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Change Healthcare Cyberattack Disrupts Pharmacy Order Processing for Healthcare Providers Nationwide

Initially thought to be an attack by a nation-state, actual culprit turned out to be a known ransomware group and each day brings new revelations about the cyberattack

Fallout continues from cyberattack on Change Healthcare, the revenue cycle management (RCM) company that is a business unit of Optum, itself a division of UnitedHealth Group. Recent news accounts say providers are losing an estimated $100 million per day because they cannot submit claims to Change Healthcare nor receive reimbursement for these claims. 

The cyberattack took place on February 21. The following day, UnitedHealth Group filed a Material Cybersecurity Incidents report (form 8-K) with the US Securities and Exchange Commission (SEC) in which it stated it had “identified a suspected nation-state associated cybersecurity threat actor [that] had gained access to some of the Change Healthcare information technology systems.”

A few days later the real identity of the threat actor was revealed to be a ransomware group known as “BlackCat” or “ALPHV,” according to Reuters.

Change Healthcare of Nashville, Tenn., is “one of the largest commercial prescription processors in the US,” Healthcare Dive reported, adding that hospitals, pharmacies, and military facilities had difficulty transmitting prescriptions “as a result of the outage.”

 Change Healthcare handles about 15 billion payments each year.

According to a Change Healthcare statement, the company “became aware of the outside threat” and “took immediate action to disconnect Change Healthcare’s systems to prevent further impact.”

Change Healthcare has provided a website where parties that have been affected by the cyberattack can find assistance and updated information on Change’s response to the intrusion and theft of its data.

“The fallout is only starting to happen now. It will get worse for consumers,” Andrew Newman (above), founder and Chief Technology Officer, ReasonLabs, told FOX Business, adding, “We know that the likely destination for [the Change Healthcare] data is the Dark Web, where BlackCat will auction it all off to the highest bidder. From there, consumers could expect to suffer from things like identity theft, credit score downgrades, and more.” Clinical laboratories are also targets of cyberattacks due to the large amount of private patient data stored on their laboratory information systems. (Photo copyright: ReasonLabs.)

Millions of Records May be in Wrong Hands

Reuters reported that ALPHV/BlackCat admitted it “stole millions of sensitive records, including medical insurance and health data from the company.” 

The ransomware group has been focusing its attacks on healthcare with 70 incidents since December, according to federal agencies. 

“The healthcare sector has been the most commonly victimized. This is likely in response to the ALPHV BlackCat administrator’s post encouraging its affiliates to target hospitals after operational action against the group and its infrastructure in early December 2023,” noted a joint statement from the federal Cybersecurity and Infrastructure Security Agency (CISA), Federal Bureau of Investigation (FBI), and the Department of Health and Human Services (HHS).

AHA Urges Disrupted Hospitals to Disconnect from Optum

In an AHA Cybersecurity Advisory, the American Hospital Association recommended that affected providers “consider disconnection from Optum until it is independently deemed safe to reconnect to Optum.”

In a letter to HHS, AHA warned, “Change Healthcare’s downed systems will have an immediate adverse impact on hospital finances. … Their interrupted technology controls providers’ ability to process claims for payment, patient billing, and patient cost estimation services.”

“My understanding is Change/Optum touches almost every hospital in the US in one way or another,” John Riggi, AHA’s National Advisor for Cybersecurity and Risk, told Chief Healthcare Executive. “It has sector wide impact in potential risk. So, really, this is an attack on the entire sector.” Riggi spent nearly 30 years with the FBI.

Some physician practices may also have been impacted by the Change Healthcare cyberattack, according to the Medical Group Management Association (MGMA). In a letter to HHS, MGMA described negative changes in processes at doctors’ offices. They include delays in paper and electronic statements “for the duration of the outage.”

In addition, “prescriptions are being called into pharmacies instead of being electronically sent, so patients’ insurance information cannot be verified by pharmacies, and [the patients] are forced to self-pay or go without necessary medication.”

Here are “just a few of the consequences medical groups have felt” since the Change Healthcare cyberattack, according to the MGMA:

  • Substantial billing and cash flow disruptions, such as a lack of electronic claims processing. Both paper and electronic statements have been delayed. Some groups have been without any outgoing charges or incoming payments for the duration of the outage.
  • Limited or no electronic remittance advice from health plans. Groups are having to manually pull and post from payer portals.
  • Prior authorization submissions have been rejected or have not been transmittable at all. This further exacerbates what is routinely ranked the number one regulatory burden by medical groups and jeopardizes patient care.
  • Groups have been unable to perform eligibility checks for patients.
  • Many electronic prescriptions have not been transmitted, resulting in call-in prescriptions to pharmacies or paper prescriptions for patients. Subsequently, patients’ insurance information cannot be verified by pharmacies, and they are forced to self-pay or go without necessary medication.
  • Lack of connectivity to important data infrastructure needed for success in value-based care arrangements, and other health information technology disruptions.

