Citations

AbstractScaffolds with porous structures are highly applicable for tissue engineering and regenerative medicine. In the present study, 3‐dimensional poly(propylene fumarate‐co‐caprolactone) [P(PF‐co‐CL)] scaffolds were fabricated from a P(PF‐co‐CL)–dioxane‐water ternary system through thermally induced phase separation (TIPS). Cloud points of P(PF‐co‐CL) in dioxane‐water solutions increased with increased solute concentration, but increased dioxane composition decreased cloud point. Among 3 polymer concentrations (4, 8, and 12 wt%), 8 wt% P(PF‐co‐CL) scaffolds exhibited the best pore interconnectivity, with large, regular sized pores. Scaffolds were formed in 3 solutions with different dioxane‐water ratios (74/26, 78/22, and 82/18 wt/wt); the 78/22 wt/wt scaffold had finger‐shaped patterns with better interconnectivity than scaffolds from the other two ratios. Higher dioxane‐water ratios resulted in a larger contact angle and thus less wettability for the fabricated scaffold, while scaffolds fabricated from higher concentrations of P(PF‐co‐CL) or high dioxane‐water ratios had better biomineralization after soaking in simulated body fluid. In vitro cell viability testing showed the scaffolds had good biocompatibility with both bone and nerve cells. The results indicate that the polymer concentration and solvents ratio significantly affect the formation of porous structures, and optimum processing parameters were found to be 8% polymer concentration and 22% to 24% water content. These porous P(PF‐co‐CL) scaffolds fabricated via TIPS may be useful in various tissue engineering applications © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 226–235, 2017.

Abstract BACKGROUND: The optimum treatment for cystic vestibular schwannoma (VS) remains controversial. Anecdotally, many treating physicians feel that cystic VSs do not respond to stereotactic radiosurgery (SRS) as well as noncystic tumors. OBJECTIVE: To present outcomes after treatment of predominantly cystic VS with SRS. METHODS: A prospectively maintained clinical database of patients undergoing Gamma Knife (Elekta Instruments, Stockholm, Sweden) radiosurgery (GKRS) for VS at a single tertiary academic referral center was retrospectively reviewed. Patients diagnosed with cystic VS who were treated with GKRS between 1997 and 2014 were analyzed. Size-matched solid tumors treated with GKRS during this period were selected as controls. RESULTS: Twenty patients (12 women; median age at treatment, 56 years; range, 36-85 years) with cystic VS met inclusion criteria. The median radiologic follow-up within the cystic group was 63 months (range, 17-201 months), and the median change in tumor size was −4.9 mm (range, −10.4 to 9.3 mm). Sixteen tumors (80%) shrank, 2 (10%) remained stable, and 2 (10%) enlarged, accounting for a tumor control rate of 90%. The median radiologic follow-up in the noncystic control group was 67 months (range, 6-141 months), and the median change in size was −2.0 mm (range, −10.4 to 2.5 mm). Tumor control in the solid group was 90%. Comparing only those tumors that decreased in size showed that there was a trend toward a greater reduction within the cystic group ( P = .05). CONCLUSION: The present study demonstrates that tumor control after SRS for cystic VS may not differ from that of noncystic VS in selected cases.

AbstractBackgroundGlioblastoma (GBM) exhibits profound intratumoral genetic heterogeneity. Each tumor comprises multiple genetically distinct clonal populations with different therapeutic sensitivities. This has implications for targeted therapy and genetically informed paradigms. Contrast-enhanced (CE)-MRI and conventional sampling techniques have failed to resolve this heterogeneity, particularly for nonenhancing tumor populations. This study explores the feasibility of using multiparametric MRI and texture analysis to characterize regional genetic heterogeneity throughout MRI-enhancing and nonenhancing tumor segments.MethodsWe collected multiple image-guided biopsies from primary GBM patients throughout regions of enhancement (ENH) and nonenhancing parenchyma (so called brain-around-tumor, [BAT]). For each biopsy, we analyzed DNA copy number variants for core GBM driver genes reported by The Cancer Genome Atlas. We co-registered biopsy locations with MRI and texture maps to correlate regional genetic status with spatially matched imaging measurements. We also built multivariate predictive decision-tree models for each GBM driver gene and validated accuracies using leave-one-out-cross-validation (LOOCV).ResultsWe collected 48 biopsies (13 tumors) and identified significant imaging correlations (univariate analysis) for 6 driver genes: EGFR, PDGFRA, PTEN, CDKN2A, RB1, and TP53. Predictive model accuracies (on LOOCV) varied by driver gene of interest. Highest accuracies were observed for PDGFRA (77.1%), EGFR (75%), CDKN2A (87.5%), and RB1 (87.5%), while lowest accuracy was observed in TP53 (37.5%). Models for 4 driver genes (EGFR, RB1, CDKN2A, and PTEN) showed higher accuracy in BAT samples (n = 16) compared with those from ENH segments (n = 32).ConclusionMRI and texture analysis can help characterize regional genetic heterogeneity, which offers potential diagnostic value under the paradigm of individualized oncology.

