BioPrev-C - development and validation of a contemporary prostate cancer risk calculator.

Objectives: To develop a novel biopsy prostate cancer (PCa) prevention calculator (BioPrev-C) using data from a prospective cohort all undergoing mpMRI targeted and transperineal template saturation biopsy. Materials and methods: Data of all men who underwent prostate biopsy in our academic tertiary care center between 11/2016 and 10/2019 was prospectively collected. We developed a clinical prediction model for the detection of high-grade PCa (Gleason score ≥7) based on a multivariable logistic regression model incorporating age, PSA, prostate volume, digital rectal examination, family history, previous negative biopsy, 5-alpha-reductase inhibitor use and MRI PI-RADS score. BioPrev-C performance was externally validated in another prospective Swiss cohort and compared with two other PCa risk-calculators (SWOP-RC and PBCG-RC). Results: Of 391 men in the development cohort, 157 (40.2%) were diagnosed with high-grade PCa. Validation of the BioPrev C revealed good discrimination with an area under the curve for high-grade PCa of 0.88 (95% Confidence Interval 0.82-0.93), which was higher compared to the other two risk calculators (0.71 for PBCG and 0.84 for SWOP). The BioPrev-C revealed good calibration in the low-risk range (0 - 0.25) and moderate overestimation in the intermediate risk range (0.25 - 0.75). The PBCG-RC showed good calibration and the SWOP-RC constant underestimation of high-grade PCa over the whole prediction range. Decision curve analyses revealed a clinical net benefit for the BioPrev-C at a clinical meaningful threshold probability range (≥4%), whereas PBCG and SWOP calculators only showed clinical net benefit above a 30% threshold probability. Conclusion: BiopPrev-C is a novel contemporary risk calculator for the prediction of high-grade PCa. External validation of the BioPrev-C revealed relevant clinical benefit, which was superior compared to other well-known risk calculators. The BioPrev-C has the potential to significantly and safely reduce the number of men who should undergo a prostate biopsy.

Evaluation of Proclarix in the diagnostic work-up of prostate cancer.

Objectives: The use of multiparametric magnetic resonance imaging (mpMRI) has been widely adopted in the diagnostic work-up for suspicious prostate cancer (PCa) and is recommended in most current guidelines. However, mpMRI lesions are often indeterminate and/or turn out to be false-positive on prostate biopsy. The aim of this work was to evaluate Proclarix, a biomarker test for the detection of relevant PCa, regarding its diagnostic value in all men before biopsy and in men with indeterminate lesions on mpMRI (PI-RADS 3) during work-up for PCa. Materials and Methods: Men undergoing mpMRI-targeted and systematic biopsy of the prostate were prospectively enrolled. The Proclarix test was evaluated for the detection accuracy of clinically significant PCa (csPCa) defined as Grade Group ≥ 2 and its association to mpMRI results. Further, Proclarix's performance was also tested when adapted to prostate volume (Proclarix density) and performance compared to PSA density (PSAD). Results: A total of 150 men with a median age of 65 years and median PSA of 5.8 ng/mL were included in this study. CsPCa was diagnosed in 65 (43%) men. Proclarix was significantly associated with csPCa and higher PI-RADS score (p < 0.001). At the pre-defined cut-off of 10%, Proclarix's sensitivity for csPCa was 94%, specificity 19%, negative predictive value 80% and positive predictive value 47%. Proclarix density showed the highest AUC for the detection of csPCa of 0.77 (95%CI: 0.69-0.85) compared to PSA, PSAD and Proclarix alone. Proclarix was able to identify all six csPCa in men with PI-RADS 3 lesions (n = 28), whereas PSAD missed two out of six. At optimized cut-offs, Proclarix density outperformed PSAD by potentially avoiding 41% of unnecessary biopsies. Conclusion: Proclarix demonstrates high sensitivity in detecting csPCa but may still result in unnecessary biopsies. However, Proclarix density was able to outperform PSAD and Proclarix and was found to be useful in men with PI-RADS 3 findings by safely avoiding unnecessary biopsies without missing csPCa.

Focal therapy with high-intensity focused ultrasound for prostate cancer: 3-year outcomes from a prospective trial.

