Magnetic resonance imaging of oropharyngeal cancer

Magnetic resonance imaging (MRI) is a powerful tool for cross-sectional analysis of head and neck anatomy and pathology. This is especially true with regard to oropharyngeal neoplasms, where soft tissue spread, nodal disease, perineural extension, and osseous involvement may significantly alter therapy and prognosis. In this article, we will provide a background on oropharyngeal cancers and MRI techniques and strategies, describing potential advantages of MRI with regard to particular anatomic subsites of the oropharynx. Future imaging trends in perfusion and diffusion MRI of such cancers are also discussed.     

The current role of diagnostic imaging in the preoperative workup for refractory neonatal brachial plexus palsy

Introduction

Despite recent improvements in perinatal care, the incidence of neonatal brachial plexus palsy (NBPP) remains relatively common. CT myelography is currently considered to be the optimal imaging modality for evaluating nerve root integrity. Recent improvements in MRI techniques have made it an attractive alternative to evaluate nerve root avulsions (preganglionic injuries).

Aim

We demonstrate the utility of MRI for the evaluation of normal and avulsed spinal nerve roots. We also show the utility of ultrasound in providing useful preoperative evaluation of the postganglionic brachial plexus in patients with NBPP.

     

Left atrial thrombus despite continuous direct oral anticoagulant or warfarin therapy in patients with atrial fibrillation: insights into rates and timing of thrombus resolution

Purpose

Left atrial thrombus (LAT) may be detected by transesophageal echocardiography (TEE) in patients with atrial fibrillation (AF) or flutter (AFL) despite continuous anticoagulation therapy. We sought to examine the rates and timing of LAT resolution in response to changes in anticoagulation regimen.

Methods

A retrospective study of 1517 consecutive patients on ≥?4 weeks continuous oral anticoagulation (OAC) undergoing TEE prior to either direct current cardioversion or catheter ablation for AF or AFL was performed. Patients who had LAT on index TEE imaging and had follow-up TEEs were analyzed.

Results

Despite ≥?4 weeks of continuous anticoagulation therapy, 63 (4.2%) patients had LAT. Forty-four patients (median age 67 [IQR 58, 74]; 33 [75%] male; 25 [57%] on direct oral anticoagulant [DOAC]) had follow-up TEEs performed. Upon detection of LAT on index TEE, 8 patients switched from warfarin to a DOAC, 21 patients switched from a DOAC to warfarin or another DOAC, and 15 patients remained on the same OAC. Over median 4.2 months (IQR 2.9, 6.6), LAT resolution was seen in 25 (57%) patients. Of the 25 patients who had LAT resolution, 7 (28%) required TEE imaging >?6 months after index TEE to show clearance of thrombus. Rates of LAT resolution were similar between patients who had alterations in OAC and those who did not (52 vs. 60%; P?=?0.601).

Conclusions

After initial detection of left atrial thrombus despite uninterrupted anticoagulation for atrial fibrillation or flutter, >?40% patients have persistent clot despite additional extended anticoagulation.

     

Emergence of infections with Schistosoma mansoni in the Dhofar Governorate, Oman

Infections with Schistosoma mansoni were identified in an area of Dhofar (Oman), where this parasite had been virtually absent during recent years and was reported only very sporadically before 1992. In the present survey, performed late in 2001, between 1 and 13% of children (n=519) were found to excrete eggs (one Kato-Katz-smear) in four schools, from four different villages, but no infections were detected in additional five schools (n=281). Infections were light (<72 eggs/g of faeces) in 19 of the 36 children found infected. Serologic examination of sera (n=511) was done by ELISA (based on soluble worm antigen) and immunofluorescence tests (IFT, based on cryostat sections of adult S. mansoni). The prevalence according to serological tests was between 3 and 43% in the four schools with infected children. Positive test results were taken to reflect active infections, since false positive reactions could largely be excluded. According to ultrasound (US) examinations performed on 96 individuals (children and adults) from the four villages, livers were normal in all except three cases of mild pathology, which could be assigned to schistosomiasis mansoni (pattern C, ages 32-40 years). All data suggest that transmission of S. mansoni has been re-introduced only recently in Dhofar and that this emergence of schistosomiasis is limited to at most a few foci.     

