A phase I clinical trial of oncolytic adenovirus mediated suicide and interleukin-12 gene therapy in patients with recurrent localized prostate adenocarcinoma.

In a phase I dose escalation and safety study (NCT02555397), a replication-competent oncolytic adenovirus expressing yCD, TK and hIL-12 (Ad5-yCD/mutTKSR39rep-hIL-12) was administered in 15 subjects with localized recurrent prostate cancer (T1c-T2) at increasing doses (1 × 1010, to 1 × 1012 viral particles) followed by 7-day treatment of 5-fluorocytosine (5-FC) and valganciclovir (vGCV). The primary endpoint was toxicity through day 30 while the secondary and exploratory endpoints were quantitation of IL-12, IFNγ, CXCL10 and peripheral blood mononuclear cells (PBMC). The study maximum tolerated dose (MTD) was not reached indicating 1012 viral particles was safe. Total 115 adverse events were observed, most of which (92%) were grade 1/2 that did not require any treatment. Adenoviral DNA was detected only in two patients. Increase in IL-12, IFNγ, and CXCL10 was observed in 57%, 93%, and 79% patients, respectively. Serum cytokines demonstrated viral dose dependency, especially apparent in the highest-dose cohorts. PBMC analysis revealed immune system activation after gene therapy in cohort 5. The PSA doubling time (PSADT) pre and post treatment has a median of 1.55 years vs 1.18 years. This trial confirmed that replication-competent Ad5-IL-12 adenovirus (Ad5-yCD/mutTKSR39rep-hIL-12) was well tolerated when administered locally to prostate tumors.

Long-term outcome of patients with combined post- and pre-capillary pulmonary hypertension.

Aims: Pulmonary hypertension (PH) is a complex clinical condition, and left heart disease is the leading cause. Little is known about the epidemiology and prognosis of combined post- and pre-capillary PH (CpcPH). Methods and results: This retrospective analysis of the Swiss PH Registry included incident patients with CpcPH registered from January 2001 to June 2019 at 13 Swiss hospitals. Patient baseline characteristics [age, sex, mean pulmonary artery pressure (mPAP), pulmonary artery wedge pressure (PAWP), pulmonary vascular resistance (PVR), and risk factors, including World Health Organization (WHO)-functional class (FC), 6 min walk distance (6MWD), and N-terminal pro-brain natriuretic peptide (NT-proBNP), treatment, days of follow-up, and events (death or loss to follow-up) at last visit] were analysed by Kaplan-Meier and Cox regression analyses. Two hundred and thirty-one patients (59.3% women, age 65 ± 12 years, mPAP 48 ± 11 mmHg, PAWP 21 ± 5 mmHg, PVR 7.2 ± 4.8 WU) were included. Survival analyses showed a significantly longer survival for women [hazard ratio (HR) 0.58 (0.38-0.89); P = 0.01] and a higher mortality risk for mPAP > 46 mmHg [HR 1.58 (1.03-2.43); P = 0.04] but no association with age or PVR. Patients stratified to high risk according to four-strata risk assessment had an increased mortality risk compared with patients stratified to low-intermediate risk [HR 2.44 (1.23-4.84); P = 0.01]. A total of 46.8% of CpcPH patients received PH-targeted pharmacotherapy; however, PH-targeted medication was not associated with longer survival. Conclusion: Among patients with CpcPH, women and patients with an mPAP ≤46 mmHg survived longer. Furthermore, risk stratification by using non-invasively assessed risk factors, such as WHO-FC, 6MWD, and NT-proBNP, as proposed for pulmonary arterial hypertension, stratified survival in CpcPH, and might be helpful in the management of these patients.

Impact of public health interventions to curb SARS-CoV-2 spread assessed by an evidence-educated Delphi panel and tailored SEIR model.

