Author Interviews, Gastrointestinal Disease, Microbiome, Transplantation / 16.05.2016
Fecal Microbiota Transplantation is Promising Option for Ulcerative Colitis Treatment
MedicalResearch.com Interview with:
Dr. Sudarshan Paramsothy
University of New South Wales
Australia
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Paramsothy: This study was conducted as there is strong evidence that the gastrointestinal microbiota play a critical role in the underlying pathogenesis of inflammatory bowel disease (IBD), but treatments to date primarily are focused on controlling the associated immune response. Attempts at therapeutic microbial manipulation in ulcerative colitis (UC) to date (antibiotics, probiotics, prebiotics) have not been as impressive as one might expect. We felt intensive fecal microbiota transplantation (FMT) may be more successful than these other methods, as it involves transplanting the entire gastrointestinal microbiota from a health individual, and thus more likely to correct any underlying microbial disturbance or dysbiosis in the recipient UC patient.
Our study found that significantly more active ulcerative colitis patients treated with intensive FMT than placebo (27% vs 8%) achieved the trial primary composite endpoint of both
- clinical remission induction (ie resolution of symptoms) and
- endoscopic remission or response (ie either healing or significant improvement of the bowel lining)
Dr. Wisit Cheungpasitporn[/caption]
Wisit Cheungpasitporn, MD, Nephrology Fellow
Project mentor: Stephen B. Erickson, MD
Departments of Nephrology and Hypertension
Mayo Clinic, Rochester, MN
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Cheungpasitporn: The prevention and management of hypertension continue to be major public health challenges. Studies have shown the benefits of napping, including reduction of fatigue and improvement of alertness, mood and work performance. However, there have also been increasing reported associations between napping and cardiovascular disease, diabetes mellitus, strokes, and higher mortality from all causes. The risk of hypertension in adults who regularly take a nap is controversial.
Dr. Shipra Arya[/caption]
Shipra Arya MD, SM
Assistant Professor, Division of Vascular Surgery
Emory University School of Medicine
Assistant Professor of Epidemiology (Adjunct)
Rollins School of Public Health
Staff Physician, Atlanta VA Medical Center
Director, AVAMC Vascular Lab and Endovascular Therapy
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Arya: Peripheral Arterial Disease is the next cardiovascular epidemic. It is poorly recognized and not adequately treated compared to heart disease – and research is lacking on the optimal use of statins for PAD patients. Very few randomized clinical trials have been done specifically in PAD patients to assess the impact of statins on cardiovascular outcomes and none on limb related outcomes. The 2013 ACC/AHA guidelines for cholesterol lowering medications recommends high intensity statins for PAD patients extrapolated from the level 2 and 3 evidence and empirically based on CAD and stroke data.
In this study we looked at the amputation and mortality risk based on statin dosage in a large cohort of patients from the VA population and found that high intensity statins are associated with a significant reduction in limb loss (~30%) and mortality (~25%) in PAD patients followed by a smaller risk reduction [~23% for amputation risk reduction and 20% reduction in mortality risk] by low-moderate intensity statins as compared to no statin therapy.
Dr. Ambay Pandey[/caption]
Ambarish Pandey, MD
Cardiology Fellow, PGY5
University of Texas Southwestern Medical Center
Dallas, Texas
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Pandey: Previous studies have reported an underutilization of guideline based heart failure therapies among patients with heart failure (HF) and end-stage renal diseases. However, it is not known if the proportional use of these evidence-based medical therapies and associated clinical outcomes among these patients has changed over time. In this study, we observed a significant increase in adherence to heart failure process of care measures over time among dialysis patients with no significant change in clinical outcomes over time.
Dr. Meghan Azad[/caption]
Meghan Azad PhD
Assistant Professor, Department of Pediatrics & Child Health and Community Health Sciences
University of Manitoba
Associate Investigator, Canadian Healthy Infant Longitudinal Development (CHILD) Study
MedicalResearch.com: What is the background for this study?
Dr. Azad: It is well known that maternal nutrition plays a key role in “programming” fetal development and infant weight gain, but the impact of artificial sweetener consumption during this critical period has not been extensively studied. Some animal research suggests that consuming artificial sweeteners during pregnancy can predispose offspring to develop obesity, but this has never been studied in humans, until now.
Mallory Kidwell[/caption]
Mallory Kidwell, B.A.
