Dose-response relationship between symptom duration and postoperative patient-reported outcomes in patients with adult spinal deformity

Abstract

Objective

To ascertain whether preoperative symptom duration elevated the risk of adverse patient-reported outcomes (PROs) and to further delve into whether the existence of a dose-response relationship in patients with adult spinal deformity (ASD).

Methods

The retrospective cohort comprised consecutive patients who underwent spinal corrective surgery from January 2018 to May 2022. Demographic, radiological and surgical factors were included from the electronic medical records. To identify the impact of mismatched variables, we performed conditional logistic regression after adjusting for potential confounding factors. Further, nonlinear relationship between symptom duration and postoperative unfavorable PROs at 24-month follow-up was conducted based on restricted cubic splines (RCS) analysis, with the adjustments for possible confounders. If a nonlinear relationship was identified, a two-piecewise regression model would be employed to ascertain the threshold effect. Finally, the result of receiver operating characteristic (ROC) curve was employed to further corroborated the rationality of RCS results.

Results

We matched 122 controls to 61 unfavorable PROs patients. In the fully adjusted linear model, for every additional month of symptom duration, the risk of unfavorable patient-reported outcomes (u-PROs) increased by 79%, with an odds ratio of 1.79 (95% CI: 1.25–2.04, p < 0.001). Patients with 6–18 months of symptom duration had comparable risk of u-PRO, whereas patients with more than 24 months had an increasingly higher risk of u-PRO (OR = 4.74, 95% CI 3.11 − 7.93, p < 0.001). Based on the results of the restricted cubic spline (RCS) analysis with three knots, a significant nonlinear relationship was observed. Notably, we found a substantial increase in the risk of u-PROs when the duration of symptoms exceeded 18.4 months. Additionally, ROC curve with an optimal cut-off of 18.5 months was identified, which verified the reliability of RCS analysis.

Conclusions

We determine that 18.4 months was a threshold of preoperative symptom duration that shifted the risk of unfavorable PROs after spinal corrective surgery, and there was a dose-response relationship.

Introduction

Adult Spinal Deformity (ASD), a complex structural abnormality of the spine, exhibits a diverse array of clinical presentations and is characterized by intricate prognostic factors [1,2,3]. In recent years, significant advancements in biomechanics, spinal anatomy, and imaging technologies have deepened our understanding of spinal deformities. It has become increasingly evident that these deformities not only affect the coronal, sagittal, and axial planes of the spine but also significantly impact long-term patient-reported outcomes (PROs) [4,5,6]. Among the myriad of factors influencing prognosis, the symptom duration has emerged as a pivotal consideration, garnering considerable attention from clinicians [7, 8].

The symptom duration, defined as the period between the onset of spinal deformity-related symptoms and the patient’s initial consultation or treatment, exerts a profound impact on the prognosis of ASD patients. Studies focusing on degenerative lumbar and cervical conditions have demonstrated that early recognition and intervention can significantly slow disease progression, reduce the occurrence of complications, and enhance PROs [9,10,11,12,13]. Accordingly, a prolonged symptom duration, coupled with a lack of timely and effective treatment, may lead to the gradual exacerbation of spinal deformities, culminating in severe structural damage, respiratory dysfunction, cardiac compression, weakened lower extremity strength or paralysis, and even life-threatening conditions in ASD patients [1, 6]. In addition, a prolonged symptom duration is often accompanied by further degeneration of spinal structures and functional decline in ASD patients. For instance, chronic low back and leg pain not only impede daily activities but also predispose patients to secondary conditions in the hip and knee joints, such as flexion contractures, further exacerbating functional impairments [14,15,16,17,18]. Additionally, as spinal deformities progress, alterations in spinal physiology, including the loss of lumbar lordosis and vertebral rotation malalignment, complicate surgical interventions and hinder postoperative recovery [19].

Hence, a thorough exploration of the impact of symptom duration on the prognosis of ASD patients is imperative for guiding clinical decision-making, optimizing treatment strategies, and improving patient outcomes. The study aims to explore the relationship between symptom duration and PROs through propensity score matching (PSM) cohorts. Our findings aim to provide clinicians with more scientific evidence to inform their practice.

