MedicalResearch.com Interview with:
Lee Zou, Ph.D.
Professor of Pathology, Harvard Medical School
The Jim & Ann Orr MGH Research Scholar
Associate Scientific Director, MGH Cancer Center
Medical Research: What is the background for this study? What are the main findings?
Dr. Lee Zou: Cancer cells must rely on telomerase or the alternative lengthening of telomere (ALT) pathway to maintain telomeres and bypass replicative senescence. The ALT pathway is active in about 10-15% of human cancers, and it is particularly prevalent in specific cancer types, such as osteosarcoma, glioblastoma, and neuroendocrine pancreatic tumors. ALT is a recombination-mediated process. Whether the reliance of cancer cells on alternative lengthening of telomere can be exploited therapeutically was not known.
In our study, we discovered that the ATR kinase is a key regulator of alternative lengthening of telomere. We found that ATR inhibitors disrupt ALT effectively. Furthermore, we found that ATR inhibitors selectively kill ALT-positive cancer cells in a panel of caner cell lines. These findings have suggested the first rational therapeutic strategy for the treatment of ALT-positive cancer. (more…)
MedicalResearch.com Interview Invitation
Dr. Eric Boersma
Associate Professor of Clinical Cardiovascular EpidemiologyThoraxcenter, Erasmus Medical Center and Cardiovascular Research Institute COEUR, Rotterdam, the NetherlandsMedicalResearch: What is the background for this study? What are the main findings?Dr. Boersma: Near-infrared spectroscopy (NIRS) is a novel intracoronary imaging technique.
The NIRS-derived lipid core burden index (LCBI) quantifies the lipid content within the coronary artery wall.
This study was designed to evaluate the prognostic value of LCBI in patients with coronary artery disease (CAD) undergoing coronary catheterization (CAG).
We learned that patients with high (above the median) LCBI values had 4 times higher risk of coronary events during 1 year follow-up than those with low values.
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MedicalResearch.com Interview with:
Soko Setoguchi, MD DrPH
Assistant Professor of Medicine
Harvard Medical School and Harvard School of Public Health
Director of Safety and Outcome Research in Cardiology
Associate Physician in the Division of Pharmacoepidemiology and Pharmacoeconomics Brigham and Women’s Hospital
Medical Research: What is the background for this study? What are the main findings?
Dr. Setoguchi: Medicare made a decision to cover Carotid Artery Stenting (CAS) in 2005 after publication of SAPPHIRE, which demonstrated the efficacy of Carotid Artery Stenting (CAS) vs Carotid endarterectomy (CEA) in high risk patients for CEA. Despite the data showing increased carotid artery stenting dissemination following the 2005 National Coverage Determination, peri-procedural and long-term outcomes have not been described among Medicare beneficiaries, who are quite different from trial patients, older and with more comorbidities in general population.
Understanding the outcomes in these population is particularly important in the light of more recent study, the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST), which established CAS as a safe and efficacious alternative to CEA among non-high-surgical risk patients that also expanded the clinical indication of carotid artery stenting.
Another motivation to study ‘real world outcomes in the general population is expected differences in the proficiency of physicians peforming stenting in trial setting vs. real world practice setting. SAPPHIRE and CREST physicians were enrolled only after having demonstrated CAS proficiency with low complication rates whereas hands-on experience and patient outcomes among real-world physicians and hospitals is likely to be more diverse.
We found that unadjusted mortality risks over study period of 5 years with a mean of 2 years of follow-up in our population was 32%. Much higher mortality risks observed among certain subgroups with older age, symptomatic patients and non-elective hospitalizations.
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MedicalResearch.com Interview with:
Dr. Jeanne Madden PhDInstructor, Department of Population Medicine
Harvard Medical School
Medical Research: What is the background for this study? What are the main findings?
Dr. Madden: When Medicare Prescription Drug Coverage started in 2006, many experts voiced concerns about disabled patients with serious mental illness making the transition from state Medicaid coverage to Medicare. Our study is one of the first to examine the impact of the transition in mentally ill populations. People living with schizophrenia and bipolar disorder are at high risk of relapse and hospitalization and are especially vulnerable to disruptions in access to their treatments.
We found that the effects of transitioning from Medicaid to Medicare Part D depended on where patients lived. Transition to Part D in states that put limits on Medicaid drug coverage resulted in fewer patients going without treatment.
