FDA APPROVED BLOOD TESTS TO DETECT CANCER

"FDA Approves Blood Tests That Can Help Guide Cancer Treatment" was originally published by the National Cancer Institute. |  October 15, 2020, by NCI Staff

Two blood tests recently approved by FDA for use in some people with cancer, known as liquid biopsies, identify genetic changes by scanning DNA that tumors have shed into the blood.  (image credit: ref: #1)

The Food and Drug Administration (FDA) has approved two blood tests, known as liquid biopsies, that can help guide treatment decisions for people with cancer. The tests, Guardant360 CDx and FoundationOne Liquid CDx, are made by different companies and were approved separately.

Doctors have traditionally based treatment decisions on features like the organ in which the cancer started growing, whether the cancer has spread, and whether the patient has other health conditions. Now they often use another feature to guide treatment: genetic changes in the tumor. 

Certain therapies, called targeted therapies and immunotherapies, work best against tumors that have specific genetic changes. The newly approved tests identify genetic changes, including mutations, by scanning DNA that tumors have shed into the blood. 

Doctors can then use that information to determine if there is a targeted therapy or immunotherapy that is likely to work for the patient. Analyzing genetic changes in a patient’s cancer is called tumor profiling, genomic profiling, or tumor sequencing.

Both Guardant360 CDx and FoundationOne Liquid CDx are approved for people with any solid cancer (e.g., lung, prostate), but not for those with blood cancers. While FDA has approved other blood tests that check for the presence a single gene mutation in tumor DNA, these are the first approved blood tests that check for multiple cancer-related genetic changes.

Liquid biopsies can sometimes be an alternative to a traditional biopsy, in which a sample of a tumor is removed with a needle or during surgery. They are considered less invasive and quicker than a traditional tissue biopsy. 

“Even though the tests have been around for a while, we don’t know how useful they’re really going to be in the clinical setting,” said Ben Ho Park, M.D., Ph.D., of Vanderbilt-Ingram Cancer Center. Many details about how the blood tests may be incorporated into everyday care for people with cancer, including who should get them and whether the cost is covered by private insurance companies, are still being ironed out.  What the FDA’s stamp of approval provides, Dr. Park explained, is validation that the results of a blood-based tumor profiling test can be used to guide the selection of a targeted therapy. 

“It’s great that we’ve crossed that hurdle now. It’s great for patients [because] it’s easier to get,” he said.

See complete article @ NIH (https://www.cancer.gov/news-events/cancer-currents-blog/2020/fda-guardant-360-foundation-one-cancer-liquid-biopsy)

GENETICS VS. GENOMICS By: Dr. Roberta Kline, MD  Genetics and genomics sound alike and are often used interchangeably, yet important scientific and clinical distinctions exist between these two scientific fields of study. The classical definition of genetics is the study of heredity, how characteristics and traits (phenotypes) of a living organism are transmitted from one generation to the next. This occurs via deoxyribonucleic acid (DNA), a double helix molecule in the cell’s nucleus that comprises genes—the basic unit of heredity. Many of the early principles and rules of heredity were discovered by an Augustinian monk and scientist, Gregor Mendel. His seminal research with pea plants in the mid-1800’s laid the foundation for modern-day genetics. Genomics is the next evolution of classical genetics, and became possible only in recent decades due significant advances in DNA sequencing and computational biology. In 1976, Belgian scientists succeeded in fully sequencing the genome of bacteriophage MS2, a bacteria-infecting virus. They identified all 3,569 DNA base pairs, and the 4 nucleotides (Adenosine, Cytosine, Guanine and Tyrosine) that make up the DNA code. The first animal genome was completely sequenced in 1998. Five years later, with more than 1,000 researchers from six countries collaborating on the Human Genome Project, all 3.2 billion DNA base pairs in the human genome were identified.  Genomics is the study of the entirety of an organism’s genes—the genome. Genomic researchers analyze enormous amounts of DNA-sequence data to find variations that affect health, disease or drug response. In humans, that means searching through about 3.2 billion units of DNA across 23,000 genes. See complete article: INHERITING CANCER- 12/5/2020

PSA Blood Test vs. Cancer Imaging?

By: Dr. Robert L. Bard

The strategy of relying on a (PSA) blood test as the precursor to a biopsy required significant reassessment.  Though approved by the FDA in 1986 as the gold standard for monitoring cancer relapses, increasing reports continue to indicate that elevated PSA levels in over 70% of men show a false positive reading- and does not conclude a malignant cancer. (NIH ref). Because of the inaccuracies of the PSA test and the risk of side effects, many centers are now using imaging solutions like ultrasound 3-D Doppler and MRI before considering a biopsy.

Patient-Specific Anxiety: "My PSA was 22. I had a biopsy; it was benign...GOOD! The biopsy showed inflammation, so I had a (surgical) biopsy I didn’t need... BAD!  There has to be a better way!” 

CANCER IMAGING:

The GenX Diagnostic Solution

Medical imaging (and screening) especially of cancer tumors has advanced since the establishment of the x-ray in 1895.  Imaging earned the acceptance in the medical community as a low-risk, reliable and non-invasive (no-cutting) alternative.  It is widely employed today as a routine and standardized diagnostic protocol in almost every area of healthcare.  Treatment specialists and research scientists alike rely (solely) on medical imaging technology as the go-to protocol to investigate a patient's physiological condition in pathology studies. 

The DIGITAL MOVEMENT and the "end of FILM in radiology" was part of the global tech evolution- driven by the "Economics of Scale theory of Faster-Better-Cheaper". The digital imaging revolution harvested and processed images from an electronic photo conductor, managed bio-information into electronic pixels for more efficient management of diagnostic studies.  The Digital state allowed for computerized intervention to optimize and expand the data acquiring process to new heights of study including 3D modeling- offering a 3D visualization of anatomical studies.  This also paved the way for the induction of AI (artificial intelligence) which was developed to automate analytical paradigms (algorithms) for quicker analysis, advanced workflow, optimized visual dissection, extrapolation and 'prediction' of any biological information with remarkable performance. (see complete article) 

References

1)  Image #1: (Credit: Adapted from World J Gastroenterol. October 2016. doi:10.3748/wjg.v22.i38.8480. CC BY-NC 4.0)

2) Complete article: NIH (https://www.cancer.gov/news-events/cancer-currents-blog/2020/fda-guardant-360-foundation-one-cancer-liquid-biopsy)

3) Circulating tumor DNA as a liquid biopsy target for detection of pancreatic cancer https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5064029/

VERIFYING SIGNS OF COVID-19 STROKE THROUGH IMAGING

 By: Robert L. Bard, MD  and Dr. Pierre Kory, MD

ABSTRACT 

Early detection and prevention of arterial and venous disease is key to minimizing the effects of arterial obstruction & hemorrhage,  brain aneurysms, and strokes from venous thrombosis.  The association of trauma to PTSD is now followed by advanced Doppler ultrasound and functional MRI. This abnormal physiology may also manifest as arterial dissection, collagen disease, inflammatory arthritis, dermatitis, ocular disorders, GI disturbances, limb pain, aneurysms of the brain and aorta. Devastating strokes in the Covid-19 era occur in the younger age group and the Latin population is at higher risk.

INTRODUCTION 

Interest in arteritis was elevated with the study of Tayakasu’s disease in the 1970s when advances in contrast arteriography diagnosed diffuse vascular involvement causing strokes and aneurysms in multiple sites. While this arterial inflammation is more common in Asians, in the US, blacks are nearly three times more likely to have a stroke at age 45 than whites. The pediatric population seems to be at higher risk for this arteritis as evidenced by their unusual rate of Covid-19 affliction affecting the vasculature and called “MULTIPLE ACUTE INFLAMMATORY SYNDROME“. Birth control pills is a distinct cause of such disease in younger women while cancer, alcoholism and obesity raise the incidence at all ages.

