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Big data, Emergency Medicine, Genetics, Infectious Disease, Research, Stanford News

Study means an early, accurate, life-saving sepsis diagnosis could be coming soon

Study means an early, accurate, life-saving sepsis diagnosis could be coming soon

image.img.320.highA blood test for quickly and accurately detecting sepsis, a deadly immune-system panic attack set off when our body wildly overreacts to the presence of infectious pathogens, may soon be at hand.

Sepsis is the leading cause of hospital deaths in the United States and is tied to the early deaths of at least 750,000 Americans each year. Usually caused by bacterial rather than viral infections, this intense, dangerous and rapidly progressing whole-body inflammatory syndrome is best treated with antibiotics.

The trouble is, sepsis is exceedingly difficult to distinguish from its non-infectious doppelganger: an outwardly similar but pathogen-free systemic syndrome called sterile inflammation, which can arise in response to traumatic injuries, surgery, blood clots or other noninfectious causes.

In a recent news release, I wrote:

[H]ospital clinicians are pressured to treat anybody showing signs of systemic inflammation with antibiotics. That can encourage bacterial drug resistance and, by killing off harmless bacteria in the gut, lead to colonization by pathogenic bacteria, such as Clostridium difficile.

Not ideal. When a patient has a sterile inflammation, antibiotics not only don’t help but are counterproductive. However, the occasion for my news release was the identification, by Stanford biomedical informatics wizard Purvesh Khatri, PhD, and his colleagues, of a tiny set of genes that act differently under the onslaught of sepsis from they way they behave when a patient is undergoing sterile inflammation instead.

In a study published in Science Translational Medicine, Khatri’s team pulled a needle out of a haystack – activity levels of more than 80 percent of all of a person’s genes change markedly, and in a chaotically fluctuating manner over time, in response to both sepsis and sterile inflammation. To cut through the chaos, the investigators applied some clever analytical logic to a “big data” search of gene-activity results on more than 2,900 blood samples from nearly 1,600 patients in 27 different data sets containing medical information on diverse patient groups: men and women, young and old, some suffering from sterile inflammation and other experiencing sepsis,  and (as a control) healthy people.

The needle that emerged from that 20,000-gene-strong haystack of haywire fluctuations in gene activity consisted of an 11-gene “signature” that, Khatri thinks, could serve up a speedy, sensitive, and specific diagnosis of sepsis in the form of a simple blood test.

The 11-gene blood test still has to be validated by independent researchers, licensed to manufacturers, and approved by the FDA. Let’s hope for smooth sailing. Every hour saved in figuring out a possible sepsis sufferer’s actual condition represents, potentially, thousands of lives saved annually in the United States alone, not to mention billions of dollars in savings to the U.S. health-care system.

Previously: Extracting signal from noise to combat organ rejection and Can battling sepsis in a game improve the odds for material world wins?
Photo by Lightspring/Shutterstock

Emergency Medicine, Global Health, Stanford News

“Still many unknowns”: Stanford physician reflects on post-earthquake Nepal

"Still many unknowns": Stanford physician reflects on post-earthquake Nepal

Paul Auerbach recently traveled to Nepal to aid victims of the April 25 earthquake; he wrote this post over the weekend.

17313678335_5f5d15dc04_zI’m on my way back to the U.S. now and getting information from people who are still in Nepal. Because I’m inundated with requests to provide information from people who have read my previous posts, I’ll keep writing, but only if there’s something useful to report. Please let me emphasize that this is no longer firsthand, but rather, based on communications from persons in Nepal whom I very much trust. They are working really hard, so it is “above and beyond” (and very much appreciated) that they find time to keep us all informed.

Surrounding Kathmandu and seen from the air, there are many remote villages that have been devastated, with all or nearly all dwellings demolished by the earthquake. These buildings had mostly been constructed of bricks mortared with mud. They crumbled during the shaking and may have been struck by rock slides. Anyone caught within the buildings could have been mortally wounded or severely injured.

