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Cerebral venous thrombosis is a rare form of cerebral circulatory disorder that, unlike classic stroke, more often affects younger people. For unknown reasons, blood clots (thrombi) form in cerebral veins, obstructing blood flow and causing damage to brain tissue. In the spring of 2021, cerebral vein thrombosis came to public attention as a very rare side effect of Corona vaccination with vector-based vaccines. In the meantime, however, epidemiological studies have shown that patients with Covid-19 are at a much higher risk for this serious complication.
Scientists from the Rudolf Virchow Center for Integrative and Translational Bioimaging at the University of Würzburg (RVZ) and the University Hospital Würzburg, who are collaborating with colleagues from Tübingen and Greifswald in the Collaborative Research Center Transregio (SFB TR) 240, have now been able to show for the first time that the activation of two specific receptors on the surface of blood platelets leads to cerebral venous thrombosis. “This surprising finding could be the basis for a new, highly effective therapy for this rare but serious disease,” explains the head of the study, Prof. Dr. Bernhard Nieswandt (Chair of Experimental Biomedicine I), who is also the spokesperson of the SFB TR 240.
Interaction of two platelet receptors leads to cerebral venous thrombosis
Until now, the molecular processes involved in the development of cerebral venous thrombosis were poorly understood, and there were no suitable research models to study them. Known risk factors are puerperium, oral contraception, and infections. “Actually, we wanted to investigate whether an antibody against the receptor CLEC-2 on platelets increases the bleeding tendency when administered into the bloodstream. Quite unexpectedly, the antibody triggered seizures and other neurological deficits in the treated animals in addition to a drop in platelet count. Symptoms that closely resembled those of patients with acute cerebral venous thrombosis. In fact, further investigation showed that the animals had developed severe cerebral venous thrombosis within minutes, without clot formation in other organs,” explained Prof. David Stegner, head of the Vascular Imaging group at RVZ and one of the two first authors of the study. “We hypothesize that the binding of the antibody alters the properties of the CLEC-2 receptor so that it transmits signals into the cell. This activates platelets and they clump together in the cerebral venous circulation, triggering cerebral venous thrombosis. One mystery is why only the cerebral veins are affected,” Stegner adds. The research group found that in addition to CLEC-2, a second platelet receptor, GPIIb/IIIa, is involved in the development of cerebral venous thrombosis and that only the interaction of both receptors leads to thrombus formation in the brain.
Platelet blockade as a new therapeutic approach
With these findings, the researchers now specifically sought active substances to block such cerebral vein thromboses. A blood clot is formed by the combination of two processes: plasmatic coagulation and platelet activation. Treatment of venous thrombosis generally relies on heparin, as an inhibitor of plasmatic coagulation. However, in the cerebral venous thromboses studied here in animal experiments, heparin had only a comparatively small protective effect. Notably, heparin is the standard medication in the acute treatment of patients with cerebral venous thrombosis, except when it occurs as a complication associated with corona vaccination.
The scientists therefore focused on platelet receptors. When these were blocked in advance, cerebral venous thrombosis did not develop. “The most interesting finding, however, was that inhibition of platelets by blocking the GPIIb/IIIa receptor, was extremely effective even after the onset of neurological symptoms, i.e. in the acute course of the disease,” says Vanessa Göb, also first author of the study. The group showed that the receptor blockade immediately stopped the formation of blood clots in the cerebral veins, the treated animals recovered completely and no bleeding complications occurred. This is of considerable importance for a possible transfer of this therapeutic approach to patients. Prof. Guido Stoll of the Department of Neurology adds, “These results were surprising and may pave the way for the use of GPIIb/IIIa blockers in those patients in whom cerebral venous thrombosis progresses despite heparin treatment, often leading to death. GPIIb/IIIa blockers are already approved for other cardiovascular diseases.”
A key to the success of this project was the interdisciplinary collaboration of different research groups within the Collaborative Research Center Transregio 240 “Platelets — Molecular, cellular and systemic functions in health and disease” (Würzburg — Tübingen), which has been funded by the German Research Foundation since 2018.
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Researchers at the University and the University Hospital of Bonn have developed a method that could be used to diagnose atherosclerosis. Using self-learning software, they were able to identify vascular changes in patients with peripheral arterial disease (PAD), often at an early stage. Although these early stages do not yet cause symptoms, they are nevertheless already associated with increased mortality. The algorithm used photos from an organ not normally associated with PAD: the eye. The results have now been published in the journal Scientific Reports.