By contrast, in states with more generous drug coverage, we saw reductions in use, of antipsychotics in particular, after patients shifted to Medicare Part D. This may have been due to new cost controls used within many private Medicare drug plans. Given that most states in the US are in this latter category, with the relatively generous Medicaid drug coverage, we also found reductions in antipsychotic use nation-wide.
Although a very large group of people made that transition from Medicaid to Medicare in 2006, thousands more still transition every year because when disabled people qualify for Medicare, they must wait 2 years for their benefits kick in. Also, many other disabled patients are on Medicaid only and don’t qualify for Medicare. They are of course affected by restrictions on Medicaid coverage, which vary from state to state.
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MedicalResearch.com Interview with:
Leora Horwitz, MD, MHS
Director, Center for Healthcare Innovation and Delivery Science
New York University Langone Medical Center
Director, Division of Healthcare Delivery Science
Department of Population Health, NYU School of Medicine
New York, NY 10016
Medical Research: What is the background for this study? What are the main findings?
Dr. Horwitz: We reviewed over 1500 discharge summaries from 46 hospitals around the nation that had been collected as part of a large randomized controlled trial (Telemonitoring to Improve Heart Failure Outcomes). All summaries were of patients who were admitted with heart failure and survived to discharge. We found that not one of them met all three criteria of being timely, transmitted to the right physician and fully comprehensive in content. We also found that hospitals varied very widely in their average quality. For instance, in some hospitals, 98% of summaries were completed on the day of discharge; in others, none were. In the accompanying Data Report, we show that summaries transmitted to outside clinicians and including more key content elements are associated with lower risk of rehospitalization within 30 days of discharge. This is the first study to demonstrate an association of discharge summary quality with readmission.
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MedicalResearch.com Interview with:
Armen K. Goenjian, M.D., L.D.F.A.P.A., F.A.C.G.S.
Research Professor of Psychiatry
Department of Psychiatry and Biobehavioral Sciences
David Geffen School of Medicine at UCLA
Medical Research: What is the background for this study?
Response: Post-traumatic stress disorder (PTSD) is a psychiatric disorder that develops after exposure to a traumatic event such as rape, war, natural disaster, and accident. Symptoms include recurrent intrusive traumatic memories, flashbacks, nightmares, hyper-vigilance, jumpiness, and anxiety.
Dopaminergic and serotonergic systems have been implicated in PTSD. Catechol-O-methyltransferase (COMT) is an enzyme that degrades dopamine, an important brain neuro-hormone that regulates human behavior, thoughts and emotions. Tryptophan hydroxylase is the rate limiting step in the synthesis of serotonin, another important neuro-hormone that regulates arousal, sleep, anxiety, and mood. This study evaluated the association of four COMT gene loci, and the joint effect of COMT and tryptophan hydroxylase 2 (TPH-2) genes on PTSD symptoms.
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MedicalResearch.com Interview with:
Paula Chu Doctoral candidate
Harvard University's Health Policy Program
Boston MAMedical Research: What is the background for this study? What are the main findings?Response: This study was borne out of a mutual interest in the effects of yoga and wellness in general between myself and my coauthors.
We had heard and read about yoga's effects on certain conditions like anxiety and pain, and we wanted to see if there was scientific evidence on yoga's impact on measurable physiological cardiovascular outcomes.(more…)
MedicalResearch.com Interview with:
Nenad Bursac PhD
Rooney Family Associate Professor of Biomedical Engineering
Associate Professor of Medicine Duke University
Medical Research: What is the background for this study? What are the main findings?Dr. Bursac: Researchers have tried for a long time to coax human muscle cells (obtained from needle biopsies) into contracting muscle fibers in a dish in order to be able to study human muscle physiology ex vivo. We are the first group that succeeded by carefully optimizing culture conditions including methods to expand and then culture cells in three-dimensional hydrogel matrices under passive tension. By doing so, we made first human muscle model that in response to electrical stimulation generates classical muscle contractile responses (twitch and tetanus). We have also shown that these engineered muscles (that we call "myobundles") contract in response to acetylcholine as it naturally happens when neurons in our body activate muscle. We demonstrated reproducibility and robustness of the approach by generating functional myobundles with similar properties from 10 independent donor muscle samples. We further went to show that myobundles have intact signaling characteristic of native muscle and respond to diverse set of drugs as human muscles do in clinics.
