Cardiopulmonary Bypass Suppresses Forkhead Box O3 and Downstream Autophagy in the Diabetic Human Heart.

BACKGROUND: Autophagy is an integral component of cellular homeostasis and metabolism. The exact mechanism of impaired autophagy in diabetes mellitus is unknown. Forkhead Box O3 (FOXO3α) is a key regulator of oxidative stress-related responses. We hypothesize FOXO3α is a direct upstream regulator of the autophagy pathway, and its upregulation is compromised in diabetic patients during stress of cardiopulmonary bypass (CPB). METHODS: The study enrolled 32 diabetic and 33 nondiabetic patients undergoing a cardiac surgical procedure on CPB. Right atrial tissue and serum samples were collected before and after CPB per protocol. A set of key components were quantitatively assessed and compared by microarray, immunoblotting, and immunohistochemistry studies. Data were analyzed using paired or unpaired student test. A P of <.05 or less was considered significant. RESULTS: Serum microarray showed FOXO3α was upregulated in the diabetic vs nondiabetic group after CPB (P = .033), autophagy-related 4B gene and Beclin 1 gene were greatly upregulated in the nondiabetic group (P = .028 and P = .002, respectively). On immunoblotting, there was upregulation of FOXO3α in the nondiabetic patients after CPB (P = .003). There were increased levels of Beclin-1, Bcl-2, and light chain 3B after CPB in the nondiabetic group only (P = .016, P = .005, P = .002, respectively). Sirtuin 1, Unc-51-like autophagy activating kinase 1 (ULK1), peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α), and mammalian target of rapamycin (mTOR) were not significantly changed in the nondiabetic group after CPB. CONCLUSIONS: Compared with nondiabetic patients, there was no significant upregulation of FOXO3α in diabetic patients, which could possibly explain the lack of upregulation of the autophagy process after CPB. FOXO3α could potentially serve as a therapeutic target to improve cellular homeostasis.

A Comprehensive Review of the Celiac Plexus Block for the Management of Chronic Abdominal Pain.

PURPOSE OF REVIEW: Chronic abdominal pain (CAP) is a significant health problem that can dramatically affect quality of life and survival. Pancreatic cancer is recognized as one of the most painful malignancies with 70-80% suffering from substantial pain, often unresponsive to typical medical management. Celiac plexus neurolysis and celiac plexus block (CPB) can be performed to mitigate pain through direct destruction or blockade of visceral afferent nerves. The objective of this manuscript is to provide a comprehensive review of the CPB as it pertains to CAP with a focus on the associated anatomy, indications, techniques, neurolysis/blocking agents, and complications observed in patients who undergo CPB for the treatment of CAP. RECENT FINDINGS: The CAP is difficult to manage due to lack of precision in diagnosis and limited evidence from available treatments. CAP can arise from both benign and malignant causes. Treatment options include pharmacologic, interventional, and biopsychosocial treatments. Opioid therapy is typically utilized for the treatment of CAP; however, opioid therapy is associated with multiple complications. CPB has successfully been used to treat a variety of conditions resulting in CAP. The majority of the literature specifically related to CPB is surrounding chronic pain associated with pancreatic cancer. The literature shows emerging evidence in managing CAP with CPB, specifically in pancreatic cancer. This review provides multiple aspects of CAP and CPB, including anatomy, medical necessity, indications, technical considerations, available evidence, and finally complications related to the management.

Neuropeptide Y3-36 incorporated into PVAX nanoparticle improves angiogenesis in a murine model of myocardial ischemia.

Neuropeptide-Y (NPY) leads to angiogenesis and remodeling of the ischemic myocardium. The objective of this study is to assess the therapeutic potential of NPY in a model of acute myocardial ischemia using a nanoparticles delivery system targeted to tissue with oxidative stress. NPY3-36 was loaded onto copolyoxalate containing vanillyl alcohol (PVAX) using a double emulsification strategy. Adult C57BL/J6 mice (n = 49) were randomly divided into PVAX-NPY3-36 (n = 22), Vehicle (Saline) (n = 16), and Sham (n = 11) groups. The ischemia to left anterior descending artery was induced in PVAX-NPY3-36 or vehicle groups. The tissue was collected at the end of two weeks after assessing the functional and echocardiographic data. There was a significant decrease in infarction size and mortality in PVAX-NPY3-36 group compared to the Vehicle group (P = 0.01 and P = 0.05). On echocardiography, there was significant improvement in contractility and diastolic parameters (P = 0.01). On pressure-volume loop there was significant increase in stroke volume (P = 0.01), cardiac output (P = 0.01) and ventricular stroke work (P = 0.01) in the PVAX-NPY3-36 group. On Western blot analysis, there was a significant increase in pro-angiogenic factors Ang-1, TGF-ß, PDGF- ß and its receptors and VEGF in the ischemic tissue treated with PVAX-NPY3-36 as compared to Vehicle ischemic tissue (P = 0.01, P = 0.0003, and P < 0.05 respectively). It may be possible to have targeted delivery of labile neurotransmitters NPY3-36 to the ischemic myocardium using nanoparticle PVAX and achieving angiogenesis and significant functional improvement.

Impact of left ventricular outflow tract flow acceleration on aortic valve area calculation in patients with aortic stenosis

Objective: Due to its circular shape, the area of the proximal left ventricular tract (PLVOT) adjacent to aortic valve can be derived from a single linear diameter. This is also the location of flow acceleration (FA) during systole, and pulse wave Doppler (PWD) sample volume in the PLVOT can lead to overestimation of velocity (V1) and the aortic valve area (AVA). Therefore, it is recommended to derive V1 from a region of laminar flow in the elliptical shaped distal LVOT (away from the annulus). Besides being inconsistent with the assumptions of continuity equation (CE), spatial difference in the location of flow and area measurement can result in inaccurate AVA calculation. We evaluated the impact of FA in the PLVOT on the accuracy of AVA by continuity equation (CE) in patients with aortic stenosis (AS). Methods: CE-based AVA calculations were performed in patients with AS once with PWD-derived velocity time integral (VTI) in the distal LVOT (VTILVOT) and then in the PLVOT to obtain a FA velocity profile (FA-VTILVOT) for each patient. A paired sample t-test (P < 0.05) was conducted to compare the impact of FA-VTILVOT and VTILVOT on the calculation of AVA. Result: There were 46 patients in the study. There was a 30.3% increase in the peak FA-VTILVOT as compared to the peak VTILVOT and AVA obtained by FA-VTILVOT was 29.1% higher than obtained by VTILVOT. Conclusion: Accuracy of AVA can be significantly impacted by FA in the PLVOT. LVOT area should be measured with 3D imaging in the distal LVOT.

Ultrasound-guided Intravenous Line Placement Course for Certified Registered Nurse Anesthetists: A Necessary Next Step.

Ultrasonography (US) proficiency has become a desirable skill for anesthesia providers. It is commonly used in the perioperative arena for establishing peripheral and central vascular access. Establishing intravenous access is one of the most common procedures performed by Certified Registered Nurse Anesthetists (CRNAs) as frontline anesthesia providers. However, there is no structured US training program for CRNAs for vascular access at our institution. We designed and implemented a multimodality US training program specifically for the use of surface US for central and peripheral vascular access for CRNAs. The course was conducted over 2 days and consisted of an online self-paced didactic component, integrated proctored hands-on workshops, and a posttraining examina-tion to quantify knowledge gain. Twenty-five CRNAs attended the course, with significant improvement in knowledge (pretest mean (SD) score = 59.13% (15.74%) vs posttest mean score = 70.0% (9.43%), P = .03). Two weeks after the course, each participant reported that they attempted 1.46 (1.56) ultrasound-guided vascular access procedures on average. Therefore, it is feasible to design short, focused, multimodality training programs for proficiency in the use of surface US for obtaining venous access. The CRNA's proficiency in US is likely to improve efficiency, patient experience, and safety.

Three-Dimensional Printing and Transesophageal Echocardiographic Imaging of Patient-Specific Mitral Valve Models in a Pulsatile Phantom Model.

Three-dimensional printing is increasingly used in the health care industry. Making patient-specific anatomic task trainers has been one of the more commonly described uses of this technique specifically, allowing surgeons to perform complex procedures on patient-specific models in a nonoperative setting. With regard to transesophageal echocardiography (TEE) training, commercially available simulators have been increasingly used. Even though these simulators are haptic in nature and anatomically near realistic, they lack patient specificity and the training of the dynamic workflow and imaging protocol used in the operative setting. Herein a customized pulsatile left-sided heart model that uses patient-specific 3-dimensional printed valves under physiological intracardiac pressures as a TEE task trainer is described. With this model, dynamic patient-specific valvular anatomy can be visualized with actual TEE machines by trainees to familiarize themselves with the surgery equipment and the imaging protocol.

