Diagnostic Score Research Articles

Predicting Alzheimer's Disease Progression Using a Versatile Sequence-Length-Adaptive Encoder-Decoder LSTM Architecture.

Detecting Alzheimer's disease (AD) accurately at an early stage is critical for planning and implementing disease-modifying treatments that can help prevent the progression to severe stages of the disease. In the existing literature, diagnostic test scores and clinical status have been provided for specific time points, and predicting the disease progression poses a significant challenge. However, few studies focus on longitudinal data to build deep-learning models for AD detection. These models are not stable to be relied upon in real medical settings due to a lack of adaptive training and testing. We aim to predict the individual's diagnostic status for the next six years in an adaptive manner where prediction performance improves with the number of patient visits. This study presents a Sequence-Length Adaptive Encoder-Decoder Long Short-Term Memory (SLA-ED LSTM) deep-learning model on longitudinal data obtained from the Alzheimer's Disease Neuroimaging Initiative archive. In the suggested approach, decoder LSTM dynamically adjusts to accommodate variations in training sequence length and inference length rather than being constrained to a fixed length. We evaluated the model performance for various sequence lengths and found that for inference length one, sequence length nine gives the highest average test accuracy and area under the receiver operating characteristic curves of 0.920 and 0.982, respectively. This insight suggests that data from nine visits effectively captures meaningful cognitive status changes and is adequate for accurate model training. We conducted a comparative analysis of the proposed model against state-of-the-art methods, revealing a significant improvement in disease progression prediction over the previous methods.

Poster 271: Improving Non-Invasive Diagnosis and Grading of Cartilage Defects in the Knee - Accuracy of Ultra High Field 7-Tesla MRI as Compared with Arthroscopy

Objectives: Osteoarthritis (OA) is a joint disease characterized by degradation of articular cartilage and subchondral bone. Cartilage injury plays an important role in the pathogenesis of osteoarthritis, and disease modifying treatments aiming to preserve and possibly regenerate cartilage are an area of active interest. Early diagnosis is crucial, as the disease may be more responsive to treatment at an early stage, and there is a critical unmet need for improved non-invasive morphologic cartilage imaging techniques. Standard clinical MRI is performed on a 1.5T or 3T machine. Ultra-high field (UHF) 7-Tesla (7T) magnetic resonance imaging (MRI) is a new technology that offers 2.3x improved signal-to noise ratio (SNR) compared to 3T MRI and 2.8x SNR compared to 1.5T MRI. The purpose of this study was to estimate the accuracy of 7T MRI for the detection and grading of cartilage lesions in the knee. The hypothesis was that 7T images would offer better detection and more accurate grading of chondral lesions than standard clinical grade MRI scans. Methods: In this prospective, paired, blinded study, patients who had undergone a 1.5 or 3T standard of care (SOC) MRI and were scheduled for knee arthroscopy were enrolled (10/2019 to 08/2021) and a study intervention 7T MRI was performed prior to surgery. The study was approved by our institutional review board, and it was funded by the Methodist-Siemens Collaboration. Exclusion criteria included contraindication to MRI (e.g., pacemaker), weight less than 30 kg, and pregnancy. Scans were reviewed by three independent fellowship-trained radiologists who were blinded to clinical and arthroscopic data. Scans were reviewed over 5 days, with a 4 week “washout” period between review of SOC and 7T scans to limit recall bias. Readers were blinded to clinical and arthroscopic data and graded all six articular surfaces of the knee (patella, trochlea, lateral condyle, medial condyle, lateral tibia, medial tibia) using a modified Outerbridge classification system. At the time of arthroscopy, each articular surface was graded by the operating surgeon according to a modified Outerbridge system similar to above, with the exception that Grade 1 = softening of the articular cartilage. The surgeon was blinded to 7T images at the time of arthroscopy, although they had access to the SOC MRI, which was necessary for patient care. Using arthroscopy as the gold standard, we calculated sensitivity and specificity of SOC MRI and 7T MRI. An Outerbridge grade of 0 was classified as negative, while a grade of 1-4 was classified as positive. A secondary analysis of sensitivity and specificity was performed on a per articular surface basis, with 6 articular surfaces per patient after correction for within subject clustered data. A Mann-Whitney U test was used to compare diagnostic scores and ratings between instruments (SOC vs. 7T). Coefficients of variation between observers within each instrument were compared for each variable using a paired sample t-test. Type-I error was set at alpha=0.05 Results: A total of 100 patients (age: 43 ± 14, 54 female, 46 male) were enrolled. 7T MRI resulted in improved sharpness (defined by visibility of nerve fascicles) and shading (based on artifacts) compared to SOC MRI (Figure 1, p < 0.001 for both). There was improved contrast between fluid and cartilage with 7T MRI (using confidence rating at axial mid-patella, p = 0.003). 7T MRI had a higher sensitivity in detecting cartilage lesions for five of the six articular surfaces when using the arthroscopic gold standard, but with lower specificity for all surfaces (Figure 2). Finally, there was improved inter-observer reliability in detecting and grading cartilage defects with 7T compared to SOC MRI (p < 0.05). Conclusion: Based on our findings thus far, 7T MRI appears to result in improved measurement ratings, sensitivity, and inter-observer reliability compared to SOC in detecting cartilage lesions in the knee. Further work is needed to evaluate cost effectiveness of 7T MRI.

