Tho2 is critical for the recruitment of Rrp6 to chromatin in response to perturbed mRNP biogenesis.

The eukaryotic THO complex coordinates the assembly of so-called messenger RNA-ribonucleoprotein particles (mRNPs), a process that involves cotranscriptional coating of nascent mRNAs with proteins. Once formed, mRNPs undergo a quality control step that marks them either for active transport to the cytoplasm, or Rrp6/RNA exosome-mediated degradation in the nucleus. However, the mechanism behind the quality control of nascent mRNPs is still unclear. We investigated the cotranscriptional quality control of mRNPs in budding yeast by expressing the bacterial Rho helicase, which globally perturbs yeast mRNP formation. We examined the genome-wide binding profiles of the THO complex subunits Tho2, Thp2, Hpr1, and Mft1 upon perturbation of the mRNP biogenesis, and found that Tho2 plays two roles. In addition to its function as a subunit of the THO complex, upon perturbation of mRNP biogenesis Tho2 targets Rrp6 to chromatin via its carboxy-terminal domain. Interestingly, other THO subunits are not enriched on chromatin upon perturbation of mRNP biogenesis and are not necessary for localizing Rrp6 at its target loci. Our study highlights the potential role of Tho2 in cotranscriptional mRNP quality control, which is independent of other THO subunits. Considering that both the THO complex and the RNA exosome are evolutionarily highly conserved, our findings are likely relevant for mRNP surveillance in mammals.

Regulation of the conserved 3'-5' exoribonuclease EXOSC10/Rrp6 during cell division, development and cancer.

The conserved 3'-5' exoribonuclease EXOSC10/Rrp6 processes and degrades RNA, regulates gene expression and participates in DNA double-strand break repair and control of telomere maintenance via degradation of the telomerase RNA component. EXOSC10/Rrp6 is part of the multimeric nuclear RNA exosome and interacts with numerous proteins. Previous clinical, genetic, biochemical and genomic studies revealed the protein's essential functions in cell division and differentiation, its RNA substrates and its relevance to autoimmune disorders and oncology. However, little is known about the regulatory mechanisms that control the transcription, translation and stability of EXOSC10/Rrp6 during cell growth, development and disease and how these mechanisms evolved from yeast to human. Herein, we provide an overview of the RNA- and protein expression profiles of EXOSC10/Rrp6 during cell division, development and nutritional stress, and we summarize interaction networks and post-translational modifications across species. Additionally, we discuss how known and predicted protein interactions and post-translational modifications influence the stability of EXOSC10/Rrp6. Finally, we explore the idea that different EXOSC10/Rrp6 alleles, which potentially alter cellular protein levels or affect protein function, might influence human development and disease progression. In this review we interpret information from the literature together with genomic data from knowledgebases to inspire future work on the regulation of this essential protein's stability in normal and malignant cells.

Yeast RNA exosome activity is necessary for maintaining cell wall stability through proper protein glycosylation.

Nuclear RNA exosome is the main 3'→5' RNA degradation and processing complex in eukaryotic cells and its dysregulation therefore impacts gene expression and viability. In this work we show that RNA exosome activity is necessary for maintaining cell wall stability in yeast Saccharomyces cerevisiae. While the essential RNA exosome catalytic subunit Dis3 provides exoribonuclease catalytic activity, the second catalytic subunit Rrp6 has a noncatalytic role in this process. RNA exosome cofactors Rrp47 and Air1/2 are also involved. RNA exosome mutants undergo osmoremedial cell lysis at high temperature or at physiological temperature upon treatment with cell wall stressors. Finally, we show that a defect in protein glycosylation is a major reason for cell wall instability of RNA exosome mutants. Genes encoding enzymes that act in the early steps of the protein glycosylation pathway are down-regulated at high temperature in cells lacking Rrp6 protein or Dis3 exoribonuclease activity and overexpression of the essential enzyme Psa1, that catalyzes synthesis of the mannosylation precursor, suppresses temperature sensitivity and aberrant morphology of these cells. Furthermore, this defect is connected to a temperature-dependent increase in accumulation of noncoding RNAs transcribed from loci of relevant glycosylation-related genes.

Deciphering the Dynamic Landscape of Transcription-Associated mRNP Quality Control Components Over the Whole Yeast Genome.