OBJECTIVE: To assess the oncological and functional outcomes of focal high-intensity focused ultrasound (HIFU) in treating localised prostate cancer (PCa), a 3-year prospective study was undertaken using periodic post-ablation saturation biopsies. PATIENTS AND METHODS: Men with two or fewer lesions of grade group (GG) ≤3 PCa were eligible for participation. Additional criteria included a prostate-specific antigen (PSA) level of ≤15 ng/mL, clinical T1c-T2, and a life expectancy of ≥10 years. The primary endpoint was failure-free survival (FFS), defined as absence of clinically significant PCa (csPCa) in- or out-of-field on protocol-mandated saturation biopsy, no whole-gland or systemic salvage treatment, PCa metastasis, or PCa-related death. Results are reported using two distinct definitions of csPCa: (i) the presence of any GG ≥2 and (ii) any GG ≥3 or core involvement of ≥6 mm. Secondary endpoints were functional patient-reported outcome measures addressing urinary, sexual, and bowel function. RESULTS: A total of 91 patients were included: six (7%) with GG1 and 85 (93%) with GG ≥2. In all, 83 (91%) underwent at least one follow-up biopsy. Biopsy attendance at 6, 12, and 36 months was 84%, 67%, and 51%, respectively. The FFS at these time points for any GG ≥2 PCa was 79% (95% confidence interval [CI] 80-88%), 57% (95% CI 48-69%) and 44% (95% CI 34-56%), respectively. Using the second definition, FFS were 88% (95% CI 81-95%), 70% (95% CI 61-81%) and 65% (95% CI 55-77%), respectively. The 3-year cancer-specific survival was 100%, and freedom from metastasis was 99%. Magnetic resonance imaging (MRI) (negative predictive value of up to 89%, 95% CI 84-93%) and relative decrease of PSA values (P = 0.4) performed poorly in detecting residual disease. Urinary and bowel assessment returned to baseline questionnaire scores within 3 months. In all, 17 (21%) patients reported meaningful worsening in erectile function. A significant decrease of PCa related anxiety was observed. CONCLUSIONS: Focal HIFU treatment for localised PCa shows excellent functional outcomes with half of the patients remaining cancer-free after 3 years. Whole-gland treatment was avoided in 81%. Early follow-up biopsies are crucial to change or continue the treatment modality at the right time, while the use of MRI and PSA in detecting PCa recurrence is uncertain.

Atherosclerosis of the iliac arteries for the prediction of erectile dysfunction and epistaxis in men undergoing abdominal CT scan.

BACKGROUND: To investigate the association between erectile dysfunction (ED) as well as epistaxis (ES) in relation to the extent of iliac atherosclerosis. METHODS: In this retrospective cross-sectional study, all consecutive male patients treated at our institution from 01/2016 to 12/2020 undergoing abdominal CT scan were evaluated. Patients (n = 1272) were invited by mail to participate in the study in returning two questionnaires for the evaluation of ED (IIEF-5) and ES. Patients who returned filled-in questionnaires within a 3-month deadline were included in the study. The extent of atherosclerosis in the common iliac artery (CIA) and the internal iliac artery (IIA) was assessed by calcium scoring on unenhanced CT. Stratification of results was performed according to reported IIEF-5 scores and consequential ED groups. RESULTS: In total, 437 patients (34.4% of contacted) met the inclusion criteria. Forty-two patients did not fulfill predefined age requirements (< 75 years) and 120 patients had to be excluded as calcium scoring on nonenhanced CT was not feasible. Finally, 275 patients were included in the analysis and stratified into groups of "no-mild" (n = 146) and "moderate-severe" (n = 129) ED. The calcium score (r=-0.28, p < 0.001) and the number of atherosclerotic lesions (r=-0.32, p < 0.001) in the CIA + IIA showed a significant negative correlation to the IIEF-5 score, respectively. Patients differed significantly in CIA + IIA calcium score (difference: 167.4, p < 0.001) and number of atherosclerotic lesions (difference: 5.00, p < 0.001) when belonging to the "no-mild" vs. "moderate-severe" ED group, respectively. A multivariable regression model, after adjusting for relevant baseline characteristics, showed that the number of atherosclerotic CIA + IIA lesions was an independent predictor of ED (OR = 1.05, p = 0.036), whereas CIA + IIA calcium score was not (OR = 1.00031, p = 0.20). No relevant correlation was found between ES episodes and IIEF-5 scores (r=-0.069, p = 0.25), CIA + IIA calcium score (r=-0.10, p = 0.87) or number of atherosclerotic CIA + IIA lesions (r=-0.032, p = 0.60), respectively. CONCLUSIONS: The number of atherosclerotic lesions in the iliac arteries on nonenhanced abdominal CT scans is associated with the severity of ED. This may be used to identify subclinical cardiovascular disease and to quantify the risk for cardiovascular hazards in the future. TRIAL REGISTRATION: BASEC-Nr. 2020 - 01637.

