Predictors of prolonged length of stay after elective carotid revascularization.

OBJECTIVE: Postoperative day-one discharge is used as a quality-of-care indicator after carotid revascularization. This study identifies predictors of prolonged length of stay (pLOS), defined as a postprocedural LOS of >1 day, after elective carotid revascularization. METHODS: Patients undergoing carotid endarterectomy (CEA), transcarotid artery revascularization (TCAR), and transfemoral carotid artery stenting (TFCAS) in the Vascular Quality Initiative between 2016 and 2022 were included in this analysis. Multivariable logistic regression analysis was used to identify predictors of pLOS, defined as a postprocedural LOS of >1 day, after each procedure. RESULTS: A total of 118,625 elective cases were included. pLOS was observed in nearly 23.2% of patients undergoing carotid revascularization. Major adverse events, including neurological, cardiac, infectious, and bleeding complications, occurred in 5.2% of patients and were the most significant contributor to pLOS after the three procedures. Age, female sex, non-White race, insurance status, high comorbidity index, prior ipsilateral CEA, non-ambulatory status, symptomatic presentation, surgeries occurring on Friday, and postoperative hypo- or hypertension were significantly associated with pLOS across all three procedures. For CEA, additional predictors included contralateral carotid artery occlusion, preoperative use of dual antiplatelets and anticoagulation, low physician volume (<11 cases/year), and drain use. For TCAR, preoperative anticoagulation use, low physician case volume (<6 cases/year), no protamine use, and post-stent dilatation intraoperatively were associated with pLOS. One-year analysis showed a significant association between pLOS and increased mortality for all three procedures; CEA (hazard ratio [HR],1.64; 95% confidence interval [CI], 1.49-1.82), TCAR (HR,1.56; 95% CI, 1.35-1.80), and TFCAS (HR, 1.33; 95%CI, 1.08-1.64) (all P < .05). CONCLUSIONS: A postoperative LOS of more than 1 day is not uncommon after carotid revascularization. Procedure-related complications are the most common drivers of pLOS. Identifying patients who are risk for pLOS highlights quality improvement strategies that can optimize short and 1-year outcomes of patients undergoing carotid revascularization.

A novel monobactam lacking antimicrobial activity, MC-100093, reduces sex-specific ethanol preference and depressive-like behaviors in mice.

Several ß-lactam derivatives upregulate astrocytic glutamate transporter type 1expression and are known to improve measures in models of mood and alcohol use disorders (AUD) through normalizing glutamatergic states. However, long-term, and high doses of ß-lactams may cause adverse side effects for treating mood disorders and AUD. Studies suggest that MC-100093, a novel ß-lactam lacking antimicrobial activity, rescues GLT1 expression. Thus, we sought to investigate whether MC-100093 improves affective behaviors and reduces voluntary ethanol drinking. We intraperitoneally administered MC-100093 (50 mg/kg) or vehicle once per day to C57BL/6J male and female mice (8-10 weeks old) over 6 days. We employed the open field test and the elevated plus maze to examine the effect of MC-100093 on anxiety-like behaviors. We assayed MC-100093's effects on depressive-like behaviors using the tail suspension and forced swim tests. Next, utilizing a separate cohort of male and female C57BL6 mice, we assessed the effects MC100093 treatment on voluntary ethanol drinking utilizing the 2-bottle choice continuous access drinking paradigm. After screening and selecting high-drinking mice, we systematically administered MC-100093 (50 mg/kg) or vehicle to the high-drinking mice over 6 days. Overall, we found that MC-100093 treatment resulted in sex-specific pharmacological effects with female mice displaying reduced innate depressive-like behaviors during the tail suspension and force swim testing juxtaposed with male treated mice who displayed no changes in tail suspension and a paradoxical increased depressive-like behavior during the forced swim testing. Additionally, we found that MC100093 treatment reduced female preference for 10% EtOH during the 2-bottle choice continuous access drinking with no effects of MC100093 treatment detected in male mice. Overall, this data suggests sex-specific regulation of innate depressive-like behavior and voluntary EtOH drinking by MC100093 treatment. Western blot analysis of the medial prefrontal cortex and hippocampus revealed no changes in male or female GLT1 protein abundance relative to GAPDH.

