Característiques dels pacients inclosos als assaigs clínics amb fàrmacs inhibidors del sistema renina-angiotensina : Revisió sistemàtica

Objectiu: Descriure les característiques demogràfiques i clíniques dels pacients inclosos als assaigs clínics que avaluen l’eficàcia dels fàrmacs inhibidors del sistema renina-angiotensina (ISRA). Metodologia: Revisió sistemàtica dels assaigs clínics que avaluen l’eficàcia dels ISRA, a partir de la base de dades bibliogràfica Cochrane Plus. A partir dels 143 articles identificats, es van recollir els criteris de selecció i les característiques demogràfiques i clíniques dels pacients tractats amb ISRA. Resultats: El criteri d’inclusió més freqüent dels pacients va ser la hipertensió arterial (111 assaigs) i el d’exclusió l’alteració de la funció renal (68 assaigs). Dels 64.038 pacients inclosos, 38.106 van rebre tractament amb ISRA. Les dades disponibles dels pacients tractats amb ISRA van ser: edat (68,5%), sexe (88,7%), pes (16,2%), pressió arterial sistòlica i diastòlica (67,7%), creatinina (22,8%). L’edat (SD) mitjana dels pacients va ser de 53,1 (7) anys, el 38,1% van ser dones i la concentració de creatinina (SD) mitjana dels pacients va ser d’1,2 (0,3) mg/dl. Conclusió: Hi ha poca informació sobre les característiques demogràfiques i clíniques dels pacients en les publicacions dels assaigs clínics que avaluen l’eficàcia dels ISRA. Els pacients inclosos tenen una edat mitjana d’uns 50 anys, la majoria són homes i tenen una funció renal conservada.

Estudi comparatiu de combinacions de dosis fixes enfront a dosis lliures en el control de la tensió arterial, factors que determinen el seu ús i impacte assistencial sanitari

Es tracta d’un estudi de cohorts prospectiu històric que pretén comparar l’ús de combinacions de dosis lliures enfront a les combinacions de dosis fixes en el control de la tensió arterial pel que fa a eficàcia i assoliment dels objectius terapèutics per al tractament d’aquesta patologia tan prevalent a les societats desenvolupades, així com comparar l’impacte econòmico-sanitari que comporten una i altra pel que fa a número de visites mèdiques, d’infermeria i número d’analítiques que es requereixen en cada estratègia. L’estudi també pretén analitzar els factors que determinen l’ús d’unes o altres en el tractament de la hipertensió arterial.

Pacientes de edad avanzada con insuficiencia cardíaca ingresados en un servicio de medicina interna: valoración de la función renal.

Objectius: analitzar comorbiditats de pacients hospitalaris ≥65 anys amb Insuficiència Cardíaca (IC). Adequació tractament farmacològic. Impacte Insuficiència Renal (IR). Metodologia: estudi descriptiu transversal de 150 pacients ingressats en Medicina Interna Hospital Vall d'Hebron entre juny'2007-gener'2010. Resultats: hipertensió arterial: 84%; obesitat: 32,1%; cardiopatia isquèmica: 41,3%; fracció d'ejecció del ventricle esquerre (FEVI) conservada: 70%. 53 pacients sense antagonistes de l'enzim convertidor de l'angiotensina, 105 sense βBloquejants i 55 sense antialdosterònics. Prevalença IR: 70%. Factors de risc: HTA, sexe femení. IC+IR+anèmia: 66 pacients, 2 tractament amb eritropoetina. Conclusions: IC de causa hipertensiva, amb FEVI conservada. Mala adequació tractament. Elevada prevalença IR. Importància Síndrome cardiorenal.

Gamma Knife, CyberKnife, TomoTherapy: gadgets or useful tools?

