Illumination matters part IV: blackout and whiteout in flexible ureteroscopy - first report on a phenomenon observed by PEARLS.

PURPOSE: To date, no study has evaluated effects of varying brightness settings on image quality from flexible ureteroscopes submerged in saline. The aim was to evaluate blackout and whiteout occurrences in an in-vitro kidney calyx model. MATERIAL AND METHODS: We evaluated a series of contemporary flexible ureteroscopes including the Storz Flex-Xc and Flex-X2s, Olympus V3 and P7, Pusen 7.5F and 9.2F, as well as OTU WiScope using a 3D-printed enclosed pink in-vitro kidney calyx model submerged in saline. Endoscopic images were captured with ureteroscope tip placed at 5 mm,10 mm and 20 mm distances. The complete range of brightness settings and video capture modes were evaluated for each scope. Distribution of brightness on a grayscale histogram of images was analyzed (scale range 0 to 255). Blackout and whiteout were defined as median histogram ranges from 0 to 35 and 220 to 255, respectively (monitor image too dark or too bright for the human eye, respectively). RESULTS: Blackout occurred with the P7, Pusen 7.5F, 9.2F and WiScope at all distances, and V3 at 20 mm - with lowest brightness settings. Whiteout occurred with Flex-X2s, V3 and P7 at 5 mm and 10 mm, as well as with V3 and P7 at 20 mm - mostly with highest brightness settings. The Flex-Xc had neither blackout nor whiteout at all settings and distances. CONCLUSION: Blackout or whiteout of images is an undesirable property that was found for several scopes, possibly impacting diagnostic and therapeutic purposes during ureteroscopy. These observations form a guide to impact a urologist's choice of instruments and settings.

Illumination matters Part II: advanced comparative analysis of flexible ureteroscopes in a kidney model by PEARLS.

PURPOSE: The aim of the study was to evaluate illumination properties in an in-vitro kidney calyx model in saline. DESIGN AND METHODS: We evaluated a series of contemporary flexible ureteroscopes including the Storz Flex-Xc and Flex-X2s, Olympus V3 and P7, Pusen 7.5F and 9.2F, as well as OTU WiScope using a 3D-printed closed pink kidney calyx model, submerged in saline. A spectrometer was used for illuminance and color temperature measurements at different openings located at center (direct light), 45° (direct and indirect light) and 90°(indirect light) to the axis of the scope. RESULTS: Maximum illuminance was at the center opening for all scopes (range: 284 to 12,058 lx at 50% brightness and 454 to 11,871 lx at 100% brightness settings). The scope with the highest center illuminance (Flex-Xc) was 26 times superior to the scope with the lowest illuminance (Pusen 7.5Fr) at 100% brightness setting. For each scope, there was a peripheral illuminance drop ranging from - 43 to - 92% at 50% brightness and - 43% to - 88% at 100% brightness settings, respectively (all p < 0.01). Highest drop was for the P7 and the Pusen 9.2F. All scopes had illuminance skew, except the V3. All scopes had a warm color temperature. CONCLUSION: Illumination properties vary between ureteroscopes in an enclosed cavity in saline, and differs at center vs 45° and 90° positions within scopes. Peripheral illuminance drop can be as high as - 92%, which is undesirable. This may affect the choice of ureteroscope and light brightness settings used in surgery by urologists.

Illumination matters part I: comparative analysis of light sources and illumination in flexible ureteroscopy-fundamental findings from a PEARLS analysis.

PURPOSE: Illumination characteristics of flexible ureteroscopes have been evaluated in air, but not in saline, the native operative medium for endourology. The aim was to evaluate light properties of contemporary ureteroscopes in air versus saline, light distribution analysis, and color temperature. METHODS: We evaluated the Storz Flex-Xc and Flex-X2s, Olympus V3 and P7, Pusen 7.5F and 9.2F, and OTU WiScope using a 3D printed black target board in-vitro model submerged in saline. A spectrometer was used for lux and color temperature measurements at different opening locations. RESULTS: Illuminance was higher in saline compared to air (5679 vs. 5205 lx with Flex-Xc, p = 0.02). Illuminance in saline differed between ureteroscopes (ANOVA p < 0.001), with highest for the Flex-Xc at 100% brightness setting (5679 lx), followed by Pusen 9.2F (5280 lx), Flex-X2s (4613 lx), P7 (4371 lx), V3 (2374 lx), WiScope (582 lx) and finally Pusen 7.5F (255 lx). The same ranking was found at 50% brightness setting, with the highest ureteroscope illuminance value 34 times that of the scope with lowest illuminance. Most scopes had maximum illuminance off center, with skewness. Three scopes had two light sources, with one light source for all other scopes. Inter-scope comparisons revealed significant differences of color temperature (ANOVA p < 0.001). CONCLUSION: The study demonstrates the presence of inhomogeneous light spread as well as large differences in illumination properties of ureteroscopes, possibly impacting on the performance of individual scopes in vivo. Additionally, the study suggests that future studies on illumination characteristics of flexible ureteroscopes should ideally be done in saline, and no longer in air.

