Clinical trial links oncolytic immunoactivation to survival in glioblastoma.

Immunotherapy failures can result from the highly suppressive tumour microenvironment that characterizes aggressive forms of cancer such as recurrent glioblastoma (rGBM)1,2. Here we report the results of a first-in-human phase I trial in 41 patients with rGBM who were injected with CAN-3110-an oncolytic herpes virus (oHSV)3. In contrast to other clinical oHSVs, CAN-3110 retains the viral neurovirulence ICP34.5 gene transcribed by a nestin promoter; nestin is overexpressed in GBM and other invasive tumours, but not in the adult brain or healthy differentiated tissue4. These modifications confer CAN-3110 with preferential tumour replication. No dose-limiting toxicities were encountered. Positive HSV1 serology was significantly associated with both improved survival and clearance of CAN-3110 from injected tumours. Survival after treatment, particularly in individuals seropositive for HSV1, was significantly associated with (1) changes in tumour/PBMC T cell counts and clonal diversity, (2) peripheral expansion/contraction of specific T cell clonotypes; and (3) tumour transcriptomic signatures of immune activation. These results provide human validation that intralesional oHSV treatment enhances anticancer immune responses even in immunosuppressive tumour microenvironments, particularly in individuals with cognate serology to the injected virus. This provides a biological rationale for use of this oncolytic modality in cancers that are otherwise unresponsive to immunotherapy (ClinicalTrials.gov: NCT03152318 ).

Anterior Cervical Discectomy and Fusion Versus Cervical Disc Replacement for a Workers' Compensation Population in an Ambulatory Surgical Center.

STUDY DESIGN: Retrospective Cohort. OBJECTIVE: To evaluate patient-reported outcome measures (PROM) and minimal clinically important difference (MCID) achievement outcomes between anterior cervical discectomy and fusion (ACDF) and cervical disk replacement (CDR) in the Workers' Compensation (WC) population. SUMMARY OF BACKGROUND DATA: No studies to our knowledge have compared PROMs and MCID attainment between ACDF and CDR among patients with WC insurance undergoing surgery in an outpatient ambulatory surgical center (ASC). METHODS: WC insurance patients undergoing primary, single/double-level ACDF/CDR in an ASC were identified. Patients were divided into ACDF versus CDR. PROMs were collected at preoperative/6-week/12-week/6-month/1-year timepoints, including PROMIS-PF, SF-12 PCS/MCS, VAS neck/arm, and NDI. RESULTS: Seventy-nine patients were included, 51 ACDF/28 CDR. While operative time (56.4 vs. 54.4 min), estimated blood loss (29.2 vs. 25.9 mL), POD0 pain (4.9 vs. 3.8), and POD0 narcotic consumption (21.2 vs. 14.5 oral morphine equivalents) were higher in ACDF patients, none reached statistical significance ( P >0.050, all). One-year arthrodesis rate was 100.0% among ACDF recipients with available imaging (n=36). ACDF cohort improved from preoperative for PROMIS-PF from 12 weeks to 1 year, SF-12 PCS at 6 months, all timepoints for VAS neck/arm, and 12 weeks/6 months for NDI ( P ≤0.044, all). CDR cohort improved from preoperative for PROMIS-PF at 6 months, VAS neck/arm from 12 weeks to 1 year, and NDI at 12 weeks/6 months ( P ≤0.049, all). CDR cohort reported significantly lower VAS neck at 12 weeks/1 year and VAS arm at 12 weeks ( P ≤0.039, all). MCID achievement rates did not differ. CONCLUSION: While operative duration/estimated blood loss/acute postoperative pain/narcotic consumption were, on average, higher among ACDF recipients, these were not statistically significant, possibly due to the limited sample size. ACDF and CDR ASC patients generally demonstrated comparable arm pain/disability/physical function/mental health, though neck pain was significantly lower at multiple timepoints among CDR patients. Clinically meaningful PROM improvements were comparable. Larger, multicentered studies are required to confirm our results.

Impact of American Society of Anesthesiologists' Classification on Postoperative Satisfaction and Clinical Outcomes Following Lumbar Decompression: Cohort-Matched Analysis.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: The aim was to compare patient-reported outcomes (PROMs), minimum clinically important difference (MCID) achievement, and postoperative satisfaction following minimally invasive lumbar decompression in patients stratified by American Society of Anesthesiologists (ASA) classification. SUMMARY OF BACKGROUND DATA: Some guidelines recommend against performing elective procedures for patients with an ASA score of 3 or greater; however, long-term postoperative outcomes are not well described. METHODS: Primary, single-level, minimally invasive lumbar decompression procedures were identified. PROMs were administered at preoperative, 6-week, 12-week, 6-month, 1-year, 2-year timepoints and included Patient-Reported Outcomes Measurement Information System-Physical Function, visual analog scale (VAS) back/leg, Oswestry disability index (ODI), and 12-item short form physical component score. Satisfaction scores were collected postoperatively for VAS back/leg, ODI, and individual ODI subcategories. Patients were grouped (ASA<3, ASA≥3), and propensity scores were matched to control for significant differences. Demographic and perioperative characteristics were compared using χ 2 and the Student's t test. Mean PROMs and postoperative satisfaction were compared at each time point by a 2-sample t test. Postoperative PROM improvement from the preoperative baseline within each cohort was calculated with a paired t test. MCID achievement was determined by comparing ΔPROMs to established thresholds and comparing between groups using simple logistic regression. RESULTS: One hundred and twenty-nine propensity-matched patients were included: 99 ASA<3 and 30 ASA≥3. No significant demographic differences were observed between groups. ASA≥3 patients experienced significantly increased length of stay and postoperative narcotic consumption on surgery day ( P <0.048, all). Mean PROMs and MCID achievement did not differ. The ASA<3 cohort significantly improved from the preoperative baseline for all PROMs at all postoperative time points. ASA<3 patients demonstrated higher levels of postoperative satisfaction at 6 weeks for VAS leg, VAS back, ODI, sleeping, lifting, walking, standing, sex, travel, and at 6 months for VAS back ( P <0.045, all). CONCLUSION: ASA≥3 patients may achieve similar long-term clinical outcomes to ASA<3 patients, though they may show poorer short-term satisfaction for disability, leg pain, and back pain, which could be related to differing preoperative expectations.

