Day: 12/24/2021

New-onset diabetes provides ‘window of opportunity’ for early pancreatic cancer detection

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Pancreatic cancer often is called the silent killer.

Most people with early disease show no symptoms. Consequently, 80% of cases are diagnosed in late stages when surgery is no longer possible and other treatment options are limited. Fewer than 10% of patients survive 5 years after diagnosis.

Efforts to accelerate research into the link between new-onset diabetes and pancreatic cancer are critical, according to Brian M. Wolpin, MD, MPH. “The idea that there may be people out there who have some signal [to show] the cancer may be present but we aren’t identifying them in a way that [allows us] to diagnosis the cancer early is upsetting,” Wolpin said.
Efforts to accelerate research into the link between new-onset diabetes and pancreatic cancer are critical, according to Brian M. Wolpin, MD, MPH. “The idea that there may be people out there who have some signal [to show] the cancer may be present but we aren’t identifying them in a way that [allows us] to diagnosis the cancer early is upsetting,” Wolpin said.

Source: Dana-Farber Cancer Institute.

Early detection has been heralded as the holy grail to reduce mortality of pancreatic cancer, set to become the second leading cause of cancer death in the United States by 2040.

A deeper understanding of the link between new-onset diabetes and pancreatic cancer may play a key role in that effort.

One study showed individuals with new-onset diabetes are up to eight times more likely than the general population to develop pancreatic cancer. Another suggested the increased risk for pancreatic cancer among people with new-onset diabetes is comparable to the elevated risk for lung cancer observed among those who smoked a pack of cigarettes per day for 2 decades.

A history of pancreatitis also may be a key indicator, with a study showing patients with diabetes that developed secondary to a pancreatitis attack had a seven times higher risk for pancreatic cancer than individuals with type 2 diabetes.

Two major research collaborations are underway to explore the link between pancreatic cancer and new-onset diabetes.

The NCI is leading a multidisciplinary effort to determine which individuals newly diagnosed with diabetes are at elevated risk for pancreatic cancer. A second study will examine whether imaging at the time of new-onset diabetes results in earlier pancreatic cancer detection.

This potentially practice-informing research is crucial to improve the typically poor prognosis for patients with this aggressive malignancy, according to Brian M. Wolpin, MD, MPH, director of the gastrointestinal cancer center and Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute.

“The idea that there may be people out there who have some signal [to show] the cancer may be present but we aren’t identifying them in a way that [allows us] to diagnosis the cancer early is upsetting,” Wolpin told HemOnc Today. “It’s frustrating, but it’s also the challenge we want to tackle, so that we find pancreatic cancer earlier when it can be cured.”

HemOnc Today spoke with oncologists and endocrinologists about the link between new-onset diabetes and pancreatic cancer, the actionable insights that may emerge from current research efforts, the biologic factors that may predict which patients with new-onset diabetes may be most at risk for pancreatic cancer, and the need for increased awareness of this association across medical specialties.

‘Bidirectional relationship’

It is difficult — and often impossible — to determine the exact temporal or causal relationship between diabetes and pancreatic cancer, according to Max Petrov, MD, PhD, MPH, professor of pancreatology at The University of Auckland School of Medicine in New Zealand and founder of the COSMOS group, which focuses on translational clinical and epidemiological research in pancreatic diseases.

Max Petrov, MD, PhD, MPH
Max Petrov

“It is possible that, in some patients, diabetes leads to development of pancreatic cancer. It is also possible pancreatic cancer leads to development of diabetes,” Petrov told HemOnc Today.

Diabetes duration — specifically new-onset diabetes, meaning diagnosed within the prior 3 years, as opposed to long-standing diabetes — can be used as a guide, he added.

“The shorter the time since diabetes onset, the higher the chance the diabetes the primary care provider or endocrinologist sees is the first manifestation of cancer that has not been diagnosed,” Petrov said.

In these cases, the mechanism is “fairly straightforward,” Petrov said.

“It is the so-called paraneoplastic syndrome,” he said. “As a part of this syndrome, endocrine dysfunction in the beta cells develops. The key thing to note is this is a nonspecific syndrome, which will have implications for screening.”

Mark O. Goodarzi, MD, PhD, FACP, director of the division of endocrinology, diabetes and metabolism and Eris M. Field chair in diabetes research at Cedars-Sinai, suggested a “bidirectional relationship” is at play.

“Factors such as inflammation or altered immune markers might play a role,” he said. “As far as longstanding diabetes, obesity may be a key contributor. People who are obese and have diabetes often have high insulin levels, and insulin can stimulate cell division. Over time, high levels of insulin could promote tumor formation. This is not proven, but it is a theory.

“The concept with new-onset diabetes is that the pancreatic cancer cells themselves might be producing some factor that causes diabetes,” Goodarzi added.

An ‘astounding’ finding

Suresh T. Chari, MD, professor in the department of gastroenterology, hepatology and nutrition in the division of internal medicine at The University of Texas MD Anderson Cancer Center, has examined the link between new-onset diabetes and pancreatic cancer since the late 1990s.

