Publications by authors named "Lance B Becker"

189 Publications

Patient Preference and Risk Assessment in Opioid Prescribing Disparities: A Secondary Analysis of a Randomized Clinical Trial.

JAMA Netw Open 2021 Jul 1;4(7):e2118801. Epub 2021 Jul 1.

Center for Emergency Care Policy and Research, University of Pennsylvania, Philadelphia.

Importance: Although racial disparities in acute pain control are well established, the role of patient analgesic preference and the factors associated with these disparities remain unclear.

Objective: To characterize racial disparities in opioid prescribing for acute pain after accounting for patient preference and to test the hypothesis that racial disparities may be mitigated by giving clinicians additional information about their patients' treatment preferences and risk of opioid misuse.

Design, Setting, And Participants: This study is a secondary analysis of data collected from Life STORRIED (Life Stories for Opioid Risk Reduction in the ED), a multicenter randomized clinical trial conducted between June 2017 and August 2019 in the emergency departments (EDs) of 4 academic medical centers. Participants included 1302 patients aged 18 to 70 years who presented to the ED with ureter colic or musculoskeletal back and/or neck pain.

Interventions: The treatment arm was randomized to receive a patient-facing intervention (not examined in this secondary analysis) and a clinician-facing intervention that consisted of a form containing information about each patient's analgesic treatment preference and risk of opioid misuse.

Main Outcomes And Measures: Concordance between patient preference for opioid-containing treatment (assessed before ED discharge) and receipt of an opioid prescription at ED discharge.

Results: Among 1302 participants in the Life STORRIED clinical trial, 1012 patients had complete demographic and treatment preference data available and were included in this secondary analysis. Of those, 563 patients (55.6%) self-identified as female, with a mean (SD) age of 40.8 (14.1) years. A total of 455 patients (45.0%) identified as White, 384 patients (37.9%) identified as Black, and 173 patients (17.1%) identified as other races. After controlling for demographic characteristics and clinical features, Black patients had lower odds than White patients of receiving a prescription for opioid medication at ED discharge (odds ratio [OR], 0.42; 95% CI, 0.27-0.65). When patients who did and did not prefer opioids were considered separately, Black patients continued to have lower odds of being discharged with a prescription for opioids compared with White patients (among those who preferred opioids: OR, 0.43 [95% CI, 0.24-0.77]; among those who did not prefer opioids: OR, 0.45 [95% CI, 0.23-0.89]). These disparities were not eliminated in the treatment arm, in which clinicians were given additional data about their patients' treatment preferences and risk of opioid misuse.

Conclusions And Relevance: In this secondary analysis of data from a randomized clinical trial, Black patients received different acute pain management than White patients after patient preference was accounted for. These disparities remained after clinicians were given additional patient-level data, suggesting that a lack of patient information may not be associated with opioid prescribing disparities.

Trial Registration: ClinicalTrials.gov Identifier: NCT03134092.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.18801DOI Listing
July 2021

Phospholipid Screening Postcardiac Arrest Detects Decreased Plasma Lysophosphatidylcholine: Supplementation as a New Therapeutic Approach.

Crit Care Med 2021 Jul 2. Epub 2021 Jul 2.

1 Laboratory for Critical Care Physiology, Feinstein Institutes for Medical Research, Manhasset, NY. 2 Department of Emergency Medicine, Northshore University Hospital, Manhasset, NY. 3 Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY. 4 Biostatistics Unit, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY.

Objectives: Cardiac arrest and subsequent resuscitation have been shown to deplete plasma phospholipids. This depletion of phospholipids in circulating plasma may contribute to organ damage postresuscitation. Our aim was to identify the diminishment of essential phospholipids in postresuscitation plasma and develop a novel therapeutic approach of supplementing these depleted phospholipids that are required to prevent organ dysfunction postcardiac arrest, which may lead to improved survival.

Design: Clinical case control study followed by translational laboratory study.

Setting: Research institution.

Patients/subjects: Adult cardiac arrest patients and male Sprague-Dawley rats.

Interventions: Resuscitated rats after 10-minute asphyxial cardiac arrest were randomized to be treated with lysophosphatidylcholine specie or vehicle.

Measurements And Main Results: We first performed a phospholipid survey on human cardiac arrest and control plasma. Using mass spectrometry analysis followed by multivariable regression analyses, we found that plasma lysophosphatidylcholine levels were an independent discriminator of cardiac arrest. We also found that decreased plasma lysophosphatidylcholine was associated with poor patient outcomes. A similar association was observed in our rat model, with significantly greater depletion of plasma lysophosphatidylcholine with increased cardiac arrest time, suggesting an association of lysophosphatidylcholine levels with injury severity. Using a 10-minute cardiac arrest rat model, we tested supplementation of depleted lysophosphatidylcholine species, lysophosphatidylcholine(18:1), and lysophosphatidylcholine(22:6), which resulted in significantly increased survival compared with control. Furthermore, the survived rats treated with these lysophosphatidylcholine species exhibited significantly improved brain function. However, supplementing lysophosphatidylcholine(18:0), which did not decrease in the plasma after 10-minute cardiac arrest, had no beneficial effect.

Conclusions: Our data suggest that decreased plasma lysophosphatidylcholine is a major contributor to mortality and brain damage postcardiac arrest, and its supplementation may be a novel therapeutic approach.
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http://dx.doi.org/10.1097/CCM.0000000000005180DOI Listing
July 2021

Pneumatosis Intestinalis in the Setting of COVID-19: A Single Center Case Series From New York.

Front Med (Lausanne) 2021 4;8:638075. Epub 2021 Jun 4.

Department of Surgery, North Shore University Hospital, Manhasset, NY, United States.

This case series reviews four critically ill patients infected with severe acute respiratory syndrome coronavirus 2 (SARSCoV2) [coronavirus disease 2019 (COVID-19)] suffering from pneumatosis intestinalis (PI) during their hospital admission. All patients received the biological agent tocilizumab (TCZ), an interleukin (IL)-6 antagonist, as an experimental treatment for COVID-19 before developing PI. COVID-19 and TCZ have been independently linked to PI risk, yet the cause of this relationship is unknown and under speculation. PI is a rare condition, defined as the presence of gas in the intestinal wall, and although its pathogenesis is poorly understood, intestinal ischemia is one of its causative agents. Based on COVID-19's association with vasculopathic and ischemic insults, and IL-6's protective role in intestinal epithelial ischemia-reperfusion injury, an adverse synergistic association of COVID-19 and TCZ can be proposed in the setting of PI. To our knowledge, this is the first published, single center, case series of pneumatosis intestinalis in COVID-19 patients who received tocilizumab therapy.
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http://dx.doi.org/10.3389/fmed.2021.638075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212022PMC
June 2021

A method for measuring the molecular ratio of inhalation to exhalation and effect of inspired oxygen levels on oxygen consumption.

Sci Rep 2021 Jun 17;11(1):12815. Epub 2021 Jun 17.

The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA.

