Discordant Findings Research Articles

“It’s all connected:” A mixed methods study of insomnia, stigma, and discrimination among individuals on medication for opioid use disorder

ObjectivesInsomnia is one of the most common sleep disorders among those with opioid use disorder (OUD), including those on medication for OUD. There is a dearth of literature exploring the role of social stressors on sleep outcomes among this group. The purpose of this study was to explore the association between OUD-related stigma and intersectional discrimination with insomnia among individuals on medication for OUD. MethodsParticipants were recruited from treatment clinics in the Northeast United States. Using a convergent mixed-methods research design, we explored associations with stigma (The Brief Opioid Stigma Scale), intersectional discrimination (Intersectional Discrimination Index), and insomnia (Insomnia Severity Index) through quantitative survey data and qualitative data from interviews for participant experiences. Data from the quantitative (n = 120) and qualitative (n = 25) components of the study were integrated for interpretation. ResultsQuantitative analysis indicated weak to moderate positive correlations between intersectional discrimination, and exploratory variables including pain, perceived stress, and psychological distress with insomnia severity. The qualitative analysis generated 4 main themes, which highlighted negative emotions and ruminations as factors that participants connected experiences with stigma and discrimination to poor sleep outcomes. Integration of data identified concordant and discordant findings. ConclusionsStigma, discrimination, physical symptoms, and psychological distress appear to contribute to poor sleep outcomes among those with OUD. Future research should target maladaptive outcomes of rumination and negative emotions to improve sleep outcomes among those with OUD.

The electrophysiological substrate of biopsy-proven cardiac amyloidosis

Abstract Background Cardiac amyloidoses (CA) are an increasingly recognized group of infiltrative cardiomyopathies associated with high risk of major adverse cardiac events. Endomyocardial biopsy (EMB) may be required to differentiate the amyloid type (mainly, Immunoglobulin light chain [AL] versus transthyretin-related [ATTR]) in some cases. Purpose The aim of this study was to provide the first description of the right ventricular (RV) electroanatomical substrate of CA, and assess its association with EMB findings and clinical outcomes. Methods We enrolled ten consecutive patients undergoing EMB for suspected CA (median age, 68[63-77]; male, 50%) in a monocentric, observational, retrospective study. All patients had a clinical diagnosis of CA, but a diagnosis of CA type was hampered by the presence of inconclusive or discordant laboratory-imaging findings (abnormal serum free light chain assay and positive bone scintigraphy, n=5; ambiguous imaging results, n=4; abnormal serum free light chain assay and TTR gene mutation, n=1). Therefore, each patient underwent RV high-density electroanatomical voltage mapping (EVM) and EMB. The primary outcome was death or hospitalization at 1-year follow-up. We recorded electrogram features at EMB sampling sites and in the overall RV, and explored their correlations with histopathological findings and primary outcomes events. Results A final EMB-proven diagnosis of AL or ATTR CA was formulated in 6 and 4 patients, respectively. Electrogram amplitudes in the bipolar and unipolar configurations averaged 1.58±0.65 mV, and 5.38±1.41 in the overall RV. We found a significant inverse correlation between unipolar electrogram amplitude and amyloid burden at EMB (p<0.001); the unipolar voltage cutoff that best identified regions with >15% amyloid tissue infiltration according to Youden index was 9.1 mV (sensitivity, 43%; specificity, 100%; accuracy, 77%). At 1-year follow-up, 6 patients (60%) experienced a primary outcome event. Compared to subjects with uneventful follow-up, patients with a primary outcome event had larger unipolar low-voltage zones (32.3 [6.1] cm2 vs. 20.7 [6.5] cm2, p=0.043) and bipolar dense scar areas (6.1 [2.3] cm2 vs. 1.8 [0.7] cm2, p=0.005), and after pooling mapping points from all patients, unipolar electrogram amplitude was moderately associated with primary outcome events (AUC: 0.65 [95% CI, 0.64-0.65]). Conclusions In CA, electrogram amplitudes are around the lower limit of normal, yet disproportionately low compared to the increased wall thickness. We found evidence that unipolar electrogram amplitude may be a quantitative marker of amyloid burden, possibly associated with adverse clinical outcomes.EVM and EMB in ATTR cardiac amyloidosisEVM and EMB in AL cardiac amyloidosis

Analysis of discordant PET and CT findings in 18F-FDG PET-CT scans in the management of oncology patients

