The host inflammatory response contributes to disease severity in Crimean-Congo hemorrhagic fever virus infected mice.

Crimean-Congo hemorrhagic fever virus (CCHFV) is an important human pathogen. In cell culture, CCHFV is sensed by the cytoplasmic RNA sensor retinoic acid-inducible gene I (RIG-I) molecule and its adaptor molecule mitochondrial antiviral signaling (MAVS) protein. MAVS initiates both type I interferon (IFN-I) and proinflammatory responses. Here, we studied the role MAVS plays in CCHFV infection in mice in both the presence and absence of IFN-I activity. MAVS-deficient mice were not susceptible to CCHFV infection when IFN-I signaling was active and showed no signs of disease. When IFN-I signaling was blocked by antibody, MAVS-deficient mice lost significant weight, but were uniformly protected from lethal disease, whereas all control mice succumbed to infection. Cytokine activity in the infected MAVS-deficient mice was markedly blunted. Subsequent investigation revealed that CCHFV infected mice lacking TNF-α receptor signaling (TNFA-R-deficient), but not IL-6 or IL-1 activity, had more limited liver injury and were largely protected from lethal outcomes. Treatment of mice with an anti-TNF-α neutralizing antibody also conferred partial protection in a post-virus exposure setting. Additionally, we found that a disease causing, but non-lethal strain of CCHFV produced more blunted inflammatory cytokine responses compared to a lethal strain in mice. Our work reveals that MAVS activation and cytokine production both contribute to CCHFV pathogenesis, potentially identifying new therapeutic targets to treat this disease.

Protein Kinase C subtype δ interacts with Venezuelan equine encephalitis virus capsid protein and regulates viral RNA binding through modulation of capsid phosphorylation.

Protein phosphorylation plays an important role during the life cycle of many viruses. Venezuelan equine encephalitis virus (VEEV) capsid protein has recently been shown to be phosphorylated at four residues. Here those studies are extended to determine the kinase responsible for phosphorylation and the importance of capsid phosphorylation during the viral life cycle. Phosphorylation site prediction software suggests that Protein Kinase C (PKC) is responsible for phosphorylation of VEEV capsid. VEEV capsid co-immunoprecipitated with PKCδ, but not other PKC isoforms and siRNA knockdown of PKCδ caused a decrease in viral replication. Furthermore, knockdown of PKCδ by siRNA decreased capsid phosphorylation. A virus with capsid phosphorylation sites mutated to alanine (VEEV CPD) displayed a lower genomic copy to pfu ratio than the parental virus; suggesting more efficient viral assembly and more infectious particles being released. RNA:capsid binding was significantly increased in the mutant virus, confirming these results. Finally, VEEV CPD is attenuated in a mouse model of infection, with mice showing increased survival and decreased clinical signs as compared to mice infected with the parental virus. Collectively our data support a model in which PKCδ mediated capsid phosphorylation regulates viral RNA binding and assembly, significantly impacting viral pathogenesis.

Making computed tomography safer for patients with Crohn's disease.

Background and aims: Computed tomography (CT), often more accessible than magnetic resonance imaging (MRI), remains widely used though radiation exposure is an obvious disadvantage. We previously showed that modern CT technology can achieve over 70% reduction in radiation-dose without loss of accuracy. Here, we compare low- versus conventional-dose CT in patients with known Crohn's disease to assess clinical confidence and accuracy of the low-dose procedure in the semi-acute setting.Methods: A comparative study of low-dose CT with full iterative reconstruction (IR) versus conventional-dose CT was conducted in 50 consecutive outpatients with Crohn's disease. Clinicians were provided with the low-dose images and reports, whereas conventional-dose images were reviewed after 4 weeks.Results: The clinical question was adequately addressed with low-dose IR imaging in all cases. Complications of Crohn's were detected in 37/50 (74%) with no disagreement between low- and conventional-dose imaging. The effective radiation dose reduction was 76.5% (low-dose mean 2.15 mSv versus conventional-dose CT 6.99 mSv).Conclusion: Low-dose IR CT is safe and accurate for evaluating distribution and complications of known Crohn's disease in the outpatient setting. We propose that low-dose radiation imaging should be adopted as standard-of-care for the evaluation of Crohn's disease and an acceptable alternative to MR particularly in the acute setting. ClinicalTrials.gov: NCT03140306.

