Utility Of Diagnostic Tests Research Articles

Diagnostic Utility of Combining Homocysteine, Lipoprotein-Associated Phospholipase A2, and the C-Reactive Protein-to-Albumin Ratio for Assessing Carotid Atherosclerosis and Plaque Stability in Patients with Essential Hypertension.

The objective of this study is to determine the diagnostic utility of combining homocysteine (HCY), lipoprotein-associated phospholipase A2 (LP-PLA2), and the C-reactive protein-to-albumin ratio (CAR) for carotid atherosclerosis (CAS) and plaque stability in patients with essential hypertension (EH). A total of 280 patients with EH were divided into 2 groups according to ultrasound diagnosis: CAS (n = 106) and non-CAS (N-CAS [n = 174]). The CAS group was further segmented into plaque-stable (n = 50) and plaque non-stable (n = 56) groups. General data were collected for all patients. Risk factors associated with CAS and plaque instability in patients with EH, and the diagnostic utility of HCY, LP-PLA2, and CAR testing alone, or in combination, for assessing CAS and plaque instability were determined. Mean age, systolic blood pressure (SBP), duration of EH, smoking, total cholesterol high-density lipoprotein cholesterol, HCY, LP-PLA2 levels, and CAR were higher in the CAS group than those in the N-CAS group (P < 0.05). SBP, duration of EH, HCY and LP-PLA2 levels, and CAR were independent risk factors for CAS (P < 0.05). In addition, HCY, LP-PLA2, and CAR alone demonstrated significant diagnostic efficacy (P < 0.001) but were inferior to the combined diagnostic utility of the 3 parameters (P < 0.001). HCY and LP-PLA2 levels, and CAR were higher in the plaque non-stable than in the plaque-stable group (P < 0.05). Duration of EH, low-density lipoprotein cholesterol, HCY, LP-PLA2, and CAR independently influenced plaque instability in patients with CAS (P < 0.05). The combined diagnostic utility of HCY, LP-PLA2, and CAR (P < 0.001) was superior to that of each parameter alone and demonstrated more pronounced diagnostic efficacy (P < 0.001). HCY, LP-PLA2, and CAR were independent risk factors for CAS and plaque instability in patients with EH. HCY, LP-PLA2, and CAR demonstrated significant diagnostic efficacy for CAS and plaque instability, and combination of the 3 demonstrated the most pronounced diagnostic efficacy.

Antimicrobial prescribing practices and factors associated with antimicrobial prescribing in hospitalized COVID-19 patients in Oyo state: A retrospective study.

Proportion of hospitalized COVID-19 patients receiving antimicrobial drug is significantly high despite evidence of low level of actual bacterial co-infection, potentially contributing to poor health outcome and global antimicrobial resistance. A retrospective study was performed on antimicrobial agents prescribed to adult patients with confirmed COVID-19 admitted across three isolation facilities between 1 March 2020 and 30 April 2021 in Ibadan, Oyo state, Nigeria. From individual records, we evaluated patient demographics, COVID-19 risk factors, diagnostic testing, disease severity and antimicrobial utilization. The primary aim was to determine the prevalence of antimicrobial prescription as well as factors associated with antimicrobial prescribing in hospitalized patients with COVID-19 in Oyo state. In total, 271 patients were included in this study. The median age of the population was 51 years (IQR; 32-62 years). The mean duration of hospital admission was 13 days (IQR: 10-14 days). Majority of participants were symptomatic (81.5%). All participants had a COVID-19 PCR test performed and none had bacterial culture performed. All patients received antimicrobial therapy across the entire cohort. The mean DOT per LOT across cohorts was 1.2 for mild cases, 1.4 for moderate cases and 1.3 for severe cases. Factors associated with the number of antimicrobials per prescription were being single (P = 0.02), being below 60 years of age (P = 0.04), mild COVID-19 symptoms (P < 0.001) and diabetes comorbidity (P = 0.03). Given the high rate of antimicrobial prescription and absence of bacteriological culture analysis in these patients, there is risk of development and spread of antimicrobial resistant. Continuous review of antimicrobial prescription is critical in the management of hospitalized COVID-19 patients.

