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Nucleated red blood cells are a predictor of mortality in patients under extracorporeal membrane oxygenation

Abstract

Background

The presence of Nucleated Red Blood Cells (NRBCs) in critically ill patients is associated with higher mortality and poor prognosis. Although patients on extracorporeal support such as veno-venous or veno-arterial extracorporeal membrane oxygenation (VV/VA-ECMO) are severely ill, NRBCs have rarely been investigated regarding their predictive value so far.

Methods

As part of a retrospective study, we examined all cardiothoracic surgery patients from July 2019 to September 2020 who received ECMO treatment during their inpatient stay. The aim of this study was to investigate the occurrence of NRBCs during ECMO support in terms of their predictive value for mortality.

Results

In total 30 patients (age at admission: 62.7 ± 14.3 year; 26 male; ECMO duration: 8.5 ± 5.1 days; ICU duration: 18.0 ± 14.5 days) were included. 16 patients (53.3%) died during their inpatient stay. There were no significant differences in demographic characteristics between VA- or VV- ECMO patients. NRBCs occurred in all patients while under ECMO support. NRBC value was significant higher in those who died (2299.6 ± 4356.6 µl) compared to the surviving patients (133.6 ± 218.8 µl, p < 0.001). Univariate analysis found that patients with a cutoff value of ≥ 270 NRBCs/µl during ECMO support were 39 times more likely to die (OR 39.0, 95% CI 1.5–997.5, p < 0.001). 12 out of 13 patients (92.3%) with ≥ 270 NRBCs/µl died. The area under the curve (AUC) of the receiver operating characteristic curve was 0.85 (95% CI 0.69–0.96) with a sensitivity of 75.0% and a specificity of 92.9%.

Conclusion

NRBCs appear to be an accurate biomarker for mortality in patients with ECMO support. They may be helpful in deciding if therapy becomes futile.

Trial registration DRKS00023626 (December 20th 2020).

Background

Patients on ECMO are severely ill patients. In literature, mortality data differ depending on ECMO mode and reason for therapy. According to the Extracorporeal Life Support Organization (ELSO) registry, the survival rate to discharge in adults is 49% (pulmonary 58%, cardiac 45%, ECPR 30%) [1]. With the beginning of an extracorporeal membrane oxygenation there are multiple pre-tests to evaluate risk factors and estimate the probability of death like SAVE-, RESP-, REMEMBER- and ENCOURAGE Score [2,3,4,5]. The risk of mortality for patients undergoing cardiothoracic surgery is estimated with EUROScore II [6]. Unfortunately scores for controlling any kind of ongoing process are still missing. With measuring values such as lactate and bilirubin it is possible to catch hints of organ failure [7, 8]. NRBCs are not found in the peripheral blood of healthy adults. In healthy newborns, NRBCs can be found in the peripheral blood up to five days after birth [9]; in case of premature birth or fetal hypoxia NRBCs can still be found after that period [10]. They are early erythrocyte precursor cells and their presence in peripheral blood is an indicator for either increased erythropoiesis or a defect bone marrow barrier. Regardless of the mechanism, the cause is always stress like hypoxemia, sepsis, or malignancy [11]. The release and secretion of NRBCs is stimulated by Interleukin 3, Interleukin 6 and Erythropoietin [12]. In addition, these cytokines are also released as part of an inflammatory response on ECMO therapy [13].

The presence of NRBCs in the peripheral blood has been described as being associated with mortality in several different populations of patients. Schwartz et al. already described significant correlation between occurrence of NRBCs in peripheral blood and increased mortality back in the 1950’s [14]. Stachon et al. previously depicted the occurrence of NRBCs and their predictive power in cardiothoracic surgery patients [15]. Lehnhardt et al. described the same in burn patients [16]. In addition, the presence of NRBCs was shown to increase mortality even after discharge. It also had a negative predictive effect on hospital readmissions [17].

In 2021, Piggot et al. first demonstrated that NRBCs in neonates and children < 1 year of age treated with VA—ECMO are a useful marker for mortality [18]. To the best of our knowledge there are currently no studies available that have investigated the occurrence and prognostic significance of NRBCs in adult patients while on ECMO except for a subgroup analysis in patients with ARDS [19]. Not to be neglected, however, is the question if NRBCs can still be seen as a mortality predictor in patients with known hematological disorder [20].