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MedicalResearch.com Interview with:
Anita Kohli MD
Critical Care Medicine Department
NIH Clinical Center, National Institutes of Health, Bethesda, MD
Clinical Research Directorate/Clinical Monitoring Research Program, Leidos Biomedical Research, National Laboratory for Cancer Research,
Frederick, MD,
Medical Research: What is the background for this study? What are the main findings?
Dr. Kohli: While therapy using for 8-12 weeks of all oral directly acting antivirals (DAAs) has been shown to result in high SVR "cure" rates for hepatitis C, the optimal combination and minimum duration required for treatment of hepatitis C has not been defined. The development of the simplest, short duration regimen for hepatitis C possible with high cure rates is important given the ~180 million people infected globally.
Medical Research: What should clinicians and patients take away from your report?Dr. Kohli: Combination therapy with directly acting antivirals may allow for the further shortening of treatment duration for hepatitis C. Using the right combination of DAA's therapy for as short as six-weeks may results in high rates of SVR.
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MedicalResearch.com Interview with:
Aymer Al-Mutairi, MD
Primary Care Research fellow
Dept. Family and Community Medicine
Baylor College of Medicine
Medical Research: What is the background for this study? What are the main findings?
Dr. Al-Mutairi: Previous studies indicate that 8% of abnormal imaging results did not receive follow-up actions by referring providers within 4 weeks. In addition, abnormal imaging results often state recommendations for further testing and radiology reports occasionally contain language that conveys doubt regarding the results.
We hypothesized that recommendations for further imaging, and expressions of doubt or uncertainty in the radiology report, are more likely to be associated with lack of timely follow-up. We found that patients with abnormal imaging results where radiologists recommended further imaging were less likely to be followed-up by a treating clinician within 4 weeks compared with patients without such recommendations. Expression of “doubt” in the radiology reports did not affect follow-up actions.
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MedicalResearch.com Interview with:
James Louis Januzzi, Jr, MD, FACC, FESC
Director, Cardiac Intensive Care Unit
Director, Dennis and Marilyn Barry Fellowship in...
MedicalResearch.com Interview with:
John N. Mafi, M.D.
Fellow, Harvard Combined Program in General Medicine
Beth Israel Deaconess Medical Center
Brookline, MA 02446
MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Mafi: Headache costs our healthcare system over 30 billion dollars annually. Clinical guidelines recommend conservative treatments for uncomplicated headache, such as counseling on dietary trigger avoidance. The Choosing Wisely Campaign of the American Board of Internal Medicine has in turn identified advanced imaging (e.g. CT or MRI) and opioid or barbiturate medications as low value treatments in the management of headache. In this context we used a nationally representative database to evaluate trends in physician practice patterns on headache management. We found a doubling in use of advanced imaging, referrals to other physicians and no change in opioid/barbiturate medications, although these continued to be used at high rates (18%). We also found a decline in life-style modification counseling, meant to prevent headaches from starting.
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MedicalResearch.com Interview with:
David L. Katz, MD MPH FACPM FACP
President of the American College of Lifestyle MedicineYale University Prevention Research Center
Derby, CT; Griffin Hospital, Derby, CT
Medical Research: What is the background for this study? What are the main findings?
Dr. Katz: We have long advised patients at risk for heart disease to avoid eggs- but have thought relatively little about what they might wind up eating instead. While coronary care units banish eggs, they routinely serve white bread, bagels, pancakes, etc. In general, the exclusion of eggs from the diet may result in more sugary, starchy foods- and if so, might do net harm. We have previously studied egg intake in healthy and dyslipidemic adults, and seen no adverse effects on blood flow or biomarkers in the short term (6 wks). This study examined this issue in adults with coronary artery disease- and again, no adverse effects were seen.
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MedicalResearch.com Interview with:
Eva Schernhammer, MD, DrPH
Associate Professor of Medicine
Brigham and Women's Hospital and Harvard Medical School
Associate Professor of Epidemiology
Harvard School of Public Health
Channing Division of Network MedicineMedical Research: What is the background for this study? What are the main findings?
