Multicenter external validation of prediction models for clinical outcomes after spinal fusion for lumbar degenerative disease.

BACKGROUND: Clinical prediction models (CPM), such as the SCOAP-CERTAIN tool, can be utilized to enhance decision-making for lumbar spinal fusion surgery by providing quantitative estimates of outcomes, aiding surgeons in assessing potential benefits and risks for each individual patient. External validation is crucial in CPM to assess generalizability beyond the initial dataset. This ensures performance in diverse populations, reliability and real-world applicability of the results. Therefore, we externally validated the tool for predictability of improvement in oswestry disability index (ODI), back and leg pain (BP, LP). METHODS: Prospective and retrospective data from multicenter registry was obtained. As outcome measure minimum clinically important change was chosen for ODI with ≥ 15-point and ≥ 2-point reduction for numeric rating scales (NRS) for BP and LP 12 months after lumbar fusion for degenerative disease. We externally validate this tool by calculating discrimination and calibration metrics such as intercept, slope, Brier Score, expected/observed ratio, Hosmer-Lemeshow (HL), AUC, sensitivity and specificity. RESULTS: We included 1115 patients, average age 60.8 ± 12.5 years. For 12-month ODI, area-under-the-curve (AUC) was 0.70, the calibration intercept and slope were 1.01 and 0.84, respectively. For NRS BP, AUC was 0.72, with calibration intercept of 0.97 and slope of 0.87. For NRS LP, AUC was 0.70, with calibration intercept of 0.04 and slope of 0.72. Sensitivity ranged from 0.63 to 0.96, while specificity ranged from 0.15 to 0.68. Lack of fit was found for all three models based on HL testing. CONCLUSIONS: Utilizing data from a multinational registry, we externally validate the SCOAP-CERTAIN prediction tool. The model demonstrated fair discrimination and calibration of predicted probabilities, necessitating caution in applying it in clinical practice. We suggest that future CPMs focus on predicting longer-term prognosis for this patient population, emphasizing the significance of robust calibration and thorough reporting.

Ceramide accumulation induces mitophagy and impairs ß-oxidation in PINK1 deficiency.

Energy production via the mitochondrial electron transport chain (ETC) and mitophagy are two important processes affected in Parkinson's disease (PD). Interestingly, PINK1, mutations of which cause early-onset PD, plays a key role in both processes, suggesting that these two mechanisms are connected. However, the converging link of both pathways currently remains enigmatic. Recent findings demonstrated that lipid aggregation, along with defective mitochondria, is present in postmortem brains of PD patients. In addition, an increasing body of evidence shows that sphingolipids, including ceramide, are altered in PD, supporting the importance of lipids in the pathophysiology of PD. Here, we identified ceramide to play a crucial role in PINK1-related PD that was previously linked almost exclusively to mitochondrial dysfunction. We found ceramide to accumulate in mitochondria and to negatively affect mitochondrial function, most notably the ETC. Lowering ceramide levels improved mitochondrial phenotypes in pink1-mutant flies and PINK1-deficient patient-derived fibroblasts, showing that the effects of ceramide are evolutionarily conserved. In addition, ceramide accumulation provoked ceramide-induced mitophagy upon PINK1 deficiency. As a result of the ceramide accumulation, ß-oxidation in PINK1 mutants was decreased, which was rescued by lowering ceramide levels. Furthermore, stimulation of ß-oxidation was sufficient to rescue PINK1-deficient phenotypes. In conclusion, we discovered a cellular mechanism resulting from PD-causing loss of PINK1 and found a protective role of ß-oxidation in ETC dysfunction, thus linking lipids and mitochondria in the pathophysiology of PINK1-related PD. Furthermore, our data nominate ß-oxidation and ceramide as therapeutic targets for PD.

Sex Differences in Patient-rated Outcomes After Lumbar Spinal Fusion for Degenerative Disease: A Multicenter Cohort Study.

STUDY DESIGN: Heterogeneous data collection via a mix of prospective, retrospective, and ambispective methods. OBJECTIVE: To evaluate the effect of biological sex on patient-reported outcomes after spinal fusion surgery for lumbar degenerative disease. SUMMARY OF BACKGROUND DATA: Current literature suggests sex differences regarding clinical outcome after spine surgery may exist. Substantial methodological heterogeneity and limited comparability of studies warrants further investigation of sex-related differences in treatment outcomes. METHODS: We analyzed patients who underwent spinal fusion with or without pedicle screw insertion for lumbar degenerative disease included within a multinational study, comprising patients from 11 centers in 7 countries. Absolute values and change scores (change from pe-operative baseline to post-operative follow-up) for 12-month functional impairment (Oswestry disability index [ODI]) and back and leg pain severity (numeric rating scale [NRS]) were compared between male and female patients. Minimum clinically important difference (MCID) was defined as > 30% improvement. RESULTS: Six-hundred-sixty (59%) of 1115 included patients were female. Female patients presented with significantly baseline ODI (51.5 ± 17.2 vs. 47.8 ± 17.9, P<0.001) and back pain (6.96 ± 2.32 vs. 6.60 ± 2.30, P=0.010) and leg pain (6.49 ± 2.76 vs. 6.01 ± 2.76, P=0.005). At 12-months, female patients still reported significantly higher ODI (22.76 ± 16.97 vs. 20.50 ± 16.10, P=0.025), but not higher back (3.13 ± 2.38 vs. 3.00 ± 2.40, P=0.355) or leg pain (2.62 ± 2.55 vs. .34 ± 2.43, P=0.060). Change scores at 12 months did not differ significantly among male and female patients in ODI (∆ 1.31, 95% CI -3.88-1.25, P=0.315), back (∆ 0.22, 95% CI -0.57-0.12, P=0.197) and leg pain (∆ 0.16, 95% CI -0.56-0.24, P=0.439). MCID at 12-months was achieved in 330 (77.5%) male patients and 481 (76.3%) female patients (P=0.729) for ODI. CONCLUSION: Both sexes experienced a similar benefit from surgery in terms of relative improvement in scores for functional impairment and pain. Although female patients reported a higher degree of functional impairment and pain preoperatively, at 12 months only their average scores for functional impairment remained higher than those for their male counterparts, while absolute pain scores were similar for female and male patients.

Challenges in Coagulation Management in Neurosurgical Diseases: A Scoping Review, Development, and Implementation of Coagulation Management Strategies.

Bleeding and thromboembolic (TE) complications in neurosurgical diseases have a detrimental impact on clinical outcomes. The aim of this study is to provide a scoping review of the available literature and address challenges and knowledge gaps in the management of coagulation disorders in neurosurgical diseases. Additionally, we introduce a novel research project that seeks to reduce coagulation disorder-associated complications in neurosurgical patients. The risk of bleeding after elective craniotomy is about 3%, and higher (14-33%) in other indications, such as trauma and intracranial hemorrhage. In spinal surgery, the incidence of postoperative clinically relevant bleeding is approximately 0.5-1.4%. The risk for TE complications in intracranial pathologies ranges from 3 to 20%, whereas in spinal surgery it is around 7%. These findings highlight a relevant problem in neurosurgical diseases and current guidelines do not adequately address individual circumstances. The multidisciplinary COagulation MAnagement in Neurosurgical Diseases (COMAND) project has been developed to tackle this challenge by devising an individualized coagulation management strategy for patients with neurosurgical diseases. Importantly, this project is designed to ensure that these management strategies can be readily implemented into healthcare practices of different types and with sustainable integration.