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Introduction and Importance: Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare and usually slow-growing subtype of renal cell carcinoma (RCC), with low malignant potential. There is scant knowledge in the literature of this rare subtype of renal cell carcinoma., Case Presentation: We present the case of a 56 year old with an aggressive recurrent metastatic MTSCC para-aortic lymph node treated with surgical excision., Clinical Discussion: This case is unusual due to its recurrent and aggressive metastatic nature and not typical for this rare subtype of renal cell carcinoma., Conclusion: Metastatic and recurrent renal mucinous tubular and spindle cell carcinoma is a very rare entity. Our case report aims to add to the limited knowledge in the literature on this rare malignancy., Competing Interests: Conflict of interest statement There is no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction and Importance: Renal transplant recipients have a higher risk for developing cancers compared to the general population due to high-dose immunosuppression. The risk of renal cell carcinoma (RCC) in native kidneys is 7-fold greater than the general population and development of RCC in an allograft kidney is extremely rare. We report the diagnosis and management of a large RCC in an allograft renal transplant and metastatic disease in a regional lymph node., Case Presentation: A 46 year old male patient with a history of simultaneous pancreas and kidney transplant presented with visible haematuria. His pancreas allograft continued to function well however following severe BK nephritis his renal transplant failed. A CT urogram demonstrated a 6 cm contrast enhancing mass in the failed renal transplant and an enlarged pelvic lymph node. He underwent a transplant nephrectomy with excision of the metastatic lymph node deposit., Clinical Discussion: We report the diagnosis and management of a large RCC in an allograft renal transplant and metastatic disease in a regional lymph node. There is currently no guidelines on the management of allograft RCC., Conclusion: Our case report shows that surgical excision of a large RCC in an allograft renal transplant is possible., Competing Interests: Declaration of competing interest Nothing to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Penile cancer is a rare urological malignancy with an age-standardised incidence of 0.8 per 100,000 person-years [1]. Given this low incidence it has been suggested that centralised care may improve patient outcomes in relation to phallus sparing surgery and nodal assessment [2]. We aim to assess the outcomes after 5-years of national centralisation of penile cancer care., Methods: A retrospective analysis of prospectively collected data was performed. All patients undergoing penile cancer surgery from January 2018 to December 2022 following centralisation of care were included. The primary outcome was proportion of phallus sparing procedures performed. Secondary outcomes were patient characteristics, histologic outcomes and procedures performed., Results: 124 patients underwent surgery in the study period. Mean age was 64.49 (±13.87). Overall, 82.3% of patients underwent phallus sparing surgery. This remained stable over the 5-year period from 2018 to 2022 ​at 92%, 85%, 76%, 79% and 78% respectively (p ​= ​0.534). 62.7% had reconstruction performed, including split-thickness skin graft neoglans formation, (57.8% [n ​= ​37]), preputial flap (32.8% [n ​= ​21]), glans resurfacing (4.7% [n ​= ​3]), shaft advancement flap (1.6% [n ​= ​1]), penile shaft skin graft (1.6% [n ​= ​1]), and partial penectomy with urethral centralisation (1.6% [n ​= ​1]). Phallus preservation was not affected by positive nodal status (OR 0.75 [95% CI 0.249-2.266], p ​= ​0.564) or T-stage ≥1b (OR 0.51 [95% CI 0.153-1.711], p ​= ​0.276). There has been a significant reduction in Nx nodal status from 64% in 2017 to 15% in 2021 (p ​= ​0.009)., Conclusion: Centralisation of treatment for rare malignancies such as penile cancer may improve oncologic outcomes and rates of phallus preservation. This study has shown centralisation to has a high rate of phallus preservation. Further long-term analysis of outcomes in Ireland is required., Competing Interests: Declaration of competing interest The author's declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.)

Background: Penile fractures are uncommon urological emergencies which occur when there has been a breach in the tunica albuginea of the corpora cavernosum that may be unilateral and bilateral and can extend to involve the urethra., Aim: To assess the management and outcomes of penile fractures in a single institution in Ireland., Methods: A retrospective review of the emergency theatre logbooks was performed between 2011 and 2021 to identify patients who had undergone an exploration for a suspected penile fracture., Outcomes: Seventeen patients were initially identified on review of theatre logbooks as having an exploration for a suspected penile fracture. Two patients were excluded from the study due to a lack of clinical notes being available. A further 4 patients on chart review were found to not have a penile fracture at exploration., Results: Eleven patients had a confirmed penile fracture intra-operatively, four of whom had an associated urethral injury. Nine (9/11) patients had preserved normal erections post-operatively documented on follow-up; two, however, reported erectile dysfunction requiring phosphodiesterase inhibitors., Clinical Implications: Our study supports urgent surgical exploration for penile fractures to ensure good functional outcomes., Strengths and Limitations: This is a retrospective review of theatre logbooks to identify patients with a suspected penile fracture., Conclusion: The results of our cohort show a good outcome of erectile function following surgical repair of a penile fracture (9/11; 82%). Four patients (4/11; 36%) had a urethral injury diagnosed intra-operatively, one of whom required a formal urethroplasty., (© 2023. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Purpose: Acute epididymo-orchitis (AEO) is a common urological condition characterised by pain and swelling of the epididymis which can affect men of any age. The aetiology and to some extent the management of the patient differ between paediatric and young and older adult groups., Methods: A retrospective analysis was performed at the University Hospital Limerick from 2012 to 2016. Hospital In-Patient Enquiry (HIPE) data were obtained for all patients diagnosed with orchitis, epididymitis, epididymo-orchitis or testicular abscess over this 5-year period., Results: 140 patients were identified, the age range was 0-89, median age 35.6. These were then split into 3 clinical groups, pre-pubertal (Group 1, 0-15-year-olds), sexually active young men (Group 2a, 16-35-year-olds) and men over 35 (Group 2b). Nine patients had an abscess on ultrasound investigation. There was a significant correlation between the presence of an abscess and the need for an orchidectomy (2 patients, P = 0.035). Two patients were reported as having an atrophic testis following AEO and both were in Group 2b., Conclusion: Overall, 7/131 (5%) patients had loss or atrophy of a testicle following an episode of AEO. Nineteen patients had further readmissions with AEO (14%)., (© 2023. The Author(s).)

Introduction: The Irish people were put on lockdown in mid-March 2020 due to concern of the spread of coronavirus. With these societal changes came a notable reduction in emergency department attendance. Our aim was to analyse emergency urological procedures performed during the COVID-19 era versus the previous year., Methods: A retrospective review of theatre logbooks was undertaken comparing numbers of emergency urological procedures performed between 1 March 2020 and 31 May 2020 (i.e. the COVID-19 era) with the corresponding 3-month period in 2019., Results: A total of 173 cases were analysed between the two time periods. Similar overall numbers of cases were performed in 2019 (n = 90) and 2020 (n = 83). In particular, similar patient case numbers are also noted in both scrotal explorations (13 vs 9) and ureteric stone surgeries (69 vs 70). However, orchidectomies for testicular cancers were reduced by 63% (3/8). On further analysis of the scrotal exploration group, only 3 were performed in the period after lockdown regulations were instated., Conclusion: Whilst patients with ureteric colic continue to present, those with acute testis pain requiring exploration attended less frequently, raising the possibility of undiagnosed testicular torsion in the community., (© 2021. The Author(s).)

Background: Decreased galactocerebrosidase (GALC) enzyme activity is causative for Krabbe disease, a lysosomal storage disorder with devastating neurodegenerative consequences. Quantitative fluorimetric assays for GALC activity in isolated blood and skin cells have been described; however, no such assay has been described using dried blood spot (DBS) specimens., Methods: GALC enzyme activity was measured quantitatively using fluorescence from a novel glycosidic substrate: carboxy derived from 6-hexadecanoylamino-4-methylumbelliferone. GALC activity was demonstrated on newborn DBS specimens, known Krabbe disease patient specimens, proficiency testing and quality control samples., Results: We present data on characterization of the novel substrate and assay, including pH optimization and enzyme kinetics using a fluorimetric profile. Single and multi-day precision analyses revealed tight analytical measurements with %CV ranging from 5.2% to 14.1%. GALC enzyme activity was linear over the range of 0.31 - 12.04 μmol/l/h with a limit of detection of 0.066 μmol/l/h. Our results with this assay show a clear discrimination between GALC activities in samples from Krabbe disease patients versus presumed normal newborn samples., Conclusions: A fluorimetric assay for GALC enzyme activity measurement on dried blood spot specimens is feasible. Improvements to the assay including novel substrate design, increased substrate concentration and removal of sodium chloride maximize the specificity of the assay and minimize interference from β-galactosidase., Competing Interests: All the authors from Baebies have stocks or stock options in Baebies, Inc. Dr. Eckhardt was an employee of Advanced Liquid Logic, Inc. and is now an employee of Illumina, Inc. which acquired Advanced Liquid Logic, Inc., (© 2019 The Authors.)

