Despite links to cardiovascular risk, only 0.2% of Americans received an Lp(a) test over the past decade, raising concerns about access, equity, and preparedness for new therapies.
For lab leaders, the findings highlight both the challenges of uneven adoption and the opportunities to drive greater awareness, access, and equity as new therapies approach the market.
The study was published September 26 in Journal of the American College of Cardiology: Advances, used Epic Cosmos, a nationwide database encompassing over 300 million patient records from health systems in all 50 states. It marks the first time Epic Cosmos has been used at this scale within the University of California system, and the first study to assess national patterns of Lp(a) testing at this volume.
Lp(a) is a cholesterol particle in the blood that is almost entirely determined by genetics. Elevated levels, which affect about 20% of the US population, are linked to significantly higher risk of heart attack, stroke, and aortic valve disease. Unlike LDL cholesterol, Lp(a) does not respond to diet or lifestyle changes, and currently there are no widely available therapies to lower it—though several are in late-stage clinical trials.
US Testing Rates Remain Low
An article on the study stated, “They found that between 2015 and 2024, just 728,550 patients, representing only 0.2% of the US population, underwent Lp(a) testing. Testing increased from about 14,000 patients in 2015 to more than 300,000 in 2024, but overall rates remain far below what experts recommend for identifying individuals at risk.”
European nations are moving toward universal Lp(a) screening as a key early predictor of heart disease, while the U.S. continues to lag behind.
“By analyzing national data from over 300 million patients, we’ve uncovered how much work remains to bring Lp(a) testing into routine care,” said Mattheus Ramsis, MD, lead author and assistant professor of medicine at UC San Diego School of Medicine.
Mattheus Ramsis, MD, lead author and assistant professor of medicine at UC San Diego School of Medicine noted, “These insights give us a roadmap for expanding access and addressing gaps. We’re seeing a growing recognition among clinicians of the importance of Lp(a) testing, but the low overall testing rates and regional imbalances highlight how much further we need to go. Broader awareness and access to testing could make the difference between catching disease early and missing an opportunity to prevent heart attacks and strokes, ensuring that all patients benefit from emerging therapies.” (Photo credit: UC San Diego Division of Cardiovascular Medicine)
Testing Patterns
The UC San Diego study found stark inequities in testing patterns. Adults aged 50 to 65 were most likely to be tested, and testing was nearly equal between men and women. But less than 10% of patients tested were Black and only 7% were Hispanic or Latino, despite both groups being disproportionately impacted by cardiovascular disease.
“We’re seeing a growing recognition among clinicians of the importance of Lp(a) testing, but the low overall testing rates and regional imbalances highlight how much further we need to go,” Ramsis said. “Broader awareness and access to testing could make the difference between catching disease early and missing an opportunity to prevent heart attacks and strokes, ensuring that all patients benefit from emerging therapies.”
Geographic disparities also stood out. California, Ohio, and Texas accounted for more than a quarter of all tests nationwide, while some states saw almost no uptake. Researchers say this uneven adoption underscores the need for clearer national guidelines and more consistent payer coverage to make Lp(a) testing accessible everywhere.
The study also noted that there was a shift in how tests are being conducted. The article said, “In 2015, most measurements used older ‘mass-based’ assays, which measure the total weight of Lipoprotein(a) in a blood sample. However, by 2024, two-thirds of tests were performed using the more accurate molar assays, in line with evolving clinical guidelines. Molar assays measure the actual number of Lp(a) particles in a person’s bloodstream to assess cardiovascular disease risk, rather than just the mass of particles.”
Co-author Ehtisham Mahmud, MD, professor of medicine and chief of the Division of Cardiovascular Medicine at UC San Diego, stressed the importance of laboratories in expanding adoption.
Mahmud commented, “The rise in testing is encouraging, but we are still far from where we need to be. If we want to close the gaps in cardiovascular risk assessment, especially in underserved communities, we need broader education, clearer guidelines and consistent insurance coverage for Lp(a) testing.”
For laboratory leaders, one of the most important steps in closing the gap on Lp(a) testing is proactive communication with physicians. Many clinicians may not be fully aware of the latest guidelines recommending at least one lifetime Lp(a) test for adults, or of the shift from mass-based to molar assays that better assess cardiovascular risk.
