Diabetes Drug May Enhance Melanoma Chemotherapy

MedicalResearch.com Interview with:

Bin Zheng, PhD Assistant Professor Cutaneous Biology Research Center Massachusetts General Hospital Harvard Medical School Charlestown, MA 02129

Dr. Bin Zheng

Bin Zheng, PhD
Assistant Professor
Cutaneous Biology Research Center
Massachusetts General Hospital
Harvard Medical School
Charlestown, MA 02129 

MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Melanoma is the most deadly form of skin cancer with more than 75,000 newly diagnosed cases in the US each year. Over the years, various genetic driver mutations have been identified that cause melanoma, including mutations in the genes BRAF and NRAS. Recent genetic insights into the development of melanoma showed that also mutations in NF1 can lead to melanoma. While there are targeted therapies available for BRAF-mutant melanoma, thus far no such therapies are available for NF1-mutant melanoma. We identified that using a combination of an ERK inhibitor, SCH772984, and the antidiabetic drug phenformin could provide a novel therapeutic strategy for NF1-mutatnt melanomas.

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Gene Therapy Restores Hearing Down To A Whisper, in Mice

MedicalResearch.com Interview with:

Gwenaelle Geleoc, PhD Assistant Professor Department of Otolaryngology F.M. Kirby Neurobiology Center Children's Hospital and Harvard Medical School Boston, MA

Dr. Gwenaelle Geleoc

Gwenaelle Geleoc, PhD
Assistant Professor
Department of Otolaryngology
F.M. Kirby Neurobiology Center
Children’s Hospital and Harvard Medical School
Boston, MA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We seek to develop gene therapy to restore auditory and balance function in a mouse model of Usher syndrome. Usher syndrome is a rare genetic disorder which causes deafness, progressive blindness and in some cases balance deficits. We used a novel viral vector developed by Luk Vandenberghe and package gene sequences encoding for Ush1c and applied it to young mice suffering from Usher syndrome. These mice mimic a mutation found in patients of Acadian descent. We assessed recovery of hearing and balance function in young adult mice which had received the treatment. Otherwise deaf and dizzy, we found that the treated mice had recovered hearing down to soft sounds equivalent to a whisper and normal balance function.

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Study Validates Good Quality Care Provided By Foreign-Trained Doctors

MedicalResearch.com Interview with:

Yusuke Tsugawa, MD, MPH, PhD Research Associate at Department of Health Policy and Management Harvard T.H. Chan School of Public Health

Dr. Yusuke Tsugawa

Yusuke Tsugawa, MD, MPH, PhD
Research Associate at Department of Health Policy and Management
Harvard T.H. Chan School of Public Health  

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Prior evidence has been mixed as to whether or not patient outcomes
differ between U.S. and foreign medical graduates.

However, previous studies used small sample sizes or data from a small number of states.
Therefore, it was largely unknown how international medical graduates
perform compared with US medical graduates.

To answer this question, we analyzed a nationally representative
sample of Medicare beneficiaries admitted to hospitals with a medical
condition in 2011-2014. Our sample included approximately 1.2 million
hospitalizations treated by 40,000 physicians. After adjusting for
severity of illness of patients and hospitals (we compared physicians
within the same hospital), we found that patient treated by
international medical graduates had lower mortality than patients
cared for by US medical graduates (adjusted 30-day mortality rate
11.2% vs 11.6%, p<0.001). We observed no difference in readmissions,
whereas costs of care was slightly higher for international medical
graduates.

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Intestinal and Blood-Brain Barrier Alterations Linked to Autism Spectrum Disorders

MedicalResearch.com Interview with:

Maria Rosaria Fiorentino, PhD

Dr. Maria Rosaria Fiorentino

Maria Rosaria Fiorentino, PhD
Assistant Professor at Harvard Medical School
Molecular Biologist at Mucosal Immunology and Biology Research Center
Massachusetts General Hospital East
Charlestown, MA 02129-4404

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Autism Spectrum Disorders (ASD) refers to complex neurodevelopmental disorders arising from the interaction of genes and environmental factors. There are no defined mechanisms explaining how environmental triggers can lead to these conditions. One hypothesis based on the gut-brain axis connection suggests that inappropriate antigens trafficking through an impaired intestinal barrier, followed by passage of these antigens through a permissive blood-brain barrier (BBB), can be part of the chain of events leading to the disease.

