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Selective fusion of thoracic and thoracolumbar/lumbar curves in adolescent idiopathic scoliosis is a concept critically debated in the literature. While some surgeons strongly believe that a more rigid and straighter spine provides predictably excellent outcomes, some surgeons recommend a mobile and less straight spine. This topic is a crucial part of surgical treatment of idiopathic scoliosis, particularly in young patients who will deal with the stress of the fusion mass at the proximal and distal junctions over many years. This study will review the literature on various aspects of selective fusion. [ABSTRACT FROM AUTHOR]

Background: Unilateral biportal endoscopic (UBE) microdiscectomy is an emerging minimally invasive surgery technique for treating symptomatic lumbar disc herniation. There is limited literature regarding outcomes. Here, we assess surgical outcomes and pain medication consumption for UBE vs. tubular lumbar microdiscectomy., Methods: This was a retrospective cohort study of adult patients undergoing primary, single-level UBE or tubular lumbar microdiscectomy surgery at a high-volume institution between 2018 and 2023. Variables of interest included operative time, complications and reoperations, as well as postoperative opioid and nonopioid pain medication consumption from discharge to 6 months. Opioid consumption was converted to morphine milligram equivalents. Standard statistical analyses were performed for comparative analyses., Results: One hundred two patients-48 UBE and 54 tubular-were included. Average operative time (minutes) was higher for UBE patients (133.1 UBE vs. 86.6 tubular, P < 0.001), which trended downward over time but did not reach statistical significance (P = 0.07). There were no differences in complication or reoperation rates. Average daily MME was lower from discharge to 2-week follow-up in the UBE group (11.1 v. 14.1, P = 0.02), but were comparative thereafter. Nonopioid medication prescription was lower in the UBE cohort from discharge to 2 weeks (70.8% vs. 92.6%, P = 0.01) and 2 to 6 weeks (52.1% vs. 85.2%, P < 0.001), with no significant differences thereafter., Conclusions: UBE microdiscectomy is associated with longer operating times. Both opioid and nonopioid pain medication consumption were lower for UBE patients during the initial postoperative period, perhaps owing to the less-invasive nature of the surgery., (Copyright © 2024 Elsevier Inc. All rights reserved.)

In response to the national opioid crisis, there have been increasing efforts to decrease opioid usage in favor of nonopioid alternatives. We compared post-discharge opioid and nonopioid pain medication prescriptions in lumbar microdiscectomy (MLD) patients before and after implementation of an opioid-sparing pathway for outpatient spine surgery. Patients were grouped into pre-implementation (pre) and post-implementation (post) cohorts based on date of surgery relative to pathway implementation on September 1, 2018. Primary outcomes were the average daily morphine milligram equivalent (MME) of opioids and percentages of nonopioids prescribed at 2-week, 6-week, and 3-month follow-up. Two hundred consecutive MLD patients (100 pre, 100 post) were evaluated. Pre-implementation, average daily MME significantly decreased from 19.59 at 2 weeks, to 1.73 at 6 weeks, to 0.11 at 3 months postoperatively (p < 0.001); post-implementation, average daily MME was 14.12, 1.31, and 0.27, respectively (p < 0.001). Average daily MME at 2-week follow-up decreased by 5.48 (p < 0.001) following implementation, while the rate of nonopioid prescriptions increased from 59% to 79% (p = 0.002) overall, specifically for acetaminophen (8% vs. 47%, p < 0.001) and nonsteroidal anti-inflammatory drugs (36% vs. 61%, p < 0.001). There were no significant differences at 6-week and 3-month follow-up. Opioid usage decreased while nonopioid pain medication usage increased from discharge to 2 weeks postoperatively. Beyond 2 weeks, opioid usage decreased significantly but were comparable between pre-implementation and post-implementation.

Though the United States population has rapidly diversified in recent decades, the American physician workforce has been slow to follow. Orthopedic surgery and neurosurgery are 2 specialties which remain particularly homogenous, and the subset of orthopedic surgeons and neurosurgeons who pursue spine surgery is even less diverse, along many different demographic axes. To provide effective, innovative, and accessible care to the changing population, greater diversity in spine surgery is essential. This is achieved in part by recruitment, retention, and leadership sponsorship of a new generation of trainees and faculty who reflect the diversity of the patient population they will care for. For surgeons, workforce diversity means improved learning, innovation, and organizational performance. For patients, it means greater ability to access respectful, quality care. Investing in the future of spine surgery means creating a more diverse and inclusive field, 1 in which patients from all walks of life can say, "My doctor is different-like me.", Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background Current research is limited in exploring the impact of social determinants of health (SDOH) on the discharge location within elective spine surgery. Further understanding of the influence of SDOH on disposition is necessary to improve outcomes. This study explores how SDOH influence discharge disposition for patients undergoing one- or two-level posterior interbody fusion (TLIF/PLIF). Methods This was a retrospective propensity-matched cohort study . Patients who underwent TLIF/PLIF between 2017 and 2020 at a single academic medical center were identified. The chart review gathered demographics, perioperative characteristics, intra/post-operative complications, discharge disposition, and 90-day outcomes. Discharge dispositions included subacute nursing facility (SNF), home with self-care (HSC), home with health services (HHS), and acute rehab facility (ARF). Demographic, perioperative, and disposition outcomes were analyzed by chi-square analysis and one-way ANOVA based on gender, race, and income quartiles. Results Propensity score matching for significant demographic factors isolated 326 patients. The rate of discharge to SNF was higher in females compared to males (25.00% vs 10.56%; p=0.001). Men were discharged to home at a higher rate than women (75.4% vs 61.95%; p=0.010). LatinX patients had the highest rate of home discharge, followed by Asians, Caucasians, and African Americans (83.33% vs 70.31% vs 66.45% vs 65.90%; p<0.001). The post hoc Tukey test demonstrated statistically significant differences between Asians and all other races in the context of age and BMI. Additionally, patients discharged to SNF showed the highest Charlson comorbidity index (CCI) score, followed by those at ARF, HHS, and HSC (4.36 vs 4.05 vs 2.87 vs 2.37; p<0.001). The estimated median income for the cohort ranged from $52,000 to $250,001, with no significant differences in income seen across comparisons. Conclusion Discharge disposition following one- or two-level TLIF/PLIF shows significant association with gender and race. No association was seen when comparing discharge rates among zip code-level median income quartiles., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2024, Zabat et al.)

Study Design: Single-center retrospective cohort study., Objectives: To evaluate inpatient MME administration associated with different lumbar spinal fusion surgeries., Methods: Patients ≥18 years of age with a diagnosis of Grade I or II spondylolisthesis, stenosis, degenerative disc disease or pars defect who underwent one-level Transforaminal Lumbar Interbody Fusion (TLIF) or one-level Anterior Lumbar Interbody Fusion (ALIF) or Lateral Lumbar Interbody Fusion (LLIF) through traditional MIS, anterior-posterior position or single position approaches between L2-S1. Outcome measures included patient demographics, surgical procedure and approach, perioperative clinical characteristics, incidence of ileus and inpatient MME. Statistical analysis included one-way ANOVA with a post-hoc Tukey Test and Kruskal-Wallis Test with post-hoc Mann-Whitney test. MME was calculated as per the Centers for Medicare and Medicaid Services and previous literature. Significance set at P < .05., Results: Mean age differed significantly between MIS TLIF (55.6 ± 12.5 years) and all other groups (Open TLIF 57.1 ± 12.5, SP ALIF/LLIF 57.9 ± 9.9, TP ALIF/LLIF 50.9 ± 12.7, Open ALIF/LLIF 58.4 ± 15.5). MIS TLIF had the shortest LOS compared to all groups except SP ALIF/LLIF. Total MME was significantly different between MIS TLIF and Open ALIF/LLIF (172.5 MME vs 261.1 MME, P = .044) as well as MIS TLIF and TP ALIF/LLIF (172.5 MME vs 245.4 MME, P = .009). There were no significant differences in MME/hour and incidence of ileus between all groups., Conclusion: Patients undergoing MIS TLIF had lower inpatient opioid intake compared to TP and SP ALIF/LLIF, as well as shorter LOS compared to all groups except SP ALIF/LLIF. Thus, it appears that the advantages of minimally invasive surgery are seen in minimally invasive TLIFs.

