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BACKGROUND: The modified Japanese Orthopedic Association (mJOA) score is a widely used and validated metric for assessing severity of myelopathy. Its relationship to functional and quality-of-life outcomes after surgery has not been fully described. OBJECTIVE: To quantify the association of the mJOA with the Neck Disability Index (NDI) and EuroQol-5 Dimension (EQ-5D) after surgery for degenerative cervical myelopathy. METHODS: The cervical module of the prospectively enrolled Quality Outcomes Database was queried retrospectively for adult patients who underwent single-stage degenerative cervical myelopathy surgery. The mJOA score, NDI, and EQ-5D were assessed preoperatively and 3 and 12 months postoperatively. Improvement in mJOA was used as the independent variable in univariate and multivariable linear and logistic regression models. RESULTS: Across 14 centers, 1121 patients were identified, mean age 60.6 ± 11.8 years, and 52.5% male. Anterior-only operations were performed in 772 patients (68.9%). By univariate linear regression, improvements in mJOA were associated with improvements in NDI and EQ-5D at 3 and 12 months postoperatively (all P < .0001) and with improvements in the 10 NDI items individually. These findings were similar in multivariable regression incorporating potential confounders. The Pearson correlation coefficients for changes in mJOA with changes in NDI were −0.31 and −0.38 at 3 and 12 months postoperatively. The Pearson correlation coefficients for changes in mJOA with changes in EQ-5D were 0.29 and 0.34 at 3 and 12 months. CONCLUSION: Improvements in mJOA correlated weakly with improvements in NDI and EQ-5D, suggesting that changes in mJOA may not be a suitable proxy for functional and quality-of-life outcomes.

OBJECTIVE The aim of this study was to determine whether multilevel anterior cervical discectomy and fusion (ACDF) or posterior cervical laminectomy and fusion (PCLF) is superior for patients with cervical spondylotic myelopathy (CSM) and high preoperative neck pain. METHODS This was a retrospective study of prospectively collected data using the Quality Outcomes Database (QOD) CSM module. Patients who received a subaxial fusion of 3 or 4 segments and had a visual analog scale (VAS) neck pain score of 7 or greater at baseline were included. The 3-, 12-, and 24-month outcomes were compared for patients undergoing ACDF with those undergoing PCLF. RESULTS Overall, 1141 patients with CSM were included in the database. Of these, 495 (43.4%) presented with severe neck pain (VAS score > 6). After applying inclusion and exclusion criteria, we compared 65 patients (54.6%) undergoing 3- and 4-level ACDF and 54 patients (45.4%) undergoing 3- and 4-level PCLF. Patients undergoing ACDF had worse Neck Disability Index scores at baseline (52.5 ± 15.9 vs 45.9 ± 16.8, p = 0.03) but similar neck pain (p > 0.05). Otherwise, the groups were well matched for the remaining baseline patient-reported outcomes. The rates of 24-month follow-up for ACDF and PCLF were similar (86.2% and 83.3%, respectively). At the 24-month follow-up, both groups demonstrated mean improvements in all outcomes, including neck pain (p < 0.05). In multivariable analyses, there was no significant difference in the degree of neck pain change, rate of neck pain improvement, rate of pain-free achievement, and rate of reaching minimal clinically important difference (MCID) in neck pain between the two groups (adjusted p > 0.05). However, ACDF was associated with a higher 24-month modified Japanese Orthopaedic Association scale (mJOA) score (β = 1.5 [95% CI 0.5–2.6], adjusted p = 0.01), higher EQ-5D score (β = 0.1 [95% CI 0.01–0.2], adjusted p = 0.04), and higher likelihood for return to baseline activities (OR 1.2 [95% CI 1.1–1.4], adjusted p = 0.002). CONCLUSIONS Severe neck pain is prevalent among patients undergoing surgery for CSM, affecting more than 40% of patients. Both ACDF and PCLF achieved comparable postoperative neck pain improvement 3, 12, and 24 months following 3- or 4-segment surgery for patients with CSM and severe neck pain. However, multilevel ACDF was associated with superior functional status, quality of life, and return to baseline activities at 24 months in multivariable adjusted analyses.

