Autoimmunity, Brain & Beyond

Physician/Scientists Know What Patients Need from Bench to Bedside

 
 
Two physicians who spent the past few years doing research at the Feinstein Institute for Medical Research graduated this week with a Doctor of Philosophy (PhD) in Molecular Medicine from the Elmezzi Graduate School of Molecular Medicine. This year’s graduates are David Walter Rosenthal, DO, and Emil Pablo Nashi, MD. The program was held at the Feinstein’s Goldman International Conference Center on Thursday, May 26.

Dr. Rosenthal studied the immune responses to human papillomavirus (HPV) in the laboratory of Vincent Bonagura, MD.  Human papillomavirus causes cervical cancer and recurrent respiratory papillomatosis, a condition where benign growths form in patient’s airway.  Dr. Rosenthal’s thesis helps explain how HPV evades the normal immune response, and thereby lays the groundwork for developing a treatment for active HPV disease. 

He graduated as a Doctor of Osteopathic Medicine from the Kansas City University of Medicine and Biosciences – College of Osteopathic Medicine in Kansas City, MO.  He completed an internship and residency at St. Michael's Medical Center, Seton Hall University in Newark, NJ in Internal Medicine, dually accredited by the New England College of Osteopathic Medicine, and a fellowship in Allergy/Immunology at Albert Einstein College of Medicine’s Long Island Campus at North Shore-LIJ Health System.   He plans to pursue a career in academic medicine as a physician scientist, studying the human immune responses to viruses and other diseases affecting the immune system, such as primary immune deficiencies and HIV.

Dr. Rosenthal is the Clinical Director, Center for Young Adult, Adolescent and Pediatric HIV for the North Shore Health System and is a physician with the North Shore Medical Group in the Division of Allergy/Immunology.  He sees patients with allergies, eczema, asthma, primary immune deficiencies and HIV. 

Dr. Nashi graduated from the University of Alberta in 1998 and became interested in research during his residency. He studied lupus. After a fellowship in immunology, he completed a master’s degree during which time he studied genetic susceptibility in lupus. He worked in the Center for Autoimmune and Musculoskeletal Diseases at the Feinstein Institute. His research focuses on how signaling through a particular pathway (the B cell receptor (BCR) pathway) can contribute to autoimmunity.  He uncovered abnormalities in a particular gene called Csk that he found can alter BCR signaling. This contributes to autoimmunity in a laboratory model of lupus. The implication of this work is that the BCR pathway is important to autoimmunity, and is a potential target of therapy. Dr. Nashi is now working as a physician at the McGill University Health Center, where he is continuing his research on lupus.

The Elmezzi Graduate School of Molecular Medicine currently has 12 students enrolled. Unlike the typical graduate program at universities or medical schools, the Elmezzi Graduate School offers an individually tailored program with a strong emphasis on translational research.  

The Health System considers education a critical strategic focus.  Nine of the hospitals are teaching facilities that are involved in both graduate and undergraduate medical education.  North Shore-LIJ has partnered with Hofstra University to establish a new Medical School on Long Island.  The first class of 40 students will arrive this summer.

Daniel L. Kastner, MD, PhD, Deputy Director for Intramural Clincial Research, National Institutes for Health, and Scientific Director in the Division of Intramural Research at the National Human Genome Research Institute, accepted an honorary degree from the Elmezzi graduate program. A rheumatologist and immunologist, Dr. Kastner and his colleagues have recently played a role in identifying mutations in a gene called CIAS1 that is associated with neonatal onset multisystem inflammatory disease (NOMID). He has also conducted research on genes associated with cystinuria, the most common inherited form of kidney stones.

New recipients of endowed professorships were announced during this year’s commencement. David Battinelli, MD, is the new Betsy Cushing Whitney Professor of Medicine and Chief Academic Officer. Jeremy Boal, MD, is now The Lawrence Scherr, MD, Chief Medical Officer and Professor of Medicine. Thomas McGinn, MD, accepts the new endowed title of the David J. Greene Professor of Medicine.

