Publications by authors named "Koichiro Shinozaki"

59 Publications

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

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

Near-Infrared Spectroscopy Might Help Prevent Onset of Cerebral Hyperperfusion Syndrome.

Adv Exp Med Biol 2021 ;1269:63-67

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

Cerebral hyperperfusion syndrome (CHS) is a rare but fatal perioperative complication after surgical correction of carotid stenosis. Despite numerous treatment options for preventing CHS, it does occur in some patients. We developed the outlet gate technique (OGT), in which the embolic balloon was deflated gradually in accordance with the ratio of oxygen saturation measured by a brain oximeter of the ipsilateral brain region to that in the contralateral region. Between June 2017 and May 2018, 39 patients with carotid stenosis underwent endovascular carotid revascularization procedures; of these, 20 underwent the procedure with the OGT. CBO was measured five times in those 20 patients: before the procedure, with the embolic protection device (EPD) on, with the EPD off, during the procedure, and after the procedure. Preventive treatment options were used more frequently in these patients, and although their surgical status seemed more complicated, perioperative complications were not increased. There were almost significant differences between CBO values except between those during and after the procedure with the OGT. This showed that the OGT allowed for stabilization of the CBO and thus has the potential to prevent CHS.
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http://dx.doi.org/10.1007/978-3-030-48238-1_10DOI 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

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

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

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

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

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

Shortening of low-flow duration over time was associated with improved outcomes of extracorporeal cardiopulmonary resuscitation in in-hospital cardiac arrest.

J Intensive Care 2020 15;8:39. Epub 2020 Jun 15.

Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo, Chiba, 260-8677 Japan.

Introduction: Quality improvement in the administration of extracorporeal cardiopulmonary resuscitation (ECPR) over time and its association with low-flow duration (LFD) and outcomes of cardiac arrest (CA) have been insufficiently investigated. In this study, we hypothesized that quality improvement in efforts to shorten the duration of initiating ECPR had decreased LFD over the last 15 years of experience at an academic tertiary care hospital, which in turn improved the outcomes of in-hospital CA (IHCA).

Methods: This was a single-center retrospective observational study of ECPR patients between January 2003 and December 2017. A rapid response system (RRS) and an extracorporeal membrane oxygenation (ECMO) program were initiated in 2011 and 2013. First, the association of LFD per minute with the 90-day mortality and neurological outcome was analyzed using multiple logistic regression analysis. Then, the temporal changes in LFD were investigated.

Results: Of 175 study subjects who received ECPR, 117 had IHCA. In the multivariate logistic regression, IHCA patients with shorter LFD experienced significantly increased 90-day survival and favorable neurological outcomes (LFD per minute, 90-day survival: odds ratio [OR] = 0.97, 95% confidence interval [CI] = 0.94-1.00, = 0.032; 90-day favorable neurological outcome: OR = 0.97, 95% CI = 0.94-1.00, = 0.049). In the study period, LFD significantly decreased over time (slope - 5.39 [min/3 years], < 0.0001).

Conclusion: A shorter LFD was associated with increased 90-day survival and favorable neurological outcomes of IHCA patients who received ECPR. The quality improvement in administering ECPR over time, including the RRS program and the ECMO program, appeared to ameliorate clinical outcomes.
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http://dx.doi.org/10.1186/s40560-020-00457-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294673PMC
June 2020

The standardized method and clinical experience may improve the reliability of visually assessed capillary refill time.

Am J Emerg Med 2021 06 8;44:284-290. Epub 2020 Apr 8.

The 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.

Objective: Reliability of capillary refill time (CRT) has been questionable. The purpose of this study was to examine that a standardized method and clinical experience would improve the reliability of CRT.

Methods: This was a cross-sectional study in the emergency department (ED). Health care providers (HCPs) performed CRT without instruments (method 1) to classify patients as having normal or abnormal (≤2/>2 s) CRT. An ED attending physician quantitatively measured CRT using a chronograph (standardized visual CRT, method 2). A video camera was mounted on top of the hand tool to obtain a digital recording. The videos were used to calculate CRT via image software (image CRT, method 3) as a criterion standard of methods. Additionally, 9 HCPs reviewed the videos in a separate setting in order to visually assess CRT (video CRT, method 4).

