Association of Circulating Tumor Cells and Tumor Molecular Profile With Clinical Outcomes in Patients With Previously Untreated Metastatic Colorectal Cancer: A Pooled Analysis of the Phase III VISNÚ-1 and Phase II VISNÚ-2 Randomized Trials.

BACKGROUND: The bCTC count is a well-established prognostic biomarker in mCRC, as well as in other tumor types. The aim of this analysis was to evaluate the prognostic/predictive role of the bCTC count (≥3 vs. <3) in previously untreated mCRC. PATIENTS AND METHODS: The study involved 589 untreated mCRC patients included in the intention-to-treat population of 2 randomized clinical trials (phase III VISNU-1 [NCT01640405] and phase II VISNU-2 [NCT01640444] studies). RESULTS: Of the 589 patients, 349 (59.2%) had bCTC≥3 and 240 (40.7%) had bCTC<3. Multivariate analysis showed that the bCTC count is an independent prognostic factor for overall survival (OS) (HR 0.59, 95% CI 0.48-0.72; P = 0.000) and potential for progression-free survival (PFS) (P = 0.0549). Median OS was 32.9 and 19.5 months in patients with bCTC<3 and bCTC≥3 (P <0.001), respectively. This effect was also observed comparing OS in RASwt patients from both studies. Other prognostic factors were: ECOG-PS, primary tumor site, number of metastatic sites and surgery of the primary tumor. Median OS was lower for patients treated with anti-VEGF versus anti-EGFR (22.3 vs. 33.3 months, P <0.0001) while there were no significant differences in PFS according to the targeted treatment received. CONCLUSION: This post-hoc analysis of 2 randomized studies confirms the poor prognosis of patients with bCTC≥3 but this is not associated with other adverse independent prognostic factors such as RAS/BRAF mutations.

A signature of circulating microRNAs predicts the response to treatment with FOLFIRI plus aflibercept in metastatic colorectal cancer patients.

The benefit of adding the antiangiogenic drug aflibercept to FOLFIRI regime in metastatic colorectal cancer (CRC) patients resistant to or progressive on an oxaliplatin-based therapy has been previously demonstrated. However, the absence of validated biomarkers to predict greater outcomes is a major challenge encountered when using antiangiogenic therapies. In this study we investigated profiles of circulating microRNAs (miRNAs) to build predictive models of response to treatment and survival. Plasma was obtained from 98 metastatic CRC patients enrolled in a clinical phase II trial before receiving FOLFIRI plus aflibercept treatment, and the circulating levels of 754 individual miRNAs were quantified using real-time PCR. A distinct signature of circulating miRNAs differentiated responder from non-responder patients. Remarkably, most of these miRNAs were found to target genes that are involved in angiogenic processes. Accordingly, some of these miRNAs had predictive value and entered in predictive models of response to therapy, progression of disease, and survival of patients treated with FOLFIRI plus aflibercept. Among these miRNAs, circulating levels of hsa-miR-33b-5p efficiently discriminated between responder and non-responder patients and predicted the risk of disease progression. Moreover, the combination of circulating VEGF-A and miR-33b-5p levels improved clinical stratification of metastatic CRC patients who were to receive FOLFIRI plus aflibercept treatment. In conclusion, our study supports circulating miRNAs as valuable biomarkers for predicting better outcomes in metastatic CRC patients treated with FOLFIRI plus aflibercept.

[Frequency of chest X-ray suggestive of SARS-CoV-2 involvement from March to May 2020 in the population of an urban health area]. / Frecuencia de Rx de tórax indicativas de afectación por SARS-CoV-2 de marzo a mayo de 2020 en la población de un área de salud urbana.

