Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke.

BACKGROUND: Intravenous infusion of alteplase is used for thrombolysis before endovascular thrombectomy for ischemic stroke. Tenecteplase, which is more fibrin-specific and has longer activity than alteplase, is given as a bolus and may increase the incidence of vascular reperfusion. METHODS: We randomly assigned patients with ischemic stroke who had occlusion of the internal carotid, basilar, or middle cerebral artery and who were eligible to undergo thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or alteplase (at a dose of 0.9 mg per kilogram; maximum dose, 90 mg) within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the time of the initial angiographic assessment. Noninferiority of tenecteplase was tested, followed by superiority. Secondary outcomes included the modified Rankin scale score (on a scale from 0 [no neurologic deficit] to 6 [death]) at 90 days. Safety outcomes were death and symptomatic intracerebral hemorrhage. RESULTS: Of 202 patients enrolled, 101 were assigned to receive tenecteplase and 101 to receive alteplase. The primary outcome occurred in 22% of the patients treated with tenecteplase versus 10% of those treated with alteplase (incidence difference, 12 percentage points; 95% confidence interval [CI], 2 to 21; incidence ratio, 2.2; 95% CI, 1.1 to 4.4; P=0.002 for noninferiority; P=0.03 for superiority). Tenecteplase resulted in a better 90-day functional outcome than alteplase (median modified Rankin scale score, 2 vs. 3; common odds ratio, 1.7; 95% CI, 1.0 to 2.8; P=0.04). Symptomatic intracerebral hemorrhage occurred in 1% of the patients in each group. CONCLUSIONS: Tenecteplase before thrombectomy was associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset. (Funded by the National Health and Medical Research Council of Australia and others; EXTEND-IA TNK ClinicalTrials.gov number, NCT02388061 .).

Association between CYP2C9 polymorphisms and ischemic stroke following endovascular neurointervention.

OBJECTIVE: Polymorphisms in the CYP2C9 gene may be associated with adverse vascular events following endovascular procedures independent of antiplatelet therapy. We aimed to investigate the impact of CYP2C9 loss-of-function polymorphisms on adverse vascular events following neurointervention. PATIENTS AND METHODS: Consecutive patients undergoing neurointervention were prospectively recruited between 2010 and 2016. Patients were genotyped for the CYP2C9*2 and *3 loss-of-function polymorphisms. On the basis of possible genetic influence on antiplatelet response, ex vivo clopidogrel response was measured using the VerifyNow® P2Y12 Assay. The primary endpoint was the 90-day incidence of adverse vascular events including ischemic stroke. RESULTS: A total of 229 patients were included. The median age was 57 years (IQR: 49-64), and 158 (69.00%) were female. Eighty-one (35.37%) patients carried at least one CYP2C9 loss-of-function (LOF) allele. After adjustment for stroke risk factors, the 90-day incidence of ischemic stroke was significantly lower in the LOF group compared to the wild type group (1.23% vs 10.14%; ORadj = 0.16, 95% CI: 0.03-0.91; p = 0.04). CONCLUSIONS: Our results suggest protection against ischemic stroke in carriers of CYP2C9*2 or *3 polymorphisms undergoing neurointervention. Our findings warrant further studies to investigate the mechanisms by which CYP2C9 may influence the risk of ischemic stroke.

Standards of Practice in Acute Ischemic Stroke Intervention International Recommendations.

After five positive randomized controlled trials showed benefit of mechanical thrombectomy in the management of acute ischemic stroke with emergent large-vessel occlusion, a multi-society meeting was organized during the 17th Congress of the World Federation of Interventional and Therapeutic Neuroradiology in October 2017 in Budapest, Hungary. This multi-society meeting was dedicated to establish standards of practice in acute ischemic stroke intervention aiming for a consensus on the minimum requirements for centers providing such treatment. In an ideal situation, all patients would be treated at a center offering a full spectrum of neuroendovascular care (a level 1 center). However, for geographical reasons, some patients are unable to reach such a center in a reasonable period of time. With this in mind, the group paid special attention to define recommendations on the prerequisites of organizing stroke centers providing medical thrombectomy for acute ischemic stroke, but not for other neurovascular diseases (level 2 centers). Finally, some centers will have a stroke unit and offer intravenous thrombolysis, but not any endovascular stroke therapy (level 3 centers). Together, these level 1, 2, and 3 centers form a complete stroke system of care. The multi-society group provides recommendations and a framework for the development of medical thrombectomy services worldwide.

