ß2-microglobulin triggers NLRP3 inflammasome activation in tumor-associated macrophages to promote multiple myeloma progression.

As substantial constituents of the multiple myeloma (MM) microenvironment, pro-inflammatory macrophages have emerged as key promoters of disease progression, bone destruction, and immune impairment. We identify beta-2-microglobulin (ß2m) as a driver in initiating inflammation in myeloma-associated macrophages (MAMs). Lysosomal accumulation of phagocytosed ß2m promotes ß2m amyloid aggregation in MAMs, resulting in lysosomal rupture and ultimately production of active interleukin-1ß (IL-1ß) and IL-18. This process depends on activation of the NLRP3 inflammasome after ß2m accumulation, as macrophages from NLRP3-deficient mice lack efficient ß2m-induced IL-1ß production. Moreover, depletion or silencing of ß2m in MM cells abrogates inflammasome activation in a murine MM model. Finally, we demonstrate that disruption of NLRP3 or IL-18 diminishes tumor growth and osteolytic bone destruction normally promoted by ß2m-induced inflammasome signaling. Our results provide mechanistic evidence for ß2m's role as an NLRP3 inflammasome activator during MM pathogenesis. Moreover, inhibition of NLRP3 represents a potential therapeutic approach in MM.

Lower urinary tract signs and symptoms in patients with COVID-19.

BACKGROUND: The type of pneumonia that is caused by the new coronavirus (SARS-CoV-2) has spread across the world in a pandemic. It is not clear if COVID-19 patients have any lower urinary tract signs or symptoms. METHODS: The effect of COVID-19 on lower urinary tract function was studied in a prospective multi-centre, observational study including 238 patients who were admitted with symptoms caused by COVID-19 to the university hospital of Aachen in Germany and Tabriz in Iran. RESULTS: None of the patients reported to have any lower urinary tract symptoms. SARS-CoV-2 was found in the urine of 19% of the tested patients. The mortality rate in COVID-19 infected patients with microscopic haematuria together with white blood cells in their urine, was significantly increased from 48 to 61% in the Tabriz cohort (p-value = 0.03) and from 30 to 35% in the Aachen cohort (p-value =0.045). Furthermore, in the group of patients with SARS-CoV-2 urine PCR, the mortality rate rose from 30 to 58%. (p-value =0.039). CONCLUSION: Patients admitted with COVID-19 did not report to have any lower urinary tract symptoms, even those patient who had a positive Urine SARS-CoV-2 PCR. In addition, hematuria, WBC in urine as well as SARS- CoV-2 presence in urine, were found to be strong negative prognostic factors in admitted COVID-19 patients.

A noninvasive diagnostic approach to retrospective donor HLA typing in kidney transplant patients using urine.

Antibody-mediated rejection (AMR) is a major obstacle to long-term kidney transplantation. AMR is mostly caused by donor specific HLA antibodies, which can arise before or any time after transplantation. Incomplete donor HLA typing and unavailability of donor DNA regularly preclude the assessment of donor-specificity of circulating anti-HLA antibodies. In our centre, this problem arises in approximately 20% of all post-transplant HLA-antibody assessments. We demonstrate that this diagnostic challenge can be resolved by establishing donor renal tubular cell cultures from recipient´s urine as a source of high-quality donor DNA. DNA was then verified for genetic origin and purity by fluorescence in situ hybridization and short tandem repeat analysis. Two representative cases highlight the diagnostic value of this approach which is corroborated by analysis of ten additional patients. The latter were randomly sampled from routine clinical care patients with available donor DNA as controls. In all 12 cases, we were able to perform full HLA typing of the respective donors confirmed by cross-comparison to results from the stored 10 donor DNAs. We propose that this noninvasive diagnostic approach for HLA typing in kidney transplant patients is valuable to determine donor specificity of HLA antibodies, which is important in clinical assessment of suspected AMR.

Sustained PU.1 levels balance cell-cycle regulators to prevent exhaustion of adult hematopoietic stem cells.

