Coronavirus disease 2019 (COVID-19) interacts with the nervous system directly and indirectly by ... more Coronavirus disease 2019 (COVID-19) interacts with the nervous system directly and indirectly by affecting the activation of the immune system. Guillain–Barré syndrome (GBS) is triggered by an inappropriate immune system activation that overlaps with the neurotoxic mechanism of an invading pathogen. Here, we discuss the complexity of an abnormal immune system response leading to the generation of autoimmunity in the setting of acute viral infection. A 67-year-old male patient with COVID-19 developed a sensory motor acute polyneuropathy with respiratory failure. Several serum inflammatory and neurodegeneration markers were collected during hospital days 1, 3, 8, and 67 and compared to healthy individuals. Neural cell adhesion molecule 1 (NCAM-1) and neurofilament light chain (NfL) values were highly variable when compared to healthy individuals, but not to the reference COVID-19 group. We focused our attention on NCAM-1 as a possible target for antibodies directed at COVID-19 in silico.
Background: Conflicting data exists surrounding whether or not the effect of clopidogrel on risk ... more Background: Conflicting data exists surrounding whether or not the effect of clopidogrel on risk reduction of cardiovascular outcomes, including stroke, is more pronounced in smokers. The aim of this study was to determine the effect of smoking status on subsequent stroke risk in all patients with minor ischemic stroke or TIA, as well as subgroups that may be particularly impacted by an effect, and determine whether smoking improves the effect of clopidogrel treatment on subsequent stroke risk reduction. Subgroup analysis included those of older age, black race, and female gender, as these groups may have higher risk of clopidogrel non-response and subsequently poor outcomes. Methods: This was a post-hoc analysis of the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial. The POINT trial compared clopidogrel plus aspirin (DAPT) to aspirin alone for prevention of recurrent stroke, myocardial infarction, or vascular death within 3 months of a high-risk TIA or minor ischemic stroke. We used multivariable cox-regression models to determine the effect of smoking on the efficacy of DAPT in reducing the risk of subsequent ischemic stroke in all patients and prespecified subgroups stratified based on age, sex, race, and diabetes. We also performed interaction analyses to determine whether the effect of clopidogrel on subsequent ischemic stroke differed with respect to smoking status. Results: Data from 4,877 participants enrolled in the POINT trial were analyzed. Among these, 1,004 were current smokers and 3,873 were non-smokers. Smoking was associated with a non-significantly increased risk of recurrent ischemic stroke during follow up (hazard ratio, 1.31 [95% CI, 0.97 - 1.78], P=0.076). The effect of clopidogrel on ischemic stroke was not significantly different in non-smokers (hazard ratio, 0.74 [95% CI, 0.56 - 0.98], P=0.03) compared to smokers (adjusted hazard ratio, 0.63 [95% CI, 0.37 - 1.05], P=0.078), P for interaction = 0.572. In addition, the effect of clopidogrel on major hemorrhage was not significantly different in current smokers (hazard ratio, 2.59 [95% CI, 1.08 - 6.21], P=0.032) compared to non-smokers (hazard ratio, 1.67 [95% CI, 0.40 - 7.00], P=0.481), P for interaction = 0.613. This finding was maintained across different subgroups: males, females, blacks, whites, those with and without diabetes, and those aged < 60 and ≥ 60 years. Conclusions: Cigarette smoking was associated with a non-significantly higher risk of subsequent ischemic stroke and smoking did not modify the effect of clopidogrel-based dual antiplatelet therapy on subsequent ischemic stroke risk reduction, even in the subgroups of stratified based on age, sex, race, and diabetes, where greater likelihood of effect was theorized. Every effort should be made to encourage tobacco dependence treatment and cessation in patients with minor ischemic stroke and TIA.
Background: Coronavirus Disease 2019 (COVID-19) has no known specific treatments. However, there ... more Background: Coronavirus Disease 2019 (COVID-19) has no known specific treatments. However, there might be in vitro and early clinical data as well as evidence from Severe Acute Respiratory Syndrome and Middle Eastern Respiratory Syndrome that could inform clinicians and researchers. This systematic review aims to create priorities for future research of drugs repurposed for COVID-19. Methods: This systematic review will include in vitro, animal, and clinical studies evaluating the efficacy of a list of 34 specific compounds and four groups of drugs identified in a previous scoping review. Studies will be identified both from traditional literature databases and pre-print servers. Outcomes assessed will include time to clinical improvement, time to viral clearance, mortality, length of hospital stay, and proportions transferred to the intensive care unit and intubated, respectively. We will use the GRADE methodology to assess the quality of the evidence. Discussion: The challenge pos...
Coronavirus disease 2019 (COVID-19) interacts with the nervous system directly and indirectly by ... more Coronavirus disease 2019 (COVID-19) interacts with the nervous system directly and indirectly by affecting the activation of the immune system. Guillain–Barré syndrome (GBS) is triggered by an inappropriate immune system activation that overlaps with the neurotoxic mechanism of an invading pathogen. Here, we discuss the complexity of an abnormal immune system response leading to the generation of autoimmunity in the setting of acute viral infection. A 67-year-old male patient with COVID-19 developed a sensory motor acute polyneuropathy with respiratory failure. Several serum inflammatory and neurodegeneration markers were collected during hospital days 1, 3, 8, and 67 and compared to healthy individuals. Neural cell adhesion molecule 1 (NCAM-1) and neurofilament light chain (NfL) values were highly variable when compared to healthy individuals, but not to the reference COVID-19 group. We focused our attention on NCAM-1 as a possible target for antibodies directed at COVID-19 in silico.
Background: Conflicting data exists surrounding whether or not the effect of clopidogrel on risk ... more Background: Conflicting data exists surrounding whether or not the effect of clopidogrel on risk reduction of cardiovascular outcomes, including stroke, is more pronounced in smokers. The aim of this study was to determine the effect of smoking status on subsequent stroke risk in all patients with minor ischemic stroke or TIA, as well as subgroups that may be particularly impacted by an effect, and determine whether smoking improves the effect of clopidogrel treatment on subsequent stroke risk reduction. Subgroup analysis included those of older age, black race, and female gender, as these groups may have higher risk of clopidogrel non-response and subsequently poor outcomes. Methods: This was a post-hoc analysis of the Platelet Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial. The POINT trial compared clopidogrel plus aspirin (DAPT) to aspirin alone for prevention of recurrent stroke, myocardial infarction, or vascular death within 3 months of a high-risk TIA or minor ischemic stroke. We used multivariable cox-regression models to determine the effect of smoking on the efficacy of DAPT in reducing the risk of subsequent ischemic stroke in all patients and prespecified subgroups stratified based on age, sex, race, and diabetes. We also performed interaction analyses to determine whether the effect of clopidogrel on subsequent ischemic stroke differed with respect to smoking status. Results: Data from 4,877 participants enrolled in the POINT trial were analyzed. Among these, 1,004 were current smokers and 3,873 were non-smokers. Smoking was associated with a non-significantly increased risk of recurrent ischemic stroke during follow up (hazard ratio, 1.31 [95% CI, 0.97 - 1.78], P=0.076). The effect of clopidogrel on ischemic stroke was not significantly different in non-smokers (hazard ratio, 0.74 [95% CI, 0.56 - 0.98], P=0.03) compared to smokers (adjusted hazard ratio, 0.63 [95% CI, 0.37 - 1.05], P=0.078), P for interaction = 0.572. In addition, the effect of clopidogrel on major hemorrhage was not significantly different in current smokers (hazard ratio, 2.59 [95% CI, 1.08 - 6.21], P=0.032) compared to non-smokers (hazard ratio, 1.67 [95% CI, 0.40 - 7.00], P=0.481), P for interaction = 0.613. This finding was maintained across different subgroups: males, females, blacks, whites, those with and without diabetes, and those aged < 60 and ≥ 60 years. Conclusions: Cigarette smoking was associated with a non-significantly higher risk of subsequent ischemic stroke and smoking did not modify the effect of clopidogrel-based dual antiplatelet therapy on subsequent ischemic stroke risk reduction, even in the subgroups of stratified based on age, sex, race, and diabetes, where greater likelihood of effect was theorized. Every effort should be made to encourage tobacco dependence treatment and cessation in patients with minor ischemic stroke and TIA.
Background: Coronavirus Disease 2019 (COVID-19) has no known specific treatments. However, there ... more Background: Coronavirus Disease 2019 (COVID-19) has no known specific treatments. However, there might be in vitro and early clinical data as well as evidence from Severe Acute Respiratory Syndrome and Middle Eastern Respiratory Syndrome that could inform clinicians and researchers. This systematic review aims to create priorities for future research of drugs repurposed for COVID-19. Methods: This systematic review will include in vitro, animal, and clinical studies evaluating the efficacy of a list of 34 specific compounds and four groups of drugs identified in a previous scoping review. Studies will be identified both from traditional literature databases and pre-print servers. Outcomes assessed will include time to clinical improvement, time to viral clearance, mortality, length of hospital stay, and proportions transferred to the intensive care unit and intubated, respectively. We will use the GRADE methodology to assess the quality of the evidence. Discussion: The challenge pos...
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Papers by Adam Lang