Critical Care

Association between resuscitation in the critical care resuscitation unit and in-hospital mortality

a b s t r a c t

Introduction: Patients who present in shock have high Expected mortality and early resuscitation is crucial to im- prove their outcomes. The Critical Care Resuscitation Unit (CCRU) is a specialized unit at the University of Mary- land Medical Center (UMMC) that prioritizes early resuscitation of critically ill patients. We hypothesized that Lactate clearance and reduction of Sequential Organ Failure Assessment score during CCRU stay would be associated with lower in-hospital mortality.

Methods: We performed a retrospective analysis of adult patients who were admitted to the CCRU between 01/ 01/2018-12/31/2018 and had a diagnosis of severe shock, determined by serum lactate >=4 mmol/L. We excluded patients who died during CCRU stay. We used multivariable logistic regression to evaluate the association between lactate clearance and reduction in SOFA scores during CCRU stay and in-hospital mortality.

Results: Out of 1740 patients admitted to the CCRU in 2018, 172 (10%) had serum lactate >=4 mmol/L. Twenty-two (13%) patients died during their CCRU stay. Our primary analysis included 129 patients with lactate clearance data and 136 patients with SOFA data. Average patients’ age was 54 years, and median length of stay in the CCRU was 6 h 55 min. The average lactate and SOFA score on admission were 7.4 (3.8) mmol/L and 8.3 (4.7), re- spectively. Average lactate clearance was 1.9 (3.1) and average SOFA score reduction was 0.2 (2.9). In multivar- iable logistic regressions evaluating SOFA score and lactate separately, SOFA score reduction during CCRU stay was associated with lower in-hospital mortality (OR 0.83, 95% CI: 0.70-0.97) but lactate clearance was not (OR 0.90, 95% CI 0.78-1.03). In forward stepwise multivariable analysis containing both SOFA score and lactate values, SOFA score clearance during CCRU stay was still associated with decreased in-hospital mortality (OR 0.84, 95% CI 0.72-0.98).

Conclusions: Care in the CCRU is more effective at reducing lactate than SOFA scores in patients with severe shock. However, SOFA score reduction in the resuscitation phase during the CCRU stay was associated with decreased odds of in-hospital mortality in this group of patients. Further studies are necessary to confirm our observations.

(C) 2022

  1. Introduction

Patients with critical illness, shock, and progressive organ dysfunc- tion have high rates of morbidity and mortality. A previous study sug- gested that the rate of morbidity and mortality rises with the number

? Presented at the Society of Critical Care Medicine, April 2022.

* Corresponding author.

E-mail address: [email protected] (T. Miller).

of dysfunctional organ systems [1]. Therefore, early and effective resus- citation plays a crucial role in improving outcomes for these patients.

Because of the heterogeneous nature of critical illness, physiologic scores are often used to standardize, compare, and assess severity of ill- ness, in addition to predicting mortality. The Sequential Organ Failure Assessment score is one such physiologic measure that was originally developed to describe the degree of organ dysfunction [2]. Subsequent studies have shown that increasing SOFA score is associated with higher mortality in critically ill patients [3]. Serum lactate level, similarly, has been used as a surrogate for severity of critical illness

0735-6757/(C) 2022

[4,5,6]. In fact, lactate levels have been compared to physiologic scores and found to have similar ability to predict mortality, with higher levels associated with higher mortality, and lactate clearance has been associ- ated with better outcomes in patients with sepsis and septic shock [7,8]. Early resuscitative measures in the Emergency Department (ED) are crucial as studies have shown that it is during this time that physiologic scores of organ dysfunction are reduced at a greater rate than at any other time during hospitalization. Furthermore, higher physiologic scores on hospital admission are associated with greater mortality,

stressing the importance of early resuscitation [9].

The Critical Care Resuscitation Unit (CCRU) serves as the accepting unit for critically ill patients who are transferred from other hospitals to the University of Maryland Medical Center (UMMC). The role of the CCRU is to expedite transfer to definitive care only available at a tertiary care medical center and to facilitate early resuscitation measures for these critically ill patients [10]. The CCRU has been shown to be associ- ated with faster transport times and lower mortality when compared with other traditional Intensive care units at our institution [11]. However, the association between early resuscitation in the CCRU and improving physiologic scores and subsequent mortality is unknown.