Computed tomography in cystic fibrosis lung disease: a focus on radiation exposure.

Thoracic computed tomography (CT) is the imaging reference method in the diagnosis, assessment and management of lung disease. In the setting of cystic fibrosis (CF), CT demonstrates increased sensitivity compared with pulmonary function tests and chest radiography, and findings correlate with clinical outcomes. Better understanding of the aetiology of CF lung disease indicates that even asymptomatic infants with CF can have irreversible pulmonary pathology. Surveillance and early diagnosis of lung disease in CF are important to preserve lung parenchyma and to optimise long-term outcomes. CF is associated with increased cumulative radiation exposure due to the requirement for repeated imaging from a young age. Radiation dose optimisation, important for the safe use of CT in children with CF, is best achieved in a team environment where paediatric radiologists work closely with paediatric respiratory physicians, physicists and radiography technicians to achieve the best patient outcomes. Despite the radiation doses incurred, CT remains a vital imaging tool in children with CF. Radiologists with special interests in CT dose optimisation and respiratory disease are key to the appropriate use of CT in paediatric imaging. Paediatric radiologists strive to minimise radiation dose to children whilst providing the best possible assessment of lung disease.

Protein Phosphatase 1α Interacts with Venezuelan Equine Encephalitis Virus Capsid Protein and Regulates Viral Replication through Modulation of Capsid Phosphorylation.

Protein phosphatase 1 (PP1) is a serine/threonine phosphatase which has been implicated in the regulation of a number of viruses, including HIV-1, Ebolavirus, and Rift Valley fever virus. Catalytic subunits of PP1 (PP1α, PP1ß, and PP1γ) interact with a host of regulatory subunits and target a wide variety of cellular substrates through a combination of short binding motifs, including an RVxF motif present in the majority of PP1 regulatory subunits. Targeting the RVxF-interacting site on PP1 with the small molecule 1E7-03 inhibits HIV-1, Ebolavirus, and Rift Valley fever virus replication. In this study, we determined the effect of PP1 on Venezuelan equine encephalitis virus (VEEV) replication. Treatment of VEEV-infected cells with 1E7-03 decreased viral replication by more than 2 logs (50% effective concentration [EC50] = 0.6 µM). 1E7-03 treatment reduced viral titers starting at 8 h postinfection. Viral replication was also decreased after treatment with PP1α-targeting small interfering RNA (siRNA). Confocal microscopy demonstrated that PP1α shuttles toward the cytosol during infection with VEEV and that PP1α colocalizes with VEEV capsid. Coimmunoprecipitation experiments confirmed VEEV capsid interaction with PP1α. Furthermore, immunoprecipitation and mass spectrometry data showed that VEEV capsid is phosphorylated and that phosphorylation is moderated by PP1α. Finally, less viral RNA is associated with capsid after treatment with 1E7-03. Coupled with data showing that 1E7-03 inhibits several alphaviruses, this study indicates that inhibition of the PP1α RVxF binding pocket is a promising therapeutic target and provides novel evidence that PP1α modulation of VEEV capsid phosphorylation influences viral replication.IMPORTANCE Venezuelan equine encephalitis virus (VEEV) causes moderate flu-like symptoms and can lead to severe encephalitic disease and potentially death. There are currently no FDA-approved therapeutics or vaccines for human use, and understanding the molecular underpinning of host-virus interactions can aid in the rational design of intervention strategies. The significance of our research is in identifying the interaction between protein phosphatase 1 (PP1) and the viral capsid protein. This interaction is important for viral replication, as inhibition of PP1 results in decrease viral replication. Inhibition of PP1 also inhibited multiple biomedically important alphaviruses, indicating that PP1 may be a potential therapeutic target for alphavirus-induced disease.

Low-dose CT imaging of the acute abdomen using model-based iterative reconstruction: a prospective study.

