Is Upper Extremity or Lower Extremity Function More Important for Patient Satisfaction? An Analysis of 24-Month Outcomes from the QOD Cervical Spondylotic Myelopathy Cohort.

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.

Perioperative Management and Outcomes in Patients Receiving Low-dose Rivaroxaban and or Aspirin: A Sub-analysis of the COMPASS Trial.

BACKGROUND: No study has investigated the perioperative management and clinical outcomes in patients who are receiving rivaroxaban 2.5 mg bid and ASA 81-100 mg daily. METHODS: Sub-analysis of the COMPASS trial to assess perioperative management and clinical outcomes in patients with stable coronary or peripheral artery disease who were randomized to receive rivaroxaban 2.5 mg bid plus ASA 100 mg daily, rivaroxaban 5 mg bid, or ASA 100 mg daily. Patients studied required a surgery/procedure during the trial. The study outcomes, which included myocardial infarction, angina, stroke, acute limb ischemia, bleeding, and death, were assessed according to treatment allocation. RESULTS: There were 2,632 patients studied (mean age, 68 years; 80% male) who had a surgery/procedure, comprising percutaneous coronary interventions (∼43%), carotid or other arterial angioplasty (∼15%), pacemaker or internal cardiac defibrillator implantation (∼9%), and coronary artery bypass graft surgery (∼7%). Perioperative study drug management varied, with about one-third of patients not interrupting study drug and the remainder interrupting it between 1 and ≥10 days pre-procedure. The incidences of adverse outcomes across treatment groups were 12.7% to 15.3% for myocardial ischemia, 0.8% to 1.2% for stroke, 0.1% to 0.2% for venous thromboembolism, and 3.1% to 4.2% for any bleeding. There was no statistically significant difference in outcome rates across treatment groups. CONCLUSION: In patients in the COMPASS trial who required a surgery/procedure, there was no significant difference in perioperative adverse outcomes whether patients were receiving rivaroxaban 2.5 mg bid and ASA 100 mg daily, rivaroxaban 5 mg bid or ASA alone.

Surgical Management of Thoracolumbar Adjacent Segment Disease: Techniques and Outcomes in 107 Patients Undergoing Surgical Intervention.

BACKGROUND: Adjacent segment disease (ASD) is a known sequela of thoracolumbar instrumented fusions. Various surgical options are available to address ASD in patients with intractable symptoms who have failed conservative measures. However, the optimal treatment strategy for symptomatic ASD has not been established. We examined several clinical outcomes utilizing different surgical interventions for symptomatic ASD. METHODS: A retrospective review was performed for a consecutive series of patients undergoing revision surgery for thoracolumbar ASD between October 2011 and February 2022. Patients were treated with endoscopic decompression (N = 17), microdiscectomy (N = 9), lateral lumbar interbody fusion (LLIF; N = 26), or open laminectomy and fusion (LF; N = 55). The primary outcomes compared between groups were re-operation rates and numeric pain scores for leg and back at 2 weeks, 10 weeks, 6 months, and 12 months postoperation. Secondary outcomes included time to re-operation, estimated blood loss, and length of stay. RESULTS: Of the 257 patients who underwent revision surgery for symptomatic ASD, 107 patients met inclusion criteria with a minimum of 1-year follow-up. The mean age of all patients was 67.90 ± 10.51 years. There was no statistically significant difference between groups in age, gender, preoperative American Society of Anesthesiologists scoring, number of previously fused levels, or preoperative numeric leg and back pain scores. The re-operation rates were significantly lower in LF (12.7%) and LLIF cohorts (19.2%) compared with microdiscectomy (33%) and endoscopic decompression (52.9%; P = 0.005). Only LF and LLIF cohorts experienced significantly decreased pain scores at all 4 follow-up visits (2 weeks, 10 weeks, 6 months, and 12 months; P < 0.001 and P < 0.05, respectively) relative to preoperative scores. CONCLUSION: Symptomatic ASD often requires treatment with revision surgery. Fusion surgeries (either stand-alone lateral interbody or posterolateral with instrumentation) were most effective and durable with respect to alleviating pain and avoiding additional revisions within the first 12 months following revision surgery. CLINICAL RELEVANCE: This study emphasizes the importance of risk-stratifying patients to identify the least invasive approach that treats their symptoms and reduces the risk of future surgeries.

