Sequential RAS mutations evaluation in cell-free DNA of patients with tissue RAS wild-type metastatic colorectal cancer: the PERSEIDA (Cohort 2) study.

PURPOSE: RAS (KRAS/NRAS) mutational status on a tumor biopsy is mandatory to guide the best treatment in metastatic colorectal cancer (mCRC). Determining the RAS mutational status by tumor-tissue biopsy is essential in guiding the optimal treatment decision for mCRC. RAS mutations are negative predictive factors for the use of EGFR monoclonal antibodies. Cell-free DNA (cfDNA) analysis enables minimally invasive monitoring of tumor evolution. METHODS/PATIENTS: PERSEIDA was an observational, prospective study assessing cfDNA RAS, BRAF and EGFR mutations (using Idylla™) in first-line mCRC, RAS wild-type (baseline tumor-tissue biopsy) patients (cohort 2). Plasma samples were collected before first-line treatment, after 20 ± 2 weeks, and at disease progression. RESULTS: 117 patients were included (103 received panitumumab + chemotherapy as first-line treatment). At baseline, 7 (6.8%) patients had RAS mutations, 4 (3.9%) BRAF mutations and no EGFR mutations were detected (cfDNA, panitumumab + chemotherapy subpopulation [panitumumab + Ch]). The baseline RAS mutational status concordance between tissue and liquid biopsies was 94.0% (93.2%, panitumumab + Ch). At 20 weeks, only one patient in the study (included in the panitumumab + Ch) had an emerging cfDNA RAS mutation. No emerging BRAF or EGFR mutations were reported. At disease progression, 6 patients had emergent mutations not present at baseline (RAS conversion rate: 13.3% [6/45]; 15.0% [6/40], panitumumab + Ch). CONCLUSIONS: The concordance rate between liquid and solid biopsies at baseline was very high, as previously reported, while our results suggest a considerable emergence of RAS mutations during disease progression. Thus, the dynamics of the genomic landscape in ctDNA may provide relevant information for the management of mCRC patients.

Efficacy and safety of chemotherapy in young patients with advanced gastroesophageal adenocarcinoma: data from the Spanish AGAMENON-SEOM registry.

BACKGROUND: Gastroesophageal adenocarcinoma in young adults (GCYA) counts for 10-15% of diagnoses. Previous studies have mainly focused on surgical outcomes in patients with resectable tumors; however, systemic therapy for advanced GCYA remains under-evaluated. This study aims to assess the efficacy-related outcomes and safety of first-line chemotherapy (CT) in younger versus older patients with advanced gastroesophageal adenocarcinoma. METHODS: Patients with advanced gastroesophageal adenocarcinoma from the AGAMENON-SEOM registry treated with first-line polychemotherapy between January 2008 and October 2022 were included. We compared clinicopathological features, therapies received, efficacy-related outcomes, and toxicity between individuals aged < and ≥ 45 years. RESULTS: Out of 3386 patients, 263 (7.8%) were < 45 years. Young patients exhibited a higher proportion of females affected, lower ECOG-PS ≥ 2, fewer comorbidities, and more aggressive disease-related features, such as higher proportion of diffuse subtype, signet-ring cells, plastic linitis, grade 3, peritoneal metastases and metastatic disease at diagnosis. They received more triple-agent combinations and underwent more surgeries in metastatic setting. No significant differences were observed between groups in overall response rate (53.1% vs. 52.3% in < and ≥ 45 years, respectively, p = 0.579), progression-free survival (6.1 vs. 6.83 months, p = 0.158) and overall survival (11.07 vs. 10.81 months, p = 0.82), even after adjusting for potential confounding factors. Grade 3-4 adverse events were comparable in both groups, although toxicity leading to treatment discontinuation was more frequent in older patients. CONCLUSIONS: In the AGAMENON-SEOM registry, younger patients with GCYA exhibited more aggressive clinicopathological features, and despite receiving more aggressive treatments, similar efficacy outcomes and toxicity profiles were achieved compared to their older counterparts. In the AGAMENON-SEOM registry, GEAC in < 45 years showed more aggressive clinicopathological features and, although treated with more intense first-line CT regimens, similar efficacy outcomes and toxicity were achieved compared to older patients.

Maternal consumption and perinatal exposure to non-nutritive sweeteners: should we be concerned?

