Assessment of algorithms for identifying patients with triple-class refractory multiple myeloma using real-world data.

Objective: Patients with triple-class refractory (TCR) multiple myeloma (MM) have limited treatment options and poor prognoses. This high unmet need has prompted the development of new therapies allowing for improved outcomes for these patients. Recently, new targeted therapies for the treatment of patients with relapsed or refractory MM have been approved based on single-arm clinical trial results. Real-world (RW) data enable a better understanding of the effectiveness of new therapies in clinical practice and provide external controls for single-arm studies. However, using RW data to identify patients with TCR MM is challenging and subject to limitations. Methods: In this retrospective cohort study of an analysis of the COTA electronic health record (EHR) database, we used four algorithms to define refractory status and created four groups of patients with TCR MM initiating post-TCR therapy. Each algorithm relied on slightly different criteria to identify TCR patients, but all were based on the International Myeloma Working Group (IMWG)-derived and/or healthcare provider (HCP)-reported progressions within the database. Results: A total of 3815 patients with newly diagnosed MM met the eligibility criteria for this study. The choice of the algorithm did not impact the characteristics of identified patients with TCR MM (Algorithm 1 [n = 404], Algorithm 2 [n = 123], Algorithm 3 [n = 404], and Algorithm 4 [n = 375]), including their demographic and disease characteristics, MM treatment history, or treatment patterns received after becoming TCR. However, identifying TCR MM using a combination of IMWG-derived and HCP-reported progressions allowed up to a 70% increase in the size of the identified group of patients compared with using only IMWG-derived progressions. Conclusion: In RW settings, progressions from both IMWG-derived data and physician reports may be used to identify patients with TCR MM.

[Exploring the experience of living with a heart transplant: a systematic review of the literature]. / Explorando la experiencia de vivir con un trasplante cardíaco: una revisión sistemática de la literatura.

The focus of healthcare professionals is shifting from illness to health and the individual experience of each person. However, current health care continues to focus on the prevention and treatment of medical complications, leaving aside other important aspects of the experience of cardiac transplant patients. The aim of this systematic review of the literature was to explore how living with a transplanted heart affects their lives. We searched the databases Pubmed, Cinahl, Scielo, Scopus, Dialnet, Cuiden and PsyINFO, and specialized journals. Twenty-five articles were included for study. The analysis and interpretation of the results was based on the methodology by Dixon-Woods et al and by Evans. The results were grouped into seven categories: spiritual repercussions, psychological repercussions, social repercussions, relationship with the donor and the organ, repercussions in the physical environment and quality of life, coping strategies, and feelings towards the healthcare professionals. The results confirm the need for a change in the care given to cardiac transplant patients given that, although transplantation has been shown to improve the quality and quantity of life, it has multiple psychosocial implications that affect the well-being and day-to-day life of these patients.

Explorando la experiencia de vivir con un trasplante cardíaco: una revisión sistemática de la literatura / Exploring the experience of living with a heart transplant: a systematic review of the literature

El enfoque de los profesionales de la salud está cambiando, pasando de centrarse en la enfermedad a orientarse hacia la salud y la experiencia individual de cada persona. Sin embargo, aunque esta perspectiva se considera relevante para los pacientes trasplantados cardíacos, la atención sanitaria actual se sigue centrando en la prevención y el tratamiento de las complicaciones médicas, dejando de lado otros aspectos importantes de su vivencia. El objetivo de esta revisión sistemática de la literatura fue explorar la experiencia de vivir con un corazón trasplantado y las implicaciones vitales que esto supone. Se realizó una búsqueda en las bases de datos Pubmed, Cinahl, Scielo, Scopus, Dialnet, Cuiden y PsyINFO, y en revistas especializadas y se incluyeron 25 artículos cuyo análisis e interpretación se basó en la metodología propuesta por Dixon-Woods y col y por Evans. Los resultados se agruparon en siete categorías: repercusiones espirituales, repercusiones psicológicas, repercusiones sociales, relación con el donante y el órgano, repercusiones en el ámbito físico y calidad de vida, estrategias de afrontamiento, y sentimientos hacia los profesionales. Los resultados confirman la necesidad de que haya un cambio en la atención que se presta a las personas trasplantadas cardíacas. Se ha visto que aunque el trasplante mejora la calidad y la cantidad de vida, tiene múltiples repercusiones psicosociales que afectan al bienestar y al día a día de estos pacientes

