Dr. Cuilin Zhang[/caption]
Cuilin Zhang MD, PhD
Senior Investigator, Epidemiology Branch
Division of Intramural Population Health Research
NICHD/National Institutes of Health
Rockville, MD 20852
MedicalResearch.com: What is the background for this study?
Dr. Zhang: Hypertension is one of the most prevalent and preventable risk factors for cardiovascular and kidney diseases, and is one of the leading causes of death in the United States.
We have previously reported that the cumulative incidence of hypertension for women with a history of gestational diabetes mellitus (GDM) was 26% higher than those who did not have GDM even 16 years after the index pregnancy. Thus, women with a history of GDM represent a high-risk population for hypertension that could benefit from early prevention. While there is extensive literature on how lifestyle factors may influence blood pressure in the general population, no information is currently available on the role of diet and lifestyle in the development of hypertension specifically in this susceptible population. To address these gaps, we prospectively examined the associations between long-term adherence to three healthy diets with subsequent risk of hypertension among women with a history of gestational diabetes mellitus, specifically the DASH diet, the alternative Mediterranean diet (aMED), and the Alternative Healthy Eating Index (AHEI).
Dr. Yokoyama[/caption]
Jennifer S. Yokoyama, PhD
Assistant Professor, Memory and Aging Center
University of California, San Francisco
MedicalResearch.com: What is the background for this study?
Dr. Yokoyama: Alzheimer’s disease is a common neurodegenerative disease that occurs in older adults. Clinically, Alzheimer’s disease is primarily associated with changes in cognition (e.g., declines in memory, language and visuospatial functioning). Pathologically, Alzheimer’s disease is associated with misfolded amyloid beta and tau proteins and can only be definitively diagnosed at autopsy. It has long been appreciated that there is a link between the immune system and Alzheimer’s disease, and there are multiple sources of evidence that suggest that immune activity may be increased in patients with Alzheimer’s. Although there is strong evidence for an association between immune activity and Alzheimer’s disease there has always been a chicken-egg problem because we don’t know whether the Alzheimer’s disease process triggers the immune response or whether altered immune function promotes the Alzheimer’s disease process.
Genetic information can offer important clues about the role of the immune system in Alzheimer’s disease. Each person has a unique genetic fingerprint, and different combinations of gene changes (“variants”) put individuals at higher or lower risk for different diseases. Genetic data enables us to test whether having a certain genetic variant puts people at greater risk for both Alzheimer’s disease and autoimmune diseases, immune system diseases in which the immune system is overactive (e.g., Crohn's disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, Celiac's disease, and psoriasis). Rather than only responding to foreign objects such as bacteria and viruses, in autoimmune diseases the immune system also responds to the body’s own material, which do not ordinarily create an immune response, thereby leading to symptoms associated with higher levels of inflammation and other long-term problems. A variant that increases risk for both Alzheimer’s disease and autoimmune diseases would suggest a common biological pathway.
MedicalResearch.com: What are the main findings?
Dr. Yokoyama: In our study we tested whether there are genetic variants that put people at increased risk for both Alzheimer's disease and autoimmune diseases. We found eight genetic variants that influence people’s risk for both Alzheimer's disease and autoimmune disease. Some of these variants were associated with lower risk of autoimmune disease and Alzheimer’s disease, but two variants were associated with greater risk for both.
Dr. Joao Incio[/caption]
Joao Incio MD
Research Fellow in Radiation Oncology
Harvard Medical School/MGH
Boston, MA
MedicalResearch.com: What is the background for this study?