Many Autism Spectrum Disorders children experience co-morbid medical conditions, including gastrointestinal (GI) dysfunctions whose underlying nature is poorly understood. Several clinical observations describe increased intestinal permeability in ASD with often conflicting findings. Permeability to neuroactive food antigens derived from the partial digestion of wheat (gliadorphins) and cow’s milk (casomorphins) has been reported in ASD. However, while evidence of a permeable gut barrier in ASD is increasingly reported, no information is available concerning a similar breach for the BBB. The BBB is a critical line of defense in the Central Nervous System, limiting the access of circulating solutes, macromolecules, and cells that could negatively impact neuronal activity. Dysfunctions of the BBB have been associated with numerous inflammatory neurologic disorders, such as stroke, epilepsy, multiple sclerosis, Parkinson’s and Alzheimer’s disease.

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Physical Activity Linked to Improved Survival from Metastatic Colon Cancer

MedicalResearch.com Interview with:

Brendan John Guercio, M.D. Clinical Fellow in Medicine (EXT) Brigham and Women's Hospital

Dr. Brendan Guercio

Brendan John Guercio, M.D.
Clinical Fellow in Medicine (EXT)
Brigham and Women’s Hospital

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Sedentary lifestyle is a known risk factor for the development of colon cancer and has been associated with increased disease recurrence and mortality in patients with early stage colorectal cancer. This is the first study to our knowledge to show an association between increased physical activity (i.e. non-sedentary lifestyle) and improved survival and progression-free survival in patients with metastatic colorectal cancer.

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Migraine Increases Risk of Perioperative Stroke and Hospital Readmission

MedicalResearch.com Interview with:

Dr. Matthias Eikermann, MD, PhD Associate Professor of Anaesthesia, Harvard Medical School Clinical Director, Critical Care Division

Dr. Matthias Eikermann

Dr. Matthias Eikermann, MD, PhD
Associate Professor of Anaesthesia
Harvard Medical School
Clinical Director, Critical Care Division 

MedicalResearch.com: What is the background for this study?

Response: Up to one fifth of the general population have migraine, a primary, chronic-intermittent headache disorder affecting the neuronal and vascular systems and characterized by severe headache accompanied by nausea and/or sensory hypersensitivities such as photophobia and phonophobia. In approximately 20-30% of patients, the headache phase is preceded or accompanied by transient focal neurological disturbances presenting as visual symptoms but also sensory, aphasic, or motor symptoms known as migraine aura.

Stroke is responsible for approximately 6.2 million deaths a year and is a leading global cause of long term disability. Considering that more than 50 million patients in hospital and 53 million ambulatory patients undergo surgical procedures in the United States every year.

We found that patients with migraine, particularly migraine with aura, undergoing a surgical procedure are at increased risk of perioperative ischemic stroke and readmission to hospital within 30 days after discharge.

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PET Scanning Highlights Link Between Stress and Heart Disease

MedicalResearch.com Interview with:

Dr Ahmed Tawakol MD Massachusetts General Hospital and Harvard Medical Schoo

Dr Ahmed Tawakol

Dr Ahmed Tawakol MD
Co-Director, Cardiac MR PET CT Program
Massachusetts General Hospital and
Harvard Medical School 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: While the link between stress and heart disease has long been established, the mechanism mediating that risk hasn’t been clearly understood. Animal studies showed that stress activates bone marrow to produce white blood cells, leading to arterial inflammation.  This study suggests an analogous path exists in humans. Moreover, this study identifies, for the first time in animal models or humans, the region of the brain (the amygdala) that links stress to the risk of heart attack and stroke.

The paper reports on two complementary studies.

The first analyzed imaging and medical records data from almost 300 individuals who had PET/CT brain imaging, primarily for cancer screening, using a radiopharmaceutical called FDG that both measures the activity of areas within the brain and reflects inflammation within arteries.  All participants in that study had no active cancer or cardiovascular disease at the time of imaging and each had information in their medical records on at least three additional clinical visits after imaging.

The second study enrolled 13 individuals with a history of post-traumatic stress disorder, who were evaluated for their current levels of perceived stress and received FDG-PET scanning to measure both amygdala activity and arterial inflammation.