OBJECTIVE: Know the number and percentage of chest X-rays (CXR) referred to a Primary Care Imaging Center and Primary Care Emergency Center to rule out lung involvement due to SARS-CoV-2 from March 16 to May 15, 2020, in an urban health area of about 400,000 reference population inhabitants. To determine the percentage of cases suggestive of pulmonary involvement due to SARS-CoV-2 CXR and the percentage of cases without pulmonary involvement of the total CXR derived in the reference population from March 16 to May 15, 2020. MATERIAL AND METHODS: Design observational descriptive study. The radiological criteria to classify probable pulmonary infection by SARS-CoV-2 (RxT[+]) are: 1) focal opacity; 2) faint focal opacity; 3) faint diffuse increase in density; 4) focal or diffuse interstitial pattern, and 5) focal or diffuse interstitial alveolus pattern. RESULTS AND CONCLUSIONS: Maintain CXR as a useful screening method in the middle stages of the disease, when CXR is more sensitive to detect lung involvement due to SARS-CoV-2. Our graph of affectation by SARS-CoV-2 does not present assessable differences with the expected curve in an epidemic.

Frecuencia de Rx de tórax indicativas de afectación por SARS-CoV-2 de marzo a mayo de 2020 en la población de un área de salud urbana / Frequency of chest X-ray suggestive of SARS-CoV-2 involvement from March to May 2020 in the population of an urban health area

OBJETIVO: Conocer el número y el porcentaje de radiografías de tórax (RxT) derivadas a un centro de diagnóstico por imagen de Atención Primaria y al Centro de Urgencias de Atención Primaria para descartar afectación pulmonar por SARS-CoV-2 desde el 16 de marzo al 15 de mayo de 2020, en un área de salud urbana de unos 400.000 habitantes de población de referencia. Determinar el porcentaje de casos indicativos de afectación pulmonar por RxT por SARS-CoV-2 y el porcentaje de casos sin afectación pulmonar del total de RxT derivadas en la población de referencia desde el 16 de marzo al 15 de mayo de 2020. MATERIAL Y MÉTODOS: Diseño: estudio descriptivo observacional. Los criterios radiológicos para catalogar de probable infección pulmonar por SARS-CoV-2 (RxT[+]) son: 1) opacidad focal; 2) tenue opacidad focal; 3) tenue aumento de densidad difuso; 4) patrón intersticial focal o difuso, y 5) patrón alveolointersticial focal o difuso. RESULTADOS Y CONCLUSIONES: Mantener la RxT como método útil de cribado en las etapas medias de la enfermedad, cuando la RxT es más sensible para detectar afectación pulmonar por SARS-CoV-2. Nuestra gráfica de afectación por SARS-CoV-2 no presenta diferencias valorables con la curva esperada en una epidemia

OBJECTIVE: Know the number and percentage of chest X-rays (CXR) referred to a Primary Care Imaging Center and Primary Care Emergency Center to rule out lung involvement due to SARS-CoV-2 from March 16 to May 15, 2020, in an urban health area of about 400,000 reference population inhabitants. To determine the percentage of cases suggestive of pulmonary involvement due to SARS-CoV-2 CXR and the percentage of cases without pulmonary involvement of the total CXR derived in the reference population from March 16 to May 15, 2020. MATERIAL AND METHODS: Design observational descriptive study. The radiological criteria to classify probable pulmonary infection by SARS-CoV-2 (RxT[+]) are: 1) focal opacity; 2) faint focal opacity; 3) faint diffuse increase in density; 4) focal or diffuse interstitial pattern, and 5) focal or diffuse interstitial alveolus pattern. RESULTS AND CONCLUSIONS: Maintain CXR as a useful screening method in the middle stages of the disease, when CXR is more sensitive to detect lung involvement due to SARS-CoV-2. Our graph of affectation by SARS-CoV-2 does not present assessable differences with the expected curve in an epidemic

Circulating Cell-Free DNA-Based Liquid Biopsy Markers for the Non-Invasive Prognosis and Monitoring of Metastatic Pancreatic Cancer.

