Diagnostic Utility Research Articles

ROS1 Translocation Detection in NSCLC: A Comparative Study of PGDx and FISH

Abstract In the United States, lung cancer is the leading cause of cancer-related deaths. In recent decades, the advent of molecularly-targeted therapies in the management of non-small-cell lung cancer (NSCLC) has led to significant improvements in patient outcomes. As such, optimum care depends on timely molecular testing. The mutational spectrum associated with NSCLC, however, is complex and riddled with various point mutations, amplifications, and rearrangements/fusions across multiple genes. Comprehensive testing of NSCLC has historically required multiple testing modalities to detect all clinically-relevant molecular targets. At our institution, a combination of immunohistochemistry, fluorescence in situ hybridization (FISH), and sequencing-based tests are performed on all NSCLCs. Though fragmented, this approach ensures testing for all current targetable genetic alterations is performed. Unfortunately, this style of testing is often incompatible with the limited amount of tumor tissue acquired by biopsy. In 2021, our institution implemented PGDx elio tissue complete (PGDx), introducing redundancy in ROS1 translocation testing, previously assessed by FISH through send-out testing to Mayo Clinic. The objective of this study was to perform a retrospective analysis of our molecular testing experience for NSCLC, with a spotlight on the nuances of ROS1 testing. Since its implementation at our institution, PGDx has been performed on 172 cases of NSCLC. As part of our NSCLC reflex testing agreement, ROS1 translocation FISH testing was also attempted on all cases. Of the 172 cases, one clinically actionable ROS1 translocation was identified by PGDx (0.5%). Interestingly, FISH testing for this case was equivocal. The remaining cases were negative for ROS1 translocations. Notably, FISH failed in six cases (3.5%) due to insufficient tissue. Three additional cases (1.7%) had minimal tumor tissue available for FISH testing (less than 300 cells), providing suboptimal results. Altogether, PGDx was successfully performed on all samples and, in the 166 cases where FISH was successful, there was no discordance between orthogonal tests. This supports the validity and reliability of PGDx in identifying clinically relevant rearrangements/fusions in ROS1. In this study, we demonstrate that PGDx can effectively replace FISH testing for ROS1 translocations in NSCLC. In addition to being technically equivalent to FISH for ROS1 with comparable turnaround times, PGDx adds substantial benefits. Replacing FISH testing with PGDx improves the diagnostic workflow, improves tissue utilization, and eliminates the costs associated with send-out orders. The cost of Mayo ROS1 FISH testing averages $520 per sample and this amount is billed to patient insurance, though reimbursements vary. Further, PGDx can detect the ROS1 gene fusion partners, a feature not possible through routine FISH testing in NSCLC. This added clinical information reduces the ambiguity of equivocal FISH results, exemplified by our study. By implementing this change, our institution will optimize both diagnostic practices and resource utilization in the clinical setting.

Concordance Between Platelet Expression Assay (PEA) and Serotonin Release Assay (SRA) in Heparin-Induced Thrombocytopenia: Implications for Diagnostic Accuracy and Laboratory Test Utilization

Abstract Introduction The Serotonin Release Assay (SRA) serves as the gold standard functional assay for heparin-induced thrombocytopenia (HIT) diagnosis at our institution. The present turnaround time (TAT) for SRA results ranges from 4-5 days, occasionally extending beyond 8 days, given outsourcing to a reference laboratory. Recently, an alternative functional assay, the Platelet Expression Assay (PEA), has been introduced. The PEA detects platelet activation through p-selectin expression by flow cytometry, with a reported sensitivity of 100% and specificity of 95% for HIT. The PEA is also a send-out test, and thus has similar TAT and cost profiles as the SRA, but with potential to transition into an in-house assay in the future. Herein, we sought to determine the concordance of the PEA and SRA for the detection and diagnosis of HIT within our patient population. Methods A retrospective review was conducted on all cases in which a HIT ELISA (screening immunoassay) was performed by the Special Coagulation Laboratory during a one-year period. A 4Ts score was calculated if not already documented by chart review. In a subset analysis, specimens with a positive screening ELISA were concurrently tested by both SRA and PEA to compare performance. Results Of the 1341 cases, a 4Ts score was calculated and found to be less than 4 for 30-50% of cases. A total of 490 cases were sent out for SRA, of which 49 (10%) returned positive results. In a subset analysis of 20 samples from 14 patients, all with positive ELISAs, results revealed concordance between the SRA and PEA for all but one sample (19/20, 95%). Specifically, three successive samples from one patient had [negative, negative, positive] results for SRA, and [negative, positive, positive] results for PEA, respectively. This discordant result suggests a potential difference in sensitivity between the two assays. Further subset analysis focused on an additional 13 samples from 10 patients, all with SRA-positive results. Only 8 samples were concordant (8/13, 62%). One case showed a negative PEA and presumed false positive SRA, given the clinical history, while 4 samples showed likely true positive SRA results, given strength of ELISA results and 4Ts score, but were negative by PEA. Conclusions The lack of adherence to the 4Ts score algorithm to drive laboratory test utilization resulted in unnecessary ELISA and functional assay testing, potentially resulting in increased costs and false positive results. This result underscores the need for vigilance in assessing and refining diagnostic strategies. Additionally, our discordant findings in the subset analysis underscore the importance of evaluating the concordance and discordance between SRA and PEA results, providing insights into the diagnostic accuracy and potential limitations of each assay in identifying HIT.

