Xiong, Ashley

Abstract Background The Global Bipolar Cohort (GBC) was established to identify existing bipolar disorder (BD) cohorts worldwide and foster collaborations focused on descriptive and analytic outcomes relevant to BD. A distributed analytic framework has been implemented to engage multiple sites without the need for central data pooling. This report describes the GBC endeavor and global functional impairment patterns. Cross-cohort comparisons of functional correlates are limited by heterogeneous measures and data-sharing constraints. Large, culturally diverse comparisons are needed to distinguish broadly reproducible correlates from cohort-specific effects. Participating sites completed a 28-item descriptive survey covering diagnostic methods, cognition, genetics, treatment, functioning, and follow-up strategies. We implemented a harmonized local logistic regression model of dichotomized functional outcome and shared summary statistics only. Results We identified 69 cohorts across five continents. Thirty-seven cohorts contributed functional outcome analyses from 17,130 participants. Outcome measures included clinician-rated disability scales and social indicators such as employment and marital status. The proportion classified with poor functioning ranged from 16% to 77% (mean 50%). In 32 of 37 cohorts, the overall regression model significantly explained variance in functioning. Current depressive symptoms were the most robust and reproducible correlate of poor functional outcome: they were assessed in 29 cohorts, significant in 22 (75.8%), ranked among the top three correlates in 22, and were the top-ranked correlates in 19. Associations between depressive burden and poor functioning were observed across clinician-rated disability scales and work or social indicators, and across geographically diverse cohorts. Comorbid substance use disorder and medication-related variables were associated with poorer functioning in subsets of cohorts, whereas sex, ancestry, bipolar subtype, psychosis history, and premorbid IQ showed weak or inconsistent associations. Cognitive measures, available in a minority of regression models, showed modest and non-uniform effects. Conclusions Across heterogeneous international cohorts, current depressive symptom burden emerged as the most consistent correlate of poor functioning in bipolar disorder. These findings replicate earlier multisite work at a larger scale, show that protocol-based distributed analyses can identify reproducible clinical signals without sharing individual-level data, and support prioritizing detection and treatment of depressive symptoms when aiming to improve real-world functioning. Future work should expand longitudinal harmonization and representation of under-studied populations.

In this case series, we present several examples from participants (2 patients and 1 healthy control) of a 12-week pilot feasibility study to create a digital phenotype of depression (unipolar or bipolar) through active and passive data collection from a smartphone and a wearable device combined with routine clinical care for mood disorders. The selected cases represent real clinical examples that highlight the intrinsic challenges that should be expected when conducting similar studies, including appropriate health data privacy protection, clinical standardization, and interindividual differences in levels of engagement and acceptability of active and passive data collection (ie, self-reported, behavioral, cognitive, and physiological data), particularly with patient-generated data in mobile apps, digital proficiency habituation, and consistent use of wearable devices. In the context of the rapidly growing use of digital technologies in psychiatry, anticipating challenges for the integration of personal mobile devices and smartphone mental health apps as aides to track specific aspects of depressive disorders is critical for a clinically meaningful digital transformation of mood disorders care.

Study Design: This was a multicenter retrospective cohort study. Objective: The purpose of this study was to compare the surgical and radiographic outcomes of patients undergoing posterior cervical fusion (PCF) with constructs extending from C2 to T2 to patients with constructs extending from C3 to T1. Summary of Background Data: Limited evidence exists regarding the appropriate level of proximal and distal extension of PCF constructs. Methods: A multicenter retrospective cohort study of patients who underwent PCF between 2012 and 2020 was performed. Surgical and radiographic outcomes were compared between those who had C3–T1 or C2–T2 constructs. Results: A total of 155 patients were included in the study (C2–T2: 106 patients, C3–T1: 49 patients). There were no significant differences in demographics or preoperative symptoms between cohorts. Fusion rates were significantly higher in the C2–T2 (93%) than the C3–T1 (80%, P=0.040) cohort. When comparing the C2–T2 to the C3–T1 cohort, the C3–T1 cohort had a significantly greater rate of proximal junctional failure (2% vs. 10%, P=0.006), distal junctional failure (1% vs. 20%, P<0.001) and distal screw loosening (4% vs. 15%, P=0.02). Although ∆C2–C7 sagittal vertical axis increased significantly in both cohorts (C2–T2: 6.2 mm, P=0.04; C3–T1: 8.4 mm, P<0.001), correction did not significantly differ between groups (P=0.32). The C3–T1 cohort had a significantly greater increase in ∆C2 slope (8.0 vs. 3.1 degrees, P=0.03) and ∆C0–C2 Cobb angle (6.4 vs. 1.2 degrees, P=0.04). Conclusion: In patients undergoing PCF, a C2–T2 construct demonstrated lower rates of pseudarthrosis, distal junctional failure, proximal junctional failure, and compensatory upper cervical hyperextension compared with a C3–T1 construct.