Liquid biopsy may assist in the management of cancer patients, which can be particularly applicable in pancreatic ductal adenocarcinoma (PDAC). In this study, we investigated the utility of circulating cell-free DNA (cfDNA)-based markers as prognostic tools in metastatic PDAC. Plasma was obtained from 61 metastatic PDAC patients, and cfDNA levels and fragmentation were determined. BEAMing technique was used for quantitative determination of RAS mutation allele fraction (MAF) in cfDNA. We found that the prognosis was more accurately predicted by RAS mutation detection in plasma than in tissue. RAS mutation status in plasma was a strong independent prognostic factor for both overall survival (OS) and progression-free survival (PFS). Moreover, RAS MAF in cfDNA was also an independent risk factor for poor OS, and was strongly associated with primary tumours in the body/tail of the pancreas and liver metastases. Higher cfDNA levels and fragmentation were also associated with poorer OS and shorter PFS, body/tail tumors, and hepatic metastases, whereas cfDNA fragmentation positively correlated with RAS MAF. Remarkably, the combination of CA19-9 with MAF, cfDNA levels and fragmentation improved the prognostic stratification of patients. Furthermore, dynamics of RAS MAF better correlated with patients' outcome than standard CA19-9 marker. In conclusion, our study supports the use of cfDNA-based liquid biopsy markers as clinical tools for the non-invasive prognosis and monitoring of metastatic PDAC patients.

SEOM clinical guidelines for diagnosis and treatment of metastatic colorectal cancer (2018).

Colorectal cancer (CRC) is the second cause of cancer death in Spain, the objective of this guide published by the Spanish Society of Medical Oncology is to develop a consensus for the diagnosis and management of metastatic disease. The optimal treatment strategy for patients with metastatic CRC should be discussed in a multidisciplinary expert team to select the most appropriate treatment, and integrate systemic treatment and other options such as surgery and ablative techniques depending on the characteristics of the tumour, the patient and the location of the disease and metastases.

Benefits of an automatic patient dose registry system for interventional radiology and cardiology at five hospitals of the Madrid area.

The purpose of this article is to present the results of connecting the interventional radiology and cardiology laboratories of five university hospitals to a unique server using an automatic patient dose registry system (Dose On Line for Interventional Radiology, DOLIR) developed in-house, and to evaluate its feasibility more than a year after its introduction. The system receives and stores demographic and dosimetric parameters included in the MPPS DICOM objects sent by the modalities to a database. A web service provides a graphical interface to analyse the information received. During 2013, the system processed 10 788 procedures (6874 cardiac, 2906 vascular and 1008 neuro interventional). The percentages of patients requiring clinical follow-up due to potential tissue reactions before and after the use of DOLIR are presented. The system allowed users to verify in real-time, if diagnostic (or interventional) reference levels are fulfilled.

Evaluación de los resultados del programa «Parto en el hospital, comadrona en casa» / Evaluation of the results of the program 'Birth in hospital, midwife at home'

OBJETIVO: Describir las características y la evolución clínica de las puérperas y los neonatos incluidos en un programa de alta precoz hospitalaria. MATERIAL Y MÉTODO: Estudio observacional y descriptivo de la población incluida en el programa «Parto en el hospital, comadrona en casa», del Hospital Clínic de Barcelona, desde octubre de 2010 hasta abril de 2013. RESULTADOS: Participaron un total de 150 madres, con una edad (media ± desviación estándar) de 32 ± 4 años. El 70% (n= 105) eran multíparas. Respecto al origen de las participantes, el 57,3% (n= 86) procedían de España, el 24% (n= 36) de Sudamérica y el 13,3% (n= 20) de los países del resto de Europa. Un 95% (n= 137) tenía pareja estable. El 62% (n= 93) tenía estudios superiores. El 55% (n= 82) de los partos fueron con analgesia peridural. El 21% (n= 32) requirió episiotomía o tuvo un desgarro de grado II. El resto no presentó ningún desgarro perineal, o éste fue degrado I. La media de estancia hospitalaria fue de 14 ± 4 horas. El peso de los neonatos al nacer y en el domicilio fue de 3.366 ± 362 y 3.168± 344 g, respectivamente. El 96% (n= 144) de las mujeres eligió lactancia materna al alta. En la visita, el 94% (n= 134) continuaba con lactancia exclusiva y el 7,4% (n= 11) presentaba grietas. El 4% (n= 6) de las mujeres y de los neonatos se visitó en urgencias durante el puerperio, y hubo 2 (1,3%) reingresos neonatales, por crisis cianótica e ictericia, respectivamente. CONCLUSIONES: Las mujeres que participaron en el programa eran principalmente españolas, multíparas y con estudios superiores, y en la mitad de los casos optaron por un parto con analgesia peridural. Las dificultades encontradas a las 24 horas tras el alta estaban relacionadas con la lactancia materna, y fue necesaria la determinación precoz de la bilirrubina. El programa facilita el empoderamiento de las familias, sin incrementar la morbilidad materna o del neonato

