Determining factors of pulse oximetry accuracy: a literature review.

OBJECTIVE: Identify and reach consensus on the variables that affect the measurement of oxygen saturation using pulse oximetry. METHODS: We applied inclusion and exclusion criteria to select relevant studies in databases such as Ebsco and PubMed. The search strategies, carried out until December 2023, focused on publications that addressed the technology of pulse oximeters and variables that influence their accuracy. We assessed the risk of bias of the included studies and used standardized methods for synthesis of results. RESULTS: 23 studies were included. The synthesis of the results highlighted that equipment with tetrapolar technology showed greater precision in oxygen saturation measurements. Increased skin pigmentation, hemoglobinopathies and high skin temperatures can lead to an overestimation of SpO2, while factors such as low perfusion, cold skin temperature, nail polish or tattoos, hypoxemia, anemia and high altitude training, they may underestimate it. On the other hand, motion artifacts, light pollution, frequency >150 beats per minute, electromagnetic interference and location of the sensor can cause distortion of the photoplethymography signal. CONCLUSIONS: The synthesis of the results highlighted that skin pigmentation and light interference can lead to an overestimation of SpO2, while other factors such as low perfusion and altitude tend to underestimate it. The studies presented variability and heterogeneity in their designs, evidencing limitations in the consistency and precision of the evidence. Despite these limitations, the results underscore the importance of considering multiple variables when interpreting pulse oximetry measurements to ensure their reliability. The findings have significant implications for clinical practice and future research.

Experiencia de un hospital monográfico pediátrico y estrategias adoptadas para los cuidados perioperatorios durante la epidemia por SARS-CoV-2 y la reorganización de la atención pediátrica urgente en la Comunidad de Madrid. España / Experience of a pediatric monographic hospital and strategies adopted for perioperative care during the SARS-CoV-2 epidemic and the reorganization of urgent pediatric care in the Community of Madrid. Spain

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PainAPPle. Validación y evaluación de una aplicación electrónica para el manejo del dolor agudo en pacientes pediátricos / PainAPPle. Validation and evaluation of an electronic application for the management of acute pain in pediatric patients

INTRODUCCIÓN: La versión digital de las escalas de valoración recomendadas para el paciente pediátrico podría contribuir a su mejora y a implementar los indicadores de calidad descritos para el manejo del dolor agudo. MATERIAL Y MÉTODOS: Desarrollo de una aplicación electrónica (PainAPPle) que incorpora versiones de las escalas de valoración del dolor y efectos secundarios validados para cada edad, así como las estrategias terapéuticas aceptadas para el manejo del dolor agudo en pacientes pediátricos. Validación psicométrica (validez y fiabilidad) de las escalas incorporadas en 44 pacientes de 4 a 18 años de la unidad de dolor agudo, aplicándoles ambos formatos (papel y electrónico) de todas las escalas en dos mediciones con 30 min de diferencia. Evaluación de los datos recogidos por PainAPPle en pacientes pediátricos a cargo de dicha unidad. RESULTADOS: La fiabilidad se estudió analizando la correlación (Spearman mayor de 0,5, p < 0,001) que obtuvimos para las distintas escalas en dos momentos con 30 min de diferencia, en los mismos pacientes. Para la validez se analizó la correlación (Spearman mayor de 0,5, p < 0,001) entre los valores de las escalas en papel (regla de oro) y en PainAPPle tanto en el minuto 0 como en el minuto 30. Los niveles de concordancia obtenidos teniendo en cuenta el punto de corte de las escalas que obligaría a un tratamiento fueron también estadísticamente significativos (p < 0,005). CONCLUSIONES: PainAPPle es un instrumento validado para el manejo del dolor agudo en pacientes pediátricos. Los datos recogidos permiten aplicar los indicadores de calidad descritos para el manejo del dolor agudo postoperatorio

