Multiple Intrahepatic Artery Aneurysms in a Patient with Behçet’s Disease: Use of Transcatheter Embolization for Rupture

Intrahepatic artery aneuryms are a rare and potentially life-threatening condition. We present the first case in the English literature of multiple intrahepatic artery aneuryms in a patient with Behçet’s disease who presented acutely with rupture. The ruptured aneurysm was treated successfully with transcatheter arterial coil embolization-CT and clinical follow-up confirming a good result. We discuss the management dilemma with regard to prophylactic embolization of the numerous other small asymptomatic intrahepatic aneurysms in this same patient.     

Arterial Compression during Overhead Throwing: A Risk for Arterial Injury?

Case studies reporting aneurysm formation in the axillary artery have been described in overhead throwing athletes, possibly due to repetitive arterial compression by the humeral head that has been transiently observed during sonographic diagnostic arm manoeuvres. Whether compression negatively alters arterial health has not been investigated and was the focus of this study. The throwing arm of elite overhead athletes was screened for inducible axillary artery compression. Compressors (COMP, n = 11, mean age: 20 (SD: 2) year, 7 male, 4 female) were age and sex matched with noncompressing (NONCOMP) athlete controls. Four indices of arterial health (flow mediated dilation [FMD], conduit artery vasodilatory capacity [CADC], glyceryl-trinitrate [GTN]-induced vasodilation and intima-media thickness [IMT]) were assessed with high-resolution ultrasound at the brachial and the axillary, artery. No significant between-group differences were observed at the brachial, or axillary, artery for FMD (brachial: COMP: mean (SD) 6.2 (3.1)%, NONCOMP: 6.1 (3.5)%, p = 0.967, axillary: COMP: 8.0 (5.5)%, NONCOMP: 9.0 (3.6)%, p = 0.602), CADC (brachial: COMP: 10.4 (3.4)%, NONCOMP: 10.4 (5.4)%, p = 0.999, axillary: COMP: 9.6 (4.2)%, NONCOMP: 8.5 (3.2)%, p = 0.492), GTN-induced vasodilation (brachial: COMP: 17.9 (5.1)%, NONCOMP:14.1 (7.2)%, p = 0.173, axillary: COMP: 9.5 (4.3)%, NONCOMP: 7.7 (3.1)%, p = 0.302) or IMT (brachial: p = 0.084, axillary: p = 0.581). These results suggest that transient arterial compression, observed during diagnostic arm manoeuvres in overhead throwing athletes, is not associated with abnormal indices of artery function or structure and that other mechanisms must be responsible for the published cases of aneurysm formation in elite athletes performing overhead throwing actions. (E-mail: c.stapleton@ljmu.ac.uk)     

NMDA-receptor activation and nitroxidative regulation of the glutamatergic pathway during nociceptive processing

The role of peroxynitrite (PN) as a mediator of nociceptive signaling is emerging. We recently reported that the development of central sensitization that follows the intraplantar injection of carrageenan in rats is associated with spinal PN synthesis. We now demonstrate that a significant pathway through which spinal PN modulates central sensitization is post-translational tyrosine nitration of key proteins involved in the glutamatergic pathway, namely glutamate transporter GLT-1 and glutamine synthetase (GS). We also reveal that spinal activation of the N-methyl-d-aspartate (NMDA) receptor provides a source of PN in this setting. Intraplantar injection of carrageenan led to the development of thermal hyperalgesia as well as nitration of GLT-1 and GS in dorsal horn tissues. Pretreatment with the PN decomposition catalyst FeTM-4-PyP⁵⁺ [Fe(III)5,10,15,20-tetrakis(N-methylpyridinium-4-yl)porphyrin] or the NMDA receptor antagonist MK-801 blocked the development of hyperalgesia. Carrageenan-induced hyperalgesia was also associated with nitration and inactivation of spinal mitochondrial superoxide dismutase (MnSOD) known to provide a critical source of PN during central sensitization. Nitration of GLT-1 and GS contributes to central sensitization by enhancing glutamatergic neurotransmission. Our results support the critical role of nitroxidative stress in the development of hyperalgesia and suggest that post-translational nitration of enzymes and transporters linked to glutamatergic neurotransmission represent a novel mechanism of central sensitization.     

The international diffuse intrinsic pontine glioma registry: an infrastructure to accelerate collaborative research for an orphan disease

Diffuse intrinsic pontine glioma (DIPG), a rare, often fatal childhood brain tumor, remains a major therapeutic challenge. In 2012, investigators, funded by the DIPG Collaborative (a philanthropic partnership among 29 private foundations), launched the International DIPG Registry (IDIPGR) to advance understanding of DIPG. Comprised of comprehensive deidentified but linked clinical, imaging, histopathological, and genomic repositories, the IDIPGR uses standardized case report forms for uniform data collection; serial imaging and histopathology are centrally reviewed by IDIPGR neuro-radiologists and neuro-pathologists, respectively. Tissue and genomic data, and cell cultures derived from autopsies coordinated by the IDIPGR are available to investigators for studies approved by the Scientific Advisory Committee. From April 2012 to December 2016, 670 patients diagnosed with DIPG have been enrolled from 55 participating institutions in the US, Canada, Australia and New Zealand. The radiology repository contains 3558 studies from 448 patients. The pathology repository contains tissue on 81 patients with another 98 samples available for submission. Fresh DIPG tissue from seven autopsies has been sent to investigators to develop primary cell cultures. The bioinformatics repository contains next-generation sequencing data on 66 tumors. Nine projects using data/tissue from the IDIPGR by 13 principle investigators from around the world are now underway. The IDIPGR, a successful alliance among philanthropic agencies and investigators, has developed and maintained a highly collaborative, hypothesis-driven research infrastructure for interdisciplinary and translational projects in DIPG to improve diagnosis, response assessment, treatment and outcome for patients.