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Frontiers in Cellular and Infection... 2023Oral and/or tongue swabs have demonstrated ability to detect in adults with pulmonary tuberculosis (TB). Swabs provide useful alternative specimens for diagnosis of TB...
INTRODUCTION
Oral and/or tongue swabs have demonstrated ability to detect in adults with pulmonary tuberculosis (TB). Swabs provide useful alternative specimens for diagnosis of TB using molecular assays however, the diagnostic pickup by culture requires further improvement and development. Several studies identified the presence of differentially culturable tubercle bacilli (DCTB) populations in a variety of clinical specimens. These organisms do not grow in routine laboratory media and require growth factors in the form of culture filtrate (CF) from logarithmic phase cultures of H37Rv.
METHODS
Herein, we compared the diagnostic performance of sputum and tongue swabs using Mycobacterial Growth Indicator Tube (MGIT) assays, Auramine smear, GeneXpert and DCTB assays supplemented with or without CF.
RESULTS
From 89 eligible participants, 83 (93%), 66 (74%) and 79 (89%) were sputum positive by MGIT, smear and GeneXpert, respectively. The corresponding tongue swabs displayed a lower sensitivity with 39 (44%), 2 (2.0%) and 18 (20%) participants respectively for the same tests. We aimed to improve the diagnostic yield by utilizing DCTB assays. Sputum samples were associated with a higher positivity rate for CF-augmented DCTB at 82/89 (92%) relative to tongue swabs at 36/89 (40%). Similarly, sputum samples had a higher positivity rate for DCTB populations that were CF-independent at 64/89 (72%) relative to tongue swabs at 26/89 (29%). DCTB positivity increased significantly, relative to MGIT culture, for tongue swabs taken from HIV-positive participants. We next tested whether the use of an alternative smear stain, DMN-Trehalose, would improve diagnostic yield but noted no substantial increase.
DISCUSSION
Collectively, our data show that while tongue swabs yield lower bacterial numbers for diagnostic testing, the use of growth supplementation may improve detection of TB particularly in HIV-positive people but this requires further interrogation in larger studies.
Topics: Adult; Humans; Tuberculosis, Pulmonary; Bacillus; Firmicutes; Mycobacterium tuberculosis; Lacticaseibacillus casei; HIV Infections
PubMed: 37743867
DOI: 10.3389/fcimb.2023.1186191 -
The Lancet. Microbe Apr 2024Accurate diagnosis is pivotal for implementing strategies for surveillance, control, and elimination of schistosomiasis. Despite their low sensitivity in low-endemicity... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Accurate diagnosis is pivotal for implementing strategies for surveillance, control, and elimination of schistosomiasis. Despite their low sensitivity in low-endemicity areas, microscopy-based urine filtration and the Kato-Katz technique are considered as reference diagnostic tests for Schistosoma haematobium and Schistosoma mansoni infections, respectively. We aimed to collate all available evidence on the accuracy of other proposed diagnostic techniques.
METHODS
In this systematic review and meta-analysis, we searched PubMed, Embase, the Cochrane Library, and LILACS for studies published from database inception to Dec 31, 2022, investigating the sensitivity and specificity of diagnostic tests for S haematobium and S mansoni infections against Kato-Katz thick smears or urine microscopy (reference tests) involving adults (aged ≥18 years), school-aged children (aged 7 to 18 years), or preschool-aged children (aged 1 month to 7 years). We extracted raw data on true positives, true negatives, false positives, and false negatives for the diagnostic tests and data on the number of participants, study authors, publication year, journal, study design, participants' age and sex, prevalence of Schistosoma infection, and treatment status. To account for imperfect reference tests, we used a hierarchical Bayesian latent class meta-analysis to model test accuracy.
FINDINGS
Overall, we included 121 studies, assessing 28 different diagnostic techniques. Most studies (103 [85%] of 121) were done in Africa, 14 (12%) in South America, one (1%) in Asia, and one (1%) in an unknown country. Compared with the reference test, Kato-Katz thick smears, circulating cathodic antigen urine cassette assay version 1 (CCA1, 36 test comparisons) had excellent sensitivity (95% [95% credible interval 88-99]) and reasonable specificity (74% [63-83]) for S mansoni. ELISA-based tests had a performance comparable to circulating cathodic antigen, but there were few available test comparisons. For S haematobium, proteinuria (42 test comparisons, sensitivity 73% [62-82]; specificity 94% [89-98]) and haematuria (75 test comparisons, sensitivity 85% [80-90]; specificity 96% [92-99]) reagent strips showed high specificity, with haematuria reagent strips having better sensitivity. Despite limited data, nucleic acid amplification tests (NAATs; eg, PCR or loop-mediated isothermal amplification [LAMP]) showed promising results with sensitivity estimates above 90%. We found an unclear risk of bias of about 70% in the use of the reference or index tests and of 50% in patient selection. All analyses showed substantial heterogeneity (I>80%).
