IL-1 Signal Inhibition in Alcohol-Related Hepatitis: A Randomized, Double-Blind, Placebo-Controlled Trial of Canakinumab.

Background And Aims: Short-term mortality in alcohol-related hepatitis (AH) is high, and no current therapy results in durable benefit. A role for interleukin (IL)-1β has been demonstrated in the pathogenesis of alcohol-induced steatohepatitis. This study explored the safety and efficacy of canakinumab (CAN), a monoclonal antibody targeting IL-1β, in the treatment of patients with AH.

SARS-CoV-2 variant evolution in the United States: High accumulation of viral mutations over time likely through serial Founder Events and mutational bursts.

Since the first case of COVID-19 in December 2019 in Wuhan, China, SARS-CoV-2 has spread worldwide and within a year and a half has caused 3.56 million deaths globally. With dramatically increasing infection numbers, and the arrival of new variants with increased infectivity, tracking the evolution of its genome is crucial for effectively controlling the pandemic and informing vaccine platform development.

How well has part-time work on return from maternity leave been accepted in the workplace? Learnings from allied health professional managers in Queensland Health.

Objective The aim of this study was to explore allied health professional (AHP) managers' implementation of the right to request part-time hours on return from maternity leave in Queensland Health (QH) hospitals. Methods Qualitative data were collected via interviews with AHP managers from a cross-section of professions with variations in workforce size and gender composition. Interviews were audio recorded, transcribed and analysed thematically.

A Very Short Course of HBIg+NA Followed by Entecavir or Tenofovir Monotherapy Prevents HBV Recurrence in Low-Risk Liver Transplant Recipients.

Background: Monoprophylaxis with third-generation nucleos(t)ide analogues (NAs) can be safely adopted in hepatitis B virus (HBV)-positive, liver transplantation (LT) patients after at least 6 months of HBV immunoglobulin (HBIg)+NA. We investigated the efficacy of earlier initiation of post-LT entecavir (ETV) or tenofovir (TDF) monoprophylaxis.

Methods: Between September 2011 and January 2017, all consecutive hepatitis B surface antigen (HBsAg)-positive transplanted patients were scheduled to receive HBIg with ETV or TDF for a period related to the risk for HBV reinfection: 1.

On the impact of hepatitis C virus and heterologous immunity on alloimmune responses following liver transplantation.

Virus-induced heterologous immunity is considered a barrier to transplantation tolerance. Yet, hepatitis C (HCV)-infected liver transplant (LT) patients occasionally achieve operational tolerance. We investigated the mechanisms through which HCV infection modulates donor-specific T cell responses following LT and the influence of HCV eradication.

Applicability, safety, and biological activity of regulatory T cell therapy in liver transplantation.

Regulatory T cells (Tregs) are a lymphocyte subset with intrinsic immunosuppressive properties that can be expanded in large numbers ex vivo and have been shown to prevent allograft rejection and promote tolerance in animal models. To investigate the safety, applicability, and biological activity of autologous Treg adoptive transfer in humans, we conducted an open-label, dose-escalation, Phase I clinical trial in liver transplantation. Patients were enrolled while awaiting liver transplantation or 6-12 months posttransplant.

Evoked Haptic Sensation in the Hand With Concurrent Non-Invasive Nerve Stimulation.

Objective: Haptic perception is critical for prosthetic users to control their prosthetic hand intuitively. In this study, we seek to evaluate the haptic perception evoked from concurrent stimulation trains through multiple channels using transcutaneous nerve stimulation.

Methods: A 2 × 8 electrode grid was used to deliver current to the median and ulnar nerves in the upper arm.

Allied health professionals in Queensland Health returning to work after maternity leave: hours of work and duration of time on part-time hours.

Objective The aim of this study was to provide a detailed description of the flexible working arrangements (FWA) used by allied health professionals (AHP) on return from maternity leave. This is a crucial issue for staff management practices in a changing regulatory context. Methods A retrospective convenience sample of AHP employed by Queensland Health (QH) in 2006, using deidentified payroll data, was analysed descriptively to determine employment status on return from maternity leave in 2006 to December 2014.

Multiparametric Analysis of Circulating Exosomes and Other Small Extracellular Vesicles by Advanced Imaging Flow Cytometry.

Extracellular vesicles (EVs) are responsible for a multitude of physiological functions, including immunomodulation. A heterogenous mixture of small EV (sEV) subsets, including putative exosomes, is derived when commonly used "exosome" isolation techniques are employed. Subset diversity relates in part to their different intracellular origins, and can be associated with distinct functional properties.

Entecavir or tenofovir monotherapy prevents HBV recurrence in liver transplant recipients: A 5-year follow-up study after hepatitis B immunoglobulin withdrawal.

Background: Recent data suggest that oral third-generation nucleos(t)ide analogs (NA) monoprophylaxis following hepatitis B immunoglobulin (HBIg) withdrawal may be effective to prevent HBV reinfection after liver transplantation (LT).

Patients And Methods: Between 01/2010 and 03/2012, all HBV monoinfected and HBV/HDV co-infected LT patients followed in our centre withdrew HBIg ± NA and were commenced on either ETV or TDF as monotherapy.

Results: Seventy-seven patients were included in the study (55% TDF, 45% ETV).

Protein supplements and adolescent athletes: A pilot study investigating the risk knowledge, motivations and prevalence of use.

Aim: Protein-based sports supplements are among the more common types of nutrition supplements consumed by athletes; however, there is currently limited data investigating the knowledge, motivations and occurrence of use among the adolescent population (13-18 years). This pilot study looks to obtain initial data regarding the use of protein supplements in this population.

Methods: This study investigates the understanding and occurrence of protein supplement use in 87 adolescent athletes based in an Australian capital city who compete in a variety of sports.

