•Review of stimulation and recording techniques for cutaneous silent period (CSP).•Review of functional anatomy, neurophysiology, and neuropharmacology of CSPs.•Understanding principles of CSP ...testing is fundamental for its clinical application.
Testing of exteroceptive electromyographic modulation of ongoing voluntary muscle activity is of interest in normal human physiology and in diagnostic clinical neurophysiology in normal and pathological conditions. The cutaneous silent period (CSP) is a robust and reproducible nociceptive EMG suppression, mediated at the spinal level by small-diameter A-delta afferents. This critical review surveys the literature on applied stimulation and recording techniques, physiological principles, involved fiber types, spinal circuitry, supraspinal modulation, neurotransmitters and pharmacology of CSPs. Understanding the principles of CSP testing is fundamental for a valid and thoughtful clinical application of CSPs (reviewed in part 2) (Kofler et al., 2019).
Background. Reported allergy to beta-lactam antibiotics is common and often leads to unnecessary avoidance in patients who could tolerate these antibiotics. We prospectively evaluated the impact of ...these reported allergies on clinical outcomes. Methods. We conducted a trainee-led prospective cohort study to determine the burden and clinical impact of reported beta-lactam allergy on patients seen by infectious diseases consultation services at 3 academic hospitals. The primary outcome was a composite measure of readmission for the same infection, acute kidney injury, Clostridium difficile infection, or drug-related adverse reactions requiring discontinuation. Predictors of interest were history of beta-lactam allergy and receipt of preferred beta-lactam therapy. Results. Among 507 patients, 95 (19%) reported beta-lactam allergy; preferred therapy was a beta-lactam in 72 (76%). When betalactam therapy was preferred, 25 (35%) did not receive preferred therapy due to their report of allergy even though 13 (52%) reported non-severe prior reactions. After adjustment for confounders, patients who did not receive preferred beta-lactam therapy were at greater risk of adverse events (adjusted odds ratio aOR, 3.1; 95% confidence interval CI, 1.28–7.89) compared with those without reported allergy. In contrast, patients who received preferred beta-lactam therapy had a similar risk of adverse events compared with patients not reporting allergy (aOR, 1.33; 95% CI, .62–2.87). Conclusions. Avoidance of preferred beta-lactam therapy in patients who report allergy is associated with an increased risk of adverse events. Development of inpatient programs aimed at accurately identifying beta-lactam allergies to safely promote beta-lactam administration among these patients is warranted.
•Review of pathophysiology and clinical utility of cutaneous silent periods (CSPs).•CSP testing may aid in the evaluation of small-diameter fibers.•Most useful in intramedullary spinal cord ...dysfunctions and small fiber neuropathies.
Testing of exteroceptive electromyographic modulation of ongoing voluntary muscle activity is of increasing interest as a diagnostic tool in clinical neurophysiology. The cutaneous silent period (CSP) is a robust and reproducible nociceptive EMG suppression, mediated at the spinal level by small-diameter A-delta afferents. The techniques and physiological principles of CSP testing, which are a fundamental prerequisite for a valid and thoughtful clinical application, are reviewed separately in part 1 (Kofler et al., 2019). This comprehensive review surveys the literature on pathophysiological conditions in which CSPs have been reported, and aims at a critical overview on the clinical utility of CSP testing. The most useful clinical applications seem to be the functional diagnostics of intramedullary, in particular centromedullary, dysfunctions, and the assessment of small fiber neuropathies, in particular those affecting A-delta fibers. CSPs have in addition been studied in a variety of movement disorders and in neuropathic pain and other painful conditions, including fibromyalgia.
West Nile virus (WNV) is the most common mosquito-borne virus in North America. WNV-associated neuroinvasive disease affects all ages, although elderly and immunocompromised individuals are ...particularly at risk. WNV neuroinvasive disease has killed over 2300 Americans since WNV entered into the United States in the New York City outbreak of 1999. Despite 20 years of intensive laboratory and clinical research, there are still no approved vaccines or antivirals available for human use. However, rapid progress has been made in both understanding the pathogenesis of WNV and treatment in clinical practices. This review summarizes our current understanding of WNV infection in terms of human clinical manifestations, host immune responses, neuroinvasion, and therapeutic interventions.
•Coronaviruses represent a significant burden in acute care settings.•Female gender and smoking were associated with poor prognosis.•All cause mortality in our cohort was similar to what is observed ...for influenza virus.
The World Health Organization has highlighted the need for improved surveillance and understanding of the health burden imposed by non-influenza RNA respiratory viruses. Human coronaviruses (CoVs) are a major cause of respiratory and gastrointestinal tract infections with associated morbidity and mortality.
The objective of our study was to characterize the epidemiology of CoVs in our tertiary care centre, and identify clinical correlates of disease severity.
A cross-sectional study was performed of 226 patients admitted with confirmed CoV respiratory tract infection between 2010 and 2016. Variables consistent with a severe disease burden were evaluated including symptoms, length of stay, intensive care unit (ICU) admission and mortality.
CoVs represented 11.3% of all positive respiratory virus samples and OC43 was the most commonly identified CoV. The majority of infections were community-associated while 21.6% were considered nosocomial. The average length of stay was 11.8 days with 17.3% of patients requiring ICU admission and an all-cause mortality of 7%. In a multivariate model, female gender and smoking were associated with increased likelihood of admission to ICU or death.
This study highlights the significant burden of CoVs and justifies the need for surveillance in the acute care setting.
In a cohort of patients with acute aspiration pneumonitis, antibiotics within 48 hours of macroaspiration was not associated with reduced mortality compared to supportive care only, yet resulted in ...the need for more frequent antibiotic escalation and fewer antibiotic-free days.
Abstract
Background
Prophylactic antimicrobial therapy is frequently prescribed for acute aspiration pneumonitis, with the intent of preventing the development of aspiration pneumonia. However, few clinical studies have examined the benefits and harms of this practice.
Methods
A retrospective cohort study design was used to compare outcomes of patients with aspiration pneumonitis who received prophylactic antimicrobial therapy with those managed with supportive care only during the initial 2 days following macroaspiration. The primary outcome was in-hospital mortality within 30 days. Secondary outcomes included transfer to critical care and antimicrobial therapy received between days 3 and 14 following macroaspiration including escalation of therapy and antibiotic-free days.
Results
Among 1483 patients reviewed, 200 met the case definition for acute aspiration pneumonitis, including 76 (38%) who received prophylactic antimicrobial therapy and 124 (62%) who received supportive management only. After adjusting for patient-level predictors, antimicrobial prophylaxis was not associated with any improvement in mortality (odds ratio, 0.9; 95% confidence interval CI, 0.4-1.7; P = .7). Patients receiving prophylactic antimicrobial therapy were no less likely to require transfer to critical care (5% vs 6%; P = .7) and subsequently received more frequent escalation of antibiotic therapy (8% vs 1%; P = .002) and fewer antibiotic-free days (7.5 vs 10.9; P < .0001).
Conclusions
Prophylactic antimicrobial therapy for patients with acute aspiration pneumonitis does not offer clinical benefit and may generate antibiotic selective pressures that results in the need for escalation of antibiotic therapy among those who develop aspiration pneumonia.
More than twenty years following the end of the 1990-1991 Gulf War it is estimated that approximately 300,000 veterans of this conflict suffer from an unexplained chronic, multi-system disorder known ...as Gulf War Illness (GWI). The etiology of GWI may be exposure to chemical toxins, but it remains only partially defined, and its case definition is based only on symptoms. Objective criteria for the diagnosis of GWI are urgently needed for diagnosis and therapeutic research.
This study was designed to determine if blood biomarkers could provide objective criteria to assist diagnosis of GWI.
A surveillance study of 85 Gulf War Veteran volunteers identified from the Department of Veterans Affairs Minnesota Gulf War registry was performed. All subjects were deployed to the Gulf War. Fifty seven subjects had GWI defined by CDC criteria, and 28 did not have symptomatic criteria for a diagnosis of GWI. Statistical analyses were performed on peripheral blood counts and assays of 61 plasma proteins using the Mann-Whitney rank sum test to compare biomarker distributions and stepwise logistic regression to formulate a diagnostic model.
Lymphocyte, monocyte, neutrophil, and platelet counts were higher in GWI subjects. Six serum proteins associated with inflammation were significantly different in GWI subjects. A diagnostic model of three biomarkers-lymphocytes, monocytes, and C reactive protein-had a predicted probability of 90% (CI 76-90%) for diagnosing GWI when the probability of having GWI was above 70%.
The results of the current study indicate that inflammation is a component of the pathobiology of GWI. Analysis of the data resulted in a model utilizing three readily measurable biomarkers that appears to significantly augment the symptom-based case definition of GWI. These new observations are highly relevant to the diagnosis of GWI, and to therapeutic trials.
