Abstract
Background
Posterior lumbar fusion (PLF) is a common spine surgery that may be considered in patients with underlying comorbidities, such as inflammatory bowel disease (IBD). Prior literature examining the association of this disease and PLF outcomes was done in the National Inpatient Sample (NIS), which only assessed in-hospital data and did not reveal an elevated risk of medical or surgical complications. However, characterization of PLF outcomes beyond hospital discharge is important and remains unknown for patients with IBD.
Methods
Patients with IBD who underwent single-level PLF ± interbody fusion were identified from the M165Ortho PearlDiver database. Exclusion criteria included: patients <18 years old, those undergoing concurrent cervical, thoracic, anterior, or multi-level fusion, those with prior trauma, neoplasm, or infection diagnosed within 90-days, and <90-days of follow-up. Adult patients with IBD were matched 1:4 with non-IBD patients based on age, sex, and Elixhauser Comorbidity Index (ECI). The odds of 90-day individual and aggregated any, severe, and minor adverse events (AAE, SAE, and MAE, respectively), emergency department (ED) visits, and hospital readmission were compared by multivariable logistic regression. Five-year reoperation was assessed by Kaplan-Meier survival analysis and compared by log-rank test.
Results
Overall, 4,392 (1.4%) of patients undergoing PLF were identified with IBD. These patients demonstrated elevated odds ratios (ORs) of aggregated MAE (OR 2.29), AAE (OR 2.27), and SAE (OR 1.84), as well as ED visits (OR 2.69) (p<.001 for all). Conversely, 5-year reoperation rates were not different for those with vs without IBD (p=.70).
Conclusions
The current study highlights the importance of investigating post-discharge outcomes, as these findings were not detected by prior inpatient literature. Our findings reveal the odds of various complications may be significantly elevated for IBD patients within 90-days postoperatively, however, these inferior outcomes encouragingly did not translate to an elevated rate of 5-year reoperation.
Keywords: Inflammatory bowel disease; Ibd; Ulcerative colitis; Crohn's disease; Posterior lumbar fusion, Outcomes; Complications
Introduction
There is a growing emphasis on optimizing postoperative outcomes following posterior lumbar fusion (PLF) in patients with various underlying comorbidities [[1], [2], [3], [4], [5]]. One such comorbidity, which affects over 3.1 million people in the United States [6], is inflammatory bowel disease (IBD). This prevalence in the is among the highest in the world [7,8], suggesting this disease may be present in a significant percentage of patients in the United States considered for PLF.
This disease is comprised of ulcerative colitis and Crohn's disease, which both affect the gastrointestinal (GI) system through aberrant immunologic activation of the inflammatory cascade [9,10]. IBD arises from cytokine driven inflammation, manifesting as both constitutional and GI symptoms in a chronic relapsing-remitting pattern that persists throughout life, and often associated with a myriad of extraintestinal manifestations.
The most common orthopaedic manifestation of IBD is low bone mineral density [11]. This manifestation is due to altered bone metabolism [12], and frequent poor nutritional status in these patients [13], which has been associated with higher rates early onset osteoporosis [14,15], and vertebral fracture [16]. Additionally, IBD patients undergoing total joint arthroplasty have demonstrated higher risk of inferior postoperative outcomes such as nosocomial infection [17], prosthetic joint infection [[17], [18], [19]], periprosthetic fracture [18], venous thromboembolism [20], and revision surgery [[21], [22], [23]].
Tanenbaum et al. [24] used the National Inpatient Sample (NIS) to assess patients with IBD undergoing PLF, reporting longer length of stay (LOS), greater hospital cost, but no difference in medical or surgical in-hospital complications. However, these outcomes were exclusively studied during the index hospital admission with a median LOS of 4 days, thereby limiting our understanding of the implications of IBD on post-discharge outcomes.
Furthermore, the utilization of corticosteroids, 5-aminosalicylic acid (5-ASA) agents, immunosuppressants, and biologics are common therapeutic strategies to induce remission and manage chronic IBD symptoms [25]. Despite their profound efficacy in symptom management, an independent association with medication induced fracture [26], osteoporosis [27,28], and postoperative complications, such as infection, sepsis, and poor wound healing have been reported [[29], [30], [31], [32]].
