A severe,late reaction to radiological contrast media mimicking a sepsis syndrome

An unusual, severe delayed reaction to non-ionic intravenous contrast media was observed. A 44-year-old man underwent a computed tomogaphy scan with non-ionic contrast media. Four hours later the patient collapsed with hypotension and cardiovascular shock. Aggressive management (including inotropic support and fluid resuscitation) was instituted in the intensive care unit. Rigorous imaging and biochemical and microbiological investigation failed to identify a source of this man’s circulatory collapse. A rapid recovery ensued and at 3 months follow-up the patient was suffering no residual effects from this event. To our knowledge, this is only the second report of a severe delayed reaction to radiological contrast media and the first that manifested as a prolonged hypotensive syndrome.     

Acute contrast reaction management by radiologists: A local audit study

Consultant radiologists and trainees must possess knowledge of optimal acute management of anaphylactic/anaphylactoid contrast reactions because patient survival depends upon prompt initial management. The aim of the present study is to assess the knowledge of first‐line management of these reactions among radiologists. Within one working day, and without prior knowledge, radiology consultants and trainees within four teaching hospitals in a major Australian capital city were asked to complete a confidential questionnaire regarding acute resuscitation management. Scenarios were presented of an adult who developed life‐threatening symptoms of anaphylaxis immediately after intravenous contrast administration, ventricular fibrillation and profound bradycardia. Questions were asked with regards to adrenaline, corticosteroid, antihistamines, intravenous volume expansion, cardio‐pulmonary rescuscitation and knowledge of the emergency telephone number. Sites were assessed for presence of an anaphylaxis management chart and also when each participant last completed a resuscitation course. Forty‐two participants were recruited. Overall, 53% of questions were answered correctly. Only 43% knew the adrenaline dose and if an incorrect dose was administered it was more likely to be an overdose. Notable inadequacies were also discovered with corticosteroid, atropine, antihistamine doses and intravenous fluid use. Only 26% had completed a resuscitation course in the past 2 years. Forty‐five percent knew the emergency telephone number and 55% of rooms using intravenous contrast contained an immediately visible chart for contrast reaction management. Radiologist and trainee knowledge of immediate life‐threatening contrast reaction management is deficient. Severe contrast reactions are uncommon with today's use of non‐ionic contrast, but they still occur. Experience in the management of anaphylaxis can only come from regular, compulsory training.     

The effects of X-ray contrast media on bacterial growth

Six widely used X-ray contrast media (XRC) were tested against nine commonly isolated organisms to determine the practicality of using XRC to outline body spaces prior to obtaining specimens for culture and to assess the feasibility of using XRC in divided doses to reduce cost. Preparations of Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Candida albicans, Streptococcus pyogenes and Streptococcus milleri in two approximate concentrations of 10⁴ and 10⁸ colony forming units/mL (cfu/mL) were inoculated into the following XRC: Conray 280, Hexabrix 320, lopamiro 370, Omnipaque 350, Ultravist 300 and Optiray 320 each in two concentrations. Sampling was performed in triplicate at 0, 2, 4 and 20 h with the 20 h counts made after exposure at both 22°C and 4°C. There were 16 significant interactions, predominantly with the Gram-negative organisms. Conray 280 produced the greatest number of effects. Most effects were bacteriostatic. Organisms were most susceptible at low concentration and after prolonged contact with XRC. No effect was seen with dilute XRC. All weekly sterility checks were negative. Non-ionic XRC have no significant effect on the growth of Gram-positive organisms and little effect on Gram-negative organisms if processing is performed promptly. Using standard aseptic technique, no contamination of XRC occurred, suggesting multi-dosing may be a safe and cost-effective method of XRC utilization.     