The context for this review is the rapid increase in the use of non-nutritive sweeteners (NNSs) instead of sugar in foods and beverages, a situation so prevalent in some countries that consumers are finding it increasingly challenging to access foods without NNSs. The benefits of consuming NNSs on obesity and diabetes are now being questioned, and studies have shown that they may exert physiological activities, sometimes independently of sweet taste receptor stimulation. Few studies, limited mainly to North American and European countries, have described the consumption of NNSs by pregnant or lactating women and infants. Most focus on beverages rather than foods, but all agree that consumption levels have increased dramatically. Although some studies report a negative impact of NNSs on the risk of preterm birth, increased birth weight and decreased gestational age, the level of evidence is low. Several studies have also reported increased weight gain in infancy, associated with maternal NNS intake. Interestingly, several NNSs have been detected in amniotic fluid and breast milk, usually (but not always) at concentrations below their established detection limit in humans. Unfortunately, the impact of chronic exposure of the fetus/infant to low levels of multiple NNSs is unknown. In conclusion, there is a stark contrast between the galloping increase in the consumption of NNSs and the small number of studies evaluating their impact in at-risk groups such as pregnant and lactating women and infants. Clearly, more studies are needed, especially in Latin America and Asia, to fill these gaps and update recommendations.

Development and Relative Validation of a Food Frequency Questionnaire to Assess Non-Nutritive Sweeteners Intake among Pregnant Women in Santiago, Chile: A Pilot Study.

Studies on the effects of non-nutritive sweeteners (NNSs) among pregnant women are scarce and have produced mixed results. One of the major challenges is to accurately assess NNS intake, especially in countries that have implemented policies to prevent obesity and where many foods and beverages have been progressively reformulated to partially or totally replace sugar with NNSs. This study aimed to develop and assess the relative validity of a food frequency questionnaire (FFQ) for use in pregnant women. We developed an FFQ to examine the intake of seven NNSs (acesulfame-k, aspartame, cyclamate, saccharin, sucralose, steviol glycosides, and D-tagatose). This questionnaire was piloted in 29 pregnant women (median age = 31.2 y; 25th-75th percentile: 26.9-34.7) to assess NNS intake over the previous month, compared to 3-day dietary records (3-DR). The validity of this dietary method was assessed using Spearman's correlation coefficient, Lin´s concordance correlation coefficient (CCC), and Bland-Altman plots. Spearman's correlations between the FFQ on NNSs and 3-DR ranged from 0.50 for acesulfame K to 0.83 for saccharin. CCC ranged between 0.22 and 0.66. The Bland-Altman plots showed an overestimation of saccharin, sucralose, and steviol glycosides intake by the FFQ on NNSs compared with 3-DR, and an underestimation of acesulfame K and aspartame. Overall, the NNSs most frequently consumed were sucralose, and none of the participants exceeded the acceptable daily intake for any of the NNSs evaluated. The FFQ on NNSs seems to be reasonably valid in the assessment of NNSs among pregnant women.

Evolution of RAS Mutations in Cell-Free DNA of Patients with Tissue RAS Wild-Type Metastatic Colorectal Cancer Receiving First-Line Treatment: The PERSEIDA Study.

The serial analysis of cell-free DNA (cfDNA) enables minimally invasive monitoring of tumor evolution, providing continuous genetic information. PERSEIDA was an observational, prospective study assessing the cfDNA RAS (KRAS/NRAS) mutational status evolution in first-line, metastatic CRC, RAS wild-type (according to baseline tumor tissue biopsy) patients. Plasma samples were collected before first-line treatment, after 20 ± 2 weeks, and at disease progression. One hundred and nineteen patients were included (102 received panitumumab and chemotherapy as first-line treatment-panitumumab subpopulation). Fifteen (12.6%) patients presented baseline cfDNA RAS mutations (n = 14 [13.7%], panitumumab subpopulation) (mutant allele fraction ≥0.02 for all results). No patients presented emergent mutations (cfDNA RAS mutations not present at baseline) at 20 weeks. At disease progression, 11 patients (n = 9; panitumumab subpopulation) presented emergent mutations (RAS conversion rate: 19.0% [11/58]; 17.7% [9/51], panitumumab subpopulation). In contrast, three (5.2%) patients presenting baseline cfDNA RAS mutations were RAS wild-type at disease progression. No significant associations were observed between overall response rate or progression-free survival and cfDNA RAS mutational status in the total panitumumab subpopulation. Although, in patients with left-sided tumors, a significantly longer progression-free survival was observed in cfDNA RAS wild-type patients compared to those presenting cfDNA RAS mutations at any time. Continuous evaluation of RAS mutations may provide valuable insights on tumor molecular dynamics that can help clinical practice.