A number of new professorships were also announced and include the Randi and Mark Jacobson Professor of Metabolism that was awarded to Kevin J. Tracey, MD, president of the Feinstein Institute. Peter F.R. Walker, MD, Professor of Anesthesiology went to John DiCapua, MD. The Merinoff Endowed Directorship was also awarded to Dr. Tracey.

 

 

New Protein Linked to Alzheimer’s Disease

After decades of studying the pathological process that wipes out large volumes of memory, scientists at The Feinstein Institute for Medical Research discovered that a molecule called c-Abl that has a known role in leukemia also has a hand in Alzheimer’s disease. The finding, reported in the June 14^th issue of the Journal of Alzheimer’s Disease, offers a new target for drug development that could stave off the pathological disease process.

Peter Davies, PhD, head of the Feinstein Institute’s Litwin-Zucker Center for Research in Alzheimer’s Disease, became interested in c-Abl when he found that the protein was part of the plaques and tangles that crowd the brains of Alzheimer’s patients. The protein c-Abl is a tyrosine kinase involved in cell differentiation, cell division and cell adhesion. In patients with chronic myeloid leukemia (CML), c-Abl is turned up in B cells. Inhibiting c-Abl with the cancer drug Gleevec prevents cell division. There was quite a lot known about c-Abl when Dr. Davies began thinking about its possible role in Alzheimer’s. He was looking at kinases that phosphorylate tau, the protein that accumulates inside of the neurons during the disease process.

Dr. Davies questioned whether activated c-Abl turned on the cell cycle and could kill adult cells. He designed the study to test this idea and found that turning on the cell cycle in adult brain damages the cells. In their current study, the investigators devised a clever way to activate c-Abl in neurons of normal adult mice. They turned on human c-Abl genes in two different regions – the hippocampus and the neocortex – in adult mice and discovered abundant cell death, especially in the hippocampus. “You don’t even need to count, you can just look and see holes in the cell layers of the hippocampus,” said Dr. Davies. “It is stunning. Even before the neurons die, there is florid inflammation.”

He said that the animal model is ideal for testing the benefit of drugs that turn off c-Abl. While Gleevac works in CML, it does not cross the blood-brain barrier so it would not be useful. Dr. Davies and his colleagues are looking for other drugs that inhibit c-Abl and can get into the brain. “We have a great model to test compounds for Alzheimer’s disease. Will regulating c-Abl make a difference for patients? We won’t know unless we try it in double blind clinical trials.”

            The researchers are now working to understand the mechanism of cell death. They are also investigating why males die considerably sooner than females – 12 to 15 weeks compared to 24 to 26 weeks. “It is incredibly interesting model,” said Dr. Davies. “If c-Abl is important we can learn how it works.”

            The paper detailing the findings has been published in an early online version scheduled for publication in the June 14^th issue of the Journal of Alzheimer’s Disease (http://www.j-alz.com).).

Ensuring the Safety of Radiation Therapy

Radiation oncologists took a blow in a series of front-page newspaper stories published last year on injuries that occurred nationwide in the delivery of radiation treatment. Radiation oncologists at North Shore-LIJ Health System responded to the public charge with a series of steps that will ensure that patients are protected at all points in the treatment process.

Louis Potters, MD, North Shore-LIJ’s chairman of radiation medicine, and his colleagues designed a new program that seeks to improve the quality of complex processes by identifying and removing the causes of errors, and reducing variables that increase the risk of mistakes. North Shore-LIJ has literally adjusted for complex technical challenges in the hardware and software that delivers the radiation by ensuring that nothing is rushed.

Patients do not get on the table until every step is accounted for. “We want to ensure that our patients are safe,” said Dr. Potters, who presented the pilot program recently at the American Radium Society Annual Meeting.

Just imagine all the tasks that must be in place before a patient enters the surgical suite, which is a one-time event. Planning for radiation therapy that is delivered daily for weeks requires the efforts of many caregivers, with coordinated handoffs of complex information. It is important that this happens in an aligned and controlled way, and not rushed. The safety program is specifically designed to decrease the risk of errors due to last-minute, and hurried work.

