Advances in understanding the peptide neurotransmitter NAAG and appearance of a new member of the NAAG neuropeptide family.

A substantial body of data was reported between 1984 and 2000 demonstrating that the neuropeptide N-acetylaspartylglutamate (NAAG) not only functions as a neurotransmitter but also is the third most prevalent transmitter in the mammalian nervous system behind glutamate and GABA. By 2005, this conclusion was validated further through a series of studies in vivo and in vitro. The primary enzyme responsible for the inactivation of NAAG following its synaptic release had been cloned, characterized and knocked out. Potent inhibitors of this enzyme were developed and their efficacy has been extensively studied in a series of animal models of clinical conditions, including stroke, peripheral neuropathy, traumatic brain injury, inflammatory and neuropathic pain, cocaine addiction, and schizophrenia. Considerable progress also has been made in defining further the mechanism of action of these peptidase inhibitors in elevating synaptic levels of NAAG with the consequent inhibition of transmitter release via the activation of pre-synaptic metabotropic glutamate receptor 3 by this peptide. Very recent discoveries include identification of two different nervous system enzymes that mediate the synthesis of NAAG from N-acetylaspartate and glutamate and the finding that one of these enzymes also mediates the synthesis of a second member of the NAAG family of neuropeptides, N-acetylaspartylglutamylglutamate.

The impact of acute care surgery on appendicitis outcomes: Results from a national sample of university-affiliated hospitals.

BACKGROUND: Acute appendicitis is the most common indication for emergency general surgery (EGS) in the United States. We examined the role of acute care surgery (ACS) on interventions and outcomes for acute appendicitis at a national sample of university-affiliated hospitals. METHODS: We surveyed senior surgeons responsible for EGS coverage at University HealthSystems Consortium hospitals, representing more than 90% of university-affiliated hospitals in the United States. The survey elicited data on resources allocated for EGS during 2013. Responses were linked to University HealthSystems Consortium outcomes data by unique hospital identifiers. Patients treated at hospitals reporting hybrid models for EGS coverage were excluded. Differences in interventions and outcomes between patients with acute appendicitis treated at ACS hospitals versus hospitals with a general surgeon on-call model (GSOC) were analyzed using univariate comparisons and multivariable logistic regression models adjusted for patient demographics, clinical acuity, and hospital characteristics. RESULTS: We found 122 hospitals meeting criteria for analysis where 2,565 patients were treated for acute appendicitis. Forty-eight percent of hospitals had an ACS model (n = 1,414), and 52% had a GSOC model (n = 1,151). Hospitals with ACS models were more likely to treat minority patients than those with GSOC models. Patients treated at ACS hospitals were more likely to undergo laparoscopic appendectomy. In multivariable modeling of patients who had surgery (n = 2,258), patients treated at ACS hospitals had 1.86 (95% confidence interval, 1.23-2.80) greater odds of undergoing laparoscopic appendectomy. CONCLUSION: In an era when laparoscopic appendectomy is increasingly accepted for treating uncomplicated acute appendicitis, particularly in low-risk patients, it is concerning that patients treated at GSOC model hospitals are more likely to undergo traditional open surgery at the time of presentation. Furthermore, hospitals with ACS are functioning as safety-net hospitals for vulnerable patients with acute appendicitis. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Variations in the implementation of acute care surgery: results from a national survey of university-affiliated hospitals.

BACKGROUND: To date, no studies have reported nationwide adoption of acute care surgery (ACS) or identified structural and/or process variations for the care of emergency general surgery (EGS) patients within such models. METHODS: We surveyed surgeons responsible for EGS coverage at University Health Systems Consortium hospitals using an eight-page postal/e-mail questionnaire querying respondents on hospital and EGS structure/process measures. Survey responses were analyzed using descriptive statistics, univariate comparisons, and multivariable regression models. RESULTS: Of 319 potential respondents, 258 (81%) completed the surveys. A total of 81 hospitals (31%) had implemented ACS, while 134 (52%) had a traditional general surgeon on-call (GSOC) model. Thirty-eight hospitals (15%) had another model (hybrid). Larger-bed, university-based, teaching hospitals with Level 1 trauma center verification status located in urban areas were more likely to have adopted ACS. In multivariable modeling, hospital type, setting, and trauma center verification predicted ACS implementation. EGS processes of care varied, with 28% of the GSOC hospitals having block time versus 67% of the ACS hospitals (p < 0.0001), 45% of the GSOC hospitals providing ICU [intensive care unit] care to EGS patients in a surgical/trauma ICU versus 93% of the ACS hospitals (p < 0.0001), 5.7 ± 3.2 surgeons sharing call at GSOC hospitals versus 7.9 ± 2.3 surgeons at ACS hospitals (p < 0.0001), and 13% of the GSOC hospitals requiring in-house EGS call versus 75% of the ACS hospitals (p < 0.0001). Among ACS hospitals, there were variations in patient cohorting (EGS patients alone, 25%; EGS + trauma, 21%; EGS + elective, 17%; and EGS + trauma + elective, 30%), data collection (26% had prospective EGS registries), patient hand-offs (56% had attending surgeon presence), and call responsibilities (averaging 4.8 ± 1.3 calls per month, with 60% providing extra call stipend and 40% with no postcall clinical duties). CONCLUSION: The potential of the ACS on the national crisis in access to EGS care is not fully met. Variations in EGS processes of care among adopters of ACS suggest that standardized criteria for ACS implementation, much like trauma center verification criteria, may be beneficial.