Staged Versus Same-Day Surgery in Circumferential Minimally Invasive Deformity Correction.

BACKGROUND AND OBJECTIVES: We sought to compare long-term clinical and radiographic outcomes in patients who underwent staged vs same-day circumferential minimally invasive surgery (cMIS) for adult spinal deformity (ASD). METHODS: We reviewed staged and same-day cMIS ASD cases in a prospective multi-institution database to compare preoperative and 2-year clinical and radiographic parameters between cohorts. RESULTS: A total of 85 patients with a 2-year follow-up were identified (27 staged, 58 same-day). Staged patients had more extensive surgeries and greater hospital length of stay (all P < .001). There were no significant differences in preoperative or 2-year postoperative clinical metrics between cohorts. Patients in the staged cohort also had greater preoperative coronal deformity and thus experienced greater reduction in coronal deformity at 2 years (all P < .01). CONCLUSION: Patients undergoing staged or same-day cMIS correction had similar outcomes at 2 years postoperatively. Staged cMIS ASD correction may be more appropriate in patients with greater deformity, higher frailty, and who require longer, more extensive surgeries.

Acalabrutinib plus venetoclax and rituximab in treatment-naive mantle cell lymphoma: 2-year safety and efficacy analysis.

This phase 1b study (NCT02717624) evaluated the safety and efficacy of acalabrutinib, venetoclax, and rituximab (AVR) in treatment-naive mantle cell lymphoma (TN MCL). Patients received acalabrutinib from cycle 1 until progressive disease or undue toxicity, rituximab for 6 cycles with maintenance every other cycle through cycle 24 or until progressive disease, and venetoclax, beginning at cycle 2, for 24 cycles. Twenty-one patients were enrolled, 95.2% completed induction (6 AVR cycles), and 47.6% continued maintenance with acalabrutinib. Thirteen (61.9%) patients had grade 3-4 adverse events (AEs), most commonly neutropenia (33.3%). Seven (33.3%) patients had COVID-19 infection (6 [28.6%] serious AEs; 5 [23.8%] deaths, all among unvaccinated patients). There were no grade ≥ 3 events of atrial fibrillation, ventricular tachyarrhythmias, major hemorrhages, or tumor lysis syndrome. Overall response rate (ORR) by Lugano criteria was 100% (95% confidence interval [CI]: 83.9, 100.0) with 71.4% complete response (CR). With median follow-up of 27.8 months, median progression-free survival (PFS) and overall survival (OS) were not reached. PFS rates at 1 and 2 years were 90.5% (95% CI: 67.0, 97.5) and 63.2% (34.7, 82.0), respectively; both were 95% after censoring COVID-19 deaths. OS rates at 1 and 2 years were 95.2% (95% CI: 70.7, 99.3) and 75.2% (50.3, 88.9), respectively; both were 100% after censoring COVID-19 deaths. Overall, 87.5% of patients with available minimal residual disease (MRD) data achieved MRD negativity (10-6; next-generation sequencing) during treatment. AVR represents a chemotherapy-free regimen for TN MCL and resulted in high ORR and high rates of MRD negativity.

Impact of Demographics and Neighborhood Socioeconomic Variables on Clinical Trial Participation in Non-Hodgkin Lymphoma.

