medicalresearch.com: medical research exclusive interviews january 7 2014

MedicalResearch.com

MedicalResearch.comExclusive Interviews with Medical Research and Health Care Researchers from Major and Specialty Medical Research Journals and MeetingsEditor: Marie Benz, MD [email protected] 7 2015

For Informational Purposes Only: Not for Specific Medical Advice.

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Read more interviews on MedicalResearch.comHealthy Aging Brain Care Tool Allows Quick Assessment of Cognitive FunctionMedicalResearch.com Interview with:Patrick Monahan, Ph.D.Associate ProfessorIndiana University School of Medicine and School of Public Health

Medical Research: What is the background for this study?

Dr. Monahan: Primary care providers need a clinical practical (e.g., brief, inexpensive, simple, user-friendly, easily standardized, and widely available) multidomain instrument to measure and monitor the cognitive, functional, and psychological symptoms of patients suffering from multiple chronic conditions. The tool also needs to be sensitive to change so that providers can use it to monitor patient outcomes and adjust the care plan accordingly. We created such a tool and then investigated its psychometric properties (in other words, reliability and validity) in our study of 291 older patients (aged 65 and older) who had at least one recent visit to our urban primary care clinics in Indianapolis, Indiana. These patients had presented with evidence of cognitive or depression problems because these patients and their caregivers were participating in a collaborative care model for such patients.Medical Research: What are the main findings?Dr. Monahan: The Healthy Aging Brain Care (HABC) Monitor demonstrated excellent reliability and validity in this study where patients self-reported their symptoms. Our previous study also showed excellent reliability and validity of the HABC Monitor when the patients symptoms were reported by their informal caregiver.

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Healthy Aging Brain Care Tool Allows Quick Assessment of Cognitive FunctionMedicalResearch.com Interview with:Patrick Monahan, Ph.D.Associate ProfessorIndiana University School of Medicine and School of Public Health

Medical Research: What should clinicians and patients take away from your report?Dr. Monahan: The patient Self-Report HABC Monitor can be used along with the Caregiver-report version of the tool to provide useful feedback (via monitoring of symptoms) for modifying care plans.Medical Research: What recommendations do you have for future research as a result of this study?Dr. Monahan: We are in the process of developing a briefer 10-item version of the HABC Monitor which was requested by our clinical colleagues for the busy primary setting. As with the current tool, the briefer version is relevant for all primary care patients, but especially relevant for patients and their caregivers being treated with a collaborative care model for treating depression and cognitive impairment, given the importance of the cognitive, psychological, and functional domains. However, those domains are important for all patients in primary care who may suffer from a variety of chronic conditions. In addition, we are building on the HABC Monitor to develop a broader multidomain (but still relatively brief, for example, 20-item) tool that covers additional domains, such as actionable physical symptoms, to monitor the symptoms patients who attend primary care with a range of multiple chronic conditions such as cancer, diabetes, stroke, dementia, traumatic brain injury, heart failure, depressive disorders, anxiety disorders, and chronic musculoskeletal disorders.Citation:The Healthy Aging Brain Care (HABC) Monitor: Validation of the Patient Self-Report Version of the Clinical Tool Designed to Measure and Monitor Cognitive, Functional, and Psychological Health Clinical Interventions in AgingPatrick O Monahan,1 Catherine A Alder,24 Babar A Khan,13 Timothy Stump,1 Malaz A Boustani14December 2014 Volume 2014:9 Pages 21232132http://dx.doi.org/10.2147/CIA.S64140

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Stem Cells Can Be Grown From Blood Of Deceased PatientsMedicalResearch.com Interview with:Dr. Dhruv Sareen, PhDDirector, iPSC Core Facility Regenerative Medicine Institute Research Scientist, Neurobiology ResearchCedars-Sinai, Los Angeles CA

Medical Research: What is the background for this study? What are the main findings?

Dr. Sareen: We have developed a novel method to re-create brain and intestinal stem cells from patients who died decades ago, using stored blood samples. Using the iPS cell technology at Cedars-Sinai this new method now allows us to apply to alive as well as deceased patient blood cells. Our study, published in the journal STEM CELLS Translational Medicine, highlights the power of this technology for many deceased patients that were diagnosed with debilitating diseases, such as inflammatory bowel disease (IBD) and motor neuron diseases (spinal muscular atrophy and ALS). Patients had their blood samples stored away at Cedars-Sinai when they were alive decades ago. At that time all researchers could have done was collect and bank their blood cell lines for research purposes. The iPS cell technology wasnt even on scientists radar then. With novel developments in my lab we have figured out how to reliably create new stem cell lines from patient blood samples stored away in large cell banks. We have also shown that these recreated stem cells can efficiently make neurons specific to the spine (motor) and cells of the gut. Since it is very difficult to get unlimited access to research affected cells and tissues from the patients, our discoveries now allow us such important capabilities. Thus, now we are not limited to animal models of disease, but can use these patient-specific stem cells to better pinpoint potential causes of these devastating illnesses.Medical Research: What should clinicians and patients take away from your report?Dr. Sareen: This research, published in the journal STEM CELLS Translational Medicine, could yield new therapies for people who suffer from aggressive motor-neuron and gut-related IBD conditions that proved fatal to the deceased patients who long-ago volunteered their blood samples. Using patient iPS cells that we can recreate unlimited number of cell types that are much more relevant as they are the ones affected during disease. This provides researchers with better platform systems to screen for thousands of candidate drugs in the future.

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Stem Cells Can Be Grown From Blood Of Deceased PatientsMedicalResearch.com Interview with:Dr. Dhruv Sareen, PhDDirector, iPSC Core Facility Regenerative Medicine Institute Research Scientist, Neurobiology ResearchCedars-Sinai, Los Angeles CA

Medical Research: What recommendations do you have for future research as a result of this study?Dr. Sareen: The potential implications of this kind of research are vast. This significant development provides an easier modality for the creation of powerful patient-specific stem cells (iPS cells). Potentially, any patient at Cedars-Sinai can have their iPS cells created, thus allowing us to study a wider range of diseases. In the near term, this technology allows us to generate disease-relevant cell types (gut and brain) to guide us forward in identifying novel and yet unknown disease mechanisms in IBD and SMA. When the patients blood cells (LCLs) were stored years ago they were utilized in genetic studies to assess if specific alterations in their DNA code were responsible for their disease. By now obtaining their iPS cells, then creating affected gut and brain cell types we are correlating the clues these cells provide with the large wealth of knowledge gained previously from the genetic studies. This will ultimately allow us to design better drugs. Although we are unable to help the deceased patients, long term, these iPS cells will also allow us to create healthy versions of cell types that can regenerate the damaged tissue affected for patients currently suffering with such diseases. All of these future possibilities will allow us to design better therapies for patients suffering from SMA and IBD.Citation:Reliable Generation of Induced Pluripotent Stem Cells From Human Lymphoblastoid Cell LinesRobert Barrett, Loren Ornelas, Nicole Yeager, Berhan Mandefro, Anais Sahabian, Lindsay Lenaeus, Stephan R. Targan, Clive N. Svendsen, Dhruv SareenStem Cells Trans Med 2014; 3:1429-1434; first published on October 8, 2014; doi:10.5966/sctm.2014-0121

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Human Trafficking During Global Sporting Events Needs More StudyMedicalResearch.com Interview with:Dr. Rebecca Finkel PhD Queen Margaret University Edinburgh, Scotland, UK andMadelon Finkel, Ph.D. Director Professor of Clinical Public HealthWeill Cornell Medical College, NY, NY


Drs. Finkel: Human trafficking is as complex human rights and public health issue. One of the authors (RF) studied the issue at the Vancouver Olympic Games and felt that there needed to be more research on this topic. Much of the problem is that the issue of human trafficking for sexual exploitation at mega global sporting events is difficult to quantify given the clandestine nature of the industry. This is not to say that human trafficking for sexual exploitation does not occur. It almost certainly exists, but to what extent is the big question and to what extent do global events have an impact (if at all)? Our article shows that there are few well-designed empirical studies that address the issue of human trafficking, especially as it relates to mega sporting events.The extant literature presents gaps in:a) understanding the actual scope of the international human trafficking situation;b) establishing links between human trafficking and mega sporting events despite anecdotal testimonies and moral panics often fueled by international media; and,c) public health implications for victims of human trafficking.Medical Research: What should clinicians and patients take away from your report?Drs. Finkel: Findings show a high prevalence of physical and mental violence among those trafficked compared to non-trafficked women. Sexually transmitted infections and HIV AIDS are prevalent and preventive care is virtually non-existent. The Public Health implications are potentially substantial both for the victim and for her sexual partner.