Clinical Tools for Optimizing Therapeutic Decision-Making in Prostate Cancer: A Five-Year Retrospective Analysis.

The effective staging of prostate cancer is essential for optimizing treatment and predicting outcomes. This study assessed the correlation between detailed preoperative diagnostic scores and postoperative outcomes to evaluate the accuracy of cancer restaging and its impact on treatment decisions and prognosis after prostatectomy. This retrospective study analyzed 133 prostate cancer patients who underwent prostatectomies at "Pius Brinzeu" Clinical Emergency Hospital in Timisoara over five years. Preoperative Gleason scores increased significantly across risk categories, from an average of 6.21 in low-risk patients to 7.57 in high-risk patients. This trend continued postoperatively, with scores rising from 7.04 to 8.33, respectively. The average increase in Gleason scores from preoperative to postoperative assessments was most pronounced in high-risk patients, at 0.76. Significant changes in clinical staging included increases in NCCN risk, where high-risk patients showed a 30% increase, and ISUP grade, with a 26.7% increase in the high-risk category. Notably, nodal status changes were also significant in high-risk patients, showing a 23.3% increase. The incidence of MRI-detected adenopathy was notably higher in the high-risk group (50%). Furthermore, there were significant correlations between the preoperative CAPRA score and postoperative ISUP grade (r = 0.261) and the preoperative PIRADS score and postoperative ISUP grade (r = 0.306). Similar observations were made between the preoperative and postoperative Gleason scores (r = 0.286) and the number of positive fragments (r = 0.227) with the postoperative ISUP grading. Furthermore, the preoperative CAPRA score was significantly correlated (r = 0.261) with the postoperative ISUP grading. Preoperative MRI findings, which included assessments of adenopathy and seminal vesicle invasion, were also significantly correlated (r = 0.218) with the postoperative pathological findings. Additionally, a significant correlation was found between the preoperative PIRADS score and postoperative ISUP grade (r = 0.306). In forecasting the aggressiveness and staging of prostate cancer following surgery, preoperative PSA levels showed an AUC of 0.631; the preoperative Gleason score had an AUC adjusted to 0.582, and the number of positive biopsy fragments indicated an AUC of 0.566. These results highlight the necessity of accurate and comprehensive preoperative assessments to better predict disease progression and refine treatment strategies.

Heart failure with preserved ejection fraction management: a systematic review of clinical practice guidelines and recommendations.

Multiple guidelines exist for the diagnosis and management of heart failure with preserved ejection fraction (HFpEF). We systematically reviewed current guidelines and recommendations, developed by national and international medical organizations, on the management of HFpEF in adults to aid clinical decision-making. We searched MEDLINE and EMBASE on 28 February 2024 for publications over the last 10 years as well as websites of organizations relevant to guideline development. Of the ten guidelines and recommendations retrieved, seven showed considerable rigour of development and were subsequently retained for analysis. There was consensus on the definition of HFpEF and the diagnostic role of serum natriuretic peptides and resting transthoracic echocardiography. Discrepancies were identified in the thresholds of serum natriuretic peptides and transthoracic echocardiography parameters used to diagnose HFpEF. There was agreement on the general pharmacological and supportive management of acute and chronic HFpEF. However, differences exist in strategies to identify and address specific phenotypes. Contemporary guidelines for HFpEF management agree on measures to avoid its development and the consideration of cardiac transplantation in advanced disease. There were discrepancies in recommended frequency of surveillance for patients with HFpEF and sparse recommendations on screening for HFpEF in the general population, use of diagnostic scoring systems, and the role of newly emerging therapies.

The Diagnostic Efficiency and Safety of Transbronchial Lung Cryobiopsy Using 1.1-mm Cryoprobe in Diagnosing Interstitial Lung Disease.