Suresh T. Chari, MD
Suresh T. Chari

During a fellowship in gastroenterology at Mayo Clinic, Chari and colleagues assessed a population-based cohort of 2,122 residents of Rochester, Minnesota, aged 50 years or older who met criteria for diabetes between 1950 and 1994. They identified those who developed pancreatic cancer within 3 years of meeting diabetes criteria, then compared incidence in that cohort with expected rates from a separate SEER registry.

Their results appeared in Gastroenterology in 2005.

“An astounding 0.85% [of the Rochester cohort] had pancreatic cancer,” Chari told HemOnc Today. “That is a six- to eightfold higher risk compared with the general population.”

For context, the observed rate was comparable to yields of colorectal cancer by colonoscopy (0.7%), lung cancer by CT scan (0.65%) and breast cancer by mammography, Chari added.

Chari tried for years to highlight the importance of this observation. The medical community finally began to take notice within the last decade.

Pancreatic Cancer Action Network (PanCAN) — a U.S.-based charity that provides research funding, as well as patient support and community outreach — formed the Deadliest Cancers Coalition in 2008 to address policy issues related to the most lethal cancers.

In 2012, Congress passed the Recalcitrant Cancer Research Act, which required NCI to develop a strategic plan to advance pancreatic cancer research. A committee met for the first time in 2014.

“Among the concepts presented was that diabetes is a marker for pancreatic cancer,” Chari said. “The director caught onto it and, when [a subsequent] white paper came out on directions for pancreatic cancer research, the No. 1 research priority was to understand the link between diabetes and pancreatic cancer.”

NCI statistics now show one in four people diagnosed with pancreatic cancer had a prior diabetes diagnosis, and about one in 100 people diagnosed with new-onset diabetes will be diagnosed with pancreatic cancer within 3 years.

Kenner and colleagues published a review earlier this year in Pancreas that further quantified the association.

The authors, who aimed to explore the potential role of artificial intelligence in early detection of pancreatic cancer, divided study participants into six risk groups.

The group at highest risk, which included individuals with new-onset diabetes, had a six- to 10-fold higher risk (0.67% to 1% absolute risk) for pancreatic cancer — comparable to the elevated risk for lung cancer observed among people with a 20 pack-year smoking history.

However — unlike for colorectal, lung or breast cancer — there is no widely used screening modality or protocol for pancreatic cancer. Testing every patient with new-onset diabetes is neither logistically nor financially feasible.

Mark O. Goodarzi, MD, PhD, FACP
Mark O. Goodarzi

“It is certainly not going to be cost-effective to send every patient with new-onset diabetes for imaging for pancreatic cancer,” Goodarzi said. “More than 95% of them simply will have type 2 diabetes.”

In addition — unless a person has undergone regular blood tests — it is difficult to pinpoint when they became diabetic and, subsequently, identify those most likely to present short term with pancreatic cancer.

Ziding Feng, PhD
Ziding Feng

“Patients don’t have blood tests frequently enough — even at [practices] where their health providers actually pay for it,” Ziding Feng, PhD, professor in the public health sciences division and co-leader of the biostatistics program at Fred Hutchinson Cancer Research Center, told HemOnc Today.

“We want to be able to see [results from] the past 18 months to see if they had at least one normal blood sugar,” Feng added. “That requires at least two annual tests. If we don’t have that, we don’t know if the diabetes is new or old.”

Identifying those most at risk

The challenges that make pancreatic cancer detection and treatment so difficult are a daily reality for many oncologists.

“Based on the numbers, when 80% of my patients walk through the door for the first time, I know that we are highly unlikely to cure their cancer,” Wolpin said.

However, Wolpin is encouraged by advances in early detection over the past half-dozen years. Among them:

  • understanding the inherited basis of pancreatic cancer, including uncovering genetic mutations that identify high-risk individuals for screening and that now indicate a role for genetic testing in all patients who present with pancreatic cancer;
  • increased knowledge of cystic lesions of the pancreas, important precursors to invasive cancer that are more detectable via imaging than other lesions;
  • advances in blood-based cancer detection assays; and
  • improved understanding and awareness of the relationship of pancreatic cancer with hyperglycemia.

Each advance provides a potential strategy to detect pancreatic cancer — and identify which individuals with new-onset diabetes may be at greatest risk.

“If there is a test that can detect cancer before anything else is visible, the subset of patients with new diabetes or new prediabetes could undergo that test,” Chari said. “Now you have a dual approach to finding someone who is at risk.”

Lack of useful biomarkers, however, remains a challenge.

“We not only need blood collected from patients with new-onset diabetes and pancreatic cancer, we also need blood from patients with new-onset diabetes without pancreatic cancer at the time of diabetes onset,” Feng said. “That is the right specimen, but you cannot find such a specimen anywhere.”

Considerable investment, potentially big dividends

Oncologists and endocrinologists are optimistic that two major research initiatives may yield new insights, as well as the biological specimens necessary to understand the diabetes-pancreatic cancer link in a way that could lead to more effective detection strategies and, thus, improved patient outcomes.