Patients who present in severe shock (defined as serum lactate >=4 mmol/L) have high expected mortality and early resuscitation is crucial to improve their outcomes. In this study, we aimed to investigate the as- sociation of resuscitation in the CCRU and patients’ outcome. We hy- pothesized that lactate clearance and reducing Sequential organ failure assessment score during CCRU stay would be associated with lower in-hospital mortality for these patients.

  1. Methods
    1. Study setting

The CCRU is a 6 bed ICU-based resuscitation unit that is located sep- arate from the Emergency Department within the University of Mary- land Medical Center’s R Adams Cowley Shock Trauma Center. It is staffed continuously by one emergency medicine and critical-care trained attending physician, one Advanced Practice Provider (APP), three admitting nurses, and a charge nurse who may also admit new pa- tients as needed. The CCRU and specialty referral attending physicians discuss any potential transfers requests with the referring clinicians, making simultaneous management recommendations for patients being accepted for transfer. While the patient is in transit to the CCRU, the team performs a “huddle” to develop the plan of care for the patient, incorporating specialty physicians’ guidance. On arrival to their room, the patients are evaluated immediately by the attending physicians, the APP/resident, at least two nurses, and a technician. Members of any specialty teams such as Stroke Neurology, Cardiac Surgery, Neuro- surgery, etc. are also present at bedside to evaluate and intervene as clinically indicated. This staffing model and level of preparation allows an effective resuscitation plan to be implemented early in the patient’s hospital course. After stabilization patients are transferred from the CCRU to an appropriate available bed with their primary accepting ser- vice. Under few circumstances, patients are discharged home directly from the CCRU, but also from the patients’ primary accepting services. Patients who were discharged home directly from the CCRU were also included in the study.

    1. Study design and patient selection

This was a retrospective chart analysis of adult patients who were admitted to the CCRU between 01/01/2018-12/31/2018. All adult pa- tients admitted to the CCRU were included in the study. At our institu- tion, trauma patients are admitted through a separate Trauma Resuscitation Unit (TRU), so no trauma patients were included in this study. When patients first arrive at the CCRU, the clinical policy suggests

that all patients will have repeated serum laboratory assessments, and the types of serum laboratory tests are determined as clinically needed by the bedside CCRU clinicians. Lactate values and SOFA Score compo- nents are routinely collected, as part of standard clinical care, on admis- sion to the unit. When patients are in shock and their Serum lactate levels at arriving at the CCRU is greater than 2 mmol/L, CCRU policy also requires a repeat set of Laboratory measurements 4-6 h later or upon leaving the CCRU, whichever is sooner. Patients were included in this study if they were in severe shock upon CCRU arrival, which we de- fined as having serum lactate levels at arrival at the CCRU of 4 mmol/L or higher. This criteria for severe shock was chosen because in this context it identifies critically ill patients with high likelihood of mortality from a heterogeneous patient population. We excluded patients who died in the CCRU both because these patients were considered to be “too sick” to respond to intensive Resuscitative efforts and because many of these patients have life support being withdrawn by next of kin after discussions with the CCRU and the specialty physicians about patients’ prognosis. Patients who died before leaving the CCRU also did not have lactate values or SOFA Scores that could be calculated on leaving the unit. We also excluded patients who did not have both serum lactate values or both SOFA scores at arrival and at leaving the CCRU.

    1. Physiologic measures

Two different physiologic measures were used as independent vari- ables: reduction of the SOFA score and lactate clearance. Both of these variables were calculated as the first value obtained on arrival minus the last level obtained prior to the patient leaving the CCRU or immedi- ately upon leaving.

    1. Outcome measures

The primary outcome was in-hospital mortality. Secondary out- comes were the magnitude of lactate clearance and SOFA score reduc- tion during CCRU stay.

    1. Data collection

Data were collected from review of the patients’ electronic medical records at our institution. We collected patients’ demographics, comor- bidities (past medical history), the components of the SOFA score, lac- tate values, interventions performed while in the CCRU, and survival to CCRU and hospital discharge. Research team members were trained by the principal investigator and the senior research team leader. Accu- racy was verified by training with blocks of 10 patient charts until there was >90% agreement between research team member and senior re- searcher. Data were collected in a standardized Microsoft Excel spread- sheet (Microsoft Corp, Washington, USA). Patients who had missing data that made it impossible to calculate SOFA Score (missing more than 2 components) or lactate clearance were excluded from analysis.

