Clinical significance of prostate (18)F-labelled fluorodeoxyglucose uptake on positron emission tomography/computed tomography: A five-year review

AIM: To determine the significance and need for investigation of incidental prostatic uptake in men undergoing (18)F-labelled fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) for other indications. METHODS: Hospital databases were searched over a 5-year period for patients undergoing both PET/CT and prostate magnetic resonance imaging (MRI). For the initial analysis, the prostate was divided into six sectors and suspicious or malignant sectors were identified using MRI and histopathology reports respectively. Maximum and mean (18)F-FDG standardised uptake values were measured in each sector by an investigator blinded to the MRI and histopathology findings. Two age-matched controls were selected per case. Results were analysed using a paired t-test and one-way ANOVA. For the second analysis, PET/CT reports were searched for prostatic uptake reported incidentally and these patients were followed up. RESULTS: Over a 5-year period, 15 patients underwent both PET/CT and MRI and had biopsy-proven prostate cancer. Malignant prostatic sectors had a trend to higher (18)F-FDG uptake than benign sectors, however this was neither clinically nor statistically significant (3.13 ± 0.58 vs 2.86 ± 0.68, P > 0.05). (18)F-FDG uptake showed no correlation with the presence or histopathological grade of tumour. (18)F-FDG uptake in cases with prostate cancer was comparable to that from age-matched controls. Forty-six (1.6%) of 2846 PET/CTs over a 5-year period reported incidental prostatic uptake. Of these, 18 (0.6%) were investigated by PSA, 9 (0.3%) were referred to urology, with 3 (0.1%) undergoing MRI and/or biopsy. No cases of prostate cancer were diagnosed in patients with incidental (18)F-FDG uptake in our institute over a 5-year period. CONCLUSION: (18)F-FDG uptake overlaps significantly between malignant and benign prostatic conditions. Subsequent patient management was not affected by the reporting of incidental focal prostatic uptake in this cohort

Experimental observation of the breaking and recombination of single Cooper pairs

We observe the real-time breaking of single Cooper pairs by monitoring the radio-frequency impedance of a superconducting double quantum dot. The Cooper pair breaking rate in the microscale islands of our device decreases as temperature is reduced, saturating at 2 kHz for temperatures beneath 100 mK. In addition, we measure in real-time the quasiparticle recombination into Cooper pairs. Analysis of the recombination rates shows that, in contrast to bulk lms, a multi-stage recombination pathway is followed.A.J.F. would like to acknowledge the Hitachi Research fellowship, support from Hitachi Cambridge Laboratory and support from the EPSRC grant EP/H016872/1. B.W.L. is supported by a Royal Society University Research Fellowship. F.A.P. would like to thank the Leverhulme Trust for fi nancial support.This is the author accepted manuscript. The final version is available from APS via http://dx.doi.org/10.1103/PhysRevB.90.14050

The Prostate Health Index adds predictive value to multi-parametric MRI in detecting significant prostate cancers in a repeat biopsy population

Both multi-parametric MRI (mpMRI) and the Prostate Health Index (PHI) have shown promise in predicting a positive biopsy in men with suspected prostate cancer. Here we investigated the value of combining both tests in men requiring a repeat biopsy. PHI scores were measured in men undergoing re-biopsy with an mpMRI image-guided transperineal approach (n = 279, 94 with negative mpMRIs). The PHI was assessed for ability to add value to mpMRI in predicting all or only significant cancers (Gleason ≥7). In this study adding PHI to mpMRI improved overall and significant cancer prediction (AUC 0.71 and 0.75) compared to mpMRI + PSA alone (AUC 0.64 and 0.69 respectively). At a threshold of ≥35, PHI + mpMRI demonstrated a NPV of 0.97 for excluding significant tumours. In mpMRI negative men, the PHI again improved prediction of significant cancers; AUC 0.76 vs 0.63 (mpMRI + PSA). Using a PHI≥35, only 1/21 significant cancers was missed and 31/73 (42%) men potentially spared a re-biopsy (NPV of 0.97, sensitivity 0.95). Decision curve analysis demonstrated clinically relevant utility of the PHI across threshold probabilities of 5-30%. In summary, the PHI adds predictive performance to image-guided detection of clinically significant cancers and has particular value in determining re-biopsy need in men with a negative mpMRI

The longitudinal effect of ejaculation on seminal vesicle fluid volume and whole-prostate ADC as measured on prostate MRI.

