Do animal models of brain tumors replicate human peritumoral edema? a systematic literature search.

INTRODUCTION: Brain tumors cause morbidity and mortality in part through peritumoral brain edema. The current main treatment for peritumoral brain edema are corticosteroids. Due to the increased recognition of their side-effect profile, there is growing interest in finding alternatives to steroids but there is little formal study of animal models of peritumoral brain edema. This study aims to summarize the available literature. METHODS: A systematic search was undertaken of 5 literature databases (Medline, Embase, CINAHL, PubMed and the Cochrane Library). The generic strategy was to search for various terms associated with "brain tumors", "brain edema" and "animal models". RESULTS: We identified 603 reports, of which 112 were identified as relevant for full text analysis that studied 114 peritumoral brain edema animal models. We found significant heterogeneity in the species and strain of tumor-bearing animals, tumor implantation method and edema assessment. Most models did not produce appreciable brain edema and did not test for observable manifestations thereof. CONCLUSION: No animal model currently exists that enable the investigation of novel candidates for the treatment of peritumoral brain edema. With current interest in alternative treatments for peritumoral brain edema, there is an unmet need for clinically relevant animal models.

Systematic review of radiological cervical foraminal grading systems.

The study design of this paper is systematic review. The purpose of this review is to evaluate the existing radiological grading systems that are used to assess cervical foraminal stenosis. The importance of imaging the cervical spine using CT or MRI in evaluating cervical foraminal stenosis is widely accepted; however, there is no consensus for standardized methodology to assess the compression of the cervical nerve roots. A systematic search of Ovid Medline databases, Embase 1947 to present, Cinahl, Web of Science, Cochrane Library, ISRCTN and WHO international clinical trials was performed for reports of cervical foraminal stenosis published before 01 February 2020. In collaboration with the University of Leeds, a search strategy was developed. A total of 6952 articles were identified with 59 included. Most of the reports involved multiple imaging modalities with standard axial and sagittal imaging used most. The grading themes that came from this systematic review show that the most mature for cervical foraminal stenosis is described by (Kim et al. Korean J Radiol 16:1294, 2015) and (Park et al. Br J Radiol 86:20120515, 2013). Imaging of the cervical nerve root canals is mostly performed using MRI and is reported using subjective terminology. The Park, Kim and Modified Kim systems for classifying the degree of stenosis of the nerve root canal have been described. Clinical application of these scoring systems is limited by their reliance on nonstandard imaging (Park), limited validation against clinical symptoms and surgical outcome data. Oblique fine cut images derived from three dimensional MRI datasets may yield more consistency, better clinical correlation, enhanced surgical decision-making and outcomes.

Surgically generated aerosol and mitigation strategies: combined use of irrigation, respirators and suction massively reduces particulate matter aerosol.

BACKGROUND: Aerosol is a health risk to theatre staff. This laboratory study quantifies the reduction in particulate matter aerosol concentrations produced by electrocautery and drilling when using mitigation strategies such as irrigation, respirator filtration and suction in a lab environment to prepare for future work under live OR conditions. METHODS: We combined one aerosol-generating procedure (monopolar cutting or coagulating diathermy or high-speed diamond- or steel-tipped drilling of cadaveric porcine tissue) with one or multiple mitigation strategies (instrument irrigation, plume suction and filtration using an FFP3 respirator filter) and using an optical particle counter to measure particulate matter aerosol size and concentrations. RESULTS: Significant aerosol concentrations were observed during all aerosol-generating procedures with concentrations exceeding 3 × 106 particles per 100 ml. Considerable reductions in concentrations were observed with mitigation. In drilling, suction, FFP3 filtration and wash alone respectively reduced aerosol by 19.3-31.6%, 65.1-70.8% and 97.2 to > 99.9%. The greatest reduction (97.38 to > 99.9%) was observed when combining irrigation and filtration. Coagulating diathermy reduced concentrations by 88.0-96.6% relative to cutting, but produced larger particles. Suction alone, and suction with filtration reduced aerosol concentration by 41.0-49.6% and 88.9-97.4% respectively. No tested mitigation strategies returned aerosol concentrations to baseline. CONCLUSION: Aerosol concentrations are significantly reduced through the combined use of filtration, suction and irrigation. Further research is required to characterise aerosol concentrations in the live OR and to find acceptable exposure limits, and in their absence, to find methods to further reduce exposure to theatre staff.

Fronto-orbital advancement and reconstruction using reverse frontal bone graft without the use of orbital bar: a technical note.

INTRODUCTION: We describe our technique of using reverse frontal bone graft for FOAR for patients with metopic or coronal synostosis and present our complications using the Leeds classification system for complications in craniosynostosis surgery. METHODS: Since April 2015, seventeen patients have been operated using this technique. We perform a frontal bone graft that is then reversed, and supraorbital margins are drilled out. The orbital bar is then removed and drilled down to make bone dust and on-lay bone grafts which are then used to fill gaps on exposed dura and fill in around the temporal region. RESULTS: All 17 patients who underwent this technique have good cosmetic results. We report 5 (29%) complications and 8 (47%) blood transfusions (7 exposures, 1 cell salvage).

Evaluation of nationwide referral pathways, investigation and treatment of suspected cauda equina syndrome in the United Kingdom.