Aim: To use a Delphi-panel-based assessment of the effectiveness of different non-pharmaceutical interventions (NPI) in order to retrospectively approximate and to prospectively predict the SARS-CoV-2 pandemic progression via a SEIR model (susceptible, exposed, infectious, removed). Methods: We applied an evidence-educated Delphi-panel approach to elicit the impact of NPIs on the SARS-CoV-2 transmission rate R0 in Germany. Effectiveness was defined as the product of efficacy and compliance. A discrete, deterministic SEIR model with time step of 1 day, a latency period of 1.8 days, duration of infectiousness of 5 days, and a share of the total population of 15% assumed to be protected by immunity was developed in order to estimate the impact of selected NPI measures on the course of the pandemic. The model was populated with the Delphi-panel results and varied in sensitivity analyses. Results: Efficacy and compliance estimates for the three most effective NPIs were as follows: test and isolate 49% (efficacy)/78% (compliance), keeping distance 42%/74%, personal protection masks (cloth masks or other face masks) 33%/79%. Applying all NPI effectiveness estimates to the SEIR model resulted in a valid replication of reported occurrence of the German SARS-CoV-2 pandemic. A combination of four NPIs at consented compliance rates might curb the CoViD-19 pandemic. Conclusion: Employing an evidence-educated Delphi-panel approach can support SARS-CoV-2 modelling. Future curbing scenarios require a combination of NPIs. A Delphi-panel-based NPI assessment and modelling might support public health policy decision making by informing sequence and number of needed public health measures. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-021-01566-2.

Therapeutic anticoagulation to prevent thrombosis, coagulopathy, and mortality in severe COVID-19: The Swiss COVID-HEP randomized clinical trial.

Background: Hospitalized patients with COVID-19 suffered initially from high rates of venous thromboembolism (VTE), with possible associations between therapeutic anticoagulation and better clinical outcomes in observational studies. Objective: To test whether therapeutic anticoagulation improves clinical outcomes in severe COVID-19. Patients/Methods: In this multicenter, open-label, randomized controlled trial, we recruited acutely ill medical COVID-19 patients with D-dimer >1000 ng/ml or critically ill COVID-19 patients in four Swiss hospitals, from April 2020 until June 2021, with a 30-day follow-up. Participants were randomized to in-hospital therapeutic anticoagulation versus low-dose anticoagulation in acutely ill participants/intermediate-dose anticoagulation in critically ill participants, with enoxaparin or unfractionated heparins. The primary outcome was a centrally adjudicated composite of 30-day all-cause mortality, VTE, arterial thrombosis, and disseminated intravascular coagulopathy (DIC), with screening for proximal deep vein thrombosis. Results: Among 159 participants, 55.3% were critically ill and 94.3% received corticosteroids. Before study inclusion, pulmonary embolism had been excluded in 71.7%. The primary outcome occurred in 4/79 participants randomized to therapeutic anticoagulation and 4/80 to low/intermediate anticoagulation (5.4% vs. 5.0%; risk difference +0.4%; adjusted hazard ratio 0.76, 95% confidence interval 0.18-3.21), including three deaths in each group. All primary outcomes and major bleeding (n = 3) occurred in critically ill participants. There was no asymptomatic proximal deep vein thrombosis and no difference in major bleeding. Conclusions: Among patients with severe COVID-19 treated with corticosteroids and with exclusion of pulmonary embolism at hospital admission for most, risks of mortality, thrombotic outcomes, and DIC were low at 30 days. The lack of benefit of therapeutic anticoagulation was too imprecise for definite conclusions.

Disease characteristics and clinical outcome over two decades from the Swiss pulmonary hypertension registry.

Pulmonary hypertension (PH), especially pulmonary arterial and chronic thromboembolic pulmonary hypertension (PAH/CTEPH), are rare and progressive conditions. Despite recent advances in treatment and prognosis, PH is still associated with impaired quality of life and survival. Long-term PH-registry data provide information on the changing PH-epidemiology and may help to direct resources to patient's needs. This retrospective analysis of the Swiss Pulmonary Hypertension Registry includes patients newly diagnosed with PH (mainly PAH/CTEPH) registered from January 2001 to June 2019 at 13 Swiss hospitals. Patient characteristics (age, body mass index, gender, diagnosis), hemodynamics at baseline, treatment, days of follow-up, and events (death, transplantation, pulmonary endarterectomy, or loss to follow-up) at last visit were analyzed. Patients were stratified into four time periods according to their date of diagnosis. Survival was analyzed overall and separately for PAH/CTEPH and time periods. 1427 PH patients were included (thereof 560 PAH, 383 CTEPH). Over the years, age at baseline (mean ± SD) significantly increased from 59 ± 14 years in 2001-2005 to 66 ± 14 years in 2016-2019 (p < 0.001) while the gender distribution tended toward equality. Mean pulmonary artery pressure and pulmonary vascular resistance significantly decreased over time (from 46 ± 15 to 41 ± 11 mmHg, respectively, 9 ± 5 to 7 ± 4 WU, p < 0.001). Three-year survival substantially increased over consecutive periods from 69% to 91% (for PAH 63%-95%, for CTEPH 86%-93%) and was poorer in PAH than CTEPH independently of time period (p < 0.001). Most patients were treated with mono- or combination therapy and an increasing number of CTEPH underwent pulmonary endarterectomy (40% 2016-2019 vs. 15% 2001-2005). This long-term PH registry reveals that over two decades of observation, newly diagnosed patients are older, less predominantly female, have less impaired hemodynamics and a better survival.

