Bellerophon Therapeutics (NASDAQ:BLPH) has submitted an Investigational New Drug (IND) application to the FDA seeking sign-off for an open-label study evaluating INOpulse inhaled nitric oxide therapy in COVID-19 patients who require supplemental oxygen.
Akers Biosciences (AKER+11.8%) perks up on double normal volume in reaction to its announcement that
it, and collaboration partner Premas Biotech, have successfully
expressed three coronavirus antigens (spike, envelope and membrane) that
they selected for their vaccine candidate, the second milestone in
their partnership.
Two days ago, it announced that they had cloned the three antigens which was the first milestone.
Citing COVID-disruptions that have dampened da
Vinci procedure growth, especially in mid-March onward, Intuitive
Surgical (NASDAQ:ISRG) has withdrawn its 2020 financial and procedure guidance.
On a preliminary basis, global da Vinci procedures
in Q1 were up ~10% from a year ago (procedures were up ~19% in Q4
2019). It shipped 237 da Vinci systems in the quarter, up 2 units from
last year.
Management will host its Q1 earnings call on Thursday, April 16, after the close.
Nano cap Moleculin Biotech (NASDAQ:MBRX) announces the results of in vitro
testing in Germany showing that 2-deoxy-D-glucose (2-DG) totally
stopped the replication of the SARS-CoV-2 virus. Specifically,
researchers at the University of Frankfurt reported that inhibiting
glycolysis (sugar metabolism) with non-toxic concentrations of 2-DG
prevented the coronavirus from replicating in cell culture. 2-DG
inhibits glycolysis because it is a decoy that cannot be converted into
energy.
The company’s WP112 candidate is a prodrug of 2-DG
(a prodrug is an inactive compound that is metabolized in the body to
produce the active drug) that, it says, may have therapeutic potential
in COVID-19 since 2-DG in its normal state is metabolized too quickly to
be effective. WP112 is only metabolized once it is inside the cell,
enabling much higher tissue and organ concentrations of 2-DG.
An IND filing, clearing the way for clinical studies, is next up.
Even as hospitals and governors raise the alarm about a shortage of ventilators,
some critical care physicians are questioning the widespread use of the
breathing machines for Covid-19 patients, saying that large numbers of
patients could instead be treated with less intensive respiratory
support.
If the iconoclasts are right, putting coronavirus patients on
ventilators could be of little benefit to many and even harmful to some.
What’s driving this reassessment is a baffling observation about
Covid-19: Many patients have blood oxygen levels so low they should be
dead. But they’re not gasping for air, their hearts aren’t racing, and
their brains show no signs of blinking off from lack of oxygen.
That is making critical care physicians suspect that blood levels of
oxygen, which for decades have driven decisions about breathing support
for patients with pneumonia and acute respiratory distress, might be
misleading them about how to care for those with Covid-19. In
particular, more and more are concerned about the use of intubation and
mechanical ventilators. They argue that more patients could receive
simpler, noninvasive respiratory support, such as the breathing masks
used in sleep apnea, at least to start with and maybe for the duration
of the illness.
“I think we may indeed be able to support a subset of these patients”
with less invasive breathing support, said Sohan Japa, an internal
medicine physician at Boston’s Brigham and Women’s Hospital. “I think we
have to be more nuanced about who we intubate.”
That would help relieve a shortage of ventilators so critical that
states are scrambling to procure them and some hospitals are taking the
unprecedented (and largely untested) step of using a single ventilator
for more than one patient. And it would mean fewer Covid-19 patients,
particularly elderly ones, would be at risk of suffering the long-term
cognitive and physical effects of sedation and intubation while being on
a ventilator.
None of this means that ventilators are not necessary in the Covid-19
crisis, or that hospitals are wrong to fear running out. But as doctors
learn more about treating Covid-19, and question old dogma about blood
oxygen and the need for ventilators, they might be able to substitute
simpler and more widely available devices.
An oxygen saturation rate below 93% (normal is 95% to 100%) has long
been taken as a sign of potential hypoxia and impending organ
damage. Before Covid-19, when the oxygen level dropped below this
threshold, physicians supported their patients’ breathing with
noninvasive devices such as continuous positive airway pressure (CPAP,
the sleep apnea device) and bilevel positive airway pressure ventilators
(BiPAP). Both work via a tube into a face mask.
In severe pneumonia or acute respiratory distress unrelated to
Covid-19, or if the noninvasive devices don’t boost oxygen levels
enough, critical care doctors turn to mechanical ventilators that push
oxygen into the lungs at a preset rate and force: A physician threads a
10-inch plastic tube down a patient’s throat and into the lungs,
attaches it to the ventilator, and administers heavy and long-lasting
sedation so the patient can’t fight the sensation of being unable to
breathe on his own.
But because in some patients with Covid-19, blood-oxygen levels fall
to hardly-ever-seen levels, into the 70s and even lower, physicians are
intubating them sooner. “Data from China suggested that early intubation
would keep Covid-19 patients’ heart, liver, and kidneys from failing
due to hypoxia,” said a veteran emergency medicine physician. “This has
been the whole thing driving decisions about breathing support: Knock
them out and put them on a ventilator.”
