Humanized Monoclonal Antibody Against Citrullinated Histone H3 Attenuates Myocardial Injury and Prevents Heart Failure in Rodent Models.

Excessive formation of neutrophil extracellular traps (NETs) leads to NETosis, accompanied by the release of citrullinated histone H3 (CitH3), a key mediator of septic inflammation. However, the role of CitH3 in sterile inflammation, such as acute myocardial infarction (MI) and post-MI heart failure, remains incompletely understood. We investigated the role of CitH3, a byproduct of NETosis, in myocardial ischemia/reperfusion (I/R) injury using a murine MI model.

Targeted Antioxidant Therapy Reduces Hyperglycemic Exacerbation of Myocardial Ischemia/Reperfusion Injury.

Introduction: Acute hyperglycemia (HG) enhances inflammatory and oxidative stress and exacerbates myocardial infarct size during ischemia-reperfusion injury by activating splenic leukocytes. Formyl peptide receptor 1 (FPR1) on leukocytes is activated by and mediates myocardial ischemia-reperfusion injury. We hypothesize that selective FPR1 antagonist cinnamoyl-F-(D)L-F-(D)L-F (CF) or potent reducing agent tris (2-carboxyethyl) phosphine hydrochloride (TCEP) could abrogate hyperglycemic infarct exacerbation, both alone and synergistically via a novel CF-TCEP compound that would target leukocytes for antioxidative effect.

Adenosine 2A Receptor Agonism Improves Survival in Extracorporeal Cardiopulmonary Resuscitation.

Introduction: Despite resuscitation advances including extracorporeal cardiopulmonary resuscitation (ECPR), freedom from neurologic and myocardial insult after cardiac arrest remains unlikely. We hypothesized that adenosine 2A receptor (A2AR) agonism, which attenuates reperfusion injury, would improve outcomes in a porcine model of ECPR.

Methods: Adult swine underwent 20 min of circulatory arrest followed by defibrillation and 6 h of ECPR.

Splenic monocytes mediate inflammatory response and exacerbate myocardial ischemia/reperfusion injury in a mitochondrial cell-free DNA-TLR9-NLRP3-dependent fashion.

The spleen contributes importantly to myocardial ischemia/reperfusion (MI/R) injury. Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) recruits inflammasomes, initiating inflammatory responses and mediating tissue injury. We hypothesize that myocardial cell-free DNA (cfDNA) activates the splenic NLRP3 inflammasome during early reperfusion, increases systemic inflammatory response, and exacerbates myocardial infarct.

Endoscopic Sleeve Gastroplasty: A Safe Bariatric Intervention for Class III Obesity (BMI > 40).

Purpose: Endoscopic sleeve gastroplasty (ESG) is primarily offered to patients with class I and II obesity (BMI 30-40), although there are no guidelines specifying applicability. There is little data comparing ESG to bariatric surgery in patients with class III obesity (BMI > 40). This study evaluates the short-term safety of ESG compared to sleeve gastrectomy (SG) and gastric bypass (RYGB) in patients with class III obesity.

Hydroxychloroquine Attenuates Myocardial Ischemic and Post-Ischemic Reperfusion Injury by Inhibiting the Toll-Like Receptor 9 - Type I Interferon Pathway.

Background: We hypothesized that hydroxychloroquine (HCQ) attenuates myocardial ischemia/reperfusion injury (IRI) via TLR9 - type I interferon (IFN-I) pathway inhibition.

Methods: The left coronary artery of wild-type (WT) C57BL/6 and congenic TLR9 mice was occluded for 40 minutes, with or without 60 minutes of reperfusion (40'/0' or 40'/60'). Either ODN-2088 or HCQ (TLR9 inhibitors), or ODN-1826 (TLR9 agonist) was administered to determine effect on infarct size (IS).

Topical Neck Cooling Without Systemic Hypothermia Attenuates Myocardial Ischemic Injury and Post-ischemic Reperfusion Injury.

Background: Following acute myocardial infarction (MI), irreversible damage to the myocardium can only be reduced by shortening the duration between symptom onset and revascularization. While systemic hypothermia has shown promising results in slowing pre-revascularization myocardial damage, it is resource intensive and not conducive to prehospital initiation. We hypothesized that topical neck cooling (NC), an easily implemented therapy for en route transfer to definitive therapy, could similarly attenuate myocardial ischemia-reperfusion injury (IRI).

Topical Neck Cooling Prolongs Survival of Rats with Intra-Abdominal Feculent Sepsis by Activation of the Vagus Nerve.

Global hypothermia prolongs survival in rats with intraabdominal feculent sepsis by inhibiting inflammatory responses. We hypothesized that topical neck cooling (TNC) has similar benefits. Septic shock was induced by cecal ligation and incision (CLI) in Sprague Dawley rats.