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Human Trafficking During Global Sporting Events Needs More StudyMedicalResearch.com Interview with:Dr. Rebecca Finkel PhD Queen Margaret University Edinburgh, Scotland, UK andMadelon Finkel, Ph.D. Director Professor of Clinical Public HealthWeill Cornell Medical College, NY, NY

Medical Research: What recommendations do you have for future research as a result of this study?Drs. Finkel: Human trafficking for sexual exploitation is a hidden problem on a global scale in plain view with tremendous public health implications. From a research perspective, it is recommended that a research agenda in this important area be devised with consistent, robust methodologies and approaches in order to collect reliable data in the areas of human trafficking, public health, and their intersection during times of mega sporting events. Due to difficulties quantifying the scope of human trafficking, it is suggested that qualitative and mixed methods should be employed. Although research could and should involve authorities, it also would be helpful if it were to go beyond official channels to study people involved in human trafficking prevention, protection, prosecution and partnerships as well as survivors themselves in order more fully to comprehend a holistic view of the contemporary landscape of voluntary and involuntarily sex industries.Citation:The dirty downside of global sporting events: focus on human trafficking for sexual exploitationR. Finkel and M.L. FinkelPublic HealthAvailable online 29 December 2014

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Many At-Risk Adolescents Have Access To Firearms In HomeMedicalResearch.com Interview with:Joseph A Simonetti, MD MPH Research FellowHarborview Injury Prevention & Research CenterUniversity of Washington Seattle, WA, USA


Dr. Simonetti: Studies have consistently shown that children living in households where firearms are stored safely have a lower risk of suffering firearm injuries, including lethal firearm injuries, compared to those living in households where firearms are stored unlocked and/or loaded. Safe firearm storage is widely recommended by public health experts, professional medical societies, and gun rights organizations, especially for households where children might be suffering from mental heath and substance abuse issues that put them at increased risk for suicide or unintentional injury. Our goal was to find out if those recommendations were being effectively implemented in the community. To do this, we used survey data that assessed mental health conditions and firearm access among a nationally representative sample of US adolescents.Medical Research: What are the main findings?Dr. Simonetti: First, we confirmed previous findings that a large proportion of US adolescents have access to a firearm in the home. Of those who reported living in a home with a firearm, 40% said they could immediately access and shoot the firearm.Second, the prevalence of most mental health diagnoses was similar between adolescents who did and did not report firearm access. However, a greater proportion of adolescents with firearm access had drug and alcohol disorders compared to adolescents who reported living in a home with a firearm but did not have access to the firearm.The main finding was that children with mental health risk factors for suicide were just as likely to report in-home firearm access as those without identified risk factors. This finding held true even when comparing firearm access between children with no identified risk factors and those who reported a recent suicide attempt, who arguably have the highest suicide risk in this sample.


Medical Research: What should clinicians and patients take away from your report?Dr. Simonetti: For clinicians this study shows that a large proportion of US adolescents have access to firearms in the home, and those with mental health risk factors for suicide were just as likely to report in-home firearm access as those without identified risk factors. A number of studies have demonstrated effective ways to promote safe firearm storage in clinical settings. Importantly, several studies have shown that parents are not offended when providers ask about safe firearm storage during clinical encounters.For parents Safe firearm storage includes keeping firearms locked, unloaded, separate from locked ammunition, and ensuring that children dont know how to access those firearms. Studies have consistently shown that children living in homes with safely-stored firearms are less likely to be shot, and safe firearm storage is widely recommended by gun rights organizations and public health officials. Trigger locks and gun lockboxes can be purchased for less than $10 online, and in common stores such as Walmart and Costco.


Medical Research: What recommendations do you have for future research as a result of this study?Dr. Simonetti: There is an obvious disconnect between generally agreed upon recommendations for firearm safety practices and what were actually doing in the community. Additional studies are needed to determine how best to promote safe firearm storage in US households through clinical and community-based interventions, especially for households with children and children with mental illness.Studies of physicians have shown that not all clinicians are asking about guns in the home, or how those guns are stored. Future studies are needed to identify ways to address barriers to asking about firearm ownership and storage in clinical settings, especially for clinicians caring for children with increased risk of self-inflicted injuries.Citation:Simonetti JA, Mackelprang JL, Rowhani-Rahbar A, Zatzick D, Rivara FP. Psychiatric Comorbidity, Suicidality, and In-Home Firearm Access Among a Nationally Representative Sample of Adolescents. JAMA Psychiatry. Published online December 30, 2014. doi:10.1001/jamapsychiatry.2014.1760.

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Alternatives To Hysterectomy May Be UnderutilizedMedicalResearch.com Interview with:Lauren Corona BSWayne State University School of MedicineDetroit, MI


Response: Hysterectomy is the most commonly performed major gynecologic surgery in the United States. This study sought to examine how often alternative treatment is considered prior to hysterectomy for benign indications and how often pathology in the surgical specimen supports the need for hysterectomy. We utilized data from the Michigan Surgical Quality Collaborative, a statewide hospital collaborative, and limited the analysis to patients having a hysterectomy for uterine fibroids, abnormal uterine bleeding, endometriosis, and/or pelvic pain. Alternative treatment to hysterectomy was not documented prior to surgery in 38% (i.e. no documentation that the patient declined, was unable to tolerate, or failed any alternative treatment). A progesterone intrauterine device (IUD) was the least utilized form of alternative treatment, documented in only 12% of patients. In addition, nearly 1 in 5 (18.3%) had pathology reported that did not support the need for hysterectomyi.e. the uterus was described as normal or unremarkable or only had minor amounts of pathology. Women 65 years of age enrolled in Medicare who underwent surgical replacement of their aortic valve and survived at least one year, 3 in 5 were free from hospitalization during that year. Both, the rates of hospitalization and the average total number of days spent in the hospital in the year following surgery have been decreasing all through the last decade (1999 to 2010).Medical Research: What should clinicians and patients take away from your report?Response: Surgical valve replacement is becoming safer over time. Our previous study showed that over the last decade 1-year survival after aortic valve replacement increased from 86% to 89%. Our present study shows that the majority of these survivors are free from hospitalization and the need to be hospitalized is continually decreasing (from 44% to 41%).These days, newer techniques of valve replacement not requiring open surgery have emerged. Some studies show them to be comparable in mortality outcomes. However, there is no comparable data for the need for hospitalization, which is equally important to patients. Further, our previous study showing declining mortality and the present one showing the decreasing need for hospitalization indicate that these newer procedures are pitted against a continually improving target.There are certain sub-groups of patients like patients older than 85, female or black patients and those undergoing bypass surgery at the same time, who have higher rates of re-hospitalization. Focusing on these high risk sub-groups may further reduce rates of readmission following AVR. In addition, among those hospitalized almost half were hospitalized within 30 days, indicating the need to monitor patients closely during this period of heightened risk.