Incidence and prevalence of NMOSD in Australia and New Zealand.

OBJECTIVES: We have undertaken a clinic-based survey of neuromyelitis optica spectrum disorders (NMOSDs) in Australia and New Zealand to establish incidence and prevalence across the region and in populations of differing ancestry. BACKGROUND: NMOSD is a recently defined demyelinating disease of the central nervous system (CNS). The incidence and prevalence of NMOSD in Australia and New Zealand has not been established. METHODS: Centres managing patients with demyelinating disease of the CNS across Australia and New Zealand reported patients with clinical and laboratory features that were suspicious for NMOSD. Testing for aquaporin 4 antibodies was undertaken in all suspected cases. From this group, cases were identified who fulfilled the 2015 Wingerchuk diagnostic criteria for NMOSD. A capture-recapture methodology was used to estimate incidence and prevalence, based on additional laboratory identified cases. RESULTS: NMOSD was confirmed in 81/170 (48%) cases referred. Capture-recapture analysis gave an adjusted incidence estimate of 0.37 (95% CI 0.35 to 0.39) per million per year and a prevalence estimate for NMOSD of 0.70 (95% CI 0.61 to 0.78) per 100 000. NMOSD was three times more common in the Asian population (1.57 (95% CI 1.15 to 1.98) per 100 000) compared with the remainder of the population (0.57 (95% CI 0.50 to 0.65) per 100 000). The latitudinal gradient evident in multiple sclerosis was not seen in NMOSD. CONCLUSIONS: NMOSD incidence and prevalence in Australia and New Zealand are comparable with figures from other populations of largely European ancestry. We found NMOSD to be more common in the population with Asian ancestry.

PPREMO: a prospective cohort study of preterm infant brain structure and function to predict neurodevelopmental outcome.

BACKGROUND: More than 50 percent of all infants born very preterm will experience significant motor and cognitive impairment. Provision of early intervention is dependent upon accurate, early identification of infants at risk of adverse outcomes. Magnetic resonance imaging at term equivalent age combined with General Movements assessment at 12 weeks corrected age is currently the most accurate method for early prediction of cerebral palsy at 12 months corrected age. To date no studies have compared the use of earlier magnetic resonance imaging combined with neuromotor and neurobehavioural assessments (at 30 weeks postmenstrual age) to predict later motor and neurodevelopmental outcomes including cerebral palsy (at 12-24 months corrected age). This study aims to investigate i) the relationship between earlier brain imaging and neuromotor/neurobehavioural assessments at 30 and 40 weeks postmenstrual age, and ii) their ability to predict motor and neurodevelopmental outcomes at 3 and 12 months corrected age. METHODS/DESIGN: This prospective cohort study will recruit 80 preterm infants born ≤ 30 week's gestation and a reference group of 20 healthy term born infants from the Royal Brisbane & Women's Hospital in Brisbane, Australia. Infants will undergo brain magnetic resonance imaging at approximately 30 and 40 weeks postmenstrual age to develop our understanding of very early brain structure at 30 weeks and maturation that occurs between 30 and 40 weeks postmenstrual age. A combination of neurological (Hammersmith Neonatal Neurologic Examination), neuromotor (General Movements, Test of Infant Motor Performance), neurobehavioural (NICU Network Neurobehavioural Scale, Premie-Neuro) and visual assessments will be performed at 30 and 40 weeks postmenstrual age to improve our understanding of the relationship between brain structure and function. These data will be compared to motor assessments at 12 weeks corrected age and motor and neurodevelopmental outcomes at 12 months corrected age (neurological assessment by paediatrician, Bayley scales of Infant and Toddler Development, Alberta Infant Motor Scale, Neurosensory Motor Developmental Assessment) to differentiate atypical development (including cerebral palsy and/or motor delay). DISCUSSION: Earlier identification of those very preterm infants at risk of adverse neurodevelopmental and motor outcomes provides an additional period for intervention to optimise outcomes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12613000280707. Registered 8 March 2013.

Distance informed Track-Weighted Imaging (diTWI): a framework for sensitising streamline information to neuropathology.