Project Coordinator at the 
Dr. Michael McGeachie[/caption]
Michael McGeachie, PhD
Instructor in Medicine
Harvard Medical School
Channing Division of Network Medicine
Brigham and Women's Hospital
MedicalResearch.com: What is the background for this study?
Dr. McGeachie: In asthma, and in general but particularly in asthma, a person’s level of lung function has a big impact on his or her quality of life, level of respiratory symptoms and complications, and general morbidity. In asthma, low lung function leads to greater severity and frequency of asthma symptoms. Asthma is a common childhood illness, affecting 9-10% of children. Many children grow out of asthma as they become adults, but other asthmatics remain effected through adulthood, which can lead to a lifetime of respiratory symptoms and chronic airway obstruction, including chronic obstructive pulmonary disease (COPD).
If you consider lung function longitudinally, throughout development, plateau, and decline, different people and different asthmatics tend to exhibit different patterns of lung function. Healthy, non-asthmatic people tend to have a period of rapid lung function increase in adolescence, a plateau of lung function level in their late teens and early 20s, and starting around 25 or so a slow, gradual decline of lung function that continues throughout old age. We call this Normal Growth of lung function. However, some people exhibit Reduced Growth, where they don’t reach their expected maximum lung function for a person of the same age, sex, height, and race. Others can show Early Decline, who might reach a normal maximum but then begin to decline immediately without a plateau or with a truncated plateau. We hypothesized that these patterns, Reduced Growth and Early Decline, might have different baseline indicators, precursors, outcomes, and risk of developing COPD.
Dr. Geoffrey Liu[/caption]
Dr. Geoffrey Liu, MD MSC
Princess Margaret Hospital/Ontario Cancer Institute
University of Toronto
Toronto, Ontario
Canada
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Liu: Cetuximab is a monoclonal antibody therapy used in metastatic colorectal cancer patients when other chemotherapy options have been exhausted. Currently, the only useful biomarker to determine whether metastatic colorectal cancer patients will benefit from the drug, cetuximab, is whether patients carry a RAS mutation in their tumours. We evaluated additional biomarkers using samples from a Phase III clinical trial led by the Canadian Cancer Trials Group and the Australasian Gastrointestinal Trials Group. Our study identified a germline, heritable biomarker, a FCGR2A polymorphism, that further identifies an additional subgroup of patients who would benefit most from receiving cetuximab. This is important because the drug does have toxicity and is expensive to use; patients who are found not to likely benefit from this drug can go on quickly to try other agents, including participation in clinical trials.
Dr. Debra Silverman[/caption]
Dr. Debra Silverman Sc.D
Branch Chief and Senior Investigator in the Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology & Genetics
National Cancer Institute
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Silverman: We know that bladder cancer mortality rates have been elevated in northern New England for at least five decades. Incidence patterns in Maine, New Hampshire and Vermont are similar—about 20% higher than those for the United States overall. Elevated rates have been observed in both men and women, suggesting the role of a shared environmental etiologic factor.
A unique feature of northern New England is that a high proportion of the population uses private wells as their primary source of drinking water. The well water may contain low-to-moderate levels of arsenic. There are two possible sources of this arsenic contamination:
Dr. Gabriele Messina[/caption]
Gabriele Messina, MD Dr.PH MSc
Research Professor of Public Health
University of Siena
Department of Molecular and Developmental Medicine
Area of Public Health. Room: 2057
Siena, Italy
MedicalResearch.com: What is the background for this study?
Dr. Messina: Studies conducted in the 1970s and 1980s conferred to environmental surfaces a marginal role in the transmission of health care associated infections (HAIs). Today, it is demonstrated that several pathogens such as C. difficile, VRE (Vancomycin-resistant Enterococcus) and MRSA (Methicillin-resistant Staphylococcus aureus) can survive even for months on inanimate surfaces. Up to 40% of HAIs can be spread by the hands of doctors and hospital staff after touching infected patient and/or contaminated surfaces; furthermore, people hospitalized in rooms previously occupied by patients infected by microorganism that can persist on surfaces present an increased risk to develop HAIs.
Ms. Leigh Purvis[/caption]
Leigh Purvis, MPA
Director of Health Services Research
AARP Public Policy Institute
MedicalResearch.com Editor’s Note: The May AARP Bulletin has a important article “Black Market Meds Are Flooding the Nation’s Pharmacies And Hospitals” by Joe Eaton, discussing the growing problem of counterfeit medications entering the US pharmaceutical supply chain. Ms. Leigh Purvis of the AARP Policy Institute discussed this important issue for the readers of MedicalResearch.com. Ms. Purvis’ areas of expertise include prescription drug pricing, biologic drugs, and Medicare prescription drug coverage.