Medical laboratory leaders and pathologists are advised to consult with their colleagues in IT and cybersecurity on how to best prevent ransomware attacks. Labs hold vast amount of private patient information. Recent incidents suggest more steps and strategies may be needed to protect laboratory information systems and patient data.

—Donna Marie Pocius

Related Information:

UnitedHealth Suspects “Nation-state” Behind Change Cyberattack

UnitedHealth Says ‘Blackcat’ Ransomware Group Behind Hack At Tech Unit

UnitedHealth Hackers Say They Stole ‘Millions’ of Records, then Delete Statement

US SEC Form 8-K

Change Healthcare Incident Status

Information on the Change Healthcare Cyber Response

UnitedHealth Confirms BlackCat Group Behind Recent Cybersecurity Attack

CISA Cybersecurity Advisory

Hackers Behind UnitedHealth Unit Cyberattack Reportedly Identified

Hospitals Affected by Cyberattack of UnitedHealth Subsidiary

UnitedHealth Group’s Change Healthcare Experiencing Cyberattack Could Impact Healthcare Providers

AHA Letter to HHS: Implications Change Healthcare Cyberattack

MGMA Letter to HHS

The Change Healthcare Cyberattack Is Still Impacting Pharmacies. It’s a Bigger Deal Than You Think

BMJ Oncology Study Shows 79% Increase in Cancer among People under 50 Years of Age

Findings suggest new medical guidelines may be needed to determine when to perform clinical laboratory cancer screenings on people under 50

From 1990-2019, new diagnoses of early-onset cancer in individuals under 50 years of age increased by 79%, according to a British Medical Journal (BMJ) news release describing research published last year in BMJ Oncology. The question for anatomic pathology laboratories to consider is, why are more people under 50 being diagnosed with cancer than in earlier years? And do medical guidelines need to be changed to allow more cancer screening for individuals under 50-years old?

This new revelation challenges previously held beliefs about the number of younger adults under 50 experiencing early-onset cancer. Patients can sometimes miss symptoms by attributing them to a more benign condition.

“While cancer tends to be more common in older people, the evidence suggests that cases among the under 50s have been rising in many parts of the world since the 1990s. But most of these studies have focused on regional and national differences; and few have looked at the issue from a global perspective or the risk factors for younger adults, say the researchers. In a bid to plug these knowledge gaps, they drew on data from the Global Burden of Disease 2019 Study for 29 cancers in 204 countries and regions,” the BMJ news release states.

According to the news release, “Breast cancer accounted for the highest number of ‘early-onset’ cases in this age group in 2019. But cancers of the windpipe (nasopharynx) and prostate have risen the fastest since 1990, the analysis reveals. Cancers exacting the heaviest death toll and compromising health the most among younger adults in 2019 were those of the breast, windpipe, lung, bowel, and stomach.”

Although these statistics are being seen worldwide, the highest rates are in North America, Australasia, and Western Europe. However, high death rates due to cancer are also being seen in Eastern Europe, Central Asia, and Oceania. Economic disparities in the latter geographical regions may account for both fewer diagnoses and higher death rates.

“And in low to middle income countries, early onset cancer had a much greater impact on women than on men, in terms of both deaths and subsequent poor health,” the BMJ news release noted.

In an editorial they published in BMJ Oncology on the study findings, Ashleigh Hamilton, PhD (left), Academic Clinical Lecturer, and Helen Coleman, PhD (right), Professor, School of Medicine, Dentistry and Biomedical Sciences, both at the Center for Public Health at Queen’s University Belfast in the UK wrote, “The epidemiological landscape of cancer incidence is changing. … Prevention and early detection measures are urgently required, along with identifying optimal treatment strategies for early-onset cancers, which should include a holistic approach addressing the unique supportive care needs of younger patients.” Anatomic pathology laboratories will play an important role in diagnosing and treating younger cancer patients. (Photo copyrights: Queen’s University Belfast.)

What Caused the Increase?

“It’s such an important question, and it points to the need for more research in all kinds of domains—in population science, behavioral health, public health, and basic science as well,” said medical oncologist Veda Giri, MD, Professor of Internal Medicine, Yale School of Medicine, in a news release. Giri directs the Yale Cancer Center Early-Onset Cancer Program at Smilow Cancer Hospital.