Methods

Study design

The study was initiated following approval from the institutional review board (IRB#2024-010-002). Informed consent was waived due to the nature of retrospective study design. Patients undergoing primary thoracolumbar fusion surgery ≥ 5 spinal levels from January 2018 to May 2022 were included. The study included 61 patients with unfavorable PROs (u-PROs) at 24-month follow-up and 122 matched “control” patients [1:2 PSM for age, gender and body mass index (BMI)]. We asked whether there was a correlation between the symptom duration and PROs as well as how symptom duration affected postoperative PROs in these patients. All eligible patients with a confirmed diagnosis of ASD who had failed conservative treatment for at least six months and required surgical intervention met at least one of the following preoperative radiographic inclusion criteria: (1) a pelvic incidence-lumbar lordosis (PI-LL) mismatch of ≥ 10°, (2) a pelvic tilt of ≥ 25°, (3) a sagittal vertical axis of ≥ 5 cm, (4) a thoracic kyphosis of ≥ 60°, or (5) a coronal Cobb angle of ≥ 20°. The exclusion criteria encompassed individuals who were: (1) aged 18 years or younger, (2) had a history of spine surgery, or (3) had spinal deformities caused by tumors, infections, trauma, or neuromuscular conditions.

Surgical procedure

All corrective procedures were meticulously conducted by two experienced spine surgeons through an open approach. The corrective approaches utilized included: (1) A posterior approach that incorporates the Smith-Peterson osteotomy, optionally with a three-column osteotomy, and (2) a combined anterior-posterior approach that includes oblique lumbar interbody fusion and Smith-Peterson osteotomy, with the option to add a three-column osteotomy. The three-column osteotomy is a technically demanding procedure that involves resection of bone and soft tissue across all three columns of the spine (anterior, middle, and posterior). This technique is reserved for patients with severe spinal deformities who require extensive correction in both the sagittal and coronal planes. The anterior column is addressed through discectomy or corpectomy, the middle column through vertebral body resection, and the posterior column through facetectomy and laminectomy. The primary objective of the three-column osteotomy is to achieve a reduction in pelvic incidence-lumbar lordosis (PI-LL) mismatch to below 10°, thereby restoring optimal spinal alignment and function. In terms of instrumentation, the lowest vertebra involved was either the sacrum or the pelvis, whereas the uppermost vertebrae ranged from T9 to L2. Routine practice involved the use of interbody cages for fusion procedures in the lower lumbar region. For the purpose of achieving the necessary correction, bilateral 5.5-mm dual titanium rods were employed.

Data collection

Demographic, radiological, and surgical data were extracted from the electronic medical records. Demographic variables encompassed age, gender, BMI, smoking status, alcohol consumption, Charlson Comorbidity Index (CCI), American Society of Anesthesiologists (ASA) classification, duration of symptoms and frailty (assessed based on mFI-5, a score of ≥ 2 was considered frail). Preoperative radiological parameters such as thoracic kyphosis (TK), lumbar lordosis (LL), pelvic tilt (PT), pelvic incidence (PI), sagittal vertical axis (SVA), and T1 pelvic angle (TPA) were assessed using standard standing lateral whole-spine radiographs from all eligible patients. Surgical factors included the number of fused levels, surgical approach, fusion extending to the sacrum/pelvis, interbody fusion, Schwab grade ≥ 3 osteotomy, operative duration, estimated blood loss (EBL), intraoperative blood transfusion, and reoperation within 24 months postoperatively. Additionally, perioperative complications were documented, with the comprehensive complication index utilized to encapsulate all complications and their severity. Major complications were classified as those with a CCI score exceeding 20 [20].

Outcome measurements

The primary outcome measure was the patient-reported outcomes (PROs), evaluated through the global rating of change (GRC) questionnaire, which employs a 5-point Likert scale ranging from “much better” to “much worse.” This questionnaire assesses whether a patient’s condition has improved, worsened, or remained unchanged following surgical intervention [21]. In contrast to other outcome measures that concentrate on specific health domains like disability or quality of life, the “global” perspective of the GRC enables patients to prioritize and focus on what they deem most significant in assessing their own health status. In this study, patients with the option of much better and slightly better at 24-month follow-up were considered to have favorable PROs (f-PROs), while the remaining patients were thought to have u-PROs.