TAK1 is a pivotal therapeutic target for tumor progression and bone destruction in myeloma

Along with tumor progression, the bone marrow microenvironment is skewed in multiple myeloma (MM), which underlies the unique pathophysiology of MM and confers aggressiveness and drug resistance in MM cells. TGF-b-activated kinase-1 (TAK1) mediates a wide range of intracellular signaling pathways. We demonstrate here that TAK1 is constitutively overexpressed and phosphorylated in MM cells, and that TAK1 inhibition suppresses the activation of NF-κB, p38MAPK, ERK and STAT3 in order to decrease the expression of critical mediators for MM growth and survival, including PIM2, MYC, Mcl- 1, IRF4, and Sp1, along with a substantial reduction in the angiogenic factor VEGF in MM cells. Intriguingly, TAK1 phosphorylation was also induced along with upregulation of vascular cell adhesion molecule-1 (VCAM-1) in bone marrow stromal cells (BMSC) in cocultures with MM cells, which facilitated MM cell-BMSC adhesion while inducing IL-6 production and receptor activator of nuclear factor κ-B ligand (RANKL) expression by BMSC. TAK1 inhibition effectively impaired MM cell adhesion to BMSC to disrupt the support of MM cell growth and survival by BMSC. Furthermore, TAK1 inhibition suppressed osteoclastogenesis enhanced by RANKL in cocultures of bone marrow cells with MM cells, and restored osteoblastic differentiation suppressed by MM cells or inhibitory factors for osteoblastogenesis overproduced in MM. Finally, treatment with the TAK1 inhibitor LLZ1640-2 markedly suppressed MM tumor growth and prevented bone destruction and loss in mouse MM models. Therefore, TAK1 inhibition may be a promising therapeutic option targeting not only MM cells but also the skewed bone marrow microenvironment in MM.     

ProPred analysis and experimental evaluation of promiscuous T-cell epitopes of three major secreted antigens of Mycobacterium tuberculosis

In the search for safe vaccine candidates against tuberculosis (TB), subunit vaccines including peptide-based candidates deserve consideration. However, an important requirement for such vaccine candidates is their promiscuous presentation to Th1 cells mediating protective immunity against TB, i.e. Th1 cells secreting IFN-gamma. The aim of the present study was to identify promiscuous Th1 cell epitopes of three major secreted antigens of Mycobacterium tuberculosis, i.e. ESAT-6, CFP10 and MPT70 by using a virtual matrix-based prediction program (ProPred) for peptide binding to 51 HLA-DR alleles. The ProPred analysis of these proteins was performed using the server (http:www.imtech.res.in/raghava/ProPed/). The peptides predicted to bind > 50% HLA-DR alleles included in the ProPred were considered promiscuous for binding predictions. Based on this criteria, one region in ESAT-6 (aa 69-77), two regions in CFP10 (aa 55-66 and aa 76-84) and four regions in MPT70 (aa 1-11, aa 81-95, aa 124-140 and aa 182-191) were considered promiscuous HLA-DR binders. The experimental evaluation of these regions, by using overlapping synthetic peptides for presentation to T-cells, confirmed the promiscuous nature of peptides covering the regions aa 69-77, aa 76-84 and aa 182-191 of ESAT-6, CFP10 and MPT70, respectively. These results demonstrate that the ProPred analysis can facilitate the selection of promiscuous peptides recognized by Th1 cells, and thus it can be useful in the identification of peptide-based vaccine candidates against TB.     

Revision Laparoscopic Gastric Bypass: An Effective Approach Following Failure of Primary Bariatric Procedures

Background  

The laparoscopic approach plays an important role in the primary surgical management of morbid obesity. This study evaluated the potential role of the laparoscopic approach to revision Roux-en-Y gastric bypass (LRYGB) in the management of selected patients who fail to lose adequate weight or regain weight after primary bariatric surgery.