The focus of healthcare professionals is shifting from illness to health and the individual experience of each person. However, current health care continues to focus on the prevention and treatment of medical complications, leaving aside other important aspects of the experience of cardiac transplant patiens. The aim of this systematic review of the literature was to explore how living with a transplanted heart affects their lives. We searched the databases Pubmed, Cinahl, Scielo, Scopus, Dialnet, Cuiden and PsyINFO, and specialized journals. Twenty-five articles were included for study. The analysis and interpretation of the results was based on the methodology by Dixon-Woods et al and by Evans. The results were grouped into seven categories: spiritual repercussions, psychological repercussions, social repercussions, relationship with the donor and the organ, repercussions in the physical environment and quality of life, coping strategies, and feelings towards the healthcare professionals. The results confirm the need for a change in the care given to cardiac transplant patients given that, although transplantation has been shown to improve the quality and quantity of life, it has multiple psychosocial implications that affect the well-being and day-to-day life of these patients

Guidelines for seizure management in palliative care: Proposal for an updated clinical practice model based on a systematic literature review. / Guía para el manejo de las crisis epilépticas en cuidados paliativos: propuesta de un modelo actualizado de práctica clínica basado en una revisión sistemática de la literatura.

INTRODUCTION: Very little has been written on seizure management in palliative care (PC). Given this situation, and considering the forthcoming setting up of the Palliative Care Unit at our neurorehabilitation centre, the Clínica San Vicente, we decided to establish a series of guidelines on the use of antiepileptic drugs (AEDs) for handling seizures in PC. METHODS: We conducted a literature search in PubMed to identify articles, recent manuals, and clinical practice guidelines on seizure management in PC published by the most relevant scientific societies. RESULTS: Clinical practice guidelines are essential to identify patients eligible for PC, manage seizures adequately, and avoid unnecessary distress to these patients and their families. Given the profile of these patients, we recommend choosing AEDs with a low interaction potential and which can be administered by the parenteral route, preferably intravenously. Diazepam and midazolam appear to be the most suitable AEDs during the acute phase whereas levetiracetam, valproic acid, and lacosamide are recommended for refractory cases and long-term treatment. CONCLUSIONS: These guidelines provide general recommendations that must be adapted to each particular clinical case. Nevertheless, we will require further well-designed randomised controlled clinical trials including large samples of patients eligible for PC to draft a consensus document recommending adequate, rational, and effective use of AEDs, based on a high level of evidence, in this highly complex area of medical care.

Plasma Aß42/40 Ratio Detects Early Stages of Alzheimer's Disease and Correlates with CSF and Neuroimaging Biomarkers in the AB255 Study.

BACKGROUND: Easily accessible biomarkers are needed for the early identification of individuals at risk of developing Alzheimer's disease (AD) in large population screening strategies. OBJECTIVES: This study evaluated the potential of plasma ß-amyloid (Aß) biomarkers in identifying early stages of AD and predicting cognitive decline over the following two years. DESIGN: Total plasma Aß42/40 ratio (TP42/40) was determined in 83 cognitively normal individuals (CN) and 145 subjects with amnestic mild cognitive impairment (a-MCI) stratified by an FDG-PET AD-risk pattern. RESULTS: Significant lower TP42/40 ratio was found in a-MCI patients compared to CN. Moreover, a-MCIs with a high-risk FDG-PET pattern for AD showed even lower plasma ratio levels. Low TP42/40 at baseline increased the risk of progression to dementia by 70%. Furthermore, TP42/40 was inversely associated with neocortical amyloid deposition (measured with PiB-PET) and was concordant with the AD biomarker profile in cerebrospinal fluid (CSF). CONCLUSIONS: TP42/40 demonstrated value in the identification of individuals suffering a-MCI, in the prediction of progression to dementia, and in the detection of underlying AD pathology revealed by FDG-PET, Amyloid-PET and CSF biomarkers, being, thus, consistently associated with all the well-established indicators of AD.

