The seizure severity score: a quantitative tool for comparing seizures and their response to therapy.

Objective.Epilepsy is a neurological disorder characterized by recurrent seizures which vary widely in severity, from clinically silent to prolonged convulsions. Measuring severity is crucial for guiding therapy, particularly when complete control is not possible. Seizure diaries, the current standard for guiding therapy, are insensitive to the duration of events or the propagation of seizure activity across the brain. We present a quantitative seizure severity score that incorporates electroencephalography (EEG) and clinical data and demonstrate how it can guide epilepsy therapies.Approach.We collected intracranial EEG and clinical semiology data from 54 epilepsy patients who had 256 seizures during invasive, in-hospital presurgical evaluation. We applied an absolute slope algorithm to EEG recordings to identify seizing channels. From this data, we developed a seizure severity score that combines seizure duration, spread, and semiology using non-negative matrix factorization. For validation, we assessed its correlation with independent measures of epilepsy burden: seizure types, epilepsy duration, a pharmacokinetic model of medication load, and response to epilepsy surgery. We investigated the association between the seizure severity score and preictal network features.Main results.The seizure severity score augmented clinical classification by objectively delineating seizure duration and spread from recordings in available electrodes. Lower preictal medication loads were associated with higher seizure severity scores (p= 0.018, 97.5% confidence interval = [-1.242, -0.116]) and lower pre-surgical severity was associated with better surgical outcome (p= 0.042). In 85% of patients with multiple seizure types, greater preictal change from baseline was associated with higher severity.Significance.We present a quantitative measure of seizure severity that includes EEG and clinical features, validated on gold standard in-patient recordings. We provide a framework for extending our tool's utility to ambulatory EEG devices, for linking it to seizure semiology measured by wearable sensors, and as a tool to advance data-driven epilepsy care.

Response-Adapted Therapy for Newly Diagnosed Multiple Myeloma.

PURPOSE OF REVIEW: The development of potent novel agents has improved outcomes for patients with multiple myeloma (MM). Heterogeneity of response to therapy, an expanding arsenal of treatment options, and cost are however major challenges for physicians making treatment decisions. Response-adapted therapy is hence an attractive strategy for sequencing of therapy in MM. Despite its successful application in other haematologic malignancies, response-adapted therapy is yet to become a standard of care for MM. We provide our perspective on response-adapted therapeutic strategies evaluated thus far and how they may be implemented and improved on in treatment algorithms of the future. RECENT FINDINGS: While older studies suggested that early response based on International Myeloma Working Group response criteria could impact long-term outcomes, recent data have contradicted these findings. The advent of minimal residual disease (MRD) as a powerful prognostic factor in MM has raised the promise of MRD-adapted treatment strategies. The development of more sensitive techniques for paraprotein quantification as well as imaging modalities to detect extramedullary disease is likely to change response assessment in MM. These techniques combined with MRD assessment may provide sensitive and holistic response assessments which could be evaluated in clinical trials. Response-adapted treatment algorithms have the potential to allow an individualised treatment strategy, maximising efficacy, while minimising toxicities and cost. Standardisation of MRD methodology, incorporation of imaging into response assessment, and the optimal management of MRD positive patients are key questions to be addressed in future trials.

Mechanisms, Effects, and Management of Neurological Complications of Post-Acute Sequelae of COVID-19 (NC-PASC).

With a growing number of patients entering the recovery phase following infection with SARS-CoV-2, understanding the long-term neurological consequences of the disease is important to their care. The neurological complications of post-acute sequelae of SARS-CoV-2 infection (NC-PASC) represent a myriad of symptoms including headaches, brain fog, numbness/tingling, and other neurological symptoms that many people report long after their acute infection has resolved. Emerging reports are being published concerning COVID-19 and its chronic effects, yet limited knowledge of disease mechanisms has challenged therapeutic efforts. To address these issues, we review broadly the literature spanning 2020-2022 concerning the proposed mechanisms underlying NC-PASC, outline the long-term neurological sequelae associated with COVID-19, and discuss potential clinical interventions.

Quantitative approaches to guide epilepsy surgery from intracranial EEG.

