Citations

OBJECTIVE Deficiency in patient education has been correlated with increased disease-related morbidity and decreased access to care. However, the associations between educational level, preoperative disease severity, and postoperative outcomes in patients with lumbar spondylolisthesis have yet to be explored. METHODS The spondylolisthesis dataset of the Quality Outcomes Database (QOD)—a cohort with prospectively collected data by the SpineCORe study team of the 12 highest enrolling sites with an 81% follow-up at 5 years —was utilized and stratified for educational level. Patients were classified into three categories (high school or less, graduate, or postgraduate). Patient-reported outcome measures (PROMs) documented at baseline and follow-up included Oswestry Disability Index (ODI) score, EQ-5D in quality-adjusted life years, and numeric rating scale (NRS) scores for back and leg pain. Disease severity was measured with PROMs. Postoperatively, patients also completed the North American Spine Society assessment to measure their satisfaction with surgery. Multivariable regression analysis was used to compare education level with disease severity and postoperative outcomes. RESULTS A total of 608 patients underwent analysis, with 260 individuals (42.8%) at an educational level of high school or less. On univariate analysis, baseline disease severity was worse among patients with lower levels of education. On multivariable regression analysis, patients with postgraduate level of education had significantly lower ODI scores (β = −3.75, 95% CI −7.31 to −0.2, p = 0.039) compared to graduates, while the other PROMs were not associated with significant differences at baseline. Five years postoperatively, patients from various educational backgrounds exhibited similar rates of minimal clinically important differences in PROMs. Nevertheless, patients with the lowest educational level had higher ODI scores (27.1, p < 0.01), lower EQ-5D scores (0.701, p < 0.01), and higher NRS leg pain (3.0, p < 0.01) and back pain (4.0, p < 0.01) scores compared to those with graduate or postgraduate levels of education. The odds for postoperative satisfaction were also comparable between cohorts at 5 years (reference, graduate level; high school or less, OR 0.87, 95% CI 0.46–1.64, p = 0.659; postgraduate, OR 1.6, 95% CI 0.7–3.65, p = 0.262). CONCLUSIONS Lower patient education level was associated with a greater baseline disease severity in patients with lumbar spondylolisthesis. Surgery demonstrated similar benefits irrespective of educational background; however, individuals with lower educational level reported lower outcomes overall. This emphasizes the need for enhanced health literacy to mitigate disparities for reported outcomes.

Cells expressing features of senescence, including upregulation of p21 and p16, appear transiently following tissue injury, yet the properties of these cells or how they contrast with age-induced senescent cells remains unclear. Here, we used skeletal injury as a model and identified the rapid appearance following fracture of p21 + cells expressing senescence markers, mainly as osteochondroprogenitors (OCHs) and neutrophils. Targeted genetic clearance of p21 + cells suppressed senescence-associated signatures within the fracture callus and accelerated fracture healing. By contrast, p21 + cell clearance did not alter bone loss due to aging; conversely, p16 + cell clearance, known to alleviate skeletal aging, did not affect fracture healing. Following fracture, p21 + neutrophils were enriched in signaling pathways known to induce paracrine stromal senescence, while p21 + OCHs were highly enriched in senescence-associated secretory phenotype factors known to impair bone formation. Further analysis revealed an injury-specific stem cell–like OCH subset that was p21 + and highly inflammatory, with a similar inflammatory mesenchymal population (fibro-adipogenic progenitors) evident following muscle injury. Thus, intercommunicating senescent-like neutrophils and mesenchymal progenitor cells were key regulators of tissue repair in bone and potentially across tissues. Moreover, our findings established contextual roles of p21 + versus p16 + senescent/senescent-like cells that may be leveraged for therapeutic opportunities.