Many villages are situated one or more days’ walk from the nearest vehicle (4-wheel drive truck or SUV)-accessible roadway, so rapid access will need to be by helicopter if there is a suitable landing site or the ability to carry out long-line rescues (this requires the appropriate equipment and operators with technical expertise, both on the ground and in the helicopter). Helicopters are in short supply relative to the need, so that is a rate-limiting part of the operation. The helicopters will be needed both to get teams in and to get patients out. The first step will be to provide on-site triage in order to prioritize where to deploy medical and other resources. Patients will be assessed in order to determine whom to transport and in what order. Treatment will be initiated when possible. The possibility of trekking into villages will be dictated by the condition of the paths normally used for foot travel. The paths are often narrow, rocky, and steep. It is likely that there have been rock-and-dirt slides that will render traversing some of these paths extremely difficult or impossible. If the paths are passable, that may be how some of these villages will eventually be reached, and people and supplies delivered. The delays will be overcome by cooperation and perseverance.

Medical teams from around the globe have come into Kathmandu and are assisting or prepared to assist. They will be responsive to the Nepal government, global-health agencies such as the World Health Organization, and non-governmental organizations such as International Medical Corps. The search and rescue (SAR) component intended to find victims trapped in rubble will expect from this point forward to find only a few miraculous survivors of the initial event, so the role of SAR to extricate buried people will diminish. From this point forward, it will be about getting to the injured and sustaining them until they can be extracted to a higher level of medical care, if this is what they need. Reaching all the affected villages and injured persons may take weeks. To assist displaced (e.g., no longer have a home) persons, there is need to provide food, sheltering materials, and water disinfection supplies.

The public-health mission, in particular trying to prevent the spread of potentially epidemic infectious disease (particularly diarrheal disease) is hugely important. This is essential now and particularly as the monsoon season approaches. This includes human-waste management, providing safe drinking water, possibly providing immunizations, and surveillance that promotes early detection of disease.

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Emergency Medicine, Global Health, Stanford News

Day 6: Heading for home after treating Nepal earthquake victims

Day 6: Heading for home after treating Nepal earthquake victims

Paul Auerbach has been in Nepal to aid victims of the recent earthquake; he wrote this account over the weekend.

Nepal earthquake2 - smallThe last few days have been action-packed, and my work in Nepal is coming to a close. As an emergency physician, my skills will soon be much less needed than those of orthopedic and plastic surgeons, and primary care and infectious disease specialists. Because of the incredible outpouring of active interest from people who are friends of Nepal, many health-care professionals have arrived, and more are on the way. The government of Nepal has recommended that all persons, particularly those in large groups or teams, wishing to help by coming to Nepal do so under the auspices of a government-approved organization. This is important to maintain an effective response and deploy resources where they are most needed.

It has been a bit unnerving to experience three significant aftershocks over the past few days. Each was accompanied by a jolt or shaking of the ground or building and rumbling noise, followed by silence, followed by the sounds of commotion as people fled their dwellings. Fortunately, none of the aftershocks was prolonged or destructive, but they serve as a reminder of what happened, and what will undoubtedly happen again sometime in the future. The cycle for a major earthquake in this country in modern times is approximately every 75 years.

Today we traveled to Hatia, a community close to Dhading, in order to assess need and provide care. We were greeted by approximately 100 residents with earthquake-related situations, illnesses, and injuries. Nearly all of them are now displaced from their homes. With the monsoon on the horizon beginning the end of this month or early in June, combined with the number of persons requiring new shelter, the timetable is set for an aggressive attempt to provide adequate housing, essential public health education, and water-sanitation-hygiene (WASH) programs. More victims of the earthquake will undoubtedly be found as helicopters are deployed to approach very difficult-to-reach areas, so there will continue to be an immediate medical response as long as the public health efforts.

I have witnessed many acts of selflessness and heard tales of amazing bravery, including what transpired at Everest Base Camp. The details of everything that has happened in this country related to the earthquake will be best told by those who experienced it first-hand. From a personal perspective, I’m impressed by the number of participants in the events and response that has come from the wilderness medicine community. These are some of my dearest friends and colleagues, and my admiration for them has grown by leaps and bounds. Working with my lifelong friend Luanne Freer, MD, has been a privilege. Her knowledge of Nepal and love for the country permeated everything she did this past week. There are many people like her who have come to help, and behind every person here there are dozens at home supporting their efforts.

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Emergency Medicine, Global Health, Stanford News

Day 4: Reaching beyond Kathmandu in treating Nepal earthquake victims

Day 4: Reaching beyond Kathmandu in treating Nepal earthquake victims

Paul Auerbach is in Nepal to aid victims of the recent earthquake and has been sending periodic reports.