Stress Urinary Incontinence: An Unsolved Clinical Challenge.

Stress urinary incontinence is still a frequent problem for women and men, which leads to pronounced impairment of the quality of life and withdrawal from the social environment. Modern diagnostics and therapy improved the situation for individuals affected. But there are still limits, including the correct diagnosis of incontinence and its pathophysiology, as well as the therapeutic algorithms. In most cases, patients are treated with a first-line regimen of drugs, possibly in combination with specific exercises and electrophysiological stimulation. When conservative options are exhausted, minimally invasive surgical therapies are indicated. However, standard surgeries, especially the application of implants, do not pursue any causal therapy. Non-absorbable meshes and ligaments have fallen into disrepute due to complications. In numerous countries, classic techniques such as colposuspension have been revived to avoid implants. Except for tapes in the treatment of stress urinary incontinence in women, the literature on randomized controlled studies is insufficient. This review provides an update on pharmacological and surgical treatment options for stress urinary incontinence; it highlights limitations and formulates wishes for the future from a clinical perspective.

Improved Prostate-Specific Membrane Antigen (PSMA) Stimulation Using a Super Additive Effect of Dutasteride and Lovastatin In Vitro.

Prostate-specific membrane antigen (PSMA)-based imaging improved the detection of primary, recurrent and metastatic prostate cancer. However, in certain patients, a low PSMA surface expression can be a limitation for this promising diagnostic tool. Pharmacological induction of PSMA might be useful to further improve the detection rate of PSMA-based imaging. To achieve this, we tested dutasteride (Duta)-generally used for treatment of benign prostatic enlargement-and lovastatin (Lova)-a compound used to reduce blood lipid concentrations. We aimed to compare the individual effects of Duta and Lova on cell proliferation as well as PSMA expression. In addition, we tested if a combination treatment using lower concentrations of Duta and Lova can further induce PSMA expression. Our results show that a treatment with ≤1 µM Duta and ≥1 µM Lova lead to a significant upregulation of whole and cell surface PSMA expression in LNCaP, C4-2 and VCaP cells. Lower concentrations of Duta and Lova in combination (0.5 µM Duta + 0.5 µM Lova or 0.5 µM Duta + 1 µM Lova) were further capable of enhancing PSMA protein expression compared to a single compound treatment using higher concentrations in all tested cell lines (LNCaP, C4-2 and VCaP).

Transurethral injection of autologous muscle precursor cells for treatment of female stress urinary incontinence: a prospective phase I clinical trial.

INTRODUCTION AND HYPOTHESIS: The purpose was to investigate the safety and feasibility of transurethral injections of autologous muscle precursor cells (MPCs) into the external urinary sphincter (EUS) to treat stress urinary incontinence (SUI) in female patients. METHODS: Prospective and randomised phase I clinical trial. Standardised 1-h pad test, International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF), urodynamic study, and MRI of the pelvis were performed at baseline and 6 months after treatment. MPCs gained through open muscle biopsy were transported to a GMP facility for processing and cell expansion. The final product was injected into the EUS via a transurethral ultrasound-guided route. Primary outcomes were defined as any adverse events (AEs) during follow-up. Secondary outcomes were functional, questionnaire, and radiological results. RESULTS: Ten female patients with SUI grades I-II were included in the study and 9 received treatment. Out of 8 AEs, 3 (37.5%) were potentially related to treatment and treated conservatively: 1 urinary tract infection healed with antibiotics treatment, 1 dysuria and 1 discomfort at biopsy site. Functional urethral length under stress was 25 mm at baseline compared with 30 mm at 6 months' follow-up (p=0.009). ICIQ-UI-SF scores improved from 7 points at baseline to 4 points at follow-up (p=0.035). MRI of the pelvis revealed no evidence of tumour or necrosis, whereas the diameter of the EUS muscle increased from 1.8 mm at baseline to 1.9 mm at follow-up (p=0.009). CONCLUSION: Transurethral injections of autologous MPCs into the EUS for treatment of SUI in female patients can be regarded as safe and feasible. Only a minimal number of expected and easily treatable AEs were documented.

Index lesion contouring on prostate MRI for targeted MRI/US fusion biopsy - Evaluation of mismatch between radiologists and urologists.