Importance In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P &amp;lt; .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm 2 vs 1.8 [0.6] cm 2 ; P &amp;lt; .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P &amp;lt; .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

OBJECTIVE While surgical decompression is an important treatment modality for cervical spondylotic myelopathy (CSM), it remains unclear if the severity of preoperative myelopathy status affects potential benefit from surgical intervention and when maximum postoperative improvement is expected. This investigation sought to determine if retrospective analysis of prospectively collected patient-reported outcomes (PROs) following surgery for CSM differed when stratified by preoperative myelopathy status. Secondary objectives included assessment of the minimal clinically important difference (MCID). METHODS A total of 1151 patients with CSM were prospectively enrolled from the Quality Outcomes Database at 14 US hospitals. Baseline demographics and PROs at baseline and 3 and 12 months were measured. These included the modified Japanese Orthopaedic Association (mJOA) score, Neck Disability Index (NDI), quality-adjusted life-years (QALYs) from the EQ-5D, and visual analog scale from the EQ-5D (EQ-VAS). Patients were stratified by preoperative myelopathy severity using criteria established by the AO Spine study group: mild (mJOA score 15–17), moderate (mJOA score 12–14), or severe (mJOA score < 12). Univariate analysis was used to identify demographic variables that significantly varied between myelopathy groups. Then, multivariate linear regression and linear mixed regression were used to model the effect of severity and time on PROs, respectively. RESULTS For NDI, EQ-VAS, and QALY, patients in all myelopathy cohorts achieved significant, maximal improvement at 3 months without further improvement at 12 months. For mJOA, moderate and severe myelopathy groups demonstrated significant, maximal improvement at 3 months, without further improvement at 12 months. The mild myelopathy group did not demonstrate significant change in mJOA score but did maintain and achieve higher PRO scores overall when compared with more advanced myelopathy cohorts. The MCID threshold was reached in all myelopathy cohorts at 3 months for mJOA, NDI, EQ-VAS, and QALY, with the only exception being mild myelopathy QALY at 3 months. CONCLUSIONS As assessed by statistical regression and MCID analysis, patients with cervical myelopathy experience maximal improvement in their quality of life, neck disability, myelopathy score, and overall health by 3 months after surgical decompression, regardless of their baseline myelopathy severity. An exception was seen for the mJOA score in the mild myelopathy cohort, improvement of which may have been limited by ceiling effect. The data presented here will aid surgeons in patient selection, preoperative counseling, and expected postoperative time courses.

e19583 Background: Brexucabtagene autoleucel (BA) is an FDA approved therapy for relapsed/refractory (R/R) mantle cell lymphoma (MCL), based on results from ZUMA-2 study. We report the safety and efficacy of BA in standard of care practice among centers in the US Lymphoma CAR-T Consortium. Methods: 16 centers participated in this retrospective study. Patients (pts) who underwent leukapheresis by 12/31/2021 with an intent to manufacture BA were included. Baseline clinical characteristics, bridging therapy, adverse events after BA infusion, and post-infusion outcome data were collected. Eligibility for ZUMA-2 was retrospectively determined. Survival outcomes were analyzed using the Kaplan-Meier method. Results: At the data cut-off date, 189 pts underwent leukapheresis, among whom 167 (88%) completed BA infusion, 22 (12%) did not receive infusion. The median age was 67 years. 16% had high risk simplified MIPI, 57% had Ki-67≥50%, 41% had aggressive histology, 49% had TP53 alteration, 51% with POD24 and 10% had CNS involvement. The median number of prior lines of therapy was 3 (range 1-10). 86% had prior BTKi treatment (89% refractory). 130 (78%) pts would not have met ZUMA-2 eligibility criteria. 113 (68%) pts received bridging therapy, which included BTKi, venetoclax, chemotherapy. Median time from leukapheresis to lymphodepletion chemotherapy: 28 days (range 17-140). Cytokine release syndrome (CRS) rate was 90% (8% grade ≥3; 1 grade 5), and immune effector cell-associated neurotoxicity syndrome (ICANS) rate was 61% (32% grade ≥3). Grade 5 ICANS (n = 0). Medications used to manage CRS and ICANS were 125 (76%) for tocilizumab, 112 (68%) for corticosteroid, and 27 (16%) for anakinra. 32 (20%) pts required ICU admission, 18 pts required vasopressors, and 5 pts required mechanical ventilation. Day 30 response was evaluable in 155 pts (89% ORR, 70% CR). The best ORR was 89%, with 80% CR, 9% PR. The ORR/CR rates were 88%/79% for aggressive histology, 89%/77% for high Ki-67% (> 50%), 90%/72% for TP53 altered, 81%/75% for CNS involved, 89%/79% for BTKi-exposed, 91%/83% for BTKi-naïve, and 89%/78% for those not meeting ZUMA-2 eligibility criteria. The median duration of response was not reached and at 6-month was 67% (95% CI 57-75). With a median follow-up of 5.6 months (range 0.2-15.3), median PFS was not reached, the 6-month PFS rate was 63% (95% CI 54-71), and median OS was 15.3 months and the 6-month OS rate was 85% (95% CI 77-90). Conclusions: This multicenter retrospective study demonstrated encouraging safety and efficacy data of BA in R/R MCL in the real-world practice. Despite 78% of the pts being ineligible for ZUMA-2, the responses, CRS, ICANS and outcomes were comparable to ZUMA-2 data. Long term safety and efficacy will be reported.