The paucity of literature investigating the association of IBD on PLF outcomes extending past hospital discharge prompted the current study, which leveraged a large, national, multi-insurance administrative dataset to investigate 90-day complications, 5-year reoperation, and the association of exposure to various therapeutic agents among patients with IBD undergoing PLF.
Methods
Data source and inflammatory bowel disease study population
Data was abstracted from the 2010 – Q3 2022 PearlDiver Mariner 165 database (PearlDiver Technologies, Colorado Springs, CO, USA). This is a large, national, multi-insurance administrative claims database which contains over 165 million patient records. The use of this database has been well established in the orthopaedics/spine literature [[33], [34], [35], [36], [37]]. As data from this database are de-identified, our institutional review board found studies using these data exempt from review.
Adult patients with IBD who underwent single-level PLF ± interbody fusion was identified by International Classification of Disease (ICD) and Current Procedural Terminology (CPT) coding, respectively. Exclusion criteria included: patients < 18 years of age, those undergoing concurrent cervical, thoracic, anterior, or multi-level fusion, those with prior trauma, neoplasm, or infection diagnosed within 90-days, and those with <90-days of follow-up.
Demographic data abstracted included age, sex, and Elixhauser Comorbidity Index (ECI, a measure of overall comorbidity burden) [38]. Patients with and without IBD who underwent PLF were matched 1:4 using an exact match methodology [39] within the PearlDiver Bellwether software by age, sex, and ECI to account for potential differences in underlying patient demographics and comorbidity burden. A successful match resulted in populations with the same proportional patient demographic characteristics.
IBD study population stratified by therapeutic exposure
Patients with IBD who underwent PLF were then stratified by exposure to therapeutic agents within 12-months preoperatively. Since corticosteroids are often used to induce remission during an IBD flare-up, but not recommended as long-term therapy, patients exposed to these agents were studied on their own (corticosteroid only group) and included among the other therapeutic agent groups (± steroids).
These therapeutic agent groups were exclusively stratified: corticosteroids only (including budesonide, prednisone, hydrocortisone, prednisolone, or methylprednisolone), 5-ASA agents (including mesalazine, sulfasalazine, balsalazide, or olsalazine) ± steroids, immunosuppressants (including mercaptopurine, cyclosporine, tacrolimus, azathioprine, methotrexate, or tofacitinib) ± steroids, and biologics (including vedolizumab, infliximab, adalimumab, golimumab, natalizumab, or ustekinumab) ± steroids.
Among these therapeutic exposure cohorts, demographic data including age, sex, and ECI were abstracted. Patients with IBD undergoing PLF within each therapeutic exposure group were then matched 1:1 with IBD patients without any medication exposure using an exact match methodology [39] within the PearlDiver Bellwether software by age, sex, and ECI. A successful match resulted in populations with the same proportional patient demographic characteristics.
Postoperative adverse events
The occurrence of 90-day individual and aggregated any, severe, and minor adverse events (AAE, SAE, MAE, respectively) were first determined for the matched populations with and without IBD and compared by univariable and multivariable analysis. The identified SAEs included sepsis, surgical site infection, cardiac events (including myocardial infarction or cardiac arrest), and venous thromboembolism (including deep vein thrombosis or pulmonary embolism).
The identified minor adverse events included pneumonia, urinary tract infection, acute kidney injury, wound complication (including wound dehiscence and hematoma), and transfusion. Occurrences of 90-day postoperative emergency department (ED) visit were determined. Hospital readmission within the 90-day postoperative period were identified using the PearlDiver “admission” function that identifies relevant inpatient ICD codes.
To determine 5-year reoperation free survival of patients with IBD vs non-IBD controls, the occurrence of any subsequent lumbar surgery was determined within 5-years of the index procedure by tracking all lumbar spine surgery CPT codes within that timeframe.
Subsequent analyses among patients with IBD stratified by preoperative medication exposure were then performed. The odds of aggregated 90-day AAE were determined relative to matched IBD patients without any medication exposure by multivariable analysis.
Statistical analysis
Characteristics including mean age, sex, and ECI were tabulated for each patient with and without IBD and compared using an independent 2-tailed student t-test or Pearson χ²-test where appropriate. These comparisons were repeated after matching, p<.05 was considered significant.
