Extracorporeal cardiopulmonary resuscitation as a standard of care in the future: a literature review

Vashistha Patel; Shreya Patel; Rayan Saab; Kalyan Prudhvi; Miles Cobia; Allison Rogers; Alanna Cole

doi:10.12688/f1000research.137449.1

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Review

Extracorporeal cardiopulmonary resuscitation as a standard of care in the future: a literature review

[version 1; peer review: 1 approved]

Vashistha Patel ¹, Shreya Patel¹, Rayan Saab², [...] Kalyan Prudhvi³, Miles Cobia⁴, Allison Rogers¹, Alanna Cole⁵

Vashistha Patel ¹, Shreya Patel¹, [...] Rayan Saab², Kalyan Prudhvi³, Miles Cobia⁴, Allison Rogers¹, Alanna Cole⁵

PUBLISHED 14 Sep 2023

Author details Author details

¹ Internal Medicine, Brookwood Baptist Health, Birmingham, Alabama, 35211, USA
² Interventional Cardiology, Cooperman Barnabas Medical Center, Livingston, New Jersey, 07039, USA
³ Critical Care, Princeton Baptist Medical Center, Birmingham, Alabama, 35211, USA
⁴ Neurology, Grandview Medical Center, Birmingham, Alabama, 35243, USA
⁵ Medical Library, Brookwood Baptist Health, Birmingham, Alabama, 35211, USA

Vashistha Patel
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Shreya Patel
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Rayan Saab
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Kalyan Prudhvi
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Miles Cobia
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Allison Rogers
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

Alanna Cole
Roles: Conceptualization, Data Curation, Formal Analysis, Funding Acquisition, Investigation, Methodology, Project Administration, Resources, Software, Supervision, Validation, Visualization, Writing – Original Draft Preparation, Writing – Review & Editing

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REVIEWER STATUS

This article is included in the Health Services gateway.

Abstract

Background: The use of extracorporeal cardiopulmonary resuscitation (ECPR) is limited generally to situations where traditional CPR failed to restore a patient's heart rhythm. Although ECPR is not regarded as the standard of care for cardiac arrest patients, it might be a more effective treatment for some forms of cardiac arrest. This literature review explores the efficacy of ECPR as a potential standard of care for cardiac arrest in the future.
Methods: English language publications fulfilling eligibility criteria from 2010 to 2023 were found through a literature search using four electronic databases (PubMed, Google Scholar, Cochrane, and IEEE Explore). Articles were included in this literature review for fulfilling following criteria: empirical primary studies evaluating ECPR in human subjects with either IHCA or OHCA; articles published in English between 2010 and 2023; articles exploring ECPR in cardiac arrest across all ages of patients.
Results: 12 studies out of 1,092 search results met the inclusion criteria for data extraction and synthesis. Data extracted included the efficacy of ECPR in both IHCA and OHCA patients based on the PICO framework. The quality of study done by NOS (Newcastle-Ottawa Quality Assessment Scale for Cohort Studies) resulted in three studies with moderate quality while nine were of high quality.
Conclusions: ECPR was associated with neurologically intact survival with favorable neurological outcomes compared to a standard CRP for cardiac arrest patients. This study also demonstrates that, at the moment, ECPR is the most successful in centers with a well-trained multidisciplinary ECMO team of experts. On the other hand, cardiac arrest patients in semi-rural areas and underdeveloped locations are likely to benefit less from ECPR interventions due to the lack of necessary ECPR expertise and infrastructure. Those individuals eligible for ECPR benefit from better neurological outcomes and associated higher survival rates.

Keywords

extracorporeal cardiopulmonary resuscitation, ECPR, extracorporeal life support, ECMO, out-of-hospital cardiac arrest, in-hospital cardiac arrest

Corresponding author: Vashistha Patel

Competing interests: No competing interests were disclosed.

Grant information: The author(s) declared that no grants were involved in supporting this work.