The availability of Bruton tyrosine kinase (BTK) inhibitors has brought about a paradigm shift in the treatment of patients with B-cell lymphomas and chronic lymphocytic leukemia. BTK was clinically validated as a target by the efficacy of the first-in-class inhibitor ibrutinib. The extended survival conferred by BTK inhibitors has brought long-term tolerability to the foreground. To minimize toxicities thought to be attributable to off-target kinase inhibition, a next generation of BTK inhibitors with greater selectivity was developed. In the United States, zanubrutinib, a next-generation BTK inhibitor, has been approved for treating adults with mantle cell lymphoma who have received at least one prior therapy, for adults with Waldenström macroglobulinemia, and for adults with relapsed or refractory marginal zone lymphoma who have received at least one anti-CD20–based therapy. Because few head-to-head comparative trials of BTK inhibitors have so far been reported, no BTK ‘inhibitor of choice’ can be identified. Zanubrutinib has promising efficacy in its approved indications and appears to have reduced cardiac toxicities, particularly atrial fibrillation, which may influence the choice of BTK inhibitor treatment by prescribers. Further studies are needed to inform on optimal treatment sequencing of zanubrutinib and its combination with other agents. Here, we summarize existing clinical evidence for its efficacy and safety in mantle cell lymphoma, Waldenström macroglobulinemia, marginal zone lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, and other B-lymphoproliferative indications. Plain Language Summary Zanubrutinib is a drug that was shown to effectively treat cancer of B cells without causing excessive serious side effects Patients with certain B-cell malignancies (cancers of white blood cells) benefit from treatment with Bruton tyrosine kinase (BTK) inhibitors, drugs that block the BTK protein and keep cancer from growing and spreading. Patients experience extended survival with ibrutinib, the first-generation BTK inhibitor approved by US Food and Drug Administration (FDA); however, one in five patients quit treatment because of harmful side effects. Ibrutinib-related side effects such as increased risk of bleeding, atrial fibrillation (abnormal heart rhythm), and high blood pressure are thought to be caused by ibrutinib blocking other proteins besides the intended target protein BTK. To reduce these side effects, zanubrutinib, a next-generation BTK inhibitor, was designed to block BTK more specifically than ibrutinib. Results of clinical studies on zanubrutinib treatment appear promising in patients with several types of B-cell malignancies, including mantle cell lymphoma (MCL), Waldenström macroglobulinemia (WM), marginal zone lymphoma (MZL), chronic lymphocytic leukemia, and small lymphocytic lymphoma. There are not yet enough clinical data to determine which BTK inhibitor is most effective in treating B-cell malignancies without causing harmful side effects. Early data from the phase 3 ALPINE clinical study suggest that zanubrutinib works better than ibrutinib, and fewer patients experience side effects and quit treatment. Zanubrutinib is currently approved for use for treatment of adult patients with MCL who have received at least one prior therapy, for adults with WM, and for adults with MZL who have received at least one anti-CD20–based therapy.