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Elders Requiring Fewer Hospital Days After Aortic Valve SurgeryMedicalResearch.com Interview with:Karthik Murugiah MBBSFellow in Cardiovascular Medicine Yale School of MedicineCenter for Outcomes Research and Evaluation (CORE) New Haven, CT 06510

Medical Research: What recommendations do you have for future research as a result of this study?Response: As a large proportion of the hospitalized patients were hospitalized within the first 30 days it indicates the potential to improve post op care, discharge practices and transition in care. However, in order to develop targeted interventions, further research is needed to illuminate the underlying reasons for hospitalization during this period in this particular population of patients.Citation:Trends in Hospitalizations Among Medicare Survivors of Aortic Valve Replacement in the United States From 1999 to 2010Karthik Murugiah, MD , Yun Wang, PhD, John A. Dodson, MD, Sudhakar V. Nuti, BA, Kumar Dharmarajan, MD, MBAa, b, Isuru Ranasinghe, MBChB, PhDa, Zack Cooper, PhD, Harlan M. Krumholz, MD, SMThe Annals of Thoracic SurgeryAvailable online 16 December 2014

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Time Means Brain! Fast Treatment for Acute Ischemic Stroke Improves RecoveryMedicalResearch.com Interview with:Diederik Dippel MD, PhDSenior Consultant in NeurologyErasmus MCUniversityMedical Center Rotterdam The Netherlands


Dr. Dippel: MR CLEAN is the first randomized clinical trial to show that intra-arterial treatment of ischemic stroke to get the clot out, really works. It leads to more recovery and less handicap. Previous studies had shown that intra-arterial treatment leads to recanalization, but the final proof that the treatment leads to recovery more often than standard treatment was lacking.With standard treatment, less than 1 out of 5 recovers without handicap, but with this new treatment, this will be 1 out of 3. The treatment did not lead to more complications than standard treatment. The rate of symptomatic intracranial hemorrhage was similar in both arms.Our study differs from previous, neutral trials.First, we required patients to have an intracranial arterial occlusion confirmed by neuro-imaging.Second, we used third generation thrombectomy devices, such as retrievable stents in most of the cases.Third, our trial was conducted in a country with a very good infrastructure, which allowed rapid transfer to intervention centers, which are spread throughout the country. Our rate of iv tPA in Dutch hospitals is over 11% on average.Last, all intervention centers participated, and almost no patients were treated outside the trial. Moreover, reimbursement of the treatment was conditional on participation in the trial. Medical Research: What should clinicians and patients take away from your report?Dr. Dippel: Intra-arterial treatment for acute ischemic stroke in patients with a confirmed intracranial occlusion of the anterior circulation, who can be treated within 6 hours from onset, is safe and effective. Confirmation of the occlusion should be done with MRA or CTA. Intra-arterial treatment should be started as soon as possible. Time is brain!We were very happy that we could show that the treatment works at least as well in elderly people, even in those over 80 years. We also had proof that the treatment works in patients with what at first appears to be a mild stroke, but often turns out to be al large one if you do not treat.

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Time Means Brain! Fast Treatment for Acute Ischemic Stroke Improves RecoveryMedicalResearch.com Interview with:Diederik Dippel MD, PhDSenior Consultant in NeurologyErasmus MCUniversityMedical Center Rotterdam The Netherlands

Medical Research: What recommendations do you have for future research as a result of this study?Dr. Dippel: Still more studies like MR CLEAN need to be done, we would like to have our findings confirmed. We need to determine the relationship between time since onset and effect of the treatment and we certainly need to find out which additional medication, such as antiplatelet agents and anticoagulants should be given and when this should be done. There is a large gap between the chances of recanalization on the one hand, and the chance of good recovery on the other. We need to close that gap. This will require efforts in basic and in clinical research. There is a lot of work ahead of us.Citation:A Randomized Trial of Intraarterial Treatment for Acute Ischemic StrokeOlvert A. Berkhemer, M.D., Puck S.S. Fransen, M.D., Debbie Beumer, M.D., Lucie A. van den Berg, M.D., Hester F. Lingsma, Ph.D., Albert J. Yoo, M.D., Wouter J. Schonewille, M.D., Jan Albert Vos, M.D., Ph.D., Paul J. Nederkoorn, M.D., Ph.D., Marieke J.H. Wermer, M.D., Ph.D., Marianne A.A. van Walderveen, M.D., Ph.D., Julie Staals, M.D., Ph.D., Jeannette Hofmeijer, M.D., Ph.D., Jacques A. van Oostayen, M.D., Ph.D., Geert J. Lycklama Nijeholt, M.D., Ph.D., Jelis Boiten, M.D., Ph.D., Patrick A. Brouwer, M.D., Bart J. Emmer, M.D., Ph.D., Sebastiaan F. de Bruijn, M.D., Ph.D., Lukas C. van Dijk, M.D., L. Jaap Kappelle, M.D., Ph.D., Rob H. Lo, M.D., Ewoud J. van Dijk, M.D., Ph.D., Joost de Vries, M.D., Ph.D., Paul L.M. de Kort, M.D., Ph.D., Willem Jan J. van Rooij, M.D., Ph.D., Jan S.P. van den Berg, M.D., Ph.D., Boudewijn A.A.M. van Hasselt, M.D., Leo A.M. Aerden, M.D., Ph.D., Ren J. Dallinga, M.D., Marieke C. Visser, M.D., Ph.D., Joseph C.J. Bot, M.D., Ph.D., Patrick C. Vroomen, M.D., Ph.D., Omid Eshghi, M.D., Tobien H.C.M.L. Schreuder, M.D., Roel J.J. Heijboer, M.D., Koos Keizer, M.D., Ph.D., Alexander V. Tielbeek, M.D., Ph.D., Heleen M. den Hertog, M.D., Ph.D., Dick G. Gerrits, M.D., Renske M. van den Berg-Vos, M.D., Ph.D., Giorgos B. Karas, M.D., Ewout W. Steyerberg, M.D., Ph.D., H. Zwenneke Flach, M.D., Henk A. Marquering, Ph.D., Marieke E.S. Sprengers, M.D., Ph.D., Sjoerd F.M. Jenniskens, M.D., Ph.D., Ludo F.M. Beenen, M.D., Ren van den Berg, M.D., Ph.D., Peter J. Koudstaal, M.D., Ph.D., Wim H. van Zwam, M.D., Ph.D., Yvo B.W.E.M. Roos, M.D., Ph.D., Aad van der Lugt, M.D., Ph.D., Robert J. van Oostenbrugge, M.D., Ph.D., Charles B.L.M. Majoie, M.D., Ph.D., and Diederik W.J. Dippel, M.D., Ph.D. for the MR CLEAN InvestigatorsN Engl J Med 2015; 372:11-20January 1, 2015DOI: 10.1056/NEJMoa1411587

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Unmet Material Needs May Lead To Poor Diabetes ControlMedicalResearch.com Interview with:Seth A.Berkowitz,MD, MPHDivision of General Internal MedicineMassachusetts General Hospital, Boston


Dr. Berkowitz: Prior studies had looked the association between single unmet basic material needs and diabetes control, but hadnt necessarily looked at multiple things people may not be able to afford, which more closely mirrors real-life. Also, prior studies had been done in a pre-Affordable Care Act setting, while, by being in Massachusetts, our study was conducted in a setting of near-universal healthcare coverage that is similar to what the rest of the US is moving towards. We found that difficulties meeting basic material needs, such as difficulties affording food, known as food insecurity, and having financial barriers to taking medications, called cost-related medication underuse, are associated with worse diabetes control and increased use of costly health services in diabetes patients, despite near-universal health insurance coverage Medical Research: What should clinicians and patients take away from your report?Dr. Berkowitz: Historically, patients come in for office visits or hospitalizations, but the majority of their time, the majority of the time that determines their health, is spent outside the healthcare system. Healthcare systems are increasingly being held accountable for health outcomes, but these outcomes may be determined by situations that most healthcare systems have limited experience in dealing with. This study, and the body of literature on what are sometimes called social determinants of health suggest that simply increasing access to healthcare that does not address root causes of illness may be missing a big piece of what patients need to stay healthy and manage their illnesses.Despite insurance coverage, unmet basic needs were common, associated with worse diabetes control, and high use of expensive health services. If we do not try to address these needs specifically, we may make little progress in improving health for vulnerable diabetes patients.

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Unmet Material Needs May Lead To Poor Diabetes ControlMedicalResearch.com Interview with:Seth A.Berkowitz,MD, MPHDivision of General Internal MedicineMassachusetts General Hospital, Boston

Medical Research: What recommendations do you have for future research as a result of this study?Dr. Berkowitz: Because healthcare systems often have little experience in helping patients meet material needs, there is a lot we still dont know.First and foremost, we dont actually know whether helping patients meet material needs will improve their health. We think it should, but this needs to be tested.Secondly, we need to determine what approaches work bestlinking patients with existing community resources, more generous prescription drug coverage, providing nutritious food, etc. Also, we need to know who can do this effectively and efficientlya community health worker, a resource specialist within a clinic, a case manager?Citation:Berkowitz SA, Meigs JB, DeWalt D, et al. Material Need Insecurities, Control of Diabetes Mellitus, and Use of Health Care Resources: Results of the Measuring Economic Insecurity in Diabetes Study. JAMA Intern Med. Published online December 29, 2014. doi:10.1001/jamainternmed.2014.6888.

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Non-Small Cell Lung Cancer: Stereotactic Radiation Plus Chemo Improved SurvivalMedicalResearch.com Interview with:Dr. Puneeth Iyengar, MD, PhD.Assistant Professor Director of Clinical ResearchDept of Radiation Oncology Co-leader, Thoracic Disease Oriented Team Harold Simmons Cancer CenterUT Southwestern Medical Center Dallas, TZ

Medical Research: What is the background for this study? What are the main findings?Response: Stage IV Non-small cell lung cancer (NSCLC) remains a disease of limited survival, in the range of one year for a majority of patients who historically have gone on to receive systemic therapy only. Disease in this patient population most often recurs in the sites of original gross disease. With greater understanding of the biology and patterns of failure that occur in stage IV NSCLC, it is becomingly increasingly obvious that there are subsets of patients, those with limited sites of metastatic disease, who may benefit with more aggressive local therapy in addition to systemic agents to effectuate longer progression free survival (PFS) and potentially overall survival (OS). Since failures of treatment occur most commonly in original gross deposits, local non-invasive therapy in the form of stereotactic body radiation therapy (SBRT) may offer a means to curtail the recurrences, perhaps as a way to shift the time to and patterns of failure.To address these concepts, a multi institutional single arm phase II study was conducted at UT Southwestern Medical Center in Dallas and University of Colorado Medical Center. Twenty-four patients with limited metastatic NSCLC (fewer than or equal to six sites of disease including the primary) who had progressed through at least one systemic therapy regimen were treated with SBRT to all sites of gross disease and the EGFR inhibitor erlotinib with progression free survival the primary end point. The results of the study were very significant, with a PFS in this study cohort of 14.7 months, compared to historical ranges of 2-4 months, and an OS of 20.4 months, compared to historical ranges of 6-9 months for this same patient population. The SBRT treatments were found to be very safe and efficacious only 3 out of 47 measurable lesions irradiated recurred with a concomitant shift in failure patterns from local to distant sites. As importantly, EGFR status was evaluated in 13 patient tumors, with none harboring the most common mutations. One could, therefore, predict that with a mutation enriched population, the combination of EGFR inhibitor and SBRT may have offered even greater PFS and OS benefits. Our observations also suggest that the SBRT treatments probably contributed the most to the dramatic PFS and OS outcomes.These findings were published in the Journal of Clinical Oncology in the December 1, 2014 print issue with an accompanying editorial.

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Non-Small Cell Lung Cancer: Stereotactic Radiation Plus Chemo Improved SurvivalMedicalResearch.com Interview with:Dr. Puneeth Iyengar, MD, PhD.Assistant Professor Director of Clinical ResearchDept of Radiation Oncology Co-leader, Thoracic Disease Oriented Team Harold Simmons Cancer CenterUT Southwestern Medical Center Dallas, TZ

Medical Research: What should clinicians and patients take away from your report? What recommendations do you have for future research as a result of this study?Response: Non-invasive local treatments likestereotactic body radiation therapy may have a significant role in altering the stage IV NSCLC disease course by offering hope for better PFS and even potentially OS outcomes. SBRT in our study was able to delay time to progression when compared to historical findings and was also able to change patterns of failure, from local to distant sites. Ultimately,stereotactic body radiation therapy may offer a very important therapeutic contribution to the overall management of limited metastatic NSCLC patients.

Our group has proposed a larger study, a phase II randomized trial, that hopes to compare SBRT used after first line therapy plus sequential maintenance therapy versus maintenance therapy alone for limited metastatic NSCLC patients. Similar trials have begun in Europe, suggesting a widespread effort to determine how beneficial local therapies, in the form of SBRT, may be to the metastatic disease state.Citation:Phase II Trial of Stereotactic Body Radiation Therapy Combined With Erlotinib for Patients With Limited but Progressive Metastatic Non-Small-Cell Lung CancerPuneeth Iyengar, Brian D. Kavanagh, Zabi Wardak, Irma Smith, Chul Ahn, David E. Gerber, Jonathan Dowell, Randall Hughes, Ramzi Abdulrahman, D. Ross Camidge, Laurie E. Gaspar, Robert C. Doebele, Paul A. Bunn, Hak Choy, and Robert TimmermanJCO Dec 1, 2014:3824-3830; published online on October 27, 2014;

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Collagen Target May Lead To Treatment Of Wounds, Wrinkles and Fragile SkinMedicalResearch.com Interview with:David Granville, BSc, PhD, FAHAProfessor,University of British ColumbiaScholar of the Royal Society of CanadaDirector, GEM Facility, Centre for Heart Lung Innovation, St. Pauls Hospital Founder and CSO, viDA Therapeutics, Inc.

Medical Research: What is the background for this study? What are the main findings?Dr. Granville: My background is in cardiovascular research. In particular, how age affects blood vessels and how age affects mechanisms of blood vessel and heart injury and repair. We became interested in skin aging during a study in which we were studying the role of a protein degrading enzyme known as Granzyme B in atherosclerosis (hardening of the arteries) and aging. In these studies, we were using a genetic mouse model that is prone to accelerated aging, and knocked out Granzyme B. Although we were initially focused on the blood vessels, we alsofound that Granzyme B-deficient mice exhibited younger-looking skin. As we started to look into this, we became aware that UV light can induce the skin cells to produce Granzyme B. As sunlight is believed to be responsible for 80-90% ofpreventable skin aging, we generated a solar-simulated light box (with the similar ratios of UVA/UVB to sunlight)to assess whetherGranzyme B played a role in UV-induced skin aging (aka photoaging). We exposed the mice to repetitive, low dose UV three times per week for 20 weeks. After 20 weeks we observed that Granzyme B deficient mice exhibited fewer wrinkles. We then wanted to look histologically and biochemically into how Granzyme B was affecting skin morphology. Granzyme B deficient mice exhibited greater collagen density compared to mice that possessed Granzyme B. As we looked into the mechanism in more detail, we determined that Granzyme B was cleaving a protein known as decorin. Decorin is responsible for collagen fibrillogenesis and assembling collagen into tight bundles. Loss of decorin is associated with a loss of collagen tensile strength. Interestingly, decorin also protects collagen from destruction by a protein-degrading enzyme known as MMP1. We showed in the study that by breaking down decorin, Granzyme B renders collagen susceptible to MMP1-mediated degradation. In addition, we showed that Granzyme B-fragmentation of another protein, fibronectin, led to the upregulation of MMP1 in skin fibroblasts. In summary, the paper showed that UV induced Granzyme B expression in the skin and showed that this enzyme contributes to the breakdown of extracellular matrix proteins and formation of wrinkles.A link to the Aging Cell publication: http://onlinelibrary.wiley.com/doi/10.1111/acel.12298/pdf


Medical Research: What should clinicians and patients take away from your report?Dr. Granville: While the media and public tend to focus on the perhaps the most obvious cosmetic implications of our findings, we believe Granzyme B plays a pathologic role (ie. clinically) in the skin in the impairment of tissue injury and repair. By preventing Granzyme B our work suggests that we can improve tissue repair/remodelling and increase the integrity and tensile strength of skin. This could have large implications with respect to skin thinning and skin tearing that is highly prevalent in the elderly and long-term care facilities. Our priorstudies also suggest a role in chronic wound healing (ie. diabetic wound healing, pressure ulcers/bed sores). I am also working with viDA Therapeutics to develop Granzyme B inhibitors for topical applications. Granzyme B is highly elevated in a number of autoimmune skin conditions. One in particular that we are quite excited about is discoid lupus erythematosus (DLE). Granzyme B is abundant in DLE. Given DLE is often induced and/or promoted by sunlight and involves scarring, hair loss, microvascular damage and other features where we know Granzyme B plays a role, we believe there is a high liklihood that we could modify/reduce the formation of scarring in these patients. viDA is anticipating clinical trials to commence by the end of 2016.


