Reducing Temperature of Fused Deposition Modelling 3D Printing for Linalool Fast Dissolving Oral Films by Increasing Printer Nozzle Diameter.

Oral thrush and throat infections can occur in a wide range of patients. Treatments are available; however, resistance to drugs is a major problem for treating oral and throat infections. Three-dimensional printing (3DP) of fast dissolving oral films (FDFs) of linalool oil may provide an alternative solution. Linalool oil FDFs were printed by fused deposition modelling across 1-18% w/w linalool content range with nozzle diameters of 0.4 or 1 mm at the temperature range of 150°C-185°C. The FDFs were evaluated for physicochemical and mechanical properties. Increasing the printer nozzle diameter to 1 mm allowed reducing the printing temperature from 185°C to 150°C; consequently, more linalool was quantified in the films with improved content uniformity. The higher linalool content in the films increased the film disintegration time and mechanical strength. FDFs containing 10% w/w linalool showed clear antifungal activity against Candida albicans. Raman spectroscopy suggested linalool separation from excipients at higher temperature printing. Viscoelastic measurements indicated that to achieve printing; the elastic modulus of molten filament needed to be higher than the loss modulus at low angular frequencies. In conclusion, increasing the printing nozzle diameter may avoid loss of the active ingredient by reducing the temperature of the 3DP process.

EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer-2024 Update. Part I: Screening, Diagnosis, and Local Treatment with Curative Intent.

BACKGROUND AND OBJECTIVE: The European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Urological Pathology (ISUP)-International Society of Geriatric Oncology (SIOG) guidelines provide recommendations for the management of clinically localised prostate cancer (PCa). This paper aims to present a summary of the 2024 version of the EAU-EANM-ESTRO-ESUR-ISUP-SIOG guidelines on the screening, diagnosis, and treatment of clinically localised PCa. METHODS: The panel performed a literature review of all new data published in English, covering the time frame between May 2020 and 2023. The guidelines were updated, and a strength rating for each recommendation was added based on a systematic review of the evidence. KEY FINDINGS AND LIMITATIONS: A risk-adapted strategy for identifying men who may develop PCa is advised, generally commencing at 50 yr of age and based on individualised life expectancy. The use of multiparametric magnetic resonance imaging in order to avoid unnecessary biopsies is recommended. When a biopsy is considered, a combination of targeted and regional biopsies should be performed. Prostate-specific membrane antigen positron emission tomography imaging is the most sensitive technique for identifying metastatic spread. Active surveillance is the appropriate management for men with low-risk PCa, as well as for selected favourable intermediate-risk patients with International Society of Urological Pathology grade group 2 lesions. Local therapies are addressed, as well as the management of persistent prostate-specific antigen after surgery. A recommendation to consider hypofractionation in intermediate-risk patients is provided. Patients with cN1 PCa should be offered a local treatment combined with long-term intensified hormonal treatment. CONCLUSIONS AND CLINICAL IMPLICATIONS: The evidence in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. These PCa guidelines reflect the multidisciplinary nature of PCa management. PATIENT SUMMARY: This article is the summary of the guidelines for "curable" prostate cancer. Prostate cancer is "found" through a multistep risk-based screening process. The objective is to find as many men as possible with a curable cancer. Prostate cancer is curable if it resides in the prostate; it is then classified into low-, intermediary-, and high-risk localised and locally advanced prostate cancer. These risk classes are the basis of the treatments. Low-risk prostate cancer is treated with "active surveillance", a treatment with excellent prognosis. For low-intermediary-risk active surveillance should also be discussed as an option. In other cases, active treatments, surgery, or radiation treatment should be discussed along with the potential side effects to allow shared decision-making.

Exploring Unmet Needs in Prostate Cancer Care: A Cross-sectional Descriptive Study.

