Abstract
Purpose
The Coronavirus Disease 2019 (COVID-19) pandemic delayed elective procedures such as total joint arthroplasty. As surgical volumes return to prepandemic levels, understanding the implications of COVID-19 becomes imperative. This study explored the effects of COVID-19 on the short-term outcomes of hip arthroplasty.
Methods
This multicenter, retrospective, case–control study included patients who had undergone hip arthroplasty between 2020 and 2022. Propensity score matching (PSM) was performed to compare demographic characteristics, primary outcomes, and secondary outcomes between patients with a history of COVID-19 (COVID-19 cohort) and those without it (control cohort). The primary outcomes were surgical site infection, periprosthetic joint infection (PJI), dislocation, prosthesis loosening, deep vein thrombosis, and pulmonary embolism. The secondary outcomes were intraoperative blood loss, nerve injury, renal injury, urinary tract infection (UTI), pneumonia, and acute coronary syndrome.
Results
The COVID-19 and control cohorts comprised 153 and 4925 patients, respectively. After PSM, significant between-cohort differences were observed in the incidence of pneumonia (p < 0.001) and UTI (p = 0.0424). The odds ratio for PJI was 1.62, which is not significant (p = 0.3238) but the culture-negativity rate is higher in the COVID-19 cohort (25%).
Conclusion
Our findings suggest that COVID-19 only elevated risks of postoperative pneumonia and UTI after hip arthroplasty. This disease significantly increases the risk of postoperative pneumonia but not of 90-day mortality or any major perioperative complication. On the other hand, PJI still remains a concern because its treatment is challenging owing to its culture-negativity, often necessitating the Girdlestone procedure.
Keywords: COVID-19, Culture-negative periprosthetic joint infection, Hip arthroplasty, Postoperative pneumonia
Introduction
The Coronavirus Disease 2019 (COVID-19) pandemic had resulted in the postponement of elective procedures, such as total joint arthroplasty. After 2022, surgical volumes around the globe returned to prepandemic levels. Given the momentous impact of the COVID-19 pandemic, we must understand COVID-19’s implications on perioperative outcomes, particularly those of total joint arthroplasty [1–5].
COVID-19 has been reported to be associated with postoperative mortality in patients undergoing orthopedic and trauma surgery [6]. This disease may activate systemic coagulation and induce excess inflammation, leading to thrombotic disease and cardiopulmonary complications [7–10]. However, studies have reported inconsistent findings, with some reporting that COVID-19 does not affect the risks of venous thromboembolism (VTE), overall mortality, or readmission [11, 12]. Thus we wondering about whether hip arthroplasty procedure is safe to be performed with a recent history of COVID-19 infection because we do not use anti-coagulant in total hip arthroplasty.
In this study, we tried to review and investigated the effects of COVID-19 on the short-term outcomes of hip arthroplasty. Specifically, we compared not only the orthopedic related outcome such as risks of hip dislocation, revision surgery, periprosthetic joint infection (PJI), VTE, but also nonorthopedic complications between patients with a history of COVID-19 and those without it [12]. We hypothesized that a history of COVID-19 is associated with increased risks of PJI, VTE, and cardiopulmonary complications.
Methods
This multicenter, retrospective, case–control study included patients who had undergone hip arthroplasty—total hip arthroplasty, bipolar hemiarthroplasty, or revision total hip arthroplasty—at Chang Gung Memorial Hospital in Keelung, Linko, Chia-Yi, and Kaosiung branch between January 2020 and September 2022 and were followed for at least 1 year. Eligible patients were identified from the hospital’s research database. The included patients were divided into COVID-19 and control cohorts, which comprised patients with and without a history of a COVID-19, respectively. We excluded patients with a history of malignant neoplasm, rheumatoid arthritis, pyogenic arthritis, or PJI. Figure 1 depicts the flow of patient enrollment according to the inclusion criteria. This study was approved by the Institutional Review Board of Chang Gung Memorial Hospital.
Fig. 1.
