Podcasts about cd4 cd8

In this episode, we sit down with Dr. John Lewis, a leading expert in nutritional research and the therapeutic potential of Aloe polysaccharides. Dr. Lewis shares insights from his groundbreaking studies on Alzheimer's disease, multiple sclerosis (MS), and the broader impacts of Aloe polysaccharides on immune function and brain health. Key Topics Discussed Understanding Aloe Polysaccharides What are Aloe polysaccharides? How are they extracted and formulated for nutritional supplements? Research on Alzheimer's Disease and Multiple Sclerosis Overview of Dr. Lewis's studies on Alzheimer's disease and MS. Impact of Aloe polysaccharides on cognitive function and disease progression. Immune System Modulation Effects of Aloe polysaccharides on CD4 to CD8 ratios. Regulation of key cytokines: TNF-alpha, VEGF, and BDNF. Balancing TH1 and TH2 responses. Brain Care Formulation Detailed discussion on the Brain Care formulation developed by Dr. Lewis. Clinical results and patient outcomes. Challenges in Nutritional Research Funding difficulties for nutritional and supplement research. Issues with the pharmacological model of placebo-controlled randomized double-blind trials. Why this model is challenging for evaluating supplements and nutritional interventions. Future Directions and Innovations Potential future applications of Aloe polysaccharides in other health conditions. Innovations in nutritional research methodologies. Key Takeaways Aloe Polysaccharides: Naturally occurring compounds with significant therapeutic potential, particularly in modulating immune function and supporting brain health. Clinical Research: Dr. Lewis's studies highlight the positive effects of Aloe polysaccharides on Alzheimer's disease, MS, and overall immune health. Nutritional Research Challenges: The current pharmacological model of clinical trials poses challenges for the study of supplements, necessitating new research approaches. Research References Studies on Alzheimer's disease and Aloe polysaccharides: Positive impacts on cognitive function and disease markers. Research on MS: Aloe polysaccharides and their role in managing symptoms and progression. Immune modulation: Detailed findings on CD4/CD8 ratios, cytokines (TNF-alpha, VEGF, BDNF), and TH1/TH2 balance. Dr. John Lewis provides compelling evidence on the health benefits of Aloe polysaccharides and underscores the need for innovative research methodologies in nutritional science. This episode offers valuable insights for anyone interested in the intersection of nutrition, immune function, and brain health.Connect with Dr. John Lewis Website: Dr. John Lewis Nutrition If you want to get Daily Brain Care visit our online curated range of cutting edge longevity and anti-aging supplements at  BIO John E. Lewis, Ph.D. is the Founder and President of Dr Lewis Nutrition™. Dr. John E. Lewis has spent most of his career developing a unique approach as someone who "walks the walk" through all of his combined professional and personal experiences to attaining optimal health through nutrition, dietary supplements, and exercise. Throughout his research career, he has evaluated many different nutritional approaches to enhancing well-being, particularly for brain health, immune function, and counteracting aging. He can separate fact from fiction regarding how to utilize nutrition and dietary supplements to help you achieve and maintain optimal health. If you need a trusted source of information, products, and services, then look no further than Dr. Lewis and how he can help you achieve your health-related goals. Professional Career Dr. Lewis is past full-time Associate Professor in the Department of Psychiatry and Behavioral Sciences at the University of Miami Miller School of Medicine and the Founder and President of Dr Lewis Nutrition™. He is a Diplomate, Faculty Member, and Advisor of the Medical Wellness Association. He has been the principal investigator of over 30 different studies on human health in his research career. During that time, he either directly raised or indirectly supported raising over $23 million in grants, gifts, and contracts for research studies and clinical trials and educational programs for medical students. In addition to his research, Dr. Lewis has been an invited national and international lecturer and guest speaker at conferences and as a guest on television shows. He is a well-known author with over 180 peer-reviewed publications in some of the world's leading scientific journals. He has also mentored many different students, from undergraduates to post-doctoral trainees, in not only how to conduct clinical research but to apply the principles of health promotion into daily practice. Research Interests Much of Dr. Lewis's research has focused on evaluating the effects of nutrition, dietary supplements, and exercise on various aspects of human health. He and his colleagues have been continually searching for ways to help people achieve and maintain health through natural treatments that align with our physiology. A primary stimulus for the origin of Dr Lewis Nutrition™ occurred after Dr. Lewis ran his landmark study on how an aloe polysaccharide multi-nutrient complex improved cognitive and immune functioning after 12 months in persons with moderate to severe Alzheimer's disease, leading to the creation of the dietary supplement, Daily Brain Care. Daily Brain Care showed clinically and statistically significant improvements in cognition according to the ADAS-cog cognition score and statistically significant improvements in inflammation (according to TNFα and VEGF), immune function (according to the CD4/CD8 ratio), and adult stem cells (according to CD14+ cells). His seminal publication from the study in the Journal of Alzheimer's Disease not only spurred him to leave academics and pursue a science-based business career, but also enabled him to be selected for a widely-acclaimed TEDxMiami talk. Founding Dr Lewis Nutrition™ While Dr. Lewis still maintains an academic affiliation, he chose to leave a full-time research career to pursue his true passion of helping people achieve health through nutrition, dietary supplements, and exercise. His research in brain health and immune function was key in the creation of Daily Brain Care, but afterward he chose to shift into business where the opportunity to reach a larger audience is greater. Dr Lewis Nutrition™ is the vehicle through which Dr. Lewis leverages his many years of personal and professional work to spread a message of health that is so desperately needed, particularly for those who are afflicted with an all-too-common chronic disease, e.g., neurodegeneration, immune dysfunction, or cardiac and metabolic disorder. Dr. Lewis will continue to be a thought leader to help people utilize the power of nutrition and dietary supplements and learn how to take control of and optimize their health.         