PSMA PET/CT Can Map Prostate Cancer Recurrences With Very Low PSA Levels

MedicalResearch.com Interview with:
Jeremie Calais PhD Ahmanson Translational Imaging Division UCLA Nuclear Medicine Department Los Angeles, CA 90095Jeremie Calais MD

Ahmanson Translational Imaging Division
UCLA Nuclear Medicine Department
Los Angeles, CA 90095

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

Response: The only curative treatment for recurrent prostate cancer after radical prostatectomy is salvage radiotherapy. Unfortunately, current standard imaging modalities are too insensitive to visualize the location of the recurrence until it is too late. As a result, salvage radiotherapy is directed to areas only suspected to harbor the recurrence based upon a “best guess” approach according to standard guidelines that define radiotherapy treatment volumes.

PSMA PET/CT is a new imaging technique with sensitivity sufficient to detect and localize the recurrent prostate cancer early enough to potentially guide salvage radiotherapy.

The first sign of prostate cancer recurrence is a rising PSA. For salvage radiotherapy to be successful, it should be initiated before the PSA rises above 1 ng/mL, and ideally, closer to 0.2 ng/mL or lower. PSMA PET/CT localizes sites of prostate cancer recurrence in up to 70% of patients with low PSA, below < 1.0.

In the US it is not yet FDA approved and currently only used for research purposes. In our current study we included 270 patients with early recurrence of prostate cancer after surgery from Germany and UCLA,  we found that 20 % of the patients had at least one lesion detected by  PSMA PET/CT which was NOT covered by the standard radiation fields. Obviously, salvage radiotherapy is only curative if recurrent disease is completely encompassed by the radiotherapy fields and would have failed in these patients.

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Carbon Monoxide Poisoning: Acute Brain Lesions on MRI Can Predict Delayed Sequelae

MedicalResearch.com Interview with:
“Danger Carbon Monoxide” by SmartSign is licensed under CC BY 2.0Won Young Kim, MD PhD
Department of Emergency Medicine
Asan Medical Center
University of Ulsan College of Medicine
Seoul, Korea

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

Response: Neurological symptoms of carbon monoxide (CO) poisoning can manifest not only immediately but also as late as 2 to 6 weeks after successful initial resuscitation as delayed neurological sequelae (DNS). To date, no reliable methods of assessing the probability of DNS after acute CO poisoning have been developed, which make it difficult to research the pathophysiology of DNS and targeting prevention.

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Brain Imaging Associated With Heritable Cognitive Ability and Psychopathology

MedicalResearch.com Interview with:
“The Fourth Sex: Adolescent Extremes” by Victor Soto is licensed under CC BY 2.0Dag Alnaes, PhD
Norwegian Centre for Mental Disorders Research
KG Jebsen Centre for Psychosis Research
Division of Mental Health and Addiction, Oslo University Hospital
Oslo, Norway 

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

Response: The transition from childhood to adulthood is characterized by swift and dramatic changes, both in our environment and in our brains. This period of life also coincides with the onset of many mental disorders.

To gain a better understanding of why, the clinical neurosciences must attempt to disentangle the complex and dynamic interactions between genes and the environment and how they shape our brains. The ultimate goal is to be able to predict which individuals are at risk before clinical symptoms appear. Advanced brain imaging has been proposed to represent one promising approach for such early detection, but there is currently no robust imaging marker that allows us to identify individuals at risk with any clinically relevant degree of certainty.

Our study shows that self-reported early signs of mental illness are associated with specific patterns of brain fiber pathways in young people, even if they may not fulfill criteria for a formal diagnosis or are currently in need of treatment.  Continue reading

FFRct Technology Can Eliminate Need For Coronary Angiogram In Some Patients

MedicalResearch.com Interview with:

MedicalResearch.com Interview with: Cardiologist Mark Rabbat, MD, FSCCT

Dr. Rabbat

Cardiologist Mark Rabbat, MD, FSCCT
Who pioneered the use of FFRct at Loyola Medicine and was first author of an international expert panel of leading cardiologists and radiologists from centers in the United States, Canada, Denmark, Italy, Belgium and the Netherlands on how to interpret and report the tests published in the Journal of Cardiovascular Computed Tomography 

MedicalResearch.com: What is the scope of the problem?

Response: Coronary artery disease is a very large healthcare burden. Over sixteen million individuals in the United States have coronary artery disease.  Coronary artery disease may result in your heart not getting enough blood and increases your risk of a heart attack.

