Intermediate Likelihood Research Articles

Limbic Network Derangement Mediates Unawareness of Apathy in Mild Cognitive Impairment due to Alzheimer's Disease: Clues from [18F]FDG PET Voxel-Wise Analysis.

Discrepancy between caregiver and patient assessments of apathy in mild cognitive impairment (MCI) is considered an index of apathy unawareness, independently predicting progression to AD dementia. However, its neural underpinning are uninvestigated. To explore the [18F]FDG PET-based metabolic correlates of apathy unawareness measured through the discrepancy between caregiver and patient self-report, in patients diagnosed with MCI. We retrospectively studied 28 patients with an intermediate or high likelihood of MCI-AD, progressed to dementia over an average of two years, whose degree of apathy was evaluated by means of the Apathy Evaluation Scale (AES) for both patients (PT-AES) and caregivers (CG-AES). Voxel-based analysis at baseline was used to obtain distinct volumes of interest (VOIs) correlated with PT-AES, CG-AES, or their absolute difference (DISCR-AES). The resulting DISCR-AES VOI count densities were used as covariates in an inter-regional correlation analysis (IRCA) in MCI-AD patients and a group of matched healthy controls (HC). DISCR-AES negatively correlated with metabolism in bilateral parahippocampal gyrus, posterior cingulate cortex, and thalamus, PT-AES score with frontal and anterior cingulate areas, while there was no significant correlation between CG-AES and brain metabolism. IRCA revealed that MCI-AD patients exhibited reduced metabolic/functional correlations of the DISCR-AES VOI with the right cingulate gyrus and its anterior projections compared to HC. Apathy unawareness entails early disruption of the limbic circuitry rather than the classical frontal-subcortical pathways typically associated with apathy. This reaffirms apathy unawareness as an early and independent measure in MCI-AD, marked by distinct pathophysiological alterations.

Quality assurance of late gadolinium enhancement cardiac magnetic resonance images: a deep learning classifier for confidence in the presence or absence of abnormality with potential to prompt real-time image optimization

BackgroundLate gadolinium enhancement (LGE) of the myocardium has significant diagnostic and prognostic implications, with even small areas of enhancement being important. Distinguishing between definitely normal and definitely abnormal LGE images is usually straightforward, but diagnostic uncertainty arises when reporters are not sure whether the observed LGE is genuine or not. This uncertainty might be resolved by repetition (to remove artifact) or further acquisition of intersecting images, but this must take place before the scan finishes. Real-time quality assurance by humans is a complex task requiring training and experience, so being able to identify which images have an intermediate likelihood of LGE while the scan is ongoing, without the presence of an expert is of high value. This decision-support could prompt immediate image optimization or acquisition of supplementary images to confirm or refute the presence of genuine LGE. This could reduce ambiguity in reports. MethodsShort-axis, phase-sensitive inversion recovery late gadolinium images were extracted from our clinical cardiac magnetic resonance (CMR) database and shuffled. Two, independent, blinded experts scored each individual slice for “LGE likelihood” on a visual analog scale, from 0 (absolute certainty of no LGE) to 100 (absolute certainty of LGE), with 50 representing clinical equipoise. The scored images were split into two classes—either “high certainty” of whether LGE was present or not, or “low certainty.” The dataset was split into training, validation, and test sets (70:15:15). A deep learning binary classifier based on the EfficientNetV2 convolutional neural network architecture was trained to distinguish between these categories. Classifier performance on the test set was evaluated by calculating the accuracy, precision, recall, F1-score, and area under the receiver operating characteristics curve (ROC AUC). Performance was also evaluated on an external test set of images from a different center. ResultsOne thousand six hundred and forty-five images (from 272 patients) were labeled and split at the patient level into training (1151 images), validation (247 images), and test (247 images) sets for the deep learning binary classifier. Of these, 1208 images were “high certainty” (255 for LGE, 953 for no LGE), and 437 were “low certainty”. An external test comprising 247 images from 41 patients from another center was also employed. After 100 epochs, the performance on the internal test set was accuracy = 0.94, recall = 0.80, precision = 0.97, F1-score = 0.87, and ROC AUC = 0.94. The classifier also performed robustly on the external test set (accuracy = 0.91, recall = 0.73, precision = 0.93, F1-score = 0.82, and ROC AUC = 0.91). These results were benchmarked against a reference inter-expert accuracy of 0.86. ConclusionDeep learning shows potential to automate quality control of late gadolinium imaging in CMR. The ability to identify short-axis images with intermediate LGE likelihood in real-time may serve as a useful decision-support tool. This approach has the potential to guide immediate further imaging while the patient is still in the scanner, thereby reducing the frequency of recalls and inconclusive reports due to diagnostic indecision.

Performance of European and American Societies of Gastrointestinal Endoscopy Guidelines for Prediction of Choledocholithiasis in Patients with Acute Biliary Pancreatitis.

