Citations

Perianal fistulae in patients with Crohn’s disease (CD) can be associated with significant morbidity resulting in negative impact on quality of life. The last two decades have seen significant advancements in the management of perianal fistulas in CD, which has evolved into a multidisciplinary approach that includes gastroenterologists, colorectal surgeons, endoscopists and radiologists. Despite the introduction of new medical therapies such as antitumour necrosis factor and novel models of care delivery, the best fistula healing rates reported with combined medical and surgical approaches are approximately 50%. More recently, newer biologics, cell-based therapies as well as novel endoscopic and surgical techniques have been introduced raising new hopes that outcomes can be improved upon. In this review, we describe the modern management and the most recent advances in the management of complex perianal fistulising CD, which will likely impact clinical practice. We will explore optimal use of both older and newer biological agents, as well as new data on cell-based therapies. In addition, new techniques in endoscopic and surgical approaches will be discussed.

Purpose: To describe a modified up-and-over access technique for treatment of iliac artery aneurysms in patients with prior bifurcated stent-grafts for endovascular aneurysm repair (EVAR). Technique: This technique uses a coaxial 12-F flexible sheath that is docked with a through-and-through wire into a 7-F sheath advanced from the contralateral femoral approach. This maneuver allows both sheaths to be moved as a unit while maintaining position of the apex of the system as it loops over the flow divider, avoiding damage to or displacing the extant endograft. Once the 12-F sheath is positioned in the iliac limb of the aortic stent-graft and secured in place with the through-and-through wire, the repair is extended into the internal iliac artery using a bridging stent-graft or covered stent introduced via a coaxial sheath. Conclusion: The up-and-over technique with a flexible 12-F sheath mated with a 7-F sheath from the opposite side allows bilateral femoral access to be used for iliac branch device placement after prior aortic endograft procedures that create a higher, acutely angled bifurcation. Use of a through-and-through wire and a coaxial sheath for stent delivery creates a very stable platform for intervention.

Background: The prevalence of smoking among mental health and addiction (MHA) patients is 3 times higher than it is in the general population, yet this patient population has received little help to combat smoking. Considering this, psychosocial care centers (CAPS – Centros de Atenção Psicossocial) are strategic locations for integrating tobacco dependence treatment (TDT) into existing treatment activities. Methods: Our team provided an 8-hour training package to the staff of CAPS that have not been providing specialized TDT for smokers. Our curriculum included the following topics focused on the implementation of treatment for MHA smokers: management, epidemiology, medications, psychotherapy, and smoking/mental health assessment instruments. Results: Our team trained the staff of 17 CAPS units within 10 cities – which included more than 186 health professionals. There were many barriers encountered as we provided this training. A summary of problems we faced were as follows: resistance to incorporating TDT in addiction/mental health-care units, resistance to the implementation of cognitive-behavioral therapy (CBT) (psychodynamic therapy and harm reduction were preferred) and treatment for smoking is already implemented in primary care network; resistance to the use of medication in addiction treatment (a preference for psychotherapy and psychosocial approach). Conclusion: We learned a number of important lessons as we worked to improve the delivery of TDT to MHA patients in Brazil: provide clinicians an opportunity to explore how they feel/think about providing TDT to their clients at the very outset of the training, rather than focusing on a specific type of behavioral therapy for TDT (such as CBT), which some may find objectionable; use more generic descriptions of behavioral therapy such as ‘supportive counseling’; include training professionals who are open to other forms of behavioral therapy in addition to psychoanalysis and discuss the important impact that MHA units can have in improving the quality of life for their patients who smoke.

Abstract This American College of Radiology and American College of Nuclear Medicine joint clinical practice parameter is for performance of dopamine transporter single photon emission computed tomography (SPECT) imaging, for patients with movement disorders. Parkinsonian syndrome (PS) consists of a group of neurodegenerative diseases including Parkinson disease (PD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD), and dementia with Lewy bodies (DLB). Accurate diagnosis of PS is critical for clinical management. An important diagnostic dilemma is the differentiation of PS and non-neurodegenerative disorders, such as essential tremor (ET) or drug-induced tremor, due to the overlap of clinical symptoms. The management approach to these conditions is distinctly different. An abnormal iodine-123 ioflupane SPECT scan suggests a decreased amount of dopamine transporter in the striatum, that is, a diagnosis of nigrostriatal neurodegenerative PS, whereas a normal scan suggests ET or other nondegenerative parkinsonism (drug-induced, vascular, or psychogenic).

Abstract Genome Wide Association Studies (GWAS) are designed to identify single nucleotide polymorphisms (SNPs) mapping to genomic regions associated with a particular trait or disease. Currently, 19 genomic loci associated with risk for estrogen receptor negative breast cancer have been identified. However, for most of these loci the mechanisms driving susceptibility have remained elusive. The 2p23.2 locus, defined by SNP rs67073037 (p = 4.76 x 10-9), contains 79 SNPs exhibiting genome-wide significant associations as well as four candidate genes: SPDYA, TRMT61B, WDR43, and FAM179A. Post-GWAS functional analysis revealed two candidate causal regulatory elements: an enhancer-like element defined by SNP rs44017214 located in the first intron of the WDR43 gene; and a segment in the 3’-UTR region of WDR43 defined by SNPs rs11680458 and rs11331880 which are predicted to have allele specific binding of non-coding microRNAs miR-548 and miR-376, respectively. We validated allele specific transcription factor binding to rs44017214 using competitive binding of USF1/USF2 to the risk allele in both MCF10A and CAL51 cell lines in Electrophoretic Mobility Shift Assays (EMSA). Additionally, rs44017214 was removed using CRISPR-cas9, and expression of neighboring genes was evaluated by qRT-PCR. No change in expression was found for any gene in a 2 Mb region surrounding the SNP, with the exception of PLB1. This suggests that the enhancer element in the intron of WDR43 has PLB1 as its target. To assess the miRNA binding site impact on WDR43 expression the pMIR-REPORT Luciferase allele-specific vector was co-transfected with miR-141/200, miR548, or miR-376 in MCF10A cells. The rs1131880 allele C in the WDR43 3’-UTR lead to the suppression of luciferase expression by miR-376 compared to the G allele. This study reveals two independent regulatory mechanisms within the 2p23.2 locus; (i) modulation of enhancer activity by allele specific binding of transcription factors USF1/USF2 to rs4401714, and (ii) decreasing the expression of WDR43 through the formation of a miR-376 binding site at the 3’-UTR of the WDR43 gene. Elucidating the functional significance of these common variants in the novel susceptibility loci 2p23.2 furthers our knowledge of the etiology of estrogen receptor negative breast cancer. Citation Format: Carly M. Harro, Gustavo Mendoza-Fandino, Nicholas T. Woods, Xueli Li, Fergus J. Couch, Alvaro N. Monteiro. Two distinct regulatory mechanisms underlie estrogen receptor negative breast cancer susceptibility at the 2p23.2 locus [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1306. doi:10.1158/1538-7445.AM2017-1306