scholarly journals Increased complement activation is a distinctive feature of severe SARS-CoV-2 infection

2021 ◽  
Vol 6 (59) ◽  
pp. eabh2259
Author(s):  
Lina Ma ◽  
Sanjaya K. Sahu ◽  
Marlene Cano ◽  
Vasanthan Kuppuswamy ◽  
Jamal Bajwa ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Distinctive Feature ◽  
Complement Activation ◽  
Invasive Mechanical Ventilation ◽  
Tertiary Care ◽  
Endothelial Injury ◽  
School Of Medicine ◽  
Tertiary Care Centers ◽  
Angiopoietin 2 ◽  
Von Willebrand

Complement activation has been implicated in the pathogenesis of severe SARS-CoV-2 infection. However, it remains to be determined whether increased complement activation is a broad indicator of critical illness (and thus, no different in COVID-19). It is also unclear which pathways are contributing to complement activation in COVID-19, and if complement activation is associated with certain features of severe SARS-CoV-2 infection, such as endothelial injury and hypercoagulability. To address these questions, we investigated complement activation in the plasma from patients with COVID-19 prospectively enrolled at two tertiary care centers: Washington University School of Medicine (n=134) and Yale School of Medicine (n=49). We compared our patients to two non-COVID cohorts: (a) patients hospitalized with influenza (n=54), and (b) patients admitted to the intensive care unit (ICU) with acute respiratory failure requiring invasive mechanical ventilation (IMV, n=22). We demonstrate that circulating markers of complement activation are elevated in patients with COVID-19 compared to those with influenza and to patients with non-COVID-19 respiratory failure. Further, the results facilitate distinguishing those who are at higher risk of worse outcomes such as requiring ICU admission, or IMV. Moreover, the results indicate enhanced activation of the alternative complement pathway is most prevalent in patients with severe COVID-19 and is associated with markers of endothelial injury (i.e., angiopoietin-2) as well as hypercoagulability (i.e., thrombomodulin and von Willebrand factor). Our findings identify complement activation to be a distinctive feature of COVID-19, and provide specific targets that may be utilized for risk prognostication, drug discovery and personalized clinical trials.

scholarly journals Increased complement activation is a distinctive feature of severe SARS-CoV-2 infection

2021 ◽  
Author(s):  
Lina Ma ◽  
Sanjaya K. Sahu ◽  
Marlene Cano ◽  
Vasanthan Kuppuswamy ◽  
Jamal Bajwa ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Distinctive Feature ◽  
Complement Activation ◽  
Alternative Pathway ◽  
Multiorgan Failure ◽  
Invasive Mechanical Ventilation ◽  
Tertiary Care ◽  
Endothelial Injury ◽  
Pathway Activation ◽  
Tertiary Care Centers

ABSTRACTComplement activation has been implicated in the pathogenesis of severe SARS-CoV-2 infection. However, it remains to be determined whether increased complement activation is a broad indicator of critical illness (and thus, no different in COVID-19). It is also unclear which pathways are contributing to complement activation in COVID-19, and, if complement activation is associated with certain features of severe SARS-CoV-2 infection, such as endothelial injury and hypercoagulability. To address these questions, we investigated complement activation in the plasma from patients with COVID-19 prospectively enrolled at two tertiary care centers. We compared our patients to two non-COVID cohorts: (a) patients hospitalized with influenza, and (b) patients admitted to the intensive care unit (ICU) with acute respiratory failure requiring invasive mechanical ventilation (IMV). We demonstrate that circulating markers of complement activation (i.e., sC5b-9) are elevated in patients with COVID-19 compared to those with influenza and to patients with non-COVID-19 respiratory failure. Further, the results facilitate distinguishing those who are at higher risk of worse outcomes such as requiring ICU admission, or IMV. Moreover, the results indicate enhanced activation of the alternative complement pathway is most prevalent in patients with severe COVID-19 and is associated with markers of endothelial injury (i.e., Ang2) as well as hypercoagulability (i.e., thrombomodulin and von Willebrand factor). Our findings identify complement activation to be a distinctive feature of COVID-19, and provide specific targets that may be utilized for risk prognostication, drug discovery and personalized clinical trials.SUMMMARYComplement has been implicated in COVID-19. However, whether this is distinctive of COVID-19 remains unanswered. Ma et al report increased complement activation in COVID-19 compared to influenza and non-COVID respiratory failure, and demonstrate alternative pathway activation as a key marker of multiorgan failure and death.