We have learned over the last century that blockages of coronary arteries to the heart and carotid arteries to the brain are precipitated by inflammation of the inner walls of the vessel, called the “intima”

While thickening of the interior wall of vessels gradually occurs over time and is aggravated by diet, stress and hypertension (high blood pressure), the acutely disabling event is when there is an abrupt tear of the overlying plaque which ruptures debris which then forms a blood clot which blocks blood flow or the clot travels deeper into the brain and blocks blood flow. Similarly, abnormal heart rhythms such as “atrial fibrillation”, causes the pooling of blood in the heart which predisposes to clot formation and the clots can then travel into the brain causing a stroke. In Covid-19, the virus causing severe inflammation in the blood which then promotes clot formation which can travel through the vascular system and affect  almost every organ system in the human body, with the brain and lungs being the most affected.. An article in September NEUROLOGY reported by Medscape documented the incidence of large artery stroke as the presenting symptom of  COVId-19 was highest in men under the age of 50 years. 

HISTORY

A medical research team at Metropolitan Hospital in New York first noticed unusual neurologic symptoms in young and middle aged patients in the late 1960s. As a division of the NY Medical College system, they were fortunate to have an active interventional radiology department specializing in neuroimaging and arteriography. The observation of distortion and occlusion of arteries supplying the brain, kidneys, GI tract and lower limbs to various degrees from single to multiple locations was closely linked to the Japanese disorder known as Tayakasu’s arteritis at the time and recently renamed “arteritis.” A clinical finding of this arterial inflammation in the abdominal aorta was pain in the upper abdomen by the great vessels by palpation. Astute physicians were successfully treating this with commonly available “aspirin.”

However, the chronic and diffuse nature of arteritis often weakened the vessel wall producing aneurysmal dilation and rupture. Today we find sophisticated non-invasive or minimally invasive modalities to be the first line of interrogation of vasculitis.

COVID AND STROKE

COVID-19 was rapidly understood as a disease caused by severe and widespread inflammation and “hypercoagulability” (a tendency to spontaneously form clots in the blood vessels. Autopsies have revealed extensive small vessel strokes, with such strokes often occurring despite aggressive blood thinner treatment and regardless of the timing of the disease course, suggesting that it plays a role very early in the disease process. In one autopsy series, there was a widespread presence of small clots with acute stroke observed in over 25%. In a recent review of the incidence of stroke in COVID-19, almost 2% of all hospital patients suffered a stroke, which is 8x higher than in patients with influenza. More worrisome is that this is almost definitely a gross underestimate given the many likely missed strokes in patients who died on ventilators who were too ill to obtain imaging, the general restrictions on and lack of autopsies, and the well-recognized decrease in the number of patients with acute stroke symptoms seeking medical attention in the COVID-19 era.  Another worrisome finding from a recent study of COVID-19 cases found that 45.5% of patients reported neurologic symptoms [4]. This under-recognized epidemic of neurological symptoms and strokes in COVId-19 highlights the need for more intensive imaging and investigation to achieve not only earlier recognition and improved treatment of patients but in furthering understanding of COVID-19 effects on brain function.

DIAGNOSIS BY IMAGING

Blood flow abnormalities in the arterial system are best study by Doppler imaging like the weather Doppler showing tornadoes. Multiple options exist for blood flow analysis including:

- CAROTID SONOGRAM - CAROTID DOPPLER - EYE SONOGRAPHY - TRANSORBITAL DOPPLER - CONTRAST ENHANCED ULTRASOUND - TRANSCRANIAL DOPPLER - HYBRID IMAGING

- 3D/4D VESSEL DENSITY HISTOGRAM - ENDOARTERIAL 3D DOPPLER - RETINAL OCT - SOFT TISSUE OCT - REFLECTANCE CONFOCAL MICROSCOPY - SMALL COIL MRI - 7 TESLA MRI

CAROTID SONOGRAM: While cerebrovascular disease is often diagnosed ex post facto after a catastrophic episode with MRI and CT, the non invasive Doppler analysis of the vascularity is generally checked with ultrasound for plaque and obstruction. A useful measure of the risk of coronary and cerebrovascular disorder is the carotid intimal thickness (CIMT). Standard depth of the inner wall thickness is a measure best obtained by high resolution sonograms since a reading over 0.9mm indicates increased risk. The newer sonogram units have depth resolution of 0.02mm making this a preferred non invasive option.

CAROTID DOPPLER: Flow abnormalities of turbulence and absence are commonly evaluated with this modality. Plaque forms more readily in aberrant flow patterns and high velocity regions accompanying narrowing.

EYE SONOGRAPHY: Sonofluoroscopy of the orbital soft tissues and eyes is performed in multiple scan planes with varying transducer configurations and frequencies. Power and color Doppler use angle 0 and PRF at 0.9 at optic nerve head. 3D imaging of optic nerve and carotid, central retinal arteries and superficial posterior ciliary arteries performed in erect position before and after verbal communication. Retinal arterial flow is measured. Optic nerve head bulging is checked as increased intracranial pressure may be demonstrable.

TRANSORBITAL DOPPLER: R/L ciliary arteries have normal Doppler flows of 10cm/s which is symmetric.

CONTRAST ENHANCED ULTRASOUND: Widely used European nonionic contrast injection allows imaging capillary size vessels and perfusion characteristics

TRANSCRANIAL DOPPLER: This measures the flow in the anterior, middle and posterior cerebral arteries as well as Circle of Willis.

3D/4D VESSEL DENSITY HISTOGRAM: Multiple image restoration and reconstruction shows retinal vessel density of 25% at the optic nerve head and adjacent region with quantitative accuracy.

ENDOARTERIAL 3D DOPPLER: Microcatheters inserted into the arterial or venous system provide measurement of wall thickness and presence of inflammatory vessels inside the intima.

RETINAL OCT: Subtraction techniques done with OCT optical coherence tomography may show changes in the caliber of the retinal vessels with verbal ideation.

SOFT TISSUE OCT: The depth of penetration may be extended to 2-3mm allowing for analysis of vascular changes in erythematous or erythropoor dermal areas. Thrombosis may be observed.

REFLECTANCE CONFOCAL MICROSCOPY: This microscopic analysis of the cells also quantifies microvascular pathology and is a potential modality for studying vasculitis.

SMALL COIL MRI: High resolution systems used for animal study and superficial organs can image the intra-arterial anatomy including dynamic contrast imaging on standard 1.5T and 3T units.

7 TESLA MRI: High field systems analyse signal abnormalites rapidly with high resolutions.

HYBRID IMAGING: Hybrid imaging refers to combining diagnostic modalities to assess disease and monitor therapy. 

TREATMENT OPTIONS

CEUS and nanoparticle delivery of dexamethasone may be used to reduce plaque inflammation and stroke occurrence. Intraarterial unstable plaque, most commonly found in the carotid artery, readily ruptures (acutely blocking flow) or dislodges causing distal embolism and arterial occlusion often in the brain, extremities and GI tract. While the composure of this plaque is mostly fibrin and lipid, it is the ulceration, bleeding and active inflammation that produces catastrophic outcomes. Neovascularization plays a central role in plaque initiation, progression and rupture. Quantifying these inflammatory microvessels is a surrogate marker of plaque instability and stroke risk. Histopathologic evidence shows plaque with high vessel density is more likely to rupture. [5]

SUMMARY

Covid-19 affliction of the arterial and venous systems with clot formation and vessel inflammation affect every organ system in the body. Arteritis of the small vessels involves the lungs, heart, brain, kidneys and liver predominantly which increases stroke risk in the absence of other contributing factors. Advanced ultrasound imaging offers early detection alerts and image guided therapeutics are now available. Anti inflammatory treatments, such as the MATH+ protocol used to treat Covid-19 pulmonary disease, might be useful in reducing intra-arterial inflammation and preventing plaque rupture.

