Randomized trial investigating the utility of a liver tissue transcriptional biomarker in identifying adult liver transplant recipients not requiring maintenance immunosuppression.

The maintenance of stable allograft status in the absence of immunosuppression, known as operational tolerance, can be achieved in a small proportion of liver transplant recipients, but we lack reliable tools to predict its spontaneous development. We conducted a prospective, multi-center, biomarker-strategy design, immunosuppression withdrawal clinical trial to determine the utility of a predictive biomarker of operational tolerance. The biomarker test, originally identified in a patient cohort with high operational tolerance prevalence, consisted of a 5-gene transcriptional signature measured in liver tissue collected before initiating immunosuppression weaning.

Donor-specific immune senescence as a candidate biomarker of operational tolerance following liver transplantation in adults: Results of a prospective, multicenter cohort study.

Immunosuppression can be withdrawn from selected liver transplant recipients, although robust clinical predictors of tolerance remain elusive. The Immune Tolerance Network ITN056ST study (OPTIMAL; NCT02533180) assessed clinical outcomes and mechanistic correlates of phased immunosuppression withdrawal (ISW) in nonautoimmune, nonviral adult liver transplant recipients. Enrolled subjects were ≥3 years posttransplant with minimal/absent inflammation or fibrosis on a screening liver biopsy.

Hypothermic oxygenated machine perfusion influences the immunogenicity of donor livers in humans.

Hypothermic oxygenated machine perfusion (HOPE) is an organ preservation strategy shown to reduce ischemia-reperfusion injury (IRI)-related complications following liver transplantation. In animal models, HOPE can also decrease alloimmune responses after transplantation, but this remains to be evaluated in humans. Our study, involving 27 patients undergoing liver transplantation enrolled in 2 randomized controlled trials comparing static cold storage with HOPE (14 HOPE-treated and 13 static cold storage-treated), delves into the impact of HOPE on the molecular profile of liver allografts and on the immune responses elicited after transplantation.

International Benchmark for Total Metabolic Tumor Volume Measurement in Baseline F-FDG PET/CT of Lymphoma Patients: A Milestone Toward Clinical Implementation.

Total metabolic tumor volume (TMTV) is prognostic in lymphoma. However, cutoff values for risk stratification vary markedly, according to the tumor delineation method used. We aimed to create a standardized TMTV benchmark dataset allowing TMTV to be tested and applied as a reproducible biomarker.

Cellular uptake and in vivo distribution of mesenchymal-stem-cell-derived extracellular vesicles are protein corona dependent.

Extracellular vesicles (EVs) derived from mesenchymal stem cells are promising nanotherapeutics in liver diseases due to their regenerative and immunomodulatory properties. Nevertheless, a concern has been raised regarding the rapid clearance of exogenous EVs by phagocytic cells. Here we explore the impact of protein corona on EVs derived from two culturing conditions in which specific proteins acquired from media were simultaneously adsorbed on the EV surface.

Time since liver transplant and immunosuppression withdrawal outcomes: Systematic review and individual patient data meta-analysis.

Background & Aims: Successful immunosuppression withdrawal (ISW) is possible for a subfraction of liver transplant (LT) recipients but the factors that define the risk of ISW failure are largely unknown. One candidate prognostic factor for ISW success or operational tolerance (OT) is longer time between LT and ISW which we term "pre-withdrawal time". To clarify the impact of pre-withdrawal time span on subsequent ISW success or failure, we conducted a systematic review with meta-analysis.

HCV spontaneous clearers showed low senescence profile in people living with HIV under long ART.

Coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) increases immune activation, inflammation, and oxidative stress that could lead to premature senescence. Different HCV infections, either acute or chronic infection, could lead to distinct premature cellular senescence in people living with HIV (PLWHIV). Observational study in 116 PLWHIV under antiretroviral treatment with different HCV status: (i) n = 45 chronically infected with HCV (CHC); (ii) n = 36 individuals who spontaneously clarify HCV (SC); (iii) n = 35 HIV controls.

Liver transplantation immunology: Immunosuppression, rejection, and immunomodulation.