MedicalResearch.com: Is pharmaceutical theft and fraud a new or growing problem?
Ms. Purvis: I think it’s safe to say that pharmaceutical theft is a growing problem. Skyrocketing prices have made pharmaceuticals a lucrative target for criminals. Trucks transporting pharmaceuticals are a common target, although some thieves have stolen prescription drugs directly from manufacturers’ warehouses.
Pharmaceutical fraud is also a growing concern. FDA does a great deal to ensure the safety of US pharmaceuticals. However, problems can still arise, particularly when people purchase drugs online.
Dr. Shuhei Miyashita[/caption]
Dr. Shuhei Miyashita PhD
Lecturer in Intelligent Robotics
Department of Electronics
University of York, Heslington
York, UK
MedicalResearch.com: What is the background for this device? What are some of the obstacles you and your team face in the development?
Dr. Miyashita: We are developing medical technology that is less invasive and more
autonomous and thus can provide safe and consistent outcomes. The
biggest challenge is how to build a capable medical robot that is
clinically safe. Addressing this challenge requires finding
bio-compatibe materials, safe means of transportation in the body, a
way to reconfigure the robot from pill shape to unfolded shape, and
precise multi-mode control for the location and function of the robot.
Dr. Michael Miller[/caption]
Michael Miller, MD, FACC, FAHA
Professor of Cardiovascular Medicine, Epidemiology & Public Health
University of Maryland School of Medicine
Staff Physician, Baltimore VAMC
Director, Center for Preventive Cardiology
University of Maryland Medical Center
Baltimore, Maryland
MedicalResearch.com: What is the background for this study?
Dr. Miller: It has become an article of faith that HDL (the good cholesterol) is an independent risk factor for heart disease. However, previous studies did not examine the importance of HDL after accounting for both LDL (bad cholesterol) and triglycerides (blood fats). This is important because HDL is associated with LDL and triglycerides. We hypothesized that if HDL is truly an independent risk factor, then low HDL levels in isolation would continue to be linked to an increased risk of heart disease while high HDL levels would continue to protect the heart even if LDL and triglycerides levels were elevated.
Dr. Mathias Buttmann[/caption]
PD Dr. Mathias Buttmann
Senior Consultant Neurologist and Head of the Multiple Sclerosis Outpatient Clinic
University of Wuerzburg
Wuerzburg, Germany
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Buttmann: The synthetic anthracenedione mitoxantrone is approved for disease-modifying treatment of patients with aggressive forms of relapsing or secondary progressive multiple sclerosis (MS). It has been known for years that this DNA-intercalating agent increases the risk of acute myeloid leukemia. We performed a retrospective cohort study to investigate whether mitoxantrone also increases the risk for other types of malignancies. We included all 677 mitoxantrone-treated multiple sclerosis patients who were seen at our large German academic MS centre between 1994 and 2007 and collected follow-up information on the occurrence of malignancies, death and causes of death as of 2011. Follow-up was complete in 676 patients. The median age at mitoxantrone initiation was 41 years and the median follow-up duration was 8.7 years. We identified 37 patients with a malignancy after mitoxantrone initiation, among them 4 cases of acute myeloic leukemia and 7 cases of colorectal cancer.
Compared to the general population matched for sex, age and year of occurrence, we calculated an 1.5-fold increased incidence of any type of malignancy, a tenfold increased incidence of acute myeloic leukemia and a threefold increased incidence of colorectal cancer, while the incidence of other types of malignancies was not increased. Higher age at mitoxantrone initiation but neither higher cumulative mitoxantrone dose nor treatment with other immuosuppressive agents was identified as a malignancy risk factor. Fifty-five patients had died, among them 12 from a malignancy. Our study confirmed previous reports on an increased incidence of acute myeloic leukemia after mitoxantrone treatment and newly described an association between mitoxantrone therapy and an increased incidence of colorectal cancer.
Dr. Hans Hoerauf[/caption]
Prof. Dr. med. Hans Hoerauf
Direktor der Augenklinik
Universitätsmedizin Göttingen
Göttingen
MedicalResearch.com: What is the background for this study?
