Post-cardiac arrest brain injury (PCABI) is the primary determinant of clinical outcomes for patients who achieve return of spontaneous circulation after cardiac arrest (CA). There are limited ...neuroprotective therapies available to mitigate the acute pathophysiology of PCABI.
Neuroprotection was one of six focus topics for the Wolf Creek XVII Conference held on June 14–17, 2023 in Ann Arbor, Michigan, USA. Conference invitees included international thought leaders and scientists in the field of CA resuscitation from academia and industry. Participants submitted via online survey knowledge gaps, barriers to translation, and research priorities for each focus topic. Expert panels used the survey results and their own perspectives and insights to create and present a preliminary unranked list for each category that was debated, revised and ranked by all attendees to identify the top 5 for each category.
Top 5 knowledge gaps included developing therapies for neuroprotection; improving understanding of the pathophysiology, mechanisms, and natural history of PCABI; deploying precision medicine approaches; optimizing resuscitation and CPR quality; and determining optimal timing for and duration of interventions. Top 5 barriers to translation included patient heterogeneity; nihilism & lack of knowledge about cardiac arrest; challenges with the translational pipeline; absence of mechanistic biomarkers; and inaccurate neuro-triage and neuroprognostication. Top 5 research priorities focused on translational research and trial optimization; addressing patient heterogeneity and individualized interventions; improving understanding of pathophysiology and mechanisms; developing mechanistic and outcome biomarkers across post-CA time course; and improving implementation of science and technology.
This overview can serve as a guide to transform the care and outcome of patients with PCABI. Addressing these topics has the potential to improve both research and clinical care in the field of neuroprotection for PCABI.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
12.
Crowned Dens Syndrome Tamura, Tomoyoshi; Suzuki, Masaru; Hori, Shingo
Internal Medicine,
01/2015, Volume:
54, Issue:
5
Journal Article
To develop a new 4/6 infarct nephrectomy (INx) model rat mimicking moderate chronic kidney disease (CKD) and to evaluate its application.
We modified the conventional 5/6 INx rat model to create the ...4/6 INx model by ligating the renal artery branch to induce infarction of one-third of the left kidney after right kidney removal and compared biochemically and histologically both models. To demonstrate the application of the 4/6 INx model, the effects of a supplementary compound containing calcium carbonate, chitosan, palm shell activated charcoal etc., that is effective for both CKD and its complications, were compared between both models.
Impairment of renal function in the 4/6 INx group was significantly more moderate than in the 5/6 INx group (P < 0.05). The 4/6 INx group showed less histological damage in kidney than in the 5/6 INx group. The supplementary compound did not improve CKD in the 5/6 INx group, but ameliorated elevation of blood urea nitrogen in the 4/6 INx group.
We developed the 4/6 INx model, which is more moderate than the conventional 5/6 INx model. This model could potentially demonstrate the effectiveness of drugs and supplements intended to prevent CKD and its progression.
Abstract Purpose: To modify a surgical catheterization method using the bent needle introducer in small animals. Methods: Eight-week-old male Lewis rats were used in the study. A needle introducer ...was created by bending a 21G injection needle at 45°. The bent needle introducer was used for catheter insertion into the left femoral artery of the rats under anesthesia. As a control, a catheter was directly inserted into the blood vessel without the introducer. The insertion time of each method was measured. Blood pressure and heart rate were measured 24 h after catheter insertion using the telemetry system. Results: Using the introducer, the catheter was successfully inserted within a short time in all rats. Without the introducer, a longer duration was required for catheter insertion. The frequency of the insertion with no catheter-based errors with the introducer tended to be higher than that without the introducer. The mean arterial pressure and heart rate 24 h after catheter insertion in each group were almost the same. Conclusions: We developed a surgical catheterization method using the introducer in small animals. This could potentially reduce the frequency of the insertion with catheter-based errors and insertion time.
