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Pancreatic ductal adenocarcinoma (PDAC) remains a difficult disease to treat and continues to portend a poor prognosis, as most patients are unresectable at diagnosis. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) combined with CT (PET/CT) has been a cornerstone in oncological imaging of different cancers; however, the role of PET/CT in PDAC is continually evolving and currently not well established. Studies have shown the potential of PET/CT in guiding the management of patients with PDAC, with possible added benefit over anatomic imaging with CT or MRI in certain scenarios. PET/CT may be useful in diagnosis, initial staging, treatment response assessment, differentiation of recurrent tumor from post-treatment fibrosis, and radiotherapy planning. Additionally, PET/CT may be a cost-effective modality due to upstaging of patients originally deemed as surgical candidates. Recently, the advent of simultaneous PET/MRI represents an exciting advancement in hybrid functional imaging with potential applications in the imaging of PDAC. The advantages of PET/MRI include simultaneous acquisition to improve registration of fusion images, lower radiation dose, superior soft tissue contrast, and availability of multiparametric imaging. Studies are underway to evaluate the utility of PET/MRI in PDAC, including in initial staging and treatment response assessment and to determine the subgroup of patients that will benefit from PET/MRI. Further studies are warranted in both PET/CR and PET/MRI to better understand the role of these modalities in PDAC.

ObjectiveThe diagnosis of autoimmune pancreatitis (AIP) is challenging. Sonographic and cross-sectional imaging findings of AIP closely mimic pancreatic ductal adenocarcinoma (PDAC) and techniques for tissue sampling of AIP are suboptimal. These limitations often result in delayed or failed diagnosis, which negatively impact patient management and outcomes. This study aimed to create an endoscopic ultrasound (EUS)-based convolutional neural network (CNN) model trained to differentiate AIP from PDAC, chronic pancreatitis (CP) and normal pancreas (NP), with sufficient performance to analyse EUS video in real time.DesignA database of still image and video data obtained from EUS examinations of cases of AIP, PDAC, CP and NP was used to develop a CNN. Occlusion heatmap analysis was used to identify sonographic features the CNN valued when differentiating AIP from PDAC.ResultsFrom 583 patients (146 AIP, 292 PDAC, 72 CP and 73 NP), a total of 1 174 461 unique EUS images were extracted. For video data, the CNN processed 955 EUS frames per second and was: 99% sensitive, 98% specific for distinguishing AIP from NP; 94% sensitive, 71% specific for distinguishing AIP from CP; 90% sensitive, 93% specific for distinguishing AIP from PDAC; and 90% sensitive, 85% specific for distinguishing AIP from all studied conditions (ie, PDAC, CP and NP).ConclusionThe developed EUS-CNN model accurately differentiated AIP from PDAC and benign pancreatic conditions, thereby offering the capability of earlier and more accurate diagnosis. Use of this model offers the potential for more timely and appropriate patient care and improved outcome.

The ratio kcat / KM – often referred to as the ‘specificity constant’ – is a useful index for comparing the relative rates of an enzyme acting on alternative, competing substrates. However, an alternative description, ‘catalytic efficiency’, is frequently used, and on occasions misused, to compare the reactivity of two enzymes acting on the same substrate. Here, we highlight the pitfalls in using kcat / KM to compare the catalytic effectiveness of enzymes.

Purpose To describe the imaging appearance of hyperenhancing nodules arising in post-Fontan patients and to identify specific features best correlated with malignancy. Methods Hyperenhancing hepatic nodules visible on CT and/or MRI in post-Fontan patients were identified retrospectively and reviewed by subspecialty radiologists. Nodules with characteristic imaging findings of focal nodular hyperplasia (FNH) were defined as typical, the remainder were defined as atypical, described in detail according to LIRADS criteria, and length of stability over time was recorded. Clinical data, alpha fetoprotein levels (AFP), central venous pressures (CVP), and histopathology were recorded. Results 245 hyperenhancing nodules (215 typical, 30 atypical) were evaluated in 30 patients. Twenty-nine atypical nodules showed washout (portal phase in 6, delayed phase in 29), 0 showed pseudocapsule, 1 showed threshold growth, 1 showed tumor in vein, and 5 showed ancillary features favoring malignancy. Pathology confirmed hepatocellular carcinoma (HCC) in 3 atypical nodules and FNH-like histology in 3 atypical and 4 typical nodules. 2 atypical nodules were present in a patient with clinical diagnosis of HCC. 20 nodules (7 typical, 13 atypical due to washout) were studied with hepatobiliary contrast agent and all showed homogenous hepatobiliary phase retention. Atypical nodules were significantly more likely to be HCC than biopsy-proven FNH-like or stable ≥24 months when showing portal phase washout ( P  < 0.001), mosaic architecture ( P  = 0.020) or in the presence of cirrhosis ( P  = 0.004) or elevated AFP ( P  = 0.004). Atypical nodules that were HCC had higher median CVP than those that were FNH-like (19, range 16–27 vs. 13, range 12–16 mmHg, P  = 0.0003), there was not a significant difference based on median patient age (HCC 30, range 10–41 vs. FNH-like 40 range 10–41, P  = 0.244). Conclusions Benign hyperenhancing masses in Fontan patients may demonstrate washout and be mistaken for HCC by imaging criteria. Portal phase washout, mosaic architecture, elevated AFP and higher CVP were associated with HCC in the atypical nodules found in this population.