Understanding the risk for error, Dr. Potters identified all the applications that go into delivering the therapy and then set out to use the clinic as a laboratory to understand the processes. He and his colleagues basically mapped the process every step of the way. “The research was necessary to identify the appropriate processes of care, break it down into the eight key components of care and make sure every step is in place before the patient arrives for treatment,” Dr. Potters explained. He calls it the “no-fly” policy, because there will be no treatment unless every step is signed off on and ready to go. If everything is not completed on time, the appointment is pushed back.

“The classic culture is not to make patients wait,” Dr. Potters said. “But it is more important to have all the stress points in the system running smoothly to ensure minimal risk for the patient.”

Dr. Potters and his team looked at the treatment process for 520 cases in the last eight months and measured the time points to see whether the time-to-treat improved over the course of the study. And it did. “We have created this program to help mitigate risk,” said Dr. Potters. On average, 10 percent of patient appointments were pushed back. The department went from a culture of ‘just in time’ to that of ‘proactive’ recognition of a need to reschedule. And the number of “stops,” the times that an appointment had to be re-scheduled because a step in the process was not completed, also went down. During the first month of the study, they had 80 events stopped compared to 20 in the most recent month of the study.

“With complex technologies, resource-compromised staff and pressures to hasten treatment, the use of this process seems to reduce patient safety risks,” said Dr. Potters. And the patients are educated about the “no-fly” policy and are more confident that any changes made to the schedule are ultimately done to protect them.

North Shore-LIJ Radiation Medicine Department is the first in the nation to implement such a program for patient safety. “We hope that by spreading the word of how to incorporate better safety processes that other radiation oncology departments will develop similar approaches to enhance cancer care,” said Dr. Potters.

Interesting study

A Smart Ultrasound Could Save Lives: MIT and GE Work to Create One
Smart ultrasounds may eventually enable a wider range of health care providers to perform scans and make ultrasounds much more accessible in regions where healthcare services and technology are limited. Developing this smart ultrasound will be the first task at hand for GE’s new Medical Electronic Device Realization Center (MEDRC), a collaborative alliance with The Massachusetts Institute of Technology (MIT) and Analog Devices. It’s part of GE’s Healthymagination drive to reach more patients with better health care globally.
http://www.gereports.com/making-ultrasound-smarter-new-ge-mit-collab/

Sara Danzi was on this year's 18th Annual May W. Newburger Women's Honor Roll

The town of North Hempstead announced this year's honor roll of outstanding community volunteers. Among the list of 13 women is Sara Danzi, PhD, a scientist at the Feinstein Institute.   Sara Danzi, PhD, was honored for her commitment to community well beyond her laboratory research work. Sara has spent over a decade judging regional science fairs, including the Long Island Science and Engineering Fair (LISEF), Junior Science and Humanities Symposium and the Rohm and Haas Invitational Science Fair. She has also represented women in science during several career days at regional schools, including Mamie Fay School, P.S. 122 in Astoria (in association with PENCIL program,) the Manor Oaks School in New Hyde Park and the Wheatley School in Old Westbury. She has also spent a decade as a speaker for Nassau Science Explorations, an annual science symposium for high school students hosted by Hofstra University. She also lends a fundraisng hand for the Mary Brennan Inn, a soup kitchen in Hempstead. She raised $5,500 to sponsor meals at the soup kitchen in 2010. Her efforts are on-going.  Wait, there's more: Sara is a Board Member of the New Hyde Park Runner’s Club. Proceeds from the organization's annual race benefits the community.  She also participates in Bicycle Safety Day (2009-2011) and lends a hand at the Ronald McDonald House. She has also spent several years fundraising for Beadforlife, an organization to support women in poverty in Uganda.

Sara Danzi studies the relationship between thyroid hormone and cardiovascular disease. Her friends and colleagues are very proud of her work -- at work and in her community of North Hempstead. 

Approval of new Lupus drug, Benlysta, studied at the Feinstein

There are many labs at the Feinstein Institute that study Lupus, including a Clinical Trials Unit that has several experimental studies going on. You can get more information on the lupus work going on at the institute by going to www.feinsteininstitute.org and going to the Diamond laboratory.

http://online.wsj.com/article/SB10001424052748703453804576191024114240558.html

 Other doctors were similarly cautious. "We're going to have to see just where this is going to fit" in how we treat lupus patients, said Betty Diamond, head of the Center of Autoimmune and Musculoskeletal Diseases at the Feinstein Institute for Medical Research, Manhasset, N.Y.

