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Hi Misiu,
You are most welcome and I am very happy for you and wish your son a speedy recovery!
This is great and appreciated. Thank you.
From the paper you shared: Serum for PK analysis was taken at 0h (pre-dose), 0.5h, 1h, 3h, 6h, 24h, 32h, 48h, 56h and 96h post-treatment during the first week and then on Days 8, 12, 15, 22, 29 and 59 and Figure 2. plots out the serum concentration over time: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2856743/figure/F2/
From the information that has been shared, an earlier response is not unreasonable and more importantly I am very happy for misiu and her son.
Agreed. Rapid acting insulin has an onset of 30 minutes. SubQ morphine I have always thought to be a bit longer but still reasonably quick.
There are papers that have looked at the pharmacokinetics of Leronlimab for HIV such as the link below. This study did an iv infusion to then measure serum concentration of Leronlimab.
Would anyone be aware of similar studies using SubQ injections?
https://www.researchgate.net/figure/PRO-140-pharmacokinetics-and-relationship-with-antiviral-effects-A-Mean-serum_fig3_23237531
Agreed!
There is a great deal to learn. Hopefully the momentum will start to build.
I am awaiting the release of the data from the longhaulers study and would like to see how it fits with the “Long Hauler Score” outlined in Dr. Patterson's paper: S1 = (IFN-? + IL-2 ) / CCL4-MIP-1ß and their subsequent responses to the 24 symptoms reported.
I have enjoyed reading your posts and am sharing this link should it be of interest. COVID-19 and acute pancreatitis: examining the causality - https://www.nature.com/articles/s41575-020-00389-y
If nothing else, it provides a nice overview of the potential for COVID-19 to infect the pancreas.
While they shared the breakdown (severe, moderate, mild, none) for some of the symptoms of interest; it would have been useful for a similar breakdown of diarrhea and its severity. Hopefully, when the data have been reviewed further, this too will me made available.
GLTA
Thank you. This is a nice paper. Have a great weekend.
Good morning,
There is a CytoDyn poster accessible at: https://d1io3yog0oux5.cloudfront.net/_809f9420834a1b994cd93f6681bcc0e3/cytodyn/db/193/2945/pdf/CytoDyn+Poster+Presentation+at+CROI+2019+%28March+7%2C+2019%29.pdf
If you look at Figure 3. Antiviral Activity of Short-Term Monotherapy with PRO 140 - the response curves for dosing would support the 50 hour period.
If interested, this is the poster Dr. Pourhassan has to his right shoulder in the Proactive videos -https://d1io3yog0oux5.cloudfront.net/_809f9420834a1b994cd93f6681bcc0e3/cytodyn/db/193/2464/pdf/CytoDyn+-+ASM+2019+Poster+Presentation+re+CD02_Final.pdf that can be seen here -
I would agree with you.
Things do not look good.
Many of the crucial ICU staff have not had a break and ICU beds will likely be limited due to a lack of providers.
The system capacity is coming under increasing amounts of stress with discussions around triage and who will and will not be put on life support.
https://www.cbc.ca/news/health/covid-ontario-icu-triage-1.5992188
Canada is not a Hail Mary for Cytodyn rather Leronlimab is likely a potential Hail Mary for Canada.....
the numbers are becoming increasingly grim
#COVID19 Hospital/ICU in #Ontario Hospital
Hospitalizations non-ICU: 1447
ICU non-ventilated: 239
ICU+ventilator: 516 (Total ICU Capacity ~2500 beds (unclear if providers to staff them)
= Total hospitalized: 2202
Sourced from -
#COVID19 Hospital/ICU in #Ontario 🏥
— Dr. Jennifer Kwan (@jkwan_md) April 19, 2021
Hospitalizations non-ICU: 1447
ICU non-ventilated: 239
ICU+ventilator: 516
= Total hospitalized: 2202
Hospital #'s incomplete on holidays/weekends.#COVIDー19 #COVID19Ontario #onpoli pic.twitter.com/XYgfObtRT3
Hi,
Your numbers for Ontario do not seem right.
For APR 16: #COVID19 in #Ontario
4812 cases*, 25 deaths, 3151 resolved
64304 tests/day, 38815 pending, 8.2% pos
1955 hospitalized (701 in ICU)
ICU total: 701
ICU non-ventilated: 221
ICU+ventilator: 480
Are you able to share where the ECMO number came from?
ECMO Machines - see link below - are not that accessible and I am interested to learn the total number in Ontario, Canada as things are projected to deteriorate further.
'High level' of demand
Roughly 40 Canadian hospitals have access to at least one ECMO machine, representing just three per cent of all hospital sites across Canada — though it's unclear how many machines in total the country has access to.
https://www.cbc.ca/news/canada/toronto/demand-covid-19-treatment-ontario-1.5816276
Agreed.