Study Design: Retrospective analysis of prospectively collected data., Objective: To investigate the effect of the approach of the transforaminal lumbar interbody fusion [TLIF; open vs . minimally invasive (MIS)] on reoperation rates due to ASD at 2 to 4-year follow-up., Summary of Background Data: Adjacent segment degeneration is a complication of lumbar fusion surgery, which may progress to adjacent segment disease (ASD) and cause debilitating postoperative pain potentially requiring additional operative management for relief. MIS TLIF surgery has been introduced to minimize this complication but the impact on ASD incidence is unclear., Materials and Methods: For a cohort of patients undergoing 1 or 2-level primary TLIF between 2013 and 2019, patient demographics and follow-up outcomes were collected and compared among patients who underwent open versus MIS TLIF using the Mann-Whitney U test, Fischer exact test, and binary logistic regression., Results: Two hundred thirty-eight patients met the inclusion criteria. There was a significant difference in revision rates due to ASD between MIS and open TLIFs at 2 (5.8% vs . 15.4%, P =0.021) and 3 (8% vs . 23.2%, P =0.03) year follow-up, with open TLIFs demonstrating significantly higher revision rates. The surgical approach was the only independent predictor of reoperation rates at both 2 and 3-year follow-ups (2 yr, P =0.009; 3 yr, P =0.011)., Conclusions: Open TLIF was found to have a significantly higher rate of reoperation due to ASD compared with the MIS approach. In addition, the surgical approach (MIS vs . open) seems to be an independent predictor of reoperation rates., Competing Interests: T.S.P. has received consulting fees from Globus Medical, Medicrea, Medtronic, Nuvasive, and Stryker, and holds stock or stock options in Spine Align and Torus Medical. C.R.F. has received consulting fees from Stryker/K2M, Globus, Zimmer-Biomet, Amplify, and Life-Spine. The remaining authors report no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Complex surgery for adult spinal deformity has high rates of complications, reoperations, and readmissions. Preoperative discussions of high-risk operative spine patients at a multidisciplinary conference may contribute to decreased rates of these adverse outcomes through appropriate patient selection and surgical plan optimization. With this goal, we implemented a high-risk case conference involving orthopedic and neurosurgery spine, anesthesia, intraoperative monitoring neurology, and neurological intensive care., Methods: Included in this retrospective review were patients ≥ 18 years old meeting one of the following high-risk criteria: 8 + levels fused, osteoporosis with 4 + levels fused, three column osteotomy, anterior revision of the same lumbar level, or planned significant correction for severe myelopathy, scoliosis (> 75˚), or kyphosis (> 75˚). Patients were categorized as Before Conference (BC): surgery before 2/19/2019 or After Conference (AC): surgery after 2/19/2019. Outcome measures include intraoperative and postoperative complications, readmissions, and reoperations., Results: 263 patients were included (96 AC, 167 BC). AC was older than BC (60.0 vs 54.6, p = 0.025) and had lower BMI (27.1 vs 28.9, p = 0.047), but had similar CCI (3.2 vs 2.9 p = 0.312), and ASA Classification (2.5 vs 2.5, p = 0.790). Surgical characteristics, including levels fused (10.6 vs 10.7, p = 0.839), levels decompressed (1.29 vs 1.25, p = 0.863), 3 column osteotomies (10.4% vs 18.6%, p = 0.080), anterior column release (9.4% vs 12.6%, p = 0.432), and revision cases (53.1% vs 52.4%, p = 0.911) were similar between AC and BC. AC had lower EBL (1.1 vs 1.9L, p < 0.001) and fewer total intraoperative complications (16.7% vs 34.1%, p = 0.002), including fewer dural tears (4.2% vs 12.6%, p = 0.025), delayed extubations (8.3% vs 22.8%%, p = 0.003), and massive blood loss (4.2% vs 13.2%, p = 0.018). Length of stay (LOS) was similar between groups (7.2 vs 8.2 days, 0.251). AC had a lower incidence of deep surgical site infections (SSI, 1.0% vs 6.6%, p = 0.038), but a higher rate of hypotension requiring vasopressor therapy (18.8% vs 4.8%, p < 0.001). Other postoperative complications were similar between groups. AC had lower rates of reoperation at 30 (2.1% vs 8.4%, p = 0.040) and 90 days (3.1 vs 12.0%, p = 0.014) and lower readmission rates at 30 (3.1% vs 10.2%, p = 0.038) and 90 days (6.3 vs 15.0%, p = 0.035). On logistic regression, AC patients had higher odds of hypotension requiring vasopressor therapy and lower odds of delayed extubation, intraoperative RBC, and intraoperative salvage blood., Conclusions: Following implementation of a multidisciplinary high-risk case conference, 30- and 90-day reoperation and readmission rates, intraoperative complications, and postoperative deep SSIs decreased. Hypotensive events requiring vasopressors increased, but did not result in longer LOS or greater readmissions. These associations suggest a multidisciplinary conference may help improve quality and safety for high-risk spine patients. particularly through minimizing complications and optimizing outcomes in complex spine surgery., (© 2023. The Author(s), under exclusive licence to Scoliosis Research Society.)

Study Design: Retrospective analysis of outcomes in cervical spine and shoulder arthroscopy patients., Objective: The objective of this study is to assess differential improvements in health-related quality of life for cervical spine surgery compared with shoulder surgery., Summary of Background Data: An understanding of outcome differences between different types of orthopedic surgeries is helpful in counseling patients about expected postoperative recovery. This study compares outcomes in patients undergoing cervical spine surgery with arthroscopic shoulder surgery using computer-adaptive Patient-reported Outcome Information System scores., Materials and Methods: Patients undergoing cervical spine surgery (1-level or 2-level anterior cervical discectomy and fusion, cervical disc replacement) or arthroscopic shoulder surgery (rotator cuff repair±biceps tenodesis) were grouped. Patient-reported Outcome Information System scores of physical function, pain interference, and pain intensity at baseline and at 3, 6, and 12 months were compared using paired t tests., Results: Cervical spine (n=127) and shoulder (n=91) groups were similar in sex (25.8% vs. 41.8% female, P =0.731) but differed in age (51.6±11.6 vs. 58.60±11.2, P <0.05), operative time (148.3±68.6 vs. 75.9±26.9 min, P <0.05), American Society of Anesthesiologists (ASAs) (2.3±0.6 vs. 2.0±0.5, P =0.001), smoking status (15.7% vs. 4.4%, P =0.008), and length of stay (1.1±1.0 vs. 0.3±0.1, P =0.000). Spine patients had worse physical function (36.9 ±12.6 vs. 49.4±8.6, P <0.05) and greater pain interference (67.0±13.6 vs. 61.7±4.8, P =0.001) at baseline. Significant improvements were seen in all domains by 3 months for both groups, except for physical function after shoulder surgery. Spine patients had greater physical function improvements at all timepoints (3.33 vs. -0.43, P =0.003; 4.81 vs. 0.08, P =0.001; 6.5 vs. -5.24, P =<0.05). Conversely, shoulder surgery patients showed better 6-month improvement in pain intensity over spine patients (-8.86 vs. -4.46, P =0.001), but this difference resolved by 12 months., Conclusions: Cervical spine patients had greater relative early improvement in physical function compared with shoulder patients, whereas pain interference and intensity did not significantly differ between the 2 groups after surgery. This will help in counseling patients about relative difference in recovery and improvement between the 2 surgery types., Level of Evidence: III., Competing Interests: L.M.J. has received research support from Arthrex Inc., Mitek, and Smith & Nephew and publishing royalties from Wolters Kluwer Health—Lippincott Williams & Wilkins and is on the editorial or governing board for the Journal of Bone and Joint Surgery and the Bulletin for the Hospital for Joint Diseases. M.S.V. has received consulting fees from Acumed, LLC and Exactech Inc. and is on the editorial or governing board for American Journal of Orthopedics, American Shoulder and Elbow Surgeons, and Techniques in Orthopedics. K.A.C. has received research support from Stryker and consulting fees from Mitek, and is a board or committee member for AAOS and AANA. A.J.B. has received grants or contracts from Nuvasive; royalties from Nuvasive, Altus Spine, and Evolution Spine; and consulting fees from Nuvasive, Medtronic, and Evolution Spine. T.S.P. has received consulting fees from Globus Medical, Medicrea, Medtronic, Nuvasive, and Stryker and holds stock or stock options in Spine Align and Torus Medical. C.R.F. has received consulting fees from Stryker/K2M, Globus, Zimmer-Biomet, Amplify, and Life-Spine. The remaining authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The human gut microbiota produces dozens of small molecules that circulate in blood, accumulate to comparable levels as pharmaceutical drugs, and influence host physiology. Despite the importance of these metabolites to human health and disease, the origin of most microbially-produced molecules and their fate in the host remains largely unknown. Here, we uncover a host-microbe co-metabolic pathway for generation of hippuric acid, one of the most abundant organic acids in mammalian urine. Combining stable isotope tracing with bacterial and host genetics, we demonstrate reduction of phenylalanine to phenylpropionic acid by gut bacteria; the host re-oxidizes phenylpropionic acid involving medium-chain acyl-CoA dehydrogenase (MCAD). Generation of germ-free male and female MCAD -/- mice enabled gnotobiotic colonization combined with untargeted metabolomics to identify additional microbial metabolites processed by MCAD in host circulation. Our findings uncover a host-microbe pathway for the abundant, non-toxic phenylalanine metabolite hippurate and identify β-oxidation via MCAD as a novel mechanism by which mammals metabolize microbiota-derived metabolites., (© 2023. The Author(s).)