She noted that many patients in the studies were able to reduce their use of steroids. "If that bears out over the long haul, that would be very good," said Dr. Diamond.

http://www.google.com/hostednews/ap/article/ALeqM5i6UD2-j6FHQQL889CI9u8UtNzwiQ?docId=8fee2943d0c34655a011f59cca8606fd

Dr. Betty Diamond, who has studied lupus for 30 years, said Benlysta should provide encouragement to researchers and drug developers.

"It will send out the message that it's possible to conduct a successful clinical trial in lupus and that's tremendously important to keep the pharmaceutical industry interested in this disease," said Diamond, a researcher at the Feinstein Institute in New York

http://abcnews.go.com/Health/Wellness/fda-poised-approve-lupus-drug-50-years/story?id=13093783

"We still have a long way to go in understanding and treating lupus, but it's important to approve this right now. It really is the first drug for lupus to meet clinical endpoints [in decades]," says Dr. Betty Diamond, a lupus researcher who heads the Center for Autoimmune and Musculoskeletal Diseases at the Feinstein Institute.

 http://www.latimes.com/health/la-na-lupus-20110310,0,5507004.story

One of Benlysta's benefits is that patients can use less prednisone, a steroid used to control symptoms, said Cynthia Aranow, co-director of autoimmune diseases and clinical research at the Feinstein Institute for Medical Research in Manhasset, N.Y.

Here is an announcement from the Lupus Foundation of America:

Lupus Foundation of America Applauds FDA Decision to Approve BENLYSTA®

First New Treatment for Lupus More than 52 Years

(Washington, DC, March 9, 2011) Today, the U.S. Food and Drug Administration (FDA) approved the drug, BENLYSTA®, for the treatment of lupus, an autoimmune disease.

Sandra C. Raymond, President and Chief Executive Officer of the Lupus Foundation of America (LFA), has issued the following statement regarding the FDA’s decision:

"This is a historic day for the millions of people with lupus and their families around the world who have waited more than 52 years for a treatment breakthrough for lupus. We at the LFA applaud the FDA’s decision to approve BENLYSTA®. BENLYSTA is the first drug ever to be specifically developed to treat lupus, and is a significant first step toward reaching our goal of developing an arsenal of new, safe, effective, and tolerable treatments. Today marks the beginning of a new era of improved diagnosis, prevention, and treatment for the disease.

"The LFA wishes to thank the physicians, researchers, industry leaders, and the many study volunteers who made this day possible. We also extend a special thank you to BENLYSTA’s developers, the staff of Human Genome Sciences and GlaxoSmithKline, who have long been committed to the research and development process. These efforts will go a long way in elevating the profile of this disease that remains a significant national public health problem.

"There are a number of pioneering biotechnology and pharmaceutical companies, involved in the research and development of new treatments for lupus, and our hope is that today’s decision will further stimulate additional companies to invest in new therapies for lupus. To build on this momentum and encourage the development of new treatments, the LFA has launched new initiatives that help to strengthen clinical trials. These programs include the launch of a Web-based program designed to train clinical investigators on the instruments used in trials. As well, the LFA recently implemented the LFA Lupus Research Registry which enables individuals to be notified about new clinical trials in their geographic area. The Registry is part of the LFA’s Center for Clinical Trials Education.

"The LFA also is partnering with key stakeholders from industry, government, and the scientific community to evaluate data from previous lupus clinical trials with the goal to improve the design of future studies."

About the LFA’s National Research Program

The LFA’s National Research Program: Bringing Down the Barriers™, is dedicated to addressing research issues that have for decades obstructed basic biomedical, clinical, epidemiological, behavioral, and translational lupus research. The LFA’s approach to research is unique because it directs its funding to areas of research where gaps exist in the understanding of lupus, and to promising areas of study in which other public and private organizations have not focused their efforts. Using a three-pronged strategy, the LFA and its national network are committed to advancing the science and medicine of lupus by: directly funding research to close the gaps in lupus research; advocating for expanded investment in research from public and private sources; and leading special initiatives and forging collaborative efforts among stakeholders to address critical issues to advancing the science and medicine of lupus. For more information about the LFA’s National Research Program, visit

# # #

Here is an announcement from the Lupus Research Institute:

Lupus Research Institute Welcomes First New Treatment Approved For Lupus in More Than 50 Years

The Lupus Research Institute (LRI) and its National Coalition of state and local lupus organizations welcome the U.S. Food and Drug Administration’s (FDA) historic approval of BENLYSTA® (belimumab) for systemic lupus erythematosus (lupus), launching the first safe and effective treatment for lupus in more than half a century.