Flowchart of patient enrollment. The inclusion criteria and exclusion criteria were demonstrated and also the final enrollment for analysis
From the patients’ medical records, we collected data on demographic characteristics, surgical intervention, bacterial diversity in surgical samples, albumin levels, initial C-reactive protein levels, comorbidities, complications, and treatment outcomes. Information on comorbidity burden was obtained on the basis of the Charlson Comorbidity Index (CCI) scores. We performed 1:4 propensity score matching (PSM) to compare the COVID-19 and control cohorts in terms of the rates of short-term postoperative outcomes and complications. The primary outcomes were surgical site infection, PJI, hip dislocation, prosthesis loosening, deep vein thrombosis, and pulmonary embolism. The secondary outcomes were intraoperative blood loss, nerve injury, renal injury, urinary tract infection (UTI), pneumonia, and acute coronary syndrome.
Statistical analyses were performed using SAS (version 9.4; SAS Institute, Cary, NC, USA). Continuous variables were compared using the Student t test, whereas categorical variables were compared using the chi-square or Fisher exact test. Logistic regression was performed to estimate the odds ratios (ORs). Statistical significance was set at p < 0.05.
Results
A total of 6007 patients underwent hip arthroplasty between January 2020 and September 2022. After excluding ineligible patients, we included 5078 patients in the final analysis. Among these patients, 153 were in the COVID-19 cohort and 4925 were in the control cohort. The demographic characteristics, comorbidities, and orthopedic and nonorthopedic outcomes of the two cohorts before PSM are summarized in Table 1. Significant between-group differences were noted in age, albumin level, renal function, CCI score, hypertension, diabetes mellitus, liver disease, chronic obstructive pulmonary disease, and cardiovascular disease. After PSM by CCI scores, the COVID-19 cohort had a significantly higher prevalence of chronic obstructive pulmonary disease and hepatitis C but a lower level of albumin than did the control cohort (Table 2). Among the 153 patients in the COVID-19 cohort, 35 had received a COVID-19 diagnosis before or on the day of arthroplasty surgery; only three patients required emergency surgery.
Table 1.
Demographic characteristics of the COVID-19 and control cohorts before propensity score matching
| Variables | Patients with Covid-19 n = 153 |
Patients without Covid-19 n = 4925 |
p-value |
|---|---|---|---|
| Basic data | |||
| Male | 61(39.87) | 2040(41.45) | 0.6965 |
| Age (year), mean(SD) | 68.88 ± 16.03 | 66.03 ± 14.95 | 0.0207 |
| Body mass index (kg/m2), mean(SD) | 24.62 ± 4.60 | 25.11 ± 4.50 | 0.2010 |
| Albumin level (g/dL), mean(SD) | 3.66 ± 0.69 | 3.85 ± 0.67 | 0.0058 |
| Creatinine (mg/dL), mean(SD) | 1.42 ± 1.80 | 1.06 ± 1.21 | 0.0179 |
| CRP (mg/L), mean(SD) | 22.90 ± 48.78 | 18.42 ± 42.98 | 0.2788 |
| eGFR (mL/min/1.73m2), mean(SD) | 79.25 ± 41.11 | 85.59 ± 37.27 | 0.0426 |
| Underlying disease | |||
| Charlson comorbidity index, mean(SD) | 1.88 ± 2.06 | 1.11 ± 1.67 | < 0.0001 |
| Hypertension | 86(56.21) | 2284(46.38) | 0.0163 |
| Diabetes | 49(32.03) | 1075(21.83) | 0.0028 |
| Liver disease | 11(7.19) | 136(2.76) | 0.0045a |
| HCV carrier (%) | 11(7.19) | 85(1.73) | 0.0001a |
| HBV carrier (%) | 10(6.54) | 150(3.05) | 0.0288a |
| COPD | 26(16.99) | 317(6.44) | < 0.0001 |
| Renal insufficiency | 32(20.92) | 510(10.36) | < 0.0001 |
| CV disease | |||
| AF(%) | 12(7.84) | 147(2.98) | 0.0028a |
| CAD (%) | 25(16.34) | 419(8.51) | 0.0007 |
| Surgery related variables | |||
| Operation time(min), mean(SD) | 120.42 ± 49.57 | 116.56 ± 58.13 | 0.3575 |
| Blood loss(mL), mean(SD) | 313.24 ± 258.51 | 337.34 ± 319.29 | 0.2614 |
| Procedures | |||
| Procedures(Revision, DAIR, Girdlestone) | 9(5.88) | 144(2.92) | 0.0491a |
| Time from operation to infection (day), Mean (SD) | 104.67 ± 111.84 | 192.54 ± 181.14 | 0.2375 |
| Revision total hip arthroplasty | 4(2.61) | 106(2.15) | 0.5742a |
| DAIR procedure | 2(1.31) | 11(0.43) | 0.0566a |
| Girdlestone procedure | 3(1.96) | 27(0.55) | 0.0602a |
SD, standard deviation; eGFR, estimated Glomerular filtration rate; HCV, hepatitis C virus; HBV, hepatitis B virus; COPD, chronic obstructive pulmonary disease; CV, cardiovascular; AF, atrial fibrillation; CAD, coronary artery disease; DAIR, debridement antibiotics and implant retention
aFisher’s exact test
Table 2.
