Novel biomedicalstudyseeksparticipants Novel the StateofStanford Medicine eventattheLiKaShingCenter. Lloyd Minor, David Entwistle andChristopherDawesspoke Oct.24 at vide thefirstcomprehensive atlasofwhat they remain healthyorfallill,couldpro- changes over time,regardless ofwhether study. ter aligntheprioritiesofmedicalschool,Stanford grated strategicplanningprocess, whichaimstobet- Packard Children’s Hospital Stanford, andtheinte- including theplannedopeningofexpandedLucile cal center’s three facilities, leadersalsohighlightednew nated the State of Stanford Medicine on Oct. 24. politics ofhealthcare were amongthetopicsthatdomi - Volume 9, No. 20 No.20 Volume 9, By RuthannRichter highlighted atStateofStanfordMedicine New children’s hospital, ProjectBaseline L By KristaConger enrolled its100 four years. Stanford Medicine recently overparticipants thecourseofatleast biomedical datafrom asmany10,000 repeatedly collectingvast amountsof stand themolecularbasisofhealthby School ofMedicine, itaimstounder- Medicine andtheDuke University company, withStanford inpartnership ing andplanningby Verily, anAlphabet Launched inApril afteryears ofdesign- with apotentially transformative payoff. world.” easy waytodosomethinggoodforthe been attempted,andIthinkit’s apretty wellness onascalethat’s never before to help informopportunity health and profit Rotaplast International. “It’s an three whovolunteers withthenon- 41, aformerphysicianandmotherof the humanbodywork,” saidPurchase, to understand more about what makes chance to participate. health anddisease—shejumpedatthe understand the basic underpinnings of largest, mostcomprehensive to efforts Project Baseline study—oneofthe Observing howObserving aperson’s healthdata During thelunchtimetown hallmeeting,themedi- ofThe a diverse importance community and the The studyisanambitiousendeavor, “I’m so excited of this effort tobe part spring, whensheheard aboutthe as kindofadatadevotee. So last eslie Purchase describes herself INSIDE STANFORD MEDICINE th participant inthe participant November 6, 2017 6, November disorders. stages ofcancer, diseaseorother heart nals given offby thebodyatearliest or helpresearchers learnthesubtlesig- it meanstobe“well” atallstagesoflife, Leslie Purchase ofMill Valley was amongthefirsttoenrollinStanford’s portionofProjectBaseline. The watch onherwristhelpskeep track ofheractivity. ROD SEARCEY PublishedbytheOfficeofCommunication&PublicAffairs dents are comprised of doctoral students inthebiosciencesand medicalstu- versity and inclusion and the search for solutions. health, are helpingtoshinealightonthe issuesofdi- conference inthe springonrace,policingandpublic and recent Stanford-sponsored meetings,includinga sentation andEmpowerment, atLaneMedical Library, ties. establishedDiversityThe newly Center of Repre- and inclusion remain one of the school’s high priori - campus community, sayingthat broad representation and prevent disease.” determinants of disease, and therefore be able to predict understand thedeterminantsofhealth,aswell asthe power inprecision anddrive ourefforts health—to was held. “We’re really hoping the conclusions will em- Center forLearningandKnowledge, where theevent nor toldsome350facultyandstaffattheLiKaShing tion about the predisposing factors for diseases,” Mi- abovenext four years (see story ). including5,000intheBayparticipants, Area, over the amounts ofbiomedicaldatafrom asmany10,000 stand themolecularbasisofhealthby collectingvast and Verily, anAlphabetcompany, thataimstounder- Project Baseline, withDuke apartnership University tives atthe school,includingStanford’s in participation kicked off the event by introducing several initia new Health Care and Stanford Children’s Health. This year, 25percent ofthe entering classesofboth Minor ofadiverse alsoemphasized theimportance “We shouldbeableforthefirsttimetogetinforma- Lloyd Minor, MD,deanoftheSchoolMedicine, and provide preemptive medicalcare to proactively monitoraperson’s health cine ispracticedby enabling physicians tential toeventually changehow medi- The scope of the effort, anditspo- The scopeoftheeffort, See MEDICINE, page6 - of marijuanause and thefrequency ofsexual intercourse. Researchers have foundapositiveassociationbetween thefrequency unambiguous. more than50,000 Americansages25-45.Andthey’re nal ofSexual Medicine, are basedonananalysisof to be the case. desire theoppositeappearsmore orperformance, likely scientists thatfrequent marijuanausemayimpairsexual indicates that,despiteconcernsamongphysiciansand confirmed. tweenmarijuana, has been sex and at leastonedrug, By BruceGoldman according tonewstudy linked tomore sex, Regular marijuanause The findings, published online Oct. 27 in the Jour A studyby investigators attheSchoolofMedicine The jury’s stillout onrock ’n’ roll. But thelinkbe- a particularly valua particularly - alike. searchers and participants — hascaptured theimaginationofre- — aconceptknown asprecision health Purchase, a resident of Mill Valley, is See MITCH M/SHUTTERSTOCK.COM MITCH See MARIJUANA, page6 BASELINE, page7 Page 4 improvement. evidence of showed some young donors plasma from received blood disease who with Alzheimer’s participants Clinical trial STEVE FISCH - Ann Arvin, dean of research, to step down after 12 years