Historically, we have been faced with either using tests we knew were not always accurate or putting a patient through an invasive angiogram just to determine whether they would need another invasive procedure to restore blood flow.  The CT-derived fractional flow reserve (FFRct) analysis is the first technology that bridges the gap between the non-invasive and invasive tests within one platform.  Any patient with symptoms such as chest pain, chest tightness, fatigue, or shortness of breath without known coronary artery disease may be a candidate for the FFRct study.  Continue reading

High Rates of Amyloid Imaging Positivity in Patients With Primary Progressive Aphasia

MedicalResearch.com Interview with:

Miguel A. Santos-Santos, MD Department of Neurology, Memory and Aging Center University of California San Francisco Autonomous University of Barcelona, Cerdanyola del Valles, Spain

Dr. Miguel A. Santos-Santos

Miguel ASantosSantosMD
Department of Neurology, Memory and Aging Center
University of California San Francisco
Autonomous University of Barcelona, Cerdanyola del Valles, Spain

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

Response: Primary progressive aphasia (PPA) is a clinically and pathologically heterogeneous (generally Frontotemporal lobar degeneration [FTLD, generally tau or tdp proteinopathies] or Alzheimer’s disease [AD] pathology) condition in which language impairment is the predominant cause of functional impairment during the initial phases of disease. Classification of PPA cases into clinical-anatomical phenotypes is of great importance because they are linked to different prevalence of underlying pathology and prediction of this pathology during life is of critical importance due to the proximity of molecule-specific therapies. The 2011 international consensus diagnostic criteria established a classification scheme for the three most common variants (the semantic [svPPA], non-fluent/agrammatic [nfvPPA], and logopenic [lvPPA]) of PPA and represent a collective effort to increase comparability between studies and improve the reliability of clinicopathologic correlations compared to the previous semantic dementia and progressive non-fluent aphasia criteria included in the 1998 consensus FTLD clinical diagnostic criteria. Since their publication, a few studies have reported amyloid imaging and pathological results in PPA, however most of these studies are retrospective in nature and the prevalence of FTLD and Alzheimer’s disease pathological findings or biomarkers in each variant has been inconsistent across the literature, therefore prospective validation with biomarker and autopsy data remains scarce and highly necessary.
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Sex Differences In Body Fat Composition Predictive of Cardiometabolic Risk Profile

MedicalResearch.com Interview with:

Miriam Bredella, MD Associate Professor of Radiology, Harvard Medical School Department of Radiology Massachusetts General Hospital Boston, MA 02114

Dr. Bredella

Miriam Bredella, MD
Associate Professor of Radiology
Harvard Medical School
Department of Radiology
Massachusetts General Hospital
Boston, MA 02114

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

Response: It is well known that body composition differs between men and women, with women having proportionally more fat and men more muscle mass.

But not the amount of fat but its distribution is an important determinant of cardiometabolic risk, with certain ectopic fat depots, such as visceral adipose tissue, fat within muscle cells – intramyocellular (IMCL), and liver fat, being more detrimental than others, such as femorogluteal subcutaneous adipose tissue.

We therefore wanted to study sex differences in body composition and cardiometabolic risk in men and women with obesity.

We found that at the same BMI, men had relatively higher visceral adipose tissue, IMCL, liver fat, muscle and lean mass, while women higher percent fat mass and higher subcutaneous adipose tissue. This female anthropometric phenotype was associated with a better cardiometabolic risk profile at similar BMI compared to men. However, ectopic fat depots were more strongly associated with adverse cardiometabolic risk factors in women compared to men

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Thunderclap Headache: Ottawa Rule To Exclude Subarachnoid Bleeding

MedicalResearch.com Interview with:

Jeff Perry, MD, MSc, CCFP-EM Professor, Department of Emergency Medicine Senior Scientist, Ottawa Hospital Research Institute Research Chair in Emergency Neurological Research, University of Ottawa Emergency Physician and Epidemiology Program The Ottawa Hospital Ottawa, Ontario

Dr. Perry

Jeff Perry, MD, MSc, CCFP-EM
Professor, Department of Emergency Medicine
Senior Scientist, Ottawa Hospital Research Institute
Research Chair in Emergency Neurological Research, University of Ottawa
Emergency Physician and Epidemiology Program
The Ottawa Hospital
Ottawa, Ontario

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

Response: Headache accounts for about 1-2% of all emergency department visits.  One of the most feared diagnosis within these patients is subarachnoid hemorrhage. While investigations are clearly warranted for patients with a diminished level of consciousness or new focal neurological deficits, approximately 50% of patients with subarachnoid hemorrhage (SAH) have no focal or global neurological findings. Deciding whether to image headache patients with no deficits is difficult, especially since timely diagnosis and treatment results in substantially better outcomes.

The desire to never miss a subarachnoid hemorrhage, however, contributes to escalating neuroimaging rates and a dogmatic adherence to lumbar puncture, even if the scan is negative, despite the very high sensitivity of computed tomography. However, a recent population-based study suggested that over 5% of confirmed subarachnoid hemorrhages were missed at initial presentation, especially in smaller hospitals. Therefore, identifying which headache patients require investigations to rule-out SAH is of great importance.

We have previously derived (N=1,999) and refined (N=2,131) the Ottawa SAH Rule. In this study, we conducted an multicenter prospective cohort study at six tertiary care hospitals, and found that the Ottawa SAH Rule performed well, with an 100% sensitivity, and specificity of 13.6%.