To be sure, many physicians are starting simple. “Most hospitals,
including ours, are using simpler, noninvasive strategies first,”
including the apnea devices and even nasal cannulas, said Greg Martin, a
critical care physician at Emory University School of Medicine and
president-elect of the Society of Critical Care Medicine. (Nasal
cannulas are tubes whose two prongs, held beneath the nostrils by
elastic, deliver air to the nose.) “It doesn’t require sedation and the
patient [remains conscious and] can participate in his care. But if the
oxygen saturation gets too low you can achieve more oxygen delivery with
a mechanical ventilator.”
The question is whether ICU physicians are moving patients to
mechanical ventilators too quickly. “Almost the entire decision tree is
driven by oxygen saturation levels,” said the emergency medicine
physician, who asked not to be named so as not to appear to be
criticizing colleagues.
That’s not unreasonable. In patients who are on ventilators due to
non-Covid-19 pneumonia or acute respiratory distress, a blood oxygen
level in the 80s can mean impending death, with no room to give
noninvasive breathing support more time to work. Physicians are using
their experience with ventilators in those situations to guide their
care for Covid-19 patients. The problem, critical care physician Cameron
Kyle-Sidell told Medscape
this week, is that because U.S. physicians had never seen Covid-19
before February, they are basing clinical decisions on conditions that
may not be good guides.
“It’s hard to switch tracks when the train is going a million miles
an hour,” said Kyle-Sidell, who works at a New York City hospital. “This
may be an entirely new disease,” making ventilator protocols developed
for other conditions less than ideal.
As doctors learn more about the disease, however, both frontline
experience and a few small studies are leading him and others to
question how, and how often, mechanical ventilators are used for
Covid-19.
The first batch of evidence relates to how often the machines fail to
help. “Contrary to the impression that if extremely ill patients with
Covid-19 are treated with ventilators they will live and if they are
not, they will die, the reality is far different,” said geriatric and
palliative care physician Muriel Gillick of Harvard Medical School.
Researchers in Wuhan, for instance, reported that, of 37 critically ill Covid-19 patients who were put on mechanical ventilators, 30 died within a month. In a U.S. study
of patients in Seattle, only one of the seven patients older than 70
who were put on a ventilator survived; just 36% of those younger than 70
did. And in a study
published by JAMA on Monday, physicians in Italy reported that nearly
90% of 1,300 critically ill patients with Covid-19 were intubated and
put on a ventilator; only 11% received noninvasive ventilation.
One-quarter died in the ICU; 58% were still in the ICU, and 16% had been
discharged.
Older patients who do survive risk permanent cognitive and
respiratory damage from being on heavy sedation for many days if not
weeks and from the intubation, Gillick said.
To be sure, the mere need for ventilators in Covid-19 patients
suggests many in the studies were so critically ill their chances of
survival were poor no matter what care they received.
But one of the most severe consequences of Covid-19 suggests another
reason the ventilators aren’t more beneficial. In acute respiratory
distress syndrome, which results from immune cells ravaging the lungs
and kills many Covid-19 patients, the air sacs of the lungs become
filled with a gummy yellow fluid. “That limits oxygen transfer from the
lungs to the blood even when a machine pumps in oxygen,” Gillick said.
As patients go downhill, protocols developed for other respiratory
conditions call for increasing the force with which a ventilator
delivers oxygen, the amount of oxygen, or the rate of delivery, she
explained. But if oxygen can’t cross into the blood from the lungs in
the first place, those measures, especially greater force, may prove
harmful. High levels of oxygen impair the lung’s air sacs, while high
pressure to force in more oxygen damages the lungs.
In a letter
last week in the American Journal of Respiratory and Critical Care
Medicine, researchers in Germany and Italy said their Covid-19 patients
were unlike any others with acute respiratory distress. Their lungs are
relatively elastic (“compliant”), a sign of health “in sharp contrast to
expectations for severe ARDS.” Their low blood oxygen might result from
things that ventilators don’t fix. Such patients need “the lowest
possible [air pressure] and gentle ventilation,” they said, arguing
against increasing the pressure even if blood oxygen levels remain low.
“We need to be patient.”
“We need to ask, are we using ventilators in a way that makes sense
for other diseases but not for this one?” Gillick said. “Instead of
asking how do we ration a scarce resource, we should be asking how do we
best treat this disease?”
Researchers and clinicians on the front lines are trying. In a small study
last week in Annals of Intensive Care, physicians who treated Covid-19
patients at two hospitals in China found that the majority of patients
needed no more than a nasal cannula. Among the 41% who needed more
intense breathing support, none was put on a ventilator right away.
Instead, they were given noninvasive devices such as BiPAP; their blood
oxygen levels “significantly improved” after an hour or two. (Eventually
two of seven needed to be intubated.) The researchers concluded that
the more comfortable nasal cannula is just as good as BiPAP and that a
middle ground is as safe for Covid-19 patients as quicker use of a
ventilator.