OBJECTIVE: To describe the characteristics and clinical course of postpartum women and infants who join a program of early discharge. MATERIAL AND METHOD: An observational, cross-sectional study of the population included in the 'Birth in hospital, midwife at home' program, at the Hospital Clínic of Barcelona, from October 2010 to April2013. RESULTS: 150 mothers were included in the program with a maternalage of 32 ± 4 years. The 70% (n= 105) were multiparous. Place of birth: Spain 57.3% (n= 86), South America 24% (n= 36) and Europe 13.3% (n= 20). 95% (n= 137) were married or living together. 62% (n= 93) attended University. 55% (n= 82) of deliveries were under epidural analgesia.21% (n= 32) of deliveries required episiotomy or had a second degree tear. No perineal tear or first-degree tear was observed in the others. The average length of stay at the hospital after delivery was 14 ±4 hours (x ± SD). The birth weight was 3,366 ± 362 g and the neonatal weight at home was 3,168 ± 344 g. 96% (n= 144) of women chose breastfeeding at discharge. At home, 94% (n= 134) continued exclusive breastfeeding and 7.4% (n= 11) had nipple cracks. 4% (n= 6) of the women and newborn had a consultation in the emergency unit during the postpartum period. There were 2 (1.3%) readmissions to the neonatal intensive care unit because of cyanotic crisis and jaundice. CONCLUSIONS: Women who join the program are mainly Spanish, multiparous and highly educated. Half of them chose to have an epidural. The difficulties at 24 h after discharge are mainly related to breastfeeding. Early determination of bilirubin is necessary. The program facilitates the empowerment of families without increasing maternal or neonatal morbidity

Litiasis y estenosis del colédoco provocada por la migración de un clip quirúrgico / Choledochal lithiasis and stenosis secondary to the migration of a surgical clip

La migración de un clip al colédoco tras una colecistectomía es un hecho infrecuente, habitualmente tardío, que puede ocasionar complicaciones diversas como la formación de litiasis en la vía biliar, o la aparición de obstrucción y estenosis. Presentamos un caso de migración de un clip tras una colecistectomía laparoscópica ocurrido un año tras la intervención, que se presentó clínicamente con un cuadro de colangitis, resuelta mediante la colocación de una endoprótesis biliar mediante de una colangiopancreatografía retrógrada endoscópica (AU)

The migration of a clip to the common bile duct after cholecystectomy is an uncommon, usually late, complication that can lead to diverse complications like stone formation, stenosis, and obstruction in the bile duct. We present the case of a patient who presented with signs and symptoms of cholangitis due to clip migration one year after laparoscopic cholecystectomy; endoscopic retrograde cholangiopancreatography and biliary tract stent placement resolved the problem (AU)

[Choledochal lithiasis and stenosis secondary to the migration of a surgical clip]. / Litiasis y estenosis del colédoco provocada por la migración de un clip quirúrgico.

The migration of a clip to the common bile duct after cholecystectomy is an uncommon, usually late, complication that can lead to diverse complications like stone formation, stenosis, and obstruction in the bile duct. We present the case of a patient who presented with signs and symptoms of cholangitis due to clip migration one year after laparoscopic cholecystectomy; endoscopic retrograde cholangiopancreatography and biliary tract stent placement resolved the problem.