Prof. Schernhammer: The study is an observational cohort study of over 70,000 registered nurses from within the US who reported the total number of years they had worked rotating night work and were followed for several decades. We examined overall mortality in these women, and observed significantly higher overall mortality, as well as higher mortality from cardiovascular disease in women with several years of rotating night shift work, compared to nurses who had never worked night shifts. There was also some suggestion for modest and non-significant increases in mortality from a few cancers. The study is unique due to its size, the fact that all participants were nurses (eliminating potential biases arising from differing occupational exposures), the long follow-up, and the possibility to take into account most known risk factors for chronic diseases that we currently know of (all of this information has been collected regularly and repeatedly). (more…)
MedicalResearch.com Interview with:
Inmaculada Hernandez, PharmD
PhD Student, Health Services Research and Policy
Deparment of Health Policy and Management
Graduate School of Public Health
University of Pittsburgh Pittsburgh, PA 15261
Medical Research: What is the background for this study? What are the main findings?Response: The approval of dabigatran was considered a major contribution to the therapeutic arsenal of anticoagulants since warfarin, whose therapeutic management is complicated, was the only oral anticoagulant approved before 2011. Clinicians therefore considered dabigatran a very promising drug; however, the safety warnings released by the regulatory agencies and the reports of bleeding published in 2011 raised concerns about the safety profile of dabigatran. By the time we initiated our study, the FDA had concluded that dabigatran was associated with similar rates of bleeding than warfarin. However, the results of this observational study were not adjusted by patient characteristics. We therefore compared the risks of bleeding with dabigatran and warfarin adjusting for patient characteristics and using propensity score methods to mitigate selection biases, which observational studies are sensitive to.
We found that dabigatran was associated with a higher risk of major bleeding and gastrointestinal bleeding than warfarin. However, the risk of intracranial bleeding was lower with dabigatran. In addition, we found that the increased risk of bleeding with dabigatran was specially higher for African Americans and for patients with chronic kidney disease.
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MedicalResearch.com Interview with:
Dr. Brent David MD
Academic Chief, Child and Adolescent Psychiatry at Western Psychiatric Institute and Clinic Professor of Psychiatry, Pediatrics & Epidemiology
University of Pittsburgh School of MedicineMedical Research: What is the background for this study?
Dr. David: There are now many studies that show that suicide and suicidal behavior run in families. A family history of suicide increases the risk for suicide attempt and vice versa, so that we believe that the trait that is being passed from parent to child is a tendency to act on suicidal thoughts, resulting in either an attempt or an actual suicide. However, what was not not known was the mechanism by which parents transmitted the risk of suicidal behavior to their children, and what the precursors of suicidal behavior looked like in individuals who were at risk for suicidal behavior, but had not yet engaged in a suicide attempt. Therefore, we conducted a high-risk family study, in which studied the children of parents with mood disorders, about half of whom also had a history of a suicide attempt.
Medical Research: What are the main findings?Dr. David: We followed 701 offspring for an average of 5.6 years, and found that those offspring whose parents had made a suicide attempt were almost 5 times more likely to make a suicide attempt themselves, even after accounting for mood disorder in parent and child and past suicidal behavior in the offspring. We found three main pathways by which suicidal behavior was passed from parent to child:
Parental mood disorder was transmitted to children, and that was a precursor of a suicide attempt.
Parent attempt was related to offspring impulsive aggression, which in turn increased the risk for mood disorder, which then increased the likelihood of a suicide attempt. (We define impulsive aggression as a tendency to response with hostility or aggression to provocation or frustration.
Finally, there is a direct path from parent attempt to child attempt, with no precursors or intervening variables.
Implications for clinicians and patients:
First, these findings highlight that a parental history of a suicide attempt increases the risk of an attempt in the parent's children. Clinicians who take care of adults who have attempted suicide should make sure that children are assessed as they are at increased risk and that parents know what to look for in the future in order to get their children into needed treatment.
Second, the transmission of suicidal behavior from parent to child can be attenuated by preventing the transmission of mood disorder, and of impulsive aggression. There are now evidence based interventions that reduce the likelihood of a child of a depressed parent from developing depression; these treatment involve cognitive behavioral principles and may also involve family interventions. There are now good family-based interventions for impulsive aggression that can attenuate the risk that the child or adolescent will go on to develop a mood disorder, which in turn greatly increases the risk for suicidal behavior.