To provide a lifelong supply of blood cells, hematopoietic stem cells (HSCs) need to carefully balance both self-renewing cell divisions and quiescence. Although several regulators that control this mechanism have been identified, we demonstrate that the transcription factor PU.1 acts upstream of these regulators. So far, attempts to uncover PU.1's role in HSC biology have failed because of the technical limitations of complete loss-of-function models. With the use of hypomorphic mice with decreased PU.1 levels specifically in phenotypic HSCs, we found reduced HSC long-term repopulation potential that could be rescued completely by restoring PU.1 levels. PU.1 prevented excessive HSC division and exhaustion by controlling the transcription of multiple cell-cycle regulators. Levels of PU.1 were sustained through autoregulatory PU.1 binding to an upstream enhancer that formed an active looped chromosome architecture in HSCs. These results establish that PU.1 mediates chromosome looping and functions as a master regulator of HSC proliferation.

ITIH5 and ECRG4 DNA Methylation Biomarker Test (EI-BLA) for Urine-Based Non-Invasive Detection of Bladder Cancer.

Bladder cancer is one of the more common malignancies in humans and the most expensive tumor for treating in the Unites States (US) and Europe due to the need for lifelong surveillance. Non-invasive tests approved by the FDA have not been widely adopted in routine diagnosis so far. Therefore, we aimed to characterize the two putative tumor suppressor genes ECRG4 and ITIH5 as novel urinary DNA methylation biomarkers that are suitable for non-invasive detection of bladder cancer. While assessing the analytical performance, a spiking experiment was performed by determining the limit of RT112 tumor cell detection (range: 100-10,000 cells) in the urine of healthy donors in dependency of the processing protocols of the RWTH cBMB. Clinically, urine sediments of 474 patients were analyzed by using quantitative methylation-specific PCR (qMSP) and Methylation Sensitive Restriction Enzyme (MSRE) qPCR techniques. Overall, ECRG4-ITIH5 showed a sensitivity of 64% to 70% with a specificity ranging between 80% and 92%, i.e., discriminating healthy, benign lesions, and/or inflammatory diseases from bladder tumors. When comparing single biomarkers, ECRG4 achieved a sensitivity of 73%, which was increased by combination with the known biomarker candidate NID2 up to 76% at a specificity of 97%. Hence, ITIH5 and, in particular, ECRG4 might be promising candidates for further optimizing current bladder cancer biomarker panels and platforms.

Leiomyoma arising from the right seminal duct/seminal vesicle-Report of a rare case and review of the literature.

We present a case of a patient with a large, symptomatic abdominal tumour, which finally could be classified as a leiomyoma arising from the right seminal duct/seminal vesicle. In computed tomography (CT) scan, it appeared as a 7.5 × 6.5 cm solid, supravesical mass. A cystoscopy as well as bilateral retrograde studies was normal, a transrectal ultrasound-guided biopsy and an ultrasound-guided transabdominal biopsy of the mass were inconclusive. Subsequently, we performed a tumour extirpation through a lower midline laparotomy. Histological examination showed a leiomyoma arising from the right seminal duct or seminal vesicle. In this article, we discuss clinical presentation, findings on imaging and management of this rare benign tumour and review the relevant literature where only 13 similar cases could be identified.

Twelve-Year Follow-Up of Navigated Computer-Assisted Versus Conventional Total Knee Arthroplasty: A Prospective Randomized Comparative Trial.

BACKGROUND: Navigated computer-assisted total knee arthroplasty (TKA) was introduced to expedite long-term survival based on improved postoperative implantation accuracy. However, long-term outcome data after 10 years or more are rare, even available meta-analyses show controversial study results. METHODS: In a prospective randomized trial, 100 conventional TKAs (group CONV) were compared with 100 computer-assisted TKAs (group NAV) after a mean follow-up of 12 years postoperatively. A long-leg weight-bearing X-ray was performed for measuring mechanical axis of the limb, lateral distal femoral angle, and medial proximal tibial angle. Tibial slope, patella alpha angle, and radiolucent lines were also observed. Clinical investigation included evaluation of 4 different scores: Insall Knee Score, Western Ontario and MacMaster University Index score, Hospital for Special Surgery Knee Score, and visual analog scale. RESULTS: Based on a follow-up rate of at least 75%, no difference in TKA survival was found 12 years postoperatively: 91.5% in group CONV vs 98.2% in group NAV (P = .181). Since 5-year follow-up, no additional TKA revision had been performed in both groups. Group CONV showed a nonsignificant higher inaccuracy of neutral lower limb axis (1.8° ± 1.4°) compared to group NAV (1.6° ± 1.7°, P = .700). All X-ray assessments were not significant different within both study groups (P ≥ .068). Clinical examination showed no differences in evaluations (P ≥ .204). All collected outcome score results were similar (P ≥ .222). CONCLUSION: Twelve years postoperatively, no differences were found in terms of long-term survival, implantation accuracy, clinical outcome or score results.

