Diagnostic Accuracy Research Articles

Association of CSF α-Synuclein Seeding Amplification Assay Results With Clinical Features of Possible and Probable Dementia With Lewy Bodies.

The clinical diagnosis of dementia with Lewy bodies (DLB) depends on identifying significant cognitive decline accompanied by core features of parkinsonism, visual hallucinations, cognitive fluctuations, and REM sleep behavior disorder (RBD). Hyposmia is one of the several supportive features. α-Synuclein seeding amplification assays (αSyn-SAAs) may enhance diagnostic accuracy by detecting pathologic αSyn seeds in CSF. In this study, we examine how different clinical features associate with CSF αSyn-SAA positivity in a large group of clinically diagnosed participants with DLB. Cross-sectional and longitudinal CSF samples from the multicentered observational cohort study of the DLB Consortium and similar studies within the Parkinson's Disease Biomarker Program, contributed by academic medical centers in the United States, underwent αSyn-SAA testing. Participants included those clinically diagnosed with DLB and 2 control cohorts. Associations between core DLB features and olfaction with αSyn-SAA positivity were evaluated using logistic regression. CSF samples from 191 participants diagnosed with DLB (mean age 69.9 ± 6.8, 15% female), 50 age-matched and sex-matched clinical control participants, and 49 younger analytical control participants were analyzed. Seventy-two percent (137/191) of participants with DLB had positive αSyn-SAAs vs 4% of the control groups. Among participants with DLB, those who were αSyn-SAA-positive had lower Montreal Cognitive Assessment scores (18.8 ± 5.7 vs 21.2 ± 5.2, p = 0.01), had worse parkinsonism on the Movement Disorders Society Unified Parkinson's Disease Rating Scale part III (33.8 ± 15.1 vs 25.6 ± 16.4, p = 0.001), were more likely to report RBD (114/133 [86%] vs 33/53 [62%], p < 0.0001), and had worse hyposmia on the University of Pennsylvania Smell Identification Test (UPSIT) (94/105 [90%] below 15th percentile vs 14/44 [32%], p < 0.0001). UPSIT percentile had the highest area under the curve (0.87, 95% CI 0.81-0.94) in predicting αSyn-SAA positivity and participants scoring at or below the 15th percentile of age and sex normative values had 18.3 times higher odds (95% CI 7.52-44.6) of having a positive αSyn-SAA test. Among 82 participants with longitudinal CSF samples, 81 (99%) had the same αSyn-SAA result for initial and follow-up specimens. A substantial proportion of clinically diagnosed participants with DLB had negative αSyn-SAA results. Hyposmia was the strongest clinical predictor of αSyn-SAA positivity. Hyposmia and αSyn-SAA may have utility in improving the diagnostic assessment of individuals with potential DLB. This study provided Class III evidence that CSF αSyn-SAA distinguishes patients with clinically diagnosed DLB from normal controls.

Blood Astrocyte Biomarkers in Alzheimer Disease: A Systematic Review and Meta-Analysis.

Neuroinflammation, particularly early astrocyte reactivity, is a significant driver of Alzheimer disease (AD) pathogenesis. It is unclear how the levels of astrocyte biomarkers change in patients across the AD continuum and which best reflect AD-related change. We performed a systematic review and meta-analysis of 3 blood astrocyte biomarkers (glial fibrillary acidic protein [GFAP], chitinase-3-like protein 1 [YKL-40], and S100B) in patients clinically diagnosed with AD. MEDLINE and Web of Science were searched on March 23, 2023, without restrictions on language, time, or study design, for studies reporting blood levels of the astrocyte biomarkers GFAP, YKL-40, or S100B in patients on the AD continuum (including those with mild cognitive impairment [MCI] and dementia) and a cognitively unimpaired (CU) control population. AD diagnosis was based on established diagnostic criteria and/or comprehensive multidisciplinary clinical consensus. Studies reporting indirect biomarker measures (e.g., levels of biomarker autoantibodies) were excluded. Risk of bias assessment was performed using the revised Quality Assessment of Diagnostic Accuracy Studies tool. Pooled effect sizes were determined using the Hedge g method with a random-effects model. The review was prospectively registered on PROSPERO (registration number CRD42023458305). The search identified 1,186 studies; 36 met inclusion criteria (AD continuum n = 3,366, CU n = 4,115). No study was assessed to have a high risk of bias. Compared with CU individuals, patients on the AD continuum had higher GFAP and YKL-40 levels (GFAP effect size 1.15, 95% CI 0.94-1.36, p < 0.0001; YKL-40 effect size 0.38, 95% CI 0.28-0.49, p < 0.0001). Both biomarkers were elevated in more advanced clinical stages of the disease (i.e., in AD dementia compared with MCI due to AD: GFAP effect size 0.48, 95% CI 0.19-0.76, p = 0.0009; YKL-40 effect size 0.34, 95% CI 0.10-0.57, p = 0.0048). No significant differences in blood S100B levels were identified. We demonstrated significant elevations in blood GFAP and YKL-40 levels in patients on the AD continuum compared with CU individuals. Furthermore, within the AD clinical spectrum, significant elevation correlated with more advanced disease stage. Our findings suggest that both biomarkers reflect AD-related pathology. Our findings are limited by the lack of cultural and linguistic diversity in the study populations meta-analyzed. Future meta-analyses using a biomarker-defined AD population are warranted.