The earthquake in Nepal caused immense damage to people and property not only in Kathmandu, but in a widespread area extending to Mt. Everest and in many other directions. Victims on Mt. Everest and in Kathmandu proper appropriately received a great deal of attention, but equally important has been the plight of persons trapped in villages remote from the big city. These communities are located in steep and isolated terrain, so that it is difficult to reach them by road, and sometimes even by helicopter. Part of the mission of International Medical Corps (IMC) and the other responding organizations has been to identify these areas of need and attempt to locate and treat the victims.

We continue to see improvement each day, and the number of volunteers from around the world is impressive

After a discussion with three health officials – the senior district health officer for Dhading, a pediatrician assigned to lead the district medical response to the earthquake, and the medical supervisor for the Dharding District Hospital, we were asked to consider finding a way to approach one of several villages that were reported to have urgent medical needs, but which had not yet been visited by rescuers and medical professionals. We selected Kumpur, a rugged 90-minute approach requiring a 4-wheel drive vehicle. We excluded others that required helicopter access, because these aircraft have been in short supply.

At the Dhading District Hospital, we witnessed arrival of a dozen earthquake victims choppered in from Darkha, which is at a high elevation in this region. They were suffering from trauma, with broken limbs and wounds in various stages of infection. The Nepalese doctors who volunteered their time by leaving Bangladesh to respond at the request of IMC, alongside a (literally) busload of surgeons and other medical professionals volunteering from India were skilled and swift in delivering treatment despite the limited resources and surge of patients.

The next day, we took a team into Kumpur and witnessed widespread destruction amid the beautiful surroundings. Many dwellings composed of mud and stone had collapsed, and the residents are now living in tents. With the monsoon season approaching, they will need assistance to rapidly create more suitable structures. They were busy clearing the remains of their homes and other structures, but always gave us a smile and a greeting. Their resilience and work ethic are amazing.

The health outpost has been rendered largely unusable, with large cracks in its side, holes in the wall, and instability in every direction. So, we worked mostly in the single safe room remaining and on the porch leading to the entryway. With a stellar support team, including two recently graduated doctors from Nepal, we were able to interview and examine many of the villagers, dealing with complaints both related to injuries sustained in the earthquake and medical conditions for which they sought advice.

As the days pass, fewer patients will present with acute earthquake-related injuries, and the medical care will shift to resumption of adequate primary care, surgeries related to orthopedic and soft tissue injuries, and aggressive detection and management of infectious diseases that might cause an epidemic. Public-health experts are on-scene, as are epidemiologists and other experts in sanitation systems, water disinfection, and so forth. Given the large geographic area affected by the earthquake and difficulty reaching many locations, the logistics are extremely important.

We continue to see improvement each day, and the number of volunteers from around the world is impressive. We hope for the best and appreciate all the support we’ve received from family and friends.

Paul Auerbach, MD, is a professor and chief of emergency medicine who works with the Stanford Emergency Medicine Program for Emergency Response (SEMPER).

Click here for a statement on Nepal from Michele Barry, MD, senior associate dean of global health and director of the Center for Innovation in Global Health (CIGH). Additional updates related to the Stanford relief efforts will be shared on the CIGH website in the coming days and weeks.

Previously: Day 2: “We have heard tales of miraculous survival” following Nepal earthquake and Day 1: Arriving in Nepal to aid earthquake victims

Emergency Medicine, Global Health, Stanford News

Day 2: “We have heard tales of miraculous survival” following Nepal earthquake

Day 2: "We have heard tales of miraculous survival" following Nepal earthquake

Paul Auerbach is in Nepal to aid victims of the recent earthquake and has been sending periodic reports.

Today in Kathmandu was quite different from yesterday. The city has certainly sprung back remarkably. Although its citizens face enormous challenges, the streets were nearly full with traffic, rubble was actively being cleared from obstructing piles, and people were walking and resuming commerce. There are an estimated 16 camps within the boundaries of Kathmandu, where people are either forced to seek housing or prefer to remain, certainly for sleeping at night, until homes can be replaced or cleared with respect to structural integrity. The camps are orderly and treated with dignity by the occupants and passers-by. We visited one this afternoon to perform a clinic, examining patients who wished to see a physician. Because the hospitals in Kathmandu received the injured soon after the earthquake, we mostly served persons with “routine” medical ailments. They were kind to us and appreciated the attention.