Track-Weighted Imaging (TWI), where voxel intensity is based on image metrics encoded along streamline trajectories, provides a mechanism to study white matter disease. However, with generalised streamline weighting, it is difficult to localise the precise anatomical source and spread of injury or neuropathology. This limitation can be overcome by modulating the voxel weight based on the distance of the voxel from a given anatomical location along the tract, which we term diTWI: distance informed Track-Weighted Imaging. The location of known neuropathology can be delineated on any given imaging modality (e.g. MRI or PET). To demonstrate the clinical utility of this approach, we measured tumour cell infiltration along WM fibre tracts in 13 patients with newly diagnosed glioblastoma and 1 patient with Anaplastic Astrocytoma. TWI and diTWI maps were generated using information obtained from dynamic contrast enhanced MRI (area under the curve, AUC) and diffusivity maps (ADC and FA) with tumour boundaries automatically extracted using a logistic regression classifier. The accuracy of the derived tumour volumes was compared to those generated using 3,4-dihydroxy-6-[(18)F]-fluoro-l-phenylalanine (FDOPA) PET imaging. The accuracy of the tumour volumes generated from the diTWI maps was superior to volumes derived from the TWI, geometric distance or baseline AUC, FA and ADC maps. The relative overlap and relative dissimilarity rates for the diTWI generated tumour volumes after classification were found to be 82.3±15.3% (range 69.1-91.9) and 16.9±8.8% (range 7.9-37.5), respectively. These findings show that diTWI maps provide a useful framework for localising neuropathological processes occurring along WM pathways.

Epstein-Barr virus-specific adoptive immunotherapy for progressive multiple sclerosis.

Defective control of Epstein-Barr virus (EBV) infection by cytotoxic CD8(+) T cells might predispose to multiple sclerosis (MS) by allowing EBV-infected autoreactive B cells to accumulate in the central nervous system. We have treated a patient with secondary progressive MS with in vitro-expanded autologous EBV-specific CD8(+) T cells directed against viral latent proteins. This adoptive immunotherapy had no adverse effects and the patient showed clinical improvement with reduced disease activity on magnetic resonance imaging and decreased intrathecal immunoglobulin production. This is the first report of the use of EBV-specific adoptive immunotherapy to treat MS or any other autoimmune disease.

Magnetic resonance imaging: an accurate, radiation-free, alternative to computed tomography for the primary imaging and three-dimensional reconstruction of the bony orbit.

PURPOSE: To determine the extent to which the accuracy of magnetic resonance imaging (MRI) based virtual 3-dimensional (3D) models of the intact orbit can approach that of the gold standard, computed tomography (CT) based models. The goal was to determine whether MRI is a viable alternative to CT scans in patients with isolated orbital fractures and penetrating eye injuries, pediatric patients, and patients requiring multiple scans in whom radiation exposure is ideally limited. MATERIALS AND METHODS: Patients who presented with unilateral orbital fractures to the Royal Brisbane and Women's Hospital from March 2011 to March 2012 were recruited to participate in this cross-sectional study. The primary predictor variable was the imaging technique (MRI vs CT). The outcome measurements were orbital volume (primary outcome) and geometric intraorbital surface deviations (secondary outcome) between the MRI- and CT-based 3D models. RESULTS: Eleven subjects (9 male) were enrolled. The patients' mean age was 30 years. On average, the MRI models underestimated the orbital volume of the CT models by 0.50 ± 0.19 cm(3). The average intraorbital surface deviation between the MRI and CT models was 0.34 ± 0.32 mm, with 78 ± 2.7% of the surface within a tolerance of ±0.5 mm. CONCLUSIONS: The volumetric differences of the MRI models are comparable to reported results from CT models. The intraorbital MRI surface deviations are smaller than the accepted tolerance for orbital surgical reconstructions. Therefore, the authors believe that MRI is an accurate radiation-free alternative to CT for the primary imaging and 3D reconstruction of the bony orbit.

Correlation of adrenomedullin gene expression in peripheral blood leukocytes with severity of ischemic stroke.