Chinese expert consensus on the pathological diagnosis of interstitial lung disease with transbronchial lung cryobiopsy specimens

Transbronchial lung cryobiopsy (TBLC) is an applicable technique that can provide a histologic diagnosis of interstitial lung disease(ILD). The general sample size of TBLC is much smaller than that of surgical lung biopsy (SLB), which raises more concerns about the procedure's diagnostic accuracy. A guiding consensus and guidelines on the pathological procedure of ILD with TBLC are required to better guide pathologists in diagnostic practice. The Respiratory Pathology Working Group of the Respiratory Physicians Branch of the Chinese Medical Doctor Association and the Thoracic Diseases Group of the Pathological Branch of the Chinese Medical Association, jointly organized by experts, have worked together to discuss and formulated the consensus. The consensus is based on literature review, clinical practice, collection of clinical issues, and discussion during a series of meetings. Experts approved the final proposed consensus with more than 70% of votes in favor (Delphi). The consensus summarized the delivery requirements, quality evaluation and artificial phenomena of TBLC specimens. It also proposed the diagnostic principles and procedures, types of ILD corresponding to major pathological changes, and major corresponding differential diagnoses of TBLC specimens. Finally, the consensus formed 14 recommendations for clinical diagnosis and multidisciplinary discussion.The recommendations are addressed as follows.Recommendation 1: We suggest that the TBLC clinical manipulators should observe and measure the size of the specimen in time. The specimen size should be greater than 5 mm in diameter, and multiple pieces(3 to 5 pieces)are recommended.Recommendation 2: Pathologists should record the number of blocks of tissue submitted for examination and the volume, color, and texture of each specimen. Evaluation of the proportion of alveolar parenchyma/airway components under the microscope, analysis of the type and distribution of lesions will facilitate making diagnostic suggestions.Recommendation 3: The size of TBLC specimens is significantly smaller than SLB and may not show sufficient features of ILD or secondary changes. It is more necessary to combine the evaluation of clinical changes and lesion distribution assessed by HRCT for a comprehensive diagnosis.Recommendation 4: Common microscopic artefacts of TBLC specimen are mass of red blood cells, proteinaceous fluid and fibrin exudation. In the absence of hemosiderin cells or clinical signs of hemoptysis symptoms, the diagnosis of pulmonary hemorrhagic disease should be considered with caution.Recommendation 5: TBLC is not a suggested diagnosis when the pathological changes are mainly located in the pleural or subpleural lung tissues, e.g., pleuroparenchymal fibroelastosis.Recommendation 6: The principle of pathological diagnosis of ILD in TBLC is consistent with SLB, with a description of the main pathological morphological change and a tendentious pathological diagnosis; if the lesion is not fully shown, only a pathological description is given.Recommendation 7: A well-sampled TBLC specimen may show patchy fibrosis and fibroblast foci in UIP, supporting a pathological diagnosis of a probable UIP pattern. TBLC may not display sufficient features of the distribution of subpleural and peripheral lung lesions in UIP, as well as secondary lesions.Recommendation 8: TBLC specimens show diffuse inflammation and fibrosis with well-preserved lung tissue structure, which may support a pathological diagnosis of NSIP; if the distribution of lesions and lung tissue structure are difficult to evaluate, it is recommended that a pathological diagnosis of fibrotic ILD or cellular ILD be made.Recommendation 9: TBLC specimens may show pathological features of NSIP accompanied by organization, but it is difficult to accurately evaluate the proportion of organization area. In this scenario, a descriptive diagnosis of NSIP accompanied by organization is suggested.Recommendation 10: It is recommended to diagnose organizing pneumonia if only distal airway organization is present in TBLC; in addition to organization, if pathological histology is accompanied by obvious interstitial fibrosis and lung tissue remodelling, granuloma formation, obvious neutrophil infiltration or accompanied with abscess formation, obvious eosinophil infiltration, tissue necrosis, hyaline membrane formation or vasculitis, secondary OP should be considered.Recommendation 11: It is recommended to diagnose acute fibrinous and organizing pneumonia (AFOP) if lesions on TBLC show features of organizing pneumonia and fibrin balls.Recommendation 12: A diagnosis of smoking-related ILD (RB-ILD or DIP) is suggested when a good sampling of TBLC shows a significant accumulation of histocytes or smoker's macrophages in the alveolar spaces, and without specific changes sufficient for other diagnoses. If the lesions are confined to the lumen of respiratory bronchioles and the immediate peribronchiolar airspaces, RB-ILD is supported; if the distribution is diffuse, DIP should be considered. If it is difficult to determine the distribution of the lesions, it is necessary to integrate clinical and chest CT imaging findings to differentiate RB-ILD from DIP.Recommendation 13: A well-sampled TBLC specimen can display the pathological features of DAD and then also support such a pathological diagnosis.Recommendation 14: Lymphoid interstitial pneumonia (LIP) should show diffuse lymphocyte infiltration and lymphoid follicle formation in the lung interstitium in TBLC specimens. It is recommended that chest CT imaging be combined to determine whether the lesion is diffuse to differentiate from other lymphoproliferative diseases.