Demographic characteristics of the COVID-19 and control cohorts after propensity score matching (1:4)
| Variables | Patients with Covid-19 n = 153 |
Patients without Covid-19 n = 612 |
p-value |
|---|---|---|---|
| Basic data | Basic data | ||
| Male | 61(39.87) | 261(42.65) | 0.5336 |
| Age (year), mean(SD) | 68.88 ± 16.03 | 67.96 ± 14.10 | 0.5165 |
| Body mass index (kg/m2), mean(SD) | 24.62 ± 4.60 | 25.02 ± 4.53 | 0.3452 |
| Albumin level (g/dL), mean(SD) | 3.66 ± 0.69 | 3.84 ± 0.67 | 0.0279 |
| Creatinine (mg/dL), mean(SD) | 1.42 ± 1.80 | 1.27 ± 1.54 | 0.383 |
| CRP (mg/L), mean(SD) | 22.90 ± 48.78 | 25.67 ± 49.76 | 0.5585 |
| eGFR (mL/min/1.73m2), mean(SD) | 79.25 ± 41.11 | 79.54 ± 39.50 | 0.9384 |
| Underlying disease | Underlying disease | ||
| Charlson comorbidity index, mean(SD) | 1.88 ± 2.06 | 1.88 ± 2.06 | 1 |
| Hypertension | 86(56.21) | 333(54.41) | 0.6895 |
| Diabetes | 49(32.03) | 201(32.84) | 0.8472 |
| Liver disease | 11(7.19) | 30(4.90) | 0.2611 |
| HCV carrier (%) | 11(7.19) | 14(2.29) | 0.0023 |
| HBV carrier (%) | 10(6.54) | 23(3.76) | 0.1304 |
| COPD | 26(16.99) | 63(10.29) | 0.0208 |
| Renal insufficiency | 32(20.92) | 115(18.79) | 0.5509 |
| CV disease | |||
| AF(%) | 12(7.84) | 30(4.90) | 0.1531 |
| CAD (%) | 25(16.34) | 83(13.56) | 0.3775 |
| Surgery related variables | Surgery related variables | ||
| Operation time(min), mean(SD) | 120.42 ± 49.57 | 117.88 ± 53.12 | 0.5991 |
| Blood loss(mL), mean(SD) | 313.24 ± 258.51 | 309.5 ± 276.29 | 0.8799 |
| Procedures | |||
| Procedures(Revision, DAIR, Girdlestone) | 9(5.88) | 23(3.76) | 0.2584a |
| Time from operation to infection, Mean (SD) | 104.67 ± 111.84 | 181.33 ± 124.52 | 0.3827 |
| Revision total hip arthroplasty | 4(2.61) | 21(3.43) | 0.8007a |
| DAIR procedure | 2(1.31) | 1(0.16) | 0.1036a |
| Girdlestone procedure | 3(1.96) | 1(0.16) | 0.0268a |
aFisher’s exact test
Regarding postoperative complications, significant between-cohort differences were observed in the rates of PJI, pulmonary embolism, acute kidney injury, pneumonia, and UTI (Table 3). However, after PSM by CCI scores, no significant between-cohort difference was noted in the rates of the aforementioned complications, except for the rates of pneumonia (p < 0.001), UTI (p = 0.0424), and the Girdlestone procedure (p = 0.0268; Table 2). Univariate logistic regression revealed that compared with the control cohort, the COVID-19 cohort had significantly elevated risks of PJI (OR: 2.5; 95% confidence interval [CI]: 1.07–5.84), pulmonary embolism (OR: 7.23; 95% CI: 1.55–33.77), acute kidney injury (OR: 2.61; 95% CI: 1.19–5.72), pneumonia (OR: 5.92; 95% CI: 3.72–9.43), and UTI (OR: 2.62; 95% CI: 1.68–4.07), respectively. Although the rate of hip dislocation did not differ significantly between the two cohorts (p = 0.1016), its risk was higher in the COVID-19 cohort than in the control cohort (OR: 2.16; 95% CI: 0.86–5.41; Table 4). Multivariate logistic regression revealed significant between-cohort differences in the risks of pneumonia (OR: 3.49; 95% CI: 1.98–6.14) and UTI (OR: 1.67; 95% CI: 1.01–2.76).
