Now for the sitdown: Obama, Klain and Biden meet to discuss replacement, Kamala becomes Fredo

 By Monica Showalter

Like mafiosos, or the old gray men of the Kremlin trying to figure out how to get rid of Leonid Brezhnev or Konstantin Chernenko, Democrat power players have called in Joe Biden for a sitdown.

Dougie Kass, a hedge fund shark who leads Seabreeze Capital Partners of Palm Beach, Florida, reports the dirt:

 

 

He's echoed by MSNBC's Nicolle Wallace who says roughly the same thing. Kass, being a hedge fund guy, thrives on getting and acting on information before the herd stampedes, so he may well know what's going on. It wouldn't be surprising if Wallace, a consumate political operative and dirty trickster herself, might have some kind of inside track, too:

 

For those of us who have been wondering who pulls the puppet strings, now we have the answer -- Obama, and former chief of staff Ron Klain, who's got 'political operative' written all over him.

Since the meeting is supposedly going on around now, one can just imagine how that may go -- with Biden bitter and resentful at Godfather Obama's smooth manner, knack for words, two terms, and continued popularity, while Biden himself has none of those gifts. Now he's being told by Obama to step down because disaster is going to be what he gets if he doesn't. Klain the consigliere will be there to suggest muscle. Jill Biden, happy to play the role of Mrs. Wilson, and fond of the perks and travel she gets as first lady, will fight back hard. Joe will stare off into space, losing his train of thought.

And more laughable still, as Obama, and Klain discuss replacing Biden with Michigan Gov. Gretchen Whitmer, or California Gov. Gavin Newsom, no doubt offering up sweeteners -- business deals, immunity from prosecution for corruption -- and warn him Trump will throw him in jail if he wins, so he best save himself, outside the room, Vice President Kamala Harris will be fuming. Hadn't she served her role? Hadn't she done what she was told? They will treat her like Fredo as she pleads her case, thanks but no thanks. Perhaps she may be offered the California governor's slot in exchange for her cooperation. If she doesn't cooperate, she gets nothing. An offer she can't refuse. 

While Democrats are hardly sticklers for following their own laws and rules, there could be a few poison pills lying around:

 

 

After all, any Republican worth his or her salt would want to make sure the Democrats keep Biden at the top of the ticket.

Maybe they'll get even more mafia-like and arrange an 'accident.' But most likely, they will just let it get ugly and word will leak out to the press.

Wouldn't that be a pretty picture? Doesn't sound like a recipe for success for the Democrats as the walls come crashing down around them.

Let's get out the popcorn.

https://www.americanthinker.com/blog/2024/06/now_for_the_sitdown_obama_klain_and_biden_meet_to_discuss_replacement_kamala_becomes_fredo_report.html

'Is Semaglutide Anti-inflammatory?'

 The anti-obesity drug semaglutide is associated with significant reductions in the inflammatory marker high-sensitivity C-reactive protein (CRP), even in patients who do not lose substantial amounts of weight with the drug, according to data from the SELECT clinical trial.

The research, presented at the European Atherosclerosis Society 2024, involved over 17,600 patients with overweight or obesity and had established cardiovascular disease but not diabetes.

Those given semaglutide experienced a 38% reduction in high-sensitivity CRP levels compared with placebo regardless of baseline body mass index, statin use, cholesterol levels, and other measures.

"Weight loss was associated with greater high-sensitivity CRP reduction in both treatment groups," said study presenter Jorge Plutzky, MD, director of Preventive Cardiology at Brigham and Women's Hospital, Boston, Massachusetts, but "with increased high-sensitivity CRP reductions in those receiving semaglutide."

The drug also "significantly reduced high-sensitivity CRP early," he said, "prior to major weight loss and in those who did not lose significant amounts of weight." The reductions reached approximately 12% at 4 weeks and around 20% at 8 weeks, when the weight loss "was still quite modest," at 2% and 3% of body weight, respectively. Even among patients who achieved weight loss of less than 2% body weight, semaglutide was associated with a reduction in high-sensitivity CRP levels.

In the SELECT trial, semaglutide also resulted in a consistent reduction of around 20% vs placebo in major adverse cardiovascular events such as cardiovascular mortality, nonfatal myocardial infarction, or nonfatal stroke.

But Naveed Sattar, MD, PhD, professor of cardiometabolic medicine at the University of Glasgow, Scotland, United Kingdom, said in an interview that body weight "is probably the major driver" of CRP levels in the population, accounting for between 20% and 30% of the variation.