Outcomes after liver transplantation have continuously improved over the past decades, but long-term survival rates are still lower than in the general population. The liver has distinct immunological functions linked to its unique anatomical configuration and to its harbouring of a large number of cells with fundamental immunological roles. The transplanted liver can modulate the immunological system of the recipient to promote tolerance, thus offering the potential for less aggressive immunosuppression.

A Bedside Equation to Estimate Endotracheal Tube Length for Infants.

Objective: To develop a bedside equation that can be used to estimate the ideal oral and nasal endotracheal tube (ETT) length for children younger than 1 year of age.

Study Design: Retrospective database analysis of 735 children younger than 1 year of age admitted to pediatric intensive care at Evelina London Children's Hospital from June 1, 2019, through August 31, 2021. ETT positions were determined by tube-tip superimposition over vertebral body on postintubation chest radiograph by trained medical students and pediatric radiologists with bedside assessment of ETT length at nostril or lip as recorded electronically by nursing staff.

Can regulatory T cells improve outcomes of sensitised patients after HLA-Ab incompatible renal transplantation: study protocol for the Phase IIa GAMECHANgER-1 trial.

Background: Kidney transplantation is the gold-standard treatment for patients with kidney failure. However, one-third of patients awaiting a kidney transplant are highly sensitized to human leukocyte antigens (HLA), resulting in an increased waiting time for a suitable kidney, more acute and chronic rejection, and a shorter graft survival compared to non-highly sensitised patients. Current standard immunosuppression protocols do not adequately suppress memory responses, and so alternative strategies are needed.

Dynamics of cellular senescence markers after HCV elimination spontaneously or by DAAs in people living with HIV.

Background: We identified that acute or chronic Hepatitis C (HCV) infection in people living with HIV (PLWHIV) results in different senescence profiles. However, variations in these profiles after HCV elimination, spontaneously or with direct-acting antivirals (DAAs), remain unclear.

Methods: Longitudinal observational study (48 weeks) in 70 PLWHIV: 23 PLWHIV with active HCV-chronic infection (CHC) before and after HCV eradication with DAAs, 12 PLWHIV who spontaneously clarify the HCV (SC), and 35 controls (HIV).

Baseline PET radiomics outperforms the IPI risk score for prediction of outcome in diffuse large B-cell lymphoma.

The objective of this study is to externally validate the clinical positron emission tomography (PET) model developed in the HOVON-84 trial and to compare the model performance of our clinical PET model using the international prognostic index (IPI). In total, 1195 patients with diffuse large B-cell lymphoma (DLBCL) were included in the study. Data of 887 patients from 6 studies were used as external validation data sets.

Containment and conversion: Urban livelihoods and the circulation of value amid South Africa's avian influenza outbreak.

In South Africa the racialized contours of economic life powerfully shape the distribution of who owns poultry enterprises, who is employed to labor in them, who consumes poultry products, and in which way. When, in late 2017, an outbreak of highly pathogenic avian influenza (H5N8) decimated the South African poultry sector, it revealed the ontological transformations of industrial egg-laying poultry into "cull birds" and then into , the quintessential rural chicken. It thus showed how distinct regimes of value "articulate," blurring infectious and noninfectious concerns as new chains of conversion were inaugurated across domestic and global economies.

Selective decrease of donor-reactive T after liver transplantation limits T therapy for promoting allograft tolerance in humans.

Promoting immune tolerance to transplanted organs can minimize the amount of immunosuppressive drugs that patients need to take, reducing lifetime risks of mortality and morbidity. Regulatory T cells (T) are essential for immune tolerance, and preclinical studies have shown their therapeutic efficacy in inducing transplantation tolerance. Here, we report the results of a phase 1/2 trial (ARTEMIS, NCT02474199) of autologous donor alloantigen-reactive T (darT) therapy in individuals 2 to 6 years after receiving a living donor liver transplant.

Feasibility and acceptability of an education and training e-resource to support the sexuality, intimacy and relationship needs of older care home residents: a mixed methods study.

Background: sexuality, intimacy and relationship needs are often a neglected aspect of the care of older adults in residential care facilities. Improving awareness, knowledge and improving attitudes about these needs among care staff could enhance quality of care and lead to better outcomes for residents.

