Risk factors for lower urinary tract injury at the time of hysterectomy for benign reasons

DISCLOSURES: None of the authors has any conflicts of interest to report except for Dr. Rebecca G. Rogers, who is DSMB chair for American Medical Systems Transform Trial, UptoDate royalties, ACOG royalties, and is on the executive board of the ACOG. Dr. Gena Dunivan is a member of the AUGS Education Committee. OBJECTIVE: To identify risk factors associated with lower urinary tract injury at the time of performing hysterectomy for benign indications. METHODS: We conducted a multi-center case–control study of women undergoing hysterectomy for benign disease. Cases were identified via ICD-9 codes for lower urinary tract injury at the time of hysterectomy from 2007 to 2011: controls were two subsequent hysterectomies following the index case in the same institution that did not have lower urinary tract injury. Logistic regression was used to perform univariate and multivariate comparisons between groups. RESULTS: At 7 centers, 135 cases and 270 controls were identified. Cases comprised 118 bladder injures and 25 ureteral injuries: 8 women had both bladder and ureteral injury. Bladder injury was associated with a history of prior cesarean section OR 2.9 (95% CI 1.7–5), surgery by a general obstetrician and gynecologist OR 2.4 (95% CI 1.2–5.2), and total abdominal hysterectomy OR 1.9 (95% CI 1.06–3.4). Ureteral injury was more likely among women who underwent laparoscopic-assisted vaginal hysterectomy (LAVH) OR 10.4 (95% CI 2.3–46.6) and total abdominal hysterectomy (TAH) OR 4.7 (95% CI 1.4–15.6). CONCLUSION: Bladder injury at the time of benign hysterectomy is associated with a prior history of Cesarean section and TAH as well as surgery by generalist OB-GYN; ureteral injury is associated with LAVH and TAH

Cytokine mediated liberation of soluble Fractalkine (sCX3CL1) in Human Astrocytes is dependent on ADAM10 and p38/NF-κB signalling.

The fractalkine ligand (CX3CL1) is expressed in astrocytes and reported to be neuro-protective. When cleaved from the membrane, soluble fractalkine (sCX3CL1) activates the receptor CX3CR1, which is expressed in neurons and microglia. The membrane bound form of CX3CR1 additionally acts as an adhesion molecule for microglia and infiltrating white blood cells. Here, the mechanisms involved in the up-regulation and cleavage of CX3CL1 from human astrocytes was investigated. A combination of ADAM17 (TACE) and ADAM10 protease inhibitors were found to attenuate IL-1β, TNFα and IFNγ induced sCX3CL1 levels in astrocytes. A specific ADAM10 (but not ADAM17) inhibitor also attenuated these effects, suggesting ADAM10 proteases induce release of sCX3CL1 from stimulated human astrocytes. A p38 MAPK inhibitor also attenuated the levels of sCX3CL1 upon treatment with IL-1β, TNFα or IFNγ. In addition, IKKα and IKKβ inhibitors significantly reduced the levels of sCX3CL1 induced by IL-1β or TNFα in a concentration dependent manner, suggesting a role for the NF-κB pathway. These findings are important for understanding the role of CX3CL1 in healthy and stimulated astrocytes and may benefit our understanding of this pathway in neuro-inflammatory and neurodegenerative diseases