Safety and occlusion rates of surgical treatment of unruptured intracranial aneurysms: a systematic review and meta-analysis of the literature from 1990 to 2011.

BACKGROUND AND PURPOSE: Surgical clipping of unruptured intracranial aneurysms (UIAs) has recently been challenged by the emergence of endovascular treatment. We performed an updated systematic review and meta-analysis on the surgical treatment of UIAs, in an attempt to determine the aneurysm occlusion rates and safety of surgery in the modern era. METHODS: A detailed protocol was developed prior to conducting the review according to the Cochrane Collaboration guidelines. Electronic databases spanning January 1990-April 2011 were searched, complemented by hand searching. Heterogeneity was assessed using I(2), and publication bias with funnel plots. Surgical mortality and morbidity were analysed with weighted random effect models. RESULTS: 60 studies with 9845 patients harbouring 10 845 aneurysms were included. Mortality occurred in 157 patients (1.7%; 99% CI 0.9% to 3.0%; I(2)=82%). Unfavourable outcomes, including death, occurred in 692 patients (6.7%; 99% CI 4.9% to 9.0%; I(2)=85%). Morbidity rates were significantly greater in higher quality studies, and with large or posterior circulation aneurysms. Reported morbidity rates decreased over time. Studies were generally of poor quality; funnel plots showed heterogeneous results and publication bias, and data on aneurysm occlusion rates were scant. CONCLUSIONS: In studies published between 1990 and 2011, clipping of UIAs was associated with 1.7% mortality and 6.7% overall morbidity. The reputed durability of clipping has not been rigorously documented. Due to the quality of the included studies, the available literature cannot properly guide clinical decisions.

Thrombolysis in ischemic stroke without arterial occlusion at presentation.

BACKGROUND AND PURPOSE: None of the randomized trials of intravenous tissue-type plasminogen activator reported vascular imaging acquired before thrombolysis. Efficacy of tissue-type plasminogen activator in stroke without arterial occlusion on vascular imaging remains unknown and speculative. METHODS: We performed a retrospective, multicenter study to collect data of patients who presented to participating centers during a 5-year period with ischemic stroke diagnosed by clinical examination and MRI and with imaging evidence of no vascular occlusion. These patients were divided into 2 groups: those who received thrombolytic therapy and those who did not. Primary outcome measure of the study was excellent clinical outcome defined as modified Rankin Scale of 0 to 1 at 90 days from stroke onset. Secondary outcome measures were good clinical outcome (modified Rankin Scale, 0-2) and perfect outcome (modified Rankin Scale, 0). Safety outcome measures were incidence of symptomatic intracerebral hemorrhage and poor outcome (modified Rankin Scale, 4-6). RESULTS: A total of 256 patients met study criteria, 103 with thrombolysis and 153 without. Logistic regression analysis showed that patients who received thrombolysis had more frequent excellent outcomes with odds ratio of 3.79 (P<0.01). Symptomatic intracerebral hemorrhage was more frequent in thrombolysis group (4.9 versus 0.7%; P=0.04). Thrombolysis led to more frequent excellent outcome in nonlacunar group with odds ratio 4.90 (P<0.01) and more frequent perfect outcome in lacunar group with odds ratio 8.25 (P<0.01). CONCLUSIONS: This study provides crucial data that patients with ischemic stroke who do not have visible arterial occlusion at presentation may benefit from thrombolysis.

Cortical origin of functional recovery in the somatosensory cortex of the adult mouse after thalamic lesion

