Temporal dynamics of persistent germinal centers and memory B cell differentiation following respiratory virus infection.

Following infection or immunization, memory B cells (MBCs) and long-lived plasma cells provide humoral immunity that can last for decades. Most principles of MBC biology have been determined with hapten-protein carrier models or fluorescent protein immunizations. Here, we examine the temporal dynamics of the germinal center (GC) B cell and MBC response following mouse influenza A virus infection.

Assembly of a spatial circuit of T-bet-expressing T and B lymphocytes is required for antiviral humoral immunity.

Effective antiviral immunity requires generation of T and B lymphocytes expressing the transcription factor T-bet, a regulator of type 1 inflammatory responses. Using T-bet expression as an endogenous marker for cells participating in a type 1 response, we report coordinated interactions of T-bet-expressing T and B lymphocytes on the basis of their dynamic colocalization at the T cell zone and B follicle boundary (T-B boundary) and germinal centers (GCs) during lung influenza infection. We demonstrate that the assembly of this circuit takes place in distinct anatomical niches within the draining lymph node, guided by CXCR3 that enables positioning of T1 cells at the T-B boundary.

Outcomes of hepatitis C virus seropositive donors to hepatitis C virus seronegative liver recipients: A large single center analysis.

Introduction And Objectives: The success of direct-acting antivirals (DAA) has transformed the management of hepatitis C virus (HCV) infection and has led to the expansion of the deceased donor organ pool for liver transplantation.

Material And Methods: We present a single center retrospective review of liver transplantations performed on HCV-seronegative recipients from HCV-seropositive organs from 11/2017 to 05/2020. HCV nucleic acid testing (NAT) was performed on HCV-seropositive donors to assess active HCV infection.

Nuclear receptor LXRβ controls fitness and functionality of activated T cells.

T cells increase cholesterol biosynthesis upon activation to generate substrates for cellular growth and proliferation. The ubiquitously expressed liver X receptor β (LXRβ) encoded by the Nr1h2 gene is a critical regulator of cholesterol homeostasis in mammalian cells; however, its cell-intrinsic role in T cell biology remains poorly understood. We report that ablation of LXRβ in T cells leads to spontaneous T cell activation and T lymphocytopenia.

Thirty-day readmission rates, trends and its impact on liver transplantation recipients: a national analysis.

Reduction of early hospital readmissions is a declared goal in the United States economic and quality improvement agenda. A retrospective study was performed using the Nationwide Readmissions Database from 2010 to 2014. Our primary aim was to study the rate of early readmissions and its predictors in liver transplant recipients (LTRs).

Cannabis use may reduce healthcare utilization and improve hospital outcomes in patients with cirrhosis.

Introduction And Objectives: Previous studies reveal conflicting data on the effect of cannabis use in patients with cirrhosis. This research evaluates the impact of cannabis on hepatic decompensation, health care utilization, and mortality in patients with cirrhosis.

Material And Methods: A retrospective analysis of the State Inpatient Database (SID) was performed evaluating patients from Colorado and Washington in 2011 to represent pre-cannabis legalization and 2015 to represent post-cannabis legalization.

Anti-CD40 antibody 2C10 binds to a conformational epitope at the CD40-CD154 interface that is conserved among primate species.

The antagonistic anti-CD40 antibody, 2C10, and its recombinant primate derivative, 2C10R4, are potent immunosuppressive antibodies whose utility in allo- and xenotransplantation have been demonstrated in nonhuman primate studies. In this study, we defined the 2C10 binding epitope and found only slight differences in affinity of 2C10 for CD40 derived from four primate species. Staining of truncation mutants mapped the 2C10 binding epitope to the N-terminal portion of CD40.

A validated risk model for prediction of early readmission in patients with hepatic encephalopathy.

Introduction And Aim: Hepatic encephalopathy (HE) is a common complication in cirrhotics and is associated with an increased healthcare burden. Our aim was to study independent predictors of 30-day readmission and develop a readmission risk model in patients with HE. Secondary aims included studying readmission rates, cost, and the impact of readmission on mortality.