“This is a moment of enormous relief for people with lupus, and a landmark achievement for the nation’s scientists, doctors and industry investigators searching for new answers to lupus,” said Margaret G. Dowd, president of the Lupus Research Institute, an organization uniquely dedicated to pioneering discovery through novel research in lupus. “Benlysta’s winding path to FDA approval is a triumph for the dedicated pursuit of innovative science and smart trial design in achieving solid results in the complex autoimmune disease of lupus.” 

  
The FDA announced today that BENLYSTA, developed by Human Genome Sciences (HGS) and GlaxoSmithKline (GSK), is approved for treatment of people with active systemic lupus. This decision followed its Arthritis Advisory Committee’s 13-2 vote on November 16, 2010 to recommend the drug’s approval. 

 
The development of BENLYSTA stems from the scientific discovery of a new immune system molecule, BLyS, which revealed a critical new pathway that can be manipulated to treat lupus.  Benlysta is founded on novel, fundamental science from industry and academia that explores a range of disease pathways and mechanisms, much like the studies that the LRI has been supporting for a decade.

“With BENLYSTA, physicians can now prescribe an effective new agent to manage the signs and symptoms of lupus, and improve the quality of life of their patients,” said David S. Pisetsky, M.D., Ph.D., Professor of Medicine and Immunology at Duke University Medical Center and a member of the LRI Scientific Advisory Board.

 
“Furthermore, the approval provides important lessons for the lupus research field,” said Dr. Pisetsky. “The trial design of the BENLYSTA studies, including the use of a composite outcome measure to assess efficacy, is a major innovation. The developers have taken a new pathway for drug research in lupus, which hopefully, will encourage other companies to rededicate themselves to innovation to reduce and eventually wipe out the burden of this serious autoimmune disease.”

“The approval of BENLYSTA means good news for patients like me, hopefully reducing the seemingly endless number of medications with harsh side effects we need to take to stay alive,” said Sabrina Nixon, an author and single mother of two from Chicago who was diagnosed with lupus in 2004.

"We thank the hundreds of people with lupus who enrolled and took part in these important BENLYSTA trials," said Dowd. The LRI assists in educating people with lupus about participating in clinical trials to bring safe and effective treatments to market.  To learn more, visit www.LupusTrials.org.
 

 

Doctors Listen to End of Life Concerns

Physicians are trained to save lives but just how good are they at letting their patients go?

 

That is the question that researchers in the Department of Population Health at North Shore-Long Island Jewish Health System addressed in a study designed to test an intensive end-of-life training intervention on 150 residents and fellows. The scientists set out to see if such instruction could lead to more sensitive conversations about these issues with patients.

 

“It is one thing to know about the details of advanced directives but, in our rapidly aging society, a good doctor has to know how to talk to patients about how they want to be treated at the end of life,” said Renée Pekmezaris, PhD, vice president of health services research in the Department of Population Health.

 

Dr. Pekmezaris and her colleagues tested the intervention on 150 residents and fellows to see whether the training influenced the care that they delivered. At the end of the study, they found that physicians-in-training were much more sensitive to talking about end-of-life issues and said that they felt more comfortable “in providing peace for dying patients.”

 

When residents and fellows are asked why they entered medicine there is a shared value to help patients. And as many come to know when they start caring for terminally ill patients it is not always a matter of helping them to live. “We need to help them to die well, too” said Gisele Wolf Klein, MD, a geriatrician at Long Island Jewish Medical Center and one of the study investigators.

