Oncostatin M Receptor Type II Knockout Mitigates Inflammation and Improves Survival from Sepsis in Mice.

Sepsis remains one of the leading causes of death worldwide. Oncostatin M (OSM), an interleukin (IL)-6 family cytokine, can be found at high levels in septic patients. However, little is known about its role in sepsis.

Effect of preoperative long-term opioid therapy on patient outcomes after total knee arthroplasty: an analysis of multicentre population-based administrative data.

Background: Up to 40% of patients are receiving opioids at the time of total knee arthroplasty (TKA) in the United States despite evidence suggesting opioids are ineffective for pain associated with arthritis and have substantial risks. Our primary objective was to determine whether preoperative opioid users had worse knee pain and physical function outcomes 12 months after TKA than patients who were opioid-naive preoperatively; our secondary objective was to determine the prevalence of opioid use before and after TKA in Alberta, Canada.

Methods: In this retrospective analysis of population-based data, we identified adult patients who underwent TKA between 2013 and 2015 in Alberta.

Thigh Ultrasound Used to Identify Frail Elderly Patients with Sarcopenia Undergoing Surgery: A Pilot Study.

Background: Computed tomography (CT) scan quantifying skeletal muscle mass is the gold standard tool to identify sarcopenia. Unfortunately, high cost, limited availability, and radiation exposure limit its use. We suggest that ultrasound of the thigh muscle could be an objective, reproducible, portable, and risk-free tool, used as a surrogate to a CT scan, to help identify frail patients with sarcopenia.

Oncostatin M Plays a Critical Role in Survival after Acute Intestinal Ischemia: Reperfusion Injury.

Acute intestinal ischemia-reperfusion injury (AIIRI) is a devastating clinical condition relevant to multiple diseases processes, including sepsis, trauma, transplantation, and burns. An AIIRI is a contributor to the development of multiple organ dysfunction syndrome (MODS). Oncostatin M (OSM)/oncostatin M receptor (OSMR) signaling is an unrecognized and novel candidate pathway for the mediation of MODS.

Preoperative opioid use is associated with worse patient outcomes after Total joint arthroplasty: a systematic review and meta-analysis.

Background: A significant number of patients use opioids prior to total joint arthroplasty (TJA) in North America and there is growing concern that preoperative opioid use negatively impacts postoperative patient outcomes after surgery. This systematic review and meta-analysis evaluated the current evidence investigating the influence of preoperative opioid use on postoperative patient-reported outcomes (PRO) after total joint arthroplasty.

Methods: A systematic search was performed using Ovid, Embase, Cochrane Library, Scopus, Web of Science Core Collection, CINAHL on February 15th, 2018.

Incidence and predictors of postoperative delirium in the older acute care surgery population: a prospective study.

Background: Among older inpatients, the highest incidence of delirium is within the surgical population. Limited data are available regarding postoperative delirium risk in the acute care surgical population. The purpose of our study was to establish the incidence of and risk factors for delirium in an older acute care surgery population.

Creatine-loading preserves intestinal barrier function during organ preservation.

We have developed a novel, intraluminal preservation solution that is tailored to the metabolic requirements of the intestine. This organ-specific solution addresses many of the problems associated with low temperature organ storage including energy, oxidative and osmotic stresses. However, conservation of energy levels remains one of the most difficult obstacles to overcome due to the inherent sensitivity of the mucosa to ischemia.

Impact of frailty on outcomes after discharge in older surgical patients: a prospective cohort study.

Background: Frailty is a state of vulnerability to diverse stressors. We assessed the impact of frailty on outcomes after discharge in older surgical patients.

Methods: We prospectively followed patients 65 years of age or older who underwent emergency abdominal surgery at either of 2 tertiary care centres and who needed assistance with fewer than 3 activities of daily living.

Analysis of postdischarge costs following emergent general surgery in elderly patients.

Background: As populations age, more elderly patients will undergo surgery. Frailty and complications are considered to increase in-hospital cost in older adults, but little is known on costs following discharge, particularly those borne by the patient. We examined risk factors for increased cost and the type of costs accrued following discharge in elderly surgical patients.

Metabolomic profiling to characterize acute intestinal ischemia/reperfusion injury.

Sepsis and septic shock are the leading causes of death in critically ill patients. Acute intestinal ischemia/reperfusion (AII/R) is an adaptive response to shock. The high mortality rate from AII/R is due to the severity of the disease and, more importantly, the failure of timely diagnosis.