The NCI-led New Onset Diabetes Study (NOD) — launched in 2018 — is designed to enroll 10,000 people aged 50 to 85 years across the United States newly diagnosed with diabetes or hyperglycemia.

Researchers will follow study participants for 3 years and calculate pancreatic cancer incidence rates.

The regular blood and tissue samples they collect during that “critical time window” could capture important insights, said Feng, the NOD study’s principal investigator.

Researchers hope the information they glean will help develop a blood test that can determine which individuals with new-onset diabetes are most likely to develop pancreatic cancer and could benefit from additional imaging or further workup.

“If we could leverage that new-onset diabetes to pick up these patients well before the tumors have grown to a large size, it would make a huge difference in their survival,” Goodarzi said. “That is why the NIH is investing so much in this NOD study. We will have blood samples before the cancer manifests. It will be a great resource to go back to and look for biomarkers in the patients who did develop cancer.”

The target completion date for the NOD study is December 2025. However, enrollment has been slower than expected, standing at about 1,500 patients — or 15% of the target.

PanCAN announced a randomized study — the Early Detection Initiative for Pancreatic Cancer (EDI) — this summer.

The $25 million initiative will enroll 12,500 participants based on first-time elevation in fasting blood glucose or HbA1c.

Researchers will randomly assign participants to an observational group or an intervention group. Those in the intervention group will have enriching new-onset diabetes for pancreatic cancer (ENDPAC) scores calculated based on age, body weight and glucose/HbA1c values. Those with ENDPAC scores greater than 0 will undergo abdominal imaging.

Participants also will provide blood samples at up to five time points.

Researchers hope to determine whether imaging at the time of new-onset diabetes helps detect pancreatic cancer earlier. Study participants’ blood samples will be added to an NCI collection so they can be analyzed for possible pancreatic cancer biomarkers, which could lead to development of a screening modality that allows for detection of pancreatic cancer when it is amenable to surgery.

The target completion date is 2030.

“These two big investments will pay dividends,” Feng said. “Of course, the study teams have to deliver.”

‘Awareness is critical’

Results of the NOD and EDI studies eventually may lead to earlier detection of some pancreatic cancer cases, potentially altering the treatment landscape.

Feng said he is optimistic technology also could play a “game-changing” role in detection.

However, until trial data yield new insights or technologic breakthroughs become mainstream, experts said physicians and researchers who treat pancreatic cancer must continue to advocate for their patients and the research that could help them.

It is essential to educate providers in a range of medical specialties — including primary care, hospital medicine and endocrinology — about the link between new-onset diabetes and pancreatic cancer, according to experts with whom HemOnc Today spoke.

“Don’t delay diagnosis of diabetes because you’ll lose that window of opportunity to intervene,” Chari said.

Health changes around the time of diabetes diagnosis may be indicative of an eventual pancreatic cancer diagnosis. If a patient presents with diabetes, physicians should run through a checklist, Wolpin said.

“Does the elevation in glucose seem much more rapid than [for the] average patient or is the blood sugar particularly difficult to control? Is the patient losing weight in a way that seems abnormal and isn’t due to a lifestyle change?” Wolpin said. “And what is their age? Are they fine and then, all of a sudden, at age 72 they get diabetes and it’s not clear why?

“These are all warning signs that physicians should be aware of,” Wolpin added. “These are not biomarkers in terms of advanced tests, but they all go together to help raise suspicion of whether [an underlying] pancreatic cancer is present.”

Family history of pancreatic cancer is a potential warning sign, Goodarzi said. So is lack of relatives with diabetes, given type 2 diabetes “almost always” runs in a family, he added. Other considerations include gastrointestinal symptoms, loss of appetite or jaundice.

“The ENDPAC model includes factors such as age of diabetes diagnosis, weight changes and blood glucose changes over 1 year,” Goodarzi said. “The sensitivity of this model seems to be around 55%. Down the road, we will need a combination of clinical features and biomarkers, but we don’t have that yet.

“For now, it is the ‘art of medicine,’” Goodarzi added. “If a patient’s clinical presentation of diabetes makes you think twice, and it does not look like garden-variety diabetes, you may want to screen for pancreatic cancer.”

Petrov, however, cautioned that weight loss and increases in blood glucose are “nonspecific symptoms” and it remains impossible to determine with certainty which patients will develop pancreatic cancer or any other malignancy.

However, he highlighted a study his COSMOS group conducted that suggested history of pancreatitis could be a key indicator.

His group performed a large, population-based study of 140,000 people in New Zealand with type 2 diabetes. They aimed to determine if a specific subpopulation may be at higher risk for pancreatic cancer.

The results, which included up to 18 years of follow-up, appeared in 2020 in Diabetes Care.