Sattar, who was not involved in the study, said that because drugs like semaglutide lower weight but also have anti-inflammatory effects, the question becomes: "Could the anti-inflammatory effects be part of the mechanisms by which these drugs affect the risk of major adverse cardiovascular events?"

Reducing Cardiovascular Events

The current analysis, however, cannot answer the question, he said. "All it tells us is about associations."

"What we do know is semaglutide, predominantly by lowering weight, is lowering CRP levels and equally, we know that when you lose weight, you improve blood pressure, you improve lipids, and you reduce the risk of diabetes," he said.

Sattar also took issue with the researchers' conclusion that the high-sensitivity CRP reductions seen in SELECT occurred prior to major weight loss because the "pattern of CRP reduction and weight reduction is almost identical."

Sattar also pointed out in a recent editorial that the drug appears to have a direct effect on blood vessels and the heart, which may lead to improvements in systemic inflammation. Consequently, he said, any assertion that semaglutide is genuinely anti-inflammatory is, at this stage, "speculation."

Plutzky said that "systemic, chronic inflammation is implicated as a potential mechanism and therapeutic target in atherosclerosis and major adverse cardiovascular events, as well as obesity," and high-sensitivity CRP levels are an "established biomarker of inflammation and have been shown to predict cardiovascular risk."

However, the relationship between high-sensitivity CRP, responses to glucagon-like peptide 1 receptor agonists like semaglutide, and cardiovascular outcomes in obesity "remains incompletely understood," said Plutzky.

https://www.medscape.com/viewarticle/semaglutide-anti-inflammatory-2024a1000c4l

Revised Criteria for Alzheimer's Diagnosis, Staging Released

 A work group convened by the Alzheimer's Association has released revised biology-based criteria for the diagnosis and staging of Alzheimer's disease (AD), including a new biomarker classification system that incorporates fluid and imaging biomarkers as well as an updated disease staging system. 

"Plasma markers are here now, and it's very important to incorporate them into the criteria for diagnosis," senior author Maria C. Carrillo, PhD, Alzheimer's Association chief science officer and medical affairs lead, told Medscape Medical News. 

The revised criteria are the first updates since 2018.

"Defining diseases biologically, rather than based on syndromic presentation, has long been standard in many areas of medicine — including cancer, heart disease and diabetes — and is becoming a unifying concept common to all neurodegenerative diseases," lead author Clifford Jack, Jr, MD, with Mayo Clinic, Rochester, Minnesota, said in a news release from the Alzheimer's Association. 

"These updates to the diagnostic criteria are needed now because we know more about the underlying biology of Alzheimer's and we are able to measure those changes," Jack added. 

The 2024 revised criteria for diagnosis and staging of AD were published online on June 28 in Alzheimer's & Dementia. 

Core Biomarkers Defined

The revised criteria define AD as a biologic process that begins with the appearance of AD neuropathologic change (ADNPC) in the absence of symptoms. Progression of the neuropathologic burden leads to the later appearance and progression of clinical symptoms.

The work group organized AD biomarkers into three broad categories: (1) core biomarkers of ADNPC, (2) nonspecific biomarkers that are important in AD but are also involved in other brain diseases, and (3) biomarkers of diseases or conditions that commonly coexist with AD.

Core Alzheimer's biomarkers are subdivided into Core 1 and Core 2. 

Core 1 biomarkers become abnormal early in the disease course and directly measure either amyloid plaques or phosphorylated tau (p-tau). They include amyloid PET; cerebrospinal fluid (CSF) amyloid beta 42/40 ratio, CSF p-tau181/amyloid beta 42 ratio, and CSF total (t)-tau/amyloid beta 42 ratio; and "accurate" plasma biomarkers, such as p-tau217. 

"An abnormal Core 1 biomarker result is sufficient to establish a diagnosis of AD and to inform clinical decision making [sic] throughout the disease continuum," the work group wrote. 

Core 2 biomarkers become abnormal later in the disease process and are more closely linked with the onset of symptoms. Core 2 biomarkers include tau PET and certain soluble tau fragments associated with tau proteinopathy (eg, MTBR-tau243) but also pT205 and nonphosphorylated mid-region tau fragments. 

Core 2 biomarkers, when combined with Core 1, may be used to stage biologic disease severity; abnormal Core 2 biomarkers "increase confidence that AD is contributing to symptoms," the work group noted. 

The revised criteria give clinicians "the flexibility to use plasma or PET scans or CSF," Carrillo told Medscape Medical News. "They will have several tools that they can choose from and offer this variety of tools to their patients. We need different tools for different individuals. There will be differences in coverage and access to these diagnostics." 

