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Abstract B-cell lymphoma is a potential cause of spinal cord compression that presents with nonspecific symptoms and inconsistent imaging findings. Surgical decompression is a mainstay for both diagnosis and management especially in patients with acute neurologic deficits; however, the long-term efficacy of intervention is still unclear. We perform a systematic review of the clinical symptoms, radiographic findings, and outcome after spinal decompression in B-cell lymphoma. The databases of Medline, PubMed, and the Cochrane Database of Systemic Reviews were queried for all articles reporting spinal B-cell lymphoma. Data on presenting symptoms, histological markers, treatment and survival outcomes were extracted. Bivariate and Multivariate Cox survival regression models and Kaplan-Meier curves were generated using R software survival package. In total, 57 studies were included with 72 patients diagnosed with spinal B-cell lymphoma. Mean age was 56.22 (IQR: 45.00-70.25) with 68% of patients being male and 4.2% of patients being immunocompromised. Back pain was the most common symptom (74%) with B symptoms and cauda equina symptoms present in only 6% and 29% respectively. Mean length of symptoms before presentation was 3.81 months (IQR: 0.45-3.25). The most common location was the thoracic spine (53%), with a majority of the lesions being hyperintense (28%) on T2 MRI. Surgical resection was performed in 83% of patients. Symptoms improved in 88% of patients after surgery and 80% of patients treated nonoperatively. OS at one- and five-years was 85% (95% CI: 0.749-0.953; n=72) and 66% (95% CI: 0.512-0.847; n=72), respectively. Age > 70 was associated with poorer OS in bivariate (HR 4.07 [95% CI: 1.328-12.46], p < 0.01; n=72) and multivariate analysis (HR 3.829 [95% CI: 1.158-12.662], p < 0.03; n=72). Primary spinal B-cell lymphoma can have a variety of presentations. Both surgery and nonoperative management may have similar improvement in symptoms. Age > 70 appears to confer poorer OS.

OBJECTIVE Patients who undergo surgery for cervical spondylotic myelopathy (CSM) will occasionally develop postoperative neck pain that was not present preoperatively, yet the incidence of this phenomenon is unclear. The authors aimed to elucidate patient and surgical factors associated with new-onset sustained pain after CSM surgery. METHODS The authors reviewed data from the Quality Outcomes Database (QOD) CSM module. The presence of neck pain was defined using the neck pain numeric rating scale (NRS). Patients with no neck pain at baseline (neck NRS score ≤ 1) were then stratified based on the presence of new postoperative pain development (neck NRS score ≥ 2) at 12 and 24 months postoperatively. RESULTS Of 1141 patients in the CSM QOD, 224 (19.6%) reported no neck pain at baseline. Among 170 patients with no baseline neck pain and available 12-month follow-up, 46 (27.1%) reported new postoperative pain. Among 184 patients with no baseline neck pain and available 24-month follow-up, 53 (28.8%) reported new postoperative pain. The mean differences in neck NRS scores were 4.3 for those with new postoperative pain compared with those without at 12 months (4.4 ± 2.2 vs 0.1 ± 0.3, p < 0.001) and 3.9 at 24 months (4.1 ± 2.4 vs 0.2 ± 0.4, p < 0.001). The majority of patients reporting new-onset neck pain reported being satisfied with surgery, but their satisfaction was significantly lower compared with patients without pain at the 12-month (66.7% vs 94.3%, p < 0.001) and 24-month (65.4% vs 90.8%, p < 0.001) follow-ups. The baseline Neck Disability Index (NDI) was an independent predictor of new postoperative neck pain at both the 12-month and 24-month time points (adjusted OR [aOR] 1.04, 95% CI 1.01–1.06; p = 0.002; and aOR 1.03, 95% CI 1.01–1.05; p = 0.026, respectively). The total number of levels treated was associated with new-onset neck pain at 12 months (aOR 1.34, 95% CI 1.09–1.64; p = 0.005), and duration of symptoms more than 3 months was a predictor of 24-month neck pain (aOR 3.22, 95% CI 1.01–10.22; p = 0.048). CONCLUSIONS Increased NDI at baseline, number of levels treated surgically, and duration of symptoms longer than 3 months preoperatively correlate positively with the risk of new-onset neck pain following CSM surgery. The majority of patients with new-onset neck pain still report satisfaction from surgery, suggesting that the risk of new-onset neck pain should not hinder indicated operations from being performed.

OBJECTIVE Prior studies have revealed that a body mass index (BMI) ≥ 30 is associated with worse outcomes following surgical intervention in grade 1 lumbar spondylolisthesis. Using a machine learning approach, this study aimed to leverage the prospective Quality Outcomes Database (QOD) to identify a BMI threshold for patients undergoing surgical intervention for grade 1 lumbar spondylolisthesis and thus reliably identify optimal surgical candidates among obese patients. METHODS Patients with grade 1 lumbar spondylolisthesis and preoperative BMI ≥ 30 from the prospectively collected QOD lumbar spondylolisthesis module were included in this study. A 12-month composite outcome was generated by performing principal components analysis and k-means clustering on four validated measures of surgical outcomes in patients with spondylolisthesis. Random forests were generated to determine the most important preoperative patient characteristics in predicting the composite outcome. Recursive partitioning was used to extract a BMI threshold associated with optimal outcomes. RESULTS The average BMI was 35.7, with 282 (46.4%) of the 608 patients from the QOD data set having a BMI ≥ 30. Principal components analysis revealed that the first principal component accounted for 99.2% of the variance in the four outcome measures. Two clusters were identified corresponding to patients with suboptimal outcomes (severe back pain, increased disability, impaired quality of life, and low satisfaction) and to those with optimal outcomes. Recursive partitioning established a BMI threshold of 37.5 after pruning via cross-validation. CONCLUSIONS In this multicenter study, the authors found that a BMI ≤ 37.5 was associated with improved patient outcomes following surgical intervention. These findings may help augment predictive analytics to deliver precision medicine and improve prehabilitation strategies.

