-
Journal of Clinical Medicine Aug 2023RPL and RIF are challenges in reproductive medicine. The immune system plays a pivotal role in endometrial receptivity, successful implantation, and pregnancy...
BACKGROUND
RPL and RIF are challenges in reproductive medicine. The immune system plays a pivotal role in endometrial receptivity, successful implantation, and pregnancy complications. Immunological changes have been associated with RPL and RIF. Understanding immune dysregulation especially in NK and T cell subtypes may lead to better diagnostic concepts and treatments. From July 2019 to August 2020 patients with RPL and RIF underwent a standardized diagnostic procedure including endometrial biopsies. Immune cell analysis was performed using flow cytometry. Patients were contacted in March 2023 and interviewed concerning their pregnancy outcomes following diagnostics.
RESULTS
Out of 68 patients undergoing endometrial biopsies, 49 patients were finally included. Live birth rates were high with 72% in RPL and 86% in RIF. Immune cell analysis revealed that patients with RPL had more cytotoxic CD56CD16 cells, while RIF patients had more CD56 uNK cells. RPL patients with pregnancy complications showed increased NKT cell percentages.
CONCLUSION
Our findings suggest specific immune changes in RPL and RIF patients, offering potential therapeutic targets. Tailored immunotherapy based on endometrial immunophenotyping might be an option, but further research is needed.
PubMed: 37685653
DOI: 10.3390/jcm12175585 -
Orphanet Journal of Rare Diseases Jul 2023Intellectual disability (ID) has a prevalence of 1-3% and aproximately 30-50% of ID cases have a genetic cause. Development of next-generation sequencing has shown a... (Review)
Review
Intellectual disability (ID) has a prevalence of 1-3% and aproximately 30-50% of ID cases have a genetic cause. Development of next-generation sequencing has shown a high diagnostic potential. The aim of this work was to evaluate the diagnostic yield of clinical exome sequencing in 188 ID patients and the economic impact of its introduction in clinical practice. An analysis of diagnostic yield according to the different clinical variables was performed in order to establish an efficient diagnostic protocol for ID patients. Diagnostic yield of clinical exome sequencing was significant (34%) supporting its utility in diagnosis of ID patients. Wide genetic heterogeneity and predominance of autosomal dominant de novo variants in ID patients were observed. Time to diagnosis was shortened and diagnostic study costs decreased by 62% after implementation of clinical exome sequencing. No association was found between any of the variables analyzed and a higher diagnostic yield; added to the fact that many of the diagnoses weren't clinically detectable, the reduction of time to diagnosis and the economic savings with respect to classical diagnostic studies, strengthen the clinical and economical convenience of early implementation of clinical exome sequencing in the diagnostic workup of ID patients in clinical practice.
Topics: Humans; Intellectual Disability; Exome Sequencing; Exome; High-Throughput Nucleotide Sequencing
PubMed: 37480025
DOI: 10.1186/s13023-023-02809-z -
Academic Radiology Feb 2024This study aimed to evaluate the diagnostic accuracies of ventilation/perfusion-single photon emission computed tomography (V/Q-SPECT) imaging modalities for acute... (Meta-Analysis)
Meta-Analysis Review
RATIONALE AND OBJECTIVES
This study aimed to evaluate the diagnostic accuracies of ventilation/perfusion-single photon emission computed tomography (V/Q-SPECT) imaging modalities for acute pulmonary embolism (PE). These included, in addition to V/Q-SPECT, V/Q-SPECT with low-dose computed tomography (CT; V/Q-SPECT-CT), Q-SPECT with low-dose CT (Q-SPECT-CT), and Q-SPECT.
MATERIALS AND METHODS
PubMed, Embase, CINAHL, and Web of Science databases were searched, and studies included if they studied ≥10 adult participants with acute PE and reported data on the imaging tests' diagnostic performance. Data were meta-analyzed using bivariate random effects regression model.
RESULTS
Data from participants totaling 4146 from 11 V/Q-SPECT studies, 785 from 7 V/Q-SPECT-CT studies, 1196 from 7 Q-SPECT-CT studies, and 728 from five Q-SPECT studies were separately meta-analyzed. The bivariate weighted mean sensitivity and specificity were 0.94 (95% confidence interval [CI]: 0.88-0.97) and 0.95 (95% CI: 0.87-0.98) for V/Q-SPECT, 0.95 (95% CI: 0.88-0.98) and 0.99 (95% CI: 0.92-1.00) for V/Q-SPECT-CT, 0.92 (95% CI: 0.79-0.97) and 0.92 (95% CI: 0.83-0.96) for Q-SPECT-CT, and 0.89 (95% CI: 0.76-0.95) and 0.86 (95% CI: 0.67-0.95) for Q-SPECT studies. The positive and negative likelihood ratios (+LRs and -LRs) were 17.4 (6.9-44.0) and 0.06 (0.03-0.13), 76.7 (11.8-498.0) and 0.06 (0.02-0.13), 11.0 (5.3-22.9) and 0.09 (0.04-0.23), and 6.4 (2.6-15.8) and 0.13 (0.07-0.27) for V/Q-SPECT, V/Q-SPECT-CT, Q-SPECT-CT, and Q-SPECTs, respectively.
