Diagnostic Measures Research Articles

Impact of discordance in cardiac troponin T versus I on the performance of triage pathways for myocardial infarction

Abstract Background Biological, analytical, and regulatory differences between high-sensitivity cardiac troponin T (hs-cTnT) and hs-cTnI could lead to an underestimation of the performance of a hs-cTnT-based triage-algorithm if evaluated against a hs-cTnI-based reference standard, and vice versa. Unfortunately, the impact of hs-cTnT/hs-cTnI-discordance on diagnostic performance measures is largely unknown. Methods We quantified the impact of hs-cTnT/hs-cTnI-discordance on the diagnostic performance of the three most widely used and guideline recommended hs-cTnT/I-based triage algorithms for patients presenting with symptoms suggestive of myocardial infarction (MI): the ESC 0/1h-algorithm, the ESC 0/2h-algorithm and the High-STEACS pathway. For the central adjudication of the final diagnosis (reference standard), two independent cardiologists had access to all available clinical information and applied the 4th universal definition of MI, one time with serial hs-cTnT-Elecsys measurements (gold standard T) and a second time with serial hs-cTnI-Architect measurements (gold standard I). The primary diagnostic endpoint for the rule-out of NSTEMI was sensitivity, while for rule-in of NSTEMI specificity. Results Among 7728 eligible patients, the final diagnosis was NSTEMI in 1463 patients (18.9%). Of these, NSTEMI was diagnosed with only one of the two adjudication methods (either gold standard T or I) in 167 (11.4%) patients. When the three hs-cTnT-based early-triage algorithms were evaluated using gold standard T and gold standard I, sensitivity was very high and comparable. In contrast, when the three hs-cTnI-based early-triage algorithms were evaluated using gold standard T and gold standard I, sensitivity was again very high, but consistently lower when using gold standard T as compared to gold standard I. The difference in sensitivity was 1.1% (95%CI, 0.6–1.7) for ESC hs-cTnI-0/1h (Table 1A), 1.0% (95% CI, 0.5—1.6) for ESC hs-cTnI-0/2h (Table 1B), and 2.6% (95%CI, 1.7—3.5) for High-STEACS (Table 2). The differences observed in specificity mirrored those for sensitivity, i.e. always lower specificity when using the other hs-cTnT/I-assay for adjudication. Conclusion The impact of hs-cTnT/hs-cTnI-discordance on the diagnostic performance of hs-cTnT/I-based triage algorithms is modest, but large enough to result in a fallacious underestimation of the rule-out safety when evaluating hs-cTnI-based strategies using a hs-cTnT-based reference standard.

Routine application of cardiac magnetic resonance imaging in patients with suspected myocarditis from immune checkpoint inhibitor therapy

Abstract Background Cardiovascular adverse events including myocarditis associated with immune checkpoint inhibitor (ICI) therapy remain a challenge in clinical practice. Diagnostic assessment of ICI-related myocarditis (ICI-M) is challenging due to a variable phenotype, confounding effects and limited sensitivity of diagnostic tools. Cardiac magnetic resonance imaging (CMR) is used to diagnose non-ICI myocarditis, but evidence on diagnostic sensitivity is low, particularly in patients with a discrete phenotype. Here, we aim to assess the impact of CMR in patients with suspected ICI-related myocarditis and relate to final diagnosis including endomyocardial biopsy findings. Methods All consecutive patients receiving CMR for suspected ICI-M between September 2019 and January 2024 were included and retrospectively analysed. CMR parameters were correlated with clinical, laboratory and echocardiographic parameters and stratified for presence or absence of myocarditis as per final diagnosis. Results A total of 55 patients who received CMR for suspected ICI-related myocarditis were analysed, including 25 patients with confirmed ICI-M as per final diagnosis and 30 patients with cardiotoxicity other than myocarditis or no cardiotoxicity (ICI-O). The mean age (ICI-M versus ICI-O) was 65.7±13.6 versus (vs.) 67.3±9.9 (p=0.61) years, 32.0% vs. 26.7% (p=0.67) were female, and 40.0% vs. 26.7% (p=0.29) had pre-existing coronary heart disease. Cardiac biomarkers and echocardiographic data did not differ between the groups. In CMR analysis, presence of late gadolinium enhancement (LGE) was associated with ICI-M (56.0% vs. 26.7%, p=0.027). Myocardial oedema was generally rare and not associated with ICI-M. Endomyocardial biopsy (EMB) was used in 6 out of 55 patients (10.9%) with suspected ICI-M. In 4 of these 6 patients (66.7%) EMB confirmed ICI-M diagnosis. Of note, only 2/4 patients with EMB-confirmed myocarditis showed abnormal CMR findings. Conclusion The diagnostic assessment of ICI-M is challenged by low sensitivity of common diagnostic measures, often requiring a multimodal approach. Presence of LGE in CMR was associated with ICI-M, but sensitivity and specificity are low. Our data emphasize the high value of EMB in patients with clinically suspected ICI-M despite inconspicuous CMR. Prospective data to improve diagnostic criteria are needed.