Human adrenomedullin (ADM), a 52-amino acid peptide, belongs to the calcitonin/calcitonin gene-related peptide (CGRP)/amylin peptide family. ADM acts as a multifunctional regulatory peptide and is upregulated in response to hypoxia. Previous microarray studies have found increased ADM gene (ADM) expression in peripheral blood cells of patients with stroke, however, it is unknown if an increased ADM level is correlated with severity of human ischemic stroke. This study investigated ADM expression in peripheral blood leukocytes (PBL) of healthy controls and subjects at day 1, week 1 and week 3 postacute ischemic stroke using rtPCR methodology. We found that ADM expression was significantly upregulated on the first day of stroke compared to the healthy subjects and the disease controls; the levels remained elevated for up to week 3. Further, ADM expression at day 1 was correlated with stroke severity measured by the National Institute of Healthy Stroke Scale (NIHSS), the modified Barthel Index (mBI) and the modified Rankin Scale (mRS). This could indicate that ADM expression level is related to the severity of tissue damage. We suggest that increased ADM expression in PBL after acute ischemic stroke is most likely to indicate that these cells have been subjected to hypoxia and that the magnitude of expression is likely to be related to the volume of hypoxic tissue. Hypoxia can affect lymphocytes function and could affect the immune response to stroke. The correlation of ADM expression level with the measures of stroke severity implicates ADM--a potential blood bio-marker in studies of ischemic stroke.

Management of failed flow diversion for intracranial aneurysm beyond the first 6 months of follow-up: an international Delphi consensus.

OBJECTIVE: The placement of flow-diverting devices has become a common method of treating unruptured intracranial aneurysms of the internal carotid artery. The progressive improvement of aneurysm occlusion after treatment-with low complication and rupture rates-has led to a dilemma regarding the management of aneurysms in which occlusion has not occurred within 6-24 months. The authors aimed to identify clinical consensus regarding management of intracranial aneurysms displaying persistent filling 6-24 months after flow diversion and to ascertain questions that may drive future investigation. METHODS: An international panel of 67 experts was invited to participate in a multistep Delphi consensus process on the treatment of intracranial aneurysms after failed flow diversion. RESULTS: Of the 67 experts invited, 23 (34%) participated. Qualitative analysis of an initial survey with open-ended questions resulted in 51 statements regarding management of aneurysms showing persistent filling after flow diversion. The statements were grouped into 8 categories, and in the second round, respondents rated the degree of their agreement with each statement on a 5-point Likert scale. Flow diverters with surface modifiers did not influence administration of dual-antiplatelet therapy according to 83%. Consensus was also reached regarding the definition of treatment failure at specific time points, including at 6 months if there is aneurysm growth or persistent rapid flow through the entirety of the aneurysm (96%), at 12 months if there is aneurysm growth or symptom onset (78%), and at 24 months if there is persistent filling regardless of size and filling characteristics (74%). Although experts agreed that the degree of intimal hyperplasia or in-device stenosis could not be ascertained by noninvasive imaging alone (83%), only 65% chose digital subtraction angiography as the preferred modality. At 6 and 12 months, retreatment is preferred if there is persistent filling with aneurysm growth (96%, 96%), device malposition (48%, 87%), or a history of subarachnoid hemorrhage (65%, 70%), respectively, and at 24 months if there is persistent filling without reduction in aneurysm size (74%). Experts favored treatment with an additional flow diverter (87%) over aneurysm clipping, applying the same principles for follow-up (83%) and treatment failure (91%) as for the first flow diverter. CONCLUSIONS: The authors present the consensus practices of experts in the management of intracranial aneurysms without occlusion 6-24 months after treatment with a flow-diverting device.

The physical anthropometry, lifestyle habits and blood pressure of people presenting with a first clinical demyelinating event compared to controls: the Ausimmune study.

INTRODUCTION: Lifestyle factors prior to a first clinical demyelinating event (FCD), a disorder often preceding the development of clinically definite multiple sclerosis (MS), have not previously been examined in detail. Past tobacco smoking has been consistently associated with MS. METHODS: This was a multicentre incident case-control study. Cases (n = 282) were aged 18-59 years with an FCD and resident within one of four Australian centres (from latitudes 27°S to 43°S), from 1 November 2003 to 31 December 2006. Controls (n = 558) were matched to cases on age, sex and study region, without CNS demyelination. Exposures measured included current and past tobacco and marijuana, alcohol and beverage use, physical activity patterns, blood pressure and physical anthropometry. RESULTS: A history of smoking ever was associated with FCD risk (AOR 1.89 (95%CL 1.82, 3.52)). Marijuana use was not associated with FCD risk after adjusting for confounders such as smoking ever but the estimates were imprecise because of a low prevalence of use. Alcohol consumption was common and not associated with FCD risk. No case-control differences in blood pressure or physical anthropometry were observed. CONCLUSIONS: Past tobacco smoking was positively associated with a risk of FCD but most other lifestyle factors were not. Prevention efforts against type 2 diabetes and cardiovascular disease by increasing physical activity and reducing obesity are unlikely to alter MS incidence, and more targeted campaigns will be required.

