Advocate-Atrium merger closed without antitrust challenge. What does that mean for competition?

 Health systems have morphed into multi-regional players through acquisitions, but have evaded federal antitrust enforcement, raising questions about the future of policing merger deals.

The agency tasked with policing competition was able to thwart a number of hospital tie-ups this year, but in a closely watched deal, regulators did not challenge a megamerger between Advocate Aurora Health in the Midwest and Atrium Health in the South.

A challenge would have represented a rare attempt by the Federal Trade Commission to block a so-called “cross-market” merger in healthcare.

Instead, regulators stuck to challenging the kinds of provider deals they’ve historically contested, raising questions about its antitrust enforcement in an industry that continues to see deals evolve beyond traditional geographic markets.

“It would be reckless to take away from this that the FTC is going to cease investigating in this area,” Mike Cowie, partner at law firm Dechert, said of cross-market deals.

The FTC has successfully blocked deals between direct competitors, but cross-market deals are trickier, said Cowie, who previously led antitrust merger investigations at the FTC.

The Advocate-Atrium deal was an opportunity for the FTC to contest a health system merger with no geographic overlap. Advocate-Atrium’s facilities span six separate states and their respective hospitals do not compete with one another for the same patients in a single market.

Challenging rivals who compete in the same geographic market has been a hallmark of past FTC challenges.

Still, researchers have raised concerns about the effects that cross-market deals can have on healthcare prices.

A 2019 study found that prices can increase by as much as 10% after systems acquire hospitals in separate markets within the same state. Researchers found these providers have more leverage over insurers after combining.

But anticompetitive enforcement hasn’t caught up, researchers argued in the paper. The current methodology used to spot anticompetitive deals assumes that prices won’t increase unless providers “are vying to provide the same set of services to the same set of patients.” However, researchers argued the current thinking should be expanded to include insurers.

“Since insurers serve employers across multiple geographic regions, a merged crossmarket hospital system that covers those regions can demand higher reimbursement rates from insurers,” the researchers said.

Cross-market deals are not uncommon.

More than half of the hospital mergers between 2010 and 2012 involved hospitals or systems without facilities in the same metropolitan statistical area, the researchers said.

The Advocate-Atrium deal closed in December without a challenge from the FTC. The merger creates the fifth-largest nonprofit health system, generating annual revenue of $27 billion with 67 hospitals.

Leemore Dafny, a Harvard professor and an author on the cross-market research said, “it’s a sign that the merger wave continues and hospitals believe they are in a stronger position to succeed with more scale.”

The FTC’s healthcare challenges this year show the agency is “focusing on the devil it knows,” Pahl Zinn, an attorney at Dickinson Wright in Detroit, said.

The FTC’s current merger guidelines do not address cross-market mergers, antitrust attorneys said. The agency will need to retool their analysis to be able to address these types of situations, Zinn said. 

“Many judges rely very heavily on the merger guidelines in assessing whether a transaction is unlawful,” said Jim Burns, partner at the law firm Williams Mullen and chair of the group’s antitrust practice.

Burns likened the merger guidelines to those used for federal sentencing after people are convicted of crimes. It’s an attempt to apply a uniform standard.

Antitrust regulators are looking to modernize those guidelines, which have not been updated in 12 years. They have called on the public to submit comments as part of that effort.

The FTC did not respond to a request for comment on where it is in that process.

Still, the agency prevented numerous hospitals mergers this year.

Rhode Island’s first- and second-largest providers scrapped plans to merge after facing an FTC suit. HCA also abandoned plans to acquire its rival Steward Health Care System in Utah; and RWJBarnabas Health nixed plans to acquire Saint Peter’s Healthcare in New Jersey.

However, overall, the Biden administration has not seen much success in the antirust cases it has brought to court, which includes challenges across all sectors — beyond just healthcare.

Antitrust regulators recorded their first win in federal court under the Biden administration in October when a judge sided with the Department of Justice and blocked book publisher Penguin Random House from acquiring its rival Simon & Schuster in a $2 billion deal.

The win followed two back-to-back losses in federal court, including a loss against UnitedHealth’s acquisition of Change Healthcare. Until the win in the publishing case, “neither the DOJ nor the FTC had yet secured a win based on a complaint filed by the Biden administration in federal district court,” law firm Dechert said in its latest quarterly report on antitrust enforcement.

Regulators have had an impact even if they’ve been largely unsuccessful in court, said Burns with Williams Mullen.