Personalised Health Optimisation Consulting with Lisa Tamati Lisa offers solution focused coaching sessions to help you find the right answers to your challenges. Topics Lisa can help with:  Lisa is a Genetics Practitioner, Health Optimisation Coach, High Performance and Mindset Coach. She is a qualified Ph360 Epigenetics coach and a clinician with The DNA Company and has done years of research into brain rehabilitation, neurodegenerative diseases and biohacking. She has extensive knowledge on such therapies as hyperbaric oxygen,  intravenous vitamin C, sports performance, functional genomics, Thyroid, Hormones, Cancer and much more. She can assist with all functional medicine testing. Testing Options Comprehensive Thyroid testing DUTCH Hormone testing Adrenal Testing Organic Acid Testing Microbiome Testing Cell Blueprint Testing Epigenetics Testing DNA testing Basic Blood Test analysis Heavy Metals  Nutristat Omega 3 to 6 status and more  Lisa and her functional medicine colleagues in the practice can help you navigate the confusing world of health and medicine . She can also advise on the latest research and where to get help if mainstream medicine hasn't got the answers you are searching for whatever the  challenge you are facing from cancer to gut issues, from depression and anxiety, weight loss issues, from head injuries to burn out to hormone optimisation to the latest in longevity science. Book your consultation with Lisa    Join our Patron program and support the show Pushing the Limits' has been free to air for over 8 years. Providing leading edge information to anyone who needs it. But we need help on our mission.  Please join our patron community and get exclusive member benefits (more to roll out later this year) and support this educational platform for the price of a coffee or two You can join by going to  Lisa's Patron Community Or if you just want to support Lisa with a "coffee" go to  https://www.buymeacoffee.com/LisaT to donate $3   Lisa's Anti-Aging and Longevity Supplements  Lisa has spent years curating a very specialized range of exclusive longevity, health optimizing supplements from leading scientists, researchers and companies all around the world.  This is an unprecedented collection. The stuff Lisa wanted for her family but couldn't get in NZ that's what it's in her range. Lisa is constantly researching and interviewing the top scientists and researchers in the world to get you the best cutting edge supplements to optimize your life.   Subscribe to our popular Youtube channel  with over 600 videos, millions of views, a number of full length documentaries, and much more. You don't want to miss out on all the great content on our Lisa's youtube channel. Youtube   Order Lisa's Books Lisa has published 5 books: Running Hot, Running to Extremes, Relentless, What your oncologist isn't telling you and her latest "Thriving on the Edge"  Check them all out at  https://shop.lisatamati.com/collections/books   Perfect Amino Supplement by Dr David Minkoff Introducing PerfectAmino PerfectAmino is an amino acid supplement that is 99% utilized by the body to make protein. PerfectAmino is 3-6x the protein of other sources with almost no calories. 100% vegan and non-GMO. The coated PerfectAmino tablets are a slightly different shape and have a natural, non-GMO, certified organic vegan coating on them so they will glide down your throat easily. Fully absorbed within 20-30 minutes! No other form of protein comes close to PerfectAminos Listen to the episode with Dr Minkoff here:    Use code "tamati" at checkout to get a 10% discount on any of their devices.   Red Light Therapy: Lisa is a huge fan of Red Light Therapy and runs a Hyperbaric and Red Light Therapy clinic. If you are wanting to get the best products try Flexbeam: A wearable Red Light Device https://recharge.health/product/flexbeam-aff/?ref=A9svb6YLz79r38   Or Try Vielights' advanced Photobiomodulation Devices Vielight brain photobiomodulation devices combine electrical engineering and neuroscience. To find out more about photobiomodulation, current studies underway and already completed and for the devices mentioned in this video go to www.vielight.com and use code “tamati” to get 10% off     Enjoyed This Podcast? If you did, subscribe and share it with your friends! If you enjoyed tuning in, then leave us a review and share this with your family and friends. Have any questions? You can contact my team through email (support@lisatamati.com) or find me on Facebook, Twitter, Instagram and YouTube. For more episode updates, visit my website. You may also tune in on Apple Podcasts.  To pushing the limits, Lisa and team

