: Motion-impaired CT images can result in limited or suboptimal diagnostic interpretation (with missed or miscalled lesions) and patient recall. We trained and tested an artificial intelligence (AI) ...model for identifying substantial motion artifacts on CT pulmonary angiography (CTPA) that have a negative impact on diagnostic interpretation.
: With IRB approval and HIPAA compliance, we queried our multicenter radiology report database (mPower, Nuance) for CTPA reports between July 2015 and March 2022 for the following terms: "motion artifacts", "respiratory motion", "technically inadequate", and "suboptimal" or "limited exam". All CTPA reports were from two quaternary (Site A,
= 335; B,
= 259) and a community (C,
= 199) healthcare sites. A thoracic radiologist reviewed CT images of all positive hits for motion artifacts (present or absent) and their severity (no diagnostic effect or major diagnostic impairment). Coronal multiplanar images from 793 CTPA exams were de-identified and exported offline into an AI model building prototype (Cognex Vision Pro, Cognex Corporation) to train an AI model to perform two-class classification ("motion" or "no motion") with data from the three sites (70% training dataset,
= 554; 30% validation dataset,
= 239). Separately, data from Site A and Site C were used for training and validating; testing was performed on the Site B CTPA exams. A five-fold repeated cross-validation was performed to evaluate the model performance with accuracy and receiver operating characteristics analysis (ROC).
: Among the CTPA images from 793 patients (mean age 63 ± 17 years; 391 males, 402 females), 372 had no motion artifacts, and 421 had substantial motion artifacts. The statistics for the average performance of the AI model after five-fold repeated cross-validation for the two-class classification included 94% sensitivity, 91% specificity, 93% accuracy, and 0.93 area under the ROC curve (AUC: 95% CI 0.89-0.97).
: The AI model used in this study can successfully identify CTPA exams with diagnostic interpretation limiting motion artifacts in multicenter training and test datasets.
: The AI model used in the study can help alert technologists about the presence of substantial motion artifacts on CTPA, where a repeat image acquisition can help salvage diagnostic information.
We have studied the structural changes induced by optical excitation of the chromophore in wild-type photoactive yellow protein (PYP) in liquid solution with a combined approach of ...polarization-sensitive ultrafast infrared spectroscopy and density functional theory calculations. We identify the nuC8-C9 marker modes for solution phase PYP in the P and I0 states, from which we derive that the first intermediate state I0 that appears with a 3 ps time constant can be characterized to have a cis geometry. This is the first unequivocal demonstration that the formation of I0 correlates with the conversion from the trans to the cis state. For the P and I0 states we compare the experimentally measured vibrational band patterns and anisotropies with calculations and find that for both trans and cis configurations the planarity of the chromophore has a strong influence. The C7=C8-(C9=O)-S moiety of the chromophore in the dark P state has a trans geometry with the C=O group slightly tilted out-of-plane, in accordance with the earlier reported structure obtained in an X-ray diffraction study of PYP crystals. In the case of I0, experiment and theory are only in agreement when the C7=C8-(C9=O)-S moiety has a planar configuration. We find that the carboxylic side group of Glu46 that is hydrogen-bonded to the chromophore phenolate oxygen does not alter its orientation on going from the electronic ground P state, via the electronic excited P state to the intermediate I0 state, providing conclusive experimental evidence that the primary stages of PYP photoisomerization involve flipping of the enone thioester linkage without significant relocation of the phenolate moiety.
Despite rising popularity and performance, studies evaluating the use of large language models for clinical decision support are lacking. Here, we evaluate ChatGPT (Generative Pre-trained ...Transformer)-3.5 and GPT-4's (OpenAI, San Francisco, California) capacity for clinical decision support in radiology via the identification of appropriate imaging services for two important clinical presentations: breast cancer screening and breast pain.
We compared ChatGPT's responses to the ACR Appropriateness Criteria for breast pain and breast cancer screening. Our prompt formats included an open-ended (OE) and a select all that apply (SATA) format. Scoring criteria evaluated whether proposed imaging modalities were in accordance with ACR guidelines. Three replicate entries were conducted for each prompt, and the average of these was used to determine final scores.
