Prevalencia y factores de riesgo de displasia del desarrollo de la cadera en recien nacidos en 2 hospitales sampedranos / Prevalence and risk Factors of hip developmental Dysplasia in newborn in 2 Sampedran Hospitals

la displasia de cadera en desarrollo, es una alteración en el desarrollo y relación anatómica de los componentes de la articulación coxo-femoral que incluye al hueso ilíaco, fémur, cápsula articular, ligamentos y músculos. Puede ser secundaria a causas intrínsecas y/o extrínsecas, que condicionan una relación anormal de la cabeza femoral y el acetábulo. El objetivo: determinar la prevalencia y factores de riesgo de displasia de cadera en desarrollo (DCD) en recién nacidos de Hospitales Mario Catarino Rivas (HMCR) y Leonardo Martínez Valenzuela (HLMV), julio 2018 a junio 2019. Pacientes y métodos: estudio prospectivo, observacional-analítico. Universo; recién nacidos de ambos hospitales. Muestra 167 recién nacidos, muestreo por conveniencia. Se incluyeron neonatos sanos, cuyos padres brindaron su consentimiento informado. Recolección de datos mediante cuestionario tipo encuesta que contenía 22 preguntas cerradas dirigidas a la madre y datos del recién nacido, obtenidos mediante revisión del expediente clínico: maniobras de Barlow y Ortolani, además del estudio de imagen Rayos X AP de cadera mediante el cual se determinó el Índice Acetabular y el Centraje Concéntri- co de Fernández. El análisis de datos se realizó en el programa EPI Info versión 7.2.2.16. Se calculó prevalencia, Riesgo Relativo e Intervalo de Confianza. Tablas y gráficos se realizaron en Microsoft Excel 2017. Resultados: se diagnosticó DCD en 17 neonatos (prevalencia 10.18%). De los cuales; 13 (76.47%) eran del sexo femenino, 15 (88.24%) tenían maniobras de Ortolani y Barlow negativas y 9 (53%) con DCD bilateral. Los factores de riesgo encontrados, fueron: hijos de madres primigestas RR: 2.61 (IC:0.96;7.08), de 24 años o menos RR:3.58 (IC:0.85;15.12), con oligohidramnios RR:2.55 (IC:0.44;14.8). En cuanto a los RN; sexo femenino RR 3.37 (IC:1.15;9.91), presentación pélvica RR 4.9 (IC2.02;11.62), y con antecedentes familiares de DCD: RR 2.55 (IC:0.44;14.80). El embarazo múltiple, resulto ser un factor protector RR 0.00 (IC:0.07;0.75). Conclusión: la DCD se presentó aproximadamente en uno de cada diez recién nacidos. Entre los principales factores de riesgo se encontraron: hijos de madres primigestas, de 24 años o menos con oligohidramnios, además; recién nacidos del sexo femenino, presentación pélvica, y con antecedentes familiares de DCD. El embarazo múltiple resultó ser un factor protector...(AU)

Antitumor Effect of Epigallocatechin Gallate and Vincristine in Mice with L5178Y Lymphoma.

The main objective of research into new therapies is the search for more efficacy and fewer toxic effects in cancer treatments. On one hand, vincristine (VCR) is a chemotherapeutic used in different kinds of tumors. On the other hand, epigallocatechin gallate (EGCG) is a green tea metabolite that has shown an antineoplastic effect in diverse investigations, so the objective of this work is to evaluate the antitumor effects of the EGCG/VCR combination on tumor volume and survival. To achieve this objective, the solid model of lymphoma L5178Y was used in BALB/c mice with different doses of VCR, EGCG, and their combination allowed tumor growth and survival time recording. After tumor collection, measurements, and immunohistochemistry for p53, Bcl2, and Cyclin D1 were performed. The results showed that the EGCG/vincristine combination had a greater antitumor effect than those effects of vincristine and EGCG. It can be attributed to the fact that the greatest inhibition of Bcl2 was present in gathering of EGCG harvest with vincristine. Therefore, the combination of EGCG with vincristine has a better antineoplastic effect by inhibiting tumor development and increasing survival on both substances independently.