Using Bland-Altman plot-based harmonization algorithm to optimize the harmonization for immunoassays.

Harmonization has been recommended by theInternational Organization for Standard (ISO) to achieve equivalent results across invitro diagnostic measurement devices (IVD-MDs). We aim to evaluate the effectiveness of Bland-Altman plot-based harmonization algorithm (BA-BHA) created in this study and compare it with weighted Deming regression-based harmonization algorithm (WD-BHA) proposed in ISO 21151:2020. Eighty patient sera were used as the harmonization reference material (HRM) to develop IVD-MD-specific harmonization algorithms. Another panel of 40 patient sera was used to validate the effectiveness of harmonization algorithms. We compared regression slopes, intercepts, Bland-Altman plot layouts, percent differences, limits of agreement (LoAs), between-method coefficients of variation (CV) before and after harmonization. After harmonization by WD-BHA, acceptable slopes and intercepts between measured values and HRM targets were observed in weighted Deming regression, but not in Passing-Bablok analysis. Mean differences were-5.5 to 5.0 % and differences at specific levels were-33.9 to 23.9 %. LoAs were-64.6 to 74.6 %. Between-method CV was 22.9 % (±12.9 %). However, after harmonization by BA-BHA, both weighted Deming and Passing-Bablok regressions equations presented harmonized results. Mean differences were-0.3 to 0.2 % and differences at specific levels were-1.1 to 1.6 %. LoAs were-23.3 to 23.2 %. Between-method CV was 8.4 % (±4.0 %). The data points were evenly distributed at both sides of the mean in Bland-Altman plots. The inequivalence of test results between different methods can be improved but unacceptable analytical differences at specific levels may be hidden in terms of an acceptable slope and intercept on WD-BHA. The new protocol BA-BHA may be a viable alternative to optimize the harmonization for immunoassays.

Comparing combined testing of cMyBP-C and hs-cTnT with other algorithms for rapid rule-out of acute myocardial infarction in suspected acute coronary syndrome patients