By Lisa Lapin Stanford. It is a demanding job and we are all in her expand their innovative programs. debt.” These successes are owed to dynamic faculty direc- Ann Arvin, MD, has announced that she will step The core mission of the research office is to facilitate tors and the commitment of the president, provost, and down as the vice provost and dean of research at Stan- the many diverse faculty-led research programs, which school deans and associate deans for research, as well ford in the fall of 2018. She will have served for 12 years led to more than $1.2 billion in extramural support at as the development team created to support the inter- in the role. Stanford and SLAC National Accelerator Laboratory disciplinary centers and institutes and their dedicated A professor of microbiology and immunology, Arvin in 2016, through the work of seven administrative of- volunteer advisory councils, Arvin said. will return to research and teach- L.A. CICERO / STANFORD NEWS SERVICE fices, together with the Office of ‘A visionary leader’ ing. Provost Persis Drell, PhD, Research Administration. Major will appoint a search committee objectives have been helping to “Ann has been a visionary leader of interdisciplin- in the coming weeks and begin provide state-of-the-art shared ary themes at Stanford,” said Carla Shatz, PhD, direc- the process of finding a successor. facilities that are essential for tor of Stanford Bio-X and professor of biology and of “It has been my great privi- contemporary research — from neurobiology. “She recognized the power and benefit of lege to work with our faculty research computing and nanosci- creating opportunities for research and training across and their students as they pur- ences to digital humanities and the university long before many of our peer institutions, sue Stanford’s long and valued the Stanford Center at Peking and she helped transform the way scientific research is tradition of research and schol- University, and most recently the being done.” arship in the disciplines while Stanford-SLAC cryo-electron mi- Arvin has also guided key research support enter- also addressing major societal croscopy facility — and support- prises, including the Office of Environmental Health challenges,” said Arvin, who ing the faculty and research staff and Safety; the Export Control Office; the Office of Sci- holds the Lucile Salter Packard who ensure the excellence of these ence Outreach; the Research Compliance Office, which Professorship in Pediatrics. “My important facilities. oversees research involving human subjects and animals; primary objective has been to Arvin’s work to help forge and the Office of Technology Licensing. The Office of support the remarkably collabor- connections between researchers International Affairs was created under her purview. ative spirit that enables Stanford throughout the university is exem- During Arvin’s tenure, new web-based tools have researchers to cross the tradi- plified by the growth of Stanford’s also been developed to aid research, including an online tional disciplinary boundaries in Ann Arvin will return to research and teaching after interdisciplinary institutes. Her system for financial interest disclosures; the DoResearch their search for solutions to the stepping down as the dean of research next fall. goal has been to support the dedi- site, which gives user-friendly access to policies and pro- most fundamental research ques- cated efforts of the faculty direc- cedures; and the expansion of Stanford Profiles to share tions, and to the most pressing tors aiming to create intellectual the research and scholarly interests and publications of problems of the global community. I am very grateful and physical environments that inspire dialogue across faculty and trainees within and beyond the university. to Stanford’s many knowledgeable, talented administra- disciplines, enhance innovation and engage faculty and Prior to assuming her role as vice provost and dean tors, and especially our VP DoR team, who were indis- trainees from all seven schools. of research, Arvin served as associate dean of research pensable to this effort. Having a chance to help create “Ann has viewed her role as that of a supporter to from 2001 to 2006, and was chief of the infectious dis- opportunities for faculty and students to explore their all of Stanford’s research enterprise, and as an advocate ease division of the Department of Pediatrics and Lucile most promising ideas in an environment that facilitates to assure our researchers thrive and can easily collabo- Packard Children’s Hospital from 1984 to 2006. their success has been a deeply rewarding experience.” rate,” said Stanford President Marc Tessier-Lavigne, Arvin received her bachelor’s degree in philosophy Arvin has made it her chief priority to engage with PhD. “She understands that Stanford’s remarkable suc- from Brown University, her master’s degree in phi- faculty directors to optimize the contributions of Stan- cess in research lies with our innovative, creative faculty, losophy from Brandeis University and her medical de- ford’s 18 universitywide interdisciplinary laboratories, and she has done remarkable work in enabling them gree from the University of Pennsylvania in 1972. She centers and institutes, encompassing the life and physi- to work together, across disciplines, and to be success- completed her pediatrics residency at the University of cal sciences, humanities and social sciences. She placed ful even within a challenging environment for research California-San Francisco, and subspecialty training in an equal focus on the day-to-day implementation of funding.” infectious diseases at UCSF and Stanford. Faculty Senate policies that embody core principles and During her tenure, five interdisciplinary institutes Her principal research interests are human herpes vi- shared values, including openness in research, academic were launched or became established programs, in- ruses and childhood viral diseases and vaccines. She is a freedom and the responsible conduct of research. cluding the Woods Institute for the Environment, fellow of the American Academy of Arts and Sciences, Advocate for sound federal research policies the Precourt Institute for Energy, the Stanford Center the National Academy of Medicine, the American Asso- for Longevity, the Stanford Neurosciences Institute, ciation for the Advancement of Science, the Infectious Throughout her service, Arvin has also represented and Chemistry, Engineering & Medicine for Human Disease Society of America and the American Pediatric the university nationally to advocate for sound federal Health (ChEM-H); Spectrum, the Stanford Center Society. She is the recipient of an NIH MERIT award, research policies, serving most recently on two National for Clinical and Translational Research and Education, and has been given honors for basic and translational re- Academy committees to reduce the burden of research was established with the School of Medicine; and the search, including the University of Pennsylvania School regulations and foster research integrity at universities. Center for Advanced Study in the Behavioral Sciences of Medicine Distinguished Graduate Award, the Stan- “Stanford has been extremely fortunate to benefit joined Stanford. During this time, Bio-X, the Freeman ford University School of Medicine Dean’s Medal and from Ann’s deep understanding of the issues facing re- Spogli Institute for International Studies, the Stanford Albion Walter Hewlett Award, the E. Mead Johnson searchers, her strategic vision for new research avenues, Institute for Economic Policy Research, the Stanford Award for Research in Pediatrics and the John Enders and her dedicated and extensive national service in Humanities Center, the Geballe and Ginzton laborato- Award in Virology. helping key federal agencies develop regulations and ries, and the joint SLAC-Stanford Institute for Materi- Arvin said she looks forward to having more time for policies,” Drell said. “Ann is one of the most respected als & Energy Sciences, Photon Ultrafast Laser Science her laboratory research in virology and to ensuring that research administrators in the country, and she has been and Engineering Institute, and Kavli Institute for Par- her successor as vice provost and dean of research has a a tremendous advocate for enabling research here at ticle Astrophysics and Cosmology have continued to smooth transition. ISM

Initiative aims to help develop innovative companies for brain health By Tracie White Tank-style competition between virtual treat diseases like PTSD, autism, anxiety research team from Simon Fraser Uni- Brainstorm, an initiative that aims to reality researchers. and opioid use,” said Nina Vasan, MD, versity in Canada that is investigating foster creative and entrepreneurial com- “Virtual reality and augmented reality a psychiatry resident and MBA student the use of neurosensors connected to a panies to improve brain health, launched offer exciting potential to transform the at Stanford, and founder and director of virtual reality system designed to help recently with an event featuring a Shark way that we as physicians diagnose and Brainstorm. “Brainstorm wanted to cap- determine what can trigger a relapse in a ture this potential by identifying prom- recovering addict. Inside Stanford Medicine is ising VR/AR applications and working Brainstorm, whose interdisciplinary published monthly in July and with entrepreneurs to develop their ideas team members hail from across Stanford STANFORD December and semi-monthly into successful ventures.” and the nation, is a special initiative of

INSIDE the rest of the year. Six teams made the finals in October. Laura Roberts, MD, professor and chair MEDICINE They included a high school team that of psychiatry and behavioral sciences at is produced by Paul Costello presented a virtual reality game which Stanford. Office of Communication & Public Affairs Chief communications officer simulates what it’s like to have schizo- The initiative provides courses and Stanford University Susan Ipaktchian phrenia, and a team of researchers from educational materials and hosts regu- School of Medicine Director of print & 3172 Porter Drive Web communications the Medical College of Wisconsin that lar events supporting the growth of en- Palo Alto, CA 94304 John Sanford designed a video game for promoting trepreneurial ideas in the field of brain Mail code 5471 Editor real-time tools for overcoming anxiety. health, Vasan said. (650) 723-6911 Robin Weiss The teams came from across the coun- “We wanted to bring the Silicon Val- http://med.stanford.edu/news/ Graphic designer try to appear before a panel of judges at ley-style of problem-solving to psychia- the Li Ka Shing Center for Learning and try,” Vasan said. “Our goal is to bring Send letters, comments and story ideas to John Knowledge. The event was part of Stan- together pioneering people and create in- Sanford at 723-8309 or at [email protected]. ford’s annual Innovations in Psychiatry novative technology and companies that Please also contact him to receive an e-mail version of Inside Stanford Medicine. and Behavioral Health conference. will transform the way brain and behav- The winner of the competition was a ioral health is addressed.” ISM 2 NOVEMBER 6, 2017 INSIDE STANFORD MEDICINE Stanford Medicine Advisory Council charter is revised and formalized Livingston appointed university initially established by President John include the dean and three department and Stanford Medicine. liaison for Stanford Medicine Hennessy,” Byerwalter said. “President chairs from the School of Medicine; the “I look forward to working with Lloyd Tessier-Lavigne has enhanced the coun- CEOs, board chairs and members of the Minor, David Entwistle and Christopher By Kathleen Sullivan cil’s charge, formalized its role, and we board of directors of Stanford Health Dawes to enhance the day-to-day work- have worked together to ensure that Care and Lucile Packard Children’s Hos- ing relationship between Stanford Medi- Stanford President Marc Tessier-Lavi- Stanford Medicine and the university pital Stanford; current and former mem- cine and the university,” Livingston said. gne, PhD, has worked with Stanford’s collaborate and execute with greater inte- bers of the Stanford University Board of “Stanford Medicine is an invaluable biomedical leaders to formalize an ad- gration. We look forward to a productive Trustees; the university liaison for Stan- university asset, and this new structure visory council to consult and work with year as we meet challenges and identify ford Medicine; and Stanford’s general will allow us to further inform and ed- the university and Stanford Medicine on opportunities where Stanford is uniquely counsel. ucate the entire Stanford community matters of strategic and operational im- positioned to lead.” The advisory council will: about the incredible biomedical initia- portance affecting the School of Medi- An ‘invaluable role’ • Review and advise on the compre- tives underway across our campus — cine, Stanford Health Care and Lucile hensive strategic plan for Stanford Med- many of which involve members of our Packard Children’s Hospital Stanford. Lloyd Minor, MD, dean of the School icine that is being developed and con- six other schools beyond medicine.” In addition, a new role of university of Medicine, said he was “extraordinarily duct periodic reviews of progress relative Livingston has many responsibilities liaison for Stanford Medicine will be pleased” by the evolution of the Stanford to the plan. as university liaison, including keeping filled by Randy Livingston, MBA, vice Medicine Advisory Council. • Serve as a sounding board to Stan- university leadership informed about president of business affairs and chief fi- “Since its inception, the council has ford Medicine leadership and gover- the performance, operations, strategy nancial officer at Stanford. worked tirelessly to support and promote nance on strategic and ma- L.A. CICERO / STANFORD NEWS SERVICE “Although the advisory council has the Principles of Stanford Medicine, jor operational issues, such been in existence for a few years, the de- which articulate the critical importance as land use, financial plan- cision to revise and formalize its charter of all three aspects of the Stanford Medi- ning assumptions and other emerged from conversations with many cine mission: research, teaching and pa- issues of common interest to people, including our clinical faculty tient care,” Minor said. “By formalizing Stanford Medicine and Stan- chairs and biomedical leaders, about how the council and appointing a university ford University. we could all better engage and more ef- liaison, we are shining an even brighter • Coordinate develop- fectively collaborate,” Tessier-Lavigne light on our indispensable connection to ment of, and periodically re- said. “It was also clear that we needed a the whole campus community.” view and comment on, Stan- designated person from the university to Both hospital leaders concurred that ford Medicine’s consolidated be a liaison, to bring new ideas and initia- the formalized council will help the med- capital plan, financial pro- tives to our attention. I’m pleased Randy ical entities advance and plan together. jections and financial per- has agreed to serve in that key role.” “The advisory council will play an formance, including interim The chair of the advisory council is invaluable role as we pursue new oppor- integrated review of financial Mariann Byerwalter, MBA, who has a tunities to strengthen and integrate each performance on a quarterly long history of service and commitment facet of the Stanford Medicine tripartite basis. to the Stanford community. She has mission,” said David Entwistle, president • Conduct ad hoc reviews served three terms on the Stanford Uni- and CEO of Stanford Health Care. “It of specific issues and excep- versity Board of Trustees and has served will also help enable us to respond effec- tional matters, such as the more than two decades on the boards of tively to ongoing changes in the health status and costs of opening Randy Livingston will be responsible for extending collaboration and ensuring coordination on nonacademic matters between the directors of both hospitals. She chaired care landscape.” and/or transitioning to the university and Stanford Medicine. the board of directors of Stanford Health “The revisions to the charter and the new hospitals. Care from 2006 to 2013 and was in- appointment of Randy Livingston as li- Livingston will retain his terim president and CEO of Stanford aison will greatly enhance communica- existing roles as vice president of busi- and capital plans for each entity of Health Care in 2016. At the university, tion and alignment,” said Christopher ness affairs and chief financial officer Stanford Medicine, bringing university she was vice president for business affairs Dawes, president and CEO of Stanford while assuming his new role as university concerns to the attention of Stan- and chief financial officer from 1996 to Children’s Health. liaison for Stanford Medicine. ford Medicine leadership, and serving 2000. Currently, she chairs the board of In September, the 20-member advi- As university liaison, Livingston is on the Stanford Medicine Advisory directors of SRI International. sory council held its first meeting of the responsible for extending collaboration Council and the boards of Stanford “I am honored to chair the Stanford 2017-18 academic year. and ensuring coordination on nonaca- Health Care and Lucile Packard Chil- Medicine Advisory Council, which was The members of the advisory council demic matters between the university dren’s Hospital Stanford. ISM