Where does the gadolinium go? A review into the excretion and retention of intravenous gadolinium.

Gadolinium-based contrast agents (GBCAs) are commonly used in medical imaging. Most intravenously (IV) administered gadolinium is excreted via the kidneys, and pathological retention in renal failure leading to nephrogenic systemic fibrosis (NSF) is well described. More recently, retention of gadolinium in the body in the absence of renal disease has been identified, with unknown clinical consequences. Many patients are aware of this, either through the media or via comprehensive consent documentation. Some internet sites, without hard evidence, have suggested a constellation of possible symptoms associated with GBCA retention. Recent experience with patients ascribing symptoms to a contrast-enhanced MRI examination prompted this review of the fate of injected GBCA after MRI study, and of information available to patients online regarding gadolinium retention.

Direct evidence of intra- and interhemispheric corticomotor network degeneration in amyotrophic lateral sclerosis: an automated MRI structural connectivity study.

Although the pathogenesis of amyotrophic lateral sclerosis (ALS) is uncertain, there is mounting neuroimaging evidence to suggest a mechanism involving the degeneration of multiple white matter (WM) motor and extramotor neural networks. This insight has been achieved, in part, by using MRI Diffusion Tensor Imaging (DTI) and the voxelwise analysis of anisotropy indices, along with DTI tractography to determine which specific motor pathways are involved with ALS pathology. Automated MRI structural connectivity analyses, which probe WM connections linking various functionally discrete cortical regions, have the potential to provide novel information about degenerative processes within multiple white matter (WM) pathways. Our hypothesis is that measures of altered intra- and interhemispheric structural connectivity of the primary motor and somatosensory cortex will provide an improved assessment of corticomotor involvement in ALS. To test this hypothesis, we acquired High Angular Resolution Diffusion Imaging (HARDI) scans along with high resolution structural images (sMRI) on 15 patients with clinical evidence of upper and lower motor neuron involvement, and 20 matched control participants. Whole brain probabilistic tractography was applied to define specific WM pathways connecting discrete corticomotor targets generated from anatomical parcellation of sMRI of the brain. The integrity of these connections was interrogated by comparing the mean fractional anisotropy (FA) derived for each WM pathway. To assist in the interpretation of results, we measured the reproducibility of the FA summary measures over time (6months) in control participants. We also incorporated into our analysis pipeline the evaluation and replacement of outlier voxels due to head motion and physiological noise. When assessing corticomotor connectivity, we found a significant reduction in mean FA within a number of intra- and interhemispheric motor pathways in ALS patients. The abnormal intrahemispheric pathways include the corticospinal tracts involving the left and right precentral gyri (lh.preCG, rh.preCG) and brainstem (bs); right postcentral gyrus (rh.postCG) and bs; lh.preCG and left posterior cingulate gyrus (lh.PCG); rh.preCG and right posterior cingulate gyrus (rh.PCG); and the rh.preCG and right paracentral gyrus (rh.paraCG). The abnormal interhemispheric pathways included the lh.preCG and rh.preCG; lh.preCG and rh.paraCG; lh.preCG and right superior frontal gyrus (rh.supFG); lh.preCG and rh.postCG; rh.preCG and left paracentral gyrus (lh.paraCG); rh.preCG and left superior frontal gyrus (lh.supFG); and the rh.preCG and left caudal middle frontal gyrus (lh.caudMF). The reproducibility of the measurement of these pathways was high (variation less than 5%). Maps of the outlier rejection voxels, revealed clusters within the corpus callosum and corticospinal projections. This finding highlights the importance of correcting for motion artefacts and physiological noise when studying clinical populations. Our novel findings, many of which are consistent with known pathology, show extensive involvement and degeneration of multiple corticomotor pathways in patients with upper and lower motor neuron signs and provide support for the use of automated structural connectivity techniques for studying neurodegenerative disease processes.