Immunophenotyping of out-of-hospital cardiac arrest (OHCA) patients is of increasing interest but has challenges. Here, we describe steps for the design of the clinical cohort, planning patient ...enrollment and sample collection, and ethical review of the study protocol. We detail procedures for blood sample collection and cryopreservation of peripheral blood mononuclear cells (PBMCs). We detail steps to modulate immune checkpoints in OHCA PBMC ex vivo. This protocol also has relevance for immunophenotyping other types of critical illness.
For complete details on the use and execution of this protocol, please refer to Tamura et al. (2023).1
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•Protocol to design a clinical cardiac arrest biorepository for immunophenotyping•Steps for cryopreservation of viable peripheral blood mononuclear cells (PBMCs)•Steps for immune checkpoint modulation of cytokine production in PBMCs ex vivo•Troubleshooting a multicenter biobank of PBMC from critically ill patients
Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.
Immunophenotyping of out-of-hospital cardiac arrest (OHCA) patients is of increasing interest but has challenges. Here, we describe steps for the design of the clinical cohort, planning patient enrollment and sample collection, and ethical review of the study protocol. We detail procedures for blood sample collection and cryopreservation of peripheral blood mononuclear cells (PBMCs). We detail steps to modulate immune checkpoints in OHCA PBMC ex vivo. This protocol also has relevance for immunophenotyping other types of critical illness.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: Renal dysfunction is associated with increased cardiovascular-related mortality, but its impact on outcome of out-of-hospital cardiac arrest (OHCA) remains unclear. We assessed whether ...post-OHCA outcome correlated with renal function early after OHCA. Methods and Results: Of the 16,452 registered patients in the SOS-KANTO 2012 Study, 5,112 cardiogenic OHCA adults with creatinine measurement (mean age, 72 years; male, 64%) were examined. First-obtained creatinine was used to assess eGFR. Associations between eGFR groups, ≥60 (n=997), 45–59 (n=1,311), 30–44 (n=1,441), and <30 mL/min/1.73 m2(n=1,363), and 3-month survival and neurological outcomes were examined. Favorable neurological outcome was defined as cerebral performance categories 1 or 2. Survival rate (15.1%, 9.7%, 3.9%, and 2.9%; P<0.001) and proportion of favorable neurological outcome (12.3%, 7.4%, 2.6%, and 2.2%; P<0.001) were determined for eGFR groups ≥60, 45–59, 30–44, and <30 mL/min/1.73 m2, respectively. The survival rate decreased with eGFR (<60 mL/min/1.73 m2), and survival adjusted OR were 0.74 (95% CI: 0.54–1.03), 0.42 (95% CI: 0.28–0.62), and 0.43 (95% CI: 0.28–0.68) for eGFR 45–59, 30–44, and <30 mL/min/1.73 m2, respectively. The adjusted OR for favorable neurological outcome also decreased with eGFR: 0.74 (95% CI: 0.52–1.06), 0.40 (95% CI: 0.25–0.64), and 0.48 (95% CI: 0.29–0.81), respectively. Conclusions: An independent and graded association was observed between decreased eGFR and 3-month survival and proportion of favorable neurological outcome in cardiogenic OHCA patients.
Outcome prediction for patients with out-of-hospital cardiac arrest (OHCA) has the possibility to detect patients who could have been potentially saved. Advanced machine learning techniques have ...recently been developed and employed for clinical studies. In this study, we aimed to establish a prognostication model for OHCA with presumed cardiac aetiology using an advanced machine learning technique.
Cohort data from a prospective multi-centre cohort study for OHCA patients transported by an ambulance in the Kanto area of Japan between January 2012 and March 2013 (SOS-KANTO 2012 study) were analysed in this study. Of 16,452 patients, data for OHCA patients aged ≥18 years with presumed cardiac aetiology were retrieved, and were divided into two groups (training set: n = 5718, between January 1, 2012 and December 12, 2012; test set: n = 1608, between January 1, 2013 and March 31, 2013). Of 421 variables observed during prehospital and emergency department settings, 35 prehospital variables, or 35 prehospital and 18 in-hospital variables, were used for outcome prediction of 1-year survival using a random forest method. In validation using the test set, prognostication models trained with 35 variables, or 53 variables for 1-year survival showed area under the receiver operating characteristics curve (AUC) values of 0.943 (95% CI 0.930, 0.955) and 0.958 (95% CI 0.948, 0.969), respectively.
