9th London - Innsbruck colloquium on status epilepticus and acute seizures, held in London in April 2024.

This editorial introduces the Epilepsy & Behavior issue devoted to the 9th London-Innsbruck Colloquium on Status Epilepticus. It summarises the topics of the colloquium and other aspects. The selection of the presentations made in the special issue give a flavour of recent progress and development in the field.

Drug repurposing in status epilepticus.

The treatment of status epilepticus (SE) has changed little in the last 20 years, largely because of the high risks and costs of new drug development for SE. Moreover, SE poses specific challenges to drug development, such as patient diversity, logistical hurdles, and the need for acute treatment strategies that differ from chronic seizure prevention. This has reduced the appetite of industry to develop new drugs in this area. Drug repurposing is an attractive approach to address this unmet need. It offers significant advantages, including reduced development time, lower costs, and higher success rates, compared to novel drug development. Here I demonstrate how novel methods integrating biological knowledge and computational methods can be applied to drug repurposing in status epilepticus. Biological approaches focus on addressing mechanisms underlying drug resistance in SE (using for example ketamine, tacrolimus and safinamide) and longer-term consequences (using for example omaveloxolone, celecoxib and losartan). Additionally, artificial intelligence platforms, such as ChatGPT, can rapidly generate promising drug lists, while in silico methods can analyze gene expression changes to predict molecular targets. Combining AI and in silico approaches has identified several candidate drugs, including metformin, sirolimus and riluzole, for SE treatment. Despite the promise of repurposing, challenges remain, such as intellectual property issues and regulatory barriers. Nonetheless, drug repurposing presents a viable solution to the high costs and slow progress of traditional drug development for SE. This paper is based on a presentation made at the 9th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures, in April 2024.

Tactile sensitivity alters textile touch perception.

Tactility plays a crucial role in our interactions with the physical world including our ability to differentiate textile textures and their associated comfort. There is an increasing focus on digitally interactive haptic experiences enabling consumers to feel virtual objects realistically. This could revolutionize how we experience textiles in e-commerce platform, virtual and augmented reality, and shape the future of textiles in the metaverse. In this study, we examined the impact of tactile sensitivity on touch perception of a large nonhomogeneous sample of 22 textile swatches. The tactile sensitivity was studied using four factors: assessors' "subject-matter expertise", "frequency of performing handiwork", "frequency of working with textiles", and "familiarity of textile textures". The participants noted their tactile assessment of eight touch attributes of textile swatches on a 5-point Likert scale. Through predictive modeling, we analyzed the effect of tactile sensitivity on participants' tactile assessment scores. Our key findings revealed that participants' tactile sensitivity significantly influenced their perception of the textile textures. Notably, the "frequency of working with textiles" had the most substantial impact on participants' tactile ratings followed by their familiarity with textile textures. Interestingly, the perceptual differences of isotropy attribute were significant in all the cases. Overall, there was no significant difference in the tactile ratings between textile experts and non-experts, except for nine occurrences, four of which were related to perceptual differences in roughness of the woven fabrics. Conversely, the two groups had no statistically significant differences at all in their perceptions of hairiness, scratchiness, and uniformity.

Neuronal oscillations in cognition: Down syndrome as a model of mouse to human translation.

Down syndrome (DS), a prevalent cognitive disorder resulting from trisomy of human chromosome 21 (Hsa21), poses a significant global health concern. Affecting approximately 1 in 800 live births worldwide, DS is the leading genetic cause of intellectual disability and a major predisposing factor for early-onset Alzheimer's dementia. The estimated global population of individuals with DS is 6 million, with increasing prevalence due to advances in DS health care. Global efforts are dedicated to unraveling the mechanisms behind the varied clinical outcomes in DS. Recent studies on DS mouse models reveal disrupted neuronal circuits, providing insights into DS pathologies. Yet, translating these findings to humans faces challenges due to limited systematic electrophysiological analyses directly comparing human and mouse. Additionally, disparities in experimental procedures between the two species pose hurdles to successful translation. This review provides a concise overview of neuronal oscillations in human and rodent cognition. Focusing on recent DS mouse model studies, we highlight disruptions in associated brain function. We discuss various electrophysiological paradigms and suggest avenues for exploring molecular dysfunctions contributing to DS-related cognitive impairments. Deciphering neuronal oscillation intricacies holds promise for targeted therapies to alleviate cognitive disabilities in DS individuals.