Prior studies have demonstrated that certain populations including older patients, racial/ethnic minority groups, and women are underrepresented in clinical trials. We performed a retrospective analysis of patients with Non-Hodgkin Lymphoma (NHL) seen at MD Anderson Cancer Center (MDACC) to investigate the association between trial participation, race/ethnicity, travel distance and neighborhood socioeconomic status (nSES). Using patient addresses, we ascertained nSES variables on educational attainment, income, poverty, racial composition and housing at the census tract (CT) level. We also performed geospatial analysis to determine the geographic distribution of clinical trial participants and distance from patient residence to MDACC. We examined 3146 consecutive adult patients with NHL seen between January 2017 and December 2020. The study cohort was predominantly male and non-Hispanic white (NHW). The most common insurance types were private insurance and Medicare; only 1.1% of patients had Medicaid. There was a high overall participation rate of 30.5% with 20.9% enrolled in therapeutic trials. In univariate analyses, lower participation rates were associated with lower nSES including higher poverty rates and living in crowded households. Racial composition of CT was not associated with differences in trial participation. In multivariable analysis, trial participation varied significantly by histology and participation declined nonlinearly with age in the overall, follicular lymphoma and diffuse large B-cell lymphoma (DLBCL) models. In the DLBCL subset, Hispanic patients had lower odds of participation than Whites (odds ratio 0.36 [95% confidence interval 0.21 - 0.62 p=0.001). In our large academic cohort, race, gender, insurance type, and nSES were not associated with trial participation, whereas age and diagnosis were.

Ultrasound Surveillance in Melanoma Management: Bridging Diagnostic Promise with Real-World Adherence: A Systematic Review and Meta-Analysis.

BACKGROUND: Ultrasound surveillance has become the new standard of care in stage III melanoma after the 2017 Multicenter Selective Lymphadenectomy Trial II (MSLT-II) demonstrated non-inferior 3-year survival compared with complete lymph node dissection. OBJECTIVE: We aimed to quantify diagnostic performance and adherence rates of ultrasound surveillance for melanoma locoregional metastasis, offering insights into real-world applicability. METHODS: Conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, we systematically searched the Medline, Embase, Cochrane Library, CINAHL, Scopus, and Web of Science databases from inception until 11 October 2023. All primary studies that reported data on the diagnostic performance or adherence rates to ultrasound surveillance in melanoma were included. R statistical software was used for data synthesis and analysis. Sensitivity and specificity were aggregated across studies using the meta-analytic method for diagnostic tests outlined by Rutter and Gatsonis. Adherence rates were calculated as the ratio of patients fully compliant to planned follow-up to those who were not. RESULTS: A total of 36 studies including 18,273 patients were analysed, with a mean age of 56.6 years and a male-to-female ratio of 1:1.11. The median follow-up duration and frequency was 36 and 4 months, respectively. The pooled sensitivity of ultrasound examination was 0.879 (95% confidence interval [CI] 0.878-0.879) and specificity was 0.969 (95% CI 0.968-0.970), representing a diagnostic odds ratio of 224.5 (95% CI 223.1-225.9). Ultrasound examination demonstrated a substantial improvement in absolute sensitivity over clinical examination alone, with a number needed to screen (NNS) of 2.95. The overall adherence rate was 77.0% (95% CI 76.0-78.1%), with significantly lower rates in the United States [US] (p <  0.001) and retrospective studies (p <  0.001). CONCLUSION: Ultrasound is a powerful diagnostic tool for locoregional melanoma metastasis. However, the real applicability to surveillance programmes is limited by low adherence rates, especially in the US. Further studies should seek to address this adherence gap.

Comparing posterior cervical foraminotomy with anterior cervical discectomy and fusion in radiculopathic patients: an analysis from the Quality Outcomes Database.

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.

Three-year outcomes of valoctocogene roxaparvovec gene therapy for hemophilia A.

