Clinical Pathology
Cohort Study: APOE4 Homozygosity as a Distinct Genetic Form of Alzheimer’s Disease with Early Biomarker Changes – Nat Med
25 May, 2024 | 18:55h | UTCThis cohort study investigated the impact of APOE4 homozygosity on Alzheimer’s disease (AD) by analyzing clinical, pathological, and biomarker data. The study utilized data from the National Alzheimer’s Coordinating Center and five additional large cohorts, comprising a total of 3,297 individuals for the pathological study and 10,039 for the clinical study. Results demonstrated that APOE4 homozygotes exhibited almost universal AD pathology and had significantly higher levels of AD biomarkers from age 55, compared to APOE3 homozygotes. By age 65, nearly all APOE4 homozygotes showed abnormal amyloid levels in cerebrospinal fluid, and 75% had positive amyloid scans, indicating a high biological penetrance of AD. These individuals also exhibited an earlier onset of symptoms, around age 65.1, and the progression and predictability of biomarker changes paralleled those observed in autosomal dominant AD and Down syndrome. However, in the dementia stage, amyloid and tau positron emission tomography scans showed no differences across haplotypes. The study concludes that APOE4 homozygosity represents a genetically distinct form of AD, underscoring the importance of tailored prevention strategies and treatments.
Reference (link to abstract – $ for full-text):
FDA grants approval for Colosense, a noninvasive stool RNA-based test for colorectal cancer screening
11 May, 2024 | 17:48h | UTCGeneoscopy, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved ColoSense™, a noninvasive stool RNA-based test for colorectal cancer (CRC) screening in adults aged 45 and older who are at average risk for CRC.
Test Performance and Specifications:
– Sensitivity and Specificity: In the CRC-PREVENT trial, ColoSense demonstrated a sensitivity of 93% for detecting colorectal cancer and 45% sensitivity for detecting advanced adenomas (AA).
– Technology: ColoSense employs a multi-target stool RNA (mt-sRNA) approach, detecting colorectal neoplasia-associated RNA markers and occult hemoglobin. This method is designed to overcome variability in test performance that can occur with age-related changes in other biomarkers.
– Breakthrough Device Designation: The test has been designated as a Breakthrough Device by the FDA, acknowledging its potential to offer more effective diagnosis compared to existing methods.
– Accessibility: ColoSense is intended to facilitate increased screening uptake by providing a noninvasive alternative to traditional colonoscopy, particularly among populations reticent about invasive procedures.
Clinical Application:
– Screening Recommendations: Approved for individuals at typical average risk for CRC, ColoSense aligns with updated screening guidelines that recommend starting CRC screening at age 45.
– Role in Screening Strategy: ColoSense is indicated for use as a screening tool but is not intended to replace diagnostic or surveillance colonoscopy in individuals at high risk for CRC.
Geneoscopy is working towards a commercial launch of ColoSense in collaboration with Labcorp (NYSE: LH), aiming to make the test available by late 2024 or early 2025. (link to news release)
Diagnostic Study: Enhanced prediction of TB progression with IGRAs compared to tuberculin skin test
27 Apr, 2024 | 18:53h | UTCStudy Design and Population:
This prospective diagnostic study analyzed the predictive accuracy of tuberculosis (TB) tests among 22,020 high-risk participants across 10 US sites from 2012 to 2020. Participants included individuals with close contacts to infectious TB cases, those born in or travelers to high-incidence countries, individuals living with HIV, or belonging to locally prevalent high-risk groups. Testing included two interferon-γ release assays (IGRAs), QuantiFERON-TB Gold In-Tube (QFT-GIT) and SPOT.TB (TSPOT), alongside the traditional tuberculin skin test (TST).
Main Findings:
The study found that both IGRAs, TSPOT and QFT-GIT, showed significantly superior positive predictive value (PPV) for predicting TB disease progression compared to the TST, with PPV ratios of 1.65 (95% CI, 1.35-2.02) and 1.47 (95% CI, 1.22-1.77) respectively. Additionally, when considering a positive TST result, further positive results from either IGRA significantly increased the PPV, emphasizing the enhanced predictive capability of IGRAs over TST alone.