Medical Research: What recommendations do you have for future research as a result of this study?Dr. Granville: Obviously avoidance of sunlight is the best way to prevent skin aging/damage, but sometimes it is unavoidable. Likewise, we also have evidence that repetitive exposure to smoking can induce the expression of Granzyme B. Our future research is focused on further validating Granzyme B as a therapeutic target and developing drugs to prevent skin damage and restore skin (and other tissue)integrity.Citation:Parkinson, L. G., Toro, A., Zhao, H., Brown, K., Tebbutt, S. J. and Granville, D. J. (2014), Granzyme B mediates both direct and indirect cleavage of extracellular matrix in skin after chronic low-dose ultraviolet light irradiation. Aging Cell. doi:10.1111/acel.12298

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Structure of EV-D68 Common Respiratory Virus DelineatedMedicalResearch.com Interview with:Michael G. Rossmann PhDHanley Professor of Biological Sciences Hockmeyer Hall of Structural BiologyPurdue University,West LafayetteIN


Dr. Rossmann: My laboratory has long been interested in the structure of viruses and especially of Picornaviruses (e.g. EV-D68). We published the first 3D, near atomic resolution map of any animal virus in 1985. That was of Human Rhino (common cold) virus serotype 14. We then went on to show where and how the virus would bind to cellular receptors and also how certain small capsid binding compounds inhibited the viral infectivity. The latter was a collaboration first with the Sterling Winthrop company and later with ViroPharma. Thus our work on EV-D68 is a direct continuation of my interest in picornaviruses.Medical Research: What should clinicians and patients take away from your report?Dr. Rossmann: The pleconaril compound (or derivatives of it) that we (in collaboration with ViroPharma) developed against common cold viruses is likely to be an effective inhibitor of EV-D68, the causative agent of childhood respiratory sickness.Medical Research: What recommendations do you have for future research as a result of this study?Dr. Rossmann: Structural and functional analyses of recent isolates of the virus.Citation:Structure and inhibition of EV-D68, a virus that causes respiratory illness in childrenYue Liu, Ju Sheng, Andrei Fokine, Geng Meng, Woong-Hee Shin, Feng Long, Richard J. Kuhn, Daisuke Kihara, and Michael G. RossmannScience 2 January 2015: 347 (6217), 71-74. [DOI:10.1126/science.1261962]

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Risk of Breast Cancer in Women With Atypical Hyperplasia Better DefinedMedicalResearch.com Interview with:Dr. Lynn C. Hartmann MDProfessor of Oncology, Mayo ClinicAssociate Director for Education of the Mayo Clinic Cancer Center.


Dr. Hartmann: Women with atypical hyperplasia of the breast which is defined via breast biopsy that was done to evaluate findings on a mammogram or a palpable concern have been considered a high risk group of women, but the extent of their risk has not been clearly defined. As a consequence, practice guidelines for high-risk women (eg for screening MRI) do not include them. Mayo Clinic has developed a cohort of women with atypical hyperplasia who have been followed long-term for later breast cancers and we show that their risk of developing breast cancer is about 30% at 25 years of follow-up. This same level of risk was confirmed in the other large cohort of women with atypical hyperplasia, based at Vanderbilt University (Nashville Breast Cohort). This level of risk meets the current criterion for screening MRI and should also encourage the use of anti-estrogen drugs, such as tamoxifen, which have already been shown to be efficacious in this population of women.


Medical Research: What should clinicians and patients take away from your report?Dr. Hartmann: There are about 100,000 US women each year diagnosed with atypical hyperplasia via breast biopsy. Although strictly speaking, atypical hyperplasia is a benign finding, it is associated with a sizable risk of a later breast cancer. Physicians from numerous disciplines care for women with high-risk benign breast issues, including gynecologists, family physicians, internists, surgeons and oncologists. These practitioners, and the patients themselves, need information about the absolute risk of breast cancer occurring over time after a diagnosis of atypical hyperplasia. This information is provided in the NEJM report. Also, current guidelines should be updated to include this high-risk population and specifics about their absolute risk, and that the risk level qualifies these patients for screening MRI.Moreover, from the standpoint of risk reduction, four previously conducted breast cancer prevention trials included women with atypical hyperplasia. These trials used hormonal therapies (anti-estrogens) and showed that, in women with atypical hyperplasia, the use of such medications could lower the risk of a later breast cancer by 50% or more. Yet, other research has shown that women are quite reluctant to take such medications, primarily because of fear of side effects. In the NEJM report, we detail specific numbers of side effects that actually occurred in women who used these anti-estrogens (as opposed to the number of side effects seen in women taking placebo) and show that most of the side effects occurred quite uncommonly. Thus, we hope that the combination of information provided in this report on (i) actual risks of breast cancer and (ii) actual risks of side effects will help patients and practitioners make informed decisions on the best treatment approaches for women with atypical hyperplasia.


Medical Research: What recommendations do you have for future research as a result of this study?Dr. Hartmann: First, women with atypical hyperplasia should be included in future prospective trials of novel imaging strategies (they were not included in trials of MRI, which had been limited to women with hereditary risk).Second, efforts should continue to predict which women with atypical hyperplasia are at highest risk, especially in the first 5-10 years after their biopsy, so they can be cared for optimally. Our research team, and others, continue to study the underlying molecular pathways that drive the progression from atypical hyperplasia to cancer; identifying such processes would not only aid in risk prediction but also identify driving pathways that could be blocked pharmaceutically.Citation:Lynn C. Hartmann, Amy C. Degnim, Richard J. Santen, William D. Dupont, Karthik Ghosh. Atypical Hyperplasia of the Breast Risk Assessment and Management Options. New England Journal of Medicine, 2015; 372 (1): 78 DOI: 10.1056/NEJMsr1407164

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.COPD: Most Hospital Readmissions Not Due To COPDMedicalResearch.com Interview with:Tina Shah, MD University of Chicago MedicineDepartment of Pulmonary and Critical CareUniversity of Chicago

Medical Research: What is the background for this study? What are the main findings?Dr. Shah: The reason why we undertook this study is to better understand the Medicare COPD population that falls under the purview of the CMS Hospital Readmissions Reduction Program (HRRP). This program places up to a 3% penalty on all Medicare revenues for hospitals that take care of beneficiaries should a hospital exceed its expected readmission rate. Previously 30 day readmissions after index admissions for congestive heart failure, acute myocardial infarction and pneumonia fell subject to the HRRP. As of October 2014, COPD has been added to the list, despite minimal evidence to guide hospitals in how to curb COPD readmissions. The goal of this research was to provide an epidemiological background for this population and identify trends as a hypothesis generating first step to predict who is most likely to be readmitted and to identify targets for successful future interventions on this group. Our study population is unique in that we longitudinally look at about 1/2 of all Medicare admissions for COPD exacerbations, using the CMS guideline definition which is based on discharge ICD-9 codes. As described in previous literature, there is a large discrepancy between identification of COPD by provider versus coding algorithm, however since theHospital Readmissions Reduction Program is based on discharge coding it is important to examine this particular group.

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.COPD: Most Hospital Readmissions Not Due To COPDMedicalResearch.com Interview with:Tina Shah, MD University of Chicago MedicineDepartment of Pulmonary and Critical CareUniversity of Chicago

Dr. Shah: Our paper has 3 main findings:First, Although COPD was the leading cause of rehospitalization within 30 days of an initial index admission, the majority of readmissions were not due to COPD and include a wide array of reasons.Second, patients who used post-acute care, including home care and skilled nursing facilities were readmitted for different reasons than those who were discharged to home.Third, patients who were readmitted were likely to be dually eligible for Medicare and Medicaid, posing the potential for a disproportionately high penalty on hospitals who care for a large percentage of patients who are generally sicker, poorer and have less community access to health resources. This finding adds to the growing concern in other literature about the lack of standardization by socioeconomic status in the current penalty.The application of this studys findings for clinicians and patients is a better understanding of the patient related factors including dual eligibility status that are associated with a higher risk of readmission and to take a closer look at the use and appropriate triage of patients to levels of care upon discharge. Our study highlights a need for research looking into the role of post acute care on readmissions, a next area of investigation that our research group is undertaking.Citation:Understanding why copd patients get readmitted: a large national study to delineate the medicare population for the readmissions penalty expansionPublished online December 24, 2014.Shah T, Churpek MM, Coca Perraillon M, Konetzka R. doi:10.1378/chest.14-2181.

