Background Genetic deletion or antagonism of the neurokinin 1 receptor (NK1R) decreases alcohol intake, alcohol reward, and stress-induced alcohol relapse in rodents, while TACR1 variation is associated with alcoholism in humans. Methods We used L822429, a specific antagonist with high affinity for the rat NK1R, and examined whether sensitivity to NK1R blockade is altered in alcohol-preferring (P) rats. Operant alcohol self-administration and progressive ratio responding were analyzed in P-rats and their founder Wistar line. We also analyzed Tacr1 expression and binding and sequenced the Tacr1 promoter from both lines. Results Systemic L822429 decreased alcohol self-administration in P-rats but did not affect the lower rates of alcohol self-administration in Wistar rats. Tacr1 expression was elevated in the prefrontal cortex and the amygdala of P-rats. In central amygdala, elevated Tacr1 expression was accompanied by elevated NK1R binding. Central amygdala (but not prefrontal cortex) infusion of L822429 replicated the systemic antagonist effects on alcohol self-administration in P-rats. All P-rats, but only 18% of their founder Wistar population, were CC homozygous for a −1372G/C single nucleotide polymorphism. In silico analysis indicated that the Tacr1 −1372 genotype could modulate binding of the transcription factors GATA-2 and E2F-1. Electromobility shift and luciferase reporter assays suggested that the −1372C allele confers increased transcription factor binding and transcription. Conclusions Genetic variation at the Tacr1 locus may contribute to elevated rates of alcohol self-administration, while at the same time increasing sensitivity to NK1R antagonist treatment.

Substance P (SP) and its cognate neurokinin-1 receptor (NK1R) are involved in alcohol-related behaviors. We have previously reported that NK1R antagonism attenuates stress-induced reinstatement of alcohol seeking and suppresses escalated alcohol self-administration, but does not affect primary reinforcement or cue-induced reinstatement. Here, we administered an NK1R antagonist or vehicle prior to footshock-induced reinstatement of alcohol seeking, and mapped the resulting neuronal activation using Fos immunohistochemistry. As expected, vehicle treated animals exposed to footshock showed induction of Fos immunoreactivity in several regions of the brain stress circuitry, including the amygdala (AMG), nucleus accumbens (NAC), dorsal raphe nucleus (DR), prefrontal cortex (PFC), and bed nucleus of the stria terminalis (BNST). NK1R antagonism selectively suppressed the stress-induced increase in Fos in the DR and NAC shell. In the DR, Fos-induction by stress largely overlapped with tryptophan hydroxylase (TrpH), indicating activation of serotonergic neurons. Of NAC shell neurons activated during stress-induced reinstatement of alcohol seeking, about 30% co-expressed dynorphin (DYN), while 70% co-expressed enkephalin (ENK). Few (<1%) activated NAC shell neurons co-expressed choline acetyltransferase (ChAT), which labels the cholinergic interneurons of this region. Infusion of the NK1R antagonist L822429 into the NAC shell blocked stress-induced reinstatement of alcohol seeking. In contrast, L822429 infusion into the DR had no effect, suggesting that the influence of NK1R signaling on neuronal activity in the DR is indirect. Taken together, our results outline a potential pathway through which endogenous NK1R activation mediates stress-induced alcohol seeking.

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Terrorist incidents that target hospitals magnify morbidity and mortality. Before a real or perceived terrorist mass casualty incident threatens a hospital and its providers, it is essential to have protocols in place to minimize damage to the infrastructure, morbidity, and mortality. In the years following the Boston Marathon bombings, much has been written about the heroic efforts of survivors and responders. Far less has been published about near misses due to lack of experience responding to a mass casualty incident resulting from terrorism. After an extensive review of the medical literature and published media in English, Spanish, and Hebrew, we were unable to identify a similar event. To the best of our knowledge, this is the first reported experience of a bomb threat caused evacuation of an emergency department in the United States while actively responding to multiple casualty terrorist incidents. We summarized the chronology of the events that led to a bomb threat being identified and the subsequent evacuation of the emergency department. We then reviewed the problematic nature of our response and described evidence-based policy changes based on data from health care, law enforcement, and counterterrorism. (Disaster Med Public Health Preparedness. 2019;13:791–798)

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Diverticulitis manifestations may cover a spectrum of mild local inflammation to diffuse feculent peritonitis. Up to 35% of patients presenting with diverticulitis will have purulent (Hinchey grade III) or feculent (Hinchey grade IV) contamination of the abdomen, with a high-associated morbidity and mortality. Surgical management may involve segmental resection with or without restoration of bowel continuity. However, emergency resection for diverticulitis can be associated with high mortality rates, as well as low stoma reversal rates at 1 year. Therefore, laparoscopic peritoneal lavage has been proposed for use in selected patients with purulent peritonitis. The topic of laparoscopic peritoneal lavage for the treatment of perforated diverticulitis in the literature has been controversial. Our review of the recent data show that laparoscopic lavage may be safe and feasible in select patients with similar rates of mortality and major morbidity. There is, however, a concern regarding an associated higher rate of postoperative abscess and early reintervention risk.

Total proctocolectomy with ileal pouch-anal anastomosis can restore gastrointestinal continuity in patients requiring colectomy for ulcerative colitis, however, it can be associated with high morbidity. Reoperation for pouch-related complications is technically challenging and often leads to deterioration of pouch function or need for permanent stoma. We report a case of acute on chronic small bowel obstruction secondary to a 360-degree twist in the small bowel introduced during creation of the ileal-anal pouch. Our novel approach at repair has not been reported in past literature which included resection and re-anastomosis of the small bowel proximal to the pouch allowing for pouch salvage with return to function.