Lab leaders can play a central role by educating providers on when and why to order the test, sharing local testing capacity, and emphasizing how results may guide risk stratification as new therapies reach the market. By positioning themselves as trusted partners in cardiovascular prevention, labs can help physicians incorporate Lp(a) testing into routine practice, expand access to high-risk patients, and ultimately strengthen patient outcomes.
Cytovale’s IntelliSep test helped the hospital improve compliance with the controversial SEP-1 measure.
In a study of patients at an emergency department in Baton Rouge, Louisiana, a blood test designed for early detection of sepsis helped improve compliance with a controversial quality measure implemented by the US Centers for Medicare & Medicaid Services (CMS). Researchers reported that a treatment protocol incorporating Cytovale’s IntelliSep test increased the rate of compliance with SEP-1, a set of interventions recommended by CMS when a patient presents severe sepsis or septic shock. The study, which was funded by Cytovale, was presented Sept. 7 at the American College of Emergency Physicians (ACEP) conference in Salt Lake City.
“The clinical criteria for the SEP-1 bundle may not always support identification of sepsis early on in the progression of disease,” said principal investigator Hollis O’Neal, MD, medical director of research at Our Lady of the Lake Regional Medical Center (OLOLRMC) in Baton Rouge, in a press release from Cytovale. “IntelliSep, which looks at a patient’s immune dysregulation, has been a critical tool in helping us quickly identify patients during our initial ED triage who otherwise didn’t ‘look septic.’”
The Mayo Clinic describes sepsis as “a serious condition in which the body responds improperly to an infection. The infection-fighting processes turn on the body, causing the organs to work poorly.” In some cases, it can lead to septic shock, “a dramatic drop in blood pressure that can damage the lungs, kidneys, liver and other organs.”
A 2021 task force report from the Infectious Diseases Society of America (IDSA) stated that sepsis “is a major cause of hospital death in the United States and is associated with over 850,000 annual emergency department visits.” The report also noted “the inherent difficulty in establishing the early diagnosis of sepsis.”
The IntelliSep Test
Cytovale, based in South San Francisco, Calif., was founded in 2013 by researchers from MIT and UCLA. IntelliSep is the company’s primary product.
As explained by the company, sepsis causes changes to the biomechanics of white blood cells, including size, deformability, and how they behave in fluid.
In the IntelliSep test, a blood sample is loaded into a device that uses hydrodynamic forces, high-resolution imaging, and computer vision to analyze the cells’ biomechanical properties. The system then presents a numeric value that indicates if the patient has a low, medium, or high probability of sepsis.
The test takes about eight minutes to run. Cytovale cautions that “all results should be interpreted in the context of the other clinical observations and laboratory test results for the patient.”
The US Food and Drug Administration issued a 510(k) clearance for the test in January 2023.
Study Shows Improved Compliance
The OLOLRMC study, which involved 598 patients, measured the impact of the test on compliance the SEP-1 guidelines, which specify how sepsis cases should be managed. For example, clinicians are advised to measure a patient’s lactate level, collect a blood culture, and administer antibiotics within three hours after presentation of severe sepsis.
In July 2024, when the hospital began incorporating the test, SEP-1 compliance was 61.2%, the authors reported. By September, the rate had increased to 72.5%, and it increased to 78.9% by December. They reported that the test enabled clinicians to begin treating the highest-risk patients earlier, increasing the number who received recommended interventions within the three-hour window mandated by SEP-1.
“Unlike traditional approaches that may boost SEP-1 performance by broadly applying sepsis protocols—often at the cost of overtreatment—we integrated IntelliSep into our sepsis protocol to gain objective insight into sepsis risk, ensuring we deliver the SEP-1 bundle to the right patients from the start,” said study co-author Christopher Thomas, MD, of Our Lady Health System, in a press release from Cytovale. “This approach yielded significant results, enabling OLOL to achieve meaningful compliance gains in a short time.” (Photo credit: LSU Health Sciences Center)
Questioning SEP-1
The SEP-1 guidelines are controversial. CMS contends that they reduce hospital mortality. However, in 2023, a coalition of professional societies—including the IDSA, Society of Hospital Medicine, and American College of Emergency Physicians—urged the agency to retire SEP-1.