Renal toxicity of contrast agents in oncologic patients

Cancer patients frequently undergo imaging examinations to diagnosis but also to evaluate their responses to treatment. These patients are also at high risk of kidney impairment before considering the possible nephrotoxicity of their chemotherapy. In this context, it is overriding to know contrast agents induced risks and what are the good practices to avoid them. Renal function evaluation takes a major part in there. The X-ray radiology using iodinated contrast agent (ICA) exposes patients to acute renal failure. This induced nephropathy is prevented by adequate hydration prior to injection when the glomerular filtration rate (GFR) of the patient is less than 60 ml/min/1.73 m². For hardly nephrotoxic, gadolinium-based contrast agents (GBCA) injected in magnetic resonance imaging, were considered for a long as a safe alternative to ICA. Yet they may induce nephrogenic systemic fibrosis (NSF). The recommendations of European and U.S. drugs safety agencies have recently converged defining groups at risk of NSF based on the level of patients GFR and the type of GBCA used. How to assess the risk-benefit balance of the cancer patient for whom you should choose an informative, effective and safe imaging examination?     

胸部肿瘤三维适形放疗剂量造影剂影响的研究

目的:探讨CT造影剂对胸部肿瘤三维适形放疗剂量的影响.方法:共有40例患者入组,其中食管癌患者34例,肺癌患者6例,中位年龄62岁.在相同扫描条件下分别行CT平扫及增强扫描.在图像融合状态下,分别勾画大体靶区(GTV)、临床靶区(CTV)、计划靶区(PTV)以及危及器官,以平扫图像为基础图像进行剂量计算和计划优化,PTV边缘剂量1.8～2.0 Gy/次,总量45～66 Gy,并以此计划进行治疗.利用计划系统图像融合的功能,将在平扫图像(C-)上勾画的靶区及照射野设计复制到增强图像上,在增强图像(C+)上重新进行剂量计算;分别比较C+和C-图像中相对应的单次治疗照射野MU的不同(按照2 Gy/次计算),肿瘤中心点的剂量、肿瘤边缘点的CT值及剂量的不同;并进行统计学分析.结果:40例患者共有205个照射野,其平扫及增强图像射野MU分别为284.55±63.64和283.00±63.21,P=0.120;肿瘤中心点的剂量分别为平扫(45.219 5±9.561 4) Gy、增强(45.211 7±9.614 5)Gy,P=0.772;肿瘤边缘点的剂量分别为平扫(43.837 2±9.304 9)Gy、增强(42.904 5±9.164 5)Gy,P=0.001;边缘点的CT值分别为平扫(140.83±40.55) HU、增强(39.20±20.82) HU,P=0.00.结论:采用适当的扫描条件,对于胸部肿瘤,可以采用直接增强扫描的方式进行CT定位,使用CT增强扫描对放疗计划的优化影响不明显.     

Contrast media and the brain. The basis of computed tomography and magnetic resonance imaging enhancement: A review

The blood, cerebrospinal fluid (CSF), and extracellular fluid of the parenchyma form the fluid compartments of the brain with three interfaces between, namely the blood–brain interface (BBB), the CSF–brain interface, and the blood–CSF interface. When either water‐soluble iodinated contrast media (CM) or water‐soluble paramagnetic CM are injected intravenously, they are rapidly brought into contact with both the BBB and the blood–CSF interface. It is the behaviour of the water‐soluble CM at these two interfaces that determines the normal and abnormal enhancement patterns demonstrated by either CT or MRI. Unlike lipophilic solutes, current iodinated and MRI contrast media all have high affinities for plasma water, low affinities for plasma proteins and, in particular, extremely low partition coefficients. Therefore they do not penetrate the normal BBB. On the other hand, radiopharmaceuticals used in positron emission tomography (PET) and single photon emission computed tomography (SPECT) to demonstrate regional cerebral blood flow are highly lipophilic and readily cross the intact BBB completely during the first pass through the cerebral vasculature. It is the inability of the current iodinated and MRI contrast media to cross the normal intact BBB that is the basis of their use in CT and MRI studies of the brain.     

