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Multidrug-resistant Gram-negative bacterial infections: Key Updates and Practical Strategies

25 Jan, 2025 | 22:53h | UTC

Introduction: This summary highlights essential points from a recent review in The Lancet addressing multidrug-resistant Gram-negative bacterial (MDR-GNB) infections. It discusses the global epidemiology, diagnostic advances, and therapeutic approaches, aiming to guide clinicians in managing these difficult-to-treat pathogens, which include resistant Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii.

Key Recommendations:

Use Rapid Diagnostics to Guide Therapy
- Employ molecular tests (e.g., multiplex PCR) to detect resistance genes quickly and facilitate targeted treatment.
- Consider phenotypic assays (e.g., CarbaNP, carbapenemase inactivation method) and MALDI-TOF for rapid organism identification and mechanism-specific information.
Optimize Antibiotic Selection Based on Resistance Mechanisms
- AmpC-Producing Enterobacterales (e.g., Enterobacter spp.): Use cefepime if in vitro susceptibility is confirmed.
- ESBL-Producing Enterobacterales: Carbapenems (e.g., meropenem) remain the mainstay for serious infections.
- Carbapenem-Resistant Enterobacterales (CRE): Use novel β-lactam/β-lactamase inhibitor agents (e.g., ceftazidime–avibactam, meropenem–vaborbactam, imipenem–relebactam) based on specific carbapenemase mechanisms. For metallo-β-lactamase producers, consider aztreonam plus ceftazidime–avibactam or future co-formulations (e.g., aztreonam–avibactam).
- DTR-Pseudomonas aeruginosa: Ceftolozane–tazobactam is preferred if active in vitro. Ceftazidime–avibactam or imipenem–relebactam may also be options depending on local susceptibility data.
- Carbapenem-Resistant Acinetobacter baumannii (CRAB): High-dose sulbactam combinations (e.g., sulbactam–durlobactam) were studied in combination with imipenem–cilastatin during trials; further data are needed to clarify optimal clinical use.
Consider Non-Antibiotic Modalities for Refractory Cases
- Investigational therapies—such as bacteriophages and antivirulence agents—are under clinical evaluation.
- Fecal microbiota transplantation has shown variable decolonization efficacy in small studies, and randomized trials have yielded limited or inconclusive results.
Emphasize Antimicrobial Stewardship and Infection Control
- Restrict newer agents to cases where standard treatments have failed or resistance patterns require them.
- Maintain rigorous infection control practices (e.g., contact precautions, hand hygiene, isolation measures) to reduce nosocomial spread of MDR-GNB.
- Observational data suggest shorter antibiotic courses (7–10 days) might be adequate in select cases, but robust clinical trial evidence is still pending.

Conclusion:
By combining rapid diagnostics, judicious use of existing and novel antibiotics, and robust infection prevention measures, clinicians can significantly improve outcomes for patients with MDR-GNB infections. However, access to advanced diagnostics and new therapies remains limited in many regions, and further clinical trials are needed to determine optimal treatment and duration strategies. Early mechanism-focused detection and targeted therapy enhance clinical success, reduce toxicity, and help preserve the efficacy of newly approved agents.

Reference:
Macesic N, Uhlemann A-C, Peleg AY. Multidrug-resistant Gram-negative bacterial infections. The Lancet. 2025;405(10474):257-272. DOI: https://doi.org/10.1016/S0140-6736(24)02081-6

Pseudo-Endocrine Disorders: Clinical Realities and Responsible Management

20 Jan, 2025 | 11:42h | UTC

Introduction:

This summary outlines key points from a review discussing “pseudo-endocrine disorders”—conditions that lack scientific proof but gain popularity through misinformation. The text focuses on recognizing such disorders, understanding their purported mechanisms, and guiding clinicians on how to approach patients who have received these unvalidated diagnoses. The review emphasizes evidence-based evaluation, patient education, and compassionate care.