Using a new method for measuring the molecular ratio (R) of inhalation to exhalation, we investigated the effect of high fraction of inspired oxygen (FIO2) on oxygen consumption (VO2), carbon dioxide generation (VCO2), and respiratory quotient (RQ) in mechanically ventilated rats. Twelve rats were equally assigned into two groups by anesthetics: intravenous midazolam/fentanyl vs. inhaled isoflurane. R, VO2, VCO2, and RQ were measured at FIO2 0.3 or 1.0. R error was ± 0.003. R was 1.0099 ± 0.0023 with isoflurane and 1.0074 ± 0.0018 with midazolam/fentanyl. R was 1.0081 ± 0.0017 at an FIO2 of 0.3 and 1.0092 ± 0.0029 at an FIO2 of 1.0. There were no differences in VCO2 among the groups. VO2 increased at FIO2 1.0, which was more notable when midazolam/fentanyl was used (isoflurane-FIO2 0.3: 15.4 ± 1.1; isoflurane-FIO2 1.0: 17.2 ± 1.8; midazolam/fentanyl-FIO2 0.3: 15.4 ± 1.1; midazolam/fentanyl-FIO2 1.0: 21.0 ± 2.2 mL/kg/min at STP). The RQ was lower at FIO2 1.0 than FIO2 0.3 (isoflurane-FIO2 0.3: 0.80 ± 0.07; isoflurane-FIO2 1.0: 0.71 ± 0.05; midazolam/fentanyl-FIO2 0.3: 0.79 ± 0.03; midazolam/fentanyl-FIO2 1.0: 0.59 ± 0.04). R was not affected by either anesthetics or FIO2. Inspired 100% O2 increased VO2 and decreased RQ, which might be more remarkable when midazolam/fentanyl was used.
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http://dx.doi.org/10.1038/s41598-021-91246-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211831PMC
June 2021

Pharmacological Approach for Neuroprotection After Cardiac Arrest-A Narrative Review of Current Therapies and Future Neuroprotective Cocktail.

Front Med (Lausanne) 2021 18;8:636651. Epub 2021 May 18.

Laboratory for Critical Care Physiology, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, United States.

Cardiac arrest (CA) results in global ischemia-reperfusion injury damaging tissues in the whole body. The landscape of therapeutic interventions in resuscitation medicine has evolved from focusing solely on achieving return of circulation to now exploring options to mitigate brain injury and preserve brain function after CA. CA pathology includes mitochondrial damage and endoplasmic reticulum stress response, increased generation of reactive oxygen species, neuroinflammation, and neuronal excitotoxic death. Current non-pharmacologic therapies, such as therapeutic hypothermia and extracorporeal cardiopulmonary resuscitation, have shown benefits in protecting against ischemic brain injury and improving neurological outcomes post-CA, yet their application is difficult to institute ubiquitously. The current preclinical pharmacopeia to address CA and the resulting brain injury utilizes drugs that often target singular pathways and have been difficult to translate from the bench to the clinic. Furthermore, the limited combination therapies that have been attempted have shown mixed effects in conferring neuroprotection and improving survival post-CA. The global scale of CA damage and its resultant brain injury necessitates the future of CA interventions to simultaneously target multiple pathways and alleviate the hemodynamic, mitochondrial, metabolic, oxidative, and inflammatory processes in the brain. This narrative review seeks to highlight the current field of post-CA neuroprotective pharmaceutical therapies, both singular and combination, and discuss the use of an extensive multi-drug cocktail therapy as a novel approach to treat CA-mediated dysregulation of multiple pathways, enhancing survival, and neuroprotection.
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http://dx.doi.org/10.3389/fmed.2021.636651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167895PMC
May 2021

The interplay between bystander cardiopulmonary resuscitation and ambient temperature on neurological outcome after cardiac arrest: A nationwide observational cohort study.

Resuscitation 2021 07 20;164:46-53. Epub 2021 May 20.

Laboratory for Critical Care Physiology, Feinstein Institutes for Medical Research, Northwell Health System, Manhasset, NY, USA; Department of Emergency Medicine, North Shore University Hospital, Northwell Health System, Manhasset, NY, USA; Department of Emergency Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA; Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.

Background: At lower ambient temperature, patients with out-of-hospital cardiac arrest (OHCA) easily experience hypothermia. Hypothermia has shown to improve the rate of successful return of spontaneous circulation (ROSC) in animal models. We hypothesized that lower temperature affects the impact of bystander cardiopulmonary resuscitation (CPR) on the increased odds of a favorable neurological outcome post-OHCA.

Methods: This study used information collected by the prospective, nationwide, Utstein registry to examine data from 352,689 adult patients who experienced OHCA from 2012 to 2016 in Japan. The primary outcome was a 1-month favorable neurological outcomes. Multivariable logistic regression analyses were conducted to test the impact of bystander CPR according to the temperature on the favorable outcome.

Results: A total of 201,111 patients with OHCA were included in the complete case analysis. The lower temperature group had lower proportions of receiving bystander CPR (46.5 vs. 47.9%) and having favorable outcome (2.1 vs 2.8%) than those in the higher group. Multivariable analysis revealed that bystander CPR at lower temperatures was significantly associated with favorable outcomes (adjusted odds ratio, 1.22; 95% CI, 1.09-1.37), whereas bystander CPR at higher temperatures was not associated with favorable outcomes (1.02; 0.92-1.13). The nonlinear relationship using a spline curve in the multivariable model revealed that odds ratio of favorable neurological outcomes associated with bystander CPR increased as the temperature decreased.

Conclusion: Bystander CPR was associated with favorable neurological outcomes at lower temperatures. The odds of a favorable outcome associated with bystander CPR increased as the temperature decreased.
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http://dx.doi.org/10.1016/j.resuscitation.2021.05.008DOI Listing
July 2021

Mitochondrial transplantation therapy for ischemia reperfusion injury: a systematic review of animal and human studies.

J Transl Med 2021 05 17;19(1):214. Epub 2021 May 17.

The Feinstein Institutes for Medical Research, Northwell Health System, 350 Community Drive, Manhasset, NY, USA.

Background: Mitochondria are essential organelles that provide energy for cellular functions, participate in cellular signaling and growth, and facilitate cell death. Based on their multifactorial roles, mitochondria are also critical in the progression of critical illnesses. Transplantation of mitochondria has been reported as a potential promising approach to treat critical illnesses, particularly ischemia reperfusion injury (IRI). However, a systematic review of the relevant literature has not been conducted to date. Here, we systematically reviewed the animal and human studies relevant to IRI to summarize the evidence for mitochondrial transplantation.

Methods: We searched MEDLINE, the Cochrane library, and Embase and performed a systematic review of mitochondrial transplantation for IRI in both preclinical and clinical studies. We developed a search strategy using a combination of keywords and Medical Subject Heading/Emtree terms. Studies including cell-mediated transfer of mitochondria as a transfer method were excluded. Data were extracted to a tailored template, and data synthesis was descriptive because the data were not suitable for meta-analysis.

