Publications by authors named "Rufus Cartwright"

99 Publications

ARTS: A Large, International Trial of Thromboprophylaxis in Intra-abdominal, Gynecologic, and Urologic Surgery.

Eur Urol Focus 2021 Sep 21. Epub 2021 Sep 21.

Department of Urology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Department of Surgery, South Karelian Central Hospital, Lappeenranta, Finland. Electronic address:

ARTS will be the first trial to compare anticoagulation with a direct oral anticoagulant (apixaban) versus no anticoagulation among patients undergoing intra-abdominal, gynecologic, or urologic surgery at sufficiently similar risk of deep vein thrombosis or pulmonary embolism and major bleeding.
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http://dx.doi.org/10.1016/j.euf.2021.08.010DOI Listing
September 2021

Host-biomaterial interactions in mesh complications after pelvic floor reconstructive surgery.

Nat Rev Urol 2021 Sep 20. Epub 2021 Sep 20.

Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences (NDORMS), University of Oxford, Oxford, UK.

Polypropylene (PPL) mesh is widely used in pelvic floor reconstructive surgery for prolapse and stress urinary incontinence. However, some women, particularly those treated using transvaginal PPL mesh placement for prolapse, experience intractable pain and mesh exposure or extrusion. Explanted tissue from patients with complications following transvaginal implantation of mesh is typified by a dense fibrous capsule with an immune cell-rich infiltrate, suggesting that the host immune response has a role in transvaginal PPL mesh complications through the separate contributions of the host (patient), the biological niche within which the material is implanted and biomaterial properties of the mesh. This immune response might be strongly influenced by both the baseline inflammatory status of the patient, surgical technique and experience, and the unique hormonal, immune and microbial tissue niche of the vagina. Mesh porosity, surface area and stiffness also might have an effect on the immune and tissue response to transvaginal mesh placement. Thus, a regulatory pathway is needed for mesh development that recognizes the roles of host and biological factors in driving the immune response to mesh, as well as mandatory mesh registries and the longitudinal surveillance of patients.
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http://dx.doi.org/10.1038/s41585-021-00511-yDOI Listing
September 2021

Laparoscopic sacrohysteropexy versus vaginal hysterectomy and apical suspension: 7-year follow-up of a randomized controlled trial.

Int Urogynecol J 2021 Aug 23. Epub 2021 Aug 23.

Department of Urogynaecology, Women's Centre, The John Radcliffe Hospital, Oxford University Hospitals, Headington, Oxford, OX3 9FR, UK.

Introduction And Hypothesis: Laparoscopic mesh sacrohysteropexy offers a uterine-sparing alternative to vaginal hysterectomy with apical suspension, although randomised comparative data are lacking. This study was aimed at comparing the long-term efficacy of laparoscopic mesh sacrohysteropexy and vaginal hysterectomy with apical suspension for the treatment of uterine prolapse.

Methods: A randomised controlled trial comparing laparoscopic mesh sacrohysteropexy and vaginal hysterectomy with apical suspension for the treatment of uterine prolapse was performed, with a minimum follow-up of 7 years. The primary outcome was reoperation for apical prolapse. Secondary outcomes included patient-reported mesh complications, Pelvic Organ Prolapse Quantification, Patient Global Impression of Improvement in prolapse symptoms and the International Consultation on Incontinence Questionnaire Vaginal Symptoms, Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) and PISQ-12 questionnaires.

Results: A total of 101 women were randomised and 62 women attended for follow-up at a mean of 100 months postoperatively (range 84-119 months). None reported a mesh-associated complication. The risk of reoperation for apical prolapse was 17.2% following vaginal hysterectomy (VH) and 6.1% following laparoscopic mesh sacrohysteropexy (LSH; relative risk 0.34, 95% CI 0.07-1.68, p = 0.17). Laparoscopic sacrohysteropexy was associated with a statistically significantly higher apical suspension (POP-Q point C -5 vs -4.25, p = 0.02) and longer total vaginal length (9 cm vs 6 cm, p < 0.001). There was no difference in the change in ICIQ-VS scores between the two groups (ICIQ-VS change -22 vs -25, p = 0.59).