Diagnosis of peripheral cavitary squamous cell lung carcinoma with Aspergillus infection using LungPro navigation system: a case report

Virtual bronchoscopic navigation (VBN) is increasingly being used to diagnose peripheral lung lesions, allowing precise guidance of the bronchoscope to the target lesions, thereby improving diagnostic accuracy. This paper reported a patient admitted due to hemoptysis, with an initial clinical diagnosis of squamous cell lung carcinoma with brain and bone metastases. Previous attempts had failed to obtain tissue samples from the lung lesions. Upon admission, the LungPro navigation system was used to perform a bronchoscopic transparenchymal nodule access (BTPNA). Pathological examination of the lung tissue and microbiological analysis of bronchoalveolar lavage fluid confirmed the diagnosis of peripheral cavitary squamous cell lung carcinoma with Aspergillus infection. Following antifungal and antineoplastic treatment, the patient's symptoms improved markedly and she was subsequently discharged.

Siderophore-Conjugated Antifungals: A Strategy to Potentially Cure Fungal Infections.

Fungi pose a global threat to humankind due to the increasing emergence of multi-drug-resistant fungi. There is a rising incidence of invasive fungal infections. Due to the structural complexity of fungal cell membranes, only a few classes of antifungal agents are effective and have been approved by the U.S. FDA. Hence, researchers globally are focusing on developing novel strategies to cure fungal infections. One of the potential strategies is the "Trojan horse" approach, which uses the siderophore-mediated iron acquisition (SIA) system to scavenge iron to deliver potent antifungal agents for therapeutics and diagnostics. These siderophore conjugates chelate to iron and are taken up through siderophore-iron transporters, which are overexpressed exclusively on microbes such as bacteria or fungi, but not mammalian cells. Our comprehensive review delves into recent advancements in the design of siderophore-conjugated antifungal agents to gain fungal cell entry. Notably, our focus extends to unraveling the intricate relationship between the structure of natural siderophores or siderophore-like molecules and the resulting antifungal activity. By exploring these design strategies, we aim to contribute to the ongoing discourse on combating drug-resistant fungal infections and advancing the landscape of antifungal theranostics.

Значение видео-уродинамического исследования в выборе метода лечения детей с нейрогенными дисфункциями мочевого пузыря

Video urodynamics is the standard for assessment of the lower urinary tract in children with neurogenic urinary disorders aiming to provide more information about the condition of the lower urinary tract v. retrograde urethrocystography. Video urodynamics parameters are used as possible indicators for choosing various surgical treatment options, however, all work is focused on adult patients, and data for the pediatric cohort were not available as yet. The purpose of this research was the evaluation of the role of video urodynamics and retrograde urethrocystography in the selection of effective conservative and surgical treatment of neurogenic urinary disorders in children. Materials and methods used: 112 patients aged 1,8 to 18 y/o with neurogenic urinary disorders were included in the study, of whom 101 were those who had been proven effectively treated with conservative M-cholinoblockers or had successfully undergone minimally invasive surgery as follows: intradetrusor injection of botulinum toxin (n=21), transurethral correction of VUR (n=17), simultaneous execution of two of these interventions (n=22). Based on the results of video urodynamic and cystographic examination of these patients with the CHAID technique, the classification trees were built in order to evaluate the effective treatment (conservative/surgical). Results: the median age of patients was 9,0 years [7,8-12,0]. The first classification tree containing the parameter “presence of VUR according to the results of retrograde cystography.” The sensitivity of the obtained model for the effectiveness of surgical treatment was 83,3% v. 73,2% for conservative treatment. The accuracy was 79,2%. The ROC-AUC value was 0,783. The second classification tree contained the maximum Pves value according to the results of the video urodynamics, presence of hyperactivity, presence of VUR. The sensitivity of the obtained model for the effectiveness of surgical treatment was 93,3% v. 97,6% for conservative treatment. The accuracy was 95,0%. The ROC-AUC value was 0,972. Comparison of ROC-AUC values by the Delong test revealed statistically significant differences between these binary classification metrics (p&lt;0.001). Conclusion: the parameters of video urodynamics have greater diagnostic accuracy in effective prediction of both conservative and surgical treatment methods compared to the retrograde urethrocystography.

