St Mary's Hospital

The effects of aspirin on hepatic steatosis and fibroinflammation are unclear. The study aimed to examine the association between aspirin use and liver magnetic resonance imaging (MRI)-derived liver fat and corrected T1 (cT1). We used UK Biobank imaging cohort data. Aspirin use was self-reported at baseline and imaging assessment, and the main exposures were aspirin use at imaging assessment and longitudinal aspirin use patterns (never users, initiators, discontinuers, vs. persistent users). Outcomes were MRI-derived liver fat (%) and cT1 (ms). Multivariable adjustment analyses and inverse probability of treatment weighting (IPTW) analyses were performed, accounting for demographic, lifestyle and clinical factors. We included 36 413 participants (mean age 64.6 years, 51.4% female). Aspirin use at imaging assessment was associated with lower liver fat (-0.35; 95% confidence interval [CI]: -0.51, -0.20) and slightly higher cT1 (5.13; 95% CI: 3.23, 7.03). Analyses on longitudinal aspirin use patterns showed that compared to never users, initiators and persistent users showed lower liver fat (-0.48; -0.69, -0.28) and (-0.24; -0.45, -0.02) and higher cT1 (2.94; 0.38, 5.49) and (8.31; 5.65, 10.97). IPTW analyses showed consistent results. In this large population-based cohort, aspirin use was linked to reduced liver fat, but a small, clinically insignificant (i.e., <80 ms) increase in cT1. These findings suggest aspirin may mitigate steatosis through metabolic pathways but does not necessarily rapidly reverse fibroinflammatory injury.

RASopathies are clinically overlapping neurodevelopmental syndromes resulting from germline mutations in genes involved in the rat sarcoma/mitogen-activated protein kinases (RAS/MAPK) pathway. Historically, RASopathies have been described by clinical phenotypes, such as Noonan syndrome and Neurofibromatosis type I. There is emerging evidence of the association between Noonan syndrome spectrum disorders (NSSD) and systemic lupus erythematosus (SLE). Here, we present an SLE patient diagnosed with SOS1-associated Noonan Syndrome (c.806 T>C; p.Met269Thr) as part of a research study. Reviewing the literature, we identified further 16 cases of NSSD associated with SLE. Nine out of 16 cases (56%) had a confirmed molecular diagnosis, with pathogenic missense variants identified in KRAS, PTPN11, and SHOC2 genes, the majority in the last. Variants in SHOC2 are the cause of only a small proportion of all presentations of NSSD. Our case represents the first reported case of SLE in a patient with a SOS1 pathogenic variant. Compared to the general SLE population, SLE in the presence of NSSD develops at a younger age, with a similar prevalence among females and males, suggesting a contribution of the RAS/MAPK pathway in the development of SLE.

Background: Generative artificial intelligence (GenAI) is rapidly permeating healthcare; yet, U.S. clinicians still report mixed feelings about its reliability, impact on workflow, and ethical implications. Current data on provider sentiment are needed to guide safe, patient-centered AI implementation in healthcare. Objective: This study aimed to assess U.S. healthcare providers' perceptions of generative AI adoption, perceived usefulness, training needs, barriers, and strategies for safe integration. Methods: A nationwide, IRB-approved, cross-sectional survey was administered to healthcare professionals using Qualtrics. A convenience sample of clinicians was recruited via professional listservs and e-mail invitations. The 20-page questionnaire captured demographics, GenAI exposure, organizational adoption status, perceived usefulness (5-point scale), barriers, and mitigation strategies. SPSS v27 and Microsoft Excel were used for statistical analysis. Results: Of 130 respondents, 109 completed the core survey (completion rate 83.8%). Participants were 38.5% physicians, 16.5% nurses, 12.8% allied professionals, and 32.2% other providers; 54.2% were women, and 64.8% were ≥50 years. Overall, 86.9% agreed that GenAI is useful in current patient care, rising to 92.9% when asked about future usefulness. Only 42.4% had received formal GenAI training, and just 23.2% reported that their organization had begun adopting AI. The top perceived benefits were improved documentation/clerking (57.0%) and error reduction (49.4%). Dominant barriers included limited AI knowledge (24.7%) and fear of job loss (16.9%). Despite concerns, 72% expressed willingness to support broader GenAI adoption, favoring human oversight (67.1%) and staff training (60.8%) as key safeguards. There were statistically significant findings in perceived AI usefulness by gender (χ2 = 29.2; p < 0.001); organizational adoption of AI (χ2 = 31.6.2; p = 0.047) and where AI is most useful (χ2 = 101.1; p < 0.001) by qualifications; and support for AI adoption by age (χ2 = 18.0; p = 0.02). Conclusions: U.S. clinicians in our survey viewed GenAI as useful but reported limited training and organizational infrastructure needed for confident use while also expressing concerns regarding data privacy and ethical risk. Education programs and transparent, provider-led implementation strategies may accelerate responsible GenAI assimilation while addressing ethical and workforce concerns. Also, health administrators should use the efficiency gains to improve provider-patient relationships and clinicians' work-life balance while reducing clinician burnout rates.

Pharmacogenomic (PGx) information has the potential to support the safe and effective use of medicines, yet there is uncertainty about how this information can be best communicated to patients. Summaries of product characteristics (SmPCs) and patient information leaflets (PILs) for all UK-approved medicines with strong evidence supporting a PGx prescribing recommendation (CPIC Levels A or provisional A/B) were reviewed, using keyword searches to identify relevant content and estimating the reading age of PGx information in PILs using the Flesch-Kincaid grade level. Among 353 products, 281 (80%) SmPCs contained PGx information, but this was reflected in only 115 (33%) PILs. Where present, the PGx content in PILs required an average reading age of 19.1 years, far exceeding the typical UK reading age of 9-11 years. As the availability of genomic data becomes increasingly routine, the variable PGx information provided in PILs risks undermining patient understanding, engagement and safe personalized prescribing.

