Open Access Original Article

Prediction of Neurological Outcomes in Elderly
Patients With Head Trauma Using the GeriatricTrauma Outcome Score: A Retrospective
Observational Study

Review began 07/15/2024
Review ended 08/08/2024
Published 08/13/2024© Copyright 2024
Iizawa et al. This is an open access article
distributed under the terms of the Creative

Yuta Iizawa 1, 2 , Yosuke Hayashi 1, 2 , Daiki Saito 1, 2, Kengo Kondo 1, 2 , Mana Yamashiro 1, 2,
Rie Kanematsu 1, 2, Kimihito Hirose 1, 2, Michio Nakamura 3, Tadashi Miyazaki 3

Commons Attribution License CC-BY 4.0.,
which permits unrestricted use, distribution,and reproduction in any medium, provided
the original author and source are credited.

1. Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine, Chiba, JPN 2.
Department of Emergency and Critical Care Medicine, Japan Red Cross Narita Hospital, Narita, JPN 3. Department of
Neurosurgery, Japan Red Cross Narita Hospital, Narita, JPN

DOI: 10.7759/cureus.66768

Corresponding author: Yosuke Hayashi, yosukehayashi19851117@gmail.com

Abstract
Introduction
Head trauma in elderly people is a problem in today's aging society. Elderly people are susceptible to headtrauma because of their declining physical function; this tends to be severe. Outcome prediction isimportant in decision-making regarding treatment strategies; however, there is no unified method forpredicting neurological outcomes in elderly patients with head trauma.

Methods
Elderly patients with head trauma admitted to the Japan Red Cross Narita Hospital between January 2019and August 2023 were enrolled in this single-center, retrospective observational study. A favorable
neurological outcome was defined as a cerebral performance category scale of 1 or 2. Multivariate logistic
regression analysis and receiver operating characteristic curve analysis were performed to investigate theassociation between geriatric trauma outcome scores and outcomes and to evaluate the predictive value of
geriatric trauma outcome scores. The primary outcome was a favorable neurological outcome at discharge,
and the secondary outcome was in-hospital mortality.

Results
A total of 313 elderly patients with head trauma were eligible for analysis. Multivariate logistic regression
analysis revealed that the geriatric trauma outcome score was significantly associated with a favorable
neurological outcome at discharge (odds ratio 0.94, P <0.0001). In the receiver operating characteristic curve
analysis, the geriatric trauma outcome score had a good predictive value for favorable neurological outcomesat discharge (area under the receiver operating characteristic curve 0.83).

Conclusions
The geriatric trauma outcome score had good predictive value for favorable neurological outcomes atdischarge in elderly patients with head trauma and has the potential to aid in decision-making regarding
treatment strategies for elderly patients with head trauma.

Categories: Neurosurgery, Emergency Medicine, Trauma
Keywords: cerebral performance category, geriatric trauma outcome score, neurological outcome, outcome
prediction, head trauma, elderly patients

Introduction
Population aging is prevalent in Japan and globally [1]. Trauma is an important issue in today’s aging
society, as the decline in physical function seen in elderly people leads to trauma [2,3]. Once trauma has
occurred, mortality in elderly patients is higher and the ability to perform activities of daily living (ADL) in
survivors is lower [2] than in younger patients. The most common site of injury excluding the extremities ishead trauma in elderly patients [3]. The incidence of head trauma, especially traumatic brain injury, which is
the most severe form of head trauma, is increasing among elderly patients globally [4,5], and the outcomesof head trauma are poorer than those in younger patients [6]. Thus, head trauma in older adults is a major
problem in today's aging society.
Outcome prediction is important in decision-making for treatment strategies; hence, several predictors havebeen reported, such as acute subdural hematoma (A-SDH) [7-9], oral anticoagulants [10-13], Glasgow coma
scale (GCS) [9,14,15], and severity scores [16,17] for patients with head trauma. However, there is no unified