Abstract Background We aimed to compare the diagnostic accuracy of a dual-marker strategy (DMS), incorporating cardiac myosin-binding protein C (cMyBP-C) and high-sensitivity cardiac troponin T (hs-cTnT) testing, against other rapid rule-out algorithms for acute myocardial infarction (AMI). Methods We enrolled 2059 patients presenting to the emergency department with suspected AMI and compared diagnostic measures using the DMS (cMyBP-C <10 ng/L and hs-cTnT≤14 ng/L), serial hs-cTnT sampling (hs-cTnT<14ng/L at different time points within 1-3h), modified European Society of Cardiology (ESC) 0/1h- or 0/3h-protocol (hs-cTnT<5ng/L or <12ng/L & ∆hs-cTnT<3ng/L at 1h or <7ng/L at 3h if hs-cTnT at 1h was not available), as well as the hs-cTnT limit-of-blank (LoB, <3ng/L) and -detection (LoD, <5ng/L) were compared. Negative predictive values (NPV) and sensitivities for AMI rule-out were assessed. Results True-negative rule-out rates using the DMS ranged from 38.1% to 51.6% across all patients, surpassing rates of 6.2%, 17.4%, 45%, and 50.8% achieved by LoB, LoD, serial hs-cTnT sampling, and ESC 0/1h or 0/3h algorithms, respectively. The DMS demonstrated an NPV of 99.7%, similar to serial hs-cTnT sampling and ESC 0/1h or 0/3h algorithms, and 100% for both LoB and LoD. Sensitivities were 98.9%, 98.9%, 100%, and 100%, respectively. Conclusions The DMS - incorporating cMyBP-C and hs-cTnT - effectively rules out AMI, showing non-inferiority to hs-cTnT-only-based rapid rule-out algorithms and offers a promising alternative, potentially enhancing clinical decision-making in emergency settings.

Evaluation of renal functional reserve in patients with preserved renal function and coronary microvascular disease

Abstract Background/introduction Renal Functional Reserve (RFR) stands as a subject of significant scientific discussion,holding promise as a diagnostic tool for early detection of subclinical renal disorders. Literature establishes a link between chronic kidney disease & cardiovascular disease (CVD). Purpose This study aims to assess RFR in patients with coronary microvascular dysfunction (CMD), while maintaining preserved renal function (eGFR≥60ml/min/1.73m2 by CKD-EPI criteria)&proteinuria<400mg/24hr. The investigation seeks to provide insights into the nuanced relationship between renal function&CMD, offering potential early indicators of CVD. Methods This is a single-center, prospective study enrolling patients with CMD. In the absence of significant coronary artery disease, functional coronary circulation assessment was performed. Coronary flow reserve (CFR) & index of microvascular resistance (IMR) were measured invasively with bolus thermodilution technique. In all participants, RFR was estimated by endogenous creatinine clearance after oral protein load (cooked meal, 1.2gr/kg). Normal RFR was defined as≥30 ml/min/1.73m2. Also, patients with CMD were offered 24-hour Ambulatory Blood Pressure Monitoring (ABPM). Results A total of 25 participants have been enrolled so far in study: 11 without CMD - control group [7 female, 64%, mean age: 52.9±8.8 years) & 14 with CMD – CMD group (11 female, 79%, mean age: 53.5±10,3 years). CMD patients were classified into 2 groups, structural & functional endotype (CFR<2.5 & IMR≥25 were considered abnormal). The RFR value for CMD & control group is 7.4±6.3 vs 36.3±5.8 ml/min/1.73m2 respectively (p<0.05). This difference between groups remained statistically significant after controlling for confounding factors. It was found that RFR value for functional & structural CMD endotype was 3.8±2.6 & 9.6±7,2 ml/min/1.73m2 respectively (p=0.06). Furthermore, no statistical significance was found between RFR and IMR, CFR indices. According to data from ABPM, there were no significant differences in ambulatory blood pressure (both systolic and diastolic) between the two endotypes of CMD, as well as no relationship with RFR was observed. However, the proportion of non-dipping BP pattern was significantly higher in functional CMD endotype (p<0.05). It was not found correlation between RFR & non-dipping phenotype. Conclusions Impaired RFR is evident across all individuals experiencing microvascular angina. Furthermore, those with functional CMD exhibit a diminished RFR when compared with their counterparts with structural CMD. RFR does not exhibit a correlation with blood pressure levels or the absence of a nocturnal dipping pattern. In light of the hypothesis asserting that appraising renal functional reserve serves as an early diagnostic measure for subclinical renal disorders, promptly recognizing individuals with distinct phenotypes could facilitate tailoring therapeutic interventions on an individual basis.Functional Coronary AngiogramCMD group baseline characteristics

