Artificial intelligence in the diagnosis, treatment and prevention of urinary stones.

PURPOSE OF REVIEW: There has a been rapid progress in the use of artificial intelligence in all aspects of healthcare, and in urology, this is particularly astute in the overall management of urolithiasis. This article reviews advances in the use of artificial intelligence for the diagnosis, treatment and prevention of urinary stone disease over the last 2 years. Pertinent studies were identified via a nonsystematic review of the literature performed using MEDLINE and the Cochrane database. RECENT FINDINGS: Twelve articles have been published, which met the inclusion criteria. This included three articles in the detection and diagnosis of stones, six in the prediction of postprocedural outcomes including percutaneous nephrolithotomy and shock wave lithotripsy, and three in the use of artificial intelligence in prevention of stone disease by predicting patients at risk of stones, detecting the stone type via digital photographs and detecting risk factors in patients most at risk of not attending outpatient appointments. SUMMARY: Our knowledge of artificial intelligence in urology has greatly advanced in the last 2 years. Its role currently is to aid the endourologist as opposed to replacing them. However, the ability of artificial intelligence to efficiently process vast quantities of data, in combination with the shift towards electronic patient records provides increasingly more 'big data' sets. This will allow artificial intelligence to analyse and detect novel diagnostic and treatment patterns in the future.

First experience in the UK of treating women with recurrent urinary tract infections with the bacterial vaccine Uromune®.

OBJECTIVES: To determine the effectiveness of Uromune® in preventing recurrent urinary tract infections (UTIs) in women. PATIENTS AND METHODS: A total of 77 women with microbiology-proven recurrent UTIs were given Uromune sublingual vaccine for a period of 3 months. Time to first UTI recurrence since treatment and adverse events were prospectively recorded in a follow-up period of up to 12 months. RESULTS: Of the 77 women, 75 completed the treatment. Of the 75 women who completed treatment, 59 (78%) had no subsequent UTIs in the follow-up period. Prior to treatment, all women had experienced a minimum of three or more episodes of UTI during the preceding 12 months. Proportionally, the majority of recurrences occurred in postmenopausal women. One patient had to stop treatment because of an adverse event (rash over face and neck). CONCLUSION: This prospective study suggests that Uromune is safe and effective at preventing UTIs in women. Further research is required in larger groups of patients for longer treatment times. An international double-blind randomized control trial comparing Uromune with placebo is currently underway.

Does the introduction of prostate multiparametric magnetic resonance imaging into the active surveillance protocol for localized prostate cancer improve patient re-classification?

OBJECTIVES: To determine whether replacement of protocol-driven repeat prostate biopsy (PB) with multiparametric magnetic resonance imaging (mpMRI) ± repeat targeted prostate biopsy (TB) when evaluating men on active surveillance (AS) for low-volume, low- to intermediate-risk prostate cancer (PCa) altered the likelihood of or time to treatment, or reduced the number of repeat biopsies required to trigger treatment. PATIENTS AND METHODS: A total of 445 patients underwent AS in the period 2010-2016 at our institution, with a median (interquartile range [IQR]) follow-up of 2.4 (1.2-3.7) years. Up to 2014, patients followed a 'pre-2014' AS protocol, which incorporated PB, and subsequently, according to the 2014 National Institute for Health and Care Excellence (NICE) guidelines, patients followed a '2014-present' AS protocol that included mpMRI. We identified four groups of patients within the cohort: 'no mpMRI and no PB'; 'PB alone'; 'mpMRI ± TB'; and 'PB and mpMRI ± TB'. Kaplan-Meier plots and log-rank tests were used to compare groups. RESULTS: Of 445 patients, 132 (30%) discontinued AS and underwent treatment intervention, with a median (IQR) time to treatment of 1.55 (0.71-2.4) years. The commonest trigger for treatment was PCa upgrading after mpMRI and TB (43/132 patients, 29%). No significant difference was observed in the time at which patients receiving a PB alone or receiving mpMRI ± TB discontinued AS to undergo treatment (median 1.9 vs 1.33 years; P = 0.747). Considering only those patients who underwent repeat biopsy, a greater proportion of patients receiving TB after mpMRI discontinued AS compared with those receiving PB alone (29/66 [44%] vs 32/87 [37%]; P = 0.003). On average, a single set of repeat biopsies was needed to trigger treatment regardless of whether this was a PB or TB. CONCLUSIONS: Replacing a systematic PB with mpMRI ±TB as part of an AS protocol increased the likelihood of re-classifying patients on AS and identifying men with clinically significant disease requiring treatment. mpMRI ±TB as part of AS thereby represents a significant advance in the oncological safety of the AS protocol.

