Citations

Abstract Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) have a propensity to transform to an accelerated or blast phase (MPN-AP/BP). The resulting disease has clinically similar manifestations to Acute Myeloid Leukemia (AML) but worse clinical outcomes. Here we present the first comprehensive description of the transcriptomic characteristics of MPN-AP/BP. Our analysis incorporates data from 261 patients of the BeatAML cohort and 56 MPN-AP/BP patients, 11 of whom had paired samples from before and after transformation. We establish that transformed MPN is a transcriptionally distinct entity from de novo AML and chronic phase MPNs. Genomic pathways traditionally associated with MPN pathogenesis, such as IL2/STAT5 signaling and IL6/JAK/STAT3 signaling were enriched in chronic-phase MPNs but are absent in transformed disease, suggesting JAK2 directed therapy may be less effective in this disease phase. We also discovered that gene expression signatures associated with doxorubicin resistance are highly enriched in transformed MPNs, which may explain the lack of efficacy of standard AML therapies. In addition, we identify that lineage composition at the time of transformation may define distinct subsets of MPN-AP/BP patients, which may assist in the future development of novel treatment strategies.

Abstract OBJECTIVES: · To determine if patients with knee flexion contracture after distal femur fracture have poorer outcomes than patients who regain full knee extension. · To determine if factors such as patient age, gender, open fracture or implant used favors knee flexion contracture. METHODS: Design: Prospective, multicenter trial Setting: Twenty academic level I trauma centers Patient Selection Criteria: Patients with a distal femur fracture. Patients were evaluated for knee flexion contracture at 3, 6 and 12 months post-operatively. Outcome Measures and Comparisons: SMFA, Bother Index and EQ Health Index scores were recorded. Walking and stair climbing ability were assessed. RESULTS: · 126 patients had radiographic follow up for 12 months. There was clinical follow-up for 99 patients at 3 months, 90 patients at 6 months and 74 pts at 12 months. · Patients with full knee extension had better SMFA scores at 12 months than patients with knee flexion contracture (p = 0.308). · Bother Index (p = 0.29) and EQ Health State (p = 0.12) scores did not demonstrate a difference between patients with or without knee flexion contracture at any time point. · Patients with full knee extension had improved walking ability compared to patients with flexion contracture (p = 0.008). Patients with full knee extension had better stair climbing ability than patients with flexion contracture (p = 0.02). · Only older patient age showed a difference in likelihood of flexion contracture (p = 0.01) The rates of flexion contracture in women versus men (p = 0.51), RIMN versus LLP (p = 0.74) and open versus closed fracture (p = 0.24) were not statistically different. CONCLUSIONS: · Patients with knee flexion contractures after distal femur fracture do worse than patients who regain full extension. · Older patients with distal femur fractures are at greater risk for knee flexion contracture. LEVEL OF EVIDENCE: Level I

OBJECTIVE Anterior cervical discectomy and fusion (ACDF) is an established treatment for cervical degenerative disc disease; however, the procedure can cause loss of cervical spine range of motion and potentially accelerate adjacent segment degeneration. Cervical disc arthroplasty (CDA) seeks to preserve native motion of the cervical spine, which can theoretically reduce the incidence of adjacent level degeneration. The literature regarding the relative efficacy of ACDF versus CDA remains inconsistent. In this study, the authors investigate the difference in outcomes between ACDF and CDA and identify factors contributing to the heterogeneity in the literature. METHODS The Ovid, Embase, Scopus, Cochrane, and ClinicalTrials.gov databases were systematically searched from inception to September 5, 2023, for randomized controlled trials (RCTs) comparing ACDF and CDA for degenerative disc disease. Studies were extracted by two authors and verified by a third. Random-effects meta-analysis was performed. The primary outcome was the difference in clinical outcomes between the two surgical groups. The secondary outcomes were the differences in radiological outcomes, surgical characteristics, complication rates, and hospital lengths of stay. The study was registered with the International Prospective Register of Systematic Reviews (PROSPERO; registration no. CRD42023469204) and adhered to the PRISMA guidelines. RESULTS From 584 articles uploaded to the Covidence platform for screening, 35 studies derived from 25 RCTs were included in this systematic review and meta-analysis. A total of 4530 patients were treated with ACDF (2081) and CDA (2449). Forty-six percent of the patients (2063) were male, and the mean age of the study cohort was 45 ± 3 years. In terms of the primary outcome, CDA showed higher rates of neurological and overall success. Regarding the secondary outcomes, CDA demonstrated a significantly lower rate of adjacent level disease, higher rate of heterotopic ossification, and greater range of motion at the operated level. Additionally, CDA had lower rates of reoperation but significantly longer operative times than ACDF. The inclusion of myelopathic patients and variations in follow-up between the surgical groups contributed to the observed effect heterogeneity among studies. CONCLUSIONS In this study, CDA showed comparable or potentially greater success in overall and neurological outcomes, along with a lower incidence of adjacent level degeneration and reoperation rates but longer operative times.