 

As part of the training, these newly minted physicians review the literature on the “good death.” They come to understand the reasons why so many older people do not have advanced directives. Even in advancing age, people do not feel there is an urgency to make their wishes known. They think that they can count on their loved ones to make those types of decisions. But studies have shown that a person’s health care proxy is only accurate 50 percent of the time when they are faced with an emergency situation. Does their loved one want to be resuscitated? And if so, under what circumstances?

 

Enter the physician. His or her job is to help patients, but how comfortable are they in starting a discussion about end-of-life concerns? How do they begin? How long will it take? What if it becomes too uncomfortable? When is it appropriate to begin such a conversation?

 

During the training, the 150 doctors learned how to administer Medical Orders for Life-Sustaining Treatment (the MOLST form) and spent a lot of time role playing a variety of end-of-life situations when they would have to engage the patient or their family into the “good death” talk. Dr. Lori Katinas, who led the role-playing sessions, said, “It was clear just how much these young doctors struggle to do right by the patient, and that they needed help in how to effectively have these conversations.”

 

To compare the effectiveness of the training, the scientists reached out to residents and fellows in nearby medical centers to ask the same kinds of pre and post survey questions. An analysis of responses among all study volunteers was conducted.

 

Were the doctors who went through the intensive training actually more comfortable and better at talking to patients about end-of-life care?

 

According to Dr. Pekmezaris, they were. “The doctors who were trained said that they felt it was much easier to communicate with patients.” They also felt more at ease with administering the MOLST form. And ultimately, said Dr. Pekmezaris, “being able to talk to patients helps them understand what medical interventions patients want. It is important for everyone (including health care proxies) to feel comfortable in these discussions.”

 

Many states, including New York, have individualized medical orders for advanced directives for life-sustaining treatment that can now be added to the patient chart. These orders are built on understanding how the patient wants to live and die. The orders include documenting patient wishes about cardiopulmonary resuscitation, medical interventions, artificial nutrition and antibiotics. It is a way to clearly specify the interventions that are acceptable in the throes of a chronic, life-threatening illness.

 

The study was published in Gerontology and Geriatrics Education.

Perinatal Safety Initiative Reduces Adverse Obstetrical Outcomes

Having a child is a life event that is equal parts magic and fear. Will the baby be healthy? Will labor and delivery pose challenges? Are there ways to reduce the risk for adverse events? Hospital obstetrical units face these questions round-the-clock.

 

To increase the chances of a safe labor and delivery, and make way for a memorable birthing experience, the North Shore-LIJ Health System has launched a new prenatal quality initiative, led by Adiel Fleischer, MD, chair of obstetrics and gynecology at North Shore University Hospital and Long Island Jewish (LIJ) Medical Center, and Brian Wagner, MD, a maternal-fetal medicine specialist.

 

They designed and implemented a two-year comprehensive training program for all staff in the obstetrics wings at North Shore University Hospital and LIJ Medical Center. Staff was required to complete the formalized training that included evidence-based protocols to reduce adverse events.

 

These protocols included competency in reading electronic fetal heart rate monitors, communication skills and problem solving on a wide range of high-risk obstetrical emergencies through simulation programs. The hope was that the obstetrics initiative would lead to fewer adverse outcomes for mother and child.

 

It worked.

 

A team of scientists in the Division of Health Services Research in the health system’s Department of Population Health analyzed almost a dozen adverse outcome measures and found that such problems, including returning to the operating room and birth trauma, were significantly reduced by more than half – from two percent to 0.8 percent. Data also showed better outcomes were maintained over the two-year study period.

 

The analysis was published in the March issue of the Journal for Healthcare Quality.

 

In addition to improved outcomes, staff perceptions of safety improved significantly, as did perceptions among new mothers, who reported that their obstetrics teams were more cooperative and hard-working. What’s more, there were improvements in the documentation of abnormal fetal heart rate tracings and obstetric hemorrhage.

 

“The importance of the study and its long-term impact is that the safety measures that we introduced have provided better communication among the various healthcare providers. There is earlier identification of at-risk patients and team approach to patient care is critical to patient care,” said Dr. Fleischer.

        

Kenneth Abrams, MD, senior vice president of clinical operations and chief quality officer at the North Shore-LIJ Health System, agrees. “We improved patient safety and enhanced both staff and patient experience,” said Dr.Abrams. “This initiative shows that we can reduce adverse events and enhance a culture of safety.”