The aim of our study was to investigate the occurrence and levels of NRBCs in cardiothoracic patients on ECMO in terms of their prognostic significance regarding patient mortality.

Methods

Ethical aspects, study population

The present study was performed at the University Hospital Bergmannsheil Bochum (which is a registered ECMO center). Retrospectively, the data of 30 patients of our intensive care unit were examined regarding NRBC levels. Blood samples were taken daily at the same point of time in patients with extracorporeal support procedures. 30-day-mortality after decannulation was investigated. Most patients had undergone cardiac surgery (Coronary artery bypass grafting, Valve or Aortic surgery) except for two patients who were treated conservatively for pulmonary embolism. Exclusion criteria were age under 18 years, ECMO duration less than 24 h and patients with history of hematologic disease.

After obtaining permission from the local ethics committee (No.: 20–706430), the study was registered in the German clinical Trial register (German Clinical Trials Register-No: DRKS00023626, retrospectively registered, December 20th 2020, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00023626). No informed consent for retrospective, anonymous data are required and informed consent was waived by the ethics committee.

Data were collected in the period from July 2019 to September 2020 from the in-house patient data management system (Medico, Cerner, Germany).

All patients were treated with the following ECMO systems: Cardiohelp, Rotaflow (Getinge Group) and Novalung (Fresenius Medical Care). Cannulation strategies were chosen regarding the physicians’ preference and the clinical setting such as femoral or axillary arterial and femoral or internal jugular venous cannulation.

Laboratory tests

The blood samples were taken daily with a commercially available EDTA tube. The determination of NRBCs was performed with the UniCel DxH 600—Coulter Cellular Analysis System (Sysmex, Kobe, Japan). Counts are reported in NRBC cells (n)/µl.

Statistical analysis

Categorical characteristics are shown as total and percentage and compared using Exact Fisher’s test. Metric characteristics are described based on mean, median, standard deviation, interquartile range and minimum and maximum compared using the Mann–Whitney U test. Level of significance was assumed p < 0.05. To determine the cutoff, we used the Youden-Index as well as Liu’s method and Nearest-method. Odd`s ratio as probability of mortality was calculated. NRBCs discriminatory power was assessed by calculating the area under the receiver operating characteristic (ROC) curve. To visualize the survival, we used the Kaplan—Meier curve. Stata/IC 16.1 software (StataCorp 4905 Lakeway Drive College Station, TX 77845 USA) was used for analyses.

Results

A total of 30 patients were included in the analysis. Mean age was 62.7 years (± 14.3). The study group consisted of 26 men and 4 women.

All patients were in a life-threatening condition and needed extracorporeal life support either as veno-venous- (VV) or veno-arterial- (VA) device for more than 24 h. A number of 12 patients was treated with VV-ECMO, 18 patients needed a VA-ECMO. Additionally, 3 out of 30 were supported with an intra-aortal balloon pump (IABP), 4 others had a mechanical ventricular support (MVS). In our institution, we use the IMPELLA-family (Abiomed, Danvers, MA). There were no statistic significant differences regarding mortality when IABP (p = 1.000) or MVS (p = 0.336) was used.

All patients underwent cardiac surgery except for two patients suffering from pulmonary embolism who were treated conservatively. The cause for device implantation was multifactorial in a lot of patients so that multiple mentions are possible. Most patients were in an acute life-threatening condition: under CPR (10), post—cardiotomy (10), unbalanced gas exchange (10), right heart failure (5) and pulmonary embolism (2). Reasons for ECMO therapy and mode of operation as well as baseline characteristics, laboratory values and demographics are shown in Table 1. Of these 30 patients 14 survived a 30-day-follow-up after decannulation. While still on ECMO 13 out of 16 patients died. 3 patients died shortly after decannulation. Metric characteristics showed no significant differences between survivors and non survivors.

