Tumor microbiome interactions may ID new approaches for pancreatic cancer treatment

 Investigators from Rutgers Cancer Institute of New Jersey, the state's leading cancer center and only National Cancer Institute-Designated Comprehensive Cancer Center, together with RWJBarnabas Health, examined the microbiome of pancreatic tumors and identified particular microorganisms at single cell resolution that are associated with inflammation and with poor survival. According to the researchers, these microorganisms may be new targets for earlier diagnosis or treatment of pancreatic cancer, which is the fourth leading cause of cancer death for both men and women in the United States. The findings are published in the online version of Cancer Cell.

Microbes are living things that are too small to be seen with the naked eye. We have more microbes living in our body than the total number of human cells, and can be found in organs like the pancreas, which at one time was considered microbe-free. Subhajyoti De, PhD, principal investigator at Rutgers Cancer Institute and senior author of the study along with graduate student Bassel Ghaddar, a student in the MD/PhD program at Rutgers Robert Wood Johnson Medical School, began exploring if there are microbes residing in pancreatic tumors, and if they have consequences for cancer progression or treatment. However, studying microbes in tumors is difficult, in part since every patient is different, and because microbial footprints are too subtle to detect reliably.

To explore further, the researchers teamed up with Martin Blaser, MD, Henry Rutgers Chair of the Human Microbiome at Rutgers University and microbiome expert. The investigators developed a genomic approach called SAHMI (Single-cell analysis of Host-Microbiome Interactions) to identify microorganisms associated with individual human cells. Sifting through millions of RNA sequences using sophisticated software, they identified which ones likely represent human genes, and which ones are microbial in origin. "This new technique allowed us to identify tumor-associated microbes and measure the activity of the host cells at the same time, which is a significant technical advance, and the results were stunning," notes Dr. De, who is also an associate professor of cancer systems biology at Rutgers Robert Wood Johnson Medical School.

Studying two independent groups of pancreatic tumors, the team found that some had bacteria that associated with specific cell-types within the tumor, which were essentially absent in normal pancreatic tissues. These bacteria were predominantly located within tumor cells, and their abundance correlated with cancer-related cell activities. The specific signatures of the microbes that were found predicted particularly aggressive cancer progression and poor prognosis.

The microbial footprints within the pancreatic tumors raised the question of whether the immune cells that were present were responding to the cancer or to the microbes. The study findings suggested that the immune responses were mostly responding to the microbes in the tumor and not to the cancer cells. "Our observations provide a new view about why pancreatic cancers are so difficult to treat," notes Dr. Blaser, who is also a research member at Rutgers Cancer Institute and professor of epidemiology and biostatistics at Rutgers School of Public Health. "But better understanding these interactions may identify new approaches for therapies."

Along with Drs. De, Ghaddar, and Blaser, other investigators include: Antara Biswas, PhD, Center for Systems and Computational Biology, Rutgers Cancer Institute; Chris Harris, PhD, Department of Surgery, University of Rochester Medical Center; M. Bishr Omary, PhD, Center for Advanced Biotechnology and Medicine, Rutgers University and Darren R. Carpizo, MD, PhD, Department of Surgery, University of Rochester Medical Center.

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Story Source:

Materials provided by Rutgers University. Note: Content may be edited for style and length.

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Journal Reference:

1. Bassel Ghaddar, Antara Biswas, Chris Harris, M. Bishr Omary, Darren R. Carpizo, Martin J. Blaser, Subhajyoti De. Tumor microbiome links cellular programs and immunity in pancreatic cancer. Cancer Cell, 2022; 40 (10): 1240 DOI: 10.1016/j.ccell.2022.09.009

https://www.sciencedaily.com/releases/2022/10/221010115335.htm

Dutch Right-To-Die Group Fights to Widen Legal Euthanasia Boundaries

 A right-to-die group told judges on Monday that a Dutch law which allows physician-assisted suicide in the Netherlands but criminalises others who help people end their own lives violates European human rights law and must be declared unlawful.

"We believe it should be possible to provide the means to be able to humanely end your own life," Jos van Wijk of Cooperative Last Will said in court.

Marion van Gerrevink, whose 22-year-old son took his own life in 2010, told judges she struggled with feelings that she let her son down because she couldn't help him find a humane and dignified way to die for fear of prosecution.