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Cangrelor With and Without Glycoprotein IIb/IIIa Inhibitors in Patients Undergoing PCI

MedicalResearch.com Interview with:

Deepak L. Bhatt, MD, MPH, FACC, FAHA, FSCAI, FESC Executive Director of Interventional Cardiovascular Programs, Brigham and Women’s Hospital Heart & Vascular Center Professor of Medicine, Harvard Medical School Boston, MA 02115

Dr. Deepak L. Bhatt

Deepak L. Bhatt, MD, MPH, FACC, FAHA, FSCAI, FESC
Executive Director of Interventional Cardiovascular Programs,
Brigham and Women’s Hospital Heart & Vascular Center
Professor of Medicine, Harvard Medical School
Boston, MA 02115

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Cangrelor is a potent, fast on, fast off, intravenous ADP receptor antagonist that is now available for use during PCI. Glycoprotein IIb/IIIa inhibitors are intravenous antiplatelet agents that work by a different mechanism. Doctors have asked whether there is any advantage to combining them or whether one class is preferable to the other during PCI.

We analyzed close to 25,000 patients from the CHAMPION trials. Cangrelor’s efficacy in reducing peri-procedural ischemic complications in patients undergoing PCI was present
irrespective of glycoprotein IIb/IIIa inhibitor administration. However, glycoprotein IIb/IIIa inhibitor use resulted in substantially higher bleeding rates, regardless of whether the patient was randomized to cangrelor or to clopidogrel.

Thus, in general, cangrelor and glycoprotein IIb/IIIa inhibitors should not routinely be combined. If an operator wishes to use a potent intravenous antiplatelet during PCI, cangrelor is similarly efficacious as glycoprotein IIb/IIIa inhibitors, but with less bleeding risk.

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New Microfluidic Technology Creates Microscale 3D Livers in a Droplet

MedicalResearch.com Interview with:

Prof. David A. Weitz Mallinckrodt Professor of Physics and Applied Physics School of Engineering and Applied Sciences Harvard University

Prof. David A. Weitz

Prof. David A. Weitz
Mallinckrodt Professor of Physics and Applied Physics
School of Engineering and Applied Sciences
Harvard University

MedicalResearch.com: What is the background for this technology study? What are the main findings?

Response: Currently, it is very time-consuming and expensive to develop new drugs. One reason is that many drugs fail in clinical trials after animal studies, simply because animals are very different from humans. One promising means of solving this problem is to replace animal experiments with artificial human tissues that can be used to directly screen a drug. However, it is a challenge to construct artificial human tissues, as almost all human tissues are composed of multiple types of cells and extracellular matrices in 3D structures.

In our studies, we have successfully developed a droplet-based microfluidic technique to fabricate large numbers of monodisperse, portable microtissues. We spatially assemble different types of cells in a 3D core-shell structure and construct an artificial human microtissue in each individual drop. The specific structures we create in the microdoplets are designed to mimic the behavior of the liver, and hence we call these structures a ‘liver in a drop.’  Continue reading

Patients Treated By Female Doctors Have Better Outcomes and Fewer Readmissions

MedicalResearch.com Interview with:

Yusuke Tsugawa, MD, MPH, PhD Department of Health Policy and Management Harvard T. H. Chan School of Public Health, Department of Medicine Brigham and Women’s Hospital and Harvard Medical School Boston, Massachusetts

Dr. Yusuke Tsugawa

Yusuke Tsugawa, MD, MPH, PhD
Department of Health Policy and Management
Harvard T. H. Chan School of Public Health,
Department of Medicine
Brigham and Women’s Hospital and Harvard Medical School
Boston, Massachusetts 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We analyzed a 20% sample of Medicare beneficiaries hospitalized with a medical condition in 2011-2014, and found that patients treated by female doctors have lower mortality and readmission rates than those cared for by male doctors.

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New Strategy for Malaria Control Uses Non-Toxic Steroid Agonists

MedicalResearch.com Interview with:

Dr-Flaminia-Catteruccia.jpg

Dr. Catteruccia

Flaminia Catteruccia PhD
Associate Professor of Immunology and Infectious Diseases
Department of Immunology and Infectious Diseases
Boston, Massachusetts 02115

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Mosquito control via lethal insecticides is a key method for reduction of malaria transmission. As insecticide resistance is spreading, new intervention methods are urgent. Our study demonstrates that studies on mosquito biology can provide novel, much needed tools for malaria control. We show how key aspects of mosquito physiology and Plasmodium development can be significantly disrupted in the female Anopheles mosquito by agonists of the insect steroid hormone 20-hydroxyecdysone (20E). Modeling of the data predicts that the integration of 20E agonists in malaria control programs would significantly reduce malaria prevalence to a similar extent as insecticides, but without imposing severe costs to mosquito populations

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