The importance of CXCR4 expression in tumor stroma as a potential biomarker in pancreatic cancer.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the main causes of cancer mortality in the world. A characteristic feature of this cancer is that a large part of the tumor volume is composed of a stroma with different cells and factors. Among these, we can highlight the cytokines, which perform their function through binding to their receptors. Given the impact of the CXCR4 receptor in the interactions between tumor cells and their microenvironment and its involvement in important signaling pathways in cancer, it is proposed as a very promising prognostic biomarker and as a goal for new targeted therapies. Numerous studies analyze the expression of CXCR4 but we suggest focusing on the expression of CXCR4 in the stroma. METHODS: Expression of CXCR4 in specimens from 33 patients with PDAC was evaluated by immunohistochemistry techniques and matched with clinicopathological parameters, overall and disease-free survival rates. RESULTS: The percentage of stroma was lower in non-tumor tissue (32.4 ± 5.2) than in tumor pancreatic tissue (67.4 ± 4.8), P-value = 0.001. The level of CXCR4 expression in stromal cells was diminished in non-tumor tissue (8.7 ± 4.6) and higher in tumor pancreatic tissue (23.5 ± 6.1), P-value = 0.022. No significant differences were identified in total cell count and inflammatory cells between non-tumor tissue and pancreatic tumor tissue. No association was observed between CXCR4 expression and any of the clinical or pathological data, overall and disease-free survival rates. Analyzing exclusively the stroma of tumor samples, the CXCR4 expression was associated with tumor differentiation, P-value = 0.05. CONCLUSIONS: In this study, we reflect the importance of CXCR4 expression in the stroma of patients diagnosed with PDAC. Our results revealed a high CXCR4 expression in the tumor stroma, which is related to a poor tumor differentiation. On the contrary, we could not find an association between CXCR4 expression and survival and the rest of the clinicopathological variables. Focusing the study on the CXCR4 expression in the tumor stroma could generate more robust results. Therefore, we consider it key to develop more studies to enlighten the role of this receptor in PDAC and its implication as a possible biomarker.

Eosinophilic gastrointestinal diseases with esophageal involvement: Analysis of 212 patients.

BACKGROUND: Primary eosinophilic gastrointestinal diseases (EGID) are chronic inflammatory disorders of the gastrointestinal tract with unknown etiology. Features, utility, and evolution are still unknown in screening for EGID in adult patients with eosinophilic esophagitis (EoE). OBJECTIVES: To evaluate the prevalence, characteristics, comorbidities, and evolution of EGID in adults diagnosed with EoE and investigate differences between both groups. METHODS: Prospective unicenter observational and analytical study. Gastric and duodenal biopsies were obtained during upper baseline endoscopy in all consecutive EoE adult patients evaluated. A colonoscopy with colon biopsies was performed upon persistent diarrhea and normal duodenal biopsies. RESULTS: 212 EoE patients were included. Nine patients (4.3%) also showed significant eosinophilic infiltration in at least one organ within the digestive tract. The most common site affected was the small bowel (78%). Gastrointestinal symptoms (43% vs. 100%, p<0.002) and, more specifically, either abdominal pain or diarrhea (17% vs. 78%, p<0.001), some food sensitizations, and digestive comorbidities (p<0.05) were significantly more common in patients with EGID. Gastrointestinal symptoms were present in 94/212 (44%) patients, of whom 9 (10%) had EGID. Considering only abdominal pain or diarrhea, 20% suffered from it. CONCLUSIONS: EGID rarely coexist with EoE, even when gastrointestinal symptoms are present. These findings advise against routine gastric, duodenal, or colon biopsies in adult EoE patients with gastrointestinal symptoms. Most of the characteristics of EoE do not change due to having EGID except gastrointestinal symptoms, digestive comorbidities, and sensitizations to some foods. The evolution was generally favorable despite intermittent adherence to treatment, especially maintenance.

Panel de expertos para la elaboración de un modelo de consentimiento informado de obtención y uso de material audiovisual clínico / Proposal of an informed consent form to obtain audiovisual material from patients

BACKGROUND: An informed consent is mandatory to obtain any clinical audiovisual material from patients. Although there are some documents created for this purpose, there are some barriers for their application, such as the context in which they were created, the language and download availability. AIM: To create a proposal for an informed consent form (ICF) for the capture and different uses for audiovisual material from patients. MATERIAL AND METHODS: A bibliographic search was carried out to obtain different ICFs in Spanish and English, which were subjected to a process of translation, counter-translation and fragmentation. Subsequently, a panel of experts was formed by members of the Chilean Society of Plastic Surgery with extensive experience in social networks. Delphi methodology was applied to reach a consensus about the definitive content of the ICF based on the previously selected fragments. RESULTS: ICFs available for download were identified. The panel was made up of seven Plastic Surgeons and two Delphi rounds were carried out through electronic surveys. At the end of the process, an ICF proposal was obtained for therapeutic, academic or scientific purposes and another for dissemination or education in the mass media. CONCLUSIONS: The proposed ICFs were liberated for their use among health care professionals in Chile, who could use them, provided that they are approved by the local healthcare ethics committees.