Utilization of Syndromic Vaginitis Diagnostic Testing Reduces 6-Month Follow-Up Outpatient Service Healthcare Costs—A Real-World Data Analysis

Background/Objectives: Vaginitis is a common infection among women of reproductive age. Although various diagnostic methodologies exist, diagnosis without the utilization of available diagnostic tests remains prevalent. This study aimed to assess downstream healthcare utilization and the cost of patients with and without diagnostic testing. Methods: This retrospective, observational study utilized the IQVIA PharMetrics® Plus database from July 2020 to October 2023. Patients with an index claim (ICD-10 code indicating vaginitis) were categorized into two cohorts: those who received a syndromic polymerase chain reaction (PCR) test and those who had no documented test on the index date or within two days. Total and service-specific healthcare resource utilization and costs were assessed for 6 months following the index event. This study was designed to inform how Syndromic Vaginitis PCR testing is used to make treatment decisions and to track outpatient and inpatient healthcare utilization for 6 months post index date represented by cost. Results: Patients who received a Syndromic Vaginitis PCR test had significantly fewer outpatient medical services in the 6 months following initial diagnosis compared to those who received no diagnostic test. This was largely attributed to a substantial decrease in other medical service visits, resulting in mean cost savings of USD 2067 (Syndromic PCR = USD 6675, SD = USD 17,187; No Test = USD 8742, SD = USD 29,894) (p-value 0.0009). Conclusions: Many vaginitis patients do not receive testing, but Syndromic Vaginitis PCR testing may be an effective diagnostic tool for reducing costs associated with vaginitis infections.

Diagnostic utility of rapid antigen testing as point-of-care test for influenza and other respiratory viruses in patients with acute respiratory illness

This study investigates the prevalence and clinical characteristics of respiratory viruses among patients with acute respiratory illness (ARI) in a low-resource setting, using a rapid antigen test as a point-of-care test (POCT). We included 343 patients presenting with ARI symptoms at an outpatient pulmonary clinic from December 2023 to April 2024. Nasopharyngeal swabs were tested for SARS-CoV-2, influenza A/B, respiratory syncytial virus, and adenovirus using POCT. The overall prevalence of respiratory viruses was 21.2%, with influenza A being the most common (11.4%). Shorter duration of symptoms and lower lymphocyte counts were associated with higher influenza positivity. Patients who tested positive for influenza received significantly more antiviral therapy (98.1% vs. 39.4%, p<0.001) and less antibiotic therapy (1.9% vs. 28.5%, p<0.001) compared to those who tested negative. The study highlights the utility of rapid antigen testing in enhancing antiviral and antibiotic stewardship, thereby improving clinical decision-making and patient outcomes in resource-limited settings.

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.

Comparative Analysis of Diagnostic Methods for Tuberculosis in an HIV-Positive Patient with Acute Respiratory Failure

Aims: To compare the diagnostic utility of TB LAM testing against the gold standard BAL with GeneXpert in a critically ill patient with advanced HIV. Methodology: A case report of a 28-year-old man with severe respiratory distress, confirmed HIV (CD4 count of 12 cells/cc³), and negative TB LAM test. Initial treatments included caspofungin, ampicillin-sulbactam, and cotrimoxazole forte. Imaging showed alveolar consolidations, and blood cultures were negative. Results: Notwithstanding the application of empirically validated therapeutic interventions targeting tuberculosis (TB), fungal infections, and Pneumocystis jirovecii, the patient's clinical status progressively deteriorated, culminating in fatality. Scientific Novelty: This case highlighted the need for combining urine LAM testing with GeneXpert for accurate TB diagnosis in advanced HIV patients. Conclusion: GeneXpert is essential for confirming TB and rifampicin resistance, while urine LAM should be complemented with additional tests when clinical suspicion remains high. Incorporating these assessments elevates diagnostic precision and improves patient prognoses.

