Preoperative embolisation of brain arteriovenous malformations: a systematic review and meta-analysis

Preoperative embolisation is a commonly performed adjunct to microsurgical excision of brain arteriovenous malformations (bAVMs), with aims such as lessening the technical difficulty of the microsurgical procedure, reducing operative time, decreasing blood loss, and improving patient functional outcomes. We aim to perform a systematic review of randomised trials and cohort studies evaluating preoperative embolisation of bAVMs published between 01 January 2000 and 31 March 2021 and appraise its role in clinical practice. A MEDLINE search was performed, and articles reporting on outcomes following preoperative embolisation, as an adjunct to microsurgery, were eligible for inclusion. PRISMA reporting and Cochrane Handbook guidelines were followed. The primary outcome measure was the risk of complications associated with preoperative embolisation. The study was registered with PROSPERO (CRD42021244231). Of the 1661 citations, 8 studies with 588 patients met predefined inclusion criteria. No studies specifically compared outcomes of surgical excision of bAVMs between those with and without preoperative embolisation. Spetzler Martin (SM) grading was available in 301 cases. 123 of 298 (41?28%) patients presented with haemorrhage. Complications related to embolisation occurred in 175/588 patients (29.4%, 95% CI 19.6–40.2). Permanent neurological deficits occurred in 36/541 (6%, 95% CI 3.9–8.5) and mortality in 6/588 (0.41%, 95% CI 0–1.4). This is the first systematic review evaluating preoperative embolisation of bAVMs. Existing studies assessing this intervention are of poor quality. Associated complication rates are significant. Based on published literature, there is currently insufficient evidence to recommend preoperative embolisation of AVMs. Further studies are required to ascertain if there are benefits of this procedure and if so, in which cases.

     

The astrocyte in multiple sclerosis revisited

Among the constituent cell types of the multiple sclerosis (MS) plaque, the astrocyte has been the least considered as a player in the pathogenesis of the lesion. Traditionally, it has been assigned a secondary scarring role with little or no role in lesion formation or repair. However, the recent upsurge of interest in the demyelinating condition neuromyelitis optica (NMO) has resulted in NMO being identified as the first disease of myelin in which primary damage to astrocytes, resulting from a humoral immune response that forms against the water channel aquaporin‐4, has been documented. This finding in NMO prompted us to re‐examine data and material from cases of MS displaying active lesions. Our reappraisal revealed unambiguous early damage to perivascular astrocyte end‐feet and to hypertrophic astrocytes in the adjacent parenchyma, but whether this was a primary event was difficult to evaluate due to concomitant edema and inflammation in these acute lesions. The astrocyte damage was long‐lasting since resolving lesions displaying remyelination also showed defects in the integrity of the astrocytic covering around blood vessels. Analysis of our findings and of the astrocytic literature supports multiple roles for the astrocyte in the evolution of changes encountered in MS depending upon lesion stage and lesion topography. At variance with the somewhat inhibitory role of the astrocyte is the abundant and growing evidence for this cell to actively participate in both lesion development and repair. We propose that the unequivocal selective early involvement of the astrocyte in MS lesions may have therapeutic relevance. © 2013 Wiley Periodicals, Inc.     

Adolescents with Autism Spectrum Disorder Show a Circumspect Reasoning Bias Rather than ‘Jumping-to-Conclusions’

People with autism spectrum disorders (ASD) often take longer to make decisions. The Autism-Psychosis Model proposes that people with autism and psychosis show the opposite pattern of results on cognitive tasks. As those with psychosis show a jump-to-conclusions reasoning bias, those with ASD should show a circumspect reasoning bias. Jumping-to-conclusions was assessed in a sample of 20 adolescents with ASD and 23 age-matched controls using the jumping-to-conclusions beads task. Both groups demonstrated equivalent levels of confidence in decision-making, however the ASD group required more beads than controls before making their decision. Furthermore, there was a positive correlation between the beads required and degree of autism symptoms. Consistent with the Autism-Psychosis Model, a more circumspect reasoning bias was evident in ASD.     