OBJECTIVES: Performance of a modified abdominopelvic CT protocol reconstructed using full iterative reconstruction (IR) was assessed for imaging patients presenting with acute abdominal symptoms. MATERIALS AND METHODS: Fifty-seven patients (17 male, 40 female; mean age of 56.5 ± 8 years) were prospectively studied. Low-dose (LD) and conventional-dose (CD) CTs were contemporaneously acquired between November 2015 and March 2016. The LD and CD protocols imparted radiation exposures approximating 10-20% and 80-90% those of routine abdominopelvic CT, respectively. The LD images were reconstructed with model-based iterative reconstruction (MBIR), and CD images with hybrid IR (40% adaptive statistical iterative reconstruction (ASIR)). Image quality was assessed quantitatively and qualitatively. Independent clinical interpretations were performed with a 6-week delay between reviews. RESULTS: A 74.7% mean radiation dose reduction was achieved: LD effective dose (ED) 2.38 ± 1.78 mSv (size-specific dose estimate (SSDE) 3.77 ± 1.97 mGy); CD ED 7.04 ± 4.89 mSv (SSDE 10.74 ± 5.5 mGy). LD-MBIR images had significantly lower objective and subjective image noise compared with CD-ASIR (p < 0.0001). Noise reduction for LD-MBIR studies was greater for patients with BMI < 25 kg/m2 than those with BMI ≥ 25 kg/m2 (5.36 ± 3.2 Hounsfield units (HU) vs. 4.05 ± 3.1 HU, p < 0.0001). CD-ASIR studies had significantly better contrast resolution, and diagnostic acceptability (p < 0.0001 for all). LD-MBIR studies had significantly lower streak artifact (p < 0.0001). There was no difference in sensitivity for primary findings between the low-dose and conventional protocols with the exception of one case of enteritis. CONCLUSIONS: Low-dose abdominopelvic CT performed with MBIR is a feasible radiation dose reduction strategy for imaging patients presenting with acute abdominal pain.

Comparison of transcriptional responses between pathogenic and nonpathogenic hantavirus infections in Syrian hamsters using NanoString.

BACKGROUND: Syrian hamsters infected with Andes virus (ANDV) develop a disease that recapitulates many of the salient features of human hantavirus pulmonary syndrome (HPS), including lethality. Infection of hamsters with Hantaan virus (HTNV) results in an asymptomatic, disseminated infection. In order to explore this dichotomy, we examined the transcriptome of ANDV- and HTNV-infected hamsters. RESULTS: Using NanoString technology, we examined kinetic transcriptional responses in whole blood collected from ANDV- and HTNV-infected hamsters. Of the 770 genes analyzed, key differences were noted in the kinetics of type I interferon sensing and signaling responses, complement activation, and apoptosis pathways between ANDV- and HTNV-infected hamsters. CONCLUSIONS: Delayed activation of type I interferon responses in ANDV-infected hamsters represents a potential mechanism that ANDV uses to subvert host immune responses and enhance disease. This is the first genome-wide analysis of hantavirus-infected hamsters and provides insight into potential avenues for therapeutics to hantavirus disease.

Use of Nanotrap particles for the capture and enrichment of Zika, chikungunya and dengue viruses in urine.

