"I heard it before or not": time-course of ERP response and behavioural correlates associated with false recognition memory.

Electrophysiological and behavioural correlates of true and false memories were examined in the Deese/Roediger-McDermont (DRM) paradigm. A mass univariate approach for analysing event-related potentials (ERP) in the temporal domain was used to examine the electrophysiological effects associated with this paradigm precisely (point-by-point) and without bias (data-driven). Behaviourally, true and false recognition did not differ, and the predicted DRM effect was observed, as false recognition of critical lures (i.e., new words semantically related to studied words) was higher than false alarms of new (unrelated) words. Neurally, an expected old/new effect was observed during the time-range of the late positive component (LPC) over left centro-parietal scalp electrodes. Furthermore, true recognition also evoked larger LPC amplitudes than false recognition over both left centro-parietal and fronto-central scalp electrodes. However, we did not observe LPC-related differences between critical lures and new words, nor between correct rejections of critical lures and new words. In contrast, correct rejections of critical lures were accompanied by higher activation of a sustained positive slow wave (SPSW) in right fronto-central electrodes beyond 1200 ms. This result reveals a key role of post-retrieval processes in recognition. Results are discussed in light of theoretical approaches to false memory in the DRM paradigm.

El impacto del TDAH sobre la lectura / The impact of ADHD on reading

Resumen Más allá de la frecuente coexistencia del trastorno por déficit de atención con hiperactividad (TDAH) y el trastorno específico del aprendizaje de la lectura, la presente revisión pretende examinar la evidencia empírica disponible sobre cómo el TDAH impacta negativamente sobre el aprendizaje de la lectura. Los datos existentes apuntan a que la presencia del trastorno (especialmente los síntomas de falta de atención), puede afectar a i) la correcta adquisición de lectura, ya sea de manera directa o a través de su influencia sobre los precursores de la lectura; ii) las propias habilidades de decodificación (precisión y fluidez lectora), tanto de manera directa como indirecta a través de su influencia sobre procesos cognitivos como la distracción o las funciones ejecutivas; y ii) la comprensión lectora, probablemente de manera indirecta por las dificultades eje cutivas y en la memoria de trabajo verbal características del TDAH. Estas conclusiones presentan importantes implicaciones para caracterizar e intervenir mejor sobre las dificultades lectoras en el TDAH, ya sean clínicas o subclínicas.

Abstract Beyond the frequent coexistence of attention deficit hyperactivity disorder (ADHD) and reading dis order (dyslexia), the present review aims to examine the available empirical evidence on how ADHD negatively impacts on learning to read. Existing data suggest that the presence of the disorder (especially inattention symp toms), may affect i) the correct acquisition of reading, either directly or through its influence on the precursors to reading; ii) decoding skills themselves (reading accuracy and fluency), both directly and indirectly through its influence on cognitive processes such as distractibility or executive functions; and iii) reading comprehension, probably indirectly through the executive and verbal memory difficulties characteristic of ADHD. These findings have important implications for better characterizing and intervening on reading difficulties in ADHD, whether clinical or subclinical.

[The impact of ADHD on reading]. / El impacto del TDAH sobre la lectura.

Beyond the frequent coexistence of attention deficit hyperactivity disorder (ADHD) and reading disorder (dyslexia), the present review aims to examine the available empirical evidence on how ADHD negatively impacts on learning to read. Existing data suggest that the presence of the disorder (especially inattention symptoms), may affect i) the correct acquisition of reading, either directly or through its influence on the precursors to reading; ii) decoding skills themselves (reading accuracy and fluency), both directly and indirectly through its influence on cognitive processes such as distractibility or executive functions; and iii) reading comprehension, probably indirectly through the executive and verbal memory difficulties characteristic of ADHD. These findings have important implications for better characterizing and intervening on reading difficulties in ADHD, whether clinical or subclinical.