Table 1 Demographics and clinical data

NRBCs as mortality predictor

NRBC values were higher in those who died (2299.6 ± 4356.6 µl) compared to those who survived (133.6 ± 218.8, p < 0.001) (Table 2, Fig. 1). We used the Youden-Index as well as Liu’s method and “Nearest method” to define the best cutoff for mortality prediction. All three statistical procedures defined NRBC count with more than 270 µl on at least one day on ECMO as significant. 13 patients reached or exceeded this cutoff, 12 (92.3%) of these 13 patients died. In contrast, patients below this cutoff showed a significant lower mortality [4 (23.5%) of 17, p < 0.001]. Patients with a cutoff value of ≥ 270 NRBCs/µl during ECMO support were 39 times more likely to die (OR 39, 95% CI 1.52–997.54, p < 0.001) (Table 3). ROC curve evaluating NRBCs as a predictor of mortality, showed an AUC of 0.85 (95% CI 0.69–0.96, p < 0.001), with a sensitivity of 75% and specificity of 92.9%, and positive and negative predictive values of 92.3% and 76.5%, respectively (Fig. 2). Kaplan–Meier curve shows the overall survival (Fig. 3). Additional File 1 Figure S1 shows the distribution of NRBC/µl over time.

Table 2 NRBCs count(/µl) during ECMO
Fig. 1
figure 1

NRBCs concentrations found in peripheral blood of patients who either died or survived ECMO procedures

Table 3 Mortality odds ratio (95%CI)
Fig. 2
figure 2

Area under the receiver operating characteristic curve (AUROC) for NRBC count ≥ 270 µl as predictor of mortality while on ECMO

Fig. 3
figure 3

Kaplan—Meier survival curve of ECMO patients according to NRBCs count

Discussion

ECMO treatments are predominantly high-risk, high-cost, and often ethically debatable [21,22,23] therapeutic options. During installation as well as during therapy, several complications may occur such as hemorrhage, limb ischemia, neurological damage, liver, or kidney failure [24,25,26]. At the same time, these procedures provide physicians with a tool to support patients with either respiratory or circulatory failure.

The occurrence of NRBCs in the peripheral blood is pathophysiological due to a higher erythropoietic pressure and the failure of the spleen to clear these precursor cells. Since circumstances such as systemic inflammatory reactions, hypoxia, massive hemorrhage, and cardiac failure increase erythropoietic pressure, the appearance of NRBCs indicates a disturbance of homeostasis [17]. Although the exact mechanism is not clear yet, the appearance of these progenitor cells can thus be taken as an indicator of ongoing organ failure. It is therefore not surprising that, in contrast to other studies, we were able to detect NRBCs in the peripheral blood of all our patients, which reflects the severity of our patients' diseases. However, despite the fact, that no causality can be inferred from a retrospective observational study, the relationship between the occurrence of NRBCs and the higher probability of death is plausible. Thus, our results support the context of other previous studies, which have shown that NRBCs can serve as prognostic markers.

Stachon et al. pointed out the prognostic significance in patients who underwent cardiothoracic surgery [15]. Lehnhardt et al. showed the same in burn patients. In their study, the sole presence of NRBCs—irrespective of the number of cells—was a predictor of mortality with an Odd’s ratio of 8.3 (CI 95% 4.5–15.3) [16]. Even at the time of admission in the emergency department higher blood levels of NRBCs seem to be associated with higher mortality [27]. Furthermore, for post discharge outcome in critically illness survivors NRBC counts seem to have a prognostic value. Odds’ ratio for 90-day-mortality post-discharge in patients with more than 200 µl NRBCs was 3.72 (95% CI 2.16–6.39) [17].

In our study, patients in the acute phase of illness with cardiocirculatory and/ or respiratory failure requiring ongoing extracorporeal support were studied. Piggott et al. demonstrated an NRBCs’ increase greater than 50% after ECMO decannulation in children was associated with higher inpatient mortality (OR 17.1, 95% CI 3.1–95.1, p = 0.001) [16]. Therefore, our results fit closely with those of the limited number of previous studies.

When evaluating the cutoff for NRBCs we saw a 39 times greater risk for death when NRBCs reached or passed 270 µl. Furthermore, the ROC curve of NRBCs under ECMO therapy reached an AUC of 0.85. In addition, significantly higher levels of nucleated red blood cells were detected in the blood of the deceased patients. In summary, all this indicates NRBCs as a very strong predictor for mortality in critically ill patients independent of the ECMO mode. Besides, it is an advantage that NRBCs can be routinely determined every day. It is easily available and low of cost.