Usage Trends and Safety Profile of Recombinant Human Bone Morphogenetic Protein-2 for Spinal Column Tumor Surgery: A National Matched Cohort Analysis.

STUDY DESIGN: Retrospective Cohort Analysis. OBJECTIVE: The purpose of this study is to investigate national rates of rhBMP-2 utilization in spinal tumor surgery and examine its association with postoperative complications, revisions, and carcinogenicity. METHODS: All patients diagnosed with primary or metastatic spinal tumors with subsequent surgical intervention involving a spinal fusion procedure were identified in PearlDiver. Patients were 1:1 matched into 2 cohorts according to rhBMP-2 usage. Postoperative complications and revisions were examined at 1 month, 3 months, 6 months, and 1 year after fusion. New cancer incidence following spinal tumor surgery was assessed until 5 years postoperatively. RESULTS: A total of 11,198 patients underwent fusion surgery after resection of spinal tumors between 2005 and 2020, with 909 cases reporting the use of rhBMP-2 (8.1%). An annualized analysis revealed that the proportion of spine tumor fusion procedures utilizing rhBMP-2 has been significantly decreasing (R2 = .859, P < .001), with the most recent annual utilization rate at 1.1%. At least 3 months after surgery, significantly increased incidences of surgical site (11.4% vs 3.3%, P = .03) and systemic infections (8.1% vs 1.6%, P = .02) were observed in patients who underwent fusion with rhBMP-2. Across all time points, no significant differences were observed in survival, implant removal, revision rates, or new cancer diagnoses. CONCLUSION: This analysis demonstrated significantly declining national utilization rates. Spinal tumor cases utilizing rhBMP-2 sustained greater rates of surgical site and systemic infections. rhBMP-2 usage did not significantly reduce the risk of mortality, implant failure, or reoperation.

The Influence of Presenting Physical Function on Postoperative Patient Satisfaction and Clinical Outcomes Following Minimally Invasive Lumbar Decompression.

STUDY DESIGN: The study of retrospective cohort. OBJECTIVE: The aim was to compare patient-reported outcome measures (PROMs), satisfaction, and minimum clinically important difference (MCID) achievement following minimally invasive lumbar decompression (MIS-LD) in patients stratified by the preoperative patient-reported outcomes measurement information system physical function (PROMIS-PF) score. SUMMARY OF BACKGROUND DATA: Although prior studies have assessed the predictive utility of preoperative PROMIS-PF scores on patient outcomes in spinal fusion, its utility has not been studied for patients undergoing MIS-LD. METHODS: Primary, single/multilevel MIS-LD procedures were identified. PROMs were administered at preoperative/6-week/12-week/6-month/1-year/2-year time points and included PROMIS-PF/visual analog scale (VAS) back and leg/Oswestry Disability Index (ODI). Satisfaction scores were collected postoperatively. The patients were grouped by preoperative PROMIS-PF score (≤35, >35), with higher scores indicating improved physical function. Demographic/perioperative characteristics were compared using χ 2 /Student t test. Mean PROMs/postoperative satisfaction was compared utilizing 2-sample t test. Postoperative PROM improvement from preoperative was calculated with paired t tests. MCID achievement rates were compared using simple logistic regression. RESULTS: Two hundred and sixteen patients were included, 58 PROMIS-PF≤35 and 158 PROMIS-PF>35. Ethnicity/insurance differed ( P ≤0.004, all). Hospital length of stay was greater for PROMIS-PF>35 ( P =0.042). All preoperative mean PROMs significantly differed except for VAS Back. Several postoperative mean PROMs differed: PROMIS-PF at 6 weeks/12 weeks/6 months/1 year, SF-12 PCS at 6 weeks/12 weeks/1 year, VAS Back at 6 weeks/12 weeks, VAS leg at 6 weeks/12 weeks, and ODI at 6 weeks/12 weeks ( P <0.050, all). All PROMs significantly improved from preoperative at all postoperative time points ( P <0.003, all). The MCID achievement rates differed only for VAS back for 6 weeks, favoring PROMIS-PF>35 cohort ( P =0.001). Postoperative satisfaction was greater in PROMIS-PF>35 cohort for VAS leg at 6 weeks/12 weeks/6 months/2 years, VAS back at 6-weeks/12-weeks, and ODI at all time points ( P <0.037, all). Postoperative satisfaction was greater in PROMIS-PF>35 cohort for individual ODI categories: sleep at 6-weeks/12-weeks/1-year/2-years, lifting, walking, standing, and travel at all time points, and sexual at 6-weeks/12-weeks/1-year/2-years ( P <0.030, all). CONCLUSION: Poorer preoperative PROMIS-PF scores were associated with worse postoperative clinical outcomes and satisfaction. By stratifying patients with preoperative PROMIS-PF scores, surgeons may better predict postoperative clinical improvement and seek to manage patient expectations.