Correlations between plasma and PET beta-amyloid levels in individuals with subjective cognitive decline: the Fundació ACE Healthy Brain Initiative (FACEHBI).

BACKGROUND: Peripheral biomarkers that identify individuals at risk of developing Alzheimer's disease (AD) or predicting high amyloid beta (Aß) brain burden would be highly valuable. To facilitate clinical trials of disease-modifying therapies, plasma concentrations of Aß species are good candidates for peripheral AD biomarkers, but studies to date have generated conflicting results. METHODS: The Fundació ACE Healthy Brain Initiative (FACEHBI) study uses a convenience sample of 200 individuals diagnosed with subjective cognitive decline (SCD) at the Fundació ACE (Barcelona, Spain) who underwent amyloid florbetaben(18F) (FBB) positron emission tomography (PET) brain imaging. Baseline plasma samples from FACEHBI subjects (aged 65.9 ± 7.2 years) were analyzed using the ABtest (Araclon Biotech). This test directly determines the free plasma (FP) and total plasma (TP) levels of Aß40 and Aß42 peptides. The association between Aß40 and Aß42 plasma levels and FBB-PET global standardized uptake value ratio (SUVR) was determined using correlations and linear regression-based methods. The effect of the APOE genotype on plasma Aß levels and FBB-PET was also assessed. Finally, various models including different combinations of demographics, genetics, and Aß plasma levels were constructed using logistic regression and area under the receiver operating characteristic curve (AUROC) analyses to evaluate their ability for discriminating which subjects presented brain amyloidosis. RESULTS: FBB-PET global SUVR correlated weakly but significantly with Aß42/40 plasma ratios. For TP42/40, this observation persisted after controlling for age and APOE ε4 allele carrier status (R2 = 0.193, p = 1.01E-09). The ROC curve demonstrated that plasma Aß measurements are not superior to APOE and age in combination in predicting brain amyloidosis. It is noteworthy that using a simple preselection tool (the TP42/40 ratio with an empirical cut-off value of 0.08) optimizes the sensitivity and reduces the number of individuals subjected to Aß FBB-PET scanners to 52.8%. No significant dependency was observed between APOE genotype and plasma Aß measurements (p value for interaction = 0.105). CONCLUSION: Brain and plasma Aß levels are partially correlated in individuals diagnosed with SCD. Aß plasma measurements, particularly the TP42/40 ratio, could generate a new recruitment strategy independent of the APOE genotype that would improve identification of SCD subjects with brain amyloidosis and reduce the rate of screening failures in preclinical AD studies. Independent replication of these findings is warranted.

Current evidence on transcranial magnetic stimulation and its potential usefulness in post-stroke neurorehabilitation: Opening new doors to the treatment of cerebrovascular disease. / Evidencias actuales sobre la estimulación magnética transcraneal y su utilidad potencial en la neurorrehabilitación postictus: Ampliando horizontes en el tratamiento de la enfermedad cerebrovascular.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) is a therapeutic reality in post-stroke rehabilitation. It has a neuroprotective effect on the modulation of neuroplasticity, improving the brain's capacity to retrain neural circuits and promoting restoration and acquisition of new compensatory skills. DEVELOPMENT: We conducted a literature search on PubMed and also gathered the latest books, clinical practice guidelines, and recommendations published by the most prominent scientific societies concerning the therapeutic use of rTMS in the rehabilitation of stroke patients. The criteria of the International Federation of Clinical Neurophysiology (2014) were followed regarding the inclusion of all evidence and recommendations. CONCLUSIONS: Identifying stroke patients who are eligible for rTMS is essential to accelerate their recovery. rTMS has proven to be safe and effective for treating stroke complications. Functional brain activity can be optimised by applying excitatory or inhibitory electromagnetic pulses to the hemisphere ipsilateral or contralateral to the lesion, respectively, as well as at the level of the transcallosal pathway to regulate interhemispheric communication. Different studies of rTMS in these patients have resulted in improvements in motor disorders, aphasia, dysarthria, oropharyngeal dysphagia, depression, and perceptual-cognitive deficits. However, further well-designed randomized controlled clinical trials with larger sample size are needed to recommend with a higher level of evidence, proper implementation of rTMS use in stroke subjects on a widespread basis.

