Recent research has found significant associations between albuminuria—but not estimated glomerular filtration (eGFR)—and the lipid composition of HDL in chronic kidney disease (CKD) patients (Clin Chem 2023; doi: doi.org/10.1093/clinchem/hvac216).
CKD patients’ HDL particles are more dysfunctional than those of the general population, so understanding HDL’s liquid composition would provide helpful insight, the researchers hypothesized. To that end, they tested associations of eGFR and albuminuria with relative HDL abundance of ceramides, sphingomyelins, and phosphatidylcholines in 490 participants with CKD.
The researchers isolated HDL from plasma and used targeted lipidomics to quantify the relative abundance of ceramides, sphingomyelins, and phosphatidylcholines per 10 μg of total HDL protein. The researchers evaluated the associations of eGFR and albuminuria with levels of individual lipids and lipid classes including 7 ceramides, 6 sphingomyelins, and 24 phosphatidylcholines via multivariable linear regression, controlling for multiple comparisons via the false discovery rate.
The mean eGFR was 45 mL/ min/1.73 m2. The median albuminuria concentration was 108 mg/g urine creatinine. After adjusting for demographics, past medical history, laboratory values, and medication use, eGFR was not associated with higher relative abundance of any class of lipids or individual lipids.
Greater albuminuria, however, was significantly associated with a higher relative abundance of total ceramides and moderate-long R-chain sphingomyelins, ceramides 22:0 and 24:1, hexosylceramide 16:0, sphingomyelin 16:0, and phosphatidylcholines 29:0, 30:1, and 38:2. The strongest association was for hexosylceramide 16:0 (95% CI, 0.012– 0.032).
The researchers called for further study about mechanisms underlying these relationships.
LIQUID BIOPSY FOR COLON CANCER MAY GUIDE TREATMENT
A liquid biopsy test may identify patients with stage 2 to 4 colorectal cancer (CRC) who are at an increased risk of recurrence and likely to benefit from adjuvant chemotherapy.
Despite standard-of-care treatment, more than 30% of patients with resectable CRC relapse. Japanese researchers aimed to prospectively to validate and build upon previous evidence that ctDNA positivity predicts disease recurrence in early-stage colorectal cancer and to show that ctDNA may enable postsurgical risk stratification and adjuvant chemotherapy (ACT) treatment decision-making (Nat Med 2023; doi: 10.1038/s41591-022-02115-4).
The researchers reported on the GALAXY trial, part of the ongoing CIRCULATE-Japan project. CIRCULATE is collection of trials intended to refine precision medicine for patients with CRC by improving adjuvant therapy choice through ctDNA technology. GALAXY is a prospective, large-scale, observational registry trial that monitors ctDNA in CRC patients at clinical stage 2 to 4 or recurrent CRC following surgery.
The researchers monitored 1,039 people using the Signatera MRD test, which detects circulating tumor DNA (ctDNA) for molecular residual disease (MRD) assessment, treatment response monitoring, and early recurrence monitoring. The median follow-up period was 16.74 months.
They found that patients with ctDNA positivity 4 weeks after surgery had a significantly higher risk of recurrence than those with ctDNA negativity 4 weeks after surgery (hazard ratio (HR) 10.0, P<0.0001). ctDNA positivity at 4 weeks was the most significant prognostic factor associated with recurrence risk in patients with stage 2 or 3 CRC (HR 10.82, P<0.001).
Postsurgical ctDNA positivity also identified patients with stage 2 or 3 CRC who derived benefit from ACT (HR 6.59, P<0.0001). Notably, 4,664 out of 8,374, or 55.7%, of genes selected for the tumor-informed ctDNA assay were found to be unique to each patient, showing the importance of personalized ctDNA analysis based on patient-specific somatic tumor mutations.
The researchers believe that their results can help refine staging criteria in the future by incorporating postsurgical ctDNA status into traditional staging criteria based on tumor size, spread to lymph nodes, and metastasis.
PARAMEDIC-ADMINISTERED TROPONIN TESTING SAVES MONEY
Point-of-care (POC) troponin tests administered by paramedics who conduct risk stratification for patients with acute chest pain could result in substantial cost savings for hospitals, according to new research (JAMA Intern Med; doi: 10.1001/jamainternmed.2022.6409).
POC, high-sensitivity troponin (hsTn) assays may soon be widely available. To analyze whether prehospital point-of-care troponin testing and paramedic risk stratification could result in cost savings compared with existing chest pain care pathways, researchers conducted an economic evaluation of its use in adults with acute chest pain without ST-segment elevation. The researchers used cost-minimization analysis to assess linked ambulance, emergency, and hospital attendance in Australia.
This economic evaluation and data linkage study involved models tested on 188,551 patients. Patients median age was 61.9. The researchers developed and evaluated decision tree models to estimate costs under 3 pathways: usual care, paramedic risk stratification, and POC troponin testing without prehospital discharge, and prehospital discharge and referral to a virtual emergency department (ED) for low-risk patients. The outcome was estimated mean annualized statewide costs for acute chest pain.
Estimated annualized infrastructure and staffing costs for the POC troponin pathways, assuming a 5-year device life span, was $2.27 million for the pathway without prehospital discharge and $4.60 million for the pathway with prehospital discharge, incorporating virtual ED costs. In the decision tree model, total annual cost using prehospital point-of-care troponin and paramedic risk stratification was lower compared with existing care, both without prehospital discharge. The estimated annual statewide cost savings of prehospital risk stratification and troponin measurement was $6.45 million without using prehospital discharge and $42.84 to $71.84 million using prehospital discharge for low-risk patients.
Because prehospital POC troponin testing and paramedic risk stratification for patients with acute chest pain may result in substantial cost savings, the researchers urged policy makers to consider their findings, pending confirmation of the scenario in prospective studies.