Validation of Risk Score in Predicting Early Readmissions in Decompensated Cirrhotic Patients: A Model Based on the Administrative Database.

Early readmission in patients with decompensated liver cirrhosis leads to an enormous burden on health care use. A retrospective cohort study using the 2013 and 2014 Nationwide Readmission Database (NRD) was conducted. Patients with a diagnoses of cirrhosis and at least one feature of decompensation were included.

Paracentesis in cirrhotics is associated with increased risk of 30-day readmission.

Aim: To determine the readmission rate, its reasons, predictors, and cost of 30-d readmission in patients with cirrhosis and ascites.

Methods: A retrospective analysis of the nationwide readmission database (NRD) was performed during the calendar year 2013. All adults cirrhotics with a diagnosis of ascites, spontaneous bacterial peritonitis, or hepatic encephalopathy were identified by ICD-9 codes.

Effect of transplant center volume on post-transplant survival in patients listed for simultaneous liver and kidney transplantation.

Aim: To examine the effect of center size on survival differences between simultaneous liver kidney transplantation (SLKT) and liver transplantation alone (LTA) in SLKT-listed patients.

Methods: The United Network of Organ Sharing database was queried for patients ≥ 18 years of age listed for SLKT between February 2002 and December 2015. Post-transplant survival was evaluated using stratified Cox regression with interaction between transplant type (LTA SLKT) and center volume.

Rotational Thromboelastometry or Conventional Coagulation Tests in Liver Transplantation: Comparing Blood Loss, Transfusions, and Cost.

Introduction: Orthotopic liver transplantation (OLT) can be associated with significant bleeding requiring multiple blood product transfusions. Rotational thromboelastometry (ROTEM) is a point-of-care device that has been used to monitor coagulation during OLT. Whether it reduces blood loss/transfusions during OLT remains controversial.

Depletion of Gut-Resident CCR5 Cells for HIV Cure Strategies.

The HIV reservoir forming at the earliest stages of infection is likely composed of CCR5 cells, because these cells are the targets of transmissible virus. Restriction of the CCR5 reservoir, particularly in the gut, may be needed for subsequent cure attempts. Strategies for killing or depleting CCR5 cells have been described, but none have been tested in vivo in nonhuman primates, and the extent of achievable depletion from tissues is not known.

Isolation of a monoclonal antibody from a phage display library binding the rhesus macaque MHC class I allomorph Mamu-A1*001.

Monoclonal antibodies that bind to human leukocyte antigen (HLA) are useful tools for HLA-typing, tracking donor-recipient chimerisms after bone marrow transplants, and characterizing specific major histocompatibility complexes (MHC) on cell surfaces. Unfortunately, equivalent reagents are not available for rhesus macaques, which are commonly used animal as models in organ transplant and infectious disease research. To address this deficiency, we isolated an antibody that recognizes the common Indian rhesus macaque MHC class I molecule, Mamu-A1*001.

Impact of transjugular intrahepatic porto-systemic shunt on post liver transplantation outcomes: Study based on the United Network for Organ Sharing database.

Aim: To determine the impact of transjugular intrahepatic porto-systemic shunt (TIPS) on post liver transplantation (LT) outcomes.

Methods: Utilizing the United Network for Organ Sharing (UNOS) database, we compared patients who underwent LT from 2002 to 2013 who had underwent TIPS to those without TIPS for the management of ascites while on the LT waitlist. The impact of TIPS on 30-d mortality, length of stay (LOS), and need for re-LT were studied.

Impact of Recipient and Donor Obesity Match on the Outcomes of Liver Transplantation: All Matches Are Not Perfect.