Urine intestinal fatty acid-binding protein predicts acute mesenteric ischemia in patients.

Background: Acute mesenteric ischemia (AMI) has a high morbidity and mortality and often presents as a diagnostic challenge. Currently, there is no blood, urine, or radiologic tests that provide a definitive diagnosis of AMI. The aim of this study was to evaluate the clinical accuracy of urine intestinal fatty acid-binding protein (I-FABP) to diagnosis AMI.

I-FABP as biomarker for the early diagnosis of acute mesenteric ischemia and resultant lung injury.

Acute mesenteric ischemia (AMI) is a life-threatening condition that can result in multiple organ injury and death. A timely diagnosis and treatment would have a significant impact on the morbidity and mortality in high-risk patient population. The purpose of this study was to investigate if intestinal fatty acid binding protein (I-FABP) and α-defensins can be used as biomarkers for early AMI and resultant lung injury.

Human islet mass, morphology, and survival after cryopreservation using the Edmonton protocol.

The aim of this study was to assess recovery, cell death, and cell composition of post-thaw cultured human islets. Cryopreserved islets were provided by the Clinical Islet Transplant Program, Edmonton, Canada. Islets were processed using media prepared in accordance with Pre-Edmonton and Edmonton protocols.

Organ-specific solutions and strategies for the intestinal preservation.

Among the intraabdominal organs, the intestine is the most susceptible to storage injury and as a consequence its safe cold ischemic time in the clinic is restricted to below 10 hours. The current practice for the intestinal preservation (IP) consists of an in-situ vascular flush with iced University of Wisconsin or Histidine-Tryptophan-Ketoglutarate solution followed by cold storage at 4°C. Mucosal injury is initiated within 1 hour and rapidly progresses to mucosal breakdown; tissue injury worsens upon reperfusion and further impairs the mucosal barrier, favoring bacterial translocation and sepsis.

Additive effect of sirolimus and anti-death receptor 5 agonistic antibody against hepatocellular carcinoma.

Background & Aims: Despite careful patient selection, hepatocellular carcinoma (HCC) recurs in 10-20% of cases after liver transplantation, and the use of potent adjuvant anticancer drugs would be welcome. The aim of this study was to evaluate the efficiency of a combined therapy of rapamycin (sirolimus) and anti-death receptor (DR)5 monoclonal antibody (mAb) on HCC.

Methods: We first assessed the side effects of anti-DR5 mAb administration in vivo by giving various doses of anti-DR5 mAb.

Metabolomic profiles are gender, disease and time specific in the interleukin-10 gene-deficient mouse model of inflammatory bowel disease.

Metabolomic profiling can be used to study disease-induced changes in inflammatory bowel diseases (IBD). The aim of this study was to investigate the difference in the metabolomic profile of males and females as they developed IBD. Using the IL-10 gene-deficient mouse model of IBD and wild-type mice, urine at age 4, 6, 8, 12, 16, and 20 weeks was collected and analyzed by nuclear magnetic resonance (NMR) spectroscopy.

Human cytomegalovirus infection in humanized liver chimeric mice.

Aim: Cytomegalovirus is a common viral pathogen that influences the outcome of organ transplantation. To date, there is no established method to evaluate the effects of human CMV (HCMV) treatments in vivo except for human clinical trials. In the current study, we describe the development of a mouse model that supports the in vivo propagation of HCMV.

Small bowel fibrosis and systemic inflammatory response after ileocolonic anastomosis in IL-10 null mice.

Background: Crohn's disease recurrence after an ileocecal resection is common; yet, its pathophysiology is poorly understood and available treatment is suboptimal. The purpose of this study was to examine the bacterial, local, and systemic immune changes that follow ileocolonic anastomosis in a rodent model of Crohn's disease, the interleukin-10 gene-deficient (IL-10 null) mice.

Materials And Methods: We divided wild-type and IL-10 null mice into three treatment groups: ileocolonic anastomosis, sham operation (ileo-ileal anastomosis), and control group without an operation.

Sirolimus drug-eluting, hydrogel-impregnated polypropylene mesh reduces intra-abdominal adhesion formation in a mouse model.

