Genetic Risk Score Predictive of Aggressive Prostate Cancer

MedicalResearch.com Interview with:
“DNA” by Caroline Davis2010 is licensed under CC BY 2.0Tyler Seibert, MD, PhD

Radiation Oncology
Center for Multimodal Imaging & Genetics
UC San Diego

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

Response: Prostate cancer is an extremely common condition in men. Many die from it each year, and many others live with debilitating pain caused by prostate cancer. Screening for prostate cancer with prostate-specific antigen (PSA) testing can be effective, but there are concerns with the test.

  • First, screening everyone gives a large proportion of false-positive results, and those men end up undergoing unnecessary procedures such as prostate biopsy. S
  • econd, a significant portion of men who develop prostate cancer will develop a slow-growing form of the disease that is likely not life-threatening and may not require treatment.

    These concerns have led to a drop in prostate cancer screening. But avoiding screening leaves a large number of men vulnerable to diagnosis of an aggressive prostate cancer at a later stage, when it is more difficult—or impossible—to be cured. Doctors are left to guess which of their patients are at risk of aggressive disease and at which age they need to start screening those patients.

Our study sought to develop a tool to provide men and their doctors with objective, personalized information about each man’s risk of prostate cancer. Based on the man’s genetics, we wanted to predict the risk of aggressive prostate cancer and at what age in his life that risk becomes elevated.

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PCOS: Hyperandrogenism Associated With Changes in Gut Microbiome

MedicalResearch.com Interview with:

Varykina Thackray, Ph.D. Associate Professor of Reproductive Medicine University of California, San Diego

Dr. Thackray

Varykina Thackray, Ph.D.
Associate Professor of Reproductive Medicine
University of California, San Diego

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

Response: Previous studies have shown that changes in the composition of intestinal microbes (gut microbiome) are associated with metabolic diseases. Since many women with polycystic ovary syndrome (PCOS) have metabolic dysregulation that increases the risk of developing type 2 diabetes and cardiovascular disease, we wondered whether PCOS was associated with changes in the gut microbiome and if these changes were linked to any clinical features of PCOS.

We collaborated with Beata Banaszewska and her colleagues at the Poznan University of Medical Sciences in Poznan, Poland to obtain clinical data and fecal samples from 163 premenopausal women recruited for the study. In collaboration with Scott Kelley at San Diego State University, we used 16S ribosomal RNA gene sequencing and bioinformatics analyses to show that the diversity of the gut microbiome was reduced in Polish women with PCOS compared to healthy women and women with polycystic ovaries but no other symptoms of PCOS.

The study confirmed findings reported in two other recent studies with smaller cohorts of Caucasian and Han Chinese women. Since many factors could affect the gut microbiome in women with PCOS, regression analysis was used to identify clinical hallmarks that correlated with changes in the gut microbiome. In contrast to body mass index or insulin resistance, hyperandrogenism was associated with changes in the gut microbiome in this cohort of women, suggesting that elevated testosterone may be an important factor in shaping the gut microbiome in women.

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Children with Heart Failure from Dilated Cardiomyopathy are Surviving Longer in the Most Recent Era

This file was derived from Blausen 0165 Cardiomyopathy Dilated.png

Structural categories of cardiomyopathy Wikipedia image

MedicalResearch.com Interview with:
Rakesh K. Singh MD, MS

Department of Pediatrics, University of California–San Diego and
Rady Children’s Hospital
San Diego, California

Steven E. Lipshultz MD
Department of Pediatrics
Wayne State University School of Medicine and
Children’s Hospital of Michigan
Detroit, Michigan 

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

Response: Dilated cardiomyopathy (DCM) is a disease characterized by dilation and dysfunction of the left ventricle of the heart. While DCM is a relatively rare disease in children, nearly 40% of children with DCM require a heart transplant or die within 2 years of diagnosis. Heart transplantation has improved the outcomes of children with DCM over the last 3 decades, but is limited by donor heart availability. Newer therapies, including advanced ICU care and artificial heart machines, are now being used to treat children with DCM.

This study published in the November 28, 2017 issue of the Journal of American College of Cardiology (JACC) sought to determine whether more children with DCM were surviving longer in the more recent era. Specifically, it investigated whether children with DCM were surviving longer without the need for heart transplantation. Rakesh Singh, MD is the first author and an Associate Professor of Pediatrics at UC San Diego/Rady Children’s Hospital, while the senior author is Steven Lipshultz, MD, Professor at Wayne State University School of Medicine/Detroit Medical Center’s Children’s Hospital of Michigan and Director of Children’s Research Center of Michigan.