"He had to take that last step utterly alone," Gerrevink, one of the 29 plaintiffs who joined the case, said.

A lawyer for the cooperative said the case is strategic litigation aimed at forcing the Netherlands to change the laws.

They argue that the current ban on assisting suicide not overseen by medical professionals violated the right to self-determination and respect for private life enshrined in the European convention on human rights.

Lawyers for the Dutch state argued that the euthanasia laws strike good balance between the duty of the state to protect citizens, even from themselves, and individual autonomy.

The Netherlands was the first country in the world to legalise euthanasia and physician-assisted suicide under very strict conditions and when overseen by medical professionals.

Assisting a suicide, or providing a means to commit suicide outside of the strict euthanasia criteria, is punishable with a jail term of up to three years.

Cooperative Last Will has been promoting a suicide powder it calls "Substance X" since 2018. There is a separate ongoing case before the Dutch courts against a member of the cooperative who is suspected of illegally assisting suicide by selling "Substance X" to at least 33 people.

A ruling is expected on Dec. 14, the judges said.

https://www.usnews.com/news/world/articles/2022-10-10/dutch-right-to-die-group-fights-to-widen-legal-euthanasia-boundaries

Bio-Rad in talks to merge with Qiagen

 California-based diagnostics company Bio-Rad Laboratories is in talks to merge with Qiagen NV , according to a Wall Street Journal report on Monday. 

https://finance.yahoo.com/news/diagnostics-firm-bio-rad-talks-181424568.html

Like Texting and Driving: The Human Cost of AI

 A recent medical meeting I attended included multiple sessions on the use of artificial intelligence (AI), a mere preview, I suspect, of what is to come for both patients and physicians.

I vow not to be a contrarian, but I have concerns. If we'd known how cell phones would permeate nearly every waking moment of our lives, would we have built in more protections from the onset?

Although anyone can see the enormous potential of AI in medicine, harnessing the wonders of it without guarding against the dangers could be paramount to texting and driving. 

A palpable disruption in the common work-a-day human interaction is a given. CEOs who mind the bottom line will seek every opportunity to cut personnel whenever machine learning can deliver. As our dependence on algorithms increases, our need to understand electrocardiogram interpretation and echocardiographic calculations will wane. Subtle case information will go undetected. Nuanced subconscious alerts regarding the patient condition will go unnoticed.

These realities are never reflected in the pronouncements of companies who promote and develop AI.

The 2-Minute Echo

In September 2020, Carolyn Lam, MBBS, PhD, and James Hare, MBA, founders of the AI tech company US2.AI, told Healthcare Transformers that AI advances in echocardiology will turn "a manual process of 30 minutes, 250 clicks, with up to 21% variability among fully trained sonographers analyzing the same exam, "into an "AI-automated process taking 2 minutes, 1 click, with 0% variability."  

Let's contrast this 2-minute human-machine interaction with the standard 20- to 30-minute human-to-human echocardiography procedure.

Take Mrs. Smith, for instance. She is referred for echocardiography for shortness of breath. She's shown to a room and instructed to lie down on a table, where she undergoes a brief AI-directed acquisition of images and then a cheery dismissal from the imaging lab. Medical Corporate CFOs will salivate at the efficiency, the decrease in cost for personnel, and the sharp increase in put-through for the echo lab schedule.

But what if Mrs. Smith gets a standard 30-minute sonographer-directed exam and the astute echocardiographer notes a left ventricular ejection fraction of 38%. A conversation with the patient reveals that she lost her son a few weeks ago. Upon completion of the study, the patient stands up and then adds, "I hope I can sleep in my bed tonight." Thinking there may be more to the patient's insomnia than grief-driven anxiety, the sonographer asks her to explain. "I had to sleep in a chair last night because I couldn't breathe," Mrs. Smith replies.    

The sonographer reasons correctly that Mrs. Smith is likely a few weeks past an acute coronary syndrome for which she didn't seek attention and  is now in heart failure. The consulting cardiologist is alerted.  Mrs. Smith is worked into the office schedule a week earlier than planned, and a costly in-patient stay for acute heart failure or worse is avoided.

Here's a true-life example (some details have been changed to protect the patient's identity):

Mr. Rodriquez was referred for echocardiography because of  dizziness. The sonographer notes significant mitral regurgitation and a decline in left ventricular ejection fraction from moderately impaired to severely reduced. When the sonographer inquires about a fresh bruise over Mr. Rodriguez's left eye, he replies that he "must have fallen, but can't remember."