Impact of Postoperative Length of Stay on Patient-Reported and Clinical Outcomes After Anterior Lumbar Interbody Fusion.

BACKGROUND: Existing literature has not yet evaluated the impact of postoperative length of stay (LOS) on patient-reported outcome measures (PROMs) and minimum clinically important difference (MCID) in patients undergoing anterior lumbar interbody fusion (ALIF). The authors investigates the influence of postoperative LOS following ALIF on PROMs and MCID achievement rates. METHODS: A single-surgeon database was retrospectively reviewed for patients undergoing single-level ALIF. The following 2 cohorts were studied: patients with LOS <45 hours and patients with LOS ≥45 hours. The following PROMs were recorded at preoperative and 6-week, 12-week, 6-month, 1-year, and 2-year postoperative timepoints: visual analog scale (VAS) back and leg, Oswestry Disability Index (ODI), 12-item short form (SF-12) physical composite score (PCS), and patient-reported outcome measurement information system physical function. MCID achievement was compared by LOS grouping using χ 2 analysis. The rates of complications by LOS grouping and the relative risk among demographic and perioperative characteristics for a longer hospital stay of ≥45 hours were calculated. RESULTS: A total of 52 subjects were included in each cohort. LOS ≥45 hours demonstrated worse ODI at 6 weeks and SF-12 PCS preoperative and at 12 weeks (P ≤ 0.026, all). LOS <45 hours demonstrated greater MCID rates for all PROMs except VAS back (P ≤ 0.004, all). Postoperative urinary retention (POUR), fever, and total complications (P ≤ 0.003, all) were associated with increased LOS. Diabetes (P = 0.037), preoperative VAS neck ≥7 (P = 0.012), and American Society of Anesthesiologists classification ≥2 (P = 0.003) served as preoperative risk factors for postoperative stay ≥45 hours. CONCLUSION: Following single-level ALIF, patients with shorter LOS demonstrated significantly greater overall MCID achievement for most PROMs. POUR, fever, and total complications were associated with longer LOS and greater blood loss. Diabetes and higher preoperative leg pain were identified as risk factors for longer LOS. CLINICAL RELEVANCE: Patients undergoing ALIF with shorter LOS had greater MCID achievement for disability, physical function, and leg pain outcomes. Patients with greater preoperative leg pain and diabetes may be at risk for longer LOS.

Does Baseline Severity of Arm Pain Influence Outcomes Following Single-Level Anterior Cervical Discectomy and Fusion?

STUDY DESIGN: Retrospective cohort. PURPOSE: To assess preoperative arm pain severity influence on postoperative patient-reported outcomes measures (PROMs) and minimal clinically important difference (MCID) achievement following single-level anterior cervical discectomy and fusion (ACDF). OVERVIEW OF LITERATURE: There is evidence that preoperative symptom severity can affect postoperative outcomes. Few have evaluated this association between preoperative arm pain severity and postoperative PROMs and MCID achievement following ACDF. METHODS: Individuals undergoing single-level ACDF were identified. Patients were grouped by preoperative Visual Analog Scale (VAS) arm ≤8 vs. >8. PROMs collected preoperatively and postoperatively included VAS-arm/VAS-neck/Neck Disability Index (NDI)/12-item Short Form (SF-12) Physical Composite Score (PCS)/SF-12 mental composite score (MCS)/Patient-Reported Outcomes Measurement Information System physical function (PROMIS-PF). Demographics, PROMs, and MCID rates were compared between cohorts. RESULTS: A total of 128 patients were included. The VAS arm ≤8 cohort significantly improved for all PROMs excepting VAS arm at 1-year/2-years, SF-12 MCS at 12-weeks/1-year/2-years, and SF-12 PCS/PROMIS-PF at 6-weeks, only (p ≤0.021, all). The VAS arm >8 cohort significantly improved for VAS neck at all timepoints, VAS arm from 6-weeks to 1-year, NDI from 6-weeks to 6-months, and SF-12 MCS/PROMIS-PF at 6-months (p ≤0.038, all). Postoperatively, the VAS arm >8 cohort had higher VAS-neck (6 weeks/6 months), VAS-arm (12 weeks/6 months), NDI (6 weeks/6 months), lower SF-12 MCS (6 weeks/6 months), SF-12 PCS (6 months), and PROMISPF (12 weeks/6 months) (p ≤0.038, all). MCID achievement rates were higher among the VAS arm >8 cohort for the VAS-arm at 6-weeks/12-weeks/1-year/overall and NDI at 2 years (p ≤0.038, all). CONCLUSIONS: Significance in PROM score differences between VAS arm ≤8 vs. >8 generally dissipated at the 1-year and 2-year timepoint, although higher preoperative arm pain patients suffered from worse pain, disability, and mental/physical function scores. Furthermore, clinically meaningful rates of improvement were similar throughout the vast majority of timepoints for all PROMs studied.