Background and Objectives: Up to one-third of patients with acute biliary pancreatitis also present with choledocholithiasis. Guidelines from the European Society of Gastrointestinal Endoscopy (ESGE) and the American Society for Gastrointestinal Endoscopy (ASGE) for investigating suspected choledocholithiasis suggest endoscopic retrograde cholangiopancreatography in patients with high-likelihood (ESGE)/high-probability (ASGE) predictors and endoscopic ultrasound in those with intermediate-likelihood (ESGE)/intermediate-probability (ASGE) predictors. Although both guidelines are similar, they are not identical. Furthermore, these algorithms were mainly developed from cohorts of patients without pancreatitis and are therefore poorly validated in a subset of patients with acute pancreatitis. We aimed to assess the performance of the ESGE and ASGE algorithms for the prediction of choledocholithiasis in patients with acute biliary pancreatitis. Materials and Methods: This was a retrospective analysis of 86 consecutive patients admitted to a tertiary referral centre in the year 2020 due to acute biliary pancreatitis. Results: Choledocholithiasis was confirmed in 29/86 (33.7%) of patients (13 with endoscopic retrograde cholangiopancreatography and 16 with endoscopic ultrasound). All 10/10 (100%) ESGE high-likelihood and 14/19 (73.7%) ASGE high-probability patients had choledocholithiasis. Only 19/71 (26.8%) patients with ESGE intermediate likelihood and 15/67 (22.4%) with ASGE intermediate probability had choledocholithiasis. Only 8/13 (61.5%) patients with the ASGE high-probability predictor of dilated common bile duct plus bilirubin > 68.4 µmol/mL had choledocholithiasis. Since this predictor is not considered high likelihood by ESGE, this resulted in a superior specificity of the European compared to the American guideline (100% vs. 91.2%). Following the American instead of the European guidelines would have resulted in five unnecessary endoscopic retrograde cholangiopancreatographies and five unnecessary endoscopic ultrasound examinations. Conclusions: This retrospective analysis suggests that the European guidelines may perform better than the American guidelines at predicting choledocholithiasis in the setting of acute pancreatitis. This was because dilated common bile duct plus bilirubin > 68.4 µmol/mL was not a reliable predictor for persistent bile duct stones.

Reduction of perivascular inflammation following long-term statin treatment - a coronary CT follow-up study using Fat Attenuation Index

Abstract Background Perivascular fat attenuation index (FAI) assessed by coronary computed tomography (CCTA) has been demonstrated to represent a reliable marker of coronary inflammation. Several studies have explored the potential anti-inflammatory effects of statins in reducing the risk of plaque rupture and subsequent cardiovascular events. However, the effect of statin therapy on FAI has not been clearly demonstrated so far. Purpose Our objective was to investigate the changes in perivascular FAI at the level of coronary lesions, as measured by coronary computed tomography (CCTA), following long-term high-dose statin therapy. Methods This study includes 23 patients who presented with typical chest pain, had a low to intermediate likelihood of coronary artery disease, and underwent a CCTA examination which revealed the existence of at least one coronary atheromatous plaque. Statin therapy was initiated in all patients according to guidelines. The CCTA was repeated after a time interval ranging from 1.5 to 3 years. Lesion-specific perivascular FAI, together with different plaque characteristics, were measured at both baseline and follow-up using a new AI-powered medical device called CaRi-Heart®. Results The mean age of the participants was 61.72 ± 8.86 at the time of the first scan, and 65.21% (n = 15) of them were male. At baseline, the CT density of the adipose tissue (ranging from -190 to -30 HU), was not significantly different between the two groups. A significant decrease in serum lipids following statin therapy was recorded during follow-up: from 193.4 ± 47.09 to 145.2 ± 34.7, p = 0.04 for total cholesterol, and from 101.77 ± 25.20 to 86.41 ± 21.09, p = 0.02 for LDL cholesterol. The FAI-score consistently decreased from baseline to follow-up, especially in the left anterior descending artery: from 15.87 ± 9.32 vs. 12.40 ± 7.55, p = 0.04, while there was no significant decrease in coronary inflammation at the level of left circumflex artery (13.98 ± 6.16 vs. 13.10 ± 6.59, p = ns), or right coronary artery (20.53 ± 13.74 vs. 19.96 ± 16.24, p = ns). Similarly, the FAI-Score Centile values were lower during the second scan, specifically for LAD (0.51 ± 0.28 vs. 0.69 ± 0.29, p = 0.04), while there were no significant differences of FAI score centile in the LCX (0.72 ± 0.28 vs. 0.74 ± 0.26, p = ns) and RCA (0.71 ± 0.32 vs. 0.78 ± 0.21, p = ns). Conclusion CaRi-Heart® mapping technology revealed a significant decrease of coronary inflammation, as expressed by the FAI-score, as a result of high-dose statin treatment especially at the level of the LAD. This indicates a potential role of local factors related to coronary circulation in the complex process of plaque inflammation. The perivascular FAI-score and FAI-score centile may serve as promising imaging biomarkers for monitoring the anti-inflammatory response to statin treatments.Color-coded FAI MappingPVAT-FAI Score of Coronary Inflammation

Repeatability of MRI Biomarkers in Nonalcoholic Fatty Liver Disease: The NIMBLE Consortium.