Abstract Background: In breast cancer, the spatial relationship between immune and tumor cells is increasingly recognized as critical in determining the efficacy of neoadjuvant therapy (NAT). This study investigated how the distribution of immune cells, particularly CD8+ T cells, relative to tumor cells affects treatment outcomes. Methods: Biopsies from 104 breast cancer patients were examined, both pre- and post-NAT, using multiplex immunohistochemistry (mIHC). This study focused on the density and distribution of CD8+ T cells, CD68+ macrophages, FoxP3+ regulatory T cells, and other immune markers. Results: The spatial proximity of CD8+ T cells within 20 µm of cancer cells (N20-CD8+T) was strongly correlated with improved clinical outcomes across diverse tumor subtypes and NAT regimens. A significant post-NAT decrease in CD4+, CD68+, and FoxP3+ cells highlights notable shifts in the tumor immune landscape. A noteworthy finding was the positive correlation between CXCL9 expression and N20-CD8+T cells, suggesting a mechanism for immune cell recruitment and interaction within the tumor microenvironment. These results highlight the complex interplay among NAT, immune cell modifications, and patient outcomes. Conclusions: This study revealed that the proximity of N20-CD8+ T cells to tumor cells is consistently associated with favorable NAT outcomes, transcending tumor subtypes, and treatment differences. This highlights the potential of immune cell dynamics, especially CD8+ T cells, as predictive biomarkers for therapeutic responses in breast cancer, underscoring their vital role in tumor immunity.

Chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of neurological autoimmune diseases is promising, but CAR T cell kinetics and immune alterations after treatment are poorly understood. Here, we performed single-cell multi-omics sequencing of paired cerebrospinal fluid (CSF) and blood samples from patients with neuromyelitis optica spectrum disorder (NMOSD) treated with anti–B cell maturation antigen (BCMA) CAR T cells. Proliferating cytotoxic-like CD8 + CAR T cell clones were identified as the main effectors in autoimmunity. Anti-BCMA CAR T cells with enhanced features of chemotaxis efficiently crossed the blood-CSF barrier, eliminated plasmablasts and plasma cells in the CSF, and suppressed neuroinflammation. The CD44-expressing early memory phenotype in infusion products was potentially associated with CAR T cell persistence in autoimmunity. Moreover, CAR T cells from patients with NMOSD displayed distinctive features of suppressed cytotoxicity compared with those from hematological malignancies. Thus, we provide mechanistic insights into CAR T cell function in patients with neurological autoimmune disease.

AbstractThe objective of the current study is to develop a new method for tracking transplanted human induced pluripotent stem cells‐derived cardiomyocytes (hiPSC‐CMs) using magnetic resonance imaging (MRI). The CRISPR/dCas9 activation system is employed to overexpress ferritin heavy chain (FHC) in hiPSC‐CMs. The mRNA and protein expression of FHC in hiPSC and hiPSC‐CMs significantly increased after transfection. Iron chloride does not affect the cell viability in a concentration range from 0 to 2000 µm. hiPSCs overexpressing FHC (hiPSC‐ FHCOE) and hiPSC‐CMs overexpressing FHC (hiPSC‐CM‐FHCOE) significantly enhanced cellular uptake of iron chloride but with no changes in electrophysiological properties compared to hiPSC‐CM‐Control. Furthermore, hiPSC‐CM‐FHCOE presented robust contrast and lower T2* values, signifying their potential as highly effective candidates for cardiac MRI. Next, hiPSC‐CM‐FHCOE is injected into mouse hearts and after 3 days of transplantation, MR images are obtained. hiPSC‐CM‐FHCOE cells exhibited clear signals in the hearts with lower T2* and rapid signal decay. Collectively, data from this proof‐of‐concept study demonstrated that endogenous labeling with FHC in hiPSC‐CMs can be a potent strategy for enhancing the accuracy of cardiac MRI. This technology represents a significant step forward in tracking the transplanted hiPSC‐CMs in the hearts of live animals.