Functional imaging of the angiogenic switch in a transgenic mouse model of human breast cancer by dynamic contrast enhanced magnetic resonance imaging

Tumour progression depends on several sequential events that include the microenvironment remodelling processes and the switch to the angiogenic phenotype, leading to new blood vessels recruitment. Non‐invasive imaging techniques allow the monitoring of functional alterations in tumour vascularity and cellularity. The aim of this work was to detect functional changes in vascularisation and cellularity through Dynamic Contrast Enhanced (DCE) and Diffusion Weighted (DW) Magnetic Resonance Imaging (MRI) modalities during breast cancer initiation and progression of a transgenic mouse model (BALB‐neuT mice). Histological examination showed that BALB‐neuT mammary glands undergo a slow neoplastic progression from simple hyperplasia to invasive carcinoma, still preserving normal parts of mammary glands. DCE‐MRI results highlighted marked functional changes in terms of vessel permeability (K^trans, volume transfer constant) and vascularisation (v_p, vascular volume fraction) in BALB‐neuT hyperplastic mammary glands if compared to BALB/c ones. When breast tissue progressed from simple to atypical hyperplasia, a strong increase in DCE‐MRI biomarkers was observed in BALB‐neuT in comparison to BALB/c mice (K^trans = 5.3 ± 0.7E‐4 and 3.1 ± 0.5E‐4; v_p = 7.4 ± 0.8E‐2 and 4.7 ± 0.6E‐2 for BALB‐neuT and BALB/c, respectively) that remained constant during the successive steps of the neoplastic transformation. Consistent with DCE‐MRI observations, microvessel counting revealed a significant increase in tumour vessels. Our study showed that DCE‐MRI estimates can accurately detect the angiogenic switch at early step of breast cancer carcinogenesis. These results support the view that this imaging approach is an excellent tool to characterize microvasculature changes, despite only small portions of the mammary glands developed neoplastic lesions in a transgenic mouse model.     

A framework for the organization and delivery of systemic treatment

Background

Increasing systemic treatment and shortages of oncology professionals in Canada require innovative approaches to the safe and effective delivery of intravenous (IV) cancer treatment. We conducted a systematic review of the clinical and scientific literature, and an environmental scan of models in Canada, the United Kingdom, Australia, and New Zealand. We then developed a framework for the organization and delivery of IV systemic treatment.

Methods

The systematic review covered the medline, embase, cinahl, and HealthStar databases. The environmental scan retrieved published and unpublished sources, coupled with a free key word search using the Google search engine. The Systemic Treatment Working Group reviewed the evidence and developed a draft framework using evidence-based analysis, existing recommendations from various jurisdictions, and expert opinion based on experience and consensus. The draft was assessed by Ontario stakeholders and reviewed and approved by Cancer Care Ontario.

Results

The poor quantity and quality of the evidence necessitated a consensus-derived model. That model comprises four levels of care determined by a regional systemic treatment program and three integrated structures (integrated cancer programs, affiliate institutions, and satellite institutions), each with a defined scope of practice and a specific organizational framework.

Interpretation

New models of care are urgently required beyond large centres, particularly in geographically remote or rural areas. Despite limited applicable evidence, the development and successful implementation of this framework is intended to create sustainable, accessible, quality care and to measurably improve patient outcomes.     

Maternal smoking during pregnancy and the risk of childhood brain tumors: a meta-analysis of 6566 subjects from twelve epidemiological studies

