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ObjectiveTo evaluate association between biomarkers and outcomes in COVID-19 hospitalised patients. COVID-19 pandemic has been a challenge. Biomarkers have always played an important role in clinical decision making in various infectious diseases. It is crucial to assess the role of biomarkers in evaluating severity of disease and appropriate allocation of resources.Design and settingSystematic review and meta-analysis. English full text observational studies describing the laboratory findings and outcomes of COVID-19 hospitalised patients were identified searching PubMed, Web of Science, Scopus, medRxiv using Medical Subject Headings (MeSH) terms COVID-19 OR coronavirus OR SARS-CoV-2 OR 2019-nCoV from 1 December 2019 to 15 August 2020 following Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines.ParticipantsStudies having biomarkers, including lymphocyte, platelets, D-dimer, lactate dehydrogenase (LDH), C reactive protein (CRP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, procalcitonin (PCT) and creatine kinase (CK), and describing outcomes were selected with the consensus of three independent reviewers.Main outcome measuresComposite poor outcomes include intensive care unit admission, oxygen saturation <90%, invasive mechanical ventilation utilisation, severe disease, in-hospital admission and mortality. The OR and 95% CI were obtained and forest plots were created using random-effects models. Publication bias and heterogeneity were assessed by sensitivity analysis.Results32 studies with 10 491 confirmed COVID-19 patients were included. We found that lymphopenia (pooled-OR: 3.33 (95% CI: 2.51–4.41); p<0.00001), thrombocytopenia (2.36 (1.64–3.40); p<0.00001), elevated D-dimer (3.39 (2.66–4.33); p<0.00001), elevated CRP (4.37 (3.37–5.68); p<0.00001), elevated PCT (6.33 (4.24–9.45); p<0.00001), elevated CK (2.42 (1.35–4.32); p=0.003), elevated AST (2.75 (2.30–3.29); p<0.00001), elevated ALT (1.71 (1.32–2.20); p<0.00001), elevated creatinine (2.84 (1.80–4.46); p<0.00001) and LDH (5.48 (3.89–7.71); p<0.00001) were independently associated with higher risk of poor outcomes.ConclusionOur study found a significant association between lymphopenia, thrombocytopenia and elevated levels of CRP, PCT, LDH, D-dimer and COVID-19 severity. The results have the potential to be used as an early biomarker to improve the management of COVID-19 patients, by identification of high-risk patients and appropriate allocation of healthcare resources in the pandemic.

BackgroundArtificial intelligence (AI) has influenced all aspects of human life and neurology is no exception to this growing trend. The aim of this paper is to guide medical practitioners on the relevant aspects of artificial intelligence, i.e., machine learning, and deep learning, to review the development of technological advancement equipped with AI, and to elucidate how machine learning can revolutionize the management of neurological diseases. This review focuses on unsupervised aspects of machine learning, and how these aspects could be applied to precision neurology to improve patient outcomes. We have mentioned various forms of available AI, prior research, outcomes, benefits and limitations of AI, effective accessibility and future of AI, keeping the current burden of neurological disorders in mind.DiscussionThe smart device system to monitor tremors and to recognize its phenotypes for better outcomes of deep brain stimulation, applications evaluating fine motor functions, AI integrated electroencephalogram learning to diagnose epilepsy and psychological non-epileptic seizure, predict outcome of seizure surgeries, recognize patterns of autonomic instability to prevent sudden unexpected death in epilepsy (SUDEP), identify the pattern of complex algorithm in neuroimaging classifying cognitive impairment, differentiating and classifying concussion phenotypes, smartwatches monitoring atrial fibrillation to prevent strokes, and prediction of prognosis in dementia are unique examples of experimental utilizations of AI in the field of neurology. Though there are obvious limitations of AI, the general consensus among several nationwide studies is that this new technology has the ability to improve the prognosis of neurological disorders and as a result should become a staple in the medical community.ConclusionAI not only helps to analyze medical data in disease prevention, diagnosis, patient monitoring, and development of new protocols, but can also assist clinicians in dealing with voluminous data in a more accurate and efficient manner.