Poets consider the eyes a window to the soul. But more prosaically, they could also be called windows to our vessels. The fundus of the eye is very well supplied with blood. It has to be, so that the more than 100 million photoreceptors in the retina and the nerve cells connected to them can do their work. At the same time, the arteries and veins can be observed and photographed through the pupil without much effort.
It may be possible to detect early signs of atherosclerosis (hardening of the arteries) with such an examination in the future. In this case, chronic remodeling processes lead to narrowing of the vessels and hardening of the affected arteries. It is the main cause of heart attacks and strokes, the most frequent causes of death in western industrialized nations, as well as peripheral arterial disease (PAD).
More than four million people in this country suffer from PAD. “Because it usually does not cause any symptoms in the first few years, the diagnosis is often only made when secondary damage has already occurred,” explains Dr. Nadjib Schahab, head of the angiology section and one of the authors of the study. “The consequences can be dramatic. In the long term, progressive circulatory problems in the legs and arms may even result in amputation. In addition, the risk of a fatal heart attack or stroke is significantly increased — even in the early stages of the disease.”
Early diagnosis is therefore very important in order to be able to treat those affected in time. The interdisciplinary project of the Department of Informatics at the University of Bonn and the Department of Ophthalmology and the Heart Center of the University Hospital Bonn starts exactly there. “We photographed 97 eyes of women and men who suffered from PAD,” explains Dr. Maximilian Wintergerst from the University Eye Hospital in Bonn. “In more than half of them, the disease was still at a stage where it did not cause any symptoms.” In addition, the team took camera images of the background of 34 eyes of healthy control subjects.
Neural network detects early vascular changes
They then used the images to feed a convolutional neural network (CNN). This is software that is modeled on the human brain in the way it works. If such a CNN is trained with photos whose content is known to the computer, it can later recognize the content of unknown photos. For this to work with sufficient certainty, however, one normally needs several tens of thousands of training photos — far more than were available in the study.
“We therefore first carried out a pre-training with another disease that attacks the vessels in the eye,” explains Prof. Dr. Thomas Schultz from the Bonn-Aachen International Center for Information Technology (b-it) and the Institute for Computer Science II at the University of Bonn. To do this, the researchers used a dataset of more than 80,000 additional photos. “In a sense, the algorithm learns from them what to pay particular attention to,” says Schultz, who is also a member of the Transdisciplinary Research Areas “Modeling” and “Life and Health” at the University of Bonn. “We therefore also speak of transfer learning.”
The CNN trained in this way was able to diagnose with remarkable accuracy whether the eye photos came from a PAD patient or a healthy person. “A good 80 percent of all affected individuals were correctly identified, if we took into account 20 percent false positives — that is, healthy individuals whom the algorithm incorrectly classified as sick,” Schultz explains. “That’s amazing, because even for trained ophthalmologists, PAD can’t be detected from fundus images.”
In further analyses, the researchers were able to show that the neural network pays particular attention to the large vessels in the back of the eye during its assessment. For the best possible result, however, the method needed digital images with a sufficiently high resolution. “Many CNNs work with very low-resolution photos,” Schultz says. “That is sufficient to detect major changes. For our PAD classification, on the other hand, we need a resolution at which details of the vascular structures remain discernible.”
The researchers hope to further improve the performance of their method in the future. To do so, they plan to cooperate with ophthalmology and vascular medicine centers worldwide that will provide them with additional fundus images of affected individuals. The long-term goal is to develop a simple, rapid and reliable diagnostic method that does not require concomitant procedures such as the administration of eye drops.
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Blood clots form naturally as a way to stop bleeding when someone is injured. But blood clots in patients with medical issues, such as mechanical heart valves or other heart conditions, can lead to a stroke or heart attack. That’s why millions of Americans take blood-thinning medications, such as warfarin, that make it harder for their blood to clot.
Warfarin isn’t perfect, however, and requires patients to be tested frequently to make sure their blood is in the correct range — blood that clots too easily could still lead to a stroke or a heart attack while blood that doesn’t clot can lead to extended bleeding after an injury. To be tested, patients either have to go to a clinic laboratory or use a costly at-home testing system.
Researchers at the University of Washington have developed a new blood-clotting test that uses only a single drop of blood and a smartphone vibration motor and camera. The system includes a plastic attachment that holds a tiny cup beneath the phone’s camera.
A person adds a drop of blood to the cup, which contains a small copper particle and a chemical that starts the blood-clotting process. Then the phone’s vibration motor shakes the cup while the camera monitors the movement of the particle, which slows down and then stops moving as the clot forms. The researchers showed that this method falls within the accuracy range of the standard instruments of the field.
The team published these findings Feb. 11 in Nature Communications.