Diagnostic and Prognostic Implications of FGFR3high/Ki67high Papillary Bladder Cancers.

Prognostic/therapeutic stratification of papillary urothelial cancers is solely based upon histology, despite activated FGFR3-signaling was found to be associated with low grade tumors and favorable outcome. However, there are FGFR3-overexpressing tumors showing high proliferation-a paradox of coexisting favorable and adverse features. Therefore, our study aimed to decipher the relevance of FGFR3-overexpression/proliferation for histopathological grading and risk stratification. N = 142 (n = 82 pTa, n = 42 pT1, n = 18 pT2-4) morphologically G1⁻G3 tumors were analyzed for immunohistochemical expression of FGFR3 and Ki67. Mutation analysis of FGFR3 and TP53 and FISH for FGFR3 amplification and rearrangement was performed. SPSS 23.0 was used for statistical analysis. Overall FGFR3high/Ki67high status (n = 58) resulted in a reduced ∆mean progression-free survival (PFS) (p < 0.01) of 63.92 months, and shorter progression-free survival (p < 0.01; mean PFS: 55.89 months) in pTa tumors (n = 50). FGFR3mut/TP53mut double mutations led to a reduced ∆mean PFS (p < 0.01) of 80.30 months in all tumors, and FGFR3mut/TP53mut pTa tumors presented a dramatically reduced PFS (p < 0.001; mean PFS: 5.00 months). Our results identified FGFR3high/Ki67high papillary pTa tumors as a subgroup with poor prognosis and encourage histological grading as high grade tumors. Tumor grading should possibly be augmented by immunohistochemical stainings and suitable clinical surveillance by endoscopy should be performed.

Characteristics of donor-specific anti-HLA antibodies and outcome in renal transplant patients treated with a standardized induction regimen.

Background: Pre-transplant donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) have been associated with antibody-mediated rejection (AMR) and early kidney allograft loss. Uncertainties remain regarding the general applicability of these findings and the optimal induction therapy in DSA-positive patients. Methods: Pre-transplant sera from 174 patients receiving a crossmatch-negative kidney transplant were retrospectively analysed for DSA using Luminex technology. DSA with mean-fluorescence intensity (MFI) values above 500 were considered positive. All recipients received basiliximab induction and tacrolimus-based maintenance immunosuppression. DSA were monitored post-transplantation in patients with pre-transplant DSA. Antibody results were correlated with the incidence of rejection and graft loss. Results: In total, 61/174 patients had pre-transplant DSA. We found a strong correlation between the presence of DSA against class I and II HLA and DSA MFI greater than 10 000. Both DSA patterns independently predicted an increased risk of early AMR (odds ratio 4.24 and 4.75, respectively, P < 0.05). The risk for AMR in patients with intermediate MFI (3000-10 000) gradually increased with increasing MFI but group sizes were too small to allow for final conclusions. The risk for AMR was comparable to nonsensitized patients in patients with only class I or II HLA-DSA or MFI below 3000. 5-year allograft survival was lowest in patients with simultaneous presence of class I and II HLA-DSA and MFI above 10 000 (45%) but was comparable between patients with only HLA class I or II or no DSA (90.0, 90.0 and 88.1%, respectively). AMR was the only independent predictor of graft loss. Undetectable DSA 14 days post-transplant predicted excellent long-term outcome. Conclusion: . The favourable outcome in the majority of DSA-positive patients despite non-depleting antibody induction and the poor outcome in patients with class I and II HLA-DSA and high DSA strength call for a differentiated therapeutic approach in this patient population.

Fusion rate and clinical outcome in anterior lumbar interbody fusion with beta-tricalcium phosphate and bone marrow aspirate as a bone graft substitute. A prospective clinical study in fifty patients.