Background: Male urethral stricture disease is a challenging condition with a propensity for recurrence following endoscopic management. In recent years, earlier definitive urethral reconstruction has been advocated through international guidelines, prompted by series suggesting the underutilization of urethroplasty at rates of 0.6-0.8%. However, little local data exists to characterize our urethral stricture patients and we aimed to characterize the management of patients with urethral stricture disease presenting over a 10-year period to a single regional centre., Methods: Patients with urethral stricture disease and admitted to a regional health service were identified. Retrospective chart review was undertaken for patients detailing basic demographics, stricture characteristics, clinical management and follow up., Results: We identified 360 patients with median age 69 years (interquartile range 56-77). A total of 191 (53%) presented with lower urinary tract symptoms, 122 (34%) urethral strictures were incidental, and 13% presented in urinary retention. Bulbar urethral strictures were the commonest strictures at 40% with most being spontaneous or idiopathic (67%). A total of 339 patients had treatment during their first admission, 48% of patients had subsequent treatment on a second episode, and over 20% had a third or subsequent treatment. Only 21 (5.8%) underwent urethroplasty. Urethral dilatation and optical urethrotomy were most commonly performed (54%). With follow up 19 months (interquartile range 2-56), 205 (57%) were voiding, 38 (11%) were performing intermittent catheterization, and 59 were catheterized permanently., Conclusion: Definitive urethral reconstruction appears underutilized in our cohort of patients. A high proportion of incidentally presenting urethral strictures emphasizes the importance of wider education to optimize patient outcomes., (© 2019 Royal Australasian College of Surgeons.)

Background: Newborn screening for lysosomal storage diseases (LSDs) has been gaining considerable interest owing to the availability of enzyme replacement therapies. We present a digital microfluidic platform to perform rapid, multiplexed enzymatic analysis of acid α-glucosidase (GAA) and acid α-galactosidase to screen for Pompe and Fabry disorders. The results were compared with those obtained using standard fluorometric methods., Methods: We performed bench-based, fluorometric enzymatic analysis on 60 deidentified newborn dried blood spots (DBSs), plus 10 Pompe-affected and 11 Fabry-affected samples, at Duke Biochemical Genetics Laboratory using a 3-mm punch for each assay and an incubation time of 20 h. We used a digital microfluidic platform to automate fluorometric enzymatic assays at Advanced Liquid Logic Inc. using extract from a single punch for both assays, with an incubation time of 6 h. Assays were also performed with an incubation time of 1 h., Results: Assay results were generally comparable, although mean enzymatic activity for GAA using microfluidics was approximately 3 times higher than that obtained using bench-based methods, which could be attributed to higher substrate concentration. Clear separation was observed between the normal and affected samples at both 6- and 1-h incubation times using digital microfluidics., Conclusions: A digital microfluidic platform compared favorably with a clinical reference laboratory to perform enzymatic analysis in DBSs for Pompe and Fabry disorders. This platform presents a new technology for a newborn screening laboratory to screen LSDs by fully automating all the liquid-handling operations in an inexpensive system, providing rapid results.

Single-nucleotide polymorphisms (SNP) are the most common form of sequence variation in the human genome. Large-scale studies demand high-throughput SNP genotyping platforms. Here we demonstrate the potential of encoded nanowires for use in a particles-based universal array for high-throughput SNP genotyping. The particles are encoded sub-micron metallic nanorods manufactured by electroplating inert metals such as gold and silver into templates and releasing the resulting striped nanoparticles. The power of this technology is that the particles are intrinsically encoded by virtue of the different reflectivity of adjacent metal stripes, enabling the generation of many thousands of unique encoded substrates. Using SNP found within the cytochrome P450 gene family, and a universal short oligonucleotide ligation strategy, we have demonstrated the simultaneous genotyping of 15 SNP; a format requiring discrimination of 30 encoded nanowires (one per allele). To demonstrate applicability to real-world applications, 160 genotypes were determined from multiplex PCR products from 20 genomic DNA samples.

