Cross-reactivity among iodinated contrast agents: should we be concerned?

Background Although several papers deal with "cross-reactivity" in patients with iodinated contrast medium (ICM) hypersensitivity reactions (HSRs), there is no in-depth knowledge of this phenomenon. To define ICM-groups as potential reaction partners and to identify any potential clinical relevance in patients with ICM-HSRs. Methods The literature database PubMed was searched for eligible papers dealing with ICM-allergy and "cross-reactivity". The data presented by the papers was analyzed and individual patient data was extracted for re-evaluation based on a definition for both 'polyvalent reactivity' and 'cross-reactivity' as well as for chemical structure-dependent ICM-groups. Results Twenty-five original papers (with n=340 extracted patients) formed the study population. Incidences of polyvalent reactivity were non-significantly higher than incidences of cross-reactivity (both range from 0% to 100%). Crossover evaluation in reaction pairings (culprit ICM A with ICM B versus culprit ICM B with ICM A) showed concordance of only 30%. Data support rather non-cross-reactivity (individual reaction pattern) than cross-reactivity constellations. Conclusions The obtained results favour an individual reaction pattern, rather than a reactivity driven by chemical structures and so-called cross-reactivity

Assessment of the kidneys: magnetic resonance angiography, perfusion and diffusion

Renal magnetic resonance (MR) imaging has undergone major improvements in the past several years. This review focuses on the technical basics and clinical applications of MR angiography (MRA) with the goal of enabling readers to acquire high-resolution, high quality renal artery MRA. The current role of contrast agents and their safe use in patients with renal impairment is discussed. In addition, an overview of promising techniques on the horizon for renal MR is provided. The clinical value and specific applications of renal MR are critically discussed

Hepatic abscess caused by trans-gastric migration of a fishbone

Background Stomach or duodenal perforation due to foreign body are usually associated with the development of a walled-off abdominal mass or abscess, and are less prone to cause systemic signs of infection. Methods and Case presentation A 65-year-old man with no comorbidities was admitted for rapid onset of abdominal discomfort, fever, and chills. An abdominal computed tomography (CT) showed an 8 cm abscess in the left lobe of the liver. The lesion was aspirated under ultrasound guidance; cultures from the abscess grew Streptococcus constellatus. Chest CT scan, colonoscopy, esophagogastroduodenoscopy, and blood cultures were negative. The patient’s clinical status rapidly improved with antibiotic therapy, but a follow-up CT scan revealed the presence of a thin, 3 cm-long radiopaque object at the site of the previous abscess. A few months later, due to symptomatic cholelithiasis, the patient underwent elective laparoscopic cholecystectomy and concurrent removal of a 3 cm-long fishbone, which was embedded into the wall of the gastric antrum and the third segment of the liver, the latter which was partially resected. Results The small gastrotomy was reapproximated with a single resorbable stitch. The post-operative course was uneventful and at 6 month follow up, the patient was asymptomatic without evidence of residual abdominal pathology. Conclusions Asymptomatic perforation of the gastric wall by an ingested foreign body can occur and be subsequently complicated by a liver abscess. A contained perforation can be successfully managed conservatively

Radiation dose reduction: comparative assessment of publication volume between interventional and diagnostic radiology

