Pelvic Incidence-Lumbar Lordosis Mismatch is Not Associated with Early Reoperation for Adjacent Segment Disease after Lumbar Fusion.

STUDY DESIGN: Retrospective Cohort Study OBJECTIVES: To compare the 2-year reoperation rates for adjacent segment disease between patients with pelvic incidence-lumbar lordosis (PI-LL) mismatch postoperatively and patients with normal PI-LL measurements. METHODS: Patients undergoing elective 1-to-2 level lumbar fusion for degenerative conditions between 2016-2018 were retrospectively reviewed. Spinopelvic radiographic parameters immediately post-operation were measured and PI-LL mismatch was determined using the age-adjusted thresholds defined in Lafage et al. Following propensity score matching, early reoperation rates were compared between the PI-LL mismatch and normal PI-LL cohorts. Early reoperation was defined as symptomatic adjacent segment disease (ASD) requiring reoperation within 2 years of the index surgery. RESULTS: A total of 219 patients were identified. The average age was 59 years old with 59.8% female. The PI-LL mismatch cohort (N=148) were younger (57.5 vs. 63.5, p<0.001) and had a higher proportion of black patients (31.8% vs. 11.3%, p=0.001) compared to the normal PI-LL cohort. A total of 100 patients in the PI-LL mismatch cohort were propensity score matched to 66 patients in the normal PI-LL cohort, resulting in no difference in age (p=0.177), sex (p=0.302), race (p=0.727), or BMI (p=0.892). Using these matched cohorts, the rate of early reoperation for ASD was 8.0 % in the PI-LL mismatch cohort and 9.1% in the normal PI-LL cohort (p=0.805) with a mean time to reoperation of 1.28 and 1.33 years, respectively. CONCLUSIONS: After propensity score matching, PI-LL mismatch was not associated with early reoperation for ASD in patients undergoing 1-to-2 level lumbar fusions for degenerative conditions.

The changing epidemiology of traumatic spine injuries: a trends analysis of 26 years of patients at a major level 1 trauma center in the United States.

BACKGROUND CONTEXT: Traumatic spinal injuries (TSI) are associated with high morbidity, mortality, and resource utilization. The epidemiology of TSI varies greatly across different countries and regions and is impacted by national income levels, infrastructure, and cultural factors. Further, there may be changes over time. It is essential to investigate TSI to gain useful epidemiologic information. However, there have been no recent studies on trends for TSI in the US, despite the changing population demographics, healthcare policy, and technology. As a result, reexamination is warranted to reflect how the modern era has affected the epidemiology of US spine trauma patients and their management. PURPOSE: To determine epidemiologic trends in traumatic spine injuries over time. STUDY DESIGN/SETTING: Retrospective analysis; level 1 trauma center in the United States. PATIENT SAMPLE: A total of 21,811 patients, between the years of 1996 and 2022, who presented with traumatic spine injury. OUTCOME MEASURES: Age, sex, race, Injury Severity Score, mechanism of injury, injury diagnosis, injury level, rate of operative intervention, hospital length of stay, intensive care unit length of stay, discharge disposition, in-hospital mortality. METHODS: Data was collected from our institutional trauma registry over a 26-year period. Inclusion criteria involved at least one diagnosis of vertebral fracture, spinal cord injury, spinal subluxation, or intervertebral disc injury. Exclusion criteria consisted of patients with no diagnosed spine injury or a diagnosis of strain only. A total of 21,811 patients were included in the analysis. Descriptive statistics were tabulated and ordinary least squares linear regression was conducted for trends analysis. RESULTS: Regression analysis showed a significant upward trend in patient age (+13.83 years, ß=+0.65/year, p<.001), female sex (+2.7%, ß=+0.18%/year, p=.004), falls (+10.5%, ß=+0.82%/year, p<.001), subluxations (+12.8%, ß=+0.35%/year, p<.001), thoracic injuries (+1.5%, ß=+0.28%/year, p<.001), and discharges to subacute rehab (+15.9%, ß=+0.68%/year, p<.001). There was a significant downward trend in motor vehicle crashes (-7.8%, ß=-0.47%/year, p=.016), firearms injuries (-3.4%, ß=-0.19%/year, p<.001), sports/recreation injuries (-2.9%, ß=-0.18%/year, p<.001), spinal cord injuries (-11.25%, ß=-0.37%, p<.001), complete spinal cord injuries (-7.6%, ß=-0.24%/year, p<.001), and discharges to home (+4.5%, ß=-0.27%/year, p=.011). CONCLUSIONS: At our institution, the average spine trauma patient has trended toward older females. Falls represent an increasing proportion of the mechanism of injury, on a trajectory to become the most common cause. With time, there have been fewer spinal cord injuries and a lower proportion of complete injuries. At discharge, there has been a surge in the utilization of subacute rehabilitation facilities. Overall, there has been no significant change in injury severity, rate of operative intervention, length of stay, or mortality.