Diagnostic Yield and Clinical Utility of Genomic Testing in Patients with Suspected Genetic Kidney Disease: Singapore's First-Year Experience

Diagnostic Yield and Clinical Utility of Genomic Testing in Patients with Suspected Genetic Kidney Disease: Singapore's First-Year Experience

Association of a Novel Electronic Form for Preoperative Cardiac Risk Assessment With Reduction in Cardiac Consultations and Testing: Retrospective Cohort Study.

Preoperative cardiac risk assessment is an integral part of preoperative evaluation; however, there is significant variation among providers, leading to inappropriate referrals for cardiology consultation or excessive low-value cardiac testing. We implemented a novel electronic medical record (EMR) form in our preoperative clinics to decrease variation. This study aimed to investigate the impact of the EMR form on the preoperative utilization of cardiology consultation and cardiac diagnostic testing (echocardiograms, stress tests, and cardiac catheterization) and evaluate postoperative outcomes. A retrospective cohort study was conducted. Patients who underwent outpatient preoperative evaluation prior to an elective surgery over 2 years were divided into 2 cohorts: from July 1, 2021, to June 30, 2022 (pre-EMR form implementation), and from July 1, 2022, to June 30, 2023 (post-EMR form implementation). Demographics, comorbidities, resource utilization, and surgical characteristics were analyzed. Propensity score matching was used to adjust for differences between the 2 cohorts. The primary outcomes were the utilization of preoperative cardiology consultation, cardiac testing, and 30-day postoperative major adverse cardiac events (MACE). A total of 25,484 patients met the inclusion criteria. Propensity score matching yielded 11,645 well-matched pairs. The post-EMR form, matched cohort had lower cardiology consultation (pre-EMR form: n=2698, 23.2% vs post-EMR form: n=2088, 17.9%; P<.001) and echocardiogram (pre-EMR form: n=808, 6.9% vs post-EMR form: n=591, 5.1%; P<.001) utilization. There were no significant differences in the 30-day postoperative outcomes, including MACE (all P>.05). While patients with "possible indications" for cardiology consultation had higher MACE rates, the consultations did not reduce MACE risk. Most algorithm end points, except for active cardiac conditions, had MACE rates <1%. In this cohort study, preoperative cardiac risk assessment using a novel EMR form was associated with a significant decrease in cardiology consultation and testing utilization, with no adverse impact on postoperative outcomes. Adopting this approach may assist perioperative medicine clinicians and anesthesiologists in efficiently decreasing unnecessary preoperative resource utilization without compromising patient safety or quality of care.

A vision to the future: value-based laboratory medicine.

The ultimate goal of value-based laboratory medicine is maximizing the effectiveness of laboratory tests in improving patient outcomes, optimizing resources and minimizing unnecessary costs. This approach abandons the oversimplified notion of test volume and cost, in favor of emphasizing the clinical utility and quality of diagnostic tests in the clinical decision-making. Several key elements characterize value-based laboratory medicine, which can be summarized in some basic concepts, such as organization of invitro diagnostics (including appropriateness, integrated diagnostics, networking, remote patient monitoring, disruptive innovations), translation of laboratory data into clinical information and measurable outcomes, sustainability, reimbursement, ethics (e.g., patient empowerment and safety, data protection, analysis of big data, scientific publishing). Education and training are also crucial, along with considerations for the future of the profession, which will be largely influenced by advances in automation, information technology, artificial intelligence, and regulations concerning invitro diagnostics. This collective opinion paper, composed of summaries from presentations given at the two-day European Federation of Laboratory Medicine (EFLM) Strategic Conference "A vision to the future: value-based laboratory medicine" (Padova, Italy; September 23-24, 2024), aims to provide a comprehensive overview of value-based laboratory medicine, projecting the profession into a more clinically effective and sustainable future.