PURPOSE:We aimed to quantify and compare awareness regarding radiation dose reduction within the interventional radiology and diagnostic radiology communities.METHODS:Abstracts accepted to the annual meetings of the Society of Interventional Radiology (SIR), the Cardiovascular and Interventional Radiological Society of Europe (CIRSE), the Radiological Society of North America (RSNA), and the European Congress of Radiology (ECR) between 2005 and 2015 were analyzed using the search terms “interventional/computed tomography” and “radiation dose/radiation dose reduction.” A PubMed query using the above-mentioned search terms for the years of 2005–2015 was performed.RESULTS:Between 2005 and 2015, a total of 14 520 abstracts (mean, 660±297 abstracts) and 80 614 abstracts (mean, 3664±1025 abstracts) were presented at interventional and diagnostic radiology meetings, respectively. Significantly fewer abstracts related to radiation dose were presented at the interventional radiology meetings compared with the diagnostic radiology meetings (162 abstracts [1% of total] vs. 2706 [3% of total]; P < 0.001). On average 15±7 interventional radiology abstracts (range, 6–27) and 246±105 diagnostic radiology abstracts (range, 112–389) pertaining to radiation dose were presented at each meeting. The PubMed query revealed an average of 124±39 publications (range, 79–187) and 1205±307 publications (range, 829–1672) related to interventional and diagnostic radiology dose reduction per year, respectively (P < 0.001).CONCLUSION:The observed increase in the number of abstracts regarding radiation dose reduction in the interventional radiology community over the past 10 years has not mirrored the increased volume seen within diagnostic radiology, suggesting that increased education and discussion about this topic may be warranted

Comparison of Dynamic and Liver-Specific Gadoxetic Acid Contrast-Enhanced MRI versus Apparent Diffusion Coefficients

Hepatic lesions often present diagnostic connundrums with conventional MR techniques. Hepatobiliary phase contrast-enhanced imaging with gadoxetic acid can aid in the characterization of such lesions. However, quantitative measures describing late-phase enhancement must be assessed relative to their accuracy of hepatic lesion classification.To compare quantitative parameters in gadoxetic acid contrast-enhanced dynamic and hepatobiliary phase imaging versus apparent diffusion coefficients in hepatic lesion characterization.57 patients with focal hepatic lesions on gadoxetic acid MR were included. Lesion enhancement at standard post-contrast time points and in the hepatobiliary phase (HB; 15 and 25 minutes post-contrast) was assessed via calculation of contrast (CR) and enhancement ratios (ER). Apparent diffusion coefficient (ADC) values were also obtained. Values for these parameters were compared among lesions and ROC analyses performed.HB enhancement was greatest with FNH and adenomas. HB ER parameters but not HB CR could distinguish HCC from benign entities (0.9 ER ROC AUC versus 0.5 CR ROC AUC). There was no statistically significant difference found between the 15 and 25 minutes HB time points in detection of any lesion (p>0.4). ADC values were statistically significantly higher with hemangiomas (p<0.05) without greater accuracy in lesion detection relative to HB phase parameters.Hepatobiliary phase gadoxetic acid contrast-enhanced MR characterizes focal hepatic lesions more accurately than ADC and conventional dynamic post-contrast time point enhancement parameters. ER values are generally superior to CR. No discernible benefit of 25 minute versus 15 minute delayed imaging is demonstrated

Repeatability and reproducibility of cerebral 23Na imaging in healthy subjects

Abstract Background Initial reports of 23Na magnetic resonance imaging (MRI) date back to the 1970s. However, methodological challenges of the technique hampered its widespread adoption for many years. Recent technical developments have overcome some of these limitations and have led to more optimal conditions for 23Na-MR imaging. In order to serve as a reliable tool for the assessment of clinical stroke or brain tumor patients, we investigated the repeatability and reproducibility of cerebral sodium (23Na) imaging in healthy subjects. Methods In this prospective, IRB approved study 12 consecutive healthy volunteers (8 female, age 31 ± 8.3) underwent three cerebral 23Na-MRI examinations at 3.0 T (TimTrio, Siemens Healthineers) distributed between two separate visits with an 8 day interval. For each scan a T1w MP-RAGE sequence for anatomical referencing and a 3D-density-adapted, radial GRE-sequence for 23Na-imaging were acquired using a dual-tuned (23Na/1H) head-coil. On 1 day, these scans were repeated consecutively; on the other day, the scans were performed once. 23Na-sequences were reconstructed according to the MP-RAGE sequence, allowing direct cross-referencing of ROIs. Circular ROIs were placed in predetermined anatomic regions: gray and white matter (GM, WM), head of the caudate nucleus (HCN), pons, and cerebellum. External 23Na-reference phantoms were used to calculate the tissue sodium content. Results Excellent correlation was found between repeated measurements on the same day (r2 = 0.94), as well as on a different day (r2 = 0.86). No significant differences were found based on laterality other than in the HCN (63.1 vs. 58.7 mmol/kg WW on the right (p = 0.01)). Pronounced inter-individual differences were identified in all anatomic regions. Moderate to good correlation (0.310 to 0.701) was found between the readers. Conclusion Our study has shown that intra-individual 23Na-concentrations in healthy subjects do not significantly differ after repeated scans on the same day and a pre-set time interval. This confirms the repeatability and reproducibility of cerebral 23Na-imaging. However, with manual ROI placement in predetermined anatomic landmarks, fluctuations in 23Na-concentrations can be observed