Transbronchial lung cryobiopsy (TBLC) is increasingly used to diagnose interstitial lung disease (ILD). The 1.1-mm cryoprobe has recently been available in clinical practice. The diagnostic yield and safety of TBLC using a 1.1-mm cryoprobe need to be confirmed. A prospective, randomized controlled trial was conducted in patients with suspected ILD and randomly assigned to 1.1-mm and 1.9-mm cryoprobe groups. The primary outcome was the diagnostic yield of multidisciplinary discussion. Secondary outcomes were sample quality and incidence of complications. The tension and stress effects during TBLC onto the target lobe caused by 1.1-mm and 1.9-mm cryoprobes were also evaluated using finite element analysis. A total of 224 patients were enrolled. No significant differences were observed in the diagnostic yield (80.4% vs. 79.5%, p = 0.845) and sample quality scores (5.73 ± 0.64 vs. 5.66 ± 0.77; p = 0.324) between the 1.9-mm cryoprobe group and 1.1-mm cryoprobe group. The average surface areas of samples in 1.1-mm cryoprobe group were smaller, while no difference in sample weights was observed. A decreased incidence of moderate bleeding was found in the 1.1-mm cryoprobe group (17.0% vs. 6.2%, p = 0.027), while there was no difference in the incidence of the pneumothorax, there was a trend to higher rate of pneumothorax in 1.1-mm group. In finite element analysis, the 1.1-mm cryoprobe required the largest tension and produced the largest stress. Compared with a 1.9-mm cryoprobe, there was no difference in specimen quality or diagnostic rate but smaller sample size with a 1.1-mm cryoprobe. There was a decreased risk of moderate bleeding, but a trend towards increased risk for pneumothorax with 1.1-mm cryoprobe. Clinicaltrials.gov identifier NCT04047667; registered August 4, 2019.

Assessment of metabolomic variations among individuals returning to plain areas after exposure to high altitudes: a metabolomic analysis of human plasma samples with high-altitude de-acclimatization syndrome.

High altitude de-acclimatization (HADA) is gradually becoming a public health concern as millions of individuals of different occupations migrate to high-altitude areas for work due to economic growth in plateau areas. HADA affects people who return to lower elevations after exposure to high altitudes. It causes significant physiological and functional changes that can negatively impact health and even endanger life. However, uncertainties persist about the detailed mechanisms underlying HADA. We established a population cohort of individuals with HADA and assessed variations in metabolite composition. Plasm samples of four groups, including subjects staying at plain (P) and high altitude (H) as well as subjects suffering from HADA syndrome with almost no reaction (r3) and mild-to-moderate reaction (R3) after returning to plain from high altitude, were collected and analyzed by Liquid Chromatography-Mass Spectrometry metabolomic. Multivariate statistical analyses were used to explore significant differences and potential clinical prospect of metabolites. Although significantly different on current HADAS diagnostic symptom score, there were no differences in 17 usual clinical indices between r3 and R3. Further multivariate analyses showed isolated clustering distribution of the metabolites among the four groups, suggesting significant differences in their metabolic characteristics. Through K-means clustering analysis, we identified 235 metabolites that exhibited patterns of abundance change consistent with phenotype of HADA syndrome. Pathway enrichment analysis indicated a high influence of polyunsaturated fatty acids under high-altitude conditions. We compared the metabolites between R3 and r3 and found 107 metabolites with differential abundance involved in lipid metabolism and oxidation, suggesting their potential role in the regulation of oxidative stress homeostasis. Among them, four metabolites might play a key role in the occurrence of HADA, including 11-beta-hydroxyandrosterone-3-glucuronide, 5-methoxyindoleacetate, 9,10-epoxyoctadecenoic acid, and PysoPC (20:5). We observed the dynamic variation in the metabolic process of HADA. Levels of four metabolites, which might be provoking HADA mediated through lipid metabolism and oxidation, were expected to be explore prospective indices for HADA. Additionally, metabolomics was more efficient in identifying environmental risk factors than clinical examination when dramatic metabolic disturbances underlying the difference in symptoms were detected, providing new insights into the molecular mechanisms of HADAS.

The impact of orbital floor defect ratio on changes in the inferior rectus muscle and prediction of posttraumatic enophthalmos – A cadaver study

BackgroundOrbital floor fractures result in critical changes in the shape and inferior rectus muscle (IRM) position. Radiological imaging of IRM changes can be used for surgical decision making or prediction of ocular symptoms. Studies with a systematic consideration of the orbital floor defect ratio in this context are missing in the literature. Accordingly, this study on human cadavers aimed to systematically investigate the impact of the orbital floor defect ratio on changes in the IRM and the prediction of posttraumatic enophthalmos. MethodsSeventy-two orbital floor defects were placed in cadaver specimens using piezosurgical removal. The orbital defect area (ODA), orbital floor area (OFA), position and IRM shape, and enophthalmos were measured using computed tomography (CT) scans. ResultsThe ODA/OFA ratio correlated significantly (p < 0.001) with the shape (Spearman’s rho: 0.558) and position (Spearman’s rho: 0.511) of the IRM, and with enophthalmos (Spearman’s rho: 0.673). Increases in the ODA/OFA ratio significantly rounded the shape of the IRM (ß: 0.667; p < 0.001) and made a lower position of the IRM more likely (OR: 1.093; p = 0.003). In addition, increases in the ODA/OFA ratio were significantly associated with the development of relevant enophthalmos (OR: 1.159; p = 0.008), adjusted for the defect localization and shape of the IRM. According to receiver operating characteristics analysis (AUC: 0.876; p < 0.001), a threshold of ODA/OFA ratio ≥ 32.691 for prediction of the risk of development of enophthalmos yielded a sensitivity of 0.809 and a specificity of 0.842. ConclusionThe ODA/OFA ratio is a relevant parameter in the radiological evaluation of orbital floor fractures, as it increases the risk of relevant enophthalmos, regardless of fracture localization and shape of the IRM. Therefore, changes in the shape and position of the IRM should be considered in surgical treatment planning. A better understanding of the correlates of isolated orbital floor fractures may help to develop diagnostic scores and standardize therapeutic algorithms in the future.

