Tuesday, May 3, 2022

GENOMIC TESTING: THE FOUNDATION TO PERSONALIZED HEALTH



GENOMICS 101
Genomics is the study of all of a person's genes (the genome), including interactions of those genes with each other and with the person's environment.  An organism's complete set of DNA is called its genome. Virtually every single cell in the body contains a complete copy of the approximately 3 billion DNA base pairs, or letters, that make up the human genome. With its four-letter language, DNA contains the information needed to build the entire human body. A gene traditionally refers to the unit of DNA that carries the instructions for making a specific protein or set of proteins. Each of the estimated 20,000 to 25,000 genes in the human genome codes for an average of three proteins.

Virtually every human ailment has some basis in our genes. Until recently, doctors were able to take the study of genes, or genetics, into consideration only in cases of birth defects and a limited set of other diseases. These were conditions, such as sickle cell anemia, which have very simple, predictable inheritance patterns because each is caused by a change in a single gene.

The Human Genome Project was designed to generate a resource that could be used for a broad range of biomedical studies. One such use is to look for the genetic variations that increase risk of specific diseases, such as cancer, or to look for the type of genetic mutations frequently seen in cancerous cells. More research can then be done to fully understand how the genome functions and to discover the genetic basis for health and disease.




ESSENTIALS OF GENOMIC TESTING
By: Dr. Roberta Kline

DNA (deoxyribonucleic acid) makes up the genes that contain the blueprint for how our bodies operate ‐ from energy production in mitochondria to walking and breathing, from cellular health to digesting food, from thinking and running to protection from viruses, how we age and more. While humans are 99.9% alike in our DNA, it's the difference in that 0.1% that makes us each unique. Much of that difference comes from millions of small changes in our DNA.

Genomic testing focuses on these small changes in DNA called single nucleotide polymorphisms (SNPs) that potentially predispose to disease or problems with medications by altering the body's biochemistry. But knowing about these potential areas of weakness is just the first step. The powerful part is that we know how to modulate their impact, thus potentially changing the outcome by reversing course, delaying onset or even preventing a disease process altogether.

By decoding the instructions contained in DNA, each person becomes empowered with their own operating manual as to what they need for health. They can let go of the struggle as their blueprint guides them to the diet, lifestyle, exercise, supplements and medications that are best suited to their genes. And because we are only human, when life throws a curveball, having this personalized roadmap helps to get back on track much faster and with more precision.

  • Nutrigenomics evaluates DNA to provide personalized diet, lifestyle, supplement and exercise recommendations for prevention and disease management strategies.
  • Oncogenomics is a sub-field of genomics that characterizes cancer-associated genes. It focuses on genomic, epigenomic and transcript alterations in cancer.
  • Pharmacogenomics evaluates DNA to provide personalized medication guidance for current and/or future medications.



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 MedTech Review: Global Advance in DNA Sequencing and the Genomic Testing Market

According to industry reports, the global genomics market is projected to reach USD 54.4 billion by 2025 from USD 22.7 billion in 2020, at a CAGR of 19.0% during the forecast period. [1] The fast growing popularity of this diagnostic paradigm (both from the consumer and the clinical communities) is due to the rising support from government funding and the ever-increasing need for cancer research and solutions- all adding to increasing number of labs, technologies and experts in the market. The "genomics revolution" highlighted by the sequencing of the human genome, touts a scientifically innovative approach to disease diagnostics- and offering a promise of supporting prevention and patient care. The potential to improve the economics of scale of healthcare from advanced scanning is a global necessity, but according to the World Health Organization, approximately 80% of investments in genomics in 2000 were made in the United States, and 80% of the DNA patents in genomics in the period 1980 through 1993 were held by US companies. [2]


Advancements in sequencing, from 2D sequencing (1970s) to DNA sequencing have continually improved in data access and reporting - whereby platforms, such as Illumina/ Solexa, ABI/ SOLiD, 454/Roche, and Helicos, have provided unique prospects for high-throughput functional genomic research. After the introduction of NGS technologies in 2005, they have had an incredible influence on genomic research. Currently, next-generation sequencing has its application in the diagnosis of a variety of illnesses, such as cancer, hematological disorders, neurology, psychiatry, dysmorphology, vision and hearing impairment, cardiology, and pharmacogenomics.[3]

As with all markets, accessibility follows the direction of affordability, whereby the popularity of Genomic testing reflects the lowering cost per raw megabasse of DNA sequencing. The image (insert) shows the cost-accounting data summarizing (1) "Cost per Megabase of DNA Sequence" and the cost of determining one megabase (Mb; a million bases) of DNA sequence of a specified quality [see below]; (2) "Cost per Genome" - the cost of sequencing a human-sized genome.[4] 