International Medical Corps continues to grow its staff and operations to meet the evolving situation. Side by side with other entities that have responded, including large national emergency response teams, there will be increasing focus on the communities outside Kathmandu, where there is sparse medical care and distances to hospitals mean walks of hours. Some of these will need to be approached by helicopter because of distances, mud- and rockslides caused by the earthquakes that have obstructed roadways, and calls for urgent assistance. It’s anticipated that some teams may need to trek for days to reach certain villages. Much of the coming days’ and weeks’ activities will be intended to avoid the spread of infectious diseases.

We have heard tales of miraculous survival, sadly posed against the grief of many lost family members and friends. Driving through the city past enormous mounds of rubble that last week were sacred temples and monuments, it is striking to think about how much there is to be done worldwide to prepare for cataclysmic natural events. There will be many lessons learned from this catastrophe, and we should take them to heart. One of them is how much better is a world focused on mutual aid and skillful compassion than upon dominance and conflict.

Paul Auerbach, MD, is a professor and chief of emergency medicine who works with the Stanford Emergency Medicine Program for Emergency Response (SEMPER).

Click here for a statement on Nepal from Michele Barry, MD, senior associate dean of global health and director of the Center for Innovation in Global Health (CIGH). Additional updates related to the Stanford relief efforts will be shared on the CIGH website in the coming days and weeks.

Previously: Day 1: Arriving in Nepal to aid earthquake victims

Emergency Medicine, Global Health, Stanford News

Day 1: Arriving in Nepal to aid earthquake victims

Day 1: Arriving in Nepal to aid earthquake victims

17290207611_0062388d65_zUnder the auspices of International Medical Corps, I’ve just joined a team that will be growing to help meet the needs of Nepal following the recent devastating earthquake. It wasn’t easy to fly in, because the airport has a single main runway and isn’t large enough to park many large aircraft, and there is a great number of relief flights from all around the globe bringing people, equipment, and supplies. Our commercial flight was largely occupied by responders, including an official Japanese search and rescue team, as well as concerned and courageous people of Nepal returning to be with their families. Yesterday our plane originated out of Bangkok, was diverted twice to India, and then returned to Bangkok. We were fortunate to get an early start today and reach Kathmandu.

The scene is somewhat reminiscent of what we encountered five years ago in Haiti, with the main exception being that there is much more of a structured health-care system in Nepal than there was in Haiti, and so the national medical response has been significantly more robust. Still, there are more than 4,000 known victims, and likely many more to be discovered in areas surrounding Kathmandu that are difficult to reach. Furthermore, there will be at least quadruple that number of persons with significant injuries.

Having been to Kathmandu a few times on my way to the majestic Himalaya mountains to trek, including to Everest Base Camp (which was struck by a devastating avalanche caused by the earthquake), it was very sad to see the collapse of buildings – indeed large portions of certain neighborhoods – as well as ancient temples and iconic structures. Soon after leaving the airport, I witnessed resilient citizens sheltering under tents because their homes are destroyed or structurally unstable endure a fierce rainstorm with sheets of hail, causing some streets to flood and emphasizing the risk for spread of infectious disease, such as cholera, in the aftermath of the earthquake.

The local medical community has responded aggressively to this situation, and the health professionals have been working around the clock to tend to patients. The overall community led by volunteers is assessing its capabilities to support shelter, hygiene, provision of safe water and food, and integration of its capabilities with those that are coming in relief. The government is working hard to integrate its efforts with non-governmental agencies, other countries, and generous donors of all necessary aspects of the much needed relief effort.

Please keep the people of Nepal in your thoughts and prayers.

Paul Auerbach, MD, is a professor and chief of emergency medicine who works with the Stanford Emergency Medicine Program for Emergency Response (SEMPER).

Click here for a statement on Nepal from Michele Barry, MD, senior associate dean of global health and director of the Center for Innovation in Global Health (CIGH). Additional updates related to the Stanford relief efforts will be shared on the CIGH website in the coming days and weeks.