Dr. Hoerauf: Two treatment options, anti-vascular endothelial growth factors (anti-VEGFs) and corticosteroids, with different mechanisms of action are available for the treatment of macular edema secondary to Central Retinal Vein Occlusion (CRVO). Our study, COMRADE-C, is the first head-to-head study to investigate the clinical efficacy and safety of the European labels of ranibizumab (anti-VEGF) versus dexamethasone intravitreal implant (corticosteroid) in patients with CRVO over six months.
Dr. Katarina Truvé[/caption]
Katarina Truvé PhD
Swedish University of Agricultural Sciences and
Kerstin Lindblad-Toh
Uppsala University
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Truvé: Gliomas are malignant brain tumors that are rarely curable. These tumors occur with similar frequencies in both dogs and humans. Gliomas in dogs are strikingly similar at the biological and imaging level to human tumor counterparts. Some dog breeds such as Boxer and Bulldog are at considerably higher risk of developing glioma. Since these breeds at high risk are recently related, they are most likely carrying shared genetic risk factors. Our goal was therefore to use the dog genome to locate genes that may be involved in the development of glioma in both dogs and humans. We found a strongly associated locus and identified three candidate genes, DENR, P2RX7 and CAMKK2 in the genomic region. We have shown that CAMKK2 is lower expressed in glioma tumors than normal tissue in both dogs and human, and it has been reported that the associated canine mutation in P2RX7 results in a decrease in receptor function.
Dr. Maryam Farvid[/caption]
MedicalResearch.com Interview with:
Maryam Farvid, Ph.D.
Visiting Scientist
Department of Global Health and Population
Harvard T.H. Chan School of Public Health
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Farvid: Breast cancer is one of the most frequently diagnosed cancers and is the second leading cause of cancer deaths among women in the United States. While we know many breast cancer risk factors, few of them are easily modified. Further, evidence suggests that exposure to carcinogens and anti-carcinogens in early life may play an important role. According to this study, what women eat as teens or young adults could affect their breast cancer risk in the future. Teenage girls who eat a lot of fruits may have a lower risk of breast cancer later in life. The risk of breast cancer among women who reported the highest amount of 
Dr-Daniel Benjamin[/caption]
Dr. Daniel J. Benjamin PhD
Associate Professor (Research), USC, 2015-present
Associate Professor (with tenure), Cornell, 2013-2015
Assistant Professor, Cornell University, 2007-2013
Research Associate, NBER, 2013-present
Faculty Research Fellow, NBER, 2009-2013
MedicalResearch.com: What is the background for this study?
Dr. Benjamin: Educational attainment is primarily determined by environmental factors, but decades of twin and family studies have found that genetic factors also play a role, accounting for at least 20% of variation in educational attainment across individuals. This finding implies that there are genetic variants associated statistically with more educational attainment (people who carry these variants will tend on average to complete more formal education) and genetic variants associated statistically with less educational attainment (people who carry these variants will tend on average to complete less formal education). But none of these genetic variants had been identified until our 2013 paper on educational attainment. That paper, which studied a sample of roughly 100,000 individuals, identified 3 genetic variants associated with educational attainment, each of which has a very small effect. In the current paper, we expanded our sample to roughly 300,000 individuals, with the goal of learning much more about the genetic factors correlated with educational attainment.
Danielle Schoffman[/caption]
Danielle E. Schoffman
PhD Candidate
Department of Health Promotion, Education, and Behavior
Arnold School of Public Health
University of South Carolina
Columbia, SC 29208
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: In recent years, there has been large growth in the fast casual (e.g., Panera, Chipotle) restaurant sector, and there is a general perception among consumers that these restaurants are a healthier and fresher alternative to fast food. When we encourage participants in our research studies to reduce their fast food intake, they often ask if these fast casual restaurants also count. We were interested in looking at the calorie data for entrees at both restaurant types to see if they lined up with these assumptions.
We analyzed the calorie content of entrées at 34 fast food and 28 fast casual restaurants, and found that fast food entrées had an average of 760 calories per entrée compared to 561 for fast food entrées . Also, a greater proportion of fast casual restaurant entrées exceeded the median of 640 calories per entrée.
Dr. T. Dianne Langford[/caption]
Dr. T. Dianne Langford PhD
Associate Professor, Neuroscience and Neurovirology
Lewis Katz School of Medicine
Temple University
MedicalResearch.com: What is the background for this study?
