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  1. Article ; Online: Advances in the Approaches Using Peripheral Perfusion for Monitoring Hemodynamic Status

    Julianne M. Falotico / Koichiro Shinozaki / Kota Saeki / Lance B. Becker

    Frontiers in Medicine, Vol

    2020  Volume 7

    Abstract: 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. ...

    Abstract 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.
    Keywords capillary refill time ; shock ; sepsis ; medical device ; peripheral perfusion ; optics ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2020-12-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Methodological Issue of Mitochondrial Isolation in Acute-Injury Rat Model

    Tomoaki Aoki / Yu Okuma / Lance B. Becker / Kei Hayashida / Koichiro Shinozaki

    Frontiers in Medicine, Vol

    Asphyxia Cardiac Arrest and Resuscitation

    2021  Volume 8

    Abstract: Background: 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 ... ...

    Abstract Background: 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.Materials and Methods: 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 (n = 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.Results: The state-3 respiration activity and isolation yield in the CA group were significantly lower than those in the sham group (brain, p < 0.01; kidney, p < 0.001). The CS activity was significantly lower in the CA group as compared to that in the sham group (brain, p < 0.01; kidney, p < 0.01). Cytochrome c levels in the CA group showed a similar trend (brain, p = 0.08; kidney, p = 0.25).Conclusions: 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.
    Keywords mitochondria ; mitochondrial dysfunction ; mitochondrial isolation ; oxygen consumption ; ischemic reperfusion injury ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2021-04-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Machine learning algorithms for predicting days of high incidence for out-of-hospital cardiac arrest

    Kaoru Shimada-Sammori / Tadanaga Shimada / Rie E. Miura / Rui Kawaguchi / Yasuo Yamao / Taku Oshima / Takehiko Oami / Keisuke Tomita / Koichiro Shinozaki / Taka-aki Nakada

    Scientific Reports, Vol 13, Iss 1, Pp 1-

    2023  Volume 8

    Abstract: Abstract Predicting out-of-hospital cardiac arrest (OHCA) events might improve outcomes of OHCA patients. We hypothesized that machine learning algorithms using meteorological information would predict OHCA incidences. We used the Japanese population- ... ...

    Abstract Abstract Predicting out-of-hospital cardiac arrest (OHCA) events might improve outcomes of OHCA patients. We hypothesized that machine learning algorithms using meteorological information would predict OHCA incidences. We used the Japanese population-based repository database of OHCA and weather information. The Tokyo data (2005–2012) was used as the training cohort and datasets of the top six populated prefectures (2013–2015) as the test. Eight various algorithms were evaluated to predict the high-incidence OHCA days, defined as the daily events exceeding 75% tile of our dataset, using meteorological and chronological values: temperature, humidity, air pressure, months, days, national holidays, the day before the holidays, the day after the holidays, and New Year’s holidays. Additionally, we evaluated the contribution of each feature by Shapley Additive exPlanations (SHAP) values. The training cohort included 96,597 OHCA patients. The eXtreme Gradient Boosting (XGBoost) had the highest area under the receiver operating curve (AUROC) of 0.906 (95% confidence interval; 0.868–0.944). In the test cohorts, the XGBoost algorithms also had high AUROC (0.862–0.923). The SHAP values indicated that the “mean temperature on the previous day” impacted the most on the model. Algorithms using machine learning with meteorological and chronological information could predict OHCA events accurately.
    Keywords Medicine ; R ; Science ; Q
    Subject code 006
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Monitoring the tissue perfusion during hemorrhagic shock and resuscitation

    Yusuke Endo / Taku Hirokawa / Taku Miyasho / Ryosuke Takegawa / Koichiro Shinozaki / Daniel M. Rolston / Lance B. Becker / Kei Hayashida

    Journal of Translational Medicine, Vol 19, Iss 1, Pp 1-

    tissue-to-arterial carbon dioxide partial pressure gradient in a pig model

    2021  Volume 13

    Abstract: Abstract Background Despite much evidence supporting the monitoring of the divergence of transcutaneous partial pressure of carbon dioxide (tcPCO2) from arterial partial pressure carbon dioxide (artPCO2) as an indicator of the shock status, data are ... ...