INTRODUCTION: The digital version of the assessment scales recommended for the pediatric patient could contribute to its improvement and to implement the quality indicators described for the management of acute pain. MATERIAL AND METHODS: Psychometric validation (validity and reliability) of pain assessment and treatment side effects scales incorporated in the electronic application PainAPPle. For this, both formats (paper and electronic) of all the scales were applied in two measurements with 30 minutes of difference in 44 patients from 4 to 18 years of the Acute Pain Unit in the immediate postoperative period. In addition, the data collected by PainAPPle was evaluated by retrospectively applying the quality indicators described for the management of acute postoperative pain. RESULTS: Reliability was studied analyzing the high correlation (Spearman greater than 0.5, P<.001) that we obtained for the values of each scale in two moments with 30minutes of difference, in the same patients. For validity, the high correlation (Spearman greater than 0.5, P<.001) between the values of the paper scales (gold rule) and PainAPPle at both minute 0 and 30 was analyzed. Concordance obtained taking into account the cut-off point of the scales that would force a treatment were also statistically significant (P<.005). CONCLUSIONS: PainAPPle is a validated instrument for the management of acute pain in pediatric patients. The collected data allow to apply the quality indicators described for the management of acute postoperative pain

Manejo anestésico para la resección de masa mediastínica anterior (MMA) en paciente pediátrico. Descripción de un caso clínico / Anesthetic management during anterior mediastinal mass resection in a pediatric patient. A case report

Las complicaciones inducidas por anestesia general (AG) y relajación neuromuscular (RNM) en cirugía de masa mediastínica anterior pueden ser graves, sobre todo si existe clínica de compresión de la vía aérea o grandes vasos, como disnea u ortopnean entre otros. Es preferible realizar el procedimiento en ventilación espontánea para evitar el colapso respiratorio o cardiovascular por decúbito supino o por pérdida de la presión negativa intratorácica con la AG y RNM. En caso de precisar decúbito supino y RNM se realizarán paso a paso con técnicas de rescate preparadas (posición de rescate, broncoscopio, esternotomía). Una correcta evaluación preoperatoria, adecuada planificación y abordaje multidisciplinar permiten realizar una anestesia y cirugía seguras. Presentamos el caso de un niño con antecedentes de ortopnea severa con diagnóstico de masa mediastínica anterior, linfoma linfoblástico (parada respiratoria y colapso cardiovascular en sedación para punción lumbar y biopsia de médula ósea) que no responde al tratamiento médico y precisa cirugía de resección bajo AG con RNM

Complications induced by general anesthesia (GA) and neuromuscular relaxation (NMR) in anterior mediastinal mass (AMM) resection can be serious, especially when there are signs of compression of the airway or large vessels (dyspnea, orthopnea, etc.) (1). It is preferable to perform the procedure in spontaneous ventilation to avoid respiratory or cardiovascular collapse due to the supine position or to loss of negative intrathoracic pressure with GA and NMR. If the supine position and NMR are unavoidable, procedures should be performed in a step-wise manner, and rescue strategies should be prepared (rescue position, bronchoscope, sternotomy). Correct preoperative evaluation, adequate planning, and a multidisciplinary approach will ensure patient safety. We present the case of a child with a history of severe orthopnea and a diagnosis of AMM and lymphoblastic lymphoma (respiratory arrest and cardiovascular collapse during sedation for lumbar puncture and bone marrow biopsy) that did not respond to medical treatment and required resection surgery under GA with NMR

Painapple®. Validation and evaluation of an electronic application for the management of acute pain in pediatric patients. / PainAPPle. Validación y evaluación de una aplicación electrónica para el manejo del dolor agudo en pacientes pediátricos.

INTRODUCTION: The digital version of the assessment scales recommended for the pediatric patient could contribute to its improvement and to implement the quality indicators described for the management of acute pain. MATERIAL AND METHODS: Psychometric validation (validity and reliability) of pain assessment and treatment side effects scales incorporated in the electronic application PainAPPle. For this, both formats (paper and electronic) of all the scales were applied in two measurements with 30minutes of difference in 44 patients from 4 to 18years of the Acute Pain Unit in the immediate postoperative period. In addition, the data collected by PainAPPle was evaluated by retrospectively applying the quality indicators described for the management of acute postoperative pain. RESULTS: Reliability was studied analyzing the high correlation (Spearman greater than 0.5, P<.001) that we obtained for the values of each scale in two moments with 30minutes of difference, in the same patients. For validity, the high correlation (Spearman greater than 0.5, P<.001) between the values of the paper scales (gold rule) and PainAPPle at both minute 0 and 30 was analyzed. Concordance obtained taking into account the cut-off point of the scales that would force a treatment were also statistically significant (P<.005). CONCLUSIONS: PainAPPle is a validated instrument for the management of acute pain in pediatric patients. The collected data allow to apply the quality indicators described for the management of acute postoperative pain.

