Acute liver failure is a rapidly progressing, life-threatening condition most commonly caused by an overdose of acetaminophen (paracetamol). The antidote, N-acetylcysteine (NAC), has limited efficacy when liver injury is established. If acute liver damage is severe, liver failure can rapidly develop with associated high mortality rates.
View Article and Find Full Text PDFGiven the lack of accurate diagnostic methods of acetaminophen (APAP)-induced acute liver failure (ALF), the search for new biomarkers for its diagnosis is an urgent need. The aim of this study was to evaluate the role of bone morphogenetic protein 6 (BMP6) in APAP-induced ALF progression and its potential value as a biomarker of ALF. Hepatic and circulating BMP6 expression was assessed in APAP-treated mice and in serum samples from patients with APAP overdose.
View Article and Find Full Text PDFSjogren's disease, well-described in people, is rarely identified in veterinary species. In people, Sjogren's disease is one of the most common systemic autoimmune disorders with an incidence of 0.5% in the female population.
View Article and Find Full Text PDFIntroduction: Acute liver failure (ALF) has no effective treatment other than liver transplantation and is commonly caused by paracetamol overdose. New treatments are needed to treat and prevent ALF. Alternatively-activated macrophages (AAMs) can promote resolution of liver necrosis and stimulate hepatocyte proliferation.
View Article and Find Full Text PDFAcute liver injury (ALI) has a clear requirement for novel therapies. One emerging option is the use of alternatively activated macrophages (AAMs); a distinct subtype of macrophage with a role in liver injury control and repair. In this comprehensive review, we provide an overview of the current limited options for ALI, and the potential advantages offered by AAMs.
View Article and Find Full Text PDFBackground: Recurrent bacterial cystitis, often referred to as recurrent urinary tract infection (UTI), can be difficult to manage and alternative treatments are needed.
Hypothesis/objective: Intravesicular administration of asymptomatic bacteriuria (ASB) E. coli 212 will not be inferior to antimicrobial treatment for the management of recurrent UTI in dogs.
Introduction: Paracetamol (acetaminophen) overdose is a leading cause of acute liver failure in many Western countries. Diagnostic tools for this poisoning may be suboptimal in some cases and new biomarkers have been investigated. We investigated the role of capillary microRNA-122 (miR-122) as a prognostic biomarker of liver injury in the clinical management of patients with paracetamol overdose.
View Article and Find Full Text PDFDrug-induced liver injury (DILI) is a challenge in clinical medicine and drug development. Highly sensitive novel biomarkers have been identified for detecting DILI following a paracetamol overdose. The study objective was to evaluate biomarker performance in a 14-day trial of therapeutic dose paracetamol.
View Article and Find Full Text PDFBackground: Pancreatitis is an important cause of disease and death in dogs. Available circulating biomarkers are not sufficiently sensitive and specific for a definitive diagnosis.
Hypothesis: Circulating microRNAs would be differentially expressed in dogs with chronic pancreatitis and could have potential as diagnostic biomarkers.
Introduction: Fifty years ago, basic scientific studies and the availability of assay methods made the assessment of risk in paracetamol (acetaminophen) poisoning possible. The use of the antidote acetylcysteine linked to new methods of risk assessment transformed the treatment of this poisoning. This review will describe the way in which risk assessment and treatments have developed over the last 50 years and highlight the remaining areas of uncertainty.
View Article and Find Full Text PDFspecies infect a very wide range of mammal hosts across the globe, and zoonotic infections are of growing concern. Several species of the genus infect dogs, and some of these cause significant morbidity and mortality. The Apicomplexan parasite resides within the red cell and infections result in direct damage to the host through intra- and extravascular hemolysis.
View Article and Find Full Text PDFIn patients with chronic kidney disease (CKD), there is an unmet need for novel biomarkers that reliably track kidney injury, demonstrate treatment-response, and predict outcomes. Here, we investigate the potential of retinal optical coherence tomography (OCT) to achieve these ends in a series of prospective studies of patients with pre-dialysis CKD (including those with a kidney transplant), patients with kidney failure undergoing kidney transplantation, living kidney donors, and healthy volunteers. Compared to health, we observe similar retinal thinning and reduced macular volume in patients with CKD and in those with a kidney transplant.
