Coca-Cola has recalled its drinks in some countries across Europe because they contain “higher levels” of a chemical called chlorate.

A biomarker signature using brain activity measurements predicted pain sensitivity.The signature combined sensorimotor peak alpha frequency and corticomotor excitability.The study involved 150 people who received nerve injections to test prolonged pain.

A novel biomarker signature that assessed cortical activity predicted individual pain sensitivity, the PREDICT validation study showed.
The signature consisted of two measures: sensorimotor peak alpha frequency (PAF) and corticomotor excitability (CME). In the training set, it correctly classified study participants with high or low pain sensitivity with an area under the curve (AUC) of 1.00.
In the test set, the signature had an AUC of 0.88 (95% CI 0.78-0.99), reported David Seminowicz, PhD, of the University of Western Ontario in London, Canada, and co-authors in JAMA Neurology.
Results were reproduced across a range of parameters. The PAF and CME biomarkers showed good to excellent test-retest reliability.
“The combination of biomarker accuracy, reproducibility, reliability, and pain model validity suggests high potential for clinical translation, particularly in predicting the transition from acute to chronic pain,” Seminowicz and colleagues wrote.
PAF is the dominant sensorimotor cortical oscillation in the 8-12 Hz (alpha) range. CME is the efficacy of relaying signals from the primary motor cortex to peripheral muscles. Previous work showed that slower PAF before pain onset and reduced CME during prolonged pain were associated with more pain, while faster PAF and increased CME were associated with less pain.
“Given that individuals who experience higher pain in the early stages of a prolonged pain episode (e.g., postsurgery) are more likely to develop chronic pain in the future, slow PAF before an anticipated prolonged pain episode and/or CME depression during the acute stages of pain could be predictors for the transition to chronic pain,” the researchers noted.
Identifying objective biomarkers to track pain severity has been dubbed “the holy grail” of pain neuroscience, observed Prasad Shirvalkar, MD, PhD, of the University of California San Francisco, and Christopher Rozell, PhD, of the Georgia Institute of Technology in Atlanta, in an accompanying editorial.
“While pain is among the most fundamental, ubiquitous, and adaptive experiences that can befall an organism, there is still a murky understanding of how pain is generated in the nervous system,” they noted. The consensus on mechanisms underlying chronic pain — pain that persists for more than 3 months, which affects 21% of U.S. adults — is even less clear.
The PAF and CME signature “will likely have broad applicability across many medical fields,” Shirvalkar and Rozell said. “If successfully translated into clinical practice, biomarkers that predict a transition to chronic pain would have a tremendous impact for the treatment of millions of individuals.”
Advances in pain biomarkers also need to incorporate advances in global neuroethics guidance and address ethical concerns about pain treatment, the editorialists pointed out. “We must take care to ensure that quantitative measures do not supplant lived experience reports, introduce distrust in the physician-patient relationship, set unrealistic patient expectations, or exacerbate existing inequalities in pain treatment across this vulnerable population,” they wrote.
The PREDICT validation study included 150 people (100 in the training set, and 50 in the test set) who were given an injection of nerve growth factor into the right masseter muscle on day 0 and day 2 to induce prolonged jaw pain that lasted up to 4 weeks.
Participants were healthy adults recruited in Australia with a mean age of 25. They had no history of chronic pain or a neurological or psychiatric condition, and 84 participants (56%) were men.
The research aimed to determine whether individuals could be accurately classified as having high or low pain sensitivity based on baseline PAF and CME readings. The researchers used electroencephalography to assess PAF and transcranial magnetic stimulation with resulting evoked potentials to assess CME on day 0, day 2, and day 5.
The primary outcomes were jaw pain on chewing and yawning. Pain sensitivity was assessed twice daily from day 1 through day 30 through self-reported pain scores.
Seminowicz and colleagues used five machine learning models on the training set. Of these, the winning classifier was logistic regression. Including sex and pain catastrophizing as covariates did not improve model performance.
The study assessed healthy participants using an experimental pain model; results may not apply to other people or other circumstances, the researchers acknowledged.

Judy George covers neurology and neuroscience news for MedPage Today, writing about brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep, pain, and more. Follow

Disclosures
This project was funded by the National Institutes of Health (NIH).Seminowicz and one co-author reported having a patent issued for peak alpha frequency through the University of Maryland in Baltimore. No other disclosures were reported.Shirvalkar reported relationships with the NIH, Medtronic, QuantalX, and a patent pending for closed-loop deep brain stimulation for chronic pain. Rozell reported personal fees from Motif Neurotech and a patent pending for a system to identify transitions in brain states for depression.

Primary Source
JAMA Neurology
Source Reference: Chowdhury NS, et al “Predicting individual pain sensitivity using a novel cortical biomarker signature” JAMA Neurol 2025; DOI: 10.1001/jamaneurol.2024.4857.

Secondary Source
JAMA Neurology
Source Reference: Shirvalkar P, Rozell CJ “Brain biomarkers for pain sensitivity” JAMA Neurol 2025; DOI: 10.1001/jamaneurol.2024.4743.