GENOMIC TESTING: A DIAGNOSTIC INNOVATION FOR PREDISPOSITION SCANNING

In a 2022 review by NYCRA-NEWS, a consistent and rapid growth in the GENOMICS TESTING market indicates promise and confidence in the diagnostic community.  Since the mapping of the human genome in 2003, the ability to offer a patient's physiological blueprint cemented a sound way of safely, accurately and cost-effectively identifying PRE-DISPOSITION.[1]  It is also widely recognized for 
diagnosing, monitoring, treating, possibly preventing and even predicting disease, as well as promoting good health in individuals, across communities and whole populations. [2]

Through a simple oral swab, saliva or blood test, a sequencing lab can output countless bits of information about the patient's DNA and how it impacts physiology and predisposition to disease..  To some, certain tests can help formulate a proper (and safe) treatment plan that is custom-designed for that specific patient (otherwise known as PERSONALIZED MEDICINE). The same area of study can help recognize a patient's potential adverse reaction (side effects) to medicines.

DNA testing is not new. Genetic sequencing (detecting for hereditary cell mutations) has been around since the 70's. The Human Genome Project, which was completed in 2003, mapped all 3 billion letters of the human genome and identified est. 20,000 genes. [3] 20 years into this, the market continues to expand and investment is equally high.  The data is solid and diagnostics on the cellular level is part of our modern medical reality.

Growth in subscription to genomic testing by medical/healthcare practices have found significant advantages:

1) Under the supervision of an experienced interpretation specialist and a reputable lab, getting a patient's genetic road-map can offer a significantly streamlined and intelligent patient care strategy for genetic  treatment and possibly prevention of most diseases.  A genomic test can offer a highly focused or a more generalized view into each person's DNA makeup as needed. 

2) Genomic testing increases the professional capacity of any provider by offering one of the most modern, accurate and highly quantifiable diagnostic readings of the entire patient.  This effective and highly detailed patient reporting is a highly manageable and expandable diagnostics to support many treatment strategies.

3) Genomics can be the core modality behind any PREVENTION or RISK REDUCTION program as part of personalized medicine.



References: 
1) "Genetic Test Availability And Spending: Where Are We Now? Where Are We Going?" -  https://www.healthaffairs.org/doi/10.1377/hlthaff.2017.1427
2) "Genomic Testing for Human Health and Disease Across the Life Cycle: Applications and Ethical, Legal, and Social Challenges": https://www.frontiersin.org/articles/10.3389/fpubh.2019.00040/full


VIEWPOINTS

"The possible applications of genomic medicine are simply astounding to me. Truly, I can imagine boundless potential for harnessing this vital information and developing greater understanding of the impact of our genome on disease development, prevention, and treatment. As a physical therapist, the potential for disease prevention and holistic care of individuals through genome sequencing and lifestyle modification is so exciting. As a mother of two children who have been affected by a rare disease, viral myocarditis, without an identified genetic correlate, knowing more about how their genetic code impacts their disease presentation as well as improving efficient diagnosis and developing precision treatment methods would be absolutely life changing. We are living in an exciting time, and I'm thrilled to see the future of genomic medicine unfold in its many presentations!" - JANA ROJAS, PT / CEO of the For Elysa Foundation www.forelysa.org

"As a skincare professional and esthetics educator, the idea of having genetic information to create highly individualized skincare treatment plans and homecare regimens that will be specifically tailored based on the scientific evidence present in the interpretation of your DNA sequencing, seems like some sort of Star Trek episode where Lt. Uhura goes to the spa. This is going to revolutionize the skincare industry and those skincare professionals who are early adapters are going to thrive! Investing in a relationship with an experienced interpretation specialist and a reputable lab will offer an intelligent consultation and analysis process that will strategically recommend the most advanced treatments and topical skincare for clients’ skin health" - MARY NIELSEN, Spectrum Advanced Aesthetics Institute

"Wow! I keep thinking about the possibilities that genomic testing can [bring not only to] perfectly describe what your health future could be but as a PEMF specialist it gives me the opportunity to target specifically with scientific evidence your 3 billion letters of your DNA containing more than 20,000 genes. This would allow me to establish a very precise [PERSONALIZED] program, not only for your current health problem, but first and foremost, in a preventive approach. It would also help your doctor to make a quick and efficient diagnosis of any possible disease with proper prescribed medication in the first instance."   
- JOSEPH JOCELYN TOY, Therapeutic Specialist - (www.cliniquesneuroviesante.com)    