There have been many publications detailing imaging features of malignant transformation of intraductal papillary mucinous neoplasms (IPMN), management and recommendations for imaging follow-up of diagnosed or presumed IPMN. However, there is no consensus on several practical aspects of imaging IPMN that could serve as a clinical guide for radiologists and enable future data mining for research. These aspects include how to measure IPMN, define reporting terminology, standardize reporting and unify guidelines for surveillance. The Society of Abdominal Radiology (SAR) created multiple Disease-Focused Panels (DFP) comprised multidisciplinary panel members who focus on a particular disease, with the goal to develop ways for radiologists to improve patient care, education, and research. DFP members met to identify the current controversies and limitations of imaging pancreatic IPMN. This paper aims to provide a practical review of the key imaging characteristics of IPMN for trainees and practicing radiologists, to guide uniformity of performance and interpretation of surveillance imaging studies, and to improve communication with clinicians by providing a lexicon and reporting template based on the experience of the SAR-DFP panel members.

TET/JBP (ten-eleven translocation/base J binding protein) enzymes are iron(II)- and 2-oxo-glutarate–dependent dioxygenases that are found in all kingdoms of life and oxidize 5-methylpyrimidines on the polynucleotide level. Despite their prevalence, few examples have been biochemically characterized. Among those studied are the metazoan TET enzymes that oxidize 5-methylcytosine in DNA to hydroxy, formyl, and carboxy forms and the euglenozoa JBP dioxygenases that oxidize thymine in the first step of base J biosynthesis. Both enzymes have roles in epigenetic regulation. It has been hypothesized that all TET/JBPs have their ancestral origins in bacteriophages, but only eukaryotic orthologs have been described. Here we demonstrate the 5mC-dioxygenase activity of several phage TETs encoded within viral metagenomes. The clustering of these TETs in a phylogenetic tree correlates with the sequence specificity of their genomically cooccurring cytosine C5-methyltransferases, which install the methyl groups upon which TETs operate. The phage TETs favor Gp5mC dinucleotides over the 5mCpG sites targeted by the eukaryotic TETs and are found within gene clusters specifying complex cytosine modifications that may be important for DNA packaging and evasion of host restriction.

Paliperidone palmitate is a long-acting injectable antipsychotic agent. This 13-week, multicenter, randomized (1 : 1 : 1 : 1), double-blind, parallel-group study evaluated the efficacy, safety, and tolerability of fixed 25, 50, and 100 milligram equivalent (mg equiv.) doses of paliperidone palmitate vs placebo administered as gluteal injections on days 1 and 8, then every 4 weeks (days 36 and 64) in 518 adult patients with schizophrenia. The intent-to-treat analysis set ( N =514) was 67% men and 67% White, with a mean age of 41 years. All paliperidone palmitate dose groups showed significant improvement vs placebo in the Positive and Negative Syndrome Scale (PANSS) total score (primary efficacy measure; 25 and 50 mg equiv., p =0.02; 100 mg equiv., p <0.001), as well as Clinical Global Impression Severity scores ( p ⩽0.006) and PANSS negative and positive symptom Marder factor scores ( p ⩽0.04). The Personal and Social Performance scale showed no significant difference between treatment groups. The overall incidence of treatment-emergent adverse events was similar between groups. Parkinsonism, the most frequently reported extrapyramidal symptom, was reported at similar rates for placebo (5%) and paliperidone palmitate (5–6% across doses). The mean body mass index and mean weight showed relatively small dose-related increases during paliperidone palmitate treatment. Investigator-evaluated injection-site pain, swelling, redness, and induration were similar across treatment groups; scores for patient-evaluated injection-site pain (visual analog scale) were similar across groups and diminished with time. All doses of once-monthly paliperidone palmitate were efficacious and generally tolerated, both locally and systemically. Paliperidone palmitate offers the potential to improve outcomes in adults with symptomatic schizophrenia.

