Author Interviews, Brigham & Women's - Harvard, JAMA, Nutrition, Ophthalmology / 16.01.2016
Dietary Nitrates From Green Leafy Vegetables Linked To Decreased Glaucoma Risk
More on Ophthalmology on MedicalResearch.com
MedicalResearch.com Interview with:
Jae Hee Kang, MSc, SC
Associate Epidemiologist, Brigham and Women's Hospital
Assistant Professor of Medicine, Harvard Medical School
Brigham and Women's Hospital
Department of Medicine
Channing Division of Network Medicine
Boston, MA 02115
Medical Research: What is the background for this study? What are the main findings?
Dr. Kang: Glaucoma is a leading cause of irreversible blindness worldwide, and primary open-angle glaucoma (POAG) is the most common form of the disease. Little is known on the causes of glaucoma but dysfunction in the regulation of blood flow to the optic nerve, which transmits visual information to the brain, may be involved. Nitric oxide is important for maintenance of blood flow and its signaling may be impaired in glaucoma. We were interested in whether dietary nitrates, an exogenous source of nitric oxide mostly found in green-leafy vegetables, may be related to lower risk of POAG.
Medical Research: What is the background for this study? What are the main findings?
Dr. Kang: We (Brigham and Women’s Hospital / Harvard Medical School and Massachusetts Eye and Ear researchers) used 25+ years of data from over 100,000 participants in the Nurses' Health Study (63,893 women) and the Health Professionals Follow-up Study (41,094 men). Participants were nurses or other health professionals and were aged 40 years or older and reported eye exams. We collected information on their diet and other health information every two years with questionnaires. During follow-up, 1,483 new cases of primary open-angle glaucoma with visual field loss were identified and confirmed with medical record review. Participants were divided into quintiles (one of five groups) of dietary nitrate intake (quintile 5, approximately 240 mg/day; quintile 1, approximately 80 mg/day) and of green leafy vegetables (quintile 5, approximately 1.5 servings/day; quintile 1, approximately one-third of a serving/day). We observed that greater intake of dietary nitrate and green leafy vegetables (e.g., romaine and iceberg lettuce and kale/chard/mustard greens) was associated with a 20 percent to 30 percent lower POAG risk; the association was particularly strong (40 percent-50 percent lower risk) for POAG with early paracentral visual field loss (a subtype of POAG most linked to dysfunction in blood flow autoregulation).
Dr. Dai Fukumura[/caption]
MedicalResearch.com Interview with:
Dai Fukumura, M.D., Ph.D.
Joao Incio, M.D.
and Rakesh K. Jain, Ph.D
Edwin L. Steele Laboratory
Department of Radiation Oncology
Massachusetts General Hospital
Harvard Medical School
Medical Research: What is the background for this study? What are the main findings?
Dr. Fukumura: This study focused on pancreatic ductal adenocarcinoma, the most common form of pancreatic cancer, which accounts for almost 40,000 cancer death in the U.S. ever year. Half of those diagnosed with this form of pancreatic cancer are overweight or obese, and up to 80 percent have type 2 diabetes or are insulin resistant. Diabetic patients taking metformin – a commonly used generic medication for type 2 diabetes – are known to have a reduced risk of developing pancreatic cancer; and among patients who develop the tumor, those taking the drug may have a reduced risk of death. But prior to the current study the mechanism of metformin’s action against pancreatic cancer was unclear, and no potential biomarkers of response to metformin had been reported.
We have uncovered a novel mechanism behind the ability of the diabetes drug metformin to inhibit the progression of pancreatic cancer. Metformin decreases the inflammation and fibrosis characteristic of the most common form of pancreatic cancer. We found that metformin alleviates desmoplasia – an accumulation of dense connective tissue and tumor-associated immune cells that is a hallmark of pancreatic cancer – by inhibiting the activation of the pancreatic stellate cells that produce the extracellular matrix and by reprogramming immune cells to reduce inflammation. Our findings in cellular and animal models and in patient tumor samples also indicate that this beneficial effect may be most prevalent in overweight and obese patients, who appear to have tumors with increased fibrosis.
Dr. NaNa Keum[/caption]
Dr. Fox[/caption]
MedicalResearch.com Interview with:
Dr. Caroline Fox, MD MPH
National Heart, Lung, and Blood Institute
Assistant Clinical Professor of Medicine
Harvard Medical School
Medical Research: What is the background for this study? What are the main findings?
Dr. Fox: There is evidence linking sugar sweetened beverages with obesity and type 2 diabetes. There is also evidence suggesting that specific adipose tissue depots may play a role in the pathogenesis of these diseases. We found that higher levels of
Dr. Charlton[/caption]
MedicalResearch.com Interview with:
Brittany M. Charlton, ScD
Instructor
Boston Children's Hospital and Harvard Medical School
Researcher, Harvard Chan School Department of Epidemiology
Boston, MA 02115
Medical Research: What is the background for this study? What are the main findings?