Hyperglycemia control is associated with improved outcomes in patients undergoing cardiac surgery. The Surgical Care Improvement Project metric (SCIP-inf-4) was introduced as a performance measure in surgical patients and included hyperglycemia control. Compliance with the SCIP-inf-4 metric remains suboptimal. A novel real-time decision support tool (DST) with guaranteed feedback that is based on the existing electronic medical record system was developed at a tertiary academic center. Implementation of the DST increased the compliance rate with the SCIP-inf-4 from 87.3% to 96.5%. Changes in tested clinical outcomes were not observed with improved metric compliance. This new framework can serve as a backbone for development of quality control processes for other metrics. Further and, ideally, multicenter studies are required to test if implementation of electronic DSTs will translate into improved resource utilization and outcomes for patients.

Objectives To describe the clinicopathological features associated with increased risk of renal fossa recurrence ( RFR ) after radical nephrectomy ( RN ) and to describe the prognostic features associated with cancer‐specific survival ( CSS ) among patients with RFR treated with primary locally directed therapy, systemically directed therapy or expectant management. Patients and Methods The records of 2 502 patients treated with RN for unilateral, sporadic, localized renal cell carcinoma ( RCC ) between 1970 and 2006 were reviewed. CSS after RFR was estimated using the Kaplan–Meier method. Associations with the development of RFR and CSS after RFR were evaluated using Cox proportional hazards regression models. Results A total of 33 (1.3%) patients developed isolated RFR ( iRFR ) and 30 (1.2%) patients developed RFR in the setting of synchronous metastases after RN (study cohort, N = 63). The median follow‐up for the series was 9.0 years after RN and 6.0 years after RFR diagnosis. On multivariable analysis, advanced pathological stage ( pT 2: hazard ratio [ HR ] 4.36, P = 0.004; pT 3/4: HR 4.39, P = 0.003) and coagulative necrosis ( HR 2.71, P = 0.006) were independently associated with increased risk of iRFR . The median time to recurrence was 1.5 years after RN among the 33 patients with iRFR , and 1.4 years among all patients. Overall, the median CSS was 2.5 years after diagnosis of iRFR , 1.3 years after RFR in the setting of synchronous metastases, and 2.2 years overall. After primary locally directed therapy (surgery, ablation or radiation), systemic therapy or expectant management, the 3‐year CSS rates among patients with iRFR were 63%, 50% and 13% ( P = 0.001) and were 64%, 50% and 28% ( P = 0.006) among all patients, respectively. On multivariable analysis, when compared with observation, locally directed therapies were associated with a significantly decreased risk of death from RCC ( HR 0.26, P < 0.001). Conclusions Renal fossa recurrence is a rare event after RN for RCC and portends a poor prognosis, even in the absence of synchronous metastases. Development of iRFR is associated with advanced stage and aggressive tumour biology. Patients who underwent primary locally directed therapy had superior CSS compared with those treated with expectant management, supporting the use of aggressive local treatment in carefully selected patients with RFR . Future research is needed to determine the optimum role and sequencing of combined therapy in patients with this rare entity.

SummaryBackgroundRefractory coeliac disease is a severe complication of coeliac disease with heterogeneous outcome.AimTo create a prognostic model to estimate survival of patients with refractory coeliac disease.MethodsWe evaluated predictors of 5‐year mortality using Cox proportional hazards regression on subjects from a multinational registry. Bootstrap resampling was used to internally validate the individual factors and overall model performance. The mean of the estimated regression coefficients from 400 bootstrap models was used to derive a risk score for 5‐year mortality.ResultsThe multinational cohort was composed of 232 patients diagnosed with refractory coeliac disease across seven centres (range of 11–63 cases per centre). The median age was 53 years and 150 (64%) were women. A total of 51 subjects died during a 5‐year follow‐up (cumulative 5‐year all‐cause mortality = 30%). From a multiple variable Cox proportional hazards model, the following variables were significantly associated with 5‐year mortality: age at refractory coeliac disease diagnosis (per 20 year increase, hazard ratio = 2.21; 95% confidence interval, CI: 1.38–3.55), abnormal intraepithelial lymphocytes (hazard ratio = 2.85; 95% CI: 1.22–6.62), and albumin (per 0.5 unit increase, hazard ratio = 0.72; 95% CI: 0.61–0.85). A simple weighted three‐factor risk score was created to estimate 5‐year survival.ConclusionsUsing data from a multinational registry and previously reported risk factors, we create a prognostic model to predict 5‐year mortality among patients with refractory coeliac disease. This new model may help clinicians to guide treatment and follow‐up.