Neuroferritinopathy: a new inborn error of iron metabolism.

Neuroferritinopathy is an autosomal dominant progressive movement disorder which occurs due to mutations in the ferritin light chain gene (FTL1). It presents in mid-adult life and is the only autosomal dominant disease in a group of conditions termed neurodegeneration with brain iron accumulation (NBIA). We performed brain MRI scans on 12 asymptomatic descendants of known mutation carriers. All three harbouring the pathogenic c.460InsA mutation showed iron deposition; these findings show pathological iron accumulation begins in early childhood which is of major importance in understanding and developing treatment for NBIA.

Intracranial perianeurysmal cysts: case series and review of the literature.

BACKGROUND: Intracranial perianeurysmal cysts are a rare finding associated with cerebral aneurysms. Patients may present with symptoms secondary to mass effect from perianeurysmal cysts requiring drainage. These lesions can masquerade as neoplasms if dedicated vascular imaging is not performed, leading to misdiagnosis. METHOD: A retrospective search of our database was done for intracranial aneurysms that have been treated between 1998 and 2020. A literature search was then performed on PubMed and Google Scholar with the search terms 'aneurysm', 'intracranial/intracerebral', 'cyst', and 'perianeurysmal cyst'. Patient demographics, aneurysms and cysts characteristics were then summarized as a table and in the discussion. RESULTS: Three cases where intracranial aneurysm had associated perianeurysmal cysts were found in our database. Combined with the available literature a total of 19 cases of perianeurysmal cysts have thus far been reported since this entity was first described in 2002. A significant number of perianeurysmal cysts (5/19) required intervention. In 5/19 cases the patient presented with a perianeurysmal cyst without a history of subarachnoid hemorrhage. Of the 10 cases where aneurysm follow-up was reported there were 5 cases where there was aneurysm recurrence necessitating re-treatment. CONCLUSION: Significant variability exists in the patient demographics, aneurysm and cyst characteristics of perianeurysmal cysts. This suggests that there is no single unified etiology and pathogenesis. These lesions are a rare finding and at present do not appear to carry diagnostic or prognostic significance. Management of perianeurysmal cysts is case-dependent and intervention should be considered when treating the related aneurysm, especially in patients with secondary symptoms.

The role of latitude, ultraviolet radiation exposure and vitamin D in childhood asthma and hayfever: an Australian multicenter study.

Observations of increasing allergy prevalence with decreasing distance from the Equator and positive associations with ambient ultraviolet radiation have contributed to a growing interest in the possible role of vitamin D in the etiology of allergy. The aims of this study were to describe any latitudinal variation in the prevalence of childhood allergy in Australia and to evaluate, in parallel, the individual associations between ultraviolet radiation (UVR)- and vitamin D-related measures and hayfever asthma and both conditions. Participants were population-based controls who took part in a multicenter case-control study, aged 18-61 yr and resident in one of four study regions ranging in latitude from 27°S to 43°S. Data were derived from a self-administered questionnaire, interview and examination by a research officer and biologic sampling. Latitude and longitude coordinates were geocoded from participants' residential locations and climatic data were linked to postcodes of current residence. Stored serum was analyzed for 25-hydroxyvitamin D concentrations and silicone rubber casts of the skin were used as an objective measure of cumulative actinic damage. There was an inverse latitude gradient for asthma (a 9% decrease per increasing degree of latitude); however, this pattern did not persist after adjusting for average daily temperature. There was no association between any of the UVR- or vitamin D-related measures and childhood asthma, but greater time in the sun in winter between the ages 6-15 yr was associated with an increase in the odds of having hayfever [adjusted odds ratios (OR) 1.29; 95% CI 1.01-1.63]. Oral supplementation with cod liver oil in childhood increased the odds of a history of having both asthma and hayfever (2.87; 1.00-8.32). Further investigation of the possible role of early vitamin D supplementation in the development of allergy is warranted. Our results also suggest that solar exposure during childhood may be important in allergic sensitization. Plausible explanations, including biologic mechanisms, exist for both observations.