Biomarkers for Type 2 Diabetes and Impaired Fasting Glucose Using a Nontargeted Metabolomics Approach

Using a nontargeted metabolomics approach of 447 fasting plasma metabolites, we searched for novel molecular markers that arise before and after hyperglycemia in a large population-based cohort of 2,204 females (115 type 2 diabetic [T2D] case subjects, 192 individuals with impaired fasting glucose [IFG], and 1,897 control subjects) from TwinsUK. Forty-two metabolites from three major fuel sources (carbohydrates, lipids, and proteins) were found to significantly correlate with T2D after adjusting for multiple testing; of these, 22 were previously reported as associated with T2D or insulin resistance. Fourteen metabolites were found to be associated with IFG. Among the metabolites identified, the branched-chain keto-acid metabolite 3-methyl-2-oxovalerate was the strongest predictive biomarker for IFG after glucose (odds ratio [OR] 1.65 [95% CI 1.39–1.95], P = 8.46 × 10⁻⁹) and was moderately heritable (h² = 0.20). The association was replicated in an independent population (n = 720, OR 1.68 [ 1.34–2.11], P = 6.52 × 10⁻⁶) and validated in 189 twins with urine metabolomics taken at the same time as plasma (OR 1.87 [1.27–2.75], P = 1 × 10⁻³). Results confirm an important role for catabolism of branched-chain amino acids in T2D and IFG. In conclusion, this T2D-IFG biomarker study has surveyed the broadest panel of nontargeted metabolites to date, revealing both novel and known associated metabolites and providing potential novel targets for clinical prediction and a deeper understanding of causal mechanisms.Currently, stratification of individuals at risk for type 2 diabetes (T2D) within the general population is based on well-established factors such as age, BMI, and fasting glucose (1). Although these factors contribute considerably to disease risk, they may not identify at-risk individuals before the disease process is well under way.Recently, a number of studies have found several metabolites to be correlated with insulin resistance and T2D (2–6), and T2D-associated metabolic profiles have been identified 10–15 years before the diagnosis/onset of the disease (7–9). To help preventive strategies, and maximize the potential for existing effective interventions, it is important to characterize the molecular changes that take place in the development of T2D.We aim to understand other biochemical changes, in addition to hyperglycemia, that take place at the onset of T2D using the largest metabolomic screening approach to date. We assessed >400 metabolites to determine which metabolomic profiles are correlated with T2D and impaired fasting glucose (IFG) in a large cohort of females from TwinsUK with independent replication.     

Inhibition of medium and short-chain fatty acid oxidation in rat heart mitochondria by dichloroacetate

The effect of dichloroacetate (DCA) on the oxidation of medium-chain and short-chain fatty acids was studied in rat heart mitochondria. Dichloroacetate (1–10 mM) markedly decreased medium-chain and short-chain fatty acid oxidation (oxygen uptake and release of ¹⁴CO₂ from labelled fatty acids) by heart mitochondria; the oxidation of long-chain fatty acid, however, was unaffected by the compound. The oxidation of acylcarnitines was not influenced by DCA. Dichloroacetate inhibited medium-chain and short-chain fatty acid oxidation by inhibiting the activity of mitochondrial acyl-CoA synthases. Inhibition of the enzyme activity by DCA was rapid and not due to its effect on pyruvate dehydrogenase.     

Responses to the Assurance game in monkeys, apes, and humans using equivalent procedures

There is great interest in the evolution of economic behavior. In typical studies, species are asked to play one of a series of economic games, derived from game theory, and their responses are compared. The advantage of this approach is the relative level of consistency and control that emerges from the games themselves; however, in the typical experiment, procedures and conditions differ widely, particularly between humans and other species. Thus, in the current study, we investigated how three primate species, capuchin monkeys, chimpanzees, and humans, played the Assurance (or Stag Hunt) game using procedures that were, to the best of our ability, the same across species, particularly with respect to training and pretesting. Our goal was to determine what, if any, differences existed in the ways in which these species made decisions in this game. We hypothesized differences along phylogenetic lines, which we found. However, the species were more similar than might be expected. In particular, humans who played using "nonhuman primate-friendly" rules did not behave as is typical. Thus, we find evidence for similarity in decision-making processes across the order Primates. These results indicate that such comparative studies are possible and, moreover, that in any comparison rating species' relative abilities, extreme care must be taken in ensuring that one species does not have an advantage over the others due to methodological procedures.     

Adverse dermatologic effects of cardiovascular drug therapy: part III

Cardiovascular disease is common, affecting an increasing number of persons as the population ages. To combat this growing health problem, physicians use a multitude of medications in the treatment of their patients. Although pharmacologic therapy greatly enhances quality of life for a majority of patients, there is always the potential for an unfavorable reaction. For example, cardiovascular drugs can induce a vast array of adverse dermatologic responses. This article reviews the various cutaneous reaction patterns that can occur as a result of treatment with vasodilators and other antihypertensive drugs, anticoagulants and antiplatelet drugs, thrombolytic agents, and lipid-lowering agents.