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Background: Mutations present in emerging SARS-CoV-2 variants permit evasion of neutralization with prototype vaccines. A novel Omicron BA.1 subvariant-specific vaccine (NVX-CoV2515) was tested alone or as a bivalent preparation with the prototype vaccine (NVX-CoV2373) to assess antibody responses to SARS-CoV-2., Methods: Participants aged 18 to 64 years immunized with 3 doses of prototype mRNA vaccines were randomized 1:1:1 to receive a single dose of NVX-CoV2515, NVX-CoV2373, or the bivalent mixture in a phase 3 study investigating heterologous boosting with SARS-CoV-2 recombinant spike protein vaccines. Immunogenicity was measured 14 and 28 days after vaccination for the SARS-CoV-2 Omicron BA.1 sublineage and ancestral strain. Safety profiles of vaccines were assessed., Results: Of participants who received trial vaccine (N = 829), those administered NVX-CoV2515 (n = 286) demonstrated a superior neutralizing antibody response to BA.1 vs NVX-CoV2373 (n = 274) at day 14 (geometric mean titer ratio, 1.6; 95% CI, 1.33-2.03). Seroresponse rates were 73.4% (91/124; 95% CI, 64.7-80.9) for NVX-CoV2515 vs 50.9% (59/116; 95% CI, 41.4-60.3) for NVX-CoV2373. All formulations were similarly well tolerated., Conclusions: NVX-CoV2515 elicited a superior neutralizing antibody response against the Omicron BA.1 subvariant as compared with NVX-CoV2373 when administered as a fourth dose. Safety data were consistent with the established safety profile of NVX-CoV2373., Clinical Trials Registration: ClinicalTrials.gov (NCT05372588)., Competing Interests: Potential conflicts of interest. C. B., E. J. R., W. W., J. S. P., S. C.-C., M. Z., R. K., N. P., A. B., A. M., J. S., G. S., I. C., G. M. G., R. W., and R. M. M. are current or former Novavax employees and as such receive or received a salary for their work and may hold Novavax stock. O. C. and T. M. P. act as investigators at Novatrials on clinical trials and have not received personal financial payment from Novavax. A. M. N. acts as an investigator at AusTrials on clinical trials of COVID-19 and other vaccines sponsored by vaccine manufacturers, including Pfizer, GlaxoSmithKline, Novavax, Seqirus, and Moderna. He receives no personal financial payment for this work. K. C. acts as an investigator at Emeritus Research and has not received any personal financial payment from Novavax. R. M. acts as an investigator at Paratus Clinical Research and has not received any personal financial payment from Novavax. M. B. has received payment or honoraria as well as support for meeting attendance and/or travel from Gilead Sciences and ViiV Healthcare and has received research funding from Gilead Sciences, ViiV Healthcare, GlaxoSmithKline, Merck & Co, Eli Lilly, Amgen, Pfizer, Bristol-Myers Squibb, Novartis, and Sanofi. He has also participated on a data safety monitoring board or advisory board for Gilead Sciences, ViiV Healthcare, and Cymra. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: SARS-CoV-2 variants evade immunity despite vaccination with prototype COVID-19 vaccines or previous infection. The 2019nCoV-311 (part 2) study is evaluating immune responses after two booster doses of a vaccine containing the omicron BA.5 subvariant spike protein in adults previously vaccinated with a prototype mRNA vaccine. This interim analysis reports on day 28 immunogenicity and safety outcomes after one booster dose., Methods: In this phase 3, randomised, observer-blinded study conducted at 35 sites in Australia, medically stable, previously COVID-19-vaccinated (mRNA-based; ≥three doses) adults aged 18 years or older were enrolled and randomly allocated (1:1:1; via an interactive web response system) to receive two doses of bivalent (NVX-CoV2373 + NVX-CoV2540; bivalent group), authorised prototype (NVX-CoV2373; prototype group), or BA.5 (NVX-CoV2540; BA.5 group) vaccine. Only blinded personnel performed study assessments or had participant contact to collect data after study vaccination. Participants received vaccines containing 5 μg SARS-CoV-2 recombinant spike protein and 50 μg Matrix-M adjuvant, administered via a 0·5 mL intramuscular injection (2·5 μg of NVX-CoV2373 plus 2·5 μg of NVX-CoV2540 for the bivalent vaccine, prepared on-site as a 1:1 mixture). The coprimary endpoints include day 28 neutralising antibody geometric mean titre (GMT) ratios (GMTRs) to omicron BA.5 and the ancestral strain, and seroresponse rates to BA.5, in the bivalent and prototype groups. These endpoints were calculated in the per-protocol analysis set, which was defined as participants who had received a vaccine dose, had baseline and day 28 immunogenicity