BACKGROUND: Valoctocogene roxaparvovec transfers a human factor (F)VIII coding sequence into hepatocytes of people with severe hemophilia A to provide bleeding protection. OBJECTIVES: To present 3-year efficacy and safety in the multicenter, open-label, single-arm, phase 3 GENEr8-1 trial. METHODS: GENEr8-1 enrolled 134 adult males with severe hemophilia A who were receiving FVIII prophylaxis. Efficacy endpoints included annualized bleeding rate, annualized FVIII utilization, FVIII activity (chromogenic substrate assay; imputed as 1 IU/dL at baseline and 0 IU/dL after discontinuation), and the Haemophilia-Specific Quality of Life Questionnaire for Adults. Safety was assessed by adverse events (AEs). RESULTS: At week 156, 131 of 134 participants remained in the study; overall, 17 of 134 resumed prophylaxis. Mean annualized bleeding rate for treated bleeds decreased from 4.8 (SD, 6.5) bleeds/y at baseline to 0.8 (SD, 2.3; P < .0001) bleeds/y after prophylaxis (prophylaxis cessation to last follow-up) and 0.97 (SD, 3.48) bleeds/y during year 3. Annualized FVIII utilization decreased 96.8% from baseline after prophylaxis and 94.2% during year 3. At week 156, mean and median FVIII activity were 18.4 (SD, 30.8) and 8.3 IU/dL, respectively. FVIII activity decrease was lower between years 2 and 3 than between years 1 and 2. At the end of year 3, clinically meaningful improvements in the Haemophilia-Specific Quality of Life Questionnaire for Adults Total Score were observed (mean change from baseline, 6.6; 95% CI, 4.24-8.87; P < .0001). Mild alanine aminotransferase elevations remained the most common AE during year 3 (23.7% of participants). A serious AE of B-cell acute lymphoblastic leukemia was considered unrelated to treatment. CONCLUSION: Hemostatic efficacy was maintained, and safety remained unchanged from previous years.

Inhibition of SRC-3 as a potential therapeutic strategy for aggressive mantle cell lymphoma.

Mantle cell lymphoma (MCL) has a poor prognosis and high relapse rates despite current therapies, necessitating novel treatment regimens. Inhibition of SRC-3 show effectiveness in vivo and in vitro in other B cell lymphomas. Additionally, previous studies have shown that SRC-3 is highly expressed in the lymph nodes of B cell non-Hodgkin's lymphoma patients, suggesting SRC-3 may play a role in the progression of B cell lymphoma. This study aimed to investigate novel SRC-3 inhibitors, SI-10 and SI-12, in mantle cell lymphoma. The cytotoxic effects of SI-10 and SI-12 were evaluated in vitro and demonstrated dose-dependent cytotoxicity in a panel of MCL cell lines. The in vivo efficacy of SI-10 was confirmed in two ibrutinib-resistant models: an immunocompetent disseminated A20 mouse model of B-cell lymphoma and a human PDX model of MCL. Notably, SI-10 treatment also resulted in a significant extension of survival in vivo with low toxicity in both ibrutinib-resistant murine models. We have investigated SI-10 as a novel anti-lymphoma compound via the inhibition of SRC-3 activity. These findings indicate that targeting SRC-3 should be investigated in combination with current clinical therapeutics as a novel strategy to expand the therapeutic index and to improve lymphoma outcomes.

TP53 mutation is frequent in mantle cell lymphoma with EZH2 expression and have dismal outcome when both are present.

Enhancer of zeste homolog 2 (EZH2) expression is found in about 40% of mantle cell lymphoma (MCL) patients, which is associated with aggressive histology, high Ki-67 proliferation rate, p53 mutant pattern and inferior overall survival (OS). We conducted 11-gene (ATM, BIRC3, CCND1, KMT2C, KMT2D, NOTCH1, NOTCH2, RB1, TP53, TRAF2 and UBR5) next generation sequencing panel to shed more light on MCL with EZH2 expression (EZH2+ MCL). EZH2+ MCL more frequently harbor TP53 mutation compared to EZH2(-) MCL (41.2% vs. 19.1%, respectively, p = 0.045). TP53 mutation and EZH2 expression demonstrated overlapping features including aggressive histology, high Ki-67 proliferation rate and p53 mutant pattern by immunohistochemistry. Comparative analysis disclosed that EZH2 expression correlates with high Ki-67 proliferation rate irrespective of TP53 mutation. Aggressive histology is associated with EZH2 expression or TP53 mutation, possibly via independent mechanisms. p53 mutant pattern is due to TP53 mutation. MCL patients with EZH2 expression or TP53 mutation show inferior outcome and when both are present, patients have dismal outcome.