Más allá de la frecuente coexistencia del trastorno por déficit de atención con hiperactividad (TDAH) y el trastorno específico del aprendizaje de la lectura, la presente revisión pretende examinar la evidencia empírica disponible sobre cómo el TDAH impacta negativamente sobre el aprendizaje de la lectura. Los datos existentes apuntan a que la presencia del trastorno (especialmente los síntomas de falta de atención), puede afectar a i) la correcta adquisición de lectura, ya sea de manera directa o a través de su influencia sobre los precursores de la lectura; ii) las propias habilidades de decodificación (precisión y fluidez lectora), tanto de manera directa como indirecta a través de su influencia sobre procesos cognitivos como la distracción o las funciones ejecutivas; y ii) la comprensión lectora, probablemente de manera indirecta por las dificultades ejecutivas y en la memoria de trabajo verbal características del TDAH. Estas conclusiones presentan importantes implicaciones para caracterizar e intervenir mejor sobre las dificultades lectoras en el TDAH, ya sean clínicas o subclínicas.

Déficits neuropsicológicos, intensidad sintomática y repercusión funcional en el trastorno por déficit de atención con hiperactividad / Neuropsychological deficits, symptom intensity and functional impairment in attention deficit hyperactivity disorder

Resumen Este estudio pretende contribuir a una mejor comprensión del trastorno por déficit de atención con hiperactividad (TDAH) examinado de manera exhaustiva la relación entre dos de los principales déficits cognitivos del trastorno (la atención y el control inhibitorio), la sintomatología (falta de atención e hipe ractividad/impulsividad) y la repercusión funcional en 85 niños/as y adolescentes con TDAH sin otros trastornos comórbidos. Encontramos, con independencia del funcionamiento intelectual general y de la edad, que i) un mayor déficit atencional e inhibitorio, predijo una mayor gravedad de los síntomas del TDAH, ii) un mayor déficit atencional e inhibitorio predijo un mayor deterioro funcional, pero no de una manera directa sino a través de los síntomas, y iii) una mayor severidad sintomática predijo una mayor repercusión funcional. Comenzar a explorar y comprender la complejidad del TDAH es clave para avanzar en nuestro conocimiento del trastorno y para la correcta toma de decisiones clínicas.

Abstract This study aims to contribute to a better understanding of at tention deficit hyperactivity disorder (ADHD) by comprehensively examining the relationship between two of the main cognitive deficits of the disorder (attention and inhibitory control), symptomatology (inattention and hyperactivity/impulsivity) and functional impairment in 85 children and adolescents with ADHD without other comorbid disorders. We found, independent of general intellectual functioning and age, that i) greater atten tional and inhibitory deficits predicted greater severity of ADHD symptoms, ii) greater attentional and inhibitory deficits predicted greater functional impairment, but not in a direct way but through symptoms, and iii) greater symptomatic severity predicted greater functional impairment. Beginning to explore and understand the com plexity of ADHD is key to advance our knowledge of the disorder and for correct clinical decision making.

[Neuropsychological deficit, symptom intensity and functional impairment in attention deficit hyperactivity disorder]. / Déficits neuropsicológicos, intensidad sintomática y repercusión funcional en el trastorno por déficit de atención con hiperactividad.

This study aims to contribute to a better understanding of attention deficit hyperactivity disorder (ADHD) by comprehensively examining the relationship between two of the main cognitive deficits of the disorder (attention and inhibitory control), symptomatology (inattention and hyperactivity/impulsivity) and functional impairment in 85 children and adolescents with ADHD without other comorbid disorders. We found, independent of general intellectual functioning and age, that i) greater attentional and inhibitory deficits predicted greater severity of ADHD symptoms, ii) greater attentional and inhibitory deficits predicted greater functional impairment, but not in a direct way but through symptoms, and iii) greater symptomatic severity predicted greater functional impairment. Beginning to explore and understand the complexity of ADHD is key to advance our knowledge of the disorder and for correct clinical decision making.

Este estudio pretende contribuir a una mejor comprensión del trastorno por déficit de atención con hiperactividad (TDAH) examinado de manera exhaustiva la relación entre dos de los principales déficits cognitivos del trastorno (la atención y el control inhibitorio), la sintomatología (falta de atención e hiperactividad / impulsividad) y la repercusión funcional en 85 niños/as y adolescentes con TDAH sin otros trastornos comórbidos. Encontramos, con independencia del funcionamiento intelectual general y de la edad, que i) un mayor déficit atencional e inhibitorio, predijo una mayor gravedad de los síntomas del TDAH, ii) un mayor déficit atencional e inhibitorio predijo un mayor deterioro funcional, pero no de una manera directa sino a través de los síntomas, y iii) una mayor severidad sintomática predijo una mayor repercusión funcional. Comenzar a explorar y comprender la complejidad del TDAH es clave para avanzar en nuestro conocimiento del trastorno y para la correcta toma de decisiones clínicas.

The development of selective stopping: Qualitative and quantitative changes from childhood to early adulthood.

Although progress has been made in elucidating the behavioral and neural development of global stopping across the lifespan, little is known about the development of selective stopping. This more complex form of inhibitory control is required in real-world situations where ongoing responses must be inhibited to certain stimuli but not others, and can be assessed in laboratory settings using a stimulus selective stopping task. Here we used this task to investigate the qualitative and quantitative developmental changes in selective stopping in a large-scale cross-sectional study with three different age groups (children, preadolescents, and young adults). We found that the ability to stop a response selectively to some stimuli (i.e., use a selective strategy) rather than non-selectively to all presented stimuli (i.e., use a global, non-selective strategy) is fully mature by early preadolescence, and remains stable afterwards at least until young adulthood. By contrast, the efficiency or speed of stopping (indexed by a shorter stop-signal reaction time or SSRT) continues to mature throughout adolescence until young adulthood, both for global and selective implementations of stopping. We also provide some preliminary findings regarding which other task variables beyond the strategy and SSRT predicted age group status. Premature responding (an index of "waiting impulsivity") and post-ignore slowing (an index of cognitive control) were among the most relevant predictors in discriminating between developmental age groups. Although present results need to be confirmed and extended in longitudinal studies, they provide new insights into the development of a relevant form of inhibitory control.

Selective Inhibitory Control in Middle Childhood.

The main aim of this study was to investigate the development of selective inhibitory control in middle childhood, a critical period for the maturation of inhibition-related processes. To this end, 64 children aged 6-7 and 56 children aged 10-11 performed a stimulus-selective stop-signal task, which allowed us to estimate not only the efficiency of response inhibition (the stop-signal reaction time or SSRT), but also the strategy adopted by participants to achieve task demands. We found that the adoption of a non-selective (global) strategy characterized by stopping indiscriminately to all stimuli decreased in older children, so that most of them were able to interrupt their ongoing responses selectively at the end of middle childhood. Moreover, compared to younger children, older children were more efficient in their ability to cancel an initiated response (indexed by a shorter SSRT), regardless of which strategy they used. Additionally, we found improvements in other forms of impulsivity, such as the control of premature responding (waiting impulsivity), and attentional-related processes, such as intra-individual variability and distractibility. The present results suggest that middle childhood represents a milestone in the development of crucial aspects of inhibitory control, including selective stopping.

Physician-perceived utility of the EORTC QLQ-GINET21 questionnaire in the treatment of patients with gastrointestinal neuroendocrine tumours: a multicentre, cross-sectional survey (QUALINETS).

