Keratinocyte growth factor (KGF) is a member of the fibroblast growth factor family that mediates epithelial cell proliferation and differentiation in a variety of tissues, including the thymus. We studied the role of KGF in T-cell development with KGF ؊/؊ mice and demonstrated that thymic cellularity and the distribution of thymocyte subsets among KGF ؊/؊ , wildtype (WT), and KGF ؉/؊ mice were similar. However, KGF ؊/؊ mice are more vulnerable to sublethal irradiation (450 cGy), and a significant decrease was found in thymic cellularity after irradiation. Defective thymopoiesis and peripheral T-cell reconstitution were found in KGF ؊/؊ recipients of syngeneic or allogeneic bone marrow transplant, but using KGF ؊/؊ mice as a donor did not affect T-cell development after transplantation. Despite causing an early developmental block in the thymus, administration of KGF to young and old mice enhanced thymopoiesis. Exogenous KGF also accelerated thymic recovery after irradiation, cyclophosphamide, and dexamethasone treatment. IntroductionKeratinocyte growth factor (KGF) is a 28-kDa fibroblast growth factor family member (FGF-7) that mediates epithelial cell proliferation and differentiation in a variety of tissues, including the gut (gut epithelial cells), skin (keratinocytes), and thymus (thymic epithelial cells). [1][2][3] KGF is produced by mesenchymal cells and has a paracrine effect on epithelial cells 4,5 ; it binds FGFR2IIIb, a splice variant of FGF receptor 2, expressed predominantly on these cell types. FGFR2IIIb is activated by 4 known ligands: FGF-1, FGF3, 7 The heterogeneous stromal cell compartment of the thymus includes both cortical and medullary epithelial cells, as well as mesenchymal cells (including fibroblasts). Mesenchymal cells produce fibroblast growth factors and support thymocyte development, especially in cortical areas (reviewed in Anderson and Jenkinson 8 ). Jenkinson et al 9 reported that mesenchymal cells regulate the proliferation of thymic epithelial cells via the production of KGF (FGF-7) and fibroblast growth factor-10 (FGF-10) during fetal development, but the role of mesenchymal cells in regulating the composition of thymic stroma in the neonatal and postnatal period is unclear.Erikson et al 10 have demonstrated that KGF and FGFR2IIIb signaling can affect the development and function of thymic epithelium (TE). In the adult thymus, mature ␣␤ ϩ thymocytes are capable of producing KGF, which leads to the expansion of thymic medullary epithelial cells. 10 However, KGF expression is not detectable in the triple negative (CD3 Ϫ CD4 Ϫ CD8 Ϫ ) thymocyte precursors. 10 In contrast, peripheral ␣␤ Ϫ T cells do not secrete KGF, even in epithelial tissues that comprise the skin, intestine, and vagina. However, ␥␦ Ϫ T cells in epithelial tissues do produce KGF and may also regulate epithelial cell growth. 11 KGF can function as a growth factor for epithelial protection and repair, is found in a variety of tissues (extensively reviewed by Finch and Rubin 12 ), and is up-regulated after various ...

Background: Coronary artery bypass graft (CABG) surgery is the most widely performed cardiac surgery in the United States. Transesophageal echocardiography (TEE) is frequently used in a variety of cardiac surgical procedures, but its clinical benefit in isolated CABG surgery is unclear, and guidelines remain indeterminate. The aim of this study was to compare clinical outcomes among patients undergoing isolated CABG surgery with versus without TEE in order to test the hypothesis that TEE would be associated with improved clinical outcomes after CABG surgery.Methods: A matched retrospective cohort study was conducted among Medicare beneficiaries undergoing isolated CABG surgery with versus without intraoperative monitoring using TEE in the United States. The primary analysis was a near/far instrumental variable match that paired hospitals with similar characteristics and patient populations but with opposing probabilities for using TEE in CABG surgery. Outcomes included 30-day mortality, a composite outcome of stroke or 30-day mortality, length of hospitalization, and incidence of esophageal perforation.Results: Of 114,871 patients undergoing isolated CABG surgery, 65,471 (57%) underwent TEE and 49,400 (43%) did not. Hospital-level instrumental variable matched analysis demonstrated that among the subset of 968 matched hospitals, TEE receipt was associated with lower 30-day mortality (3.7% vs 4.9%, P < .001), a lower incidence of the composite outcome of stroke or 30-day mortality (4.5% vs 5.6%, P < .001), no difference in length of hospitalization (10.32 vs 10.52 days, P = .26), and no difference in the incidence of esophageal perforation (0.01% vs 0.01%, P = .63). These results were replicated in surgeon-level and patient-level matched-pair instrumental variable analyses, and all analyses were robust to sensitivity analyses that tested for biases introduced by unmeasured confounding. Conclusions:The findings from this study suggest that TEE may offer a clinical benefit to cardiac surgical patients undergoing isolated CABG surgery.

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