Cholecystectomy and digestive cancer in Chile: Complementary results from interrupted time series and aggregated data analyses.

Gallbladder cancer (GBC) mortality in Chile is among the highest worldwide. In 2006, the Chilean government launched a programme guaranteeing access to gallbladder surgery (cholecystectomy) for patients aged 35-49 years. We evaluated the impact of this programme on digestive cancer mortality. After conducting an interrupted time series analysis of hospitalisation and mortality data from 2002 to 2018 publicly available from the Chilean Department of Health Statistics and Information, we calculated the change in the proportion of individuals without gallbladder since 10 years. We then estimated age, gender, region, and calendar-year standardised mortality ratios (SMRs) as a function of the change in the proportion of individuals without gallbladder. The cholecystectomy rate increased by 45 operations per 100,000 persons per year (95%CI 19-72) after the introduction of the health programme. Each 1% increase in the proportion of individuals without gallbladder since 10 years was associated with a 0.73% decrease in GBC mortality (95% CI -1.05% to -0.38%), but the negative correlation was limited to women, southern Chile and age over 60. We also found decreasing mortality rates for extrahepatic bile duct, liver, oesophageal and stomach cancer with increasing proportions of individuals without gallbladder. To conclude, 12 years after its inception, the Chilean cholecystectomy programme has markedly and heterogeneously changed cholecystectomy rates. Results based on aggregate data indicate a negative correlation between the proportion of individuals without gallbladder and mortality due to gallbladder and other digestive cancers, which requires validation using individual-level longitudinal data to reduce the potential impact of ecological bias.

[Immunophenotyping by spectral cytometry reveals a profile of lymphopenia associated with deregulation with an increase in effector memory lymphocytes in a patient with a mutation in the ITPR3 gene]. / Inmunofenotipo por citometría espectral, revela un perfil de linfopenia asociado a desregulación con aumento de linfocitos de memoria efectora en paciente con mutación en el gen ITPR3.

BACKGROUND: Variants in intracellular calcium transport genes have been associated with syndromic immunodeficiencies with a SCID phenotype. CASE REPORT: Seven-year-old girl of non-consanguineous parents, in Cartagena-Colombia. At two months of age, he presented hematochezia and was diagnosed with alimentary proctolitis without improvement with restriction to milk, wheat and eggs, and malnutrition developed. At eight months, a colon biopsy shows chronic lymphoid hyperplasia, presenting with anemia, eosinophilia, but total and specific IgE to normal foods. After four years, the Immunology Service found her asymptomatic, nutritionally recovered and without allergic sensitization, but eosinophilia and elevated calprotectin persisted, suggesting an early-onset inflammatory bowel disease. Immunoglobulins were normal, lymphocyte populations with CD3, CD4 and CD8 lymphopenia. At six years old, she presented atopic dermatitis, still had elevated calprotectin and was lymphopenic. Immunophenotyping by spectral cytometry using Cytek®cFluor®Immunoprofiling-Kit14 showed lymphopenia and CD4/CD8 inversion. Naïve CD4+ and CD8+ T lymphocytes were decreased, while T-CD8+CD45RA-CCR7- and T-CD8+CD45RA+CCR7- effector memory populations were expanded. Effector and central memory CD4+ T-lymphocytes were also increased1 (Image 1). The exome revealed a heterozygous variant in the ITPR3 gene (carrier father), c.7571G>A, p.(Arg2524His); predictors classify it as having a potential eliminating effect. CONCLUSIONS: The clinical features and immunophenotype of this candidate variant differ from others related to intracellular calcium transport. They are functional studies necessary to validate their causality. A patient with a potentially deleted variant presents an immunophenotype with CD3 lymphopenia and persistent lymphocyte activation.