Nanotrap® (NT) particles are hydrogel microspheres developed for target analyte separation and discovery applications. NT particles consist of cross-linked N-isopropylacrylamide (NIPAm) copolymers that are functionalized with a variety of chemical affinity baits to enable broad-spectrum collection and retention of target proteins, nucleic acids, and pathogens. NT particles have been previously shown to capture and enrich arboviruses including Rift Valley fever and Venezuelan equine encephalitis viruses. Yet, there is still a need to enhance the detection ability for other re-emerging viruses such as Zika (ZIKV), chikungunya (CHIKV), and dengue (DENV) viruses. In this study, we exploited NT particles with different affinity baits, including cibacron blue, acrylic acid, and reactive red 120, to evaluate their capturing and enrichment capability for ZIKV, DENV and CHIKV in human fluids. Our results demonstrate that CN1030, a NT particle conjugated with reactive red 120, can recover between 8-16-fold greater genomic copies of ZIKV, CHIKV and DENV in virus spiked urine samples via RT-qPCR, superior to the other chemical baits. Also, we observed that CN1030 simultaneously enriched ZIKV, CHIKV and DENV in co-infection-based settings and could stabilize ZIKV, but not CHIKV infectivity in saliva spiked samples. CN1030 enriched viral detection at various viral concentrations, with significant enhancement observed at viral titers as low as 100 PFU/mL for ZIKV and 10 PFU/mL for CHIKV. The detection of ZIKV was further enhanced with NT particles by processing of larger volume urine samples. Furthermore, we developed a magnetic NT particle, CN3080, based on the same backbone of CN1030, and demonstrated that CN3080 could also capture and enrich ZIKV and CHIKV in a dose-dependent manner. Finally, in silico docking predictions support that the affinity between reactive red 120 and ZIKV or CHIKV envelope proteins appeared to be greater than acrylic acid. Overall, our data show that NT particles along with reactive red 120 can be utilized as a pre-processing technology for enhancement of detecting febrile-illness causing viruses.

EGR1 upregulation following Venezuelan equine encephalitis virus infection is regulated by ERK and PERK pathways contributing to cell death.

Venezuelan equine encephalitis virus (VEEV) is a neurotropic virus that causes significant disease in both humans and equines. Here we characterized the impact of VEEV on signaling pathways regulating cell death in human primary astrocytes. VEEV productively infected primary astrocytes and caused an upregulation of early growth response 1 (EGR1) gene expression at 9 and 18 h post infection. EGR1 induction was dependent on extracellular signal-regulated kinase1/2 (ERK1/2) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), but not on p38 mitogen activated protein kinase (MAPK) or phosphoinositide 3-kinase (PI3K) signaling. Knockdown of EGR1 significantly reduced VEEV-induced apoptosis and impacted viral replication. Knockdown of ERK1/2 or PERK significantly reduced EGR1 gene expression, dramatically reduced viral replication, and increased cell survival as well as rescued cells from VEEV-induced apoptosis. These data indicate that EGR1 activation and subsequent cell death are regulated through ERK and PERK pathways in VEEV infected primary astrocytes.

Fast acquisition abdominal MRI study for the investigation of suspected acute appendicitis in paediatric patients.

OBJECTIVES: To assess the diagnostic accuracy of fast acquisition MRI in suspected cases of paediatric appendicitis presenting to a tertiary referral hospital. MATERIALS AND METHODS: A prospective study was undertaken between May and October 2017 of 52 children who presented with suspected appendicitis and were referred for an abdominal ultrasound. All patients included in this study received both an abdominal ultrasound and five-sequence MRI consisting of axial and coronal gradient echo T2 scans, fat-saturated SSFSE and a diffusion-weighted scan. Participants were randomised into groups of MRI with breath-holds or MRI with free breathing. A patient satisfaction survey was also carried out. Histopathology findings, where available, were used as a gold standard for the purposes of data analysis. Statistical analysis was performed, and p values < 0.05 were considered statistically significant. RESULTS: Ultrasound had a sensitivity and specificity of 25% and 92.9%, respectively. MRI with breath-hold had a sensitivity and specificity of 81.8% and 66.7%, respectively, whilst MRI with free breathing was superior with sensitivity and specificity of 92.3% and 84.2%, respectively. MRI with free breathing was also more time efficient (p < 0.0001). Group statistics were comparable (p < 0.05). CONCLUSIONS: The use of fast acquisition MRI protocols, particularly free breathing sequences, for patients admitted with suspected appendicitis can result in faster diagnosis, treatment and discharge. It also has a statistically significant diagnostic advantage over ultrasound. Additionally, the higher specificity of MR can reduce the number of negative appendectomies performed in tertiary centres.

Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease.