The anti-allograft immune response may have a cellular and a humoral component. Lymphocytotoxic antibodies (Ab) and anti-human leucocyte antigen (HLA) Ab present before kidney transplantation carry an enhanced risk of acute rejection. Current immunosuppressive drugs act predominantly upon the cellular immune pathway which may leave unopposed the humoral mechanisms of anti-allograft response. We studied the production of lymphocytotoxic Ab and anti-HLA Ab after kidney transplantation under different drug therapies. Two hundred and sixty-four consecutive kidney transplant recipients treated with different immunosuppressive drugs, either stable and or with previous acute rejection or acute urologic obstruction, entered this study. Lymphocytotoxic Ab and anti-HLA Ab were evaluated by complement-dependent cytotoxicity and by ELISA. Ab donor-specificity was determined by flow cytometry. Both lymphocytotoxic Ab and anti-HLA Ab were significantly increased in acute rejection whatever the immunosuppressive regimen and almost significantly in urologic obstruction treated with azathioprine (AZA) groups. The presence of antidonor-specific Ab was associated with a significantly higher rate of graft loss. Mycophenolate mofetil (MMF) therapy significantly down-regulated Ab synthesis in all patients groups when compared with AZA. The development of humoral antidonor response post-transplantation is associated with a dismal graft prognosis. This is the first report that acute urologic obstruction may be followed by unspecific lymphocytotoxic and anti-HLA Ab synthesis, surmising that a protracted obstruction may promote renal fibrosis through antibody mediation. The significant down-regulation of the humoral response by MMF when compared with AZA may herald a lower risk to mount a chronic rejection process.

We have developed striped metal nanoparticles, Nanobarcodes particles, which can act as encoded substrates in multiplexed assays. These particles are metallic, encodeable, machine-readable, durable, submicron-sized tags. The power of this technology is that the particles are intrinsically encoded by virtue of the difference in reflectivity of adjacent metal stripes. This chapter describes protocols for the attachment of biological molecules, and the subsequent use of the Nanobarcodes particles in bioassays.

In this paper we describe a molecular beacon format assay in which encoded nanowire particles are used to achieve multiplexing. We demonstrate this principle with the detection of five viral pathogens; Hepatitis A virus, Hepatitis C virus, West Nile Virus, Human Immune Deficiency virus and Severe Acute Respiratory Syndrome virus. Oligonucleotides are designed complementary to a target sequence of interest containing a 3' universal fluorescence dye. A 5' thiol causes the oligonucleotides to self-assemble onto the metal nanowire. The single-stranded oligonucleotide contains a self-complementary hairpin stem sequence of 10 bases that forces the 3' fluorophore to come into contact with the metallic nanowire surface, thereby quenching the fluorescence. Upon addition of target DNA, there is hybridization with the complementary oligonucleotides. The resulting DNA hybrid is rigid, unfolds the hairpin structure, and causes the fluorophore to be moved away from the surface such that it is no longer quenched. By using differently encoded nanowires, each conjugated with a different oligonucleotide sequence, multiplexed DNA assays are possible using a single fluorophore, from a multiplexed RT-PCR reaction., (© Humana Press Inc 2005.)

In this report, we present data demonstrating that cylindrical metallic particles, with various submicrometer striping patterns, may be readily distinguished in an optical microscope. Accurate particle identification is discussed relative to synthesis reproducibility and the limitations of optical microscopes. Results from a library of these particles, of which over 100 different striping patterns have been produced, are presented. For these particles, made with Au and Ag stripes, more than 70 patterns may be identified with greater than 90% accuracy. The ability to chemically modify the surface of these particles, making them useful for bioanalytical measurements, is also demonstrated. Finally, we discuss improvements in our manufacturing and identification processes that will lead to both larger numbers of striping patterns and improved identification accuracy.

Two new algorithms for automated processing of liquid chromatography/mass spectrometry (LC/MS) data are presented. These algorithms were developed from an analysis of the noise and artifact distribution in such data. The noise distribution was analyzed by preparing histograms of the signal intensity in LC/MS data. These histograms are well fit by a sum of two normal distributions in the log scale. One new algorithm, median filtering, provides increased performance compared to averaging adjacent scans in removing noise that is not normally distributed in the linear scale. Another new algorithm, vectorized peak detection, provides increased robustness with respect to variation in the noise and artifact distribution compared to methods based on determining an intensity threshold for the entire dataset. Vectorized peak detection also permits the incorporation of existing algorithms for peak detection in ion chromatograms and/or mass spectra. The application of these methods to LC/MS spectra of complex biological samples is described., (Copyright 2002 John Wiley & Sons, Ltd.)

The goals of precise diagnosis, prevention and treatment of disease can be realized through the discovery of biological markers. Spectroscopic tools can simultaneously detect and quantify multiple small molecule and macromolecular components of biological samples, and are therefore ideal methods for the discovery of previously uncharacterized markers. However, the identification of meaningful spectral features is complicated by the lack of foreknowledge of the molecular nature of a disease, spectral noise and biological variability that is uncorrelated with the disease state. Pattern recognition techniques, both statistical and machine-learning, have been increasingly used in recent years with spectroscopic data to identify markers and classify patients into disease subsets. This review summarizes recent developments, limitations and future prospects in the use of data mining techniques with magnetic resonance spectroscopy, mass spectrometry and optical spectroscopy for the discovery of biomarkers.