PURPOSE: Mistargeting of focal lesions due to inaccurate segmentations can lead to false-negative findings on MRI-guided targeted biopsies. The purpose of this retrospective study was to examine inter-reader agreement of prostate index lesion segmentations from actual biopsy data between urologists and radiologists. METHOD: Consecutive patients undergoing transperineal MRI-targeted prostate biopsy for PI-RADS 3-5 lesions between January 2020 and December 2021 were included. Agreement between segmentations on T2w-images between urologists and radiologists was assessed with Dice similarity coefficient (DSC) and 95 % Hausdorff distance (95 % HD). Differences in similarity scores were compared using Wilcoxon test. Differences depending on lesion features (size, zonal location, PI-RADS scores, lesion distinctness) were tested with Mann-Whitney U test. Correlation with prostate signal-intensity homogeneity score (PSHS) and lesion size was tested with Spearman's rank correlation. RESULTS: Ninety-three patients (mean age 64.9 ± 7.1y, median serum PSA 6.5 [4.33-10.00]) were included. Mean similarity scores were statistically significantly lower between urologists and radiologists compared to radiologists only (DSC 0.41 ± 0.24 vs. 0.59 ± 0.23, p < 0.01; 95 %HD 6.38 ± 5.45 mm vs. 4.47 ± 4.12 mm, p < 0.01). There was a moderate and strong positive correlation between DSC scores and lesion size for segmentations from urologists and radiologists (ρ = 0.331, p = 0.002) and radiologists only (ρ = 0.501, p < 0.001). Similarity scores were worse in lesions ≤ 10 mm while other lesion features did not significantly influence similarity scores. CONCLUSION: There is significant mismatch of prostate index lesion segmentations between urologists and radiologists. Segmentation agreement positively correlates with lesion size. PI-RADS scores, zonal location, lesion distinctness, and PSHS show no significant impact on segmentation agreement. These findings could underpin benefits of perilesional biopsies.

Therapy decisions after diagnosis of prostate cancer in men with negative prostate MRI.

BACKGROUND: To investigate the clinical implications of magnetic resonance imaging (MRI) negative prostate cancer (PCa) in a cohort of men undergoing transperineal prostate biopsy. METHODS: We included all men without prior diagnosis of PCa undergoing transperineal template saturation ± fusion-guided targeted biopsy of the prostate between November 2014 and March 2018. Before biopsy, all patients underwent MRI and biopsies were performed irrespective of imaging results. Baseline characteristics, imaging, biopsy results, and follow-up information were retrieved from the patient charts. Patients were classified as either MRI negative (Prostate Imaging Reporting and Data System [PIRADS] ≤ 2) or positive (PIRADS ≥ 3). ISUP grade group 1 was defined as clinically nonsignificant (nsPCa) and ≥2 as clinically significant PCa (csPCa). Primary outcome was the individual therapeutic decision after diagnosis of PCa stratified according to MRI visibility. Secondary outcomes were the sensitivity and specificity of MRI, and the urooncological outcomes after radical prostatectomy (RP). RESULTS: From 515 patients undergoing prostate biopsy, 171 (33.2%) patients had a negative and 344 (66.8%) a positive MRI. Pathology review stratified for MRI negative and positive cases revealed nsPCa in 27 (15.8%) and 32 (9.3%) and csPCa in 26 (15.2%) and 194 (56.4%) of the patients, respectively. The rate of active treatment in the MRI negative was lower compared with the MRI positive cohort (12.3% vs. 53.2%; odd ratio [OR] = 0.12; p < 0.001). While men with negative MRI were more likely to undergo active surveillance (AS) than MRI positive patients (18.1% vs. 10.8%; OR = 1.84; p = 0.027), they rarely underwent RP (6.4% vs. 40.7%, OR = 0.10; p < 0.001). Logistic regression revealed that a negative MRI was independently protective for active treatment (OR = 0.32, p = 0.014). The specificity, sensitivity, negative, and positive predictive value of MRI for detection of csPCa were 49.2%, 88.2%, 56.4%, and 84.8%, respectively. The rate of adverse clinicopathological outcome features (pT3/4, ISUP ≥4, or prostate-specific antigen [PSA]-persistence) following RP was 4.7% for men with MRI negative compared to 17.4% for men with MRI positive PCa (OR = 3.1, p = 0.19). CONCLUSION: Only few men with MRI negative PCa need active cancer treatment at the time of diagnosis, while the majority opts for AS. Omitting prostate biopsies and performing a follow-up MRI may be a safe alternative to reduce the number of unnecessary interventions.

