results: A total of 21 patients with CIMP-high CRC and 13 with SBA were enrolled from November 2012 to October 2014. The efficacy-assessable population (patients who received at least three doses of the treatment) comprised 15 CIMP-high CRC patients and 10 SBA patients. Common grade 3 or 4 toxicities were fatigue (12%), neutropenia (9%), febrile neutropenia (9%), dehydration (6%), and thrombocytopenia (6%). No responses were seen in the CIMP-high CRC cohort and two partial responses were seen in the SBA cohort. Median progression-free survival was significantly greater in the SBA cohort than in the CIMP-high CRC cohort (3.2 months compared with 2.1 months, P = 0.03). Neither APC mutation status nor CHFR methylation status correlated with efficacy in the CIMP-high CRC cohort. In vivo testing of paclitaxel in an SBA patient-derived xenograft validated the activity of taxanes in this disease type. Conclusion: Although preclinical studies suggested taxane sensitivity was associated with chromosomal stability and wild-type APC, we found that nab-paclitaxel was inactive in CIMP-high metastatic CRC. Nab-paclitaxel may represent a novel therapeutic option for SBA.

Relación entre la grasa corporal y la expresión de ira en personas que realizan ejercicio regularmente / Relacionamento entre gordura corporal e expressão de raiva em pessoas que se exercitam regularmente / Relationship between body fat mass and the expression of anger in people who practice exercise customarily

La actividad física proporciona beneficios, tanto a la población sana como enferma, pero también puede derivar en problemas psicológicos y emocionales como respuesta al estrés. Además, aquellos atletas con menor peso corporal presentan indicadores más elevados de depresión e ira. Se plantea determinar la relación de la grasa corporal sobre la expresión de ira y entender la relación entre distintos comportamientos psicológicos, en personas físicamente activas. 264 sujetos cumplimentaron el Inventario de Expresión de Ira Estado-Rasgo, versión 2, para el estudio sobre las características de la ira y sus efectos en la salud mental y física. Se tomaron medidas antropométricas (peso, talla, IMC, porcentaje de grasa corporal, masa libre de grasa). Se calcularon distintos percentiles en función del género y edad, clasificando a los participantes en tres grupos: percentil 55 de grasa corporal. Se analizaron distintos comportamientos en relación al STAXI-2 y a los distintos percentiles, pero sin encontrar diferencias significativas entre la ira y los tres grupos (AU)

Physical activity provides benefits, both to healthy as to ill population, but can also lead to psychological and emotional problems in response to stress. Furthermore, those athletes with lower body weight have higher indicators of depression and anger. We propose to relate body fat on the expression of anger and to understand the relationship between different psychological behaviors in physically active people. 264 subjects completed the Anger Expression Inventory State Trait version 2 (STAXI-2), which studies the characteristics of anger and its effects on mental and physical health. Anthropometric measurements (weight, height, BMI, percent body fat, fat-free mass) were taken. Various body fat percentiles, 55 were calculated according to gender and age, classifying participants into three percentile groups. Different behaviors were recorded in relation to STAXI-2 and percentiles, but with no significant differences between anger and those groups (AU)

A atividade física proporciona benefícios tanto para pessoas saudáveis como doentes, mas também pode levar a problemas psicológicos e emocionais, como resposta ao estresse. Além disso, os atletas com menor peso corporal têm indicadores mais altos de depressão e raiva. Prevê-se a determinar a influência da gordura corporal sobre a modulação do comportamento e entender a relação entre os vários comportamentos psicológicos entre as pessoas fisicamente ativas. 264 pessoas preencheram um questionário ad hoc, que incluiu Anger Expression Inventory State Trait version 2 (STAXI-2). Medidas antropométricas (peso, altura, IMC, percentual de gordura corporal, massa livre de gordura) foram tomadas. Vários percentis foram calculados por sexo e idade, classificando os participantes em três grupos: percentil 55 de gordura corporal. Diferentes comportamentos foram registrados em relação ao STAXI-2 e os vários percentis, mas sem diferenças significativas entre a raiva e os três grupos (AU)

Exceso ponderal infantil y adolescente: factores modificables, herencia genética y percepción de la imagen corporal / Excess weight in children and adolescents: modifiable factors, genetic inheritance and body image perception

Introducción: el sobrepeso y obesidad alcanzan una alta prevalencia entre niños y adolescentes en España. Los hábitos modificables, la carga genética y la percepción del peso empeoran con los años, convirtiendo a los niños en adultos con sobrepeso. Se analizó la relevancia de distintos factores modificables (hábitos alimentarios, actividad física, sedentarismo y horas de sueño), la herencia genética, así como la percepción de su imagen corporal, en el exceso ponderal de niños y adolescentes. Material y métodos: estudio observacional retrospectivo de 101 escolares de Madrid (edad media de diez años), con recogida de datos antropométricos (peso, talla, pliegues cutáneos y circunferencia de cintura), dietéticos (KidMed®), de actividad física (IPAQ® adaptado), sedentarismo, horas de sueño y percepción del peso e imagen corporal. Resultados: el 31% de los niños presentaba exceso ponderal. Un 53,4% necesitaba mejorar la dieta. Fue mayor el número de participantes con normopeso que no seguían una alta adherencia a la dieta mediterránea que aquellos con sobrepeso-obesidad que sí se adherían. No se observó correlación estadísticamente significativa entre el estado ponderal (según el percentil de peso) y las características corporales de los padres, pero sí en función del índice de masa corporal (IMC).A un 70% de obesos y un 50% de desnutridos les gustaría pesar lo mismo. Conclusiones: los factores modificables no se relacionaron con un mayor exceso ponderal. El peso de los progenitores tuvo influencia en el estado ponderal de los hijos, aunque no se obtuvieron resultados estadísticamente significativos al analizar los factores modificables y la herencia en conjunto (AU)

Introduction: overweight and obesity achieve a high prevalence among children and adolescents in Spain. Modifiable habits, combined with the genetic load and weight perception, declines over the years making children overweight adults. Our aim was to analyze the relevance in excess weight of various modifiable factors (dietary habits, physical activity, sedentary lifestyle and sleep), heredity and body image perception in children and adolescents. Methods: a retrospective observational study of 101 schoolchildren in Madrid (mean age 10 years) was performed with collection of anthropometric (weight, height, skinfold thickness and waist circumference), dietary (KidMed), physical activity (IPAQ adapted), sedentary lifestyle, sleep and perception of weight and body image data. Results: 31% of children had excess weight. 53.4% ​​needed diet improvement. The number of participants with normal weight who did not follow a high adherence to the Mediterranean diet was greater than those with overweight-obesity who did adhered. No statistically significant results between weight status (according to weight percentile) and body parental characteristics were obtained, but according to BMI. 70% of obese and 50% of malnourished would like to stay in their weigh. Conclusion: modifiable factors were not associated with an increased excess weight. Parents’ weight had some influence on the weight status of children, although no statistically significant results were obtained when both modifiable factors and heredity were analyzed altogether (AU)