ANTECEDENTES: Las variantes en genes del transporte de calcio intracelular han sido asociadas a inmunodeficiencias sindrómicas con un fenotipo IDCG. REPORTE DE CASO: Niña de siete años, de padres no consanguíneos, en Cartagena-Colombia. A los dos meses de vida, presenta hematoquecia y se diagnostica con proctolitis alimentaria sin mejoría con restricción a leche, trigo y huevo, desarrollando desnutrición. A los ocho meses, una biopsia de colon muestra hiperplasia linfoide crónica, cursa con anemia, eosinofilia, pero IgE total y específica a alimentos normales. A los cuatro años, el Servicio de Inmunología la encuentra asintomática, recuperada nutricionalmente y sin sensibilización alérgica, pero persiste eosinofilia y calprotectina elevada, sugiriendo una enfermedad inflamatoria intestinal de inicio temprano. Las inmunoglobulinas fueron normales, poblaciones linfocitarias con linfopenia CD3, CD4 y CD8. A los seis años, presenta dermatitis atópica, sigue con calprotectina elevada y linfopénica. El inmunofenotipo por citometría espectral mediante Cytek®cFluor®Immunoprofiling-Kit14, mostró linfopenia e inversión CD4/CD8. Los linfocitos T-vírgenes CD4+ y CD8+ estaban disminuidos, en cambio las poblaciones de memoria efectora T-CD8+CD45RA-CCR7- y T-CD8+CD45RA+CCR7­ estaban expandidas. Los linfocitos T-CD4+ de memoria efectora y central, también estaban aumentados1 (Imagen 1). El exoma reveló una variante heterocigótica en el gen ITPR3 (padre portador), c.7571G>A, p.(Arg2524His); los predictores la clasifican como de potencial efecto deletéreo. CONCLUSIONES: La clínica y el inmunofenotipo de esta variante candidata difiere de otras relacionadas con el transporte del calcio intracelular. Son necesarios estudios funcionales para validar su causalidad. Una paciente con una variante potencialmente deletérea, presenta un inmunofenotipo con linfopenia CD3 y activación persistente de los linfocitos.

[Lifestyle modification and risk factor control in the prevention and treatment of atrial fibrillation]. / Modificaciones en el estilo de vida y control de los factores de riesgo en la prevención y el tratamiento de la fibrilación auricular.

Atrial fibrillation (AF) is the most prevalent arrhythmia and is related with significant morbidity, mortality and costs. In spite of relevant advances in the prevention of embolic events and rhythm control, little has been done to reduce its prevalence, progression and impact, since it increases with ageing as well as with common risk factors such as alcohol intake, tobacco use and stress as well as with arterial hypertension, diabetes mellitus, heart failure, sleep apnea, kidney failure, chronic pulmonary obstructive disease, ischemic heart disease and stroke, among other important comorbidities. Fortunately, new evidence suggests that lifestyle modifications and adequate risk factors and comorbidities control could be effective in primary and secondary AF prevention, especially in its paroxysmal presentations. This is why a multidisciplinary approach integrating lifestyle modifications, risk factors and comorbidities control, is necessary in conjunction with rhythm or rate control and anticoagulation. Unfortunately, that holistic approach strategy is not considered, is scarcely studied or is subtilized in general clinical practice. The present statement's objectives are to: 1) review the relationship between habits, risk factors and illnesses with AF, 2) review the individual and common physiopathology mechanisms of each one of those conditions that may lead to AF, 3) review the effect of control of habits, risk factors and co-morbidities on the control and impact of AF, and 4) supply guidelines and recommendations to start multidisciplinary and integrative AF treatment.