Fertility sparing treatment in patients with endometrial cancer (FERT-ENC): a multicentric retrospective study from the Spanish Investigational Network Gynecologic Oncology Group (SPAIN-GOG).

OBJECTIVE: The primary objective was to evaluate the response rate of conservative treatment for endometrial cancer, and the secondary objective was to assess oncological, fertility and obstetric outcomes in patients who underwent fertility preservation treatment. MATERIAL AND METHODS: This multicentre, observational, retrospective study evaluated endometrial cancer patients who underwent fertility-sparing treatment in Spanish centres between January 2010 and January 2020. Seventy-three patients with stage IA endometrioid adenocarcinoma of the uterus were included in the study. RESULTS: The levonorgestrel intrauterine device (LNG-IUD) was the most common fertility-sparing treatment (53.4%), followed by megestrol acetate (20.5%) and medroxyprogesterone acetate (16.4%). During the 24-month follow-up period, the rate of complete response to fertility-sparing management was 74% (n = 54), and 8.2% (n = 6) of patients presented a partial response. Additionally, 13 (17.8%) patients presented with persistent disease and six (8.2%) relapsed after response. The LNG-IUD was associated with a higher complete response rate than the other methods (87.2 vs. 58.8%; p = 0.01). Surgical treatment (at least hysterectomy) was performed in 44 (60.3%) patients as the end of fertility-sparing treatment. Four (5.5%) patients presented relapse after surgery, associated with final FIGO stage III (p = 0.036), myometrial invasion > 50% (p = 0.018) and final tumour grade 2-3 (p = 0.018). The mean follow-up period was 57.8 (range 6-159) months. The 5-year relapse-free survival and overall survival rates were 92.6% [95% CI (81.3, 97.2)] and 93.5% [95% CI (80.7, 97.9)], respectively. During follow-up, three patients (4.1%) died of the disease after completion of surgical treatment. Up to 50.7% of patients included in the study attempted to get pregnant. Of these, the rate of pregnancy was 81.1% (n = 30/37), and reproductive techniques were used for this purpose in 78.4% of cases. CONCLUSIONS: Fertility-sparing management presented a high response rate in patients with endometrial cancer. LNG-IUD was associated with a better response rate compared to the other treatment options. Moreover, in patients using this management method, pregnancy could be achieved using reproductive techniques.

[Proposal of an informed consent form to obtain audiovisual material from patients]. / Panel de expertos para la elaboración de un modelo de consentimiento informado de obtención y uso de material audiovisual clínico.

BACKGROUND: An informed consent is mandatory to obtain any clinical audiovisual material from patients. Although there are some documents created for this purpose, there are some barriers for their application, such as the context in which they were created, the language and download availability. AIM: To create a proposal for an informed consent form (ICF) for the capture and different uses for audiovisual material from patients. MATERIAL AND METHODS: A bibliographic search was carried out to obtain different ICFs in Spanish and English, which were subjected to a process of translation, counter-translation and fragmentation. Subsequently, a panel of experts was formed by members of the Chilean Society of Plastic Surgery with extensive experience in social networks. Delphi methodology was applied to reach a consensus about the definitive content of the ICF based on the previously selected fragments. RESULTS: ICFs available for download were identified. The panel was made up of seven Plastic Surgeons and two Delphi rounds were carried out through electronic surveys. At the end of the process, an ICF proposal was obtained for therapeutic, academic or scientific purposes and another for dissemination or education in the mass media. CONCLUSIONS: The proposed ICFs were liberated for their use among health care professionals in Chile, who could use them, provided that they are approved by the local healthcare ethics committees.

Characterization of Permeability Barrier Dysfunction in a Murine Model of Cutaneous Field Cancerization Following Chronic UV-B Irradiation: Implications for the Pathogenesis of Skin Cancer.