Previously: Stanford emergency-response team heads to the Philippines, Treating the injured amid the apocalypse of Haiti, Reports from Stanford medical team in Haiti and Stanford sends medical team to Haiti
Related: Stanford’s SEMPER team provides relief to Typhoon Haiyan survivors and Report from Haiti: ‘None of us had ever seen anything like it’
Photo by Domenico

Emergency Medicine, Medicine and Society, Public Health, Public Safety, Research

Study: ER statistics could be used to help reduce gun violence

Study: ER statistics could be used to help reduce gun violence

ER shot

Emergency room doctors treat many patients who have been involved in violent assaults. New research shows that these patients are far more likely than other ER patients with otherwise similar demographics to seek treatment for gun-related injuries in the near future.

These findings “could help injury researchers, emergency department physicians, and social service agencies focus their intervention efforts to prevent future firearm incidents and other violent incidents among high-risk youth populations,” explains a University of Michigan press release published Monday.

The study, published in Pediatrics, followed nearly 600 drug-using youth in Flint, Mich. for two years after they were admitted to the emergency room. Nearly 60 percent of those admitted for assault-injury care became involved in a violent incident involving a firearm within the next two years, and of those, the majority did so within six months after the initial visit. Between two people with highly similar demographic factors, someone admitted for assault is 40 percent more likely to be involved in gun violence than someone admitted for a cold.

The results also calculated the statistical correlations of various markers, such as race, gender, drug abuse, PTSD, possession of a firearm, and tendency toward retaliation (see the release for the details). ERs that track such markers could identify the highest-risk youth and help them receive targeted treatment. The release quotes Patrick M. Carter, MD, an assistant professor of emergency medicine at UM, member of the UM Injury Center, and first author of the study, saying the results “support using the ER as the site for intervention, especially during the ‘teachable moment’ that immediately follows an initial assault or fight.”

Previously: Pediatricians’ role in gun control: Recommendations from the American Academy of Pediatrics, Emergency-room interventions may reduce alcohol-based violence among teens and Emergency room as soup kitchen
Photo by Military Health

Emergency Medicine, Health Costs, In the News, Research, Stanford News

Thinking twice before doing blood transfusions improves outcomes, reduces costs

Thinking twice before doing blood transfusions improves outcomes, reduces costs

7413610060_317879301e_zStanford Hospital has figured out that doing fewer blood transfusions saves lives – and millions of dollars annually. In two studies headed by Stanford’s Lawrence Goodnough, MD, professor of pathology and hematology, doctors were gently nudged by a computer program to think twice before performing a blood transfusion. The impressive results were discussed in a Nature news feature published Tuesday:

The number of red-blood-cell transfusions dropped by 24% between 2009 and 2013, representing an annual savings of $1.6 million in purchasing costs alone. And as transfusion rates fell, so did mortality, average length of stay and the number patients who needed to be readmitted within 30 days of a transfusion. By simply asking doctors to think twice about transfusions, the hospital had not only reduced costs, but also improved patient outcomes.

Transfusions are common procedures in industrialized countries, but scientists are finding that they’re overused. More research needs to be done to determine when, exactly, transfusions cross the line between helpful and harmful. They do save lives, but probably only for the most critically ill patients.

Decades of established practice and protocol are hard to change, though. Clinicians acting in the moment refer to their experience, not to guidelines. That’s one reason Stanford’s simple computer innovation is so important. Goodnough, quoted in Nature, speculates about why it succeeded: Not only did alerts remind doctors about the guidelines and provide links to the relevant literature, they forced them to slow down and think instead of running with the default. The alerts may have provided an opening for more individualized discussion among caregivers:

‘Maybe the intern, who was ordering the blood because they were told to, goes back to the team and says, “I have to give a reason”, and then they discuss it,’ Goodnough says. The clinicians might decide to order the blood anyway, of course. Or they might stop, consider the evidence, and come to agree with what Goodnough believes is its clear message. ‘The safest blood transfusion,’ he says, ‘is the one not given.’

Check out the article for more on the history of blood transfusions, other research into their optimal use, and new practices being pioneered around the world.

