Publications by authors named "Dirk J Van der Windt"

Background: Acute incisional hernia incarceration is associated with high morbidity and mortality yet there is little evidence to guide which patients will benefit most from prophylactic repair. We explored baseline computed tomography (CT) characteristics associated with incarceration.

Methods: A case-control study design was utilized to explore adults (≥18 years) diagnosed with an incisional hernia between 2010 and 2017 at a single institution with a 1-year minimum follow-up.

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Background: We sought to explore the impact of sex, race, and insurance status on operative management of incisional hernias.

Methods: A retrospective cohort study was conducted to explore adult patients diagnosed with an incisional hernia. Adjusted odds for non-operative versus operative management and time to repair were queried.

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Aim: The use of kidneys donated after circulatory death (DCD) provides an invaluable expansion of the organ supply for transplantation. Here, we investigated the effect of DCD on fibrotic changes on 1 1-year post 1-transplant surveillance kidney allograft biopsy.

Methods: Recipients of a deceased donor kidney transplant between 2013 and 2017 at a single institution, who survived 1 year and underwent surveillance biopsy, were included in the analysis (n = 333: 87 DCD kidneys, 246 kidneys donated after brain death [DBD]).

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Rabbit antithymocyte globulin is a lymphocytedepleting agent commonly used as induction therapy in kidney transplants. Although its use is generally safe and well tolerated, serious side effects can occur. Here, we describe a case of a severe immune complex hypersensitivity reaction with disseminated intravascular coagulation in response to rabbit antithymocyte globulin infusion.

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Background: Regulatory T cell (Treg) therapy is a promising approach to amelioration of allograft rejection and promotion of organ transplant tolerance. However, the fate of infused Treg, and how this relates to their therapeutic efficacy using different immunosuppressive regimens is poorly understood. Our aim was to analyze the tissue distribution, persistence, replicative activity and phenotypic stability of autologous, donor antigen alloreactive Treg (darTreg) in anti-thymocyte globulin (ATG)-lymphodepleted, heart-allografted cynomolgus monkeys.

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Background: Incisional hernia develops in up to 20% of patients undergoing abdominal operations. We sought to identify characteristics associated with poor outcomes after acute incisional hernia incarceration.

Study Design: We performed a retrospective cohort study of adult patients with incisional hernias undergoing elective repair or with acute incarceration between 2010 and 2017.

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Objective: The aim of the study was to quantify the risk of incarceration of incisional hernias.

Background: Operative repair is the definitive treatment for incisional ventral hernias but is often deferred if the perceived risk of elective operation is elevated secondary to comorbid conditions. The risk of incarceration during nonoperative management (NOM) factors into shared decision making by patient and surgeon; however, the incidence of acute incarceration remains largely unknown.

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Innate immunity can initiate platelet activation during the development of thrombosis through a process, termed immunothrombosis. Neutrophils form neutrophil extracellular traps (NETs) that have been shown to interact directly with platelets and play pro-coagulant roles in a variety of infectious and sterile inflammatory settings. Hepatic surgical stress initiated by ischemia/reperfusion (I/R) injury has wide systemic consequences on distant organs.

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The article describes and illustrates the surgical techniques and the post-operative imaging anatomy in liver transplantation. Special attention is paid to the variant vascular and biliary anatomy that are important for surgical planning. Considering the ever-growing number of liver transplants performed and the key role that imaging plays in the pre-operative planning and post-operative assessment, it is important for the radiologist to be familiar with the surgical techniques and the normal post-operative appearance in these patients.

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Transplantation of kidneys from deceased donors with acute kidney injury (AKI) can expand the donor pool. We investigated the effect of donor AKI on renal function and chronic changes on protocol biopsies at 1-year post-transplant. Donor AKI was defined according to Acute Kidney Injury Network (AKIN) criteria.

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Neutrophil infiltration and neutrophil extracellular traps (NET) in solid cancers are associated with poorer prognosis, but the mechanisms are incompletely understood. We hypothesized that NETs enhance mitochondrial function in tumor cells, providing extra energy for accelerated growth. Metastatic colorectal cancer tissue showed increased intratumoral NETs and supranormal preoperative serum MPO-DNA, a NET marker.

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Background: The Risk Analysis Index (RAI) for frailty is a rapid survey for comorbidities and performance status, which predicts mortality after general surgery. We aimed to validate the RAI in predicting outcomes after hepatopancreatobiliary surgery.

