Single-cell transcriptomics reveal a hyperacute cytokine and immune checkpoint axis after cardiac arrest in patients with poor neurological outcome

Tamura, Tomoyoshi; Cheng, Changde; Merriam, Louis T; Athar, Humra; Kim, Y.; Manandhar, Reshmi; Sheikh, Muhammad Dawood Amir; Pinilla-Vera, Mayra; Varon, Jack; Hou, Peter C.; Lawler, Patrick R.; Oldham, William M.; Seethala, Raghu R.; Tesfaigzi, Yohannes; Weissman, Alexandra; Baron, Rebecca M.; Ichinose, Fumito; Berg, Katherine M.; Bohula, Erin A.; Morrow, David A.; Chen, Xiang; Kim, Edy Y.

doi:10.1016/j.medj.2023.05.003

Cited by 4 publications

(7 citation statements)

References 105 publications

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“…Many valuable studies of OHCA acquire samples at the time of enrollment, which can be 24 h (or more) after the CA itself. Nevertheless, our companion study 1 established that time since the cardiac arrest itself (i.e., not time post-hospital presentation) is a critical variable in immunological studies of OHCA. We found that global transcriptomic shifts associated with eventual neurological outcome were apparent by 6 h post-arrest and were largely lost by 48 h post-arrest.…”

Section: Step-by-step Methods Detailsmentioning

confidence: 94%

“… 19 These findings indicate the need for deeper study into the immune mechanisms of neurological injury after CA. Towards this end, our companion study 1 created a multi-disciplinary research network to assess the immunology of peripheral blood mononuclear cells (PBMC) from OHCA patients.…”

Section: Before You Beginmentioning

confidence: 99%

“…OHCA and IHCA patients have distinct clinical characteristics and outcomes, 3 , 22 so investigators should first decide on an out-of-hospital or in-hospital focus. In our companion study, 1 we focused on OHCA to avoid the confounding effects of preexisting acute diseases, such as infections, in IHCA patients. OHCA is complicated by different confounders, such as variability in field resuscitation efforts compared to standardized in-hospital resuscitation teams.…”

Section: Before You Beginmentioning

confidence: 99%

“…In our companion study, the global transcriptomes of innate immune cells diverged between OHCA patients with good versus poor neurological outcomes as early as 6 h after OHCA. 1 …”

Section: Before You Beginmentioning

confidence: 99%

“…Following this protocol, we generated an OHCA patient biorepository and immunophenotyped cryopreserved PBMC as described in our companion study by Tamura, Cheng et al. 1 To design the clinical cohort, as described in steps 1–3, we show as an example of a case report form that captured the clinical characteristics and details of the CA, resuscitation, hospital course, and clinical endpoints according to this protocol ( File S1 ). Next, we introduce a protocol summary reviewed by our IRB (ethics board) (as in steps 4–11).…”

Section: Expected Outcomesmentioning

confidence: 99%

See 4 more Smart Citations

Protocol for immunophenotyping out-of-hospital cardiac arrest patients

Yamada,

Menon,

Kim

et al. 2024

STAR Protocols

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Section: Step-by-step Methods Detailsmentioning

confidence: 94%

Section: Before You Beginmentioning

confidence: 99%

Section: Before You Beginmentioning

confidence: 99%

“…In our companion study, the global transcriptomes of innate immune cells diverged between OHCA patients with good versus poor neurological outcomes as early as 6 h after OHCA. 1 …”

Section: Before You Beginmentioning

confidence: 99%

Section: Expected Outcomesmentioning

confidence: 99%

See 3 more Smart Citations

Protocol for immunophenotyping out-of-hospital cardiac arrest patients

Yamada,

Menon,

Kim

et al. 2024

STAR Protocols

Self Cite

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Combination of Hydrogen Inhalation and Hypothermic Temperature Control After Out-of-Hospital Cardiac Arrest: A Post hoc Analysis of the Efficacy of Inhaled Hydrogen on Neurologic Outcome Following Brain Ischemia During PostCardiac Arrest Care II Trial