24% is a big number when you compare it to some of the benefits adjuvant cancer therapies provide - http://www.lifemath.net/cancer/breastcancer/therapy/
While Leronlimab and systemic therapies for breast and other cancers both improve survival, there is no comparison with regards to their toxicities.
The 2005 study in the NEJM for adjuvant herceptin had a similar survival benefit (33% reduction in the risk of death) with a much larger sample size (n=2000+).
So to go back to the original question, yes every year thousands of women who are HER2/neu +ve are offered a treatment which has a 33% benefit. Unlike Leronlimab, Herceptin unfortunately has more reported side effects ( https://www.webmd.com/drugs/2/drug-16621/herceptin-intravenous/details/list-sideeffects ).
Agreed.
You need to consider the potential for benefit and the potential for harm. A 25 to 33% increase in cure/control/prevention from disease progression/reduction in the risk of death against a negligible risk of side effects/toxicities is meaningful.
We make decisions like this everyday. A therapeutic agent that provides 24% risk reduction for mortality, with no significant side effects, and no restriction on other therapies would be a reasonable intervention to offer.
From an administrative perspective, an agent that facilitates patients transition out of hospital, alive, would help to open up capacity for elective surgeries and other activities that have been paused or curtailed during the pandemic.
All IMHO too.
Good luck to all and to those who would benefit from this.
Dr. Kelly on CBSNLive at 1pm today......
https://twitter.com/cytodyn/status/1342152597285703680?s=21
CytoDyn on Twitter
TWITTER.COM
CytoDyn on Twitter
“Our CMO, Dr. Scott Kelly, will be on @CBSNLive today in the 1pm ET hour, talking about the important work we're doing to combat the long-term symptoms of COVID-19.”
Here is hoping to happy holidays for all!
You are welcome. I have appreciated your posts and hope this is a small way for me to contribute to this forum.
You are most welcome!
I hope it is of use to you.
Good morning,
I am sharing this should it be of help to anyone. Page 6 outlines a regimen for Prophylaxis.
https://www.evms.edu/media/evms_public/departments/internal_medicine/EVMS_Critical_Care_COVID-19_Protocol.pdf
Regards.
GLTU/GLTA
Thanks I have read it twice now! Am curious where it was submitted before it was finally accepted. It only took this journal two weeks to receive it, accept the revisions and then release it.
I thought there were at least three more: 2 EIND papers and The Mild to Moderate paper.
Agreed. The HHS data that were leaked confirm the rapid rate of increase and predict the capacity of the system to provide care will become a challenge as demand outstrips the ability to provide care. One would hope that accrual accelerates to help and that the trial in its entirety is fully enrolled before the end of the year if not halted at the 75% analysis.
https://assets.documentcloud.org/documents/7278119/HHS-Daily-COVID-Hospitalizations-Summary-Report.pdf
https://assets.documentcloud.org/documents/7278119/HHS-Daily-COVID-Hospitalizations-Summary-Report.pdf
With the increasing rate of increase in new cases, things are very likely to deteriorate. For the HHS Report in the link above, the data appear to show a correlation between COVID Inpatients and the percentage of COVID Inpatients Ventilated.
It is not immediately clear to me that the vaccine will change the near to intermediate term progression. What impact it has on the demand for medical care and ventilators over the longer term is also unknown.
Bruce Patterson tweeted out today a presentation next Wednesday on TrialSite News. Will be speaking about CCR5 and long-haulers. Should be interesting.......
Agreed -they need a strategic communication consultant and media help
Agree with you as does the published literature.
Donepezil for dementia due to Alzheimer's disease - PubMed
https://pubmed.ncbi.nlm.nih.gov/29923184/
Aricept is approved with the majority of studies being 6 months.
Why would this be any different for leronlimab?
Thanks
This one seems like a no brainer then!
Fulminant Hepatic Failure in Hepatitis A Infection - Is this an indication that has already been captured on the list?
Conclusion highlights significance of CCR5 antagonists.
https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.26557
RESEARCH ARTICLE
Prognostic, clinical and therapeutic importance of RANTES-CCR5 axis in hepatitis A infection: A multi-approach study
Vargab Baruah Diptika Tiwari Rajib Kishore Hazam Moumita Bose Dipankar Bujarbaruah Anjan Kumar Saikia Premashish Kar Sangit Dutta Sujoy Bose
First published: 25 September 2020
https://doi.org/10.1002/jmv.26557
Funding: : This research did not receive any specific grant from funding agencies in thepublic, commercial, or not-for-profit sectors.
