Improvement in cardiac function and regional LV strain following intramyocardial injection of a theranostic hydrogel early postmyocardial infarction in a porcine model.

Myocardial infarction (MI) is often complicated by left ventricular (LV) remodeling and heart failure. We evaluated the feasibility of a multimodality imaging approach to guide delivery of an imageable hydrogel and assessed LV functional changes with therapy. Yorkshire pigs underwent surgical occlusions of branches of the left anterior descending and/or circumflex artery to create an anterolateral MI. We evaluated the hemodynamic and mechanical effects of intramyocardial delivery of an imageable hydrogel in the central infarct area (Hydrogel group, n = 8) and a Control group (n = 5) early post-MI. LV and aortic pressure and ECG were measured and contrast cineCT angiography was performed at baseline, 60 min post-MI, and 90 min post-hydrogel delivery. LV hemodynamic indices, pressure-volume measures, and normalized regional and global strains were measured and compared. Both Control and Hydrogel groups demonstrated a decline in heart rate, LV pressure, stroke volume, ejection fraction, and pressure-volume loop area, and an increase in myocardial performance (Tei) index and supply/demand (S/D) ratio. After hydrogel delivery, Tei index and S/D ratio were reduced to baseline levels, diastolic and systolic functional indices either stabilized or improved, and radial strain and circumferential strain increased significantly in the MI regions (ENrr: +52.7%, ENcc: +44.1%). However, the Control group demonstrated a progressive decline in all functional indices to levels significantly below those of Hydrogel group. Thus, acute intramyocardial delivery of a novel imageable hydrogel to MI region resulted in rapid stabilization or improvement in LV hemodynamics and function.NEW & NOTEWORTHY Our study demonstrates that contrast cineCT imaging can be used to evaluate the acute effects of intramyocardial delivery of a therapeutic hydrogel to the central MI region early post MI, which resulted in a rapid stabilization of LV hemodynamics and improvement in regional and global LV function.

Nuclear Cardiac Imaging in the Interventional Suite.

PURPOSE OF REVIEW: This review presents the current state of imaging approaches that enable real-time molecular imaging in the interventional suite and discusses the potential future use of integrated nuclear imaging and fluoroscopy for intraprocedural guidance in the evaluation and treatment of both cardiovascular and oncological diseases. RECENT FINDINGS: Although there are no commercially available real-time hybrid nuclear imaging devices that are approved for use in the interventional suite, prototype open gantry hybrid nuclear imaging and x-ray c-arm imaging systems and theranostic catheter for location radiotracer detection are currently undergoing development and testing by multiple groups. The integration of physiological and molecular targeted nuclear imaging for real-time delivery of targeted theranostics in the interventional laboratory may enable more personalized care for a wide variety of cardiovascular procedures and improve patient outcomes.

Early Treatment With a Single Dose of Mesenchymal Stem Cell Derived Extracellular Vesicles Modulates the Brain Transcriptome to Create Neuroprotective Changes in a Porcine Model of Traumatic Brain Injury and Hemorrhagic Shock.

BACKGROUND: Cell-based therapies using mesenchymal stem cell derived extracellular vesicles (EVs) improve neurologic outcomes in animal models of traumatic brain injury (TBI), stroke, and hemorrhage. Using a porcine 7-day survival model of TBI and hemorrhagic shock (HS), we previously demonstrated that EV-treatment was associated with reduced brain lesion size, neurologic severity score, and cerebral inflammation. However, the underlying cellular and genomic mechanisms remain poorly defined. We hypothesize that EV treatment modulates the brain transcriptome to enhance neuroprotection and neurorestoration following TBI + HS. METHODS: Swine were subjected to severe TBI (8-mm cortical impact) and HS (40% blood volume). After 1 h of shock, animals were randomized (n = 4/group) to treatment with either lactated Ringer's (LR) or LR + EV. Both groups received fluid resuscitation after 2 h of shock, and autologous packed red blood cells 5 h later.After 7-days, brains were harvested and RNA-sequencing was performed. The transcriptomic data were imported into the iPathway pipeline for bioinformatics analyses. RESULTS: 5,273 genes were differentially expressed in the LR + EV group versus LR alone (total 9,588 measured genes). Genes with the greatest upregulation were involved in synaptic transmission and neuronal development and differentiation, while downregulated genes were involved in inflammation. GO-terms experiencing the greatest modulation were involved in inflammation, brain development, and cell adhesion. Pathway analysis revealed significant modulation in the glutamatergic and GABAergic systems. Network analysis revealed downregulation of inflammation, and upregulation of neurogenesis, and neuron survival and differentiation. CONCLUSIONS: In a porcine model of TBI + HS, EV treatment was associated with an attenuation of cerebral inflammatory networks and a promotion of neurogenesis and neuroplasticity. These transcriptomic changes could explain the observed neuroprotective and neurorestorative properties associated with EV treatment.