Chronic ultraviolet B (UV-B) irradiation is known to be one of the most important hazards acting on the skin and poses a risk of developing photoaging, skin with cutaneous field cancerization (CFC), actinic keratosis (AKs), and squamous cell carcinomas (SCCs). Most of the UV-B light is absorbed in the epidermis, affecting the outermost cell layers, the stratum corneum, and the stratum granulosum, which protects against this radiation and tries to maintain the permeability barrier. In the present work, we show an impairment in the transepidermal water loss, stratum corneum hydration, and surface pH after chronic UV-B light exposure in an immunologically intact mouse model (SKH1 aged mice) of skin with CFC. Macroscopic lesions of AKs and SCCs may develop synchronically or over time on the same cutaneous surface due to both the presence of subclinical AKs and in situ SCC, but also the accumulation of different mutations in keratinocytes. Focusing on skin with CFC, yet without the pathological criteria of AKs or SCC, the presence of p53 immunopositive patches (PIPs) within the epidermis is associated with these UV-B-induced mutations. Reactive epidermis to chronic UV-B exposure correlated with a marked hyperkeratotic hyperplasia, hypergranulosis, and induction of keratinocyte hyperproliferation, while expressing an upregulation of filaggrin, loricrin, and involucrin immunostaining. However, incidental AKs and in situ SCC might show neither hypergranulosis nor upregulation of differentiation markers in the upper epidermis. Despite the overexpression of filaggrin, loricrin, involucrin, lipid enzymes, and ATP-binding cassette subfamily A member 12 (ABCA12) after chronic UV-B irradiation, the permeability barrier, stratum corneum hydration, and surface pH were severely compromised in the skin with CFC. We interpret these results as an attempt to restore the permeability barrier homeostasis by the reactive epidermis, which fails due to ultrastructural losses in stratum corneum integrity, higher pH on skin surface, abundant mast cells in the dermis, and the common presence of incidental AKs and in situ SCC. As far as we know, this is the first time that the permeability barrier has been studied in the skin with CFC in a murine model of SCC induced after chronic UV-B irradiation at high doses. The impairment in the permeability barrier and the consequent keratinocyte hyperproliferation in the skin of CFC might play a role in the physiopathology of AKs and SCCs.

Influence of biomedical education on health and eating habits of university students in Spain.

OBJECTIVE: The aim of this study was to explore the influence of an enrolled degree course on health and eating habits in a population of Spanish university students (17-26 y of age). METHODS: A cross-sectional observational study was carried out with 648 students. Volunteers were stratified into biomedical (medicine and nursing, 48%) and non-biomedical students (other fields of study, 52%). Data were collected using previously self-reported questionnaires focused on anthropometric and sociodemographic profile, lifestyle practices, body image perception, health consciousness, eating habits, physical activity, and food addiction. Mann-Whitney U tests and Pearson's χ2 tests were applied to identify associations between the two groups. RESULTS: Self-reported body mass index was higher for the non-biomedical group (22.1 ± 3.1 versus 23 ± 5 kg/m2; P < 0.05), which also reported less regularity in taking meals (91 versus 95%; P < 0.05), eating fewer colored vegetables and fruits (65 versus 77%; P < 0.001) and a higher alcohol intake (27 versus 20%; P < 0.001). In contrast, the proportion of students that showed more interest in the diet-health duality (92 versus 85%; P < 0.001) and a desire to adopt healthier habits (80 versus 78%; P < 0.05) was larger in the biomedical group. Dietary habits, obtained by means of a food frequency questionnaire, suggested that biomedical students make healthier food choices. Additionally, the group of biomedical students took more walks per week (5.8 ± 1.8 versus 5.5 ± 1.9; P < 0.05). CONCLUSIONS: Healthier lifestyle factors cluster into the biomedical group in various components of the study, except food addiction where no differences were observed. The data presented here suggest the necessity to develop health promotion strategies targeting university students.

Histamine H3 receptor gene variants associated with drug abuse in patients with cocaine use disorder.

