Current Knowledge and Opinions of Medical Trainees Regarding PSA Screening.

After 2008 and 2012 USPSTF recommendations against PSA screening, studies revealed a decline in screening rates and trend towards more advanced disease at presentation. After revision of this recommendation in 2017, PSA screening guidelines remain inconsistent and controversy still exists about its clinical utility. We seek to better understand the knowledge of medical trainees regarding this fundamental controversy and gain better insight into what they are being taught regarding this topic. Participants were medical students (n = 66) and residents (n = 60) from a single institution. REDCap software was used for informed consent, survey distribution, and data collection. Variables measured included PSA clinical knowledge, awareness of the PSA guideline changes, and attitudes, confidence, and viewpoints on use of PSA screening in clinical practice. More than 60% of medical trainees reported little or no knowledge of PSA screening guidelines. Although residents reported more knowledge than medical students, actual assessed knowledge of PSA screening did not differ between groups. Trainees reported receiving education primarily from other healthcare professionals and didactics, with some self-learning online. Though confidence was low overall, residents were more confident than medical students in discussing PSA screening with patients. The majority of respondents wanted more information about PSA testing, with medical students particularly interested in diagnosis/detection, treatment, and survival. Overall, opinions towards PSA testing as an aid were generally positive. Better education about the current PSA screening guidelines for medical trainees is imperative, particularly given that shared decision-making is of great importance when counseling patients on cancer screening.

Frailty and geriatric assessment in urologic oncology.

PURPOSE OF REVIEW: As the population ages, urologic oncologists are caring for older and more vulnerable patients that must withstand complex surgical treatments. Our healthcare environment emphasizes surgical quality, reductions in length of hospital stay, reduced readmission rates, and high patient satisfaction. So those who manage urologic malignancies must be able to optimize their patients. Understanding the concept of frailty, how to diagnose it in a timely and reliable manner, appreciate its perioperative impact, and consider interventions to reduce its effects may improve surgical outcomes. RECENT FINDINGS: There has been a recent swell of early research regarding frailty in urologic oncology and its related perioperative effects. Increasing degrees of frailty are associated with greater morbidity and mortality, and more adverse discharge disposition after surgical procedures. Clinicians are, thus, recognizing the value of geriatric assessment in their practice and exploring ways to integrate it using a team-based approach. Universal geriatric recommendations are now available in specific urologic populations to guide these efforts. Importantly, formal geriatric assessment outperforms physician discretion or the 'eyeball' test. SUMMARY: The current review offers a comprehensive study of the impact of frailty in urologic oncology, methods for its assessment, and active interventions to reduce it.

Human anti-nucleolin recombinant immunoagent for cancer therapy.

Nucleolin (NCL) is a nucleocytoplasmic protein involved in many biological processes, such as ribosomal assembly, rRNA processing, and mRNA stabilization. NCL also regulates the biogenesis of specific microRNAs (miRNAs) involved in tumor development and aggressiveness. Interestingly, NCL is expressed on the surface of actively proliferating cancer cells, but not on their normal counterparts. Therefore, NCL is an attractive target for antineoplastic treatments. Taking advantage of phage-display technology, we engineered a fully human single-chain fragment variable, named 4LB5. This immunoagent binds NCL on the cell surface, it is translocated into the cytoplasm of target cells, and it abrogates the biogenesis of NCL-dependent miRNAs. Binding of 4LB5 to NCL on the cell surface of a variety of breast cancer and hepatocellular carcinoma cell lines, but not to normal-like MCF-10a breast cells, dramatically reduces cancer cell viability and proliferation. Finally, in orthotopic breast cancer mouse models, 4LB5 administration results in a significant reduction of the tumor volume without evident side effects. In summary, here we describe, to our knowledge, the first anti-NCL single-chain fragment variable displaying antineoplastic activity against established solid tumors, which could represent the prototype of novel immune-based NCL-targeting drugs with clinical potential as diagnostic and therapeutic tools in a wide variety of human cancers.

The Application of Next-Generation Sequencing in Preoperative Evaluation for Urologic Stone Surgery.