“What we found was quite spectacular,” Petrov said. “Patients who had diabetes that developed secondary to an attack of pancreatitis had a seven times higher risk for pancreatic cancer than people with type 2 diabetes. In absolute numbers, the frequency of pancreatic cancer increased from 0.7% [in the overall cohort] to 3.1% for those with diabetes and a history of pancreatitis. This didn’t require sophisticated blood tests or costly imaging — just asking about history. It is conceivable that taking into account history of pancreatitis will markedly enrich cohorts of people with new-onset diabetes for pancreatic cancer and ultimately enable cost-effective and achievement-appropriate screening for this disease.”

The results also suggested it is important to consider the temporal relationship between pancreatitis and diabetes, Petrov said.

“When new-onset diabetes after pancreatitis was compared with diabetes that developed before pancreatitis, the former was associated with more than two times higher risk for pancreatic cancer,” he said. “This is important not only from the perspective of screening, but also from the perspective of trying to figure out the intricate mechanisms underlying the link between diabetes and pancreatic cancer. Our findings indicate that new-onset diabetes in itself is a relatively minor, although certainly non-negligible, risk factor for pancreatic cancer. New-onset diabetes plays a role as a nonspecific amplifier of major pancreas-specific risk factors such as pancreatitis.”

Aside from physical predictors, awareness among the general population also would be valuable, Wolpin said.

A deeper understanding of smoking’s role in lung cancer led to large-scale trials that resulted in the development of national guidelines for screening high-risk populations. Increased awareness of the diabetes-pancreatic cancer relationship could be equally transformational, Wolpin said.

“We need to mimic what the scientific community did for smoking and lung cancer,” Wolpin said. “Ultimately, trials were conducted that showed low-dose CT scans could detect the disease early, and now this form of screening is considered a standard of quality care.

“If no one realizes the diabetes-pancreatic cancer link is present, they will be less likely to participate in studies like NO and EDI, which are greatly needed,” Wolpin added. “Awareness is a critical part of making a difference.”

FDA approves inclisiran for LDL lowering

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Novartis announced the FDA approved inclisiran, its small-interfering RNA therapy for LDL lowering.

After an initial dose and one at 3 months, inclisiran (Leqvio) is administered twice per year as a subcutaneous injection, according to a press release issued by the company.

Approved FDA_Shutterstock

The drug was approved as an adjunct to diet and maximally tolerated statin therapy for adults with clinical atherosclerotic CVD or heterozygous familial hypercholesterolemia who require additional LDL lowering, the company stated in the release.

Approval was based on the ORION-9, ORION-10 and ORION-11 phase 3 trials, which demonstrated inclisiran reduced LDL by up to an additional 52% in the patient population for which the drug is now indicated, with a safety profile comparable to placebo, according to the release.

Norman Lepor

“ASCVD is a substantial public health burden affecting 30 million Americans,” Norman Lepor, MD, clinical professor of medicine at UCLA Geffen School of Medicine, attending cardiologist at Cedars-Sinai Heart Institute, co-director of Cardiovascular Imaging-Westside Medical Center, director of clinical research at Westside Medical Associates of Los Angeles and a clinical investigator in the phase 3 clinical program for inclisiran, said in the release. “As a first-of-its-kind siRNA therapy, Leqvio works differently than other cholesterol treatments, with twice-yearly dosing that makes it a compelling option for the millions of people with ASCVD already on cholesterol-lowering medications struggling to reach their LDL-C target.”

PERSPECTIVE

 Michael Davidson, MD)

Michael H. Davidson, MD, FACC, FACP, FNLA

As a preventive cardiologist, I am very excited about the approval of inclisiran. The ability to dose the patients in the clinic every 6 months is a transformative therapy that will help clinicians to mandate compliance. Compliance to the appropriate therapies is a major hurdle for LDL guideline adherence.

My concern is that the annual price tag of $6,500 will require prior authorization, and most primary care physicians or general cardiologists may not want to allocate the resources necessary to make this novel model for lipid management work in their offices.

FDA issues EUA for Merck’s COVID-19 antiviral molnupiravir

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The FDA has issued an emergency use authorization for molnupiravir — now the second oral antiviral treatment available for COVID-19.

The drug is authorized for the treatment of mild-to-moderate COVID-19 in adults who test positive for SARS-CoV-2, and who are at high risk for progression to severe disease. It is not authorized for use in patients aged younger than 18 years because it may affect bone and cartilage growth, the agency said.

Source: Adobe Stock.

FDA’s Antimicrobial Drugs Advisory Committee endorsed a recommendation for granting an EUA in a split 13-10 vote on Nov. 30. The recommendation extended to individuals with COVID-19 who are at high risk for serious illness.

“The EUA for molnupiravir is a sign of progress, since it ushers in an era of oral antivirals that can be used by individuals at increased risk of severe disease (elderly and/or immunocompromised patients) when first diagnosed with SARS-CoV-2,” Kenneth H. Mayer, MD, the medical research director of Fenway Health and codirector of the Fenway Institute, told Healio. “This may become similar to how drugs like Tamiflu are used for patients who develop influenza.”