Results: Overall, we identified 20 animal studies and two human studies. Among animal studies, 14 (70%) studies focused on either brain or heart IRI. Both autograft and allograft mitochondrial transplantation were used in 17 (85%) animal studies. The designs of the animal studies were heterogeneous in terms of the route of administration, timing of transplantation, and dosage used. Twelve (60%) studies were performed in a blinded manner. All animal studies reported that mitochondrial transplantation markedly mitigated IRI in the target tissues, but there was variation in biological biomarkers and pathological changes. The human studies were conducted with a single-arm, unblinded design, in which autologous mitochondrial transplantation was applied to pediatric patients who required extracorporeal membrane oxygenation (ECMO) for IRI-associated myocardial dysfunction after cardiac surgery.

Conclusion: The evidence gathered from our systematic review supports the potential beneficial effects of mitochondrial transplantation after IRI, but its clinical translation remains limited. Further investigations are thus required to explore the mechanisms of action and patient outcomes in critical settings after mitochondrial transplantation. Systematic review registration The study was registered at UMIN under the registration number UMIN000043347.
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http://dx.doi.org/10.1186/s12967-021-02878-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130169PMC
May 2021

Assessment of Cerebral Blood Oxygenation by Near-Infrared Spectroscopy before and after Resuscitation in a Rat Asphyxia Cardiac Arrest Model.

Adv Exp Med Biol 2021 ;1269:311-315

Feinstein Institute for Medical Research, Northwell Health System, Manhasset, NY, USA.

Clinical investigators have focused on the real-time evaluation of cerebral blood oxygenation (CBO) by near-infrared spectroscopy (NIRS) during cardiopulmonary resuscitation (CPR). A previous study showed that an abrupt increase of oxy-hemoglobin (Hb) level and tissue oxygenation index (TOI) was associated with the timing of return of spontaneous circulation (ROSC). However, it is not clear how TOI alters before and after CPR including a period of cardiac arrest (CA). Therefore, this study aimed to assess CBO with asphyxia CA and its association with CPR to ROSC in rats. Male Sprague-Dawley rats were used. We attached NIRS (NIRO-200NX, Hamamatsu Photonics, Japan) from the nasion to the upper cervical spine in rats. A ten-minute asphyxia was given to induce CA. After CA, mechanical ventilation was restarted, and manual CPR was performed. We examined the mean arterial pressure (MAP), end-tidal carbon dioxide (ETCO), and Oxy/Deoxy-Hb and TOI. Out of 14 rats, 11 obtained sustained ROSC. After the induction of asphyxia, a rapid drop of TOI was observed, followed by a subsequent increase of Oxy-Hb, Deoxy-Hb, and TOI with CPR. Recent CPR guidelines suggest the use of ETCO during CPR since its abrupt increase is a reasonable indicator of ROSC. In this study, abrupt increases in MAP, ETCO, and TOI were observed at the time of ROSC. TOI can be an alternative to ETCO for identifying ROSC after CA, and it also has the capability of monitoring CBO during and after CPR.
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http://dx.doi.org/10.1007/978-3-030-48238-1_49DOI Listing
May 2021

Effect of Adrenaline on Cerebral Blood Oxygenation Measured by NIRS in a Rat Asphyxia Cardiac Arrest Model.

Adv Exp Med Biol 2021 ;1269:277-281

Feinstein Institute for Medical Research, Northwell Health System, Manhasset, NY, USA.

Adrenaline is an important pharmacologic treatment during cardiac arrest (CA) for resuscitation. Recent studies suggest that adrenaline increases the likelihood of return of spontaneous circulation (ROSC) but does not contribute to improving neurological outcomes of CA. The mechanisms have not been elucidated yet. A bimodal increase in mean arterial pressure (MAP) is observed after adrenaline injection in rodent CA models (Okuma et al. Intensive Care Med Exp 7(1), 2019). In this study, we focused on alteration of systemic arterial pressure in conjunction with the measurement of cerebral blood oxygenation (CBO) such as oxyhemoglobin (Oxy-Hb), deoxyhemoglobin (Deoxy-Hb), and tissue oxygenation index (TOI) by near-infrared spectroscopy (NIRS). Male Sprague-Dawley rats were used. We attached NIRS between the nasion and the upper cervical spine. Rats underwent 10 minute asphyxia to induce CA. Then, cardiopulmonary resuscitation (CPR) was started, followed by a 20 μg/kg of bolus adrenaline injection at 30 seconds of CPR. This injection accelerated the first increase in MAP, and ROSC was observed with an abrupt increase in CBO. Interestingly, the second increase in MAP, once it exceeded a certain value, was accompanied by paradoxical decreases of Oxy-Hb and TOI while Deoxy-Hb increased. Based on this finding, we compared Oxy-Hb, Deoxy-Hb, and TOI at the first MAP ≈ 100 mmHg and the second MAP ≈ 100 mmHg. The average of Oxy-Hb and TOI from the 13 animals significantly decreased at the second increase in MAP over 100 mmHg while Deoxy-Hb significantly increased. NIRS identified a decrease in Oxy-Hb after ROSC. These findings may be a clue in understanding the mechanism of how and why adrenaline alters the neurological outcomes of CA post resuscitation.
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http://dx.doi.org/10.1007/978-3-030-48238-1_44DOI Listing
May 2021

Evaluation of the Quality of Chest Compression with Oxyhemoglobin Level by Near-Infrared Spectroscopy in a Rat Asphyxia Cardiac Arrest Model.

Adv Exp Med Biol 2021 ;1269:265-269

Feinstein Institute for Medical Research, Northwell Health System, Manhasset, NY, USA.

The real-time evaluation of chest compression during cardiopulmonary resuscitation is important to increase the chances of survival from a cardiac arrest (CA). In addition, cerebral oxygen level measured by near-infrared spectroscopy (NIRS) plays an important role as an indicator of return of spontaneous circulation. Recently, we developed a new method to improve the quality of chest compression using a thoracic pump in conjunction with the classic cardiac pump in a rat asphyxia CA model. This study evaluated the quality of chest compression using NIRS in male Sprague-Dawley rats. NIRS was attached between the nasion and the upper cervical spine, and rats underwent 10 minute asphyxia CA. After CA, we alternately performed three different types of chest compression (cardiac, thoracic, and cardiac plus thoracic pumps) every 30 seconds for up to 4 and a half minutes. We measured the oxyhemoglobin (Oxy-Hb), deoxyhemoglobin (Deoxy-Hb), and tissue oxygenation index (TOI) and compared these values between the groups. Oxy-Hb was significantly different among the groups (cardiac, thoracic, and cardiac plus thoracic, 1.5 ± 0.9, 4.4 ± 0.7, and 5.9 ± 2.1 μmol/L, p < 0.01, respectively), while Deoxy-Hb and TOI were not (Deoxy-HB -2.7 ± 1.2, -1.1 ± 3.2, and -1.6 ± 10.1 μmol/L; TOI, 1.8 ± 1.8, 5.5 ± 1.3, and 9.5 ± 8.0%, respectively). Oxy-Hb showed potential to evaluate the quality of chest compression in a rat asphyxia CA model.
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http://dx.doi.org/10.1007/978-3-030-48238-1_42DOI Listing
May 2021

Effect of Adrenaline on Cerebral Blood Oxygenation Measured by NIRS in a Rat Asphyxia Cardiac Arrest Model.

Adv Exp Med Biol 2021 ;1269:39-43

Feinstein Institute for Medical Research, Northwell Health System, Manhasset, NY, USA.