Treatment of a middle cerebral artery aneurysm in the setting of Loeys-Dietz syndrome: Case report and review of literature.

Loeys-Dietz syndrome (LDS) is a connective tissue disorder with associated systemic vasculopathies including intracranial arterial aneurysm formation and dissections. LDS is a relatively less well-known entity compared with other connective tissue disorders, such as Ehlers-Danlos or Marfan syndrome, and consequently experience in the management of the associated intracranial aneurysms is suboptimal. We present a case of surgical clipping of a middle cerebral artery aneurysm in a patient with LDS. A 46-year-old female with LDS (type III) was found to have a right middle cerebral artery (MCA) bifurcation aneurysm following vascular screening. The decision was made to surgically clip the aneurysm after consultation in our neurovascular multidisciplinary team meeting. A standard right pterional craniotomy was performed and the aneurysm was secured with 2 straight Sugita clips. The temporal M2 branch was noted to be thin walled and this prompted application of the second tandem clip, rather than risk re-positioning the initial clip. In our case, the MCA aneurysm neck was robust enough to take a clip without any complications, and therefore we suggest that the presence of LDS is not an absolute contra-indication to perform open craniotomy and clipping.

Sustained Clinical Improvement in a Subset of Patients With Progressive Multiple Sclerosis Treated With Epstein-Barr Virus-Specific T Cell Therapy.

Background: Increasing evidence indicates a role for Epstein-Barr virus (EBV) in the pathogenesis of multiple sclerosis (MS). EBV-infected autoreactive B cells might accumulate in the central nervous system because of defective cytotoxic CD8+ T cell immunity. We have previously reported results of a phase I clinical trial of autologous EBV-specific T cell therapy in MS 6 months after treatment. Objective: To investigate longer-term outcomes in MS patients who received autologous EBV-specific T cell therapy. Methods: We assessed participants 2 and 3 years after completion of T cell therapy. Results: We collected data from all 10 treated participants at year 2 and from 9 participants at year 3. No serious treatment-related adverse events were observed. Four participants had at least some sustained clinical improvement at year 2, including reduced fatigue in three participants, and reduced Expanded Disability Status Scale score in two participants. Three participants experienced a sustained improvement in at least some symptoms at year 3. More sustained improvement was associated with higher EBV-specific CD8+ T cell reactivity in the administered T cell product. Conclusion: Autologous EBV-specific T cell therapy is well-tolerated, and some degree of clinical improvement can be sustained for up to 3 years after treatment.

Peripherally Inserted Central catheter iNnovation to reduce Infections and Clots (the PICNIC trial): a randomised controlled trial protocol.

INTRODUCTION: Peripherally inserted central catheters (PICCs) are vital for the delivery of medical therapies, but up to 30% of PICCs are associated with complications such as deep vein thrombosis or infection. The integration of antimicrobial and hydrophobic catheter materials, and pressure-activated valves, into polyurethane PICCs are innovations designed to prevent infective and/or thrombotic complications. METHODS AND ANALYSIS: A multicentre, parallel group, superiority randomised controlled trial with two experimental arms ((1) hydrophobic PICC (with pressure-activated valve); (2) chlorhexidine gluconate-impregnated PICC (with external clamp)) and one control group ((3) conventional polyurethane PICC (with external clamp)). Recruitment of 1098 adult and paediatric patients will take place over 2 years at three tertiary-referral hospitals in Queensland, Australia. Patients are eligible for inclusion if their PICC is to be inserted for medical treatment, with a vascular size sufficient to support a 4-Fr PICC or larger, and with informed consent. The primary outcome is PICC failure, a composite of thrombotic (venous thrombosis, breakage and occlusion) and infective complications (PICC-associated bloodstream infection and local infection). Secondary outcomes include: all-cause PICC complication; thrombotic complications; infective complications; adverse events (local or systemic reaction); PICC dwell time; patient/parent satisfaction; and healthcare costs. Differences between both intervention groups and the control group will be compared using Cox proportional hazards regression. Effect estimates will be presented as HRs with corresponding 95% CI. ETHICS AND DISSEMINATION: Ethical approval from Queensland Health (HREC/QCHQ/48682) and Griffith University (Ref. No. 2019/094). Results will be published. TRIAL REGISTRATION NUMBER: ACTRN12619000022167.