FACEHBI: A Prospective Study of Risk Factors, Biomarkers and Cognition in a Cohort of Individuals with Subjective Cognitive Decline. Study Rationale and Research Protocols.

BACKGROUND: Long-term longitudinal studies with multimodal biomarkers are needed to delve into the knowledge of preclinical AD. Subjective cognitive decline has been proposed as a risk factor for the development of cognitive impairment. Thus, including individuals with SCD in observational studies may be a cost-effective strategy to increase the prevalence of preclinical AD in the sample. OBJECTIVES: To describe the rationale, research protocols and baseline characteristics of participants in the Fundació ACE Healthy Brain Initiative (FACEHBI). DESIGN: FACEHBI is a clinical trial (EudraCT: 2014-000798-38) embedded within a long-term observational study of individuals with SCD. SETTING: Participants have been recruited at the memory clinic of Fundació ACE (Barcelona) from two different sources: patients referred by a general practitioner and individuals from an Open House Initiative. PARTICIPANTS: 200 individuals diagnosed with SCD with a strictly normal performance in a comprehensive neuropsychological battery. MEASUREMENTS: Individuals will undergo an extensive neuropsychological protocol, risk factor assessment and a set of multimodal biomarkers including florbetaben PET, structural and functional MRI, diffusion tensor imaging, determination of amyloid species in plasma and neurophthalmologic assessment with optical coherence tomography. RESULTS: Two hundred individuals have been recruited in 15 months. Mean age was 65.9 years; mean MMSE was 29.2 with a mean of 14.8 years of education. CONCLUSIONS: FACEHBI is a long-term study of cognition, biomarkers and lifestyle that has been designed upon an innovative symptom-based approach using SCD as target population. It will shed light on the pathophysiology of preclinical AD and the role of SCD as a risk marker for the development of cognitive impairment.

Factors affecting nursing staff use of a communication tool to reduce potentially preventable acute care transfers in long-term care.

Although specialized communication tools can effectively reduce acute care transfers, few studies have assessed the factors that may influence the use of such tools by nursing staff at the individual level. We evaluated the associations between years of experience, tool-related training, nursing attitudes, and intensity of use of a communication tool developed to reduce transfers in a long-term care facility. We employed a mixed methods design using data from medical charts, electronic records, and semi-structured interviews. Experienced nurses used the tool significantly less than inexperienced nurses, and training had a significant positive impact on tool use. Nurses found the purpose of the tool to be confusing. No significant differences in attitude were observed based on years of experience or intensity of use. Project findings indicate that focused efforts to enrich training may increase intervention adherence. Experienced nurses in particular should be made aware of the benefits of utilizing communication tools.

Mortality risk of sotalol and amiodarone for post-CABG atrial fibrillation.

BACKGROUND: Sotalol and amiodarone are commonly prescribed antiarrhythmics for the treatment of post-operative atrial fibrillation (POAF). Though they are effective in maintaining sinus rhythm in this population, little is known about their association with mortality. OBJECTIVES: To examine the association between sotalol and amiodarone exposure and total mortality in individuals with new-onset POAF following CABG. METHODS: The computerised health databases of Quebec, Canada were used to identify all patients over 65 who had undergone CABG and were newly diagnosed with POAF (January 1993 to June 2003). A time-matched nested-case-control approach was used to compare current users of sotalol and amiodarone with those not exposed to either medication during the same period. Rate ratios of mortality were estimated using conditional logistic regression. RESULTS: 4770 eligible patients were identified (930 cases, 4648 matched controls). Sotalol users had fewer comorbidities and used fewer concomitant medications than amiodarone users at baseline. Current users of sotalol were at decreased risk of mortality compared to individuals not exposed to either study drug during the same period (RRadj. 0.56 (0.39, 0.80)) while current users of amiodarone were at increased risk of mortality (RRadj. 1.50 (1.15, 1.94)). However this association was not consistently observed across all sensitivity and subgroup analyses. CONCLUSIONS: Current use of sotalol was associated with a decreased risk of mortality. Current use of amiodarone was associated with an increased risk of mortality but not for all subgroups. Additional research is required to better understand the safety of sotalol and amiodarone in individuals with POAF.