Varicella zoster virus (VZV) vasculopathy is a rare but severe neurological complication that frequently results in a reversible cerebral vasoconstriction syndrome (RCVS). Diagnosis is often delayed because early manifestations are nonspecific and radiologic findings often overlap with those of other cerebrovascular disorders. We describe the fatal case of a heavily pretreated 60-year-old man with refractory diffuse large B-cell lymphoma undergoing evaluation for chimeric antigen receptor (CAR) T-cell therapy. The patient developed multifocal intracranial arterial stenosis and an acute infarction during chemotherapy-induced immunosuppression. The initial radiological features suggested RCVS; however, cerebrospinal fluid (CSF) analysis using polymerase chain reaction (PCR) and anti-IgG antibodies confirmed the presence of VZV. Despite intravenous acyclovir and high-dose corticosteroids, the vasculopathy progressed rapidly, resulting in recurrent infarctions, seizures, and death. This case highlights the diagnostic complexity of VZV vasculopathy in immunocompromised patients and underscores the importance of early CSF evaluation, heightened clinical vigilance for opportunistic viral complications, and the potential diagnostic value of vessel wall magnetic resonance imaging (MRI) in differentiating VZV vasculopathy from mimicking conditions such as RCVS.

Low-grade B-cell lymphomas (LGBCLs) account for approximately 40% of non-Hodgkin lymphomas with low progression. LGBCL is divided into subgroups, which share common complications. Analyzing prognostic factors and mortality causes could improve patient survival; however, currently available models present limitations in discriminating the cause of death. Therefore, this study aimed to compare the prognostic factors and causes of death, such as secondary malignancies (SMs), aggressive histologic transformation (HT), and infectious complications, including coronavirus disease 2019 (COVID-19), in LGBCLs using a competing risk analysis. This retrospective analysis included 1,047 adults with LGBCLs (follicular lymphoma, 689; marginal zone lymphoma, 312; mantle cell lymphoma [MCL], 46) diagnosed between January 2011 and December 2022 across seven centers. Competing risk models were employed to estimate cumulative incidence rates of lymphoma progression-related and non-lymphoma-related mortality. Patients with SMs (3.8%) exhibited poorer overall survival than those without SMs, whereas HT and COVID-19 status did not impact survival outcomes in multivariate analysis. Analysis revealed an association of SMs, age > 60 years, male sex, pleural effusion, and elevated lactate dehydrogenase levels with worse non-lymphoma-related mortality. Moreover, age > 60 years, MCL, nodal MZL, and anemia were linked to poorer outcomes for lymphoma progression-related death. The management of non-lymphoma-related risk factors, such as through early SM detection, is crucial for improving the survival of patients with LGBCLs.

Biallelic hypomorphic variants in PRORP cause the rare autosomal recessive disorder combined oxidative phosphorylation deficiency type 54 (COXPD54). COXPD54 encompasses a clinical spectrum of sensorineural hearing loss and ovarian insufficiency (Perrault syndrome) to leukodystrophy with developmental delay and epilepsy. Here, we report two new affected individuals with biallelic PRORP variants with clinical features consistent with COXPD54. One individual was homozygous for c.1505G > A p.Arg502Gln, whereas the other was compound heterozygous for c.1510C > T, p.His504Tyr and c.893C > A, p.Ser298Ter (NM_014672.4). In vitro tRNA processing assays revealed decreased mitochondrial 5′ tRNA leader cleavage by human RNase P complex with the two novel missense PRORP metallonuclease domain variants. These data provide further evidence that biallelic PRORP variants disrupt 5’ tRNA leader cleavage and are associated with a pleiotropic phenotype of COXPD54.

Fecal microbiota transplantation (FMT) is effective for recurrent Clostridioides difficile infection (rCDI). Adverse reactions to FMT occur early, and cellular immune responses after FMT may contribute to effects and reactions. We compared early changes in peripheral immune cell subsets and clinical outcomes in patients with rCDI who received either FMT and antibiotics or antibiotics alone in a randomized trial. Thirty-five patients with rCDI were randomized to vancomycin and FMT (n = 20) or vancomycin alone (n = 15). Blood samples were drawn before (wk0) and 1 week (wk1) after treatment. In 3 additional patients, blood samples were drawn before and 24 hours and wk1 after FMT. Adaptive and innate immune cell subsets and gut-homing memory (CD45RO + integrinβ7 + ) and effector (CD45RO - integrinβ7 + ) T cells were analyzed by flow cytometry. FMT induced subtle changes in immune cell subsets with no clear pattern from wk0 to wk1. The Treg fraction tended to decrease after FMT, and a similar decrease at 24 hours indicated rapid T regulatory cells dynamics. Natural killer T (NKT) cells increased during the first 24 hours and returned to baseline level at wk1. Regardless of FMT, patients with clinical resolution from rCDI had a decrease in nonclassical monocytes and a shift in gut-homing memory to effector cells at wk1. In rCDI, FMT induced subtle and transient dynamics in peripheral immune cell subsets. T regulatory cells and NKT cells seemed responsive and should be further studied. Cure of Clostridioides difficile infection may be associated with an increase in circulating gut-homing T cells.