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Ultrasonography (Seoul, Korea) May 2024To provide more accurate and definitive conclusions regarding the clinical and technical complications associated with the transperineal (TP) and transrectal (TR)...
PURPOSE
To provide more accurate and definitive conclusions regarding the clinical and technical complications associated with the transperineal (TP) and transrectal (TR) approaches, a comprehensive review of observational studies and randomized controlled trials was conducted. This systematic review covered all eligible studies to facilitate a thorough comparison of complications linked to the two fiducial marker insertion methods, TP and TR.
METHODS
A comprehensive search of the literature was conducted, encompassing databases such as PubMed, Embase, and the Cochrane Library, up to July 7, 2023. The relative risk and 95% confidence interval were utilized to evaluate the diagnosis and complication rates.
RESULTS
The final selection for the methodological quality analysis included 13 observational studies that utilized TP and TR gold fiducial insertion approaches. The meta-analysis revealed significantly lower risks of urinary tract infections (UTI) and rectal bleeding with the TP approach.
CONCLUSION
The use of both TP and TR techniques for placing gold seed fiducial markers has proven to be an effective, safe, and well-tolerated method for image-guided radiation therapy in prostate cancer patients. A significant benefit of the TP technique is its ability to avoid rectal puncture, thereby reducing the risk of UTIs. Although the incidence of UTIs and rectal bleeding associated with the TR method is relatively low, these complications can disrupt patient wellbeing and potentially cause delays in treatment.
PubMed: 38898635
DOI: 10.14366/usg.23229 -
Canadian Urological Association Journal... Jun 2024Generative artificial intelligence (AI) has proven to be a powerful tool with increasing applications in clinical care and medical education. CHATGPT has performed...
INTRODUCTION
Generative artificial intelligence (AI) has proven to be a powerful tool with increasing applications in clinical care and medical education. CHATGPT has performed adequately on many specialty certification and knowledge assessment exams. The objective of this study was to assess the performance of CHATGPT 4 on a multiple-choice exam meant to simulate the Canadian urology board exam.
METHODS
Graduating urology residents representing all Canadian training programs gather yearly for a mock exam that simulates their upcoming board-certifying exam. The exam consists of written multiple-choice questions (MCQs) and an oral objective structured clinical examination (OSCE). The 2022 exam was taken by 29 graduating residents and was administered to CHATGPT 4.
RESULTS
CHATGPT 4 scored 46% on the MCQ exam, whereas the mean and median scores of graduating urology residents were 62.6%, and 62.7%, respectively. This would place CHATGPT's score 1.8 standard deviations from the median. The percentile rank of CHATGPT would be in the sixth percentile. CHATGPT scores on different topics of the exam were as follows: oncology 35%, andrology/benign prostatic hyperplasia 62%, physiology/anatomy 67%, incontinence/female urology 23%, infections 71%, urolithiasis 57%, and trauma/reconstruction 17%, with ChatGPT 4's oncology performance being significantly below that of postgraduate year 5 residents.
CONCLUSIONS
CHATGPT 4 underperforms on an MCQ exam meant to simulate the Canadian board exam. Ongoing assessments of the capability of generative AI is needed as these models evolve and are trained on additional urology content.
PubMed: 38896484
DOI: 10.5489/cuaj.8800 -
Diagnostics (Basel, Switzerland) Jun 2024A remarkable paradigm shift has emerged regarding the preferred prostate biopsy approach, favoring the transperineal (TP) over the transrectal (TR) approach due to the...
Transition from Transrectal to Transperineal MRI-Fusion Prostate Biopsy Does Not Comprise Detection Rates of Clinically Significant Prostate Cancer at a Tertiary Care Center.
BACKGROUND
A remarkable paradigm shift has emerged regarding the preferred prostate biopsy approach, favoring the transperineal (TP) over the transrectal (TR) approach due to the reduced risk of severe urinary tract infections. However, its impact on the detection of clinically significant prostate cancer (csPCa) remains unclear.
MATERIALS AND METHODS
We relied on a prospectively maintained tertiary care database to identify patients who underwent either TP or TR prostate biopsy between 01/2014 and 12/2023. Of those, only patients with suspicious magnetic resonance imaging (MRI) PIRADS lesions (Likert-scale: 3,4,5) received MRI-targeted and systematic biopsies. Detection rates of csPCa (International Society of Urological Pathology [ISUP] ≥ 2) were compared between biopsy approach (TP vs. TR) according to index lesion. Subsequently, uni- and multivariable logistic regression models were applied to investigate the predictive status of the biopsy approach within each subcohort.