РАСПРОСТРАНЕННОСТЬ И КЛИНИЧЕСКИЕ ОСОБЕННОСТИ ВОДОРОДНО –МЕТАНОВОГО ВАРИАНТА ТЕЧЕНИЯ СИНДРОМА ИЗБЫТОЧНОГО БАКТЕРИАЛЬНОГО РОСТА У ДЕТЕЙ С ФУНКЦИОНАЛЬНОЙ ДИСПЕПСИЕЙ

Prevalence of small intestinal bacterial overgrowth (SIBO) syndrome, improved diagnostic accuracy and therapeutic approaches require further study. The purpose of this research was to evaluate the effect of hydrogen dominant or hydrogen-producing SIBO (H-SIBO) and methane dominant or methane-producing SIBO (M-SIBO) types on the severity of clinical manifestations in children with functional dyspepsia (FD). Materials and methods used: a single-center cross-sectional study of 90 pediatric patients: 41 (45.6%) aged 11.0 [9.0:13.0] y/o with FD, of which 20 (48.8%) girls/21 (51.2%) boys, and 49 (54.4%) evaluatively healthy children (“control group”) aged 12.0 [9.5:13.6] y/o, of whom 27 (55.1%) girls/22 (44.9%) boys. The SIBO was determined with the domestically-produced “Lactophan” hydrogen breathing test by AMA Co., Ltd. (Saint Petersburg, Russia) and the “GastroCH4ECK Gastrolyzer” CH4 &amp; H2 monitor by Bedfont Scientific Ltd. (Harrietsham, Maidstone, Kent, England, UK). Results: SIBO (41/100% and 28/57.1%, p&lt;0.001) and H-SIBO (29/70.7% and 18/36.7%, p=0.045) were statistically significantly more often detected in children with FD than in the control group. The M-SIBO incidence (12/29.3% and 10/20.4%, p=0.467) did not differ statistically significantly between the groups. The methane output at the 60th to 90th minutes of the breathing test was 1.7 to 1.8 times higher in FD patients. The hydrogen threshold values at the 60th minute of the breathing test in FD patients for predicting of complaints were as follows: above 35 ppm (ROC-AUC=0.88, 95% CI=0.61-1.00, SE 87.5%, SP 97.2%) for “Sour taste in the mouth,” and above 33 ppm (ROC-AUC=0.80, 95% CI=0.53-1.00, SE 80.6%, SP 75.0%) for “Diarrhea.” The hydrogen threshold value at the 90th minute of the breathing test for “Flatulence” symptom was 44 ppm (ROC-AUC=0.71, 95% CI=0.36-0.88, SE 60.9%, SP 75.0%). Conclusion: testing for methane had increased the accuracy of SIBO diagnosis by 29.3% in patients with FD, i.e. from 70.7% to 100%! The relationship between the hydrogen and the methane concentrations coupled with the presence of dyspeptic symptoms may require the correction of SIBO in patients with FD.

Current Status of Magnetic Resonance Imaging Use in Bladder Cancer.

Bladder cancer (BC) is a significant global health concern, with over 500,000 new cases and 200,000 deaths annually, emphasizing the need for accurate staging and effective management. Traditional diagnostic techniques, such as cystoscopy and transurethral resection, are fundamental but have limitations in accurately assessing the depth of invasion. These limitations include the possibility of understaging and procedural variability, which can significantly impact treatment decisions. This review focuses on the role of multiparametric magnetic resonance imaging (mpMRI) in the diagnosis and staging of BC, particularly emphasizing the Vesical Imaging-Reporting and Data System (VI-RADS) framework. By enhancing interpretive consistency and diagnostic accuracy, mpMRI and VI-RADS offer detailed visualization of tumor characteristics and depth of invasion, while reducing the need for more invasive traditional methods. These advancements not only improve staging accuracy but also enhance treatment planning, underscoring the importance of advanced imaging in evolving BC management and positively influencing patient outcomes.

Minimum Fascia-Tumour Distance for Differentiating Deep Lobe From Superficial Lobe Benign Parotid Tumours: A Retrospective Study and Meta-Analysis.