INTERPRETATION
Although NAATs and immunological diagnostics show promise, the limited information available precludes drawing definitive conclusions. Additional research on diagnostic accuracy and cost-effectiveness is needed before the replacement of conventional tests can be considered.
FUNDING
WHO and Luxembourg Institute of Health.
Topics: Child; Child, Preschool; Adult; Animals; Humans; Adolescent; Schistosoma mansoni; Schistosoma haematobium; Hematuria; Reagent Strips; Microscopy; Bayes Theorem; Feces; Antigens, Helminth; Urinalysis; Schistosomiasis haematobia; Diagnostic Tests, Routine
PubMed: 38467130
DOI: 10.1016/S2666-5247(23)00377-4 -
Genes Jul 2023Heterozygous carriers of pathogenic/likely pathogenic variants in autosomal recessive disorders seem to be asymptomatic. However, in recent years, an increasing number... (Review)
Review
Heterozygous carriers of pathogenic/likely pathogenic variants in autosomal recessive disorders seem to be asymptomatic. However, in recent years, an increasing number of case reports have suggested that mild and unspecific symptoms can occur in some heterozygotes, as symptomatic heterozygotes have been identified across different disease types, including neurological, neuromuscular, hematological, and pulmonary diseases. The symptoms are usually milder in heterozygotes than in biallelic variants and occur "later in life". The status of symptomatic heterozygotes as separate entities is often disputed, and alternative diagnoses are considered. Indeed, often only a thin line exists between dual, dominant, and recessive modes of inheritance and symptomatic heterozygosity. Interestingly, recent population studies have found global disease effects in heterozygous carriers of some genetic variants. What makes the few heterozygotes symptomatic, while the majority show no symptoms? The molecular basis of this phenomenon is still unknown. Possible explanations include undiscovered deep-splicing variants, genetic and environmental modifiers, digenic/oligogenic inheritance, skewed methylation patterns, and mutational burden. Symptomatic heterozygotes are rarely reported in the literature, mainly because most did not undergo the complete diagnostic procedure, so alternative diagnoses could not be conclusively excluded. However, despite the increasing accessibility to high-throughput technologies, there still seems to be a small group of patients with mild symptoms and just one variant of autosomes in biallelic diseases. Here, we present some examples, the current state of knowledge, and possible explanations for this phenomenon, and thus argue against the existing dominant/recessive classification.
Topics: Humans; Heterozygote; Inheritance Patterns; Knowledge; Multifactorial Inheritance; Protein Processing, Post-Translational
PubMed: 37628614
DOI: 10.3390/genes14081562 -
Laryngo- Rhino- Otologie May 2024The laryngotracheal junction is an anatomical region with special pathophysiological features. This review presents clinical pictures and malformations that manifest... (Review)
Review
The laryngotracheal junction is an anatomical region with special pathophysiological features. This review presents clinical pictures and malformations that manifest pre-dilectively at this localisation in children and adolescents as well as in adults. The diagnostic procedure is discussed. The possibilities of surgical reconstruction are presented depending on the pathology and age of the patient.
Topics: Humans; Trachea; Larynx; Adolescent; Child; Plastic Surgery Procedures; Adult; Laryngostenosis
PubMed: 38697146
DOI: 10.1055/a-2181-9576 -
International Journal of Cardiology Jun 2024With emerging therapies, early diagnosis of heart failure with preserved ejection fraction (HFpEF) comes to the fore. Whilst the reference standard of exercise-stress... (Review)
Review
Prognostic and diagnostic implications of impaired rest and exercise-stress left atrial compliance in heart failure with preserved ejection fraction: Insights from the HFpEF stress trial.
BACKGROUND
With emerging therapies, early diagnosis of heart failure with preserved ejection fraction (HFpEF) comes to the fore. Whilst the reference standard of exercise-stress right heart catheterisation is well established, the clinical routine struggles between feasibility of exercise-stress and diagnostic accuracy of available tests.
