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Wake Forest, NC, United States

Kempton S.J.,University of Wisconsin - Madison | Cho D.C.,Straub Clinic and Hospital | Thimmappa B.,Wake Forest Medical Center | Martin M.C.,Loma Linda University
Annals of Plastic Surgery | Year: 2016

Background: Current trends in the management of medial orbital wall fractures are toward the development of transconjunctival incisions and the use of endoscopic-assisted methods. Different authors have suggested variations of the medial transconjunctival approach. Methods: (1) In 30 fresh cadaver orbits, the classic transcaruncular approach was compared with the precaruncular and retrocaruncular approach under magnified dissection. (2) A retrospective analysis was conducted on a series of 20 consecutive patients that underwent primary repair of medial orbital wall fractures using a retrocaruncular approach without endoscopic assistance. Postoperative computed tomography scanswere obtained for all patients andwere evaluated by 3 experienced clinicians. Results: (1) Anatomic dissections showed that all 3 approaches provided excellent exposure of the entire medial orbital wall. The transcaruncular and precaruncular approaches, however, (a) both resulted in exposure of the upper and lower tarsi when incisions greater than 10 mm were used; (b) both required a transition from the preseptal plane to the postseptal plane when combined with inferior fornix incisions. (2) A clinical study of 20 patients showed all reconstructions were possible without endoscopic assistance, resulting in no postoperative complications. Postoperative computed tomography scans showed anatomic orbital reconstruction in all patients judged as excellent by the clinicians. Conclusions: Medial orbital wall fractures can be successfully repaired using transconjunctival incisions without using endoscopes. The retrocaruncular approach surpasses the transcaruncular and precaruncular methods due to its decreased risk of postoperative lid complications and its ability to be directly carried to the inferior conjunctival fornix. © 2016 Wolters Kluwer Health, Inc. All rights reserved.

Novotna M.,Rochester College | Novotna M.,St Annes University Hospital Brno | Paz Soldan M.M.,Rochester College | Zeid N.A.,Wake Forest Medical Center | And 13 more authors.
Neurology | Year: 2015

Objective: To evaluate the relationship between early relapse recovery and onset of progressive multiple sclerosis (MS). Methods: We studied a population-based cohort (105 patients with relapsing-remitting MS, 86 with bout-onset progressive MS) and a clinic-based cohort (415 patients with bout-onset progressive MS), excluding patients with primary progressive MS. Bout-onset progressive MS includes patients with single-attack progressive and secondary progressive MS. "Good recovery" (as opposed to "poor recovery") was assigned if the peak deficit of the relapse improved completely or almost completely (patient-reported and examination-confirmed outcome measured $6 months post relapse). Impact of initial relapse recovery and first 5-year average relapse recovery on cumulative incidence of progressive MS was studied accounting for patients yet to develop progressive MS in the population-based cohort (Kaplan-Meier analyses). Impact of initial relapse recovery on time to progressive MS onset was also studied in the clinic-based cohort with already-established progressive MS (t test). Results: In the population-based cohort, 153 patients (80.1%) had on average good recovery from first 5-year relapses, whereas 30 patients (15.7%) had on average poor recovery. Half of the good recoverers developed progressive MS by 30.2 years after MS onset, whereas half of the poor recoverers developed progressive MS by 8.3 years after MS onset (p = 0.001). In the clinic-based cohort, good recovery from the first relapse alone was also associated with a delay in progressive disease onset (p < 0.001). A brainstem, cerebellar, or spinal cord syndrome (p = 0.001) or a fulminant relapse (p < 0.0001) was associated with a poor recovery from the initial relapse. Conclusions: Patients with MS with poor recovery from early relapses will develop progressive disease course earlier than those with good recovery. © 2015 American Academy of Neurology.

