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Primary spinal cord astrocytomas are rare, hence few data exist about the prognostic significance of molecular markers. Here we analyze a panel of molecular alterations in association with the clinical course. Histology and genome sequencing was performed in 26 spinal astrocytomas operated upon between 2000 and 2020. Next-generation DNA/RNA sequencing (NGS) and methylome analysis were performed to determine molecular alterations. Histology and NGS allowed the distinction of 5 tumor subgroups: glioblastoma IDH wildtype (GBM); diffuse midline glioma H3 K27M mutated (DMG-H3); high-grade astrocytoma with piloid features (HAP); diffuse astrocytoma IDH mutated (DA), diffuse leptomeningeal glioneural tumors (DGLN) and pilocytic astrocytoma (PA). Within all tumor entities GBM (median OS: 5.5 months), DMG-H3 (median OS: 13 months) and HAP (median OS: 8 months) showed a fatal prognosis. DMG-H3 tend to emerge in adolescence whereas GBM and HAP develop in the elderly. HAP are characterized by CDKN2A/B deletion and ATRX mutation. 50% of PA tumors carried a mutation in the PIK3CA gene which is seemingly associated with better outcome (median OS: PIK3CA mutated 107.5 vs 45.5 months in wildtype PA). This exploratory molecular profiling of spinal cord astrocytomas allows to identify distinct subgroups by combining molecular markers and histomorphology. DMG-H3 tend to develop in adolescence with a similar dismal prognosis like GBM and HAP in the elderly. We here describe spinal HAP with a distinct molecular profile for the first time.

The application of transcranial direct current stimulation (tDCS) at home for the treatment of major depressive disorder (MDD) is the subject of current clinical trials. This is due to its positive safety profile, cost-effectiveness, and potential scalability for a wide outreach in clinical practice. Here, we provide a systematic review of the available studies and also a report on the results of a randomized controlled trial (RCT) on tDCS at home for the treatment of MDD. This trial had to be prematurely terminated due to safety concerns. The HomeDC trial is a double-blinded, placebo-controlled, parallel-group study. Patients with MDD (DSM-5) were randomized to active or sham tDCS. Patients conducted tDCS at home for 6 weeks with 5 sessions/week (30 min at 2 mA) anode over F3, cathode over F4. Sham tDCS resembled active tDCS, with ramp-in and ramp-out periods, but without intermittent stimulation. The study was prematurely terminated due to an accumulation of adverse events (AEs, skin lesions), so that only 11 patients were included. Feasibility was good. Safety monitoring was not sufficient enough to detect or prevent AEs within an appropriate timeframe. Regarding antidepressant effects, the reduction in depression scales over time was significant. However, active tDCS was not superior to sham tDCS in this regard. Both the conclusions from this review and the HomeDC trial show that there are several critical issues with the use of tDCS at home that need to be addressed. Nevertheless the array of transcranial electric simulation (TES) methods that this mode of application offers, including tDCS, is highly interesting and warrants further investigation in high quality RCTs. Trial registration: www.clinicaltrials.gov. Trial registration number: NCT05172505. Registration date: 12/13/2021, https://clinicaltrials.gov/ct2/show/NCT05172505. Graphical abstract *Consider, if feasible to do so, reporting the number of records identified from each database or register searched (rather than the total number across all databases/registers) **If automation tools were used, indicate how many records were excluded by a human and how many were excluded by automation tools From: Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:n71. https://doi.org/10.1136/bmj.n71. For more information, visit: http://www.prisma-statement.org/

Background: The number of total ankle arthroplasty (TAA) procedures increased rapidly in the last years and so have its complications. The main pillars in treating failed TAA are revision total ankle arthroplasty (RTAA), revision total ankle arthrodesis (RAA), or revision tibiotalocalcaneal fusion (RTTC). To evaluate these options, we compared clinical, radiologic, and patient-reported outcomes. Methods: A single-center, retrospective review of 111 cases of revision procedures of failed TAA from 2006 to 2020 was performed. Patients undergoing polyethylene exchange and revision of one metallic component were excluded. Demographic data, failure, and survival rates were analyzed. The European Foot and Ankle Society (EFAS) score and radiographic changes in the subtalar joint were evaluated. The average follow-up was 67.89 ± 40.51 months. Results: One hundred eleven patients underwent removal of TAA. The procedures included 40 revisions of both metallic components, 46 revision total ankle arthrodesis and 25 revision tibiotalocalcaneal fusion. The overall failure rate in the cohort was 5.41% (6/111). The failure rate after RAA was 4.35 times higher than that of RTAA, whereas RTTC did not show failures. RTAA and RTTC lead to a 1-year and 5-year survival rate of 100%. RAA resulted in a 1-year survival rate of 90% and a 5-year survival rate of 85%. The mean EFAS score in the cohort was 12.02 ± 5.83. Analysis of the EFAS score showed that RTTC provided the most reliable pain reduction, and RTAA achieved the best gait pattern. RAA resulted in poorer clinical results. Subtalar joint degeneration occurred significantly less in the RTAA group ( P = .01). Conclusion: This retrospective study suggests lower failure rates, increased short-term survival and a better clinical outcomes of revision arthroplasty and tibiotalocalcaneal fusion than ankle arthrodesis. Revision arthroplasty is a promising solution in treating failed total ankle arthroplasty considering lower rate of subsequent adjacent joint degeneration. Level of Evidence: Level III, non-randomized observational study.

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