Introduction: Next-generation sequencing (NGS) is a new molecular technique for identifying microorganisms. Treating bacteriuria in patients undergoing stone removal procedures is important for preventing postoperative urinary tract infection (UTI). The objective of this study is to assess the usefulness of preoperative urine NGS testing by comparing NGS with standard urine culture in predicting postoperative UTI after ureteroscopic lithotripsy (URSL) and percutaneous nephrolithotomy (PCNL). Materials and Methods: This prospective study was conducted from February 16, 2022, to January 11, 2024. Sixty subjects who underwent URSL or PCNL were included. Preoperative voided urine samples were collected for urine culture and tested by MicroGenDX for urine polymerase chain reaction (PCR) and urine NGS. Stone specimens obtained intraoperatively were also sent for stone culture and MicrogenDx. Patients were monitored for 4 weeks post-operation for recording clinical outcomes related to infections and complications. Results: Twenty-six (43.3%) male and 34 (56.7%) female participants were included. Twenty-six (43.3%) patients underwent PCNL (15 standard PCNL and 11 mini PCNL), and 34 (56.7%) underwent URSL. Standard urine culture identified positive results in 26 cases (43.3%), PCR for 17 cases (28.3%), and NGS for 31 cases (51.7%). The overall postoperative UTI rate was 6 (10%). Standard urine culture demonstrated a sensitivity of 50%, specificity of 57.4%, and accuracy of 56.7%. Positive predictive value (PPV) was notably poor at 11.5%. Urine NGS showed a higher sensitivity of 83.3%, specificity of 53.7%, accuracy of 55%, and PPV of 16.7%. Conclusion: Urine NGS significantly improves the sensitivity of detecting microorganisms in preoperative urine compared with standard urine culture. Despite its high sensitivity and capability to identify nonculturable bacteria, using NGS alongside standard urine culture is recommended. This parallel approach harnesses the strengths of both methods. Integrating NGS into standard practice could elevate the quality of care, especially for patients at high risk of UTIs, such as those undergoing invasive stone removal procedures.

A career exploration didactic and simulation-based session increases student knowledge in and exposure to urology.

INTRODUCTION: Though urology attracts well-qualified applicants, students are not typically provided exposure to this smaller specialty until later in their medical education. While simulation-based training continues to supplement medical education, there is a lack of programming to teach specialty-specific procedural skills to medical students and those outside the specialty. We report a half-day simulation and didactic-based approach to increase exposure to urology to interested second-year medical students. METHODS: A half-day didactic- and simulation-based session was offered to second-year medical students (N=57). After a didactic-based overview of the specialty performed by urology providers and a surgical educator, the students participated in small-group simulations, including hands-on simulations. The students completed a post-curriculum survey measuring knowledge gains and soliciting feedback on the session. RESULTS: Students were 57.1% Caucasian, 66.7% female, with a mean age of 24.2 years; 80% stated they were potentially interested in pursuing a surgical specialty such as urology prior to the start of the session. Students reported pre- to post-curriculum gains in knowledge (mean=37%) about a career in urology and basic urologic procedures (p<0.001). Participants were also likely to recommend the curriculum to their peers (p<0.001). CONCLUSIONS: Given that exposure to urology in medical school is usually limited and offered later in training, a half-day didactic- and simulation-based experience for second-year students provides an early introduction and experience within the specialty and its common bedside procedures.

Integrative Transcriptomic Analysis Reveals Distinctive Molecular Traits and Novel Subtypes of Collecting Duct Carcinoma.

Collecting duct carcinoma (CDC) is a rare and highly aggressive kidney cancer subtype with poor prognosis and no standard treatments. To date, only a few studies have examined the transcriptomic portrait of CDC. Through integration of multiple datasets, we compared CDC to normal tissue, upper-tract urothelial carcinomas, and other renal cancers, including clear cell, papillary, and chromophobe histologies. Association between CDC gene expression signatures and in vitro drug sensitivity data was evaluated using the Cancer Therapeutic Response Portal, Genomics of Drug Sensitivity in Cancer datasets, and connectivity map. We identified a CDC-specific gene signature that predicted in vitro sensitivity to different targeted agents and was associated to worse outcome in clear cell renal cell carcinoma. We showed that CDC are transcriptionally related to the principal cells of the collecting ducts providing evidence that this tumor originates from this normal kidney cell type. Finally, we proved that CDC is a molecularly heterogeneous disease composed of at least two subtypes distinguished by cell signaling, metabolic and immune-related alterations. Our findings elucidate the molecular features of CDC providing novel biological and clinical insights. The identification of distinct CDC subtypes and their transcriptomic traits provides the rationale for patient stratification and alternative therapeutic approaches.

NCL Inhibition Exerts Antineoplastic Effects against Prostate Cancer Cells by Modulating Oncogenic MicroRNAs.