Table 3.
Perioperative complications
| Before PSM | After PSM(1:4) | |||||
|---|---|---|---|---|---|---|
| Variables |
Patients with Covid-19
n = 153 |
Patients without Covid-19
n = 4925 |
p-value |
Patients with Covid-19
n = 153 |
Patients without Covid-19
n = 612 |
p-value |
| Superficial surgical site infection | 2(1.31) | 25(0.51) | 0.1948a | 2(1.31) | 4(0.65) | 0.3446a |
| Prosthetic joint infection | 6(3.92) | 79(1.60) | 0.0422a | 6(3.92) | 15(2.45) | 0.4032a |
| Deep vein thrombosis | 1(0.65) | 25(0.51) | 0.5495a | 1(0.65) | 5(0.82) | 1a |
| Pulmonary embolism | 2(1.31) | 9(0.18) | 0.0415a | 2(1.31) | 2(0.33) | 0.1804a |
| Acute kidney injury | 7(4.58) | 89(1.81) | 0.0250a | 7(4.58) | 16(2.61) | 0.1943a |
| Ischemic heart | 2(1.31) | 41(0.83) | 0.3736a | 2(1.31) | 8(1.31) | 1a |
| Pneumonia | 24(15.69) | 150(3.05) | < 0.0001 | 24(15.69) | 31(5.07) | < 0.0001 |
| Urinary tract infection | 25(16.34) | 342(6.94) | < 0.0001 | 25(16.34) | 64(10.46) | 0.0424 |
| Nerve injury | 0 | 3(0.06) | 1a | 0 | 0 | NA |
| Dislocation | 5(3.27) | 76(1.54) | 0.0963a | 5(3.27) | 13(2.12) | 0.3785a |
| Prosthesis loosening | 11(7.19) | 270(5.48) | 0.3630 | 11(7.19) | 39(6.37) | 0.7153a |
PSM, propensity score matching; NA, not applicable; aFisher’s exact test
Table 4.
Odd ratios for perioperative complications
| Univariate Logistic Regression | ||
| Complications | OR(95% CI) | p-value |
| Superficial surgical site infection | 2.60(0.61–11.06) | 0.1970 |
| Prosthetic joint infection | 2.50(1.07–5.84) | 0.0335 |
| Deep vein thrombosis | 1.29(0.17–9.58) | 0.8033 |
| Pulmonary embolism | 7.23(1.55–33.77) | 0.0118 |
| Acute kidney injury | 2.61(1.19–5.72) | 0.0171 |
| Ischemic heart | 1.58(0.38–6.58) | 0.5315 |
| Pneumonia | 5.92(3.72–9.43) | < 0.0001 |
| Urinary tract infection | 2.62(1.68–4.07) | < 0.0001 |
| Nerve injury | NA | NA |
| Dislocation | 2.16(0.86–5.41) | 0.1016 |
| Prosthesis loosening | 1.33(0.72–2.50) | 0.3636 |
| Multivariate Logistic Regression | ||
| Complications | OR(95% CI) | p-value |
| Superficial surgical site infection | 2.01(0.37–11.10) | 0.4216 |
| Prosthetic joint infection | 1.62(0.62–4.26) | 0.3238 |
| Deep vein thrombosis | 0.80(0.09–6.89) | 0.838 |
| Pulmonary embolism | 4.04(0.57–28.91) | 0.1644 |
| Acute kidney injury | 1.79(0.72–4.42) | 0.2098 |
| Ischemic heart | 1.00(0.21–4.76) | 1 |
| Pneumonia | 3.49(1.98–6.14) | < 0.0001 |
| Urinary tract infection | 1.67(1.01–2.76) | 0.0441 |
| Nerve injury | NA | NA |
| Dislocation | 1.56(0.55–4.44) | 0.4074 |
| Prosthesis loosening | 1.14(0.57–2.28) | 0.7147 |
NA, not applicable
PJIs were diagnosed on the basis of the 2018 Musculoskeletal Infection Society criteria. In the control cohort, the most common pathogens were Staphylococcus sp. and Bacillus sp. However, surgical samples collected from patients in the COVID-19 cohort were 25% culture-negative; the pathogens (Fig. 2, 3) were Citrobacter sp. (12.5%), Peptostreptococcus (12.5%), and Staphylococcus sp.(50%). No patient died from any complication within 90 days after surgery.
