Ashwin Sachdeva

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Verified

Ashwin verified their affiliation via an institutional email.

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• MBBS, FRCS, PhD
• Clinical Senior Lecturer in Urology & Honorary Consultant Urological Surgeon at The University of Manchester

Advances in multiplex immunofluorescence (mIF) and digital image analysis has enabled simultaneous assessment of protein defects in electron transport chain components. However, current manual methodology is time consuming and labour intensive. Therefore, we developed an automated high-throughput mIF workflow for quantitative single-cell level asse...

Context: Penile cancer is a rare disease but has a significant impact on quality of life. Its incidence is increasing, so it is important to include new and relevant evidence in clinical practice guidelines. Objective: To provide a collaborative guideline that offers worldwide physician and patient guidance for the management of penile cancer....

Background: Abiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation ther...

Context: Lymph node (LN) involvement in penile cancer is associated with poor survival. Early diagnosis and management significantly impact survival, with multimodal treatment approaches often considered in advanced disease. Objective: To assess the clinical effectiveness of treatment options available for the management of inguinal and pelvic l...

Importance Cardiovascular (CV) events remain a substantial cause of mortality among men with advanced and metastatic prostate cancer (PCa). The introduction of novel androgen receptor signaling inhibitors (ARSI) has transformed the treatment landscape of PCa in recent years; however, their associated CV toxic effects remains unclear. Objective To...

One of the major limitations for clinical applications of infrared spectroscopic imaging modalities is the acquisition time required to obtain reasonable images of tissues with high spatial resolution and good...

This randomized clinical trial explores whether hormone intensification at start of androgen deprivation therapy alters selection of androgen receptor ( AR ) gene alterations within the gene body and/or enhancer region.

Objective Germline BRCA2 pathogenic variants (PVs) are known to cause ~4% of prostate cancer, but other homologous repair genes, BRCA1, ATM, PALB2 and Lynch syndrome genes are also involved. Our objective was to assess the contribution of germline and somatic gene variants to prostate cancer. Methods and analysis We reviewed germline/tumour DNA te...

Background: Almost half of all women will have at least one symptomatic urinary tract infection (UTI) in their lifetime. Although usually self-remitting, 74% of women contacting a health professional are prescribed an antibiotic, and in rare instances, they may progress to more severe infections. Therefore, the standard of care for the treatment o...

Androgen-deprivation therapy (ADT) is well established as the standard of care in metastatic prostate cancer (PCa) management; however, ADT has significant adverse effects (AEs) that must be addressed. This review aims to highlight opportunities to mitigate AEs of ADT and explore alternatives in PCa management. Specifically, we discuss behavioral a...

Objective To assess pathological characteristics, clinical features and outcomes of patients diagnosed with peripheral zone (PZ) and transition zone (TZ) prostate cancer after prostatectomy. Methods and analysis We systematically reviewed PubMed, EMBASE and MEDLINE. Primary endpoints were biochemical relapse-free survival (bRFS) and distant metast...

96 Background: Increased body-mass index (BMI) is associated with increased prostate cancer incidence and death. However, an ‘obesity paradox’ exists where patients with BMI have longer survival once diagnosed with cancer. We investigated the influence of BMI on overall survival of veterans with metastatic hormone-sensitive prostate cancer (mHSPC)...

Prostate cancer (PCa) is the second most common male cancer and is attributable to over 375,000 deaths annually. Prostate specific antigen (PSA) is a key biomarker for PCa and therefore, measuring patient PSA levels is an important aspect of the diagnostic pathway. Automated immunoassays are currently utilized for PSA analysis, but they require a l...

Purpose: Up to 90% of men with a positive surgical margin show remaining cancer in subsequent reresections. The risk of local recurrence in men with no penile cancer but the precancerous lesion penile intraepithelial neoplasia at the surgical margin is less well studied and was the aim of this analysis. Material and methods: This was a retrospec...

12 Background: Penile squamous cell carcinoma (PSCC) is rare, representing 0.4-0.6% of all male malignancies in the global-north, as compared with 2-10% in the global-south. Overall survival (OS) dramatically decreases with increased lymph node metastases (LNM). Increased prevalence of pro-tumorigenic M2 CD163+ tumour associated macrophages (TAM) i...

Metastatic and high-risk localized prostate cancer respond to hormone therapy but outcomes vary. Following a pre-specified statistical plan, we used Cox models adjusted for clinical variables to test associations with survival of multi-gene expression-based classifiers from 781 patients randomized to androgen deprivation with or without abiraterone...

Classic Hodgkin lymphoma (cHL) has a rich immune infiltrate, which is an intrinsic component of the neoplastic process. Malignant Hodgkin Reed-Sternberg cells (HRSC) create an immunosuppressive microenvironment by the expression of regulatory molecules, preventing T-cell activation. It has also been demonstrated that mononuclear phagocytes (MNPs) i...

Nephrotoxicity is a major cause of kidney disease and failure in drug development, but understanding of cellular mechanisms is limited, highlighting the need for better experimental models and methodological approaches. Most nephrotoxins damage the proximal tubule (PT), causing functional impairment of solute reabsorption and systemic metabolic com...

Understanding the impact of radiotherapy on the evolution of treatment resistant prostate cancer is critical for selecting effective treatment combinations. Whilst activation of Type 1 interferon signalling is a hallmark of how cells respond to viral infection, in cancer cells, multiple stresses are known to activate this same response. In this stu...

Background The key process of mesenchymal to amoeboid transition (MAT), which enables prostate cancer (PCa) transendothelial migration and subsequent development of metastases in red bone marrow stroma, is driven by phosphorylation of EphA2 S897 by pAkt, which is induced by the omega-6 polyunsaturated fatty acid arachidonic acid. Here we investigat...

Although a lymph node infiltrated by classic Hodgkin lymphoma (cHL) is mostly composed of nonneoplastic immune cells, the malignant Hodgkin Reed-Sternberg cells (HRSC) successfully suppress an anti-tumor immune response, creating a cancer-permissive microenvironment. Accordingly, unleashing the dormant immune cells, for example by checkpoint inhibi...

Classic Hodgkin lymphoma (cHL) has a rich immune infiltrate, which is an intrinsic component of the neoplastic process. Malignant Hodgkin Reed-Sternberg cells (HRSC) create an immunosuppressive microenvironment by the expression of regulatory molecules, preventing T-cell activation. It has also been demonstrated that mononuclear phagocytes (MNP) in...

Here we report the application of a mass spectrometry-based technology, imaging mass cytometry, to perform in-depth proteomic profiling of mitochondrial complexes in single neurons, using metal-conjugated antibodies to label post-mortem human midbrain sections. Mitochondrial dysfunction, particularly deficiency in complex I has previously been asso...

Background Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction. Methods This internati...

Background: Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction. Methods: This internati...

Antimicrobial Resistance Antibiotics have revolutionized modern medicine and agriculture, but it is accepted that their use in veterinary or clinical practice exerts a selective pressure, which accelerates the emergence of antimicrobial resistance (AMR). This cover image illustrates numerous routes via which antibiotics can end up in the environmen...

Objective Coronavirus disease‐19 (COVID‐19) pandemic caused delays in definitive treatment of patients with prostate cancer. Beyond the immediate delay a backlog for future patients is expected. The objective of this work is to develop guidance on criteria for prioritisation of surgery and reconfiguring management pathways for patients with non‐met...

According to a recent report by the World Health Organisation (WHO), antimicrobial resistance (AMR) is considered a global threat comparable to terrorism and climate change. It has been accepted that the use of antibiotics in veterinary or clinical practice exerts a selective pressure, which accelerates the emergence of antimicrobial resistance. Th...

253 Background: Perineural Invasion (PNI) is defined as malignant epithelial cell invasion of the perineural space and nerves. Despite widespread acknowledgement of the clinical significance of PNI as a PCa pathological finding associated with recurrence, increased risk of bone metastasis and poor survival, the molecular mechanism underlying this p...

Background Surgical services are preparing to scale up in areas affected by COVID-19. This study aimed to evaluate the association between preoperative SARS-CoV-2 testing and postoperative pulmonary complications in patients undergoing elective cancer surgery. Methods This international cohort study included adult patients undergoing elective surge...

Patients with high-risk and advanced prostate cancer require safe and efficacious therapies likely to offer a survival advantage while minimizing the treatment-related toxicities. Improvements in the surgical technology, diagnostic modalities, radiological staging, and risk stratification have made surgery for high-risk and advanced prostate cancer...

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) accounts for 0.05-2% of all RCCs. The majority of patients have germline mutations, most frequently in the SDHB gene. People with these mutations are predisposed to developing paragangliomas, phaeochromocytomas and gastrointestinal stromal tumours. Patients should be referred to gen...

Aims: Mitochondrial diseases present with a spectrum of clinical features, usually with multiorgan involvement and are often characterized by a loss of smooth muscle function. Hence, we hypothesized that mitochondrial dysfunction may contribute to lower urinary tract (LUT) dysfunction. Methods: We performed a prospective cohort study at a single...

Context: The role of multiparametric magnetic resonance imaging (mp-MRI) during active surveillance (AS) of prostate cancer needs evaluation. It remains unclear whether mp-MRI can replace prostate biopsies completely during AS. Objective: To evaluate the diagnostic performance of mp-MRI for disease progression in men on AS for prostate cancer....

Background: Hospitalised patients are at increased risk of developing deep vein thrombosis (DVT) in the lower limb and pelvic veins, on a background of prolonged immobilisation associated with their medical or surgical illness. Patients with DVT are at increased risk of developing a pulmonary embolism (PE). The use of graduated compression stockin...

Stem cell (SC) dynamics within the human colorectal crypt SC niche remain poorly understood, with previous studies proposing divergent hypotheses on the predominant mode of SC self-renewal and the rate of SC replacement. Here we use age-related mitochondrial oxidative phosphorylation (OXPHOS) defects to trace clonal lineages within human colorectal...

Stem cell (SC) dynamics within the human colorectal crypt SC niche remain poorly understood, with previous studies proposing divergent hypotheses on the predominant mode of SC self-renewal and the rate of SC replacement. Here we use age-related mitochondrial oxidative phosphorylation (OXPHOS) defects to trace clonal lineages within human colorectal...

Molecularly Imprinted Polymers (MIPs) are synthetic receptors that are able to selectively bind their target molecule and, for this reason, they are currently employed as recognition elements in sensors. In this work, MIP nanoparticles (nanoMIPs) are produced by solid-phase synthesis for a range of templates with different sizes, including a small...

Background Positive surgical margins are a strong prognostic marker of disease outcome following radical prostatectomy, though prior evidence is largely from a PSA-screened population. We therefore aim to evaluate the biochemical recurrence in men with positive surgical margins (PSM) after minimally-invasive radical prostatectomy (MIRP) in a UK ter...

Background: Allogeneic blood transfusion has been associated with immune modulation in other solid organ transplants. Within cardiothoracic surgery, allogeneic blood transfusion is associated with greater postoperative morbidity and mortality. We investigated the impact of allogeneic blood transfusion on rejection, function, and late mortality wit...

Blood transfusion is associated with higher morbidity and mortality after general cardiothoracic surgery but its impact within the transplant population is unclear. We investigated the profile of blood product transfusion in the bilateral lung transplant population and its impact on function and mortality. Three hundred and eleven adult patients wh...

Prostate cancer mortality (PCM) in the USA is among the lowest in the world, whereas PCM in England is among the highest in Europe. This paper aims to assess the association of variation in use of definitive therapy on risk-adjusted PCM in England as compared with the USA. Observational study. Cancer registry data from England and the USA. Men diag...

Background One of the settings where deep vein thrombosis (DVT) in the lower limb and pelvic veins occurs is in hospital with prolonged immobilisation of patients for various surgical and medical illnesses. Using graduated compression stockings (GCS) in these patients has been proposed to decrease the risk of DVT. This is an update of a Cochrane re...

Fourier transform infrared (FT-IR) chemical imaging has been demonstrated as a promising technique to complement histopathological assessment of biomedical tissue samples. Current histopathology practice involves preparing thin tissue sections and staining them using hematoxylin and eosin (H&E;) after which a histopathologist manually assess the ti...

46 Background: Prostate-cancer mortality in the U.S. is amongst the lowest globally. Given historical differences in management between England and the U.S., this paper aims to determine if risk-adjusted prostate-cancer mortality is inferior amongst men in England compared to the U.S. Methods: Patients diagnosed with non-metastatic prostate-cancer...

FTIR chemical imaging has been demonstrated as a promising technique to construct automated systems to complement histopathological evaluation of biomedical tissue samples. The rapid chemical imaging of large areas of tissue has previously been a limiting factor in this application. Consequently, smaller areas of tissue have previously had to be sa...

Low-e microscope slides are a common substrate for biological samples. Typically they are used for transflection infrared microspectroscopy but increasingly they are also being used for micro-ATR experiments since it is assumed that the FTIR-ATR absorbance spectra of cells and tissue on low-e substrates will not contain any spectral contributions f...

Transflection-mode FTIR spectroscopy has become a popular method of measuring spectra from biomedical and other samples due to the relative low cost of substrates compared to transmission windows, and a higher absorbance due to a double pass through the same sample approximately doubling the effective path length. In this publication we state an op...

Transmission and transflection infrared microscopy of biological cells and tissue suffer from significant baseline distortions due to scattering effects, predominantly resonant Mie scattering (RMieS). This scattering can also distort peak shapes and apparent peak positions making interpretation difficult and often unreliable. A correction algorithm...

Balloon atrial septostomy is ordinarily a safe palliative procedure for cyanotic congenital heart disease; however, if echocardiographic guidance is unavailable and fluoroscopy is used, distortions in the cardiac anatomy can invalidate the usual landmarks. Herein, we report iatrogenic mitral papillary muscle rupture during balloon atrial septostomy...

It is hypothesized that cells with stem cell-like properties may be influential in carcinogenesis, possessing the ability to self-renew, produce differentiated daughter cells and resist environmental or therapeutic injury. This has led to a surge in interest in identifying and characterizing the tumour initiating or cancer stem cell (CSC) with the...