A “concept” refers to what exists in the mind as a representation (as in something comprehended) or as a formulation (as in a plan). It is generally understood as “any idea of what a thing ought to ...be” (Merriam-Webster). From that premise, an “idea” cannot be compartmentalized or rigidly defined as exclusively belonging to any single individual or school of thought. The utility of a concept is inherently linked to its adaptability to the needs and conditions of the time. I state this upfront because over the past several decades, the concept of the epileptogenic zone (EZ) has become so crucial to the foundation of major schools of surgical epilepsy that discussions and opinions on the topic have essentially sought to legitimize one view while criticizing the other. This review is not a referendum on any specific definition of the EZ but rather a chronological analysis of the historical evolution of this concept and the invasive EEG tools used to study it. The goal is to highlight common ground necessary to tackle the ever-present challenge of defining the ideal resection for a patient with drug-resistant focal epilepsy.
Brain surgery offers the best chance of seizure-freedom for patients with focal drug-resistant epilepsy, but only 50% achieve sustained seizure-freedom. With the explosion of data collected during ...routine presurgical evaluations and recent advances in computational science, we now have a tremendous potential to achieve precision epilepsy surgery: a data-driven tailoring of surgical planning. This review highlights the clinical need, the relevant computational science focusing on machine learning, and discusses some specific applications in epilepsy surgery.
Three neuromodulation therapies have been appropriately tested and approved in refractory focal epilepsies: vagus nerve stimulation (VNS), deep brain stimulation of the anterior nucleus of the ...thalamus (ANT-DBS), and closed-loop responsive neurostimulation of the epileptogenic zone or zones. These therapies are primarily palliative. Only a few individuals have achieved complete freedom from seizures for more than 12 months with these therapies, whereas more than half have benefited from long-term reduction in seizure frequency of more than 50%. Implantation-related adverse events primarily include infection and pain at the implant site. Intracranial haemorrhage is a frequent adverse event for ANT-DBS and responsive neurostimulation. Other stimulation-specific side-effects are observed with VNS and ANT-DBS. Biomarkers to predict response to neuromodulation therapies are not available, and high-level evidence to aid decision making about when and for whom these therapies should be preferred over other antiepileptic treatments is scant. Future studies are thus needed to address these shortfalls in knowledge, approve other forms of neuromodulation, and develop personalised closed-loop therapies with embedded machine learning. Until then, neuromodulation could be considered for individuals with intractable seizures, ideally after the possibility of curative surgical treatment has been carefully assessed and ruled out or judged less appropriate.
ESI is a noninvasive technique that uses mathematical algorithms to localize the source of a given EEG pattern in real time, 2 while DFC refers to methods that appeal to temporal precedence of ...electrophysiology or imaging data to construct macroscopic neural networks and infer directed connectivity. 3 The classical study subject matter for both ESI and DFC has been high‐density EEG or iEEG. The authors selected 20 patients with temporal lobe epilepsy (TLE) and 14 with extratemporal lobe epilepsy (ETLE) who had a focal magnetic resonance imaging lesion, invasively well‐characterized presumed EZ, and ≥10 interictal epileptic discharges of the same (single) type on low‐density EEG. ...the true significance of higher concordance in TLE vs ETLE cannot be judged given the fact that TLE resections were larger than those in ETLE, which by itself increases the likelihood of including an area of abnormal ESI measurements in the resection.
Three neuromodulation therapies, all using implanted device and electrodes, have been approved to treat adults with drug-resistant focal epilepsy, namely, the vagus nerve stimulation in 1995, deep ...brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) in 2018 (2010 in Europe), and responsive neurostimulation (RNS) in 2014. Indications for VNS have more recently extended to children down to age of 4. Limited or anecdotal data are available in other epilepsy syndromes and refractory/super-refractory status epilepticus. Overall, neuromodulation therapies are palliative, with only a minority of patients achieving long-term seizure freedom, justifying favoring such treatments in patients who are not good candidates for curative epilepsy surgery. About half of patients implanted with VNS, ANT-DBS, and RNS have 50% or greater reduction in seizures, with long-term data suggesting increased efficacy over time. Besides their impact on seizure frequency, neuromodulation therapies are associated with various benefits and drawbacks in comparison to antiseizure drugs. Yet, we lack high-level evidence to best position each neuromodulation therapy in the treatment pathways of persons with difficult-to-treat epilepsy.
Coronavirus Disease 2019 is a pandemic that is straining healthcare resources, mainly hospital beds. Multiple risk factors of disease progression requiring hospitalization have been identified, but ...medical decision-making remains complex.