How to cite this article
Iizawa Y, Hayashi Y, Saito D, et al. (August 13, 2024) Prediction of Neurological Outcomes in Elderly Patients With Head Trauma Using theGeriatric Trauma Outcome Score: A Retrospective Observational Study. Cureus 16(8): e66768. DOI 10.7759/cureus.66768

method for predicting neurological outcomes in elderly patients with head trauma.
The injury severity score (ISS) is commonly used for outcome prediction for patients with trauma [18,19].
However, elderly patients with trauma differ from younger patients in that mortality in elderly patients ishigher than that in younger patients, even with similar ISS [20], and the geriatric trauma outcome score(GTOS) was developed to predict mortality in elderly patients with trauma [21]. GTOS was first reported by
Zhao et al. in 2015 and can be calculated at the bedside using only three factors: age, ISS, and transfusion of
packed red blood cells (PRBCs). There have been few reports examining morbidity, but only one report
investigated the association between GTOS and morbidity at discharge in elderly patients with trauma [22].
Whether GTOS is associated with neurological outcomes in elderly patients with head trauma is unclear.
We hypothesized that GTOS could predict neurological outcomes at discharge in elderly patients with headtrauma. To demonstrate this, we analyzed the association between GTOS and neurological outcomes atdischarge in elderly patients with head trauma who were admitted to our hospital.

Materials And Methods
Study setting and patients
This single-center, retrospective observational study was conducted at a tertiary emergency and critical carecenter of Japan Red Cross Narita Hospital, located in an urban area of Japan. The study was conducted fromJanuary 2019 to August 2023. Patients who visited the emergency department (ED) within the study period
were screened for eligibility. We included elderly (≥65 years old) patients who were admitted to our hospitalwith the diagnosis of head trauma. We excluded patients who died in the ER or were diagnosed with achronic subdural hematoma (C-SDH) or nontraumatic hemorrhage. If patients had been admitted multiple
times, only first-admission data were analyzed.
The protocol for this research project was approved by a suitably constituted Ethics Committee of theinstitution and it conforms to the provisions of the Declaration of Helsinki (Committee of the Japan Red
Cross Narita Hospital Certified Clinical Research Review Board, Approval No. 884-01). The requirement for
written informed consent was waived by the Review Board because of the retrospective study design, in
conformity with the Ethical Guidelines for Medical and Health Research Involving Human Subjects inJapan. Opt-outs for the study were posted on hospital websites.

Data collection and definition
Patient data were retrospectively reviewed and extracted from medical records. The collected data for
analysis included patient characteristics (age, sex, mechanism of injury (traffic accident, fall, and others),
and oral anticoagulants), type of cerebral lesions (traumatic subarachnoid hemorrhage (SAH), acute SDH (ASDH), acute epidural hematoma (A-EDH), mixed lesions, and other hemorrhage, contusions, concussion,and others), severity scores (abbreviated injury score (AIS), ISS, and GTOS), and outcomes (mortality, lengthof hospital stay, and cerebral performance category (CPC) scale [23] and Glasgow outcome scale (GOS)[24] at discharge). The injury type was diagnosed by neurosurgeons during hospitalization and extracted
based on the International Classification of Diseases, 10th Revision. A favorable neurological outcome atdischarge was defined as a CPC score of 1 or 2. For the calculation of ISS, the six body regions (head andneck, face, chest, abdomen, extremities, and external) are assigned an AIS of 0 to 5 depending on theseverity of the injury. AIS 0 means uninjured and 5 means maximally injured while still being compatible
with life. The ISS of a patient is calculated from the sum of the squares of the three worst AISs [18]. The
GTOS was calculated using the following formula [21]:GTOS = Age + (2.5*ISS) + 22 (if given PRBCs within 24 h of admission)
Table 1 lists the CPC scores.

2024 Iizawa et al. Cureus 16(8): e66768. DOI 10.7759/cureus.66768

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ScoreGood Cerebral
1

Performance(Normal Life)

Conscious, alert, able to work and lead a normal life. May have minor psychological or neurologic deficits (milddysphasia, non-incapacitating hemiparesis, or minor cranial nerve abnormalities).