This study was designed to evaluate the diagnostic efficacy of the minimum fascia-tumour distance (MFTD) in distinguishing deep-lobe benign parotid tumours from superficial-lobe tumours through both an original study and a meta-analysis. In this study, we performed a retrospective analysis of data from 91 patients who had been diagnosed with benign parotid tumours. The MFTD values were sourced from preoperative ultrasound examinations. The locations of these tumours were confirmed through surgical findings. We assessed the diagnostic accuracy of MFTD by utilising receiver operating characteristic (ROC) curves. Additionally, we conducted a systematic review of the pertinent literature and performed a diagnostic meta-analysis to ascertain the overall diagnostic efficacy of MFTD in identifying benign parotid tumours. Patients with tumours in the deep lobe had a significantly greater MFTD than patients with tumours in the superficial lobe. Using a cutoff value of 3.50 mm for MFTD, we found an AUC of 0.93, a sensitivity of 81.8%, and a specificity of 98.8%. Our meta-analysis included seven studies covering a total of 1689 tumours. The pooled values for sensitivity, specificity, and diagnostic odds ratio (OR) of MFTD were 81.0%, 89.0%, and 32.2, respectively. The AUC of the summarised ROC curve of MFTD was 0.90. The MFTD demonstrated reliable diagnostic accuracy in identifying deep-lobe benign parotid tumours and may be incorporated into standard evaluations before parotidectomy.

The undervalued league of insulin resistance testing: uncovering their importance.

Type 2 diabetes, obesity, and several other metabolic diseases are all largely attributed to the problem known as insulin resistance. Diagnosing insulin resistance promptly and accurately is essential for adequately managing and intervening in metabolic disorders. Several diagnostic methods have been developed to assess insulin resistance. However, each method has advantages and disadvantages. The most precise test is the hyperinsulinemic-euglycemic clamp, which examines the direct impact of insulin on glucose uptake by tissues. However, it is primarily utilized in research due to its complexity and intrusiveness. Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and the Quantitative Insulin Sensitivity Check Index (QUICKI) are the second most used Insulin resistance tests in the clinical setup. These tests are based on measuring the fasting glucose and insulin levels. The Oral Glucose Tolerance Test (OGTT), Insulin tolerance test, and the Matsuda Index are further diagnostic procedures that shed light on insulin sensitivity. The improved techniques, such as the insulin suppression test and the minimal model analysis, provide substitutes for unique clinical circumstances. Additionally, including extra measurements with these tests, like waist circumference, lipid profiles, and inflammatory markers, can improve the evaluation of insulin resistance. In summary, identifying insulin resistance is essential for the early detection and treatment of various metabolic illnesses. To make educated judgments and improve patient care, healthcare workers should be aware of thedifferent available diagnostic tests and how they are used in each situation. Insulin resistance detection and monitoring will require further study to improve current diagnostic approaches and create novel, less invasive techniques.

Analytical interference in CA 19-9 immunoassay generates false-positive results in a young woman with a low-grade appendiceal tumor: An educational case report and brief literature review.

CA 19-9 (carbohydrate antigen 19-9) is a tumor marker widely used for the follow-up of patients with pancreatic cancer and other digestive neoplasia. This case report describes a discrepancy between the results of serum CA 19-9 analyses using the Alinity analytical platform (Abbott™) and two other techniques, Kryptor Gold (ThermoFisher Scientific™) and Cobas E411 (Roche™), in the context of a young woman with appendiceal mucocele. In this context, when the serum concentration of CA 19-9 is high, it may raise concerns about potential malignancy or rupture of the mucocele that may lead to tumoral dissemination in the abdominal cavity. In the present case, we observed with Alinity a false elevation in CA 19-9 concentration at 190 kU/L (normal range<37 kU/L) before appendix resection that continued to increase until reaching 619 kU/L six months after surgery. This situation led to unnecessary additional tests, increased hospitalization time and stress for the patient who also had to interrupt her medically assisted reproduction project. We solved this case using new measurements in CA 19-9 concentration with two other techniques, Kryptor Gold and Cobas E411, and we identified an analytical interference caused by the presence of heterophile antibodies. In all cases, abnormal result initially obtained with Alinity was found below normal range not only with the two other techniques but also with Alinity after a neutralisation step by using Heterophile Blocking Tubes (Scantibodies Laboratory™). Analytical interferences in medical tests can lead to inappropriate medical care. It is an important issue requiring a continuing training of biologists who must be aware of these problems, which are recurring concerns and are not always easy to identify in laboratories of medical biology, in particular when immunoassays are used. This case report also provides an opportunity to do a brief review of the literature and to remind some recommendations and actions to take into consideration in the presence of discrepancies between the clinic and the biology, in particular, one of them is to measure the biological analyte with a different technique. Moreover, the use of Heterophile Blocking Tubes neutralizing specifically the heterophile antibodies may be useful. In all cases, dialogue between clinicians and biologists remains essential.

