Effects of Concomitant CABG on Outcomes in Veterans Who Require Surgery for Endocarditis.

BACKGROUND: Infective Endocarditis (IE) is a complicated disease frequently accompanied by coronary artery disease (CAD) though no clear guidelines exist for when concomitant revascularization should be undertaken once valve surgery is indicated. Data on this topic within the United States (US) Veteran population, who have unique healthcare needs when compared to the civilian population, is sparse. We investigated the impact of concomitant coronary artery bypass grafting (CABG) on morbidity and mortality in US Veterans requiring surgical management of IE. METHODS: We identified 489 patients who underwent surgical management of IE between January 1 2010 and December 31 2020 at any of 43 Veterans Affairs (VA) cardiac surgery centers in the US. Patients were stratified based on who underwent concomitant CABG at the time of operation. Primary outcomes included the occurrence of postoperative myocardial infarction (MI), stroke, or mortality. Continuous variables were compared using independent t-tests or Mann Whitney U tests, and categorical variables were compared using the Chi square test. Cox proportional-hazard models were used to calculate risk for primary outcomes based on group. RESULTS: 61 patients (12.5%) underwent concomitant CABG for CAD. After adjusting for significant covariates, patients who underwent CABG had a higher long-term risk of MI (adjusted hazard ratios (aHR) 2.37, 95% CI: 1.29-4.35, p = 0.005) and higher risk of MI at 30-days (aHR 2.34, 95% CI: 1.06-5.19, p = 0.035). Concomitant CABG was not associated with long-term stroke or death, 30-day stroke or death, or perioperative complications. On sub-analysis of patients with moderate to severe CAD, rates of MI were higher in the CABG group at 30 days (25.9 vs. 3.4%, p = 0.016) and 1 year (33.3 vs. 3.4%, p = 0.004), though not long-term. The mean number of grafts was 1.51 ± 0.76, with only one graft performed in 65.6% (40/61) of patients. CONCLUSIONS: Concomitant CABG at the time of operation for IE was associated with increased risk of MI at 30-day and long-term, though most CABGs involved a low number of grafts. It was not associated with 30-day stroke or death, long term stroke or death, or perioperative complications. The optimal treatment of CAD noted during preoperative evaluation for veterans undergoing surgery for IE remains unclear.

Dorsal Raphe Dopamine Neurons Represent the Experience of Social Isolation.

The motivation to seek social contact may arise from either positive or negative emotional states, as social interaction can be rewarding and social isolation can be aversive. While ventral tegmental area (VTA) dopamine (DA) neurons may mediate social reward, a cellular substrate for the negative affective state of loneliness has remained elusive. Here, we identify a functional role for DA neurons in the dorsal raphe nucleus (DRN), in which we observe synaptic changes following acute social isolation. DRN DA neurons show increased activity upon social contact following isolation, revealed by in vivo calcium imaging. Optogenetic activation of DRN DA neurons increases social preference but causes place avoidance. Furthermore, these neurons are necessary for promoting rebound sociability following an acute period of isolation. Finally, the degree to which these neurons modulate behavior is predicted by social rank, together supporting a role for DRN dopamine neurons in mediating a loneliness-like state. PAPERCLIP.

A circuit mechanism for differentiating positive and negative associations.

The ability to differentiate stimuli predicting positive or negative outcomes is critical for survival, and perturbations of emotional processing underlie many psychiatric disease states. Synaptic plasticity in the basolateral amygdala complex (BLA) mediates the acquisition of associative memories, both positive and negative. Different populations of BLA neurons may encode fearful or rewarding associations, but the identifying features of these populations and the synaptic mechanisms of differentiating positive and negative emotional valence have remained unknown. Here we show that BLA neurons projecting to the nucleus accumbens (NAc projectors) or the centromedial amygdala (CeM projectors) undergo opposing synaptic changes following fear or reward conditioning. We find that photostimulation of NAc projectors supports positive reinforcement while photostimulation of CeM projectors mediates negative reinforcement. Photoinhibition of CeM projectors impairs fear conditioning and enhances reward conditioning. We characterize these functionally distinct neuronal populations by comparing their electrophysiological, morphological and genetic features. Overall, we provide a mechanistic explanation for the representation of positive and negative associations within the amygdala.