Copyright: © 2023 Patel V et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

How to cite: Patel V, Patel S, Saab R et al. Extracorporeal cardiopulmonary resuscitation as a standard of care in the future: a literature review [version 1; peer review: 1 approved]. F1000Research 2023, 12:1149 (https://doi.org/10.12688/f1000research.137449.1) First published: 14 Sep 2023, 12:1149 (https://doi.org/10.12688/f1000research.137449.1) Latest published: 14 Sep 2023, 12:1149 (https://doi.org/10.12688/f1000research.137449.1)

Introduction

Cardiac arrest (CA) is one of the leading causes of death worldwide.¹^,² CA prevalence accounts for nearly 350,000 cases in the US,³ and whether out-of-hospital (OHCA)⁴^–⁶ or in-hospital CA (IHCA),⁷^,⁸ cardiac arrest is responsible for the morality of more than half a million individuals every year worldwide.⁹^,¹⁰ Although adult CA survival rates have increased over the past 20 years, only just 22% of IHCA patients and less than 10% of OHCA patients survive.¹¹^,¹² Notably, less than 10% of survivors have satisfactory neurological outcomes when discharged from hospitals despite standardizing basic cardiac resuscitation, post-arrest care, and application with personalized therapies.³^,¹³ Extracorporeal cardiopulmonary resuscitation (ECPR) is a potentially life-saving therapy for patients in cardiac arrest who otherwise are unresponsive to traditional cardiopulmonary resuscitation (CPR).¹⁴^,¹⁵ ECPR involves cardiopulmonary bypass maintaining circulation and perfusion to vital organs while¹⁶ the patient’s body recovers from the underlying condition that caused the cardiac arrest.¹⁷^–¹⁹

Currently, ECPR is not considered a standard of care for cardiac arrest patients,²⁰ and it is typically reserved for cases where conventional CPR has failed to restore a patient’s heart rhythm.²¹^,²² There is growing evidence to suggest that ECPR may be a more effective treatment for certain types of cardiac arrest,²³ particularly those caused by conditions such as pulmonary embolism, hypothermia, or drug overdose.²⁴ As a result, some healthcare systems consider ECPR as an essential standard of care for cardiac arrest patients.²⁵ For instance, in some parts of the world, emergency medical services have implemented ECPR programs that allow trained responders to perform the procedure on eligible patients in the field.²⁶^–²⁸ While use of ECPR as a standard of care for cardiac arrest is still the subject of ongoing research, it is clear that this therapy has potential to save many lives. In this regard, our literature review aims to explore the efficacy of ECPR as a potential standard of care for cardiac arrest patients in the future.

Methods

Study design and sources

We adhered to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) standards to prepare this literature review.²⁹ Bibliographic searches were conducted using four electronic databases: PubMed, Google Scholar, Cochrane, and IEEE Explore.

Search criteria

Using a set of keywords, computerized bibliographic searches were carried out in PubMed, Google Scholar, Cochrane, and IEEE Explore. The search was limited to English language articles dating from 2010 to 2023. We utilized the following search terms: (“extracorporeal cardiopulmonary resuscitation” OR “ECPR” OR “extracorporeal oxygenation” OR “extracorporeal life support” OR “percutaneous cardiopulmonary support” OR “ECMO” OR “extracorporeal circulation”) AND (“cardiopulmonary resuscitation” OR “CPR” OR “conventional CPR” OR “CCPR”) AND (“out-of-hospital cardiac arrest” OR “in-hospital cardiac arrest” OR “cardiac arrest” OR “heart arrest” OR “OHCA” OR “IHCA”).

Eligibility criteria

Articles were included in this literature review for fulfilling following criteria:

• Empirical primary studies evaluating ECPR in human subjects with either IHCA or OHCA.
• Articles published in English between 2010 and 2023.
• Articles exploring ECPR in cardiac arrest across all ages of patients.

Studies were eliminated based on the following exclusion criteria:

• Secondary sources including other reviews, newspaper articles, magazines, conference proceedings, and unpublished data sets.
• Non-English language studies.
• Studies older than 2010.

