Autoimmune Epilepsy: The Evolving Science of Neural Autoimmunity and Its Impact on Epilepsy Management

2018 ◽  
Vol 38 (03) ◽  
pp. 290-302 ◽  
Author(s):  
Orna O'Toole ◽  
Amy Quek
Keyword(s):  
Patient Outcomes ◽  
Treatment Options ◽  
Immunosuppressive Treatment ◽  
Substantial Reduction ◽  
Risk Scores ◽  
Seizure Freedom ◽  
Clinical Approach ◽  
Treatment Trial ◽  
Autoimmune Epilepsy ◽  
Immune Mediated

AbstractAutoimmune epilepsy is increasingly recognized as a distinct clinical entity, driven in large part by the recent discovery of neural autoantibodies in patients with isolated or predominant epilepsy presentations. Detection of neural autoantibodies in high-risk epilepsy patients supports an immune-mediated cause of seizures and, if applicable, directs the search for an underlying cancer when the paraneoplastic association of the associated antibody is compelling. Early diagnosis of autoimmune epilepsy is crucial, as prompt initiation of immunosuppressive treatment increases the likelihood of achieving either seizure freedom or a substantial reduction in seizure frequency. A practical clinical approach that incorporates risk scores to guide patient selection on the basis of clinical features, neural autoantibodies, and a treatment trial of immunotherapy is suggested. Elucidating an immunological basis of epilepsy provides neurologists with wider treatment options (incorporating immune-suppressive treatment), in addition to standard antiepileptic drugs, which often improves patient outcomes.

Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Toward an Individualized Approach

Nephron ◽  
2021 ◽  
pp. 1-17
Author(s):  
Javier Villacorta ◽  
Laura Martinez-Valenzuela ◽  
Irene Martin-Capon ◽  
Juliana Bordignon-Draibe
Keyword(s):  
Alternative Pathway ◽  
Treatment Options ◽  
Immunosuppressive Treatment ◽  
Standard Of Care ◽  
Antineutrophil Cytoplasmic Antibody ◽  
Organ Damage ◽  
Cumulative Exposure ◽  
Clinical Approach ◽  
Clinical Syndromes ◽  
Individualized Approach

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), characterized by the presence of autoantibodies to neutrophil cytoplasmic antigens, proteinase 3 (PR3), and myeloperoxidase (MPO), typically involves small blood vessels of the respiratory tract and kidneys. It includes distinct clinical syndromes: microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic GPA. GPA is commonly associated with PR3-ANCA, while MPA is associated with MPO-ANCA. AAVs have a complex pathogenesis, influenced by genetics and environmental factors. There is evidence for a loss of tolerance to neutrophil proteins, which leads to ANCA-mediated neutrophil activation and injury, with effector T cells and activation of the alternative pathway of the complement also involved. Advances in immunosuppressive treatment have drastically reduced mortality of AAV in the past decades, opting for a more individualized approach. Careful assessment of ANCA specificity, disease activity, organ damage, and quality of life allows for a tailored immunosuppressive therapy. Contemporary AAV treatment is characterized by regimens that minimize the cumulative exposure to glucocorticoids and cyclophosphamide, and novel approaches including complement blockage and immunosuppressant combinations might be the standard of care in the future. In this review, we examine the pathogenesis, clinical approach, and evidence-based treatment options for the management of AAV patients.

scholarly journals A metabolomic endotype of bioenergetic dysfunction predicts mortality in critically ill patients with acute respiratory failure

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Raymond J. Langley ◽  
Marie E. Migaud ◽  
Lori Flores ◽  
J. Will Thompson ◽  
Elizabeth A. Kean ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Acute Respiratory Failure ◽  
Patient Outcomes ◽  
Medical Intensive Care Unit ◽  
Close Association ◽  
Treatment Options ◽  
Feature Model ◽  
High Morbidity ◽  
Medical Intensive Care ◽  
Poor Outcomes

AbstractAcute respiratory failure (ARF) requiring mechanical ventilation, a complicating factor in sepsis and other disorders, is associated with high morbidity and mortality. Despite its severity and prevalence, treatment options are limited. In light of accumulating evidence that mitochondrial abnormalities are common in ARF, here we applied broad spectrum quantitative and semiquantitative metabolomic analyses of serum from ARF patients to detect bioenergetic dysfunction and determine its association with survival. Plasma samples from surviving and non-surviving patients (N = 15/group) were taken at day 1 and day 3 after admission to the medical intensive care unit and, in survivors, at hospital discharge. Significant differences between survivors and non-survivors (ANOVA, 5% FDR) include bioenergetically relevant intermediates of redox cofactors nicotinamide adenine dinucleotide (NAD) and NAD phosphate (NADP), increased acyl-carnitines, bile acids, and decreased acyl-glycerophosphocholines. Many metabolites associated with poor outcomes are substrates of NAD(P)-dependent enzymatic processes, while alterations in NAD cofactors rely on bioavailability of dietary B-vitamins thiamine, riboflavin and pyridoxine. Changes in the efficiency of the nicotinamide-derived cofactors’ biosynthetic pathways also associate with alterations in glutathione-dependent drug metabolism characterized by substantial differences observed in the acetaminophen metabolome. Based on these findings, a four-feature model developed with semi-quantitative and quantitative metabolomic results predicted patient outcomes with high accuracy (AUROC = 0.91). Collectively, this metabolomic endotype points to a close association between mitochondrial and bioenergetic dysfunction and mortality in human ARF, thus pointing to new pharmacologic targets to reduce mortality in this condition.