On Wednesday, the FDA granted an EUA for Pfizer’s Paxlovid, an antiviral that was also developed for the treatment of adults who are at risk for severe COVID-19, but it can also be used to treat pediatric patients aged 12 years and older weighing at least 40 kg, or about 88 pounds.

Molnupiravir, which was developed by Merck in collaboration with Ridgeback Biotherapeutics, reduces the risk for hospitalization or death from COVID-19 among high-risk patients, according to phase 3 data. Merck and Ridgeback Biotherapeutics submitted an EUA application on Oct. 11. Since then, Merck has begun manufacturing capsule pills of molnupiravir. The company expects to have 10 million treatment courses produced by the end of the year. With the EUA, the drug may be available to patients within weeks.

“We’re hopeful that we can make a meaningful impact on the pandemic through the development of an effective oral antiviral COVID-19 medicine, pending regulatory discussions,” a Merck spokesperson told Healio.

The drug’s authorization was supported by a phase 3, double-blind, randomized, placebo-controlled trial called MOVe-OUT. The study included patients aged 18 years or older with a chronic medical condition or an increased risk for SARS-CoV-2 infection who had not received a vaccine. Among the 709 participants who received molnupiravir, 6.8% were hospitalized or died during a 1-month period vs. 9.7% of the 699 people who received a placebo. Results of the trial, published in The New England Journal of Medicine, showed that the rate of hospitalization or death through day 29 was approximately 31% lower with molnupiravir than with placebo (HR = 0.69; 95% CI, 0.48 to 1.01).

In comparison, Pfizer’s investigational oral antiviral, Paxlovid, reduced the risk for COVID-19-related hospitalization and death by almost 90% among patients who received the antiviral within days of experiencing symptoms, Healio previously reported.

Of the participants who received molnupiravir, one died during the follow-up period compared with nine people who received placebo. According to the FDA, adverse events included diarrhea, nausea and dizziness.

The drug’s safety and efficacy continue to be evaluated, the agency said.

Reference:

Bernal AJ, et al. N Engl J Med. 2021;doi:10.1056/NEJMoa2116044.

Getting to the heart of COVID-19-related cardiac injury

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The ability of COVID-19 to cause cardiac injury and myocarditis has been well documented since the pandemic began, and data continue to accumulate.

“We certainly know that COVID-19 has a long-term effect, or ‘long COVID’, which is the systemic disease that even patients with mild COVID-19 can develop,” Howard J. Eisen, MD, senior advanced heart failure specialist at Penn State Medical Center, told Cardiology Today. “They can be fatigued, have a shortness of breath, drops in blood pressure, elevated heart rates. And a lot of that is thought to maybe be due to autoimmune phenomena and enhanced inflammation. But one thing we know is that myocarditis can, in some patients, develop into heart failure. A lot of these patients who we see who have what we call idiopathic dilated cardiomyopathy … we suspect that they have myocarditis.”Leslie T. Cooper Jr., MD, FAHA, from Mayo Clinic in Jacksonville, Florida, discusses current knowledge of cardiac injury related to COVID-19. Source: Paul Najlis/Mayo Clinic. Printed with permission.

As research continues and new information evolves, Cardiology Today spoke with experts in the field about COVID-19-related outcomes on the heart, the risks for myocardial injury as a result of COVID-19 and with vaccination, based on the current knowledge base, and more.

‘A spectrum of injury’

Numerous studies have reported cardiac injury as a result of COVID-19.

Early reports uncovered evidence of cardiac injury in 25% to 30% of patients hospitalized for COVID-19, Biykem Bozkurt, MD, PhD, FHFSA, FACC, FAHA, FESC, Mary and Gordon Cain Chair and Professor of Medicine, director of the Winters Center for HF Research and associate director of the Cardiovascular Research Institute at Baylor College of Medicine, said during a presentation at the Heart in Diabetes meeting in September. Additionally, cardiac injury was most common among patients with preexisting CVD, and elevated levels of CVD biomarkers such as troponin were associated with mortality, Bozkurt said.

“COVID-19 myocarditis is in many ways similar to myocarditis caused by other viruses, but the SARS-CoV-2 virus stands out through its predilection for ACE2 receptors, present in the endothelium as well as in many other organs,” Mariska Kemna, MD, heart failure and transplant cardiologist at Seattle Children’s Hospital and professor of pediatrics at the University of Washington School of Medicine, told Cardiology Today. “SARS-CoV-2 also appears to be more immunogenic than other viruses, leading to severe multi-organ disease in adults and multisystem inflammatory syndrome in children and teens. A hyperimmune response to vaccinations may be part of that clinical picture as well.”

In a study published in the European Heart Journal in May, myocardial injury was detected in more than half of patients hospitalized with severe COVID-19, and elevated cardiac troponin persisted months after hospital discharge.Mariska Kemna

“Troponin levels are easy to obtain. While an elevated level indicates cardiac injury, it does not necessarily equate to myocarditis,” Kemna told Cardiology Today. “Myocarditis can present in many different ways. For COVID-19, cardiac inflammation may be part of a multi-organ inflammatory response or there may be endotheliitis leading to cardiac injury, and it can be challenging to distinguish between those and true myocarditis.”

Researchers continue to investigate the mechanisms underlying COVID-19-related myocardial injury as well as the direct effect of COVID-19 on the heart.

In the Sept. 3 issue of the CDC’s Morbidity and Mortality Weekly Report, researchers reported the incidence of myocarditis in a database of more than 900 hospitals was 42% higher in 2020 compared with 2019, and from March 2020 to January 2021, the risk for myocarditis in patients with COVID-19 was 16 times greater compared with patients without COVID-19.

In another analysis published in JAMA Cardiology in May, researchers evaluated the prevalence of post-COVID-19 myocarditis among collegiate athletes using the Big Ten COVID-19 Cardiac Registry. After cardiac MRI, approximately 2.3% of athletes were diagnosed with clinical or subclinical myocarditis.

In that study, “It became clear that a small percentage of people, maybe 4.5% in the older population with preexisting heart disease and a smaller percentage of young athletes, could actually have myocarditis as defined by a cardiac MRI, and that the majority of the cardiac injury was due to other mechanisms,” Leslie T. Cooper Jr., MD, FAHA, professor of medicine and chair of the cardiovascular department at Mayo Clinic in Jacksonville, Florida, and past president of the Myocarditis Foundation, told Cardiology Today. “Other mechanisms of cardiac injury include blocked large and small arteries, demand ischemia or cytokine storm, in which the heart function is depressed because of systemic inflammatory mediators, as well as another, not yet defined group of novel mechanisms, which could be virus-specific. We and others have shown that the spike protein, which is produced by the virus, can cause cardiac damage directly in isolated heart cells, but without any myocarditis. There’s a spectrum of injury mechanisms, a minority of which is due to classic myocarditis.”

Cardiac injury in pediatric patients

In the MMWR study, risk for myocarditis in patients with COVID-19 was higher among men than women (0.187% vs. 0.109%), was higher in children younger than 16 years (0.133%) and was elevated in adults aged 50 to 64 years (0.155%), 65 to 74 years (0.186%) or 75 years or older (0.238%).

“As of July 9, 2021, there were more than 4 million cases of COVID-19 in children and at least 335 deaths. As of October 14, the total number of COVID-19 cases in children was even higher at 6.2 million,” Sandra Adamson Fryhofer, MD, adjunct professor of medicine at Emory University School of Medicine, and the AMA liaison to the CDC Advisory Committee on Immunization Practices, told Cardiology Today. “Young people with COVID-19 are at risk for multisystem inflammatory syndrome in children and for post-COVID-19 conditions, including persisting symptoms, such as fatigue, insomnia, rhinorrhea, muscle pain, headache, lack of concentration, exercise intolerance, dyspnea and chest pain. It seems adolescents and young adults can have long COVID-19, too.”

The American Heart Association July scientific statement on the diagnosis and management of myocarditis in children indicated that myocarditis in children is most commonly caused by viral infection, although there are a variety of noninfectious causes, and this risk is highest among infants and young adults. According to the statement, pediatric myocarditis is typically acute or sudden-onset and less likely to be chronic compared with adult myocarditis.

Multisystem inflammatory syndrome in children (MIS-C) is a serious potential complication after COVID-19 infection, according to a report published by Nemours Children’s Health.

“Children with COVID-19 can present with MIS-C around 4 to 6 weeks after they’ve had COVID-19 and sometimes they didn’t even realize they had COVID-19,” Kemna told Cardiology Today. “There are instances when they can get critically ill from MIS-C, and require inotropic support or mechanical ventilation, all due to an overactivation of their immune system. Fortunately, it responds well to anti-inflammatory therapy such as IV immunoglobin and steroids. While they can become extremely ill quickly, sometimes even overnight, they often recover just as quickly.”

Causes of myocarditis

COVID-19 is not the only cause of myocarditis.

According to the Myocarditis Foundation, although the leading trigger is viral infections, cancer, bacterial infections and exposure to environmental toxins can also cause myocarditis.

“Common causes of ‘traditional’ myocarditis include infectious agents — viral, bacterial, fungal, parasitic, protozoal — and noninfectious agents, including toxins, certain medications and immunological syndromes,” Fryhofer told Cardiology Today. “In general, we see a gradual increase in the incidence of myocarditis with age, with 76% of adult cases in males. However, children can also suffer myocarditis. The annual incidence in children is 0.8 per 100,000 and is more common in males.”

Compared with myocarditis as a result of H1N1 influenza or coxsackie B myocarditis, “COVID-19-related myocarditis is not as severe. Overall, COVID-19 tends to cause a milder injury with faster recovery,” Cooper told Cardiology Today. “Although, there is a small percentage of people who are critically ill and there is also a small percentage of people who go on to have a more chronic recurrent pattern over months to years of chest pain. That is true for all forms of myocarditis, including, as far as we know, COVID-19-related myocarditis.”