    1. Statistical analysis

We used descriptive analysis with mean (+/- Standard Deviation (SD)] or median (interquartile range [IQR]) for our continuous vari- ables, and frequency (percentage) for our categorical variables, as ap- propriate. Unpaired Student’s t-test, Mann Whitney U test were used to compare means or median of continuous variables, according to their patterns of distributions. Normal distribution was evaluated by inspecting histograms of lactate and SOFA values. Pearson’s Chi-square or Fisher’s exact tests were used to compare categorical variables when appropriate.

In order to identify association of demographic, clinical factors with mortality, a forward stepwise multivariable logistic regression was used. All factors were chosen a priori and were entered into the model. List of independent variables used for our multivariable logistic

regression was provided in Appendix 1. The results from our multivari- able logistic regressions were presented with Odd Ratio (OR), 95% Con- fidence Interval (95% CI) and p-value. Since there were different

Table 1

Patient characteristics.

All patients Survivors Non-survivors

numbers of patients who had lactate clearance values and SOFA score

reduction values, we first performed multivariable logistic regressions

Number of Patients Age, mean (SD)


54.4 (15.7)


55.1 (16.6)


52.8 (13.8)

to evaluate the association of initial lactate levels, lactate clearance

Female, n (%)

74 (49.3%)

55 (53.4%)

19 (40.4%)

and mortality separately from initial SOFA score and SOFA score reduc- Past Medical History, n (%)

considered to have good fit of the independent variables. An AUROC value of 1 would indicate a model with perfect discriminatory capability between the dichotomous outcome, while an AUROC value of 0.5 sug- gests discrimination no better than chance. Since we used a multivari- able logistic regression, we used the Variance Inflation Factor (VIF) test to avoid potential multicollinearity between variables. Any inde- pendent variable with VIF > 5 is considered to have multicollinearity with other factors and would be removed from the model.

Descriptive analyses and multivariable regressions were performed with Minitab version 19 (Minitab Inc., State College, PA). We considered all statistical analysis tests with 2-tail p-value <0.05 as statistically significant.

  1. Results
    1. Patient characteristics

A total of 1740 patients were admitted to the CCRU in 2018, of whom 172 (10%) had serum lactate >=4 mmol/L (Fig. 1). Twenty-two (13%) pa- tients died during their CCRU stay and were excluded from the analysis; their characteristics were presented in Appendix 2. Seventeen of these patients (78%) died after care was withdrawn while the patient was in the CCRU. Our primary analysis included a total of 129 patients with lac- tate clearance data and 136 patients with SOFA data. Average patients’ age was 54.4 (15.7) years, and median length of stay in the CCRU was 6 h and 55 min (IQR 3:54,17:18). The average lactate and SOFA score on admission were 7.4 (3.8) mmol/L and 8.3 (4.7), respectively. Average lactate clearance was 1.9 (3.1) and average SOFA score reduction was

Image of Fig. 1

Fig. 1. Patient selection diagram.

Arrival Lactate (mmol/L) 7.4 (3.8) 6.5 (3.0) 9.3 (4.6)

Lactate Change in CCRU -1.9 (3.1) -2.1 (2.6) -1.6 (3.9)

tion. We subsequently performed a forward stepwise multivariable lo-


54 (36%)

47 (45.6%)

7 (14.8%)

gistic regression to assess the association of both lactate, lactate


35 (23.3%)

29 (28.1%)

6 (12.8%)

clearance, SOFA score, SOFA score reduction by including them in the

Liver Disease

22 (14.7%)

13 (12.6%)

9 (19.1%)

same model.

