Distance to first symptoms measured by the 6-min walking test differentiates between treatment success and failure in patients with degenerative lumbar disorders

PURPOSE The smartphone-based 6-min walking test (6WT) is an established digital outcome measure in patients undergoing surgery for degenerative lumbar disorders (DLD). In addition to the 6WTs primary outcome measure, the 6-min walking distance (6WD), the patient's distance to first symptoms (DTFS) and time to first symptoms (TTFS) can be recorded. This is the first study to analyse the psychometric properties of the DTFS and TTFS. METHODS Forty-nine consecutive patients (55 ± 15.8 years) completed the 6WT pre- and 6 weeks (W6) postoperative. DTFS and TTFS were assessed for reliability and content validity using disease-specific patient-reported outcome measures. The Zurich Claudication Questionnaire patient satisfaction subscale was used as external criterion for treatment success. Internal and external responsiveness for both measures at W6 was evaluated. RESULTS There was a significant improvement in DTFS and TTFS from baseline to W6 (p < 0.001). Both measures demonstrated a good test-retest reliability (β = 0.86, 95% CI 0.81-0.90 and β = 0.83, 95% CI 0.76-0.87, both p < 0.001). The DTFS exceeded the 6WD capability to differentiate between satisfied (82%) and unsatisfied patients (18%) with an AUC of 0.75 (95% CI 0.53-0.98) vs. 0.70 (95% CI 0.52-0.90). The TTFS did not demonstrate meaningful discriminative abilities. CONCLUSION Change in DTFS can differentiate between satisfied and unsatisfied patients after spine surgery. Digital outcome measures on the 6WT metric provide spine surgeons and researchers with a mean to assess their patient's functional disability and response to surgical treatment in DLD

Association of pre- and postoperative αKlotho levels with long-term remission after pituitary surgery for acromegaly

Soluble αKlotho (sKl) is a disease-specific biomarker that is elevated in patients with acromegaly and declines after surgery for pituitary adenoma. Approximately 25% of patients do not achieve remission after surgery, therefore a risk stratification for patients early in the course of their disease may allow for the identification of patients requiring adjuvant treatment. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) have been assessed as biomarker for disease activity, however the value of sKl as a predictive biomarker of surgical success has not been evaluated yet. In this study, we measured serum biomarkers before and after transsphenoidal pituitary surgery in 55 treatment-naïve patients. Based on biochemical findings at follow-up (7-16 years), we divided patients into three groups: (A) long-term cure (defined by normal IGF-1 and random low GH (< 1 μg/l) or a suppressed GH nadir (< 0.4/μg/l) on oral glucose testing); (B) initial remission with later disease activity; (C) persistent clinical and/or biochemical disease activity. sKl levels positively related to GH, IGF-1 levels and tumor volume. Interestingly, there was a statistically significant difference in pre- and postoperative levels of sKl between the long-term cure group and the group with persistent disease activity. This study provides first evidence that sKl may serve as an additional marker for surgical success, decreasing substantially in all patients with initial clinical remission while remaining high after surgery in patients with persistent disease activity

A T-cell antigen atlas for meningioma: novel options for immunotherapy

Meningiomas are the most common primary intracranial tumors. Although most symptomatic cases can be managed by surgery and/or radiotherapy, a relevant number of patients experience an unfavorable clinical course and additional treatment options are needed. As meningiomas are often perfused by dural branches of the external carotid artery, which is located outside the blood-brain barrier, they might be an accessible target for immunotherapy. However, the landscape of naturally presented tumor antigens in meningioma is unknown. We here provide a T-cell antigen atlas for meningioma by in-depth profiling of the naturally presented immunopeptidome using LC-MS/MS. Candidate target antigens were selected based on a comparative approach using an extensive immunopeptidome data set of normal tissues. Meningioma-exclusive antigens for HLA class I and II are described here for the first time. Top-ranking targets were further functionally characterized by showing their immunogenicity through in vitro T-cell priming assays. Thus, we provide an atlas of meningioma T-cell antigens which will be publicly available for further research. In addition, we have identified novel actionable targets that warrant further investigation as an immunotherapy option for meningioma

Smartphone-Based Self-Assessment of Objective Functional Impairment (6-Minute Walking Test) in Patients Undergoing Epidural Steroid Injection

Epidural steroid injection (ESI) represents a popular treatment option in patients with lumbar degenerative disc disease (DDD). The main objective of the article was to determine whether the 6-minute walking test (6WT) could assist in the discrimination between ESI responders and nonresponders. We used a validated 6WT smartphone application to assess self-measured objective functional impairment (OFI) in 3 patients with DDD undergoing ESI. Patient-reported outcome measures (PROMs), including the Core Outcome Measures Index and the Oswestry Disability Index, were obtained at baseline and at the 3-, 7-, and 28-day follow-up. Descriptive analyses were used to compare PROMs with OFI over time. Two patients responded well to the ESI, illustrated by clinically meaningful improvements in PROMs. This improvement was accompanied by a substantial increase in the 6WT distance (case I: 358 m vs. 517 m and case II: 296 m vs. 625 m). One patient reported only moderate improvement in leg pain and conflicting results in the other PROMs. The 6WT demonstrated a persistent OFI (487 m vs. 488 m). This patient was considered a nonresponder and underwent surgical treatment. This case series illustrates the feasibility of the smartphone-based 6WT as a tool to assess OFI in patients undergoing ESI for lumbar DDD

Longitudinal smartphone-based self-assessment of objective functional impairment in patients undergoing surgery for lumbar degenerative disc disease: initial experience

BACKGROUND: The worldwide spread of smartphone usage enables new possibilities for longitudinal monitoring of objective functional impairment (OFI) in patients undergoing surgery for lumbar degenerative disc disease (DDD). METHODS: Three patients, undergoing elective surgery for lumbar DDD, self-assessed OFI using a recently validated 6-min walking test (6WT) smartphone application. Results are presented as raw 6-min walking distance (6WD) as well as in reference to age- and sex-specific healthy population reference values using standardized z-scores (number of standard deviations). In parallel, patient-reported outcome measures (PROMs), including numeric rating scale (NRS) leg-pain and Core Outcome Measures Index (COMI) were obtained before (pre) and 6 weeks (6 W) as well as 3 months (3 M) after surgery. Descriptive analyses were used to compare PROMs with repeated 6WT measurements over time. The feasibility and benefits of the longitudinal OFI measurements using the 6WT app are discussed. RESULTS: One patient presented a favorable outcome, reflected by a clinically meaningful improvement in PROMs. Correspondingly, the 6WT distance gradually improved above the normal population values ((pre 399 m (z-score - 1.96) vs. 6 W 494 m (- 0.85) vs. 3 M 557 m (- 0.1)). One patient experienced initial improvement at 6 W, followed by a decline in 6WD at 3 M which promoted further interventions with subsequent recovery ((358 m (z-score - 3.29) vs 440 m (- 2.2) vs 431 m (- 2.32) vs 471 m (- 1.78)). The last patient showed a lack of improvement in PROMs as well as in OFI (360 m (z-score 0.0) vs 401 m (0.30) vs 345 m (- 0.11)) resulting in secondary surgery. CONCLUSION: The longitudinal assessment of OFI using the 6WT app was feasible and provided the physician with a detailed history of patients' postoperative walking capacity complementing commonly used PROMs

Normative data of a smartphone app-based 6-minute walking test, test-retest reliability, and content validity with patient-reported outcome measures

OBJECTIVE The 6-minute walking test (6WT) is used to determine restrictions in a subject's 6-minute walking distance (6WD) due to lumbar degenerative disc disease. To facilitate simple and convenient patient self-measurement, a free and reliable smartphone app using Global Positioning System coordinates was previously designed. The authors aimed to determine normative values for app-based 6WD measurements. METHODS The maximum 6WD was determined three times using app-based measurement in a sample of 330 volunteers without previous spine surgery or current spine-related disability, recruited at 8 centers in 5 countries (mean subject age 44.2 years, range 16-91 years; 48.5% male; mean BMI 24.6 kg/m2, range 16.3-40.2 kg/m2; 67.9% working; 14.2% smokers). Subjects provided basic demographic information, including comorbidities and patient-reported outcome measures (PROMs): visual analog scale (VAS) for both low-back and lower-extremity pain, Core Outcome Measures Index (COMI), Zurich Claudication Questionnaire (ZCQ), and subjective walking distance and duration. The authors determined the test-retest reliability across three measurements (intraclass correlation coefficient [ICC], standard error of measurement [SEM], and mean 6WD [95% CI]) stratified for age and sex, and content validity (linear regression coefficients) between 6WD and PROMs. RESULTS The ICC for repeated app-based 6WD measurements was 0.89 (95% CI 0.87-0.91, p < 0.001) and the SEM was 34 meters. The overall mean 6WD was 585.9 meters (95% CI 574.7-597.0 meters), with significant differences across age categories (p < 0.001). The 6WD was on average about 32 meters less in females (570.5 vs 602.2 meters, p = 0.005). There were linear correlations between average 6WD and VAS back pain, VAS leg pain, COMI Back and COMI subscores of pain intensity and disability, ZCQ symptom severity, ZCQ physical function, and ZCQ pain and neuroischemic symptoms subscores, as well as with subjective walking distance and duration, indicating that subjects with higher pain, higher disability, and lower subjective walking capacity had significantly lower 6WD (all p < 0.001). CONCLUSIONS This study provides normative data for app-based 6WD measurements in a multicenter sample from 8 institutions and 5 countries. These values can now be used as reference to compare 6WT results and quantify objective functional impairment in patients with degenerative diseases of the spine using z-scores. The authors found a good to excellent test-retest reliability of the 6WT app, a low area of uncertainty, and high content validity of the average 6WD with commonly used PROMs