Background There is a need for reliable noninvasive methods for diagnosing and monitoring nonalcoholic fatty liver disease (NAFLD). Thus, the multidisciplinary Non-invasive Biomarkers of Metabolic Liver disease (NIMBLE) consortium was formed to identify and advance the regulatory qualification of NAFLD imaging biomarkers. Purpose To determine the different-day same-scanner repeatability coefficient of liver MRI biomarkers in patients with NAFLD at risk for steatohepatitis. Materials and Methods NIMBLE 1.2 is a prospective, observational, single-center short-term cross-sectional study (October 2021 to June 2022) in adults with NAFLD across a spectrum of low, intermediate, and high likelihood of advanced fibrosis as determined according to the fibrosis based on four factors (FIB-4) index. Participants underwent up to seven MRI examinations across two visits less than or equal to 7 days apart. Standardized imaging protocols were implemented with six MRI scanners from three vendors at both 1.5 T and 3 T, with central analysis of the data performed by an independent reading center (University of California, San Diego). Trained analysts, who were blinded to clinical data, measured the MRI proton density fat fraction (PDFF), liver stiffness at MR elastography (MRE), and visceral adipose tissue (VAT) for each participant. Point estimates and CIs were calculated using χ2 distribution and statistical modeling for pooled repeatability measures. Results A total of 17 participants (mean age, 58 years ± 8.5 [SD]; 10 female) were included, of which seven (41.2%), six (35.3%), and four (23.5%) participants had a low, intermediate, or high likelihood of advanced fibrosis, respectively. The different-day same-scanner mean measurements were 13%-14% for PDFF, 6.6 L for VAT, and 3.15 kPa for two-dimensional MRE stiffness. The different-day same-scanner repeatability coefficients were 0.22 L (95% CI: 0.17, 0.29) for VAT, 0.75 kPa (95% CI: 0.6, 0.99) for MRE stiffness, 1.19% (95% CI: 0.96, 1.61) for MRI PDFF using magnitude reconstruction, 1.56% (95% CI: 1.26, 2.07) for MRI PDFF using complex reconstruction, and 19.7% (95% CI: 15.8, 26.2) for three-dimensional MRE shear modulus. Conclusion This preliminary study suggests that thresholds of 1.2%-1.6%, 0.22 L, and 0.75 kPa for MRI PDFF, VAT, and MRE, respectively, should be used to discern measurement error from real change in patients with NAFLD. ClinicalTrials.gov registration no. NCT05081427 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Kozaka and Matsui in this issue.

Increased risk of coronary plaque vulnerabilization following COVID-19 infection, identified by elevated FAI index of pericoronary inflammation at coronary CT

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This research has been funded by the research grant Intel-FAT, proposal registration code PN-III-P4-ID-PCE-2020-2861, contract number PCE 206/2021, Project funded by the European Union and the Government of Romania through the Ministry of European Funds, and the Doctoral School of the “George Emil Palade” University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, Romania. Background Inflammation plays an essential role in all stages of atherosclerosis, with stable plaques characterized by chronic inflammation and vulnerable or ruptured plaques exhibiting "active" inflammation. COVID infection may significantly increase systemic inflammation, but the role of SARS COV-2 infection on local plaque vulnerability is still not elucidated. Mapping the PCAT - FAI on routine CCTA can detect coronary artery inflammation non-invasively by measuring changes in the composition of pericoronary fat. Purpose The aim of this study was to assess the impact of COVID-19 infection on CAD in patients who underwent CCTA examinations for chest pain in the early stages after infection, using the new AI - powered CaRi-Heart® solution. Methods In our study, we included 158 patients (mean age was 61.63 ± 10.14 years) with chest pain and low to intermediate clinical likelihood of CAD, who underwent 128-slice CCTA for assessment of coronary anatomy, atherosclerosis, and determination of FAI – Score. The study population was divided into two main groups: Group 1 (n = 75) – patients who had a COVID-19 infection a few months prior to their CCTA examination, and Group 2 (n = 83) – patients adjusted for age and gender, who did not have a COVID-19 infection. Results The FAI - Score was consistently higher in the non COVID-19 group: LAD (11.61 ± 7.60 vs. 9.32 ± 6.00, p = 0.05), LCX (12.43 ± 6.65 vs. 10.48 ± 6.24, p = 0.05), RCA (15.40 ± 11.36 vs. 14.54 ± 12.17, p = ns), the average FAI - Score (12.81 ± 8.28 vs. 10.47 ± 7.19, p = 0.001). For the FAI-Score Centile, the overall pattern shifts significantly, as the values for all three coronary arteries are higher for the subjects in the COVID-19 positive group, as follows: LAD (0.66 ± 0.29 vs. 0.58 ± 0.28, p = 0.05), LCX (0.79 ± 0.16 vs. 0.68 ± 0.26, p = 0.03), RCA (0.83 ± 0.20 vs. 0.68 ± 0.29, p = 0.05). In both cases, the CaRi Heart® Risk (p < 0.0001) and the Duke Score (p < 0.0001) had significantly higher values for the patients in the COVID-negative group. Conclusion Lesions with higher pericoronary FAI - Score Centile values were more commonly found in patients who had previously been infected with COVID-19. The higher levels of inflammation in the pericoronary adipose tissue suggests that COVID-19 infection is linked to an increased risk of coronary plaque destabilization.