Screening Options in Autism Telediagnosis: Examination of TAP, M-CHAT-R, and DCI Concordance and Predictive Value in a Telediagnostic Model.

Tele-assessment of autism in early childhood has increased. However, it is unclear how autism screening tools (M-CHAT-R, DCI) function as part of tele-assessment and relate to a commonly used tele-assessment instrument, the TAP. 361 families from a clinically referred sample of children (mean age: 27.63 months, sd = 4.86 months) completed the M-CHAT-R and DCI prior to a tele-assessment visit utilizing the TAP. Data was collected on demographic background, measure scores, and diagnostic outcome. No significant differences in measure scores or diagnostic findings emerged in age at referral, age group, age at diagnosis, or child sex, ethnicity, or racial background. The M-CHAT-R and DCI correlated strongly and positively. Older age was associated with lower risk scores on screening instruments. Children with autism had significantly higher scores on all screener and subdomain scores, with the exception of DCI Behavior. Subdomains of the DCI emerged as the strongest predictor of diagnostic outcome. Both the DCI total score and the M-CHAT-R significantly related to diagnostic outcome and TAP score in this tele-assessment model, regardless of child age or sex. Findings also support use of the DCI for children under 24 months of age.

Utility and Validity of the HFA-PEFF andH2FPEF Scores in Patients With Symptomatic Atrial Fibrillation.

Diagnosis of heart failure with preserved ejection fraction (HFpEF) in patients with atrial fibrillation (AF) represents a significant clinical challenge. Two diagnostic scoring tools have been developed to aid the noninvasive diagnosis of HFpEF: the HFA-PEFF (Heart Failure Association Pre-test assessment, Echocardiography and natriuretic peptide, Functional testing, Final etiology) and the H2FPEF scoring systems. The purpose of this study was to evaluate the performance of these 2 scoring tools for the diagnosis of HFpEF against a gold standard of invasive evaluation in a cohort of patients with AF. The authors recruited consecutive patients with symptomatic AF and preserved ejection fraction who were scheduled for an AF ablation procedure. Gold-standard invasive diagnosis of HFpEF was performed at the AF ablation procedure using mean left atrial pressure at rest and following infusion of 500mL fluid. Each participant was scored according to the noninvasive HFA-PEFF and H2FPEF scoring systems. Sensitivity and specificity analyses were performed to assess the accuracy of these scoring systems in diagnosing HFpEF. In total, 120 participants were recruited. HFpEF was diagnosed invasively in 88 (73.3%) participants, whereas 32 (26.7%) had no HFpEF. Using the HFA-PEFF score, 38 (31.7%) participants had a high probability of HFpEF and 82(68.3%) had low/intermediate probability of HFpEF. Using the H2FPEF tool, 72 (60%) participants had a high probability of HFpEF and 48 (40%) had intermediate probability. A high HFA-PEFF (≥5 points) score could diagnose HFpEF with a sensitivity of 40% and a specificity of 91%, and a high H2FPEF score (≥6 points) could diagnose HFpEFwith a sensitivity of 69% and specificity of 66%. Overall diagnostic accuracy was similar using both tools (AUC:0.663 vs 0.707, respectively; P = 0.636). Against a gold standard of invasively diagnosed HFpEF, the HFA-PEFF and H2FPEF scores demonstrate only moderate accuracy in patients with AF and should be utilized with caution in this cohort of patients. (Characterising Left Atrial Function and Compliance in Atrial Fibrillation; ACTRN12620000639921).

Virtual Remote Pathology Education in Support of Virtual Remote Gynecologic-Oncology Training: The Open Pathology Education Network Pilot Proof of Concept Experience.