A IMPORTÂNCIA DOS CUIDADOS ODONTOLÓGICOS EM PACIENTES INTERNADOS EM UNIDADE DE TERAPIA INTENSIVA

Hospitalized patients, specifically in ICUs, are unable to perform daily oral hygiene on their own, and are therefore more susceptible to developing more diseases if their oral cavity is not adequate, which can further aggravate their systemic condition. The objective of the study is to highlight the relevance of dental care in patients hospitalized in ICUs, exploring the main forms of action of the dentist and proposing preventive, diagnostic and therapeutic measures. The methodology was based on a bibliographic review, using articles from the SciELO, PubMed and BVS databases, published between 2014 and 2024. Complete and relevant articles for the topic were considered, while incomplete, duplicated or out-of-time texts were excluded. The reviewed literature highlights the connection between oral health and the prevention of systemic complications, such as heart and lung diseases. This study indicates that the presence of a dentist in multidisciplinary teams in ICUs is essential to prevent oral complications that can worsen the systemic health of patients in addition to prolonging the length of hospital stay.

Anthropometric equation has sufficient diagnostic capacity to identify sarcopenia in women with breast cancer

BackgroundSarcopenia is a common condition in women with breast cancer, however still presents limitations for an effective diagnosis. This study aimed to evaluate the agreement and diagnostic accuracy of an anthropometric equation in diagnosing sarcopenia in women with breast cancer based on different constructs.MethodsCross-sectional study carried out with women with breast cancer aged ≥ 20 years. Sarcopenia was identified according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. Muscle strength was obtained by the handgrip strength test (HGS) and muscle mass (MM) by dual-energy x-ray absorptiometry (DXA) and by the anthropometric predictive equation. For the diagnosis of sarcopenia, eight constructs were proposed based on the MM assessment method (equation or DXA) and different cutoff points. Agreement analyses using Cohen’s Kappa test and diagnostic performance measures were performed. The significance level for all tests was 5%.ResultsA total of 122 women, with a mean age of 55.3 ± 11.4 years, were evaluated. There was a predominance of brown participants (50.8%), insufficiently active (57.4%), with diagnosis time ≤ 3 months (54.1%), and with invasive breast carcinoma (69.7%). The prevalence of sarcopenia ranged from 3.3 to 8.2%, depending on the construct used. The constructs determined from the cutoff points < 16.0 kg/< 7.58 m² and < 23.0 kg/< 7.58 m² were the ones that showed the best ability to detect sarcopenia.ConclusionThe anthropometric equation showed sufficient diagnostic capacity to be used as an alternative in identifying sarcopenia in women with breast cancer.

Evaluation of Measure Dx, a Resource to Accelerate Diagnostic Safety Learning and Improvement.

Several strategies have been developed to detect diagnostic errors for organizational learning and improvement. However, few health care organizations (HCOs) have integrated these strategies into routine operations. To address this gap, the Agency for Healthcare Research and Quality released "Measure Dx: A Resource To Identify, Analyze, and Learn From Diagnostic Safety Events" in 2022. We conducted an evaluation of Measure Dx to measure feasibility of implementation and effects on short-term and intermediate outcomes related to diagnostic safety. Prospective observational study. Teams from 11 HCOs, primarily academic medical centers. Participants were asked to use Measure Dx over approximately 6months and attend monthly virtual learning collaborative sessions to share and discuss approaches to measuring diagnostic safety. Descriptive outcomes were gathered at the HCO level and included uptake of different case-finding strategies and the number of cases reviewed and confirmed to have diagnostic safety improvement opportunities. We collected information on organizational practices related to diagnostic safety at each HCO at baseline and at the conclusion of the project. The 11 HCOs completed all requirements for the evaluation. Each of the four diagnostic safety case finding strategies outlined in Measure Dx were used by at least three HCOs. Across the cohort, participants reviewed 703 cases using a standardized data collection instrument. Of those cases, 224 (31.8%) were identified as diagnostic safety events with improvement opportunities. Unexpectedly, self-ratings on the checklist assessment declined for several organizations. Use of Measure Dx can help accelerate implementation of systematic approaches to diagnostic error measurement and learning across a variety of HCOs, while potentially enabling HCOs to identify opportunities to improve diagnostic safety practices.

