Evaluating Cardiac Lead Safety Using Observational, Real-World Data: EP PASSION Proof-of-Concept Study.

BACKGROUND: Traditional post-approval study (PAS) designs have been accepted by regulatory authorities to fulfill post-marketing requirements for cardiac leads but they have several limitations. OBJECTIVES: The authors conducted a proof-of-concept study of alternative methods that utilize real-world data (RWD) to evaluate lead safety in large patient populations. METHODS: Abbott patient device databases were linked with Medicare Fee-For-Service (FFS) claims to identify lead complications among patients implanted with Abbott Optisure™ lead. A 1:1 comparison between the PAS method and RWD method of detecting mechanical lead-related complication events was conducted in 444 PAS subjects who were enrolled in Medicare FFS. Agreement between methods was evaluated using McNemar's test and Cohen's kappa. Survival free from complications at 3 years was compared between the PAS and RWD cohorts using an equivalence acceptance criterion of ±2.5%. RESULTS: There were 1,171 PAS patients and 5,804 Medicare FFS patients who received an Optisure™ lead between August 27, 2014 - June 14, 2016. Patients were followed through December 31, 2018. Complete agreement was found between PAS-reported and claims-detected complications (McNemar's p-value=1.00, Cohen's Kappa = 1.0). Survival free from complications at 3 years using the RWD method was 98.4% (95% CL: 98.0%-98.7%), which was within the acceptable range of the PAS 98.4% (95% CL: 97.6%-99.0%). CONCLUSION: These results show a close agreement between RWD-detected and PAS-reported lead complication rates, which highlight the potential benefits of RWD-based methods to enhance the generation of clinical evidence for lead safety.

Mortality Benefit Among Primary Prevention Implantable Cardioverter-Defibrillator Recipients on Contemporary Heart Failure Treatment.

BACKGROUND: Past clinical trials have shown the benefit of implantable cardioverter-defibrillators (ICDs) for reducing sudden cardiac death in at-risk patients. However, heart failure management and ICD technology have changed since these trials were first published. An updated assessment of ICD mortality benefit is needed. OBJECTIVES: The purpose of this study was to compare mortality rates between patients with a primary prevention (PP) indication for an ICD who did or did not receive an ICD using a contemporary, real-world data set. METHODS: Data was obtained from a large electronic health record data set covering patients in the United States from 2012 through 2020 who had a PP indication for an ICD and survived at least 1-year postindication. RESULTS: A total of 25,296 patients were identified as having a PP indication for ICD implantation, of which 2,118 (8.4%) were treated with an ICD within a year. Treated patients were younger than nontreated patients (age 63.4 years vs 66.1 years) with a smaller proportion of women (25.0% vs 36.7%). After 4-to-1 propensity matching, treated patients had similar clinical characteristics to nontreated patients. A Cox proportional hazard model estimated a 24.3% lower risk of all-cause mortality in patients when treated vs not treated with an ICD (HR: 0.757; 95% CI: 0.678-0.835; P <0.001). There was no detectable difference in ICD benefit between patients with ischemic and nonischemic heart disease (P = 0.50). CONCLUSIONS: ICD treatment of patients with a PP indication is associated with improved mortality even in the context of evolving adjunctive HF treatment, consistent with earlier landmark trials.

Clinical Trials and Therapeutic Approaches for Healthcare Challenges in Pakistan.

Pakistan faces tremendous challenges in providing healthcare due to a lack of consistent policymaking, increasing expenditure and exponential growth in population since its inception in 1947. These challenges are not just driven by politics, policy and allocation of resources but also by healthcare, environment and characteristics of the population biology. Clinical trials provide the best way to find population-specific, cost-effective treatments that do not merely mimic those used in wealthier nations. This article analyzes all clinical studies conducted with at least one site in Pakistan listed on ClinicalTrials.gov, combined with a short overview that considers new therapeutic approaches that can be investigated in future clinical trials. Therapies using repurposed medicines are of particular interest as they use affordable drugs that are already widely available.

Persistent and Recurrent Device-Related Thrombus After Left Atrial Appendage Closure: Incidence, Predictors, and Outcomes.