Implications for Practice:
The superior predictive performance of Interferon-γ Release Assays (IGRAs) suggests they should be considered in clinical settings for high-risk populations, if available and feasible, to better identify individuals at increased risk of progressing to active tuberculosis (TB). This enhanced detection capability could guide more targeted preventive treatments, ultimately supporting global efforts toward TB elimination. Clinicians should assess the accessibility and cost-effectiveness of IGRAs to refine decision-making processes in TB prevention strategies, ensuring that the benefits of these advanced diagnostics are balanced against their costs.
Reference (free full-text):
Genetic analysis reveals Lipoprotein(a) is significantly more atherogenic than LDL on a per-particle basis
20 Mar, 2024 | 19:24h | UTCStudy Design and Population: This study utilized genome-wide association studies (GWAS) within the UK Biobank population to examine the atherogenicity of lipoprotein(a) (Lp(a)) compared to low-density lipoprotein (LDL), focusing on their apolipoprotein B (apoB) content. The researchers identified two clusters of single nucleotide polymorphisms (SNPs) associated with mass concentrations of Lp(a) and LDL, comprising 107 and 143 variants, respectively. The sample included subjects from the UK Biobank, allowing for a broad and genetically diverse analysis.
Main Findings: The study’s Mendelian randomization approach found that a 50 nmol/L increase in Lp(a)-apoB was associated with a 1.28 times higher odds ratio (OR) for coronary heart disease (CHD) compared to a 1.04 times increase for the same increment in LDL-apoB. Furthermore, a comparison using polygenic scores demonstrated that the hazard ratio (HR) for CHD per 50 nmol/L increase in apoB was significantly higher for the Lp(a) cluster (1.47) than for the LDL cluster (1.04), suggesting that Lp(a) is approximately 6.6 times more atherogenic than LDL on a per-particle basis.
Implications for Practice: These findings highlight the substantial atherogenic potential of Lp(a) compared to LDL, indicating that Lp(a) should be a key focus for drug intervention strategies in populations at risk for CHD. The marked difference in atherogenicity underscores the importance of targeted treatments and monitoring for individuals with elevated Lp(a) levels.
Reference: Björnson, E., Adiels, M., Taskinen, M.-R., Burgess, S., Chapman, M. J., Packard, C. J., & Borén, J. (2024). Lipoprotein(a) Is Markedly More Atherogenic Than LDL: An Apolipoprotein B-Based Genetic Analysis. Journal of the American College of Cardiology, 83(3), 385-395. DOI: https://doi.org/10.1016/j.jacc.2023.10.039. Access the study here: Link
Clinical validation of a cell-free DNA test for colorectal cancer screening: sensitivity and specificity analysis
20 Mar, 2024 | 19:16h | UTCStudy Design and Population: This study conducted a clinical validation of a cell-free DNA (cfDNA) blood-based test to screen for colorectal cancer in a cohort of 10,258 individuals, 7,861 of whom met the eligibility criteria and were evaluable. The research aimed to assess the test’s performance by comparing its sensitivity for detecting colorectal cancer and its specificity for identifying advanced neoplasia (including colorectal cancer or advanced precancerous lesions) against the outcomes of screening colonoscopy, a standard procedure.
Main Findings: The cfDNA test demonstrated a sensitivity of 83.1% for detecting colorectal cancer, with stage-specific sensitivities of 87.5% for stages I-III cancers. However, its sensitivity for identifying advanced precancerous lesions was notably lower at 13.2%. On the specificity front, the test showed an 89.6% ability to correctly identify individuals without any advanced colorectal neoplasia and had an overall specificity of 89.9% for those with a negative colonoscopy result, indicating no presence of colorectal cancer, advanced precancerous lesions, or non-advanced precancerous lesions.