“The SEP-1 measure does not take into account that many serious conditions present in a similar fashion to sepsis,” they argued. “Pushing clinicians to treat all these patients as if they have sepsis leads to overuse of broad-spectrum antibiotics, which can be harmful to patients who are not infected, those who are infected with viruses rather than bacteria and those who could safely be treated with narrower-spectrum antibiotics.”
They also cited studies showing that SEP-1 has not improved patient outcomes. That position was bolstered earlier this year as a systematic literature review in Annals of Internal Medicine“found no moderate- or high-level evidence to support that compliance with or implementation of SEP-1 was associated with sepsis mortality,” according to the authors.
As noted in the Substack publication PulmCCM, CMS introduced SEP-1 in 2015 as a pay-for-reporting measure, meaning that hospitals were required to report compliance rates, but were not penalized for non-compliance. However, in 2023, CMS proposed making it a pay-for-performance measure as part of the Hospital Value-Based Purchasing Program. As a result, beginning in 2026, payments to hospitals will be adjusted based on their SEP-1 compliance rates.
New CAP cancer protocol updates bring key biomarker changes—what lab leaders need to know to stay compliant, current, and clinically aligned.
As a lab leader, ensuring your team remains aligned with the most current standards is critical to maintaining diagnostic excellence and meeting clinical demands. The College of American Pathologists (CAP) recently released its Q3 updates to 10 cancer protocols, with a strong focus on biomarker revisions that are central to patient care and treatment planning. These updates reflect CAP’s commitment to “accurate, standardized cancer reporting” and alignment with evolving guidelines from the American Joint Committee on Cancer (AJCC) and the World Health Organization (WHO).
Key Changes in Biomarker Reporting
One of the most impactful updates is in the Lung, Biomarker Protocol, which now reflects the growing role of precision oncology. CAP has expanded molecular profiling to include updates on BRAF, NTRK, NRG1, and Tumor Mutational Burden. These enhancements are designed to support broader and more relevant genomic testing. For labs striving to deliver comprehensive molecular diagnostics, this is a significant shift that calls for potential workflow and test menu evaluations.
In the GYN, Biomarker Protocol, CAP introduces more flexibility while tightening standards where necessary:
“All immunohistochemical (IHC) tests are now optional”, a change from the previous requirement, offering labs greater discretion based on case specifics.
However, for HER2 testing, there’s a new required element: “HER2 In Situ Hybridization Testing Status is now a required element when reporting Equivocal (score 2+) protein overexpression in HER2 Status for Trastuzumab use.” This ensures precise treatment decisions, particularly in borderline cases.
Additionally, CAP now mandates reporting the “MLH1 Promoter Methylation Analysis Status” when there’s a loss of nuclear expression of MLH1 and PMS2 in MMR IHC interpretation—an important step toward standardizing Lynch syndrome assessment.
Photo credit: “Cancer” by davis.steve32 is licensed under CC BY 2.0. To view a copy of this license, visit https://creativecommons.org/licenses/by/2.0/?ref=openverse.
General Biomarker Reporting Enhancements
The update also revises General IHC Quantitative Biomarkers, providing more comprehensive and customizable reporting tools. Newly introduced optional data elements include:
Cold Ischemic Time
Fixative
Fixation Time
Membranous Staining Intensity
These additions allow labs to include more detailed pre-analytic and analytic variables when needed. CAP also improves clarity by offering expanded reporting options for internal controls and removing ambiguity. Notably, they have “removed the ‘(indeterminate)’ parenthetical for ‘Cannot be determined’ answers,” which better distinguishes between uncertain and genuinely unreportable results.
Beyond Biomarkers: Protocol Revisions Across Specialties
The Q3 update extends beyond biomarkers, with revised protocols in several high-impact areas:
Lung resection protocols
Ophthalmic cancers
Central nervous system tumors
Hematologic malignancies
These changes aim to integrate the latest research and clinical consensus into routine cancer diagnostics. As always, a full Summary of Revisions is available at cap.org.
What This Means for Lab Leaders
For lab directors and pathology team leaders, these updates aren’t just technical, they’re strategic. Implementing them ensures compliance, enhances diagnostic accuracy, and positions your lab as a partner in precision oncology. Leaders should:
Review and update standard operating procedures considering new required elements.