Results: We enrolled 30 patients in this study. Standardized visual CRT (method 2) identified 10 abnormal patients, while two patients were identified by CRT without instruments (method 1). There was no correlation (κ value, 0.00) between CRT without instruments (method 1) and image CRT (method 3), however the correlation between standardized visual CRT (method 2) and image CRT (method 3) was strong (r = 0.64, p < 0.01). Both intra-observer reliability and correlation coefficient with image CRT (method 3) was higher in video CRT (method 4) by more experienced clinicians.

Conclusions: Visual assessment is variable but a standardized method such as using a chronograph and/or clinical experience may aid clinicians to improve the reliability of visually assessed CRT.
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http://dx.doi.org/10.1016/j.ajem.2020.04.007DOI Listing
June 2021

Evaluation of accuracy of capillary refill index with pneumatic fingertip compression.

J Clin Monit Comput 2021 Feb 8;35(1):135-145. Epub 2020 Jan 8.

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

Capillary refill time (CRT) is a method of measuring a patient's peripheral perfusion status through a visual assessment performed by a clinician. We developed a new method of measuring CRT using standard pulse oximetry sensor, which was designated capillary refill index (CRI). We evaluated the accuracy of CRI in comparison to CRT image analysis. Thirty healthy adult volunteers were recruited for a derivation study and 30 patients in the emergency department (ED) were for validation. Our high fidelity mechanical device compresses and releases the fingertip to measure changes in blood volume using infrared-light (940 nm). CRT was calculated by image analysis software using recorded fingertip videos. CRI and CRT were measured at: room temperature (ROOM TEMP), 15 °C cold water (COLD), and 38 °C warm water (REWARM). Intra-rater reliability, Bland-Altman plots, and correlation coefficients were used to evaluate the accuracy of the novel CRI method. CRI (4.9 [95% CI 4.5-5.3] s) and CRT (4.0 [3.6-4.3]) in the COLD group were higher than the ROOM TEMP and REWARM groups. High intra-rater reliability was observed in both measurements (0.97 [0.95-0.98] and 0.98 [0.97-0.99], respectively). The Bland-Altman plots suggested a systematic bias: CRI was consistently higher than CRT (difference: + 1.01 s). There was a strong correlation between CRI and CRT (r = 0.89, p < 0.001). ED patients had higher CRI (3.91 [5.05-2.75]) and CRT (2.21 [3.19-1.23]) than those of healthy volunteers at room temperature. The same difference and correlation patterns were verified in the ED setting. CRI was as reliable as CRT by image analysis. The values of CRI was approximately 1 s higher than CRT.
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http://dx.doi.org/10.1007/s10877-019-00454-1DOI Listing
February 2021

Agreement between actual and synthesized right-sided and posterior electrocardiographic leads in identifying ischemia.

Am J Emerg Med 2020 07 18;38(7):1346-1351. Epub 2019 Nov 18.

Department of Emergency Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, United States.

Objective: A 12-lead electrocardiogram (ECG) is the standard of care for chest pain patients. However, 12-lead ECGs have difficulty detecting ischemia of the right ventricle or posterior wall of the heart. New technology exists to mathematically synthesize these leads from a 12-lead ECG; however, this technology has not been evaluated in the emergency department (ED). We assessed the level of agreement between synthesized 18-lead ECGs and actual 18-lead ECGs in identifying ST elevations, ST depressions, and T wave inversions in ED patients.

Methods: Actual 12- and 18-lead ECGs were acquired and synthesized 18-lead ECGs were produced based on waveforms from 12-lead ECGs. A blinded cardiologist interpreted the actual and synthesized 18-lead ECGs to identify the presence of abnormalities. Using actual 18-lead ECGs as the reference, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and kappa of synthesized 18-lead ECGs in identifying abnormalities were determined.

