Prompt Thrombo-Inflammatory Response to Ischemia-Reperfusion Injury and Kidney Transplant Outcomes.

Introduction: In kidney transplantation (KT), the role of the intravascular innate immune system (IIIS) in response to ischemia-reperfusion injury (IRI) is not well-understood. Here, we studied parallel changes in the generation of key activation products of the proteolytic cascade systems of the IIIS following living donor (LD) and deceased donor (DD) transplantation and evaluated potential associations with clinical outcomes.

Methods: In a cohort study, 63 patients undergoing LD ( = 26) and DD ( = 37) transplantation were prospectively included.

Siplizumab combination therapy with belatacept or abatacept broadly inhibits human T cell alloreactivity in vitro.

Combined antigen-specific T cell receptor stimulation and costimulation are needed for complete T cell activation. Belatacept and abatacept are nondepleting fusion proteins blocking CD28/B7 costimulation, whereas siplizumab is a depleting antiCD2 immunoglobulin G1 monoclonal antibody targeting CD2/CD58 costimulation. Herein, the effect of siplizumab combination therapy with abatacept or belatacept on T cell alloreactivity in mixed lymphocyte reactions was investigated.

Clinical and financial outcomes of per-oral endoscopic myotomy compared to laparoscopic heller myotomy for treatment of achalasia.

Background: Previous studies analyzing short-term outcomes for per-oral endoscopic myotomy (POEM) have shown excellent clinical response rates and shorter operative times compared to laparoscopic Heller myotomy (LHM). Despite this, many payors have been slow to recognize POEM as a valid treatment option. Furthermore, comparative studies analyzing long-term outcomes are limited.

Impact of Urinary Catheterization on Postoperative Outcomes After Roux-En-Y Gastric Bypass Surgery in Propensity-Matched Cohorts.

Background: The impact of urinary catheter avoidance in bariatric enhanced recovery after surgery (ERAS) protocols is yet to be established. The purpose of the current study is to determine whether urinary catheter use in patients undergoing Roux-en-Y gastric bypass (RYGB) procedures has an effect on postoperative outcomes.

Methods: An institutional database was utilized to identify adult patients undergoing primary minimally invasive RYGB surgery.

Siplizumab Induces NK Cell Fratricide Through Antibody-Dependent Cell-Mediated Cytotoxicity.

The glycoprotein CD2 is expressed on T and NK cells and contributes to cell-cell conjugation, agonistic signaling and actin cytoskeleton rearrangement. CD2 has previously been shown to have an important function in natural NK cell cytotoxicity but to be expendable in antibody-mediated cytotoxicity. Siplizumab is a monoclonal anti-CD2 IgG1 antibody that is currently undergoing clinical trials in the field of transplantation.

Polyvinyl Alcohol Carbazate as a Polymer-Based Antitumoral Agent.

Development of treatment resistance is a major concern during treatment of cancer, and there is an unmet need for therapeutic strategies with novel modes of action. Polyvinyl alcohol carbazate (PVAC) is a polymer compound with unique biological properties. Herein, we describe the antitumoral effects of PVAC.

Siplizumab, an Anti-CD2 Monoclonal Antibody, Induces a Unique Set of Immune Modulatory Effects Compared to Alemtuzumab and Rabbit Anti-Thymocyte Globulin .

Antibodies are commonly used in organ transplant induction therapy and to treat autoimmune disorders. The effects of some biologics on the human immune system remain incompletely characterized and a deeper understanding of their mechanisms of action may provide useful insights for their clinical application. The goal of this study was to contrast the mechanistic properties of siplizumab with Alemtuzumab and rabbit Anti-Thymocyte Globulin (rATG).

Long-Term Infectious and Noninfectious Outcomes of Monthly Alemtuzumab as a Calcineurin Inhibitor- and Steroid-Free Regimen for Pancreas Transplant Recipients.

Multiple doses of alemtuzumab for immunosuppressive therapy of patients with hematologic malignancies and hematopoietic stem cell transplant have been associated with a high rate of infection. In transplantation, limited alemtuzumab dosing has been successfully used as induction immunosuppression. The effect of multiple doses of alemtuzumab, used as maintenance therapy to minimize steroid and/or calcineurin inhibitor toxicity in solid organ transplant recipients, is unknown.

Examining emergency department utilization in the post-foregut surgery patient.

Background: The purpose of this study was to examine emergency department (ED) utilization following minimally invasive foregut surgery and determine its impact on costs. Furthermore, we sought to determine their relationship to the index procedure, whether they are preventable, and describe strategies for decreasing unnecessary ED visits.

Methods: A retrospective review was conducted for all patients undergoing foregut procedures from January 2018 through June 2019.

Development and validation of the first consensus gene-expression signature of operational tolerance in kidney transplantation, incorporating adjustment for immunosuppressive drug therapy.

Background: Kidney transplant recipients (KTRs) with "operational tolerance" (OT) maintain a functioning graft without immunosuppressive (IS) drugs, thus avoiding treatment complications. Nevertheless, IS drugs can influence gene-expression signatures aiming to identify OT among treated KTRs.

Methods: We compared five published signatures of OT in peripheral blood samples from 18 tolerant, 183 stable, and 34 chronic rejector KTRs, using gene-expression levels with and without adjustment for IS drugs and regularised logistic regression.

Pharmacogenomics in kidney transplant recipients and potential for integration into practice.