The emergence of SARS-CoV-2 has created an international health crisis, and small animal models mirroring SARS-CoV-2 human disease are essential for medical countermeasure (MCM) development. Mice are refractory to SARS-CoV-2 infection owing to low-affinity binding to the murine angiotensin-converting enzyme 2 (ACE2) protein. Here, we evaluated the pathogenesis of SARS-CoV-2 in male and female mice expressing the human ACE2 gene under the control of the keratin 18 promoter (K18). In contrast to nontransgenic mice, intranasal exposure of K18-hACE2 animals to 2 different doses of SARS-CoV-2 resulted in acute disease, including weight loss, lung injury, brain infection, and lethality. Vasculitis was the most prominent finding in the lungs of infected mice. Transcriptomic analysis from lungs of infected animals showed increases in transcripts involved in lung injury and inflammatory cytokines. In the low-dose challenge groups, there was a survival advantage in the female mice, with 60% surviving infection, whereas all male mice succumbed to disease. Male mice that succumbed to disease had higher levels of inflammatory transcripts compared with female mice. To our knowledge, this is the first highly lethal murine infection model for SARS-CoV-2 and should be valuable for the study of SARS-CoV-2 pathogenesis and for the assessment of MCMs.

Consent and refusal for adolescents: the law.

The media reported last year that a 13-year-old girl had 'won the right' to refuse a heart transplant, which highlighted the issues of the rights of adolescents to consent to and refuse medical treatment. However, the perception that the right of adolescents to refuse health care has changed is a false one. Healthcare decision making for adolescents is an area of particular concern for paediatric nurses, who should attempt to make some sense of the complex legal issues concerning competence, consent and refusal. This article outlines the legal status of adolescents regarding consent to and refusal of treatment, and highlights rulings that have affected them greatly. Nurses must understand and believe in their patients' rights if they are to promote them and act as their advocate.

New World alphavirus protein interactomes from a therapeutic perspective.

The New World alphaviruses, Venezuelan, eastern and western equine encephalitis viruses (VEEV, EEEV, and WEEV), are important human pathogens due to their ability to cause varying levels of morbidity and mortality in humans. There is also concern about VEEV and EEEV being used as bioweapons. Currently, a FDA-approved antiviral is lacking for New World alphaviruses. In this review, the function of each viral protein is discussed with an emphasis on how these functions can be targeted by therapeutics. Both direct acting antivirals as well as inhibitors that impact host protein interactions with viral proteins are described. Non-structural protein 3 (nsP3), capsid, and E2 proteins have garnered attention in recent years, whereas little is known regarding host protein interactions of the other viral proteins and is an important avenue for future study.

Aetiological profile and treatment outcomes of epistaxis at a major teaching hospital: a review of 721 cases.

BACKGROUND: Epistaxis is the most prevalent ENT emergency and a significant burden on ENT services. Our objective was to study the incidence and outcomes of patients presenting with epistaxis at a major teaching hospital. METHODS: A retrospective descriptive study of 721 patients, who presented with epistaxis over a 1-year period, was carried out. Data collected was analysed using SPSS software version 20. RESULTS: Of the 721 patients, initial treatment consisted of nasal cautery (298), nasal packing (200), or no treatment (223). Fifty-nine patients were admitted. The mean age of admitted patients was 66.8 years and the male to female ratio was 2:1. 69.5% had hypertension and 78% used an antiplatelet/anticoagulation medication. The majority of admitted and return patients were out of hours referrals from ED and the mean admission duration was five nights. Surgical treatment for intractable epistaxis included arterial ligation or endovascular embolisation. Successful treatment was defined as no recurrent epistaxis following pack removal or no readmission with epistaxis within 24 h of hospital discharge. Six hundred forty-four patients had successful treatment. CONCLUSION: More return and admitted patients presented at out-of-hours times with less clinical staff on site. Most non-admitted patients received no treatment. These factors possibly lead to increased stress on the ENT casualty service. Cautery and nasal packing are the most common treatment modalities in first-time and admitted patients yet result in considerable rates of representation.

A comparison of clinical- and patient-reported outcomes of the cemented ATTUNE and PFC sigma fixed bearing cruciate sacrificing knee systems in patients who underwent total knee replacement with both prostheses in opposite knees.

BACKGROUND: The ATTUNE Knee by DePuy Synthes was introduced in 2013. It is designed to provide better range of motion and address patient-reported instability. The PFC Sigma Knee, an earlier prosthesis by DePuy Synthes, is a common knee replacement with a strong clinical track record. Our aim is to compare the outcomes after primary total knee replacement for end-stage knee osteoarthritis of the PFC and ATTUNE knee systems in 21 patients who each have prosthesis in opposite knees using WOMAC, Oxford Knee and SF-12 scores and evaluation of range of motion. METHODS: A review was carried out on 21 patients who underwent primary total knee replacement with both the ATTUNE and PFC knee systems. These were staged operations performed in the same institution and by the same surgeon. All cases were followed up for a minimum of 6 months. WOMAC, Oxford Knee and SF-12 scores, as well as knee range of motion were recorded preoperatively and at 6 months postoperatively. RESULTS: There was a significant difference in pre- to 6-month post-operative outcomes in PFC and ATTUNE groups with regard to improvement in range of motion (10° ± 8 and 13° ± 11, respectively). There was also a significant improvement in WOMAC scores (PFC group) and Oxford Knee Scores (ATTUNE group) (8.9 ± 7.7 and 12.1 ± 8.4, respectively). There was a significant improvement in SF-12 Score in both groups (10.1 ± 9.3 for PFC and 15.8 ± 13.3 for ATTUNE). The minimum clinically important difference (MCID) in scoring systems at 6 months was reached by 6 patients in the PFC group and 12 in the ATTUNE group. CONCLUSION: A significant difference was demonstrated in clinical outcome at 6 months postoperatively between PFC and ATTUNE knee systems in patients who underwent total knee arthroplasty with both prostheses. Superior results were recorded for the ATTUNE knee system.

Repurposed FDA-Approved drug sorafenib reduces replication of Venezuelan equine encephalitis virus and other alphaviruses.

The New World alphaviruses -Venezuelan, eastern, and western equine encephalitis viruses (VEEV, EEEV, and WEEV respectively) - cause a febrile disease that is often lethal in equines and children and leads to long-term neurological sequelae in survivors. Endemic to the Americas, epizootic outbreaks of the three viruses occur sporadically in the continental United States. All three viruses aerosolize readily, replicate to high titers in cell culture, and have low infectious doses. Additionally, there are no FDA-approved vaccines or therapeutics for human use. To address the therapeutic gap, a high throughput assay utilizing a luciferase reporter virus, TC83-luc, was performed to screen a library of commercially available, FDA-approved drugs for antiviral activity. From a group of twenty compounds found to significantly decrease luminescence, the carcinoma therapeutic sorafenib inhibited replication of VEEV-TC83 and TrD in vitro. Additionally, sorafenib inhibited replication of EEEV and two Old World alphaviruses, Sindbis virus and chikungunya virus, at 8 and 16 h post-infection. Sorafenib caused no toxicity in Vero cells, and coupled with a low EC50 value, yielded a selectivity index of >19. Mechanism of actions studies suggest that sorafenib inhibited viral translation through dephosphorylation of several key proteins, including eIF4E and p70S6K, leading to a reduction in viral protein production and overall viral replication.

Venezuelan Equine Encephalitis Virus Capsid Implicated in Infection-Induced Cell Cycle Delay in vitro.

Venezuelan equine encephalitis virus (VEEV) is a positive sense, single-stranded RNA virus and member of the New World alphaviruses. It causes a biphasic febrile illness that can be accompanied by central nervous system involvement and moderate morbidity in humans and severe mortality in equines. The virus has a history of weaponization, lacks FDA-approved therapeutics and vaccines in humans, and is considered a select agent. Like other RNA viruses, VEEV replicates in the cytoplasm of infected cells and eventually induces apoptosis. The capsid protein, which contains a nuclear localization and a nuclear export sequence, induces a shutdown of host transcription and nucleocytoplasmic trafficking. Here we show that infection with VEEV causes a dysregulation of cell cycling and a delay in the G0/G1 phase in Vero cells and U87MG astrocytes. Cells infected with VEEV encoding a capsid NLS mutant or treated with the capsid-importin α interaction inhibitor G281-1485 were partially rescued from this cell cycle dysregulation. Pathway analysis of previously published RNA-sequencing data from VEEV infected U87MG astrocytes identified alterations of canonical pathways involving cell cycle, checkpoint regulation, and proliferation. Multiple cyclins including cyclin D1, cyclin A2 and cyclin E2 and other regulators of the cell cycle were downregulated in infected cells in a capsid NLS dependent manner. Loss of Rb phosphorylation, which is a substrate for cyclin/cdk complexes was also observed. These data demonstrate the importance of capsid nuclear localization and/or importin α binding for inducing cell cycle arrest and transcriptional downregulation of key cell cycle regulators.

The impact of sarcopenia and myosteatosis on postoperative outcomes in patients with inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease (IBD) is a relatively common disorder with significant associated morbidity. Sarcopenia and myosteatosis are associated with adverse postoperative outcomes. This study investigated outcomes in IBD patients undergoing surgical resection relative to the presence of sarcopenia and myosteatosis. METHODS: A retrospective analysis of a prospectively maintained surgical database was conducted. All patients undergoing elective or emergency resection for IBD between 2011 and 2016, with a contemporaneous perioperative computed tomography (CT) scan, were included. Patient demographics, clinical and biochemical measurements were collected. Skeletal muscle index and attenuation were measured on perioperative CT scans using Osirix version 5.6.1. Univariate and multivariate regression analysis was used to identify risk factors for adverse postoperative outcomes. RESULTS: Seventy-seven patients (46 male, 31 female; mean age 42 years, range 20-80 years) were included. Thirty patients (30%) had sarcopenia and 26 (34%) had myosteatosis. Myosteatosis was significantly associated with increased hospital stay postoperatively (9 versus 13 days). Sarcopenia and myosteatosis were associated with hospital readmission within 30 days on univariate analysis. Multivariate regression analysis demonstrated an independent association between myosteatosis and hospital readmission. Sixteen patients (21%) had a clinically relevant postoperative complication, but an association with sarcopenia and myosteatosis was not observed. A neutrophil-lymphocyte ratio greater than 5 was predictive of clinically relevant postoperative complications on multivariate regression analysis. CONCLUSIONS: Myosteatosis was associated with increased hospital stay and increased 30-day hospital readmission rates on multivariate regression analysis. Sarcopenia and myosteatosis in IBD were not associated with clinically relevant postoperative complications.

Using body mass index to estimate individualised patient radiation dose in abdominal computed tomography.

BACKGROUND: The size-specific dose estimate (SSDE) is a dose-related metrics that incorporates patient size into its calculation. It is usually derived from the volume computed tomography dose index (CTDIvol) by applying a conversion factor determined from manually measured anteroposterior and lateral skin-to-skin patient diameters at the midslice level on computed tomography (CT) localiser images, an awkward, time-consuming, and not highly reproducible technique. The objective of this study was to evaluate the potential for the use of body mass index (BMI) as a size-related metrics alternative to the midslice effective diameter (DE) to obtain a size-specific dose (SSDE) in abdominal CT. METHODS: In this retrospective study of patients who underwent abdominal CT for the investigation of inflammatory bowel disease, the DE was measured on the midslice level on CT-localiser images of each patient. This was correlated with patient BMI and the linear regression equation relating the quantities was calculated. The ratio between the internal and the external abdominal diameters (DRATIO) was also measured to assess correlation with radiation dose. Pearson correlation analysis and linear regression models were used. RESULTS: There was good correlation between DE and patient BMI (r = 0.88). An equation allowing calculation of DE from BMI was calculated by linear regression analysis as follows: DE = 0.76 (BMI) + 9.4. A weak correlation between radiation dose and DRATIO was demonstrated (r = 0.45). CONCLUSIONS: Patient BMI can be used to accurately estimate DE, obviating the need to measure anteroposterior and lateral diameters in order to calculate a SSDE for abdominal CT.