View Article and Find Full Text PDFBackground: Polyautoimmunity is the expression of more than one autoimmune disease in a single patient. This report documents polyautoimmunity in a mixed breed dog with concurrent uveitis, cutaneous depigmentation, and inflammatory myopathy.
Case Presentation: A 1-year-old male neutered mixed breed dog was presented for progressive generalized leukotrichia and leukoderma, bilateral panuveitis, and masticatory muscle atrophy.
Background: The prevalence, prediction and impact of acute kidney injury (AKI) in alcohol-related hepatitis (AH) is uncertain.
Aims: We aimed to determine AKI incidence; association with mortality; evaluate serum biomarkers and the modifying effects of prednisolone and pentoxifylline in the largest AH cohort to date.
Methods: Participants in the Steroids or Pentoxifylline for Alcoholic Hepatitis trial with day zero (D0) creatinine available were included.
Background: The effect of the duration of consultant experience on clinical outcomes in the acute medical unit (AMU) model remains unknown.
Methods: Unscheduled AMU admissions (n=66,929) admitted by 56 consultant physicians between 2017 and 2020 to two large teaching hospital AMUs in Lothian, Scotland were examined. The associations of consultant experience on AMU with patient discharge, mortality, readmission and postdischarge death were calculated adjusting for clinical acuity, pathology and comorbidity.
Introduction: Liver toxicity due to medicines (drug-induced liver injury) is a challenge for clinicians and drug developers. There are well-established biomarkers of drug-induced liver injury, which are widely used and validated by decades of clinical experience. These include alanine aminotransferase and bilirubin.
View Article and Find Full Text PDFIntroduction: Acetylcysteine is the only effective and licensed therapy for paracetamol poisoning. However, acetylcysteine loses efficacy if treatment is delayed 8-12 hours after paracetamol ingestion, and there is also uncertainty as to whether the dose should be increased in high-risk paracetamol ingestions. Studies have identified potential therapeutic targets, including enzymes that metabolize paracetamol; the pathways causing mitochondrial toxicity c-Jun N-terminal kinases or superoxide generation; and other specific targets, such as nuclear factor-erythroid factor 2-dependent gene induction and autophagy.
View Article and Find Full Text PDFAims: A key reason for the failure of antituberculosis (anti-TB) treatment is missed doses (instances where medication is not taken). Adverse drug reactions (ADRs) are 1 cause of missed doses, but the global evidence, their relative contribution to missed doses vs. other causes, the patterns of missed doses due to ADRs and the specific ADRs associated with missed doses have not been appraised.
View Article and Find Full Text PDFA 10-year-old, female spayed Labrador Retriever was referred for acute hepatopathy and urinary retention. Blood work from the initial presentation (day 0) revealed a severe, mixed hepatopathy. Over the course of the patient's hospitalization, the patient developed liver insufficiency.
View Article and Find Full Text PDFBackground: Awareness of prescribing practices helps identify opportunities to improve antibiotic use (AU).
Objectives: To estimate AU prevalence in dogs and cats in U.S.
Background: Amphotericin-B (AmB) is an essential medication for the treatment of life-threatening systemic mycoses but the incidence and risk factors for acute kidney injury (AKI) after its administration are not known in dogs.
Objective: Determine the incidence of and risk factors for AKI in dogs receiving AmB.
Animals: Fifty-one client owned dogs receiving AmB for the treatment of systemic mycoses.
Background: The ability to detect bacteriuria in dogs with a point-of-care test might improve medical care and antimicrobial stewardship.
Hypothesis And Objective: A rapid immunoassay (RIA; RapidBac) will provide acceptable sensitivity and specificity for diagnosis of bacteriuria.
Animals: Forty-four client-owned dogs with a clinical indication for urinalysis and aerobic bacterial urine culture.