Association of Medical Comorbidities With Objective Functional Impairment in Lumbar Degenerative Disc Disease

STUDY DESIGN Analysis of a prospective 2-center database. OBJECTIVES Medical comorbidities co-determine clinical outcome. Objective functional impairment (OFI) provides a supplementary dimension of patient assessment. We set out to study whether comorbidities are associated with the presence and degree of OFI in this patient population. METHODS Patients with degenerative diseases of the spine preoperatively performed the timed-up-and-go (TUG) test and a battery of questionnaires. Comorbidities were quantified using the Charlson Comorbidity Index (CCI) and the American Society of Anesthesiology (ASA) grading. Crude and adjusted linear regression models were fitted. RESULTS Of 375 included patients, 97 (25.9%) presented at least some degree of medical comorbidity according to the CCI, and 312 (83.2%) according to ASA grading. In the univariate analysis, the CCI was inconsistently associated with OFI. Only patients with low-grade CCI comorbidity displayed significantly higher TUG test times (p = 0.004). In the multivariable analysis, this effect persisted for patients with CCI = 1 (p = 0.030). Regarding ASA grade, patients with ASA = 3 exhibited significantly increased TUG test times (p = 0.003) and t-scores (p = 0.015). This effect disappeared after multivariable adjustment (p = 0.786 and p = 0.969). In addition, subjective functional impairment according to ODI, and EQ5D index was moderately associated with comorbidities according to ASA (all p < 0.05). CONCLUSION The degree of medical comorbidities appears only weakly and inconsistently associated with OFI in patients scheduled for degenerative lumbar spine surgery, especially after controlling for potential confounders. TUG testing may be valid even in patients with relatively severe comorbidities who are able to complete the test

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

Non-assisted versus neuro-navigated and XperCT-guided external ventricular catheter placement: a comparative cadaver study

Background and purpose: Accurate placement of an external ventricular drain (EVD) for the treatment of hydrocephalus is of paramount importance for its functionality and in order to minimize morbidity and complications. The aim of this study was to compare two different drain insertion assistance tools with the traditional free-hand anatomical landmark method, and to measure efficacy, safety and precision. Methods: Ten cadaver heads were prepared by opening large bone windows centered on Kocher's points on both sides. Nineteen physicians, divided in two groups (trainees and board certified neurosurgeons) performed EVD insertions. The target for the ventricular drain tip was the ipsilateral foramen of Monro. Each participant inserted the external ventricular catheter in three different ways: 1) free-hand by anatomical landmarks, 2) neuronavigation-assisted (NN), and 3) XperCT-guided (XCT). The number of ventricular hits and dangerous trajectories; time to proceed; radiation exposure of patients and physicians; distance of the catheter tip to target and size of deviations projected in the orthogonal plans were measured and compared. Results: Insertion using XCT increased the probability of ventricular puncture from 69.2 to 90.2% (p = 0.02). Non-assisted placements were significantly less precise (catheter tip to target distance 14.3 ± 7.4mm versus 9.6 ± 7.2mm, p = 0.0003). The insertion time to proceed increased from 3.04 ± 2.06min. to 7.3 ± 3.6min. (p < 0.001). The X-ray exposure for XCT was 32.23mSv, but could be reduced to 13.9mSv if patients were initially imaged in the hybrid-operating suite. No supplementary radiation exposure is needed for NN if patients are imaged according to a navigation protocol initially. Conclusion: This ex vivo study demonstrates a significantly improved accuracy and safety using either NN or XCT-assisted methods. Therefore, efforts should be undertaken to implement these new technologies into daily clinical practice. However, the accuracy versus urgency of an EVD placement has to be balanced, as the image-guided insertion technique will implicate a longer preparation time due to a specific image acquisition and trajectory planning

Mechanistic insight into RET kinase inhibitors targeting the DFG-out conformation in RET-rearranged cancer

