Applications of Urinary Extracellular Vesicles in the Diagnosis and Active Surveillance of Prostate Cancer.

Prostate cancer is the most common non-cutaneous cancer among men in the UK, causing significant health and economic burdens. Diagnosis and risk prognostication can be challenging due to the genetic and clinical heterogeneity of prostate cancer as well as uncertainties in our knowledge of the underlying biology and natural history of disease development. Urinary extracellular vesicles (EVs) are microscopic, lipid bilayer defined particles released by cells that carry a variety of molecular cargoes including nucleic acids, proteins and other molecules. Urine is a plentiful source of prostate-derived EVs. In this narrative review, we summarise the evidence on the function of urinary EVs and their applications in the evolving field of prostate cancer diagnostics and active surveillance. EVs are implicated in the development of all hallmarks of prostate cancer, and this knowledge has been applied to the development of multiple diagnostic tests, which are largely based on RNA and miRNA. Common gene probes included in multi-probe tests include PCA3 and ERG, and the miRNAs miR-21 and miR-141. The next decade will likely bring further improvements in the diagnostic accuracy of biomarkers as well as insights into molecular biological mechanisms of action that can be translated into opportunities in precision uro-oncology.

A case report of bladder leiomyoma: an unusual bladder tumour.

Leiomyomas are benign mesenchymal tumours that rarely arise in the bladder. We present a case of a 53-year-old female who was incidentally diagnosed with a bladder leiomyoma identified on CT imaging performed for investigation of a urachal remnant. We discuss the investigation and management of this lesion in the context of modern urology practice. An awareness of this unusual tumour is important for urologists, who may encounter similar cases in their general urology practice.

In vitro characterisation of ultrasound-induced heating effects in the mother and fetus: A clinical perspective.

INTRODUCTION: The quantification of heating effects during exposure to ultrasound is usually based on laboratory experiments in water and is assessed using extrapolated parameters such as the thermal index. In our study, we have measured the temperature increase directly in a simulator of the maternal-fetal environment, the 'ISUOG Phantom', using clinically relevant ultrasound scanners, transducers and exposure conditions. METHODS: The study was carried out using an instrumented phantom designed to represent the pregnant maternal abdomen and which enabled temperature recordings at positions in tissue mimics which represented the skin surface, sub-surface, amniotic fluid and fetal bone interface. We tested four different transducers on a commercial diagnostic scanner. The effects of scan duration, presence of a circulating fluid, pre-set and power were recorded. RESULTS: The highest temperature increase was always at the transducer-skin interface, where temperature increases between 1.4°C and 9.5°C were observed; lower temperature rises, between 0.1°C and 1.0°C, were observed deeper in tissue and at the bone interface. Doppler modes generated the highest temperature increases. Most of the heating occurred in the first 3 minutes of exposure, with the presence of a circulating fluid having a limited effect. The power setting affected the maximum temperature increase proportionally, with peak temperature increasing from 4.3°C to 6.7°C when power was increased from 63% to 100%. CONCLUSIONS: Although this phantom provides a crude mimic of the in vivo conditions, the overall results showed good repeatability and agreement with previously published experiments. All studies showed that the temperature rises observed fell within the recommendations of international regulatory bodies. However, it is important that the operator should be aware of factors affecting the temperature increase.

Balloon bursting: transurethral puncture of a Foley catheter balloon.

We describe the case of a 76-year-old male who presented with a retained Foley catheter. On the initial attempt to deflate the Foley catheter with a syringe attached to the inflation port, no fluid was aspirated. Using a flexible cystoscope passed alongside the catheter, the balloon was punctured under direct vision with an intravesical needle passed through the cystoscope working channel. We discuss this innovative and safe method for balloon puncture via the transurethral route that can be achieved in the urology outpatient or endoscopy suite.

Not such a small diagnosis: small cell carcinoma of the prostate.