West Nile virus (WNV) infection has been reported to promote myasthenia gravis (MG) and various other diseases that have a presumed autoimmune pathogenesis. Molecular mimicry between WNV proteins and ...host proteins has been postulated as the major mechanism for WNV-triggered breaking of immunological self-tolerance. We present a patient with stable ocular MG and positive anti-acetylcholine receptor antibodies who progressed to myasthenic crisis after WNV neuroinvasive disease. In this case of stable autoimmune disease with proven auto-antibodies, transformation to generalized disease cannot be attributed to molecular mimicry, which requires that an immune response first be generated against an infectious agent. Rather, the evidence supports the concept of a post-infectious pro-inflammatory state that may contribute to the amplification and promotion of autoimmune disease in some WNV survivors.
•West Nile virus (WNV) infection has been reported to promote myasthenia gravis (MG) and other autoimmune diseases.•Molecular mimicry between WNV proteins and host proteins is postulated as the major mechanism for WNV-triggered autoimmunity.•We present a patient with stable ocular MG who progressed to myasthenic crisis after WNV neuroinvasive disease.•In stable ocular MG with proven autoantibodies, transformation to generalized MG cannot be attributed to molecular mimicry.•Evidence implicates a WNV-induced post-infectious pro-inflammatory state that may amplify and promote autoimmune disease.
CD8
T cells are crucial components of immunity and play a vital role in recovery from West Nile virus (WNV) infection. Here, we identify a previously unrecognized function of interleukin-17A (IL-17A) ...in inducing cytotoxic-mediator gene expression and promoting CD8
T cell cytotoxicity against WNV infection in mice. We find that IL-17A-deficient (Il17a
) mice are more susceptible to WNV infection and develop a higher viral burden than wild-type (WT) mice. Interestingly, the CD8
T cells isolated from Il17a
mice are less cytotoxic and express lower levels of cytotoxic-mediator genes, which can be restored by supplying recombinant IL-17A in vitro and in vivo Importantly, treatment of WNV-infected mice with recombinant IL-17A, as late as day 6 postinfection, significantly reduces the viral burden and increases survival, suggesting a therapeutic potential for IL-17A. In conclusion, we report a novel function of IL-17A in promoting CD8
T cell cytotoxicity, which may have broad implications in other microbial infections and cancers.
Interleukin-17A (IL-17A) and CD8
T cells regulate diverse immune functions in microbial infections, malignancies, and autoimmune diseases. IL-17A is a proinflammatory cytokine produced by diverse cell types, while CD8
T cells (known as cytotoxic T cells) are major cells that provide immunity against intracellular pathogens. Previous studies have demonstrated a crucial role of CD8
T cells in recovery from West Nile virus (WNV) infection. However, the role of IL-17A during WNV infection remains unclear. Here, we demonstrate that IL-17A protects mice from lethal WNV infection by promoting CD8
T cell-mediated clearance of WNV. In addition, treatment of WNV-infected mice with recombinant IL-17A reduces the viral burden and increases survival of mice, suggesting a potential therapeutic. This novel IL-17A-CD8
T cell axis may also have broad implications for immunity to other microbial infections and cancers, where CD8
T cell functions are crucial.
Vaccination studies in the hemodialysis population have demonstrated decreased antibody response compared with healthy controls, but vaccine effectiveness for preventing SARS-CoV-2 infection and ...severe disease is undetermined.
We conducted a retrospective cohort study in the province of Ontario, Canada, between December 21, 2020, and June 30, 2021. Receipt of vaccine, SARS-CoV-2 infection, and related severe outcomes (hospitalization or death) were determined from provincial health administrative data. Receipt of one and two doses of vaccine were modeled in a time-varying cause-specific Cox proportional hazards model, adjusting for baseline characteristics, background community infection rates, and censoring for non-COVID death, recovered kidney function, transfer out of province, solid organ transplant, and withdrawal from dialysis.
Among 13,759 individuals receiving maintenance dialysis, 2403 (17%) were unvaccinated and 11,356 (83%) had received at least one dose by June 30, 2021. Vaccine types were BNT162b2 (
=8455, 74%) and mRNA-1273 (
=2901, 26%); median time between the first and second dose was 36 days (IQR 28-51). The adjusted hazard ratio (HR) for SARS-CoV-2 infection and severe outcomes for one dose compared with unvaccinated was 0.59 (95% CI, 0.46 to 0.76) and 0.54 (95% CI, 0.37 to 0.77), respectively, and for two doses compared with unvaccinated was 0.31 (95% CI, 0.22 to 0.42) and 0.17 (95% CI, 0.1 to 0.3), respectively. There were no significant differences in vaccine effectiveness among age groups, dialysis modality, or vaccine type.
COVID-19 vaccination is effective in the dialysis population to prevent SARS-CoV-2 infection and severe outcomes, despite concerns about suboptimal antibody responses.
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