Opaganib Downregulates N-Myc Expression and Suppresses In Vitro and In Vivo Growth of Neuroblastoma Cells.

Neuroblastoma (NB), the most common cancer in infants and the most common solid tumor outside the brain in children, grows aggressively and responds poorly to current therapies. We have identified a new drug (opaganib, also known as ABC294640) that modulates sphingolipid metabolism by inhibiting the synthesis of sphingosine 1-phosphate (S1P) by sphingosine kinase-2 and elevating dihydroceramides by inhibition of dihydroceramide desaturase. The present studies sought to determine the potential therapeutic activity of opaganib in cell culture and xenograft models of NB. Cytotoxicity assays demonstrated that NB cells, including cells with amplified MYCN, are effectively killed by opaganib concentrations well below those that accumulate in tumors in vivo. Opaganib was shown to cause dose-dependent decreases in S1P and hexosylceramide levels in Neuro-2a cells, while concurrently elevating levels of dihydroceramides. As with other tumor cells, opaganib reduced c-Myc and Mcl-1 protein levels in Neuro-2a cells, and also reduced the expression of the N-Myc protein. The in vivo growth of xenografts of human SK-N-(BE)2 cells with amplified MYCN was suppressed by oral administration of opaganib at doses that are well tolerated in mice. Combining opaganib with temozolomide plus irinotecan, considered the backbone for therapy of relapsed or refractory NB, resulted in increased antitumor activity in vivo compared with temozolomide plus irinotecan or opaganib alone. Mice did not lose additional weight when opaganib was combined with temozolomide plus irinotecan, indicating that the combination is well tolerated. Opaganib has additive antitumor activity toward Neuro-2a tumors when combined with the checkpoint inhibitor anti-CTLA-4 antibody; however, the combination of opaganib with anti-PD-1 or anti-PD-L1 antibodies did not provide increased antitumor activity over that seen with opaganib alone. Overall, the data demonstrate that opaganib modulates sphingolipid metabolism and intracellular signaling in NB cells and inhibits NB tumor growth alone and in combination with other anticancer drugs. Amplified MYCN does not confer resistance to opaganib, and, in fact, the drug attenuates the expression of both c-Myc and N-Myc. The safety of opaganib has been established in clinical trials with adults with advanced cancer or severe COVID-19, and so opaganib has excellent potential for treating patients with NB, particularly in combination with temozolomide and irinotecan or anti-CTLA-4 antibody.

The Sphingolipid-Modulating Drug Opaganib Protects against Radiation-Induced Lung Inflammation and Fibrosis: Potential Uses as a Medical Countermeasure and in Cancer Radiotherapy.

Fibrosis is a chronic pathology resulting from excessive deposition of extracellular matrix components that leads to the loss of tissue function. Pulmonary fibrosis can follow a variety of diverse insults including ischemia, respiratory infection, or exposure to ionizing radiation. Consequently, treatments that attenuate the development of debilitating fibrosis are in desperate need across a range of conditions. Sphingolipid metabolism is a critical regulator of cell proliferation, apoptosis, autophagy, and pathologic inflammation, processes that are all involved in fibrosis. Opaganib (formerly ABC294640) is the first-in-class investigational drug targeting sphingolipid metabolism for the treatment of cancer and inflammatory diseases. Opaganib inhibits key enzymes in sphingolipid metabolism, including sphingosine kinase-2 and dihydroceramide desaturase, thereby reducing inflammation and promoting autophagy. Herein, we demonstrate in mouse models of lung damage following exposure to ionizing radiation that opaganib significantly improved long-term survival associated with reduced lung fibrosis, suppression of granulocyte infiltration, and reduced expression of IL-6 and TNFα at 180 days after radiation. These data further demonstrate that sphingolipid metabolism is a critical regulator of fibrogenesis, and specifically show that opaganib suppresses radiation-induced pulmonary inflammation and fibrosis. Because opaganib has demonstrated an excellent safety profile during clinical testing in other diseases (cancer and COVID-19), the present studies support additional clinical trials with this drug in patients at risk for pulmonary fibrosis.