Dr. Charlton: Even though oral contraceptives can be over 99% effective with perfect use, almost 10% of women become pregnant within their first year of use. Many more women will stop using oral contraceptives when planning a pregnancy and conceive within just a few months. In both of those examples, a woman may inadvertently expose her offspring during pregnancy to exogenous sex hormones. We conducted a nationwide cohort study in Denmark in order to investigate whether oral contraceptive use shortly before or during pregnancy was associated with an increased risk of major birth defects in the offspring. Our main finding was that there was no increased risk of having a birth defect associated with oral contraceptive exposure. These results were also consistent when we broke down the birth defects into different subgroups, like limb defects.
Dr. Little[/caption]
MedicalResearch.com Interview with:
Dr. Sarah Elizabeth Little, MD
Obstetrics/Gynecology
Department of Obstetrics and Gynecology
Brigham and Women's Hospital
Medical Research: What is the background for this study? What are the main findings?
Dr. Little: This study investigates the variation in cesarean delivery rates across hospital services areas (a geographic unit designed by the Dartmouth Atlas to represent local markets for primarily hospital-based medical services). We looked at whether variation in cesarean delivery rates was related to broader variation in overall medical spending and utilization in that area, which we measured with Medicare spending and hospital use at the end-of-life. We found that an area’s cesarean delivery rate was correlated with these other measures; in other words, the hospital services areas that are doing the most cesarean deliveries are the same ones that are spending more and doing more to non-obstetric patients as well.
Dr. Trinh[/caption]
MedicalResearch.com Interview with:
Quoc-Dien Trinh MD
Assistant Professor, Harvard Medical School
Brigham and Williams Hospital
Medical Research: What is the background for this study? What are the main findings?
Dr. Trinh: Among elderly Medicare beneficiaries with metastatic prostate cancer, surgical castration is associated with lower risks of any fractures, peripheral arterial disease, and cardiac-related complications compared to medical castration using GnRH agonists.
Dr. Odejide[/caption]
MedicalResearch.com Interview with:
Oreofe O. Odejide, MD
Instructor in Medicine, Harvard Medical School
Dana-Farber Cancer Institute
Medical Research: What is the background for this study? What are the main findings?
Dr. Odejide: The care that patients with hematologic cancers receive near the end of life is distinct from patients with solid tumors. For instance, previous research has shown that patients with blood cancers are more likely to receive intensive care at the end of life such as chemotherapy within 14 days of death, intensive care unit admission within 30 days of death, and they are less likely to enroll in hospice. My colleagues and I hypothesized that timing of discussions regarding end-of-life preferences with patients may contribute to these findings, and we wanted to examine hematologic oncologists’ perspectives regarding end-of-life discussions with this patient population.
We conducted a survey of a national sample of hematologic oncologists obtained from the publicly available clinical directory of the American Society of Hematology. We received responses from 349 hematologic oncologists, giving us a response rate of 57.3%. In our survey, we asked hematologic oncologists about the typical timing of EOL discussions in general, and also about the timing of the first discussion regarding resuscitation status, hospice care, and preferred site of death for patients. Three main findings emerged:
Dr. Qi Sun[/caption]
MedicalResearch.com Interview with:
Dr. Qi Sun Sc.D
Assistant Professor
Department of Nutrition
Harvard T.H. Chan School of Public Health
Boston, Massachusetts
Medical Research: What is the background for this study? What are the main findings?
Dr. Qi Sun: Potato is considered as a vegetable in certain dietary recommendations, such as in the U.S. MyPlate food guide, whereas in the U.K. national food guide, potato is grouped with cereal as sources of carbohydrates. Potato foods are typically higher in glycemic index and glycemic load, but data are rare regarding whether individual and total potato foods are associated with chronic diseases. In this analysis, we focused on diabetes and found that a higher consumption of total potato foods and individual potato foods, especially french fries, was associated with an increased risk of developing type 2 diabetes in three large cohort studies of ~200 thousand U.S. men and women. In addition, we found that increased potato food consumption over time was associated with a subsequent increased risk of developing diabetes.
Dr. Erik Alexander[/caption]
MedicalResearch.com Interview with:
Dr. Erik K. Alexander, MD FACP
Chief, Thyroid Section, Division of Endocrinology
Brigham & Women's Hospital
Associate Professor of Medicine, Harvard Medical School
Medical Research: What is the background for this study? What are the main findings?