Although experts are still trying to determine exactly where these cases are coming from, signs point to both genetic and lifestyle factors, the BMJ news releases noted. Tobacco and alcohol use, diets high in cholesterol and sodium, and physical inactivity are all lifestyle risk factors. Experts recommend a healthy diet and exercise routine with minimal alcohol consumption.

As for family history? “We’re beginning to recognize that family history is very important,” says Jeremy Kortmansky, MD, also a Yale Medicine medical oncologist.

According to CNN Health, these rates of early-onset cancer are more common in female patients, with rates going up an average of 0.67% each year.

“For young women who have a significant family history of cancer in the family, we are starting to refer them to a high-risk clinic—even if the cancer in their family is not breast cancer,” Kortmansky noted.

Doctors advise patients to implement healthy habits into their lives, not ignore symptoms, advocate for themselves, and be aware of their family history. Cancer patients may be prescribed cancer treatments at a much earlier age. Medical guidelines for patients may continue to shift and change. And oncologists may be incorporating alternative therapies to help younger patients deal with the shock of their diagnosis.

Will Cancer Rates Continue to Rise?

“Based on the observed trends for the past three decades, the researchers estimate that the global number of new early-onset cancer cases and associated deaths will rise by a further 31% and 21% respectively in 2030, with those in their 40s the most at risk,” the BMJ news release noted.

In an editorial they penned for BMJ Oncology on the findings of the cancer study titled, “Shifting Tides: The Rising Tide of Early-Onset Cancers Demands Attention,” Ashleigh Hamilton, PhD, Academic Clinical Lecturer, and Helen Coleman, PhD, Professor, School of Medicine, Dentistry and Biomedical Sciences, both at the Center for Public Health at Queen’s University Belfast in the UK wrote, “Full understanding of the reasons driving the observed trends remains elusive, although lifestyle factors are likely contributing, and novel areas of research such as antibiotic usage, the gut microbiome, outdoor air pollution, and early life exposures are being explored. It is crucial that we better understand the underlying reasons for the increase in early-onset cancers, in order to inform prevention strategies.”

Clinical laboratories should be aware of these findings and the changing landscape of cancer screenings, as they will play a key role in diagnoses. Younger patients may be advocating for cancer screenings and doctors may be ordering them depending on the patient’s symptoms and family history. Anatomic pathology professionals should expect new guidelines when it comes to cancer diagnostics and treatment.

—Ashley Croce

Related Information:

Global Surge in Cancers among the Under 50s over Past Three Decades

Shifting Tides: The Rising Tide of Early-Onset Cancers Demands Attention

Global Trends in Incidence, Death, Burden and Risk Factors of Early-Onset Cancer from 1990 to 2019

Cancer Diagnosis Rates are Going up in Younger Adults, Study Finds, Driven Largely By Rises in Women and People in Their 30s

Early Onset Cancer Cases Rise 80% in Past Three Decades, BMJ Survey Finds

Cancer in Younger People Is on the Rise: Knowing Your Family History Can Help

Study Points to Big Surge in Under-50 Cancer Cases

Researchers See Surge in Number of People under 50 Diagnosed with Cancer

New Federal Rules on Sepsis Treatment Could Cost Hospitals Millions of Dollars in Medicare Reimbursements

Some hospital organizations are pushing back, stating that the new regulations are ‘too rigid’ and interfere with doctors’ treatment of patients

In August, the Biden administration finalized provisions for hospitals to meet specific treatment metrics for all patients with suspected sepsis. Hospitals that fail to meet these requirements risk the potential loss of millions of dollars in Medicare reimbursements annually. This new federal rule did not go over well with some in the hospital industry.

Sepsis kills about 350,000 people every year. One in three people who contract the deadly blood infection in hospitals die, according to the Centers for Disease Control and Prevention (CDC). Thus, the federal government has once again implemented a final rule that requires hospitals, clinical laboratories, and medical providers to take immediate actions to diagnose and treat sepsis patients.

The effort has elicited pushback from several healthcare organizations that say the measure is “too rigid” and “does not allow clinicians flexibility to determine how recommendations should apply to their specific patients,” according to Becker’s Hospital Review.

The quality measures are known as the Severe Sepsis/Septic Shock Early Management Bundle (SEP-1). The regulation compels doctors and clinical laboratories to:

  • Perform blood tests within a specific period of time to look for biomarkers in patients that may indicate sepsis, and to
  • Administer antibiotics within three hours after a possible case is identified.

It also mandates that certain other tests are performed, and intravenous fluids administered, to prevent blood pressure from dipping to dangerously low levels. 