Anesthetic management during anterior mediastinal mass resection in a pediatric patient. A case report. / Manejo anestésico para la resección de masa mediastínica anterior (MMA) en paciente pediátrico. Descripción de un caso clínico.

Complications induced by general anesthesia (GA) and neuromuscular relaxation (NMR) in anterior mediastinal mass (AMM) resection can be serious, especially when there are signs of compression of the airway or large vessels (dyspnea, orthopnea, etc.) (1). It is preferable to perform the procedure in spontaneous ventilation to avoid respiratory or cardiovascular collapse due to the supine position or to loss of negative intrathoracic pressure with GA and NMR. If the supine position and NMR are unavoidable, procedures should be performed in a step-wise manner, and rescue strategies should be prepared (rescue position, bronchoscope, sternotomy). Correct preoperative evaluation, adequate planning, and a multidisciplinary approach will ensure patient safety. We present the case of a child with a history of severe orthopnea and a diagnosis of AMM and lymphoblastic lymphoma (respiratory arrest and cardiovascular collapse during sedation for lumbar puncture and bone marrow biopsy) that did not respond to medical treatment and required resection surgery under GA with NMR.

Color tunable pressure sensors based on polymer nanostructured membranes for optofluidic applications.

We demonstrate an integrated optical pressure sensing platform for multiplexed optofluidics applications. The sensing platform consists in an array of elastomeric on-side nanostructured membranes -effectively 2D photonic crystal- which present colour shifts in response to mechanical stress that alter their nanostructure characteristical dimensions, pitch or orientation. The photonic membranes are prepared by a simple and cost-effective method based on the infiltration of a 2D colloidal photonic crystal (CPC) with PDMS and their integration with a microfluidic system. We explore the changes in the white light diffraction produced by the nanostructured membranes when varying the pneumatic pressure in the microfluidics channels as a way to achieve a power-free array of pressure sensors that change their reflective colour depending on the bending produced on each sensor. The structural characterization of these membranes was performed by SEM, while the optical properties and the pressure-colour relation were evaluated via UV-Vis reflection spectrometry. Maximum sensitivities of 0.17 kPa-1 is obtained when measuring at Littrow configuration (θin = -θout), and close to the border of the membranes. The reflected colour change with pressure is as well monitorized by using a smartphone camera.

La tomografía computarizada corporal como factor asociado a menor mortalidad en el traumatismo geriátrico grave con afectación toracoabdominopélvica / Whole-body computed tomography as a factor associated with lower mortality in severe geriatric trauma with thoracic-abdominal-pelvic injury

Objetivo: Analizar la asociación de la realización de una tomografía computarizada (TC) corporal con la mortalidad intrahospitalaria en pacientes de edad avanzada con afectación toracoabdominopélvica que precisa ingreso en una unidad de cuidados intensivos. Pacientes y método: Estudio observacional, descriptivo y retrospectivo realizado sobre 140 pacientes con edad igual o mayor de 65 años ingresados en una unidad de cuidados intensivos tras un traumatismo con afectación toracoabdominopélvica. Se establecen 2 grupos, según se haya realizado TC corporal como parte rutinaria del estudio o el diagnóstico se estableciera mediante radiografía convencional o ecografía. Análisis comparativo de ambos grupos y análisis de la mortalidad mediante regresión logística. Resultados: La edad media fue de 75,16±8,89 años. La puntuación media en la escala APACHE II fue de 16,25±8,4 puntos, y en la escala Injury Severity Score, de 22,38±15,45 puntos. Se realizó TC corporal en 102 pacientes (72,9%). En estos se observó una menor mortalidad (15,7 frente a 52,6%; p¿0,001), una menor necesidad de ventilación mecánica (47,1 frente a 65,8%; p=0,049) y una menor puntuación en la escala APACHE II (14,75±7,19 frente a 20,26±10,06 puntos; p=0,003). El análisis multivariante mostró una menor mortalidad en los pacientes en los que se realizó TC corporal, con una OR de 0,21 (IC 95% 0,07-0,68; p=0,010), tras ajustar por puntuación en la escala APACHE II y en el Injury Severity Score. Conclusiones: La realización de TC corporal como parte del estudio del traumatismo podría mejorar el manejo de los pacientes de edad avanzada con afectación toracoabdominopélvica que ingresan en una unidad de cuidados intensivos