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LOS ANGELES — Clinicians working in advanced heart failure vented their frustrations about the shrinking number of device therapies left from round after round of FDA recalls. Could a changed regulatory climate under the Trump administration bring about more treatment options?
The question came up during an audience Q&A session at the Society of Thoracic Surgeons (STS) annual meeting. While panelists were generally hesitant to make predictions about politics, Richard Lee, MD, JD, MBA, of Augusta University Medical Center in Georgia, laid out how things could go two ways in the years ahead.
One is a push to move device development faster along in industry, with a higher tolerance for defects. On the other hand, the reduced government support for research funding, evident already, would suggest no economic support for medical device makers.
“I personally think it’s going to be both,” said Lee. “I could be wrong.”
A renewed appetite for innovation would bring some relief to the field of advanced heart failure in particular, which is now down to just one durable left ventricular assist device (LVAD) on the market, the HeartMate III. In 2021, the competing HeartWare ventricular assist device had been pulled for pump stop events, plus excess neurological events and mortality when compared with LVADs.
A recent study identified 157 cardiovascular devices recalled from 2013 to 2022. Recalls were commonly attributed to device design (31.4%), process control (16.1%), or component design or selection (7.3%).
At STS, physicians shared how they were navigating the various FDA recalls and the medicolegal implications of using devices under these recalls.
Courtney Maxey-Jones, MD, of CNY Medical Services in Baldwinsville, New York, recounted her experiences seeing device after device taken out of commission for various reasons when she could have still used them to save patient lives. In one instance, her hospital administrators had locked up all the Cardiohelp systems that were subject to a class I recall due to stiff hand cranks impeding an emergency drive.
Those were decisions made by “people who didn’t have to look at the patients that no longer had [the device] as an option,” Maxey-Jones lamented. “In order to be able to continue to provide high-level care to, frankly, the sickest of the sick patients, I’m not choosing a new prescription med. I’m deciding if I can give you mechanical circulatory support so that you don’t die in front of me.”
“If we’re going to continue to be the best advocates for our patients, we need to continue to insist on and invest in a diverse portfolio of mechanical support devices, which we can then match to our individual patient needs,” stressed Leora Yarboro, MD, of UVA Health in Charlottesville, Virginia.
“When something’s removed and not replaced with something that is also going to do the same thing for your patients, you really hope that you’re going to have some therapies for them. It’s our job … to make sure that patients who are supported with the device continue to be followed and supported as well, even if the device itself is no longer being manufactured,” she said.
So which devices are still okay to be used in clinical practice?
“Maybe we’re going to be sued for it, but I think it’s still reasonable to provide the best effort that you can … to save people’s lives with the tools that we have available,” said Yarboro.
“All technology has limitations, and it’s our shared responsibility to identify and report findings through our registry data … In this way, we can continue to be the best advocates for our patients, and remember that the goal behind reporting is not to have these life-saving devices be removed from the market, rather to ensure that the technology continues to evolve and to allow for informed decision-making by all,” she said.
Lee, a practicing lawyer, provided some reassuring data about the legalities of using medical devices under recall. In searching the national database, and consulting with lawyers who work with personal injury law, he could only identify two cases where a physician was named for failure to incorporate an action after receiving a recall notice — both got dismissed. “Right now, this is virgin territory,” he said.
What is more legally worrying is off-label use of drugs and devices, which he said he now avoids as much as he can.
Good communication with the patient and the patient’s family is key, according to Lee.
For example, the Impella 5.5 with SmartAssist is technically under class I recall and affected products are advised to be avoided unless no other product is available. As for Impella-assisted high-risk surgery, “I love it, and this is not an endorsement … I’m not going to stop doing it,” said Lee.
“I am not. I’m going to increase doing it, but now I’m going to tell every single patient ‘I’m doing this, they’re doing education for it, and you will have a risk … You can get a clot in the thing and it goes up to your head,'” he added.
If the patients say “no,” then he will back off on the procedure, he said.

Nicole Lou is a reporter for MedPage Today, where she covers cardiology news and other developments in medicine. Follow

Disclosures
Lee is a partner at Hochman and Lee, LLC.Maxey-Jones had no disclosures.Yarboro disclosed a prior speaker/honoraria relationship with Arthrex.

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SAN FRANCISCO — Circulating tumor DNA (ctDNA) measurements showed promise for identifying patients with early colorectal cancer (CRC) most likely to benefit from adjuvant therapy, analyses of two large clinical trials suggested.
Patients who had positive ctDNA tests after surgery were almost twice as likely to be alive at 3 years if they received adjuvant celecoxib in addition to chemotherapy, whereas the addition of the COX2 inhibitor to chemotherapy was not associated with better disease-free survival (DFS) in ctDNA-negative patients. This insight came from a randomized trial that showed no benefit of celecoxib overall in a population not determined by ctDNA status.
A second study also showed that only ctDNA-positive patients benefited from adjuvant chemotherapy and that ctDNA clearance within 3 or 6 months predicted better DFS. Serial testing was associated with a high rate of potentially curative therapy for oligometastatic disease.
Both studies were reported at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium.
The two studies added to mounting evidence that “ctDNA is a powerful tool poised to revolutionize oncology practice,” according to invited discussant Richard Kim, MD, of the Moffitt Cancer Center in Tampa, Florida.
“However, I think that at this time the science has outpaced the clinical data, creating some uncertainty for oncologists and payers,” said Kim. “I think there’s really strong observational data supporting ctDNA as a predictive and prognostic marker, and we’re still awaiting results from ongoing phase III trials to solidify its role in clinical practice.”
Status of ctDNA is prognostic for recurrence both during molecular residual disease (MRD) and surveillance windows, he continued. “It is potentially predictive for adjuvant therapy in stage II and III colon cancer. However, details of stratification and the adjuvant regimen and duration remain to be determined. Early and intensive surveillance could potentially increase curative-intent interventions, highlighting an area that warrants further investigation.”
In the meantime, carcinoembryonic antigen assessment remains the cost-effective standard and aligns with current clinical guidelines, said Kim.
Negative Trial With ctDNA Upside
The CALGB/SWOG 80702 trial evaluated the addition of celecoxib to standard adjuvant chemotherapy in stage III CRC. The trial failed to show an improvement in DFS among patients who received the COX2 inhibitor. However, separation of the Kaplan-Meier survival curves and a final hazard ratio of 0.89 suggested a potential benefit in subgroups of patients, said Jonathan A Nowak, MD, PhD, of Dana-Farber Cancer Institute in Boston.
About 1,750 of the 2,526 patients in the trial consented to specimen collection. In a separate study, investigators generated whole-exome sequencing data for about 1,200 patients. Subsequently, 940 patients had sufficient plasma, collected after surgery but before the start of adjuvant therapy, for ctDNA testing by means of the Signatera assay. Results showed that 18.4% of the specimens were ctDNA positive.
Consistent with previous studies, ctDNA status predicted 3-year DFS, which was 86.5% in patients with ctDNA-negative tests and 33.7% among patients with positive results (P

