Role of microsurgical tumor burden reduction in patients with breast cancer brain metastases considering molecular subtypes: a two-center volumetric survival analysis.

BACKGROUND: Advancements in metastatic breast cancer (BC) treatment have enhanced overall survival (OS), leading to increased rates of brain metastases (BM). This study analyzes the association between microsurgical tumor reduction and OS in patients with BCBM, considering tumor molecular subtypes and perioperative treatment approaches. METHODS: Retrospective analysis of surgically treated patients with BCBM from two tertiary brain tumor Swiss centers. The association of extent of resection (EOR), gross-total resection (GTR) achievement, and postoperative residual tumor volume (RV) with OS and intracranial progression-free survival (IC-PFS) was evaluated using Cox proportional hazard model. RESULTS: 101 patients were included in the final analysis, most patients (38%) exhibited HER2-/HR + BC molecular subtype, followed by HER2 + /HR + (25%), HER2-/HR- (21%), and HER2 + /HR- subtypes (13%). The majority received postoperative systemic treatment (75%) and radiotherapy (84%). Median OS and intracranial PFS were 22 and 8 months, respectively. The mean pre-surgery intracranial tumor volume was 26 cm3, reduced to 3 cm3 post-surgery. EOR, GTR achievement and RV were not significantly associated with OS or IC-PFS, but higher EOR and lower RV correlated with extended OS in patients without extracranial metastases. HER2-positive tumor status was associated with longer OS, extracranial metastases at BM diagnosis and symptomatic lesions with shorter OS and IC-PFS. CONCLUSIONS: Our study found that BC molecular subtypes, extracranial disease status, and BM-related symptoms were associated with OS in surgically treated patients with BCBM. Additionally, while extensive resection to minimize residual tumor volume did not significantly affect OS across the entire cohort, it appeared beneficial for patients without extracranial metastases.

Multiple craniotomies in patients with brain metastases: a two-center, propensity score-matched study.

The current study addresses the question of whether the resection of more than one BM by multiple craniotomies within the same operation is associated with more adverse events (AEs) and worse functional outcome compared to cases in which only one BM was resected. All patients who underwent more than one craniotomy for resection of multiple BM at two Swiss tertiary neurosurgical care centers were included. Any AEs, functional outcome, and overall survival (OS) were analyzed after 1:1 propensity score matching with patients who underwent removal of a single BM only. A total of 94 patients were included in the final study cohort (47 of whom underwent multiple craniotomies). There was no significant difference in the incidence of AEs between the single and the multiple craniotomy group (n = 2 (4.3%) vs. n = 4 (8.5%), p = .7). Change in modified Rankin Scale (mRS) and Karnofsky Performance Status (KPS) at discharge demonstrated that slightly more single craniotomy patients improved in mRS, while the proportion of patients who worsened in mRS (16.3 vs. 16.7%) and KPS (13.6 vs. 15.2%) was similar in both groups (p = .42 for mRS and p = .92 for KPS). Survival analysis showed no significant differences in OS between patients with single and multiple craniotomies (p = .18). Resection of multiple BM with more than one craniotomy may be considered a safe option without increased AEs or worse functional outcome.

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.

Symptom Burden in Glioblastoma: A Prospective Pilot Study from Diagnosis to First Progression.

INTRODUCTION: The evaluation of symptom burden, performance status, and neurological function is still challenging in glioblastoma (GBM) patients. Patients may suffer from a wide spectrum of neurological symptoms like cognitive deficits, aphasia, or hemiparesis, which interfere to report to comprehensive questionnaires. However, an integrated and reliable neuro-oncological assessment is the key in the clinical management and in the evaluation of treatment benefits for GBM patients. METHODS: We implemented an easy-to-use clinical toolkit for the prospective assessment and follow-up evaluation of GBM patients using the Karnofsky performance status (KPS), the National Institute of Health Stroke Scale (NIH-SS), and simple scores for the evaluation of key symptoms like fatigue, depression, and headache. RESULTS: We prospectively followed 50 patients. The composite score (headache, depression, and fatigue), fatigue alone, the NIHSS, and the KPS were suitable biomarkers to evaluate symptom burden in GBM patients and indicate clinical disease progression. DISCUSSION/CONCLUSION: The proposed clinical toolkit seems feasible in routine clinical practice and reflects changes in symptom burden in different stages of the postsurgical course of GBM patients in this monocentric clinical pilot trial.