Purpose of reviewThis review provides information and an update on stereotactic radiosurgery (SRS) equipment, with a focus on intracranial lesions and brain neoplasms.Recent findingsGamma Knife radiosurgery represents the gold standard for intracranial radiosurgery, using a dedicated equipment, and has recently evolved with a newly designed technology, Leksell Gamma Knife Perfexion. Linear accelerator-based radiosurgery is more recent, and originally based on existing systems, either adapted or dedicated to radiosurgery. Equipment incorporating specific technologies, such as the robotic CyberKnife system, has been developed. Novel concepts in radiation therapy delivery techniques, such as intensity-modulated radiotherapy, were also developed; their integration with computed tomography imaging and helical delivery has led to the TomoTherapy system. Recent data on the management of intracranial tumors with radiosurgery illustrate the trend toward a larger use and acceptance of this therapeutic modality.SummarySRS has become an important alternative treatment for a variety of lesions. Each radiosurgery system has its advantages and limitations. The 'perfect' and ubiquitous system does not exist. The choice of a radiosurgery system may vary with the strategy and needs of specific radiosurgery programs. No center can afford to acquire every technology, and strategic choices have to be made. Institutions with large neurosurgery and radiation oncology programs usually have more than one system, allowing optimization of the management of patients with a choice of open neurosurgery, radiosurgery, and radiotherapy. Given its minimally invasive nature and increasing clinical acceptance, SRS will continue to progress and offer new advances as a therapeutic tool in neurosurgery and radiotherapy.

Factores de riesgo cardiovascular en una población de trasplantados hepáticos con supervivencia superior a diez años. Estudio específico de la hipertensión arterial.

Introducció: Els factors de risc cardiovascular originen un problema de salut pública important. El transplant hepàtic pot ocasionar una modificació del seu desenvolupament degut a la immunosupressió, però hi ha pocs estudis que evaluen estos aspectes en pacients amb una supervivència llarga. El nostre objectiu es analitzar l'efecte de la hipertensió arterial (HTA) posttrasplantament sobre la supervivència a llarg termini d'una cohort de pacients trasplantats amb més de deu anys de seguiment. Metodologia: S'estudiaren restrospectivament els pacients trasplantats al nostre centre per totes les causes, des de 2001 fins 2007, amb una supervivència mínima de deu anys. S'analitzaren dades demogràfiques, clíniques, analítiques e histològiques del pre i/o postrasplant. Resultats: La prevalència dels factors de risc cardiovascular va ser molt freqüent durant el primer any: obesitat 24.5%, HTA 67%, diabetes 22.5%, dislipèmia46.5% i insuficiència renal crónica 28%. La HTA es el factor de risc més prevalent i la seua incidència augmenta amb el temps de 67% al 72,5% entre el primer i desè any. La HTA pareix asociar-se a una major mortalitat posttrasplantament i a una major incidència d'enfermetat cardiovascular (p&0.005). Els factors de risc asociats amb el desenvolupament de HTA en la nostra població son l'edat, l'obesitat i la dislipèmia. Conclusió: Es important disenyar estratègies per al millor control de la HTA des del posttrasplantament inicial, degut a la seua repercusió negativa sobre les enfermetats cardiovasculars i la supervivència, així com per a l'obesitat i la dislipèmia, ja que son co-factors de desenvolupament de l'HTA.

Troubles cognitifs séquellaires de la rupture d'anévrysmes de l'artère communicante antérieure et de l'artère cérébrale antérieure. Etude rétrospective de 56 cas [Cognitive sequelae following rupture of aneurysms of the anterior communicating artery and the anterior cerebral artery. Retrospective study of 56 cases].

The neuropsychological records of 56 patients operated for clipping were studied. Almost every patient remained autonomous and without invalidating motor defect. The present study was aimed at specifying the type and frequency of neuropsychological sequelae and, to a lesser extent, the role of various pathophysiological factors. A main concern was to examine to what extent and at what post-operative interval the neuropsychological assessment can predict the intellectual and socioprofessional outcome of each individual patient. The neuropsychological assessment performed beyond the acute phase showed evidence of intellectual sequelae in about two thirds of the patients. Only one case of permanent anterograde amnesia was observed, probably due to unavoidable inclusion of a hypothalamic artery in the clip during surgery. Transient anterograde amnesia and confabulations were occasionally observed, generally for less than three weeks. A common finding was impaired performance on memory and/or executive tests. In a minority of patients, language disorders, visuoperceptive and visuoconstructive disabilities were found, probably in relation with hemodynamic changes at distance from the aneurysm. Global impairment of intellectual function was not uncommon in the acute post-operative phase but it evolved in most cases towards a more selective impairment, for instance restricted to executive and memory functions, in the chronic phase. The neuropsychological investigation carried out 4 to 15 weeks post-operatively provided satisfactory information about possible long-lasting intellectual disturbances and professional resumption. In particular, persistent global intellectual impairment, persistent amnesia and confabulations 4-15 weeks post-operative were associated with cessation of professional activity; executive and memory impairment, behavioral disturbances such as those encountered in patients with frontal lobe damage were associated with a decreased probability of full-time employment. Pre- and post-operative angiography were not good predictors of long-term cognitive outcome: normal angiography was not necessarily followed by normal neuropsychological outcome, conversely abnormal angiography could be found together with normal neuropsychological outcome. By contrast, there was a relationship between left-lateralised abnormalities on post-operative angiography and occurrence of language disorders; similarly, there was a relationship between side of craniotomy and type of deficits, that is language disorders versus visuoperceptive-visuoconstructive impairments.