Beyond the Controversy on Aß Blood-Based Biomarkers.

Central biomarkers of Alzheimer's disease (AD) have been proven to have diagnostic and prognostic capacity. However, both amyloid positron emission tomography and cerebrospinal fluid collection studies present problems that limit their widespread acceptability in global clinical trials. Thus, development of other measures as potential surrogates of amyloid positivity should be pursued. Results from numerous experimental studies strongly suggest that the association between Aß plasma levels, particularly the Aß42/Aß40 ratio, and AD diagnosis goes beyond what could be attributable to pure chance, although this association is still controversial. The aim of this review is to consider selected works that may help to improve the design of blood based biomarkers studies by controlling a number of confounding sources related to the clinical gold standard, the time-course of central and peripheral biomarkers, and the metabolism of Aß in blood that may be blurring the presumptive association between Aß blood levels and AD. Based on these data and to get pass the controversy, we tentatively postulate that at early stages of preclinical AD, blood Aß levels and central Aß biomarkers would follow parallel but temporally displaced trajectories. This association would become eventually lost as the disease progresses and the clearance mechanisms in the blood brain barrier are increasingly impaired.

The impact of antibiotics on growth in children in low and middle income countries: systematic review and meta-analysis of randomised controlled trials.

OBJECTIVES: To determine whether antibiotic treatment leads to improvements in growth in prepubertal children in low and middle income countries, to determine the magnitude of improvements in growth, and to identify moderators of this treatment effect. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, Embase, Scopus, the Cochrane central register of controlled trials, and Web of Science. STUDY SELECTION: Randomised controlled trials conducted in low or middle income countries in which an orally administered antibacterial agent was allocated by randomisation or minimisation and growth was measured as an outcome. Participants aged 1 month to 12 years were included. Control was placebo or non-antimicrobial intervention. RESULTS: Data were pooled from 10 randomised controlled trials representing 4316 children, across a variety of antibiotics, indications for treatment, treatment regimens, and countries. In random effects models, antibiotic use increased height by 0.04 cm/month (95% confidence interval 0.00 to 0.07) and weight by 23.8 g/month (95% confidence interval 4.3 to 43.3). After adjusting for age, effects on height were larger in younger populations and effects on weight were larger in African studies compared with other regions. CONCLUSION: Antibiotics have a growth promoting effect in prepubertal children in low and middle income countries. This effect was more pronounced for ponderal than for linear growth. The antibiotic growth promoting effect may be mediated by treatment of clinical or subclinical infections or possibly by modulation of the intestinal microbiota. Better definition of the mechanisms underlying this effect will be important to inform optimal and safe approaches to achieving healthy growth in vulnerable populations.

Changes in the brain and plasma Aß peptide levels with age and its relationship with cognitive impairment in the APPswe/PS1dE9 mouse model of Alzheimer's disease.

Double transgenic mice expressing mutant amyloid precursor protein (APPswe) and mutant presenilin 1 (PS1dE9) are a model of Alzheimer-type amyloidosis and are widely used in experimental studies. In the present work, the relationships between brain and plasma amyloid-ß peptide (Aß) levels and cognitive impairments were examined in male APPswe/PS1dE9 double transgenic mice at different ages. When compared with non-transgenic littermates, APPswe/PS1dE9 mice exhibited significant learning deficits from the age of 6months (M6), which were aggravated at later stages of life (M8 and M12). Sporadic brain amyloid plaques were observed in mice as early as M3 and progressively increased in number and size up to M12. A similar increase was observed in brain insoluble Aß levels as assessed by enzyme-linked immunosorbent assay (ELISA). In particular, the levels of brain insoluble Aß peptides rose steeply from M4 to M6. Interestingly, this pronounced amyloid deposition was accompanied by a temporary fall in the concentration of brain soluble and membrane-bound Aß peptides at M6 that rose again at M8 and M12. The plasma levels of Aß40 and Aß42 decreased with advancing age up to M8, when they stabilized at M12. This decrease in plasma Aß levels coincided with the observed increase in insoluble brain Aß levels. These results could be useful for developing plasma Aß levels as possible biomarkers of the cerebral amyloidosis and provide advances in the knowledge of the Aß peptide biochemical changes that occur in the brain of Alzheimer's disease patients.

