Radiological Detection Research Articles

Assessment of ultrasound-guided tru-cut needle pleural biopsy in the diagnosis of unexplained exudative pleural effusion compared to medical thoracoscopy

Background Ultrasound-guided needle biopsy (USGNB) allows for precise and immediate viewing of pleural lesions, effusions, and needle placement without ionizing radiation. This study aimed to assess the efficacy of US-guided tru-cut needle pleural biopsy in diagnosing unexplained exudative pleural effusion compared to medical thoracoscopy (MT), focusing on safety, accuracy, time, and cost of the treatment. Patients and methods This observational cross-sectional research was conducted on 40 patients over 18 years old, of both sexes, with unexplained exudative pleural effusion. The patients were randomly separated into two equal groups. The girst group is USGNB and the second group is MT. Results Group II exhibited substantially greater costs, sedation levels, procedure duration, biopsy site discomfort, surgical emphysema, lung expansion failure, and psychological distress compared to group I (P<0.05). There was no notable disparity between the two groups regarding radiological detection of pleural effusion, pleural fluid properties, procedural observations, histological results, and diagnostic effectiveness. The duration of hospitalization was considerably shorter in group I compared to group II, assessed from the day of the operation to the day of release (P=0.001). Conclusion USGNB is an important tool in the diagnosis of pleural effusion after failure of pleural fluid analysis, which is performed by a chest physician is an accurate, safer, lower in cost, and shorter in duration with fewer complications compared with MT.

Longitudinal Analyses of Circulating Tumor DNA for the Detection of EGFR Mutation-Positive Advanced NSCLC Progression During Treatment: Data From FLAURA and AURA3

IntroductionEGFR tyrosine kinase inhibitor (EGFR-TKI)-sensitizing and -resistance mutations may be detected in plasma through circulating tumor DNA (ctDNA). Circulating tumor DNA level changes reflect alterations in tumor burden and could be a dynamic indicator of treatment effect. This analysis aimed to determine whether longitudinal EGFR-mutation ctDNA testing could detect progressive disease (PD) before radiologic detection. MethodsThis was a retrospective, exploratory ctDNA analysis in two phase 3 trials (FLAURA, NCT02296125; AURA3, NCT02151981). Patients had treatment-naïve (FLAURA) or EGFR-TKI pre-treated (AURA3) advanced NSCLC with EGFR mutations and on-study PD (RECIST [Response Evaluation Criteria in Solid Tumors]), with a baseline ctDNA result and EGFR-mutation ctDNA monitoring beyond Cycle 3 Day 1. Patients received osimertinib versus comparator EGFR-TKIs (FLAURA) or chemotherapy (AURA3). Outcomes included time from ctDNA PD to RECIST PD and the first subsequent treatment (FLAURA only). ResultsCirculating tumor DNA PD preceded or co-occurred with RECIST-defined PD in 93 out of 146 patients (64%) in FLAURA and 82 out of 146 patients (56%) in AURA3. Median time from ctDNA PD to RECIST-defined PD (mo) was 3.4 and 2.6 in the osimertinib and comparator EGFR-TKI arms (FLAURA) and 2.8 and 1.5 in the osimertinib and chemotherapy arms (AURA3). In FLAURA, the median time from ctDNA PD to the first subsequent treatment (mo) was 6.0 and 4.7 in the osimertinib (n = 51) and comparator EGFR-TKI arms (n = 70). ConclusionsAmong patients with EGFR mutation-positive advanced NSCLC receiving EGFR-TKI or chemotherapy with ctDNA data and RECIST-defined PD, ctDNA PD preceded/co-occurred with RECIST-defined PD in approximately 60% of cases. Longitudinal ctDNA monitoring may detect PD before radiologic PD.