Stroke is the fifth leading cause of death in the United States with a huge burden on health care. Acute ischemic stroke (AIS) accounts for 87% of all stroke. The use of thrombolytic agents in AIS treatment is well known since 1950 but no FDA approval until 1996, due to lack of strong evidence showing benefits outweigh the risk of intracranial hemorrhage. The NINDS trial led to the approval of intravenous tissue plasminogen activator treatment (IV recombinant tPA) within 3 h of stroke. Due to this limitation of 3–4.5 h. window, evolution began in the development of effective endovascular therapy (EVT). Multiple trials were unsuccessful in establishing the strong evidence for effectiveness of EVT. In 2015, MR CLEAN trial made progress and showed improved outcomes with EVT in AIS patients with large vessel occlusion (LVO), with 6-h window period. In 2018, two major trials—DAWN and DEFUSE 3—along with few other trials had shown improved outcomes with EVT and stretched window period from 6 to 24 h. AHA Stroke Council is constantly working to provide focused guidelines and recommendations in AIS management since 2013. SVIN had started the initiative “Mission Thrombectomy-2020” to increase global EVT utilization rate 202,000 procedures by 2020. Physicians are using safer and easier approach like brachial and radial approach for EVT. TeleNeurology and artificial intelligence also played a significant role in increasing the availability of IV recombinant tPA in AIS treatment in remote hospitals and also in screening, triaging and identifying LVO patients for EVT. In this review article, we aim to describe the history of stroke management along with the new technological advancements in AIS treatment.

BackgroundDue to pro-inflammatory and hypercoagulation states, COVID-19 infection is believed to increase the risk of stroke and worsen the outcomes of the patients having pre-existing cerebrovascular diseases (CeVD). There is limited literature on prevalence of pre-existing CeVD in COVID-19 patients, and outcomes are unknown. The objective of this meta-analysis is to evaluate the outcomes of COVID-19 patients with pre-existing CeVD.MethodsEnglish full-text-observational studies having data on epidemiological characteristics of COVID-19 patients were identified searching PubMed, Web of Science, and Scopus using MeSH-terms COVID-19 OR coronavirus OR SARS-CoV-2 OR 2019-nCoV from December 1, 2019 to April 30, 2020. Studies having CeVD or stroke as one of the pre-existing comorbidities and described outcomes including intensive care unit (ICU) admission, mechanical ventilation utilization, and mortality were selected with consensus of three reviewers. Following MOOSE protocol, 11 studies were included. The pooled prevalence of CeVD and outcomes were calculated. Meta-regression was performed, and correlation coefficient (r) and odds ratio (OR) were estimated to evaluate the effects of pre-existing CeVD on outcomes of COVID-19 patients. Meta-analysis with random-effects model was used to calculate OR along with its 95% CI from the studies containing data on composite poor outcome.ResultsOut of 8/11 studies showing data on mortality and mechanical ventilation, and 7/11 on ICU admission, pooled prevalence of pre-existing CeVD was 4.4% (244/4987). In age-adjusted meta-regression analysis, pre-existing CeVD was associated with ICU admission [r: 0.60; OR: 1.82 (1.25–2.69)], mechanical ventilation [r: 0.29; OR: 1.33 (1.09–1.63)], and mortality [r: 0.35; OR: 1.42 (1.14–1.77)] amongst COVID-19 hospitalizations. 9/11 studies reported data on binary composite outcomes, the pooled prevalence of pre-existing CeVD was 4.3% (155/3603) and 7.46% (83/1113) amongst COVID-19 hospitalizations and COVID-19 hospitalization-related poor outcomes, respectively. In meta-analysis, COVID-19 patient with pre-existing CeVD had 2.67-fold (1.75–4.06) higher odds of poor outcomes.ConclusionCOVID-19 patients with pre-existing cerebrovascular disease have poor outcomes and extra precautions should be taken in managing such patients during the ongoing pandemic.