La fibrilación auricular (FA) es la arritmia más frecuente y se asocia con importante morbilidad, mortalidad y costos. A pesar de los grandes avances en la prevención de eventos embólicos y en el control del ritmo, poco se ha realizado para reducir su prevalencia, progresión e impacto, debido a que incrementa con la edad y con la presencia de múltiples factores de riesgo muy comunes en la población, como obesidad, sedentarismo, alcoholismo, tabaquismo y estrés, así como con hipertensión arterial sistémica, diabetes mellitus, insuficiencia cardiaca, apnea del sueño, enfermedad renal crónica, enfermedad pulmonar obstructiva crónica, cardiopatía isquémica y enfermedad vascular cerebral, entre otra comorbilidad importante. Afortunadamente, nuevas evidencias demuestran que las modificaciones en el estilo de vida y el control adecuado de los factores de riesgo y de la comorbilidad pueden ser efectivos en la prevención primaria y secundaria de la FA, en especial en sus formas paroxísticas; para ello, es necesario un manejo multidisciplinario que integre las modificaciones en el estilo de vida, el manejo de los factores de riesgo y el control de la comorbilidad en el tratamiento de la FA en conjunto con el control del ritmo o de la frecuencia y la anticoagulación. Por desgracia, en la práctica clínica estas estrategias a menudo no se tienen en cuenta, son infrautilizadas y poco estudiadas. Los objetivos del presente posicionamiento son: 1) revisar la relación de los factores de riesgo y la comorbilidad con la FA, 2) revisar los mecanismos fisiopatológicos de cada una de estas condiciones, 3) revisar el impacto del control de los factores de riesgo y de la comorbilidad en el control y en el impacto de la FA, y 4) proporcionar guías y recomendaciones para la puesta en práctica de programas de tratamiento multidisciplinario e integral en pacientes con FA.

Nordihydroguaiaretic Acid Affects Undifferentiated and Differentiated Neuroblastoma Cells Differently through Mechanisms that Impact on Cell Viability.

AIM: We aimed to investigate the mechanisms involved in the neurotoxic effects of NDGA on differentiated and undifferentiated human neuroblastoma cells (MSN), assessing cell viability, changes in the actin cytoskeleton, cell migration and the expression of the 5-LOX enzyme and the inhibitor of cell cycle progression p21WAF1/CIP1. BACKGROUND: High expression and activity of the lipoxygenase enzyme (LOX) have been detected in several tumors, including neuroblastoma samples, suggesting the use of LOX inhibitors as potential therapy molecules. Among these, the natural compound nordihydroguaiaretic acid (NDGA) has been extensively tested as an antiproliferative drug against diverse types of cancer cells. OBJECTIVE: In this study, we analyzed the toxic effect of NDGA on neuroblastoma cells at a dose that did not affect cell survival when they differentiated to a neuron-like phenotype and the potential mechanisms involved in the anticancer properties. METHODS: We exposed human neuroblastoma cells (MSN) to different concentrations of NDGA before and after a differentiation protocol with retinoic acid and nerve growth factor and analyzed cell viability, cell migration, actin cytoskeleton morphology and the levels of the cell cycle inhibitor p21WAF1/CIP1 and 5-LOX. RESULTS: We found that differentiated human neuroblastoma cells are more resistant to NDGA than undifferentiated cells. The toxic effects of NDGA were accompanied by reduced cell migration, changes in actin cytoskeleton morphology, induction of p21WAF1/CIP1 and decreased levels of the 5-LOX enzyme. CONCLUSION: This study provides new evidence regarding the potential use of NDGA to induce cell death in human neuroblastoma.

Gallbladder Cancer Risk and Indigenous South American Mapuche Ancestry: Instrumental Variable Analysis Using Ancestry-Informative Markers.

A strong association between the proportion of indigenous South American Mapuche ancestry and the risk of gallbladder cancer (GBC) has been reported in observational studies. Chileans show the highest incidence of GBC worldwide, and the Mapuche are the largest indigenous people in Chile. We set out to assess the confounding-free effect of the individual proportion of Mapuche ancestry on GBC risk and to investigate the mediating effects of gallstone disease and body mass index (BMI) on this association. Genetic markers of Mapuche ancestry were selected based on the informativeness for assignment measure, and then used as instrumental variables in two-sample Mendelian randomization analyses and complementary sensitivity analyses. Results suggested a putatively causal effect of Mapuche ancestry on GBC risk (inverse variance-weighted (IVW) risk increase of 0.8% per 1% increase in Mapuche ancestry proportion, 95% CI 0.4% to 1.2%, p = 6.7 × 10-5) and also on gallstone disease (3.6% IVW risk increase, 95% CI 3.1% to 4.0%), pointing to a mediating effect of gallstones on the association between Mapuche ancestry and GBC. In contrast, the proportion of Mapuche ancestry showed a negative effect on BMI (IVW estimate -0.006 kg/m2, 95% CI -0.009 to -0.003). The results presented here may have significant implications for GBC prevention and are important for future admixture mapping studies. Given that the association between the individual proportion of Mapuche ancestry and GBC risk previously noted in observational studies appears to be free of confounding, primary and secondary prevention strategies that consider genetic ancestry could be particularly efficient.

