Fluorine-18-labelled Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography or Magnetic Resonance Imaging to Diagnose and Localise Prostate Cancer. A Prospective Single-arm Paired Comparison (PEDAL).

BACKGROUND AND OBJECTIVE: Multiparametric magnetic resonance imaging (mpMRI) of the prostate is used for prostate cancer diagnosis. However, mpMRI has lower sensitivity for small tumours. Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) offers increased sensitivity over conventional imaging. This study aims to determine whether the diagnostic accuracy of 18F-DCFPyL PSMA-PET/CT was superior to that of mpMRI for detecting prostate cancer (PCa) at biopsy. METHODS: Between 2020 and 2021, a prospective multicentre single-arm phase 3 imaging trial enrolled patients with clinical suspicion for PCa to have both mpMRI and PSMA-PET/CT (thorax to thigh), with reviewers blinded to the results of other imaging. Multiparametric MRI was considered positive for Prostate Imaging Reporting and Data System (PIRADS) 3-5. PSMA-PET/CT was assessed quantitatively (positive maximum standardised uptake value [SUVmax] >7) and qualitatively (five-point lexicon of certainty). Patients underwent targeted and systematic biopsy, with the technique at the discretion of the treating urologist. Clinically significant PCa (csPCa) was defined as International Society of Urological Pathology grade group (GG) ≥2. The primary outcome was the diagnostic accuracy for detecting PCa, reported as sensitivity, specificity, negative predictive value (NPV), and area under the curve (AUC) of the receiver operating curve. The secondary endpoints included a comparison of the diagnostic accuracy for detecting csPCa, assessing gains in combining PMSA-PET/CT with mpMRI to mpMRI alone. KEY FINDINGS AND LIMITATIONS: Of the 236 patients completing both mpMRI and PSMA-PET/CT, 184 (76.7%) had biopsy. Biopsy histology was benign (n = 73), GG 1 (n = 27), and GG ≥2 (n = 84). The diagnostic accuracy of mpMRI for detecting PCa (AUC 0.76; 95% confidence interval [CI] 0.69, 0.82) was higher than that of PSMA-PET/CT (AUC 0.63; 95% CI 0.56, 0.70, p = 0.03). The diagnostic accuracy of mpMRI for detecting csPCa (AUC 0.72; 95% CI 0.67, 0.78) was higher than that of PSMA-PET/CT (AUC 0.62; 95% CI 0.55, 0.69) but not statistically significant (p = 0.27). A combination of PSMA-PET/CT and mpMRI showed excellent sensitivity (98.8%, 95% CI 93.5%, 100%) and NPV (96%, 95% CI 79.6%, 99.9%) over mpMRI alone (86.9% and 80.7%, respectively, p = 0.01). Thirty-two patients (13.6%) had metastatic disease. They tended to be older (68.4 vs 65.1 yr, p = 0.023), and have higher prostate-specific antigen (PSA; median PSA 9.6 vs 6.2ng/ml, p < 0.001) and abnormal prostate on digital rectal examination (78.2% vs 44.1%, p < 0.001). CONCLUSIONS AND CLINICAL IMPLICATIONS: Multiparametric MRI had superior diagnostic accuracy to PSMA-PET/CT for detecting PCa, though the difference is not significant in case of csPCa detection. A combination of mpMRI and PSMA-PET/CT showed improved sensitivity and NPV. PSMA-PET/CT could be considered for diagnostic use in patients unable to have mpMRI or those with concerning clinical features but negative mpMRI. PATIENT SUMMARY: In this trial, we compared the ability of 18F-labelled prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) with that of multiparametric magnetic resonance imaging (mpMRI) to diagnose prostate cancer by biopsy in a prostate-specific antigen screening population. We found that MRI was superior to PSMA to diagnose prostate cancer, though there was no difference in ability to diagnose clinically significant prostate cancer. PSMA-PET/CT could be considered for diagnostic use in patients unable to have mpMRI or those with concerning clinical features but negative mpMRI. Combining MRI with PSMA-PET increases the negative predictive value over MRI alone and may help men avoid invasive prostate biopsy.

PEDAL protocol: a prospective single-arm paired comparison of multiparametric MRI and 18F-DCPFyl PSMA PET/CT to diagnose prostate cancer.