OBJECTIVE: To prospectively investigate the longitudinal effect of ejaculatory abstinence on MRI-measured seminal vesicle (SV) volume and whole-prostate ADC over consecutive days. METHODS: 15 healthy male volunteers (mean 35.9 years, range 27-53) underwent 3-T MRI at baseline and 1, 2 and 3 days post-ejaculation. Prostate and SV volumes were derived by volume segmentation and whole-gland apparent diffusion coefficient (ADC) values calculated. A mixed-effects linear regression compared ADC values and prostate/seminal vesicle volumes in each volunteer between studies in a pairwise manner. RESULTS: All subjects completed the four MRIs. Mean prostate volume was 22.45 cm³ (range 13.04-31.21 cm³), with no change between the four studies (p = 0.89-0.99). 13/15 subjects showed SV volume reduction from baseline to day 1, with group-mean decreasing from 6.45 to 4.80 cm³ (-25.6%, p < 0.001), and a significant reduction from baseline to day 2 (-18.1%, p = 0.002). There was a significant volume increase from both day 1 (+21.3%, p = 0.006) and day 2 (+10.2%, p = 0.022) to day 3 post-ejaculation. There was a significant reduction in ADC from 1.105 at baseline to 1.056 × 10¯³ mm²/s at day 1 (mean -4.3%, p = 0.009). CONCLUSION: The longitudinal effect of ejaculation on SV volume was demonstrated. Significant reductions in SV volume and whole-gland ADC were observed post-ejaculation, supporting a 3-day period of abstinence before prostate MRI. KEY POINTS: • Seminal vesicle volume significantly reduced 24 h post-ejaculation remaining reduced at day 2 • Seminal vesicle fluid volume significantly increased from day 1 to day 3 post-ejaculation • There was a significant reduction in whole-gland prostate ADC values day 1 post-ejaculation • 3-day abstinence from ejaculation is required to ensure maximal seminal vesicle distension.The authors acknowledge grant support from the Royal College of Radiologists UK and research support from Cancer Research UK, National Institute of Health Research Cambridge Biomedical Research Centre, Cancer Research UK and the Engineering and Physical Sciences Research Council Imaging Centre in Cambridge and Manchester and the Cambridge Experimental Cancer Medicine Centre

Removing rician bias in diffusional kurtosis of the prostate using real-data reconstruction.

Purpose To compare prostate diffusional kurtosis imaging (DKI) metrics generated using phase-corrected real data with those generated using magnitude data with and without noise compensation (NC).Methods Diffusion-weighted images were acquired at 3T in 16 prostate cancer patients, measuring 6 b-values (0-1500 s/mm2 ), each acquired with 6 signal averages along 3 diffusion directions, with noise-only images acquired to allow NC. In addition to conventional magnitude averaging, phase-corrected real data were averaged in an attempt to reduce rician noise-bias, with a range of phase-correction low-pass filter (LPF) sizes (8-128 pixels) tested. Each method was also tested using simulations. Pixelwise maps of apparent diffusion (D) and apparent kurtosis (K) were calculated for magnitude data with and without NC and phase-corrected real data. Average values were compared in tumor, normal transition zone (NTZ), and normal peripheral zone (NPZ).Results Simulations indicated LPF size can strongly affect K metrics, where 64-pixel LPFs produced accurate metrics. Relative to metrics estimated from magnitude data without NC, median NC K were lower (P < 0.0001) by 6/11/8% in tumor/NPZ/NTZ, 64-LPF real-data K were lower (P < 0.0001) by 4/10/7%, respectively.Conclusion Compared with magnitude data with NC, phase-corrected real data can produce similar K, although the choice of phase-correction LPF should be chosen carefully

Plasmodium knowlesi Genome Sequences from Clinical Isolates Reveal Extensive Genomic Dimorphism.