BACKGROUND AND OBJECTIVE: Patient-reported outcome measures can provide clinicians with valuable information to improve doctor-patient communication and inform clinical decision-making. The aim of this study was to evaluate the physician-perceived utility of the QLQ-GINET21 in routine clinical practice in patients with gastrointestinal neuroendocrine tumours (GI-NETs). Secondary aims were to explore the patient, clinician, and/or centre-related variables potentially associated with perceived clinical utility. METHODS: Non-interventional, cross-sectional, multicentre study conducted at 34 hospitals in Spain and Portugal (NCT02853422). Patients diagnosed with GI-NETs completed two health-related quality of life (HRQoL) questionnaires (QLQ-C30, QLQ-GINET21) during a single routine visit. Physicians completed a 14-item ad hoc survey to rate the clinical utility of QLQ-GINET21 on three dimensions: 1)therapeutic and clinical decision-making, 2)doctor-patient communication, 3)questionnaire characteristics. RESULTS: A total of 199 patients at 34 centres were enrolled by 36 participating clinicians. The highest rated dimension on the QLQ-GINET21 was questionnaire characteristics (86.9% of responses indicating "high utility"), followed by doctor-patient communication (74.4%), and therapeutic and clinical decision-making (65.8%). One physician-related variable (GI-NET patient volume > 30 patients/year) was associated with high clinical utility and two variables (older age/less experience treating GI-NETs) with low clinical utility. CONCLUSIONS: Clinician-perceived clinical utility of QLQ-GINET21 is high. Clinicians valued the instruments' capacity to provide a better understanding of patient perspectives and to identify the factors that had the largest influence on patient HRQoL.

Gamma Oscillations in the Temporal Pole Reflect the Contribution of Approach and Avoidance Motivational Systems to the Processing of Fear and Anger Words.

Prior reports suggest that affective effects in visual word processing cannot be fully explained by a dimensional perspective of emotions based on valence and arousal. In the current study, we focused on the contribution of approach and avoidance motivational systems that are related to different action components to the processing of emotional words. To this aim, we compared frontal alpha asymmetries and brain oscillations elicited by anger words associated with approach (fighting) motivational tendencies, and fear words that may trigger either avoidance (escaping), approach (fighting) or no (freezing) action tendencies. The participants' task was to make decisions about approaching or distancing from the concepts represented by words. The results of cluster-based and beamforming analyses revealed increased gamma power band synchronization for fear words relative to anger words between 725 and 750 ms, with an estimated neural origin in the temporal pole. These findings were interpreted to reflect a conflict between different action tendencies underlying the representation of fear words in semantic and emotional memories, when trying to achieve task requirements. These results are in line with the predictions made by the fear-hinders-action hypothesis. Additionally, current data highlights the contribution of motivational features to the representation and processing of emotional words.

The effects of discrimination on the adoption of different strategies in selective stopping.

Selective stopping is demanded in situations where responses must be suppressed to certain signals, but not others. To explore this type of inhibition, the standard stop-signal task has been modified to include a selective implementation of response inhibition by introducing a new stimulus that participants should ignore. However, a stimulus-selective stop-signal task can be performed following different strategies. Some participants fulfill the selective implementation of the stopping process after discriminating the stop and ignore signals, but some others stop the ongoing response whenever any new stimulus appears. The factors that influence this strategy choice are being explored, where both task and participant variables are under consideration. This study aimed to investigate whether the difficulty in discriminating between stop and ignore signals influences strategy adoption. Additionally, we examined whether participants modify their strategy in a flexible manner throughout the task in alternating easy and hard discrimination condition blocks. In the easy discrimination condition, the stop and the ignore signals differed both in color and shape, whereas in the hard discrimination condition, they only differed in shape. Our results from 64 participants revealed that manipulating the difficulty of signal discrimination strongly influenced strategy choice. Also, we found that participants can adapt their strategy according to task demands. They preferentially adopted a selective stopping strategy when discrimination was easy, whereas they changed to a nonselective stopping strategy under the hard discrimination condition. Overall, results from the current study suggest that signal discrimination difficulty influences the adoption of strategies in selective stopping.

Oscillatory brain mechanisms supporting response cancellation in selective stopping strategies.