BACKGROUND: Scarce data exist on the evolution of device-related thrombus (DRT) after left atrial appendage closure (LAAC). OBJECTIVES: This study sought to assess the incidence, predictors, and clinical impact of persistent and recurrent DRT in LAAC recipients. METHODS: Data were obtained from an international multicenter registry including 237 patients diagnosed with DRT after LAAC. Of these, 214 patients with a subsequent imaging examination after the initial diagnosis of DRT were included. Unfavorable evolution of DRT was defined as either persisting or recurrent DRT. RESULTS: DRT resolved in 153 (71.5%) cases and persisted in 61 (28.5%) cases. Larger DRT size (OR per 1-mm increase: 1.08; 95% CI: 1.02-1.15; P = 0.009) and female (OR: 2.44; 95% CI: 1.12-5.26; P = 0.02) were independently associated with persistent DRT. After DRT resolution, 82 (53.6%) of 153 patients had repeated device imaging, with 14 (17.1%) cases diagnosed with recurrent DRT. Overall, 75 (35.0%) patients had unfavorable evolution of DRT, and the sole predictor was average thrombus size at initial diagnosis (OR per 1-mm increase: 1.09; 95% CI: 1.03-1.16; P = 0.003), with an optimal cutoff size of 7 mm (OR: 2.51; 95% CI: 1.39-4.52; P = 0.002). Unfavorable evolution of DRT was associated with a higher rate of thromboembolic events compared with resolved DRT (26.7% vs 15.1%; HR: 2.13; 95% CI: 1.15-3.94; P = 0.02). CONCLUSIONS: About one-third of DRT events had an unfavorable evolution (either persisting or recurring), with a larger initial thrombus size (particularly >7 mm) portending an increased risk. Unfavorable evolution of DRT was associated with a 2-fold higher risk of thromboembolic events compared with resolved DRT.

Upcycling of surgical facemasks into carbon based thin film electrode for supercapacitor technology.

Polypropylene (PP), a commonly used plastic, is used for making the outer layers of a surgical face mask. In 2020, around 3 billion surgical face masks were disposed into the environment, causing a huge threat to wildlife, aquatic life, and ecosystems. In this work, we have reported the sulfonation technique for stabilizing the surgical face masks and their conversion into carbon nanoparticles for application as a supercapacitor electrode. The electrode is fabricated by preparing a slurry paste of carbon nanoparticles and pasting it on a conductive wearable fabric. To investigate the performance of the carbon thin film electrode, electrochemical techniques are employed. The Cyclic Voltammetry (CV) analysis performed at different scan rates in a 6 molar KOH electrolyte reveals that the carbon thin film acts as a positive electrode. At 4 A g-1, the electrode shows a specific capacitance of 366.22 F g-1 and 100% retention of specific capacitance for 8000 cycles. A two-electrode asymmetric device is fabricated using carbon thin film as the positive electrode, NiO thin film as the negative electrode, and a KOH separator between two electrodes. The device shows a specific capacitance of 113.73 F g-1 at 1.3 A g-1 and glows a red LED for 6 min. This work is a step towards upcycling the waste produced from surgical face masks used during the COVID-19 pandemic and its application for energy storage.

Laser-Based Door Localization for Autonomous Mobile Service Robots.

For autonomous mobile service robots, closed doors that are in their way are restricting obstacles. In order to open doors with on-board manipulation skills, a robot needs to be able to localize the door's key features, such as the hinge and handle, as well as the current opening angle. While there are vision-based approaches for detecting doors and handles in images, we concentrate on analyzing 2D laser range scans. This requires less computational effort, and laser-scan sensors are available on most mobile robot platforms. Therefore, we developed three different machine learning approaches and a heuristic method based on line fitting able to extract the required position data. The algorithms are compared with respect to localization accuracy with help of a dataset containing laser range scans of doors. Our LaserDoors dataset is publicly available for academic use. Pros and cons of the individual methods are discussed; basically, the machine learning methods could outperform the heuristic method, but require special training data when applied in a real application.