2ME2 increase radiation-induced apoptosis of keloid fibroblasts by targeting HIF-1α in vitro.

BACKGROUND: Radiation therapy is considered to be a treatment for keloid scarring; however, radioresistance has been shown to be a serious impediment to treatment efficacy. There is therefore a need for the discovery of novel critical molecular targets whose inhibition might enhance the radiotherapeutic response. An elevated level of hypoxia inducible factor (HIF)-1α expression after radiation therapy in keloid fibroblasts has been demonstrated in our recent experiments. Therefore, we suggested there was a possible close relationship between HIF-1α and keloid radioresistance. The current study aimed to investigate whether target HIF-1α may enhance the radiotherapeutic efficacy of keloids. METHODS: 2-methoxyestradiol (2ME2) was applied to inhibit HIF-1α expression, and the treatment results were assessed by cell proliferation, apoptosis and radiosensitivity. A lentivirus-mediated small interfering RNA (siRNA) transduction method was used to block the expression of HIF-1α gene. RESULTS: Both mRNA and protein levels can be effectively inhibited after the knockdown of HIF-1α, leading to a significant increase of radiation-induced apoptosis in keloid fibroblasts. Our experiment also demonstrated that 2ME2 could effectively inhibit the protein expression of HIF-1α, which significantly increased the late stage of radiation-induced apoptosis of keloid fibroblasts. CONCLUSIONS: The present study indicates that HIF-1α might serve as a therapeutic target for keloids. Furthermore, suppression of HIF-1α by 2ME2 may be a promising therapeutic adjuvant in radiation therapy for keloids.

Ischaemic and inflammatory injury in renal graft from brain death donation: an update review.

Renal transplantation remains an important therapy in treating renal failure and can be considered to be a curative treatment. The demand for renal grafts outstrips supply available each year, making it increasingly important to look at improving the treatment of both renal grafts and recipients, and thereby improving patient outcomes and increasing the pool of potential donor grafts. Important to this, however, is knowledge of the underlying mechanisms leading to damage to the graft and rejection from the recipient. This includes ischaemia and consequently the priming of the organ during storage for ischaemia reperfusion injury (IRI) on implantation and the importance of the innate immune system which can be activated via multiple pathways, often via TLR-4, and the consequent production of danger-associated molecular patterns. This makes the time period involving both explantation and storage an important therapeutic window for improving outcomes. Other windows explored include treatment of IRI and improvement in immunosuppressive therapy. The multiple windows of potential therapeutic input have spawned a large body of work exploring both the underlying mechanisms and also how to exploit these mechanisms to improve overall outcomes and to allow for more marginal organs to be used.

Transient regional hypothermia applied to a traumatic limb attenuates distant lung injury following blast limb trauma.

OBJECTIVES: Explosive traumatic injury to an extremity may lead to both local and distant organ injury. Regional traumatic tissue hypothermia has been reported to offer systemic protection; here we investigated the protective effects of regional limb hypothermia on local tissue trauma and the lungs. Furthermore, the optimal duration of regional traumatic limb hypothermic treatment was also evaluated. DESIGN: Prospective, controlled, animal study. SETTING: University research laboratory. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: Anesthetized rats were randomized to sham, blast limb trauma, sham and regional hypothermia for 30 minutes, and blast limb trauma and regional hypothermia for 30 minutes, 60 minutes, and 6 hours. Blast limb trauma was created using chartaceous electricity detonators. MEASUREMENTS AND MAIN RESULTS: Distant lung and local tissue injury following blast limb trauma were attenuated by regional traumatic limb hypothermic treatment for 30 minutes, 60 minutes, and 6 hours reflected by reduced lung histopathological changes and water content. Regional traumatic limb hypothermic treatment for 60 minutes and 6 hours failed to further attenuate distant lung and local tissue injury compared with regional traumatic limb hypothermic treatment for 30 minutes. Inhibition of cystathionine gamma-lyase/hydrogen sulfide was reduced by regional traumatic limb hypothermic treatment for 30 minutes in blast limb trauma rats. A surrogate of neutrophil accumulation, myeloperoxidase activity, and release of tumor necrosis factor-α and interleukin-6 were also attenuated by regional traumatic limb hypothermic treatment for 30 minutes in blast limb trauma rats. Oxidative stress was alleviated by regional traumatic limb hypothermic treatment for 30 minutes evidenced by reduction of hydrogen peroxide and malondialdehyde and an increase of superoxide dismutase and glutathione in blast limb trauma rats. CONCLUSIONS: Our data indicate that regional traumatic limb hypothermic treatment for 30 minutes offers both local protection for traumatic tissue and systemic protection for the lungs, which is likely associated with restoration of the cystathionine gamma-lyase/hydrogen sulfide pathway and inhibition of the inflammatory response and oxidative stress.