For children with nephrotic syndrome, there was no difference in time to relapse between two commonly used non-steroid immunosuppressive medications, according to an observational study that emulated a pragmatic trial.
Among nearly 600 children, there was no significant difference in time to relapse between those taking a calcineurin inhibitor compared with those taking cyclophosphamide (HR 1.25, 95% CI 0.84-1.87, P=0.30) over a median follow-up of 5.5 years, reported Cal H. Robinson, MBChB, of the SickKids Research Institute in Toronto, and colleagues.
Although relapses were numerically higher with calcineurin inhibitors than cyclophosphamide in the weighted cohorts (85% vs 73%), the difference wasn’t statistically significant, the researchers wrote in JAMA Pediatrics.
There were also no significant differences in mean annualized estimated glomerular filtration rate slope, any subsequent steroid-sparing medication use, infection, antihypertensive medication use, and pediatric quality of life score between the two medications, but calcineurin inhibitor treatment was associated with more hospitalizations (HR 1.83, 95% CI 1.14-2.92) and intravenous albumin use (HR 2.81, 95% CI 1.65-4.81). Hospitalizations most commonly occurred within the first year of calcineurin inhibitor treatment, and 71% of hospitalized children relapsed prior to the hospitalization.
“Nephrotic syndrome is the most common kidney disease managed by pediatricians worldwide and is associated with high disease-related and treatment-related morbidity,” Robinson’s group wrote. “Nephrotic syndrome is treated initially and at each relapse with steroid immunosuppression. Currently, approximately 90% of children are steroid sensitive, but most relapse and receive repeated steroid courses.”
Because of this, half of all children with nephrotic syndrome receive non-steroid immunosuppressive medications in order to prevent relapse.
Robinson and co-authors pointed out that current guidelines recommend both cyclophosphamide and tacrolimus, but no randomized clinical trials have ever directly compared the two, largely due to “the anticipated sample size, costs, and patient and physician medication preferences.”
“This is a global health concern, since higher drug cost, limited access, and laboratory surveillance burden are major barriers to calcineurin inhibitor use in resource-limited healthcare systems,” they wrote.
“Cyclophosphamide is typically administered daily for 8 to 12 weeks, whereas calcineurin inhibitors are given for longer than 1 to 2 years with regular laboratory and therapeutic drug monitoring,” they noted. “Despite concerns about long-term infertility and cancer risks after cyclophosphamide treatment, it remains one of the most commonly prescribed immunosuppressive medications worldwide.”
As for cost differences, 2 years of tacrolimus and cyclosporine treatment are estimated to be $1,319 and $1,561, respectively, while 8 weeks of cyclophosphamide is $19 for a 44-lb child in the U.S.
Because time to relapse was similar between the two treatments, the researchers said cyclophosphamide came out on top as the preferred first-line non-steroid immunosuppressive medication due to its lower cost, shorter duration, and greater global accessibility versus calcineurin inhibitors.
For this study, the researchers emulated a pragmatic, open-label clinical trial using available data from the multicenter, prospective cohort Insight Into Nephrotic Syndrome: Investigating Genes, Health, and Therapeutics (INSIGHT) study in the greater Toronto area.
They included 578 children with steroid-sensitive nephrotic syndrome diagnosed from 1996 to 2019. Median age at diagnosis was 3.7 years, and 64% were boys. Of these patients, 252 initiated cyclophosphamide, 131 initiated calcineurin inhibitors, and 87 initiated both medications sequentially.
Cyclophosphamide was consistently used during the study period, but cyclosporine was the only calcineurin inhibitor used before 2004 and tacrolimus was most common after 2004. Median treatment duration was 9 weeks for cyclophosphamide and 2.3 years for calcineurin inhibitors.
Incidence of chronic kidney disease was low, occurring in 2.4% and 5.3% of the cyclophosphamide and calcineurin inhibitor groups, respectively.
One limitation of the trial emulation was that most children received cyclophosphamide before calcineurin inhibitors. Those who received both medications were included in both arms, with separate propensity scores calculated using updated covariates, the researchers noted. Also, some relapses may have been missed if home urine monitoring wasn’t performed and spontaneous remission occurred, or if a relapse treated at another clinical center wasn’t documented.