Opposite changes in the expression of clathrin and caveolin-1 in normal and cancerous human prostate tissue: putative clathrin-mediated recycling of EGFR.

Endocytosis, an important macromolecule uptake process in cells, is known to be dysregulated in cancer. Clathrin and caveolin-1 proteins play a major role in receptor-mediated endocytosis. We have used a quantitative, unbiased and semi-automated method to measure in situ protein expression of clathrin and caveolin-1 in cancerous and paired normal (cancer adjacent, non-cancerous) human prostate tissue. There was a significant (p < 0.0001) increase in the expression of clathrin in prostate cancer samples (N = 29, n = 91) compared to normal tissue (N = 29, n = 67) (N = number of patients, n = number of cores in tissue arrays). Conversely, there was a significant (p < 0.0001) decrease in expression of caveolin-1 in prostate cancer tissue compared to normal prostate tissue. The opposite change in expression of the two proteins was highly correlated to increasing cancer aggressiveness. There was also a concurrent increase in the expression of epidermal growth factor receptor (EGFR), a key receptor in carcinogenesis, with clathrin in prostate cancer tissue, indicating recycling of EGFR through clathrin-mediated endocytosis (CME). These results indicate that in prostate cancer, caveolin-1-mediated endocytosis (CavME) may be acting as a brake and increase in CME may facilitate tumorigenicity and aggressiveness of prostate cancer through recycling of EGFR. Changes in the expression of these proteins can also potentially be used as a biomarker for prostate cancer to aid in diagnosis and prognosis and clinical decision-making.

Graphene and Its Derivatives: Synthesis and Application in the Electrochemical Detection of Analytes in Sweat.

Wearable sensors and invasive devices have been studied extensively in recent years as the demand for real-time human healthcare applications and seamless human-machine interaction has risen exponentially. An explosion in sensor research throughout the globe has been ignited by the unique features such as thermal, electrical, and mechanical properties of graphene. This includes wearable sensors and implants, which can detect a wide range of data, including body temperature, pulse oxygenation, blood pressure, glucose, and the other analytes present in sweat. Graphene-based sensors for real-time human health monitoring are also being developed. This review is a comprehensive discussion about the properties of graphene, routes to its synthesis, derivatives of graphene, etc. Moreover, the basic features of a biosensor along with the chemistry of sweat are also discussed in detail. The review mainly focusses on the graphene and its derivative-based wearable sensors for the detection of analytes in sweat. Graphene-based sensors for health monitoring will be examined and explained in this study as an overview of the most current innovations in sensor designs, sensing processes, technological advancements, sensor system components, and potential hurdles. The future holds great opportunities for the development of efficient and advanced graphene-based sensors for the detection of analytes in sweat.

UV-vis spectroscopic method for detection and removal of heavy metal ions in water using Ag doped ZnO nanoparticles.

The primary source of heavy metal discharge into the water is human activity and urbanization near water bodies. Contamination of drinking water sources with heavy metals has a harmful impact on the environment and human health. The most commonly used heavy metals are Zinc (Zn), Copper (Cu), Nickel (Ni), Lead (Pb), Cadmium (Cd), Chromium (Cr), Arsenic (As), Mercury (Hg), etc. The heavy metal ions are easily absorbed by living things via water and spread throughout the food chain, posing a threat to humans, plants, and animals (Zhang et al., 2018; Lu et al., 2019; Ma et al., 2020; Gao et al., 2018; Wen et al., 2018; Saranya et al., 2021). Colorimetric sensing is a simple and cost-effective method for the detection of heavy metal ions. Moreover, the results can be analysed with naked eye. In this work, Ag doped ZnO nanoparticles synthesized via co-precipitation method are used for the colorimetric detection of heavy metal ions. The nanoparticles are characterized for their morphology, structural, and chemical analysis using XRD, SEM, EDS, and XPS techniques. The synthesized nanoparticles are used for the colorimetric detection of heavy metal ions. The heavy metal ions such as Ni2+, Cu2+, Cr3+, Cr6+, Fe2+, and Fe3+ are successfully detected and the color change is visible from the naked eye. The minimum concentration detected is found to be 100 µM. The results are analysed via UV-vis spectroscopy. In addition to detection, the nanoparticles are further used as catalyst during the degradation of above detected heavy metal ions using NaBH4. All the heavy metal ions are degraded with in the duration of 30 min. Thus, the Ag doped ZnO nanoparticles successfully detected the heavy metal ions in aqueous solution and also acted as a catalyst during their degradation.