The Pediatric Cardiomyopathy Registry (PCMR) is a National Heart, Lung, and Blood Institute (NHLBI) sponsored registry from 98 pediatric centers in United States and Canada created to study the outcomes of children with various heart muscle disorders known as cardiomyopathies. For this study, outcomes of 1,199 children diagnosed with DCM from 1990-1999 were compared with 754 children diagnosed with DCM from 2000-2009.

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Yoga May Reduce Disability and Opioid Use In Veterans With Chronic Low Back Pain

MedicalResearch.com Interview with:

Erik Groessl PhD Associate Adjunct Professor Family Medicine and Public Health University of California, San Diego

Dr. Groessl

Erik Groessl PhD
Associate Adjunct Professor
Family Medicine and Public Health
University of California, San Diego

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

Response: Chronic low back pain (cLBP) is prevalent among military veterans, but cLBP treatment options have limited benefits and side effects. This has resulted in efforts to reduce opioid use and embrace nonpharmacological pain treatments.

Yoga has been shown to improve health outcomes and have few side effects in non-veteran community samples.

Our objective was to study the effectiveness and safety of yoga for military veterans with chronic low back pain.  In a study of 150 veterans with cLBP, we found that yoga participants had greater reductions in disability and pain than those receiving usual. Opioid medication use declined among all participants, and no serious side effects occurred.

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Tofacitinib -XELJANZ: Potential New Treatment Option For Moderate To Severe Ulcerative Colitis

MedicalResearch.com Interview with:

William J. Sandborn, MD Professor of Medicine and Adjunct Professor of Surgery Chief, Division of Gastroenterology Vice Chair for Clinical Operations, Department of Medicine Director, UCSD IBD Center University of California San Diego and UC San Diego Health System

Dr. Sandborn

William J. Sandborn, MD
Professor of Medicine and Adjunct Professor of Surgery
Chief, Division of Gastroenterology
Vice Chair for Clinical Operations, Department of Medicine
Director, UCSD IBD Center
University of California San Diego and
UC San Diego Health System

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

Response: There is still a substantial unmet need for new treatments for patients with ulcerative colitis.

A previous Phase II study had suggested that tofacitinib might be effective for short term therapy of ulcerative colitis. The patients in that study for the most part had not failed anti-TNF therapy. Now we report the findings from 3 large Phase III trials, two short term trials and one long term trial, demonstrating that tofacitinib 10 mg twice daily is effective for short term therapy, and that both 5 mg and 10 mg twice daily is effective for long term therapy. We also demonstrated that tofacitinib is effective both in patients who have not failed anti-TNF therapy and patients who have failed anti-TNF therapy.

The study demonstrated induction of clinical remission, clinical response and mucosal healing (flexible sigmoidoscopy improvement) over the short term, and maintenance of clinical remission, clinical response, and mucosal healing over the long term.

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Gene “Decorations” Can Serve as Blood Biomarkers To Detect Cancer

MedicalResearch.com Interview with:

Kun Zhang, PhD Professor UCSD Department of Bioengineering La Jolla, CA 92093-0412

Dr. Kun Zhang

Kun Zhang, PhD
Professor
UCSD Department of Bioengineering
La Jolla, CA 92093-0412

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

Response: We have been interested in a type of chemical modification on the DNA, called CpG methylation, for years. This is like a decoration of DNA molecules that is specific to the cell type or tissue type. We were particularly interested in studying how such decoration spread along the DNA molecules. In this study, we did a very comprehensive search of the entire human genome for various human cell types and tissue types, and found close to 150,000 regions (called MHB in this study) in which adjacent CpG share the same decoration. We then went on to find out how many of such regions are unique to each normal cell/tissue type, and how many are specific to cancers. Then we took some of these highly informative regions as “biomarkers”, and showed that we can detect the absence or presence of cancer, and, in the latter case, where the tumor grow, in a patient’s blood.

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Schizophrenia: SynCav1 As Potential Target To Restore Neuron Function

MedicalResearch.com Interview with:

Brian P. Head, MS, PhD Associate Professor, UCSD Research Scientist, VASDHS Department of Anesthesiology VA San Diego Healthcare System San Diego, CA 92161-9125

Dr. Brian Head

Brian P. Head, MS, PhD
Associate Professor, UCSD
Research Scientist, VASDHS
Department of Anesthesiology
VA San Diego Healthcare System
San Diego, CA 92161-9125

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

Response: DISC1 is a schizophrenia associated gene originally identified in a Scottish family. DISC1 protein is highly expressed in the developing brain and in the dentate gyrus of the adult hippocampus, and is involved in neuritogenesis and neuronal signaling. DISC1 is located in multiple intracellular locations including axons and synapses, and loss of DISC1 function causes deficits in neural development, neuronal proliferation, axonal growth, and cytoskeleton modulation, which are consistent with abnormal neural development in schizophrenia.