“These are core things that everyone should do every time they see a septic patient,” said Steven Simpson, MD, Professor of medicine at the University of Kansas told Fierce Healthcare. Simpson is also the chairman of the Sepsis Alliance, an advocacy group that works to battle sepsis. 

Simpson believes there is enough evidence to prove that the SEP-1 guidelines result in improved patient care and outcomes and should be enforced.

“It is quite clear that this works better than what was present before, which was nothing,” he said. “If the current sepsis mortality rate could be cut by even 5%, we could save a lot of lives. Before, even if you were reporting 0% compliance, you didn’t lose your money. Now you actually have to do it,” Simpson noted.

Chanu Rhee, MD

“We are encouraged by the increased attention to sepsis and support CMS’ creation of a sepsis mortality measure that will encourage hospitals to pay more attention to the full breadth of sepsis care,” Chanu Rhee, MD (above), Infectious Disease/Critical Care Physician and Associate Hospital Epidemiologist at Brigham and Women’s Hospital told Healthcare Finance. The new rule, however, requires doctors and medical laboratories to conduct tests and administer antibiotic treatment sooner than many healthcare providers deem wise. (Photo copyright: Brigham and Women’s Hospital.)

Healthcare Organizations Pushback against Final Rule

The recent final rule builds on previous federal efforts to combat sepsis. In 2015, the Centers for Medicare and Medicaid Services (CMS) first began attempting to reduce sepsis deaths with the implementation of SEP-1. That final rule updated the Medicare payment policies and rates under the Inpatient Prospective Payment System (IPPS) and Long-Term Care Hospitals Prospective Payment System (LTCH PPS).

Even then the rule elicited a response from the American Hospital Association (AHA), the Infectious Disease Society of America (IDSA), American College of Emergency Physicians (ACEP), the Society of Critical Care Medicine (SCCM), and the Society of Hospital Medicine (SHM). The organizations were concerned that the measure “encourages the overuse of broad-spectrum antibiotics,” according to a letter the AHA sent to then Acting Administrator of CMS Andrew Slavitt.

“By encouraging the use of broad spectrum antibiotics when more targeted ones will suffice, this measure promotes the overuse of the antibiotics that are our last line of defense against drug-resistant bacteria,” the AHA’s letter states.

In its recent coverage of the healthcare organizations’ pushback to CMS’ final rule, Healthcare Finance News explained, “The SEP-1 measure requires clinicians to provide a bundle of care to all patients with possible sepsis within three hours of recognition. … But the SEP-1 measure doesn’t take into account that many serious conditions present in a similar fashion to sepsis … 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.”

CMS’ latest rule follows the same evolutionary path as previous federal guidelines. In August 2007, CMS announced that Medicare would no longer pay for additional costs associated with preventable errors, including situations known as Never Events. These are “adverse events that are serious, largely preventable, and of concern to both the public and healthcare providers for the purpose of public accountability,” according to the Leapfrog Group.

In 2014, the CDC suggested that all US hospitals have an antibiotic stewardship program (ASP) to measure and improve how antibiotics are prescribed by clinicians and utilized by patients.

Research Does Not Show Federal Sepsis Programs Work

In a paper published in the Journal of the American Medical Association (JAMA) titled, “The Importance of Shifting Sepsis Quality Measures from Processes to Outcomes,” Chanu Rhee, MD, Infectious Disease/Critical Care Physician and Associate Hospital Epidemiologist at Brigham and Women’s Hospital and Associate Professor of Population Medicine at Harvard Medical School, stressed his concerns about the new regulations.

He points to analysis which showed that though use of broad-spectrum antibiotics increased after the original 2015 SEP-1 regulations were introduced, there has been little change to patient outcomes.  

“Unfortunately, we do not have good evidence that implementation of the sepsis policy has led to an improvement in sepsis mortality rates,” Rhee told Fierce Healthcare.

Rhee believes that the latest regulations are a step in the right direction, but that more needs to be done for sepsis care. “Retiring past measures and refining future ones will help stimulate new innovations in diagnosis and treatment and ultimately improve outcomes for the many patients affected by sepsis,” he told Healthcare Finance.

Sepsis is very difficult to diagnose quickly and accurately. Delaying treatment could result in serious consequences. But clinical laboratory blood tests for blood infections can take up to three days to produce a result. During that time, a patient could be receiving the wrong antibiotic for the infection, which could lead to worse problems.

The new federal regulation is designed to ensure that patients receive the best care possible when dealing with sepsis and to lower mortality rates in those patients. It remains to be seen if it will have the desired effect.  