Cecal bascule herniation through the foramen of Winslow.

Bowel obstructions can have a variety of causes, including impacted feces, adhesions, volvulus, non-internal hernias, and in rare cases internal hernias. We report a 63-year-old woman who presented to the emergency department with severe abdominal pain, nausea, vomiting, and obstructive symptoms that had started 12 hours earlier. A computed tomographic scan of the abdomen and pelvis showed a right internal hernia with a cecal bascule traversing through the foramen of Winslow, concerning for a closed-loop obstruction. The patient underwent an exploratory laparotomy with cecal bascule reduction and cecopexy. Given the increased mortality risk if undiagnosed, it is important to remain aware of internal hernias. Patient outcomes are markedly improved with early diagnosis and surgical intervention.

Acute hemorrhagic cholecystitis with gallbladder rupture and massive intra-abdominal hemorrhage.

Acute hemorrhagic cholecystitis is a rare, life-threatening condition that can be further complicated by perforation of the gallbladder. We describe a patient with clinical and radiologic findings of acute cholecystitis with a gallbladder rupture and massive intra-abdominal bleeding. Our patient is a 67-year-old male who presented with an ischemic stroke and was treated with early tissue plasminogen activator. His hospital course was complicated by a fall requiring posterior spinal fusion surgery. He recovered well, but several days later developed subxiphoid and right upper quadrant pain and an episode of hemobilia and melena. A computed tomography scan revealed an inflamed, distended gallbladder with indistinct margins and a large hematoma in the gallbladder fossa extending to the right paracolic gutter. The patient also developed hemodynamic instability concerning for hemorrhagic shock. He underwent an emergent laparoscopic converted to open subtotal fenestrating cholecystectomy with abdominal washout for management of his acute hemorrhagic cholecystitis with massive intra-abdominal hemorrhage. Prompt recognition of this lethal condition in high-risk patients is crucial for optimizing patient care.

Aerosol generation during chest compression and defibrillation in a swine cardiac arrest model.

AIM: It remains unclear whether cardiac arrest (CA) resuscitation generates aerosols that can transmit respiratory pathogens. We hypothesize that chest compression and defibrillation generate aerosols that could contain the SARS-CoV-2 virus in a swine CA model. METHODS: To simulate witnessed CA with bystander-initiated cardiopulmonary resuscitation, 3 female non-intubated swine underwent 4 min of ventricular fibrillation without chest compression or defibrillation (no-flow) followed by ten 2-min cycles of mechanical chest compression and defibrillation without ventilation. The diameter (0.3-10 µm) and quantity of aerosols generated during 45-s intervals of no-flow and chest compression before and after defibrillation were analyzed by a particle analyzer. Aerosols generated from the coughs of 4 healthy human subjects were also compared to aerosols generated by swine. RESULTS: There was no significant difference between the total aerosols generated during chest compression before defibrillation compared to no-flow. In contrast, chest compression after defibrillation generated significantly more aerosols than chest compression before defibrillation or no-flow (72.4 ±â€¯41.6 × 104 vs 12.3 ±â€¯8.3 × 104 vs 10.5 ±â€¯11.2 × 104; p < 0.05), with a shift in particle size toward larger aerosols. Two consecutive human coughs generated 54.7 ±â€¯33.9 × 104 aerosols with a size distribution smaller than post-defibrillation chest compression. CONCLUSIONS: Chest compressions alone did not cause significant aerosol generation in this swine model. However, increased aerosol generation was detected during chest compression immediately following defibrillation. Additional research is needed to elucidate the clinical significance and mechanisms by which aerosol generation during chest compression is modified by defibrillation.