Dr. Alexander: Thyroid nodular disease has become an increasingly common medical illness, with prevalence reported to range between 26-67% in the adult. Though advancing age is known to influence the formation of thyroid nodules, their precise relationship remains unclear. Furthermore, it is uncertain whether age influences the risk that any thyroid nodule may prove cancerous. Thus we conducted a study to determine the impact of patient age on nodule formation, the number of
Dr. Walter Dzik[/caption]
MedicalResearch.com Interview with:
Dr. Walter H. Dzik MD
Associate Pathologist, Massachusetts General Hospital
Associate Professor of Pathology
Harvard Medical School
Medical Research: What is the background for this study? What are the main findings?
Dr. Dzik: Millions of Red Blood Cell transfusions are given each year. To maintain adequate blood inventories worldwide, Red Blood Cell units are stored under refrigerated conditions. Previous animal and laboratory research has highlighted the fact that red cells undergo biochemical, morphologic, and biophysical changes during prolonged refrigerated blood storage. Researchers and clnicians have questioned whether the changes that occur during storage would impair the ability of transfused Red Cells to delivery oxygen to tissues.
Our study was a randomized controlled trial conducted in patients with extreme anemia and insufficient global tissue oxygenation. We randomly assigned children with severe anemia and lactic acidosis to receive Red Blood Cells stored 1-10 days versus Red Blood Cells stored 25-35 days. We measured the recovery from lactic acidosis in response to transfusion in the two groups. We also measured cerebral tissue oxygenation using a non-invasive tissue oximeter. We found that the proportion of patients who achieved reversal of lactic acidosis was the same in the two RBC storage-duration groups. The rate of decline of lactic acidosis was also equal. There was also no difference in cerebral oxygenation, resolution of acidosis, correction of vital signs, clinical recovery, survival and 30-day followup.
Dr. Jamie Stagl[/caption]
MedicalResearch.com Interview with:
Dr. Jamie Stagl, PhD
Was a Ph.D. student in Psychology at University of Miami during the research period
Currently, a post-doctoral fellow in Psychiatric Oncology
Massachusetts General Hospital Cancer Center in Boston
Medical Research: What is the background for this study? What are the main findings?
Dr. Stagl: This is a newly published finding from a randomized trial funded by the National Cancer Institute that showed that women with breast cancer who received stress management skills early on in their treatment had longer survival and longer time without breast cancer recurrence at eight to 15 years after their initial diagnosis. This secondary analysis is published online and in the November 2015 issue of Breast Cancer Research and Treatment.
The study was conducted by senior investigator, Michael Antoni, Ph.D., Survivorship Theme Leader of the Cancer Control research program at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine and Professor of Psychology and Psychiatry and Behavioral Sciences, and his research team, including lead author Jamie Stagl, Ph.D., currently a postdoctoral fellow at Massachusetts General Hospital Cancer Center in Psychiatric Oncology and Behavioral Sciences.
In this trial, women received an intervention called Cognitive-Behavioral Stress Management, which was created by Dr. Michael Antoni at the University of Miami. After surgery for breast cancer, women received 10 weekly, group-based sessions of skills to manage stress based in
Dr. Boiselle[/caption]
MedicalResearch.com Interview with:
Phillip Boiselle, M.D.
Staff, Cardiothoracic Imaging
Beth Israel Deaconess Medical Center
Associate Dean for Academic and Clinical Affairs
Professor of Radiology, Harvard Medical School
Boston, Mass
Medical Research: What is the background for this study? What are the main findings?
Dr. Boiselle: Previous studies have shown that women have a greater mortality benefit from lung cancer screening then men, and that this test (CT screening) is more cost-effective for women than men. Our purpose was to determine whether the relative risk of lung cancer for women and men differed depending on the specific type of lung nodule that was discovered at screening. Such differences could potentially help to influence a more personalized approach to patient management in lung cancer screening.
Dr. Jason Gold[/caption]
MedicalResearch.com Interview with:
Jason S. Gold MD FACS
Chief of Surgical Oncology, VA Boston Healthcare System
Assistant Professor of Surgery, Harvard Medical School
Brigham and Women’s Hospital
Medical Research: What is the background for this study?
Dr. Gold: Pancreas cancer is a lethal disease. While advances in the best available care for pancreas cancer are desperately needed, improvements can be made in addressing disparities in care. This study aimed to evaluate associations of social and demographic variables with the utilization of surgical resection as well as with survival after surgical resection for early-stage pancreas cancer.
Medical Research: What are the main findings?
Dr. Gold: The main findings are the following:
1: We found that less than half of patients with early-stage pancreas cancer undergo resection in the United States. Interestingly, the rate of resection has not changed with time during the eight-year study period.