Multidisciplinary care team prevails against heart defect in newborn

By Erin Digitale Physicians in the hospital’s Fetal and Pregnancy heart defects. “Whether a baby is in the NICU or the Health Program assessed Kennedy’s heart with a de- CVICU, they’re going to see both a neonatologist and Marlo Greenfield was halfway through her preg- tailed fetal echocardiogram. They recommended that a cardiac intensivist every day,” Rhine said, referring nancy when she and her husband, David, received bad the family move to Palo Alto from their home in Oak- to the neonatal ICU and the cardiovascular ICU. “We news: Their eagerly awaited COURTESY OF THE GREENFIELD FAMILY ley, California, a few weeks before think it represents the highest standard of care.” daughter had a congenital heart Marlo’s due date so that Ken- Ready for surgery defect. nedy could be born at Packard The fetal aorta and left side Children’s. On July 31, at 7 days old, Kennedy was ready for of the heart were smaller than On July 24, soon after the surgery. In a five-hour procedure, Katsuhide Maeda, normal, ultrasound scans indi- move, Marlo’s water broke. Ken- MD, clinical associate professor of cardiothoracic sur- cated. At first, the couple was nedy arrived a few hours later, and gery, and his team put Kennedy on a heart-lung bypass told the problem might resolve several Packard Children’s neona- machine and carefully removed the too-small portion on its own, but over the next tologists and cardiologists imme- of her aortic arch. Once the abnormally narrow region several weeks of Marlo’s preg- diately began working to stabilize of blood vessel was gone, Maeda reconstructed an aor- nancy, follow-up scans did not her. tic arch from the infant’s own blood vessel tissue. “This show enough catch-up growth. Kennedy was started on medi- is a relatively straightforward procedure for our team,” The baby, whose parents cation that would help maintain Maeda said. planned to name her Kennedy, her circulation until surgery. Her Kennedy did well, staying for four days in the would need heart surgery in her caregivers in the neonatal inten- CVICU and then transferring back to the NICU. Her first few days of life to ensure sive care unit, led by neonatologist multidisciplinary care team followed her the whole she could get enough oxygen. William Rhine, MD, professor of time. “It was very scary informa- pediatrics at the School of Medi- “Every time we spoke to someone, they knew exactly tion to hear when we were hop- cine, watched her closely. what was going on with Kennedy,” Marlo said. “Every ing for a healthy baby,” David “There’s a certain amount of single person was on the same page. They really knew said. When Marlo was 32 weeks stabilization that occurs in the what they were doing and had it under control.” pregnant, she was referred to Kennedy Greenfield was treated for a heart defect at first few days of life,” Rhine said. The coordination will continue after the cardio- the Johnson Center for Preg- Lucile Packard Children’s Hospital Stanford. “The blood pressure in the baby’s vascular intensive care unit relocates to the new main nancy and Newborn Services lungs drops; you want that to building of Packard Children’s when it opens in Decem- at Lucile Packard Children’s Hospital Stanford, which occur before you do cardiac surgery. We also evaluate ber. The NICU will stay in the hospital’s west building, helped the couple feel more confident about what was other organ systems, such as the brain and kidneys, to and will eventually expand as existing hospital spaces coming. make sure they are ready for surgery.” are renovated and repurposed into a world-class mother Assessing heart with echocardiogram From the start, Kennedy was also being monitored and baby center over the next few years. by a cardiac intensivist, a pediatric cardiologist who In the meantime, Kennedy has been home with her “Knowing we would be at one of the best hospitals specializes in cardiac care in the intensive care unit. family in Oakley since August. in the nation, with doctors and nurses that strictly deal The close collaboration between doctors from differ- “She’s absolutely beautiful, very content and happy,” with children and pregnant women, was reassuring,” ent specialties is a hallmark of the top-notch care Pack- David said. “Of course, I’m a little biased, but I think David said. ard Children’s offers to children born with congenital she’s perfect in every way.” ISM INSIDE STANFORD MEDICINE NOVEMBER 6, 2017 3 Clinical trial finds blood-plasma infusions for Alzheimer’s safe, promising