Long-Term Oncological Efficacy of Retroperitoneoscopic Radical Nephrectomy of Localized Renal Cell Cancer pT1-3 (≤12 cm).

.

Erectile dysfunction and penile rehabilitation after pelvic fracture: a systematic review and meta-analysis.

OBJECTIVE: To investigate the rate of erectile dysfunction (ED) after pelvic ring fracture (PRF). DESIGN: Systematic review and meta-analysis. METHODS: A systematic literature search of the Cochrane, EMBASE, MEDLINE, Scopus and Web of Science Library databases was conducted in January 2020. Included were original studies performed on humans assessing ED after PRF according to the 5-item International Index of Erectile Function (IIEF-5) questionnaire and fracture classification following Young and Burgess, Tile or Arbeitsgemeinschaft für Osteosynthesefragen/Orthopedic Trauma Association. Furthermore, interventional cohort studies assessing the effect of penile rehabilitation therapy with phosphodiesterase-5-inhibitors (PDE-5-I) on IIEF-5 scores compared before and after treatment were included. Results were presented as forest plots of proportions of patients with ED after PRF or mean changes on IIEF-5 questionnaires before and after penile rehabilitation. Studies not included in the quantitative analysis were narratively summarised. Risk of bias assessment was conducted using the revised tool for the Quality Assessment on Diagnostic Accuracy Studies. RESULTS: The systematic literature search retrieved 617 articles. Seven articles were included in the qualitative analysis and the meta-analysis. Pooled proportions revealed 37% of patients with ED after suffering any form of PRF (result on probability scale pr=0.37, 95% CI: 0.26 to 0.50). Patients after 3 months of penile rehabilitation therapy reported a higher IIEF-5 score than before (change score=6.5 points, 95% CI: 2.54 to 10.46, p value=0.0013). CONCLUSION: Despite some heterogeneity and limited high-quality research, this study concludes that patients suffering from any type of PRF have an increased risk of developing ED. Oral intake of PDE-5-I for the purpose of penile rehabilitation therapy increases IIEF-5 scores and may relevantly influence quality-of-life in these patients. PROSPERO REGISTRATION NUMBER: CRD42020169699.

Treatment of Stress Urinary Incontinence with Muscle Stem Cells and Stem Cell Components: Chances, Challenges and Future Prospects.

Urinary incontinence (UI) is a major problem in health care and more than 400 million people worldwide suffer from involuntary loss of urine. With an increase in the aging population, UI is likely to become even more prominent over the next decades and the economic burden is substantial. Among the different subtypes of UI, stress urinary incontinence (SUI) is the most prevalent and focus of this review. The main underlying causes for SUI are pregnancy and childbirth, accidents with direct trauma to the pelvis or medical treatments that affect the pelvic floor, such as surgery or irradiation. Conservative approaches for the treatment of SUI are pelvic physiotherapy, behavioral and lifestyle changes, and the use of pessaries. Current surgical treatment options include slings, colposuspensions, bulking agents and artificial urinary sphincters. These treatments have limitations with effectiveness and bear the risk of long-term side effects. Furthermore, surgical options do not treat the underlying pathophysiological causes of SUI. Thus, there is an urgent need for alternative treatments, which are effective, minimally invasive and have only a limited risk for adverse effects. Regenerative medicine is an emerging field, focusing on the repair, replacement or regeneration of human tissues and organs using precursor cells and their components. This article critically reviews recent advances in the therapeutic strategies for the management of SUI and outlines future possibilities and challenges.

Value of an online PI-RADS v2.1 score calculator for assessment of prostate MRI.

