Marco Antonio Stefani

Medical management with or without interventional therapy for unruptured brain arteriovenous malformations (ARUBA): a multicentre, non-blinded, randomised trial.

BACKGROUND The clinical benefit of preventive eradication of unruptured brain arteriovenous malformations remains uncertain. A Randomised trial of Unruptured Brain Arteriovenous malformations (ARUBA) aims to compare the risk of death and symptomatic stroke in patients with an unruptured brain arteriovenous malformation who are allocated to either medical management alone or medical management with interventional therapy. METHODS Adult patients (≥18 years) with an unruptured brain arteriovenous malformation were enrolled into this trial at 39 clinical sites in nine countries. Patients were randomised (by web-based system, in a 1:1 ratio, with random permuted block design [block size 2, 4, or 6], stratified by clinical site) to medical management with interventional therapy (ie, neurosurgery, embolisation, or stereotactic radiotherapy, alone or in combination) or medical management alone (ie, pharmacological therapy for neurological symptoms as needed). Patients, clinicians, and investigators are aware of treatment assignment. The primary outcome is time to the composite endpoint of death or symptomatic stroke; the primary analysis is by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00389181. FINDINGS Randomisation was started on April 4, 2007, and was stopped on April 15, 2013, when a data and safety monitoring board appointed by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health recommended halting randomisation because of superiority of the medical management group (log-rank Z statistic of 4·10, exceeding the prespecified stopping boundary value of 2·87). At this point, outcome data were available for 223 patients (mean follow-up 33·3 months [SD 19·7]), 114 assigned to interventional therapy and 109 to medical management. The primary endpoint had been reached by 11 (10·1%) patients in the medical management group compared with 35 (30·7%) in the interventional therapy group. The risk of death or stroke was significantly lower in the medical management group than in the interventional therapy group (hazard ratio 0·27, 95% CI 0·14-0·54). No harms were identified, other than a higher number of strokes (45 vs 12, p<0·0001) and neurological deficits unrelated to stroke (14 vs 1, p=0·0008) in patients allocated to interventional therapy compared with medical management. INTERPRETATION The ARUBA trial showed that medical management alone is superior to medical management with interventional therapy for the prevention of death or stroke in patients with unruptured brain arteriovenous malformations followed up for 33 months. The trial is continuing its observational phase to establish whether the disparities will persist over an additional 5 years of follow-up. FUNDING National Institutes of Health, National Institute of Neurological Disorders and Stroke.

Neuron-Specific Enolase, S100B, and Glial Fibrillary Acidic Protein Levels as Outcome Predictors in Patients With Severe Traumatic Brain Injury

BACKGROUND:The availability of markers able to provide an early insight related to prognostic and functional outcome of patients with traumatic brain injury (TBI) are limited. OBJECTIVE:The relationship of clinical outcome with CSF neuron-specific enolase (NSE), S100B and glial fibrillary acidic protein (GFAP) levels in patients with severe TBI was investigated. METHODS:Twenty patients with severe TBI (7 days at unit care) and controls were studied. Patients were grouped according to the outcome: (1) nonsurvival (n = 5): patients who died; (2) survival A (n = 15): CSF sampled between 1st and 3rd day from patients who survived after hospital admission; and (3) survival B (n = 7): CSF sampled between 4th and 7th day from patients who survived after hospital admission and were maintained with intraventricular catheter up to 7 days. RESULTS:Up to 3 days, S100B and NSE levels (ng/mL) were significantly elevated in the nonsurvival compared with survival A group (S100: 12.45 ± 5.46 vs 5.64 ± 3.36; NSE: 313.20 ± 45.51 vs 107.80 ± 112.10). GFAP levels did not differ between groups. In the survival B group S100B, GFAP, and NSE levels were still elevated compared with control (4.59 ± 2.19, 2.48 ± 2.55, and 89.80 ± 131.10, respectively). To compare S100B and NSE for the prediction of nonsurvival and survival patients we performed receiver operating characteristic curves. At admission, CSF NSE level predicts brain death more accurately than S100B. CONCLUSION:Early elevations (up to 3 days) of S100B and NSE secondary to severe TBI predict deterioration to brain death. However, this feature was more prominently associated with NSE than S100B.

A Morphometric Study of the Larynx

OBJECTIVE Describe anatomical measurements of a selection of laryngeal structures, performing a comparison of such measurements between men and women and between different age groups. STUDY DESIGN Populational morphometric study. PARTICIPANTS Larynges from 50 male and 50 female fresh cadavers of older than 40 years were removed during autopsy. METHODS The following measurements were made on the external angle laryngeal framework between the blades of the thyroid cartilage: width of the thyroid cartilage, distance from the thyroid notch to the anterior commissure (AC), distance from the AC to the inferior thyroid border, distance from the AC to the larynx proeminence, length of membranacea part of vocal fold (VF), length of cartilaginea part of VF, width and thickness of true VF. RESULTS The differences between men and women were highly significant. All measured values of larynx obtained in the study were greater in men than in women, except for the thyroid angle, which was higher in women (P < 0.05). A significant difference in the comparison between the morphological measurements in the age groups for both men and women was not observed (P > 0.05). CONCLUSION The comparison of larynx dimensions showed the presence of sexual dimorphism in the group of South Brazilian people studied. There was no morphometric difference between the larynx samples of the individuals of the same sex after 40 years of age.