“Back in the day, doctors used to manually rock tubes of blood back and forth to monitor how long it took a clot to form. This, however, requires a lot of blood, making it infeasible to use in home settings,” said senior author Shyam Gollakota, UW professor in the Paul G. Allen School of Computer Science & Engineering. “The creative leap we make here is that we’re showing that by using the vibration motor on a smartphone, our algorithms can do the same thing, except with a single drop of blood. And we get accuracy similar to the best commercially available techniques.”
Doctors can rank blood-clotting ability using two numbers: the time it takes for the clot to form, what’s known as the “prothrombin time” or PT a ratio calculated from the PT that allows doctors to more easily compare results between different tests or laboratories, called the “international normalized ratio” or INR

The highly contagious omicron variant of SARS-CoV-2 became the dominant strain in the United States in mid-December 2021, coinciding with a rise in hospitalizations of patients with COVID-19. Among those admitted during the omicron surge, vaccinated adults had less severe illness compared with unvaccinated adults and were less likely to land in intensive care, according to a new study by Cedars-Sinai and the Centers for Disease Control and Prevention (CDC).
“Overall, the omicron-period group had a lower likelihood of being admitted to the intensive care unit (ICU) and were also less likely to require invasive mechanical ventilation compared with the delta-period group,” said Matthew Modes, MD, a pulmonologist at Cedars-Sinai and co-first author of the paper.
Investigators also found that during the omicron period fewer patients died while hospitalized (4.0%), compared with those admitted when the delta variant was dominant (8.3%).
In a single-hospital study published in the CDC’s Morbidity and Mortality Weekly Report, scientists looked at the characteristics of 339 patients hospitalized with COVID-19 at Cedars-Sinai Medical Center in Los Angeles, from July to September of 2021, when the delta variant of SARS-CoV-2 was dominant. They compared that group with 737 patients admitted with COVID-19 during December 2021-January 2022, when the omicron variant was most prevalent.
Clinical information was gathered from the electronic health records of the patients in the study and then analyzed by a team of investigators led by Sharon Isonaka, MD, MS, chief value officer and vice president for Clinical Efficiency and Value at Cedars-Sinai.
The analysis revealed that a greater portion of the patients hospitalized during omicron were vaccinated as compared to patients hospitalized during the summer of 2021 when the delta variant predominated, likely reflecting the higher percentage of the populations that were vaccinated during omicron.
“In addition to the protection that vaccination offered people admitted to the hospital when omicron dominated, we saw that the addition of a booster dose appeared to be particularly important in reducing the severity of illness, especially among older adults,” said Peter Chen, MD, senior author of the study and director of Pulmonary and Critical Care Medicine at Cedars-Sinai.
“Unvaccinated patients hospitalized with COVID-19 during the omicron variant dominance still had a higher chance of being admitted with serious complications and appeared to be at higher risk for the development of respiratory failure, compared with vaccinated patients,” said Chen, who holds the Medallion Chair in Molecular Medicine and is a professor of Medicine and Biomedical Sciences.
Large numbers of hospitalizations during the pandemic have strained health systems throughout the country. Vaccination, including a booster dose for those who are fully vaccinated, remains critical for mitigating the risk of severe illness associated with SARS-CoV-2 infection.
“A clear pattern emerges if you take just the omicron-period patients and compare their vaccination status against the percentage of them who ended up in the ICU. The more vaccinated someone is-from unvaccinated, partially vaccinated, fully vaccinated without a booster dose to fully vaccinated with a booster dose?the better the outcome for the patient,” said Michael Melgar, MD, a co-first author of the study and a medical officer with the CDC.
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Also known as transcriptional activators for their ability to induce transcription of genes into RNA messages, these proteins are essential for the cells to function properly. Yet little is known about these proteins, and it wasn’t clear how many activators there might be in human cells — until now.
The research was led by Mikko Taipale, an associate professor of molecular genetics in the Donnelly Centre for Cellular and Biomolecular Research at the Temerty Faculty of Medicine, in collaboration with Anne-Claude Gingras, a senior investigator at the Lunenfeld-Tanenbaum Research Institute, Sinai Health System and professor of molecular genetics at U of T.
The work was spearheaded by Taipale’s graduate student Nader Alerasool, who defended his PhD thesis last month — a day after the study was published online in the journal Molecular Cell, and ahead of print publication this week.
In the article, the researchers describe the first unbiased proteome scale study that has expanded the number of known transcriptional activators from a handful to around 250. They have also established how these proteins combine with other cellular machineries to turn genes on, and how protein misregulation can lead to cancer.