Does Baseline Mental Health Influence Outcomes among Workers' Compensation Claimants Undergoing Minimally Invasive Transforaminal Lumbar Interbody Fusion?

STUDY DESIGN: This was a retrospective cohort study. PURPOSE: This study investigated the influence of preoperative mental health on patient-reported outcome measures (PROMs) and minimal clinically important difference (MCID) among workers' compensation (WC) recipients undergoing minimally invasive transforaminal lumbar interbody fusion (MIS TLIF). OVERVIEW OF LITERATURE: No studies have evaluated the impact of preoperative mental functioning on outcomes following MIS TLIF among WC claimants. METHODS: WC recipients undergoing single-level MIS TLIF were identified. PROMs of Visual Analog Scale (VAS) for back and leg pain, Oswestry Disability Index (ODI), 12-item Short Form Physical and Mental Composite Scale (SF-12 PCS/MCS), and Patient-Reported Outcomes Measurement Information System Physical Function evaluated subjects preoperatively/postoperatively. Subjects were grouped according to preoperative SF-12 MCS: <41 vs. ≥41. Demographic/perioperative variables, PROMs, and MCID were compared using inferential statistics. Multiple regression was used to account for differences in spinal pathology. RESULTS: The SF-12 MCS <41 and SF-12 MCS ≥41 groups included 48 and 45 patients, respectively. Significant differences in ΔPROMs were observed at SF-12 MCS at all timepoints, except at 6 months (p≤0.041, all). The SF-12 MCS <41 group had worse preoperative to 6-months SF-12 MCS, 12-weeks/6-months VAS back, 12-week VAS leg, and preoperative to 6-months ODI (p≤0.029, all). The SF-12 MCS <41 group had greater MCID achievement for overall ODI and 6-weeks/1-year/overall SF-12 MCS (p≤0.043, all); the SF-12 MCS ≥41 group had greater attainment for 6-month VAS back (p=0.004). CONCLUSIONS: Poorer mental functioning adversely affected the baseline and intermediate postoperative quality-of-life outcomes pertaining to mental health, back pain, and disability among WC recipients undergoing lumbar fusion. However, outcomes did not differ 1-2 years after surgery. While MCID achievement for pain and physical function was largely unaffected by preoperative mental health score, WC recipients with poorer baseline mental health demonstrated higher rates of overall clinically meaningful improvements for disability and mental health.

Single-Level Anterior Lumbar Interbody Fusion versus Minimally Invasive Transforaminal Lumbar Interbody Fusion at L5/S1 for an Obese Population.

STUDY DESIGN: Retrospective study. PURPOSE: To compare perioperative outcomes, patient-reported outcome measures (PROMs), and minimal clinically important difference (MCID) achievement rates for an obese patient cohort between single-level minimally invasive (MIS) transforaminal lumbar interbody fusion (TLIF) vs. anterior lumbar interbody fusion (ALIF). OVERVIEW OF LITERATURE: To the best of our knowledge, no study has compared the outcomes of MIS TLIF and ALIF in an obese population. METHODS: Obese patients (body mass index [BMI] ≥30.0 kg/m2) who underwent single-level MIS TLIF or ALIF at L5/S1 were included in the study. Demographic/perioperative variables, presenting patient pathology, and 1-year arthrodesis statistics were collected. PROM scores for Visual Analog Scale (VAS) back/leg, Oswestry Disability Index, 12-item Short Form Physical Composite Scale, and Patient-Reported Outcome Measurement Information System Physical Function (PROMIS-PF) were collected from preoperative and postoperative (6 weeks, 12 weeks, 6 months, 1 year, 2 years) PROMIS-PF. The obese patients were classified based on the procedure they underwent (MIS TLIF vs. ALIF). RESULTS: The criteria were met by 210 patients in total. After coarsened exact matching for Charlson comorbidity index score, degenerative spondylolisthesis, isthmic spondylolisthesis, degenerative scoliosis, foraminal stenosis, insurance, male, and ethnicity, 94 obese patients were included in the total cohort, with 59 receiving MIS TLIF and 35 receiving ALIF. ALIF recipients had higher PROMIS-PF scores at 6 weeks (p=0.014) and 12 weeks (p=0.030), as well as a higher VAS leg at 2 years (p=0.017). Following multiple regression accounting for differences in baseline BMI, only the 6-week PROMIS-PF significantly differed (p=0.028), with no other intergroup differences in mean PROMs between fusion types. Aside from a significantly higher 6-week MCID achievement rate for PROMIS-PF among ALIF recipients (p=0.006), no differences in attainment were observed. CONCLUSIONS: There were no statistically significant differences in perioperative characteristics, fusion rates, PROMs, or MCID achievement between obese patients receiving MIS TLIF vs. ALIF. As a result, our findings indicate that MIS TLIF and ALIF at L5/S1 are equally effective in an obese patient population.