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Cholera Bacteria Kills Neighbors To Acquire Antibiotic Resistance GenesMedicalResearch.com Interview with:Melanie Blokesch PhD AssistantProfessor (tenure-track)Laboratory of Molecular MicrobiologyGlobal Health Institute,School of Life SciencesSwiss Federal Institute of Technology Lausanne (EPFL) Lausanne Switzerland

Medical Research: What is the background for this study? What are the main findings?Dr. Blokesch: We have been studying the cholera-causing bacteriumVibrio cholerae for many years in my laboratory. Our main focus has always been on elucidating how this pathogen acquires new genetic material that allows it to evolve. This is often accomplished through a mechanism known as horizontal gene transfer (HGT). There are three main modes ofhorizontal gene transfer in bacteria and the one we are primarily interested in is called natural competence for transformation. When the bacterium enters the state of natural competence it can take up free genetic material from its surrounding and in case it recombines this new material into its own genome the bacterium is considered to be naturally transformed. Notably, natural competence/transformation was first described in 1928 by Fred Griffith, who showed that transformation can render harmless bacteria pathogenic. These early experiments can be considered a milestone in molecular biology as it later led to the discovery of DNA as the carrier of genetic information.Medical Research: What are the main findings?

Dr. Blokesch: The main finding of our study is that the pathogenV. cholerae does not solely rely on free DNA floating around but that it actively kills neighbouring bacteria followed by the uptake of their DNA. Indeed, we were able to show that the two processes killing of other bacteria and DNA uptake are co-regulated by the same proteins within the bacterial cell. We also used imaging techniques to visualize the killing of other bacteria by V. cholerae, followed by the release of their genetic material, which the predator then pulled into its own cell. We further quantified these HGT events by following the transfer of an antibiotic resistance gene from the killed bacterium to the predatory V. cholerae cell. Notably, the spread of antibiotic resistances is a major health concern and HGT is a major driver of it.


Medical Research: What should clinicians and patients take away from your report?Dr. Blokesch: There is still a long way to go until we fully understand this process and can act accordingly. However, another important finding of our study was that the killing device (and the DNA uptake machinery) was triggered by a natural polysaccharide, chitin, which is the most abundant polymer in aquatic environments (e.g, it makes up the shell/exoskeleton of small crustaceans). Indeed, V. cholerae is a natural inhabitant of such environments and is therefore primarily transmitted to humans by contaminated water. It is tempting to speculate that the bacteriums association with chitinous surfaces followed by the production of the killing device could render the bacteria more pathogenic when ingested by humans as it could kill the protective commensal bacteria in the human gut. Therefore, filtration methods that remove larger (chitinous) particles might be a good way to at least partially protect people from cholera infections. Indeed, such filtration studies have been performed by Rita Colwell (University of Maryland) and her collaborators in rural villages of Bangladesh. The scientists reported that folding sari cloth a few times followed by the filtration of water through them could remove V. cholerae bacteriaattached to particles and significantly lower the number of cholera patients in this endemic area.


Medical Research: What recommendations do you have for future research as a result of this study?Dr. Blokesch: There is so much we dont know yet about the causative agent of cholera even though the disease itself has been extensively studied over the last 100 years. Thus, in the future we and probably also others will focus on elucidating the environmental lifestyle of the pathogen. This will allow us to acquire new insights into cholera transmission and to better understand how an innocuous aquatic bacterium evolved towards being a dangerous human pathogen.Citation:The type VI secretion system of Vibrio cholerae fosters horizontal gene transferSandrine Borgeaud, Lisa C. Metzger, Tiziana Scrignari, Melanie BlokeschScience 2 January 2015:Vol. 347 no. 6217 pp. 63-67DOI: 10.1126/science.126006

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Healthy Lifestyle, Not Supplements, Linked to LongevityMedicalResearch.com Interview with:Annlia Paganini Hill PhDProject Scientist Biostatistician and EpidemiologistDepartment of Neurology, School of Medicine University of California, Irvine, Irvine, California

Medical Research: What is the background for this study? What are the main findings?Response: Free radicals are formed when one exercises and when the body converts food to energy. Environmental sources (e.g. smoke, air pollution, sunlight) also expose the body to free radicals. Free radicals can cause oxidative stress and damage cells. Oxidative stress is thought to play a role in a variety of diseases: cancer, cardiovascular disease, diabetes, Alzheimers disease, Parkinsons disease, cataracts, and age-related macular degeneration.Antioxidants are man-made or natural substances that may prevent or delay some types of cell damage. Antioxidants are found in many foods and are also available as dietary supplements. Vegetables and fruits are rich sources of antioxidants. There is good scientific evidence that eating a diet with lots of vegetables and fruits is healthful and lowers risks of certain diseases. However, it is unclear whether this is because of the antioxidants, something else in these foods, other foods in peoples diet, or other lifestyle choices.While antioxidants have been shown to counteract oxidative stress in cells and animal studies,whether consuming large amounts of antioxidant supplements benefits human health is debated. Given the continued use of vitamin supplements by a large proportion of the population and the presumed safety of antioxidant supplementation, we assessed the relationship between antioxidant vitamin intake and all-cause mortality in older adults.We examined these associations using data from the Leisure World Cohort Study, a study of nearly 14,000 residents of a California retirement community. In the early 1980s, participants (median age, 74 years) reported details on use of vitamin supplements and dietary intake of foods containing vitamins A and C. During followup (1981-2013), over 93% of participants had died (median age at death, 88 years).


Medical Research: What are the main findings?Response: Previously, we had found that a number of factors were associated with lower risk of death in our cohort not smoking, physical activity, moderate alcohol consumption, caffeine intake, ideal body mass index (neither too fat nor too thin), and no history of high blood pressure, angina, heart attack, stroke, diabetes, rheumatoid arthritis, or cancer .Neither dietary nor supplemental intake of vitamins A, C or E were significantly associated with reduced mortality in this study once these other lifestyle behaviors and disease conditions were taken into account.In Leisure World Cohort and in the general population, health-promoting habits often cluster; e.g. those who take vitamin supplements often exercise, do not smoke, and are not obese. Thus, these factors explain the observed association between longevity and vitamin supplements in our and previous studies.


Medical Research: What should clinicians and patients take away from your report?Response: Antioxidant supplements should not be used to replace a nutritionally adequate diet. A healthful diet characterized by high amounts of fruits and vegetables, whole grains, and fish should be recommended to avoid nutritional deficiencies and to prevent chronic disease.Additionally, other studies have shown that high-dose antioxidant supplements may even be harmful (increased risks of prostate cancer, hemorrhagic stroke, and lung cancer in smokers). And because antioxidant supplement may interact with other medications, use of supplements should be discussed with a health care provider.Citation:Antioxidant Vitamin Intake and Mortality: The Leisure World Cohort Study.Paganini-Hill A, Kawas CH, Corrada MM.Am J Epidemiol. 2014 Dec 29. pii: kwu294. [Epub ahead of print]

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Adenocarcinoma of Lung May Spread Through AirwaysMedicalResearch.com Interview with: Joao R. Inacio, MDCardiothoracic Radiologist Director Visiting Professor ProgramAssistant Professor of Radiology, University of OttawaMedical Imaging, The Ottawa Hospital Ottawa, ON


Dr. Inacio: Lung cancer is the most common and most lethal cancer worldwide. Its prognosis remains poor with a 5-year survival rate of 618%. Adenocarcinoma has surpassed squamous cell carcinoma as the leading histologic type. The presence of metastases carries the worst prognosis in lung cancer and is the most important in determining staging and management. Hematogenous spread (i.e., carried by blood) is the most common mechanism of intrapulmonary metastasis. Cumulative evidence suggests that intrapulmonary aerogenous spread may exist and is under recognized.Deriving from our clinical experience, we performed a literature review that supports the hypothesis that lung cancer, particularly adenocarcinoma, may spread through the airways. With aerogenous metastases, it has been postulated that cancer cells growing along the alveolar septa at the primary site detach from the basal membrane, spread through the airways and re-attach and grow along alveolar septa away from the primary focus.Radiology-pathology correlation studies, using Chest Computed Tomography (CT), have documented the radiological evolution from focal adenocarcinoma to multifocal airspace disease and demonstrated cytologic and histologic findings supportive of aerogenous spread.