INTRODUCTION: Prostate-specific membrane antigen positron emission tomography (PSMA-PET) has emerged as valuable imaging to assessing metastatic disease in prostate malignancy. However, there has been limited studies exploring the utility PSMA-PET as primary imaging assessing for index lesions prior to biopsy. The primary objective of this study is to compare the diagnostic accuracy of 18-fluorine PSMA (18F DCFPyL PSMA) PET scans to multiparametric MRI (mpMRI) to detect primary prostate cancer at prostate biopsy. METHODS AND ANALYSIS: The PEDAL trial is a multicentre, prospective, single-arm, paired comparison, non-randomised phase III trial in subjects considered for diagnostic prostate biopsy. Subjects who are eligible for a diagnostic mpMRI prostate will undergo additional same-day 18 F DCFPyl PSMA PET/CT of the chest, abdomen and pelvis. Software coregistration of the mpMRI and PSMA-PET/CT images will be performed. The reporting of the mpMRI prostate, PSMA-PET/CT and PSMA PET/MRI coregistration will be performed blinded. The diagnostic accuracy of PSMA PET/CT alone, and in combination with mpMRI, to detect prostate cancer will be assessed. Histopathology at prostate biopsy will be used as the reference standard. Sample size calculations estimate that 240 subjects will need to be recruited to demonstrate 20% superiority of PSMA-PET/CT. The sensitivity, specificity, positive predictive value and negative predictive value of the combination of mpMRI prostate and PSMA PET/CT compared with targeted and systematic prostate biopsy will be evaluated. It is hypothesised that PSMA PET/CT combined with mpMRI prostate will have improved diagnostic accuracy compared with mpMRI prostate alone for detection of prostate cancer in biopsy-naïve men, resulting in a significant impact on patient management. ETHICS AND DISSEMINATION: This study was approved by the independent Human Research Ethics Committee. Results will be published in peer-reviewed medical journals with eligible investigators will significantly contribute. TRIAL REGISTRATION NUMBER: ACTRN12620000261910.

Evaluation of community-based CT abdomen for acute abdominal pain during COVID-19.

AIM: The purpose of this study was to determine the utility of community-based imaging to reduce use of inpatient surgical resources and enforce social distancing at the outset of the COVID-19 pandemic. METHOD: A prospective evaluation of community-based CT for patients presenting to Christchurch general practitioners with acute abdominal pain from April to November 2020. Eligible patients were discussed with the on-call general surgical team, and then referred for CT abdomen rather than hospital assessment. The positivity rate of CT scans, the 30-day all-cause hospital admission rate, and the proportion of patients where community scanning altered management setting and the number of incidental findings, were all assessed. RESULTS: Of 131 included patients, 67 (51%) patients had a positive CT scan. Thirty-nine (30%) patients were admitted to hospital within 30 days, 34 (87%) of whom had a positive CT scan and were admitted under a surgical specialty. Ninety-two (70%) patients did not require hospital admission for their acute abdominal pain, thirty-three (35%) of whom had a positive CT scan. There were three deaths within 30 days of the community CT, and the setting of the community CT did not contribute to the death of any of the cases. Forty patients (30%) had incidental findings on CT, 10 (25%) of which were significant and were referred for further investigation. CONCLUSION: Community based abdominal CT scanning is a feasible option in the management of acute abdominal pain. While trialed in response to the initial nationwide COVID-19 lockdown in New Zealand, there may be utility for acute community-based CT scanning in regular practice.

Combination of MRI prostate and 18F-DCFPyl PSMA PET/CT detects all clinically significant prostate cancers in treatment-naive patients: An international multicentre retrospective study.

INTRODUCTION: Clinical and biochemical assessment and biopsies can miss clinically significant prostate cancers (csPCa) in up to 20% of patients and diagnose clinically insignificant tumours leading to overtreatment. This retrospective study analyses the accuracy of 18 F-DCFPyL PET/CT in detecting csPCa as a primary diagnostic tool and directly compares it with mpMRI prostate in treatment-naive patients. The two modalities are then correlated to determine whether they are better in combination, than either alone. METHODS: This is a retrospective dual-institution study of patients who underwent contemporaneous MRI and PSMA-PET between January 2017 and March 2020 with histologic confirmation. The images were re-reviewed and concordance between modalities assessed. Results were compared with histopathology to determine the ability of MRI and PSMA-PET to detect csPCA. RESULTS: MRI and PSMA-PET detected the same index lesion in 90.8% of cases with a kappa of 0.82. PET detected an additional 6.2% of index lesions which were MRI occult. MRI detected an additional 3.1% which were PET occult. No additional csPCa was identified on pathology which was not seen on imaging. The sensitivity of PSMA-PET in detecting csPCa is 96.7% and that of MRI is 93.4% with no statistically significant difference between the two (P = 0.232). Both modalities detected all four cases of non-csPCa with these being considered false positives. CONCLUSION: Both mpMRI and 18F-DCFPyL-PSMA-PET/CT have high sensitivity for detecting csPCa with high agreement between modalities. There were no synchronous csPCa lesions detected on pathology that were not detected on imaging too.

Resilience and Equity in a Time of Crises: Investing in Public Urban Greenspace Is Now More Essential Than Ever in the US and Beyond.