Abstract Background: Discordant findings are often noted between PET-CT and CT images of 18F-FDG PET-CT scans and cause ambiguity in image interpretation.This study aimed at determining the significance of these findings in the management of oncology patients. Context: Discordant findings are often noted between PET-CT and CT images of 18F-FDG PET-CT scans and cause ambiguity in image interpretation. Aim: This study aimed at determining the significance of these findings in the management of oncology patients. Methods: This was an observational, descriptive study. Hence, retrospective analysis of all discordant findings in oncology patients undergoing a PETCT imaging between Jan 2013 and Jan 2016 was done. Those patients who had a follow-up period of minimum 1 year in either of the following forms – repeat PETCT imaging, other radiological imaging, clinical, or histopathological evidence were included. From all the discordant lesions, the sensitivity, specificity, positive predictive, negative predictive value, and accuracy of both PET-CT and CT modalities were determined. Results: Of 348 discordant lesions, 16.7% was noted in soft tissues, 25% in viscera, 28.7% in lungs, 14.1% in lymph nodes, and 15.5% in bones. At the end of follow-up, 15.2% lesions were PET true positive, 57.5% PET true negative, 10.1% CT true positive lesions, 13.8% CT true negative, and 3.4% were inconclusive. Conclusion: 18F-FDG PET-CT is superior to CT imaging and should be considered as the first-line imaging modality in oncology patients.

18-FDG PET-CT Scan Is a Good Tool to Detect Bone Marrow Involvement in Patients with Diffuse Large B-Cell Lymphoma: A Retrospective Analysis of 602 Patients

Background: Bone marrow biopsy is considered a gold standard to detect the involvement in lymphomas. Multi-color flow cytometry improves the detection of low-volume disease and is expected to increase the sensitivity over a BM Biopsy. These procedures are painful, expensive and with the widespread use of 18FDG PET-CT scan as the preferred staging scan, their utility is being re-evaluated. We analyzed the utility of BM studies, including multi-color flow cytometry in DLBCL and developed an algorithm to identify patients where it would be useful. Methods: This is a retrospective study from a tertiary care center in India conducted on patients registered from 01/2018 till 12/2019. De-novo patients aged ≥15 years with DLBCL who underwent their staging workup including both a PET-CT scan and BM studies were included for this analysis. Bone marrow studies include assessment by morphology, flow cytometry (optional) and biopsy. A 13-16 color multi-parameter flow cytometry (BD Fortessa) was used and 500,000 to 1 million events were acquired for the analysis. We recorded the baseline characteristics, Lugano staging and findings from the PET-CT scan and Bone marrow studies. The primary objective was to study the value of BM studies in altering the stage and management compared to a PET-CT scan. Additionally, the positive and negative predictive value of PET-CT scan, reasons for discordant findings, value of flow cytometry studies and impact of BM studies on the final prognostic index were analyzed. Results: A total of 698 DLBCL patients were registered during the period, 602(86%) of whom underwent both a PET-CT scan and Bone marrow studies. Flow cytometry was performed in 572 patients (95%). The median age was 52 years (15-82 years), 425 (70%) were male patients. The stage-wise distribution was; stage I-64(11%), stage II-118(20%), stage III- 74(12%) and stage IV- 346(57%) patients. The utility of PET-CT scan and BM studies in classifying a patient as stage IV is summarized in Table 1. BM studies upstaged a patient to stage IV in only 18 (3%) cases. In the absence of BM studies, these patients would be classified as stage I (4), stage II (4) and stage III (10) (Table 2). A change in prognosis would happen in only 4 of these patients due to a change in stage in 3 (stage I-1, stage II-2) and a change in NCCN-IPI from low-intermediate to high-intermediate in one patient. A change in treatment would occur in only 1 patient. The PPV and NPV of PET-CT for BM involvement using BM studies as a gold standard were 44.2% and 92.3% respectively. While 23/29 (79%) diffuse uptake on PET scan was detected by BM studies, only 35/102 (34%) focal uptake was detected by BM studies. The histological involvement was concordant in 63 patients, while 32 patients had a discordant histological finding. Flow cytometry alone was positive in 32(5.6%) patients, of which 27 patients were already classified as advanced stage (Stage III-7, Stage IV-20). Conclusions: Bone marrow studies, including flow cytometry can be avoided in patients with DLBCL who undergo a PET-CT scan. The additional value of BM studies from a prognostic or therapeutic view is too low to justify a regular use of this painful and expensive test.

81 An Examination of a Multiple Cutoff Performance Validity Index

Objective:Recent consensus guidelines have advocated for the use of multivariate performance validity assessment on ability-based measures such those used in neuropsychological assessment. Further, previous research has demonstrated that aggregating performance validity indicators may produce superior classification accuracy. The present study builds upon this research by aggregating data from three of the most commonly used performance validity measures (Test of Memory Malingering [TOMM], Rey Fifteen Item Test with recognition trial [FIT plus recognition], and Reliable Digit Span [RDS]) to create a performance validity composite measure in a veteran mild traumatic brain injury (mTBI) population.Participants and Methods:Data of patients evaluated at a VA hospital who had completed the RDS, FIT plus recognition, and TOMM as part of their clinical neuropsychological evaluation were analyzed (n = 20). Two composite performance validity indexes were created: a Single Cutoff Performance Validity Index (SC-PVI), which measures the quantity of failures across performance validity measures (PVMs) by summing the total number of PVM failures, and a Multiple Cutoff Performance Validity Index (MC-PVI) which measures the number of failures as well as degree of failure(s) across measures of performance validity (e.g., a participant would attain a score of 3 if their PVM performance failed to reach a conservative cut point; they would obtain a score of 1 if they met conservative cut point, yet failed to reach a liberal cut point).Results:Only one participant (5%) attained a score of 0 on the SC-PVI (i.e., passing all PVTs using standard cutoffs) and MC-PVI (i.e., passing the most liberal cut points on all three PVMs). Conversely, eight participants (40%) attained a score of 3 on the SC-PVI (i.e., failed all three PVMs) and four participants (20%) attained a score of 9 (i.e., failed the most conservative cut points on all three PVMs). Results showed a significant (p < .001) ordinal association between the two indices (G = .984); however, there was no significant agreement between SC-PVI and MC-PVI models (k = -.087; p = .127).Conclusions:Data revealed discordant findings between the three PVMs utilized. The majority of participants (75%) scored between 2-8 on the MC-PVI, meaning that they did not exceed all liberal cut points or fail all conservative cut points. These “grey area” scores suggest an indeterminate range of performance validity, which cannot be captured by a solitary cut point or neatly classified as pass or fail. The utility of multiple cutoff performance validity models (i.e., aggregating PVMs to consider the severity of failure and number of failures) is that they capture the nuance of these data when determining and discussing the credibility of a profile. Multiple cut point data also highlight how the choice of cutoff influences the outcome of performance validity research and clinical decision making. As such, future research on the classification accuracy of this MC-PVI is needed.

SAT181 Clinical Profile And Treatment Outcomes Of Patients With Sporadic And Multiple Endocrine Neoplasia Syndrome-related Primary Hyperparathyroidism

Abstract Disclosure: U.E. Mathew: None. V.P. Jyotsna: None. A.S. Upadhyay: None. A. Goyal: None. D. Kandaswamy: None. C. Bal: None. A. Sharma: None. C.K. Sharma: None. S. Aggarwal: None. N. Tandon: None. Primary hyperparathyroidism (PHPT) is the most frequent endocrine disorder in MEN-1. The MEN-1 related PHPT (MPHPT) differs from sporadic (SPHPT) in many aspects. The distinction between them is very important at the point of diagnosis as it enables planning on treatment and subsequent surveillance for other endocrine tumours. Objective: The aim of study was to compare the clinical, biochemical, radiological features and surgical outcome in patients with MPHPT versus SPHPT and to identify the predictors of MEN-1 among apparently sporadic hyperparathyroidism. Design: Ambispective cross-sectional study from 2015-2021. Participants: 251 subjects with SPHPT and 23 subjects with MPHPT. Setting: The endocrine clinic of All India Institute of Medical Sciences, New Delhi, India. Results: The classical symptoms of hyperparathyroidism (80.5% vs 47.8%, p<0.001), mean serum calcium (12.7 vs 11.8 mg/dl, p=0.01) and alkaline phosphatase (ALP) levels (p=0.03) were significantly seen higher in SPHPT than MPHPT. MEN-1 patients showed low bone mineral density (BMD) at lumbar spine (-1.52±1.44 vs -2.6±1.25, p=0.001) and femoral neck (1.13±1.37 vs-1.81±1.01, p=0.002) and higher prevalence of complicated nephrolithiasis (34.5 % vs 56.5%, p=0.03) for the age. BMD at their lumbar spine showed an inverse correlation with serum PTH (r=-0.51, p=0.01). Whereas the typical radiological features of hyperparathyroidism and severe skeletal manifestations including brown tumours and fractures were observed less in MEN-1 (44.8% vs 21.7% vs, p=0.02). The overall remission rate was 98.6% in SPHPT and 90% in MPHPT on long term follow up.Despite milder biochemical features, the frequency of hungry bone syndrome was not different from SPHPT (11.6% vs 15.8%, p=0.32). The transient and permanent hypoparathyroidism were more common in MPHPT group (24.4% vs 50%, p=0.01: 0.4% vs 15%, p=0.002).The factors strongly predictive of MEN-1 in multivariate analysis were ALP within the normal range (OR 4.2(95% CI 1.1-16.9), p=0.038), lower lumbar spine BMD (OR 0.47 (95% CI (0.28-0.76), p=0.003) and hyperplastic parathyroid gland on histopathology (OR 37.1(95% CI (9.9-138.6), p<0.001). The multivariate predictive model showed an excellent discrimination between two classes with area under curve in ROC was 0.91. Conclusions: MEN-1 associated PHPT have severe bone and renal involvement despite milder biochemical features, even in Indian settings, where there is a higher frequency of severe symptomatic sporadic hyperparathyroidism. MEN-1 should be suspected when, a discordant finding of severe degree of bone demineralisation at lumbar spine and in normal range of ALP, has observed among apparently SPHPT. Our model can assist in deciding on screening for MEN-1 as the family history and multiglandular involvement may be absent at the presentation, and delay in development of other endocrine tumours. Presentation: Saturday, June 17, 2023

S641 Characterization of Clinical and Manometric Features in Constipated Patients With Concordant vs Discordant Findings on Anorectal Function Testing

S641 Characterization of Clinical and Manometric Features in Constipated Patients With Concordant vs Discordant Findings on Anorectal Function Testing

Problem-solving Breast MRI.

Breast MRI has high sensitivity and negative predictive value, making it well suited to problem solving when other imaging modalities or physical examinations yield results that are inconclusive for the presence of breast cancer. Indications for problem-solving MRI include equivocal or uncertain imaging findings at mammography and/or US; suspicious nipple discharge or skin changes suspected to represent an abnormality when conventional imaging results are negative for cancer; lesions categorized as Breast Imaging Reporting and Data System 4, which are not amenable to biopsy; and discordant radiologic-pathologic findings after biopsy. MRI should not precede or replace careful diagnostic workup with mammography and US and should not be used when a biopsy can be safely performed. The role of MRI in characterizing calcifications is controversial, and management of calcifications should depend on their mammographic appearance because ductal carcinoma in situ may not appear enhancing on MR images. In addition, ductal carcinoma in situ detected solely with MRI is not associated with a higher likelihood of an upgrade to invasive cancer compared with ductal carcinoma in situ detected with other modalities. MRI for triage of high-risk lesions is a subject of ongoing investigation, with a possible future role for MRI in decreasing excisional biopsies. The accuracy of MRI is likely to increase with the use of advanced techniques such as deep learning, which will likely expand the indications for problem-solving MRI. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Effectiveness and safety of virtual reality rehabilitation after stroke: an overview of systematic reviews

Virtual reality (VR) is an innovative neurorehabilitation modality that has been variously examined in systematic reviews. We assessed VR effectiveness and safety after cerebral stroke. In this overview of systematic reviews, we searched eleven databases (Cochrane Database of Systematic Reviews, EMBASE, MEDLINE, SCOPUS, ISI Web of Science, CINAHL, PsycINFO, Pedro, Otseeker, Healthevidence.org, Epistemonikos) and grey literature from inception to January 17, 2023. Studies eligible for inclusion were systematic reviews published in English that included adult patients with a clinical diagnosis of stroke (acute to chronic phase) undergoing any kind of immersive, semi-immersive or non-immersive VR intervention with or without conventional therapy versus conventional therapy alone. The primary outcome was motor upper limb function and activity. The secondary outcomes were gait and balance, cognitive and mental function, limitation of activities, participation, and adverse events. We calculated the degree of overlap between reviews based on the corrected covered area (CCA). Methodological quality was assessed using the A MeaSurement Tool to Assess systematic Reviews (AMSTAR 2) and the Certainty of Evidence (CoE) using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. Discordances between results were examined using a conceptual framework based on the Jadad algorithm. This overview is registered with PROSPERO, CRD42022329263. Of the 58 reviews included (n=345 unique primary studies), 42 (72.4%) had conducted meta-analysis. More than half of the reviews (58.6%) were published between 2020 and 2022 and many (77.6%) were judged critically low in quality by AMSTAR 2. Most reported the Fugl Meyer Assessment scale (FMA-UE) to measure upper limb function and activity. For the primary outcome, there was a moderate overlap of primary studies (CCA 9.0%) with discordant findings. Focusing on upper limb function (FMA-UE), VR with or without conventional therapy seems to be more effective than conventional therapy alone, with low to moderate CoE and probable to definite clinical relevance. For secondary outcomes there was uncertainty about the superiority or no difference between groups due to substantial heterogeneity of measurement scales (eg, methodological choices). A few reviews (n=6) reported the occurrence of mild adverse events. Current evidence suggests that multiple meta-analyses agreed on the superiority of VR with or without conventional therapy over conventional therapy on FME-UE for upper limb. Clinicians may consider embedding VR technologies into their practice as appropriate with patient's goals, abilities, and preferences. However, caution is needed given the poor methodological quality of reviews. Italian Ministry of Health.

Analysis of Discordant Findings between 3T Magnetic Resonance Imaging and Arthroscopic Evaluation of the Knee Meniscus.

