Effect of the administration route on the hemostatic efficacy of tranexamic acid in patients undergoing short-segment posterior lumbar interbody fusion: a systematic review and meta-analysis.

OBJECTIVE: Tranexamic acid (TXA) is an FDA-approved antifibrinolytic that is seeing increased popularity in spine surgery owing to its ability to reduce intraoperative blood loss (IOBL) and allogeneic transfusion requirements. The present study aimed to summarize the current literature on these formulations in the context of short-segment instrumented lumbar fusion including ≥ 1-level posterior lumbar interbody fusion (PLIF). METHODS: The PubMed, Cochrane, and Web of Science databases were queried for all full-text English studies evaluating the use of topical TXA (tTXA), systemic TXA (sTXA), or combined tTXA+sTXA in patients undergoing PLIF. The primary endpoints of interest were operative time, IOBL, and total blood loss (TBL); secondary endpoints included venous thromboembolic complication occurrence, and allogeneic and autologous transfusion requirements. Outcomes were compared using random effects. Comparisons were made between the following treatment groups: sTXA, tTXA, and sTXA+tTXA. Given that sTXA is arguably the standard of care in the literature (i.e., the most common route of administration that to this point has been studied the most), the authors compared sTXA versus tTXA and sTXA versus sTXA+tTXA. Study heterogeneity was assessed with the I2 test, and grouped analysis using the Hedge's g test was performed for measurement of effect size. RESULTS: Forty-five articles were identified, of which 17 met the criteria for inclusion with an aggregate of 1008 patients. TXA regimens included sTXA only, tTXA only, and various combinations of sTXA and tTXA. There were no significant differences in operative time, TBL, or postoperative drainage between the sTXA and tTXA groups or between the sTXA and sTXA+tTXA groups. CONCLUSIONS: The present meta-analysis suggested clinical equipoise between isolated sTXA, isolated tTXA, and combinatorial tTXA+sTXA formulations as hemostatic adjuvants/neoadjuvants in short-segment fusion including ≥ 1-level PLIF. Given the theoretically lower venous thromboembolism risk associated with tTXA, additional investigations using large cohorts comparing these two formulations within the posterior fusion population are merited. Although TXA has been shown to be effective, there are insufficient data to support topical or systemic administration as superior within the open PLIF population.

Occupational Noise Exposure in the Pediatric Dental Setting.

Purpose: To evaluate the noise levels recorded in a hospital-based pediatric dental clinic and evaluate the occupational exposure personnel have to potentially hazardous levels of noise. Methods: A SoundAdvisor™ Sound Level Meter Model 831C was used to gather 19 days of background sound data (equivalent continuous sound levels, measured as LAeq) in the open bay, quiet room, sedation suite, and operating room settings. A Spartan™ Wireless Noise Dosimeter Model 730 (Larson Davis) was utilized to capture data about personal noise exposure of pediatric dental residents over 81 clinic sessions. Personal noise exposure was compared to the Occupational Safety and Health Administration (OSHA) stand- ard. Results: Background A-weighted sound pressure level was significantly less for the open bay than in the operating room, quiet room, and oral sedation setting (P<0.05), while the operating room was significantly less than the oral sedation setting (P=0.038). Personal LAeq was significantly less for the open bay than the quiet room (P=0.007) and oral sedation settings (P=0.007). There was a significantly larger percentage of time above 80 dBA captured in the oral sedation suite compared to the open bay (P=0.010) or operating room (P=0.023). Conclusions: Daily occupational noise exposure did not exceed the thresholds set forth by OSHA. Sedation and quiet room treatment settings were noted to be the loudest pediatric dental clinical environments.

Comparison of patient-reported outcomes and clinical characteristics among patients with pituitary macroadenomas and giant adenomas.

KEY POINTS: Patients with giant adenomas are more likely to have tumor extension into the paranasal sinuses. Compared to macroadenomas, giant adenomas are not associated with worse preoperative SNOT-22 scores.

Tissue Sealant Impact on Skull Base Reconstruction Outcomes: A Systematic Review and Meta-Analysis.