The revised criteria also include an integrated biologic and clinical staging scheme that acknowledges the fact that common co-pathologies, cognitive reserve, and resistance may modify relationships between clinical and biologic AD stages. 

Formal Guidelines to Come 

The work group noted that currently, the clinical use of AD biomarkers is intended for the evaluation of symptomatic patients, not cognitively unimpaired individuals.

Disease-targeted therapies have not yet been approved for cognitively unimpaired individuals. For this reason, the work group currently recommends against diagnostic testing in cognitively unimpaired individuals outside the context of observational or therapeutic research studies. 

This recommendation would change in the future if disease-targeted therapies that are currently being evaluated in trials demonstrate a benefit in preventing cognitive decline and are approved for use in preclinical AD, they wrote. 

They emphasize that the revised criteria are not intended to provide step-by-step clinical practice guidelines for clinicians. Rather, they provide general principles to inform diagnosis and staging of AD that reflect current science.

"This is just the beginning," said Carrillo. "This is a gathering of the evidence to date and putting it in one place so we can have a consensus and actually a way to test it and make it better as we add new science."

This also serves as a "springboard" for the Alzheimer's Association to create formal clinical guidelines. "That will come, hopefully, over the next 12 months. We'll be working on it, and we hope to have that in 2025," Carrillo said. 

The revised criteria also emphasize the role of the clinician. 

"The biologically based diagnosis of Alzheimer's disease is meant to assist, rather than supplant, the clinical evaluation of individuals with cognitive impairment," the work group wrote in a related commentary published online on June 28 in Nature Medicine. 

Recent diagnostics and therapeutic developments "herald a virtuous cycle in which improvements in diagnostic methods enable more sophisticated treatment approaches, which in turn steer advances in diagnostic methods," they continued. "An unchanging principle, however, is that effective treatment will always rely on the ability to diagnose and stage the biology driving the disease process."

Funding for this research was provided by the National Institutes of Health, Alexander family professorship, GHR Foundation, Alzheimer's Association, Veterans Administration, Life Molecular Imaging, Michael J. Fox Foundation for Parkinson's Research, Avid Radiopharmaceuticals, Eli Lilly, Gates Foundation, Biogen, C2N Diagnostics, Eisai, Fujirebio, GE Healthcare, Roche, National Institute on Aging, Roche/Genentech, BrightFocus Foundation, Hoffmann-La Roche, Novo Nordisk, Toyama, National MS Society, Alzheimer Drug Discovery Foundation, and others. A complete list of donors and disclosures is included in the original article. 

https://www.medscape.com/viewarticle/revised-criteria-alzheimers-diagnosis-staging-released-2024a1000c4g

'It's a mess': Biden turns to family on his path forward after his disastrous debate

 President Joe Biden is expected to discuss the future of his re-election campaign with family on Sunday, following a nationally televised debate Thursday that left many fellow Democrats worried about his ability to beat former President Donald Trump in November, according to five people familiar with the matter.

Biden’s trip to Camp David was planned before Thursday’s debate. He and first lady Jill Biden are scheduled to join their children and grandchildren there late Saturday.

So far, the party’s top leaders have offered public support for Biden, including in tweets posted by former presidents Barack Obama and Bill Clinton. Senior congressional Democrats, including Reps. Hakeem Jeffries of New York, Jim Clyburn of South Carolina and Nancy Pelosi of California, have privately expressed concerns about his viability, said two sources apprised of those discussions, even as they all publicly back the president.

One Democratic House member who believes Biden should drop out of the race — but has yet to call for that publicly — told NBC News that three colleagues expressed the same sentiment to him during votes on the House floor Friday.

At the same time, there is an understanding among top Democrats that Biden should be given space to determine next steps. They believe only the president, in consultation with his family, can decide whether to move forward or to end his campaign early — and that he won’t respond well to being pushed.

“The decision-makers are two people — it’s the president and his wife,” one of the sources familiar with the discussions said, adding: “Anyone who doesn’t understand how deeply personal and familial this decision will be isn’t knowledgeable about the situation.”

This account of a president and his party in crisis just a little more than four months before an election they say will determine the fate of democracy is drawn from interviews with more than a dozen Democratic officials, operatives, aides and donors. All of them spoke on the condition of anonymity in order to describe matters as sensitive as whether a sitting president might give up his re-election bid and how he could be replaced on the ballot.

Despite delivering a rousing speech at a rally in North Carolina on Friday that calmed some of his allies, Biden was described by one person familiar with his mood as humiliated, devoid of confidence and painfully aware that the physical images of him at the debate — eyes staring into the distance, mouth agape — will live beyond his presidency, along with a performance that at times was meandering, incoherent and difficult to hear.