Educate pathologists and molecular staff about changes, especially those affecting interpretation and reporting.
Coordinate with IT or LIS teams to integrate optional data fields where useful.
In short, staying current with CAP protocols isn’t just about meeting accreditation standards, it’s about delivering the best possible care through high-quality diagnostics.
WHO is developing its first global guidelines on multiplex testing for HIV, hepatitis, and STIs, offering lab leaders a framework to optimize diagnostics, streamline workflows, and lead the shift toward integrated, multi-disease testing.
As diagnostic technologies rapidly evolve and healthcare systems shift toward integrated service delivery, laboratory leaders are at the forefront of implementing efficient, multi-disease testing strategies.
In a landmark move, the World Health Organization (WHO) has convened a Guideline Development Group (GDG) to develop its first-ever evidence-based recommendations on multiplex testing, a method that enables simultaneous detection of HIV, viral hepatitis, and STIs from a single sample. This initiative will establish foundational principles for integration, resource prioritization, and diagnostic efficiency, offering lab professionals critical guidance to shape the future of testing across diseases.
The GDG, comprised of international experts and stakeholders, will provide evidence-based recommendations to support integrated, people-centered diagnostic strategies.
As global health systems shift toward more integrated service delivery, multiplex testing is emerging as a practical tool for increasing diagnostic access, streamlining care, and maximizing limited resources, particularly in low- and middle-income countries, where testing gaps remain significant.
“Access to timely and accurate diagnostic testing is essential for the prevention, detection, and management of HIV, viral hepatitis and STIs,” WHO stated in its announcement. “Multiplex testing has emerged as a promising strategy to improve efficiency, expand testing coverage across diseases, and enhance cost-effectiveness.”
A First-of-Its-Kind Guideline
This is the first WHO guideline to explicitly address multiplex testing using the most up-to-date evidence. While the focus will be on HIV, viral hepatitis, and STIs, the guidelines aim to establish critical principles for integration that can be extended to other disease areas over time.
“This guideline will provide critical principles for integration that drive public health impact and chart the course for further multi-disease testing approaches,” WHO noted.
Photo credit: “World Health Organization Flag” by United States Mission Geneva is licensed under CC BY 2.0. To view a copy of this license, visit https://creativecommons.org/licenses/by/2.0/?ref=openverse.
The GDG will address both provider-based testing and self-testing, recognizing the growing role of community-led and patient-driven diagnostics. Key issues on the agenda include how to prioritize limited testing resources, ensure quality assurance, and optimize public health outcomes through integrated diagnostic models.
Guideline Development Group: Global, Inclusive, Independent
The GDG is composed of members from all WHO regions, selected based on their technical expertise, field experience, and perspectives as either implementers or members of affected communities. Importantly, all members participate in their individual capacities and not as representatives of any affiliated organizations.
“In accordance with WHO guidelines for developing recommendations, the GDG is composed of members from all WHO regions, serving in their individual capacities,” the organization explained. “Members do not receive financial compensation for their contributions to this process.”
The GDG includes program managers, healthcare providers, researchers, and community advocates, reflecting the full spectrum of stakeholders involved in diagnostic service delivery. Their diverse backgrounds are intended to ensure that the guidelines are evidence-informed, practical, and contextually relevant across settings.
A virtual meeting is scheduled for November 4-5, 2025, during which the group will discuss evidence, identify priority recommendations, and finalize key principles around multiplex testing and integration.
WHO Opens Public Comment Period
To promote transparency and inclusivity, WHO has opened a public comment period and is inviting feedback on the composition of the GDG. Stakeholders, organizations, and individuals can review member biographies and submit comments via email to hiv-aids@who.int by September 29, 2025.
The upcoming guideline represents a significant step in advancing integrated diagnostics and expanding access to care, particularly in resource-limited settings. By combining clinical evidence with real-world insights, WHO aims to provide countries and implementers with practical, scalable recommendations that improve testing coverage and disease detection at all levels of the health system.
As testing technologies evolve and the demand for multi-disease platforms grows, this guideline may serve as a blueprint for future diagnostic integration efforts, laying the foundation for efficient, patient-centered, and cost-effective care delivery worldwide.
