Anxiety disorders and alcohol use disorder are highly comorbid, yet identifying neural dysfunction driving comorbidity has been challenging. Lateral orbitofrontal cortex (lOFC) dysfunction has been independently observed in each disorder. Here we tested the hypothesis that the lOFC is essential to partition mechanisms for fear regulation and alcohol consumption. Specifically, the capacity to regulate fear and the propensity to consume alcohol are unrelated when lOFC is intact, but become linked through lOFC dysfunction. Male Long Evans rats received bilateral, neurotoxic lOFC lesions or sham surgery. Fear regulation was determined by establishing discrimination to danger, uncertainty, and safety cues then shifting the shock probability of the uncertainty cue. Alcohol consumption was assessed through voluntary, intermittent access to 20% ethanol. The neurotoxic lesion approach ensured lOFC dysfunction spanned testing in fear regulation and alcohol consumption. LOFC-lesioned rats demonstrated maladaptive fear generalization during probability shifts, inverting normal prediction error assignment, and subsequently consumed more alcohol. Most novel, fear regulation and alcohol consumption were inextricably linked only in lOFC-lesioned rats: extreme fear regulation predicted excessive alcohol consumption. The results reveal the lOFC is essential to partition mechanisms for fear regulation and alcohol consumption and uncover a plausible source of neural dysfunction contributing to comorbid anxiety disorders and alcohol use disorder.

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Introduction: Limited data exist on the association between blood transfusion (BT) and mortality among patients hospitalized with acute decompensated heart failure (ADHF) and anemia. There is good reason for this clinical equipoise because the benefit of enhanced oxygen delivery to tissues must be balanced with the consequences of additional volume in a hypervolemic state. The aim of this study is to determine the association between BT and short and long-term mortality among patients hospitalized with ADHF and anemia. Methods: Using EMR data from an academic referral hospital, we created a cohort of patients admitted between January 2012 and December 2019 for ADHF and anemia. Patients with ACS or transfusion dependence were excluded. BT was determined using CPT codes. Inverse probability weighting was used to balance patients who did and did not receive BT across relevant demographic, laboratory and clinical variables. We then used logistic regression and Cox proportional hazard modeling to determine the association between BT and in-hospital, 90-day, and 1-year mortality. Results: There were 2,114 patients admitted with ADHF and anemia; 490 (23%) of these patients received BT. BT was associated with 1.5-fold increased risk of in-hospital mortality (95% CI [1.05-2.16], p=0.03). Among those who survived to discharge, there was no difference in 90-day mortality (OR 1.18 [0.88-1.59], p=0.26) or 1-year mortality (OR 1.04 [0.85-1.29], p=0.69) between those who received transfusion and those who did not (Figure 1). Conclusions: Among patients admitted with ADHF and anemia, BT was associated with higher in-hospital mortality. Among those who survived to discharge, in-hospital BT was not associated with any difference in long-term mortality. Additional work is needed to understand ideal transfusion thresholds. Our work suggests the importance of judicious use of BT in patients admitted with ADHF and advises that BT is associated with a worse prognosis during admission.