Although considerable progress has been made in understanding the neural substrates of simple or global stopping, the neural mechanisms supporting selective stopping remain less understood. The selectivity of the stop process is often required in our everyday life in situations where responses must be suppressed to certain signals but not others. Here, we examined the oscillatory brain mechanisms of response cancellation in selective stopping by controlling for the different strategies adopted by participants (n = 54) to accomplish a stimulus selective stop-signal task. We found that successfully cancelling an initiated response was specifically associated with increased oscillatory activity in the high-beta frequency range in the strategy characterized by stopping selectively (the so called dependent Discriminate then Stop, dDtS), but not in the strategy characterized by stopping non-selectively (Stop then Discriminate, StD). Beamforming source reconstruction suggests that this high-beta activity was mainly generated in the superior frontal gyrus (including the pre-supplementary motor area) and the middle frontal gyrus. Present findings provide neural support for the existence of different strategies for solving selective stopping tasks. Specifically, differences between strategies were observed in the oscillatory activity associated with the stop process and were restricted to the high-beta frequency range. Moreover, current results provide important evidence suggesting that high-beta oscillations in superior and middle frontal cortices play an essential role in cancelling an initiated motor response.

Intensive Care to Facilitate Organ Donation: A Report on the Experience of 2 Spanish Centers With a Common Protocol.

BACKGROUND: The aim of this study is to report the experience with a program of Intensive Care to facilitate Organ Donation (ICOD) in 2 Spanish centers based on a common protocol. METHODS: Retrospective review of clinical charts of patients with a devastating brain injury whose families were approached to discuss the possibility of ICOD once further treatment was deemed futile by the treating team. Study period is from January 1, 2011, to December 31, 2015. RESULTS: ICOD was discussed with families of 131 patients. Mean age of possible donors was 75 years (SD = 11 years). The main cause of brain injury was an intracranial hemorrhage (72%). Interviews with families were held after the decision had been made not to intubate/ventilate in 50% of cases, and after the decision not to continue with invasive ventilation in the remaining cases. Most interviews (66%) took place in the emergency department. The majority of families (95%) consented to ICOD. Of the 125 consented cases, 101 (81%) developed brain death (BD), most in 72 hours or less. Ninety-nine (98%) patients transitioned to actual donation after BD, with 1.2 organs transplanted per donor. Of patients who did not evolve to BD, 4 died after an unexpected cardiac arrest and 18 after the withdrawal of life-sustaining measures. ICOD contributed to 33% of actual donors registered at both centers. CONCLUSIONS: ICOD is well accepted by families. Most patients evolve to BD within a short period of time. The practice substantially contributes to increasing organ donation and offers more patients the chance of donating their organs after death.

The association of monoamine-related gene polymorphisms with behavioural correlates of response inhibition: A meta-analytic review.

Response inhibition has been shown to be associated with monoamine-related gene polymorphisms, although evidence is inconclusive. To comprehensively examine these genotype effects on behavioural correlates of response inhibition in non-clinical adult populations, we performed a two-step approach. A systematic review of studies using Go/No-Go and/or Stop-Signal paradigms was first carried out. Thirty-eight eligible research articles were identified, which examined over 15 candidate genes. Remarkably, no firm conclusions could be drawn from these studies. Thus, in a second step, we conducted meta-analyses using random effects models on those polymorphisms that had previously been investigated in at least three studies. Specifically, data from 11 studies was analysed in three meta-analyses for the following polymorphisms: SLC6A3 3'UTR VNTR (k=6 samples; n=1463 participants), COMT Val158Met SNP (k=7 samples; n=784) and SLC6A4 5-HTTLPR (k=4 samples, n=204). None of these polymorphisms showed a reliable association with response inhibition performance. The methodological and theoretical implications of these findings are discussed, along with recommendations for future research.

Prospective validation of a prognostic score for patients in immunotherapy phase I trials: The Gustave Roussy Immune Score (GRIm-Score).