MedicalResearch.com Interview with:
Yvonne Wu MD
Professor of Clinical Neurology and Pediatrics
UCSF School of Medicine
Medical Research: What is the background for this study? What are the main findings?Dr. Wu: Newborn infants commonly have elevated bilirubin levels, manifested as jaundice, because the body's mechanisms for breaking down bilirubin have not yet fully matured. Although high bilirubin levels are almost always well tolerated, extremely high bilirubin levels may lead to brain injury, or kernicterus, which in turn can cause a very severe form of cerebral palsy. When bilirubin levels are extremely high, or when bilirubin levels remain high despite phototherapy, it is recommended that an exchange transfusion be performed to prevent brain injury and cerebral palsy. The American Academy of Pediatrics (AAP) has published recommendations on when an exchange transfusion should be performed, based on bilirubin level, age of infant and other clinical factors. However, no previous study had examined the actual risk of cerebral palsy in infants whose bilirubin levels exceeded the exchange transfusion thresholds.
Among 500,000 newborns born at Kaiser Permanente Northern California over a 17-year period, we found 1833 who had at least one bilirubin level above the AAP exchange transfusion level. There were only 3 cases of cerebral palsy due to kernicterus in this group, even though only 42 (2.3%) of them had received exchange transfusions. All 3 infants had bilirubin levels at least 5 mg/dL above the AAP exchange transfusion threshold and all 3 infants had 2 or more other risk factors for brain damage, including prematurity, sepsis, hypoxia and the hereditary blood disorder G6PD deficiency. We did not identify any cases of kernicterus among otherwise well term babies, even at bilirubin levels that exceeded the AAP exchange transfusion threshold.
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MedicalResearch.com Interview with:
Dr. Georges Naasan MD
Neurologist, Clinical Instructor
UCSF Memory and Aging Center
Medical Research: What is the background for this study? What are the main findings?Dr. Naasan: Degenerative diseases of the brain can lead to dysfunction in judgment, emotional processing, social decorum and self-awareness. In turn, such dysfunctions may result in criminal behavior that appears for the first time in middle-aged adults or even later in life. We studied 2397 patients from the Memory and Aging Center at UCSF and found 204 (8.5%) that had a criminal behavior as part of their illness. The large majority of these patients were patients with a specific type of neurodegenerative disease called behavioral variant of frontotemporal dementia, followed by a group of people with a disease called semantic variant of primary progressive aphasia. People with Alzheimer's disease, a disease that does not usually interrupt the functions mentioned above, were the least likely to exhibit criminal behavior. The common manifestation of criminal behaviors in people with the behavioral variant frontotemporal dementia included theft, sexual advances trespassing and public urination in contrast to people with Alzheimer's disease who, when such behaviors were present, primarily committed traffic violations often secondary to cognitive impairment.
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MedicalResearch.com Interview with:
Alison G Abraham PhD
Associate Scientist
Department of Epidemiology
Johns Hopkins Bloomberg School of Public Health
Medical Research: What was the motivation for this study?Dr. Abraham: HIV-infected individuals are at higher risk for kidney dysfunction compared to the general population. Prior to effective antiretroviral therapy, very aggressive forms of kidney disease were described primarily among black HIV-infected individuals. While effective therapy and increasing viral suppression rates have made HIV-associated nephropathy rare, some of these same drugs have nephrotoxic effects. In addition, the reduction in AIDS and mortality has led to HIV-infected individuals living long enough to experience age-related chronic diseases, which are also risk factors for kidney disease and end-stage renal disease. Thus we wanted to know how these competing forces were affecting end-stage renal disease risk in the well-treated HIV-infected North American population over time. Are we seeing more ESRD as a result of nephrotoxic drugs and chronic disease, or less ESRD as a result of better viral suppression and large reductions in HIV-associated nephropathy?
Medical Research: What are the main findings?Dr. Abraham: We found that end stage renal disease rates have been steadily falling over the past 10 years coincident with notable improvements in viral suppression prevalence. However a large racial discrepancy in ESRD risk has persisted even though HIV-associated nephropathy cases are now rare. While ESRD cases among blacks in our study tended to have higher viral loads and lower CD4 counts compared to non-black ESRD cases, suggesting less effective HIV treatment, we found that the racial discrepancy in ESRD risk persisted even among the well-suppressed subset, i.e. those who had undetectable viral loads for 90% of their follow-up time.