Renograma 99mTc Post-Captoprilen la valoración de la hipertensión vásculo-renal en pacientes portadores de injerto renal.

Objectiu: Descripció de la metodologia del renograma isotòpic basal/postcaptopril (RIB/P) en pacients portadors de empelt renal amb sospita de malaltia vasculo-renal (MVR). Material i mètodes: Es va realitzar en 44 pacients trasplantats renals un renograma basal i 48 hores després un renograma postcaptopril administrant 25 mg de captopril v.o i realitzant una adquisició 30 minuts després. Resultats: Dels 44 estudis 6 van ser positius, constatant-se MVR per angio-TC i 38 van ser negatius tractats posteriorment amb IECAs o ARAII i no van mostrar alteracions significatives del funcionalisme renal. Conclusions: El RIB/P es una eina útil para determinar MVR en pacients amb empelt renal i hipertensió arterial.

Second cranio-facial malignancies in hereditary retinoblastoma survivors previously treated with radiation therapy: clinic and radiologic characteristics and survival outcomes.

INTRODUCTION: Hereditary retinoblastoma survivors have an increased risk for cranio-facial second primary tumours (SPT), especially after treatment with external beam radiotherapy (EBRT). This multicentre study evaluates the clinical and imaging characteristics and outcomes of cranio-facial SPTs in irradiated retinoblastoma survivors. PATIENTS AND METHODS: Clinical and radiological data of 42 hereditary retinoblastoma patients with 44 second and third malignancies were reviewed. Radiological data included anatomic location and computed tomography (CT) and magnetic resonance (MR) characteristics. Cox regression and likelihood ratio chi-square test were used to evaluate differences in patients' survival rates. RESULTS: Cranio-facial SPTs were diagnosed at a median age of 13 years. Histological types included osteosarcomas (43%), rhabdomyosarcomas (20%) (57% embryonal, 43% alveolar) and a variety of other types of SPT (37%). Predilection sites were: temporal fossa (39%), ethmoid sinus (23%), orbit (18%), maxillary sinus (16%) and intracranial dura mater (4%). Most of the osteosarcomas (78%) and rhabdomyosarcomas (80%) occurred in patients treated with EBRT in the first year-of-life. Treatment of SPTs with a microscopically complete surgical resection led to a significantly better 5-year overall survival (OS) (P=0.017) and event-free survival (EFS) (P=0.012) compared to patients treated without surgery or incomplete resection (OS: 83% versus 52%; EFS: 80% versus 47%). CONCLUSIONS: Osteosarcomas and rhabdomyosarcomas are the most common cranio-facial SPTs in irradiated hereditary retinoblastoma survivors, which develop in specific locations and occur predominantly in patients irradiated in their first year-of-life. Microscopically complete surgical resection of SPTs is a major prognostic factor, suggesting the potential benefit of early detection by imaging.