Utility of cell index in the diagnosis of healthcare-associated ventriculitis and meningitis: an analytical cross-sectional study

BackgroundThe diagnosis of healthcare-associated ventriculitis and meningitis (HCAVM) can be complex because multiple factors confound the interpretation of cerebrospinal fluid (CSF) tests. The cell index (CI) may help in the diagnosis of HCAVM. It does not incur additional medical cost and it avoids delays from the turnaround time of CSF cultures. It is derived by calculating the ratio of CSF white blood cell (WBC) and red blood cell (RBC) divided by the ratio of peripheral WBC and RBC. This study aimed to evaluate the diagnostic utility of this parameter.MethodsAn analytic, observational, cross-sectional study was conducted at the University of the Philippines – Philippine General Hospital. All admitted pediatric and adult patients from 2015 to 2022 who underwent external ventricular drain (EVD) insertion for hydrocephalus secondary to intracranial hemorrhage (ICH), acute ischemic stroke, intracranial neoplasms, traumatic brain injury, or congenital hydrocephalus were screened. Records of patients fulfilling the inclusion criteria were then reviewed.ResultsA total of 363 patients underwent EVD insertion from 2015 to 2022. Of these, 161 were included in the study. Two-thirds (66.5%) were adults ≥ 19 years old whereas the remaining were pediatric patients 1 to < 19 years old. There were no patients < 12 months old as they fulfilled at least one exclusion criteria. Forty-nine of them were later confirmed to have HCAVM based on the CDC/NHSN criteria. A CI cut-off of ≥ 1.21 gave a maximum sensitivity of 30.6% and specificity of 86.4%. Receiver operating characteristic area under the curve (AUC-ROC) analysis was 0.585. Subgroup analysis by age showed sensitivity of 52.9% in the pediatric age group and 3.13% in adults. Subgroup analysis by neurologic indication showed sensitivity of 27.6% for ICH and 35.0% for neoplasms. Subsequent AUC-ROC analyses, however, showed that CI failed to adequately diagnose HCAVM in these subgroups.ConclusionsIn our population of neurologic patients who underwent EVD insertion, the cell index is not a reliable parameter in the diagnosis of HCAVM.

Diagnostic Utility of Modified Method of AgNOR Staining in the Evaluation of Benign and Malignant Effusions

An exact identification of malignant cells in fluid by cytological examination is a well-known diagnostic challenge. One of the common problems is to distinguish reactive mesothelial cells from malignant cells. Conventional smears reported as ‘suspicious for malignancy’ indicate that the suspicious cases could not be classified with certainty as to whether they were reactive mesothelial cells or malignant cells. It poses problem in clinical staging of tumor, treatment and prognosis of malignancy. The purpose of the study was to determine the role of modified method of AgNOR staining in the evaluation of benign and malignant effusions. This cross-sectional study was conducted in the Department of Pathology, BIRDEM General Hospital, Dhaka, from July 2019 - June 2021. A total of 115 cases of effusion were included. All the samples were centrifuged and then smears were prepared from the deposit followed by staining with Hematoxylin &amp; Eosin stain, Papanicolaou stain and AgNOR stain. At first the diagnosis was made on conventional smear method. Then the findings were compared and analyzed by modified AgNOR staining method. In malignant cells, the mean AgNOR count was 5.59±1.05 (±SD) and the AgNORs were multiple and irregular in shape. On the other hand, in benign cells the AgNORs were comparatively larger, single dots with a mean count of 1.31±0.48.The AgNOR count method has definite role in differentiating benign from malignant effusion. This method has supportive value which can be utilized in differentiating malignant effusions from the benign ones, especially in suspicious cases.

The Predictability of Clinical Findings and Radiographs for Detecting Tarsal Coalition.

