Background and purpose

Pulsatile tinnitus (PT) is the subjective sensation of a pulse-synchronous sound, most often due to a cerebrovascular etiology. PT can severely impact quality of life and may indicate a life-threatening process, yet a timely and accurate diagnosis can often lead to effective treatment. Clinical assessment with a history and physical examination can often suggest a diagnosis for PT, but is rarely definitive. Therefore, PT should be evaluated with a comprehensive and targeted radiographic imaging protocol. MR imaging provides a safe and effective means to evaluate PT. Specific MR sequences may be used to highlight different elements of cerebrovascular anatomy and physiology. However, routine MR evaluation of PT must comply with economic and practical constraints, while effectively capturing both common and rarer, life-threatening etiologies of PT.

Methods

In this state-of-the-art review, we describe our institutional MR protocol for evaluating PT.

Results

This protocol includes the following dedicated sequences: time-of-flight magnetic resonance angiography; arterial spin labeling; spoiled gradient recalled acquisition in the steady state; time-resolved imaging of contrast kinetics; diffusion weighted imaging, and 3-dimensional fluid-attenuated inversion recovery.

Conclusions

We describe the physiologic and clinical rationale for including each MR sequence in a comprehensive PT imaging protocol, and detail the role of MR within the broader evaluation of PT, from clinical presentation to treatment.

Purpose

To develop a model for factors predictive of Post-Acute Care Facility (PACF) discharge in adult patients undergoing elective multi-level (≥ 3 segments) lumbar/thoracolumbar spinal instrumented fusions.

Methods

The State Inpatient Databases acquired from the Healthcare Cost and Utilization Project from 2005 to 2013 were queried for adult patients who underwent elective multi-level thoracolumbar fusions for spinal deformity. Outcome variables were classified as discharge to home or PACF. Predictive variables included demographic, pre-operative, and operative factors. Univariate and multivariate logistic regression analyses informed development of a logistic regression-based predictive model using seven selected variables. Performance metrics included area under the curve (AUC), sensitivity, and specificity.

Results

Included for analysis were 8866 patients. The logistic model including significant variables from multivariate analysis yielded an AUC of 0.75. Stepwise logistic regression was used to simplify the model and assess number of variables needed to reach peak AUC, which included seven selected predictors (insurance, interspaces fused, gender, age, surgical region, CCI, and revision surgery) and had an AUC of 0.74. Model cut-off for predictive PACF discharge was 0.41, yielding a sensitivity of 75% and specificity of 59%.

Conclusions

The seven variables associated significantly with PACF discharge (age > 60, female gender, non-private insurance, primary operations, instrumented fusion involving 8+ interspaces, thoracolumbar region, and higher CCI scores) may aid in identification of adults at risk for discharge to a PACF following elective multi-level lumbar/thoracolumbar spinal fusions for spinal deformity. This may in turn inform discharge planning and expectation management.

Introduction

The purpose of this study is to provide a state-of-the-art review regarding risk factors for perioperative complications in adult spinal deformity (ASD) surgery. The review includes levels of evidence for risk factors associated with complications in ASD surgery.

Methods

Using the PubMed database, we searched for complications, risk factors, and adult spinal deformity. The included publications were assessed for level of evidence as described in clinical practice guidelines published by the North American Spine Society, with summary statements generated for each risk factor (Bono et al. in Spine J 9:1046-1051, 2009).

Results

Frailty had good evidence (Grade A) as a risk for complications in ASD patients. Fair evidence (Grade B) was assigned for bone quality, smoking, hyperglycemia and diabetes, nutritional status, immunosuppression/steroid use, cardiovascular disease, pulmonary disease, and renal disease. Indeterminate evidence (Grade I) was assigned for pre-operative cognitive function, mental health, social support, and opioid utilization.

Conclusions

Identification of risk factors for perioperative complications in ASD surgery is a priority for empowering informed choices for patients and surgeons and managing patient expectations. Risk factors with grade A and B evidence should be identified prior to elective surgery and modified to reduce the risk of perioperative complications.

Introduction

Adjacent segment disease (ASD) of the cervical spine is a common disabling phenomenon that often requires surgical intervention. The goal of this study was to evaluate the economic impact of revision operations for cervical ASD.

Methods

Consecutive adults who underwent revision cervical spine surgery for ASD at a single institution between 2014 and 2017 were retrospectively reviewed. Direct costs were identified from medical billing data and calculated for each revision surgery for ASD. Incomplete cost data for revision operations were used as a criterion for exclusion. Cost data were stratified based on the approach of the index and revision operations.

Results

Eighty-five patients (average age 57 ± 10 years) underwent revisions for cervical ASD, which summed to $2 million (average $23,702). Revisions consisted of 45 anterior operations (anterior cervical diskectomy and fusion, 34; corpectomy, 10; and cervical disk arthroplasty, 1), 32 posterior operations (posterior cervical fusion, 14; foraminotomy, 14; and laminoplasty, 4), and 8 circumferential operations. Circumferential revisions had notably higher average direct costs ($57,376) than single approaches (anterior, $20,084 and posterior, $20,371). Of posterior revisions, foraminotomies had the lowest average direct costs ($5,389), whereas posterior cervical fusion had the highest average direct costs ($35,950). Of anterior revisions, corpectomies ($30,265) had notably greater average direct costs than anterior cervical diskectomy and fusion ($17,514). Costs were not notably different for revision approaches based on the index operations' approach.

Discussion

Revision operations for cervical ASD are highly heterogeneous and associated with an average direct cost of $27,702. Over 3 years, revisions for 85 patients with cervical ASD represented a notable economic expense (greater than $2.0 million).

Data availability

Deidentified data may be provided by request to the corresponding author.

Background

While genetic alterations in brain metastases (BMs) have been previously explored, there are limited data examining their association with recurrence after surgical resection. This study aimed to identify genetic alterations within BMs associated with CNS recurrence after surgery across multiple cancer types.

Methods

A retrospective, single-center study was conducted with patients who underwent resection of a BM with available clinical and gene sequencing data available. Local and remote CNS recurrence were the primary study outcomes. Next-generation sequencing of the coding regions in over 500 oncogenes was performed in brain metastasis specimens. Cox proportional hazards analyses were performed to identify clinical features and genomic alterations associated with CNS recurrence.

Results

A total of 90 patients undergoing resection of 91 BMs composed the cohort. Genes most frequently mutated in the cohort included TP53 (64%), CDKN2A (37%), TERT (29%), CDKN2B (23%), NF1 (14%), KRAS (14%), and PTEN (13%), all of which occurred across multiple cancer types. CDKN2A/B co-deletion was seen in 21 (23.1%) brain metastases across multiple cancer types. In multivariate Cox proportional hazard analyses including patient, tumor, and treatment factors, CDKN2A/B co-deletion in the brain metastasis was associated with increased risk of local (HR 4.07, 95% CI 1.32-12.54, P = 0.014) and remote (HR 2.28, 95% CI 1.11-4.69, P = 0.025) CNS progression. Median survival and length of follow-up were not different based on CDKN2A/B mutation status.

Conclusions

CDKN2A/B co-deletion detected in BMs is associated with increased CNS recurrence after surgical resection. Additional work is needed to determine whether more aggressive treatment in patients with this mutation may improve outcomes.

Objective

Meningiomas are the most common primary intracranial tumor, and resection is a mainstay of treatment. It is unclear what duration of imaging follow-up is reasonable for WHO grade I meningiomas undergoing complete resection. This study examined recurrence rates, timing of recurrence, and risk factors for recurrence in patients undergoing a complete resection (as defined by both postoperative MRI and intraoperative impression) of WHO grade I meningiomas.

Methods

The authors conducted a retrospective, single-center study examining recurrence risk for adult patients with a single intracranial meningioma that underwent complete resection. Uni- and multivariate nominal logistic regression and Cox proportional hazards analyses were performed to identify variables associated with recurrence and time to recurrence. Two supervised machine learning algorithms were then implemented to confirm factors within the cohort that were associated with recurrence.