Jillia Schlingman

Related Information:

Feds Hope to Cut Sepsis Deaths by Hitching Medicare Payments to Treatment Stats

Healthcare Associations Push Back on CMS’ Sepsis Rule, Advocate Tweaks

Value-Based Purchasing (VBP) and SEP-1: What You Should Know

NIGMS: Sepsis Fact Sheet

CDC: What is Sepsis?

CDC: Core Elements of Antibiotic Stewardship

The Importance of Shifting Sepsis Quality Measures from Processes to Outcomes

Association Between Implementation of the Severe Sepsis and Septic Shock Early Management Bundle Performance Measure and Outcomes in Patients with Suspected Sepsis in US Hospitals

Infectious Diseases Society of America Position Paper: Recommended Revisions to the National Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) Sepsis Quality Measure

CMS to Improve Quality of Care during Hospital Inpatient Stays – 2014

UK Study Claims AI Reading of CT Scans Almost Twice as Accurate at Grading Some Cancers as Clinical Laboratory Testing of Sarcoma Biopsies

Radiological method using AI algorithms to detect, locate, and identify cancer could negate the need for invasive, painful clinical laboratory testing of tissue biopsies

Clinical laboratory testing of cancer biopsies has been the standard in oncology diagnosis for decades. But a recent study by the Institute of Cancer Research (ICR) and the Royal Marsden NHS Foundation Trust in the UK has found that, for some types of sarcomas (malignant tumors), artificial intelligence (AI) can grade the aggressiveness of tumors nearly twice as accurately as lab tests, according to an ICR news release.

This will be of interest to histopathologists and radiologist technologists who are working to develop AI deep learning algorithms to read computed tomography scans (CT scans) to speed diagnosis and treatment of cancer patients.

“Researchers used the CT scans of 170 patients treated at The Royal Marsden with the two most common forms of retroperitoneal sarcoma (RPS)—leiomyosarcoma and liposarcoma—to create an AI algorithm, which was then tested on nearly 90 patients from centers across Europe and the US,” the news release notes.

The researchers then “used a technique called radiomics to analyze the CT scan data, which can extract information about the patient’s disease from medical images, including data which can’t be distinguished by the human eye,” the new release states.

The scientists published their findings in The Lancet Oncology titled, “A CT-based Radiomics Classification Model for the Prediction of Histological Type and Tumor Grade in Retroperitoneal Sarcoma (RADSARC-R): A Retrospective Multicohort Analysis.”

The research team sought to make improvements with this type of cancer because these tumors have “a poor prognosis, upfront characterization of the tumor is difficult, and under-grading is common,” they wrote. The fact that AI reading of CT scans is a non-invasive procedure is major benefit, they added.

Christina Messiou, MD

“This is the largest and most robust study to date that has successfully developed and tested an AI model aimed at improving the diagnosis and grading of retroperitoneal sarcoma using data from CT scans,” said the study’s lead oncology radiologist Christina Messiou, MD, (above), Consultant Radiologist at The Royal Marsden NHS Foundation Trust and Professor in Imaging for Personalized Oncology at The Institute of Cancer Research, London, in a news release. Invasive medical laboratory testing of cancer biopsies may eventually become a thing of the past if this research becomes clinically available for oncology diagnosis. (Photo copyright: The Royal Marsden.)

Study Details

RPS is a relatively difficult cancer to spot, let alone diagnose. It is a rare form of soft-tissue cancer “with approximately 8,600 new cases diagnosed annually in the United States—less than 1% of all newly diagnosed malignancies,” according to Brigham and Women’s Hospital.

In their published study, the UK researchers noted that, “Although more than 50 soft tissue sarcoma radiomics studies have been completed, few include retroperitoneal sarcomas, and the majority use single-center datasets without independent validation. The limited interpretation of the quantitative radiological phenotype in retroperitoneal sarcomas and its association with tumor biology is a missed opportunity.”

According to the ICR news release, “The [AI] model accurately graded the risk—or how aggressive a tumor is likely to be—[in] 82% of the tumors analyzed, while only 44% were correctly graded using a biopsy.”

Additionally, “The [AI] model also accurately predicted the disease type [in] 84% of the sarcomas tested—meaning it can effectively differentiate between leiomyosarcoma and liposarcoma—compared with radiologists who were not able to diagnose 35% of the cases,” the news release states.

“There is an urgent need to improve the diagnosis and treatment of patients with retroperitoneal sarcoma, who currently have poor outcomes,” said the study’s first author Amani Arthur, PhD, Clinical Research Fellow at The Institute of Cancer Research, London, and Registrar at The Royal Marsden NHS Foundation Trust, in the ICR news release.

“The disease is very rare—clinicians may only see one or two cases in their career—which means diagnosis can be slow. This type of sarcoma is also difficult to treat as it can grow to large sizes and, due to the tumor’s location in the abdomen, involve complex surgery,” she continued. “Through this early research, we’ve developed an innovative AI tool using imaging data that could help us more accurately and quickly identify the type and grade of retroperitoneal sarcomas than current methods. This could improve patient outcomes by helping to speed up diagnosis of the disease, and better tailor treatment by reliably identifying the risk of each patient’s disease.

“In the next phase of the study, we will test this model in clinic on patients with potential retroperitoneal sarcomas to see if it can accurately characterize their disease and measure the performance of the technology over time,” Arthur added.

Importance of Study Findings

Speed of detection is key to successful cancer diagnoses, noted Richard Davidson, Chief Executive of Sarcoma UK, a bone and soft tissue cancer charity.

“People are more likely to survive sarcoma if their cancer is diagnosed early—when treatments can be effective and before the sarcoma has spread to other parts of the body. One in six people with sarcoma cancer wait more than a year to receive an accurate diagnosis, so any research that helps patients receive better treatment, care, information and support is welcome,” he told The Guardian.

According to the World Health Organization, cancer kills about 10 million people worldwide every year. Acquisition and medical laboratory testing of tissue biopsies is both painful to patients and time consuming. Thus, a non-invasive method of diagnosing deadly cancers quickly, accurately, and early would be a boon to oncology practices worldwide and could save thousands of lives each year.

—Kristin Althea O’Connor

Related Information:

AI Twice as Accurate as a Biopsy at Grading Aggressiveness of Some Sarcomas

AI Better than Biopsy at Assessing Some Cancers, Study Finds

AI Better than Biopsies for Grading Rare Cancer, New Research Suggests

A CT-based Radiomics Classification Model for the Prediction of Histological Type and Tumor Grade in Retroperitoneal Sarcoma (RADSARC-R): A Retrospective Multicohort Analysis

University of Gothenburg Study Findings Affirm Accuracy of Clinical Laboratory Blood Test to Diagnose Alzheimer’s Disease

Already-existing clinical laboratory blood test may be new standard for detecting Alzheimer’s biomarkers

In Sweden, an independent study of an existing blood test for Alzheimer’s disease—called ALZpath—determined that this diagnostic assay appears to be “just as good as, if not surpass, lumbar punctures and expensive brain scans at detecting signs of Alzheimer’s in the brain,” according to a report published by The Guardian.

Alzheimer’s disease is one of the worst forms of dementia and it affects more than six million people annually according to the Alzheimer’s Association. Clinical laboratory testing to diagnose the illness traditionally involves painful, invasive spinal taps and brain scans. For that reason, researchers from the University of Gothenburg in Sweden wanted to evaluate the performance of the ALZpath test when compared to these other diagnostic procedures.

Motivated to seek a less costly, less painful, Alzheimer’s biomarker for clinical laboratory testing, neuroscientist Nicholas Ashton, PhD, Assistant Professor of Neurochemistry at the University of Gothenburg, led a team of scientists that looked at other common biomarkers used to identify changes in the brain of Alzheimer’s patients. That led them to tau protein-based blood tests and specifically to the ALZpath blood test for Alzheimer’s disease developed by ALZpath, Inc., of Carlsbad, Calif.

The researchers published their findings in the journal JAMA Neurology titled, “Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology.”

In their JAMA article, they wrote, “the pTau217 immunoassay showed similar accuracies to cerebrospinal fluid biomarkers in identifying abnormal amyloid β (Aβ) and tau pathologies.”

In an earlier article published in medRxiv, Ashton et al wrote, “Phosphorylated tau (pTau) is a specific blood biomarker for Alzheimer’s disease (AD) pathology, with pTau217 considered to have the most utility. However, availability of pTau217 tests for research and clinical use has been limited.”

Thus, the discovery of an existing pTau217 assay (ALZpath) that is accessible and affordable is a boon to Alzheimer’s patients and to the doctors who treat them.

“The ALZpath pTau217 assay showed high diagnostic accuracy in identifying elevated amyloid (AUC, 0.92-0.96; 95%CI 0.89-0.99) and tau (AUC, 0.93-0.97; 95%CI 0.84-0.99) in the brain across all cohorts. These accuracies were significantly higher than other plasma biomarker combinations and equivalent to CSF [cerebrospinal fluid] biomarkers,” an ALZpath press release noted.