The role of interleukin 17 in tumour proliferation, angiogenesis, and metastasis.

With 7.6 million deaths globally, cancer according to the World Health Organisation is still one of the leading causes of death worldwide. Interleukin 17 (IL-17) is a cytokine produced by Th17 cells, a T helper cell subset developed from an activated CD4+ T-cell. Whilst the importance of IL-17 in human autoimmune disease, inflammation, and pathogen defence reactions has already been established, its potential role in cancer progression still needs to be updated. Interestingly studies have demonstrated that IL-17 plays an intricate role in the pathophysiology of cancer, from tumorigenesis, proliferation, angiogenesis, and metastasis, to adapting the tumour in its ability to confer upon itself both immune, and chemotherapy resistance. This review will look into IL-17 and summarise the current information and data on its role in the pathophysiology of cancer as well as its potential application in the overall management of the disease.

Targeted augmented reality-guided transperineal prostate biopsies study: initial experience.

Background: Transperineal biopsy of magnetic resonance imaging (MRI)-detected prostate lesions is now the established technique used in prostate cancer (CaP) diagnostics. Virtual Surgery Intelligence (VSI) Holomedicine by Apoqlar (Hamburg, Germany) is a mixed reality (MR)/augmented reality (AR) software platform that runs on the HoloLens II system (Microsoft, Redford, USA). Multiparametric prostate MRI images were converted into 3D holograms and added into a MR space, enabling visualization of a 3D hologram and image-assisted prostate biopsy. Objective: The Targeted Augmented Reality-GuidEd Transperineal (TARGET) study investigated the feasibility of performing AR-guided prostate biopsies in a MR framework, using the VSI platform in patients with MRI-detected prostate lesions. Methods: Ten patients with a clinical suspicion of CaP on MRI (Prostate Imaging-Reporting and Data System, PI-RADS 4/5) were uploaded to the VSI HoloLens system. Two MR/AR-guided prostate biopsies were then acquired using the PrecisionPoint Freehand transperineal biopsy system. Cognitive fusion biopsies were performed as standard of care following the MR/AR-guided prostate biopsies. Results: All 10 patients successfully underwent MR/AR-guided prostate biopsy after 3D MR images were overlaid on the patient's body. Prostatic tissue was obtained in all MR/AR-guided specimens. Seven patients (70%) had matching histology in both the standard and MR/AR-guided biopsies. The remaining three had ISUP (International Society of Urological Pathology) Grade 2 CaP. There were no immediate complications. Conclusion: We believe this is a world first. The initial feasibility data from the TARGET study demonstrated that an MR/AR-guided prostate biopsy utilizing the VSI Holomedicine system is a viable option in CaP diagnostics. The next stage in development is to combine AR images with real-time needle insertion and to provide further data to formally appraise the sensitivity and specificity of the technique.

Reducing Recurrent Urinary Tract Infections in Women with MV140 Impacts Personal Burden of Disease: Secondary Analyses of a Randomized Placebo-controlled Efficacy Study.