Development and internal validation of a multifactorial risk prediction model for gallbladder cancer in a high-incidence country.

Since 2006, Chile has been implementing a gallbladder cancer (GBC) prevention program based on prophylactic cholecystectomy for gallstone patients aged 35 to 49 years. The effectiveness of this prevention program has not yet been comprehensively evaluated. We conducted a retrospective study of 473 Chilean GBC patients and 2137 population-based controls to develop and internally validate three GBC risk prediction models. The Baseline Model accounted for gallstones while adjusting for sex and birth year. Enhanced Model I also included the non-genetic risk factors: body mass index, educational level, Mapuche surnames, number of children and family history of GBC. Enhanced Model II further included Mapuche ancestry and the genotype for rs17209837. Multiple Cox regression was applied to assess the predictive performance, quantified by the area under the precision-recall curve (AUC-PRC) and the number of cholecystectomies needed (NCN) to prevent one case of GBC at age 70 years. The AUC-PRC for the Baseline Model (0.44%, 95%CI 0.42-0.46) increased by 0.22 (95%CI 0.15-0.29) when non-genetic factors were included, and by 0.25 (95%CI 0.20-0.30) when incorporating non-genetic and genetic factors. The overall NCN for Chileans with gallstones (115, 95%CI 104-131) decreased to 92 (95%CI 60-128) for Chileans with a higher risk than the median according to Enhanced Model I, and to 80 (95%CI 59-110) according to Enhanced Model II. In conclusion, age, sex and gallstones are strong risk factors for GBC, but consideration of other non-genetic factors and individual genotype data improves risk prediction and may optimize allocation of financial resources and surgical capacity.

Benchmarks and Geographic Differences in Gallbladder Cancer Surgery: An International Multicenter Study.

BACKGROUND: High-quality surgery plays a central role in the delivery of excellent oncologic care. Benchmark values indicate the best achievable results. We aimed to define benchmark values for gallbladder cancer (GBC) surgery across an international population. PATIENTS AND METHODS: This study included consecutive patients with GBC who underwent curative-intent surgery during 2000-2021 at 13 centers, across seven countries and four continents. Patients operated on at high-volume centers without the need for vascular and/or bile duct reconstruction and without significant comorbidities were chosen as the benchmark group. RESULTS: Of 906 patients who underwent curative-intent GBC surgery during the study period, 245 (27%) were included in the benchmark group. These were predominantly women (n = 174, 71%) and had a median age of 64 years (interquartile range 57-70 years). In the benchmark group, 50 patients (20%) experienced complications within 90 days after surgery, with 20 patients (8%) developing major complications (Clavien-Dindo grade ≥ IIIa). Median length of postoperative hospital stay was 6 days (interquartile range 4-8 days). Benchmark values included ≥ 4 lymph nodes retrieved, estimated intraoperative blood loss ≤ 350 mL, perioperative blood transfusion rate ≤ 13%, operative time ≤ 332 min, length of hospital stay ≤ 8 days, R1 margin rate ≤ 7%, complication rate ≤ 22%, and rate of grade ≥ IIIa complications ≤ 11%. CONCLUSIONS: Surgery for GBC remains associated with significant morbidity. The availability of benchmark values may facilitate comparisons in future analyses among GBC patients, GBC surgical approaches, and centers performing GBC surgery.

Fibrilación auricular en población mexicana: Diferencias en presentación, comorbilidades y factores de riesgo entre hombres y mujeres / Atrial fibrillation in Mexican population: Differences in presentation, comorbidities and risk factors between men and women