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.

Abstract Background: Associations between candidate germline genetic variants and treatment outcome of oxaliplatin, a drug commonly used for patients with colorectal cancer, have been reported but not robustly established. This study aimed to construct polygenic hazard scores (PHSs) as predictive markers for oxaliplatin treatment outcome by using a supervised principal component approach (PCA). Methods: Genome-wide association analysis for overall survival, including interaction terms (SNP*treatment type) was carried out using two phase III trials, 3,098 resected stage III colon cancer (rCC) patients of NCCTG N0147 and 506 metastatic colorectal cancer (mCRC) patients of NCCTG N9741, separately. SNPs showing interaction with genome-wide significance (P &lt; 5 × 10–8) were selected for PCA to derive a PHS. PHS interaction with treatment was included in Cox regression models to predict outcome. Replication of prediction models was performed in an independent cohort, DACHS. Results: The two PHSs based on the first two principal components of selected SNPs (15SNPs for rCC and 13SNPs for mCRC) were used to construct interaction terms with treatment type and included in models adjusted for clinical covariables. However, in the DACHS study, the addition of the two PHS terms to clinical models did not improve the prediction error in either patients with rCC or mCRC. PHS interaction was also not replicated. Conclusions: The PHSs derived using principal components efficiently combined multiple predictive SNPs for estimating likelihood of benefit from oxaliplatin versus other treatment but could not be replicated. Impact: These results highlight the potential but also challenges in generating evidence for a predictive polygenic score for oxaliplatin efficacy.

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.

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.

Abstract Background The use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk. Methods We conducted a genome-wide, gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen only, and combined estrogen-progestogen therapy with CRC risk, among 28 486 postmenopausal women (11 519 CRC patients and 16 967 participants without CRC) from 38 studies, using logistic regression, 2-step method, and 2– or 3–degree-of-freedom joint test. A set-based score test was applied for rare genetic variants. Results The use of any MHT, estrogen only and estrogen-progestogen were associated with a reduced CRC risk (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.78; OR = 0.65, 95% CI = 0.53 to 0.79; and OR = 0.73, 95% CI = 0.59 to 0.90, respectively). The 2-step method identified a statistically significant interaction between a GRIN2B variant rs117868593 and MHT use, whereby MHT-associated CRC risk was statistically significantly reduced in women with the GG genotype (OR = 0.68, 95% CI = 0.64 to 0.72) but not within strata of GC or CC genotypes. A statistically significant interaction between a DCBLD1 intronic variant at 6q22.1 (rs10782186) and MHT use was identified by the 2–degree-of-freedom joint test. The MHT-associated CRC risk was reduced with increasing number of rs10782186-C alleles, showing odds ratios of 0.78 (95% CI = 0.70 to 0.87) for TT, 0.68 (95% CI = 0.63 to 0.73) for TC, and 0.66 (95% CI = 0.60 to 0.74) for CC genotypes. In addition, 5 genes in rare variant analysis showed suggestive interactions with MHT (2-sided P &lt; 1.2 × 10−4). Conclusion Genetic variants that modify the association between MHT and CRC risk were identified, offering new insights into pathways of CRC carcinogenesis and potential mechanisms involved.

Abstract Background: Currently known associations between common genetic variants and colorectal cancer explain less than half of its heritability of 25%. As alcohol consumption has a J-shape association with colorectal cancer risk, nondrinking and heavy drinking are both risk factors for colorectal cancer. Methods: Individual-level data was pooled from the Colon Cancer Family Registry, Colorectal Transdisciplinary Study, and Genetics and Epidemiology of Colorectal Cancer Consortium to compare nondrinkers (≤1 g/day) and heavy drinkers (&gt;28 g/day) with light-to-moderate drinkers (1–28 g/day) in GxE analyses. To improve power, we implemented joint 2df and 3df tests and a novel two-step method that modifies the weighted hypothesis testing framework. We prioritized putative causal variants by predicting allelic effects using support vector machine models. Results: For nondrinking as compared with light-to-moderate drinking, the hybrid two-step approach identified 13 significant SNPs with pairwise r2 &gt; 0.9 in the 10q24.2/COX15 region. When stratified by alcohol intake, the A allele of lead SNP rs2300985 has a dose–response increase in risk of colorectal cancer as compared with the G allele in light-to-moderate drinkers [OR for GA genotype = 1.11; 95% confidence interval (CI), 1.06–1.17; OR for AA genotype = 1.22; 95% CI, 1.14–1.31], but not in nondrinkers or heavy drinkers. Among the correlated candidate SNPs in the 10q24.2/COX15 region, rs1318920 was predicted to disrupt an HNF4 transcription factor binding motif. Conclusions: Our study suggests that the association with colorectal cancer in 10q24.2/COX15 observed in genome-wide association study is strongest in nondrinkers. We also identified rs1318920 as the putative causal regulatory variant for the region. Impact: The study identifies multifaceted evidence of a possible functional effect for rs1318920.