Non-alcoholic fatty liver disease is the most common cause of chronic liver disease and affects nearly one-third of US population. With the increasing trend of obesity in the population, associated fatty change in the liver will be a common feature observed in imaging studies. Fatty liver causes changes in liver parenchyma appearance on imaging modalities including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI) and may affect the imaging characteristics of focal liver lesions (FLLs). The imaging characteristics of FLLs were classically described in a non-fatty liver. In addition, focal fatty change and focal fat sparing may also simulate FLLs. Knowledge of characteristic patterns of fatty change in the liver (diffuse, geographical, focal, subcapsular, and perivascular) and their impact on the detection and characterization of FLL is therefore important. In general, fatty change may improve detection of FLLs on MRI using fat suppression sequences, but may reduce sensitivity on a single-phase (portal venous) CT and conventional ultrasound. In patients with fatty liver, MRI is generally superior to ultrasound and CT for detection and characterization of FLL. In this pictorial essay, we describe the imaging patterns of fatty change in the liver and its effect on detection and characterization of FLLs on ultrasound, CT, MRI, and PET.

Background There is a critical need for effective treatment of the core symptoms of autism spectrum disorder (ASD). The purinergic antagonist suramin may improve core symptoms through restoration of normal mitochondrial function and reduction of neuro-inflammation via its known antagonism of P2X and P2Y receptors. Nonclinical studies in fragile X knockout mice and the maternal immune activation model support these hypotheses. Methods We conducted a 14 week, randomized, double-blind, placebo-controlled proof -of-concept study (N = 52) to test the efficacy and safety of suramin intravenous infusions in boys aged 4–15 years with moderate to severe ASD. The study had 3 treatment arms: 10 mg/kg suramin, 20 mg/kg suramin, and placebo given at baseline, week 4, and week 8. The Aberrant Behavior Checklist of Core Symptoms (ABC-Core) (subscales 2, 3, and 5) was the primary endpoint and the Clinical Global Impressions—Improvement (CGI-I) was a secondary endpoint. Results Forty-four subjects completed the study. The 10 mg/kg suramin group showed a greater, but statistically non-significant, numeric improvement (− 12.5 ± 3.18 [mean ± SE]) vs. placebo (− 8.9 ± 2.86) in ABC-Core at Week 14. The 20 mg/kg suramin group did not show improvement over placebo. In exploratory analyses, the 10 mg/kg arm showed greater ABC Core differences from placebo in younger subjects and among those with less severe symptoms. In CGI-I, the 10 mg/kg arm showed a statistically significant improvement from baseline (2.8 ± 0.30 [mean ± SE]) compared to placebo (1.7 ± 0.27) (p = 0.016). The 20 mg/kg arm had a 2.0 ± 0.28 improvement in CGI-I, which was not statistically significant compared to placebo (p = 0.65). Conclusion Suramin was generally safe and well tolerated over 14 weeks; most adverse events were mild to moderate in severity. Trial Registration Registered with the South African Health Authority, registration number DOH-27–0419-6116. ClinicalTrials.Gov registration ID is NCT06058962, last update posted 2023–09-28.

PurposeSingle-energy low tube potential (SE-LTP) and dual-energy virtual monoenergetic (DE-VM) CT images both increase the conspicuity of hepatic lesions by increasing iodine signal. Our purpose was to compare the conspicuity of proven liver lesions, artifacts, and radiologist preferences in dose-matched SE-LTP and DE-VM images.MethodsThirty-one patients with 72 proven liver lesions (21 benign, 51 malignant) underwent full-dose contrast-enhanced dual-energy CT (DECT). Half-dose images were obtained using single tube reconstruction of the dual-source SE-LTP projection data (80 or 100 kV), and by inserting noise into dual-energy projection data, with DE-VM images reconstructed from 40 to 70 keV. Three blinded gastrointestinal radiologists evaluated half-dose SE-LTP and DE-VM images, ranking and grading liver lesion conspicuity and diagnostic confidence (4-point scale) on a per-lesion basis. Image quality (noise, artifacts, sharpness) was evaluated, and overall image preference was ranked on per-patient basis. Lesion-to-liver contrast-to-noise ratio (CNR) was compared between techniques.ResultsMean lesion size was 1.5 ± 1.2 cm. Across the readers, the mean conspicuity ratings for 40, 45, and 50 keV half-dose DE-VM images were superior compared to other half-dose image sets (p < 0.0001). Per-lesion diagnostic confidence was similar between half-dose SE-LTP compared to half-dose DE-VM images (p ≥ 0.05; 1.19 vs. 1.24–1.32). However, SE-LTP images had less noise and artifacts and were sharper compared to DE-VM images less than 70 keV (p < 0.05). On a per-patient basis, radiologists preferred SE-LTP images the most and preferred 40–50 keV the least (p < 0.0001). Lesion CNR was also higher in SE-LTP images than DE-VM images (p < 0.01).ConclusionFor the same applied dose level, liver lesions were more conspicuous using DE-VM compared to SE-LTP; however, SE-LTP images were preferred more than any single DE-VM energy level, likely due to lower noise and artifacts.