Publications by authors named "David Seder"

Chemokines, a family of chemotactic cytokines, mediate leukocyte migration to and entrance into inflamed tissue, contributing to the intensity of local inflammation. We performed an analysis of chemokine and immune cell responses to cardiac arrest (CA). Forty-two patients resuscitated from cardiac arrest were analyzed, and twenty-two patients who underwent coronary artery bypass grafting (CABG) surgery were enrolled.

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Background: Tracheostomy in mechanically ventilated patients with severe stroke can be performed surgically or dilationally. Prospective data comparing both methods in patients with stroke are scarce. The randomized Stroke-Related Early Tracheostomy vs Prolonged Orotracheal Intubation in Neurocritical Care Trial2 (SETPOINT2) assigned 382 mechanically ventilated patients with stroke to early tracheostomy versus extubation or standard tracheostomy.

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Objective: We hypothesized that the administration of amantadine would increase awakening of comatose patients resuscitated from cardiac arrest.

Methods: We performed a prospective, randomized, controlled pilot trial, randomizing subjects to amantadine 100 mg twice daily or placebo for up to 7 days. The study drug was administered between 72 and 120 hours after resuscitation and patients with absent N20 cortical responses, early cerebral edema, or ongoing malignant electroencephalography patterns were excluded.

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Article Synopsis
  • - The management of critical care for patients post-cardiac arrest suffers from insufficient high-quality clinical studies, leading to vague guidelines and inconsistent treatment practices.
  • - Key areas like temperature control and neurological prognosis have better research backed by clinical studies, but many critical subjects lack sufficient evidence, creating gaps in guidelines.
  • - An expert panel, consisting of 24 practitioners from diverse medical fields, was convened to create consensus statements on various aspects of post-arrest management, aiming to provide guidance until more definitive studies are conducted.
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Article Synopsis
  • The management of patients post-cardiac arrest lacks strong clinical studies, leading to uncertainty and inconsistent treatment practices.
  • While some guidelines exist for critical aspects like temperature control and neurological prognosis, many important topics remain under-researched, resulting in low-quality evidence.
  • To address these gaps, an expert panel was formed to reach consensus on critical care management topics, producing statements that can help guide clinicians until higher-quality studies emerge.
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Importance: Protein binding of valproate varies among ICU patients, altering the biologically active free valproate concentration (VPAC). Free VPAC is measured at few laboratories and is often discordant with total VPAC. Existing equations to predict free VPAC are either not validated or are inaccurate in ICU patients.

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Introduction: Buprenorphine is highly effective for the treatment of opioid use disorder (OUD), and, in recent years, the rates of patients maintained on buprenorphine requiring critical care have been steadily increasing. Currently, no unified guidance exists for buprenorphine management during critical illness. Likewise, we do not know if patients maintained on buprenorphine for OUD are prescribed medications for OUD (MOUD) following hospital discharge or if buprenorphine management influences mu opioid agonist dispensing.

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Objective: SARS-CoV-2 infection has been shown to result in increased circulating levels of adenosine triphosphate and adenosine diphosphate and decreased levels of adenosine, which has important anti-inflammatory activity. The goal of this pilot project was to assess the levels of soluble CD73 and soluble Adenosine Deaminase (ADA) in hospitalized patients with COVID-19 and determine if levels of these molecules are associated with disease severity.

Methods: Plasma from 28 PCR-confirmed hospitalized COVID-19 patients who had varied disease severity based on WHO classification (6 mild/moderate, 10 severe, 12 critical) had concentrations of both soluble CD73 and ADA determined by ELISA.

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Background: The CREST model is a prediction model, quantitating the risk of circulatory-etiology death (CED) after cardiac arrest based on variables available at hospital admission, and intend to guide the triage of comatose patients without ST-segment-elevation myocardial infarction after successful cardiopulmonary resuscitation. This study assessed performance of the CREST model in the Target Temperature Management (TTM) trial cohort.

Methods: We retrospectively analyzed data from resuscitated out-of-hospital cardiac arrest (OHCA) patients in the TTM-trial.

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The number of patients maintained on buprenorphine is steadily increasing. To date, no study has reported buprenorphine management practices for these patients during critical illness, nor its relationship with supplemental full-agonist opioid administration during their hospital stay. In this single-center retrospective study, we have explored the incidence of buprenorphine continuation during critical illness among patients receiving buprenorphine for the treatment of opioid use disorder.

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Background: Cumulative research show association of neutrophils and neutrophil extracellular traps (NETs) with poor outcomes in severe COVID-19. However, to date, there is no curative intent therapy able to block neutrophil/NETs-mediated progression of multi-organ dysfunction. Because of emerging neutrophil heterogeneity, the study of subsets of circulating NET-forming neutrophils [NET + Ns] as mediators of multi-organ failure progression among patients with COVID-19 is critical to identification of therapeutic targets.