Plasmacytoid Dendritic Cells Mediate Myocardial Ischemia/Reperfusion Injury by Secreting Type I Interferons.

Background We previously demonstrated that ischemically injured cardiomyocytes release cell-free DNA and HMGB1 (high mobility group box 1 protein) into circulation during reperfusion, activating proinflammatory responses and ultimately exacerbating reperfusion injury. We hypothesize that cell-free DNA and HMGB1 mediate myocardial ischemia-reperfusion injury by stimulating plasmacytoid dendritic cells (pDCs) to secrete type I interferon (IFN-I). Methods and Results C57BL/6 and interferon alpha receptor-1 knockout mice underwent 40 minutes of left coronary artery occlusion followed by 60 minutes of reperfusion (40'/60' IR) before infarct size was evaluated by 2,3,5-Triphenyltetrazolium chloride-Blue staining.

Pulsed Ultrasound of the Spleen Prolongs Survival of Rats With Severe Intra-abdominal Sepsis.

Background: The spleen is an important contributor to the uncontrolled, excessive release of proinflammatory signals during sepsis that leads to the development of tissue injury and diffuse end-organ dysfunction. Therapeutic pulsed ultrasound (pUS) has been shown to inhibit splenic leukocyte release and reduce cytokine production in other inflammatory disease processes. We hypothesized that pUS treatment inhibits spleen-derived inflammatory responses and increases survival duration in rats with severe intra-abdominal sepsis leading to septic shock.

Therapeutic Efficacy of Alpha-Lipoic Acid against Acute Myocardial Infarction and Chronic Left Ventricular Remodeling in Mice.

Background: We hypothesized that daily administration of a potent antioxidant (-lipoic acid: ALA) would protect the heart against both acute myocardial infarction (AMI) and left ventricular remodeling (LVR) post-AMI.

Methods And Results: Two separate studies were conducted. In the AMI study, C57Bl/6 mice were fed ALA daily for 7 d prior to a 45-minute occlusion of the left coronary artery (LCA).

Pulsed ultrasound attenuates the hyperglycemic exacerbation of myocardial ischemia-reperfusion injury.

Objective: Acute hyperglycemia during myocardial infarction worsens outcomes in part by inflammatory mechanisms. Pulsed ultrasound has anti-inflammatory potential in bone healing and neuromodulation. We hypothesized that pulsed ultrasound would attenuate the hyperglycemic exacerbation of myocardial ischemia-reperfusion injury via the cholinergic anti-inflammatory pathway.

Robotic compared with laparoscopic cholecystectomy: A propensity matched analysis.

Background: As robotic surgery becomes more ubiquitous, determining clinical benefit is necessary to justify the cost and time investment required to become proficient. We hypothesized that robotic cholecystectomy would be associated with improved clinical outcomes but also increased cost as compared with standard laparoscopic cholecystectomy.

Materials And Methods: All patients undergoing robotic or laparoscopic cholecystectomy at a single academic hospital between 2007 and 2017 were identified using an institutional clinical data repository.

Adenosine 2A Receptor Activation Attenuates Ischemia Reperfusion Injury During Extracorporeal Cardiopulmonary Resuscitation.

Objective: We tested the hypothesis that systemic administration of an A2AR agonist will reduce multiorgan IRI in a porcine model of ECPR.

Summary Background Data: Advances in ECPR have decreased mortality after cardiac arrest; however, subsequent IRI contributes to late multisystem organ failure. Attenuation of IRI has been reported with the use of an A2AR agonist.

Infarct-Sparing Effect of Adenosine A2B Receptor Agonist Is Primarily Due to Its Action on Splenic Leukocytes Via a PI3K/Akt/IL-10 Pathway.

Background: Adenosine A2B receptor (AAR) agonist reduces myocardial reperfusion injury by acting on inflammatory cells. Recently, a cardiosplenic axis was shown to mediate the myocardial postischemic reperfusion injury. This study aimed to explore whether the infarct-squaring effect of AAR agonist was primarily due to its action on splenic leukocytes.

The myocardial infarct-exacerbating effect of cell-free DNA is mediated by the high-mobility group box 1-receptor for advanced glycation end products-Toll-like receptor 9 pathway.

Introduction: Damage-associated molecular patterns, such as high-mobility group box 1 (HMGB1) and cell-free DNA (cfDNA), play critical roles in mediating ischemia-reperfusion injury (IRI). HMGB1 activates RAGE to exacerbate IRI, but the mechanism underlying cfDNA-induced myocardial IRI remains unknown. We hypothesized that the infarct-exacerbating effect of cfDNA is mediated by HMGB1 and receptor for advanced glycation end products (RAGE).