Dr. Incio: With the current epidemic of obesity, the majority of pancreatic cancer patients are overweight or obese at diagnosis. Importantly, obesity worsens treatment outcomes in pancreatic cancer patients. Therefore, understanding the mechanisms that underlie the poorer prognosis of obese cancer patients is of paramount importance. Obesity causes inflammation and fibrosis in the normal pancreas due to the accumulation of dysfunctional hypertrophic adipocytes. Importantly, desmoplasia - a fibroinflammatory microenvironment - is a hallmark of pancreatic ductal adenocarcinoma (PDAC), and we have shown that activation of pancreatic stellate cells (PSCs) via angiotensin-II type 1 receptor (AT1) pathway is a major contribution to tumor desmoplasia. Whether obesity affects desmoplasia in PDACs, and interferes with delivery and response of chemotherapeutics, was the focus of our study.
Prof. Harvey[/caption]
Professor Nicholas C W Harvey, MA MB BChir PhD FRCP
Professor of Rheumatology and Clinical Epidemiology
Honorary Consultant Rheumatologist
MRC Lifecourse Epidemiology Unit
University of Southampton
Southampton General Hospital
Southampton UK
MedicalResearch.com: What is the background for this study? What are the main findings?
Prof. Harvey: It is well established that fracture risk is substantially increased by having had a previous fracture. A previous study suggested that fracture risk soon after a spine fracture might be greater than the risk later on, and if the risk varies with time, it would be sensible to identify the time at greatest risk, so intervention can be given.
The risk of a second osteoporotic fracture was greatest immediately after the first fracture and thereafter decreased with time though remained higher than the population risk throughout follow up. For example, 1 year after the first fracture the risk of a second fracture was three times higher than the population risk. After 10 years it was two times higher.
Dr. Mariann Ratcliffe[/caption]
Marianne J. Ratcliffe, PhD
Associate director of diagnostics
AstraZeneca
Alderley Park, UK
MedicalResearch.com: What is the background for this study?
Dr. Ratcliffe: PD-L1 status is informative when considering monotherapy treatment and of growing importance when we consider that treatment decision will, in the near future also include combination therapy, an area of focus for AstraZeneca. The Ventana SP263 test has been developed with AstraZeneca, to support selection of PD-L1 testing within the Durvalumab programme, with full analytical validation at a 25% cut point derived from clinical data indicating this cut point best identifies patients more likely to respond to Durvalumab. The Ventana SP263 assay is commercially available in the US and the EU as a Class I device. The Dako 22C3 test has been approved as companion diagnostic for Pembrolizumab, and the Dako 28-8 has been released as a complementary diagnostic as an aid to physicians considering treatment with Nivolumab. What we didn’t know before our study was whether the three assays identify the same patients, and particularly how to cross compare patients identified with the different cut points specified for the different assays. It was therefore an important question to be addressed through a very thorough scientific assessment.
MedicalResearch.com: What are the main findings?
Dr. Ratcliffe: Our data, generated in 500 commercial samples, demonstrates that three commercially available PD-L1 tests achieved overall percentage agreement of >90%. This was achieved at multiple assay cut-offs. These results indicate that it may be possible to extrapolate the results from one test to that of another test. Further work is required to confirm this finding.
Dr. Ezequiel Morsella[/caption]
Ezequiel Morsella, Ph.D.
Associate Professor of Neuroscience
Department of Psychology
San Francisco State University
Assistant Adjunct Professor
Department of Neurology
University of California, San Francisco
Boardmember, Scientific Advisory Board
Institute of Cognitive Neurology (INECO),
Buenos Aires
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Morsella: The study is based on Passive Frame Theory, which I discuss below in brief, and on ironic processing, in which one is more likely to think about something (e.g., white bears) when instructed to not think about that thing. Based on this research, the Reflexive Imagery Task (RIT) reveals that, following the activation of certain "action sets" (i.e., dispositions to act one way or another), conscious thoughts can arise involuntarily and systematically when one is presented with certain stimuli. In the most basic version of the RIT, subjects are presented with visual objects and instructed to not think of the names of the objects, which is challenging. In the new study, we show that the effect arises not only for automatic processes (e.g., forms of cued-memory retrieval) but also for processes involving more, in a sense, moving parts (e.g., symbol manipulation, in which symbols are mentally manipulated). In the study, subjects were first trained to perform a word-manipulation task similar to the game of Pig Latin (e.g., “CAR” becomes “AR-CAY”). This task involves complex symbol manipulations. After training, though participants were instructed to no longer transform stimulus words in this way, the RIT effect still arose on roughly 40% of the trials.