By Bruce Goldman a senior research career scientist at the tion). Neither the participants nor those ascertain mood, cognition and func- Veterans Affairs Palo Alto Health Care administering the infusions knew which tional ability of the participants were ad- School of Medicine investigators have System, whose research has shown that of the two infusions any given partici- ministered to either participants or their reported success in an early-phase clini- factors in the blood of young mice can pant was getting. Then, after a six-week caregivers before and after the first four- cal trial examining the safety, tolerability rejuvenate the brain tissue and improve “washout” period, the regimens were re- week infusion period, and again before and feasibility of administering infusions cognitive performance in old mice. versed: Those initially receiving plasma and after the second four-week infusion of blood plasma from young donors to Larger studies needed got four weekly infusions of placebo, and period. participants with mild to moderate Al- vice versa. The total time elapsing between a par- zheimer’s disease. There were also some Sha, the clinical core co-leader of the “Those participants served as their ticipant’s first and final visits, including signs suggesting improvements in par- Stanford Alzheimer’s Disease Research own controls,” said Sha. a preliminary screening and a final visit, ticipants’ conditions. Center and the medical director of the Multiple tests and questionnaires to approached six months. The participants Results from the PLASMA trial, short Stanford Neuroscience Clinical Trials needed to make nearly a dozen round for Plasma for Alzheimer’s Symptom Group, cautioned that these assessments PAUL SAKUMA trips to Stanford, accompanied by theier Amelioration, were presented Nov. 4 were based on caregiver reports and that caregivers. So, to reduce the travel bur- at the 10th annual Clinical Trial on Al- the number of participants in the study den, the investigators decided to modify zheimer’s Disease conference in Boston — 18 — was small. Further studies on the design for their next group of nine by Sharon Sha, MD, a clinical associate larger numbers of participants will be participants. These newcomers all re- professor of neurology and neurological necessary before conclusions about effi- ceived young-donor plasma infusions, sciences at Stanford and the trial’s princi- cacy can be reached, Sha said. and they and their caregivers, as well pal investigator. The trial took place at Stanford Hos- as the administrators, all knew it. This Sha noted that the finding of safety pital and was sponsored by Alkahest, a change cut the time between the first and wasn’t surprising, given that blood- privately held biotechnology company final visits to 10-12 weeks for the sec- plasma infusions have long been in wide- headquartered in San Carlos, California. ond group of participants, and required spread use for other indications and are Alkahest holds intellectual property asso- commensurately fewer trips. These par- considered extremely safe. More surpris- ciated with the treatment regimen. Wyss- ticipants, like the first group, received ing, she said, were hints of recipients’ Coray, a co-founder of the company and the full battery of mood, cognition and improvement on tests of functional abil- chair of its scientific advisory board, con- functional-ability assessments. ity: the capacity to perform basic tasks tinues to work full-time at Stanford. He Only a single instance of a trial-re- essential to independent daily life, such was not involved in the clinical study. lated adverse event — excessive itching as remembering to take medications and The trial proceeded in two stages. In — occurred. Sha said this wasn’t entirely being able to pay bills and prepare one’s the first stage, nine participants with unanticipated, as it can arise as a side ef- own meals. mild to moderate Alzheimer’s disease fect of the infusion of any blood prod- The PLASMA trial was designed were given four weekly infusions either uct. Another participant had a stroke, to test a hypothesis advanced by Tony of plasma — the liquid, cell-free part of Sharon Sha led a safety trial in which participants but this was considered unrelated to the Wyss-Coray, PhD, Stanford professor of blood — obtained from donors 18-30 with Alzheimer’s receiving blood plasma from young treatment; the participant had received neurology and neurological sciences and years old, or of placebo (a saline solu- donors showed some evidence of improvement. only four infu- See PLASMA, page 5

New study finds drawbacks to robot-assisted kidney removal

By Krista Conger in a subsequent increase in operating room and instru- patients whose surgeon used mentation costs, the researchers speculated. the robot had a total procedure Robot-assisted laparoscopic surgery to remove a pa- Chung is the senior author of the study, which was time of more than four hours. tient’s entire kidney requires slightly longer operating published Oct. 24 in JAMA. The lead author is former In contrast, about 28.5 percent times and results in increased costs compared with the Stanford visiting scholar In Gab Jeong, MD, PhD. of the patients whose surgeon use of traditional laparoscopic surgery, according to a The dexterity of robots used the conventional laparo- large, multiyear analysis conducted by researchers at the scopic procedure were in the School of Medicine. Surgical robots are helpful because they offer more operating room for more than However, the two approaches have comparable pa- dexterity than traditional laparoscopic instrumentation four hours. tient outcomes and lengths of hospital stay, the study and use a three-dimensional, high-resolution camera to On average, the total hos- Benjamin Chung showed. Laparoscopic surgery is a minimally inva- visualize and magnify the operating field. Some proce- pital cost (including the cost sive procedure in which surgical operations are done dures, such as the removal of the prostate or the removal of supplies, room and board, through small incisions. The removal of the entire kid- of just a portion of the kidney, require a high degree pharmaceuticals and operating room time) for the ro- ney is called a radical nephrectomy. of delicate maneuvering and extensive internal suturing bot-assisted procedure exceeded that of the traditional “Although the laparoscopic procedure has been stan- that render the robot’s assistance invaluable. But Chung laparoscopic procedures by about $2,700 per patient. dard of care for a radical nephrectomy for many years, and his colleagues wondered whether less technically The researchers speculated that the increased cost may we saw an increase in the use of robotic-assisted ap- challenging surgeries, such as the removal of a whole be due to longer times spent in the operating room and proaches, and by 2015 these had surpassed the number kidney, may not benefit as significantly from a robot’s the disposable instruments upon which surgical robots of conventional laparoscopic procedures,” said Benja- help. rely. min Chung, MD, associate professor of urology. “We The researchers analyzed data from 416 hospitals Why use robotic assistance? found that, although there was no statistical difference across the country from 2003 to 2015. They found in outcome or length of hospital stay, the robotic-as- that in 2003 about 65 percent of patients with kidney The increase in robot-assisted surgery for many pro- sisted surgeries cost more and had a higher probability tumors that necessitated the removal of the entire or- cedures may be due to a variety of factors, the research- of prolonged operative time.” gan underwent an open surgical procedure. About 34 ers said. The technology clearly benefits patients for The discrepancy may be due to the time needed for percent had their kidney removed using a laparoscopic certain types of surgeries. In other situations, there may robotic operating room setup or due to a surgeon being procedure, and only the remaining 1.5 percent of cases be an expectation on the part of the hospital or the sur- in the earlier part of his or her learning curve, resulting were conducted with robot-assisted surgery. By 2015, geons themselves to justify the large initial investment

MASTER VIDEO / SHUTTERSTOCK.COM the proportion of pa- in purchasing the robot by using it for many types of tients who underwent procedures. And, regardless of the procedure, use of the the open procedure robotic platform can assist the surgeon in many ways to had decreased to about make the operation more comfortable for the surgeon. 50 percent, but the use Finally, patients themselves may view robot-assisted sur- of robot-assisted lapa- gery as more technologically advanced. roscopic surgery for Chung noted that the study covers a time period the remaining cases when many physicians were just learning to use the ro- had surpassed that bots for this type of procedure; as time passes, it’s pos- of traditional laparo- sible the operating time will decrease and that the cost scopic surgery, 27 per- differences between the two procedures will narrow. But cent to 23 percent. for now, the study suggests that robot-assisted surgery When they pooled isn’t always the right choice. the data across the “There is a certain incentive to use very expensive years, the research- equipment,” said Chung. “But it is also important to ers found that among be cognizant as to how our health care dollars are being nearly 24,000 pa- spent. Although robotic surgery has some advantages, tients, almost 19,000 are those advantages relevant enough in this type of case underwent a tradi- to justify an increase in cost?” tional laparoscopic Other Stanford authors of the study are former re- procedure and about search scholar Yash Khandwala; and former visiting 5,000 underwent a scholars Jae Heon Kim, MD, PhD, and Deok Hyun robotic-assisted proce- Han, MD, PhD. Robot-assisted surgeries for kidney removal have been on average less cost-effective and more lengthy than dure. They found that Stanford’s Department of Medicine supported the traditional laparascopic nephrectomies, according to a new study. 46.3 percent of those work. ISM 4 NOVEMBER 6, 2017 INSIDE STANFORD MEDICINE Technology invented by researchers ties brain circuits to alertness