Kristen Monaco is a senior staff writer, focusing on endocrinology, psychiatry, and nephrology news. Based out of the New York City office, she’s worked at the company since 2015.

Disclosures
Robinson reported receiving salary support from the Cure Glomerulopathy consortium Career Development Fellowship Program, the SickKids Clinician-Scientist Training Program, and the Canadian Institutes of Health Research Fellowship Program.Co-authors reported receiving personal fees from Baxter, Getinge, Inspira, and Vasomune; a consulting agreement with Vertex and Sanofi for clinical trials in nephrotic syndrome and chronic kidney disease; and support from the Women’s College Hospital Research Institute F.M. Hill Chair in Health System Solutions.

Primary Source
JAMA Pediatrics
Source Reference: Robinson CH, et al “Comparative efficacy of nonsteroid immunosuppressive medications in childhood nephrotic syndrome” JAMA Pediatr 2025; DOI: 10.1001/jamapediatrics.2024.5286.

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Some dietary habits are worse than others when it comes to gout risk for women, a large study indicated.
Data from the two iterations of the Nurses’ Health Study, in which more than 170,000 women were followed for more than two decades, indicated that diets scoring high on the Empirical Dietary Inflammatory Pattern (EDIP) index nearly doubled the risk for new-onset gout after adjusting for body mass index (BMI), according to Natalie McCormick, PhD, of Massachusetts General Hospital in Boston, and colleagues.
Compared with the lowest quintile of EDIP scores, those in the highest quintile had a BMI-adjusted hazard ratio of 1.71 (95% CI 1.55-1.88) for incident gout, the group reported in Arthritis & Rheumatology.
McCormick and colleagues also found that, when they inverted the analysis to estimate the protective effect of diets with low EDIP scores, it was significantly greater than for top-rated diets according to two more common healthy-diet scoring systems.
And EDIP scores were markedly more relevant for women than for men: when the researchers examined data for some 45,000 men in the 30-year Health Professionals Follow-up Study, the highest EDIP quintile had only a 24% greater risk for developing gout than the lowest quintile, after BMI adjustment.
“Our findings support a role for diet-related chronic inflammation in the development of gout, similar to that seen in [cardiovascular disease and type 2 diabetes],” McCormick and colleagues wrote. “Consuming a more anti-inflammatory diet may modulate systemic and metabolic inflammation, potentially reducing gout risk and its life-threatening comorbidities, particularly for women, who are experiencing a disproportionate rise in gout burden.”
One of the group’s motivations in doing the study was the observation that gout — historically considered a men’s disease — is becoming more prevalent in women. One recent global study found age-standardized rates rising 0.38% annually for women during 1990-2017 versus 0.22% among men. Changing lifestyle behaviors are believed to be the major reason.
“Adherence to established healthy eating patterns such as the Dietary Approaches to Stop Hypertension (DASH) and the Alternative Healthy Eating Index (AHEI), each associated with lower plasma concentrations of inflammatory biomarkers, is also inversely associated with gout incidence,” McCormick and colleagues observed. “However, neither of these dietary patterns were derived specifically to predict inflammation, and research on a pro-inflammatory dietary pattern and gout remains limited.”
So the group pulled data from the original Nurses’ Health Study, which ran from 1984 to 2016, and its Nurses’ Health Study II follow-on that began in 1991 and ended in 2017. In total, these studies yielded 4,372,320 person-years of data, during which 5,425 women developed new-onset gout. These studies included detailed food-frequency questionnaires, repeated every 4 years, that allowed the researchers to score participants’ diets by EDIP, DASH, and AHEI.
Without adjusting for BMI, participants in the highest EDIP quintile developed gout at a rate 2.02 times than of the lowest quintile (95% CI 1.82-2.22). Results were similar in a sensitivity analysis when participants with pre-existing cardiovascular disease, type 2 diabetes, and malignancies were excluded.
A feature of the EDIP system is that it divides its 18 food groups into pro- and anti-inflammatory components. The former include most meat and fish varieties, refined grains, soft drinks, and tomatoes; the latter comprise beer, wine, fruit juices, dark yellow and leafy green vegetables, “snacks,” and — yes — pizza.
McCormick and colleagues recalculated EDIP scores according to their anti-inflammatory strength, and determined that the highest quintile had a hazard ratio of 0.58 (95% CI 0.53-0.65) for incident gout relative to the lowest quintile.
Corresponding hazard ratios for the top quintiles of DASH and AHEI score versus the lowest were 0.80 (95% CI 0.73-0.87) and 0.81 (95% CI 0.74-0.89), respectively.
The researchers had no definitive explanation for the finding that EDIP scores were less predictive of gout risk for men than for women, but they speculated that estrogen may play a role. “Higher estrogen levels in women may have anti-inflammatory properties under certain conditions,” they wrote, “although this effect may be lost after menopause, thereby potentially contributing to gout risk. Future prospective studies ought to replicate this observed heterogeneity.”
Limitations to the study included a lack of serum urate measurements and the potential for residual confounding; people’s recall of their dietary habits is also notoriously subject to bias. As well, study participants were well-educated and mostly white, limiting the generalizability to the female population at large.

John Gever was Managing Editor from 2014 to 2021; he is now a regular contributor.

Disclosures
The study was funded by National Institutes of Health grants. Some authors reported support from other non-commercial sources. One co-author reported additional relationships with Horizon, Ani, LG, Shanton, and Protalix.

Primary Source
Arthritis & Rheumatology
Source Reference: Rai SK, et al “Pro-inflammatory dietary pattern and the risk of female gout: sex-specific findings from three prospective cohort studies” Arthritis Rheumatol 2025; DOI: 10.1002/art.43127.

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Handy is a pediatric infectious diseases physician and an assistant professor of clinical pediatrics.

It was 11 p.m. and I had just fallen asleep when I heard a cry from my 4-year-old son’s room. I headed downstairs to find a trail of vomit on the carpet and up the stairs, as he tried to make his way up to my bedroom. The next few hours were a blur as I rushed him back and forth to the bathroom. The second time he got sick, he vomited directly into my hands, onto my robe, in my hair. As frantically as I worked to scrub my hands and face with soap and water and get all the clothes and bedding into the laundry, I knew I would be the next person to experience norovirus in the house.
How could I be certain? The spread of norovirus is quick and efficient.
Many factors contribute to its spread:Infectious dose: With just 100 (or fewer) viral particles, norovirus can infect the next person. Considering there is somewhere between 1-100 million particles in just 1 milliliter of vomit, only a small amount is needed to pass on the infection.Stability in the environment: Norovirus is hardy due to its hard protein shell. It is resistant to extreme temperatures, lives for days to weeks, and is resistant to many common cleaning agents, including alcohol-based hand sanitizers. If an infected person vomits in the bathroom (or elsewhere), every contaminated surface must be cleaned with a disinfectant (typically bleach) that can effectively kill norovirus.Transmission routes: Norovirus spreads through the fecal oral route, aerosolized particles from vomiting, and any close contact with viral particles on a countertop or doorknob.
As predicted, about 40 hours later — the incubation period is 12-48 hours, allowing the virus to spread rapidly in crowded locations — I became ill. Despite having had norovirus in the past, immunologic memory is often short-lived compared to some other viruses, and prior memory from a different strain may not be protective. My daughter’s symptoms followed 6 hours after mine, likely from the carpet I couldn’t sanitize, the doorknob I didn’t scrub well enough, or simply from playing with her brother the next day, who is still learning hand hygiene. Even if symptoms quickly resolve, people continue to shed virus. This means that one ineffective post-restroom hand wash the day (or week) after illness can lead to ongoing spread.
Managing the Symptoms
My son was more miserable than my daughter, asking for tummy medicine or a glass of water. I had no anti-emetics in the cabinet and his dry red lips showed his dehydration. I told him to take one sip from the cup next his bed to begin rehydrating. Unfortunately, he gulped down about 6 ounces, which he promptly vomited back up. We changed tactics to a small medicine cup with an ounce of Pedialyte and then set a timer for 15 minutes. Once he kept that down, we continued with small ounce cups every 5-15 minutes.
Age-specific oral rehydration (ORT) therapy is best done with a fluid with salt and sugar — Pedialyte, a diluted sports drink, or even diluted apple juice. Anti-emetics may help with dehydration, particularly if a patient is unsuccessful with ORT at home. Protocols in medical settings that include early use of medications like ondansetron (Zofran) coupled with ORT demonstrate shorter visits and decreased use of IV fluids. Similarly, antidiarrheal medications may help reduce fluid losses after the acute illness while the intestinal track begins to heal. Some patients may be able to tolerate a normal diet within a day, while others may have post-infectious symptoms that require diet modification while the gastrointestinal (GI) tract is recovering.
Sharing this guidance with patients, or parents of patients, can guide their recovery.
Why Are We Seeing More Cases This Year?
Our home was just a microcosm of the current environment. In January 2025, the rate of norovirus test positivity reported by a U.S. lab network was more than twice as high as last season, and may be peaking earlier than prior seasons. This is attributed to the presence of a new strain, GII.17[P17]. In seasons when a new strain circulates, the country can see a large increase in cases compared to typical seasons, spiking earlier than usual.
Staying Safe in the Hospital
Norovirus spreads through households, in crowded settings like daycares and cruise ships, through contaminated food, and unfortunately, at the workplace — including the hospital. Recall that only 100 particles of virus are needed to spread to another person.
Take this scenario: You’ve just examined a baby dehydrated from norovirus and adjusted their diaper, which is teeming with virus. After the visit, you use alcohol-based hand rub instead of soap and water. Particles survive on your hands. You grab a handful of M&Ms from the hospital break room candy bowl before the next patient. Not only are you likely to become sick, but with the candy bowl contaminated, the next few employees to grab handfuls of M&Ms are likely to become symptomatic as well.
How do you stop spread through the hospital?Practice meticulous hand hygiene. This is essential. Wash hands with soap and water instead of alcohol-based hand rub for a full 20-30 seconds after caring for patients with GI illness, before eating, after using the restroom, and before preparing food.Identify patients with gastrointestinal symptoms and follow your hospital’s practices for testing and isolation. Isolation practices can be symptom-based, and testing can be used to identify trends in your community or outbreaks in your institution that may alter your infection prevention practices.Follow and share food safety guidance. Eat and drink only in non-patient care areas. Avoid finger foods or shared snacks. Have hand hygiene available in hospital break rooms.Pay attention to your personal protective equipment. Use standard precautions to protect yourself whenever changing a diaper. If you mask during patient care, change your mask after caring for a patient who has gastroenteritis or is actively vomiting, as it can be contaminated.Ensure your care areas are easy to clean. Minimize clutter and have disinfectants readily available with a norovirus kill claim.Stay home when sick. Ensure your practice has a robust sickness policy that supports employees staying home when sick. If possible, have employees report GI symptoms to understand if you have spread in your hospital.
Avoiding Norovirus Is Possible
Remarkably, in our household of norovirus sufferers, my husband remained unscathed — or at least asymptomatic. How? He recalled my vivid descriptions of norovirus’s stealthy spread in the workplace: bowls of popcorn and bags of Skittles, contaminated by a single unwashed hand, infecting an entire group. Motivated by this knowledge, he diligently practiced impeccable hand hygiene, ran endless loads of laundry, and obsessively sanitized every surface we touched.
His efforts served as a reminder that while norovirus is notoriously contagious, its spread is not inevitable. With vigilance and prevention, even norovirus can be contained.
Lori Handy, MD, MSCE, is associate director of the Vaccine Education Center and an attending physician in the Division of Infectious Diseases at the Children’s Hospital of Philadelphia (CHOP). She is also an assistant professor of Clinical Pediatrics at the Perelman School of Medicine.