Regional distribution of pericoronary inflammation in post COVID-19 patients - an angio-CT study of epicardial fat attenuation

Abstract Funding Acknowledgements Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This work was supported by the George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Research Grant number 164/20/10.01.2023. Background Epicardial fat (EF) and pericoronary adipose tissue (PCAT) have been extensively studied in the last decade as markers and promotors of local coronary inflammation. Quantification of EF and PCAT via CCTA, can predict the risk of acute events across various cardiovascular disorders, and has been linked to markers of local or systemic inflammation. Mapping the fat attenuation index (FAI) on routine CCTA can detect coronary artery inflammation at different levels of the coronary tree. Objectives This study aimed to evaluate the regional differences between left and right coronary inflammation in patients who had CCTA examinations for chest pain in the early stages after COVID-19 infection COVID-19 infection, using the AI-powered CaRi-Heart® medical software. Methods In this study, we included 172 patients (mean age: 62.43 ± 11.62 years) with chest pain and low to intermediate clinical likelihood of CAD, who underwent 128-slice CCTA to assess coronary anatomy, atherosclerosis, and FAI – Score determination. The study population was divided into two groups: Group 1 (n = 80) – with COVID-19 infection 2–3 months prior to their CCTA examination, Group 2 (n = 92) – adjusted for age and gender, without COVID-19 infection. For each patient, we recorded and analyzed demographic and clinical characteristics, cardiovascular risk factors, and the onset of signs and symptoms before the CCTA examination. Results The FAI - Score was considerably higher in the non COVID-19 group: LAD (11.87 ± 8.23 vs. 9.12 ± 6.20, p = 0.05), LCX (13.02 ± 6.76 vs. 10.77 ± 6.13, p = 0.05), RCA (15.88 ± 10.36 vs. 14.74 ± 12.24, p = ns), the average FAI - Score (13.23 ± 8.92 vs. 10.34 ± 7.22, p = 0.001). Comparing the FAI - Score between the left and right coronary artery, we found that for the entire study population, the FAI score was significantly higher at the RCA level (15.23 ± 11.97 vs. 11.21 ± 6.98, p = 0.02), and this difference was also maintained in the COVID-19 positive group (14.54 ± 12.17 vs. 9.77 ± 5.94, p = 0.0002), but not in the non-COVID-19 group (14.20 ± 10.78 vs. 12.88 ± 7.41, p = ns). In both groups, the CaRi Heart® Risk (p < 0.0001) and Duke Score (p < 0.0001) were significantly higher for the COVID-negative patients. Conclusions COVID-19 infection is associated with a higher risk of coronary plaque destabilization, as shown by increased inflammation in the PCAT. For the entire study population, the FAI - Score was significantly higher at the RCA level, the difference being driven by the increased RCA inflammation in the post-COVID group. This indicates a potential role of local hemorheological factors in the complex process of inflammation-mediated plaque vulnerabilization.

Using Bayesian updating for monopile offshore wind turbines monitoring

Digital twins (DTs) are thought to be promising tools for offshore wind turbines (OWTs) in real-time updating, optimized design, intelligent operation, and maintenance. When creating DT analysis tools, it is critical to update model parameters to create high-fidelity, high-accuracy virtual models. In this paper, a Bayesian updating framework based on Transitional Markov Chain Monte Carlo (TMCMC) is proposed to construct the desired virtual model of monopile OWTs to address this difficult problem. The likelihood function for Bayesian inference was created using measurements from physical entity monitoring as well as natural frequencies and damping ratios from the monopile OWT finite element (FE) model. Then, through a series of relatively simple intermediate likelihood functions, it gradually converges to the target function. During this time, the artificial neural network (ANN) surrogate model calculates the intermediate likelihood function of each sample, and a parallel computing strategy is used to enhance the computational efficiency. The results show that the posterior distribution of the uncertain parameters can be successfully estimated from the Markov chain using this method to update the finite element model. In addition, the proposed Bayesian updating method is resistant to measurement noise.

CT CORONARY ANGIOGRAPHY AS THE INITIALANATOMIC IMAGING TEST FOR STABLE CHEST PAIN

Coronary artery disease (CAD) is the leading cause of morbidity and mortality in the current scenario. The recommended diagnostic protocols include either exercise treadmill testing (ETT) or noninvasive cardiac imaging tests like, stress echocardiography (SE), myocardial perfusion scintigraphy (MPS), and coronary computed tomographic angiography (CCTA) to diagnose, prognosticate risk and impact therapeutic decision making for patients with an intermediate pre-test likelihood of stable CAD. In comparison with cardiac testing without imaging, non-invasive cardiac testing with imaging has been favoured as an initial test for stable angina patients with at least intermediate pre-test likelihood of obstructive CAD, due to its superior ability to diagnose, reclassify and predict CAD events, guiding the [1] subsequent treatment

Elevated FAI Index of Pericoronary Inflammation on Coronary CT Identifies Increased Risk of Coronary Plaque Vulnerability after COVID-19 Infection.