Chemical, biological, radiological and nuclear event detection and classification using ontology interrogation and social media data

In an era where chemical, biological, radiological, and nuclear (CBRN) incidents present a grave threat to public safety, timely and accurate information is paramount. The complexity of the CBRN concept encompasses a range of incidents, each with unique and overlapping symptoms, related substances, and event descriptions. This study introduces an innovative approach to the development of a CBRN-specific ontology, uniting diverse data sources and domain expertise to construct a comprehensive repository of CBRN events, sub-events, their causes, symptoms, and toxic substances. Unlike prior methodologies reliant on keyword searches and predefined categories, our approach enables a holistic analysis of textual data by capturing intricate relationships between symptoms and toxic substances. We leverage this ontology in conjunction with a tailored interrogation algorithm to detect potential CBRN incidents through social media data. The algorithm was then tested on datasets of three actual CBRN incidents, one fictional incident (TV show) that simulated a nuclear incident and one non-CBRN. The interrogation algorithm was able to detect the five CBRN incidents accurately. However, the study showcased the need to extend the algorithm to distinguish between real and fictional CBRN incidents. These findings underscore the potential of this approach to deliver timely information on potential CBRN incidents. Nevertheless, the study acknowledged the inherent challenges and limitations in utilizing social media data, including the risk of misinformation, fictional events, fake news, and interference from malicious actors, all of which can affect the accuracy and reliability of the information collected.

Proximity extension assay in cerebrospinal fluid identifies neurofilament light chain as biomarker of neurodegeneration in sporadic cerebral amyloid angiopathy

BackgroundSporadic cerebral amyloid angiopathy (sCAA) is a disease characterised by the progressive deposition of the amyloid beta (Aβ) in the cerebral vasculature, capable of causing a variety of symptoms, from (mild) cognitive impairment, to micro- and major haemorrhagic lesions. Modern diagnosis of sCAA relies on radiological detection of late-stage hallmarks of disease, complicating early diagnosis and potential interventions in disease progression. Our goal in this study was to identify and validate novel biomarkers for sCAA.MethodsWe performed a proximity extension assay (PEA) on cerebrospinal fluid (CSF) samples of sCAA/control participants (n = 34/51). Additionally, we attempted to validate the top candidate biomarker in CSF and serum samples (n = 38/26) in a largely overlapping validation cohort, through analysis with a targeted immunoassay.ResultsThirteen proteins were differentially expressed through PEA, with top candidate NFL significantly increased in CSF of sCAA patients (p < 0.0001). Validation analyses using immunoassays revealed increased CSF and serum NFL levels in sCAA patients (both p < 0.0001) with good discrimination between sCAA and controls (AUC: 0.85; AUC: 0.79 respectively). Additionally, the CSF: serum NFL ratio was significantly elevated in sCAA (p = 0.002).DiscussionLarge-scale targeted proteomics screening of CSF of sCAA patients and controls identified thirteen biomarker candidates for sCAA. Orthogonal validation of NFL identified NFL in CSF and serum as biomarker, capable of differentiating between sCAA patients and controls.

Eligibility of a novel BW + technology and comparison of sensitivity and specificity of different imaging methods for radiological caries detection

ObjectivesBitewing radiography is considered to be of high diagnostic value in caries detection, but owing to projections, lesions may remain undetected. The novel bitewing plus (BW +) technology enables scrolling through radiographs in different directions and angles. The present study aimed at comparing BW + with other 2D and 3D imaging methods in terms of sensitivity, specificity, and user reliability.Materials and methodsFive human cadavers were used in this study. In three cadavers, natural teeth were transplanted post-mortem. BW + , two-dimensional (digital sensors, imaging plates, 2D and 3D bitewing radiographs) and 3D methods (high and low dose CBCT) were taken. Carious lesions were evaluated on 96 teeth at three positions (mesial, distal, and occlusal) and scored according to their level of demineralization by ten observers, resulting in 35,799 possible lesions across all observers and settings. For reference, µCT scans of all teeth were performed.ResultsOverall, radiographic evaluations showed a high rate of false-negative diagnoses, with around 70% of lesions remaining undetected, especially enamel lesions. BW + showed the highest sensitivity for dentinal caries and had comparatively high specificity overall.ConclusionsWithin the limits of the study, BW + showed great potential for added diagnostic value, especially for dentinal caries. However, the tradeoff of diagnostic benefit and radiation exposure must be considered according to each patient’s age and risk.

Enhancements in Radiological Detection of Metastatic Lymph Nodes Utilizing AI-Assisted Ultrasound Imaging Data and the Lymph Node Reporting and Data System Scale.