What Is Known And Objective: Pharmacogenomic biomarkers are now used in many clinical care settings and represent one of the successes of precision medicine. Genetic variants are associated with pharmacokinetic and pharmacodynamic changes leading to medication adverse effects and changes in clinical response. Actionable pharmacogenomic variants are common in transplant recipients and have implications for medications used in transplant, but yet are not broadly incorporated into practice.

Clinical Impact of Antecedent Bariatric Surgery on Liver Transplant Outcomes: A Retrospective Matched Case-control Study.

Background: Bariatric surgery (BS) may be associated with significant malabsorption and nutritional deficiencies.

Methods: Between March 1987 and January 2017, we performed 922 liver transplants (LT) at our institution; 33 had antecedent BS. We matched the BS cohort to LT recipients without BS (1:3 matching) based on exact matching for gender and cancer and inverse variance matching for age, LT body mass index, MELD score, and transplant date.

CD2 Immunobiology.

The glycoprotein CD2 is a costimulatory receptor expressed mainly on T and NK cells that binds to LFA3, a cell surface protein expressed on e.g., antigen-presenting cells.

Enteric Conversion of Bladder-drained Pancreas as a Predictor of Outcomes in Almost 600 Recipients at a Single Center.

Unlabelled: Complications associated with bladder-drained pancreata necessitating enteric conversion are common. Data on the outcomes after enteric conversion are conflicting. We studied the association between enteric conversion and the pancreas graft rejection, loss, and mortality.

Phase I trial evaluating safety and efficacy of intratumorally administered inflammatory allogeneic dendritic cells (ilixadencel) in advanced gastrointestinal stromal tumors.

Background: The majority of patients with advanced gastrointestinal stromal tumor (GIST) develop resistance to imatinib, and subsequent treatments have limited efficacy. Ilixadencel (allogeneic inflammatory dendritic cells) is a cell-based immune primer injected intratumorally that previously has been clinically investigated in metastatic renal cell carcinoma and hepatocellular carcinoma.

Methods: The trial was a single arm phase I trial assessing safety and efficacy of ilixadencel in subjects with progressing advanced/metastatic GIST despite ongoing treatment with second or later lines of tyrosine kinase inhibitors (TKI).

Effect of biceps tenodesis on speed of recovery after arthroscopic rotator cuff repair.

Background: Concomitant biceps tendon pathology is often present in patients undergoing rotator cuff repair (RCR). Management of biceps pathology has been reported to influence outcomes of RCR; however, the impact on the pace of recovery remains unclear. The purpose of this study was to analyze the effects of simultaneous RCR with biceps tenodesis (RCR-BT) on time to achieve maximum improvement and recovery speed for pain and function.

Re-hospitalization after pediatric kidney transplant: A single-center study.

Background: Little data exist on re-hospitalization rates in pediatric kidney recipients (KTx) particularly with the evolution of transplant immunosuppression.

Methods: In a single-center, retrospective study of pediatric KTx between 2006 and 2016, we assessed re-hospitalization after KTx admission, stratified by whether the re-admit was early (<30 days post-KTx discharge) or late (>30 days), and compared two different immunosuppression eras (one with and one without steroids).

Results: Of 197 KTx, 156 (79%) patients were re-hospitalized in 1st year, 85 (56%) within 30 days of discharge (total 490 1st year re-hospitalizations).

Management of Three- and Four-Part Proximal Humerus Fractures.

The management of three- and four-part proximal humerus fractures remains controversial because the literature has supported all forms of management, including nonsurgical management, open reduction and internal fixation (ORIF), and shoulder arthroplasty. Specific patient factors ultimately influence the decision of which treatment best fits the patient and the fracture. Surgeons should understand the rationale for nonsurgical and surgical management of these fractures, including ORIF and reverse shoulder arthroplasty.

Polyvinylalcohol-carbazate (PVAC) reduces red blood cell hemolysis.

Background And Objectives: The objective of this study was to investigate whether a soluble polymer and aldehyde-scavenger, polyvinylalcohol-carbazate (PVAC), can inhibit hemolysis in the storage of red blood cells (RBC).

Study Design And Methods: The effect of PVAC was assessed over a wide range of concentrations, using absorption spectroscopy to evaluate the level of hemolysis. Moreover, osmotic stability and aldehyde-scavenging potential of RBC were assessed after storage in PVAC.

Systemic Inflammatory Reaction in Patients With Head and Neck Cancer-An Explorative Study.

To assess the longitudinal pattern of pro-inflammatory cytokines and growth factors in serum up to 1 year following treatment for head and neck cancer. Patients with newly diagnosed, curable head and neck cancer were included ( = 30). The most common subsite was oropharynx ( = 13) followed by oral cavity ( = 9).

Cause of death and significant disease found at autopsy.

The use of clinical autopsy has been in decline for many years throughout healthcare systems of developed countries despite studies showing substantial discrepancies between autopsy results and pre-mortal clinical diagnoses. We conducted a study to evaluate over time the use and results of clinical autopsies in Sweden. We reviewed the autopsy reports and autopsy referrals of 2410 adult (age > 17) deceased patients referred to two University hospitals in Sweden during two plus two years, a decade apart.

Pharmacokinetic and pharmacodynamic study of a clinically effective anti-CD2 monoclonal antibody.

The humanized IgG1κ monoclonal antibody siplizumab and its rat parent monoclonal IgG2b antibody BTI-322 are directed against the CD2 antigen. Siplizumab is species-specific, reacting with human and chimpanzee cells but not with cells from any other species, including other non-human primates. Because siplizumab treatment has recently shown great potential in clinical transplantation, we now present the results of our previous pharmacokinetic, pharmacodynamic and safety studies of both antibodies.