Adrenaline is an important pharmacologic treatment during cardiac arrest (CA) for resuscitation. Recent studies suggest that adrenaline increases the likelihood of return of spontaneous circulation (ROSC) but does not contribute to improving neurological outcomes of CA. The mechanisms have not been elucidated yet. A bimodal increase in mean arterial pressure (MAP) is observed after adrenaline injection in rodent CA models [17]. In this study, we focused on alteration of systemic arterial pressure in conjunction with the measurement of cerebral blood oxygenation (CBO) such as oxyhemoglobin (Oxy-Hb), deoxyhemoglobin (Deoxy-Hb), and tissue oxygenation index (TOI) by near-infrared spectroscopy (NIRS). Male Sprague-Dawley rats were used. We attached NIRS between the nasion and the upper cervical spine. Rats underwent 10-minute asphyxia to induce CA. Then, cardiopulmonary resuscitation (CPR) was started, followed by a 20 μg/kg of bolus adrenaline injection at 30 seconds of CPR. This injection accelerated the first increase in MAP, and ROSC was observed with an abrupt increase in CBO. Interestingly, the second increase in MAP, once it exceeded a certain value, was accompanied by paradoxical decreases of Oxy-Hb and TOI, while Deoxy-Hb increased. Based on this finding, we compared Oxy-Hb, Deoxy-Hb, and TOI at the first MAP ≈ 100 mmHg and the second MAP ≈ 100 mmHg. The average of Oxy-Hb and TOI from the 13 animals significantly decreased at the second increase in MAP over 100 mmHg, while Deoxy-Hb significantly increased. NIRS identified a decrease in Oxy-Hb after ROSC. These findings may be a clue to understanding the mechanism of how and why adrenaline alters the neurological outcomes of CA post-resuscitation.
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http://dx.doi.org/10.1007/978-3-030-48238-1_6DOI Listing
May 2021

Prospective analysis of SARS-CoV-2 dissemination to environmental surfaces during endoscopic procedures.

Endosc Int Open 2021 May 22;9(5):E701-E705. Epub 2021 Apr 22.

Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, United States.

The COVID-19 pandemic has disrupted routine medical care due to uncertainty regarding the risk of viral spread. One major concern for viral transmission to both patients and providers is performing aerosol-generating procedures such as endoscopy. As such, we performed a prospective study to examine the extent of viral contamination present in the local environment before and after endoscopic procedures on COVID-19 positive patients. A total of 82 samples were collected from 23 surfaces in the procedure area of four COVID-positive patients undergoing upper endoscopic procedures. Samples were collected both before and after the procedure. severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was extracted and quantified using reverse transcription quantitative polymerase chain reaction with primers to detect nucleocapsid RNA, and results reported as the number of viral copies per square centimeter of contaminated surface. A total of six positive samples were detected from three of the four patients. The floor beneath the patient bed was the most common site of viral RNA, but RNA was also detected on the ventilator monitor prior to the procedure and the endoscope after the procedure. The risk of SARS-CoV-2 transmission associated with upper endoscopy procedures is low based on the low rate of surface contamination. Some surfaces in close proximity to the patient and endoscopist may pose a higher risk for contamination. Patient positioning and oxygen delivery methods may influence the directionality and extent of viral spread. Our results support the use of appropriate personal protection to minimize risk of viral transmission.
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http://dx.doi.org/10.1055/a-1395-6946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062224PMC
May 2021

Methodological Issue of Mitochondrial Isolation in Acute-Injury Rat Model: Asphyxia Cardiac Arrest and Resuscitation.

Front Med (Lausanne) 2021 12;8:666735. Epub 2021 Apr 12.

The Feinstein Institutes for Medical Research at Northwell, Manhasset, NY, United States.

Identification of the mechanisms underlying mitochondrial dysfunction is key to understanding the pathophysiology of acute injuries such as cardiac arrest (CA); however, effective methods for measurement of mitochondrial function associated with mitochondrial isolation have been debated for a long time. This study aimed to evaluate the dysregulation of mitochondrial respiratory function after CA while testing the sampling bias that might be induced by the mitochondrial isolation method. Adult rats were subjected to 10-min asphyxia-induced CA. 30 min after resuscitation, the brain and kidney mitochondria from animals in sham and CA groups were isolated ( = 8, each). The mitochondrial quantity, expressed as protein concentration (isolation yields), was determined, and the oxygen consumption rates were measured. ADP-dependent (state-3) and ADP-limited (state-4) respiration activities were compared between the groups. Mitochondrial quantity was evaluated based on citrate synthase (CS) activity and cytochrome c concentration, measured independent of the isolation yields. The state-3 respiration activity and isolation yield in the CA group were significantly lower than those in the sham group (brain, < 0.01; kidney, < 0.001). The CS activity was significantly lower in the CA group as compared to that in the sham group (brain, < 0.01; kidney, < 0.01). Cytochrome c levels in the CA group showed a similar trend (brain, = 0.08; kidney, = 0.25). CA decreased mitochondrial respiration activity and the quantity of mitochondria isolated from the tissues. Owing to the nature of fragmented or damaged mitochondrial membranes caused by acute injury, there is a potential loss of disrupted mitochondria. Thus, it is plausible that the mitochondrial function in the acute-injury model may be underestimated as this loss is not considered.
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http://dx.doi.org/10.3389/fmed.2021.666735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071985PMC
April 2021

Effectiveness of SARS-CoV-2 Decontamination and Containment in a COVID-19 ICU.

Int J Environ Res Public Health 2021 03 3;18(5). Epub 2021 Mar 3.

Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, Hempstead, NY 11549, USA.

Health care systems in the United States are continuously expanding and contracting spaces to treat patients with coronavirus disease 2019 (COVID-19) in intensive care units (ICUs). As a result, hospitals must effectively decontaminate and contain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in constructed and deconstructed ICUs that care for patients with COVID-19. We assessed decontamination of a COVID-19 ICU and examined the containment efficacy of combined contact and droplet precautions in creating and maintaining a SARS-CoV-2-negative ICU "antechamber". To examine the efficacy of chemical decontamination, we used high-density, semi-quantitative environmental sampling to detect SARS-CoV-2 on surfaces in a COVID-19 ICU and COVID-19 ICU antechamber. Quantitative real-time polymerase chain reaction was used to measure viral RNA on surfaces. Viral location mapping revealed the distribution of viral RNA in the COVID-19 ICU and COVID-19 ICU antechamber. Results were further assessed using loop-mediated isothermal amplification. We collected 224 surface samples pre-decontamination and 193 samples post-decontamination from a COVID-19 ICU and adjoining COVID-19 ICU antechamber. We found that 46% of antechamber objects were positive for SARS-CoV-2 pre-decontamination despite the construction of a swinging door barrier system, implementation of contact precautions, and installation of high-efficiency particulate air filters. The object positivity rate reduced to 32.1% and viral particle rate reduced by 95.4% following decontamination. Matched items had an average of 432.2 ± 2729 viral copies/cm pre-decontamination and 19.2 ± 118 viral copies/cm post-decontamination, demonstrating significantly reduced viral surface distribution ( < 0.0001). Environmental sampling is an effective method for evaluating decontamination protocols and validating measures used to contain SARS-CoV-2 viral particles. While chemical decontamination effectively removes detectable viral RNA from surfaces, our approach to droplet/contact containment with an antechamber was not highly effective. These data suggest that hospitals should plan for the potential of aerosolized virions when creating strategies to contain SARS-CoV-2.
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http://dx.doi.org/10.3390/ijerph18052479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967612PMC
March 2021

Effects of Post-Resuscitation Normoxic Therapy on Oxygen-Sensitive Oxidative Stress in a Rat Model of Cardiac Arrest.