Both ChatGPT-3.5 and ChatGPT-4 achieved an average OE score of 1.830 (out of 2) for breast cancer screening prompts. ChatGPT-3.5 achieved a SATA average percentage correct of 88.9%, compared with ChatGPT-4's average percentage correct of 98.4% for breast cancer screening prompts. For breast pain, ChatGPT-3.5 achieved an average OE score of 1.125 (out of 2) and a SATA average percentage correct of 58.3%, as compared with an average OE score of 1.666 (out of 2) and a SATA average percentage correct of 77.7%.
Our results demonstrate the eventual feasibility of using large language models like ChatGPT for radiologic decision making, with the potential to improve clinical workflow and responsible use of radiology services. More use cases and greater accuracy are necessary to evaluate and implement such tools.
Abstract Hyponatremia is a common finding in adults hospitalized with heart failure (HF) and is associated with longer hospital stays and increased mortality. The significance of hyponatremia in ...children with HF is not known. We sought to determine the incidence of hyponatremia and association with clinical outcome in children hospitalized with heart failure. Admission and inpatient serum sodium concentrations were analyzed in 141 consecutive children hospitalized with acute decompensated HF. Inclusion criteria: patients age birth to 21 years with biventricular hearts who were hospitalized for HF from 1/2007 to 12/2012. The primary composite end-point was death, cardiac transplantation or use of mechanical circulatory support (MCS) during hospitalization. Data for 141 patients were included in the analysis. The cohort included 48 (34%) patients with pre-existing HF. Mean serum sodium at admission was 136 ±4 mmol/L (range 124 to 150 mmol/L). Hyponatremia (serum sodium <135 mmol/L) was present in 45 (32%) patients at admission. Seventy-one patients (75%) with normal serum sodium concentrations at admission subsequently developed acquired hyponatremia during their hospitalization. Hyponatremia persisted at discharge in 17/66 (26%) of patients. Fifty-eight (41%) patients reached the composite end-point during hospitalization (death, n=15; cardiac transplantation, n=27; MCS, n=46). Hyponatremia at admission was independently associated with death, cardiac transplantation or the use of MCS during hospitalization (OR 3.1, p=0.02). In conclusion, hyponatremia occurs commonly in children hospitalized with acute decompensated HF and is associated with increased risk of in-hospital mortality, cardiac transplantation and need for MCS.
Objectives Controversy exists regarding the importance of circulating antibodies as determined by panel-reactive antibody screening as a risk factor for graft failure in pediatric patients undergoing ...heart transplantation. This study sought to determine the association of elevated anti-human leukocyte antibodies with long-term survival in pediatric heart transplant patients. Methods The United Network for Organ Sharing registry was queried for pediatric patients (aged < 18 years at listing) with panel-reactive antibody levels obtained before heart transplantation from 1987 through 2004. Survival analysis methods were used to assess the association of elevated panel-reactive antibodies with long-term graft and patient survival. Results Panel-reactive antibodies were obtained before transplantation from 3534 patients, median age 4 years (interquartile range 0–12 years). Most, 2711 (77%), had no detectible panel-reactive antibodies, 436 (12%) had panel-reactive antibodies of 1% to 10%, and 387 (11%) had panel-reactive antibodies greater than 10%. Patients with panel-reactive antibodies greater than 10% were more likely to be older ( P = .04), have congenital heart disease ( P < .001), and have a longer wait list time ( P = .006). Patients with panel-reactive antibodies greater than 10% had significantly worse graft survival and patient survival than did patients with undetectable panel-reactive antibodies and panel-reactive antibodies of 1% to 10% ( P < .05 for all). Controlling for confounding variables, elevated panel-reactive antibodies as a continuous variable and panel-reactive antibodies greater than 10% as a categorical variable were independently associated with decreased graft survival ( P = .04 and P = .02, respectively). Conclusions Elevated panel-reactive antibodies are independently associated with worse long-term graft survival in pediatric patients undergoing heart transplantation. Further study is needed to determine the optimal management of this high-risk population.
The chondrocytes' pericellular matrix acts as a mechanosensor by sequestering growth factors that are bound to heparan sulfate (HS) proteoglycans. Heparanase is the sole mammalian enzyme with HS ...degrading endoglycosidase activity. Here, we aimed to ascertain whether heparanase plays a role in modulating the anabolic or catabolic responses of human articular chondrocytes.