Background and objective: Prostate cancer, the most common cancer among men worldwide, has significant impact on quality of life. Supportive care needs for those affected by prostate cancer are not well understood. This study aims to describe patient-reported unmet needs and explore supportive care priorities of men treated for prostate cancer. Methods: A cross-sectional survey was distributed to all men who had accessed prostate cancer services (including surgical, radiation, and medical oncology treatment modalities) at a tertiary hospital. The survey included qualitative questions exploring patient experience and a validated patient-reported outcome measure (Supportive Care Needs Survey Short Form 34). Clinical information was collected. Analyses included, descriptive statistics, multivariate logistic regression models and qualitative analyses using a framework method. Key findings and limitations: A total of 162 participants provided survey data. Domains about information, self-management, and sexual function were the highest ranked items with unmet needs. A qualitative analysis also identified "relationships", "information", and "the value of hindsight" constructs. Participants who identified three or more unmet needs expressed treatment regret (odds ratio 5.92, 1.98-22.23, p = 0.01). Conclusions and clinical implications: Understanding the unmet needs of patients may better inform supportive care interventions that address what is important to patients. Importantly, participants valued relationships. There may be opportunities to better meet the needs of patients by improving access to information and self-management resources, particularly around sexuality. Further research is warranted. Patient summary: Prostate cancer and its treatment impacts are not well understood. Prioritisation of relationships and improving access to information and self-management resources are important. Further attention to prostate cancer supportive care in clinical practice is needed.

Association between diabetic status and risk of all-cause and cause-specific mortality on dialysis following first kidney allograft loss.

Background: Diabetes mellitus (DM) is associated with a greater risk of mortality in kidney transplant patients, primarily driven by a greater risk of cardiovascular disease (CVD)-related mortality. However, the associations between diabetes status at time of first allograft loss and mortality on dialysis remain unknown. Methods: All patients with failed first kidney allografts transplanted in Australia and New Zealand between 2000 and 2020 were included. The associations between diabetes status at first allograft loss, all-cause and cause-specific mortality were examined using competing risk analyses, separating patients with diabetes into those with pre-transplant DM or post-transplant diabetes mellitus (PTDM). Results: Of 3782 patients with a median (IQR) follow-up duration of 2.7 (1.1-5.4) years, 539 (14%) and 390 (10%) patients had pre-transplant DM or developed PTDM, respectively. In the follow-up period, 1336 (35%) patients died, with 424 (32%), 264 (20%) and 199 (15%) deaths attributed to CVD, dialysis withdrawal and infection, respectively. Compared to patients without DM, the adjusted subdistribution HRs (95% CI) for pre-transplant DM and PTDM for all-cause mortality on dialysis were 1.47 (1.17-1.84) and 1.47 (1.23-1.76), respectively; for CVD-related mortality were 0.81 (0.51-1.29) and 1.02 (0.70-1.47), respectively; for infection-related mortality were 1.84 (1.02-3.35) and 2.70 (1.73-4.20), respectively; and for dialysis withdrawal-related mortality were 1.71 (1.05-2.77) and 1.51 (1.02-2.22), respectively. Conclusions: Patients with diabetes at the time of kidney allograft loss have a significant survival disadvantage, with the excess mortality risk attributed to infection and dialysis withdrawal.

The effect of three years of vitamin D supplementation on erectile dysfunction: Results from the randomized placebo-controlled D-Health Trial.

BACKGROUND & AIMS: Erectile dysfunction is common among older men and has been associated with low serum 25-hydroxy vitamin D concentration. However, this association may be due to uncontrolled confounding, and there is a paucity of evidence from interventional studies. We aimed to examine the effect of vitamin D supplementation on the prevalence of erectile dysfunction, in an exploratory analysis using data from a large randomized controlled trial. METHODS: The D-Health Trial recruited Australians aged 60-84 years between January 2014 and May 2015 and randomly assigned them to supplementation with 60,000 IU of vitamin D or placebo per month for up to 5 years. Blood samples were collected annually from randomly selected participants (total N = 3943). We assessed erectile dysfunction at the end of the third year of follow-up. We used log-binomial regression to examine the effect of vitamin D on the prevalence of erectile dysfunction overall, and within sub-groups. RESULTS: Of the 11,530 men enrolled, 8920 (77.4 %) completed the erectile dysfunction question and were included in the analysis. After three years of supplementation, the mean serum 25-hydroxy vitamin D concentration was 76 nmol/L (standard deviation (SD) 24.94) in the placebo group and 106 nmol/L (SD 26.76) in the vitamin D group (p < 0.0001). The prevalence of erectile dysfunction was 58.8 % and 59.0 % in the vitamin D and placebo groups, respectively (prevalence ratio 1.00, 95 % CI 0.97, 1.03); there was no evidence of an effect of vitamin D in any subgroup analyses. CONCLUSION: Supplementing older men with vitamin D is unlikely to prevent or improve erectile dysfunction. CLINICAL TRIALS REGISTRY: (ACTRN12613000743763).

Etiology and management of urethral calculi: A systematic review of contemporary series.

Objective: To conduct a systematic literature review on urethral calculi in a contemporary cohort describing etiology, investigation, and management patterns. Methods: A systematic search of MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL) databases was performed. Articles, including case reports and case series on urethral calculi published between January 2000 and December 2019, were included. Full-text manuscripts were reviewed for clinical parameters including symptomatology, etiology, medical history, investigations, treatment, and outcomes. Data were collated and analyzed with univariate methods. Results: Seventy-four publications met inclusion criteria, reporting on 95 cases. Voiding symptoms (41.1%), pain (40.0%), and acute urinary retention (32.6%) were common presenting features. Urethral calculi were most often initially investigated using plain X-ray (63.2%), with almost all radio-opaque (98.3%). Urethral calculi were frequently associated with coexistent bladder or upper urinary tract calculi (16.8%) and underlying urethral pathology (53.7%) including diverticulum (33.7%) or stricture (13.7%). Urethral calculi were most commonly managed with external urethrolithotomy (31.6%), retrograde manipulation (22.1%), and endoscopic in situ lithotripsy (17.9%). Conclusion: This unique systematic review of urethral calculi provided a summary of clinical features and treatment trends with a suggested treatment algorithm. Management in contemporary urological practice should be according to calculus size, shape, anatomical location, and presence of urethral pathology.

The risk of prostate cancer on incidental finding of an avid prostate uptake on 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography for non-prostate cancer-related pathology: A single centre retrospective study.

Objective: To review the risk of prostate cancer (PCa) in men with incidentally reported increased intraprostatic uptake at 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) ordered at Department of Urology, The Wesley Hospital, Brisbane, QLD, Australia for non-PCa related pathology. Methods: Retrospective analysis of consecutive men between August 2014 and August 2019 presenting to a single institution for 18F-FDG PET/CT for non-prostate related conditions was conducted. Men were classified as benign, indeterminate, or malignant depending of the results of prostate-specific antigen (PSA), PSA velocity, biopsy histopathology, and three-Tesla (3 T) multiparametric MRI (mpMRI) Prostate Imaging Reporting and Data System score, or gallium-68-prostate-specific membrane antigen (68Ga-PSMA) PET/CT results. Results: Three percent (273/9122) of men demonstrated 18F-FDG avidity within the prostate. Eighty-five percent (231/273) were further investigated, including with PSA tests (227/231, 98.3%), 3 T mpMRI (68/231, 29.4%), 68Ga-PSMA PET/CT (33/231, 14.3%), and prostate biopsy (57/231, 24.7%). Results were considered benign in 130/231 (56.3%), indeterminate in 31/231 (13.4%), and malignant in 70/231 (30.3%). PCa was identified in 51/57 (89.5%) of the men who proceeded to biopsy, including 26/27 (96.3%) men with Prostate Imaging Reporting and Data System scores 4-5 mpMRI and six men with a positive 68Ga-PSMA PET/CT. The most common Gleason score on biopsy was greater than or equal to 4+5 (14/51, 27.5%). 68Ga-PSMA PET/CT was concordant with the 18F-FDG findings in 26/33 (78.8%). All 13 men with a positive concordant 18F-FDG, 3 T mpMRI, and 68Ga-PSMA PET/CT had PCa on biopsy. There was no statistically significant difference in the 18F-FDG maximum standardized uptake value between the benign or malignant groups (5.7 vs. 6.1; p=0.580). Conclusion: In this study, after an incidental finding of an avid intraprostatic lesion on 18F-FDG PET/CT, 70 of the 231 cases (30.3%; 0.8% of the entire cohort) had results consistent with PCa, most commonly as Gleason score greater than or equal to 4+5 disease. Unless there is limited life expectancy due to competing medical co-morbidity, men with an incidental finding of intraprostatic uptake on 18F-FDG should be further investigated using principles of PCa detection.

Clinical Adjudication of Hemodialysis Catheter-Related Bloodstream Infections: Findings from the REDUCCTION Trial.

