Early Celecoxib Use in Spontaneous Intracerebral Hemorrhage is Associated with Reduced Mortality.

BACKGROUND: Hemorrhagic strokes constitute 10-15% of all strokes and have the worst mortality and morbidity of all subtypes. Mortality and morbidity of spontaneous intracerebral hemorrhage (sICH) are often secondary to the effects of inflammation, brain edema, and swelling. Studies have shown that celecoxib, a selective cyclooxygenase 2 (COX-2) inhibitor, reduces perihematomal edema formation and inflammation. This study aimed to examine the impact of celecoxib on sICH outcomes. METHODS: TriNetX, a multi-institutional research database, was retrospectively queried to identify patients with sICH. Outcomes in patients who received celecoxib within 5 days (cohort 1) were analyzed and compared to those in patients who did not receive celecoxib (cohort 2). The primary end point was mortality within 1 year of sICH. Secondary end points included ventilator dependence, tracheostomy, percutaneous endoscopic gastrostomy tube placement, craniotomy, deep venous thrombosis, pulmonary embolism, ischemic stroke, transient ischemia attack, myocardial infarction, and seizures. Further analysis was performed to assess these outcomes for patients treated with ibuprofen, a nonselective COX inhibitor. RESULTS: After propensity score matching, 833 patients were identified in each cohort based on celecoxib use. Mortality at 1 year was significantly reduced in patients with sICH receiving celecoxib compared to those who did not (13.33% vs. 17.77%; p = 0.0124). Risks of ventilator dependence, tracheostomy, percutaneous endoscopic gastrostomy tube placement, craniotomy, deep venous thrombosis, pulmonary embolism, ischemic stroke, transient ischemia attack, myocardial infarction, and seizures were not significantly increased in patients who received celecoxib within 5 days of sICH compared to those who did not receive celecoxib. There was no significant difference in mortality between patients based on ibuprofen administration. CONCLUSIONS: There exists a growing interest in using COX-2 as a potential target strategy for neuroprotection in patients with sICH, with some evidence of a mortality benefit in small cohort studies. This study shows that early celecoxib use is associated with decreased mortality in patients with sICH.

Preference Sensitive Care and Shared Decision-Making in Lumbar Spinal Stenosis: A Scoping Review.

STUDY DESIGN: Scoping review. OBJECTIVE: The objective of this study was to conduct a scoping review exploring the extent to which preference sensitivity has been studied in treatment decisions for lumbar spinal stenosis (LSS), utilizing shared decision-making (SDM) as a proxy. BACKGROUND: Preference-sensitive care involves situations where multiple treatment options exist with significant tradeoffs in cost, outcome, recovery time, and quality of life. LSS has gained research focus as a preference-sensitive care scenario. MATERIALS AND METHODS: A scoping review protocol in accordance with "Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews" regulations was registered with the Open Science Framework (ID: 9ewup) and conducted across multiple databases from January 2000 to October 2022. Study selection and characterization were performed by 3 independent reviewers and an unbiased moderator. RESULTS: The search resulted in the inclusion of 16 studies varying in design and sample size, with most published between 2016 and 2021. The studies examined variables related to SDM, patient preferences, surgeon preferences, and decision aids (DAs). The outcomes assessed included treatment choice, patient satisfaction, and patient understanding. Several studies reported that SDM influenced treatment choice and patient satisfaction, while the impact on patient understanding was less clear. DAs were used in some studies to facilitate SDM. CONCLUSION: The scoping review identified a gap in comprehensive studies analyzing the preference sensitivity of treatment for LSS and the role of DAs. Further research is needed to better understand the impact of patient preferences on treatment decisions and the effectiveness of DAs in LSS care. This review provides a foundation for future research in preference-sensitive care and SDM in the context of lumbar stenosis treatment.

Mechanics of dynamic compression plate application in fracture fixation.

BACKGROUND: Dynamic compression plating is a fundamental type of bone fracture fixation used to generate interfragmentary compression. The goal of this study was to investigate the mechanics of the surgical application of these plates, specifically how plate prebend, screw location, fracture gap, and applied torque influence the resulting compressive pressures. METHODS: Synthetic bones with transverse fractures were fixed with locking compression plates. One side of the fracture was fixed with locking screws. On the other side of the fracture, a nonlocking screw was inserted eccentrically to induce interfragmentary compression. A pressure mapping sensor within the fracture gap was used to record the resulting pressure distribution. Plate prebends of 0 mm, 1.5 mm, and 3 mm were tested. Three locations of the eccentric screw, four levels of screw torque, and two initial fracture gap conditions also were tested. FINDINGS: With increasing plate prebend, fracture compression pressures shifted significantly toward the far cortex; however, compression force decreased (P < 0.05). The 1.5 mm prebend plate resulted in the greatest contact area. Increasing screw torque generally resulted in greater fracture compression force. The introduction of a 1 mm fracture gap at the far cortex prior to dynamic compression resulted in little or no fracture compression. INTERPRETATION: The model showed that increasing plate prebend results in an increasing shift of fracture compression pressures toward the far cortex; however, this is accompanied by decreases in compressive force. Initial fracture gaps at the far cortex can result in little or no compression.

Current Trends in Total Ankle Replacement.