“This is an instrumental finding in blood-based biomarkers for Alzheimer’s, paving the way for the clinical use of the ALZpath pTau217 assay,” stated Henrik Zetterberg, MD, PhD (above), Professor of Neurochemistry at the University of Gothenburg and co-author of the study. “This robust assay is already used in multiple labs around the globe.” Clinical laboratories may soon be receiving doctors’ orders for pTau217 blood tests for Alzheimer’s patients. (Photo copyright: University of Gothenburg.)

Study Details

Ashton’s team conducted a cohort study that “examined data from three single-center observational cohorts.” The cohorts included:

“Participants included individuals with and without cognitive impairment grouped by amyloid and tau (AT) status using PET or CSF biomarkers. Data were analyzed from February to June 2023,” the researchers wrote. 

These trials from the US, Canada, and Spain featured 786 participants and featured “either a lumbar puncture or an amyloid PET scan to identify signs of amyloid and tau proteins—hallmarks of Alzheimer’s disease,” The Guardian reported, adding that results of the University of Gothenburg’s study showed that the ALZpath pTau217 blood test “was superior to brain atrophy assessments, in identifying signs of Alzheimer’s.”

“80% of individuals could be definitively diagnosed on a blood test without any other investigation,” Ashton told The Guardian.

Diagnosis Needed to Receive Alzheimer’s Disease Treatments

“If you’re going to receive [the new drugs], you need to prove that you have amyloid in the brain,” Ashton told The Guardian. “It’s just impossible to do spinal taps and brain scans on everyone that would need it worldwide. So, this is where the blood test [has] a huge potential.”

Even countries where such drugs were not yet available (like the UK) would benefit, Ashton said, because the test, “Could potentially say that this is not Alzheimer’s disease and it could be another type of dementia, which would help to direct the patient’s management and treatment routine.”

However, Ashton himself noted the limitations of the new findings—specifically that there is no success shown yet in Alzheimer’s drugs being taken by symptom-free individuals.

“If you do have amyloid in the brain at 50 years of age, the blood test will be positive,” he said. “But what we recommend, and what the guidelines recommend with these blood tests, is that these are to help clinicians—so someone must have had some objective concern that they have Alzheimer’s disease, or [that] their memory is declining,” he told The Guardian.

Experts on the Study Findings

“Blood tests could be used to screen everyone over 50-years old every few years, in much the same way as they are now screened for high cholesterol,” David Curtis, MD, PhD, Honorary Professor in the Genetics, Evolution and Environment department at University College London, told The Guardian.

“Results from these tests could be clear enough to not require further follow-up investigations for some people living with Alzheimer’s disease, which could speed up the diagnosis pathway significantly in future,” Richard Oakley, PhD, Associate Director of Research and Innovation at the Alzheimer’s Society, UK, told The Guardian.

Though Oakley found the findings promising, he pointed out what should come next. “We still need to see more research across different communities to understand how effective these blood tests are across everyone who lives with Alzheimer’s disease,” he said.

“Expanding access to this highly accurate Alzheimer’s disease biomarker is crucial for wider evaluation and implementation of AD blood tests,” the researchers wrote in JAMA Neurology.

“ALZpath makers are in discussions with labs in the UK to launch it for clinical use this year, and one of the co-authors, Henrik Zetterberg, MD, PhD, Professor of Neurochemistry at the University of Gothenburg, is making the assay available for research use as part of the ‘biomarker factory’ at UCL,” The Guardian reported.

In the US, to be prescribed any of the available Alzheimer’s medications, a doctor must diagnose that the patient has amyloid in the brain. A pTau217 diagnostic blood test could be used to make such a diagnosis. Currently, however, the test is only available “for research studies through select partner labs,” Time reported.

“But later this month, doctors in the US will be able to order the test for use with patients. (Some laboratory-developed tests performed by certain certified labs don’t require clearance from the US Food and Drug Administration.),” Time added.

It may be that the University of Gothenburg study will encourage Alzheimer’s doctors in the UK and around the world to consider ordering pTau217 diagnostic blood tests from clinical laboratories, rather than prescribing spinal taps and brains scans for their Alzheimer’s patients.