STEVE FISCH By Bruce Goldman and radiating to regions throughout the brain. Stanford investigators have for the Importantly, the researchers extended first time tied several brain circuits to their findings to mice, confirming that alertness. the same circuits tied to alertness in ze- The findings enhance scientists’ un- brafish are acting similarly in mammals, derstanding of the forces driving alert- whose ancestors split from those of ze- ness, a brain state that’s essential to brafish hundreds of millions of years ago. survival, by showing that diverse cell “This tight conservation of alertness-pro- types throughout the brain together pro- moting circuits over such long epochs of duce this state. evolutionary time — longer than human Problems tied to alertness deficits and mouse lineages have been separated range from sleep deprivation to depres- — strongly implies relevance to humans sion to brain-trauma-induced somno- as well,” said Deisseroth, who holds the lence, while conditions such as anxiety, D.H. Chen Professorship. mania and post-traumatic stress disor- The Stanford scientists call the new der are often characterized by excessive method they developed MultiMAP, alertness. which is short for Multiplexed-alignment The researchers employed a cutting- of Molecular and Activity Phenotypes. It Karl Deisseroth and his colleagues were able to simultaneously monitor activity in every nerve cell of a edge technology that allowed them to let them track the activity of nearly every zebrafish’s brain and determine which types of neurons were tied to alertness. monitor vast numbers of nerve cells’ ac- neuron in the zebrafish brain and then tivity in the brain simultaneously and, identify the cell type of every neuron of afterward, to characterize the cells of interest — the crucial step in determin- appear in or on one but not another neu- Guided by their findings in zebrafish, interest in molecular detail. This new ing which neuronal circuits are partici- romodulatory cell type. the researchers then targeted the equiva- method lets scientists record the activ- pating in the induction of a brain state The zebrafish Deisseroth’s group lent neuronal populations in the much ity of any cell type, without needing to such as alertness. looked at were only 7-10 days old — a more complex brains of mice. To test produce special, genetically modified “We looked at every neuron in the time when their bodies are only a few mice’s reaction times, they trained the animals for each new experiment. fish’s brain during life, when those cells millimeters in length and still relatively mice to lick in response to a particular In a study published online Nov. were actively firing, and learned which transparent, yet are able to execute com- tonal cue; when the mice did so, they were 2 in Cell, Karl Deisseroth, a Howard cells were most active at moments when plex behavior. This feature, along with a rewarded with a drop of drinking water. Hughes Medical Institute Investiga- we knew that the fish was most alert,” few tricks the scientists cooked up, per- Deisseroth’s team observed almost tor and professor of bioengineering and said Deisseroth. “Then, after the fish’s mitted direct brain-wide optical inspec- precisely the same activity patterns in of psychiatry and behavioral sciences brain tissue was preserved with a fixative tion of neural activity. these equivalent circuits in mice that they at Stanford, and his colleagues describe without altering relative positions of cells Bioengineered fish had seen in those of the fish. how they managed to observe activity in within the fish’s head, we could target The scientists went one step further nearly every nerve cell, or neuron, in the those neurons with molecular probes and The fish had been bioengineered so in the mice: They used optogenetics — brains of larval zebrafish while tracking determine their cell types.” that calcium flux within a neuron — an a technology, developed in Deisseroth’s the creatures’ reaction times in response In particular, the investigators wanted excellent proxy for impulse conduction lab, that allows neurons to be excited or to a stimulus. (Studies in humans and to explore the activity of the brain’s neu- within that cell — triggered a fluores- inhibited by a pulse of light at the flick other animals have shown that reaction romodulatory circuitry. Distinct from cent signal that could be picked up and of a switch — to prove, by variously ac- times are faster when the subject is more their more binary cousins — some 98 recorded via high-powered microscopy. tivating or inhibiting neurons in one or alert). The activity of each neuron was percent of neurons in the brain act by The researchers constrained the fish’s another population, that only a subset of then linked to that neuron’s particular either exciting or inhibiting downstream heads by embedding each tiny animal in the circuits in question were individually cell type. With this brainwide dragnet, nerve cells — clusters of neuromodula- an agarose gel. They carved the gel away capable of increasing alertness. One was Deisseroth and his associates were able tory neurons send out projections that from the fish’s tail, whose movements the set of neurons coming from the locus to determine the identities of several branch throughout the brain and act less would be key to their experiments. coeruleus; this set operates by secreting distinct neuronal circuits not previously like on/off switches than like colors on an To test alertness, the investigators the substance norepinephrine. Another suspected to be associated with alertness. artist’s palette. Rather than excite or in- presented the fish with a visual stimulus was an understudied group of so-called The study’s lead author is postdoctoral hibit, they instead add nuance by secret- suggestive of an approaching predator. CART neurons, previously known to be scholar Matthew Lovett-Barron, PhD. ing substances that render excitatory and This evokes an instinctive tail-swishing responsive to cocaine and amphetamines, Extending findings to mice inhibitory neurons more or less likely to response, as the fish attempts to veer in a brain region called the Edinger- fire under various circumstances. away from impending danger. Each of Westphal nucleus; and the third was a It turns out that alertness involves Different types of neuromodulatory 34 separate larval zebrafish was subjected group of acetylcholine-secreting neurons more than a single on/off switch. Prior neurons can be distinguished not only to repeated exposures to the looming- in a deep-brain structure called the lateral to the new study, alertness in vertebrates by the different kinds of substances they predator stimulus. The time elapsed be- dorsal tegmentum. Other cell types cor- was thought to be primarily controlled secrete, such as dopamine, acetylcho- tween each exposure and the consequent related with alertness did not directly in- by a set of neurons emanating from a line and serotonin, but also by various swishing of the fish’s tail — the animal’s fluence the behavior; Deisseroth said he brain structure called the locus coeruleus biological markers, such as proteins that reaction time — was measured. In each thinks these neuromodulatory circuits, instance, fluorescence representing activ- rather than directly triggering alertness, ity within tens of thousands of nerve cells report on its status to other brain circuits. just prior to the stimulus was captured The new findings open the door to and recorded. a whole new route of further explora- Plasma the investigators themselves knew they After humane euthanasia and preserv- tion, Deisseroth said. “The more we un- continued from page 4 were getting plasma; this could perhaps ing the fish tissue in fixative, the team derstand the landscape of neurons that predispose caregivers to optimistic re- directed fluorescence-labeled molecular underlie a brain state like alertness, the sions of saline and, furthermore, had suf- porting. But examination of the data in- probes at the animals’ neurons and im- more we understand the brain state con- fered the stroke at the end of the ensuing dicated that, to the contrary, it was the aged the results. Using algorithms, they cept itself — and we may even be able to washout period, during which no infu- first group of participants — who had no were able to align the neural-activity data help design brain-state targeted clinical sions of any kind were administered. idea whether they were getting plasma from their experiments on live zebrafish interventions.” Improvements in functional ability or placebo — who showed the most im- with cell-identity data extracted after- Other Stanford co-authors are basic provement in functional ability after re- ward from those same fish. life research scientist Aaron Andalman, An analysis of assessments once all ceiving plasma infusions. Deisseroth and his colleagues identi- PhD; graduate students William Al- participants had been treated showed no “Our enthusiasm concerning these fied multiple anatomically and biochem- len, Sam Vesuna and Isaac Kauvar; and significant changes in participants’ mood findings needs to be tempered by the fact ically distinct populations of neurons former graduate student Vanessa Burns, or their performance on tests of cogni- that this was a small trial,” Sha said. “But that were most active just before the PhD. tion involving tasks such as memorizing these results certainly warrant further fishes’ fastest responses to the looming- The study was funded by the Helen lists or recalling recent events, Sha said. study.” predator stimulus. One of these was Hay Whitney Foundation, the Brain These kinds of changes are typically ob- Alkahest has stated in a news release the norepinephrine-secreting popula- and Behavior Research Foundation, the served only in clinical trials whose dura- that based on the safety profile and sig- tion originating in the locus coeruleus, National Institute of Mental Health, tions exceed one year, she added, so the nals of efficacy seen in the PLASMA already well-known to be involved in the National Institute on Drug Abuse, absence of an effect here wasn’t particu- trial, it is planning to advance the clinical alertness. This was reassuring, Deisseroth the Defense Advanced Research Proj- larly unanticipated. development of a next-generation, pro- said, because it indicated that the ap- ects Agency NeuroFAST program, the But on two of three different assess- prietary plasma-derived product for the proach was valid. Howard Hughes Medical Institute, the ments of functional ability, participants treatment of mild to moderate Alzheim- But the dragnet snagged several other NOMIS Foundation, the Else Kroner showed statistically significant improve- er’s disease. neuromodulatory populations of neu- Fresenius Foundation, the Wiegers Fam- ment — this, despite the trial’s small size. “I’m excited to see that giving re- rons as well, including cells that release ily Fund, the James Grosfeld Founda- “That was surprising, to me,” said peated infusions of plasma to elderly acetylcholine, serotonin, dopamine and tion, the HL Snyder Foundation and the Sha. “The trial wasn’t powered to show people with Alzheimer’s disease is safe the peptides CART, somatostatin and National Science Foundation. efficacy.” and that we can move forward to larger neuropeptide-Y. While all these popu- Stanford’s departments of Bioengi- At first, the investigators suspected studies,” Wyss-Coray said. “But I’m also lations’ activity levels correlated with neering and of Psychiatry and Behavioral that the report of improvements in func- realistic enough to know that it is very alertness, they didn’t correlate in perfect Sciences also supported the work. The tional ability might have been driven easy to cure diseases in small animals lockstep with one another, suggesting Department of Bioengineering is jointly by the second group of participants, and a million times more difficult in hu- that each population has its own slightly operated by the School of Medicine and who along with their caregivers and mans.” ISM different job to do. the School of Engineering. ISM INSIDE STANFORD MEDICINE NOVEMBER 6, 2017 5 STEVE FISCH Marijuana who smoke it; on the other hand, experi- continued from page 1 ments conducted in animal models and “Frequent marijuana use doesn’t seem humans indicate that marijuana stimu- to impair sexual motivation or perfor- lates activity in brain regions involved in mance. If anything, it’s associated with sexual arousal and activity. increased coital frequency,” said the Looking at survey responses study’s senior author, Michael Eisenberg, MD, assistant professor of urology. The To arrive at an accurate determina- lead author is Andrew Sun, MD, a resi- tion of marijuana’s effect on intercourse dent in urology. frequency, Eisenberg and Sun turned to Hint of a causal connection the National Survey of Family Growth, sponsored by the federal Centers for Dis- The study does not establish a causal ease Control and Prevention. The survey, connection between marijuana use and which provides data pertaining to fam- sexual activity, Eisenberg noted. But the ily structures, sexual practices and child- results hint at it, he added. “The overall bearing, reflects the overall demographic trend we saw applied to people of both features of the U.S. population. Origi- Michael Eisenberg is the senior author of a study that is the first to examine the relationship between sexes and all races, ages, education lev- nally conducted at regular intervals, the marijuana use and frequency of sexual intercourse at the population level in the United States. els, income groups and religions, every survey is now carried out on an annual health status, whether they were married basis. It explicitly queries respondents on weeks. demographic, health, marital or parental or single and whether or not they had how many times they’ve had intercourse Some 24.5 percent of men and 14.5 status. kids.” with a member of the opposite sex in percent of women in the analysis re- In addition, the trend remained even The study is the first to examine the the past four weeks, and how frequently ported having used marijuana, and there after accounting for subjects’ use of other relationship between marijuana use and they’ve smoked marijuana over the past was a positive association between the drugs, such as cocaine or alcohol. This, frequency of sexual intercourse at the 12 months. frequency of marijuana use and the fre- Eisenberg said, suggests that marijuana’s population level in the United States. The investigators compiled answers to quency of sexual intercourse. This rela- positive correlation with sexual activity “Marijuana use is very common, but those questions for all years since 2002, tionship applied to both sexes: Women doesn’t merely reflect some general ten- its large-scale use and association with when the survey first began collecting denying marijuana use in the past year, dency of less-inhibited types, who may sexual frequency hasn’t been studied data on men as well as women. They in- for example, had sex on average 6.0 be more inclined to use drugs, to also be much in a scientific way,” Eisenberg said. cluded data from respondents ages 25-45 times during the previous four weeks, more likely to have sex. In addition, co- According to the National Institute and excluded a small percentage (fewer whereas that number was 7.1 for daily ital frequency rose steadily with increas- on Drug Abuse, more than 20 million than 3 percent) of respondents who had pot users. Among men, the correspond- ing marijuana use, a dose-dependent adult Americans are current marijuana failed to answer one or more relevant ing figure was 5.6 for nonusers and 6.9 relationship supporting a possible active users. With the drug’s legalization for questions. for daily users. role for marijuana in fostering sexual medical or recreational use in 29 states, In all, Eisenberg and Sun obtained In other words, pot users are having activity. that number is climbing. But despite data on 28,176 women averaging 29.9 about 20 percent more sex than pot ab- Nevertheless, Eisenberg cautioned, marijuana’s growing status as a recre- years of age and 22,943 men, whose av- stainers, Eisenberg noted. the study shouldn’t be misinterpreted as ational drug, its status as a procreational erage age was 29.5. They assessed these Positive association is universal having proven a causal link. “It doesn’t drug remains ambiguous: On one hand, individuals’ self-reported patterns of say if you smoke more marijuana, you’ll there are reports of erectile dysfunction marijuana use over the previous year and Moreover, Eisenberg said, the posi- have more sex,” he said. in heavy users, and rigorous studies have their self-reported frequency of hetero- tive association between marijuana use Stanford’s Department of Urology found reduced sperm counts in men sexual intercourse over the previous four and coital frequency was independent of supported the work. ISM