Factors associated with antibiotics for respiratory infections in Swiss long-term care facilities

ObjectivesTo identify factors contributing to general and inappropriate antibiotic prescription among long-term care facility (LTCF) residents with lower respiratory tract infections (LRTI). MethodsProspective multicentric observational study. Residents with LRTI were recruited among 32 LTCFs in Western Switzerland during winter 2022-2023. Residents underwent lung ultrasound (LUS) within three days of LRTI onset, serving as the pneumonia diagnosis reference standard. To identify factors among demographics, vital signs, diagnostic tests, and LTCF characteristics associated with (i) antibiotic prescription and (ii) inappropriate prescription, we used multivariable logistic regression and backward selection with a p-value cutoff of <0.1. ResultsWe included 114 residents, 63% female, median age of 87 years. Overall, 59 (52%) residents had diagnostic tests performed: 50 (44%) had a PCR for respiratory viruses and 16 (14%) had a blood test with CRP and/or blood count. A total of 63 (55%) residents received antibiotics.Factors associated with antibiotic prescriptions were CFS ≥ 7 (aOR 6.8, 95% CI 1.5-24.4), oxygen saturation < 92% (3.5, 1.4-8.8), performing a blood test (0.1, 0.0-0.6), rural LTCFs (0.3, 0.1-0.7), and female physician (0.3, 0.1-0.8). Among residents receiving antibiotics, 48 (74%) had inappropriate prescriptions, with as only protective factor performing a respiratory virus PCR test (0.1, 0.0-0.4). Conclusions and ImplicationsWhile half of LRTI residents received antibiotics, falling within lower ranges of European LTCFs prescription rates (53-80%), most antibiotic prescriptions were inappropriate. Utilization of diagnostic tests correlates with lower overall and inappropriate prescription, advocating for their use to optimize prescription practices in LTCFs.

Diagnostic and clinical utility of comprehensive multigene panel testing for patients with neuropathy.

Prior to next-generation sequencing (NGS), the evaluation of a patient with neuropathy typically consisted of screening for acquired causes, followed by clinical genetic testing of PMP22, MFN2, GJB1, and MPZ in patients with a positive family history and symptom onset prior to age 50. In this study, we examined the clinical utility of NGS in a large cohort of patients analyzed in a commercial laboratory. A cohort of 6849 adult patients underwent clinician-ordered peripheral neuropathy multigene panel testing ranging from 66 to 111 genes that included NGS and intragenic deletion/duplication analysis. A molecular diagnosis was identified for 8.4% of the cohort (n = 573/6849). Variants in PMP22, MFN2, GJB1, MPZ, and TTR accounted for 73.8% of molecular diagnoses. Results had potential clinical actionability for 398 (69.5%) patients. Our results suggest that 225/573 (39.3%) of molecular diagnoses and 113/398 (28.4%) of clinical interventions would have been missed if the testing approach had been restricted to older guidelines. Our results highlight the need for expanded genetic testing guidelines that account for the increased number of genes associated with hereditary neuropathy, address the overlap of acquired and hereditary neuropathy, and provide broader access to genetic diagnosis for patients.

Diagnostic utility of multimodal advanced molecular testing to classify metastases of unknown primaries: A case of a patient with no known medical history.

Diagnostic utility of multimodal advanced molecular testing to classify metastases of unknown primaries: A case of a patient with no known medical history.

A multimodal approach to diagnosis of neuromuscular neosporosis in dogs.

Early diagnosis of neosporosis in dogs is challenging. To evaluate the feasibility of a compound multimodal testing approach for diagnosing in dogs neuromuscular and combined forms of neosporosis. A total of 16 dogs diagnosed with solely neuromuscular neosporosis or with a combination of neuromuscular and central nervous system neosporosis. Retrospective review of clinical signs, laboratory findings, treatment, and outcome with focus on the diagnostic utility of different tests. Development of a chromogenic in situ hybridization (ISH) assay for the identification of Neospora caninum in paraffin-embedded muscle samples. 13/16 dogs had only neuromuscular signs of neosporosis, 3/16 had disease signs with concomitant central nervous system (CNS) involvement. Serology was performed in 15/16, with 10/15 showing titers >1 : 160 at admission. PCR on muscle samples detected N. caninum DNA in 11/16. Immunohistochemistry (IHC) detected N. caninum in 9/16 and ISH in 9/16. Histopathology revealed inflammatory myopathy in 10/16, necrotizing myopathy in 5/16, borderline changes in 1/16 and tachyzoites in 9/16. In 4 cases, N. caninum infection was confirmed with all 5 diagnostic methods, 3 cases with 4, 2 with 3, 6 with 2, and 1 animal with 1. Diagnosis of N. caninum infection should rely on a multimodal diagnostic approach and negativity of 1 single test should not allow for exclusion. Serology in combination with direct parasite identification via histopathology, DNA via PCR, or both modalities, appears a reliable diagnostic approach.