Taille et localisation des anévrismes intracraniens rompus et facteurs de risque de rupture

Question de recherche : Est-ce que la limite de taille de 7 mm d'un anévrisme intracrânien non rompu¦proposée par les études internationales est un critère valable de sélection entre un traitement¦conservateur (observation périodique) ou une intervention curative sur la population du CHUV ?¦Contexte : On estime actuellement la fréquence des anévrismes intracrâniens à 0.2-9% dans la¦population générale. Le taux d'hémorragie sous-arachnoïdienne due à une rupture d'anévrisme est¦estimé à 6-16 pour 100'000 personnes.¦Selon les investigateurs de l'International Study of Unruptured Intracranial Aneurysms (ISUIA, 2003),¦le taux cumulé de rupture à 5 ans pour les anévrismes de moins de 7 mm de diamètre est de 0.05% ou¦2.5% selon que l'anévrisme se situe sur une artère de la circulation cérébrale antérieure ou postérieure,¦respectivement.¦Ces chiffres sont fortement controversés. En effet, d'autres études montrent que le risque de rupture des¦anévrismes inférieurs à 7 mm de diamètre est bien plus important que ne le laisse supposer l'étude¦ISUIA.¦Objectifs : L'objectif de ce travail de maîtrise vise à déterminer si la limite de taille de 7 mm d'un¦anévrisme cérébral non rompu proposé par certaines études internationales (et notamment l'étude¦ISUIA) est un critère valable pour sélectionner entre une observation périodique ou une intervention¦curative (chirurgicale ou endovasculaire) des patients.¦Un corollaire qui découle de cette question est de savoir s'il est justifié de traiter d'emblée un¦anévrisme cérébral non rompu mesurant moins de 7 mm.¦Matériel et Méthodes : Etude rétrospective observationnelle basée sur des données provenant des¦dossiers médicaux des patients admis aux urgences du CHUV avec une hémorragie sousarachnoïdienne¦due à la rupture d'un anévrisme intracrânien pendant une période allant de juin 2005 à¦avril 2011.¦Différents paramètres sont pris en considération : l'âge et le sexe du patient, la taille, la localisation et le¦nombre d'anévrismes, les facteurs de risque de rupture comme le tabac, l'hypertension artérielle et la¦consommation d'alcool, ainsi que les antécédents et l'histoire familiale de rupture d'anévrisme.¦Le critère de jugement principal est la taille de l'anévrisme, suivi par sa localisation.¦Les critères d'exclusion des patients sont les suivants : anévrismes mycotique, fusiforme ou¦traumatique, tumeur cérébrale maligne.¦Résultats escomptés : Avec ce travail, une nouvelle limite de diamètre anévrismal pourrait être¦proposée, en tenant compte des différents paramètres analysés sur un échantillon de la population¦locale. Les résultats pourraient apporter plus de précisions dans le bilan du risque d'une rupture¦anévrismale. Ainsi, la décision d'une intervention bénéficierait d'une base de réflexion nouvelle pour¦les anévrismes non rompus de petite taille.¦Plus-value escomptée : Cette étude pourrait contribuer à améliorer le pronostic des patients porteurs¦d'anévrisme(s) intracrânien(s). Elle permettrait en effet d'intervenir en cas d'anévrismes intracrâniens¦non rompus de taille inférieure à 7 mm, avant que ceux-ci ne se rompent et provoquent une hémorragie¦sous-arachnoïdienne.

Early white matter alterations in men predisposed to FXTAS revealed by MT imaging.

