Development of a multi-task learning V-Net for pulmonary lobar segmentation on CT and application to diseased lungs.

AIM: To develop a multi-task learning (MTL) V-Net for pulmonary lobar segmentation on computed tomography (CT) and application to diseased lungs. MATERIALS AND METHODS: The described methodology utilises tracheobronchial tree information to enhance segmentation accuracy through the algorithm's spatial familiarity to define lobar extent more accurately. The method undertakes parallel segmentation of lobes and auxiliary tissues simultaneously by employing MTL in conjunction with V-Net-attention, a popular convolutional neural network in the imaging realm. Its performance was validated by an external dataset of patients with four distinct lung conditions: severe lung cancer, COVID-19 pneumonitis, collapsed lungs, and chronic obstructive pulmonary disease (COPD), even though the training data included none of these cases. RESULTS: The following Dice scores were achieved on a per-segment basis: normal lungs 0.97, COPD 0.94, lung cancer 0.94, COVID-19 pneumonitis 0.94, and collapsed lung 0.92, all at p<0.05. CONCLUSION: Despite severe abnormalities, the model provided good performance at segmenting lobes, demonstrating the benefit of tissue learning. The proposed model is poised for adoption in the clinical setting as a robust tool for radiologists and researchers to define the lobar distribution of lung diseases and aid in disease treatment planning.

Fully automated deep-learning section-based muscle segmentation from CT images for sarcopenia assessment.

AIM: To develop a fully automated deep-learning-based approach to measure muscle area for assessing sarcopenia on standard-of-care computed tomography (CT) of the abdomen without any case exclusion criteria, for opportunistic screening for frailty. MATERIALS AND METHODS: This ethically approved retrospective study used publicly available and institutional unselected abdominal CT images (n=1,070 training, n=31 testing). The method consisted of two sequential steps: section detection from CT volume followed by muscle segmentation on single-section. Both stages used fully convolutional neural networks (FCNN), based on a UNet-like architecture. Input data consisted of CT volumes with a variety of fields of view, section thicknesses, occlusions, artefacts, and anatomical variations. Output consisted of segmented muscle area on a CT section at the L3 vertebral level. The muscle was segmented into erector spinae, psoas, and rectus abdominus muscle groups. Output was tested against expert manual segmentation. RESULTS: Threefold cross-validation was used to evaluate the model. Section detection cross-validation error was 1.41 ± 5.02 (in sections). Segmentation cross-validation Dice overlaps were 0.97 ± 0.02, 0.95 ± 0.04, and 0.94 ± 0.04 for erector spinae, psoas, and rectus abdominus, respectively, and 0.96 ± 0.02 for the combined muscle area, with R2 = 0.95/0.98 for muscle attenuation/area in 28/31 hold-out test cases. No statistical difference was found between the automated output and a second annotator. Fully automated processing took <1 second per CT examination. CONCLUSIONS: A FCNN pipeline accurately and efficiently automates muscle segmentation at the L3 vertebral level from unselected abdominal CT volumes, with no manual processing step. This approach is promising as a generalisable tool for opportunistic screening for frailty on standard-of-care CT.

Introduction to the National Cancer Imaging Translational Accelerator (NCITA): a UK-wide infrastructure for multicentre clinical translation of cancer imaging biomarkers.

The National Cancer Imaging Translational Accelerator (NCITA) is creating a UK national coordinated infrastructure for accelerated translation of imaging biomarkers for clinical use. Through the development of standardised protocols, data integration tools and ongoing training programmes, NCITA provides a unique scalable infrastructure for imaging biomarker qualification using multicentre clinical studies.

Health and motivation as mediators of the effects of job demands, job control, job support, and role conflicts at work and home on sickness presenteeism and absenteeism.

PURPOSE: The first objective was to contribute to a better understanding of the contrasting and paradoxical results in studies of work environment factors and sickness presence and sickness absence. A second objective was to examine if, and under what conditions, employees choose to replace sickness absence with sickness presence, i.e., so-called substitution. METHODS: The study utilizes a large body of cross-sectional questionnaire data (n = 130,161) gathered in Sweden from 2002 to 2007 in connection with a comprehensive health promotion initiative. Health and motivation were analyzed as mediators of the effects of five job factors, job control, job support, job demand, role conflict and "work to family conflict" on sickness presence and absence. RESULTS: The results concerning job demands indicate substitution in that increased job demands are associated with increased presenteeism and reduced absenteeism. The direct effect of higher job support was increased absenteeism, but via the health and motivation paths, the total effect of more social support was health-promoting and associated with a reduction in sickness absence and sickness presence. High job control emerged as the most pronounced health-promoting factor, reducing sickness presenteeism as well as absenteeism. More role conflicts and work-to-family conflicts were directly and indirectly associated with decreased health and increased absenteeism as well as presenteeism. earlier research. CONCLUSION: The mediation analyzes shed light on some of the paradoxes in research on sickness presenteeism and sickness absenteeism, especially regarding job demands and job support. The substitution effect is important for workplace policy and occupational health practice.