Pediatric Sports Injuries.

Recreational sports are more popular, with many athletes involved year-round in multiple sports and on multiple teams. Most athletes do not take proper rest, making them more susceptible to stress-related injuries. There are numerous sports-related injuries in the foot and ankle. These issues can be non-traumatic, due to chronic repetitive stresses, or traumatic. Most of these injuries are managed conservatively, and athletes do well and return to play, while some do better with operative management. This article discusses a few of the sports injuries that are common in the leg, foot, and ankle and the recovery process.

Recent Advances in Electrochemical Biosensors: Applications, Challenges, and Future Scope.

The electrochemical biosensors are a class of biosensors which convert biological information such as analyte concentration that is a biological recognition element (biochemical receptor) into current or voltage. Electrochemical biosensors depict propitious diagnostic technology which can detect biomarkers in body fluids such as sweat, blood, feces, or urine. Combinations of suitable immobilization techniques with effective transducers give rise to an efficient biosensor. They have been employed in the food industry, medical sciences, defense, studying plant biology, etc. While sensing complex structures and entities, a large data is obtained, and it becomes difficult to manually interpret all the data. Machine learning helps in interpreting large sensing data. In the case of biosensors, the presence of impurity affects the performance of the sensor and machine learning helps in removing signals obtained from the contaminants to obtain a high sensitivity. In this review, we discuss different types of biosensors along with their applications and the benefits of machine learning. This is followed by a discussion on the challenges, missing gaps in the knowledge, and solutions in the field of electrochemical biosensors. This review aims to serve as a valuable resource for scientists and engineers entering the interdisciplinary field of electrochemical biosensors. Furthermore, this review provides insight into the type of electrochemical biosensors, their applications, the importance of machine learning (ML) in biosensing, and challenges and future outlook.

Contractile and Structural Properties of Detrusor from Children with Neurogenic Lower Urinary Tract Dysfunction.

Neurogenic lower urinary tract (NLUT) dysfunction in paediatric patients can arise after congenital or acquired conditions that affect bladder innervation. With some patients, urinary tract dysfunction remains and is more difficult to treat without understanding the pathophysiology. We measured in vitro detrusor smooth muscle function of samples from such bladders and any association with altered Wnt-signalling pathways that contribute to both foetal development and connective tissue deposition. A comparator group was tissue from children with normally functioning bladders. Nerve-mediated and agonist-induced contractile responses and passive stiffness were measured. Histology measured smooth muscle and connective tissue proportions, and multiplex immunohistochemistry recorded expression of protein targets associated with Wnt-signalling pathways. Detrusor from the NLUT group had reduced contractility and greater stiffness, associated with increased connective tissue content. Immunohistochemistry showed no major changes to Wnt-signalling components except down-regulation of c-Myc, a multifunctional regulator of gene transcription. NLUT is a diverse term for several diagnoses that disrupt bladder innervation. While we cannot speculate about the reasons for these pathophysiological changes, their recognition should guide research to understand their ultimate causes and develop strategies to attenuate and even reverse them. The role of changes to the Wnt-signalling pathways was minor.

Associations between sinus tachycardia and adverse cardiovascular outcomes and mortality in cancer patients.