Medicine a high level of sustainability, extensive open spaces, a tients and their infants, he said. continued from page 1 sanctuary for spiritual reflection and technologies to David Entwistle, president and CEO of Stanford put children at ease while they undergo challenging Health Care, highlighted Stanford Medicine’s inte- people from underrepresented groups, he said. That procedures, he said. grated strategic plan, in which the two hospitals and compares with 12 percent of PhD students and 14 per- Soft floors, wood paneling in rooms, ubiquitous the medical school are working in concert to determine cent of medical students in 2012. flower boxes, children’s play areas and many other ame- their future direction and how best to get there. “So it’s really wonderful to see the time and effort nities are designed to make the hospital as child- and Planning the future and devotion really coming to benefit in terms of the family-friendly as possible, he said. students we’re attracting,” Minor said. “We’re building “We wanted to create a place that not only would Stanford Medicine has been seeking feedback from an affirming community that is inclusive and represen- cure disease but also a facility that would be nurturing faculty and staff and received 3,700 responses so far. tative of everyone.” and would feel comfortable to young children and their Thirteen working groups have been created to focus

ROD SEARCEY on specific areas, such as digital health, precision health and translational medicine, he said. The collaborative effort is an example of how the three organizations are breaking down barriers and trying to overcome what has been a siloed culture, he said. “Quite frankly, that is what will lead to our suc- cess — that ability to work together and collaborate,” Entwistle said. In response to a question about proposed cuts in health care funding, Entwistle said the hospital has been aggressively fighting back against proposed federal leg- islation that could be “quite frankly catastrophic.” For instance, the recent Graham-Cassidy health bill, which failed to gain sufficient support in the Senate, would have cut $275 billion from Medicaid, including $95 million in California, where the program is known as Medi-Cal, he said. At Packard, the impact of the proposed funding cuts could have been dire, Dawes said. He said 50 percent of children born in California depend on Medi-Cal, and 42 percent of Packard’s patients rely on the feder- ally funded program. A decline in these funds, he said, could have had a “profound” impact on the hospital and the families it serves. “Our first initiative is to try to prevent these changes from happening,” said Dawes. “We need to continue to fighting aggressively any changes to Medicaid and at the same time prepare ourselves to be more cost-efficient.” Given today’s unpredictable political environment, Minor said it’s more important than ever to build a Christopher Dawes discussed some of the features of the expanded Lucile Packard Children’s Hospital Stanford that will open in December. strong community at Stanford Medicine. “In these times of enormous uncertainty in our country, it’s important that we do what we can to build Chris Dawes, president and CEO of Stanford Chil- families,” he said. “We wanted to make sure we had a our community and affirm in our actions the value we dren’s Health, discussed the new children’s hospital, facility that was not ‘institutional.’” have for each other,” he said. “I think that’s really, really which is tentatively scheduled to open Dec. 9. The new The current hospital, which will be called the West important to enable us to be successful internally but facility, driven by the vision of the late Lucile Packard Building, ultimately will be revamped as a mother and also to show the world what a cohesive, highly function- and her daughter, Susan Packard Orr, incorporates baby center, with private rooms serving obstetric pa- ing community can do.” ISM 6 NOVEMBER 6, 2017 INSIDE STANFORD MEDICINE 5 questions Margo Thienemann on guidelines for treating an occasional feature in which an expert answers five questions on a science or policy topic an alarming psychiatric disease in children

For the last five years, a group of clinicians at the Stanford School of Medicine and at lished the first set of peer-reviewed treatment guidelines for PANS and its companion di- Lucile Packard Children’s Hospital Stanford have focused on what happens when the im- agnosis, Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal mune system attacks a child’s brain. Infections, or PANDAS. Margo Thienemann, MD, clinical professor of psychiatry and In Pediatric Acute-Onset Neuropsychiatric Syndrome, which is believed to stem from behavioral sciences at Stanford, is the lead author of the portion of the guidelines that brain inflammation after a triggering infection, children suddenly develop severe obses- address psychiatric and behavioral interventions. Thienemann co-directs Packard Chil- sive-compulsive symptoms and other behavioral problems. They urgently need medical dren’s PANS clinic, the first in the country exclusively devoted to the disease, with Jennifer and psychiatric help. Yet many pediatricians and mental health professionals still lack Frankovich, MD, clinical associate professor of pediatric rheumatology. awareness of how to treat the disorder. Thienemann spoke with Erin Digitale about why the guidelines were needed and To fill the gap, a multidisciplinary team of experts from several universities has pub- what else can be done to raise awareness of the condition.