BACKGROUND: Preclinical work revealed significant interactions between ligands of the histamine H3 receptor and different drugs of abuse. In the case of psychostimulants, the results reported are somewhat controversial and human data are still scarce, despite the fact that an inverse agonist of the H3 receptor (pitolisant) has reached the market after approval for the treatment of narcolepsy. AIMS: We have studied associations between histamine H3 receptor gene variants and cocaine use disorder to increase the knowledge of the possible involvement of histamine H3 receptor in drug abuse. METHODS: Seven single nucleotide polymorphisms of the histamine H3 receptor gene were genotyped by using a multiplexing assay in 248 samples of subjects with cocaine use disorder and 500 randomized samples of subjects representative of the Spanish population. RESULTS: The study of the epidemiological information associated to the samples revealed that subjects with cocaine use disorder broadly abused alcohol, tobacco and cannabinoids. Two single nucleotide polymorphisms (rs3787430 and rs74627870) were found significantly associated with the occurrence of addiction and one more (rs13042865) was specifically related to the severity of cocaine dependence within drug abusers. CONCLUSIONS: The associations found in this study further extend the hypothesis that histamine H3 receptor function could be relevant in drug abuse in general and cocaine addiction in particular.

Microsurgical Strategies for Prophylaxis of Cancer-Related Extremity Lymphedema: A Comprehensive Review of the Literature.

BACKGROUND: Cancer-related lymphedema represents the first cause of noninfectious secondary extremity lymphedema. This entity is a progressive and debilitating disease with no curative treatment available. With the advent of lymphedema microsurgery, focus has turned into risk reduction and prevention of the disease progression. METHODS: Literature review was conducted to clarify current microsurgical approach to prophylaxis of cancer treatment-related extremity lymphedema. RESULTS: Prophylactic approach could be classified into primary and secondary prevention; microsurgical procedures were performed simultaneously with cancer ablation in primary prevention, and secondary prevention was performed secondarily after cancer treatment for selected high-risk subclinical cases. Indocyanine green lymphography was the most useful method for lymphedema screening after cancer treatment and to diagnose subclinical lymphedema. Several lymphovenous shunt operations were performed as prophylactic procedures, and classified into microsurgical lymphovenous implantation and supermicrosurgical lymphovenous intima-to-intima coaptation. Both showed clinically significant prophylactic effects. CONCLUSION: This review provides a comprehensive overview of the literature regarding microsurgical interventions for the prevention of cancer-related extremity lymphedema. There are several methods for lymphedema prophylaxis and further studies are required to clarify indication of each method.

Capacidad funcional, densidad mineral ósea y marcadores de neoformación-reabsorción ósea en pacientes menores de 18 años con movilidad reducida / Functional capacity, bone mineral density and neoformation-resorption bone markers in patients under 18 years of age with reduced mobility

Resumen: Introducción: La inmovilización prolongada asociada a diversas enfermedades neurológicas, causa osteoporosis secundaria con fracturas patológicas y dolor óseo persistente. Objetivos: Establecer la asociación entre densidad mineral ósea (DMO), marcadores de neoformación y reabsorción ósea y grado de capacidad funcional en pacientes menores de 18 años con movilidad reducida. Pacientes y Método: Estudio transversal, realizado entre 1/1/2016 y 31/12/2017 en pacientes de 6 a 18 años diagnosticados de distintas enfermedades neurológicas en Ciudad Real (España). Se analizaron las variables biodemográficas, capacidad funcional según la Functional Mobility Scale (FMS), que valora la movilidad en 5, 50 y 500 metros, DMO, 25-hidroxi-vitamina D, fosfatasa alcalina, osteocalcina en sangre y telopéptido amino terminal de cadena cruzada de colágeno tipo I en orina (NTX-I). Se expresan DMO, fosfatasa alcalina, osteocalcina y NTX-I en Z score según valores de referencia para edad y sexo. Se utilizaron estadísticas descriptivas y correlaciones de Pearson y Spearman. Resulta dos: 36 pacientes (52,7% niñas), edad media de 8,6 ± 4,7 años. Valor medio de FMS: 5,3 sobre 18. DMO media: -1,99 ± 1,7 desviaciones estándar (DE), fosfatasa alcalina media: -2,64 ± 1,08, osteocalcina media: -2,15 ± 1,39, y NTX-I medio: +3 ± 1,72. Hubo asociación significativa entre DMO y FMS para 5 metros (r = 0,395; p = 0,017) y para la puntuación total (r = 0,365; p = 0,029). No se encon traron diferencias significativas según estadios de desarrollo puberal. Conclusiones: En la población estudiada se observa disminución en la DMO y en marcadores de neoformación ósea y elevación de marcadores de reabsorción ósea sin asociación con el desarrollo puberal. Los pacientes con menor grado de movilidad presentan una DMO inferior.