Background: Prosthetic mesh is used frequently in abdominal wall hernia reconstruction but is prone to postoperative adhesion formation. Complications resulting from intra-abdominal adhesions represent a considerable clinical and cost burden. We, herein, investigate the antiproliferative and antiadhesiogenic properties of sirolimus and hydrogel-impregnated, drug-eluting mesh to decrease such complications in a mouse model of abdominal wall hernia repair.

Intravenous injection of endogenous microbial components abrogates DSS-induced colitis.

Background: The etiology of inflammatory bowel diseases (IBD) is largely unknown, but appears to be perpetuated by uncontrolled responses to antigenic components of the endogenous flora. Tolerance to antigenic stimulation can be achieved by exposure to a given antigen in high amounts (high dose tolerance). Colitis induced by feeding of Dextran Sodium Sulfate (DSS) is an often-used animal model mimicking clinical and histological features of human IBD.

Redefining the properties of an osmotic agent in an intestinal-specific preservation solution.

Aim: To investigate the effects of dextrans of various molecular weights (Mw) during a 12 h cold storage time-course on energetics, histology and mucosal infiltration of fluorescein isothiocyanate (FITC)-dextran.

Methods: Rodent intestines were isolated and received a standard University of Wisconsin vascular flush followed by intraluminal administration of a nutrient-rich preservation solution containing dextrans of varying Mw: Group D1, 73 kdal; Group D2, 276 kdal; Group D3, 534 kdal; Group D4, 1185 kdal; Group D5, 2400 kdal.

Results: Using FITC-labeled dextrans, fluorescent micrographs demonstrated varying degrees of mucosal infiltration; lower Mw (groups D1-D3: 73-534 kdal) dextrans penetrated the mucosa as early as 2 h, whereas the largest dextran (D5: 2400 kdal) remained captive within the lumen and exhibited no permeability even after 12 h.

Comparing the effects of Dextran 70 and Hydroxyethyl starch in an intestinal storage solution.

Introduction: Our lab has developed a novel strategy for intestinal preservation involving the intraluminal delivery of a nutrient-rich preservation solution. The aim of this study was to compare the effectiveness of two impermeant agents for use in our solution: Dextran 70 (D70; Mw=70 kDa) and Hydroxyethyl starch (HES; Mw=2200 kDa).

Methods: Rat intestines were procured, including an intravascular flush with University of Wisconsin solution followed by a 'backtable' intraluminal flush with: UW solution (group 1, UW), or an amino acid-based nutrient-rich preservation solution (AA solution) containing either 5% D70 (group 2, AA-D70) or HES (group 3, AA-HES).

Optimizing the concentration of hydroxyethylstarch in a novel intestinal-specific preservation solution.

Introduction: Our lab has developed an effective nutrient-rich solution that facilitates energy production and control of oxidative stress during static cold storage of the intestine; however, the requirement for oncotic agents, such as hydroxyethylstarch (HES), has not been evaluated. This study investigated the effectiveness and requirement for HES in an intraluminal preservation solution during a clinically relevant period of cold storage.

Methods: Rat intestines were procured, including an intravascular flush with University of Wisconsin solution followed by a 'back table' intraluminal flush with a nutrient-rich preservation solution containing varying amounts of HES (n=6 per group): Group 1, 0%; Group 2, 2.

Factors affecting hepatocyte isolation, engraftment, and replication in an in vivo model.

Human hepatocyte transplantation is an alternative treatment for acute liver failure and liver diseases involving enzyme deficiencies. Although it has been successfully applied in selected recipients, both isolation and transplantation outcomes have the potential to be improved by better donor selection. This study assessed the impact of various donor variables on isolation outcomes (yield and viability) and posttransplant engraftment, using the SCID/Alb-uPA (severe combined immunodeficient/urokinase type plasminogen activator under the control of an albumin promoter) human liver chimeric mouse model.

Critical role of natural killer cells in the rejection of human hepatocytes after xenotransplantation into immunodeficient mice.

The severe combined immunodeficiency/albumin linked-urokinase type plasminogen activator (SCID/Alb-uPA) human liver chimeric mouse model has added a new dimension to studies of liver based human diseases and has important potential for study of human hepatic drug metabolism. However, it remains unclear if natural killer (NK) cell in SCID/Alb-uPA mice has an important negative impact on engraftment and expansion of human hepatocytes after transplantation. Here, we explore the role of mouse NK cells in the rejection of transplanted human hepatocytes in SCID/Alb-uPA mice.