NAD metabolism and heart failure: Mechanisms and therapeutic potentials.

Nicotinamide adenine dinucleotide provides the critical redox pair, NAD+ and NADH, for cellular energy metabolism. In addition, NAD+ is the precursor for de novo NADP+ synthesis as well as the co-substrates for CD38, poly(ADP-ribose) polymerase and sirtuins, thus, playing a central role in the regulation of oxidative stress and cell signaling. Declines of the NAD+ level and altered NAD+/NADH redox states have been observed in cardiometabolic diseases of various etiologies. NAD based therapies have emerged as a promising strategy to treat cardiovascular disease. Strategies that reduce NAD+ consumption or promote NAD+ production have repleted intracellular NAD+ or normalized NAD+/NADH redox in preclinical studies. These interventions have shown cardioprotective effects in multiple models suggesting a great promise of the NAD+ elevating therapy. Mechanisms for the benefit of boosting NAD+ level, however, remain incompletely understood. Moreover, despite the robust pre-clinical studies there are still challenges to translate the therapy to clinic. Here, we review the most up to date literature on mechanisms underlying the NAD+ elevating interventions and discuss the progress of human studies. We also aim to provide a better understanding of how NAD metabolism is changed in failing hearts with a particular emphasis on types of strategies employed and methods to target these pathways. Finally, we conclude with a comprehensive assessment of the challenges in developing NAD-based therapies for heart diseases, and to provide a perspective on the future of the targeting strategies.

Functional seizures and their mimics: a retrospective service review of cases from a tertiary video telemetry database.

Objective: Identify the proportion of patients referred with putative functional seizures (FS) that were subsequently re-diagnosed as epileptic seizures (ES), or an alternative diagnosis, following video telemetry EEG (VTEEG). In addition, describe the characteristics of those seizures. Methods: The VTEEG reports from patients admitted to the Chalfont Centre for Epilepsy between 2019 and 2022 were reviewed. Pre-VTEEG and post-VTEEG diagnoses were compared to identify whether a diagnostic revision was made from suspected FS to ES or another diagnosis. Diagnostic revision cases were then grouped into cohorts with associated features and reviewed to characterise and describe FS mimics. Results: 444 VTEEG reports where patients had habitual events were identified. 4.7% of patients were referred with FS and were subsequently diagnosed with ES or another diagnosis. In this group, several cohorts could be identified including frontal lobe epileptic seizures, ES with functional overlay, insular or temporal lobe epileptic seizures associated with autonomic or marked experiential peri-ictal symptoms, and individuals who had both ES and FS but whose ES were revealed on medication withdrawal. Conclusion: In patients referred to a tertiary epilepsy unit, a small minority of cases had seizures diagnosed as functional and reclassified as epileptic or an alternative diagnosis. It is clinically important to be aware of these FS mimics.

No Difference in 10-year Clinical or Radiographic Outcomes Between Kinematic and Mechanical Alignment in TKA: A Randomized Trial.