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MedicalResearch.com Interview with:Qi Sun, MD ScDAssistant Professor of Medicine
Channing Division of Network Medicine
Brigham and Women’s Hospital and Harvard Medical School, Assistant Professor, Department of Nutrition
Harvard School of Public Health Boston, MA 02115Medical Research: What is the background for this study? What are the main findings?
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%.
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MedicalResearch.com Interview with:
Michael A. Weiss, MD, PhD
The Cowan-Blum Professor and Chairman of the Department of Biochemistry Distinguished Research Professor and Professor of Medicine in the Endocrine Division at the Case Western Reserve School of Medicine in Cleveland, Ohio.
Joseph Racca
Researcher and graduate student
Department of Biochemistry
Case 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 (Swyer’s 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.
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MedicalResearch.com Interview with:
Dr. Lynn C. Hartmann MD
Professor of Oncology, Mayo Clinic
Associate Director for Education of the Mayo Clinic Cancer Center.
Medical Research: What is the background for this study? What are the main findings?
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. (more…)
MedicalResearch.com Interview with:
Dr. Puneeth Iyengar, MD, PhD.Assistant Professor Director of Clinical Research
Dept of Radiation Oncology Co-leader, Thoracic Disease Oriented Team Harold Simmons Cancer Center
UT Southwestern Medical Center Dallas, TX
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.
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MedicalResearch.com Interview with:
Seth A. Berkowitz, MD, MPH
Division of General Internal Medicine
Massachusetts General Hospital, Boston Medical Research: What is the background for this study? What are the main findings?
Dr. Berkowitz: Prior studies had looked the association between single unmet basic material needs and diabetes control, but hadn't 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 (more…)
MedicalResearch.com Interview with:
Diederik Dippel MD, PhD
Senior Consultant in Neurology
Erasmus MC University Medical Center
Rotterdam The Netherlands
Medical Research: What is the background for this study? What are the main findings?
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.
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. (more…)
MedicalResearch.com Interview with:
Karthik Murugiah MBBS
Fellow in Cardiovascular Medicine
Yale School of Medicine
Center for Outcomes Research and Evaluation (CORE)
New Haven, CT 06510
Medical Research: What is the background for this study? What are the main findings?
Response: Aortic valve disease is common among older people and frequently requires valve replacement. 1-year survival after open surgical aortic valve replacement is high (9 in 10 survive the year after surgery). Our study focuses on the experience of these survivors in terms of the need for hospitalization during the year after surgery.
Among patients >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).
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MedicalResearch.com Interview with:
Dr. Annie Samraj MD
Postdoc Fellow
Varki Lab andAjit Varki MDDistinguished Professor of Medicineand Cellular & Molecular Medicine , Co-Director, Center for Academic Research and Training in Anthropogeny, Co-Director, Glycobiology Research and Training Center
University of California, San Diego, La Jolla, CA
Medical Research: What is the background for this study? What are the main findings?
Dr. Varki: For the past decade, there has been increasing evidence that people who consume red meat (beef, pork, lamb) are at a higher risk for certain kinds of cancers. Although red meat is a high quality source of protein, iron and vitamins, too much consumption may be harmful to humans. While there are other hypotheses under consideration, we focused on a non-human sugar molecule called Neu5Gc in red meat that could explain the link to cancer risk.
We extensively studied various foods and concluded that red meat (particularly beef) is rich in Neu5Gc. In contrast poultry, fish steaks and hen eggs have little or no Neu5Gc. From previous studies, we knew that animal-derived Neu5Gc could be incorporated into human tissues. In this study, we hypothesized that eating red meat could lead to inflammation if the body’s immune system targets the foreign Neu5Gc. Chronic inflammation is also known to instigate or promote tumor progression.
To test this hypothesis, we used mice engineered to be similar to humans in that they lacked Neu5Gc, and also produced antibodies against it. When these mice were fed Neu5Gc, they developed systemic inflammation. Tumor formation increased fivefold and Neu5Gc accumulated in the tumors, proving the hypothesis. None of the various control groups of mice showed this effect.
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MedicalResearch.com Interview with:
Jeffrey H. Silber, M.D., Ph.D.