BACKGROUND: Hemodialysis central venous catheter-related bloodstream infections (HD-CRBSI) are a significant source of morbidity and mortality among dialysis patients, but benchmarking remains difficult due to varying definitions of HD-CRBSI. This study explored the effect of clinical adjudication process on HD-CRBSI reporting. METHODS: The REDUcing the burden of Catheter ComplicaTIOns: a National approach (REDUCCTION) trial implemented an evidence-based intervention bundle using a stepped-wedge design to reduce HD-CRBSI rates in 37 Australian kidney services. Six New Zealand services participated in an observational capacity. Adult patients with a new hemodialysis catheter between December 2016 and March 2020 were included. HD-CRBSI events reported were compared to the adjudicated outcomes using the endpoint definition and adjudication processes of the REDUCCTION trial. The concordance level was estimated using Gwet's agreement coefficient (AC1) adjusted for service-level effects and implementation tranches (Australia only), with the primary outcome being the concordance of confirmed HD-CRBSI. RESULTS: A total of 744 hemodialysis catheter-related infectious events were reported among 7,258 patients, 12,630 catheters and 1.3 million catheter-exposure days. The majority were confirmed HD-CRBSI, with 77.9% agreement and 'substantial' concordance (AC1=0.77, 95% confidence interval [CI]: 0.73, 0.81). Exit site infections have the highest concordance (AC1=0.85, 95% CI 0.78, 0.91); the greatest discordance was in events classified as Other (AC1=0.33, 95% CI 0.16, 0.49). The concordance of all hemodialysis catheter infectious events remained 'substantial' (AC1=0.80, 95% CI 0.76, 0.83) even after adjusting for the intervention tranches in Australia and overall service-level clustering. CONCLUSIONS: There was a substantial level of concordance in overall and service-level reporting of confirmed HD-CRBSI. A standardized endpoint definition of HD-CRBSI resulted in comparable hemodialysis catheter infection rates in Australian and New Zealand kidney services. Consistent endpoint definition could enable reliable benchmarking outside clinical trials without the need for independent clinical adjudication.

The impact of management option on out-of-pocket costs and perceived financial burden among men with localised prostate cancer in Australia within 6 months of diagnosis.

Objective This study aimed to quantify the out-of-pocket (OOP) costs and perceived financial burden among Australian men with localised prostate cancer in the first 6 months after diagnosis, by primary management option. Methods This cost-analysis quantified OOP costs using administrative claims data and self-reported survey data. Financial burden was assessed using the COmprehensive Score for financial Toxicity-Functional Assessment of Chronic Illness Therapy (COST-FACIT) tool. Participants were recruited into a randomised control trial from public or private treatment centres in Victoria and Queensland. Generalised linear models were used to predict OOP costs and COST-FACIT scores. Results Median total OOP costs within 6 months of diagnosis for 256 Australian patients with localised prostate cancer was A$1172 (A$343-2548). Up to 50% of the sample reported A$0 costs for most medical services. Compared with those managed with active surveillance, men having active treatment had 6.4 (95% CI: 3.2-12.7) times greater total OOP costs. Management option, higher Gleason score at diagnosis and having multiple comorbidities were significant predictors of higher OOP costs. Overall high scores on the COST-FACIT indicated low levels of financial burden for the entire sample. Conclusion Largely attributable to being managed with active surveillance, Australian men diagnosed with localised prostate cancer reported relatively low OOP costs and financial burden in the first 6 months post-diagnosis. Together with clinical outcomes, clinicians can use this up to date evidence on costs and perceived financial burdens to assist localised prostate cancer patients and their families make informed decisions about their preferred management option.

Patient-Centric Quality Standards.

To ensure the quality, safety and efficacy of medicinal products, it is necessary to develop and execute appropriate manufacturing process and product control strategies. Traditionally, product control strategies have focused on testing known quality attributes with limits derived from levels administered in preclinical and clinical studies with an associated statistical analysis to account for variability. However, not all quality attributes have impact to the patient and those with the potential to impact safety and efficacy may not be significant when dosed at patient-centric levels. Therefore, achieving patient-centricity is understanding patient relevance, which is defined as the level of impact that a quality attribute could have on safety and efficacy within the potential exposure range. A patient-centric quality standard (PCQS) is therefore a set of patient relevant attributes and their associated acceptance ranges to which a drug product should conform within the expected patient exposure range. This manuscript describes historical perspectives details the way to create and leverage a PCQS in a variety of pharmaceutical product modalities.