RESULTS
Of 2063 patients, 1118 (54%) underwent combined MRI-guided and systematic prostate biopsy and were included in the final cohort. Of those, 127 (11%) and 991 (89%) underwent TP vs. TR. CsPCa rates, regardless of differences in patients' demographics and distribution of index PIRDAS lesions, did not differ statistically significantly and were 51 vs. 52%, respectively ( = 0.8). CsPCa detection rates for PIRDAS-3, PIRADS-4 and PIRADS-5 did not differ and were 24 vs. 23%, 48 vs. 51% and 72 vs. 76% for PIRADS-3, PIRADS-4 and PIRADS-5 subgroups for TP vs. TR, respectively (all ≥ 0.9) Conclusions: The current results support the available data indicating that TP biopsy approach is comparable to transrectal biopsy approach regarding csPCa detection rates.
PubMed: 38893710
DOI: 10.3390/diagnostics14111184 -
International Journal of Molecular... May 2024Recently, a compound derived from recent scientific advances named has emerged as the focus of this research, the aim of which is to explore its potential impact on...
Recently, a compound derived from recent scientific advances named has emerged as the focus of this research, the aim of which is to explore its potential impact on solid tumor cell lines. Using a combination of bioinformatics and biological assays, this study conducted an in-depth investigation of the effects of . The results of this study have substantial implications for cancer research and treatment. has shown remarkable efficacy in inhibiting the growth of several cancer cell lines, including those representing prostate carcinoma (PC3) and cervical carcinoma (HeLa). The high sensitivity of these cells, indicated by low IC values, underscores its potential as a promising chemotherapeutic agent. In addition, has revealed the ability to induce cell cycle arrest, particularly in the G2/M phase, a phenomenon with critical implications for tumor initiation and growth. By interfering with DNA replication in cancer cells, has shown the capacity to trigger cell death, offering a new avenue for cancer treatment. In addition, computational analyses have identified key genes affected by treatment, suggesting potential therapeutic targets. These genes are involved in critical biological processes, including cell cycle regulation, DNA replication and microtubule dynamics, all of which are central to cancer development and progression. In conclusion, this study highlights the different mechanisms of that inhibit cancer cell growth and alter the cell cycle. These promising results suggest the potential for more effective and less toxic anticancer therapies. Further in vivo validation and exploration of combination therapies are critical to improve cancer treatment outcomes.
Topics: Humans; Microtubules; Antineoplastic Agents; Cell Line, Tumor; Acrylonitrile; Cell Proliferation; Neoplasms; HeLa Cells; Apoptosis; Triazoles; Cell Cycle Checkpoints; Tubulin Modulators; PC-3 Cells
PubMed: 38891892
DOI: 10.3390/ijms25115704 -
Methods in Enzymology 2024Peptide drugs are a promising alternative to classical small molecule therapeutics with diverse applications, ranging from antibiotic resistant infection to prostate...
Peptide drugs are a promising alternative to classical small molecule therapeutics with diverse applications, ranging from antibiotic resistant infection to prostate cancer. Oxytocin (OT) is a highly evolutionarily conserved peptide neurohormone and has been of interest for pharmaceutical use since 1909. Despite their increased safety profile relative to most small molecule drugs, peptides are poor candidates based on the pharmacokinetic (PK) properties from their peptide nature. Broad application of OT as a drug has been limited by these same PK issues. Several strategies have been proposed to overcome these limitations, among them glycosylation, which was used in combination with other sequence modifications to produce robust antinociception in mouse models, increased selectivity and potency at the OT receptor, and improved stability in rats.
Topics: Oxytocin; Animals; Rats; Mice; Pain; Drug Design; Glycosides; Substance-Related Disorders; Humans; Analgesics; Glycosylation; Receptors, Oxytocin
PubMed: 38886038
DOI: 10.1016/bs.mie.2024.04.016 -
The European Journal of General Practice Dec 2024Male urinary tract infections (mUTIs) are rare in primary care. The definition of mUTIs varies across countries. The therapeutic management of mUTIs in France is based...
BACKGROUND
Male urinary tract infections (mUTIs) are rare in primary care. The definition of mUTIs varies across countries. The therapeutic management of mUTIs in France is based on a 14-day course of fluoroquinolones despite a high risk of antimicrobial resistance.
OBJECTIVES
The objective of this qualitative study was to explore general practitioners' (GPs) experiences and behaviours regarding the diagnostic and therapeutic management of mUTIs.
METHODS
GPs were recruited by convenience sampling in Haute Normandie (France) and interviewed individually with semi-structured guides. GPs' experiences and behaviours were recorded and analysed using an interpretive phenomenological approach.
