Citations

Spinocerebellar ataxia type 7 (SCA7), a rare form of ataxia, possesses a wide phenotypic spectrum ranging from classic ataxic symptoms to blindness, multiorgan failure, cardiomyopathy, and early death among younger age groups. Biomarkers associated with disease progression and severity could aid in disease prognostication. We evaluated the utility of glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) in distinguishing patients with SCA7 from healthy controls and estimating patient prognosis. GFAP and NfL levels were measured in 23 plasma and 20 cerebrospinal fluid (CSF) samples from asymptomatic (N = 3) and symptomatic SCA7 participants (N = 10) and from healthy controls (N = 8). GFAP concentrations were elevated in the plasma (82.7 pg/mL) and CSF (9318 pg/mL) of patients with SCA7 compared to controls (plasma: 48.0 pg/mL; CSF: 89,056 pg/mL). Similarly, NfL plasma (21.6 pg/mL) and CSF (2615.0 pg/mL) levels were also significantly upregulated in SCA7 compared to controls (plasma: 8.2 pg/mL; CSF: 414.6 pg/mL). Higher levels of NfL, but not of GFAP, significantly discriminated symptomatic SCA7 patients from controls (area under de curve, AUC: 0.898, p = 0.0059, in plasma, and AUC: 1.0, p = 0.0012, in CSF). The levels of both biomarkers increased overtime, with plasma NfL levels strongly associated with a worse score in the scale for the assessment and rating of ataxia (SARA) (Spearman r: 0.8354, p = 0.0007; regression analysis: β: 0.021, 95% CI: 0.008–0.035, p = 0.0048). These findings suggest that NfL could serve as a valuable biomarker for monitoring disease progression and prognosis in SCA7 patients.

This review examines the applications and challenges of large language models (LLMs), like OpenAI’s ChatGPT, in radiology research. ChatGPT can assist radiology researchers in generating new ideas, finding and summarizing research papers, designing studies, analyzing data, and facilitating manuscript writing. LLMs are powerful tools with numerous applications in radiology research. However, users should be mindful of potential pitfalls, such as producing incorrect or biased outputs and inconsistent responses, along with ethical and privacy concerns. We discuss approaches to optimize models and address these issues, including prompting techniques like chain-of-thought prompting, retrieval-augmented generation, and fine-tuning. For researchers, prompt engineering can be particularly effective. This review seeks to demonstrate how researchers can utilize ChatGPT for radiology research while offering strategies to mitigate associated risks. We aim to help researchers harness these potent tools to safely boost their productivity.

Abstract This retrospective analysis aimed to provide evidence-based risk stratification of TP53-mutated (TP53mut) myeloid neoplasms (MNs). Of 580 MNs harboring TP53mut with variant allele frequency (VAF) ≥2%, 219 (37.8%), 194 (33.4%), 92 (15.9%), and 75 (12.9%) were classified as acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) with low blasts (MDS-LB), MDS with excess blasts (MDS-EB)-2, and -EB1 according to the revised fourth edition of the World Health Organization (WHO) classification, respectively. Hierarchical analysis identified the following 4 risk groups with distinct survival: (1) MDS-LB, (2) MDS-EB1/EB2/AML VAF <10%, (3) MDS-EB1/EB2 VAF ≥10%, and (4) AML VAF ≥10%. We next evaluated the impact of allelic status, VAF, and complex karyotype (CK). In our cohort, the significance of biallelic status was limited to MDS with <5% blasts and not for blasts 5% to 9%, as proposed by the International Consensus Classification (ICC), or 5% to 19%, as proposed by the fifth edition of the WHO (WHO-5). MDS-EB1 and -EB2 with VAF ≥10% had comparable survival (9.6 vs 7.2 months; P = .12), regardless of allelic status. Contrary to the ICC proposal, MDS-EB1/EB2 with VAF <10% and CK had poor survival compared with those without CK, comparable to MDS-EB1/EB2 with VAF ≥10% (5.6 vs 26.2 vs 6.3 months; P = .003). Survival of TP53mut AML was poor (median 3.9 months) regardless of allelic/CK status. Thus, using ICC or WHO-5 may underestimate prognosis of MDS with blasts 5% to 19% and 5% to 9%, respectively. Collectively, the hierarchical model acknowledges poor survival of 91.9% TP53mut MDS and AML compared with 36.5% and 80.7% by WHO-5 and ICC, respectively.