Deep learning on pre-procedural computed tomography and clinical data predicts outcome following stroke thrombectomy.

BACKGROUND: Deep learning using clinical and imaging data may improve pre-treatment prognostication in ischemic stroke patients undergoing endovascular thrombectomy (EVT). METHODS: Deep learning models were trained and tested on baseline clinical and imaging (CT head and CT angiography) data to predict 3-month functional outcomes in stroke patients who underwent EVT. Classical machine learning models (logistic regression and random forest classifiers) were constructed to compare their performance with the deep learning models. An external validation dataset was used to validate the models. The MR PREDICTS prognostic tool was tested on the external validation set, and its performance was compared with the deep learning and classical machine learning models. RESULTS: A total of 975 patients (550 men; mean±SD age 67.5±15.1 years) were studied with 778 patients in the model development cohort and 197 in the external validation cohort. The deep learning model trained on baseline CT and clinical data, and the logistic regression model (clinical data alone) demonstrated the strongest discriminative abilities for 3-month functional outcome and were comparable (AUC 0.811 vs 0.817, Q=0.82). Both models exhibited superior prognostic performance than the other deep learning (CT head alone, CT head, and CT angiography) and MR PREDICTS models (all Q<0.05). CONCLUSIONS: The discriminative performance of deep learning for predicting functional independence was comparable to logistic regression. Future studies should focus on whether incorporating procedural and post-procedural data significantly improves model performance.

Mainstream Model of Genetic Testing for Prostate Cancer at a Large Tertiary Cancer Centre.

BACKGROUND: An estimated 20% to 30% of men with advanced prostate cancer carry a mutation in DNA damage repair genes, of which half are estimated to be germline. Eligibility criteria for germline genetic testing expanded significantly for Ontario patients in May 2021 and many centers adopted a "mainstream" model, defined as oncologist-initiated genetic testing. METHODS: We conducted a retrospective chart review to report on the first-year mainstream experience of a large tertiary oncologic center, the Sunnybrook Odette Cancer Centre. All patients who underwent mainstream at the discretion of their treating physician were included. A subset underwent somatic profiling as part of clinical trial screening. Descriptive statistics were used to report baseline clinicopathologic characteristics and treatments received. RESULTS: Between May 1, 2021, and May 30, 2022, 174 patients with prostate cancer underwent mainstream germline genetic testing with a 19-gene panel. Median age was 75 (IQR 68-80), and 82% of patients were diagnosed with either de novo metastatic or high-risk localized prostate adenocarcinoma. Fourteen patients (8%; 95% CI 4%-12%) were found to have a deleterious germline mutation, including pathogenic or likely pathogenic variants in BRCA1/2, ATM, CHEK2, PMS2, RAD51C, HOXB13, and BRIP1. Forty-nine patients (28%; 95% CI 21%-35%) were found to have a variant of uncertain significance. Thirty-four patients also had next-generation sequencing (NGS) of their somatic tissue. Among this subset, 8 of 34 (23%) had an alteration in homologous recombination repair (HRR) genes. Of the 14 patients with a germline mutation, none had a prior personal history of malignancy and 6 (43%) did not have any first- or second-degree relatives with history of prostate, pancreatic, breast, or ovarian cancer. CONCLUSION: We report on the real-world characteristics of prostate cancer patients who underwent mainstream germline genetic testing. Personal history and family history of cancer cannot reliably stratify patients for the presence of pathogenic germline variants.

What is the effect of preoperative depression on outcomes after minimally invasive surgery for adult spinal deformity? A prospective cohort analysis.

OBJECTIVE: Depression has been implicated with worse immediate postoperative outcomes in adult spinal deformity (ASD) correction, yet the specific impact of depression on those patients undergoing minimally invasive surgery (MIS) requires further clarity. This study aimed to evaluate the role of depression in the recovery of patients with ASD after undergoing MIS. METHODS: Patients who underwent MIS for ASD with a minimum postoperative follow-up of 1 year were included from a prospectively collected, multicenter registry. Two cohorts of patients were identified that consisted of either those affirming or denying depression on preoperative assessment. The patient-reported outcome measures (PROMs) compared included scores on the Oswestry Disability Index (ODI), numeric rating scale (NRS) for back and leg pain, Scoliosis Research Society Outcomes Questionnaire (SRS-22), SF-36 physical component summary, SF-36 mental component summary (MCS), EQ-5D, and EQ-5D visual analog scale. RESULTS: Twenty-seven of 147 (18.4%) patients screened positive for preoperative depression. The nondepressed cohort had an average of 4.83 levels fused, and the depressed cohort had 5.56 levels fused per patient (p = 0.267). At 1-year follow-up, 10 patients still reported depression, representing a 63% decrease. Postoperatively, both cohorts demonstrated improvement in their PROMs; however, at 1-year follow-up, those without depression had statistically better outcomes based on the EQ-5D, MCS, and SRS-22 scores (p < 0.05). Patients with depression continued to experience higher NRS leg scores at 1-year follow-up (3.63 vs 2.22, p = 0.018). After controlling for covariates, the authors found that depression significantly impacted only 1-year follow-up MCS scores (ß = 8.490, p < 0.05). CONCLUSIONS: Depressed and nondepressed patients reported similar improvements after MIS surgery, except MCS scores were more likely to improve in nondepressed patients.

Cervical spondylotic myelopathy and driving abilities: defining the prevalence and long-term postoperative outcomes using the Quality Outcomes Database.

OBJECTIVE: Cervical spondylotic myelopathy (CSM) can cause significant difficulty with driving and a subsequent reduction in an individual's quality of life due to neurological deterioration. The positive impact of surgery on postoperative patient-reported driving capabilities has been seldom explored. METHODS: The CSM module of the Quality Outcomes Database was utilized. Patient-reported driving ability was assessed via the driving section of the Neck Disability Index (NDI) questionnaire. This is an ordinal scale in which 0 represents the absence of symptoms while driving and 5 represents a complete inability to drive due to symptoms. Patients were considered to have an impairment in their driving ability if they reported an NDI driving score of 3 or higher (signifying impairment in driving duration due to symptoms). Multivariable logistic regression models were fitted to evaluate mediators of baseline impairment and improvement at 24 months after surgery, which was defined as an NDI driving score < 3. RESULTS: A total of 1128 patients who underwent surgical intervention for CSM were included, of whom 354 (31.4%) had baseline driving impairment due to CSM. Moderate (OR 2.3) and severe (OR 6.3) neck pain, severe arm pain (OR 1.6), mild-moderate (OR 2.1) and severe (OR 2.5) impairment in hand/arm dexterity, severe impairment in leg use/walking (OR 1.9), and severe impairment of urinary function (OR 1.8) were associated with impaired driving ability at baseline. Of the 291 patients with baseline impairment and available 24-month follow-up data, 209 (71.8%) reported postoperative improvement in their driving ability. This improvement seemed to be mediated particularly through the achievement of the minimal clinically important difference (MCID) in neck pain and improvement in leg function/walking. Patients with improved driving at 24 months noted higher postoperative satisfaction (88.5% vs 62.2%, p < 0.01) and were more likely to achieve a clinically significant improvement in their quality of life (50.7% vs 37.8%, p < 0.01). CONCLUSIONS: Nearly one-third of patients with CSM report impaired driving ability at presentation. Seventy-two percent of these patients reported improvements in their driving ability within 24 months of surgery. Surgical management of CSM can significantly improve patients' driving abilities at 24 months and hence patients' quality of life.

The HSP90-MYC-CDK9 network drives therapeutic resistance in mantle cell lymphoma.