Decreased PGC-1α Post-Cardiopulmonary Bypass Leads to Impaired Oxidative Stress in Diabetic Patients.

BACKGROUND: The mechanism of mitochondrial dysfunction after cardiopulmonary bypass (CPB) in patients with diabetes mellitus lacks understanding. We hypothesized that impaired beta-oxidation of fatty acids leads to worsened stress response in this patient population after cardiac surgery. METHODS: After Institutional Review Board approval, right atrial tissue samples were collected from 35 diabetic patients and 33 nondiabetic patients before and after CPB. Patients with glycated hemoglobin of 6.0 or greater and a clinical diagnosis of diabetes mellitus were considered to be diabetic. Immunoblotting and microarray analysis were performed to assess protein and gene expression changes. Blots were quantified with ImageJ and analyzed using one-way analysis of variance with multiple Student's t test comparisons after normalization. All p values less than 0.05 were considered significant. Immunohistochemistry was performed for cellular lipid deposition assessment. RESULTS: Diabetic patients had significantly lower levels of PGC-1α before and after CPB (p < 0.01 for both) compared with nondiabetic patients. Several upstream regulators of PGC-1α (SIRT1 and CREB) were significantly higher in nondiabetic patients before CPB (p = 0.01 and 0.0018, respectively). Antioxidant markers (NOX4 and GPX4), angiogenic factors (TGF-ß, NT3, and Ang1), and the antiapoptotic factor BCL-xL were significantly lower in diabetic patients after CPB (p < 0.05). The expression of genes supporting mitochondrial energy production (CREB5 and SLC25A40) and angiogenic genes (p < 0.05) was significantly downregulated in diabetic patients after CPB. Immunohistochemistry results showed significantly increased lipid deposition in diabetic myocardial tissue. CONCLUSIONS: Decreased PGC-1α in diabetic patients may lead to impaired mitochondrial function and attenuated antiapoptotic and angiogenic responses after CPB. Therefore, PGC-1α and upstream regulators could serve as a target for improving beta-oxidation in diabetic patients.

Training Surgical Residents for Ultrasound-Guided Assessment and Management of Unstable Patients.

OBJECTIVE: Proficiency in the use of ultrasound is presently not an ACGME required core competency for accredited surgical training. There should be a basic unified ultrasound curriculum for surgical trainees. We developed a multimodal ultrasound-training program to ensure baseline proficiency and readiness for clinical performance without impacting trainee duty hours. DESIGN: We developed and implemented a multimodal curriculum for ultrasound education and its use as a supplement to clinical evaluation of unstable patients. SETTING: A single-center study was completed in a hospital setting. PARTICIPANTS: Post-graduate year-1 surgical residents at our institution were invited to participate in a multimodal perioperative course. RESULTS: 51 residents attended the course over the three sessions. The vignette exam as a whole demonstrated a Cronbach's alpha of 0.819 indicating good internal reliability of the entire test. There was significant improvement in their knowledge in clinical vignettes (55% ±â€¯12.4 on pre-test vs. 83% ±â€¯13.2% on post-test, p<0.001). CONCLUSION: It is feasible to incorporate a focused ultrasound curriculum to assess clinically unstable patients. The multimodal nature of the course aid in the development of preclinical proficiency and decreased the orientation phase of ultrasound use.

Simulator-Based Training of Workflow in Echocardiography.

Simulator-based workflow training in echocardiography appears to be gravely lacking. Workflow, or the technical and logistical steps taken to safely and efficiently execute an ultrasound procedure, is an aspect of echocardiography nearly equivalent in importance to performing the procedure itself. A knowledge gap in workflow presently exists between trainees and senior staff; this knowledge gap stems from the fact that workflow education usually is obtained "on the job" through extended repetition. Indeed, the designers of current echocardiographic simulators have gone leaps and bounds to simulate echocardiographic procedures, but none presently allows for workflow training. In this review, the authors describe a proficiency-based educational model for echocardiography, specifically highlighting transesophageal echocardiography, and briefly discuss its design. In addition, the review describes a simulator that when used in combination with formal didactics could provide echocardiographic workflow training.