BACKGROUND: Sinus tachycardia in cancer reflects a significant multi-system organ stressor and disease, with sparse literature describing its clinical significance. We assessed cardiovascular (CV) and mortality prognostic implications of sinus tachycardia in cancer patients. METHODS: We conducted a case-control study of 622 cancer patients at a U.S. urban medical center from 2008 to 2016. Cases had ECG-confirmed sinus tachycardia [heart rate (HR) ≥100 bpm] in ≥3 different clinic visits within 1 year of cancer diagnosis excluding a history of pulmonary embolism, thyroid dysfunction, left ventricular ejection fraction <50%, atrial fibrillation/flutter, HR >180 bpm. Adverse CV outcomes (ACVO) were heart failure with preserved ejection fraction (HFpEF), HF with reduced EF (HFrEF), hospital admissions for HF exacerbation (AHFE), acute coronary syndrome (ACS). Regression analyses were conducted to examine the effect of sinus tachycardia on overall ACVO and survival. RESULTS: There were 51 cases, age and sex-matched with 571 controls (mean age 70±10, 60.5% women, 76.4% Caucasian). In multivariate analysis over a 10-year follow-up period, sinus tachycardia (HR ≥100 vs. <100 bpm) was an independent predictor of overall ACVO (OR 2.8, 95% CI: 1.4-5.5; P=0.006). There was increased incidence of HFrEF (OR 3.3, 95% CI: 1.6-6.5; P=0.004) and AHFE (OR 6.3, 95% CI: 1.6-28; P=0.023), but not HFpEF or ACS (P>0.05) compared with controls. Sinus tachycardia was a significant predictor of overall mortality after adjusting for significant covariates (HR 2.9, 95% CI 1.8-5; P<0.001). CONCLUSIONS: Independent of typical factors that affect cardiovascular disease, sinus tachycardia around the time of cancer treatment is associated with increased ACVO and mortality in cancer patients at 10 years of follow-up.

Predictors of Device-Related Thrombus Following Percutaneous Left Atrial Appendage Occlusion.

BACKGROUND: Device-related thrombus (DRT) has been considered an Achilles' heel of left atrial appendage occlusion (LAAO). However, data on DRT prediction remain limited. OBJECTIVES: This study constructed a DRT registry via a multicenter collaboration aimed to assess outcomes and predictors of DRT. METHODS: Thirty-seven international centers contributed LAAO cases with and without DRT (device-matched and temporally related to the DRT cases). This study described the management patterns and mid-term outcomes of DRT and assessed patient and procedural predictors of DRT. RESULTS: A total of 711 patients (237 with and 474 without DRT) were included. Follow-up duration was similar in the DRT and no-DRT groups, median 1.8 years (interquartile range: 0.9-3.0 years) versus 1.6 years (interquartile range: 1.0-2.9 years), respectively (P = 0.76). DRTs were detected between days 0 to 45, 45 to 180, 180 to 365, and >365 in 24.9%, 38.8%, 16.0%, and 20.3% of patients. DRT presence was associated with a higher risk of the composite endpoint of death, ischemic stroke, or systemic embolization (HR: 2.37; 95% CI, 1.58-3.56; P < 0.001) driven by ischemic stroke (HR: 3.49; 95% CI: 1.35-9.00; P = 0.01). At last known follow-up, 25.3% of patients had DRT. Discharge medications after LAAO did not have an impact on DRT. Multivariable analysis identified 5 DRT risk factors: hypercoagulability disorder (odds ratio [OR]: 17.50; 95% CI: 3.39-90.45), pericardial effusion (OR: 13.45; 95% CI: 1.46-123.52), renal insufficiency (OR: 4.02; 95% CI: 1.22-13.25), implantation depth >10 mm from the pulmonary vein limbus (OR: 2.41; 95% CI: 1.57-3.69), and non-paroxysmal atrial fibrillation (OR: 1.90; 95% CI: 1.22-2.97). Following conversion to risk factor points, patients with ≥2 risk points for DRT had a 2.1-fold increased risk of DRT compared with those without any risk factors. CONCLUSIONS: DRT after LAAO is associated with ischemic events. Patient- and procedure-specific factors are associated with the risk of DRT and may aid in risk stratification of patients referred for LAAO.

QuArray: an application for tissue array whole slide image export and signal analysis.

