The fall issue of Stanford Medicine looks at power and limits of STANFORD diagnostics. Page 4 INSIDE Volume 8, No. 21MEDICINE November 21, 2016 Published by the Office of Communication & Public Affairs Study: High-intensity statins lower mortality By Yasemin Saplakoglu RoB HYRONS / SHUttERstocK.coM atherosclerotic cardiovas- large national study has confirmed cular disease who were no the value of high-intensity statin older than 75. The ACC/ Atreatments for people with cardio- AHA guidelines differed, vascular disease, according to researchers however, from guidelines at the School of Medicine. established in 2014 by the Over the duration of a year, the re- Veterans Affairs Health searchers found that patients taking Care System, which recom- high-intensity statins had an increased mended only moderate- chance of survival over those on moder- intensity statins, noting the ate-intensity statins. The study was pub- lack of conclusive evidence lished online Nov. 9 in JAMA Cardiology. that higher-intensity statins Statins, a class of drugs that lowers are more beneficial than cholesterol levels in the blood, are com- those of moderate intensity. monly prescribed for preventing the In their study, Heiden- acceleration of cardiovascular disease reich and his team found caused by the buildup of plaque in the evidence to support the arteries, which can lead to heart attacks ACC/AHA guidelines. and stroke. They determined that Health-care providers have long de- high-intensity statins do in bated the benefits of prescribing high- fact increase rates of sur- intensity statins to their patients with vival, not only in younger cardiovascular disease. Patients, in turn, and middle-aged patients have been hesitant to take them because with cardiovascular disease, of equivocal messages from their doctors but also in a patient popu- and internet searches of patient and doc- lation not well-studied: tor perspectives. adults over 75. Conflicting recommendations “The greatest strength of this study is that we “Previously, there was definitely a used a very large, well-de- certain amount of fear on the patient’s fined clinical cohort,” said A review of more than a half-million health records showed that patients taking high-intensity statins had an increased part because most people don’t like tak- Fatima Rodriguez, MD, a chance of survival over those on moderate-intensity statins. Statins are drugs that lower cholesterol levels in the blood. ing medication,” said Paul Heidenreich, cardiology fellow at Stan- MD, professor of cardiovascular medi- ford and the study’s lead Affairs Health Care System. “This is a patients with coronary artery disease, cine and the study’s senior author. Some author. “The results show that high-in- very large patient population rich in car- cerebrovascular disease and periph- studies have shown an increased risk of tensity statins confer a survival advantage diovascular disease,” said Rodriguez. “In eral artery disease. “These are basically side effects, such as diabetes or muscle for patients with cardiovascular disease, addition to defining this large, national the three main areas affected by plaque damage, associated with higher-intensity including older adults.” patient population, we also had access to buildup — the heart, the brain and the statins. Large sample size their detailed clinical data, including co- large arteries of the rest of the body,” In 2013, the American College of morbidities and cholesterol values.” Heidenreich said. Cardiology and American Heart As- The researchers studied the medical The primary purpose was to look at Patients were taking high-intensity, sociation jointly recommended high- records of 509,766 patients across the overall patient death rates from 2013 to moderate-intensity or low-intensity intensity statin therapy for patients with country receiving care from the Veterans 2014, the researchers said. They included statins in many See STATIN, page 6 PTSD changes the brains Existence of asymptomatic Ebola of boys and girls differently confirmed in study in Sierra Leone village By Erin Digitale CYNTHIA GOLdsMITH / CENTERS FOR DISEasE CONTROL By Ruthann Richter Traumatic stress affects the brains of adolescent boys and girls differently, according to a new brain-scanning study A year after the Ebola epidemic in West Africa, from the School of Medicine. researchers from the School of Medicine and other Among youth with post-traumatic stress disorder, the institutions identified 14 individuals previously un- study found structural differences between the sexes in one known to have had the disease in a Sierra Leone vil- part of the insula, a brain region that detects cues from lage that was an Ebola hot spot. the body and processes emotions and empathy. The insula These individuals had antibodies to the virus, indi- helps to integrate one’s feelings, actions and several other cating they had been infected at one time. Yet 12 said brain functions. See PTSD, page 7 they had had no symptoms during the time of active A small number of villagers in Sierra Leone were infected with transmission in the village. the Ebola virus but reported having no symptoms, a study found. ALtaNAKA / SHUttERstocK.coM The research confirms previous suspicions that the Ebola virus does not uniformly cause severe disease, a significant portion of transmission events may have and that people may be infected without showing gone undetected during the outbreak. This shows signs of illness, said Gene Richardson, MD, a for- there was a lot more human-to-human transmission mer fellow in the Division of Infectious Diseases and than we thought.” Geographic Medicine at Stanford who is now a PhD The study was published online Nov. 15 in PLOS candidate in anthropology at the university. The find- Neglected Tropical Diseases. The study also was pre- ings also suggest that the epidemic was more wide- sented Nov. 14 at the American Society of Tropical spread than previously believed. Based on the results Medicine and Hygiene’s annual meeting in Atlanta. of the study, the researchers calculated the prevalence Richardson is lead author of the study, and Paul of minimally symptomatic infection to be 25 percent. Farmer, MD, PhD, a Harvard professor and director “The study corroborates previous evidence that of Partners In Health, is the senior author. Ebola is like most other viruses in that it causes a Testing individuals spectrum of manifestations, including minimally symptomatic infection,” Richardson said. “It pro- The research was done in the rural village of Su- vides important evidence on that front. It also means kudu in Sierra Leone, a See EBOLA, page 7 DNA sequencing determines lymphoma origin, prognosis By Krista Conger spectively enrolled patients with diffuse large B-cell germinal center subtype live for five years or more af- lymphoma. DLBCL is the most common type of non- ter diagnosis, while those with activated B-cell-like tu- Sequencing tiny bits of DNA circulating in the Hodgkin lymphoma and is highly biologically variable. mors have a poorer prognosis with current treatment blood of patients with lymphoma can accurately iden- As a result, patients vary widely in their response to regimes. These subtypes are known to predict differen- tify the cancer subtype and pinpoint mutations that treatment. About one-third of seemingly successfully tial responses to emerging targeted therapies, but they might cause drug resistance, according to researchers at treated patients eventually relapse, or their tumors be- are cumbersome to measure accurately and require the School of Medicine. come resistant to treatment. Additionally, a form of in- biopsies. This knowledge could help personalize cancer dolent B cell lymphoma, which progresses slowly with Finally, the researchers were able to predict from treatment by revealing which patients are likely to be only mild symptoms, can transform without warning the ctDNA sequences those patients whose disease was treated successfully and those who may have a poorer into an aggressive form of the disease. transforming into a much more aggressive form prior to prognosis. ‘Transformation is very difficult to detect’ the emergence of clinical symptoms, and even to iden- Tracking sequence changes over time could also tify and track specific mutations known to inhibit the provide a kind of early warning system to identify the “This transformation is very difficult to detect, and response to the targeted therapy with a drug known as emergence of an aggressive form of the cancer by pro- usually requires an invasive biopsy to diagnose,” said ibrutinib. viding a real-time window into tumor evolution. The Diehn. “Our approach will allow us to monitor patients “In this study we’ve shown five distinct ways — by findings bolster the growing notion that noninvasive, over time with a simple blood test, and may help us quantifying tumor burden, identifying disease subtype, blood-based biopsies of what’s known as circulating tu- identify transformation much earlier.” cataloging mutations, predicting transformation and mor DNA are likely to transform cancer care. The researchers used an enhanced version of a tech- providing early warnings of recurrence — that circulat- “Now we can identify the subtype of the tumor, nique they developed called CAPP-Seq to isolate and ing tumor DNA can yield potentially clinically useful watch how it changes over time and begin to tailor our sequence circulating tumor DNA, or ctDNA, from information,” said Diehn. “Now we’re eager to conduct chemotherapy choices based on the presence or absence blood samples from the patients. Unlike previous stud- prospective studies in recently diagnosed patients to of specific mutations,” said assistant professor of medi- ies, which tracked lymphoma progression by monitor- learn how we can best improve patient care.” ing the sequence of just Alizadeh and Diehn are both investigators at the MARK TUscHMAN one cancer-associated pro- Ludwig Center for Cancer Stem Cell Research and tein, CAPP-Seq can iden- Medicine at Stanford. tify a much larger range The team’s work is an example of Stanford Medi- of mutations in the tumor cine’s focus on precision health, the goal of which is to genome.