Medical Research: What should clinicians and patients take away from your report?Dr. Inacio: The putative occurrence of intrapulmonary aerogenous metastasis of lung cancer has staging, management, and prognostic implications.This phenomenon has been described in primary lung adenocarcinoma, particularly those with invasive mucinous, papillary and micro-papillary subtypes.There are CT features that are suggestive of aerogenous spread, specifically persistent centrilobular nodules and branching opacities (tree-in-bud nodules). Nodules tend to be clustered and invariably grow on serial imaging, in some cases progressing to confluent airspace disease. When these features are found remote from a dominant lung lesion proven to be an adenocarcinoma, and/or in patients with a prior history of treated lung adenocarcinoma, intrapulmonary aerogenous spread should be suspected.Importantly, aerogenous metastases must be distinguished from multiple synchronous lesions in the spectrum of lung adenocarcinoma. A multidisciplinary approach, including clinicians, radiologists, thoracic surgeons, pathologists and geneticists is required to guide diagnosis and treatment in these cases. Genomic profiling may be beneficial in the future to prove monoclonality when aerogenous metastases are suspected.


Medical Research: What recommendations do you have for future research as a result of this study?Dr. Inacio: There is a need for prospective studies combining imaging, pathology and molecular studies to confirm the presence of this phenomenon and elucidate its impact on the prognosis of lung cancer patients.Future therapies might attempt to address some of the unique aspects of aerogenous dissemination. For instance, drugs targeting mechanisms involved in cancer cell shedding, anchorage-independent survival, and re-attachment in distant alveoli may hold promise. One could hypothesize inhalational therapy as a potential treatment to target the intra-alveolar nature of aerogenous metastases. K-Ras mutations and infiltration of tumor tissue by macrophages and neutrophils have been implicated in the pathogenesis of mucinous adenocarcinoma and aerogenous metastases. Pharmacologic agents modulating K-Ras activation and tumor-associated leukocyte interaction could prove beneficial in the prevention of aerogenous spread.Citation:Anand Gaikwad, Carolina A. Souza, Joao R. Inacio, Ashish Gupta, Harmanjatinder S. Sekhon, Jean M. Seely, Carole Dennie, Marcio M. Gomes. Aerogenous Metastases: A Potential Game Changer in the Diagnosis and Management of Primary Lung Adenocarcinoma. American Journal of Roentgenology, 2014; 203 (6): W570 DOI: 10.2214/AJR.13.12088

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Y Chromosome Mutation Can Lead To Sex Reversal and CancerMedicalResearch.com Interview with:Michael A. Weiss, MD, PhD and Joseph RaccaCase Western Reserve School of Medicine in Cleveland, Ohio.Medical Research: What is the background for this study? What are the main findings?

Response: The function of the gene responsible for male differentiation, sex-determining region of the Y chromosome (SRY), was first demonstrated in transgenic mouse models by P. Koopman, R. Lovell-Badge and colleagues in the early 1990s. These findings were corroborated by identification of mutations in human SRY that are associated with human sex reversal: XY, 46 gonadal dysgenesis leading to somatic sex reversal (Swyers Syndrome). Such mutations may occur spontaneously in spermatogenesis or be inherited. The characterization of the molecular defects associated with these mutations has unmasked novel biological and biochemical activities of SRY. More broadly, such studies have also increased our understanding of an entire family of related transcription factors (Sry-box related; SOX), which broadly function in metazoan development (from worms, fish and flies to mammals). Within human SRY, the majority of clinical mutations occur in the region of the protein responsible for specific DNA binding and DNA bending, the primary molecular actions of SRY at target genes. Our study bridges structure (i.e., protein folding and stability) and function (i.e., transcriptional activation of target genes and related cell-biological processes such as trafficking and proteosomal degradation).In our current study, we highlighted the importance of a structural scaffold in human SRY, specifically a key single amino acid that buttresses the unique L-shape structure of this domain. The mutation of interest represents a perfect storm leading to deleterious effects on multiple activities, including specific DNA binding, cellular localization, and both protein and cellular stability (lifetime), among other properties, together leading to sex reversal and cancer (gonadoblastoma) in the proband patient. Our integrated multi-disciplinary approach allowed us to characterize these various facets of SRY in the context of its biological site of action: the pre-Sertoli cell in an embryonic gonadal ridge just prior to its morphological differentiation into a testis. We are grateful to Prof. Patricia K. Donahoe (Harvard Medical School and the Massachusetts General Hospital), who generously provided this micro-dissected pre-Sertoli cell line.

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Y Chromosome Mutation Can Lead To Sex Reversal and CancerMedicalResearch.com Interview with:Michael A. Weiss, MD, PhD and Joseph RaccaCase Western Reserve School of Medicine in Cleveland, Ohio.Medical Research: What should clinicians and patients take away from your report?Response: Mutations in SRY associated with sex reversal may coincide with the formation of gonadoblastoma, pediatric malignancy containing a solid mass of undifferentiated cells types.Although patients harboring mutations in SRY may exhibit a continuum of phenotypes, all XY sex-reversed females are sterile. The XY gonads are intra-abdominal, scarred and prone to cancer. On microscopic examination, such gonads lack differentiated features of either testes or ovaries. In childhood, such patients will otherwise grow normally as girls. At the onset of puberty, however, the XY child will not begin to have periods (primary amenorrhea); pubic hair and breast development is typically within the normal range.An important aspect of this study is the use of an integrated approach to probe the molecular functions of SRY. Due to the location of this mutation (within the DNA-binding domain), it might have been annotated as simply a DNA binding defect. Such a domain-based annotation would have missed the perfect storm of perturbations to the cellular biochemistry of the protein and general biophysical importance of the general aromatic-buttress motif in the overall SOX family of transcription factors. Our integrated and multi-disciplinary approach revealed multiple facets of structure and function. The editors of The Journal of Biological Chemistry highlighted this study as a Paper of the Week in light of such beautiful facets: the findings highlight the utility of clinical mutations as key experiment of nature to probe the subtle inter-relation of structure, function and phenotype that underlies developmental gene regulation.

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Y Chromosome Mutation Can Lead To Sex Reversal and CancerMedicalResearch.com Interview with:Michael A. Weiss, MD, PhD and Joseph RaccaCase Western Reserve School of Medicine in Cleveland, Ohio.Medical Research: What recommendations do you have for future research as a result of this study?Response: As previously mentioned, this location of this mutation is within the DNA binding and bending region of human SRY and this region also harbors the majority of sex reversal mutations. What this particular mutation taught was that these mutations are nature-designed probes for structure-functions studies. Furthermore, we have undertaken studies of inherited mutations to study how subtle defects in SRY can lead to two different developmental outcomes. Our ongoing studies of candidate SRY mutations are providing molecular insights into mechanistic details of how this protein functions as a switch in development. Also, our over-arching general concepts will (with regard to specific DNA binding and bending and conserved cellular functions), as we believe, relate to the entire family of related transcription factors.Citation:Structure-Function Relationships in Human Testis-determining Factor SRY: AN AROMATIC BUTTRESS UNDERLIES THE SPECIFIC DNA-BENDING SURFACE OF A HIGH MOBILITY GROUP (HMG) BOXJoseph D. Racca, Yen-Shan Chen, James D. Maloy, Nalinda Wickramasinghe, Nelson B. Phillips, and Michael A. Weiss Biol. Chem. 2014 289: 32410-32429. First Published on September 24, 2014, doi:10.1074/jbc.M114.597526

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Whole Grains Linked To Lower Cardiac and Overall MortalityMedicalResearch.com Interview with: Qi Sun, MD ScDAssistant Professor of Medicine Channing Division of Network MedicineBrigham and Womens Hospital and Harvard Medical School, Assistant Professor, Department of NutritionHarvard School of Public Health Boston, MA 02115


Dr. Sun: While we know whole grains are beneficial for reducing the risk of some major chronic diseases, such as heart disease and diabetes, evidence regarding whether whole grains are also able to lower mortality is sparse. We therefore want to answer this important research question in the current analysis. Using data collected from two prospective cohort studies consisted of more than 100 thousand US men and women, we found that whole grain intake was significantly associated with lower total mortality and lower cardiovascular mortality, but not cancer mortality. For every serving (28 grams) of whole grain intake per day, the total mortality is reduced by 5% and cardiovascular mortality by 9%.Medical Research: What should clinicians and patients take away from your report?Dr. Sun: Whole grains should be recommended to replace refined carbohydrate, such as white bread, white rice, and sugar-sweetened beverages, to help lower the risk of developing heart disease, diabetes, and premature death.Medical Research: What recommendations do you have for future research as a result of this study?Dr. Sun: Future research may focus on understanding the mechanisms, especially the active ingredients in whole grains, that account for the beneficial effects of whole grains. In addition, we need to understand whether whole grain consumption can especially benefit people with certain characteristics, including genetic susceptibility and other risk profiles.Citation:Wu H, Flint AJ, Qi Q, et al. Association Between Dietary Whole Grain Intake and Risk of Mortality: Two Large Prospective Studies in US Men and Women. JAMA Intern Med. Published online January 05, 2015. doi:10.1001/jamainternmed.2014.6283.Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.No Link Between HPV Vaccine and Multiple SclerosisMedicalResearch.com Interview with:Anders Hviid, M.Sc., Dr.Med.Sci.Senior Investigator, Statens Serum Institut

Medical Research: What is the background for this study?

