Oxaliplatin is a widely used chemotherapy agent, but induces serious peripheral neuropathy. Duloxetine is a dual reuptake inhibitor of serotonin and norepinephrine, and is shown to be effective against pain. However, whether and how duloxetine can attenuate oxaliplatin-induced allodynia in rodents is not clearly understood. A single injection of oxaliplatin (6 mg/kg, intraperitoneal; i.p.) induced a cold and mechanical allodynia, which was assessed by acetone and von Frey filament tests, respectively. When significant allodynic signs were observed, three different doses of duloxetine (10, 30, and 60 mg/kg, i.p.) were injected. Administration of 30 and 60 mg/kg of duloxetine significantly reduced the allodynia, whereas 10 mg/kg did not. By using an in vivo extracellular recording method, we further confirmed that 30 mg/kg of duloxetine could significantly inhibit the hyperexcitability of spinal wide dynamic range (WDR) cells. The anti-allodynic effect of duloxetine was completely blocked by an intrathecal injection of phentolamine (non-selective α-adrenergic receptor antagonist, 20 μg), or prazosin (α₁-adrenergic receptor antagonists, 10 μg); however, idazoxan (α₂-adrenergic receptor antagonist, 10 μg) did not block it. In conclusion, we suggest that duloxetine may have an effective protective action against oxaliplatin-induced neuropathic pain and spinal hyperexcitability, which is mediated by spinal α₁-adrenergic receptors.

Background and Purpose: Patients with intracerebral hemorrhage (ICH) have oxidative stress. Oxidative stress contributes to the development and progression of perihematomal edema (PHE) in brain hemorrhage patients. We hypothesized that reactive oxygen species (ROS) scavengers might have a neuroprotective role in the acute period of patients with ICH. Methods: This prospective, multicenter, single-blind, randomized study was conducted between June 2017 and October 2019. Intracranial bleeding, including spontaneous ICH, secondary ICH due to vascular anomalies, venous thrombosis, neoplasms, or hemorrhagic infarction, were included in our study. These ROS scavengers were given for 14 days with a dose of N-acetylcysteine 2000 mg/d and selenium 1600 µg/d intravenously. Other patients received a placebo. The primary outcome was hemorrhage and PHE volume changes in 2-week follow-up computed tomography between ROS scavenger versus placebo groups. Results: In total, 448 patients were enrolled with 123 patients remaining after applying the inclusion and exclusion criteria. There were no significant differences in baseline characteristics between the ROS scavenger (n=57) and placebo (n=66) groups. No significant differences in baseline hematoma and PHE volumes were observed but 2 weeks follow-up computed tomography showed significant differences in PHE volume (21.90±17.63 versus 30.66±32.35, P <0.01) and PHE ratio (1.19±0.73 versus 2.05±1.27, P <0.01). Among clinical factors, time to reach target Richmond Agitation Sedation Scale (5.98 hours [95% CI, 4.82–7.241 versus 8.42 hours], [95% CI, 6.57–10.77], P <0.01) and the length of intensive care unit stays (6.46 days [95% CI, 2.38–10.55 versus 12.66 days], [95% CI, 8.47–16.85], P <0.01) were significantly shortened among patients who received ROS scavengers than among patients who did not receive ROS scavenger. Conclusions: ROS scavenger showed a significantly reduced PHE volume, time to reach target Richmond Agitation Sedation Scale, and shortened length of intensive care unit stay in patients with acute ICH. Early and high doses of ROS scavengers in a combination regimen may have played a key role in obtaining a favorable outcome in our study. Registration: URL: https://cris.nih.go.kr/cris/en ; Unique identifier: KCT0004628.

Background/Objectives: The debate continues, despite numerous studies, on whether vertebroplasty (VP) or conservative treatment is more suitable for osteoporotic vertebral compression fractures (OVCFs). Meanwhile, teriparatide (TP) has shown promise in accelerating bone healing in OVCFs. This analysis aims to clarify the potential benefits of conservative treatment using TP over VP from several clinical studies on acute OVCFs. Methods: A literature search was performed, using the MEDLINE, Embase, Cochrane Review, Web of Science, and Google Scholar databases, for studies published up until September 2023. Five studies [one randomized controlled study (RCT) and four non-RCTs] were included in a qualitative and quantitative synthesis. Data were extracted and analyzed using a random-effects model to obtain the effect size. Results: Five studies with a total of 326 (TP = 147, VP = 179) patients were included. Within the first week of treatment, the VP group showed a significantly greater decrease in their visual analog scale (VAS) scores. There was no significant difference in VAS score reduction between the two groups from one to three months. However, after 6 months, the TP group exhibited significant superiority in VAS scores and bone mineral density (BMD). Furthermore, TP was associated with a reduced number of new-onset OVCFs, with a statistically significant estimated odds ratio of 0.15 (95% CI, 0.04–0.51, p < 0.01). Conclusions: Conservative treatment using TP for acute OVCF has been found to reduce subsequent fractures, provide equivalent or superior pain control, and increase BMD compared to VP. Nonetheless, the meta-analysis results are weak, due to the low level of evidence.

OBJECTIVES: Studies have suggested that the dietary intake of antioxidant vitamins, such as vitamin C and vitamin E, has a potential role in inhibiting gastric carcinogenesis. The present study investigated the effect of antioxidant vitamins on the incidence of gastric intestinal metaplasia (GIM).METHODS: This study included 67,657 Koreans free of GIM who periodically underwent health check-ups. Dietary intake was assessed by a semiquantitative food frequency questionnaire based on the Korean National Health and Nutrition Examination Survey. Participants were categorized into 4 groups by quartiles of dietary vitamin C and vitamin E intake. The Cox proportional hazard assumption was used to determine the multivariable hazard ratio (HR) and 95% confidence interval (95% CI) for GIM.RESULTS: The third and fourth quartiles of vitamin C intake had a lower risk of GIM than the first quartile (multivariable-adjusted HR, 0.95; 95% CI, 0.88 to 1.03 in the second quartile, HR, 0.88; 95% CI, 0.81 to 0.97 in the third quartile, and HR, 0.85; 95% CI, 0.76 to 0.95 in the fourth quartile). Vitamin E intake greater than the second quartile level was significantly associated with a lower risk of GIM than the first quartile (multivariable-adjusted HR, 0.90; 95% CI, 0.82 to 0.97 in the second quartile, HR, 0.90; 95% CI, 0.82 to 0.99 in the third quartile, and HR, 0.83; 95% CI, 0.74 to 0.94 in the fourth quartile). This association was observed only in the subgroup analysis for men.CONCLUSIONS: Higher dietary intake of vitamin C and vitamin E was associated with a lower risk of GIM.

Kim M, et al. J Korean Med Sci. 2023 Apr;38(21):e161. https://doi.org/10.3346/jkms.2023.38.e161