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For recurrent respiratory papillomatosis (RRP), novel gene therapy to jump-start immunity to the human papillomavirus (HPV) that causes it was safe and yielded complete response in many cases, a small pivotal trial showed.
Fully 51% (18) of the 35 patients treated at the recommended phase II dose of PRGN-2012 had a complete response, defined by no clinically indicated interventions in the year following treatment.
Notably, these patients had required a median of four and up to 10 laser ablation or surgical procedures to treat the recurrent disease in the 12 months before the trial, reported researchers led by Scott Norberg, DO, of the NIH Center for Immuno-Oncology in Bethesda, Maryland.
The median duration of complete response was yet to be reached at 12-month follow-up, and 83% (13) of the 18 responders remained so beyond the 12 months to a median follow-up of 22 months.
While just a single-center, single-arm, phase I/II trial, it will be the basis for application to the FDA for accelerated approval as the first systemic treatment for RRP in adults, the researchers noted in their paper in Lancet Respiratory Medicine.
Spontaneous change in the tempo of surgeries due to improvement in the condition is unlikely, so the results are “highly likely” to be due to the gene therapy, noted an accompanying editorial by Craig Derkay, MD, of Eastern Virginia Medical School in Norfolk.
“This is a potentially game-changing treatment for adults with severe RRP, which is a very challenging disease to treat and exacts a tremendous toll on patients through the requirement for repeated surgeries,” he wrote. “Any new clinical intervention that reduces the need for surgery is a breakthrough because no current therapeutics are licensed for treatment of this disorder.”
Chronic infection with HPV subtypes 6 and 11 is responsible for the vast majority of RRP, which is considered rare at an incidence of two per 100,000 persons in the United States. The condition causes persistent papillomas predominantly in the larynx, trachea, and lungs. Standard treatment — repeated laser ablation and surgical excision of papillomas — to preserve the larynx and a patent airway can cause irreversible airway damage over the hundreds of procedures patients may require over their lifetime.
Previous attempts with nonspecific immunotherapies, such as systemic interferon or immune checkpoint blockade, haven’t panned out in RRP, Derkay noted.
The trial serves as “proof-of-concept that T cells that are HPV-specific are activated to directly attack the papillomas,” he wrote. PRGN-2012 uses a gorilla adenovirus vector to deliver gene therapy to elicit robust T-cell immunity specific to HPV 6 or 11. A second gene therapy candidate that spurs antigen-specific T cell response against both HPV-6 and HPV-11 proteins showed a nearly 50% complete response rate at 1 year in a phase II study done by Inovio.
“A novel approach using immunotherapy might eventually allow for cure of RRP and other HPV-mediated disease,” Derkay suggested.
In the trial, patients got standard surgery for the disease at baseline and then four subcutaneous administrations of adjuvant PRGN-2012 over the course of 12 weeks, with up to two optional debulking surgeries to maintain minimal residual disease if papilloma regrew during this period. Both the initial surgery and any needed to maintain minimal residual disease were performed at the NIH Clinical Center by a single surgeon.
Need for pretrial interventions and those more than 12 months after treatment were determined by the patient’s usual-care otolaryngologist without involvement of the study team.
The 35 patients (57% male) treated at the recommended phase II dose (out of a total 38 treated across the phase I and II trials) had been diagnosed at a median 35 years of age and started treatment at a median of 49 years.
Most of the participants (66%) had adult-onset disease, but the response rate was similar between them and those with juvenile-onset RRP.
No serious adverse events, grade 3 or worse treatment-related adverse events, or early treatment discontinuations occurred. Most adverse events were mild; most common among them were grade 1-2 injection site reactions (97%), fatigue (80%), chills (71%), and fever (69%).
One death from cardiogenic shock following myocardial infarction was deemed due to a previous history of coronary artery disease and severe aortic stenosis rather than the study drug.
One limitation of the trial was lack of biopsy of visibly normal laryngeal mucosa to determine whether HPV infection was completely cleared in patients with complete responses. “Therefore, it is unknown whether these patients have been cured,” the researchers noted. “Longer follow-up will help determine whether the clinical course of RRP has been permanently affected by PRGN-2012 treatment.”
Phase III trials are being planned to confirm durability of the results with both PRGN-2012 and the Inovio agent and to determine if a booster dose might help or what factors differentiate those who don’t respond, Derkay noted.
“Future studies looking at whether combination therapies with additional systemic agents (immune-checkpoint inhibitors or bevacizumab [Avastin] biosimilars) might alter the papilloma microenvironment to become more supportive of HPV-specific T-cell immunity, potentially resulting in a greater proportion of patients with RRP reaching durable disease control, will be the focus of ongoing research,” he added.

Disclosures
The work was funded by the National Cancer Institute (NCI)’s Intramural Research Programs of the Center for Cancer Research and by a cooperative research and development agreement between NCI and Precigen.Norberg disclosed no relevant relationships with industry. Trial co-authors disclosed relationships with Precigen and the National Institutes of Health; one is a holder of a patent for HPV vaccines and another reported other related patents planned, issued, or pending.Derkay had no disclosures.

Primary Source
The Lancet Respiratory Medicine
Source Reference: Norberg SM, et al “PRGN-2012 gene therapy in adults with recurrent respiratory papillomatosis: a pivotal phase 1/2 clinical trial” Lancet Respir Med 2025; DOI: 10.1016/S2213-2600(24)00368-0.

Secondary Source
The Lancet Respiratory Medicine
Source Reference: Derkay CS “A high-impact study and landmark achievement in the treatment of recurrent respiratory papillomatosis” Lancet Respir Med 2025; DOI: 10.1016/ S2213-2600(24)00424-7.

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Fred Pelzman is an associate professor of medicine at Weill Cornell, and has been a practicing internist for nearly 30 years. He is medical director of Weill Cornell Internal Medicine Associates.

What could we do with $5 trillion?
Apparently, we do a lot, and yet sometimes it seems like it’s just not enough.
This amount is an approximation of the U.S. annual healthcare spending, nearly 18% of the national GDP, which gives us probably the most expensive healthcare in this world without giving our citizens the best health. We spend and we spend and we spend, and then we spend more trying to figure out why what we spent didn’t work.
In a recent article in the New York Times, a report from Britain on the state of their National Health Service decried the terrible prognosis of their beloved healthcare system, from the point of view of the beleaguered, overwhelmed, and burned-out nurses desperately trying to take care of patients. Patients piled in hospital corridors. Patients denied their dignity. Patients dying for lack of timely and compassionate care. Everyone there — as well as most everyone here — seems to be in a place that is not the best place for taking care of human beings.
How have we allowed such a system to be built up around us that costs more and delivers less?
Doctors, nurses, and every member of the healthcare team — we went into our fields because we love taking care of people. We love this job, and we want to do what’s best for our patients. Over and over, we hear about different models of innovation, new structures that someone came up with to rethink how to deliver care. With all this money we’re spending, wouldn’t it be great if we could flip things on their heads, if those of us in healthcare could decide what things cost, what to spend it on, and how to get everyone paid what they deserve?
Every day, we hear stories, either from our family or friends, or from patients who come in to see us, telling us about a terrible healthcare experience. Lack of access to care and mind-numbing delays, inequitable care, miscommunication or no communication, over-testing and over-diagnosing, waste upon waste upon waste, doctors and nurses spending hours staring at their computer screens creating documentation instead of caring for the patients in front of them.
Working around the margins, re-creating the wheel with some new system to give providers a few more pennies per patient per month to fill out more forms, click on more boxes in the electronic medical record, and ask them to try to do more work without the right tools and adequate resources, probably isn’t going to make anybody better.
True, there is so much more than what we do in healthcare that directly impacts our patient’s health, from the neighborhoods they live in, their safety, their access to clean water and healthy foods, safe places to exercise, and a decent job and education. Clearly fixing the healthcare system locally, even if we were to do it across the entire country, will never be enough to overcome these other obstacles. But if we built a system based on the ideas that doctors, nurses, social workers, mental health providers, community advocates, and patient activists have for the best ways to take care of people, we’d probably be a lot better off.
Returning us to a day where everyone had a primary care doctor who knew them and took care of them through the days of their lives, helping them to get and stay healthy, helping them overcome acute health challenges and manage chronic health issues, and getting them all the care they need — the right care at the right time — could go a long way.
From prenatal care through end-of-life care, from preventive medicine to surgery or chemotherapy for catastrophic illnesses, if we built a system that works smoothly, that gave us the almost limitless resources that $5 trillion should afford us, then we would probably be a lot better off than we are today, and we’d probably have a nice chunk of change left over.
Someone once told me the difference between a millionaire and a billionaire. If I gave you $1,000 a day, before 3 years were up, you’d have $1 million — you’d be a millionaire. But if I gave you that same $1,000 a day, starting in the year 0, you’d still have a couple of hundred years to go before you amassed $1 billion. And that’s only a billionaire. The concept of a trillion dollars (let alone five), is just so big we can probably never really get our heads around it.
So I’m thinking that with $5 trillion, under this kinder and gentler healthcare system that we can envision in the future, we can spend and spend on prevention, access to care, cheaper medications, unlimited mental health care, and equitable pay for every member of the healthcare team so they can live and thrive and come to work each day with joy in their hearts.
Then it’s up to the rest of society to take care of the rest of the stuff, the other social determinants of health, the things that are barriers to our patients succeeding once they leave our offices.
The bill comes due.

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SAN FRANCISCO — An immunotherapy combination for advanced, highly mutated colorectal cancer (CRC) significantly slowed disease progression versus a single drug, according to a randomized study.
Median progression-free survival (PFS) had yet to be reached with nivolumab (Opdivo) plus ipilimumab (Yervoy) after 47 months of follow-up as compared with a median of 39.3 months with nivolumab, which translated into a 38% risk reduction. Subgroup analyses revealed a consistent benefit of the combination versus monotherapy in the population of patients with centrally confirmed microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) tumors.
More grade 3/4 treatment-related adverse events (AEs) occurred with the combination, but these did not reduce quality of life (QoL), reported Thierry Andre, MD, of Sorbonne University and Saint Antoine Hospital in Paris, in presenting the data at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium.
“These results, combined with the previously reported superiority, with nivolumab plus ipilimumab versus chemotherapy in the first-line setting established nivolumab-ipilimumab as a new standard of care for patients with MSI-H/dMMR metastatic colorectal cancer,” said Andre.
Findings from the CheckMate 8HW study were published simultaneously in The Lancet.
The phase III trial showed a clear benefit with the combination, achieved with a fairly low rate of AEs, particularly grade 3/4 and serious AEs, said ASCO-invited discussant Wells Messersmith, MD, of the University of Colorado Cancer Center in Aurora. The same was true of immune-related AEs, as a total of 28 additional grade 3/4 events occurred in the combination arm.
“Now some of these can be difficult to manage, and if you’re the patient, they can feel quite severe,” said Messersmith, who evaluated the findings within the context of a hypothetical patient with an MSI-H/dMMR tumor. “But we usually are able to manage these, and the improvement in quality-of-life scores was also quite encouraging.”
Several issues related to the combination therapy remain unresolved, he added. Elucidation of the disease biology might provide insights into the management of patients with microsatellite-stable tumors, which are more prone to liver metastases. The optimal duration of treatment with each drug has yet to be determined as well. Finally, are two drugs always necessary, or can treatment begin with one drug and escalate to two at a later date?
MSI-H/dMMR tumors account for 4-7% of CRCs and are associated with poor outcomes when treated with chemotherapy plus targeted agents, Andre noted in discussing the background of the study. Single-agent pembrolizumab (Keytruda) improved PFS in MSI-H/dMMR CRC in the first-line setting, but 29% of patients had primary progressive disease. PFS at 2 and 5 years was 48% and 34%, respectively, leaving a substantial unmet need.
Indirect comparisons involving data from the phase II CheckMate 142 trial suggested nivolumab plus ipilimumab provided better outcomes than did single-agent nivolumab. The phase III CheckMate 8HW trial continued evaluation of nivolumab/ipilimumab in patients who were immunotherapy-naive with advanced MSI-H/dMMR CRC, comparing the combination with either nivolumab alone or chemotherapy with or without targeted drugs.
The trial had two primary endpoints: PFS by blinded independent review for the combination versus physician’s choice of chemotherapy in the first-line setting (previously reported), and PFS by blinded independent review for nivolumab/ipilimumab versus nivolumab across all lines of treatment. Andre reported findings from the comparison of the combination versus single-agent nivolumab.
The two arms had a combined total of 707 patients who had a median age of 62-63. The combination arm had a higher proportion of women compared with the nivolumab arm (54% vs 46%). A quarter of the patients had received two or more prior lines of therapy.
Median duration of therapy was 20.5 months for the combination and 16.4 months with single-agent nivolumab. Median number of treatment cycles with nivolumab was 23 in the combination arm and 21 in the nivolumab arm. More than 80% of patients in the combination arm received the planned four cycles of ipilimumab.
After a median follow-up of 47 months, the combination demonstrated a statistically significant and clinically meaningful benefit in the 582 patients with centrally confirmed MSI-H/dMMR status (HR 0.62, 95% CI 0.48-0.81, P=0.0003). In the combination arm, the lower limit of the 95% confidence intervals for PFS was 53.8 months while the median value for the nivolumab arm was 39.3 months (95% CI 22.1 to not estimable). The combination also prevailed in an analysis of all randomized patients (median PFS 54.1 vs 18.4 months), said Andre. The PFS benefit with the combination was consistent across all prespecified subgroups.
The objective response rate was 71% with the combination and 58% with nivolumab (P=0.0011). Median duration of response had yet to be reached in either treatment arm.
All-grade, treatment-related AEs occurred in 81% of the combination-arm patients and 71% among patients randomized to single-agent nivolumab. Grade 3/4 treatment-related AEs occurred in 22% versus 14% of patients, and serious treatment-related AEs in 18% versus 8%. The most frequent treatment-related AEs (all grades) were the same in both treatment arms: pruritus, diarrhea, hypothyroidism, asthenia, and fatigue. Immune-mediated AEs also occurred more often with the combination, but toxicity was consistent with known effects of the drugs.
QoL, as assessed by a global health quality instrument, improved over time and did not differ significantly between treatment groups.

Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined MedPage Today in 2007. Follow

Disclosures
CheckMate 8HW was supported by Bristol Myers Squibb.Andre disclosed relationships with Bristol Myers Squibb, Merck, Merck Serono, Sanofi, Seagen, Servier, AbbVie, Aptitude Health, Gilead, GSK, MSD Oncology, Nimbus Therapeutics, Nordic Bioscience, Pfizer, and Takeda.Messersmith disclosed relationships with Research to Practice, Amgen, Criterium, Agenus, ALX Oncology, AstraZeneca/MedImmune, BeiGene, CanBas, Exelixis, FATE Therapeutics, Mirati Therapeutics, Nurix, Pfizer, PureTech, RasCal, and Revolution Medicine.

Primary Source
ASCO Gastrointestinal Cancers Symposium
Source Reference: Andre T, et al “First results of nivolumab plus ipilimumab vs nivolumab monotherapy for microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer from CheckMate 8HW” ASCO GI Cancers 2025; Abstract LBA143.

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