Primary chondrocytes were incubated with pro-heparanase and catabolic and anabolic gene expression was analyzed by quantitative polymerase chain reaction (PCR). MMP13 enzymatic activity in the culture medium was measured with a specific fluorescent assay. Extracellular regulated kinase (ERK) phosphorylation was evaluated by Western blot. Human osteoarthritis (OA) cartilage was assessed for heparanase expression by reverse-transcriptase PCR, by Western blot and by a heparanase enzymatic activity assay.
Cultured chondrocytes rapidly associated with and activated pro-heparanase. Heparanase induced the catabolic genes MMP13 and ADAMTS4 and the secretion of active MMP13, and down-regulated the anabolic genes ACAN and COL2A1. PG545, a HS-mimetic, inhibited the effects of heparanase. Heparanase expression and enzymatic activity were demonstrated in adult human osteoarthritic cartilage. Heparanase induced ERK phosphorylation in cultured chondrocytes and this could be inhibited by PG545, by fibroblast growth factor 2 (FGF2) neutralizing antibodies and by a FGF-receptor inhibitor.
Heparanase is active in osteoarthritic cartilage and induces catabolic responses in primary human chondrocytes. This response is due, at least in part, to the release of soluble growth factors such as FGF2.
Radiologic tests often contain rich imaging data not relevant to the clinical indication. Opportunistic screening refers to the practice of systematically leveraging these incidental imaging ...findings. Although opportunistic screening can apply to imaging modalities such as conventional radiography, US, and MRI, most attention to date has focused on body CT by using artificial intelligence (AI)-assisted methods. Body CT represents an ideal high-volume modality whereby a quantitative assessment of tissue composition (eg, bone, muscle, fat, and vascular calcium) can provide valuable risk stratification and help detect unsuspected presymptomatic disease. The emergence of "explainable" AI algorithms that fully automate these measurements could eventually lead to their routine clinical use. Potential barriers to widespread implementation of opportunistic CT screening include the need for buy-in from radiologists, referring providers, and patients. Standardization of acquiring and reporting measures is needed, in addition to expanded normative data according to age, sex, and race and ethnicity. Regulatory and reimbursement hurdles are not insurmountable but pose substantial challenges to commercialization and clinical use. Through demonstration of improved population health outcomes and cost-effectiveness, these opportunistic CT-based measures should be attractive to both payers and health care systems as value-based reimbursement models mature. If highly successful, opportunistic screening could eventually justify a practice of standalone "intended" CT screening.
Aims
Cardiovascular (CV) disease is a major cause of reduced life expectancy in type 1 diabetes (T1D). Intensive insulin therapy prevents CV complications but is constrained by hypoglycaemia and ...weight gain. Adjunct metformin reduces insulin dose requirement and stabilizes weight but there are no data on its cardiovascular effects. We have therefore initiated an international double‐blind, randomized, placebo‐controlled trial (REMOVAL: REducing with MetfOrmin Vascular Adverse Lesions in type 1 diabetes) to examine whether metformin reduces progression of atherosclerosis in adults with T1D. Individuals ≥40 years of age with T1D for ≥5 years are eligible if they have ≥3 of 10 specified CV risk factors. The enrolment target is 500 participants in 17 international centres.
Materials and methods
After 12 weeks of single‐blind placebo‐controlled run‐in, participants with ≥ 70% adherence are randomized to metformin or matching placebo for 3 years with insulin titrated towards HbA1c 7.0% (53 mmol/mol). The primary endpoint is progression of averaged mean far wall common carotid intima‐media thickness (cIMT) measured by ultrasonography at baseline, 12, 24 and 36 months. This design provides 90% power to detect a mean difference of 0.0167 mm in cIMT progression between treatment arms (α = 0.05), assuming that up to 20% withdraw or discontinue treatment. Other endpoints include HbA1c, weight, LDL cholesterol, insulin requirement, progression of retinopathy, endothelial function and frequency of hypoglycaemia.
Conclusion
REMOVAL is the largest clinical trial of adjunct metformin therapy in T1D to date and will provide clinically meaningful information on its potential to impact CV disease and other complications.
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