Saturday, September 12, 2020

HOW AN INTENSIVIST HANDLES COVID CARE?


"Arguably, most doctors are not like us... we are the last line with the dying and (those with) the most severe illnesses. We are conditioned to work creatively and more aggressively under very limited time to reverse life threatening disorders."

From the Editor:

Having a front row seat to the inner workings of some of the top medical professionals in action is 
a great privilege that we as reporters enjoy when conducting interviews for Prevention101.  We report on chronic disease specialists who harness leadership through their own unique and even bold approach to returning their patients back to wellness. 

This unique feature covers two INTENSIVE CARE professionals; Dr. Pierre Kory and Dr. Young Lee- both active responders of the New York covid spike in early March of this year.  Dr. Kory (from Madison, Wisconsin) is a Pulmonologist, an ICU Covid Care Specialist and a medical researcher in advanced treatments of infectious diseases.  He is a recent transplant from NYC who found himself racing back into the exhausted front lines of Beth Israel Hospital at the height of the New York pandemic. 

- he was a program director for the fellowship program of pulmonary critical care. 

On the receiving end is Dr. Lee- at New York's Beth Israel Hospital (a branch of Mt. Sinai Health system).  
Yes. So dr. Corian us, we have a very long history. So my hospital is Mount Sinai, Beth Israel, which is like a branch hospital in this Mount Sinai system. We have a four Mount Sinai hospital in Manhattan, so we are one of them. Um, dr. Corey was actually with us, um, I will say five, six years ago. And before he left to Wisconsin, he was a program director for the fellowship program of pulmonary critical care at Mount Sinai, Beth Israel. Um, so we are struggling for sure. So Mount Sinai, Beth Israel, typically we have a 16 bed medical ICU, um, and typical, they have like, they like today we have 12 patients.

Dr. Kory details the unique personality of an intensivist, seeking out the highest hit areas in the country while sharing his views on the 

use of steroids to manage and treat CoronaVirus patients and explores his many findings about "what works vs. what works BEST" according to his experiences with patient response in the ICU.

Interview with an ICU Critical Care Physician



Monday, August 31, 2020

From the Experts: HOSPITAL COVID INFECTION PREVENTION

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

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.


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.


VIEWPOINTS

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.




Other recent articles from:



FUCOIDAN: Anti-Cancer Functions + Inhibitor of Covid-19
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."


MODERN OPTICS To Prove Masking Benefits & Infection Control  LaVision imaging technique shows how masks restrict the spread of exhaled air.  The primary way of person-to-person corona virus transmission is via aerosols or small droplets created by breathing, sneezing or coughing. The reach of exhaled air can be effectively reduced using a face mask as shown in the video. A simple Schlieren imaging technique is applied to visualize the air flow caused by a person breathing and coughing. Using a face mask the exhaled air flow is blocked reducing effectively the risk of infection.


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".




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Monday, August 24, 2020

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]



EPILOGUE: 

BEDSIDE VALIDATION 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 validation technology 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/)



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




Other recent articles from:




"Does UV-C Carry the Promise of SAFE SANITIZING?" - July 22, 2020 - In our current health crisis, prevention terms like DISINFECTING, SANITIZING or ANTI-BACTERIAL treatments are part of our common reality. Historical tests of UVC light were performed by irradiating surfaces with bacteria. Modern developments have honed the science of deactivating viruses and their ability to transmit diseases when directly applying 222-254 nm of UVC light on airborne viruses and microbes. (See article)


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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Tuesday, August 18, 2020

FUCOIDAN: Anti-Cancer Functions + Inhibitor of Covid-19

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 (including Undaria pinnatifida and Cladosiphon okamuranus Tokida).... 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."

In addition to its anticancer & anti-tumor components, Fucoidan has also shown effects as an antioxidant, anti-angiogenic, antiviral, and anticoagulant activities. [5]  These properties have captured the current interest of clinicians determined to produce treatment solutions for the complex symptoms of the CoronaVirus.  At the advent of public recognition of the drug REMDESEVIR (a widely popularized drug for its qualities as an immunomodulator), recent news headlines are highlighting major comparisons and competing statements with "the Seaweed extract to out-perform Remdesivir as a Covid inhibitor".  Also, Fucoidan has been compared to HEPARIN, an anticoagulant for its chemical composition of sulfated polysaccharide.