Resumen Objetivo: Conocer el comportamiento epidemiológico y asociaciones de la FA en población mexicana. Material y métodos: Analizamos 8,686 pacientes de 38 cardiólogos inscritos en REMECAR, divididos por edad y sexo. Comorbilidades estudiadas: obesidad, ERC, HTA, DM, dislipidemia, EVC, EPOC, hipotiroidismo, IC y CI. Programa: IBM SPSS. Resultados: FA en 498 pacientes (5.7%), mayor prevalencia en hombres (6.1 vs. 5.3%), mayor edad en mujeres (74.3 ± 12.1 vs. 70.5 ± 12.3 años, p < 0.0001). En mujeres menores de 60 años la FA se asoció con IC (p = 0.041), en hombres con ERC (p = 0.43), DM (p = 0.009), EVC (p = 0.001), hipotiroidismo (p = 0.001) e IC (p = 0.001). En mujeres mayores de 60 años se asoció con ERC (p = 0.001), dislipidemia (p = 0.001), EVC (p = 0.001), EPOC (p = 0.001) e IC (p = 0.001), en hombres con ERC (p = 0.002), EVC (p = 0.001), EPOC (p = 0.002), hipotiroidismo (p = 0.002), IC (p = 0.001) y CI (p = 0.033). En mujeres la FA se asoció con 1.13 veces mayor probabilidad de obesidad, 1.13 de HTA, 2.8 de ERC, 2.9 de EPOC, 4.3 de EVC y 6.5 de IC, en hombres la FA se asoció con 1.05 veces mas probabilidad de HTA, 1.4 de DM, 2.1 de ERC, 2.4 de EPOC, 3 de hipotiroidismo, 4.7 de EVC y 6 de IC. Conclusiones: La FA es una arritmia muy frecuente, con mayor prevalencia en pacientes que acuden a consulta de cardiología, en hombres y mayor edad de presentación en las mujeres. A mayor edad, mayor prevalencia de FA y de comorbilidades, la IC es la condición más frecuente con la que se asoció la FA.

Abstract Objective: To know the epidemiological behavior and associations of AF in Mexican population. Material and methods: 8,686 patients from 38 cardiologists participating in REMECAR were analyzed. They were divided by gender and age, the comorbidities studied were obesity, chronic kidney disease (CKD), high blood pressure (HBP), diabetes mellitus (DM), dyslipidemia, stroke, chronic obstructive pulmonary disease (COPD), hypothyroidism, heart failure (HF) and ischemic heart disease (IHD). Program used: IBM SPSS Statistic. Results: AF was diagnosed in 498 patients (5.7%), with higher prevalence in men (6.1% vs. 5.3%) and older age in women (74.3 ± 12.1 vs. 70.5 + -12.3 years, p<0.0001). In those under 60 years, AF was associated in women with HF, in men with CKD, DM, stroke, hypothyroidism and HF. In women older than 60 years, AF was associated with CKD, dyslipidemia, stroke, chronic COPD and HF, in men with CKD, stroke, COPD, hypothyroidism, HF and IHD. AF in women increase the probability 1.13 for obesity, 1.13 for HBP, 2.8 for CKD, 2.9 for COPD, 4.3 for stroke and 6.5 for HF, in men increase the probability 1.05 for HBP, 1.4 for DM, 2.1 for CKD, 2.4 for COPD, 3.0 for hypothyroidism, 4.7 for stroke and 6.0 for HF. Conclusions: AF is a very common arrhythmia, with a higher prevalence in patients attending the cardiology consultation, in men and with an older age of presentation in women. The older the age, the higher the prevalence of AF and comorbidities, HF is the most frequent condition associated with AF.

Kaposi's sarcoma with gastric and rectal involvement in HIV patient.

A 67-year-old man admitted due to dyspnea, violaceous skin lesions and normocytic anemia under study. During admission, the patient is diagnosed with HIV infection in the AIDS phase, in addition to Kaposi's sarcoma with cutaneous, multiple digestive (gastric and rectal) and probably pulmonary involvement. Kaposi's sarcoma is a tumor of vascular origin caused by the human herpes virus type 8. There are four variants, our patient corresponds to the variant related to AIDS. Gastrointestinal involvement presents varied symptoms and the endoscopic image is very characteristic, but as it is a tumor with submucosal involvement, it sometimes requires endoscopic ultrasound-guided biopsy to make the diagnosis. Treatment is based on antiretroviral therapy and systemic chemotherapy.

