An audit of rapid SARS-CoV-2 real-time reverse transcription-polymerase chain reaction (RT-PCR) test orders at a tertiary medical center reveals widespread inappropriate ordering and the need for better guidance for clinicians, a recent paper said.

A retrospective review of the first 500 orders for the rapid Xpert Express SARS-CoV-2 RT-PCR over two weeks found that 69.8% of the orders did not meet the institution lab’s indications for rapid testing. The indications included emergency surgery, emergent obstetric procedures, behavioral health admission, pediatric admissions, and discharge to skilled care facilities (J Appl Lab Med 2021; doi: 10.1093/jalm/jfab081).

The majority of inappropriate orders were indicated for acute emergency surgery. But 49% of patients with these orders never had surgery. Also, 79% of these orders came from the trauma or emergency departments and had no other indication for testing.

Orders were also inappropriate in about 77% of indicated obstetrics cases, 68% of indicated behavioral care cases, and 35% of cases of patients indicated for testing for discharge to skilled care facilities. In contrast, the researchers deemed tests for all pediatric indications appropriate.

Although the study did not examine specific reasons for inappropriate test orders, previous studies note that they often arise from providers’ lack of knowledge.

In the current study, inappropriate orders may have resulted from clinicians seeing a potential need for emergent surgery for traffic accidents and gunshot injuries, the researchers postulate. However, hospital guidelines direct clinicians to order SARS-CoV-2 tests only after patients are definitively scheduled for surgery.

The findings show an opportunity for laboratory stewardship, the researchers added. They suggested that the electronic health record could be used to give evidence for the indications and to educate clinicians to direct tests appropriately and flag or stop inappropriate orders.

Blood Test Proposed for Early Detection of Alzheimer’s Disease

Comprehensive profiling of the Alzheimer’s disease (AD) plasma proteome could serve as a foundation for a blood-based AD test, according to a recent paper.

The authors developed a scoring system that distinguishes AD patients from healthy people based on a biomarker panel with 19 plasma proteins. The panel and scoring system identified AD patients with more than 96% accuracy (Alzheimers Dement 2021; doi: 10.1002/alz.12369).

The researchers quantified 1,160 plasma proteins in a Chinese cohort of 106 patients with AD and 74 healthy controls via high-throughput proximity extension assay (PEA). They validated the results in an independent cohort. In the subgroup analysis, the researchers used plasma biomarkers for amyloid, tau, phosphorylated tau, and neurodegeneration as endophenotypes of AD.

The researchers found 429 dysregulated proteins in AD patients’ plasma. They selected 19 “hub” proteins as representative of the AD plasma protein profile: KLK4, CD8A, LIF-R, hK14, AOC3, GSAP, NELL1, GAMT, CD164, LGMN, VPS37A, VAMP5, NFKBIE, TMSB10, PRKCQ, PRDX1, CASP-3, CETN2, and LYN. These hub proteins formed the basis of the scoring system, which accurately classified clinical AD with area under the curve equal to 0.9690–0.9816.

Specific hub proteins showed disease-stage-dependent dysregulation, which can delineate AD stages, the researchers wrote. However, it remains unclear whether the biomarkers sufficiently capture the whole signature of the AD blood proteome.

Comprehensive profiling of the AD plasma proteome might help clarify the signatures of AD blood and disease staging, the researchers wrote. They called for prospective longitudinal studies of mild cognitive impairment, AD, and other neurodegenerative diseases to determine the panel’s specificity.

Possible Pancreatic Cancer Biomarker Proposed

A recent study suggested that the protein pentraxin 3 (PTX3) may be a specific diagnostic biomarker for pancreatic ductal adenocarcinoma (PDAC) (npj Precis Onc 2021; doi: 10.1038/s41698-021-00192-1).

Computed tomography (CT) scanning is usually used for diagnosis of pancreatic cancer in general. Although CT can detect the presence of a pancreatic mass, it cannot distinguish pancreatic cancer from other non-cancerous pancreatic diseases. This situation poses frequent diagnostic dilemmas in clinical practice and drives the need for biomarkers for early detection of PDAC.

The researchers measured serum PTX3 via an enzyme-linked immunosorbent assay in serum from 140 patients who donated blood when they were diagnosed with PTX3 and 127 controls who were either healthy volunteers or diagnosed with other conditions, including pancreatitis, intra-ductal papillary neoplasms, and gallstones.

The researchers determined that PTX3 concentration above 4.34 ng/mL had a sensitivity of 86%, specificity of 86%, positive predictive value of 97%, and likelihood ratio of 6.05 for PDAC. They add that this profile is superior to CA 19-9 and carcinoembryonic antigen (CEA) for detecting PDAC.

In in vitro and ex vivo analysis of PTX3 in human PDAC, cell lines and a transgenic mouse model for PDAC suggest that PTX3 is released from stroma cells, mainly in primary sclerosing cholangitis (PSC), the researchers added. In activated PSC, PTX3 secretion might possibly be downregulated by making PSC inactive using all-trans-retinoic acid (ATRA).

PTX3 organizes hyaluronan in conjunction with the gene TSG-6 and facilitates stellate and cancer cell invasion. A previous trial has shown PTX3 had no prognostic or predictive role in testing chemo-radiotherapy without stromal targeting. In another trial, stromal modulation by ATRA even at first dose is accompanied with serum PTX3 response in patients who later go on to demonstrate disease control, but not those in whom the disease progresses.

The researchers call for further testing of PTX3 in prospective, larger, multicenter cohorts and within clinical trials that target stroma.

Further analysis conducted by the team in human PDAC samples, pancreatic cancer cell lines, and a mouse model of pancreatic cancer confirmed that PTX3 is, indeed, released predominantly from pancreatic stellate cells when they have been activated in response to signals from cancer cells.

In a multicenter European cohort, the researchers measured PTX3 in serum from patients who donated blood when they were diagnosed and untreated for PDAC, as well as controls diagnosed with other conditions including pancreatitis, intraductal papillary neoplasms, and gallstones.

The researchers found that serum PTX3 levels about 4.34 ng/mL have a sensitivity of 86%, specificity of 86%, positive predictive value of 97%, and likelihood ratio of 6.05 for detection of PDAC. These characteristics are superior to those of serum 19-9 and CEA for detection of PDAC, the researchers wrote.