In eukaryotic cells, aberrant mRNPs with processing and packaging defects are targeted co-transcriptionally by a surveillance system that triggers their nuclear retention and ultimately the degradation of their mRNA component by the 3'-5' activity of the exosome-associated exonuclease Rrp6. This mRNP quality control process is stimulated by the NNS complex (Nrd1-Nab3-Sen1), which otherwise mediates termination, processing, and decay of ncRNAs. The process involves also the exosome co-activator TRAMP complex (Trf4-Air2-Mtr4). Here, we describe a genome-wide approach to visualize the dynamic movement and coordination of these quality control components over the yeast chromosomes upon perturbation of mRNP biogenesis. The method provides valuable information on how the surveillance system is precisely coordinated both physically and functionally with the transcription machinery to detect the faulty events during perturbation of mRNP biogenesis. The overview shows also that the gathering of the quality control components over affected mRNA genes takes place at the expense of their commitment to be recruited at ncRNA genomic features, provoking termination and processing defects of ncRNAs.

Protocol for efficient fluorescence 3' end-labeling of native noncoding RNA domains.

Noncoding RNAs (ncRNAs) comprise a class of versatile transcripts that are highly involved in the regulation of a wide range of biological processes. Functional long ncRNAs (> 200 nts in length) often adopt secondary structures that arise co-transcriptionally. To maintain the secondary structure elements as well as preparation homogeneity of such transcripts, native-like conditions should be maintained throughout the in vitro synthesis, purification and chemical tagging processes. In this optimized protocol, we describe a simple method for obtaining homogenous samples followed by chemically tagging the 3' termini of natively-purified structured ncRNA domains that are longer than 200 nts. This protocol replaces traditional hazardous radioactive labeling with fluorescence tagging, and eliminates laborious and time consuming RNA purification and concentration steps and replaces them with straightforward recovery of RNA through centrifugal filtration, preserving the homogeneity and mono-dispersion of the preparations. The protocol provides:•An integrative, simple and straightforward approach for synthesis, purification and labeling of structured ncRNAs whilst maintaining their secondary structure intact.•Replacing hazardous, laborious and time-consuming radioactive labeling of RNA with much simpler fluorescence tagging, thereby facilitating potential downstream applications such as electrophoretic mobility shift assay (EMSA).•A versatile protocol that could be applicable to a wide-range of chemical tags and in principle could be used to label DNA or RNA.

mRNA with Mammalian Codon Bias Accumulates in Yeast Mutants with Constitutive Stress Granules.

Stress granules and P bodies are cytoplasmic structures assembled in response to various stress factors and represent sites of temporary storage or decay of mRNAs. Depending on the source of stress, the formation of these structures may be driven by distinct mechanisms, but several stresses have been shown to stabilize mRNAs via inhibition of deadenylation. A recent study identified yeast gene deletion mutants with constitutive stress granules and elevated P bodies; however, the mechanisms which trigger its formation remain poorly understood. Here, we investigate the possibility of accumulating mRNA with mammalian codon bias, which we termed the model RNA, in these mutants. We found that the model RNA accumulates in dcp2 and xrn1 mutants and in four mutants with constitutive stress granules overlapping with P bodies. However, in eight other mutants with constitutive stress granules, the model RNA is downregulated, or its steady state levels vary. We further suggest that the accumulation of the model RNA is linked to its protection from the main mRNA surveillance path. However, there is no obvious targeting of the model RNA to stress granules or P bodies. Thus, accumulation of the model RNA and formation of constitutive stress granules occur independently and only some paths inducing formation of constitutive stress granules will stabilize mRNA as well.

Perturbation of mRNP biogenesis reveals a dynamic landscape of the Rrp6-dependent surveillance machinery trafficking along the yeast genome.

Eukaryotic cells have evolved a nuclear quality control (QC) system to monitor the co-transcriptional mRNA processing and packaging reactions that lead to the formation of export-competent ribonucleoprotein particles (mRNPs). Aberrant mRNPs that fail to pass the QC steps are retained in the nucleus and eliminated by the exonuclease activity of Rrp6. It is still unclear how the surveillance system is precisely coordinated both physically and functionally with the transcription machinery to detect the faulty events that may arise at each step of transcript elongation and mRNP formation. To dissect the QC mechanism, we previously implemented a powerful assay based on global perturbation of mRNP biogenesis in yeast by the bacterial Rho helicase. By monitoring model genes, we have shown that the QC process is coordinated by Nrd1, a component of the NNS complex (Nrd1-Nab3-Sen1) involved in termination, processing and decay of ncRNAs which is recruited by the CTD of RNAP II. Here, we have extended our investigations by analyzing the QC behaviour over the whole yeast genome. We performed high-throughput RNA sequencing (RNA-seq) to survey a large collection of mRNPs whose biogenesis is affected by Rho action and which can be rescued upon Rrp6 depletion. This genome-wide perspective was extended by generating high-resolution binding landscapes (ChIP-seq) of QC components along the yeast chromosomes before and after perturbation of mRNP biogenesis. Our results show that perturbation of mRNP biogenesis redistributes the QC components over the genome with a significant hijacking of Nrd1 and Nab3 from genomic loci producing ncRNAs to Rho-affected protein-coding genes, triggering termination and processing defects of ncRNAs.

Iterative reconstructions in multiphasic CT imaging of the liver: qualitative and task-based analyses of image quality.

AIM: To evaluate the clinical benefits on image quality (IQ) of adaptive statistical iterative reconstruction (ASIR) and model-based iterative reconstruction (MBIR) in multiphasic liver CT compared to filtered back-projection (FBP), in patients and on phantoms using a novel task-based metric. MATERIALS AND METHODS: Image data of 65 patients who underwent a routine multiphasic liver CT during a 1-month period were reconstructed with FBP, ASIR50, ASIR80, and MBIR. IQ was assessed qualitatively by ranking the most distal hepatic artery (HA) and portal vein (PV) visible; and quantitatively by measuring contrast-to-noise ratio (CNR) of the liver parenchyma, HA and PV. IQ was compared between each reconstruction and correlated to CNR and detectability index (d') measurements computed on phantoms scanned with the same CT protocol as for patients. RESULTS: HA and PV were seen more distally on MBIR and ASIR80 compared to FBP (p≤0.001). The CNR correlated weakly between patient and phantom (r=0.76 and 0.80 for HA and PV, respectively), whereas d' correlated strongly with the division order of HA and PV (r=0.96 and 0.95, respectively). CONCLUSION: MBIR and ASIR significantly improve the IQ of multiphasic liver CT, especially through better distal detection of HA and PV, in agreement with the adapted task-based metric d' estimated on phantoms.

Recombinant yeast and human cells as screening tools to search for antibacterial agents targeting the transcription termination factor Rho.

The alarming issue of antibiotic resistance expansion requires a continuous search for new and efficient antibacterial agents. Here we describe the design of new tools to screen for target-specific inhibitors of the bacterial Rho factor directly inside eukaryotic cells. Rho factor is a global regulator of gene expression which is essential to most bacteria, especially Gram-negative. Since Rho has no functional or structural homolog in eukaryotes, it constitutes a valuable and well known bacterial target as evidenced by its inhibition by the natural antibiotic, Bicyclomycin. Our screening tools are based on perturbation of mRNA processing and packaging reactions in the nucleus of eukaryotic cells by the RNA-dependent helicase/translocase activity of bacterial Rho factor leading to a growth defect phenotype. In this approach, any compound that impedes Rho activity should restore growth to yeast or human cells expressing Rho protein, providing valuable means to screen for target-specific antibacterial agents within the environment of a eukaryotic cell. The yeast tool expressing E. coli Rho factor was validated using Bicyclomycin as the control antibacterial agent. The validation of the screening tool was further extended with a stable human cell line expressing Rho factor conditionally. Finally, we show that Rho factors from different bacterial pathogens can also be designed as yeast-based screening tools which can reveal subtle variations in the functional features of the proteins.

Usefulness of T2 ratio in the diagnosis and prognosis of cardiac amyloidosis using cardiac MR imaging.

PURPOSE: To detect if a difference of T2 ratio, defined as the signal intensity (SI) of the myocardium divided by the SI of the skeletal muscle on T2-weigthed cardiac magnetic resonance (CMR) imaging, exists between patients with systemic amyloidosis, by comparison to control subjects. To determine if a relationship exists between T2 ratio and the overall mortality. MATERIALS AND METHODS: CMR imaging examinations of 73 consecutive patients (48 men, 25 women; mean age, 63 years±15[SD]) with amyloidosis and suspicion of CA and 27 control subjects were retrospectively analyzed after institutional review board approval. Final diagnosis of CA was retained in case of histological confirmation of CA, typical pattern of CA on imaging and/or positivity of 99Technetium-hydroxymethylene diphosphonate scintigraphy. Patients were divided in 2 groups according to the presence or the absence of CA. T2 ratios were calculated in patients with and those without CA and in control subjects with using analysis of variance. Prognostic value of T2 ratio was studied with a Kaplan-Meier curve. RESULTS: Thirty-five patients (51%) had CA and 33 (49%) were free from CA. T2 ratio was lower in patients with CA (1.18±0.29) than in patients without cardiac involvement (1.37±0.35) (P=0.03) and control subjects (1.45±0.24) (P=0.004). A T2 ratio of 1.36 was the best threshold value for predicting CA with a sensitivity of 63% and a specificity of 73%. Kaplan-Meier analysis showed a significant relationship between a shortened overall survival and a T2 ratio<1.36. CONCLUSION: Patients with CA exhibit lower T2 ratio on CMR imaging by comparison with patients free of CA and control subjects.

Light-tunable Fano resonance in metal-dielectric multilayer structures.

High-Q optical Fano resonances realized in a variety of plasmonic nanostructures and metamaterials are very much promising for the development of new potent photonic devices, such as optical sensors and switches. One of the key issues in the development is to establish ways to effectively modulate the Fano resonance by external perturbations. Dynamic tuning of the Fano resonance applying the mechanical stress and electric fields has already been demonstrated. Here, we demonstrate another way of tuning, i.e., photo-tuning of the Fano resonance. We use a simple metal-dielectric multilayer structure that exhibits a sharp Fano resonance originating from coupling between a surface plasmon polariton mode and a planar waveguide mode. Using a dielectric waveguide doped with azo dye molecules that undergo photoisomerization, we succeeded in shifting the Fano resonance thorough photo-modulation of the propagation constant of the waveguide mode. The present work demonstrates the feasibility of photo-tuning of the Fano resonance and opens a new avenue towards potential applications of the Fano resonance.

Co-transcriptional degradation by the 5'-3' exonuclease Rat1p mediates quality control of HXK1 mRNP biogenesis in S. cerevisiae.

The co-transcriptional biogenesis of export-competent messenger ribonucleoprotein particles (mRNPs) in yeast is under the surveillance of quality control (QC) steps. Aberrant mRNPs resulting from inappropriate or inefficient processing and packaging reactions are detected by the QC system and retained in the nucleus with ensuing elimination of their mRNA component by a mechanism that requires the catalytic activity of Rrp6p, a 3'-5' exonuclease associated with the RNA exosome. In previous studies, we implemented a new experimental approach in which the production of aberrant mRNPs is massively increased upon perturbation of mRNP biogenesis by the RNA-dependent helicase/translocase activity of the bacterial Rho factor expressed in S. cerevisiae. The analyses of a subset of transcripts such as PMA1 led us to substantiate the essential role of Rrp6p in the nuclear mRNP QC and to reveal a functional coordination of the process by Nrd1p. Here, we extended those results by showing that, in contrast to PMA1, Rho-induced aberrant HXK1 mRNPs are targeted for destruction by an Nrd1p- and Rrp6p-independent alternative QC pathway that relies on the 5'-3' exonuclease activity of Rat1p. We show that the degradation of aberrant HXK1 mRNPs by Rat1p occurs co-transcriptionally following decapping by Dcp2p and leads to premature transcription termination. We discuss the possibility that this alternative QC pathway might be linked to the well-known specific features of the HXK1 gene transcription such as its localization at the nuclear periphery and gene loop formation.

Ipsilateral breast cancer recurrence after Deep Inferior Epigastric Perforator (DIEP) flap reconstruction: Incidence and radiological presentation.

PURPOSE: To assess the incidence and presentation of ipsilateral cancer recurrences (ICR) after deep inferior epigastric perforator (DIEP) flap reconstruction for breast cancer. PATIENTS AND METHODS: Data of 247 consecutive women with DIEP flap reconstruction after breast cancer in our institution between 1997 and 2009 were retrospectively reviewed. RESULTS: Mean follow-up time was 4.1years±3.2 (SD) (median: 3years; range: 1month - 14years). Thirty-one patients (12.5%, 95%CI: =8.7-17.3) presented 34 relapses, in average 4.1years±2.6 after mastectomy: 14 (41%) were ipsilateral, 6 (18%) contralateral and 14 (41%) metastatic. ICRs occurred earlier (3.9 vs. 5.8years; P<0.05) than non-ICRs. Most ICRs (10/14, 71%) involved the periphery of the flap and presented as palpable nodules. The remaining (4/14, 29%) involved the axilla and 3/4 (75%) were palpable. Imaging procedures detected infra-clinical ICRs in 3 of 10 imaged patients (30%). CONCLUSION: ICRs after DIEP flap reconstruction are more frequent than contralateral recurrences suggesting the need for imaging follow-up of the reconstructed breast.