Results: Data from 295 patients were analyzed. There was 100% agreement between synthesized 18-lead ECGs and actual 18-lead ECGs in identifying ST elevations and ST depressions (sensitivity, specificity, PPV, and NPV of 100%, and kappa of 1.00). Synthesized 18-lead ECGs had 95% sensitivity, 80% specificity, 97% PPV, and 70% NPV in identifying T wave inversions, when compared with actual 18-lead ECGs (kappa: 0.70).

Conclusion: Synthesized 18-lead ECGs demonstrated 100% agreement with actual 18-lead ECGs in the identification of ST elevations and ST depressions and good agreement in the identification of T wave inversions in a sample of patients ED patients with complaints suspicious of cardiac origin.
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http://dx.doi.org/10.1016/j.ajem.2019.10.044DOI Listing
July 2020

Comparison of point-of-care peripheral perfusion assessment using pulse oximetry sensor with manual capillary refill time: clinical pilot study in the emergency department.

J Intensive Care 2019 27;7:52. Epub 2019 Nov 27.

1The Feinstein Institute for Medical Research, Northwell Health, 350 Community Dr., Manhasset, NY 11030 USA.

Background: Traditional capillary refill time (CRT) is a manual measurement that is commonly used by clinicians to identify deterioration in peripheral perfusion status. Our study compared a novel method of measuring peripheral perfusion using an investigational device with standardized visual CRT and tested the clinical usefulness of this investigational device, using an existing pulse oximetry sensor, in an emergency department (ED) setting.

Material And Methods: An ED attending physician quantitatively measured CRT using a chronometer (standardized visual CRT). The pulse oximetry sensor was attached to the same hand. Values obtained using the device are referred to as blood refill time (BRT). These techniques were compared in its numbers with the Bland-Altman plot and the predictability of patients' admissions.

Results: Thirty ED patients were recruited. Mean CRT of ED patients was 1.9 ± 0.8 s, and there was a strong correlation with BRT ( = 0.723, < 0.001). The Bland-Altman plot showed a proportional bias pattern. The ED physician identified 3 patients with abnormal CRT (> 3 s). Area under the receiver operator characteristic curve (AUC) of BRT to predict whether or not CRT was greater than 3 s was 0.82 (95% CI, 0.58-1.00). Intra-rater reliability of BRT was 0.88 (95% CI, 0.79-0.94) and that of CRT was 0.92 (0.85-0.96). Twelve patients were admitted to the hospital. AUC to predict patients' admissions was 0.67 (95% CI, 0.46-0.87) by BRT and 0.76 (0.58-0.94) by CRT.

Conclusions: BRT by a pulse oximetry sensor was an objective measurement as useful as the standardized CRT measured by the trained examiner with a chronometer at the bedside.
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http://dx.doi.org/10.1186/s40560-019-0406-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6880499PMC
November 2019

Combination of cardiac and thoracic pump theories in rodent cardiopulmonary resuscitation: a new method of three-side chest compression.

Intensive Care Med Exp 2019 Dec 2;7(1):62. Epub 2019 Dec 2.

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

Background: High-quality cardiopulmonary resuscitation (HQ-CPR) is of paramount importance to improve neurological outcomes of cardiac arrest (CA). The purpose of this study was to evaluate chest compression methods by combining two theories: cardiac and thoracic pumps.

Methods: Male Sprague-Dawley rats were used. Three types of chest compression methods were studied. The 1-side method was performed vertically with 2 fingers over the sternum. The 2-side method was performed horizontally with 2 fingers, bilaterally squeezing the chest wall. The 3-side method combined the 1-side and the 2-side methods. Rats underwent 10 min of asphyxial CA. We examined ROSC rates, the left ventricular functions, several arterial pressures, intrathoracic pressure, and brain tissue oxygen.