The performance of the multivariable logistic regression was assessed with the Hosmer-Lemeshow’s goodness-of-Fit test and the

Kidney Disease

Cardiac Disease Shock Index

White Blood Cell count

36 (24%)

42 (27.3%)


17.1 (8.6)

26 (25.2%)

30 (29.1%)


17.4 (8.7)

10 (21.3%)

11 (23.4%)


16.6 (8.4)

Area Under the Receiver operating characteristic curve . A lo-

(counts/uL), mean (SD)

gistic regression with p-value of the Hosmer-Lemeshow test >0.05 is

Hemoglobin (g/dL), mean (SD)

11.1 (2.8)

11.0 (2.9)

11.3 (2.7)

Arrival SOFA Score 8.3 (4.7) 7.1 (4.2) 10.9 (4.5)

SOFA Change in CCRU -0.2 (2.9) -0.4 (2.7) 0 (3.3)

CCRU Length of Stay, hours (IQR) 6.9 (3.9-17.3) 7.9 (2.9-18.3) 5.7 (4.0-13.0)

Invasive Mechanical Ventilation, 93 (62%) 58 (56.3%) 35 (74.5%) n (%)

Requiring Vasopressors, n (%) 79 (52.7%) 44 (42.7%) 35 (74.5%)

0.2 (2.9) (Table 1). Patients in severe shock who survived their CCRU stay had a subsequent in-hospital mortality rate of 31.3%.

Further characteristics between hospital survivors and non- survivors were presented in Table 1.

A large proportion of these patients received interventions during their stay in the CCRU (63.3%, 95/150) (Table 2). The most common in- tervention was intubation (22%, 33/150 patients), emergent surgical in- tervention (16.7%, 25/150 patients), Extracorporeal Membrane Oxygenation (14.7%, 22/150 patients), and Continuous Renal Replace- ment Therapy (14%, 21/150 patients).

    1. Main results

Arrival SOFA Score was associated with higher mortality (OR 1.26, 95% CI: 1.13-1.41) and each point of SOFA Score reduction was associ- ated with reduced in-hospital mortality (OR 0.83, 95% CI: 0.70-0.97). Arrival lactate was also associated with higher mortality (OR 1.24, 95% CI: 1.10-1.41) but lactate clearance was not significantly associated with reduced in-hospital mortality (OR 0.90, 95% CI: 0.78-1.03). The P-value for the Hosmer-Lemeshow test was 0.53 in the lactate regres- sion and 0.58 in the SOFA Score regression, demonstrating high

Table 2

Interventions done in the CCRU separated by survival.

Intervention, N (%)

All patients




6 (4%)

5 (3.3%)

1 (0.7%)


16 (10.7%)

10 (6.7%)

6 (4%)

Continuous Renal Replacement

Therapy (CRRT)

21 (14%)

10 (6.7%)

11 (7.3%)

Intra Aortic Balloon Pump (IABP)

3 (2%)

3 (2%)

0 (0%)


33 (22%)

23 (15.3%)

10 (6.7%)

interventional radiology

10 (6.7%)

9 (6%)

1 (0.7%)

Operating Room

25 (16.7%)

19 (12.7%)

6 (4%)

Cerebrovascular Thrombectomy

1 (0.7%)

1 (0.7%)

0 (0%)

Hyperbaric Therapy

1 (0.7%)

1 (0.7%)

0 (0%)

Intermittent Hemodialysis

1 (0.7%)

0 (0%)

1 (0.7%)

Cardiac Cath

1 (0.7%)

1 (0.7%)

0 (0%)


6 (4%)

4 (2.7%)

2 (1.3%)


4 (2.7%)

4 (2.7%)

0 (0%)

VV ECMO = veno-venous extracorporeal membrane oxygenation, VA ECMO = Veno- Atrial Extracorporeal Membrane Oxygenation, EVD = External ventricular drainage, EGD = esophagogastroduodenoscopy.

Table 3

Results of two separate regressions showing association between SOFA score reduction and lactate clearance and in-hospital mortality.

SOFA score

Lactate clearance

Odds ratio

95% CI



Odds ratio

95% CI





(0.97, 1.03)




(0.96, 1.02)



Arrival SOFA

Arrival Lactate


(1.13, 1.41)




(1.10, 1.41)



SOFA Reduction

Lactate Clearance


(0.70, 0.97)




(0.78, 1.03)





(0.96, 1.06)




(0.95, 1.05)





(0.93, 1.28)




(0.92, 1.28)





(0.10, 0.92)




(0.09, 0.79)





(0.35, 3.42)




(0.23, 2.15)



Liver Disease


(0.29, 3.19)




(0.25, 2.85)



Kidney Disease


(0.30, 2.51)




(0.59, 4.90)



Heart Disease


(0.51, 4.08)




(0.59, 4.97)



Table 4 Stepwise multivariable logistic regression results of association between physiologic mea- sures, including both lactate level plus SOFA score and in-hospital mortality. Only statisti- cally significant variables were reported in the model.