“It’s probably fair to say that they have changed the way folks look at mergers,” Burns said. “I think there has been much more pre-merger reflection by merging parties.”

https://www.healthcaredive.com/news/advocate-atrium-merger-closes-antitrust-challenge-hospitals/638101/

Medtronic starts US robotic surgery trial in push to challenge Intuitive

 

• Medtronic has enrolled the first patient in a U.S. clinical trial of its Hugo robotic-assisted surgery system, advancing its push to challenge Intuitive Surgical.
• The clinical trial will enroll up to 122 patients at six sites in the U.S. to evaluate the use of Hugo in urologic procedures, a field in which Intuitive’s da Vinci robot is already well established.
• Facing an entrenched incumbent, Medtronic delayed the Hugo program to make changes in light of surgeon feedback, but now thinks it has a device that can make its mark on the sector.

Hugo is already on the market in some countries, but made a slow start commercially. Medtronic cut its sales forecast in 2021, slashing the midpoint of its range from $75 million to $30 million. Sales are now starting to ramp up, Medtronic said in its most recent financial results, but supply chain and manufacturing problems in the U.S. mean the company missed the fall 2022 launch date target it set itself in 2020.

Now, Medtronic has belatedly reached the next hurdle in its race to the U.S. market. Michael Abern recently carried out the first procedure in Medtronic’s investigational device exemption trial at Duke University Hospital, marking the start of a push to gather clinical data to support U.S. market entry.

At this stage, it is unclear how long it will take Medtronic to bring Hugo to market in the U.S. Asked for a timeline on a recent conference call with investors, Bob White, president of Medtronic’s medical surgical portfolio, demurred, saying that the timing “depends upon the agency and the process there.” White said Medtronic is “excited to be the number two player in this space.”

The timing of the launch will dictate the market conditions that Hugo faces. In recent quarters, Intuitive has seen delays to equipment purchases as hospitals reassess their capital budgets, but surgery volumes are rising. The impact of hospital staff shortages on robotics is mixed. Acute pressures cause volumes to fall, but overall the situation can favor robotics because it reduces staffing requirements post-surgery.

https://www.healthcaredive.com/news/medtronic-MTD-robotic-surgery-clinical-trial-hugo/639377/

When Will Academia Account for Its Covid Failures?

 Many in America’s academic class betrayed the public trust during the pandemic. To sway the American people to accept lockdowns, professors with prestigious titles and affiliations denied scientific data about risks, effective mitigation and biological protection. They spouted politicized opinion as if it were objective truth and demonized views counter to their preferred narrative.

In February 2020, the Lancet published a letter from some of America’s most famous university virologists condemning as “conspiracy theories” any suggestions that Covid-19 didn’t have a natural origin. This is a question that remains unanswered today. Was there any purpose of that untruthful letter other than to intimidate the scientific debate at the pandemic’s start?

On Nov. 19, 2020, the Stanford Faculty Senate condemned my work as an adviser to President Trump, charging that I “promoted a view of COVID-19 that contradicts medical science.” Yet virtually every scientific point I made exactly matched those of Jay Bhattacharya and John Ioannidis, both Stanford professors of medicine, including the risk for children, spread from children, focused protection, postinfection immunity, masks, and the harm from school closures and lockdowns. The difference? I alone stood on the podium, speaking to the press and the public, serving my country next to a Republican president the Stanford faculty reviled.

Many American universities, particularly “elite” schools, now explicitly emphasize ideology even in the hard sciences. In a November report, the National Association of Scholars examined the proliferation of “diversity, equity and inclusion” language on the websites of Ivy League schools’ science, technology, engineering and mathematics departments. Stanford may now be the American university most hostile to free speech, with its recently exposed “Elimination of Harmful Language Initiative”—a list of approved and disapproved words that exceeds anything anticipated by George Orwell. After being publicly ridiculed, the school moved quickly to hide the list behind a university login.

Colleges and universities are essential to a free society. We entrust them with the responsibility to teach the next generation of leaders to think critically—a process that by its very essence requires consideration and comparison of opposing views. At their best, universities are centers for the free exchange of ideas and bastions of independent thought. At their worst they are centers of partisan indoctrination and ideological conformity. How do we return to a university that models the free exchange of ideas?

The problem can’t be solved by issuing more declarations on freedom. Like nearly all universities, Stanford has a longstanding institutional statement on academic freedom. Dating from 1974, it expounds: “Expression of the widest range of viewpoints should be encouraged free from institutional orthodoxy and from internal or external coercion.”

In theory, academics with unpopular views are protected by tenure. In practice, there’s a nuance to how dissidents are censored by the modern university. Regardless of tenure, one can be suspended without pay or marginalized to the point of invisibility. Formal censure can be decreed by the faculty senate. This kind of public condemnation by colleagues may seem an impotent expression of political hatred, but it serves to silence other university faculty members who are more easily frightened. I have received hundreds of emails from academics around the country urging me to keep speaking the truth. They say they are too afraid to do it themselves.