“It’s a mess,” this person said.

Another person familiar with the dynamics said Biden will ultimately listen to only one adviser.

“The only person who has ultimate influence with him is the first lady,” this person said. “If she decides there should be a change of course, there will be a change of course.”

Anita Dunn, one of Biden’s handful of closest advisers, said on MSNBC’s “The Weekend” Saturday that Biden has not discussed dropping out of the race with aides and that internal talks have focused on moving forward.

“We had a bad debate,” Dunn said. “What do we do next? You know, the president, above all, is focused on what do we do next? What do I need to go do?”

0 seconds of 11 minutes, 59 secondsVolume 90%

 

How the Biden campaign moves forward after a lackluster debate performance 

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These private discussions among Biden, his family members and his top advisers are being held against the backdrop of a reckoning for Democrats who were shocked both by Biden’s appearance and the frequency with which his train of thought appeared to veer off track.

His campaign held a conference call Saturday with members of the Democratic National Committee, which a Biden campaign official described as an effort to reassure party officials and demonstrate that his team is communicating with its allies.

“We’re driving this,” the official said.

House leaders have not wavered publicly, and their aides denied that they are expressing doubts behind closed doors.

“Speaker Pelosi has full confidence in President Biden and looks forward to attending his inauguration on January 20, 2025,” Ian Krager, a spokesman for the former House speaker said. “Any suggestion that she has engaged in a different course of action is simply not true.”

Christie Stephenson, a spokeswoman for Jeffries, the House minority leader, said her boss has “repeatedly made clear publicly and privately that he supports President Joe Biden and the Democratic ticket from top to bottom.”

Clyburn’s office did not reply to a request for comment, but he told reporters Friday that he is still with Biden.

Biden’s top aides and advisers have told his staff to stay the course in meetings and discussions. Their message, according to one senior administration official: “We’ll weather the storm, just like we always have.”

Sources have described three buckets of Democrats: those who will defend Biden under any circumstances, those who are ready to dump him, and those who are waiting to see what he does — and what his poll numbers look like in the coming days and weeks — before passing judgment. It’s the third bucket that Democratic insiders are monitoring closely.

“Democrats need to take a big breath and look at that polling, look at swing voters,” said one state Democratic Party chair. “Until I see something differently, he’s the person that’s put this coalition together, he’s the person that has the record, he’s the person that beat Donald Trump. Until I see something differently, he’s still the best person to beat Donald Trump.”

The Biden campaign declined to comment for this piece, instead pointing to a memo Saturday from campaign chair Jen O’Malley Dillon that made the case that Biden can still win, pointing to the more than $27 million they raised between debate day and Friday evening.

Notably, however, O’Malley Dillon nodded to the possibility that there might be some tough polling ahead — but said the blame will rest with the media: “If we do see changes in polling in the coming weeks, it will not be the first time that overblown media narratives have driven temporary dips in the polls.”

The discussions among some Democrats include weighing what the party’s best path to defeating Trump might be — sticking with an 81-year-old incumbent who could have another moment like Thursday night at any time between now and Election Day, or going with a different candidate whose path to nomination at the party’s convention next month could be a messy process.

Biden insisted Friday that he will remain the party’s standard-bearer in November, telling a crowd at his rally in Virginia, “I would not be running again if I didn’t believe with all my heart and soul I can do this job.”

The president has spent much of the past 48 hours attending fundraising events with some of the very Democrats most concerned about the impact of his debate performance.

He addressed it head-on at one event Saturday.

“I understand the concern about the debate — I get it,” he added. “I didn’t have a great night.”

Party elites will urge him to exit the race only if they determine that he is “not viable and negatively impacting the House and Senate races,” said one big-time donor who is close to both Obama and Biden.

Inherent in the wait-and-see approach is an acknowledgment that there is no clear replacement for Biden and that his departure could touch off a bloody eleventh-hour intraparty battle that might allow Trump to cruise to victory.

There’s also no feasible way to force him from his perch. All but a handful of the delegates to the Democratic convention were elected on their pledge to nominate him at the party’s convention in August. If he chooses to stand for that nomination, party insiders say, he will get it.

Moreover, according to a senior Democratic official, the party leadership would have much more control over choosing a replacement if Biden were to drop out after receiving the nomination than if he did so beforehand. Once a candidate is officially nominated, there is a process for the Democratic National Committee members to choose a successor. Biden is the dominant force at the DNC, and his preference for a successor would surely carry sway.

If Biden were to exit before that, his delegates might do what he asked of them — but they wouldn’t be bound in the same way they are now. In that scenario, the delegates could nominate anyone, and there could be a political brawl at the convention.

“We need to have as much discipline as emotion,” the senior Democratic official said. “It’s not politically smart for Biden to step down.”

https://www.nbcnews.com/politics/2024-election/biden-family-path-forward-disastrous-debate-mess-rcna159591

New Drugs Turned Down by EU Safety Assessor

 The European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has given negative opinions for two drugs intended to treat amyotrophic lateral sclerosis (ALS) and age-related macular degeneration (AMD). It also recommended nonrenewal of a conditional authorization for a Duchenne muscular dystrophy medication.

ALS Medicine Not Recommended 

At its June 2024 meeting, the CHMP said that it recommended refusal of marketing authorization for masitinib (AB Science), a medicine intended to treat ALS. Its active substance, masitinib mesylate, is a protein kinase inhibitor that blocks enzymes involved in various immune-mediated inflammatory processes. The expectation was that this would reduce inflammation and protect nerve cells from damage, thereby slowing the worsening of ALS symptoms.

Masitinib, which was given orphan drug designation in 2016, is an oral tablet intended to be used in combination with riluzole, a drug indicated to extend life or time to mechanical ventilation in patients with ALS but which has no therapeutic effect on motor function, lung function, fasciculations, muscle strength, or motor symptoms. 

AB Science presented evidence from a trial of 394 adults with ALS treated with masitinib or placebo, both in combination with riluzole, twice daily for 48 weeks. The main measure of effectiveness was the change over 48 weeks in an ALS-specific quality-of-life score. However, the CHMP said, drug benefits could not be convincingly demonstrated. The trial found no difference between the active drug and placebo in the main measure of effectiveness and had several methodological issues that made the data unreliable.

The European Medicines Agency's opinion therefore was that the benefits of masitinib did not outweigh its risks. There are no consequences for patients in ongoing clinical trials with the drug, and the company may ask for reexamination of the opinion within 15 days.

AMD Drug Not Recommended 

The CHMP also did not recommend marketing authorization for Syfovre (pegcetacoplan; Apellis Europe B.V.), a drug intended to treat geographic atrophy secondary to AMD. Geographic atrophy is an advanced form of dry AMD in which lesions form in the retina and macula, causing large, well-demarcated sections of the retina to stop functioning, leading to irreversible loss of vision.

With geographic atrophy, the complement system is overactive, leading to inflammation and cell death in the retina. The drug's active substance is pegcetacoplan, which is injected into the eye as a solution. It works by blocking the C3 protein of the complement system, thus preventing complement activation and slowing the growth of atrophic lesions.

The company presented results from two main trials involving 1258 adults with AMD and geographic atrophy. Pegcetacoplan injections were compared with sham procedures, and any changes in lesion size were examined 12 months later.

The CHMP said that although the results showed that pegcetacoplan did slow the growth of lesions, this did not lead to clinically meaningful benefits for patients. Given the risks of regular injections into the eye, the CHMP said that a positive balance of benefits and risks could not be established, and it recommended refusing marketing authorization.

Again, there are no consequences for patients taking the drug as part of a clinical trial, and the company may ask for reexamination of the opinion within 15 days of receiving it.

Conditional Authorization for Translarna Not Recommended for Renewal

The CHMP also recommended not renewing the conditional marketing authorization for Translarna (ataluren; PTC Therapeutics), a medicine for treating some patients with Duchenne muscular dystrophy.

Translarna is used in patients whose disease is caused by a nonsense mutation in the dystrophin gene and who are still able to walk. An initial negative opinion on the renewal of its marketing authorization was given last September and was confirmed in January this year, following a reexamination requested by the company. The CHMP said that following reevaluation of the drug's benefits and risks, both rounds of assessment had concluded that Translarna's effectiveness had not been confirmed.

Last month, the European Commission had asked the CHMP to further consider whether new data from a scientific advisory group on neurology convened in March this year affected its conclusions on the medicine's benefit-risk balance. Further publications were reviewed, along with input from parents or caregivers of boys affected by Duchenne muscular dystrophy, patient organizations, healthcare professional organizations, and treating doctors, as well as reports on individual patients treated with Translarna.

The CHMP concluded, after a thorough assessment of the totality of the data, that despite the high unmet medical need for an effective treatment for patients with this rare disease, there was still insufficient evidence to confirm Translarna's effectiveness. Therefore, the benefit-risk balance was negative and the CHMP recommended not renewing its marketing authorization in the EU.

This opinion will now be forwarded to the European Commission for a final legally binding decision applicable in all EU member states.

https://www.medscape.com/viewarticle/eu-safety-assessor-turned-down-new-drugs-2024a1000c44