PURPOSE: Bone graft substitutes have been successfully used in posterolateral lumbar fusion, anterior cervical fusion and animal studies. This study has been conducted to assess the safety and efficacy of ß-tricalcium phosphate (ß-TCP) in instrumented anterior lumbar interbody fusion (ALIF) procedure. METHODS: In a prospective clinical study, ALIF cages were prefilled with ß-TCP and additionally fixated with posterior pedicle screw. Computed tomography (CT) and X-rays were performed one year after surgery. Fusion was assessed and functional status was evaluated before and one year after surgery. RESULTS: X-ray evaluation showed a definite fusion in 85.48 % of treated levels. CT assessment showed anterior and posterior intersegemental bone bridging in 77.78 % of treated levels. CONCLUSIONS: The X-ray fusion rate presented is comparable with those published for ALIF procedures with bone graft. Fusion rates ß-TCP are similar to autologous bone. ALIF with ß-TCP and additional posterior fixation is a safe and effective procedure.

Comparison of two- and three-dimensional measurement of the Cobb angle in scoliosis.

PURPOSE: The Cobb angle as an objective measure is used to determine the progression of deformity, and is the basis in the planning of conservative and surgical treatment. However, studies have shown that the Cobb angle has two limitations: an inter- and intraobserver variability of the measurement is approximately 3-5 degrees, and high variability regarding the definition of the end vertebra. Scoliosis is a three-dimensional (3D) pathology, and 3D pathologies cannot be completely assessed by two-dimensional (2D) methods, like 2D radiography. The objective of this study was to determine the intraobserver and interobserver reliability of end vertebra definition and Cobb angle measurement using X-rays and 3D computer tomography (CT) reconstructions in scoliotic spines. METHODS: To assess interoberver variation the Cobb angle and the end vertebra were assessed by five observers in 55 patients using X-rays and 3D CT reconstructions. Definition of end vertebra and measurement of the Cobb angle was repeated two times with a three-week interval. Intraclass correlation coefficients (ICC) were used to determine the interobserver and intraobserver reliabilities. 95% prediction limits were provided for measurement errors. RESULTS: Intraclass correlation coefficient (ICC) showed excellent reliability for both methods. The measured Cobb angle was on average 9.2 degrees larger in the 3D CT group (72.8°, range 30-144) than on 2D radiography (63.6°, range 24-152). CONCLUSIONS: In scoliosis treatment it is very essential to determine the curve magnitude, which is larger in a 3D measurement compared to 2D radiography.

The Runx-PU.1 pathway preserves normal and AML/ETO9a leukemic stem cells.

Runx transcription factors contribute to hematopoiesis and are frequently implicated in hematologic malignancies. All three Runx isoforms are expressed at the earliest stages of hematopoiesis; however, their function in hematopoietic stem cells (HSCs) is not fully elucidated. Here, we show that Runx factors are essential in HSCs by driving the expression of the hematopoietic transcription factor PU.1. Mechanistically, by using a knockin mouse model in which all three Runx binding sites in the -14kb enhancer of PU.1 are disrupted, we observed failure to form chromosomal interactions between the PU.1 enhancer and its proximal promoter. Consequently, decreased PU.1 levels resulted in diminished long-term HSC function through HSC exhaustion, which could be rescued by reintroducing a PU.1 transgene. Similarly, in a mouse model of AML/ETO9a leukemia, disrupting the Runx binding sites resulted in decreased PU.1 levels. Leukemia onset was delayed, and limiting dilution transplantation experiments demonstrated functional loss of leukemia-initiating cells. This is surprising, because low PU.1 levels have been considered a hallmark of AML/ETO leukemia, as indicated in mouse models and as shown here in samples from leukemic patients. Our data demonstrate that Runx-dependent PU.1 chromatin interaction and transcription of PU.1 are essential for both normal and leukemia stem cells.

NOTCH2 and FLT3 gene mis-splicings are common events in patients with acute myeloid leukemia (AML): new potential targets in AML.

Our previous studies revealed an increase in alternative splicing of multiple RNAs in cells from patients with acute myeloid leukemia (AML) compared with CD34(+) bone marrow cells from normal donors. Aberrantly spliced genes included a number of oncogenes, tumor suppressor genes, and genes involved in regulation of apoptosis, cell cycle, and cell differentiation. Among the most commonly mis-spliced genes (>70% of AML patients) were 2, NOTCH2 and FLT3, that encode myeloid cell surface proteins. The splice variants of NOTCH2 and FLT3 resulted from complete or partial exon skipping and utilization of cryptic splice sites. Longitudinal analyses suggested that NOTCH2 and FLT3 aberrant splicing correlated with disease status. Correlation analyses between splice variants of these genes and clinical features of patients showed an association between NOTCH2-Va splice variant and overall survival of patients. Our results suggest that NOTCH2 and FLT3 mis-splicing is a common characteristic of AML and has the potential to generate transcripts encoding proteins with altered function. Thus, splice variants of these genes might provide disease markers and targets for novel therapeutics.