REFERENCES

1) https://www.marketsandmarkets.com/Market-Reports/genomics-market-613.html

2) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1447192/

3) https://www.globenewswire.com/en/news-release/2020/12/09/2142102/28124/en/Global-DNA-Sequencing-Market-2020-to-2025-Growth-Trends-and-Forecasts.html

4) NHGRI: https://www.genome.gov/about-genomics/fact-sheets/DNA-Sequencing-Costs-Data

5) https://www.marketdataforecast.com/market-reports/north-america-genomics-market

6) https://www.prnewswire.com/news-releases/north-america-genomics-market-2017-2019--forecast-to-2025---growth-in-investments--funds-for-genomics--declining-cost-of-sequencing-procedures-300853943.html

Monday, May 2, 2022

LONG HAUL SYNDROME: THE POST-COVID DISORDERS

In our upcoming spotlight, we will explore and discuss the "most exhaustive studies on the permanent effects of the coronavirus" and the enclosed diagram on the many long term effects of Covid-19. Our editors are honored to present the exculsive interview with Dr. Sonia Villapol, a highly published and most well regarded international researcher for the highest health disorders of our time. Dr. Villapol has dedicated her focus on elucidating the mechanisms of neurodegeneration, neuroinflammation or neurogenesis via several models of brain injury (traumatic brain injury or cerebral ischemia), and how inflammatory mediators connect the brain with the periphery.  Dr. Villapol has received extramural research funding as Principal Investigator from NIH and was was awarded with an R03-NIH grant to study the neuropathology of brain damage, and more recently an R21-NIH grant to study the role of microbiome in the neuropathology of traumatic brain injury.


REPORT: Long COVID in Children and Adolescents
Submitted by: 
Sonia Villapol | doi: https://doi.org/10.1101/2022.03.10.22272237

Posted March 13, 2022

ABSTRACT: Objective To estimate the prevalence of long COVID in children and adolescents and identify the full spectrum of signs and symptoms present after acute SARS-CoV-2 infection.

Overview: Independent investigators searched PubMed and Embase forobservational studies (a minimum of 30 patients ages ranged from 0 to 18) published before February 10th, 2022 meeting the definitions of the NIH (NICE) for long COVID-  consisting of both ongoing (4 to 12 weeks) and post-COVID-19 (≥12 weeks) symptoms. 

The literature search yielded 68 articles for long COVID in children and adolescents. After screening, 21 studies met the inclusion criteria and were included in the systematic review and meta-analyses.  A total of 80,071 children and adolescents with COVID-19 were included.  The prevalence of long COVID was 25.24% (95% CI 18.17-33.02), 

Click to enlarge
courtesy of Dr. S. Villapol

The most prevalent clinical manifestations were:
 
mood symptoms (16.50%; 95% CI 7.37-28.15),
 
fatigue (9.66%; 95% CI 4.45-16.46), and
 
sleep disorders (8.42%; 95% CI 3.41-15.20). 

When compared to controls, children infected by SARS-CoV-2 had a higher risk of persistent
- dyspnea (OR 2.69 95%CI 2.30-3.14),
 
- anosmia/ageusia (OR 10.68, 95%CI 2.48, 46.03), and/or
- fever (OR 2.23, 95%CI 1.22-4.07). 

The main limitation of these meta-analyses is the probability of bias, which includes lack of standardized definitions, recall, selection, misclassification, nonresponse and/or loss of follow-up, and the high level of heterogeneity.



SOURCE: https://www.medrxiv.org/content/10.1101/2022.03.10.22272237v1.full.pdf+html

Copyright: The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.





LONG HAUL META-ANALYSIS

Dr. Villapol is the Assistant Professor of Neurosurgery at the Center for Neuroregeneration in the Houston Methodist Research Institute.  She is also an asst. professor at Weill Cornell Medicine. Her commitments include the pursuit of novel neurorestorative treatments for debilitating brain injuries to open the door to alternative therapies that repair and recovery in the damaged brain through the periphery.   Her areas of research expertise includes studies in: Stroke, Inflammation, Microbiome, Immune activation, Cerebral blood flow (CBF), Traumatic brain injury (TBI), Microglia, Ischemia and Apoptosis. 