REFERENCE

1. Hassani SN, Bard RL: Ultrasonic Diagnosis of Abdominal Aortic Aneurysms.

 J. Natl. Med. Assoc. 66:298-299, July 1974

2. Lande A, Bard RL: Arteriography of Pedunculated Splenic Cysts. Angiology 25:617-621, October 1974

3. Lande A, Bard RL, Rossi P: Takayasu's Arteritis: A World Entity. N.Y. State J. Med. 76:1477-1482, Sep 1976

4. Helbick Eur Radiol 30:5536-5538, 2020

5. Mao l  JAMA Neurol 2020 77:683-690

 

CONTRIBUTORS

ROBERT L. BARD, MD, PC, DABR, FASLMS

Advanced Imaging & Diagnostic Specialist

Dr. Bard received the 2020 nationally acclaimed Ellis Island Award for his lifetime achievement in advanced cancer diagnostic imaging. He co-founded the 9/11 CancerScan program to bring additional diagnostic support to all first responders from Ground Zero. His main practice in midtown, NYC (Bard Diagnostic Imaging- www.CancerScan.com) uses the latest in digital imaging technology and has been also used to help guide biopsies and in many cases, even replicate much of the same reports of a clinical invasive biopsy. Imaging solutions such as high-powered sonograms, Power Doppler Histogram, sonofluoroscopy, 3D/4D image reconstruction and the Power Doppler Histogram  are safe, noninvasive, and do not use ionizing radiation. 

PIERRE KORY, M.D., M.P.A.

Dr. Kory is Board Certified in Internal Medicine, Critical Care, and Pulmonary Medicine. He served as the Medical Director of the Trauma and Life Support Center at the University of Wisconsin where he was an Associate Professor and the Chief of the Critical Care Service. He is considered a pioneer and national/international expert in the field of Critical Care Ultrasound and is the senior editor of the widely read textbook “Point-of-Care Ultrasound” (winner of the President’s Choice Award for Medical Textbooks from the British Medical Association in 2015).  Most recently, Dr. Kory joined the emergency volunteer team during the early COVID-19 pandemic in NYC at Mount Sinai Beth Israel Medical Center. He is also a founding member of the Front Line COVID-19 Critical Working Group (flccc.net) composed of 5 critical care experts that devised the COVID-19 treatment protocol called MATH+. (www.covid19criticalcare.com/)

What is HIFU? High Intensity Ultrasound for the Treatment of Cancer

INTRODUCTION TO HIFU

By: Dr. Robert L. Bard  |   Graciella Davi | Editorial Staff @ NY Cancer Resource Alliance

Medical science has taken significant leaps in the past three decades with the advent of a non-invasive approach to surgical investigation and treatment modalities.  This movement was greatly prompted by the need to reduce or eliminate the many significant risks and hidden dangers of cutting through the skin and vital organs.  Technologies such as the ULTRASOUND offers the medical community life-saving alternatives that ensures quantifiable results without the  potential dangers to the patient. (also see "No More Scalpel" and "Bye Bye Biopsies")

Pursuing the concept of safe, non-surgical alternatives, the principle of HIFU is based on controllable high energy sound waves, which leads to coagulation necrosis at the focal point. It can be applied for different indications: complete ablation of prostatic tissue is attempted in whole gland HIFU in the primary treatment of localized prostate cancer. [1] The first therapeutic trial of high intensity ultrasound beams was carried out in 1942. The Fry brothers are credited with the first application of HIFU for neurologic disorders in humans. Early attempts to generate HIFU lesions in the brain through the intact skull bone were unsuccessful. Jan 10, 2011 [2]

HIFU: THE NEXT WAVE OF NON-INVASIVE CANCER TREATMENT By: Dr. Robert L. Bard 

Prostate cancer, certainly the most common cancer among men, might be considered a two-headed hydra. On the one hand, some of these tumors, especially among African-Americans are aggressive, resulting in premature death. On the other hand, many of these tumors are slow growing and for a significant subset of patients, watchful waiting is recommended. But it is difficult to watch and wait when you believe that a cancer is growing within.

The quest for minimally invasive treatments of prostate tumors has been ongoing since the 1990’s. There have been advocates of focal freezing as well as heating of prostate tissue that results in the destruction of prostate cancers. Focal cancers may be targeted by high intensity focused ultrasound beams (High Intensity Focused Ultrasound or HIFU) and have been in clinical practice for 25 years. Developed simultaneously in the US (Sonoablate 500) and France (Ablatherm) the technique is favored by men wishing to avoid possible complications or side effects of surgery or radiation therapy. 

Treatment is usually performed under anesthesia. Energy is delivered to malignant tissue using in this instance, high frequency ultrasound waves that heats the tissue above 40 degrees Centigrade destroying the tissue.  Tissue temperature is closely monitored by sophisticated electronics to minimize adjacent tissue damage which can result in narrowing of the urethrae and obstruction of the flow of urine. Additionally, nerves involved in sexual performance may be inadvertently heated resulting in some degree of sexual dysfunction. 

A recent study reported in the Journal of Urology looked at 52 patients treated with this technique. The results are mixed. Patients included all had localized biopsy proven prostate cancers. The study defined treatment failure as recurrence on follow up biopsy at 20 months showing recurrent or higher grade tumor, metastatic spread systemic therapy or cancer specific mortality. 

• There were 13 minor complications of which urinary retention was the most common.  There were no deaths and no cases of rectal injury.
• Of the 60% of individuals undergoing repeat biopsy, 83% had no residual tumor

This study was limited in two significant ways. First, nearly a quarter of the patients underwent simultaneous “debulking” of prostate tissue by conventional surgical means in order to treat pre-existing difficulties with urination. Second, if biopsy is to be considered the outcome of importance, then 40% of the patients did not complete the study. It did not recognize that microscopic analysis of biopsies is limited by the posttreatment effect on the gland and the gold standard for pathology has been whole gland analysis after radical prostatectomy.

	UCLA Offers HIFU Treatment for Recurrent Prostate Cancer- Dwight Baird's prostate cancer had returned after he initially received external beam radiation treatment 22 years ago. See how HIFU turned out to be the best solution for prostate cancer recurrence (see complete video details)
	UCLA urologist Dr. Leonard Marks discusses HIFU (high intensity focused ultrasound), an FDA-approved method for treating prostate cancer. Dr. Marks will address the advantages of HIFU over traditional treatments and its implementation at UCLA.
UCLA Health is among the world’s most comprehensive academic health systems, with a mission to provide state-of-the-art patient care, train top medical professionals and support pioneering research and discovery. It includes four hospitals on two campuses — Ronald Reagan UCLA Medical Center, UCLA Mattel Children’s Hospital and the Stewart and Lynda Resnick Neuropsychiatric Hospital at UCLA in the Westwood area of Los Angeles, and UCLA Health - Santa Monica Medical Center – and more than 200 medical practices throughout Southern California. UCLA Health also includes the David Geffen School of Medicine at UCLA.