Ustekinumab for pyoderma gangrenosum-like skin ulcerations in late-onset leukocyte adhesion deficiency.

Background: Leukocyte adhesion deficiency type 1 (LAD-1) is a congenital immunodeficiency leading to impaired trafficking of neutrophils to inflammation sites. Solitary or multiple pyoderma gangrenosum (PG)-like skin ulcers (PGLUs) have been reported previously in 13 children (aged 0.5-19 years) with LAD-1. Objective: Our aim was to report the case of a 10-year-old boy presenting with PGLUs as the first manifestation of LAD-1 treated with ustekinumab. Methods: We obtained in situ cytokine profiles. Results: PGLUs were triggered by cutaneous ringworm infection (Trichophyton tonsurans). Skin biopsy samples showed increased intralesional expression of IL-17A, Il-23, and IL-1ß as compared with their expression in healthy controls. After an unsuccessful attempt at treatment with oral methylprednisolone, ustekinumab induced regression of the ulcerations, associated with complete normalization of the cytokine profile. Conclusions: PGLUs, triggered by ringworm infection, can be a late harbinger of LAD-1. Ustekinumab is a safe and effective therapeutic option for patients with LAD-1 and PGLUs while bridging the time until stem cell transplantation.

Illumination matters Part III: Impact of light obstruction on illuminance from flexible ureteroscopes - a comparative PEARLS analysis.

PURPOSE: Artifacts from poor ureteroscopes' light design with shadowing and dark areas in the field of view have been reported. The aim was to quantify effects of light obstruction in a kidney calyx model. METHODS: We evaluated a series of contemporary flexible ureteroscopes including the Storz Flex-Xc and Flex-X2s, Olympus V3 and P7, Pusen 7.5F and 9.2F, as well as OTU Wiscope using an enclosed 3D-printed pink in vitro kidney calyx model submerged in saline, where the field of light was intentionally partially obstructed alternatively at 12, 3, 6, and 9 o'clock. A color spectrometer was used for illuminance measurements at a 45° opening position in the background of the model. RESULTS: Overall and mean background illuminance for each obstructive situation were significantly different between scopes for both 50% and 100% brightness settings (ANOVA p < 0.001). At 50% brightness setting, almost all scopes had their highest and lowest background illuminance with the 6 o'clock and 3 o'clock obstructive situation, respectively. At 100% brightness setting, these became 6 o'clock and 12 o'clock obstructive situations. Considering each obstructive situation individually, the Flex-Xc was consistently the scope with highest background illuminance and the Pusen 7.5F the lowest. Background illuminance for each obstructive situation varied significantly for each scope individually, with the greatest range of variability for Pusen 7.5F and V3. CONCLUSIONS: Illuminance performance of ureteroscopes within an obstructed calyx model differ significantly for various obstructive situations. Urologists should be aware of this to help guide their choice of ureteroscope.

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.

Cascading events during the 1650 tsunamigenic eruption of Kolumbo volcano.

Volcanic eruptions can trigger tsunamis, which may cause significant damage to coastal communities and infrastructure. Tsunami generation during volcanic eruptions is complex and often due to a combination of processes. The 1650 eruption of the Kolumbo submarine volcano triggered a tsunami causing major destruction on surrounding islands in the Aegean Sea. However, the source mechanisms behind the tsunami have been disputed due to difficulties in sampling and imaging submarine volcanoes. Here we show, based on three-dimensional seismic data, that ~1.2 km³ of Kolumbo's northwestern flank moved 500-1000 m downslope along a basal detachment surface. This movement is consistent with depressurization of the magma feeding system, causing a catastrophic explosion. Numerical tsunami simulations indicate that only the combination of flank movement followed by an explosive eruption can explain historical eyewitness accounts. This cascading sequence of natural hazards suggests that assessing submarine flank movements is critical for early warning of volcanogenic tsunamis.