Abstract: Introduction: Prolonged immobilization associated with several neurological disorders causes se condary osteoporosis with pathological fractures and persistent bone pain. Objectives: To establish the association between bone mineral density (BMD), neoformation and bone resorption markers and the degree of functional capacity in children under 18 years of age with reduced mobility. Pa tients and Method: Cross-sectional study conducted in Ciudad Real, Spain between January 1, 2016, and December 31, 2017 with patients aged between 6 and 18 years diagnosed with different neurological disorders. The following variables were analyzed: age, sex, pubertal stage, functional capacity according to the Functional Mobility Scale (FMS), which assesses the ability to walk from 5, 50 to 500 meters, BMD, 25-hydroxy-vitamin D, alkaline phosphatase and osteocalcin in blood, and N-terminal telopeptide crosslinks in collagen type I (NTX-I) in urine. BMD, alkaline phosphatase, osteocalcin, and NTX-I values are expressed in Z score according to reference values for age and sex. The Pear son and Spearman correlations were used for data analysis. Results: 36 patients (52.7% girls) with an average age of 8.6±4.7 years. Mean FMS value: 5.3 out of 18. Mean BMD: -1.99 ± 1.7 standard deviations (SD), mean alkaline phosphatase: -2.64 ± 1.08, mean osteocalcin: -2.15 ± 1.39, and mean NTX-I: +3 ± 1.72. There was a significant association between BMD and FMS for 5 meters (r = 0.395; p = 0.017) and for total score (r = 0.365; p = 0.029). There were no significant differences according to the stages of pubertal development. Conclusions: In this population, there was a decrease in BMD and bone neoformation markers, and an increase of bone resorption markers with no association with pubertal development. Patients with a lower degree of mobility present a lower BMD.

Preoperative evaluation by functional magnetic resonance imaging in patients with dysembryoplastic neuroepithelial tumours: A case series. / Evaluación prequirúrgica mediante resonancia magnética funcional en pacientes con tumores neuroepiteliales disembrioplásicos: una serie de casos.

INTRODUCTION: Dysembryoplastic neuroepithelial tumours (DNET) are a type of benign glioneuronal neoplasia of typically temporal location that produce drug-resistant epileptic seizures in children and young adults. OBJECTIVE: This work aims to assess the usefulness of functional magnetic resonance imaging (fMRI) in the preoperative study in four patients with DNET. A Philips Intera 3.0 Tesla magnetic resonance imaging scanner and the Blood-Oxygen-Level-Dependent (BOLD) technique were used to obtain the images, making it possible to locate the eloquent areas for language and motor areas through the application of specific paradigms. RESULTS: In one case the tumour was adjacent to Broca's area, in two cases it coincided with Wernicke's area, in one patient it was<1cm from the motor area for the hand and in another close to memory. Only two of the patients were operated on, without postoperative functional deficit. Hemispheric activation contralateral to the tumour suggestive of neuroplasticity was observed in one of the patients. CONCLUSIONS: fMRI is a non-invasive method that allows us to assess the proximity of lesions to eloquent areas, which is key in the evaluation of surgical risk. In addition, it allowed the detection of probable neuroplasticity in one case, which guaranteed the success of the surgery.

The Neuroendocrine and Metabolic Outcomes of Bariatric Surgery Depend on Presurgical Control over Eating.

BACKGROUND: The outcomes of bariatric surgery are very irregular and mostly unpredictable. The search for variables of predictive value is encouraged to help preventing therapeutic failures. OBJECTIVE: We aimed to confirm the hypothesis that preexisting eating behaviors could predict neuroendocrine and metabolic outcomes of gastric bypass surgery in morbidly obese subjects. METHODS: Twenty-one morbidly obese patients from the Bariatric Surgery Program of our hospital were selected according to the specific inclusion and exclusion criteria for this study. The subjects filled out a validated questionnaire to quantify the "loss-of-control" (LC) dimension of food craving and provided serum samples at the onset of the study and 1 year after gastric bypass surgery. Hematological, metabolic, and hormonal variables were studied by conventional clinical tests and enzyme immunoassays and checked for correlations with LC both before and after surgery. RESULTS: Those patients that had exhibited worse eating control at the beginning of the study experienced a better metabolic response 1 year after surgery in terms of reduction of serum insulin, HOMA1-IR, HOMA2-IR, and vitamin D1; all these variables were inversely correlated with presurgical LC. Serum brain-derived neurotrophic factor (BDNF) levels showed the same tendency; in fact, BDNF significantly decreased only in those patients with worse eating control. CONCLUSIONS: Problematic eating behaviors may predict a better response of insulin resistance and a specific reduction of serum BDNF in morbidly obese patients after gastric bypass surgery.