In this JCO Article Insights episode, Davide Soldato interviews Dr. Naqash  from University of Oklahoma. Dr. Naqash provides insight into the original article published in the July JCO issue: “Safety and Activity of Immune Checkpoint Inhibitors in People Living With HIV and Cancer: A Real-World Report From the Cancer Therapy Using Checkpoint Inhibitors in People Living With HIV-International (CATCH-IT) Consortium”. The interview offers a deep dive into the manuscript results on efficacy and safety of Immune Checkpoint Inhibitors in this specific population and offers insights on future research direction in this space. TRANSCRIPT The guest on this podcast episode has no disclosures to declare.  Davide Soldato: Welcome to this JCO Article Insights episode for the July issues of JCO. This is Davide Soldato and today I will have the pleasure of interviewing Dr. Abdul Rafeh Naqash, the author of the manuscript titled "Safety and Activity of Immune Checkpoint Inhibitors in People Living with HIV and Cancer: A Real World Report from the Cancer Therapy Using Checkpoint Inhibitors in People Living with HIV-International Consortium."  Dr. Naqash is an Assistant Professor of Hematology-Oncology at the University of Oklahoma and a Medical Oncologist working at the Stephenson Cancer Center. His research interests revolve around early-phase clinical trials in solid tumors, lung cancer, and the study of immunotherapy, biomarkers, and resistance.  Welcome, Dr. Naqash, and thank you for accepting our invitation today. Dr. Abdul Rafeh Naqash: Dr. Soldato, thanks so much for having me. I'm really excited to discuss this article with you today. Davide Soldato: So I just wanted to go a little bit over the manuscript with you. So basically, this is a retrospective multicenter study that was conducted across the US, Europe, and Australia by the CATCH-IT Consortium. And so the aim of the study was really to investigate the safety and the activity of immune checkpoint inhibitors among patients diagnosed with cancer and also living with HIV. The article examined two different cohorts, and I just wanted to start with a brief explanation of how the two cohorts were built so that our readers can get a little bit of understanding of what you did then. Dr. Abdul Rafeh Naqash: Sure. Before I take a deep dive into the cohorts, Dr. Soldato, I would definitely like to mention the premise and the background for this paper as to why we did what we did. And one of the primary reasons was that people living with HIV, historically, there have been very limited number of trials that have included these individuals. So it becomes a very important question from a disparity standpoint. And most often we end up, in the real world setting, we end up extrapolating data from clinical trials, but not necessarily know what is the outcome of these individuals in the real world setting.  So there have been some very important studies in the last three years or so in people with HIV as far as clinical trials with checkpoint inhibitors go, but most of those trials have been limited by the number of patients, number of people that have been part of those trials. So we wanted to understand it from a broad perspective, whether it is from a broad geographic perspective or from a heterogeneous patient population perspective, which is why we built this consortium called the CATCH-IT Consortium, which basically stands for Cancer Therapy Using Checkpoint Inhibitors in People Living With HIV-International Consortium. And this required a lot of effort from a lot of different centers, including those in the US, Europe, and Australia, as you mentioned. And then we ended up having data worth around 400 plus patients, close to 400 patients or so. And then we wanted to look at obviously outcomes, whether it's related to a certain tumor such as lung cancer, which we did in this case, or a pan tumor assessment of toxicities and safeties.  So, to your question, the cohorts that we basically had, we had close to approximately 390 patients that we included in the safety analysis. So first we looked at the safety analysis, which was the entire cohort, and then out of those we excluded around 12 patients or so. Those were patients that were treated in the adjuvant setting. So in the metastatic advanced setting, we had close to 378 individuals that we assessed clinical outcomes for. So, response rates, progression-free survival, and overall survival. And then as far as a separate cohort, we looked at non-small cell lung cancer, which was the most commonly represented tumor type, with approximately 111 patients that had non-small cell lung cancer. We did exclude a certain proportion of those that were earlier stage, stage III.  So in the stage IV, basically we ended up matching in this separate cohort, around 60 odd patients or so of non-small cell lung cancer to 110 stage four, non-small cell lung cancers. So basically it was a one-to-two matching and we chose the same site. So if a site had, let's say, two people with HIV and lung cancer treatment checkpoint, we tried to match it to approximately four to five patients from the same site and we used some variables for matching so that we had some level of homogeneity between the HIV patient population and the non-HIV positive lung cancer individuals. So that's basically cohort A was around 370-something patients, tumor agnostic advanced metastatic setting. Cohort B was lung cancer individuals matched to non-HIV positive lung cancer treatment checkpoint inhibitors. Davide Soldato: Thank you very much. That was very clear. Just to go back to what you were saying before because I think that this is very interesting. You mentioned that patients living with HIV were mostly excluded from clinical trials and in the few that included them, there were some restrictive criteria in terms for example of CD4-positive cells in the blood. And so I was wondering if when you included the patients inside of this cohort, you also had this type of exclusion criteria or you chose a broader population to make the results more generalizable and applicable in clinical practice.  Dr. Abdul Rafeh Naqash: Right, a very important question. Thank you, Dr. Soldato. So yes, previous clinical trials have had some level of restrictions as far as the inclusion of these individuals, but in our study, this was a real-world study, basically, patients whoever presents to the clinic with a history of HIV, they were all included. So we did not restrict it to certain CD4 counts or viral loads because the important thing was we wanted to understand the ground situation of how these individuals do, irrespective of some of these limitations. As far as what we identified as baseline CD counts or HIV viral load positivity, we took three months before immune checkpoint initiation as a cut off so obviously there's a limitation there. We didn't have results of these CD4, CD at a viral load assessments done like the day of or the week before in some patients. So we took three months and we included individuals that had received at least one or more dose of immune checkpoint therapy between January of 2015 to October of 2021, which was our database lock.  