Univariable comparison of the 90-day occurrence of adverse events were determined by Pearson χ²-test. Multivariable logistic regression controlling for age, sex, and ECI of all individual and aggregated adverse events was performed for patients with relative to without IBD to determine the odds ratio (OR) and 95% confidence interval (CI) of postoperative complications.
The 5-year reoperation free survival was determined by Kaplan-Meier survival analysis with log-rank (Mantel-Cox) test utilized to statistically analyze the rates of reoperation between (+)IBD patients relative to (-)IBD controls.
For the subsequent stratified analyses based on exposure to therapeutic agents, characteristics including mean age, sex, and ECI were tabulated for each group and compared with IBD patients in the no medication exposure cohort by univariable analysis using an independent 2-tailed student t-test or Pearson χ²-test where appropriate. These comparisons were repeated after matching, p<.05 was considered significant.
A separate multivariable logistic regression was performed controlling for age, sex, and ECI to determine the OR and 95% CI of aggregated 90-day AAE for IBD patients within each therapeutic cohort, relative to matched IBD patients without any medication exposure.
All statistical tests were performed using R version 4.2.1 (R Foundation for Statistical Computing, Vienna, Austria) embedded within the R statistical package of the PearlDiver Bellwether software, with a p-value of <.05 considered significant. Tables were constructed using Microsoft Excel (Microsoft Corporation, Redmond, WA) and figures were created with Prism 10 (GraphPad Software, San Diego, CA).
Results
IBD study population
In total, 302,012 (98.6%) (-)IBD and 4392 (1.4%) (+)IBD patients undergoing PLF were identified (Table 1). In the unmatched groups, those with IBD were younger, more frequently female, and higher ECI (p<.001 for all).
Table 1.
Patient Demographics of unmatched and matched patients undergoing single-level PLF with and without IBD.
| Unmatched Population |
4:1 Matched Population |
|||||
|---|---|---|---|---|---|---|
| PLF (-)IBD | PLF (+)IBD | p-value | PLF (-)IBD | PLF (+)IBD | p-value | |
| n=302,012 | n=4392 | n=17,237 | n=4321 | |||
| Age ± SD | 61.3±12.2 | 57.8±11.6 | <.001 | 58.2±11.3 | 58.1±11.3 | .858 |
| Sex | <.001 | .958 | ||||
| Female | 174,466 (57.8%) | 2705 (61.6%) | 10,633 (62.7%) | 2663 (61.6%) | ||
| Male | 127,546 (42.2%) | 1687 (38.4%) | 6604 (38.3% | 1658 (38.4%) | ||
| ECI ± SD | 4.1±3.4 | 6.3±4.0 | <.001 | 6.2±3.8 | 6.2±3.9 | .751 |
After matching, there were 17,237 (-)IBD and 4321 (+)IBD patients. In these matched cohorts, there were no longer differences in age, sex, or ECI (p>.05 for all).
IBD study population stratified by therapeutic exposure
Among patients with IBD who underwent PLF based on preoperative medication exposure (Fig. 1, Table 2), a total of 1329 (33.5%) were identified without medication exposure, 1164 (29.3%) exposed to corticosteroids only, 676 (17.0%) exposed to 5-ASA agents ± steroids, 607 (15.3%) exposed to immunosuppressant agents ± steroids, and 191 (4.8%) exposed to biologic agents ± steroids. In these unmatched groups various demographic factors were statistically different relative to IBD patients without medication exposure.
Fig. 1.
Pie chart demonstrating the distribution of preoperative exposure to therapeutic agents for patients with inflammatory bowel disease (IBD) undergoing posterior lumbar fusion (PLF).
Table 2.
Unmatched patient demographics of those with IBD undergoing single-level PLF stratified by preoperative therapeutic exposure to medications.