Résumé L'accident vasculaire cérébral sensoriel pur est un des syndromes lacunaires, dû à l'occlusion de petits vaisseaux cérébraux, souvent dans le cadre d'une lésion intéressant le noyau ventro-caudal du thalamus. Il produit un hémisyndrome sensitif pur, et parfois un syndrome douloureux se développe à distance de l'événement aigu. Afin d'étudier la récupération fonctionnelle dans le cortex somatosensoriel (SI) après une telle lésion dans le thalamus, un modèle de lésion excitotoxique a été développé dans le système somatosensoriel de la souris adulte, caractérisé par la présence de formations cytoarchitectoniques dans SI appelées "tonneaux". Chacun de ces tonneaux correspond à la représentation corticale d'une vibrisse du museau. L'activité métabolique a été mesurée dans SI à différents intervalles après la lésion, à l'aide de déoxyglucose marqué radioactivement. Dans les deux premiers jours suivant celle-ci, l'activité métabolique diminue de manière importante dans toutes les couches corticales, avec une atteinte plus marquée dans la couche IV, principale projection des axones thalamo-corticaux. Une récupération de l'activité métabolique se produit ensuite, d'autant plus marquée que le délai après la lésion est grand. Cette récupération s'observe dans toutes les couches coticales, les couches I et Vb récupérant plus rapidement que les couches II, III, IV, Va et VI. Cinq semaines après la lésion, l'absence des vibrisses correspondant à la partie déafférentée de SI diminue l'activité métabolique corticale de 32% et démontre l'activation par la périphérie de cette partie de l'écorce, malgré la perte des axones thalamo-corticaux provenant du noyau ventro-caudal. Des expériences de traçage rétrograde ont montré une augmentation des projections intracorticales sur la partie déafférentée de l'écorce, en particulier de longue distance, ainsi que des projections interhémisphériques, mais n'ont pas permis de mettre en évidence de nouvelle projection thalamique, indiquant une origine corticale à la récupération fonctionnelle observée. Abstract To study the degree and time course of the functional recovery in the somatosensory cortex (SI) after an excitotoxic lesion in the adult mouse thalamus, metabolic activity was determined in SI at various times points post lesion. Immediately after the lesion, metabolic activity in the thalamically deafferented part of SI was at its lowest value but increased progressively at subsequent time points. This was seen in all cortical layers, however, layers I and Vb recover more rapidly than layers II, III, IV, Va and VI. Removal of the mystacial whiskers corresponding to the deafferented area, 5 weeks after cortical recovery, produced a subsequent 32% drop in metabolic activity, demonstrating peripheral sensory activation of this part of the cortex. Tracing experiments revealed that the deafferented cortex did not receive a novel thalamic input, but cortico-cortical and contralateral barrel cortex projections to this area were reinforced. We conclude that the cortical functional recovery after a thalamic lesion is, at least partially, due to modified cortico-cortical and callosal projections to the deafferented cortical area.

Aneurysms of saphenous vein grafts as late complication of coronary artery bypass surgery: successful exclusion by percutaneous transcatheter embolization.

We report a case of a 71-year-old man with a long coronary artery disease history and two sets of coronary artery bypass grafts. He developed large aortocoronary saphenous vein graft aneurysms in the two grafts from the first set of aortocoronary saphenous venous 20 years later. During the previous 3 years, the aneurysms grew in diameter from 22 to 50 mm. Because of severe renal insufficiency, and in order to avoid jeopardizing the late normal coronary artery bypass grafts by further thoracic surgery, we excluded successfully these altered grafts percutaneously by using 13 coils during the same procedure.

Ectodysplasin A1 promotes placodal cell fate during early morphogenesis of ectodermal appendages.

Organs developing as appendages of the ectoderm are initiated from epithelial thickenings called placodes. Their formation is regulated by interactions between the ectoderm and underlying mesenchyme, and several signalling molecules have been implicated as activators or inhibitors of placode formation. Ectodysplasin (Eda) is a unique signalling molecule in the tumour necrosis factor family that, together with its receptor Edar, is necessary for normal development of ectodermal organs both in humans and mice. We have shown previously that overexpression of the Eda-A1 isoform in transgenic mice stimulates the formation of several ectodermal organs. In the present study, we have analysed the formation and morphology of placodes using in vivo and in vitro models in which both the timing and amount of Eda-A1 applied could be varied. The hair and tooth placodes of K14-Eda-A1 transgenic embryos were enlarged, and extra placodes developed from the dental lamina and mammary line. Exposure of embryonic skin to Eda-A1 recombinant protein in vitro stimulated the growth and fusion of placodes. However, it did not accelerate the initiation of the first wave of hair follicles giving rise to the guard hairs. Hence, the function of Eda-A1 appears to be downstream of the primary inductive signal required for placode initiation during skin patterning. Analysis of BrdU incorporation indicated that the formation of the epithelial thickening in early placodes does not involve increased cell proliferation and also that the positive effect of Eda-A1 on placode expansion is not a result of increased cell proliferation. Taken together, our results suggest that Eda-A1 signalling promotes placodal cell fate during early development of ectodermal organs.

