Cushing's Syndrome Is Associated With Early Medical- and Surgical-Related Complications Following Total Joint Arthroplasty: A National Database Study.

BACKGROUND: Cushing's syndrome (CS) is a disorder characterized by exposure to supraphysiologic levels of glucocorticoids. The purpose of this study was to evaluate the association between CS and postoperative complication rates following total joint arthroplasty (TJA). METHODS: Patients diagnosed with CS undergoing TJA for degenerative etiologies were identified from a large national database and matched 1:5 to a control cohort using propensity scoring. Propensity score matching resulted in 1,059 total hip arthroplasty (THA) patients with CS matched to 5,295 control THA patients and 1,561 total knee arthroplasty (TKA) patients with CS matched to 7,805 control TKA patients. Rates of medical complications occurring within 90 days of TJA and surgical-related complications occurring within 1 year of TJA were compared using odds ratios (ORs). RESULTS: The THA patients with CS had higher incidences of pulmonary embolism (OR 2.21, P = .0026), urinary tract infection (UTI) (OR 1.29, P = .0417), pneumonia (OR 1.58, P = .0071), sepsis (OR 1.89, P = .0134), periprosthetic joint infection (OR 1.45, P = .0109), and all-cause revision surgery (OR 1.54, P = .0036). The TKA patients with CS had significantly higher incidences of UTI (OR 1.34, P = .0044), pneumonia (OR 1.62, P = .0042), and dislocation (OR 2.43, P = .0049) and a lower incidence of manipulation under anesthesia (MUA) (OR 0.63, P = .0027). CONCLUSION: CS is associated with early medical- and surgical-related complications following TJA and a reduced incidence of MUA following TKA.

Differential use of Erk1/2 and transforming growth factor beta pathways by mid- and late-gestational murine fibroblasts.

BACKGROUND: Previously, we demonstrated the rapid closure of mid-gestational excisional murine wounds at 32 hours. In this study, we theorized that mid-gestational wounds would be completely regenerated, whereas late-gestational wounds would heal with scar formation at 48 hours. Furthermore, we theorized that mid- and late-gestational fibroblasts differentially use the transforming growth factor beta and mitogen-activated protein kinase pathways. METHODS: Three-millimeter excisional cutaneous wounds were made on murine mid- (embryonic day 15 [E15]) and late-gestational (E18) fetuses and harvested at 48 hours for histology. Percent wound closure was calculated. E15 and E18 fibroblasts were cultured overnight for in vitro scratch wound assay in the presence of the activin receptor-like kinase 4-5-7, Erk1/2, and p38 inhibitors. RESULTS: E15 wounds healed in a regenerative manner, whereas E18 wounds exhibited scar formation. In vitro scratch closure was similar in the E15 and E18 groups at 8 hours; yet, it increased in E15 compared with E18 groups with activin receptor-like kinase 4-5-7 and Erk1/2 inhibitors. p38 inhibition resulted in reduced scratch closure in both groups. CONCLUSION: The scarless mid-gestational excisional wounds compared with the scar-forming late-gestational wounds provides a model to study scar formation. This study also suggests that variable transforming growth factor beta and Erk1/2 signaling may influence differences in wound closure between mid- and late-gestational wounds.

Rapid closure of midgestational excisional wounds in a fetal mouse model is associated with altered transforming growth factor-beta isoform and receptor expression.

BACKGROUND: Many pediatric diseases are characterized by excessive tissue contraction. Because of a poor understanding of contraction, few therapies exist. We developed a murine fetal excisional wound model of contraction and theorize that wound closure is associated with changes in transforming growth factor-beta (TGF-beta) expression. METHODS: Pregnant FVB mice underwent hysterotomy at midgestational (E15) or late-gestational (E18) ages. Three-millimeter excisional wounds were made in fetuses and harvested at 32 hours. Real-time polymerase chain reaction was performed for TGF-beta1, TGF-beta2, TGF-beta3, TbetaR-1, and TbetaR-2 in wounds and normal skin and normalized to glyceraldehyde-3-phosphate dehydrogenase. Data were analyzed by paired t test (P < .05). H&E staining of wounds was performed. RESULTS: E15 wounds (80.5% +/- 4.4%) were smaller than E18 wounds (10.4% +/- 10.5%; P < .001) at 32 hours. E15 wounds expressed higher levels of TGF-beta1 compared with normal skin (P = .001). TbetaR-2 levels were elevated in E15 and E18 wounds compared with their respective normal skin (P = .02, P = .01) and in E18 normal skin compared with E15 normal skin (P = .002). CONCLUSION: This study demonstrates that rapid midgestational wound closure in a murine model is associated with increased TGF-beta1 and TbetaR-2 expression. Elucidating the role of the TGF-beta pathways may lead to an improved understanding of wound contraction.