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/jmv.26557
ABSTRACT
Fulminant hepatic failure (FHF) is a lethal manifestation of hepatitis A virus (HAV) infection, whose underlying mechanisms are poorly understood. We aimed to evaluate the importance of the modulation of RANTES-CCR5 signalling axis and its immunomodulatory effects in directing hepatitis A disease pathogenesis using an in-silico, in-vitro and patient cohort based approach.In-silico interaction studies were performed using computation approaches with suitable software. Differential expression of relevant cytokines and immune cell markers were studied using qRT-PCR, ELISA and flow-cytometry-based methods. In HepG2 cell line, we studied inflammatory responses and susceptibility to HAV infection following RANTES stimulation and antibody blockade of CCR5.The HAV-VP3 region exhibited high interaction in CCR5: HAV complexes. RANTES levels were significantly increased in FHF cases. A reduced monocyte and T-cell activation was observed in FHF cases. RANTES expression inversely correlated with viremia but positively correlated with pro-inflammatory responses. Hyper Th1-biased immune responses, marked by high IL-12/IL-10 ratio were observed in FHF cases, which were also characterized by upregulated TNF-a expression and reduced IFN-? expression. In-vitro, RANTES was protective against HAV infection, but resulted in upregulated TNF-a expression. Although viral load increased upon regulation of inflammatory responses by CCR5 blocking, it was still significantly lower compared to control HAV-infected cells.
Our study suggests the importance of RANTES-CCR5 signalling and linked-immunomodulation in HAV disease pathogenesis, as well as highlights the utility of CCR5 antagonists as a risk-reduction strategy in FHF patients.
Our findings therefore have important implications for the management of high-risk HAV infections.
This article is protected by copyright. All rights reserved.
Agreed. It will also significantly raise the profile in both the academic and clinical communities. This seems to be one of the current weaknesses of our present state. As more and more areas see rising local case counts, it would be great to have leronlimab on the radar of key policy and decision makers.
Manuscripts - from the call last night, three manuscripts were mentioned. It was said on the call that all of the manuscripts have been submitted and would be for the EIND patients. With Bruce Patterson’s manuscript, there will be a total of four. Are there any other papers still to come and is there a reason why the three EIND papers have not been made available like Bruce Patterson’s was?
Having published peer reviewed data will help and it would be useful to know when this will happen.
A. and nothing but Option A.
Respectfully, I would consider Leronlimab in someone who is mild to moderate with risks factors such as: advanced age, hypertension, diabetes, obesity and possibly male gender. With the data that are available from the start of the pandemic, it would be a reasonable modelling exercise to calculate the number needed to treat and do a simple cost-utility analysis.
Agree with you that in the absence of other factors, it may not be needed in MM.
One could propose to monitor NEWS2 and develop and algorithm to determine if Leronlimab is needed.
All IMO
Both. I don’t see the plasma as providing benefit and inferred she was randomized to Leronlimab based on her discharge home in a week after presenting with an O2 sat of 70% on room air.
The focus of the article seems to be on plasma. Would be great for the reporter to do one on Leronlimab.
Local media in Houston, Leronlimab appears 2/3rds into the article......
https://www.houstonchronicle.com/lifestyle/renew-houston/health/article/plasma-covid-ut-health-texas-cure-expert-doctor-tx-15528307.php
It would be great to have the 595,595,595th share that CytoDn issues framed for posterity.
Yes for the healthy controls.
The history tab on the link has this as the paper from May. Thanks. It is not clear if this is the version that contains his revisions submitted in response to the reviewers comments?
A bargain at twice the price.
Does anyone have the pre- print with the COVID +be control group Dr. Patterson referenced on Dr. Drew?
I agree with you 595 times
It has effectively blocked the introduction and testing of other potential therapeutics. Aside from this, there are no other real data.
If it helps, here is a summary and link to the PDF......the Meaning Section is important to highlight- uncertain clinical significance.
Question Does remdesivir provide a benefit on clinical status for patients hospitalized with moderate coronavirus disease 2019 (COVID-19) pneumonia?
Findings In this randomized, open-label, phase 3 trial that included 584 patients with moderate COVID-19, the day 11 clinical status distribution measured on a 7-point ordinal scale was significantly better for those randomized to a 5-day course of remdesivir (median length of treatment, 5 days) compared with those randomized to standard care. The difference for those randomized to a 10-day course (median length of treatment, 6 days) compared with standard care was not significantly different.
Meaning Hospitalized patients with moderate COVID-19 randomized to a 5-day course of remdesivir had a statistically significantly better clinical status compared with those randomized to standard care at 11 days after initiation of treatment, but the difference was of uncertain clinical importance.
https://jamanetwork.com/journals/jama/fullarticle/2769871