The sonographer also notes runs of nonsustained ventricular tachycardia on the echo telemetry, and after a phone call from the echo lab to the ordering physician, Mr. Rodriquez is admitted.  Instead of chancing  a sudden death at home while awaiting follow-up, he undergoes catheterization and gets an implantable cardioverter defibrillator.

These scenarios illustrate that a 2-minute visit for AI-directed acquisition of echocardiogram images will never garner the protections of a conversation with a human. Any attempts at downplaying the importance of these human interactions are misguided.

Sometimes we embrace the latest advances in medicine while failing to tend to the most rudimentary necessities of data analysis and reporting. Catherine M. Otto, MD, director of the heart valve clinic and a professor of cardiology at the University of Washington Medical Center, Seattle, is a fan of the basics.

At the recent European Society of Cardiology (ESC) Congress, she commented on the AI-ENHANCED trial, which used an AI decision support algorithm to identify patients with moderate to severe aortic stenosis, which is associated with poor survival if left untreated. She correctly highlighted that while we are discussing the merits of AI-driven assessment of aortic stenosis, we are doing so in an era when many echo interpreters exclude critical information. The vital findings of aortic valve area, Vmax, and ejection fraction are often nowhere to be seen on reports. We should attend to our basic flaws in interpretation and reporting before we shift our focus to AI.

Flawed Algorithms

Incorrect AI algorithms that are broadly adopted could negatively affect the health of millions.

Perhaps the most unsettling claim is made by causaLens: "Causal AI is the only technology that can reason and make choices like humans do," the website states. A tantalizing tag line that is categorically untrue.

Our mysterious and complex neurophysiologic function of reasoning still eludes understanding, but one thing is certain: medical reasoning originates with listening, seeing, and touching.

As AI infiltrates mainstream medicine, opportunities for hearing, observing, and palpating will be greatly reduced.

Folkert Asselbergs from University Medical Center Utrecht, the Netherlands, who has cautioned against overhyping AI, was the discussant for an ESC study on the use of causal AI to improve  cardiovascular risk estimation.

He flashed a slide of a 2019  Science article on racial bias in an algorithm that U.S. healthcare systems use.  Remedying that bias "would increase the percentage of Black people receiving additional help from 17.7% to 46.5%," according to the authors.  

Successful integration of AI-driven technology will come only if we build human interaction into every patient encounter.

I hope I don't live to see the rise of the physician cyborg.

Artificial intelligence could be the greatest boon since the invention of the stethoscope, but it will be our downfall if we stop administering a healthy dose of humanity to every patient encounter.  

Melissa Walton-Shirley, MD, is a native Kentuckian who retired from full-time invasive cardiology. She enjoys locums work in Montana and is a champion of physician rights and patient safety.

https://www.medscape.com/viewarticle/982119

Is Another COVID-19 Booster Really Needed?

 Many countries around the globe are starting to roll out another booster of the COVID-19 vaccine but, with public interest waning and a sense of normalcy firmly installed in our minds, this may prove an ill-fated effort, unless authorities can provide a coherent answer to the question "Is another jab really needed?" (The short answer is a firm "yes," of course.)

In what we could call the "chronic" phase of the pandemic, most countries have now settled for a certain number of daily cases and a (relatively low) number of complications and deaths. It's the vaccines that have afforded us this peace of mind, lest we forget. But they are different to other vaccines that we are more familiar with, such as the MMR that we get as kids and then forget about for the rest of our lives. As good as the different COVID-19 vaccines are, they never came with the promise of generating lifelong antibodies. We knew early on that the immunity they provide slowly wanes with time. That doesn't mean that those who have their vaccination records up-to-date (which included a booster probably earlier this year) are suddenly exposed. Data suggest that although people several months past their last booster would now be more prone to getting reinfected, the protection against severe disease still hangs around 85%. In other words, their chances of ending up in the hospital are low.

Why worry, then, about further boosting the immune system? The same studies show that an additional jab would increase this percentage up to 99%. Is this ~10% improvement really worth another worldwide vaccination campaign? Well, this is a numbers game, after all. The current form of the virus is extremely infectious, and the Northern Hemisphere is heading toward the cold months of the year, which we have seen in past years increases COVID-19 contagions, as you would expect from any airborne virus. Thus, it's easy to expect a new peak in the number of cases, especially considering that we are not going to apply any of the usual restrictions to prevent this. In these conditions, extending the safety net to a further 10% of the population would substantially reduce the total number of victims. It seems like a good investment of resources.