Prostate cancer (PCa) is the most frequently diagnosed cancer in men and second most common cause of cancer-related deaths in the United States. Androgen deprivation therapy (ADT) is only temporarily effective for advanced-stage PCa, as the disease inevitably progresses to castration-resistant prostate cancer (CRPC). The protein nucleolin (NCL) is overexpressed in several types of human tumors where it is also mislocalized to the cell surface. We previously reported the identification of a single-chain fragment variable (scFv) immuno-agent that is able to bind NCL on the surface of breast cancer cells and inhibit proliferation both in vitro and in vivo. In the present study, we evaluated whether NCL could be a valid therapeutic target for PCa, utilizing DU145, PC3 (CRPC), and LNCaP (androgen-sensitive) cell lines. First, we interrogated the publicly available databases and noted that higher NCL mRNA levels are associated with higher Gleason Scores as well as with recurrent and metastatic tumors. Then, using our anti-NCL scFv, we demonstrated that NCL is expressed on the surface of all three tested cell lines and that NCL inhibition results in reduced proliferation and migration. We also measured the inhibitory effect of NCL targeting on the biogenesis of oncogenic microRNAs such as miR-21, -221 and -222, which was cell context dependent. Taken together, our data provide evidence that NCL targeting inhibits the key hallmarks of malignancy in PCa cells and may provide a novel therapeutic option for patients with advanced-stage PCa.

Genetic ablation of interacting with Spt6 (Iws1) causes early embryonic lethality.

IWS1 is an RNA-polymerase II (RNAPII)-associated transcription elongation factor whose biological functions are poorly characterized. To shed some light on the function of this protein at the organismal level, we performed a systematic tissue analysis of its expression and generated Iws1-deficient mice. A thorough immunohistochemical characterization shows that IWS1 protein is present in the nucleus of all cells in most of the examined tissues, with few notable exceptions. We also report that ablation of Iws1 consistently causes lethality at the pre-implantation stage with high expression of the gene in fertilized oocytes. In summary, we are providing evidence that Iws1 is expressed in all adult organs and it is an essential gene for mouse embryonic development.

Ran Binding Protein 9 (RanBP9) is a novel mediator of cellular DNA damage response in lung cancer cells.

Ran Binding Protein 9 (RanBP9, also known as RanBPM) is an evolutionary conserved scaffold protein present both in the nucleus and the cytoplasm of cells whose biological functions remain elusive. We show that active ATM phosphorylates RanBP9 on at least two different residues (S181 and S603). In response to IR, RanBP9 rapidly accumulates into the nucleus of lung cancer cells, but this nuclear accumulation is prevented by ATM inhibition. RanBP9 stable silencing in three different lung cancer cell lines significantly affects the DNA Damage Response (DDR), resulting in delayed activation of key components of the cellular response to IR such as ATM itself, Chk2, γH2AX, and p53. Accordingly, abrogation of RanBP9 expression reduces homologous recombination-dependent DNA repair efficiency, causing an abnormal activation of IR-induced senescence and apoptosis. In summary, here we report that RanBP9 is a novel mediator of the cellular DDR, whose accumulation into the nucleus upon IR is dependent on ATM kinase activity. RanBP9 absence hampers the molecular mechanisms leading to efficient repair of damaged DNA, resulting in enhanced sensitivity to genotoxic stress. These findings suggest that targeting RanBP9 might enhance lung cancer cell sensitivity to genotoxic anti-neoplastic treatment.

Quaking and miR-155 interactions in inflammation and leukemogenesis.

Quaking (QKI) is a tumor-suppressor gene encoding a conserved RNA-binding protein, whose expression is downregulated in several solid tumors. Here we report that QKI plays an important role in the immune response and suppression of leukemogenesis. We show that the expression of Qki is reduced in lipopolysaccharide (LPS)-challenged macrophages, suggesting that Qki is a key regulator of LPS signaling pathway. Furthermore, LPS-induced downregulation of Qki expression is miR-155-dependent. Qki overexpression impairs LPS-induced phosphorylation of JNK and particularly p38 MAPKs, in addition to increasing the production of anti-inflammatory cytokine IL-10. In contrast, Qki ablation decreases Fas expression and the rate of Caspase3/7 activity, while increasing the levels of IL-1α, IL-1ß and IL-6, and p38 phosphorylation. Similarly, the p38 pathway is also a target of QKI activity in chronic lymphocytic leukemia (CLL)-derived MEC2 cells. Finally, B-CLL patients show lower levels of QKI expression compared with B cells from healthy donor, and Qki is similarily downregulated with the progression of leukemia in Eµ-miR-155 transgenic mice. Altogether, these data implicate QKI in the pathophysiology of inflammation and oncogenesis where miR-155 is involved.