Conclusion: Laparoscopic sacrohysteropexy and vaginal hysterectomy with apical suspension have comparable reoperation rates and subjective outcomes. Potential advantages of laparoscopic sacrohysteropexy include a lower risk of apical reoperation, greater apical support and increased total vaginal length.
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http://dx.doi.org/10.1007/s00192-021-04932-6DOI Listing
August 2021

Genome-Wide Association Study Identifies Two Novel Loci Associated with Female Stress and Urgency Urinary Incontinence.

J Urol 2021 09 27;206(3):679-687. Epub 2021 Apr 27.

Institute for Reproductive and Developmental Biology (IRDB), Imperial College London, UK.

Purpose: Genome-wide association studies have not identified replicable genetic risk loci for stress or urgency urinary incontinence.

Materials And Methods: We carried out a discovery stage, case control, genome-wide association study in 3 independent discovery cohorts of European women (8,979) for stress incontinence, urgency incontinence, and any incontinence phenotypes. We conducted replication in 6 additional studies of European ancestry (4,069). We collected bladder biopsies from women with incontinence (50) to further investigate bladder expression of implicated genes and pathways and used symptom questionnaires for phenotyping. We conducted meta-analyses using inverse variance fixed effects models and whole transcriptome analyses using Affymetrix® arrays with replication with TaqMan® polymerase chain reaction.

Results: In the discovery stage, we identified 16 single nucleotide polymorphisms genotyped or imputed at 5 loci that reached genome-wide significance (p <5×10). In replication, rs138724718 on chromosome 2 near the macrophage receptor with collagenous structure () gene (replication p=0.003) was associated with stress incontinence. In addition, rs34998271 on chromosome 6 near the endothelin 1 () gene (replication p=0.0008) was associated with urgency incontinence. In combined meta-analyses of discovery and replication cohorts, associations with genome-wide significance for these 2 single nucleotide polymorphisms were confirmed. Transcriptomics analyses showed differential expression of 7 of 19 genes in the endothelin pathway between stress and urgency incontinence (p <0.0001).

Conclusions: We uncovered 2 new risk loci near the genes endothelin 1 (), associated with urgency incontinence, and macrophage receptor with collagenous structure (), associated with stress incontinence. These loci are biologically plausible given their roles in smooth muscle contraction and innate host defense, respectively.
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http://dx.doi.org/10.1097/JU.0000000000001822DOI Listing
September 2021

Systematic review and meta-analysis of genetic association studies of pelvic organ prolapse.

Int Urogynecol J 2021 Apr 24. Epub 2021 Apr 24.

Department of Epidemiology & Biostatistics, Imperial College London, Norfolk Place, London, UK.

Introduction And Hypothesis: Family and twin studies demonstrate that pelvic organ prolapse (POP) is heritable, but the genetic etiology is poorly understood. This review aimed to identify genetic loci and specific polymorphisms associated with POP, while assessing the strength, consistency, and risk of bias among reported associations.

Methods: Updating an earlier systematic review, PubMed and HuGE Navigator as well as relevant conference abstracts were searched using genetic and phenotype keywords from 2015 to 2020. Screening and data extraction were performed in duplicate. Fixed and random effects meta-analyses were conducted using co-dominant models of inheritance. We assessed credibility of pooled associations using interim Venice criteria.

Results: We screened 504 new abstracts and included 46 published and 7 unpublished studies. In pooled analyses we found significant associations for four polymorphisms: rs2228480 at the ESR1 gene (OR 0.67 95% CI 0.46-0.98, I = 0.0%, Venice rating BAB), rs12589592 at the FBLN5 gene (OR 1.46 95% CI 1.11-1.82, I = 36.3%, Venice rating BBB), rs484389 in the PGR gene (OR 0.61 95% CI 0.39-0.96, I = 32.4%, Venice rating CBB), and rs1800012 at the COL1A1 gene (OR 0.80 95% CI 0.66-0.96, I = 0.0%, Venice rating BAB). Further credible novel variants have also been recently identified in genome-wide association studies.

Conclusion: The genetic contributions to POP remain poorly understood. Several biologically plausible variants have been identified, but much work is required to establish the role of these genes in the pathogenesis of POP or to establish a role for genetic testing in clinical practice.
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http://dx.doi.org/10.1007/s00192-021-04782-2DOI Listing
April 2021

Genetic variation in cervical preinvasive and invasive disease: a genome-wide association study.