2

Moderate
Cerebral
Disability(Disabled but
Independent)

Conscious. Sufficient cerebral function for part-time work in a sheltered environment or independent activities
of daily life (dress, travel by public transportation, food preparation). May have hemiplegia, seizures, ataxia,
dysarthria, dysphasia, or permanent memory or mental changes.

3

Severe Cerebral
Disability(Conscious but
Disabled and
Dependent)

Conscious; dependent on others for daily support (in an institution or at home with exceptional family effort).
Has at least limited cognition. This category includes a wide range of cerebral abnormalities, from patients who
are ambulatory but have severe memory disturbances or dementia precluding independent existence to those
who are paralyzed and can communicate only with their eyes, as in the locked-in syndrome.

4

Coma/Vegetative
State(Unconscious)

Unconscious, unaware of surroundings, no cognition. No verbal or psychological interaction with theenvironment.

5

Brain Death(Certified brain
dead or dead bytraditional
criteria)

Certified brain dead or dead by traditional criteria.

TABLE 1: Cerebral performance category scores

Statistical analysis
The primary outcome was a favorable neurological outcome (CPC ≤2) at discharge and the secondary
outcome was in-hospital mortality. To clarify the association between the GTOS and outcomes, we
performed univariate and multivariate logistic regression analyses, calculated the odds ratio (OR) and 95%
confidence interval (CI), and compared them with the ISS and AIS scores of the head and neck. Multivariate
analysis was adjusted by sex, mechanism of injury (traffic accident, fall, and others), type of cerebral lesions(traumatic SAH, A-SDH, A-EDH, mixed lesions, other hemorrhage, contusions, concussion, and others), andoral anticoagulants.
Model performance was measured using receiver operating characteristic curve (ROC) analysis, and the area
under the ROC (AUROC) was evaluated. The cut-off value of the GTOS was calculated using the Youden
index.
Moreover, we performed the above analysis using GOS, which is used as another outcome scale in previous
studies [25], as good recovery (GOS=5) is a favorable neurological outcome. Furthermore, we performed asubgroup analysis according to the severity of head trauma. Patients were divided based on their AIS into asevere head trauma group (AIS=1,2) and a non-severe head trauma group (AIS ≥3).
Data are expressed as medians and interquartile ranges for continuous variables and absolute numbers (%)
for categorical variables. The AUROC was expressed with CI. Statistical significance was set
at P <0.05. Analyses were performed using the IBM SPSS Statistics for Macintosh, Version 26.0.0. (Armonk,
NY: IBM Corp).

Results
Baseline characteristics and clinical outcomes
A total of 491 elderly patients with head trauma were screened. Of these, 313 patients were analyzed after
excluding 5 patients who died in the ED, 7 who had been admitted multiple times, 165 with a diagnosis of CSDH, and 1 with a non-traumatic disease (Figure 1).

2024 Iizawa et al. Cureus 16(8): e66768. DOI 10.7759/cureus.66768

3 of 11FIGURE 1: Patient flowchart
ED, emergency department; C-SDH, chronic subdural hematoma; CPC, cerebral performance category.

In total, 154 patients had a favorable neurological outcome at discharge (65 patients were CPC 1 and 89
patients were CPC 2) and were classified into the CPC ≤2 group. In contrast, 159 patients had an unfavorable
outcome at discharge (68 patients were CPC 3, 46 patients were CPC 4, and 45 patients were CPC 5) and into
the CPC >2 group. The CPC ≤2 group had a significantly lower age, a higher percentage of male patients, andfalls as a mechanism of injury than the CPC >2 group. As the type of injury, the CPC >2 group had
significantly higher traumatic SAH and concussion and lower A-SDH and mixed hemorrhage. AIS points ofhead and neck, ISS, and GTOS in the CPC ≤2 group were significantly lower in the CPC ≤2 group, and thelength of hospital stay was significantly shorter in the CPC ≤2 group (Table 2). Patients who died wereclassified into the CPC >2 group according to the definition of CPC. In-hospital mortality was 28.3% in
the CPC >2 group.