Cervical Auscultation for Detecting Oropharyngeal Aspiration in Paediatric and Adult Populations: A Systematic Review and Meta-Analysis.

Cervical auscultation (CA) involves listening to swallowing and respiratory sounds and/or vibrations to detect oropharyngeal aspiration (OPA). CA has shown promising diagnostic test accuracy when used with the clinical swallowing examination and is gaining popularity in clinical practise. There has not been a review to date analysing the accuracy of CA in paediatric and adult populations with meta-analyses. To determine the accuracy of CA in detecting OPA in paediatric and adult populations, when compared to instrumental assessments. Databases searched included MEDLINE, PubMed, Embase, CINAHL, AustHealth, Cochrane and Web of Science. The search was restricted between 01 October 2012 and 01 October 2022. Inclusion criteria included (a) all clinical populations of all ages, (b) who have had an instrumental assessment and (c) CA. All study types were included. Studies were reviewed independently by two authors. The methodological quality of the studies was analysed using the QUADAS-2. Ten studies met the inclusion criteria for this review and meta-analyses. The pooled diagnostic performance of CA in detecting OPA was 0.91 for sensitivity and 0.79 for specificity. The area under the curve summary receiver operating curve (sROC) was estimated to be 0.86, thereby indicating good discrimination of OPA. Most studies scored high for risk of bias in at least one domain in the QUADAS-2, likely attributed to a lack of high-quality prospectively designed studies. There are promising diagnostic test accuracies for the use of CA in detection of OPA. Future research could include using CA in specific clinical populations and settings, and identifying standardised criteria for CA.

Evaluation of truenat assays for the diagnosis of pulmonary and extrapulmonary tuberculosis: a systematic review and meta-analysis.

Tuberculosis (TB) remains a significant global health concern, necessitating accurate and timely diagnostic methods. This study aimed to conduct a systematic review and meta-analysis to assess the diagnostic accuracy of Truenat assays for both pulmonary TB (PTB) and extrapulmonary TB (EPTB). PubMed, Scopus, and Web of Science were systematically searched for studies comparing Truenat assays to Mycobacterium tuberculosis confirmation methods. Comparing Truenat MTB assay with Lowenstein-Jensen (LJ) culture, the pooled sensitivity and specificity were 86% (95% CI: 79-91%) and 86% (95% CI: 82-90%), respectively. For Mycobacterial Growth Indicator Tube (MGIT) culture comparison, pooled sensitivity was 88% (95% CI: 82-92%) with a specificity of 79% (95% CI: 57-92%). Compared to smear microscopy, Truenat assays displayed the pooled sensitivity and specificity of 92% (95% CI: 78-98%) and 86% (95% CI: 64-95%). In comparison to Xpert MTB/RIF, Truenat assays exhibited a pooled sensitivity of 92% (95% CI: 80-97%) and a pooled specificity of 92% (95% CI: 56-99%) for PTB detection, and a pooled sensitivity of 94% (95% CI: 81-98%) and a specificity of 77% (95% CI: 32-96%) for the diagnosis of EPTB. This study underscores the potential of Truenat assays as valuable tools for diagnosing both PTB and EPTB. CRD42024526686.

Global Study on the Accuracy of Human Epidermal Growth Factor Receptor 2-Low Diagnosis in Breast Cancer.

Recently, a new type of antibody-drug conjugate, trastuzumab-deruxtecan (T-DXd), has been approved for the treatment of metastatic breast cancer with low level of human epidermal growth factor receptor 2 (HER2) gene expression. Thereby, eligibility relies on an accurate diagnosis of HER2-low status defined by immunohistochemistry IHC 1+/2+ with no gene amplification. To assess pathologists' accuracy and training efficacy in the diagnosis of HER2-low. Agreement rates of HER2-low scoring in breast cancer tissue were assessed between expert consensus and real-world pathologists (n = 77 from 14 countries) before and after a specific 4-hour training for HER2-low detection. Two assays were evaluated, the Ventana Pathway 4B5 CDx and the Dako HercepTest (polyclonal). Concordance of the pathologists with consensus score and efficacy of training were measured by Cohen κ, overall rater agreement, and receiver operating characteristic (ROC) curve statistics. In the Ventana 4B5 HER2-low category, baseline agreement rates were >80% but <90%. Negative percentage agreement was improved from 80.6% to 91.1% by training. In the HER2-0 category, positive percentage agreement (74.6%) was the only parameter below the 80% benchmark but was significantly improved to 89.2% after training. Training efficacy was confirmed by ROC curve analysis, which shows improvement for the identification of HER2-0 and HER2-low cases. Finally, in-depth examination of cases with discordant HER2 status disclosed specific issues of HER2-low underscoring and overscoring. The ability of pathologists to achieve acceptable diagnostic accuracy in identifying patients with HER2-low breast cancer could be enhanced by short-term training. Potential routes to improve the quality of HER2-low scoring in clinical practice have been identified.