Data extraction

Each eligible publication’s study characteristics and data were extracted by us in adherence to the PICO framework.³⁰ These characteristics and data included the first author’s name, the publication year, the country of origin, the study’s design, the location of the arrest (OHCA or IHCA), the number of patients, the sex ratio, and the mean age.

Data syntheses and quality evaluation

Authors pooled the findings from the included articles, and the results of all the research under consideration were then available for synthesis and analysis. A modified version of the Newcastle-Ottawa Quality Assessment Scale for Cohort Studies was used to rate effectiveness of each study (NOS)³¹ (Table 1).

Table 1. Shows the Newcastle-Ottawa Quality Assessment Scale assessing the quality of the collected studies.

Study	Selection (Maximum 5 points)	Comparability (Maximum 2 points)	Outcome (Maximum 3 points)	Total score	Quality
Bartos et al., 2020³²	4	2	2	8	High
Chandru et al., 2021³³	3	1	1	5	Medium
Djordjevic et al.,2021³⁴	4	1	1	6	Medium
Iwashita et al., 2020³⁵	5	1	2	8	High
Kim et al., 2014³⁶	3	2	3	8	High
Nee et al., 2020³⁷	3	2	1	6	Medium
Patricio et al., 2019³⁸	3	2	2	7	High
Poppe et al., 2020³⁹	4	1	3	8	High
Read et al. 2022⁴⁰	4	2	1	7	High
Schober et al., 2017⁴¹	3	2	2	7	High
ter Avest et al., 2022⁴²	3	2	3	8	High
Yu et al., 2018⁴³	4	1	1	6	Medium

Results and discussion

Search results

A total of 1,092 pertinent articles were found in the literature search across four electronic databases. The authors eliminated 373 duplicate articles. The remaining articles’ titles and abstracts were scrutinized for the research subject and 338 were excluded as these studies did not meet the research criteria. The remaining 381 articles were reduced to 140 after the inability to retrieve 241, and the remaining 140 were evaluated based on the predetermined eligibility standards. Eventually, only 12 articles met the requirements after being evaluated using the qualifying criteria (Tabulated in study characteristics in Table 2 and Table 3). The other 140 papers were disregarded on the grounds that 26 were published before 2010, 38 were non-English articles, 39 were abstracts and 25 were systematic reviews, letters to the editor, case reports, and magazines. The study selection process is shown in Figure 1.

Table 2. Bibliographic details and Patient characteristics of the12 articles included after qualifying criteria.

Author, year	Setting, nation	Sample size (N)	Type of CA	Sex (Male/Female)	Mean age (years)
Bartos et al., 2020³²	University of Minnesota, US	160 consecutive VF/VT adult patients and 654 adults in the ALPS trial	OHCA	ECPR - 126/34 ALPS - 528/126	ECPR - 57 ± 1.0 ALPS - 59 ± 0.4
Chandru et al. 2021³³	Western Sydney Local Health District, Australia	248 eligible CA comprised 89 VF, 9 VT, 85 PEA, and 57 Asystole. Bystander CPR = 175	OHCA	161/87	64 (IQR = 53-75)
Djordjevic et al.,2021³⁴	University Hospital Cologne, Germany	44 patients	OHCA	40/4	53 ± 12
Iwashita et al., 2020³⁵	Auckland City Hospital, New Zealand	328 patients	IHCA	97/53	63.6 ± 16
Kim et al., 2014³⁶	Korea University Medical Center, Korea	ECPR = 55 CCPR = 444	OHCA	ECPR - 40/2 CCPR - 285/159	EPCR - 53 (41–68) CCPR - 69 (56–77)
Nee et al., 2020³⁷	Charité Berlin, Germany	254 consecutive patients	OHCA	175/49	54 (43–64)
Patricio et al., 2019³⁸	Erasme University Hospital, Brussels, Belgium	ECPR = 112 CCPR = 80	IHCA/OHCA	ECPR - 83/29 CCPR - 336/523	CCPR - 65 ± 16 ECPR - 54 ± 16
Poppe et al., 2020³⁹	Vienna, Austria	92 patients	IHCA/OHCA	72/20	48 (14)
Read et al., 2022⁴⁰	St Vincent's Hospital, Sydney, Australia	Pre-intervention = 27 Pos-intervention = 39	IHCA/OHCA	Pre - 17/10 Post - 28/11	Pre - 51 (3) Post - 55 (3)
Schober et al., 2017⁴¹	Medical University of Vienna, Austria	239 patients	OHCA	ECPR = 5/2 CCPR = 173/59	ECPR - 46 (31–59) CCPR - 60 (50–70)
ter Avest et al., 2022⁴²	Kings College, UK	162 patients	IHCA/OHCA	n/s	<60
Yu et al., 2018⁴³	Taiwan University Hospital	482 patients	IHCA/OHCA	368/114	49.4 ± 11.8

