Citations

PURPOSE: We have completed a phase I study, followed by three phase I/II studies, in patients with metastatic melanoma, renal cell carcinoma (RCC), and sarcoma in order to evaluate the safety, toxicity, and antitumor activity of Leuvectin (Vical Inc, San Diego, CA), a gene transfer product containing a plasmid encoding human interleukin (IL)-2 formulated with the cationic lipid 1,2-dimyristyloxypropyl-3-dimethyl-hydroxyethyl ammonium bromide/dioleyl-phosphatidyl-ethanolamine (DMRIE/DOPE) and administered intratumorally. PATIENTS AND METHODS: Twenty-four patients were treated in the phase I study. Leuvectin doses were 10 μg, 30 μg, or 300 μg weekly for 6 weeks. In three subsequent phase I/II studies, a total of 52 patients (18 with melanoma, 17 with RCC, and 17 with sarcoma) were treated with further escalating doses of Leuvectin: 300 μg twice a week for 3 weeks, 750 μg weekly for 6 weeks, and 1,500 μg weekly for 6 weeks. RESULTS: There were no drug-related grade 4 toxicities and only one grade 3 toxicity, but the majority ofpatients experienced mild constitutional symptoms after treatment. In the phase I/II studies, 45 patients were assessable for response (14 with RCC, 16 with melanoma, and 15 with sarcoma). Two patients with RCC and one with melanoma have achieved partial responses lasting from 16 to 19 months and continuing. In addition, two RCC, three melanoma, and six sarcoma patients had stable disease lasting from 3 to 18 months and continuing. The plasmid was detected by polymerase chain reaction assay in the posttreatment samples of 29 of 46 evaluated patients. Immunohistochemistry studies on serial biopsy specimens showed increased IL-2 expression and CD8+ infiltration after treatment in the tumor samples of several patients (12 and 16, respectively). CONCLUSION: Direct intratumoral injection of Leuvectin is a safe and possibly effective immunotherapeutic approach in the treatment of certain tumor types.

Abstract Background Anti–tumor necrosis factor alpha ( TNF ‐α) agents are used to treat a variety of autoimmune and inflammatory conditions, including psoriasis. Paradoxically, numerous reports have documented new‐onset or exacerbation of psoriasis or psoriasiform skin lesions ( PSO ) in patients treated with these agents for conditions other than PSO—particularly in adults with inflammatory bowel disease ( IBD ). Not much is known regarding similar cases in children. Methods A retrospective chart review was performed on children younger than 19 years of age with IBD seen at the Mayo Clinic between 2003 and 2015 who developed new‐onset or recurrent PSO while undergoing anti‐ TNF ‐α therapy. Results Fourteen children developed PSO while undergoing anti‐ TNF ‐α therapy for IBD . All three anti‐ TNF ‐α agents (infliximab, adalimumab, certolizumab) used to treat IBD in this series led to induction or recurrence of PSO lesions. The median time to development of PSO was 11 months (range 0–48 mos), the median age was 15 years (range 12.5–17.5 yrs), and 57% of patients were male. IBD activity was quiescent in 93% of cases at PSO onset. Seven patients (50%) discontinued their initial anti‐ TNF ‐α therapy because of their skin disease. Ultimately, four patients (29%) had to discontinue all anti‐ TNF ‐α therapy to induce PSO resolution. Conclusion TNF ‐α antagonist–induced PSO in children with IBD is a rarely reported adverse reaction. PSO onset has a variable latency, but usually occurs during IBD remission, with a slight male bias. Nearly half of patients required a change in their initial anti‐ TNF ‐α agent despite conventional skin‐directed therapies, and one‐third of patients discontinued all anti‐ TNF ‐α therapy because of PSO .