The Role of Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography in Primary Staging of Selected Renal Tumours: Initial Experience in a Multicentre Cohort.

BACKGROUND: Accurate primary staging of renal cancer with conventional imaging is challenging. Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) may serve to improve the accuracy of renal cancer staging. OBJECTIVE: To determine clinicopathological and management differences for primary renal cancer staged with PSMA PET/CT in comparison to conventional imaging. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective cohort study of PSMA PET/CT scans performed for primary staging of renal cancer and incidental renal lesions at three sites in Brisbane, Australia between June 2015 and June 2020. Clinical characteristics, imaging, and histopathology were reviewed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Clinicopathological and management differences according to staging modality (PSMA PET/CT, conventional imaging) were assessed. Descriptive statistics were used to report demographics and clinical parameters. Nonparametric methods were used for statistical analysis. Fisher's exact test was used for comparison of small-cell size categorical variables. RESULTS AND LIMITATIONS: From a total of 120 PSMA PET/CT scans, 61 were included (52 staging, 9 incidental) for predominantly males (74%) with a mean age of 65.1 yr (standard deviation 12.0). Most primary lesions (40/51) were clear-cell renal cell carcinoma (ccRCC; 98% PSMA-avid), eight were non-ccRCC (75% PSMA-avid), and three were non-RCC (oncocytoma; 67% PSMA-avid). PSMA PET identified a greater number of presumed metastatic lesions than conventional imaging (195 vs 160). A management change was observed for 32% of patients (20% major, 12% minor). Limitations include the retrospective design and selection bias, lack of blinding to PSMA reporting, and the use of different PSMA radiotracers. CONCLUSIONS: PSMA PET/CT detected more metastases than conventional imaging and most renal cancers were PSMA-avid, resulting in a management change for one-third of the patients. PATIENT SUMMARY: We looked at a newer type of scan called PSMA PET/CT for first staging of kidney cancer. We found that this detects more metastasis and helps in decisions on changes in treatment for some patients. This type of imaging is a useful addition to conventional scans in tricky cases and may help in better selection of suitable treatments, but more studies are required.

Avoiding misclassification of acute kidney injury: Timing is everything.

Accurate detection of acute kidney injury (AKI) in clinical trials is important. Using a 'baseline' creatinine from trial enrolment may not be ideal for understanding a participant's true baseline kidney function. We aimed to determine if a 'pre-trial baseline creatinine' resulted in comparable creatinine concentrations to a 'trial baseline creatinine', and how the timing of baseline creatinine affected the incidence of AKI in the Combination Antibiotic therapy for MEthicillin Resistant Staphylococcus aureus (CAMERA2) randomised trial. Study sites retrospectively collected a pre-trial baseline creatinine from up to 1 year before CAMERA2 trial enrolment ideally when the patient was medically stable. Baseline creatinine from CAMERA2 (the 'trial baseline creatinine'), was the highest creatinine measurement in the 24 h preceding trial randomisation. We used Wilcoxon sign rank test to compare pre-trial and trial baseline creatinine concentrations. We included 217 patients. The median pre-trial baseline creatinine was significantly lower than the median trial baseline creatinine (82 µmol/L [IQR 65-104 µmol/L] versus 86 µmol/L [IQR 66-152 µmol/L] p = <0.001). Using pre-trial baseline creatinine, 48 of 217 patients (22%) met criteria for an AKI at CAMERA2 enrolment and only 5 of these patients met criteria for an AKI using the CAMERA2 study protocol (using baseline creatinine from trial entry). Using a baseline creatinine from the time of trial enrolment failed to detect many patients with AKI. Trial protocols should consider the optimal timing of baseline creatinine and the limitations of using a baseline creatinine during an acute illness.

Reproducibility and Accuracy of the PRIMARY Score on PSMA PET and of PI-RADS on Multiparametric MRI for Prostate Cancer Diagnosis Within a Real-World Database.