Study Design Retrospective cohort study Objective Substantial variability in both the measurement and classification of subsidence limits the strength of conclusions that can be drawn from previous studies. The purpose of this study was to precisely characterize patterns of cervical cage subsidence utilizing computed tomography (CT) scans, determine risk factors for cervical cage subsidence, and investigate the impact of subsidence on pseudarthrosis rates. Methods We performed a retrospective review of patients who underwent one- to three-levels of anterior cervical discectomy and fusion (ACDF) utilizing titanium interbodies with anterior plating between the years 2018 and 2020. Subsidence measurements were performed by two independent reviewers on CT scans obtained 6 months postoperatively. Subsidence was then classified as mild if subsidence into the inferior and superior endplate were both ≤2 mm, moderate if the worst subsidence into the inferior or superior endplate was between 2 to 4 mm, or severe if the worst subsidence into the inferior or superior endplate was ≥4 mm. Results A total of 51 patients (100 levels) were included in this study. A total of 48 levels demonstrated mild subsidence (≤2 mm), 38 demonstrated moderate subsidence (2-4 mm), and 14 demonstrated severe subsidence (≥4 mm). Risk factors for severe subsidence included male gender, multilevel constructs, greater mean vertebral height loss, increased cage height, lower Taillard index, and lower screw tip to vertebral body height ratio. Severe subsidence was not associated with an increased rate of pseudarthrosis. Conclusion Following ACDF with titanium cervical cages, subsidence is an anticipated postoperative occurrence and is not associated with an increased risk of pseudarthrosis.

Study Design: Retrospective cohort study. Objective: Studies investigating the impact of interbody subsidence in ACDF suggest a correlation between subsidence and worse radiographic and patient-reported outcomes. The purpose of this study was to assess whether allograft subsidence assessed on CT is associated with worse cervical alignment. Methods: We performed a retrospective review of a prospective cohort of patients undergoing 1 to 3 level ACDF. Cervical alignment was assessed on standing radiographs performed preoperatively, less than 2 months postoperatively, and greater than 6 months postoperatively. Allograft subsidence was assessed on CT scan performed at least 6 months postoperatively. Patients with at least 1 level demonstrating greater than 4mm of cage subsidence were classified as severe subsidence. Student’s t-test was used to compare all means between groups. Results: We identified 66 patients for inclusion, including 56 patients with non-severe subsidence and 10 patients with severe subsidence. For the entire cohort, there was a significant increase in C2-7 Lordosis (p = 0.005) and Segmental Lordosis (p < 0.00 001) from preoperative to early postoperative. On comparison of severely and non-severely subsided levels, severely subsided levels demonstrated a significantly greater loss of segmental lordosis from early to mid-term follow-up than non-severely subsided levels (-4.89 versus -2.59 degrees, p < 0.0001), manifesting as a significantly lower segmental lordosis at >6 months postoperative (0.54 versus 3.82 degrees, p < 0.00 001). There were no significant differences in global cervical alignment parameters between patients with severe and non-severe subsidence. Conclusions: Severe subsidence is associated with a significant increase in loss of segmental lordosis, but has minimal effect on global cervical alignment parameters.

Study Design: Retrospective Study. Objective: To compare methods of assessing pre-operative bone density to predict risk for osteoporosis related complications (ORC), defined as proximal junctional kyphosis, pseudarthrosis, accelerated adjacent segment disease, reoperation, compression fracture, and instrument failure following spine fusions. Methods: Chart review of primary posterior thoracolumbar or lumbar fusion patients during a 7 year period. Inclusion criteria: preoperative dual-energy x-ray absorptiometry (DXA) test within 1 year and lumbar CT scan within 6 months prior to surgery with minimum of 1 year follow-up. Exclusion criteria: <18 years at time of index procedure, infection, trauma, malignancy, skeletal dysplasia, neuromuscular disorders, or anterior-posterior procedures. Results: 140 patients were included. The average age was 67.9 years, 83 (59.3%) were female, and 45 (32%) had an ORC. There were no significant differences in patient characteristics between those with and without an ORC. Multilevel fusions were associated with ORCs (46.7% vs 26.3%, p = 0.02). Patients with ORCs had lower DXA t-scores (-1.62 vs -1.10, p = 0.003) and average Hounsfield units (HU) (112.1 vs 148.1, p ≤ 0.001). Multivariable binary logistic regression analysis showed lower average HU (Adj. OR 0.00 595% CI 0.0001-0.1713, p = 0.001) was an independent predictor of an ORC. The odds of an ORC increased by 1.7-fold for every 25 point decrease in average HU. Conclusions: The gold standard for assessing bone mineral density has been DXA t-scores, but the best predictor of ORC remains unclear. While both lower t-scores and average HU were associated with ORC, only HU was an independent predictor of ORC.

