Interventional Approach to Portal Vein Thrombosis and Liver Transplantation: State of the Art.

Porto-mesenteric vein thrombosis (PVT) is a well-recognized but uncommon disease entity in patients with and without cirrhosis. Given the complexity of these patients, there are many differing treatment algorithms depending on the individual circumstances of a given patient. The focus of this review is primarily patients with cirrhosis, with an emphasis on liver transplantation considerations. The presence of cirrhosis substantially affects work-up, prognosis, and management of these patients and will substantially affect the patient treatment and have additional implications for prognosis and long-term outcomes. Here, we review the incidence of portal vein thrombosis in known cirrhotic patients, medical and interventional treatment options that are currently used, and, in particular, how to approach cirrhotic patients with PVT who are awaiting liver transplantation.

New Uses for Thromboelastography and Other Forms of Viscoelastic Monitoring in the Emergency Department: A Narrative Review.

Patients frequently visit the emergency department with conditions that place them at risk of worse outcomes when accompanied by coagulopathy. Routine tests of coagulation-prothrombin time, partial thromboplastin time, platelets, and fibrinogen-have shortcomings that limit their use in providing emergency care. One alternative is to investigate coagulation disturbance with viscoelastic monitoring (VEM), a coagulation test that measures the timing and strength of blood clot development in real time. VEM is widely used and studied in cardiac surgery, liver transplant surgery, anesthesia, and trauma. In this article, we review the technique of VEM and the biologic rationale of using it in addition to routine tests of coagulation in emergency clinical situations. Then, we review the evidence (or lack thereof) for using VEM in the diagnosis and treatment of specific conditions. Finally, we describe the limitations of the test and future directions for clinical use and research in emergency medicine.

Anti-GM-CSF autoantibodies in patients with cryptococcal meningitis.

Cryptococcal meningitis has been described in immunocompromised patients, as well as in those for whom no immune defect has been identified. GM-CSF regulates the function of phagocytes and pulmonary alveolar macrophages, critical elements in cryptococcal control. We performed clinical histories, immunological evaluation, and anticytokine autoantibody screening in four current patients with cryptococcal meningitis and identified and tested 103 archived plasma/cerebrospinal fluid samples from patients with cryptococcal meningitis. We assessed the ability of anti-GM-CSF autoantibody-containing plasmas to inhibit GM-CSF signaling. We recognized anti-GM-CSF autoantibodies in an otherwise healthy female with cryptococcal meningitis who later developed pulmonary alveolar proteinosis (PAP). Her diagnosis prompted screening of patients with cryptococcal meningitis for anticytokine autoantibodies. We identified seven HIV-negative patients with cryptococcal meningitis who tested positive for high-titer anti-GM-CSF autoantibodies. Two of the seven later developed evidence of PAP. Plasma from all patients prevented GM-CSF-induced STAT5 phosphorylation and MIP-1α production in normal PBMCs. This effect was limited to their IgG fraction. Anti-GM-CSF autoantibodies are associated with some cases of cryptococcal meningitis in otherwise immunocompetent patients. These cases need not have associated PAP.

Anti-CD20 (rituximab) therapy for anti-IFN-γ autoantibody-associated nontuberculous mycobacterial infection.

Patients with anti-IFN-γ autoantibodies have impaired IFN-γ signaling, leading to severe disseminated infections with intracellular pathogens, especially nontuberculous mycobacteria. Disease may be severe and progressive, despite aggressive treatment. To address the underlying pathogenic IFN-γ autoantibodies we used the therapeutic monoclonal rituximab (anti-CD20) to target patient B cells. All subjects received between 8 and 12 doses of rituximab within the first year to maintain disease remission. Subsequent doses were given for relapsed infection. We report 4 patients with refractory disease treated with rituximab who had clinical and laboratory evidence of therapeutic response as determined by clearance of infection, resolution of inflammation, reduction of anti-IFN-γ autoantibody levels, and improved IFN-γ signaling.

Parathyroid tumor development involves deregulation of homeobox genes.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome caused by mutations in the MEN1 tumor suppressor gene. Loss of the functional second copy of the MEN1 gene causes individuals to develop multiple endocrine tumors, primarily affecting the parathyroid, pituitary, and pancreas. While it is clear that the protein encoded by MEN1, menin, suppresses endocrine tumors, its biochemical functions and direct downstream targets remain unclear. Recent studies have suggested that menin may act as a scaffold protein to coordinate gene transcription, and that menin is an oncogenic cofactor for homeobox (HOX) gene expression in hematopoietic cancer. The role of HOX genes in adult cell differentiation is still obscure, but growing evidence suggests that they may play important roles in the development of cancer. Therefore, we hypothesized that specific HOX genes were regulated by menin in parathyroid tumor development. Utilizing quantitative TaqMan RT-PCR, we compared expression profiles of the 39 HOX genes in human familial MEN1 (fMEN1) parathyroid tumors and sporadic parathyroid adenomas with normal samples. We identified a large set of 23 HOX genes whose deregulation is specific for fMEN1 parathyroid tumors, and only 5 HOX genes whose misexpression are specific for sporadic parathyroid tumor development. These findings provide the first evidence that loss of the MEN1 tumor suppressor gene is associated with deregulation of specific HOX gene expression in the development of familial human parathyroid tumors. Our results strongly reinforce the idea that abnormal expression of developmental HOX genes can be critical in human cancer progression.