REMDESIVIR: Is recognized as the first approved drug to be effective against SARS-CoV-2. [8]
In a clinical study (on 8/6/2020) by The National Institute of Allergy and Infectious Diseases (NIAID)- a branch of the NIHtests for the efficacy of the antiviral Remdesivir + the interferon Beta-1a is underway a potential COVID-19 treatment.  "Laboratory studies suggest... type 1 interferon can inhibit SARS-CoV-2 and two closely related viruses, SARS-CoV and MERS-CoV. In addition, two small randomized controlled trials suggest that treatment with interferon beta may benefit patients with COVID-19." [6]

First isolated by Dr. Harvey Kylin in 1913 (Uppsala University, Swden), Fucoidan has been known to come from different species of brown algae and seaweed, carrying different biochemical properties[0] Fucoidan's bioactivity has been linked to its anti-cancer properties including the induction of inflammation through the immune system, oxidative stress and stem cell mobilization[1].

The anti-cancer property of fucoidan has been demonstrated in vivo and in vitro in different types of cancers. For the Immune System, Fucoidan has been recognized to increase the number of natural killer cells and increase in the number of cytotoxic T-cells. Tests/Trials of fucoidan's effects on dendritic cells showed that the stimulation of CTLs was more effective in fucoidan-treated DCs which exerted a high level of specific lysis of breast cancer cells [2]. In addition, Fucoidan has also been known to carry (immunomodulatory) protective effects against the side effects from chemotherapies or radiation.

Geographical distribution of Okinawa mozuku.
Anti-inflammation
Inflammation and immunity play important roles in the development of tumorigenesis [7]. Current epidemiological and preclinical results strongly support an anti-inflammatory approach to treating cancers. Several therapeutic agents targeting cancer-derived inflammatory responses and related signaling molecules, cytokines, transcription factors, and immune cells are being developed and tested [7.5]. Inflammation, cancer recurrence and cancer metastasis have a complicated relationship. Inflammatory responses play important roles in tumor development, including metastasis [9].

In mid-2018, an oral administration and absorption study of Mozuku fucoidan in 396 Japanese volunteers was performed. [10]. The results showed that fucoidan absorption in humans is extremely low; the fucoidan concentration after oral administration was approximately ten times higher in urine than in serum, confirming the intestinal absorption of Mozuku fucoidan in humans. The results indicated that volunteers living in Okinawa prefecture have the maximum value of urinary fucoidan, significantly higher estimated urinary excretion of fucoidan by place of residence, and significantly higher Mozuku fucoidan consumption habits compared with those living outside Okinawa prefecture. However, the biological mechanisms of fucoidan absorption across the intestinal tract need to be further investigated.







FROM THE SOURCE

This section is directly sourced from an interview with Dr. Yoshiyuki Miyazaki at the NPO Research Institute of Fucoidan in Fukuota, Japan.







FUCOIDAN AND THE IMMUNE SYSTEM
Fucoidan is extracted using a special filtration membrane, and components with a molecular weight of 10,000 or less (impurities such as salts, heavy metals) are removed during the extraction process. As in the case of a research program from Keio University, synthesis of Fucoidan [1][2][3], is possible at the laboratory level, but has not yet been put to practical use.

We emphasize that the actual physiological action of Fucoidan is not "anti-cancer" that suppresses the growth of cancer cells with direct interaction, but "immune improvement" that is a host defense mechanism to prevent tumor growth. It is believed that Fucoidan activates the human body's natural immune mechanism that leads to the treatment of diseases that progress with a measurable decrease in immunity. I have studied on the mechanism of immune regulation by Fucoidan since 2010 as chief researcher in NPO Research Institute of Fucoidan, and now continuing in Laboratory of Bioactive Polysaccharide Analysis, Faculty of Agriculture in Kyushu University (2016. 4 - present, associate professor). Through 10 years of research, I have found unique and certain immuno-potentiating effects of Fucoidan. I hope that immune enhancement by Fucoidan may enhance the host resistance against SARS-CoV-2 and vaccine efficacy for Covid-19 treatment.

Fucoidan is not classified as a drug, therefore is not currently applied as a measurable treatment solution for the pandemic. (Development of vaccines for COVID-19 is desired to improve the current situation.) Fucoidan may, however be used as an effective supplement to immune enhancement in the vaccination.