Lancet Oncol 2021 04;22(4):548-557

Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK; Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK; West London Gynaecological Cancer Centre, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK. Electronic address:

Background: Most uterine cervical high-risk human papillomavirus (HPV) infections are transient, with only a small fraction developing into cervical cancer. Family aggregation studies and heritability estimates suggest a significant inherited genetic component. Candidate gene studies and previous genome-wide association studies (GWASs) report associations between the HLA region and cervical cancer. Adopting a genome-wide approach, we aimed to compare genetic variation in women with invasive cervical cancer and cervical intraepithelial neoplasia (CIN) grade 3 with that in healthy controls.

Methods: We did a GWAS in a cohort of unrelated European individuals using data from UK Biobank, a population-based cohort including 273 377 women aged 40-69 years at recruitment between March 13, 2006, and Oct 1, 2010. We used an additive univariate logistic regression model to analyse genetic variants associated with invasive cervical cancer or CIN3. We sought replication of candidate associations in FinnGen, a large independent dataset of 128 123 individuals. We also did a two-sample mendelian randomisation approach to explore the role of risk factors in the genetic risk of cervical cancer.

Findings: We included 4769 CIN3 and invasive cervical cancer case samples and 145 545 control samples in the GWAS. Of 9 600 464 assayed and imputed single-nucleotide polymorphisms (SNPs), six independent variants were associated with CIN3 and invasive cervical cancer. These included novel loci rs10175462 (PAX8; odds ratio [OR] 0·87, 95% CI 0·84-0·91; p=1·07 × 10) and rs27069 (CLPTM1L; 0·88, 0·84-0·92; p=2·51 × 10), and previously reported signals at rs9272050 (HLA-DQA1; 1·27, 1·21-1·32; p=2·51 × 10), rs6938453 (MICA; 0·79, 0·75-0·83; p=1·97 × 10), rs55986091 (HLA-DQB1; 0·66, 0·60-0·72; p=6·42 × 10), and rs9266183 (HLA-B; 0·73, 0·64-0·83; p=1·53 × 10). Three SNPs were replicated in the independent Finnish dataset of 1648 invasive cervical cancer cases: PAX8 (rs10175462; p=0·015), CLPTM1L (rs27069; p=2·54 × 10), and HLA-DQA1 (rs9272050; p=7·90 × 10). Mendelian randomisation further supported the complementary role of smoking (OR 2·46, 95% CI 1·64-3·69), older age at first pregnancy (0·80, 0·68-0·95), and number of sexual partners (1·95, 1·44-2·63) in the risk of developing cervical cancer.

Interpretation: Our results provide new evidence for the genetic susceptibility to cervical cancer, specifically the PAX8, CLPTM1L, and HLA genes, suggesting disruption in apoptotic and immune function pathways. Future studies integrating host and viral, genetic, and epigenetic variation, could further elucidate complex host-viral interactions.

Funding: NIHR Imperial BRC Wellcome 4i Clinician Scientist Training Programme.
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http://dx.doi.org/10.1016/S1470-2045(21)00028-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008734PMC
April 2021

Female pelvic medicine and reconstructive surgery challenges on behalf of the Collaborative Research in Pelvic Surgery Consortium: managing complicated cases.

Int Urogynecol J 2021 Jun 13;32(6):1373-1377. Epub 2021 Feb 13.

Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, NY, USA.

This case presents the work-up and management of a patient experiencing acute kidney injury, urinary retention, and neuropathy following surgery for pelvic organ prolapse and stress urinary incontinence. Four international experts provide their evaluation of and approach to this complex case.
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http://dx.doi.org/10.1007/s00192-021-04702-4DOI Listing
June 2021

Sacrocolpopexy tends to be superior to transvaginal mesh surgery.

BJOG 2021 01 3;128(1):24. Epub 2020 Aug 3.

Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

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http://dx.doi.org/10.1111/1471-0528.16407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754300PMC
January 2021

Long-term mesh complications and reoperation after laparoscopic mesh sacrohysteropexy: a cross-sectional study.

Int Urogynecol J 2020 Dec 3;31(12):2595-2602. Epub 2020 Jul 3.

Urogynaecology and Pelvic Floor Unit, University College London Hospitals, Clinic 2, Lower Ground Floor, EGA Wing, 235 Euston Road, London, NW12BU, UK.

Introduction And Hypothesis: The paucity of long-term safety and efficacy data to support laparoscopic mesh sacrohysteropexy is noteworthy given concerns about the use of polypropylene mesh in pelvic floor surgery. This study is aimed at determining the incidence of mesh-associated complications and reoperation following this procedure.