Tarsal coalition is a disorder of the foot characterized by the abnormal union between 2 or more of the tarsal bones. A minority of patients will develop pain and limited motion when reaching adolescence, for whom surgical resection of the coalition may be necessary. The diagnostic value of clinical and radiologic signs remains unclear. The aim of this study is to assess the predictive value of clinical symptoms and plain x-rays to diagnose tarsal coalition in symptomatic patients. We performed a retrospective chart review of patients with clinical suspicion of tarsal coalition between January 2011 and November 2019. Patient demographic data; clinical data on pain, limited motion, peroneal spasm, recurrent, or previous trauma; and radiologic data on the presence and type of coalition were collected. Multivariable general estimating equations analysis was used to assess associations between demographic and clinical characteristics and the likelihood of a positive coalition diagnosis. The study cohort was 336 patients (672 feet) with a mean age of 13 years and a 1:1 sex distribution. Thirt-eight percent of feet were diagnosed with a coalition of which 53% were talocalcaneal and 41% were calcaneonavicular. Coalitions were significantly more common in younger patients, males (OR 1.66, P=0.04), patients with lower BMI (OR 0.96, P=0.045), and patients who presented with painful feet (OR 1.59, P=0.04) or feet with limited motion (OR 7.49, P<0.001). Diagnostic utility of plain x-ray compared with CT diagnosis yielded a sensitivity of 76% and a specificity of 94%, with higher sensitivity (90%) in calcaneonavicular coalitions than in talocalcaneal (66%). Our study shows that limited subtalar movement, male sex, and low BMI have a high predictive value for tarsal coalition in symptomatic patients. Classic clinical findings that were not predictive of coalition in our cohort of symptomatic patients included peroneal spasm, recurrent ankle sprains, and recent trauma. Plain x-rays offer a reliable alternative to CT for diagnosis, especially for calcaneonavicular coalitions. Level III-retrospective comparative study.

Identification of novel biomarkers for atherosclerosis using single-cell RNA sequencing and machine learning.

Atherosclerosis (AS) is a predominant etiological factor in numerous cardiovascular diseases, with its associated complications such as myocardial infarction and stroke serving as major contributors to worldwide mortality rates. Here, we devised dependable AS-related biomarkers through the utilization of single-cell RNA sequencing, weighted co-expression network (WGCNA), and differential expression analysis. Furthermore, we employed various machine learning techniques (LASSO and SVM-RFE) to enhance the identification of AS biomarkers, subsequently validating them using the GEO dataset. Following this, CIBERSORT was employed to investigate the correlation between biomarkers and infiltrating immune cells. Consequently, 256 differentially expressed genes (DEGs) were selected in samples of AS and normal. GO and KEGG analyses indicated that these DEGs may be related to the negative regulation of leukocyte-mediated immunity, leukocyte cell-cell adhesion, and immune system processes. Notably, C1QC and COL1A1 were pinpointed as potential diagnostic markers for AS, a finding that was further validated in the GSE21545 dataset. Moreover, the area under the curve (AUC) values for these markers exceeded 0.8, underscoring their diagnostic utility. Analysis of immune cell infiltration revealed that the expression of C1QC was correlated with M0 macrophages, gamma delta T cells, activated mast cells and memory B cells. Similarly, COL1A1 expression was linked to M0 macrophages, memory B cells, activated mast cells, gamma delta T cells, and CD4 native T cells. Finally, these results were validated using mice and human samples through immunofluorescence, immunohistochemistry, and ELISA analysis. Overall, C1QC and COL1A1 would be potential biomarkers for AS diagnosis, and that would provides novel perspectives on the diagnosis and treatment of AS.

Left Ventricular Diastolic Dysfunction with Elevated Filling Pressures Is Associated with Embolic Stroke of Undetermined Source and Atrial Fibrillation.