| n (%) | No Meds (Reference) |
Corticosteroid Only |
5-ASA ± Steroid |
Immunosuppressant ± Steroid |
Biologic ± Steroid |
||||
|---|---|---|---|---|---|---|---|---|---|
| 1329 (33.5%) | 1164 (29.3%) | p-value | 676 (17.0%) | p-value | 607 (15.3%) | p-value | 191 (4.8%) | p-value | |
| Age ± SD | 58.7±11.4 | 58.2±12.6 | .349 | 59.1±11.5 | .487 | 59.1±10.5 | 0.382 | 56.6±11.1 | .015 |
| Sex (%) | .424 | 1.000 | .005 | .227 | |||||
| Female | 791 (59.5) | 712 (61.2) | 403 (59.6) | 403 (66.4) | 123 (64.4) | ||||
| Male | 538 (40.5) | 452 (38.8) | 273 (40.4) | 204 (33.6) | 68 (35.6) | ||||
| ECI ± SD | 5.7±3.8 | 6.5±4.1 | <.001 | 4.6±3.3 | <.001 | 5.5±3.7 | .244 | 5.6±4.0 | .620 |
After independent matching of each therapeutic exposure cohort with IBD patients not exposed to medications (Table 3), equal cohort populations resulted, which no longer differed in age, sex, or ECI (p>.05 for all).
Table 3.
Individually matched patient demographics of those with IBD undergoing single-level PLF based on therapeutic medication exposure.
| Matched No Meds | Matched Corticosteroid Only |
Matched No Meds | Matched 5-ASA ± Steroids |
Matched No Meds | Matched Immunosuppressant ± Steroids |
Matched No Meds | Matched Biologic ± Steroids |
|||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| n=546 | n=546 | p-value | n=416 | n=416 | p-value | n=366 | n=366 | p-value | n=111 | n=111 | p-value | |
| Age ± SD | 59.5±10.3 | 59.5±10.3 | 1.00 | 60.8±9.6 | 60.8±9.6 | 1.00 | 60.6±8.6 | 60.6±8.6 | 1.00 | 57.9±8.9 | 57.9±8.9 | 1.00 |
| Sex (%) | 1.00 | 1.00 | 1.00 | 1.00 | ||||||||
| Female | 339 (62.1) | 339 (62.1) | 274 (65.9) | 274 (65.9) | 262 (71.6) | 262 (71.6) | 76 (68.5) | 35 (31.5) | ||||
| Male | 207 (37.9) | 207 (37.9) | 142 (34.1) | 142 (34.1) | 104 (28.4) | 104 (28.4) | 76 (68.5) | 35 (31.5) | ||||
| ECI ± SD | 5.4±3.2 | 5.4±3.2 | 1.00 | 4.5±2.8 | 4.5±2.8 | 1.00 | 5.2±3.0 | 5.2±3.0 | 1.00 | 5.0±3.2 | 5.0±3.2 | 1.00 |
Postoperative adverse events
The results of a univariable and multivariable analysis of 90-day outcomes following single-level PLF in matched patients with and without IBD are shown (Table 4). By univariable analysis of patients with compared to without IBD, those with IBD exhibited higher incidence of various postoperative complications.
Table 4.
Univariable and multivariable analysis of 90-day postoperative adverse events following single-level PLF in patients with relative to without IBD.
| Univariable Analysis |
Multivariable Analysis |
||||
|---|---|---|---|---|---|
| Matched PLF (-)IBD | Matched PLF (+)IBD | Matched PLF (+)IBD | |||
| n=17,237 | n=4321 | ||||
| n (%) | n (%) | p-value | OR (95% CI) | p-value | |
| Any Adverse Event | 3215 (18.7) | 1435 (33.2) | <.001 | 2.27 (2.10–2.45) | <.001 |
| Severe Adverse Event | 1569 (9.1) | 663 (15.3) | <.001 | 1.84 (1.66–2.03) | <.001 |
| Sepsis | 419 (2.4) | 203 (4.7) | <.001 | 1.99 (1.68–2.03) | <.001 |
| Surgical Site Infection | 804 (4.7) | 237 (5.5) | .027 | 1.18 (1.02–1.37) | .027 |
| Cardiac Event | 153 (0.9) | 67 (1.6) | <.001 | 1.76 (1.31–2.34) | <.001 |
| Venous Thromboembolism | 501 (2.9) | 251 (5.8) | <.001 | 2.07 (1.77–2.42) | <.001 |
| Minor Adverse Event | 2378 (13.8) | 1121 (25.9) | <.001 | 2.29 (2.11–2.49) | <.001 |
| Pneumonia | 428 (2.5) | 259 (6.0) | <.001 | 2.53 (2.16–2.97) | <.001 |
| Urinary Tract Infection | 982 (5.7) | 635 (14.7) | <.001 | 2.99 (2.68–3.33) | <.001 |
| Acute Kidney Injury | 604 (3.5) | 258 (6.0) | <.001 | 1.79 (1.53–2.09) | <.001 |
| Wound Complication | 189 (1.1) | 56 (1.3) | .305 | 1.18 (0.87–1.58) | .276 |
| Transfusion | 310 (1.8) | 141 (3.3) | <.001 | 1.85 (1.51–2.26) | <.001 |
| Healthcare Utilization | – | – | – | – | – |
| Emergency Department Visit | 2786 (16.2) | 1417 (32.8) | <.001 | 2.69 (2.49–2.91) | <.001 |
| Hospital Readmission | 1742 (10.1) | 421 (9.7) | .495 | 0.96 (0.85–1.07) | .434 |
Patients with IBD demonstrated elevated odds of the majority of individually assessed 90-day complications (Table 4, Fig. 2), as well as all aggregated adverse events: MAE (OR 2.29), AAE (OR 2.27), SAE (OR 1.84), and ED visits (OR 2.69) (p<.001 for all).