High-Risk Non-Muscle-Invasive Bladder Cancer-Therapy Options During Intravesical BCG Shortage.

Bladder cancer is the second commonest urinary tract malignancy with 70-80 % being non-muscle invasive (NMIBC) at diagnosis. Patients with high-risk NMIBC (T1/Tis, with high grade/G3, or CIS) represent a challenging group as they are at greater risk of recurrence and progression. Intravesical Bacilli Calmette-Guerin (BCG) is commonly used as first line therapy in this patient group but there is a current worldwide shortage. BCG has been shown to reduce recurrence in high-risk NMIBC and is more effective that other intravesical agents including mitomycin C, epirubicin, interferon-alpha and gemcitabine. Primary cystectomy offers a high change of cure in this cohort (80-90 %) and is a more radical treatment option which patients need to be counselled carefully about. Bladder thermotherapy and electromotive drug administration with mitomycin C are alternative therapies with promising short-term results although long-term follow-up data are lacking.

Current Trends in Urolithiasis Treatment in Various European Health Systems.

OBJECTIVE: In spite of readily available evidence-based guidelines on urolithiasis treatment, practical applications of treatments vary from country to country, or even within countries. The choice of treatment depends not only on the evidence, but often on general non-medical decision factors such as infrastructure, expertise, trends, patient demands, industry drive and reimbursement levels. In turn, many of these factors are interdependent and a result of the individual National Health System. METHOD: In an attempt to get a crude picture of trends and practices in stone treatment across Europe, a group of well-renowned international experts in the field were asked to reply to a set of standard questions relating to stone treatments, health systems and adherence to guidelines (level of evidence D = expert opinion). RESULTS: The above-mentioned interdependencies showed a varying picture in different countries. Overall, there is a trend away from lithotripsy and toward ureterorenoscopy. However, the choice of treatment is largely dependent on the affordability of infrastructure. Urologists may make choices based on the national reimbursement system, too. CONCLUSION: Without claiming to represent a scientifically sound study, this survey represents an interesting insight into a representative cross-section of European urological current practices and trends in urolithiasis treatment.

C/EBPα is required for development of dendritic cell progenitors.

Dendritic cells (DCs) are master regulators of the immune system, but molecular regulation of early DC differentiation has been poorly understood. Here, we report that the transcription factor C/EBPα coordinates the development of progenitor cells required for production of multiple categories of DCs. C/EBPα was needed for differentiation from stem/progenitor cells to common DC progenitors (CDPs), but not for transition of CDP to mature DCs. C/EBPα deletion in mature DCs did not affect their numbers or function, suggesting that this transcription factor is not needed for maintenance of DCs in lymphoid tissues. ChIP-seq and microarrays were used to identify candidate genes regulated by C/EBPα and required for DC formation. Genes previously shown to be critical for DC formation were bound by C/EBPα, and their expression was decreased in the earliest hematopoietic compartments in the absence of C/EBPα. These data indicate that C/EBPα is important for the earliest stages of steady-state DC differentiation.

Revision of Articular Surface Replacement (ASR) Total Hip Arthroplasty: Correlation of Perioperative Data and Early Post-Revision Outcome Results.

The articular surface replacement (ASR) total hip arthroplasty (THA) showed accelerated failure rates due to adverse-reaction to metal debris (ARMD). Literature correlating preoperative with intraoperative revision findings respectively post-revision outcome results are rare. 30 of 99 available ASR THA were revised due to ARMD. Mean post-revision follow-up term was 2.3 years. In part, preoperative data did not correlate with intraoperative revision findings. ARMD was even found in asymptomatic patients with non-elevated ion levels. Postoperative pain and metal ions decreased significantly (P ≤ 0.016). Cobalt decreased faster than chrome. Patients with intraoperative pseudotumors, osteolysis or bilateral THA did not have higher pre- or postoperative ion values (P ≥ 0.053). Females showed higher postoperative chrome levels (P=0.031). One major post-revision complication (femoral nerve palsy) and one re-revision (late onset infection) occurred.

Monitoring of hematopoietic chimerism by real-time quantitative PCR of micro insertions/deletions in samples with low DNA quantities.