Table 3. Study design, objectives, interventions, outcomes, and results with neurological outcomes.

Study	Study design	Study objectives	Intervention	Comparator	Evaluated outcome measures	Results
Bartos et al., 2020³²	RS	To investigate the impact of resuscitation time on patient survival and metabolic profile during ECPR for VF/VT OHCA	ECPR	ALPS-CPR	The survival rate, resuscitation duration, and metabolic changes.	Neurologically favorable survival in ECPR than in ALPS patients (33% versus 23%; P = 0.01) with a longer mean duration (60 minutes versus 35 minutes; P < 0.001)
Chandru et al., 2021³³	OS	To predict the likely future caseload of ECMO at historically "low volume" centers.	ECPR	Bystander CPR	ROSC rates and survival rates.	Survival for VF, VT, PEA, and asystole was 43, 33, 9.4, and 8.7%, respectively. ROSC rates for VF, VT, PEA, and asystole were 64, 66, 55.3, and 42.1%, respectively.
Djordjevic et al.,2021³⁴	RS	ECPR outcomes and risk factors for OHC	ECPR	n/s	Survival and risk factors	10 (23%) patients discharged and shorter pre-hospital CPR duration (60 (59;60) min (S) vs. 60 (55;90) min (NS), p = 0.07)
Iwashita et al., 2020³⁵	RS	ECPR for advanced cardiac support	ECPR	n/s	Survival and ECPR-eligibility	Seven (10.8%) were eligible, and one survivor
Kim et al., 2014³⁶	RS	To identify indicators predicting good neurologic outcomes, determine the ideal CPR duration to initiate ECPR as an alternate.	ECPR	CCPR	The optimal duration and predicting neurologic outcome.	CPR of <21 minutes is recommended for a satisfactory neurologic result.
Nee et al., 2020³⁷	PCS	ECPR efficacy	ECPR	n/s	ROSC and survival	Survivors¹⁸ had considerably less acidosis (pH 7.2 (IQR 7.15-7.4) vs. 7.0), and shorter times between collapse and the beginning of ECPR (58 min (IQR 12-85) vs. 90 min (IQR 74-114).
Patricio et al., 2019³⁸	RS	To compare ECPR and CCPR for patients with refractory CA	ECPR	CCPR	ROSC, ECMO, survival, and death	The ROSC rate = 54 min and 22 sec (77/80, 96%) and 54 min and 19 sec (30/80, 38%) for CCPR. the survival rate to ICU discharge was ECPR 18/80 (23%) vs. CCPR 14/80 (18%) (p = 0.42).
Poppe et al., 2020³⁹	RS	Validation of ECPR criteria	ECPR	n/s	ECPR eligibility, six criteria checklists.	Twenty-seven patients met all criteria and had 30-day survival noticeably higher [OR 6.0 (95% CI 1.78 to 20.19)]. P ¼ 0.004
Read et al. 2022⁴⁰	RS	Evaluating the relationship between ECPR use, ROSC, and neurologically stable survival	ECPR	n/s	CPC, ROSC, survival, and time to ECMO	OHCA to ECMO decreased from 87 (IQR 78-95) to 70 (IQR 69-72) minutes post-intervention (p = 0.002). The median duration from IHCA to ECMO was 40 (IQR 20-75) to 28 (IQR 16-41) minutes (p = 0.134). Pre-survival 25.9% (7/27), post-survival 38.5% (15/39) (p = 0.288).
Schober et al., 2017⁴¹	RS	To assess the qualities of the ECPR-eligible patients	ECPR	CCPR	ECPR selection and 180 days survival	ECPR patients had shorter pre-CPR intervals (0 vs. 1 min; p = 0.013), faster ED admission (38 vs. 56 min; p = 0.31), and younger (46 vs. 60 years; p = 0.04). Survival to discharge 14 (6%).
ter Avest et al., 2022⁴²	RS	Efficacy of HEMS' OHCA ECPR for IHCA	ECPR	n/s	ROSC and eligible ECPR patients	ROSC was 60 (37%) and 15 (9%) asystole deterioration.
Yu et al., 2018⁴³	PCS	Efficacy of ECPR	ECPR	n/s	Survival, ECMO, and ROSC	Favorable outcomes across various subgroups.