—Kristin Althea O’Connor

Related Information:

New Study Published in JAMA Neurology Affirms High Diagnostic Accuracy of ALZpath’s pTau217 Test in Identifying Amyloid and Tau in the Brain

Blood Test Could Revolutionize Diagnosis of Alzheimer’s, Experts Say

Simple Blood Tests for Dementia to Be Trialed in NHS

A Blood Test for Alzheimer’s Disease Is Almost Here

Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology

Alzheimer’s Disease Facts and Figures

Scientists Develop Blood Test for Alzheimer’s Disease

UCLA Researchers Discover Organisms in Semen Microbiome That Affect Sperm Motility and Male Fertility

Study findings could lead to new clinical laboratory testing biomarkers designed to assess for male infertility

Clinical laboratories are increasingly performing tests that have as their biomarkers the DNA and enzymes found in human microbiota. And microbiologists and epidemiologists know that like other environments within the human body, semen has its own microbiome. Now, a study conducted at the University of California, Los Angeles (UCLA) has found that the health of semen microbiome may be linked to male infertility. 

The UCLA researchers discovered a small group of microorganisms within semen that may impair the sperm’s motility (its ability to swim) and affect fertility.

A total of 73 individuals were included in the study. About half of the subjects were fertile and already had children, while the remaining men were under consultation for fertility issues.

“These are people who have been trying to get pregnant with their partner, and they’ve been unsuccessful,” Sriram Eleswarapu, MD, PhD, a urologist at UCLA and co-author of the study, told Scientific American. “This latter group’s semen samples had a lower sperm count or motility, both of which can contribute to infertility.”

The researchers published their findings in Scientific Reports titled, “Semen Microbiota Are Dramatically Altered in Men with Abnormal Sperm Parameters.”

“There is much more to explore regarding the microbiome and its connection to male infertility,” said Vadim Osadchiy, MD (above), a resident in the Department of Urology at UCLA and lead author of the study, in a UCLA news release. “However, these findings provide valuable insights that can lead us in the right direction for a deeper understanding of this correlation.” Might it also lead to new biomarkers for clinical laboratory testing for male infertility? (Photo copyright: UCLA.)

Genetic Sequencing Used to Identify Bacteria in Semen Microbiome

Most of the microbes present in the semen microbiome originate in the glands of the male upper reproductive tract, including the testes, seminal vesicles and prostate, and contribute various components to semen. “Drifter” bacteria that comes from urine and the urethra can also accumulate in the fluid during ejaculation. Microbes from an individual’s blood, or his partner’s, may also aggregate in semen. It is unknown how these bacteria might affect health.

“I would assume that there are bacteria that are net beneficial, that maybe secrete certain kinds of cytokines or chemicals that improve the fertility milieu for a person, and then there are likely many that have negative side effects,” Eleswarapu told Scientific American.

The scientists used genetic sequencing to identify different bacteria species present within the semen microbiome. They found five species that were common among all the study participants. But men with more of the microbe Lactobacillus iners (L. iners) were likelier to have impaired sperm motility and experience fertility issues.

This discovery was of special interest to the team because L. iners is commonly found in the vaginal microbiome. In females, high levels of L. iners are associated with bacterial vaginosis and have been linked to infertility in women. This is the first study that found a negative association between L. iners and male fertility. 

The researchers plan to investigate specific molecules and proteins contained in the bacteria to find out whether they slow down sperm in a clinical laboratory situation.

“If we can identify how they exert that influence, then we have some drug targets,” Eleswarapu noted.

Targeting Bacteria That Cause Infertility

The team also discovered that three types of bacteria found in the Pseudomonas genus were present in patients who had both normal and abnormal sperm concentrations. Patients with abnormal sperm concentrations had more Pseudomonas fluorescens and Pseudomonas stutzeri and less Pseudomonas putida in their samples.

According to the federal National Institute of Child Health and Human Development (NICHD), “one-third of infertility cases are caused by male reproductive issues, one-third by female reproductive issues, and the remaining one-third by both male and female reproductive issues or unknown factors.” Thus, learning more about how the semen microbiome may be involved in infertility could aid in the development of drugs that target specific bacteria.

“Our research aligns with evidence from smaller studies and will pave the way for future, more comprehensive investigations to unravel the complex relationship between the semen microbiome and fertility,” said urologist Vadim Osadchiy, MD, a resident in the Department of Urology at UCLA and lead author of the study, in a UCLA news release

More research is needed. For example, it’s unclear if there are any links between the health of semen microbiome and other microbiomes that exist in the body, such as the gut microbiome, that cause infertility. Nevertheless, this research could lead to new biomarkers for clinical laboratory testing to help couples who are experiencing fertility issues. 

—JP Schlingman

Related Information:

Semen Microbiome Health May Impact Male Fertility

Semen Microbiota Are Dramatically Altered in Men with Abnormal Sperm Parameters

Semen Has Its Own Microbiome—and It Might Influence Fertility

How Common is Male Infertility, and What Are Its Causes?

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