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.

Pulsed Thulium:YAG laser - What is the lithotripsy ablation efficiency for stone dust from human urinary stones? Results from an in vitro PEARLS study.

BACKGROUND: The novel pulsed thulium:yttrium-aluminum-garnet (p-Tm:YAG) laser was recently introduced. Current studies present promising p-Tm:YAG ablation efficiency, although all are based on non-human stone models or with unknown stone composition. The present study aimed to evaluate p-Tm:YAG ablation efficiency for stone dust from human urinary stones of known compositions. METHODS: Calcium oxalate monohydrate (COM) and uric acid (UA) stones were subjected to lithotripsy in vitro using a p-Tm:YAG laser generator (Thulio®, Dornier MedTech GmbH, Germany). 200 J was applied at 0.1 J × 100 Hz, 0.4 J × 25 Hz or 2.0 J × 5 Hz (average 10W). Ablated stone dust mass was calculated from weight difference between pre-lithotripsy stone and post-lithotripsy fragments > 250 µm. Estimated ablated volume was calculated using prior known stone densities (COM: 2.04 mg/mm3, UA: 1.55 mg/mm3). RESULTS: Mean ablation mass efficiency was 0.04, 0.06, 0.07 mg/J (COM) and 0.04, 0.05, 0.06 mg/J (UA) for each laser setting, respectively. This translated to 0.021, 0.029, 0.034 mm3/J (COM) and 0.026, 0.030, 0.039 mm3/J (UA). Mean energy consumption was 26, 18, 17 J/mg (COM) and 32, 23, 17 J/mg (UA). This translated to 53, 37, 34 J/mm3 (COM) and 50, 36, 26 J/mm3 (UA). There were no statistically significant differences for laser settings or stone types (all p > 0.05). CONCLUSION: To our knowledge, this is the first study showing ablation efficiency of the p-Tm:YAG laser for stone dust from human urinary stones of known compositions. The p-Tm:YAG seems to ablate COM and UA equally well, with no statistically significant differences between differing laser settings.

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.

Pulsed thulium:YAG laser-ready to dust all urinary stone composition types? Results from a PEARLS analysis.

PURPOSE: To evaluate whether stone dust can be obtained from all prevailing stone composition types using the novel pulsed thulium:YAG (p-Tm:YAG), including analysis of stone particle size after lithotripsy. METHODS: Human urinary stones of 7 different compositions were subjected to in vitro lithotripsy using a p-Tm:YAG laser with 270 µm silica core fibers (Thulio®, Dornier MedTech GmbH®, Wessling, Germany). A cumulative energy of 1000 J was applied to each stone using one of three laser settings: 0.1 J × 100 Hz, 0.4 J × 25 Hz and 2.0 J × 5 Hz (average power 10 W). After lithotripsy, larger remnant fragments were separated from stone dust using a previously described method depending on the floating ability of dust particles. Fragments and dust samples were then passed through laboratory sieves to evaluate stone particle count according to a semiquantitative analysis relying on a previous definition of stone dust (i.e., stone particles ≤ 250 µm). RESULTS: The p-Tm:YAG laser was able to produce stone dust from lithotripsy up to measured smallest mesh size of 63 µm in all seven stone composition types. Notably, all dust samples from all seven stone types and with all three laser settings had high counts of particles in the size range agreeing with the definition stone dust, i.e., ≤ 250 µm. CONCLUSION: This is the first study in the literature proving the p-Tm:YAG laser capable of dusting all prevailing human urinary stone compositions, with production of dust particles ≤ 250 µm. These findings are pivotal for the broader future implementation of the p-Tm:YAG in clinical routine.

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).

Instrumental dead space and proximal working channel connector design in flexible ureteroscopy: a new concept.