CONCLUSION
In the diagnosis of acute PE, this meta-analysis showed that V/Q-SPECT-CT had the highest specificity and +LR. Conversely, Q-SPECT showed the lowest specificity and an unfavorably high -LR.
Topics: Adult; Humans; Tomography, Emission-Computed, Single-Photon; Pulmonary Embolism; Acute Disease; Perfusion; Perfusion Imaging; Diagnostic Tests, Routine
PubMed: 37487880
DOI: 10.1016/j.acra.2023.06.024 -
Journal of Medical Internet Research Jul 2023Deep learning (DL) prediction models hold great promise in the triage of COVID-19. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Deep learning (DL) prediction models hold great promise in the triage of COVID-19.
OBJECTIVE
We aimed to evaluate the diagnostic test accuracy of DL prediction models for assessing and predicting the severity of COVID-19.
METHODS
We searched PubMed, Scopus, LitCovid, Embase, Ovid, and the Cochrane Library for studies published from December 1, 2019, to April 30, 2022. Studies that used DL prediction models to assess or predict COVID-19 severity were included, while those without diagnostic test accuracy analysis or severity dichotomies were excluded. QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2), PROBAST (Prediction Model Risk of Bias Assessment Tool), and funnel plots were used to estimate the bias and applicability.
RESULTS
A total of 12 retrospective studies involving 2006 patients reported the cross-sectionally assessed value of DL on COVID-19 severity. The pooled sensitivity and area under the curve were 0.92 (95% CI 0.89-0.94; I=0.00%) and 0.95 (95% CI 0.92-0.96), respectively. A total of 13 retrospective studies involving 3951 patients reported the longitudinal predictive value of DL for disease severity. The pooled sensitivity and area under the curve were 0.76 (95% CI 0.74-0.79; I=0.00%) and 0.80 (95% CI 0.76-0.83), respectively.
CONCLUSIONS
DL prediction models can help clinicians identify potentially severe cases for early triage. However, high-quality research is lacking.
TRIAL REGISTRATION
PROSPERO CRD42022329252; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD 42022329252.
Topics: Humans; COVID-19; Deep Learning; Retrospective Studies; PubMed; Diagnostic Tests, Routine; COVID-19 Testing
PubMed: 37477951
DOI: 10.2196/46340 -
PloS One 2023Postmenopausal bleeding (PMB) is a common gynecologic condition. Although it can be a sign of uterine cancer, most patients have benign etiology. However, research on...
BACKGROUND
Postmenopausal bleeding (PMB) is a common gynecologic condition. Although it can be a sign of uterine cancer, most patients have benign etiology. However, research on quality of diagnostic evaluation for PMB has been limited to cancer patients. To extend this research, we examined the timeliness of diagnostic evaluation for PMB among patients with benign conditions.
METHODS
Using the 2008-2019 MarketScan Research Databases, we identified 499176 patients (456741 with commercial insurance and 42435 with Medicaid insurance) who presented with PMB but did not have gynecologic cancer. For each patient, we measured the time from their PMB reporting to the date of their first diagnostic procedure. The association between patient characteristics and time to first diagnostic procedure was examined using Cox proportional hazards models (for the overall sample and then stratified by insurance type).
RESULTS
Overall, 54.3% of patients received a diagnostic procedure on the same day when they reported PMB and 86.6% received a diagnostic procedure within 12 months after reporting PMB. These percentages were 39.4% and 77.1%, respectively, for Medicaid patients, compared to 55.7% and 87.4%, respectively, for commercially insured patients (p<0.001 for both). Medicaid patients had an 18% lower rate of receiving a diagnostic procedure at any given time point than commercially insured patients (adjusted hazard ratio = 0.82, 95% CI: 0.81-0.83). Meanwhile, older age and non-gynecologic comorbidities were associated with a lower rate whereas concomitant gynecologic conditions and recent use of preventive care were associated with a higher rate of receiving diagnostic procedures. Analysis stratified by insurance type identified additional risk factors for delayed diagnostic procedures (e.g., non-metropolitan versus metropolitan location for commercially insured patients and Black versus White race for Medicaid patients).
CONCLUSION
A sizable proportion of patients did not receive prompt diagnostic evaluation for PMB. Both clinical and non-clinical factors could affect timeliness of evaluation.