The Current Status of Awake Endoscopic Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVE: To examine the use of local anesthesia and/or conscious sedation in endoscopic spine procedures within the past decade. METHODS: This systematic review abided by PRISMA guidelines. Embase, PubMed, Google Scholar, and Cochrane databases were searched for post-2011 articles with patients >18 years old, lumbar/cervical percutaneous endoscopic spine procedures using local/awake anesthesia, and patient/surgical outcomes. Reviews, book chapters, single case reports, or small case series (n ≤15 patients) were excluded. Scoring systems of the National Institutes of Health quality assessment tool, Newcastle-Ottawa Scale, and Cochrane Risk of Bias evaluated interventional case series, comparative studies, and randomized control trials, respectively. RESULTS: Twenty-six articles were included, with 4 studies comparing general and local anesthesia. Of 2113 total patients, 1873 patients received local anesthesia. Significant improvements were seen in pain and disability scores. Studies that included MacNab scores showed that 96% of patients rated their postoperative satisfaction as excellent to good. Subanalysis of comparative studies showed a reduced risk of surgical/major medical complications and a slight increased risk for minor medical complications among awake spine patients. Length of stay was shorter for patients receiving local anesthesia. CONCLUSIONS: The current systematic review and meta-analysis shows that use of local anesthesia is a safe and effective alternative to general anesthesia among different endoscopic spinal procedures. Although awake spine surgery is associated with a decreased risk of severe complications, lower revision rates, and higher postoperative satisfaction, more robust studies involving larger cohorts of patients are needed to evaluate the true impact of awake spine surgery on outcomes.

Validation of Neck Disability Index Severity among Patients Receiving One or Two-Level Anterior Cervical Surgery.

STUDY DESIGN: Retrospective cohort. PURPOSE: To evaluate the validity of established severity thresholds for Neck Disability Index (NDI) among patients undergoing anterior cervical discectomy and fusion (ACDF) or cervical disc arthroplasty (CDA). OVERVIEW OF LITERATURE: Few studies have examined the validity of established NDI threshold values among patients undergoing ACDF or CDA. METHODS: A surgical database was reviewed to identify patients undergoing cervical spine procedures. Demographics, operative characteristics, comorbidities, NDI, Visual Analog Scale (VAS), and 12-item Short Form (SF-12) physical and mental composite scores (PCS and MCS) were recorded. NDI severity was categorized using previously established threshold values. Improvement from preoperative scores at each postoperative timepoint and convergent validity of NDI was evaluated. Discriminant validity of NDI was evaluated against VAS neck and arm and SF-12 PCS and MCS. RESULTS: All 290 patients included in the study demonstrated significant improvements from baseline values for all patient-reported outcome measures (PROMs) at all postoperative timepoints (p<0.001) except SF-12 MCS at 2 years (p =0.393). NDI showed a moderate- to-strong correlation (r≥0.419) at most timepoints for VAS neck, VAS arm, SF-12 PCS, and SF-12 MCS (p<0.001, all). NDI severity categories demonstrated significant differences in mean VAS neck, VAS arm, SF-12 PCS, and SF-12 MCS at all timepoints (p<0.001, all). Differences between NDI severity groups were not uniform for all PROMs. VAS neck values demonstrated significant intergroup differences at most timepoints, whereas SF-12 MCS showed significantly different values between most severity groups. CONCLUSIONS: Neck disability is strongly correlated with neck and arm pain, physical function, and mental health and demonstrates worse outcomes with increasing severity. Previously established severity categories may be more applicable to pain than physical function or mental health and may be more uniformly applied preoperatively for cervical spine patients.

Investigative needle core biopsies for multi-omics in Glioblastoma.

Glioblastoma (GBM) is a primary brain cancer with an abysmal prognosis and few effective therapies. The ability to investigate the tumor microenvironment before and during treatment would greatly enhance both understanding of disease response and progression, as well as the delivery and impact of therapeutics. Stereotactic biopsies are a routine surgical procedure performed primarily for diagnostic histopathologic purposes. The role of investigative biopsies - tissue sampling for the purpose of understanding tumor microenvironmental responses to treatment using integrated multi-modal molecular analyses ('Multi-omics") has yet to be defined. Secondly, it is unknown whether comparatively small tissue samples from brain biopsies can yield sufficient information with such methods. Here we adapt stereotactic needle core biopsy tissue in two separate patients. In the first patient with recurrent GBM we performed highly resolved multi-omics analysis methods including single cell RNA sequencing, spatial-transcriptomics, metabolomics, proteomics, phosphoproteomics, T-cell clonotype analysis, and MHC Class I immunopeptidomics from biopsy tissue that was obtained from a single procedure. In a second patient we analyzed multi-regional core biopsies to decipher spatial and genomic variance. We also investigated the utility of stereotactic biopsies as a method for generating patient derived xenograft models in a separate patient cohort. Dataset integration across modalities showed good correspondence between spatial modalities, highlighted immune cell associated metabolic pathways and revealed poor correlation between RNA expression and the tumor MHC Class I immunopeptidome. In conclusion, stereotactic needle biopsy cores are of sufficient quality to generate multi-omics data, provide data rich insight into a patient's disease process and tumor immune microenvironment and can be of value in evaluating treatment responses. One sentence summary: Integrative multi-omics analysis of stereotactic needle core biopsies in glioblastoma.