Machine learning in whole-body MRI: experiences and challenges from an applied study using multicentre data.

Machine learning is now being increasingly employed in radiology to assist with tasks such as automatic lesion detection, segmentation, and characterisation. We are currently involved in an National Institute of Health Research (NIHR)-funded project, which aims to develop machine learning methods to improve the diagnostic performance and reduce the radiology reading time of whole-body magnetic resonance imaging (MRI) scans, in patients being staged for cancer (MALIBO study). We describe here the main challenges we have encountered during the course of this project. Data quality and uniformity are the two most important data traits to be considered in clinical trials incorporating machine learning. Robust data pre-processing and machine learning pipelines have been employed in MALIBO, a task facilitated by the now freely available machine learning libraries and toolboxes. Another important consideration for achieving the desired clinical outcome in MALIBO, was to effectively host the resulting machine learning output, along with the clinical images, for reading in a clinical environment. Finally, a range of legal, ethical, and clinical acceptance issues should be considered when attempting to incorporate computer-assisting tools into clinical practice. The road from translating computational methods into potentially useful clinical tools involves an analytical, stepwise adaptation approach, as well as engagement of a multidisciplinary team.

Repeatability of quantitative 18F-FLT uptake measurements in solid tumors: an individual patient data multi-center meta-analysis.

INTRODUCTION: 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) positron emission tomography (PET) provides a non-invasive method to assess cellular proliferation and response to antitumor therapy. Quantitative 18F-FLT uptake metrics are being used for evaluation of proliferative response in investigational setting, however multi-center repeatability needs to be established. The aim of this study was to determine the repeatability of 18F-FLT tumor uptake metrics by re-analyzing individual patient data from previously published reports using the same tumor segmentation method and repeatability metrics across cohorts. METHODS: A systematic search in PubMed, EMBASE.com and the Cochrane Library from inception-October 2016 yielded five 18F-FLT repeatability cohorts in solid tumors. 18F-FLT avid lesions were delineated using a 50% isocontour adapted for local background on test and retest scans. SUVmax, SUVmean, SUVpeak, proliferative volume and total lesion uptake (TLU) were calculated. Repeatability was assessed using the repeatability coefficient (RC = 1.96 × SD of test-retest differences), linear regression analysis, and the intra-class correlation coefficient (ICC). The impact of different lesion selection criteria was also evaluated. RESULTS: Images from four cohorts containing 30 patients with 52 lesions were obtained and analyzed (ten in breast cancer, nine in head and neck squamous cell carcinoma, and 33 in non-small cell lung cancer patients). A good correlation was found between test-retest data for all 18F-FLT uptake metrics (R2 ≥ 0.93; ICC ≥ 0.96). Best repeatability was found for SUVpeak (RC: 23.1%), without significant differences in RC between different SUV metrics. Repeatability of proliferative volume (RC: 36.0%) and TLU (RC: 36.4%) was worse than SUV. Lesion selection methods based on SUVmax ≥ 4.0 improved the repeatability of volumetric metrics (RC: 26-28%), but did not affect the repeatability of SUV metrics. CONCLUSIONS: In multi-center studies, differences ≥ 25% in 18F-FLT SUV metrics likely represent a true change in tumor uptake. Larger differences are required for FLT metrics comprising volume estimates when no lesion selection criteria are applied.

Histogram analysis of apparent diffusion coefficient from whole-body diffusion-weighted MRI to predict early response to chemotherapy in patients with metastatic colorectal cancer: preliminary results.