The intersecting negative effects of structural racism, COVID-19, climate change, and chronic diseases disproportionately affect racial and ethnic minorities in the US and around the world. Urban populations of color are concentrated in historically redlined, segregated, disinvested, and marginalized neighborhoods with inadequate quality housing and limited access to resources, including quality greenspaces designed to support natural ecosystems and healthy outdoor activities while mitigating urban environmental challenges such as air pollution, heat island effects, combined sewer overflows and poor water quality. Disinvested urban environments thus contribute to health inequity via physical and social environmental exposures, resulting in disparities across numerous health outcomes, including COVID-19 and chronic diseases such as cancer and cardiovascular diseases (CVD). In this paper, we build off an existing conceptual framework and propose another conceptual framework for the role of greenspace in contributing to resilience and health equity in the US and beyond. We argue that strategic investments in public greenspaces in urban neighborhoods impacted by long term economic disinvestment are critically needed to adapt and build resilience in communities of color, with urgency due to immediate health threats of climate change, COVID-19, and endemic disparities in chronic diseases. We suggest that equity-focused investments in public urban greenspaces are needed to reduce social inequalities, expand economic opportunities with diversity in workforce initiatives, build resilient urban ecosystems, and improve health equity. We recommend key strategies and considerations to guide this investment, drawing upon a robust compilation of scientific literature along with decades of community-based work, using strategic partnerships from multiple efforts in Milwaukee Wisconsin as examples of success.

The scratch test for identifying the lower liver edge is at least as accurate as percussion and is significantly more effective for young trainees-a randomised comparative trial.

BACKGROUND: Clinical examination of the liver requires experience to achieve accuracy. The scratch test is a simple technique to identify the lower liver edge and enhance liver palpation, and may be easier for trainees. AIM: We aimed to evaluate the accuracy of the scratch test compared to percussion at different levels of medical training. METHOD: Eight examiners, from trainee intern to consultant level, were randomised to scratch or percussion testing, followed by liver palpation, on 50 subjects. Later, each examiner performed the alternative test on each subject. Confidence with each test was rated 0-3 (unsuccessful-very confident). Ultrasound scan (US) was performed as a reference for liver location. RESULTS: Ultrasound revealed 33/50 (66%) of livers extended below the right costal margin in the midclavicular line during quiet respiration (range 0.5-16cm). Of these, 33, 87% and 76% were identified within 2cm of the US location using scratch and percussion tests, respectively (p>0.05) for all examiners, but with significantly greater accuracy for the scratch test in young trainees (91% v 75%; p=0.016). Ability to palpate the liver was not different following either test. The training effect was assessed by comparing the accuracy results of the first 25 with the last 25 examined subjects, revealing a significant increase in accuracy with percussion from 71% to 85% (p=0.038) compared to no change with the scratch test (88% and 86%). Examiner confidence in the test result was significantly higher using the scratch test versus percussion, average confidence scores being 2.2 versus 1.8 (p<0.001), with a greater difference in the young trainee group at 2.4 versus 1.7 (p<0.001). CONCLUSION: The scratch test was at least as accurate as percussion overall in identifying the lower liver edge and significantly more accurate for the young trainees. The scratch test requires less training and in addition, all examiners and especially the young trainees were significantly more confident in their findings using the scratch test.

Legionnaires' disease caused by Legionella longbeachae: Clinical features and outcomes of 107 cases from an endemic area.

BACKGROUND AND OBJECTIVE: Legionella longbeachae is a predominant cause of Legionnaires' disease in some parts of the world, particularly in Australasia. Clinical reports of L. longbeachae infection are limited to case reports or small case series, and culture-confirmed cases. METHODS: We reviewed the clinical characteristics and outcomes of L. longbeachae pneumonia in a large case series from Christchurch, New Zealand during a 4-year period when both PCR and cultures were used as routine diagnostic tools for Legionnaires' disease. Cases of Legionella pneumophila pneumonia were reviewed for comparison. RESULTS: A total of 107 cases of L. longbeachae infection were identified by PCR and/or culture. The median age was 65 years (range 25-90 years), 63% were male, and most became unwell during spring or summer. Presenting clinical features were similar to those reported for community-acquired pneumonia, with headache, myalgia and diarrhoea being common. Elevated C-reactive protein, hyponatraemia and abnormal liver function tests were also common. History of productive cough, involvement of both lungs, and high bacterial load were independently associated with culture of Legionella from lower respiratory samples. One quarter required intensive care unit admission, and 5% died. Among patients given antimicrobial therapy before admission, those given agents without anti-Legionella activity were more likely to be admitted to the intensive care unit. Limited comparisons were made with the 19 L. pneumophila cases over the same time period. CONCLUSION: Characteristics of L. longbeachae pneumonia are broadly similar to those reported for community-acquired pneumonia from a variety of other populations, except for the spring/summer seasonality.