2. We also found significant disparities associated with the utilization of surgical resection for early-stage pancreas cancer in the United States. African American patients, Hispanic patients, single patients, and uninsured patients were significantly less likely to have their tumors removed. There were regional variations in the utilization of surgical resection as well. Patients in the Southeast were significantly less likely to have a pancreas resection for cancer compared to patients in the Northeast.
3. Among the patients who underwent surgical resection for early-stage pancreas cancer, we did not see significant independent associations with survival for most of the social and demographic variables analyzed. Surprisingly, however, patients from the Southeast had worse long-term survival after pancreas cancer resection compared to those in other regions of the United States even after adjusting for other variables.
Dr. Lubitz[/caption]
MedicalResearch.com Interview with:
Carrie C. Lubitz, MD, MPH
Assistant Professor of Surgery, Harvard Medical School
Senior Scientist, Institute for Technology Assessment
Attending Surgeon, Mass General/North Shore Center for Outpatient Care
Danvers, Massachusetts
Medical Research: What is the background for this study? What are the main findings?
Dr. Lubitz: Given reported estimates of resistant hypertension and the proportion of resistant hypertensive patients with primary hyperaldosteronism (PA) - the most common form of secondary hypertension caused by a nodule or hyperplasia of the adrenal glands – we estimate over a million Americans have undiagnosed PA. Furthermore, it has been shown that patients with PA with the same blood pressure as comparable patients with primary hypertension have worse outcomes.
In our study, we found that identifying and appropriately treating patients with PA can improve long-term outcomes in patients in a large number of patients who have resistant hypertension.
Dr. Vonberg[/caption]
MedicalResearch.com Interview with:
Frederick W. Vonberg, MA, MBBS
Research Fellow in Neurocritical Care
Boston Children's Hospital and Harvard Medical School
Medical Research: What is the background for this study? What are the main findings?
Response: An association between schizophrenia and epilepsy has long been suspected, ever since people noticed similarities in some aspects of the presentation of the two conditions, and in their epidemiology. For example, people with epilepsy are thought to be more at risk of developing schizophrenia. Furthermore, a psychosis resembling schizophrenia can characterize some forms of
Dr. Lei Xu[/caption]
MedicalResearch.com Interview with:
Lei Xu, MD, PhD
Steele Laboratory of Tumor Biology
Radiation Oncology Department
Massachusetts General Hospital
Medical Research: What is the background for this study?
Dr. Lei Xu: Neurofibromatosis 2 is characterized by benign tumors that develop throughout the nervous system. The most common site of these tumors is the eighth cranial nerve, which carries hearing and balance information from the ears to the brain. Although these vestibular schwannomas grow slowly, they usually lead to a significant or total hearing loss by young adulthood or middle age. The tumors can also press on the brain stem, leading to headaches, difficulty swallowing and other serious neurologic symptoms. While the tumors can be surgically removed or destroyed with radiation treatment, both approaches can also damage hearing.
Several previous investigations had suggested that – unlike other benign tumors – vestibular schwannomas induce the formation of new blood vessels, as malignant tumors do. A 2009 New England Journal of Medicine study led by Scott Plotkin, MD, PhD, at Massachusetts General Hospital reported that treatment with the antiangiogenesis drug bevacizumab caused shrinkage of NF2-schwannomas in most of the treated patients and improved hearing in more than half. But the limitations of that approach – the fact that not all patients responded, that the hearing improvement was often transient and that some patients could not tolerate long-term bevacizumab treatment – indicated the need to better understand the mechanisms of anti-angiogenesis on the function of tumor-bearing nerves.
MedicalResearch.com Interview with:
Dr. Priscilla Kaliopi Brastianos MD
Instructor, Medicine, Harvard Medical School
Assistant Physician in Medicine
Hematology/Oncology, Massachusetts General Hospital
Medical Research: What is the background for this study? What are the main findings?
Response: Craniopharyngiomas are rare brain tumors that can cause serious problems because of their location near critical structures in the brain, such as optic and other cranial nerves, the pituitary gland and the hypothalamus. Not only does the growing tumor compromise neurological and hormonal functions by impinging on these structures, but treatment by surgical removal or radiation therapy can produce the same symptoms by damaging adjacent tissues. In addition, since the tumor adheres to these nearby critical structures, complete removal is difficult, which can lead rapid recurrence. Medical therapies have not been effective for craniopharyngiomas, namely because we did not understand the molecular underpinnings of these tumors. Last year, we performed genomic characterization of craniopharyngiomas, with the goal to identify potential therapeutic targets. We were surprised to find that nearly all papillary craniopharyngiomas have BRAF mutations, which are the same mutations that have been found in 






