Findings may lead to new clinical laboratory testing and treatments for Parkinson’s patients
Gut bacteria have repeatedly been proven to perform critical roles in the development of certain diseases. And many clinical laboratory tests use human microbiota as biomarkers.
Now, researchers at Nagoya University Graduate School of Medicine in Japan have discovered a link between microbes in the gut and the brain. The connection may play a part in the development of Parkinson’s disease, according to a Nagoya University news release.
The researchers found that a reduction in the genes responsible for synthesizing riboflavin (vitamin B2) and biotin (vitamin B7) may increase the likelihood of developing Parkinson’s.
They also determined that the lack of these genes may lessen the integrity of the intestinal barrier that prevents toxins from entering the bloodstream causing the inflammation often seen in Parkinson’s patients.
“Supplementation therapy targeting riboflavin and biotin holds promise as a potential therapeutic avenue for alleviating Parkinson’s symptoms and slowing disease progression,” said lead researcher Hiroshi Nishiwaki, PhD, Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, in a news release. (Photo copyright: Nagoya University.)
Key Deficiencies in Parkinson’s Patients
According to the Parkinson’s Foundation, nearly one million people in the US are living with Parkinson’s and that number is expected to increase to 1.2 million by the year 2030. Approximately 90,000 new cases of Parkinson’s are diagnosed in the US each year, and more than 10 million people are living with the disease worldwide.
To perform their research, the Nagoya University team analyzed stool samples from 94 Parkinson’s patients from Japan, the US, Germany, China, and Taiwan. They also included 73 relatively healthy controls from Japan. They then used shotgun sequencing (a laboratory technique for determining the DNA sequence of an organism’s genome) to gain a better understanding of the microbial community and genetic makeup of each sample.
The scientists discovered a decrease in B2 and B7 vitamins in patients diagnosed with Parkinson’s. B vitamins promote the production and functions of short-chain fatty acids (SCFA) and polyamines.
“Supplementation of riboflavin and/or biotin is likely to be beneficial in a subset of Parkinson’s disease patients, in which gut dysbiosis plays pivotal roles,” the authors wrote in NPJ-Parkinson’s Disease.
The examination of fecal metabolites in Parkinson’s patients revealed a reduction in both components.
“Deficiencies in polyamines and SCFAs could lead to thinning of the intestinal mucus layer, increasing intestinal permeability, both of which have been observed in Parkinson’s,” said Hiroshi Nishiwaki, PhD, a professor at Nagoya University Graduate School of Medicine and a lead researcher for the study, in the news release.
“This higher permeability exposes nerves to toxins, contributing to abnormal aggregation of alpha-synuclein, activating the immune cells in the brain, and leading to long-term inflammation,” he added.
The team surmises that the weakened protective layer in the gut exposes the intestinal nervous system to more of the toxins people experience in everyday life, such as chemicals, pesticides, and herbicides. These types of toxins lead to the overproduction of alpha-synuclein fibrils. These molecules are aggregates of the α-synuclein protein that form into long, thread-like structures which are primarily found in the brains of individuals with neurodegenerative diseases like Parkinson’s.
Alpha-synuclein fibrils amass in dopamine-producing cells in the brain and increase the type of inflammation that leads to the debilitating motor skills and dementia symptoms of Parkinson’s.
Precision Medicine Analysis Suggested
Due to their research, the team proposes that high doses of vitamin B may help reduce the damage of toxins on the gut microbiome, help protect against neurodegenerative diseases like Parkinson’s, and aid in the creation of personalized therapy plans for patients.
“We could perform gut microbiota analysis on patients or conduct fecal metabolite analysis,” Nishiwaki noted. “Using these findings, we could identify individuals with specific deficiencies and administer oral riboflavin and biotin supplements to those with decreased levels, potentially creating an effective treatment.”
The results of the Nagoya University study illustrate the importance of a healthy gut microbiome in the prevention of disease. Altering the bacterial level in the gut may enable doctors to stave off the progression of neurodegenerative illnesses like Parkinson’s disease.