The present experiment provides additional evidence for Passive Frame Theory, a new, comprehensive and internally coherent framework that illuminates the role of conscious processing in the brain. Click here for more information about Passive Frame Theory: https://www.psychologytoday.com/blog/consciousness-and-the-brain/201604/passive-frame-theory-new-synthesis
Although consciousness is not "epiphenomenal" (meaning that it serves no function) or omnipresent (e.g., as in panpsychism, which states that consciousness is a property of all matter), in Passive Frame Theory, the role of consciousness is much more passive and less teleological (i.e., less purposeful) than that of other theoretical accounts. The framework reveals that consciousness has few moving parts and no memory, no reasoning, or symbol manipulation, which is relevant to the present study. Consciousness does the same thing, over and over, for various processes, making it seem that it does more than it does. Hence, consciousness, over time, seems to be more flexible than it actually is.
Dr. Phillip Popovich[/caption]
Phillip G. Popovich, Ph.D.
Professor, Neuroscience
Director, Center for Brain and Spinal Cord Repair
Ray W. Poppleton Research Designated Chair
Department of Neuroscience
Wexner Medical Center at The Ohio State University
Columbus, Ohio 43210
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Popovich: People that suffer a spinal cord injury (SCI) at a high spinal level (e.g., cervical SCI), are at increased risk for developing autonomic dysreflexia (AD), a potentially life-threatening condition of sudden onset high blood pressure.
In people and animals with SCI, reflexes that are activated by routine stimuli including filling of the bladder or bowel often trigger AD.
We recently found that these same reflexes also suppresses the immune system (see Zhang et al., 2013; PMID 23926252)
Since people with high level spinal cord injury also are at increased risk for developing infections (e.g., pneumonia), we set out to understand how SCI changes the autonomic circuitry in the spinal cord that controls immune function.
We found that after a period of one month, the number of connections between spinal cord interneurons and autonomic neurons that directly control immune function increases dramatically.
Also, this newly formed circuitry is “hyperactive” and discharge of neurons in this circuit causes hormones to be released into the blood and immune organs that overstimulate immune cells, causing them to die.
Fortunately, we were able to show that the hyperactive spinal cord circuitry can be silenced. We used a novel technique known as “chemogenetics” to silence excitatory interneurons in the aberrant circuit. When the circuitry was silenced, immune cells were protected in spinal cord injury mice.
Dr. Thomas Sandora[/caption]
Thomas J. Sandora, M.D., M.P.H.
Senior Associate Physician in Medicine; Hospital Epidemiologist; Medical Director, Infection Control
Boston Children’s Hospital
Associate Professor of Pediatrics, Harvard Medical School
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Sandora: Giving antibiotics before certain types of operations results in lower rates of surgical site infections. However, there are limited data about which pediatric operations require antibiotic prophylaxis. We examined national variability in antibiotic prophylaxis for the 45 most commonly performed pediatric operations at children's hospitals in the U.S. We found that antibiotic use was considered appropriate for only 64.6% of cases, with a high degree of variability within procedures and between hospitals.
Dr. Laura McKenzie[/caption]
Dr. Lara B. McKenzie PhD MA
Principal Investigator
Center for Injury Research and Policy
The Research Institute
Nationwide Children’s Hospital
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. McKenzie: Skateboarding is a popular recreational sport and participation has increased the last several decades, faster than any other sport or recreation activity between 1998 and 2007 (National Sporting Goods Association Sports Participation in 2007). With growing participation, has come an increasing rate of injuries from skateboarding.