“This study was a classic fishing expedition where we did not know what we were going to find,” said Taipale, who holds Canada Research Chair in Functional Proteomics and Protein Homeostasis. “Grant reviewers typically frown upon research that is not hypothesis driven, but that’s the beauty of proteomics. It allows you to cast a net in an unbiased way, and we have found some interesting stuff.
“We now have a better understanding of which proteins are very strong activators. And we can begin to understand the mechanisms by which they activate transcription.”
To find the activators, the researchers tested the majority of 20,000 human proteins for their ability to activate gene expression in human cells. Many activators were transcription factors (TFs), which directly bind DNA and turn on their target genes, whereas others were helper proteins, or co-factors, that bind TFs and activate their targets together.

New research published today in the Journal of Archaeological Science Reports reveals how archaeologists can determine when a pot was used by Romans as a portable toilet, known as a chamber pot.
“Conical pots of this type have been recognized quite widely in the Roman Empire and in the absence of other evidence they have often been called storage jars. The discovery of many in or near public latrines had led to a suggestion that they might have been used as chamber pots, but until now proof has been lacking,” says Roger Wilson, a professor in UBC’s department of classical, Near Eastern and religious studies who directs the Gerace archaeological project in Sicily where the pot was found.
Archaeologists at the University of Cambridge analyzed crusty material formed on the inside surface of a ceramic pot dating to the fifth century from a Roman villa site in Sicily. Using microscopy to identify intestinal parasites, the team from the Ancient Parasites Laboratory identified the eggs of whipworm, confirming that the vessel had once contained human faeces.
“It was incredibly exciting to find the eggs of these parasitic worms 1,500 years after they’d been deposited,” says co-author Tianyi Wang, University of Cambridge, who took part in the microscopy work.
Whipworms are human parasites that are about five centimetres long and live on the lining of our intestines. The eggs they lay get mixed in with the human faeces, and so would be deposited in a chamber pot during use. Minerals from urine and faeces built up in layers on the inner surface of the pot as it was repeatedly used, creating concretions.
“We found that the parasite eggs became entrapped within the layers of minerals that formed on the pot surface, so preserving them for centuries,” says co-author Sophie Rabinow, also of the Cambridge team.

The agency threw out previous recommended limits on doses but encouraged “nonopioid therapies” wherever possible.The federal government on Thursday proposed new guidelines for prescribing opioid painkillers that remove its previous recommended ceilings on doses for chronic pain patients and instead encourage doctors to use their best judgment.But the overall thrust of the recommendations was that doctors should first turn to “nonopioid therapies” for both chronic and acute pain, including prescription medications like gabapentin and over-the-counter ones like ibuprofen, as well as physical therapy, massage and acupuncture.Though still in draft form, the 12 recommendations, issued by the Centers for Disease Control and Prevention, are the first comprehensive revisions of the agency’s opioid prescribing guidelines since 2016. They walk a fine line between embracing the need for doctors to prescribe opioids to alleviate some cases of severe pain while guarding against exposing patients to the well-documented perils of opioids.Dr. Samer Narouze, president of the American Society of Regional Anesthesia and Pain Medicine, an association of clinicians, praised the tone, level of detail and focus of the project. “It’s a total change in the culture from the 2016 guidelines,” he said, characterizing the earlier edition as ordering doctors to “just cut down on opioids — period.”By contrast, the new proposal “has a much more caring voice than a policing one, and it’s left room to preserve the physician-patient relationship,” added Dr. Narouze, chairman of the Center for Pain Medicine at Western Reserve Hospital in Cuyahoga Falls, OH.The 229-page document warns of addiction, depressed breathing, altered mental status and other dangers associated with opioids, but it also notes that the drugs serve an important medical purpose, especially for easing the immediate agony from traumatic injuries such as burns and crushed bones. In those instances when opioids seem the way to go, the recommendations said, doctors should start with the lowest effective dose and prescribe immediate-release pills rather than long-acting ones.The recommendations are now open on the Federal Register for public comment for 60 days. The agency will review the comments and most likely issue a final version by the end of 2022. Like the 2016 guidelines, they are suggested practices and not mandatory.