Objective: to evaluate the feasibility and acceptability of a co-designed education and training e-resource to help care staff support their residents' sexuality, intimacy and relationship needs.

The Feasibility and User-Experience of a Digital Health Intervention Designed to Prevent Weight Gain in New Kidney Transplant Recipients-The ExeRTiOn2 Trial.

Unlabelled: Half of kidney transplant recipients (KTRs) gain more than 5% of their body weight in the first year following transplantation. KTRs have requested support with physical activity (PA) and weight gain prevention, but there is no routine care offered. There are few high-quality studies investigating the clinical value of diet, PA or combined interventions to prevent weight gain.

Proposed New Dynamic Prognostic Index for Diffuse Large B-Cell Lymphoma: International Metabolic Prognostic Index.

Purpose: Baseline metabolic tumor volume (MTV) is a promising biomarker in diffuse large B-cell lymphoma (DLBCL). Our aims were to determine the best statistical relationship between MTV and survival and to compare MTV with the International Prognostic Index (IPI) and its individual components to derive the best prognostic model.

Methods: PET scans and clinical data were included from five published studies in newly diagnosed diffuse large B-cell lymphoma.

Cost-Effectiveness of Shortening Treatment Duration Based on Interim PET Outcome in Patients With Diffuse Large B-cell Lymphoma.

Background: Guideline recommendations for diffuse large-B-cell lymphoma (DLBCL) treatment are shifting from long to short treatment duration, although it is still unclear whether shortening treatment duration does not cause any harm. As interim PET (I-PET) has high negative predictive value for progression, we evaluated the cost-effectiveness of shortening treatment duration dependent on I-PET result.

Materials And Methods: We developed a Markov cohort model using the PET Re-Analysis (PETRA) database to evaluate a long treatment duration (LTD) strategy, ie 8x R-CHOP or 6x R-CHOP plus 2 R, and a short treatment duration (STD) strategy, ie 6x R-CHOP.

Use of rapid cardiac magnetic resonance imaging to guide chelation therapy in patients with transfusion-dependent thalassaemia in India: UMIMI study.

Aims: To explore the impact of incorporating a faster cardiac magnetic resonance (CMR) imaging protocol in a low-middle-income country (LMIC) and using the result to guide chelation in transfusion-dependent patients.

Methods And Results: A prospective UK-India collaborative cohort study was conducted in two cities in India. Two visits 13 months apart included clinical assessment and chelation therapy recommendations based on rapid CMR results.

Non-invasive alloimmune risk stratification of long-term liver transplant recipients.

Background & Aims: Management of long-term immunosuppression following liver transplantation (LT) remains empirical. Surveillance liver biopsies in combination with transcriptional profiling could overcome this challenge by identifying recipients with active alloimmune-mediated liver damage despite normal liver tests, but this approach lacks applicability. Our aim was to investigate the utility of non-invasive tools for the stratification of stable long-term survivors of LT, according to their immunological risk and need for immunosuppression.

Is the Gothic Arch a reliable radiographic landmark for migration percentage in children with cerebral palsy?

Introduction: Reimers migration percentage (MP) is the gold standard for measuring hip displacement in children with cerebral palsy (CP). Hip surveillance registries proposed using the top of the Gothic arch (GA) as a modification in patients with acetabular dysplasia because the classical method (CM) described by Reimers may underestimate hip migration. The aim of this study is to assess the inter- and intra-observer reliability of the modified method (MM) versus the CM and identify their effect on the MP.

Understanding, predicting and achieving liver transplant tolerance: from bench to bedside.

In the past 40 years, liver transplantation has evolved from a high-risk procedure to one that offers high success rates for reversal of liver dysfunction and excellent patient and graft survival. The liver is the most tolerogenic of transplanted organs; indeed, immunosuppressive therapy can be completely withdrawn without rejection of the graft in carefully selected, stable long-term liver recipients. However, in other recipients, chronic allograft injury, late graft failure and the adverse effects of anti-rejection therapy remain important obstacles to improved success.