Inhaled Nitric Oxide Treatment for Stabilization and Emergency Medical Transport of Critically Ill Newborns and Infants

PEDIATRICS ◽  
1995 ◽  
Vol 95 (5) ◽  
pp. 773-776
Author(s):  
John P. Kinsella ◽  
Jeffrey M. Schmidt ◽  
Jeff Griebel ◽  
Steven H. Abman
Keyword(s):  
Nitric Oxide ◽  
Respiratory Failure ◽  
Critically Ill ◽  
Tertiary Care ◽  
Inhaled Nitric Oxide ◽  
Hypoxemic Respiratory Failure ◽  
Emergency Medical ◽  
Medical Transport ◽  
Tertiary Care Centers ◽  
Inhaled No

Stabilization and transport of critically ill newborns and infants is a vital component of regionalized care. With the advent and proliferation of new therapies for the management of severe hypoxemic respiratory failure, emergency medical transport to tertiary care centers increasingly requires novel transport innovations. Inhaled nitric oxide (NO) therapy has been used in the management of severe persistent pulmonary hypertension of newborns (PPHN) and of hypoxemic respiratory failure in older pediatric patients.1-5 We report the use of inhaled NO therapy during transport in six patients with critical hypoxemia. This report describes a practical approach to stabilization and transport of critically ill newborns and infants using inhaled NO.

scholarly journals Responsiveness of Inhaled Epoprostenol in Respiratory Failure due to COVID-19

2020 ◽  
pp. 088506662097652
Author(s):  
Rajiv Sonti ◽  
C. William Pike ◽  
Nathan Cobb
Keyword(s):  
Respiratory Failure ◽  
Rescue Therapy ◽  
A Priori ◽  
Tertiary Care ◽  
Mechanically Ventilated ◽  
Pulmonary Vasodilators ◽  
Before And After ◽  
Wide Variability ◽  
Clinically Significant ◽  
Tertiary Care Centers

Background: Inhaled pulmonary vasodilators are used as adjunctive therapies for the treatment of refractory hypoxemia. Available evidence suggest they improve oxygenation in a subset of patients without changing long-term trajectory. Given the differences in respiratory failure due to COVID-19 and “traditional” ARDS, we sought to identify their physiologic impact. Methods: This is a retrospective observational study of patients mechanically ventilated for COVID-19, from the ICUs of 2 tertiary care centers, who received inhaled epoprostenol (iEpo) for the management of hypoxemia. The primary outcome is change in PaO2/FiO2. Additionally, we measured several patient level features to predict iEpo responsiveness (or lack thereof). Results: Eighty patients with laboratory confirmed SARS-CoV2 received iEpo while mechanically ventilated and had PaO2/FiO2 measured before and after. The median PaO2/FiO2 prior to receiving iEpo was 92 mmHg and interquartile range (74 – 122). The median change in PaO2/FiO2 was 9 mmHg (-9 – 37) corresponding to a 10% improvement (-8 – 41). Fifty-percent (40 / 80) met our a priori definition of a clinically significant improvement in PaO2/FiO2 (increase in 10% from the baseline value). Prone position and lower PaO2/FiO2 when iEpo was started predicted a more robust response, which held after multivariate adjustment. For proned individuals, improvement in PaO2/FiO2 was 14 mmHg (-6 to 45) vs. 3 mmHg (-11 – 20), p = 0.04 for supine individuals; for those with severe ARDS (PaO2/FiO2 < 100, n = 49) the median improvement was 16 mmHg (-2 – 46). Conclusion: Fifty percent of patients have a clinically significant improvement in PaO2/FiO2 after the initiation of iEpo. This suggests it is worth trying as a rescue therapy; although generally the benefit was modest with a wide variability. Those who were prone and had lower PaO2/FiO2 were more likely to respond.

scholarly journals 124. Six-year Longitudinal Analysis of an Inpatient Infectious Diseases Telemedicine Service at a Community Hospital

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S191-S192
Author(s):  
Nupur Gupta ◽  
Adit B Sanghvi ◽  
John Mellors ◽  
Rima Abdel-Massih
Keyword(s):  
Infectious Disease ◽  
Tertiary Care ◽  
Medical Officer ◽  
Rural Hospital ◽  
Hospital Length Of Stay ◽  
Observation Study ◽  
Patient Acuity ◽  
Telemedicine Service ◽  
Tertiary Care Centers ◽  
Over Time