“We are welcoming comments from patients who are living with pain every day and from their caregivers and providers,” said Christopher Jones, a co-author of the draft and acting director of the National Center for Injury Prevention and Control, the arm of the C.D.C. that released the new guidelines.Kate Nicholson, executive director of the National Pain Advocacy Center, a patient organization that says it does not take funding from the pharmaceutical industry, found much to admire in the new guidelines. “We went from one side of the pendulum, with overly liberal prescribing of opioids, and that did harm, to just looking at gross drops in prescribing without looking at individual needs. And that did harm,” said Ms. Nicholson, whose input was sought during the development of the draft. “This is closer to a Goldilocks solution where chronic pain is not a monolith.”The guidelines do not apply to patients suffering pain from cancer or sickle cell, or are in end-of-life or palliative care. Ms. Nicholson said, however, that relying on such disease categories — which insurance companies seize upon to make reimbursement rulings — “doesn’t tell us enough about who actually has severe pain.”The 2016 guidelines generated anger and fear in many chronic pain patients, many of whom rely on doses far higher than the recommended ceiling of 90 morphine milligram equivalents daily. Hundreds of pain medicine specialists protested as well.Though the dosing ceilings were merely a recommendation, dozens of states codified them. Fearing criminal and civil penalties, many doctors misapplied them as rigid standards, tapering chronic pain patients too abruptly and even tossing some from their practices.Studies show that the number of opioid prescriptions overall has been dropping since 2012, and the decline escalated after the 2016 guidelines came out.The new proposed recommendations step back from the notion of one-size dosing fits all and instead builds in “flexibility to recognize that pain care needs to be individualized,” Dr. Jones said.But the recommendations make it abundantly clear that doctors should regularly reassess the benefits and risks of opioids.“The evidence around the long-term benefits of opioids continues to remain very limited,” Dr. Jones said.In another indication that the C.D.C. sees these new guidelines as a course-correction to the earlier ones, the agency now suggests that when patients test positive for illicit substances, doctors should offer counseling, treatment and, when necessary, careful tapering. Because doctors had interpreted the 2016 dosing limits narrowly, some had worked up one-strike policies and were summarily ejecting such patients.Dr. Jones said that such results should instead be considered one piece of diagnostic information among many. An unduly high level of opioids could indicate the patient still has untreated pain or even a substance use disorder. “If you instead retain the patient and have those conversations, there’s now an opportunity to improve the patient’s life,” he said.Drawing from a mountain of research that accumulated in recent years, the proposed guidelines also offer extensive recommendations for the treatment of acute pain — short-term pain that can come with an injury like a broken bone or the aftermath of surgery. They advise against prescribing opioids, except for traumatic injuries, such as burns and auto accidents.In granular detail, they compare the relief provided by opioids to that offered by alternatives such as exercise and acupuncture and other drugs. And they give fine-tuned recommendations for discrete areas of pain, such as lower back, knees and neck.The guidelines, for example, note that opioids should not be used for episodic migraines. They endorse, among other treatments, heat therapy and weight loss for knee osteoarthritis, and, for neck pain, suggest options like yoga, tai chi, qiqong, massage and acupuncture.Dr. Marie Hanna, an associate professor of anesthesia and critical care at Johns Hopkins University School of Medicine, said she was particularly enthusiastic about the depth and breadth of research that the guidelines provide in support of nonopioid treatments, including manual manipulation, laser therapy and exercise.“This is what we’ve been talking about for years, but no one was listening. Now we have the evidence to show that these treatments are effective. I’m very optimistic,” added Dr. Hanna, a member of the American Academy of Pain Medicine, an organization of pain researchers and providers across several disciplines.The recommendations also say that many studies show that, over time, pain alleviation from opioids usually plateaus and then wanes, requiring ever higher doses.“We never wanted to pretend that opioids aren’t really important tools,” said Dr. Jeanmarie Perrone, a professor of emergency medicine at the Perelman School of Medicine at the University of Pennsylvania, who served on an advisory panel for the prescribing guidelines. “But after you’ve got that cast on, we’re going to wean you off those opioids. One long-bone fracture doesn’t mean six weeks of opioid prescriptions.”

