Citations

OBJECTIVE An increasing number of patients with poor-grade aneurysmal subarachnoid hemorrhage (aSAH) have received endovascular treatment. Endovascular treatment of poor-grade aSAH, however, is based on single-center retrospective studies, and predictors of long-term outcome have not been well defined. Using results from a multicenter prospective registry, the authors aimed to develop preoperative and postoperative prognostic models to predict poor outcome after endovascular treatment of poor-grade aSAH. METHODS A Multicenter Poor-grade Aneurysm Study (AMPAS) was a prospective and observational registry of consecutive patients with poor-grade aSAH. From October 2010 to March 2012, 366 patients were enrolled in the registry, and 136 patients receiving endovascular treatment were included in this study. Outcome was assessed by modified Rankin Scale (mRS) score at 12 months, and poor outcome was defined as an mRS score of 4, 5, or 6. Prognostic models were developed in multivariate logistic regression models. The area under receiver operating characteristic curves (AUC) was used to assess the model's discriminatory ability, and Hosmer-Lemeshow goodness-of-fit tests were used to assess the calibration. RESULTS At 12 months, 64 patients (47.0%) had a poor outcome: 9 (6.6%) had an mRS score of 4, 6 (4.4%) had an mRS score of 5, and 49 (36.0%) had died. Univariate analyses showed that older age (p = 0.001), female sex (p = 0.044), lower Glasgow Coma Scale score (p < 0.001), a World Federation of Neurosurgical Societies (WFNS) grade of V (p < 0.001), higher Fisher grade (p < 0.001), modified Fisher grade (p < 0.001), and wider neck aneurysm (p = 0.026) were associated with a poor outcome. There was a trend toward a worse outcome in patients with anterior communicating artery aneurysms (p = 0.080) and in those with incompletely occluded aneurysms (p = 0.063). After endovascular treatment, the presence of cerebral infarction (p = 0.039), symptomatic vasospasm (p = 0.039), and pneumonia (p = 0.006) were associated with a poor outcome. Multivariate analyses showed that the preoperative prognostic model including age, a WFNS grade of V, modified Fisher grade, and aneurysm neck size had excellent discrimination with an AUC of 0.86 (95% CI 0.80–0.92, p < 0.001), and a postoperative model that included these predictors as well as postoperative pneumonia had excellent discrimination (AUC = 0.87, 95% CI 0.81–0.93, p < 0.001). Both models had good calibration (p = 0.941 and p = 0.653, respectively). CONCLUSIONS Older age, WFNS Grade V, higher modified Fisher grade, wider neck aneurysm, and postoperative pneumonia were independent predictors of poor outcome after endovascular treatment of poor-grade aSAH. The preoperative model had almost the same discrimination as the postoperative model. Endovascular treatment should be carefully considered in patients with poor-grade aSAH with ruptured wide-neck aneurysms. ▪ CLASSIFICATION OF EVIDENCE Type of question: prognostic; study design: retrospective cohort trial; evidence: Class I.

Interplay between cell polarity module Scribble‐Lethal Giant Larvae‐Discs Large 1 (DLG1) and Yes‐associated protein (YAP) appears critical in tumor metastasis. We identified zinc finger protein 191 (ZNF191) as a metastasis suppressor acting through DLG‐YAP crosstalk in hepatocellular carcinoma (HCC). Overexpression of ZNF191 in HCC cells impaired cell motility, while ZNF191 depletion promoted cell migration in vitro and metastasis in vivo through triggering YAP signaling. Chromatin immunoprecipitation‐sequencing revealed that ZNF191 specifically bound to the promoter of DLG1, a cell polarity maintainer and a negative regulator of YAP. The binding sequence of ZNF191 at the DLG1 promoter is a seven‐repeat of TCAT motif. Double‐knockdown experiments inferred that DLG1 was not only the mediator of the function of ZNF191 to suppress migration but also a link between ZNF191 and YAP signaling. Decreased expression of ZNF191 in human metastatic HCC specimens correlated positively with DLG1 levels but inversely with YAP activation. Our findings illustrate a YAP‐targeting, antimetastasis function of ZNF191, thereby representing a possible prognostic marker and a potential target for metastasis therapy. Conclusion: ZNF191 directly binds to the DLG1 promoter at a typical TCAT repeating motif and activates the expression of DLG1; through up‐regulating DLG1, ZNF191 inhibits cell migration and YAP activation in HCC cells and eventually inhibits metastasis. (Hepatology 2016;64:1148‐1162)

Purpose To (1) evaluate long‐term outcomes of osteochondral allograft (OCA) with regard to clinical outcome scores, reoperation and failure rates, and (2) examine if certain factors predispose patients to worse outcomes. Methods A comprehensive review was performed with specific inclusion criteria for studies with long‐term outcomes after OCA. Studies reported on patient clinical scores such as Hospital for Special Surgery score, Knee Society Score (knee and function score), and Lysholm score. Reoperation and failure rates were recorded for each study. Modified Coleman Methodology Scores assessed study methodological quality. Results Five studies with a total of 291 patients (55% male, 45% female) and average age of 34.8 years (range, 15 to 69 years) were included. Of all lesions, 67% were on the femoral condyles, 29% on the tibial plateau, and 4% were patellofemoral. All scores (Knee Society Function Score, Knee Society Knee Score, and Lysholm score) have significant mean improvement from preoperative to final follow‐up. The mean postoperative Hospital for Special Surgery score was 84.1. The mean failure rate was 25% at 12.3 years with a reoperation rate of 36%. A total of 72% of the failures were conversion to total (68%) or unicompartmental (4%) knee arthroplasty and 28% involved graft removal, graft fixation, and graft revision. Patellofemoral lesions (83%) had a significantly higher reoperation rate than lesions involving the tibial plateau or the femoral condyles (34%, P = .01). Conclusions Overall, OCA demonstrated significant improvements in clinical outcome scores and good durability with successful outcomes in 75% of the patients at 12.3 years after surgery. Patellofemoral lesions are associated with decreased clinical improvement and more frequent reoperations. The orthopaedic literature is limited by heterogeneity in surgical technique, lesion and patient characteristics, and reporting of nonstandardized outcome measures. Level of Evidence Level IV, systematic review of Level II and IV studies.