The Nancy Abramson Wolfson Endowed Chair in Health Services Research Director, Center for Outcomes Research
The Children's Hospital of Philadelphia
Professor of Pediatrics, Anesthesiology & Critical Care
The Perelman School of Medicine
Professor of Health Care Management, The Wharton School
The University of Pennsylvania Philadelphia, PA 19104
Medical Research: What is the background for this study? What are the main findings?
Response: Differences in colon cancer survival by race is a well recognized problem among Medicare beneficiaries. We wanted to determine to what extent the racial disparity in survival is due to a racial disparity in presentation characteristics at diagnosis (such as advanced stage and the presence of chronic diseases) versus a disparity in subsequent treatment by surgeons and oncologists.
To answer this question, we compared black colon cancer patients to three matched white groups:
(1) “Demographics” match controlling age, sex, diagnosis year, and Survey, Epidemiology, and End Results (SEER) site;
(2) “Presentation” match controlling demographics plus comorbidities and tumor characteristics including stage and grade; and
(3) “Treatment” match including presentation variables plus details of surgery, radiation and chemotherapy.
We studied Medicare patients 65 years of age and older diagnosed between 1991-2005 in the SEER-Medicare database. There were 7,677 black patients and 3 sets of 7,677 matched white controls.
We found that difference in 5-year survival (black-white) was 9.9% in the demographics match. This disparity remained unchanged between 1991-2005. After matching on presentation characteristics, this difference fell to 4.9%. Finally, after additionally matching on treatment, this same difference hardly changed, moving to only 4.3%. So the disparity in survival attributed to treatment differences comprised only an absolute 0.6% of the overall 9.9% survival disparity.
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MedicalResearch.com Interview with:
Dr. Judy Karp, Dr. Antonio Wolff and Dr. Kala VisvanathanBreast Cancer Program
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, MD 21287
Medical Research: What is the background for this study? What are the main findings?
Response: The background for this study was the clinical observation from the Johns Hopkins Leukemia Program that a significant number of women with newly diagnosed acute myeloid leukemia had a personal history for breast and/or ovarian cancers. This observation led to our examination of the large NCCN breast cancer database in a multidisciplinary and multi-institutional study. The overarching finding in our study is that the risk of developing some form of leukemia following chemotherapy with or without radiation therapy, while small, continues to increase over at least 10 years without a plateau and is roughly twice what we thought it to be from previous breast cancer studies.
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MedicalResearch.com Interview with: Paul Schimmel, Ph.D. Professor
The Skaggs Institute for Chemical Biology,
The Scripps Laboratories for tRNA Synthetase Research
Department of Molecular and Cell Biology,
The Scripps Research Institute, La Jolla, CaliforniaMedical Research: What is the background for this study? What are the main findings?
Dr. Schimmel: Resveratrol (RSV) is thought to provide health benefits by activating a protective stress response. In the paper we described a new, previously missed mechanism for its action. This mechanism is activated at much lower concentrations of resveratrol than previously described or imagined. Consequently, other mechanisms, which appear to act at higher concentrations of resveratrol, are layered over a preexisting foundation set by the newly revealed mechanism.
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MedicalResearch.com Interview with:
Lee Zou, Ph.D.
Professor of Pathology, Harvard Medical School
The Jim & Ann Orr MGH Research Scholar
Associate Scientific Director, MGH Cancer Center
Medical Research: What is the background for this study? What are the main findings?
Dr. Lee Zou: Cancer cells must rely on telomerase or the alternative lengthening of telomere (ALT) pathway to maintain telomeres and bypass replicative senescence. The ALT pathway is active in about 10-15% of human cancers, and it is particularly prevalent in specific cancer types, such as osteosarcoma, glioblastoma, and neuroendocrine pancreatic tumors. ALT is a recombination-mediated process. Whether the reliance of cancer cells on alternative lengthening of telomere can be exploited therapeutically was not known.
In our study, we discovered that the ATR kinase is a key regulator of alternative lengthening of telomere. We found that ATR inhibitors disrupt ALT effectively. Furthermore, we found that ATR inhibitors selectively kill ALT-positive cancer cells in a panel of caner cell lines. These findings have suggested the first rational therapeutic strategy for the treatment of ALT-positive cancer. (more…)