People who find themselves alone after a significant knock to the head are at higher risk of harm.It appeared to be an ordinary fall: Bob Saget, the actor and comedian, knocked his head on something and, perhaps thinking nothing of it, went to sleep, his family said on Wednesday.But the chilling consequences — Mr. Saget, 65, died some hours later on Jan. 9 from blunt head trauma, a medical examiner ruled — have underscored the dangers of traumatic brain injuries, even those that do not initially seem to be causes for alarm.Some 61,000 deaths in 2019 were related to traumatic brain injuries, according to the Centers for Disease Control and Prevention, and nearly half of head trauma-related hospitalizations result from falls.Brain injury experts said on Thursday that Mr. Saget’s case was relatively uncommon: People with serious head trauma would be expected to have noticeable symptoms, like a headache, nausea or confusion. And they can generally be saved by surgeons opening up their skull and relieving pressure on the brain from bleeding.But certain situations put people at higher risk for the sort of deterioration that Mr. Saget experienced, doctors said.As serious a risk factor as any, doctors said, is simply being alone. Someone with a head injury can lose touch with their usual decision-making capacities and become confused, agitated or unusually sleepy. Those symptoms, in turn, can stand in the way of getting help.And while there was no indication that Mr. Saget was taking blood thinners, experts said the medications can greatly accelerate the type of bleeding after a head injury that forces the brain downward and compresses the centers that regulate breathing and other vital functions. More Americans are being prescribed these drugs as the population ages.Mr. Saget had been in an Orlando hotel room during a weekend of stand-up comedy acts when he was found unresponsive. The local medical examiner’s office announced on Wednesday that his death resulted from “blunt head trauma,” and said that “his injuries were most likely incurred from an unwitnessed fall.”There was no evidence of illegal drugs in his system, the medical examiner said.“If you have a head injury, you never — and I mean never — be by yourself for the first 24 hours,” said Dr. Gavin Britz, the chair in neurosurgery at Houston Methodist.Dr. Britz said that he would counsel people who get a significant knock to the head to see a doctor or, short of that, to ask someone to track their symptoms and even wake them up occasionally at night for monitoring.Brain injury experts also emphasized that the presence of symptoms usually indicated whether medical help was needed.“There’s no need to call the doctor after a little bump,” said Dr. Jeffrey Bazarian, an emergency physician and concussion expert at the University of Rochester Medical Center. On the other hand, he said, “If you hit your head and have lingering symptoms, like a headache or confusion, that requires medical attention — especially if you’re on a blood thinner.”The C.D.C. warns that traumatic brain injuries can be overlooked in older people when the symptoms overlap with those seen in other common ailments, like dementia.People 75 and older account for roughly one-third of head trauma-related hospitalizations, the agency said, though experts said they tend to apply extra caution to any patients who are at least 60 years old. C.D.C. data indicate that men are at higher risk than women.Neither Mr. Saget’s family nor the medical examiner offered details on Wednesday about precisely how the head injury had killed him.The family specified that Mr. Saget had accidentally hit the back of his head. Injuries to the sides and back of the skull may be associated with significant brain bleeding, said Dr. Angela Lumba-Brown, an associate professor of emergency medicine at Stanford University School of Medicine.Still, she said, significant blows to any part of the head can cause problems.Doctors said that there were a number of possible scenarios for how Mr. Saget died. They also cautioned that crucial details of his case were missing, like whether or not he had underlying conditions and the precise nature of his injuries.In one scenario, they said, more common among younger patients, someone receives a blow to the head serious enough that their skull fractures, rupturing a blood vessel or artery between the skull and the thick lining covering the brain. The result is an epidural hematoma, and the bleeding can be deadly. In some such cases, there is an interval when patients feel fine.That was the injury that killed the actress Natasha Richardson in 2009 after what appeared to be a minor fall on a beginner’s ski slope.“Maybe there’s a bit of a headache, and you go to bed, and the blood clot expands,” Dr. Britz said. “Over time, it gets so big that you get brain stem compression.”Another scenario is a fall that ruptures small veins between the membrane covering the brain and the brain itself, doctors said. That kind of injury is more common in older patients — a result, in part, of brains shrinking as people age, doctors said, and the prevalence of blood thinners.In those cases, known as subdural hematomas, symptoms can develop quickly or over the course of weeks.Brain experts said that as Americans age and, in many cases, go on blood thinners after a heart attack or stroke, the risks of head injuries become more pronounced.“As our population is aging, we have to be aware of the risks that come with being on blood thinners,” said Dr. Neha Dangayach, the director of neuroemergencies management for Mount Sinai Health System. “If you fall or hit your head, don’t write it off.”Still, doctors said, those head injuries were often easily treatable and deaths usually completely preventable.Dr. Jamshid Ghajar, a neurosurgeon at Stanford University School of Medicine who has worked on guidelines for treating brain injuries, said that he had operated on a 100-year-old with a serious head injury.“I took the blood out,” Dr. Ghajar said, “and he was awake right away after.”