RESULTS
From March 2021 to May 2022, 20 GPs were included in the study. Defining a mUTI was perceived as a diagnostic challenge. A diagnosis based on clinical evidence alone was insufficient and complementary tests were required. For GPs: 'male cystitis does not exist'. A mUTI was considered an unusual disease that could reveal an underlying condition. GPs considered fluoroquinolones to be 'potent' antibiotics and treated all patients with the same 14-day course. GPs implemented improvement strategies for antibiotic stewardship and followed the guidelines using a computerised decision support system.
CONCLUSIONS
GPs' experiences of mUTIs are limited due to low exposure and variable clinical presentations in primary care, representing a diagnostic and therapeutic challenge. In order to modify GPs' antibiotic prescribing behaviours, a paradigm shift in the guidelines will need to be proposed.KEY MESSAGESDefining a male urinary tract infection represents a diagnostic challenge for GPs.A diagnosis based on clinical evidence alone is insufficient and complementary tests are required.A male urinary tract infection is an unusual disease in primary care and suggests a more serious underlying condition.
Topics: Humans; Male; Urinary Tract Infections; France; General Practitioners; Cystitis; Practice Patterns, Physicians'; Anti-Bacterial Agents; Qualitative Research; Fluoroquinolones; Middle Aged; Adult; Female; Antimicrobial Stewardship; Primary Health Care
PubMed: 38881418
DOI: 10.1080/13814788.2024.2362693 -
Journal of Medical Virology Jun 2024Viruses in human semen may be sexually transmitted via free and cell-mediated viral infection. The potential effects of semen on the infection and sexual transmission of...
Viruses in human semen may be sexually transmitted via free and cell-mediated viral infection. The potential effects of semen on the infection and sexual transmission of most viruses in semen remain largely unclear. The present study elucidated the inhibitory effects of human seminal plasma (SP) on Jurkat cell (JC)-mediated mumps virus (MuV) infection. We demonstrated that MuV efficiently infected JCs and that the JCs infected by MuV (JC-MuV) mediated MuV infection of HeLa cells. Remarkably, SP was highly cytotoxic to JCs and inhibited JC-MuV infection of HeLa cells. The cytotoxic factor possessed a molecular weight of less than 3 kDa, whereas that of the viricidal factor was over 100 kDa. The cooperation of cytotoxic and viricidal factors was required for the SP inhibition of JC-MuV infection, and prostatic fluid (PF) was responsible for both the cytotoxic and viricidal effects of SP. The cytotoxic effects we observed were resistant to the treatment of PF with boiling water, proteinase K, RNase A, and DNase I. Our results provide novel insights into the antiviral properties of SP, which may limit cell-mediated sexual viral transmission.
Topics: Humans; Mumps virus; Semen; Male; HeLa Cells; Lymphocytes; Jurkat Cells; Cell Survival; Molecular Weight
PubMed: 38874268
DOI: 10.1002/jmv.29733 -
Trials Jun 2024The TRANSLATE (TRANSrectal biopsy versus Local Anaesthetic Transperineal biopsy Evaluation) trial assesses the clinical and cost-effectiveness of two biopsy procedures...
Statistical analysis plan for the TRANSLATE (TRANSrectal biopsy versus Local Anaesthetic Transperineal biopsy Evaluation of potentially clinically significant prostate cancer) multicentre randomised controlled trial.
BACKGROUND
The TRANSLATE (TRANSrectal biopsy versus Local Anaesthetic Transperineal biopsy Evaluation) trial assesses the clinical and cost-effectiveness of two biopsy procedures in terms of detection of clinically significant prostate cancer (PCa). This article describes the statistical analysis plan (SAP) for the TRANSLATE randomised controlled trial (RCT).
METHODS/DESIGN
TRANSLATE is a parallel, superiority, multicentre RCT. Biopsy-naïve men aged ≥ 18 years requiring a prostate biopsy for suspicion of possible PCa are randomised (computer-generated 1:1 allocation ratio) to one of two biopsy procedures: transrectal (TRUS) or local anaesthetic transperineal (LATP) biopsy. The primary outcome is the difference in detection rates of clinically significant PCa (defined as Gleason Grade Group ≥ 2, i.e. any Gleason pattern ≥ 4 disease) between the two biopsy procedures. Secondary outcome measures are th eProBE questionnaire (Perception Part and General Symptoms) and International Index of Erectile Function (IIEF, Domain A) scores, International Prostate Symptom Score (IPSS) values, EQ-5D-5L scores, resource use, infection rates, complications, and serious adverse events. We describe in detail the sample size calculation, statistical models used for the analysis, handling of missing data, and planned sensitivity and subgroup analyses. This SAP was pre-specified, written and submitted without prior knowledge of the trial results.