INTRODUCTION: Life expectancy evaluation is crucial when selecting patients who may benefit from phase I studies. The Royal Marsden Hospital (RMH) prognostic score, based on three objective variables (number of metastatic sites, lactate dehydrogenase (LDH) and serum albumin) was validated in patients treated with cytotoxics and targeted therapies. We aimed to determine if those factors were applicable to immune-checkpoint therapies (ICTs) in phase I trials and to evaluate new variables that may preclude a better prognosis in patients receiving ICT. PATIENTS AND METHODS: We conducted a retrospective analysis of survival risk factors in a discovery cohort of 155 patients enrolled into ICT phase I trials at our institution. We computed univariate analysis and multivariate analysis (MVA) of demographics, clinical and biological data to assess their prognostic value for overall survival (OS). MVA results were used to build a prognostic score for OS. A validation cohort of 113 patients enrolled in phase I ICT trials was used to prospectively validate this score. RESULTS: A total of 155 patients (M/F: 83/72; median age 59) receiving an experimental ICT between March 2012 and January 2016 were included in the discovery cohort. An MVA assessing the RMH score variables showed that low albumin (hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.05-2.86) and LDH > upper limit normal (ULN) (HR 1.88, 95% CI 1.12-3.15) were independent negative prognostic factors for OS. Interestingly, neutrophil-to-lymphocyte ratio (NLR) > 6 (HR 1.75, 95% CI 1.04-2.95) was associated with a decrease in OS. The number of metastases was not associated with a poorer outcome for this ICT cohort (HR 0.83, 95% CI 0.51-1.35). A risk score based on the results of the MVA (NLR > 6 = 1; LDH > ULN = 1; albumin < 35 g/l = 1) showed that patients presenting a high score (>1) had a significantly shorter OS (20.4 weeks; 95% CI 5.7-35.2) compared to those with a low score (0 or 1) (68.9 weeks; 95% CI 50-83.7) (HR 2.9, 95% CI 1.87-4.64). In the validation cohort of 113 patients, again the patients presenting a high score showed an inferior OS (HR 6.3, 95% CI 2.7-14.8). CONCLUSION: In ICT phase I trials, traditional prognostic variables included in the RMH score may be suboptimal to determine patient's prognosis. In this context, the NLR is a significant prognostic variable. The Gustave Roussy Immune Score, based on albumin, LDH and NLR, allows a better selection of patients for ICT phase I trials.

Management of Infection and Febrile Neutropenia in Patients with Solid Cancer. / Manejo de la infección y la neutropenia febril en el paciente con cáncer sólido.

A group of experts from the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Medical Oncology (SEOM) have reviewed in this paper the main aspects to be considered in the evaluation of patients with solid cancer and infectious diseases. They have established a series of recommendations on the prevention of the most prevalent infections in these patients, the use of vaccines, the control measures of vascular catheter infection and prevention of infections before certain surgical procedures. Also the criteria for management of febrile neutropenia and the use of colony-stimulating factors were revised. Finally they provide a series of recommendations for the treatment of cancer patients with severe infection. The document is completed with a series of measures for the control of hospital infection.

Neural and behavioral correlates of selective stopping: Evidence for a different strategy adoption.