Background: Recurrent urinary tract infection (rUTI) remains a major health burden for women. A randomized, double-blind, placebo-controlled trial (RCT; NCT02543827) reported that female patients with rUTI receiving a sublingual vaccine, MV140, had a reduction in rUTI and increase in UTI-free rate compared with placebo. Objective: To determine the impact of MV140 on the personal burden of disease in women with rUTI using secondary endpoint data from the pivotal RCT evaluating MV140. Design setting and participants: In the primary RCT, female patients with rUTI enrolled in Spain and UK (from October 2015 to April 2019) were randomized to placebo (6 mo) or MV140 (3 or 6 mo), and followed for 12 mo. Individuals analyzed in this secondary analysis included those in the placebo and 3-mo (recommended dose) groups. Intervention: A polybacterial sublingual vaccine, MV140 (four inactivated whole-cell bacteria-Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, and Enterococcus faecalis), or placebo. Outcome measurements and statistical analysis: Symptom severity scoring, antibiotic use, safety, and multiple aspects of quality of life (QoL; Short-Form Questionnaire [SF-36]) were assessed. Results and limitations: Compared with the placebo group (n = 76), the 3-mo vaccinated group (n = 74) experienced fewer overall UTI symptoms (mean symptom score 102.2 ± 222.9 vs 194.2 ± 178.8; p = 0.0002), fewer days on antibiotics (12.4 ± 17.7 vs 28.7 ± 25.2; p = 0.0001), and improved total, general, and physical SF-36 QoL improvement (differences in means for total SF-36 score 15.7; 95% confidence interval [CI] 8.80, 22.64; p < 0.0001), with only social function QoL showing no impact (4.07; 95% CI -4.93, 13.08; p = 0.3744). Conclusions: Three months of MV140 is associated with a reduction of the personal burden of UTI by reducing overall UTI symptoms and antibiotic use, improving QoL in women with rUTI. Patient summary: Three months of MV140 vaccine, which has previously been shown to reduce the risk of urinary tract infection safely, is associated with a reduction in the personal burden of disease.

Isoflurane, a commonly used volatile anesthetic, enhances renal cancer growth and malignant potential via the hypoxia-inducible factor cellular signaling pathway in vitro.

BACKGROUND: Growing evidence indicates that perioperative factors, including choice of anesthetic, affect cancer recurrence after surgery although little is known about the effect of anesthetics on cancer cells themselves. Certain anesthetics are known to affect hypoxia cell signaling mechanisms in healthy cells by up-regulating hypoxia-inducible factors (HIFs). HIFs are also heavily implicated in tumorigenesis and high levels correlate with poor prognosis. METHODS: Renal cell carcinoma (RCC4) cells were exposed to isoflurane for 2 h at various concentrations (0.5-2%). HIF-1α, HIF-2α, phospho-Akt, and vascular endothelial growth factor A levels were measured by immunoblotting at various time points (0-24 h). Cell migration was measured across various components of extracellular matrix, and immunocytochemistry was used to analyze proliferation rate and cytoskeletal changes. RESULTS: Isoflurane up-regulated levels of HIF-1α and HIF-2α and intensified expression of vascular endothelial growth factor A. Exposed cultures contained significantly more cells (1.81 ± 0.25 vs. 1.00 of control; P = 0.03) and actively proliferating cells (89.4 ± 2.80 vs. 64.74 ± 7.09% of control; P = 0.016) than controls. These effects were abrogated when cells were pretreated with the Akt inhibitor, LY294002. Exposed cells also exhibited greater migration on tissue culture-coated (F = 16.89; P = 0.0008), collagen-coated (F = 20.99; P = 0.0003), and fibronectin-coated wells (F = 8.21; P = 0.011) as along with dramatic cytoskeletal rearrangement, with changes to both filamentous actin and α-tubulin. CONCLUSIONS: These results provide evidence that a frequently used anesthetic can exert a protumorigenic effect on a human cancer cell line. This may represent an important contributory factor to high recurrence rates observed after surgery.

A practical guide on the non-antibiotic options available in the prevention of recurrent urinary tract infections in women.

Urinary Tract infection (UTI) is one of the most common infections worldwide, patients present to multiple different specialities in the community, primary and secondary care. Antibiotics are considered standard first line therapy in the treatment of urinary tract infections, however there is an alarming rise in global antibiotic resistance rates, so much so that the World Health Organisation has labelled antibiotic resistance as one of the biggest challenges to public health in our lifetime, publishing a global action plan to tackle this challenge. As a result, there is an increasing need to discover non-antibiotic alternatives, recently a number of novel therapies have been introduced into clinical practice. These are divided into oral, topical, intravesical and immunomodulation therapies. The aim of this paper is to summarise the current non-antibiotic treatments as a practical guide to utilise in patient care.

Sublingual MV140 for Prevention of Recurrent Urinary Tract Infections.