DISCUSSION
Publication of the TRANSLATE trial SAP aims to increase the transparency of the data analysis and reduce the risk of outcome reporting bias. Any deviations from the current SAP will be described and justified in the final study report and results publication.
TRIAL REGISTRATION
International Standard Randomised Controlled Trial Number ISRCTN98159689, registered on 28 January 2021 and registered on the ClinicalTrials.gov (NCT05179694) trials registry.
Topics: Humans; Male; Prostatic Neoplasms; Biopsy; Multicenter Studies as Topic; Anesthesia, Local; Data Interpretation, Statistical; Cost-Benefit Analysis; Neoplasm Grading; Perineum; Randomized Controlled Trials as Topic; Equivalence Trials as Topic; Prostate; Rectum; Predictive Value of Tests
PubMed: 38872174
DOI: 10.1186/s13063-024-08224-4 -
PD-L1 promotes oncolytic virus infection via a metabolic shift that inhibits the type I IFN pathway.The Journal of Experimental Medicine Jul 2024While conventional wisdom initially postulated that PD-L1 serves as the inert ligand for PD-1, an emerging body of literature suggests that PD-L1 has cell-intrinsic...
While conventional wisdom initially postulated that PD-L1 serves as the inert ligand for PD-1, an emerging body of literature suggests that PD-L1 has cell-intrinsic functions in immune and cancer cells. In line with these studies, here we show that engagement of PD-L1 via cellular ligands or agonistic antibodies, including those used in the clinic, potently inhibits the type I interferon pathway in cancer cells. Hampered type I interferon responses in PD-L1-expressing cancer cells resulted in enhanced efficacy of oncolytic viruses in vitro and in vivo. Consistently, PD-L1 expression marked tumor explants from cancer patients that were best infected by oncolytic viruses. Mechanistically, PD-L1 promoted a metabolic shift characterized by enhanced glycolysis rate that resulted in increased lactate production. In turn, lactate inhibited type I IFN responses. In addition to adding mechanistic insight into PD-L1 intrinsic function, our results will also help guide the numerous ongoing efforts to combine PD-L1 antibodies with oncolytic virotherapy in clinical trials.
Topics: Animals; Female; Humans; Mice; B7-H1 Antigen; Cell Line, Tumor; Glycolysis; Interferon Type I; Lactic Acid; Neoplasms; Oncolytic Virotherapy; Oncolytic Viruses; Signal Transduction; Male
PubMed: 38869480
DOI: 10.1084/jem.20221721 -
American Journal of Cancer Research 2024The lncRNA tumor protein translationally controlled 1-antisense RNA 1 (TPT1-AS1) is known for its oncogenic role in various cancers, but its impact on the pathological...
The lncRNA tumor protein translationally controlled 1-antisense RNA 1 (TPT1-AS1) is known for its oncogenic role in various cancers, but its impact on the pathological progression of prostate cancer remains unclear. Our previous study demonstrated that the RE1-silencing transcription factor (REST) regulates neuroendocrine differentiation (NED) in prostate cancer (PCA) by derepressing specific long non-coding RNAs (lncRNAs), including TPT1-AS1. In this study, we revealed that TPT1-AS1 is overexpressed in LNCaP and C4-2B cells after IL-6 and enzalutamide treatment. By analyzing The Cancer Genome Atlas (TCGA) prostate adenocarcinoma dataset, we detected upregulated TPT1-AS1 expression in neuroendocrine-associated PCA but not in prostate adenocarcinoma. Single-cell RNA sequencing data further confirmed the increased TPT1-AS1 levels in neuroendocrine prostate cancer (NEPC) cells. Surprisingly, functional experiments indicated that TPT1-AS1 overexpression had no stimulatory effect on NED in LNCaP cells and that TPT1-AS1 knockdown did not inhibit IL-6-induced NED. Transcriptomic analysis revealed the essential role of TPT1-AS1 in synaptogenesis and autophagy activation in neuroendocrine differentiated PCA cells induced by IL-6 and enzalutamide treatment. TPT1-AS1 was found to regulate the expression of autophagy-related genes that maintain neuroendocrine cell survival through autophagy activation. In conclusion, our data expand the current knowledge of REST-repressed lncRNAs in NED in PCA and highlight the contribution of TPT1-AS1 to protect neuroendocrine cells from cell death rather than inducing NED. Our study suggested that TPT1-AS1 plays a cytoprotective role in NEPC cells; thus, targeting TPT1-AS1 is a potential therapeutic strategy.
PubMed: 38859837
DOI: 10.62347/IMBV8599