VIEWPOINTS:

Treatment will be more effective on smaller volume glands and low grade cancer. As an imaging specialist, the problem with biopsies is that the cells under the microscope may look malignant but the tumor is clinically indolent or inactive. Biopsies are random and the area presumed to be a cancer may have active malignancy in one area, scarring in another, benign tissue adjacent or immune cells attacking the injured tissue.  Most post treatment biopsies are guided by blood vessel flow study with contrast MRI or 3D Doppler in the cancer site since PSA is not very reliable. The targeted area is the region of greatest arterial tumor arterial concentration.  [J Urol 2016]

Worldwide the aggression of a tumor is determined by the activity of the feeding blood vessels. Generally ablative treatments are deemed successful when there are no more arterial suppliers demonstrable by the various blood flow perfusion imaging technologies (Doppler ultrasound, CT dye, MRI contrast)  It is well known that there is a PSA rise in the presence of inflammation as well as recurrence which is non diagnostic. Over many years the cancer statistics observed that the re-occurrence of malignancy in 5 years falls between 10-30% regardless of the treatment delivered.

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OTHER NON-INVASIVE CANCER SOLUTIONS

ADVANCEMENTS IN PROTON THERAPY

It is commonly observed that surgeons are increasingly using minimally invasive procedures. Whether it's robotic or video assisted surgeries, we can identify the pattern of new treatment protocols to result in higher quality of life and a reduction in toxicity. In doing so, it allows us, in some cases, to actually improve survival through those same methods of reducing toxicities for patients. According to Dr. Charles B. Simone II, Chief Medical Officer of the New York Proton Center, “We’re going to see more and more customized treatment; it's not a one size fits all approach to cancer. We are going to have individualized ways to deliver radiation therapy, individualized drugs or immune agents—and then, potentially more synergy between modalities such as radiation with systemic therapies.” (See article link)

CYBERKNIFE® AND THE ERA OF ETHICS IN ENGINEERING

Today's engineering and medical technology (from the late 1980s) show significant evidence of ethical standards and major consideration for patient response. Ethics in treatment engineering covers all angles considered about the innovation including: the way it is built, the materials applied, the engagement of the operator and the aftermath of the patient.. “Historically, radiation CAUSED cancer, but that's because you didn't have precision then. You were basically irradiating healthy tissue. That's what you want to avoid at all costs. So the more precise you can be, the better - and we (Accuray) pride ourselves on exquisite and unparalleled precision,” says Ms. Fleurent. (See article link)

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About the Author:

DR. ROBERT L. BARD, MD, PC, DABR, FASLMS 

For over 40 years, Dr. Bard is recognized internationally for his advanced clinical work in non-invasive cancer diagnostic imaging. His wide body of work is catalogued in countless medical texts and journal articles about the continued advancements in quantitative 3-D Ultrasound Doppler Imaging. In addition, he has been a major advocate for early detection in many high-risk professionals such as first responders, law enforcement and military personnel. Today,  Dr. Bard continues to respond to major health crises like the Coronavirus pandemic with his collaborative research work in chest ultrasound scanning of covid-related issues and the launch of his Medical Virtualization campaign -supporting "borderless medicine" and improved technical response to emergency medical calls.

GRACIELLA DAVI is a public health and safety advocate, an environmental researcher and a publisher for Prevention101, ImmunologyFirst.org, Awareness for a Cure and (fmr) EcoSmart News.  As an educator and writer, her career is dedicated to providing FACT-CHECKED NEWS in assignments concerning health, safety, science and environmental news.  This includes a wide list of studies in Cancer causing agents and pathogenic response and medical innovations.  

REFERENCES

1) High intensity focused ultrasound (HIFU) : Importance in the treatment of prostate cancer https://pubmed.ncbi.nlm.nih.gov/28439616/#:~:text=Results%3A%20The%20principle%20of%20HIFU,treatment%20of%20localized%20prostate%20cancer.

2) High intensity focused ultrasound in clinical tumor ablation - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3095464/#:~:text=HIFU%20BACKGROUND-,History,unsuccessful%5B8%2C10%5D.

Sources: Prospective Evaluation of Focal High Intensity Focused Ultrasound for Localized Prostate Cancer Journal of Urology DOI: 10.1097/JU.0000000000001015

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From the Experts: HOSPITAL COVID INFECTION PREVENTION

By: Megan Meller, MS, MPH / Transcribed & Edited by: Lennard M. Gettz

Introduction

Months into the global pandemic, we have learned from all state and federal health agencies about the heightened standards of Covid-prevention safety measures in public areas.   As a central gathering source for infected people and potential viral transmission, hospitals require the highest level of safety codes and regulated modeling- including the care and treatment of CoronaVirus patients.  For this reason, a dedicated department in all health centers is in place to manage and enforce disease prevention protocols within the staff, the patients and the entire hospital environment. Microbiologist and public health practitioner Megan Meller, MS, MPH is a member of this department at the Gundersen Health facilities (La Crosse, WI). Her specialized work provides a significant set of keys in the fight against Covid in the front lines.

A COMMITMENT TO SAFETY EDUCATION

I am the lead infection preventionist for Gundersen Health’s outpatient clinics. My department is focused on the safety of patients and staff, and we do this through education and by carrying out an extensive list of priorities set by regulatory standards.  We maintain strict attention to the cleanliness of our work environment and ensure that equipment and instruments used during patient care are cleaned and disinfected according to industry standards.  We also help develop patient education as it relates to infectious diseases. Before Covid began, we were focusing on drug resistant bacteria and educating patients about hand hygiene and wound care.

Part of our objectives include ensuring that all safety protocols are being followed through by the nursing staff. An example of this is a group of bacteria called CARBAPENEM RESISTANT ENTEROBACTERIACEAE  (CRE)  - germs (bacteria) that can cause infections in healthcare settings and they are resistant to many antibiotics (1).  Because of the number of CRE cases a few years ago in the U.S., we ensure that all our endoscopes are cleaned and disinfected appropriately as well as setting proper guidelines in handling and storing (2). Knowing about issues like CRE is just one of many hazards in healthcare facilities where a patient’s health can be gravely affected under our care.

BURNOUT PREVENTION

The COVID-19 Pandemic has also brought attention to how BURNOUT affects patient and staff safety. For staff, this can occur when you are being overworked and or overstimulated, such that you don't have time to recover. In the case of the current pandemic, Emergency Rooms and Critical Care Units all over the country are at risk of staff exhaustion from double or triple shifts due to limited resources- especially in areas that are overrun with patients (3). Exhaustion affects your performance because it could lead to a lack of empathy and a degradation of focus which can greatly affect the patient and your safety.

To know your capacity is crucial in this job.  Staff are trained to look out for this within themselves and each other. In our facility (as with all response units), what we strive to do is WATCH OUT FOR EACH OTHER, especially in a pandemic when we're more focused on trying to stay on top of all the changes and protect patients and protect staff.  We also need to remember to put ourselves first - mentally, physically, and emotionally, or else we won’t be any good for everyone else. I need to remember daily to find time for self-care. When I am at my best, I give my best to others.

SINCE THE NEW YORK EPICENTER…

Wisconsin watched New York’s numbers back in March- and we all expected this to come to us and the rest of the country.   We all felt it was just a matter of time.  Outbreaks happen when people get complacent. When the spike surge hit Florida and Texas, we thought the Midwest got off pretty lucky with lower case numbers and deaths. But what I always try to remind my people is that, “it's just a matter of time” before our own luck runs out.  From a public health standpoint, making a difference in this pandemic is about changing behavioral patterns- and the way to do this (until you’re blue in the face) is EDUCATION- pushing to change the minds of the people. 

THE LEARNING CURVE

We did not know much about COVID-19 at the beginning of the pandemic, including how long someone remained infectious with COVID. When the CDC published their guidelines on COVID Isolation, this was a breakthrough (3). This guidance shaped our testing criteria, isolation criteria, and quarantine guidance. 