Key Recommendations:

Recognize the Lack of Scientific Validation: Adrenal fatigue, Wilson’s syndrome, and reverse T3 syndrome lack credible evidence. Testing methods (such as salivary cortisol profiles or axillary temperature measurements) are not scientifically validated.
Avoid Non-Evidence-Based Treatments: Preparations like raw adrenal extracts, high-dose liothyronine, or unverified testosterone treatments may harm patients. Such interventions can induce secondary adrenal insufficiency or suppress endogenous hormone production. Similarly, while not strictly an endocrine issue, the use of Low-Dose Naltrexone (LDN) for autoimmune and other disorders lacks sufficient evidence to support its efficacy and should be approached with caution.
Thorough Diagnostic Evaluation: Use established endocrine tests (e.g., ACTH stimulation tests for adrenal function, morning testosterone levels for hypogonadism). It is paramount to differentiate between pseudo-endocrine disorders and actual endocrine conditions. Rule out genuine disorders—such as true adrenal insufficiency, primary vs. secondary hypogonadism, or autoimmune thyroid disease—before attributing symptoms to a pseudo-condition.
Investigate Confounding Factors: Biotin supplements, opioid use, and other medications can invalidate hormone assays or temporarily suppress hormone levels. Conditions like depression, fibromyalgia, or chronic fatigue may underlie nonspecific symptoms but can be overlooked when pseudo-endocrine labels are hastily applied.
Educate and Empower Patients: Counter internet-driven misinformation by explaining the importance of validated testing and proven treatments. Encourage lifestyle measures (healthy diet, exercise, sufficient sleep) while respecting patients’ concerns and emotional distress.
Promote Public Awareness and Professional Advocacy: Physicians can inform the public through media appearances, local or national medical organizations, and educational campaigns. Reporting harmful or fraudulent practices to medical boards can protect the public and uphold standards of care.

Conclusion: Adopting an evidence-based strategy and a patient-centered approach is vital when confronted with “pseudo-endocrine” diagnoses. Valid laboratory testing, careful clinical evaluation, and thoughtful follow-up can rule out legitimate endocrine disorders or detect root causes such as sleep apnea or depression. Honest communication and empathy foster trust, counter misinformation, and safeguard patients from unnecessary or dangerous interventions. Ultimately, a commitment to evidence-based medicine and patient-centered care is the most effective strategy in addressing the challenges posed by pseudo-endocrine disorders.

Reference: McDermott MT. “Pseudo-endocrine Disorders: Recognition, Management, and Action.” Journal of the Endocrine Society, Volume 9, Issue 1, January 2025, bvae226. https://doi.org/10.1210/jendso/bvae226

RCT: Assessing Procalcitonin-Based Antibiotic Management in Critically Ill Patients With Sepsis

7 Jan, 2025 | 14:00h | UTC

Background: Optimal antibiotic duration for sepsis remains uncertain. Procalcitonin (PCT) and C-reactive protein (CRP) are thought to support shorter courses, but prior research was small-scale or at risk of bias. This multicenter, randomized trial (ADAPT-Sepsis) evaluated whether daily PCT- or CRP-guided protocols could reduce antibiotic use without increasing 28-day all-cause mortality in critically ill adults with suspected sepsis.

Objective: To determine if daily biomarker-guided (PCT or CRP) strategies decrease total antibiotic days among critically ill adults while maintaining acceptable 28-day mortality, compared with standard care.

Methods: From 2018 to 2024 (with enrollment paused March–August 2020 due to COVID-19), 2760 adults (≥18 years) on intravenous antibiotics for suspected sepsis (acute organ dysfunction and presumed infection) and likely to continue antibiotics for at least 72 hours were randomized across 41 UK NHS ICUs within 24 hours of antibiotic initiation. They were assigned in a 1:1:1 ratio to (1) daily PCT-guided advice (n=918), (2) daily CRP-guided advice (n=924), or (3) standard care (n=918). Biomarker results were concealed; clinicians received automated daily prompts recommending continuation or discontinuation. The co-primary outcomes were (1) total antibiotic duration (randomization to day 28) and (2) 28-day all-cause mortality. Secondary measures included antibiotic duration for the initial sepsis episode, 90-day mortality, readmissions, and length of stay.

Results: Among 2760 participants (mean age, 60.2 years; 60.3% men; ~50% with septic shock), over 96% provided 28-day data. Patients in the PCT-guided arm had a statistically significant mean reduction in total antibiotic duration vs standard care (9.8 vs 10.7 days; difference, 0.88 days; 95% CI, 0.19–1.58; p=0.01). The PCT strategy met the prespecified 5.4% noninferiority margin for 28-day mortality (20.9% vs 19.4%; absolute difference, 1.57; 95% CI, –2.18 to 5.32; p=0.02), implying noninferiority but not fully excluding a small risk of excess mortality. CRP-guided protocols did not shorten total antibiotic use (10.6 vs 10.7 days; p=0.79) and were inconclusive for noninferiority regarding mortality (21.1% vs 19.4%; difference, 1.69; 95% CI, –2.07 to 5.45; p=0.03). Notably, 90-day mortality also showed no significant differences. A post-trial commentary (PulmCCM) emphasized that some uncertainty remains with the 5.4% margin and warned that patient-level randomization could subtly discourage earlier antibiotic discontinuation in standard care, which received no explicit “stop” prompts.