Comparing Patient-Reported Outcomes in Patients Undergoing Lumbar Fusion for Isthmic Spondylolisthesis with Predominant Back Pain versus Predominant Leg Pain Symptoms.

OBJECTIVE: To compare patient-reported outcome measures (PROMs) and minimum clinically important difference (MCID) achievement following anterior or transforaminal lumbar interbody fusion for isthmic spondylolisthesis in patients presenting with predominant back pain versus predominant leg pain symptoms. METHODS: A single-surgeon database was reviewed for anterior or transforaminal lumbar interbody fusion procedures for isthmic spondylolisthesis. Patient demographics, perioperative characteristics, postoperative complications, and PROMs were collected. Demographic/perioperative characteristics were compared among groups using χ2 and Student t tests for categorical and continuous variables, respectively. Mean PROM scores were compared using an unpaired Student t test. Postoperative improvement from preoperative baseline within each cohort was assessed with paired-samples t test. MCID achievement rates were compared with χ2 analysis. RESULTS: In total, 143 patients were included with 65 patients in the predominant back pain and 78 patients in the predominant leg pain cohort. Preoperative visual analog scale (VAS) leg was noted to be significantly greater in predominant leg pain cohort (P < 0.001). Cohorts demonstrated significant mean postoperative differences for the following PROMs at the following postoperative time points: significant differences were noted between cohorts for rate of achievement of MCID for the following PROMs at the following time points: VAS back at 2 years and VAS leg at 6 weeks/12 weeks/6 months/overall (P < 0.036, all). CONCLUSIONS: Compared with patients presenting for surgery with predominant leg pain symptoms, patients undergoing lumbar fusion at L4-L5 and L5-S1 for isthmic spondylolisthesis with predominant back pain symptoms may demonstrate improved long-term clinical outcomes for reported back pain, leg pain, and disability and reduced postoperative length of stay and narcotic consumption.

History and Evolution of the Minimally Invasive Transforaminal Lumbar Interbody Fusion.

The minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is a popular surgical technique for lumbar arthrodesis, widely considered to hold great efficacy while conferring an impressive safety profile through the minimization of soft tissue damage. This elegant approach to lumbar stabilization is the byproduct of several innovations throughout the past century. In 1934, Mixter and Barr's paper in the New England Journal of Medicine elucidated the role of disc herniation in spinal instability and radiculopathy, prompting surgeons to explore new approaches and instruments to access the disc space. In 1944, Briggs and Milligan published their novel technique, the posterior lumbar interbody fusion (PLIF), involving continuous removal of vertebral bone chips and replacement of the disc with a round bone peg. The following decades witnessed several PLIF modifications, including the addition of long pedicle screws. In 1982, Harms and Rolinger sought to redefine the posterior corridor by approaching the disc space through the intervertebral foramen, establishing the transforaminal lumbar interbody fusion (TLIF). In the 1990s, lumbar spine surgery experienced a paradigm shift, with surgeons placing increased emphasis on tissuesparing minimally invasive techniques. Spurred by this revolution, Foley and Lefkowitz published the novel MIS-TLIF technique in 2002. The MIS-TLIF has demonstrated comparable surgical outcomes to the TLIF, with an improved safety profile. Here, we present a view into the history of the posterior-approach treatment of the discogenic radiculopathy, culminating in the MIS-TLIF. Additionally, we evaluate the hallmark characteristics, technical variability, and reported outcomes of the modern MIS-TLIF and take a brief look at technologies that may define the future MIS-TLIF.

Single-level Minimally Invasive Transforaminal Lumbar Interbody Fusion Versus Anterior Lumbar Interbody Fusion for the Surgical Treatment of Isthmic Spondylolisthesis.