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FDG-PET Scans of Lung Nodules Should Be Interpreted With Caution

MedicalResearch.com Interview with:

PET Scan Vanderbilt Health

PET Scan Vanderbilt Health

Amelia W. Maiga, MD MPH
Vanderbilt General Surgery Resident
VA Quality Scholar, TVHS

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

Response: Positron emission tomography (PET) combined with fludeoxyglucose F18 (FDG) is currently recommended for the noninvasive diagnosis of lung nodules suspicious for lung cancer. Our investigation adds to growing evidence that FDG-PET scans should be interpreted with caution in the diagnosis of lung cancer. Misdiagnosis of lung lesions driven by FDG-PET avidity can lead to unnecessary tests and surgeries for patients, along with potentially additional complications and mortality.

To estimate FDG-PET diagnostic accuracy, we conducted a multi-center retrospective cohort study. The seven cohorts originating from Tennessee, Arizona, Massachusetts and Virginia together comprised 1188 nodules, 81 percent of which were malignant. Smaller nodules were missed by FDG-PET imaging. Surprisingly, negative PET scans were also not reliable indicators of the absence of disease, especially in patients with smaller nodules or who are known to have a high probability of lung cancer prior to the FDG-PET test.

Our study supports a previous meta-analyses that found FDG-PET to be less reliable in regions of the country where fungal lung diseases are endemic. The most common fungal lung diseases in the United States are histoplasmosis, coccidioidomycosis and blastomycosis. All three fungi reside in soils. Histoplasmosis and blastomycosis are common across much of the Mississippi, Ohio and Missouri river valleys and coccidioidomycosis is prevalent in the southwestern U.S. These infections generate inflamed nodules in the lungs (granulomas), which can be mistaken for cancerous lesions by imaging.

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Machine Learning Applied To Predicting High-Risk Breast Lesions May Reduce Unnecessary Surgeries

MedicalResearch.com Interview with:

Manisha Bahl, MD, MPH Director, Breast Imaging Fellowship Program, Massachusetts General Hospital Assistant Professor of Radiology, Harvard Medical School

Dr. Bahl

Manisha Bahl, MD, MPH
Director, Breast Imaging Fellowship Program,
Massachusetts General Hospital
Assistant Professor of Radiology,
Harvard Medical School

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

Response: Image-guided biopsies that we perform based on suspicious findings on mammography can yield one of three pathology results: cancer, high-risk, or benign. Most high-risk breast lesions are noncancerous, but surgical excision is typically recommended because some high-risk lesions can be upgraded to cancer at surgery. Currently, there are no imaging or other features that reliably allow us to distinguish between high-risk lesions that warrant surgery from those that can be safely followed, which has led to unnecessary surgery of high-risk lesions that are not associated with cancer.

We decided to apply machine learning algorithms to help us with this challenging clinical scenario: to distinguish between high-risk lesions that warrant surgery from those that can be safely followed. Machine learning allows us to incorporate the full spectrum of diverse and complex data that we have available, such as patient risk factors and imaging features, in order to predict which high-risk lesions are likely to be upgraded to cancer and, ultimately, to help our patients make more informed decisions about surgery versus surveillance.

We developed the machine learning model with almost 700 high-risk lesions, then tested it with more than 300 high-risk lesions. Instead of surgical excision of all high-risk lesions, if those categorized with the model to be at low risk for upgrade were surveilled and the remainder were excised, then 97.4% malignancies would have been diagnosed at surgery, and 30.6% of surgeries of benign lesions could have been avoided.

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Novel Brain Imaging May Detect Preclinical Alzheimer’s Disease

MedicalResearch.com Interview with:
Dr. Sanja Josef Golubic, dr. sc

Department of Physics, Faculty of Science
University of Zagreb, Croatia

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

Response: Our study was aimed to search the topological biomarker of Alzheimer’s disease. A recent evidences suggest that the decades long progression of brain degeneration that is irreversible by the stage of symptomatic Alzheimer’s disease, may account for failures to develop successful disease-modifying therapies. Currently, there is a pressing worldwide search for a marker of very early, possibly reversible, pathological changes related to Alzheimer’s disease in still cognitively intact individuals, that could provide a critical opportunity for evolving of efficient therapeutic interventions.

Three years ago we reported the discovery of the novel, fast brain pathway specialized for rapid processing of the simple tones. We named it gating loop. Gating loop directly links auditory brain areas to prefrontal brain area. We have also noticed the high sensitivity of the gating loop processing on AD pathology. It was inspiration to focus our Alzheimer’s disease biomarker search in the direction of prefrontal brain activation during listening of simple tones.