Small cell carcinoma (SCC) is an aggressive malignancy most commonly described in the lung. We present a case of a 61-year-old male who presented with a neck swelling and was subsequently found to have metastatic SCC of the prostate. Clinicians should be aware that it metastasizes early. Unlike conventional prostate adenocarcinoma, it is not a prostate-specific antigen (PSA) secreting tumor hence serum levels do not correlate with disease severity, and a low PSA reading may give false reassurance. In the future, further studies on genomic typing and novel targeted therapies may achieve better clinical outcomes for patients with this aggressive type of prostate cancer.

Potts puffy tumour: a rare but important diagnosis.

Potts puffy tumour (PPT) is a subperiosteal abscess arising from frontal bone osteomyelitis. We present a case of a 75-year-old lady with headache and a forehead swelling who was initially treated for sinusitis and giant cell arteritis in a primary care setting, but failed to improve. Following clinical deterioration and further investigation, CT appearances were consistent with a diagnosis of PPT and an extra-axial collection. Needle decompression, frontal trephine and endoscopic frontal sinusotomy were performed and intraoperative swabs cultured Streptococcus constellatus PPT is an unusual clinical entity that benefits from prompt antibiotic and surgical management, and therefore early recognition is paramount. We highlight that PPT should be a differential diagnosis in all patients presenting with forehead or frontal swelling. Use of radiological imaging (CT/MRI) is necessary to not only confirm a diagnosis of PPT but to identify further intracranial complications, which can be life-threatening.

Ischemia-reperfusion injury in renal transplantation: 3 key signaling pathways in tubular epithelial cells.

Renal ischemia-reperfusion injury (IRI) is a significant clinical challenge faced by clinicians perioperatively in kidney transplantation. Recent work has demonstrated the key importance of transmembrane receptors in the injured tubular epithelial cell, most notably Toll-like receptors, activated by exogenous and endogenous ligands in response to external and internal stresses. Through sequential protein-protein interactions, the signal is relayed deep into the core physiological machinery of the cell, having numerous effects from upregulation of pro-inflammatory gene products through to modulating mitochondrial respiration. Inter-pathway cross talk facilitates a co-ordinated response at an individual cellular level, as well as modulating the surrounding tissue's microenvironment through close interactions with the endothelium and circulating leukocytes. Defining the underlying cellular cascades involved in IRI will assist the identification of novel interventional targets to attenuate IRI with the potential to improve transplantation outcomes. We present a focused review of 3 key cellular signalling pathways in the injured tubular epithelial cell that have been the focus of much research over the past 2 decades: toll-like receptors, sphingosine-1-phosphate receptors and hypoxia inducible factors. We provide a unique perspective on the potential clinical translations of this recent work in the transplant setting. This is particularly timely with the recent completion of phase I and ongoing phase 2 clinical trials of inhibitors targeting specific components of these signaling cascades.

The administration of argon during ex vivo normothermic perfusion in an experimental model of kidney ischemia-reperfusion injury.

BACKGROUND: Argon has shown potential as an organoprotective agent in numerous models of ischemia-reperfusion injury (IRI). The aim of this study was to evaluate the effects of argon gas during ex vivo normothermic perfusion (EVNP) in an experimental porcine model of kidney IRI. MATERIALS AND METHODS: After a warm ischemia time of 15 min and 17 h of static cold storage, porcine kidneys underwent 1 h of EVNP using leukocyte-depleted blood. During EVNP, kidneys were perfused with a gas composition either of 70% argon (n = 6), 70% nitrogen control (n = 6), or standard 95% oxygen (n = 6) balanced with 5% carbon dioxide. After EVNP, kidneys were reperfused with whole blood under standard conditions for 3 h to assess renal function and injury. RESULTS: During 1-h EVNP, the mean renal blood flow was numerically higher in the argon group (49.2 ± 16.2 mL/min/100 g; P = 0.320) compared with the nitrogen and oxygen groups (42.9 ± 18.64 and 37.71 ± 7.0 mL/min/100 g, respectively). Other measures of renal function and hemodynamics were not significantly different between the argon and control groups during this period. During reperfusion, no significant differences were found in functional parameters or inflammatory markers (P < 0.05). Histologic analysis revealed no significant change in morphology or hypoxia-inducible factor-1 alpha staining between gaseous groups. Nuclear hypoxia-inducible factor-1 alpha staining was observed only after 3 h of reperfusion. CONCLUSIONS: Our findings suggest that using 70% argon during 1 h of EVNP does not mediate a measurable organoprotective effect in an experimental porcine model of IRI.

Physiological and emotional responses to subjective social evaluative threat in daily life.

BACKGROUND AND OBJECTIVES: This study examined concurrent and delayed emotional and cardiovascular correlates of naturally occurring experiences with subjective social evaluative threat (SSET) and tested whether individual differences in social interaction anxiety moderated those associations. METHODS: Sixty-eight participants wore ambulatory blood pressure monitors for three days. Following each blood pressure reading, participants reported on SSET and negative emotions, yielding 1770 momentary measures. RESULTS: Multilevel modeling suggested that reports of greater SSET uniquely predicted elevations in anxiety and embarrassment, with elevations in anxiety, embarrassment, and shame extending to the hour following SSET. Reports of concurrent and previous-hour SSET also predicted cardiovascular elevations. Linkages between SSET and anxiety and shame, but not cardiovascular measures, were moderated by social interaction anxiety. Those higher in social interaction anxiety showed especially strong associations between SSET and both concurrent and delayed anxiety and greater delayed shame. CONCLUSIONS: This research suggests an important role for anxiety, embarrassment, and shame as emotional consequences of naturally occurring evaluative threat, especially for those who are more socially anxious. Further, this work replicates other naturalistic studies that have documented increased blood pressure at times of SSET and extends that work by documenting cardiovascular responses into the following hour.

Length of hospital stay is shorter in South Asian patients with acute pulmonary embolism.

Pulmonary embolism (PE) is a common diagnosis in UK hospitals and confers a significant hospital stay (LOS). There is very little evidence concerning ethnic variations on LOS in patients with PE. We sought to investigate ethnic variations in LOS in a large sample of 3440 patients with PE from 2000 to 2013 across seven hospitals in the north west of UK. We found that South Asian patients have significantly lower LOS compared with Caucasian patients. We discuss possible reasons for, and implications of, this finding.

Vasa nervorum in rat major pelvic ganglion are innervated by nitrergic nerve fibers.

INTRODUCTION: The vasa nervorum comprises a network of small diameter blood vessels that provide blood supply to nerves and ganglia. The cell bodies of autonomic nerves innervating the urogenital organs are housed in the major pelvic ganglia (MPG) in rats. The vasa nervorum of rat MPG have not been characterized previously, and it is not known whether these blood vessels are innervated by neuronal nitric oxide synthase (nNOS) containing nitrergic nerves. AIM: To characterize the blood vessels in and around the rat MPG and to assess their nitrergic innervation. MAIN OUTCOME MEASURES: Characterization of small blood vessels in and around the rat MPG and expression of nNOS in nerve fibers around those blood vessels. METHODS: MPG were obtained from healthy Sprague Dawley rats, fixed in paraformaldehyde, frozen and sectioned using a cryostat. The blood vessels and their nitrergic innervation were assessed with immunohistochemistry using antibodies against alpha-smooth muscle actin (smooth muscle marker), CD31 (endothelial marker), collagen IV (basal membrane marker) and nNOS. The immunofluorescence was imaged using a laser scanning confocal microscope. RESULTS: The neuronal cell bodies were contained within a capsule in the MPG. Blood vessels were observed within the capsule of the MPG as well as outside the capsule. The blood vessels inside the capsule were CD31-positive capillaries with no smooth muscle staining. Outside the capsule capillaries, arterioles and venules were observed. The extra-capsular arterioles and venules, but not the capillaries were innervated by nNOS-positive nerve fibers. CONCLUSIONS: This study, to our knowledge, is the first to demonstrate the blood vessel distribution pattern and their nitrergic innervation in the rat MPG. While similar studies in human pelvic plexus are warranted, these results suggest that the blood flow in the MPG may be regulated by nitrergic nerve fibers and reveal a reciprocal relationship between nerves and blood vessels.