[Nephrotoxicity due to iodine contrasts in computerized tomography studies of diabetic outpatients on metformin]. / Nefrotoxicidad por contrastes yodados en estudios de tomografía computarizada a pacientes ambulatoriso diabéticos en tratamiento con metformina.

BACKGROUND: To determine the incidence of contrast-induced nephropathy (CIN) among diabetic patients treated with Metformin who underwent computerized tomography (CT) scan with iodinated contrast media. METHODS: Prospective study of diabetic patients enrolled in a lactic acidosis prevention protocol in whom clinical and analytical follow up after CT scan with intravenous contrast was performed. RESULTS: In this study, 98 cases were collected. The incidence of CIN in diabetic patients without prior renal failure was 0%. In patients with previous renal failure the incidence of CIN was 4.7%. CONCLUSIONS: The risk of CIN in diabetic patients with no renal failure undergoing intravenous contrast administration is minimal. Recommendations to stop Metformin to avoid lactic acidosis in patients undergoing intravenous contrast administration may be restricted to patients with abnormal renal function.

Effect of age and severity of cognitive dysfunction on two simple tasks in pet dogs.

Dogs exhibit age-dependent losses in learning and memory as well as a progressive accumulation of neuropathology that parallels that observed in normal human aging and early Alzheimer's disease. These deficits have been extensively studied using a number of standard cognitive tasks in the laboratory; however, appropriate tools for their assessment in veterinary clinics are still lacking. The aim of this study was to evaluate the effect of age and the severity of cognitive dysfunction syndrome (CDS) on two simple tests conducted in a clinical setting. A food searching (FS) task and a problem-solving (PS) task were administered to young (1-4 years, n=9), middle-aged (5-8 years, n=10), cognitively unimpaired aged (≥9 years, n=31), and cognitively impaired aged (≥ 9 years, n=37) dogs. Cognitive status was classified using an owner-based questionnaire, and in the impaired group, dogs were categorized as having either mild or severe CDS. During the FS task, younger dogs (<9 years) were able to locate the food more quickly and with more success than the aged groups (≥9 years). Dogs with severe CDS exhibited poorer performance than those with mild CDS or their healthy counterparts. In the PS task, younger dogs performed better than the aged dogs in obtaining food, but there were no differences related to CDS severity. The FS task might help to better characterize cognitively affected dogs in the clinical setting than the PS task. These and similar tasks require further investigations in the field.

Nefrotoxicidad por contrastes yodados en estudios de tomografía computarizada a pacientes ambulatorios diabéticos en tratamiento con metformina / Nephrotoxicity due to iodine contrasts in computerized tomography studies of diabetic outpatients on metformin

Fundamento. Determinar la incidencia de nefropatía inducida por contraste (NIC) en un grupo de pacientes diabéticos en tratamiento con metformina a los que se realiza un estudio de tomografía computarizada (TC)con contraste yodado intravenoso (civ). Material y Métodos. Estudio prospectivo de pacientes diabéticos incluidos en el protocolo para la prevención de la acidosis láctica a los que se hace seguimiento clínico y analítico tras la realización de una TC con civ. Resultados. Se recogieron 98 casos. En los pacientes sin insuficiencia renal previa la incidencia de NIC es del 0%. En los pacientes con insuficiencia renal previa la incidencia de NIC es del 4,7%. Conclusiones. El riesgo de NIC en pacientes diabéticos sin insuficiencia renal a los que se administra contraste yodado es mínimo. Las recomendaciones de retirar la metformina para evitar la acidosis láctica en pacientes a los que se administra civ se podría limitar a los pacientes con alteración de la función renal (AU)

Background. To determine the incidence of contrast induced nephropathy (CIN) among diabetic patients treated with Metformin who underwent computerized tomography (CT) scan with iodinated contrast media. Methods. Prospective study of diabetic patients enrolled in a lactic acidosis prevention protocol in whom clinical and analytical follow up after CT scan with intravenous contrast was performed. Results. In this study, 98 cases were collected. The incidence of CIN in diabetic patients without prior renal failure was 0%. In patients with previous renal failure the incidence of CIN was 4.7%. Conclusions. The risk of CIN in diabetic patients with no renal failure undergoing intravenous contrast administration is minimal. Recommendations to stop Metformin to avoid lactic acidosis in patients undergoing intravenous contrast administration may be restricted to patients with abnormal renal function (AU)

Effect of age and severity of cognitive dysfunction on spontaneous activity in pet dogs - part 1: locomotor and exploratory behaviour.