President Biden came into office vowing to respect science, but openings in crucial jobs could hamper progress on medical and technological research.WASHINGTON — President Biden, who came into office vowing to “reinvigorate our national science and technology strategy,” is now facing a leadership vacuum that may threaten his ambitious research agenda, which stretches well beyond fighting the coronavirus pandemic.Both the Food and Drug Administration and the National Institutes of Health lack permanent leaders. Mr. Biden’s health secretary, Xavier Becerra, has been criticized for his low profile. And on Monday, his science adviser, Dr. Eric S. Lander — the first such adviser to serve in the cabinet — resigned after acknowledging that he had bullied his colleagues.Dr. Lander’s departure leaves a particularly big hole. He was in charge of the “cancer moonshot,” an initiative to cut death rates from cancer in half over the next 25 years, and was behind a new pandemic preparedness plan that the White House has likened to the Apollo mission.Dr. Lander was also a driving force behind Mr. Biden’s proposal to create a new agency to propel innovation in medical research. Modeled after the Defense Advanced Research Projects Agency, the proposed agency, known as ARPA-H, was the subject of a House committee hearing on Tuesday. Dr. Lander, who was supposed to be the key witness, was not there.Dr. Eric S. Lander resigned on Monday after acknowledging that he had bullied his colleagues.Oliver Contreras for The New York Times“This was an administration that really committed to the primacy of science for the pandemic and also aspirations for well beyond the pandemic,” said Dr. Eric Topol, the founder and director of the Scripps Research Translational Institute. “And what it has been on is a self-inflicting harm mission.”Administration officials say the work will carry on. Kevin Munoz, a White House spokesman, said the administration has “exceptional leadership” at the Department of Health and Human Services, and “strong acting leadership” at the F.D.A. and the health institutes.The F.D.A. is being run by an acting commissioner, Dr. Janet Woodcock, and Dr. Lawrence Tabak is the acting director of the N.I.H. after its longtime leader, Dr. Francis S. Collins, stepped down late last year. Both Dr. Woodcock and Dr. Tabak are longtime officials at their respective agencies, regarded as steady hands.But Sudip Parikh, the chief executive of the American Association for the Advancement of Science, said he was deeply concerned that, without permanent leaders, it would be difficult for federal agencies to carry out Mr. Biden’s agenda with imagination and vision.In addition to considering whether to create and fund ARPA-H, the House and the Senate are working to reconcile their versions of legislation authorizing an increase in funding for the National Science Foundation, which would expand research in a range of science and technology fields, like quantum computing and artificial intelligence.“I am excited about what we have accomplished so far, but I am really worried about this next set of steps,” Dr. Parikh said. “We are on the cusp of some of the biggest changes to the way we do science in this country in 74 years, so we want Senate-confirmed scientific leaders that can put forth a vision.”Ellen Sigal, the chairwoman and founder of Friends of Cancer Research, an advocacy group in Washington, shares that concern.“They promptly need to have an F.D.A. commissioner confirmed, they have to have an announcement on who will direct the N.I.H. and then they are going to have to replace Dr. Lander and figure out who has the stature to bring these various initiatives together,” she said.After the administration of former President Donald J. Trump, who routinely spread misinformation about the coronavirus, scientists were thrilled and relieved when Mr. Biden was elected.“Our long national nightmare is over,” R. Alta Charo, professor emerita of law and bioethics at the University of Wisconsin, told Scientific American at the time.In an interview on Thursday, Ms. Charo said Mr. Biden had fulfilled his pledge of respecting scientific integrity, and his response to the pandemic, while not perfect, had been a big improvement. Still, she said, “I think it’s appalling that we have such a vacuum of leadership.”Others have been less charitable. Holden Thorp, a former chancellor of the University of North Carolina at Chapel Hill who is now the editor in chief of Science, published an editorial on Tuesday calling Dr. Lander’s departure “the latest disappointment from an administration that has been struggling to guide the nation with sound science and science leadership.”Some critics of the administration say Mr. Biden brought some of the problems on himself with the people he chose to put in various leadership positions.The Coronavirus Pandemic: Key Things to KnowCard 1 of 3Some mask mandates ending.

The panel debated whether overseas trials could be applied to a more diverse U.S. population. The decision may affect other Chinese drug trials, and spotlights the high cost of immunotherapy.An advisory committee to the Food and Drug Administration overwhelmingly voted on Thursday against recommending agency approval of a lung cancer drug that was tested only in China and sold there.The drug, sintilimab, is a checkpoint inhibitor — a type of immunotherapy drug that unleashes the immune system to attack tumors. It was developed and tested in China by Innovent Biologics, which entered into an agreement with Eli Lilly that would have allowed Lilly to market it in the United States, if it were approved. It was to be used in combination with chemotherapy for patients with metastatic non-small-cell lung cancer.The F.D.A. panel debated a longstanding issue: What standards should be used in approving drugs? Should a drug tested only in China or another country outside the United States be accepted without domestic trials?The decision is likely to be closely monitored for clues about whether it further exacerbates tensions between the United States and China, especially given the strains between the two countries over research by Chinese scientists in recent years. Immunotherapy drugs are so expensive in the United States that the potential to bring a cheaper therapy to the market also weighed heavily in the background of the discussion on Thursday.Dr. Richard Pazdur, the powerful director of the F.D.A.’s oncology unit, explained on Thursday why he had backtracked from a far more welcoming attitude in 2019, when he said the agency might consider a checkpoint inhibitor tested solely in China.“Over the past two or three years, this country has experienced tremendous social change,” he said at the meeting. “We clearly heard from all patient groups that they want faces like theirs.” That, he said, is also important to build confidence in the clinical trials and the drugs being tested.A drug tested only in China is “a step backward,” he said.The agency has faced considerable pressure to include diverse patient groups, reflecting various ethnic and racial populations, in clinical trials in the United States as well as to address health disparities.Lilly released a statement saying that it was disappointed and that it had “hoped that sintilimab could have played a positive role for patients and the U.S. health care system through an aggressive pricing strategy.”But, the company said that “we acknowledge that the landscape has changed dramatically” and that Lilly “wholeheartedly agrees with the importance of ethics in clinical trial conduct and clinical trial diversity.”The company said it “will be working with FDA on next steps.”Another issue surrounded Lilly’s decision to even submit this drug for U.S. approval. An analysis by the F.D.A.’s staff of the trial results in China was scathing on methodological grounds. It cited a failure to provide patients in the control group with an approved therapy that is standard of care; questioned the competence of some of the investigators who had no previous experience with such trials; noted a patient population that was younger, had more men, and had fewer smokers than U.S. lung cancer patients; and criticized use of an endpoint that is considered not always reliable.Lilly had promoted its application by saying that it wanted to use sintilimab as a wedge to break the stratospheric prices of cancer immunotherapy.Already on the market are several other checkpoint inhibitors, which make cancers vulnerable by blocking a protein that tumors use as sort of an invisible shield to protect them from an immune system attack. These immunotherapy drugs treat such cancers as colon, breast, liver and lung, and carry list prices that are nearly identical — about $150,000 a year per patient.Lilly said it would charge 40 percent less if its drug were approved. Sintilimab costs $6,000 a year in China.The company’s idea of breaking the price lock on such drugs is “a big deal,” Brad Loncar, a biotechnology industry investor, said.“I’m not aware of any precedent of a company, especially of Lilly’s size and credibility, announcing that a discounted price like this is how they planned to innovate,” Mr. Loncar said.Now, he added, the near certainty that the drug application would be rejected “means that a real option for substantially lower drug prices is being closed in the U.S.” (The F.D.A. generally follows the recommendations of its advisory committees.)Others were not persuaded by Lilly’s claim to be a market disrupter.If approved, the drug would have been marketed in the U.S. by Eli Lilly and used in combination with chemotherapy for patients with metastatic non-small-cell lung cancer.Mike Segar/ReutersDr. Scott Ramsey, a health economist and cancer specialist at Fred Hutchinson Cancer Center in Seattle, was among those who were skeptical of Lilly’s motives. “Yeah, right,” he commented.“Are they talking about the stranglehold on prices that their current drugs contribute to?” Dr. Ramsey asked. “Maybe they could start by knocking 40 percent off their price” for Cyramza — a stomach cancer drug with a list price of $13,400.32 to $15,075.36 per month — and Verzenio, a breast cancer drug with a similar price.“I don’t buy it,” Dr. Ramsey said of Lilly’s price disrupter story, and instead chalked it up to a public relations stunt.It is well known that the F.D.A. is not permitted to consider price in evaluating whether a drug should be approved. That means that any F.D.A. decision must be based solely on whether the drug meets its standards.For that reason, Dr. Aaron Kesselheim, a professor of medicine at the Harvard T.H. Chan School of Public Health and an expert on the pharmaceutical industry, was puzzled.“I’m not aware of a company ever before announcing its pricing strategy just before an AdComm meeting, particularly one in which the general perception is that the F.D.A. was going to argue that the data don’t seem to support approval,” he said, referring to the agency’s advisory committee panel. “It does seem like a strategic ploy intended to inject a consideration into the AdComm deliberations that is not supposed to be considered.”The story of sintilimab dates to 2019 at the annual meeting of the American Association of Cancer Research. Speaking there, Dr. Pazdur said the agency would be open to considering drugs tested solely in other countries.Lilly, which had said it had not planned to market sintilimab outside China, said at the meeting that it then decided to see if the drug could be approved in the United States. The company met with the agency three times in 2020 and proceeded to apply for marketing approval.New Developments in Cancer ResearchCard 1 of 6Progress in the field.