Contribución de las organizaciones sociales "ollas comunes" a la alimentación de la población chilena en tiempos de pandemia por COVID-19

RESUMEN Las "ollas comunes" (OC) son organizaciones sociales temporales que entregan alimentación gratuita en periodos de crisis. En Chile, resurgen el año 2020 a raíz de la pandemia del COVID-19, y si bien han aparecido en otros períodos de la historia, no ha sido cuantificada su contribución. El objetivo de este estudio fue determinar su contribución a la alimentación y nutrición de las/os chilenas/os, mediante la caracterización y análisis de su oferta alimentaria. Se realizó un estudio descriptivo mediante la aplicación de una encuesta online a voluntarias/os de todo el territorio nacional, la cual incluyó una caracterización del encuestado/a, de la OC que representa y de las preparaciones ofrecidas, en base a lo cual se obtuvo el aporte calórico y nutricional. Contestaron 117 OC (5,1% zona norte, 85,5% centro y 9,4% sur) cuya contribución principal fue con almuerzos (95,9%) con una mediana de 150 (p25: 100 - p75: 200) raciones diarias, compuestas por plato de fondo (95,9%), pan (80,5%) y ensalada (74,8%). Las preparaciones más prevalentes fueron legumbres (91,1%), arroz (78%) y fideos (77,2%). Estos almuerzos aportaron en promedio un 23% del requerimiento energético diario y aportan con el 35% del requerimiento de fibra, pero su aporte en vitamina B12, zinc y hierro fue bajo respecto del requerimiento y aporte esperado para el tiempo de comida. Hasta la fecha, estos datos son los primeros publicados sobre el tema, siendo útiles para determinar su aporte a la seguridad alimentaria del país en tiempos de crisis.

ABSTRACT "Communal Pots" (CP) are temporary social organizations that provide free food in times of crisis. In Chile, as a result of the COVID-19 pandemic, in 2020 the CP resurfaced and, although they have appeared in other periods of history, how they benefitted the population is unknown. The objective of this study is to determine the contribution of the CP to the diet and nutrition of Chileans, through the characterization and analysis of their food supply. For this, a descriptive study was carried out based on an online survey sent to volunteers from all over the country after signing the informed consent. The survey included characterization of the respondent and the CP they represented, the preparations offered by the CP, based on which the caloric and nutritional contribution was obtained. In total, 117 CP answered; 5.1% from the north, 85.5% from the center and 9.4% from the south of Chile. Their main contribution was providing lunches (95.9%) with a median of 150 (p25: 100 - p75: 200) daily rations, made up of a main entree (95.9%), bread (80.5%) and salad (74.8%). The most popular preparations were legumes (91.1%), rice (78%) and noodles (77.2%). These lunches provide an average of 23% of the daily energy requirement and 35% of the fiber requirement, but their contribution of vitamin B12 (2.5%), zinc (25%) and iron (28% req. woman) was low regarding the requirement and expected contribution for the meal time. To date, these data are the first published, to report on the real influence of this social movement in the country's food security in times of crisis.

Overuse of Non-caloric Sweeteners in Foods and Beverages in Chile: A Threat to Consumers' Free Choice?