Tamura,

Narumiya,

Homma

et al. 2024

Critical Care Medicine

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Objective: The Efficacy of Inhaled Hydrogen on Neurologic Outcome Following Brain Ischemia During Post-Cardiac Arrest Care (HYBRID) II trial (jRCTs031180352) suggested that hydrogen inhalation may reduce post-cardiac arrest brain injury (PCABI). However, the combination of hypothermic target temperature management (TTM) and hydrogen inhalation on outcomes is unclear. The aim of this study was to investigate the combined effect of hydrogen inhalation and hypothermic TTM on outcomes after out-of-hospital cardiac arrest (OHCA). Design: Post hoc analysis of a multicenter, randomized, controlled trial. Setting: Fifteen Japanese ICUs. Patients: Cardiogenic OHCA enrolled in the HYBRID II trial. Interventions: Hydrogen mixed oxygen (hydrogen group) versus oxygen alone (control group). Measurements and Main Results: TTM was performed at a target temperature of 32–34°C (TTM32–TTM34) or 35–36°C (TTM35–TTM36) per the institutional protocol. The association between hydrogen + TTM32–TTM34 and 90-day good neurologic outcomes was analyzed using generalized estimating equations. The 90-day survival was compared between the hydrogen and control groups under TTM32–TTM34 and TTM35–TTM36, respectively. The analysis included 72 patients (hydrogen [n = 39] and control [n = 33] groups) with outcome data. TTM32–TTM34 was implemented in 25 (64%) and 24 (73%) patients in the hydrogen and control groups, respectively (p = 0.46). Under TTM32–TTM34, 17 (68%) and 9 (38%) patients achieved good neurologic outcomes in the hydrogen and control groups, respectively (relative risk: 1.81 [95% CI, 1.05–3.66], p < 0.05). Hydrogen + TTM32–TTM34 was independently associated with good neurologic outcomes (adjusted odds ratio 16.10 [95% CI, 1.88–138.17], p = 0.01). However, hydrogen + TTM32–TTM34 did not improve survival compared with TTM32–TTM34 alone (adjusted hazard ratio: 0.22 [95% CI, 0.05–1.06], p = 0.06). Conclusions: Hydrogen + TTM32–TTM34 was associated with improved neurologic outcomes after cardiogenic OHCA compared with TTM32–TTM34 monotherapy. Hydrogen inhalation is a promising treatment option for reducing PCABI when combined with TTM32–TTM34.

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The Identification of Key Genes and Biological Pathways in Cardiac Arrest by Integrated Bioinformatics and Next Generation Sequencing Data Analysis

Vastrad,

Vastrad

2024

Preprint

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Cardiac arrest (CA) is a common cause of death world wide. The disease has lacks effective treatment. Efforts have been made to elucidate the molecular pathogenesis of CA, but the molecular mechanisms remain elusive. To identify key genes and pathways in CA, the next generation sequencing (NGS) GSE200117 dataset was downloaded from the Gene Expression Omnibus (GEO) database. DESeq2 tool was used to recognize differentially expressed genes (DEGs). Gene ontology (GO) and REACTOME pathway enrichment analyses were performed to analyze the DEGs and associated signal pathways in the g:Profiler database. The IID database was used to construct the protein-protein interaction (PPI) network, and modules analysis was performed using Cytoscape. A miRNA-hub gene regulatory network and TF-hub gene regulatory network were then constructed to screen miRNAs, TFs and hub genes by miRNet and NetworkAnalyst database and Cityscape software. Receiver operating characteristic curve (ROC) analysis used to verified the hub genes. In total, 844 DEGs were identified, comprising 414 up regulated genes and 430 down regulated genes. GO and REACTOME pathway enrichment analyses indicated that the DEGs for CA were mainly enriched in organonitrogen compound metabolic process, response to stimulus, translation and immune system. Ten hub genes (up-regulated: HSPA8, HOXA1, INCA1 and TP53; down-regulated: HSPB1, LMNA, SNCA, ADAMTSL4 and PDLIM7) were screened. We also predicted miRNAs (hsa-mir-1914-5p and hsa-mir-598-3p) and TFs (JUN and PRRX2) targeting hub genes. This study uses a series of bioinformatics technologies to obtain hug genes, miRNAs and TFs, and key pathways related to CA. These analysis results provide us with new ideas for finding biomarkers and treatment methods for CA.

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Single-cell transcriptomics reveal a hyperacute cytokine and immune checkpoint axis after cardiac arrest in patients with poor neurological outcome

Cited by 4 publications

References 105 publications

Protocol for immunophenotyping out-of-hospital cardiac arrest patients

Protocol for immunophenotyping out-of-hospital cardiac arrest patients

Combination of Hydrogen Inhalation and Hypothermic Temperature Control After Out-of-Hospital Cardiac Arrest: A Post hoc Analysis of the Efficacy of Inhaled Hydrogen on Neurologic Outcome Following Brain Ischemia During PostCardiac Arrest Care II Trial

The Identification of Key Genes and Biological Pathways in Cardiac Arrest by Integrated Bioinformatics and Next Generation Sequencing Data Analysis

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