High-resolution spatial mapping of changes in the neurochemical profile after focal ischemia in mice.

After ischemic stroke, the ischemic damage to brain tissue evolves over time and with an uneven spatial distribution. Early irreversible changes occur in the ischemic core, whereas, in the penumbra, which receives more collateral blood flow, the damage is more mild and delayed. A better characterization of the penumbra, irreversibly damaged and healthy tissues is needed to understand the mechanisms involved in tissue death. MRSI is a powerful tool for this task if the scan time can be decreased whilst maintaining high sensitivity. Therefore, we made improvements to a (1) H MRSI protocol to study middle cerebral artery occlusion in mice. The spatial distribution of changes in the neurochemical profile was investigated, with an effective spatial resolution of 1.4 μL, applying the protocol on a 14.1-T magnet. The acquired maps included the difficult-to-separate glutamate and glutamine resonances and, to our knowledge, the first mapping of metabolites γ-aminobutyric acid and glutathione in vivo, within a metabolite measurement time of 45 min. The maps were in excellent agreement with findings from single-voxel spectroscopy and offer spatial information at a scan time acceptable for most animal models. The metabolites measured differed with respect to the temporal evolution of their concentrations and the localization of these changes. Specifically, lactate and N-acetylaspartate concentration changes largely overlapped with the T(2) -hyperintense region visualized with MRI, whereas changes in cholines and glutathione affected the entire middle cerebral artery territory. Glutamine maps showed elevated levels in the ischemic striatum until 8 h after reperfusion, and until 24 h in cortical tissue, indicating differences in excitotoxic effects and secondary energy failure in these tissue types. Copyright © 2011 John Wiley & Sons, Ltd.

Volvulus de l'intestin grêle comme cause primaire d'abdomen aigu [Volvulus of the small intestine as a cause of primary acute abdomen].

As a cause of small intestine occlusion, volvulus is often a consequence of a band or adhesions. Except in infants, it is rarely the primary cause of symptomatology. Between January 1976 and December 1992, 13 patients (7 women and 6 men, mean age of 56.8 years) were admitted in our department for an acute abdomen due to a spontaneous primary volvulus of the small bowel. Clinical examination and laboratory tests did not help in preoperative diagnosis. All patients underwent an explorative laparotomy. Six patients had had prior abdominal surgery but none of them presented adhesion or band. In 8 patients (62%), detorsion was sufficient. Resection of a segment of small bowel was necessary in 4 patients. Gangrenous of the entire bowel was observed in one patient who rapidly died. Two patients presented minor complications. One patient with Down syndrome died of bronchoaspiration. One patient has been reoperated on one year later for recurrence of the volvulus, and underwent a Noble procedure. We conclude that volvulus of the small bowel is a rare cause of acute abdomen that must be remembered. Early surgery is mandatory to reduce the risk of gangrene, which is known to double the mortality. Laparoscopy will be helpful in early diagnosis and therapy.

Correlation of wear in vivo and six laboratory wear methods.