The subspecialty workforce in pathology globally is inadequate for the demands of many modern therapies. The Open Pathology Education Network (OPEN) was formed to augment the global pathology workforce. The International Gynecologic Cancer Society (IGCS) virtual gynecologic-oncology (gyn-onc) fellowship training identified needs for higher-level pathology support. To report on an OPEN-IGCS pilot project to support gyn-onc and pathology education efforts in a developing country. Curriculum with learning objectives and content from open sources was assembled. Mentoring sessions included bidirectional case sharing. Trainees received sequential curricula assignments and had options for communication outside mentoring sessions. Pretest and posttest digital slide assessments were included. Mentors attended the gynecology tumor board, allowing for the assessment of quality and accuracy of pathology diagnosis for cases discussed. Learners completing the pretest and posttest showed substantial improvement, with 2 practicing pathologists improving their diagnostic scores from 60% to an average of 95%. A third trainee-level participant also improved, but to a lesser degree. Qualitative assessments included increased confidence in presentation and an increased ability to anticipate questions, raise issues of expanded differential diagnoses, and articulate appropriate workup. Observations of clinicians who participated also noted increased confidence in participating pathologists. Secondary value included establishing an expanded network of support in other subspecialties for participants. Pathologic issues at the tumor board decreased, from more than 50% in the first 3 months of study to 0% in the last 3 months of study. The curriculum was embedded into a self-paced learning portal at courses.open-pathology.org. The OPEN-IGCS collaboration model shows the potential to provide subspecialty pathology training remotely.

Direct abdominal vein thrombus imaging (DATI): a contrast-free black-blood MR technique for the diagnosis of abdominal vein thrombosis.

To develop and evaluate a direct abdominal vein thrombus imaging (DATI) technique, based on a respiratory navigating SPACE sequence with DANTE black-blood preparation, for diagnosing abdominal vein thrombosis (AVT) without the use of exogenous contrast agents. We prospectively enrolled 10 healthy subjects and 28 suspected AVT patients who underwentDATI scans on 3.0T MRI. Contrast-enhanced CT venography (CTV) was also conducted on the suspected AVT patients for comparison. All images were analyzed by two blinded radiologists who independently evaluated randomized images and gave image quality and diagnostic confidence scores (1-poor, 4-excellent) for DATI and CTV. The accuracy (ACC), sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) of CTV were calculated using CTV as a standard reference. The diagnostic agreement between DATI and CTV as well as the interobserver agreement were conducted using Cohen κ test. The patient study demonstrated that DATI can provide adequate thrombus signal intensity and the contrast between the thrombus to dark venous lumen for the diagnosis of AVT. It offers good to excellent image quality (reader1/reader2: 3.50 ± 0.64/3.42 ± 0.63, κ = 0.872) and diagnostic confidence (reader1/reader2: 3.71 ± 0.53/3.78 ± 0.42, κ = 0.804) for the diagnosis of AVT. Taking CTV as a reference, DATI has high accuracy (96.6%), SE (91.5%), SP (98.0%), PPV (92.3%), and NPV (97.8%). DATI can provide good to excellent image quality, effective venous blood signal suppression, and definitive thrombus detection for the diagnosis of AVT without the use of exogenous contrast agents.

Early identification of macrophage activation syndrome secondary to systemic lupus erythematosus with machine learning

ObjectiveThe macrophage activation syndrome (MAS) secondary to systemic lupus erythematosus (SLE) is a severe and life-threatening complication. Early diagnosis of MAS is particularly challenging. In this study, machine learning models and diagnostic scoring card were developed to aid in clinical decision-making using clinical characteristics.MethodsWe retrospectively collected clinical data from 188 patients with either SLE or the MAS secondary to SLE. 13 significant clinical predictor variables were filtered out using the Least Absolute Shrinkage and Selection Operator (LASSO). These variables were subsequently utilized as inputs in five machine learning models. The performance of the models was evaluated using the area under the receiver operating characteristic curve (ROC-AUC), F1 score, and F2 score. To enhance clinical usability, we developed a diagnostic scoring card based on logistic regression (LR) analysis and Chi-Square binning, establishing probability thresholds and stratification for the card. Additionally, this study collected data from four other domestic hospitals for external validation.ResultsAmong all the machine learning models, the LR model demonstrates the highest level of performance in internal validation, achieving a ROC-AUC of 0.998, an F1 score of 0.96, and an F2 score of 0.952. The score card we constructed identifies the probability threshold at a score of 49, achieving a ROC-AUC of 0.994 and an F2 score of 0.936. The score results were categorized into five groups based on diagnostic probability: extremely low (below 5%), low (5–25%), normal (25–75%), high (75–95%), and extremely high (above 95%). During external validation, the performance evaluation revealed that the Support Vector Machine (SVM) model outperformed other models with an AUC value of 0.947, and the scorecard model has an AUC of 0.915. Additionally, we have established an online assessment system for early identification of MAS secondary to SLE.ConclusionMachine learning models can significantly improve the diagnostic accuracy of MAS secondary to SLE, and the diagnostic scorecard model can facilitate personalized probabilistic predictions of disease occurrence in clinical environments.

Uncovering Unrecognized Heart Failure With Preserved Ejection Fraction Among Individuals With Obesity and Dyspnea.