The prevalence of obesity among Chilean adults and children is one of the highest worldwide. To fight the constant increase of non-communicable diseases and the growing sales of sugar-sweetened beverages, the Chilean government recently enacted a new Law of Food Labeling and Advertising imposing the application of front-of-package warning labels in foodstuffs whose composition exceeds limits for critical nutrients including sugar. Accordingly, food companies have been reformulating their products, incorporating non-caloric sweeteners (NCSs) in partial or total replacement of sucrose. The number of NCS-containing foods and beverages, therefore, has been increasing in the last years. This study aims to identify the NCS-containing products from different food/beverage categories currently available on the Chilean market. Nineteen supermarkets and 13 food web pages were visited by trained dietitians to carry out a systematic search of ingredient information from the different food categories. Overall, 1,489 products were analyzed, of which 815 (55.5%) contained at least one NCS, being this proportion particularly high, compared to other countries. 67.1% of the dairy products, 31.5% of the cereal products, 49% of the processed fruits, 74.3% of the non-alcoholic beverages, and 46.2% of sweets and other desserts contained NCS. Considering the food categories more specifically oriented to children, NCSs were present in 98.8% of powder juices, 98.3% of the flavored milks, 91.2% of jellies, and 79% of the dairy desserts. Sucralose and steviol glycosides were the most widely used NCSs, these sweeteners being present, alone or mixed with other, in 73.5 and 39.7% of the NCS-containing products, respectively, while the use of saccharin and cyclamate was low. In addition, 80 tabletop NCSs were available in the local market, 91.2% of them being sucralose and steviol glycosides (alone or combined). The high number of food products containing steviol glycosides makes very plausible that the daily consumption of this NCS in the pediatric populations could exceed its acceptable daily intake (ADI). The fact that there are no NCS-free foods alternatives for certain food categories, especially for children, is worrying.

Sistema de porciones de intercambio de alimentos en Chile y el mundo: historia, usos y consideraciones / Food portion exchange lists in Chile and the world: history, uses and considerations

El sistema de porciones de intercambio es una metodología sencilla y rápida que se utiliza para entregar indicaciones alimentarias a usuarios sanos y con patologías. Se realizó una revisión bibliográfica para actualizar conceptos y evaluar la vigencia de su uso y sus aplicaciones. El sistema es ampliamente usado en diferentes países, incluyendo Chile, existiendo distintos tipos de listas de alimentos y preparaciones según la metodología de la definición de las porciones, o bien según diversidad y número de alimentos presentes. Su uso es mayormente con fines asistenciales, siendo también útil en educación comunitaria y docencia. En Chile, los listados de porciones intercambiables fueron publicados el año 1999 y no se han actualizado hasta la fecha. Razones como el cambio en el perfil epidemiológico, mayor acceso a la información y la diversificación de alimentos en la dieta, hace necesario una revisión in extenso de los listados nacionales, con el fin de incorporar mayor diversidad de alimentos y preparaciones típicas a tan masiva y necesaria herramienta técnica, que es fundamental para el profesional Nutricionista y un aporte a la salud y a la cultura de los países.

The food portion exchange list is a simple and fast methodology that is used to give dietary indications to healthy and sick users. A review was carried out to update concepts and evaluate the current state of the exchange list used and their application. The system is widely used in different countries, including Chile, there are different types of foods or preparations exchange lists that use different methodologies for the definition of portions, according to the diversity and number of foods present. Its use is mainly for healthcare purposes, being also useful in community education and college teaching. In Chile, the food portion exchange lists were published in 1999 and have not been updated since. Reasons such as the change in the epidemiological profile, greater access to information and the diversification of foods in the diet, make necessary an in-depth review of the national lists, in order to incorporate a greater diversity of foods and typical preparations. Exchange lists are a necessary technical tool fundamental for nutrition professionals and contribute to the health and culture of countries.

Indicadores de transformación de alimentos consumidos en Chile para su uso en planificación de minutas / Food processing indicators consumed in Chile for use in menu planning

Muchos de los alimentos consumidos a diario sufren previamente algún grado de transformación, desde mínimas operaciones de limpieza hasta cambios mayores producto de la cocción. Estas operaciones culinarias pueden afectar el volumen y/o peso de los alimentos, lo que implica una diferencia entre lo adquirido y lo realmente servido al plato. Algunos alimentos pierden gramaje mientras otros lo aumentan, dependiendo del alimento y del tipo y condiciones de la operación culinaria aplicada. Lo anterior influye en la planificación de minutas afectando el presupuesto y las raciones servidas. Para considerar estas variaciones se deben aplicar los indicadores de transformación de alimentos (ITA) que cuantifican las pérdidas por operaciones preliminares y los cambios generados por la cocción. El objetivo de este estudio fue obtener los ITA para distintos alimentos consumidos en Chile bajo diferentes operaciones culinarias. Para ello los alimentos fueron pesados, en bruto y neto, luego de lo cual se calcularon sus ITA correspondientes. Los indicadores obtenidos representan una estandarización nacional, no publicada previamente, cuya principal utilidad es la planificación de minutas, aunque también contribuyen a afinar el cálculo de la composición química de alimentos y preparaciones y al análisis de encuestas de consumo, lo que representa un aporte al área de alimentos y alimentación colectiva en Chile(AU)