Methods: This was a cross-sectional postal questionnaire study of women who underwent laparoscopic mesh sacrohysteropexy between 2010 and 2018. Potential participants were identified from surgical databases of five surgeons at two tertiary urogynaecology centres in the UK. The primary outcome was patient-reported mesh complication requiring removal of hysteropexy mesh. Secondary outcomes included other mesh-associated complications, reoperation rates and Patient Global Impression of Improvement (PGI-I) in prolapse symptoms. Descriptive statistics and Kaplan-Meier survival analyses were used.

Results: Of 1,766 eligible participants, 1,121 women responded (response proportion 63.5%), at a median follow-up of 46 months. The incidence of mesh complications requiring removal of hysteropexy mesh was 0.4% (4 out of 1,121). The rate of chronic pain service use was 1.8%, and newly diagnosed systemic autoimmune disorders was 5.8%. The rate of reoperation for apical prolapse was 3.7%, and for any form of pelvic organ prolapse it was 13.6%. For PGI-I, 81.4% of patients were "much better" or "very much better".

Conclusions: Laparoscopic mesh sacrohysteropexy has a low incidence of reoperation for mesh complications and apical prolapse, and a high rate of patient-reported improvement in prolapse symptoms. With appropriate clinical governance measures, the procedure offers an alternative to vaginal hysterectomy with apical suspension. However, long-term comparative studies are still required.
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http://dx.doi.org/10.1007/s00192-020-04396-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679361PMC
December 2020

An International Survey on the Use of Thromboprophylaxis in Urological Surgery.

Eur Urol Focus 2021 May 16;7(3):653-658. Epub 2020 Jun 16.

Departments of Urology and Public Health, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. Electronic address:

Background: The use of perioperative thromboprophylaxis in urological surgery is common but not standardized.

Objective: To characterize international practice variation in thromboprophylaxis use in urological surgery.

Design, Setting, And Participants: We conducted a scenario-based survey addressing the use of mechanical and pharmacological thromboprophylaxis in urological cancer procedures (radical cystectomy [RC], radical prostatectomy [RP], and radical nephrectomy [RN]) among practicing urologists in Canada, Finland, and Japan. The survey presented patient profiles reflecting a spectrum of risk for venous thromboembolism; the respondents described their clinical practice.

Outcome Measurements And Statistical Analysis: The proportion of respondents who routinely used (1) mechanical, (2) pharmacological, and (3) extended pharmacological prophylaxis was stratified by procedure. A logistic regression identified characteristics associated with thromboprophylaxis use.

Results And Limitations: Of 1051 urologists contacted, 570 (54%) participated in the survey. Japanese urologists were less likely to prescribe pharmacological prophylaxis than Canadian or Finnish urologists (p < 0.001 for all procedures). Canadian and Finnish urologists exhibited large variation for extended pharmacological prophylaxis for RP and RN. Finnish urologists were most likely to prescribe extended prophylaxis versus Canadian and Japanese urologists (RC 98%, 84%, and 26%; Open RP 25%, 8%, and 3%; robotic RP 11%, 9%, and 0%; and RN 43%, 7%, and 1%, respectively; p < 0.001 for each procedure). Less variation was found regarding the prescription of mechanical prophylaxis, which was most commonly used until ambulation or discharge. The length of hospital stay was longer in Japan and may bias estimates of extended prophylaxis in Japan.

Conclusions: We found large variation in clinical practice regarding pharmacological thromboprophylaxis within and between countries. Knowledge translation of evidence-based guidelines may reduce problematic international variation in practice.

Patient Summary: Use of medications to decrease blood clots after urological cancer surgery differs within and between countries. Closer adherence to urology guidelines addressing the prevention of blood clots may decrease this variation and improve patient outcomes.
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http://dx.doi.org/10.1016/j.euf.2020.05.015DOI Listing
May 2021

A novel technique for complete laparoscopic excision of a transobturator sling with lower urinary tract mesh erosion.

Int Urogynecol J 2020 04 26;31(4):839-841. Epub 2020 Feb 26.

John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, UK.

Introduction And Hypothesis: To demonstrate a novel technique for complete laparoscopic removal of a transobturator sling for mesh erosion involving a large area of the urethra and bladder neck, without the need for concomitant vaginal dissection.

Method: A 56-year-old woman had a transobturator sling inserted for stress urinary incontinence (SUI) in 2009. In 2017, 8 years following surgery, she experienced groin pain, exacerbated by exercise, and developed recurrent urinary tract infections with dysuria and urethral pain. A cystoscopy demonstrated mesh erosion from the midurethra to bladder neck with a 2-cm calculus formed around the mesh. After careful counselling and discussion at a multi-disciplinary meeting, a decision was made to proceed with laparoscopy with a view to remove the mesh completely. The mesh was removed from the points of erosion into the urethra through a total laparoscopic procedure. The patient made a good recovery with no ongoing pain or voiding difficulties.

Conclusion: Combined approaches for complete excision of transobturator slings, including bilateral inguinal dissection, are relatively morbid with prolonged recovery time and in most centres will require involvement of plastic surgeons. The laparoscopic approach not only allows for the mesh to be removed in total (including the intramural portion of the mesh), but also provides magnified views compared with open surgery and thus allows for better identification of planes and dissection. It also has the added benefit of avoiding vaginal incisions and therefore reducing the risk of fistula formation between the urethra/bladder and vagina.
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http://dx.doi.org/10.1007/s00192-020-04264-xDOI Listing
April 2020

GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI.

Sci Adv 2019 09 4;5(9):eaaw3095. Epub 2019 Sep 4.

Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.

Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.
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http://dx.doi.org/10.1126/sciadv.aaw3095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904961PMC
September 2019

Laparoscopic complete sacrocolpopexy mesh removal for right-sided gluteal pain and recurrent mesh erosion.

Int Urogynecol J 2020 02 3;31(2):411-413. Epub 2019 Sep 3.

John Radcliffe Hospital, Headley Way, Headington, Oxford, OX3 9DU, UK.

Aim Of Video: The aim was to demonstrate laparoscopic complete excision of sacrocolpopexy mesh from a 65-year-old woman who had presented with delayed onset of persistent right-sided gluteal pain.

Method: The patient was referred to our unit, having undergone a laparoscopic sacrocolpopexy for vault prolapse 7 years earlier, with a type 1 polypropylene mesh. Four years after the primary surgery, she first noticed symptoms of spontaneous vaginal pain together with deep dyspareunia, and right-sided gluteal pain. Clinical examination revealed mesh erosion at the vaginal vault. This was managed at her local hospital, with excision of the small exposed portion of the mesh and over sewing, from a vaginal approach. She continued to be symptomatic following this procedure. When her symptoms still failed to improve 3 years later, a tertiary referral was made to our unit. At laparoscopy, minimal adhesions between the bowel and the mesh were noted and divided. After carefully dissecting the right ureter and reflecting the bladder, the entire sacrocolpopexy mesh was removed with its ProTack fasteners. The entire specimen was retrieved in one piece through the open vault and the vagina was sutured with 2.0
Conclusion: This video demonstrates the steps needed to undertake complete laparoscopic sacrocolpopexy mesh excision, which should be feasible for skilled laparoscopists. This approach has advantages over the open approach, with good access and visualisation of the entire course of the mesh, and more rapid recovery for the patient.
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http://dx.doi.org/10.1007/s00192-019-04088-4DOI Listing
February 2020

Abnormal vaginal microbiome associated with vaginal mesh complications.

Neurourol Urodyn 2019 11 11;38(8):2255-2263. Epub 2019 Aug 11.

Department of Urogynaecology, St. Mary's Hospital, Imperial College London, London, United Kingdom.

Aims: To identify differences in the vaginal microbiomes of women after transvaginal mesh (TVM) surgery for pelvic organ prolapse with and without mesh-associated complications.

Methods: Patients with complications were eligible as cases, patients without as controls. DNA was isolated and the V1-2 region of the 16S ribosomal RNA gene was amplified and sequenced. Overall richness was quantified using Chao1. Overall diversity was expressed as Shannon diversity and screened for group differences using analysis of variance. Multivariate differences among groups were evaluated with functions from R.

Results: We recruited 14 patients after mesh exposure, 5 after contraction, and 21 as controls. The average number of operational taxonomic unit was 74.79 (SD ± 63.91) for controls, 57.13 (SD ± 58.74) after exposures, and 92.42 (SD ± 50.01) after contractions. Total 89.6% of bacteria in controls, 86.4% in previous exposures, and 81.3% in contractions were classified as either Firmicutes, Proteobacteria, or Actinobacteria (P < .001). Veillonella spp. was more abundant in patients after contraction (P = .045). The individual microbiomes varied, and we did not detect any significant differences in richness but a trend towards higher diversity with complications.

Conclusions: The presence of Veillonella spp. could be associated with mesh contraction. Our study did not identify vaginal microbiotic dysbiosis as a factor associated with exposure. Larger cohort studies would be needed to distinguish the vaginal microbiome of women predisposed to mesh-related complications for targeted phenotyping of patients who could benefit from TVM surgery.
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http://dx.doi.org/10.1002/nau.24129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6852108PMC
November 2019

The Impact of Nocturia on Mortality: A Systematic Review and Meta-Analysis.

J Urol 2020 03 31;203(3):486-495. Epub 2019 Jul 31.

Department of Urology, University of Helsinki, Helsinki, Finland.

Purpose: Nocturia (waking from sleep at night to void) is a common cause of sleep disruption associated with increased comorbidity and impaired quality of life. However, its impact on mortality remains unclear. We performed a systematic review and meta-analysis to evaluate the association of nocturia with mortality as a prognostic factor and a causal risk factor.

Materials And Methods: We searched PubMed®, Scopus®, CINAHL® (Cumulative Index of Nursing and Allied Health Literature) and major conference abstracts up to December 31, 2018. Random effects meta-analyses were done to address the adjusted RR of mortality in people with nocturia. Meta-regression was performed to explore potential determinants of heterogeneity, including the risk of bias. We applied the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) framework to rate the quality of evidence for nocturia as a prognostic risk factor for mortality and separately as a cause of mortality.

Results: Of the 5,230 identified reports 11 observational studies proved eligible for inclusion. To assess nocturia 10 studies used symptom questionnaires and 1 used frequency-volume charts. Nocturia was defined as 2 or more episodes per night in 6 studies (55%) and as 3 or more episodes per night in 5 (45%). Pooled estimates demonstrated a RR of 1.27 (95% CI 1.16-1.40, I=48%) with an absolute 1.6% and 4.0% 5-year mortality difference in individuals 60 and 75 years old, respectively. The pooled estimates of relative risk did not differ significantly across varying age, gender, followup, nocturia case definition, risk of bias or study region. We rated the quality of evidence for nocturia as a prognostic factor as moderate and as a cause of mortality as very low.

Conclusions: Nocturia is probably associated with an approximately 1.3-fold increased risk of death.
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http://dx.doi.org/10.1097/JU.0000000000000463DOI Listing
March 2020

The Impact of Nocturia on Falls and Fractures: A Systematic Review and Meta-Analysis.

J Urol 2020 04 26;203(4):674-683. Epub 2019 Jul 26.

Department of Urology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Purpose: Although nocturia is associated with various comorbidities, its impact on falls and fractures remains unclear. We performed a systematic review and meta-analysis to evaluate the association between nocturia and falls and fractures as a prognostic and as a causal risk factor.

Materials And Methods: We searched PubMed®, Scopus®, CINAHL (Cumulative Index to Nursing and Allied Health Literature) and abstracts of major urological meetings up to December 31, 2018. We conducted random effects meta-analyses of adjusted relative risks of falls and fractures. We applied the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate the quality of evidence for nocturia as a prognostic and causal factor of falls and fractures.

Results: Among 5,230 potential reports 9 observational longitudinal studies provided data on the association between nocturia and falls or fractures (1 for both, 4 for falls, 4 for fractures). Pooled estimates demonstrated a risk ratio of 1.20 (95% CI 1.05-1.37, I=51.7%, annual risk difference 7.5% among the elderly) for association between nocturia and falls and 1.32 (95% CI 0.99-1.76, I=57.5%, annual risk difference 1.2%) for association between nocturia and fractures. Subgroup analyses showed no significant effect modification by age, gender, followup time, nocturia case definition or risk of bias. We rated the quality of evidence for nocturia as a prognostic factor as moderate for falls and low for fractures, and as very low as a cause of falls/fractures.

Conclusions: Nocturia is probably associated with an approximately 1.2-fold increased risk of falls and possibly an approximately 1.3-fold increased risk of fractures.
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http://dx.doi.org/10.1097/JU.0000000000000459DOI Listing
April 2020

Complete laparoscopic removal of retropubic midurethral tape (tension-free vaginal tape) from the obturator nerve: a multidisciplinary approach.

Int Urogynecol J 2019 11 29;30(11):1985-1986. Epub 2019 Jun 29.

Department of Gynaecology, Women's Centre, John Radcliffe Hospital, Headley Way, Oxford, OX3 9DU, UK.

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http://dx.doi.org/10.1007/s00192-019-04016-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834749PMC
November 2019

Surgical interventions for stress urinary incontinence.

BMJ 2019 06 5;365:l2350. Epub 2019 Jun 5.

John Radcliffe Hospital, Oxford OX3 8HU, UK

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http://dx.doi.org/10.1136/bmj.l2350DOI Listing
June 2019

Mesh-related complications of laparoscopic sacrocolpopexy.

Int Urogynecol J 2019 09 30;30(9):1475-1481. Epub 2019 Apr 30.

Oxford University Hospital, Oxford, UK.

Introduction And Hypothesis: Apical vaginal support for post-hysterectomy vault prolapse can be provided by vaginal, abdominal, or laparoscopic routes. Sacrocolpopexy is associated with higher satisfaction rates and a lower re-operation rate than vaginal sacrospinous fixation. The laparoscopic approach can reduce hospital stay and blood loss. There are concerns about the use of mesh in urogynaecological procedures, but limited data indicate a low mesh complication rate with sacrocolpopexy (0-5%). This study was aimed at establishing the incidence of complications following laparoscopic sacrocolpopexy.

Methods: We carried out a retrospective cohort study of patients who underwent laparoscopic sacrocolpopexy at a large tertiary hospital. Cases were identified from coding data, theatre logs and the national urogynaecology procedure database. Data were gathered from theatre records, patient notes and the national database. Demographic data, concomitant procedures performed, duration of surgery, intra-operative complications, change in pelvic organ prolapse quantification point C, duration of stay, late complications and further urogynaecological surgery were assessed.

Results: A total of 660 patients underwent laparoscopic sacrocolpopexy between 2005 and 2017 (median time from surgery 4 years 3 months). Five cases (0.7%) developed vaginal mesh exposure. Two were successfully managed conservatively with topical oestrogen. Three required surgical excision of the mesh. Four patients (0.6%) presented with erosion of non-absorbable vaginal sutures. Two were successfully managed conservatively with topical oestrogen and oral antibiotics. Two were managed with vaginal suture excision.

Conclusions: This large series suggests that laparoscopic sacrocolpopexy might confer a low risk of mesh exposure. Together with good anatomical and patient-reported outcomes, laparoscopic sacrocolpopexy is a safe option for patients presenting with post-hysterectomy vault prolapse.
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http://dx.doi.org/10.1007/s00192-019-03952-7DOI Listing
September 2019

The impact of bariatric surgery on urinary incontinence: a systematic review and meta-analysis.

Int Urogynecol J 2019 08 26;30(8):1225-1237. Epub 2019 Apr 26.

Department of Urogynaecology, St Mary's Hospital, London, UK.

Introduction And Hypothesis: Obesity and overweight are strongly associated with stress and urgency urinary incontinence, and weight loss has been associated with improvement in urinary incontinence. We aimed to measure pooled effect sizes for different weight loss procedures on incontinence-specific quality of life and incontinence cure rate in a systematic review and meta-analysis.

Methods: MEDLINE, Embase and the Cochrane library were searched using a pre-defined strategy for relevant cohort studies. Random effects meta-analyses were conducted for the weighted mean difference for urinary quality of life scores and weighted overall pooled estimates for proportions of women cured. We explored heterogeneity using meta-regression, testing the type of bariatric surgery and change in BMI as predictors of effect size. The studies were categorised as either low or high risk of bias using a novel instrument specifically designed for longitudinal symptom research studies.

Results: Twenty-three studies (n = 3,225) were included. Incontinence-specific quality of life scores were improved by 14% (weighted mean difference = -14.79; CI = -18.47 to -11.11; I = 87.1%); the proportion of women cured of any urinary incontinence was 59% (95% CI = 51 to 66%) and the proportion of women cured of stress urinary incontinence was 55% (95% CI = 40 to 70%).

Conclusions: Bariatric surgery results in clinically meaningful improvements in incontinence-specific quality of life. Current data are limited by both short-term follow-up and unexplained heterogeneity among studies.
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http://dx.doi.org/10.1007/s00192-018-03865-xDOI Listing
August 2019

Antenatal corticosteroid therapy (ACT) and size at birth: A population-based analysis using the Finnish Medical Birth Register.