There is a paucity of literature examining recipient-donor obesity matching on liver transplantation outcomes. The United Network for Organ Sharing database was queried for first-time recipients of liver transplant whose age was ≥18 between January 2003 and September 2013. Outcomes including patient and graft survival at 30 days, 1 year, and 5 years and overall, liver retransplantation, and length of stay were compared between nonobese recipients receiving a graft from nonobese donors and obese recipient-obese donor, obese recipient-nonobese donor, and nonobese recipient-obese donor pairs.

Pretransplant Locoregional Therapy for Hepatocellular Carcinoma: Evaluation of Explant Pathology and Overall Survival.

Background And Objectives: Liver transplant is an important treatment option for patients with hepatocellular carcinoma (HCC) within Milan criteria. We sought to determine the rate of complete tumor necrosis after bridging therapy.

Methods: The medical records of all 178 patients undergoing liver transplantation between January 1, 2008 and July 31, 2015 were reviewed.

Systemic administration of an HIV-1 broadly neutralizing dimeric IgA yields mucosal secretory IgA and virus neutralization.

We investigated the mucosal distribution and neutralization potency of rhesus recombinant versions of the HIV-specific, broadly neutralizing antibody b12 (RhB12) following intravenous administration to lactating rhesus monkeys. IgG and dimeric IgA (dIgA) administration resulted in high plasma concentrations of broadly neutralizing antibody (bnAb), but the monomeric IgA (mIgA) was rapidly cleared from the systemic compartment. Interestingly, differences in the distribution of the RhB12 isoform were observed between the mucosal compartments.

Radiofrequency Wire Recanalization of Chronically Thrombosed TIPS.

Radiofrequency (RF) guide wires have been applied to cardiac interventions, recanalization of central venous thromboses, and to cross biliary occlusions. Herein, the use of a RF wire technique to revise chronically occluded transjugular intrahepatic portosystemic shunts (TIPS) is described. In both cases, conventional TIPS revision techniques failed to revise the chronically thrombosed TIPS.

An indeterminate nodule in the cirrhotic liver discovered by surveillance imaging is a prelude to malignancy.

Background: Surveillance imaging often shows indeterminate lesions in the cirrhotic liver, which may represent early hepatocellular carcinoma (HCC), dysplastic or regenerative nodules, or vascular shunts. The risk of HCC after identification of an indeterminate nodule is not well described.

Methods: We identified 252 patients with cirrhosis and at least one indeterminate nodule discovered on surveillance imaging over a 4-year period.

Hepatic preservation injury: severity of hepatitis C recurrence and survival after liver transplantation.

Background: Preservation injury in the HCV liver transplant population has been reported to correlate with poorer survival outcomes compared to preservation injury in the non-HCV liver transplant population. However, determinants of progression to cirrhosis in HCV infection remain poorly defined in this population.

Aim: This study aimed to determine if the presence and severity of preservation injury impact the acceleration of HCV recurrence and survival after liver transplant.

Inflammatory markers are associated with outcome in patients with unresectable hepatocellular carcinoma undergoing transarterial chemoembolization.

Background: The serum neutrophil-lymphocyte ratio (NLR) is associated with outcomes in several solid organ cancers, including hepatocellular carcinoma (HCC).

Methods: We reviewed our experience in patients with HCC who underwent transarterial chemoembolization (TACE) as the initial treatment. Serum complete blood counts were used to calculate the NLR before and after TACE.

New therapies in the management of hepatitis C virus.

Purpose Of Review: The present review discusses recent developments in drug discovery for hepatitis C. We are on the verge of a new era with the introduction of direct acting oral agents that will transform the treatment landscape. Both healthcare providers and patients need to stay abreast of these changes that will influence decisions to treat.

Endoscopic ultrasonography guided celiac plexus neurolysis and celiac plexus block in the management of pain due to pancreatic cancer and chronic pancreatitis.

Pain is a common symptom of pancreatic disease and is frequently difficult to manage. Pain relief provided by narcotics is often suboptimal and is associated with significant side effects. An alternative approach to pain management in pancreatic disease is the use of celiac plexus block (CPB) or neurolysis (CPN).