CPC ≤2 (n = 154)

CPC >2 (n = 159)

P-value

78.0 (72.0–82.0)

82.0 (76.0–87.0)<0.001Pre-old, n (%)

57 (37.0)

32 (20.1)<0.01

Old, n (%)

69 (44.8)

65 (40.9)

0.48

Age, years
Age group2024 Iizawa et al. Cureus 16(8): e66768. DOI 10.7759/cureus.66768

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Oldest-old, n (%)

28 (18.2)

62 (39.0)<0.001

Male sex, n (%)

81 (52.6)

112 (70.4)<0.01

Traffic accident, n (%)

22 (14.3)

15 (9.4)

0.19

Fall, n (%)

97 (61.0)

116 (75.3)<0.01

Unknown, n (%)

16 (10.4)

47 (29.6)<0.001

Oral antithrombotic, n (%)

50 (32.5)

48 (30.2)

0.66

Traumatic SAH, n (%)

48 (31.2)

28 (17.6)<0.01

A-SDH, n (%)

35 (22.7)

72 (45.3)<0.001

A-EDH, n (%)

7 (4.5)

11 (6.9)

0.37

Mixed hemorrhage

8 (5.2)20 (12.6)<0.05

Other hemorrhage

5 (3.2)2 (1.3)0.24

Contusion

15 (9.7)

23 (14.5)

0.20

Concussion

29 (18.8)

2 (1.3)<0.001Other

7 (4.5)1 (0.6)<0.05

Head and neck

2.0 (2.0–3.0)

4.0 (3.0–5.0)<0.001Face

0.0 (0.0–0.0)

0.0 (0.0–0.0)

0.28

Chest

0.0 (0.0–0.0)

0.0 (0.0–0.0)

0.85

Abdomen

0.0 (0.0–0.0)

0.0 (0.0–0.0)

0.98

Extremities

0.0 (0.0–0.0)

0.0 (0.0–0.0)

0.10

External

0.0 (0.0–1.0)

0.0 (0.0–0.0)<0.05

Injury severity score

8.0 (4.0–9.0)

17.0 (9.0–25.0)<0.001

GTOS

94.8 (85.6–106.3)

126.0 (107.5–145.0)<0.001

Transfusion of PRBCs, n (%)

1 (0.6)

1 (0.6)

0.98

Mechanism of injury

Type of injury

Abbreviated injury score

OutcomeMortality, %28.3

Length of hospital stay, days

5.2 (2.3–9.0)

17.8 (3.9–34.0)<0.001TABLE 2: Baseline characteristics and outcomes of the CPC ≤2 group and the CPC >2 group
CPC, cerebral performance category; SAH, subarachnoid hemorrhage; A-SDH, acute subdural hematoma; A-EDH, acute epidural hematoma; GTOS,
geriatric trauma outcome score; PRBCs, packed red blood cells
Data are presented as median and interquartile range for continuous variables.
P-values were calculated using the Mann-Whitney U test.

The association between a favorable neurological outcome and the
GTOS
The univariate logistic regression analysis revealed the association between a favorable neurological2024 Iizawa et al. Cureus 16(8): e66768. DOI 10.7759/cureus.66768

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outcome at discharge and scoring systems (GTOS, OR 0.94, CI 0.93-0.96, P <0.001; ISS, OR 0.86, CI 0.830.89, P <0.001; AIS points of the head and neck, OR 0.37, CI 0.29-0.46) (Table 3). In the multivariate analysis
adjusted by sex, mechanism of injury, type of cerebral lesions, and oral anticoagulants, the GTOS wassignificantly associated with a favorable neurological outcome at discharge (OR 0.94, CI 0.92-0.96, P <0.001).