Response: After the widespread introduction of HPV vaccination of adolescent girls, a number of safety concerns have emerged. In this case, demyelinating diseases, including multiple sclerosis, occurring after HPV vaccination has been reported in social media, news media and medical journals.Medical Research: What are the main findings?Response: In a study of almost 4 million Danish and Swedish women, we found no support for an increased risk of multiple sclerosis or other demyelinating diseases following HPV vaccination. Medical Research: What should clinicians and patients take away from your report?Response: In this the largest and most comprehensive study to date, there was no support for this particular safety concern. The current evidence suggests that clinicians and patients should not fear demyelinating diseases as a result of HPV vaccination.Medical Research: What recommendations do you have for future research as a result of this study?Response: Vaccine safety issues continue to arise. To maintain professional and public trust in routine immunization programs, it is important to address these issues in a timely manner with high quality research.Citation:Langer-Gould A, Qian L, Tartof SY, et al. Vaccines and the Risk of Multiple Sclerosis and Other Central Nervous System Demyelinating Diseases. JAMA Neurol. 2014;71(12):1506-1513. doi:10.1001/jamaneurol.2014.2633.

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Disruptive Gastrointestinal Problems Common In Infants and ToddlersMedicalResearch.com Interview with:Miranda van Tilburg, PhDAssociate Professor of MedicineUniversity of North Carolina


Dr. van Tilburg: Functional gastrointestinal disorders are common in children, adolescents and adults but little is known about the prevalence in infants and toddlers. Functional gastrointestinal disorders in infancy include disorders such as regurgitation, colic, and dyschezia, while functional gastrointestinal disorders in toddlers include functional constipation, functional diarrhea, functional dyspepsia, cyclic vomiting, and rumination. Of these disorders only colic and regurgitation have received much research attention. Prevalence, cause and consequences of most functional gastrointestinal disorders in infants and toddlers are largely unknown. We set out to determine the prevalence in the US by asking a representative sample of mothers to report on their childs symptoms. Our study found that 27% of infants and toddlers may suffer from a functional gastrointestinal disorder. Among infants, regurgitation was the most common disorder and among toddlers constipation. Despite functional gastrointestinal disorders generally being more prevalent in older girls and adult women, no sex differences were found in this age group. Toddlers who suffer from a functional gastrointestinal disorders had lower quality of life and made more health care visits.Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Disruptive Gastrointestinal Problems Common In Infants and ToddlersMedicalResearch.com Interview with:Miranda van Tilburg, PhDAssociate Professor of MedicineUniversity of North Carolina

Medical Research: What should clinicians and patients take away from your report?Dr. van Tilburg: These findings indicate that functional gastrointestinal disorders affect more than 1 in 4 infants and toddlers, making it one of the most common disorders in this age group. These disorders have a measurable impact on quality of life and health care visits. Studying these conditions may improve the lives of a significant number of children.Medical Research: What recommendations do you have for future research as a result of this study?Dr. van Tilburg: These conditions are largely neglected in the scientific literature. For example in the past 15 year studies scientific publications on functional gastrointestinal disorders in children and adolescents have increased rapidly and new discoveries have been made about their causes, consequences and treatment. However, only a handful of studies focus on these disorders in infants and children. The results of the current study indicate that any study in these disorders will impact the lives of many children and their families. Given the paucity in existing research, we need studies on all aspects of these disorders.Citation:Prevalence of Functional Gastrointestinal Disorders in Infants and Toddlers Miranda A.L. van Tilburg, PhD Paul E. Hyman, MD Lynne Walker, PhD Audra Rouster, MD Olafur S. Palsson, PhD Sung Min Kim, BA William E. Whitehead, PhDThe Journal of Pediatrics Available online 31 December 2014

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Childhood Molluscum Contagiosum Can Last Up To Two YearsMedicalResearch.com Interview with:Jonathan OlsenInstitute of Primary Care and Public HealthCardiff University Heath Park Cardiff

MedicalResearch: What is the background for this study? What are the main findings?Response: Molluscum Contagiosum is a common skin condition in children which has a prevalence of between 5.1% to 8% in children aged 14 years and under. Strikingly however, there is little epidemiological evidence describing the natural history, transmission between family members and impact upon quality of life of molluscum contagiosum. Our research aimed to address this gap in evidence by conducting a prospective cohort study of UK children recruited by clinical and self-referral using the validated Molluscum Contagiosum Diagnostic Tool for Parents (MCDTP).We recruited 306 children during 2013 and showed that on average lesions will last for 12 months, however 30% still had lesions at 18 months and 13% still had lesions at 24 months. Most children experienced only a small effect on their quality of life from the condition, however 1 in 10 experienced a large or very large impact on their quality of life. The condition was shown to be highly contagious with further transmission between children living in the same household as an index case shown in 40%.

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Childhood Molluscum Contagiosum Can Last Up To Two YearsMedicalResearch.com Interview with:Jonathan OlsenInstitute of Primary Care and Public HealthCardiff University Heath Park Cardiff

MedicalResearch: What should clinicians and patients take away from your report?Response: For most children molluscum contagiosum will have only a small effect on their quality of life, however children with a greater number of lesions may experience a greater effect on their quality of life. Parents should be aware that there is risk of transmission to other children living in the household, however there is little evidence of whether steps can be taken to reduce this risk.The idea that molluscum contagiosum is always a benign, trivial illness needs to be challenged.MedicalResearch: What recommendations do you have for future research as a result of this study?Response: We recommend that treatment should be considered for children with the condition, in particular those experiencing a significant impact on their quality of life and with a more severe episode of the disease (larger number of lesions).In first instances a well conducted treatment trial should be conducted to assess the effects of therapeutic approaches.Citation:Time to resolution and effect on quality of life of molluscum contagiosum in children in the UK: a prospective community cohort studyJonathan R Olsen, MSc Prof John Gallacher, PhD, Prof Andrew Y Finlay, FRCP, Prof Vincent Piguet, FRCP, Nick A Francis, MRCGPThe Lancet Infectious Diseases Available online 23 December 2014

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Bariatric Surgery Linked To Lower Long Term MortalityMedicalResearch.com Interview with:David Arterburn, MD, MPH, FACP Associate Investigator Group Health Research Institute Seattle, WA 98101 andDavid L. Maciejewski PhD Center for Health Services Research in Primary CareDurham VA Medical Center, Durham, North Carolina

MedicalResearch.com: Why was this study needed?Response: There were several reasons to conduct this study. First, although complications and death during and soon after bariatric surgery have progressively declined over the past several decades, there is simply very little long-term evidence on the survival benefits of bariatric surgery in Americans having surgical procedures that are being used today in routine practice.Second, we felt that it was important to look at the impact of bariatric surgery among veterans because they represent an older male cohort often with multiple medical comorbidities, which is different from the typical bariatric patient in the United States, who is often younger and female.MedicalResearch.com: How was your study conducted?Response: We conducted a retrospective observational study using high-quality data from national Department of Veterans Affairs electronic databases and the VA Surgical Quality Improvement Program. We identified veterans who underwent bariatric surgery in VA medical centers from 2000 to 2011. Three quarters of them were men. We matched them to control patients using an algorithm that included age, sex, VA geographic region, body mass index (BMI), diabetes, and Diagnostic Cost Group. We then compared survival across bariatric patients and matched controls using Kaplan-Meier estimators and stratified, adjusted Cox proportional hazards analyses.

Read the rest of the interviews on MedicalResearch.comContent NOT an endorsement of efficacy and NOT intended as specific medical advice.Bariatric Surgery Linked To Lower Long Term MortalityMedicalResear

medicalresearch.com: medical research exclusive interviews january 7 2014

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