SEOM Clinical guidelines for the treatment of advanced colorectal cancer 2013

Colorectal cancer (CRC) is the most common malignant tumor in Western countries. Despite efforts made to implement screening programmes for early detection and treatment, still half of the patients present or will eventually develop distant metastasis. Management of advanced CRC should be discussed within an experienced multidisciplinary team, to adequately select the most appropriate systemic therapeutic option, as well as the optimal way to integrate it with surgical procedures when indicated. Disease localization and extent, resectability of primary and metastatic disease, tumor biology and dynamics, clinical symptoms, personal preferences and patient's ability to tolerate intensive chemotherapy or extensive surgical procedures are the key factors to properly design a customized treatment plan. The aim of the current manuscript is to provide synthetic practical guidelines regarding therapeutic options for advanced CRC (AU)

SEOM clinical guidelines for the treatment of advanced colorectal cancer 2013.

Colorectal cancer (CRC) is the most common malignant tumor in Western countries. Despite efforts made to implement screening programmes for early detection and treatment, still half of the patients present or will eventually develop distant metastasis. Management of advanced CRC should be discussed within an experienced multidisciplinary team, to adequately select the most appropriate systemic therapeutic option, as well as the optimal way to integrate it with surgical procedures when indicated. Disease localization and extent, resectability of primary and metastatic disease, tumor biology and dynamics, clinical symptoms, personal preferences and patient's ability to tolerate intensive chemotherapy or extensive surgical procedures are the key factors to properly design a customized treatment plan. The aim of the current manuscript is to provide synthetic practical guidelines regarding therapeutic options for advanced CRC.

Human-associated extended-spectrum ß-lactamase in the Antarctic.

Escherichia coli bacteria with extended-spectrum ß-lactamase (ESBL) type CTX-M resistance were isolated from water samples collected close to research stations in Antarctica. The isolates had bla(CTX-M-1) and bla(CTX-M-15) genotypes and sequence types (ST) indicative of a human-associated origin. This is the first record of ESBL-producing enterobacteria from Antarctica.

SEOM clinical guidelines for the treatment of advanced colorectal cancer

Colorectal cancer is the first cause of cancer diagnosis in Spain. Over half of the patients are diagnosed with or will eventually develop distant metastasis. The current manuscript aims to provide synthetic practical guidelines for the therapeutic approaches in advanced disease. Available systemic therapeutic options, and integration and sequencing of chemotherapy with surgical procedures are discussed. Extent of disease, treatment objective, tumor kras mutation status, as well as patient's functional and comorbid conditions shall be considered to properly design the most adequate therapeutic strategy (AU)

SEOM clinical guidelines for the treatment of advanced colorectal cancer.

Colorectal cancer is the first cause of cancer diagnosis in Spain. Over half of the patients are diagnosed with or will eventually develop distant metastasis. The current manuscript aims to provide synthetic practical guidelines for the therapeutic approaches in advanced disease. Available systemic therapeutic options, and integration and sequencing of chemotherapy with surgical procedures are discussed. Extent of disease, treatment objective, tumor kras mutation status, as well as patient's functional and comorbid conditions shall be considered to properly design the most adequate therapeutic strategy.

Effects of optical brighteners used in biopesticide formulations on crops: reflectance, stomatal conductance, photosynthesis, and growth.

Optical brighteners have attracted interest as adjuvant's in baculovirus-based biological insecticides due to their ability enhance the insecticidal properties of these viruses and protect virus particles from the degrading effects of ultraviolet (UV) radiation. The effects of two types of optical brighteners, Tinopal CBS (a distyryl-biphenyl derivative) and Tinopal C1101 (an ethenediyl benzenesulfonic derivative) at 1 or 3% (wt./vol.), on growth of different crOPs [maize, Zea mays L. (var. HY-311), sorghum, Sorghum vulgare Pers. (var. Silo), tomato, Lycopersicum esculentum L. (var. Floradade IT), or pepper, Capsicum annum L. (var. Cal Won 300)] were examined after once a week application during four weeks. Both compounds significantly affected the growth of maize plants, whereas sorghum plants were affected only at the highest concentration of Tinopal C1101. Neither brightener had negative effects on tomato or peppers plants. Both compounds increased the percentage of reflectance of maize and tomato leaves when analyzed using laboratory and field spectrophotometers. A greenhouse experiment involving single application of 1 and 3% Tinopal C1101 indicated that the stomatal conductance and photosynthetic rate of maize and tomato plants were not significantly affected. We conclude that the effects of optical brighteners on plant growth are more likely to be influenced by differences between plant species than differences between brightener compounds.