And then obviously the regimens included immune checkpoint anti-PD1, PD-L1 monotherapy, or in combination with other anticancer agents including anti-CTLA-4 or chemotherapies targets, which is important to point out here. So the trials that have been mostly done in this space are single-agent checkpoint inhibitors or anti-PD1 with anti-CTLA-4. There's not much data for immune checkpoint inhibition combined with other agents such as targeted therapies, chemotherapies. So we had some of that data in this cohort, which kind of made it interesting. Davide Soldato: Yeah, I think that it's very interesting and it's very wise to choose very broad eligibility criteria for these type of studies because it really answered to the question that we identified and that we spoke about in the beginning.  So going back to the results, you said that the cohort A, so the one that included all the patients, irrespectively of the type of tumor that was diagnosed, it was mainly for evaluating what was the safety of immune checkpoint inhibitors in patients living with HIV and with a concurrent cancer diagnosis. So I was wondering if in this cohort you identified some differences compared to historic data in terms of, for example, incidence of grade three or higher toxicities or incidence of immune-related adverse events in general, and if maybe there was some adverse events that was very characteristic or particular in this cohort. Dr. Abdul Rafeh Naqash: So immune-adverse events is a very interesting question not only from this cohort but in general because it overlaps with this question of autoimmunity and cross T cell cross reactivity. And this is a unique patient population where we have the ability, although not fully but to some extent, to look at the role for CD counts and also look for patterns of adverse events.  To answer your first part of the question, we didn't see any significant differences for the types of adverse events. We did see the incident was a little lower than what you would expect in the real-world setting for non-HIV individuals. Whether that has something to do with how the immune system is constructed in these individuals, nobody knows. We did look at CD4 and CD8 counts. As far as absolute CD4 counts, about 200 or below 200, we didn't see a difference as far as the cumulative incidence for immune checkpoint inhibitor-related adverse events. When we did a ratio of CD4 to CD8 of greater than 0.4 and compared it to less than 0.4, we did see that at around 24 weeks, there was a difference in terms of the cumulative incidence for adverse events. It was around 10% versus 26% when we use that cut-off of 0.4, suggesting that there might be some role of how the peripheral immune system results in the related adverse events in these individuals, but it's a very important question.  I think there are ongoing evaluations that are being done from other prospective studies that had collected blood samples in these individuals. But generally, we saw the same range of adverse events, diarrhea, colitis, pneumonitis, hepatitis. We did have a few patients who had  a history of opportunistic infections, but we didn't see any significant reactivation there which was part of the safety assessment in our analysis.    Davide Soldato: So basically, because I think that in HIV patients, even if those included in the study were almost all were on antiretroviral therapy, but you didn't observe any opportunistic infection that developed during the course of immunotherapy. Dr. Abdul Rafeh Naqash: You're absolutely right, we did not. In fact, we are trying to look at that in a different setting, in a different cohort because there have been some data on mycobacterial reactivation in individuals in general, not just HIV, but in our cohort of 400 odd patients, we did not see any new opportunistic infections. Davide Soldato: I think that one aspect that pops into my mind right now is also that we have kind of some data regarding also possible HPV reactivation in these types of patients treated with immune checkpoint inhibitors. So maybe that could be also something that you would be interested to look at in the future, I imagine.  Dr. Abdul Rafeh Naqash: Yes, we are planning to look at HPV-driven cancers actually for starters, anal and head and neck. We are also looking at hepatitis B-related HCC in a separate ongoing cohort. So there are definitely subsequent steps that we are currently involved in as far as viral-driven cancers and concurrent HIV is concerned. Davide Soldato: Thank you. I think that's very interesting. And I was wondering, you mentioned in the beginning that this patient clearly they have some degree of immune dysregulation or at least some type of dysfunction in terms of immune presentation and immune activation. So I think that one of the concerns or one of the worries of using immune checkpoint inhibitors in this population could also be that the efficacy that we see in patients that do not have HIV could be lower. Could you comment on this if you found any differences both in the cohort including all cancer, but also in the cohort B, that I think you had the strategic idea of pairing these patients living with HIV with patients that were not living with HIV. So I think that this brings very important data to the space. Dr. Abdul Rafeh Naqash: Yes, we tried to look at this one from a tumor-agnostic perspective and a tumor-specific perspective. So the tumor agnostic perspective was looking at a different set of cancers which included skin cancer, melanoma, lung cancer, non-Hodgkin's lymphoma, small cell head and neck, and a couple of other cancers. And one of the things we noticed was that there was a trend, so there was differential efficacy as far as the cancer type is concerned. So for example, skin, Hodgkin's lymphoma, Kaposi sarcoma, melanoma had the highest response rates, somewhere in the range of 60s to 40s. On the other hand, viral-driven cancers such as anal cancer, HCC, head and neck actually had very low response rates, less than 15% or so. So that begs the question of what is going on and we don't necessarily know, which is why we are trying to concentrate on the viral-driven cancers first. Because as you know, melanoma, Kaposi's do have historically shown better responses to checkpoint inhibitors.   