Patients refractory to first-line therapy or who relapse within 12 months of receiving salvage therapy (including bone marrow transplant) for recurrent disease have had poor prognoses with median overall survival rates of 3.3 and 6.3 months, respectively. The prognosis of these patients appears to be improved by using CAR-T therapy. Chimeric antigen receptor T cell (i.e. CAR-T) adoptive cellular immunotherapy has emerged as a recent advance in treating refractory and relapsed DLBCL, NOS (tisagenlecleucel, axicabtagene ciloleucel, lisocabtagene maraleucel). Chimeric antigen receptor T cells are genetically engineered to express: 1) an artificial T-cell receptor consisting of antigen-recognition and attached hinge domains expressed on their surface membranes; 2) a surface membrane-spanning domain; 3) an intracellular domain which, when the antigen-recognition domain binds its targeted antigen, activates signaling pathways that cause the T-cell to attack and kill cells that bear the recognized antigen on their surface membranes; and 4), in more recently devised second generation CAR-T strategies, an associated intracellular co-stimulating molecule (e.g. CD28 or 4-1BB) which augments activation of the cell-killing signaling pathways. CAR-T therapy, as it pertains to DLBCL, NOS, kills a patients neoplastic B-cells by isolating this patients T-cells; genetically engineering these cells to express an artificial T-cell receptor designed to bind an antigen expressed on the surface of their neoplastic B-cells; and infusing these cells back into the donor patient. The targeted antigen has usually been CD19, a surface membrane protein expressed on virtually all B-cells including the neoplastic cells in DLBCL, NOS.
The FDA has issued several letters warning manufacturers and suppliers of colon hydrotherapy equipment about making false claims of effectiveness, safety issues, and quality control violations. History
The concept of autointoxication, the idea that food enters the intestine and rots, provides a rationale for colon cleansing. The ancient Egyptians believed that toxins formed as a result of decomposition within the intestines, and moved from there into the circulatory system, causing fever and the development of pus. The Ancient Greeks adopted and expanded the idea, applying their belief in the four humours. In the 19th century, studies in biochemistry and microbiology seemed to support the autointoxication hypothesis, and mainstream physicians promoted the idea. Daly notes that, historically, "purging was one of the few procedures that a physician could perform with visible, often impressive results and without immediate or obvious dangers".Ilya Ilyich Mechnikov (1845-1916) became the strongest supporter of the idea of colon cleansing; he thought that toxins could shorten the lifespan. Over time, the concept broadened to autointoxication, which supposes that the body cannot fully dispose of its waste products and toxins, which then accumulate in the intestine. In some cases, the concept led to radical surgeries to remove the colon for unrelated symptoms.Autointoxication enjoyed some favor in the medical community in the late 19th and early 20th centuries, but clinicians discarded it as advances in science failed to support its claims.