Numerous studies have assessed the performance of magnetic resonance imaging (MRI) in detecting tears of the knee menisci using arthroscopy results as the gold standard, but few have concentrated on the nature of discordant findings. The purpose of this study was to analyze the discordances between 3T MRI and arthroscopic evaluation of the knee meniscus. Medical records of 112 patients who underwent 3T MRI and subsequent arthroscopy of the knee were retrospectively analyzed to determine the accuracy of diagnoses of meniscal tear. Compared with arthroscopy, there were 22 false-negative and 14 false-positive MR interpretations of meniscal tear occurring in 32 patients. Images with errors in diagnosis were retrospectively reviewed by two musculoskeletal radiologists in consensus and all errors were categorized as either unavoidable, equivocal or as interpretation error. Of 36 MR diagnostic errors, there were 16 (44%) unavoidable, 5 (14%) interpretation errors and 15 (42%) equivocal for meniscal tear. The largest categories of errors were unavoidable false-positive MRI diagnoses (71%) and equivocal false-negative MRI diagnoses (50%). All meniscal tears missed by MRI were treated with partial meniscectomy (n = 14) or meniscal repair (n = 8). Discordant findings between 3T MRI and arthroscopic evaluation of the knee meniscus remain a concern and primarily occur due to unavoidable and equivocal errors. Clinicians involved in the diagnosis and treatment of patients with meniscal tears should understand why and how the findings seen on knee MRI and arthroscopy may sometimes differ.

Rejection! Or is it? Correlation among molecular microscope diagnostic system, histopathology and clinical judgement following heart transplantation

PurposeLittle is known about clinical decision making among discordant findings concerning for rejection with endomyocardial biopsy (EMBx) and Molecular Microscope Diagnostic System (MMDx) in patients following heart transplantation. MethodsTwo hundred and twenty-eight corresponding EMBx and MMDx specimens from 135 adult heart transplant patients were retrospectively reviewed. Rejection was classified as t-cell mediated rejection ≥2R and/or antibody mediated rejection ≥1. Clinical decision making among concordant and discordant cases of EMBx and MMDx results were reviewed. ResultsPatient characteristics were comparable between concordant and discordant patient groups (median age 60 yrs., 76% male, and 71% White). A total of 167/228 specimens (73%) were concordant for no rejection with 98% agreement in clinical decision making and 25/228 (11%) concordant for rejection with 64% agreement in clinical decision making. Among the 36/228 (16%) discordant samples, clinical decision-making agreed on treatment for rejection in five of the MMDx samples and three of the EMBx samples. ConclusionsMMDx can be an additional tool to diagnose rejection not detected by the traditional EMBx and influence clinical decision making in guiding appropriate treatment. Ongoing investigation into the clinical utility of MMDx is warranted to determine the significance of discordant findings among diagnostic modalities when assessing for rejection.

Scoping review of the association of plant-based diet quality with health outcomes.

The association of plant-based dietary patterns with health outcomes has traditionally been assessed without considering nutritional value. The plant-based dietary index (PDI), first published in 2016, overcomes this limitation with both a healthful PDI (hPDI) and an unhealthful PDI (uPDI), based on the quality of plant foods consumed plus the frequency of animal foods. We sought to summarize the breadth of research using the hPDI and uPDI to gain insight into how the quality of plant-based dietary patterns might be associated with health outcomes. Scoping review of studies that used the PDI, hPDI, or uPDI to report associations with health outcomes. Multiple databases were searched from 2010 through April 2023 with 2 authors independently assessing eligibility and extracting data. In addition to assessing the association of the indices to health outcomes, we determined the frequency of concordant or discordant findings for hPDI versus PDI and for hPDI versus uPDI. We included 95 articles (54% longitudinal, 37% cross-sectional, and 9% case-control) with a median sample size of 3,646. Higher hPDI levels were associated with favorable health outcomes in 36% of comparisons (most often for obesity, mortality, diabetes, cardiovascular disease, and psychiatric disorders), compared to 25% for the PDI and only 2% for the uPDI. Conversely, higher levels of the uPDI were associated with unfavorable health outcomes in 33% of comparisons, in contrast to under 1% for the hPDI and 2% for the PDI. When the hPDI association to an outcome was discordant with the uPDI or PDI, the significance and directionality always favored the hPDI over the uPDI, and nearly always favored the hPDI over the PDI. Dietary indices that account for the quality of plant foods can show health benefits that might be missed by a generic plant-based index. A greater focus on the quality of plant foods could improve nutrition guidelines, raise awareness about the benefits of adding unrefined plant foods to the diet, and empower consumers to make incremental additions of such foods to displace unhealthy foods. We anticipate increasing use of indices that address food quality in future research.

Added value of an artificial intelligence algorithm in reducing the number of missed incidental acute pulmonary embolism in routine portal venous phase chest CT.