Now do we know if when we compare these responses or survival to non-HIV individuals in clinical trials, are the outcomes similar? I would say in some of the tumor types the outcomes were somewhat inferior and in some of the tumor types the outcomes were somewhat similar. So for example, lung, we did compare non-small cell lung cancer. As I mentioned, we had two cohorts, we matched it to a non-HIV cohort and there we looked at progression-free survival and overall survival. And again the caveat is that this is a retrospectively matched cohort, this is not a prospectively matched cohort. So these are individuals that are not matched for each and every variable. They're matched for certain top three or four variables as much as we could accommodate. And based on that we didn't see a difference in the progression-free survival and the overall survival when we did an assessment.  In fact, we looked at it at a 42 month period where we looked at the restricted median survival time and it was not different, was around 17.8% for people with HIV and 18.4% for people without HIV as far as progression-free survival, and around 42% and 41% overall survival at the two-year mark. So basically there is not much significant difference which reiterates the fact that in the right setting, these individuals could be safely treated with immune checkpoint inhibition and could perhaps have similar outcomes. Maybe not in all tumor types, but in some tumor types. But at the end of the day, and we mentioned this in our manuscript also in subsequent work that we are trying to do, we have emphasized on the fact that it has to be a multidisciplinary discussion between the patient, the physician, the medical oncologist, the treating oncologist, and the infectious disease person. Because these individuals have a lot of complicated aspects because of the underlying HIV and taking that into perspective and then assessing risk-benefit is an important discussion.  So the goal of this work was not to establish that immune checkpoint inhibitors are absolutely beneficial or absolutely safe. The goal was more to create awareness that people in the real-world setting actually can benefit, which the next step would be to have more trials and perhaps modify inclusion criteria in clinical trials so that you can have a more inclusive approach, including these individuals.  Davide Soldato: Coming back to the multidisciplinary approach because I think that this is very interesting and should be really implemented when we have this type of patient. From the data that you collected, did you add any indication that maybe this patient treated in the real-world setting were not managed in such a multidisciplinary way? Dr. Abdul Rafeh Naqash: The easiest way to point that out is that most of these people or many of these individuals did not have HIV viral loads or CD4 counts done before treatment initiation. And that's an indirect surrogate for telling you that these are things that should have been thought of, but were not thought of if the individual taking care of these people either did not have expertise as far as HIV is concerned or did not have a colleague on the infectious disease side who was actively managing these people.  So that's an important indirect way where we kind of got a sense that there has to be more awareness about multidisciplinary care. And especially the immune adverse event situation in these individuals can get complicated because of the way their immune system is constructed and having that multidisciplinary care is very important. We didn't specifically collect data on what teams or what subspecialists were involved in each individual's care, but I think that would be an important assessment for maybe a future quality improvement project to look at why or how some of those things were not done so that it can lead to future improvements. Davide Soldato: So, just expanding on that, you said that you didn't have much data in terms of CD4 cells or in terms of viral load. But for what you had inside of your cohort, did you see any modification of these parameters that we know that are very important in patients living with HIV under immune checkpoint inhibitors therapy? Dr. Abdul Rafeh Naqash: Again, a very important immunological question, I think as far as what we saw- so we had close to around 74, 75 individuals that had CD4 T cell counts available. And we didn't see differences between baseline and post-immune checkpoint therapy changes in CD4 counts. Similarly, we didn't see a difference as far as HIV viral load and we had HIV viral loads present in around 107 individuals and we didn't see a difference. Now, again, 30% of our cohort was CD4 count less than 200, and 70% was CD4 count more than 200, , which is again, important to highlight because many trials don't take individuals with the CD4 count less than 200. But in general, we did not see a difference in this pre and post-assessment both for viral load and both for CD4 count. Now trials in this space have ongoing assessments that they are doing. The AIDS Malignancy Consortium does have a trial looking at changes in CD4/CD8 counts or viral loads. In fact, the CITN trial which is a pembrolizumab trial published a couple of years back did have an assessment done as far as CD4 counts and viral loads are concerned. And I think they did see a slight increase in the CD4 counts and there are some aspects about how the immune system may change with an immune checkpoint inhibitor. But I think the strength of the data is not that much, and I think we probably need more patient samples to assess why or how some of that could change or what implications it would have for patients.  Now, there is another concept of HIV viral latency removal that some of the listeners might have heard of, especially in the HIV setting, where you were given an immune checkpoint inhibitor and it can lead to reversal or reduction of the HIV reservoir, which can somehow impact the CD4 counts, and also lead to elimination of the viruses through CD8. But again, that's a more complicated assessment and we didn't have data for it.   