CNS inflammation other than multiple sclerosis: how likely is diagnosis?

The incidence, diagnostic landscape, and workload impact of CNS inflammatory diseases other than multiple sclerosis (MS) (CIDOMS) in a tertiary setting is unknown. We describe a retrospective case series of 64 patients identified over a 2-year period (2009–2010) at the Wessex Neurological Centre in the United Kingdom, accounting for 4% of all patients seen at the center. As expected, neurosarcoidosis and neuromyelitis optica (NMO) were the most common diagnoses reached (14% each); other diagnoses singly accounted for <10%. However, the likeliest diagnostic outcome (strikingly, in 25%) was nondiagnosis, despite intensive investigation and a mean follow-up period of 3 years. Undiagnosed patients with CIDOMS represented the largest workload of the neurology center

Lymphopenia in treatment-naive relapsing multiple sclerosis

Lymphopenia accompanies some autoimmune diseases. A number of studies, but not others, have suggested that lymphopenia occurs in treatment-naive multiple sclerosis (MS), so the issue remains unresolved. This is important since lymphopenia may identify an immunologically distinct subset of MS. Also, lymphopenia may emerge as a risk factor for serious viral infections of the brain during dimethyl fumarate treatment. We therefore embarked on a retrospective controlled study of pre-treatment lymphopenia in relapsing M

How do people with multiple sclerosis experience prognostic uncertainty and prognosis communication? A qualitative study

Background: Disease progression in multiple sclerosis (MS) is highly variable and predicting prognosis is notoriously challenging. Patients’ prognosis beliefs, responses to prognostic uncertainty and experiences of prognosis-related communication with healthcare professionals (HCPs) have received little study. These issues have implications for patients’ psychological adjustment and are important in the context of the recent development of personalised prognosis forecasting tools. This study explored patient perspectives on the experience of prognostic uncertainty, the formation of expectations about personal prognosis and the nature of received and desired prognosis communication. Methods: 15 MS patients participated in in-depth semi-structured interviews which were analysed using inductive thematic analysis. Results: Six themes captured key aspects of the data: Experiencing unsatisfactory communication with HCPs, Appreciating and accepting prognostic uncertainty, Trying to stay present-focused, Forming and editing personal prognosis beliefs, Ambivalence towards forecasting the future, and Prognosis information delivery. MS patients report having minimal communication with HCPs about prognosis. Over time MS patients appear to develop expectations about their disease trajectories, but do so with minimal HCP input. Provision of prognosis information by HCPs seems to run counter to patients’ attempts to remain present-focused. Patients are often ambivalent about prognosis forecasting and consider it emotionally dangerous and of circumscribed usefulness.Conclusions: HCPs must carefully consider whether, when and how to share prognosis information with patients; specific training may be beneficial. Future research should confirm findings about limited HCP-patient communication, distinguish predictors of patients’ attitudes towards prognostication and identify circumstances under which prognostic forecasting benefits patients. <br/

Electrical resistivity of pure copper processed by medium-powered laser powder bed fusion additive manufacturing for use in electromagnetic applications

Pure copper is an excellent thermal and electrical conductor, however, attempts to process it with additive manufacturing (AM) technologies have seen various levels of success. While electron beam melting (EBM) has successfully processed pure copper to high densities, laser powder bed fusion (LPBF) has had difficulties achieving the same results without the use of very high power lasers. This requirement has hampered the exploration of using LPBF with pure copper as most machines are equipped with lasers that have low to medium laser power densities. In this work, experiments were conducted to process pure copper with a 200 W LPBF machine with a small laser spot diameter resulting in an above average laser power density in order to maximise density and achieve low electrical resistivity. The effects of initial build orientation and post heat treatment were also investigated to explore their influence on electrical resistivity. It was found that despite issues with high porosity, heat treated specimens had a lower electrical resistivity than other common AM materials such as the aluminium alloy AlSi10Mg. By conducting these tests, it was found that despite having approximately double the resistivity of commercially pure copper, the resistivity was sufficiently low enough to demonstrate the potential to use AM to process copper suitable for electrical applications

The heme-hemopexin scavenging system is active in the brain, and associates with outcome after subarachnoid hemorrhage

Background and Purpose – Long-term outcome after subarachnoid hemorrhage (SAH) is potentially linked to cytotoxic heme. Free heme is bound by hemopexin (Hpx) and rapidly scavenged by CD91. We hypothesized that heme scavenging in the brain would be associated with outcome after haemorrhage. Methods - Using cerebrospinal fluid (CSF) and tissue from SAH patients and control individuals, the activity of the intracranial CD91-Hpx system was examined using enzyme-linked immunoassays, ultra-high performance liquid chromatography and immunohistochemistry. Results - In control individuals, CSF Hpx was mainly synthesized intrathecally. After SAH, CSF Hpx was high in one-third of cases, and these patients had a higher probability of delayed cerebral ischaemia and poorer neurological outcome. The intracranial CD91-Hpx system was active after SAH since CD91 positively correlated with iron deposition in brain tissue. Heme-Hpx uptake saturated rapidly after SAH, since bound heme accumulated early in the CSF. When the blood-brain barrier was compromised following SAH, serum Hpx level was lower, suggesting heme transfer to the circulation for peripheral CD91 scavenging. Conclusions - The CD91-heme-Hpx scavenging system is important after SAH and merits further study as a potential prognostic marker and therapeutic target