Abstract INTRODUCTION Cognition is reduced at low and high glucose, reflecting cognitive vulnerability to glucose (CVG) fluctuations. The impact of glucose fluctuations on the aging brain remains unclear. We examined whether CVG is associated with plasma biomarkers of Alzheimer's disease (AD) pathology and neurodegeneration. METHODS Participants included N = 114 adults with type 1 diabetes assessed for processing speed and sustained attention using ecological momentary assessment (EMA) combined with continuous glucose monitoring (CGM). We characterized associations between CVG and amyloid beta (Aβ) 42/40, phosphorylated tau (p‐tau) 181 and 217, neurofilament light chain, and glial fibrillary acidic protein. RESULTS CVG was associated with all plasma biomarkers, except Aβ 42/40. CVG for sustained attention exhibited strong associations with p‐tau biomarkers that persisted across covariate specifications. DISCUSSION CVG may be a useful digital phenotype of AD. It remains unclear whether CVG contributes to versus arises from neurodegeneration. We consider possible mechanisms linking cognitive vulnerability and long‐term glucose variability to the development of neuropathology. Highlights Cognitive vulnerability to glucose (CVG) may be a useful digital phenotype of neurodegeneration. We used cognitive ecological momentary assessment and continuous glucose monitoring to investigate CVG's associations with plasma biomarkers. Associations of CVG for sustained attention and phosphorylated tau 181 remained significant across covariates. We discuss possible mechanisms relating glucose variability, cognition, and neurodegeneration.

Background: Artificial intelligence (AI) stroke imaging software is becoming mainstay in many hub-and-spoke hospitals. Brainomix 360 Stroke software is the market leader in Europe focused on leveraging simple imaging (non-contrast computerized topography (NCCT) and CT angiography (CTA)) and has recently been FDA-cleared for use in the USA. We evaluated the implementation of Brainomix 360 AI Stroke software in the 17 spoke, multi-state Mayo Clinic Health System (MCHS) telestroke network. Methods: This prospective study compared decision and treatment times before and after Brainomix AI implementation, as well as clinician feedback and simulated decision making to better understand any changes seen. Patients were included if they underwent telestroke evaluation at an MCHS emergency department within 90 days of implementation (2/9/2024-8/8/2024), and excluded if they were already admitted to the hospital or if video evaluation was not performed. Data collection included demographics, clinical decisions and treatment times. Qualitative surveys were conducted at baseline and evaluation end, as well as simulated decision making in 20 de-identified cases randomized to with/without AI through an online portal. Results: A total of 907 patients were included (444 pre- and 463 post-implementation, 287 (32%) with ischemic stroke final diagnosis). Median NIHSS was 2. IVT was recommended in 20.3% (27/148 ischemic stroke patients) pre- and 25.9% (36/139) post-implementation. EVT was recommended in 16.2% (24/148) pre and 14.4% (20/139) post. AI use was associated with trends of faster telestroke activation to IVT decision (36 vs 32 mins, p=0.6), IVT administration (47 vs 40 minutes, p=0.6), and EVT decision (36 vs 33 minutes, p=0.5). In the simulation, imaging interpretation was significantly faster when randomized to AI use (3.4 vs 2.1 mins, p<0.001) and associated with improved physician confidence (62 vs 88%, p=0.004). Qualitative feedback from 14/24 neurologists showed the greatest perceived value was improved confidence of treatment decisions (43%) and faster triaging (36%). Most value was gained from e-ASPECTS (NCCT) and LVO modules. Conclusion: This service evaluation highlighted the opportunity to improve efficiency of decision making even in the setting of a well-developed telestroke system. The impact was underpinned by the improved speed and confidence of imaging interpretation reflected in an offline simulation and qualitative feedback.