Brexucabtagene autoleucel CAR-T therapy is highly efficacious in overcoming resistance to Bruton's tyrosine kinase inhibitors (BTKi) in mantle cell lymphoma. However, many patients relapse post CAR-T therapy with dismal outcomes. To dissect the underlying mechanisms of sequential resistance to BTKi and CAR-T therapy, we performed single-cell RNA sequencing analysis for 66 samples from 25 patients treated with BTKi and/or CAR-T therapy and conducted in-depth bioinformatics™ analysis. Our analysis revealed that MYC activity progressively increased with sequential resistance. HSP90AB1 (Heat shock protein 90 alpha family class B member 1), a MYC target, was identified as early driver of CAR-T resistance. CDK9 (Cyclin-dependent kinase 9), another MYC target, was significantly upregulated in Dual-R samples. Both HSP90AB1 and CDK9 expression were correlated with MYC activity levels. Pharmaceutical co-targeting of HSP90 and CDK9 synergistically diminished MYC activity, leading to potent anti-MCL activity. Collectively, our study revealed that HSP90-MYC-CDK9 network is the primary driving force of therapeutic resistance.

A meta-analysis comparing efficacy and safety between proton beam therapy versus carbon ion radiotherapy.

BACKGROUND: This study aimed to compare the outcomes of proton beam therapy (PBT) and carbon ion radiotherapy (CIRT) by a systematic review and meta-analysis of the existing clinical evidence. METHODS: A systematic literature search was performed to identify studies comparing the clinical outcomes of PBT and CIRT. The included studies were required to report oncological outcomes (local control [LC], progression-free survival [PFS], or overall survival [OS]) or adverse events. RESULTS: Eighteen articles comprising 1857 patients (947 treated with PBT and 910 treated with CIRT) were included in the analysis. The pooled analysis conducted for the overall population yielded average hazard ratios of 0.690 (95% confidence interval (CI), 0.493-0.967, p = 0.031) for LC, 0.952 (95% CI, 0.604-1.500, p = 0.590) for PFS, and 1.183 (0.872-1.607, p = 0.281) for OS with reference to CIRT. The subgroup analyses included patients treated in the head and neck, areas other than the head and neck, and patients with chordomas and chondrosarcomas. These analyses revealed no significant differences in most outcomes, except for LC in the subgroup of patients treated in areas other than the head and neck. Adverse event rates were comparable in both groups, with an odds ratio (OR) of 1.097 (95% CI, 0.744-1.616, p = 0.641). Meta-regression analysis for possible heterogeneity did not demonstrate a significant association between treatment outcomes and the ratio of biologically effective doses between modalities. CONCLUSION: This study highlighted the comparability of PBT and CIRT in terms of oncological outcomes and adverse events.

Ophthalmic artery stenosis on three-dimensional rotational angiography: Interrater agreement, prevalence, and risk factors.

BACKGROUND: There is emerging interest in ophthalmic artery (OA) stenosis angioplasty for the treatment of age-related macular degeneration. Three-dimensional rotational angiography (3DRA) could be used during conventional angiography to determine the presence and severity of OA stenosis. In patients who had undergone 3DRA of the internal carotid artery, we aimed to assess the interrater agreement, prevalence, and risk factors for OA stenosis. METHODS: Consecutive patients from two centers who had undergone conventional angiography with 3DRA of the internal carotid arteries were enrolled in this study. 3DRAs were independently double read for the presence of OA stenosis, as defined as narrowing of the proximal OA of at least 50% when compared to the more distal "normal" OA. Interrater agreement for the evaluation of OA stenosis was assessed with the Cohen's kappa coefficient. Univariate and multivariable logistic regression were used to identify potential predictors of OA stenosis. RESULTS: Three hundred and two patients (97 men; mean ± SD 57.6 ± 13.4 years) were included in the analysis. Cohen's kappa coefficient (95% CI) was 0.877 (0.798-0.956). OA stenosis was present in 45 patients (14.9%). Multiple logistic regression demonstrated that female sex (odds ratio [OR] = 2.70, 95% confidence interval [CI] 1.18-6.09, p = 0.02) and smoking (OR = 2.11, 95% CI 1.10-4.06, p = 0.03) were significant risk factors for OA stenosis. Age, hypertension, diabetes, coronary artery disease, and subarachnoid hemorrhage were not associated with OA stenosis. CONCLUSION: The evaluation of OA stenosis on 3DRA had excellent interrater agreement. OA stenosis was common and was associated with smoking and female sex.