METHODS
The HFpEF Stress Trial (DZHK-17) prospectively enrolled 75 patients with exertional dyspnoea and echocardiographic signs of diastolic dysfunction (E/e' > 8) who underwent simultaneous rest and exercise-stress echocardiography and right heart catheterisation (RHC). HFpEF was defined according to pulmonary capillary wedge pressure (HFpEF: PCWP rest: ≥15 mmHg stress: ≥25 mmHg). Patients were classified as non-cardiac dyspnoea (NCD) in the absence of HFpEF and cardiovascular disease. LA compliance was defined as reservoir strain (Es)/(E/e'). Follow-up was conducted after 4 years to evaluate cardiovascular hospitalisation (CVH).
RESULTS
The final study population included 68 patients (HFpEF n = 34 and NCD n = 34) of which 23 reached the clinical endpoint, 1 patient was lost to follow-up. Patients with HFpEF according to the HFA-PEFF score (≥5 points) had significantly lower LA compliance at rest (p < 0.001) compared to patients with a score ≤ 4. LA compliance at rest outperformed E/e' (AUC 0.78 vs 0.87, p = 0.024) and showed a statistical trend to outperform Es (AUC 0.79 vs 0.87, p = 0.090) for the diagnosis of HFpEF. LA compliance at rest predicted CVH (HR 2.83, 95% CI 1.70-4.74, p < 0.001) irrespective of concomitant atrial fibrillation.
CONCLUSIONS
LA compliance at rest can be obtained from clinical routine imaging and bears strong diagnostic and prognostic accuracy. Addition of LA compliance can improve the role of echocardiography as the primary test and gatekeeper.
Topics: Humans; Heart Failure; Stroke Volume; Prognosis; Noncommunicable Diseases; Heart Atria; Dyspnea; Ventricular Function, Left
PubMed: 38471649
DOI: 10.1016/j.ijcard.2024.131949 -
Health Technology Assessment... Jul 2023Magnetic resonance imaging-based technologies are non-invasive diagnostic tests that can be used to assess non-alcoholic fatty liver disease.
BACKGROUND
Magnetic resonance imaging-based technologies are non-invasive diagnostic tests that can be used to assess non-alcoholic fatty liver disease.
OBJECTIVES
The study objectives were to assess the diagnostic test accuracy, clinical impact and cost-effectiveness of two magnetic resonance imaging-based technologies (LiverMultiScan and magnetic resonance elastography) for patients with non-alcoholic fatty liver disease for whom advanced fibrosis or cirrhosis had not been diagnosed and who had indeterminate results from fibrosis testing, or for whom transient elastography or acoustic radiation force impulse was unsuitable, or who had discordant results from fibrosis testing.
DATA SOURCES
The data sources searched were MEDLINE, MEDLINE Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Database of Controlled Trials, Database of Abstracts of Reviews of Effects and the Health Technology Assessment.
METHODS
A systematic review was conducted using established methods. Diagnostic test accuracy estimates were calculated using bivariate models and a summary receiver operating characteristic curve was calculated using a hierarchical model. A simple decision-tree model was developed to generate cost-effectiveness results.
RESULTS
The diagnostic test accuracy review (13 studies) and the clinical impact review (11 studies) only included one study that provided evidence for patients who had indeterminate or discordant results from fibrosis testing. No studies of patients for whom transient elastography or acoustic radiation force impulse were unsuitable were identified. Depending on fibrosis level, relevant published LiverMultiScan diagnostic test accuracy results ranged from 50% to 88% (sensitivity) and from 42% to 75% (specificity). No magnetic resonance elastography diagnostic test accuracy data were available for the specific population of interest. Results from the clinical impact review suggested that acceptability of LiverMultiScan was generally positive. To explore how the decision to proceed to biopsy is influenced by magnetic resonance imaging-based technologies, the External Assessment Group presented cost-effectiveness analyses for LiverMultiScan plus biopsy versus biopsy only. Base-case incremental cost-effectiveness ratio per quality-adjusted life year gained results for seven of the eight diagnostic test strategies considered showed that LiverMultiScan plus biopsy was dominated by biopsy only; for the remaining strategy (Brunt grade ≥2), the incremental cost-effectiveness ratio per quality-adjusted life year gained was £1,266,511. Results from threshold and scenario analyses demonstrated that External Assessment Group base-case results were robust to plausible variations in the magnitude of key parameters.
LIMITATIONS
Diagnostic test accuracy, clinical impact and cost-effectiveness data for magnetic resonance imaging-based technologies for the population that is the focus of this assessment were limited.