INTRODUCTION: Limited studies have compared minimally invasive transforaminal lumbar interbody fusion (MIS TLIF) with anterior lumbar interbody fusion (ALIF) for the treatment of isthmic spondylolisthesis. This study aims to compare perioperative variables, patient-reported outcome measures (PROMs), and minimal clinically important difference (MCID) achievement rates between these surgical approaches. METHODS: Patients with isthmic spondylolisthesis undergoing primary, single-level MIS TLIF or ALIF were identified in a surgical database. Patients were divided into MIS TLIF and ALIF cohorts. Demographics and perioperative characteristics were collected and compared between groups using the chi square test or Student t-test. PROMs including the Patient-Reported Outcomes Measurement Information System Physical Function, 12-Item Short Form Physical Composite Score, visual analog scale (VAS) back, VAS leg, and Oswestry Disability Index were collected at preoperative, 6-, 12-week, 6-month, 1-, and 2-year time points. Mean PROMs were compared using the Student t-test for independent samples. MCID attainment was determined using established values in the literature; achievement rates by grouping were compared using chi square analysis. RESULTS: One hundred seventy-one patients were included, 121 MIS TLIF and 50 ALIF. No demographic differences were observed. Mean surgical times were 139.7 minutes (MIS TLIF) and 165.5 minutes (ALIF) (P < 0.001). No other perioperative differences were observed. Mean estimated blood loss values were 63.8 mL (MIS TLIF) and 73.7 mL (ALIF). Mean postoperative lengths of stay were 43.9 hours (MIS TLIF) and 42.5 hours (ALIF). Mean PROMs did not markedly differ among groups at any time point. MCID attainment was markedly higher among MIS TLIF patients for the Oswestry Disability Index at 6 weeks (P = 0.046) and 12 weeks (P = 0.007), Patient-Reported Outcomes Measurement Information System Physical Function at 12 weeks (P = 0.015), and VAS leg at 6 weeks (P = 0.031) and 12 weeks (P = 0.045). No other notable differences were observed among MCID achievement by grouping. DISCUSSION: While single-level ALIF demonstrated markedly higher surgical times, other perioperative characteristics and PROMs were comparable among ALIF and MIS TLIF patients. Although MCID achievement rates were generally lower for disability and leg pain among ALIF patients, significance was not reached at 6 months, 1 year, or during the overall postoperative period after fusion.

Impact of age within younger populations on outcomes following cervical surgery in the ambulatory setting.

Objective: To determine the effect of age within the younger population seen at ambulatory surgical centers on patient-reported outcome measures (PROMs) after cervical spine surgery. Methods: Patients of age <65 years undergoing single-level anterior cervical discectomy and fusion (ACDF) or cervical disc replacement (CDR) were included. Patients were divided by mean age of initial population (46 years). PROMs included Patient-reported Outcome Measurement Information System Physical Function (PROMIS-PF), 12-Item Short-Form Physical Component Survey (SF-12 PCS), Visual Analog Scale (VAS) neck, VAS arm, Neck Disability Index (NDI) collected preoperatively and at postoperative time points up to 2 years. Results: 138 patients were included, with 66 patients <46 years. Both cohorts demonstrated improvement from preoperative baseline with regard to all studied PROMs at multiple time points postoperatively (p ≤ 0.042, all). Between groups, the older cohort demonstrated greater mean PROMIS-PF scores preoperatively and at 6 weeks (p ≤ 0.011, both), while VAS arm scores were lower in the older group at 1 year (p = 0.002), and NDI scores were lower in the older group at 6 weeks and 1 year (p < 0.027, both). Minimal Clinically Important Difference (MCID) achievement rates were greater in the younger group in PROMIS PF at 2 years (p = 0.002), and in the older group in VAS arm score at 1 year (p = 0.007). Conclusion: Both cohorts showed significant improvement at multiple postoperative time points for all PROMs. Between groups, the older group reported more favorable physical function, VAS arm, and NDI scores at several time points. However, MCID achievement rates only significantly differed in two PROMs at singular time points. Difference in age in patients <65 years likely does not significantly affect long-term outcomes after cervical spine surgery.

Single-Level Minimally Invasive Transforaminal Lumbar Interbody Fusion versus Anterior Lumbar Interbody Fusion with Posterior Instrumentation at L5/S1.

OBJECTIVE: To compare outcomes between minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and anterior lumbar interbody fusion (ALIF) at L5/S1. METHODS: Primary, elective, single, MIS-TLIF, or ALIF with posterior fixation at L5/S1 were identified. Patient-reported outcome measures (PROMs) were collected. Coarsened exact matching was used to control for significant differences. Achievement of minimum clinically important difference [MCID] was determined by comparing ΔPROM scores with threshold values. Demographic/perioperative characteristics were compared between MIS-TLIF and ALIF cohorts using χ2 Student t tests. Differences in mean PROM scores, MCID rates, and postoperative complications were evaluated using an unpaired t test. RESULTS: After coarsened exact matching, 93 patients received MIS-TLIF and 50 received ALIF. Cohorts differed in operative time, estimated blood loss, and postoperative narcotic consumption on postoperative day 0 (P < 0.034, all). Mean PROMs differed significantly on 12-Item Short-Form Physical Component Summary at 6 weeks and 1 year, Patient-Reported Outcomes Measurement Information System Physical Function at 6 weeks, Oswestry Disability Index at 6 weeks, and visual analog scale (VAS) back at 6 weeks, with the ALIF cohort showing significantly improved mean PROMs (P ≤ 0.044, all). Significantly greater rates were reported of MCID achievement for PROMs for the ALIF cohort: VAS back at 6 weeks, Oswestry Disability Index at 12 weeks, 12-Item Short-Form Physical Component Summary at 6 weeks, and Patient-Reported Outcomes Measurement Information System Physical Function at 12 weeks (P ≤ 0.047, all). A greater rate of MCID achievement for the MIS-TLIF cohort was seen for 6-week and overall VAS leg (P < 0.046, all). Postoperative fever was greater in the TLIF cohort (9.6% vs. 2.0%; P < 0.047). CONCLUSIONS: Patients undergoing ALIF showed significantly improved rates of MCID achievement for disability, physical function, and back pain during the early postoperative period. However, the overall MCID achievement rate for leg pain was higher for the MIS-TLIF cohort.