Although heart failure with preserved ejection fraction (HFpEF) has become the predominant heart failure subtype, it remains clinically under-recognized. HFpEF diagnosis is particularly challenging in the setting of obesity given the limitations of natriuretic peptides and resting echocardiography. We examined invasive and noninvasive HFpEF diagnostic criteria among individuals with obesity and dyspnea without known cardiovascular disease to determine the prevalence of hemodynamic HFpEF in the community. Research volunteers with dyspnea and obesity underwent resting echocardiography; participants with possible pulmonary hypertension qualified for invasive cardiopulmonary exercise testing. HFpEF was defined using rest or exercise pulmonary capillary wedge pressure criteria (≥15 mm Hg or Δpulmonary capillary wedge pressure/Δcardiac output slope, >2.0 mm Hg·L-1·min-1). Among n=78 participants (age, 53±13 years; 65% women; body mass index, 37.3±6.8 kg/m2), 40 (51%) met echocardiographic criteria to undergo invasive cardiopulmonary exercise testing. In total, 24 participants (60% among the cardiopulmonary exercise testing group, 31% among the total sample) were diagnosed with HFpEF by rest or exercise pulmonary capillary wedge pressure (n=12) or exercise criteria (n=12). There were no differences in NT-proBNP (N-terminal pro-B-type natriuretic peptide; 79 [62-104] versus 73 [57-121] pg/mL) or resting echocardiography (mitral E/e' ratio, 9.1±3.1 versus 8.0±2.7) among those with versus without HFpEF (P>0.05 for all). Distributions of HFpEF diagnostic scores were similar, with the majority classified as intermediate risk (100% versus 93.75% [H2FPEF] and 87.5% versus 68.75% [HFA-PEFF (Heart Failure Association Pretest assessment, echocardiography and natriuretic peptide, functional testing, and final etiology)] in those with versus without HFpEF). Among adults with obesity and dyspnea without known cardiovascular disease, at least a third had clinically unrecognized HFpEF uncovered on invasive cardiopulmonary exercise testing. Clinical, biomarker, resting echocardiography, and diagnostic scores were similar among those with and without HFpEF. These results suggest clinical underdiagnosis of HFpEF among individuals with obesity and dyspnea and highlight limitations of noninvasive testing in the identification of HFpEF.

Abstract 1087: Cardiovascular Risk Prediction By Platelet Transcriptomics

Background: Hyperreactive platelets are central to atherothrombotic events, including myocardial infarction (MI) and stroke. Currently, no routine clinical test can identify individuals with hyperreactive platelets. The development of a diagnostic platelet hyperreactivity test could identify patients most likely to benefit from antiplatelet therapy to reduce cardiovascular (CV) events. Aim: To develop a diagnostic tool to discriminate platelet hyperreactivity and CV risk. Methods: Platelet aggregation (0.4 μM epinephrine) was assessed by light transmission aggregometry (LTA) and responses &gt;60% were classified as “hyperreactive” and &lt;40% “normoreactive”. Simultaneously, platelet RNA was collected and sequenced (RNA-seq; n=88). Using machine-based learning, a hyperreactive platelet transcriptomic signature was identified, and a Platelet Reactivity ExpreSsion Score (PRESS) was assigned to each participant. Model training performance was evaluated by 10-fold cross-validation. Signature validation was performed in (a) control cohort without CV disease (n=35), and the diagnostic capacity of PRESS was assessed in patients (b) undergoing coronary angiography (n=28) and (c) lower extremity revascularization (LER, n=129). Results: PRESS successfully identified a hyperreactive platelet phenotype in patients with CV disease (AUC 0.81, 95% CI 0.68 - 0.94) and in an independent cohort of healthy participants off antiplatelet therapy (AUC 0.77, 95% CI 0.75 - 0.79). In patients undergoing diagnostic cardiac catheterization, PRESS was significantly higher in patients experiencing an acute MI (β=1.8, adj p=0.02). Among patients undergoing LER, those with a PRESS above the median were more likely to develop a future CV event (adj HR 1.90, CI 1.07 - 3.36, p=0.027). Conclusions: A platelet-derived transcriptomic signature identified individuals with hyperreactive platelets and was associated with increased CV risk. A diagnostic platelet reactivity score may facilitate a personalized approach to antithrombotic therapy for CV risk reduction.

Prognosis and Treatment of Gastric Cancer: A 2024 Update.