BACKGROUND: Recurrent urinary tract infections (UTIs), which consist of three or more episodes in 1 year or two or more infections in 6 months, affect 5% to 10% of women. MV140, a sublingual preparation of whole-cell inactivated bacteria, has shown clinical benefit in observational studies. This trial examined treatment with MV140 to prevent recurrent UTI. METHODS: In this multicenter, randomized, double-blind, placebo-controlled, parallel-group 1-year trial, 240 women 18 to 75 years of age from Spain and the United Kingdom with recurrent UTI were allocated to receive MV140 for 3 or 6 months or placebo for 6 months in a 1:1:1 ratio. The primary end point was the number of UTIs in the 9-month study period after 3 months of intervention. Key secondary end points were the percentage of women who were UTI free over the above period, time to UTI onset, and health-related quality of life. RESULTS: The median (interquartile range) of UTI episodes was 3.0 (0.5 to 6.0) for placebo compared with 0.0 (0.0 to 1.0) in both groups receiving MV140 (P<0.001). Among women treated with placebo, 25% (95% confidence interval [CI], 15% to 35%) were free of UTIs compared with 56% (95% CI, 44% to 67%) and 58% (95% CI, 44% to 67%) of women who received 3 and 6 months of MV140 treatment, respectively. A total of 205 AEs in 101 participants were registered (81, 76, and 48 in the placebo, 3-month MV140, and 6-month MV140 groups, respectively). CONCLUSIONS: In this controlled trial of modest size and duration, MV140 showed promising clinical efficacy in reducing recurrent UTI in women suffering from this condition. Adverse effects were not clinically limiting. (Funded by Inmunotek S.L. and Syner-Med [Pharmaceutical Products] Ltd.; ClinicalTrials.gov number, NCT02543827.)

Do low dose CT-KUBs really expose patients to more radiation than plain abdominal radiographs?

BACKGROUND: Urolithiasis patients often require frequent urinary tract imaging, leading to high radiation exposure. CT Kidney-Ureter-Bladder (CT-KUB) is the gold standard in urolithiasis detection, however it is thought to harbour significant radiation load. Urologists have therefore utilised abdominal radiographs (XR-KUB) as an alternative, though with markedly lower sensitivity and specificity. We present the first contemporary UK study comparing the effective doses of XR-KUBs with low dose CT-KUBs. METHOD: Fifty-three patients were retrospectively identified in a single centre who underwent both a XR-KUB and a CT-KUB in 2018. Effective-Dose was measured by converting the recorded 'Dose Area/Length Product' via the International Commission on Radiological Protection formula. RESULTS: The average effective dose of XR-KUBs and low dose CT-KUBs were 5.10 mSv and 5.31 mSv respectively. Thirty-four percent (18/53) of patients had a XR-KUBs with a higher effective dose than their low dose CT-KUB. Patients with higher Weight, BMI and AP diameter had higher effective doses for both their XR and low dose CT-KUBs. All patients in our study weighing over 92 kg or with a BMI greater than 32 had a XR-KUBs with a higher effective dose than their low dose CT-KUB. CONCLUSION: This data supports moving away from XR-KUBs for the investigation of urolithiasis, particularly in patients with a high BMI.

Preliminary outcomes of the European multicentre experience with the ZSI 375 artificial urinary sphincter for treatment of stress urinary incontinence in men.

INTRODUCTION: The ZSI 375 is a new artificial urinary sphincter utilised in men suffering from stress urinary incontinence (SUI). We present the first European multicentre study on the effectiveness of ZSI 375. MATERIAL AND METHODS: This study was conducted in a retrospective, non-randomized format in centres across Europe. Between May 2009 and December 2014, ZSI 375 was fitted in 109 SUI patients following radical prostatectomy, transurethral resection of prostate (TURP), rectal surgery and high intensity focused ultrasound (HIFU). Patients with history of pelvic radiotherapy or previous surgical treatment for incontinence or stricture were excluded from the series. Follow-up was completed by December 2016. The key outcome measures included overall improvement and complication rates. RESULTS: A total of 109 patients in 10 European centres were recruited and had the ZSI 375 device implanted. The average patient age was 72 years old. The indication for the majority of patients was incontinence following radical prostatectomy (100/109 patients, 91.74%). On average, patients were incontinent for 48.6 months prior to treatment. All patients used ≥4 pads daily at baseline and thus were classified as suffering from 'severe incontinence'. The average follow-up until the final visit was 43 months. The pad usage decreased to 0.84 on average by the last visit. There were no reported cases of device infection. A total of 9 patients had urethral cuff erosion (8.25%),which was the most common complication in this series. A further 3 men (2.75%) experienced mechanical failure requiring subsequent device reimplantation. The implantation of the ZSI 375 device was considered successful in 92.66% of patients. CONCLUSIONS: The ZSI 375 is an effective surgical treatment option in men with severe stress urinary incontinence.