OBJECTIVE The purpose of this study was to evaluate whether level selection for a three-column osteotomy (3CO) impacts cervical deformity correction outcomes, including neurological, radiographic, and patient-reported outcomes. METHODS A retrospective review was performed of patients who underwent a cervical or upper thoracic 3CO for cervical deformity correction by the senior author from 2008 to 2024. Collected outcome measures included neurological outcomes, mechanical complication rates, spinopelvic alignment, and patient-reported outcomes. The minimum follow-up was 1 year. RESULTS One hundred fifteen patients were identified who underwent a cervical or upper thoracic 3CO for cervical deformity correction, of whom 77 met inclusion criteria for this study with a minimum follow-up of 1 year. The median age was 66 years, the median BMI was 27, and 43% of patients were male. Sixteen patients underwent a 3CO at the C7–T1 levels and 61 patients at T2–6 levels. Patients who underwent C7–T1 3CO were more likely to experience a new postoperative neurological deficit compared with those who underwent T2–6 3CO (56% vs 18%, p = 0.004), had less correction in their T1 slope (6° vs 18°, p = 0.027), had less correction in C2–T4 sagittal vertical axis (2.8 cm vs 4.9 cm, p = 0.043), and had a worse Neck Disability Index (NDI) score at 1 year compared with baseline (an increase of 7 vs a decrease of 12, p = 0.033). CONCLUSIONS Cervical deformity patients who underwent a 3CO at C7–T1 had a higher rate of postoperative neurological deficits, less radiographic correction, and worse NDI scores at 1 year compared with patients who underwent a 3CO from T2 to T6. Although 3CO level selection is multifactorial and patient specific, surgeons should consider a 3CO level caudal to T1 when feasible.

OBJECTIVE The evidence on ankylosing spinal disorders (ASDs), including ankylosing spondylitis (AS) and diffuse idiopathic skeletal hyperostosis (DISH), in the context of spinal fracture stems from studies with relatively small sample sizes. There are no studies addressing the patient-reported outcome measures (PROMs) and health-related quality of life (HRQOL) outcomes associated with spinal fracture in this population. The aim of this study was to investigate differences in complications, mortality, PROMs, and HRQOL in patients with and without ASD who had been treated for spinal fracture. METHODS This is a nationwide multicenter retrospective study of prospectively collected data from the Swedish Fracture Register. All patients with fractures of the cervical, thoracic, or lumbar spine treated surgically and conservatively between January 2015 and December 2021 were eligible for inclusion. Two groups of patients were formed based on the presence or absence of concomitant ASD. Primary outcomes of interest included death and PROMs. For surgically treated patients, data on complications and reoperation rates were retrieved. Propensity score matching with a ratio of 1:1 was used to balance the groups prior to intergroup comparison. Variables included in the matching process were age, sex, mechanism of injury, neurological function on admission (Frankel grade), injury type (high vs low energy), fracture type, injured spinal level, time to treatment, and type of treatment (surgical vs conservative). Kaplan-Meier analyses were used to study overall survival following injury. RESULTS A total of 14,604 patients without ASD and 1368 patients with ASD were included in this study. High-energy injuries were less frequent in patients with ASD (13% vs 24%, p < 0.001). Moreover, patients with ASD were less likely to be neurologically intact on admission (90% vs 94%, p < 0.001). There were 1707 surgically treated patients without ASD and 559 with the disorder. After matching, a higher overall risk of reoperation was found among patients with ASD (9.1% vs 3.4%, p = 0.007). Surgical site infections requiring reoperation (p = 0.012), but not construct failure or CSF leakage requiring reoperation (p ≥ 0.05), were more common among the patients with ASD. Postmatching, there were no differences in overall survival between ASD and non-ASD cases (p > 0.05). Moreover, patients with and without ASD had similar PROMs, as indicated by the EQ-5D-3L index at 1 year after injury (p = 0.59). CONCLUSIONS Self-reported recovery 1 year after spinal fracture occurred to a similar extent in patients with and without ASD. Moreover, ASD alone was not a significant risk factor for death. Finally, surgically treated patients with ASD experienced higher rates of postoperative complications and reoperations following surgery.