Background/Objectives: Left ventricular diastolic dysfunction (LVDD) and elevated left ventricular filling pressure (LVFP) are strong predictors of clinical outcomes across various populations. However, their diagnostic utility in embolic stroke of undetermined source (ESUS) remains unclear. We hypothesized that LVDD with elevated LVFP (based on echocardiography) was more likely to be prevalent in ESUS compared to non-cardioembolic stroke (NCE) and to be associated with atrial fibrillation (AF) on follow-up monitoring. Methods: This is a single-center retrospective study that included adult patients with a diagnosis of acute ischemic stroke between January 2016 and June 2017. LV function was assessed by inpatient transthoracic echocardiogram (TTE), and stroke etiology was adjudicated by the neurologist per the consensus criteria. Patients with cardioembolic stroke and those with indeterminate diastolic function on TTE were excluded. Baseline patient characteristics and clinical variables were compared among patients with and without LVDD and elevated LVFP. Multivariable regression models were used to assess the associations between diastolic dysfunction, ESUS, and AF detection in ESUS patients. Results: We identified 509 patients with ESUS and NCE stroke who had reported diastolic function. The mean age was 64.19 years, 45.19% were female, and 146 had LVDD with available LVFP data. LVDD was not associated with ESUS (adjusted OR: 1.43, 95% CI: 0.90-2.27, p = 0.130) or atrial fibrillation (AF) detection on cardiac monitoring (adjusted OR: 1.88, 95% CI: 0.75-4.72, p = 0.179). However, LVDD with elevated LVFP was borderline associated with ESUS (adjusted OR: 2.17, 95% CI: 0.99-4.77, p = 0.054) and significantly associated with AF detection (adjusted OR: 3.59, 95% CI: 1.07-12.06, p = 0.038). Conclusions: Our data suggest that LVDD with elevated LVFP is borderline associated with ESUS and significantly associated with AF detection on follow-up cardiac monitoring. Therefore, the presence of LVDD with an increased probability of elevated LVFP may help identify a subset of stroke patients more likely to have ESUS, potentially due to atrial cardiopathy with underlying occult AF. Further studies are needed to confirm our findings and to evaluate the safety and efficacy of anticoagulation in patients with ESUS and LVDD with elevated LVFP.

Advancements in Hyperspectral Imaging and Computer-Aided Diagnostic Methods for the Enhanced Detection and Diagnosis of Head and Neck Cancer.

Background/Objectives: Head and neck cancer (HNC), predominantly squamous cell carcinoma (SCC), presents a significant global health burden. Conventional diagnostic approaches often face challenges in terms of achieving early detection and accurate diagnosis. This review examines recent advancements in hyperspectral imaging (HSI), integrated with computer-aided diagnostic (CAD) techniques, to enhance HNC detection and diagnosis. Methods: A systematic review of seven rigorously selected studies was performed. We focused on CAD algorithms, such as convolutional neural networks (CNNs), support vector machines (SVMs), and linear discriminant analysis (LDA). These are applicable to the hyperspectral imaging of HNC tissues. Results: The meta-analysis findings indicate that LDA surpasses other algorithms, achieving an accuracy of 92%, sensitivity of 91%, and specificity of 93%. CNNs exhibit moderate performance, with an accuracy of 82%, sensitivity of 77%, and specificity of 86%. SVMs demonstrate the lowest performance, with an accuracy of 76% and sensitivity of 48%, but maintain a high specificity level at 89%. Additionally, in vivo studies demonstrate superior performance when compared to ex vivo studies, reporting higher accuracy (81%), sensitivity (83%), and specificity (79%). Conclusion: Despite these promising findings, challenges persist, such as HSI's sensitivity to external conditions, the need for high-resolution and high-speed imaging, and the lack of comprehensive spectral databases. Future research should emphasize dimensionality reduction techniques, the integration of multiple machine learning models, and the development of extensive spectral libraries to enhance HSI's clinical utility in HNC diagnostics. This review underscores the transformative potential of HSI and CAD techniques in revolutionizing HNC diagnostics, facilitating more accurate and earlier detection, and improving patient outcomes.

Assessing the feasibility of ChatGPT-4o and Claude 3-Opus in thyroid nodule classification based on ultrasound images.

Large language models (LLMs) are pivotal in artificial intelligence, demonstrating advanced capabilities in natural language understanding and multimodal interactions, with significant potential in medical applications. This study explores the feasibility and efficacy of LLMs, specifically ChatGPT-4o and Claude 3-Opus, in classifying thyroid nodules using ultrasound images. This study included 112 patients with a total of 116 thyroid nodules, comprising 75 benign and 41 malignant cases. Ultrasound images of these nodules were analyzed using ChatGPT-4o and Claude 3-Opus to diagnose the benign or malignant nature of the nodules. An independent evaluation by a junior radiologist was also conducted. Diagnostic performance was assessed using Cohen's Kappa and receiver operating characteristic (ROC) curve analysis, referencing pathological diagnoses. ChatGPT-4o demonstrated poor agreement with pathological results (Kappa = 0.116), while Claude 3-Opus showed even lower agreement (Kappa = 0.034). The junior radiologist exhibited moderate agreement (Kappa = 0.450). ChatGPT-4o achieved an area under the ROC curve (AUC) of 57.0% (95% CI: 48.6-65.5%), slightly outperforming Claude 3-Opus (AUC of 52.0%, 95% CI: 43.2-60.9%). In contrast, the junior radiologist achieved a significantly higher AUC of 72.4% (95% CI: 63.7-81.1%). The unnecessary biopsy rates were 41.4% for ChatGPT-4o, 43.1% for Claude 3-Opus, and 12.1% for the junior radiologist. While LLMs such as ChatGPT-4o and Claude 3-Opus show promise for future applications in medical imaging, their current use in clinical diagnostics should be approached cautiously due to their limited accuracy.