Inclusion body myositis: an update.

To review recent advances in our understanding of the epidemiology, pathophysiology, and management of inclusion body myositis (IBM). Recent epidemiologic studies have highlighted the morbidity and mortality associated with IBM, including the impact of dysphagia. Multiomic analyses of IBM tissues have identified new pathogenic pathways and biomarkers for use in clinical trials. New diagnostic criteria and outcome measures have been proposed to improve clinical trial design. Ongoing clinical trials are targeting T cells and autophagy. Improvements in our understanding of IBM pathogenesis are identifying new pathways and biomarkers that need validation in larger cohorts. Exercise remains the primary therapeutic modality available, and new treatment targets are needed.

Concurrent and prospective prediction of community-dwelling adults' psychosocial functioning with the Inventory of Depression and Anxiety Symptoms-II (IDAS-II).

Mood and anxiety disorders involve defining symptoms (e.g., dysphoria, anhedonia) that can impair psychosocial functioning (e.g., self-care, work, social relationships). The present study evaluated the validity of the Inventory of Depression and Anxiety Symptoms-II (IDAS-II; Watson et al., 2012) via convergence with a semistructured interview assessing mood and anxiety disorder symptoms and, moreover, prediction of psychosocial functioning. Community-dwelling adults (N = 601) completed the self-report IDAS-II, a semistructured diagnostic interview, and self-report and interview measures of psychosocial functioning. A retest subsample (ns = 497-501) completed the functioning measures again, on average 8 months later. Supporting our hypotheses, the IDAS-II converged robustly with interview-assessed symptoms and predicted psychosocial functioning significantly, both concurrently and prospectively. Moreover, the IDAS-II predicted functioning significantly better than did the diagnostic interview. These findings support use of the IDAS-II in research and clinical settings to assess mood and anxiety symptoms and their connections to psychosocial impairment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Unraveling Gastric and Small Intestine Gastrointestinal Stromal Tumors: A Review of Our Current Knowledge

Background: Gastrointestinal Stromal Tumors (GISTs) are characterized as round, well–defined mass lesions in the submucosal layer of the gastrointestinal (GI) tract. GISTs often present histological diversity and mutations in c-KIT and PDGFRA genes. Symptoms usually appear as abdominal pain, often accompanied by gastrointestinal bleeding or abdominal mass. The prognosis relies on tumor size, mitotic index, and different mutations, such as KIT mutations. There are a variety of diagnostic measures in the case of GISTs. However, it is important to note that ultrasound is the most common and reliable method for diagnosing gastric GISTs. The treatment methods followed vary from preoperative systemic therapy to surgical interventions. Depending on the type of GIST, professionals decide upon the best treatment plan for the patient. Objective: This review aims to inform the scientific community about the intricacies of gastric and small intestine GISTs to enhance understanding and improve patient management, with a particular focus on the importance of understanding and interpreting the unique microscopic histopathological findings of GISTs.

Prioritising primary care patients with unexpected weight loss for cancer investigation: diagnostic accuracy study (update)

ObjectiveTo quantify the predictive value of unexpected weight loss for cancer according to patient’s age, sex, smoking status, and concurrent clinical features (symptoms, signs, and abnormal blood test results).DesignDiagnostic accuracy...

Capgras Syndrome in Dementia: A Systematic Review of Case Studies.