Odds ratio

P-valueGTOS

0.94 (0.93–0.96)<0.001ISS

0.86 (0.83–0.89)<0.001

AIS (head and neck) ≧4

0.37 (0.29–0.46)<0.001GTOS

1.07 (1.05–1.09)<0.001ISS

1.25 (1.17–1.33)<0.001GTOS

0.94 (0.92–0.96)<0.001ISS

0.86 (0.81–0.90)<0.001

AIS (head and neck) ≧4

0.32 (0.22–0.47)<0.001GTOS

1.08 (1.05–1.11)<0.001ISS

1.31 (1.19–1.43)<0.001

Univariate
CPC ≤2 at discharge

Mortality

Multivariate
CPC ≤2 at discharge

Mortality

TABLE 3: Univariate and multivariate analysis for the association between outcomes at discharge
and the GTOS, ISS, and AIS in elderly patients
Multivariate analysis was adjusted by sex, mechanism of injury (traffic accident, fall, and others), type of cerebral lesions (traumatic subarachnoid
hemorrhage, acute subdural hematoma, acute epidural hematoma, mixed lesions, other hemorrhage, contusions, concussion, and others), and oral
anticoagulants.
GTOS, geriatric trauma outcome score; ISS, injury severity score; AIS, abbreviated injury scale; CPC, cerebral performance category

In the ROC analysis, GTOS had the highest AUROC (GTOS, AUROC 0.83, CI 0.78-0.87; ISS, AUROC 0.80, CI
0.75-0.85; AIS points of head and neck, AUROC 0.75, CI 0.69-0.81) (Figure 2A). The cutoff value of the GTOS
as a predictor of a favorable outcome at discharge was 107.5 according to the Youden index with a sensitivityof 0.76 and a specificity of 0.77.

2024 Iizawa et al. Cureus 16(8): e66768. DOI 10.7759/cureus.66768

6 of 11FIGURE 2: Receiver operation characteristic analysis of outcomes
A. CPC ≤2 at discharge; B. Mortality
AUROC, area under the receiver operation characteristic curve; CI, confidence interval; GTOS, geriatric trauma
outcome score; ISS, injury severity score; AIS, abbreviated injury scale; CPC, cerebral performance category

Furthermore, even using the GOS as a neurological outcome at discharge, GTOS had the highest AUROC(GTOS, AUROC 0.79, CI 0.73-0.84; ISS, AUROC 0.75, CI 0.70-0.81; AIS points of head and neck, AUROC 0.77,
CI 0.72-0.83) (Figure 3).

2024 Iizawa et al. Cureus 16(8): e66768. DOI 10.7759/cureus.66768

7 of 11FIGURE 3: Receiver operation characteristic analysis of Glasgow
Outcome Scale.
AUROC, area under the receiver operation characteristic curve; CI, confidence interval; GTOS, geriatric trauma
outcome score; ISS, injury severity score; AIS, abbreviated injury scale

The association between mortality and the GTOS
The univariate logistic regression analysis revealed the association between mortality and severity scores(GTOS, OR 1.07, CI 1.05-1.09, P <0.001; ISS, OR 1.25, CI 1.17-1.33, P <0.0001) (Table 3). In the multivariate
analysis, the GTOS was significantly associated with mortality (OR 1.08, CI 1.05-1.11, P <0.001). In the ROC
analysis, the GTOS and ISS had almost equal AUROC (GTOS, AUROC 0.89, CI 0.85-0.94; ISS, AUROC 0.89, CI
0.84-0.94) (Figure 2B).