Introduction: The Fragile X - associated Tremor Ataxia Syndrome (FXTAS) is a recently described, and under-diagnosed, late onset (≈ 60y) neurodegenerative disorder affecting male carriers of a premutation in the Fragile X Mental Retardation 1 (FMR1) gene. The premutation is an CGG (Cytosine-Guanine-Guanine) expansion (55 to 200 CGG repeats) in the proximal region of the FMR1 gene. Patients with FXTAS primarily present with cerebellar ataxia and intention tremor. Neuroradiological features of FXTAS include prominent white matter disease in the periventricular, subcortical, middle cerebellar peduncles and deep white matter of the cerebellum on T2-weighted or FLAIR MR imaging (Jacquemmont 2007, Loesch 2007, Brunberg 2002, Cohen 2006). We hypothesize that a significant white matter alteration is present in younger individuals many years prior to clinical symptoms and/or the presence of visible lesions on conventional MR sequences and might be detectable by magnetization transfer (MT) imaging. Methods: Eleven asymptomatic premutation carriers (mean age = 55 years) and seven intra-familial controls participated to the study. A standardized neurological examination was performed on all participants and a neuropsychological evaluation was carried out before MR scanning performed on a 3T Siemens Trio. The protocol included a sagittal T1-weighted 3D gradient-echo sequence (MPRAGE, 160 slices, 1 mm^3 isotropic voxels) and a gradient-echo MTI (FA 30, TE 15, matrix size 256*256, pixel size 1*1 mm, 36 slices (thickness 2mm), MT pulse duration 7.68 ms, FA 500, frequency offset 1.5 kHz). MTI was performed by acquiring consecutively two set of images; first with and then without the MT saturation pulse. MT images were coregistered to the T1 acquisition. The MTR for every intracranial voxel was calculated as follows: MTR = (M0 - MS)/M0*100%, creating a MTR map for each subject. As first analysis, the whole white matter (WM) was used to mask the MTR image in order to create an histogram of the MTR distribution in the whole tissue class over the two groups examined. Then, for each subject, we performed a segmentation and parcellation of the brain by means of Freesurfer software, starting from the high resolution T1-weighted anatomical acquisition. Cortical parcellations was used to assign a label to the underlying white matter by the construction of a Voronoi diagram in the WM voxels of the MR volume based on distance to the nearest cortical parcellation label. This procedure allowed us to subdivide the cerebral WM in 78 ROIs according to the cortical parcellation (see example in Fig 1). The cerebellum, by the same procedure, was subdivided in 5 ROIs (2 per each hemisphere and one corresponding to the brainstem). For each subject, we calculated the mean value of MTR within each ROI and averaged over controls and patients. Significant differences between the two groups were tested using a two sample T-test (p<0.01). Results: Neurological examination showed that no patient met the clinical criteria of Fragile X Tremor and Ataxia Syndrome yet. Nonetheless, premutation carriers showed some subtle neurological signs of the disorder. In fact, premutation carriers showed a significant increase of tremor (CRST, T-test p=0.007) and increase of ataxia (ICARS, p=0.004) when compared to controls. The neuropsychological evaluation was normal in both groups. To obtain general characterizations of myelination for each subject and premutation carriers, we first computed the distribution of MTR values across the total white matter volume and averaged for each group. We tested the equality of the two distributions with the non parametric Kolmogorov-Smirnov test and we rejected the null-hypothesis at a p=0.03 (fig. 2). As expected, when comparing the asymptomatic permutation carriers with control subjects, the peak value and peak position of the MTR values within the whole WM were decreased and the width of the distribution curve was increased (p<0.01). These three changes point to an alteration of the global myelin status of the premutation carriers. Subsequently, to analyze the regional myelination and white matter integrity of the same group, we performed a ROI analysis of MTR data. The ROI-based analysis showed a decrease of mean MTR value in premutation carriers compared to controls in bilateral orbito-frontal and inferior frontal WM, entorhinal and cingulum regions and cerebellum (Fig 3). The detection of these differences in these regions failed with other conventional MR techniques. Conclusions: These preliminary data confirm that in premutation carriers, there are indeed alterations in "normal appearing white matter" (NAWM) and these alterations are visible with the MT technique. These results indicate that MT imaging may be a relevant approach to detect both global and local alterations within NAWM in "asymptomatic" carriers of premutations in the Fragile X Mental Retardation 1 (FMR1) gene. The sensitivity of MT in the detection of these alterations might point towards a specific physiopathological mechanism linked to an underlying myelin disorder. ROI-based analyses show that the frontal, parahippocampal and cerebellar regions are already significantly affected before the onset of symptoms. A larger sample will allow us to determine the minimum CGG expansion and age associated with these subclinical white matter alterations.

Safety and feasibility of NeuroFlo use in eight- to 24-hour ischemic stroke patients.

BACKGROUND: Acute treatment of ischemic stroke patients presenting more than eight-hours after symptom onset remains limited and largely unproven. Partial aortic occlusion using the NeuroFlo catheter can augment cerebral perfusion in animals. We investigated the safety and feasibility of employing this novel catheter to treat ischemic stroke patients eight-hours to 24 h following symptom onset. METHODS: A multicenter, single-arm trial enrolled ischemic stroke patients at nine international academic medical centers. Eligibility included age 18-85 years old, National Institutes of Health stroke scale (NIHSS) score between four and 20, within eight-hours to 24 h after symptom onset, and perfusion-diffusion mismatch confirmed by magnetic resonance imaging. The primary outcome was all adverse events occurring from baseline to 30 days posttreatment. Secondary outcomes included stroke severity on neurological indices through 90 days. This study is registered with ClinicalTrials.gov, number NCT00436592. RESULTS: A total of 26 patients were enrolled. Of these, 25 received treatment (one excluded due to aortic morphology); five (20%) died. Favorable neurological outcome at 90 days (modified Rankin score 0-2 vs. 3-6) was associated with lower baseline NIHSS (P < 0·001) and with longer duration from symptom discovery to treatment. There were no symptomatic intracranial hemorrhages or parenchymal hematomas. Asymptomatic intracranial hemorrhage was visible on computed tomography in 32% and only on microbleed in another 20%. CONCLUSIONS: Partial aortic occlusion using the NeuroFlo catheter, a novel collateral therapeutic strategy, appears safe and feasible in stroke patients eight-hours to 24 h after symptom onset.