scholarly journals Identification of 38 novel loci for systemic lupus erythematosus and genetic heterogeneity between ancestral groups

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yong-Fei Wang ◽  
Yan Zhang ◽  
Zhiming Lin ◽  
Huoru Zhang ◽  
Ting-You Wang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Genome Wide Association Study ◽  
Age Of Onset ◽  
Treatment Options ◽  
Human Leukocyte ◽  
Risk Scores ◽  
Systemic Lupus ◽  
Disease Manifestation ◽  
A Genome

AbstractSystemic lupus erythematosus (SLE), a worldwide autoimmune disease with high heritability, shows differences in prevalence, severity and age of onset among different ancestral groups. Previous genetic studies have focused more on European populations, which appear to be the least affected. Consequently, the genetic variations that underlie the commonalities, differences and treatment options in SLE among ancestral groups have not been well elucidated. To address this, we undertake a genome-wide association study, increasing the sample size of Chinese populations to the level of existing European studies. Thirty-eight novel SLE-associated loci and incomplete sharing of genetic architecture are identified. In addition to the human leukocyte antigen (HLA) region, nine disease loci show clear ancestral differences and implicate antibody production as a potential mechanism for differences in disease manifestation. Polygenic risk scores perform significantly better when trained on ancestry-matched data sets. These analyses help to reveal the genetic basis for disparities in SLE among ancestral groups.

scholarly journals POS1180 TREATMENT COMPLIANCE OF PATIENTS WITH RHEUMATOID ARTHRITIS DURING THE FIRST WAVE OF THE SARS-CoV-2/COVID-19 PANDEMIC IN PORTUGAL: RESULTS FROM THE COVID IN RA (COVIDRA) SURVEY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 871.2-871
Author(s):  
F. Araujo ◽  
N. Gonçalves ◽  
A. F. Mourão
Keyword(s):  
Rheumatoid Arthritis ◽  
Inflammatory Diseases ◽  
Immunosuppressive Treatment ◽  
Treatment Compliance ◽  
Web Based ◽  
Symptoms Of Depression ◽  
Immune Mediated ◽  
Attending Physician ◽  
The Impact ◽  
E Mail

Background:The outcomes of the infection by the SARS-CoV-2 in patients with immune-mediated inflammatory diseases were largely unknown during the early days of the COVID-19 pandemic. It was hypothesized that these patients were at higher risk of morbidity and mortality due to their inherent immune dysfunction and immunosuppressive therapy. Several rheumatology societies issued recommendations urging patients not to stop their anti-rheumatic treatments.Objectives:To assess treatment compliance of patients with rheumatoid arthritis (RA) during the first wave of the SARS-CoV-2/COVID-19 pandemic in Portugal.Methods:The web-based survey COVIDRA (COVID in RA) was developed to assess the impact of the first wave mandatory confinement in patients with RA focusing on 5 domains: RA symptoms, attitudes towards medication, employment status, physical exercise and mental health. The questionnaire was sent to RA patients through e-mail and social media of the Portuguese Society of Rheumatology and two patient associations; and it was filled locally at two rheumatology centers in Lisbon. Recruitment took place during June and July 2020. Descriptive statistics were generated by the survey software and were afterwards transported and evaluated using appropriate biostatistics software.Results:We obtained 441 valid questionnaires. Most respondents were female (88.4%), caucasian (93.6%), with a mean age of 58 (+/-13) years. The majority (57.6%) had longstanding disease (>10 years) and were treated with csDMARDs (63.2%) and/or bDMARDs/tsDMARDS (23,7%). Only 14% (N=61) discontinued or reduced the dosage or frequency of their RA treatment. Most of these changes were previously planned by the attending physician (27.9%). Only 11 patients (18%) discontinued their immunosuppressive medication out of fear of becoming infected with SARS-CoV-2 (corresponding to 2.5% of total responders). Another 11 patients did so because they had no prescription, couldn’t go to the community/hospital pharmacy or couldn’t afford the medication. Although these numbers preclude any statistical analysis, when compared to patients who persisted on their treatment, those discontinuing due to fear of contagion were younger (56.4 vs 58.5 years), all female (100 vs 86.8%), with long-lasting disease (≥ 11 years) (90.9% vs 57.5%), more frequently treated with bDMARDs (36.4 vs 23.1%) and presenting more symptoms of depression (54.5 vs 49.7%).Conclusion:Most RA patients complied with their treatment during the first wave of the SARS-CoV-2 pandemic in Portugal. Only a minority changed their immunosuppressive treatment due to fear of SARS-CoV-2 infection. Very similar rates of immunosuppressive discontinuation due to fear of contagion were reported by other authors (such as Schmeiser et al, Pineda-sic et al and Fragoulis et al).Disclosure of Interests:Filipe Araujo Speakers bureau: Pfizer, Biogen, Novartis, Menarini, Consultant of: MSD, Nuno Gonçalves: None declared, Ana Filipa Mourão: None declared.