Subgroup analysis according to the severity of head trauma
Patients were divided into a severe head trauma group (n=197) and a non-severe head trauma group(n=116). In the subgroup analysis, the GTOS was significantly associated with a favorable neurologicaloutcome at discharge defined as CPC ≤2 in both the severe (univariate, OR 0.95, CI 0.93-0.97, P <0.001;
multivariate, OR 0.94, CI 0.92-0.96, P <0.001) and non-severe (univariate, OR 0.94, CI 0.90-0.99, P=0.015;
multivariate, OR 0.95, CI 0.91-0.99, P=0.046) subgroups. In the ROC analysis, the GTOS had an acceptableperformance in the severe group (AUROC 0.77, CI 0.70-0.85) and poor AUROC in the non-severegroup (AUROC 0.67, CI 0.55-0.79).

Discussion
The present study demonstrated that a higher GTOS was associated with worse neurological outcomes atdischarge in elderly patients with head trauma. Furthermore, the GTOS had a high predictive value forneurological outcomes at discharge, which was higher than the ISS and AIS scores of the head and neck. The
GTOS also had a high predictive value for in-hospital mortality, which was almost equal to the ISS. In
addition, the subgroup analysis revealed that the GTOS was significantly associated with a favorable
neurological outcome at discharge in both the severe and non-severe subgroups, and had acceptable AUROC
in the severe subgroup. Therefore, the GTOS has the potential to be a tool for the outcome prediction
precision of elderly patients with head trauma and can be a useful scoring system for decision-making. The
valid cutoff values should be clarified through a multicenter prospective study in the future.
In today's aging population, it is important to recognize the characteristics of elderly people who are2024 Iizawa et al. Cureus 16(8): e66768. DOI 10.7759/cureus.66768

8 of 11susceptible to trauma owing to a decline in various physical functions, such as the visual andmusculoskeletal systems, and have slower reflexes and reaction times to avoid trauma [2,3]. In addition,
having comorbidity and medication such as oral anticoagulants increases the risks of trauma [12,13,26,27].
In this study, the most frequent mechanism of injury was falling, probably due to a decline in physicalfunction, and approximately one-third of patients were taking oral anticoagulants. These effects in elderly
patients with trauma tend to be more severe, elderly patients with trauma have higher mortality rates than
younger patients, even those with similar ISS [20]. Therefore, predicting the outcomes is important inelderly patients with trauma. This study focused on the GTOS, which was developed to predict mortality inelderly patients, and showed that it had a good predictive value for outcomes, including neurologicaloutcomes, in elderly patients with head trauma. Additionally, the subgroup analysis showed a significant
association between the GTOS and a favorable neurological outcome, and the GTOS had an acceptable
AUROC in the severe head trauma group. In the non-severe subgroup, the GTOS was still significantly
associated with a favorable neurological outcome; however, it had a poor predictive value. These findings
suggest that the GTOS may be more beneficial in predicting the outcome of patients with severe headtrauma.
Various risk factors of mortality and morbidity in patients with head trauma have been reported. In terms of
cerebral lesions, A-SDH is known to be associated with a poor prognosis due to a high tendency to cause
serious brain damage [7-9]. From the perspective of medication, oral anticoagulants are a risk factor for poor
prognosis due to worsening bleeding [10-13]. In addition, some studies have shown that the GCS on
admission is associated with mortality [14,15] and morbidity [9]. Cerebral injury is not only a brain disease,patients with brain injury may develop other organ failure even if they have no systemic diseases orinfection [28]. In terms of a physiologic point of view, severity scores, such as the APACHE II score [17] or
SOFA score [16], were associated with mortality. However, there are currently no established outcome
prediction systems. In this study, GTOS showed a high predictive AUROC value of 0.83 for predicting afavorable neurological outcome and an AUROC of 0.89 for mortality. This study is valuable in revealing that
the GTOS is useful for predicting outcomes in elderly patients with head trauma.
This study has several limitations. First, there may have been a selection bias because this was a singlecenter retrospective study. Numerous factors would affect the prognosis of patients with head trauma andthat makes it incredibly difficult to predict outcomes of patients with head trauma. We performed themultivariate analysis adjusted sex, mechanism of injury, type of cerebral lesions, and oral anticoagulants;
however, there were still a lot of factors that should be considered such as the volume of hematomas,
prehospital process, and time course of physical rehabilitation. These were not able to be extracted
accurately from the electronic medical record. The results of this study should be validated in a prospective
multicenter study, including the determination of the appropriate cutoff value of GTOS for decision-making
regarding treatment strategies. Second, our study patients had a few serious injuries to other parts of the
body. It is well known that there is a relationship between head trauma and torso trauma, which can lead toserious conditions. Head trauma can cause severe hyperfibrinolysis [29,30], which leads to severe torso
hemorrhage in patients with multiple trauma. Patients with severe multiple trauma, including head trauma,
are an important research target and should be validated in these patient groups in the future. Third, few
patients received PRBC transfusions. The GTOS is composed of three factors: age, ISS, and transfusion of
PRBC; however, we could not investigate the effect of transfusion of PRBC on outcome prediction. This
could be attributed to the small number of patients with severe multiple trauma, which should be validated
in the future. Fourth, we did not consider cognitive impairment prior to being admitted to our hospital
because of the lack of exact information from medical records. Age in the CPC >2 group was significantly
higher, so they might have a higher previous impairment before injury. It may cause a bias.