Abstract Background Intestinal colonization with carbapenem-resistant organisms (CRO) may be considered to inform empiric antibiotic selection for symptomatic infection. However, it is unclear how often gut colonizing CRE isolates are related to bloodstream isolates in hospitalized patients with bacteremia, especially in areas with high CRO prevalence. Minimum spanning tree of isolate relatedness Isolates and corresponding patient number (P1-P6) and rectal (R) or blood (B) specimen are noted within circles and allelic differences are numerated on linking lines between the circles. Group 1 and 3 isolates are possibly related to each other. Created with BioRender.com. Methods Patients with paired K. pneumoniae carbapenemase (KPC)-producing K. pneumoniae isolates cultured from surveillance rectal specimens and clinically collected blood specimens collected within 1-8 days of each other between 2019-2023 were identified at 3 Greek hospitals. Isolates were frozen and shipped to a reference laboratory in the U.S for whole genome sequencing (WGS) using Illumina MiSeq. Assembly and core genome multilocus sequence typing (cgMLST) analysis were performed with Ridom SeqSphere+ software. Isolate relatedness was based on the total number of allelic differences between each isolate: &lt; 15, related; 16-50, possibly related; ≥ 51, unrelated. Results One hundred eight paired isolates were identified from 54 unique patients; 6 pairs and 12 total isolates underwent cgMLST. In 5 of 6 pairs (83%), the rectal isolate was collected prior to the bloodstream isolate. Rectal and bloodstream isolates were related to one another in 5 of 6 (83%) pairs and were unrelated in 1 pair. Two pairs collected from 2 distinct patients admitted to the same intensive care unit (patients 2 and 3, Figure) were possibly related (16-50 allelic differences) to each other. Conclusion In this pilot evaluation conducted in a setting of high CRO prevalence, KPC-producing K. pneumoniae isolated from paired rectal and blood specimens from individual patients were often related to each other, suggesting that intestinal colonization by this organism could inform empiric antibiotic treatment for bacteremia. Two patients from the same hospital unit had isolates that were possibly related, suggesting within hospital transmission. WGS is a powerful tool that can inform clinical and infection control practices. WGS of the remaining K. pneumoniae pairs and additional Acinetobacter baumannii pairs is ongoing. Disclosures Robin Patel, MD, I already disclosed so please pull from disclosure for other abstracts: Advisor/Consultant|I already disclosed so please pull from disclosure for other abstracts: Grant/Research Support|I already disclosed so please pull from disclosure for other abstracts: Honoraria

AbstractBackgroundInflammatory bowel disease (IBD) affects more than 10 million people worldwide. Men and women are equally affected by Crohn's disease (CD). It has been shown that patients with CD are at an increased risk of a colorectal cancer (CRC) diagnosis and CRC‐related mortality. During the last two decades, biological therapies have revolutionized the treatment of CD. There are no current studies investigating the prevalence of CRC in patients with CD in the era of biological therapy and the possible features of patients with CD who are at high risk of developing CRC.AimWe aim to assess the prevalence of CRC, risk factors and profile of CRC in patients with CD receiving biological treatment compared with those who are not under biological therapy and the impact of CD‐associated colorectal strictures on CRC development. The study hypothesis is that the use of biological therapy in the control of CD activity may decrease the risk of developing CRC.Study design and settingAn international, retrospective, snapshot of the prevalence of CRC in patients with CD, reported according to the SPIRIT guidelines. The study will involve centres that hold regular IBD multidisciplinary team meetings and have both IBD colorectal surgeons and gastroenterologists. Each participating centre will provide a local consultant lead and a local trainee lead. Data will be collected within a 2‐year recruitment period (January 2017–January 2019).Study populationAdult patients who presented with CD during the study period. Patients with an incidental diagnosis of CD during evaluation for CRC will be excluded.Statistical planBaseline patient characteristics will be summarized using the appropriate descriptive statistics. Univariable, multivariable and Cox regression models will be used to identify factors significantly associated with CRC. For noncontinuous variables a comparison between the subgroups will be carried out using the chi‐square test corrected by Fisher's exact test if appropriate. A p‐value of <0.05 will be considered statistically significant.Data storageData will be stored on a secured server, pin‐code protected according to the local data management agreement.

SummaryThe age‐associated mutational state of clonal haematopoiesis (CH) is linked to multiple adverse health outcomes. As higher risk CH can lead to progressive neoplastic or vascular disease, there is interest in developing clinical trials to mitigate risk associated with CH. Given the high prevalence of CH, data from clinical trials could have broad public health implications for screening and therapy. Thoughtful consideration is needed to design trials that are both clinically relevant and avoid overmedicalization. Here, we summarize clinical studies of CH to date and provide suggestions and guidance on how to approach designing CH‐focused therapeutic clinical trials. These recommendations are derived from discussions among clinical researchers and scientists emanating from the Inaugural Meeting on Somatic Mutations and Predisease in October 2021.