Study Design: A single-center, retrospective review of prospectively collected data on patients who underwent single-level anterior cervical discectomy and fusions (ACDFs) between October 2014 and October 2019., Objective: To investigate the effect of perioperative narcotic consumption and amount of narcotic prescribed at discharge on patient satisfaction with pain control after single-level ACDF., Summary of Background Data: Prior research has demonstrated that opioid prescription habits may be related to physician desire to produce superior patient satisfaction with pain control., Methods: Patients with complete Press-Ganey Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey information were analyzed. Inpatient opioid prescriptions were recorded and converted to milligram morphine equivalents (MME) and tablets of 5 mg oxycodone. HCAHPS scores were converted to a Likert-type 5-point scale., Results: A total of 47 patients met inclusion criteria for this study. Average age was 48.1±10.9 y. Average inpatient opioids prescribed was 102±106 MME. Average opioids prescribed at discharge was 437±342 MME. No statistically significant correlation was found between satisfaction with pain control and opioid consumption while in the hospital [r=-0.106, P=0.483]. Similarly, there was no statistically significant correlation between satisfaction with pain control and opioids prescribed upon discharge [r=-0.185, P=0.219]. No statistically significant correlation was found between date of surgery and inpatient MME consumption [r=-0.113, P=0.450]. Interestingly, more opioids were prescribed at discharge the earlier the date of surgery [r=-0.426, P=0.003]. For every additional month further along in the study period, the odds of a patient reporting a top box score for satisfaction with pain control increased by 5.5% [P=0.025]., Conclusion: Our study found no correlation between patient satisfaction with pain control and inpatient opioid dosage or outpatient prescription dosage after single-level ACDF. Moreover, satisfaction with pain control increased over time despite a decrease in MME prescribed at discharge. This suggests that factors other than narcotic consumption play a more important role in patient satisfaction with pain control., Level of Evidence: Level III., Competing Interests: C.R.F.: DePuy, A Johnson & Johnson Company: paid consultant. Nuvasive: paid consultant. T.S.P.: Globus Medical: paid consultant. Innovasis: paid consultant. K2M: paid consultant. Medicrea International: paid consultant. Nuvasive: paid consultant. Torus Medical: stock or stock options. A.J.B.: Corin USA: research support. Nuvasive: paid consultant. Stryker: paid consultant. The remaining authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Abundant literature exists describing the incidence of dysphagia following anterior cervical surgery; however, there is a paucity of literature detailing the incidence of dysphagia following posterior cervical procedures. Further characterization of this complication is important for guiding clinical prevention and management. Patients ≥ 18 years of age underwent posterior cervical fusion with laminectomy or laminoplasty between C1-T1. Pre- and post-operative dysphagia was assessed by a speech language pathologist. The patient cohort was categorized by approach: Laminectomy + Fusion (LF) and Laminoplasty (LP). Patients were excluded from radiographic analyses if they did not have both baseline and follow-up imaging. The study included 147 LF and 47 LP cases. There were no differences in baseline demographics. There were three patients with new-onset dysphagia in the LF group (1.5% incidence) and no new cases in the LP group (p = 1.000). LF patients had significantly higher rates of post-op complications (27.9% LF vs. 8.5% LP, p = 0.005) but not intra-op complications (6.1% LF vs. 2.1% LP, p = 0.456). Radiographic analysis of the entire cohort showed no significant changes in cervical lordosis, cSVA, or T1 slope. Both group comparisons showed no differences in incidence of dysphagia pre and post operatively. Based on this study, the likelihood of developing dysphagia after LF or LP are similarly low with a new onset dysphagia rate of 1.5%., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Study Design: Retrospective comparative; LOE-3., Objective: The purpose of this study was to investigate what effect, if any, an institutional opioid reduction prescribing policy following one- or two-level lumbar fusion has on Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey results., Summary of Background Data: Previous research has demonstrated that high levels of opioid-prescribing may be related, in part, to a desire to produce superior patient satisfaction., Methods: A retrospective review of prospectively collected data was conducted on patients who underwent one- or two-level lumbar fusions L3-S1 between October 2014 and October 2019 at a single institution. Patients with complete survey information were included in the analysis. Patients with a history of trauma, fracture, spinal deformity, fusions more than two levels, or prior lumbar fusion surgery L3-S1 were excluded. Cohorts were based on date of surgery relative to implementation of an institutional opioid reduction policy, which commenced in October 1, 2018. To better compare groups, opioid prescriptions were converted into milligram morphine equivalents (MME)., Results: A total of 330 patients met inclusion criteria: 259 pre-protocol, 71 post-protocol. There were 256 one-level fusions and 74 two-level fusions included. There were few statistically significant differences between groups with respect to patient demographics (P > 0.05) with the exception of number of patients who saw the pain management service, which increased from 36.7% (95) pre-protocol to 59.2% (42) post-protocol; P < 0.001. Estimated blood loss (EBL) decreased from 533 ± 571 mL to 346 ± 328 mL (P = 0.003). Percentage of patients who underwent concomitant laminectomy decreased from 71.8% to 49.3% (P < 0.001). Average opioids prescribed on discharge in the pre-protocol period was 534 ± 425 MME, compared to after initiation of the protocol, that is 320 ± 174 MME (P < 0.001). There was no statistically significant difference with respect to satisfaction with pain control, 4.49 ± 0.85 pre-protocol versus 4.51 ± 0.82 post-protocol (P = 0.986)., Conclusion: A reduction in opioids prescribed at discharge after one- or two-level lumbar fusion is not associated with any statistically significant change in patient satisfaction with pain management, as measured by the HCAHPS survey.Level of Evidence: 3., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The enteric pathogen Clostridioides difficile (Cd) is responsible for a toxin-mediated infection that causes more than 200,000 recorded hospitalizations and 13,000 deaths in the United States every year 1 . However, Cd can colonize the gut in the absence of disease symptoms. Prevalence of asymptomatic colonization by toxigenic Cd in healthy populations is high; asymptomatic carriers are at increased risk of infection compared to noncolonized individuals and may be a reservoir for transmission of Cd infection 2,3 . Elucidating the molecular mechanisms by which Cd persists in the absence of disease is necessary for understanding pathogenesis and developing refined therapeutic strategies. Here, we show with gut microbiome metatranscriptomic analysis that mice recalcitrant to Cd infection and inflammation exhibit increased community-wide expression of arginine and ornithine metabolic pathways. To query Cd metabolism specifically, we leverage RNA sequencing in gnotobiotic mice infected with two wild-type strains (630 and R20291) and isogenic toxin-deficient mutants of these strains to differentiate inflammation-dependent versus -independent transcriptional states. A single operon encoding oxidative ornithine degradation is consistently upregulated across non-toxigenic Cd strains. Combining untargeted and targeted metabolomics with bacterial and host genetics, we demonstrate that both diet- and host-derived sources of ornithine provide a competitive advantage to Cd, suggesting a mechanism for Cd persistence within a non-inflammatory, healthy gut., (© 2022. The Author(s).)

Background Context: The COVID-19 pandemic caused nationwide suspensions of elective surgeries due to reallocation of resources to the care of COVID-19 patients. Following resumption of elective cases, a significant proportion of patients continued to delay surgery, with many yet to reschedule, potentially prolonging their pain and impairment of function and causing detrimental long-term effects., Purpose: The aim of this study was to examine differences between patients who have and have not rescheduled their spine surgery procedures originally cancelled due to the COVID-19 pandemic, and to evaluate the reasons for continued deferment of spine surgeries even after the lifting of the mandated suspension of elective surgeries., Study Design/setting: Retrospective case series at a single institution PATIENT SAMPLE: Included were 133 patients seen at a single institution where spine surgery was canceled due to a state-mandated suspension of elective surgeries from March to June, 2020., Outcome Measures: The measures assessed included preoperative diagnoses and neurological dysfunction, surgical characteristics, reasons for surgery deferment, and PROMIS scores of pain intensity, pain interference, and physical function., Methods: Patient electronic medical records were reviewed. Patients who had not rescheduled their canceled surgery as of January 31, 2021, and did not have a reason noted in their charts were called to determine the reason for continued surgery deferment. Patients were divided into three groups: early rescheduled (ER), late rescheduled (LR), and not rescheduled (NR). ER patients had a date of surgery (DOS) prior to the city's Phase 4 reopening on July 20, 2020; LR patients had a DOS on or after that date. Statistical analysis of the group findings included analysis of variance with Tukey's honestly significant difference (HSD) post-hoc test, independent samples T-test, and chi-square analysis with significance set at p≤.05., Results: Out of 133 patients, 47.4% (63) were in the ER, 15.8% (21) in the LR, and 36.8% (49) in the NR groups. Demographics and baseline PROMIS scores were similar between groups. LR had more levels fused (3.6) than ER (1.6), p= .018 on Tukey HSD. NR (2.1) did not have different mean levels fused than LR or ER, both p= >.05 on Tukey HSD. LR had more three column osteotomies (14.3%) than ER and (1.6%) and NR (2.0%) p=.022, and fewer lumbar microdiscectomies (0%) compared to ER (20.6%) and NR (10.2%), p=.039. Other surgical characteristics were similar between groups. LR had a longer length of stay than ER (4.2 vs 2.4, p=.036). No patients in ER or LR had a nosocomial COVID-19 infection. Of NR, 2.0% have a future surgery date scheduled and 8.2% (4) are acquiring updated exams before rescheduling. 40.8% (20; 15.0% total cohort) continue to defer surgery over concern for COVID-19 exposure and 16.3% (8) for medical comorbidities. 6.1% (3) permanently canceled for symptom improvement. 8.2% (4) had follow-up recommendations for non-surgical management. 4.1% (2) are since deceased., Conclusion: Over 1/3 of elective spine surgeries canceled due to COVID-19 have not been performed in the 8 months from when elective surgeries resumed in our institution to the end of the study. ER patients had less complex surgeries planned than LR. NR patients continue to defer surgery primarily over concern for COVID-19 exposure. The toll on the health of these patients as a result of the delay in treatment and on their lives due to their inability to return to normal function remains to be seen., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Study Design: Retrospective cohort analysis., Objective: To compare outcomes of plastic versus spine surgeon wound closure in revision 1 to 4 level thoracolumbar fusions., Summary of Background Data: Plastic surgeons perform layered musculocutaneous flap closures in high-risk spine patients such as revision posterior spinal fusion and complex deformity correction surgeries. Few studies have assessed outcomes of revision fusion performed with plastic surgical closures, particularly in nondeformity thoracolumbar spinal surgery., Methods: A retrospective review of 1 to 4 level revision thoracolumbar fusion performed by Orthopedic or Neurosurgical spine surgeons. Patient charts were reviewed for demographics and perioperative outcomes. Patients were divided into two cohorts: wound closures performed by spine surgeons and those closed by plastic surgeons. Outcomes were analyzed before and after propensity score match for prior levels fused, iliac fixation, and levels fused at index surgery. Significance was set at P < 0.05., Results: Three hundred fifty-seven (87.3%) spine surgeon (SS) and 52 (12.7%) plastic surgeon (PS) closures were identified. PS group had significantly higher number of levels fused at index (PS 2.7 ± 1.0 vs. SS 1.8 ± 0.9, P < 0.001) and at prior surgeries (PS 1.8 ± 1.2 vs. SS 1.0 ± 0.9, P < 0.001), and rate of iliac instrumentation (PS 17.3% vs. SS 2.8%, P < 0.001). Plastics closure was an independent risk factor for length of stay  > 5 days (odds ratio 2.3) and postoperative seroma formation (odds ratio 7.8). After propensity score match, PS had higher rates of seromas (PS 36.5% vs. SS 3.8%, P < 0.001). There were no differences between PS and SS groups in surgical outcomes, perioperative complication, surgical site infection, seroma requiring aspiration, or return to operating room at all time points until follow-up (P > 0.05 for all)., Conclusion: Plastic spinal closure for 1 to 4 level revision posterior thoracolumbar fusions had no advantage in reducing wound complications over spine surgeon closure but increased postoperative seroma formation.Level of Evidence: 4., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Imbalance in the metabolic pathway linking excitatory and inhibitory neurotransmission has been implicated in multiple psychiatric and neurologic disorders. Recently, we described enantiomer-specific effects of 2-methylglutamate, which is not decarboxylated to the corresponding methyl analogue of gamma-aminobutyric acid (GABA): 4-aminopentanoic acid (4APA). Here, we tested the hypothesis that 4APA also has enantiomer-specific actions in brain. Mouse cerebral synaptosome uptake (nmol/mg protein over 30 min) of (R)-4APA or (S)-4APA was time and temperature dependent; however, the R enantiomer had greater uptake, reduction of endogenous GABA concentration, and release following membrane depolarization than did the S enantiomer. (S)-4APA exhibited some weak agonist (GABA A α4β3δ, GABA A α5β2γ2, and GABA B B1/B2) and antagonist (GABA A α6β2γ2) activity while (R)-4APA showed weak agonist activity only with GABAA α5β2γ2. Both 4APA enantiomers (100 mg/kg IP) were detected in mouse brain 10 min after injection, and by 1 hr had reached concentrations that were stable over 6 hr; both enantiomers were cleared rapidly from mouse serum over 6 hr. Two-month-old mice had no mortality following 100-900 mg/kg IP of each 4APA enantiomer but did have similar dose-dependent reduction in distance moved in a novel cage. Neither enantiomer at 30 or 100 mg/kg impacted outcomes in 23 measures of well-being, activity chamber, or withdrawal from hot plate. Our results suggest that enantiomers of 4APA are active in mouse brain, and that (R)-4APA may act as a novel false neurotransmitter of GABA. Future work will focus on disease models and on possible applications as neuroimaging agents., (© 2021 International Society for Neurochemistry.)