BACKGROUND: Sensitive and accurate methods to detect hematopoietic chimerism after hematopoietic stem cell transplantation (HSCT) are essential to evaluate engraftment and to monitor response to therapeutic procedures such as donor lymphocyte infusion. Continuous long-term follow up, however, requires large amounts of pre-HSCT samples limiting the application of many widely used techniques for sensitive chimerism monitoring. METHODS: DNAs from 42 normal healthy donors and 16 HSCT donor/recipient pairs were employed to validate the use of allele-specific insertion/deletion (indel) quantitative real-time polymerase chain reaction (qPCR) to quantify chimerism in samples with low amounts of DNA. Consequently, indel-qPCR analyses of samples from 16 HSCT patients were compared to short-tandem repeat (STR) specific PCR analyses. RESULTS: Typing with reduced amounts of input DNA (15 vs. 60 ng) allowed for the reliable distinction of positive (mean threshold cycle (ct) 28.05) and negative (ct >36) signals. The high informativity of primer/probe sets, with 12 out of 19 markers exceeding 20% informativity, was confirmed in our cohort (n = 74). Importantly, a fourfold reduction of input DNA compared to published protocols did not alter PCR efficiencies and allowed for a more sensitive detection of chimerism in 7 of 16 HSCT patients compared to results obtained by STR-PCR. CONCLUSIONS: Our data suggest that indel-qPCR is a more sensitive technique for the detection of hematopoietic chimerism compared to STR-PCR and works efficiently for samples with low amounts of DNA.

A model to assess the feasibility of shifting reaction equilibrium by acetone removal in the transamination of ketones using 2-propylamine.

Acetone removal by evaporation has been proposed as a simple and cheap way to shift the equilibrium in the biocatalytic asymmetric synthesis of optically pure chiral amines, when 2-propylamine is used as the amine donor. However, dependent on the system properties, this may or may not be a suitable strategy. To avoid excessive laboratory work a model was used to assess the process feasibility. The results from the current study show that a simple model of the acetone removal dependence on temperature and sparging gas flowrate can be developed and fits the experimental data well. The model for acetone removal was then coupled to a simple model for biocatalyst kinetics and also for loss of substrate ketone by evaporation. The three models were used to simulate the effects of varying the critical process parameters and reaction equilibrium constants (K eq) as well as different substrate ketone volatilities (Henry's constant). The simulations were used to estimate the substrate losses and also the maximum yield that could be expected. The approach was seen to give a clear indication for which target amines the acetone evaporation strategy would be feasible and for which amines it would not. The study also shows the value of a modeling approach in conceptual process design prior to entering a biocatalyst screening or engineering program to assess the feasibility of a particular process strategy for a given target product.

The Post-Ureteroscopic Lesion Scale (PULS): a multicenter video-based evaluation of inter-rater reliability.

PURPOSE: The Post-Ureteroscopic Lesion Scale (PULS) offers a simple grading system for the description of ureteral lesions after ureteroscopy. In this article, we present the results of a video-based multicenter evaluation of the inter-rater reliability of clinically important PULS grades 0-3. METHODS: Video sequences at the end of ureteroscopy (final passage) were recorded for 100 consecutive patients at a single institution and assessed by experienced urologists (n = 20) and senior residents (n = 17) at 19 international centers. The cohort included only patients with lesions grades 0-3 (with grades 2 and 3 subsumed as 2 + since distinction is defined by an extravasation of contrast medium in fluoroscopy). The gradings were evaluated for inter-rater reliability and in terms of simplicity, validity, comprehensibility, reproducibility, and usefulness. RESULTS: Overall, inter-rater reliability was high (Kendall's W = 0.69, p < 0.001) and was comparable between specialists (Kendall's W = 0.69, p < 0.001) and residents (Kendall's W = 0.71, p < 0.001). The matched ratings showed grade 0 in 43.0 % of patients and grades 1 or 2 + in 44.0 and 13.0 % of patients, respectively. Results of the questionnaires indicated a high degree of acceptance, with an overall rating of 1.76 (1.64-1.93 for different items, scale 1-6). CONCLUSIONS: Inter-rater reliability of the endoscopically assessable PULS was high among urologists with different levels of experience in different countries worldwide. The validated PULS system may be used for standardized reporting of ureteral lesions/injuries after ureteroscopy. In addition, PULS will enable more selective standardization of indications for postoperative DJ stenting based on the randomized controlled trials.