Ankle arthritis can result in significant pain and restriction in range of motion. Total ankle replacement (TAR) is a motion-preserving surgical option used as an alternative to total ankle arthrodesis to treat end-stage ankle arthritis. There are several generations of TAR techniques based on component design, implant material, and surgical technique. With more recent TAR implants, an attempt is made to minimize bone resection and mirror the native anatomy. There are more than 20 implant devices currently available. Implant survivorship varies among prosthesis types and generations, with improved outcomes reported with use of the more recent third- and fourth-generation ankle implants. Pre- and postoperative assessments of TAR are primarily performed by using weight-bearing radiography, with weight-bearing CT emerging as an additional imaging tool. Preoperative assessments include those of the tibiotalar angle, offset, and adjacent areas of arthritis requiring additional surgical procedures. US, nuclear medicine studies, and MRI can be used to troubleshoot complications. Effective radiologic assessment requires an understanding of the component design and corresponding normal perioperative imaging features of ankle implants, as well as recognition of common and device-specific complications. General complications seen at radiography include aseptic loosening, osteolysis, hardware subsidence, periprosthetic fracture, infection, gutter impingement, heterotopic ossification, and syndesmotic nonunion. The authors review several recent generations of TAR implants commonly used in the United States, normal pre- and postoperative imaging assessment, and imaging complications of TAR. Indications for advanced imaging of TAR are also reviewed. ©RSNA, 2023 Supplemental material is available for this article. Test Your Knowledge questions for this article are available through the Online Learning Center.

Early Celecoxib use in Patients with Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) can cause rapid brain inflammation. There is debate over the safety and efficacy of anti-inflammatory agents in its treatment. With a particular focus on cyclooxygenase 2 (COX2) selective inhibition, we sought to determine the impact of celecoxib versus no celecoxib treatment on outcomes in patients with TBI and compare these with outcomes associated with nonselective COX inhibition (ibuprofen) and corticosteroid (dexamethasone) treatment. METHODS: This retrospective cohort study used TriNetX, a large publicly available global health research network, to gather clinical data extracted from the electronic medical records. Using International Classification of Diseases, Tenth Revision and pharmacy codes, we identified patients with TBI who were and were not treated with celecoxib, ibuprofen, and dexamethasone. Analysis was performed on propensity-matched and unmatched cohorts, which were matched on demographics, comorbidities, and neurological injuries. Our primary end point was 1-year survival. Secondary end points were ventilator and tracheostomy dependence, gastrostomy tube placement, seizures, and craniotomy. RESULTS: After propensity score matching, a total of 1443 patients were identified in both the celecoxib and no celecoxib cohorts. Ninety-two (6.4%) patients in the celecoxib cohort died within 1 year following TBI versus 145 (10.0%) in the no celecoxib cohort (odds ratio 0.61; 95% confidence interval 0.46-0.80; p = 0.0003). The 1-year survival rate was 96.1% in the celecoxib cohort versus 93.1% in the no celecoxib cohort (p < 0.0001). At the end of the 1-year period, celecoxib was associated with significantly lower gastrostomy tube dependence (p = 0.017), seizure activity (p = 0.027), and myocardial infarction (p = 0.021) compared with the control cohort. Ibuprofen was also associated with higher 1-year survival probability and lower rates of post-TBI complications. Dexamethasone was broadly associated with higher morbidity but was associated with higher 1-year survival probability compared with the no dexamethasone cohort. CONCLUSIONS: Early celecoxib and ibuprofen use within 5 days post TBI was associated with higher 1-year survival probabilities and fewer complications. With emerging yet controversial preclinical evidence to suggest that COX inhibition improves TBI outcomes, this population-level study offers suggestive support for these drugs' clinical benefit, which should be pursued in prospective clinical studies.

Tumor-Derived Biomarkers in Liquid Biopsy of Glioblastoma.

There is a pressing clinical need for minimally invasive liquid biopsies to supplement imaging in the treatment of glioblastoma. Diagnostic imaging is often difficult to interpret and the medical community is divided on distinguishing among complete response, partial response, stable disease, and progressive disease. A minimally invasive liquid biopsy would supplement imaging and clinical findings and has the capacity to be helpful in several ways: 1) diagnosis, 2) selection of patients for specific treatments, 3) tracking of treatment response, and 4) prognostic value. The liquid biome is the combination of biological fluids including blood, urine, and cerebrospinal fluid that contain small amounts of tumor cells, DNA/RNA coding material, peptides, and metabolites. Within the liquid biome, 2 broad categories of biomarkers can exist: tumor-derived, which can be directly traced to the tumor, and tumor-associated, which can be traced back to the response of the body to disease. Although tumor-associated biomarkers are promising liquid biopsy candidates, recent advances in biomarker enrichment and detection have allowed concentration on a new class of biomarker: tumor-derived biomarkers. This review focuses on making the distinction between the 2 biomarker categories and highlights promising new direction.

Size-Controlled and Shelf-Stable DNA Particles for Production of Lentiviral Vectors.

Polyelectrolyte complex particles assembled from plasmid DNA (pDNA) and poly(ethylenimine) (PEI) have been widely used to produce lentiviral vectors (LVVs) for gene therapy. The current batch-mode preparation for pDNA/PEI particles presents limited reproducibility in large-scale LVV manufacturing processes, leading to challenges in tightly controlling particle stability, transfection outcomes, and LVV production yield. Here we identified the size of pDNA/PEI particles as a key determinant for a high transfection efficiency with an optimal size of 400-500 nm, due to a cellular-uptake-related mechanism. We developed a kinetics-based approach to assemble size-controlled and shelf-stable particles using preassembled nanoparticles as building blocks and demonstrated production scalability on a scale of at least 100 mL. The preservation of colloidal stability and transfection efficiency was benchmarked against particles generated using an industry standard protocol. This particle manufacturing method effectively streamlines the viral manufacturing process and improves the production quality and consistency.