“Anecdotal experience from Italy [also suggests] that they were able
to support a number of folks using these [non-invasive] methods,” Japa
said.
To be “more nuanced about who we intubate,” as she suggests, starts
with questioning the significance of oxygen saturation levels. Those
levels often “look beyond awful,” said Scott Weingart, a critical care
physician in New York and host of the “EMCrit” podcast. But many can
speak in full sentences, don’t report shortness of breath, and have no
signs of the heart or other organ abnormalities that hypoxia can cause.
“The patients in front of me are unlike any I’ve ever seen,”
Kyle-Sidell told Medscape about those he cared for in a hard-hit
Brooklyn hospital. “They looked a lot more like they had altitude
sickness than pneumonia.”
Because U.S. data on treating Covid-19 patients are nearly
nonexistent, health care workers are flying blind when it comes to
caring for such confounding patients. But anecdotally, Weingart said,
“we’ve had a number of people who improved and got off CPAP or high flow
[nasal cannulas] who would have been tubed 100 out of 100 times in the
past.” What he calls “this knee-jerk response” of putting people on
ventilators if their blood oxygen levels remain low with noninvasive
devices “is really bad. … I think these patients do much, much worse on
the ventilator.”
That could be because the ones who get intubated are the sickest, he
said, “but that has not been my experience: It makes things worse as a
direct result of the intubation.” High levels of force and oxygen
levels, both in quest of restoring oxygen saturation levels to normal,
can injure the lungs. “I would do everything in my power to avoid
intubating patients,” Weingart said.
One reason Covid-19 patients can have near-hypoxic levels of blood
oxygen without the usual gasping and other signs of impairment is that
their blood levels of carbon dioxide, which diffuses into air in the
lungs and is then exhaled, remain low. That suggests the lungs are still
accomplishing the critical job of removing carbon dioxide even if
they’re struggling to absorb oxygen. That, too, is reminiscent of
altitude sickness more than pneumonia.
The noninvasive devices “can provide some amount of support for
breathing and oxygenation, without needing a ventilator,” said ICU
physician and pulmonologist Lakshman Swamy of Boston Medical Center.
One problem, though, is that CPAP and other positive-pressure
machines pose a risk to health care workers, he said. The devices push
aerosolized virus particles into the air, where anyone entering the
patient’s room can inhale them. The intubation required for mechanical
ventilators can also aerosolize virus particles, but the machine is a
contained system after that.
“If we had unlimited supply of protective equipment and if we had a
better understanding of what this virus actually does in terms of
aerosolizing, and if we had more negative pressure rooms, then we would
be able to use more” of the noninvasive breathing support devices, Swamy
said.
As they became inundated with patients suffering severe respiratory
distress from the coronavirus last month, a group of nurses at a Long
Island hospital snapped into action and created a “turning team.”
The eight-member squad at Huntington Hospital — including nurses,
doctors and orderlies — works to turn critically ill patients in the
throes of COVID-19 on their stomachs to allow gravity to remove mucus
buildup in their lungs.
“We think this is helpful because in other similar lung conditions,
we have found it to work in the past,” said Michael Grosso, the medical
director. “Keeping patients prone opens both the airways and gets more
oxygen into air sacs and improves circulation to the lungs.”
The relatively simple procedure, which is also being used in some
New York City hospitals when overwhelmed staff is available, was found
to help patients at the epicenter of the outbreak in Wuhan, China, according to a study published last week by the American Thoracic Society’s “American Journal of Respiratory and Critical Care Medicine.”
A lung specialist at NYU Langone told The Post that the hospital is “proning patients” both in and out of intensive care.
“Most of the proning we are doing is manual and takes several people to do,” said Dr. Daniel Sterman.
Although some hospitals have special beds that will turn the patients
automatically, patients who are intubated and hooked up to a respirator
and other life-saving devices need to be turned manually, with the aid
of a dedicated team, health care professionals said.
“Don’t forget that these are patients who are usually already
receiving mechanical ventilation, with a breathing tube in their wind
pipe, and tubes that are placed into their blood vessels, and when you
are turning a patient under those circumstances, it requires several
people,” said Grosso, whose 270-bed hospital has 200 patients suffering
from COVID-19. https://nypost.com/2020/04/04/lung-draining-turning-teams-may-be-step-in-covid-19-care/
U.S. stock index futures swung up and down, searching for direction
late Tuesday, following another volatile day on Wall Street. As of 10:15
p.m. Eastern, Dow Jones Industrial Average futures YM00, -0.12%
were about flat, after rising as more than 100 points then falling more
than 200 points earlier in the session. S&P 500 futures ES00, 0.02% and Nasdaq-100 futures NQ00, 0.27%
also bounced around. Earlier in the day, stocks finished lower, falling
from intraday highs, thwarting a second straight session of gains
despite signs that the COVID-19 pandemic may be leveling off in parts of
the world. The Dow DJIA, -0.11% closed down 26 points. https://www.marketwatch.com/story/us-stock-futures-seek-direction-in-volatile-session-2020-04-07