J Am Heart Assoc 2021 Apr 28;10(7):e018773. Epub 2021 Mar 28.

The Feinstein Institutes for Medical ResearchNorthwell Manhasset NY.

Background Cardiac arrest (CA) can induce oxidative stress after resuscitation, which causes cellular and organ damage. We hypothesized that post-resuscitation normoxic therapy would protect organs against oxidative stress and improve oxygen metabolism and survival. We tested the oxygen-sensitive reactive oxygen species from mitochondria to determine the association with hyperoxia-induced oxidative stress. Methods and Results Sprague-Dawley rats were subjected to 10-minute asphyxia-induced CA with a fraction of inspired O of 0.3 or 1.0 (normoxia versus hyperoxia, respectively) after resuscitation. The survival rate at 48 hours was higher in the normoxia group than in the hyperoxia group (77% versus 28%, <0.01), and normoxia gave a lower neurological deficit score (359±140 versus 452±85, <0.05) and wet to dry weight ratio (4.6±0.4 versus 5.6±0.5, <0.01). Oxidative stress was correlated with increased oxygen levels: normoxia resulted in a significant decrease in oxidative stress across multiple organs and lower oxygen consumption resulting in normalized respiratory quotient (0.81±0.05 versus 0.58±0.03, <0.01). After CA, mitochondrial reactive oxygen species increased by ≈2-fold under hyperoxia. Heme oxygenase expression was also oxygen-sensitive, but it was paradoxically low in the lung after CA. In contrast, the HMGB-1 (high mobility group box-1) protein was not oxygen-sensitive and was induced by CA. Conclusions Post-resuscitation normoxic therapy attenuated the oxidative stress in multiple organs and improved post-CA organ injury, oxygen metabolism, and survival. Additionally, post-CA hyperoxia increased the mitochondrial reactive oxygen species and activated the antioxidation system.
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http://dx.doi.org/10.1161/JAHA.120.018773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174361PMC
April 2021

Extracorporeal Cardiopulmonary Resuscitation in Adults. Interim Guideline Consensus Statement From the Extracorporeal Life Support Organization.

ASAIO J 2021 03;67(3):221-228

From the The Alfred Hospital, Melbourne, Australia.

Disclaimer: Veno-arterial extracorporeal membrane oxygenation (ECMO) is increasingly being deployed for selected patients in cardiac arrest who do not attain a native circulation with conventional CPR (ECPR). This ELSO guideline is intended to be a practical guide to implementing ECPR and the early management following establishment of ECMO support. Where a paucity of high-quality evidence exists, a consensus has been reached amongst the authors to provide guidance to the clinician. This guideline will be updated as further evidence in this field becomes available.
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http://dx.doi.org/10.1097/MAT.0000000000001344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984716PMC
March 2021

Inhaled Gases as Therapies for Post-Cardiac Arrest Syndrome: A Narrative Review of Recent Developments.

Front Med (Lausanne) 2020 14;7:586229. Epub 2021 Jan 14.

Laboratory for Critical Care Physiology, Feinstein Institutes for Medical Research, Northwell Health System, Manhasset, NY, United States.

Despite recent advances in the management of post-cardiac arrest syndrome (PCAS), the survival rate, without neurologic sequelae after resuscitation, remains very low. Whole-body ischemia, followed by reperfusion after cardiac arrest (CA), contributes to PCAS, for which established pharmaceutical interventions are still lacking. It has been shown that a number of different processes can ultimately lead to neuronal injury and cell death in the pathology of PCAS, including vasoconstriction, protein modification, impaired mitochondrial respiration, cell death signaling, inflammation, and excessive oxidative stress. Recently, the pathophysiological effects of inhaled gases including nitric oxide (NO), molecular hydrogen (H), and xenon (Xe) have attracted much attention. Herein, we summarize recent literature on the application of NO, H, and Xe for treating PCAS. Recent basic and clinical research has shown that these gases have cytoprotective effects against PCAS. Nevertheless, there are likely differences in the mechanisms by which these gases modulate reperfusion injury after CA. Further preclinical and clinical studies examining the combinations of standard post-CA care and inhaled gas treatment to prevent ischemia-reperfusion injury are warranted to improve outcomes in patients who are being failed by our current therapies.
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http://dx.doi.org/10.3389/fmed.2020.586229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873953PMC
January 2021

An early experience on the effect of solid organ transplant status on hospitalized COVID-19 patients.

Am J Transplant 2021 07 13;21(7):2522-2531. Epub 2021 Jan 13.

North Shore University Hospital, Northwell Health, Manhasset, New York.

We compared the outcome of COVID-19 in immunosuppressed solid organ transplant (SOT) patients to a transplant naïve population. In total, 10 356 adult hospital admissions for COVID-19 from March 1, 2020 to April 27, 2020 were analyzed. Data were collected on demographics, baseline clinical conditions, medications, immunosuppression, and COVID-19 course. Primary outcome was combined death or mechanical ventilation. We assessed the association between primary outcome and prognostic variables using bivariate and multivariate regression models. We also compared the primary endpoint in SOT patients to an age, gender, and comorbidity-matched control group. Bivariate analysis found transplant status, age, gender, race/ethnicity, body mass index, diabetes, hypertension, cardiovascular disease, COPD, and GFR <60 mL/min/1.73 m to be significant predictors of combined death or mechanical ventilation. After multivariate logistic regression analysis, SOT status had a trend toward significance (odds ratio [OR] 1.29; 95% CI 0.99-1.69, p = .06). Compared to an age, gender, and comorbidity-matched control group, SOT patients had a higher combined risk of death or mechanical ventilation (OR 1.34; 95% CI 1.03-1.74, p = .027).
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http://dx.doi.org/10.1111/ajt.16460DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206217PMC
July 2021

The evaluation of pituitary damage associated with cardiac arrest: An experimental rodent model.

Sci Rep 2021 01 12;11(1):629. Epub 2021 Jan 12.

The Feinstein Institutes for Medical Research, Northwell Health, 350 Community Dr., Manhasset, NY, 11030, USA.