scholarly journals 1186. Cefazolin inoculum effect predicts reduced susceptibility to other antibiotics and patient outcomes in MSSA endovascular infections

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S617-S617
Author(s):  
Dan Smelter ◽  
Sue McCrone ◽  
Warren Rose
Keyword(s):  
Infective Endocarditis ◽  
Mortality Rate ◽  
Patient Outcomes ◽  
Treatment Options ◽  
Fold Increase ◽  
Specific Mechanism ◽  
Research Support ◽  
High Burden ◽  
Low Toxicity ◽  
Inoculum Effect

Abstract Background MSSA Infective endocarditis (IE) is inherently a high-burden infection with up to a 30% mortality rate. Cefazolin is an appealing treatment option for IE with low toxicity and a favorable dosing scheme. However, cefazolin has been associated with treatment failure in IE, attributed to an inoculum effect. The specific mechanism underlying the cefazolin inoculum effect (CIE) remains undetermined, but CIE has been linked to both blaZ expression and agr dysfunction. This study aims to determine whether CIE is linked to reduced susceptibility to other antibiotics and worse outcomes regardless of therapy in MSSA endovascular infections. Methods Sixty-four MSSA strains were collected from patients with endovascular infections not treated with cefazolin. To determine CIE phenotype, strains were cultured and MICs assayed for cefazolin, nafcillin, and vancomycin at 107 CFU/mL for high-inocula (HI) and 105 CFU/mL for standard-inocula (SI). This study defined CIE as a ≥ 4-fold increase in MIC at HI compared to SI, with at least an MIC of 4 mg/L at HI. Nitrocefin disks identified blaZ expression, and beta lysin disks were used to determine hemolysin type and agr function. Patient outcomes of mortality and bacteremia duration were assessed across cohorts. Results Twenty-four strains exhibit a CIE (38%), with 10 strains having an MIC of ≥ 32mg/L at HI. Nafcillin and vancomycin also had an inoculum effect, uncoupled from the CIE and occurring at a lower frequency and amplitude at HI. Presence of CIE had a greater association with blaZ expression (71% vs 25%) than agr dysfunction (38% vs 20%). 50% (9/18) of CIE infections were cleared within 48 hours while 77% (20/26) of CIE-negative infections were cleared within 48 hours (P=0.106). However, presence of CIE was not associated with increased mortality (25% CIE-positive vs 35%; P=0.578) Conclusion Previous studies for CIE failed to enrich for isolates from endovascular sources, where inocula are known to be high. This study presents one of the largest endovascular source cohorts for CIE evaluation. It identifies that CIE prevalence (38%) is higher than reports from diverse infection sources (10-36%). CIE appears to predict bacteremia duration with other MSSA treatment options, suggesting mechanisms independent of blaZ and agr function for this phenomenon. Disclosures Warren Rose, PharmD, MPH, Merck (Grant/Research Support)Paratek (Grant/Research Support)

scholarly journals History of the Military Nurse Corps and the 1918 Influenza Pandemic: Lessons for the 2019 Coronavirus Pandemic

2020 ◽  
Author(s):  
Laura A Talbot ◽  
E Jeffrey Metter ◽  
Heather King
Keyword(s):  
World War I ◽  
Patient Outcomes ◽  
Influenza Pandemic ◽  
Treatment Options ◽  
Primary Therapy ◽  
World War ◽  
Military Nursing ◽  
History Of ◽  
1918 Influenza ◽  
The Military

ABSTRACT During World War I, the 1918 influenza pandemic struck the fatigued combat troops serving on the Western Front. Medical treatment options were limited; thus, skilled military nursing care was the primary therapy and the best indicator of patient outcomes. This article examines the military nursing’s role in the care of the soldiers during the 1918 flu pandemic and compares this to the 2019 coronavirus pandemic.