Patients With Inflammatory Bowel Disease Are at Increased Risk of Hospitalization Due to Respiratory Syncytial Virus.

INTRODUCTION: Patients with inflammatory bowel disease (IBD) are at increased risk of developing respiratory infections. Respiratory syncytial virus (RSV) is a common respiratory virus with adverse outcomes in older adults. This study aimed to determine whether patients with IBD are at increased risk of a serious infection due to RSV. METHODS: We conducted a retrospective study using the multi-institutional research network TriNetX to assess the risk of hospitalization in a cohort of patients with IBD compared with that in a non-IBD control cohort with RSV infection from January 1, 2007, to February 27, 2023. One-to-one (1:1) propensity score matching was performed for demographic variables and RSV risk factors between the 2 cohorts. Risk was expressed as adjusted odds ratio (aOR) with 95% confidence interval (CI). RESULTS: There were 794 patients in the IBD-RSV cohort and 93,074 patients in the non-IBD-RSV cohort. The mean age of the IBD-RSV cohort was 55.6 ± 20 years, 59% were female, 80% were White, and 56.9% had Crohn's disease. The IBD-RSV cohort was at an increased risk of hospitalization (aOR 1.30, 95% CI 1.06-1.59). There was no difference in the risk (aOR 0.83, 95% CI 0.58-1.19) of a composite outcome of hospitalization-related complications between the 2 cohorts. Recent systemic corticosteroid use (<3 months) was associated with an increased risk of hospitalization (aOR 1.86, 95% CI 1.30-2.59) in the IBD-RSV cohort. DISCUSSION: We found that adult patients with IBD and RSV infection are at an increased risk of hospitalization and may benefit from the new RSV vaccine recommended for adults aged 60 years and older.

The Utility of the Validated Intraoperative Bleeding Scale in Thoracolumbar Spine Surgery: A Single-Center Prospective Study.

STUDY DESIGN: Prospective, single-center study. OBJECTIVE: To evaluate the clinical relevance of the validated intraoperative bleeding severity scale (VIBe) in thoracolumbar spine surgery. METHODS: Adult patients aged 18 through 88 undergoing elective decompression, instrumentation, and fusion of the thoracolumbar spine were prospectively enrolled after informed consent was provided and written consent was obtained. Validated intraoperative bleeding severity scores were recorded intraoperatively. Univariate analysis consisted of Student T-tests, Pearson's χ2 Tests, Fisher's Exact Tests, linear regression, and binary logistic regression. Multivariable regression was conducted to adjust for baseline characteristics and potential confounding variables. RESULTS: A total of N = 121 patients were enrolled and included in the analysis. After adjusting for confounders, VIBe scores were correlated with an increased likelihood of intraoperative blood transfusion (ß = 2.46, P = .012), postoperative blood transfusion (ß = 2.36, P = .015), any transfusion (ß = 2.49, P < .001), total transfusion volume (ß = 180.8, P = .020), and estimated blood loss (EBL) (ß = 409, P < .001). Validated intraoperative bleeding severity scores had no significant association with length of hospital stay, 30-day readmission, 30-day reoperation, 30-day emergency department visit, change in pre- to post-op hemoglobin and hematocrit, total drain output, or length of surgery. CONCLUSION: The VIBe scale is associated with perioperative transfusion rates and EBL in patients undergoing thoracolumbar spine surgery. Overall, the VIBe scale has clinically relevant meaning in spine surgery, and shows potential utility in clinical research. LEVEL OF EVIDENCE: Level II.