Background: Knee laxity in the setting of suspected anterior cruciate ligament (ACL) injury is frequently assessed through physical examination using the Lachman, pivot-shift, and anterior drawer tests. The degree of laxity noted on these examinations may influence treatment decisions and prognosis. Hypothesis: Increased preoperative knee laxity would be associated with increased risk of subsequent revision ACL reconstruction and worse patient-reported outcomes 2 years postoperatively. Study Design: Cohort study; Level of evidence, 2. Methods: From an ongoing prospective cohort study, 2333 patients who underwent primary isolated ACL reconstruction without collateral or posterior cruciate ligament injury were identified. Patients reported by the operating surgeons as having an International Knee Documentation Committee (IKDC) grade D for Lachman, anterior drawer, or pivot-shift examination were classified as having high-grade laxity. Multiple logistic regression modeling was used to evaluate whether having high-grade preoperative laxity was associated with increased odds of undergoing revision ACL reconstruction within 2 years of the index procedure, controlling for patient age, sex, Marx activity level, level of competition, and graft type. Multiple linear regression modeling was used to evaluate whether having high-grade preoperative laxity was associated with worse IKDC score or Knee injury and Osteoarthritis Outcome Score Knee-Related Quality of Life subscale (KOOS-QOL) scores at a minimum 2 years postoperatively, controlling for baseline score, patient age, ethnicity, sex, body mass index, marital status, smoking status, sport participation, competition level, Marx activity rating score, graft type, and articular cartilage and meniscus status. Results: Pre-reconstruction laxity data were available for 2325 patients (99.7%). Two-year revision data were available for 2259 patients (96.8%), and patient-reported outcomes were available for 1979 patients (84.8%). High-grade preoperative laxity was noted in 743 patients (31.9%). The mean postoperative IKDC score was 81.8 ± 15.9, and the mean KOOS-QOL score was 72.0 ± 22.0. The presence of high-grade pre-reconstruction laxity was associated with significantly increased odds of ACL graft revision (odds ratio [OR] = 1.87 [95% CI, 1.19-2.95]; P = .007). The presence of high-grade pre-reconstruction laxity was not associated with any difference in postoperative IKDC (β = −0.56, P = .44) or KOOS-QOL (β = 0.04, P = .97). Conclusion: The presence of high-grade pre-reconstruction knee laxity as assessed by manual physical examination under anesthesia is associated with significantly increased odds of revision ACL surgery but has no association with patient-reported outcome scores at 2 years after ACL reconstruction.

Purpose To describe outcomes of salvage radiotherapy (SRT) for men with detectable prostate-specific antigen (PSA) after radical prostatectomy for prostate cancer and identify associations with outcomes. Patients and Methods A total of 1,106 patients received SRT between January 1987 and July 2013, with median follow-up 8.9 years. Outcomes were estimated using Kaplan-Meier for overall survival (OS) and cumulative incidence for biochemical recurrence (BcR), distant metastases (DM), and cause-specific mortality (CSM). Variable associations with outcomes used Cox or Fine-Gray methods, as appropriate. Multiple variable analyses used backward selection with P < .05 for retention. Results In multiple variable analyses, pathologic tumor stage, Gleason score, and pre-SRT PSA were associated with BcR, DM, CSM, and OS; androgen suppression and SRT doses > 68 Gy were associated with BcR; and age was associated with OS. Each pre-SRT PSA doubling increased significantly the relative risk of BcR (hazard ratio [HR], 1.30; P < .001), DM (HR, 1.32; P < .001), CSM (HR, 1.40; P < .001), and all-cause mortality (HR, 1.12; P = .02). Using a pre-SRT PSA cutoff ≤ 0.5 versus > 0.5 ng/mL, 5-year and 10-year cumulative incidences for BcR were 42% versus 56% and 60% versus 68% ( P < .001), DM 7% versus 14% and 13% versus 25% ( P < .001), CSM 1% versus 4% and 6% versus 13% ( P < .001), and OS of 94% versus 92% and 83% versus 73% ( P > .05). Conclusion SRT outcomes are in part affected by factors associated with prostatectomy findings but may be positively affected by using SRT at lower PSA levels, including reductions in BcR, DM, CSM, and all-cause mortality. These findings argue against prolonged monitoring of detectable postprostatectomy PSA levels that delay initiation of SRT.