Implications for Practice: The cfDNA blood-based test presents a promising tool for colorectal cancer screening, boasting substantial sensitivity for colorectal cancer detection and high specificity for advanced neoplasia. Its non-invasive nature could potentially enhance screening adherence, facilitating earlier cancer detection and possibly reducing colorectal cancer-related mortality. However, the test’s low sensitivity for advanced precancerous lesions suggests a need for further research and development to improve early detection capabilities.
Reference: Chung, D.C. et al. A Cell-free DNA Blood-Based Test for Colorectal Cancer Screening. Journal Name, Volume(Issue), Pages. Access the study here: [Link]
Prospective Study: Enhanced detection of colorectal cancer and precancerous lesions with next-generation stool DNA testing
20 Mar, 2024 | 17:41h | UTCStudy Design and Population:
This prospective study evaluated the efficacy of a next-generation multitarget stool DNA test for colorectal cancer screening in asymptomatic adults aged 40 and older. The study encompassed 20,176 participants undergoing screening colonoscopy to determine the test’s sensitivity and specificity in detecting colorectal cancer and advanced neoplasia, including advanced precancerous lesions.
Main Findings:
The next-generation stool DNA test demonstrated a sensitivity of 93.9% for detecting colorectal cancer and a specificity of 90.6% for advanced neoplasia, significantly outperforming the fecal immunochemical test (FIT) in sensitivity for both colorectal cancer and advanced precancerous lesions. However, the test showed slightly lower specificity for advanced neoplasia compared to FIT. No adverse events were reported, indicating the test’s safety for screening purposes.
Implications for Practice:
The findings suggest that the next-generation multitarget stool DNA test offers a superior option for colorectal cancer screening, with significantly higher sensitivity for detecting cancer and advanced precancerous lesions than the currently available FIT. This advance in non-invasive screening technology could lead to earlier detection and treatment of colorectal cancer, potentially improving patient outcomes. Further research may focus on optimizing the balance between sensitivity and specificity to enhance the clinical utility of stool DNA testing.
Reference:
Study | Uncovering the potential overuse of laboratory tests by combining cost, abnormal result proportion, and physician variation
11 Aug, 2023 | 15:34h | UTC
Cohort Study | High-sensitivity troponin’s role in assessing MI and CV death risk in stable CAD patients
7 Aug, 2023 | 15:01h | UTCHigh-Sensitivity Cardiac Troponin for Risk Assessment in Patients With Chronic Coronary Artery Disease – Journal of the American College of Cardiology (link to abstract – $ for full-text)
Commentaries:
High-Sensitivity Troponin Assays May Stratify Risk in Chronic CAD – TCTMD
Commentary on Twitter
In patients with chronic CAD, an elevated #troponin identifies those more likely to have MI or CV death. Routine troponin testing in this setting could inform patient selection for additional treatment. https://t.co/T4HfidPwOA#JACC #cvCAD #CardioTwitter #cvPrev #cvMI pic.twitter.com/2IOU8jsFPj
— JACC Journals (@JACCJournals) August 1, 2023
RCT | Limited antibiotic efficacy in children with sinusitis lacking nasopharyngeal pathogens
27 Jul, 2023 | 13:08h | UTCIdentifying Children Likely to Benefit From Antibiotics for Acute Sinusitis: A Randomized Clinical Trial – JAMA (free for a limited period)
Editorial: Acute Bacterial Sinusitis: Limitations of Test-Based Treatment – JAMA (free for a limited period)
News Release: Bacterial testing in kids with sinusitis could slash antibiotic use – University of Pittsburgh
Commentary: Trial suggests bacterial test could reduce antibiotics in kids with sinusitis – CIDRAP
Commentary on Twitter