Objective: Prior epidemiological studies suggest a possible association between maternal smoking during pregnancy and risk of childhood brain tumors. A meta-analysis was performed statistically pooling all available observational studies on this topic in order to evaluate this suspected association. Methods: Using previously described methods, a protocol was developed for a meta-analysis examining the association between maternal smoking during pregnancy and subsequent development of primary brain tumors in their offspring. Literature search techniques, study inclusion criteria and statistical procedures were prospectively defined. Data from epidemiological studies were pooled using a general variance-based meta-analytic method employing confidence intervals previously described by Greenland. The outcome of interest was a summary relative risk (RR_s) reflecting the risk of childhood brain tumor development associated with mother's smoking during the index pregnancy. Sensitivity analyses were performed when necessary to explain any observed statistical heterogeneity and/or to evaluate the impact of demographic or study characteristics on the summary estimate of effect. Results: Twelve observational studies meeting protocol specified inclusion criteria were obtained via a comprehensive literature search. These studies enrolled a total of 6566 patients. Analysis for homogeneity demonstrated that the data were homogeneous (P>0.50) and could be statistically combined. Pooling all twelve reports yielded an RR_s of 1.05 (0.90–1.21), a non-statistically significant result suggesting no clear association between maternal smoking during pregnancy and risk of childhood brain tumor development. Numerous sensitivity analyses examining the possible effect of study design and various patient characteristics failed to show any influence on the RR_s further supporting the observed lack of association. Conclusion: The available epidemiological data do not support a clear association between maternal smoking during pregnancy and pediatric brain tumor development. Although it appears likely that no association exists, limitations in study designs limit definitive conclusions based on available data.     

Prevalence of Aspergillus fumigatus and other fungal species in the sputum of adult patients with cystic fibrosis

Aspergillus fumigatus is often found in the respiratory tract secretions of patients with cystic fibrosis (CF), although the role of the fungus for progression of pulmonary disease remains unclear. This study aimed to investigate the frequency of A. fumigatus and other fungi in sputum of adult CF patients using different methods for culture and microscopy. Results from the analysis of 369 samples from 94 patients showed that A. fumigatus could be isolated in 45.7% of patients. Other moulds were rare, but the yeast Candida albicans was another frequent isolate, detected in 75.5% of patients. A comparison of different culture media showed no difference between a selective medium developed to specifically inhibit Pseudomonas aeruginosa and a standard fungal culture medium for growth of A. fumigatus, although both were more efficient for detection of fungi than other bacterial culture media. Fluorescent microscopy with calcofluor white was more sensitive for detection of fungal hyphae in undiluted sputum than standard methylene blue staining. This study shows that A. fumigatus and C. albicans have a high frequency in adult CF patients. Microbiological analysis should routinely include methods for specific identification of fungi to monitor for potential complications arising from fungal disease in these patients.     

中药红景天对肝组织中ALRmRNA的影响及可能的抗纤机制探讨

目的从分子水平探讨中药红景天抗肝纤维化的疗效及可能抗纤机制。方法Wistar大鼠90只雌雄各半,随机等分三组：空白组、模型组和红景天组。以CCL4造模,用中药红景天灌胃进行治疗干预。检测肝组织中ALR mRNA（肝再生增长因子mRNA）表达量及组织病理情况,组织切片采用HE染色和VG染色。结果ALR mRNA的表达增强,红景天组与对照组比较两者有显著性差异（P〈0.05）。肝组织病理学变化观察中药红景天组都在不同程度上缓解、逆转了肝纤维化的病变程度。结论中药红景天能显著通过促进ALR mRNA的表达可延缓或减轻肝硬化的发生。     

Comparison of intra‐arterial digital subtraction angiography using carbon dioxide by ‘home made’ delivery system and conventional iodinated contrast media in the evaluation of peripheral arterial occlusive disease of the lower limbs

