erictopol.substack.com/p/your-thymus-and-your-healthspan
4 corrections found
The thymus health score outperformed programmed death ligand-1 (PD-L1)and tumor mutation burden (TMB) assay of the tumor
The Nature paper did not report that thymic health outperformed PD-L1 or TMB; it said thymic health had similar average effect sizes and added independent, complementary prognostic information.
Full reasoning
This overstates the result of the cited Nature study. The paper says "the average effect sizes of thymic health were similar to those of PD-L1 and TMB", not better than them. It also concludes that thymic health provides independent and potentially complementary prognostic information beyond tumour-centric biomarkers. In other words, the authors argue thymic health is a useful additional biomarker, but they do not claim it outperformed PD-L1 or TMB overall.
1 source
- Thymic health and immunotherapy outcomes in patients with cancer | Nature
We found that the average effect sizes of thymic health were similar to those of PD-L1 and TMB... Together, these data indicate that thymic health provides independent and potentially complementary prognostic information beyond clinical variables and tumour-centric biomarkers.
and 1.5-fold increase in autoimmune diseases.
The NEJM thymectomy study did not find a 1.5-fold increase in autoimmune disease in the overall matched primary cohort; that increase appeared only in a restricted subgroup after exclusions.
Full reasoning
This sentence presents the autoimmune finding as a general result of the study, but the study's primary matched cohort did not show a substantial difference in autoimmune disease risk overall. In the NEJM paper, the overall primary cohort had a relative risk of 1.1 for autoimmune disease, which the authors described as not differing substantially between groups. The 1.5 relative risk appeared only in a secondary analysis after excluding patients with preoperative infection, cancer, or autoimmune disease. So stating flatly that thymus removal produced a 1.5-fold increase in autoimmune diseases overstates and misstates the main finding.
1 source
- Health Consequences of Thymus Removal in Adults - PMC
Although the risk of autoimmune disease did not differ substantially between the groups in the overall primary cohort (relative risk, 1.1; 95% CI, 0.8 to 1.4), a difference was found when patients with preoperative infection, cancer, or autoimmune disease were excluded from the analysis (12.3% vs. 7.9%; relative risk, 1.5; 95% CI, 1.02 to 2.2).
ablation of β-klotho, the obligatory co-receptor for FOXN1, accelerated thymic aging.
β-Klotho is not an obligatory co-receptor for FOXN1. It is the obligate co-receptor for FGF21.
Full reasoning
This mixes up two different molecules. FOXN1 is a transcription factor important for thymic epithelial cell biology. β-Klotho (KLB) is a co-receptor used in endocrine FGF signalling, including FGF21 signalling. The very Nature Aging paper cited here states that β-klotho is "the obligatory co-receptor for FGF21" in Foxn1+ thymic epithelial cells. A review in Nature Reviews Nephrology likewise describes βKlotho as an essential/obligate co-receptor for FGF21. So the article incorrectly identifies β-klotho as a co-receptor for FOXN1.
2 sources
- Enhanced paracrine action of FGF21 in stromal cells delays thymic aging | Nature Aging
Ablation of β-klotho, the obligatory co-receptor for FGF21 in Foxn1+ TECs, accelerated thymic aging, suggesting regulation of TECs by FGF21 is partially required for thymic lymphopoiesis.
- The Klotho proteins in health and disease | Nature Reviews Nephrology
βKlotho is required for metabolic activity of fibroblast growth factor 21... βKlotho forms complexes with FGFR1c and functions as the obligate co-receptor for FGF21.
A parallel relationship for survival was seen for other types of cancer including melanoma, breast, and kidney with a 44% lower risk among high thymic scores (Figure).
The cited Nature paper did not report a 44% lower-risk estimate for the melanoma/breast/renal pan-cancer analysis. The paper’s 44% figure refers to a different NSCLC subgroup.
Full reasoning
The 44% number is misplaced here. In the Nature paper, the pan-cancer section says lower risks of death were seen across cancer types and that significance was reached for melanoma, breast cancer, renal cancer, and pooled smaller types. But the paper does not report a single '44% lower risk' estimate for that melanoma/breast/renal analysis. The paper's explicit 44% figure appears elsewhere: it refers to patients with NSCLC whose tumors had PD-L1 expression below 1%, where high thymic health was associated with a 44% lower risk of progression on immunotherapy. So this sentence assigns that 44% value to the wrong result.
1 source
- Thymic health and immunotherapy outcomes in patients with cancer | Nature
Notably, among patients with the lowest PD-L1 expression (less than 1%), those who had high thymic health had a 44% lower risk of progression following immune checkpoint inhibitor therapy... We found lower risks of death in patients with average or high thymic health than in those with low thymic health across all examined cancer types, and significance was reached for patients with melanoma, breast cancer, renal cancer and pooled smaller types.