 

North Shore-LIJ hospitals deliver more than 21,000 babies every year, which represents nearly 10 percent of all births in New York State. Following the national trend to identify problems in the delivery of healthcare and reduce medical errors, clinicians implemented internal and external reviews of sentinel events, which included examinations of monthly obstetric charts. The chart reviewers looked at the documentation and management of obstetric hemorrhage and abnormal fetal heart rate tracings. The review led to a comprehensive list of potential causes of adverse events, including an inadequate escalation policy, and lack of standard protocol and standardizations pertaining to the interpretation for fetal heart rates. These factors are thought to play an important role in adverse outcomes.

 

As part of the program, Dr. Fleischer and his colleagues introduced multidisciplinary teaching rounds to help foster communication. During these daily meetings, the perinatal team reviewed and discussed appropriate assessment and management of obstetrical admissions. They enhanced the electronic medical record and implemented new protocols that have been shown to reduce the risk for adverse events.

 

Patients were contacted after they left the hospital and asked to complete a questionnaire about their experience during labor and delivery. Staff perceptions of safety were also assessed before and after the program.

 

“A critical component of the initiative was the educational process designed to improve recognition, appropriately document complications and avoid interventions that increase the risk of complications,” the researchers wrote in the journal. The study was led by Renee Pekmezaris, PhD, vice president for community health and health services research in the North Shore-LIJ Department of Population Health.

 

Watch Feinstein scientists talk about latest discovery on human B1 immune cells

Researchers Discover Innate B Cell in Humans that Protects Against Infections

It has long been thought that the human body contains innate immune defense B cells that are present from birth, even before immunization or exposure to infectious organisms. But the question has always been where might these cells be?

Immunologist Thomas L. Rothstein, MD, PhD, and his colleagues from The Feinstein Institute for Medical Research have staked their reputations on finding these so-called “B1 cells” that make “natural” protective antibodies and come online before the adaptive immune system is mature enough to start working. And that is precisely what they have done.

After many years of research, Dr. Rothstein’s team of investigators from the Feinstein Institute has found this unique population of B1 cells, which were hiding in plain sight. It seems that they reside among the same population of B cells that are built one by one when the body comes in contact with millions of infectious bugs over a lifetime – so-called adaptive or memory B cells.  The key was finding the particular markers that differentiate B1 cells from every other B cell type. The results of the study were published in the Journal of Experimental Medicine this week.

“The identification of human B1 cells provides a foundation for future studies on the nature and role of these cells in human disease,” the scientists wrote in the study. The lead author, Daniel Griffin, MD, gave up his private physician practice to work toward a doctoral degree in molecular medicine. At any one time, the Feinstein Institute trains about 10 physician-scientists enrolled in the Elmezzi Graduate School of Molecular Medicine. When Dr. Griffin arrived two years ago, Dr. Rothstein laid out several research options. Dr. Rothstein, head of the Feinstein’s Center for Oncology and Cell Biology, told Dr. Griffin about the hunt for human B1 cells, but knew that it would be a big gamble to undertake an uncertain thesis project that may never pan out.

Dr. Griffin didn’t see it that way. He eagerly accepted the challenge and designed a project that he hoped would bear the fruit of the human B1 cell. Several things were in his favor. The Feinstein Institute, through its Tissue Donation Program, provides human blood samples to investigators for research, including umbilical cord blood. Secondly, the Feinstein Institute helped Dr. Rothstein’s lab purchased an expensive piece of equipment that sorts cells. If the B1 cells were present and different enough from memory B cells, the cell sorter would separate the two populations. Then, Dr. Griffin and his colleagues could do the lab work to figure out the nature of the cell populations and whether there really is a human B1 cell.

There was enough evidence from animal studies to suggest that human B1 cells exist. Dr. Rothstein and his colleagues had spent two decades studying mouse B1 cells, so there was a lot of historical information already in place. The big question that generated heated debate was whether innate B1 cells in the mouse exist in humans.  In the mouse, CD5 is a good marker for B1 cells. The marker readily distinguishes between mouse B1 and B2 cells.  But CD5 is not a good marker for human B1 cells because it is present on many different human B cell types. With the continued inability to identify human B1 cells, scientists began to doubt whether B1 cells exist in humans.