SynCav1 means synapsin-driven caveolin construct. Synapsin promoter is neuronal specific which allows us to increase caveolin expression-specifically in neurons. We have previously shown that SynCav1 increases neuronal signaling and dendritic growth and arborization in vitro (Head BP JBC 2011), and when delivered in vivo augments functional neuroplasticity and improves learning and memory in adult and aged mice (Mandyam CD Biol Psych 2015).

Since loss of DISC1 function equates to schizophrenic-like symptoms, then decreased DISC1 expression in Cav-1 KO mice agrees with this premise. Thus, loss of Cav-1 increases their likelihood of developing schizophrenia-like symptoms. Because re-espression of Cav-1 restored DISC1 expression as well as expression of key synaptic proteins, this proof-of-concept findings not only builds upon our previously results demonstrating that Cav-1 is critical for neuronal signaling and functional synaptic plasticity but also strongly links Cav-1 with maintaining normal DISC1 expression levels and potentially attenuating schizophrenia-like symptoms.

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Many Atrial Fibrillation Patients At Risk of Stroke Receive Aspirin Instead of Appropriate Anticoagulation

MedicalResearch.com Interview with:

Jonathan Hsu, MD, MAS, FACC, FAHA, FHRS Assistant Professor Cardiac Electrophysiology, Division of Cardiology University of California, San Diego (UCSD)

Dr. Jonathan Hsu

Jonathan Hsu, MD, MAS, FACC, FAHA, FHRS
Assistant Professor
Cardiac Electrophysiology, Division of Cardiology
University of California, San Diego (UCSD)

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

Response: Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide and imparts significant stroke risk. In patients with AF determined to be at intermediate to high risk for thromboembolism, anticoagulation with warfarin (a vitamin K antagonist) or the newer non-vitamin K antagonist oral anticoagulants clearly reduces morbidity and mortality compared to aspirin. We sought to evaluate practice patterns of cardiovascular specialists in the United states to determine how often AF patients at risk for stroke are prescribed aspirin over oral anticoagulation, and predictors of this practice.

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JAMA Study Looks At Comparable Effectiveness of Four Weight Loss Medications

MedicalResearch.com Interview with:

Siddharth Singh, MD, MS Postdoctoral Fellow, NLM/NIH Clinical Informatics Fellowship Division of Biomedical Informatics Clinical Assistant Professor of Medicine, Division of Gastroenterology, Department of Internal Medicine, University of California San Diego, La Jolla

Dr Siddharth Singh

Siddharth Singh, MD, MS
Postdoctoral Fellow, NLM/NIH Clinical Informatics Fellowship
Division of Biomedical Informatics
Clinical Assistant Professor of Medicine, Division of Gastroenterology, Department of Internal Medicine,
University of California
San Diego, La Jolla

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

Dr. Singh: Over the last 4 years, four new medications have been approved for long-term use for weight loss by the FDA. We sought to evaluate the comparative effectiveness and tolerability of these medications through a systematic review and network meta-analysis. Based on 28 trials in over 29,000 overweight or obese patients, we observed that magnitude of weight loss achieved with these agents is variable, ranging from 2.6kg with orlistat to 8.8kg with phentermine-topiramate. Over 44-75% of patients are estimated to lose at least 5% body weight, and 20-54% may lose more than 10% of body weight; phentermine-topiramate was the most efficacious, whereas lorcaserin was the best tolerated.

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Biomarker Based Chemotherapy Approach Improved Outcomes

MedicalResearch.com Interview with:

Maria Schwaederle PharmD Clinical Research Scientist Center for Personalized Cancer Therapy UCSD Moores Cancer Center La Jolla, CA 92093

Dr. Maria Schwaederle

Maria Schwaederle PharmD
Clinical Research Scientist
Center for Personalized Cancer Therapy
UCSD Moores Cancer Center
La Jolla, CA 92093

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

Dr. Schwaederle: We performed this analysis with experts in the field, including but not limited to Drs Schilsky, Lee, Mendelsohn and Kurzrock, all known for their experience in the area of precision/personalized medicine.
Historically, phase I trials (which are often first in human or highly experimental in other ways) were believed to be examining only toxicity. Our meta-analysis of 13,203 patients shows that in the era of precision medicine, this historical belief needs to be discarded. Second, it is the use of precision medicine that makes this belief outdated.
Indeed, Phase I trials that utilized a biomarker-driven approach that is the essence of precision medicine had a median response rate of about 31%, which is higher than many FDA approved drugs, and this is in spite of the fact that phase I patients are a highly refractory group having failed multiple lines of conventional therapy.

Importantly, however, it was not the use of targeted agents alone that was important. It was the biomarker-based approach where patients are matched to drugs. Without matching, response rates were dismal—about 5%.

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