Figure 1. The study selection process.

Quality assessment

The NOS Scale was used to assess the quality of the collected studies and considered ten factors: selection, comparability, and outcome and rating each study on a range of 0 to 10. High-quality observational cohort studies constituted those with 7 or more stars; a score of less than four denotes low quality, a score of five to six suggests moderate quality, a score of seven to eight indicates good quality, and a score of nine to 10 denotes extremely good quality.⁴⁴ Four studies were deemed moderate quality, while eight were judged to be of high quality. No studies were deemed to be of low quality. The quality assessment score is shown in Table 1.

The main objective of the current literature review is to examine the efficacy of ECPR compared to conventional CPR in patients with cardiac arrest across various settings. In doing so, we aim to establish the effectiveness of ECPR as a future intervention for either IHCA or OHCA patients. We also identified the existing gaps that would require further research. Based on the synthesis of included studies, our review showed that employing ECPR in both IHCA and OHCA is associated with improved survival rate and corresponding positive neurological outcomes compared to conventional CPR. Our review entails a total of twelve studies comprising observational and retrospective studies, analyzing a cumulative of 2,897 IHCA and OHCA patients. Six studies examined ECPR in OHCA, while the remaining six explored IHA and OHCA. The outcome measures evaluated across the studies mainly comprised ROSC (return of spontaneous circulation), survival, neurological outcomes, eligibility for ECPR, and time to extra corporeal membrane oxygenation (ECMO). Furthermore, among the 12 studies analyzed, five studies reported an increased long-term neurologically intact survival with the use of ECPR, four of which were OHCA,³²^,³⁴^,³⁷^,³⁹ while one evaluated ECPR in IHCA³⁵ (Table 3 in Supplemental Material shows the studies’ design, objectives, interventions, outcomes, and results with neurological outcomes.)

Generally, studies enrolling adult IHCA and OHCA patients reported improved and favorable neurological outcomes associated with ECPR.³⁸^,⁴⁰ A study by Bartos et al. demonstrated that for CPR durations of less than 60 minutes, ECPR was associated with favorable neurological outcomes and survival despite significantly higher metabolic derangement as compared with CCPR.³² Our observations are consistent with findings of another meta-analysis which compared ECPR and CCPR for patients with CA and found that ECPR was related to statistically significant improvement, 30-day survival, and neurologic outcomes for patients with IHCA (RR = 1.60, 95% CI = 1.25-2.06 and RR = 2.69, 95% CI = 1.63-4.46).⁴⁵ The findings revealed no effect on neurological outcomes and survival with ECPR on OHCA patients.⁴⁵ However, another study comparing ECPR and CCPR revealed that neurological outcome and survival were the same in both groups for OHCA.⁴⁶ This finding particularly contradicts the outcomes of the majority of the included studies, which suggest favorable neurological outcomes associated with ECPR relative to CCPR.³⁶^,⁴³