Stimulation of the Beta2 Adrenergic Receptor at Reperfusion Limits Myocardial Reperfusion Injury via an Interleukin-10-Dependent Anti-Inflammatory Pathway in the Spleen.

Background: In addition to the airway-relaxing effects, β adrenergic receptor (βAR) agonists are also found to have broad anti-inflammatory effects. The current study was conducted to define the role of βAR agonists in limiting myocardial ischemia/reperfusion injury (IRI).

Methods and results: Adult male wild-type (WT) and interleukin (IL)-10 knockout (KO) mice underwent a 40-min left coronary artery ligation and 60-min reperfusion.

Inguinal hernia repair: is there a benefit to using the robot?

Background: The number of robotic surgical procedures performed yearly is constantly rising, due to improved dexterity and visualization capabilities compared with conventional methods. We hypothesized that outcomes after robotic-assisted inguinal hernia repair would not be significantly different from outcomes after laparoscopic or open repair.

Methods: All patients undergoing inguinal hernia repair between 2012 and 2016 were identified using institutional American College of Surgeons National Surgical Quality Improvement Program data.

Effect of hypothermia on splenic leukocyte modulation and survival duration in severely septic rats.

Background: Therapeutic hypothermia (HT) in severe septic shock is associated with prolonged survival. We hypothesized that moderate HT would prolong survival and modulate the inflammatory response in rats with septic shock by exerting its therapeutic effect on splenic leukocytes.

Materials And Methods: Severe septic shock was created in rats by cecal ligation and incision (CLI).

The spleen contributes importantly to myocardial infarct exacerbation during post-ischemic reperfusion in mice via signaling between cardiac HMGB1 and splenic RAGE.

The spleen plays a critical role in post-infarct myocardial remodeling. However, the role of the spleen in exacerbating myocardial infarction (MI) during acute ischemia/reperfusion (I/R) injury is unknown. The present study tests the hypothesis that splenic leukocytes are activated by substances released from ischemic myocardium to subsequently exacerbate myocardial injury during reperfusion.

Adenosine 2B Receptor Activation Reduces Myocardial Reperfusion Injury by Promoting Anti-Inflammatory Macrophages Differentiation via PI3K/Akt Pathway.

Background: Activation of the adenosine A2B receptor (A2BR) can reduce myocardial ischemia/reperfusion (IR) injury. However, the mechanism underlying the A2BR-mediated cardioprotection is less clear. The present study was designed to investigate the potential mechanisms of cardioprotection mediated by A2BR.

Splenic leukocytes mediate the hyperglycemic exacerbation of myocardial infarct size in mice.

Acute hyperglycemia during acute myocardial infarction is associated with worse myocardial injury and increased mortality. Using a mouse model of myocardial ischemia/reperfusion injury, we tested the hypothesis that acute hyperglycemia activates splenic leukocytes and subsequently exacerbates myocardial infarct size. We then examined whether the adverse effects of hyperglycemia could be attenuated by a potent anti-inflammatory agent (an agonist of the adenosine A2A receptor) administered immediately prior to reperfusion.

The infarct-sparing effect of IB-MECA against myocardial ischemia/reperfusion injury in mice is mediated by sequential activation of adenosine A3 and A 2A receptors.

Conflicting results exist regarding the role of A3 adenosine receptors (A3ARs) in mediating cardioprotection during reperfusion following myocardial infarction. We hypothesized that the effects of the A3AR agonist IB-MECA to produce cardioprotection might involve activation of other adenosine receptor subtypes. C57Bl/6 (B6), A3AR KO, A2AAR KO, and A2AAR KO/WT bone marrow chimeric mice were assigned to 12 groups undergoing either hemodynamic studies or 45 min of LAD occlusion and 60 min of reperfusion.

Atorvastatin at reperfusion reduces myocardial infarct size in mice by activating eNOS in bone marrow-derived cells.

Background: The current study was designed to test our hypothesis that atorvastatin could reduce infarct size in intact mice by activating eNOS, specifically the eNOS in bone marrow-derived cells. C57BL/6J mice (B6) and congenic eNOS knockout (KO) mice underwent 45 min LAD occlusion and 60 min reperfusion. Chimeric mice, created by bone marrow transplantation between B6 and eNOS KO mice, underwent 40 min LAD occlusion and 60 min reperfusion.

Cumulative sum: a proficiency metric for basic endoscopic training.

Background: As work hour restrictions increasingly limit some operative experiences, personalized evaluative methods are needed. We prospectively assessed the value of cumulative sum (Cusum) to measure proficiency with percutaneous endoscopic gastrostomy (PEG) among surgical trainees.

Materials And Methods: Nine postgraduate year 1 surgery residents each underwent a 1-month rotation dedicated to endoscopy.