Reset OS for cancer treatment
Your recent AMA podcast about immunotherapy was fascinating. I was in the middle of a clinical trial using a combination of Prembro and IO102-103 as the initial pre-adjuvant treatment before unilateral Nodal Dissection and TORS (performed at Hopkins!). My condition is Regional Metastatic SCCHN with PD-1 expression. The trial did not offer me significant progress so I am now moving into a 4 week cycle of chemotherapy prior to surgery. If the chemotherapy is not successful I will pivot to radiation post surgery. Through this exercise I’ve learned that although I have a “treatable” disease, nobody gets out of treatment for free. Through all the treatments and surgeries I must be lowering my OS rate to some degree. How do I get those months/years back?
Creatine supplementation for kidney donor
I've donated a kidney, and as such I have been advised to not supplement with Creatine. The more I learn about Creatine, however, the more it seems like the reason for that suggestion is that Creatine supplementation raises creatinine, which is a marker for kidney function- but as you've mentioned previously, it is a bad marker of kidney function. Would Creatine actually damage my kidney, or would it just hurt my test results with no kidney damage?
Leucine linked to higher rates of arteriosclerosis
Would love to have you review this this study appearing in Nature Metabolism, "Identification of a leucine-mediated threshold effect governing macrophage mTOR signalling and cardiovascular risk," from Xiangyu Zhang and colleagues at the University of Pittsburgh with analsis by F. Perry Wilson, MD on Medscape. https://www.medscape.com/viewarticle/1000179?ecd=WNL_trdalrt_pos1_240221_etid6327063&uac=430553BY&impID=6327063 Many thanks.
Leucine, MTOR, and Increased CVD Risk
Hi…I sent an earlier request regarding reviewing this study. I don’t have access to the entire paper in Nature, however, it does mention Leucine, MTOR and rapamycin and I thought this would be of interest to Peter and all of you. Thanks for taking a look. Very curious to know what your team thinks about this: Identification of a leucine-mediated threshold effect governing macrophage mTOR signalling and cardiovascular risk Abstract High protein intake is common in western societies and is often promoted as part of a healthy lifestyle; however, amino-acid-mediated mammalian target of rapamycin (mTOR) signalling in macrophages has been implicated in the pathogenesis of ischaemic cardiovascular disease. In a series of clinical studies on male and female participants (NCT03946774 and NCT03994367) that involved graded amounts of protein ingestion together with detailed plasma amino acid analysis and human monocyte/macrophage experiments, we identify leucine as the key activator of mTOR signalling in macrophages. We describe a threshold effect of high protein intake and circulating leucine on monocytes/macrophages wherein only protein in excess of ∼25 g per meal induces mTOR activation and functional effects. By designing specific diets modified in protein and leucine content representative of the intake in the general population, we confirm this threshold effect in mouse models and find ingestion of protein in excess of ∼22% of dietary energy requirements drives atherosclerosis in male mice. These data demonstrate a mechanistic basis for the adverse impact of excessive dietary protein on cardiovascular risk. https://www.nature.com/articles/s42255-024-00984-2