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Brain Imaging Patterns Moving Closer To Identifying Schizophrenia on Functional MRI

MedicalResearch.com Interview with:

Irina Rish PhD IBM T.J. Watson Research Center Yorktown Heights, NY 10598

Dr. Rish

Irina Rish PhD
IBM T.J. Watson Research Center
Yorktown Heights, NY 10598 

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

Response: Schizophrenia is a chronic and severe psychiatric disorder that affects roughly about 1% of population. Although it is not as common as other mental disorders, such as depression, anxiety, and attention deficit disorder (ADD), and so on, schizophrenia  is perhaps one of  the most debilitating psychiatric disorders,  preventing people from normal  functioning in daily life. It is characterized primarily by a range of psychotic symptoms, including hallucinations (false auditory, visual or tactile perceptions detached from reality), as well as delusions, disorganized thoughts, speech and behavior, and multiple other symptoms including difficulty showing (and recognizing) emotions, poor executive functioning, inattentiveness, problems with working memory,  and so one. Overall, schizophrenia has a devastating impact not only on patients and their families, but on the economy, as it was estimated to cost the US about 2% off  gross national product in treatment costs, missed work, etc.
Thus, taking steps towards better understanding of the disease can potentially lead to more accurate early diagnosis and better treatments.

In this work, the objective was to identify “statistical biomarkers’ of schizophrenia from brain imaging data (specifically, functional MRI), i.e. brain activity patterns that would be capable of accurately discriminating between schizophrenic patients and controls, and reproducible (stable) across multiple datasets. The focus on both predictive accuracy (generalization to previously unseen subjects) as well as on stability (reproducibility) across multiple datsets differentiates our work from majority of similar studies in neuroimaging field that tend to focus only on statistically significant differences between such patterns on a fixed dataset, and may not reliably generalize to new data.

Our prior work on neuroimaging-based analysis of schizoprenia http://journals.plos.org/plosone/article/related?id=10.1371/journal.pone.0050625, as well as other research in the field, suggest that disrupted functional connectivity can be a much more informative source of discriminative patterns than local changes in brain activations, since schizophrenia is well known to be a “network disease”, rather than a localized one.

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MRI Biomarkers Track Cognitive Impairment Due to Head Trauma

MedicalResearch.com Interview with:

Virendra Mishra, Ph.D. Department of Imaging Research Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas

Dr. Virendra Mishra

Virendra Mishra, Ph.D.
Department of Imaging Research
Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas

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

Response: Repetitive head trauma has been shown to be a risk factor for various neurodegenerative disorders, mood swings, depression and chronic traumatic encephalopathy. There has been a significant amount of research into identifying an imaging biomarker of mild traumatic brain injury (mTBI) due to repetitive head trauma. Unfortunately, most of the biomarkers have not been able to find a successful translation to clinics. Additionally, the quest for the mTBI imaging biomarker especially using Magnetic Resonance Imaging (MRI) techniques has been done by looking at either the gray matter (T1-weighted) or the white matter (Diffusion Tensor Imaging) independently; and both have shown changes that are associated with repetitive head trauma.

Hence in this study, we wanted to investigate if combining gray matter and white matter information enables us to better predict the fighters who are more vulnerable to cognitive decline due to repetitive head trauma. Our method found seven imaging biomarkers that when combined together in a multivariate sense were able to predict with greater than 73% accuracy those fighters who are vulnerable to cognitive decline both at baseline and follow-up. The imaging biomarkers were indeed a combination of gray and white matter measures of regions reported previously in the literature. A key point in our study was we found the regions predicting cognitive decline without enforcing any assumptions on the regions previously reported.

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Photodynamic Therapy Being Developed To Target Prostate Cancer

MedicalResearch.com Interview with:
Dr. Susanne Lütje
Ärztlicher Dienst
Universitätsklinikum Essen (AöR)
Klinik für Nuklearmedizin
Essen Germany

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

Response: Prostate cancer (PCa) is the most common cancer in men and accounts for a significant amount of morbidity and mortality. At present, the curative treatment option of choice for localized stages of PCa is radical prostatectomy, which may include extended lymph node dissection. Unfortunately, surgical procedures can be accompanied by complications such as urinary incontinence. Most importantly, small tumor deposits may not be seen by the surgeon during surgery and could ultimately lead to disease recurrence. To overcome these issues, new and innovative treatments are needed. The prostate-specific membrane antigen (PSMA) is a surface protein that is overexpressed in prostate cancer and can be used as a target to guide new therapies.

Photodynamic therapy (PDT) is an ablative procedure in which tumor cells can be destroyed effectively by irradiation of light of a specific wavelength, which activates previously administered photosensitizers. The photosensitizers can respond by emitting fluorescence or emitting oxygen radicals which can cause cellular damage. Coupling the photosensitizer to an agent that targets PSMA on the tumor surface offers the possibility to selectively and effectively destroy prostate tumor remnants and micrometastases, while surrounding healthy tissues remain unaffected.

In our study, the PSMA targeting antibody D2B was coupled to the photosensitizer IRDye700DX and radiolabeled with 111In. In a mouse model, this multi-modality agent was used to preoperatively visualize tumor lesions with SPECT/CT to allow rough localization of the tumors. During surgery, the fluorescent signal originating from the photosensitizer facilitates visualization of tumors and residual tumor tissue, so the surgeon can be guided towards accurate resection of the entire tumors and metastases. In addition, the PSMA-targeted PDT can be applied to destroy small tumor deposits in cases where close proximity of the tumors.