OBJECTIVE Spine surgery represents an ideal target for healthcare cost reduction efforts, with outpatient surgery resulting in significant cost savings. With an increased focus on value-based healthcare delivery, lumbar decompression surgery has been increasingly performed in the outpatient setting when appropriate. The aim of this study was to compare clinical and patient-reported outcomes following outpatient and inpatient lumbar decompression surgery. METHODS The Quality Outcomes Database (QOD) was queried for patients undergoing elective one- or two-level lumbar decompression (laminectomy or laminotomy with or without discectomy) for degenerative spine disease. Patients were grouped as outpatient if they had a length of stay (LOS) < 24 hours and as inpatient if they stayed in the hospital ≥ 24 hours. Patients with ≥ 72-hour stay were excluded from the comparative analysis to increase baseline comparability between the two groups. To create two highly homogeneous groups, optimal matching was performed at a 1:1 ratio between the two groups on 38 baseline variables, including demographics, comorbidities, symptoms, patient-reported scores, indications, and operative details. Outcomes of interest were readmissions and reoperations at 30 days and 3 months after surgery, overall satisfaction, and decrease in Oswestry Disability Index (ODI), back pain, and leg pain at 3 months after surgery. Satisfaction was defined as a score of 1 or 2 in the North American Spine Society patient satisfaction index. Noninferiority of outpatient compared with inpatient surgery was defined as risk difference of < 1.5% at a one-sided 97.5% confidence interval. RESULTS A total of 18,689 eligible one- and two-level decompression surgeries were identified. The matched study cohorts consisted of 5016 patients in each group. Nonroutine discharge was slightly less common in the outpatient group (0.6% vs 0.3%, p = 0.01). The 30-day readmission rates were 4.4% and 4.3% for the outpatient and inpatient groups, respectively, while the 30-day reoperation rates were 1.4% and 1.5%. The 3-month readmission rates were 6.3% for both groups, and the 3-month reoperation rates were 3.1% for the outpatient cases and 2.9% for the inpatient cases. Overall satisfaction at 3 months was 88.8% for the outpatient group and 88.4% for the inpatient group. Noninferiority of outpatient surgery was documented for readmissions, reoperations, and patient-reported satisfaction from surgery. CONCLUSIONS Outpatient lumbar decompression surgery demonstrated slightly lower nonroutine discharge rates in comparison with inpatient surgery. Noninferiority in clinical outcomes at 30 days and 3 months after surgery was documented for outpatient compared with inpatient decompression surgery. Additionally, outpatient decompression surgery performed noninferiorly to inpatient surgery in achieving patient satisfaction from surgery.

OBJECTIVE Cervical spondylotic myelopathy (CSM) is a common progressive spine disorder affecting predominantly middle-aged and elderly populations. With increasing life expectancy, the incidence of CSM is expected to rise further. The outcomes of elderly patients undergoing CSM surgery and especially their quality of life (QOL) postoperatively remain undetermined. This study retrospectively reviewed patients to identify baseline differences and validated postoperative patient-reported outcome (PRO) measures in elderly patients undergoing CSM surgery. METHODS The multi-institutional, neurosurgery-specific NeuroPoint Quality Outcomes Database was queried to identify CSM patients treated surgically at the 14 highest-volume sites from January 2016 to December 2018. Patients were divided into three groups: young (< 65 years), early elderly (65–74 years), and late elderly (≥ 75 years). Demographic and PRO measures (Neck Disability Index [NDI] score, modified Japanese Orthopaedic Association [mJOA] score, EQ-5D score, EQ-5D visual analog scale [VAS] score, arm pain VAS, and neck pain VAS) were compared among the groups at baseline and 3 and 12 months postoperatively. RESULTS A total of 1151 patients were identified: 691 patients (60%) in the young, 331 patients (28.7%) in the early elderly, and 129 patients (11.2%) in the late elderly groups. At baseline, younger patients presented with worse NDI scores (p < 0.001) and lower EQ-5D VAS (p = 0.004) and EQ-5D (p < 0.001) scores compared with early and late elderly patients. No differences among age groups were found in the mJOA score. An improvement of all QOL scores was noted in all age groups. On unadjusted analysis at 3 months, younger patients had greater improvement in arm pain VAS, NDI, and EQ-5D VAS compared with early and late elderly patients. At 12 months, the same changes were seen, but on adjusted analysis, there were no differences in PROs between the age groups. CONCLUSIONS The authors’ results indicate that elderly patients undergoing CSM surgery achieved QOL outcomes that were equivalent to those of younger patients at the 12-month follow-up.