Diagram (R)- Courtesy of Dr. Villapol is the comprehensive diagram illustrating over 50 Long Term Effects of Covid-19, indicating collected metadata about specific disorders (percentile of all cases)

We connected with Dr. Villapol on the topic of Post-Covid/Long Haul symptoms or POST-ACUTE SEQUELAE (PASC).  Her profound contributions to the research project: "More than 50 long-term effects of COVID-19: a systematic review and meta-analysis" where she and other top international clinical minds have collaborated on the study of COVID-19 and its persistence, sequelae, and other medical complications that last weeks to months after initial recovery. This systematic review and meta-analysis aimed to identify studies assessing the long-term effects of COVID-19.  The paper provided comprehensive analysis of all recorded symptoms, signs, or abnormal clinical parameters persisting two or more weeks after COVID-19 onset that do not return to a healthy baseline can potentially be considered long-term effects of the disease. The studies classified in the meta-analysis included those published in the year 2020 (strictly before January 1st, 2021).






THE LATEST ON POST COVID CONDITIONS
Source: CDC.GOV 1/10/2022


Medical analysts, virologists and diagnostic experts assess this to be a LINGERING of health problems even after the acute phase of the illness.[1] Where most patients who survive Covid-19 cases after one to two weeks, those who show this issue test negative for the virus but feel unusual health symptoms.  A deeper study on post-Covid issues have identified two separate categories of health problems, one being categorized as LONG HAULERS (viewed as a continuance or a 2nd phase of the Covid infection) and more prominent health problems called POST-ACUTE SEQUELAE (PASC)

According to the CDC 2022 study, post-Covid issues, otherwise listed as "Long COVID" is a range of symptoms that can last weeks or months after first being infected with the virus that causes COVID-19 or can appear weeks after infection. Long COVID can happen to anyone who has had COVID-19, even if the illness was mild, or they had no symptoms. People with long COVID report experiencing different combinations of the following symptoms[3]:

- Difficulty breathing or shortness of breath
- Tiredness or fatigue
- Symptoms that get worse after physical or mental activities (also known as post-exertional malaise)
- Difficulty thinking or concentrating (sometimes referred to as “brain fog”)
- Cough
- Chest or stomach pain
- Headache
- Fast-beating or pounding heart (also known as heart palpitations)
- Joint or muscle pain
- Pins-and-needles feeling
- Diarrhea
- Sleep problems
- Fever
- Dizziness on standing (lightheadedness)
- Rash
- Mood changes
- Change in smell or taste
- Changes in menstrual period cycles

In addition, a recent study of young, healthy adult healthcare workers (in Sweden) adds new data to the  frequency of this Long COVID Syndrome- showing an est. 1 in 10 healthcare workers who had what at  originally appeared as mild symptoms of COVID-19 continued to experience one or more moderate to severe symptoms eight months later- including loss of smell and taste, fatigue, and breathing problems.  This negatively affected their work and personal lives.

SEQUELAE
Recent reports also show more prominent effects to vital organs, which can include damage to the lungs heart and brain. Reports have indicated that SARS-CoV-2 can invade, then inflame the heart muscle (called myocarditis), affecting the special balance between oxygen supply and distribution. This inflammation raises the risk of heart attacks as a result of increased blood clotting. In addition, the immune system reacting to Covid infections are known to cause a 'cytokine storm' which aligns with damage to major organs including the heart and lungs. [4]


EXPANDING POST-COVID DIAGNOSTICS: ENTER THE ULTRASOUND
By: Dr. Robert L. Bard, Radiologist

SCAN FOR HEART DISORDERS & DAMAGE
“Part of our chest scan for Covid-19 and post-covid issues is using an ultrasound to scan the heart- starting from the bottom of the lungs underneath the right and left rib cage. In the case of this image (L), an abnormal pulsation leads the investigation of the aortic valve with the spectral Doppler, only to show an abnormal doppler flow color pattern (yellow and teal) in the aortic valve indicating inflammation causing thickening of the valve, producing narrowing, then stenosis and turbulence. Once you find a cardiac abnormality, it could be related to Thromboemboli from the lower extremities or from the inferior vena cava that (in Covid cases) may show clots. These revelations lead to other confirmatory tests such as pet CT, pulmonary ventilation, and perfusion scans and perhaps MRI.” Also see feature "MEDTECH REVIEW: TRANSCRANIAL DOPPLER ULTRASOUND"


BLUE TOES and fingers are a newly recognized feature of microemboli from Covid-19. The growing population of patients with hyper coagulable comorbidities or exposure to the viral pandemic make the risk of increased thrombosis a real consideration when initiating cosmetic treatments. High resolution Doppler sonography documents altered vascular flow and images dermal and subdermal lesions such as cysts, cancers and inflammatory disorders that may be associated with discolored areas.  Risk of blindness from filler procedures has been documented worldwide for ten years from intravenous or intra-arterial injection. Foreign bodies (old or new fillers) may dislodge and produce vascular compromise at a distance from the point of entry. Preoperative vessel and facial nerve mapping with 4D image reconstruction is used to guide needle placement in certain situations. Advanced vascular imaging (30-100 mhZ sonography units, 3D/4D Doppler, RCM, OCT) may be useful in differential diagnosis of embolic phenomenon. Image guided treatment with Doppler assistance can reopen occluded vessels in a timely manner.