Involvement of central nervous system in the schistosomiasis

The involvement of the central nervous system (CNS) by schistosomes may or may not determine clinical manifestations. When symptomatic, neuroschistosomiasis (NS) is one of the most severe presentations of schistosomal infection. Considering the symptomatic form, cerebral involvement is almost always due to Schistosoma japonicum and the spinal cord disease, caused by S. mansoni or S. haematobium. Available evidence suggests that NS depends basically on the presence of parasite eggs in the nervous tissue and on the host immune response. The patients with cerebral NS usually have the clinical manifestations of increased intracranial pressure associated with focal neurological signs; and those with schistosomal myeloradiculopathy (SMR) present rapidly progressing symptoms of myelitis involving the lower cord, usually in association with the involvement of the cauda esquina roots. The diagnosis of cerebral NS is established by biopsy of the nervous tissue and SMR is usually diagnosed according to a clinical criterion. Antischistosomal drugs, corticosteroids and surgery are the resourses available for treating NS. The outcome is variable and is better in cerebral disease.

Age Related Outcome in Acute Subdural Haematoma Following Traumatic Head Injury

Acute subdural haematoma (ASDH) is one of the conditions most strongly associated with severe brain injury. Reports prior to 1980 describe overall mortality rates for acute subdural haematomas (SDH's) ranging from 40% to 90% with poor outcomes observed in all age groups. Recently, improved results have been reported with rapid diagnosis and surgical treatment. The elderly are predisposed to bleeding due to normal cerebral atrophy related to aging, stretching the bridging veins from the dura. Prognosis in ASDH is associated with age, time from injury to treatment, presence of pupillary abnormalities, Glasgow Coma Score (GCS) or motor score on admission, immediate coma or lucid interval, computerized tomography findings (haematoma volume, degree of midline shift, associated intradural lesion, compression of basal cisterns), post-operative intracranial pressure and type of surgery. Advancing age is known to be a determinant of outcome in head injury. The authors present the results of a retrospective study carried out in Beaumont Hospital, Dublin, Ireland's national neurosurgical centre. The aim of this study was to examine the impact of age on outcome in patients with ASDH following severe head injury. Only cases with acute subdural haematoma requiring surgical evacuation were recruited.

Elevated levels of MIC-1/GDF15 in the cerebrospinal fluid of patients are associated with glioblastoma and worse outcome.

For patients with brain tumors identification of diagnostic and prognostic markers in easy accessible biological material, such as plasma or cerebrospinal fluid (CSF), would greatly facilitate patient management. MIC-1/GDF15 (growth differentiation factor 15) is a secreted protein of the TGF-beta superfamily and emerged as a candidate marker exhibiting increasing mRNA expression during malignant progression of glioma. Determination of MIC-1/GDF15 protein levels by ELISA in the CSF of a cohort of 94 patients with intracranial tumors including gliomas, meningioma and metastasis revealed significantly increased concentrations in glioblastoma patients (median, 229 pg/ml) when compared with control cohort of patients treated for non-neoplastic diseases (median below limit of detection of 156 pg/ml, p < 0.0001, Mann-Whitney test). However, plasma MIC-1/GDF15 levels were not elevated in the matching plasma samples from these patients. Most interestingly, patients with glioblastoma and increased CSF MIC-1/GDF15 had a shorter survival (p = 0.007, log-rank test). In conclusion, MIC-1/GDF15 protein measured in the CSF may have diagnostic and prognostic value in patients with intracranial tumors.