Inflammation is a key factor in the development of atherosclerosis, a disease characterized by the buildup of plaque in the arteries. COVID-19 infection is known to cause systemic inflammation, but its impact on local plaque vulnerability is unclear. Our study aimed to investigate the impact of COVID-19 infection on coronary artery disease (CAD) in patients who underwent computed tomography angiography (CCTA) for chest pain in the early stages after infection, using an AI-powered solution called CaRi-Heart®. The study included 158 patients (mean age was 61.63 ± 10.14 years) with angina and low to intermediate clinical likelihood of CAD, with 75 having a previous COVID-19 infection and 83 without infection. The results showed that patients who had a previous COVID-19 infection had higher levels of pericoronary inflammation than those who did not have a COVID-19 infection, suggesting that COVID-19 may increase the risk of coronary plaque destabilization. This study highlights the potential long-term impact of COVID-19 on cardiovascular health, and the importance of monitoring and managing cardiovascular risk factors in patients recovering from COVID-19 infection. The AI-powered CaRi-Heart® technology may offer a non-invasive way to detect coronary artery inflammation and plaque instability in patients with COVID-19.

Indian Survey on Management of Choledocholithiasis—Opportunities for Improvement and Future Studies

Abstract Background In clinical practice, decision about management of choledocholithiasis is driven by availability of resources and expertise, patients and healthcare professional preferences. This survey is aimed to describe the approach of physicians and surgeons for the management of choledocholithiasis. Method A 36-question online survey was conducted using Google Forms on various aspects of management of choledocholithiasis. Results The responses from 323 participants were included, of which 202 (62.54%) were physicians and 121 (37.46%) were surgeons. The proportion of responders who do not follow American or European Society of Gastrointestinal Endoscopy guidelines is associated with increasing age and experience of responders (p = 0.0001), while place of work (private vs. teaching) and broad specialty (physician vs surgeon) are not associated (p >0.05). For patients with high likelihood of choledocholithiasis, 123 (38.1%) participants prefer to do endoscopic ultrasound/magnetic resonance cholangiopancreatography (EUS/MRCP) rather than directly performing endoscopic retrograde cholangiopancreatography/intraoperative cholangiography (ERCP/IOC). For intermediate likelihood, MRCP is more commonly preferred compared with EUS, due to local availability (44%), expertise (39.6%), healthcare professionals preference (30.7%), and patients preference (17.3%). For difficult common bile duct (CBD) stones, short biliary sphincterotomy with large balloon sphincteroplasty (59.4%), followed by laparoscopic CBD exploration are commonly used approaches. Prophylactic CBD stent placement after ERCP and CBD clearance is common practice. Preoperative ERCP followed by cholecystectomy is more preferred approach than cholecystectomy and CBD exploration. Conclusion There is considerable variability in the management of choledocholithiasis. The practices such as use of EUS/MRCP for high likelihood group, use of prophylactic CBD stent placement after ERCP and CBD clearance, and use of single stage approach especially in patient with intermediate likelihood group should be addressed in future studies.

Neuropathology in the LifeAfter90 Study: Update on an Ethnically Diverse Cohort Study of Oldest‐Old

AbstractBackgroundNeuropathology studies of the oldest‐old have significantly advanced our understanding of the multiple etiologies late in very late life; however, this has been limited to studies of oldest‐old non‐Hispanic white (NHW) decedents. Our goal was to characterize neuropathology in a cohort of diverse oldest‐old decedents.MethodThe Life after 90 study is an ongoing cohort study of members of Kaiser Permanente Northern California, aged 90+ with targeted recruitment of individuals across different racial/ethnic groups with no prior diagnosis of dementia in their medical record. Participants are examined on average every 6 months. Brain donation was available to all interested consenting participants. Neuropathology was assessed using the National Alzheimer’s Coordinating Center Neuropathology form v. 10.ResultAs of January 2022, 216 participants (26% of sample) were enrolled in autopsy (autopsy enrollees: 20% Asian, 15% African American, 17% Latino, 9% Multiracial/Other, and 39% NHW) with 25 deceased and neuropathological evaluations completed. Average age of death was 95 years (range 91‐106), 13 (62.5%) were female, 6 Latino, 14 NHW, 3 Multiracial, 1 Asian, and 1 African American. At final clinical exam, 3 participants had dementia (12%), 8 questionable/mild cognitive impairment (32%), and 14 were cognitively normal (56%). With respect to Alzheimer’s disease (AD) neuropathologic diagnosis, 8 met criteria for intermediate likelihood (32%), 11 low (44%), and 6 did not have AD (24%); none had high AD likelihood. All participants had some level of neurofibrillary tangles (NFTs); median Braak NFT stage was II (range I‐V). Six participants lacked plaques, and highest Thal phase was 4. Eleven participants (44%) had Lewy bodies. Hippocampal sclerosis was seen in 1 participant, whereas TDP‐43 inclusions were detected in 5 (20%). Cerebral amyloid angiopathy was seen in 13 participants (25%). The most common assessed pathologies were age related tau astrogliopathy in 19 participants (76%) and some degree of arteriolosclerosis in 24 participants (96%) although only 4 were considered to have severe arteriolosclerosis.ConclusionThis diverse cohort of oldest‐old individuals indicate numerous brain pathologies are present with advanced age, albeit most participants having mild severity and distributions of pathologies providing further evidence of the complex and multifactorial nature of clinic‐pathological correlations.

Radiomics-based analysis by machine learning techniques improves characterization of functionally significant coronary lesions

Abstract Background Computed Tomography Coronary Angiography (CTCA) is an effective non-invasive imaging modality for anatomo-functional assessment of coronary artery disease (CAD). Radiomics features have been used for diagnosis or outcome prediction, however, their potential value for characterizing flow limiting coronary lesions has not been explored. Purpose To assess whether application of novel radiomics and machine learning (ML) techniques on CTCA derived datasets improves characterization of functionally significant coronary lesions. Methods Consecutive patients with stable chest pain and intermediate pre-test likelihood for CAD, who underwent CTCA and PET-or SPECT-Myocardial Perfusion Imaging (MPI) respectively, were prospectively evaluated and included in the analysis. PET-MPI was considered abnormal when >1 contiguous segments showed both stress Myocardial Blood Flow ≤2.3mL/g/min and Myocardial Flow Reserve (MFR) ≤2.5 for 15O-water or <1.79 mL/g/min and ≤2.0 for 13N-ammonia respectively. Defect reversibility (DR) was defined as a summed difference score (SDS) between stress and rest images ≥2. CTCA and functional images were fused to assign each myocardial segment to the pertinent coronary territory. Stenosis severity, plaque characteristics and radiomic plaque features were assessed in the total length of the 3 main coronary vessels. In total, 1765 features were extracted from each vessel and a feature reduction and model creation pipeline was constructed [Figure 1]. Two separate datasets: a) coronary stenosis (≥50%) + plaque characteristics and b) coronary stenosis (≥50%) + plaque characteristics + radiomics were formulated and compared in terms of AUCs accordingly. Results A total of 292 coronary vessels (140 with corresponding PET-MPI data and 152 with SPECT MPI data) were analysed. Plaque burden and stenosis severity were the only independent predictors of impaired myocardial perfusion on PET-MPI, with an AUC = 0.749, (95% CI: 0.658–0.826). Stenosis severity, kurtosis, contrast, interquartile range and entropy were predictors of an abnormal PET-MPI result and their combination resulted in an AUC = 0.854, (95% CI: 0.775–0.914). The difference between the 2 models was statistically significant (p-diff: 0.02, 95% CI: 0.0165–0.194). Stenosis severity was the only predictor of a DR on SPECT-MPI, AUC = 0.624 (95% CI: 0.542–0.702). Small Dependence High Gray Level Emphasis, Cluster Prominence, Region Length, wavelet Median and square Median were predictors of a positive SPECT result, with AUC = 0.816, (95% CI: 0.745–0.875). The difference between the two models was statistically significant (p-diff: 0.006, 95% CI: 0.152–0.329) Conclusion Radiomic futures can be combined with anatomical and morphological characteristics of coronary lesions in CTCA imaging and provide valuable complementary information for characterizing functionally significant coronary lesions. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): This work was supported from European Regional Development Fund, Operational Programme “Competitiveness, Entrepreneurship and Innovation 2014-2022 (EPAnEK)”, titled: The Greek Research Infrastructure for Personalized Medicine (pMED-GR)

Role of endoscopic ultrasound in evaluation of patients with missed common bile duct stones

BACKGROUNDCholedocholithiasis develops in up to 20% of patients with gall bladder stones. The challenge in diagnosis usually occurs with small stones that may be missed by magnetic resonance cholangiopancreatography (MRCP). Endoscopic ultrasound (EUS) is accurate in detecting common bile duct (CBD) stones missed by MRCP, especially the small ones or those impacted at the distal CBD or the papillary region. AIMTo evaluate the accuracy of EUS in detecting CBD stones missed by MRCP. METHODSPatients with an intermediate likelihood of choledocholithiasis according to ESGE guidelines and those with acute pancreatitis of undetermined cause were included. The presence of choledocholithiasis was evaluated by MRCP and EUS, and then results were confirmed by endoscopic retrograde cholangiopancreatography (ERCP). The sensitivity and specificity of EUS and MRCP were compared regarding the presence of stones, the size, and the number of detected stones. RESULTSNinety out of 100 involved patients had choledocholithiasis, while ten patients were excluded as they had pancreatic or gall bladder masses during EUS examination. In choledocholithiasis patients, the mean age was 52.37 ± 14.64 years, and 52.2% were males. Most patients had biliary obstruction (74.4%), while only 23 (25.6%) patients had unexplained pancreatitis. The overall prevalence of choledocholithiasis was 83.3% by EUS, 41.1% by MRCP, and 74.4% by ERCP. Also, the number and size of CBD stones could be detected accurately in 78.2% and 75.6% by EUS and 41.1% and 70.3% by MRCP, respectively. The sensitivity of EUS was higher than that of MRCP (98.51% vs 55.22%), and their predictive value was statistically different (P < 0.001). Combination of both tools raised the sensitivity to 97.22% and specificity to 100%. CONCLUSIONEUS could be a useful tool in assessing patients with suspected choledocholithiasis especially if combined with MRCP. However, its usefulness depends on its availability and the experience of the local centers.

Assessment of a Plasma Amyloid Probability Score to Estimate Amyloid Positron Emission Tomography Findings Among Adults With Cognitive Impairment

The diagnostic evaluation for Alzheimer disease may be improved by a blood-based diagnostic test identifying presence of brain amyloid plaque pathology. To determine the clinical performance associated with a diagnostic algorithm incorporating plasma amyloid-β (Aβ) 42:40 ratio, patient age, and apoE proteotype to identify brain amyloid status. This cohort study includes analysis from 2 independent cross-sectional cohort studies: the discovery cohort of the Plasma Test for Amyloidosis Risk Screening (PARIS) study, a prospective add-on to the Imaging Dementia-Evidence for Amyloid Scanning study, including 249 patients from 2018 to 2019, and MissionAD, a dataset of 437 biobanked patient samples obtained at screenings during 2016 to 2019. Data were analyzed from May to November 2020. Amyloid detected in blood and by positron emission tomography (PET) imaging. The main outcome was the diagnostic performance of plasma Aβ42:40 ratio, together with apoE proteotype and age, for identifying amyloid PET status, assessed by accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). All 686 participants (mean [SD] age 73.2 [6.3] years; 368 [53.6%] men; 378 participants [55.1%] with amyloid PET findings) had symptoms of mild cognitive impairment or mild dementia. The AUC of plasma Aβ42:40 ratio for PARIS was 0.79 (95% CI, 0.73-0.85) and 0.86 (95% CI, 0.82-0.89) for MissionAD. Ratio cutoffs for Aβ42:40 based on the Youden index were similar between cohorts (PARIS: 0.089; MissionAD: 0.092). A logistic regression model (LRM) incorporating Aβ42:40 ratio, apoE proteotype, and age improved diagnostic performance within each cohort (PARIS: AUC, 0.86 [95% CI, 0.81-0.91]; MissionAD: AUC, 0.89 [95% CI, 0.86-0.92]), and overall accuracy was 78% (95% CI, 72%-83%) for PARIS and 83% (95% CI, 79%-86%) for MissionAD. The model developed on the prospectively collected samples from PARIS performed well on the MissionAD samples (AUC, 0.88 [95% CI, 0.84-0.91]; accuracy, 78% [95% CI, 74%-82%]). Training the LRM on combined cohorts yielded an AUC of 0.88 (95% CI, 0.85-0.91) and accuracy of 81% (95% CI, 78%-84%). The output of this LRM is the Amyloid Probability Score (APS). For clinical use, 2 APS cutoff values were established yielding 3 categories, with low, intermediate, and high likelihood of brain amyloid plaque pathology. These findings suggest that this blood biomarker test could allow for distinguishing individuals with brain amyloid-positive PET findings from individuals with amyloid-negative PET findings and serve as an aid for Alzheimer disease diagnosis.

Evaluating the presence of domestic cat hepadnavirus viraemia in cats with biochemical alterations suggestive of liver disease.

The association between domestic cat hepadnavirus (DCH) infection and feline chronic hepatitis and hepatocellular carcinoma has been suggested. However, studies focused on the association between DCH infection and clinicopathological changes consistent with liver disease in cats are not available. This retrospective investigation included sera obtained from 96 cats that had the serum activity of at least alanine aminotransferase or alkaline phosphatase measured during initial diagnostic work-up. Based on these haematobiochemical results, cats were categorised according to their likelihood of having liver disease (absent, low, intermediate or high). DCH DNA was detected using real-time PCR, nested PCR and sequencing. Overall, potential liver damage was observed in 44 cats, including cats with low (n=14), intermediate (n=10) and high (n=20) likelihood of liver disease. Four cats (4.2%) were DCH-positive, with three positive cats belonging to the liver disease group (two with low and one with intermediate likelihood of liver disease). Although the pathogenic potential of DCH in cats still has to be clarified, these results suggest that DCH testing should not be based only on the presence of biochemical changes potentially consistent with liver disease.