Over the past 10 years, the drive to improve outcomes from epilepsy surgery has stimulated widespread interest in methods to quantitatively guide epilepsy surgery from intracranial EEG (iEEG). Many patients fail to achieve seizure freedom, in part due to the challenges in subjective iEEG interpretation. To address this clinical need, quantitative iEEG analytics have been developed using a variety of approaches, spanning studies of seizures, interictal periods, and their transitions, and encompass a range of techniques including electrographic signal analysis, dynamical systems modeling, machine learning and graph theory. Unfortunately, many methods fail to generalize to new data and are sensitive to differences in pathology and electrode placement. Here, we critically review selected literature on computational methods of identifying the epileptogenic zone from iEEG. We highlight shared methodological challenges common to many studies in this field and propose ways that they can be addressed. One fundamental common pitfall is a lack of open-source, high-quality data, which we specifically address by sharing a centralized high-quality, well-annotated, multicentre dataset consisting of >100 patients to support larger and more rigorous studies. Ultimately, we provide a road map to help these tools reach clinical trials and hope to improve the lives of future patients.

Normative intracranial EEG maps epileptogenic tissues in focal epilepsy.

Planning surgery for patients with medically refractory epilepsy often requires recording seizures using intracranial EEG. Quantitative measures derived from interictal intracranial EEG yield potentially appealing biomarkers to guide these surgical procedures; however, their utility is limited by the sparsity of electrode implantation as well as the normal confounds of spatiotemporally varying neural activity and connectivity. We propose that comparing intracranial EEG recordings to a normative atlas of intracranial EEG activity and connectivity can reliably map abnormal regions, identify targets for invasive treatment and increase our understanding of human epilepsy. Merging data from the Penn Epilepsy Center and a public database from the Montreal Neurological Institute, we aggregated interictal intracranial EEG retrospectively across 166 subjects comprising >5000 channels. For each channel, we calculated the normalized spectral power and coherence in each canonical frequency band. We constructed an intracranial EEG atlas by mapping the distribution of each feature across the brain and tested the atlas against data from novel patients by generating a z-score for each channel. We demonstrate that for seizure onset zones within the mesial temporal lobe, measures of connectivity abnormality provide greater distinguishing value than univariate measures of abnormal neural activity. We also find that patients with a longer diagnosis of epilepsy have greater abnormalities in connectivity. By integrating measures of both single-channel activity and inter-regional functional connectivity, we find a better accuracy in predicting the seizure onset zones versus normal brain (area under the curve = 0.77) compared with either group of features alone. We propose that aggregating normative intracranial EEG data across epilepsy centres into a normative atlas provides a rigorous, quantitative method to map epileptic networks and guide invasive therapy. We publicly share our data, infrastructure and methods, and propose an international framework for leveraging big data in surgical planning for refractory epilepsy.

Proposed Quality Performance Indicators (QPI's) for axillary lymphadenectomy in metastatic cutaneous melanoma.

INTRODUCTION: Axillary lymph node clearance (ALNC) continues to play a central role in the management of melanoma. However, what defines an adequate lymphadenectomy remains unclear. We aimed to propose Quality Performance Indicators (QPIs) for ALNC and to determine if the number of lymph nodes (LNs) removed impacts survival. METHODS: We reviewed patients who underwent ALNC for melanoma at the Waitemata District Health Board and Melanoma Unit between February 2005 and October 2019, performed by two surgeons with standardized technique and surveillance. RESULTS: 105 patients with stage III melanoma were included, of which 73 had clinically evident disease and 32 had clinically occult disease. The mean total number of LNs excised was 29 (SD 10.90, range 10-76). On multivariate analysis, lymph node ratio (HR 4.48, 95% CI 1.55-12.93, p = 0.006), extracapsular spread (HR 2.53, 95% CI 1.06-6.05, p = 0.036) and distant recurrence (HR 11.24, 95% CI 3.79-33.31, p < 0.001) were significant predictors of mortality. The number of LNs removed did not predict survival outcomes, while the lymph node ratio did significantly predict survival outcomes. The regional recurrence rate was 3.8%. DISCUSSION: We propose that QPIs for ALNC in melanoma include a 90th percentile LN yield of greater than 15, a mean LN yield of 20, a regional recurrence rate of less than 10%, and an overall complication rate of less than 50%. CONCLUSION: The establishment of QPIs can help ensure that surgical oncology patients receive the highest quality of care.