Discovery could lead to new clinical laboratory testing for cancer screening in new mothers
Any clinical laboratory test that returns unexpected results is worth looking into more deeply. Such was the case with a recent study conducted by the National Institutes of Health (NIH), which investigated cases of pregnant women who received “unusual” results to prenatal lab tests conducted at a dozen labs in North America.
Following cancer screening protocols that included rapid whole-body magnetic resonance imaging, NIH scientists discovered “previously undetected cancers in 48.6% of pregnant people who had abnormal results for prenatal cell-free DNA (cfDNA) testing used to screen for chromosomal disorders in the fetus,” according to an NIH news release.
“They looked like healthy young women, and they reported themselves as being healthy,” Diana Bianchi, MD, head of the Prenatal Genomics and Therapy Section for the Medical Genetics Branch at the NIH’s National Human Genetics Research Institute, and senior author of the government study, told the Associated Press (AP).
While cfDNA tests are not diagnostic, pathologists and clinical laboratory managers involved in genetic testing are likely familiar with them. The blood tests are used by expectant mothers to assess risk of a fetus with an abnormal number of chromosomes that could suggest disorders such as Down Syndrome, according to ARUP Laboratories.
Unexpected results from tests draw attention. This one seems to have a chance to get more traction with labs because the results point to a prenatal test having some success predicting cancer, even if incidentally.
“[The study participants] and their care providers need to take the results seriously and have additional testing because in that population there is a 48% risk of cancer,” Diana Bianchi, MD, senior author of the NIH study, told the AP. (Photo copyright: National Institutes of Health.)
Cancer Found in about Half of Those with Abnormal cfDNA
The NIH researchers started a long-term study, called IDENTIFY, to learn more about abnormal cfDNA results that could suggest cancer. Study participants must be:
Pregnant or postpartum with no known cancer.
Recipients of “unusual clinical cfDNA-sequencing results or results that are non-reportable (fetal aneuploidy status could not be assessed) from one of 12 different commercial laboratories,” they wrote in NEJM.
For the study’s initial cohort of 107 participants, researchers repeated cfDNA sequencing testing and coordinated standard medical diagnostic tests (such as Pap smears) and whole-body magnetic resonance imaging.
52 women (48.6%) were found to have “hidden cancers.”
32 had blood cancers.
20 had solid tumors in the breast, bile duct, colon, pancreas, lung, kidney, bone, and adrenal gland.
13 of the 20 with solid tumors were able to access “potentially curative treatments.”
55 women did not have cancer and may have obtained an unreliable cfDNA result.
“In this study, 48.6% of participants who received unusual or nonreportable clinical cfDNA-sequencing results had an occult cancer (cancer of unknown primary).
“Further study of DNA-sequencing patterns that are suggestive of occult cancer during prenatal screening is warranted,” the researchers wrote in NEJM.
Follow-Up Testing Needed
Cancers found in the study participants “included colorectal, breast, lung and pancreatic cancers, as well as lymphoma, cholangiocarcinoma and renal carcinoma. The screening test analyzes placental DNA fragments circulating in the maternal bloodstream to identify an extra chromosome or to determine the baby’s sex,” according to the NIH news release.
Bianchi told AP the study results also pointed to a “very chaotic” pattern in DNA-sequencing of women with cancer, and that more research is needed to find out who should be screened for cancer.
Clinical laboratories and pathologists who analyze cfDNA tests could take a leadership role in assessing current standards for the tests, determining how suspicious results are reported, and suggesting needed changes.
Researchers tracked “excess deaths” among adults aged 25 to 44 years and found disparate causes to blame
Studies conducted at the University of Minnesota and Boston University found that mortality rates among young adults have risen substantially since 2010 due to a variety of factors, pointing to a possible “mortality crisis” as they get older.
The researchers used data from the Centers for Disease Control and Prevention (CDC) and US Census Bureau to analyze nearly 3.4 million deaths in the US between 1999 and 2023 among adults aged 25 to 44 years, according to a Boston University press release.
They then used mortality data from 1999 through 2010 to project expected death rates for the later years and compared those projections to the actual post-2010 mortality rate to calculate the number of “excess deaths,” defined as “those [deaths] above what had been projected for a given period.”