PurposeTo investigate the ability of slip interface imaging (SII), a recently developed magnetic resonance elastography (MRE)‐based technique, to predict the degree of meningioma–brain adhesion, using findings at surgery as the reference standard.Materials and MethodsWith Institutional Review Board approval and written informed consent, 25 patients with meningiomas >2.5 cm in maximal diameter underwent preoperative SII assessment. Intracranial shear motions were introduced using a soft, pillow‐like head driver and the resulting displacement field was acquired with an MRE pulse sequence on 3T MR scanners. The displacement data were analyzed to determine tumor–brain adhesion by assessing intensities on shear line images and raw as well as normalized octahedral shear strain (OSS) values along the interface. The SII findings of shear line images, OSS, and normalized OSS were independently and blindly correlated with surgical findings of tumor adhesion by using the Cohen's κ coefficient and chi‐squared test.ResultsNeurosurgeons categorized the surgical plane as extrapial (no adhesion) in 15 patients, mixed in four, and subpial (adhesion) in six. Both shear line images and OSS agreed with the surgical findings in 18 (72%) cases (fair agreement, κ = 0.37, 95% confidence interval [CI]: 0.05–0.69), while normalized OSS was concordant with the surgical findings in 23 (92%) cases (good agreement, κ = 0.86, 95% CI: 0.67–1). The correlation between SII predictions (shear line images, OSS, and normalized OSS) and the surgical findings were statistically significant (chi‐squared test, P = 0.02, P = 0.02, and P < 0.0001, respectively).ConclusionSII preoperatively evaluates the degree of meningioma–brain adhesion noninvasively, allowing for improved prediction of surgical risk and tumor resectability.Level of Evidence: 1Technical Efficacy: Stage 1J. Magn. Reson. Imaging 2017;46:1007–1016.

Abstract Introduction Genetic loci for Alzheimer's disease (AD) have been identified in whites of European ancestry, but the genetic architecture of AD among other populations is less understood. Methods We conducted a transethnic genome‐wide association study (GWAS) for late‐onset AD in Stage 1 sample including whites of European Ancestry, African‐Americans, Japanese, and Israeli‐Arabs assembled by the Alzheimer's Disease Genetics Consortium. Suggestive results from Stage 1 from novel loci were followed up using summarized results in the International Genomics Alzheimer's Project GWAS dataset. Results Genome‐wide significant (GWS) associations in single‐nucleotide polymorphism (SNP)–based tests ( P < 5 × 10 −8 ) were identified for SNPs in PFDN1/HBEGF , USP6NL/ECHDC3 , and BZRAP1‐AS1 and for the interaction of the (apolipoprotein E) APOE ε4 allele with NFIC SNP. We also obtained GWS evidence ( P < 2.7 × 10 −6 ) for gene‐based association in the total sample with a novel locus, TPBG ( P = 1.8 × 10 −6 ). Discussion Our findings highlight the value of transethnic studies for identifying novel AD susceptibility loci.

Abstract As neurological surgery evolved into its own subspecialty early in the 20th century, a need arose to create an environment for communication and education among those surgeons working in this burgeoning surgical discipline. As the socioeconomic climate in health care began to change in the United States, an unforeseen need arose that was outside the scope of the American Association of Neurological Surgeons, Congress of Neurological Surgeons, and Society of Neurological Surgeons. The capacity to understand and address the evolving socioeconomic landscape and to offer a platform for advocacy required a new entity. Grassroots efforts of neurosurgeons at the state level ultimately yielded a formal organization of state neurosurgical societies to fill this void by recognizing, understanding, and addressing socioeconomic factors affecting the practice of neurological surgery. This formal organization became the Council of State Neurosurgical Societies (CSNS). The CSNS provides a forum in which state societies can meet to identify, understand, and advocate for policies on behalf of organized neurosurgery. The purpose of this paper is to detail the history of the formation of the CSNS. By understanding this history and the need for the development of the CSNS, it is hoped that its evolving role as a voice for neurological surgeons in the modern era of health care will be made clear.

PurposeThe purpose of this work is to derive and demonstrate constrained‐phase dual‐echo Dixon imaging within a maximum likelihood framework solved with a regularized graph‐cuts‐guided optimization.Theory and MethodsDual‐echo Dixon reconstruction is fundamentally underdetermined; however, adopting a constrained‐phase signal model reduces the number of unknowns and the nonlinear problem can be solved under a maximum likelihood framework. Period shifts in the field map (manifesting as fat/water signal swaps) must also be corrected. Here, a regularized cost function promotes a smooth field map and is solved with a graph‐cuts‐guided greedy binary optimization. The reconstruction shown here is compared to two other prevalent Dixon reconstructions in experimental phantom and human studies.ResultsReconstructed images of the water and fat signal are shown for a phantom study, and in vivo studies of foot/ankle, pelvis, and CE‐MRA of the thighs. The method shown here compared favorably with the other two methods. Large field inhomogeneities on the order of 20 ppm were resolved, thereby avoiding the fat and water signal swaps present in images reconstructed with the other methods.ConclusionConstrained‐phase dual‐echo Dixon imaging solved with a regularized graph‐cuts‐guided optimization has been derived and demonstrated to successfully separate water and fat images in the presence of large magnetic field inhomogeneities. Magn Reson Med 78:2203–2215, 2017. © 2017 International Society for Magnetic Resonance in Medicine.