The paper presents a novel approach for the automatic detection of neoplastic lesions in lymph nodes (LNs). It leverages the latest advances in machine learning (ML) with the LN Reporting and Data System (LN-RADS) scale. By integrating diverse datasets and network structures, the research investigates the effectiveness of ML algorithms in improving diagnostic accuracy and automation potential. Both Multinominal Logistic Regression (MLR)-integrated and fully connected neuron layers are included in the analysis. The methods were trained using three variants of combinations of histopathological data and LN-RADS scale labels to assess their utility. The findings demonstrate that the LN-RADS scale improves prediction accuracy. MLR integration is shown to achieve higher accuracy, while the fully connected neuron approach excels in AUC performance. All of the above suggests a possibility for significant improvement in the early detection and prognosis of cancer using AI techniques. The study underlines the importance of further exploration into combined datasets and network architectures, which could potentially lead to even greater improvements in the diagnostic process.

Never tell me the odds: Investigating pro-hoc explanations in medical decision making

This paper examines a kind of explainable AI, centered around what we term pro-hoc explanations, that is a form of support that consists of offering alternative explanations (one for each possible outcome) instead of a specific post-hoc explanation following specific advice. Specifically, our support mechanism utilizes explanations by examples, featuring analogous cases for each category in a binary setting. Pro-hoc explanations are an instance of what we called frictional AI, a general class of decision support aimed at achieving a useful compromise between the increase of decision effectiveness and the mitigation of cognitive risks, such as over-reliance, automation bias and deskilling. To illustrate an instance of frictional AI, we conducted an empirical user study to investigate its impact on the task of radiological detection of vertebral fractures in x-rays. Our study engaged 16 orthopedists in a ‘human-first, second-opinion’ interaction protocol. In this protocol, clinicians first made initial assessments of the x-rays without AI assistance and then provided their final diagnosis after considering the pro-hoc explanations. Our findings indicate that physicians, particularly those with less experience, perceived pro-hoc XAI support as significantly beneficial, even though it did not notably enhance their diagnostic accuracy. However, their increased confidence in final diagnoses suggests a positive overall impact. Given the promisingly high effect size observed, our results advocate for further research into pro-hoc explanations specifically, and into the broader concept of frictional AI.

Circulating tumor cells reveal early predictors of disease progression in patients with stage III NSCLC undergoing chemoradiation and immunotherapy

Circulating tumor cells (CTCs) are early signs of metastasis and can be used to monitor disease progression well before radiological detection by imaging. Using an ultrasensitive graphene oxide microfluidic chip nanotechnology built with graphene oxide sheets, we were able to demonstrate that CTCs can be specifically isolated and molecularly characterized to predict future progression in patients with stage III non-small cell lungcancer (NSCLC). We analyzed CTCs from 26 patients at six time points throughout the treatment course of chemoradiation followed by immune checkpoint inhibitor immunotherapy. We observed that CTCs decreased significantly during treatment, where a larger decrease in CTCs predicted a significantly longer progression-free survival time. Durvalumab-treated patients who have future progression were observed to have sustained higher programmed death ligand 1+ CTCs compared to stable patients. Gene expression profiling revealed phenotypically aggressive CTCs during chemoradiation. By using emerging innovative bioengineering approaches, we successfully show that CTCs are potential biomarkers to monitor and predict patient outcomes in patients with stage III NSCLC.

Circulating tumor DNA (ctDNA) for informing adjuvant chemotherapy (ACT) in stage II/III colorectal cancer (CRC): Interim analysis of BESPOKE CRC study.