AIM: To evaluate apparent diffusion coefficient (ADC) histogram analysis parameters, acquired from whole-body diffusion-weighted magnetic resonance imaging (DW-MRI), as very early predictors of response to chemotherapy in patients with metastatic colorectal cancer (mCRC). MATERIALS AND METHODS: This was a single-institution prospective study, approved by the West Midlands-South Birmingham research ethics committee. All patients gave fully informed consent prior to imaging. Sixteen patients with histologically confirmed mCRC were enrolled to the study and 11 were successfully scanned with whole-body DW-MRI before (baseline) and 10.8±2.7 days after commencing chemotherapy (follow-up). Therapy response was assessed by RECIST 1.1. Mean ADC and histogram parameters (skewness, kurtosis, 25th, 50th, and 75th percentiles) were compared between progressors and non-progressors at baseline and follow-up. Receiver operating characteristics (ROC) analysis was performed for the statistically significant parameters. Data from metastases were also compared to normative tissue data acquired from healthy volunteers. RESULTS: Three patients had progressive disease (progressors) and eight had partial response/stable disease (non-progressors). Mean, 25th, 50th, and 75th percentiles were significantly lower for progressors at baseline (p=0.012, 0.012, 0.012 and 0.025 respectively) with areas under the ROC curves (AUC)=0.58, 0.50, 0.58 and 0.63, respectively. Skewness and kurtosis were significantly lower for non-progressors at follow-up (p=0.001 and 0.003 respectively) with AUC=0.67 and 0.79 respectively. CONCLUSION: ADC histogram analysis shows potential in discriminating progressive from non-progressive disease in patients with mCRC, who underwent whole-body DW-MRI. The technique can potentially be tested as a response assessment methodology in larger trials.

Validity and test-retest reliability of an at-work production loss instrument.

BACKGROUND: Besides causing ill health, a poor work environment may contribute to production loss. Production loss assessment instruments emphasize health-related consequences but there is no instrument to measure reduced work performance related to the work environment. AIMS: To examine convergent validity and test-retest reliability of health-related production loss (HRPL) and work environment-related production loss (WRPL) against a valid comparable instrument, the Health and Work Performance Questionnaire (HPQ). METHODS: Cross-sectional study of employees, not on sick leave, who were asked to self-rate their work performance and production losses. Using the Pearson correlation and Bland and Altman's Test of Agreement, convergent validity was examined. Subgroup analyses were performed for employees recording problem-specific reduced work performance. Consistency of pairs of HRPL and WRPL for samples responding to both assessments was expressed using Intraclass Correlation Coefficient (ICC) and tests of repeatability. RESULTS: A total of 88 employees participated and 44 responded to both assessments. Test of agreement between measurements estimates a mean difference of 0.34 for HRPL and -0.03 for WRPL compared with work performance. This indicates that the production loss questions are valid and moderately associated with work performance for the total sample and subgroups. ICC for paired HRPL assessments was 0.90 and 0.91 for WRPL, i.e. the test-retest reliability was good and suggests stability in the instrument. CONCLUSIONS: HRPL and WRPL can be used to measure production loss due to health-related and work environment-related problems. These results may have implications for advancing methods of assessing production loss, which represents an important cost to employers.

Design, synthesis and initial characterisation of a radiolabelled [(18)F]pyrimidoindolone probe for detecting activated caspase-3/7.

Evasion of apoptosis is one of the six initially proposed hallmarks of cancer, and as such, a method to detect apoptosis in a tumour would be of considerable interest in both clinical trials of new cancer therapeutics, as well as for routine patient management. Activation of caspase-3/7 is a key biomarker of cellular apoptosis. Herein we describe the design, synthesis and initial characterisation of the first pyrimidoindolone compound for detection of caspase-3/7 activation using positron emission tomography.

Parametric imaging of ¹8F-fluoro-3-deoxy-3-L-fluorothymidine PET data to investigate tumour heterogeneity.

PURPOSE: [(18)F]Fluoro-3'-deoxy-3'-L-fluorothymidine ([(18)F]FLT) is a tissue proliferation marker which has been widely validated as a tumour-specific imaging tracer for PET. [(18)F]FLT uptake in breast cancer is generally quantified at the region level or through first-order statistical descriptors (mean or maximum value), approaches that ignore the known complexity and heterogeneity of cancer tissues. Our aims were: (1) to validate a robust and reproducible voxel-wise approach to the quantification of [(18)F]FLT PET data in breast cancer patients, and (2) to exploit the entire distribution of the [(18)F]FLT retention estimates and their variability in the tumour region for the prediction of early treatment response. METHODS: The dataset was derived from 15 patients with stage II-IV breast cancer, scanned twice before chemotherapy and once 1 week after therapy. Using RECIST criteria (after 60 days) nine patients were categorized as responders or nonresponders to treatment. Kinetic modelling (compartmental modelling, Patlak analysis and spectral analysis with iterative filter), tissue-to-plasma ratio and standardized uptake value were applied at the voxel level. Test-retest estimates were used to assess reproducibility and reliability of the [(18)F]FLT uptake values before and after therapy for responder/nonresponder prediction. RESULTS: All the methods provided a measure of [(18)F]FLT uptake that was reliable and reproducible with ICC >0.94. Moreover, a very strong correlation was found among the methods (R (2) > 0.81). All the methods provided a limited number of outliers (<20 % in tumour), with the exception of compartmental modelling (>25 %) which was therefore excluded from the prediction analysis. Differences between before and after therapy in mean voxel-wise uptake in tumour did not allow a complete responder/nonresponder classification. In contrast, considering the full estimate distributions within the tumour (changes in median and mode between before and after therapy) improved therapy response for all the analysed methods. CONCLUSION: We showed that kinetic modelling (Patlak and spectral analysis with iterative filter) applied voxel-wise allows appropriate [(18)F]FLT uptake estimation in breast cancer with good reproducibility. Notably, this study indicated that a more comprehensive statistical investigation could improve tumour characterization and prediction of treatment response.

A novel small molecule hydroxamate preferentially inhibits HDAC6 activity and tumour growth.

BACKGROUND: This study investigates whether a histone deacetylase subtype 6 (HDAC6) inhibitor could be used in the treatment of solid tumours. METHODS: We evaluated the effect of a novel inhibitor, C1A, on HDAC6 biochemical activity and cell growth. We further examined potential of early noninvasive imaging of cell proliferation by [(18)F]fluorothymidine positron emission tomography ([(18)F]FLT-PET) to detect therapy response. RESULTS: C1A induced sustained acetylation of HDAC6 substrates, α-tubulin and HSP90, compared with current clinically approved HDAC inhibitor SAHA. C1A induced apoptosis and inhibited proliferation of a panel of human tumour cell lines from different origins in the low micromolar range. Systemic administration of the drug inhibited the growth of colon tumours in vivo by 78%. The drug showed restricted activity on gene expression with <0.065% of genes modulated during 24 h of treatment. C1A treatment reduced tumour [(18)F]FLT uptake by 1.7-fold at 48 h, suggesting that molecular imaging could provide value in future studies of this compound. CONCLUSION: C1A preferentially inhibits HDAC6 and modulates HDAC6 downstream targets leading to growth inhibition of a diverse set of cancer cell lines. This property together with the favourable pharmacokinetics and efficacy in vivo makes it a candidate for further pre-clinical and clinical development.

Development of a cyclin-dependent kinase inhibitor devoid of ABC transporter-dependent drug resistance.

BACKGROUND: Cyclin-dependent kinases (CDKs) control cell cycle progression, RNA transcription and apoptosis, making them attractive targets for anticancer drug development. Unfortunately, CDK inhibitors developed to date have demonstrated variable efficacy. METHODS: We generated drug-resistant cells by continuous low-dose exposure to a model pyrazolo[1,5-a]pyrimidine CDK inhibitor and investigated potential structural alterations for optimal efficacy. RESULTS: We identified induction of the ATP-binding cassette (ABC) transporters, ABCB1 and ABCG2, in resistant cells. Assessment of features involved in the ABC transporter substrate specificity from a compound library revealed high polar surface area (>100 Å(2)) as a key determinant of transporter interaction. We developed ICEC-0782 that preferentially inhibited CDK2, CDK7 and CDK9 in the nanomolar range. The compound inhibited phosphorylation of CDK substrates and downregulated the short-lived proteins, Mcl-1 and cyclin D1. ICEC-0782 induced G2/M arrest and apoptosis. The permeability and cytotoxicity of ICEC-0782 were unaffected by ABC transporter expression. Following daily oral dosing, the compound inhibited growth of human colon HCT-116 and human breast MCF7 tumour xenografts in vivo by 84% and 94%, respectively. CONCLUSION: We identified a promising pyrazolo[1,5-a]pyrimidine compound devoid of ABC transporter interaction, highly suitable for further preclinical and clinical evaluation for the treatment of cancer.

An open-label study of lapatinib in women with HER-2-negative early breast cancer: the lapatinib pre-surgical study (LPS study).