Disparities in glaucoma and macular degeneration healthcare utilization among persons living with dementia in the United States.

Dementia is common among patients with primary open angle glaucoma (POAG) and neovascular age-related macular degeneration (nAMD). This study compares visit frequency, diagnostic test utilization, and treatment patterns for POAG and nAMD among persons with vs. without dementia. Optum's de-identified Clinformatics® Data Mart Database (January 1, 2000-June 30, 2022) was used for this study. Two cohorts were created from newly diagnosed POAG or nAMD patients. Within each cohort, an exposure cohort was created of newly diagnosed dementia patients. The primary outcome was the number of visits to an eye care provider. Secondary analyses for the POAG cohort assessed the number of visual field tests, optical coherence tomography (OCT), and glaucoma medication prescription coverage. The secondary analysis for the nAMD cohort included the number of injections performed. Poisson regression was used to determine the relative rates of outcomes. POAG patients with dementia had reduced rates of eye care visits (RR 0.76, 95% CI: 0.75-0.77), lower rates of testing utilization for visual fields (RR 0.66, 95% CI: 0.63-0.68) and OCT (RR 0.67, 95% CI: 0.64-0.69), and a lower rate of glaucoma prescription medication coverage (RR 0.83, 95% CI: 0.83-0.83). nAMD patients with dementia had reduced rates of eye care visits (RR 0.74, 95% CI: 0.70-0.79) and received fewer intravitreal injections (RR 0.64, 95% CI: 0.58-0.69) than those without dementia. POAG and nAMD patients with dementia obtained less eye care and less monitoring and treatment of their disease. These findings suggest that this population may be vulnerable to gaps in ophthalmic care.

The Utility of Genetic Testing in Infantile Epileptic Spasms Syndrome: A Step-Based Approach in the Next-Generation Sequencing Era

BackgroundTo evaluate the utility of genetic testing for etiology-specific diagnosis (ESD) in infantile epileptic spasms syndrome (IESS) with a step-based diagnostic approach in the next-generation sequencing (NGS) era. MethodsThe study cohort consisted of 314 patients with IESS, followed by the Pediatric Neurology Division of Ege University Hospital between 2005 and 2021. The ESD was evaluated using a step-based approach: step I (clinical phenomenology), step II (neuroimaging), step III (metabolic screening), and step IV (genetic testing). The diagnostic utility of genetic testing was evaluated to compare the early-NGS period (2005 to 2013, n = 183) and the NGS era (2014 to 2021, n = 131). ResultsAn ESD was established in 221 of 314 (70.4%) infants with IESS: structural, 40.8%; genetic, 17.2%; metabolic, 8.3%; immune-infectious, 4.1%. The diagnostic yield of genetic testing increased from 8.9% to 41.7% in the cohort during the four follow-up periods. The rate of unknown etiology decreased from 34.9% to 22.1% during the follow-up periods. The genetic ESD was established as 27.4% with genetic testing in the NGS era. The genetic testing in the NGS era increased dramatically in subgroups with unknown and structural etiologies. The diagnostic yields of the epilepsy panels increased from 7.6% to 19.2%. However, the diagnostic yield of whole exome sequencing remained at similar levels during the early-NGS period at 54.5% and in the NGS era at 59%. ConclusionsThe more genetic ESD (27.4%) was defined for IESS in the NGS era with the implication of precision therapy (37.7%).

