Radiation dose reduction in pediatric great vessel stent computed tomography using iterative reconstruction: A phantom study

Background To study dose reduction using iterative reconstruction (IR) for pediatric great vessel stent computed tomography (CT). Methods Five different great vessel stents were separately placed in a gel-containing plastic holder within an anthropomorphic chest phantom. The stent lumen was filled with diluted contrast gel. CT acquisitions were performed at routine dose, 52% and 81% reduced dose and reconstructed with filtered back projection (FBP) and IR. Objective image quality in terms of noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) as well as subjective image quality were evaluated. Results Noise, SNR and CNR were improved with IR at routine and 52% reduced dose, compared to FBP at routine dose. The lowest dose level resulted in decreased objective image quality with both FBP and IR. Subjective image quality was excellent at all dose levels. Conclusion IR resulted in improved objective image quality at routine dose and 52% reduced dose, while objective image quality deteriorated at 81% reduced dose. Subjective image quality was not affected by dose reduction

Radiation dose reduction for CT assessment of urolithiasis using iterative reconstruction: A prospective intra-individual study

Objective: To assess the performance of hybrid (HIR) and model-based iterative reconstruction (MIR) in patients with urolithiasis at reduced-dose computed tomography (CT). Methods: Twenty patients scheduled for unenhanced abdominal CT for follow-up of urolithiasis were prospectively included. Routine dose acquisition was followed by three low-dose acquisitions at 40%, 60% and 80% reduced doses. All images were reconstructed with filtered back projection (FBP), HIR and MIR. Urolithiasis detection rates, gall bladder, appendix and rectosigmoid evaluation and overall subjective image quality were evaluated by two observers. Results: 74 stones were present in 17 patients. Half the stones were not detected on FBP at the lowest dose level, but this improved with MIR to a sensitivity of 100%. HIR resulted in a slight decrease in sensitivity at the lowest dose to 72%, but outperformed FBP. Evaluation of other structures with HIR at 40% and with MIR at 60% dose reductions was comparable to FBP at routine dose, but 80% dose reduction resulted in non-evaluable images. Conclusions: CT radiation dose for urolithiasis detection can be safely reduced by 40 (HIR)–60 (MIR) % without affecting assessment of urolithiasis, possible extra-urinary tract pathology or overall image quality. Key Points: • Iterative reconstruction can be used to substantially lower the radiation dose. • This allows for radiation reduction without affecting sensitivity of stone detection. • Possible extra-urinary tract pathology evaluation is feasible at 40–60% reduced dose

Neo-adjuvant chemotherapy followed by surgery versus surgery alone in high-risk patients with resectable colorectal liver metastases: The CHARISMA randomized multicenter clinical trial

Background: Efforts to improve the outcome of liver surgery by combining curative resection with chemotherapy have failed to demonstrate de

The mammalian gene function resource: The International Knockout Mouse Consortium

In 2007, the International Knockout Mouse Consortium (IKMC) made the ambitious promise to generate mutations in virtually every protein-coding gene of the mouse genome in a concerted worldwide action. Now, 5 years later, the IKMC members have developed highthroughput gene trapping and, in particular, gene-targeting pipelines and generated more than 17,400 mutant murine embryonic stem (ES) cell clones and more than 1,700 mutant mouse strains, most of them conditional. A common IKMC web portal (www.knockoutmouse.org) has been established, allowing easy access to this unparalleled biological resource. The IKMC materials considerably enhance functional gene annotation of the mammalian genome and will have a major impact on future biomedical research

Detection and localization of early- and late-stage cancers using platelet RNA

Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening

Colorectal liver metastases: Surgery versus thermal ablation (COLLISION) - a phase III single-blind prospective randomized controlled trial

Background: Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely accepted techniques to eliminate small unresectable colorectal liver metastases (CRLM). Although previous studies labelled thermal ablation inferior to surgical resection, the apparent selection bias when comparing patients with unresectable disease to surgical candidates, the superior safety profile, and the competitive overall survival results for the more recent reports mandate the setup of a randomized controlled trial. The objective of the COLLISION trial is to prove non-inferiority of thermal ablation compared to hepatic resection in patients with at least one resectable and ablatable CRLM and no extrahepatic disease. Methods: In this two-arm, single-blind multi-center phase-III clinical trial, six hundred and eighteen patients with at least one CRLM (≤3cm) will be included to undergo either surgical resection or thermal ablation of appointed target lesion(s) (≤3cm). Primary endpoint is OS (overall survival, intention-to-treat analysis). Main secondary endpoints are overall disease-free survival (DFS), time to progression (TTP), time to local progression (TTLP), primary and assisted technique efficacy (PTE, ATE), procedural morbidity and mortality, length of hospital stay, assessment of pain and quality of life (QoL), cost-effectiveness ratio (ICER) and quality-adjusted life years (QALY). Discussion: If thermal ablation proves to be non-inferior in treating lesions ≤3cm, a switch in treatment-method may lead to a reduction of the post-procedural morbidity and mortality, length of hospital stay and incremental costs without compromising oncological outcome for patients with CRLM. Trial registration:NCT03088150 , January 11th 2017

Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma

Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight

Anti-müllerian hormone as a marker of ovarian function in women after chemotherapy and radiotherapy for haematological malignancies

BACKGROUND: In female cancer survivors, the accelerated loss of primordial follicles as a result of gonadal damage may lead to premature ovarian failure (POF). However, the extent of the damage is unpredictable. Anti-Müllerian hormone (AMH) constitutes a sensitive marker of ovarian reserve. Serum AMH levels were measured to assess sub-clinical ovarian damage in patients treated with gonadotoxic therapy. METHODS: In 25 patients with haematological malignancies, serum AMH concentrations were measured prior to and after cancer therapy and were compared with normo-ovulatory controls. RESULTS: In all patients, AMH concentrations were lower than controls prior to treatment. Thirteen patients were treated with multi-drug chemotherapy. Although in most patients treated with chemotherapy menstrual cyclicity was restored, median serum AMH levels were lower than in controls. Twelve patients had stem cell transplantation (SCT) after total body irradiation. They all developed POF and their serum AMH concentrations were undetectable. CONCLUSIONS: Female cancer survivors treated with SCT all developed POF. Hence, in these patients fertility preservation should be considered. In patients treated with chemotherapy, ovarian reserve seems to be compromised as well

Clinical and histological determinants of smooth-muscle cell outgrowth in cultured atherectomy specimens: importance of thrombus organization

BACKGROUND: Coronary atherectomy provides a unique opportunity to obtain plaque tissue from a wide variety of clinical syndromes. We investigated the relation between the clinical status and histopathological substrate of tissue retrieved during directional coronary atherectomy and the proliferative and migratory potential of smooth-muscle cells judged from successful outgrowth during cell culture. METHOD