Topics: United States; Female; Humans; Postmenopause; Retrospective Studies; Databases, Factual; Genital Neoplasms, Female; Insurance; Uterine Hemorrhage
PubMed: 37682914
DOI: 10.1371/journal.pone.0289692 -
Pediatric Nephrology (Berlin, Germany) Oct 2023Severity of acute kidney injury (AKI) confers higher odds of mortality. Timely recognition and early initiation of preventive measures may help mitigate the injury... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Severity of acute kidney injury (AKI) confers higher odds of mortality. Timely recognition and early initiation of preventive measures may help mitigate the injury further. Novel biomarkers may aid in the early detection of AKI. The utility of these biomarkers across various clinical settings in children has not been evaluated systematically.
OBJECTIVE
To synthesize the currently available evidence on different novel biomarkers for the early diagnosis of AKI in pediatric patients.
DATA SOURCES
We searched four electronic databases (PubMed, Web of Science, Embase, and Cochrane Library) for studies published between 2004 and May 2022.
STUDY ELIGIBILITY CRITERIA
Cohort and cross-sectional studies evaluating the diagnostic performance of biomarkers in predicting AKI in children were included.
PARTICIPANTS AND INTERVENTIONS
Participants in the study included children (aged less than 18 years) at risk of AKI.
STUDY APPRAISAL AND SYNTHESIS METHODS
We used the QUADAS-2 tool for the quality assessment of the included studies. The area under the receiver operating characteristics (AUROC) was meta-analyzed using the random-effect inverse-variance method. Pooled sensitivity and specificity were generated using the hierarchical summary receiver operating characteristic (HSROC) model.
RESULTS
We included 92 studies evaluating 13,097 participants. Urinary NGAL and serum cystatin C were the two most studied biomarkers, with summary AUROC of 0.82 (0.77-0.86) and 0.80 (0.76-0.85), respectively. Among others, urine TIMP-2*IGFBP7, L-FABP, and IL-18 showed fair to good predicting ability for AKI. We observed good diagnostic performance for predicting severe AKI by urine L-FABP, NGAL, and serum cystatin C.
LIMITATIONS
Limitations were significant heterogeneity and lack of well-defined cutoff value for various biomarkers.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
Urine NGAL, L-FABP, TIMP-2*IGFBP7, and cystatin C showed satisfactory diagnostic accuracy in the early prediction of AKI. To further improve the performance of biomarkers, they need to be integrated with other risk stratification models.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO (CRD42021222698). A higher resolution version of the Graphical abstract is available as "Supplementary information".
Topics: Humans; Child; Lipocalin-2; Tissue Inhibitor of Metalloproteinase-2; Cystatin C; Cross-Sectional Studies; Biomarkers; Acute Kidney Injury; Diagnostic Tests, Routine
PubMed: 36862250
DOI: 10.1007/s00467-023-05891-4 -
Biomedical Reports Sep 2023Gastric cancer (GC) remains a disease with poor prognosis despite increasing availability of more effective targeted treatment. This may be in part due to the difficulty... (Review)
Review
Gastric cancer (GC) remains a disease with poor prognosis despite increasing availability of more effective targeted treatment. This may be in part due to the difficulty in selecting patients for appropriate treatment. Conventional taxonomic classifications of GC are ill-suited to make full use of recent advances in personalised therapy. In the past decade a number of molecular classifications have been proposed to address this; however, to date, there has been little implementation in the diagnostic routine. The lack of harmonisation between these classifications, the complexity and unavailability of some of the tests required plus the demands on time and resources, all contribute to poor uptake in the diagnostic routine. In the present study, these classifications were reviewed and an inclusive working classification that includes their main points, focuses on prognosis and treatment options and can be delivered using four on-slide tests ( hybridization for Epstein-Barr encoding region and immunohistochemistry for mismatch repair, E-cadherin and p53) is proposed. These tests can be performed on paraffin-embedded tissue and could be available in the majority of histopathology laboratories. The proposed classification also includes reflex testing for specific biomarkers relevant to treatment selection.
PubMed: 37614984
DOI: 10.3892/br.2023.1640 -
Clinics in Liver Disease Feb 2024Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive inflammation and fibrosis of the biliary tree leading to biliary... (Review)
Review
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by progressive inflammation and fibrosis of the biliary tree leading to biliary strictures, cholangitis, and cirrhosis. Early in presentation, patients may have normal liver tests, though over time develop a cholestatic pattern of liver injury. Diagnosis is made radiographically with magnetic resonance or endoscopic cholangiography. While several autoantibodies are associated with PSC, none have proven to have adequate diagnostic utility. Liver biopsy is rarely recommended unless to evaluate for small-duct PSC or overlap syndrome. Elastography, in various forms, is an effective, non-invasive modality to evaluate liver fibrosis in PSC.