Results

The cohort consisted of 823 patients who met inclusion criteria, and 56 patients (6.8%) had recurrence on imaging follow-up. The median age of the cohort was 56 years, and 77.4% of patients were female. The median duration of head imaging follow-up for the entire cohort was 2.7 years, but for the subgroup of patients who had a recurrence, the median follow-up was 10.1 years. Estimated 1-, 5-, 10-, and 15-year recurrence-free survival rates were 99.8% (95% confidence interval [CI] 98.8%-99.9%), 91.0% (95% CI 87.7%-93.6%), 83.6% (95% CI 78.6%-87.6%), and 77.3% (95% CI 69.7%-83.4%), respectively, for the entire cohort. On multivariate analysis, MIB-1 index (odds ratio [OR] per 1% increase: 1.34, 95% CI 1.13-1.58, p = 0.0003) and follow-up duration (OR per year: 1.12, 95% CI 1.03-1.21, p = 0.012) were both associated with recurrence. Gradient-boosted decision tree and random forest analyses both identified MIB-1 index as the main factor associated with recurrence, aside from length of imaging follow-up. For tumors with an MIB-1 index < 8, recurrences were documented up to 8 years after surgery. For tumors with an MIB-1 index ≥ 8, recurrences were documented up to 12 years following surgery.

Conclusions

Long-term imaging follow-up is important even after a complete resection of a meningioma. Higher MIB-1 labeling index is associated with greater risk of recurrence. Imaging screening for at least 8 years in patients with an MIB-1 index < 8 and at least 12 years for those with an MIB-1 index ≥ 8 may be needed to detect long-term recurrences.

Early diagnosis of psoriatic arthritis (PSA) is important for successful therapeutic intervention but currently remains challenging due, in part, to the scarcity of non-invasive biomarkers. In this study, we performed single cell profiling of transcriptome and cell surface protein expression to compare the peripheral blood immunocyte populations of individuals with PSA, individuals with cutaneous psoriasis (PSO) alone, and healthy individuals. We identified genes and proteins differentially expressed between PSA, PSO, and healthy subjects across 30 immune cell types and observed that some cell types, as well as specific phenotypic subsets of cells, differed in abundance between these cohorts. Cell type-specific gene and protein expression differences between PSA, PSO, and healthy groups, along with 200 previously published genetic risk factors for PSA, were further used to perform machine learning classification, with the best models achieving AUROC ≥ 0.87 when either classifying subjects among the three groups or specifically distinguishing PSA from PSO. Our findings thus expand the repertoire of gene, protein, and cellular biomarkers relevant to PSA and demonstrate the utility of machine learning-based diagnostics for this disease.

The IL-17A inhibitor secukinumab is efficacious for the treatment of psoriasis. To better understand its mechanism of action, we investigated its impact on psoriatic lesions from 15 patients with moderate-to-severe plaque psoriasis undergoing secukinumab treatment. We characterized the longitudinal transcriptomic changes of whole lesional skin tissue as well as cutaneous CD4⁺ and CD8⁺ T effector cells and CD4⁺ T regulatory cells across 12 weeks of treatment. Secukinumab was clinically effective and reduced disease-associated overexpression of IL17A , IL17F, IL23A, IL23R, and IFNG in whole tissue as soon as 2 weeks after initiation of treatment. IL17A overexpression in T-cell subsets, primarily CD8⁺ T cells, was also reduced. Although secukinumab treatment resolved 89‒97% of psoriasis-associated expression differences in bulk tissue and T-cell subsets by week 12 of treatment, we observed expression differences involved in IFN signaling and metallothionein synthesis that remained unresolved at this time point as well as potential treatment-associated expression differences involved in IL-15 signaling. These changes were accompanied by shifts in broader immune cell composition on the basis of deconvolution of RNA-sequencing data. In conclusion, our study reveals several phenotypic and cellular changes within the lesion that underlie clinical improvement from secukinumab.