“What we didn’t expect is how many different causes of death have really grown for these early adults,” said study lead author Elizabeth Wrigley-Field, PhD, of the University of Minnesota, in a U of M pressrelease. “It’s drug and alcohol deaths, but it’s also car collisions, it’s circulatory and metabolic diseases—causes that are very different from each other. That tells us this isn’t one simple problem to fix, but something broader.”
From that perspective, clinical laboratories could be part of the solution in tracking down these early conditions and steering young patients towards healthier outcomes.
“The rise in opiate deaths has been devastating for Americans in early and middle adulthood,” said sociologist Elizabeth Wrigley-Field, PhD, of the University of Minnesota in a press release. (Photo copyright: University of Minnesota.)
One-Two Punch
In 2019, excess mortality amounted to 41.7 deaths per 100,000 population, nearly 35% higher than expected, the researchers wrote. Then, in 2021 during the pandemic, excess mortality from all causes was nearly three times higher: 116.2 deaths per 100,000 population. In 2023, excess mortality decreased, but only to 79.1 deaths per 100,000 population.
“As a result, early adult mortality was 70.0% higher in 2023 than it would have been had pre-2011 trends continued,” the researchers wrote in Jama Network Open.
Speaking with Healio, Wrigley-Field described a “one-two punch that these age groups have seen: first, rising mortality since 2010; then the pandemic, only partially recovered from.”
Five causes accounted for nearly 75% of the excess deaths in 2023, the researchers found:
Drug poisoning, such as opiate overdoses (31.8%)
Residual natural causes (16%)
Transport-related deaths, such as motor vehicle accidents (14.1%)
Alcohol-related deaths (8.5%)
Homicide (8.2%)
The researchers also found that cardiometabolic conditions accounted for 9.2% of excess deaths. These include metabolic, circulatory and endocrine, and nutritional conditions, they noted.
Study co-author Andrew Stokes, PhD, of Boston University characterized the latter as a red flag, according to the Boston University press release. “Usually, it takes a lifetime to manifest cardiovascular disease and related mortality,” he said.
“Our findings underscore the urgent need for comprehensive policies to address the structural factors driving worsening health among recent generations of young adults,” he said in the U of M press release. “Solutions may include expanding access to nutritious foods, strengthening social services, and increasing regulation of industries that affect public health.”
Policy Measures
In their paper, the researchers suggested that policymakers should pay more attention to underlying causes such as opioid use, alcohol consumption, and traffic safety, as well as “ongoing consequences of the COVID-19 pandemic—which may be expressed in causes of death related to long-term consequences of infection, medical disruption, and social dislocation—and to deleterious health trends that predated it.”
“Individuals might not necessarily be able to reverse those factors, or their consequences, on their own, but public health collectively has been very successful at improving health through policies like tobacco regulation, to name one example,” Wrigley-Field told Healio.
She added that “the cardiometabolic causes of death stand out because these are really a bellwether of population health. These causes tend to be very responsive to the fundamentals of healthy living: healthy food, exercise, sleep, limited exposure to tobacco and air pollution, and limited experience of excessive stress.”
Young adults have also been dealing with the “expansion of industries that affect public health—processed foods and beverages, prescription drugs and OxyContin, alcohol, combined with this creeping effect of the obesity epidemic,” Stokes said.
He added: “These are the ages, 25 to 44, in which behaviors become entrenched and life course risks start to develop. And if we’re seeing this excess mortality in this generation now, it’s also an indication of what may happen to population health as a whole in decades ahead as this generation ages.”
This information can inform physicians and laboratorians about what diagnostic tests to consider for young people showing symptoms, even if their ages traditionally don’t indicate a chronic condition.
Hospitals in 38 states confirmed patient infections of the dangerous, drug-resistant fungus
Rapidly spreading Candida auris fungus is once again showing up in hospitals throughout the United States, with multiple cases confirmed in Georgia and Florida. Hospital laboratories and pathology departments are encouraged to take advantage of CDC resources to help in the diagnosis of this deadly pathogen.
Candida auris (C. auris) spreads between patients in hospital settings, is resistant to anti-fungal medications, and can cause severe illness, according to the Centers for Disease Control and Prevention (CDC). Tracking data from CDC’s National Notifiable Diseases Surveillance System found 4,514 new clinical cases of C. auris in the US in 2023.