A Step-by-Step Approach to a Successful Cosmetic Breast Reduction.

Evolution of breast reduction techniques has been a result of combining different skin marking patterns with a wide variety of pedicles. Despite the many differences that may exist among these procedures, they all rely on a few key principles. To make surgery more expeditious and minimize technical challenges, these principles can be incorporated into simple surgical strategies. The authors present a step-by-step approach to help to achieve a successful cosmetic breast reduction for patients with small to moderate breast hypertrophy. Special emphasis is given to intraoperative clues that make this procedure more reproducible and straightforward.

Laparoscopic Sleeve Gastrectomy for High-Risk Patients in a Monocentric Series: Long-Term Outcomes and Predictors of Success.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has gained popularity as a stand-alone bariatric procedure, but only a few reports provide data of long-term outcomes on high-risk patients. OBJECTIVE: To evaluate long-term efficacy of LSG as a definitive management on high-risk obese patients and to study factors that predict its success. SETTING: University hospital in Spain. METHODS: A retrospective analysis of prospectively collected data from 134 high-risk patients undergoing LSG from January 2007 through December 2016. Long-term weight loss, resolution of comorbidities, morbidity, and mortality were analyzed. RESULTS: One hundred thirty-four high-risk patients underwent LSG. The mean overall follow-up time was 70.9 ± 4.5 months. The mean age was 47 ± 11.0 years. The mean preoperative body mass index (BMI) was 55.9 ± 6.7 kg/m2 (83.5% were super-obese and 24.6% had BMI ≥ 60). The incidence of postoperative complications was 15%. Mean percentage of total weight loss (%TWL) at 5, 6, 7, and 8 years was 30.7 ± 12.8%, 28.7 ± 14.0%, 29.7 ± 12.3%, and 27.9 ± 11.1%, respectively. Differences were found in age, preoperative BMI, time to reach nadir weight and percentage of excess weight loss (%EWL) at 1 year between patients considered a failure compared to those considered a success. Using multivariate regression analysis, only age (p = 0.009) and time to reach nadir weight after surgery (p = 0.008) correlated with %EWL at 4 years. Resolution of type 2 diabetes (T2DM) was achieved in 62.2% of patients. CONCLUSION: This study supports effectiveness and durability of LSG as a definitive bariatric procedure in high-risk patients.

Prospective Biomarker Study in Advanced RAS Wild-Type Colorectal Cancer: POSIBA Trial (GEMCAD 10-02).

BACKGROUND: RAS testing is used to select patients with anti-epidermal growth factor receptor (EGFR) therapies sensitivity in metastatic colorectal cancer (mCRC). However, other biomarkers such as BRAF, PIK3CA/PTEN, and p-IGF-1R+/MMP7+ (double positive [DP] phenotype) have not been prospectively assessed to predict anti-EGFR resistance. MATERIALS AND METHODS: We designed a multicenter prospective trial (NCT01276379) to evaluate whether the biomarkers BRAF mutation, PIK3CA mutation/PTEN loss, and DP phenotype can improve the prediction for 12-months progression-free survival (PFS) over the use of clinical variables exclusively in patients with RAS wild-type (WT) mCRC treated with standard chemotherapy plus biweekly cetuximab as first-line therapy. The planned sample size was 170 RAS WT patients to detect a 20% difference in 12-month PFS based on the analysis of clinical and selected biomarkers (α = .05, ß = .2). The discriminatory capacity of the biomarkers was evaluated using receiver operating characteristic curves. RESULTS: We included 181 RAS WT patients. The biomarker distribution was as follows: BRAF mutant, 20 patients (11%); PIK3CA mutated/PTEN loss, 98 patients (58%); DP, 23 patients (12.7%). The clinical variables in the clinical score were progression status >0, left-sided tumor, and resectable liver metastasis as the only metastatic site. The area under the curve (AUC) of the score containing the clinical variables was 0.67 (95% confidence interval [CI], 0.60-0.75). The AUC of the score with clinical variables and BRAF mutational status was 0.68 (0.61-0.75, p = .37). The AUC of the score with clinical variables and PI3KCA mutation/PTEN status was 0.69 (0.61-0.76, p = .32). The AUC of the score with clinical variables and DP phenotype was 0.66 (0.58-0.73, p = .09). CONCLUSION: The addition of BRAF, PIK3CA/PTEN, and DP to a clinical score does not improve the discrimination of 12-month PFS. IMPLICATIONS FOR PRACTICE: This prospective biomarker design study has important clinical implications because many prospective clinical trials are designed with the hypothesis that BRAF mutation per se and MEK and PIK3CA downstream pathways are critical for colorectal tumor survival. The results lead to the question of whether these pathways should be considered as passengers instead of drivers.