OBJECTIVE Proximal junctional kyphosis (PJK) affects 5%–61% of patients following thoracolumbar fusion. Many patients are asymptomatic, but a plurality require surgical revision at a cost of $75,000 per case. This analysis sought to analyze the degree to which bone quality and paraspinal muscle sarcopenia influence PJK failure mode. METHODS Patients undergoing thoracolumbar instrumented fusion with an upper instrumented vertebra (UIV) at the thoracolumbar junction (T10–L2) were identified and data were gathered on surgery, bone quality, pre- and postoperative sagittal alignment, and paraspinal muscle cross-sectional area (CSA). PJK was defined as a ≥ 10° increase in proximal junctional angle from the first postoperative radiograph. PJK was classified as discoligamentous failure (type 1), bone failure (type 2), or screw-bone interface failure (type 3) according to the Yagi-Boachie system. Bone quality was assessed by Hounsfield units (HUs) and the vertebral bone quality (VBQ) score at the UIV. RESULTS One hundred fifty patients were identified (median age 67 years, 53.3% female), 46 of whom experienced PJK (22 type 1, 13 type 2, 11 type 3). The median time to onset was most rapid for type 2 events (2.6 months). There were no differences between patients experiencing PJK versus controls regarding bone quality (HUs or VBQ score) or paraspinal muscle CSA on univariate comparison. However, subdivision by PJK type showed patients experiencing bone failure (type 2) PJK had significantly lower HUs at the UIV and UIV+1 relative to those experiencing type 1 PJK or no PJK (all p < 0.05). The VBQ score trended toward being significant, with a higher VBQ score (worse bone quality) in those suffering type 2 PJK, but did not reach statistical significance (p = 0.07). Patients experiencing discoligamentous failure PJK (type 1) had small multifidus CSA (390 mm 2 ) relative to patients experiencing type 2 (516 mm 2 ) or type 3 (440 mm 2 ) PJK and patients who did not experience PJK (481 mm 2 ), although the difference did not reach statistical significance. On time-to-event analysis, low HUs of the UIV/UIV+1 predicted type 2 (hazard ratio [HR] 0.81, 95% CI 0.70–0.93; p = 0.002) and type 2/3 PJK (HR 0.87, 95% CI 0.78–0.96; p = 0.006) but not type 1 PJK. Low UIV multifidus CSA trended toward being a significant predictor of type 1 PJK (HR 0.85, 95% CI 0.69–1.05; p < 0.10). CONCLUSIONS The combination of underlying bone quality and paraspinal musculature CSA at the UIV appeared to influence failure mode among patients who underwent lumbosacral instrumented fusion terminating at the thoracolumbar junction.

OBJECTIVE The landscape of healthcare policies has undergone significant reforms, with a notable shift toward a patient-centered basis. This change has prioritized the use of metrics reflecting subjective patient-reported outcome measures (PROMs). However, these metrics are often limited, especially in terms of determining clinically relevant changes over time. The concept of the minimal clinically important difference (MCID) has been introduced to address this limitation. In this study, the authors aimed to assess the predictive capability of relative change and its corresponding threshold value, the minimal clinically important relative change (MCIRC), as an alternative to the absolute difference and MCID. METHODS Prospectively collected data from 2006 to 2021 were obtained from the Swedish Spine Registry (Swespine). PROMs included the numeric rating scale (NRS) neck and arm pain scores, the EQ-5D index and EQ visual analog scale (VAS), and the Neck Disability Index (NDI). Anchor-based methods were used to determine MCID and MCIRC. Absolute differences and relative changes were compared in terms of predictive power using the area under the receiver operating characteristic curve (AUC). RESULTS A total of 5323 patients were included. The chosen MCID values were −3 for NRS neck pain, −3 for NRS arm pain, 0.08 for EQ-5D index, 13 for EQ VAS, and −30 for NDI scores. The chosen MCIRC values were −40% for NRS neck pain, −50% for arm pain, 323% for EQ-5D index, 55% for EQ VAS, and −33% for NDI scores. Relative change was superior for NRS neck and arm pain scores and NDI, while absolute difference was superior for EQ-5D and EQ VAS scores. CONCLUSIONS Relative change and its corresponding MCIRC were found to be more appropriate as a surrogate of subjective satisfaction when studying the NRS and NDI scores, whereas absolute difference and MCID was more appropriate when addressing EQ-5D index and EQ VAS scores.