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MRI At Six Months Can Predict Which High Risk Babies Will Develop Autism

MedicalResearch.com Interview with:

Joseph Piven, MD The Thomas E. Castelloe Distinguished Professor of Psychiatry UNC School of Medicine Director of the Carolina Institute for Developmental Disabilities Co-senior author of the study

Dr. Piven

Joseph Piven, MD
The Thomas E. Castelloe Distinguished Professor of Psychiatry
UNC School of Medicine
Director of the Carolina Institute for Developmental Disabilities
Co-senior author of the study

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

Response: Babies with older siblings with autism are at an increased risk (20%) of getting autism over the general population (1%).  Infants who later are diagnosed with autism don’t have any of the stigmata of autism in the first year of life. The symptoms of autism unfold in the first and particularly in the second year of life and beyond.

We have evidence to support the idea that behavioral symptoms of autism arise from changes in the brain that occur very early in life. So we have employed MRI and computer analyses to study those early brain changes and abnormalities in infancy to see if early brain changes at 6 months of age can predict whether babies at high-risk of developing autism will indeed develop the condition at age two.

For this particular study, we used data from MRIs of six-month olds to show the pattern of synchronization or connection across brain regions throughout the brain and then predict which babies at high familial risk of developing autism would be most likely to be diagnosed with the condition at age two.

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Diagnostic Accuracy of FFR-CT Varies Across Spectrum of Coronary Artery Disease

MedicalResearch.com Interview with:
Dr Christopher Michael Cook MBBS Bsc(Hons) MRCP

MRC Clinical Research Fellow
NHLI, Cardiovascular Medicine, Imperial College London 

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

Response: FFR-CT is a novel non-invasive technique for estimating the functional significance of a coronary stenosis from CT coronary angiography images. A number of meta-analyses already exist for determining the diagnostic accuracy of FFR-CT (compared to invasive FFR as the reference standard). However, although knowing the overall diagnostic accuracy of FFR-CT is reassuring, in clinical practice a clinician knows not only whether the FFR-CT is positive or negative, but also its actual value. The purpose of this study was to provide clinicians a means of interpreting the diagnostic accuracy of any individual FFR-CT result that may be received in clinical practice.

MedicalResearch.com: What are the main findings?

Response: The main finding of this study is that the diagnostic accuracy of FFR-CT varies markedly across the spectrum of disease. For vessels with FFR-CT above 0.90, 98% met the invasive FFR guideline criterion for deferral. At the other end of the spectrum, for vessels with FFR-CT below 0.60, 86% met the invasive FFR guideline criterion for stenting. However, in between, FFR-CT gives less certainty as to whether the invasive FFR will meet the stenting criterion or not.

MedicalResearch.com: What should readers take away from your report?

Response: Readers can combine the findings of our study with patient specific factors in order to judge when the cost and risk of an invasive angiogram may safely be avoided. Because we now have a more complete picture of what different levels of FFR-CT mean in terms of invasive FFR, it is apparent that a single cut-off value for FFR-CT in deciding on invasive coronary angiography need not always apply. For example, in the asymptomatic patient, further investigations may not be desirable even if an FFR-CT still left a substantial possibility of a positive invasive FFR. Conversely, in the symptomatic patient, the patient and clinician would likely pursue invasive angiography unless the possibility of a positive FFR is very remote.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: This study adopted novel methodology to ascertain the probability that both FFR-CT and invasive FFR agreed on the functional classification of a stenosis, for any given individual FFR-CT value. This type of analysis could be used to determine if further iterative versions of the FFR-CT software translate into improved diagnostic performance, particularly in more intermediate disease severities. 

MedicalResearch.com: Is there anything else you would like to add?

Response:

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Cook CM, Petraco R, Shun-Shin MJ, Ahmad Y, Nijjer S, Al-Lamee R, Kikuta Y, Shiono Y, Mayet J, Francis DP, Sen S, Davies JE. Diagnostic Accuracy of Computed Tomography–Derived Fractional Flow Reserve A Systematic Review . JAMA Cardiol. Published online May 24, 2017. doi:10.1001/jamacardio.2017.1314

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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MRI Guided Prostate Biopsies Can Improve Care and Reduce Costs

MedicalResearch.com Interview with:

Vikas Gulani, MD, PhD Director, MRI, UH Cleveland Medical Center Associate Professor, Radiology, CWRU School of Medicine

Dr. Gulani

Vikas Gulani, MD, PhD
Director, MRI, UH Cleveland Medical Center
Associate Professor, Radiology, CWRU School of Medicine

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

Response: We wanted to learn if performing MR before prostate biopsy, followed by MR guided strategies for biopsy, are cost effective for the diagnosis of prostate cancer in men who have not previously undergone a biopsy and who have a suspicion of prostate cancer.

The most significant findings are as follows:

We found that all three MR guided strategies for lesion targeting (cognitive targeting, MR-ultrasound fusion targeting, and in-gantry targeting) are cost effective, as the increase in net health benefits as measured by addition of quality adjusted life years (QALY), outweigh the additional costs according to commonly accepted willingness to pay thresholds in the United States.

