vascular calcification.pptx
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Calcification of coronary arteries is highly prevalent among chronic kidney disease (CKD) patient populations according to three studies. The percentage of CKD patients with coronary artery calcification across the studies ranged from 51% in CKD patients not on dialysis to 83% in prevalent dialysis patients. Vascular calcification is associated with increased cardiovascular risk and mortality. Non-invasive imaging such as lateral abdominal x-rays and echocardiograms can detect the presence of vascular and valvular calcification, identifying patients at highest risk. One study in Thailand found the overall prevalence of abdominal aorta calcification among CKD patients was 70.7%, with similar rates between those not on dialysis and those undergoing dialysis.
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There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
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Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Histopathology of Rheumatoid Arthritis: Visual treat
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- 1. Moe, SM et al. ACKD: 3-12, 2007
- 2. Calcification of Coronary Arteries is Highly Prevalent Among CKD Patient Populations 2 CKD = chronic kidney disease; RIND=Renagel in New Dialysis; TTG=treat-to-goal. 1. Russo D et al. Am J Nephrol. 2007;27:152-158. 2. Spiegel DM et al. Hemodial Int. 2004;8:265-272. 3. Chertow GM et al. Kidney Int. 2002;62:245-252. Percentage of CKD Patients With Coronary Artery Calcification Across 3 Studies in Different CKD Populations 51 64 83 0 20 40 60 80 100 CKD Patients Not on Dialysis Incident Dialysis Prevalent Dialysis Patients (%) (Russo1) (Spiegel, RIND2) (Chertow, TTG3)
- 3. Probability of all-cause survival according to calcification score. Jacques Blacher et al. Hypertension. 2001;38:938-942 Copyright © American Heart Association, Inc. All rights reserved.
- 5. Diagnosis of CKD-MBD: Vascular Calcification • In CKD stages 3-5D, the suggestionsa indicate that: • It is reasonable to use alternatives to computed tomography-based imaging to detect the presence or absence of vascular calcification, including: • Lateral abdominal radiograph • Echocardiogram • Patients with known vascular/valvular calcification can be considered at highest cardiovascular risk KDIGO. Kid Int. 2009; 76 (Suppl 113):S1-S130
- 6. KDIGO2 KDOQI1 Patients with known vascular/valvular calcification (2A) – Considered at highest cardiovascular risk It is reasonable to use this information to guide the management of CKD-MBD (not graded) Detecting presence/absence of valvular calcification in CKD stages 3-5D (2C) – Lateral abdominal X-ray to detect presence/absence of vascular calcification – Echocardiogram detect presence/ absence of valvular calcification Recommendations for Vascular Calcification • Calcification screening • No recommendation • Dialysis patients with severe vascular calcification and/or other soft-tissue calcification • Non-calcium-containing phosphate binders are preferred 1. National Kidney Foundation (NKF). KDOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. Am J Kidney Dis. 2003;42(4 suppl 3):S1-S201. 2. Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD) Kidney Int. 2009;76(suppl 113):S1-S130.
- 8. Arterial Calcification on Plain X-rays
- 10. Figure 1 Kidney International 2008 74, 1505-1507DOI: (10.1038/ki.2008.503) Copyright © 2008 International Society of Nephrology Terms and Conditions Kidney International (2008) 74, 1505–1507. Cardiovascular risk in dialysis patients: an X-ray vision on vascular calcifications Teresa Adragão1 and João M. Frazão2
- 11. Prevalence of Abdominal Aorta Calcification (AAC) in Thai CKD patients Lumlertgul, Dusit, et al. "Prevalence of and Predictive Factor for Abdominal Aortic Calcification in Thai Chronic Kidney Disease Patients." Therapeutic Apheresis ● In this study done in Thailand, the overall prevalence of the presence of Abdominal Aorta Calcification (AAC), as defined by a score of ≥1, was 70.7%. ● By treatment status, AAC was prevalent at 70.6% and at 70.8% for patients not on dialysis and patients undergoing dialysis, respectively.