Citations

Background Accurate and timely prehospital detection of large vessel occlusion (LVO) is critical for optimizing patient triage and initiating appropriate reperfusion therapies. Recent advances in portable stroke detection technologies, such as electroencephalography (EEG) and transcranial Doppler (TCD) ultrasound, offer potential solutions but their diagnostic performance remains unclear. Methods We searched PubMed, Scopus, Embase, and Web of Science, following the PRISMA guidelines. Studies were included if they assessed the diagnostic performance of non-invasive prehospital LVO detection tools compared to CT or MR angiography. Risk of bias was assessed using the QUADAS-2 tool. Results A total of 13 studies were included, examining various portable detection tools including EEG or neurophysiological monitoring, ultrasound-based techniques including TCD or TCCD, portable Openwater optical blood flow monitor and cranial accelerometry. The pooled diagnostic odds ratio (DOR) was 52.7 (95% CI: 28.3–97.8), indicating strong diagnostic performance, with significant heterogeneity among studies (I 2 = 67.3%, P < 0.001). Subgroup analysis revealed that TCD-based methods had the highest DOR (120.4, 95% CI: 76.9–188.7), followed by other tools (26.8, 95% CI: 13.7–52.6), and EEG (18.2, 95% CI: 9.1–36.3). The pooled sensitivity was 87.4% (95% CI: 82.5–91.0) and specificity was 89.39% (95% CI: 83.0–93.5) across all methods. TCD-based methods showed the highest specificity (95.0%, 95% CI: 91.8–97.0). Conclusion Non-invasive prehospital LVO detection tools show promising diagnostic performance, particularly TCD-based methods. Future studies should focus on validating these tools in larger, diverse populations to enhance prehospital stroke triage and improve patient outcomes.

Nuclear clearance and cytoplasmic aggregation of TAR DNA-binding protein 43 (TDP-43) are observed in many neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although TDP-43 dysregulation of splicing has emerged as a key event in these diseases, TDP-43 can also regulate polyadenylation; yet this has not been adequately studied. Here, we applied the dynamic analysis of polyadenylation from an RNA-Seq (DaPars) tool to ALS/FTD transcriptome datasets and report extensive alternative polyadenylation (APA) upon TDP-43 alteration in ALS/FTD cell models and postmortem ALS/FTD neuronal nuclei. Importantly, many identified APA genes highlight pathways implicated in ALS/FTD pathogenesis. To determine the functional relevance of APA elicited by TDP-43 nuclear depletion, we examined microtubule affinity regulating kinase 3 (MARK3). Nuclear loss of TDP-43 yielded increased expression of MARK3 transcripts with longer 3′ UTRs, corresponding with a change in the subcellular distribution of MARK3 and increased neuronal tau S262 phosphorylation. Our findings define changes in polyadenylation site selection as a previously understudied feature of TDP-43–driven disease pathology in ALS/FTD and highlight a potentially important mechanistic link between TDP-43 dysfunction and tau regulation.

OBJECTIVE The purpose of this study was to evaluate the risks and benefits of removing painful pelvic/iliac screws in spine fusion surgery patients. METHODS A retrospective review identified patients who had traditional iliac and S2-alar-iliac (S2AI) screws removed for pain. The minimum follow-up was 24 months. RESULTS Fifty-two patients (75% women) were included with a mean age of 63 years, BMI of 28, and follow-up of 65 months. Most of the removed screws were S2AI (83%) compared with traditional iliac screws (17%). Forty-three patients (83%) had improvement in their pelvic screw related–pain following removal. Eight patients (15%) experienced lumbosacral mechanical complications following pelvic screw removal including sacral fracture (n = 3, 6%) and/or L4–5 or L5–S1 rod fracture (n = 7, 13%). On multivariable analysis, risk factors for mechanical complications following pelvic screw removal included a longer fusion construct (OR 1.34, p = 0.035), greater postoperative L4–S1 lordosis (OR 1.14, p = 0.04, ideal cutoff > 40°), and lack of bone morphogenetic protein (BMP; OR 0.03, p = 0.02). Ten patients (19%) underwent subsequent SI joint fusion following pelvic screw removal, and higher standing pelvic incidence (OR 1.10, p = 0.03) was the only independent predictor of SI fusion. CONCLUSIONS Removal of painful pelvic screws resulted in a high rate of postoperative pain relief, albeit with a risk of lumbosacral mechanical complications and subsequent SI joint fusion. Patients at risk for lumbosacral mechanical complications following pelvic screw removal included those with longer fusion constructs, more lordosis from L4 to S1 (> 40°), and lack of BMP. Patients at risk for receiving an instrumented SI joint fusion following pelvic screw removal included those with a higher pelvic incidence.