Due to the high death rate associated with gastric cancer, a great deal of research has been conducted on this disease. The goal of this paper was to start a trimestral review of 2024 for the year that had just started. The scientific literature from 1 January 2024 was chosen with consideration of the the guidelines of the European Society of Medical Oncology (ESMO), which are updated with new findings but not systematically reviewed annually. We used the search term "gastric cancer" to find the most current publications in the PubMed database related to the prognosis and treatment of gastric cancer. As previously said, the only articles that satisfied the inclusion criteria were those from 2024. Articles with case reports were eliminated since they had nothing to do with our research. The treatment of gastric cancer is the focus of the majority of articles from 2024. The primary research axes include surgery and immunonutrition, immunotherapy and Helicobacter pylori, and therapeutic targets. Patients with GC may experience less psychological, social, and financial hardship if the recently identified markers discovered in circulation are better assessed and validated. This could be achieved by either including the markers in an artificial intelligence-based diagnostic score or by using them in conjunction with traditional diagnostic methods. Due to the rising death rate associated with GC, funding for research into diagnosis, prognosis, therapy, and therapeutic targets is essential.

Design and Development of an Antigen Test for SARS-CoV-2 Nucleocapsid Protein to Validate the Viral Quality Assurance Panels.

The continuing mutability of the SARS-CoV-2 virus can result in failures of diagnostic assays. To address this, we describe a generalizable bioinformatics-to-biology pipeline developed for the calibration and quality assurance of inactivated SARS-CoV-2 variant panels provided to Radical Acceleration of Diagnostics programs (RADx)-radical program awardees. A heuristic genetic analysis based on variant-defining mutations demonstrated the lowest genetic variance in the Nucleocapsid protein (Np)-C-terminal domain (CTD) across all SARS-CoV-2 variants. We then employed the Shannon entropy method on (Np) sequences collected from the major variants, verifying the CTD with lower entropy (less prone to mutations) than other Np regions. Polyclonal and monoclonal antibodies were raised against this target CTD antigen and used to develop an Enzyme-linked immunoassay (ELISA) test for SARS-CoV-2. Blinded Viral Quality Assurance (VQA) panels comprised of UV-inactivated SARS-CoV-2 variants (XBB.1.5, BF.7, BA.1, B.1.617.2, and WA1) and distractor respiratory viruses (CoV 229E, CoV OC43, RSV A2, RSV B, IAV H1N1, and IBV) were assembled by the RADx-rad Diagnostics core and tested using the ELISA described here. The assay tested positive for all variants with high sensitivity (limit of detection: 1.72-8.78 ng/mL) and negative for the distractor virus panel. Epitope mapping for the monoclonal antibodies identified a 20 amino acid antigenic peptide on the Np-CTD that an in-silico program also predicted for the highest antigenicity. This work provides a template for a bioinformatics pipeline to select genetic regions with a low propensity for mutation (low Shannon entropy) to develop robust 'pan-variant' antigen-based assays for viruses prone to high mutational rates.

The Dual Lens of Endoscopy and Histology in the Diagnosis and Management of Eosinophilic Gastrointestinal Disorders-A Comprehensive Review.

Eosinophilic Gastrointestinal Disorders (EGIDs) are a group of conditions characterized by abnormal eosinophil accumulation in the gastrointestinal tract. Among these EGIDs, Eosinophilic Esophagitis (EoE) is the most well documented, while less is known about Eosinophilic Gastritis (EoG), Eosinophilic Enteritis (EoN), and Eosinophilic Colitis (EoC). The role of endoscopy in EGIDs is pivotal, with applications in diagnosis, disease monitoring, and therapeutic intervention. In EoE, the endoscopic reference score (EREFS) has been shown to be accurate in raising diagnostic suspicion and effective in monitoring therapeutic responses. Additionally, endoscopic dilation is the first-line treatment for esophageal strictures. For EoG and EoN, while the literature is more limited, common endoscopic findings include erythema, nodules, and ulcerations. Histology remains the gold standard for diagnosing EGIDs, as it quantifies eosinophilic infiltration. In recent years, there have been significant advancements in the histological understanding of EoE, leading to the development of diagnostic scores and the identification of specific microscopic features associated with the disease. However, for EoG, EoN, and EoC, precise eosinophil count thresholds for diagnosis have not yet been established. This review aims to elucidate the role of endoscopy and histology in the diagnosis and management of the three main EGIDs and to analyze their strengths and limitations, their interconnection, and future research directions.

Spectrum of ERCC6-Related Cockayne Syndrome (Type B): From Mild to Severe Forms.

(1) Background: Cockayne syndrome (CS) is an ultra-rare multisystem disorder, classically subdivided into three forms and characterized by a clinical spectrum without a clear genotype-phenotype correlation for both the two causative genes ERCC6 (CS type B) and ERCC8 (CS type A). We assessed this, presenting a series of patients with genetically confirmed CSB. (2) Materials and Methods: We retrospectively collected demographic, clinical, genetic, neuroimaging, and serum neurofilament light-chain (sNFL) data about CSB patients; diagnostic and severity scores were also determined. (3) Results: Data of eight ERCC6/CSB patients are presented. Four patients had CS I, three patients CS II, and one patient CS III. Various degrees of ataxia and spasticity were cardinal neurologic features, with variably combined systemic characteristics. Mean age at diagnosis was lower in the type II form, in which classic CS signs were more evident. Interestingly, sNFL determination appeared to reflect clinical classification. Two novel premature stop codon and one novel missense variants were identified. All CS I subjects harbored the p.Arg735Ter variant; the milder CS III subject carried the p.Leu764Ser missense change. (4) Conclusion: Our work confirms clinical variability also in the ERCC6/CSB type, where manifestations may range from severe involvement with prenatal or neonatal onset to normal psychomotor development followed by progressive ataxia. We propose, for the first time in CS, sNFL as a useful peripheral biomarker, with increased levels compared to currently available reference values and with the potential ability to reflect disease severity.