Study Design: Retrospective analysis of a prospective, multicenter registry. Objective: To assess whether upper or lower limb mJOA improvement more strongly associates with patient satisfaction after surgery for cervical spondylotic myelopathy (CSM). Summary of Background Data: The modified Japanese Orthopaedic Association (mJOA) is commonly used to assess functional status in patients with CSM. Patients present with upper and/or lower extremity dysfunction, and it is unclear whether improvement in one and/or both symptoms drives postoperative patient satisfaction. Methods: This study utilizes the prospective Quality Outcomes Database (QOD) CSM data set. Clinical outcomes included mJOA and North American Spine Society (NASS) satisfaction. The upper limb mJOA score was defined as upper motor plus sensory mJOA, and the lower limb mJOA as lower motor plus sensory mJOA. Ordered logistic regression was used to determine whether upper or lower limb mJOA was more closely associated with NASS satisfaction, adjusting for other covariates. Results: Overall, 1141 patients were enrolled in the QOD CSM cohort. In all, 780 had both preoperative and 24-month mJOA scores, met inclusion criteria, and were included for analysis. The baseline mJOA was 12.1±2.7, and postoperatively, 85.6% would undergo surgery again (NASS 1 or 2, satisfied). Patients exhibited mean improvement in both upper (baseline:3.9±1.4 vs. 24 mo:5.0±1.1, P<0.001) and lower limb mJOA (baseline:3.9±1.4 vs. 24 mon:4.5±1.5, P<0.001); however, the 24-month change in the upper limb mJOA was greater (upper:1.1±1.6 vs. lower:0.6±1.6, P<0.001). Across 24-month NASS satisfaction, the baseline upper and lower limb mJOA scores were similar (pupper=0.28, plower=0.092). However, as satisfaction decreased, the 24-month change in upper and lower limb mJOA decreased as well (pupper<0.001, plower<0.001). Patients with NASS scores of 4 (lowest satisfaction) did not demonstrate significant differences from baseline in upper or lower limb mJOA (P>0.05). In ordered logistic regression, NASS satisfaction was independently associated with upper limb mJOA improvement (OR=0.81; 95% CI: 0.68-0.97; P=0.019) but not lower limb mJOA improvement (OR=0.84; 95% CI: 0.70-1.0; P=0.054). Conclusions: As the magnitude of upper and lower mJOA improvement decreased postoperatively, so too did patient satisfaction with surgical intervention. Upper limb mJOA improvement was a significant independent predictor of patient satisfaction, whereas lower limb mJOA improvement was not. These findings may aid preoperative counseling, stratified by patients’ upper and lower extremity treatment expectations. Level of Evidence: Level—III.

OBJECTIVE The objective of this study was to compare clinical and patient-reported outcomes (PROs) between posterior foraminotomy and anterior cervical discectomy and fusion (ACDF) in patients presenting with cervical radiculopathy. METHODS The Quality Outcomes Database was queried for patients who had undergone ACDF or posterior foraminotomy for radiculopathy. To create two highly homogeneous groups, optimal individual matching was performed at a 5:1 ratio between the two groups on 29 baseline variables (including demographic characteristics, comorbidities, symptoms, patient-reported scores, underlying pathologies, and levels treated). Outcomes of interest were length of stay, reoperations, patient-reported satisfaction, increase in EQ-5D score, and decrease in Neck Disability Index (NDI) scores for arm and neck pain as long as 1 year after surgery. Noninferiority analysis of achieving patient satisfaction and minimal clinically important difference (MCID) in PROs was performed with an accepted risk difference of 5%. RESULTS A total of 7805 eligible patients were identified: 216 of these underwent posterior foraminotomy and were matched to 1080 patients who underwent ACDF. The patients who underwent ACDF had more underlying pathologies, lower EQ-5D scores, and higher NDI and neck pain scores at baseline. Posterior foraminotomy was associated with shorter hospitalization (0.5 vs 0.9 days, p < 0.001). Reoperations within 12 months were significantly more common among the posterior foraminotomy group (4.2% vs 1.9%, p = 0.04). The two groups performed similarly in PROs, with posterior foraminotomy being noninferior to ACDF in achieving MCID in EQ-5D and neck pain scores but also having lower rates of maximal satisfaction at 12 months (North American Spine Society score of 1 achieved by 65.2% posterior foraminotomy patients vs 74.6% of ACDF patients, p = 0.02). CONCLUSIONS The two procedures were found to be offered to different populations, with ACDF being selected for patients with more complicated pathologies and symptoms. After individual matching, posterior foraminotomy was associated with a higher reoperation risk within 1 year after surgery compared to ACDF (4.2% vs 1.9%). In terms of 12-month PROs, posterior foraminotomy was noninferior to ACDF in improving quality of life and neck pain. The two procedures also performed similarly in improving NDI scores and arm pain, but ACDF patients had higher maximal satisfaction rates.