A Clinical-Electrographic Profile of Neonatal Seizures and Their Etiologies in a Single Level III Neonatal Intensive Care Unit

Background: Seizures are the most frequent neurological emergency in neonatal period and can be associated with significant mortality and subsequent neuro-developmental disability if not recognized and managed early. Repaid identification of neonatal seizures and evaluation is critically required to identify and treat the underlying etiology. Clinicians face a major challenge in diagnosing and treating neonatal seizure because of inconspicuous clinical presentation, variable electro-clinical correlation. Assessing the combination of clinical presentation, etiological factors, different diagnostic tools, and treatments, can broaden the knowledge and understanding towards neonatal seizure providing better management and outcome. Objective: To study the characteristics of clinical and electrographic profile of neonatal seizure and the relations to their etiologies in neonatal intensive care unit. Methods: This is a descriptive cross sectional retrospective study of electronic health records with ICD- 10 diagnosis of neonatal seizure from birth to 28 days, who were admitted to neonatal intensive care unit at Sheikh Shakhbout Medical City between January 2020 to December 2021. Clinical data obtained including basic demographics: gender, gestational age, mode of delivery, birth weight, and Apgar score. Onset and type seizure, type of antiepileptic drugs administered, EEG findings, brain imaging, results of relevant laboratory tests and etiology of seizure were collected. Results: Total 31 neonates included in the study. Majority were male (71%), term (87%), and birth weight &gt;2,5 kg (90%). Seizure within 24 hours was 58% and semiology was focal clonic in 32% of patient. No events in EEG in 81% and 6% had electrographic seizure (n=2). 94 % were treated with anti-convulsant, 86% of them before EEG. The majority (86%) received phenobarbitone as 1st line treatment and 83% received monotherapy. Leading causes of seizure were HIE (48%) followed by Vascular causes (16%). Seizure within 24 hours caused mainly by HIE (61%) and 60% of neonates with vascular and all infectious and genetic causes had seizure after 24 hours. In vascular causes, (60%) presented with focal clonic seizure. 60% of Multifocal epileptiform activity seen in HIE whereas focal presented more in vascular patient (36%). In HIE cases, 53% had normal brain MRI and 47% were abnormal. All cases with vascular causes had diagnostic abnormal MRI. The majority of HIE cases (87%) and all vascular cases received monotherapy. Conclusion: In this descriptive study of neonatal seizure, certain demographic data, clinical and electrographic characteristics had established links to their etiologies. Clinical events captured during EEG with no electrographic seizure are classified as non-epileptic clinical phenomenon. Diagnostic utility of EEG is required in diagnosis of involuntary movements and avoid unnecessary anti-seizure medications. Understanding the clinical-electrographic profile of neonatal seizure helps in the early recognition of specific etiologies, allowing an early diagnosis by organized diagnostic approach and management.

Comparative diagnostic utility of Rockall and Glasgow-Blatchford scores in non-variceal upper gastrointestinal bleeding: a systematic review and meta-analysis.

The Rockall score and Glasgow-Blatchford score (GBS) are two scoring systems validated in the evaluation of upper gastrointestinal bleeding (UGIB). However, no meta-analysis exists to summarize the current data and clarify the use of Rockall score and GBS focusing on non-variceal UGIB. We aimed to evaluate and compare the utility of the Rockall score and GBS in predicting clinical outcomes in non-variceal UGIB. We conducted a systematic review and meta-analysis, searching the MEDLINE and EMBASE databases for all peer-reviewed articles using the terms including 'Glasgow-Blatchford', 'Rockall', and 'gastrointestinal bleed' from their inception to 22 March 2023. Outcomes included mortality, rebleeding, need for blood transfusion, and need for surgical intervention. Seven studies with 755 participants with non-variceal bleeding were included in the analysis. Pooled analysis demonstrated no difference in the area under the receiver operating characteristic (AUROC) between GBS and Rockall score to predict mortality [weighted mean difference (WMD) = 0.01, 95% CI: -0.06 to 0.08] or rebleeding (WMD = 0.04, 95% CI: -0.03 to 0.11). GBS had a higher AUROC to predict the outcomes compared to Rockall score for the needs for transfusion (WMD = 0.09, 95% CI: 0.01-0.16) and surgical intervention (WMD = 0.21, 95% CI: 0.14-0.29). The GBS could be superior to the Rockall score in predicting the needs for transfusion and surgical intervention in non-variceal UGIB. However, both scores demonstrate low performance for predicting mortality or rebleeding.