Objective: To determine the relationship between the use of whole-body computed tomography (WB-CT) and hospital mortality in elderly patients with thoracic-abdominal-pelvic injury requiring admission to an intensive care unit. Patients and method: An observational, descriptive and retrospective study was conducted on 140 patients aged 65 years and older admitted to the intensive care unit after a thoracic-abdominal-pelvic injury. Two groups were established, depending on whether a WB-CT was performed as a routine part of the study or the diagnosis was established by conventional radiography or ultrasound. A comparative analysis was performed on both groups, as well as an analysis of mortality through logistic regression. Results: The mean age of the patients was 75.16±8.89 years. The mean score on the APACHE II scale was 16.25±8.4 points, and on the Injury Severity Score scale, 22.38±15.45 points. WB-CT was performed on 102 patients (72.9%). In these patients, there was a lower mortality rate (15.7 vs. 52.6%, P¿.001), a lower need for mechanical ventilation (47.1 vs. 65.8%, P=.049), and a lower score on the APACHE II scale (14.75±7.19 vs. 20.26±10.06 points, P=.003). The multivariate analysis showed a lower mortality in the patients in whom WB-CT was performed, with an OR of 0.21 (95% CI 0.07-0.68; (P=.010), after adjusting for the APACHE II and ISS scores. Conclusions: Performing a WB-CT scan as part of the trauma study could improve the management of elderly patients with thoracic-abdominal-pelvic involvement admitted to the intensive care unit

Behaviour of polysulfone ultrafiltration membrane for dyes removal.

Although ultrafiltration membranes have been used for the separation of macromolecules and colloids from solutions, this process has a limited application in the removal of dyes present in coloured discharges of textile industry, as these typically have much lower molecular weight than the molecular cut-off of the membranes (MWCO). In the present work, we have evaluated the behaviour of a polysulfone ultrafiltration membrane in the removal of different dyes from aqueous solutions (Congo red, methyl green and amaranth). Different variables (tangential flow rate, concentration of dye and pH of the feed) were studied to determine their influence on the separation processes (permeate flux and rejection coefficient). The results show that Congo red is easily removed with a GR60PP membrane (MWCO = 25 kDa), whereas methyl green and amaranth show rejection coefficient values of approximately 25.78% and 13.85%, respectively, at neutral pH. Also, an interesting effect is observed for the rejection coefficient for methyl green at different pH values. In addition, several treatments were performed to the membrane so as to modify its surface, trying to improve the values obtained for permeate flux and rejection rate.

Whole-body computed tomography as a factor associated with lower mortality in severe geriatric trauma with thoracic-abdominal-pelvic injury. / La tomografía computarizada corporal como factor asociado a menor mortalidad en el traumatismo geriátrico grave con afectación toracoabdominopélvica.

OBJECTIVE: To determine the relationship between the use of whole-body computed tomography (WB-CT) and hospital mortality in elderly patients with thoracic-abdominal-pelvic injury requiring admission to an intensive care unit. PATIENTS AND METHOD: An observational, descriptive and retrospective study was conducted on 140 patients aged 65 years and older admitted to the intensive care unit after a thoracic-abdominal-pelvic injury. Two groups were established, depending on whether a WB-CT was performed as a routine part of the study or the diagnosis was established by conventional radiography or ultrasound. A comparative analysis was performed on both groups, as well as an analysis of mortality through logistic regression. RESULTS: The mean age of the patients was 75.16±8.89 years. The mean score on the APACHE II scale was 16.25±8.4 points, and on the Injury Severity Score scale, 22.38±15.45 points. WB-CT was performed on 102 patients (72.9%). In these patients, there was a lower mortality rate (15.7 vs. 52.6%, P˂.001), a lower need for mechanical ventilation (47.1 vs. 65.8%, P=.049), and a lower score on the APACHE II scale (14.75±7.19 vs. 20.26±10.06 points, P=.003). The multivariate analysis showed a lower mortality in the patients in whom WB-CT was performed, with an OR of 0.21 (95% CI 0.07-0.68; (P=.010), after adjusting for the APACHE II and ISS scores. CONCLUSIONS: Performing a WB-CT scan as part of the trauma study could improve the management of elderly patients with thoracic-abdominal-pelvic involvement admitted to the intensive care unit.