National analyses on survival in Maltese adult patients on renal replacement therapy started during 2009–2012

Chronic kidney disease patients on maintenance dialysis (CKD 5D) experience major morbidity and mortality. No data on survival in Maltese dialysis patients exist; therefore, the aim of this study was to rigorously examine survival statistics in a complete cohort of Maltese CKD 5D patients. The study population was comprised of all incident chronic patients (N=328) starting dialysis at the renal unit, Mater Dei hospital, Msida, Malta, for 4 consecutive years (2009–2012). Each yearly cohort was analysed in detail up to 31st December 2017, providing up to 8 years follow-up. Demographics (male 65%; female 35%), aetiology of renal failure (diabetic kidney disease: n=191; 58.2%), comorbidities, transplant status, and death were documented. Data collection and follow up were completed and statistical analysis was performed on the aggregated cohorts with SPSS version 23 with censoring up to 31st December 2017. The cumulative adjusted 5-year overall survival in Maltese CKD 5D patients was 0.36 and 0.25 at 8 years. No statistical difference was observed according to the year of starting dialysis. Cox regression analysis showed that age and transplant status influenced survival. The unadjusted hazard of death increased by 3% for every 1-year increase in age and was increased by 7% if the patient did not receive a transplant, and overall 22% (n=72) of the entire cohort eventually received transplants. This study reports an approximate 65% mortality at 5 years in Maltese haemodialysis patients, a poor prognosis that, despite optimal medical management, is consistent with worldwide reports.peer-reviewe

Haptoglobin Treatment for Aneurysmal Subarachnoid Hemorrhage: Review and Expert Consensus on Clinical Translation

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating form of stroke frequently affecting young to middle-aged adults, with an unmet need to improve outcome. This special report focusses on the development of intrathecal haptoglobin supplementation as a treatment by reviewing current knowledge and progress, arriving at a Delphi-based global consensus regarding the pathophysiological role of extracellular hemoglobin and research priorities for clinical translation of hemoglobin-scavenging therapeutics. After aneurysmal subarachnoid hemorrhage, erythrocyte lysis generates cell-free hemoglobin in the cerebrospinal fluid, which is a strong determinant of secondary brain injury and long-term clinical outcome. Haptoglobin is the body’s first-line defense against cell-free hemoglobin by binding it irreversibly, preventing translocation of hemoglobin into the brain parenchyma and nitric oxide-sensitive functional compartments of cerebral arteries. In mouse and sheep models, intraventricular administration of haptoglobin reversed hemoglobin-induced clinical, histological, and biochemical features of human aneurysmal subarachnoid hemorrhage. Clinical translation of this strategy imposes unique challenges set by the novel mode of action and the anticipated need for intrathecal drug administration, necessitating early input from stakeholders. Practising clinicians (n=72) and scientific experts (n=28) from 5 continents participated in the Delphi study. Inflammation, microvascular spasm, initial intracranial pressure increase, and disruption of nitric oxide signaling were deemed the most important pathophysiological pathways determining outcome. Cell-free hemoglobin was thought to play an important role mostly in pathways related to iron toxicity, oxidative stress, nitric oxide, and inflammation. While useful, there was consensus that further preclinical work was not a priority, with most believing the field was ready for an early phase trial. The highest research priorities were related to confirming haptoglobin’s anticipated safety, individualized versus standard dosing, timing of treatment, pharmacokinetics, pharmacodynamics, and outcome measure selection. These results highlight the need for early phase trials of intracranial haptoglobin for aneurysmal subarachnoid hemorrhage, and the value of early input from clinical disciplines on a global scale during the early stages of clinical translation

Electrical resistivity of additively manufactured AlSi10Mg for use in electric motors

Additive manufacturing (AM) opens up a design freedom beyond the limits of traditional manufacturing techniques. Electrical windings created through AM could lead to more powerful and compact electric motors, but only if the electrical properties of the AM printed part can be shown to be similar to conventionally manufactured systems. Until now, no study has reported on the suitability of AM parts for electrical applications as there are few appropriate materials available to AM for this purpose. AlSi10Mg is a relatively good electrical conductor that does not have the same reported issues associated with processing pure aluminium or copper via selective laser melting (SLM). Here, experiments were conducted to test the effects of geometry and heat treatments on the resistivity of AlSi10Mg processed by SLM. It was found that post heat treatments resulted in a resistivity that was 33% lower than the as-built material. The heat treatment also eliminated variance in the resistivity of as-built parts due to initial build orientation. By conducting these tests, it was found that, with this material, there is no penalty in terms of higher resistivity for using AM in electrical applications, thus allowing more design freedom in future electrical applications