BACKGROUND: This phase II, open-label, multicentre study aimed to evaluate changes in cell proliferation and biomarkers, as well as efficacy of lapatinib in treatment-naïve patients with HER-2-negative primary breast cancer. PATIENTS AND METHODS: Patients received 1500 mg lapatinib for 28-42 days before surgery with repeat biopsies and measurements. The primary end point was inhibition of cell proliferation measured by Ki67; the secondary end points included clinical response, adverse events and changes in FOXO3a, FOXM1, p-AKT and HER-3. RESULTS: Overall, there was no significant reduction in Ki67 with treatment (assessment carried out in 28 of 31 subjects enrolled). However, four patients (14%) showed a reduction in Ki67 ≥50%. Four of 25 patients (16%) had a partial response to treatment judged by sequential ultrasound measurements. Response, in terms of either Ki67 or ultrasound, did not relate to changes in any biomarker assessed at baseline, including the estrogen receptor (ER) and epidermal growth factor receptor (EGFR). However, all four clinical responders were HER-3 positive, as were three of four Ki67 responders. CONCLUSIONS: Overall, a pre-surgical course of lapatinib monotherapy had little effect on this group of patients; however, in subsets of patients, especially those with HER-3-positive tumors, we observed either reduction in proliferation (Ki67) or tumor size; EGFR/ER status had no impact.

Synthesis and evaluation of 3'-[18F]fluorothymidine-5'-squaryl as a bioisostere of 3'-[18F]fluorothymidine-5'-monophosphate.

The squaryl moiety has emerged as an important phosphate bioisostere with reportedly greater cell permeability. It has been used in the synthesis of several therapeutic drug molecules including nucleoside and nucleotide analogues but is yet to be evaluated in the context of positron emission tomography (PET) imaging. We have designed, synthesised and evaluated 3'-[18F]fluorothymidine-5'-squaryl ([18F]SqFLT) as a bioisostere to 3'-[18F]fluorothymidine-5'-monophosphate ([18F]FLTMP) for imaging thymidylate kinase (TMPK) activity. The overall radiochemical yield (RCY) was 6.7 ± 2.5% and radiochemical purity (RCP) was >90%. Biological evaluation in vitro showed low tracer uptake (<0.3% ID mg-1) but significantly discriminated between wildtype HCT116 and CRISPR/Cas9 generated TMPK knockdown HCT116shTMPK-. Evaluation of [18F]SqFLT in HCT116 and HCT116shTMPK- xenograft mouse models showed statistically significant differences in tumour uptake, but lacked an effective tissue retention mechanism, making the radiotracer in its current form unsuitable for PET imaging of proliferation.

Guidelines for the welfare and use of animals in cancer research.

Animal experiments remain essential to understand the fundamental mechanisms underpinning malignancy and to discover improved methods to prevent, diagnose and treat cancer. Excellent standards of animal care are fully consistent with the conduct of high quality cancer research. Here we provide updated guidelines on the welfare and use of animals in cancer research. All experiments should incorporate the 3Rs: replacement, reduction and refinement. Focusing on animal welfare, we present recommendations on all aspects of cancer research, including: study design, statistics and pilot studies; choice of tumour models (e.g., genetically engineered, orthotopic and metastatic); therapy (including drugs and radiation); imaging (covering techniques, anaesthesia and restraint); humane endpoints (including tumour burden and site); and publication of best practice.

Radio- and nano-chemistry of aqueous Ga(iii) ions anchored onto graphene oxide-modified complexes.

The gallium-68 radiolabelling of new functional graphene oxide composites is reported herein along with kinetic stability investigations of the radio-nanohybrids under different environments and insights into their surface characteristics by SEM and XPS. The present work highlights the potential of graphene oxides as nanocarriers for small molecules such as bis(thiosemicarbazonato) complexes to act as multifunctional platforms for rapid and effective radioimaging agent incorporation.

Concurrent occurrence of a wandering spleen, organoaxial gastric volvulus, pancreatic volvulus, and cholestasis - A rare cause of an acute abdomen.

The concurrence of wandering spleen, organoaxial gastric volvulus, and pancreatic volvulus is very rare. They have been associated with symptoms such as severe abdominal pain, abdominal distention, and vomiting. However, the diagnosis remains complicated and any delay can result in ischemia and necrosis of the organs involved. In this case presentation, we present a unique case involving a 14-year-old girl who presented initially with acute abdominal pain. Assessment with enhanced computed tomography scan led to the diagnosis of wandering spleen, organoaxial gastric volvulus, and pancreatic volvulus, in addition to cholestasis, making it the first study to report on the simultaneous occurrence of this triad and cholestasis.