Statistical analysis

To assess the distribution of numerical variables, histograms and the Shapiro-Wilk test were utilized. For continuous variables, the mean and standard deviation (SD) were employed if they followed a normal distribution; otherwise, the median and interquartile range (IQR) were used. For normally distributed continuous variables, a two-sample t-test was conducted for analysis. In cases of non-normal distribution, the Wilcoxon rank-sum test was applied. Categorical variables were reported using frequency and percentage, and differences between them were determined using either the chi-square test or Fisher’s exact test. Adhering to the guidelines set forth in the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement, we presented the outcomes from three models: the crude model, a minimally adjusted model, and a fully adjusted model. To explore the possibility of a nonlinear relationship, we utilized a smooth curve representation. When a nonlinear relationship was detected, we applied a two-piecewise regression model, guided by the smooth curve, to determine the threshold effect. Additionally, we used the receiver operating characteristic (ROC) curve with the optimal cut-off value to further ascertain the suitable symptom duration. All statistical analyses were conducted using R version 4.3.3 for Windows (R Foundation for Statistical Computing, Vienna, Austria), with statistical significance set at a two-tailed p-value of less than 0.05.

Results

As evident from Table 1, the u-PRO group exhibited comparable characteristics in terms of age, sex, and BMI when compared to the f-PRO group. Risk factors for u-PRO included: higher CCI [odds ratio (OR) 2.53, 95% confidence index (95% CI) 1.45–3.01, p < 0.001] and ASA (OR 1.54, 95% CI 1.17–1.87, p < 0.001). Three radiological factors that increased the risk of u-PRO: preoperative lower LL (OR 0.88, 95% CI 0.69–0.91, p < 0.001), preoperative lower PT (OR 0.78, 95% CI 0.48–0.81, p < 0.001) and preoperative higher SVA (OR 3.97, 95% CI 2.86–6.14, p < 0.001). In addition, reoperation (OR 3.24, 95% CI 2.11–3.67, p < 0.001) significantly increased the risk of u-PRO (Table 2). In the fully adjusted model, which incorporated symptom duration as both a continuous and categorical variable in the multivariable analysis, there was a 79% increase in the risk of u-PRO for every additional month of symptom duration (OR = 1.79, 95% CI 1.25 − 2.04, p < 0.001). Patients with 6–18 months of symptom duration had comparable risk of u-PRO, whereas patients with more than 24 months had an increasingly higher risk of u-PRO (OR = 4.74, 95% CI 3.11 − 7.93, p < 0.001) (Table 3). A significant nonlinear relationship was observed based on the results of the restricted cubic spline (RCS) with 3 knots. Notably, there was a substantial elevation in the risk of u-PRO when the symptom duration surpassed 18.4 months (Fig. 1; Table 4). Additionally, ROC curve with a optimal cut-off of 18.5 months was identified, which verified the reliability of RCS analysis (Fig. 2).

Table 1 Subject characteristics for u-PROs and matched f-PROs

Table 2 Univariate conditional logistic regression analysis of variables associated with u-PROs

Table 3 Relationship between preoperative symptom duration and u-PROs

Fig. 1

The result of nonlinear relationship between preoperative symptom duration and unfavorable PROs evaluated with restricted cubic spline curve

Table 4 Two-piecewise regression model

Fig. 2

Receiver operating curves analysis for preoperative symptom duration against unfavorable PROs to determine the optimal cutoff value

Discussion

To our knowledge, this study represents the first exploration of the complex relationship between symptom duration and postoperative PROs in individuals with ASD. In this analysis of 183 patients with ASD, we explored the association between symptom duration and PROs at 2-year follow-up following elective spinal corrective surgery. Overall, we found symptom duration exerts a threshold effect on PROs in patients with ASD based on RCS analysis. Patients with preoperative symptom duration > 18.4 months demonstrated a significant increase risk of unfavorable PRO.