Previously: Fewer transfusions means better patient outcomes, lower mortality, Stanford Hospital trims use of blood supplies, Stanford test a landmark in the blood banking industry and Should the US create a national blood transfusion reporting system?
Related: Against the flow: What’s behind the decline in blood transfusions?
Photo by Banc de Sang i Teixits

Emergency Medicine, Medicine and Society, Patient Care, Public Safety, Stanford News

A young child, a falling cabinet, and a Life Flight rescue

A young child, a falling cabinet, and a Life Flight rescue

ticktockLife in the air rescue business is highly unpredictable. You can spend many hours idling away the time in an obscure, basement office. But when an emergency call comes, you literally don’t have a second to grab a pen on the way out the door.

So it was on one November day, when I did a ride-along with Stanford’s illustrious Life Flight air ambulance service, the oldest in California. The team graciously agreed to let me accompany them on a flight for a story for Stanford Medicine magazine, whose current issue is focused on the role of time in medicine. Life Flight, I figured, would give me a sense of the split-second timing that can sometimes make a difference between life and death in an emergency situation. I was scheduled to fly with the crew in late October, but instead I spent that day learning about the service in what proved to be a leisurely day with no calls.

On my second ride-along day, it appeared that history was about to repeat itself when, just as my shift was about to end, the emergency call came in at 3:39 p.m. I became an eye witness to the rescue of a toddler who suffered a serious head injury when a heavy, ill-secured cabinet at her preschool crashed down on her head during naptime. The story was so dramatic that it made the local news. The school was shut down several days later by local officials because of code violations.

Things could have gone poorly for little Aeshna, the 3-year-old victim of the accident, who was left dazed, not fully conscious and vomiting as a result of her injury – clear signs of head trauma. She could have suffered significant bleeding in the brain and permanent brain damage – a prospect that was a major concern for her parents and caregivers.

The two Life Flight nurses, who have a breathtaking array of skills, and their veteran U.S. Navy pilot made it to the scene at the Fremont, Ca. preschool across the bay within 23 minutes of the call and were able to bring Aeshna back to Stanford for quick assessment and treatment.

You can read the minute-by-minute scenario of Aeshna’s rescue in the the magazine, which came out last week.

Previously: Stanford Medicine magazine reports on time’s intersection with health, Comparing the cost-effectiveness of helicopter transport and ambulances for trauma victims, Stanford Life Flight celebrates 30 years and Ask Stanford Med: Answers to your questions about wildnerness medicine
Illustration by Lincoln Agnew

Aging, Cancer, Emergency Medicine, Medical Education, Pregnancy, Stanford News

Stanford Medicine magazine reports on time’s intersection with health

Stanford Medicine magazine reports on time's intersection with health

Why is it that giant tortoises typically live for 100 years but humans in the United States are lucky to make it past 80? And why does the life of an African killifish zip past in a matter of months?

I’ve often mused about the variability of life spans and I figure pretty much everyone else has too. But while editing the new issue of Stanford Medicine magazine’s special report on time and health, “Life time: The long and short of it,” I learned that serious scientists believe the limits are not set in stone.

“Ways of prolonging human life span are now within the realm of possibility,” says professor of genetics Anne Brunet, PhD, in “The Time of Your Life,” an article on the science of life spans. My first thought was, wow! Then I wondered if some day humans could live like the “immortal jellyfish,” which reverts back to its polyp state, matures and reverts again, ad infinitum. Now that would be interesting.

Also covered in the issue:

  • “Hacking the Biological Clock”: An article on attempts to co-opt the body’s timekeepers to treat cancer, ease jetlag and reverse learning disabilities.
  • “Time Lines”: A Q&A with bestselling author and physician Abraham Verghese, MD, on the timeless rituals of medicine. (The digital edition includes audio of an interview with Verghese.)
  • “Tick Tock”: A blow-by-blow account of the air-ambulance rescue of an injured toddler.
  • “Before I Go”: An essay about the nature of time from a young neurosurgeon who is now living with an advanced form of lung cancer. (The neurosurgeon, Paul Kalanithi, MD, is featured in the video above, and our digital edition also includes audio of an interview with him.)

The issue also includes a story about the danger-fraught birth of an unusual set of triplets and an excerpt from the new biography of Nobel Prize-winning Stanford biochemist Paul Berg, PhD, describing the sticky situation he found himself in graduate school.

Previously Stanford Medicine magazine traverses the immune system, Stanford Medicine magazine opens up the world of surgery and Mysteries of the heart: Stanford Medicine magazine answers cardiovascular questions.

Stanford Medicine Resources: