scholarly journals SARS-CoV-2 Viremia is Associated with Distinct Proteomic Pathways and Predicts COVID-19 Outcomes

2021 ◽  
Author(s):  
Yijia Li ◽  
Alexis M Schneider ◽  
Arnav Mehta ◽  
Moshe Sade-Feldman ◽  
Kyle R Kays ◽  
...  
Keyword(s):  
Tissue Damage ◽  
Severe Disease ◽  
Small Scale ◽  
Plasma Viremia ◽  
Proteomic Data ◽  
Disease Outcomes ◽  
Time Of Presentation ◽  
Acid Test ◽  
The Relationship ◽  
Proximity Extension Assay

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) plasma viremia has been associated with severe disease and death in coronavirus disease 2019 (COVID-19) in small-scale cohort studies. The mechanisms behind this association remain elusive. Methods: We evaluated the relationship between SARS-CoV-2 viremia, disease outcome, inflammatory and proteomic profiles in a cohort of COVID-19 emergency department participants. SARS-CoV-2 viral load was measured using qRT-PCR based platform. Proteomic data were generated with Proximity Extension Assay (PEA) using the Olink platform. Results: Three hundred participants with nucleic acid test-confirmed COVID-19 were included in this study. Levels of plasma SARS-CoV-2 viremia at the time of presentation predicted adverse disease outcomes, with an adjusted odds ratio (aOR) of 10.6 (95% confidence interval [CI] 4.4, 25.5, P<0.001) for severe disease (mechanical ventilation and/or 28-day mortality) and aOR of 3.9 (95%CI 1.5, 10.1, P=0.006) for 28-day mortality. Proteomic analyses revealed prominent proteomic pathways associated with SARS-CoV-2 viremia, including upregulation of SARS-CoV-2 entry factors (ACE2, CTSL, FURIN), heightened markers of tissue damage to the lungs, gastrointestinal tract, endothelium/vasculature and alterations in coagulation pathways. Conclusions: These results highlight the cascade of vascular and tissue damage associated with SARS-CoV-2 plasma viremia that underlies its ability to predict COVID-19 disease outcomes.

scholarly journals Diabetes and COVID19: a bidirectional relationship

2021 ◽  
Author(s):  
Ranjit Unnikrishnan ◽  
Anoop Misra
Keyword(s):  
Clinical Care ◽  
Severe Disease ◽  
Respiratory Involvement ◽  
Pancreatic Damage ◽  
Increased Risk ◽  
Bidirectional Relationship ◽  
Rapid Spread ◽  
Relationship Of ◽  
The Relationship ◽  
New Onset

AbstractThe advent and rapid spread of the coronavirus disease-2019 (COVID19) pandemic across the world has focused attention on the relationship of commonly occurring comorbidities such as diabetes on the course and outcomes of this infection. While diabetes does not seem to be associated with an increased risk of COVID19 infection per se, it has been clearly demonstrated that the presence of hyperglycemia of any degree predisposes to worse outcomes, such as more severe respiratory involvement, ICU admissions, need for mechanical ventilation and mortality. Further, COVID19 infection has been associated with the development of new-onset hyperglycemia and diabetes, and worsening of glycemic control in pre-existing diabetes, due to direct pancreatic damage by the virus, body’s stress response to infection (including cytokine storm) and use of diabetogenic drugs such as corticosteroids in the treatment of severe COVID19. In addition, public health measures taken to flatten the pandemic curve (such as lockdowns) can also adversely impact persons with diabetes by limiting their access to clinical care, healthy diet, and opportunities to exercise. Most antidiabetic medications can continue to be used in patients with mild COVID19 but switching over to insulin is preferred in severe disease.

scholarly journals Maternal toxoplasmosis and the risk of childhood autism: serological and molecular small-scale studies

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jamila S. Al Malki ◽  
Nahed Ahmed Hussien ◽  
Fuad Al Malki
Keyword(s):  
Neurodevelopmental Disorders ◽  
Repetitive Behavior ◽  
Saudi Arabian ◽  
Childhood Autism ◽  
Small Scale ◽  
Autistic Children ◽  
High Prevalence ◽  
Life Threatening ◽  
The Relationship ◽  
Delayed Language Development

Abstract Background Toxoplasmosis resulting from infection with the Toxoplasma parasite has become an endemic disease worldwide. Recently, a few studies have reported a high prevalence of Toxoplasmosis infections among Saudi Arabian women. This disease could become life threatening for pregnant women and for immunodeficient people. There is evidence that infections during pregnancy, especially in the early stages, are associated with neurodevelopmental disorders. Autism disorder represents one of the most common neurodevelopmental disorders worldwide; it is associated with delayed language development, weak communication interaction, and repetitive behavior. The relationship between prenatal toxoplasmosis and autism in childhood remains unclear. The present study aims to report a link between maternal toxoplasmosis and autistic offspring among Saudi Arabian women. Method Blood samples (36 maternal, 36 from their non-autistic children, and 36 from their autistic children) were collected for serological and molecular evaluation. Results A toxoplasmosis infection was reported for 33.34% of participants using an ELISA assay (5.56% IgG+/IgM+, 11.11% IgG−/IgM+, and 16.67% IgG+/IgM-); however, a nested PCR assay targeting B1 toxoplasmosis specific genes recorded positive tests for 80.56% of the samples. In addition, the present study detected several points of mutation of mtDNA including NADH dehydrogenase (ND1, ND4) and Cyt B genes and the nDNA pyruvate kinase (PK) gene for autistic children infected with toxoplasmosis. Conclusion Considering previous assumptions, we suggest that a maternal toxoplasmosis infection could have a role in the development of childhood autism linked to mtDNA and nDNA impairment.

scholarly journals Diabetes and COVID19: a bidirectional relationship

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ranjit Unnikrishnan ◽  
Anoop Misra
Keyword(s):  
Clinical Care ◽  
Severe Disease ◽  
Respiratory Involvement ◽  
Pancreatic Damage ◽  
Increased Risk ◽  
Bidirectional Relationship ◽  
Rapid Spread ◽  
Relationship Of ◽  
The Relationship ◽  
New Onset

AbstractThe advent and rapid spread of the coronavirus disease-2019 (COVID19) pandemic across the world has focused attention on the relationship of commonly occurring comorbidities such as diabetes on the course and outcomes of this infection. While diabetes does not seem to be associated with an increased risk of COVID19 infection per se, it has been clearly demonstrated that the presence of hyperglycemia of any degree predisposes to worse outcomes, such as more severe respiratory involvement, ICU admissions, need for mechanical ventilation and mortality. Further, COVID19 infection has been associated with the development of new-onset hyperglycemia and diabetes, and worsening of glycemic control in pre-existing diabetes, due to direct pancreatic damage by the virus, body’s stress response to infection (including cytokine storm) and use of diabetogenic drugs such as corticosteroids in the treatment of severe COVID19. In addition, public health measures taken to flatten the pandemic curve (such as lockdowns) can also adversely impact persons with diabetes by limiting their access to clinical care, healthy diet, and opportunities to exercise. Most antidiabetic medications can continue to be used in patients with mild COVID19 but switching over to insulin is preferred in severe disease.

Abstract P777: Statistical Modeling of Proteomic Signaling During Stroke in Patients Undergoing Thrombectomy

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Sydney Claypoole ◽  
Jacqueline Frank ◽  
Madison Sands ◽  
Christopher J McLouth ◽  
Jill Roberts ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Statistical Modeling ◽  
Internal Control ◽  
Stepwise Regression ◽  
Infarct Volume ◽  
Tissue Samples ◽  
Bivariate Regression ◽  
Inflammatory Proteins ◽  
The Relationship ◽  
Proximity Extension Assay

Introduction: The previously published Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) protocol (clinicaltrials.gov NCT03153683) utilizes mechanical thrombectomy to obtain tissue samples for banking. Peripheral blood proximal to the clot and intracranial blood distal from the clot were isolated. Proteomic and statistical analyses revealed normalized (intracranial-systemic) CCL19 expression was a predictor of infarct volume. Statistical modeling analyses were used determine the CCL19-associated proteomic signaling network occurring during ischemic stroke relating to infarct volume. Methods: Arterial intracranial and systemic blood samples underwent analysis for inflammatory proteins using Proximity Extension Assay (PEA) via Olink (Olink Proteomics, Boston, MA). Systemic expression was used as an internal control to normalize expression in the intracranial blood. Bivariate regression was used to examine the relationship between the intracranial normalized CCL19 expression and infarct volume. A backwards stepwise regression was then used to determine a model of predictability of infarct volume by CCL19 and associated inflammatory proteins. Results: 25 subjects (>18 yrs) with a mean infarct volume of 8,172 ± 82,284 mm 3 and mean infarct time of 513 ± 246 minutes were included in this study. Their median age was 64 (24-91) and 10 (40%) were male. 16 subjects (64%) had hypertension, 15 (60%) had BMI > 25, and 6 (24%) had a previous stroke. The stepwise regression model shows normalized expression of 16 proteins correlated with an increase in infarct volume (p<0.005): CCL20, CXCL1, OSM, CD6, OSMR, TGF-alpha, TRANCE, CXCL10, LIF-R, CCL19, CDCP1, Flt3L, CCL23, CD244, TRAIL, NOTCH1. Conclusions: In our model, the expression of these proteins were consistently changed, though the directionality differed. LIF-R, NOTCH1, TRAIL, CD6, CCL23, TGF-alpha, and CCL20 were positively correlated, while the expressions of Flt3L, OSM, OSMR, TRANCE, CD244, CDCP1, CXCL1, CXCL10, and CCL19 were negatively correlated with infarct volume. This model depicts the proteomic signaling occurring during stroke in relationship to infarct volume, which reveals potential biomarkers and therapeutic targets for the early phase of ischemic stroke.

The association of lumbosacral transitional vertebral anomalies with acetabular dysplasia in adult patients with hip-spine syndrome

2021 ◽  
Vol 103-B (8) ◽  
pp. 1351-1357
Author(s):  
Joshua Sun ◽  
Avneesh Chhabra ◽  
Uma Thakur ◽  
Louis Vazquez ◽  
Yin Xi ◽  
...  
Keyword(s):  
Acetabular Dysplasia ◽  
Intraclass Correlation ◽  
Final Diagnosis ◽  
Hip Pain ◽  
Pars Interarticularis ◽  
Vertebral Anomalies ◽  
Lumbosacral Transitional Vertebra ◽  
Standard Radiographs ◽  
Time Of Presentation ◽  
The Relationship

Aims Some patients presenting with hip pain and instability and underlying acetabular dysplasia (AD) do not experience resolution of symptoms after surgical management. Hip-spine syndrome is a possible underlying cause. We hypothesized that there is a higher frequency of radiological spine anomalies in patients with AD. We also assessed the relationship between radiological severity of AD and frequency of spine anomalies. Methods In a retrospective analysis of registry data, 122 hips in 122 patients who presented with hip pain and and a final diagnosis of AD were studied. Two observers analyzed hip and spine variables using standard radiographs to assess AD. The frequency of lumbosacral transitional vertebra (LSTV), along with associated Castellvi grade, pars interarticularis defect, and spinal morphological measurements were recorded and correlated with radiological severity of AD. Results Out of 122 patients, 110 (90.2%) were female and 12 (9.8%) were male. We analyzed the radiographs of 122 hips (59 (48.4%) symptomatic left hips, and 63 (51.6%) symptomatic right hips). Average age at time of presentation was 34.2 years (SD 11.2). Frequency of LSTV was high (39% to 43%), compared to historic records from the general population, with Castellvi type 3b being the most common (60% to 63%). Patients with AD have increased L4 and L5 interpedicular distance compared to published values. Frequency of pars interarticularis defect was 4%. Intraclass correlation coefficient for hip and spine variables assessed ranged from good (0.60 to 0.75) to excellent (0.75 to 1.00). Severity of AD did not demonstrate significant correlation with frequency of radiological spine anomalies. Conclusion Patients with AD have increased frequency of spinal anomalies seen on standard hip radiographs. However, there exists no correlation between radiological severity of AD and frequency of spine anomalies. In managing AD patients, clinicians should also assess spinal anomalies that are easily found on standard hip radiographs. Cite this article: Bone Joint J 2021;103-B(8):1351–1357.

scholarly journals MYELODYSPLASTIC SYNDROMES AND IRON CHELATION THERAPY

2017 ◽  
Vol 9 (1) ◽  
pp. e2017021 ◽  
Author(s):  
Emanuele Angelucci ◽  
Silvana Anna Maria Urru ◽  
Federica Pilo ◽  
Alberto Piperno
Keyword(s):  
Iron Overload ◽  
Myelodysplastic Syndromes ◽  
Tissue Damage ◽  
Clinical Evidence ◽  
New Technologies ◽  
Iron Chelation ◽  
Organ Damage ◽  
Evidence Base ◽  
Toxic Damage ◽  
The Relationship

Over recent decades we have been fortunate to witness the advent of new technologies and of an expanded knowledge and application of chelation therapies to the benefit of patients with iron overload. However, extrapolation of learnings from thalassemia to the myelodysplastic syndromes (MDS) has resulted in a fragmented and uncoordinated clinical evidence base. We’re therefore forced to change our understanding of MDS, looking with other eyes to observational studies that inform us about the relationship between iron and tissue damage in these subjects. The available evidence suggests that iron accumulation is prognostically significant in MDS, but levels of accumulation historically associated with organ damage (based on data generated in the thalassemias) are infrequent. Emerging experimental data have provided some insight into this paradox, as our understanding of iron-induced tissue damage has evolved from a process of progressive bulking of organs through high-volumes iron deposition, to one of ‘toxic’ damage inflicted through multiple cellular pathways. Damage from iron may therefore occur prior to reaching reference thresholds, and similarly, chelation may be of benefit before overt iron overload is seen. In this review, we revisit the science and clinical evidence for iron overload in MDS to better characterise the iron overload phenotype in these patients, which is distinct from the classical transfusional and non-transfusional iron overload syndrome. We hope this will provide a conceptual framework to better understand the complex associations between anemia, iron and clinical outcomes, to accelerate progress in this area.

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