Diagnostic utility of ESR1 mutation detection in liquid biopsy of metastatic breast cancer patients.

Molecular analysis of circulating cell-free DNA (cfDNA) extracted from peripheral blood plasma samples of metastatic breast cancer (BC) patients is of rising interest to find optimal therapeutic strategies. Detection of emerging resistance mutations against endocrine therapy is possible with this approach. Here we present the applicability of a laboratory-developed NGS assay in molecular pathology routine diagnostic, covering four genes with therapeutic (ESR1, PIK3CA, ERBB2) and prognostic (TP53) consequences in metastatic BC. We analyzed 162 liquid biopsy samples and 25 corresponding metastases from metastatic BC patients. In the liquid biopsies, we detected ESR1 mutations in 42 cases (25.9%) and ERBB2 mutations in six cases (3.7%), arguing for a change in therapy to fulvestrant, elacestrant, or neratinib. Furthermore, 17 cases had detectable TP53 mutations, associated with resistance against endocrine therapy. We conclude that liquid biopsy testing is a noninvasive, sensitive, and helpful method to optimize therapeutic decisions in metastatic BC.

Risk Factors Associated With Exaggerated Blood Pressure Response At The Time Of Exercise Treadmill Stress Test.

Exaggerated blood pressure response (EBPR) to exercise stress testing (EST) may be a marker of future hypertension and carry valuable information for the prediction of cardiovascular events. We sought to evaluate the clinical and resting EST parameters associated with increased likelihood to EBPR. The records of 14073 patients (mean age: 55±11 years) without known cardiovascular disease who underwent a treadmill EST were analysed. The overall prevalence of arterial hypertension was 44%. A considerable proportion (24%) of patients exhibited EBPR. Multivariate analysis of the entire study population showed that middle-aged individuals (40-60 years old), resting systolic BP>130mmHg and/or diastolic BP>80 mmHg, known arterial hypertension, current cigarette smoking and family history of premature coronary artery disease are all independent risk factors for EBPR (all P<0.001). Although the presence of arterial hypertension increased the likelihood of EBPR in the analysis of the entire population, the relevant association in subjects above 60 years old is statistically non-significant (P=0.120). Notably, the pre-test systolic BP>130mmHg and/or diastolic BP>80 mmHg level increased significantly the likelihood to manifest EBPR in all age categories (<40, 40-60 and >60 years old) independent of hypertension presence and in all hypertensive patients independently of antihypertension treatment intake (all P<0.001). Considering the diagnostic and prognostic utility of EBPR during treadmill EST the clinical and resting haemodynamic parameters that increase the likelihood to EBPR are targets for interventions and preventive measures to modify lifestyle risk behaviours and reduce hypertension and cardiovascular risk factors in the early stages.

Evaluation of the Seegene Allplex™ RV master assay for one-step simultaneous detection of eight respiratory viruses in nasopharyngeal specimens

BackgroundThe Seegene Allplex™ RV Master (RVM) assay is a one-step multiplex real-time reverse transcription polymerase chain reaction (RT-PCR) system for detecting eight viral respiratory pathogens from nasopharyngeal swab, aspirate, and bronchoalveolar lavage specimens. The eight RVM targets are: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Influenza A (Flu A), Influenza B (Flu B), Human respiratory syncytial virus (RSV), adenovirus (AdV), rhinovirus (HRV), parainfluenza virus (PIV), and metapneumovirus (MPV). The assay is based on Seegene’s multiple detection temperature (MuDT) technology and provides cycle threshold (Ct) values for each of its viral targets upon PCR completion. ObjectiveWe aimed to evaluate the diagnostic performance of the RVM assay by calculating sensitivity, specificity, accuracy, Positive Predictive Value (PPV), Negative Predictive Value (NPV), Positive Percent Agreement (PPA), Negative Percent Agreement (NPA), and Overall Percent Agreement (OPA) compared to definite diagnosis and analogous reference assays. Study designDiagnostic sensitivity, specificity, accuracy, PPV, and NPV were calculated by comparing the results of the RVM assay to that of definite diagnosis assays; while PPA, NPA, and OPA were calculated by comparing results of the RVM assay to that of analogous reference products. Definite diagnosis and reference methods comprised whole genome sequencing and PCR genotyping, the Allplex™ SARS-CoV-2/FluA/FluB/RSV and Respiratory Panels 1, 2, and 3 assays (Seegene), and the Xpert® Xpress SARS-CoV-2/FluA/FluB/RSV Plus assay (Cepheid). Reproducibility of the RVM assay using fully-automated and semi-automated nucleic acid (NA) extraction workflows and as performed by independent operators was also assessed. In total, 249 positive respiratory specimens and at least 50 negative specimens for each target tested were used for this evaluation study. ResultsSensitivity, specificity, accuracy, PPV, NPV, PPA, NPA, and OPA ranged from 95.7 % to 100 % for detecting all eight targets tested on the RVM assay. Reproducibility PPA, NPA, and OPA between automated and semi-automated NA extraction workflows were all >97.9 %, while the reproducibility PPA, NPA and OPA between independent operators were all 100 %. ConclusionThese results demonstrate a high level of sensitivity, specificity, accuracy and diagnostic predictive value of the RVM assay and high agreement with comparable reference assays in identifying all eight of its targets. Taken together, our study underscores the diagnostic utility of the RVM assay in detecting eight viral respiratory pathogens.

