PAs Do More Biopsies, Find Less Early Melanoma than Dermatologists Interview with:

Laura Korb Ferris, MD, PhD Associate Professor, University of Pittsburgh Clinical and Translational Science Institute Director of Clinical Trials, Department of Dermatology University of Pittsburgh Medical Center

Dr. Laura K. Ferris

Laura K. Ferris MD, PhD
Associate Professor, University of Pittsburgh Clinical and Translational Science Institute
Director of Clinical Trials, UPMC Department of Dermatology
University of Pittsburgh What is the background for this study? What are the main findings? 

Response: Dermatology is one of the greatest utilizers of physician extenders, including physician assistants (PAs) in medicine. The scope of practice of PAs has also expanded over time from a role in assisting the dermatologist to taking a more independent role and many PAs now do skin cancer screening examinations and make independent decisions about which lesions are suspicious for skin cancer and need to be biopsied.

Our main findings were that, overall, in comparison to board-certified dermatologists, PAs were more likely to perform biopsies of benign lesions. For every melanoma that they found, PAs biopsied 39 benign lesions whereas dermatologists biopsied 25.

In addition, PAs were less likely than dermatologists to diagnose melanoma in situ, the earliest and most curable, but also hardest to identify and diagnose, form of melanoma. However, PAs had a similar rate of diagnosing the more clinically-obvious forms of skin cancer, including invasive melanoma, basal cell carcinoma, and squamous cell carcinoma.

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Erectile Dysfunction Drugs May Boost Effects of Chemotherapy Interview with:

Dr Pan Pantziarka

Dr Pan Pantziarka

Dr Pan Pantziarka, PhD
Program Director, Drug Repurposing: Anticancer Fund
Coordinator: Repurposing Drugs in Oncology
( What is the background for this study? What are the main findings?

Response: The Repurposing Drugs in Oncology (ReDO) project is an on-going collaboration assessing the evidence of anticancer activity in a wide range of already licensed non-cancer drugs. A subset of these drugs have a sufficient level of evidence to support clinical investigation and these are profiled in detail in order to synthesise the existing evidence and to bring it to the attention of clinical researchers.

In the case of the PDE5 inhibitors sildenafil, tadalafil and vardenafil the evidence is clear that these drugs have multiple anticancer mechanisms of action at clinically relevant dosing. In particular there is evidence that these drugs target anti-tumour immune responses, as shown from a small number of early stage clinical trials. This opens up the prospect of using these cheap and widely available drugs in combination with existing therapies to improve the number and duration of responses. The chance to increase the therapeutic effectiveness of immune checkpoint inhibitors is especially compelling and definitely warrants clinical research.

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Chemotherapy Choice Can Be Aided By Assessing TDP Profile Interview with:

Ed Liu, M.D President and CEO The Jackson Laboratory (JAX)

Dr. Ed Liu

Ed Liu, M.D
President and CEO
The Jackson Laboratory (JAX) What is the background for this study? What are the main findings?

Response: A few years ago we and others identified a complex genomic instability profile commonly found in the genomes of breast, ovarian and endometrial carcinomas, which is characterized by hundreds of isolated head-to-tail duplications of DNA segments, called tandem duplications. We refer to this configuration as the tandem duplicator phenotype, or TDP.

In this study, we perform a meta-analysis of over 2,700 cancer genomes from over 30 different tumor types and provide a detailed description of six different types of TDP, distinguished by the presence of tandem duplications of different sizes. Collectively, these profiles are found in ~50% of breast, ovarian and endometrial carcinomas as well as 10-30% of adrenocortical, esophageal, stomach and lung adeno-carcinomas. We show that distinct genetic abnormalities associate with the distinct TDPs, clearly suggesting that distinct molecular mechanisms are driving TDP formation. In particular, we provide strong evidence of a casual relationship between joint abrogation of the BRCA1 and TP53 tumor suppressor genes and the emergence of a short-span (~11 Kb) TDP profile. We also observe a significant association between hyper-activation of the CCNE1 pathway and TDP with medium-span (~230 Kb) tandem duplications, and between mutation of the CDK12 gene and medium- and large-span TDP (coexisting 230 Kb and 1.7 Kb tandem duplications).