Odds ratio

95% CI

Arrival SOFA


(1.11, 1.38)

SOFA clearance


(0.72, 0.98)



(0.12, 0.92)

goodness of fit of data. The VIF values were all close to 1.0 (see Table 3), demonstrating no multicollinearity among the independent variables.

In a forward stepwise multivariable logistic regression that included lactate, lactate clearance, SOFA, and SOFA reduction, only SOFA score at arrival (OR 1.24, 95% CI 1.11-1.38) and SOFA score reduction during CCRU stay (OR 0.84, 95% CI 0.72-0.98) was associated with patients’ in-hospital mortality. The only other variable that remained significant was hypertension with an odds ratio of 0.33 (95% CI: 0.12-0.92) (Table 4).

  1. Discussion

Our study demonstrates that early reduction of certain physiologic markers during the acute resuscitation phase of critical illness is associ- ated with better outcomes. Among a group of patients with signs of shock, our study demonstrated that every point of SOFA score reduction during patients’ short stay in the CCRU was associated with reduced in- hospital mortality. However, one of our hypotheses, that lactate clear- ance in this patient population would be associated with in-hospital mortality, was not supported by the study’s findings.

This is the first study to demonstrate a relationship between resusci-

tative efforts, physiologic score improvement, and subsequent mortality outcomes among patients in a dedicated resuscitation unit. These re- sults support prior literature that suggests early and effective resuscita- tion during the Hyperacute phase improved patients’ outcomes. Nguyen et al. showed that patients with septic shock had lower mortality with early and effective resuscitation that started in the ED, and when resus- citation efforts improved patients’ physiologic scores both in the ED and within 24 h of presentation [9]. Our results also help to explain our pre- vious observations that patients from other hospitals who were trans- ferred to the CCRU had improved outcomes when compared with patients who had similar SOFA scores but were delayed in transfer to other traditional Intensive Care Units at our institution [11]. While fur- ther studies are necessary to confirm our previous study, the previous findings are probably due to the fact that patients with Critical illnesses who were expeditiously transferred to the CCRU received early and effective resuscitation.

Lactate clearance has been shown previously to be associated with improved patient outcomes [7,12]. However, our study was not able

to support these findings. Our patient population with high serum lac- tate levels had an average reduction of 1.9 mmol/L, but there was no as- sociation with mortality in our multivariable logistic regression. This discrepancy was likely multifactorial. The amount of lactate clearance during CCRU stay was relatively small compared to the quite elevated lactate on arrival (average clearance was 25% of arrival lactate). This rel- atively small amount of clearance might not have been sufficient to be associated with improved mortality outcomes. Our patient population was heterogeneous and the benefits of lactate clearance may not apply to all Disease states. Furthermore, previous studies used lactate clearance within 12-24 h, as reported by Zhang Z et al., while our study only assessed lactate clearance during patients’ CCRU stay of within 6-8h [12]. Additionally, the mean lactate serum in our patient population was somewhat higher than the population by Scolari et al. (median arrival lactate of 6.1) [4]. Similarly, the range of initial lactate in studies included in Zhang Z et al.’s meta-analysis was from 3 to 6 mmol/L [12].

We observed that the mean reduction of SOFA score during CCRU

stay was only 0.2 points. This finding is probably due to SOFA Score re- duction in some patients being offset by a SOFA Score increase among a subset of CCRU patients who received interventions in the CCRU that in- creased their SOFA score. For example, 26% of patients were intubated in the CCRU, which increases patients’ respiratory SOFA score. Similarly, vasopressor was initiated in up to 12% of patients, which increases pa- tients’ cardiac SOFA score. Despite this effect on the SOFA Score, these early interventions are overall beneficial through improvement of pa- tients’ physiologic support via reduction of hypoxia and hypoperfusion. The effects of these early interventions are supported by previous stud- ies which suggest that early norepinephrine and appropriately early in- tubation are associated with lower mortality rate [13-15]. Although the overall reduction in SOFA score was small, the overall effect of SOFA score reduction during the short CCRU stay was significant. Each one- unit reduction in SOFA score was associated with approximately 16% likelihood of lower mortality during hospital stay. While the effective- ness of the CCRU likely stems from the efforts of a Multidisciplinary team that provides definitive and Longitudinal care for patients from the time when they arrive to the CCRU through their hospital stay, our results provide further supportive evidence for early resuscitation among a population of patients who present with elevated serum lac- tate levels. These results also provide certain prognostic value to suggest who may survive to hospital discharge, although further study with a larger patient population will be needed to confirm the use of early SOFA clearance as a prognostic factor among patients with critical illness.