Diagnostic Utility of Canine C-Reactive Protein, Haptoglobin, and 25-Hydroxyvitamin-D in Dogs with Nasal Cavity Disease

In this prospective blinded study, canine C-reactive protein (c-CRP), haptoglobin (HPT), and 25-hydroxyvitamin-D (25(OH)D) were investigated for their diagnostic value in 55 dogs with nasal cavity disease (ND). After comprehensive diagnostics including a culture-dependent microbiological examination (ME) of nasal swabs, 17 dogs were excluded due to additionally detected systemic diseases or steroid pre-treatment. Included were 25 dogs with malignant ND (13 carcinomas and 12 sarcomas) and 30 dogs with benign ND (7 benign tumors, 13 idiopathic rhinitis (IR), and 10 others), as well as 10 controls. In none of the 72 dogs with ND was primary bacterial rhinitis diagnosed. Although within the reference interval, compared to the controls, c-CRP was significantly higher in dogs with ND in general and in every subgroup except for benign tumors. Serum HPT concentrations were not different among groups. Compared to the controls, 25(OH)D concentrations were significantly lower (p = 0.041) in malignant ND and sarcomas (p = 0.025). Despite pre-treatment with antibiotics (40/54; 74.1%), in 23/51 (45%) dogs, the ME was positive. Cultivated bacteria did not differ significantly between nasal diseases. The serum markers were not significantly different regarding the positivity of ME. In conclusion, the investigated serum markers were not clinically useful for the reliable detection of canine ND, as was the ME. Because of the low number of dogs with IR and positive or negative ME, further studies regarding c-CRP are needed in a larger group of IR dogs without concomitant diseases to reliably evaluate its utility in IR dogs with suspected secondary bacterial nasal infection.

Utility of diffusion-weighted imaging in differentiating benign and malignant breast lesions.

Breast cancer presents a significant global health burden. An accurate differentiation between benign and malignant lesions is imperative for timely intervention. While dynamic contrast enhanced MRI (DCE-MRI) is highly sensitive, its specificity is limited. This has led to the exploration of diffusion-weighted imaging (DWI) in distinguishing between benign and malignant breast lesions. The study aimed to explore the diagnostic utility of DWI in distinguishing between benign and malignant breast lesions. Assessment of 38 breast lesions using DWI with a b value of 800 s/mm2, performed with 3 Tesla MRI. The diagnostic performance of two different region of Interest (ROI) placement approaches was compared to obtain a feasible cut-off value of apparent diffusion coefficient (ADC) to differentiate between malignant and benign lesions. The histopathological reports were used as the gold standard. ADC values of malignant lesions were significantly lower than those of benign lesions (0.84 × 10-3 mm2/s vs. 1.54 × 10-3 mm2/s). The average ADC measured using a small-sized 2D ROI including the darkest part in the ADC map, performed better than the large 2D ROI covering the entire lesion. Using a cut-off value of 0.98 × 10-3 mm2/s, ADC obtained high sensitivity (90%) and specificity (88.9%) in distinguishing between benign and malignant breast lesions. Utilising quantitative analysis of DWI with ADC value measurement, reliably distinguished between benign and malignant breast lesions in this cohort, especially when employing a higher b value of 800 s/mm2.