Acute Normovolemic Hemodilution Is Safe in Neurosurgery

OBJECTIVE To determine the safety of acute normovolemic hemodilution (ANH) for patients undergoing neurosurgical procedures. METHODS A group of 100 patients undergoing neurosurgical procedures was assigned prospectively to receive ANH. A group of 47 patients who underwent craniotomy for aneurysm clipping and standard anesthetic management was used as a control. Procedures conducted under ANH were performed without significant variations in physiologic parameters. RESULTS Compared with controls, intraoperative blood loss, operative time, incidence and grade of complications, and length of hospital stay were similar between the two groups. Although the ANH group showed a difference in prothrombin levels before and after hemodilution procedures, the levels were still considered within physiologic parameters. Platelet counts and partial thromboplastin time (PTT) levels indicated no significant variations in either group. During the ANH procedure, a considerable reduction of brain oxygen extraction was observed in individuals with worse preoperative neurologic status (P < 0.05), indicating potential benefit. Among patients with cerebral aneurysm, patients with good initial clinical grades had better clinical results as indicated by Glasgow Outcome Scale scores (P < 0.02). CONCLUSIONS ANH is a safe procedure for patients undergoing neurosurgical procedures. Further studies are necessary to confirm the improvement in brain oxygen extraction and the clinical impact. Nonetheless, patients undergoing aneurysm clipping with good clinical grades seem to profit from ANH.

Elevated glutamate and lactate predict brain death after severe head trauma

Clinical neurological assessment is challenging for severe traumatic brain injury (TBI) patients in the acute setting. Waves of neurochemical abnormalities that follow TBI may serve as fluid biomarkers of neurological status. We assessed the cerebrospinal fluid (CSF) levels of glutamate, lactate, BDNF, and GDNF, to identify potential prognostic biomarkers of neurological outcome.

The hidden symbols of the female anatomy in Michelangelo Buonarroti's ceiling in the Sistine Chapel

A number of published articles have suggested that each element of Renaissance art contains an inner meaning. Some of these elements include the choice of theme and protagonists, faces selected for the characters, colors used, species of flowers and trees chosen, animals depicted, positions of the elements, posture of the characters and their gestures, juxtapositions in the scenes, and even the very scenario or landscape. All of these elements are thought to have hidden meanings. In this context, this manuscript presents a new hypothesis suggesting that Michelangelo Buonarroti (1475–1564) may have concealed symbols associated with female anatomy in the ceiling of the Sistine Chapel (painted 1508–1512) in Rome. Thus, this paper is useful to better understand the history of anatomy and corroborates recent descriptions that have suggested the possible existence of anatomic figures concealed in many of Michelangelos works. Clin. Anat. 29:911–916, 2016.

Prevalência de dor osteomuscular em profissionais de enfermagem de equipes de cirurgia em um hospital universitário

Dentre as profissoes da area da saude, a enfermagem, em particular, tem sido afetada pelos disturbios musculoesqueleticos produzindo alteracoes na vida desses trabalhadores, impossibilitando-os de realizarem atividades cotidianas e laborais. Objetivo: Investigar a prevalencia de dor osteomuscular e a associacao com a qualidade de vida em profissionais de enfermagem que atuam em equipes de cirurgia no Hospital de Clinicas de Porto Alegre. Metodo: Estudo transversal realizado entre marco de 2011 e janeiro de 2012, em um hospital universitario terciario do sul do Brasil. Foram avaliados 110 trabalhadores de enfermagem das equipes de cirurgia. Foram excluidos os trabalhadores em licenca saude, ferias ou outro tipo de afastamento durante o periodo de coleta dos dados. A dor osteomuscular foi avaliada atraves do questionario Nordico de Sintomas Osteomusculares e a qualidade de vida foi avaliada atraves do questionario Medical Outcomes Study 36 - Item Short-Form Survey (SF-36). As relacoes entre dor osteomuscular e qualidade de vida foram analisadas atraves do Teste U de Mann-Whitney, utilizando nivel de significância de 95%. Resultados: A prevalencia de dor osteomuscular encontrada neste estudo foi de 91,81%. Com relacao as regioes anatomicas, considerou-se as queixas de dor osteomuscular retroativo ha doze meses, onde o predominio foi de dor no pescoco (56%) e ombros (56%). Quando consideramos afastamento por dor osteomuscular encontramos a prevalencia de dor lombar (34%). O grupo que nao relatou dor osteomuscular apresentou melhores indices de qualidade de vida nos dominios de capacidade funcional, aspectos fisicos, dor, vitalidade, aspectos sociais e saude mental. Conclusao: A dor osteomuscular apresenta maior prevalencia nas regioes do pescoco e ombros. Alem disso, o maior numero de afastamentos ocorre por prevalencia de dor lombar entre os trabalhadores de enfermagem das equipes de cirurgia. A dor influenciou na qualidade de vida afetando seis dos dominios avaliados.