In an ageing population, dementia has become an imminent healthcare emergency. Capgras syndrome, the most common delusion of misidentification (DMS), is frequently found alongside dementia. Previous research showed that Capgras syndrome has significant negative effects on people living with dementia and their carers due to its complex presentation and impact on their lives. This qualitative systematic review explores the evidence base of the effective management and treatment of Capgras syndrome in dementia. As per our knowledge, this is the first systematic review exploring the symptomatology of Capgras syndrome across different types of dementia. Additionally, it aims to identify the treatments used and their efficacy. Four databases (EMBASE, MEDLINE, PsycINFO, and CINHAL) were screened in March, 2023. Twenty-six studies met the inclusion criteria and were included in the review. Thematic analysis was performed to explore and synthesise the qualitative findings of the studies. Three conceptual themes were identified: diagnostic tools, Capgras syndrome symptomatology, and Capgras syndrome treatment. Results showed that Capgras syndrome in dementia is not diagnosed and treated in a standardised manner. Following the pharmacological intervention, 28% of cases showed resolution of symptoms, and another 28% experienced improvement. However, 7% of cases reported worsening symptoms, and 10.7% experienced no change. While some patients had positive outcomes with specific medications, others either did not respond or experienced a deterioration of their condition. The results highlight that there is no single treatment approach for Capgras syndrome in people living with dementia. This underscores the need for person-centred care, where treatment is tailored to individual needs. The review also reveals a heavy reliance on antipsychotic medications and a noticeable lack of psychosocial interventions. Given the limited benefits and significant risks associated with antipsychotics, future research should prioritise developing and testing psychosocial approaches. Additionally, establishing standardised diagnostic criteria and consistent outcome measures for Capgras syndrome in dementia is crucial for evaluating treatment effectiveness and improving care.

Digitization and subduction of SU(N) gauge theories

The simulation of lattice gauge theories on quantum computers necessitates digitizing gauge fields. One approach involves substituting the continuous gauge group with a discrete subgroup, but the implications of this approximation still need to be clarified. To gain insights, we investigate the subduction of SU(2) and SU(3) to discrete crystal-like subgroups. Using classical lattice calculations, we show that subduction offers valuable information based on subduced direct sums, helping us identify additional terms to incorporate into the lattice action that can mitigate the effects of digitization. Furthermore, we compute the static potentials of all irreducible representations of Σ(360×3) at a fixed lattice spacing. Our results reveal a percent-level agreement with the Casimir scaling of SU(3) for irreducible representations that subduce to a single Σ(360×3) irreducible representation. This provides a diagnostic measure of approximation quality, as some irreducible representations closely match the expected results while others exhibit significant deviations. Published by the American Physical Society 2024

A rare case report of hurthle cell adenoma mimicking malignancy

Thyroid lesions are the most common endocrine diseases, occurring in usually all age groups, though accurate diagnosis still remains a challenge, as due to oncocytic potentials of Thyroid cells leads to like indeterminate or suspicious diagnosis. Long standing benign Thyroid lesion shows atypical presentation suspicious to malignancy. Now a days with the help of WHO classification and available advanced diagnostic measures helping to confirm the diagnosis, avoiding overdiagnosis and wrong treatment. Hence this study review the importance of Histopathological study with coordination with immunohistochemistry (IHC) study, where suspicious thyroid malignant lesion finally diagnosed as benign Hurthle cell/ Oncocytic adenoma in Nodular Goitre.: 72 year old female presented huge neck swelling since one year, was reviewed in our departments of Pathology and ENT. Fine needle aspiration cytology (FNAC) features are suspicious of Malignancy, further Histopathological features were studied with co ordance of IHC study. FNAC features, which were suspicious of Malignancy were further studied with Histopathological and IHC studies diagnosed as Hurthle cell/ Oncocytic adenoma in Nodular Goitre. Histopathology remains the cornerstone for the diagnosis of thyroid oncocytic lesions and also in distinguishing between adenoma and carcinoma.

Development of a transformer-based deep learning algorithm for diabetic peripheral neuropathy classification using corneal confocal microscopy images.