Plasmodium knowlesi is a newly described zoonosis that causes malaria in the human population that can be severe and fatal. The study of P. knowlesi parasites from human clinical isolates is relatively new and, in order to obtain maximum information from patient sample collections, we explored the possibility of generating P. knowlesi genome sequences from archived clinical isolates. Our patient sample collection consisted of frozen whole blood samples that contained excessive human DNA contamination and, in that form, were not suitable for parasite genome sequencing. We developed a method to reduce the amount of human DNA in the thawed blood samples in preparation for high throughput parasite genome sequencing using Illumina HiSeq and MiSeq sequencing platforms. Seven of fifteen samples processed had sufficiently pure P. knowlesi DNA for whole genome sequencing. The reads were mapped to the P. knowlesi H strain reference genome and an average mapping of 90% was obtained. Genes with low coverage were removed leaving 4623 genes for subsequent analyses. Previously we identified a DNA sequence dimorphism on a small fragment of the P. knowlesi normocyte binding protein xa gene on chromosome 14. We used the genome data to assemble full-length Pknbpxa sequences and discovered that the dimorphism extended along the gene. An in-house algorithm was developed to detect SNP sites co-associating with the dimorphism. More than half of the P. knowlesi genome was dimorphic, involving genes on all chromosomes and suggesting that two distinct types of P. knowlesi infect the human population in Sarawak, Malaysian Borneo. We use P. knowlesi clinical samples to demonstrate that Plasmodium DNA from archived patient samples can produce high quality genome data. We show that analyses, of even small numbers of difficult clinical malaria isolates, can generate comprehensive genomic information that will improve our understanding of malaria parasite diversity and pathobiology

Group art therapy as an adjunctive treatment for people with schizophrenia: a randomised controlled trial (MATISSE).

OBJECTIVE: To examine the clinical effectiveness and cost-effectiveness of referral to group art therapy plus standard care, compared with referral to an activity group plus standard care and standard care alone, among people with schizophrenia. DESIGN: A three-arm, parallel group, single-blind, pragmatic, randomised controlled trial. Participants were randomised via an independent and remote telephone randomisation service using permuted blocks, stratified by study centre. SETTING: Study participants were recruited from secondary care mental health and social services in four UK centres. PARTICIPANTS: Potential participants were aged 18 years or over, had a clinical diagnosis of schizophrenia, confirmed by an examination of case notes, and provided written informed consent. We excluded those who were unable to speak sufficient English to complete the baseline assessment, those with severe cognitive impairment and those already receiving arts therapy. INTERVENTIONS: Group art therapy was delivered by registered art therapists according to nationally agreed standards. Groups had up to eight members, lasted for 90 minutes and ran for 12 months. Members were given access to a range of art materials and encouraged to use these to express themselves freely. Activity groups were designed to control for the non-specific effects of group art therapy. Group facilitators offered various activities and encouraged participants to collectively select those they wanted to pursue. Standard care involved follow-up from secondary care mental health services and the option of referral to other services, except arts therapies, as required. MAIN OUTCOME MEASURES: Our co-primary outcomes were global functioning (measured using the Global Assessment of Functioning Scale - GAF) and mental health symptoms (measured using the Positive and Negative Syndrome Scale - PANSS) at 24 months. The main secondary outcomes were level of group attendance, social functioning, well-being, health-related quality of life, service utilisation and other costs measured 12 and 24 months after randomisation. RESULTS: Four hundred and seventeen people were recruited, of whom 355 (85%) were followed up at 2 years. Eighty-six (61%) of those randomised to art therapy and 73 (52%) of those randomised to activity groups attended at least one group. No differences in primary outcomes were found between the three study arms. The adjusted mean difference between art therapy and standard care at 24 months was -0.9 [95% confidence interval (CI) -3.8 to 2.1] on the GAF Scale and 0.7 (95% CI -3.1 to 4.6) on the PANSS Scale. Differences in secondary outcomes were not found, except that those referred to an activity group had fewer positive symptoms of schizophrenia at 24 months than those randomised to art therapy. Secondary analysis indicated that attendance at art therapy groups was not associated with improvements in global functioning or mental health. Although the total cost of the art therapy group was lower than the cost of the two comparison groups, referral to group art therapy did not appear to provide a cost-effective use of resources. CONCLUSIONS: Referring people with established schizophrenia to group art therapy as delivered in this randomised trial does not appear to improve global functioning or mental health of patients or provide a more cost-effective use of resources than standard care alone. TRIAL REGISTRATION: Current Controlled Trials ISRCTN 46150447. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 16, No. 8. See the HTA programme website for further project information

