Diffusion-weighted MRI of abscess formations in children and young adults

Background

Diffusion-weighted MRI (DWI) is helpful for detection of brain abscess and pelvic abscess in adults. In the present study, we evaluated the diagnostic performance of DWI in children and young adults with abdominal and soft tissue abscess formations.

Methods

Seventeen patients (11 females, aged 13 ± 6 years) with suspected abdominal or soft-tissue abscess underwent routine MRI including free-breathing DWI and contrast-enhanced T1w imaging. Seventeen random age-matched patients with non-purulent abdominal fluid collections served as controls. Mean apparent diffusion coefficent (ADC) was measured for abscess, muscle, liver, spleen and kidney tissue as well as for cerebrospinal fluid, urine and free abdominal fluid.

Results

All fluid collections were identified on diffusion-weighted images. Thirteen of 14 confirmed abscess formations showed an ADC < 1.0 × 10^?3 mm²/s with a mean value of 0.80 ± 0.38 mm²/s. One tuberculous softtissue abscess had a higher ADC of 1.85 × 10^?3 mm²/s. Ring enhancement on T1w imaging was seen in three nonpurulent fluid collections. There were no false-positive findings in the control group.

Conclusions

Diffusion-weighted MRI is highly sensitive for abscess and may add specificity to contrast-enhanced T1w imaging of ring-enhancing fluid collections. DWI with free-breathing rapid image acquisition and without the need of intravenous contrast application constitutes a particularly useful choice in pediatric imaging.     

Influence of percutaneous mitral valve repair using the MitraClip® system on renal function in patients with severe mitral regurgitation

Background: In patients with mitral regurgitation (MR), changes in cardiac stroke volume, and thus renal preload and afterload may affect kidney function. Percutaneous mitral valve repair (PMVR) with the MitraClip® system can be a therapeutic alternative to surgical valve repair. The influence of MitraClip® therapy on renal function and clinical outcome parameters is unknown. Methods and Results: Sixty patients with severe MR underwent PMVR using the MitraClip® system in an open‐label observational study. Patients were stratified according to their renal function. All clips have been implanted successfully. Effective reduction of MR by 2–3 grades acutely improved KDOQI class. Lesser MR reduction (MR reduction of 0–1 grades) led to worsening of renal function in patients with pre‐existing normal or mild (KDOQI 1–2) compared to severe (KDOQI 3–4) renal dysfunction. Reduction of MR was associated with improvement in Minnesota Living with Heart Failure Questionnaire (MLHFQ), NYHA‐stadium, and 6‐minute walk test. Conclusion: Successful PMVR was associated with an improvement in renal function. The improvement in renal function was associated with the extent of MR reduction and pre‐existing kidney dysfunction. Our data emphasize the relevance of PVMR to stabilize the cardiorenal axis in patients with severe MR. © 2014 Wiley Periodicals, Inc.     

Comprehensive germline-genomic and clinical profiling in 160 unselected children and adolescents with cancer

In childhood cancer, the frequency of cancer-associated germline variants and their inheritance patterns are not thoroughly investigated. Moreover, the identification of children carrying a genetic predisposition by clinical means remains challenging. In this single-center study, we performed trio whole-exome sequencing and comprehensive clinical evaluation of a prospectively enrolled cohort of 160 children with cancer and their parents. We identified in 11/160 patients a pathogenic germline variant predisposing to cancer and a further eleven patients carried a prioritized VUS with a strong association to the cancerogenesis of the patient. Through clinical screening, 51 patients (31.3%) were identified as suspicious for an underlying cancer predisposition syndrome (CPS), but only in ten of those patients a pathogenic variant could be identified. In contrast, one patient with a classical CPS and ten patients with prioritized VUS were classified as unremarkable in the clinical work-up. Taken together, a monogenetic causative variant was detected in 13.8% of our patients using WES. Nevertheless, the still unclarified clinical suspicious cases emphasize the need to consider other genetic mechanisms including new target genes, structural variants, or polygenic interactions not previously associated with cancer predisposition.Subject terms: Oncogenesis, Paediatric cancer, Cancer genetics     