Diabetic peripheral neuropathy (DPN) is common and can go unnoticed until it is firmly developed. This study aims to establish a transformer-based deep learning algorithm (DLA) to classify corneal confocal microscopy (CCM) images, identifying DPN in diabetic patients. Our classification model differs from traditional convolutional neural networks (CNNs) using a Swin transformer network with a hierarchical architecture backbone. Participants included those with (DPN+, n = 57) or without (DPN-, n = 37) DPN as determined by the updated Toronto consensus criteria. The CCM image dataset (consisting of 570 DPN+ and 370 DPN- images, with five images selected from each participant's left and right eyes) was randomly divided into training, validation, and test subsets at a 7:1:2 ratio, considering individual participants. The effectiveness of the algorithm was assessed using diagnostic accuracy measures, such as sensitivity, specificity, and accuracy, in conjunction with Grad-CAM visualization techniques to interpret the model's decisions. In the DPN + group (n = 12), the transformer model successfully predicted all participants, while in the DPN- group (n = 7), one participant was misclassified as DPN+, with an area under the curve (AUC) of 0.9405 (95% CI 0.8166, 1.0000). Among the DPN + images (n = 120), 117 were correctly classified, and among the DPN- images (n = 70), 49 were correctly classified, with an AUC of 0.8996 (95% CI 0.8502, 0.9491). For single-image predictions, the transformer model achieved a superior AUC relative to the ResNet50 model (0.8761, 95% CI 0.8155, 0.9366), the Inception_v3 model (0.8802, 95% CI 0.8231, 0.9374), and the DenseNet121 model (0.8965, 95% CI 0.8438, 0.9491). Transformer-based networks outperform CNN-based networks in rapid binary DPN classification. Transformer-based DLAs have clinical DPN screening potential.

Biological biomarkers in muscle diseases relevant for follow-up and evaluation of treatment.

Muscle diseases cover a diverse group of disorders that in most cases are hereditary. The rarity of the individual muscle diseases provides a challenge for researchers when wanting to establish natural history of the conditions and when trying to develop diagnostic tools, therapies, and outcome measures to evaluate disease progression. With emerging molecular therapies in many genetic muscle diseases, as well as biological therapies for the immune-mediated ones, biological biomarkers play an important role in both drug development and evaluation. In this review, we focus on the role of biological biomarkers in muscle diseases and discuss their utility as surrogate endpoints in therapeutic trials. We categorise these as either 1) disease unspecific markers, 2) markers of specific pathways that may be used for more than one disease or 3) disease-specific markers. We also propose that evaluation of specific therapeutic interventions benefits from biological markers that match the intervention.

Biomarkers suitable for early detection of intrathoracic cancers in primary care: a systematic review.

Intrathoracic cancers, including lung cancer, mesothelioma, and thymoma, present diagnostic challenges in primary care. Biomarkers could resolve some challenges. We synthesized evidence on biomarkers performance for intrathoracic cancer detection in low-prevalence settings. A search in EMBASE and MEDLINE included studies that recruited participants with suspected intrathoracic cancer and reported on at least one diagnostic measure for a validated, non-invasive biomarker. Studies were excluded if participants were recruited based on a pre-established diagnosis. Fifty-two studies were included, reporting on 108 individual biomarkers and panels. CEA, CYFRA 21.1, and VEGF were evaluated for lung cancer and mesothelioma. For lung cancer, CEA and CYFRA 21.1 were most studied, with AUCs of 0.48-0.90 and 0.48-0.83, respectively. Pro-GRP and NSE had the highest NPVs (98.2%, 96.9%), while Early-CDT and MSC panels showed NPVs of 99.3% and 99.0% in smokers. For mesothelioma, Fibrillin-3 and mesothelin plus osteopontin had AUCs of 0.93 and 0.91, respectively. Thymoma panels (Binding AcHR + StrAb) and (Binding AcHR + Modulating AcHR + StrAb) had 100% NPVs in myasthenia gravis patients. The review highlights the performance of some biomarkers. However, few were evaluated in low-prevalence settings. Further evaluation is necessary before implementing these biomarkers for intrathoracic cancers in primary care.

Investigating the Association between Catechol-O-Methyltransferase Gene Activity and Pain Perception in South African Patients with Different Temporomandibular Disorders Diagnoses.