Phylogeography of Japanese encephalitis virus:genotype is associated with climate

The circulation of vector-borne zoonotic viruses is largely determined by the overlap in the geographical distributions of virus-competent vectors and reservoir hosts. What is less clear are the factors influencing the distribution of virus-specific lineages. Japanese encephalitis virus (JEV) is the most important etiologic agent of epidemic encephalitis worldwide, and is primarily maintained between vertebrate reservoir hosts (avian and swine) and culicine mosquitoes. There are five genotypes of JEV: GI-V. In recent years, GI has displaced GIII as the dominant JEV genotype and GV has re-emerged after almost 60 years of undetected virus circulation. JEV is found throughout most of Asia, extending from maritime Siberia in the north to Australia in the south, and as far as Pakistan to the west and Saipan to the east. Transmission of JEV in temperate zones is epidemic with the majority of cases occurring in summer months, while transmission in tropical zones is endemic and occurs year-round at lower rates. To test the hypothesis that viruses circulating in these two geographical zones are genetically distinct, we applied Bayesian phylogeographic, categorical data analysis and phylogeny-trait association test techniques to the largest JEV dataset compiled to date, representing the envelope (E) gene of 487 isolates collected from 12 countries over 75 years. We demonstrated that GIII and the recently emerged GI-b are temperate genotypes likely maintained year-round in northern latitudes, while GI-a and GII are tropical genotypes likely maintained primarily through mosquito-avian and mosquito-swine transmission cycles. This study represents a new paradigm directly linking viral molecular evolution and climate

Management of anterior cruciate ligament rupture in patients aged 40 years and older

The aim of anterior cruciate ligament (ACL) reconstruction is essentially to restore functional stability of the knee and to allow patients to return to their desired work and activities. While in the young and active population, surgery is often the best therapeutic option after an ACL tear, ACL reconstruction in middle-aged people is rather more controversial due to concerns about a higher complication rate. The purpose of our article is to establish, through a systematic review of the literature, useful decision-making criteria for the management of anterior cruciate ligament rupture in patients aged 40 years and older, guiding surgeons to the most appropriate therapeutic approach. Various reports have shown excellent results of ACL reconstruction in patients over the age of 40 in terms of subjective satisfaction, return to previous activity level, and reduced complication and failure rates. Some even document excellent outcomes in subjects of 50 years and older. Although there are limited high-level studies, data reported in the literature suggest that ACL reconstruction can be successful in appropriately selected, motivated older patients with symptomatic knee instability who want to return to participating in highly demanding sport and recreational activities. Deciding factors are based on occupation, sex, activity level of the subject, amount of time spent performing such highly demanding activities, and presence of associated knee lesions. Physiological age and activity level are more important than chronological age as deciding factors when considering ACL reconstruction