Results: The 3-side group achieved 100% return of spontaneous circulation (ROSC) from asphyxial CA, while the 1-side group and 2-side group achieved 80% and 60% ROSC, respectively. Three-side chest compression significantly shortened the time for ROSC among the groups (1-side, 105 ± 36.0; 2-side, 141 ± 21.7; 3-side, 57.8 ± 12.3 s, respectively, P < 0.05). Three-side significantly increased the intrathoracic pressure (esophagus, 7.6 ± 1.9, 7.3 ± 2.8, vs. 12.7 ± 2.2; mmHg, P < 0.01), the cardiac stroke volume (the ratio of the baseline 1.2 ± 0.6, 1.3 ± 0.1, vs. 2.1 ± 0.6, P < 0.05), and the common carotid arterial pressure (subtracted by femoral arterial pressure 4.0 ± 2.5, 0.3 ± 1.6, vs. 8.4 ± 2.6; mmHg, P < 0.01). Three-side significantly increased the brain tissue oxygen (the ratio of baseline 1.4±0.1, 1.3±0.2, vs. 1.6 ± 0.04, P < 0.05).

Conclusions: These results suggest that increased intrathoracic pressure by 3-side CPR improves the cardiac output, which may in turn help brain oxygenation during CPR.
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http://dx.doi.org/10.1186/s40635-019-0275-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889262PMC
December 2019

Tissue-Specific Metabolic Profiles After Prolonged Cardiac Arrest Reveal Brain Metabolome Dysfunction Predominantly After Resuscitation.

J Am Heart Assoc 2019 09 31;8(17):e012809. Epub 2019 Aug 31.

Laboratory for Critical Care Physiology Feinstein Institute for Medical Research Manhasset NY.

Background Cardiac arrest (CA) has been a leading cause of death for many decades. Despite years of research, we still do not understand how each organ responds to the reintroduction of blood flow after prolonged CA. Following changes in metabolites of individual organs after CA and resuscitation gives context to the efficiency and limitations of current resuscitation protocols. Methods and Results Adult male Sprague-Dawley rats were arbitrarily assigned into 3 groups: control, 20 minutes of CA, or 20 minutes of CA followed by 30 minutes of cardiopulmonary bypass resuscitation. The rats were euthanized by decapitation to harvest brain, heart, kidney, and liver tissues. The obtained tissue samples were analyzed by ultra-high-performance liquid chromatography-high-accuracy mass spectrometry for comprehensive metabolomics evaluation. After resuscitation, the brain showed decreased glycolysis metabolites and fatty acids and increased amino acids compared with control. Similarly, the heart displayed alterations mostly in amino acids. The kidney showed decreased amino acid and fatty acid pools with severely increased tricarboxylic acid cycle metabolites following resuscitation, while the liver showed minimal alterations with slight changes in the lipid pool. Each tissue has a distinct pattern of metabolite changes after ischemia/reperfusion. Furthermore, resuscitation worsens the metabolic dysregulation in the brain and kidney, while it normalizes metabolism in the heart. Conclusions Developing metabolic profiles using a global metabolome analysis identifies the variable nature of metabolites in individual organs after CA and reperfusion, establishing a stark contrast between the normalized heart and liver and the exacerbated brain and kidney, only after the reestablishment of blood circulation.
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http://dx.doi.org/10.1161/JAHA.119.012809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6755859PMC
September 2019

Does training level affect the accuracy of visual assessment of capillary refill time?

Crit Care 2019 05 6;23(1):157. Epub 2019 May 6.

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

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http://dx.doi.org/10.1186/s13054-019-2444-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501297PMC
May 2019

The role of decreased cardiolipin and impaired electron transport chain in brain damage due to cardiac arrest.

Neurochem Int 2018 11 1;120:200-205. Epub 2018 Sep 1.

Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA; Department of Emergency Medicine, The Feinstein Institute for Medical Research, Northwell Health System, Manhasset, NY, USA. Electronic address:

Ischemic brain damage is the major cause of mortality in cardiac arrest (CA). However, the molecular mechanism responsible for brain damage is not well understood. We previously found that mitochondrial state-3 respiration, which had been decreased following CA, was recovered in the kidney and liver, but not in the brain following cardiopulmonary bypass (CPB) resuscitation. Examination of mitochondria from these tissues may shed light on why the brain is the most vulnerable. In this study, adult male Sprague-Dawley rats were subjected to asphyxia-induced CA for 30 min or 30 min followed by 60 min CPB resuscitation. Mitochondria were then isolated from brain, heart, kidney, and liver tissues for examination using spectrophotometry and mass spectrometry to measure the activities of mitochondrial electron transport complexes and the cardiolipin content. We found significantly decreased complex I activity in mitochondria isolated from all four organs following CA, while complex III and IV activities remained intact. Following CPB resuscitation, complex I activity was normalized in kidney and liver, but unrecovered in brain and heart mitochondria. In addition, complex III activity in brain mitochondria was decreased by 22% with a concomitant decrease in cardiolipin following CPB resuscitation. These results suggest that of the tissues tested only brain mitochondria suffer reperfusion injury in addition to ischemic alterations, resulting in diminished overall mitochondrial respiration following resuscitation.
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http://dx.doi.org/10.1016/j.neuint.2018.08.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953615PMC
November 2018

Comparing phospholipid profiles of mitochondria and whole tissue: Higher PUFA content in mitochondria is driven by increased phosphatidylcholine unsaturation.

J Chromatogr B Analyt Technol Biomed Life Sci 2018 Sep 10;1093-1094:147-157. Epub 2018 Jul 10.

Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA; Department of Emergency Medicine, Feinstein Institute for Medical Research, Manhasset, NY, USA. Electronic address:

Phospholipids content in cellular and mitochondrial membranes is essential for maintaining normal function. Previous studies have found a lower polyunsaturated fatty acid (PUFA) content in mitochondria than whole tissue, theorizing decreased PUFA protects against oxidative injury. However, phospholipids (PPLs) are uniquely difficult to quantify without class separation and, as prior approaches have predominately used reverse-phase HPLC or shotgun analysis, quantitation of PPL classes may have been complicated due to the existence of numerous isobaric and isomeric species. We apply normal-phase HPLC with class separation to compare whole tissue and mitochondrial PPL profiles in rat brain, heart, kidney, and liver. In addition, we establish a novel method to ascertain PPL origin, using cardiolipin as a comparator to establish relative cardiolipin /PPL ratios. We report a higher PUFA content in tissue mitochondria driven by increased phosphatidylcholine unsaturation, suggesting mitochondria purposefully incorporate higher PUFA PPLs.
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http://dx.doi.org/10.1016/j.jchromb.2018.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7299238PMC
September 2018

Dissociated Oxygen Consumption and Carbon Dioxide Production in the Post-Cardiac Arrest Rat: A Novel Metabolic Phenotype.

J Am Heart Assoc 2018 06 29;7(13). Epub 2018 Jun 29.

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

Background: The concept that resuscitation from cardiac arrest (CA) results in a metabolic injury is broadly accepted, yet patients never receive this diagnosis. We sought to find evidence of metabolic injuries after CA by measuring O consumption and CO production (VCO) in a rodent model. In addition, we tested the effect of inspired 100% O on the metabolism.

Methods And Results: Rats were anesthetized and randomized into 3 groups: resuscitation from 10-minute asphyxia with inhaled 100% O (CA-fraction of inspired O [FIO] 1.0), with 30% O (CA-FIO 0.3), and sham with 30% O (sham-FIO 0.3). Animals were resuscitated with manual cardiopulmonary resuscitation. The volume of extracted O (VO) and VCO were measured for a 2-hour period after resuscitation. The respiratory quotient (RQ) was RQ=VCO/VO. VCO was elevated in CA-FIO 1.0 and CA-FIO 0.3 when compared with sham-FIO 0.3 in minutes 5 to 40 after resuscitation (CA-FIO 1.0: 16.7±2.2, <0.01; CA-FIO 0.3: 17.4±1.4, <0.01; versus sham-FIO 0.3: 13.6±1.1 mL/kg per minute), and then returned to normal. VO in CA-FIO 1.0 and CA-FIO 0.3 increased gradually and was significantly higher than sham-FIO 0.3 2 hours after resuscitation (CA-FIO 1.0: 28.7±6.7, <0.01; CA-FIO 0.3: 24.4±2.3, <0.01; versus sham-FIO 0.3: 15.8±2.4 mL/kg per minute). The RQ of CA animals persistently decreased (CA-FIO 1.0: 0.54±0.12 versus CA-FIO 0.3: 0.68±0.05 versus sham-FIO 0.3: 0.93±0.11, <0.01 overall).