Methods: Associations of RAI, determined in 162 patients prior to undergoing hepatopancreatobiliary surgery, with prospectively collected 30-day post-operative outcomes were analyzed with multivariate logistic and linear regression.

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Unlabelled: Nonalcoholic steatohepatitis (NASH) is a progressive, inflammatory form of fatty liver disease. It is the most rapidly rising risk factor for the development of hepatocellular carcinoma (HCC), which can arise in NASH with or without cirrhosis. The inflammatory signals promoting the progression of NASH to HCC remain largely unknown.

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The increasing prevalence of obesity has made nonalcoholic fatty liver disease (NAFLD) the most common chronic liver disease. As a consequence, NAFLD and especially its inflammatory form nonalcoholic steatohepatitis (NASH) are the fastest increasing etiology of end-stage liver disease and hepatocellular carcinoma. Physical inactivity is related to the severity of fatty liver disease irrespective of body weight, supporting the hypothesis that increasing physical activity through exercise can improve fatty liver disease.

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Background & Aims: Neutrophils and liver sinusoidal endothelial cells (LSECs) both contribute to sterile inflammatory injury during ischemia/reperfusion (I/R), a well-known liver surgical stress. Interleukin-33 (IL-33) has been shown to drive neutrophil infiltration during inflammatory responses through its receptor ST2. We recently reported that infiltrating neutrophils form neutrophil extracellular traps (NETs), which exacerbate sterile inflammatory injury in liver I/R.

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Unlabelled: The ability of cancer cells to survive and grow under hypoxic conditions has been known for decades, but the mechanisms remain poorly understood. Under certain conditions, cancer cells undergo changes in their bioenergetic profile to favor mitochondrial respiration by activating the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) and up-regulating mitochondrial biogenesis. In this study, we hypothesized that augmented mitochondrial biogenesis plays a critical role for cancer cells to survive hypoxia.

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Background: The pig-to-non-human primate model is the standard choice for in vivo studies of organ and cell xenotransplantation. In 1998, Lambrigts and his colleagues surveyed the entire world literature and reported all experimental studies in this model. With the increasing number of genetically engineered pigs that have become available during the past few years, this model is being utilized ever more frequently.

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Background: Large animals treated with immunosuppressive drugs for preclinical experiments of transplantation have increased risks of infection, which can be compounded by the induction of diabetes if islet transplantation is planned.

Methods: We report our experience with severe sepsis in two young cynomolgus monkeys and five pigs that were subjected to diabetes induction, immunosuppressive therapy, or islet allotransplantation.

Results: In two monkeys and five pigs, infection was associated with a syndrome of profound hypoglycemia accompanied by severe acidosis, which was resistant to treatment.

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Currently, islet transplantation as a cell therapeutic option for type 1 diabetes occurs via islet injection into the portal vein. Direct contact between islets and blood is a pathophysiological "provocation" that results in the instant blood-mediated inflammatory reaction (IBMIR) and is associated with early islet loss. However, the nature of the various insults on the islets in the blood stream remains mostly unknown.

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Background: We set out to determine whether B-cell tolerance to A/B-incompatible alloantigens and pig xenoantigens could be achieved in infant baboons.

Methods: Artery patch grafts were implanted in the abdominal aorta in 3-month-old baboons using A/B-incompatible (AB-I) allografts or wild-type pig xenografts (pig). Group 1 (Gp1) (controls, n=6) received no immunosuppressive therapy (IS) and no graft.

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Laboratory mice are born lymphopenic and demonstrate lymphopenia-induced proliferation that generates memory T cells, yet they are prone to immunologic tolerance. Here we tested whether these fundamental immunologic observations apply to higher animals by studying the immune system of infant baboons. Using flow cytometry of the peripheral blood cells, it was found that baboons are born relatively lymphopenic and subsequently expand their initially naïve T cell pool with increasing numbers of memory T cells.

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The shortage of organs and cells from deceased individuals continues to restrict allotransplantation. Pigs could provide an alternative source of tissue and cells but the immunological challenges and other barriers associated with xenotransplantation need to be overcome. Transplantation of organs from genetically modified pigs into non-human primates is now not substantially limited by hyperacute, acute antibody-mediated, or cellular rejection, but other issues have become more prominent, such as development of thrombotic microangiopathy in the graft or systemic consumptive coagulopathy in the recipient.

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