PURPOSE: To evaluate the value of a browser-based PI-RADS Score Calculator (PCalc) compared to MRI reporting using the official PI-RADS v2.1 document (PDoc) for non-specialized radiologists in terms of reporting efficiency, interrater agreement and diagnostic accuracy for detection of clinically significant prostate cancer (PCa). METHODS: Between 09/2013 and 04/2015, 100 patients (median age, 64.8; range 47.5-78.2) who underwent prostate-MRI at a 3 T scanner and who received transperineal prostate mapping biopsy within <6 months were included in this retrospective study. Two non-specialized radiology residents (R1, R2) attributed a PI-RADS version 2.1 score for the most suspect (i. e. index) lesion (i) using the original PI-RADS v2.1 document only and after a 6-week interval (ii) using a browser-based PCalc. Reading time was measured. Reading time differences were assessed using Wilcoxon signed rank test. Intraclass-correlation Coefficient (ICC) was used to assess interrater agreement (IRA). Parameters of diagnostic accuracy and ROC curves were used for assessment of lesion-based diagnostic accuracy. RESULTS: Cumulative reading time was 32:55 (mm:ss) faster when using the PCalc, the difference being statistically significant for both readers (p < 0.05). The difference in IRA between the image sets (ICC 0.55 [0.40, 0.68]) and 0.75 [0.65, 0.82] for the image set with PDoc and PCalc, respectively) was not statistically significant. There was no statistically significant difference in lesion-based diagnostic accuracy (AUC 0.83 [0.74, 0.92] and 0.82 [95 %CI: 0.74, 0.91]) for images assessed with PDoc as compared to PCalc (AUC 0.82 [0.74, 0.91] and 0.74 [95 %CI: 0.64, 0.83]) for R1 and R2, respectively. CONCLUSION: Non-specialized radiologists may increase reading speed in prostate MRI with the help of a browser-based PI-RADS Score Calculator compared to reporting using the official PI-RADS v2.1 document without impairing interreader agreement or lesion-based diagnostic accuracy for detection of clinically significant PCa.

Dynamic contrast enhancement in prostate MRI as predictor of erectile function and recovery after radical prostatectomy.

PURPOSE: To analyze routine preoperative prostate MRI to predict erectile function (EF) before and after radical prostatectomy (RP). METHODS: Patients who underwent RP with an existing preoperative MRI including dynamic contrast-enhanced images and completed International Index of Erectile Function (IIEF-5) questionnaires at baseline and 12 months postoperative. They were divided into four erectile dysfunction (ED) groups according to preoperative IIEF-5 score. The perfusion quality was measured in the peripheral zone of the prostate by the ratio of signal increase 120 s after wash-in of contrast agent (Ratio120) in preoperative MRI and compared between the ED groups. RESULTS: Ratio120 showed differences among the preoperative ED groups (p = .020) in 97 patients. According to IIEF-5 at 12 months postoperative, 43 patients were dichotomized into "no to mild" (≥17 points) and "moderate to severe" (≤16) ED groups. Ratio120 revealed differences among the postoperative ED groups (128.84% vs. 101.95%; p = .029) and stayed an independent predictor for ED in the multivariable regression analysis (adjusted for age, nerve-sparing and preoperative IIEF-5). ROC curves demonstrated an additional diagnostic benefit. CONCLUSIONS: Preoperative MRI of the prostate may be used for the prediction of EF and postsurgical recovery after RP. This may serve as important tool in preoperative patient counseling and management of expectations.

Feasibility, technique and accuracy of ultrasound-guided transurethral injections into the urinary sphincter of female cadavers: proof of concept.

BACKGROUND: The injection of muscle precursor cells (MPC) into the external urinary sphincter muscle (EUS) is a promising therapeutic option for regenerative treatment of stress urinary incontinence (SUI). The objective of the present project was to conduct a pre-clinical trial to investigate the feasibility and accuracy of ultrasound (US) guided, transurethral injections into the EUS of female cadavers. METHODS: This is a prospective, anatomical, interventional and radiological cadaveric laboratory investigation. Two urologists performed transurethral US-guided injections to deliver nano-iron particles into the EUS. The intervention was performed in three unfixed, fresh female cadavers. Each cadaver received MRI before and CT as well as MRI of the pelvis after the injections. RESULTS: The precision and accumulation of nano-iron particles in the EUS was compared using a rating scale to evaluate left versus right and anterior versus posterior distribution in axial and sagittal orientation with US, MRI and CT. The accuracy of our US-guided injections into the anterior target region yielded 4 points on the rating scale. Adequate precision and accumulation of particles in the left versus right EUS were also demonstrated (3 vs. 3.33 points, respectively). Signal intensity in MRI revealed a mean ratio of 0.33 before and after injection. CT scans showed no relevant artefacts impairing the assessment. CONCLUSION: US-guided, transurethral injection into the EUS is feasible and imaging reveals a precise accumulation in the target region. Our method provides an appropriate approach to deliver MPC in the EUS muscle for a regenerative treatment of SUI in the near future.

Evaluation of Urinary Sphincter Function by Rapid Magnetic Resonance Diffusion Tensor Imaging.