Conclusions: In critically ill patients with suspected sepsis, a PCT-guided antibiotic discontinuation protocol shortened overall antibiotic use by nearly one day without exceeding the predefined noninferiority threshold for 28-day mortality. However, the chosen 5.4% margin allows for the possibility of clinically relevant harm. A CRP-guided protocol did not reduce total antibiotic use and showed inconclusive mortality findings.

Implications for Practice: Adopting PCT-based stewardship may modestly decrease antibiotic exposure without a clear short-term mortality penalty, potentially limiting antibiotic resistance. Clinicians should remain vigilant, recognizing the risk tolerance implied by the 5.4% margin. PCT results should complement, not replace, comprehensive clinical judgment.

Study Strengths and Limitations: Strengths include the large sample size, multi-center design, blinded biomarker allocation, and distinct emphasis on both effectiveness and safety outcomes. Limitations include the acceptance of a 5.4% potential excess mortality as the noninferiority threshold, uncertainty about rare but significant harms, and the possibility of bias introduced by patient-level randomization. Generalizability to lower-resource settings may also be limited.

Future Research: Further randomized trials with lower noninferiority margins or cluster-level allocation are needed to better define the safety and efficacy of PCT-guided strategies for reducing antibiotic duration in sepsis. Additional investigations are needed for long-term patient-centered outcomes, cost-effectiveness, and the role of alternative biomarkers or combined strategies in sepsis care.

Reference:

Dark P, Hossain A, McAuley DF, et al. Biomarker-Guided Antibiotic Duration for Hospitalized Patients With Suspected Sepsis: The ADAPT-Sepsis Randomized Clinical Trial. JAMA. 2024; published online December 9. DOI: http://doi.org/10.1001/jama.2024.26458

PulmCCM Commentary: “Is procalcitonin ‘safe’ to guide antibiotic use in patients with sepsis? ADAPT-Sepsis tests the strategy in the U.K., with global ambitions.” Jan 02, 2025. https://www.pulmccm.org/p/is-procalcitonin-safe-to-guide-antibiotic

Innovative Antimicrobial Susceptibility Testing Bypasses Blood Culture, Promising Faster Sepsis Diagnosis – Nature

18 Aug, 2024 | 14:09h | UTC

Study Design and Population: This study introduces a novel ultra-rapid antimicrobial susceptibility testing (AST) method that bypasses the traditional blood culture process, potentially reducing diagnostic time by 40-60 hours. The method was evaluated using a cohort of 190 hospitalized patients in Korea with suspected sepsis, including those with blood cancers.

Main Findings: The new AST method identified bacterial species in all patients with positive blood infections, achieving a 100% match in species identification. For antimicrobial susceptibility, the method demonstrated a 94.9% categorical agreement with conventional AST methods, with a theoretical turnaround time of 13 ± 2.53 hours, significantly faster than current workflows.

Implications for Practice: This method could improve sepsis treatment by providing same-day results, potentially reducing sepsis-related mortality and the use of broad-spectrum antibiotics. However, further validation in a more diverse patient population is necessary to confirm its clinical efficacy and value.

Reference: Kim, T. H., Kang, J., Jang, H., Joo, H., Lee, G. Y., Kim, H., et al. (2024). Blood culture-free ultra-rapid antimicrobial susceptibility testing. Nature, (2024).

Study: Novel Point-of-Care hs-cTnI Test Shows High Diagnostic Accuracy and Predictive Values for Myocardial Infarction – J Am Coll Cardiol

17 Aug, 2024 | 19:00h | UTC

Study Design and Population: This international, multicenter diagnostic study assessed the clinical and analytical performance of the new high-sensitivity cardiac troponin I (hs-cTnI)-SPINCHIP point-of-care (POC) test. The study involved 1,102 adult patients presenting with acute chest discomfort in emergency departments, with myocardial infarction (MI) diagnoses adjudicated by two independent cardiologists.