Troponin testing and cardiac MRI are not routinely conducted for most other viral infections, according to a commentary by Maleszewski and colleagues published in Circulation in September 2020. There is a need for more clinical data to effectively compare COVID-19-related myocarditis with myocarditis caused by other infections and diseases.

“It’s well known that the flu and a number of other viruses [can cause myocarditis], so there’s no reason why COVID-19 couldn’t either,” Eisen said. “It’s thought COVID-19 may do a number of things. It may directly damage the heart muscle cells, and we can actually see that on MRI. It can also directly affect the endothelial cells, and therefore can damage to the circulation and can cause clots in those arteries, too.”Howard J. Eisen

According to the AHA scientific statement on myocarditis, the signs of fulminant myocarditis can vary with or without manifestations of an inflammatory disorder or infection. Timely diagnosis and treatment are critical. The first test for myocarditis should be echocardiography, which can rapidly process a diagnosis, and cardiac MRI in this population should be considered secondary since most patients would be too sick to have an MRI, and biopsy is more important.

Vaccines and myocarditis

On May 27, the CDC issued a statement on the possible association between COVID-19 vaccination and risk for myocarditis for both of the available messenger RNA (mRNA) vaccines.

“There is risk for myocarditis after mRNA COVID-19 vaccines, but myocarditis can also occur with COVID-19 infection, and it occurs at higher rates after COVID-19 infection than after mRNA vaccination,” Fryhofer told Cardiology Today. “Data reviewed at the recent Advisory Committee on Immunization Practices meeting on Aug. 30, 2021, revealed patients with COVID-19 had 16 to 18 times higher risk for myocarditis compared to those without COVID-19. Risk did vary by age and sex. Risk of myocarditis due to COVID-19 infection was six to 34 times higher compared to those who received an mRNA vaccine.”

Researchers continue to investigate the link. Recent research suggests that although COVID-19 mRNA vaccines can be associated with myocarditis, particularly in male adolescents and young adults, the incidence is very low, and the severity is usually less than that of COVID-19-induced myocarditis and other cardiac injuries.

Some of the recent research includes a nationwide study published in October in The New England Journal of Medicine. The Pfizer-BioNTech mRNA COVID-19 vaccine was not associated with risk for most adverse events; however, the vaccine was associated with risk for myocarditis of between one and five events per 100,000 persons.

In October, a retrospective analysis published in NEJM utilized the Clalit Health Services database to identify 2.5 million individuals in Israel who received the Pfizer-BioNTech mRNA vaccine, of whom 54 met the criteria for myocarditis. The estimated incidence of myocarditis among individuals who received at least one dose of the vaccine was 2.13 per 100,000 persons, with the highest incidence reported among young men aged 16 to 29 years.

The researchers acknowledged the incidence rates were higher than those reported elsewhere. “Although we cannot directly compare the incidence of myocarditis after vaccination in our study with the incidence in other studies, our data may provide points of reference,” Guy Witberg, MD, interventional cardiologist at the Rabin Medical Centre in Petah-Tikva, Israel, and colleagues wrote. “On the basis of data from the Vaccine Adverse Event Reporting System, the CDC has estimated that the incidence of myocarditis after any COVID-19 vaccination is 0.48 cases per 100,000 overall and 1.2 cases per 100,000 among vaccine recipients between the ages of 18 and 29 years. These estimates are lower than those in our study, possibly due to different methods that were used to identify cases (passive reporting to the CDC vs. electronic health records in our health care organization).”

A similar study from Israel, also published in NEJM in October, estimated that the rate ratio of myocarditis at 30 days after the second dose of the Pfizer-BioNTech vaccine was 2.35 compared with unvaccinated individuals. Again, the incidence was highest for young men aged 16 to 19 years, compared with unvaccinated young men.

A research letter published in October in JAMA Internal Medicine evaluated excess risk for myocarditis as a result of COVID-19 vaccination among more than 2.3 individuals who received at least one dose of the Pfizer-BioNTech or Moderna vaccine. The researchers reported a myocarditis incidence of 5.8 per 1 million individuals after the second dose, or one case per 172,414 fully vaccinated individuals. However, due to the observational nature of this analysis, the researchers stated that no associations between COVID-19 vaccination and incident myocarditis can be established.

“One hypothesis that has been postulated is so-called molecular mimicry, in which parts of the spike proteins that are being expressed as a result of mRNA vaccination are similar to some myocardial proteins, and the antibodies we make in response to the spike protein could cross-react with myocardial proteins,” Kemna told Cardiology Today. “The other hypothesis is that the spike proteins that we produce as a result of mRNA vaccination could bind directly to the ACE2 receptors, activating the inflammatory response in the same manner the virus can.”

According to a presentation at the Aug. 30 CDC Advisory Committee on Immunization Practices meeting by John R. Su, MD, PhD, MPH, Vaccine Adverse Event Reporting System (VAERS) team lead at the CDC and a member of the Vaccine Safety Team of the CDC’s COVID-19 Vaccine Task Force, there had been more than 2,500 reports to VAERS of myocarditis or pericarditis (out of more than 350 million doses of mRNA COVD-19 vaccines administered).