A UCLA microbiology lab used whole-genome sequencing to trace a carbapenem-resistant Pseudomonas outbreak to a single ICU sink, revealing how biofilm and plumbing can silently harbor superbugs.
A routine culture from an ICU patient at UCLA Health sparked an investigation that ultimately uncovered a silent, domestic outbreak of a highly resistant strain of Pseudomonas aeruginosa. The discovery was led by the Molecular Microbiology and Pathogen Genomics Laboratory and highlights the critical role clinical laboratories play in outbreak detection, antimicrobial resistance surveillance, and environmental tracking.
The initial isolate appeared typical: P. aeruginosa, a common hospital-associated pathogen. But further analysis revealed something more troubling, the presence of NDM-1 (New Delhi metallo-β-lactamase), an enzyme that breaks down carbapenems and other powerful beta-lactam antibiotics, rendering them ineffective.
“This was the first time we’d ever seen an NDM-1-producing Pseudomonas strain in our hospital—and in a patient with no international travel,” said Shangxin Yang, PhD, director of UCLA Health’s Molecular Microbiology and Pathogen Genomics Laboratory.
Shangxin Yang, PhD, director of UCLA Health’s Molecular Microbiology and Pathogen Genomics Laboratory noted, “While NDM-1 is prevalent in Asia, Europe and the Middle East, it remains rare in the United States. That’s when we knew this wasn’t imported. This was something domestic—and very concerning.” (Photo credit: UCLA)
Sporadic Cases, Elusive Source
Over the next 18 months, seven additional patients were identified with the same rare resistance pattern. The cases were sporadic—spread across time and units—and did not follow conventional outbreak patterns, complicating source identification.
In collaboration with UCLA Health’s infection prevention team, the lab launched a detailed investigation. Routine epidemiologic methods failed to identify commonalities between the cases. Shared equipment, staffing patterns, and care protocols were ruled out. With limited leads, the microbiology team turned to whole-genome sequencing (WGS).
Whole-Genome Sequencing Connects the Dots
WGS became the turning point. By sequencing all eight patient isolates and comparing them to environmental samples, Yang’s lab determined that seven of the eight clinical isolates and two environmental strains shared an almost identical genomic profile. Only one isolate, from a patient previously treated in Iran, was genetically distinct.
“Whole-genome sequencing gave us the clarity we needed,” said Yang. “It allowed us to move from hypothesis to high-resolution confirmation—pinpointing the genetic relatedness of these organisms with certainty.”
The team had uncovered a clonal outbreak of NDM-1-producing P. aeruginosa, likely stemming from a single environmental reservoir.
Unexpected Reservoir: An ICU Sink
During a third round of environmental testing, the lab isolated the same NDM-1-producing strain from a contaminated sink drain and P-trap in one ICU room. Notably, two of the eight patients had been admitted to that room more than a year apart.
The persistence of the organism was attributed to biofilm formation in the sink plumbing. Pseudomonas is known for forming robust biofilms that adhere to moist surfaces and resist standard disinfection methods.
“This wasn’t just about surface contamination,” said Yang. “This was a deeply embedded reservoir that conventional cleaning protocols couldn’t touch.”
Lab-Driven Response and Mitigation
Once the lab identified the environmental source, targeted interventions were put in place:
Weekly disinfection of ICU sinks using Virasept, a biofilm-effective agent
Plumbing replacement, including P-trap components known to harbor persistent biofilms
Engineering modifications to faucet angles to reduce splash-back and droplet spread
Expanded environmental surveillance to monitor other sinks for colonization
The lab continued to monitor the situation post-intervention, and no further cases of NDM-1-producing P. aeruginosa have been identified since the changes were implemented.
Lessons Learned
This case reinforces the value of whole-genome sequencing in resolving complex outbreaks, linking patient isolates to an environmental source that traditional methods missed. It highlights the need to include plumbing and other biofilm-prone areas in environmental sampling. Most importantly, it shows how microbiology labs through genomic, phenotypic, and molecular tools can lead outbreak investigations, especially when paired with strong cross-department collaboration.
“This is a clear example of the power of the clinical lab when genomic tools and environmental surveillance are used strategically,” said Yang. “Without WGS, this would have remained an unsolved mystery.”