We can be more surgical about it and direct this new vaccination campaign to the population most likely to end up in the hospital. People with concomitant pathologies are at the top of the list, but it's also an age issue. On the basis of different studies of the most common ages of admission, the cut-off point for the booster varies from country to country, with the lowest being 50 and in other cases hovering around 65 years of age. Given the safety of these vaccines, if we can afford it, the wider we cast the net, the better, but at least we should make every effort to fully vaccinate the higher age brackets.

The final question is which vaccine to give. There are confounding studies about the importance of switching to Omicron-specific jabs, which are finally available. Although this seems like a good idea, since Omicron infections elicit a more effective range of antibodies and new variants seem to better escape our defences, recent studies suggest that there actually may not be so much difference with the old formula.

The conclusion? Vaccinate the elderly (and some middle-aged too, if possible) and the frail as soon as possible with any version of the booster you have available, if you want to keep hospital pressure to the minimum and save a fair number of complications and deaths over the next months. This regimen of yearly boosters for some may be the scenario for the upcoming years, similar to what we already do for the flu, so we should get used to it.

Salvador Macip, MD, PhD is a doctor, researcher and writer. He obtained his MD/PhD at the University of Barcelona (Spain) in 1998, then moved to do oncological research at the Mount Sinai Hospital (New York). Since 2008, he has led the Mechanisms of Ageing and Cancer Lab at the University of Leicester (UK). Macip has published over 30 books, including Where Science and Ethics Meet (2016) and Modern Epidemics (2021). 

https://www.medscape.com/viewarticle/981614

Physicians Less Likely to Accept New Patients With Opioid Use Disorder

 Family physicians are almost three times less likely to offer a new patient appointment to a patient with opioid use disorder (OUD), compared with a patient with diabetes, new data from Ontario, Canada suggest.

In a randomized clinical trial that included almost 400 family physicians, those with more than 20 years' experience were almost 13 times less likely to offer an appointment to a patient with OUD than to a patient with diabetes.

Dr Sheryl Spithoff

"We knew from previous work that we had done here in Ontario, and that people have done in other places, that people with addictions, in particular addictions to opioids, are less likely to have a family doctor or primary care provider," study author Sheryl Spithoff, MD, MSc, assistant professor of family and community medicine at the University of Toronto, Canada, told Medscape Medical News. "People have given different explanations as to why this may be the case, and we wondered if family doctor discretion in accepting and taking on new patients was playing a role."

The study was published September 30 in JAMA Network Open.

Generational Differences?

The investigators used an audit design to examine new patient intake at the offices of randomly selected family physicians. Eligible physicians were able to prescribe opioids and practiced within 50 km (31 miles) of a city of more than 20,000 people.

The analysis included 383 physicians who were contacted by a "patient actor" who requested an appointment. On calls with 185 physicians, the actor claimed to have diabetes and to be seeing an endocrinologist. On calls with the other 198 physicians, the actor claimed to have OUD, to be receiving methadone treatment, and to have an addiction physician.

Twenty-one of 185 physicians (11.4%) offered a new patient appointment to a caller with diabetes, and 8 of 198 (4%) offered an appointment to a caller in treatment for OUD (P = .007).

Among physicians with more than 20 years in practice, 1 of 108 (0.9%) offered an appointment to a caller with OUD, and 10 of 84 physicians (11.9%) offered an appointment to a caller with diabetes (P = .001). Family physicians who were women were nearly 5 times less likely (2.7% vs 12.3%, P = .007) to offer an appointment to a patient with OUD, compared with a patient with diabetes.

Spithoff did not explain why women family physicians were more likely to not accept a patient with OUD in their practice, but she speculated that young physicians who are early in their career, in contrast to those who are older and went to medical school years ago, have received more education about OUDs and how to manage them.

"I am thinking we need to do more work to sort out why," said Spithoff. "One hypothesis is that there is better education and training now around treating OUDs during medical school and residency, and changing societal norms, so that younger physicians are more accepting of patients with addictions and mental health problems, compared with the older generation."

The findings suggest that education and anti-oppression training are needed to address biases that family physicians may have that may be leading them to exclude a patient with an OUD from their practice, said Spithoff.

"Poverty, life challenges, loss of a job or a relationship are all things that may drive addiction," said Spithoff. Taking opioids is "something that patients with OUD are often fighting hard not to do, but these other things drive it."

In addition, the literature shows a strong association between substance use and trauma, childhood posttraumatic stress disorder, and mental health disorders like anxiety, depression, and bipolar disorder, noted Spithoff.

Developing Skill Sets

Commenting on the study for Medscape, Tara Gomes, PhD, MHSc, assistant professor of drug safety at the University of Toronto, and principal investigator of the Ontario Drug Policy Research Network, noted that it was sufficiently robust in its design.

Dr Tara Gomes

"Methodologically, I think that it was as vigorous as it can be with this kind of 'secret shopper' approach," said Gomes. "I think there were a lot of strengths in the design that I saw, such as using the same person who is calling and using a very rigorous script. They presented an alternative, which is someone with diabetes, who likely is going to have other complexities in their care."

But Gomes echoed the limitation that the investigators cited in the paper, which was that the study was conducted during the COVID-19 pandemic, which may have resulted in low rates of new patient acceptance.

The fact that more experienced physicians were much more reluctant to accept a patient with OUD in their practice may speak to a lack of comfort with managing such a patient, said Gomes.

"My interpretation of this is that perhaps those physicians who have been in practice for longer are less trained on provision of care or feel less prepared," said Gomes. "It may be that they don't think that they have the skill set to support [a patient with OUD], whereas I think more recently trained physicians might feel better prepared and able to do that."

More experienced physicians who are loath to accept patients with OUD in their practice must develop the requisite skill set and confidence to manage these patients, according to Gomes. "In my opinion, that comes back to the physician to develop that skill set and be open to learning more," she said. "Feeling uncomfortable isn't enough of a reason to create a barrier to refuse care to this population."

The study was funded by the Foundation for Advancing Family Medicine, which was established by the College of Family Physicians of Canada. Spithoff and Gomes reported no relevant financial relationships.

JAMA Netw Open. Published online September 30, 2022. Full text

https://www.medscape.com/viewarticle/982144

86% of Kids Have COVID Antibodies From Infection

 Nearly 9 in 10 kids under age 17 in the U.S. have antibodies from a previous COVID-19 infection, according to new CDC data.

As of August, 86% of children between 6 months and 17 years have had at least one COVID-19 infection, which is up from 75% in April.

"What we have to recognize is this is more of an indication that there's been broad spread of this virus in the pediatric community," John Brownstein, chief innovation officer at Boston Children's Hospital, told ABC News.

"And that, you know, the kids are not sheltered from this virus," he said. "And we know that in a small number of cases, there's severe impacts."

The latest data doesn't mean that these children and teens are protected against COVID-19 reinfections, ABC News reported. Public health researchers haven't been able to pinpoint how long the protection lasts after a previous infection.

"What we should not take away from this data is that the kids are now immune from infection, so we can't make the leap that continual investment in vaccines and protections of our kids is not important," Brownstein said. "As we know, immunity wanes and variants evolve to evade prior immunity."

The CDC recommends that everyone — regardless of prior infection — remain updated with their vaccinations, including the newest booster shot that targets the BA.4 and BA.5 Omicron variants.

The CDC also recommends that ages 12 and older receive an updated booster shot at least two months after their last vaccine dose. The original booster is available for ages 5 to 11 who have received the Pfizer-BioNTech primary vaccine series.

The Omicron-targeted booster should be available for ages 5 to 11 in mid-October, ABC News reported. In September, the FDA said the updated booster for ages 5 and younger was still "a few months away" from authorization.

The U.S. is reporting about 41,000 cases daily, according to the data tracker by The New York Times. Hospitalizations have fallen below 30,000 for the first time since June. About 400 deaths are being reported each day.

Sources

CDC: "COVID Data Tracker: Nationwide Commercial Lab Pediatric Antibody Seroprevalence."

ABC News: "86% of kids under 17 have antibodies from a past COVID infection, CDC data shows."

The New York Times: "Coronavirus in the U.S.: Latest Map and Case Count, updated Oct. 7, 2022."

https://www.medscape.com/viewarticle/982145