Fig. 2.
a. Bacterial diversity in the samples intraoperatively collected from the control cohort after PSM. We demonstrated the final culture result in the control cohort with PJI
Fig. 3.
b. Bacterial diversity in the samples intraoperatively collected from the COVID-19 cohort after PSM. We demonstrated the final culture result in the COVID-19 cohort with PJI
Discussion
We demonstrated that a history of COVID-19 is associated with significant increases in the risks of postoperative pneumonia and UTI but not that of 90-day mortality [3, 6, 13–15]. Our finding regarding mortality risk differs significantly from that of Clement et al. but is similar to that of Lim et al. [6, 11] The observed nonsignificant between-cohort difference in mortality rate may be explained by the low rate of emergency surgery (1.96%), higher percentage of patients received surgery before COVID-19 infection (75.2%), and the relatively well-managed health status of patients undergoing elective surgery.
Although studies have reported an association between the history of COVID-19 and the risk of postoperative pneumonia [10–12], an appropriate explanation is still lacking. Considering the systemic effects of COVID-19, we subjected our cohorts to PSM by CCI score. The prevalence of chronic obstructive pulmonary disease was significantly higher in the COVID-19 cohort than in the matched control cohort; this finding explains the higher risk of postoperative pneumonia in the COVID-19 cohort than in the control cohort.
With regard to deep vein thrombosis and pulmonary embolism, multiple studies unrelated to orthopedic surgery have reported an increased risk of VTE in patients with a history of COVID-19 [7–9]. However, inconsistent results have been reported by studies related to orthopedic surgery. Some studies have demonstrated no effects of COVID-19 on the incidence of VTE after total joint arthroplasty and attributed this finding to an optimal postoperative recovery protocol [12–16]. By contrast, other studies have reported an elevated risk of VTE in patients with a history of COVID-19 and attributed this finding to the hypercoagulable state secondary to an imbalance between coagulation and inflammation. Forlenza et al. concluded that the interval between COVID-19 diagnosis and total joint arthroplasty indicates a temporal relationship between this disease and VTE risk [10, 17]. Before PSM in our study, the risk of pulmonary embolism was significantly higher in the COVID-19 cohort than in the control cohort. However, after PSM, this difference became nonsignificant. Thus, the risk of pulmonary embolism may be strongly associated with the general condition of patients and not the history of COVID-19. We did not account for the effects of the interval between COVID-19 diagnosis and total hip arthroplasty; this might have masked the effects of COVID-19 on the risk of pulmonary embolism. Nonetheless, the OR for pulmonary embolism was 4.04 after PSM, implying that pulmonary embolism remains a concern after total hip arthroplasty in patients with a history of COVID-19. Further studies are required to estimate the risks of VTE and pulmonary embolism and assess the need for prophylaxis treatment in this patient population.
Regarding orthopedic complications, PJI differed significantly between the COVID-19 and control cohorts (p = 0.042). However, after PSM by CCI scores, the difference became nonsignificant (OR: 1.62) in multivariate logistic regression. These findings corroborate those of other studies [10, 12] and indicate that the risk of PJI is associated with patients’ general conditions and comorbidities. Before PSM, the level of albumin was relatively low in the COVID-19 cohort that exhibited a high prevalence of diabetes mellitus and hepatitis C—comorbidities that may increase the risk of infection [18–20]. Although this finding may be attributable to selection bias resulting from the fact that only patients with severe COVID-19 tend to visit hospitals, attention should still be paid to the risk of PJI because 25% of patients in our COVID-19 cohort postoperatively developed culture-negative PJI. These infections were diagnosed on the basis of the Musculoskeletal Infection Society minor criteria; thus, confirming the infections was difficult. The prevalence of culture-negative PJI ranges from 0 to 42% [21–23]. In our study, this prevalence was higher in the COVID-19 cohort compared to the control cohort. After PSM, the likelihood of the Girdlestone procedure was found to be significantly higher in the COVID-19 cohort than in the control cohort (p = 0.027). The rate of treatment (irrigation and debridement) failure is approximately 41.67% in patients with culture-negative PJI. However, in a study conducted by Li et al., the overall rate of treatment failure in patients with culture-negative PJI was approximately 19%, which was similar to the rate in patients with culture-positive PJI [24, 25]. Long-term follow-up is essential for accurately evaluating the outcomes of culture-negative PJI in patients with a history of COVID-19 who undergo the Girdlestone procedure.