The PRIMARY score is a 5-category scale developed to identify clinically significant intraprostate malignancy (csPCa) on 68Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT (68Ga-PSMA PET) using a combination of anatomic site, pattern, and intensity. Developed within the PRIMARY trial, the score requires evaluation in external datasets. This study aimed to assess the reproducibility and diagnostic accuracy of the PRIMARY score in a cohort of patients who underwent multiparametric MRI (mpMRI) and 68Ga-PSMA PET before prostate biopsy for the diagnosis of prostate cancer. Methods: In total, data from 242 men who had undergone 68Ga-PSMA PET and mpMRI before transperineal prostate biopsy were available for this ethics-approved retrospective study. 68Ga-PSMA PET and mpMRI data were centrally collated in a cloud-based deidentified image database. Six experienced prostate-focused nuclear medicine specialists were trained (1 h) in applying the PRIMARY score with 30 sample images. Six radiologists experienced in prostate mpMRI read images as per the Prostate Imaging-Reporting and Data System (PI-RADS), version 2.1. All images were read (with masking of clinical information) at least twice, with discordant findings sent to a masked third (or fourth) reader as necessary. Cohen κ was determined for both imaging scales as 5 categories and then collapsed to binary (negative and positive) categories (score 1 or 2 vs. 3, 4, or 5). Diagnostic performance parameters were calculated, with an International Society of Urological Pathology grade group of at least 2 (csPCa) on biopsy defined as the gold standard. Combined-imaging-positive results were defined as any PI-RADS score of 4 or 5 or as a PI-RADS score of 1-3 with a PRIMARY score of 3-5. Results: In total, 227 patients with histopathology, 68Ga-PSMA PET, and mpMRI imaging before prostate biopsy were included; 33% had no csPCa, and 67% had csPCa. Overall interrater reliability was higher for the PRIMARY scale (κ = 0.70) than for PI-RADS (κ = 0.58) when assessed as a binary category (benign vs. malignant). This was similar for all 5 categories (κ = 0.65 vs. 0.48). Diagnostic performance to detect csPCa was comparable between PSMA PET and mpMRI (sensitivity, 86% vs. 89%; specificity, 76% vs. 74%; positive predictive value, 88% vs. 88%; negative predictive value, 72% vs. 76%). Using combined imaging, sensitivity was 94%, specificity was 68%, positive predictive value was 86%, and negative predictive value was 85%. Conclusion: The PRIMARY score applied by first-user nuclear medicine specialists showed substantial interrater reproducibility, exceeding that of PI-RADS applied by mpMRI-experienced radiologists. Diagnostic performance was similar between the 2 modalities. The PRIMARY score should be considered when interpreting intraprostatic PSMA PET images.

Intra-individual comparison of prostate-specific membrane antigen positron emission tomography/computed tomography versus bone scan in detecting skeletal metastasis at prostate cancer diagnosis.

OBJECTIVES: To compare the diagnostic performance and radiological staging impact of 68 Ga-prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) compared to 99 Tc whole-body bone scan (WBBS) for the detection of skeletal metastasis in the primary staging of prostate cancer (PCa). PATIENTS AND METHODS: A prospective institutional database was retrospectively examined for patients who underwent both PSMA PET and WBBS within a 1 week interval for PCa primary staging. Lesions were categorised as 'negative', 'equivocal', or 'definite' based on nuclear medicine physician interpretation. Metastatic burden was characterised for each imaging modality according to three groups: (i) local disease (no skeletal metastases), (ii) oligometastatic disease (three or fewer skeletal metastases), or (iii) polymetastatic disease (more than three skeletal metastases). RESULTS: There were 667 patients included. The median (interquartile range) prostate-specific antigen level was 9.2 (6.2-16) ng/mL and 60% of patients were high risk according to a modified D'Amico risk classification. The overall distribution of skeletal metastasis detection changed across the two scans overall (P = 0.003), being maintained within high-risk (P = 0.030) and low-risk (P = 0.018) groups. PSMA PET/CT identified more definite skeletal metastases compared to WBBS overall (10.3% vs 7.3%), and according to risk grouping (high: 12% vs 9%, intermediate: 4% vs 1%). Upstaging was more common with PSMA PET/CT than WBBS (P = 0.001). The maximum standardised uptake value (SUVmax ) of the primary tumour was associated with upstaging of skeletal metastases on PSMA PET/CT (P = 0.025), while age was associated with upstaging on WBBS (P = 0.021). The SUVmax of the primary tumour and metastases were both higher according to extent of metastatic disease (P = 0.001 and P < 0.001, respectively). CONCLUSIONS: More skeletal metastases were detected with PSMA PET/CT than WBBS, resulting in a higher upstaging rate mostly in high-risk patients. The SUVmax of the primary tumour and metastases was associated with upstaging.