data, and were PCR-negative for SARS-CoV-2, with no major protocol deviations. The primary objective was to determine the primary outcome (antibody responses), which consisted of three comparisons: superiority of the bivalent versus prototype vaccine for neutralising antibody GMT to BA.5 (ie, lower bound of the GMTR 95% CI >1·0); non-inferiority of neutralising antibody seroresponse rate to BA.5 (ie, lower bound of the seroresponse rate 95% CI >-5%); and non-inferiority of neutralising antibody GMT to the ancestral strain (ie, lower bound of GMTR 95% CI >0·67). This trial was registered at ClinicalTrials.gov, number NCT05372588., Findings: Between March 22, 2023 and May 2, 2023, 837 participants were screened for eligibility and 766 were randomly allocated to receive the BA.5 (n=255), prototype (n=252), or bivalent (n=259) vaccine. After accounting for exclusions due to participants being baseline SARS-CoV-2-positive, having previous infection, or protocol deviations, the per-protocol analysis set included 694 participants (236 in BA.5 group, 227 in prototype group, and 231 in bivalent group). In this interim analysis (maximum follow-up 35 days after the first dose), the bivalent group, compared with the prototype group, had superior neutralising antibody responses to BA.5 (GMT 1017·8 [95% CI 891·0-1162·6] vs 515·1 [450·4-589·0]; GMTR 2·0 [1·69-2·33]) and a non-inferior seroresponse rate to BA.5 at day 28 (39·8% [33·5-46·5] vs 12·3% [8·4-17·3]; difference 27·5% [19·8-35·0]). The bivalent group also had non-inferior neutralising antibody responses to the ancestral strain (GMTR 1·0 [0·84-1·20]), compared with the prototype group. All vaccines were similarly well tolerated., Interpretation: All three coprimary endpoints were met in part 2 of the ongoing 2019nCoV-311 study. These data support the development of monovalent and/or bivalent vaccines for the most currently circulating variants, to optimise protection. With no new safety findings, further investigation of omicron-based subvariant vaccines is supported by the evidence., Funding: Novavax., Competing Interests: Declaration of interests CB, WW, JSP, SC-C, MZ, RK, NP, AM, JS, GS, IC, RW, and RMM are current Novavax employees and as such receive a work salary and hold Novavax stock. GMG is a former employee and current consultant for Novavax and holds Novavax stock. OC and TMP act as investigators at Novatrials on clinical trials. AMN acts as an investigator at AusTrials on clinical trials of COVID-19 and other vaccines sponsored by vaccine manufacturers, including Pfizer, GlaxoSmithKline, Novavax, Seqirus, and Moderna; he receives no personal financial payment for this work. KC acts as an investigator at Emeritus Research. RM acts as an investigator at Paratus Clinical Research. OC, TMP, KC, and RM have not received any personal financial payment from Novavax. MB has received payment or honoraria as well as support for meeting attendance or travel, or both, from Gilead Sciences and ViiV Healthcare, and his institution has received research funding from Gilead Sciences, ViiV Healthcare, GlaxoSmithKline, Merck & Co, Eli Lilly, Amgen, Pfizer, Bristol-Myers Squibb, Novartis, Biotron, Cymra, and Eyegene; his institution has received payment for his participation on a data safety monitoring board for Eyegene and Cymra, whereas he has received payment for advisory board attendance for Gilead Sciences and ViiV Healthcare. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Objectives: General practitioners (GPs) play a central role in healthcare, serving as the first point of contact, making appropriate referrals and coordinating care for chronic conditions such as heart failure (HF). We sought to determine healthcare use by people with HF in primary care., Method: In this Study of Heart failure in the Australian Primary carE setting (SHAPE), we analysed records of 1.93 million adult patients who attended a total of 43 practices between 1 July 2013 and 30 June 2018. We identified and examined the data of 20,219 patients with HF to describe the frequency of visits and use of Medicare Benefits Schedule items., Results: Patients with HF saw GPs 14.4 times per annum on average; 59.5% had a General Practice Management Plan (GPMP), 2.9% of GPMPs were reviewed annually or more frequently, and 46.8% of patients had been referred to a cardiologist. A total of 3761 had coexisting anxiety or depression, and of these 37.1% had a mental health plan., Discussion: Patients with HF visit their GP frequently, with many not reaching guideline therapy nor referred to cardiologists. Low use of care planning and reviews presents an opportunity for GPs to improve care.