THP-1 cells differentiated with phorbol 12-myristate 13-acetate (PMA) are widely used as a model for function and biology of human macrophages. However, the conditions used for differentiation, particularly the concentration of PMA and the duration of treatment, vary widely. Here we compare several differentiation conditions and compare the ability of THP-1 macrophages to interact with the facultative intracellular pathogen Salmonella enterica serovar Typhimurium. The results show that THP-1 macrophages differentiated in high concentrations of PMA rapidly died following infection whereas those differentiated in low concentrations of PMA survived and were able to control the intracellular bacteria similar to primary human macrophages.

We aimed to identify prevalence and association of comorbid chronic kidney disease (CKD), acute kidney injury (AKI) and utilization prevalence of continuous renal replacement therapy (CRRT) in COVID-19-hospitalized patients as a function of severity status. With the ongoing struggle across the globe to combat COVID-19 disease, published literature has described the role of kidney disease in COVID-19 patients based on single/multicenter experiences across the globe. We extracted data from observational studies describing comorbid CKD, AKI and CRRT and outcomes and severity of COVID-19-hospitalized patients from December 1, 2019–August 20, 2020 following PRISMA guidelines. Severity of COVID-19 includes intensive care unit admission, oxygen saturation < 90%, invasive mechanical ventilation utilization, in-hospital admission and mortality. Meta-analysis was performed using a random-effects model to calculate pooled estimates, and forest plots were created. In total, 29 studies with 15,017 confirmed COVID-19 patients were included. The overall prevalence of AKI was 11.6% [(430/3693)], comorbid CKD 9.7% [(1342/13,728)] and CRRT 2.58% [(102/3946)] in our meta-analysis. We also found higher odds of comorbid CKD (pooled OR: 1.70; 95%CI: 1.21–2.40; p = 0.002), AKI (8.28; 4.42–15.52; p < 0.00001) and utilization of CRRT (16.90; 9.00–31.74; p < 0.00001) in patients with severe COVID-19 disease. Conclusion Our meta-analysis suggests that comorbid CKD, AKI and utilization of CRRT were significantly associated with COVID-19 disease severity. Clinicians should focus on early triaging of COVID-19 patients with comorbid CKD and at risk for AKI to prevent complication and mortality.

Coronavirus disease-2019 (COVID-19), a pandemic that brought the whole world to a standstill, has led to financial and health care burden. We aimed to evaluate epidemiological characteristics, needs of resources, outcomes, and global burden of the disease. Systematic review was performed searching PubMed from December 1, 2019, to March 25, 2020, for full-text observational studies that described epidemiological characteristics, following MOOSE protocol. Global data were collected from the JHU-Corona Virus Resource Center, WHO-COVID-2019 situation reports, KFF.org, and Worldometers.info until March 31, 2020. The prevalence percentages were calculated. The global data were plotted in excel to calculate case fatality rate (CFR), predicted CFR, COVID-19 specific mortality rate, and doubling time for cases and deaths. CFR was predicted using Pearson correlation, regression models, and coefficient of determination. From 21 studies of 2747 patients, 8.4% of patients died, 20.4% recovered, 15.4% were admitted to ICU and 14.9% required ventilation. COVID-19 was more prevalent in patients with hypertension (19.3%), smoking (11.3%), diabetes mellitus (10%), and cardiovascular diseases (7.4%). Common complications were pneumonia (82%), cardiac complications (26.4%), acute respiratory distress syndrome (15.7%), secondary infection (11.2%), and septic shock (4.3%). Though CFR and COVID-19 specific death rates are dynamic, they were consistently high for Italy, Spain, and Iran. Polynomial growth models were best fit for all countries for predicting CFR. Though many interventions have been implemented, stern measures like nationwide lockdown and school closure occurred after very high infection rates (>10cases per 100 000population) prevailed. Given the trend of government measures and decline of new cases in China and South Korea, most countries will reach the peak between April 1-20, if interventions are followed. A collective approach undertaken by a responsible government, wise strategy implementation and a receptive population may help contain the spread of COVID-19 outbreak. Close monitoring of predictive models of such indicators in the highly affected countries would help to evaluate the potential fatality if the second wave of pandemic occurs. The future studies should be focused on identifying accurate indicators to mitigate the effect of underestimation or overestimation of COVID-19 burden.

Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy (SMEI), is one of the rare early childhood intractable epileptic encephalopathies associated with pleomorphic seizure activity, cognitive decline, motor, and behavioral abnormalities. The convulsive seizure is the most common type seen in DS. After the first episode of seizure-like activity, behavioral disorders and cognitive decline are progressive and long-lasting. The most common etiology identified in patients with DS is a de-novo genetic mutation alpha-1 subunit of voltage-gated calcium channel gene (SCN1A). DS is diagnosed clinically and if unclear, genetic testing is recommended. DS treatment options include anti-epileptic drugs and cannabinoids; ketogenic diet therapy and surgical options such as the deep brain and vagal nerve stimulation. Due to drug-refractory epilepsy in DS, many more therapies are being investigated to increase the longevity of patients.

In rural and underserved areas, there are restrictions in healthcare due to the lack of availability of neurologists; patients have to travel long distances to receive the required care. Considering the fact that neurological conditions have large mortality and disability rates, there is a need for innovative services like tele-neurology. It is an important tool in improving the health and quality of life by using different ways of communication between neurologists and patients, or neurologists and other providers. We examine the current types of facilities available in tele-neurology, as well as outcomes, barriers, limitations, legal litigations, and the multidisciplinary nature based on prior studies. We have also suggested recommendations for the future of tele-neurology including effective-accessibility and inexpensive-utilization in developing countries. There are various tele-health programs created by The Veterans Health Administration including a clinical video tele-health (CVT) system. This system allows direct patient care of veterans by neurologists. The University of South Carolina implemented a web-based tele-stroke program in which acute ischemic stroke patients were treated in the Emergency Department (ED) of rural hospitals by neurologists, after consulting with rural ED physicians. With growing technology and popularity of tele-neurology, there are now international collaborative efforts in tele-medicine that are looking to be adapted to tele-neurology. Thus, tele-neurology can provide quality neurological care with patient satisfaction, as well as time and cost savings. The tele-stroke group established by TRUST-tPA trial (Therapeutic Trial Evaluating Efficacy of Telemedicine (TELESTROKE) of Patients With Acute Stroke) has 10 community hospital-emergency rooms that were connected to a stroke center. It was found that tele-stroke is appropriate in places where there is no way for a patient to access a stroke unit within a 4.5-hour time window. Like other tele-neurology subtypes, tele-epilepsy and pediatric tele-neurology also offer more follow-up care to people of remote areas which have limited access. There are other subtypes like mental health, chronic neurological care, and hospitalist which are very effective in improving outcome and quality of life of people living in remote areas. Tele-neurology has effectively reduced travel costs and times; there is high patient satisfaction and reduced disparity for general and specialized neurological care. But there are certain limitations like large equipment costs, certain bandwidth requirement, and trained staff to use the equipment. Transmission of patient information using public internet raises the concern of legality. There should be sufficient encryption to satisfy the Health Insurance Portability and Accountability Act (HIPAA) requirements to ensure patient confidentiality and safety of personal data. The adaptation of tele-neurology is a powerful and innovative way to enhance healthcare in areas with a shortage of specialists. Implementation of this tool is limited due to cost burden, lack of expertise to implement necessary technology, legal litigations, and suitable financial and professional incentives for the users. This review focuses on the trajectory of utilization and the issues to be addressed in order to provide the full benefits of tele-neurology to undeserved communities in the future.