OBJECTIVE: We examined the correlation between clinical wear rates of restorative materials and enamel (TRAC Research Foundation, Provo, USA) and the results of six laboratory test methods (ACTA, Alabama (generalized, localized), Ivoclar (vertical, volumetric), Munich, OHSU (abrasion, attrition), Zurich). METHODS: Individual clinical wear data were available from clinical trials that were conducted by TRAC Research Foundation (formerly CRA) together with general practitioners. For each of the n=28 materials (21 composite resins for intra-coronal restorations [20 direct and 1 indirect], 5 resin materials for crowns, 1 amalgam, enamel) a minimum of 30 restorations had been placed in posterior teeth, mainly molars. The recall intervals were up to 5 years with the majority of materials (n=27) being monitored, however, only for up to 2 years. For the laboratory data, the databases MEDLINE and IADR abstracts were searched for wear data on materials which were also clinically tested by TRAC Research Foundation. Only those data for which the same test parameters (e.g. number of cycles, loading force, type of antagonist) had been published were included in the study. A different quantity of data was available for each laboratory method: Ivoclar (n=22), Zurich (n=20), Alabama (n=17), OHSU and ACTA (n=12), Munich (n=7). The clinical results were summed up in an index and a linear mixed model was fitted to the log wear measurements including the following factors: material, time (0.5, 1, 2 and 3 years), tooth (premolar/molar) and gender (male/female) as fixed effects, and patient as random effect. Relative ranks were created for each material and method; the same was performed with the clinical results. RESULTS: The mean age of the subjects was 40 (±12) years. The materials had been mostly applied in molars (81%) and 95% of the intracoronal restorations were Class II restorations. The mean number of individual wear data per material was 25 (range 14-42). The mean coefficient of variation of clinical wear data was 53%. The only significant correlation was reached by OHSU (abrasion) with a Spearman r of 0.86 (p=0.001). Zurich, ACTA, Alabama generalized wear and Ivoclar (volume) had correlation coefficients between 0.3 and 0.4. For Zurich, Alabama generalized wear and Munich, the correlation coefficient improved if only composites for direct use were taken into consideration. The combination of different laboratory methods did not significantly improve the correlation. SIGNIFICANCE: The clinical wear of composite resins is mainly dependent on differences between patients and less on the differences between materials. Laboratory methods to test conventional resins for wear are therefore less important, especially since most of them do not reflect the clinical wear.

Ischemic heart disease in postmortem CT and CT angiography

Objective: Postmortem radiology had in recent years appeared in the field of forensic medicine and is now considered by some authors as a good replacement for conventional autopsy and by others as a complementary examination. Although postmortem CT radiological imaging is very useful in demonstrating traumatic lesions, its utility is still quite limited in the cardiovascular field. This limitation could be minimized by the introduction of postmortem angiography. At the University Center of Legal Medicine of Lausanne, CT scans and postmortem multiphase CTangiography are used in cases with a suspicion of ischemic heart disease.Method: The goal of this presentation is to demonstrate some correlations between postmortem CT, CTangiography and conventional autopsy examination in cases of ischemic heart disease.Results: We observed that the native CT scan can show only some pathological findings as cardiac tamponade and calcifications of coronary arteries. However, postmortem angiography allows a better visualization of coronary arteries and evaluation of stenosis and occlusion as well as better imaging of soft tissue.Conclusion: The interpretation of postmortem modern radiology is a new field for both forensic pathologists and radiologists who have to learn to read the postmortem modified images. The information obtained from both parties can help to further the understanding of CT and CT angiography in postmortem cases.

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.

Asymptomatic high flow subclavian steal in a patient with hemodialysis access.

Subclavian steal phenomenon due to proximal subclavian artery stenosis or occlusion is not un-common but often remains asymptomatic. We describe the case of a 66-year-old man with end-stage renal disease hemodialysed through a brachio-brachial loop graft of the left forearm. Echo-Doppler precerebral examination showed a high reversed flow of 570 ml/min in the ipsilateral vertebral artery. After successful endovascular recanalization of the subclavian artery, access blood flow increased and vertebral flow decreased to 30 ml/min. Complete neurological examination was normal both before and after endovascular treatment. This case demonstrates how high a subclavian steal can be without causing symptoms and how well precerbral and cerebral circulation can adapt to hemodynamic changes.

Molecular and therapeutic characterization of anti-ectodysplasin A receptor (EDAR) agonist monoclonal antibodies.