The present study examined the neural and behavioral correlates of selective stopping, a form of inhibition that has scarcely been investigated. The selectivity of the inhibitory process is needed when individuals have to deal with an environment filled with multiple stimuli, some of which require inhibition and some of which do not. The stimulus-selective stop-signal task has been used to explore this issue assuming that all participants interrupt their ongoing responses selectively to stop but not to ignore signals. However, recent behavioral evidence suggests that some individuals do not carry out the task as experimenters expect, since they seemed to interrupt their response non-selectively to both signals. In the present study, we detected and controlled the cognitive strategy adopted by participants (n=57) when they performed a stimulus-selective stop-signal task before comparing brain activation between conditions. In order to determine both the onset and the end of the response cancellation process underlying each strategy and to fully take advantage of the precise temporal resolution of event-related potentials, we used a mass univariate approach. Source localization techniques were also employed to estimate the neural underpinnings of the effects observed at the scalp level. Our results from scalp and source level analysis support the behavioral-based strategy classification. Specific effects were observed depending on the strategy adopted by participants. Thus, when contrasting successful stop versus ignore conditions, increased activation was only evident for subjects who were classified as using a strategy whereby the response interruption process was selective to stop trials. This increased activity was observed during the P3 time window in several left-lateralized brain regions, including middle and inferior frontal gyri, as well as parietal and insular cortices. By contrast, in those participants who used a strategy characterized by stopping non-selectively, no activation differences between successful stop and ignore conditions were observed at the estimated time at which response interruption process occurs. Overall, results from the current study highlight the importance of controlling for the different strategies adopted by participants to perform selective stopping tasks before analyzing brain activation patterns.

On the violation of causal, emotional, and locative inferences: An event-related potentials study.

Previous event-related potential studies have demonstrated the online generation of inferences during reading for comprehension tasks. The present study contrasted the brainwave patterns of activity to the fulfilment or violation of various types of inferences (causal, emotional, locative). Relative to inference congruent sentence endings, a typical centro-parietal N400 was elicited for the violation of causal and locative inferences. This N400 effect was initially absent for emotional inferences, most likely due to their lower cloze probability. Between 500 and 750ms, a larger frontal positivity (pN400FP) was elicited by inference incongruent sentence endings in the causal condition. In emotional sentences, both inference congruent and incongruent endings exerted this frontally distributed late positivity. For the violation of locative inferences, the larger positivity was only marginally significant over left posterior scalp locations. Thus, not all inference eliciting sentences evoked a similar pattern of ERP responses. We interpret and discuss our results in line with recent views on what the N400, the P600 and the pN400FP brainwave potentials index.

Correlation of hypertension and proteinuria with outcome in elderly bevacizumab-treated patients with metastatic colorectal cancer.

BACKGROUND: Studies suggest a relationship between hypertension and outcome in bevacizumab-treated patients with metastatic colorectal cancer (mCRC). We performed a retrospective analysis of two phase II studies (BECA and BECOX) to determine if hypertension and proteinuria predict outcome in elderly patients with mCRC treated with bevacizumab. PATIENTS AND METHODS: Patients ≥ 70 years of age received either capecitabine 1250 mg/m(2) bid days 1-14 + bevacizumab 7.5 mg/kg day 1 every 21 days (BECA study) or capecitabine 1000 mg/m(2) bid days 1-14 with bevacizumab 7.5 mg/kg and oxaliplatin 130 mg/m(2) day 1 (BECOX study). The primary objective was to correlate hypertension and proteinuria with overall response rate (ORR), time to progression (TTP) and overall survival (OS). Secondary objectives included identification of risk factors associated with the development of hypertension and proteinuria and determining whether development of hypertension or proteinuria in the first 2 cycles was related to ORR, disease-control rate (DCR), TTP or OS. RESULTS: In total, 127 patients (median age 75.5 years) were included in the study. Hypertension correlated with DCR and OS; proteinuria correlated with ORR and DCR. Proteinuria or hypertension in the first 2 cycles did not correlate with efficacy. Risk factors for hypertension were female gender (odds ratio [OR] 0.241; P = 0.011) and more bevacizumab cycles (OR 1.112; P = 0.002); risk factors for proteinuria were diabetes (OR 3.869; P = 0.006) and more bevacizumab cycles (OR 1.181; P<0.0001). Multivariate analysis identified as having prognostic value: baseline lactate dehydrogenase, haemoglobin, number of metastatic lesions and DCR. CONCLUSION: This analysis of two phase II studies suggests that hypertension is significantly correlated with OS but not with ORR and TTP, whereas proteinuria is correlated with ORR but not with OS and TTP. Both hypertension and proteinuria are associated with the duration of bevacizumab treatment and do not represent an independent prognostic factor.