In children with acute sinusitis, antibiotic treatment had minimal benefit for those without nasopharyngeal bacterial pathogens. The antibiotic effect did not depend on the color of nasal discharge. https://t.co/hgRx1Qou53 pic.twitter.com/zYs8Mfbjjp
— JAMA (@JAMA_current) July 26, 2023
New Cochrane handbook for systematic reviews of diagnostic test accuracy
25 Jul, 2023 | 14:02h | UTCCochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy – Cochrane Library
News Release: Introducing the new Cochrane Handbook for Diagnostic Test Accuracy – Cochrane Library
Guideline | Laboratory analysis in the diagnosis and management of diabetes mellitus
21 Jul, 2023 | 13:50h | UTCExecutive Summary: Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus – Diabetes Care
RCT | Molecular screening for bacterial vaginosis does not significantly reduce preterm birth rates
21 Jul, 2023 | 13:31h | UTCSee also: Visual Abstract
Cohort study | Poor sensitivity of procalcitonin-on-admission for ruling out bloodstream infections in patients with suspected sepsis
18 Jul, 2023 | 13:39h | UTCReliability of Admission Procalcitonin Testing for Capturing Bacteremia Across the Sepsis Spectrum: Real-World Utilization and Performance Characteristics, 65 U.S. Hospitals, 2008–2017 – Critical Care Medicine (link to abstract – $ for full-text)
TTMV-HPV DNA testing | Promising diagnostic and surveillance tool for HPV-linked oropharyngeal cancer
17 Jul, 2023 | 13:25h | UTCPerformance of Liquid Biopsy for Diagnosis and Surveillance of Human Papillomavirus–Associated Oropharyngeal Cancer – JAMA Otolaryngology–Head & Neck Surgery (free for a limited period)
Invited Commentary: Circulating Human Papillomavirus Tumor DNA—Ready for Prime Time? – – JAMA Otolaryngology–Head & Neck Surgery (free for a limited period)
Quality Improvement Study | Improved asymptomatic bacteriuria management by reduction of unnecessary urine culture requests
14 Jul, 2023 | 12:54h | UTCRelated:
Study: Hospital Intervention Resulted in a 45% Reduction in the Urine Cultures Ordered
USPSTF Recommendation Statement: Screening for Asymptomatic Bacteriuria in Adults
IDSA Guideline for the Management of Asymptomatic Bacteriuria
Commentary on Twitter
???Powerful message from our new study in @JAMAInternalMed: diagnostic stewardship (better use of diagnostic tests) was responsible for ALL the⬇️in unnecessary antibiotic use for ASB. ➕results??nudge to action. Time to??upstream to improve care! https://t.co/yO4UpA6ZKK pic.twitter.com/hXZGvNmVJP
— Valerie Vaughn (@ValerieVaughnMD) July 11, 2023
Podcast | Wisely ordering autoantibodies
28 Jun, 2023 | 13:09h | UTC#399 Wisely Ordering Autoantibodies – ACP IM2023 – The Curbsiders
Perspective | Early-stage lung cancer: using circulating tumor DNA to get personal
26 Jun, 2023 | 00:38h | UTCEarly-Stage Lung Cancer: Using Circulating Tumor DNA to Get Personal – Journal of Clinical Oncology
Review | Serial serum lipase testing after the initial diagnostic workup for inpatients with acute pancreatitis: what is the evidence?
21 Jun, 2023 | 13:27h | UTC
Review | Celiac disease: who should I test, and how?
19 Jun, 2023 | 13:54h | UTCCeliac disease: Who should I test, and how? – Cleveland Clinic Journal of Medicine
M-A | Comparing non-invasive tests, histology for predicting non-alcoholic fatty liver outcomes
15 Jun, 2023 | 14:50h | UTC
Review | Candidate biomarkers in psychiatric disorders
15 Jun, 2023 | 14:52h | UTCCandidate biomarkers in psychiatric disorders: state of the field – World Psychiatry
ESAIC focused guideline for the use of cardiac biomarkers in perioperative risk evaluation
5 Jun, 2023 | 13:37h | UTC
SR | Biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome
1 Jun, 2023 | 12:06h | UTC
Cluster RCT | Point-of-care CRP testing cuts antibiotic prescriptions in respiratory illnesses in primary care
1 Jun, 2023 | 11:58h | UTCCommentary: Use of CRP testing reduced antibiotics for respiratory infections, trial finds – CIDRAP
Cohort Study | NT‐proBNP and all-cause and cardiovascular mortality
31 May, 2023 | 13:59h | UTC