Acute hemorrhagic cholecystitis with gallbladder rupture and massive intra-abdominal hemorrhage

Acute hemorrhagic cholecystitis is a rare, life-threatening condition that can be further complicated by perforation of the gallbladder. We describe a patient with clinical and radiologic findings of acute cholecystitis with a gallbladder rupture and massive intra-abdominal bleeding. Our patient is a 67-year-old male who presented with an ischemic stroke and was treated with early tissue plasminogen activator. His hospital course was complicated by a fall requiring posterior spinal fusion surgery. He recovered well, but several days later developed subxiphoid and right upper quadrant pain and an episode of hemobilia and melena. A computed tomography scan revealed an inflamed, distended gallbladder with indistinct margins and a large hematoma in the gallbladder fossa extending to the right paracolic gutter. The patient also developed hemodynamic instability concerning for hemorrhagic shock. He underwent an emergent laparoscopic converted to open subtotal fenestrating cholecystectomy with abdominal washout for management of his acute hemorrhagic cholecystitis with massive intra-abdominal hemorrhage. Prompt recognition of this lethal condition in high-risk patients is crucial for optimizing patient care.

Cecal bascule herniation through the foramen of Winslow

Bowel obstructions can have a variety of causes, including impacted feces, adhesions, volvulus, non-internal hernias, and in rare cases internal hernias. We report a 63-year-old woman who presented to the emergency department with severe abdominal pain, nausea, vomiting, and obstructive symptoms that had started 12 hours earlier. A computed tomographic scan of the abdomen and pelvis showed a right internal hernia with a cecal bascule traversing through the foramen of Winslow, concerning for a closed-loop obstruction. The patient underwent an exploratory laparotomy with cecal bascule reduction and cecopexy. Given the increased mortality risk if undiagnosed, it is important to remain aware of internal hernias. Patient outcomes are markedly improved with early diagnosis and surgical intervention.

Virtual volunteers: the importance of restructuring medical volunteering during the COVID-19 pandemic.

Healthcare systems have postponed medical volunteering services in response to the COVID-19 pandemic. However, much of the aid provided by these volunteers is crucial to patient care and hospital functioning in the American healthcare system. The adoption of online video conferencing platforms in healthcare-telehealth-offers a novel solution for volunteering during this pandemic. Virtual volunteering can alleviate pressures on medical workers, enhance patient experiences, reduce the risk of viral infection and provide a sense of normalcy for patients and families. Although further study is required, this should be an avenue considered by health systems.

Histone Deacetylase Inhibitors: A Novel Strategy for Neuroprotection and Cardioprotection Following Ischemia/Reperfusion Injury.

Ischemia/reperfusion injury is a complex molecular cascade that causes deleterious cellular damage and organ dysfunction. Stroke, sudden cardiac arrest, and acute myocardial infarction are the most common causes of ischemia/reperfusion injury without effective pharmacologic therapies. Existing preclinical evidence suggests that histone deacetylase inhibitors may be an efficacious, affordable, and clinically feasible therapy that can improve neurologic and cardiac outcomes following ischemia/reperfusion injury. In this review, we discuss the pathophysiology and epigenetic modulations of ischemia/reperfusion injury and focus on the neuroprotective and cardioprotective effects of histone deacetylase inhibitors. We also summarize the protective effects of histone deacetylase inhibitors for other vital organs and highlight the key research priorities for their successful translation to the bedside.

Early single-dose exosome treatment improves neurologic outcomes in a 7-day swine model of traumatic brain injury and hemorrhagic shock.