Identification of Circulating lncRNAs Associated with Gallbladder Cancer Risk by Tissue-Based Preselection, Cis-eQTL Validation, and Analysis of Association with Genotype-Based Expression.

Long noncoding RNAs (lncRNAs) play key roles in cell processes and are good candidates for cancer risk prediction. Few studies have investigated the association between individual genotypes and lncRNA expression. Here we integrate three separate datasets with information on lncRNA expression only, both lncRNA expression and genotype, and genotype information only to identify circulating lncRNAs associated with the risk of gallbladder cancer (GBC) using robust linear and logistic regression techniques. In the first dataset, we preselect lncRNAs based on expression changes along the sequence "gallstones → dysplasia → GBC". In the second dataset, we validate associations between genetic variants and serum expression levels of the preselected lncRNAs (cis-lncRNA-eQTLs) and build lncRNA expression prediction models. In the third dataset, we predict serum lncRNA expression based on individual genotypes and assess the association between genotype-based expression and GBC risk. AC084082.3 and LINC00662 showed increasing expression levels (p-value = 0.009), while C22orf34 expression decreased in the sequence from gallstones to GBC (p-value = 0.04). We identified and validated two cis-LINC00662-eQTLs (r2 = 0.26) and three cis-C22orf34-eQTLs (r2 = 0.24). Only LINC00662 showed a genotyped-based serum expression associated with GBC risk (OR = 1.25 per log2 expression unit, 95% CI 1.04-1.52, p-value = 0.02). Our results suggest that preselection of lncRNAs based on tissue samples and exploitation of cis-lncRNA-eQTLs may facilitate the identification of circulating noncoding RNAs linked to cancer risk.

Somatostatin Therapy Improves Stellate Cell Activation and Early Fibrogenesis in a Preclinical Model of Extended Major Hepatectomy.

Liver resection treats primary and secondary liver tumors, though clinical applicability is limited by the remnant liver mass and quality. Herein, major hepatic resections were performed in pigs to define changes associated with sufficient and insufficient remnants and improve liver-specific outcomes with somatostatin therapy. Three experimental groups were performed: 75% hepatectomy (75H), 90% hepatectomy (90H), and 90% hepatectomy + somatostatin (90H + SST). Animals were followed for 24 h (N = 6) and 5 d (N = 6). After hepatectomy, portal pressure gradient was higher in 90H versus 75H and 90H + SST (8 (3-13) mmHg vs. 4 (2-6) mmHg and 4 (2-6) mmHg, respectively, p < 0.001). After 24 h, changes were observed in 90H associated with stellate cell activation and collapse of sinusoidal lumen. Collagen chain type 1 alpha 1 mRNA expression was higher, extracellular matrix width less, and percentage of collagen-staining areas greater at 24 h in 90H versus 75H and 90H + SST. After 5 d, remnant liver mass was higher in 75H and 90H + SST versus 90H, and Ki-67 immunostaining was higher in 90H + SST versus 75H and 90H. As well, more TUNEL-staining cells were observed in 90H versus 75H and 90H + SST at 5 d. Perioperative somatostatin modified portal pressure, injury, apoptosis, and stellate cell activation, stemming changes related to hepatic fibrogenesis seen in liver remnants not receiving treatment.

Laparoscopic versus open hemihepatectomy: comprehensive comparison of complications and costs at 90 days using a propensity method.

Laparoscopic hemihepatectomy (LHH) may offer advantages over open hemihepatectomy (OHH) in blood loss, recovery, and hospital stay. The aim of this study is to evaluate our recent experience performing hemihepatectomy and compare complications and costs up to 90 days following laparoscopic versus open procedures. Retrospective evaluation of patients undergoing hemihepatectomy at our center 01/2010-12/2018 was performed. Patient, tumor, and surgical characteristics; 90-day complications; and costs were analyzed. Inverse probability of treatment weighting (IPTW) was used to balance covariates. A total of 141 hemihepatectomies were included: 96 OHH and 45 LHH. While operative times were longer for LHH, blood loss and transfusions were less. At 90 days, there were similar rates of liver-specific and surgical complications but fewer medical complications following LHH. Medical complications that arose with greater frequency following OHH were primarily pulmonary complications and urinary and central venous catheter infections. Complications at 90 days were lower following LHH (Clavien-Dindo grade ≥ III OHH 23%, LHH 11%, p = 0.130; Comprehensive Complication Index OHH 20.0 ± 16.1, LHH 10.9 ± 14.2, p = 0.001). While operating costs were higher, costs for hospital stay and readmissions were lower with LHH. Patients undergoing LHH experience a significant reduction in postoperative medical complications and costs, resulting in 90-day cost equity compared with OHH.