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Cumulative research show association of neutrophils and neutrophil extracellular traps (NETs) with poor outcomes in severe COVID-19. However, to date, no curative intent therapy has been identified to block neutrophil/NETs-mediated progression of multi-organ dysfunction. Because of emerging neutrophil heterogeneity, the study of subsets of circulating neutrophil-extracellular trap (NET)-forming neutrophils [NET+Ns] as mediators of multi-organ failure progression among patients with COVID-19 is critical to identification of therapeutic targets.

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Aim: Describe community consultation and surrogate consent rates for two Exception From Informed Consent (EFIC) trials for out-of-hospital cardiac arrest (OOHCA) - before and during the COVID-19 pandemic.

Methods: The PEARL study (2016-2018) randomized OOHCA patients without ST-elevation to early cardiac catheterization or not. Community consultation included flyers, radio announcements, newspaper advertisements, mailings, and in-person surveys at basketball games and ED waiting rooms.

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Unlabelled: Protein binding of valproate is variable in ICU patients, and the total valproate concentration does not predict the free valproate concentration, even when correcting for albumin. We sought to quantify valproate free concentration among ICU patients, identify risk factors associated with an increasing free valproate concentration, and evaluate the association between free valproate concentration with potential adverse drug effect.

Design: Retrospective multicenter cohort study.

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Objectives: The association between opioid therapy during critical illness and persistent opioid use after discharge is understudied relative to ICU opioid exposure and modifiable risk factors. Our objectives were to compare persistent opioid use after discharge among patients with and without chronic opioid use prior to admission (OPTA) and identify risk factors associated with persistent use.

Design: Retrospective cohort study.

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Background: Sedation and analgesia are recommended during targeted temperature management (TTM) after cardiac arrest, but there are few data to provide guidance on dosing to bedside clinicians. We evaluated differences in patient-level sedation and analgesia dosing in an international multicenter TTM trial to better characterize current practice and clinically important outcomes.

Methods: A total 950 patients in the international TTM trial were randomly assigned to a TTM of 33 °C or 36 °C after resuscitation from cardiac arrest in 36 intensive care units.

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Article Synopsis
  • Hypotension after cardiac arrest can worsen brain damage caused by lack of oxygen, and the effects of circulatory shock during hospital admission on recovery have not been thoroughly explored.
  • The study analyzed data from 4,004 adult patients who experienced out-of-hospital cardiac arrest between 2006 and 2017, focusing on the effects of low blood pressure upon admittance.
  • Findings revealed that 38% of patients were in circulatory shock upon admission, leading to a significantly lower chance of good neurological recovery, especially in those without preexisting heart conditions.
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Importance: Many patients with severe stroke have impaired airway protective reflexes, resulting in prolonged invasive mechanical ventilation.

Objective: To test whether early vs standard tracheostomy improved functional outcome among patients with stroke receiving mechanical ventilation.

Design, Setting, And Participants: In this randomized clinical trial, 382 patients with severe acute ischemic or hemorrhagic stroke receiving invasive ventilation were randomly assigned (1:1) to early tracheostomy (≤5 days of intubation) or ongoing ventilator weaning with standard tracheostomy if needed from day 10.

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We evaluated the number of CD26 expressing cells in peripheral blood of patients with COVID-19 within 72 h of admission and on day 4 and day 7 after enrollment. The majority of CD26 expressing cells were presented by CD3 CD4 lymphocytes. A low number of CD26 expressing cells were found to be associated with critical-severity COVID-19 disease.

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Background: Pneumonia is the most common infection after out-of-hospital cardiac arrest (OHCA) occurring in up to 65% of patients who remain comatose after return of spontaneous circulation. Preventing infection after OHCA may (1) reduce exposure to broad-spectrum antibiotics, (2) prevent hemodynamic derangements due to local and systemic inflammation, and (3) prevent infection-associated morbidity and mortality.

Methods: The ceftriaxone to PRevent pneumOnia and inflammaTion aftEr Cardiac arrest (PROTECT) trial is a randomized, placebo-controlled, single-center, quadruple-blind (patient, treatment team, research team, outcome assessors), non-commercial, superiority trial to be conducted at Maine Medical Center in Portland, Maine, USA.

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SARS-CoV-2 infection results in a spectrum of outcomes from no symptoms to widely varying degrees of illness to death. A better understanding of the immune response to SARS-CoV-2 infection and subsequent, often excessive, inflammation may inform treatment decisions and reveal opportunities for therapy. We studied immune cell subpopulations and their associations with clinical parameters in a cohort of 26 patients with COVID-19.

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Article Synopsis
  • The study investigates the outcomes of out-of-hospital cardiac arrest (OHCA) survivors with different rhythms, focusing on the effectiveness of coronary angiography (CAG) and percutaneous coronary intervention (PCI) in patients with nonshockable rhythms and no ST elevation (STE).
  • Data were drawn from the International Cardiac Arrest Registry (INTCAR 2.0), which includes 2113 OHCA survivors; among them, only a minority underwent CAG, yet it was found that those who did had better survival and neurological recovery rates.
  • The findings suggest that CAG should be considered even for those with nonshockable rhythms and without STE, as one in four of these patients had
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