Predictors of postoperative opioid use in ventral and incisional hernia repair.

BACKGROUND: One in two ventral and incisional hernia repair (VIHR) patients have preoperative opioid prescription within a year before procedure. The study's aim was to investigate risk factors of increased postoperative prescription filling in patients with or without preoperative opioid prescription. METHODS: VIHR cases from 2013 to 2017 were reviewed. State prescription drug monitoring program data were linked to patient records. The primary endpoint was cumulative opioid dose dispensed through post-discharge day 45. Morphine milligram equivalent (MME) was used for uniform comparison. RESULTS: 205 patients were included in the study (average age 53.5 years; 50.7% female). Over 35% met criteria for preoperative opioid use. Preoperative opioid tolerance, superficial wound infection, current smoking status, and any dispensed opioids within 45 days of admission were independent predictors for increased postoperative opioid utilization (p < 0.001). CONCLUSION: Preoperative opioid use during 45-day pre-admission correlated strongly with postoperative prescription filling in VIHR patients, and several independent risk factors were identified.

Apoptosis/Necroptosis Inducing Thiazole-Containing Artificial Polypeptide for Immunogenic Cell Death of Cancer.

Immunogenic cell death (ICD) has emerged as a promising approach to cancer immunotherapy. During ICD, cancer cell death and the release of damage-associated molecular pattern (DAMP) signals occur simultaneously. Increased production of reactive oxygen species (ROS) and severe endoplasmic reticulum stress are necessary for enhanced ICD. Furthermore, the levels of ROS and reduced glutathione (GSH) are involved in various cell death mechanisms. The thiazole ring structure has gained considerable interest as a functional moiety for anticancer agents. This study designed and synthesized a positively charged cell-penetrating polypeptide with a thiazole functional moiety (NS). The NS internalizes into the cancer cells through direct penetration and endo-lysosomal escape. The NS induces mitochondrial depolarization and ER stress in a concentration-dependent manner, leading to a significant ROS production and GSH depletion. Consequently, the ICD of cancer cells is activated, resulting in the release of DAMP signals. Furthermore, NS causes a shift in the cell death pathway from apoptosis to necroptosis as the concentration increases. In this study, we confirmed the possibility of NS as a promising ICD inducer that can be used while varying the concentration according to the cancer type.

Effects of the dual orexin receptor antagonist DORA-22 on sleep in 5XFAD mice.

INTRODUCTION: Sleep disruption is a characteristic of Alzheimer's disease (AD) that may exacerbate disease progression. This study tested whether a dual orexin receptor antagonist (DORA) would enhance sleep and attenuate neuropathology, neuroinflammation, and cognitive deficits in an AD-relevant mouse model, 5XFAD. METHODS: Wild-type (C57Bl6/SJL) and 5XFAD mice received chronic treatment with vehicle or DORA-22. Piezoelectric recordings monitored sleep and spatial memory was assessed via spontaneous Y-maze alternations. Aß plaques, Aß levels, and neuroinflammatory markers were measured by immunohistochemistry, enzyme-linked immunosorbent assay, and real-time polymerase chain reaction, respectively. RESULTS: In 5XFAD mice, DORA-22 significantly increased light-phase sleep without reducing Aß levels, plaque density, or neuroinflammation. Effects of DORA-22 on cognitive deficits could not be determined because the 5XFAD mice did not exhibit deficits. DISCUSSION: These findings suggest that DORAs may improve sleep in AD patients. Further investigations should optimize the dose and duration of DORA-22 treatment and explore additional AD-relevant animal models and cognitive tests.