Applications of artificial intelligence to myeloproliferative neoplasms: a narrative review.

Artificial intelligence (AI) is a rapidly growing field of computational research with the potential to extract nuanced biomarkers for the prediction of outcomes of interest. AI implementations for the prediction for clinical outcomes for myeloproliferative neoplasms (MPNs) are currently under investigation. In this narrative review, we discuss the AI investigations for the improvement of MPN clinical care utilizing either clinically available data or experimental laboratory findings. Abstracts and manuscripts were identified upon querying PubMed and the American Society of Hematology conference between 2000 and 2023. Overall, multidisciplinary researchers have developed AI methods in MPNs attempting to improve diagnostic accuracy, risk prediction, therapy selection, or pre-clinical investigations to identify candidate molecules as novel therapeutic agents. It is our expert opinion that AI methods in MPN care and hematology will continue to grow with increasing clinical utility. We believe that AI models will assist healthcare workers as clinical decision support tools if appropriately developed with AI-specific regulatory guidelines. Though the reported findings in this review are early investigations for AI in MPNs, the collective work developed by the research community provides a promising framework for improving decision making in the future of MPN clinical care.

Pitfalls in the Cytological Diagnosis of Nodal Hodgkin Lymphoma.

Hodgkin lymphoma (HL) is a hematopoietic neoplasm characterized by malignant Reed-Sternberg (RS) cells in an inflammatory background. Although the cytological features of HL are well elucidated in literature, yet many postulated factors cause its misdiagnosis. This study aims to assess the diagnostic reliability of fine needle aspiration cytology (FNAC) in HL and evaluate the factors contributing to a false-negative and false-positive diagnosis, taking histopathology as the gold standard. This was a retrospective study in which 47 cases of HL diagnosed on histopathology were compared with their prior cytological diagnosis. The patient's age ranged from 3 to 80 years (median: 36 years) with a M:F ratio of 2.9:1. Lymph node aspirations were performed from multiple anatomical sites, out of which the cervical was the most common (57.8%). FNAC was inconclusive in two cases due to unsatisfactory smears. The false-negative diagnosis of reactive lymphadenitis was given in four cases, and false-positive in four cases, which included three cases of non-HL, and one case of malignant small round blue cell tumor. The overall diagnostic accuracy of FNAC in the diagnosis of HL was 82.2%. The cytological diagnosis of HL can be challenging when classic RS cells are absent. Contributing factors for a false-negative diagnosis include obscuring reactive inflammatory cells, fibrosis of the involved lymph nodes, partial involvement of the lymph node, and misinterpretation. A thorough clinical examination with evaluation of FNAC smears from multiple areas, and ancillary tests help improve the diagnostic accuracy of cytological diagnosis.

Visualization and characterization of complement activation in acetylcholine receptor antibody seropositive myasthenia gravis.

There are no blood biomarkers to monitor treatment effects in myasthenia gravis (MG) or studies visualizing the acetylcholine receptor (AChR) antibody-induced membrane attack complex (MAC) at the human muscle membrane. This study aimed to compare levels of complement activation products and native complement components in MG patients and healthy controls (HCs) and to model the AChR antibody-mediated attacks in human muscle cells. We assessed the complement components and activation product levels with enzyme-linked immunosorbent assay and magnetic bead-based sandwich assays in plasma and sera of 23 MG patients and matched HCs. Receiver operator characteristic (ROC) curve analysis evaluated the diagnostic accuracy. Complement levels were correlated with the myasthenia gravis composite (MGC) scores. AChR+ MG modeling in human muscle cells used sera from nine MG patients and three HCs. MG patients had significantly higher plasma levels of C3a (p < .0001), C5 (p = .0003), and soluble C5b-9 (sC5b-9; p < .0001) than HCs. The ROC curve analysis showed a clear separation between MG patients and HCs for plasma C3a (AUC = 0.9720; p < .0001) and sC5b-9 (AUC = 0.8917, p < .0001). MG patients had higher levels of plasma complement Factor I (FI; p = .0002) and lower properdin levels (p < .0001). The MGC had moderate correlations with plasma Factor B (FB), FI, and Factor H. AChR+ MG patient sera triggered the deposition of MAC and reduced AChRs. We suggest validating plasma C3a and sC5b-9 as blood biomarkers for complement activation in MG. Further, the in vitro study allowed visualization of MAC deposition after applying AChR+ MG sera on human muscle cells.