Another concern in hip arthroplasty is the rate of hip dislocation, which necessitates early revision surgery [26, 27]. In our study, this rate did not differ significantly between the two cohorts, although multivariate logistic regression revealed that this rate was slightly higher in the COVID-19 cohort (OR: 1.56) than in the control cohort. The observed rate is consistent with those reported in studies on primary total hip arthroplasty [28, 29]. The risk of hip dislocation after this primary surgery is attributed to age, surgical approach, major spine disease, and neurologic disease, which were not explored in our study. The observed slight increase in the rate of hip dislocation in the COVID-19 cohort might have resulted from any of the aforementioned reasons. Thus, clinicians must carefully examine their patients’ conditions before surgery.
Limitations
This study has some limitations. First, although this was a multicenter retrospective study, the possibility of selection bias in the COVID-19 cohort cannot be ignored because only patients with severe infection tend to visit hospitals. Second, despite being sufficient for statistical power, the sample size was relatively small. Thus we included patient with recent COVID-19 infection history before or after surgery. Third, we focused on only the short-term outcomes of hip arthroplasty. Finally, to maximize the number of patients in the COVID-19 cohort, we did not differentiate between elective and emergency arthroplasty procedures.
Conclusion
Our study suggests that patients with a history of COVID-19 are at significantly elevated risks of postoperative pneumonia and UTI but not of 90-day mortality or any perioperative complication. Perioperative complications, such as pulmonary embolism, PJI, and hip dislocation, appear to be associated with comorbidity burden rather than COVID-19. In patients with a history of COVID-19, PJIs are difficult to treat because of their culture-negativity; this necessitates the Girdlestone procedure and additional mid-term follow-up is imperative.
Acknowledgements
We thank Ms. Rong Chang for statistical assistance. In addition, we thank the staff at the Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital, for statistical and analytical support.
Author contributions
All authors had access to the data and participated in preparation of the manuscript. Yuhan Chang was responsible for the study design. Shih-Hui Peng was primarily responsible for interpretation of data and drafting the manuscript. Yu-Chin Lin, Chih-Hsiang Chang, Chin-Chien Hu, Lan-Yan Yang were responsible for collecting and analyzing data.
Funding
This study was supported by Chang Gung Memorial Hospital (grant number: CGRPG3N0011).
Data availability
All data generated during this study are included within the manuscript. This study was conducted using data from the Chang Gung Research Database of Chang Gung Memorial Hospital. The findings and conclusions of this study do not represent the opinion of Chang Gung Memorial Hospital.
Declarations
Ethics approval and consent to participate
All procedures involving human participants were performed in accordance with the ethical standards of the institutional research committee, the ethical principles of the 1964 Helsinki Declaration and its later amendments, or comparable ethical standards. Owing to the retrospective nature of this study, formal consent was not required. All experimental protocols were approved by the Biomedical Institutional Review Board of Chang Gung Memorial Hospital (reference: 202201419B0C501). The collected data were anonymized; thus, the requirement for informed consent was waived by the Biomedical Institutional Review Board of Chang Gung Memorial Hospital (reference: 202201419B0C501).
Consent for publication
Not Applicable.
Competing interests
The authors declare no competing interests.
Conflict of interest
The authors declare no conflicts of interest.
Clinical trial number
Not applicable.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
All data generated during this study are included within the manuscript. This study was conducted using data from the Chang Gung Research Database of Chang Gung Memorial Hospital. The findings and conclusions of this study do not represent the opinion of Chang Gung Memorial Hospital.