The advanced machine learning technique showed favourable prediction capability for 1-year survival of OHCA with presumed cardiac aetiology. These models can be useful for detecting patients who could have been potentially saved.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract only
Background:
In a randomized trial, we demonstrated that hydrogen (H
2
) inhalation improves outcomes after cardiac arrest (CA). All patients underwent target temperature management ...(TTM), but the selection of a target temperature between 32 and 36 °C varied per institutional protocol.
Hypothesis:
The combination of hypothermic TTM and H
2
improves neurological outcomes after CA.
Aims:
This study aimed to investigate the interaction of H
2
and hypothermic TTM on neurological outcomes after CA.
Methods:
This post-hoc analysis of a randomized controlled trial (HYBRID II Trial; jRCTs031180352) included comatose patients after cardiogenic out-of-hospital CA (OHCA). They received either 2% H
2
mixed oxygen (H
2
group) or oxygen alone (control group) for 18 hours under hypothermic TTM (<35°C) or normothermic TTM (35-36°C). A target temperature was reached quickly, maintained for 24 hours, and rewarmed over 48 hours. A good neurological outcome was defined as a Cerebral Performance Category (CPC) of 1 or 2 at 90 days. The neurological outcomes were compared between the H
2
and control groups under hypothermic or normothermic TTM.
Results:
The analysis included 72 patients with outcome data (39 and 33 patients in the H
2
and control group, respectively). Hypothermic TTM was implemented in 25 (64%) and 24 (73%) patients in the H
2
and control group, respectively (P=0.46). Under hypothermic TTM, 17 (68%) and 9 (38%) patients achieved CPC 1 or 2 in the H
2
and control group, respectively (relative risk 1.81 95%CI: 1.05-3.66). In contrast, under normothermic TTM, CPC of 1 or 2 was achieved in 5 (36%) and 4 (44%) patients (P>0.99) in the H
2
and control group, respectively. A multivariable logistic regression analysis indicated that the interaction between H
2
and hypothermic TTM was independently associated with CPC 1 or 2 at 90 days (adjusted odds ratio 3.71 95%CI: 1.14-12.1) after adjusting for confounding factors including age, sex, witness status, bystander CPR implementation, shockable rhythm, CA duration, and time from the return of spontaneous circulation to gas inhalation.
Conclusions:
H
2
in combination with hypothermic TTM improved neurologicaloutcomes after cardiogenic OHCA. However, the favorable effects of inhaled H
2
were not observed under normothermic TTM.
This protocol aids both new and experienced researchers in designing retrospective clinical and translational studies of acute respiratory decline in hospitalized patients. This protocol addresses ...(1) the basics of respiratory failure and electronic health record research, (2) defining patient cohorts as “mild, progressive, or severe” instead of “ICU versus non-ICU”, (3) adapting physiological indices, and (4) using biomarker trends. We apply these approaches to inflammatory biomarkers in COVID-19, but this protocol can be applied to any progressive respiratory failure study.
For complete details on the use and execution of this protocol, please refer to Mueller et al. (2020).
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•Basics of hypoxemic respiratory failure and electronic health records research•Design of patient cohorts that discriminate progressive respiratory failure•Physiological measurements of respiratory failure (P/F, ROX index)•Use of inflammatory biomarker trends to predict respiratory decline
This protocol aids both new and experienced researchers in designing retrospective clinical and translational studies of acute respiratory decline in hospitalized patients. This protocol addresses (1) the basics of respiratory failure and electronic health record research, (2) defining patient cohorts as “mild, progressive, or severe” instead of “ICU versus non-ICU”, (3) adapting physiological indices, and (4) using biomarker trends. We apply these approaches to inflammatory biomarkers in COVID-19, but this protocol can be applied to any progressive respiratory failure study.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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