Contagious Period

Based off research compiled by the CDC, most people are infectious with COVID-19 up to two days before symptom onset and 10 days after the first appearance of symptoms (4). Scientists showed that in most cases, they were unable to collect replication-competent virus after the 10th day on infection – meaning that an individual was no longer infectious. For patients who are immunocompromised, they may be infectious for up to 20 days. This is important information because in patients with mild illness, they may continue to test positive up to 3 months after their initial infection – even when no longer contagious. We have seen this within our own population. These findings support a symptom-based strategy to isolation discontinuation rather than a test-based strategy.

This kind of information was important in how we developed patient education.  It also shaped the way we interacted with providers, because it helped identify when it was safe to bring patients back into the clinic and when to schedule surgeries and procedures.

About MASKS

In July, the CDC published a Morbidity and Mortality Weekly Report (MMWR) about cloth masks that demonstrated their effectiveness in preventing COVID-19 transmission. A CDC investigation showed that in a salon with a universal masking policy, two COVID-positive hair stylists worked while symptomatic but, remarkably, there was no reports of COVID-19 transmission among 139 clients that the stylists worked with (5). Now, other coworkers and their family members of the stylists developed COVID infections, but none of the customers—because they were wearing cloth masks and their clients were also wearing cloth masks during haircut appointments. That to me was powerful data. So to answer a common question about the effectiveness of cloth masks, once I saw that data, it was clear to me that cloth masks work and we need to educate the public to this.

We’ve seen what can happen when we overwhelm a healthcare system, like what happened in New York City and many areas across the world. Overwhelmed healthcare systems often struggle to provide care for all patients due to resource diversion which can result in poor health outcomes. Another concern is how the COVID-19 is impacting chronic disease states since many healthcare systems were redesigning care and limiting services in the wake of COVID-19 (6). In the beginning of the pandemic, Gundersen canceled elective procedures to free up hospital beds and went virtual for many outpatient appointments. Six months into the pandemic, we are fully operational but have modernized patient care. Virtual visits have become common practice at Gundersen Health for health concerns that can be addressed without an in-person appointment.

While we have been successful to date, it is still critical for the community to do their role in COVID-19 prevention through masking and social distancing. It’s hard. I get it. My mom is coming to visit this weekend for the first time since the pandemic was declared.  I told her, “okay, we will have to wear a mask around each other while we're inside together”.  That kills me to have to set these guidelines, but I don't want to get her or myself sick.

Upgrading Solutions "As We Go" 

Fighting a pandemic relies heavily on information sharing.  In the beginning, everyone was using ventilators but over time, we’ve backed off from that. Now we're using alternative ventilators like C-PAP (Continuous positive airway pressure) and BiAPS (Bilevel Positive Airway Pressure) because we learned that a COVID infection was causing a wet lung in some severe cases,  so intubating someone with a ventilator was not going to typically result in a positive outcome.  We found that we can get better outcomes by using less invasive forms of ventilation. What’s more, protocols like MATH+ (use of Methylprednisolone) all ties into this because WE LEARN AS WE GO.  The global community of health care professionals all learn what works and what doesn't work and what might be more effective. And the more we publish new findings and the more we share and connect with each other, the faster we're going to get to an antiviral solution whether it's something that's already on the market or a brand-new technology.

LIFE OF THE VIRUS

One of the questions I get a lot is about a vaccine, and viral dynamics. We know that there is pressure for viruses to evolve in ways that maintain their ability to transmit from person to person.  We call it “natural selection.” Some respiratory illness, with time, may evolve to be more contagious but not as deadly. What I hope happens with COVID-19 is that it evolves in this manner to be less severe but only time will tell.

I see COVID-19 eventually becoming more like the flu where it occurs every year. Perhaps 50 years from now or even let's say 10 years from now- COVID may look more like another common cold because it's found its sweet spot where it can keep infecting people without causing the same magnitude of severe illness that we  are currently seeing. We're in an incredible age of technology and pandemics encourage innovation. So I do think we will eventually have a vaccine for COVID-19 but it might be one we have to get every single year because the virus is going to keep evolving and we need to just stay on top of it- like we do with the flu.

REDUCTION IN MORTALITY

A lot of factors are important when it comes to reducing the number of cases (and mortality) linked to COVID-19. I believe masking and social distancing can play a major role in the reduction if enough people adhere to them. The current state of COVID immunity is still being investigated and that too impacts case numbers.

Predicting all this also makes a big difference in prevention. While we're not seeing a surge of deaths and hospitalizations in our area yet, we're seeing other manifestations of COVID-19.  In Wisconsin, we are testing more people than we were in the beginning of the pandemic and we are more compliant with masking.  COVID-19 has made all of us in healthcare much more attuned to prevention measures like isolation precautions, personal protective equipment, and environmental cleaning. At Gundersen, we stress that where and who you take your lunch break with can increase your risk for getting COVID.  In my department, we used to eat lunch together huddled around a table, talking and laughing. Now we eat our lunches separately at our desks because it is safer.

HEPA FILTRATION VS AIRBORNE PRESENCE OF SARS-COV-2 IN HOSPITALS

Recent headlines show evidence of Coronavirus pathogens in hospital air supply and air passageways- creating a systemic hazard for the staff and patients under critical care. Substantial controversy about the role played by SARS-CoV-2 in aerosols in disease transmission, due in part to detections of viral RNA but failures to isolate viable virus from clinically generated aerosols. As of March 30, 2020, approximately 750,000 cases of coronavirus disease (COVID-19) had been reported globally since December 2019 (1), severely burdening the healthcare system (2). The extremely fast transmission capability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has aroused concern about its various transmission routes. This study led to 3 conclusions.  (see complete article)

WHAT'S THE DIFFERENCE BETWEEN ASYMPTOMATIC AND PRE-SYMPTOMATIC?
By: Megan Meller, MS, MPH
There has been a lot of news coverage about how COVID-19 is spread. Someone who is asymptomatic has the infection but no symptoms and will not develop them later. Someone who is pre-symptomatic has the infection but don't have any symptoms yet. Both groups can spread the infection. COVID-19 spreads easily and we believe that's because it's spread by those who don't know they're infected. We suspect that individuals who are pre-symptomatic are infectious for two to three days before having symptoms. (see complete article in GundersenHealth.org)

ABOUT THE AUTHOR

MEGAN MELLER, MS, MPH is an Infection Preventionist with Gundersen Health System based in La Crosse, Wisconsin. From a young age, Megan has been passionate about science and the world of infectious diseases. Megan received her Master of Science in Microbiology at Indiana University-Bloomington where she studied alphavirus replication and her Master of Public Health (MPH) from the University of Wisconsin School of Medicine and Public Health. While working on her MPH, Megan worked closely with Infection Control departments and the communicable disease section at the Wisconsin Department of Health Services. In her current role, Megan is the lead Infection Preventionist for Gundersen’s outpatient departments and works closely with infection control partners located at regional hospitals. Megan is also a media consultant for the Infection Control and Infectious Disease departments and serves as an infection control consultant for numerous organizational groups.  

REFERENCES

1. CDC Statement: Los Angeles County/UCLA investigation of CRE transmission and duodenoscopes. Centers for Disease Control and Prevention. July 10, 2015. https://www.cdc.gov/hai/outbreaks/cdcstatement-la-cre.html

2. Transmission of multi-drug resistant bacteria via ERCP. American Society for Gastrointestinal Endoscopy. https://www.asge.org/home/about-asge/newsroom/transmission-of-cre-bacteria-via-ercp 

3. Sasangophar et al (2020). Provider Burnout and Fatigue During the COVID-19 Pandemic: Lessons Learned From a High-Volume Intensive Care Unit. Anesth Analg.