The Effect of the Preoperative Severity of Neck Pain on Patient-Reported Outcome Measures and Minimum Clinically Important Difference Achievement After Anterior Cervical Discectomy and Fusion.

OBJECTIVE: To compare patient-reported outcome measure (PROM) scores and minimum clinically important difference (MCID) achievement rates among patients undergoing single-level anterior cervical discectomy and fusion (ACDF) in patients with varying severity of preoperative visual analog scale (VAS) neck score. METHODS: Patients with ACDF were grouped: severity of preoperative VAS neck score ≤8 or >8. Demographic/perioperative variables and PROMs (Patient-Reported Outcomes Measurement Information System Physical Function [PROMIS PF] score, 12-Item Short Form [SF-12] Mental Component Score [MCS], VAS neck/arm score, and Neck Disability Index [NDI]) were collected preoperatively/postoperatively. MCID attainment comparison by grouping was evaluated using χ2 analysis. RESULTS: A total of 137 patients were included (103 VAS neck preoperative score ≤8; 34 VAS neck preoperative score >8). The VAS neck preoperative score ≤8 cohort did not improve: 6 weeks PROMIS-PF score, 6 weeks SF-12 Physical Component Score [PCS], 12 weeks/1 year/2 years SF-12 MCS, 2 years VAS neck score, and 1 years/2 years VAS arm score (P ≤ 0.015, all). VAS neck preoperative score >8 did not improve: 6 weeks/12 weeks/2 years PROMIS-PF score, all time points SF-12 PCS, 6 weeks/12 weeks/1 year/2 years SF-12 MCS, and 2 years VAS arm score (P ≤ 0.013, all). VAS neck preoperative score >8 had inferior PROMIS-PF scores all time points except 1 year (P ≤ 0.036, all), lower SF-12 PCS 6 weeks/6 months (P ≤ 0.043, both), inferior SF-12 MCS at preoperative to 6 months (P ≤ 006, all), higher VAS neck score from preoperative to 6 months (P ≤ 0.018), higher VAS arm score preoperative/12 weeks/6 months (P ≤ 0.020, all), and higher NDI at preoperative/12 weeks/6 months (P ≤ 0.030, all). MCID attainment rates for VAS neck preoperative score >8 were greater for NDI 2 years (P = 0.040), lower for PROMIS-PF score 2 years, and overall (P = 0.018), lower for SF-12 MCS 12 weeks (P = 0.046), lower for VAS neck score 12 weeks to 1 year and overall (P ≤ 0.032, all), and lower for VAS arm score 6 weeks/1 year (P ≤ 0.030, both). CONCLUSIONS: Patients with single-level ACDF presenting with greater baseline neck pain showed poorer physical function/pain/disability/mental health at preoperative/intermediate postoperative time points, but had comparable long-term PROMs by 2 years. MCID attainment was lower among patients with greater preoperative neck pain; MCID among the VAS neck score >8 cohort were only significantly inferior for neck pain.

Obesity and Workers' Compensation in the Setting of Minimally Invasive Lumbar Decompression.

OBJECTIVE: To investigate the influence of body mass index (BMI) on perioperative outcomes, postoperative patient-reported outcome measures (PROMs), and minimal clinically important difference (MCID) achievement among workers' compensation (WC) claimants undergoing minimally invasive lumbar decompression (MIS-LD). METHODS: WC patients diagnosed with herniated nucleus pulposus undergoing single-level MIS-LD were identified. Patients were divided into 3 groups: Non-obese (<30 kg/m2), Obese I (≥30 and <35 kg/m2), and Obese II/III (≥35 kg/m2). PROMs were collected preoperatively and at 6 weeks, 12 weeks, 6 months, 1 year, and 2 years postoperatively. The predictive influence of BMI grouping on mean PROM scores was computed using simple linear regression. To compare PROMs between groups, post hoc pairwise comparisons of adjusted means were utilized. MCID achievement was compared between groups with χ2 analysis. RESULTS: A total of 81 patients were in the Non-obese cohort, and 43 and 45 in the Obese I and Obese II/III cohorts, respectively. Visual analog scale (VAS) leg, Oswestry Disability Index (ODI), and 12-Item Short Form Physical Composite Score (SF-12 PCS) were worse in the Obese I cohort at 12 weeks, and SF-12 PCS was lower in the Obese I vs. Obese II/III subgroup analysis (P ≤ 0.045, all). MCID achievement rates for ODI were higher for the Non-obese group at 12 weeks and overall (P ≤ 0.049, both). MCID attainment for VAS back was higher among the Non-obese cohort at 6-weeks (P = 0.022). CONCLUSIONS: Patients with higher levels of obesity were more likely to experience longer length of stay and delayed discharge following MIS-LD. Increasing BMI was generally not a significant predictor of postoperative pain, disability, or physical health PROMs at most timepoints. MCID achievement rates for disability relief were significantly higher for non-obese patients.