Gut microorganisms modulate host phenotypes and are associated with numerous health effects in humans, ranging from host responses to cancer immunotherapy to metabolic disease and obesity. However, difficulty in accurate and high-throughput functional analysis of human gut microorganisms has hindered efforts to define mechanistic connections between individual microbial strains and host phenotypes. One key way in which the gut microbiome influences host physiology is through the production of small molecules 1-3 , yet progress in elucidating this chemical interplay has been hindered by limited tools calibrated to detect the products of anaerobic biochemistry in the gut. Here we construct a microbiome-focused, integrated mass-spectrometry pipeline to accelerate the identification of microbiota-dependent metabolites in diverse sample types. We report the metabolic profiles of 178 gut microorganism strains using our library of 833 metabolites. Using this metabolomics resource, we establish deviations in the relationships between phylogeny and metabolism, use machine learning to discover a previously undescribed type of metabolism in Bacteroides, and reveal candidate biochemical pathways using comparative genomics. Microbiota-dependent metabolites can be detected in diverse biological fluids from gnotobiotic and conventionally colonized mice and traced back to the corresponding metabolomic profiles of cultured bacteria. Collectively, our microbiome-focused metabolomics pipeline and interactive metabolomics profile explorer are a powerful tool for characterizing microorganisms and interactions between microorganisms and their host., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: The goal of this study was to reliably predict sagittal and coronal spinal alignment with clinical photographs by using markers placed at easily localized anatomical landmarks., Methods: A consecutive series of patients with adult spinal deformity were enrolled from a single center. Full-length standing radiographs were obtained at the baseline visit. Clinical photographs were taken with reflective markers placed overlying C2, S1, the greater trochanter, and each posterior-superior iliac spine. Sagittal radiographic parameters were C2 pelvic angle (CPA), T1 pelvic angle (TPA), and pelvic tilt. Coronal radiographic parameters were pelvic obliquity and T1 coronal tilt. Linear regressions were performed to evaluate the relationship between radiographic parameters and their photographic "equivalents." The data were reanalyzed after stratifying the cohort into low-body mass index (BMI) (< 30) and high-BMI (≥ 30) groups. Interobserver and intraobserver reliability was assessed for clinical measures via intraclass correlation coefficients (ICCs)., Results: A total of 38 patients were enrolled (mean age 61 years, mean BMI 27.4 kg/m2, 63% female). All regression models were significant, but sagittal parameters were more closely correlated to photographic parameters than coronal measurements. TPA and CPA had the strongest associations with their photographic equivalents (both r2 = 0.59, p < 0.001). Radiographic and clinical parameters tended to be more strongly correlated in the low-BMI group. Clinical measures of TPA and CPA had high intraobserver reliability (all ICC > 0.99, p < 0.001) and interobserver reliability (both ICC > 0.99, p < 0.001)., Conclusions: The photographic measures of spinal deformity developed in this study were highly correlated with their radiographic counterparts and had high inter- and intraobserver reliability. Clinical photography can not only reduce radiation exposure in patients with adult spinal deformity, but also be used to assess deformity when full-spine radiographs are unavailable.

Imbalance of excitatory and inhibitory neurotransmission is implicated in a wide range of psychiatric and neurologic disorders. Here we tested the hypothesis that insertion of a methyl group on the stereogenic alpha carbon of L-Glu or L-Gln would impact the γ-aminobutyric acid (GABA) shunt and the glutamate-glutamine cycle. (S)-2-methylglutamate, or (S)-2MeGlu, was efficiently transported into brain and synaptosomes where it was released by membrane depolarization in a manner equivalent to endogenous L-Glu. (R)-2MeGlu was transported less efficiently into brain and synaptosomes but was not released by membrane depolarization. Each enantiomer of 2MeGlu had limited activity across a panel of over 30 glutamate and GABA receptors. While neither enantiomer of 2MeGlu was metabolized along the GABA shunt, (S)-2MeGlu was selectively converted to (S)-2-methylglutamine, or (S)-2MeGln, which was subsequently slowly hydrolyzed back to (S)-2MeGlu in brain. rac-2MeGln was also transported into brain, with similar efficiency as (S)-2MeGlu. A battery of behavioral tests in young adult wild type mice showed safety with up to single 900 mg/kg dose of (R)-2MeGlu, (S)-2MeGlu, or rac-2MeGln, suppressed locomotor activity with single ≥ 100 mg/kg dose of (R)-2MeGlu or (S)-2MeGlu. No effect on anxiety or hippocampus-dependent learning was evident. Enantiomers of 2MeGlu and 2MeGln show promise as potential pharmacologic agents and imaging probes for cells that produce or transport L-Gln.

Study Design: This was a single-center retrospective review., Objectives: To explore how age and gender affect PROMIS scores compared with traditional health-related quality of life (HRQL) in spine patients., Methods: Patients presenting with a primary complaint of back pain (BP) or neck pain (NP) were included. Legacy HRQLs were Oswestry Disability Index (ODI), Neck Disability Index (NDI), and Visual Analogue Scale (VAS). PROMIS Physical Function (PF), Pain Intensity (Int), and Pain Interference (Inf) were also administered to patients in a clinical setting. Patients were grouped by chief complaint, age (18-44, 45-64, 65+ years) and gender. Two parallel analyses were conducted to identify the effects of age and gender on patient-reported outcomes. Age groups were compared after propensity-score matching by VAS-pain and gender. Separately, genders were compared after propensity-score matching by age and VAS-pain., Results: A total of 484 BP and 128 NP patients were matched into gender cohorts (n = 201 in each BP group, 46 in each NP group). Among BP patients, female patients demonstrated worse disability by ODI (44.15 vs 38.45, P = .005); PROMIS-PF did not differ by gender. Among NP patients, neither legacy HRQLs nor PROMIS differed by gender when controlling for NP and age. BP and NP patients were matched into age cohorts (n = 135 in each BP group and n = 14 in each BP group). Among BP patients, ANOVA revealed differences between groups when controlling for BP and gender: ODI ( P < .001), PROMIS-PF ( P = .018), PROMIS-Int ( P < .001) PROMIS-Inf ( P < .001). Among NP patients, matched age groups differed significantly in terms of NDI ( P = .032) and PROMIS-PF ( P = .022) but not PROMIS-Int or PROMIS-Inf., Conclusions: Age and gender confound traditional HRQLs as well as PROMIS domains. However, PROMIS offers age and gender-specific scores, which traditional HRQLs lack.

Background: As the opioid crisis has gained national attention, there have been increasing efforts to decrease opioid usage. Simultaneously, patient satisfaction has been a crucial metric in the American health care system and has been closely linked to effective pain management in surgical patients. The purpose of this study was to examine rates of pain medication prescription and concurrent patient satisfaction in spine surgery patients., Methods: A total of 1729 patients undergoing spine surgery between June 25, 2017, and June 30, 2018, at a single institution by surgeons performing ≥20 surgeries per quarter, with medication data during hospitalization available, were assessed. Patients were evaluated for nonopioid pain medication prescription rates and morphine milligram equivalents (MME) of opioids used during hospitalization. Of the total cohort, 198 patients were evaluated for Press Ganey Satisfaction Survey responses. A χ 2 test of independence was used to compare percentages, and 1-way analysis of variance was used to compare means across quarters., Results: The mean total MME per patient hospitalization was 574.46, with no difference between quarters. However, mean MME per day decreased over time ( P = .048), with highest mean 91.84 in Quarter 2 and lowest 77.50 in Quarter 4. Among all procedures, acetaminophen, nonsteroidal anti-inflammatory drugs, and steroid prescription rates increased, whereas benzodiazepine and γ-aminobutyric acid-analog prescriptions decreased. There were no significant differences between quarters for mean hospital ratings ( P = .521) nor for responses to questions from the Press Ganey Satisfaction Survey regarding how often staff talk about pain ( P = .164), how often staff talk about pain treatment ( P = .595), or whether patients recommended the hospital ( P = .096). There were also no differences between quarters for responses in all other patient satisfaction questions ( P value range, .359-.988)., Conclusions: Over the studied time period, opioid use decreased and nonopioid prescriptions increased during hospitalization, whereas satisfaction scores remained unchanged. These findings indicate an increasing effort in reducing opioid use among providers and suggest the ability to do so without affecting overall satisfaction rates., Level of Evidence: 4., Clinical Relevance: The opioid epidemic has highlighted the need to reduce opioid usage in orthopedic spine surgery. This study reviews the trends for inpatient management of post-op pain in orthopedic spine surgery patients in relation to patient satisfaction. There was a significant increase in non-opioid analgesic pain medications, and a reduction in opioids during the study period. During this time, patient satisfaction as measured by Press-Ganey surveys did not show a decrease. This demonstrates that treatment of post-operative pain in orthopedic spine surgery patients can be managed with less opioids, more multimodal analgesia, and patient satisfaction will not be affected., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2020 ISASS.)