4. Duration of Isolation and Precautions for Adults with COVID-19. Centers for Disease Control and Prevention. Updated August 16, 2020. https://www.cdc.gov/coronavirus/2019-ncov/hcp/duration-isolation.html

5. Absence of Apparent Transmission of SARS-CoV-2 from Two Stylists After Exposure at a Hair Salon with a Universal Face Covering Policy – Springfield, Missouri, May 2020. Morbidity and Mortality Weekly Report. Centers for Disease Control and Prevention. July 17, 2020. 69:28.

6. Chudasama et al (2020). Impact of COVID-19 on routine care for chronic diseases: A global survey of views from healthcare professionals. Diabetes and Metabolic Syndrome: Clinical Research and Reviews. 14:965-967.

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VIEWPOINTS

TERI HULETT, RN, BSN, CIC, FAPIC - Denver, CO
 COVID-19 changed life as we knew it, highlighting infection prevention (IP) gaps across the spectrum of healthcare settings – especially in long-term care (LTC). IP in acute care has been an emphasis for years. I believe the work that has occurred in acute care can be applied in LTC. While Megan’s article focused on the hospital setting, COVID-19 underscored how the LTC setting was woefully unprepared for the impending tragedy. This article addressed the overwhelmed healthcare system, the demand for ongoing education, and the call for community engagement – all key to preventing transmission regardless of the setting.  IP in LTC has not been given the attention it needed or deserved. The infection preventionist in LTC usually wears multiple hats and is forced to juggle priorities. I believe the new normal will change IP across all settings as IP outside acute care directly impacts the acute care setting. (www.ipstrategies.org)

RODNEY CHENG, MD - Los Angeles, CA
COVID-19 has been responsible for a lot of economic hardships, disrupted a lot of lives, and killed a lot of people. Despite this- we can take away some positives from the pandemic and this article touches on them. There is an overdue emphasis on safety and personal protection. Who knows what the new normal will be, but at the very least, if we learn to wear masks when we are sick and wash hands often, this will have been an invaluable lesson. This article does a great job of explaining why this virus is effective as a disease vector. Lastly, it’s amazing to see scientists and health experts race to characterize the disease, and base protocols on good data. Given that virus shed from patients after 10 days are no longer replication competent, it’s reasonable and important to proceed with critical health services if asymptomatic.

KATELYN HARMS, MPH, CIC - Madison, WI

Infection Prevention’s response to COVID has evolved as rapidly as the data is published.  Unlike most science and research, the general public has been along for the journey- as everyone has been updated through media about each research breakthrough, failed trial, and vaccine development phase.  The ebbs and flows of scientific discovery are challenging to translate, as success is not always linear.  As this article points out, healthcare has made tremendous progress in understanding the virus and how to prevent transmission.   But maintaining the public’s engagement with prevention measures will continue to be challenging.  It’s important for science communicators to continue spreading facts and translating complex concepts into relatable and clear guidance.   Infection Preventionists will continue to support the safety of our patients and healthcare workers.  But managing this pandemic relies on support from everyone both inside and outside the healthcare setting.  

SUMAN RADHAKRISHNA, MD FACP - Los Angeles, CA

COVID continues to disrupt societal structure and our lifestyle this fall.  Schools, colleges, nonessential workers are still learning and working from home.  Zoom, common to comic book readers, is now a household word.  Social distancing is now becoming physically and emotionally isolating.  Small and large gatherings are epicenters for community outbreaks.  How do we proactively work to control the spread of this disease?   This is a good time to update our vaccination status and receive the influenza vaccine.  Pharmacies and clinics can schedule appointments for vaccination.   Vaccines for COVID are in clinical trials.  Wearing a mask, washing/sanitizing hands, and social distancing reduces respiratory viral infections in addition to COVID.  When transmission is controlled, restrictions ease allowing resumption of work and social activities.  All of us have a crucial role to play in this process.   Let us commit to proactively control COVID transmission.

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A natural health ingredient known as FUCOIDAN has joined our western fight against cancer  -native to the cold temperate seas of China, Japan, Korea. According to Memorial Sloan Kettering Cancer Center, "Fucoidan is a complex polysaccharide found in many species of brown seaweed .... shown to slow blood clotting. Laboratory studies suggest that it can prevent the growth of cancer cells and has antiviral, neuroprotective, and immune-modulating effects."

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Hospital Air Shows Heavy Presence of SARS-Cov-2  July 23, 2020 - Recent headlines show evidence of Coronavirus pathogens in hospital air supply and air passageways- creating a systemic hazard for the staff and patients under critical care. Substantial controversy about the role played by SARS-CoV-2 in aerosols in disease transmission, due in part to detections of viral RNA but failures to isolate viable virus from clinically generated aerosols.  Active study from the University of Florida states: "Air samples were collected in the room of two COVID-19 patients ... Those with respiratory manifestations of COVID-19 produce aerosols in the absence of aerosol-generating procedures that contain viable SARS-CoV-2, and these aerosols may serve as a source of transmission of the virus".

Disclaimer & Copyright Notice: The materials provided on this website are copyrighted and the intellectual property of the publishers/producers (The NY Cancer Resource Alliance/IntermediaWorx inc. and Bard Diagnostic Research & Educational Programs). It is provided publicly strictly for informational purposes within non-commercial use and not for purposes of resale, distribution, public display or performance. Unless otherwise indicated on this web based page, sharing, re-posting, re-publishing of this work is strictly prohibited without due permission from the publishers.  Also, certain content may be licensed from third-parties. The licenses for some of this Content may contain additional terms. When such Content licenses contain additional terms, we will make these terms available to you on those pages (which his incorporated herein by reference).The publishers/producers of this site and its contents such as videos, graphics, text, and other materials published are not intended to be a substitute for professional medical advice, diagnosis, or treatment. For any questions you may have regarding a medical condition, please always seek the advice of your physician or a qualified health provider. Do not postpone or disregard any professional medical advice over something you may have seen or read on this website. If you think you may have a medical emergency, call your doctor or 9-1-1 immediately.  This website does not support, endorse or recommend any specific products, tests, physicians, procedures, treatment opinions or other information that may be mentioned on this site. Referencing any content or information seen or published in this website or shared by other visitors of this website is solely at your own risk. The publishers/producers of this Internet web site reserves the right, at its sole discretion, to modify, disable access to, or discontinue, temporarily or permanently, all or any part of this Internet web site or any information contained thereon without liability or notice to you.

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Which Corticosteroid is Best for SARS-CoV-2?

“Problem-solving leaders have one thing in common: a faith that there’s always a better way.” – Gerald M. Weinberg

DEXAMETHASONE VS. METHYLPREDNISOLONE

Produced by: Lennard M. Gettz & Dr. Robert L. Bard

Edited by: FLCCC Technical Team

August, 2020- the current status of the Coronavirus pandemic keeps up a healthy dose of conflicting global news headlines (ranging in levels of scientific validity) as far as potential treatment solutions and vaccines.  Countless research groups and clinical trials world-wide bear differing fruits, one closer to the end game than the next.

By June, the W.H.O. launched the headline “Preliminary results about dexamethasone use in treating critically ill COVID-19 patients” [5].  This was echoed immediately by countless European news sources with encouragement like “Dexamethasone to be the proven first life-saving drug”- forming a global cascade of targeted positivity and market demand from a world so desperate for a cure.