Abstract Background Telemedicine (TM) has emerged as a viable solution to extend infectious disease (ID) expertise to communities without access to this specialty.1 TM allows clinicians in rural settings to connect with specialists at distant sites and provide the best care for their patients, often eliminating the need for hospital transfers. Here, we describe the experience from one of the longest standing inpatient Tele-ID consult services using live audio-video (AV) visits with the assistance of a telepresenter. Methods Longitudinal data were collected from a 126-bed rural hospital in Pennsylvania that had no access to ID consultation before 2014. Live AV consults during business hours began in 2014 and telephonic physician to physician consults were made available 24/7. All ID consult data were extracted from the hospital electronic health record between 2014 to 2019. Key outcomes assessed included the number of consult encounters, total hospital length of stay (LOS), discharges to home, transfer to tertiary care centers, and readmission rates at 30 days. Results Most consulted patients were Caucasians, and females with an average age of 64.7 years (Table 1). The number of unique consult encounters increased annually from 111 in 2014 to 469 in 2019 (Table 1). The Charlson Comorbidity Score and Elixhauser Comorbidity Index also increased each year beginning in 2016 (Table 1). By contrast, LOS decreased each year as did the 30-day readmission rate (Table 2). Most patients were not transferred (average 89.4% over 6 years) to tertiary care centers and more than half were discharged to home each year (Table 2). Conclusion This longitudinal 6-year observation study of an inpatient TM ID service at a rural hospital showed remarkable annual growth in consult encounters (total growth &gt;400%). Despite increasing patient acuity, overall hospital LOS decreased over time (10.2 to 8.2 days). Patient transfers to tertiary care centers remained low (average 10.5% over 6 years) as did 30-day readmissions (average 16.3% over 6 years). The majority of patients were discharged to home (average 61.3% over 6 years). These findings show that a rural inpatient TM ID consult service can expand over time and is an effective alternative for hospitals without access to ID expertise. Disclosures John Mellors, MD, Abound Bio (Shareholder)Accelevir Diagnostics (Consultant)Co-Crystal Pharmaceuticals (Shareholder)Gilead (Consultant, Grant/Research Support)Merck (Consultant) Rima Abdel-Massih, MD, Infectious Disease Connect (Shareholder, Other Financial or Material Support, Chief Medical Officer)

scholarly journals Surgical outcome of primary intradural spinal arachnoid cysts: a series of 10 cases

2021 ◽  
Vol 57 (1) ◽  
Author(s):  
Essam Abdelhameed ◽  
Ahmed Ali Morsy
Keyword(s):  
Tertiary Care ◽  
Outer Wall ◽  
Arachnoid Cysts ◽  
Neurophysiological Monitoring ◽  
Japanese Orthopedic Association ◽  
Common Location ◽  
Before And After ◽  
Microsurgical Resection ◽  
Tertiary Care Centers ◽  
Intradural Arachnoid Cysts

Abstract Background Primary intradural spinal arachnoid cysts are rare pathologies of uncertain etiology and variable presentation from no symptoms to myelopathy or radiculopathy according to cord or root compression. MRI with diffusion and contrast differentiates them from many pathologies. There is a lot of debate regarding when to treat and how to treat such rare pathologies. Objective We present a series of 10 primary intradural arachnoid cysts and evaluate outcome after surgery. Methods This retrospective study includes patients having primary intradural spinal arachnoid cysts operated in two tertiary care centers from October 2012 till October 2019. Symptomatic cysts were subjected to microsurgical resection or outer wall excision and inner wall marsupialization under neurophysiological monitoring. The Japanese Orthopedic Association Score was used for clinical evaluation while MRI with contrast and diffusion was used for radiological evaluation before and after surgery. Results This series included 10 patients, 4 males and 6 females, with mean age of 40 years. Pain was the most common presentation. The most common location was dorsal thoracic region. Total excision was achieved in 2 cases and marsupialization in 8 cases. All symptoms improved either completely or partially after surgery. No neurological deterioration or recurrence was reported during the follow-up period in this series. Conclusion Treatment of symptomatic primary intradural spinal arachnoid cysts should be microsurgical resection, when the cyst is adherent to the cord, microscopic fenestration can be safe and effective.

scholarly journals Perception about Etiology of Epilepsy and Help-Seeking Behavior in Patients with Epilepsy