Dynamic soluble changes in sVEGFR1, HGF, and VEGF promote chemotherapy and bevacizumab resistance: A prospective translational study in the BECOX (GEMCAD 09-01) trial.

Despite initial responsiveness, acquired resistance to both bevacizumab and chemotherapy in metastatic colorectal cancer is universal. We have recently published that in vitro, chronically oxaliplatin resistance upregulates soluble vascular endothelial growth factor receptor 1, downregulates vascular endothelial growth factor, and also promotes c-MET, b-catenin/transcription factor 4, and AKT activation. We tested whether variation in three serum biomarkers such as the natural c-MET ligand (hepatocyte growth factor), soluble vascular endothelial growth factor receptor 1, and vascular endothelial growth factor-A was associated with efficacy in metastatic colorectal cancer patients treated in the prospective BECOX study. Serum levels of vascular endothelial growth factor-A165, soluble vascular endothelial growth factor receptor 1, and hepatocyte growth factor were assessed by enzyme-linked immunosorbent assay method basally and every 3 cycles (at the time of computed tomography evaluation) in a preplanned translational study in the first-line BECOX trial in metastatic colorectal cancer patients treated with CAPOX plus bevacizumab. Response was evaluated by routine contrast-enhanced computed tomography by RECIST 1.1 by investigator assessment and by three blinded independent radiologists. Ratios between soluble vascular endothelial growth factor receptor 1/vascular endothelial growth factor-A and hepatocyte growth factor/vascular endothelial growth factor-A were established and variations through time were related to RECIST 1.1 by investigator assessment and independent radiologist. The BECOX trial included 68 patients, and 27 patients were analyzed in the translational trial. A total of 80 RECIST 1.1 evaluations were done by investigator assessment and 56 by independent radiologist. We found that a 3.22-fold increase in soluble vascular endothelial growth factor receptor 1/vascular endothelial growth factor-A by investigator assessment and a 3.06-fold increase in soluble vascular endothelial growth factor receptor 1/vascular endothelial growth factor-A by independent radiologist from previous determination were associated with responses compared with 1.38-fold increase by investigator assessment and 1.59 by independent radiologist in non-responders (p = 0.0009 and p = 0.03, respectively). Responders had a 3.36-fold increase in hepatocyte growth factor/vascular endothelial growth factor-A from previous determination by investigator assessment and 3.66-fold increase in hepatocyte growth factor/vascular endothelial growth factor-A by independent radiologist compared with 1.43-fold increase by investigator assessment and 1.53 by independent radiologist for non-responders (p = 0.002 and 0.003, respectively). In conclusion, a decrease in vascular endothelial growth factor-A and an increase in soluble vascular endothelial growth factor receptor 1 during chemotherapy and bevacizumab exposure can contribute to both chemotherapy (due to c-MET/b-catenin activation) and bevacizumab (due to low vascular endothelial growth factor requirements) resistance. Because hepatocyte growth factor levels decrease also during acquired resistance, alternative strategies to hepatocyte growth factor-ligand inhibition should be investigated.