Objective: The objective of this study was to evaluate a new concept in flexible ureteroscopy: instrumental dead space (IDS). For this purpose, various proximal working channel connector designs, as well as the impact of ancillary devices occupying the working channel were evaluated in currently available flexible ureteroscopes. Design and methods: IDS was defined as the volume of saline irrigation needed to inject at the proximal connector for delivery at the distal working channel tip. Because IDS is related to working channel diameter and length, proximal connector design, as well as occupation of working channel by ancillary devices, these parameters were also reviewed. Results: IDS significantly varied between flexible ureteroscope models, ranging from 1.1 ml for the Pusen bare scopes, to 2.3 ml for Olympus scopes with their 4-way connector (p < 0.001). Proximal connector designs showed a high degree of variability in the number of available Luer locks, valves, seals, angles, and rotative characteristics. The measured length of the working channel of bare scopes ranged between 739 and 854 mm and significantly correlated with measured IDS (R2 = 0.82, p < 0.001). The coupling of scopes with an alternative ancillary proximal connector and the insertion of ancillary devices into the working channel significantly reduced IDS (mean IDS reduction of 0.1 to 0.5 ml; p < 0.001). Conclusions: IDS appears as a new parameter that should be considered for future applications of flexible ureteroscopes. A low IDS seems desirable for several clinical applications. The main factors impacting IDS are working channel and proximal connector design, as well as ancillary devices inserted into the working channel. Future studies should clarify how reducing IDS may affect irrigation flow, intrarenal pressure, and direct in-scope suction, as well as evaluate the most desirable proximal connector design properties.

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.

Revised Minoan eruption volume as benchmark for large volcanic eruptions.

Despite their global societal importance, the volumes of large-scale volcanic eruptions remain poorly constrained. Here, we integrate seismic reflection and P-wave tomography datasets with computed tomography-derived sedimentological analyses to estimate the volume of the iconic Minoan eruption. Our results reveal a total dense-rock equivalent eruption volume of 34.5 ± 6.8 km³, which encompasses 21.4 ± 3.6 km³ of tephra fall deposits, 6.9 ± 2 km³ of ignimbrites, and 6.1 ± 1.2 km³ of intra-caldera deposits. 2.8 ± 1.5 km³ of the total material consists of lithics. These volume estimates are in agreement with an independent caldera collapse reconstruction (33.1 ± 1.2 km³). Our results show that the Plinian phase contributed most to the distal tephra fall, and that the pyroclastic flow volume is significantly smaller than previously assumed. This benchmark reconstruction demonstrates that complementary geophysical and sedimentological datasets are required for reliable eruption volume estimates, which are necessary for regional and global volcanic hazard assessments.

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.

Clinical performance of the Femoral Neck System within 1 year in 125 patients with acute femoral neck fractures, a prospective observational case series.

INTRODUCTION: Osteosynthesis of femoral neck fractures (FNFs) is an important treatment option, especially for younger patients. We aimed to assess the rate of early implant-related complications in FNF osteosynthesis using the Femoral Neck System (FNS). PATIENTS AND METHODS: Consecutive patients diagnosed with displaced or nondisplaced FNFs were treated with FNS in this prospective, observational, multicenter investigation. Patients were followed up for minimally 3 months and up to 12 months if radiologic bone union and no pain was not achieved beforehand. Predefined treatment-related adverse events (AEs, defined as implant failure, loss of reduction, iatrogenic fractures, deep infection, and surgical revision), radiologic bone union, and patient-reported Harris hip score (HHS) and EQ-5D-5L index score were assessed. RESULTS: One hundred and twenty-five patients were included in the study. Thirty-eight (30.4%) fractures were displaced (Garden III and IV), and 37 (29.6%) were vertical fractures (Pauwels type III). Predefined treatment-related AE rate at 3 months was 8 patients, 6.4% (95% CI, 2.8-12.2), and at 12 months, 11 patients, 8.8% (95% CI, 4.5-15.2). Cumulative incidences of bone union were 68% at 3 months, 90% at 6 months, and 98% at 12 months. The mean changes of HHS and EQ-5D-5L index score between preinjury and at 12 months were -7.5 (95% CI, [ - 21.1] to [6.2]) and - 0.03 (95% CI, [ - 0.21] to [0.15]), respectively; neither were statistically significant. CONCLUSION: The current study on osteosynthesis of FNFs with the FNS resulted in treatment-related complication rates of 6.4% (95% CI, 2.8-12.2) at 3 months and 8.8% (95% CI, 4.5-15.2) at 12 months. On average, patients returned to preinjury function and quality of life. The current study may also indicate that the conventional wisdom of treating stable FNF in patients aged between 60 and 80 years with osteosynthesis may need to be reconsidered. REGISTRATION: The study is registered with ClinicalTrials.gov (registration number: NCT02422355).

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.