The 6-bed CCRU was designed as a high throughput resuscitation

unit and its design allows it to provide high care intensity for patients [10,11]. The unit is staffed around the clock by a Critical Care fellowship-trained attending physician and an Advanced Practice Prac- titioner with critical care experience. Furthermore, the CCRU is staffed

by nurses who are required to have at least 3 years of prior ICU experi- ence. The flexible staffing model in the CCRU enables a “very sick” pa- tient in the CCRU to receive clinical attention from both CCRU clinicians and up to 2 or 3 CCRU nurses to provide bed-side care for the patient, until the patient is “stabilized” so that they can be taken to the operating room or to an available bed at an appropriate Inpatient unit. To provide early resuscitation measures, the CCRU utilizes antici- patory approaches such as preparing uncrossed blood products and va- soactive infusion medications to be ready at the bedside, as appropriate, while the patients are in transit, even when the patient is not registered within our institutional electronic medical record (EMR) system [11]. As such, the resources and the design of the CCRU enables it to function dif- ferently from an Emergency Department or a traditional ICU, when pa- tients are required to be physically in the ED or ICU and to have an official medical record number in the EMR.

  1. Limitations

Our study had several limitations. The CCRU experience may not be generalizable as the aforementioned CCRU’s goals and design may not be replicated at another institution. Although the University of Michigan’s Emergency Critical Care Center (EC3) also provides early in- terventions and resuscitation, it was designed to address the institution’s goal to reduce prolongED boarding of critically ill patients of the institution’s ED [16]. Additionally, our patient population is het- erogeneous, and the benefits of lactate clearance or SOFA score reduc- tion might not apply to all disease states, such as patients who have ischemic stroke or spontaneous intracerebral hemorrhage, status epi- lepticus. As such, further studies with larger and more homogeneous patients are needed to confirm our observations. Furthermore, by ex- cluding patients who did not have both serum lactate levels or SOFA score when they left the CCRU, we potentially excluded those who were “very sick” or those “not sick enough”. Patients who were “very sick” may need to go to the operating room or a surgical intervention immediately, before further laboratory assessments were repeated. On the other hand, patients who were “not sick” may not need repeat lab- oratory assessments, therefore, a future study with SOFA score after 24 h of arrival will also be beneficial, although the 24-h SOFA score may not be a reflection of the CCRU’s resuscitation or interventions. Ad- ditionally, patients who were less sick may be more likely to receive in- terventions, such as surgical source control, resulting in improved likelihood of hospital survival. In contrast, patients who were consid- ered “too sick” may not undergo these interventions. A future study with a more balanced group of patients, using either randomization or matching methods, is be needed.

  1. Conclusion

Early intensive resuscitation in the CCRU was associated with clear- ance of patients’ lactate values and, to a lesser extent, reduction in pa- tients’ SOFA score. Although reducing SOFA score during CCRU stay was associated with improved in-hospital mortality, lactate clearance was not. Further studies with a larger and more homogenous patient population are needed to confirm our observations.


No sources of financial support to report.

Credit authorship contribution statement

Taylor Miller: Writing – original draft, Methodology, Formal analy- sis, Data curation, Conceptualization. Nikki Emamian: Writing – review

& editing, Resources, Data curation. Zoe Glick: Data curation. Nelson Chen: Data curation. Tiffany Cao: Data curation. Adelina Buganu: Data curation. Stephanie Cardona: Data curation. William Teeter: Writing – review & editing, Conceptualization. Daniel J. Haase: Writing – review & editing, Conceptualization. Quincy K. Tran: Writing – review & editing, Writing – original draft, Project administration, Methodology, Investigation, Formal analysis, Conceptualization.

Declaration of Competing Interest

The authors have no conflict of interest to report.

Appendix A. Supplementary data

Supplementary data to this article can be found online at https://doi. org/10.1016/j.ajem.2022.07.042.


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