Successful weaning versus permanent cerebrospinal fluid diversion after aneurysmal subarachnoid hemorrhage: post hoc analysis of a Swiss multicenter study.

OBJECTIVE: Acute hydrocephalus is a frequent complication after aneurysmal subarachnoid hemorrhage (aSAH). Among patients needing CSF diversion, some cannot be weaned. Little is known about the comparative neurological, neuropsychological, and health-related quality-of-life (HRQOL) outcomes in patients with successful and unsuccessful CSF weaning. The authors aimed to assess outcomes of patients by comparing those with successful and unsuccessful CSF weaning; the latter was defined as occurring in patients with permanent CSF diversion at 3 months post-aSAH. METHODS: The authors included prospectively recruited alert (i.e., Glasgow Coma Scale score 13-15) patients with aSAH in this retrospective study from six Swiss neurovascular centers. Patients underwent serial neurological (National Institutes of Health Stroke Scale), neuropsychological (Montreal Cognitive Assessment), disability (modified Rankin Scale), and HRQOL (EuroQol-5D) examinations at < 72 hours, 14-28 days, and 3 months post-aSAH. RESULTS: Of 126 included patients, 54 (42.9%) developed acute hydrocephalus needing CSF diversion, of whom 37 (68.5%) could be successfully weaned and 17 (31.5%) required permanent CSF diversion. Patients with unsuccessful weaning were older (64.5 vs 50.8 years, p = 0.003) and had a higher rate of intraventricular hemorrhage (52.9% vs 24.3%, p = 0.04). Patients who succeed in restoration of physiological CSF dynamics improve on average by 2 points on the Montreal Cognitive Assessment between 48-72 hours and 14-28 days, whereas those in whom weaning fails worsen by 4 points (adjusted coefficient 6.80, 95% CI 1.57-12.04, p = 0.01). They show better neuropsychological recovery between 48-72 hours and 3 months, compared to patients in whom weaning fails (adjusted coefficient 7.60, 95% CI 3.09-12.11, p = 0.02). Patients who receive permanent CSF diversion (ventriculoperitoneal shunt) show significant neuropsychological improvement thereafter, catching up the delay in neuropsychological improvement between 14-28 days and 3 months post-aSAH. Neurological, disability, and HRQOL outcomes at 3 months were similar. CONCLUSIONS: These results show a temporary but clinically meaningful cognitive benefit in the first weeks after aSAH in successfully weaned patients. The resolution of this difference over time may be due to the positive effects of permanent CSF diversion and underlines its importance. Patients who do not show progressive neuropsychological improvement after weaning should be considered for repeat CT imaging to rule out chronic (untreated) hydrocephalus.

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 (ß = 0.86, 95% CI 0.81-0.90 and ß = 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.

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.

Objective outcome measures may demonstrate continued change in functional recovery in patients with ceiling effects of subjective patient-reported outcome measures after surgery for lumbar degenerative disorders.

BACKGROUND CONTEXT: The 6-minute walking test (6WT) has been previously shown to be a reliable and valid outcome measure. It is unclear if the 6WT may further help to detect differences in well performing patients that reach a ceiling effect in PROMs after surgery. PURPOSE: To evaluate changes and timing of change in objective functional impairment (OFI) as measured with the smartphone-based 6WT in relation to patient-reported outcome measures (PROMs) after surgery for degenerative lumbar disorders (DLD). STUDY DESIGN: Prospective observational cohort study. PATIENT SAMPLE: Fifty consecutive patients undergoing surgery for DLD. OUTCOME MEASURES: Patients self-determined their OFI using the 6WT application (6WT-app) and completed a set of paper-based PROMs before, 6 weeks and 3 months after surgery. METHODS: Fifty patients undergoing surgery for DLD were assessed preoperatively (baseline), 6 weeks (6W) and 3 months (3M) postoperatively. Paired sample t-tests were used to establish significant changes in raw 6-minute walking distance (6WD) and standardized Z-scores, as well as PROMs. Pearson correlation coefficient was used to define the relationship between 6WT and PROMs. Floor and ceiling effects were assessed for each PROM (visual analogue scale [VAS], core outcome measure index [COMI], Zurich claudication questionnaire [ZCQ]). RESULTS: Mean 6WT results improved from 377 m (standard deviation - SD 137; Z-score: 1.8, SD 1.8) to 490 m (SD 126; -0.7, SD 1.5) and 518 m (SD 112; -0.4, SD 1.41; all p<.05) at 6W and 3M follow-up. No significant improvement was observed between 6W and 3M for the ZCQ, VAS back and leg pain. While correlation between 6WT and all PROMs were weak at baseline, correlation coefficient increased to moderate at 3M. A considerable ceiling effect (best possible score) was observed, most notably for the ZCQ physical performance, VAS back and leg pain in 24%, 20%, and 16% of patient at 6W and in 30%, 24%, and 28% at 3M. CONCLUSIONS: Objective functional tests can describe the continued change in the physical recovery of a patient and may help to detect differences in well performing groups as well as in cases where patients' PROM results cannot further improve because of a ceiling effect.

Gender disparity in neurosurgery: A multinational survey on gender-related career satisfaction.

Introduction: Women continue to be underrepresented in the majority of surgical specialties, including neurosurgery. Research question: In this multinational survey, we aimed to assess current gender disparities in neurosurgery focusing on job satisfaction and inequity/discrimination at work. Material and methods: Female and male members of the European Association of Neurosurgical Societies were asked to complete an electronic survey (Google Forms, Mountain View) containing demographic baseline data and questions on attitudes regarding gender disparity, personal experience with gender inequity and career satisfaction/work-life balance. Quantitative analyses were performed to analyse the responses, including summary and comparative statistics. Results: We received 168 responses from 40 different countries. Survey responders had a mean age of 40.8 â€‹± â€‹11.5 years; 29.8% were female. There were significant more male than female residents and attending surgeons per department. Eighty-eight percent of female and 38.1% of male responders experienced gender inequity or discrimination at work (adjusted OR 10.8, 95%CI 4.2-27.8, p<0.001). Female neurosurgeons were more likely to be discriminated by colleagues (aOR 4.32, 95%CI 2.1-9.1, p<0.001) and by patients/relatives (aOR 3.65, 95%CI 1.77-7.54, p<0.001). There was a trend towards lower job satisfaction (p=0.012), less satisfaction with career goals (p=0.035) and worse work-life balance (p=0.0021) in female surgeons. Discussion and conclusion: This survey underlines that a significant proportion of neurosurgeons - in particular females - continue to experience gender inequity & discrimination at work, which may translate into lower work-related satisfaction. A better understanding of the gender-related aspects of job satisfaction is an important step to improving gender equity in our profession.

Smartphone-based real-life activity data for physical performance outcome in comparison to conventional subjective and objective outcome measures after degenerative lumbar spine surgery.

Introduction: Outcome assessments after surgery for degenerative lumbar disorders (DLDs) rely on subjective patient-reported outcomes (PROMs). New objective functional capacity tests, like the smartphone-based 6-min walking test (6WT), have been introduced but presumably also do not reflect the patient's real-life functional performance. Research question: Pilot study to analyze changes in smartphone-based real-life activity data for physical performance outcome in patients undergoing surgery for DLD. Material and methods: Prospective observational study of DLD patients. Objective functional capacity and subjective outcomes were measured using 6WT and PROMs. Real-life physical performance data were acquired retrospectively using Apple iPhone Health data and compared against objective capacity and subjective outcomes. Results: Eight patients (mean 46 years, 62% male) provided 286.858 smartphone mile counts. PROMs and physical capacity (6WT) significantly improved postoperatively. 6WT results increased from 352m pre-to 555/567m at 6/12 weeks postoperatively (p â€‹= â€‹0.03). For physical performance a linear mixed effect models showed an increase in daily distance in the first 4 months after surgery (slope +0.178; p â€‹< â€‹0.001). However, those increases reversed from 4 until 12 months postoperatively (negative slope estimate of -0.076; p â€‹< â€‹0.001). Smartphone-derived physical performance measures showed a positive correlation with corresponding physical capacity in the 6WT (R â€‹= â€‹0.57,p â€‹= â€‹0.004) and negative correlations with PROMs (COMI: R â€‹= â€‹-0.62p â€‹= â€‹0.001; ZCQ-Physical-Function: R â€‹= â€‹-0.68,p â€‹< â€‹0.001; ZCQ-Symptom-Severity: R â€‹= â€‹-0.52,p â€‹= â€‹0.009). Discussion and conclusion: Smartphone-based real-life activity data allows for longitudinal physical performance assessment. Physical performance correlated with physical capacity and patient's subjective perception of disability. However, physical performance may be more resistant to postoperative longtime change which should consult a more cautious use as objective outcome measure.

External Validation of the Minimum Clinically Important Difference in the Timed-up-and-go Test After Surgery for Lumbar Degenerative Disc Disease.

STUDY DESIGN: Prospective observational cohort study. OBJECTIVE: The aim of this study was to provide external validation of the minimum clinically important difference (MCID) of the Timed-up-and-go (TUG) test. SUMMARY OF BACKGROUND DATA: The TUG test is one of the best explored and most frequently applied objective task-based functional outcome measure in patients with lumbar degenerative disc disease (DDD). The increased use of the TUG test is based on its solid psychometric properties; however, an external validation of the originally determined MCID is lacking. METHODS: Forty-nine patients with lumbar DDD, scheduled for elective spine surgery, were assessed pre- and 6-weeks (W6) postoperative. MCID values were calculate for raw TUG test times (seconds) and standardized TUG z scores using three different computation methods and the following established patient-reported outcome measures (PROMs) as anchors: Visual Analog Scales (VAS), Core Outcome Measures Index Back, Zurich Claudication Questionnaire (ZCQ). RESULTS: The three computation methods generated a range of MCID values, depending on the PROM used as anchor, from 0.9 s (z score of 0.3) based on the VAS leg pain to 3.0 seconds (z score of 2.7) based on the ZCQ physical function scale. The average MCID of the TUG test across all anchors and computation methods was 2.1 s (z score of 1.5). According to the average MCID of raw TUG test values or TUG z scores, 41% and 43% of patients classified as W6 responders to surgery, respectively. CONCLUSION: This study confirms the ordinally reported TUG MCID values in patients undergoing surgery for lumbar. A TUG test time change of 2.1 seconds (or TUG z score change of 1.5) indicates an objective and clinically meaningful change in functional status. This report facilitates the interpretation of TUG test results in clinical routine as well as in research.Level of Evidence: 3.

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.

Assessment of neurological function using the National Institute of Health Stroke Scale in patients with gliomas.

BACKGROUND: The evaluation of treatment response in patients with gliomas is performed using the Response Assessment in Neuro-Oncology (RANO) criteria. These criteria are based on cerebral magnetic resonance imaging (MRI), steroid use, and neurological function. However, a standardized tool for evaluating neurological function was lacking. We compared changes in the National Institute of Health Stroke Scale (NIHSS) to changes in the RANO categories to determine the relationship between clinical and neuroradiological findings. METHODS: We reviewed data on all adult patients with supratentorial gliomas WHO grade II-IV who were treated at the Cantonal Hospital St. Gallen from 2008 to 2015. The NIHSS was performed prospectively at baseline and at 3-month intervals simultaneously to MRI. Associations between changes in the NIHSS and RANO categories were assessed using the Stuart-Maxwell test. RESULTS: Our cohort consisted of 61 patients from which 471 observations were analyzed. The most common histological diagnosis was glioblastoma (49.2%). In total, 74% of RANO categories and 81% of the NIHSS scores remained stable on follow-up. Statistically, contemporaneous changes in the RANO category did not correlate with changes in the NIHSS (P < .0001). CONCLUSION: The application of the NIHSS is easy and feasible in the heterogeneous population of glioma patients. In our cohort, the RANO categories did not reflect contemporaneous changes in the NIHSS. A validated clinical outcome measure with a well-defined minimal clinically important difference is warranted in neuro-oncological research and clinical practice.

Patients undergoing surgery for lumbar degenerative spinal disorders favor smartphone-based objective self-assessment over paper-based patient-reported outcome measures.

BACKGROUND CONTEXT: Smartphone-based applications enable new prospects to monitor symptoms and assess functional outcome in patients with lumbar degenerative spinal disorders. However, little is known regarding patient acceptance and preference towards new modes of digital objective outcome assessment. PURPOSE: To assess patient preference of an objective smartphone-based outcome measure compared to conventional paper-based subjective methods of outcome assessment. STUDY DESIGN: Prospective observational cohort study. PATIENT SAMPLE: Fourty-nine consecutive patients undergoing surgery for lumbar degenerative spinal disorder. OUTCOME MEASURES: Patients completed a preference survey to assess different methods of outcome assessment. A 5-level Likert scale ranged from strong disagreement (2 points) over neutral (6 points) to strong agreement (10 points) was used. METHODS: Patients self-determined their objective functional impairment using the 6-minute Walking Test application (6WT-app) and completed a set of paper-based patient-reported outcome measures (PROMs) before and 6 weeks after surgery. Patients were then asked to rate the methods of outcome assessment in terms of suitability, convenience, and responsiveness to their symptoms. RESULTS: The majority of patients considered the 6WT-app a suitable instrument (median 8.0, interquartile range [IQR] 4.0). Patients found the 6WT more convenient (median 10.0, IQR 2.0) than the Zurich Claudication Questionnaire (ZCQ; median 8.0, IQR 4.0, p=.019) and Core Outcome Measure Index (COMI; median 8.0, IQR 4.0, p=.007). There was good agreement that the 6WT-app detects change in physical performance (8.0, IQR 4.0). 78 % of patients considered the 6WT superior in detecting differences in symptoms (vs. 22% for PROMs). Seventy-six percent of patients would select the 6WT over the other, 18% the ZCQ and 6% the COMI. Eighty-two percent of patients indicated their preference to use a smartphone app for the assessment and monitoring of their spine-related symptoms in the future. CONCLUSIONS: Patients included in this study favored the smartphone-based evaluation of objective functional impairment over paper-based PROMs. Involving patients more actively by means of digital technology may increase patient compliance and satisfaction as well as diagnostic accuracy.

Assessment of the Minimum Clinically Important Difference in the Smartphone-based 6-minute Walking Test After Surgery for Lumbar Degenerative Disc Disease.

STUDY DESIGN: Prospective cohort study. OBJECTIVE: The aim of this study was to determine the minimum clinically important difference (MCID) of the 6-minute walking test (6WT) after surgery for lumbar degenerative disc disease (DDD). SUMMARY OF BACKGROUND DATA: The smartphone-based 6WT is a valid and reliable tool to quantify objective functional impairment in patients with lumbar DDD. To date, the MCID of the 6WT has not been described in patients with DDD. METHODS: We assessed patients pre- and 6-weeks postoperatively, analyzing both raw 6-minute walking distances (6WD; in meters) and standardized 6WT z scores. Three methods were applied to compute MCID values using established patient-reported outcomes measures (PROMs) as anchors (VAS back/leg pain, Zurich Claudication Questionnaire [ZCQ], Core Outcome Measures Index [COMI]): average change, minimum detectable change, and the change difference approach. RESULT: We studied 49 patients (59% male) with a mean age of 55.5 ±â€Š15.8 years. The computation methods revealed MCID values ranging from 81 m (z score of 0.9) based on the VAS back pain to 99 m (z score of 1.0) based on the ZCQ physical function scale. The average MCID of the 6WT was 92 m (z score of 1.0). Based on the average MCID of raw 6WD values or standardized z scores, 53% or 49% of patients classified as 6-week responders to surgery for lumbar DDD, respectively. CONCLUSION: The MCID for the 6WT in lumbar DDD patients is variable, depending on the calculation technique. We propose a MCID of 92m (z score of 1.0), based on the average of all three methods. Using a z score as MCID allows for the standardization of clinically meaningful change and attenuates age- and sex-related differences.Level of Evidence: 3.

Responsiveness of the self-measured 6-minute walking test and the Timed Up and Go test in patients with degenerative lumbar disorders.