Topics: Humans; Cholangitis, Sclerosing; Elasticity Imaging Techniques; Cholestasis; Liver Cirrhosis; Diagnostic Tests, Routine
PubMed: 37945157
DOI: 10.1016/j.cld.2023.07.007 -
Genes Mar 2024Neurodevelopmental disorders are a group of complex multifactorial disorders characterized by cognitive impairment, communication deficits, abnormal behaviour, and/or...
Neurodevelopmental disorders are a group of complex multifactorial disorders characterized by cognitive impairment, communication deficits, abnormal behaviour, and/or motor skills resulting from abnormal neural development. Copy number variants (CNVs) are genetic alterations often associated with neurodevelopmental disorders. We evaluated the diagnostic efficacy of the array-comparative genomic hybridization (a-CGH) method and its relevance as a routine diagnostic test in patients with neurodevelopmental disorders for the identification of the molecular alterations underlying or contributing to the clinical manifestations. In the present study, we analysed 1800 subjects with neurodevelopmental disorders using a CGH microarray. We identified 208 (7%) pathogenetic CNVs, 2202 (78%) variants of uncertain significance (VOUS), and 504 (18%) benign CNVs in the 1800 patients analysed. Some alterations contain genes potentially related to neurodevelopmental disorders including , , , , , , , , , , , , , and . The identification of interesting significant genes related to neurological disorders with a-CGH is therefore an essential step in the diagnostic procedure, allowing a better understanding of both the pathophysiology of these disorders and the mechanisms underlying their clinical manifestations.
Topics: Humans; Neurodevelopmental Disorders; DNA Copy Number Variations; Female; Male; Comparative Genomic Hybridization; Italy; Child; Adolescent; Child, Preschool
PubMed: 38674362
DOI: 10.3390/genes15040427 -
European Radiology Oct 2023To perform a systematic review comparing the diagnostic accuracy of MRI vs. CT for assessing pancreatic ductal adenocarcinoma (PDAC) vascular invasion. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To perform a systematic review comparing the diagnostic accuracy of MRI vs. CT for assessing pancreatic ductal adenocarcinoma (PDAC) vascular invasion.
METHODS
MEDLINE, EMBASE, Cochrane Central, and Scopus were searched until December 2021 for diagnostic accuracy studies comparing MRI vs. CT to evaluate vascular invasion of pathologically confirmed PDAC in the same patients. Findings on resection or exploratory laparotomy were the preferred reference standard. Data extraction, risk of bias, and applicability assessment were performed by two authors using the Quality Assessment of Diagnostic Accuracy Studies-Comparative Tool. Bivariate random-effects meta-analysis and meta-regression were performed with 95% confidence intervals (95% CI).
RESULTS
Three studies were included assessing 474 vessels without vascular invasion and 65 with vascular invasion in 107 patients. All patients were imaged using MRI at ≥ 1.5 T and a pancreatic protocol CT. No difference was shown between MRI and CT for diagnosing PDAC vascular invasion: MRI/CT sensitivity (95% CI) were 71% (47-87%)/74% (56-86%), and specificity were 97% (94-99%)/97% (94-98%). Sources of bias included selection bias from only a subset of CT patients undergoing MRI and verification bias from patients with unresectable disease not confirmed on surgery. No patients received neoadjuvant therapy prior to staging.
CONCLUSIONS
Based on limited data, no difference was observed between MRI and pancreatic protocol CT for PDAC vascular invasion assessment. MRI may be an adequate substitute for pancreatic protocol CT in some patients, particularly those who have already had a single-phase CT. Larger and more recent cohort studies at low risk of bias, including patients who have received neoadjuvant therapy, are needed.
CLINICAL RELEVANCE STATEMENT
Abdominal MRI performed similarly to pancreatic protocol CT at assessing pancreatic ductal adenocarcinoma vascular invasion, suggesting local staging is adequate in some patients using MRI. More data are needed using larger, more recent cohorts including patients with neoadjuvant treatment.
KEY POINTS
• Based on limited data, no difference was found between MRI and pancreatic protocol CT sensitivity and specificity for diagnosing PDAC vascular invasion (p = 0.81, 0.73 respectively). • Risk of bias could be reduced in future PDAC MRI vs CT comparative diagnostic test accuracy research by ensuring all enrolled patients undergo both imaging modalities being compared in random order and regardless of the findings on either modality. • More studies are needed that directly compare the diagnostic performance of MRI and CT for PDAC staging after neoadjuvant therapy.
Topics: Humans; Pancreatic Neoplasms; Adenocarcinoma; Tomography, X-Ray Computed; Magnetic Resonance Imaging; Carcinoma, Pancreatic Ductal; Sensitivity and Specificity; Diagnostic Tests, Routine
PubMed: 37083741
DOI: 10.1007/s00330-023-09659-0