The legacy of terrestrial plant evolution on cell wall fine structure.

The evolution of land flora was an epochal event in the history of planet Earth. The success of plants, and especially flowering plants, in colonizing all but the most hostile environments required multiple mechanisms of adaptation. The mainly polysaccharide-based cell walls of flowering plants, which are indispensable for water transport and structural support, are one of the most important adaptations to life on land. Thus, development of vasculature is regarded as a seminal event in cell wall evolution, but the impact of further refinements and diversification of cell wall compositions and architectures on radiation of flowering plant families is less well understood. We approached this from a glyco-profiling perspective and, using carbohydrate microarrays and monoclonal antibodies, studied the cell walls of 287 plant species selected to represent important evolutionary dichotomies and adaptation to a variety of habitats. The results support the conclusion that radiation of flowering plant families was indeed accompanied by changes in cell wall fine structure and that these changes can obscure earlier evolutionary events. Convergent cell wall adaptations identified by our analyses do not appear to be associated with plants with similar lifestyles but that are taxonomically distantly related. We conclude that cell wall structure is linked to phylogeny more strongly than to habitat or lifestyle and propose that there are many approaches of adaptation to any given ecological niche.

The effects of empagliflozin on measured glomerular filtration rate and estimated extracellular and plasma volumes in patients with type 2 diabetes.

AIMS: To investigate the effects of empagliflozin on measured glomerular filtration rate (mGFR), estimated plasma volume (PV) and estimated extracellular volume (ECV) in a cohort of patients with type 2 diabetes (T2D) and high risk of cardiovascular events. MATERIALS AND METHODS: In this prespecified substudy of the randomized, placebo-controlled SIMPLE trial, patients with T2D at high risk of cardiovascular events were allocated to either empagliflozin 25 mg or placebo once daily for 13 weeks. The prespecified outcome was between-group change in mGFR, measured by the 51 Cr-EDTA method after 13 weeks; changes in estimated PV and estimated ECV were included. RESULTS: From April 4, 2017 to May 11, 2020, 91 participants were randomized. Of these, 45 patients from the empagliflozin group and 45 patients from the placebo group were included in the intention-to-treat analysis. Treatment with empagliflozin reduced mGFR by -7.9 mL/min (95% confidence interval [CI] -11.1 to -4.7; P < 0.001), estimated ECV by -192.5 mL (95% CI -318.0 to -66.9; P = 0.003) and estimated PV by -128.9 mL (95% CI -218.0 to 39.8; P = 0.005) at Week 13. CONCLUSIONS: Treatment with empagliflozin for 13 weeks reduced mGFR, estimated ECV and estimated PV in patients with T2D and high risk of cardiovascular events.

Reduction of cardiac adipose tissue volume with short-term empagliflozin treatment in patients with type 2 diabetes: A substudy from the SIMPLE randomized clinical trial.

OBJECTIVE: Ectopic accumulation of cardiac adipose tissue volume (CAT) has been associated with cardiac remodelling and cardiac dysfunction in type 2 diabetes and may be a future therapeutic target. In this substudy from the SIMPLE-trial, we investigated short-term empagliflozin therapy's effects on CAT in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Between 4 April 2017 and 11 May 2020, we randomized 90 patients with type 2 diabetes and established or high risk of cardiovascular disease to 25 mg empagliflozin or placebo for 13 weeks. The substudy focused on change in CAT evaluated by images acquired during 82 Rubidium-positron emissions tomography/computed tomography. The analysis included 78 patients who had at least one scan. Furthermore, we report on the relation to the concurrent effects on left ventricular mass, end-diastolic volume and end-systolic volume, body composition and glucometabolic status. RESULTS: Mean ± SD baseline CAT was 258.5 ± 117.9 ml. Empagliflozin reduced CAT after 13 weeks by 12.41 ml [95% CI (-23.83 to -0.99), p = .034] as compared with placebo. Similarly, left ventricular mass [-5.16 g, 95% CI (-8.80 to -1.52), p = .006], end-diastolic volume and end-systolic volume decreased with empagliflozin. In addition, significant improvements were observed in body composition, with reduced total fat mass, and in measures of glucose and lipid metabolism. However, no correlation was observed between changes in CAT and changes in cardiac parameters and change in CAT appeared mediated primarily by concurrent change in weight. CONCLUSIONS: Empagliflozin provides an early reduction of CAT; however, no association was observed with concurrent changes in cardiac volumetrics.

