Transnasal Humidified Rapid Insufflation Ventilatory Exchange in Endoscopic Esophageal Surgery.

Objectives: Transnasal humidified rapid insufflation ventilatory exchange (THRIVE) describes apneic oxygenation using humidified high flow nasal-cannula oxygen. Although it has been described as a sole mode of oxygenation in endoscopic laryngotracheal surgery, its use in endoscopic esophageal surgery under general anesthesia with neuromuscular paralysis has not previously been described. The objective of this study is to assess the safety and efficacy of THRIVE in esophagology.

Low Pressure Low Frequency Jet Ventilation: Techniques, Safety and Complications.

Objective: Manual jet ventilation is a specialized oxygenation and ventilation technique that is not available in all facilities due to lack of technical familiarity and fear of complications. The objective is to review our center's 15 year experience with low pressure low frequency jet ventilation (LPLFJV).

Methods: Retrospective review of procedures utilizing LPLFJV from 2005 to 2019 were performed collecting patient demographic, surgery type and complications.

Using NSQIP Data to Reduce Institutional Postoperative Pneumonia Rates in Non-ICU Patients: A Plan-Do-Study-Act Approach.

Background: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) is a program designed to measure and improve surgical care quality. In 2015, the study institution formed a multidisciplinary team to address the poor adult postoperative pneumonia performance (worst decile).

Study Design: The study institution is a 450+ bed tertiary care center that performs 12,000+ surgical procedures annually.

Platforms for delivery of macromolecules to sites of DNA double-strand break repair.

Double-strand break (DSB) repair foci are important therapeutic targets. Here we describe platforms for delivery of macromolecules, nanomaterials and nanomedicines to repair foci. The strategy is based on the high affinity of the human 53BP1 protein for modified chromatin present at sites of DNA damage.

Celiac Plexus Block as a Predictor of Surgical Outcome for Sympathetically Mediated Abdominal Pain in a Case of Suspected Median Arcuate Ligament Syndrome: A Case Report.

Median arcuate ligament syndrome (MALS), also known as celiac artery compression syndrome, is an uncommon condition classically characterized by chronic abdominal pain, weight loss, and abdominal bruit. Chronic mesenteric ischemia caused by intermittent compression of the celiac artery by the MAL provokes upper abdominal pain that is sympathetically mediated via the celiac plexus. Because it is a diagnosis of exclusion, diagnosis of MALS in the clinical setting is typically challenging.

Endothelin-1 contributes to the progression of renal injury in sickle cell disease via reactive oxygen species.

Background And Purpose: Endothelin-1 (ET-1) is increased in patients with sickle cell disease and may contribute to the development of sickle cell nephropathy. The current study was designed to determine whether ET-1 acting via the ETA receptor contributes to renal injury in a mouse model of sickle cell disease.

Experimental Approach: Adult, humanized HbSS (homozygous for sickle Hb) mice had increased ET-1 mRNA expression in both the cortex and the glomeruli compared with mice heterozygous for sickle and Hb A (HbAS controls).

Updated Mechanisms of Sickle Cell Disease-Associated Chronic pain.

Sickle cell disease (SCD), a hemoglobinopathy, causes sickling of red blood cells, resulting in vessel blockage, stroke, anemia, inflammation, and extreme pain. A vast majority of SCD patients experience pain on a chronic basis, and many turn to opioids to provide limited relief. The side effects that come with chronic opioid use push for research into understanding the specific mechanisms of SCD-associated chronic pain.

Receptor-mediated delivery of engineered nucleases for genome modification.

Engineered nucleases, which incise the genome at predetermined sites, have a number of laboratory and clinical applications. There is, however, a need for better methods for controlled intracellular delivery of nucleases. Here, we demonstrate a method for ligand-mediated delivery of zinc finger nucleases (ZFN) proteins using transferrin receptor-mediated endocytosis.

Thalassemia-like phenotype in a novel complex hemoglobinopathy with α, β, δ globin chain abnormalities.

The occurrence of multiple abnormalities of α, β, δ, and γ globin genes may lead to unusual and complex phenotypes when they arise simultaneously in the same individual. Here, we report the findings of an African American boy who coinherited 3 heterozygous globin gene abnormalities: the unstable β-globin chain variant; hemoglobin (Hb) Showa-Yakushiji [β110(G12) Leu→Pro], the δ-globin chain variant; HbB2 [δ16(A13) Gly→Arg] and α-thalassemia (α-thal); (α-/αα). Hb Showa-Yakushiji had been previously described in Japanese, Indian, and European populations.

Design, synthesis, and pharmacological evaluation of novel hybrid compounds to treat sickle cell disease symptoms.

A novel series of thalidomide derivatives (4a-f) designed by molecular hybridization were synthesized and evaluated in vitro and in vivo for their potential use in the oral treatment of sickle cell disease symptoms. Compounds 4a-f demonstrated analgesic, anti-inflammatory, and NO-donor properties. Compounds 4c and 4d were considered promising candidate drugs and were further evaluated in transgenic sickle cell mice to determine their capacity to reduce the levels of the proinflammatory cytokine tumor necrosis factor α (TNFα).