Davide Soldato: Thank you very much. That was very interesting also for future perspectives in this topic.  I just wanted to ask you if the idea for the research came more from ensuring equity in terms of care delivery for patients living with HIV or if it was more also to investigate the immunological components that we discussed just as far or a good mix of the two. Dr. Abdul Rafeh Naqash: I think the idea actually stemmed from this individual who's the first author, Dr. Talal El Zarif and co-first author Dr. Amin Nasser from Dana-Farber, reached out a year and a half back and they wanted to look at outcomes from an HIV standpoint and see what the real world setting is. And the goal was they would have their data and we would have our data and we would eventually collect the data together or combine the data together. But then after some conversations, we started looking at the available data, the available literature, saw that there was a decent gap in what we know. And I know there are some brilliant groups in the HIV space, especially at the NCI. In fact, Dr. Kate Lurain and Dr. Ramaswami are good collaborators of ours and they worked in this space and are currently developing trials in this space. But it just did seem like this would be a more interesting approach of answering a real-world question and then also looking at the disparities of it because as an early-phase drug development trialist, I still see a lot of trials, in fact, majority of the trials, say people with HIV or history of HIV are excluded.  Now, the NCI has made important efforts in that space of including those individuals, but I think we still have some ways to go. So basically the idea came from two trainees who were extremely enthusiastic and wanted to pursue this. And I, obviously, seeing their level of enthusiasm and excitement, I was excited too. And then importantly, if you look at the paper, we have a bunch of authors, we have close to 79, 80 authors on that paper. And the primary reason was that each center contributed in certain ways, including patients' data and then expertise. And this ended up being a huge community effort from the oncology community, where everybody's individual effort led to something like this coming to fruition.  So it was a multitude of different aspects, but yes, it all started with a question of how these individuals do and the current data where they're missing gaps, and we wanted to sort of supplement those gaps and provide insights using this important real-world data set. Davide Soldato: Thank you very much for the insight on how the idea came to be.  Is there anything else you would like to add or to summarize for our listeners? Dr. Abdul Rafeh Naqash: Well, first of all, I appreciate the opportunity to discuss our paper here. I would like to thank you and of course the JCO staff for organizing this, and also the JCO Journal for giving us the opportunity to publish this important work. Some of the things that we would like to highlight as outcomes from this paper, as we sort of discussed, but to summarize those: we saw that we didn't have any significant safety concerns, obviously. We saw that some patients in certain tumor types do benefit, similar to what you might expect in a non-HIV setting in the real world as well.  And of course, this was the largest real-world data set of people with HIV and cancer. And we have ongoing efforts in different directions, as I mentioned to you. And we are more than happy to collaborate with anybody who has good ideas because this is a community-level data set. It was created for the community, by the community, and the goal is to utilize this data set. So if there is a listener out there who's interested in collaborating, who has an idea, we're more than happy to share the data set in the right setting. And then hopefully, everybody has the opportunity to lead different efforts in the space. Davide Soldato: Thank you again for being with us today, Dr. Naqash. To hear more from Dr. Naqash, please check out ASCO's JCO Precision Oncology Conversation Podcast.  So this is Davide Soldato. In this episode of JCO Article Insights, we discussed the results of the manuscript titled, “Safety and Activity of Immune Checkpoint Inhibitors in People Living with HIV and Cancer: A Real World Report from the Cancer Therapy Using Checkpoint Inhibitors in People Living with HIV-International Consortium.” Thank you for your attention and stay tuned for the next episode.  The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.  Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.      

"单极抑郁症中的免疫细胞组成：全面的系统评价和荟萃分析 NinaVindegaardSørensen，Beate Holmelund Frandsen，Sonja Orlovska-Waast，Terkild Brink Buus，NielsØdum，Rune Haubo Christensen和Michael Eriksen Benros 抽象的 抑郁症与" "启动AD- #TheMummichogBlogoFmalta Amazon Top和Flash Deals（会员链接 - 如果您通过以下链接购买，您将支持我们的翻译）-https：//amzn.to/3feogyg 仅在一次搜索中比较所有顶级旅行网站，以在酒店库存的最佳酒店交易中找到世界上最佳酒店价格比较网站。 （会员链接 - 如果您通过以下链接购买，您将支持我们的翻译）-https：//www.hotelscombined.com/?a_aid=20558 “因此，无论您希望别人对您做什么，也对他们做，因为这是法律和先知。”“ #Jesus #Catholic。 “从受孕的时刻，必须绝对尊重和保护人类的生活。从他生存的第一刻起，必须将一个人承认为拥有一个人的权利 - 其中每种无辜者都是无辜的权利。”天主教教堂的教理2270。 堕胎杀死了两次。它杀死了婴儿的身体，并杀死了母亲的科学。堕胎是深刻的反妇女。它的受害者中有三个季节是女性：一半的婴儿和所有母亲。 流畅的马耳他无线电是马耳他的第一号数字广播电台，演奏您的轻松最爱 - Smooth提供了“无混乱”的混音，吸引了35-59个核心观众，提供柔和的成人现代经典。我们操作一个流行曲目的播放列表，并定期更新。 https://smooth.com.mt/listen/ 马耳他是一颗地中海宝石，等待被发现。马耳他拥有文化和历史，娱乐和放松，冒险和兴奋的独特结合，也是出国留学的理想之地。实际上，它拥有世界上最优秀的学习机构。 -https：//www.visitmalta.com/ 关注电报：https：//t.me/themummichogblogdotcom Tumblr：https：//www.tumblr.com/themummichogblogofmalta blogspot：https：//themummichogblogofmalta.blogspot.com/ 论坛：https：//groups.google.com/g/themummichogblog Facebook：https：//www.facebook.com/groups/chinesecommunitymalta 结束广告" "炎症性病理生理机制，包括循环免疫细胞量的改变。然而，与健康对照组相比，在过去20年中，没有在过去20年内重新评估抑郁症患者的血液和脑脊液（CSF）的循环免疫细胞。这项研究的目的是与健康对照组相比，系统地评估单极抑郁症患者的血液和CSF中的循环免疫细胞。搜索数据库直到2021年2月12日。使用固定和随机效应模型，将104项研究包括在荟萃分析中。抑郁症患者的总体白细胞计数明显更高（35个研究； SMD，0.46; 95％CI：0.31-0.60，I2 = 68％），中性粒细胞计数较高（24个研究； SMD，0.52; 95％CI：0.33-0.71：0.33-0.71 ，与健康对照组相比，I2 = 77％）和更高的单核细胞计数（27个研究； SMD，0.32; 95％CI：0.11-0.53，I2 = 77％）。白细胞计数在住院患者中较高，表明与抑郁症的严重程度有关。此外，几个淋巴细胞亚群（包括较高的天然杀伤细胞和T细胞亚群）发生了重大改变。较高的中性粒细胞/淋巴细胞比（11个研究； SMD = 0.24; 95％CI：0.06-0.42，I2 = 73％），CD4/CD8细胞比率（26个研究； SMD = 0.14; 95％CI：0.01-28，I2，I2，I2，I2，I2 = 42％）和T辅助器17/T调节率（2个研究； SMD = 1.05; 95％CI：0.15–1.95，I2 = 86％）在患者中与健康对照组相比在患者中发现。与对照组相比，患者的CSF白细胞计数更高（3个研究； SMD = 0.20； 95％CI：0.01-0.38，I2 = 0％）。没有CSF细胞子集的数据。这项研究表明，与健康对照组相比，单极抑郁症患者有几种血液免疫细胞的改变，包括主要白细胞亚群和更专业的免疫细胞亚群。 https://www.nature.com/articles/s41380-022-01905-z "

SARS-CoV-2 affects the brain.Measure your blood oxygen level, ECG from anywhere and see how fit you are -SURELY, BUT CAN YOU SEE ON YOUR CELL PHONE ANY OF YOUR NEUROTRANSMITTERS SUCH AS DOPAMINE AND SEROTONIN? CAN YOU SEE HOW YOU FEEL? CAN YOU SEE HOW YOUR MEDICATIONS HAVE AFFECTED YOUR NEUROTRANSMITTER? ARE YOUR NEUROTRANSMITTERS IN GOOD ORDER? OUR SHOW TONIGHT IS ABOUT THE BRODERICK PROBE, a tiny sensing device.They are so sturdy. They do not break if you were to drop them. They make sense. Sensors make sense.After all, Bold Brave Media is investing hundreds of thousands of dollars in the BRODERICK PROBE! you will hear them, these ads you know, every day all day to tell the world, 20 million listeners on 16 platforms that we have at CUNY, the best technology in the world. It is nanobiotechnology. Nanobiotechnology is about to rule the world in medicine, in academia, in industry, in pharmaceuticals and the list goes on!The nanobiosensors from the Broderick Laboratory are designed in many formulas, shapes and sizes to fit a specific function to help the animal and the patient.Tonight, we are going to tell you why this nanoprobe is the best!The publication concerns "Depression and SARS-CoV-2". Running Title: Neuroimaging a Cytokine Storm "Live" in Freely Moving Subjects by Broderick and Cofresi in the Compendium on the Neuroscience of Depression (Eds. Drs. Preedy and Patel), Elsevier. UK and USAChapter 11, 2020Kethia Calixte is with us-from Neurobiology-the famous and best Medical 10000. Kethia is telling us about it!Neuroimaging a Cytokine Storm by Transducing IL-1α to Hippocampal Cornu Ammonis: COVID-19 SARS-CoV-2 . TRunning Title: Neuroimaging a Cytokine Storm "Live" in Freely Moving Subjects[1] Corresponding AuthorPatricia A. Broderick, PhD and co-author-Steven Cofresi, BS (Steven is from MED 10000)We watched online as the feared "hippocampal cytokine storm" was imaged in the depressed subject while immune T cell ratio CD4/CD8 was reversed. Tracking cytokine neuroinflammation transduced to HPC CA-1 neurons directly on line while the subject is walking enables direct extrapolation to immune brain dysfunction in SARS-Cov-2 virus (Covid 19) patient data. It is imaged by the neurotransmitters that defines a medical condition or the healthy condition or the condition that is medicated. it is called, signalling! The profile for Xanax matches the profile, the signalling for the healthy adapted condition after the cytokine storm! Xanax was approved for depression through the work of Dr. Broderick to the FDA through the Pharmacia/Upjohn Company in Kalamazoo, MI, USA. Publication recognized by the Dean for Research in CUNY School of Medicine and the Collective Dean for Research at CUNY.We will also tell you about COVAXXhttps://www.unmc.edu/news.cfm?match=26198 UNMC, COVAXX sign agreement paving way for clinical trials of COVAXX therapeuticSeptember 10, 2020 Nebraska Medicine and Univ of Nebraska Medical Center partnering with United Biomedical Inc.and more about vaccines from CUNY Med at CCNY!Dr. Paul GottliebTechnoVax regarding COVID-19 vaccines has been highlighted by the Associated Medical School of New York. Perhaps he can tell us more about it tomorrow. Here are the links:https://twitter.com/AMSNewYork/status/1308119303489814530https://www.ccny.cuny.edu/news/cuny-med-school-technovax-report-covid-19-vaccine-breakthroughDr. Patricia A. Broderick is honored as Top Innovator by Top Registry 100 featuring Education and Medicine, front page and featured story! Printed now, 20201A special protein with the fatty coat antibody platform is published in the Broderick Patent Portfolio held by Eazysense Nanotechnologies Inc. further held by the CUNY Technology Commercialization Office. Immunologists and Virologists etc. are invited for discussion and futur

Dr Guerra swings hard at Treg and naive CD4+/CD8+ lymphocytes in immunosenescence and the potential for infection with aging while accumulating T memory cell lineages confined to antigen./pathogen exposure including vaccine-associated immunizations. Newe paper disussed today: .Brain Behav Immun 2018 Oct; 73: 546–549.doi: 10.1016/j.bbi.2018.06.019. Epub 2018 Jun 22. PLeasse donate to Authentic Biochemistry! I need your financial support in these trying times. --- Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support

Hypersensitivity pneumonitis (HP) also called exogenous allergic alveolitis = extrinsic allergic alveolitis in children is an uncommon condition and may not be recognized and treated appropriately. To assess current means of diagnosis and therapy and compare this to recommendations, we used the Surveillance Unit for Rare Paediatric Disorders (ESPED) to identify incident cases of HP in Germany during 2005/6. In addition, cases of HP reported for reference from all over Germany to our center in the consecutive year were included. Twenty-three children with confirmed pediatric HP were identified. All (age 9.4 y (4.4-15.1) presented with dyspnoea at rest or with exercise, mean FVC was 39% of predicted, seven of the 23 children already had a chronic disease state at presentation. IgG against bird was elevated in 20, and against fungi in 15. Bronchoalveolar lavage was done in 18 subjects (41% lymphocytes, CD4/CD8 1.99), and lung biopsy in 6. Except 2, all children were treated with prolonged courses of systemic steroids. Outcome was not favourable in all cases. Late diagnosis in up to a quarter of the children with HP and inappropriate steroid treatment must be overcome to improve management of HP. Inclusion of children with HP into international, web-based registry studies will help to study and follow up such rare lung diseases.

