Reasons for Discordance between 68Ga-PSMA-PET and Magnetic Resonance Imaging in Men with Metastatic Prostate Cancer.

BACKGROUND: PSMA PET has emerged as a "gold standard" imaging modality for assessing prostate cancer metastases. However, it is not universally available, and this limits its impact. In contrast, whole-body MRI is much more widely available but misses more lesions. This study aims to improve the interpretation of whole-body MRI by comparing false negative scans retrospectively to PSMA PET. METHODS: This study was a retrospective sub-analysis of a prospectively collected database of patients who participated in a clinical trial of PSMA PET/MRI comparing PSMA PET and whole-body MRI from 2018-2021. Subjects whose separately read PSMA PET and MRI diagnostic reports showed discrepancies ("false negative" MRI cases) were selected for sub-analysis. The cases were reviewed by the same attending radiologist who originally read the scans. The radiologist noted specific features on MRI indicating metastatic disease that were initially missed. RESULTS: Of 263 cases, 38 (14%) met the inclusion criteria and were reviewed. Six classes of mpMRI false negatives were identified: anatomically normal (18, 47%), atypical MRI appearance (6, 16%), mischaracterization (1, 3%), undercall (6, 16%), obscured (4, 11%), and no abnormality on MRI (3, 8%). Considering that the atypical and undercalled cases could have been adjusted in retrospect, and that 4 additional cases had positive lesions to the same extent and 11 further cases had disease confined to the pelvis, only 11 (4%) of the original 263 would have had disease outside of a conventional radiation treatment plan. CONCLUSION: Notably, almost 50% of the cases, including most lymph node metastases, were anatomically normal using standard criteria. This suggests that current anatomic criteria for evaluating prostate cancer lymph node metastases are not ideal, and there is a need for improved criteria. In addition, 32% of cases involved some element of human interpretive error, and, therefore, improving reader training may lead to more accurate results.

Chronic inflammation decreases arcuate kisspeptin expression in male sheep.

Lipopolysaccharide (LPS) from Gram-negative bacteria induces an immune response and impairs reproduction through suppression of gonadotropin releasing hormone (GnRH), subsequently luteinizing hormone (LH) secretion. While there is evidence that acute inflammation inhibits kisspeptin, little is known about the impact of chronic inflammation on this key reproductive neuropeptide in livestock species. Thus, we sought to examine a central mechanism whereby LPS suppresses LH secretion in sheep. Twenty wethers were randomly assigned to one of five treatment groups: control (CON; n=4), single acute IV LPS dose (SAD; n=4), daily acute IV LPS dose (DAD; n=4), daily increasing IV LPS dose (DID; n=4), and chronic subcutaneous LPS dose (CSD; n=4). On Days 1 and 7, blood samples were collected every 12 minutes for 360 minutes using jugular venipuncture. Following blood collection on Day 7, all animals were euthanized, brain tissue was perfused with 4% paraformaldehyde, and hypothalamic blocks were removed and processed for immunohistochemistry. On Day 1, LH pulse frequency was significantly lower (p=0.02) in SAD (0.25 ± 0.1 pulses/hour), DAD (0.25 ± 0.1 pulses/hour), DID (0.35 ± 0.1 pulses/hour), and CSD (0.40 ± 0.1 pulses/hour) compared to CON (0.70 ±0.1 pulses/hour). On Day 7, only DID animals (0.35 ± 0.1 pulses/hour) had significantly lower (p=0.049) LH pulse frequency compared to controls (0.85 ± 0.1 pulse/hour). Furthermore, only DID animals (33.3 ± 10.9 cells/section/animal) had significantly fewer (p=0.001) kisspeptin-immunopositive cells compared to controls (82.6 ± 13.6 cells/section/animal). Taken together, we suggest that daily increasing doses of LPS is a powerful inhibitor of kisspeptin neurons in young male sheep and a physiologically relevant model to examine the impact of chronic inflammation on the reproductive axis in livestock.

MRI-Ultrasound Fused Approach for Prostate Biopsy-How It Is Performed.

