Citations

aims: We assessed the diagnostic accuracy of the SVEAT score in predicting 30-day major adverse cardiac events (MACE) in comparison with the well-established HEART and TIMI scores. background: Acute chest pain (ACP) is a common symptom in emergency departments. Various risk stratification tools have been developed to assess patients presenting with ACP. The Simple Vascular Event Assessment Tool (SVEAT) is the most recent scoring system introduced, based on five variables: Symptoms of chest pain, history of Vascular disease, ECG, Age, and Troponin-I. objective: We assessed the diagnostic accuracy of the SVEAT score in predicting 30-day major adverse cardiac events (MACE) in comparison with the well-established HEART and TIMI scores. method: Following PRISMA guidelines, a systematic literature search was conducted across five databases until June 22, 2024. Four studies comprising 1,520 patients were included in this meta-analysis. The predictive accuracy of the SVEAT, HEART, and TIMI scores for 30-day MACE was assessed by the area under the receiver operating characteristic curve (AUC). Heterogeneity was evaluated using the I² statistic, with values over 75% indicating significant heterogeneity. Indirect comparisons among the scores were performed using the Z-test. result: Pooled AUC for the SVEAT score was 0.92 (95% CI: 0.86-0.98), indicating superior predictive accuracy compared to the HEART (AUC: 0.86, 95% CI: 0.81-0.92) and TIMI (AUC: 0.82, 95% CI: 0.69-0.96) scores. However, significant heterogeneity (I² = 90.6%) was observed across studies, potentially due to variations in patient demographics, clinical settings, and outcome definitions. Despite the higher AUC, indirect Z-test comparisons revealed no statistically significant differences between the scoring systems. conclusion: SVEAT score demonstrates potential as an accurate tool for predicting 30-day MACE in patients with ACP. other: N/A

Abstract Background Measurement of cardiac troponin (cTn) using high-sensitivity assays is recommended for the diagnosis of myocardial infarction. We determined sex-specific and uniform 99th percentile upper reference limits (URLs) using the new Elecsys® Troponin T high-sensitivity Gen 6 assay in a global, healthy reference range cohort. Methods Lithium-heparin plasma and serum samples were prospectively collected from apparently healthy individuals aged ≥20 years across 34 global sites in the United States, Europe, China, and Japan. cTnT was measured using the Troponin T high-sensitivity Gen 6 assay on the Cobas® e 801 analyzer. Exclusion criteria were defined according to the 2022 IFCC guidance. Uniform and sex-specific 99th percentile URLs and nonparametric 95% CIs were determined in plasma and serum separately and combined. Results The final study population comprised 4147 participants (52.5% female) with a median (25th–75th percentiles) age of 48.0 (33.0–59.0) years; 45.8%, 47.9%, 5.2%, and 1.1% were White, Asian, Black, and other/unknown, respectively. For sample matrices combined (n = 8294), 81.0% and 99.2% of cTnT values were above the limit of detection in females and males, respectively. Sex-specific 99th percentile URLs (95% CI) were 18 (16–23) ng/L for females and 32 (28–35) ng/L for males; the uniform 99th percentile URL was 27 (24–31) ng/L. URLs were comparable in plasma and serum samples. Conclusions This study determined sex-specific and uniform 99th percentile URLs for the Troponin T high-sensitivity Gen 6 assay that were comparable irrespective of the matrix used in a large, global, healthy reference population.

Abstract Introduction There is wide variation in male fertility preservation practices. While physician preference accounts for some of this diversity, practice patterns often reflect multiple extrinsic factors including patient demographics, equipment availability, laboratory protocols, and state law. Objective We sought to characterize national trends in sperm retrieval and storage across reproductive urology practices in the United States. Methods An anonymous 34-item survey characterizing provider demographics, practice settings, fertility preservation procedures, andrology laboratory practices, and cryopreservation expenses was designed. Practicing reproductive urologists were identified using information available through professional societies. Our survey was constructed using the Qualtrics platform and distributed electronically between October 2024 and May 2025. Results 39 responses were received by urologists practicing across 21 states (response rate: 21%, n=189). A majority (74%, n=29) of survey responders practiced at academic medical centers, with others practicing at non-academic hospitals (8%, n=3) and private practices (13%, n=5). The most common indications for fertility preservation reported included oncologic care (42%), gamete storage for planned ART (31%), transgender care (18%), pre-vasectomy sperm banking (10%), and pre-deployment banking for military personnel (5%). Nearly all providers performed microsurgical sperm retrievals (97%, n=38, Figure) and oncologic testicular sperm extractions (85%, n=33) when indicated. More than half of providers offered conventional testicular sperm extractions (72%, n=28), microsurgical epididymal sperm aspirations (59%, n=23), testicular sperm aspirations (56%, n=22), penile vibratory stimulation (54%, n=21), or percutaneous epididymal sperm aspirations (52%, n=20). Fewer providers offered post-mortem sperm retrieval (49%, n=19), pre-pubertal testicular tissue cryopreservation (36%, n=14), or electroejaculation (31%, n=12). Most respondents (62%, n=24) had access to an on-site andrology laboratory. Semen analyses were evaluated using manual (53%, n=20), computer-assisted (11%, n=4), or combinatorial methods (26%, n=10). Though many (37%, n=14) providers were uncertain about institutional costs for semen specimen processing, a plurality of respondents (40%, n=15) reported fees ranging from $100-500 with the remainder (23%, n=9) reporting fees exceeding $500. Respondents most frequently reported semen storage fees ranging between $100-300 per year (39%, n=15), while approximately a third (31%, n=12) estimated these costs to range between $300-600 per year. However, 18% (n=7) of respondents reported higher costs for specimen storage and 13% (n=5) were uncertain about the expense of this service. Conclusions This multi-institutional, geographically diverse survey reveals significant variation in reproductive urology practice patterns and cost associated with semen analyses and storage. Future studies will explore differences in practice patterns to better understand the factors influencing this variation and their effect on male reproductive healthcare. In the absence of society guidelines, reproductive urologists must collaborate, share best practices, and maintain price transparency to ensure sperm retrieval remains accessible and affordable. Disclosure No

Abstract Introduction While microdeletions in the azoospermia factor (AZF) regions of the Y chromosome are a well-recognized cause of genetic male infertility, reproductive outcomes and broader health profiles among affected men remain poorly characterized. Objective We explore the distribution of AZF deletion subtypes and evaluate comorbidities and fertility management patterns in this unique population. Methods We performed a multi-institutional retrospective cohort study of men diagnosed with AZF deletions following evaluation by a reproductive urologist and genetic testing. The primary exposure variable was the AZF subtype (AZFa, AZFb, AZFc, or multilocus [e.g., AZFabc]).Clinical data were extracted to assess the presence of comorbidities, including hypertension, diabetes mellitus, hyperlipidemia, liver disease, and cardiac disease. Descriptive statistics were used to characterize the distribution of AZF subtypes, comorbidity profile, and outcomes of sperm retrieval procedures within our cohort. Results Among 40 men with confirmed AZF microdeletions across three academic centers, four patients with SRY translocations were excluded. Of the remaining 36, AZFc was the most common subtype (75%), followed by multilocus (16.6%), AZFa (5.5%), and AZFb (2.7%). The median age was 32.8 years (IQR: 29.2–33.6) and median BMI was 28.6 kg/m2 (IQR: 25.6–32.8). Comorbid conditions were identified in 8% of the cohort, with hyperlipidemia (13.9%), hypertension (11%), and diabetes (11%) most commonly reported. Sperm retrieval was attempted in 31% (n=11) of patients, exclusively among those with AZFc (n=10) andAZFb (n=1) deletions. Microscopic testicular sperm extraction (mTESE) was the predominant technique (91%). Sperm was successfully retrieved in 46% of these cases, all within the AZFc subgroup. Conclusions This study advances limited literature on AZF microdeletions by characterizing systemic health profiles and post-diagnosis infertility management. Our results support a broad phenotype associated with genetic causes of male infertility. In this cohort of men with YCMD, AZFc was the most prevalent subtype. Compared to national estimates for similarly aged men, our findings suggest that men with YCMD may have a distinct comorbidity profile compared to the general population, with an elevated prevalence of metabolic disease. Our findings reinforce male infertility as a heterogeneous condition that may serve as an early marker for broader metabolic disease. In addition, nearly all patients who underwent sperm retrieval were within the AZFc group. Fertility management trends favored mTESE, with moderate success rates in sperm retrieval, particularly among AZFc patients. Our results highlight provider preferences in surgical fertility management in patients withYCMD. Our findings underscore the need for a holistic approach to men with YCMD, addressing both surgical fertility management and systemic health risks. Clear patient counseling on sperm retrieval success rates and early identification of comorbidities may redefine outcomes for this unique population. Our results support a broad phenotype associated with genetic causes of male infertility. Disclosure No

Abstract Introduction Fertility preservation is an essential component to cancer survivorship. One third of male survivors experience infertility following gonadotoxic treatments, and expeditious preservation prior to therapy is recommended by oncology guidelines. However, this can be challenging given time constraints, lab expertise, and financial considerations. Objective We describe national practice patterns and identify barriers and facilitators regarding inpatient male fertility preservation. Methods An anonymous 34-item Qualtrics survey was sent to reproductive Urologists in the United States. Email addresses were obtained from public membership databases. Respondents were queried across several domains, including provider demographics, specific inpatient cryopreservation scenarios, and fertility preservation procedures. Results Thirty-nine (21%, n=39/189) responses were received. The majority of respondents were fellowship-trained reproductive urologists 89.7% (35). The majority (97.4%) of respondents offer microdissection testicular sperm extraction (mTESE) for fertility preservation, and many offer conventional TESE (71.8%), traditional ejaculated sperm cryopreservation (71.8%), or microsurgical epididymal sperm aspiration (59%). Only 30.8% of respondents offer electroejaculation. Respondents rate non-urology provider awareness of male cancer fertility preservation options at 5.05/10 on a Likert scale. Many (65%) respondents provide formal materials or education to nonurology providers to address this deficit. On average, respondents reported 2.6 inpatient oncofertility preservation consults per month (range 0-25, median=1). Most (60%) of respondents reported that <25% of these patients ultimately complete inpatient preservation. Financial burdens (97%), logistical hurdles (97%), limited awareness (97%), and concern for delay of oncologic care (92%) were identified as the most common barriers for patients precluding fertility preservation. In addition, 85% of respondents also listed difficulty coordinating with other specialists as a barrier. On free-text queries, respondents identified facilitators of fertility preservation as automatically triggered consults, use of an urgent cryopreservation pager, formal fertility preservation pathway within the order set, and utilization of an inpatient coordinator as facilitators that aid in achieving timely fertility preservation prior to gonadotoxic therapies. Conclusions Despite all reproductive urologists offering cryopreservation services and education regarding the urgency and priority of inpatient fertility preservation, less than a quarter of patients complete this process during hospitalization prior to initiation of treatment. This remains the consequence of numerous patient, provider, and facility level barriers, even in systems with robust referral processes. Inpatient fertility preservation remains an underutilized and often missed opportunity. Multidisciplinary interventions are needed to address ongoing barriers. Disclosure No

Abstract Introduction Chronic scrotal content pain (CSCP), defined as three or more months of scrotal pain interfering with daily life, affects approximately 100,000 men annually in the United States. Historically, the absence of standardized guidelines led to wide variability in diagnosis and treatment. At the time of our study design and data collection, no formal guidance existed for CSCP. In April 2025, after the study’s completion, the American Urological Association (AUA) published its first clinical guidelines for CSCP. Our findings now offer important context regarding real-world practice patterns before guideline publication. Objective To characterize diagnostic and treatment strategies for CSCP among U.S. reproductive urologists. Methods An anonymous 25-question Qualtrics survey was distributed to U.S.-based reproductive urologists. The survey assessed physician demographics, diagnostic evaluations, conservative and surgical treatment strategies, and perceived patient outcomes. Descriptive statistics were calculated, and comparisons were performed using Mann-Whitney U, chi-square, or Fisher’s exact tests, as appropriate. Results Of 183 invited physicians, 41 (22.4%) completed the survey in full. All respondents were fellowship-trained, practicing urologists, with most board-certified (82.9%). Respondents were nearly evenly split between ≤5 years (48.8%) and >5 years (51.2%) in practice. Among ten conservative treatment options, reassurance (41.5%) and NSAIDs (31.7%) were the most frequently selected first-line treatments, with median ranks of 2.5 and 2, respectively (Figure 1). Opioid medications were the least favored (median rank: 10), with 56.1% ranking them last. Pelvic floor physical therapy (PFPT) had a favorable median rank of 3 and was ranked higher by those with ≤5 years in practice compared to those in practice >5 years (median: 3 vs. 4, p = 0.019). GABA analogues and tricyclic antidepressants were assigned median ranks of 6 and 7.5, respectively. The most commonly performed surgical procedure for CSCP was microsurgical denervation of the spermatic cord (MDSC, 95.1%), followed by varicocelectomy (92.7%), vasectomy reversal (78.0%), epididymectomy (73.2%), and orchiectomy (51.2%). For post-vasectomy pain syndrome, MDSC was preferred by 63.4%, followed by vasectomy reversal (22.0%) and epididymectomy (9.8%). Among those performing vasectomy reversals, 80% of patients paid out-of-pocket (IQR: 50.0–93.5%). Respondents perceived surgical management as more effective than conservative treatment, with median complete symptom resolution rates of 70% (IQR: 50–80%) versus 25% (IQR: 10–40%) (p < 0.001). Only 7.3% reported using validated tools like the Chronic Orchialgia Symptom Index (COSI) to evaluate patient outcomes. Conclusions Our study offers a contemporary snapshot of CSCP management among reproductive urologists, revealing substantial variability in practice. Surgery was consistently perceived as more effective than conservative approaches. These findings underscore areas of alignment and divergence with the newly released AUA guidelines and support the need for future comparative trials and implementation studies to guide standardized, evidence-based care. Disclosure No

Abstract Introduction Male-factor infertility contributes to a substantial portion of infertility cases. Genetic factors are believed to play an important role, with Y chromosome microdeletions commonly identified among men with azoospermia. Due to the relatively high prevalence of these deletions, genetic testing for Y chromosome microdeletions has become a routine component of the diagnostic workup for infertile men. While deletions in the AZF (Azoospermia Factor) region are known to impair spermatogenesis, the hormonal profile in this population remains poorly characterized. Hormonal evaluation plays a key role in guiding treatment decisions, including the use of empirical medical therapy (EMT). However, there is limited data on hormonal profiles and EMT usage in men with AZF deletions. Objective We aimed to characterize preoperative hormonal profiles and evaluate the use and outcomes of EMT in men with AZF microdeletions undergoing surgical sperm retrieval. Methods We conducted a multi-institutional retrospective cohort study of men with genetically confirmed AZF micro-deletions, including AZFa, AZFb, AZFc, and combined deletions. Data were collected on preoperative serum gonadotropin levels (follicle-stimulating hormone [FSH] and luteinizing hormone [LH]), total testosterone (TT), and semen analysis parameters. Additionally, we evaluated patterns of empirical medical therapy (EMT) prescriptions and outcomes of surgical sperm retrieval. Results 40 men with confirmed Y-chromosomal micro-deletions across three academic centers was identified. Patients with SRY translocations (n=4) were excluded from the study. The final cohort included 27 patients with AZFc deletions (75%), 2 with AZFa (6%), 1 with AZFb (3%), and 6 with multilocus deletions (17%). FSH (reference: >7.6 mIU/mL) was elevated in 23 patients (64%), with a median of 19.6 IU/L (IQR: 14.4–25.8). LH (reference: >9 mIU/mL) was elevated in 8 patients (22%), with a median of 14.9 IU/L (IQR: 13.7–20.1). Overall median TT was 243.5 (7.7-379.7). TT was below the lower limit of normal (<300 ng/dL) in 13 patients (36%), with a median of 184 ng/dL (IQR: 133–233). Most patients were azoospermic on semen analysis (86%, n=31/36). Of the seven men treated with EMT, the majority (6/7, 86%) received clomiphene citrate. While there were differences in initial levels of TT, FSH, and LH for those treated with EMT compared to those without EMT, these were not statistically significant (Table 1). Among the 13 patients who underwent surgical sperm retrieval, 6 (46%) had successful outcomes; however, only one had received EMT. Conclusions Men with AZF deletions exhibit varying degrees of hormonal imbalance and rates of empirical medical therapy (EMT) use. Despite EMT, sperm retrieval outcomes were poor, with only 1 out of 7 EMT-treated patients achieving successful sperm retrieval. While hormonal differences were observed between those who received EMT and those who did not, these differences did not reach statistical significance. This is likely due to the limited sample size inherent to this rare patient population. Our findings underscore the variability in hormonal profiles and the unclear efficacy of EMT in promoting spermatogenesis in men with AZF deletions, highlighting the need for further research to inform standardized management strategies. Disclosure No

Abstract Introduction Oncologic testicular sperm extraction (oncoTESE) remains a poorly defined concept that is a heterogeneous and understudied fertility preservation option for cancer patients with male gonads. Given variation in practice patterns, reproductive insurance coverage, and provider availability, there is significant diversity among the accepted indications, desired evaluations, and surgical practices afforded to patients facing a cancer diagnosis. Objective This study aimed to characterize and help further define oncoTESE practice patterns across the United States. Methods A 34-item, anonymized survey assessed provider demographics and oncoTESE practice patterns, including indications, contraindications, workflows, and institutional barriers surrounding OncoTESE procedures. A survey was created and electronically distributed to reproductive urologists across the United States using email addresses obtained via society membership websites. Results Thirty-eight urologists (20%, 38/189) from 21 states responded to the survey. Most (95%, 36/38) were fellowship-trained reproductive urologists, and nearly all (87%, 33/38) reported offering oncoTESE to indicated patients. The most cited indications for oncoTESE were azoospermia (78%, 28/36), anejaculation (72%, 26/36), and severe oligozoospermia or cryptozoospermia on ejaculated specimen (53%, 19/36). Less commonly reported indications included prepubertal or peripubertal status (33%, 12/36) and elevated sperm DNA fragmentation (19%, 7/36). Relative contraindications included inability to consent (86%, 31/36), clinical instability (83%, 30/36), thrombocytopenia (61%, 22/36), and a history of remote chemotherapy (58%, 21/36). When asked how many semen analyses are obtained to confirm azoospermia before proceeding to oncoTESE in patients able to ejaculate, the majority reported two analyses (67%, 24/36), while 28% (10/36) reported one. There was stronger consensus that oncoTESE includes sperm retrieval during back-table orchiectomy (94%, 34/36) and ipsilateral microTESE during partial orchiectomy (86%, 31/36). Greater variability was noted regarding contralateral microTESE at the time of orchiectomy (64%, 23/36), procedures for non-genitourinary malignancies (61%, 22/36), and delayed procedures performed years after diagnosis (42%, 15/36). (Figure 1) Estimated patient costs for oncoTESE were most commonly reported as $2,000–$5,000 (39%, 14/36), followed by $500–$2,000 (22%, 8/36), $5,000–$10,000 (19%, 7/36), and over $10,000 (3%, 1/36); 14% (5/36) were unsure. On a 10-point Likert scale, the most significant barriers to performing oncoTESE were logistical challenges (mean 6.6, median 8), followed by patient cost (mean 5.4, median 5.5) and patient illness (mean 5.3, median 5.0). Conclusions This multi-institutional survey found strong agreement among reproductive urologists on core procedural elements, but substantial variation on oncoTESE definition, patient selection criteria, pre-procedural evaluation, and fertility preservation management. Similar institutional barriers across centers highlight opportunities to improve accessibility and standardize oncoTESE practices. Disclosure No

Abstract Uterine leiomyosarcoma (ULMS) is an orphan disease that frequently recurs and metastasizes, with patients undergoing multiple lines of chemotherapy due to lack of effective therapeutic targets. To address this gap, we used single-cell RNA sequencing and spatial transcriptomic analysis to comprehensively profile ULMS. We uncovered multiple states of tumor cells, including tumor cells with mesenchyme-like features, ischemic tumor cells defined by a MYC program, inflammatory tumor cells with active interferon signaling, and stem cell-like hormone receptor-positive cells. The inferred spatial correlates of these tumor cell states demonstrated unique localization patterns. By correlating these signatures to bulk RNA sequencing data, we demonstrate the relevance of these findings to clinical outcomes. Finally, using the single-cell integration and drug response prediction algorithm (scIDUC), we propose drug predictions that may target specific tumor states. Our findings suggest new avenues for further exploration of individualized and multifaceted therapeutic strategies to treat ULMS.

In the phase III placebo-controlled DeFi trial (ClinicalTrials.gov identifier: NCT03785964 ) primary analysis, nirogacestat showed significant improvement versus placebo in progression-free survival (PFS), objective response rate (ORR), and patient-reported outcomes (PRO) in adult patients with progressing desmoid tumors (DT; median [range] exposure: 20.6 [0.3-33.6] months). Here, long-term nirogacestat efficacy and safety were evaluated in patients randomly assigned to nirogacestat and followed through the final data cutoff date of December 19, 2024. End points included PFS and ORR per RECIST v1.1, PRO, and safety. The median (range) duration of exposure was 33.6 (0.3-61.8) months. Median PFS was not reached. The ORR with up to 4 years of nirogacestat treatment was 45.7% (32 of 70), with three additional partial and three additional complete responses since the primary analysis. Further target tumor size reduction occurred in most patients. Benefits in PROs were sustained while on treatment. Frequently reported treatment-emergent adverse events (TEAEs) decreased in incidence and severity over time. Since the primary analysis, four patients discontinued nirogacestat because of TEAEs between years 2 and 4. In conclusion, long-term continuous nirogacestat treatment was associated with further tumor size reductions, durable objective responses, sustained PRO benefits, and a manageable safety profile consistent with the primary analysis.