OBJECTIVE: The 6-minute walking test (6WT) and the Timed Up and Go (TUG) test are two of the most commonly applied standardized measures of objective functional impairment that help support clinical decision-making for patients undergoing surgery for degenerative lumbar disorders. This study correlates smartphone-app-based 6WT and TUG results to evaluate their responsiveness. METHODS: In a prospective study, 49 consecutive patients were assessed preoperatively and 6 weeks postoperatively using the 6WT, the TUG test, and commonly used patient-reported outcome measures. Raw values and standardized z-scores of both objective tests were correlated. An external criterion for treatment success was created based on the Zurich Claudication Questionnaire patient satisfaction subscale. Internal and external responsiveness for both functional tests was evaluated. RESULTS: The mean preoperative 6WT results improved from 401 m (SD 129 m), z-score -1.65 (SD 1.6) to 495 m (SD 129 m), z-score -0.71 (SD 1.6, p < 0.001). The mean preoperative TUG test results improved from 10.44 seconds (SD 4.37, z-score: -3.22) to 8.47 seconds (SD 3.38, z-score: -1.93, p < 0.001). The 6WT showed a strong negative correlation with TUG test results (r = -66, 95% CI 0.76-0.53, p < 0.001). The 6WT showed higher internal responsiveness (standardized responsive mean = 0.86) compared to the TUG test (standardized responsive mean = 0.67). Evaluation of external responsiveness revealed that the 6WT was capable of differentiating between patients who were satisfied and those who were unsatisfied with their treatment results (area under the curve = 0.70), whereas this was not evident for the TUG test ( area under the curve = 0.53). CONCLUSIONS: Both tests adequately quantified functional impairment in surgical candidates with degenerative lumbar disorders. The 6WT demonstrated better internal and external responsiveness compared with the TUG test. Clinical trial registration no.: NCT03977961 (clinicaltrials.gov). ABBREVIATIONS: AUC = area under the curve; COMI = Core Outcome Measures Index; DLDs = degenerative lumbar disorders; LDH = lumbar disc herniation; LSS = lumbar spinal stenosis; PROM = patient-reported outcome measure; ROC = receiver operating characteristic; SRM = standardized responsive mean; TUG = Timed Up and Go; VAS = visual analog scale; 6WD = 6-minute walking distance; 6WT = 6-minute walking test; ZCQ = Zurich Claudication Questionnaire.

External Validation of the Timed Up and Go Test as Measure of Objective Functional Impairment in Patients With Lumbar Degenerative Disc Disease.

BACKGROUND: The Timed Up and Go (TUG) test is the most commonly applied objective measure of functional impairment in patients with lumbar degenerative disc disease (DDD). OBJECTIVE: To demonstrate external content validity of the TUG test. METHODS: Consecutive adult patients, scheduled for elective lumbar spine surgery, were screened for enrollment into a prospective observational study. Disease severity was estimated by patient-reported outcome measures (PROMs; Visual Analog Scales [VAS], Core Outcome Measures Index [COMI] back, Zurich Claudication Questionnaire [ZCQ]) and the TUG test. Pearson correlation coefficients (PCCs) were used to describe the relationship between logarithmic TUG test raw values and PROMs. RESULTS: A total of 70 patients (mean age 55.9 ± 15.4 yr; 38.6% female; 27.1% previous spine surgery; 28.6% lower extremity motor deficits) with lumbar disc herniation (50%), lumbar spinal stenosis (34.3%), or instability requiring spinal fusion (15.7%) were included. The mean TUG test time was 10.8 ± 4.4 s; age- and sex-adjusted objective functional impairment (OFI) T-score was 134.2 ± 36.9. A total of 12 (17.1%) patients had mild, 14 (20%) moderate, and 9 (12.9%) severe OFI, while 35 (50%) had TUG test results within the normal population range (no OFI). PCCs between TUG test time and VAS back pain were r = 0.37 (P = .002), VAS leg pain r = 0.37 (P = .002), COMI back r = 0.50 (P < .001), ZCQ symptom severity r = 0.41 (P < .001), and ZCQ physical function r = 0.36 (P = .002). CONCLUSION: This external validation demonstrated similar OFI rates and PCCs between logarithmic TUG test results and PROMs compared to the original article from 2016. These findings support the TUG test being a quick, easy-to-use objective test, which provides the physician with a robust estimate of pain and functional impairment.

The association of patient age with postoperative morbidity and mortality following resection of intracranial tumors.