Application of chemometric studies to metal concentrations in molluscs from the Strait of Magellan (Chile).

Na, K, Ca, Mg, Fe, Cu, Zn, Mn, Se, Ni, and Cd concentrations were determined in 126 mollusc samples belonging to five different species (Mytilus chilensis, n = 47; Nacella deaurata, n = 65; Aulacomya ater, n = 4; Fissurella picta, n = 4; Acanthina monodon, n = 6) collected from the coasts of the Strait of Magellan. The metals analysed presented significant differences between the mean concentrations for the mollusc species considered. Factor and discriminant analyses made possible the differentiation of the mollusc species. In addition, when discriminant analysis was used, good classifications were obtained according to sampling zone and weight-to-length ratio of the organisms.

Sodium, K, Ca, Mg, Fe, Cu, and Zn concentrations in molluscs from the Magellan Strait (Chile): their contribution to dietary intake.

The concentrations of the essential metals Na, K, Ca, Mg, Fe, Cu, and Zn were determined in 126 specimens of molluscs belonging to five different species: Mytilus chilensis, n=47; Nacella deaurata, n=65; Aulacomya ater, n=4; Fissurella picta, n=4; Acanthina monodon, n=6, collected from the coastline of the Magellan Strait. Significant differences were obtained among the mean metal concentrations in the mollusc species considered. The contribution to the dietary daily intake of these metals for the consumption of one serving of these molluscs was high, especially the contribution to the Fe intake for the consumption of N. deaurata. Some significant differences were observed among the mean concentrations for the studied metals according to the zone of sampling. The influence of the zone of sampling on the mean concentration of metals in N. deaurata was higher than in M. chilensis. The application of lineal discriminant analysis (LDA) made it possible to differentiate statistically between specimens according to the mollusc species. Within the each mollusc species, the LDA helped to identify specimens according to the zone of sampling and weight/length ratio.

A 6-month regimen for EPTB with intermittent treatment in the continuation phase: a study of 679 cases.

BACKGROUND: No large studies have demonstrated the effectiveness of a 6-month regimen for all forms of extra-pulmonary tuberculosis (EPTB). METHODS: Retrospective, observational analysis to evaluate the effectiveness of a 6-month treatment regimen (2HRZE/4H3R3) for all patients diagnosed with EPTB in Caracas, Venezuela, from 1 January 1998 to 31 December 2000, using direct observation. RESULTS: Of 679 patients enrolled, 101 (14.9%) had AIDS. In 83.2% the diagnosis was based on microbiological, histological or genetic amplification information. Of 612 (90.1%) patients who took more than 90% of the doses, treatment had to be altered in six (1%) due to drug side effects. Of the remaining 606 patients who took more than 90% of the doses, 603 (99.5%) were cured and three failed. In the follow-up conducted 2 years after the end of treatment, only 6 relapsed (1%). Cures without relapse were achieved in 24 cases of central nervous system involvement, 27 cases of osteoarticular involvement and in the 42 who had miliary and/or disseminated TB. CONCLUSION: A 6-month treatment regimen for all forms of EPTB, with treatment three times a week during the continuation phase, was highly effective.

Manganese, nickel, selenium and cadmium in molluscs from the Magellan Strait, Chile.

The concentrations of manganese, selenium, nickel and cadmium were determined in 112 samples of molluscs belonging to mussels (Mytilus chilensis, n = 47) and limpets (Nacella deaurata, n = 65), which were collected from the coastline of the Magellan Strait, Chile. Four (6.2%) samples of limpets exceeded the maximum limits for cadmium established in Europe. Limpets showed higher mean manganese, nickel and cadmium concentrations than mussels, whilst the mean selenium concentration in mussels was higher. The consumption of one serving (100 g) of molluscs represents a considerable contribution to the dietary daily intake of selenium, and limpets make a significant contribution to the manganese and cadmium intakes. The sampling zone influenced the trace element concentrations, and different uptakes were observed between the mollusc species.