Effect on cardiac function among patients with type 2 diabetes following high-dose mineralocorticoid receptor antagonist using echocardiography; data from the MIRAD randomized clinical trial.

BACKGROUND: Early heart failure prevention is central in patients with type 2 diabetes, and mineralocorticoid receptor antagonists (MRAs) have shown to improve prognosis. We investigated the effect of high-dose MRA, eplerenone, on cardiac function and structure in patients with type 2 diabetes and established or increased risk of cardiovascular disease but without heart failure. METHODS: In the current randomized, placebo-controlled clinical trial, 140 patients with high-risk type 2 diabetes were randomized to high-dose eplerenone (100-200 mg daily) or placebo as add-on to standard care for 26 weeks. Left ventricular systolic and diastolic function, indexed left ventricular mass (LVMi), and global longitudinal strain (GLS) were assessed using echocardiography at baseline and after 26 weeks of treatment. RESULTS: Of the included patients, 138 (99%) had an echocardiography performed at least once. Baseline early diastolic in-flow velocity (E-wave) indexed by mitral annulus velocity (e') was mean (SD) 11.1 (0.5), with 31% of patients reaching above 12. No effect of treatment on diastolic function was observed measured by E/e' (0.0, 95%CI [-1.2 to 1.2], P = 0.992) or E/A (-0.1, 95%CI [-0.2 to 0.0], P = 0.191). Mean left ventricular ejection fraction (LVEF) at baseline was 59.0% (8.0). No improvement in systolic function was observed when comparing groups after 26 weeks (LVEF: 0.9, 95%CI [-1.1 to 2.8], P = 0.382; GLS: -0.4%, 95%CI [-1.5 to 0.6], P = 0.422), nor in LVMi (-3.8 g/m2 95%CI [-10.2 to 2.7], P = 0.246). CONCLUSION: In the present echo sub-study, no change in left ventricular function was observed following high-dose MRA therapy in patients with type 2 diabetes when evaluated by conventional echocardiography. TRIAL REGISTRATION: Date of registration 25/08/2015 (EudraCT number: 2015-002,519-14).

Diagnostic accuracy of focused deep venous, lung, cardiac and multiorgan ultrasound in suspected pulmonary embolism: a systematic review and meta-analysis.

OBJECTIVE: To determine the diagnostic accuracy of point-of-care ultrasound in suspected pulmonary embolism. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE, Embase, CINAHL and Cochrane library were searched on 2 July 2020 with no restrictions on the date of publication. Subject headings or subheadings combined with text words for the concepts of pulmonary embolism, ultrasound and diagnosis were used. ELIGIBILITY CRITERIA AND DATA ANALYSIS: Eligible studies reported sensitivity and specificity of deep venous, lung, cardiac or multiorgan ultrasound in patients with suspected pulmonary embolism, using an adequate reference-test. Prospective, cross-sectional and retrospective studies were considered for eligibility. No restrictions were made on language. Studies were excluded if a control group consisted of healthy volunteers or if transesophageal or endobronchial ultrasound was used. Risk of bias was assessed using quality assessment of diagnostic accuracy studies-2. Meta-analysis of sensitivity and specificity was performed by construction of hierarchical summary receiver operator curves. I2 was used to assess the study heterogeneity. MAIN OUTCOME MEASURES: The primary outcome was overall sensitivity and specificity of reported ultrasound signs, stratified by organ approach (deep venous, lung, cardiac and multiorgan). Secondary outcomes were stratum-specific sensitivity and specificity within subgroups defined by pretest probability of pulmonary embolism. RESULTS: 6378 references were identified, and 70 studies included. The study population comprised 9664 patients with a prevalence of pulmonary embolism of 39.9% (3852/9664). Risk of bias in at least one domain was found in 98.6% (69/70) of included studies. Most frequently, 72.8% (51/70) of studies reported >24 hours between ultrasound examination and reference test or did not disclose time interval at all. Level of heterogeneity ranged from 0% to 100%. Most notable ultrasound signs were bilateral compression of femoral and popliteal veins (22 studies; 4708 patients; sensitivity 43.7% (36.3% to 51.4%); specificity 96.7% (95.4% to 97.6%)), presence of at least one hypoechoic pleural-based lesion (19 studies; 2134 patients; sensitivity 81.4% (73.2% to 87.5%); specificity 87.4% (80.9% to 91.9%)), D-sign (13 studies; 1579 patients; sensitivity 29.7% (24.6% to 35.4%); specificity 96.2% (93.1% to 98.0%)), visible right ventricular thrombus (5 studies; 995 patients; sensitivity 4.7% (2.7% to 8.1%); specificity 100% (99.0% to 100%)) and McConnell's sign (11 studies; 1480 patients; sensitivity 29.1% (20.0% to 40.1%); specificity 98.6% (96.7% to 99.4%)). CONCLUSION: Several ultrasound signs exhibit a high specificity for pulmonary embolism, suggesting that implementation of ultrasound in the initial assessment of patients with suspected pulmonary embolism may improve the selection of patients for radiation imaging. PROSPERO REGISTRATION NUMBER: CRD42020184313.

Does the Addition of Radial Endobronchial Ultrasound Improve the Diagnostic Yield of Electromagnetic Navigation Bronchoscopy? A Systematic Review.

BACKGROUND: Lung cancer is the leading cause of cancer-related death worldwide. Early diagnosis is crucial to increased survival rates. Radial endobronchial ultrasound (rEBUS) and electromagnetic navigation bronchoscopy (ENB) have been developed for the diagnosis of small lung lesions. The aim of this systematic review was to evaluate whether the combination of rEBUS and ENB is superior to ENB alone. METHOD: A systematic search was performed using MEDLINE, Embase, and Cochrane Library databases on "ENB," and conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The project was registered with PROSPERO, number CRD42020214682. RESULTS: In total, 2,092 studies were identified through a literature search. Five studies were included in the final review. One study found that the addition of rEBUS increased diagnostic yield, while another concluded the converse. Three studies did not have significant results. Meta-analysis was not feasible due to heterogeneity and the small number of studies. CONCLUSION: As the current evidence on the topic is sparse and heterogeneous, it is not possible to conclude whether the addition of rEBUS to ENB has a significant impact on diagnostic yield. Further studies are needed to illuminate this question in order to ensure optimal choice of endoscopic technique as well as used time and resources. The project received funding from the Region of Southern Denmark's PhD fund.

Clinical Applications of Contrast-Enhanced Thoracic Ultrasound (CETUS) Compared to Standard Reference Tests: A Systematic Review.

INTRODUCTION: Contrast-enhanced ultrasound is utilized in an increasing array of medical fields, including thoracic medicine. However, the technique is still relatively new and only sporadically mentioned in current guidelines and recommendations. The aim of this systematic review is to provide a literature overview and to critically appraise the current clinical applications of contrast-enhanced thoracic ultrasound (CETUS). MATERIALS AND METHODS: A systematic literature search using major electronic databases and in accordance with PRISMA guidelines was performed. Studies with a primary focus on CETUS of thoracic disorders compared to a standard reference test were included. The QUADAS-2 tool was used for quality assessment of the studies. RESULTS: The search identified 43 articles: 1 randomized controlled study, 6 non-randomized controlled studies, 16 non-randomized non-controlled studies, 5 case series, 10 single case reports, and 5 animal studies. The overall risk of bias was judged to be high. Diagnostic accuracy measurements of noninvasive applications of CETUS were only reported in a few studies and they were too dissimilar for meta-analysis. Six studies compared CETUS-guided versus ultrasound-guided transthoracic needle biopsy of thoracic masses. They individually reported a significant increase in diagnostic accuracy in favor of CETUS guidance but were too heterogeneous for meta-analysis. CONCLUSION: The current literature on CETUS is overall heterogeneous with a few high evidence level studies, small study populations and a high risk of bias. CETUS-guided biopsy is the most frequent clinical application and increases diagnostic accuracy compared to ultrasound guidance by an average of 14.6 percentage points.

European Respiratory Society statement on thoracic ultrasound.

Thoracic ultrasound is increasingly considered to be an essential tool for the pulmonologist. It is used in diverse clinical scenarios, including as an adjunct to clinical decision making for diagnosis, a real-time guide to procedures and a predictor or measurement of treatment response. The aim of this European Respiratory Society task force was to produce a statement on thoracic ultrasound for pulmonologists using thoracic ultrasound within the field of respiratory medicine. The multidisciplinary panel performed a review of the literature, addressing major areas of thoracic ultrasound practice and application. The selected major areas include equipment and technique, assessment of the chest wall, parietal pleura, pleural effusion, pneumothorax, interstitial syndrome, lung consolidation, diaphragm assessment, intervention guidance, training and the patient perspective. Despite the growing evidence supporting the use of thoracic ultrasound, the published literature still contains a paucity of data in some important fields. Key research questions for each of the major areas were identified, which serve to facilitate future multicentre collaborations and research to further consolidate an evidence-based use of thoracic ultrasound, for the benefit of the many patients being exposed to clinicians using thoracic ultrasound.

Association of age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer.

PURPOSE: To assess the association of patient age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: We analyzed data from 1105 patients with MIBC. Patients age was evaluated as continuous variable and stratified in quartiles. Pathologic objective response (pOR; ypT0-Ta-Tis-T1N0) and pathologic complete response (pCR; ypT0N0), as well survival outcomes were assessed. We used data of 395 patients from The Cancer Genome Atlas (TCGA) to investigate the prevalence of TCGA molecular subtypes and DNA damage repair (DDR) gene alterations according to patient age. RESULTS: pOR was achieved in 40% of patients. There was no difference in distribution of pOR or pCR between age quartiles. On univariable logistic regression analysis, patient age was not associated with pOR or pCR when evaluated as continuous variables or stratified in quartiles (all p > 0.3). Median follow-up was 18 months (IQR 6-37). On Cox regression and competing risk regression analyses, age was not associated with survival outcomes (all p > 0.05). In the TCGA cohort, patient with age ≤ 60 years has 7% less DDR gene mutations (p = 0.59). We found higher age distribution in patients with luminal (p < 0.001) and luminal infiltrated (p = 0.002) compared to those with luminal papillary subtype. CONCLUSIONS: While younger patients may have less mutational tumor burden, our analysis failed to show an association of age with response to preoperative chemotherapy or survival outcomes. Therefore, the use of preoperative chemotherapy should be considered regardless of patient age.

High preharvest donor Foxp3 mRNA level predicts late relapse of acute lymphoblastic leukaemia after haematopoietic stem cell transplantation.

OBJECTIVES: The curative effect of allogeneic haematopoietic stem cell transplantation (HSCT) for acute leukaemia is due in part to the donor T cell-mediated graft-versus-leukaemia immune reaction (GvL). Several studies have suggested that donor CD25+CD4+Foxp3+regulator T cells (Tregs) may decrease graft-versus-host disease (GvHD) without abrogating GVL. This notion may need modification in acute lymphoblastic leukaemia (ALL). METHODS: Foxp3 mRNA level was measured by qPCR in preharvest donor blood CD4+ T cells. The study comprised 45 patients with ALL in 1st or 2nd CR who received myeloablative HSCT using T-replete bone marrow grafts. RESULTS: Relapse occurred in 17 patients median 363 days after HSCT. The relapse risk was estimated by Cox univariate and multivariate proportional hazard regression. The proportionality assumption was met by analysing the preharvest donor Foxp3 mRNA level as a time-dependent covariate. Early relapse was not modified by the Foxp3 mRNA level. However, a higher Foxp3 mRNA level was associated with a significantly increased relapse risk after day 363 after transplantation, compatible with inhibition of GvL. In contrast, a higher preharvest donor CD4+ T-cell concentration was associated with reduced relapse risk. CONCLUSION: A higher preharvest donor Foxp3 mRNA level may be predictive of late ALL relapse after HSCT.

How I Do It: Technical report on surgically-initiated rectus sheath catheter using catheter-over-needle assembly.

Development of chronic postsurgical pain following major abdominal or pelvic surgeries is increasingly recognized. Multimodal analgesia including regional anesthesia such as rectus sheath block is growing in popularity. While the literature mainly describes ultrasound-guided rectus sheath blocks, there are many advantages to surgically-initiated rectus sheath catheter performed at the end of surgery. In this technical description, we describe the rationale and technique of surgical insertion of rectus sheath catheters following major urologic surgery with midline incision which is routinely performed by urologists at our institution. Furthermore, we would like to highlight the type of catheter used during rectus sheath catheter insertion, namely the catheter-over-needle assembly. It is simple to insert while minimizes complications such as local anesthetic leakage at the insertion site causing dressing disruption and premature catheter dislodgement, as the catheter-over-needle assembly fits snugly with the skin after insertion.

Allograft and patient survival after sequential HSCT and kidney transplantation from the same donor-A multicenter analysis.

Tolerance induction through simultaneous hematopoietic stem cell and renal transplantation has shown promising results, but it is hampered by the toxicity of preconditioning therapies and graft-versus-host disease (GVHD). Moreover, renal function has never been compared to conventionally transplanted patients, thus, whether donor-specific tolerance results in improved outcomes remains unanswered. We collected follow-up data of published cases of renal transplantations after hematopoietic stem cell transplantation from the same donor and compared patient and transplant kidney survival as well as function with caliper-matched living-donor renal transplantations from the Austrian dialysis and transplant registry. Overall, 22 tolerant and 20 control patients were included (median observation period 10 years [range 11 months to 26 years]). In the tolerant group, no renal allograft loss was reported, whereas 3 were lost in the control group. Median creatinine levels were 85 µmol/l (interquartile range [IQR] 72-99) in the tolerant cohort and 118 µmol/l (IQR 99-143) in the control group. Mixed linear-model showed around 29% lower average creatinine levels throughout follow-up in the tolerant group (P < .01). Our data clearly show stable renal graft function without long-term immunosuppression for many years, suggesting permanent donor-specific tolerance. Thus sequential transplantation might be an alternative approach for future studies targeting tolerance induction in renal allograft recipients.

CD25 Blockade Delays Regulatory T Cell Reconstitution and Does Not Prevent Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation.

Daclizumab, a humanized monoclonal antibody, binds CD25 and blocks formation of the IL-2 receptor on T cells. A study of daclizumab as acute graft-versus-host disease (GVHD) prophylaxis after unrelated bone marrow transplantation was conducted before the importance of CD25+FOXP3+ regulatory T cells (Tregs) was recognized. Tregs can abrogate the onset of GVHD. The relation between Tregs and a graft-versus-malignancy effect is not fully understood. An international, multicenter, double-blind clinical trial randomized 210 adult or pediatric patients to receive 5 weekly doses of daclizumab at 0.3 mg/kg (n = 69) or 1.2 mg/kg (n = 76) or placebo (n = 65) after unrelated marrow transplantation for treatment of hematologic malignancies or severe aplastic anemia. The risk of acute GVHD did not differ among the groups (P = .68). Long-term follow-up of clinical outcomes and correlative analysis of peripheral blood T cell phenotype suggested that the patients treated with daclizumab had an increased risk of chronic GVHD (hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.0 to 2.3; P = .08) and a decreased risk of relapse (HR, 0.57; 95% CI, 0.3 to 1.0; P = .05), but similar survival (HR, 0.89; 95% CI, 0.6 to 1.3; P = .53). T cells from a subset of patients (n = 107) were analyzed by flow cytometry. Compared with placebo, treatment with daclizumab decreased the proportion of Tregs among CD4 T cells at days 11-35 and increased the proportion of central memory cells among CD4 T cells at 1 year. Prophylactic administration of daclizumab does not prevent acute GVHD, but may increase the risk of chronic GVHD and decrease the risk of relapse. By delaying Treg reconstitution and promoting immunologic memory, anti-CD25 therapy may augment alloreactivity and antitumor immunity.

Assessment of Basic Thoracic Ultrasound Skills in Immersive Virtual Reality: Gathering Validity Evidence.

OBJECTIVE: Operator skills are essential for thoracic ultrasound (TUS) to ensure diagnostic accuracy. Immersive virtual reality (IVR) has shown potential within medical education but never for assessment of TUS skills. This study was aimed at developing an IVR test for assessing TUS skills, gathering validity evidence and establishing a pass/fail score. METHODS: An expert panel developed a test based on the TUS protocol by the European Respiratory Society (ERS), including a tutorial and two clinical cases (pleural effusion and interstitial syndrome), using an IVR platform (VitaSim, Odense, Denmark). Four anterior, four lateral and six posterior zones were available for examination and decision of diagnosis. Each correct examination equaled one point. The contrasting groups' method was used to set a pass/fail score. RESULTS: Data were collected during the 2022 ERS Congress. We included 13 novices (N, experience: 0 TUS), 22 intermediates (I, 1-50 TUS) and 11 experienced clinicians (E, >50 TUS). Cronbach's α was 0.86. The total mean point scores in case 1 (C1) were (N) 5.0 ± 2.7, (I) 7.3 ± 2.4 and (E) 8.7 ± 1.3, and the scores in case 2 (C2) were (N) 4.5 ± 1.8, (I) 6.7 ± 2.3 and (E) 8.5 ± 2.1. Significant differences were found between N and I for C1 (p = 0.007) and C2 (p = 0.02), I and E for C1 (p = 0.04) and C2 (p = 0.019) and N and E for C1 (p < 0.001) and C2 (p < 0.001). The pass/fail score was 7 points in each case. CONCLUSION: We established an IVR test that can distinguish between operators with different TUS skills. This enables a standardized, objective and evidence-based approach to assessment of TUS skills.

Persistently Decreased Quality of Life and its Determinants in Previous Illicit Androgen Users.

BACKGROUND AND OBJECTIVES: Quality of life (QoL) has never been assessed in previous illicit users of androgens years following androgen cessation. Therefore, the objective of this study was to assess QoL in previous illicit androgen users compared with current illicit androgen users and controls who had never used androgens. METHODS: Cross-sectional study including men involved in recreational strength training grouped according to their history of androgen use. We used the RAND Short-Form-36 questionnaire to assess physical and mental health-related QoL. RESULTS: We included 77 previous and 118 current androgen users and 39 healthy nonusers. The mean (SD) age of all participants was 33 (8) years. The elapsed duration since androgen cessation, geometric mean (95% CI), was 2.0 (1.5-2.6) years in former users. Median (25th-75th percentiles) serum total testosterone was lower in former users than controls, 14 (11-17) vs 19 (16-21) nmol/L, P < .001. Previous users displayed lower mean (SD) across both mental and physical (PCS) component summary scores, 48 (10) vs 54 (4) (P = .004) and 48 (9) vs 53 (3) (P = .002) compared with controls.Using multivariate linear regressions, evaluating physical and mental component scores as dependent variables, lower serum total testosterone, longer duration since androgen cessation, study recruitment from an endocrine outpatient clinic, and established chronic diseases were all independently associated with reduced QoL in previous users, P < .05. CONCLUSIONS: Previous illicit androgen users exhibited reduced QoL 2 years after androgen discontinuation, which may be a persistent condition.

Fluorine-18 Prostate-Specific Membrane Antigen-1007 PET/CT vs Multiparametric MRI for Locoregional Staging of Prostate Cancer.

Importance: Prostate-specific membrane antigen (PSMA) demonstrates overexpression in prostate cancer and correlates with tumor aggressiveness. PSMA positron emission tomography (PET) is superior to conventional imaging for the metastatic staging of prostate cancer per current research but studies of second-generation PSMA PET radioligands for locoregional staging are limited. Objective: To determine the accuracy of fluorine-18 PSMA-1007 PET/computed tomography (18F-PSMA-1007 PET/CT) compared to multiparametric magnetic resonance imaging (MRI) in the primary locoregional staging of intermediate-risk and high-risk prostate cancers. Design, Setting, and Participants: The Next Generation Trial was a phase 2 prospective validating paired cohort study assessing the accuracy of 18F-PSMA-1007 PET/CT and MRI for locoregional staging of prostate cancer, with results of histopathologic examination as the reference standard comparator. Radiologists, nuclear medicine physicians, and pathologists were blinded to preoperative clinical, pathology, and imaging data. Patients underwent all imaging studies and radical prostatectomies at 2 tertiary care hospitals in Alberta, Canada. Eligible participants included men with intermediate-risk or high-risk prostate cancer who consented to radical prostatectomy. Participants who underwent radical prostatectomy were included in the final analysis. Patients were recruited between March 2022 and June 2023, and data analysis occurred between July 2023 and December 2023. Exposures: All participants underwent both 18F-PSMA-1007 PET/CT and MRI within 2 weeks of one another and before radical prostatectomy. Main Outcomes and Measures: The primary outcome was the correct identification of the prostate cancer tumor stage by each imaging test. The secondary outcomes were correct identification of the dominant nodule, laterality, extracapsular extension, and seminal vesical invasion. Results: Of 150 eligible men with prostate cancer, 134 patients ultimately underwent radical prostatectomy (mean [SD] age at prostatectomy, 62.0 [5.7] years). PSMA PET was superior to MRI for the accurate identification of the final pathological tumor stage (61 [45%] vs 38 [28%]; P = .003). PSMA PET was also superior to MRI for the correct identification of the dominant nodule (126 [94%] vs 112 [83%]; P = .01), laterality (86 [64%] vs 60 [44%]; P = .001), and extracapsular extension (100 [75%] vs 84 [63%]; P = .01), but not for seminal vesicle invasion (122 [91%] vs 115 [85%]; P = .07). Conclusions and Relevance: In this phase 2 prospective validating paired cohort study, 18F-PSMA-1007 PET/CT was superior to MRI for the locoregional staging of prostate cancer. These findings support PSMA PET in the preoperative workflow of intermediate-risk and high-risk tumors.

Comparison of oncological outcomes for open and laparoscopic radical nephroureterectomy: results from the Canadian Upper Tract Collaboration.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?Open radical nephroureterectomy (ORNU) with excision of the ipsilateral bladder cuff is a standard treatment for upper tract urothelial carcinoma (UTUC). However, over the past decade laparoscopic RNU (LRNU) has emerged as a minimally invasive surgical alternative. Data comparing the oncological efficacy of ORNU and LRNU have reported mixed results and the equivalence of these surgical techniques have not yet been established. We found that surgical approach was not independently associated with overall or disease-specific survival; however, there was a trend toward an independent association between LRNU and poorer recurrence-free survival (RFS). To our knowledge, this is the first large, multi-institutional analysis to show a trend toward inferior RFS in patients with UTUC treated with LRNU. OBJECTIVE: To examine the association between surgical approach for radical nephroureterectomy (RNU) and clinical outcomes in a large, multi-institutional cohort, as there are limited data comparing the oncological efficacy of open RNU (ORNU) and laparoscopic RNU (LRNU) for upper urinary tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: Institutional RNU databases containing detailed information on patients with UTUC treated between 1994 and 2009 were obtained from 10 academic centres in Canada. Data were collected on 1029 patients and combined into a relational database formatted with patient characteristics, pathological characteristics, and survival status. Surgical approach was classified as ORNU (n = 403) or LRNU (n = 446). The clinical outcomes were overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS). The Kaplan-Meier method and Cox proportional regression analysis were used to analyse survival data. RESULTS: Data were evaluable for 849 of 1029 (82.5%) patients. The median (interquartile range) follow-up duration was 2.2 (0.6-5.0) years. The predicted 5-year OS (67% vs 68%, log-rank P = 0.19) and DSS (73% vs 76%, log-rank P = 0.32) rates did not differ between the ORNU and LRNU groups; however, there was a trend toward an improved predicted 5-year RFS rate in the ORNU group (43% vs 33%, log-rank P = 0.06). Multivariable Cox proportional regression analysis showed that surgical approach was not significantly associated with OS (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.63-1.27, P = 0.52) or DSS (HR 0.90, 95% CI 0.60-1.37, P = 0.64); however, there was a trend toward an independent association between surgical approach and RFS (HR 1.24, 95% CI 0.98-1.57, P = 0.08). CONCLUSION: Surgical approach was not independently associated with OS or DSS but there was a trend toward an independent association between LRNU and poorer RFS. Further prospective evaluation is needed.

Association between urinary diversion and quality of life after radical cystectomy.

INTRODUCTION: We examined the association between type of urinary diversion and quality of life (QoL) in patients who underwent radical cystectomy for primary bladder cancer using a validated, disease-specific instrument. MATERIALS AND METHODS: A cohort of 314 consecutive patients treated with radical cystectomy and urinary diversion for primary bladder cancer between January 2000 and December 2006 was analyzed. Participants were mailed the validated Functional Assessment of Cancer Therapy-Vanderbilt Cystectomy Index (FACT-VCI) questionnaire. Univariable and multivariable linear regression analyses were used to examine the association between type of urinary diversion (ileal conduit versus orthotopic neobladder) and QoL. RESULTS: Eighty-four out of 168 (50% response rate) evaluable patients completed the FACT-VCI questionnaire. The median follow up duration was 5.6 years (range, 2.1 to 9.3 years). ANOVA showed statistically significant differences favoring orthotopic neobladder urinary diversion with more favorable QoL scores on the FACT-VCI (mean difference 5.6 points, p = .03) and radical cystectomy-specific domain (mean difference 2.9 points, p = .05). However, multivariable linear regression analyses showed no statistically significant association between the type of urinary diversion and QoL (FACT-VCI: ß = 4.1 points, p = .177; radical cystectomy-specific: ß = 1.5 points, p = .390). CONCLUSIONS: Type of urinary diversion was not associated with QoL after radical cystectomy. Randomized controlled trials comparing types of urinary diversion using validated, disease-specific QoL instruments are needed.