EFFICACY & GLOBAL ACCEPTANCE
Some human trials have revealed useful physiological effects of Fucoidan improving medical treatment. However, in my opinion, there remains varied challenges in pharmaceutical approval of Fucoidan (due to the reasons described above)  unless mass-production of synthetic Fucoidan would be developed. Meanwhile, laboratory studies indicated success in synthesizing Fucoidan at the Keio University research program-- whereby the effects of oligofucosides, synthetic sulfated oligosaccharide with backbone structures of Fucoidan have been investigated on cancer cell growth [1][2] and influenza virus infection [3].

Currently, the scientific and medical communities have no conclusive evidence of therapeutic effects of Fucoidan on SARS-CoV-2. However, Fucoidan has been known to prevent dengue virus infection by direct interaction with viral envelope glycoprotein[4]. Furthermore, it was reported that Fucoidan possibly control influenza virus infection by augment immune responses, especially virus neutralizing antibody production[5]. In this context, we previously reported that Fucoidan derived from Undaria pinnatifida augmented immunoglobulin (IgA, IgG and IgM) production by mouse spleen lymphocytes[6]. So, we are believing that Fucoidan have sure physiological activities to reinforce vaccine efficacy.

ACTIVE COMPONENTS
Fucoidan is a natural ingredient with complex composition- whereby its pharmacological component is not a single chemical substance like a DRUG or MEDICINE. Fucoidan is a kind of polysaccharide, but similar polysaccharides have β-glucan derived from mushrooms (compounded in Umi-no-Shizuku). A purified β-glucan preparation named "Lentinan" has uniform composition and is approved as a drug for gastric cancer in Japan. In contrast, "Fucoidan" cannot be expected to have medicinal action by single component like β-glucan, so it is used as a naturally occurring SUPPLEMENT like Kampo rather than pharmaceuticals.

The source plant of Fucoidan is not only Undaria pinnatifida but also Cladosiphon okamuranus Tokida-  the most major species of Mozuku Fucoidan (Okinawa mozuku in Japanese name).
Physiological properties of Fucoidan has had extensive presence in the health and wellness communities, where scientific information is accessible in many articles- including Therapies from Fucoidan; Multifunctional Marine Polymers[7]   A protective effect of Fucoidan against side effects from chemotherapy with FOLFOX or FOLFIRI has been investigated in the following report; Fucoidan reduces the toxicities of chemotherapy for patients with unresectable advanced or recurrent colorectal cancer[8]


GEORGRAPHIC SOURCING
I believe Fucoidan is related to brown algae habitat and food culture. In Japan, it can be seen that seaweed has been used for health since ancient times, since there is a description in "本草和名:Honzo Wamyo", the oldest existing drug dictionary in Japan compiled around the year 900 AD. In Japan, where the country faces the sea, a food culture that incorporates seafood into the diet takes root, and it is thought that aquaculture of seaweeds and the research have advanced.

Seaweeds are classified into three groups, "red algae", "green algae" and "brown algae", and Fucoidan is a component contained only in brown algae. Other plants do not have Fucoidan.
Among the brown algae, only Fucoidan contained in Mozuku (Cladosiphon okamuranus Tokida), Mekabu (Undaria pinnatifida), and Gagomecomb (Kjellmaniella crassifolia) has the Japan Health Food Authorization (JHFA)[9] quality standards and can be certified as conforming.  The association conducts work that contributes to the health promotion of the Japanese nationals, such as collecting and spreading information on food with health claims and operating JHFA and other certifications.

According to reports, response of Fucoidan appears to affect a higher rate of residents of the sourced area (Japan) than any other part of the globe.  The research team at "Station Biologique de Roscoff", research and educational institute for marine biology and oceanography in France, reported that Japanese can decompose some kinds of polysaccharides contained in seaweed, because their enterobacteria (Bacteroides plebeius) took up gene for degrading enzyme from other marine microorganisms (published in British scientific journal "Nature" at April 8, 2010). Even within Japan, there are regional differences as with food culture, so I believe it is highly possible that there will be regional differences in the effects of Fucoidan around the world.