Aims: Heart failure (HF) causes significant morbidity and mortality, but the rates and characteristics of people with HF in Australia are not well studied. SHAPE set out to describe the characteristics of HF patients seen in the real-world setting., Methods: We analysed anonymized patient data extracted from the clinical software of 43 participating GP clinics for the 5 year period from 1 July 2013 to 30 June 2018. Patients were stratified into 'definite' and 'probable' HF based on a hierarchy of selection criteria and analysed for their clinical characteristics. Symptoms and signs of HF and ejection fraction data were searched for within the free text of the medical notes., Results: Of the 1.12 million adults seen regularly, 20 219 were classified as having definite or probable HF. The mean age of the population was 69.8 years, 50.6% were female, and mean body mass index was 31.2 kg/m 2 . Fewer than 1 in 6 had the HF diagnosis optimally recorded. Only 3.2% (650 patients) had their left ventricular ejection fraction (EF) quantified: 40.9% had an EF ≥50% and 59.1% had an EF <50%. The most common comorbidities in people with HF were hypertension (41.1%), chronic obstructive pulmonary disease/asthma (25.1%) and depression/anxiety (18.4%). Hypotension (2.3%), bradycardia (6.3%), severe renal impairment (6.4%) and hyperkalaemia (2.0%) were uncommon. Just over one-third (37.8%) had iron deficiency. Loop diuretic use was common (56.7%) but only 33.7% were on a guideline recommended beta-blockers. Use of ivabradine (1.4%) and sacubitril/valsartan (1.2%) was very low, while 39.9% had been prescribed an angiotensin-converting enzyme inhibitor, 31.6% an angiotensin receptor blocker and 16.0% spironolactone. Many patients were prescribed medications that may worsen HF or are relatively contraindicated, such as macrolide antibiotics (29.9%), corticosteroids (25.8%), nonsteroidal anti-inflammatory drugs (23.9%), and tricyclic antidepressants (9.4%)., Conclusions: Heart failure is poorly documented in general practice records and may be contributing to untoward downstream effects, such as low documentation of echocardiography, poor use of guideline recommended therapies and frequent use of medications that may worsen HF., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: The currently licensed quadrivalent MenACWY-CRM conjugate vaccine presentation consists of two vials (lyophilised MenA and liquid MenCWY) to be reconstituted before injection. A new fully liquid formulation in a single vial has been developed to further improve the vaccine presentation. Since the MenA structure is subject to hydrolytic degradation, this study was conducted to compare the immunogenicity and safety of the investigational MenACWY-CRM liquid vaccine with the licensed vaccine., Methods: In this multicentre, randomised, controlled, observer-blind, phase 2b study, 979 healthy adults were administered a single dose of MenACWY-CRM liquid presentation or the currently licensed MenACWY-CRM vaccine. MenA free saccharide generation was accelerated to approximately 30% in the liquid presentation and MenA polysaccharide O-acetylation was reduced to approximately 40%, according to a controlled procedure. Immunological non-inferiority of the MenACWY-CRM liquid to the licensed vaccine, as measured by human serum bactericidal assay (hSBA) geometric mean titres (GMTs) against MenA 1 month post-vaccination, was the primary study objective. Safety assessment was among the secondary objectives., Results: Immune responses against each serogroup were similar between the two vaccine groups and was non-inferior for MenA. Adjusted hSBA GMTs for MenA were 185.16 and 211.33 for the MenACWY-CRM liquid presentation and currently licensed vaccine presentation, respectively. The between-group ratio of hSBA GMTs for MenA was 0.88, with a two-sided 95% confidence interval lower limit of 0.64, greater than the prespecified non-inferiority margin of 0.5, thus meeting the primary study objective. Both vaccines were well tolerated. No serious adverse events were considered related to vaccination., Conclusions: The levels of MenA free saccharide and polysaccharide O-acetylation did not affect the immunogenicity of the fully liquid presentation, which was demonstrated to be non-inferior to the immunogenicity of the currently licensed MenACWY-CRM vaccine against MenA. The immunogenicity, reactogenicity and safety profiles of the two vaccine presentations were similar., Competing Interests: Declaration of Competing Interest TA, SVH, MA, BK, BdW, GFDD, MC, PVS, EF, ML and MP are employed by the GSK group of companies. TA, MA, BdW, PVS, EF, ML and MP hold shares in the GSK group of companies. CV reports her institution received payments from the GSK group of companies, MSD and Pfizer, outside the submitted work. ILR reports her institution received payments from the GSK group of companies for the conduct of the study. TN reports payments from the GSK group of companies, Merck, Sanofi Pasteur and Seqirus, outside the submitted work. TA, SVH, MA, BK, BdW, GFDD, MC, PVS, EF, ML, MP, CV, ILR and TN declare no other financial and non-financial relationships and activities. JV, TS, GG, MF, GI, TFS, AMN and SC declare no financial and non-financial relationships and activities and no conflicts of interest., (Copyright © 2021 GlaxoSmithKline Biologicals S.A. Published by Elsevier Ltd.. All rights reserved.)