TEMPORAL ARTERITIS- “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.”


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 [6,7]. 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.



 

ULTRASOUND B-LINES (by: Dr. Pierre Kory- FLCCC.net)

“When conducting lung ultrasound scanning, you look for signs of B-LINES. The more B lines you have equals a bad lung ultrasound score – indicating a high risk of deterioration. For any treatment protocol, if a patient whose lung ultrasound scan was getting worse, we might want to start escalating therapy.” 



FEATURE: POST COVID DIAGNOSTICS
By: Dr. Bruce Patterson, Virologist (from 6/2021 interview)

My lab (IncellDx) has worked with over 5,000 treated and diagnosed long haulers now (which I think is probably the biggest cohort in the world) and growing at the rate of about a hundred patients a day from different regions, we can actually discern these symptoms more effectively.  For instance, they all talk about chest pain, but it's not really coming from their lung parenchyma. It's coming from the pleural cavity and the pleura and probably even the diaphragm, which contained inflammation. So when they take a deep breath, it hurts, but their pulse ox shows that they're 98% oxygen. So it has nothing to do with lung. 


We just published a report that "Long Haulerism" is really Endotheliitis and Vasculitis. And, we have marker CD40 Ligand and VEGF (Vascular Endothelial Growth Factor) -- they're elevated in almost every long-hauler because we found this cell that carries COVID protein 13-15 months after their infection. This cell is attracted to the blood vessels who have pathway involving FRACTALKINE (which is a protein most people may have never heard of). The cells express the Fractalkine receptors, so they migrate and patrol blood vessels all the while, bringing in COVID protein which elicits an active (local) immune response wherever the cells go - and they go everywhere. They cross the blood-brain barrier, they get into the pleural cavities, they get into the pericardium (the membrane that lines the heart) and people are talking about Pericarditis symptoms except they don't have the fluid that you normally see in a viral pericarditis. 

So to me, we found the all encompassing theme. But the presentation of Long Haulers analysis is entirely different on a patient by patient basis. And the other thing is these cells are mobilized by exercise and to a person every long holler has exercise intolerance. Some of the leading health centers in the country promote their approach to long haulers is to do physical therapy. As someone who tracks this on a cellular basis, PT is equivalent to "throwing gasoline on them and lighting it" because that's what you're doing.  

IMAGING: A COMPLETE VALIDATION
The diagnostic community (including my group) is so far ahead... we started looking at long haulers since June of 2020. We're treating it, we know what's causing it and that's why we're expanding globally.  To combine it with the imaging where you can visually see where we correct the immune system by what we do, being able to see that in a holistic, full body way and how that relates to resolution of symptoms is absolutely perfect. I mean, that's what you want to know.  In other words, physicians can survey the patient by asking if these symptoms are resolving... or is the brain fog resolving, or the tinnitus fading in three days of therapy with Maraviroc- therapeutically, we have the means of addressing the symptoms, but then to have the confirmation from medical imaging is extremely reassuring to everybody, including the patients.




ORIGINAL REPORT:
(Update from report published 6/3/2021)- Over a year since the Coronavirus surge made New York the Epicenter of the U.S. pandemic, our domestic protocols are now showing a steady turn of the tides in cases, infections and ICU capacity. Current readings from CovidActNow.org indicate 168,489,729 people (51% of the U.S. population) have received at least one dose of the vaccine and a US map that once showed most of the states as DEEP RED, showing the highest percentages of severe risks are now YELLOW, second from the Green, or LOW RISK.

Though medical and news reports indicate that the vast majority of recovered patients do not appear to show any further health issues, Prevention101 reviews the recorded cases of POST-COVID DISORDERS from those who have identified similar patterns of symptoms. In this special issue, we have assembled a group of experts from varying medical disciplines whose clinical experiences identify and define the after-effects of Covid infection.



COVID ACT NOW: 2021 MAP:

REFERENCES


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