BACKGROUND: Early single-dose treatment with human mesenchymal stem cell-derived exosomes promotes neuroprotection and promotes blood-brain barrier integrity in models of traumatic brain injury (TBI) and hemorrhagic shock (HS) in swine. The impact of an early single dose of exosomes on late survival (7 days), however, remains unknown. We sought to evaluate the impact of early single-dose exosome treatment on neurologic outcomes, brain lesion size, inflammatory cytokines, apoptotic markers, and mediators of neural plasticity in a 7-day survival model. METHODS: Yorkshire swine were subjected to a severe TBI (8-mm cortical impact) and HS (40% estimated total blood volume). After 1 hour of shock, animals were randomized (n = 4/cohort) to receive either lactated Ringer's (5 mL) or lactated Ringer's with exosomes (1 × 10 exosome particles). After an additional hour of shock, animals were resuscitated with normal saline. Daily neurologic severity scores were compared. At 7 days following injury, lesion size, inflammatory markers, and mediators of inflammation (NF-κB), apoptosis (BAX), and neural plasticity (brain-derived neurotrophic factor) in brain tissue were compared between groups. RESULTS: Exosome-treated animals had significantly lower neurologic severity scores (first 4 days; p < 0.05) and faster neurologic recovery. At 7 days, exosome-treated animals had significantly smaller (p < 0.05) brain lesion sizes. Exosome-treated animals also had significantly lower levels of inflammatory markers (interleukin [IL]-1, IL-6, IL-8, and IL-18) and higher granulocyte-macrophage colony-stimulating factor levels compared with the control animals, indicating specific impacts on various cytokines. The BAX and NF-κB levels were significantly lower (p < 0.05) in exosome-treated animals, while brain-derived neurotrophic factor levels were significantly higher (p < 0.05) in the exosome-treated animals. CONCLUSION: In a large animal model of TBI and HS, early single-dose exosome treatment attenuates neurologic injury, decreases brain lesion size, inhibits inflammation and apoptosis, and promotes neural plasticity over a 7-day period.

Dose optimization of early high-dose valproic acid for neuroprotection in a swine cardiac arrest model.

AIM: High-dose valproic acid (VPA) improves the survival and neurologic outcomes after asphyxial cardiac arrest (CA) in rats. We characterized the pharmacokinetics, pharmacodynamics, and safety of high-dose VPA in a swine CA model to advance clinical translation. METHODS: After 8 â€‹min of untreated ventricular fibrillation CA, 20 male Yorkshire swine were resuscitated until return of spontaneous circulation (ROSC). They were block randomized to receive placebo, 75 â€‹mg/kg, 150 â€‹mg/kg, or 300 â€‹mg/kg VPA as 90-min intravenous infusion (n â€‹= â€‹5/group) beginning at ROSC. Animals were monitored for 2 additional hours then euthanized. Experimental operators were blinded to treatments. RESULTS: The mean(SD) total CA duration was 14.8(1.2) minutes. 300 â€‹mg/kg VPA animals required more adrenaline to maintain mean arterial pressure ≥80 â€‹mmHg and had worse lactic acidosis. There was a strong linear correlation between plasma free VPA Cmax and brain total VPA (r2 â€‹= â€‹0.9494; p â€‹< â€‹0.0001). VPA induced dose-dependent increases in pan- and site-specific histone H3 and H4 acetylation in the brain. Plasma free VPA Cmax is a better predictor than peripheral blood mononuclear cell histone acetylation for brain H3 and H4 acetylation (r2 â€‹= â€‹0.7189 for H3K27ac, r2 â€‹= â€‹0.7189 for pan-H3ac, and r2 â€‹= â€‹0.7554 for pan-H4ac; p â€‹< â€‹0.0001). CONCLUSIONS: Up to 150 â€‹mg/kg VPA can be safely tolerated as 90-min intravenous infusion in a swine CA model. High-dose VPA induced dose-dependent increases in brain histone H3 and H4 acetylation, which can be predicted by plasma free VPA Cmax as the pharmacodynamics biomarker for VPA target engagement after CA.