BACKGROUND: There is continuing debate about the ideal philosophy for component alignment in TKA. However, there are limited long-term functional and radiographic data on randomized comparisons of kinematic alignment versus mechanical alignment. QUESTIONS/PURPOSES: We present the 10-year follow-up findings of a single-center, multisurgeon randomized controlled trial (RCT) comparing these two alignment philosophies in terms of the following questions: (1) Is there a difference in PROM scores? (2) Is there a difference in survivorship free from revision or reoperation for any cause? (3) Is there a difference in survivorship free from radiographic loosening? METHODS: Ninety-nine patients undergoing primary TKA for osteoarthritis were randomized to either the mechanical alignment (n = 50) or kinematic alignment (n = 49) group. Eligibility for the study was patients undergoing unilateral TKA for osteoarthritis who were suitable for a cruciate-retaining TKA and could undergo MRI. Patients who had previous osteotomy, coronal alignment > 15° from neutral, a fixed flexion deformity > 15°, or instability whereby constrained components were being considered were excluded. Computer navigation was used in the mechanical alignment group, and patient-specific cutting blocks were used in the kinematic alignment group. At 10 years, 86% (43) of the patients in the mechanical alignment group and 80% (39) in the kinematic alignment group were available for follow-up performed as a per-protocol analysis. The PROMs that we assessed included the Knee Society Score, Oxford Knee Score, WOMAC, Forgotten Joint Score, and EuroQol 5-Dimension score. Kaplan-Meier analysis was used to assess survivorship free from reoperation (any reason) and revision (change or addition of any component). A single blinded observer assessed radiographs for signs of aseptic loosening (as defined by the presence of progressive radiolucent lines in two or more zones), which was reported as survivorship free from loosening. RESULTS: At 10 years, there was no difference in any PROM score measured between the groups. Ten-year survivorship free from revision (components removed or added) likewise did not differ between the groups (96% [95% CI 91% to 99%] for the mechanical alignment group and 91% [95% CI 83% to 99%] for the kinematic alignment group; p = 0.38). There were two revisions in the mechanical alignment group (periprosthetic fracture, deep infection) and four in the kinematic alignment group (two secondary patella resurfacings, two deep infections). There was no statistically significant difference in reoperations for any cause between the two groups. There was no difference with regard to survivorship free from loosening on radiographic review (χ2 = 1.3; p = 0.52) (progressive radiolucent lines seen at 10 years were 0% for mechanical alignment and 3% for kinematic alignment). CONCLUSION: Like the 2-year and 5-year outcomes previously reported, 10-year follow-up for this RCT demonstrated no functional or radiographic difference in outcomes between mechanical alignment and kinematic alignment TKA. Anticipated functional benefits of kinematic alignment were not demonstrated, and revision-free survivorship at 10 years did not differ between the two groups. Given the unknown long-term impact of kinematic alignment with regard to implant position (especially tibial component varus), we must conclude that mechanical alignment remains the reference standard for TKA. We could not demonstrate any advantage to kinematic alignment at 10-year follow-up. LEVEL OF EVIDENCE: Level I, therapeutic study.

Manganese-Catalyzed Synthesis of Polyketones Using Hydrogen-Borrowing Approach.

We report here a method of making polyketones from the coupling of diketones and diols using a manganese pincer complex. The methodology allows us to access various polyketones (polyarylalkylketone) containing aryl, alkyl, and ether functionalities, bridging the gap between the two classes of commercially available polyketones: aliphatic polyketones and polyaryletherketones. Using this methodology, 12 polyketones have been synthesized and characterized using various analytical techniques to understand their chemical, physical, morphological, and mechanical properties. Based on previous reports and our studies, we suggest that the polymerization occurs via a hydrogen-borrowing mechanism that involves the dehydrogenation of diols to dialdehyde followed by aldol condensation of dialdehyde with diketones to form chalcone derivatives and their subsequent hydrogenation to form polyarylalkylketones.

GENETIC AND TRAIT VARIABILITY OF GYRINICOLA REVEALS THE EXISTENCE OF AT LEAST FOUR SPECIES WITHIN THE UNITED STATES.

The tadpole-dwelling pinworm, Gyrinicola batrachiensis (Walton, 1929) Adamson, 1981 was recognized as the sole representative of the genus across Canada and the United States. However, evaluation of the morphology of these parasites across their range revealed considerable morphological variability that suggested diagnosable morphotypes. These morphotypes were associated with different species of anurans, several of which occurred in sympatry. Herein we use an extensive geographic sampling across the United States to obtain the morphotypes, screen their genetic diversity, and analyze this information using an integrative approach. We reconstructed their phylogeny using nuclear ribosomal partial genes 18S and 28S, ITS1, 5.8S, and ITS2, as well as 5 mitochondrial genes generated with Next-Generation sequencing technology. This phylogeny reveals 3 well-resolved lineages, which upon the use of a statistical approach (bPTP [Bayesian implementation of the Poisson tree processes]) supports the delimitation of 4 distinct groups equivalent to species. These putative species groups were tested using morphological characteristics paired with a MANOVA and canonical variate analysis. Results suggest that at least 4 species of Gyrinicola are present within North America, resulting in the resurrection of G. armatus (Walton, 1933) and the description of 2 new species.