P150 Diagnostic utility of anti-cN1A autoantibody testing in sporadic inclusion body myositis

Abstract Background/Aims Sporadic inclusion body myositis (sIBM) is the most common acquired myopathy in patients aged over 50 years. Diagnostic criteria encompass clinical, biochemical, and myopathological features. Certain myopathological features possess high specificity but low sensitivity; reliance on such findings may lead to delayed or misdiagnoses. The discovery of autoantibodies against cytosolic 5'-Nucleotidase 1A (cN1A) in sIBM patients suggests an autoimmune component in pathogenesis, but the inclusion of this autoantibody in diagnostic criteria remains uncertain. Additionally, optimal testing methodology has not been established, with varying techniques (e.g., ELISA/line-blot) in use. We assessed antibody profiles in an sIBM cohort and reviewed diagnoses in anti-cN1A positive patients. Methods This study was based at the Northern Care Alliance NHS Foundation Trust which hosts a tertiary neuromuscular referral service for the North-West of England. Data sources included myositis clinic and immunology results databases. All patients tested using a validated myositis line-blot immunoassay (EUROLINE 16 Antigen et cN1A [EUROIMMUN]) November 2021-April 2023 were included. Diagnoses of all tested patients were identified through case-note review. Sensitivity and specificity metrics were calculated based on diagnosis and anti-cN1A antibody status. Results The total number of patients tested for anti-cN1A was 495. Of these, 10 patients had a diagnosis of sIBM. The true-positive and false-negative rates were both 50% (n = 5 each). Of the 485 patients who did not have sIBM, true-negativity was 97.52% (n = 473) and false-positivity 2.47% (n = 12). Overall, anti-cN1A had a sensitivity of 50%, specificity of 97.52%, positive predictive value of 29.41% and negative predictive value of 98.95% for sIBM (Table 1). Patients with a false-positive anti-cN1A antibody had diagnoses of: primary Raynaud’s (n = 5); undifferentiated CTD (n = 3); systemic sclerosis (n = 2); non-sIBM myositis (n = 2). Conclusion Anti-cN1A detected using the EUROLINE 16 Antigen assay has high specificity but lacks sensitivity for sIBM, consistent with previous literature. These findings suggest that this assay performs similarly to other cN1A detection methodologies and has utility in confirming the diagnosis of sIBM where there is clinical suspicion. Further real-world analysis of antibody data in larger cohorts is required to clarify the role of serological testing in sIBM diagnostic criteria, to improve diagnostic delays and misclassifications. Disclosure M. Al-Attar: None. T. Khoo: None. J.B. Lilleker: None. H. Chinoy: None.

1101 Long-term Trends in Utilization of Sleep Diagnostic Tests Among Medicare Beneficiaries

1101 Long-term Trends in Utilization of Sleep Diagnostic Tests Among Medicare Beneficiaries

Diagnostic Utility of MOG Antibody Testing in Cerebrospinal Fluid.

The aim of this study was to assess the diagnostic utility of cerebrospinal fluid (CSF) myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) testing. We retrospectively identified patients for CSF MOG-IgG testing from January 1, 1996, to May 1, 2023, at Mayo Clinic and other medical centers that sent CSF MOG-IgG for testing including: controls, 282; serum MOG-IgG positive MOG antibody-associated disease (MOGAD), 74; serum MOG-IgG negative high-risk phenotypes, 73; serum false positive MOG-IgG with alternative diagnoses, 18. A live cell-based assay assessed CSF MOG-IgG positivity (IgG-binding-index [IBI], ≥2.5) using multiple anti-human secondary antibodies and end-titers were calculated if sufficient sample volume. Correlation of CSF MOG-IgG IBI and titer was assessed. The pan-IgG Fc-specific secondary was optimal, yielding CSF MOG-IgG sensitivity of 90% and specificity of 98% (Youden's index 0.88). CSF MOG-IgG was positive in: 4/282 (1.4%) controls; 66/74 (89%) serum MOG-IgG positive MOGAD patients; and 9/73 (12%) serum MOG-IgG negative patients with high-risk phenotypes. Serum negative but CSF positive MOG-IgG accounted for 9/83 (11%) MOGAD patients, and all fulfilled 2023 MOGAD diagnostic criteria. Subgroup analysis of serum MOG-IgG low-positives revealed CSF MOG-IgG positivity more in MOGAD (13/16[81%]) than other diseases with false positive serum MOG-IgG (3/15[20%]) (p = 0.01). CSF MOG-IgG IBI and CSF MOG-IgG titer (both available in 29 samples) were correlated (Spearman's r = 0.64, p < 0.001). CSF MOG-IgG testing has diagnostic utility in patients with a suspicious phenotype but negative serum MOG-IgG, and those with low positive serum MOG-IgG results and diagnostic uncertainty. These findings support a role for CSF MOG-IgG testing in the appropriate clinical setting. ANN NEUROL 2024;96:34-45.