Cognitive targeting was the most cost effective. In-gantry biopsy added the most health benefit, and this additional benefit was cost-effective as well.

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No Magic Age To Stop Performing Screening Mammograms

MedicalResearch.com Interview with:
Cindy S. Lee, MD

Department of Radiology and Biomedical Imaging
University of California, San Francisco, San Francisco
Now with Department of Radiology
NYU Langone Medical Center, Garden City, New York

MedicalResearch.com: What led you and colleagues to conduct this study?

Response: I am a breast imager. I see patients who come in for their screening mammograms and I get asked, a lot, if patients aged 75 years and older should continue screening, because of their age. There is not enough evidence out there to determine how breast cancer screening benefits women older than 75. In fact, all previously randomized trials of screening mammography excluded people older than 75 years.

Unfortunately, age is the biggest risk factor for breast cancer, so as patients get older, they have higher risks of developing breast cancer. It is therefore important to know how well screening mammography works in these patients.

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Cardiac Magnetic Resonance Can Exclude Clinically Relevant Coronary Artery Disease

MedicalResearch.com Interview with:

Pr. Juerg Schwitter MD Médecin Chef Cardiologie Directeur du Centre de la RM Cardiaque du CHUV Centre Hospitalier Universitaire Vaudois - CHUV Suisse

Pr. Schwitter

Pr. Juerg Schwitter MD
Médecin Chef Cardiologie
Directeur du Centre de la RM Cardiaque du CHUV
Centre Hospitalier Universitaire Vaudois – CHUV
Suisse 

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

Response: Coronary artery disease (CAD) is still one of the leading causes of death in the industrialized world and as such, it is also an important cost driver in the health care systems of most countries. For the European Union, the estimated costs for CAD management were 60 billion Euros in 2009, of which approximately 20 billion Euros were attributed to direct health care costs (1). In 2015, the total costs of CAD management in the United States were estimated to be 47 billion dollars (2).

Substantial progress has been achieved regarding the treatment of CAD including drug treatment but also revascularizations procedures. There exists a large body of evidence demonstrating myocardial ischemia as one of the most important factors determining the patient’s prognosis and reduction of ischemia has been shown to improve outcome.

On the other hand, techniques to detect CAD, i.e. relevant myocardial ischemia, were insufficient in the past. Evaluation of myocardial perfusion by first-pass perfusion cardiac magnetic resonance (CMR) is now closing this gap (3) and CMR is recommended by most international guidelines for the work-up of known or suspected CAD (4,5).

Still, a major issue was not clarified until now, i.e. “how much ischemia is required to trigger revascularization procedures”. Thus, this large study was undertaken to assess at which level of ischemia burden, patients can be safely deferred from revascularization and can be managed by risk factor treatment only. Of note, this crucial question was addressed in both, patients with suspected CAD but also in patients with known (and sometimes already advanced) CAD, thereby answering this question in the setting of daily clinical practice.

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Doctors Continue To Order Mammograms Outside of Current Age Guidelines

MedicalResearch.com Interview with:
Archana Radhakrishnan MD MHS
Division of General Internal Medicine
Johns Hopkins University
Baltimore, Maryland

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

Response: We were interested in understanding the current practice trends in breast cancer screening recommendations by doctors in light of the guideline changes.  We performed a national survey of primary care providers and gynecologists asking about their breast cancer screening practices.

We found that a large number of doctors recommend breast cancer screening to younger and older women—upwards of 80% of doctors recommend it for younger women (ages 40-44) and almost 70% for women 75 and older.  But this varies by the type of doctor that a woman see.  Gynecologists were, in general, more likely to recommend routine mammograms.

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Ischemic Stroke: Collateral Blood Vessels Detected by Arterial Spin Labeling MRI Correlates With Good Neurological Outcome

MedicalResearch.com Interview with:
Jalal B. Andre M.D., D.A.B.R.®

Drector of neurological MRI and
MRI safety officer at Harborview Medical Center
University of Washington 

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

Response: Acute ischemic stroke (AIS) patients with good collaterals have better clinical outcomes. AIS is characterized by an ischemic penumbra, a region of salvageable brain tissue, that surrounds a core of irreversible ischemic infarct. The penumbra is tenuously perfused by collateral blood vessels which, if extensive enough, can maintain penumbral perfusion, improving the odds that a larger volume of brain tissue will survive. Standard, first-line methods for evaluating collaterals in the acute setting include CT angiography, MR angiography, and (less commonly) digital subtraction angiography. Arterial spin labeling (ASL) is an emerging MRI technique that assesses cerebral perfusion. Its advantages include relatively short scan time (4-6 minutes), lack of ionizing radiation, and independence from an exogenous contrast agent (contraindicated in patients with impaired renal function or documented sensitivity). Collaterals can be identified within ASL images as foci of curvilinear hyperintensity bordering regions of hypoperfusion. We sought to explore a novel relationship between the presence of ASL collaterals (ASLc) and neurological outcome in acute ischemic stroke patients.

