Background: There are no clinical or laboratory markers that can diagnose acute mesenteric ischemia (AMI) accurately. This study aimed to find differences in clinical and laboratory markers between arterial occlusive AMI and other acute abdominal diseases where AMI was initially suspected.
Methods: This was a post hoc study of an international prospective multicenter study where data on patients with suspected AMI were collected.
Lead isotopes are a powerful geochemical tracer and a popular tool applied across a broad range of scientific fields, e.g., earth sciences, archaeology, and forensic sciences.
View Article and Find Full Text PDFBackground: Subarachnoid hemorrhage (SAH) is a devastating disease with high morbidity and mortality. Neuroprotective effects of the noble gas argon have been shown in animal models of ischemia. The aim of this study was to investigate the effects of argon in the immediate early phase of SAH in a rat model.
View Article and Find Full Text PDFThe liver has a unique ability to regenerate; however, in the setting of acute liver failure (ALF), this regenerative capacity is often overwhelmed, leaving emergency liver transplantation as the only curative option. Here, to advance understanding of human liver regeneration, we use paired single-nucleus RNA sequencing combined with spatial profiling of healthy and ALF explant human livers to generate a single-cell, pan-lineage atlas of human liver regeneration. We uncover a novel ANXA2 migratory hepatocyte subpopulation, which emerges during human liver regeneration, and a corollary subpopulation in a mouse model of acetaminophen (APAP)-induced liver regeneration.
View Article and Find Full Text PDFUnlabelled: Defining the initial events in oncogenesis and the cellular responses they entrain, even in advance of morphologic abnormality, is a fundamental challenge in understanding cancer initiation. As a paradigm to address this, we longitudinally studied the changes induced by loss of the tumor suppressor gene von Hippel Lindau (VHL), which ultimately drives clear cell renal cell carcinoma. Vhl inactivation was directly coupled to expression of a tdTomato reporter within a single allele, allowing accurate visualization of affected cells in their native context and retrieval from the kidney for single-cell RNA sequencing.
View Article and Find Full Text PDFBackground: The aim of this multicentre prospective observational study was to identify the incidence, patient characteristics, diagnostic pathway, management and outcome of acute mesenteric ischaemia (AMI).
Methods: All adult patients with clinical suspicion of AMI admitted or transferred to 32 participating hospitals from 06.06.
Periprosthetic joint infection (PJI) after shoulder arthroplasty remains a significant complication. This study aimed to explore the epidemiology and risk factors of shoulder PJI in patients aged 60 and younger, analyze treatment options, and evaluate outcomes after 1-year follow-up. In this retrospective multicentric observational study, data from 1404 shoulders in patients under 60 who underwent primary shoulder arthroplasty were analyzed.
View Article and Find Full Text PDFLiver biopsy remains the gold standard for the histological assessment of the liver. With clear disadvantages and the rise in the incidences of liver disease, the role of neoadjuvant chemotherapy in colorectal liver metastasis (CRLM) and an explosion of surgical management options available, non-invasive serological and imaging markers of liver histopathology have never been more pertinent in order to assess liver health and stratify patients considered for surgical intervention. Liver MRI is a leading modality in the assessment of hepatic malignancy.
View Article and Find Full Text PDFImportance: Considering the lack of equipoise regarding the timing of cholecystectomy in patients with moderately severe and severe acute biliary pancreatitis (ABP), it is critical to assess this issue.
Objective: To assess the outcomes of early cholecystectomy (EC) in patients with moderately severe and severe ABP.
Design, Settings, And Participants: This cohort study retrospectively analyzed real-life data from the MANCTRA-1 (Compliance With Evidence-Based Clinical Guidelines in the Management of Acute Biliary Pancreatitis) data set, assessing 5304 consecutive patients hospitalized between January 1, 2019, and December 31, 2020, for ABP from 42 countries.
Background: Posthepatectomy liver failure (PHLF) contributes significantly to morbidity and mortality after liver surgery. Standardized assessment of preoperative liver function is crucial to identify patients at risk. These European consensus guidelines provide guidance for preoperative patient assessment.
View Article and Find Full Text PDFKynurenine monooxygenase (KMO) blockade protects against multiple organ failure caused by acute pancreatitis (AP), but the link between KMO and systemic inflammation has eluded discovery until now. Here, we show that the KMO product 3-hydroxykynurenine primes innate immune signaling to exacerbate systemic inflammation during experimental AP. We find a tissue-specific role for KMO, where mice lacking Kmo solely in hepatocytes have elevated plasma 3-hydroxykynurenine levels that prime inflammatory gene transcription.
View Article and Find Full Text PDFObjective: To generate an up-to-date bundle to manage acute biliary pancreatitis using an evidence-based, artificial intelligence (AI)-assisted GRADE method.
Background: A care bundle is a set of core elements of care that are distilled from the most solid evidence-based practice guidelines and recommendations.
Methods: The research questions were addressed in this bundle following the PICO criteria.
Circadian rhythms are responsible for governing various physiological processes, including hormone secretion, immune responses, metabolism, and the sleep/wake cycle. In critical illnesses such as acute pancreatitis (AP), circadian rhythms can become dysregulated due to disease. Evidence suggests that time of onset of disease, coupled with peripheral inflammation brought about by AP will impact on the circadian rhythms generated in the central pacemaker and peripheral tissues.
View Article and Find Full Text PDFHypoxia-inducible factor (HIF) and aryl hydrocarbon receptor (AHR) are members of the bHLH-PAS family of transcription factors that underpin cellular responses to oxygen and to endogenous and exogenous ligands, respectively, and have central roles in the pathogenesis of renal cancer. Composed of heterodimers, they share a common HIF-1β/ARNT subunit and similar DNA-binding motifs, raising the possibility of crosstalk between the two transcriptional pathways. Here, we identify both general and locus-specific mechanisms of interaction between HIF and AHR that act both antagonistically and cooperatively.
View Article and Find Full Text PDFActivation of cellular hypoxia pathways, orchestrated by HIF (hypoxia-inducible factor) transcription factors, is a common feature of multiple tumor types, resulting from microenvironment factors and oncogenic mutation. Although they help drive many of the "hallmarks" of cancer and are associated with poor outcome and resistance to therapy, the transcriptional targets of HIF vary considerably depending on the cell type. By integrating 72 genome-wide assays of HIF binding and transcriptional regulation from multiple cancer types, we define a consensus set of 48 HIF target genes that is highly conserved across cancer types and cell lineages.
View Article and Find Full Text PDFBackground: In vitro data demonstrate the potential benefits of the pyrocarbon as a bearing material against cartilage or bone. And pyrocarbon-free interposition arthroplasty has been used with positive outcomes for over 10 years for hand and wrist joint replacements. This study reports the midterm results of a Pyrocarbon Interposition Shoulder Arthroplasty (PISA) in primary and secondary glenohumeral osteoarthritis and in avascular osteonecrosis.
View Article and Find Full Text PDFBackground/objectives: Reports about the implementation of recommendations from acute pancreatitis guidelines are scant. This study aimed to evaluate, on a patient-data basis, the contemporary practice patterns of management of biliary acute pancreatitis and to compare these practices with the recommendations by the most updated guidelines.
Methods: All consecutive patients admitted to any of the 150 participating general surgery (GS), hepatopancreatobiliary surgery (HPB), internal medicine (IM) and gastroenterology (GA) departments with a diagnosis of biliary acute pancreatitis between 01/01/2019 and 31/12/2020 were included in the study.
Impaired glucocorticoid (GC) signaling is a significant factor in aging, stress, and neurodegenerative diseases such as Alzheimer's disease. Therefore, the study of GC-mediated stress responses to chronic moderately stressful situations, which occur in daily life, is of huge interest for the design of pharmacological strategies toward the prevention of neurodegeneration. To address this issue, SAMP8 mice were exposed to the chronic mild stress (CMS) paradigm for 4 weeks and treated with RL-118, an 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor.
View Article and Find Full Text PDFOur study investigated the underlying mechanism for the 14q24 renal cell carcinoma (RCC) susceptibility risk locus identified by a genome-wide association study (GWAS). The sentinel single-nucleotide polymorphism (SNP), rs4903064, at 14q24 confers an allele-specific effect on expression of the double PHD fingers 3 (DPF3) of the BAF SWI/SNF complex as assessed by massively parallel reporter assay, confirmatory luciferase assays, and eQTL analyses. Overexpression of DPF3 in renal cell lines increases growth rates and alters chromatin accessibility and gene expression, leading to inhibition of apoptosis and activation of oncogenic pathways.
View Article and Find Full Text PDFHypoxia-inducible transcription factors (HIFs) are fundamental to cellular adaptation to low oxygen levels, but it is unclear how they interact with chromatin and activate their target genes. Here, we use genome-wide mutagenesis to identify genes involved in HIF transcriptional activity, and define a requirement for the histone H3 lysine 4 (H3K4) methyltransferase SET1B. SET1B loss leads to a selective reduction in transcriptional activation of HIF target genes, resulting in impaired cell growth, angiogenesis and tumor establishment in SET1B-deficient xenografts.
View Article and Find Full Text PDFMuch of the current volume of Earth's continental crust had formed by the end of the Archaean eon (2.5 billion years ago), through melting of hydrated basaltic rocks at depths of approximately 25-50 kilometres, forming sodic granites of the tonalite-trondhjemite-granodiorite (TTG) suite. However, the geodynamic setting and processes involved are debated, with fundamental questions arising, such as how and from where the required water was added to deep-crustal TTG source regions.
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