OBJECTIVE The goal of this study was to compare different recognized definitions of osteoporosis in patients with degenerative lumbar spine pathology undergoing elective spinal fusion surgery to determine which patient population should be considered for preoperative optimization. METHODS A retrospective review of patients in whom lumbar spine surgery was planned at 2 academic medical centers was performed, and the rate of osteoporosis was compared based on different recognized definitions. Assessments were made based on dual-energy x-ray absorptiometry (DXA), CT Hounsfield units (HU), trabecular bone score (TBS), and fracture risk assessment tool (FRAX). The rate of osteoporosis was compared based on different definitions: 1) the WHO definition (T-score ≤ −2.5) at total hip or spine; 2) CT HU of < 110; 3) National Bone Health Alliance (NBHA) guidelines; and 4) “expanded spine” criteria, which includes patients meeting NBHA criteria and/or HU < 110, and/or “degraded” TBS in the setting of an osteopenic T-score. Inclusion criteria were adult patients with a DXA scan of the total hip and/or spine performed within 1 year and a lumbar spine CT scan within 6 months of the physician visit. RESULTS Two hundred forty-four patients were included. The mean age was 68.3 years, with 70.5% female, 96.7% Caucasian, and the mean BMI was 28.8. Fracture history was reported in 53.8% of patients. The proportion of patients identified with osteoporosis on DXA, HUs, NBHA guidelines, and the authors’ proposed “expanded spine” criteria was 25.4%, 36.5%, 75%, and 81.9%, respectively. Of the patients not identified with osteoporosis on DXA, 31.3% had osteoporosis based on HU, 55.1% had osteoporosis with NBHA, and 70.4% had osteoporosis with expanded spine criteria (p < 0.05), with poor correlations among the different assessment tools. CONCLUSIONS Limitations in the use of DXA T-scores alone to diagnose osteoporosis in patients with lumbar spondylosis has prompted interest in additional methods of evaluating bone health in the spine, such as CT HU, TBS, and FRAX, to inform guidelines that aim to reduce fracture risk. However, no current osteoporosis assessment was developed with a focus on improving outcomes in spinal surgery. Therefore, the authors propose an expanded spine definition for osteoporosis to identify a more comprehensive cohort of patients with potential poor bone health who could be considered for preoperative optimization, although further study is needed to validate these results in terms of clinical outcomes.

Study Design: Retrospective cohort study. Objectives: Studies in the lumbar spine suggest a correlation between sarcopenia and worse patient outcomes. The purpose of this study was to determine whether paraspinal Goutalier grade of fat degeneration is associated with patient-reported outcomes in patients undergoing anterior cervical discectomy and fusion (ACDF). Methods: We performed a retrospective review of a prospective cohort of patients undergoing 1- to 3-level ACDF at a single institution between the years 2011-2014. We utilized preoperative magnetic resonance images to classify patients into Goutalier grades. Patient-reported outcomes, including Neck Disability Index (NDI), RAND score, and EQ-5D score were collected and analyzed according to patients’ Goutalier grade. Results: We identified 69 patients for inclusion. A total of 29 patients were classified as Goutalier 0-1 (group 1), 29 were Goutalier 1.5-2 (group 2), and 11 were Goutalier 2.5-4.0 (group 3). All Goutalier groups experienced significant improvement in all 3 outcome scores. Average postoperative NDI scores were 25.3 in group 1, 13.9 in group 2, and 25.1 in group 3 ( P = .02). The percentage of patients in each group reporting worse disability after surgery was 17.2%, 3.3%, and 9.1%, respectively ( P = .05). No statistically significant difference was seen between groups in postoperative EQ-5D ( P = .07) or RAND scores ( P > .05). Conclusions: The present study is the first to assess the association between cervical paraspinal muscle Goutalier grade and patient-reported outcomes following ACDF. Based on our study, patients with worse cervical paraspinal degeneration may benefit from improved symptom relief in comparison to patients with a lesser degree of degeneration undergoing ACDF.