The purpose of this study was to evaluate the incremental value of artificial intelligence (AI) compared to the diagnostic accuracy of radiologists alone in detecting incidental acute pulmonary embolism (PE) on routine portal venous contrast-enhanced chest computed tomography (CT). CTs of 3089 consecutive patients referred to the radiology department for a routine contrast-enhanced chest CT between 27-5-2020 and 31-12-2020, were retrospectively analysed by a CE-certified and FDA-approved AI algorithm. The diagnostic performance of the AI was compared to the initial report. To determine the reference standard, discordant findings were independently evaluated by two readers. In case of disagreement, another experienced cardiothoracic radiologist with knowledge of the initial report and the AI output adjudicated. The prevalence of acute incidental PE in the reference standard was 2.2% (67 of 3089 patients). In 25 cases, AI detected initially unreported PE. This included three cases concerning central/lobar PE. Sensitivity of the AI algorithm was significantly higher than the outcome of the initial report (respectively 95.5% vs. 62.7%, p < 0.001), whereas specificity was very high for both (respectively 99.6% vs 99.9%, p = 0.012). The AI algorithm only showed a slightly higher amount of false-positive findings (11 vs. 2), resulting in a significantly lower PPV (85.3% vs. 95.5%, p = 0.047). The AI algorithm showed high diagnostic accuracy in diagnosing incidental PE, detecting an additional 25 cases of initially unreported PE, accounting for 37.3% of all positive cases. Radiologist support from AI algorithms in daily practice can prevent missed incidental acute PE on routine chest CT, without a high burden of false-positive cases. • Incidental pulmonary embolism is often missed by radiologists in non-diagnostic scans with suboptimal contrast opacification within the pulmonary trunk. • An artificial intelligence algorithm showed higher sensitivity detecting incidental pulmonary embolism on routine portal venous chest CT compared to the initial report. • Implementation of artificial intelligence support in routine daily practice will reduce the number of missed incidental pulmonary embolism.

Discordant microsatellite instability findings in two samples from a patient with biliary cancer that responded to pembrolizumab.

Microsatellite instability (MSI) is a key marker to predict response to immune checkpoint inhibitors; however, only 1-2% of biliary cancers have this genomic feature. In a patient with hilar biliary cancer, MSI was examined in two cancer specimens (forceps biopsy from the biliary stricture and endoscopic ultrasound-guided fine-needle aspiration biopsy [EUS-FNAB] from the adjacent lymph node). We observed discordant results, as high frequency of MSI was found only in the forceps biopsy. Although the FNAB sample was 10 times larger than that of the forceps biopsy, the tumor concentration was much lower, which is a possible reason for the discordance. Besides, immunohistochemistry of four mismatch-repair (MMR) proteins showed proficient MMR expressions. The tumor became refractory to gemcitabine, cisplatin, and S-1 but responded well to pembrolizumab. Caution is needed for sample selection and for interpretation of the test's results, to avoid missing rare chance for effective molecular target agents.

Association of perceived and objective neighborhood walkability with accelerometer-measured physical activity and sedentary time in the Maastricht Study.

We investigated the association of neighborhood walkability with accelerometer-measured physical activity (PA) and sedentary behavior (SB) and examined whether objective and subjective measures of walkability resulted in similar findings. PA and SB from the first 7689 Maastricht Study participants ages 40-75 from 2010 to 2017 were measured using accelerometers for 7 days. Mean daily step count, light-intensity PA, moderate- to vigorous- intensity PA (MVPA), and SB were calculated. Objective walkability was measured by the 7-component Dutch Walkability Index within 500 m Euclidean buffers around residential addresses of participants. Subjective walkability was obtained from the Abbreviated Neighborhood Environment Walkability Scale. Linear regression models analyzed the associations of walkability with PA and SB, controlling for potential confounders. Objective walkability was negatively associated with light intensity PA in the most walkable quartile (b = -14.58, 95% CI = -20.94, -8.23). Compared to participants living in the least walkable neighborhoods, those in the most walkable quartile had statistically significantly higher SB levels (b = 11.64, 95% CI = 4.95, 18.32). For subjective walkability, mean daily step count was significantly higher in the most walkable quartile (b = 509.60, 95% CI = 243.38, 775.81). Higher subjective walkability was positively associated with MVPA (b = 4.40, 95% CI = 2.56, 6.23). Living in a neighborhood with higher objective walkability was associated with lower levels of PA and higher SB levels while higher subjective walkability was associated with higher levels of PA. These results show discordant findings and thus, the effect of walkability on participant PA and SB within our sample is to be determined.

The association of SARS-CoV-2 infection and tuberculosis disease with unfavorable treatment outcomes: A systematic review.