To prospectively compare the feasibility, safety and diagnostic role of carbon dioxide (CO₂) digital subtraction angiography (DSA) using a ‘home made’ delivery system with iodinated contrast medium (ICM) DSA in the evaluation of peripheral arterial occlusive diseases (PAOD) of lower limbs. Twenty‐one patients (27 limbs; all men; mean age, 47.6 years) who presented with PAOD of lower limbs underwent DSA using both intra‐arterial CO₂ and ICM. Conventional ICM DSA was performed first and used as gold standard. Carbon dioxide was then injected by hand using a locally improvised home made plastic bag delivery system. Patient tolerance was assessed subjectively. Arteries from aortic bifurcation to the ankle were independently evaluated by two radiologists and graded for stenosis using a five‐point scale. For each patient, the quality of CO₂ DSA images were compared with the corresponding images of ICM DSA and an overall grade of ‘good’, ‘acceptable’ or ‘poor’ was assigned. Cohen’s kappa coefficient was used to determine inter‐observer agreement. Carbon dioxide opacified 86.2% (188/195) of major arteries and depicted stenosis adequately in 84.5% (191/226) of arterial segments. A good or acceptable image quality of CO₂ DSA was obtained in over 95% of patients. Infrapopliteal arteries were inadequately visualized. Mild pain was seen in six (28.6%) patients with both contrast agents; one patient developed severe pain during CO₂ DSA. Inter‐observer agreement was good (k > 0.75) at 70% of the segments. Administration of CO₂ into lower limb arteries is well tolerated. Carbon dioxide DSA using the locally improvised home made delivery system is a feasible and safe alternative to ICM DSA in the evaluation of PAOD. It provides adequate imaging of arteries of lower extremities except infrapopliteal segments.     

增强 T1- FLAIR 序列和磁化传递对比技术诊断脑微小转移瘤

目的：对比分析增强 T1液体衰减反转恢复（T1- FLAIR）序列和磁化传递对比（MTC）两种序列对脑内微小转移瘤的应用价值。方法：对60例患有脑转移瘤的病人行常规扫描后采用 T1- FLAIR 和 T1 WI ＋ MTC序列增强扫描,分别统计增强后 T1- FLAIR 和 T1 WI ＋ MTC 序列显示转移瘤的数目、大小、位置等,并比较二者对微小转移瘤的显示能力及2种序列图像的病灶-背景的对比度/噪声（C/ Ns）值。结果：60例脑转移瘤中,共计235个病灶,增强后 MTC 序列显示了231个病灶,显示率为98.3%,T1- FLAIR 序列显示了227个病灶,显示率为96.6%。T1 WI ＋ MTC 序列发现了 T1- FLAIR 序列不能显示的4个病灶,而 T1- FLAIR 序列证实了 T1 WI ＋ MTC 序列误判的2个病灶。T1 WI ＋ MTC 图像病灶-背景的 C/ Ns 值为29.85±6.43,T1- FLAIR图像病灶-背景的 C/ Ns 值为14.54±7.64,T1 WI ＋ MTC 序列的 C/ Ns 值高于 T1- FLAIR 序列的 C/ Ns 值（t=7.05,P ﹤0.05）。结论：增强 T1 WI ＋ MTC 序列和增强 T1- FLAIR 序列相互补充,二者结合能够最大程度满足微小转移瘤的显示和鉴别诊断的需要。     

乳腺癌99mTc-MIBI影像与P-糖蛋白表达的相关性

为了探讨活体乳腺恶性肿瘤对99mTc-甲氧基异丁基异腈(99mTc-MIBI)的摄取和肿瘤细胞P-糖蛋白(P-glyco-protein,P-gp)表达间的关系。2003年10月~2005年12月对40例未经治疗的乳腺癌患者进行99mTc-MIBI早期(10min)与延迟(120min)平面显像,计算其外排率(WOR)。显像后1周内进行手术治疗或化疗,术后应用免疫组化方法检测肿瘤标本P-gp表达,结果进行统计学计算。结果:WOR在P-gp阳性者为(12.8±8.2)%,高于P-gp阴性者(1.2±6.2)%,差异有统计学意义,t=3.42,P=0.01;WOR与肿瘤大小成正相关。初步研究结果显示,乳腺恶性肿瘤对99mTc-MIBI的摄取与P-gp表达呈明显负相关,即肿瘤细胞高度表达P-gp时,99mTc-MIBI摄取较低,99mTc-MIBI显像和肿瘤细胞P-gp表达相关性好,可成为体内无创检测肿瘤组织P-gp表达及耐药性的重要手段。     