Oncogenic fusion events have been identified in a broad range of tumors. Among them, RET rearrangements represent distinct and potentially druggable targets that are recurrently found in lung adenocarcinomas. Here, we provide further evidence that current anti-RET drugs may not be potent enough to induce durable responses in such tumors. We report that potent inhibitors such as AD80 or ponatinib that stably bind in the DFG-out conformation of RET may overcome these limitations and selectively kill RET-rearranged tumors. Using chemical genomics in conjunction with phosphoproteomic analyses in RET-rearranged cells we identify the CCDC6-RETI788N mutation and drug-induced MAPK pathway reactivation as possible mechanisms, by which tumors may escape the activity of RET inhibitors. Our data provide mechanistic insight into the druggability of RET kinase fusions that may be of help for the development of effective therapies targeting such tumors

Assessment of the minimum clinically important difference in the timed up and go test after surgery for lumbar degenerative disc disease

BACKGROUND The Timed Up and Go Test (TUG Test) has previously been described as a reliable tool to evaluate objective functional impairment in patients with degenerative disc disease. OBJECTIVE The aim of this study was to assess the minimum clinically important difference (MCID) of the TUG Test. METHODS The TUG Test (measured in seconds) was correlated with validated patient-reported outcome measures (PROs) of pain intensity (Visual Analog Scale for back and leg pain), functional impairment (Oswestry Disability Index, Roland Morris Disability Index), and health-related quality of life measures (Short Form-12 and EuroQol 5D). Three established methods were used to establish anchor-based MCID values using responders of the following PROs (Visual Analog Scale back and leg pain, Oswestry Disability Index, Roland Morris Disability Index, EuroQol 5D index, and Short Form-12 Physical Component Summary) as anchors: (1) average change, (2) minimum detectable change, and (3) change difference approach. RESULTS One hundred patients with a mean ± SD age of 56.2 ± 16.1 years, 57 (57%) male, 45 patients undergoing microdiscectomy, 35 undergoing lumbar decompression, and 20 undergoing fusion surgery were studied. The 3 MCID computation methods revealed a range of MCID values according to the PRO used from 0.9 s (Oswestry Disability Index based on the change difference approach) to 6.0 s (EuroQol 5D index based on the minimum detectable change approach), with a mean MCID of 3.4 s for all measured PROs. CONCLUSION The MCID for the TUG Test time is highly variable depending on the computation technique used. The average TUG Test MCID was 3.4 s using all 3 methods and all anchors. ABBREVIATIONS D3, day 3DDD, degenerative disc diseaseEQ5D, EuroQol 5DFU, follow-upHRQoL, health-related quality of lifeMCID, minimum clinically important differenceODI, Oswestry Disability IndexOFI, objective functional impairmentPCS, Physical Component SummaryPRO, patient-reported outcome measureRMDI, Roland-Morris Disability IndexSF-12, Short Form 12TUG Test, Time Up and Go TestVAS, Visual Analog Scale

Beurteilung funktioneller Einschränkungen bei degenerativen Erkrankungen der Lendenwirbelsäule: Wer hat Recht – der Arzt, der Patient oder der objektive Test?

Zusammenfassung. Zur exakten Erfassung von Schmerzen, funktionellen Einschränkungen und gesundheitsbezogener Lebensqualität bei Patienten mit degenerativen Wirbelsäulenerkrankungen existiert eine Reihe validierter Messinstrumente. Neben der Beurteilung durch den Therapeuten sowie «subjektiven» patientenorientierten Messmethoden (PROMs) wurde in den vergangenen Jahren der «Timed Up and Go»(TUG)-Test systematisch untersucht und als krankheitsspezifisches Messinstrument validiert. Heute kann eine objektive funktionelle Einschränkung (OFI = Objective Functional Impairment) in wenigen Sekunden und kostenfrei mithilfe einer Smartphone-Applikation bestimmt werden. Die Bestimmung von Z- oder T-Werten, die TUG-Testergebnisse in Relation zur Populationsnorm setzen, ermöglichen eine alters- und geschlechtsadjustierte Ergebnisinterpretation. Diese Übersichtsarbeit fasst die aktuellen Erkenntnisse zu objektiven Messmethoden bei degenerativen Wirbelsäulenpathologien inklusive deren Vor- und Nachteile zusammen und vergleicht sie mit den bisherigen Beurteilungsmethoden für funktionelle Outcomes. </jats:p