History of Psychoactive Medication a Risk Factor for Neurocognitive Decline After Cardiac Surgery.

INTRODUCTION: Neurocognitive decline (NCD) is a common complication after cardiac surgery with implications for outcomes and quality of life. Identifying risk factors can help surgeons implement preventative measures, optimize modifiable risk factors, and counsel patients about risk and prognosis. METHODS: Prospective cohort study at a single academic center. 104 patients planned to undergo cardiac surgery were enrolled. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was used to measure neurocognitive function preoperatively, on postoperative day four, and postoperative day 30. NCD is defined as a change in RBANS scaled score of < -8 from baseline to postoperative day 4. Patient charts were reviewed for medication history: beta-blockers, angiotensin-converting enzyme and angiotensin receptor blockers, calcium channel blockers, statins, oral hypoglycemic agents, and psychoactive medications. Charts were also reviewed to calculate postoperative opioid usage. RESULTS: NCD was detected in 42.9% of patients. Incidence of NCD was significantly higher in patients taking a psychoactive medication (56.8%) than patients not (31.9%), P < 0.03. There was no relationship between historical use of beta-blocker, calcium-channel blocker, statin, or oral hypoglycemic medications and incidence of NCD. Simple linear regression showed no relationship between change in RBANS total scaled score and opioid usage. There was no difference in incidence of NCD at 1 mo. CONCLUSIONS: Patients with a history of taking psychoactive medications prior to cardiac surgery have an increased risk of acute postoperative NCD.

Effect of Patient Sex on Neurocognitive Decline after Cardiac Surgery.

BACKGROUND: Neurocognitive decline (NCD) is a common complication of cardiac surgery. Understanding risk factors helps surgeons counsel patients pre- and perioperatively about risk, prevention, and treatment. STUDY DESIGN: Patients undergoing cardiac surgery using cardiopulmonary bypass underwent pre- and postoperative neurocognitive testing. Neurocognitive data are presented as a change from baseline to either postoperative day 4 or to 1 month. The score is standardized with respect to age. RESULTS: Eighty-four patients underwent surgery and completed postoperative neurocognitive testing. There was no significant difference in baseline neurocognitive function. NCD was more common in female patients (71%) than male patients (26.4%) on postoperative day 4. By 1 month, the incidence of NCD is similar between female (15.0%) and male patients (14.3%). Of note, female patients differed from male patients in preoperative hematocrit, preoperative creatinine, and type of surgery. CONCLUSIONS: In the acute postoperative period, female patients are both more likely to experience NCD and experience a more severe change from baseline cognitive function. This difference between male and female patients resolves by the 1 month follow-up point. Female patients had a lower preoperative hematocrit and were more likely to receive intraoperative and perioperative blood transfusion. Lower preoperative hematocrit appears to mediate the difference in NCD between male and female patients.

Canagliflozin Improves Myocardial Perfusion, Fibrosis, and Function in a Swine Model of Chronic Myocardial Ischemia.

Background Sodium-glucose cotransporter-2 inhibitors are cardioprotective independent of glucose control, as demonstrated in animal models of acute myocardial ischemia and clinical trials. The functional and molecular mechanisms of these benefits in the setting of chronic myocardial ischemia are poorly defined. The purpose of this study is to determine the effects of canagliflozin therapy on myocardial perfusion, fibrosis, and function in a large animal model of chronic myocardial ischemia. Methods and Results Yorkshire swine underwent placement of an ameroid constrictor to the left circumflex artery to induce chronic myocardial ischemia. Two weeks later, pigs received either no drug (n=8) or 300 mg sodium-glucose cotransporter-2 inhibitor canagliflozin orally, daily (n=8). Treatment continued for 5 weeks, followed by hemodynamic measurements, harvest, and tissue analysis. Canagliflozin therapy was associated with increased stroke volume and stroke work and decreased left ventricular stiffness compared with controls. The canagliflozin group had improved perfusion to ischemic myocardium compared with controls, without differences in arteriolar or capillary density. Canagliflozin was associated with decreased interstitial and perivascular fibrosis in chronically ischemic tissue, with reduced Jak/STAT (Janus kinase/signal transducer and activator of transcription) signaling compared with controls. In ischemic myocardium of the canagliflozin group, there was increased expression and activation of adenosine monophosphate-activated protein kinase, decreased activation of endothelial nitric oxide synthase, and unchanged total endothelial nitric oxide synthase. Canagliflozin therapy reduced total protein oxidation and increased expression of mitochondrial antioxidant superoxide dismutase 2 compared with controls. Conclusions In the setting of chronic myocardial ischemia, canagliflozin therapy improves myocardial function and perfusion to ischemic territory, without changes in collateralization. Attenuation of fibrosis via reduced Jak/STAT signaling, activation of adenosine monophosphate-activated protein kinase, and antioxidant signaling may contribute to these effects.

Left Ventricular Septal Avulsion in the Setting of Blunt Cardiac Injury.

A 23-year-old man sustained blunt cardiac injury after a motor vehicle collision resulting in left ventricular septal avulsion, ruptured chordae tendineae, and moderate to severe tricuspid regurgitation that necessitated operative intervention. The patient underwent successful resection of a prolapsed avulsed septal wall segment and concomitant tricuspid valve repair.

Intratumoral delivery of antigen with complement C3-bound liposomes reduces tumor growth in mice.

Antigen presenting cells (APCs) initiate the immune response against cancer by engulfing and presenting tumor antigens to T cells. Our lab has recently developed a liposomal nanoparticle that binds complement C3 proteins, allowing it to bind to the complement C3 receptors of APCs and directly deliver antigenic peptides. APCs were shown to internalize and process complement C3-bound liposomes containing ovalbumin (OVA), resulting in a significant increase in activated T cells that recognize OVA. Mice bearing A20-OVA lymphoma tumors were treated with OVA-loaded C3-liposomes, which led to reduced tumor growth in both treated and distal tumors in all mice. Peripheral blood from treated mice had a lower percentage of immunosuppressive myeloid derived suppressor cells (MDSCs), a higher percentage of B cells, and increased anti-OVA IgG1 levels compared to control mice. These results indicate that C3-liposome delivery of tumor antigen to APCs initiates a potent and systemic antitumor immune response.