Publicly recognized by health agencies like the NIH who stated, “Patients with severe COVID-19 can develop a systemic inflammatory response that can lead to lung injury and multisystem organ dysfunction. It has been proposed that the potent anti-inflammatory effects of corticosteroids might prevent or mitigate these deleterious effects” [1]

A unique insight into this disease showed that the majority of patients initially present with an inflammatory reaction in the lungs called “organizing pneumonia,” which is the body’s reaction to injury and has been well known to be profoundly responsive to corticosteroid therapy. If the organizing pneumonia response is left untreated or presents as a rapidly progressive sub-type, a condition called Acute Respiratory Distress Syndrome (ARDS) follows.

STRATEGIC TREATMENT CHALLENGE FROM THE FIELD

Meanwhile, teams of American physicians like Dr. Pierre Kory, Pulmonary and Critical Care Specialist (Milwaukee, WI) and his team of front-line Covid care providers (the Front Line Covid-19 Critical Care Alliance) challenged Dexamethasone as the exalted panacea of the pandemic.  Dr. Kory’s team dedicated their life’s work to the research and treatment of infectious diseases in critical illness, and recently published a battle-tested and proven Hospital Treatment Protocol called MATH+,  a combination of medicines designed to counteract the injurious hyperinflammation, hypercoagulability, and hypoxemia in COVID-19 using synergistic actions. Their group strongly recommends a different corticosteroid called METHYLPREDNISOLONE.   Work done by members of the group, in particular, Dr. G. Umberto Meduri, one of the worlds experts on the use of corticosteroids in critical illness, discovered key findings establishing the rationale in support of the preferred use of Methylprednisolone, while also providing a wider scope of evidence supporting corticosteroid therapy for Covid-19 critical cases.

According to Dr. George P. Chrousos (Athens, Greece), leading international expert on glucocorticoids, he detailed conclusive evidence about  "homeostasis and the “surprise” of effective glucocorticoid therapy" in a recent medical report with Dr. G. Umberto Meduri (7/2020, Elsevier/Science Direct).  His summary included-- "...on the basis of our understanding of the pathophysiological mechanisms of critical disease, one can conclude that the onset of therapy with glucocorticoids and, possibly, other useful or potentially useful agents in severe COVID-19 must take place early, before the homeostatic mechanisms of the organism reach complete, irreversible exhaustion. ... It is questionable whether dexamethasone is more efficacious than other synthetic glucocorticoids when given in equivalent doses. One potential advantage is the almost complete lack of salt-retaining activity of this corticosteroid. As the pleiotropic actions of ascorbic acid, vitamin D, and thiamine include assisting glucocorticoids and mitochondria in the change of the homeostatic immune balance from proinflammatory to anti-inflammatory, it is best for the patients to have sufficient reserves of these rapidly depleted micronutrients. This treatment approach is incorporated into the MATH+ (methylprednisolone, thiamine, ascorbic acid, heparin) protocol (https://covid19criticalcare.com). [6]

BACKGROUND

Between March of 2013, and Dec of 2018, a research group in Spain conducted a multi-ICU randomized trial to treat ARDS to an estimated 250 patients. It resulted in higher ventilator-free days in the DEXAMETHASONE group than in the control group. By day 60, 21% of the patients in the Dexamethasone group and 36% of the patients in the control group had died. [2] This randomized controlled trial showed profound benefits to treating ARDS with Dexamethasone.

A more recent study between Jan-Feb of 2020 at the isolation ward of the Union Hospital of Huazhong University of Science and Technology in Wuhan, China reported much higher survival rates among the 84 patients with severe COVID-19 pneumonia that were treated with early, low-dose Methylprednisolone compared to those who did not receive such treatment. Because this is was an early observational study, it encouraged later and larger randomized controlled trials to confirm the findings and further study the mid- and long-term outcomes after discharge.

Other studies continued with varying patient numbers and severity of illness (ie. respiratory distress, elevated respiratory rates and significantly diminished oxygen saturation), all seeking comparative clinical outcomes of COVID-19 pneumonia patients with or without Methylprednisolone treatment. [3] This studies concluded that “early administration of methylprednisolone could reduce duration of mechanical ventilation and overall mortality in patients with established moderate-to-severe ARDS”.

COVID ARDS / PNEUMONIA:

Chinese cohort, ARDS, Wuhan – 84 ARDS patients, 46% mortality with MethylP, 62% if no MethylPrednisolone [7] HR=.38 (62% reduction in death) Other COVID Studies, all using MethylPrednisolone 1) HFHS Trial, Detroit, Fadr R- showed a 45% RR, with early MP compared to 29% with dexamethasone in Recovery Trial 2) French study - steroids reduced rate of intubation from 51% to 8.6% - massive 3) Glucocovid trial - 50% Risk reduction for NIV, INTUBATION/DEATH Iin all, it was less ICU, in young it was less death) 4) Canfolanieri Trial from Italy- mortality was reduced from was 23.3% to 7.2%- a 69% relative reisk reduction (RRR), compare this to Recovery trial which had an RRR of 29% if on MV and 20% if on oxygen.

NON-VIRAL ARDS:
1 Trial using DEXAMETHASONE (277 patients) -LANCET “DEXA-ARDS’ TRIAL (Villar 2020) – increased MV-free days by 4.8 -duration of MV decreased by 5.3 - Number need to treat to save a life using absolute mortality difference = 8	4 Trials using METHYPREDNISONE (322 patients) (Meduri, 1998, 2007, Steinberg 2006, Rezk 2013) – increased MV free days by 8.5 -duration of MV decreased by 10.1 - Number need to treat to save a life using absolute mortality difference = 5.3	5 Trials using HYDROCORTISONE (494 patients) (Confalonieri, 05, Annane, ’06, Sabry, ’11, Liu, ’12, REzk, 2013, Tongyoo, 2016 -increased MV free days by 4.0 -Number need to treat to save a life using absolute mortality difference = 9.7

CONCLUSION

From the viewpoint of treatment strategy, Dr. Kory and his colleagues offer their assessment based on active historical data of mortality and an evidence based review; “the number needed to treat (NNT) to save one life with a therapy is calculated by dividing the absolute risk reduction associated with the treatment into 100. So let's say 80% of patients die and you get it down to 60%, that's an absolute risk reduction of 20. And that means you only need to treat five patients to save one life. And so we tend to estimate the potency of a life-saving therapy using the NNT. The NNT to save a life in ARDS with Methylprednisolone is about five and the number needed to treat to save a life with Dexamethazone using the existing studies is about eight based on old ARDS studies and in COVID it appears much higher than 8. And so when we're trying to advocate for use of methylprednisone, we’re doing so due to the fact that many more real lives could be saved, given the large difference in the efficacy of the two drugs."

If you can treat five patients and save a life (with one drug), whereas it takes eight patients to save a life with another drug (within your first 10 patients of) using Dexamethazone, you may have missed the opportunity to save a couple of lives - hence we emphasize the need for Methylprednisolone.

Trials are still going on, some are randomized control trials and cohort trials using methylprednisolone, including a famous one that received early attention from Henry Ford health System in Detroit, MI, another recently came out of Italy and another one from France. Those trials using methylprednisolone showed much more dramatic benefits- showing a reduction in mortality by 70%!  That's a significant number as far as saving lives.

Another study published in May, 2020, based on work done by a company called Advaita Bioinformatics, Dr. Sorin Draghici led a team that reviewed the comprehensive genetic database which lists the pattern of activation of all the hundreds of genes that are activated in cells cultured with SARS-CoV-2 (the virus that causes COVID-19). Almost all the genes produced inflammatory mediators,protein, cytokines and chemokines.

Advaita then used their database of several thousand medicines in which they had catalogued  the patterns of “gene suppression” induced by the medicines, and then they tried to find the “best match” that counteracted the pattern of activation. They did this for different viruses including H1N1 and SARS-CoV-2. At the conclusion of an extensive analysis, they found that the medicine whose suppression pattern most closely matched the activation pattern of SARS-Co-V2 was METHYLPREDNISOLONE. And on this top 10 list of matches, DEXAMETHAZONE WAS 6th.  Furthermore, according to their report, the researchers repeatedly stated that they didn't think that Dexamethasone would work very well. Hence, this genomic analysis review strongly supported the use of Methylprednisolone over dexamethasone. [4]

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EPILOGUE: 

BEDSIDE DETECTION WITH DOPPLER ULTRASOUND IMAGING

by: Dr. Robert L. Bard

In reviewing the genes activated by SARS-CoV-2, almost all were for inflammatory proteins / cytokines / chemokines. A study of the gene “suppression” activity of a large number of medications has suggested the one medicine that best neutralized activity of the virus was methyprednisone. A new screening approach that provides real time evidence of clinical effect is the use of 3D high resolution lung ultrasound on the pleural surface and Doppler flow imaging on the inflammatory vascular dilation and blood velocity.

Lung ultrasound relies on the images produced by artifacts: A-lines from normal pleura, B-lines from abnormal pleural-parenchymal disease and increased Doppler flow in consolidations that are pleural based.

Survivors are experiencing either new organ system disorders or complications of ventilator dependency and pulmonary fibrosis. CT and ultrasound are useful in the investigation of these disorders and useful in follow up of potentially chronic conditions.  While lung CT abnormalities attain greatest severity approximately 10 days after onset of symptoms and tend to reduce after 14 days during the absorption phase with patients achieving normal living ability by about 2 months after onset, CT findings may remain apparent. CT images in the early recovery phase show reduction of GGO and reduced consolidation but pulmonary fibrosis appears as fibrous shadows such as fibrous stripes, subpleural lines and traction bronchiectasis in multiple lung lobes. This finding has been documented previously in SARS patients discharged after treatment. One can follow up fibrosis with non radiation imaging such as chestwall elastography and diaphragmatic ultrasound to compare with clinical respiratory evaluation.

In the months following patients with very minimal CT images, the clinical symptoms in some progress due to a chronic fibrotic response even as the imaging findings improve. This makes the pleural findings an important parameter and suggests initial and serial follow up with non invasive high resolution 3D ultrasound with elastographic scanning. The normal pleural thickness at 18 MHz linear transducer imaging is 0.3mm to 0.5mm and the normal pleural echo may be inhomogeneous due to the expected respiratory motion. Similarly, the expected A-lines  have the same features . A pathologically thickened pleura line is optimally imaged with a 3D 17 MHz linear probe or 18 MHz convex probe.  The diaphragmatic pleural interface is important since most of the pathology is found in this area which has some B-line activity in recumbent positions or in elderly patients so the pleural thickness is helpful in determining disease aggression. A thin pleural line with good respiratory excursion suggests healthy tissues.  Inflammatory or neoplastic hepatic or splenic disorder may cause attenuation of deep pleural echoes.

Doppler imaging of pleural based pneumonic consolidations shows increased blood flow in aggressive disease which decreases as the pneumonia improves or recedes from chestwall pleural contact. This novel approach is undergoing clinical study and has been used to differentiate benign from malignancy that is pleural based.

SUMMARY

Real time imaging of the pleural thickness is a surrogate marker for treatment effect. A pleural A-line that remains the same or reduces in thickness means pharmacologic drug effect is effective. Conversely a thickening line implies disease progression. Similarly, Doppler flow decreasing in a pleural based consolidation is a positive sign of clinical impact.

CONTRIBUTORS

ROBERT L. BARD, MD, PC, DABR, FASLMS

Advanced Imaging & Diagnostic Specialist

Dr. Bard received the 2020 nationally acclaimed Ellis Island Award for his lifetime achievement in advanced cancer diagnostic imaging. He co-founded the 9/11 CancerScan program to bring additional diagnostic support to all first responders from Ground Zero. His main practice in midtown, NYC (Bard Diagnostic Imaging- www.CancerScan.com) uses the latest in digital imaging technology and has been also used to help guide biopsies and in many cases, even replicate much of the same reports of a clinical invasive biopsy. Imaging solutions such as high-powered sonograms, Power Doppler Histogram, sonofluoroscopy, 3D/4D image reconstruction and the Power Doppler Histogram  are safe, noninvasive, and do not use ionizing radiation. 

PIERRE KORY, M.D., M.P.A.

Dr. Kory is Board Certified in Internal Medicine, Critical Care, and Pulmonary Medicine. He served as the Medical Director of the Trauma and Life Support Center at the University of Wisconsin where he was an Associate Professor and the Chief of the Critical Care Service. He is considered a pioneer and national/international expert in the field of Critical Care Ultrasound and is the senior editor of the widely read textbook “Point-of-Care Ultrasound” (winner of the President’s Choice Award for Medical Textbooks from the British Medical Association in 2015).  Most recently, Dr. Kory joined the emergency volunteer team during the early COVID-19 pandemic in NYC at Mount Sinai Beth Israel Medical Center. He is also a founding member of the Front Line COVID-19 Critical Working Group (flccc.net) composed of 5 critical care experts that devised the COVID-19 treatment protocol called MATH+. (www.covid19criticalcare.com/)

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REFERENCES

1) Corticosteroids (Last Updated: July 30, 2020) Recommendations for Patients with COVID-19

https://www.covid19treatmentguidelines.nih.gov/immune-based-therapy/immunomodulators/corticosteroids/#:~:text=Patients%20with%20severe%20COVID%2D19,or%20mitigate%20these%20deleterious%20effects.

2) Dexa randomized multi-unit test in Spain/ https://pubmed.ncbi.nlm.nih.gov/32043986/

3) A retrospective cohort study of methylprednisolone therapy in severe patients with COVID-19 pneumonia https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186116/

4) Wayne State spinoff Advaita Bioinformatics identifies generic drug shown to be effective against COVID-19 (Wayne State Univ) https://today.wayne.edu/news/2020/05/12/wayne-state-spinoff-advaita-bioinformatics-identifies-generic-drug-shown-to-be-effective-against-covid-19-37290

5) WHO welcomes preliminary results about dexamethasone use in treating critically ill COVID-19 patients https://www.who.int/news-room/detail/16-06-2020-who-welcomes-preliminary-results-about-dexamethasone-use-in-treating-critically-ill-covid-19-patients

6) Critical COVID-19 disease, homeostasis, and the “surprise” of effective glucocorticoid therapy - https://www.sciencedirect.com/science/article/pii/S1521661620307002

7) A retrospective cohort study of methylprednisolone therapy in severe patients with COVID-19 pneumonia  https://www.nature.com/articles/s41392-020-0158-2

Epilogue References:

7) Covid-19 Symposium-Italian Experience 2020   European Society of Radiology March 2020

8) Bard R 2021 IMAGE GUIDED TREATMENT OF COVID-19 LUNG DISEASE Springer(in press)

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Killer Breath Contained in NewTek Imaging

Initially, there was a great deal of reluctance in accepting the belief that COVID-19 could be transmitted via airborne means.  To explain this, the Schlieren imaging technique by LaVision puts the debate to rest- by showing in real time how BREATH travels. See how vapors & droplets in your exhaled CO2 can deploy as you speak, cough, laugh or sneeze WITH and WITHOUT a mask. This video helps explain how viral contamination occurs. (See video)

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