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.

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.

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.