As a part of future investigations, we would like to incorporate NRBC count, respectively, a defined cutoff in a clinical mortality score. There are some existing mortality scores like EuroSCORE II for cardiothoracic patients [6], RESP Score for patients undergoing VV-ECMO [3] or SAVE Score for those with VA-ECMO [2], just to name a few of them. Some of them are used to estimate whether a device should be implemented or not, most scores are ascertained for one time before implementation based on pre ECMO values and, therefore, not flexible [28]. None of these ECMO scores, nor any of the intensive care scores such as Apache II or SAPS II, despite their good prognostic strength, include the incidence and level of NRBCs [29]. In the past there have been a few attempts to integrate NRBCs e.g., in APACHE II with reliable results [30, 31]. Stachon et al. found for their modified APACHE II score an area under curve about 0.91 compared to 0.87 and 0.72 for the APACHE II and NRBCs alone [30]. To validate such a modified risk score further prospective studies are needed.

Even though we only included a small number of cases in our study, there is a very strong trend that this parameter is suitable to measure mortality in the context of ECMO therapy.

With a routine daily review of NRBCs implemented into a scoring system, perhaps a flexible tool could be created to evaluate the patients’ process and give physicians a chance to take a closer look at the patient before further deterioration occurs. While further large prospective studies have yet to demonstrate whether NRBCs can serve as a marker to detect mortality independent of ECMO mode, based on our results, we can say that while NRBCs are not new in business, they appear to be old but gold.

Conclusion

In our study group, we were able to show that the level of nucleated red blood cells is an excellent marker for predicting mortality on ECMO. Of course, diagnosis and treatment decisions in the context of ECMO procedures should never be based on one laboratory value, but decision making in the context of a scoring system in the ethical dilemma "is the patient still alive or am I just keeping him alive" should be the goal for future studies. In terms of its prognostic significance, such a score should include the level and progression of NRBCs.

Limitations

There are several limitations of our study. Due to the retrospective design of our study and the small number of patients further studies are necessary. Prospective studies might also be able to reveal the mechanism(s) behind the observed association. Also, we investigated 26 male and only 4 female patients. We assume that the prognostic value for both genders is the same.

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

BMI:

Body Mass Index

CABG:

Coronary artery bypass grafting

CI:

Confidence interval

COPD:

Chronic obstructive pulmonary disease

CPR:

Cardiopulmonary resuscitation

CRP:

c-reactive protein

ECMO:

Extracorporeal membrane oxygenation

eCPR:

extracorporale cardiopulmonary reanimation

ELSO:

Extracorporeal life support organization

GFR:

Glomerula filtration rate

ICU:

Intensive care unit

IQR:

Interquartile range

M:

Mean

NRBCs:

Nucleated red blood cells

OR:

Odds ratio

PCS:

Post cardiotomy syndrome

PAE:

Pulmonary arterial embolism

pRBCs:

Packed red blood cells

RESP Score:

Respiratory extracorporeal membrane oxygenation survival prediction score

SAPS II:

Simplified acute physiology score

SD:

Standard deviation

SAVE Score:

Survival after veno-arterial extracorporeal membrane oxygenation score

V-A:

Veno - arterial

V-V:

Veno - venous

WBC:

White blood cell count

References

  1. Extracorporeal Life Support Organization (ELSO) registry: https://www.elso.org/Registry/ELSOLiveRegistryDashboard.aspx, accessed on 05/26/2022

  2. Schmidt M, Burrell A, Roberts L, Bailey M, Sheldrake J, Rycus PT, Hodgson C, Scheinkestel C, Cooper DJ, Thiagarajan RR, Brodie D, Pellegrino V, Pilcher D. Predicting survival after ECMO for refractory cardiogenic shock: the survival after veno arterial -ECMO (SAVE) score. Eur Heart J. 2015;36:2246–56.

    Article  CAS  PubMed  Google Scholar 

  3. Schmidt M, Bailey M, Sheldrake J, Hodgson C, Aubron C, Rycus PT, Scheinkestel C, Cooper DJ, Brodie D, Pellegrino V, Combes A, Pilcher D. Predicting survival after Extracorporeal membrane oxygenation for severe acute respiratory failure. The respiratory extracorporeal membrane oxygenation survival prediction (RESP) score. Am J Respir Crit Care Med. 2014;189(11):1374–82.

    Article  PubMed  Google Scholar 

  4. Wang L, Yang F, Wang X, Xie H, Fan E, Ogino M, Brodie D, Wang H, Hou X. Predicting mortality in patients undergoing VA-ECMO after coronary artery bypass grafting: the REMEMBER Score. Crit Care. 2019;23:11.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Muller G, Flecher E, Lebreton G, Luyt CE, Trouillet CE, Bréchot N, Schmidt M, Mastroianni C, Chastre J, Leprince P, Anselmi A, Combes A. The ENCOURAGE mortality risk score and analysis of long-term outcomes after VA-ECMO for acute myocardial infarction with cardiogenic shock. Intensive Care Med. 2016;42:370–8.