Host parent responses to heterospecific parasite nestling alarm calls are independent of past and current experience with experimental brood parasitism

Communication between parents and dependent offspring is critical not only during provisioning, but also in antipredator contexts. In altricial birds, a top cause of reproductive failure is nest predation, and alarm calls both by parents and chicks can serve to alert others and increase the likelihood of offspring escaping predation. Understanding the factors that determine the strength of parental antipredator responses to different nestling alarm calls can provide insight into parent-offspring recognition. The prothonotary warbler (Protonotaria citrea), a host of the obligate brood parasite, the brown-headed cowbird (Molothrus ater), never rejects cowbird young and raises the parasite together with its own offspring. To determine whether warbler parents learn cowbird nestling alarm calls, we presented experimentally parasitized or non-parasitized parents with playbacks of conspecific warbler, parasitic cowbird, and a harmless heterospecific control, eastern bluebird (Sialis sialis), nestling alarm calls. We recorded the latency to respond and the number of chips given by members of the resident warbler pair. We found that parents were most likely to respond to warbler nestling alarm calls, least likely to respond to bluebird calls, with a statistically intermediate likelihood of responding to cowbird calls. Critically, current and past parasitism status did not affect the likelihood of response to any playback or the number of chips given, however, currently parasitized parents had greater response latencies to playbacks than non-parasitized parents. These results suggest that warbler parents do not learn cowbird alarm calls from breeding experiences and, in turn, that cowbirds may employ a generalized, bet-hedging alarm call.

Compliance to endoscopic retrograde cholangiopancreatography according to current guidelines and adverse outcomes of suspected choledocholithiasis in an acute care setting.

Common bile duct (CBD) stones are common among patients who underwent cholecystectomy. However, few studies have investigated the compliance with the guidelines for the prediction of choledochlithiasis (CL). Therefore, we aim to study the compliance with the American Society for Gastrointestinal Endoscopy (ASGE) guidelines for the identification of CL in a major hospital in Saudi Arabia's capital. We conducted a retrospective chart review on adult patients admitted to emergency department at King Abdulaziz Medical City, Riyadh with gallstones between January 2016 and January 2019. Our data collection includes demographics and level of suspicion based on Transabdominal Ultrasound, liver function, amylase, and lipase tests. We then determined the likelihood of CL based on ASGE guidelines in order to assess the adherence to ASGE guidelines, the procedure's outcomes and adverse outcomes. We identified 826 patients who met the study's criteria: 384 (46.4%) were compliant, while 442 (53.6%) were non-compliant with ASGE guidelines. There was a significant association between compliance and the presence of stones on ERCP in high likelihood patients. 48 (21.3%) of total ERCP procedures among all the likelihoods had adverse outcomes. 13 (40.6%) of non-compliant ERCP performed in intermediate likelihood have experienced adverse outcomes. There was a significant association between having adverse outcomes and being non-complaint with ASGE guidelines. Despite ASGE guidelines' recommendations, a third of high likelihood cases and the majority of intermediate likelihood cases were non-compliant. Additionally, the current guidelines for the intermediate group are somewhat vague, giving ample leeway for patients to be placed in the intermediate group, which might subject them to unnecessary interventions. To conclude, there was a great lack of compliance with ASGE guidelines that is significantly associated with adverse outcomes. Hence, reassessing the current guidelines and monitoring healthcare facilities' compliance with the updated guidelines is highly recommended.

Research in Brief

Endoscopic ultrasound or magnetic resonance cholangiopancreatography (MRCP) have comparable results for the diagnosis of choledocholithiasis; the choice of test should be based on local expertise, availability of resources, and patient preference, according to new research. Nitin Jagtap and colleagues randomly assigned patients with intermediate likelihood of choledocholithiasis (as per the European Society of Gastrointestinal Endoscopy guidelines) to receive either endoscopic ultrasound (n=112) or MRCP (n=112).

Diagnostic sensitivity of endoscopic ultrasonography in patients with suspected choledocholithiasis

The likelihood of common bile duct stones can be prognosticated by various clinical predictors, however, the sensitivity and specificity of these factors are moderate. Endoscopic ultrasonography has been shown to be a semi-invasive precise test for the detection of common bile duct stones. Our aim was to assess the diagnostic accuracy of endoscopic ultrasonography in patients with suspected choledocholithiasis. Patients of this prospective study were categorized and divided into intermediate likelihood and high likelihood groups according to the clinical predictors defined by the American Society of Gastrointestinal Endoscopy (ASGE) guidelines and referred for linear endosonography. Endoscopic retrograde cholangiopancreatography (ERCP) was performed if needed. A total of 95 patients were assessed. Common bile duct stones were detected by endoscopic ultrasonography overall in 53 (56%) patients: 55% (39/71) in the intermediate likelihood and 58% (14/24) in the high likelihood group of patients. The detected common bile duct stones in all patients were confirmed by ERCP. There was no significant difference (p = 0.56) in the detection of stones by ERCP between the two likelihood groups. ERCP confirmed choledocholithiasis only in one patient whose preceding endosonography did not detect stone. The specificity and sensitivity of endoscopic ultrasonography were 100% and 98%, the positive predictive value and negative predictive value were 100% and 98%, respectively. Estimating the likelihood of choledocholithiasis based on various clinical predictors might be challenging. Endoscopic ultrasonography is a highly sensitive and accurate diagnostic tool for the detection and evaluation of common bile duct stones also in patients with previous normal imaging findings. Orv Hetil. 2022; 163(10): 400-406.