The pituitary gland plays an important endocrinal role, however its damage after cardiac arrest (CA) has not been well elucidated. The aim of this study was to determine a pituitary gland damage induced by CA. Rats were subjected to 10-min asphyxia and cardiopulmonary resuscitation (CPR). Immunohistochemistry and ELISA assays were used to evaluate the pituitary damage and endocrine function. Samples were collected at pre-CA, and 30 and 120 min after cardio pulmonary resuscitation. Triphenyltetrazolium chloride (TTC) staining demonstrated the expansion of the pituitary damage over time. There was phenotypic validity between the pars distalis and nervosa. Both CT-proAVP (pars nervosa hormone) and GH/IGF-1 (pars distalis hormone) decreased over time, and a different expression pattern corresponding to the damaged areas was noted (CT-proAVP, 30.2 ± 6.2, 31.5 ± 5.9, and 16.3 ± 7.6 pg/mg protein, p < 0.01; GH/IGF-1, 2.63 ± 0.61, 0.62 ± 0.36, and 2.01 ± 0.41 ng/mg protein, p < 0.01 respectively). Similarly, the expression pattern between these hormones in the end-organ systems showed phenotypic validity. Plasma CT-proAVP (r = 0.771, p = 0.025) and IGF-1 (r = -0.775, p = 0.024) demonstrated a strong correlation with TTC staining area. Our data suggested that CA induces pathological and functional damage to the pituitary gland.
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http://dx.doi.org/10.1038/s41598-020-79780-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804952PMC
January 2021

Brain monitoring using near-infrared spectroscopy to predict outcome after cardiac arrest: a novel phenotype in a rat model of cardiac arrest.

J Intensive Care 2021 Jan 7;9(1). Epub 2021 Jan 7.

Laboratory for Critical Care Physiology, Feinstein Institutes for Medical Research, Northwell Health System, Manhasset, NY, USA.

Improving neurological outcomes after cardiac arrest (CA) is the most important patient-oriented outcome for CA research. Near-infrared spectroscopy (NIRS) enables a non-invasive, real-time measurement of regional cerebral oxygen saturation. Here, we demonstrate a novel, non-invasive measurement using NIRS, termed modified cerebral oximetry index (mCOx), to distinguish the severity of brain injury after CA. We aimed to test the feasibility of this method to predict neurological outcome after asphyxial CA in rats. Our results suggest that mCOx is feasible shortly after resuscitation and can provide a surrogate measure for the severity of brain injury in a rat asphyxia CA model.
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http://dx.doi.org/10.1186/s40560-020-00521-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787927PMC
January 2021

Advances in the Approaches Using Peripheral Perfusion for Monitoring Hemodynamic Status.

Front Med (Lausanne) 2020 7;7:614326. Epub 2020 Dec 7.

Department of Emergency Medicine, North Shore University Hospital, Northwell Health, Manhasset, NY, United States.

Measures of peripheral perfusion can be used to assess the hemodynamic status of critically ill patients. By monitoring peripheral perfusion status, clinicians can promptly initiate life-saving therapy and reduce the likelihood of shock-associated death. Historically, abnormal perfusion has been indicated by the observation of pale, cold, and clammy skin with increased capillary refill time. The utility of these assessments has been debated given that clinicians may vary in their clinical interpretation of body temperature and refill time. Considering these constraints, current sepsis bundles suggest the need to revise resuscitation guidelines. New technologies have been developed to calculate capillary refill time in the hopes of identifying a new gold standard for clinical care. These devices measure either light reflected at the surface of the fingertip (reflected light), or light transmitted through the inside of the fingertip (transmitted light). These new technologies may enable clinicians to monitor peripheral perfusion status more accurately and may increase the potential for ubiquitous hemodynamic monitoring across different clinical settings. This review will summarize the different methods available for peripheral perfusion monitoring and will discuss the advantages and disadvantages of each approach.
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http://dx.doi.org/10.3389/fmed.2020.614326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7750533PMC
December 2020

Let Sleeping Patients Lie, avoiding unnecessary overnight vitals monitoring using a clinically based deep-learning model.

NPJ Digit Med 2020 Nov 13;3(1):149. Epub 2020 Nov 13.

Institute of Bioelectronic Medicine, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA.

Impaired sleep for hospital patients is an all too common reality. Sleep disruptions due to unnecessary overnight vital sign monitoring are associated with delirium, cognitive impairment, weakened immunity, hypertension, increased stress, and mortality. It is also one of the most common complaints of hospital patients while imposing additional burdens on healthcare providers. Previous efforts to forgo overnight vital sign measurements and improve patient sleep used providers' subjective stability assessment or utilized an expanded, thus harder to retrieve, set of vitals and laboratory results to predict overnight clinical risk. Here, we present a model that incorporates past values of a small set of vital signs and predicts overnight stability for any given patient-night. Using data obtained from a multi-hospital health system between 2012 and 2019, a recurrent deep neural network was trained and evaluated using ~2.3 million admissions and 26 million vital sign assessments. The algorithm is agnostic to patient location, condition, and demographics, and relies only on sequences of five vital sign measurements, a calculated Modified Early Warning Score, and patient age. We achieved an area under the receiver operating characteristic curve of 0.966 (95% confidence interval [CI] 0.956-0.967) on the retrospective testing set, and 0.971 (95% CI 0.965-0.974) on the prospective set to predict overnight patient stability. The model enables safe avoidance of overnight monitoring for ~50% of patient-nights, while only misclassifying 2 out of 10,000 patient-nights as stable. Our approach is straightforward to deploy, only requires regularly obtained vital signs, and delivers easily actionable clinical predictions for a peaceful sleep in hospitals.
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http://dx.doi.org/10.1038/s41746-020-00355-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666176PMC
November 2020

Near-Infrared Spectroscopy Assessments of Regional Cerebral Oxygen Saturation for the Prediction of Clinical Outcomes in Patients With Cardiac Arrest: A Review of Clinical Impact, Evolution, and Future Directions.

Front Med (Lausanne) 2020 29;7:587930. Epub 2020 Oct 29.

Laboratory for Critical Care Physiology, Feinstein Institutes for Medical Research, Northwell Health System, Manhasset, NY, United States.

Despite three decades of advancements in cardiopulmonary resuscitation (CPR) methods and post-resuscitation care, neurological prognosis remains poor among survivors of out-of-hospital cardiac arrest, and there are no reliable methods for predicting neurological outcomes in patients with cardiac arrest (CA). Adopting more effective methods of neurological monitoring may aid in improving neurological outcomes and optimizing therapeutic interventions for each patient. In the present review, we summarize the development, evolution, and potential application of near-infrared spectroscopy (NIRS) in adults with CA, highlighting the clinical relevance of NIRS brain monitoring as a predictive tool in both pre-hospital and in-hospital settings. Several clinical studies have reported an association between various NIRS oximetry measurements and CA outcomes, suggesting that NIRS monitoring can be integrated into standardized CPR protocols, which may improve outcomes among patients with CA. However, no studies have established acceptable regional cerebral oxygen saturation cut-off values for differentiating patient groups based on return of spontaneous circulation status and neurological outcomes. Furthermore, the point at which resuscitation efforts can be considered futile remains to be determined. Further large-scale randomized controlled trials are required to evaluate the impact of NIRS monitoring on survival and neurological recovery following CA.
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http://dx.doi.org/10.3389/fmed.2020.587930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673454PMC
October 2020

Plasma metabolomics supports the use of long-duration cardiac arrest rodent model to study human disease by demonstrating similar metabolic alterations.

Sci Rep 2020 11 12;10(1):19707. Epub 2020 Nov 12.

Laboratory for Critical Care Physiology, Feinstein Institutes for Medical Research, 350 Community Dr, Manhasset, NY, 11030, USA.