Prevalence and risk factors for venous thromboembolic events in critically ill patients with SARS-CoV-2 infection: a prospective observational study.

BACKGROUND: The majority of prevalence studies on deep vein thrombosis (DVT) in severe COVID-19 patients are retrospective with DVT assessment based on clinical suspicion. Our aim was to prospectively and systematically estimate the occurrence of DVT in critically-ill mechanically-ventilated patients, and to identify potential risk factors for DVT occurrence and mortality. METHODS: All patients with COVID-19 admitted to our 45 beds in the Intensive Care Unit (ICU) between March 6, 2020, and April 18, 2020, requiring invasive ventilatory support were daily screened for DVT with lower extremities and jugular veins ultrasonography. Univariate and multivariable logistic regression models were performed in order to identify predictors of DVT and mortality. RESULTS: Seventy-six patients were included in the final analysis (56 men, mean age 67 years, median SOFA=7 points, median SAPS II=41 points, median PaO2/Fi02=10.8 kPa). The period prevalence of DVT was 40.8%. Thirty-one DVTs were diagnosed. Twenty-five DVTs (80.6% of total DVTs) were catheter-related, mainly in the jugular veins. Twenty-six DVTs (83.9%) occurred in patients receiving enhanced antithrombotic prophylaxis. No independent variable was predictive of DVT occurrence. Twenty-eight patients (36.8%) died during the ICU stay. Age and SOFA score were independently associated with mortality. CONCLUSIONS: A high number of critically-ill mechanically-ventilated COVID-19 patients developed a DVT. The majority of DVTs were catheter-related and occurred under intensive prophylactic anticoagulation. Routine ultrasound of the jugular veins should be suggested in this patient population, and in particular in presence of a central venous catheter.

Clonal evaluation of prostate cancer molecular heterogeneity in biopsy samples by dual immunohistochemistry and dual RNA in situ hybridization.

Prostate cancer is frequently multifocal. Although there may be morphological variation, the genetic underpinnings of each tumor are not clearly understood. To assess the inter and intra tumor molecular heterogeneity in prostate biopsy samples, we developed a combined immunohistochemistry and RNA in situ hybridization method for the simultaneous evaluation of ERG, SPINK1, ETV1, and ETV4. Screening of 601 biopsy cores from 120 consecutive patients revealed multiple alterations in a mutually exclusive manner in 37% of patients, suggesting multifocal tumors with considerable genetic differences. Furthermore, the incidence of molecular heterogeneity was higher in African Americans patients compared with Caucasian American patients. About 47% of the biopsy cores with discontinuous tumor foci showed clonal differences with distinct molecular aberrations. ERG positivity occurred in low-grade cancer, whereas ETV4 expression was observed mostly in high-grade cancer. Further studies revealed correlation between the incidence of molecular markers and clinical and pathologic findings, suggesting potential implications for diagnostic pathology practice, such as defining dominant tumor nodules and discriminating juxtaposed but molecularly different tumors of different grade patterns.

Feasibility and safety of flush endovenous laser ablation of the great saphenous vein up to the saphenofemoral junction.