OBJECTIVE Combinations of certain social risk factors of race, sex, education, socioeconomic status (SES), insurance, education, employment, and one’s housing situation have been associated with poorer pain and disability outcomes after lumbar spine surgery. To date, an exploration of such factors in patients with cervical spine surgery has not been conducted. The objective of the current work was to 1) define the social risk phenotypes of individuals who have undergone cervical spine surgery for myelopathy and 2) analyze their predictive capacity toward disability, pain, quality of life, and patient satisfaction–based outcomes. METHODS The Cervical Myelopathy Quality Outcomes Database was queried for the period from January 2016 to December 2018. Race/ethnicity, educational attainment, SES, insurance payer, and employment status were modeled into unique social phenotypes using latent class analyses. Proportions of social groups were analyzed for demonstrating a minimal clinically important difference (MCID) of 30% from baseline for disability, neck and arm pain, quality of life, and patient satisfaction at the 3-month and 1-year follow-ups. RESULTS A total of 730 individuals who had undergone cervical myelopathy surgery were included in the final cohort. Latent class analysis identified 2 subgroups: 1) high risk (non-White race and ethnicity, lower educational attainment, not working, poor insurance, and predominantly lower SES), n = 268, 36.7% (class 1); and 2) low risk (White, employed with good insurance, and higher education and SES), n = 462, 63.3% (class 2). For both 3-month and 1-year outcomes, the high-risk group (class 1) had decreased odds (all p < 0.05) of attaining an MCID score in disability, neck/arm pain, and health-related quality of life. Being in the low-risk group (class 2) resulted in an increased odds of attaining an MCID score in disability, neck/arm pain, and health-related quality of life. Neither group had increased or decreased odds of being satisfied with surgery. CONCLUSIONS Although 2 groups underwent similar surgical approaches, the social phenotype involving non-White race/ethnicity, poor insurance, lower SES, and poor employment did not meet MCIDs for a variety of outcome measures. This finding should prompt surgeons to proactively incorporate socially conscience care pathways within healthcare systems, as well as to optimize community-based resources to improve outcomes and personalize care for populations at social risk.

OBJECTIVE High-impact chronic pain (HICP) is a recently proposed metric that indicates the presence of a severe and troubling pain-related condition. Surgery for cervical spondylotic myelopathy (CSM) is designed to halt disease transition independent of chronic pain status. To date, the prevalence of HICP in individuals with CSM and their HICP transition from presurgery is unexplored. The authors sought to define HICP prevalence, transition, and outcomes in patients with CSM who underwent surgery and identify predictors of these HICP transition groups. METHODS CSM surgical recipients were categorized as HICP at presurgery and 3 months if they exhibited pain that lasted 6–12 months or longer with at least one major activity restriction. HICP transition groups were categorized and evaluated for outcomes. Multivariate multinomial modeling was used to predict HICP transition categorization. RESULTS A majority (56.1%) of individuals exhibited HICP preoperatively; this value declined to 15.9% at 3 months (71.6% reduction). The presence of HICP was also reflective of other self-reported outcomes at 3 and 12 months, as most demonstrated notable improvement. Higher severity in all categories of self-reported outcomes was related to a continued HICP condition at 3 months. Both social and biological factors predicted HICP translation, with social factors being predominant in transitioning to HICP (from none preoperatively). CONCLUSIONS Many individuals who received CSM surgery changed HICP status at 3 months. In a surgical population where decisions are based on disease progression, most of the changed status went from HICP preoperatively to none at 3 months. Both social and biological risk factors predicted HICP transition assignment.