Diagnostic Utility of QuantiFERON-Gold Testing in Patients with Ocular Inflammation in a Low-Endemic Tuberculosis Region

PurposeTo evaluate the diagnostic value of QuantiFERON Gold (QFT-G) testing for ocular inflammation in a low prevalence tuberculosis (TB) area. DesignDiagnostic utility analysis. MethodsA review was performed for all uveitis patients who underwent QFT-G testing at the University of Colorado Eye Center from 2009-2022. Records were reviewed to assess QFT-G positivity rate and to identify which patients were tested for diagnostic purposes, defined as meeting the Standardization of Uveitis Nomenclature (SUN) criteria for tubercular uveitis (TBU): anterior uveitis with iris nodules, serpiginous-like choroiditis, choroidal nodule resembling a tuberculoma, multifocal choroiditis, or occlusive retinal vasculitis. ResultsA total of 388 patients with uveitis underwent QFT-G testing, of which 17 (4.38%) were positive. Only one (5.88%) patient had true TBU with anterior uveitis with iris nodules. The remaining 16 (94.1%) patients did not meet SUN criteria for TBU and were incidentally found to be QFT-G positive during laboratory work-up prior to immunosuppression. The positive predictive value was 100% when QFT-G testing was performed in patients who met SUN criteria for TBU, whereas the positive predictive value was 0% for QFT-G testing performed in patients who did not meet SUN criteria for TBU. ConclusionIn low prevalence areas, the majority of QFT-G positive tests in uveitis patients are coincidental and unrelated to their uveitic disease process. The diagnostic value of a TB test is likely to be minimal unless the SUN clinical criteria for tubercular uveitis are met.

Diagnostic yield from cardiac gene testing for inherited cardiac conditions and re-evaluation of pre-ACMG variants of uncertain significance.

Inherited cardiomyopathies (HCM, DCM, ACM) and cardiac ion channelopathies (long QT/Brugada syndromes, CPVT) are associated with significant morbidity and mortality; however, diagnosis of a familial pathogenic variant in a proband allows for subsequent cascade screening of their at-risk relatives. We investigated the diagnostic yield from cardiac gene panel testing and reviewed variants of uncertain significance from patients attending three specialist cardiogenetics services in Ireland in the years 2002 to 2020. Reviewing molecular genetic diagnostic reports of 834 patients from 820 families, the initial diagnostic yield of pathogenic/likely pathogenic variants was 237/834 patients (28.4%), increasing to 276/834 patients (33.1%) following re-evaluation of cases with variant(s) of uncertain significance. Altogether, 42/85 patients with VUS reviewed (49.4%) had a re-classification that could change their clinical management. Females were more likely to carry pathogenic/likely pathogenic variants than males (139/374, 37.2% vs 137/460, 29.8%, respectively, p = 0.03), and the diagnostic yields were highest in the 0 to < 2 years age group (6/12, 50.0%) and amongst those tested for cardiomyopathy gene panels (13/35, 37.1%). Variants in the MYBPC3/MYH7 (87/109, 79.8%) and KCNQ1/KCNH2 (91/100, 91.0%) genes were the predominant genetic causes for hypertrophic cardiomyopathy and long QT syndrome, respectively. Our study highlights the importance of collation and review of pre-ACMG genetic variants to increase diagnostic utility of genetic testing for inherited heart disease. Almost half of patients with pre-ACMG VUS reviewed had their variant re-classified to likely pathogenic/likely benign which resulted in a positive clinical impact for patients and their families.