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Instantaneous Wave-Free Ratio To Evaluate Coronary Artery Disease

MedicalResearch.com Interview with:

Matthias Götberg, MD, PhD Director Cardiac Cath Lab Department of Coronary Heart Disease Skane University Hospital- Lund Lund, Sweden

Dr. Matthias Götberg

Matthias Götberg, MD, PhD
Director Cardiac Cath Lab
Department of Coronary Heart Disease
Skane University Hospital- Lund
Lund, Sweden

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

Response: Cardiologists encounter patients with narrowing of the coronary arteries on a daily basis. They typically use visual estimation of the severity of narrowing when performing coronary angiography, but it is difficult to accurately assess, based on a visual estimation alone, whether a stent is needed to widen the artery and allow the blood to more freely.

FFR (Fractional Flow Reserve) is more precise tool and results in better outcomes than using angiography alone to assess narrowing of the coronary arteries. With FFR, the doctor threads a thin wire through the coronary artery and measures the loss of blood pressure across the narrowed area. To acquire an accurate measurement, the patient must be given adenosine, which is a drug that dilates the blood vessels during the procedure. This drug causes discomfort; patients describe having difficulty breathing or feeling as if someone is sitting on their chest. The drug also adds to the cost of the procedure and can have other rare but serious side effects.

iFR (Instantaneous Wave-Free Ratio) is also based on coronary blood pressure measurements using a thin wire, but unlike FFR, it uses a mathematical algorithm to measure the pressure in the coronary artery only when the heart is relaxed and the coronary blood flow is high. As a result, a vasodilator drug is not needed.
iFR has been validated in smaller trials and have been found to be equally good as FFR to detect ischemia, but larger randomized outcome trials are lacking.

iFR-Swedeheart is a Scandinavian Registry-based Randomized Clinical Trial (RRCT) in which 2000 patients were randomized between iFR and FFR as strategies for performing assessment of narrowed coronary vessels. The primary composite endpoint at 12 months was all-cause death, non-fatal myocardial infarction, and unplanned revascularization.
RRCT is a new trial design originating from Scandinavia using existing web-based national quality registries for online data entry, randomization and tracking of events. This allows for a very high inclusion rate and low costs to run clinical trials while ensuring robust data quality.

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iFR Can Assess Need For Coronary Revascularization Without Adenosine

MedicalResearch.com Interview with:

Dr. Justin Davies PhD Senior Reserch Fellow and Hononary Consultant Cardiologist National Heart and Lung Institute, Imperial College Londo

Dr. Davies

Dr. Justin Davies PhD
Senior Reserch Fellow and Hononary Consultant Cardiologist
National Heart and Lung Institute,
Imperial College London

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

Response: We know from the FAME study that compared to angiography alone, FFR guided revascularization improves long-term clinical outcomes for our patients. Despite this, adoption of FFR into everyday clinical practice remains stubbornly low. One major factor for this is the need for adenosine (or other potent vasodilator medications) in order to perform an FFR measurement. Adenosine is expensive, unpleasant for the patient, time consuming and even potentially harmful.

iFR is a newer coronary physiology index that does not require adenosine for its measurement. In the prospective, multi center, blinded DEFINE FLAIR study, 2492 patients were randomly assigned to either FFR guided revascularisation or iFR guided revascularization and followed up for a period of 1 year.
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Radiation Exposure and Vascular Access in Acute Coronary Syndromes: The RADMatrix Trial

MedicalResearch.com Interview with: Dr. Marco Valgimigli,

Dr. Marco Valgimigli

MedicalResearch.com Interview with:
Dr. Marco Valgimigli, MD, PhD

Interventional Cardiology
Sandro Pertini Hospital, ASL RM2, Rome, Italy

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

Response: Every year millions of people with coronary artery disease are treated worldwide with percutaneous coronary intervention (PCI). Radial access as compared to femoral access reduces bleeding and mortality in patients with acute coronary syndrome (ACS) undergoing invasive management. However, prior studies have raised concerns over the increased risk of radiation exposure for both patients and operators with radial instead of femoral access and it remains still unclear whether radial access increases the risk of operator or patient radiation exposure in contemporary practice when performed by expert operators.

The MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX) trial is the largest randomized trial comparing radial versus femoral access in ACS patients undergoing invasive management. In this radiation sub-study (RAD-MATRIX), we collected fluoroscopy time and dose area product (DAP) and equipped radial operators consenting to participate with dedicated dosimeters, each wearing a thorax (primary endpoint), wrist and head (secondary endpoints) lithium fluoride thermo luminescent dosimeter, during study conduct to establish non-inferiority of radial versus femoral access.

Among eighteen operators, performing 777 procedures in 767 patients, the non-inferiority primary endpoint was not achieved. Operator equivalent dose at the thorax was significantly higher with radial than femoral access. After normalization of operator radiation dose by fluoroscopy time or DAP, the difference remained significant. Radiation dose at wrist or head did not differ between radial and femoral access. Thorax operator dose did not differ in the right radial compared to the left radial access. In the overall MATRIX population, fluoroscopy time and DAP were higher with radial as compared to femoral access.