CONCLUSIONS
Magnetic resonance imaging-based technologies may be useful to identify patients who may benefit from additional testing in the form of liver biopsy and those for whom this additional testing may not be necessary. However, there is a paucity of diagnostic test accuracy and clinical impact data for patients who have indeterminate results from fibrosis testing, for whom transient elastography or acoustic radiation force impulse are unsuitable or who had discordant results from fibrosis testing. Given the External Assessment Group cost-effectiveness analyses assumptions, the use of LiverMultiScan and magnetic resonance elastography for assessing non-alcoholic fatty liver disease for patients with inconclusive results from previous fibrosis testing is unlikely to be a cost-effective use of National Health Service resources compared with liver biopsy only.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42021286891.
FUNDING
Funding for this study was provided by the Evidence Synthesis Programme of the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 27, No. 10. See the NIHR Journals Library website for further project information.
Topics: Humans; Cost-Benefit Analysis; Liver Cirrhosis; Magnetic Resonance Imaging; Non-alcoholic Fatty Liver Disease; State Medicine
PubMed: 37839810
DOI: 10.3310/KGJU3398 -
BioMed Research International 2023Schistosomiasis is causing high morbidity and significant mortality in endemic areas. Kato-Katz stool examination and urine filtration techniques are the conventional... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Schistosomiasis is causing high morbidity and significant mortality in endemic areas. Kato-Katz stool examination and urine filtration techniques are the conventional methods for the detection of intestinal and urinary schistosomiasis. The most appropriate diagnostic tools for the detection of schistosomiasis especially in low-prevalence settings should be used. Therefore, this study is aimed at investigating the diagnostic accuracy of and diagnostic tools in sub-Saharan Africa.
METHODS
Electronic databases such as PubMed, PubMed Central/Medline, HINARI, Scopus, EMBASE, Science Direct, Google Scholar, and Cochrane Library were reviewed. The pooled estimates and heterogeneity were determined using Midas in Stata 14.0. The diagnostic accuracy of index tests was compared using the hierarchical summary of the receiver operating characteristic (HSROC) curve in Stata 14.0.
RESULTS
Twenty-four studies consisting of 12,370 individuals were tested to evaluate the accuracy of antigen, antibody, and molecular test methods for the detection of and . The pooled estimate of sensitivity and specificity of CCA was 88% (95% CI: 83-92) and 72 (95% CI: 62-80), respectively, when it is compared with parasitological stool examination for detection. On the other hand, ELISA showed a pooled estimate of sensitivity and specificity of 95% (95% CI: 93-96) and 35% (95% CI: 21-52), respectively, for the examination of using stool examination as a reference test. With regard to , the pooled estimate of sensitivity and specificity of polymerase chain reaction was 97% (95% CI: 78-100) and 94% (95% CI: 74-99), respectively. Moreover, the sensitivity and specificity of urine CCA vary between 41-80% and 55-91%, respectively, compared to urine microscopy.
CONCLUSION
The effort of schistosomiasis elimination requires accurate case identification especially in low-intensity infections. This study showed that CCA had the highest sensitivity and moderate specificity for the diagnosis of . Similarly, the sensitivity of ELISA was excellent, but its specificity was low. The diagnostic accuracy of PCR for the detection of was excellent compared to urine microscopic examination.
Topics: Humans; Animals; Microscopy; Schistosoma mansoni; Urinalysis; Africa South of the Sahara; Diagnostic Tests, Routine
PubMed: 37621699
DOI: 10.1155/2023/3769931 -
PloS One 2023We aimed to perform a meta-analysis to find out whether PCT and MDW could be used as accurate diagnostic markers for sepsis. (Meta-Analysis)
Meta-Analysis
AIM
We aimed to perform a meta-analysis to find out whether PCT and MDW could be used as accurate diagnostic markers for sepsis.
METHODS
We searched PUBMED, WOS, and SCOPUS databases. Inclusion criteria were any observational or clinical trials that compared monocyte Distribution Width [MDW] with Procalcitonin [PCT] as diagnostic markers in a patient with sepsis. Case reports, editorials, conference abstracts, and animal studies were excluded. RevMan software [5.4] was used to perform the meta-analysis.
RESULTS
After the complete screening, 5 observational studies were included in the meta-analysis. The total number of patients included in the meta-analysis in the sepsis group is 565 and 781 in the control group. The pooled analysis between the sepsis group and controls showed a statistically significant association between sepsis and increased levels of MDW and PCT [MD = 3.94, 95% CI = 2.53 to 5.36, p-value < 0.00001] and [MD = 9.29, 95% CI = 0.67 to 17.91, p-value = 0.03] respectively. Moreover, the subgroup analysis showed that the p-value of MDW levels [< 0.00001] is more significant than the p-value of PCT levels = 0.03, the p-value between the two subgroups [< 0.00001]. Additionally, the overall ROC Area for MDW [0.790] > the overall ROC Area for PCT [0.760].