[Symptomatic extramedullary haematopoiesis in ß-thalassemia: A retrospective single centre study]. / Hématopoïèse extra-médullaire symptomatique au cours des ß-thalassémies: étude rétrospective monocentrique.

INTRODUCTION: Symptomatic extramedullary hematopoiesis (EH) is a rare but potentially severe phenomenon which occurs in ß-thalassemia. There are no treatment guidelines. METHODS: Retrospective single centre study including the cases of symptomatic EH encountered between 1997 and 2014 in a unit specialised in red blood cell genetic disorders. Description of clinical, biological and radiological characteristics of the patients, treatments received, and outcomes. RESULTS: Among 182 ß-thalassemia patients followed during the study period, 7 cases of symptomatic EH were diagnosed. They were 5 men and 2 women, and their mean age was 37 years. Four patients were splenectomised, two patients were regularly transfused, and four patients had already received erythropoietin. EH was localised in intravertebral areas and responsible for dorsal spinal cord compression in 5 patients, in paravertebral dorsal area in 1 patient, and in presacral area in 1 patient. The mean hemoglobin level at diagnosis was 7.9 g/dL. Treatment administered included: red cell transfusion in 6 cases, associated with hydroxyurea in 5 cases and/or radiotherapy in 3 patients. One patient was treated with surgery and HU. After a median follow-up of 41 months, clinical recovery was complete in 2 patients and partial in 5 patients. CONCLUSION: EH must be suspected in ß-thalassemia in patients presenting clinical signs of organ compression, and a typical radiological aspect. The functional prognosis depends on the rapidity of treatment, which includes red blood cell transfusion, hydroxyurea, radiotherapy, and rarely surgery. Long-term outcome is uncertain.

Ruptured visceral artery aneurysms.

Visceral artery aneurysms are rare but their estimated mortality due to rupture ranges between 25 and 70%. Treatment of visceral artery aneurysm rupture is usually managed by interventional radiology. Specific embolization techniques depend on the location, affected organ, locoregional arterial anatomy, and interventional radiologist skill. The success rate following treatment by interventional radiology is greater than 90%. The main complication is recanalization of the aneurysm, showing the importance of post-therapeutic monitoring, which should preferably be performed using MR imaging.

Breast tomosynthesis: Dosimetry and image quality assessment on phantom.

PURPOSE: To evaluate using phantom study the average glandular dose (AGD) and image quality in breast tomosynthesis. MATERIALS AND METHODS: The study was performed with a full-field digital mammography system (Mammomat Inspiration(®), Siemens, Erlangen, Germany) combined with tomosynthesis equipment (3D). For AGD evaluation, polymethyl methacrylate (PMMA) plates and a dosimeter were used to directly measure the absorbed doses in 2D and in 3D. The doses were then compared to the doses displayed on the equipment using the Mann-Whitney test. Three phantoms, accredited for 2D digital mammography (MTM 100, ACR RMI 156, BR3D), were imaged three times in 2D then in 3D. For each acquisition, the AGD was recorded. For image quality assessment, scores, defined by the rate of visible inserts, obtained for each acquisition both in 2D and in 3D, and for each phantom, were compared (Kruskall-Wallis and post-hoc Dunn tests). RESULTS: There was no significant difference between the measured and displayed AGD, both in 2D and in 3D imaging (P>0.05). With identical acquisition parameters, AGD were significantly greater in 3D than in 2D P<0.01). For phantoms MTM 100 and ACR RMI 156, there was no significant difference between the rate of visible inserts in 2D and in 3D (P=0.06 and P=0.36, respectively). However for phantom BR3D, the rate was significantly higher in 3D than in 2D (P<0.0001). CONCLUSION: Doses are significantly greater in 3D than in 2D. With tomosynthesis, out of the three phantoms tested, only phantom BR3D showed a higher rate of visible inserts.

In situ footprinting of E. coli transcription elongation complex with chloroacetaldehyde.