An Appraisal of Recurrent Miscarriage in Sub-Saharan Africa: Occurrence and Possible Solution

A recurrent miscarriage may be defined in the African context as the foetal demise of two or more successive pregnancies before the attainment of the age of viability. A literature review was done to assess the trend of recurrent miscarriage in sub-Saharan Africa. Identifying the main causes, considering the population at risk, and the availability of accurate diagnostic utilities to effectively ensure good management of recurrent miscarriage is an important gynaecologic issue. Over the years, studies have identified several etiologies and yet there’s been no tangible implementation of therapeutic strategies. Routine modifications should also be employed to develop new approaches to reproductive prognosis. There is notably scanty information on the cases of spontaneous abortion due to chromosomal abnormalities. Genetic and immunological factors should be considered in the work-up plan for women with RM. About 70% of the cases of RM are considered unexplained, and this may be due to limited resources. We concluded that there is relatively poor management of miscarriage and cases of missed and inaccurate diagnosis of the causes of spontaneous abortion in sub-Saharan Africa. More studies are needed in order to assess the extent of genetic induced miscarriage, where resources are limited, folic acid supplements should be provided for pregnant women.

Matched Oligoclonal Bands: Diagnostic Utility and Clinical Characteristics

Matched Oligoclonal Bands: Diagnostic Utility and Clinical Characteristics

The Use of Language Sample Analysis to Differentiate Developmental Language Disorder From Typical Language in Bilingual Children: A Systematic Review and Meta-Analysis.

Language sample analysis (LSA) is a commonly recommended method of assessment for bilingual children. This systematic review and meta-analysis provides a comprehensive overview of the literature on the use of LSA to differentiate between developmental language disorder (DLD) and typical language (TL) in bilingual children. We conducted a search of several large electronic databases along with forward and backward searches and applied abstract and full-text screening procedures to identify all relevant studies. We then estimated standardized mean differences, representing the ability of LSA to differentiate between DLD and TL, using multilevel model and subgroup and moderator analyses to identify characteristics of LSA that may be associated with differences in effect size magnitude. We conducted assessments of publication bias and risk of bias by examining quality indicators for each study. The search yielded 35 articles that met the inclusion criteria. Participants ranged in age from 2;0 (years;months) to 11;9, with over 40 languages represented. Across studies, the pooled standardized mean difference indicated that children with DLD performed 0.78 SD lower on LSA measures than those with TL. Measures of morphosyntactic accuracy exhibited the largest pooled effect size. Elicitation method, language of task, and age were not associated with differences in effect size. Results of this study provide evidence of the clinical utility of LSA in differentiating between DLD and TL in bilingual children. Further research is needed to examine classification accuracy as well as task characteristics that may improve its diagnostic utility.

Clinical Predilection Features of Middle Ear Adenomatous Neuroendocrine Tumors: A Review of 10 Patients and a Special Case Is Attached.

Introduction: Middle ear adenomatous neuroendocrine tumors (MEANTs) are rare middle ear lesions characterized by nonspecific symptoms, signs, and imaging findings. Diagnosis typically relies on postoperative pathological assessment. This study investigated the diagnostic utility of the predilection sites and clinical characteristics of MEANTs. Methods: A retrospective analysis was conducted on clinical data from 10 patients with histologically confirmed MEANTs, admitted to Eye & ENT Hospital of Fudan University between March 2016 and March 2023. Results: The median age of the patients at diagnosis was 39.3 years. Hearing loss (n = 8) and ear pain (n = 6) were the most prevalent clinical symptoms in the patients diagnosed with MEANTs. Endoscopic examination revealed diverse symptoms, predominantly presenting as non-pulsatile masses with distinct boundaries and quasi-circular shapes within the external auditory canal, often accompanied by abundant blood vessels (n = 4). Tumors were typically confined to the middle/lower tympanic chambers or eustachian tube and were frequently associated with tympanic sclerosis, particularly around the pharyngeal tube (n = 3). Pathologically, MEANTs exhibited CD56 positivity or weak positivity, along with positive staining for CKpan and Syn, negativity for S100, and Ki67 ≤3%. Personalized surgical interventions were chosen by all the patients based on lesion severity, with no subsequent radiotherapy or chemotherapy administered postoperatively. No tumor progression was noted during the postoperative follow-up. In addition, a noteworthy case was presented in which MEANT initially manifested in the middle or lower tympanic cavity and eustachian tubes. Over 2 years, the tumor progressively grew, invading the middle tympanum and surrounding ossicles, ultimately achieving complete resection with no recurrence observed during subsequent follow-up. Conclusions: A possible diagnosis of middle ear adenoma should be considered when encountering non-pulsatile tumors with clearly demarcated inner boundaries within the external auditory canal accompanied by abundant quasi-circular vessels and the presence of new bone or neoplasm at the pharyngeal tympanic canal orifice observed during preoperative examinations or surgical procedures.