Lee JT, et al. Korean J Neurotrauma. 2024 Sep;20(3):159-167. https://doi.org/10.13004/kjnt.2024.20.e32

Lee JT, et al. Korean J Neurotrauma. 2024 Mar;20(1):69-74. https://doi.org/10.13004/kjnt.2024.20.e8

Background: The prognostic value of preoperative deterioration in older patients with moderate-to-mild traumatic brain injury (TBI) remains unclear. Therefore, this study aimed to evaluate the impact of preoperative neurological and radiological deterioration on clinical outcomes in this population undergoing surgery. Methods: We retrospectively reviewed patients aged ≥ 65 years with moderate-to-mild TBI (Glasgow Coma Scale (GCS) ≥ 9) who underwent surgery between 2013 and 2022. Patients were grouped based on preoperative deterioration, classified as neurological (≥2-point sustained GCS drop lasting more than 1 h) or radiological (new/aggravated imaging lesions). Study outcomes included in-hospital mortality and 6-month functional status. Multivariable logistic regression was performed to identify independent predictors of outcomes. Results: Among 58 patients, preoperative deterioration was observed in 34 (58.6%), including 14 (24.1%) with neurological and 20 (34.5%) with radiological deterioration. In-hospital mortality was significantly higher in patients with neurological deterioration than in those without (57.1% vs. 13.6%; p = 0.002). Radiological deterioration alone was not associated with increased mortality or unfavorable functional outcome at 6 months. Neurological deterioration was an independent predictor of in-hospital death (adjusted odds ratio (OR), 47.9; p = 0.004) and unfavorable 6-month outcome (adjusted OR, 35.0; p = 0.014), whereas radiological deterioration was not. A lower initial GCS was also associated with unfavorable outcomes (adjusted OR, 0.5; p = 0.013). Conclusions: Preoperative neurological deterioration is an independent predictor of in-hospital mortality and unfavorable functional outcome at 6 months in older patients undergoing surgery for moderate-to-mild TBI. These findings underscore clinical neurological decline—not radiologic progression—should guide prognostication and early intervention strategies.

Introduction: Background: Approximately 15% of colorectal cancers (CRC) display Microsatellite Instability (MSI) due to deficient functioning of the DNA mismatch repair (MMR) system. The origin of this deficiency is either genetic due to mutations in the MMR genes MLH1, MSH2/TACSTD1, MSH6 and PMS2 or sporadic due to hypermethylation of the promoter of the MLH1 gene (sporadic MSI). Patients diagnosed with germline mutations in MMR genes (Lynch Syndrome, LS) have an up to 70-80% lifetime risk of CRC and have the potential to benefit from effective chemopreventive strategies. In fact, the CAPP-II trial demonstrated that aspirin decreased incidence of tumors associated with LS, but barriers to its adoption are the large doses needed and the potential side effects. Use of other non-steroidal anti-inflammatory drugs (NSAID) with stronger efficacy and better tolerability may represent novel strategies for chemoprevention. Naproxen is a NSAID that is widely used with an excellent safety profile. In addition, a recent pre-clinical study sponsored by the Division of Cancer Prevention of the National Cancer Institute using a genetically engineered mouse model of Lynch Syndrome (VC-MSH2-LoxP) has shown that Naproxen is the most effective agent from a panel of NSAIDs in preventing CRC. The present clinical trial was designed to confirm, in human subjects with LS, the biomarker modulation and tolerability of Naproxen that has been observed in preclinical animal models. We report herein the background, schema and early recruitment efforts of this randomized, placebo-controlled trial.