    Abstract Abstract Background Despite much evidence supporting the monitoring of the divergence of transcutaneous partial pressure of carbon dioxide (tcPCO2) from arterial partial pressure carbon dioxide (artPCO2) as an indicator of the shock status, data are limited on the relationships of the gradient between tcPCO2 and artPCO2 (tc-artPCO2) with the systemic oxygen metabolism and hemodynamic parameters. Our study aimed to test the hypothesis that tc-artPCO2 can detect inadequate tissue perfusion during hemorrhagic shock and resuscitation. Methods This prospective animal study was performed using female pigs at a university-based experimental laboratory. Progressive massive hemorrhagic shock was induced in mechanically ventilated pigs by stepwise blood withdrawal. All animals were then resuscitated by transfusing the stored blood in stages. A transcutaneous monitor was attached to their ears to measure tcPCO2. A pulmonary artery catheter (PAC) and pulse index continuous cardiac output (PiCCO) were used to monitor cardiac output (CO) and several hemodynamic parameters. The relationships of tc-artPCO2 with the study parameters and systemic oxygen delivery (DO2) were analyzed. Results Hemorrhage and blood transfusion precisely impacted hemodynamic and laboratory data as expected. The tc-artPCO2 level markedly increased as CO decreased. There were significant correlations of tc-artPCO2 with DO2 and COs (DO2: r = − 0.83, CO by PAC: r = − 0.79; CO by PiCCO: r = − 0.74; all P < 0.0001). The critical level of oxygen delivery (DO2crit) was 11.72 mL/kg/min according to transcutaneous partial pressure of oxygen (threshold of 30 mmHg). Receiver operating characteristic curve analyses revealed that the value of tc-artPCO2 for discrimination of DO2crit was highest with an area under the curve (AUC) of 0.94, followed by shock index (AUC = 0.78; P < 0.04 vs tc-artPCO2), and lactate (AUC = 0.65; P < 0.001 vs tc-artPCO2). Conclusions Our observations suggest the less-invasive tc-artPCO2 monitoring can sensitively detect inadequate systemic oxygen supply during hemorrhagic shock. Further evaluations are required in different forms of shock in other large animal models and in humans to assess its usefulness, safety, and ability to predict outcomes in critical illnesses.
    Keywords Hemorrhage ; Hemorrhagic shock ; Resuscitation ; Transcutaneous partial pressure monitoring of carbon dioxide partial pressure ; Transcutaneous partial pressure monitoring of oxygen ; Catheterization ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2021-11-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Superiority of Supervised Machine Learning on Reading Chest X-Rays in Intensive Care Units

    Kumiko Tanaka / Taka-aki Nakada / Nozomi Takahashi / Takahiro Dozono / Yuichiro Yoshimura / Hajime Yokota / Takuro Horikoshi / Toshiya Nakaguchi / Koichiro Shinozaki

    Frontiers in Medicine, Vol

    2021  Volume 8

    Abstract: Purpose: Portable chest radiographs are diagnostically indispensable in intensive care units (ICU). This study aimed to determine if the proposed machine learning technique increased in accuracy as the number of radiograph readings increased and if it ... ...

    Abstract Purpose: Portable chest radiographs are diagnostically indispensable in intensive care units (ICU). This study aimed to determine if the proposed machine learning technique increased in accuracy as the number of radiograph readings increased and if it was accurate in a clinical setting.Methods: Two independent data sets of portable chest radiographs (n = 380, a single Japanese hospital; n = 1,720, The National Institution of Health [NIH] ChestX-ray8 dataset) were analyzed. Each data set was divided training data and study data. Images were classified as atelectasis, pleural effusion, pneumonia, or no emergency. DenseNet-121, as a pre-trained deep convolutional neural network was used and ensemble learning was performed on the best-performing algorithms. Diagnostic accuracy and processing time were compared to those of ICU physicians.Results: In the single Japanese hospital data, the area under the curve (AUC) of diagnostic accuracy was 0.768. The area under the curve (AUC) of diagnostic accuracy significantly improved as the number of radiograph readings increased from 25 to 100% in the NIH data set. The AUC was higher than 0.9 for all categories toward the end of training with a large sample size. The time to complete 53 radiographs by machine learning was 70 times faster than the time taken by ICU physicians (9.66 s vs. 12 min). The diagnostic accuracy was higher by machine learning than by ICU physicians in most categories (atelectasis, AUC 0.744 vs. 0.555, P < 0.05; pleural effusion, 0.856 vs. 0.706, P < 0.01; pneumonia, 0.720 vs. 0.744, P = 0.88; no emergency, 0.751 vs. 0.698, P = 0.47).Conclusions: We developed an automatic detection system for portable chest radiographs in ICU setting; its performance was superior and quite faster than ICU physicians.
    Keywords machine learning technique ; chest radiographs ; ICU ; computer-aided detection ; deep convolutional neural network ; adaptive ensemble learning ; Medicine (General) ; R5-920
    Subject code 006
    Language English
    Publishing date 2021-10-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: The evaluation of pituitary damage associated with cardiac arrest

    Yu Okuma / Tomoaki Aoki / Santiago J. Miyara / Kei Hayashida / Mitsuaki Nishikimi / Ryosuke Takegawa / Tai Yin / Junhwan Kim / Lance B. Becker / Koichiro Shinozaki

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    An experimental rodent model

    2021  Volume 12

    Abstract: Abstract 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 ... ...

    Abstract Abstract 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.
    Keywords Medicine ; R ; Science ; Q
    Subject code 616
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: A method for measuring the molecular ratio of inhalation to exhalation and effect of inspired oxygen levels on oxygen consumption

    Koichiro Shinozaki / Yu Okuma / Kota Saeki / Santiago J. Miyara / Tomoaki Aoki / Ernesto P. Molmenti / Tai Yin / Junhwan Kim / Joshua W. Lampe / Lance B. Becker

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 13

    Abstract: Abstract 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 ( ... ...

    Abstract Abstract 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.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2021-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Inhaled Gases as Therapies for Post–Cardiac Arrest Syndrome

    Kei Hayashida / Santiago J. Miyara / Koichiro Shinozaki / Ryosuke Takegawa / Tai Yin / Daniel M. Rolston / Rishabh C. Choudhary / Sara Guevara / Ernesto P. Molmenti / Lance B. Becker

    Frontiers in Medicine, Vol

    A Narrative Review of Recent Developments

    2021  Volume 7

    Abstract: 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 ...

    Abstract 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 (H2), and xenon (Xe) have attracted much attention. Herein, we summarize recent literature on the application of NO, H2, 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.
    Keywords cardiac arrest ; cardiopulmonary resuscitation ; ischemia-reperfusion injury ; neuroprotection ; nitric oxide ; xenon ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Multi-Drug Cocktail Therapy Improves Survival and Neurological Function after Asphyxial Cardiac Arrest in Rodents

    Rishabh C. Choudhary / Muhammad Shoaib / Kei Hayashida / Tai Yin / Santiago J. Miyara / Cristina d’Abramo / William G. Heuser / Koichiro Shinozaki / Nancy Kim / Ryosuke Takegawa / Mitsuaki Nishikimi / Timmy Li / Casey Owens / Ernesto P. Molmenti / Mingzhu He / Sonya Vanpatten / Yousef Al-Abed / Junhwan Kim / Lance B. Becker

    Cells, Vol 12, Iss 1548, p

    2023  Volume 1548

    Abstract: Background: Cardiac arrest (CA) can lead to neuronal degeneration and death through various pathways, including oxidative, inflammatory, and metabolic stress. However, current neuroprotective drug therapies will typically target only one of these ... ...

    Abstract Background: Cardiac arrest (CA) can lead to neuronal degeneration and death through various pathways, including oxidative, inflammatory, and metabolic stress. However, current neuroprotective drug therapies will typically target only one of these pathways, and most single drug attempts to correct the multiple dysregulated metabolic pathways elicited following cardiac arrest have failed to demonstrate clear benefit. Many scientists have opined on the need for novel, multidimensional approaches to the multiple metabolic disturbances after cardiac arrest. In the current study, we have developed a therapeutic cocktail that includes ten drugs capable of targeting multiple pathways of ischemia–reperfusion injury after CA. We then evaluated its effectiveness in improving neurologically favorable survival through a randomized, blind, and placebo-controlled study in rats subjected to 12 min of asphyxial CA, a severe injury model. Results: 14 rats were given the cocktail and 14 received the vehicle after resuscitation. At 72 h post-resuscitation, the survival rate was 78.6% among cocktail-treated rats, which was significantly higher than the 28.6% survival rate among vehicle-treated rats (log-rank test; p = 0.006). Moreover, in cocktail-treated rats, neurological deficit scores were also improved. These survival and neurological function data suggest that our multi-drug cocktail may be a potential post-CA therapy that deserves clinical translation. Conclusions: Our findings demonstrate that, with its ability to target multiple damaging pathways, a multi-drug therapeutic cocktail offers promise both as a conceptual advance and as a specific multi-drug formulation capable of combatting neuronal degeneration and death following cardiac arrest. Clinical implementation of this therapy may improve neurologically favorable survival rates and neurological deficits in patients suffering from cardiac arrest.
    Keywords brain injury ; cell death ; cardiac arrest ; cardiopulmonary resuscitation ; cardiopulmonary bypass resuscitation ; ischemic damage ; Biology (General) ; QH301-705.5
    Subject code 610
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Timing and Location of Medical Emergency Team Activation Is Associated with Seriousness of Outcome

    Takeo Kurita / Taka-Aki Nakada / Rui Kawaguchi / Koichiro Shinozaki / Ryuzo Abe / Shigeto Oda

    PLoS ONE, Vol 11, Iss 12, p e

    An Observational Study in a Tertiary Care Hospital.

    2016  Volume 0168729

    Abstract: The medical emergency team (MET) can be activated anytime and anywhere in a hospital. We hypothesized the timing and location of MET activation are associated with seriousness of outcome.We tested for an association of clinical outcomes with timing and ... ...

    Abstract The medical emergency team (MET) can be activated anytime and anywhere in a hospital. We hypothesized the timing and location of MET activation are associated with seriousness of outcome.We tested for an association of clinical outcomes with timing and location using a university hospital cohort in Japan (n = 328). The primary outcome was short-term serious outcome (unplanned ICU admission after MET activation or death at scene).Patients for whom the MET was activated in the evening or night-time had significantly higher rates of short-term serious outcome than those for whom it was activated during the daytime (vs. evening: adjusted OR = 2. 53, 95% CI = 1.24-5.13, P = 0.010; night-time: adjusted OR = 2.45, 95% CI = 1.09-5.50, P = 0.030). Patients for whom the MET was activated in public space had decreased short-term serious outcome compared to medical spaces (public space: adjusted OR = 0.19, 95% CI = 0.07-0.54, P = 0.0017). Night-time (vs. daytime) and medical space (vs. public space) were significantly associated with higher risks of unexpected cardiac arrest and 28-day mortality.Patients for whom the MET was activated in the evening/night-time, or in medical space, had a higher rate of short-term serious outcomes. Taking measures against these risk factors may improve MET performance.
    Keywords Medicine ; R ; Science ; Q
    Subject code 150
    Language English
    Publishing date 2016-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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