Short and long-term outcomes of underwater EMR compared to the traditional procedure in the real clinical practice.

BACKGROUND AND AIMS: underwater endoscopic mucosal resection (U-EMR) has been recently described as an alternative to endoscopic mucosal resection (EMR) for flat colorectal polyps. However, the real applications remain unclear due to the lack of comparative studies. METHODS: a multi-centric prospective study was performed from November 2016 to December 2017. All lesions larger than 15 mm that were resected with both techniques were included in the study. The samples were matched using the size, morphology, site and access (SMSA) score as a reference. The efficacy, efficiency and adverse events rates were compared. RESULTS: a total of 162 resections were collected (112 EMR and 50 U-EMR) with an average size of 25 mm. U-EMR achieved better results for the en bloc resection rate (49 vs 62%; p = 0.08) and there were no cases of an incomplete resection (10.7 vs 0%; p = 0.01). U-EMR was faster than EMR and there were no differences in the adverse events rate. Furthermore, U-EMR tended to achieve better results in terms of recurrence. Performing the resection in emersion appeared to prevent the cautery artefact, especially in sessile serrated adenomas. CONCLUSION: in the real clinical practice, U-EMR and EMR are equivalent in terms of efficacy and safety. Furthermore, U-EMR may be a feasible approach to prevent cautery artefact, allowing an accurate pathologic assessment.

Clinical Impact of Circulating Tumor RAS and BRAF Mutation Dynamics in Patients With Metastatic Colorectal Cancer Treated With First-Line Chemotherapy Plus Anti-Epidermal Growth Factor Receptor Therapy.

PURPOSE: RAS and BRAF mutations can be detected as a mechanism of acquired resistance in circulating tumor (ct) DNA in patients with metastatic colorectal cancer treated with anti-epidermal growth factor receptor therapy. METHODS: RAS and BRAF mutational status was assessed in ctDNA in a baseline plasma sample and a serum sample collected at the time of the last available determination (named secondary extraction) from patients with KRAS exon 2 wild-type metastatic colorectal cancer treated in two first-line prospective biomarker-designed clinical trials (PULSE, ClinicalTrials.gov identifier: NCT01288339; and POSIBA, ClincialTrials.gov identifier: NCT01276379). RESULTS: Analysis of extended RAS and BRAF in tissue and plasma from 178 patients with KRAS exon 2 wild-type metastatic colorectal cancer showed a sensitivity of 64.1% and a specificity of 90%. The median overall survival (OS) of baseline patients with RAS and BRAF mutations in ctDNA was 22.3 months (95% CI, 15.6 to 29 months) and 8.9 months (95% CI, 6.3 to 11.4 months), respectively, which was significantly inferior to the median OS of 40.4 months (95% CI, 35.9 to 44.9 months) in two patients with wild-type disease (P < .001). Acquisition of RAS/BRAF mutations occurred in nine of 63 patients (14%) with progressive disease (PD; ie, blood draw within 1 month before PD or after PD) compared with six of 73 patients (8%) with no PD or blood extraction for ctDNA analysis before 1 month of PD (P = .47). Median OS in patients with RAS/BRAF acquisition was 23.9 months (95% CI, 19.7 to 27.9 months) compared with 40.6 months (95% CI, not reached to not reached) in patients who remained free of mutations (P = .016). CONCLUSION: Our results confirm that baseline RAS and BRAF testing in ctDNA discriminates survival. The emergence of RAS/BRAF mutations has limited relevance for the time to progression to anti-epidermal growth factor receptor therapy.