N6-substituated adenosine analog J4 attenuates anxiety-like behaviors in mice.

RATIONALE: Withdrawal from chronic alcohol exposure produces various physical and mental withdrawal symptoms. Activation of adenosine receptors is known to inhibit withdrawal-induced excitation. However, limited studies investigate how adenosine analogs may prove helpful tools to alleviate alcohol withdrawal-related affective behaviors. OBJECTIVES: This study aimed to investigate the effects of J4 compared with saline using the mice vapor or voluntary ethanol drinking model on behavioral endpoints representing ethanol-withdrawal negative emotionality commonly observed during abstinence from chronic alcohol use. METHODS: We subjected C57BL/6 J mice to chronic intermittent ethanol (CIE) exposure schedule to investigate how 72-h withdrawal from alcohol alters affective-like behavior. Next, we determined how treatment with J4, a second-generation adenosine analog, influenced affective behaviors produced by alcohol withdrawal. Finally, we determined how J4 treatment alters voluntary ethanol drinking using the two-bottle-choice drinking paradigm. RESULTS: Our results show that 72-h withdrawal from chronic intermittent ethanol exposure produces limited affective-like disturbances in male C57BL/6 J mice exposed to 4 cycles ethanol vapor. Most importantly, J4 treatment irrespective of ethanol exposure decreases innate anxiety-like behavior in mice. CONCLUSIONS: Withdrawal from chronic intermittent ethanol exposure and subsequent behavioral testing 72 h later produces minimal affective-like behavior. J4 treatment did however reduce marble-burying behavior and increased time spent in open arms of the elevated plus maze, suggesting J4 may be useful as a general anxiolytic.

Implication of Adult Hippocampal Neurogenesis in Alzheimer's Disease and Potential Therapeutic Approaches.

Alzheimer's disease is the most common neurodegenerative disease, affecting more than 6 million US citizens and representing the most prevalent cause for dementia. Neurogenesis has been repeatedly reported to be impaired in AD mouse models, but the reason for this impairment remains unclear. Several key factors play a crucial role in AD including Aß accumulation, intracellular neurofibrillary tangles accumulation, and neuronal loss (specifically in the dentate gyrus of the hippocampus). Neurofibrillary tangles have been long associated with the neuronal loss in the dentate gyrus. Of note, Aß accumulation plays an important role in the impairment of neurogenesis, but recent studies started to shed a light on the role of APP gene expression on the neurogenesis process. In this review, we will discuss the recent approaches to neurogenesis in Alzheimer disease and update the development of therapeutic methods.

Alcohol-Induced Neuroinflammatory Response and Mitochondrial Dysfunction on Aging and Alzheimer's Disease.

Mitochondria are essential organelles central to various cellular functions such as energy production, metabolic pathways, signaling transduction, lipid biogenesis, and apoptosis. In the central nervous system, neurons depend on mitochondria for energy homeostasis to maintain optimal synaptic transmission and integrity. Deficiencies in mitochondrial function, including perturbations in energy homeostasis and mitochondrial dynamics, contribute to aging, and Alzheimer's disease. Chronic and heavy alcohol use is associated with accelerated brain aging, and increased risk for dementia, especially Alzheimer's disease. Furthermore, through neuroimmune responses, including pro-inflammatory cytokines, excessive alcohol use induces mitochondrial dysfunction. The direct and indirect alcohol-induced neuroimmune responses, including pro-inflammatory cytokines, are critical for the relationship between alcohol-induced mitochondrial dysfunction. In the brain, alcohol activates microglia and increases inflammatory mediators that can impair mitochondrial energy production, dynamics, and initiate cell death pathways. Also, alcohol-induced cytokines in the peripheral organs indirectly, but synergistically exacerbate alcohol's effects on brain function. This review will provide recent and advanced findings focusing on how alcohol alters the aging process and aggravates Alzheimer's disease with a focus on mitochondrial function. Finally, we will contextualize these findings to inform clinical and therapeutic approaches towards Alzheimer's disease.