Dynamic Angiogenic Switch as Predictor of Response to Chemotherapy-Bevacizumab in Patients With Metastatic Colorectal Cancer.

BACKGROUND: Previous studies have shown that metastatic colorectal carcinoma (mCRC) patients treated with bevacizumab, experience variation in the plasma levels of angiogenesis growth factors and related cytokines, called angiogenic switch (AS). The aim of the present study was to analyze the relationship between AS and the clinical response during standard chemotherapy-bevacizumab treatment. PATIENTS AND METHODS: Patients with Eastern Cooperative Oncology Group 0-1 mCRC were eligible. Patients received treatment with standard dose capecitabine plus either oxaliplatin or irinotecan and bevacizumab for 6 cycles. Initial treatment was followed by maintenance therapy with bevacizumab plus capecitabine until progression. Plasma levels of angiogenic-related cytokines (hepatocyte growth factor, placental growth factor, macrophage chemoattractant protein-3, MM-9, eotaxin, basic fibroblast growth factor, and interleukin 18) were prospectively analyzed at baseline and every 8 weeks. Progression-free survival (PFS) was calculated using the Kaplan-Meier method. RESULTS: A total of 71 patients were enrolled. AS was observed in 45 patients (63.4%), 28 of whom experienced AS at the first evaluation after treatment start. Disease control, which includes partial/complete response and stable disease, was seen in 96% of AS patients (43/45), but only in 15/26 (58%) for the remaining patients without evidence of AS (P<0.001). The median PFS of AS patients was 11.4 months (95% confidence interval, 8.6-15.8) versus 8.3 months for patients without AS (95% confidence interval, 5.6-16.4; P=0.04). CONCLUSIONS: Chemotherapy plus Bevacizumab combination in mCRC patients results in dynamic changes in plasma cytokines, which is associated with better disease control and longer PFS. These new findings support continuing studying AS as a potential marker of angiogenesis inhibitor effectiveness.

Polimorfismo rs17817449 del gen FTO y su influencia en variables antropométricas de jóvenes chilenos / rs17817449 polymorphism of the fto gene and its influence on anthropometric variables of young Chileans

Determinar la distribución genotípica y la frecuencia alélica del polimorfismo rs17817449 del gen FTO en jóvenes chilenos y su influencia en variables antropométricas. Los 96 sujetos jóvenes (18-25 años), 43 hombres y 53 mujeres fueron evaluados utilizando genotipificación del polimorfismo rs17817449 del gen FTO en TT, TG y GG mediante polimerase chain reaction (PCR), además de una evaluación Kinenatropométrica para determinar las variables asociadas a composición corporal. Las variables fueron analizadas estadísticamente según su distribución paramétrica y el nivel de significancia estadística fue p<0,05. La distribución genotípica del polimorfismo rs17817449 de FTO en jóvenes chilenos fue: TT: 50 %; TG: 42,7 %; GG 7,3 % y la distribución alélica fue: T: 0,7105 y G: 0,2895. No se encontraron diferencias estadísticamente significativas en las variables antropométricas al analizar los participantes según modelo de dominancia del alelo G. Se determinó la distribución genotípica y la frecuencia alélica del polimorfismo rs17817449 del gen FTO en jóvenes chilenos, datos desconocidos hasta este momento. De acuerdo a nuestros resultados, no existen diferencias antropométricas entre personas con diferentes genotipos del polimorfismo rs17817449 de FTO, agrupadas según modelo de dominancia del alelo G.