It was against this background that Dr. Griffin, Nichol Holodick, PhD, and Dr. Rothstein undertook a counterintuitive quest to identify human B1 cells. They knew what B1 cells do in mice, so they decided to define a set of functions based on previous work in the mouse system and then ask what B cells in humans carry out these very same functions. In mice, B1 cells secrete antibodies stimulate T cells and are continually signaling. Dr. Griffin began collecting blood samples and running them through the cell sorter. He used fluorescent antibodies to help identify different populations of B cells. In time, he found something rather surprising -- a certain percentage of B cells were expressing a marker, CD27, normally seen in so-called memory or adaptive B cells. It turned out that the mysterious population of innate B1 cells was hiding out among the B cell population that is generated in response to vaccination and exposure to infectious agents.  But the B1 cells also contained a special marker, CD43, that distinguished them from memory B cells and, in fact, from all other B cells.  So by these two distinct markers, CD27 and CD43, human B1 cells can be recognized and studied, and they turned out to have functional characteristics similar to mouse B1 cells.

“Scientists have known that there were protective naturally occurring antibodies in humans but we didn’t know where they were coming from,” said Dr. Rothstein.

Aside from their role in providing an antibody shield against infectious organisms,  the antibodies produced by B1 cells help dispose of unwanted cellular debris which, if not removed, can be toxic.  In this way, it is speculated that B1 cells may help to counteract heart disease, cancer and neurodegenerative conditions.  The Rothstein group has already shown that the number of B1 cells declines with advancing age, which raises the possibility that the loss of B1 cells may contribute to these diseases of the elderly.  Most importantly, they will now work to develop treatments to enhance B1 cell numbers, or to provide therapeutic antibodies derived from B1 cells, in order to bolster the normal function of these newly found human B1 cells.

Feinstein Scientists Identify Better Way to Treat Auto-Immune Hearing Loss

 Scientists at the Feinstein Institute for Medical Research have figured out why some patients with hearing loss triggered by an autoimmune response do not respond to the traditional therapy. Using this marker, scientists may be able to identify those patients who would best respond to treatment. The finding appears this month in the Journal of Immunology.

Andrea Vambutas, MD, is a neurotologist who conducts research on autoimmune inner ear disease (AIED), a condition that is not well understood and difficult to diagnosis. When AIED is suspected, patients are given oral steroids (during periods of acute hearing loss) but only half respond to the medication and recover some hearing. When patients are not responsive to steroid therapy, the clinicians may turn to other causes of hearing loss, thereby shutting the door on the possibility of an autoimmune condition.

Dr. Vambutas and her colleagues set out to find biomarkers of AIED that would help in making a definitive diagnosis. They collected inner-ear fluid in patients undergoing cochlear implant surgery and identified a decoy receptor, a protein that sequesters inflammation. Those patients with AIED could not prevent inflammation. “If people who show a response to steroids had evidence of increased decoy receptor production, we could use this technique to see who might respond to steroids,” said Dr. Vambutas. Indeed, they found that AIED patients who clinically respond to steroids correlated with the ability of patients' immune cells to make this decoy receptor in response to steroids in culture. 

Interleukin-1 Receptor Type II (IL1R2) is the molecular decoy that traps interleukin-1β (IL-1β) and does not initiate subsequent signaling events, thereby suppressing an inflammatory response. IL1R2 expression is induced by the steroid dexamethasone. Her laboratory has recently identified that aberrant expression of interleukin-1, an inflammatory protein, is associated with steroid resistance in these patients. 

This idea is paying off. On the basis of these findings, Dr. Vambutas and her colleagues will begin enrolling corticosteorid-resistant AIED patients for a phase I clinical trial to determine if a new medication may salvage some hearing in these patients. The clinical trial will test the benefits of an Interleukin-1 receptor antagonist called anakinra (Kineret) for the treatment of corticosteroid-resistant autoimmune hearing loss.

For more information on AIED and the clinical trial, contact Dr. Vambutas at vambutas@nshs.edu or call (718) 470-7550.