OBJECTIVE: Despite significant advances in understanding of skull base reconstruction principles, the role of tissue sealants in modifying postoperative cerebrospinal fluid (CSF) leak outcomes remains controversial. We evaluate postoperative CSF leak incidence associated with tissue sealant use in skull base defect repair during endoscopic skull base surgery (ESBS). DATA SOURCES: Web of Science, PubMed/MEDLINE, Scopus, and Cochrane Library. REVIEW METHODS: Systematic review and meta-analysis of risk differences (RD). A search strategy identified original studies reporting CSF leakage following ESBS with disaggregation by tissue sealant use and/or type. RESULTS: 27 non-randomized studies (n = 2,403) were included for qualitative and meta-analysis. Reconstruction with a tissue sealant did not significantly reduce postoperative CSF leak risk compared with reconstruction without sealant (RD[95% CI] = 0.02[-0.01, 0.05]). Sub-analyses of dural sealant (-0.02[-0.11, 0.07]) and fibrin glue (0.00[-0.07, 0.07]) compared with no sealant were similarly unremarkable. Postoperative CSF leakage was not significantly modulated in further sub-analyses of DuraSeal (0.02[-0.02, 0.05]), Adherus (-0.03[-0.08, 0.03]), or Bioglue (-0.06[-0.23, 0.12]) versus no dural sealant use, or Tisseel/Tissucol versus fibrin glue nonuse (0.00[-0.05, 0.05]). No significant association was seen comparing dural sealant use versus fibrin glue use on pairwise (0.01[-0.03, 0.05]) or network meta-analysis (-0.01[-0.05, 0.04]). Limitations in source literature prevented sub-analyses stratified by leak characteristics, defect size and location, and accompanying reconstruction materials. CONCLUSION: Tissue sealant use did not appear to impact postoperative CSF leak incidence when compared with nonuse. Higher quality studies are warranted to thoroughly elucidate the clinical value of adjunct sealant use in endoscopic skull base reconstruction. LEVEL OF EVIDENCE: N/A Laryngoscope, 134:3425-3436, 2024.

Trends in Botulinum Toxin-Related Industry Payments to Physicians.

Objectives: To evaluate trends in botulinum toxin (BTX) industry payments to physicians. Methods: Cross-sectional analysis of nonroyalty, BTX-specific payments made by Allergan (Botox), Ipsen (Dysport), and Merz (Xeomin) to physicians using the 2016-2020 Open Payments Database. Results: Between 2016 and 2020, >$27 million in payments was made for BTX-related activities to dermatologists, neurologists, ophthalmologists, otolaryngologists, and plastic surgeons, with payments ranging from $3.9 million in 2016 to $8.7 million in 2019. 21.7% was paid to dermatologists, 57.5% to neurologists, 5.9% to ophthalmologists, 5.7% to otolaryngologists, and 9.1% to plastic surgeons. Conclusions: Growing amounts are being paid to physicians for BTX-related activities-both medical and aesthetic. Despite the variety of indications for BTX within otolaryngology, otolaryngology payments were overshadowed by other specialties, which may reflect greater BTX utilization in those specialties.

Risks Associated with Surgical Management of Lumbosacral Transitional Vertebrae: Systematic Review of Surgical Considerations and Illustrative Case.