Dr. Langford: The ocular-motor system has been shown to reflect neural damage, and one of ocular-motor functions, near point of convergence (NPC), was reported to worsen after a sport-related concussion (Mucha et al. Am J Sport Med). But the effects of subconcussive head impact, a milder form of head injury in the absence of outward symptoms remains unknown. Prior to this study, we found that in a controlled soccer heading experimental paradigm decreased NPC function, and even 24h after the headings, NPC was not normalized back to baseline (Kawata et al. 2016 Int J Sport Med). To extend our findings from the human laboratory study, we launched longitudinal clinical studies in collaboration with the Temple football team, to see if repetitive exposure to subconcussive head impacts negatively affects NPC.
Dr. Brian Boxer Wachler[/caption]
Dr. Brian Boxer Wachler MD
Boxer Wachler Vision Institute
Beverly Hills, California
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: As an eye surgeon, I observed patients tended to have more age spots on the left side of their faces. I was examining a patient with Keratoconus and after I noted her age spots on her left cheeks, I began to look into this phenomenon. It turns out there are many studies that found more skin cancer on the left side of the face compared to the right side of the face. In Australia (where people drive on the left side of the road) it’s the opposite – more skin cancer on the right side of the face. Our study found that cars on average have significantly lower UVA (ultraviolet A) protection in the side windows compared to windshields which have universally high UVA protection. I believe this can be the missing link that can explain higher rates of skin cancer on the side of the face by the driver’s window. There are also more cataracts in left eyes vs right eyes. There was no relationship between high-end cars and low-end cars for side window UV protection – in other words many more pricey cars had just as poor side window UV protection as less expensive cars.
Paul Wilmes[/caption]
Prof. Dr. Paul Wilmes
Associate Professor
Head of the Eco-Systems Biology Research Group
Luxembourg Centre for Systems Biomedicine
University of Luxembourg
Luxembourg
MedicalResearch.com: What is the background for this intestinal model?
Dr. Wilmes: Changes in the human gastrointestinal microbiome are associated with several diseases. To infer causality, experiments in representative models are essential. Widely used animal models exhibit limitations. Therefore, we set out to develop the HuMiX model which allows co-culture of human and microbial cells under conditions representative of the gastrointestinal interface.
Dr. Jaimin Trivedi[/caption]
Jaimin Trivedi, MD, MPH
Instructor
Department of Cardiovascular and Thoracic Surgery
University of Louisville
Louisville, KY 40202
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Trivedi: There is a donor heart shortage in United States and certain donor hearts are likely to be turned down because the donors required cardiopulmonary resuscitation (CPR) prior to procurement. The rationale behind conducting the study was to identify impact of donor CPR and its duration on recipient survival after transplantation.
Our findings show that presence of CPR and duration of CPR does not adversely impact the post heart transplant survival. The study also shows that ejection fraction and peak cardiac troponins between the CPR and non-CPR donors were comparable at time of transplant suggesting recovery of cardiac function.
Dr. Erica Spatz[/caption]
Erica Spatz, MD, MHS
Assistant Professor, Section of Cardiovascular Medicine
Center for Outcomes Research and Evaluation
Yale University School of Medicine/Yale-New Haven Hospital
New Haven, CT 06520
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Spatz: Rates of heart attack have declined during the last 15 years. But whether communities of different economic status or in different geographic regions experienced similar declines is unknown, especially as efforts to prevent cardiovascular disease and manage heart attacks may not have been equally successful in communities with different resource capacity.
Our study shows that trends in the incidence of and mortality from heart attack were similar in low, average and high income communities. However, low-income communities had higher hospitalization rates than average and high income communities throughout the 15 year study period. Interestingly mortality rates were similar.
Dr. Anny Xiang[/caption]
Anny H. Xiang, PhD
Kaiser Permanente Southern California Department of Research & Evaluation
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Xiang: Previous studies have identified a link between maternal obesity, diabetes and/or excessive gestational weight gain and long-term obesity risk in children. Our study examined the interplay among all four factors associated with childhood obesity: pre-pregnancy obesity, gestational weight gain, gestational diabetes and breastfeeding. To our knowledge, the interplay among these factors and their independent contributions to childhood obesity with data from a large and multi-ethnic cohort under current standard clinical care had not been previously studied.
The study included 15,710 women who delivered babies at Kaiser Permanente medical facilities in Southern California in 2011. The key findings were: