Publications
511 results found
Khullar V, Lemmon B, Acar O, et al., 2024, Does COVID-19 cause or worsen LUT dysfunction, what are the mechanisms and possible treatments? ICI-RS 2023., Neurourol Urodyn
INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and produced a worldwide pandemic in 2020. There have been 770,875,433 confirmed cases and 6,959,316 attributed deaths worldwide until September 19, 2023. The virus can also affect the lower urinary tract (LUT) leading to bladder inflammation and producing lower urinary tract symptoms (LUTS) in both the acute and chronic phases of disease. METHODS: At the 2023 meeting of the International Consultation on Incontinence-Research Society (ICI-RS), the literature relating to COVID-19 and bladder dysfunction was reviewed. The LUTS reported, as well as the pathophysiology of these bladder symptoms, were the subject of considerable discussion. A number of different topics were discussed including lower LUTS reported in COVID-19, how SARS-CoV-2 may infect and affect the urinary tract, and proposed mechanisms for how viral infection result in new, worsened, and in some persisting LUTS. CONCLUSIONS: The workshop discussed the interaction between the virus and the immune system, covering current evidence supporting theories underlying the causes of acute and chronic LUTS related to COVID-19 infection. Research questions for further investigation were suggested and identified.
Sarker P, Pereira GMV, Khullar V, et al., 2024, VDR, CXCR1, CXCR2, PSCA Polymorphisms and Recurrent Urinary Tract Infections in Women: Genetic Association Study., Int Urogynecol J
INTRODUCTION AND HYPOTHESIS: Urinary tract infection (UTI) is one of the most common human infections. Evidence suggests that there might be a genetic predisposition to UTI. Previous small candidate gene studies have suggested that common variants in genes involved in the immune response to UTI could increase susceptibility to the development of recurrent UTI (rUTI). The objective was to conduct a gene association study to replicate previous gene association studies identifying single nucleotide polymorphisms (SNPs) putatively associated with rUTI in adult women. METHODS: Women with a history of rUTI and healthy controls were recruited (n = 1,008) from gynaecology outpatient clinics. Participants completed a signed consent form and questionnaire for phenotyping. DNA was extracted from blood or saliva samples for each participant. Putative associated SNPs were identified from a comprehensive systematic review of prior gene association studies. Primers for each selected SNP were designed, and genotyping was conducted using a competitive polymerase chain reaction (PCR) method. The Chi-squared test was used to assess the association between each variant and rUTI. Genotyping quality was assessed by checking for deviation from Hardy-Weinberg equilibrium. RESULTS: We found no association between SNPs tested in the VDR (p = 0.16, p = 0.09, p = 0.36), CXCR1 (p = 0.09), CXCR2 (p = 0.39), PSCA (p = 0.74) genes, and rUTI in adult women. CONCLUSIONS: To our knowledge, this is the largest study to date, finding no significant associations. Previously reported positive associations may have been due to type 1 error, or genotyping errors. Future studies should adjust for confounders and employ adequate sample sizes. A greater understanding of the genetic components associated with rUTI may influence future treatment guidelines and screening for susceptible patients.
Yu J, Varella Pereira GM, Allen-Brady K, et al., 2023, Genetic polymorphisms associated with urinary tract infection in children and adults: a systematic review and meta-analysis., Am J Obstet Gynecol
INTRODUCTION: The lifetime risk of urinary tract infection is known from first-degree relative studies to be highly heritable. Associations have also been observed across the life course from pediatric urinary tract infection to recurrent urinary tract infection in adulthood, suggesting lifelong susceptibility factors. Candidate gene studies and genome-wide association studies have tested for genetic associations of urinary tract infection; however, no contemporary systematic synthesis of studies is available. OBJECTIVE: We conducted a systematic review to identify all genetic polymorphisms tested for an association with urinary tract infection in children and adults; and to assess their strength, consistency, and risk of bias among reported associations. DATA SOURCES AND STUDY ELIGIBILITY CRITERIA: PubMed, HuGE Navigator and Embase were searched from January 1, 2005 to November 16, 2023, using a combination of genetic and phenotype key words. STUDY APPRAISAL AND SYNTHESIS METHODS: Fixed and random effects meta-analyses were conducted using codominant models of inheritance in metan. The interim Venice criteria were used to assess their credibility of pooled associations. RESULTS: After removing 451 duplicates, 1821 studies reports were screened, with 106 selected for full-text review, 22 were included in the meta-analysis (7 adult studies and 15 pediatric studies). Our meta-analyses demonstrated significant pooled associations for pediatric urinary tract infection with variation in CXCR1, IL8, TGF, TLR4 and VDR; all of which have plausible roles in the pathogenesis of urinary tract infection. Our meta-analyses also demonstrated a significant pooled association for adult urinary tract infection with variation in CXCR1. All significant pooled associations were graded according to their epidemiological credibility, sample sizes, heterogeneity between studies, and risk of bias. CONCLUSION: This systematic review provides a current synthesis of the known genetic architec
Bhide AA, Lemmon B, Rahmanou P, et al., 2023, Bladder contractility index changes with short-term antimuscarinic therapy in patients with detrusor overactivity: A placebo controlled randomised study, Continence, Vol: 8
Aims: Bladder contractility is altered by high doses of anticholinergics. It is unknown if anticholinergics at doses used for treating overactive bladder alter bladder contractility. This is a randomised, double-blind, placebo controlled cross-over multicentre study with two 2-week treatment periods. Patients with a previous diagnosis of detrusor overactivity and reporting urinary frequency of at least seven times a day, one or more episodes of urge urinary incontinence per week and at least seven episodes of urgency per week were included. Methods: After a two-week washout period, subjects were randomised to receive propiverine 20 mg od, propiverine 15 mg tds, oxybutynin 5 mg tds or placebo for 2 weeks. After a second washout period, they were randomised to receive 2 weeks of another treatment not previously used. Ambulatory urodynamic monitoring was performed according to ICS standards for 4 h, using a standardised protocol before and after treatment. The bladder contractility index (BCI) was given by the formula: BCI = PdetQmax+ 5Qmax. The main outcome measure was the average BCI for the first 2 voids for each of the treatment. Results: 77 participants were recruited. The average BCI for the first two voids was 143 (range 24–314). The BCI was not statistically different before and after antimuscarinic therapy or placebo although there were reductions in urinary frequency and urgency over placebo indicating efficacy over placebo in the treatment of detrusor overactivity. Conclusions: The bladder contractility index did not change significantly in response to antimuscarinic therapy despite a therapeutic effect. This suggests efficacy is mediated by an effect on another system such as sensory rather than motor function.
Wyndaele M, Charrua A, Hervé F, et al., 2023, Beyond the urothelium: Interplay between autonomic nervous system and bladder inflammation in urinary tract infection, bladder pain syndrome with interstitial cystitis and neurogenic lower urinary tract dysfunction in spinal cord injury-ICI-RS 2023., Neurourol Urodyn
INTRODUCTION: Inflammation and neuronal hypersensitivity are reactive protective mechanisms after urothelial injury. In lower urinary tract dysfunctions (LUTD), such as urinary tract infection (UTI), bladder pain syndrome with interstitial cystitis (BPS/IC) and neurogenic LUTD after spinal cord injury (SCI), chronic inflammation can develop. It is unclear how the protective reactionary inflammation escalates into chronic disease in some patients. METHODS: During its 2023 meeting in Bristol, the International Consultation on Incontinence-Research Society (ICI-RS) reviewed the urothelial and inflammatory changes after UTI, BPS/IC and SCI. Potential factors contributing to the evolution into chronic disease were explored in a think-tank. RESULTS: Five topics were discussed. (1) Visceral fat metabolism participates in the systemic pro-inflammatory effect of noradrenalin in BPS/IC and SCI. Sympathetic nervous system-adipocyte-bladder crosstalk needs further investigation. (2) Sympathetic hyperactivity also potentiates immune depression in SCI and needs to be investigated in BPS/IC. Gabapentin and tumor necrosis factor-α are promising research targets. (3) The exact peripheral neurons involved in the integrative protective unit formed by nervous and immune systems need to be further identified. (4) Neurotransmitter changes in SCI and BPS/IC: Neurotransmitter crosstalk needs to be considered in identifying new therapeutic targets. (5) The change from eubiosis to dysbiosis in SCI can contribute to UTI susceptibility and needs to be unraveled. CONCLUSIONS: The think-tank discussed whether visceral fat metabolism, immune depression through sympathetic hyperactivity, peripheral nerves and neurotransmitter crosstalk, and the change in microbiome could provide explanations in the heterogenic development of chronic inflammation in LUTD. High-priority research questions were identified.
Seifalian A, Basma Z, Digesu A, et al., 2023, Polypropylene pelvic mesh: what went wrong and what will be of the future?, Biomedicines, Vol: 11, ISSN: 2227-9059
Background: Polypropylene (PP) pelvic mesh is a synthetic mesh made of PP polymer used to treat pelvic organ prolapse (POP). Its use has become highly controversial due to reports of serious complications. This research critically reviews the current management options for POP and PP mesh as a viable clinical application for the treatment of POP. The safety and suitability of PP material were rigorously studied and critically evaluated, with consideration to the mechanical and chemical properties of PP. We proposed the ideal properties of the ‘perfect’ synthetic pelvic mesh with emerging advanced materials. Methods: We performed a literature review using PubMed/Medline, Embase, Cochrane Library (Wiley) databases, and ClinicalTrials.gov databases, including the relevant keywords: pelvic organ prolapse (POP), polypropylene mesh, synthetic mesh, and mesh complications. Results: The results of this review found that although PP is nontoxic, its physical properties demonstrate a significant mismatch between its viscoelastic properties compared to the surrounding tissue, which is a likely cause of complications. In addition, a lack of integration of PP mesh into surrounding tissue over longer periods of follow up is another risk factor for irreversible complications. Conclusions: PP mesh has caused a rise in reports of complications involving chronic pain and mesh exposure. This is due to the mechanical and physicochemical properties of PP mesh. As a result, PP mesh for the treatment of POP has been banned in multiple countries, currently with no alternative available. We propose the development of a pelvic mesh using advanced materials including emerging graphene-based nanocomposite materials.
Tailor V, Bhide A, Khullar V, 2023, The Urinary Microbiome, Textbook of Female Urology and Urogynecology: Clinical Perspectives, Pages: 384-398, ISBN: 9780367700140
The development of next-generation sequencing methods has improved our ability to study the microbial communities that reside within human hosts. The microbiome describes the genetic material of these microbes. It is now well established that the microbiota can play a role in health and disease. The study of the bladder bacterial microbiota whilst relatively new has started to provide clues to the maintenance of bladder health. With further research, the knowledge could help establish the use of novel treatments for lower urinary tract symptoms.
Seifalian A, Kenyon J, Khullar V, 2022, Dysmenorrhoea: can medicinal cannabis bring new hope for a collective group of women suffering in pain, globally?, International Journal of Molecular Sciences, Vol: 23, ISSN: 1422-0067
Dysmenorrhoea effects up to 90% of women of reproductive age, with medical management options including over-the-counter analgesia or hormonal contraception. There has been a recent surge in medicinal cannabis research and its analgesic properties. This paper aims to critically investigate the current research of medicinal cannabis for pain relief and to discuss its potential application to treat dysmenorrhoea. Relevant keywords, including medicinal cannabis, pain, cannabinoids, tetrahydrocannabinol, dysmenorrhoea, and clinical trial, have been searched in the PubMed, EMBASE, MEDLINE, Google Scholar, Cochrane Library (Wiley) databases and a clinical trial website (clinicaltrials.gov). To identify the relevant studies for this paper, 84 papers were reviewed and 20 were discarded as irrelevant. This review critically evaluated cannabis-based medicines and their mechanism and properties in relation to pain relief. It also tabulated all clinical trials carried out investigating medicinal cannabis for pain relief and highlighted the side effects. In addition, the safety and toxicology of medicinal cannabis and barriers to use are highlighted. Two-thirds of the clinical trials summarised confirmed positive analgesic outcomes, with major side effects reported as nausea, drowsiness, and dry mouth. In conclusion, medicinal cannabis has promising applications in the management of dysmenorrhoea. The global medical cannabis market size was valued at USD 11.0 billion in 2021 and is expected to expand at a compound annual growth rate (CAGR) of 21.06% from 2022 to 2030. This will encourage academic as well as the pharmaceutical and medical device industries to study the application of medical cannabis in unmet clinical disorders.
Tailor V, Danckert N, Bhide A, et al., 2022, Studying the faecal microbiome of women presenting to urogynaecology, Publisher: SPRINGER LONDON LTD, Pages: 2916-2916, ISSN: 0937-3462
Patel M, Rahim A, Tailor V, et al., 2022, Chronic pelvic pain and associated symptomology: a new validated questionnaire., Publisher: SPRINGER LONDON LTD, Pages: 2918-2919, ISSN: 0937-3462
Asfour V, Wertheim D, Rahim A, et al., 2022, Anorectal Angle in Prolapse and Control Women, Publisher: SPRINGER LONDON LTD, Pages: S437-S438, ISSN: 0937-3462
Asfour V, Wertheim D, Digesu A, et al., 2022, Is Perineal Body Size Important in Prolapse?, Publisher: SPRINGER LONDON LTD, Pages: S435-S435, ISSN: 0937-3462
Karmarkar R, Digesu A, Fernando R, et al., 2022, Ultrasound assessment of urethral structure and bladder neck position in women with different parities, INTERNATIONAL UROGYNECOLOGY JOURNAL, Vol: 33, Pages: 613-618, ISSN: 0937-3462
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Patel M, Khullar V, 2021, Urogynaecology and Ehlers-Danlos syndrome, AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS, Vol: 187, Pages: 579-585, ISSN: 1552-4868
Asfour V, Gibbs K, Wertheim D, et al., 2021, Anal canal to pubis angle: a novel clinical ultrasound technique for the assessment of the anorectal region, INTERNATIONAL UROGYNECOLOGY JOURNAL, Vol: 32, Pages: 2421-2427, ISSN: 0937-3462
Rahim A, Bhide A, Mackdermott N, et al., 2021, MODE OF DELIVERY FOLLOWING OASIS: A 5-YEAR FOLLOW UP STUDY OF SUBSEQUENT DELIVERIES AFTER 3RD AND 4TH DEGREE VAGINAL TEARS., Publisher: WILEY, Pages: S42-S43, ISSN: 0733-2467
Derpapas A, Vijaya G, Nikolopoulos K, et al., 2021, The use of 3D ultrasound in comparing surgical techniques for posterior wall prolapse repair: a pilot randomised controlled trial, JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 41, Pages: 594-600, ISSN: 0144-3615
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Tailor VK, Morris E, Bhide AA, et al., 2021, Does cystoscopy method affect the investigation of bladder pain syndrome/interstitial cystitis?, INTERNATIONAL UROGYNECOLOGY JOURNAL, Vol: 32, Pages: 1229-1235, ISSN: 0937-3462
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Wali S, Bhide A, Khullar V, et al., 2021, Mode of delivery after obstetric anal sphincter injuries (OASIS), Publisher: WILEY, Pages: 53-53, ISSN: 1470-0328
Cartwright J, Frankin L, Tikkinen K, et al., 2021, Genome wide association study identifies two novel loci associated with female stress and urgency urinary incontinence, The Journal of Urology, ISSN: 0022-5347
Background:Genome-wide association studies (GWAS) have not identified replicable genetic risk loci for stress or urgency urinary incontinence.Methods:We carried out a discovery stage case control GWAS in three independent discovery cohorts of European women (n=8,979) for stress incontinence, urgency incontinence, and any incontinence phenotypes. We conducted replication in six additional studies of European ancestry (n=4,069). We collected bladder biopsies from women with incontinence to further investigate bladder expression of implicated genes and pathways (n=50) and used symptom questionnaires for phenotyping. We conducted meta-analyses using inverse variance fixed effects models in METAL, and whole transcriptome analyses using Affymetrix arrays, with replication with TaqMan PCR.Results:In the discovery stage we identified 16 single nucleotide polymorphisms (SNPs) genotyped or imputed at five loci that reached genome-wide significance (p<5x10-8). In replication, rs138724718 on chromosome 2, near the macrophage receptor with collagenous structure (MARCO) gene (replication p=0.003) associated with stress incontinence. In addition, rs34998271 on chromosome 6 near the Endothelin 1 (EDN1) gene (replication p=0.0008) associated with urgency incontinence. In combined meta-analyses of discovery and replication cohorts, associations with genome-wide significance for these two SNPs were confirmed. Transcriptomics analyses showed differential expression of 7 of 19 genes in the endothelin pathway between stress and urgency incontinence (p<0.0001).Conclusion:We uncovered two new risk loci near the genes Endothelin 1 (EDN1), associated with urgency incontinence and Macrophage Receptor with Collagenous Structure (MARCO), associated with stress incontinence. These loci are biologically plausible given their roles in smooth muscle contraction and innate host defense respectively.
Bhide A, Tailor V, Rahim A, et al., 2020, Results of bladder instillations for bladder pain syndrome: audit of our current practice, Publisher: SPRINGER LONDON LTD, Pages: S140-S141, ISSN: 0937-3462
Thiagamoorthy G, Dua A, Araklitis G, et al., 2020, Post-operative pain after pelvic organ prolapse surgery (POPPOP). Double blind randomised multicentre study to assess the effect of local anaesthesia during vaginal hysterectomy, Publisher: SPRINGER LONDON LTD, Pages: S1-S2, ISSN: 0937-3462
Millar O, Patel M, Beattie-Spanjol S, et al., 2020, Pelvic pain is common among women with bladder and bowel symptoms, Publisher: SPRINGER LONDON LTD, Pages: S104-S104, ISSN: 0937-3462
Bhide A, Tailor V, Rahim A, et al., 2020, Retrospective analysis of mesh complication cases: our experience, Publisher: SPRINGER LONDON LTD, Pages: S231-S232, ISSN: 0937-3462
Beattie-Spanjol S, Millar O, Ahmad A, et al., 2020, Abnormal immunology is associated with recurrent urinary tract infections, Publisher: SPRINGER LONDON LTD, Pages: S138-S139, ISSN: 0937-3462
Rahim A, Ahmad A, Tailor V, et al., 2020, Intra- and inter-observer reliability of perineal body volume measurements with 3-dimensional transperineal ultrasound, Publisher: SPRINGER LONDON LTD, Pages: S103-S103, ISSN: 0937-3462
Tailor V, Morris E, Bhide A, et al., 2020, Does cystoscopy method affect the investigation of bladder pain syndrome (BPS)?, Publisher: SPRINGER LONDON LTD, Pages: S78-S78, ISSN: 0937-3462
Patel M, Morris E, Bhide A, et al., 2020, Systematic review of the accuracy of ultrasound as the method of measuring bladder wall thickness in the diagnosis of detrusor overactivity., Publisher: SPRINGER LONDON LTD, Pages: S31-S32, ISSN: 0937-3462
Millar O, Patel M, Beattie-Spanjol S, et al., 2020, Pain in women from urogynaecology clinics, is it just in the pelvis?, Publisher: SPRINGER LONDON LTD, Pages: S121-S122, ISSN: 0937-3462
Karmarkar R, Digesu A, Fernando R, et al., 2020, Urethral sphincter volume and urodynamic diagnosis, INTERNATIONAL UROGYNECOLOGY JOURNAL, Vol: 31, Pages: 2589-2594, ISSN: 0937-3462
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