Purpose: Cauda equina syndrome (CES) is a spinal emergency with clinical symptoms and signs that have low diagnostic accuracy. National guidelines in the United Kingdom (UK) state that all patients should undergo an MRI prior to referral to specialist spinal units and surgery should be performed at the earliest opportunity. We aimed to evaluate the current practice of investigating and treating suspected CES in the UK. Materials and Methods: A retrospective, multicentre observational study of the investigation and management of patients with suspected CES was conducted across the UK, including all patients referred to a spinal unit over 6 months between 1st October 2016 and 31st March 2017. Results: A total of 28 UK spinal units submitted data on 4441 referrals. Over half of referrals were made without any previous imaging (n = 2572, 57.9%). Of all referrals, 695 underwent surgical decompression (15.6%). The majority of referrals were made out-of-hours (n = 2229/3517, 63.4%). Patient location and pre-referral imaging were not associated with time intervals from symptom onset or presentation to decompression. Patients investigated outside of the spinal unit experienced longer time intervals from referral to undergoing the MRI scan. Conclusions: This is the largest known study of the investigation and management of suspected CES. We found that the majority of referrals were made without adequate investigations. Most patients were referred out-of-hours and many were transferred for an MRI without subsequently requiring surgery. Adherence to guidelines would reduce the number of referrals to spinal services by 72% and reduce the number of patient transfers by 79%.

Bidirectional Modulation of Alcohol-Associated Memory Reconsolidation through Manipulation of Adrenergic Signaling.

Alcohol addiction is a problem of great societal concern, for which there is scope to improve current treatments. One potential new treatment for alcohol addiction is based on disrupting the reconsolidation of the maladaptive Pavlovian memories that can precipitate relapse to drug-seeking behavior. In alcohol self-administering rats, we investigated the effects of bidirectionally modulating adrenergic signaling on the strength of a Pavlovian cue-alcohol memory, using a behavioral procedure that isolates the specific contribution of one maladaptive Pavlovian memory to relapse, the acquisition of a new alcohol-seeking response for an alcohol-associated conditioned reinforcer. The ß-adrenergic receptor antagonist propranolol, administered in conjunction with memory reactivation, persistently disrupted the memory that underlies the capacity of a previously alcohol-associated cue to act as a conditioned reinforcer. By contrast, enhancement of adrenergic signaling by administration of the adrenergic prodrug dipivefrin at reactivation increased the strength of the cue-alcohol memory and potentiated alcohol seeking. These data demonstrate the importance of adrenergic signaling in alcohol-associated memory reconsolidation, and suggest a pharmacological target for treatments aiming to prevent relapse through the disruption of maladaptive memories.

Task rules, working memory, and fluid intelligence.

Many varieties of working memory have been linked to fluid intelligence. In Duncan et al. (Journal of Experimental Psychology:General 137:131-148, 2008), we described limited working memory for new task rules: When rules are complex, some may fail in their control of behavior, though they are often still available for explicit recall. Unlike other kinds of working memory, load is determined in this case not by real-time performance demands, but by the total complexity of the task instructions. Here, we show that the correlation with fluid intelligence is stronger for this aspect of working memory than for several other, more traditional varieties-including simple and complex spans and a test of visual short-term memory. Any task, we propose, requires construction of a mental control program that aids in segregating and assembling multiple task parts and their controlling rules. Fluid intelligence is linked closely to the efficiency of constructing such programs, especially when behavior is complex and novel.

Antagonism at NMDA receptors, but not ß-adrenergic receptors, disrupts the reconsolidation of pavlovian conditioned approach and instrumental transfer for ethanol-associated conditioned stimuli.

RATIONALE: Reconsolidation is the process by which memories require restabilisation following destabilisation at retrieval. Since even old, well-established memories become susceptible to disruption following reactivation, treatments based upon disrupting reconsolidation could provide a novel form of therapy for neuropsychiatric disorders based upon maladaptive memories, such as drug addiction. Pavlovian cues are potent precipitators of relapse to drug-seeking behaviour and influence instrumental drug seeking through at least three psychologically and neurobiologically distinct processes: conditioned reinforcement, conditioned approach (autoshaping) and conditioned motivation (pavlovian-instrumental transfer or PIT). We have previously demonstrated that the reconsolidation of memories underlying the conditioned reinforcing properties of drug cues depends upon NMDA receptor (NMDAR)- and ß-adrenergic receptor (ßAR)-mediated signalling. However, it is unknown whether the drug cue memory representations underlying conditioned approach and PIT depend upon the same mechanisms. OBJECTIVES: Using orally self-administered ethanol as a reinforcer in two separate experiments, we investigated whether the reconsolidation of the memories underlying conditioned approach and PIT requires ßAR- and NMDAR-dependent neurotransmission. RESULTS: For ethanol self-administering but non-dependent rats, the memories underlying conditioned approach and PIT for a pavlovian drug cue were disrupted by the administration of the NMDAR antagonist MK-801, but not the administration of the ßAR antagonist propranolol, when given in conjunction with memory reactivation. CONCLUSIONS: As for natural reinforcers, NMDARs are required for the reconsolidation of all aspects of pavlovian drug memories, but ßARs are only required for the memory representation underlying conditioned reinforcement. These results indicate the potential utility of treatments based upon disrupting cue-drug memory reconsolidation in preventing relapse.