OBJECTIVE: The optimal ablation distance from the catheter tip to the common femoral vein during endovenous laser ablation (EVLA) of the great saphenous vein (GSV) is a matter of debate. In this study, we evaluated the feasibility and safety of flush ablation (fEVLA) of the GSV. METHODS: This single-center, retrospective analysis of prospectively collected data included all consecutive fEVLA interventions of the GSV between September 2017 and October 2018. Interventions were performed with a 1470-nm radially emitting fiber. Primary end points were technical feasibility of fEVLA and endovenous heat-induced thrombosis (EHIT) class 2 to class 4. Secondary end points were procedure-related complications; anatomic success at week 6; and flush occlusion at day 1, day 10, and week 6. RESULTS: A total of 135 consecutive intended fEVLA procedures were performed in 113 patients (86 female, 27 male). The average body mass index was 24.9 ± 4.3 kg/m2. The Clinical, Etiology, Anatomy, and Pathophysiology (CEAP) clinical class for these patients was C2 in 78 (57.8%), C3 in 48 (35.6%), C4 in 8 (5.9%), and C5 in 1 (0.7%). The GSV diameter at the saphenofemoral junction was 9.4 ± 2.7 mm with a maximum of 16 mm. In 126 cases (93.3%), concomitant treatment of tributaries with phlebectomy or foam sclerotherapy was performed. In 127 cases (94.1%), fEVLA was technically feasible; in 8 cases (5.9%), appropriate catheter tip placement was not possible. In these cases, "standard" GSV ablation 10 to 20 mm distal to the saphenofemoral junction was performed. In the remaining 127 cases, one (0.8%) EHIT class 2 and one (0.8%) EHIT class 3 developed at day 10. After a 2- to 3-week course of anticoagulation with rivaroxaban, these EHIT cases resolved without sequelae. Furthermore, one (0.8%) superficial vein thrombosis and one (0.8%) calf vein thrombosis at the site of phlebectomy were observed. No local groin complication occurred. Flush occlusion was observed in 94.5%, 95.3%, and 88.2% of the cases at day 1, day 10, and week 6, respectively. Multivariate regression analysis revealed no significant association between flush ablation at day 1 and age, body mass index, CEAP class, fiber type, maximum vein diameter, or applied joules per centimeter. CONCLUSIONS: The results of this study suggest that fEVLA of the GSV using a radial emitting laser is feasible and seems to be safe.

Clonal evaluation of early onset prostate cancer by expression profiling of ERG, SPINK1, ETV1, and ETV4 on whole-mount radical prostatectomy tissue.

BACKGROUND: Expression profiles of erythroblast transformation-specific (ETS)-related gene fusions and serine protease inhibitor Kazal-type 1 (SPINK1) in early onset prostate cancer have not been thoroughly explored. METHODS: We retrieved 151 radical prostatectomy specimens from young men with prostate cancer (<55 years) and characterized the expression of ETS-related gene (ERG), SPINK1, ETS Variant 1 (ETV1), and ETV4 by dual immunohistochemistry and dual RNA in situ hybridization. Age, race, family history, preoperative prostate-specific antigen, biochemical recurrence, and pathological variables using whole-mount radical prostatectomy tissue were collected. RESULTS: A total of 313 tumor nodules from 151 men including 68 (45%) Caucasians and 61 (40%) African Americans were included in the analysis. Positive family history of prostate cancer was seen in 65 (43%) patients. Preoperative prostate-specific antigen ranged from 0.3 to 52.7 ng/mL (mean = 7.04). The follow-up period ranged from 1 to 123.7 months (mean = 30.3). Biochemical recurrence was encountered in 8 of 151 (5%). ERG overexpression was observed in 85 of 151 (56%) cases, followed by SPINK1 in 61 of 151 (40%), ETV1 in 9 of 149 (6%), and ETV4 in 4 of 141 (3%). There were 25 of 151 (17%) cases showing both ERG and SPINK1 overexpression within different regions of either the same tumor focus or different foci. Higher frequency of ERG overexpression was seen in younger patients (≤45 years old; 76% vs 49%, P = .002), Caucasian men (71% vs 41% P = .0007), organ-confined tumors (64% vs 33%, P = .0008), and tumors of Gleason Grade groups 1 and 2 (62% vs 26%, P = .009). SPINK1 overexpression was more in African American men (68% vs 26%, P = .00008), in tumors with high tumor volume (>20%) and with anterior located tumors. ETV1 and ETV4 demonstrated rare overexpression in these tumors, particularly in the higher-grade tumors. CONCLUSION: This study expands the knowledge of the clonal evolution of multifocal cancer in young patients and support differences in relation to racial background and genetics of prostate cancer.

Pseudogene Associated Recurrent Gene Fusion in Prostate Cancer.

We present the functional characterization of a pseudogene associated recurrent gene fusion in prostate cancer. The fusion gene KLK4-KLKP1 is formed by the fusion of the protein coding gene KLK4 with the noncoding pseudogene KLKP1. Screening of a cohort of 659 patients (380 Caucasian American; 250 African American, and 29 patients from other races) revealed that the KLK4-KLKP1 is expressed in about 32% of prostate cancer patients. Correlative analysis with other ETS gene fusions and SPINK1 revealed a concomitant expression pattern of KLK4-KLKP1 with ERG and a mutually exclusive expression pattern with SPINK1, ETV1, ETV4, and ETV5. Development of an antibody specific to KLK4-KLKP1 fusion protein confirmed the expression of the full-length KLK4-KLKP1 protein in prostate tissues. The in vitro and in vivo functional assays to study the oncogenic properties of KLK4-KLKP1 confirmed its role in cell proliferation, cell invasion, intravasation, and tumor formation. Presence of strong ERG and AR binding sites located at the fusion junction in KLK4-KLKP1 suggests that the fusion gene is regulated by ERG and AR. Correlative analysis of clinical data showed an association of KLK4-KLKP1 with lower preoperative PSA values and in young men (<50 years) with prostate cancer. Screening of patient urine samples showed that KLK4-KLKP1 can be detected noninvasively in urine. Taken together, we present KLK4-KLKP1 as a class of pseudogene associated fusion transcript in cancer with potential applications as a biomarker for routine screening of prostate cancer.

Endovenous Laser Ablation for Treatment of a Partially Thrombosed Proximal Great Saphenous Vein.

INTRODUCTION: Superficial vein thrombosis of the great saphenous vein near to the saphenofemoral junction is generally treated with anticoagulation or surgically. REPORT: We present the case of a 70-year-old man with varicosities and a partially thrombosed great saphenous vein near to the saphenofemoral junction, treated with endovenous laser ablation of the great saphenous vein. DISCUSSION: The case illustrates an alternative treatment option for superficial vein thrombosis of the great saphenous vein, which permits avoiding a prolonged anticoagulation or surgical procedure.

Effect of Vitamin D Supplementation on Markers of Vascular Function: A Systematic Review and Individual Participant Meta-Analysis.

BACKGROUND: Low 25-hydroxyvitamin D levels are associated with an increased risk of cardiovascular events, but the effect of vitamin D supplementation on markers of vascular function associated with major adverse cardiovascular events is unclear. METHODS AND RESULTS: We conducted a systematic review and individual participant meta-analysis to examine the effect of vitamin D supplementation on flow-mediated dilatation of the brachial artery, pulse wave velocity, augmentation index, central blood pressure, microvascular function, and reactive hyperemia index. MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.gov were searched until the end of 2016 without language restrictions. Placebo-controlled randomized trials of at least 4 weeks duration were included. Individual participant data were sought from investigators on included trials. Trial-level meta-analysis was performed using random-effects models; individual participant meta-analyses used a 2-stage analytic strategy, examining effects in prespecified subgroups. 31 trials (2751 participants) were included; 29 trials (2641 participants) contributed data to trial-level meta-analysis, and 24 trials (2051 participants) contributed to individual-participant analyses. Vitamin D3 daily dose equivalents ranged from 900 to 5000 IU; duration was 4 weeks to 12 months. Trial-level meta-analysis showed no significant effect of supplementation on macrovascular measures (flow-mediated dilatation, 0.37% [95% confidence interval, -0.23 to 0.97]; carotid-femoral pulse wave velocity, 0.00 m/s [95% confidence interval, -0.36 to 0.37]); similar results were obtained from individual participant data. Microvascular function showed a modest improvement in trial-level data only. No consistent benefit was observed in subgroup analyses or between different vitamin D analogues. CONCLUSIONS: Vitamin D supplementation had no significant effect on most markers of vascular function in this analysis.

Multicentre observational screening survey for the detection of CTEPH following pulmonary embolism.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a severe complication of pulmonary embolism. Its incidence following pulmonary embolism is debated. Active screening for CTEPH in patients with acute pulmonary embolism is yet to be recommended.This prospective, multicentre, observational study (Multicentre Observational Screening Survey for the Detection of Chronic Thromboembolic Pulmonary Hypertension (CTEPH) Following Pulmonary Embolism (INPUT on PE); ISRCTN61417303) included patients with acute pulmonary embolism from 11 centres in Switzerland from March 2009 to November 2016. Screening for possible CTEPH was performed at 6, 12 and 24 months using a stepwise algorithm that included a dyspnoea phone-based survey, transthoracic echocardiography, right heart catheterisation and radiological confirmation of CTEPH.Out of 1699 patients with pulmonary embolism, 508 patients were assessed for CTEPH screening over 2 years. CTEPH incidence following pulmonary embolism was 3.7 per 1000 patient-years, with a 2-year cumulative incidence of 0.79%. The Swiss pulmonary hypertension registry consulted in December 2016 did not report additional CTEPH cases in these patients. The survey yielded 100% sensitivity and 81.6% specificity. The second step echocardiography in newly dyspnoeic patients showed a negative predictive value of 100%.CTEPH is a rare but treatable disease. A simple and sensitive way for CTEPH screening in patients with acute pulmonary embolism is recommended.