OBJECTIVE Artificial intelligence (AI) is increasingly capable of academic writing, with large language models such as ChatGPT showing potential to assist or even generate scientific manuscripts. However, concerns remain regarding the quality, reliability, and interpretive capabilities of AI-generated content. The authors’ study aimed to compare the quality of a human-written versus an AI-generated scientific manuscript to evaluate the strengths and limitations of AI in the context of academic publishing. METHODS Two manuscripts were developed using identical titles, abstracts, and tables of a simulated analysis: one authored by a physician with multiple publications, and the other generated by ChatGPT-4o. Three independent and blinded reviewers—two human and one AI—assessed each manuscript across five domains: clarity and readability, coherence and flow, technical accuracy, depth, and conciseness and precision. Each category was scored on a 10-point scale, and qualitative feedback was collected to highlight specific strengths and weaknesses. Additionally, all reviewers were asked to deduce authorship of the manuscripts. RESULTS The AI-generated manuscript scored higher in clarity and readability (mean 9.0 vs 7.2), but lower in technical accuracy (mean 6.3 vs 9.3) and depth (mean 5.5 vs 7.5). However, reviewers noted that the AI version lacked depth, critical analysis, and contextual interpretation. All reviewers accurately identified the authorship of each manuscript and tended to rate the version more favorably when it aligned with their own origin (human or AI); i.e., human reviewers assigned higher scores to the human-written manuscript, while the AI reviewer scored the AI-generated manuscript higher. CONCLUSIONS Although AI models can improve some aspects of scientific writing, particularly clarity and readability, they fall short in critical reasoning and contextual understanding. This reinforces the importance of human authorship and oversight in maintaining the critical analysis and scientific accuracy essential for academic publishing. AI may be used as a complementary tool to support, rather than replace, human-led scientific writing.

OBJECTIVE Degenerative lumbar spondylolisthesis is a common cause of back and leg pain influenced by factors like instability, disc degeneration, facet arthropathy, and psychosocial phenotype. Patients’ experience of high-severity pain is complex, with significant implications for surgical planning. The goal of this study was to assess the impact of back pain catastrophizing on long-term outcomes following lumbar spondylolisthesis surgery. METHODS This study uses the Quality Outcomes Database (QOD) lumbar spondylolisthesis dataset and includes prospectively collected data from the 12 highest-enrolling clinical sites participating in the QOD lumbar module. The authors reviewed patients undergoing single-segment surgery for grade 1 degenerative lumbar spondylolisthesis. Severe baseline numeric rating scale for back pain (NRS-BP) scores (≥ 8) were classified as "catastrophizing," and mild to moderate pain scores (< 8) were classified as "non-catastrophizing." Patient-reported outcomes (PROs) were compared for catastrophizing versus non-catastrophizing patients at 60 months. Univariate and multivariate analyses were conducted to assess the impact of catastrophizing on PROs, with multivariate analysis controlling for variables initially reaching a p value < 0.10. RESULTS Of the 608 patients in this analysis, 260 (42.8%) experienced catastrophizing while 348 (57.2%) did not. Catastrophizing patients were significantly younger (59.9 ± 12.2 years vs 63.9 ± 11.7 years, p < 0.001), less often had ≥ 4 years of college education (31.2% vs 42.5%, p = 0.004), and more often used private insurance (58.8% vs 47.7%, p = 0.01). The catastrophizing cohort also had higher rates of depression (24.6% vs 17.0%, p = 0.02) and back pain predominance (45.4% vs 32.2%, p < 0.001). Surgical and perioperative characteristics did not significantly differ between cohorts. Although catastrophizing patients typically reported worse PRO scores at both baseline and 60 months, they demonstrated significantly greater improvement and minimal clinically important difference (MCID) achievement across almost all PROs at 60 months (p < 0.05). However, North American Spine Society (NASS) satisfaction scores at 60 months did not differ significantly between cohorts. Multivariate analysis found that catastrophizing significantly predicted 60-month NRS-BP change (β −1.45, 95% CI −1.81 to −1.09; p < 0.001) and MCID achievement (OR 1.98, 95% CI 1.52–2.58; p < 0.001) but not mean NRS-BP score or other metrics, including NASS satisfaction. CONCLUSIONS Despite presenting with worse baseline symptoms, patients with pain catastrophizing experienced substantial and clinically meaningful improvement following surgery for degenerative lumbar spondylolisthesis. Patient satisfaction was comparable between cohorts, reflecting a nuanced balance between greater absolute improvement and persistence of residual symptoms. These findings underscore that catastrophizing should not be viewed as a barrier to surgical success, while pointing to the need for proactive expectation setting and shared decision-making.