Cardiac arrest (CA) is a leading cause of death and there is a necessity for animal models that accurately represent human injury severity. We evaluated a rat model of severe CA injury by comparing plasma metabolic alterations to human patients. Plasma was obtained from adult human control and CA patients post-resuscitation, and from male Sprague-Dawley rats at baseline and after 20 min CA followed by 30 min cardiopulmonary bypass resuscitation. An untargeted metabolomics evaluation using UPLC-QTOF-MS/MS was performed for plasma metabolome comparison. Here we show the metabolic commonality between humans and our severe injury rat model, highlighting significant metabolic dysfunction as seen by similar alterations in (1) TCA cycle metabolites, (2) tryptophan and kynurenic acid metabolites, and (3) acylcarnitine, fatty acid, and phospholipid metabolites. With substantial interspecies metabolic similarity in post-resuscitation plasma, our long duration CA rat model metabolically replicates human disease and is a suitable model for translational CA research.
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http://dx.doi.org/10.1038/s41598-020-76401-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665036PMC
November 2020

Supervised Machine Learning Applied to Automate Flash and Prolonged Capillary Refill Detection by Pulse Oximetry.

Front Physiol 2020 6;11:564589. Epub 2020 Oct 6.

Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, United States.

Objective: Develop an automated approach to detect flash (<1.0 s) or prolonged (>2.0 s) capillary refill time (CRT) that correlates with clinician judgment by applying several supervised machine learning (ML) techniques to pulse oximeter plethysmography data.

Materials And Methods: Data was collected in the Pediatric Intensive Care Unit (ICU), Cardiac ICU, Progressive Care Unit, and Operating Suites in a large academic children's hospital. Ninety-nine children and 30 adults were enrolled in testing and validation cohorts, respectively. Patients had 5 paired CRT measurements by a modified pulse oximeter device and a clinician, generating 485 waveform pairs for model training. Supervised ML models using gradient boosting (XGBoost), logistic regression (LR), and support vector machines (SVMs) were developed to detect flash (<1 s) or prolonged CRT (≥2 s) using clinician CRT assessment as the reference standard. Models were compared using Area Under the Receiver Operating Curve (AUC) and precision-recall curve (positive predictive value vs. sensitivity) analysis. The best performing model was externally validated with 90 measurement pairs from adult patients. Feature importance analysis was performed to identify key waveform characteristics.

Results: For flash CRT, XGBoost had a greater mean AUC (0.79, 95% CI 0.75-0.83) than logistic regression (0.77, 0.71-0.82) and SVM (0.72, 0.67-0.76) models. For prolonged CRT, XGBoost had a greater mean AUC (0.77, 0.72-0.82) than logistic regression (0.73, 0.68-0.78) and SVM (0.75, 0.70-0.79) models. Pairwise testing showed statistically significant improved performance comparing XGBoost and SVM; all other pairwise model comparisons did not reach statistical significance. XGBoost showed good external validation with AUC of 0.88. Feature importance analysis of XGBoost identified distinct key waveform characteristics for flash and prolonged CRT, respectively.

Conclusion: Novel application of supervised ML to pulse oximeter waveforms yielded multiple effective models to identify flash and prolonged CRT, using clinician judgment as the reference standard.

Tweet: Supervised machine learning applied to pulse oximeter waveform features predicts flash or prolonged capillary refill.
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http://dx.doi.org/10.3389/fphys.2020.564589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574820PMC
October 2020

Traumatic and hemorrhagic complications after extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest.

Resuscitation 2020 12 12;157:225-229. Epub 2020 Oct 12.

Department of Surgery, Harborview Medical Center, University of Washington, Seattle, WA, United States. Electronic address:

Introduction: Extracorporeal cardiopulmonary resuscitation (ECPR) is an emerging invasive rescue therapy for treatment of refractory out-of-hospital cardiac arrests (OHCA). We aim to describe the incidence of traumatic and hemorrhagic complications among patients undergoing ECPR for OHCA and examine the association between CPR duration and ECPR-related injuries or bleeding.

Methods: We examined prospectively collected data from the Extracorporeal Resuscitation Outcomes Database (EROD), which includes ECPR-treated OHCAs from participating hospitals (October 2014 to August 2019). The primary outcome was traumatic or hemorrhagic complications, defined any of the following: pneumothorax, pulmonary hemorrhage, major bleeding, cannula site bleeding, gastrointestinal bleeding, thoracotomy, cardiac tamponade, aortic dissection, or vascular injury during hospitalization. The primary exposure was the cardiac arrest to ECPR initiation interval (CA-ECPR interval), measured as the time from arrest to initiation of ECPR. Descriptive statistics were used to compare demographic, cardiac arrest, and ECPR characteristics among patients with and without CPR-related traumatic or bleeding complications. Multivariable logistic regression was used to examine the association between CA-ECPR interval and traumatic or bleeding complications.

Results: A total of 68 patients from 4 hospitals receiving ECPR for OHCA were entered into EROD and met inclusion criteria. Median age was 51 (interquartile range 38-58), 81% were male, 40% had body mass index > 30, and 70% had pre-existing medical comorbidities. A total of 65% had an initial shockable cardiac rhythm, mechanical CPR was utilized in at least 29% of patients, and 27% were discharged alive. The median time from arrest to ECPR initiation was 73 min (IQR 60-104). A total of 37% experienced a traumatic or bleeding complication, with major bleeding (32%), vascular injury (18%), and cannula site bleeding (15%) being the most common. Compared to patients with shorter CPR times, patients with a longer CA-ECPR interval had 18% (95% confidence interval - 2-42%) higher odds of suffering a mechanical or bleeding complication, but this did not reach statistical significance (p = 0.08).

Conclusions: Traumatic injuries and bleeding complications are common among patients undergoing ECPR. Further study is needed to investigate the relation between arrest duration and complications. Clinicians performing ECPR should anticipate and assess for injuries and bleeding in this high-risk population.
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http://dx.doi.org/10.1016/j.resuscitation.2020.09.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769956PMC
December 2020

A walk through the progression of resuscitation medicine.

Ann N Y Acad Sci 2020 Oct 10. Epub 2020 Oct 10.

Department of Emergency Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York.

Cardiac arrest (CA) is a sudden and devastating disease process resulting in more deaths in the United States than many cancers, metabolic diseases, and even car accidents. Despite such a heavy mortality burden, effective treatments have remained elusive. The past century has been productive in establishing the guidelines for resuscitation, known as cardiopulmonary resuscitation (CPR), as well as developing a scientific field whose aim is to elucidate the underlying mechanisms of CA and develop therapies to save lives. CPR has been successful in reinitiating the heart after arrest, enabling a survival rate of approximately 10% in out-of-hospital CA. Although current advanced resuscitation methods, including hypothermia and extracorporeal membrane oxygenation, have improved survival in some patients, they are unlikely to significantly improve the national survival rate any further without a paradigm shift. Such a change is possible with sustained efforts in the basic and clinical sciences of resuscitation and their implementation. This review seeks to discuss the current landscape in resuscitation medicine-how we got here and where we are going.
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http://dx.doi.org/10.1111/nyas.14507DOI Listing
October 2020

Effect of Ascorbic Acid, Corticosteroids, and Thiamine on Organ Injury in Septic Shock: The ACTS Randomized Clinical Trial.