CONCLUSION
Our study revealed a statistically significant association between sepsis and increased MDW and PCT levels compared with controls and the overall ROC Area for MDW is higher than the overall ROC Area for PCT, indicating that the diagnostic accuracy of MDW is higher than PCT.MDW can be used as a diagnostic marker for sepsis patients in the emergency department. More multicenter studies are needed to support our findings.
Topics: Humans; Procalcitonin; Biomarkers; Monocytes; ROC Curve; Sepsis; Diagnostic Tests, Routine
PubMed: 37535683
DOI: 10.1371/journal.pone.0288203 -
Journal of Obstetrics and Gynaecology :... Dec 2024The diagnosis of endometriomas in patients with endometriosis is of primary importance because it influences the management and prognosis of infertility and pain.... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The diagnosis of endometriomas in patients with endometriosis is of primary importance because it influences the management and prognosis of infertility and pain. Imaging techniques are evolving constantly. This study aimed to systematically assess the diagnostic accuracy of transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI) in detecting endometrioma using the surgical visualisation of lesions with or without histopathological confirmation as reference standards in patients of reproductive age with suspected endometriosis.
METHODS
PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature and ClinicalTrials.gov databases were searched from their inception to 12 October 2022, using a manual search for additional articles. Two authors independently performed title, abstract and full-text screening of the identified records, extracted study details and quantitative data and assessed the quality of the studies using the 'Quality Assessment of Diagnostic Accuracy Study 2' tool. Bivariate random-effects models were used to determine the pooled sensitivity and specificity, compare the two imaging modalities and evaluate the sources of heterogeneity.
RESULTS
Sixteen prospective studies (10 assessing TVUS, 4 assessing MRI and 2 assessing both TVUS and MRI) were included, representing 1976 participants. Pooled TVUS and MRI sensitivities for endometrioma were 0.89 (95% confidence interval 'CI', 0.86-0.92) and 0.94 (95% CI, 0.74-0.99), respectively (indirect comparison -value of 0.47). Pooled TVUS and MRI specificities for endometrioma were 0.95 (95% CI, 0.92-0.97) and 0.94 (95% CI, 0.89-0.97), respectively (indirect comparison p-value of 0.51). These studies had a high or unclear risk of bias. A direct comparison (all participants undergoing TVUS and MRI) of the modalities was available in only two studies.
CONCLUSION
TVUS and MRI have high accuracy for diagnosing endometriomas; however, high-quality studies comparing the two modalities are lacking.
Topics: Female; Humans; Endometriosis; Prospective Studies; Ultrasonography; Magnetic Resonance Imaging; Sensitivity and Specificity; Diagnostic Tests, Routine
PubMed: 38348799
DOI: 10.1080/01443615.2024.2311664 -
Epigenetics & Chromatin Sep 2023Blood-based tests have public appeal in screening cancers due to their minimally invasive nature, ability to integrate with other routine blood tests, and high...
BACKGROUND
Blood-based tests have public appeal in screening cancers due to their minimally invasive nature, ability to integrate with other routine blood tests, and high compliance. This study aimed to investigate whether certain epigenetic modulation of peripheral blood mononuclear cells (PBMCs) could be a biomarker of colorectal cancer (CRC).
RESULTS
Western blotting of histones in the PBMCs from 40 colorectal cancer patients and 40 healthy controls was performed to identify the crotonylation sites of proteins. The correlation of crotonylation with tumor staging and diagnostic efficacy were analyzed. Crotonylation of H2BK12 (H2BK12cr) was identified significantly upregulated in the PBMCs of CRC patients compared to healthy controls, and were closely related to distant metastasis (P = 0.0478) and late TNM stage (P = 0.0201). Receiver operator characteristic curve (ROC) analysis demonstrated that the area under curve (AUC) of H2BK12cr was 0.8488, the sensitivity was 70%, and the specificity was 92.5%. The H2BK12cr parameter significantly increased the diagnostic effectiveness of CRC compared with the commercial carcinoembryonic antigen assays.
CONCLUSIONS
The H2BK12cr level in PBMCs of CRC patients has a potential to be a biomarker for distinguishing CRC patients from healthy controls with the advantages of easy operation and high diagnostic efficacy.
Topics: Humans; Histones; Leukocytes, Mononuclear; Biomarkers; Epigenomics; Colorectal Neoplasms
PubMed: 37749610
DOI: 10.1186/s13072-023-00509-3