Postoperative Opioid Medication Consumption Following Single-Level Lumbar Microdiscectomy Before and After Implementation of a Multimodal Opioid-Sparing Pathway.

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.

Comparative Analysis of Inpatient Opioid Consumption Between Different Surgical Approaches Following Single Level Lumbar Spinal Fusion Surgery.

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.

Multidisciplinary conference for complex surgery leads to improved quality and safety.

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.

Clinical outcomes and proximal junctional failure in adult spinal deformity patients corrected to normative alignment versus functional alignment.

OBJECTIVE: The objective of this study was to explore the rate of proximal junctional failure (PJF) and functional outcomes of normative alignment goals compared with alignment targets based on age-appropriate physical function. METHODS: Baseline relationships between age, pelvic incidence (PI), and a component of the T1 pelvic angle (TPA) within the fusion were analyzed in adult spinal deformity (ASD) patients and compared with those of asymptomatic patients. Linear regression modeling was used to determine alignment based on PI and age in asymptomatic patients (normative alignment), and in ASD patients, alignment corresponding to age-appropriate functional status (functional alignment). A cohort of 288 ASD patients was split into two groups based on whether the patient was closer to their normative or functional alignment goal at their 6-week postoperative radiographic follow-up. The rates of proximal junctional kyphosis (PJK) and PJF were determined for each cohort. RESULTS: In the 288 ASD patients included in this pre- to postoperative analysis, there was no difference in baseline alignment or health-related quality of life (HRQOL) between the normative alignment and functional alignment groups. At 6 weeks, patients with normative alignment had a smaller TPA (4.45° vs 14.1°) and PI minus lumbar lordosis (-7.24° vs 7.4°) (both p < 0.0001) and higher PJK (40% vs 27.2%, p = 0.03) and PJF (17% vs 6.8%, p = 0.008) rates than patients with functional alignment. CONCLUSIONS: Correction in ASD patients to normative alignment resulted in higher rates of PJK and PJF without improvements in HRQOL. Correction in ASD patients to functional alignment that mirrors the physical function of their age-matched asymptomatic peers is recommended.

Clinical and Radiographic Comparison of Splinting Constructs for Distal Radius Fractures: An Effort to Free the Elbow.

OBJECTIVES: To compare short-term functional outcomes, reduction loss, and rates of surgery for distal radius fractures initially immobilized with a traditional sugar-tong splint versus clamshell splint freeing the elbow. DESIGN: Prospective randomized trial. SETTING: Level 1 trauma center. PATIENTS: Eighty-nine consecutive patients sustaining distal radius fractures were enrolled between 2018 and 2020. Short-term first follow-up (1-2 weeks) radiographic parameters and 6 weeks for functional questionnaires were established to assess initial outcomes. MAIN OUTCOME MEASURES: The main outcome measures were reduction loss based on radiographic criteria, rate of surgery, and short-term patient functional outcome using the Disabilities of the Arm, Shoulder, and Hand (DASH) score. RESULTS: There were no differences noted in DASH scores ( P -value = 0.8) or loss of reduction ( P -value = 0.69), and splint type was not correlated with likelihood to have surgery ( P = 0.22). A binomial regression model demonstrated splint type was not a significant predictor variable of loss of fracture reduction in the regression model. CONCLUSIONS: These results suggest both sugar-tong splint and clamshell splint construct are acceptable options in the acute management of distal radius fractures. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Assessing Postoperative Pseudarthrosis in Anterior Cervical Discectomy and Fusion (ACDF) on Dynamic Radiographs Using Novel Angular Measurements.

STUDY DESIGN: A retrospective review of operative patients at a single institution. OBJECTIVE: The aim was to validate a novel method of detecting pseudarthrosis on dynamic radiographs. SUMMARY OF BACKGROUND DATA: A common complication after anterior cervical discectomy and fusion is pseudarthrosis. A previously published method for detecting pseudarthrosis identifies a 1 mm difference in interspinous motion (ISM), which requires calibration of images and relies on anatomic landmarks difficult to visualize. An alternative is to use angles between spinous processes, which does not require calibration and relies on more visible landmarks. MATERIALS AND METHODS: ISM was measured on dynamic radiographs using the previously published linear method and new angular method. Angles were defined by lines from screw heads to dorsal points of spinous processes. Angular cutoff for fusion was calculated using a regression equation correlating linear and angular measures, based on the 1 mm linear cutoff. Pseudarthrosis was assessed with both cutoffs. Sensitivity, specificity, inter-reliability and intrareliability of angular and linear measures used postoperative computed tomography (CT) as the reference. RESULTS: A total of 242 fused levels (81 allograft, 84 polyetheretherketone, 40 titanium, 37 standalone cages) were measured in 143 patients (mean age 52.0±11.5, 42%F). 36 patients (66 levels) had 1-year postoperative CTs; 13 patients (13 levels) had confirmed pseudarthrosis. Linear and angular measurements closely correlated ( R =0.872), with 2.3° corresponding to 1 mm linear ISM. Potential pseudarthroses was found in 28.0% and 18.5% levels using linear and angular cutoffs, respectively. Linear cutoff had 85% sensitivity, 87% specificity; angular cutoff had 85% sensitivity, 96% specificity for detecting CT-validated pseudarthrosis. Interclass correlation coefficients were 0.974 and 0.986 (both P <0.001); intrarater reliability averaged 0.953 and 0.974 ( P <0.001 for all) for linear and angular methods, respectively. CONCLUSIONS: The angular measure for assessing potential pseudarthrosis is as sensitive as and more specific than published linear methods, has high interobserver reliability, and can be used without image calibration. LEVEL OF EVIDENCE: 3.

