The Glasgow Royal Infirmary (GRI) is a large teaching hospital. With a capacity of around 1,000 beds, the hospital campus covers an area of around 8 hectares (20 acres), situated on the north-eastern edge of the city centre of Glasgow, Scotland. It is managed by NHS Greater Glasgow and Clyde. It was originally opened in 1794, with the present main building dating from 1914.
This systematic review and meta-analysis are aimed at evaluating the incidence of adverse drug reactions (ADRs) following administration of clinically approved ultrasound contrast agents (UCAs) in adults and children, to assess risks in patients with cardiovascular disease and in pregnancy, and to evaluate the effectiveness of emergency management of severe ADRs. A PRISMA 2020 systematic review was conducted searching PubMed, Scopus, and Embase. Two reviewers independently screened, extracted data, and assessed quality. Incidence estimates were pooled when feasible, stratified by age group, contrast agent, and administration route. Seventy-four studies encompassing > 1 million adults and > 36,000 children were included, contributing multiple analytic cohorts to the quantitative synthesis. Severe acute ADRs were extremely rare (6 and 16 cases per 100,000 in adults and children, respectively) and absent following endocavitary administration in children. Non-severe acute ADRs occurred in 11 and 8 cases per 10,000 adults and children, respectively. Delayed reactions were very rare (< 1 case per million in adults). No significant safety differences emerged between UCA products. The incidence of ADRs in patients with cardiovascular disease was analogous to the general population. No ADRs were reported in pregnant women. Standard emergency management was effective in almost all serious cases, though rare fatalities occurred. UCAs show an excellent safety profile in adults and children, with very rare severe ADRs and few non-severe, typically self-limiting reactions. Strict adherence to recommended emergency management protocols mitigates the remaining risks, supporting safe use across a broad range of clinical indications. CRD42023432668. Question What is the incidence, type, and severity of acute and delayed ADRs associated with clinically approved UCAs across different patient populations? Findings Severe acute adverse reactions are very rare, and non-severe reactions are rare and self-limiting, with no significant safety differences between adults, children, or patients with cardiovascular disease. Clinical relevant UCAs show an excellent safety profile across populations. These findings support their safe clinical use as reliable alternatives to iodine-based and gadolinium-based contrast agents in routine diagnostic imaging.
Intraductal papillary mucinous neoplasms (IPMNs) are critical precursors to pancreatic ductal adenocarcinoma, a highly lethal cancer characterized by late detection and rapid progression. Here we integrate multi-region whole-genome and transcriptome sequencing to trace the evolution of IPMN, constructing detailed phylogenetic trees to provide insights into subclonal architectures and progression pathways. Our analysis identifies two distinct evolutionary trajectories: one driven by a single ancestral clone, and another involving multiple independent ancestral clones. We further explore the roles of mutational signatures and structural variants in promoting clonal evolution and the emergence of new subclones. Complementing these genomic findings, our transcriptomic analysis reveals unique gene expression profiles and variations in the immune landscape that correlate with different progression stages of IPMN. These insights reveal the complex molecular dynamics of IPMN heterogeneity and progression, highlighting the need to refine early detection and treatment strategies.
Liver cirrhosis is a major contributor to global morbidity and mortality, and transplantation remains the only cure for end-stage disease. Preclinical studies have indicated that macrophage injections reduce inflammation, resolve fibrosis, and stimulate liver regeneration. The phase 1/2 Macrophage Therapy for Liver Cirrhosis trial (MATCH01; ISRCTN10368050) demonstrated the safety and potential efficacy of autologous monocyte-derived macrophage therapy in cirrhosis. Following MATCH01, participants were re-enrolled in a long-term follow-up (LTFU) study, extending observation to up to 4 years from randomization. Macrophage-treated patients in MATCH01 phase 2 demonstrated a significantly lower risk of death or transplant within the LTFU period (30.8%) compared with standard medical care (58.3%); macrophage-treated patients had an additional 252 days of restricted mean survival time within the LTFU period. There was no evidence of increased serious adverse events attributable to cell therapy. These results support the continued advancement of macrophage-based regenerative strategies as a promising therapeutic option for end-stage liver disease.
OBJECTIVES:We sought to evaluate the comparative activity of rezafungin compared with caspofungin and other antifungal classes against biofilms from a large clinical panel of Candida strains (n = 167). METHODS:Biofilm killing and inhibition were assessed using standard XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide salt] metabolic assessment. Biofilm time-kill kinetics were also evaluated using metabolic and viable cell counts. Microscopy was performed to visually assess biofilm inhibition. RESULTS:Rezafungin was shown to outperform caspofungin and other antifungals against C. albicans, C. parapsilosis, C. tropicalis and Nakaseomyces glabratus (previously called C. glabrata) strains with a heterogeneous biofilm phenotype. Assessment of high biofilm-forming strains at 0.03 mg/L concentrations showed that rezafungin killed biofilms to an equal or greater extent than caspofungin. Time-kill studies showed a rapid reduction in metabolism and viable cfus by both rezafungin and caspofungin, but with little difference between both compounds. Evaluation of biofilm inhibition characteristics of both compounds showed that rezafungin was marginally more effective than caspofungin, which was corroborated by microscopical analyses. CONCLUSIONS:Together, these data show that rezafungin is non-inferior to caspofungin in terms of anti-biofilm activity and displays characteristics that suggest it can control biofilms more effectively than caspofungin. Further evaluation is required to establish whether these in vitro effects translate clinically, but the data indicate an opportunity for rezafungin to be used for the clinical management of biofilm-related diseases.