Public apologies from the failed expert class would partly restore trust and help prevent future abuses, but ultimately admission of error requires integrity. Realistically, then, the solution rests in people becoming courageous, particularly since bullies characteristically crumble when challenged. We need people of integrity in the academy to stand and be counted. That includes college presidents, some of whom disagree with the ideological rigidity of their faculties but are too cowed—or too comfortable—to say so.

We also need to hold universities accountable for failing to ensure academic freedom while raking in massive amounts of taxpayer money. Fifteen American research universities got over half a billion dollars from the National Institutes of Health in 2022. The dependence of the research enterprise, including the careers of virtually every academic scientist, on NIH money realistically limits their will to question, let alone criticize, the powerful agency and its leadership.

Finally, and perhaps most importantly, we need to keep teaching our own children, the next leaders of our country, to always remember what G.K. Chesterton wrote: “Right is right, even if nobody does it. Wrong is wrong, even if everybody is wrong about it.”

Dr. Atlas is a senior fellow in health policy at Stanford University’s Hoover Institution and a founding fellow at Hillsdale College’s Academy for Science and Freedom.

https://www.wsj.com/articles/when-will-academia-account-for-its-covid-failures-pandemic-lockdowns-stanford-ivy-league-elite-narrative-ideology-11672346923

Why 180 Life Sciences (ATNF) Stock Surged

 180 Life Sciences announced the closing of its previously announced registered direct offering priced at the market under Nasdaq rules with a single healthcare-focused U.S. institutional investor of 1,714,286 shares of the company’s common stock (or common stock equivalents in lieu thereof) and warrants to purchase up to 2,571,429 shares of common stock at a purchase price per share (and accompanying warrant) of $3.50.

These warrants have an exercise price of $3.50 per share, are initially exercisable beginning six months following the date of issuance and expire five years from the initial exercise date.

Proceeds: The gross proceeds from the offering are approximately $6 million. And the company plans to use the net proceeds from the offering for research and development expenses and general corporate purposes, including the preparation of a marketing authorization application for Dupuytren’s contracture in the UK and legal expenses.

Agent: A.G.P./Alliance Global Partners acted as the sole placement agent for the offering.

https://pulse2.com/why-the-180-life-sciences-atnf-stock-surged-over-50/

Triple immunotherapy combination as possible treatment for pancreatic cancer

 Researchers at The University of Texas MD Anderson Cancer Center have discovered a novel immunotherapy combination, targeting checkpoints in both T cells and myeloid suppressor cells, that successfully reprogrammed the tumor immune microenvironment (TIME) and significantly improved anti-tumor responses in preclinical models of pancreatic cancer.

In this study, published today in Nature Cancer, researchers used comprehensive immune profiling in mouse and human pancreatic cancers to systematically identify mechanisms of immunotherapy resistance and investigate potential therapeutic targets. They found that neutralizing several distinct immunosuppressive mechanisms of the TIME dramatically improved survival rates in laboratory models, pointing to a potential treatment option for this notoriously lethal and unresponsive cancer.

"This triple combination therapy led to an unprecedented curative response in our models," said corresponding author Ronald DePinho, M.D., professor of Cancer Biology. "The prevailing view has been that pancreatic cancer is impervious to immunotherapy, but this preclinical study shows that it can be vulnerable to the right combination therapy. Moreover, the presence of these targets in human pancreatic cancer specimens raises the exciting possibility that such therapeutic combinations could one day help our patients."

Pancreatic cancer is one of the leading causes of cancer death in the United States, partially because 80% of cases are diagnosed at an advanced stage. Pancreatic cancer is also considered to be "non-immunogenic," meaning it is unresponsive to commonly used anti-PD-1 and anti-CTLA-4 immune checkpoint inhibitors. This is due in part to the immunosuppressive conditions in the TIME, but the mechanisms behind this resistance are not fully understood.

The researchers used high-dimensional immune profiling and single-cell RNA sequencing to study how the TIME is affected by a variety of immunotherapies. They identified specific immune checkpoint proteins, 41BB and LAG, that were highly expressed in exhausted T cells.

In testing antibodies targeting these checkpoints, the researchers observed that models treated with a 41BB agonist and LAG3 antagonist in combination had slower tumor progression, higher levels of anti-tumor immunity indicators and significantly improved survival rates compared to treatment with either antibody alone or with other checkpoint inhibitors. Notably, these preclinical studies faithfully mirrored the human data in their lack of efficacy of anti-PD1 or anti-CTLA-4 therapy.