Mullany S.A.,Wake Forest Medical Center | Moslemi-Kebria M.,Mayo Medical School | Rattan R.,Mayo Medical School | Khurana A.,Mayo Medical School | And 6 more authors.
Clinical Cancer Research | Year: 2011

Purpose: The purpose of this study was to determine if loss of serine protease HtrA1 in endometrial cancer will promote the invasive potential of EC cell lines. Experimental design: Western blot analysis and immunohistochemistry methods were used to determine HtrA1 expression in EC cell lines and primary tumors, respectively. Migration, invasion assays and in vivo xenograft experiment were performed to compare the extent of metastasis between HtrA1 expressing and HtrA1 knocked down clones. Results: Western blot analysis of HtrA1 in 13 EC cell lines revealed complete loss of HtrA1 expression in all seven papillary serous EC cell lines. Downregulation of HtrA1 in Hec1A and Hec1B cell lines resulted in a three- to fourfold increase in the invasive potential. Exogenous expression of HtrA1 in Ark1 and Ark2 cells resulted in three- to fourfold decrease in both invasive and migration potential of these cells. There was an increased rate of metastasis to the lungs associated with HtrA1 downregulation in Hec1B cells compared to control cells with endogenous HtrA1 expression. Enhanced expression of HtrA1 in Ark2 cells resulted in significantly less tumor nodules metastasizing to the lungs compared to parental or protease deficient (SA mutant) Ark2 cells. Immunohistochemical analysis showed 57% (105/184) of primary EC tumors had low HtrA1 expression. The association of low HtrA1 expression with high-grade endometrioid tumors was statistically significant (P = 0.016). Conclusions: Collectively, these data indicate loss of HtrA1 may contribute to the aggressiveness and metastatic ability of endometrial tumors. ©2010 AACR.

Nabors L.B.,University of Alabama at Birmingham | Mikkelsen T.,Ford Motor Company | Hegi M.E.,University of Lausanne | Ye X.,Sidney Kimmel Comprehensive Cancer Center | And 9 more authors.
Cancer | Year: 2012

Background: Cilengitide is a selective integrin inhibitor that is well tolerated and has demonstrated biologic activity in patients with recurrent malignant glioma. The primary objectives of this randomized phase 2 trial were to determine the safety and efficacy of cilengitide when combined with radiation and temozolomide for patients with newly diagnosed glioblastoma multiforme and to select a dose for comparative clinical testing. Methods: In total, 112 patients were accrued. Eighteen patients received standard radiation and temozolomide with cilengitide in a safety run-in phase followed by a randomized phase 2 trial with 94 patients assigned to either a 500 mg dose group or 2000 mg dose group. The trial was designed to estimate overall survival benefit compared with a New Approaches to Brain Tumor Therapy (NABTT) Consortium internal historic control and data from the published European Organization for Research and Treatment of Cancer (EORTC) trial EORTC 26981. Results: Cilengitide at all doses studied was well tolerated with radiation and temozolomide. The median survival was 19.7 months for all patients, 17.4 months for the patients in the 500 mg dose group, 20.8 months for patients in the 2000 mg dose group, 30 months for patients who had methylated O6-methylguanine-DNA methyltransferase (MGMT) status, and 17.4 months for patients who had unmethylated MGMT status. For patients aged ≤70 years, the median survival and survival at 24 months was superior to what was observed in the EORTC trial (20.7 months vs 14.6 months and 41% vs 27%, respectively; P =.008). Conclusions: Cilengitide was well tolerated when combined with standard chemoradiation and may improve survival for patients newly diagnosed with glioblastoma multiforme regardless of MGMT methylation status. The authors concluded that, from an efficacy and safety standpoint, future trials of this agent in this population should use the 2000 mg dose. © 2012 American Cancer Society.

Clarke M.J.,Mayo Medical School | Zadnik P.L.,Johns Hopkins University | Groves M.L.,Johns Hopkins University | Dasenbrock H.H.,Brigham and Womens Hospital | And 6 more authors.
Journal of Neurosurgery: Spine | Year: 2014

Object. Traditionally, hemisacrectomy and internal hemipelvectomy procedures have required both an anterior and a posterior approach. A posterior-only approach has the potential to complete an en bloc tumor resection and spinopelvic reconstruction while reducing surgical morbidity. Methods. The authors describe 3 cases in which en bloc resection of the hemisacrum and ilium and subsequent lumbopelvic and pelvic ring reconstruction were performed from a posterior-only approach. Two more traditional anterior and posterior staged procedures are also included for comparison. Results. In all 3 cases, an oncologically appropriate surgery and spinopelvic reconstruction were performed through a posterior-only approach. Conclusions. The advantage of a midline posterior approach is the ability to perform a lumbosacral reconstruction, necessary in cases in which the S-1 body is iatrogenically disrupted during tumor resection. © 2014 AANS.

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