Whether SARS-CoV-2 infection and its management influence tuberculosis (TB) treatment outcomes is uncertain. We synthesized evidence on the association of SARS-CoV-2 coinfection (Coinfection Review) and its management (Clinical Management Review) on treatment outcomes among people with tuberculosis (TB) disease. We systematically searched the literature from 1 January 2020 to 6 February 2022. Primary outcomes included: unfavorable (death, treatment failure, loss-to-follow-up) TB treatment outcomes (Coinfection and Clinical Management Review) and/or severe or critical COVID-19 or death (Clinical Management Review). Study quality was assessed with an adapted Newcastle Ottawa Scale. Data were heterogeneous and a narrative review was performed. An updated search was performed on April 3, 2023. From 9,529 records, we included 11 studies and 7305 unique participants. No study reported data relevant to our review in their primary publication and data had to be contributed by study authors after contact. Evidence from all studies was low quality. Eight studies of 5749 persons treated for TB (286 [5%] with SARS-CoV-2) were included in the Coinfection Review. Across five studies reporting our primary outcome, there was no significant association between SARS-CoV-2 coinfection and unfavorable TB treatment outcomes. Four studies of 1572 TB patients-of whom 291 (19%) received corticosteroids or other immunomodulating treatment-were included in the Clinical Management Review, and two addressed a primary outcome. Studies were likely confounded by indication and discordant findings existed among studies. When updating our search, we still did not identify any study reporting data relevant to this review in their primary publication. No study was designed to answer our research questions of interest. It remains unclear whether TB/SARS-CoV-2 and its therapeutic management are associated with unfavorable outcomes. Research is needed to improve our understanding of risk and optimal management of persons with TB and SARS-CoV-2 infection. Registration: PROSPERO (CRD42022309818).

Consistency between Treatment Effects on Clinical and Brain Atrophy Outcomes in Alzheimer’s Disease Trials

BackgroundLongitudinal changes in volumetric MRI outcome measures have been shown to correlate well with longitudinal changes in clinical instruments and have been widely used as biomarker outcomes in clinical trials for Alzheimer’s disease (AD). While instances of discordant findings have been noted in some trials, especially the recent amyloid-removing therapies, the overall relationship between treatment effects on brain atrophy and clinical outcomes, and how it might depend on treatment target or mechanism, clinical instrument or imaging variable is not yet clear.ObjectiveTo systematically assess the consistency and therapeutic class-dependence of treatment effects on clinical outcomes and on brain atrophy in published reports of clinical trials conducted in mild cognitive impairment (MCI) and/or AD.DesignQuantitative review of the published literature. The consistency of treatment effects on clinical and brain atrophy outcomes was assessed in terms of statistical agreement with hypothesized equal magnitude effects (e.g., 30% slowing of both) and nominal directional concordance, as a function of therapeutic class.SettingInterventional randomized clinical trials.ParticipantsMCI or AD trial participants.InterventionTreatments included were those that involved ingestion or injection of a putatively active substance into the body, encompassing both pharmacological and controlled dietary interventions.MeasurementsEach trial included in the analysis reported at least one of the required clinical outcomes (ADAS-Cog, CDR-SB or MMSE) and at least one of the required imaging outcomes (whole brain, ventricular or hippocampal volume).ResultsData from 35 trials, comprising 185 pairwise comparisons, were included. Overall, the 95% confidence bounds overlapped with the line of identity for 150/185 (81%) of the imaging-clinical variable pairs. The greatest proportion of outliers was found in trials of anti-amyloid antibodies that have been shown to dramatically reduce the level of PET-detectable amyloid plaques, for which only 13/33 (39%) of observations overlapped the identity line. A Deming regression calculated using all data points yielded a slope of 0.54, whereas if data points from the amyloid remover class were excluded, the Deming regression line had a slope of 0.92. Directional discordance of treatment effects was also most pronounced for the amyloid-removing class, and for comparisons involving ventricular volume.ConclusionOur results provide a frame of reference for the interpretation of clinical and brain atrophy results from future clinical trials and highlight the importance of mechanism of action in the interpretation of imaging results.

Whole-body MRI in children and adolescents: Can T2-weighted Dixon fat-only images replace standard T1-weighted images in the assessment of bone marrow?

ObjectiveWhen performing whole-body MRI for bone marrow assessment in children, optimizing scan time is crucial.The aim was to compare T2 Dixon fat-only and TSE T1-weighted sequences in the assessment of bone marrow high signal areas seen on T2 Dixon water-only in healthy children and adolescents. Materials and methodsWhole-body MRIs from 196 healthy children and adolescents aged 6 to 19 years (mean 12.0) were obtained including T2 TSE Dixon and T1 TSE-weighted images. Areas with increased signal on T2 Dixon water-only images were scored using a novel, validated scoring system and classified into “minor” or “major” findings according to size and intensity, where “major” referred to changes easily being misdiagnosed as pathology in a clinical setting. Areas were assessed for low signal on T2 Dixon fat-only images and, after at least three weeks to avoid recall bias, on the T1-weighted sequence by two experienced pediatric radiologists. Results1250 high signal areas were evaluated on T2 Dixon water-only images. In 1159/1250 (92.7%) low signal was seen on both T2 Dixon fat-only and T1-weighted sequences while in 24 (1.9%) it was not present on either sequence, with an absolute agreement of 94.6%. Discordant findings were found in 67 areas, of which in 18 (1.5%) low signal was visible on T1-weighted images alone and in 49 (3.9%) on T2 Dixon fat-only alone. The overall kappa value between the two sequences was 0.39. The agreement was higher for major as compared to minor findings (kappa values of 0.69 and 0.29, respectively) and higher for the older age groups. ConclusionT2 Dixon fat-only can replace T1-weighted sequence on whole-body MRI for bone marrow assessment in children over the age of nine, thus reducing scan time.

Absolute and Relative Risks of Kidney Outcomes Associated With Lithium vs Valproate Use in Sweden

Among patients with bipolar disorder, discordant findings have been published on the nephrotoxic effects of lithium therapy. To quantify absolute and relative risks of chronic kidney disease (CKD) progression and acute kidney injury (AKI) in people who initiated lithium compared with valproate therapy and to investigate the association between cumulative use and elevated lithium levels and kidney outcomes. This cohort study had a new-user active-comparator design and used inverse probability of treatment weights to minimize confounding. Included patients initiated therapy with lithium or valproate from January 1, 2007, to December 31, 2018, and had a median follow-up of 4.5 years (IQR, 1.9-8.0 years). Data analysis began in September 2021, using routine health care data from the period 2006 to 2019 from the Stockholm Creatinine Measurements project, a recurrent health care use cohort of all adult residents in Stockholm, Sweden. New use of lithium vs new use of valproate and high (>1.0 mmol/L) vs low serum lithium levels. Progression of CKD (composite of >30% decrease relative to baseline estimated glomerular filtration rate [eGFR] and kidney failure), AKI (by diagnosis or transient creatinine elevations), new albuminuria, and annual eGFR decrease. Outcomes by attained lithium levels were also compared in lithium users. The study included 10 946 people (median [IQR] age, 45 [32-59] years; 6227 female [56.9%]), of whom 5308 initiated lithium therapy and 5638 valproate therapy. During follow-up, 421 CKD progression events and 770 AKI events were identified. Compared with patients who received valproate, those who received lithium did not have increased risk of CKD (hazard ratio [HR], 1.11 [95% CI, 0.86-1.45]) or AKI (HR, 0.88 [95% CI, 0.70-1.10]). Absolute 10-year CKD risks were low and similar: 8.4% in the lithium group and 8.2% in the valproate group. No difference in the risk of developing albuminuria or the annual rate of eGFR decrease was found between groups. Among more than 35 000 routine lithium tests, only 3% of results were in the toxic range (>1.0 mmol/L). Lithium values greater than 1.0 mmol/L, compared with lithium values of 1.0 mmol/L or less, were associated with increased risk of CKD progression (HR, 2.86; 95% CI, 0.97-8.45) and AKI (HR, 3.51; 95% CI, 1.41-8.76). In this cohort study, compared with new use of valproate, new use of lithium was meaningfully associated with adverse kidney outcomes, with low absolute risks that did not differ between therapies. However, elevated serum lithium levels were associated with future kidney risks, particularly AKI, emphasizing the need for close monitoring and lithium dose adjustment.

Correlations of Estimated Serum Small Dense Low-Density Lipoprotein and Isoprostane with Metabolic Syndrome Criteria between Metabolic Syndrome and Non-Metabolic Syndrome Subjects in Selangor

Introduction: Metabolic syndrome (MetS) is a global healthcare burden associated with increased risk of atherosclerosis (ATH). The relationship between atherogenic lipoprotein and oxidative stress biomarkers with clinical risk factors of MetS have not been fully explored. Therefore, the objective of this study is to determine the correlation between small dense low-density lipoprotein (sdLDL-c) and isoprostane (ISP) with MetS criteria and comparing these biomarkers between MetS and non-MetS. Materials and Methods: This was a cross sectional study involving 67 MetS and 43 non-MetS diagnosed by JIS criteria 2009. Demographic details and anthropometric measurements were recorded. Blood samples were collected to analyse serum plasma glucose, direct LDL, calculated sdLDL-c and ISP. Results: Mean serum sdLDL-c and ISP levels were significantly higher among those with MetS compared to non-MetS (1.14+0.44 mmol/L vs 0.87±0.38 mmol/L respectively, p=0.005). Similarly, mean serum ISP concentration was higher among MetS compared to non-MetS (884.40+602.69 ng/L vs 657.89±616.42 ng/L respectively, p= 0.054). sdLDL-c was positively correlated with TG in the MetS (Pearson correlation 0.501, p&lt;.001) whilst HDL-c was positively correlated with sdLDL-c among the non-MetS (Pearson Correlation 0.422, p&lt;.005). Conclusion: This study highlights the correlation between sdLDL-c and TG in among MetS, emphasizing the need to closely monitor and manage TG among this cohort to reduce the risk of ATH. It was also noted that HDL-c showed positive correlation with sdLDL-c among non-MetS. This discordant finding suggests that HDL-c itself may not be causally associated with cardiovascular benefits and that perhaps HDL-c subfractions may be a better approach to determine cardioprotective effects of HDL-c.