Successful desensitization to irinotecan after severe hypersensitivity reaction

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El ratón deficiente en apolipoproteína E, un modelo traslacional para el estudio de la aterosclerosis / Apolipoprotein E–deficient mouse, a translational model for the study of atherosclerosi

INTRODUCCIÓN: La aterosclerosis es una de las principales causas de morbimortalidad en países desarrollados que presenta varias similitudes histopatológicas con la inflamación crónica. Los ratones deficientes en apolipoproteína E (apoE-/−) son ampliamente utilizados en el estudio de los mecanismos implicados en el inicio y el progreso de las lesiones ateroscleróticas. OBJETIVO: Evaluar el impacto en la formación de la placa de ateroma de una dieta aterogénica en el ratón apoE-/−. MATERIAL Y MÉTODOS: Ratones apoE-/− de 2 meses de edad fueron sometidos o no a una dieta hipercolesterolémica (10,8% de grasa, 0,75% en colesterol) durante 2 meses adicionales. Se determinó el perfil lipídico, la lesión y el contenido en macrófagos, linfocitos, colágeno, células de la musculatura lisa vascular (CMLV) y core necrótico por técnicas histológicas e inmunohistoquímicas. Cuantificación de las interacciones leucocito-endotelio por microscopia intravital en la microcirculación cremastérica. RESULTADOS: Los ratones apoE-/− sometidos a dieta hipercolesterolémica mostraron elevados niveles circulantes de colesterol total y triglicéridos frente aquellos sometidos a dieta control. Estos efectos fueron acompañados de un claro desarrollo de lesión aterosclerótica en la aorta caracterizada por un mayor contenido en macrófagos (Mac3+), linfocitos (CD3+), colágeno, core necrótico y CMLV. Paralelamente hubo una mayor adhesividad de los leucocitos al endotelio arteriolar en aquellos animales sometidos a dieta grasa. CONCLUSIÓN: El modelo de aterosclerosis que se desarrolla en el ratón apoE-/− sometido a dieta aterogénica presenta numerosas similitudes con la lesión humana, y constituye un adecuado modelo para la detección de nuevas dianas terapéuticas y ensayo de nuevos fármacos

INTRODUCTION: Atherosclerosis is one of the leading causes of morbidity and mortality in Western countries and bears several histopathological similarities to chronic inflammation. Mice deficient in apolipoprotein E (apoE-/−) are widely used in the study of the mechanisms involved in the onset and progression of the atherosclerotic lesion. OBJECTIVE: To evaluate the impact of an atherogenic diet in lesion formation in apoE-/− mice. MATERIAL AND METHODS: Two month-old apoE-/− mice were subjected, or not (controls), to a high fat/high cholesterol diet (10.8% fat, .75% cholesterol) for two months. Lipid profile, lesion formation, and macrophage, lymphocyte, collagen, vascular smooth muscle cells (VSMC), and necrotic core content, were determined within the lesion using histological and immunohistochemical techniques. Leukocyte-endothelial cell interactions were quantified by intravital microscopy in the cremaster microcirculation. RESULTS: apoE-/− mice subjected to a hypercholesterolemic diet showed increased circulating levels of total cholesterol and triglycerides compared to those subjected to a control diet. These effects were accompanied by a clear development of atherosclerotic lesion in the aorta, which was characterized by enhanced macrophage (Mac3+), lymphocyte (CD3+) collagen, VSMC and necrotic core content. In parallel, increased adhesiveness of leukocytes to the arteriolar endothelium in those animals subjected to an atherogenic diet was also detected. CONCLUSION: The atherosclerosis model in apoE-/− mice subjected to an atherogenic diet shares common features with the human atherosclerotic lesion, and constitutes an appropriate model to detect new therapeutic targets and evaluate novel developed drugs

Pazopanib in pretreated advanced neuroendocrine tumors: a phase II, open-label trial of the Spanish Task Force Group for Neuroendocrine Tumors (GETNE).