Many of the foods we eat suffer some grade of previous transformation, which can go from minimal cleaning operations to major transformations resulting from the application of heat. These actions produce a change in the volume and / or weight of the food, which implies a variation between the food that is acquired or bought and the food that is actually served and / or consumed. These variations could result in loss or gain in weight, depending on the type of food and the type and conditions of the culinary operation applied. On the other hand, these variations have implications in the planning of the menus since they can affect the budget and the quantities of the portion presented in the plate. In order to take these changes into account, the food transformation indices (ITA) must be applied, which consider losses due to preliminary operations and changes generated by cooking processes. The aim of this study was to obtain the different ITAs resulting from culinary operations carried out on food consumed in Chile. For this, the food was weighed, gross and net, calculating for each one the corresponding ITA. The indicators obtained represent a national standardization, not previously published, whose greatest usefulness is the planning of menus, although they are also useful in calculating the chemical composition of food and meals, and for intake survey analysis, being a contribution to the food area and the area of collective food in Chile(AU)

Manejo de vía aérea difícil en pacientes con malformaciones craneofaciales / Management of difficult airway in patients with craniofacial malformations

El manejo de la vía aérea representa un reto constante en la práctica de la anestesiología pediátrica, más aun en los pacientes que presentan vía aérea difícil anticipada como son los pacientes pediátricos con malformaciones craneofaciales. En paciente con vía aérea difícil como lo son los pacientes con malformaciones craneofaciales se considera el uso de fibroscopia flexible como el gold standard en la intubación, sin embargo la traqueostomía es una opción que debe considerarse en todos los casos de vía aérea difícil. A continuación se presenta una revisión bibliográfica en la que se expone el manejo de la vía aérea dificil comprendiendo las variaciones anatómicas y fisiológicas como las que se presentan en los pacientes con síndrome de Goldenhar y síndrome Nager.

Airway management represents a constant challenge in the practice of pediatric anesthesiology, even more so in patients who present difficult airways as are pediatric patients with craniofacial malformations. In patients with difficult airways such as patients with craniofacial malformations, the use of flexible fibroscopy as the gold standard in intubation is considered, but tracheostomy is an option that should be considered in all cases of difficult airway. The following is a bibliographic review in which the management of the airway is difficult, including anatomical and physiological variations such as those present in patients with Goldenhar syndrome and Nager syndrome.

Anestesia en un paciente con Síndrome de Gilbert: a propósito de un casoANESTESIA EN UN PACIENTE CON SÍNDROME DE GILBERT: A PROPÓSITO DE UN CASO / Anesthesia in a patient with Gilbert's syndrome: a case report

El síndrome de Gilbert es una enfermedad benigna y hereditaria causada por la deficiencia relativa de la enzima glucuronil transferasa que es la causa más común de hiperbilirrubinemia congénita y que manifiesta clínicamente con ictericia, que puede aparecer antes, durante o después de la anestesia. Presentamos el manejo anestésico del caso de un paciente joven con síndrome de Gilbert que fue intervenido de amigdalectomía bajo anestesia general. Los fármacos y medicamentos anestésicos que utilizan esta enzima para su metabolismo o excreción deben ser evitados para minimizar el estrés hepático durante el período perioperatorio y permitir una conducción segura de la anestesia y evitar la icteria en estos pacientes.

Gilbert syndrome is a benign and hereditary disease caused by the relative deficiency of the enzyme glucuronyl transferase which is the most common cause of congenital hyperbilirubinemia and which manifests clinically with jaundice, which may appear before, during or after anesthesia. We present the anesthetic management of the case of a young patient with Gilbert's syndrome who underwent laparoscopic cholecystectomy under general anesthesia. Anesthetic drugs and drugs that use this enzyme for its metabolism or excretion should be avoided to minimize hepatic stress during the perioperative period and allow safe conduction of anesthesia and avoid jaundice in these patients.