ASD, an intricate and demanding spinal condition, encompasses a diverse array of adult-onset spinal disorders. These include adult scoliosis, degenerative scoliosis, imbalances in both the sagittal and coronal planes, and iatrogenic deformities, with or without spinal stenosis [1, 3]. Approximately 60% of elderly patients are impacted by ASD, which contributes to a decline in their health-related quality of life [22]. ASD typically manifests with symptoms such as low back pain, radiating pain, and intermittent claudication. Prior to spinal corrective surgery, patients are usually treated conservatively. Nevertheless, the precise duration of conservative therapy that yields the best results remains uncertain. A longer duration of symptoms has been well-documented as a risk factor for unfavorable outcomes in orthopedic surgical procedures [7, 10, 13], although there existing conflicting results. In a retrospective analysis of 144 patients who underwent lumbar fusion at 1–3 levels, Johnson et al. found that those with symptoms lasting more than 2 years prior to surgery experienced a smaller improvement in physical function, as measured by the Patient-Reported Outcomes Measurement Information System (PROMIS-PF), and were less likely to achieve the minimal clinically important difference (MCID) in PROMIS-PF scores [10]. However, based on clinical and radiographic assessments, Sayari et al. observed no correlation between symptom duration and outcome, and advocated for maximizing conservative treatment to avoid surgical intervention. Such conflicting results may attribute to the inclusion of heterogeneous pathology or surgical techniques. As ASD involves intricate pathological trajectory unlike degenerative lumbar conditions, a knowledge gap persists in the literature concerning how preoperative symptom duration correlates with PROs following corrective surgical procedures. In addition, the models used in previous literature that explore the correlation between symptom duration and PROs were generalized linear models, and fail to discuss continuous variables and nonlinear relationships. The reliance on generalized linear models constrained the capacity to uncover curvilinear patterns and dose-response effects, which are prevalent in biomedical contexts [23]. Furthermore, the heterogeneous of included patients may introduce the possibility of bias. Therefore, in this study, to reduce bias and maintain comparability of patients’ characteristics, we conducted PSM prior to data analysis. Additionally, we separately performed both generalized linear and non-linear analysis to explore the complicated relationship between symptom duration and PROs in patients with ASD. Consistent with other studies exploring the influence of symptom duration on PROs in patients following lumbar fusion surgery, our study indicated prolonged symptom duration implied unfavorable PROs at 24-month follow-up based on linear model. It is worth noting that there existing threshold effect between symptom duration and PROs with a cutoff of 18.4 months based on RCS analysis. The result of ROC curve further corroborated the rationality of RCS results.

Our results suggest that prompt surgical intervention may prove advantageous for patients in obtaining desirable outcomes. However, our data does not establish a direct causal relationship between the length of symptoms and outcomes, as the influence of prolonged symptoms on postoperative results is likely influenced by multiple factors. Patients with prolonged symptom duration may experience a greater degree of deconditioning and decline in physical function. Consequently, restoring optimal spinal function and achieving patient satisfaction may necessitate a longer duration [24]. Furthermore, prolonged nerve root compression necessitates an extended recovery period for the damaged nerve root even after compression is relieved [2, 25]. The research highlights the necessity of immediate and appropriate interventions for patients. One major factor leading to prolonged preoperative symptoms is the excessive duration of attempting conservative management. It is important for patients to receive an appropriate degree of conservative care before considering surgical intervention. However, this study underscores the necessity for surgeons to be aware of the risks of deteriorated outcomes linked to delayed surgical procedures. Therefore, patients ought to undergo regular follow-up and, when indicated, appropriate surgical intervention. In addition, recognizing that longer symptom duration serves as a predictor of worse outcomes in patients undergoing corrective surgery allows clinicians to better advise patients regarding postoperative expectations that could contribute to a delayed surgery, as previous literature implied higher preoperative expectation indicates worse patient satisfaction [26, 27].

Several considerations should be taken into account when interpreting the results of this study. Firstly, one of the limitations of this study is its relatively small sample size and single-center design, which may restrict the generalizability of the findings. While our results provide valuable insights into the dose-response relationship between preoperative symptom duration and postoperative patient-reported outcomes (PROs), multi-center studies with larger and more diverse populations are warranted to validate these findings and explore potential variations in delayed complications across different healthcare settings. Secondly, the retrospective design of this study introduces potential biases, such as delays in diagnosis, excessive use of conservative treatment, or patients’ own decisions to postpone surgery, all of which could impact outcomes in various ways. Furthermore, preoperative symptom duration data, derived from patient reports in electronic medical records, are subjective and may lack precision. Finally, this study did not distinguish the symptom characteristics (i.e. neurogenic claudication or radicular symptom), location and severity of symptoms in detail, which may have potential impact on the generalization of the present findings, as previous study have indicated that the severity and duration have higher predictive importance in obtaining patient satisfaction and achieving MCID in Oswestry Disability Index [9]. Therefore, given the potential diversity within the cohorts based on symptom duration, our results should be interpreted with this factor in mind.

Conclusion

In the present study, we found that a preoperative symptom duration > 18.4 months significantly increases the risk of unfavorable PROs based on RCS analysis in patients undergoing spinal corrective surgery. It is crucial to prioritize prompt referrals following the inadequacy of conservative measures to ensure that patients receive the surgical care they may require.