MOTIVATION: Tissue array (TA) staining, combined with whole slide imaging (WSI) methods facilitate discovery of biomarkers for diagnosis, prognostication and disease stratification. A key impediment in TA WSI analysis is handling missing tissue and artefacts when identifying tissue cores before quantitative, standardized downstream analysis. There is a need for an open access, user friendly, integrated analysis of the WSI generated using TAs in clinical and scientific research laboratories. RESULTS: We have developed QuArray (Quantitative Array Application) for image export and signal analysis of TAs using WSI. The application input is a WSI and a corresponding TA configuration file. QuArray identifies and exports core images and analyses chromogen staining in a simple graphical user interface. Output data is saved to file for further analysis including indexed data. AVAILABILITYAND IMPLEMENTATION: Available for download from https://github.com/c-arthurs/QuArray under an MIT licence. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Prevention and Management of Supine Hypertension in Patients With Orthostatic Hypotension.

BACKGROUND: Orthostatic hypotension (OH) is a potentially debilitating condition caused by dysfunction of the autonomic nervous system, which is essential for the physiologic response to orthostatic posture. In addition to OH, autonomic dysfunction may also be associated with the development of concurrent supine hypertension (SH). AREAS OF UNCERTAINTY: This paradoxical effect speaks to the complexity of the pathogenesis of autonomic disease and greatly complicates management of these patients. Clinicians are faced with a dilemma because aggressive treatment of orthostatic intolerance can worsen supine hypertension and attempts to control supine hypertension can worsen orthostatic intolerance. DATA SOURCES: Systematic review of the published literature. PREVENTION OF SUPINE HYPERTENSION: Patients should aim to avoid known stressors, perform physical maneuvers (eg, slowly getting up from bed, sleeping with head of bed elevated), manage underlying related conditions (eg, diabetes mellitus), and exercise. MANAGEMENT OF SUPINE HYPERTENSION: With failure of conservative management, patients may advance to pharmacologic therapy. It is important to understand the underlying suspected etiology of the syndrome of supine hypertension and OH (SH-OH) to select promising pharmacologic agents. This article reviews medical treatment options to work toward achieving a better quality of life for patients afflicted with this disease. Although clonidine and beta-blockers can be used to treat hypertension without causing significant hypotension, midodrine, pyridostigmine, and droxidopa may be helpful in preventing OH. CONCLUSION: The etiology and severity of autonomic dysfunction vary widely between patients, suggesting a need for an individualized treatment approach. Achieving perfect blood pressure control is not a realistic goal. Rather, treatment should be aimed at improving the patient's quality of life and decreasing their risk of injury and organ damage.

Contractile function of detrusor smooth muscle from children with posterior urethral valves - The role of fibrosis.

INTRODUCTION: Posterior urethral valves (PUV) is the most common cause of congenital bladder outflow obstruction with persistent lower urinary tract and renal morbidities. There is a spectrum of functional bladder disorders ranging from hypertonia to bladder underactivity, but the aetiology of these clinical conditions remains unclear. AIMS AND OBJECTIVES: We tested the hypothesis that replacement of detrusor muscle with non-muscle cells and excessive deposition of connective tissue is an important factor in bladder dysfunction with PUV. We used isolated detrusor samples from children with PUV and undergoing primary or secondary procedures in comparison to age-matched data from children with functionally normal bladders. In vitro contractile properties, as well as passive stiffness, were measured and matched to histological assessment of muscle and connective tissue. We examined if a major pathway for fibrosis was altered in PUV tissue samples. METHODS: Isometric contractions were measured in vitro in response to either stimulation of motor nerves to detrusor or exposure to cholinergic and purinergic receptor agonists. Passive mechanical stiffness was measured by rapid stretching of the tissue and recording changes to muscle tension. Histology measured the relative amounts of detrusor muscle and connective tissue. Multiplex quantitative immunofluorescence labelling using five epitope markers was designed to determine cellular pathways, in particular the Wnt-signalling pathway, responsible for any changes to excessive deposition of connective tissue. RESULTS AND DISCUSSION: PUV tissue showed equally reduced contractile function to efferent nerve stimulation or exposure to contractile agonists. Passive muscle stiffness was increased in PUV tissue samples. The smooth muscle:connective tissue ratio was also diminished and mirrored the reduction of contractile function and the increase of passive stiffness. Immunofluorescence labelling showed in PUV samples increased expression of the matrix metalloproteinase, MMP-7; as well as cyclin-D1 expression suggesting cellular remodelling. However, elements of a fibrosis pathway associated with Wnt-signalling were either reduced (ß-catenin) or unchanged (c-Myc). The accumulation of extracellular matrix, containing collagen, will contribute to the reduced contractile performance of the bladder wall. It will also increase tissue stiffness that in vivo would lead to reduced filling compliance. CONCLUSIONS: Replacement of smooth muscle with fibrosis is a major contributory factor in contractile dysfunction in the hypertonic PUV bladder. This suggests that a potential strategy to restore normal contractile and filling properties is development of the effective use of antifibrotic agents.