    Article  PubMed  Google Scholar 

  6. Nahef SAM, Roques F, Sharples L, Nilsson J, Smith C, Goldstone AR, Lockowandt U. EuroSCORE II. Eur J Cardiothorac Surg. 2012;41:734–45.

    Article  Google Scholar 

  7. Kaestner F, Rapp D, Trudzinski FC, Olewczynska N, Wagenpfeil S, Langer F, et al. High serum bilirubin levels, NT-pro-BNP, and lactate predict mortality in long term, severely Ill respiratory ECMO patients. ASAIO J. 2018;64(2):232–7.

    Article  CAS  PubMed  Google Scholar 

  8. Laimoud M, Alanazi M. The clinical significance of blood lactate levels in evaluation of adult patients with veno-arterial extracorporeal membrane oxygenation. Egypt Heart J. 2020;72:74.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Miller DR, Baehner RL. Blood diseases of infancy and childhood. 7th ed. St Louis: Mosby; 1995. p. 39–40.

    Google Scholar 

  10. Hanlon-Lundberg KM, Kirby RS. Nucleated red blood cells as a marker of acidemia in neonates. Am J Obstet Gynecol. 1999;181:196–201.

    Article  CAS  PubMed  Google Scholar 

  11. Danise P, Maconi M, Barrella F, Di Palma A, Avino D, Rovetti A. Evaluation of nucleated red blood cells in the peripheral blood of hematological diseases. Clin Chem Lab Med. 2012. https://doi.org/10.1515/cclm.2011.766.

    Article  Google Scholar 

  12. Stachon A, Bolulu O, Holland-Letz T, Krieg M. Association between nucleated red blood cells in blood and the levels of erythropoietin, interleukin 3, interleukin 6, and interleukin12p70. Shock. 2012;24(1):34–9.

    Article  Google Scholar 

  13. Millar JE, Fanning JP, McDonald CI, McAuley DF, Fraser JF. The inflammatory response to extracorporeal membrane oxygenation (ECMO): a review of the pathophysiology. Crit Care. 2016;20(1):387.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Schwartz SO, Stansbury F. Significance of nucleated red blood cells in peripheral blood: analysis of 1496 cases. JAMA. 1954;154(16):1339.

    Article  CAS  Google Scholar 

  15. Stachon A, Böning A, Krismann M, Weisser H, Laczkovics A, Skipka G, Krieg M. Prognostic significance of the presence of erythroblasts in blood after cardiothoracic surgery. Clin Chem Lab Med. 2001;39(3):239–43.

    Article  CAS  PubMed  Google Scholar 

  16. Lehnhardt M, Katzy Y, Langer S, Druecke D, Homann HH, Steinstraesser L, Steinau HU, Stachon A. Prognostic significance of erythroblasts in burns. Plastic and reconstructive surgery. Plast Reconstr Surg. 2005;115(1):120.

    Article  CAS  PubMed  Google Scholar 

  17. Purtle SW, Horkan CM, Moromizato T, Gibbons FK, Christopher KB. Nucleated red blood cells, critical illness survivors and postdischarge outcomes: a cohort study. Crit Care. 2017;21(1):154.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Piggott KD, Norlin C, Laviolette C, Turner J, Lewis L, Soliman A, Hebert D, Pettitt T. Nucleated red blood cells as a biomarker for mortality in infants and neonates requiring veno-arterial extracorporeal membrane oxygenation for cardiac disease. Perfusion. 2021. https://doi.org/10.1177/02676591211050607.

    Article  PubMed  Google Scholar 

  19. Menk M, Giebelhäuser L, Vorderwülbecke G, Gassner M, Graw JA, Weiss B. Nucleated red blood cells as predictors of mortality in patients with acute respiratory distress syndrome (ARDS): an observational study. Ann Intensive Care. 2018;8(1):42.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Amundsen EK, Binde C, Christensen EE, Klingenberg E, Kvale D, Holten AR. Prognostic value of nucleated rbcs for patients with suscpected sepsis in the emergency department: a single-center prospective cohort study. Crit Care Expl. 2021. https://doi.org/10.1097/CCE.0000000000000490.