Plasma pharmacokinetic evaluation of cytotoxic agents radiolabelled with positron emitting radioisotopes.

PURPOSE: This study aimed to evaluate the utility of plasma pharmacokinetic analyses of anti-cancer agents from data obtained during positron emission tomography (PET) oncology studies of radiolabelled anti-cancer agents. PATIENTS AND METHODS: Thirteen patients were administered fluorine-18 radiolabelled 5-FU ([(18)F]5-FU) admixed with 5-FU, corresponding to a total 5-FU dose of 380-407 mg/m2 (eight patients) and 1 mg/m2 (five patients). Nine patients received 2.2-19.2 microg/m2 of carbon-11 radiolabelled N-[2-(dimethylamino)ethyl]acridine-4-carboxamide ([11C]DACA) at 1/1,000th of phase I dose, as part of phase 0 microdosing study. Radioactivity of parent drug obtained from arterial blood samples, the injected activity of the radiolabelled drug, and the total dose of injected drug were used to obtain plasma drug concentrations. Plasma pharmacokinetic parameters were estimated using model-dependent and model-independent methods. RESULTS: 5-FU plasma concentrations at therapeutic doses were above the Km and a single compartment kinetic model was best used to fit the kinetics, with a mean half-life of 8.6 min. Clearance and volumes of distribution (Vd) obtained using both model-dependent and model-independent methods were similar. Mean (SE) clearance was 1,421(144), ml min(-1) and 1,319 (119) ml min(-1) and the mean (SE) Vd was 17.3 (1.8) l and 16.3 (1.9) l by the model-independent method and model-dependent methods, respectively. In contrast, with 1 mg/m2, plasma concentrations of 5-FU were less than the Km and a two-compartment model was used to best fit the kinetics, with the mean 5-FU half-life of 6.5 min. The mean (SE) clearances obtained by the model-independent method and model-dependent methods were 3,089 (314) ml min(-1) and 2,225 (200) ml min(-1), respectively and the mean (SE) Vd were 27.9 (7.0) l and 2.3 (0.4) l, by the model independent and dependent methods, respectively. Extrapolation of AUC0-Clast to AUC0-infinity was less than 3% in both these cohort of patients. A two-compartment model with a mean half-life of 42.1 min was used to best fit the kinetics of DACA; considerable extrapolation (mean 26%) was required to obtain AUC0-infinity from AUC0-Clast. Mean (SE) clearance of DACA was 1,920 (269) ml min(-1), with the model-independent method and 1,627 (287) ml min(-1) with the model-dependent method. Similarly, Vd [mean (SE)] of DACA with the model-independent and model-dependent methods were 118 (22) l and 50 (15) l, respectively. CONCLUSIONS: Pharmacokinetic parameters can be estimated with confidence from PET studies for agents given at therapeutic doses, whose half-lives are significantly less than the total sampling time during the scan. Tracer studies performed alone, wherein plasma levels below the Km are expected, may also provide valuable information on drug clearance for the entire range of linear kinetics. However, drugs with half-lives longer than the sampling duration are inappropriate for PET plasma pharmacokinetic evaluation.

Towards an MMP-2-activated molecular agent for cancer imaging.

Matrix metalloproteinases (MMPs) have been identified as biomarkers for cancer, offering prognostic potential; however, non-invasive detection protocols are currently lacking. Herein, we describe the synthesis of a DOTA-containing peptide sequence that can be radiolabelled easily with 68Gallium or can be incorporated with gadolinium for possible MRI applications with clear selectivity for MMP-2 over other members of the MMP family, giving MMP-2 selective cleavage of the labelled peptides.

Bilateral emphysematous pyelonephritis cured by antibiotics alone in a black African woman.

A 78-year-old black woman with a 10-year history of diabetes mellitus was admitted to the intensive care unit. Upon admission, she presented with chills, nausea, and left flank pain. The presence of hyperglycemia (fasting blood glucose, 19.7 mmol/L) and an altered consciousness required immediate treatment with insulin analog. Laboratory investigations and enhanced computed tomography scan led to the diagnosis of bilateral emphysematous pyelonephritis (EPN). The patient responded well to conservative treatment with antibiotics, and was finally discharged after 22 days when the computed tomography scan showed resolution of all the pockets of air. This case and associated literature review of 25 previously reported cases of bilateral EPN show the changing trend of EPN management from emergency nephrectomy toward conservative treatment with potent antibiotics and/or percutaneous drainage, and has been associated with higher survival rates compared to emergency nephrectomy.