Efficacy of Oral Cryotherapy in the Prevention of Oral Mucositis Associated with Cancer Chemotherapy: Systematic Review with Meta-Analysis and Trial Sequential Analysis

Background: This review aimed to evaluate the efficacy of oral cryotherapy in the prevention of chemotherapy-induced oral mucositis using meta-analysis and trial sequential analysis, as well as to assess the quality of the results by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Methods: A comprehensive search of three databases including Medline, Embase and Central was performed to identify randomized controlled trials that used oral cryotherapy for the prevention of chemotherapy-induced oral mucositis. The primary outcome was the incidence of oral mucositis for trials employing oral cryotherapy as the intervention for the prevention of oral mucositis. The meta-analysis was performed using the random-effects model and random errors of the meta-analyses were detected by trial sequential analysis. Results: A total of 14 RCTs with 1577 participants were included in the present meta-analysis. Patients treated with oral cryotherapy were associated with a significantly lower risk of developing oral mucositis of any grade (risk ratio (RR), 0.67 (95% CI: 0.56–0.81, p < 0.05)). Findings from the subgroup analyses showed that oral cryotherapy significantly reduced the risk of oral mucositis in patients undergoing bone marrow transplantation (RR 0.69, CI: 0.54–0.89, p < 0.05) as well as chemotherapy (RR 0.66, CI: 0.58–0.75, p < 0.05). Findings from the trial sequential analysis suggested that the evidence on oral cryotherapy as a preventive intervention for oral mucositis in patients with solid malignancies receiving conventional chemotherapy was conclusive. Conclusion: Oral cryotherapy is effective in preventing oral mucositis in patients undergoing chemotherapy for the management of solid malignancies. The use of oral cryotherapy in preventing oral mucositis in bone marrow transplantation settings showed promising efficacy, but the evidence is not conclusive and requires more high-quality randomized controlled trials.     

肿瘤坏死因子-α与异基因造血干细胞移植相关并发症

肿瘤坏死因子-α(TNF-α)是参与异基因造血干细胞移植(allo-HSCT)后相关并发症的关键细胞因子之一,近年来对其日益深入的研究显示,编码TNF-α的基因及微卫星的多态性与移植后移植物抗宿主病(GVHD)可能相关;TNF-α在移植后GVHD、特发性肺炎综合征(IPS)、巨细胞病毒(CMV)感染的发生发展过程中发挥了重要作用。为此,人们尝试针对TNF-α为靶点来治疗上述并发症,TNF-α的单克隆抗体依那西普(etanercept)、inflixi mab单药或联合免疫抑制剂等治疗移植相关并发症有着良好的耐受性,也取得了较好的疗效。     

Inhibition of muscle fibrosis results in increases in both utrophin levels and the number of revertant myofibers in Duchenne muscular dystrophy

Duchenne Muscular Dystrophy is characterized by: near absence of dystrophin in skeletal muscles; low percentage of revertant myofibers; up-regulation of utrophin synthesis; and a high degree of muscle fibrosis. In patient quadriceps femoris biopsies (n = 6, ages between 3–9 years) an inverse correlation was observed between the levels of collagen type I – representing fibrosis – and the levels of utrophin. This correlation was independent of the patient''s age and was observed in the entire muscle biopsy sections. In the mdx mice diaphragm (n = 6/group), inhibition of fibrosis by halofuginone resulted in increases in the levels of utrophin. The utrophin/fibrosis relationships were not limited to collagen type I, but also applied to other constituents of the fibrosis machinery. The inverse correlation was found also in old mdx mice with established fibrosis. In addition, inhibition of collagen type I levels was associated with increases in the numbers of revertant myofibers, both as single myofibers and in clusters in the diaphragm and the gastrocnemius.In summary, our results demonstrate an inverse correlation between the level of muscle fibrosis and the level of utrophin and that of the number of revertant myofibers. These findings may reveal common links between the fibrotic and utrophin-synthesis pathways and offer new insights into the regulation of utrophin synthesis.