OBJECTIVE While traditional literature in adult spinal deformity (ASD) examining mechanical complications has focused on proximal junctional kyphosis and failure, distal junctional failure (DJF) of constructs ending at the sacrum with or without spinopelvic fixation remains less explored. The current study sought to 1) propose a new DJF classification with a panel of experienced deformity surgeons, and 2) analyze intra- and interreliability of the novel classification. METHODS A prior review study was completed that identified all types of distal complications for lumbosacral fusions. A panel of 25 experienced spinal deformity surgeons used a modified Delphi approach with three rounds of review to create a classification system. Ten deformity surgeons then reviewed a representative series of 14 de-identified cases to assess the interrater reliability of the classification system using the intraclass correlation coefficient (ICC). A second round of review was conducted by each investigator to determine intrarater reliability using Cohen’s kappa coefficient. RESULTS Complications were classified as acute (< 90 days from the date of surgery) or chronic (≥ 3 months from the date of surgery). Acute failures included mechanical failure of the screws or screw-rod interface, such as pelvic set plug dissociation, tulip head dissociation, and fracture of the pelvic screw at any point along its trajectory. Fractures of the rod (proximal vs distal to S1) and distal bony anatomy (sacrum vs pelvis) were included, as was failure of the offset connector. Chronic failures also consisted of pseudarthrosis at distal levels, sacroiliac joint (SIJ) pain, screw halo formation, and painful screw prominence. The intrarater and interrater reliability were both high with Cohen’s kappa of 0.91 and an ICC of 0.98, respectively. CONCLUSIONS These data provide a comprehensive and systematic classification scheme of distal complications following long-segment ASD fusion to the sacrum. This new paradigm will allow for more detailed and consistent reporting of distal junctional complications following spinopelvic fusion, with or without supplemental pelvic fixation and/or concomitant SIJ fusion. This classification scheme resulted in high intra- and interrater reliability.

Abstract Multiple myeloma (MM) is an incurable malignancy of clonally expanded plasma cells shaped by complex interactions with the immune microenvironment. To investigate immune factors driving treatment response and resistance, we conducted multi-omics profiling including CD138 neg single-cell RNA sequencing of 243 bone marrow samples from 102 patients (631,226 cells) and CD138 pos bulk RNA and whole-genome sequencing from 209 samples. Longitudinal analyses revealed that interferon gamma signaling impairs T cell memory after autologous stem cell transplant, while naïve B cell abundance and immunoglobulin diversity correlated with improved progression-free survival (HR = 0.48, p = 2.3e -4 ). At disease progression, MM cells upregulated cancer-testis antigens and immune effector genes, with concurrent B cell depletion, enrichment of myeloid-derived suppressor cell genes in monocytes, and T cell exhaustion. These findings highlight dynamic immune-tumor interactions, identifying naïve B cell reconstitution as a biomarker of durable response, and cancer-testis antigens as potential targets for high-risk disease at progression. Statement of Significance Longitudinal profiling of multiple myeloma and the immune microenvironment revealed dynamic immune-tumor interactions across the disease course. Dysfunctional CD8⁺ T cells limited memory formation post-transplant, while naïve B recovery associated with sustained treatment response. At progression, cancer-testis antigen expression associated with immunosuppression, revealing novel mechanisms of immune escape.