The structure and dynamics of Escherichia coli transcription elongation complex are now well documented. However, most of the studies have been conducted in vitro and frequently under artificial conditions that facilitate the biochemical characterization of the complex. Thus, little is known about relevance of these results for the regulatory aspects of transcription elongation inside the cell. Here, we describe the use of a single-strand-specific probe chloroacetaldehyde for in situ footprinting of E. coli elongation complex temporarily halted by a protein roadblock. The method provides valuable information on the dynamic features of transcriptionally engaged RNA polymerase within the cellular environment.

Double inversion recovery MR sequence for the detection of subacute subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The diagnosis of subacute subarachnoid hemorrhage is important because rebleeding may occur with subsequent life-threatening hemorrhage. Our aim was to determine the sensitivity of the 3D double inversion recovery sequence compared with CT, 2D and 3D FLAIR, 2D T2*, and 3D SWI sequences for the detection of subacute SAH. MATERIALS AND METHODS: This prospective study included 25 patients with a CT-proved acute SAH. Brain imaging was repeated between days 14 and 16 (mean, 14.75 days) after clinical onset and included MR imaging (2D and 3D FLAIR, 2D T2*, SWI, and 3D double inversion recovery) after CT (median delay, 3 hours; range, 2-5 hours). A control group of 20 healthy volunteers was used for comparison. MR images and CT scans were analyzed independently in a randomized order by 3 blinded readers. For each subject, the presence or absence of hemorrhage was assessed in 4 subarachnoid areas (basal cisterns, Sylvian fissures, interhemispheric fissure, and convexity) and in brain ventricles. The diagnosis of subacute SAH was defined by the presence of at least 1 subarachnoid area with hemorrhage. RESULTS: For the diagnosis of subacute SAH, the double inversion recovery sequence had a higher sensitivity compared with CT (P < .001), 2D FLAIR (P = .005), T2* (P = .02), SWI, and 3D FLAIR (P = .03) sequences. Hemorrhage was present for all patients in the interhemispheric fissure on double inversion recovery images, while no signal abnormality was noted in healthy volunteers. Interobserver agreement was excellent with double inversion recovery. CONCLUSIONS: Our study showed that the double inversion recovery sequence has a higher sensitivity for the detection of subacute SAH than CT, 2D or 3D FLAIR, 2D T2*, and SWI.

[Necrotizing fasciitis: results of a survey on management practices in French-speaking intensive care units]. / Prise en charge des dermohypodermites bactériennes nécrosantes et fasciites nécrosantes en réanimation : résultats d'une enquête de pratique francophone.

OBJECTIVES: Necrotizing fasciitis (NF) are rare and severe soft tissue infections associated with a high mortality rate. In order to assess the management of NF in French-speaking intensive care units (ICUs), we conducted a survey endorsed by the French Society of Anesthesia and Intensive Care (SFAR). STUDY DESIGN: Online self-administered survey. METHODS: A link to an online survey was sent by email to 4620 anesthesiologists and/or intensivists and was available online from January to February 2014. RESULTS: One hundred and seventy-five physicians (3.8%) who worked in 135 ICUs filled out the online survey. Among respondents, 42% reported having managed up to two patients with NF during the previous year; 59% and 72% of respondents reported not having a surgical and a medical specialist consultant, respectively. A delayed access to the operating room (OR) of more than 6hours was reported in 31% of cases and access to the OR was reported not to be routinely considered as a priority in 13% of cases. Only 17% of respondents reported that time to transfer to the OR was never a cause for delayed surgery. The main causes for delayed surgery were: delayed diagnosis (45%), delayed validation of surgical intervention (37%), and difficulty of access to the OR (8%). Finally, 83% of respondents estimated that creating dedicated multidisciplinary teams for managing NFs could lead to improving outcomes. CONCLUSION: This survey illustrates the heterogeneous management of NF in French-speaking ICUs and points out several logistical aspects that should be improved to reduce the time to the first surgical debridement.

Imaging strategies before beginning treatment of colorectal liver metastases.

The management of colorectal intrahepatic metastases before resection is multidisciplinary and radiologists and nuclear medicine specialists play a major role. In accordance with the French National Guide for appropriate use of diagnostic imaging, the approach should be multimodal: a chest-abdomen and pelvic (CAP) CT scan and hepatic MRI are mandatory while PET-CT provides important additional information, in particular on intra-abdominal extrahepatic metastases. This multimodal approach emphasizes the importance of early and appropriate use of imaging in these patients, as well as the central role of multidisciplinary meetings in oncology.