The researchers also confirmed these two therapeutic targets are present in human pancreatic cancer samples, with 81% and 93% of patients analyzed having T cells with 41BB and LAG3 expression, respectively.

Because this dual-therapy combination did not completely eliminate established tumors, the investigators also examined efforts to reprogram the TIME to further sensitize tumors to immunotherapy. At baseline, the TIME contained an abundance of myeloid-derived suppressor cells (MDSCs) expressing CXCR2, a protein associated with recruiting immunosuppressive cells. Inhibiting CXCR2 alone decreased MDSC migration and blocked tumor growth, but it was not curative. This prompted the investigators to consider a combination targeting 41BB, LAG3 and CXCR2.

It was this triple combination that resulted in complete tumor regression and improved overall survival in 90% of preclinical models. In a more stringent lab model that develops multiple spontaneously arising tumors with higher treatment resistance, the combination achieved complete tumor regression in over 20% of cases.

"These are encouraging results, especially considering the lack of effective immunotherapy options in pancreatic cancer," DePinho said. "By targeting multiple synergistic mechanisms that get in the way of the immune response, we can give T cells a fighting chance to attack these tumors. Of course, we still need to see how this combination translates into a safe and effective regimen in the clinic, and we invite other researchers to build upon these results. We are optimistic that pancreatic cancers, and hopefully other non-immunogenic cancers, can ultimately be rendered vulnerable to combination immunotherapy."

The authors point out that these particular immunotherapy agents currently are undergoing clinical trials as monotherapies, suggesting potential opportunities to rapidly translate this triple combination into clinical studies.

More information: Nature Cancer (2022). DOI: 10.1038/s43018-022-00500-z. dx.doi.org/10.1038/s43018-022-00500-z

https://medicalxpress.com/news/2022-12-triple-immunotherapy-combination-treatment-pancreatic.html

Autopsies show COVID-19 virus in brain, elsewhere in body

 An analysis of tissue samples from the autopsies of 44 people who died with COVID-19 shows that SAR-CoV-2 virus spread throughout the body—including into the brain—and that it lingered for almost eight months. The study was published in Nature.

Scientists from the National Institutes of Health (NIH) tested samples from autopsies that were performed from April 2020 to March 2021. They conducted extensive sampling of the nervous system, including the brain, in 11 of the patients.

RNA and viable virus in various organs

All of the patients died with COVID-19, and none were vaccinated. The blood plasma of 38 patients tested positive for SARS-CoV-2, three tested negative, and plasma was unavailable for the other 3.

Thirty percent of the patients were female, and the median age was 62.5 years. Twenty-seven patient (61.4%) had three or more comorbidities. The median interval from symptom onset to death was 18.5 days.

Analysis showed that SARS-CoV-2, as expected, primarily infected and damaged airway and lung tissue. But the researchers also found viral RNA in 84 distinct body locations and bodily fluids, and in one case they isolated viral RNA 230 days after a patient's symptoms began.

The researchers detected SARS-CoV-2 RNA and protein in the hypothalamus and cerebellum of one patient and in the spinal cord and basal ganglia of two other patients. But they found little damage to brain tissue, "despite substantial viral burden."

The investigators also isolated viable SARS-CoV-2 virus from diverse tissues in and outside the respiratory tract, including the brain, heart, lymph nodes, gastrointestinal tract, adrenal gland, and eye. They isolated virus from 25 of 55 specimens tested (45%).

The authors wrote, "We demonstrated virus replication in multiple non-respiratory sites during the first two weeks following symptom onset."

They add, "Our focus on short postmortem intervals, a comprehensive standardized approach to tissue collection, dissecting the brain before fixation, preserving tissue in RNA later, and flash freezing of fresh tissue allowed us to detect and quantify SARS-CoV-2 RNA levels with high sensitivity by [polymerase chain reaction] and [in situ hybridization], as well as isolate virus in cell culture from multiple non-respiratory tissues including the brain, which are notable differences compared to other studies."

Possible ramifications for long COVID

Senior study author Daniel Chertow, MD, MPH, said in an NIH news release that, prior to the work, "the thinking in the field was that SARS-CoV-2 was predominantly a respiratory virus."

Finding viral presence throughout the body—and sharing those findings with colleagues a year ago—helped scientists explore a relationship between widely infected bodily tissues and "long COVID," or symptoms that persist for weeks and months after infection.

Part of a Paxlovid RECOVER trial that is expected to begin in 2023 includes an extension of the autopsy work highlighted in the Nature study, according to coauthor Stephen Hewitt, MD, Ph.D., who serves on a steering committee for the RECOVER project. Autopsies in the RECOVER trial include people who both were vaccinated and infected with variants of concern—data that weren't available in yesterday's study.

"We're hoping to replicate the data on viral persistence and study the relationship with long COVID," Hewitt said. "Less than a year in, we have about 85 cases, and we are working to expand these efforts."

More information: Sydney R. Stein et al, SARS-CoV-2 infection and persistence in the human body and brain at autopsy, Nature (2022). DOI: 10.1038/s41586-022-05542-y

https://medicalxpress.com/news/2022-12-autopsies-covid-virus-brain-body.html

Ketamine found to increase brain noise

 An international team of researchers including Sofya Kulikova, Senior Research Fellow at the HSE University-Perm, found that ketamine, being an NMDA receptor inhibitor, increases the brain's background noise, causing higher entropy of incoming sensory signals and disrupting their transmission between the thalamus and the cortex. This finding may contribute to a better understanding of the causes of psychosis in schizophrenia. An article with the study's findings has been published in the European Journal of Neuroscience.

Schizophrenic spectrum disorders affect approximately one in 300 people worldwide. The most common manifestations of these disorders are perceptual disturbances such as hallucinations, delusions and psychoses.

A drug called ketamine can induce a mental state similar to psychosis in healthy individuals. Ketamine inhibits NMDA receptors involved in the transmission of excitatory signals in the brain. An imbalance of excitation and inhibition in the central nervous system can affect the accuracy of sensory perception.

Similar changes in the functioning of NMDA receptors are currently believed to be one of the causes of perception disorders in schizophrenia. However, it is still unclear how exactly this process occurs in the brain regions involved.

To find out, neuroscientists from France, Austria and Russia studied how the brains of laboratory rats on ketamine process sensory signals. The researchers examined beta and gamma oscillations occurring in response to sensory stimuli in the rodent brain's thalamo-cortical system , a neural network connecting the cerebral cortex with the thalamus responsible for the transmission of sensory information from the organs of perception to the brain.

Beta oscillations are brainwaves in the range of 15 to 30 Hz, and gamma waves are those in the range of 30 to 80 Hz. These frequencies are believed to be critical for encoding and integrating sensory information.

In the experiment, rats were implanted with microelectrodes to record the electrical activity in the thalamus and the somatosensory cortex , a region of the brain which is responsible for processing sensory information coming from the thalamus. The researchers stimulated the rats' whiskers (vibrissae) and recorded the brain's responses before and after ketamine administration.

A comparison of the two datasets revealed that ketamine increased the power of beta and gamma oscillations in the cortex and the thalamus even in the resting state before a stimulus was presented, while the amplitude of the beta/gamma oscillations in the 200–700 ms post-stimulus period was significantly lower at all recorded cortical and thalamic sites following ketamine administration.

The post-stimulation time lapse of 200–700 ms is long enough to encode, integrate and perceive the incoming sensory signal. The observed decrease in the power of sensory stimulus-induced oscillations can be associated with impaired perception.

Pre-stimulus beta and gamma frequencies on cortical and thalamic recordings are significantly higher under ketamine conditions (right) compared to saline (left) conditions . Credit:  Yi Qin et al. European Journal of Neuroscience

Analysis also revealed that by inhibiting NMDA receptors, ketamine administration added noise to gamma frequencies in the post-stimulation 200–700 ms period in one thalamic nucleus and in one layer of the somatosensory cortex. It can be assumed that this observed increase in noise, ie a reduction in the signal-to-noise ratio, also indicates the neurons' impaired ability to process incoming sensory signals.

These findings suggest that psychosis may be triggered by an increase in background noise impairing the function of thalamo-cortical neurons. This, in turn, could be caused by a malfunction of NMDA receptors affecting the balance of inhibition and excitation in the brain. The noise makes sensory signals less defined or pronounced. In addition, this may cause spontaneous outbursts of activity associated with a distorted perception of reality.

"The discovered alterations in thalamic and cortical electrical activity associated with ketamine-induced sensory information processing disorders could serve as biomarkers for testing antipsychotic drugs or predicting the course of disease in patients with psychotic spectrum disorders," says Sofya Kulikova.

More information: Yi Qin et al, The psychotomimetic ketamine disrupts the transfer of late sensory information in the corticothalamic network, European Journal of Neuroscience (2022). DOI: 10.1111/ejn.15845

Thomas J. Reilly, Ketamine: Linking NMDA receptor hypofunction, gamma oscillations and psychosis (commentary on Qin et al., 2022), European Journal of Neuroscience (2022). DOI: 10.1111/ejn.15872

https://medicalxpress.com/news/2022-12-ketamine-brain-noise.html