Background: Temporomandibular disorders (TMD) affect a significant portion of the population, with profound psychological, behavioral, and social repercussions. Recent investigations have explored the genetic basis underlying pain perception in individuals with TMD, aiming to elucidate the role of specific genetic factors in modulating the condition. Notably, genetic variations have been implicated in the pathogenesis of TMD, particularly genes involved in pain perception pathways. One of the primary candidates is the Catechol-O-Methyltransferase (COMT) gene, which plays a crucial role in the catecholaminergic system and has been associated with the regulation of nociceptive processes. This study seeks to investigate the correlation between COMT gene activity and pain perception among South African patients diagnosed with varying forms of TMD. Methodology: In this study, a total of 196 participants were enrolled, comprising 97 patients diagnosed with TMD and 99 control participants. The control group was meticulously matched with the TMD group for age, gender, and ethnicity. Data collection involved clinical and radiological investigations, and saliva sampling. The English version of the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) Axis I was utilized to evaluate all TMD participants, focusing on standard diagnostic measures based on clinical signs and symptoms of TMD, which primarily describe common physical manifestations of the disorder. Genomic DNA was extracted from saliva samples, enabling the analysis of single-nucleotide polymorphisms (SNPs) in the COMT gene, specifically targeting polymorphisms rs165774, rs9332377, rs6269, rs4646310, rs165656, and rs4680. Results: The current study demonstrated a pronounced gender disparity, with 80.41% of the participants being female and 19.59% male, suggesting that women in South Africa either exhibit a higher susceptibility to TMD or are more likely to seek treatment for the condition compared to men. The highest prevalence of TMD was observed in the white population (58.76%). Additionally, over 65% of TMD patients were diagnosed with at least two Axis I diagnoses, a figure that increased to 89% for those diagnosed with three Axis I diagnoses. The findings further indicated significant associations between several single-nucleotide polymorphisms (SNPs) in the Catechol-O-Methyltransferase (COMT) gene-specifically rs165656, rs9332377, rs4646310, rs6269, and rs165774-and both TMD and TMD-related pain. Myofascial pain with referral and myalgia showed a strong association with the COMT SNPs rs9332377 and rs4646310. Furthermore, COMT SNP rs4646310 was also associated with disability related to TMD. Conclusions: This study substantiates the hypothesis that pain is prevalent in a considerable proportion of patients affected by TMD. Furthermore, the findings reveal a significant association between COMT gene activity and pain perception in South African patients diagnosed with TMD.

Diagnosis of schizophrenia by integrated saccade scores and associations with psychiatric symptoms, and functioning.

Eye movement as a neurobiological biomarker of schizophrenia. We aim to estimate diagnostic accuracy of integrated pro/antisaccade eye movement measurements to discriminate between healthy individuals and schizophrenic patients. We compared the eye movement performance of 85 healthy individuals and 116 schizophrenia-stable patients during prosaccade and antisaccade tasks. The difference eye movement measurements were accumulated by stepwise discriminant analysis to produce an integrated score. Finally, the diagnostic value of the integrated score was calculated by the receiver operating characteristic (ROC) area under the curve (AUC), and the best sensitivity and specificity were calculated based on the given cutoff values. Using discriminant analysis, an integrated score included the residual gain and latency (step) during the prosaccade test, the error rate, and the corrected error rate during the antisaccade test. We found that the integrated score could well classify schizophrenia patients and healthy individuals with an accuracy of 80.6%. In the ROC, Youden's index was 0.634 (sensitivity = 81.0%, specificity = 82.4%) and AUC was 0.871. There were significant difference patterns of correlation between the severity of psychiatric symptoms and daily functioning and diagnostic eye movement measurements. Using only 2 saccade tasks to discriminate well between schizophrenia patients and healthy controls, suggesting that abnormalities in saccade behavior is a potential biomarker and efficient diagnostic tool for identifying schizophrenia. The underlying neuropathologic mechanisms associated with abnormal saccades may provide insights into the intervention and diagnosis of schizophrenia.