Simplified Criteria for Identification of Familial Hypercholesterolemia in Children: Application in Real Life.

The diagnosis of familial hypercholesterolemia (FH) in children is primarily based on main criteria including low-density lipoprotein cholesterol (LDL-C) levels, increased in the proband and relatives, and its inheritance. Two other relevant parameters are symptoms, rarely occurring in children, as rare are the FH homozygous patients, and the mutation detection of related genes. The latter allows the final diagnosis, although it is not commonly available. Moreover, the application of diagnostic scores, useful in adults, is poorly applied in children. The aim of this study was to compare the reliability of criteria here applied with different scores, apart from genetic analysis, for FH diagnosis. The latter was then confirmed by genetic analysis. n. 180 hypercholesterolemic children (age 10.2 ± 4.6 years) showing LDL-C levels ≥95th percentile (age- and sex-related), the dominant inheritance pattern of hypercholesterolemia (including LDL-C ≥95th percentile in one parent), were considered potentially affected by FH and included in the study. The molecular analysis of the LDLR, APOB and PCSK9 genes was applied to verify the diagnostic accuracy. Biochemical and family history data were also retrospectively categorized according to European Atherosclerosis Society (EAS), Simon Broome Register (SBR), Pediatric group of the Italian LIPIGEN (LIPIGEN-FH-PED) and Dutch Lipid Clinic Network (DLCN) criteria. Detailed kindred biochemical and clinical assessments were extended to three generations. The lipid profile was detected by standard laboratory kits, and gene analysis was performed by traditional sequencing or Next-Generation Sequencing (NGS). Among 180 hypercholesterolemic subjects, FH suspected based on the above criteria, 164/180 had the diagnosis confirmed, showing causative mutations. The mutation detection rate (MDR) was 91.1%. The scoring criteria proposed by the EAS, SBR and LIPIGEN-FH-PED (resulting in high probable, possible-defined and probable-defined, respectively) showed high sensitivity (~90%), low specificity (~6%) and high MDR (~91%). It is noteworthy that their application, as a discriminant for the execution of the molecular investigation, would lead to a loss of 9.1%, 9.8% and 9.1%, respectively, of FH-affected patients, as confirmed by the genetic analysis. DLCN criteria, for which LDL-C cut-offs are not specific for childhood, would lead to a loss of 53% of patients with mutations. In the pediatric population, the combination of LDL-C ≥95th percentile in the proband and the dominant inheritance pattern of hypercholesterolemia, with LDL-C ≥95th percentile in one parent, is a simple, useful and effective diagnostic criterion, showing high MDR. This pattern is crucial for early FH diagnosis. EAS, SBR and LIPIGEN-FH-PED criteria can underestimate the real number of patients with gene mutations and cannot be considered strictly discriminant for the execution of molecular analysis.

Prediction of tumor origin in cancers of unknown primary origin with cytology-based deep learning.

Cancer of unknown primary (CUP) site poses diagnostic challenges due to its elusive nature. Many cases of CUP manifest as pleural and peritoneal serous effusions. Leveraging cytological images from 57,220 cases at four tertiary hospitals, we developed a deep-learning method for tumor origin differentiation using cytological histology (TORCH) that can identify malignancy and predict tumor origin in both hydrothorax and ascites. We examined its performance on three internal (n = 12,799) and two external (n = 14,538) testing sets. In both internal and external testing sets, TORCH achieved area under the receiver operating curve values ranging from 0.953 to 0.991 for cancer diagnosis and 0.953 to 0.979 for tumor origin localization. TORCH accurately predicted primary tumor origins, with a top-1 accuracy of 82.6% and top-3 accuracy of 98.9%. Compared with results derived from pathologists, TORCH showed better prediction efficacy (1.677 versus 1.265, P < 0.001), enhancing junior pathologists' diagnostic scores significantly (1.326 versus 1.101, P < 0.001). Patients with CUP whose initial treatment protocol was concordant with TORCH-predicted origins had better overall survival than those who were administrated discordant treatment (27 versus 17 months, P = 0.006). Our study underscores the potential of TORCH as a valuable ancillary tool in clinical practice, although further validation in randomized trials is warranted.