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Context Staging, restaging, and surveillance of urothelial carcinoma (UC) is challenging due to suboptimal accuracy of standard of care imaging modalities. Prostate-specific membrane antigen (PSMA) imaging may serve to improve characterisation of UC. Objective To appraise available literature regarding cellular, imaging, and prognostic implications of PSMA for UC. Evidence acquisition A systematic review was performed considering all available literature (including conference abstracts) published from 1990 to 2020 and reported according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines following registration in PROSPERO (CRD42020186744). All relevant texts relating to immunohistochemical analysis and PSMA-based imaging in UC were included and collated. Additionally, FOLH1 (gene encoding PSMA) expression according to The Cancer Genome Atlas (TCGA) database was analysed as well as according to consensus and TCGA molecular classification subtypes and subsequently compared with clinical outcomes. Evidence synthesis PSMA expression across UC tumour tissue was heterogeneous (0–100%) but appeared to decrease with increased grade and stage. The TCGA analysis demonstrated loss of FOLH1 expression with increasing T stage (p = 0.0180) and N stage (p = 0.0269), and reduced FOLH1 expression was associated with worse disease-free survival. PSMA expression in UC neovasculature was variable but mostly increased (44–100%). Eleven reports of PSMA-based imaging for UC were identified, reporting on 18 patients. PSMA positron emission tomography (PET) imaging was positive in 17 out of 18 patients. The included literature review data were limited by mostly low-quality, retrospective studies. Conclusions Tissue PSMA, or FOLH1 expression, may inversely be associated with pathological and survival outcomes in localised UC. PSMA PET imaging may improve detection of metastatic disease and response to systemic therapy due to PSMA expression in neovasculature. Available evidence is limited; thus, larger, prospective studies are required to confirm early results and define populations that benefit most. Patient summary In this systematic review, we assess the potential role of prostate-specific membrane antigen in urothelial cancer. We found that its utility is in expression of blood vessels surrounding metastasis. We conclude that it may be beneficial in detecting metastasis and response to systemic therapies.

Purpose:Multiparametric magnetic resonance imaging (mpMRI) fails to identify some men with significant prostate cancer. Prostate-specific membrane antigen positron emission tomography/computerized ...

Multiparametric magnetic resonance imaging (MRI) is validated for the detection of clinically significant prostate cancer (csPCa), although patients with negative/equivocal MRI undergo biopsy for false negative concerns. In addition,This trial aimed to determine whether the combination of PSMA + MRI was superior to MRI in diagnostic performance for detecting csPCa.A prospective multicentre phase II imaging trial was conducted. A total of 296 men were enrolled with suspected prostate cancer, with no prior biopsy or MRI, recent MRI (6 mo), and planned transperineal biopsy based on clinical risk and MRI. In all, 291 men underwent MRI, pelvic-only PSMA, and systematic ± targeted biopsy.Sensitivity, specificity, and predictive values (negative predictive value [NPV] and positive predictive value) for csPCa were determined for MRI, PSMA, and PSMA + MRI. PSMA + MRI was defined as negative for PSMA negative Prostate Imaging Reporting and Data System (PI-RADS) 2/3 and positive for either MRI PI-RADS 4/5 or PSMA positive PI-RADS 2/3; csPCa was any International Society of Urological Pathology (ISUP) grade group ≥2 malignancy.Of the patients, 56% (n = 162) had csPCa; 67% had PI-RADS 3-5, 73% were PSMA positive, and 81% were combined PSMA + MRI positive. Combined PSMA + MRI improved NPV compared with MRI alone (91% vs 72%, test ratio = 1.27 [1.11-1.39], p 0.001). Sensitivity also improved (97% vs 83%, p 0.001); however, specificity was reduced (40% vs 53%, p = 0.011). Five csPCa cases were missed with PSMA + MRI (four ISUP 2 and one ISUP 3). Of all men, 19% (56/291) were PSMA + MRI negative (38% of PI-RADS 2/3) and could potentially have avoided biopsy, risking delayed csPCa detection in 3.1% men with csPCa (5/162) or 1.7% (5/291) overall.PSMA + MRI improved NPV and sensitivity for csPCa in an MRI triaged population. Further randomised studies will determine whether biopsy can safely be omitted in men with a high clinical suspicion of csPCa but negative combined imaging.The combination of magnetic resonance imaging (MRI) + prostate-specific membrane antigen positron emission tomography reduces false negatives for clinically significant prostate cancer (csPCa) compared with MRI, potentially allowing a reduction in the number of prostate biopsies required to diagnose csPCa.

BACKGROUND Incremental peritoneal dialysis (PD) is recommended as a component of high-quality care by the international society for PD; however, its feasibility and clinical outcomes have not been widely reported. The aim of this study is to describe our experience with incremental PD. METHODS This was a retrospective cohort study of incident PD patients at Eastern Health between 2015 and 2019. Patients who stopped PD within 30 days were excluded. Incremental PD was defined in CAPD as using

Melanoma is rare in pediatric patients and even more so in those with darker Fitzpatrick skin types. Although risk factors for conventional melanoma are similar in both adult and pediatric cases, the presentation of melanoma in pediatric patients is often distinct from adults. Here, we describe a case of amelanotic ulcerated nodular melanoma with regional lymph node metastases treated with nivolumab in a patient with Fitzpatrick skin type VI.

[18F]PSMA-1007 has potential advantages over [68 Ga]Ga-PSMA-11, although limited prospective data evaluating diagnostic performance exist. The aims of this study are to describe the concordance of [18FPSMA-1007 and [68 Ga]Ga-PSMA-11 for TNM with the American Joint Committee on Cancer (AJCC) prognostic stage and assess differences in tracer uptake. Fifty men (mean age 71.8) were imaged with [68 Ga]Ga-PSMA-11 and [18F]PSMA-1007

[18F]PSMA-1007 offers advantages of low urinary tracer excretion and theoretical improved spatial resolution for imaging prostate cancer. However, non-specific bone lesions (NSBLs), defined as mild to moderate focal bone uptake without a typical morphological correlate on CT, are a common finding on [18F]PSMA-1007 PET/CT. The purpose of this study was to investigate the clinical outcomes of patients with [18F]PSMA-1007 avid NSBLs, to determine whether patients with NSBLs represent a higher risk clinical cohort, and to determine whether SUVmax can be used as a classifier of bone metastasis. A retrospective audit of 214 men with prostate cancer was performed to investigate the clinical outcomes of [18F]PSMA-1007 avid NSBLs according to defined criteria. We also compared the serum PSA, Gleason score, and uptake time of patients with [18F]PSMA-1007 avid NSBLs to patients without [18F]PSMA-1007 avid bone lesions. Finally, we analysed an SUVmax threshold to identify bone metastases using ROC curve analysis. Ninety-four of 214 patients (43.9%) demonstrated at least one NSBL. No [18F]PSMA-1007 avid NSBLs met criteria for a likely malignant or definitely malignant lesion after a median 15.8-month follow-up interval (11.9% definitely benign, 50.3% likely benign, and 37.7% equivocal). There were no statistically significant differences in serum PSA, Gleason score, and uptake time between patients with [18F]PSMA-1007 avid NSBLs and those without [18F]PSMA-1007 avid bone lesions. All NSBLs with adequate follow-up had SUVmax ≤ 11.1. The value of the highest SUVmax distinguished between NSBLs and definite prostate cancer bone metastases, whereby an SUVmax threshold of ≥ 7.2 maximized the Youden’s index. [18F]PSMA-1007 avid NSBLs rarely represent prostate cancer bone metastases. When identified in the absence of definite metastatic disease elsewhere, it is appropriate to classify those with SUVmax

Background Damage to the endothelial glycocalyx is an early indicator of vascular damage and a potential marker of endothelial dysfunction. This study aimed to assess the relationship between markers of glycocalyx damage, endothelial dysfunction, and uraemic toxins in patients with chronic kidney disease. Methods Healthy controls, CKD patients, dialysis patients, and kidney transplant recipients had biochemical markers of glycocalyx damage (syndecan-1 and hyaluronan), endothelial dysfunction (von Willebrand factor; vWF and vascular cell adhesion molecule; VCAM-1), and uraemic toxins (indoxyl sulphate and p-cresyl sulphate) measured. In addition, Sidestream Darkfield imaging was performed using the novel GlycoCheck™ device to measure glycocalyx width by the perfused boundary region (PBR) in the sublingual microcirculation. Results Serum markers of glycocalyx damage were highest in the dialysis group (n = 33), followed by CKD patients (n = 32) and kidney transplant recipients (n = 30) compared to controls (n = 30): hyaluronan: 137 (16-1414), 79 (11–257), 57 (14–218) and 23 (8-116) ng/mL, respectively, p p p = 0.89). Glycocalyx damage correlated with markers of endothelial dysfunction (log-hyaluronan and log-VCAM-1: r = 0.64, p r = 0.48, p Conclusions Levels of biochemical markers of glycocalyx and endothelial cell damage are highest in patients receiving dialysis. Glycocalyx and endothelial damage markers correlated with each other, and with uraemic toxins. Although we could not demonstrate a change in PBR, the biochemical markers suggest that glycocalyx damage is most marked in patients with higher levels of uraemic toxins.