Conclusions
This is a single-center retrospective study investigating the prediction of neurologic outcomes at discharge
in elderly patients with head trauma for which there have been no unified methods. This study revealed that
the GTOS has good predictive value for favorable neurological outcomes at discharge in elderly patients withhead trauma.
The incidence of head trauma is increasing in elderly patients globally and its severity is higher than in theyounger. Improving the outcome of head trauma in elderly patients is a major challenge in today's aging
society. The GTOS has the potential to be useful for predicting outcomes and aids in decision-making
regarding treatment strategies for elderly patients with head trauma. As for future research, it is necessary
to reveal appropriate cutoff values for the prediction in a multicenter prospective study and to establish
treatment strategies based on GTOS for improving the neurological outcomes of head trauma in elderly
patients.

Additional Information
Author Contributions
All authors have reviewed the final version to be published and agreed to be accountable for all aspects of thework.

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Concept and design: Yosuke Hayashi, Daiki Saito
Acquisition, analysis, or interpretation of data: Yosuke Hayashi, Yuta Iizawa, Kengo Kondo, Mana
Yamashiro, Rie Kanematsu, Kimihito Hirose, Michio Nakamura, Tadashi Miyazaki
Drafting of the manuscript: Yosuke Hayashi, Yuta Iizawa
Critical review of the manuscript for important intellectual content: Daiki Saito, Kengo Kondo, Mana
Yamashiro, Rie Kanematsu, Kimihito Hirose, Michio Nakamura, Tadashi Miyazaki
Supervision: Daiki Saito, Michio Nakamura

Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Committee of the JapanRed Cross Narita Hospital Certified Clinical Research Review Board issued approval 884-01. The protocol forthis research project has been approved by a suitably constituted Ethics Committee of the institution and it
conforms to the provisions of the Declaration of Helsinki. Committee of the Japan Red Cross Narita Hospital
Certified Clinical Research Review Board, Approval No. 884-01. The requirement for written informed
consent was waived by the Review Board because of the retrospective study design, in conformity with the
Ethical Guidelines for Medical and Health Research Involving Human Subjects in Japan. Opt-outs for the
study were posted on hospital websites. This trial was retrospectively registered with the University Hospital
Medical Information Clinical Trials Registry (No. UMIN000053468. Registered January 31, 2024). Animal
subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts ofinterest: In compliance with the ICMJE uniform disclosure form, all authors declare the following:
Payment/services info: All authors have declared that no financial support was received from anyorganization for the submitted work. Financial relationships: All authors have declared that they have nofinancial relationships at present or within the previous three years with any organizations that might havean interest in the submitted work. Other relationships: All authors have declared that there are no otherrelationships or activities that could appear to have influenced the submitted work.

Acknowledgements
We would like to thank Honyaku Center Inc. for English language editing.

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