JAMA 2020 Aug;324(7):642-650

Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

Importance: The combination of ascorbic acid, corticosteroids, and thiamine has been identified as a potential therapy for septic shock.

Objective: To determine whether the combination of ascorbic acid, corticosteroids, and thiamine attenuates organ injury in patients with septic shock.

Design, Setting, And Participants: Randomized, blinded, multicenter clinical trial of ascorbic acid, corticosteroids, and thiamine vs placebo for adult patients with septic shock. Two hundred five patients were enrolled between February 9, 2018, and October 27, 2019, at 14 centers in the United States. Follow-up continued until November 26, 2019.

Interventions: Patients were randomly assigned to receive parenteral ascorbic acid (1500 mg), hydrocortisone (50 mg), and thiamine (100 mg) every 6 hours for 4 days (n = 103) or placebo in matching volumes at the same time points (n = 102).

Main Outcomes And Measures: The primary outcome was change in the Sequential Organ Failure Assessment (SOFA) score (range, 0-24; 0 = best) between enrollment and 72 hours. Key secondary outcomes included kidney failure and 30-day mortality. Patients who received at least 1 dose of study drug were included in analyses.

Results: Among 205 randomized patients (mean age, 68 [SD, 15] years; 90 [44%] women), 200 (98%) received at least 1 dose of study drug, completed the trial, and were included in the analyses (101 with intervention and 99 with placebo group). Overall, there was no statistically significant interaction between time and treatment group with regard to SOFA score over the 72 hours after enrollment (mean SOFA score change from 9.1 to 4.4 [-4.7] points with intervention vs 9.2 to 5.1 [-4.1] points with placebo; adjusted mean difference, -0.8; 95% CI, -1.7 to 0.2; P = .12 for interaction). There was no statistically significant difference in the incidence of kidney failure (31.7% with intervention vs 27.3% with placebo; adjusted risk difference, 0.03; 95% CI, -0.1 to 0.2; P = .58) or in 30-day mortality (34.7% vs 29.3%, respectively; hazard ratio, 1.3; 95% CI, 0.8-2.2; P = .26). The most common serious adverse events were hyperglycemia (12 patients with intervention and 7 patients with placebo), hypernatremia (11 and 7 patients, respectively), and new hospital-acquired infection (13 and 12 patients, respectively).

Conclusions And Relevance: In patients with septic shock, the combination of ascorbic acid, corticosteroids, and thiamine, compared with placebo, did not result in a statistically significant reduction in SOFA score during the first 72 hours after enrollment. These data do not support routine use of this combination therapy for patients with septic shock.

Trial Registration: ClinicalTrials.gov Identifier: NCT03389555.
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http://dx.doi.org/10.1001/jama.2020.11946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7435341PMC
August 2020

Time to intra-arrest therapeutic hypothermia in out-of-hospital cardiac arrest patients and its association with neurologic outcome: a propensity matched sub-analysis of the PRINCESS trial.

Intensive Care Med 2020 Jul 8;46(7):1361-1370. Epub 2020 Jun 8.

Department of Medicine, Center for Resuscitation Science, Karolinska Institute, Solna, Sweden.

Purpose: To study the association between early initiation of intra-arrest therapeutic hypothermia and neurologic outcome in out-of-hospital cardiac arrest.

Methods: A prespecified sub-analysis of the PRINCESS trial (NCT01400373) that randomized 677 bystander-witnessed cardiac arrests to transnasal evaporative intra-arrest cooling initiated by emergency medical services or cooling started after hospital arrival. Early cooling (intervention) was defined as intra-arrest cooling initiated < 20 min from collapse (i.e., ≤ median time to cooling in PRINCESS). Propensity score matching established comparable control patients. Primary outcome was favorable neurologic outcome, Cerebral Performance Category (CPC) 1-2 at 90 days. Complete recovery (CPC 1) was among secondary outcomes.

Results: In total, 300 patients were analyzed and the proportion with CPC 1-2 at 90 days was 35/150 (23.3%) in the intervention group versus 24/150 (16%) in the control group, odds ratio (OR) 1.92, 95% confidence interval (CI) 0.95-3.85, p = .07. In patients with shockable rhythm, CPC 1-2 was 29/57 (50.9%) versus 17/57 (29.8%), OR 3.25, 95%, CI 1.06-9.97, p = .04. The proportion with CPC 1 at 90 days was 31/150 (20.7%) in the intervention group and 17/150 (11.3%) in controls, OR 2.27, 95% CI 1.12-4.62, p = .02. In patients with shockable rhythms, the proportion with CPC 1 was 27/57 (47.4%) versus 12/57 (21.1%), OR 5.33, 95% CI 1.55-18.3, p = .008.

Conclusions: In the whole study population, intra-arrest cooling initiated < 20 min from collapse compared to cooling initiated at hospital was not associated with improved favorable neurologic outcome. In the subgroup with shockable rhythms, early cooling was associated with improved favorable outcome and complete recovery.
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http://dx.doi.org/10.1007/s00134-020-06024-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7334260PMC
July 2020

Development and Validation of a Survival Calculator for Hospitalized Patients with COVID-19.

medRxiv 2020 Apr 27. Epub 2020 Apr 27.

Background: Chinese studies reported predictors of severe disease and mortality associated with coronavirus disease 2019 (COVID-19). A generalizable and simple survival calculator based on data from US patients hospitalized with COVID-19 has not yet been introduced.

Objective: Develop and validate a clinical tool to predict 7-day survival in patients hospitalized with COVID-19.

Design: Retrospective and prospective cohort study.

Setting: Thirteen acute care hospitals in the New York City area.

Participants: Adult patients hospitalized with a confirmed diagnosis of COVID-19. The development and internal validation cohort included patients hospitalized between March 1 and May 6, 2020. The external validation cohort included patients hospitalized between March 1 and May 5, 2020.

Measurements: Demographic, laboratory, clinical, and outcome data were extracted from the electronic health record. Optimal predictors and performance were identified using least absolute shrinkage and selection operator (LASSO) regression with receiver operating characteristic curves and measurements of area under the curve (AUC).

Results: The development and internal validation cohort included 11 095 patients with a median age of 65 years [interquartile range (IQR) 54-77]. Overall 7-day survival was 89%. Serum blood urea nitrogen, age, absolute neutrophil count, red cell distribution width, oxygen saturation, and serum sodium were identified as the 6 optimal of 42 possible predictors of survival. These factors constitute the NOCOS (Northwell COVID-19 Survival) Calculator. Performance in the internal validation, prospective validation, and external validation were marked by AUCs of 0.86, 0.82, and 0.82, respectively.

Limitations: All participants were hospitalized within the New York City area.

Conclusions: The NOCOS Calculator uses 6 factors routinely available at hospital admission to predict 7-day survival for patients hospitalized with COVID-19. The calculator is publicly available at https://feinstein.northwell.edu/NOCOS.
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http://dx.doi.org/10.1101/2020.04.22.20075416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7276996PMC
April 2020
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