Fig. 2.
Forest plot of odds ratios (ORs) with 95% confidence intervals of the multivariable analysis of 90-day adverse events following posterior lumbar fusion (PLF) in patients with versus without inflammatory bowel disease (IBD). Filled black circles denote significant ORs. Unfilled circles denote nonsignificant ORs.
Kaplan-Meier analysis for the 5-year reoperation free survival for IBD patients compared with non-IBD controls is shown (Fig. 3). The rates of reoperation free survival were not statistically different between patients with vs without IBD by log rank test (88.0% vs 87.9%, respectively) (p=.70).
Fig. 3.
Kaplan-Meier curve of 5-year reoperation free survival following posterior lumbar fusion (PLF) in patients with inflammatory bowel disease (IBD) versus non-IBD controls.
Odds of AAE for patients with IBD stratified by preoperative therapeutic exposure to medication is shown (Table 5, Fig. 4). Relative to patients with IBD not preoperatively exposed to medications, patients exposed to biologic agents ± steroids were associated with greater odds of AAE (OR 2.28, p=.008). Conversely, patients exposed to corticosteroids, 5-ASA agents, or immunosuppressants were not independently associated with greater odds of postoperative complications (p>.05 for all).
Table 5.
Multivariable analysis of any adverse event following PLF in IBD patients with relative to without therapeutic medication exposure within 12-months preoperatively.
| OR (95% CI) | p-value | |
|---|---|---|
| No Therapeutic Exposure | Reference | Reference |
| Corticosteroid Only | 0.85 (0.65–1.10) | 0.219 |
| 5-ASA ± Steroid | 1.11 (0.82–1.52) | 0.695 |
| Immunosuppressant ± Steroid | 1.06 (0.76–1.46) | 0.332 |
| Biologic ± Steroid | 2.28 (1.25–4.26) | 0.008 |
Fig. 4.
Forest plot of odds ratios (ORs) with 95% confidence intervals of the multivariable analysis of any 90-day adverse event following posterior lumbar fusion (PLF) in patients with inflammatory bowel disease (IBD) with relative to without preoperative medication exposure. Filled black circles denote significant ORs. Unfilled circles denote nonsignificant ORs.
Discussion
IBD is an inflammatory disease with systemic effects, often managed by utilization of various therapeutic agents [9,10,25]. The findings of the current study revealed that patients with IBD undergoing PLF are associated with greater odds of various postoperative complications within 90-days following surgery, but did not demonstrate inferior 5-year reoperation free survival. These findings are inconsistent with prior literature of exclusively in-hospital outcomes, which revealed IBD was not associated with postoperative complications [24], highlighting the importance of studying patients throughout their postoperative course.
The current study found that patients with IBD who underwent PLF were associated with higher odds of postoperative infectious adverse events including sepsis, surgical site infection, urinary tract infection, and pneumonia. This is consistent with prior literature among patients with IBD undergoing total joint arthroplasty, which found these patients were at greater odds of infection, pneumonia, and UTI [20]. These findings may be due to an underlying susceptibility to infection [40,41], which is postulated to be due to the immunologic dysfunction seen in IBD [42].