Radical prostatectomy (RP) is a common treatment choice for localized prostate cancer. While there is increasing utilisation of robotic assisted RP in some centres, open RP (ORP) remains well established and commonly performed in many parts of the world. The goals of modern ORP are to remove the prostate en-bloc with negative surgical margins, while minimising blood loss and preserving urinary continence and erectile function. We present a technical review of ORP incorporating contemporary techniques for control of the deep venous complex, additional haemostatic measures, nerve-sparing and vesicourethral reconstruction.

Amyloidosis of the lower genitourinary tract is an extremely rare condition and often mimics urothelial malignancy. In this paper, we report two cases of ureteral and urethral amyloidosis that initially presented as urothelial carcinoma and were successfully treated with laparoscopic nephroureterectomy and trans-urethral resection, respectively. This disease, with its various atypical presentations, presents a diagnostic challenge to urologists. Awareness is important as excision can be curative, and presence of systemic disease must be excluded.

Background Prostate multiparametric magnetic resonance imaging (mpMRI) has become a popular initial investigation of an elevated PSA and is being incorporated into active surveillance protocols. Decisions on prostate cancer investigation and management based solely on a normal mpMRI remains controversial. Histopathological findings of a totally embedded normal mpMRI lobe are rarely described. Methods A retrospective review of the histological findings of negative preoperative mpMRI lobes in men treated by robot assisted laparoscopic radical prostatectomy (RALP). Inclusion criteria included a preoperative low risk mpMRI for both lobes (Prostate Imaging-Reporting and Data System (PIRADS) ≤ 2) or one negative lobe (with a PIRADS 3-5 in the opposite lobe). Results A single normal mpMRI lobe was identified in 1018 men (PIRADS 3-5 group). Both lobes were normal in 179 men (PIRADS ≤ 2 group). Prostate cancer was identified in 47.6% (485/1018) of the normal mpMRI lobe opposite a PIRADS 3-5 lesion, including 13.2% (134/1018) with >0.5 cc of International Society of Urologic Pathologists (ISUP) grade 2, or a higher grade cancer. ISUP grade 4-5 was only identified in 2% (20/1018). Compared to RALP histology of the PIRADS 3-5 mpMRI tumour, a pathological ISUP upgrade in the normal mpMRI lobe was identified in 58/1018 men (5.7%). In the PIRADS ≤ 2 group extraprostatic extension occurred in 19% (34/179) and seminal vesicle invasion (pT3b) in 3.9% (7/179). There was no difference in margin status between the PIRADS 3-5 and ≤2 groups (p = 0.247). Conclusions mpMRI underestimates tumour grade and volume compared to totally embedded histopathological analysis of RALP specimens, although ISUP grade 4-5 cancer is uncommon. Our analysis provides useful insight into the multifocality of prostate cancers, and highlights the utility of systematic biopsy, in addition to targeted biopsies. These results have ramifications for clinical decisions on prostate cancer management based solely on the mpMRI appearance, including active surveillance.

A Man with Fever and Shortness of Breath after Liver Transplantation A 66-year-old man with hypertension, diabetes, hyperlipidemia, obesity, chronic kidney disease, and end-stage liver disease, for...

Objective To evaluate the ability of preoperative multiparametric magnetic resonance imaging (mpMRI) and a gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography (Ga-68-PSMA PET/CT) scan to predict pathological outcomes and also identify a group of men with a 30% risk of microscopic LNM despite a negative preoperative(68)Ga-PSMA PET/CT and this high-risk group would appear suitable for an extended PLND at the time of a radical prostatectomy.

Transrectal (TR) and transperineal (TP) approaches for prostate biopsy have different morbidity profiles. Our institution transitioned to a preference for multiparametric MRI-based triage and TP biopsy since 2014. The aim of this study was to compare clinical, microbiological and health economic outcomes between TR and TP prostate biopsy. A consecutive cohort study considered prostate biopsies over an 11 year period. Hospital presentations across the region within 30 days of biopsy were analysed for details and subsequent outcomes according to biopsy approach. Cost for each encounter (routine and unplanned) were analysed and generalised linear models applied, as well as cost implications for inclusion of mpMRI-based triage and TP biopsy preference. In total, 2048 prostate biopsies were performed. Similar re-presentation rates per occurred for each biopsy approach (90 patients, TR 4.8%, TP 3.8%, p = 0.29), with 23 patients presenting more than once (119 total presentations). Presentations after TR biopsy were more likely to be of infectious aetiology (TR 2.92%, TP 0.26% de novo, p

Androgen deprivation therapy (ADT) is still a mainstay of treatment for advanced prostate cancer. Continuous ADT causes considerable patient morbidity including sexual dysfunction, poor mood and physical capacity, changes in body composition and health-care-related costs. Intermittent ADT has been used as an approach to ADT monotherapy to limit morbidity by enabling cyclical recovery of serum testosterone levels. To date, a number of well-performed randomized controlled trials and meta-analyses have demonstrated statistically insignificant differences in oncological outcomes between intermittent and continuous ADT monotherapy. Sexual outcomes, morbidity profiles and cost-savings favour intermittent therapy in most randomized trials, but the benefit for clinical practice is unclear. Despite the growing body of evidence, the optimal administration regime for ADT has not been clearly established and incorporation of adjunctive upfront treatments such as chemotherapy and novel anti-androgen agents has further hampered progress. Recommendations by authoritative urological and oncological societies regarding the use of intermittent ADT are limited. The potential benefits of reduced morbidity for a particular patient must be considered in light of the possible oncological outcomes. Although the oncological changes associated with intermittent ADT are controversial, intermittent ADT does seem to provide symptomatic benefit in patients compared with continuous ADT. However, careful selection of suitable patients is crucial.

Prospective evidence for the clinical role and efficacy of prostate specific membrane antigen (PSMA) positron emission tomography (PET)/magnetic resonance imaging (MRI) combining MRI characterization and localization of lesions with PET avidity in comparison to conventional imaging is limited. In a prospective clinical trial, we aimed to evaluate the diagnostic yield and therapeutic impact of PSMA PET/MRI in men with biochemical recurrence (BCR) following curative therapy. A single-centre, prospective clinical trial at the Princess Alexandra Hospital recruited 30 patients with BCR. Patients underwent PSMA PET/MRI and concurrent conventional CT chest, abdomen, pelvis and whole-body bone scan. Biopsy was performed when safety possible for histological correlation of identified lesions. Clinical efficacy and impact of PSMA PET findings were evaluated. 30 patients with BCR were recruited (median PSA 0.69 ng/ml). PSMA avid lesions were present in 21 patients (70%). 23 patients were previously treated with definitive surgery, 6 patients received external beam radiotherapy and 1 patient had low dose rate brachytherapy. A total of 8 of 9 lesions biopsied were positive (88.9% histological correlation). PSMA PET/MRI detected local recurrence (p = 0.005) and pelvic lesions (p = 0.06) more accurately than conventional imaging. PSMA PET/MRI may be useful in staging men with biochemical recurrence, especially when PSA is low. Our data demonstrates a high detection rate, especially for locally recurrent disease, and highlights the role of this modality when PSA is low. This modality has the potential to significantly improve prostate cancer detection and may have implications for earlier salvage treatment, avoidance of futile local therapy and change patient management to lead to improved outcomes.

Purpose: To perform a systematic review and meta-analysis and to assess the clinical benefit of prophylactic pelvic drain (PD) placement after robot-assisted laparoscopic prostatectomy (RALP) with ...

Accurate staging of high-risk localised, advanced, and metastatic prostate cancer is becoming increasingly more important in guiding local and systemic treatment. Gallium-68 prostate-specific membrane antigen (PSMA) positron emission tomography (PET) has increasingly been utilised globally to assess the local and metastatic burden of prostate cancer, typically in biochemically recurrent or advanced disease. Following our previous meta-analysis, a high-volume series has been reported highlighting the utility ofTo perform a systematic review and meta-analysis to update reported predictors of positiveWe performed critical reviews of MEDLINE, EMBASE, ScienceDirect, Cochrane Libraries, and Web of Science databases in July 2018 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Quality assessment was performed using Quality Assessment if Diagnostic Accuracy Studies-2 tool. Meta-analyses of proportions were performed using a random-effect model. Summary sensitivity and specificity values were obtained by fitting bivariate hierarchical regression models.A total of 37 articles including 4790 patients were analysed. For patients with biochemical recurrence, positiveGa-68-PSMA PET improves detection of metastases with biochemical recurrence, particularly at low pre-PET PSA levels of0.2ng/ml (33%) and 0.2-0.5ng/ml (45%). Ga-68-PSMA-PET produces favourable sensitivity and specificity profiles on meta-analysis of pooled data. This analysis highlights different anatomic patterns of metastatic spread according to PSMA PET in the primary and biochemically recurrent settings.Gallium-68 prostate-specific membrane antigen positron emission tomography is now an established imaging technique that has been developed in response to inadequacies in standard of care imaging modalities to improve the detection of metastatic disease in prostate cancer, particularly in the setting of disease recurrence. To date, this imaging modality in the setting of primary staging is controversial, given the paucity of data. In light of the growing body of evidence, we summarised the data to date to provide clinicians with an overview of this imaging modality.

Background Prostate biopsy is a standard tool for diagnosing prostate cancer, with more than 4 million procedures performed worldwide each year. Infectious complications and economic burden are reportedly rising with continued use of trans-rectal ultrasound-guided biopsy, despite the transperineal approach being associated with less infectious complications. Objective and methods In this review, the contemporary literature on pathophysiology, epidemiology, risk factors, causative organisms and emerging approaches for prevention of infectious complications are outlined. Results Management of infectious complications after TRUSB has caused significant financial burden on health systems. The most frequent causative agents of infectious complications after prostate biopsy are Gram-negative bacilli are particularly concerning in the era of antibiotic resistance. Increasing resistance to fluoroquinolones and beta-lactam antibiotics has complicated traditional preventive measures. Patient- and procedure-related risk factors, reported by individual studies, can contribute to infectious complications after prostate biopsy. Conclusions Recent literature shows that the transrectal ultrasound-guided prostate biopsy results in higher infectious complication rate than the transperineal prostate biopsy. NAATs, recently introduced technique to detect FQr may detect all antibiotic-resistant rectal microbiota members-included MDRs-although the technique still has limitations and economical burdens. Transient solutions are escalating antibiotic prophylaxis and widening the indications for TPB.

Hematopoietic stem cell transplantation (HSCT) recipients are vulnerable to invasive pneumococcal disease (IPD), with reported IPD rates ranging from 3.81 to 22.5/1000 HSCT. This IPD risk could relate to immunodeficiency, low vaccination uptake, and poor immunogenicity of pneumococcal polysaccharide vaccine (PPV). Literature comparing the clinical effectiveness of pneumococcal conjugate vaccination (PCV) and PPV after HSCT is limited. In this retrospective analysis of HSCT recipients at our center from 2004 to 2015, we evaluated vaccination uptake and compared IPD rates in patients receiving PPV (pre-2010 group) and PCV (post-2010 group). IPD was determined from microbiological results for all HSCT recipients from January 2004 to June 30, 2019. Eight hundred patients had a total of 842 HSCT events, including autologous HSCT (auto-HSCT; n = 562) and allogeneic HSCT (allo-HSCT; n = 280). More than 90% of the HSCT recipients were enrolled, and93% of surviving HSCT recipients completed the vaccination protocol. Fifteen IPD episodes occurred in 13 patients between 2004 and June 30, 2019. Thirteen episodes occurred in the pre-2010 group, even though 9 of 13 (69%) serotyped isolates were covered by PPV. Two episodes occurred in the post-2010 group; neither serotype was covered by PCV. Thus, with PCV introduction, IPD rate was significantly reduced from 38.5/1000 unique HSCTs pre-2010 to 4.0/1000 unique HSCTs post-2010 (P.001). A significant reduction was seen in both auto-HSCTs (from 29.4 to 3.1 /1000 unique auto-HSCTs; P = .011) and allo-HSCTs (from 58.3 to 5.6/1000 unique allo-HSCTs; P = .011). PCV demonstrated superior clinical effectiveness over PPV, highlighting its importance in preventing infectious complications after HSCT. Robust vaccination programs at transplantation centers are needed to optimize vaccination uptake and completion.

68Ga prostate specific membrane antigen PET/CT (68Ga-PSMA PET/CT) may be superior to multiparametric MRI (mpMRI) for localisation of prostate cancer tumour foci, however the concordance and differences between 68Ga-PSMA PET/CT and mpMRI when applied to all biopsied patients and potential benefit in patients with negative mpMRI is unclear. Retrospective analysis of patients undergoing mpMRI, prostate biopsy and 68Ga-PSMA PET/CT over a 3-year period. Diagnostic performance of 68Ga-PSMA PET/CT and mpMRI were assessed using biopsy histopathology for the entire cohort and radical prostatectomy specimen in a subset of patients. Lesion concordance and additional detection of each modality were determined, including in a dedicated cohort of patients with mpMRI PIRADS 2 scans. A total of 144 patients were included in the study. Index lesion/foci detection was similar between 68Ga-PSMA PET/CT and mpMRI (sensitivity 83.1% vs 90.1%; p = 0.267), however lesions missed by mpMRI were larger (1.66 cm3 vs 0.72 cm3; p = 0.034). Lesion detection rates were similar across the biopsy histopathology and radical prostatectomy specimen subset, with a high concordance for index (80.1%) and a moderate concordance for total (67%) lesions between the 2 imaging modalities. The additional detection yield favoured 68Ga-PSMA PET/CT over mpMRI for index (13.5% vs 4.3%) and total (18.2% vs 5.4%) lesions; both modalities missed 2.1% and 12.3% of index and total lesions, respectively. 68Ga-PSMA PET/CT identified 9 of 11 patients with PIRADS 2 mpMRI but subsequently diagnosed with Gleason ≥ 3 + 4 disease. Despite high concordance rates, 68Ga-PSMA PET/CT incrementally improved tumour localisation compared with mpMRI. These results suggest that 68Ga-PSMA PET/CT may have an incremental value to that of mpMRI in the diagnostic process for prostate.

ObjectivesTo investigate the associations of physical activity level with COVID-19 mortality risk across body mass index (BMI) categories, and to determine whether any protective association of a higher physical activity level in individuals with obesity may be explained by favourable levels of cardiometabolic and inflammatory biomarkers.DesignProspective cohort study (baseline data collected between 2006 and 2010). Physical activity level was assessed using the International Physical Activity Questionnaire (high: ≥3000 Metabolic Equivalent of Task (MET)-min/week, moderate: ≥600 MET-min/week, low: not meeting either criteria), and biochemical assays were conducted on blood samples to provide biomarker data.SettingUK Biobank.Main outcome measuresLogistic regressions adjusted for potential confounders were performed to determine the associations of exposure variables with COVID-19 mortality risk. Mortality from COVID-19 was ascertained by death certificates through linkage with National Health Service (NHS) Digital.ResultsWithin the 259 397 included participants, 397 COVID-19 deaths occurred between 16 March 2020 and 27 February 2021. Compared with highly active individuals with a normal BMI (reference group), the ORs (95% CIs) for COVID-19 mortality were 1.61 (0.98 to 2.64) for highly active individuals with obesity, 2.85 (1.78 to 4.57) for lowly active individuals with obesity and 1.94 (1.04 to 3.61) for lowly active individuals with a normal BMI. Of the included biomarkers, neutrophil count and monocyte count were significantly positively associated with COVID-19 mortality risk. In a subanalysis restricted to individuals with obesity, adjusting for these biomarkers attenuated the higher COVID-19 mortality risk in lowly versus highly active individuals with obesity by 10%.ConclusionsThis study provides novel evidence suggesting that a high physical activity level may attenuate the COVID-19 mortality risk associated with obesity. Although the protective association may be partly explained by lower neutrophil and monocyte counts, it still remains largely unexplained by the biomarkers included in this analysis.

PURPOSE We assessed whether sampling of the transitional zone can be spared in patients with exclusively peripheral prostate cancer (PCa)-suspicious multiparametric magnetic resonance imaging (mpMRI) lesions who undergo combined mpMRI targeted (TBx) and systematic prostate biopsies (SBx). MATERIALS AND METHODS Of 1,685 patients who underwent extended SBx including transitional zone sampling and had TBx of ≥1 lesion in the peripheral and/or transitional zone, we selected 863 patients with exclusively peripheral PCa-suspicious lesions and negative transitional zone mpMRI. Clinically significant PCa (csPCa) was defined as Gleason score (GS) ≥3+4. Within the selected cohort we performed a retrospective head-to-head comparison of csPCa detection rates between biopsy protocols: A) combination of peripheral TBx plus extended SBx including transitional zone sampling vs B) peripheral TBx plus SBx without any transitional zone sampling. Analyses were complemented with multivariable logistic regression models (LRMs) in the total cohort for predicting csPCa in SBx transitional zone sampling. RESULTS Compared to the extended protocol (A), omission of systematic transitional zone sampling (B) yielded similar PCa detection for csPCa (48% vs 47%) and GS 3+3 (21% vs 20%). Only 2.0% csPCa was additionally detected with transitional zone SBx sampling (A). LRM confirmed that intraprostatic zonal distribution of mpMRI lesions independently influences csPCa detection rates of transitional zone SBx sampling. CONCLUSIONS A peripheral TBx plus SBx without any transitional zone sampling protocol (B) yields similar csPCa detection rates as the standard extended protocol (A) but may reduce biopsy-related morbidity. This zone-dependent biopsy strategy warrants prospective evaluation to optimize the extent of systematic biopsies in presence of suspicious mpMRI lesions.

Introduction: Intraoperative surgical complications pose significant potential risks to patients. Uncontrolled bleeding during laparoscopic partial nephrectomy is one such event that requires collaboration and communication between surgical team members. We developed and evaluated a multidisciplinary surgical simulation scenario and model of intraoperative hemorrhage during a laparoscopic partial nephrectomy to facilitate the practice of these crucial non-technical skills. Methods: A simulation scenario using a novel, titratable bleeding partial nephrectomy model was developed. The operating room simulation consisted of an intubated mannequin placed in the lateral decubitus position and laparoscopic renal model. The multidisciplinary simulation scenario included anesthesia and urology residents and progressed from bleeding to a pulseless electrical activity arrest. The degree of renal model bleeding was modified based on the progression of the urology resident. After the scenario participants were debriefed and completed a post-simulation survey assessing: 1) their perception of the simulated scenario; and 2) their teaching of non-technical skills in their residency training. Results: The porcine model was successfully reproduced for nine consecutive weeks and functioned well to simulate bleeding from a laparoscopic partial nephrectomy site; the bleeding was able to be titrated based on resident progression and excision of the simulated tumor. All residents stated the scenario was valuable to assess and improve non-technical surgical skills and that their exposure to practice non-technical skills in their existing curriculum could be improved. Conclusions: Simulating an intraoperative bleeding partial nephrectomy, combined with an intraoperative crisis scenario, is a feasible, immersive, and reproducible model and can challenge residents’ non-technical skills.

Introduction: The endothelial glycocalyx on the vascular luminal surface contributes to endothelial health and function. Damage to this layer is indicative of vascular injury, reflected by increased levels of its shed constituents in serum and an increase in the perfused boundary region (PBR) when measured in sublingual capillaries using the GlycoCheck™ device. We aimed to examine the longitudinal effects of kidney transplantation on the glycocalyx by measuring biochemical markers of the glycocalyx and endothelial dysfunction and the PBR. Methods: We recruited healthy controls and stage 5 CKD patients scheduled to undergo a kidney transplant. Investigations were performed before transplant and then 1 and 3 months after transplantation. At each point, blood was collected for hyaluronan, syndecan-1, vascular cell adhesion molecule (VCAM-1), and von Willebrand factor (vWF), and a PBR measurement was performed. Results: Thirty healthy controls and 17 patients undergoing a kidney transplant were recruited (9 cadaveric and 8 live donation; 12 on dialysis and 5 pre-emptive). Before transplant, transplant recipients had greater evidence of glycocalyx damage than controls. After transplant, PBR improved from median 2.22 (range 1.29–2.73) to 1.98 (1.65–2.25) µm, p = 0.024, and syndecan-1 levels decreased from 98 (40–529) to 36 (20–328) ng/mL, p < 0.001. Similarly, VCAM-1 fell from 1,479 (751–2,428) at baseline to 823 (516–1,674) ng/mL, p < 0.001, and vWF reduced from 3,114 (1,549–5,197) to 2,007 (1,503–3,542) mIU/mL, p = 0.002. Serum levels of hyaluronan remained unchanged. Conclusion: The combination of reduced PBR and syndecan-1 following transplant suggests that transplantation may improve glycocalyx stability at 3 months after transplant.

Social disparity is a major impediment to optimal health outcomes after kidney transplantation. In this study, we aimed to define the association between socio-economic status (SES) disparities and patient-relevant outcomes after kidney allograft failure. Using data from the Australia and New Zealand Dialysis and Transplant registry, we included patients with failed first-kidney allografts in Australia between 2005 and 2017. The association between residential postcode-derived SES in quintiles (quintile 1-most disadvantaged areas, quintile 5-most advantaged areas) with uptake of home dialysis (peritoneal or home haemodialysis) within the first 12-months post-allograft failure, repeat transplantation and death on dialysis were examined using competing-risk analysis. Of 2175 patients who had experienced first allograft failure, 417(19%) and 505(23%) patients were of SES quintiles 1 and 5, respectively. Compared to patients of quintile 5, quintile 1 patients were less likely to receive repeat transplants (adjusted subdistributional hazard ratio [SHR] 0.70,95%CI 0.55–0.89) and were more likely to die on dialysis (1.37 [1.04–1.81]), but there was no association with the uptake of home dialysis (1.02 [0.77–1.35]). Low SES may have a negative effect on outcomes post-allograft failure and further research is required into how best to mitigate this. However, small-scale variation within SES cannot be accounted for in this study.

To characterize national clinical practice trends in the treatment of prostate cancer (PCa) in Australia.Population-level data were extracted from existing Medicare Benefits Schedule data for radical prostatectomy (RP) and brachytherapy (2002-2016), as well as external beam radiotherapy (EBRT; 2012-2016). Treatment rates were calculated relative to whole and PCa populations among privately treated patients. Overall age-related and geographical trends were analysed.The use of RP and low-dose-rate (LDR) brachytherapy increased between 2002 and 2009, but subsequently decreased to 124 and 6.9 per 100 000 men, respectively, in 2016. More dramatic decreases were observed for men aged65 years. From 2012, rates of RP (15% drop) and LDR brachytherapy (58% drop) decreased, while the use of EBRT remained steady, falling by 5% to 42 per 100 000 men in 2016. Overall treatment increased in the age group 75-84 years, with the rate of RP increasing by 108%.National claims data indicate there has been a reduction in PCa treatment since 2009, which is mostly attributable to a reduction in the treatment of younger patients and reduced use of brachytherapy. RP is most commonly used and its use is rising in men aged65 years.

BACKGROUND Guidelines recommend nephron sparing surgery where possible for patients with T1 renal tumours. The trends of nephron sparing surgery outside the USA are limited, particularly since the introduction of robotic-assisted partial nephrectomy (RAPN). The aim of this study was to describe contemporary surgical management patterns of renal tumours in Australia according to Medicare claims data. METHODS Claims data according to the Medicare Benefits Schedule on surgical management of renal tumours in adult Australians between January 2000 and December 2016 was collated. Analysis of absolute number, population-adjusted rate and renal cancer-adjusted rate of interventions according to age and gender were performed, as well as proportion of RAPN. RESULTS Between 2000 and 2016, the rate of partial nephrectomy (PN) increased while radical nephrectomy (RN) remained stable (PN: 0.87-4.16, RN: 6.52-6.70 per 100 000 population). Since 2015, PN has become more common than RN in patients aged 25 to 44 years (0.98 versus 0.95 procedures per 100 000 population). Renal cancer-adjusted rate exhibited a trend towards increasing utilization of PN and reduced RN across all age groups. An increase in overall surgical treatment was observed (25%-41%), mainly due to increased treatment of patients older than 75 years. The proportion of RAPN was seen to rapidly increase (4.7% in 2010 to 58% in 2016). CONCLUSIONS Treatment utilization for renal masses has markedly changed in Australia according to Medicare claims. PN is increasingly replacing RN in younger patients, and older patients are receiving more surgical treatment. The impact of increased RAPN utilization is yet to be determined.

Multiparametric magnetic resonance imaging (mpMRI) improves clinically significant prostate cancer (csPCa) detection by facilitating targeted biopsy (cognitive, fusion technology, or in-gantry MRI guidance) and reducing negative biopsies. This study sought to describe the feasibility of introducing an mpMRI-based triage pathway, including diagnostic performance, applicability to training, and cost analysis. An observational retrospective cohort study of consecutive patients attending a large public tertiary referral training hospital who underwent mpMRI for suspicion of prostate cancer was considered. Standard clinical, MRI-related, histopathological, and financial parameters were collected for analysis of biopsy avoidance, diagnostic accuracy of biopsy approach, and operator (consultant and resident/registrar) and logistical (including financial) feasibility. 653 men underwent mpMRI, of which 344 underwent prostate biopsy resulting in a 47% biopsy avoidance rate. Overall, 240 (69.8%) patients were diagnosed with PCa, of which 208 (60.5%) were clinically significant, with higher rates of csPCa observed for higher PIRADS scores. In patients who underwent both systematic and targeted biopsy (stTPB), targeted cores detected csPCa in 12.7% and 16.6% in more men than systematic cores in PIRADS 5 and 4, respectively, whereas systematic cores detected csPCa in 5% and 3.2% of patients, where targeted cores did not. A high standard of performance was maintained across the study period and the approach was shown to be cost effective. Introdution of an mpMRI-based triage system into a large public tertiary teaching hospital is feasible, cost effective and leads to high rates of prostate cancer diagnosis while reducing unnecessary biopsies and detection of insignificant PCa.

Background: Arthrodesis of the first metatarsophalangeal (MTP) joint has been shown to be effective in alleviating pain and correcting deformity in hallux rigidus. However, outcomes in specific sports and physical activities remain unclear. The aim of this study was to assess sports and physical activities in young patients following first MTP joint arthrodesis and to compare these results with clinical outcomes. Methods: Patients between ages 18 and 55 years who underwent MTP arthrodesis were identified by review of a prospective registry. Fifty of 73 eligible patients (68%) were reached for follow-up at a mean of 5.1 (range, 2.2-10.2) years with a mean age at surgery of 49.7 (range, 23-55) years. Physical activity was evaluated with a previously developed sports-specific, patient-administered questionnaire. Clinical outcomes were evaluated with the Foot and Ankle Outcome Score (FAOS). Results: Patients participated in 22 different sports and physical activities. The most common were walking, biking, weightlifting, swimming, running, and golf. Compared to preoperatively, patients rated 27.4% of activities as less difficult, 51.2% as the same, and 21.4% as more difficult. Patients returned to 44.6% of preoperative physical activities in less than 6 months and reached their maximal level of participation in 88.6% of physical activities. Ninety-six percent of patients (48/50) were satisfied with the procedure regarding return to sports and physical activities. Improvements in the FAOS Symptoms subscore were associated with increased postoperative running and walking duration, and improvements in FAOS Pain subscores were associated with greater patient satisfaction. Conclusion: Patients were able to participate in a wide variety of sports and physical activities postoperatively. Some patients reported increased difficulty, but were nonetheless satisfied with the procedure regarding physical activity participation. These findings suggest that first MTP joint arthrodesis is a reasonable option in young, active patients, and may be used to guide postoperative expectations. Level of Evidence: Level IV, retrospective case series.

Aim Levels of plasma markers of myocardial fibrosis (galectin-3), stretch (B-type natriuretic peptide (BNP)) and injury (troponin T (TnT)) may be affected by haemodialysis and residual renal function (RRF) in addition to cardiac pathology. We aimed to determine the association of RRF, urine output and haemodialysis itself on clinically important cardiac biomarkers in haemodialysis patients. Methods Adult haemodialysis patients underwent venesection pre- and post- haemodialysis followed by echocardiography and inter-dialytic urine collection to calculate RRF (mL/minute/1.73m2) and urine output (mL/day). Galectin-3, BNP-32, NT-ProBNP and high-sensitivity TnT were measured and levels compared across tertiles of echocardiographic parameters, RRF and urine output using the non-parametric test for trend across ordered groups. Results Twenty-three patients (17 male) with mean age 67.7±13.8 years and median (interquartile range, IQR) dialysis duration 13.6 (9.8-19.1) months participated. Galectin-3 was substantially lower following haemodialysis: 55ng/mL (47-70) versus 23ng/mL (19-27, p

Background: Different nomograms exist for the preoperative prediction of pelvic lymph-node metastatic disease in individual patients with prostate cancer (PCa). These nomograms do not incorporate modern imaging techniques such as prostate-specific membrane antigen (PSMA) positron emission tomography (PET). Objective: To determine the predictive performance of the Briganti 2017, Memorial Sloan Kettering Cancer Center (MSKCC), and Briganti 2019 nomograms with the addition of PSMA-PET in an international, multicenter, present-day cohort of patients undergoing robot-assisted radical prostatectomy (RARP) and extended pelvic lymph-node dissection (ePLND) for localized PCa. Design, setting, and participants: All 757 eligible patients who underwent a PSMA-PET prior to RARP and ePLND in three reference centers for PCa surgery between January 2016 and November 2020 were included. Outcome measurements and statistical analysis: Performance of the three nomograms was assessed using the receiver operating characteristic curve–derived area under the curve (AUC), calibration plots, and decision curve analyses. Subsequently, recalibration and addition of PSMA-PET to the nomograms were performed. Results and limitations: Overall, 186/757 patients (25%) had pelvic lymph-node metastatic (pN1) disease on histopathological examination. AUCs of the Briganti 2017, MSKCC, and Briganti 2019 nomograms were 0.70 (95% confidence interval [95% CI]: 0.64–0.77), 0.71 (95% CI: 0.65–0.77), and 0.76 (95% CI: 0.71–0.82), respectively. PSMA-PET findings showed a significant association with pN1 disease when added to the nomograms (p < 0.001). Addition of PSMA-PET substantially improved the discriminative ability of the models yielding cross-validated AUCs of 0.76 (95% CI: 0.70–0.82), 0.77 (95% CI: 0.72–0.83), and 0.82 (95% CI: 0.76–0.87), respectively. In decision curve analyses, the addition of PSMA-PET to the three nomograms resulted in increased net benefits. Conclusions: The addition of PSMA-PET to the previously developed nomograms showed substantially improved predictive performance, which suggests that PSMA-PET is a likely future candidate for a modern predictive nomogram. Patient summary: Different tools have been developed to individualize the prediction of prostate cancer spread to lymph nodes before surgery. We found that the inclusion of modern imaging (prostate-specific membrane antigen positron emission tomography) improved substantially the overall performance of these prediction tools.

BACKGROUND: Commencing hemodialysis (HD) with an arteriovenous access is associated with superior patient outcomes compared with a catheter, but the majority of patients in Australia and New Zealand initiate HD with a central venous catheter. This study examined patient and center factors associated with arteriovenous fistula/graft access use at HD commencement. METHODS: We included all adult patients starting chronic HD in Australia and New Zealand between 2004 and 2015. Access type at HD initiation was analyzed using logistic regression. Patient-level factors included sex, age, race, body mass index (BMI), smoking status, primary kidney disease, late nephrologist referral, comorbidities, and prior RRT. Center-level factors included size; transplant capability; home HD proportion; incident peritoneal dialysis (average number of patients commencing RRT with peritoneal dialysis per year); mean weekly HD hours; average blood flow; and achievement of phosphate, hemoglobin, and weekly Kt/V targets. The study included 27,123 patients from 61 centers. RESULTS: Arteriovenous access use at HD commencement varied four-fold from 15% to 62% (median 39%) across centers. Incident arteriovenous access use was more likely in patients aged 51–72 years, males, and patients with a BMI of >25 kg/m(2) and polycystic kidney disease; but use was less likely in patients with a BMI of

Invasive candidiasis is one of the common infections in solid organ transplant recipients. Guidelines recommend echinocandins or liposomal amphotericin with consideration of flucytosine (5-fluorocytosine; 5-FC) as synergistic therapy for treatment of select deep-seated Candida infections, including complex endovascular infections. Flucytosine undergoes extensive renal elimination; however, optimal dosing in patients with renal impairment, or those requiring renal replacement therapy (RRT), is not well-established. We describe a case of a 60-year old female who underwent orthotopic heart transplant complicated by Candida parapsilosis complex fungemia with mediastinitis and development of end-stage renal disease requiring RRT. Flucytosine therapeutic drug monitoring was performed on continuous veno-venous hemofiltration (CVVH) and intermittent hemodialysis (iHD) to guide appropriate dosing. Our results support 5-FC doses of 25 mg/kg daily while undergoing CVVH with a low fluid replacement rate and 21 mg/kg post-iHD or 17 mg/kg daily while receiving thrice weekly iHD.

PSMA PET is more accurate than conventional imaging (CT/bone scan) for staging of intermediate- or high-risk prostate cancer (PCa), but 5–10% of primary tumours have low PSMA ligand uptake. FDG PET has been used to further define disease extent in end-stage castrate-resistant PCa and may be beneficial earlier in the disease course for more accurate staging. The objective of this study was to review the available evidence for patients undergoing both FDG and PSMA PET for PCa staging at initial diagnosis and in recurrent disease. A systematic literature review was performed for studies with direct, intraindividual comparison of PSMA and FDG PET for staging of PCa. Assessment for radioligand therapy eligibility was not considered. Risk of bias was assessed. 543 citations were screened and assessed. 13 case reports, three retrospective studies, and one prospective study were included. FDG after PSMA PET improved the detection of metastases from 65% to 73% in high-risk early castration-resistant PCa with negative conventional imaging (M0). Positive FDG PET was found in 17% of men with negative PSMA PET for postprostatectomy biochemical recurrence. Gleason score ≥8 and higher PSA levels predicted FDG-avid metastases in BCR and primary staging. Variant histology (ductal and neuroendocrine) was common in case reports, resulting in PSMA-negative FDG-positive imaging for 3 patients. Dual-tracer PET for PCa may assist in characterising high-risk disease during primary staging and restaging. Further studies are required to determine the additive benefit of FDG PET and if the FDG-positive phenotype may indicate a poorer prognosis.

Category: Other Introduction/Purpose: Cases of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus (COVID-19) first emerged in Wuhan, China, in December 2019. Since then, the virus has spread globally at a rapid pace. The first case in New York City was reported on March 1, 2020, and the World Health Organization (WHO) declared a pandemic on March 11, 2020. New York City rapidly became the epicenter of the pandemic, with hospitals across the city making a number of changes to accommodate the influx of COVID-19 patients. Here, we describe our experience in adapting to the COVID-19 pandemic as a department consisting of 10 foot and ankle fellowship-trained surgeons with up to 28 years of individual experience in an academic orthopedic hospital. Methods: Information was obtained from direct interviews with surgeons in the Foot and Ankle Service and from our institution’s intranet. Additional information was obtained by viewing twice-weekly livestreams from March 27th, 2020 to May 1st, 2020 held by the Surgeon-In-Chief, which detailed hospital-wide policies and initiatives being implemented in the wake of the COVID-19 pandemic. Results: On March 17, 2020, all elective surgeries were suspended at our institution, and a list of essential procedures was established. In-person clinical visits were limited to new patients being evaluated for essential procedures and first postoperative visits for returning patients, with all patients receiving pre-visit and on-site screening for COVID-19. All other new patient and follow-up appointments were conducted via telehealth visits. Much of our main hospital was repurposed to accept transfers of both COVID-negative and COVID-positive patients. A postanesthesia care unit and a floor of 9 operating rooms were repurposed as negative-pressure rooms for the care of critical COVID-positive patients on ventilators. An Orthopedic Triage Center (OTC) was established to relieve the patient load in the emergency departments of other hospitals in the city. Conclusion: By changing the way we delivered foot and ankle care and repurposing the roles of our employees and our institution, we have adapted strategies to continue delivering care to our patients. As we transition toward a ‘new normal,’ our goals are to gradually progress toward normal operations while keeping our patients and employees safe. With these gradual steps, we hope to emerge from this pandemic stronger and ready to adapt to the ever-changing needs of our community.

Background Spontaneous renal fornix rupture (SRFR) causing urinoma is an uncommon but serious condition in pregnancy. Limited information is available to describe the natural history and outcomes to guide appropriate treatment. The aim of this study was to determine the natural history and outcomes of SRFR to determine appropriate management recommendations. Methods A systematic review of literature databases was performed, using the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) checklist from 1950 – April 2020. Inclusion criteria included any urinary extravasation from the kidney or ureter during pregnancy, or in the 8 weeks following delivery, confirmed via imaging or surgery. Haematomas and non-confirmed cases were excluded. Results A total of 1579 records were originally identified, of which 39 case reports were appropriate for inclusion. SRFR was most commonly reported during the first pregnancy (72%), 19/30 during the third trimester and 9 in the post-natal period. All patients presented with pain, with haematuria positive on urine dipstick in only 36% of 26 reported cases. Ultrasound was the most frequently used imaging modality, resulting in a diagnosis in 42% of cases. All cases reported on treatment procedures including ureteric stents (46%), percutaneous drain (15%), conservative management (15%), nephrostomy (13%) and ureteral catherization (10%). Long term urological outcomes were positive, however women suffering SRFR were significantly more likely to undergo pre-term labour. Conclusion While selected cases may be successfully managed conservatively, urinary diversion, through ureteric stents, should be considered the management of choice in these individuals. Clinicians should be mindful of an increased risk of premature delivery and its’ associated negative fetal outcomes.

Successful solid organ transplantation reflects meticulous attention to the details of immunosuppression, balancing risks for graft rejection against risks for infection. The “net state of immune suppression” is a conceptual framework of all factors contributing to infectious risk. Assays that measure immune function in the immunosuppressed transplant recipient relative to infectious risk and allograft function are lacking. The best measures of integrated immune function may be quantitative viral loads to assess the individual’s ability to control latent viral infections. Few studies address adjustment of immunosuppression during active infections; thus, confronted with infection in solid organ recipients, the management of immunosuppression is based largely on clinical experience. This review examines known measures of immune function and the immunologic effects of common immunosuppressive drugs and available studies reporting modification of drug regimens for specific infections. These data provide a conceptual framework for the management of immunosuppression during infection in organ recipients.

Background Malnutrition is common in patients with chronic kidney disease (CKD) on dialysis. Oral protein-based nutritional supplements are often provided to patients whose oral intake is otherwise insufficient to meet their energy and protein needs. Evidence for the effectiveness of oral protein-based nutritional supplements in this population is limited. Objectives The aims of this review were to determine the benefits and harms of using oral protein-based nutritional supplements to improve the nutritional state of patients with CKD requiring dialysis. Search methods We searched the Cochrane Kidney and Transplant Register of Studies up to 12 December 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Selection criteria Randomised controlled trials (RCTs) of patients with CKD requiring dialysis that compared oral protein-based nutritional supplements to no oral protein-based nutritional supplements or placebo. Data collection and analysis Two authors independently assessed studies for eligibility, risk of bias, and extracted data from individual studies. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference and 95% CI for continuous outcomes. Main results Twenty-two studies (1278 participants) were included in this review. All participants were adults on maintenance dialysis of whom 79% were on haemodialysis (HD) and 21% peritoneal dialysis. The follow-up period ranged from one to 12 months. The majority of studies were at unclear risk of selection, performance, and reporting bias. The detection bias was high for self-reported outcomes. Oral protein-based nutritional supplements probably lead to a higher mean change in serum albumin compared to the control group (16 studies, 790 participants: MD 0.19 g/dL, 95% CI 0.05 to 0.33; moderate certainty evidence), although there was considerable heterogeneity in the combined analysis (I2 = 84%). The increase was more evident in HD participants (10 studies, 526 participants: MD 0.28 g/dL, 95% CI 0.11 to 0.46; P = 0.001 for overall effect) and malnourished participants (8 studies, 405 participants: MD 0.31 g/dL, 95% CI 0.10 to 0.52, P = 0.003 for overall effect). Oral protein-based nutritional supplements also probably leads to a higher mean serum albumin at the end of the intervention (14 studies, 715 participants: MD 0.14 g/dL, 95% CI 0 to 0.27; moderate certainty evidence), however heterogeneity was again high (I2 = 80%). Again the increase was more evident in HD participants (9 studies, 498 participants: MD 0.21 g/dL, 95% CI 0.03 to 0.38; P = 0.02 for overall effect) and malnourished participants (7 studies, 377 participants: MD 0.25 g/dL, 95% CI 0.02 to 0.47; P = 0.03 for overall effect). Compared to placebo or no supplement, low certainty evidence showed oral protein-based nutritional supplements may result in a higher serum prealbumin (4 studies, 225 participants: MD 2.81 mg/dL, 95% CI 2.19 to 3.43), and mid-arm muscle circumference (4 studies, 216 participants: MD 1.33 cm, 95% CI 0.24 to 2.43) at the end of the intervention. Compared to placebo or no supplement, oral protein-based nutritional supplements may make little or no difference to weight (8 studies, 365 participants: MD 2.83 kg, 95% CI -0.43 to 6.09; low certainty evidence), body mass index (9 studies, 368 participants: MD -0.04 kg/m2, 95% CI -0.74 to 0.66; moderate certainty evidence) and lean mass (5 studies, 189 participants: MD 1.27 kg, 95% CI -1.61 to 4.51; low certainty evidence). Due to very low quality of evidence, it is uncertain whether oral protein-based nutritional supplements affect triceps skinfold thickness, mid-arm circumference, C-reactive protein, Interleukin 6, serum potassium, or serum phosphate. There may be little or no difference in the risk of developing gastrointestinal intolerance between participants who received oral protein-based nutritional supplements compared with placebo or no supplement (6 studies, 426 participants: RR 2.81, 95% CI 0.58 to 13.65, low certainty evidence). It was not possible to draw conclusions about cost or quality of life, and deaths were not reported as a study outcome in any of the included studies. Authors' conclusions Overall, it is likely that oral protein-based nutritional supplements increase both mean change in serum albumin and serum albumin at end of intervention and may improve serum prealbumin and mid-arm muscle circumference. The improvement in serum albumin was more evident in haemodialysis and malnourished participants. However, it remains uncertain whether these results translate to improvement in nutritional status and clinically relevant outcomes such as death. Large well-designed RCTs in this population are required.

Objective To provide a clinically relevant outline of various current precision medicine principles and available evidence on the application and potential for a precision medicine approach in prostate cancer.Methods Narrative review of the current literature in the field.Conclusion Precision medicine is the concept of individualising patient management based on specific tumour characteristics and biology, rather than traditional histological subtypes. The overall aim is to personalise management to individual patients, to provide the right cancer treatment, to the right patient, at the right time. While the approach aims to improve clinical outcomes, decrease morbidity and improve survival in men with advanced prostate cancer, its clinical application is in its infancy. It does however show great promise in this and other cancers, and will continue to be an area of active research and clinical investigation.

AIM: To describe national surgical patterns of prostate cancer (PCa) care considering radical prostatectomy with or without pelvic lymphadenectomy and consideration of robotic-assisted techniques. METHODS: Retrospective analysis of publicly accessible Medicare claims data was performed for the period 2001-2016 and included patients undergoing radical prostatectomy with or without pelvic lymphadenectomy relative to total and PCa-specific populations among men aged 45-84 years. Proportion of cases performed robotically was considered. RESULTS: Total procedures performed increased from 2001, peaked in 2009 and subsequently decreased until 2016. Since 2009, the age-specific rate of surgery in men aged 75-84 increased by 2.3-fold, whereas the rates for men aged 55-64 and 45-54 reduced by 44% and 55%, respectively. Rates of concurrent pelvic lymphadenectomy fell until 2009 with subsequent stabilization (ratio 1.05-1.14) through to 2016. Significant regional practice patterns were observed, as was an increasing trend toward a robotic-assisted laparoscopic approach, comprising more than 80% of radical prostatectomies in 2016. CONCLUSION: Since the peak in 2009, radical prostatectomy is performed less in men

Importance Methicillin-resistantStaphylococcus aureus(MRSA) bacteremia is associated with mortality of more than 20%. Combining standard therapy with a β-lactam antibiotic has been associated with reduced mortality, although adequately powered randomized clinical trials of this intervention have not been conducted. Objective To determine whether combining an antistaphylococcal β-lactam with standard therapy is more effective than standard therapy alone in patients with MRSA bacteremia. Design, Setting, and Participants Open-label, randomized clinical trial conducted at 27 hospital sites in 4 countries from August 2015 to July 2018 among 352 hospitalized adults with MRSA bacteremia. Follow-up was complete on October 23, 2018. Interventions Participants were randomized to standard therapy (intravenous vancomycin or daptomycin) plus an antistaphylococcal β-lactam (intravenous flucloxacillin, cloxacillin, or cefazolin) (n = 174) or standard therapy alone (n = 178). Total duration of therapy was determined by treating clinicians and the β-lactam was administered for 7 days. Main Outcomes and Measures The primary end point was a 90-day composite of mortality, persistent bacteremia at day 5, microbiological relapse, and microbiological treatment failure. Secondary outcomes included mortality at days 14, 42, and 90; persistent bacteremia at days 2 and 5; acute kidney injury (AKI); microbiological relapse; microbiological treatment failure; and duration of intravenous antibiotics. Results The data and safety monitoring board recommended early termination of the study prior to enrollment of 440 patients because of safety. Among 352 patients randomized (mean age, 62.2 [SD, 17.7] years; 121 women [34.4%]), 345 (98%) completed the trial. The primary end point was met by 59 (35%) with combination therapy and 68 (39%) with standard therapy (absolute difference, −4.2%; 95% CI, −14.3% to 6.0%). Seven of 9 prespecified secondary end points showed no significant difference. For the combination therapy vs standard therapy groups, all-cause 90-day mortality occurred in 35 (21%) vs 28 (16%) (difference, 4.5%; 95% CI, −3.7% to 12.7%); persistent bacteremia at day 5 was observed in 19 of 166 (11%) vs 35 of 172 (20%) (difference, −8.9%; 95% CI, −16.6% to −1.2%); and, excluding patients receiving dialysis at baseline, AKI occurred in 34 of 145 (23%) vs 9 of 145 (6%) (difference, 17.2%; 95% CI, 9.3%-25.2%). Conclusions and Relevance Among patients with MRSA bacteremia, addition of an antistaphylococcal β-lactam to standard antibiotic therapy with vancomycin or daptomycin did not result in significant improvement in the primary composite end point of mortality, persistent bacteremia, relapse, or treatment failure. Early trial termination for safety concerns and the possibility that the study was underpowered to detect clinically important differences in favor of the intervention should be considered when interpreting the findings. Trial Registration ClinicalTrials.gov Identifier:NCT02365493

Background In the era of organ shortage, home hemodialysis (HHD) has been identified as the possible preferential bridge to kidney transplantation. Data are conflicting regarding the comparability of HHD and transplantation outcomes. This study aimed to compare patient and treatment survival between HHD patients and kidney transplant recipients. Methods The Australia and New Zealand Dialysis and Transplant Registry was used to include incident HHD patients on Day 90 after initiation of kidney replacement therapy and first kidney-only transplant recipients in Australia and New Zealand from 1997 to 2017. Survival times were analyzed using the Kaplan–Meier product-limit method comparing HHD patients with subtypes of kidney transplant recipients using the log-rank test. Adjusted analyses were performed with multivariable Cox proportional hazards regression models for time to all-cause mortality. Time-to-treatment failure or death was assessed as a composite secondary outcome. Results The study compared 1411 HHD patients with 4960 living donor (LD) recipients, 6019 standard criteria donor (SCD) recipients and 2427 expanded criteria donor (ECD) recipients. While LD and SCD recipients had reduced risks of mortality compared with HHD patients [LD adjusted hazard ratio (HR) = 0.57, 95% confidence interval (CI) 0.46–0.71; SCD HR = 0.65 95% CI 0.52–0.79], the risk of mortality was comparable between ECD recipients and HHD patients (HR = 0.90, 95% CI 0.73–1.12). LD, SCD and ECD kidney recipients each experienced superior time-to-treatment failure or death compared with HHD patients. Conclusions This large registry study showed that kidney transplant offers a survival benefit compared with HHD but that this advantage is not significant for ECD recipients.

© 2020, Springer-Verlag GmbH Germany, part of Springer Nature. Purpose: Prostate-specific membrane antigen (PSMA) positron emission tomography (PSMA-PET) improves prostate cancer staging. Intraprostatic PSMA intensity may predict clinically relevant oncological outcomes. The aim of this study was to investigate the relationship between intraprostatic PSMA intensity and adverse pathology outcomes, including biochemical progression-free survival (PFS) after radical prostatectomy. Methods: This is a cohort study of 71 patients with MRI-guided, biopsy-proven prostate cancer and pre-operative 68Ga-PSMA-11 PET/CT prior to radical prostatectomy (RP). Intraprostatic PSMA intensity was correlated to adverse pathology outcomes (Gleason score and upgrading from biopsy, pathological stage) and PFS using multivariate statistical analysis. Results: 68Ga-PSMA-11 PET/CT intensity in vivo predicted all of Gleason score on RP, upgrading from biopsy to RP histopathology, pathological stage, positive surgical margins and PFS. 74.6% (53/71) of patients were free from progression at a median follow-up of 19.5 months (0.4–48 months). Predictive accuracy was particularly enhanced by PSMA among patients with biopsy Gleason score ≤ 3 + 4 (n = 39) as the most significant predictor of PFS according to Cox-proportional hazards regression. Cox-regression adjusted survival analysis predicted a 5.48-fold increase in hazard for Gleason score ≤ 3 + 4 patients with high (SUVmax > 8) compared with low (SUVmax < 8) PSMA intensity. Conclusion: Intraprostatic 68Ga-PSMA-11 intensity is prognostic and may be a valuable new biomarker in localised prostate cancer, especially in men with biopsy-proven Gleason 3 + 4 disease considering an initial approach of active surveillance or focal therapy.

Objectives: To examine the association between type 2 diabetes mellitus, with and without diabetic nephropathy, and cardiovascular disease-related mortality in dialysis-dependent patients with end-stage kidney disease (ESKD); to determine whether this association is affected by the age of the patient.Design, setting, participants: Prospective population cohort analysis of Australia and New Zealand Dialysis and Transplant Registry data for all patients with incident ESKD who commenced dialysis in Australia or New Zealand during 1980-2014.Outcome measures: Primary outcome: cardiovascular diseaserelated mortality; secondary outcome: all-cause mortality.Results: Of 56 552 patients followed for a median 2.5 years (total, 193 549 person-years), 15 829 (28.0%) had type 2 diabetes and diabetic nephropathy; 4993 (8.8%) had type 2 diabetes and non-diabetic nephropathy. Cardiovascular diseaserelated mortality during the first 10 years of dialysis was significantly higher for patients with diabetes/diabetic nephropathy (277 deaths per 1000 patients; 95% CI, 270-284) or diabetes/non-diabetic nephropathy (220 deaths per 1000 patients; 95% CI, 208-231) than for patients without type 2 diabetes (136 deaths per 1000 patients; 95% CI, 133-140). The risk of cardiovascular disease-related mortality was greater for patients with diabetes/diabetic nephropathy (adjusted hazard ratio [aHR], 1.63; 95% CI, 1.56-1.72) or diabetes/non-diabetic nephropathy (aHR, 1.31; 95% CI, 1.23-1.41) than for patients without diabetes. The excess risk associated with having diabetes was greater for younger than for older patients.Conclusions: Mortality risk is higher for patients with incident ESKD commencing dialysis who also have type 2 diabetes than for patients without diabetes, particularly among patients under 50 years of age, and the risk was more pronounced in patients for whom ESKD was attributed to diabetic nephropathy.

Positron emission tomography (PET) for prostate-specific membrane antigen (PSMA) represents a promising method for prostate cancer diagnosis and staging. Comparisons of PSMA-based tumour characterisation to multiparametric MRI (mpMRI) are limited, hence this study sought to compare the diagnostic accuracy of 68Ga-PSMA PET/CT to mpMRI against radical prostatectomy (RP) whole gland histopathology. A retrospective cohort study of consecutive patients who underwent pre-operative mpMRI and 68Ga-PSMA PET/CT followed by a RP was performed. Standard clinical parameters were collected. “Per patient” and “per lesion” analyses for image-based detection according to RP histopathology were described using sensitivity, specificity and other measures of diagnostic accuracy. Fifty-eight patients (median age 65.5 years, median PSA 7.35 ng/mL) underwent RP, resulting in a high-risk cohort (≥pT3 69%). Sensitivities for identification of index lesion, bilateral and multifocal disease were 90%, 21%, 19% for mpMRI and 93%, 42%, 34% for 68Ga-PSMA PET/CT. Histology analyses revealed 88 cancer foci of Gleason grades 3 + 3 (4%), 3 + 4 (64%), 4 + 3 (19%), 4 + 4 (3%) and ≥ 4 + 5 (10%), of which 68Ga-PSMA PET/CT correctly detected more foci (78%, AUC 0.817) than mpMRI (69%, AUC 0.729). 68Ga-PSMA PET/CT may better reflect RP histopathology compared to mpMRI when considering multifocal and bilateral disease. These findings may influence surgical planning, targeted biopsy and focal therapy strategies and require further research.

Background: Benign prostatic hyperplasia (BPH) is the most common benign tumour in men. Although men with BPH often need medical or surgical management from a urologist at some point throughout the timeline of their disease, most men are initially assessed and managed by a general practitioner (GP) in the primary healthcare setting. Objectives: The aim of this article is to highlight the principles of the pathogenesis, presentation, assessment and management of BPH in a primary care setting. Discussion: Between 2009 and 2011, BPH was managed by GPs at approximately 228,000 general practice visits per annum in Australia. Several changes in pharmaceutical agents and surgical intervention have occurred over the past decade. As a result, it is imperative that GPs remain up to date with assessment and management of BPH, are aware of new therapies and understand when to refer to a urologist.

Aim The Kidney Disease Improving Global Outcomes (KDIGO) guideline recommends the incorporation of a new risk calculator that quantifies the end stage kidney disease (ESKD) risk based on a composite profile of risk factors in living kidney donor candidates (LKDCs). We compared the ESKD risk estimates in previously declined versus accepted LKDCs to evaluate the predictive capacity and potential impact of this tool. Methods Baseline 15-year and lifetime ESKD risk estimates without donation were calculated using the risk calculator for LKDCs assessed from two centres between 2007 and 2015. LKDC suitability based on the proposed KDIGO and the existing Caring for Australasians with Renal Impairment (KHA-CARI) national guidelines was compared. Results Median 15-year ESKD risk was 0.14% (IQR 0.09-0.31%) in declined LKDCs (n = 59) versus 0.10% (0.07-0.14%) in accepted LKDCs (n = 89) (P 1%. This risk calculator appears to complement but not replace clinical evaluation.

Objective: The objective of this article is to conduct a contemporary literature review on Wunderlich syndrome, or spontaneous renal haemorrhage (SRH), among pregnant women to describe contemporary aetiology, investigations and management patterns. Methods: A systematic review of MEDLINE and CENTRAL in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed. All articles, including case reports and case series on SRH published from 2000 to 2016, were included. Full-text manuscripts describing SRH among pregnant women were reviewed for clinical parameters, which were collated and analysed. Results: Twenty cases of SRH in pregnant women were identified. The median age and gestation were 32.1 years and 26.5 weeks, respectively, with SRH most commonly occurring in the third trimester (nine patients; 45%) and due to renal neoplasm, specifically angiomyolipoma (AML; 12 patients; 60%), followed by renal artery aneurysm (RAA; five patients; 25%). Surgical intervention (55%) was most commonly used for acute SRH. Foetal demise was not uncommon (15%). Conclusions: SRH in pregnant women is an uncommon but complex urological and obstetric emergency with potentially catastrophic consequences. A multidisciplinary approach is key to timely diagnosis and appropriate management considering the well-being both of mother and foetus. Pre-emptive diagnosis and intervention may reduce complications. Level of evidence: 4