Over the past two decades, advances in computational power and data availability combined with increased accessibility to pre-trained models have led to an exponential rise in machine learning (ML) publications. While ML may have the potential to transform healthcare, this sharp increase in ML research output without focus on methodological rigor and standard reporting guidelines has fueled a reproducibility crisis. In addition, the rapidly growing complexity of these models compromises their interpretability, which currently impedes their successful and widespread clinical adoption. In medicine, where failure of such models may have severe implications for patients’ health, the high requirements for accuracy, robustness, and interpretability confront ML researchers with a unique set of challenges. In this review, we discuss the semantics of reproducibility and interpretability, as well as related issues and challenges, and outline possible solutions to counteracting the “black box”. To foster reproducibility, standard reporting guidelines need to be further developed and data or code sharing encouraged. Editors and reviewers may equally play a critical role by establishing high methodological standards and thus preventing the dissemination of low-quality ML publications. To foster interpretable learning, the use of simpler models more suitable for medical data can inform the clinician how results are generated based on input data. Model-agnostic explanation tools, sensitivity analysis, and hidden layer representations constitute further promising approaches to increase interpretability. Balancing model performance and interpretability are important to ensure clinical applicability. We have now reached a critical moment for ML in medicine, where addressing these issues and implementing appropriate solutions will be vital for the future evolution of the field.

Study Design.: Heterogeneous data collection through 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. Materials and 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 seven countries. Absolute values and change scores (change from preoperative baseline to postoperative 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), 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. 2.34±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 to 1.25, P=0.315), back (∆0.22, 95% CI: -0.57 to 0.12, P=0.197), and leg pain (∆0.16, 95% CI: -0.56 to 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.

Developmental gene expression data from medulloblastoma (MB) suggest that WNT-MB originates from the region of the embryonic lower rhombic lip (LRL), whereas SHH-MB and non-WNT/non-SHH MB arise from cerebellar precursor matrix regions. This study aimed to analyze detailed intraoperative data with regard to the site of origin (STO) and compare these findings with the hypothesized regions of origin associated with the molecular group. A review of the institutional database identified 58 out of 72 pediatric patients who were operated for an MB at our department between 1996 and 2020 that had a detailed operative report and a surgical video as well as clinical and genetic classification data available for analysis. The STO was assessed based on intraoperative findings. Using the intraoperatively defined STO, “correct” prediction of molecular groups was feasible in 20% of WNT-MB, 60% of SHH-MB and 71% of non-WNT/non-SHH MB. The positive predictive values of the neurosurgical inspection to detect the molecular group were 0.21 (95% CI 0.08–0.48) for WNT-MB, 0.86 (95% CI 0.49–0.97) for SHH-MB and 0.73 (95% CI 0.57–0.85) for non-WNT/non-SHH MB. The present study demonstrated a limited predictive value of the intraoperatively observed STO for the prediction of the molecular group of MB.

The objective is to provide a treatment algorithm for pediatric patients with intracranial cavernous malformations (CMs) based on our experience. Patients < 18 years of age who were treated either surgically or conservatively at the authors’ institution between 1982 and 2019 were retrospectively evaluated. A total of 61 pediatric patients were treated at the authors’ institution: 39 with lobar CMs; 18 with deep CMs, including 12 in the brainstem and 6 in the basal ganglia; and 4 with CMs in the cerebellar hemispheres. Forty-two patients underwent surgery, and 19 were treated conservatively. The median follow-up time was 65 months (1–356 months). In surgically treated patients, lesions were larger (2.4 cm vs 0.9 cm, p < 0.001). In patients with lobar CMs, seizures were more common (72% vs 21%, p = 0.003) in the surgery group than in conservatively managed patients. In deep CMs, modified Rankin scale (mRS) was higher (4 vs 1, p = 0.003) in the surgery group than in conservatively treated patients. At the time of last follow-up, no differences in Wieser outcome class I were seen (86% vs 67%) in lobar CMs, and mRS scores had aligned between the treatment groups in deep CMs (1 vs 0). We encountered no new permanent neurological deficit at time of last follow-up. We propose a treatment algorithm according to lesion location and size, burden of symptoms, epilepsy workup, and further clinical course during observation. A conservative management is safe in pediatric patients with asymptomatic CMs. Gross total resection should be the aim in patients with symptomatic lobar CMs. A less aggressive approach with subtotal resection, when required to prevent neurological compromise, sustainably improves neurological outcome in patients with deep CMs.