Racial Disparities in Surgery for Malignant Bowel Obstruction.

BACKGROUND: Operative management of patients with malignant bowel obstruction (MBO) may provide effective palliation, but is associated with substantial risks. This study aimed to analyze racial and ethnic differences in surgical outcomes for patients with MBO. METHODS: This retrospective study, using National Surgical Quality Improvement Program (NSQIP) registry data from 2010 to 2019, compared differences in outcomes by race and ethnicity for 2762 patients undergoing surgery for MBO. Multivariable logistic regression controlled for relevant covariates. RESULTS: Black patients (n = 407) had higher rates of preoperative comorbidity and were more likely than White patients (n = 2081) to have major complications (28.5% vs 21.8%; p = 0.0031), overall complications (47.4% vs 40.4%; p = 0.0087), a longer median hospital stay (12 days; interquartile range [IQR, 8-19 days] vs 10 days [IQR, 7-17 days]; p = 0.0007), and unplanned readmission (17.1% vs 12.9%; p = 0.0266). Black patients had a similar mortality rate to that of White patients and were less frequently discharged to home (67.6% vs 73.0%; p = 0.0315). Differences in morbidity between Black patients and White patients persisted after controlling for potentially confounding variables. Hispanic patients had lower mortality than White patients (6.3% vs 13.1%; p = 0.0130) and a longer hospital stay (12 days [IQR, 8-18 days] vs 10 days [IQR, 7-17 days]; p = 0.0313). Outcomes did not differ between Asian patients and White patients. CONCLUSIONS: This study demonstrated significant disparities for Black patients undergoing surgery for MBO. Understanding and addressing what drives these differences, including systemic inequalities such as access to care and racial biases, is essential to the achievement of more equitable, higher-quality patient care.

Antagonism of Sigma-1 receptor blocks heavy alcohol drinking and associated hyperalgesia in male mice.

BACKGROUND: Alcohol use disorder (AUD) is a complex psychiatric disease characterized by high alcohol intake as well as hyperkatifeia and hyperalgesia during withdrawal. A role for Sigma-1 receptors (Sig-1Rs) in the rewarding and reinforcing effects of alcohol has started to emerge in recent years, as rat studies have indicated that Sig-1R hyperactivity may result in excessive alcohol drinking. Sig-1R studies in mice are very scarce, and its potential role in alcohol-induced hyperalgesia is also unknown. METHODS: In this study, we investigated the role of Sig-1R in alcohol drinking and associated hyperalgesia in male mice, using an intermittent access 2-bottle choice model of heavy drinking. RESULTS: The Sig-1R antagonist BD-1063 was found dose dependently to reduce both alcohol intake and preference, without affecting either water or sucrose intake, suggesting that the effects are specific for alcohol. Notably, the ability of BD-1063 to suppress ethanol intake correlated with the individual baseline levels of alcohol drinking, suggesting that the treatment was more efficacious in heavy drinking animals. In addition, BD-1063 reversed alcohol-induced hyperalgesia during withdrawal, assessed using an automatic Hargreaves test, without affecting thermal sensitivity in alcohol-naïve animals or locomotor activity in either group. CONCLUSIONS: These data show that Sig-1R antagonism dose-dependently reduced ethanol consumption in heavy drinking mice as well as its efficacy in reducing alcohol-induced hyperalgesia. These findings provide a foundation for the development of novel treatments for AUD and associated pain states.

The Sigma-2 receptor / transmembrane protein 97 (σ2R/TMEM97) modulator JVW-1034 reduces heavy alcohol drinking and associated pain states in male mice.

Alcohol Use Disorder (AUD) is a chronic relapsing disorder characterized by compulsive alcohol intake, loss of control over alcohol intake, and a negative emotional state when access to alcohol is prevented. AUD is also closely tied to pain, as repeated alcohol drinking leads to increased pain sensitivity during withdrawal. The sigma-2 receptor, recently identified as transmembrane protein 97 (σ2R/TMEM97), is an integral membrane protein involved in cholesterol homeostasis and lipid metabolism. Selective σ2R/Tmem97 modulators have been recently shown to relieve mechanical hypersensitivity in animal models of neuropathic pain as well as to attenuate alcohol withdrawal signs in C. elegans and to reduce alcohol drinking in rats, suggesting a potential key role for this protein in alcohol-related behaviors. In this study, we tested the effects of a potent and selective σ2R/TMEM97 ligand, JVW-1034, on heavy alcohol drinking and alcohol-induced heightened pain states in mice using an intermittent access model. Administration of JVW-1034 decreased both ethanol intake and preference for ethanol, without affecting water intake, total fluid intake, or food intake. Notably, this effect was specific for alcohol, as JVW-1034 had no effect on sucrose intake. Furthermore, JVW-1034 reduced both thermal hyperalgesia and mechanical hypersensitivity in ethanol withdrawn mice. Our data provide important evidence that modulation of σ2R/TMEM97 with small molecules can mediate heavy alcohol drinking as well as chronic alcohol-induced heightened pain sensitivity, thereby identifying a promising novel pharmacological target for AUD and associated pain states.