Conclusions: CA altered cellular metabolism resulting in increased VO with normal VCO. Normal VCO suggests that the postresuscitation Krebs cycle is operating at a presumably healthy rate. Increased VO in the face of normal VCO suggests a significant alteration in O utilization in postresuscitation. Several RQ values fell well outside the normally cited range of 0.7 to 1.0. Higher FIO may increase VO, leading to even lower RQ values.
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http://dx.doi.org/10.1161/JAHA.117.007721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6064898PMC
June 2018

Novel information and communication technology system to improve surge capacity and information management in the initial hospital response to major incidents.

Am J Emerg Med 2019 02 2;37(2):351-355. Epub 2018 Jun 2.

Rinku General Medical Center, Senshu Trauma and Critical Care Center, 2-23 Rinku Orai Kita, Osaka 598-8577, Japan.

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http://dx.doi.org/10.1016/j.ajem.2018.06.007DOI Listing
February 2019

Low temperature increases capillary blood refill time following mechanical fingertip compression of healthy volunteers: prospective cohort study.

J Clin Monit Comput 2019 Apr 30;33(2):259-267. Epub 2018 May 30.

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

Capillary refill time has been accepted as a method to manually assess a patient's peripheral blood perfusion. Recently, temperature has been reported to affect capillary refill time and therefore temperature may interfere with accurate bedside peripheral blood perfusion evaluation. We applied a new method of analysis that uses standard hospital pulse oximetry equipment and measured blood refill time in order to test whether lowered fingertip temperature alters peripheral blood perfusion. Thirty adult healthy volunteers of differing races (skin colors) and age (young: 18-49 years and old: ≥ 50 years) groups were recruited. We created a high fidelity mechanical device to compress and release the fingertip and measure changes in blood volume using infrared light (940 nm). Capillary refill times were measured at the fingertip at three different temperature settings: ROOM TEMPERATURE, COLD by 15 °C cold water, and REWARM by 38 °C warm water. The COLD group has decreased fingertip temperature (23.6 ± 3.6 °C) and increased blood refill time (4.67 s [95% CI 3.57-5.76], p < 0.001). This was significantly longer than ROOM TEMPERATURE (1.96 [1.60-2.33]) and REWARM (1.96 [1.73-2.19]). Blood refill time in older subjects tended to be longer than in younger subjects (2.28 [1.61-2.94] vs. 1.65 [1.36-1.95], p = 0.077). There was a negative correlation (r = - 0.471, p = 0.009) between age and temperature. A generalized linear mixed-effects model revealed that lower temperature (OR 0.63 [95% CI 0.61-0.65], p < 0.001) rather than age (OR 1.00 [0.99-1.01], p = 0.395) was the independent factor most associated with increased blood refill time. Lowered fingertip temperatures significantly increase blood refill time which then returns to baseline when the fingertip is rewarmed. In our limited number of population, we did not find an association with age after the adjustment for the fingertip temperature.
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http://dx.doi.org/10.1007/s10877-018-0159-7DOI Listing
April 2019

Blood refill time: Clinical bedside monitoring of peripheral blood perfusion using pulse oximetry sensor and mechanical compression.

Am J Emerg Med 2018 12 5;36(12):2310-2312. Epub 2018 Apr 5.

The Feinstein Institute for Medical Research, Northwell Health System, Manhasset, NY, United States; Department of Emergency Medicine, Northshore University Hospital, Northwell Health System, Manhasset, NY, United States.

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http://dx.doi.org/10.1016/j.ajem.2018.04.006DOI Listing
December 2018
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