The use of MRI-ultrasound image fusion targeted biopsy of the prostate in the face of an elevated serum PSA is now recommended by multiple societies, and results in improved detection of clinically significant cancer and, potentially, decreased detection of indolent disease. This combines the excellent sensitivity of MRI for clinically significant prostate cancer and the real-time biopsy guidance and confirmation of ultrasound. Both transperineal and transrectal approaches can be implemented using cognitive fusion, mechanical fusion with an articulated arm and electromagnetic registration, or pure software registration. The performance has been shown comparable to in-bore MRI biopsy performance. However, a number of factors influence the performance of this technique, including the quality and interpretation of the MRI, the approach used for biopsy, and experience of the practitioner, with most studies showing comparable performance of MRI-ultrasound fusion to in-bore targeted biopsy. Future improvements including artificial intelligence promise to refine the performance of all approaches.

Outcomes of percutaneous vertebroplasty in multiple myeloma: a tertiary neurosciences experience with long-term follow-up.

Background: Multiple myeloma is diagnosed in 5,800 people in the United Kingdom (UK) each year with up to 64% having vertebral compression fractures at the time of diagnosis. Painful vertebral compression fractures can be of significant detriment to patients' quality of life. Percutaneous vertebroplasty aims to provide long-term pain relief and stabilize fractured vertebrae. Methods and materials: Data was collected from all cases of percutaneous vertebroplasty performed on patients with multiple myeloma from November 2017 to January 2019. Pain scores were measured using the Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) pre-procedure, 2 months post procedure and 4 years post-procedure. Procedure related complications and analgesia use were also documented. Results: 22 patients were included with a total of 119 vertebrae treated. Patients reported a significant improvement in overall pain score with a median pre-procedure VAS of 8 and a median post-procedure VAS of 3.5 (p<0.0001). There was a median pre-procedure ODI score of 60% and a median post-procedure ODI score of 36% (p<0000.1). There was improvement across all ODI domains and a 77% reduction in analgesic requirement. There were small cement leaks into paravertebral veins or endplates at 15 levels (12%) which were asymptomatic. There were 8 responders to the long-term follow-up questionnaire at 4 years. This demonstrated an overall stable degree of pain relief in responders with a median VAS of 3.5 and median ODI of 30%. Conclusion: At this center, vertebroplasty has been shown to reduce both VAS and ODI pain scores and reduce analgesia requirements in patients with VCFs secondary to multiple myeloma with long lasting relief at 4 years post-procedure.

Genetic parameters and genome-wide association studies for mozzarella and milk production traits, lactation length, and lactation persistency in Murrah buffaloes.

Genetic and genomic analyses of longitudinal traits related to milk production efficiency are paramount for optimizing water buffaloes breeding schemes. Therefore, this study aimed to (1) compare single-trait random regression models under a single-step genomic BLUP setting based on alternative covariance functions (i.e., Wood, Wilmink, and Ali and Schaeffer) to describe milk (MY), fat (FY), protein (PY), and mozzarella (MZY) yields, fat-to-protein ratio (FPR), somatic cell score (SCS), lactation length (LL), and lactation persistency (LP) in Murrah dairy buffaloes (Bubalus bubalis); (2) combine the best functions for each trait under a multiple-trait framework; (3) estimate time-dependent SNP effects for all the studied longitudinal traits; and (4) identify the most likely candidate genes associated with the traits. A total of 323,140 test-day records from the first lactation of 4,588 Murrah buffaloes were made available for the study. The model included the average curve of the population nested within herd-year-season of calving, systematic effects of number of milkings per day, and age at first calving as linear and quadratic covariates, and additive genetic, permanent environment, and residual as random effects. The Wood model had the best goodness of fit based on the deviance information criterion and posterior model probabilities for all traits. Moderate heritabilities were estimated over time for most traits (0.30 ± 0.02 for MY; 0.26 ± 0.03 for FY; 0.45 ± 0.04 for PY; 0.28 ± 0.05 for MZY; 0.13 ± 0.02 for FPR; and 0.15 ± 0.03 for SCS). The heritability estimates for LP ranged from 0.38 ± 0.02 to 0.65 ± 0.03 depending on the trait definition used. Similarly, heritabilities estimated for LL ranged from 0.10 ± 0.01 to 0.14 ± 0.03. The genetic correlation estimates across days in milk (DIM) for all traits ranged from -0.06 (186-215 DIM for MY-SCS) to 0.78 (66-95 DIM for PY-MZY). The SNP effects calculated for the random regression model coefficients were used to estimate the SNP effects throughout the lactation curve (from 5 to 305 d). Numerous relevant genomic regions and candidate genes were identified for all traits, confirming their polygenic nature. The candidate genes identified contribute to a better understanding of the genetic background of milk-related traits in Murrah buffaloes and reinforce the value of incorporating genomic information in their breeding programs.

Management of Patients With a Negative Multiparametric Prostate MRI Examination: AJR Expert Panel Narrative Review.

Multiparametric prostate MRI (mpMRI) aids risk stratification of patients with elevated PSA levels. While most clinically significant prostate cancers are detected by mpMRI, insignificant cancers are less evident. Thus, multiple international prostate cancer guidelines now endorse routine use of prostate MRI as a secondary screening test before prostate biopsy. Nonetheless, management of patients with negative mpMRI results (defined as PI-RADS category 1 or 2) remains unclear. This AJR Expert Panel Narrative Review summarizes the available literature on patients with an elevated screening PSA level and a negative prostate mpMRI, and provides guidance for these patients' management. Systematic biopsy should not be routinely performed after a negative mpMRI in patients at average risk but should be considered in patients at high risk. In patients who undergo PSA screening rather than systematic biopsy after negative mpMRI, clear triggers should be established for when to perform a repeat MRI. Patients with negative MRI followed by negative biopsy should follow their healthcare practitioners' preferred guidelines concerning subsequent PSA screening for the patient's risk level. Insufficient high-level data exist to support routine use of adjunctive serum or urine biomarkers, artificial intelligence, or PSMA PET to determine the need for prostate biopsy after negative mpMRI.

Partial-gland Cryoablation Outcomes for Localized Prostate Cancer in Patients with Magnetic Resonance Imaging (MRI)-visible and MRI-invisible Lesions.

Background: Expert consensus recommends treatment of magnetic resonance imaging (MRI)-visible prostate cancer (PCa). Outcomes of partial-gland ablation (PGA) for MRI-invisible PCa remain unknown. Objective: To compare recurrence-free survival, adverse events, and health-related quality of life (HRQoL) outcomes following cryoablation of MRI-visible vs invisible PCa. Design setting and participants: We analyzed data for 75 men who underwent cryoablation therapy between January 2017 and January 2022. PCa identified on MRI-targeted and/or adjacent systematic biopsy cores was defined as MRI-visible, whereas PCa identified on systematic biopsy beyond the targeted zone was defined as MRI-invisible. Outcome measurements and statistical analysis: The primary outcome was recurrence at 12 mo after PGA, defined as the presence of clinically significant PCa (grade group [GG] ≥2) on surveillance biopsy. Adverse events were captured using the Clavien-Dindo classification and HRQoL was captured using the Expanded Prostate Cancer Index-Clinical Practice (EPIC-CP) tool. Results and limitations: Of the 58 men treated for MRI-visible and 17 treated for MRI-invisible lesions, 51 (88%) and 16 (94%), respectively, had at least one surveillance biopsy performed. There were no statistically significant differences in age, race, body mass index, biopsy GG, prostate-specific antigen, prostate volume, or treatment extent between the MRI-visible and MRI-invisible groups. Median follow-up was 44 mo (interquartile range 17-54) and did not significantly differ between the groups. The recurrence rate at 12 mo did not significantly differ between the groups (MRI-visible 39%, MRI-invisible 19%; p = 0.2), and log-rank survival analysis demonstrated no significant difference in recurrence-free survival (p = 0.15). Adverse event rates did not significantly differ (MRI-visible 29%, MRI-invisible 53%; p = 0.092); no man in the MRI-visible group had a Clavien-Dindo grade ≥III complication, while one subject in the MRI-invisible group had a Clavien-Dindo grade III complication. Median EPIC-CP urinary and sexual function scores were similar for the two groups at baseline and at 12 mo after PGA. Study limitations include the retrospective design and small sample size. Conclusions: We observed similar cancer control, adverse event, and HRQoL outcomes for MRI-visible versus MRI-invisible PCa in the first comparison of partial-gland cryoablation. Longer follow-up and external validation of our findings are needed to inform patient selection for PGA for MRI-invisible PCa. Patient summary: Patients with prostate cancer lesions that are not visible on magnetic resonance imaging (MRI) scans who undergo partial gland ablation may have similar treatment outcomes compared to patients with cancer lesions that are visible on MRI.

The role of AI in prostate MRI quality and interpretation: Opportunities and challenges.