Aims: At present, there is no robust information on the prevalence and incidence of heart failure (HF) in the general Australian community. The present study of primary care data sought to estimate the prevalence and incidence of HF in the community and to describe the demographic and clinical profile of Australians with HF., Methods and Results: We undertook a retrospective cohort study based on analysis of anonymized medical records of adult patients cared for at 43 Australian general practices between 1 July 2013 and 30 June 2018. Data were extracted from coded and uncoded fields in electronic medical records. The prevalence and annual incidence of HF were calculated, along with 95% confidence intervals, using the 'active' population of people who were regular attenders at the practices. Age-standardized estimates were also derived using the 2017 Australian population as reference. The mean age of the population with HF was 69.8 years, 50.6% were female, and mean body mass index was 31.2 kg/m 2 . The age-standardized prevalence was 2.199% [95% confidence interval (CI): 2.168-2.23%], and the age-standardized annual incidence was 0.348% (95% CI: 0.342-0.354%). These estimates accord with almost 420 000 people living with HF in Australia in 2017, and >66 000 new cases of HF occurring that year. Only 18.9% of patients with definite HF had this formally captured as a 'diagnosis' in their medical record. HF was more frequent among those of lower socio-economic status., Conclusions: HF is common in Australia. The majority of HF patients do not have this diagnosis optimally noted in their primary care medical records., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: There is a paucity of information on the epidemiology of heart failure (HF) in Australia. The Study of Heart failure in the Australian Primary carE setting (SHAPE) study aims to estimate the prevalence and annual incidence of HF in the general Australian community and to describe the demographic and key clinical profile of Australians with HF., Methods: We undertook a retrospective cohort study based on analysis of non-identifiable medical records of adult patients cared for at 43 general practices between 1 July 2013 and 30 June 2018. Data were extracted from coded (diagnosis, pathology and prescription fields) and uncoded fields (clinical notes) in the medical records. The latter searches of free text looked for common synonyms relevant to HF. The population was stratified into three groups based on a hierarchy of selection criteria: (1) definite HF, (2) probable HF and (3) possible HF. The prevalence and annual incidence of HF were calculated, along with 95% confidence intervals., Results: The practices provided care to 2.3 million individual patients over the five-year study period, of whom 1.93 million were adults and 1.12 million were regular patients. Of these patients 15,468 were classified as having 'definite HF', 4751 as having 'probable HF' and 33,556 as having 'possible HF'. A further 39,247 were identified as having an aetiological condition associated with HF. A formal HF diagnosis, HF terms recorded as text in the notes and HF-specific medication were the most common methods to identify 'definite' HF patients. Typical signs and symptoms in combination with a diuretic prescription was the most common method to identify 'probable HF' patients. The majority of 'possible' HF patients were identified by the presence of 2 or more of the typical signs or symptoms. Dyspnoea was the commonest recorded symptom and an elevated jugular venous pressure the commonest recorded sign., Conclusions: This novel approach to undertaking retrospective research of primary care data successfully analysed a combination of coded and uncoded data from the electronic medical records of patients routinely managed in the GP setting. SHAPE is the first real-world study of the epidemiology of HF in the general Australian community setting.

Evidence suggests that patient-centred medical home (PCMH) is more effective than standard general practitioner care in improving patient outcomes in primary care. This paper reports on the design, early implementation experiences, and early findings of the 12-month PCMH model called 'WellNet' delivered across six primary care practices in Sydney, Australia. The WellNet study sample comprises 589 consented participants in the intervention group receiving enhanced primary care in the form of patient-tailored chronic disease management plan, improved self-management support, and regular monitoring by general practitioners (GPs) and trained clinical coordinators. The comparison group consisted of 7750 patients who were matched based on age, gender, type and number of chronic diseases who received standard GP care. Data collected include sociodemographic characteristics, clinical measures, and self-reported health assessments at baseline and 12 months. Early study findings show the mean age of the study participants was 70 years with nearly even gender distribution of males (49.7%) and females (50.3%). The most prevalent chronic diseases in descending order were circulatory system disorders (69.8%), diabetes (47.4%), musculoskeletal disorders (43.5%), respiratory diseases (28.7%), mental illness (18.8%), and cancer (13.6%). To our knowledge, the WellNet study is the first study in Australia to generate evidence on the feasibility of design, recruitment, and implementation of a comprehensive PCMH model. Lessons learned from WellNet study may inform other medical home models in Australian primary care settings.

PDGF-CC is a member of the platelet-derived growth factor (PDGF) family that stimulates PDGFRα phosphorylation and thereby activates intracellular signalling events essential for development but also in cancer, fibrosis and neuropathologies involving blood-brain barrier (BBB) disruption. In order to elucidate the biological and pathological role(s) of PDGF-CC signalling, we have generated high affinity neutralizing monoclonal antibodies (mAbs) recognizing human PDGF-CC. We determined the complementarity determining regions (CDRs) of the selected clones, and mapped the binding epitope for clone 6B3. Using the monoclonal 6B3, we determined the expression pattern for PDGF-CC in different human primary tumours and control tissues, and explored its ability to neutralize PDGF-CC-induced phosphorylation of PDGFRα. In addition, we showed that PDGF-CC induced disruption of the blood-retinal barrier (BRB) was significantly reduced upon intraperitoneal administration of a chimeric anti-PDGF-CC antibody. In summary, we report on high affinity monoclonal antibodies against PDGF-CC that have therapeutic efficacy in vivo., Competing Interests: H.L., A.M.S., L.A. and U.E. have submitted a patent application (Methods and compositions for PDGF-CC inhibition, PCT/US2017/040170) on these antibodies. A.M.S. and U.E. are shareholders of a company (Paracrine Therapeutics AB), developing these antibodies. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: At present, it is difficult to predict which patients with ductal carcinoma-in-situ (DCIS) will subsequently develop frank invasive breast cancer (IDC). A recent survey by our group has shown that NY-ESO-1 and MAGEA are both expressed in DCIS. This study was aimed at determining whether expression of these antigens was related to the later development of IDC., Results: 14 of 42 (33%) of patients developed invasive breast cancer during the follow up period. Only one of those DCIS cases that relapsed was positive for NYESO-1 at diagnosis. In contrast, DCIS samples of 15 of the 28 (54%) of those patients who remained disease-free expressed NY-ESO-1. (Permutation chi square p=0.0033)., Methods: We identified 42 patients with DCIS, and followed them up for more than 10 years. NY-ESO-1 and MAGEA were demonstrated by immunostaining as were CD8+ infiltrates on all sections together with the conventional markers, ER, PR, and HER2., Conclusions: Expression of NY-ESO-1 may predict those patients who will not subsequently develop invasive breast cancer and could therefore potentially be helpful in defining prognosis in patients with DCIS., Competing Interests: CONFLICTS OF INTEREST Raoul C. Coombes declares that he has no conflict of interest. Otavia L. Caballero declares that she has no conflict of interest, Sami. Shousha declares that he has no conflict of interest. Sadaf Ghaem-Maghami declares that she has no conflict of interest, Laura Woodley-Barker declares that she has no conflict of interest. Charlotte S. Wilhelm-Benartzi declares that she has no conflict of interest, and A Munro Neville declares that he has no conflict of interest.

Periostin (POSTN), a secreted homodimeric protein that binds integrins αvβ3, αvβ5, and α6β4, was originally found to be expressed in fetal tissues and in the adult upon injury particularly bone fractures due to its role in remodelling and repair. Recently it was found to be over-expressed in human breast cancer and a variety of other tumour types including head and neck squamous cell carcinoma, where its overexpression correlates with increased tumour invasion. Progress in studying its functional role in tumour pathogenesis has been hampered by the paucity of antibodies for its specific and sensitive detection. It has proven very difficult to obtain monoclonal antibodies (mAbs) against this highly conserved protein but we report here that combining infection of mice with lactate dehydrogenase elevating virus (LDV), a B cell activating arterivirus, with conjugation of human POSTN to ovalbumin as an immunogenic carrier, enabled us to develop six mAbs recognizing both human and mouse POSTN and inhibiting its binding to αvβ3 integrin. Two of the mAbs, MPB4B1 and MPC5B4, were tested and found to inhibit POSTN-induced migration of human endothelial colony forming cells. All six mAbs recognized amino acids 136-51 (APSNEAWDNLDSDIRR) within the POSTN fascilin (FAS) 1-1 domain revealing the functional importance of this motif; this was further highlighted by the ability of aa 136-151 peptide to inhibit integrin-mediated cell migration. Immunohistochemistry using MPC5B4, indicated that breast tumour cell POSTN expression was a strong prognostic indicator, along with tumour size, lymph node, and human epidermal growth factor receptor 2 (HER2) status., (© 2015 UICC.)

Purpose: The aim of this study was to evaluate oncologists' opinions about the use of ionizing radiation in medical imaging of oncology patients., Methods: An electronic survey was e-mailed to 2,725 oncologists at the top 50 National Cancer Institute-funded cancer centers. The survey focused on opinions on CT dose reduction in oncology patients and current philosophies behind long-term imaging in these patients., Results: The response rate was 15% (415 of 2,725). Eighty-two percent of respondents stated that their patients or families have expressed anxiety regarding radiation dose from medical imaging. Although fewer than half of oncologists (48%) did not know whether CT dose reduction techniques were used at their institutions, only 25% were concerned that small lesions may be missed with low-dose CT techniques. The majority of oncologists (63%) follow National Comprehensive Cancer Network guidelines for imaging follow-up, while the remainder follow other national guidelines such as those of the Children's Oncology Group, the American Society of Clinical Oncology, or clinical trials. Ninety percent of respondents believe that long-term surveillance in oncology patients is warranted, particularly in patients with breast cancer, melanoma, sarcoma, and pediatric malignancies. The majority of oncologists would consider the use of low-dose CT imaging in specific patient populations: (1) children and young women, (2) those with malignancies that do not routinely metastasize to the liver, and (3) patients undergoing surveillance imaging., Conclusions: Cumulative radiation exposure is a concern for patients and oncologists. Among oncologists, there is support for long-term imaging surveillance despite lack of national guidelines., (Published by Elsevier Inc.)

Cancer/testis (CT) genes represent a unique class of genes, which are expressed by germ cells, normally silenced in somatic cells, but activated in various cancers. CT proteins can elicit spontaneous immune responses in cancer patients and this feature makes them attractive targets for immunotherapy-based approaches. We have previously reported that CTs are relatively commonly expressed in estrogen receptor (ER) negative, high risk carcinomas. In this study, we examined the expression of selected CT genes in ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS) and benign proliferative lesions of the breast. ER negative DCIS were found to be associated with significant CT gene expression together with HER2 positivity and a marked stromal immune response.

Aim: Patients with rectal cancer often undergo multiple CT scans prior to surgical resection. We propose that in patients with locally advanced rectal cancer without evidence of metastatic disease at presentation, CT imaging of the chest and abdomen after preoperative neoadjuvant therapy does not change clinical information or surgical management., Method: An institutional review board-approved medical record review identified patients with contrast enhanced CT of the chest, abdomen and pelvis alone or in conjunction with (18)F-fluoro-2-deoxy-d-glucose/positron emission tomography imaging for staging of rectal cancer prior to and after neoadjuvant therapy. Eighty-eight patients were included in the study. Scans were reviewed for the presence of metastatic disease on initial and follow-up imaging prior to surgical resection., Results: Seventy-six (86%) of 88 patients had no evidence of metastasis at presentation. None of these patients developed metastatic disease after neoadjuvant therapy. Twelve (14%) had metastases at presentation. No study patient developed metastatic disease in a new organ., Conclusion: Imaging after preoperative neoadjuvant therapy in rectal cancer does not change the designation of metastatic disease. Patients with locally advanced rectal adenocarcinoma without evidence of metastases may not benefit from repeat imaging of the chest and abdomen after neoadjuvant therapy., (Colorectal Disease © 2013 The Association of Coloproctology of Great Britain and Ireland.)

Objective: Evaluate the image quality and diagnostic performance of a free-breathing 3D-gradient-echo sequence with radial acquisition (rGRE) compared with a Cartesian breath-hold 3D-GRE (cGRE) sequence on hepatobiliary phase MRI in patients with breath-holding difficulties., Methods: Twenty-eight consecutive patients (15 males; mean age 61 ± 11.9 years) were analysed in this retrospective IRB-approved study. Breath-holding difficulties during gadoxetate-disodium-enhanced liver MRI manifested as breathing artefacts during dynamic-phase imaging. MRI included axial and coronal cGRE and a radially sampled rGRE sequence during the hepatobiliary phase. Two radiologists independently evaluated cGRE and rGRE images for image quality, liver lesion detection and conspicuity, and bile duct conspicuity on a four-point scale., Results: Liver edge sharpness was significantly higher on rGRE images (P < 0.001). Overall image quality was slightly but significantly higher for rGRE than for cGRE (P < 0.001 and P = 0.039). Bile duct conspicuity scores of rGRE and cGRE were not significantly different. Sensitivity for detection of the 26 liver lesions was similar for rGRE and cGRE (81-77 % and 73-77 %, P = 0.5 and 1.0). Lesion conspicuity scores were significantly higher for rGRE for one reader (P = 0.012)., Conclusion: In patients with breath-holding difficulties, overall image quality and liver lesion conspicuity on hepatobiliary phase MRI can be improved using the rGRE sequence., Key Points: • Patients with diminished breath-holding capacities present a major challenge in abdominal MRI. • A free-breathing sequence for hepatobiliary-phase MRI can improve image quality. • Further advances are needed to reduce acquisition time of the free-breathing gradient-echo sequence.

Purpose: Patients with recurrent nephrolithiasis are often evaluated and followed with computerized tomography. Obesity is a risk factor for nephrolithiasis. We evaluated the radiation dose of computerized tomography in obese and nonobese adults., Materials and Methods: We scanned a validated, anthropomorphic male phantom according to our institutional renal stone evaluation protocol. The obese model consisted of the phantom wrapped in 2 Custom Fat Layers (CIRS, Norfolk, Virginia), which have been verified to have the same radiographic tissue density as fat. High sensitivity metal oxide semiconductor field effect transistor dosimeters were placed at 20 organ locations in the phantoms to measure organ specific radiation doses. The nonobese and obese models have an approximate body mass index of 24 and 30 kg/m(2), respectively. Three runs of renal stone protocol computerized tomography were performed on each phantom under automatic tube current modulation. Organ specific absorbed doses were measured and effective doses were calculated., Results: The bone marrow of each model received the highest dose and the skin received the second highest dose. The mean ± SD effective dose for the nonobese and obese models was 3.04 ± 0.34 and 10.22 ± 0.50 mSv, respectively (p <0.0001)., Conclusions: The effective dose of stone protocol computerized tomography in obese patients is more than threefold higher than the dose in nonobese patients using automatic tube current modulation. The implication of this finding extends beyond the urological stone population and adds to our understanding of radiation exposure from medical imaging., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate the ability of staging computed tomography (CT) without bowel preparation to accurately localize colonic tumors compared to optical colonoscopy., Methods: The local institutional review board approved this retrospective and HIPAA-compliant study. Forty-six patients with colonic adenocarcinoma, preoperative colonoscopy, and staging CT within 60 days of resection were included. Patients underwent contrast enhanced CT imaging without bowel preparation or oral contrast. The colon was divided into four segments with the operative reports used as the standard. Rectal and cecal cancers were excluded. CT scans were reviewed by 5 readers in a segmental binary fashion using a 5-point confidence scale in two sessions blinded and unblinded to the colonoscopy report., Results: At surgery 49 tumors were found in 46 patients. Readers detected 86.1%, 74.3%, and 66.9% of lesions with 92.0%, 94.1%, and 95.4% accuracy for confidence scores of ≥ 3, ≥ 4, and 5. CT interobserver agreement was good (κ=0.82) for the unblinded and moderate (κ=0.60) for the blinded read. Colonoscopic localization was only 78.7% accurate with 2 tumors undiscovered. Colonoscopic accuracy was low in the descending colon (57.1%) and the transverse colon (55.6%)., Conclusions: Preoperative staging CT is more accurate than colonoscopy in the localization of colonic tumors., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)