The new science of sleep: From cells to large-scale societies.

In the past 20 years, more remarkable revelations about sleep and its varied functions have arguably been made than in the previous 200. Building on this swell of recent findings, this essay provides a broad sampling of selected research highlights across genetic, molecular, cellular, and physiological systems within the body, networks within the brain, and large-scale social dynamics. Based on this raft of exciting new discoveries, we have come to realize that sleep, in this moment of its evolution, is very much polyfunctional (rather than monofunctional), yet polyfunctional for reasons we had never previously considered. Moreover, these new polyfunctional insights powerfully reaffirm sleep as a critical biological, and thus health-sustaining, requisite. Indeed, perhaps the only thing more impressive than the unanticipated nature of these newly emerging sleep functions is their striking divergence, from operations of molecular mechanisms inside cells to entire group societal dynamics.

Enhancing chondrogenic differentiation of mesenchymal stem cells through synergistic effects of cellulose nanocrystals and plastic compression in collagen-based hydrogel for cartilage formation.

Collagen-based (COL) hydrogels could be a promising treatment option for injuries to the articular cartilage (AC) becuase of their similarity to AC native extra extracellular matrix. However, the high hydration of COL hydrogels poses challenges for AC's mechanical properties. To address this, we developed a hydrogel platform that incorporating cellulose nanocrystals (CNCs) within COL and followed by plastic compression (PC) procedure to expel the excessive fluid out. This approach significantly improved the mechanical properties of the hydrogels and enhanced the chondrogenic differentiation of mesenchymal stem cells (MSCs). Radially confined PC resulted in higher collagen fibrillar densities together with reducing fibril-fibril distances. Compressed hydrogels containing CNCs exhibited the highest compressive modulus and toughness. MSCs encapsulated in these hydrogels were initially affected by PC, but their viability improved after 7 days. Furthermore, the morphology of the cells and their secretion of glycosaminoglycans (GAGs) were positively influenced by the compressed COL-CNC hydrogel. Our findings shed light on the combined effects of PC and CNCs in improving the physical and mechanical properties of COL and their role in promoting chondrogenesis.

5-HTP inhibits eosinophilia via intracellular endothelial 5-HTRs; SNPs in 5-HTRs associate with asthmatic lung function.

Background: Previous research showed that 5-hydroxytryptophan (5HTP), a metabolic precursor of serotonin, reduces allergic lung inflammation by inhibiting eosinophil migration across endothelial monolayers. Objective: It is unknown if serotonin receptors are involved in mediating this 5HTP function or if serotonin receptor (HTR) single nucleotide polymorphisms (SNPs) associate with lung function in humans. Methods: Serotonin receptor subtypes were assessed by qPCR, western blot, confocal microscopy, pharmacological inhibitors and siRNA knockdown. HTR SNPs were assessed in two cohorts. Results: Pharmacological inhibition or siRNA knockdown of the serotonin receptors HTR1A or HTR1B in endothelial cells abrogated the inhibitory effects of 5HTP on eosinophil transendothelial migration. In contrast, eosinophil transendothelial migration was not inhibited by siRNA knockdown of HTR1A or HTR1B in eosinophils. Surprisingly, these HTRs were intracellular in endothelial cells and an extracellular supplementation with serotonin did not inhibit eosinophil transendothelial migration. This is consistent with the inability of serotonin to cross membranes, the lack of selective serotonin reuptake receptors on endothelial cells, and the studies showing minimal impact of selective serotonin reuptake inhibitors on asthma. To extend our HTR studies to humans with asthma, we examined the CHIRAH and GALA cohorts for HTR SNPs that affect HTR function or are associated with behavior disorders. A polygenic index of SNPs in HTRs was associated with lower lung function in asthmatics. Conclusions: Serotonin receptors mediate 5HTP inhibition of transendothelial migration and HTR SNPs associate with lower lung function. These results may serve to aid in design of novel interventions for allergic inflammation.

Structural connectivity changes in unilateral hearing loss.

Network connectivity, as mapped by the whole brain connectome, plays a crucial role in regulating auditory function. Auditory deprivation such as unilateral hearing loss might alter structural network connectivity; however, these potential alterations are poorly understood. Thirty-seven acoustic neuroma patients with unilateral hearing loss (19 left-sided and 18 right-sided) and 19 healthy controls underwent diffusion-weighted and T1-weighted imaging to assess edge strength, node strength, and global efficiency of the structural connectome. Edge strength was estimated by pair-wise normalized streamline density from tractography and connectomics. Node strength and global efficiency were calculated through graph theory analysis of the connectome. Pure-tone audiometry and word recognition scores were used to correlate the degree and duration of unilateral hearing loss with node strength and global efficiency. We demonstrate significantly stronger edge strength and node strength through the visual network, weaker edge strength and node strength in the somatomotor network, and stronger global efficiency in the unilateral hearing loss patients. No discernible correlations were observed between the degree and duration of unilateral hearing loss and the measures of node strength or global efficiency. These findings contribute to our understanding of the role of structural connectivity in hearing by facilitating visual network upregulation and somatomotor network downregulation after unilateral hearing loss.

Abundances of Neutron-capture Elements in 62 Stars in the Globular Cluster Messier 15.

M15 is a globular cluster with a known spread in neutron-capture elements. This paper presents abundances of neutron-capture elements for 62 stars in M15. Spectra were obtained with the Michigan/Magellan Fiber System spectrograph, covering a wavelength range from ∼4430 to 4630 Å. Spectral lines from Fe i, Fe ii, Sr i, Zr ii, Ba ii, La ii, Ce ii, Nd ii, Sm ii, Eu ii, and Dy ii were measured, enabling classifications and neutron-capture abundance patterns for the stars. Of the 62 targets, 44 are found to be highly Eu-enhanced r-II stars, another 17 are moderately Eu-enhanced r-I stars, and one star is found to have an s-process signature. The neutron-capture patterns indicate that the majority of the stars are consistent with enrichment by the r-process. The 62 target stars are found to show significant star-to-star spreads in Sr, Zr, Ba, La, Ce, Nd, Sm, Eu, and Dy, but no significant spread in Fe. The neutron-capture abundances are further found to have slight correlations with sodium abundances from the literature, unlike what has been previously found; follow-up studies are needed to verify this result. The findings in this paper suggest that the Eu-enhanced stars in M15 were enhanced by the same process, that the nucleosynthetic source of this Eu pollution was the r-process, and that the r-process source occurred as the first generation of cluster stars was forming.

Estimating the likelihood of epilepsy from clinically noncontributory electroencephalograms using computational analysis: A retrospective, multisite case-control study.

OBJECTIVE: This study was undertaken to validate a set of candidate biomarkers of seizure susceptibility in a retrospective, multisite case-control study, and to determine the robustness of these biomarkers derived from routinely collected electroencephalography (EEG) within a large cohort (both epilepsy and common alternative conditions such as nonepileptic attack disorder). METHODS: The database consisted of 814 EEG recordings from 648 subjects, collected from eight National Health Service sites across the UK. Clinically noncontributory EEG recordings were identified by an experienced clinical scientist (N = 281; 152 alternative conditions, 129 epilepsy). Eight computational markers (spectral [n = 2], network-based [n = 4], and model-based [n = 2]) were calculated within each recording. Ensemble-based classifiers were developed using a two-tier cross-validation approach. We used standard regression methods to assess whether potential confounding variables (e.g., age, gender, treatment status, comorbidity) impacted model performance. RESULTS: We found levels of balanced accuracy of 68% across the cohort with clinically noncontributory normal EEGs (sensitivity =61%, specificity =75%, positive predictive value =55%, negative predictive value =79%, diagnostic odds ratio =4.64, area under receiver operated characteristics curve =.72). Group level analysis found no evidence suggesting any of the potential confounding variables significantly impacted the overall performance. SIGNIFICANCE: These results provide evidence that the set of biomarkers could provide additional value to clinical decision-making, providing the foundation for a decision support tool that could reduce diagnostic delay and misdiagnosis rates. Future work should therefore assess the change in diagnostic yield and time to diagnosis when utilizing these biomarkers in carefully designed prospective studies.

Hippocampus diffusivity abnormalities in classical trigeminal neuralgia.

Introduction: Patients with chronic pain frequently report cognitive symptoms that affect memory and attention, which are functions attributed to the hippocampus. Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder characterized by paroxysmal attacks of unilateral orofacial pain. Given the stereotypical nature of TN pain and lack of negative symptoms including sensory loss, TN provides a unique model to investigate the hippocampal implications of chronic pain. Recent evidence demonstrated that TN is associated with macrostructural hippocampal abnormalities indicated by reduced subfield volumes; however, there is a paucity in our understanding of hippocampal microstructural abnormalities associated with TN. Objectives: To explore diffusivity metrics within the hippocampus, along with its functional and structural subfields, in patients with TN. Methods: To examine hippocampal microstructure, we utilized diffusion tensor imaging in 31 patients with TN and 21 controls. T1-weighted magnetic resonance images were segmented into hippocampal subfields and registered into diffusion-weighted imaging space. Fractional anisotropy (FA) and mean diffusivity were extracted for hippocampal subfields and longitudinal axis segmentations. Results: Patients with TN demonstrated reduced FA in bilateral whole hippocampi and hippocampal body and contralateral subregions CA2/3 and CA4, indicating microstructural hippocampal abnormalities. Notably, patients with TN showed significant correlation between age and hippocampal FA, while controls did not exhibit this correlation. These effects were driven chiefly by female patients with TN. Conclusion: This study demonstrates that TN is associated with microstructural hippocampal abnormalities, which may precede and potentially be temporally linked to volumetric hippocampal alterations demonstrated previously. These findings provide further evidence for the role of the hippocampus in chronic pain and suggest the potential for targeted interventions to mitigate cognitive symptoms in patients with chronic pain.

Quantitative Time-of-Flight Head Magnetic Resonance Angiography of Cerebrovascular Disease.

BACKGROUND: Standard Cartesian time-of-flight (TOF) head magnetic resonance angiography (MRA) is routinely used to evaluate the intracranial arteries, but does not provide quantitative hemodynamic information that is useful for patient risk stratification as well as for monitoring treatment and tracking changes in blood flow over time. Quantitative TOF (qTOF) MRA represents a new and efficient method for simultaneous evaluating the intracranial arteries and quantifying blood flow velocity, but it has not yet been evaluated in patients with cerebrovascular disease. PURPOSE: To evaluate qTOF for simultaneously evaluating the intracranial arteries and quantifying intracranial blood flow velocity in patients with cerebrovascular disease, without the need for a phase contrast (PC) scan. STUDY TYPE: Prospective. SUBJECTS: Twenty-four patients (18 female, 6 male) with cerebrovascular disease. FIELD STRENGTH/SEQUENCES: Head MRA at 3 T using gradient-echo 3D qTOF, standard Cartesian TOF, and PC protocols. ASSESSMENT: Three independent readers assessed arterial image quality using a 4-point scale (1: non-diagnostic, 4: excellent) and artifact presence. Total and component flow velocities obtained with qTOF and PC were measured. STATISTICAL TESTS: Wilcoxon signed-rank tests, Gwet's AC2, intraclass correlation coefficients (ICC) for absolute agreement, Bland-Altman analyses, tests of equal proportions. P values <0.05 were considered statistically significant. RESULTS: Averaged across readers and compared to standard Cartesian TOF, qTOF significantly improved overall arterial image quality (3.8 ± 0.2 vs. 3.6 ± 0.5), image quality at locations of pathology (3.7 ± 0.5 vs. 3.4 ± 0.7), and increased the proportion of evaluations rated without artifacts (63.9% [46/72] vs. 37.5% [27/72]). qTOF significantly agreed with PC for total flow velocity (ICC = 0.71) and component flow velocity (ICC = 0.89). DATA CONCLUSION: qTOF angiography of the head matched or improved upon the image quality of standard Cartesian TOF, reduced image artifacts, and provided quantitative hemodynamic data, without the need for a PC scan. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Sequential deep learning image enhancement models improve diagnostic confidence, lesion detectability, and image reconstruction time in PET.