Background: Animal models of human inflammatory diseases have limited predictive quality for human clinical trials for various reasons including species specific activation mechanisms and the immunological background of the animals which markedly differs from the genetically heterogeneous and often aged patient population. Objective: Development of an animal model allowing for testing therapeutics targeting pathways involved in the development of Atopic Dermatitis (AD) with better translatability to the patient. Methods: NOD-scid IL2R gamma(null) mice engrafted with human peripheral blood mononuclear cells (hPBMC) derived from patients suffering from AD and healthy volunteers were treated with IL-4 and the antagonistic IL-4 variant R121/Y124D (Pitrakinra). Levels of human (h) IgE, amount of B-, T- and plasma-cells and ratio of CD4 : CD8 positive cells served as read out for induction and inhibition of cell proliferation and hIgE secretion. Results were compared to in vitro analysis. Results: hIgE secretion was induced by IL-4 and inhibited by the IL-4 antagonist Pitrakinra in vivo when formulated with methylcellulose. B-cells proliferated in response to IL-4 in vivo; the effect was abrogated by Pitrakinra. IL-4 shifted CD4 : CD8 ratios in vitro and in vivo when hPBMC derived from healthy volunteers were used. Pitrakinra reversed the effect. Human PBMC derived from patients with AD remained inert and engrafted mice reflected the individual responses observed in vitro. Conclusion: NOD-scid IL2R gamma(null) mice engrafted with human PBMC reflect the immunological history of the donors and provide a complementary tool to in vitro studies. Thus, studies in this model might provide data with better translatability from bench to bedside.

The long pentraxin PTX3 has multiple roles in innate immunity. For example, PTX3 regulates C1q binding to pathogens and dead cells and regulates their uptake by phagocytes. It also inhibits P-selectin-mediated recruitment of leukocytes. Both of these mechanisms are known to be involved in autoimmunity and autoimmune tissue injury, e.g. in systemic lupus erythematosus, but a contribution of PTX3 is hypothetical. To evaluate a potential immunoregulatory role of PTX3 in autoimmunity we crossed Ptx3-deficient mice with Fas-deficient (lpr) C57BL/6 (B6) mice with mild lupus-like autoimmunity. PTX3 was found to be increasingly expressed in kidneys and lungs of B6lpr along disease progression. Lack of PTX3 impaired the phagocytic uptake of apoptotic T cells into peritoneal macrophages and selectively expanded CD4/CD8 double negative T cells while other immune cell subsets and lupus autoantibody production remained unaffected. Lack of PTX3 also aggravated autoimmune lung disease, i.e. peribronchial and perivascular CD3+ T cell and macrophage infiltrates of B6lpr mice. In contrast, histomorphological and functional parameters of lupus nephritis remained unaffected by the Ptx3 genotype. Together, PTX3 specifically suppresses autoimmune lung disease that is associated with systemic lupus erythematosus. Vice versa, loss-of-function mutations in the Ptx3 gene might represent a genetic risk factor for pulmonary (but not renal) manifestations of systemic lupus or other autoimmune diseases.

The existence of four subpopulations in resting porcine T lymphocytes is documented. In addition to the two known subpopulations which are typified by a mutually exclusive expression of either the CD8 or the CD4 differentiation antigen, CD4-CD8+ and CD4+CD8- T lymphocytes, respectively, two unusual subpopulations were prominent not only in peripheral blood, but also in lymphoid tissues: CD4-CD8- T lymphocytes expressing neither of these antigens and CD4+CD8+ T lymphocytes coexpressing both antigens. While CD4+CD8+ lymphoblasts have been found also in other species, resting T lymphocytes with that phenotype are without precedent among all species analyzed to date. This unique composition of the porcine T lymphocyte population has to be taken into consideration when the swine is used as a large animal model in experimental medicine.