BACKGROUND: The management of advanced neuroendocrine tumors (NETs) has recently changed. We assessed the activity of pazopanib after failure of other systemic treatments in advanced NETs. METHODS: This was a multicenter, open-label, phase II study evaluating pazopanib as a single agent in advanced NETs (PAZONET study). The clinical benefit rate (CBR) at 6 months was the primary end point. Translational correlation of radiological response and progression-free survival (PFS) with circulating and tissue biomarkers was also evaluated. RESULTS: A total of 44 patients were enrolled. Twenty-five patients (59.5%) were progression-free at 6 months (4 partial responses, 21 stable diseases) with a median PFS of 9.5 months [95% confidence interval (CI) 4.8-14.1]. The CBR varied according to prior therapy received, with 73%, 60% and 25% in patients treated with prior multitarget inhibitors, prior mTOR inhibitors and both agents, respectively. A nonsignificant increase in PFS was observed in patients presenting lower baseline circulating tumor cell (CTC) counts (9.1 versus 5.8 months; P = 0.22) and in those with decreased levels of soluble-vascular endothelial growth factor receptor-2 (sVEGFR-2) (12.6 versus 9.1 months; P = 0.067). A trend toward reduced survival was documented in patients with VEGFR3 rs307821 and rs307826 missense polymorphisms [hazard ratio (HR): 12.3; 95% CI 1.09-139.2; P = 0.042 and HR: 6.9; 95% CI 0.96-49.9; P = 0.055, respectively]. CONCLUSIONS: Pazopanib showed clinical activity in patients with advanced NETs regardless of previous treatments. Additionally, CTCs, soluble-s VEFGR-2 and VEGFR3 gene polymorphisms constitute potential biomarkers for selecting patients for pazopanib (NCT01280201). CLINICAL TRIAL NUMBER: NCT01280201.

Chemoradiation, surgery and adjuvant chemotherapy versus induction chemotherapy followed by chemoradiation and surgery: long-term results of the Spanish GCR-3 phase II randomized trial†.

BACKGROUND: The primary results of our phase II randomized trial suggested that compared with conventional preoperative chemoradiation (CRT), the addition of chemotherapy (CT) before CRT and surgery allows most patients receive their planned treatment with a better toxicity profile without compromising the pathological complete response and complete resection rates. We now report the 5-year outcomes. PATIENTS AND METHODS: Patients with distal or middle third, T3-T4 and/or N+ rectal adenocarcinoma selected by magnetic resonance imaging, were randomly assigned to arm A-preoperative CRT followed by surgery and four cycles of postoperative adjuvant capecitabine and oxaliplatin (CAPOX)-or arm B-four cycles of CAPOX followed by CRT and surgery. The following 5-year actuarial outcomes were assessed: the cumulative incidence of local relapse (LR) and distant metastases (DM), disease-free (DFS) and overall survival (OS). RESULTS: A total of 108 eligible patients were randomly assigned to arm A (n = 52) or arm B (n = 56). With a median follow-up of 69.5 months, 5-year DFS was 64% in arm A and 62% in arm B (P = 0.85) and 5-year OS was 78% in arm A and 75% in arm B (P = 0.64). The 5-year cumulative incidence of LR was 2% and 5% (P = 0.61) and 5-year cumulative incidence of DM was 21% and 23%; (P = 0.79) in arms A and B, respectively. CONCLUSION: Both treatment approaches yield similar outcomes. Given the lower acute toxicity and improved compliance with induction CT compared with adjuvant CT, integrating effective systemic therapy before CRT and surgery is a promising strategy and should be examined in phase III trials.

Combined treatment with bexarotene and rosuvastatin reduces angiotensin-II-induced abdominal aortic aneurysm in apoE(-/-) mice and angiogenesis.

BACKGROUND AND PURPOSE: Abdominal aortic aneurysm (AAA) is a degenerative vascular disease associated with angiogenesis. Bexarotene is a retinoid X receptor (RXR) ligand with anti-angiogenic activity. Statins also exert anti-angiogenic activity and activate PPARs. Because RXR ligands form permissive heterodimers with PPARs and a single anti-angiogenic drug may not be sufficient to combat the wide array of angiogenic factors produced during AAA, we evaluated the effect of combined low doses of bexarotene and rosuvastatin in a mouse model of AAA. EXPERIMENTAL APPROACH: The effect of the combined treatment was investigated in a murine model of angiotensin II-induced AAA in apoE(-/-) mice. This combination therapy was also evaluated in in vivo (Matrigel plug assay) and in vitro (endothelial cell differentiation assay) models of angiogenesis as well as the underlying mechanisms involved. KEY RESULTS: Co-treatment with bexarotene plus rosuvastatin reduced aneurysm formation, inflammation and neovascularization compared with each single treatment. In HUVEC, the combination of suboptimal concentrations of bexarotene and rosuvastatin inhibited angiotensin II-induced morphogenesis, proliferation and migration. These effects were accompanied by diminished production of pro-angiogenic chemokines (CXCL1, CCL2 or CCL5) and VEGF, and seemed to be mediated by RXRα/PPARα and RXRα/PPARγ activation. This combined therapy reduced the activation of members of the downstream PI3K pathway (Akt/mTOR and p70S6K1) in vivo and in vitro. CONCLUSIONS AND IMPLICATIONS: The combination of RXR agonists with statins at low doses synergistically interferes with the signalling pathways that modulate inflammation and angiogenesis and may constitute a new and safer therapeutic treatment for the control of AAA.