The study examined data for youth and adolescents 5-19 years of age who were treated in U.S. emergency departments (EDs) for skateboarding-related injuries from 1990-2008. It found that nationally, over the 19-year period, there was an average of 64,572 children and adolescents treated each year for skateboarding-related injuries – about 176 a day.
Most patients were male (89 percent), and were injured either at home (38 percent) or in the street and/or highway (30 percent). The most commonly injured body regions were the upper (45 percent) and lower (32 percent) extremities. The most common diagnoses were fractures or dislocations (33 percent), sprains and strains (25 percent) and bruises (20 percent). Children and adolescents 11-14 years of age were hospitalized more often than younger or older children/adolescents. Lower extremity injuries increased with age, while face and head or neck injuries decreased with age.
Dr. Adam Jacobson[/caption]
Adam S. Jacobson, MD
Associate Professor, Department of Otolaryngology-Head and Neck Surgery
Associate Director, Head and Neck Surgery
NYU Langone Medical Center and
Perlmutter Cancer Center
MedicalResearch.com Editor’s note: Dr. Jacobson is an Otolaryngologist, an Ear-Nose-Throat (ENT) physician specializing in the diagnosis of head and neck tumors and cancers, including cancers of the mouth and throat. Dr. Jacobson discussed oral (mouth) and pharyngeal (throat) cancers in recognition of Oral, Head and Neck Cancer Awareness Week.
MedicalResearch.com: How prevalent is the problem of Oral, Head and Neck Cancer? Is this type of cancer becoming more frequent?
Dr. Jacobson: Oropharynx cancer is currently on the rise.
MedicalResearch.com: Have HPV-induced cancers become more common?
(Note HPV or Human Papilloma Virus is a virus associated with various wart infections.)
Dr. Jacobson: Yes - Specifically tonsil and base of tongue cancer.
MedicalResearch.com Interview with Usman Khalid MD. Ph.D. fellow Department of Cardiology, Gentofte Hospital, Denmark MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Khalid: Psoriasis is a chronic inflammatory disease associated with increased risk of cardiovascular disease. Due to an overlap of key inflammatory mechanisms and risk factors, it is...
Dr. Samaan[/caption]
Dr. Zainab Samaan, MBChB, MSc, DMMD, PhD, MRCPsych
Associate Professor
Dept of Psychiatry and Behavioural Neurosciences
Member Population Genomics Program
Member Peter Boris Centre for Addiction Research
Associate Faculty Dept of Clinical Epidemiology and Biostatistics
McMaster University
Hamilton, ON, Canada
Medical Research: What is the background for this study?
Response: Opioid addiction has become a leading public health concern in North America with Canada leading the way in the amount of opioid use per capita. Opioid addiction has moved from heroin use by young men to prescription pain killers such as oxycodone and fentanyl with devastating impact on individuals and society including increasing number of deaths due to opioid overdose. In addition many people on treatment will also relapse (go back using drugs). We wanted to understand the problem of opioid addiction by investigating the factors that increase the risk of relapse in people with opioid addiction receiving methadone treatment.
Medical Research: What are the main findings?
Response: People who injected drugs and used benzodiazepines (BDZ) are more likely to relapse faster than people who did not use injection or benzodiazepines.
Dr. Van Morris[/caption]
Dr. Van K. Morris, MD
Assistant Professor, GI Medical Oncology
The University of Texas MD Anderson Cancer Center
MedicalResearch.com: What is the background for this study?
Dr. Morris: Anal cancer is a very rare cancer and accounts for approximately 2% of all gastrointestinal malignancies. Currently, there is no accepted standard of care for patients with metastatic disease, which raises challenges for oncologist who may not have extensive experience caring for patients with metastatic anal cancer given that there are not accepted agents to treat with. This clinical trial was the first clinical trial ever conducted for patients with stage IV disease who had received prior chemotherapy in the past.