2021 ◽  
Author(s):  
Gautam Das ◽  
Samar Biswas ◽  
Souvik Dubey ◽  
Durjoy Lahiri ◽  
Biman Kanti Ray ◽  
...  
Keyword(s):  
Help Seeking ◽  
Tertiary Care ◽  
Epileptic Seizures ◽  
Treatment Seeking ◽  
Professional Help ◽  
Epileptic Patients ◽  
Seeking Behavior ◽  
Tertiary Care Centers ◽  
Patients With Epilepsy

Abstract Objectives Patients with epilepsy and their family have diverse beliefs about the cause of their illness that generally determine their treatment-seeking behavior. In this study, our aim was to find out different beliefs about epilepsy that lead to different help-seeking patterns, which act as barrier to the intended modern medical management of epilepsy. Materials and Methods One hundred and fifty consecutive consenting patients accompanied by a reliable informant/family member fulfilling the International Classification of Epileptic Seizures (ICES), simplified version, were included. Demographic and clinical data of all the eligible subjects was collected. Perceived cause of illness and help-seeking pattern were explored from patient/informant by administering proper instruments. Results Respondents identified varied causes of epilepsy and explored multiple help-seeking options before reaching tertiary care centers. We observed that, generally, epileptic patients/relatives who had belief in causes like supernatural causes sought help from nonprofessional personnel and those attributed their symptom to bodily pathology had professional help-seeking. Conclusions The belief in supernatural causes not being conformed to the biomedical models of the epileptic disorders increases the treatment gap.

scholarly journals Markers of endothelial and epithelial pulmonary injury in mechanically ventilated COVID-19 ICU patients

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Savino Spadaro ◽  
Alberto Fogagnolo ◽  
Gianluca Campo ◽  
Ottavio Zucchetti ◽  
Marco Verri ◽  
...  
Keyword(s):  
Plasma Levels ◽  
Endothelial Injury ◽  
University Hospital ◽  
Intercellular Adhesion Molecule ◽  
Secondary Outcome ◽  
Intercellular Adhesion Molecule 1 ◽  
Mechanically Ventilated ◽  
Adhesion Protein ◽  
Alveolar Epithelial ◽  
Angiopoietin 2

Abstract Background Biomarkers can be used to detect the presence of endothelial and/or alveolar epithelial injuries in case of ARDS. Angiopoietin-2 (Ang-2), soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion protein-1 (VCAM-1), P-selectin and E-selectin are biomarkers of endothelial injury, whereas the receptor for advanced glycation end-products (RAGE) reflects alveolar epithelial injury. The aims of this study were to evaluate whether the plasma concentration of the above-mentioned biomarkers was different 1) in survivors and non-survivors of COVID-19-related ARDS and 2) in COVID-19-related and classical ARDS. Methods This prospective study was performed in two COVID-19-dedicated Intensive Care Units (ICU) and one non-COVID-19 ICU at Ferrara University Hospital. A cohort of 31 mechanically ventilated patients with COVID-19 ARDS and a cohort of 11 patients with classical ARDS were enrolled. Ang-2, ICAM-1, VCAM-1, P-selectin, E-selectin and RAGE were determined with a bead-based multiplex immunoassay at three time points: inclusion in the study (T1), after 7 ± 2 days (T2) and 14 ± 2 days (T3). The primary outcome was to evaluate the plasma trend of the biomarker levels in survivors and non-survivors. The secondary outcome was to evaluate the differences in respiratory mechanics variables and gas exchanges between survivors and non-survivors. Furthermore, we compared the plasma levels of the biomarkers at T1 in patients with COVID-19-related ARDS and classical ARDS. Results In COVID-19-related ARDS, the plasma levels of Ang-2 and ICAM-1 at T1 were statistically higher in non-survivors than survivors, (p = 0.04 and p = 0.03, respectively), whereas those of P-selectin, E-selectin and RAGE did not differ. Ang-2 and ICAM-1 at T1 were predictors of mortality (AUROC 0.650 and 0.717, respectively). At T1, RAGE and P-selectin levels were higher in classical ARDS than in COVID-19-related ARDS. Ang-2, ICAM-1 and E-selectin were lower in classical ARDS than in COVID-19-related ARDS (all p < 0.001). Conclusions COVID-19 ARDS is characterized by an early pulmonary endothelial injury, as detected by Ang-2 and ICAM-1. COVID-19 ARDS and classical ARDS exhibited a different expression of biomarkers, suggesting different pathological pathways. Trial registration NCT04343053, Date of registration: April 13, 2020

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