Prostate MRI plays an important role in imaging the prostate gland and surrounding tissues, particularly in the diagnosis and management of prostate cancer. With the widespread adoption of multiparametric magnetic resonance imaging in recent years, the concerns surrounding the variability of imaging quality have garnered increased attention. Several factors contribute to the inconsistency of image quality, such as acquisition parameters, scanner differences and interobserver variabilities. While efforts have been made to standardize image acquisition and interpretation via the development of systems, such as PI-RADS and PI-QUAL, the scoring systems still depend on the subjective experience and acumen of humans. Artificial intelligence (AI) has been increasingly used in many applications, including medical imaging, due to its ability to automate tasks and lower human error rates. These advantages have the potential to standardize the tasks of image interpretation and quality control of prostate MRI. Despite its potential, thorough validation is required before the implementation of AI in clinical practice. In this article, we explore the opportunities and challenges of AI, with a focus on the interpretation and quality of prostate MRI.

Applying the behaviour change wheel to assess the theoretical underpinning of a novel smartphone application to increase physical activity in adults with spinal cord injuries.

Background: People with spinal cord injuries (SCI) are physically inactive. Smartphone applications (or apps) may prove as one strategy to overcome this. This study examines the theoretical underpinning of a novel mHealth intervention that aims to improve physical activity in people with SCI, namely, the Accessercise smartphone app, using the behaviour change wheel (BCW). Methods: Accessercise was evaluated using the BCW in eight steps across the following three stages: (I) understanding the behaviour, (II) identifying intervention options, and (III) identifying content and implementation options. Results: Thirteen target behaviours were identified to improve physical activity and reduce sedentary behaviours in adults with SCI, including goal setting and monitoring, increasing self-confidence, interest and motivation for undertaking physical activity, improving the knowledge/awareness of available physical activity opportunities and resources, and reducing stigma and negative attitudes associated with physical activity. Accessercise incorporates the necessary components for adults with SCI to be physically and psychologically capable of undertaking physical activity, offering social and physical opportunities to reduce sedentary behaviours, and supports automatic and reflective motivation. Conclusions: This systematic approach of assessing the theoretical underpinning of Accessercise in the context of the BCW has revealed potential mechanisms of action for improving physical activity in adults with SCI. This serves as a blueprint to inform further intervention development, as well as high-quality effectiveness studies, namely, randomised controlled trials, assessing whether fitness apps can improve physical and psychological health outcomes in individuals with SCI.

Variability of Prostate MRI Charges Among U.S. Hospital-Based Facilities.

The Premier Healthcare Database was used to assess charge variation for prostate MRI examinations in U.S. hospitals from January 2010 to March 2020. In 552 facilities performing 37,073 examinations, the median charge per examination was $4419 with 26-fold variation between the lowest ($593) and highest ($15,150) median facility charges. In multilevel linear regression analysis, interfacility variation explained 63.9% of charge variation. Patients may be charged vastly different prices for prostate MRI depending on the facility.

Pulse Sequence Dependence of a Simple and Interpretable Deep Learning Method for Detection of Clinically Significant Prostate Cancer Using Multiparametric MRI.

RATIONALE AND OBJECTIVES: Multiparametric magnetic resonance imaging (mpMRI) is increasingly used for risk stratification and localization of prostate cancer (PCa). Thanks to the great success of deep learning models in computer vision, the potential application for early detection of PCa using mpMRI is imminent. MATERIALS AND METHODS: Deep learning analysis of the PROSTATEx dataset. RESULTS: In this study, we show a simple convolutional neural network (CNN) with mpMRI can achieve high performance for detection of clinically significant PCa (csPCa), depending on the pulse sequences used. The mpMRI model with T2-ADC-DWI achieved 0.90 AUC score in the held-out test set, not significantly better than the model using Ktrans instead of DWI (AUC 0.89). Interestingly, the model incorporating T2-ADC- Ktrans better estimates grade. We also describe a saliency "heat" map. Our results show that csPCa detection models with mpMRI may be leveraged to guide clinical management strategies. CONCLUSION: Convolutional neural networks incorporating multiple pulse sequences show high performance for detection of clinically-significant prostate cancer, and the model including dynamic contrast-enhanced information correlates best with grade.

Impacts of shared mobility on vehicle lifetimes and on the carbon footprint of electric vehicles.