9 Background: ctDNA-based post-surgical detection of molecular residual disease (MRD) is known to be predictive of a high risk of recurrence. Here, we report the first results of BESPOKE CRC, a multicenter, prospective, observational study evaluating the ability of a tumor-informed ctDNA assay to inform ACT treatment decisions in stage II/III CRC patients (pts). Methods: Of the 1792 pts enrolled between 2020-07-02 and 2022-08-25, plasma samples from the first 350 pts with stage II-III CRC were analyzed. ctDNA was detected and quantified using a personalized, tumor-informed assay (Signatera, Natera, Inc.). Following curative resection, 232 pts received ACT and 118 underwent observation. Results: The cohort included 154 stage II and 196 stage III CRC pts; the median follow-up was 24.8 months. ctDNA results at the post-op MRD time point (tp) were available for 295 pts; 15.6% (46/295; stage II: 9/130=6.9%; stage III: 37/165=22.4%) of pts were ctDNA positive (ctDNA+) at MRD tp (MRD+). MRD-positivity was significantly associated with inferior disease-free survival (DFS) in stages II-III combined (HR=20.8, 95% CI: 10.0-43.4, p&lt;0.0001) and in stage-stratified subgroups (stage II: HR=25.7, 95% CI 6.8-96.7; stage III: HR=18.1, 95% CI 7.3-45.1). Within the MRD+ group, pts receiving ACT had longer DFS compared to those in the observation group (median DFS: 18.7 vs 6.7 months; HR=3.9, 95% CI: 1.3-11.5, p=0.01). In contrast, no benefit of ACT was observed in MRD- pts (HR=1.1, 95% CI: 0.3-3.9, p=0.89). Of the MRD+ pts, 39.1% (18/46) had ctDNA clearance at 12-weeks post-surgery tp. Pts with ctDNA clearance had longer DFS compared to those who remained positive (median DFS: 24.2 vs 13.8 months; HR=0.4, 95% CI 0.1-1.0, p=0.045), however, had worse DFS than pts who were ctDNA- at both 4- and 12-weeks (HR=22.5, 95% CI: 6.8-75.0, p&lt;0.0001). Notably, 44.4% (8/18) pts with ctDNA clearance recurred; all 8 turned back ctDNA+ before radiological detection of relapse. ctDNA results during surveillance were available for 339 pts, of whom 8.3% (58/339) were ctDNA+ and had significantly worse DFS compared to serially ctDNA- pts (HR=124.3, 95% CI: 29.8-518.7, p&lt;0.0001). Conclusions: ctDNA-based MRD detection of MRD was highly prognostic of recurrence in an early representative subset of BESPOKE CRC cohort. Data from the expanded cohort will be presented at the meeting. ctDNA MRD results were also predictive: significant benefit from ACT was observed in MRD+ but not in MRD- pts. Additionally, early ctDNA clearance in response to adjuvant therapy and ctDNA status during surveillance were prognostic of pt outcomes. Our results highlight the potential utility of ctDNA-guided adjuvant therapy in pts with stage II/III CRC. The results of BESPOKE CRC herein, as one of the first ctDNA-based prospective studies, will be further validated by ongoing ctDNA-directed randomized clinical trials. Clinical trial information: NCT04264702 .

Pure squamous cell carcinoma of primary pancreatic origin

Introduction. Primary, ?pure? squamous cell carcinoma (SCC) is an exceptionally rare pancreatic malignancy that has been described in sporadic case reports. The appearance of this rare entity created a diagnostic dilemma for us, therefore, in this case report, we are focused on the radiological detection and characterization, pathogenesis, and therapeutic options of pure pancreatic SCC. Case outline. In an 80-year-old female patient, a partially necrotic mass in the tail of the pancreas was detected by computed tomography, which is the rarest localization of this tumor. On the performed imaging, the tumor showed predominantly malignant features with a surprising definitive histopathological diagnosis in the direction of pure SCC. Distal pancreatectomy with splenectomy was performed because of the infiltration of lienal vascular structures. Conclusion. Due to the very aggressive form of this tumor and poor prognosis, early detection, risk factors control, genetic burden, and optimization of surgical and therapeutic management can improve the quality of life and prolong the overall survival period.

Front-line liquid biopsy for early molecular assessment and treatment of hospitalized lung cancer patients

BackgroundMolecular characterization is pivotal for managing non-small cell lung cancer (NSCLC), although this process is often time-consuming and patients’ conditions might worsen while molecular analyses are processed.Our primary aim was to evaluate the performance of “up-front” next-generation sequencing (NGS) through liquid biopsy (LB) of hospitalized patients with newly detected lung neoplasm in parallel with conventional diagnosis. The secondary aim included longitudinal monitoring through LB of patients with oncogenic alterations at baseline. MethodsWe enrolled 47 consecutive patients immediately after hospitalization and radiological detection of symptomatic lung neoplasm. LB from peripheral blood was performed at baseline, in parallel with conventional biopsy (CB), when feasible. Additionally, LBs were repeated during treatment in patients with actionable gene alterations at baseline. Oncomine™ Lung cfTNA Research Assay panel was employed for processing plasma samples in NGS. Results47 hospitalized patients were enrolled. LB identified 28 patients with gene alterations, including mutations of EGFR (n = 7), KRAS (n = 12), ERBB2 (n = 1), TP53 (n = 2), BRAF (n = 1), one ALK rearrangement, and 4 patients with combined mutations involving EGFR, KRAS and PIK3CA.LB and CB were consistent, except for two patients. Three patients with positive LB for oncogenic drivers did not undergo CB due to contraindications.Median time to molecular results after LB was significantly lower compared to time to molecular report after CB (11 versus 22 days, p < 0.001). ConclusionsDespite limited numbers, our study supports the role of front-line LB for improving management of symptomatic patients with lung cancer, potentially leading to early targeted therapy initiation.

Children with Rare Nager Syndrome-Literature Review, Clinical and Physiotherapeutic Management.

Nager syndrome is a rare human developmental disorder characterized by craniofacial defects including the downward slanting of the palpebral fissures, cleft palate, limb deformities, mandibular hypoplasia, hypoplasia or absence of thumbs, microretrognathia, and ankylosis of the temporomandibular joint. The prevalence is very rare and the literature describes only about a hundred cases of Nager syndrome. There is evidence of autosomal dominant and autosomal recessive inheritance for Nager syndrome, suggesting genetic heterogeneity. The majority of the described causes of Nager syndrome include pathogenic variants in the SF3B4 gene, which encodes a component of the spliceosome; therefore, the syndrome belongs to the spliceosomopathy group of diseases. The diagnosis is made on the basis of physical and radiological examination and detection of mutations in the SF3B4 gene. Due to the diversity of defects associated with Nager syndrome, patients require multidisciplinary, complex, and long-lasting treatment. Usually, it starts from birth until the age of twenty years. The surgical procedures vary over a patient's lifetime and are related to the needed function. First, breathing and feeding must be facilitated; then, oral and facial clefts should be addressed, followed by correcting eyelid deformities and cheekbone reconstruction. In later age, a surgery of the nose and external ear is performed. Speech and hearing disorders require specialized logopedic treatment. A defect of the thumb is treated by transplanting a tendon and muscle or transferring the position of the index finger. In addition to surgery, in order to maximize a patient's benefit and to reduce functional insufficiency, complementary treatments such as rehabilitation and physiotherapy are recommended. In our study, we describe eight patients of different ages with various cases of Nager syndrome. The aim of our work was to present the actual genetic knowledge on this disease and its treatment procedures.

Clinical profile, referral trends, and real-world application of vibration-controlled transient elastography in children with non-alcoholic fatty liver disease in Singapore.

Pediatric non-alcoholic fatty liver disease (NAFLD) is a progressive disorder that is increasing in incidence globally. The study aims to describe the clinical profile and longitudinal outcome, including the utility of vibration-controlled transient elastography (VCTE), in children with NAFLD at a single tertiary liver unit in Singapore. Retrospective review of patients aged 0-18 years referred for NAFLD from 2003 to 2020 was conducted. Diagnosis was based on persistent elevation of alanine transaminase ≥2× the upper limit of normal in at-risk patients, and/or radiologic detection of hepatic steatosis, with the exclusion of other etiologies. VCTE-derived liver stiffness measurements (LSMs) ≤7.0 , 7.1-9.0, and ≥9.1 kPa were used to differentiate normal (F0-F1), significant fibrosis (F2), and advanced fibrosis (F3-F4), respectively. The study included 210 patients (72.4% male, mean age 11.6 years). New cases increased from 1.7/1000 referrals in 2003-2008 to 12.7 and 24.5/1000 referrals in 2009-2014 and 2015-2020, respectively. Significant proportion had dyslipidemia (41.4%), impaired glucose tolerance/diabetes (IGT/DM, 26.7%), and hypertension (17.1%). Only 6.2% had resolution of NAFLD after a mean follow-up of 3.7 years. Based on VCTE (n = 65), 41.5% had normal LSM, while 26.2% and 32.3% had increased likelihood of significant and advanced fibrosis, respectively. Age ≥16 years (odds ratio [OR] 8.9), IGT/DM (OR 6.5), and aspartate transaminase >70 U/L (OR 11.0) were independent risk factors associated with increased likelihood of advanced fibrosis. Incidence of pediatric NAFLD has increased dramatically in Singapore. Based on LSM estimation, pediatric NAFLD may be associated with an increased risk of developing advanced fibrosis by late adolescence.

Concomitant Immunotherapy and Metastasis-Directed Radiotherapy in Upper Tract Urothelial Carcinoma: A Biomarker-Driven, Original, Case-Based Proof-of-Concept Study.

Metastatic upper tract urothelial carcinoma (mUTUC) has a poor prognosis. Immune checkpoint inhibitors (ICIs) have demonstrated efficacy in patients with metastatic urothelial carcinoma. However, data supporting the use of ICIs in patients with mUTUC are limited. A promising synergy between ICI and concomitant radiotherapy (RT) has been reported in patients with mUTUC. Our research involved a case-based investigation and emphasized the successful integration of different specialists' skills. Observed after partial urethrectomy procedures for muscle-invasive upper tract urothelial carcinoma (UTUC), the radiological detection of lung metastases prompted us to implement cisplatin-based first-line chemotherapy and molecular characterization in the treatment process. We uncovered alterations in the ERBB2 and FGFR3 genes and mismatch repair deficiency at a molecular level. First-line chemotherapy treatment led to a stable disease, and the patient was started on maintenance immunotherapy with Avelumab. Subsequently, an increase in the size of the lung nodules was described, and the patient received radiotherapy for three lung lesions in combination with immunotherapy. After 3 months, a restaging CT scan reported a complete response, which is still ongoing. We discuss the mechanisms driving RT/ICI synergy and the molecular profile of mUTUC as factors that should be considered in therapeutic strategy planning. Molecular insight enhances the originality of our study, providing a nuanced understanding of the genetic landscape of mUTUC and paving the way for targeted therapeutic strategies. The therapeutic armamentarium expansion encourages the design of a multimodal and personalized approach for each mUTUC patient, taking into account tumor heterogeneity and molecular profiling.

Refining MRI-based criteria for portal vein invasion in hepatocellular carcinoma: improving sensitivity beyond portal vein tumor thrombosis.

To investigate the imaging features indicating portal vein invasion (PVI) of hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced MRI and to create more accurate diagnostic criteria than the presence of portal vein tumor thrombosis (PVTT) on MRI. This retrospective study included patients with surgically resected HCC larger than 5 cm, and the presence of PVI was investigated. On MRI, we evaluated the image findings of portal vein occlusion, the parenchymal signal change caused by hemodynamic alterations of the portal vein, and their combination showing the highest odds ratio (OR) to define the diagnostic criteria for radiological PVI detection (rPVI criteria). The diagnostic performance and recurrence-free survival were compared between the rPVI criteria and the presence of PVTT using McNemar's test and Kaplan-Meier method, respectively. Interobserver agreement was evaluated using Cohen's weighted ĸ statistics. Of 189 enrolled patients, 25 (13.2%) had PVI on histology. To diagnose PVI on MRI, either peripheral wedge-shaped arterial peritumoral hyperemia with an abrupt cut-off of a portal vein or the presence of PVTT had the highest OR (41.67, p<0.001). The sensitivity of PVI was significantly increased under this diagnostic criterion (64.0% to 88.0%; p=0.031) with comparable accuracy (95.2% vs. 94.7%; p>0.999). In terms of recurrence-free survival, the patient group with rPVI was significantly worse (p=0.017) compared with the patients without rPVI. Interobserver agreement of radiologic findings was substantial (ĸ=0.64). Diagnostic criteria for radiologically PVI detection increase the sensitivity more than the only presence of PVTT.

EXTH-36. COMBINING ONC201 AND PAXALISIB FOR THE TREATMENT OF DIFFUSE MIDLINE GLIOMA (DMG); THE PRECLINICAL RESULTS UNDERPINNING THE INTERNATIONAL PHASE II CLINICAL TRIAL (NCT05009992)

Abstract Diffuse midline gliomas (DMGs) diagnosed in the pons (DIPG) are universally fatal central nervous system tumors and are the leading cause of cancer-related death in children. Palliative radiotherapy is the only recognized treatment, with median overall survival just 9-11 months. The brain-penetrant, small molecule, ONC201, shows early-stage clinical trial efficacy, extending survival by ~9-11 months compared to historic controls. However, studies to determine the mechanisms behind the temporary clinical response to ONC201 are needed. Here, we have used a systems-biological approach to investigate whether genomic features influenced ONC201 response. DMGs harboring PIK3CA mutations were more sensitive to ONC201, whereas those harboring TP53 mutations were less sensitive. Quantitative proteogenomics identified that ONC201 elicits potent agonism of the mitochondrial protease, ClpP, driving proteolysis of electron transport chain and tricarboxylic acid proteins, leading to mitochondrial dysfunction. However, metabolic adaptation to ONC201 is promoted by the spare redox-signaling capacity of cells harboring WT-PIK3CA that was counteracted using the brain-penetrant PI3K/Akt/mTOR inhibitor, paxalisib. ONC201 and paxalisib combinations extended survival of orthotopic DIPG xenograft mouse models (SU-DIPG-VI, p=0.0027; SF8626, p=0.0002; HSJD-DIPG-007, p=&amp;lt; 0.0001). The combination in the first three recorded patients; two at progression following re-irradiation, and one at diagnosis following the completion of radiation, resulted in dramatic reductions in tumor area, dramatically extending overall survival for all three patients (25 months, 30 and 31 months continuing). The DIPG patient receiving the combination since diagnosis, remains in progression free survival (MR axial diagnosis scan = 1554 mm2, current tumour area = 306 mm2, ~80% reduction). The patient continuing to receive the combination at progression and following reirradiation also experienced a marked decrease in tumor size (MR axial diagnosis scan = 1248 mm2, current tumour area = 315 mm2, ~75% reduction), 10 months following radiological detection of progression. These data inform the phase II clinical trial (NCT05009992).

Incidental radiological detection of pancreatic malformation: A diagnosis to take into account

Incidental radiological detection of pancreatic malformation: A diagnosis to take into account

Radiological Detection of Cardiac Amyloid: MRI with Pathological Correlation

Radiological Detection of Cardiac Amyloid: MRI with Pathological Correlation

Use of osilodrostat alongside 11C-Methionine PET CT in pituitary-dependent Cushing's disease may improve radiological detection and lead to better outcomes

Use of osilodrostat alongside 11C-Methionine PET CT in pituitary-dependent Cushing's disease may improve radiological detection and lead to better outcomes

Synthetic Control of Thorium Metal‐Organic Frameworks for Sequencing and Sensing of Radioiodine Species

Comprehensive SummaryExploring the physiochemical properties and expanding the applications of actinide‐containing materials is paramount to address the escalating challenge of radioactive waste accumulation. However, unlocking the full potential of these materials is largely crippled by the radiotoxicity of the actinides. We report here two porous and luminescent thorium‐based metal‐organic frameworks (Th‐BITD‐1 and Th‐BITD‐2) that serve as a bifunctional platform for sequencing and sensing of radioiodine, a much more radioactive fission product discharged during the nuclear fuel reprocessing. In particular, Th‐BITD‐1 displays better iodine uptake performance than Th‐BITD‐2 via the solution‐based process and vapor diffusion with the maximum adsorption capacities of 831 and 1099 mg/g, respectively. Furthermore, Th‐BITD‐1 can function as a highly sensitive luminescence sensor for iodate with a quenching constant (KSV) of 6.6(5) × 103 M−1 and a detection limit of 2.02 μM, respectively, outperforming 2.96(6) × 103 M−1 and 10.5 μM of Th‐BITD‐2. Moreover, a positive correlation between the sensing efficacy and the iodate adsorption capacity has been revealed. This work highlights the opportunity in designing novel actinide‐based MOFs for their potential applications in radiological fields, e.g., radionuclide separation and detection.