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Instantaneous Wave-free Ratio vs Fractional Flow Reserve to Guide PCI

MedicalResearch.com Interview with:

Dr. Matthias Götberg MD PhD Department of Cardiology, Clinical Sciences Lund University, Skåne University Hospital Lund, Sweden

Dr. Matthias Götberg

Dr. Matthias Götberg MD PhD
Department of Cardiology, Clinical Sciences
Lund University, Skåne University Hospital
Lund, Sweden

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

Response: Cardiologists encounter patients with narrowing of the coronary arteries on a daily basis. They typically use visual estimation of the severity of narrowing when performing coronary angiography, but it is difficult to accurately assess, based on a visual estimation alone, whether a stent is needed to widen the artery and allow the blood to more freely.

FFR (Fractional Flow Reserve) is more precise tool and results in better outcomes than using angiography alone to assess narrowing of the coronary arteries. With FFR, the doctor threads a thin wire through the coronary artery and measures the loss of blood pressure across the narrowed area. To acquire an accurate measurement, the patient must be given adenosine, which is a drug that dilates the blood vessels during the procedure. This drug causes discomfort; patients describe having difficulty breathing or feeling as if someone is sitting on their chest. The drug also adds to the cost of the procedure and can have other rare but serious side effects.

iFR (Instantaneous Wave-Free Ratio) is also based on coronary blood pressure measurements using a thin wire, but unlike FFR, it uses a mathematical algorithm to measure the pressure in the coronary artery only when the heart is relaxed and the coronary blood flow is high. As a result, a vasodilator drug is not needed.

iFR has been validated in smaller trials and have been found to be equally good as FFR to detect ischemia, but larger randomized outcome trials are lacking.

iFR-Swedeheart is a Scandinavian Registry-based Randomized Clinical Trial (RRCT) in which 2000 patients were randomized between iFR and FFR as strategies for performing assessment of narrowed coronary vessels. The primary composite endpoint at 12 months was all-cause death, non-fatal myocardial infarction, and unplanned revascularization.

RRCT is a new trial design originating from Scandinavia using existing web-based national quality registries for online data entry, randomization and tracking of events. This allows for a very high inclusion rate and low costs to run clinical trials while ensuring robust data quality.  Continue reading

Clinical Outcomes Following a Low-Suspicion MRI for Prostate Cancer

MedicalResearch.com Interview with:

Lars Boesen MD PhD Department of Urology Herlev Gentofte University Hospital Herlev

Dr. Boessen

Lars Boesen MD PhD
Department of Urology
Herlev Gentofte University Hospital
Herlev

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

Response: Transrectal ultrasound-guided biopsies (TRUS-bx) traditionally used for detecting prostate cancer (PCa) are prone to sampling errors due to difficulties in target identification. Therefore, concerns about the possibility of missing significant prostate cancer result in men with negative biopsy results frequently undergo repeated biopsies, leading to increased medical costs, patient anxiety and morbidity.

Multiparametric MRI (mp-MRI) has become increasingly important in prostate cancer diagnosis. A suspicious lesion can be targeted by MRI-guided biopsies and improve diagnosis. Conversely, a normal mp-MRI may non-invasively exclude the possibility of an aggressive disease, avoiding the need for further biopsies. However, there are no current guidelines for clinicians whether standard repeated biopsies (TRUS-bx) should be performed in men with either a low-suspicion mp-MRI or benign MRI-targeted biopsies of a suspicious lesion and the clinical outcome and future risk of detecting significant prostate cancer following these findings is unknown.

Therefore, we assessed the risk of being diagnosed with prostate cancer after either a low-suspicion mp-MRI or benign targeted biopsies of a suspicious lesion in men with prior negative TRUS-bx, but a persistent clinical suspicion of missed significant cancer over a follow-up period of at least three years. Our results suggest that a low-suspicion MRI in men with prior negative TRUS-bx can be used non-invasively in ruling out longer term significant cancer and immediate repeated biopsies are of limited clinical value and might be avoided even if prostate-specific-antigen levels are persistently elevated.

MedicalResearch.com: What should readers take away from your report?

Response: A low-suspicion mp-MRI in a man with prior negative TRUS-bx has a high accuracy in ruling out a significant aggressive prostate cancer during follow-up of at least three years. Thus, immediate repeated biopsies rarely find significant disease and could be avoided even if the prostate-specific-antigen level is persistently elevated.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Our results should be verified in larger prospective studies with a longer follow-up period to assess other clinical endpoints that include disease progression, cancer specific mortality and associated costs with an mp-MRI approach.

There are no disclosures or conflicts of interest

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Citation:
J Urol. 2017 Feb 21. pii: S0022-5347(17)30297-5. doi: 10.1016/j.juro.2017.02.073. [Epub ahead of print]
Clinical outcome following a low-suspicion multiparametric prostate MRI or benign MRI-guided biopsy to detect prostate cancer: A follow-up study in men with prior negative transrectal ultrasound-guided biopsies.
Boesen L1, Nørgaard N2, Løgager V3, Thomsen HS4.
Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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