PURPOSE: This study aimed to assess the feasibility of a rapid diffusion tensor imaging (DTI) for evaluation of the female urinary sphincter function based on differentiation between rest and muscle contraction. METHODS: Magnetic resonance imaging (MRI) of the lower pelvis was performed at 3 Tesla in 10 healthy female volunteers (21-36 years; body mass index, 20.8±3.6 kg/m2) between June and July 2019. High-resolution T1- and T2-weighted images were acquired for anatomical reference, and following DTI performed in 4 experiment phases: twice during rest (denoted rest-1, rest-2) and contraction (contraction-1, contraction-2). Manual segmentation of the urinary sphincter and the levator ani muscles were performed by 2 independent readers. Mean diffusivity (MD) and fractional anisotropy (FA) values derived from DTI volumes were compared in search for significant differences between the experiment phases. Interreader agreement was assessed by intraclass correlation coefficient (ICC). RESULTS: Kruskal-Wallis test showed significant differences between MD values among all the experiment phases, by both independent readers (1st: X2 [3,76]=17.16, P<0.001 and 2nd: X2 [3,76]=15.88, P<0.01). Post hoc analysis revealed differences in MD values by both readers between: rest-1 vs. contraction-1 (least P<0.05), rest-1 vs. contraction-2 (P<0.01), rest-2 vs. contraction-1 (P<0.03), rest-2 vs. contraction-2 (P=0.02) with overall mean 'rest' to 'contraction' ΔMD=20.6%. No MD or FA differences were found between rest-1 vs. rest-2 and contraction-1 vs. contraction-2 among all the experiment phases, and interreader agreement was ICC=0.85 (MD) and ICC=0.79 (FA). CONCLUSION: Rapid DTI might prospectively act as a supporting tool for the evaluation of female pelvic floor muscle function, and incontinence assessment.

Contrast media kinetics in multiparametric magnetic resonance imaging before radical prostatectomy predicts the probability of postoperative incontinence.

PURPOSE: To evaluate the role of preoperative multiparametric magnetic resonance imaging (MRI) as predictor of post-prostatectomy incontinence (PPI). METHODS: We analyzed patients who underwent robot-assisted radical prostatectomy for localized prostate cancer at our institution between July 2015 and April 2017. In these patients, we measured the perfusion quality of the pelvic floor with contrast media kinetics in the preoperative MRI of the prostate and compared the levator ani muscle (region of interest) to the surrounding pelvic muscle structures (reference). Prospectively collected questionnaires regarding urinary incontinence were then evaluated 1 year postoperatively. Outcomes were dichotomized into "continent" (ICIQ-Score = 0-5) and "incontinent" (ICIQ-Score ≥ 6). In each patient, we determined the perfusion ratio of the levator ani muscle divided by the surrounding pelvic muscle structures and compared them among the groups. RESULTS: Forty-two patients were included in the study (n = 22 in "continent", n = 20 in "incontinent" group). The median perfusion ratio from the continent group was significantly higher compared to the incontinent group (1.61 vs. 1.15; 95% CI 0.09-0.81, p = 0.015). The median perfusion ratio in "excellent" (ICIQ-Score = 0) was significantly higher than in "poor" (ICIQ-Score ≥ 11) outcomes (1.48 vs. 0.94; 95% CI 0.04-1.03, p = 0.036). Further, a higher perfusion ratio was negatively correlated with ICIQ-Score (r = - 0.33; 95% CI - 0.58 to 0.03; p = 0.031). CONCLUSIONS: Our data demonstrate a promising new strategy to predict PPI through the perfusion quality of pelvic muscle structures with contrast media kinetics. This may facilitate preoperative patient consulting and decision-making.

Increased in vivo patellofemoral loading after total knee arthroplasty in resurfaced patellae.

PURPOSE: The primary purpose of the study was to investigate if and how patellar bone tracer uptake (BTU) distribution in SPECT/CT is influenced by patellar resurfacing and the position of femoral and tibial TKA component position. METHODS: A total of 104 knees of 103 consecutive patients who underwent primary TKA were prospectively investigated. Primary patellar resurfacing was done in 40 knees while 64 had a TKA without patellar resurfacing. All patients underwent clinical assessment using the knee society score (KSS) and standardized radiographs and Tc-99m-HDP-SPECT/CT before and 12 and 24 months after TKA. Measurements of BTU including intensity and anatomical distribution pattern in eight different patellar regions were performed. Tibial and femoral TKA component position was assessed from 3D reconstructed CT data. Patellar height, thickness and tilt were measured and the distance between the tibial tuberosity and the trochlear groove (TT-TG) was measured. Univariate analysis was performed to identify differences between the two groups (p < 0.05). RESULTS: Significantly higher BTU was found in the anterior, non-articular, areas of the patella in patients who underwent patellar resurfacing (p < 0.05). The BTU pattern was similar between the groups, as the maximal uptake in both groups was seen in the superior posterior parts and the minimal uptake was seen in the inferior anterior parts. The mean postoperative KSS was significantly higher in the unresurfaced group after 12 months (p < 0.05), but with no significant difference after 24 months. CONCLUSIONS: Based on the findings of the present study, patellar resurfacing is related to significantly higher BTU in the anterior parts of the patella and lower clinical outcomes. In light of these results, routine patellar resurfacing as part of a primary TKA might be reevaluated. SPECT/CT enables a precise localization of the BTU and might be considered as the ideal imaging modality for evaluation and investigate of patellofemoral disorders after TKA.