“The number of clinical cases has continued to increase since the first US case was reported in 2016,” said the CDC of past outbreaks of C. auris. “Based on information from a limited number of patients, 30–60% of people with C. auris infections have died. However, many of these people had other serious illnesses that also increased their risk of death.” The fungus has been spreading at a high rate from 2016-2023 with several cases cropping up recently in Georgia.
According to representatives from the Georgia Department of Public Health, “the state has seen over 1,300 cases as of the end of February,” WJCL reported.
The Hill reports a significant recent increase in the spread of the fungus in all but 12 states. Though the number of cases in each state remains small, the overall percentage of increased cases is large and growing.
And a study conducted at Jackson Health System in Miami, Fla., and published in the American Journal of Infection Control, found that “The volumes of clinical cultures with C. auris have rapidly increased, accompanied by an expansion in the sources of infection.”
“If you get infected with this pathogen that’s resistant to any treatment, there’s no treatment we can give you to help combat it. You’re all on your own,” Melissa Nolan, PhD, associate professor of epidemiology and biostatistics at the Arnold School of Public Health, University of South Carolina, told Nexstar. (Photo copyright: University of South Carolina.)
CDC Recommendations
The deadly fungus was first detected in 2016 in US hospitals, and the number of cases in hospital patients has grown every year based on CDC data from 2023. Invasive medical procedures can provide a gateway for C. auris to infect patients, and the immunosuppressed nature of these patients can lead to further complications.
Invasive procedures that could expose a patient to C. auris include the placing of breathing and feeding tubes, and the insertion of vein or urinary catheters.
“We’ve had four people at one time on and off over the past few months, and in years past, it was unusual to have one or even two people with Candida auris in our hospital,” Timothy Connelly, MD, told WJCL about the spread of the fungus at Memorial Health in Savannah, Ga.
Cases have also rapidly increased in Miami according to the Jackson Health System study. The researchers found that, “The volumes of clinical cultures increased every year and infection sources expanded.”
The CDC considers C. auris “an urgent antimicrobial resistance threat” based on the severe risk an infected patient can face. “The rapid rise and geographic spread of cases is concerning and emphasizes the need for continued surveillance, expanded lab capacity, quicker diagnostic tests, and adherence to proven infection prevention and control,” said Meghan Lyman, MD, in a CDC news release.
Fungal Infection is Difficult to Treat and Diagnose
C. auris has been shown to be resistant to antifungal medications, making it an acute threat to ill patients. And since it tends to infect already sick patients, it can be difficult to detect because symptoms of infection can be generic, such as fever or chills.
The fungus is also adept at surviving on hospital surfaces.
“It’s really good at just being, generally speaking, in the environment,” Melissa Nolan, PhD, associate professor of epidemiology and biostatistics at the Arnold School of Public Health, University of South Carolina, told Nexstar. “So, if you have it on a patient’s bed for example, on the railing, and you go to wipe everything down, if in whatever way maybe a couple of pathogens didn’t get cleared, then they’re becoming resistant. And so over time, they can kind of grow and populate in that hospital environment.”
CDC Resources to Help Identify C. auris
C. auris also can be misidentified with other candida species fungi. The CDC recommends identification using a diagnostic device “based on matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF).” The CDC also recommends using supplemental MALDI-TOF databases and molecular methods to help distinguish C. auris from other candida.
Prompt clinical laboratory diagnosis is extremely important to stem outbreaks as they become more frequent in hospital settings. The CDC offers resources for hospital pathology departments to aid in screening and detection.
“I think we need to do a better job of predicting,” Nolan told Nexstar. “Moving forward [we need] more funding to support quality surveillance of these potential infectious strains so that we can know in advance, and we can do a better job of stopping disease spread before it becomes a problem.”
According to the CDC, the fungus typically spreads in hospital settings and is not known to affect healthy people.