Treatment of Heparin-Induced Thrombocytopenia

2002 ◽  
Vol 36 (3) ◽  
pp. 489-503 ◽  
Author(s):  
William E Dager ◽  
Richard H White
Keyword(s):  
Adverse Reaction ◽  
Treatment Options ◽  
Clinical Manifestations ◽  
Low Molecular Weight ◽  
National Library ◽  
Severe Adverse Reaction ◽  
Heparin Induced Thrombocytopenia ◽  
Immune Mediated ◽  
Study Selection ◽  
Clinical Conditions

OBJECTIVE: To describe heparin-induced thrombocytopenia (HIT or HIT-2), an immune-mediated adverse reaction to heparin or low-molecular-weight heparin. Available treatment options and considerations in developing a therapy approach are discussed. DATA SOURCES: A search of the National Library of Medicine (1992–June 2001) was done to identify pertinent literature. Additional references were reviewed from selected articles. STUDY SELECTION: Articles related to laboratory recognition and treatment options of HIT, including the use of agents in selected clinical conditions, were reviewed and included. CONCLUSIONS: HIT is a rare but potentially severe adverse reaction to heparin that was, until recently, poorly understood and had limited treatment options. Recent advances describing the recognition and clinical manifestations of immune-mediated HIT, including recently available antithrombotic treatment options, have dramatically changed outcomes for patients having this syndrome.

Abstract TP252: Using Hospital Door-to-Needle Times to Individualize Hospital Bypass Times in Order to Minimize Regional Onset-to-Needle Times

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Jin-Moo Lee ◽  
Andria Ford ◽  
Jo-Ann Burns ◽  
Peter Panagos
Keyword(s):  
Patient Outcomes ◽  
Treatment Options ◽  
Stroke Care ◽  
Smartphone Application ◽  
System Level ◽  
Acute Stroke Care ◽  
Web Based ◽  
Arrival Times ◽  
Get With The Guidelines ◽  
Individual Hospital

Introduction: With enhanced treatment options but limited resources, acute stroke care is becoming regionalized. Regional pre-hospital triage plans are being developed to permit bypass of certain hospitals in order to deliver patients to hospitals with higher-level resources for advanced treatment options. One of the most contentious issues in these plans is the “bypass time”_time allowed for EMS to bypass one hospital in order to transport to a hospital with presumed higher level stroke care. Hypothesis: Incorporating transport times and individual hospital door-to-needle times (DNTs) into regional pre-hospital triage bypass plans will expedite regional treatment times which may lead to improved patient outcomes at the system level. Methods: To minimize onset-to-needle times (ONTs), it is essential not only to find the fastest route to the nearest capable hospital, but to find the nearest capable hospital with the shortest DNTs. We examined specific time components comprising ONT, including Onset-to-Arrival times (OATs) and DNTs using Get-with-the-Guidelines data (GWTG), comparing the hospital with fastest DTN times (Hospital A) with that of the average in the St. Louis metropolitan area. Results: Hospital A had a mean DNT that was 20 min faster than the average St. Louis DNT (31 min vs. 51 min, p<.0.001), while OATs were not different. This 20 min advantage might be translated into a longer bypass time specifically for hospital A, to provide equivalent or faster ONTs for patients in the region. Conclusion: The incorporation of hospital DNTs into regional pre-hospital triage plans can individualize bypass times for each hospital. This practice may accelerate treatment times throughout a region, and could be trialed with the aid of web-based smartphone application that could provide EMS with important information that could minimize both transport times and DNTs.

Stressful Life Events as a Trigger for Autoimmune Disease? A Case Report on Mucous Membrane Pemphigoid

Dental Update ◽  
2021 ◽  
Vol 48 (5) ◽  
pp. 379-382
Author(s):  
Robert Devine ◽  
Melanie Simms
Keyword(s):  
Mucous Membrane ◽  
Patient Outcomes ◽  
Stressful Life Events ◽  
Treatment Options ◽  
Rare Condition ◽  
Corticosteroid Treatment ◽  
Diagnostic Tools ◽  
Mucous Membrane Pemphigoid ◽  
Acute Presentation

This case discusses the acute presentation of a patient with mucous membrane pemphigoid to an emergency dental department. Mucous membrane pemphigoid is a rare condition, but its presentation can be severe and concerning for both the patient and clinician. The case presents the manifestations of florid desquamative gingivitis and extensive mucosal erosions due to burst bullae. We discuss the possible causes of the condition in this patient, likely to be the stress of recent cardiac surgery, as well as exploring the efficacy of diagnostic tools, treatment options and adverse effects of corticosteroid treatment. CPD/Clinical Relevance: Correct and timely diagnosis of vesiculobullous disorders has notable impacts on patient outcomes and quality of life.

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