Cyclophosphamide and prednisone induction followed by cyclophosphamide mobilization effectively decreases the incidence of engraftment syndrome in patients with POEMS syndrome who undergo stem cell transplantation

High-dose chemotherapy with autologous stem cell transplantation (ASCT) can achieve excellent clinical responses in patients with POEMS syndrome (Jimenez Zepeda et al., Blood 2010;116:2403; Gertz et al., Am J Hematol 2005;79:319-328; Gherardi et al., Ann Neurol 1994;35:501-505; Gattinoni et al., Nat Rev Immunol 2006;6:383-393; Salem et al., J Immunol 2009;182:2030-2040; Salem et al., Cancer Immunol Immunother 2010;59:341-353; Salem et al., Cell Immunol 2010;261:134-143). However, High-dose melphalan with ASCT should be considered carefully due to its treatment-related morbidity (Vuckovic et al., Blood 2003;101:2314-2317), especially in patients with poor performance status owing to polyneuropathy and multiorgan involvement, such as cardiac, respiratory, and renal failure. Significant increases in the concentration of circulating macrophage colony-stimulating factor, erythropoietin, IL-6, and TNF-α, reach near maximal values at approximately day +12, predating neutrophil engraftment, and clinically manifest with fever, rash and edema (Dispenzieri et al., Eur J Haematol 2008;80:397-406). Depending on the definition used, approximately 50% of patients satisfied criteria for engraftment syndrome (ES) (Vuckovic et al., Blood 2003;101:2314-2317). ES occurs in 27-47% of patients who undergo ASCT; mortality rate is reported from 8% to 18% (Gattinoni et al., Nat Rev Immunol 2006;6:383-393; Vuckovic et al., Blood 2003;101:2314-2317). We have therefore reviewed our experience with ASCT in patients with POEMS syndrome who were treated with cyclophosphamide and prednisone as induction therapy followed by cyclophosphamide mobilization with an emphasis on treatment-related morbidity and frequency of ES. Our study confirms that ASCT is a feasible and efficacious treatment for patients with POEMS syndrome. In addition, the use of CP followed by cyclophosphamide mobilization decreases the incidence of PES leading to less morbidity and mortality rates.     

Promoter selection for the cytosine deaminase suicide gene constructs in gastric cancer

OBJECTIVE: Carcinomas of the digestive tract represent the second most abundant type of carcinomas in the Western world. During the past two decades, studies of genetic alterations in oncogenes, tumor-suppressor genes, and further cancer-related genes led to growing understanding of molecular mechanisms of gastrointestinal cancer resulting in a genetic progression model. Nevertheless, with a few exceptions, our knowledge of participating genes has not been exploited for gene therapy approaches. Therefore, we monitored promoter activity of a variety of genes shown to be significantly expressed in gastric tumor cells to select optimally active promoters for therapeutical recombinant DNA constructs. When driving a suicide gene these genetic elements can exert cytotoxic effects. METHODS: Using promoter-reporter gene (luciferase) constructs we compared the activities of KRT19, TFF1, SEL1L, MUC4, MUC1, CEL and hTERT by transfecting them into the gastrointestinal cell lines MKN45 and DAN-G for transient expression. After choosing strong promoters we tested the expression of the prokaryotic cytosine deaminase and its cytotoxic effect on the cell cultures. RESULTS: The promoters of SEL1L, MUC1 and KRT19 displayed the highest activity levels in reporter gene assays while other genes reported as upregulated in gastric cancer were moderately expressed. When driving cytosine deaminase in MKN45 cells, the SEL1L promoter induced a 66% cytotoxic effect and the TP1 promoter reached 82%. CONCLUSIONS: From a selection of nine promoter constructs three proved to upregulate the reporter gene well above the level of average activity. They also appear highly capable to drive a suicide gene construct, here tested using prokaryotic cytosine deaminase.     

Value of hematological indices versus VEGF as biomarkers of activity in Behçet’s disease

Clinical Rheumatology - The aim of this study is to investigate the value of several hematological indices, neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), red blood...