Bloomberg reports Siemens is in early discussions with Blackstone, KKR, and others about selling its diagnostics division. What could that mean for the future of in vitro diagnostics and market dynamics?
Bloomberg speculated in a recent article that Siemens has been holding “exploratory discussions” with some of the largest private equity firms regarding a sale of its diagnostics arm.
The possible divestment of Siemens Healthineers’ diagnostics business is more than just a corporate strategy shift. For laboratory leaders, it could signal major changes for clinical laboratories worldwide. As one of the largest players in in vitro diagnostics, Siemens has long been a key supplier of systems and reagents used to process millions of patient samples.
The report that Siemens is in early discussions to sell this division to private equity firms raises critical questions for lab leaders: What could this mean for continuity, innovation, pricing, and support? As healthcare systems globally face pressure to do more with less, any disruption or optimization in lab operations can have effects on patient care and operational stability.
In the most recent edition of The Dark Report, Siemens was ranked as #5 (tied with BD) in its article on the top IVD companies by diagnostic revenue.
Private Equity Firms Reportedly in Early Talks
Bloomberg said that sources, who do not want to be identified, noted that Blackstone Inc., CVC Capital Partners Plc, and KKR & Co. were in “early talks” with Siemens and other individuals commented that Montagu had previously expressed interest.
The article explained, “The diagnostics unit could be valued at more than €6 billion ($7 billion) in a transaction, according to some of the people. Advisers could be appointed at a later stage if discussions proceed into formal stages, the people said.”
The sources noted to Bloomberg that there was no guarantee that any of the discussions would come to fruition and representatives from Siemens Healthineers, Blackstone, CVC, KKR, and Montagu declined to comment to Bloomberg.
Photo credit: RonaldCandonga
The article added, “Based in Erlangen, Bavaria, Siemens Healthineers started a review of the diagnostics business more than two years ago. The in vitro diagnostics operations test samples of blood and tissue to identify diseases and infections. The imaging division and the Varian unit that focuses on cancer-care technologies wouldn’t be part of any sale.”
As of Sept. 10, shares of Siemens Healthineers gained as much as 3.6%—the largest intraday advance since May 12, after Bloomberg News reported on the matter. “The stock has still fallen about 6% this year, giving the company a market value of around €54 billion,” the article added. “The company’s largest shareholder is German engineering group Siemens AG, which has a stake of roughly 71%, according to data compiled by Bloomberg.”
Strategic Updates Expected at Capital Markets Day
Siemens Healthineers is set to host its Capital Markets Day on November 17, an event typically used to present its business strategy and financial targets. In February, Siemens reduced its stake in Healthineers through a €1.4 billion share placement. The company is currently reviewing its remaining holdings in Healthineers and intends to provide a strategic update to investors in December.
On Sept. 15, Finimize reported that Bank of America maintains its buy rating and €65 target for Siemens Healthineers, citing strong demand, increased hospital spending in the US and Europe, and potential growth in China by 2026.
A possible sale of its diagnostics division, that is currently a drag on growth and margins, could streamline the business and boost profitability. According to Finimize, management says the sale wouldn’t affect core areas like imaging and radiotherapy. Investors are looking at this situation closely for strategic updates at the aforementioned upcoming Capital Markets Day and full-year results.
For investors, selling diagnostics could simplify the company, lift growth, and fuel share price momentum. For the sector, Siemens’ strategy shift could influence other medtech firms aiming for leaner options and rising global healthcare demand.
IVD Market in Flux
In August, TheDark Reportreported that at an unusually fast pace, announced in February and finalized by July, BD’s Biosciences & Diagnostics Solutions business entered a definitive agreement to combine with Waters.
For laboratory leaders, the potential sale of Siemens’ diagnostics division, and perhaps the recent news about BD and Waters, is a development that could reshape the diagnostic supplier landscape. Whether it leads to improved focus and investment under new ownership or introduces uncertainty around product lines and service levels, it’s essential to stay informed. Labs should be proactive in engaging with vendor representatives, assessing supply chain resilience, and preparing for potential shifts. This is a pivotal moment where business decisions at the top could ripple directly into the day-to-day realities of the lab.
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