The Dedicated Imaging Post-Prostatectomy for Enhanced Radiotherapy outcomes (DIPPER) trial protocol: a multicentre, randomised trial of salvage radiotherapy versus surveillance for low-risk biochemical recurrence after radical prostatectomy.

BACKGROUND: Salvage radiation therapy (SRT) and surveillance for low-risk prostate-specific antigen (PSA) recurrence have competing risks and benefits. The efficacy of early SRT to the prostate bed with or without pelvic lymph nodes compared to surveillance in patients with PSA recurrence after radical prostatectomy and no identifiable recurrent disease evident on prostate specific membrane antigen-positron emission tomography/computer tomography (PSMA-PET/CT) is unknown. STUDY DESIGN: The Dedicated Imaging Post-Prostatectomy for Enhanced Radiotherapy outcomes (DIPPER) is an open-label, multicentre, randomised Phase II trial. ENDPOINTS: The primary endpoint is 3-year event-free survival, with events comprising one of PSA recurrence (PSA ≥0.2 ng/mL higher than baseline), radiological evidence of metastatic disease, or initiation of systemic or other salvage treatments. Secondary endpoints include patient-reported outcomes, treatment patterns, participant perceptions, and cost-effectiveness. ELIGIBILITY CRITERIA: Eligible participants have PSA recurrence of prostate cancer after radical prostatectomy, defined by serum PSA level of 0.2-0.5 ng/mL, deemed low risk according to modified European Association of Urology biochemical recurrence risk criteria (International Society for Urological Pathology Grade Group ≤2, PSA doubling time >12 months), with no definite/probable recurrent prostate cancer on PSMA-PET/CT. PATIENTS AND METHODS: A total of 100 participants will be recruited from five Australian centres and randomised 1:1 to SRT or surveillance. Participants will undergo 6-monthly clinical evaluation for up to 36 months. Androgen-deprivation therapy is not permissible. Enrolment commenced May 2023. TRIAL REGISTRATION: This trial has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN: ACTRN12622001478707).

Are There Interindividual Responses of Cardiovascular Disease Risk Markers to Acute Exercise? A Replicate Crossover Trial.

PURPOSE: Using a replicated crossover design, we quantified the response heterogeneity of postprandial cardiovascular disease risk marker responses to acute exercise. METHODS: Twenty men (mean (SD) age, 26 (6) yr; body mass index, 23.9 (2.4) kg·m -2 ) completed four 2-d conditions (two control, two exercise) in randomized orders. On days 1 and 2, participants rested and consumed two high-fat meals over 9 h. Participants ran for 60 min (61 (7)% of peak oxygen uptake) on day 1 (6.5 to 7.5 h) of both exercise conditions. Time-averaged total area under the curve (TAUC) for triacylglycerol, glucose, and insulin were calculated from 11 venous blood samples on day 2. Arterial stiffness and blood pressure responses were calculated from measurements at baseline on day 1 and at 2.5 h on day 2. Consistency of individual differences was explored by correlating the two replicates of control-adjusted exercise responses for each outcome. Within-participant covariate-adjusted linear mixed models quantified participant-by-condition interactions and individual response SDs. RESULTS: Acute exercise reduced mean TAUC-triacylglycerol (-0.27 mmol·L -1 ·h; Cohen's d = 0.29, P = 0.017) and TAUC-insulin (-25 pmol·L -1 ·h; Cohen's d = 0.35, P = 0.022) versus control, but led to negligible changes in TAUC-glucose and the vascular outcomes (Cohen's d ≤ 0.36, P ≥ 0.106). Small-to-moderate, but nonsignificant, correlations were observed between the two response replicates ( r = -0.42 to 0.15, P ≥ 0.066). We did not detect any individual response heterogeneity. All participant-by-condition interactions were P ≥ 0.137, and all individual response SDs were small with wide 95% confidence intervals overlapping zero. CONCLUSIONS: Large trial-to-trial within-subject variability inhibited detection of consistent interindividual variability in postprandial metabolic and vascular responses to acute exercise.