Equine penile squamous cell carcinoma: expression of biomarker proteins and EcPV2.

Equine penile squamous cell carcinoma (EpSCC) is a relatively common cutaneous neoplasm with a poor prognosis. In this study, we aimed to determine the protein expression and colocalisation of FRA1, c-Myc, Cyclin D1, and MMP7 in normal (NT), tumour (T), hyperplastic epidermis and/or squamous papilloma (Hyp/Pap), poorly-differentiated (PDSCC), or well-differentiated (WDSCC) EpSCC using a tissue array approach. Further objectives were to correlate protein expression to (i) levels of inflammation, using a convolutional neural network (ii) equine papillomavirus 2 (EcPV2) infection, detected using PCR amplification. We found an increase in expression of FRA1 in EpSCC compared to NT samples. c-Myc expression was higher in Hyp/Pap and WDSCC but not PDSCC whereas MMP7 was reduced in WDSCC compared with NT. There was a significant increase in the global intersection coefficient (GIC) of FRA1 with MMP7, c-Myc, and Cyclin D1 in EpSCC. Conversely, GIC for MMP7 with c-Myc was reduced in EpSCC tissue. Inflammation was positively associated with EcPV2 infection in both NT and EpSCC but not Hyp/Pap. Changes in protein expression could be correlated with EcPV2 for Cyclin D1 and c-Myc. Our results evaluate novel biomarkers of EpSCC and a putative correlation between the expression of biomarkers, EcPV2 infection and inflammation.

The genetic landscapes of urological cancers and their clinical implications in the era of high-throughput genome analysis.

OBJECTIVE: With the advent of high-throughput genome analysis, we are increasingly able to sequence and hence understand the pathogenic processes underlying individual cancers. Recently, consortiums such as The Cancer Genome Atlas (TCGA) have performed large-scale projects to this end, providing significant amounts of information regarding the genetic landscapes of several cancers. PATIENTS AND METHODS: We performed a narrative review of studies from the TCGA and other major studies. We aimed to summarise data exploring the clinical implications of specific genetic alterations, both prognostically and therapeutically, in four major urological cancers. These were renal cell carcinoma, muscle-invasive bladder cancer/carcinoma, prostate cancer, and testicular germ cell tumours. RESULTS: With these four urological cancers, great strides have been made in the molecular characterisation of tumours. In particular, recent studies have focussed on identifying molecular subtypes of tumours with characteristic genetic alterations and differing prognoses. Other prognostic alterations have also recently been identified, including those pertaining to epigenetics and microRNAs. In regard to treatment, numerous options are emerging for patients with these cancers such as including immune checkpoint inhibition, epigenetic-based treatments, and agents targeting MAPK, PI3K, and DNA repair pathways. There are a multitude of trials underway investigating the effects of these novel agents, the results of which are eagerly awaited. CONCLUSIONS: As medicine chases the era of personalised care, it is becoming increasingly important to provide individualised prognoses for patients. Understanding how specific genetic alterations affects prognosis is key for this. It will also be crucial to provide highly targeted treatments against the specific genetics of a patient's tumour. With work performed by the TCGA and other large consortiums, these aims are gradually being achieved. Our review provides a succinct overview of this exciting field that may underpin personalised medicine in urological oncology.