The TNF family ligand ectodysplasin A (EDA) and its receptor EDAR are required for proper development of skin appendages such as hair, teeth, and eccrine sweat glands. Loss of function mutations in the Eda gene cause X-linked hypohidrotic ectodermal dysplasia (XLHED), a condition that can be ameliorated in mice and dogs by timely administration of recombinant EDA. In this study, several agonist anti-EDAR monoclonal antibodies were generated that cross-react with the extracellular domains of human, dog, rat, mouse, and chicken EDAR. Their half-life in adult mice was about 11 days. They induced tail hair and sweat gland formation when administered to newborn EDA-deficient Tabby mice, with an EC(50) of 0.1 to 0.7 mg/kg. Divalency was necessary and sufficient for this therapeutic activity. Only some antibodies were also agonists in an in vitro surrogate activity assay based on the activation of the apoptotic Fas pathway. Activity in this assay correlated with small dissociation constants. When administered in utero in mice or at birth in dogs, agonist antibodies reverted several ectodermal dysplasia features, including tooth morphology. These antibodies are therefore predicted to efficiently trigger EDAR signaling in many vertebrate species and will be particularly suited for long term treatments.

Ectodysplasin A (EDA) - EDA receptor signalling and its pharmacological modulation.

The TNF family ligand ectodysplasin A (EDA) regulates the induction, morphogenesis and/or maintenance of skin-derived structures such as teeth, hair, sweat glands and several other glands. Deficiencies in the EDA - EDA receptor (EDAR) signalling pathway cause hypohidrotic ectodermal dysplasia (HED). This syndrome is characterized by the absence or malformation of several skin-derived appendages resulting in hypotrychosis, hypodontia, heat-intolerance, dry skin and dry eyes, susceptibility to airways infections and crusting of various secretions. The EDA-EDAR system is an important effector of canonical Wnt signalling in developing skin appendages. It functions by stimulating NF-κB-mediated transcription of effectors or inhibitors of the Wnt, Sonic hedgehog (SHH), fibroblast growth factor (FGF) and transforming growth factor beta (TGFβ) pathways that regulate interactions within or between epithelial and mesenchymal cells and tissues. In animal models of Eda-deficiency, soluble EDAR agonists can precisely correct clinically relevant symptoms with low side effects even at high agonist doses, indicating that efficient negative feedback signals occur in treated tissues. Hijacking of the placental antibody transport system can help deliver active molecules to developing foetuses in a timely manner. EDAR agonists may serve to treat certain forms of ectodermal dysplasia.

Percutaneous Endovascular Salvage Techniques for Implanted Venous Access Device Dysfunction.

PURPOSE: Implanted venous access devices (IVADs) are often used in patients who require long-term intravenous drug administration. The most common causes of device dysfunction include occlusion by fibrin sheath and/or catheter adherence to the vessel wall. We present percutaneous endovascular salvage techniques to restore function in occluded catheters. The aim of this study was to evaluate the feasibility, safety, and efficacy of these techniques. METHODS AND MATERIALS: Through a femoral or brachial venous access, a snare is used to remove fibrin sheath around the IVAD catheter tip. If device dysfunction is caused by catheter adherences to the vessel wall, a new "mechanical adhesiolysis" maneuver was performed. IVAD salvage procedures performed between 2005 and 2013 were analyzed. Data included clinical background, catheter tip position, success rate, recurrence, and rate of complication. RESULTS: Eighty-eight salvage procedures were performed in 80 patients, mostly women (52.5 %), with a mean age of 54 years. Only a minority (17.5 %) of evaluated catheters were located at an optimal position (i.e., cavoatrial junction ±1 cm). Mechanical adhesiolysis or other additional maneuvers were used in 21 cases (24 %). Overall technical success rate was 93.2 %. Malposition and/or vessel wall adherences were the main cause of technical failure. No complications were noted. CONCLUSION: These IVAD salvage techniques are safe and efficient. When a catheter is adherent to the vessel wall, mechanical adhesiolysis maneuvers allow catheter mobilization and a greater success rate with no additional risk. In patients who still require long-term use of their IVAD, these procedures can be performed safely to avoid catheter replacement.