Genomic variation landscape of the human gut microbiome

While large-scale efforts have rapidly advanced the understanding and practical impact of human genomic variation, the latter is largely unexplored in the human microbiome. We therefore developed a framework for metagenomic variation analysis and applied it to 252 fecal metagenomes of 207 individuals from Europe and North America. Using 7.4 billion reads aligned to 101 reference species, we detected 10.3 million single nucleotide polymorphisms (SNPs), 107,991 short indels, and 1,051 structural variants. The average ratio of non-synonymous to synonymous polymorphism rates of 0.11 was more variable between gut microbial species than across human hosts. Subjects sampled at varying time intervals exhibited individuality and temporal stability of SNP variation patterns, despite considerable composition changes of their gut microbiota. This implies that individual-specific strains are not easily replaced and that an individual might have a unique metagenomic genotype, which may be exploitable for personalized diet or drug intake

Y-Chromosome Based Evidence for Pre-Neolithic Origin of the Genetically Homogeneous but Diverse Sardinian Population: Inference for Association Scans

The island of Sardinia shows a unique high incidence of several autoimmune diseases with multifactorial inheritance, particularly type 1 diabetes and multiple sclerosis. The prior knowledge of the genetic structure of this population is fundamental to establish the optimal design for association studies in these diseases. Previous work suggested that the Sardinians are a relatively homogenous population, but some reports were contradictory and data were largely based on variants subject to selection. For an unbiased assessment of genetic structure, we studied a combination of neutral Y-chromosome variants, 21 biallelic and 8 short tandem repeats (STRs) in 930 Sardinian males. We found a high degree of interindividual variation but a homogenous distribution of the detected variability in samples from three separate regions of the island. One haplogroup, I-M26, is rare or absent outside Sardinia and is very common (0.37 frequency) throughout the island, consistent with a founder effect. A Bayesian full likelihood analysis (BATWING) indicated that the time from the most recent common ancestor (TMRCA) of I-M26, was 21.0 (16.0–25.5) thousand years ago (KYA) and that the population began to expand 14.0 (7.8–22.0) KYA. These results suggest a largely pre-Neolithic settlement of the island with little subsequent gene flow from outside populations. Consequently, Sardinia is an especially attractive venue for case-control genome wide association scans in common multifactorial diseases. Concomitantly, the high degree of interindividual variation in the current population facilitates fine mapping efforts to pinpoint the aetiologic polymorphisms

Small molecules, big targets: drug discovery faces the protein-protein interaction challenge.

Protein-protein interactions (PPIs) are of pivotal importance in the regulation of biological systems and are consequently implicated in the development of disease states. Recent work has begun to show that, with the right tools, certain classes of PPI can yield to the efforts of medicinal chemists to develop inhibitors, and the first PPI inhibitors have reached clinical development. In this Review, we describe the research leading to these breakthroughs and highlight the existence of groups of structurally related PPIs within the PPI target class. For each of these groups, we use examples of successful discovery efforts to illustrate the research strategies that have proved most useful.JS, DES and ARB thank the Wellcome Trust for funding.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/nrd.2016.2

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease