OBJECTIVES:The objective of the study was to explore the distribution of gepotidacin into prostate tissue by ex vivo microdialysis (MD) after a single oral dose of gepotidacin. METHODS:We developed and validated an ex vivo MD technique to quantify unbound gepotidacin concentrations in the interstitial fluid of human prostate tissue after a single oral dose of 1500 mg. Adult male patients scheduled for radical prostatectomy received gepotidacin at different timepoints before surgery. MD probes were inserted into prostate tissue immediately after surgical removal for sampling of tissue concentrations. Plasma samples were collected in parallel. Population pharmacokinetic (popPK) modelling was used to analyse the concentration data. RESULTS:Thirty participants were recruited, of whom 24 had at least one prostate MD sample with concentrations above the limit of quantification. A popPK model was successfully developed that described plasma and prostate gepotidacin concentration well. The model-predicted geometric mean of unbound area under the concentration-time curve from zero to infinity was 15 500 h∗ng/mL (geometric coefficient of variation (GCV): 15.7%) in both prostate and plasma (prostate penetration ratio = 1). The model-predicted geometric mean of the unbound peak concentration (Cmax) of 1340 ng/mL (GCV: 38.7%) was reached after 4.25 hours (range: 3.25-12.2 hours) in prostate tissue. The model-predicted geometric mean of unbound plasma Cmax of 2090 (GCV 48.2%) ng/mL was reached after 1.75 hours (range: 0.75-8.25 hours). Model-estimated median total apparent plasma clearance and terminal apparent volume of distribution were 65.0 L/h (GCV 15.7%) and 1310 L (GCV 11.2%), respectively. CONCLUSIONS:Ex vivo MD proved feasible for quantifying gepotidacin in human prostate tissue, interstitial fluid showing exposures comparable with plasma. However, defining pharmacokinetic/pharmacodynamic targets against relevant pathogens for bacterial prostatitis remains essential for predicting drug efficacy for treatment of this disease.

Primary hyperparathyroidism (pHPT) is infrequently associated with calcium-containing kidney stones, despite hypercalciuria. Parathyroidectomy (PTX) is the only curative treatment of the metabolic disorder and is indirectly regarded as prophylaxis of recurrence of stone formation. The aim of the systematic review was to evaluate the impact of PTX on stone recurrence and to identify possible predictors of recurrent stone formation. Following PRISMA guidelines, a systematic PubMed search was conducted through April 2025. Eligible studies including adults with successfully surgically treated pHPT, documented nephrolithiasis and a follow-up of at least 12 months were analyzed. A total of 13 studies (2 prospective cohorts, 10 retrospective cohorts, 1 randomized controlled trial, RCT) comprising more than 8000 patients met the inclusion criteria. After PTX, recurrence rates in prospective studies ranged from 0–30

Abstract Ewing sarcoma is a rare, fusion-driven malignancy with poor prognosis in the metastatic setting, for which no established immunotherapeutic treatment is currently available. Fusion breakpoints are rational precision immunotherapy targets, yet clinical evidence of immunogenicity is scarce. We administered an off-the-shelf multi-peptide vaccine spanning the type 1 EWSR1–FLI1 breakpoint to a patient with high-burden metastatic Ewing sarcoma following multimodal therapy. Vaccinations were combined with GM-CSF and topical imiquimod. Longitudinal immune monitoring by in vitro peptide stimulation and intracellular cytokine staining revealed de novo polyfunctional CD4⁺ T-cell responses against all four fusion-derived peptides, first detectable by month 7 and persisting beyond two years. Treatment was well tolerated with only grade 1 local reactions. Durable disease stability was maintained for more than 26 months. These first-in-human data support the feasibility, safety, and immunogenicity of a fusion-derived peptide vaccine and warrant further evaluation of precision immunotherapy in sarcomas driven by recurrent gene fusions.

Introduction: This research investigates the influence of the medical personnel shortage on the treatment of urolithiasis by comparing the complication rates in patients with urinary stones who undergo ureterorenoscopy with laser lithotripsy before and after the emergence of this unprecedented situation. Methods: A total of 160 patients undergoing ureterorenoscopy with laser lithotripsy for urolithiasis were retrospectively evaluated, segmented into pre- and post-pandemic cohorts. Complications that occurred preoperatively (during the waiting period for operation), intraoperatively, and postoperatively were documented to compare the complication rates between the two cohorts. Results: The investigation demonstrated a significant elevation of complications during the preoperative waiting period in the post-pandemic cohort (p < 0.001), concurrent with a substantial increase in the median waiting time from 20 days to 94 days (p < 0.001). No significant differences were present in intra- and postoperative complications between the two cohorts. Conclusion: In the new era of personnel shortage, increased complication rates during the preoperative waiting time were observed, concomitant with a significant increase in the waiting times for surgery. This novel challenge of increased preoperative morbidity also led to additional resource consumption. It is imperative to adapt the therapeutic landscape of urolithiasis to the new circumstances.

INTRODUCTION:Urolithiasis is one of the most common diseases worldwide, characterized by high morbidity and significant treatment-related costs, with a rising prevalence of up to 20%. The relapse rate within the first 10 years after initial treatment is estimated to be about 60%. Given the increasing prevalence, healthcare-related costs associated with urinary tract stones in the USA are expected to reach up to US $1.24 billion annually by 2030. Current prophylactic therapy for urolithiasis recurrence includes lifestyle modifications, citrate supplementation, and pharmaceuticals. However, a high number of cases remain unresponsive to available pharmacological therapies. Though initially developed for the treatment of Diabetes mellitus, SGLT-2 inhibitors have shown promise in decreasing cardiac and renal endpoints across multiple indications. Recent registry studies have indicated that patients receiving SGLT-2 inhibitors exhibit lower rates of urolithiasis incidence, suggesting a potential reduction in recurrence rates and associated mortality. OBJECTIVES:We hypothesize that SGLT-2 inhibitors (Dapagliflozin), owing to their multiple pleiotropic effects, may offer a viable treatment option for the prophylaxis of high-risk calcium oxalate kidney stones and reduce urinary calcium oxalate output. METHODS:This study will proceed in two phases: an exploratory phase and a randomized controlled phase. In the exploratory phase, 22 participants with indications for dapagliflozin treatment will be evaluated before and after treatment initiation to ascertain the concrete effect size regarding oxalate and calcium-sparing effects. This data will inform the calculation of the study sample size (ranging from 17 to 104 participants) to include high-risk calcium oxalate kidney stone formers in a randomized controlled crossover study design. Treatment phases-one with dapagliflozin and one with placebo-will alternate with wash-out phases involving placebo. The primary outcome is the reduction of oxalate excretion in 24-hour urine samples compared to baseline values after 8 weeks of therapy. Secondary objectives include analysing effects on kidney function, the frequency of urolithiasis, and treatment tolerance. Additionally, in-depth metabolomics analyses will explore pathophysiological pathways during treatment. Investigators, patients, and research staff will be blinded to the randomization list. This study was initially registered under EudraCT (Nr:2022-000994-13) and has been transitioned to CTIS (Nr: 2024-519371-25-00) to comply with EU Regulation 536/2014, ensuring streamlined management and transparency. DISCUSSION:Dapagliflozin's pleiotropic effects may provide a novel prophylactic treatment option for urolithiasis. This study aims to evaluate potential treatment effects in a prospective RCT and elucidate potential pathophysiological pathways through in-depth metabolomics analyses. SGLT-2 inhibitors have the potential to transform the landscape of urolithiasis treatment, reduce the healthcare burden on individuals and the system, and significantly improve patient quality of life.

Background: The tumor-associated disialoganglioside GD2 is a bona fide immunotherapy target in neuroblastoma and other childhood tumors, including Ewing sarcoma and osteosarcoma. GD2-targeting antibodies proved to be effective in neuroblastoma and GD2-targeting chimeric antigen receptors (CAR)- expressing T cells as well as natural killer T cells (NKTs) are emerging. However, assessment of intra- and intertumoral heterogeneity has been complicated by ineffective immunohistochemistry as well as sampling bias in disseminated disease. Therefore, a non-invasive approach for the assessment and visualization of GD2 expression in-vivo is of upmost interest and might enable a more appropriate treatment stratification. Methods: Recently, [64Cu]Cu-NOTA-ch14.18/CHO (64Cu-GD2), a radiolabeled GD2-antibody for imaging with Positron-Emission-Tomography (PET) was developed. We here report our first clinical patients' series (n = 11) in different pediatric tumors assessed with 64Cu-GD2 PET/MRI. GD2-expression in tumors and tissue uptake in organs was evaluated by semiquantitative measurements of standardized uptake values (SUV) with PET/MRI on day 1 p.i. (n = 11) as well as on day 2 p.i. (n = 6). Results: In 8 of 9 patients with suspicious tumor lesions on PET/MRI at least one metastasis showed an increased 64Cu-GD2 uptake and a high tracer uptake (SUVmax > 10) was measured in 4 of those 8 patients. Of note, sufficient image quality with high tumor to background contrast was readily achieved on day 1. In case of 64Cu-GD2-positive lesions, an excellent tumor to background ratio (at least 6:1) was observed in bones, muscles or lungs, while lower tumor to background contrast was seen in the spleen, liver and kidneys. Furthermore, we demonstrated extensive tumor heterogeneity between patients as well as among different metastatic sites in individual patients. Dosimetry assessment revealed a whole-body dose of only 0.03 mGy/MBq (range 0.02-0.04). Conclusion: 64Cu-GD2 PET/MRI enables the non-invasive assessment of individual heterogeneity of GD2 expression, which challenges our current clinical practice of patient selection, stratification and immunotherapy application scheme for treatment with anti-GD2 directed therapies.

BACKGROUND: Suction techniques showed potential to improve outcomes of retrograde intra-renal surgery (RIRS). We assessed the 24-hour stone-free rate (SFR) and complications after RIRS using flexible and navigable suction ureteral access sheaths (FANS-UAS). METHODS: Sixteen centers prospectively contributed to data (August 2023-October 2023). Inclusion criteria: age >= 18 years, single renal stone, pre and 24-hour post-RIRS CT scan. Exclusion criteria were: ureteral stone, anomalous kidney, multiple stones. SFR was divided into: 1) grade A - no fragments; 2) grade B - fragments <= 2 mm; 3) grade C - fragments 2.1-4 mm; and 4) grade D - fragments >4 mm. A multivariable logistic regression analysis model was performed to assess factors associated with the odds of having grade A stone-free status. Data are expressed as median (interquartile range), absolute numbers and frequencies, odds ratio (OR), and 95% confidence interval (CI). RESULTS: One hundred forty-two patients with a median age of 52 years (40-61) were enrolled. 61.3% were males. Median stone volume was 1165 mm(3) (656-1936). Median operative time was 48.5 (36.25-71.75) min. Transient fever (37 degrees C-37.5 degrees C) occurred in 10 (7%) patients. No sepsis case occurred. 96.5% of patients were stone-free (Grade A+B). Grade A SFR was 52.8%. All patients were discharged within 48 hours. Bone window (OR 3.156 95% CI 1.177-9.130, P=0.027) was the only factor significantly associated with higher odds of 100% SFR, while stone volume (OR 0.999, 95% CI 0.999-1.000, P=0.007) was significantly associated with lower odds. CONCLUSIONS: Imaging and clinical evidence demonstrate excellent perioperative outcomes just 24 hours post RIRS with FANS-UAS. The technique demonstrates a good safety profile, ability for immediate high SFR, and a low rate of infective complications.

This study presents a high-dimensional immunohistochemistry approach to assess human γδ T cell subsets in their native tissue microenvironments at spatial resolution, a hitherto unmet scientific goal due to the lack of established antibodies and required technology. We report an integrated approach based on multiplexed imaging and bioinformatic analysis to identify γδ T cells, characterize their phenotypes, and analyze the composition of their microenvironment. Twenty-eight γδ T cell microenvironments were identified in tissue samples from fresh frozen human colon and colorectal cancer where interaction partners of the immune system, but also cancer cells were discovered in close proximity to γδ T cells, visualizing their potential contributions to cancer immunosurveillance. While this proof-of-principle study demonstrates the potential of this cutting-edge technology to assess γδ T cell heterogeneity and to investigate their microenvironment, future comprehensive studies are warranted to associate phenotypes and microenvironment profiles with features such as relevant clinical characteristics.

A particular challenge hampering therapeutic advancements for high-risk sarcoma patients is the broad spectrum of molecularly distinct sarcoma entities and the corresponding lack of suitable model systems to recapitulate and study these diseases. To overcome this predicament, we developed a novel genetically-controlled, yet versatile mouse modeling platform allowing delivery of different genetic lesions by electroporation (EPO) of the thigh muscle wildtype mice. This optimized sarcoma EPO-GEMM (EPO-based genetically engineered mouse model) platform allowed the generation of ten biologically distinct sarcoma entities, including Synovial Sarcoma (SS), fusion-positive and fusion-negative Rhabdomyosarcoma (RMS), Alveolar Soft Part Sarcoma (ASPS), Undifferentiated Pleomorphic Sarcoma (UPS) and Infantile Fibrosarcoma (IFS). Comprehensive molecular profiling and cross-species analyses confirmed faithful recapitulation of the human disease, including the expression of relevant immunotherapy targets. Syngeneic allografting enabled reliable preservation and scalability of Sarcoma-EPO-GEMMs for treatment trials, such as B7-H3-directed CAR-T cell therapy in an immunocompetent background. ### Competing Interest Statement Ina Oehme receives research grants from PreComb, BVD and Day One Therapeutics.

Due to the radiation exposure for the urology staff during endourology, our aim was to evaluate the trends of radiation protection in the operation room by endourologists from European centers and to estimate their annual radiation. We conducted a multicenter study involving experienced endourologists from different European centers to evaluate whether the protection and threshold doses recommended by the International Commission on Radiation Protection (ICRP) were being followed. A 36-question survey was completed on the use of fluoroscopy and radiation protection. Annual prospective data from chest, extremities, and eye dosimeters were collected during a 4-year period (2017–2020). Ten endourologists participated. Most surgeons use lead aprons and thyroid shield (9/10 and 10/10), while leaded gloves and caps are rarely used (2/10 both). Six out of ten surgeons wear leaded glasses. There is widespread use of personal chest dosimeters under the apron (9/10), and only 5/10 use a wrist or ring dosimeter and 4 use an eye dosimeter. Two endourologists use the ALARA protocol. The use of ultrasound and fluoroscopy during PCNL puncture was reported by 8 surgeons. The mean number of PCNL and URS per year was 30.9 (SD 19.9) and 147 (SD 151.9). The mean chest radiation was 1.35 mSv per year and 0.007 mSv per procedure. Mean radiation exposure per year in the eyes and extremities was 1.63 and 11.5 mSv. Endourologists did not exceed the threshold doses for radiation exposure to the chest, extremities and lens. Furthermore, the ALARA protocol manages to reduce radiation exposure.

Deciphering cellular components and the spatial interaction network of the tumor immune microenvironment (TIME) of solid tumors is pivotal for understanding biologically relevant cross-talks and, ultimately, advancing therapies. Multiplexed tissue imaging provides a powerful tool to elucidate spatial complexity in a holistic manner. We established and cross-validated a comprehensive immunophenotyping panel comprising over 121 markers for multiplexed tissue imaging using MACSima™ imaging cyclic staining (MICS) alongside an end-to-end analysis workflow. Applying this panel and workflow to primary cancer tissues, we characterized tumor heterogeneity, investigated potential therapeutical targets, conducted in-depth profiling of cell types and states, sub-phenotyped T cells within the TIME, and scrutinized cellular neighborhoods of diverse T cell subsets. Our findings highlight the advantage of spatial profiling, revealing immunosuppressive molecular signatures of tumor-associated myeloid cells interacting with neighboring exhausted, PD1high T cells in the TIME of hepatocellular carcinoma (HCC). This study establishes a robust framework for spatial exploration of TIMEs in solid tumors and underscores the potency of multiplexed tissue imaging and ultra-deep cell phenotyping in unraveling clinically relevant tumor components.

Use of suction in flexible ureteroscopy is increasing lately. The introduction of flexible and navigable suction access sheath (FANS) has shown improved stone free rate (SFR). However, its efficacy in lower pole stone (LPS) in terms of SFR and complications is yet to be studied. We collected data from 25 centers that included 394 adult patients undergoing ureteroscopy using FANS. Non contrast CT (NCCT) scan was done within first 30 days post operatively to access the SFR. Residual fragments were graded as A: 100

Abstract BACKGROUND A major challenge in the treatment of brain tumors is the limited penetration of many drugs through the blood-brain barrier (BBB). BBB characteristics include endothelial cells connected by tight junction proteins (e.g. Claudin5, ZO1, occludin) and the expression of efflux transporters (e.g. P-gp) with the physiological role to limit the accumulation of potentially toxic substances in brain tissue. Our study aims to enhance our understanding of the BBB composition across different molecular groups of ependymoma (EPN) with the goal of leveraging this knowledge to improve therapeutic strategies against these tumors. METHODS We applied a multi-omics approach integrating single-nuclear RNA sequencing and ultra-high content imaging to unravel BBB composition at both transcriptomic and proteomic levels. Patient-derived xenograft (PDX) models were utilized to explore differences in BBB penetration between tumor and healthy brain tissue following drug treatments. RESULTS Expression of tight junction and transporter proteins revealed strong dependencies specific to molecular groups, but were independent of the corresponding brain regions. Human tissue of ST-EPN-ZFTA exhibited highest expression of claudin5, while both ST-EPN-ZFTA and PF-EPN-A represented upregulation of occludin and ZO1 in comparison to healthy tissue. These findings on claudin5 and ZO1 were further confirmed in PDX models. Single-cell data analysis from patients localized the expression of relevant BBB factors to tumor-associated endothelial cells. Treatment of PDX models with drugs revealed disparities in drug penetration between EPN tumors and healthy brain regions. Notably, for most drugs BBB penetration was lower in ST-EPN-ZFTA tumors than healthy brain region. CONCLUSIONS Molecular BBB specifics may contribute to drug resistance of aggressive EPN particularly in ST-EPN-ZFTA tumors, which presented high tight junction expressions and lower drug penetration. This resource aims to improve BBB penetration prediction in EPN, to identify combination therapies targeting BBB components and to select innovative drug delivery approaches.

Tumor-associated antigens (TAAs) are potential targets for T cell-based immunotherapy approaches in cutaneous melanoma. BNT111, an investigational lipoplex-formulated mRNA-based therapeutic cancer vaccine encoding melanoma TAAs NY-ESO-1, tyrosinase, MAGE-A3, and TPTE, is undergoing clinical testing in adults. Expression of these TAAs in pediatric melanoma is unclear but is a prerequisite for feasibility of this treatment approach in children with melanoma. Our main objective was to characterize expression of those TAAs in pediatric melanomas compared to control cohorts. In this retrospective case control study, protein and transcript expression of NY-ESO-1, tyrosinase, MAGE-A3, and TPTE were analyzed in a cohort of 25 pediatric melanomas, 31 melanomas of young adults, 29 adult melanomas, and 30 benign melanocytic nevi in children using immunohistochemical staining and digital pathology (QuPath) and reverse transcription quantitative PCR. Based on IHC analysis, pediatric melanomas expressed tyrosinase (100.0%), TPTE (44.0%), MAGE-A3 (12.0%), and NY-ESO-1 (8.0%). Young adult melanomas expressed tyrosinase (96.8%), NY-ESO-1 (19.4%), MAGE-A3 (19.4%), and TPTE (3.2%). Adult melanomas expressed tyrosinase (86.2%), MAGE-A3 (75.9%), NY-ESO-1 (48.3%), and TPTE (48.3%). Childhood melanocytic nevi only expressed tyrosinase (93.3%). Expression prevalence of individual TAAs did not differ between subtypes of pediatric melanoma, and no association with prognosis was found. All four TAAs were expressed in pediatric melanoma, albeit NY-ESO-1 and MAGE-A3 to a lesser extent than in adult melanoma. These data support the possibility of investigating vaccines targeting these TAAs for the treatment of pediatric melanoma.

Urinary sepsis is the leading cause of mortality in the setting of endourological procedures for stone treatment such as URS and PCNL; renal stones themselves may be a source of infection. Aim of this study is to determine the diagnostic accuracy of stone cultures (SC) collected during URS and PCNL in predicting post-operative septic complications, compared to preoperative bladder urine culture (BUC). We performed a systematic review (SR) of literature according to the PRISMA guidelines; Literature quality was evaluated according to The Risk Of Bias In Non-randomized Studies—of Interventions (ROBINS-I) assessment tool. A univariate meta-analysis (MA) was used to estimate pooled log odds ratio of BUC and SC, respectively. Overall, 14 studies including 3646 patients met the inclusion criteria. Eight studies reported data from PCNL only; three from URS only; three from both URS and PCNL. Stone cultures showed a higher sensitivity (0.52 vs 0.32) and higher positive predictive value (0.28 vs 0.21) in predicting post-operative sepsis, compared to bladder urine cultures. The pool-weighted logarithmic odd risk (LOR) for BUC was 2.30 (95

Abstract Objectives:This study examines the impact of medical personnel scarcity on urolithiasis treatment by comparing complication rates in urinary stone patients undergoing ureterorenoscopic (URS) treatment before and after the onset of this novel circumstance. Patients and Methods:A total of 160 patients who received URS (including flexible URS) treatment for urolithiasis at the Vienna General Hospital were included. Specifically, 80 consecutive patients from the year 2018, before the scarcity of personnel, and 80 patients from 2023, following the emergence of this situation, were analyzed in two patient cohorts. Complications that occurred during the waiting period, intraoperatively, and postoperatively, were recorded. Moreover, demographic and clinical data were collected to compare the two patient cohorts. The primary endpoint was the differences in the complication rates of the two cohorts. The secondary endpoints were readmission, ureteral stent (re-)placement, stent encrustation, or length of hospital stay. Results:The study revealed a significant increase in complications during the waiting period in the 2023 cohort (p < .001), concomitant with a substantial rise in the median waitingtime from 20 days to 94 days (p < .001). No significant disparities were observed in intra- and postoperative complications. Furthermore, patients in 2023 demonstrated a higher rate of readmissions during the waiting time for surgery (16.25% vs 2.5%, p = .002) and longer length of stays (2.94 vs. 2.10 days, p < .001). Conclusion:In the new era of personnel scarcity with longer waiting time for surgery, increased complication rates during the waiting period pose a significant challenge in the treatment of urolithiasis requiring URS. There is a need for an adaptation of the treatment strategies to address this issue.

Abstract BACKGROUND Aggressive ependymoma (EPN) exhibit primary and secondary radio- and chemotherapy resistance with the poorest prognosis in the pediatric groups PF-EPN-A and ST-EPN-ZFTA. Recently, tumor cell networks formed by membrane protrusions, such as tunneling nanotubes (TNT) or tumor microtubes (TM), have been identified in other glial brain tumors. These structures facilitate intercellular hierarchical Ca2+-communication and contribute to therapy resistance. Previous data from our group suggested enhancer-regulated Ca2+-communication to be essential in EPN. This study aims to further characterize intratumoral interactions and to understand potential correlations between tumor cell connections and treatment resistance in EPN. METHODS Intercellular connections in EPN patients and model systems were characterized by scanning electron microscopy, immunofluorescence and ultra-high content imaging. Transcriptomic and proteomic data were analyzed to identify potential targetable vulnerabilities within network dynamics. Candidates were functionally validated in cell culture models applying Ca2+ live cell imaging. RESULTS Connectivity-related terms such as microtube-based movement or microtube bundle formation showed increased expression in EPN transcriptome data compared to healthy controls. EPN networks were found to be build of TM- and TNT-like structures with a higher abundance of TNT-like structures in PF-EPN-A compared to ST-EPN-ZFTA. All networks showed strong Nestin-positivity in cells, mouse models and human tumor tissue of ST-EPN-ZFTA and PF-EPN-A. Thrombospondin-1, a matricellular protein enhancing TMs in glioma cells, was strongly enriched in ST-EPN-ZFTA patients. The gap junction channel connexin 43, connecting glioma cells, was highly upregulated in PF-EPN-A. Active electrochemical communication was observed between ST-EPN-ZFTA cells performing Ca2+ imaging. Moreover, inhibition of T-type Ca2+ channels impaired intercellular signaling, leading to network perturbation in vitro. CONCLUSIONS Our study revealed the importance of gap junction-coupled networks for communication of aggressive EPN cells. Targeted disconnection of the EPN-specific network as demonstrated for Ca2+ channel inhibition suggests a new avenue for therapeutic strategies in EPN to overcome resistance.

Over the past three decades, there has been increasing interest in miniaturized percutaneous nephrolithotomy (mPCNL) techniques featuring smaller tracts as they offer potential solutions to mitigate complications associated with standard PCNL (sPCNL). However, despite this growing acceptance and recognition of its benefits, unresolved controversies and acknowledged limitations continue to impede widespread adoption due to a lack of consensus on optimal perioperative management strategies and procedural tips and tricks. In response to these challenges, an international panel comprising experts from the International Alliance of Urolithiasis (IAU) took on the task of compiling an expert consensus document on mPCNL procedures aimed at providing urologists with a comprehensive clinical framework for practice. This endeavor involved conducting a systematic literature review to identify research gaps (RGs), which formed the foundation for developing a structured questionnaire survey. Subsequently, a two-round modified Delphi survey was implemented, culminating in a group meeting to generate final evidence-based comments. All 64 experts completed the second-round survey, resulting in a response rate of 100.0%. Fifty-eight key questions were raised focusing on mPCNLs within 4 main domains, including general information (13 questions), preoperative work-up (13 questions), procedural tips and tricks (19 questions), and postoperative evaluation and follow-up (13 questions). Additionally, 9 questions evaluated the experts' experience with PCNLs. Consensus was reached on 30 questions after the second-round survey, while professional statements for the remaining 28 key questions were provided after discussion in an online panel meeting. mPCNL, characterized by a tract smaller than 18 Fr and an innovative lithotripsy technique, has firmly established itself as a viable and effective approach for managing upper urinary tract stones in both adults and pediatrics. It offers several advantages over sPCNL including reduced bleeding, fewer requirements for nephrostomy tubes, decreased pain, and shorter hospital stays. The series of detailed techniques presented here serve as a comprehensive guide for urologists, aiming to improve their procedural understanding and optimize patient outcomes.

Current treatment outcome of patients with glioblastoma (GBM) remains poor. Following standard therapy, recurrence is universal with limited survival. Tumors from 173 GBM patients are analysed for somatic mutations to generate a personalized peptide vaccine targeting tumor-specific neoantigens. All patients were treated within the scope of an individual healing attempt. Among all vaccinated patients, including 70 treated prior to progression (primary) and 103 treated after progression (recurrent), the median overall survival from first diagnosis is 31.9 months (95% CI: 25.0-36.5). Adverse events are infrequent and are predominantly grade 1 or 2. A vaccine-induced immune response to at least one of the vaccinated peptides is detected in blood samples of 87 of 97 (90%) monitored patients. Vaccine-specific T-cell responses are durable in most patients. Significantly prolonged survival is observed for patients with multiple vaccine-induced T-cell responses (53 months) compared to those with no/low induced responses (27 months; P = 0.03). Altogether, our results highlight that the application of personalized neoantigen-targeting peptide vaccine is feasible and represents a promising potential treatment option for GBM patients.