Our finding that patients with IBD had greater odds of coagulopathy related complications such as VTE, cardiac events, and transfusion may be explained by the induction of a hypercoagulable state by inflammatory cytokines in the pathogenesis of IBD [43,44]. A prior meta-analysis by Xu et al. [20] corroborates this association, which reported that IBD demonstrated an increased risk of coagulopathy related events following total joint arthroplasty.
Additionally, the current study found patients with IBD to have higher odds of ED visit within 90-days, which is likely related to the development of the aforementioned postoperative complications. This finding is consistent with prior literature, which revealed that patients with IBD had higher rates of overall healthcare utilization and ED visits [45]. Despite this, the current study found no association with hospital readmission, suggesting that although patients with IBD may be more prone to emergency healthcare service utilization, the odds of requiring admission for hospital-level care is not elevated following PLF.
Together, the heightened odds of postoperative adverse events occurring within 90-days following PLF identify this as a timeframe deserving particular attention, however, patients with IBD were not found to have elevated rates of reoperation within 5 years. This important finding may inspire confidence for orthopaedic surgeons performing PLF, suggesting that patients who are surgical candidates for PLF should not be limited by their underlying IBD in the lens of long-term outcomes of this treatment strategy.
Patients with IBD are prescribed a variety of therapeutic agents to manage their disease [25]. However, due to the systemic effects of these medications, an independent association with inferior surgical outcomes in patients with IBD has been reported [31,32]. The current study found that relative to IBD patients not exposed to therapeutic agents preoperatively, those exposed to corticosteroids, 5-ASA medications, or immunosuppressive agents within the year prior to PLF were not at elevated risk of adverse events. Conversely, patients exposed to biologic agents demonstrated a significant association with greater odds of postoperative complications.
While this association is likely multifactorial, exposure to biologic agents has shown to independently increase the risk of adverse events, most notably infection [[46], [47], [48]]. However, it should be highlighted that the findings of the current study do not reflect a causal association with inferior surgical outcomes. It is important to consider that patients with IBD who utilize biologic agents may have more severe disease, not adequately controlled by the other therapeutics. These important qualifications suggest that future prospective analysis is warranted to further elucidate this association. Furthermore, the challenge of advising a patient to preoperatively alter their therapeutic regimen must be weighed against a possible symptom flare [49], and a multidisciplinary approach to this clinical decision is likely beneficial.
While this is the first assessment of the association between IBD and PLF outcomes extending to 5-years postoperatively, it is not without limitations. As with any administrative database study, it is limited by the coded data utilized. The importance of patient-level disease manifestations, which are not well-captured by ICD coding, deserve further analysis. Finally, the day-by-day granularity of perioperative therapeutic cessation, which is not well-captured by prescription drug coding, should be considered in future research aimed at optimizing care for the studied patient population.
In summary, the current study highlights the importance of investigating post-discharge outcomes, as these findings were not detected by prior inpatient literature. Our findings reveal the odds of various complications may be significantly elevated for IBD patients within 90-days postoperatively, however, these inferior outcomes encouragingly did not translate to an elevated rate of 5-year reoperation.
Declaration of competing interest
Jonathan N. Grauer. is the North American Spine Society Journal Editor-in-chief and member of the North American Spine Society Board
Acknowledgments
None.
Footnotes
FDA device/drug status: All therapeutic agents included in the current study are FDA approved for the management of inflammatory bowel disease. Those included are 5- aminosalicyclic-acid agents (mesalazine, sulfasalazine, balsalazide, olsalazine), immunosuppressant agents (mercaptopurine, cyclosporine, tacrolimus, azathioprine, methotrexate, tofacitinib), biologic agents (vedolizumab, infliximab, adalimumab, golimumab, natalizumab, ustekinumab), and steroids (budesonide, prednisone, hydrocortisone, prednisolone, methylprednisolone).
Author disclosures: AES: Nothing to disclose. BMK: Nothing to disclose. JS-V: Nothing to disclose. MJG: Nothing to disclose. WD: Nothing to disclose. SSJ: Nothing to disclose. RSV: Nothing to disclose. DRR: Nothing to disclose. JNG: Board of Directors: NASSJ (D).
Given his role as Editor in Chief, Jonathan Grauer, MD had no involvement in the peer-review of this article and has no access to information regarding its peer-review. Full responsibility for the editorial process for this article was delegated to Tobias Mattei, MD.
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