Incidence of dysphagia following posterior cervical spine surgery.

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%.

COVID-19 pandemic and elective spinal surgery cancelations - what happens to the patients?

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.

HuR posttranscriptionally regulates WEE1: implications for the DNA damage response in pancreatic cancer cells.

HuR (ELAV1), an RNA-binding protein abundant in cancer cells, primarily resides in the nucleus, but under specific stress (e.g., gemcitabine), HuR translocates to the cytoplasm in which it tightly modulates the expression of mRNA survival cargo. Here, we demonstrate for the first time that stressing pancreatic ductal adenocarcinoma (PDA) cells by treatment with DNA-damaging anticancer agents (mitomycin C, oxaliplatin, cisplatin, carboplatin, and a PARP inhibitor) results in HuR's translocation from the nucleus to the cytoplasm. Importantly, silencing HuR in PDA cells sensitized the cells to these agents, whereas overexpressing HuR caused resistance. HuR's role in the efficacy of DNA-damaging agents in PDA cells was, in part, attributed to the acute upregulation of WEE1 by HuR. WEE1, a mitotic inhibitor kinase, regulates the DNA damage repair pathway, and therapeutic inhibition of WEE1 in combination with chemotherapy is currently in early phase trials for the treatment of cancer. We validate WEE1 as a HuR target in vitro and in vivo by demonstrating (i) direct binding of HuR to WEE1's mRNA (a discrete 56-bp region residing in the 3' untranslated region) and (ii) HuR siRNA silencing and overexpression directly affects the protein levels of WEE1, especially after DNA damage. HuR's positive regulation of WEE1 increases γ-H2AX levels, induces Cdk1 phosphorylation, and promotes cell-cycle arrest at the G2-M transition. We describe a novel mechanism that PDA cells use to protect against DNA damage in which HuR posttranscriptionally regulates the expression and downstream function of WEE1 upon exposure to DNA-damaging agents.

Mitoxantrone targets human ubiquitin-specific peptidase 11 (USP11) and is a potent inhibitor of pancreatic cancer cell survival.

UNLABELLED: Pancreatic ductal adenocarcinoma (PDA) is the fourth leading cause of cancer-related death in the United States, with a 95% five-year mortality rate. For over a decade, gemcitabine (GEM) has been the established first-line treatment for this disease despite suboptimal response rates. The development of PARP inhibitors that target the DNA damage repair (DDR) system in PDA cells has generated encouraging results. Ubiquitin-specific peptidase 11 (USP11), an enzyme that interacts with the DDR protein BRCA2, was recently discovered to play a key role in DNA double-strand break repair and may be a novel therapeutic target. A systematic high-throughput approach was used to biochemically screen 2,000 U.S. Food and Drug Administration (FDA)-approved compounds for inhibition of USP11 enzymatic activity. Six pharmacologically active small molecules that inhibit USP11 enzymatic activity were identified. An in vitro drug sensitivity assay demonstrated that one of these USP11 inhibitors, mitoxantrone, impacted PDA cell survival with an IC50 of less than 10 nM. Importantly, across six different PDA cell lines, two with defects in the Fanconi anemia/BRCA2 pathway (Hs766T and Capan-1), mitoxantrone is 40- to 20,000-fold more potent than GEM, with increased endogenous USP11 mRNA levels associated with increased sensitivity to mitoxantrone. Interestingly, USP11 silencing in PDA cells also enhanced sensitivity to GEM. These findings establish a preclinical model for the rapid discovery of FDA-approved compounds and identify USP11 as a target of mitoxantrone in PDA. IMPLICATIONS: This high-throughput approach provides a strong rationale to study mitoxantrone in an early-phase clinical setting for the treatment of PDA.