To characterize a large cohort of patients hospitalized with COVID-19, their outcomes, develop and validate a statistical model that allows individualized prediction of future hospitalization risk for a patient newly diagnosed with COVID-19.
Retrospective cohort study of patients with COVID-19 applying a least absolute shrinkage and selection operator (LASSO) logistic regression algorithm to retain the most predictive features for hospitalization risk, followed by validation in a temporally distinct patient cohort. The final model was displayed as a nomogram and programmed into an online risk calculator.
One healthcare system in Ohio and Florida.
All patients infected with SARS-CoV-2 between March 8, 2020 and June 5, 2020. Those tested before May 1 were included in the development cohort, while those tested May 1 and later comprised the validation cohort.
Demographic, clinical, social influencers of health, exposure risk, medical co-morbidities, vaccination history, presenting symptoms, medications, and laboratory values were collected on all patients, and considered in our model development.
4,536 patients tested positive for SARS-CoV-2 during the study period. Of those, 958 (21.1%) required hospitalization. By day 3 of hospitalization, 24% of patients were transferred to the intensive care unit, and around half of the remaining patients were discharged home. Ten patients died. Hospitalization risk was increased with older age, black race, male sex, former smoking history, diabetes, hypertension, chronic lung disease, poor socioeconomic status, shortness of breath, diarrhea, and certain medications (NSAIDs, immunosuppressive treatment). Hospitalization risk was reduced with prior flu vaccination. Model discrimination was excellent with an area under the curve of 0.900 (95% confidence interval of 0.886-0.914) in the development cohort, and 0.813 (0.786, 0.839) in the validation cohort. The scaled Brier score was 42.6% (95% CI 37.8%, 47.4%) in the development cohort and 25.6% (19.9%, 31.3%) in the validation cohort. Calibration was very good. The online risk calculator is freely available and found at https://riskcalc.org/COVID19Hospitalization/.
Retrospective cohort design.
Our study crystallizes published risk factors of COVID-19 progression, but also provides new data on the role of social influencers of health, race, and influenza vaccination. In a context of a pandemic and limited healthcare resources, individualized outcome prediction through this nomogram or online risk calculator can facilitate complex medical decision-making.
The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to unprecedented social and economic consequences. The risk of ...morbidity and mortality due to COVID-19 increases dramatically in the presence of coexisting medical conditions, while the underlying mechanisms remain unclear. Furthermore, there are no approved therapies for COVID-19. This study aims to identify SARS-CoV-2 pathogenesis, disease manifestations, and COVID-19 therapies using network medicine methodologies along with clinical and multi-omics observations. We incorporate SARS-CoV-2 virus-host protein-protein interactions, transcriptomics, and proteomics into the human interactome. Network proximity measurement revealed underlying pathogenesis for broad COVID-19-associated disease manifestations. Analyses of single-cell RNA sequencing data show that co-expression of ACE2 and TMPRSS2 is elevated in absorptive enterocytes from the inflamed ileal tissues of Crohn disease patients compared to uninflamed tissues, revealing shared pathobiology between COVID-19 and inflammatory bowel disease. Integrative analyses of metabolomics and transcriptomics (bulk and single-cell) data from asthma patients indicate that COVID-19 shares an intermediate inflammatory molecular profile with asthma (including IRAK3 and ADRB2). To prioritize potential treatments, we combined network-based prediction and a propensity score (PS) matching observational study of 26,779 individuals from a COVID-19 registry. We identified that melatonin usage (odds ratio OR = 0.72, 95% CI 0.56-0.91) is significantly associated with a 28% reduced likelihood of a positive laboratory test result for SARS-CoV-2 confirmed by reverse transcription-polymerase chain reaction assay. Using a PS matching user active comparator design, we determined that melatonin usage was associated with a reduced likelihood of SARS-CoV-2 positive test result compared to use of angiotensin II receptor blockers (OR = 0.70, 95% CI 0.54-0.92) or angiotensin-converting enzyme inhibitors (OR = 0.69, 95% CI 0.52-0.90). Importantly, melatonin usage (OR = 0.48, 95% CI 0.31-0.75) is associated with a 52% reduced likelihood of a positive laboratory test result for SARS-CoV-2 in African Americans after adjusting for age, sex, race, smoking history, and various disease comorbidities using PS matching. In summary, this study presents an integrative network medicine platform for predicting disease manifestations associated with COVID-19 and identifying melatonin for potential prevention and treatment of COVID-19.
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