Pomalidomide augments fetal hemoglobin production without the myelosuppressive effects of hydroxyurea in transgenic sickle cell mice.

Pharmacologic induction of fetal hemoglobin (HbF) expression is an effective treatment strategy for sickle cell disease (SCD) and β-thalassemia. Pomalidomide is a potent structural analog of thalidomide and member of a new class of immunomodulatory drugs. Recent reports demonstrated that pomalidomide reduced or eliminated transfusion requirements in certain hematologic malignancies and induced HbF ex vivo in CD34(+) progenitor cells from healthy and SCD donors.

Attenuation of hematoma size and neurological injury with curcumin following intracerebral hemorrhage in mice.

Object: Intracerebral hemorrhage (ICH) is associated with significant morbidity and mortality. Acute hematoma enlargement is an important predictor of neurological injury and poor clinical prognosis; but neurosurgical clot evacuation may not be feasible in all patients and treatment options remain largely supportive. Thus, novel therapeutic approaches to promote hematoma resolution are needed.

Curcumin attenuates cerebral edema following traumatic brain injury in mice: a possible role for aquaporin-4?

Traumatic brain injury is a devastating neurological injury associated with significant morbidity and mortality. Medical therapies to limit cerebral edema, a cause of increased intracranial hypertension and poor clinical outcome, are largely ineffective, emphasizing the need for novel therapeutic approaches. In the present study, pre-treatment with curcumin (75, 150 mg/kg) or 30 min post-treatment with 300 mg/kg significantly reduced brain water content and improved neurological outcome following a moderate controlled cortical impact in mice.

Long-term outcome after anesthesia and surgery: remarks on the biology of a newly emerging principle in perioperative care.

There is a strong possibility that the risk from anesthesia and surgery carries over from the immediate perioperative period to more remote time points. This extended risk seems to influence the progression, severity, and complication rate of certain chronic illnesses, such as vascular heart disease and some of the malignancies, although other disease processes might be affected as well. With the recognition that the perioperative process could be responsible for later adverse events comes the need to reassess existing patient safety models, because some of the risk could be preventable.

Anesthesia drugs, immunity, and long-term outcome.

Purpose Of Review: We provide an overview of the immunological effects of commonly used anesthetic drugs and highlight their potential impact on long-term outcome after surgery.

Recent Findings: Clinical trials provide preliminary evidence that the perioperative process can influence long-term patient outcome. Immunology may begin to elucidate the biology of this safety concern and open new therapeutic opportunities.

The diabetic surgical patient.

Purpose Of Review: This review summarizes the current progress in disease classification, pathophysiology and management of diabetes mellitus with a special focus on treatment modalities and recommendations for the practicing anesthesiologist.

Recent Findings: The revised classification of diabetes mellitus emphasizes disease cause and eliminates any reference to age-of-onset and insulin therapy. Hyperglycemia has emerged as an important marker of outcome in the operating room.

Fas-associated death-domain protein inhibits TNF-alpha mediated NF-kappaB activation in cardiomyocytes.

Fas-associated death-domain protein (FADD) is an adaptor molecule that links death receptors to caspase-8 in many cell types including cardiomyocytes (CMs). Although FADD has previously been reported to play an important role in CM apoptosis, the effect of FADD on CM NF-kappaB signaling, which is a proinflammatory pathway, has not been delineated. To investigate the role of FADD in CM NF-kappaB activation, we utilized adenoviral gene transfer of wild-type FADD and a truncation mutant that lacks the death-effector domain (FADD-DED) in rat CMs in vitro TNF-alpha activated NF-kappaB in CMs as demonstrated by phosphorylation and degradation of inhibitory-kappaB (IkappaB)-alpha-enhanced nuclear p65 and NF-kappaB DNA-binding activity as well as increased mRNA for the NF-kappaB-dependent adhesion molecule VCAM-1 (19 +/- 4.

Endothelial IKK beta signaling is required for monocyte adhesion under laminar flow conditions.

Endothelial activation induces expression of pro-inflammatory molecules that are thought to play an important role in atherogenesis through enhanced vascular monocyte recruitment. Many pro-inflammatory endothelial signals are transcriptionally regulated by members of the NF- kappa B family. The serine-threonine kinase, IKK beta, can mediate NF- kappa B activation although several alternative pathways exist.

Cardiomyopathy in zebrafish due to mutation in an alternatively spliced exon of titin.

The zebrafish embryo is transparent and can tolerate absence of blood flow because its oxygen is delivered by diffusion rather than by the cardiovascular system. It is therefore possible to attribute cardiac failure directly to particular genes by ruling out the possibility that it is due to a secondary effect of hypoxia. We focus here on pickwickm171 (pikm171), a recessive lethal mutation discovered in a large-scale genetic screen.