Shared cars will likely have larger annual vehicle driving distances than individually owned cars. This may accelerate passenger car retirement. Here we develop a semi-empirical lifetime-driving intensity model using statistics on Swedish vehicle retirement. This semi-empirical model is integrated with a carbon footprint model, which considers future decarbonization pathways. In this work, we show that the carbon footprint depends on the cumulative driving distance, which depends on both driving intensity and calendar aging. Higher driving intensities generally result in lower carbon footprints due to increased cumulative driving distance over the vehicle's lifetime. Shared cars could decrease the carbon footprint by about 41% in 2050, if one shared vehicle replaces ten individually owned vehicles. However, potential empty travel by autonomous shared vehicles-the additional distance traveled to pick up passengers-may cause carbon footprints to increase. Hence, vehicle durability and empty travel should be considered when designing low-carbon car sharing systems.

If Electric Cars Are Good for Reducing Emissions, They Could Be Even Better with Electric Roads.

This research investigates carbon footprint impacts for full fleet electrification of Swedish passenger car travel in combination with different charging conditions, including electric road system (ERS) that enables dynamic on-road charging. The research applies a prospective life cycle analysis framework for estimating carbon footprints of vehicles, fuels, and infrastructure. The framework includes vehicle stock turnover modeling of fleet electrification and modeling of optimal battery capacity for different charging conditions based on Swedish real-world driving patterns. All new car sales are assumed to be electric after 2030 following phase-out policies for gasoline and diesel cars. Implementing ERS on selected high-traffic roads could yield significant avoided emissions in battery manufacturing compared to the additional emissions in ERS construction. ERS combined with stationary charging could enable additional reductions in the cumulative carbon footprint of about 12-24 million tons of CO2 over 30 years (2030-2060) compared to an electrified fleet only relying on stationary charging. The range depends on uncertainty in emission abatement in global manufacturing, where the lower is based on Paris Agreement compliance and the higher on current climate policies. A large share of the reduction could be achieved even if only a small share of the cars adopts the optimized battery capacities.

Paris Agreement requires substantial, broad, and sustained policy efforts beyond COVID-19 public stimulus packages.

It has been claimed that COVID-19 public stimulus packages could be sufficient to meet the short-term energy investment needs to leverage a shift toward a pathway consistent with the 1.5 °C target of the Paris Agreement. Here, we provide complementary perspectives to reiterate that substantial, broad, and sustained policy efforts beyond stimulus packages will be needed for achieving the Paris Agreement long-term targets. Low-carbon investments will need to scale up and persist over the next several decades following short-term stimulus packages. The required total energy investments in the real world can be larger than the currently available estimates from integrated assessment models (IAMs). Existing databases from IAMs are not sufficient for analyzing the effect of public spending on emission reduction. To inform what role COVID-19 stimulus packages and public investments may play for reaching the Paris Agreement targets, explicit modelling of such policies is required.

The (extended) achondroplasia foramen magnum score has good observer reliability.

BACKGROUND: Achondroplasia is the most common skeletal dysplasia. A significant complication is foramen magnum stenosis. When severe, compression of the spinal cord may result in sleep apnea, sudden respiratory arrest and death. To avoid complications, surgical decompression of the craniocervical junction is offered in at-risk cases. However, practice varies among centres. To standardize magnetic resonance (MR) reporting, the achondroplasia foramen magnum score was recently developed. The reliability of the score has not been assessed. OBJECTIVE: To assess the interobserver reliability of the achondroplasia foramen magnum score. MATERIALS AND METHODS: Base of skull imaging of children with achondroplasia under the care of Sheffield Children's Hospital was retrospectively and independently reviewed by four observers using the achondroplasia foramen magnum score. Two-way random-effects intraclass coefficient (ICC) was used to assess inter- and intra-observer reliability. RESULTS: Forty-nine eligible cases and five controls were included. Of these, 10 were scored normal, 17 had a median score of 1 (mild narrowing), 11 had a median score of 2 (effacement of cerebral spinal fluid), 10 had a score of 3 (compression of cord) and 6 had a median score of 4 (cord myelopathic change). Interobserver ICC was 0.72 (95% confidence interval = 0.62-0.81). Intra-observer ICC ranged from 0.60 to 0.86. Reasons for reader disagreement included flow void artefact, subtle T2 cord signal and myelopathic T2 cord change disproportionate to canal narrowing. CONCLUSION: The achondroplasia foramen magnum score has good interobserver reliability. Imaging features leading to interobserver disagreement have been identified. Further research is required to prospectively validate the score against clinical outcomes.