These reports were primarily in younger males, after the second mRNA vaccine dose, and within several days after vaccination. Research and conversations about the impact of COVID-19 on the heart continue.

“It is important to consider myocarditis in young people who experience chest pain, shortness of breath or palpitations after mRNA vaccination,” Fryhofer told Cardiology Today. “Report all cases to VAERS. In the initial evaluation, consider checking ECG, troponin and inflammatory markers like C-reactive protein and erythrocyte sedimentation rate.”Sandra Adamson Fryhofer

In October, the FDA delayed its decision on approving the Moderna vaccine for adolescents aged 12 to 17 years to further review data on vaccine-induced myocarditis risk in that population. The Pfizer-BioNTech vaccine is approved for that age group, and in October was approved for children aged 5 to 11 years.

Importance of vaccination

“It’s clear that vaccination reduces your chance of getting myocarditis,” Kemna told Cardiology Today. “You can get myocarditis from the vaccine, but you can also get myocarditis from COVID-19, even if you’re not in the hospital, you’re not terribly ill and you might never have known that you had it unless you had an MRI.”

The AHA/American Stroke Association released a statement in early November urging adults and children aged 5 years and older to receive a COVID-19 vaccine.

“Vaccination at the individual and the population level is essential to minimize the impact of COVID-19 and people should not avoid vaccination because of a fear of vaccine-related cardiac injury,” Cooper told Cardiology Today.

“In rare occasions, the vaccine may cause some inflammation in the heart, but not anything like what COVID-19 does, and COVID-19 does all sorts of other horrible things,” Eisen told Cardiology Today. “We know that 99% of patients who are dying, hospitalized, intubated and on ventilators in this country are unvaccinated. There’s a certain amount of fatigue among nurses and physicians taking care of people who could prevent all of this by just getting vaccinated. We’ve conquered other diseases such as polio and smallpox, all of which were catastrophic in their day, and we did it through vaccination. I urge people to get vaccinated.” – by Scott Buzby

MI risks elevated during holidays, so heart-healthy practices needed

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More people die from MI between December 25 and January 1 than any other time of year, according to a press release from the American Heart Association.

“The holidays are a busy, often stressful, time for most of us. Routines are disrupted; we may tend to eat and drink more and exercise and relax less. We also may not be listening to our bodies or paying attention to warning signs, thinking it can wait until after the new year. All of these can be contributors to increasing the risk for heart attack at this time of the year,” Donald Lloyd-Jones, MD, ScM, FAHA, president of the American Heart Association and Eileen M. Foell Professor of Heart Research, professor of preventive medicine, medicine and pediatrics, and chair of the department of preventive medicine at Northwestern University’s Feinberg School of Medicine, said in the release.

Holidaysnowflake

According to the release, the AHA recommends that people:

  • Know the symptoms of MI and take immediate action to prevent heart damage and increase chance of survival.
  • Be mindful of diet and alcohol consumption can keep the heart healthy; don’t forget to watch the sodium.
  • Take care of oneself and reduce stress brought on during the holiday season.
  • Stay active by going for a walk or doing fun activities with loved ones, a recommended 150 minutes minimum of physical activity a week.
  • Take medication in a timely manner every day.

MI risk “may be even more likely for many people who didn’t get to be with family and friends last year due to COVID-19 restrictions. It’s incredibly important to be aware of these risks. Take a few simple steps that can help keep you heart healthy with much to celebrate in the new year,” Lloyd-Jones said in the release.

When North Goes South: Is Earth’s Magnetic Field Flipping? | Discover Magazine

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When North Goes South: Is Earth’s Magnetic Field Flipping? | Discover Magazine https://www.discovermagazine.com/planet-earth/when-north-goes-south-is-earths-magnetic-field-flipping?utm_source=dscfb&utm_medium=social&utm_campaign=dscfb

Merry X Mas.

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Merry X mas and season greetings to all my blog subscribes,followers and readers.

Stay connected.

Dr Chandan Aryan.

How to Start All over and Rebuild Your Life from Scratch.

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How to Start All over and Rebuild Your Life from Scratch – Purpose Fairy https://www.purposefairy.com/74960/how-to-start-all-over/

Earth is spinning FASTER now than it was 50 years ago, scientists say

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Earth is spinning FASTER now than it was 50 years ago, scientists say https://www.msn.com/en-us/news/technology/earth-is-spinning-faster-now-than-it-was-50-years-ago-scientists-say/ar-AAS1myr

James Webb Space Telescope will illuminate these 5 cosmic targets

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James Webb Space Telescope will illuminate these 5 cosmic targets https://www.inverse.com/science/what-are-the-main-targets-for-james-webb?utm_campaign=fbproliqinverse&utm_content=2e8MTQ0&utm_medium=pro&utm_source=facebook&lsid=mnymtg1nty