Introduction: The postoperative functional status of patients with intracranial tumors is influenced by patient-specific factors, including age. Research question: This study aimed to elucidate the association between age and postoperative morbidity or mortality following the resection of brain tumors. Material and methods: A multicenter database was retrospectively reviewed. Functional status was assessed before and 3-6 months after tumor resection by the Karnofsky Performance Scale (KPS). Uni- and multivariable linear regression were used to estimate the association of age with postoperative change in KPS. Logistic regression models for a ≥10-point decline in KPS or mortality were built for patients ≥75 years. Results: The total sample of 4864 patients had a mean age of 56.4 â€‹± â€‹14.4 years. The mean change in pre-to postoperative KPS was -1.43. For each 1-year increase in patient age, the adjusted change in postoperative KPS was -0.11 (95% CI -0.14 - - 0.07). In multivariable analysis, patients ≥75 years had an odds ratio of 1.51 to experience postoperative functional decline (95%CI 1.21-1.88) and an odds ratio of 2.04 to die (95%CI 1.33-3.13), compared to younger patients. Discussion: Patients with intracranial tumors treated surgically showed a minor decline in their postoperative functional status. Age was associated with this decline in function, but only to a small extent. Conclusion: Patients ≥75 years were more likely to experience a clinically meaningful decline in function and about two times as likely to die within the first 6 months after surgery, compared to younger patients.

Development of a Complication- and Treatment-Aware Prediction Model for Favorable Functional Outcome in Aneurysmal Subarachnoid Hemorrhage Based on Machine Learning.

BACKGROUND: Current prognostic tools in aneurysmal subarachnoid hemorrhage (aSAH) are constrained by being primarily based on patient and disease characteristics on admission. OBJECTIVE: To develop and validate a complication- and treatment-aware outcome prediction tool in aSAH. METHODS: This cohort study included data from an ongoing prospective nationwide multicenter registry on all aSAH patients in Switzerland (Swiss SOS [Swiss Study on aSAH]; 2009-2015). We trained supervised machine learning algorithms to predict a binary outcome at discharge (modified Rankin scale [mRS] ≤ 3: favorable; mRS 4-6: unfavorable). Clinical and radiological variables on admission ("Early" Model) as well as additional variables regarding secondary complications and disease management ("Late" Model) were used. Performance of both models was assessed by classification performance metrics on an out-of-sample test dataset. RESULTS: Favorable functional outcome at discharge was observed in 1156 (62.0%) of 1866 patients. Both models scored a high accuracy of 75% to 76% on the test set. The "Late" outcome model outperformed the "Early" model with an area under the receiver operator characteristics curve (AUC) of 0.85 vs 0.79, corresponding to a specificity of 0.81 vs 0.70 and a sensitivity of 0.71 vs 0.79, respectively. CONCLUSION: Both machine learning models show good discrimination and calibration confirmed on application to an internal test dataset of patients with a wide range of disease severity treated in different institutions within a nationwide registry. Our study indicates that the inclusion of variables reflecting the clinical course of the patient may lead to outcome predictions with superior predictive power compared to a model based on admission data only.

Evaluation of the 6-minute walking test as a smartphone app-based self-measurement of objective functional impairment in patients with lumbar degenerative disc disease.

OBJECTIVE: Digital transformation enables new possibilities to assess objective functional impairment (OFI) in patients with lumbar degenerative disc disease (DDD). This study examines the psychometric properties of an app-based 6-minute walking test (6WT) and determines OFI in patients with lumbar DDD. METHODS: The maximum 6-minute walking distance (6WD) was determined in patients with lumbar DDD. The results were expressed as raw 6WDs (in meters), as well as in standardized z-scores referenced to age- and sex-specific values of spine-healthy volunteers. The 6WT results were assessed for reliability and content validity using established disease-specific patient-reported outcome measures. RESULTS: Seventy consecutive patients and 330 volunteers were enrolled. The mean 6WD was 370 m (SD 137 m) in patients with lumbar DDD. Significant correlations between 6WD and the Core Outcome Measures Index for the back (r = -0.31), Zurich Claudication Questionnaire (ZCQ) symptom severity (r = -0.32), ZCQ physical function (r = -0.33), visual analog scale (VAS) for back pain (r = -0.42), and VAS for leg pain (r = -0.32) were observed (all p < 0.05). The 6WT revealed good test-retest reliability (intraclass correlation coefficient 0.82), and the standard error of measurement was 58.3 m. A 4-tier severity stratification classified patients with z-scores > -1 (no OFI), -1 to -1.9 (mild OFI), -2 to -2.9 (moderate OFI), and ≤ -3 (severe OFI). CONCLUSIONS: The smartphone app-based self-measurement of the 6WT is a convenient, reliable, and valid way to determine OFI in patients with lumbar DDD. The 6WT app facilitates the digital evaluation and monitoring of patients with lumbar DDD.