Background: Bone morphogenetic protein (BMP) and allograft containing mesenchymal stem cells (live cell) are popular biologic substitutes for iliac crest autograft used in transforaminal lumbar interbody fusion (TLIF). Use of these agents in the pathogenesis of postoperative radiculitis remains controversial. Recent studies have independently linked minimally invasive (MIS) TLIF with increased radiculitis risk compared to open TLIF. The purpose of this study was to assess the rate of postoperative radiculitis in open and MIS TLIF patients along with its relationship to concurrent biologic adjuvant use., Methods: Patients ≥18 years undergoing single-level TLIF from June 2012 to December 2018 with minimum 1-year follow-up were included. Outcome measures were rate of radiculitis, intra- and postoperative complications, revision surgery; length of stay (LOS), and estimated blood loss (EBL)., Results: There were 397 patients: 223 with open TLIFs, 174 with MIS TLIFs. One hundred and fifty-nine surgeries used bone morphogenetic protein (BMP), 26 live cell, 212 neither. Open TLIF: higher mean EBL, LOS, and Charlson Comorbidity Index (CCI) than MIS. Postoperative radiculitis in 37 patients (9.32% overall): 16 cases MIS BMP (15.69% of their cohort), 6 MIS without BMP (8.33%), 5 open BMP (8.77%), 10 open without BMP (6.02%). MIS TLIF versus open TLIF: no differences in 1-year reoperation rates, infection/wound complication, pseudarthrosis, or postoperative complication rate. BMP versus non-BMP: no differences in reoperation rates, infection/wound complication, pseudarthrosis, or postoperative complication rate. Multivariate logistic regression found that neither BMP ( P = .109) nor MIS ( P = .314) was an independent predictor for postoperative radiculitis when controlled for age, gender, body mass index, and CCI. Using paired open and MIS groups (N = 168 each) with propensity score matching, these variables were still not independently associated with radiculitis ( P = .174 BMP, P = .398 MIS). However, the combination of MIS with BMP was associated with increased radiculitis risk in both the entire patient cohort (odds ratio [OR]: 2.259 [1.117-4.569], P = .023, N = 397) and PSM cohorts (OR: 2.196 [1.045-4.616], P = .038, N = 336) compared to other combinations of surgical approach and biologic use., Conclusion: Neither the MIS approach nor BMP use is an independent risk factor for post-TLIF radiculitis. However, risk of radiculitis significantly increases when they are used in tandem. This should be considered when selecting biological adjuvants for MIS TLIF., Level of Evidence: 3., (This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2020 ISASS.)

N-acyl amino acids are a family of cold-inducible circulating lipids that stimulate thermogenesis. Their biosynthesis is mediated by a secreted enzyme called PM20D1. The extracellular mechanisms that regulate PM20D1 or N-acyl amino acid activity in the complex environment of blood plasma remains unknown. Using quantitative proteomics, here we show that PM20D1 circulates in tight association with both low- and high-density lipoproteins. Lipoprotein particles are powerful co-activators of PM20D1 activity in vitro and N-acyl amino acid biosynthesis in vivo. We also identify serum albumin as a physiologic N-acyl amino acid carrier, which spatially segregates N-acyl amino acids away from their sites of production, confers resistance to hydrolytic degradation, and establishes an equilibrium between thermogenic "free" versus inactive "bound" fractions. These data establish lipoprotein particles as principal extracellular sites of N-acyl amino acid biosynthesis and identify a lipoprotein-albumin network that regulates the activity of a circulating thermogenic lipid family., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Study Design: Retrospective cohort study of prospective patients undergoing minimally invasive lumbar fusion at a single academic institution., Objective: To assess differences in perioperative outcomes between primary and revision MIS (minimally invasive surgical) lumbar interbody fusion patients and compare with those undergoing corresponding open procedures., Methods: Patients ≥18 years old undergoing lumbar interbody fusion were grouped by surgical technique: MIS or open. Patients within each group were propensity score matched for comorbidities and levels fused. Patient demographics, surgical factors, and perioperative complication incidences were compared between primary and revision cases using means comparison tests, as appropriate., Results: Of the 214 lumbar interbody fusion patients included after propensity score matching, 44 (21%) cases were MIS, and 170 (79%) were open. For MIS patients, there were no significant differences between primary and revision cases in estimated blood loss (EBL; 344 vs 299 cm 3 , P = .682); however, primary cases had longer operative times (301 vs 246 minutes, P = .029). There were no differences in length of stay (LOS), intensive care unit LOS, readmission, and intraoperative or postoperative complications (all P > .05). For open patients, there were no differences between primary and revision cases in EBL ( P > .05), although revisions had longer operative times (331 vs 278 minutes, P = .018) and more postoperative complications (61.7% vs 23.8%, P < .001). MIS revision procedures were shorter than open revisions (182 vs 213 minutes, P = .197) with significantly less EBL (294 vs 965 cm 3 , P < .001), shorter inpatient and intensive care unit LOS, and fewer postoperative complications (all P < .05)., Conclusions: Clinical outcomes of revision MIS lumbar interbody fusion were similar to those of primary surgery. Additionally, MIS techniques were associated with less EBL, shorter LOS, and fewer perioperative complications than corresponding open revisions.

Genome-wide analysis of the mode of action of GSK983, a potent antiviral agent, led to the identification of dihydroorotate dehydrogenase as its target along with the discovery that genetic knockdown of pyrimidine salvage sensitized cells to GSK983. Because GSK983 is an ineffective antiviral in the presence of physiological uridine concentrations, we explored combining GSK983 with pyrimidine salvage inhibitors. We synthesized and evaluated analogs of cyclopentenyl uracil (CPU), an inhibitor of uridine salvage. We found that CPU was converted into its triphosphate in cells. When combined with GSK983, CPU resulted in large drops in cellular UTP and CTP pools. Consequently, CPU-GSK983 suppressed dengue virus replication in the presence of physiological concentrations of uridine. In addition, the CPU-GSK983 combination markedly enhanced the effect of RNA-dependent RNA polymerase (RdRp) inhibition on viral infection. Our findings highlight a new host-targeting strategy for potentiating the antiviral activity of RdRp inhibitors., Competing Interests: Declaration of Interests A patent has been filed on this work by the Stanford University Office of Technology Licensing on behalf of Q.L, A.G, and C.K. with reference label S19-283. M.S. is a paid consultant for Riboscience LLD and Advisory Board Member for Tranquis Therapeutics and Angarus Therapeutics. The other authors declare no competing interests., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Purpose: Predictors of long-term opioid usage in TLIF patients have not been previously explored in the literature. We examined the effect of pre-operative narcotic use in addition to other predictors of the pattern and duration of post-operative narcotic usage., Methods: We conducted a retrospective cohort study at a single academic institution of patients undergoing a one- or two-level primary TLIF between 2014 and 2017. Total oral morphine milligram equivalents (MMEs) for inpatient use were calculated and used as the common unit of comparison., Results: A multivariate binary logistic regression (R 2  = 0.547, specificity 95%, sensitivity 58%) demonstrated that a psychiatric or chronic pain diagnosis (OR 3.95, p = 0.013, 95% CI 1.34-11.6), pre-operative opioid use (OR 8.65, p < 0.001, 95% CI 2.59-29.0), ASA class (OR 2.95, p = 0.025, 95% CI 1.14-7.63), and inpatient total MME (1.002, p < 0.001, 95% CI 1.001-1.003) were positive predictors of prolonged opioid use at 6-month follow-up, while inpatient muscle relaxant use (OR 0.327, p = 0.049, 95% CI 0.108-0.994) decreased the probability of prolonged opioid use. Patients in the pre-operative opioid use group had a significantly higher rate of opioid usage at 6 weeks (79% vs. 46%, p < 0.001), 3 months (51% vs. 14%, p < 0.001), and 6 months (40% vs. 5%, p < 0.001)., Conclusions: Pre-operative opioid usage is associated with higher total inpatient opioid use and a significantly higher risk of long-term opiate usage at 6 months. Approximately 40% of pre-operative narcotic users will continue to consume narcotics at 6-month follow-up, compared with 5% of narcotic-naïve patients. These slides can be retrieved under Electronic Supplementary Material.

Study Design: Retrospective review of single institution., Objective: To assess the relationship between Patient-Reported Outcomes Measurement Information System (PROMIS) and Oswestry Disability Index (ODI) scores in thoracolumbar patients., Methods: Included: Patients ≥18 years with a thoracolumbar spine condition (spinal stenosis, disc herniation, low back pain, disc degeneration, spondylolysis). Bivariate correlations assessed the linear relationships between ODI and PROMIS (Physical Function, Pain Intensity, and Pain Interference). Correlation cutoffs assessed patients with high and low correlation between ODI and PROMIS. Linear regression predicted the relationship of ODI to PROMIS., Results: A total of 206 patients (age 53.7 ± 16.6 years, 49.5% female) were included. ODI correlated with PROMIS Physical Function ( r = -0.763, P < .001), Pain Interference ( r = 0.800, P < .001), and Pain Intensity ( r = 0.706, P < .001). ODI strongly predicted PROMIS for Physical Function ( R 2 = 0.58, P < .001), Pain Intensity ( R 2 = 0.50, P < .001), and Pain Interference ( R 2 = 0.64, P < .001); however, there is variability in PROMIS that ODI cannot account for. ODI questions about sitting and sleeping were weakly correlated across the 3 PROMIS domains. Linear regression showed overall ODI score as accounting for 58.3% ( R 2 = 0.583) of the variance in PROMIS Physical Function, 63.9% ( R 2 = 0.639) of the variance in Pain Interference score, and 49.9% ( R 2 = 0.499) of the variance in Pain Intensity score., Conclusions: There is a large amount of variability with PROMIS that cannot be accounted for with ODI. ODI questions regarding walking, social life, and lifting ability correlate strongly with PROMIS while sitting, standing, and sleeping do not. These results reinforce the utility of PROMIS as a valid assessment for low back disability, while indicating the need for further evaluation of the factors responsible for variation between PROMIS and ODI., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Peter G. Passias consults for Medicrea and SpineWave; is on the Scientific Advisory Board of Allosource; receives teaching/speaking from Zimmer Biomet and Globus; receives grant from CSRS; does a research study for Aesculap., (© The Author(s) 2019.)

The N-acyl amino acids are a family of bioactive lipids with pleiotropic physiologic functions, including in energy homeostasis. Their endogenous levels are regulated by an extracellular mammalian N-acyl amino acid synthase/hydrolase called PM20D1 (peptidase M20 domain containing 1). Using an activity-guided biochemical approach, we report the molecular identification of fatty acid amide hydrolase (FAAH) as a second intracellular N-acyl amino acid synthase/hydrolase. In vitro, FAAH exhibits a more restricted substrate scope compared to PM20D1. In mice, genetic ablation or selective pharmacological inhibition of FAAH bidirectionally dysregulates intracellular, but not circulating, N-acyl amino acids. Dual blockade of both PM20D1 and FAAH reveals a dramatic and non-additive biochemical engagement of these two enzymatic pathways. These data establish FAAH as a second intracellular pathway for N-acyl amino acid metabolism and underscore enzymatic division of labor as an enabling strategy for the regulation of a structurally diverse bioactive lipid family., Competing Interests: JK, ST, VL, WW, CF, JL No competing interests declared, (© 2020, Kim et al.)

Several Nocardia strains associated with nocardiosis, a potentially life-threatening disease, house a nonamodular assembly line polyketide synthase (PKS) that presumably synthesizes an unknown polyketide. Here, we report the discovery and structure elucidation of the NOCAP (nocardiosis-associated polyketide) aglycone by first fully reconstituting the NOCAP synthase in vitro from purified protein components followed by heterologous expression in E. coli and spectroscopic analysis of the purified products. The NOCAP aglycone has an unprecedented structure comprised of a substituted resorcylaldehyde headgroup linked to a 15-carbon tail that harbors two conjugated all- trans trienes separated by a stereogenic hydroxyl group. This report is the first example of reconstituting a trans -acyltransferase assembly line PKS in vitro and of using these approaches to "deorphanize" a complete assembly line PKS identified via genomic sequencing. With the NOCAP aglycone in hand, the stage is set for understanding how this PKS and associated tailoring enzymes confer an advantage to their native hosts during human Nocardia infections.

Background: Lumbar herniated nucleus pulposus (HNP) is a common spinal pathology often treated by microscopic lumbar discectomy (MLD), though prior reports have not demonstrated which preoperative MRI factors may contribute to significant clinical improvement after MLD., Purpose: To analyze the MRI characteristics in patients with HNP that predict meaningful clinical improvement in health-related quality of life scores (HRQoL) after MLD., Study Design/setting: Retrospective clinical and radiological study of patients undergoing MLD for HNP at a single institution over a 2-year period., Patient Sample: Eighty-eight patients receiving MLD treatment for HNP., Outcome Measures: Cephalocaudal Canal Migration; Canal & HNP Anterior-Posterior (AP) Lengths and Ratio; Canal & HNP Axial Areas and Ratio; Hemi-Canal & Hemi-HNP Axial Areas and Ratio; Disc appearance (black, gray, or mixed); Baseline (BL); and 3-month (3M) postoperative HRQoL scores., Methods: Patients >18 years old who received MLD for HNP with BL and 3M HRQoL scores of PROMIS (Physical Function, Pain Interference, and Pain Intensity), ODI, VAS Back, and VAS Leg scores were included. HNP and spinal canal measurements of cephalocaudal migration, AP length, area, hemi-area, and disc appearance were performed using T2 axial and sagittal MRI. HNP measurements were divided by corresponding canal measurements to calculate AP, Area, and Hemi-Area ratios. Using known minimal clinically important differences (MCID) for each ΔHRQoL score, patients were separated into two groups based on whether they reached MCID (MCID+) or did not reach MCID (MCID-). The MCID for PROMIS pain intensity was calculated using a decision tree. A linear regression illustrated correlations between PROMIS vs ODI and VAS Back/Leg scores. Independent t-tests and chi-squared tests were utilized to investigate significant differences in HNP measurements between the MCID+ and MCID- groups., Results: There were 88 MLD patients included in the study (Age=44.6±14.9, 38.6% female). PROMIS pain interference and pain intensity were strongly correlated with ODI and VAS Back/Leg (R≥0.505), and physical function correlated with ODI and VAS Back/Leg (R=-0.349) (all p<.01). The strongest MRI predictors of meeting HRQoL MCID were gray disc appearance, HNP area (>116.6 mm 2 ), and Hemi-Area Ratio (>51.8%). MCID+ patients were 2.7 times more likely to have a gray HNP MRI signal than a mixed or black HNP MRI signal in five out of six HRQoL score comparisons (p<.025). MCID+ patients had larger HNP areas than MCID- patients had in five out of six HRQoL score comparisons (116.6 mm 2 ±46.4 vs 90.0 mm 2 ±43.2, p<.04). MCID+ patients had a greater Hemi-Area Ratio than MCID- patients had in four out of six HRQoL score comparisons (51.8%±14.7 vs 43.9%±14.9, p<.05)., Conclusions: Patients who met MCID after MLD had larger HNP areas and larger Hemi-HNP Areas than those who did not meet MCID. These patients were also 2.7× more likely to have a gray MRI signal than a mixed or black MRI signal. When accounting for HNP area relative to canal area, patients who met MCID had greater Hemi-HNP canal occupation than patients who did not meet MCID. The results of this study suggest that preoperative MRI parameters can be useful in predicting patient-reported improvement after MLD., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Hospital-acquired venous thromboembolisms (HA-VTE) are a significant source of morbidity and mortality in spine surgery patients. The purpose of this study was to review HA-VTE rates at our institution and evaluate the prevalence of known risk factors in patients who developed HA-VTE among both neurosurgical and orthopedic spine surgeries., Methods: Retrospective chart reviews were conducted of all spine surgery patients from January 1, 2013, to July 31, 2017, to evaluate rates of HA-VTE and prevalence of known HA-VTE risk factors among these patients. Univariate and multivariate logistic regression analysis for categorical variables and independent Student t test for continuous variables were utilized with significance set at P  < .05., Results: The overall HA-VTE rate was 0.94% (0.61% orthopedic, 1.87% neurosurgery). Patients with VTEs had higher rates of thoracic procedure ( P  = .002), posterior approach ( P  = .001), diagnosis of fracture ( P  = .013) or flatback syndrome ( P  = .028), neurosurgery division ( P  < .001), and diagnosis-related group (DRG) of noncervical malignancy ( P  = .001). Patients with VTEs had lower rates of cervical procedure ( P  < .001), diagnosis of herniated nucleus pulposus ( P  = .006) and degenerative disc disease ( P  = .001), and DRG of cervical spine fusion ( P  < .001). In the patients who sustained VTE, the neurosurgical patients had higher rates of active cancer (22.86% vs 0%, P  = .004) and age >60 (80% vs 50%, P  < .001), and orthopedic patients had higher estimated blood loss (EBL) (2436 ml vs 1176 mL, P  = .006) and rates of anterior-posterior surgery (22.58% vs 0%, P  = .003). Neurosurgery department, diagnosis of fracture, and DRG of noncervical malignancy were found to be significant independent risks for developing HA-VTE. Cervical procedures were independently associated with significantly lower risk. Postoperative anticoagulation initiated sooner in neurosurgery patients (postoperative day 1.26 vs 3.19, P  < .001)., Conclusions: The overall HA-VTE rate at our institution was 0.94% (0.61% orthopedic, 1.87% neurosurgery). In patients who sustained VTE, neurosurgical patients had higher rates of active cancer and age >60 years, and orthopedic patients had higher EBL and rates of anterior-posterior surgery. This highlights the different patient populations between the 2 departments and the need for individualized thromboprophylaxis regimens., Level of Evidence: 4., Competing Interests: Disclosures and COI: Each institution obtained approval from its local institutional review board to enroll patients in the prospective database, and informed consent was obtained from each patient., (©International Society for the Advancement of Spine Surgery 2020.)

Consumption of glucosinolates, pro-drug-like metabolites abundant in Brassica vegetables, has been associated with decreased risk of certain cancers. Gut microbiota have the ability to metabolize glucosinolates, generating chemopreventive isothiocyanates. Here, we identify a genetic and biochemical basis for activation of glucosinolates to isothiocyanates by Bacteroides thetaiotaomicron, a prominent gut commensal species. Using a genome-wide transposon insertion screen, we identified an operon required for glucosinolate metabolism in B. thetaiotaomicron. Expression of BT2159-BT2156 in a non-metabolizing relative, Bacteroides fragilis, resulted in gain of glucosinolate metabolism. We show that isothiocyanate formation requires the action of BT2158 and either BT2156 or BT2157 in vitro. Monocolonization of mice with mutant BtΔ2157 showed reduced isothiocyanate production in the gastrointestinal tract. These data provide insight into the mechanisms by which a common gut bacterium processes an important dietary nutrient., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Study Design: Retrospective cohort study., Objective: To investigate radiological differences in lumbar disc herniations (herniated nucleus pulposus [HNP]) between patients receiving microscopic lumbar discectomy (MLD) and nonoperative patients., Methods: Patients with primary treatment for an HNP at a single academic institution between November 2012 to March 2017 were divided into MLD and nonoperative treatment groups. Using magnetic resonance imaging (MRI), axial HNP area; axial canal area; HNP canal compromise; HNP cephalad/caudal migration and HNP MRI signal (black, gray, or mixed) were measured. T test and chi-square analyses compared differences in the groups, binary logistic regression analysis determined odds ratios (ORs), and decision tree analysis compared the cutoff values for risk factors., Results: A total of 285 patients (78 MLD, 207 nonoperative) were included. Risk factors for MLD treatment included larger axial HNP area ( P < .01, OR = 1.01), caudal migration, and migration magnitude ( P < .05, OR = 1.90; P < .01, OR = 1.14), and gray HNP MRI signal ( P < .01, OR = 5.42). Cutoff values for risks included axial HNP area (70.52 mm 2 , OR = 2.66, P < .01), HNP canal compromise (20.0%, OR = 3.29, P < .01), and cephalad/caudal migration (6.8 mm, OR = 2.43, P < .01). MLD risk for those with gray HNP MRI signal (67.6% alone) increased when combined with axial HNP area >70.52 mm 2 (75.5%, P = .01) and HNP canal compromise >20.0% (71.1%, P = .05) cutoffs. MLD risk in patients with cephalad/caudal migration >6.8 mm (40.5% alone) increased when combined with axial HNP area and HNP canal compromise (52.4%, 50%; P < .01)., Conclusion: Patients who underwent MLD treatment had significantly different axial HNP area, frequency of caudal migration, magnitude of cephalad/caudal migration, and disc herniation MRI signal compared to patients with nonoperative treatment., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2019.)

In response to biotic stress, plants produce suites of highly modified fatty acids that bear unusual chemical functionalities. Despite their chemical complexity and proposed roles in pathogen defense, little is known about the biosynthesis of decorated fatty acids in plants. Falcarindiol is a prototypical acetylenic lipid present in carrot, tomato, and celery that inhibits growth of fungi and human cancer cell lines. Using a combination of untargeted metabolomics and RNA sequencing, we discovered a biosynthetic gene cluster in tomato (Solanum lycopersicum) required for falcarindiol production. By reconstituting initial biosynthetic steps in a heterologous host and generating transgenic pathway mutants in tomato, we demonstrate a direct role of the cluster in falcarindiol biosynthesis and resistance to fungal and bacterial pathogens in tomato leaves. This work reveals a mechanism by which plants sculpt their lipid pool in response to pathogens and provides critical insight into the complex biochemistry of alkynyl lipid production., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Low back pain is one of the most common reasons for physician visits, leading to high heath care costs and disability. Patients may present to primary care physicians, pain management physicians, chiropractors, physical therapists, or surgeons with these complaints. A thorough history and physical examination coupled with judicious use of advanced imaging studies will aid in determining the etiology of the pain. As most cases of low back pain are self-limited and will not develop into chronic pain, nonsurgical treatment is the mainstay. First-line treatment includes exercise, superficial heat, massage, acupuncture, or spinal manipulation. Pharmacologic treatment should be reserved for patients unresponsive to nonpharmacologic treatment and may include NSAIDs or muscle relaxants. Surgery is reserved for patients with pain nonresponsive to a full trial of nonsurgical interventions and with imaging studies which are concordant with physical examination findings.

Background: Physiotherapeutic scoliosis-specific exercise (PSSE) has proven to be an important treatment for patients with adolescent idiopathic scoliosis. However, there is a lack of understanding of the role of PSSE in older adults with spinal deformity., Methods: An electronic, 14-question survey with questions regarding the use of physical therapy (PT) and PSSE for adult spinal deformity was administered to all Scoliosis Research Society members. Physician location, age, specialty, years in experience, and management preferences were quantified using descriptive analyses., Results: Of the 98 surgeons who participated in this study, the majority of respondents were from North America (71.1%), and the mean age was 51.87 ± 10.93 years; approximately 98% of respondents were orthopedic surgeons, and 48.0% had been in practice for more than 21 years. Sixty-four percent reported they prescribed PT in their practice, with 52% of respondents often using PT as nonoperative treatment; 21.4%, preoperative; and 40.8% postoperative. The primary reason for PT referral was persistent pain (40.3%), followed by impairments to the patient's balance or gait (34.3%) and difficulty with daily living activities (25.4%). The primary indications for not referring postoperative patients to PT were lack of perceived value from PT (50%), lack of evidence supporting the benefits from PT (31.3%), and a lack of physical therapists appropriately trained for scoliosis (18.8%). Of the respondents, 74% were familiar with PSSE and 66% were comfortable prescribing PSSE postoperatively. In addition, 28% of respondents agreed that >12 weeks postoperation was the ideal time for PSSE referral, followed by 6 to 8 weeks postoperation (26.2%) and immediately postoperation (18%)., Conclusions: The results show that the majority of respondents prescribed PSSE solely for nonoperative treatment. Respondents who did not prescribe PSSE reported skepticism due to a lack of perceived value. This suggests the need for further research into the benefits of PSSE., Level of Evidence: 5., Clinical Relevance: Physiotherapeutic Scoliosis Specific Exercises (PSSE) is an important non-operative treatment for patients with Adolescent Idiopathic Scoliosis (AIS) but is understudied in Adult Spinal Deformity (ASD) patients, suggesting further clinical research. This study demonstrates that only two-thirds of the respondents familiar with PSSE were comfortable prescribing PSSE postoperatively suggesting the need for further research into the effectiveness and benefits of PSSE in ASD patients., Competing Interests: Disclosures and COI: The authors received no financial support for the research, authorship, and/or publication of this article and report no conflicts of interest., (©International Society for the Advancement of Spine Surgery 2019.)

The gut microbiota produce hundreds of molecules that are present at high concentrations in the host circulation. Unraveling the contribution of each molecule to host biology remains difficult. We developed a system for constructing clean deletions in Clostridium spp., the source of many molecules from the gut microbiome. By applying this method to the model commensal organism Clostridium sporogenes , we knocked out genes for 10 C. sporogenes -derived molecules that accumulate in host tissues. In mice colonized by a C. sporogenes for which the production of branched short-chain fatty acids was knocked out, we discovered that these microbial products have immunoglobulin A-modulatory activity., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Enzymes catalyze fundamental biochemical reactions that control cellular and organismal homeostasis. Here we present an approach for de novo biochemical pathway discovery across entire mammalian enzyme families using parallel viral transduction in mice and untargeted liquid chromatography-mass spectrometry. Applying this method to the M20 peptidases uncovers both known pathways of amino acid metabolism as well as a previously unknown CNDP2-regulated pathway for threonyl dipeptide catabolism. Ablation of CNDP2 in mice elevates threonyl dipeptides across multiple tissues, establishing the physiologic relevance of our biochemical assignments. Taken together, these data underscore the utility of parallel in vivo metabolomics for the family-wide discovery of enzymatic pathways., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Study Design: A retrospective cohort study from a single institution., Objective: The aim of this study was to assess the thresholds for postoperative opioid consumption, which are predictive of continued long-term opioid dependence., Summary of Background Data: The specific sum total of inpatient opioid consumption as a risk factor for long-term use after transforaminal lumbar interbody fusion (TLIF) has not been previously studied., Methods: Charts of patients who underwent a one, two, or three-level primary TLIF between 2014 and 2017 were reviewed. Total morphine milligram equivalents (MME) consumed was tabulated and separated into three categories based on ROC curve analysis of opioid utilization at 6-month follow-up. Multivariate binary regression analysis assessed these MME dosage categories. A further subanalysis grouped patients on the basis of whether they had used opioids preoperatively., Results: One hundred seventy-two patients met the inclusion criteria and were separated into groups who received less than 250 total inpatient MME (44%), between 250 and 500 total inpatient MME (26%), and greater than 500 total inpatient MME (27%). Patients undergoing a TLIF who received <250 total MME in the immediate postoperative period had a 3.73 (odds ratio) times smaller probability of requiring opioids at 6-month follow-up [P = 0.027, 95% confidence interval (95% CI) 0.084-0.86]. Patients who received >500 total MME had a 4.84 times greater probability (P = 0.002, 95% CI 1.8-13) of requiring opioids at 6-month follow-up. A subanalysis demonstrated individuals with preoperative opioid use who received <250 total MME had a 7.09 times smaller probability (P = 0.033, 95% CI 0.023-0.85) of requiring opioids at 6-month follow-up while those who received >500 total MME had a 5.43 times greater probability (P = 0.033, 95% CI 1.6-18) of requiring opioids at 6-month follow-up., Conclusion: Exceeding the threshold of 500 total MMEs in the immediate postoperative period after a TLIF is a significant risk factor that predicts continued opioid use at 6-month follow-up, particularly among patients with a history of preoperative opioid utilization., Level of Evidence: 3.

Antibody-drug conjugates (ADCs) selectively deliver chemotherapeutic agents to target cells and are important cancer therapeutics. However, the mechanisms by which ADCs are internalized and activated remain unclear. Using CRISPR-Cas9 screens, we uncover many known and novel endolysosomal regulators as modulators of ADC toxicity. We identify and characterize C18ORF8/RMC1 as a regulator of ADC toxicity through its role in endosomal maturation. Through comparative analysis of screens with ADCs bearing different linkers, we show that a subset of late endolysosomal regulators selectively influence toxicity of noncleavable linker ADCs. Surprisingly, we find cleavable valine-citrulline linkers can be processed rapidly after internalization without lysosomal delivery. Lastly, we show that sialic acid depletion enhances ADC lysosomal delivery and killing in diverse cancer cell types, including with FDA (US Food and Drug Administration)-approved trastuzumab emtansine (T-DM1) in Her2-positive breast cancer cells. Together, these results reveal new regulators of endolysosomal trafficking, provide important insights for ADC design and identify candidate combination therapy targets.

In the current value-based healthcare climate where spine surgery is shifting to the ambulatory setting, factors influencing postop length of stay (LOS) are important to surgeons and hospital administrators. Pre-op patient factors including diagnosis of radiculopathy and myelopathy have yet to be investigated in this context. Operative pts ≥ 18Y with primary diagnoses of cervical myelopathy (M), radiculopathy (R), or myeloradiculopathy (MR) were included and propensity score matched by invasiveness score (Mirza et al.). Top-quartile LOS was defined as extended. M&R patients were compared using Chi 2 & independent t-tests. Univariate tests assessed differences in preop patient and surgical data in M&R pts and extended/non-extended LOS. Stepwise regression analysis explored factors predictive of LOS. 718 operative pts (54.5 yrs, 41.1%F, 29.1 kg/m 2 , mean CCI 1.11) included (177 M, 383 R, and 158 MR). After PSM, 345 patients remained (115 in each diagnosis). 102 patients had E-LOS (Avg: 5.96 days), 41 M patients (mean 7.1 days), 28 R (5.9 days), and 33 MR (4.6 days). Regression showed predictors of E-LOS in R pts (R 2  = 0.532, p = 0.043): TS-CL, combined and posterior approach, LIV, UIV, op time, Lactated Ringer's, postoperative complications. Predictors of E-LOS in M pts (R 2  = 0.230, p < 0.001): age, CCI, combined and posterior approach, levels fused, UIV, EBL, neuro and any postop complications. Predictors of E-LOS in MR patients (R 2  = 0.152, p < 0.001): age, kyphosis, combined approach, UIV, LIV, levels fused, EBL and op time. Independent of invasiveness, patients with a primary diagnosis of myelopathy, though older aged and higher comorbidity profile, had consistently longer overall postop LOS when compared to radiculopathy or myeloradiculopathy patients., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Study Design: Retrospective study of consecutive patients at a single institution.Objective: Examine the effect of minimally invasive surgery (MIS) versus open transforaminal lumbar interbody fusion (TLIF) surgery on long-term postoperative narcotic consumption., Objective: Examine the effect of minimally invasive versus open TLIF on short-term postoperative narcotic consumption., Methods: Differences between MIS and open TLIF, including inpatient opioid and nonopioid analgesic use, discharge opioid use, and postdischarge duration of narcotic usage were compared using appropriate statistical methods., Results: A total of 172 patients (109 open; 63 MIS) underwent primary TLIF. There was no difference in baseline characteristics. The MIS TLIF cohort had a significantly shorter operative time (223 vs 251 min, P = .006) and length of stay (2.7 vs 3.7 days, P < .001) as well as less estimated blood loss (184 vs 648 mL, P < .001). MIS TLIF had significantly less total inpatient opioid usage (167 vs 255 morphine milligram equivalent [MME], P = .006) and inpatient oxycodone usage (71 vs 105 mg, P = .049). Open TLIF cases required more ongoing opiate usage at 3-month follow-up (36% open vs 21% MIS, P = .041). A subanalysis found that patients who underwent an open TLIF with a history of preoperative opioid use are significantly more likely to remain on opioids at 6-week follow-up (87% vs 65%, P = .027), 3-month follow-up (63% vs 31%, P = .008), and 6-month follow-up (50% vs 21%, P = .018) compared with MIS TLIF., Conclusion: Patients undergoing MIS TLIF required less inpatient opioids and had a decreased incidence of opioid dependence at 3-month follow-up. Patients with preoperative opioid use undergoing MIS TLIF are less likely to require long-term opioids., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Protopsaltis reports grants from DePuy Synthes, during the conduct of the study; other from Medicrea, other from NuVasive, other from Globus, other from Innovasis, other from Zimmer, and other from Cervical Spine Research Society, outside the submitted work. Dr Errico reports personal fees from K2M, other from Fastenetix, grants and personal fees from Pfizer, grants from Medtronic, other from Harms Study Group, grants from OMEGA, grants from ISSGF, and grants from Paradigm Spine, outside the submitted work. Dr Passias reports personal fees from Zimmer Biomet, personal fees from Medicrea, personal fees from Spinewave, and grants from CSRS, outside the submitted work.

The Lipid A family of glycolipids, found in the outer membranes of all Gram-negative bacteria, exhibits considerable structural diversity in both lipid and glycan moieties. The lack of facile methods to prepare analogues of these natural products represents a major roadblock in understanding the relationship between their structure and immunomodulatory activities. Here we present a modular, cell-free multienzymatic platform to access these structure-activity relationships. By individually purifying 19 Escherichia coli proteins and reconstituting them in vitro in the presence of acetyl-CoA, UDP- N-acetylglucosamine, NADPH, and ATP, we have developed a system capable of synthesizing Lipid IV A , the first bioactive intermediate in the Lipid A pathway. Our reconstituted multienzyme system revealed considerable promiscuity for orthologs with distinct substrate specificity, as illustrated by swapping enzymes from distantly related cyanobacterial and Pseudomonas species. Analysis of the agonistic and antagonistic activities of the resulting products against the THP-1 human monocytic cell line revealed hitherto unrecognized trends, while opening the door to harnessing the potent biological activities of these complex glycolipid natural products.

Study Design: Retrospective cohort study., Objective: The goals of this study were to (A) evaluate preoperative bone quality assessment and intervention practice over time and (B) review the current evidence for bone evaluation in spine fusion surgery., Summary of Background Data: Deformity spine surgery has demonstrated improved quality of life in patients; however, its cost has made it controversial. If preoperative bone quality can be optimized then potentially these treatments could be more durable; however, at present, no clinical practice guidelines have been published by professional spine surgical organizations., Methods: A retrospective cohort review was performed on patients who underwent a minimum five-level primary or revision fusion. Preoperative bone quality metrics were evaluated over time from 2012 to 2017 to find potential trends. Subgroup analysis was conducted based on age, sex, preoperative diagnosis, and spine fusion region., Results: Patient characteristics including preoperative rates of pseudarthrosis and junctional failure did not change. An increasing trend of physician bone health documentation was noted (P = 0.045) but changes in other metrics were not significant. A sex bias favored females who had higher rates of preoperative DXA studies (P = 0.001), Vitamin D 25-OH serum labs (P = 0.005), Vitamin D supplementation (P = 0.022), calcium supplementation (P < 0.001), antiresorptive therapy (P = 0.016), and surgeon clinical documentation of bone health (P = 0.008) compared with men., Conclusion: Our spine surgeons have increased documentation of bone health discussions but this has not affected bone quality interventions. A discrepancy exists favoring females over males in nearly all preoperative bone quality assessment metrics. Preoperative vitamin D level and BMD assessment should be considered in patients undergoing long fusion constructs; however, the data for bone anabolic and resorptive agents have less support. Clinical practice guidelines on preoperative bone quality assessment spine patients should be defined., Level of Evidence: 4.

Fungal highly reducing polyketide synthases (HRPKSs) biosynthesize polyketides using a single set of domains iteratively. Product release is a critical step in HRPKS function to ensure timely termination and enzyme turnover. Nearly all of the HRPKSs characterized to date employ a separate thioesterase (TE) or acyltransferase enzyme for product release. In this study, we characterized two fungal HRPKSs that have fused C-terminal TE domains, a new domain architecture for fungal HRPKSs. We showed that both HRPKS-TEs synthesize aminoacylated polyketides in an ATP-independent fashion. The KU42 TE domain selects cysteine and homocysteine and catalyzes transthioesterification using the side-chain thiol group as the nucleophile. In contrast, the KU43 TE domain selects leucine methyl ester and performs a direct amidation of the polyketide, a reaction typically catalyzed by nonribosomal peptide synthetase (NRPS) domains. The characterization of these HRPKS-TE enzymes showcases the functional diversity of HRPKS enzymes and provides potential TE domains as biocatalytic tools to diversify HRPKS structures.

Study Design: A retrospective cohort study at a single institution., Objective: The aim of this study was to analyze the perioperative and postoperative outcomes of patients who underwent open transforaminal lumbar interbody fusion (O-TLIF) and bilateral minimally invasive surgery (MIS) Wiltse approach TLIF (Wil-TLIF)., Summary of Background Data: Several studies have compared open TLIF to MIS TLIF; however, comparing the techniques using a large cohort of one-level TLIFs has not been fully explored., Methods: We reviewed the charts of patients undergoing a single-level primary posterior lumbar interbody fusion between 2012 and 2017. The cases were categorized as Open TLIF (traditional midline exposure including lateral exposure of transverse processes) or bilateral paramedian Wiltse TLIF approach. Differences between groups were assessed by t tests., Results: Two hundred twenty-seven patients underwent one-level primary TLIF (116 O-TLIF, 111 Wil-TLIF). There was no difference in age, gender, American Society of Anesthesiologists (ASA), or body mass index (BMI) between groups. Wil-TLIF had the lowest estimated blood loss (EBL; 197 vs. 499 mL O-TLIF, P ≤ 0.001), length of stay (LOS; 2.7 vs. 3.6 days O-TLIF, P ≤ 0.001), overall complication rate (12% vs. 24% O-TLIF, P = 0.015), minor complication rate (7% vs. 16% O-TLIF, P = 0.049), and 90-day readmission rate (1% vs. 8% O-TLIF, P = 0.012). Wil-TLIF was associated with the higher fluoroscopy time (83 vs. 24 seconds O-TLIF, P ≤ 0.001). There was not a significant difference in operative time, intraoperative or neurological complications, extubation time, reoperation rate, or infection rate., Conclusion: In comparing Wiltse MIS TLIF to Open TLIF, the minimally invasive paramedian Wiltse approach demonstrated the lowest EBL, LOS, readmission rates, and complications, but longer fluoroscopy times when compared with the traditional open approach., Level of Evidence: 3.