Modulation of Helicobacter pylori colonization with cranberry juice and Lactobacillus johnsonii La1 in children.

OBJECTIVE: Probiotics and cranberry have been shown to inhibit Helicobacter pylori in vitro owing to bacteriocin production and high levels of proanthocyanidins, respectively. These effects have been confirmed in clinical trials with H. pylori-positive subjects. The aim of this study was to evaluate whether regular intake of cranberry juice and the probiotic Lactobacillus johnsonii La1 (La1) may result in an additive or synergistic inhibition of H. pylori in colonized children. METHODS: A multicentric, randomized, controlled, double-blind trial was carried out in 295 asymptomatic children (6-16 y of age) who tested positive for H. pylori by (13)C-urea breath test (UBT). Subjects were allocated in four groups: cranberry juice/La1 (CB/La1), placebo juice/La1 (La1), cranberry juice/heat-killed La1 (CB), and placebo juice/heat-killed La1 (control). Cranberry juice (200 mL) and La1 product (80 mL) were given daily for 3 wk, after which a second UBT was carried out. A third UBT was done after a 1-mo washout in those children who tested negative in the second UBT. RESULTS: Two hundred seventy-one children completed the treatment period (dropout 8.1%). Helicobacter pylori eradication rates significantly differed in the four groups: 1.5% in the control group compared with 14.9%, 16.9%, and 22.9% in the La1, CB, and CB/La1 groups, respectively (P < 0.01); the latter group showed a slight but not significant increase when compared with the other treated groups. The third UBT was carried out only in 19 of the 38 children who tested negative in the second UBT and H. pylori was detected in 80% of them. CONCLUSION: These results suggest that regular intake of cranberry juice or La1 may be useful in the management of asymptomatic children colonized by H. pylori; however, no synergistic inhibitory effects on H. pylori colonization were observed when both foodstuffs were simultaneously consumed.

Tratamiento de la incontinencia fecal con "biofeedback" / Biofeedback treatment for fecal incontinence

El objetivo de este trabajo es determinar la eficacia de la biorretroalimentación en el tratamiento de la incontinencia fecal. Entre mayo de 1991 y mayo de 1993 se evaluaron en forma restrospectiva 36 pacientes, con una edad promedio de 58 años; 22 eran mujeres. Las causas de la incontinencia eran: idiopática en 16, trauma obstétrico en 10, post cesárea en 5 y neurológicas en 5. La técnica empleada fue de manometría anorectal y retro alimentación, complementando con un sistema de balones conectados a los esfínteres anales y a la ampolla rectal. Se evaluó la respuesta como curación, mejoría o fracaso terapéutico. 2 pacientes abandonaron el tratamiento. De los 34 restantes, 17 (50 por ciento) se curaron, 15 (44 por ciento) mejoraron y no hubo respuesta (fracaso terapéutico) en 2. Sólo el grupo de pacientes curados demostró una contracción voluntaria completa con significación clínica estadística. Este tipo de tratamiento es eficaz, no traumático y sencillo de realizar por los pacientes con incontinencia fecal

Tratamiento de la incontinencia fecal con "biofeedback" / Biofeedback treatment for fecal incontinence

El objetivo de este trabajo es determinar la eficacia de la biorretroalimentación en el tratamiento de la incontinencia fecal. Entre mayo de 1991 y mayo de 1993 se evaluaron en forma restrospectiva 36 pacientes, con una edad promedio de 58 años; 22 eran mujeres. Las causas de la incontinencia eran: idiopática en 16, trauma obstétrico en 10, post cesárea en 5 y neurológicas en 5. La técnica empleada fue de manometría anorectal y retro alimentación, complementando con un sistema de balones conectados a los esfínteres anales y a la ampolla rectal. Se evaluó la respuesta como curación, mejoría o fracaso terapéutico. 2 pacientes abandonaron el tratamiento. De los 34 restantes, 17 (50 por ciento) se curaron, 15 (44 por ciento) mejoraron y no hubo respuesta (fracaso terapéutico) en 2. Sólo el grupo de pacientes curados demostró una contracción voluntaria completa con significación clínica estadística. Este tipo de tratamiento es eficaz, no traumático y sencillo de realizar por los pacientes con incontinencia fecal (AU)