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Clinical Pathology

Genetic analysis reveals Lipoprotein(a) is significantly more atherogenic than LDL on a per-particle basis

20 Mar, 2024 | 19:24h | UTC

Study 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 | UTC

Study 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 | UTC

Study 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:

Imperiale, T. F.et al, & BLUE-C Study Investigators (2024). Next-Generation Multitarget Stool DNA Test for Colorectal Cancer Screening. N Engl J Med, 390(11), 984-993. DOI: 10.1056/NEJMoa2310336.


Study | Uncovering the potential overuse of laboratory tests by combining cost, abnormal result proportion, and physician variation

11 Aug, 2023 | 15:34h | UTC

Data-driven approach to identifying potential laboratory overuse in general internal medicine (GIM) inpatients – BMJ Open Quality

 


Cohort Study | High-sensitivity troponin’s role in assessing MI and CV death risk in stable CAD patients

7 Aug, 2023 | 15:01h | UTC

High-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

High-Sensitivity Cardiac Troponin for Risk Assessment in Chronic CAD – Journal of the American College of Cardiology

 

Commentary on Twitter

 


RCT | Limited antibiotic efficacy in children with sinusitis lacking nasopharyngeal pathogens

27 Jul, 2023 | 13:08h | UTC

Identifying 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

 


New Cochrane handbook for systematic reviews of diagnostic test accuracy

25 Jul, 2023 | 14:02h | UTC

Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy – Cochrane Library

Editorial: Evaluating medical tests: introducing the Cochrane 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 | UTC

Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus – Diabetes Care

Executive 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 | UTC

Effectiveness and Costs of Molecular Screening and Treatment for Bacterial Vaginosis to Prevent Preterm Birth: The AuTop Randomized Clinical Trial – JAMA Pediatrics

See 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 | UTC

Reliability 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 | UTC

Performance 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 | UTC

A Statewide Quality Initiative to Reduce Unnecessary Antibiotic Treatment of Asymptomatic Bacteriuria – JAMA Internal Medicine

Related:

Diagnostic stewardship for urinary tract infection: A snapshot of the expert guidance – Cleveland Clinic Journal of Medicine

Study: Hospital Intervention Resulted in a 45% Reduction in the Urine Cultures Ordered

Optimal Urine Culture Diagnostic Stewardship Practice—Results from an Expert Modified-Delphi Procedure – Clinical Infectious Diseases

USPSTF Recommendation Statement: Screening for Asymptomatic Bacteriuria in Adults

Cohort Study: Antibiotic Treatment of Asymptomatic Bacteriuria in Hospitalized Patients is Common, and May be Associated with Longer Duration of Hospitalization

Inappropriate Management of Asymptomatic Patients With Positive Urine Cultures: A Systematic Review and Meta-analysis – Open Forum Infectious Diseases

IDSA Guideline for the Management of Asymptomatic Bacteriuria

 

Commentary on Twitter

 


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 | UTC

Early-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

Serial serum lipase testing after the initial diagnostic workup for inpatients with acute pancreatitis: What is the evidence? – Cleveland Clinic Journal of Medicine

 


Review | Celiac disease: who should I test, and how?

19 Jun, 2023 | 13:54h | UTC

Celiac 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

Performance of non-invasive tests and histology for the prediction of clinical outcomes in patients with non-alcoholic fatty liver disease: an individual participant data meta-analysis – The Lancet Gastroenterology & Hepatology

 


Review | Candidate biomarkers in psychiatric disorders

15 Jun, 2023 | 14:52h | UTC

Candidate 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

ESAIC focused guideline for the use of cardiac biomarkers in perioperative risk evaluation – European Journal of Anaesthesiology

 


SR | Biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome

1 Jun, 2023 | 12:06h | UTC

Biomarkers for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): a systematic review – BMC Medicine

 


Cluster RCT | Point-of-care CRP testing cuts antibiotic prescriptions in respiratory illnesses in primary care

1 Jun, 2023 | 11:58h | UTC

Implementation of point-of-care testing of C-reactive protein concentrations to improve antibiotic targeting in respiratory illness in Vietnamese primary care: a pragmatic cluster-randomised controlled trial – The Lancet Infectious Diseases

Commentary: 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

NT‐proBNP and All‐Cause and Cardiovascular Mortality in US Adults: A Prospective Cohort Study – Journal of the American Heart Association

 


Guideline | Use of non-invasive biomarkers for diagnosis of colorectal neoplasia

10 May, 2023 | 15:46h | UTC

Joint Asian Pacific Association of Gastroenterology (APAGE)–Asian Pacific Society of Digestive Endoscopy (APSDE) clinical practice guidelines on the use of non-invasive biomarkers for diagnosis of colorectal neoplasia – Gut

 


AACC Guidance document on the clinical use of procalcitonin

8 May, 2023 | 13:12h | UTC

AACC Guidance Document on the Clinical Use of Procalcitonin – The Journal of Applied Laboratory Medicine (free for a limited period)

 

Commentary on Twitter

 


Review | Transforming tuberculosis diagnosis

5 May, 2023 | 15:18h | UTC

Transforming tuberculosis diagnosis – Nature Microbiology (if the link is paywalled, try this one)

 

Commentary on Twitter

 


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