Functional impairments for outcomes in a randomized trial of unruptured brain AVMs

Objective: To investigate the effects of medical vs interventional management on functional outcome in A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA). Methods: We used the initial results of a nonblinded, randomized, controlled, parallel-group trial involving adults ≥18 years of age with an unruptured brain arteriovenous malformation (AVM) to compare the effects of medical management (MM) with or without interventional therapy (IT) on functional impairment, defined by a primary outcome of death or symptomatic stroke causing modified Rankin Scale (mRS) score ≥2. ARUBA closed recruitment on April 15, 2013. Results: After a median of 33.3 months of follow-up (interquartile range 16.3–49.8 months), of the 223 enrolled in the trial, those in the MM arm were less likely to experience primary outcomes with an mRS score ≥2 than those who underwent IT. The results applied for both those as randomized (MM n = 109 vs IT n = 114) (hazard ratio [HR] 0.25, 95% confidence interval [CI] 0.11–0.57, p = 0.001) and as treated (MM n = 125 vs IT n = 98) (HR 0.10, 95% CI 0.04–0.28, p < 0.001). Functional impairment for the outcomes showed no significant difference by Spetzler-Martin grade for MM but was more frequent with increasing grades for IT (p < 0.001). Conclusion: Death or stroke with functional impairment in ARUBA after a median follow-up of 33 months was significantly lower for those in the MM arm both as randomized and as treated compared with those with IT. Functional severity of outcomes was lower in the MM arm, regardless of Spetzler-Martin grades. ClinicalTrials.gov identifier: NCT00389181. Classification of evidence: This study provides Class II evidence that for adults with unruptured brain AVMs, interventional management compared to MM increases the risk of disability and death over ≈3 years.

Prospective factors of temporary arterial occlusion during anterior communicating artery aneurysm repair.

INTRODUCTION This study was undertaken to determine variables that could predict, in the perioperative period of anterior communicating artery (ACom) aneurysms surgeries, the likelihood of postoperative sequelae and complications, after temporary arterial occlusion (TAO). PATIENTS AND METHODS In a universe of 32 patients submitted to ACom aneurysm repair in the last 7 years, 21 needed TAO intraoperatively, and had their data examined retrospectively. RESULTS Aneurysms larger than 7 mm were more likely to be treated with longer TAO time than small aneurysms, (p < 0.0001). There was no statistical correlation between time of occlusion and outcome. Age, Glasgow Coma Scale at initial evaluation, and Fisher scale at first CT scanning were independent factors of unfavorable outcome (p < 0.001). Meanwhile gender, tobacco addiction, obesity, arterial hypertension, dyslipidemia, location of TAO (A1 or A2), intraoperative rupture (IR) and the aneurysm size were not identified as independent prognostic factors.During follow-up period, two thirds of the patients had a favorable outcome, accomplishing normal daily life activities without major complications. Most patients developed clinical vasospasm (66.6 %), with 19 % of the patients harboring a severe disease. Delayed ischemic neurological deficit was observed in 28.5 %, without any statistical correlation to time of TAO or IR. CONCLUSION TAO during ACom aneurysm repair does not seem to add more morbidities to the procedure, and is not an independent prognostic factor.

Replication Study of Polymorphisms Associated With Brain Arteriovenous Malformation in a Population From South of Brazil.

Introduction The aim of this study was to reproducibly determine if any of the polymorphisms were associated with the susceptibility to brain arteriovenous malformations (BAVM) or the risk of intracranial hemorrhage (ICH) presentation. Methods We recruited 63 BAVM patients and 96 controls. The polymorphisms selected for evaluation were apolipoprotein E (APOE), tumor necrosis factor alpha (TNF 238G>A - rs361525), interleukin 1 beta (IL1B 511C>T - rs16944 and IL1B -31T>C - rs1143627), activin-like kinase 1 (ACVRL1 IVS3-35A>G - rs2071219), endoglin (ENG 207G>A - rs11545664), and interleukin 6 (IL6 174G>C - rs1800795). Results In the single analysis, we observed statistically significant differences in the allele distributions for IL1B -31T>C (rs1143627) between the BAVM patients and control subjects (P = 0.02). There was a trend toward significance for the association between the IL1B 511C>T (rs16944) allele and BAVM risk (P = 0.07). In further logistic regression analysis, no polymorphism was significantly associated with the risk of BAVM. No polymorphisms were associated with hemorrhage presentation according to both single and multivariable analyses. Conclusions In our sample from a south Brazil population, we found no association between the risks of BAVM and ICH presentation with any of the selected polymorphisms.