Given the well-known association with human papilloma virus (HPV) and the development of anal cancer, we were interested in the use of immunotherapy drugs as a new possible way to awaken the immune system to attack this tumor, especially as there may be viral components in the tumor cells which the immune system could potentially recognize. Nivolumab is an immunotherapy drug which has shown activity in other solid tumors like melanoma, kidney cancer, non-small cell lung cancer, and bladder cancer.
Dr. Jacquelyn Kulinski[/caption]
Jacquelyn Kulinski, MD
Assistant Professor
Division of Cardiovascular Medicine
Medical College of Wisconsin
Milwaukee, WI 53226
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Kulinski: Sedentary behavior, or “sitting disease”, is increasingly recognized as a risk factor for cardiovascular disease, diabetes, cancer and early death. Many of these associations appear to be independent of exercise activity. The mechanisms through which sedentary behavior influences cardiovascular risk are largely unknown. Therefore, we investigated the association between accelerometer measured sedentary behavior and coronary artery calcium (CAC), a marker of subclinical heart disease, in over 2,000 participants using data from the Dallas Heart Study (DHS) population.
We found a significant association between increasing sitting time and CAC in a population without prior history of cardiovascular disease. This association was independent of measured exercise activity, traditional risk factors, and even socioeconomic factors. Each hour of sedentary time was associated with a 16% increase in CAC burden. Interestingly, the association between exercise and CAC was not significant in the fully-adjusted model.
Dr. Robotham[/caption]
Dr. Delphine Robotham MD
Division of Pediatric Nephrology
Johns Hopkins University School of Medicine
Baltimore, Maryland
Medical Research: What is the background for this study? What are the main findings?
Response: Cervical cancer is the second most common cancer in women worldwide and is almost entirely caused by high risk HPV genotypes. Vaccines to high risk HPV genotypes have shown great success in protecting healthy women from the sequelae of infection, including cervical cancer and genital warts. Young women with a kidney transplant as well as those with chronic kidney disease have abnormal immune systems and as a result have a significantly increased burden of HPV-related disease making the potential health benefits of the HPV vaccine substantial in this particularly vulnerable population. This study examined the immune response to the HPV vaccine among girls and young women with kidney disease.
The goal of this research was to determine if girls and young women with chronic kidney disease (abnormal kidney function, on dialysis, or post kidney transplant) showed evidence of immune response to the quadrivalent HPV vaccine. Immune response was determined by measuring the amount of antibody made by the patients against each of the 4 HPV genotypes included in the vaccine. There are established thresholds of antibody above which patients are believed to have protection from infection. We found that study participants with chronic kidney disease and those on dialysis had antibody levels above the threshold, indicating the vaccine should be effective in protecting them from HPV related disease. A significant proportion of patients with kidney transplants showed evidence of inadequate antibody response. This is important information as it means patients with a kidney transplant, whom we know are at increased risk of developing cervical cancer from HPV infection, may not be protected from HPV infections from the HPV genotypes included in the vaccine.
Dr. Thomas King[/caption]
Thomas C King, MD, PhD
Department of Pathology and Laboratory Medicine
Chief of Pathology and Laboratory Medicine
St. Vincent Hospital
Worcester, MA
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. King: This landmark study provides a broad based, real world appraisal of the reliability of the T-SPOT®.TB test, an interferon gamma release assay (IGRA), based on results in screening workers in 19 U.S. hospitals. The large size of the study (more than 42,000 test results from more than 16,000 healthcare workers analyzed) provides a solid benchmark to assess performance of T-SPOT.TB in serial screening healthcare workers. In recent years, results from several studies have shown that there can be significant differences between using an IGRA and the tuberculin skin test (TST) in terms of accuracy and cost. Several studies have confirmed a risk of high false positive rates and numerous conversion/reversion rates when retesting patients with the TST.