BACKGROUND: Investigate the potential benefits of sequential deployment of two deep learning (DL) algorithms namely DL-Enhancement (DLE) and DL-based time-of-flight (ToF) (DLT). DLE aims to enhance the rapidly reconstructed ordered-subset-expectation-maximisation algorithm (OSEM) images towards block-sequential-regularised-expectation-maximisation (BSREM) images, whereas DLT aims to improve the quality of BSREM images reconstructed without ToF. As the algorithms differ in their purpose, sequential application may allow benefits from each to be combined. 20 FDG PET-CT scans were performed on a Discovery 710 (D710) and 20 on Discovery MI (DMI; both GE HealthCare). PET data was reconstructed using five combinations of algorithms:1. ToF-BSREM, 2. ToF-OSEM + DLE, 3. OSEM + DLE + DLT, 4. ToF-OSEM + DLE + DLT, 5. ToF-BSREM + DLT. To assess image noise, 30 mm-diameter spherical VOIs were drawn in both lung and liver to measure standard deviation of voxels within the volume. In a blind clinical reading, two experienced readers rated the images on a five-point Likert scale based on lesion detectability, diagnostic confidence, and image quality. RESULTS: Applying DLE + DLT reduced noise whilst improving lesion detectability, diagnostic confidence, and image reconstruction time. ToF-OSEM + DLE + DLT reconstructions demonstrated an increase in lesion SUVmax of 28 ± 14% (average ± standard deviation) and 11 ± 5% for data acquired on the D710 and DMI, respectively. The same reconstruction scored highest in clinical readings for both lesion detectability and diagnostic confidence for D710. CONCLUSIONS: The combination of DLE and DLT increased diagnostic confidence and lesion detectability compared to ToF-BSREM images. As DLE + DLT used input OSEM images, and because DL inferencing was fast, there was a significant decrease in overall reconstruction time. This could have applications to total body PET.

Status epilepticus: what's new for the intensivist.

PURPOSE OF REVIEW: Status epilepticus (SE) is a common neurologic emergency affecting about 36.1/100 000 person-years that frequently requires intensive care unit (ICU) admission. There have been advances in our understanding of epidemiology, pathophysiology, and EEG monitoring of SE, and there have been large-scale treatment trials, discussed in this review. RECENT FINDINGS: Recent changes in the definitions of SE have helped guide management protocols and we have much better predictors of outcome. Observational studies have confirmed the efficacy of benzodiazepines and large treatment trials indicate that all routinely used second line treatments (i.e., levetiracetam, valproate and fosphenytoin) are equally effective. Better understanding of the pathophysiology has indicated that nonanti-seizure medications aimed at underlying pathological processes should perhaps be considered in the treatment of SE; already immunosuppressant treatments are being more widely used in particular for new onset refractory status epilepticus (NORSE) and Febrile infection-related epilepsy syndrome (FIRES) that sometimes revealed autoimmune or paraneoplastic encephalitis. Growing evidence for ICU EEG monitoring and major advances in automated analysis of the EEG could help intensivist to assess the control of electrographic seizures. SUMMARY: Research into the morbi-mortality of SE has highlighted the potential devastating effects of this condition, emphasizing the need for rapid and aggressive treatment, with particular attention to cardiorespiratory and neurological complications. Although we now have a good evidence-base for the initial status epilepticus management, the best treatments for the later stages are still unclear and clinical trials of potentially disease-modifying therapies are long overdue.