Age-related cognitive dysfunction syndrome (CDS) has been reported in dogs and it is considered a natural model for Alzheimer's disease in humans. Changes in spontaneous activity (including locomotor and exploratory behaviour) and social responsiveness have been related to the age and cognitive status of kennel-reared Beagle dogs. The aim of this study was to assess the influence of age and severity of CDS on locomotor and exploratory behaviour of privately owned dogs. This is the first part of a two-part report on spontaneous activity in pet dogs. An open-field (OF) test and a curiosity test were administered at baseline and 6 months later to young (1-4 years, n=9), middle-aged (5-8 years, n=9), cognitively unimpaired aged (≥ 9 years, n=31), and cognitively impaired aged ( ≥ 9 years, n=36) animals. Classification of cognitive status was carried out using an owner-based observational questionnaire, and in the cognitively impaired group, the dogs were categorised as having either mild or severe cognitive impairment. Dogs were recorded during sessions in the testing room and the video-recordings were subsequently analysed. The severity of CDS (but not age) influenced locomotion and exploratory behaviour so that the more severe the impairment, the higher the locomotor activity and frequency of corner-directed (aimless) behaviours, and the lower the frequency of door-aimed activities. Curiosity directed toward novel stimuli exhibited an age-dependent decline although severely affected animals displayed more sniffing episodes directed towards the objects. OF activity did not change after 6 months. Testing aged pet dogs for spontaneous behaviour might help to better characterise cognitively affected individuals.

Effect of age and severity of cognitive dysfunction on spontaneous activity in pet dogs - part 2: social responsiveness.

Changes in social interactions with owners and other dogs are frequently observed in dogs with cognitive dysfunction syndrome (CDS). The aim of this work was to assess the effect of age and severity of CDS on social responsiveness. This is the second part of a 2-part report on spontaneous activity in pet dogs. A human interaction test and a mirror test were administered at baseline and 6 months later to assess social responses to humans and conspecifics, respectively, to four groups of privately-owned dogs: young (n=9), middle-aged (n=9), cognitively unimpaired aged (n=31), and cognitively impaired aged (n=36). The severity of cognitive impairment was considered in the last group and dogs were categorised as having either mild or severe CDS. The influence of the person and the mirror on locomotion and exploratory behaviour was also studied. Dogs were recorded in a testing room and the video recordings were subsequently analysed. Young dogs displayed more interactions involving physical contact with a person. Young and middle-aged dogs showed more vocalisations in response to social isolation. In contrast, aged animals spent more time in front of the mirror. Changes in social responsiveness associated with severe CDS included decreased response to social isolation and human interaction and increased time in front of the mirror, suggesting a deficit in habituation. Testing of spontaneous activity might help to characterise CDS in aged dogs, a condition increasingly diagnosed in veterinary clinics and a potentially useful natural model of Alzheimer's disease in humans.

Embolización directa de varices estomales en la hipertensión portal tras el tratamiento de metástasis hepáticas / Direct embolization of stomal varices in portal hypertension after the treatment of liver metastases

Se presenta el caso de un paciente con antecedentes de carcinoma colorrectal y afectación metastásica hepática multitratada con quimioterapia intraarterial con oxaliplatino y radioembolización con microesferas de Ytrio-90, que desarrolló una hipertensión portal secundaria a dichos tratamientos y sangrados recurrentes por varices estomales. El tratamiento definitivo de los episodios de sangrado consistió en la embolización con espirales (coils) de las varices mediante un abordaje percutáneo directo de las mismas (AU)

We present the case of a man with a history of colorectal carcinoma and metastatic liver involvement who developed portal hypertension and recurrent bleeding from stomal varices after treatment with intra-arterial oxaliplatin and radioembolization with yttrium-90 microspheres. The definitive treatment for the bleeding episodes was embolization of the varices with coils using a direct percutaneous approach (AU)