References:
1) Systematic synthesis of sulfated oligofucosides and their effect on breast cancer MCF-7 cells (https://pubs.rsc.org/en/content/articlehtml/2014/cc/c4cc03544e)
2) Systematic synthesis of low-molecular weight Fucoidan derivatives and their effect on cancer cells (https://pubs.rsc.org/en/content/articlehtml/2015/ob/c5ob01634g)
3) Novel hemagglutinin-binding sulfated oligofucosides and their effect on influenza virus infection (https://pubs.rsc.org/en/content/articlehtml/2018/cc/c8cc03865a)
4) Structure and anti-dengue virus activity of sulfated polysaccharide from a marine alga (https://www.sciencedirect.com/science/article/pii/S0006291X08016562)
5) Supplementation of Elderly Japanese Men and Women with Fucoidan from Seaweed Increases Immune Responses to Seasonal Influenza Vaccination (https://academic.oup.com/jn/article/143/11/1794/4637681)
6) The enhancing effect of Fucoidan derived from Undaria pinnatifida on immunoglobulin production by mouse spleen lymphocytes
(https://www.tandfonline.com/doi/full/10.1080/09168451.2014.930323)
7) "Therapies from Fucoidan; Multifunctional Marine Polymers"
https://www.mdpi.com/1660-3397/9/10/1731/htm
8) Fucoidan reduces the toxicities of chemotherapy for patients with unresectable advanced or recurrent colorectal cancer  https://www.spandidos-publications.com/10.3892/ol.2011.254
9) JHFA is a certificate given to health foods that comply with voluntary food standard set by the Japan Health and Nutrition Food Association (JHNFA). JHNFA is a public interest incorporated foundation authorized by the Cabinet Office with the aim of promoting public health (http://www.jhnfa.org/english-info.html).





The above results show that fucoidan, whether through basic in vitro to in vivo research studies or clinical trials in humans, has been proven to produce effect of adjuvant therapy on cancer treatment. This allows molecular mechanisms in cancer research to be applied in adjuvant treatment, in line with the pursuit of translational medicine and the mindset of establishing a direct link between basic medical research and clinical application.

In conclusion, understanding the mechanisms underlying the anti-cancer effects of fucoidan, the advantages of combining fucoidan with therapeutic agents in the treatment of cancers, and the pharmacological limitations of fucoidan will aid the development of more informed approaches to treating cancers and may improve current clinical outcomes for cancer patients.



References:
0. 4. Kylin H. Biochemistry of sea algae. HZ Physiol. Chem. 1913;83:171–197. doi: 10.1515/bchm2.1913.83.3.171. [CrossRef] [Google Scholar]

1. Kwak J.Y. Fucoidan as a marine anticancer agent in preclinical development. Mar. Drugs. 2014;12:851–870. doi: 10.3390/md12020851. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

2. Hu Y., Cheng S.C., Chan K.T., Ke Y., Xue B., Sin F.W., Zeng C., Xie Y. Fucoidin enhances dendritic cell-mediated t-cell cytotoxicity against ny-eso-1 expressing human cancer cells. Biochem. Biophys. Res. Commun. 2010;392:329–334. doi: 10.1016/j.bbrc.2010.01.018. [PubMed] [CrossRef] [Google Scholar]

Main sources:
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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4413214/

5. Fucoidan Extracted from Undaria pinnatifida: Source for Nutraceuticals/Functional Foods
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6164441/#B4-marinedrugs-16-00321

6. NIH clinical trial testing remdesivir plus interferon beta-1a for COVID-19 treatment begins
 https://www.nih.gov/news-events/news-releases/nih-clinical-trial-testing-remdesivir-plus-interferon-beta-1a-covid-19-treatment-begins

7. Albrengues J, Shields MA, Ng D, Park CG, Ambrico A, Poindexter ME, Upadhyay P, Uyeminami DL, Pommier A, Küttner V, Bružas E, Maiorino L, Bautista C, Carmona EM, Gimotty PA, Fearon DT, Chang K, Lyons SK, Pinkerton KE, Trotman LC, Goldberg MS, Yeh JT, Egeblad M (2018) Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice. Science 361:1314–1315

7.5 Grivennikov SI, Greten FR, Karin M (2010) Immunity, Inflammation, and Cancer. Cell 140(6):883–899

8. FDA: Frequently Asked Questions on the Emergency Use Authorization for Remdesivir for Certain Hospitalized COVID-19 Patients -  https://www.fda.gov/media/137574/download

9. SpringerOpen: https://clintransmed.springeropen.com/articles/10.1186/s40169-019-0234-9 (open access)

10. Kadena K, Tomori M, Iha M, Nagamine T (2018) Absorption study of mozuku fucoidan in japanese volunteers. Mar Drugs 16:254. https://doi.org/10.3390/md16080254

11. https://www.mdpi.com/1660-3397/16/8/254