Regulatory T-cell therapy in liver transplantation.

Modern immunosuppression drug regimens have produced excellent short-term survival after liver transplantation but it is generally accepted that the side effects of these medications remain a significant contributing factor for less satisfactory long term outcomes. The liver has unique tolerogenic properties as evidenced by the higher rates of operational tolerance seen in liver transplant recipients compared to other solid organ transplants, and therefore, liver transplantation offers an attractive setting in which to study tolerizing therapies. CD4 CD25 FOXP3 regulatory T cells (Tregs) are crucial for maintenance of self-tolerance and prevention of autoimmune disease and are therefore an appealing potential candidate for use as a tolerizing cell therapy.

IL-2 therapy restores regulatory T-cell dysfunction induced by calcineurin inhibitors.

CD4CD25FOXP3 Tregs constitute a heterogeneous lymphocyte subpopulation essential for curtailing effector T cells and establishing peripheral tolerance. Calcineurin inhibitors (CNIs) are among the most effective agents in controlling effector T-cell responses in humans. However, CNIs also reduce the size of the Treg pool.

Successful expansion of functional and stable regulatory T cells for immunotherapy in liver transplantation.

Strategies to prevent organ transplant rejection whilst minimizing long-term immunosuppression are currently under intense investigation with regulatory T cells (Tregs) nearing clinical application. The clinical trial, ThRIL, recently commenced at King's College London, proposes to use Treg cell therapy to induce tolerance in liver transplant recipients, the success of which has the potential to revolutionize the management of these patients and enable a future of drug-free transplants. This is the first report of the manufacture of clinical grade Tregs from prospective liver transplant recipients via a CliniMACS-based GMP isolation technique and expanded using anti-CD3/CD28 beads, IL-2 and rapamycin.

Immunosuppression withdrawal following liver transplantation.

Current immunosuppression regimens in liver transplantation provide excellent short-term survival rates but have many deleterious long-term side effects. They are therefore associated with the higher mortality and morbidity seen in liver transplant recipients compared to the general population and the notion that many liver transplant recipients are over-immunosuppressed is widely accepted. Liver allografts show a greater resistance to alloimmune responses than other solid organ transplants and recent research suggests up to 60% of highly selected recipients could wean off immunosuppression completely.

The straight to test endoscopy service for suspected colorectal cancer: meeting national targets but are we meeting our patients' expectations?

Aim: The NHS Cancer Plan describes initiatives to improve patient care in the UK, including the two-week rule cancer referral pathway. To meet this target a straight to test (STT) endoscopy service was devised to expedite diagnosis of suspected colorectal cancer. Our novel study aimed to determine patient satisfaction with this new approach to rapid access investigation.

Prospective multicenter clinical trial of immunosuppressive drug withdrawal in stable adult liver transplant recipients.

Unlabelled: Lifelong immunosuppression increases morbidity and mortality in liver transplantation. Discontinuation of immunosuppressive drugs could lessen this burden, but the safety, applicability, and clinical outcomes of this strategy need to be carefully defined. We enrolled 102 stable liver recipients at least 3 years after transplantation in a single-arm multicenter immunosuppression withdrawal trial.

The effect of cataract on Accumap multifocal objective perimetry.

Purpose: To determine the effect of visually significant cataract on Accumap multifocal objective perimetry.

Design: Interventional case series.

Methods: Fifteen eyes of 15 adult patients who underwent standard outpatient phacoemulsification cataract surgery with posterior chamber intraocular lens insertion with subsequent improvement of best-corrected visual acuity underwent Accumap testing before and after cataract extraction.

The UK national study of magnetic resonance imaging as a method of screening for breast cancer (MARIBS).

The UK national study of magnetic resonance imaging as a method of screening for breast cancer (MARIBS) is in progress. The study design, accrual to date, and related research projects are described. Revised accrual rates and expected recruitment are given.

The rheumatoid cervical spine: signs of instability on plain cervical radiographs.

The cervical spine is a common focus of destruction from rheumatoid arthritis, second only to the metacarpophalangeal joints. Joint, bone and ligament damage in the cervical spine leads to subluxations which can cause cervical cord compression resulting in paralysis and even sudden death. Because many patients with significant subluxations are asymptomatic, the radiologist plays a key role in recognizing the clinically important clues to instability on plain radiographs of the cervical spine-often difficult in rheumatoid arthritis when the bony landmarks are osteoporotic or eroded.

A proton magnetic resonance spectroscopy study of age-related changes in frontal lobe metabolite concentrations.

Ageing is associated with reduction of grey matter volume and it is reported that the frontal lobes are preferentially affected. We have applied quantitative magnetic resonance spectroscopy (MRS), incorporating measurement of brain tissue water content and metabolite T(2) relaxation times, to determine absolute concentrations of the putative neuronal marker N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) compounds in the frontal lobe of 50 male subjects aged between 20 and 70 years (10 per decade). The fractional brain water content (beta(MR)) did not change significantly as a function of age (r = 0.

Quantitative magnetic resonance imaging in consecutive patients evaluated for surgical treatment of temporal lobe epilepsy.

We present the results of quantitative Magnetic Resonance Imaging (MRI) in 55 consecutively referred patients with clinical evidence of temporal lobe epilepsy (TLE). The Cavalieri method was used in combination with point counting to provide unbiased estimates of the volume of the left and right hippocampus, amygdala, temporal lobe, lateral ventricles and cerebral hemisphere, and pixel by pixel maps of the T2 relaxation time were computed for both central and anterior sections of the hippocampus. The 99th centiles of hippocampal volume, hippocampal volume asymmetry and T2 relaxation times in 20 control subjects provided limits which identified the presence of MTS.