    Article  Google Scholar 

  21. Karagiannidis C, Bein T, Weber-Carstens S. Indikationen und grenzen der ECMO therapie. Med Klein Intensivmed Notfallmed. 2019;114:207–13.

    Article  CAS  Google Scholar 

  22. Lansik-Hartgring AO, van Minnen O, Vermeulen KM, van den Bergh WM. Hospital costs of extracorporeal membrane oxygenation in adults: a systematic review. Pharmacoecon Open. 2021;5(4):613–23.

    Article  Google Scholar 

  23. Mishra V, Svennevig JL, Bugge JF, Andresen S, Mathisen A, Karlsen H, Khushi I, Hagen TP. Cost of extracorporeal membrane oxygenation: evidence from the Rikshospitalet University Hospital, Olso, Norway. Eur J Cardiothoracic Surg. 2010;37(2):339–42.

    Google Scholar 

  24. Bonicolini E, Martucci G, Simons J, Raffa GM, Spina C, Lo Coco V, Arcadipane A, Pilato M, Lorusso R. Limb ischemia in peripheral veno-arterial extracorporeal membrane oxygenation: a narrative review of incidence, prevention, monitoring, and treatment. Crit Care. 2019;23:266.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Lorusso R, Belliato M, Mazzeffi M, Di Mauro M, Taccone FS, Parise O, Albanawi A, Nadwani V, McCarthy P, Kon Z, Menaker J, Johnson DM, Gelsomino S, Herr D. Neurological complications during veno-venous extracorporeal membrane oxygenation: does the configuration matter? A retrospective analysis of the ELSO database. Crit Care. 2021;25:107.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Chen H, RG Y, Yin NN, Zhou JX. Combination of extracorporeal membrane oxygenation and continuous renal replacement therapy in critically ill patients: a systematic review. Crit Care. 2014;18:675.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Narci H, Oktay MM, Airyk C, Cimen MBY. Nucleated red blood cells as predictor of all-cause mortality in emergeny department. Am J Emerg Med. 2021;46:335–8.

    Article  PubMed  Google Scholar 

  28. Fisser C, Rincon-Guiterrez LA, Enger TB, Taccone FS, Broman LM, Belliato M, Nobile L, Pappalardo F, Malfertheiner MV. Validation of prognostic scores in extracorporeal life support: a multi-cenric retrospective study. Membranes. 2021;11:84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Le Gall J-R, Lemeshow S, Saulnier F. A new simplified acute physiology Score (SAPSII) based on a European/North American multicenter study. JAMA. 1993;270:2957–63.

    Article  PubMed  Google Scholar 

  30. Stachon A, Segbers E, Holland-Letz T, Kempf R, Hering S, Krieg M. Nucleated red blood cells in the blood of medical intensive care patients indicate increased mortality risk: a prospective cohort study. Crit Care. 2007;11:62.

    Article  Google Scholar 

  31. Xu C, Wang J, Jin X, Yuan Y, Lu G. Establishment of a predictive model for outcomes in patients with severe acute pancreatitis by nucleated red blood cells combined with Charlson complication index and APACHE II score. Turk J Gastroenterol. 2020;31(12):936–41.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We acknowledge support by the Open Access Publication Funds of the Ruhr-University Bochum.

Funding

Open Access funding enabled and organized by Projekt DEAL. Institutional resources only.

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Authors

Contributions

SL and DMB jointly conceived the study. SL and DMB designed and implemented the analysis with assistance from PZ. SL and DMB wrote the manuscript. DB provided data. PZ, AB, MB and JS edited the manuscript and provided conceptual advice. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Sebastian Loesaus.

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Ethics approval and consent to participate

The study was reviewed and approved by the Medical Faculty`s ethics committee (No.: 20–706430 Medical Faculty of the Ruhr-University, Bochum, Germany) and registered in the German clinical trial database (German Clinical Trials Register-No.: DRKS00023626). Requirement for consent was waived because the data were analyzed anonymously.

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Supplementary Information

Additional file 1. Figure S1

Distribution of NRBCs/μl over time

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Loesaus, S., Zahn, P.K., Bechtel, M. et al. Nucleated red blood cells are a predictor of mortality in patients under extracorporeal membrane oxygenation. Eur J Med Res 28, 270 (2023). https://doi.org/10.1186/s40001-023-01243-y

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