Importantly, we find that different forms of TDP result in the perturbation of alternative sets of cancer genes, with short-span TDP profiles leading to the loss of tumor suppressor genes via double transections, and larger-span TDP profiles resulting in the duplication (i.e. copy number gain) of oncogenes and gene regulatory elements, such as super-enhancers and disease-associated SNPs.  Continue reading

Air Pollution Linked To Increased Respiratory Infections in Kids Interview with:

Benjamin D. Horne, PhD Director of Cardiovascular and Genetic Epidemiology Intermountain Heart Institute Intermountain Medical Center Salt Lake City, Utah 

Dr. Horne

Benjamin D. Horne, PhD
Director of Cardiovascular and Genetic Epidemiology
Intermountain Heart Institute
Intermountain Medical Center
Salt Lake City, Utah What is the background for this study?

Response: Evidence suggests that short-term elevations (even for just a few days) of fine particulate matter air pollution (PM2.5, which is particulate matter less than 2.5 um or about one-thirtieth the diameter of a human hair) is associated with various poor health outcomes among adults, including myocardial infarction, heart failure exacerbation, and worsening of chronic obstructive pulmonary disease symptoms. Studies of long-term exposure to moderately elevated levels of PM2.5 indicate that chronic daily air pollution exposure may contribute to death due to pneumonia and influenza.

Research regarding the association of short-term elevations in PM2.5 has provided some limited evidence of a possible association between short-term PM2.5 increases and infection with respiratory syncytial virus (RSV) or bronchiolitis in children, but scientifically these reports have been weak and unreliable, probably because they have only looked at a period of a few days to a week after short-term PM2.5 elevations. An evaluation of a very large population in a geographic location that provides a wide variation in PM2.5 levels from lowest to highest levels and that examines longer periods of time after the PM2.5 elevations is needed to determine whether a PM2.5 association with lower respiratory infection exists.

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Featured specializes in exclusive interviews with medical researchers from major and specialty journals and presenters at health care meetings.
Learn directly from the researchers as they discuss the ideas behind their investigations and their plans for future studies. Over 8844 interviews to date! More than 1766 interviews with researchers from JAMA, 312 Lancet, 301 NEJM, 394 TheBMJ interviews.

Patients With Highest LDL Levels Benefit Most From Lipid-Lowering Drugs Interview with:

Dr. Jennifer Robinson, MD MPH professor of epidemiology, University of Iowa College of Public Health. CREDIT Tom Langdon

Dr. Robinson

Dr. Jennifer Robinson, MD MPH
Professor, Departments of Epidemiology & Medicine
Director, Prevention Intervention Center
Department of Epidemiology
University of Iowa What is the background for this study?

Response: Compared to previous placebo-controlled statin trials, the FOURIER trial where all patients were on high or moderate intensity statin, had no reduction in cardiovascular or total mortality and the reduction in cardiovascular events was less than expected.  However, other PCSK9 inhibitor trials performed in populations with higher baseline low density lipoprotein cholesterol (LDL-C) had cardiovascular risk reductions similar to that in the statin trails.

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Risk of Cancer Triples Following Blood Clot in Leg Interview with:
Dr. Jens Sundbøll
Department of Clinical Epidemiology
Aarhus University Hospital
Aarhus, Denmark What is the background for this study? What are the main findings?

Response: The incidence of acute peripheral arterial occlusion is approximately 1.5 cases per 10,000 person-years. In comparison, the incidence rate of deep venous thrombosis is about 5-10cases per 10,000 person-years. It has been established previously that deep venous thrombosis in the lower limb and pulmonary embolism may be presenting symptoms of cancer and is associated with a poor cancer prognosis. However, whether arterial thromboembolism of the lower limb also can represent prodromal symptoms of occult cancer and worsen cancer prognosis has never been investigated.

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Blood Pressure Med Linked to Increased Risk of Pancreatic Cancer in Postmenopausal Women Interview with:

Zhensheng Wang, M.P.H., Ph.D. Postdoctoral Associate Duncan Cancer Center-Bondy Baylor College of Medicine Houston, TX, US

Dr. Wang

Zhensheng Wang, M.P.H., Ph.D.
Postdoctoral Associate
Duncan Cancer Center-Bondy
Baylor College of Medicine
Houston, TX What is the background for this study?