What do children and families affected by PANS/ we really want them to treat it. out of the hospital or hit someone. Little sounds bother 1PANDAS experience? PANS/PANDAS patients, so the constant beeping of THIENEMANN: Parents often describe children as turning What are some of the most important elements of monitors doesn’t help, and lights bother them, so they into somebody completely different overnight. A child 3 the guidelines? don’t sleep in a hospital setting. It can be very difficult who was functioning just fine might suddenly feel like THIENEMANN: The treatment is at least tri-part. The main on hospital staff. they had been “possessed” by something. They may be thrust of treatment is that if there is a triggering infection, Psychiatric hospitals are also hard for these patients tearful and unable to separate from their parents. They we should treat the infection, and also to tolerate. They have a brain inflam- may suddenly develop vocal or motor tics. The child treat close contacts who may be expos- mation problem, not a behavioral may suddenly, after never having had appreciable ob- ing the child to infection. We also have problem, so typical behavioral interven- sessive-compulsive symptoms, engage in long periods to treat inflammation, which is what we tions aren’t helpful. And in psychiatric of checking behaviors or cleaning behaviors, over and think causes the brain symptoms. settings, parents don’t get to stay with over. It suddenly takes hours to get out of the house or The psychiatric portion of the their children. For many other pediatric get the child to bed. guidelines recognizes that the child psychiatric diagnoses, the parents may In addition to OCD symptoms, the other cardinal and family are really suffering and the be a part of the problem, and some of symptom is food refusal. Kids will suddenly be afraid child needs psychiatric treatment to the process of diagnosis is seeing how to eat for fear they will choke, or fear that the food is help with symptoms. We have to man- the child acts away from parents. But poisoned, contaminated or spoiled. They may say food age the child’s distress so they can get most children with PANS/PANDAS smells awful or express fear of vomiting. Again, this ap- medical treatment, get blood drawn, get have terrible separation anxiety as part pears out of nowhere. MRIs, take medications, so the family of their illness, and it’s very hard on It’s like being hit by a train. Most often, the child can sleep, and the child can sleep. We Margo Thienemann them to be away from their parents. will miss some school and at least one parent has to take also need to help the family understand Psychiatric hospitals also are usually not a leave from work. It’s extremely anxiety-provoking be- what might be going on, what they can comfortable working up an infection cause a normally functioning child suddenly can’t go anticipate from treatment, how to interact with each or giving intravenous treatment, which is required for to school, sleep, eat or be apart from parents, and is other and their child around the illness, and how to in- some of the immune therapies used for this disease, so involved in rituals and tics. Another thing that’s very teract with the child’s school. the children’s medical needs can’t always be met in a disruptive is trying to find someone who will provide Unfortunately, a lot of the tools in psychiatry are psychiatric setting. medical and psychiatric care for your child. How do medications — for OCD, depression, ADHD, tics — Often, there is no place other than home to treat you find someone if providers say “I don’t believe in it” that don’t work the same way on an acutely inflamed children with PANS/PANDAS, which can be really or “I don’t know how to treat this”? nervous system as they would on garden-variety, idio- hard on the family. Ideally, for the future, I see a day pathic childhood mental illnesses. When medications when we have med-psych units for these patients in Why were the PANS/PANDAs treatment guidelines are used, usually for residual symptoms, the guidelines the same way that we now have excellent med-psych 2 needed? suggest beginning with one-fourth of the typical start- units for eating disorders. We would need hospital staff THIENEMANN: Right now, there isn’t enough solid, em- ing dose of medication and increasing the dose very who specialize in addressing the psychiatric problems pirical evidence to say definitively “this is what you do” slowly. There can be complex interactions between and family stress that go along with PANS/PANDAS, for these patients. For some aspects of treatment we medications, and between the medications and other as well as people who can diagnose and treat the more have evidence, but overall we have to bridge the gap changing variables related to where a child is in the ill- traditional medical problems. between our current clinical experience and knowledge, ness and concomitant treatments. It makes treatment and the clinical studies. We are continuing to collect complicated. What other changes do we need next for PANS/ evidence, but many children will be identified with 5 PANDAs patients? PANS/PANDAS before that work is complete. Physi- What are some of the gaps in how our health care THIENEMANN: Early identification. When someone cians and other professionals need to know what to do 4 system is set up to treat these children? comes to their doctor with sudden behavioral change, for them now. THIENEMANN: Unfortunately, we lack a good place to emotional change, suddenly has tics or suddenly stops Also, despite the fact that we published diagnostic hospitalize these kids. eating, this disease should automatically be on the dif- guidelines for PANS/PANDAS in 2015, I think some If we put them in a pediatric hospital when they’re ferential diagnosis. If we identify it early, it’s less com- physicians still feel it’s not legit. We want physicians to unpredictably agitated or rageful, it doesn’t work. Pe- plicated to treat and the patients have better outcomes. take this disease seriously and, even more importantly, diatric hospitals are not set up for kids who may run ISM

Baseline an ill state during the course of the study. And this tran- All Project Baseline study data will be hosted on the continued from page 1 sition may look different in different Google Cloud Platform, with great con- ethnic groups or genders.” sideration for data safety, privacy and se- able participant in the longitudinal study; as a breast Like Purchase, participant Camilo curity. In the future, de-identified data cancer survivor and a woman, her biological data could Barcenas, 39, is eager to contribute his will be made available to qualified re- provide important information for researchers seeking health data to the landmark study. “This searchers for exploratory analysis such as to understand the murky border between health and is a unique time in history,” said Barce- characterizing the variation of the par- disease. nas, a health care technology entrepre- ticipants and identifying biomarkers of The study is the first initiative of Project Baseline, neur who identifies as Hispanic and disease-related transitions. which is a broader effort to establish a well-defined has two young children. “We have the “This study is highly unique in the baseline of human health, as well as a rich data platform capability to collect lots of information depth of information it gathers about that may be used to better understand the transition about individuals and to analyze that individuals over time,” said Gambhir, from health to disease. Recruitment at Stanford began data in a quantitative way to learn even who is also the director of the Canary in June and is ongoing. more about ourselves as a species and to Center for Cancer Early Detection at Wide range of participants needed use that knowledge for the betterment Sanjiv Sam Gambhir Stanford. “We want to encourage any- of humanity.” one interested — particularly under- “It’s important that we enroll a broad spectrum of Participation in the study involves a represented minorities, the elderly and participants, from those who are healthy to those who two-day visit to Stanford, during which participants’ those at high risk for cancer or cardiovascular disease — have a higher-than-normal risk for cancer or cardiovas- health histories and vital signs are assessed and biospeci- to visit the website to learn more about the study and cular disease,” said professor and mens such as saliva and blood are apply to participate.” chair of radiology Sanjiv Sam collected. Clinical tests such as “Once you truly understand what the study is at- Gambhir, MD, PhD, the study’s “It’s important that we echocardiograms, CT scans and tempting to accomplish,” said Purchase, “it almost feels principal investigator at Stanford. enroll a broad spectrum chest X-rays are conducted, and like a moral obligation to participate. My youngest “We also need people of all ages participants are given an investi- daughter is a brain cancer survivor and a huge motivat- and ethnic backgrounds. The of participants.” gational study watch and a sleep ing factor for me. Between my breast cancer and her reason that this is so important is sensor to measure their activity brain cancer, we are desperate to move medical knowl- that we want to capture the tran- levels and sleep patterns. After the edge forward.” sition from health to illness at a molecular level. Enroll- initial visit, participants respond to regular surveys via People interested in participating in the study should ing people at higher risk can increase the probability a smartphone, computer or call center, and return to visit www.projectbaseline.com or call 855-5-BASE- that we will observe study participants transitioning to Stanford at least once a year for further data collection. LINE (855) 522-7354. ISM INSIDE STANFORD MEDICINE NOVEMBER 6, 2017 7 BioSci Careers expands programs to prepare trainees for range of jobs