Impact of rivaroxaban on point-of-care assays.

BACKGROUND: Point-of-care testing (POCT) is regularly used to assess haemostasis in various clinical settings. The impact of rivaroxaban on those POCT is still elusive. We aimed to study the effects of rivaroxaban on most commonly used POCT assays. METHODS: Blood samples were taken before, 3h, and 24h after administration of 20mg rivaroxaban to 20 healthy volunteers as part of a prospective, multicenter validation study (clinicaltrials.govNCT01710267). Blood samples were analysed with thromboelastometry (ROTEM®), two platelet function assays (INNOVANCE® PFA-200 and Multiplate®), and the CoaguChek® XS. Rivaroxaban plasma levels were determined using liquid chromatography-mass spectrometry. RESULTS: Rivaroxaban significantly modified some thromboelastometry parameters (CT INTEM: mean difference 56.1s, 95% CI: 41.8, 70.3; CT EXTEM: 47.5s, 95% CI: 37.8, 57.1; CT HEPTEM: 50.1s, 95% CI: 34.7, 65.6), and CoaguChek® XS parameters (prothrombin time: mean difference 3.8s, 95% CI: 3.3, 4.2; INR: 0.32, 95% CI: 0.27, 0.38; prothrombin ratio: -36.1%, 95% CI: -32.3, -39.9). CT EXTEM and INR showed a moderate correlation with rivaroxaban plasma levels (r=0.83; 95% CI 0.69, 0.9 and r=0.83; 95% CI 0.70, 0.91, respectively) and a high sensitivity to detect rivaroxaban treatment at peak levels (0.95; 95% CI: 0.76, 1.0 and 0.90, 95% CI 0.70, 0.99, respectively). CONCLUSIONS: Rivaroxaban 20mg treatment significantly alters ROTEM® and CoaguChek® XS parameters. Even though POCT do not allow precise quantification of rivaroxaban plasma concentration, CT EXTEM and CoaguChek XS detect the presence of rivaroxaban at peak level with a high sensitivity.

Adding a newly trained surgeon into a high-volume robotic prostatectomy group: are outcomes compromised?

This study evaluates whether a new staff surgeon early in the learning curve can be integrated into a high-volume robotic practice with an established robotic team and mentorship without compromising robot-assisted radical prostatectomy (RARP) outcomes of the practice. We analyzed outcomes of 3064 patients who underwent RARP from 2007 to 2012 at a high-volume tertiary center by a robotic practice comprising three experienced robotic surgeons (2846 patients) and a newly hired surgeon (218 patients) immediately out of training (residency and oncology fellowship with 2 years of RARP exposure). The new surgeon performed RARP with intraoperative mentorship by the senior surgeons during the first year. Complications, biochemical recurrence (BCR), positive surgical margins rate (PSM), operating time (OR time), estimated blood loss (EBL) for the new and senior surgeons were compared. Multivariable linear, logistic and exact logistic regression adjusting for disease and patient characteristics were performed. On regression analyses, case number was the most significant predictor of decrease in probability of major complications (p = 0.025) and BCR (p = 0.004) for the new surgeon. Increasing case number was not associated with decrease in minor complications, PSM, OR time, or EBL (p > 0.05). Inclusion of the new surgeon's outcomes did not adversely impact outcomes of the practice. In conclusion, a new surgeon joining a high-volume robotic prostatectomy program with an established robotic team and mentorship can progress through the learning curve without compromising overall outcomes of the practice. Our results may be relevant for programs hiring newly trained staff to join an established robotic practice.

Chronic thromboembolic pulmonary hypertension--a diagnostic and therapeutic update.

Chronic thromboembolic pulmonary hypertension (CTEPH), an important cause of severe pulmonary hypertension, is still underdiagnosed, mainly due to the insufficient use of V/Q scannning in patients with pulmonary hypertension. This article reviews the current diagnostic approach and discusses the therapeutic options in this particular form of pulmonary hypertension. Every patient with CTEPH should undergo an evaluation in a specialised centre with experience in pulmonary arterial endarteriectomy (PEA) as the potentially curative surgical technique. Partly unresolved questions regard the status of the recently described percutaneous transluminal pulmonary angioplasty and the best medical treatment in patients with inoperable or recurrent/persistent pulmonary hypertension after PEA.