Main Findings: The hs-cTnI-SPINCHIP test exhibited strong diagnostic accuracy with an area under the receiver-operating characteristic curve of 0.94, similar to established central laboratory assays. The 0/1-hour algorithm of the test identified 51% of patients as low risk for MI with a sensitivity and negative predictive value of 100%, while it confirmed MI in 27% of patients with a specificity of 90.9% and a positive predictive value of 72.9%. Consistency was observed across different sample types.

Implications for Practice: The SPINCHIP hs-cTnI POC test provides a rapid and accurate option for diagnosing MI in emergency settings, aiding quicker decision-making for ruling out or confirming MI.

Reference: Koechlin L. et al. (2024). Clinical and Analytical Performance of a Novel Point-of-Care High-Sensitivity Cardiac Troponin I Assay. JACC, 84(8), 726–740.

New Guidelines Recommend Against Routine Vitamin D Testing and Treatment for Healthy Adults – J Clin Endocrinol Metab

4 Aug, 2024 | 19:19h | UTC

Introduction: The Endocrine Society has developed new clinical practice guidelines focused on the use of vitamin D for the prevention of various diseases. These guidelines were created by a multidisciplinary panel, including experts in adult and pediatric endocrinology, internal medicine, obstetrics and gynecology, nutrition, and epidemiology.

Key Points:

1 – Empiric Vitamin D Supplementation in Children and Adolescents:

– Recommended to prevent nutritional rickets.

– May lower the risk of respiratory tract infections.

– Dosage in trials ranged from 300 to 2000 IU daily, with an average of about 1200 IU per day.

2 – Empiric Vitamin D Supplementation or Testing in Adults Under 75:

– Not recommended for generally healthy adults without specific indications.

3 – Empiric Vitamin D Supplementation in Adults Over 75:

– Suggested due to its potential to lower the risk of mortality.

– Treatment should be empirical, no testing recommended if there are no established indications for testing (e.g., hypocalcemia).

– Recommended daily rather than intermittent high doses. Dosage in clinical trials ranged from 400 to 3333 IU daily equivalent.

4 – Vitamin D Supplementation During Pregnancy:

– Suggested to lower the risk of preeclampsia, intrauterine mortality, preterm birth, small-for-gestational-age birth, and neonatal mortality.

– Empiric supplementation recommended without routine 25(OH)D testing unless there are established indications for testing.

– Dosages in trials ranged from 600 to 5000 IU daily equivalent, with an average of about 2500 IU per day.

5 – Vitamin D and High-Risk Prediabetes:

– Suggested to reduce the progression to diabetes.

– In clinical trials, vitamin D dosages ranged from 842 to 7543 IU daily. The estimated weighted average was approximately 3500 IU per day.

6 – Routine 25(OH)D Testing:

– Not recommended for the general population, including those with obesity or dark complexion.

– No clear evidence defining optimal target levels for disease prevention.

Conclusion: These guidelines emphasize the importance of targeted vitamin D supplementation for specific age groups and conditions, while advising against routine testing for vitamin D levels in the general population. Empiric supplementation is considered beneficial, particularly in children, pregnant women, and older adults, and is feasible, cost-effective, and generally acceptable.

Guideline Reference: Demay, M. B., et al. (2024). Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline. The Journal of Clinical Endocrinology & Metabolism, 109, 1907-1947. Available at: https://doi.org/10.1210/clinem/dgae290

Cohort Study: APOE4 Homozygosity as a Distinct Genetic Form of Alzheimer’s Disease with Early Biomarker Changes – Nat Med

25 May, 2024 | 18:55h | UTC

This 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):

Juan Fortea et al. (2024). APOE4 Homozygosity as a Distinct Genetic Form of Alzheimer’s Disease with Early Biomarker Changes. Nature Medicine. DOI: https://doi.org/10.1038/s41591-024-02931-w

FDA grants approval for Colosense, a noninvasive stool RNA-based test for colorectal cancer screening

11 May, 2024 | 17:48h | UTC

Geneoscopy, 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 | UTC

Study 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):

Ayers, T. et al. (2024). Comparison of Tuberculin Skin Testing and Interferon-γ Release Assays in Predicting Tuberculosis Disease. JAMA Network Open, 7(4), e244769. DOI: https://doi.org/10.1001/jamanetworkopen.2024.4769.

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

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 | 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

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 | 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

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

🔥🔥🔥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