By Tracie White The changes at the career center were spurred in part cent of all respondents were pursuing nonacademic ca- by studies showing that biosciences graduates are in- reers. About 30 percent were working in biotechnology. BioSci Careers, formerly known as the School of creasingly taking nonacademic jobs. A recent study by Other areas of work included government, consulting Medicine Career Center, is marking its 15th anni- the National Institutes of Health showed that almost 80 and finance. versary by expanding its services to meet the evolving percent of research-trained professionals in biomedicine BioSci Careers assists more than 2,000 trainees per needs of students and postdoctoral scholars. nationwide are employed outside academia. At Stan- year in identifying and preparing for future careers in BioSci Careers, which describes itself as a “career ford, those numbers aren’t quite so dramatic, but they’re academia, health care, biotechnology, entrepreneurship, community,” has added new courses in law, public pol- trending in that direction, Eberle said. data science, education, nonprofit organizations, gov- icy, consulting, business, finance and communication Alumni survey results ernment, law, finance, government policy and science as part of an effort to help trainees learn how they can communication, Eberle said. transfer their skills to other professions, said Stephanie A survey of Stanford alumni with PhDs in the bio- “We’re here to help trainees make good career deci- Eberle, assistant dean of BioSci Careers. sciences found that a majority are pursuing careers sions based on fact and self-awareness rather than as- “It’s not easy for our trainees to make the transition outside academia, a major shift over that past decade, sumptions and fears,” Eberle said. “Our goal is to help from school to careers,” Eberle said. “Often, they don’t Eberle said. trainees develop their many transferrable skills.” know how to market themselves. They’ve been so fo- The survey examined career trends for biosciences More information is available at bioscicareers.stan- cused on one particular facet of science.” alumni between 2010 and 2015 and found that 52 per- ford.edu. ISM

man brain development and examining of note the mechanisms of neuropsychiatric dis- Stanford receives grant to create center orders. Scherrer, one of three neurosci- reports on significant honors and awards for faculty, staff and students ence investigators getting the award, is for support of cancer immunotherapy working to eliminate the brain’s interpre- tation of pain as unpleasant and identify The School of Medicine is one of ELIZABETH EGAN, MD, PhD, assistant new ways to treat pain more efficiently four institutions to receive a grant professor of pediatrics and of microbi- and safely than currently done with from the National Cancer Insti- ology and immunology, will receive a opioids. tute to establish a Center for the 2018 Young Investigator Award from COURTNEY PEDERSEN, MARGOT ROBIN- Immune Monitoring and Analy- the American Society for Microbiology. SON and HANNAH WILD, who are medical sis of Cancer. Together, the centers The honor, which includes a travel sti- students at Stanford, were awarded 2017 will form a network of laboratories pend, recognizes early career scientists Benjamin H. Kean Travel Fellowships in to support adult and pediatric im- for research excellence and potential in Tropical Medicine from the American munotherapy trials by analyzing the fields of microbiology and infectious Society of Tropical Medicine and Hy- patients’ immune phenotype and disease. She is studying the role of the giene. The fellowship provides airfare function and performing deep tu- Holden Maecker Sean Bendall human erythrocyte in host susceptibility and $1,000 in living expenses for clinical mor profiling. to malaria. training or a research project in an area The grant provides the Stanford cen- at Mount Sinai and the MD Anderson SHANE LIDDELOW, PhD, a research affected by tropical diseases. Pedersen’s ter approximately $12.5 million over Cancer Center at the University of Texas. scientist in neurobiology, and ANCA project examined the prevalence and im- five years. It will be headed by Holden The grants were announced by the PASCA, MD, a postdoctoral scholar in pact of atopic diseases among children Maecker, PhD, professor of microbiol- National Cancer Institute as part of its neonatology, were named 2017 STAT under the age of 5 and their families in ogy and immunology, and director of the $215 million Partnership for Accelerat- Wunderkinds by STAT News, an online rural Bangladesh. Robinson’s project Stanford Human Immune Monitoring ing Cancer Therapies effort, which is a biomedical news organization. Liddelow evaluated pediatric tuberculosis screen- Center; and Sean Bendall, PhD, assistant public-private collaboration between examines the role of astrocytes in central ing strategies in a community with a professor of pathology. the National Institutes of Health and nervous system injury and neurodegen- high TB rate in South Africa. Wild trav- Other recipients of the CIMAC 11 biopharmaceutical companies. The erative disease, with the goal of develop- eled to Ethiopia’s remote Omo Valley to grants are the Dana-Farber Cancer In- partnership is part of the NIH’s Cancer ing new therapies. Pasca has developed a design and test methods for monitoring stitute, the Icahn School of Medicine Moonshot. ISM model of a preterm brain to study neu- the health status of nomadic pastoralists. rodevelopmental problems in preterm JOHN RATLIFF, MD, was promoted to babies. professor of neurosurgery, effective July SERGIU PASCA, MD, assistant profes- 1. His research focuses on quality im- sor of psychiatry and behavioral sciences, provement, decreasing complications trition. The award honors society mem- progression with the goal of developing and GREGORY SCHERRER, PhD, PharmD, in spine surgery and improving surgical bers who have made major contributions therapies. assistant professor of anesthesiology, treatment of intramedullary spinal cord to the field. He investigates the spatio- WILLIAM WEIS, PhD, the William M. perioperative and pain medicine and of tumors. He is the vice chair of neurosur- temporal regulation of genes expressed in Hume Professor, professor and chair of neurosurgery, were named 2017 New gery and co-director of the Division of the intestine and associated with nutrient structural biology and professor of pho- York Stem Cell Foundation Robertson Spine and Peripheral Nerve Surgery. assimilation. ton science and of molecular and cellu- Investigators. The awards, which include MAYA ROSSIN-SLATER, PhD, was ap- MANJULA TAMURA, MD, was promoted lar physiology, and GEORGIOS SKINIOTIS, $1.5 million in seed funding for each re- pointed assistant professor of health re- to professor of medicine, effective Aug. PhD, professor of molecular and cellu- cipient, recognize early career scientists search and policy, effective Sept. 1. Her 1. Her primary interest is in improving lar physiology and of structural biology, whose innova- research interests include maternal and the quality of end-stage renal disease were named Innovation Fund Investiga- tive research has child well-being, family structure and be- care among older adults. Her work aims tors by the Pew Charitable Trusts. This the potential to havior, and policies targeting disadvan- to describe outcomes in older patients new program promotes collaborative lead to improved taged populations in the United States and to compare the effectiveness of dif- research between alumni of the Pew therapies. Pasca, and other developed countries. ferent management strategies on these scholars and fellows programs. Each one of three stem ERIC SIBLEY, MD, PhD, associate pro- outcomes. partnership award provides $200,000 cell investigators fessor of pediatrics and assistant dean for CAPUCINE VAN RECHEM, PhD, was ap- over two years. Weis and Skiniotis plan to receive the academic advising, received the 2017 pointed assistant professor of pathology, to determine the 3-D structure of a sig- award, develops Distinguished Service Award from the effective Sept. 1. Her work focuses on naling complex in the Wnt pathway, new approaches North American Society for Pediatric understanding the effects of chromatin which is involved in cellular develop- ISM Elizabeth Egan for studying hu- Gastroenterology, Hepatology and Nu- modifiers on cancer development and ment and cancer.

Shane Liddelow Anca Pasca Sergiu Pasca Gregory Scherrer Courtney Pedersen Margot Robinson Hannah Wild

John Ratliff Maya Rossin-Slater Eric Sibley Manjula Tamura Capucine Van Rechem William Weis Georgios Skiniotis 8 NOVEMBER 6, 2017 INSIDE STANFORD MEDICINE