Coronal femoral TKA position significantly influences in vivo patellar loading in unresurfaced patellae after primary total knee arthroplasty.

PURPOSE: As patellar tracking and loading is influenced by tibial tuberosity and trochlear groove (TT-TG) distance, patellar height, thickness and tilt as well as TKA component position, it was our hypothesis that these parameters significantly correlate with patellar BTU intensity and localization in SPECT/CT. The purpose of the study was to investigate whether TKA component position as well as the height, thickness and tilt of the unresurfaced patella influences the intensity and the distribution pattern of BTU in SPECT/CT. METHODS: A total of 62 consecutive patients who underwent primary TKA without patellar resurfacing were prospectively included. Demographic data such as age, gender, side and type of primary TKA were noted. All patients underwent clinical and radiological examination in a specialized knee clinic, including standardized radiographs (anterior-posterior and lateral weight bearing, patellar skyline view) and Tc-99m-HDP-SPECT/CT before, 12 and 24 months after TKA. SPECT/CT images were analysed on 3D reconstructed images. Rotational, sagittal and coronal position of the tibial and femoral TKA components was assessed using a previously validated analysis software. Measurements of BTU including intensity and anatomical distribution pattern were also performed from 3D data. The patellar height, thickness and tilt were measured, and the distance between TT and TG was measured using axial CT images. Univariate analysis was performed to identify any correlations between BTU and TKA component position and patellar measurements (p < 0.05). RESULTS: The highest median BTU was measured in the superior posterior parts of the patella. A statistically significant correlation was found between valgus alignment of the femoral TKA and increased BTU at the lateral patellar regions (p < 0.05). External rotation of the tibial TKA correlated with increased BTU at the lateral superior joint adjacent part (p < 0.05). No correlation was found between the tibial TKA position (varus-valgus, anterior and posterior slope), TT-TG distance, patellar height and patellar BTU values. CONCLUSIONS: A significant correlation of increased patellar BTU was found with femoral valgus TKA alignment. These findings highlight the importance of femoral TKA position in coronal plane with regard to post-operative patellar tracking. Moreover, these facts might explain anterior knee pain in unhappy TKA with femoral valgus alignment. LEVEL OF EVIDENCE: Diagnostic study, Level II.

Prognostic value of long-term blood pressure changes in patients with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is the final stage of many heart diseases. To improve outcomes, important risk factors for adverse clinical events in the CHF population need to be identified. The aim of the present study was to delineate the influence of long-term blood pressure (BP) changes on prognosis and mortality in a real-world cohort of CHF patients. METHODS AND RESULTS: This is a retrospective longitudinal analysis. Repeated office BP measurements were scheduled during follow-up visits every 3-6 months. The primary endpoint was time to death or heart transplantation (HTx). A Cox regression with time-dependent strata was used to analyse the effect of systolic BP (SBP) values and its change during follow-up on the primary endpoint. A total of 927 patients presented with a median survival of 7.7 [95% confidence interval (CI) 6.6-9.8] years. During follow-up, 220 patients died and 70 patients underwent HTx. The BP stratum with the most stable values showed the best survival. Blood pressure changes with an increase or decrease greater than ±10 mmHg per year led to a significantly worse outcome [hazard ratio (HR) 1.8 and 2.0, respectively]. The stratum with the lowest SBP levels (<90 mmHg) had the highest mortality. Multiple regression analysis showed a HR factor of 17 (95% CI 9.7-29) in comparison with the stratum with SBP ≥130 mmHg. CONCLUSION: Low SBP (<90 mmHg) and pronounced long-term changes in SBP were associated with poor survival in patients with CHF. Additional prospective studies are warranted to further specify optimal BP targets in patients with CHF.