Dr. Barclay[/caption]
Dr. Kieron Barclay PhD
Department of Social Policy
London School of Economics
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Barclay: Mean age at childbearing has been increasing in most countries in the OECD since the early 1970s. A wealth of research has shown that childbearing at advanced ages is associated with greater difficulty in terms of getting pregnant, higher rates of miscarriage, stillbirth, and increased risk of poor peri-natal outcomes such as pre-term birth and low birth weight. Studies also indicate that the offspring of older mothers have a greater risk of Alzheimer’s disease, diabetes, and mortality in adulthood. However, from the perspective of any individual woman, delaying childbearing to an older age necessarily also means that she will give birth in a later birth year. The last 40 to 50 years have seen substantial improvements in educational opportunities, and better public health conditions and medical knowledge. As a result, these positive secular trends may outweigh or counterbalance the negative effects of reproductive aging for the child.
Dr. Harrys Torres[/caption]
Harrys A. Torres, MD, FACP, FIDSA
Associate Professor
Director of Hepatitis C Clinic
Department of Infectious Diseases, Infection Control and Employee Health
The University of Texas MD Anderson Cancer Center
Houston TX 77030
Medical Research: What is the background for this study? What are the main findings?
Dr. Torres: Hepatitis C virus (HCV) is an oncogenic virus and is associated with an increased risk of liver cancer and certain types of non-Hodgkin lymphomas. In 2009, at MD Anderson Cancer Center, we set up the first clinic in the United States, and probably in the world, specifically devoted to managing HCV infection in cancer patients. In the clinic, we expected to see a number of patients with liver cancers and non-Hodgkin’s lymphoma, as these have documented associations with HCV. Unexpectedly, we saw a high number of HCV-infected patients with head and neck cancers, and wondered whether there was an undiscovered association between having the infection and head and neck cancers. To explore this, we conducted a case-control study using 409 head and neck cancer subjects (164 oropharyngeal, 245 non-oropharyngeal [oral cavity, nasopharynx, larynx] cancers) and 694 control subjects with other smoking-associated cancers (378 lung, 168 esophagus, and 148 urinary bladder cancers), and compared the prevalence of HCV infection in the two groups. We observed a high prevalence of HCV infection in oropharyngeal (14%) and non-oropharyngeal (20%) cancer patients when compared to control subjects (6.5%). After adjusting for confounders such as smoking, alcohol intake, and socioeconomic status, HCV-infected individuals were 2.04 times more likely to have oropharyngeal cancers and 2.85 times more likely to have non-oropharyngeal cancers. Of note, HCV was associated only with patients with oropharyngeal cancers that tested positive for human papilloma virus, which is one of the main virus linked with increased risk of oropharyngeal cancers.
Dr. Robert Schiestl[/caption]
Robert H. Schiestl PhD
Department of Environmental Health Sciences, Fielding School of Public Health,
Department of Pathology
Department of Radiation Oncology
Geffen School of Medicine
University of California Los Angeles,
Los Angeles, California
Medical Research: What is the background for this study? What are the main findings?
Dr. Schiestl: When we moved from Harvard to UCLA 13 years ago, after 6 years at UCLA our Atm mouse colony lived significantly 4 fold longer and the frequency of DNA deletions was 4.5 fold reduced and the latency of lymphoma 2.5 fold different. Ultimately we identified the reason behind this as a difference in the intestinal bacteria. The Atm deficient mice are hypersensitive to inflammation and the bacteria reduced inflammation. Then I isolated the most prevalent bacterium among the health beneficial bacteria and this bacterium by itself called Lactobacillus johnsonii 456 reduced genotoxicity and all markers of inflammation.
Dr. Charles Pollack[/caption]
Dr. Charles Pollack MD MA
Thomas Jefferson University
Philadelphia, PA 19107
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Pollack:: We are continuing research on PRAXBIND in the ongoing global phase III patient study, RE-VERSE AD™. RE-VERSE AD includes two groups of dabigatran patients: those who had serious bleeding or those who required an urgent procedure.
At ACC, we presented results from an updated interim analysis from 123 patients enrolled in RE-VERSE AD™, which showed a single 5g of PRAXBIND immediately reversed the anticoagulant effect of dabigatran in all patients evaluated.