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University Of Pittsburgh School Of Medicine Researcher Discovers How Coronavirus Causes Harmful Inflammation

PITTSBURGH (KDKA) — A researcher at the University of Pittsburgh School of Medicine has discovered how coronavirus can cause harmful and escalating inflammation.

It is because of a region on the spike protein she calls a superantigen.

“That region would be expected to trigger a very strong response, adaptive immune response, and now the response is so exaggerated,” says Ivet Bahar, Ph.D., distinguished professor and John K. Vries Chair of computational and systems biology at Pitt School of Medicine.

Her work came about by trying to get a better handle on what happens in the severe pediatric coronavirus-related illness MIS-C or multisystem inflammatory syndrome in children. The symptoms of low blood pressure, fever and rash looked very similar to toxic shock syndrome, a potentially fatal illness caused by bacterial toxins.



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By using computer models, she found a surprise.

“We started to compare the sequence and structure to existing superantigens, bacterial toxins, and found that there is a region that is very similar to a known bacterial toxin,” says Dr. Bahar.

This segment of the spike protein causes an excessive reaction in certain immune system cells and signals. This overreaction can lead to organ damage. Collaborators in Germany were able to show how her computer discovery actually happens in real-life patients.

“We know now that it’s not only children, we are observing the same phenomenon with also adults with severe COVID-19,” Dr. Bahar says.

But why it only happens in some people is still a mystery.

“Different people react in different ways somehow,” says Dr. Bahar. “That is something to further explore.”

The next step is to develop treatments to target the superantigen. Dr. Bahar hopes existing antibodies that target bacterial toxins might work.

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Intensive Blood Pressure Lowering Potentially Harmful in ICH

Intensive lowering of systolic blood pressure (SBP) for patients with intracerebral hemorrhage (ICH) whose initial SBP is excessively high does not improve outcomes and is linked to safety concerns, new research shows.

Investigators found that ICH patients whose initial SBP was 220 mmHg and who underwent intensive BP lowering had twice the relative risk for neurologic deterioration at 24 hours without any reduction in hematoma expansion or 3-month risk for death and disability compared to their counterparts who underwent standard SBP lowering.

“The significantly higher rate of neurological deterioration associated with intensive treatment in patients with initial systolic blood pressure of 220 mm Hg or more warrants caution against broad recommendations for intensive systolic blood pressure reduction in patients with intracerebral hemorrhage,” the investigators, led by Iryna Lobanova, MD, Zeenat Qureshi Stroke Institute, University of Missouri, in Columbia, write.

The study was published online September 8 in JAMA Neurology.

Efficacy Unknown

American Heart Association and American Stroke Association guidelines recommend lowering SBP to 140 mmHg for ICH patients whose SBP is between 150 mmHg and 220 mmHg. However, guideline authors note that the safety and efficacy of intensive SBP lowering for patients with SBP >220 mmHg “appears to be unknown.”

To evaluate the safety and efficacy of intensive SBP reduction for ICH patients with excessively high initial SBP, the investigators analyzed data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage–II (ATACH-II) trial, which compared intensive and standard SBP reduction for patients with spontaneous supratentorial ICH.

Eligible participants had SBP >180 mmHg on two measurements. The first measurement that was recorded in the emergency department was considered the initial SBP.

Consistent with practice guidelines, treatment to lower SBP before randomization was permitted. The SBP measurement recorded immediately before randomization was the prerandomization SBP.

The treatment goal was to reduce SBP to a target range of 140 mmHg to 179 mmHg in the standard reduction group and 110 mmHg to 139 mmHg in the intensive reduction group over 24 hours.

The primary outcome was the proportion of patients who died or experienced severe disability at 90 days, defined as a Modified Rankin Scale score of 4 to 6.

Secondary outcomes included neurologic deterioration, as determined by the Glasgow Coma Scale or the NIH Stroke Scale, as well as hematoma expansion and hypotension.

Neurologic Deterioration

The study included 999 participants. Of these, 228 had an initial SBP of ≥220 mmHg. The mean age was significantly less in the excessively high SBP group than in the lower SBP group, at 59.0 and 62.8 years, respectively.

The mean minimum SBP at 6 to 7 hours and at 23 to 24 hours after randomization was significantly higher among the high SBP group than the lower SBP group.

Of the 228 patients whose initial SBP was ≥220 mmHg, 110 were randomly assigned to intensive SBP reduction, and 118 were assigned to standard SBP reduction. These two treatment groups did not differ significantly with respect to age or sex distribution.

Results showed that among participants with excessively high

Trump’s attack on Hunter Biden underscores ‘harmful stigma’ of addiction

Remarks like these perpetuate “a harmful stigma,” said Mark Sutton, spokesman for the nonprofit Drug Policy Alliance, which advocates for the decriminalization of drug use.

“At a time when we have approximately 70,000 people in the United States dying per year from accidental overdose, it is unconscionable that someone vying for our highest elected office would be so willing to throw people struggling with substance-use disorder under the bus,” he added.

Federal data shows that roughly 1 in 10 American adults — or 23 million people — have struggled with a drug-use disorder at some point in their lives. Such a diagnosis is “based on a list of symptoms including craving, withdrawal, lack of control, and negative effects on personal and professional responsibilities,” according to the National Institutes of Health. Drug abuse is not necessarily illicit — many people addicted to opioids obtain them legally through a doctor’s prescription, for instance.

Drug and alcohol abuse often inflict suffering on the affected person’s family members. “By the time most families reach out for help and drug treatment, the disease of addiction has typically progressed to a crisis stage for the addict and family alike,” according to the Hazelden Betty Ford Foundation. The number of Americans with firsthand experience with addiction and dependency is probably much larger than official statistics show.

Drug and alcohol abuse are devastating disorders. Drug overdoses killed approximately 72,000 people in 2019, while excessive drinking is “responsible for more than 95,000 deaths in the United States each year, or 261 deaths per day,” according to the CDC, a figure that includes deaths from chronic alcohol-related illnesses, suicides, alcohol poisoning and drunken-driving crashes.

But according to many experts, the stigma surrounding drug and alcohol abuse is even more deadly.

“I think the biggest killer out there is stigma,” U.S. Surgeon General Jerome Adams said in 2019. “Stigma keeps people in the shadows. Stigma keeps people from coming forward and asking for help. Stigma keeps families from admitting that there is a problem.”

Writing this year in the New England Journal of Medicine, the director of the National Institute on Drug Abuse, Nora Volkow, said that stigmatizing people who use drugs “may be the equivalent of an electric shock in the cycle of drug addiction: it’s a powerful social penalty that spurs further drug taking … respect and compassion are essential.”

Hunter Biden has been open about his substance abuse, chronicling his history of alcohol and drug use — as well as his attempts to get those behaviors under control — for Adam Entous of the New Yorker in 2019. The Biden campaign did not respond to a request for comment.

For many people with a drug or alcohol problem, the support of family members is critical. At the debate, Biden’s response to Trump illustrated what that support looks like.

“My son, like a lot of people, like a lot of people you know at home, had a drug problem,” Biden said. “He’s overtaken it. He’s fixed it. He’s worked