The disparities in these results can be attributed to selection bias in meta-analyses which are due to inclusion of studies with recruitment periods spanning a decade, a period in which technological advancements could have changed a lot in this field. For instance, these advancements have seen CPR guidelines being changed twice and the emergence of advanced mechanical CPR equipment becoming widely adopted.⁴⁷ While our literature review evaluated the criteria under which ECPR should be performed, four studies reported the need to evaluate CA patients for eligibility to see if they fit for ECPR therapy.³⁵^,³⁹^,⁴¹^,⁴² These studies report higher survival associated with carefully selected patients after meeting inclusion criteria.³⁹ These results are significant as they demonstrate the need to make early patient selection conceivable and necessary prior to ECPR therapy. In that regard, Te Avest et al. suggest that one of the factors to consider is the effectiveness of in-hospital ECPR, which appears to be of little importance in rural setups, as potentially ECPR-eligible patients would deteriorate prior to their arrival to the hospital.⁴² This is imperative since as ECPR awareness grows and pre-hospital mechanical CPR is introduced, it is plausible that not only more ECPR eligible cases will present to the emergency department (ED), but may also predict a rise in ECPR ineligible patients.⁴⁸

Time to return of spontaneous circulation, ROSC, CPR duration, and extracorporeal membrane oxygenation were evaluated as an effect of ECPR in this literature review and were reported in most of included articles. Kim et al. showed that longer durations of CPR were associated with decreased neurological outcomes in CCPR compared to with ECPR.³⁶ In contrast, a significant number of patients who were scheduled for ECPR recovered ROSC before or after hospital admission after receiving prolonged CPR.³⁷ In addition, Patricio et al. showed that the ROSC rates associated with ECPR were significantly higher relative to CCPR (77/80 (96%) vs. 30/80 (38%), (p <0.001)).³⁸ Additionally, ECPR effectively reduced the time from OHCA to ECMO under an ECPR-specific program implementation.⁴⁰ (Table 3 provided as in Supplemental Material shows the study design, objectives, interventions, outcomes, and results with neurological outcomes.)

Limitations

The majority of the included studies were observational studies and retrospective in design. This literature review demonstrates existence of a research gap with the absence of randomized control trials, which would raise the level and quality of evidence and close knowledge gaps, since the majority of the current knowledge is derived from single-center observations, and the preponderance of the evidence is derived from case series and cohort studies, making it susceptible to publication bias.⁴⁹ As a result of observational studies’ well-known flaws, it is impossible to draw valid conclusions from primary data due to its high bias risk and potential for producing accurate but false results when combined. This indicates the importance and need for high-quality research that would explore the viability and patient-centered results of employing ECPR in innovative settings, such as via EMS-based or ED-based large, randomized trials, further exploring the usefulness of ECPR for cardiac arrest. Ideally, the design of future research would identify a successful and unified approach to ECPR and develop an algorithm that could be used for both IHCA and OHCA.

Conclusion

Our literature review demonstrates that ECPR has better survival rates and neurological outcomes than standard CPR therapies for CA. ECPR is a development in CPR that allows a bridge to treatment in carefully chosen individuals after meeting the criteria following refractory CA. Furthermore, we establish that individuals who meet the criteria of selection for ECPR are associated with increased neurological outcomes and high survival rates compared to those who are not eligible. This study also demonstrates that, at the moment, ECPR is the most successful in centers with a well-trained multidisciplinary ECMO team of experts. On the other hand, cardiac arrest patients in semi-rural areas and underdeveloped locations are likely to benefit less from ECPR interventions due to the lack of necessary ECPR expertise and infrastructure. Those individuals eligible for ECPR benefit from better neurological outcomes and associated higher survival rates. Therefore, ECPR has the potential to be an effective standard of care for cardiac arrests in the future. There is a need for high quality research in this area to evaluate the feasibility, safety, and efficacy associated with ECPR and the reliability of the findings in our literature review.

Data availability

Underlying data

All data underlying the results are available as part of the article and no additional source data are required.

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