Response: Our prior research consistently found a significant inverse association between circulating levels of soluble receptor for advanced glycation end products (sRAGE), an anti-inflammatory factor, and risk of pancreatic cancer. It has also been found that sRAGE levels or RAGE signaling are modulated by anti-hypertensive (anti-HT) medications, including angiotensin-converting-enzyme inhibitors (ACEi), β-blockers, and calcium channel blockers (CCBs). These medications have been shown in prior pre-clinical or experimental research to either increase sRAGE concentrations, decrease formation of advanced glycation end-products (AGEs), or dampen pro-inflammatory receptor for AGE (RAGE) signaling pathway. We therefore hypothesized that there would be an inverse association between use of anti-HT medications and risk of developing pancreatic cancer.

Pancreatic cancer is a major public health concern in the United States, as it is the 4th leading cause of cancer-related mortality with an estimated of 43,090 deaths in 2017. Pancreatic cancer typically occurs in elderly individuals who also have chronic comorbid medical conditions, such as hypertension. Anti-HT medication use in individuals ≥ 18 years old has increased from 63.5% in 2001-2002 to 77.3% in 2009-2010, according to the National Health and Nutrition Examination Survey in the U.S. Therefore, it is of great public health significance to address the potential association between anti-HT medication use and risk of pancreatic cancer in the general population.

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Rhabdomyosarcoma Can Develop From Hijacked Blood Vessel Cells Interview with:

Mark E. Hatley, M.D., Ph.D. Assistant Member Molecular Oncology Division, Department of Oncology St. Jude Children's Research Hospital Memphis, TN 38105

Dr. Hatley

Mark E. Hatley, M.D., Ph.D.
Assistant Member
Molecular Oncology Division, Department of Oncology
St. Jude Children’s Research Hospital
Memphis, TN 38105 What is the background for this study? What are the main findings?

Response: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma occurring in children. Tumors appear histologically and genetically as undifferentiated skeletal muscle and are thus thought to solely originate from early skeletal muscle cells. However, tumors occur throughout the body, including sites devoid of skeletal muscle. In addition, tumor location is a key feature of staging and 40% of patients develop RMS in the head and neck. Interestingly, head and neck muscle development is distinct from the development of trunk and limb muscle. Previously we described a model of rhabdomyosarcoma which occurred specifically in the head and neck and originated from non-muscle cells. In this study we investigated how normal development programs are hijacked to drive rhabdomyosarcoma location.

We demonstrated that RMS can originate from immature blood vessel cells that lie in between muscle fibers specifically in the head and neck. During development, these cells are hijacked, and become reprogrammed into rhabdomyosarcoma rather than mature endothelial cells. These RMS cells express factors important in head and neck muscle development. Our findings highlight that cell of origin contributes to RMS location and may explain why a high proportion of RMS occurs in the head and neck.  Continue reading

Should Blood Pressure Measurement Be Repeated During Primary Care Visit? Interview with:
“Doctors” by Tele Jane is licensed under CC BY 2.0Doug Einstadter, MD, MPH

Center for Health Care Research and Policy
MetroHealth System and Case Western Reserve University What is the background for this study?  

Response: Despite the recognized importance of blood pressure (BP) control for those with hypertension, based on national surveys only 54% of patients with hypertension seen in primary care have their BP controlled to less than 140/90 mm Hg.

Blood pressure measurement error is a major cause of poor BP control. Reducing measurement error has the potential to avoid overtreatment, including side effects from medications which would be intensified or started due to a falsely elevated blood pressure. One way to reduce measurement error is to repeat the BP measurement during an office visit. The American Heart Association recommends repeating a blood pressure at the same clinic visit with at least 1 minute separating BP readings, but due to time constraints or lack of evidence for the value of repeat measurement, busy primary care practices often measure BP only once. Repeating the BP at the same office visit when the initial blood pressure measurement is high has the potential to improve clinical decision-making regarding BP treatment. Several studies have described the effect of a repeat BP measurement in the inpatient setting, but there are little data available to characterize the effect of repeating blood pressure measurement in an outpatient primary care setting.

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