BACKGROUND: Lumbosacral transitional vertebrae (LSTV) are congenital anomalies of the L5-S1 segments characterized by either sacralization of the most caudal lumbar vertebra or lumbarization of the most cephalad sacral vertebra. This variation in anatomy exposes patients to additional surgical risks. METHODS: In order to shed light on surgical considerations reported for lumbar spine cases involving LSTV as described in the extant literature, we performed a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We also present a case example in which wrong level surgery was avoided due to anatomical understanding of LSTV. RESULTS: A 48-year-old female presented with severe back pain after sustaining a fall from ten feet. The patient exhibited full motor function in all extremities but had begun to experience urinary retention. On initial imaging read, the patient was suspected to have an L1 burst fracture. A review of the imaging demonstrated a transitional vertebra. Therefore, based on the last rib corresponding to T12, the fractured level was L2. This case illustrates the risk LSTV carries for wrong site surgery; appropriate levels were then decompressed and instrumented. On systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a three database literature search identified 39 studies describing 885 patients with LSTV and relevant surgical considerations. The primary indications for surgery were for disc herniation (37%), Bertolotti's syndrome (35%), and spinal stenosis (25%). This cohort displayed a mean follow-up time of 23 months. Reherniation occurred in 12 patients (5.5%). Medical management through steroid injection was 24, 72% (n = 80) for the sample. Wrong level surgery occurred in 1.4% (n = 12) of patients. CONCLUSIONS: LSTV represents a constellation of changes in anatomy beyond just a sacralized or lumbarized vertebra. These anatomical differences expose the patient to additional surgical risks. This case and review of the literature highlight avoidable complications and in particular wrong level surgery.

The impact of nasal packing on skull base reconstruction and quality-of-life outcomes following endoscopic skull base surgery.

KEY POINTS: Nasal packing type was not associated with postoperative cerebrospinal fluid leaks Nondissolvable packing conferred an increased risk for postoperative sinonasal infections Nasal packing type did not influence short- and long-term quality-of-life scores.

Early risk assessment for Alzheimer's disease.

The purpose of the Alzheimer's Association Research Roundtable meeting was to discuss the potential of finding diagnostic tools to determine the earliest risk factors for Alzheimer's disease (AD). Currently, drugs approved for AD address symptoms which are generally manifest after the disease is already well-established, but there is a growing pipeline of drugs that may alter the underlying pathology and therefore slow or halt progression of the disease. As these drugs become available, it will become increasingly imperative that those at risk for AD be detected and possibly treated early, especially given recent indications that the disease process may start decades before the first clinical symptoms are recognized. Early detection must go hand-in-hand with qualified tools to determine the efficacy of drugs in people who may be asymptomatic or who have only very mild symptoms of the disease. Devising strategies and screening tools to identify and monitor those at risk in order to perform "prevention" trials is seen by many as a top public-health priority, made all the more urgent by an impending growth in the elderly population worldwide.

2-Cyano-3,12-dioxooleana-1,9-dien-28-imidazolide (CDDO-Im) directly targets mitochondrial glutathione to induce apoptosis in pancreatic cancer.

Surgical resection is the only curative strategy for pancreatic cancer (PC). Unfortunately, >80% of pancreatic cancer patients bear inoperable, locally advanced, chemoresistant tumors demonstrating the urgent need for development of novel therapeutic approaches to treat this disease. Here we report that the synthetic triterpenoid 2-cyano-3,12 dioxooleana-1,9 dien-28-imidazolide (CDDO-Im) antagonizes PC cell growth by inducing apoptosis at submicromolar concentrations. Notably, we demonstrate for the first time that the cytotoxicity of CDDO-Im is accompanied by the rapid and selective depletion of mitochondrial glutathione that results in accumulation of reactive oxygen species, oxidation of the cellular glutathione pool, loss of mitochondrial membrane potential, and phosphatidylserine externalization. The parent compound CDDO as well as the methyl ester of CDDO also depleted mitochondrial glutathione, demonstrating that this effect is mediated by the triterpenoid nucleus of these agents. Co-treatment with sulfhydryl nucleophiles completely prevented apoptosis and loss of viability induced by CDDO-Im, whereas alkylation of intracellular thiols by diethylmaleate or co-treatment with dithiothreitol decreased the accumulation of a biotinylated derivative of CDDO, TP-301, in PC cells, suggesting that intracellular reduced thiols are functional targets of the electrophilic triterpenoid nucleus of CDDO and its derivatives. In conclusion, our report is the first to identify mitochondrial glutathione as a target of CDDO and its derivatives and demonstrates that depletion of this antioxidant in the mitochondria is an effective strategy to induce cell death in PC cells. These results suggest that CDDO and its derivatives may offer a clinical benefit for the treatment of PC.