The rs17817449 polymorphism of the FTO gene in young Chileans and their influence on anthropometric variables. 96 young subjects (18-25 years old), 43 men and 53 women were evaluated using genotyping of the rs17817449 polymorphism of the FTO gene in TT, TG and GG by means of polymerase chain reaction (PCR), in addition to a Kinenatropometric evaluation to determine the variables associated with body composition. The variables were analyzed statistically according to their parametric distribution and the level of statistical significance was p<0.05. The genotypic distribution of the FTO polymorphism rs17817449 in young Chileans was: TT: 50 %; TG: 42.7 %; GG 7.3 % and the allelic distribution was: T: 0.7105 and G: 0.2895. No statistically significant differences were found in the anthropometric variables when analyzing the participants according to model of dominance of the G allele. The genotypic distribution and the allelic frequency of the rs17817449 polymorphism of the gene were determined FTO in Chilean population, data unknown until now. According to our results, there are no anthropometric differences between people with different genotypes of the FTO polymorphism rs17817449, nor according to the dominance model of the G.

Distribución geográfica y hábitat de la familia Trochilidae (Aves) en el estado de Guerrero, México / Geographical distribution and habitat of Trochilidae (Aves) in the state of Guerrero, Mexico

ResumenLa distribución y abundancia de la familia Trochillidae generalmente estan influenciadas por la floración y fenología de las plantas de las que se alimentan, principalmente en bosques primarios, por lo que los cambios en la cobertura de la vegetación pueden afectar a sus poblaciones. Se analizó la distribución geográfica y se caracterizó el hábitat para 22 especies residentes de colibríes presentes en el estado de Guerrero con base en el uso de suelo y vegetación de INEGI Serie IV (2007-2010). Los modelos de distribución se generaron con ayuda del Algoritmo Genético para la Producción de Conjuntos de Reglas (GARP), usando los registros históricos de colecciones científicas y trabajo de campo (2001-2009), en combinación con variables climáticas y topográficas. De las 22 especies modeladas, seis son endémicas a México, mismo número de especies que se encuentran en alguna categoría de riesgo. La mayor concentración potencial de la riqueza (14-20 especies), endemismo (5-6 especies) y especies en riesgo de colibríes (5-6 especies) está en la provincia biótica de la Sierra Madre del Sur. No obstante, la distribución potencial de la mayor parte de los colibríes se presenta en ambientes alterados o agroecosistemas resultado de los cambios en el uso del suelo. Solo en el caso de Campylopterus hemileucurus, Lamprolaima rhami y Heliomaster longisrostris, su distribución potencial es mayor en áreas de vegetación primaria. Las áreas de mayor concentración de colibríes no corresponden con las Áreas de Importancia para la Conservación de las Aves en Guerrero, lo que confirma que pese a su diversidad y su extrema popularidad, desde la perspectiva conservacionista los colibríes han recibido relativamente poca atención.

AbstractThe distribution and abundance of species of Trochillidae family is usually influenced by the flowering and phenology of plants used as a feeding source, mainly in primary forest, so that changes in vegetation cover could impact their populations. We analyzed and characterized the geographical distribution and habitat for 22 species of resident hummingbirds in the state of Guerrero using the vegetation and the land use map of INEGI Series IV (2007-2010). Distribution models were generated with the Genetic Algorithm for Rule Set Production (GARP), using historical records of scientific collections and fieldwork (2001-2009), in combination with climatic and topographic variables. Of the 22 modeled species, six are endemic to Mexico, the same number of species found in a risk category. The highest concentration with regards to richness (14-20 species), endemism (5-6 species) and number of threatened species of hummingbirds (5-6 species) occurred in the biotic province of Sierra Madre del Sur. However, the potential distribution of most of the hummingbirds occurred in disturbed sites or agroecosystems, as a result of changes in land-use. For Campylopterus hemileucurus, Lamprolaima rhami and Heliomaster longisrostris, their potential distribution was highest in areas of primary vegetation. Areas of high hummingbirds presence do not coincide with the Important Bird Areas proposed for bird conservation in Guerrero, considering that, despite its diversity and its extreme popularity, from the conservation perspective hummingbirds have received relatively little attention. Rev. Biol. Trop. 64 (1): 363-376. Epub 2016 March 01.