Can clinicians identify community-acquired pneumonia on ultralow-dose CT? A diagnostic accuracy study

BackgroundWithout increasing radiation exposure, ultralow-dose computed tomography (CT) of the chest provides improved diagnostic accuracy of radiological pneumonia diagnosis compared to a chest radiograph. Yet, radiologist resources to rapidly report the chest CTs are limited. This study aimed to assess the diagnostic accuracy of emergency clinicians’ assessments of chest ultralow-dose CTs for community-acquired pneumonia using a radiologist’s assessments as reference standard.MethodsThis was a cross-sectional diagnostic accuracy study. Ten emergency department clinicians (five junior clinicians, five consultants) assessed chest ultralow-dose CTs from acutely hospitalised patients suspected of having community-acquired pneumonia. Before assessments, the clinicians attended a focused training course on assessing ultralow-dose CTs for pneumonia. The reference standard was the assessment by an experienced emergency department radiologist. Primary outcome was the presence or absence of pulmonary opacities consistent with community-acquired pneumonia. Sensitivity, specificity, and predictive values were calculated using generalised estimating equations.ResultsAll clinicians assessed 128 ultralow-dose CTs. The prevalence of findings consistent with community-acquired pneumonia was 56%. Seventy-eight percent of the clinicians’ CT assessments matched the reference assessment. Diagnostic accuracy estimates were: sensitivity = 83% (95%CI: 77–88), specificity = 70% (95%CI: 59–81), positive predictive value = 80% (95%CI: 74–84), negative predictive value = 78% (95%CI: 73–82).ConclusionThis study found that clinicians could assess chest ultralow-dose CTs for community-acquired pneumonia with high diagnostic accuracy. A higher level of clinical experience was not associated with better diagnostic accuracy.

Comparison of the modified Masood's scoring index versus international academy of cytology Yokohama system in the categorization of breast fine needle aspirates.

The Modified Masood Scoring Index (MMSI) categorizes breast fine needle aspirates into four categories non-proliferative breast diseases (PBD), PBD without atypia, PBD with atypia and carcinoma insitu/carcinoma. The International Academy of Cytology Yokohama System classifies the aspirates into five categories - inadequate, benign, atypical, suspicious, and malignant. Very few studies have been conducted so far to compare the diagnostic accuracy of this system. The objectives of the study were to classify breast fine needle aspirates according to the MMSI and IAC Yokohama and assess their risk of malignancy (ROM) and performance parameters. All breast FNAs received from June 2020 to May 2023 were classified according to the MMSI and IAC Yokohama. Using histopathological diagnosis as the gold standard, ROM and performance parameters were calculated. Out of the 559 breast fine needle aspirates, the histopathological correlation was available for 337 cases. The ROM for non-PBD, PBD without atypia, PBD with atypia and carcinoma insitu/carcinoma categories were 0%, 1.2%, 9.1% and 93%, respectively. The ROM for each of the categories of Yokohama system was 16.6%, 1.1%, 4.3%, 86.2% and 97.6%, respectively. The values for the sensitivity, specificity, PPV, NPV and diagnostic accuracy were slightly higher for IAC Yokohama (97.3%, 97.2%, 94.7%, 98.6% and 97.2%, respectively) than the MMSI (96.4%, 96.2%, 93%, 98.1% and 96.3%, respectively). Furthermore, another shortfall of MMSI is the inability to compare the Inadequate category of the Yokohama system. Overall Yokohama system proved to be a better system for categorizing breast lesions on FNAB as the scoring system provides more objective categorization and minimizes false positive and false negative cases.

Measuring the operational performance of an artificial intelligence-based blood tube-labeling robot, NESLI.

Laboratory testing, crucial for medical diagnosis, has 3 phases: preanalytical, analytical, and postanalytical. This study set out to demonstrate whether automating tube labeling through artificial intelligence (AI) support enhances efficiency, reduces errors, and improves outpatient phlebotomy services. The NESLI tube-labeling robot (Labenko Informatics), which uses AI models for tube selection and handling, was used for the experiments. The study evaluated the NESLI robot's operational performance, including labelling time, technical problems, tube handling success, and critical stock alerts. The robot's label readability was also tested on various laboratory devices. This research will contribute to the field's understanding of the potential impact of automated tube-labeling systems on laboratory processes in the preanalytical phase. NESLI demonstrated high performance in labeling processes, achieving a success rate of 99.2% in labeling parameters and a success rate of 100% in other areas. For nonlabeling parameters, the average labeling time per tube was measured at 8.96 seconds, with a 100% success rate in tube handling and critical stock warnings. Technical issues were promptly resolved, affirming the NESLI robot's effectiveness and reliability in automating the tube-labeling processes. Robotic systems using AI, such as NESLI, have the potential to increase process efficiency and reduce errors in the preanalytical phase of laboratory testing. Integration of such systems into comprehensive information systems is crucial for optimizing phlebotomy services and ensuring timely and accurate diagnostics.