Electrocorticography and stereo EEG provide distinct measures of brain connectivity: implications for network models.

Brain network models derived from graph theory have the potential to guide functional neurosurgery, and to improve rates of post-operative seizure freedom for patients with epilepsy. A barrier to applying these models clinically is that intracranial EEG electrode implantation strategies vary by centre, region and country, from cortical grid & strip electrodes (Electrocorticography), to purely stereotactic depth electrodes (Stereo EEG), to a mixture of both. To determine whether models derived from one type of study are broadly applicable to others, we investigate the differences in brain networks mapped by electrocorticography and stereo EEG in a cohort of patients who underwent surgery for temporal lobe epilepsy and achieved a favourable outcome. We show that networks derived from electrocorticography and stereo EEG define distinct relationships between resected and spared tissue, which may be driven by sampling bias of temporal depth electrodes in patients with predominantly cortical grids. We propose a method of correcting for the effect of internodal distance that is specific to electrode type and explore how additional methods for spatially correcting for sampling bias affect network models. Ultimately, we find that smaller surgical targets tend to have lower connectivity with respect to the surrounding network, challenging notions that abnormal connectivity in the epileptogenic zone is typically high. Our findings suggest that effectively applying computational models to localize epileptic networks requires accounting for the effects of spatial sampling, particularly when analysing both electrocorticography and stereo EEG recordings in the same cohort, and that future network studies of epilepsy surgery should also account for differences in focality between resection and ablation. We propose that these findings are broadly relevant to intracranial EEG network modelling in epilepsy and an important step in translating them clinically into patient care.

Judicious utilization of healthcare resources: reducing unindicated pediatric anaerobic blood cultures in a pediatric hospital.

The decline in anaerobic infections in the past 15 years has resulted in healthcare professionals questioning the need for routine anaerobic blood cultures. In this study, we extracted baseline aerobic and anaerobic blood culture rates over the past 10 years (2001-2010) from our pediatric wards. A questionnaire survey of doctors was conducted to gather their views regarding anaerobic blood cultures. Interventions such as physician education were introduced over 6 months to reduce unindicated anaerobic blood cultures. Furthermore, the rates of blood cultures were tracked over time after intervention. Before intervention, 85% of doctors surveyed routinely ordered anaerobic blood cultures, 90% were unaware of any guidelines for anaerobic blood cultures, and 100% were unaware of the costs. The combination of physician education and restrictive interventions resulted in an 80% reduction in the number of anaerobic blood cultures performed and processed, which translated into savings of USD $2,883 per week, with projected savings of USD $145,560 annually.

Meta-analysis of intermittent Pringle manoeuvre versus no Pringle manoeuvre in elective liver surgery.

BACKGROUND AND OBJECTIVES: Intermittent Pringle manoeuvre (IPM) is frequently used during liver surgery. This meta-analysis aimed to review the impact on blood loss, operating time and morbidity and mortality with and without use of IPM. METHODS: An electronic search was performed of the MEDLINE, EMBASE, PubMed databases using both subject headings (MeSH) and truncated word searches to identify all articles published that related to this topic. Pooled risk ratios were calculated for categorical outcomes, and mean differences (MDs) for secondary continuous outcomes, using the fixed-effects and random-effects models for meta-analysis. RESULTS: Four randomized controlled trials encompassing 392 patients were analysed to achieve a summated outcome. Pooled data analysis showed the use of IPM resulted in reduced transection time/cm(2) (MD -0.53 (-0.88, -0.18) min/cm(2) (P = 0.003)) but with comparable blood loss (mL/cm(2)) (MD -1.67 (-4.41, 1.08) mL/cm(2), P = 0.23), overall blood loss (MD -20.42 (-89.42, 48.58) mL), blood transfusion requirements (risk ratio 0.78 (0.40, 1.52, P = 0.47)) and morbidity and mortality compared to no Pringle manoeuvre. In addition, there was no significant difference in the post-operative hospital stay (MD 0.37 (-0.60, 1.34) days). CONCLUSIONS: There is no evidence that the routine use of IPM improves perioperative and post-operative outcomes compared to no Pringle manoeuvre and its routine may not be recommended.