Artificial intelligence tools for radiology, clinical laboratory, and pathology diagnostics continue to advance and improve
Researchers in Germany have developed a fully automated, artificial intelligence (AI) tool that improves the diagnosis of prostate cancer. Developed by mediaire, a company that creates AI-based tools for radiologists, the software reduces clinical workloads and could be beneficial in counteracting issues associated with variability in magnetic resonance imaging (MRI) reporting. This is another example of AI’s growth in the clinical diagnostic industry, including clinical laboratory and pathology medicine.
The software, called mdprostate, has received the mandatory certification mark (CE or European Conformity) for products sold within the European Economic Area (EEA). It is now commercially available in those countries and was recently incorporated into the picture archiving and communications system (PACS) of some healthcare organizations and applied to a group of patients who had undergone a multiparametric prostate MRI (mpMRI).
The goal was to compare the overall performance of mdprostate against radiologists who executed the initial interpretations of the mpMRIs, according to Health Imaging.
“Mdprostate is intended to support radiologists by automating time-consuming processes and improving the objectivity of diagnosis through data quantification,” said Tonia Michaely, chief of staff at mediaire, in a news release.
“By providing objective assessments and standardizing lesion detection and classification, AI has the potential to augment radiologists’ performance throughout the PCa [prostate cancer] diagnostic pathway,” Nadine Bayerl, Dr. med., a radiologist with the Institute of Radiology at University Hospital Erlangen and corresponding author of the mediaire study, told Health Imaging. (Photo copyright: University Hospital Erlangen.)
Scoring Cancer Risk
To perform the comparison, a team of researchers applied the AI tool to 123 prostate MRI exams followed by systematic and targeted biopsies. The software was instructed to automatically segment the prostrate, calculate prostate volume, and classify lesions per the Prostate Imaging Reporting and Data System (PI-RADS).
PI-RADS, according to the America College of Radiology, is a reporting method that indicates how likely a lesion is to be clinically significant cancer on a score of one to five:
PI-RADS 1: very low (clinically significant cancer is highly unlikely to be present).
PI-RADS 2: low (clinically significant cancer is unlikely to be present).
PI-RADS 3: intermediate (the presence of clinically significant cancer is equivocal).
PI-RADS 4: high (clinically significant cancer is likely to be present).
PI-RADS 5: very high (clinically significant cancer is highly likely to be present).
For PI-RADS scores greater than two, mdprostate generated 100% sensitivity and dismissed all cancers for lesions that were below that threshold. For PI-RADS scores of four or higher, the AI tool yielded 85.5% sensitivity and specificity of 63.2% for clinically significant cancers.
Deep Learning in Diagnostic Pathway
“In practical terms, these results indicate that when a case falls below the PI-RADS ≥ 2 cutoff, clinicians can rule out malignancy with a high degree of confidence,” the authors explained in the European Journal of Radiology. “This capability is particularly valuable in clinical decision-making, as it allows for the safe avoidance of unnecessary biopsies or further invasive procedures in these patients.”
“Recent advances in deep learning algorithms, facilitated by larger labeled datasets, improved computing hardware, and refined training techniques, have led to several studies highlighting the diagnostic value of deep learning algorithms in prostate imaging,” radiologist Nadine Bayerl, Dr. med., Institute of Radiology at University Hospital Erlangen and corresponding author of the study, told Health Imaging.
The software “demonstrated high diagnostic performance in identifying and grading prostate lesions, with results comparable to those reported in meta-analyses of expert readers using PI-RADS,” the researchers noted in their published study.
“Its ability to standardize evaluations and potentially reduce variability underscores its potential as a valuable adjunct in the prostate cancer diagnostic pathway. The high accuracy of mdprostate, particularly in ruling out prostate cancers, highlights its clinical utility by reducing workload and enhancing patient outcomes,” they concluded.
AI in Clinical Laboratories and Pathology
Dark Daily has frequently covered AI’s expanding role in clinical laboratory testing and pathology diagnostics. At the recent Executive War College, a dozen sessions explored its growth in the industry. During one session, Sam Terese, CEO and president at Alverno Laboratories said, “AI is allowing us to drive our business. It is really resonating that we need to use AI in the future.”
Members who could not attend the 2025 Executive War College can order audio recordings of these valuable sessions by clicking here.