Role of circulating tumor cells as prognostic marker in resected stage III colorectal cancer.

BACKGROUND: The prognostic role of circulating tumor cells (CTC) in early colorectal cancer (CRC) has not been determined yet. We evaluated the potential prognostic value of CTC in stage III CRC patients. PATIENTS AND METHODS: Prospective multicenter study of 519 patients with stage III CRC recruited between January 2009 and June 2010. CTC were enumerated with the CellSearch System after primary tumor resection and before the start of adjuvant therapy. A total of 472 patients were included in the analysis. RESULTS: CTC ≥1, ≥2, ≥3 and ≥5 were detected in 166 (35%), 93 (20%), 57 (12%) and 34 (7%) patients, respectively. Median follow-up was 40 months. In the overall population, CTC ≥1 (disease-free survival (DFS): HR 0.97, P = 0.85; overall survival (OS): HR 1.03, P = 0.89), ≥2 (DFS: HR 1.07, P = 0.76; OS: HR 1.02, P = 0.95), ≥3 (DFS: HR 0.96, P = 0.87; OS: HR 0.74, P = 0.41) and ≥5 (DFS: HR 0.72, P = 0.39; OS: HR 0.48, P = 0.21) were not associated with worse DFS and OS. No clinicopathological characteristics were significantly associated with the presence of CTC. In patients with disease relapse, the proportion with CTC ≥1 was not significantly different between those with single versus multiple metastatic locations (37.9% versus 31.4%, P = 0.761). In the multivariate analysis, CTC ≥1 was not an independent prognostic factor for DFS (HR 0.97, P = 0.87) and OS (HR 0.96, P = 0.89). CONCLUSION: CTC detection was not associated with worse DFS and OS in patients with stage III CRC. Given the scarcity of CTC in these patients, it is likely that CTC determined by CellSearch system does not have a prognostic role in this setting. However, a longer follow-up is needed.

First-line bevacizumab and capecitabine-oxaliplatin in elderly patients with mCRC: GEMCAD phase II BECOX study.

BACKGROUND: Subgroup analyses of clinical studies suggest that bevacizumab plus XELOX is effective and tolerable in elderly patients with metastatic colorectal cancer (mCRC). The prospective BECOX study examined the efficacy and safety of bevacizumab plus XELOX, followed by bevacizumab plus capecitabine in elderly patients with mCRC. METHODS: Patients aged ⩾70 years with Eastern Cooperative Oncology Group performance status 0 out of 1 and confirmed mCRC were included. Patients received bevacizumab 7.5 mg kg(-1) and oxaliplatin 130 mg m(-2) on day 1, plus capecitabine 1000 mg m(-2) bid orally on days 1-14 every 21 days; oxaliplatin was discontinued after 6 cycles. The primary end point was time to progression (TTP). RESULTS: The intent-to-treat population comprised 68 patients (65% male, median age 76 years). Median TTP was 11.1 months; median overall survival was 20.4 months; overall response rate was 46%. Grade 3 or 4 adverse events included diarrhoea (18%) and asthenia (16%). Grade 3 or 4 adverse events of special interest for bevacizumab included deep-vein thrombosis (6%) and pulmonary embolism (4%). CONCLUSIONS: Bevacizumab plus XELOX was effective and well tolerated in elderly patients in the BECOX study. The adverse-event profile was similar to previous reports; no new safety concerns were identified. Fit elderly patients with mCRC should be considered for treatment with bevacizumab plus XELOX.