PLoS Med 2019 02 26;16(2):e1002746. Epub 2019 Feb 26.

Department of Epidemiology and Biostatistics, Imperial College London, London, United Kingdom.

Background: Antenatal corticosteroid therapy (ACT) is used clinically to prepare the fetal lung for impending preterm birth, but animal and human studies link corticosteroids to smaller birth size. Whether ACT is associated with birth size is debated; therefore, we assessed differences in birth size in treated versus untreated pregnancies.

Methods And Findings: This observational register-based study used data from the Finnish Medical Birth Register (FMBR) covering all births in Finland (January 1, 2006-December 31, 2010). We used unadjusted and adjusted regression analyses as well as propensity score matching (PSM) to analyze whether birth size differed by ACT exposure. PSM provides a stringent comparison, as subsamples were created matched on baseline and medical characteristics between treated and untreated women. All analyses were stratified by timing of birth. The primary study outcome was birth size: birth weight (BWT), birth length (BL), ponderal index (PI), and head circumference (HC) measured immediately after birth and recorded in the FMBR. Additional analyses explored indicators of neonatal health in relation to ACT exposure and birth size. A total of 278,508 live-born singleton births with ≥24 gestational completed weeks were registered in the FMBR during the 5-year study period. Over 4% of infants were born preterm, and 4,887 women were treated with ACT (1.75%). More than 44% of the exposed infants (n = 2,173) were born at term. First, results of unadjusted regression analyses using the entire sample showed the greatest reductions in BWT as compared to the other analytic methods: very preterm -61.26 g (±SE 24.12, P < 0.01), preterm -232.90 g (±SE 17.24, P < .001), near term -171.50 g (±SE 17.52, P < .001), and at term -101.95 g (±SE 10.89, P < .001). Second, using the entire sample, regression analyses adjusted for baseline and medical conditions showed significant differences in BWT between exposed and unexposed infants: very preterm -61.54 g (±SE 28.62, P < .03), preterm -222.78 g (±SE 19.64, P < .001), near term -159.25 g (±SE 19.14, P < .001), and at term -91.62 g (±SE 11.86, P < .03). Third, using the stringent PSM analyses based on matched subsamples, infants exposed to ACT weighed less at birth: -220.18 g (±SE 21.43, P < .001), -140.68 g (±SE 23.09, P < .001), and -89.38 g (±SE 14.16, P < .001), born preterm, near term, and at term, respectively. Similarly, significant reductions in BL and HC were also observed using the three analytic methods. There were no differences among postterm infants regardless of analytic method. Likewise, we observed no differences with respect to PI. Additional analyses showed that exposed and unexposed infants had generally similar Apgar scores at birth, yet the ACT-treated infants received greater medical care during the first 7 days of life and beyond. Our study is mainly limited by lack of data in FMBR specifying the interval between treatment and birth as well as other potential confounders that could not be tested.

Conclusions: In this study, ACT was consistently associated with reduction in birth size for infants born preterm, near term, or at term. Further investigation is warranted alongside reevaluation of guidelines. Efforts need to be made to correctly identify and target patients who will deliver preterm. Reduced growth should be considered when deliberating early care decisions.
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http://dx.doi.org/10.1371/journal.pmed.1002746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390995PMC
February 2019

A laparoscopic technique for excision of retropubic midurethral sling arms eroding into the bladder.

Int Urogynecol J 2019 06 19;30(6):1013-1015. Epub 2019 Feb 19.

John Radcliffe Hospital, Oxford University Hospitals NHS Foundation Trust, Headley Way, Headington, Oxford, OX3 9DU, UK.

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http://dx.doi.org/10.1007/s00192-019-03886-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6511350PMC
June 2019

Long-term risks of stress and urgency urinary incontinence after different vaginal delivery modes.

Am J Obstet Gynecol 2019 02 1;220(2):181.e1-181.e8. Epub 2018 Nov 1.

Departments of Urology and Public Health, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. Electronic address:

Background: Although operative delivery increases the risk of immediate pelvic floor trauma, no previous studies have adequately compared directly the effects of different kinds of instrumental vaginal deliveries on stress urinary incontinence and/or urgency urinary incontinence.

Objective(s): The objectives of the study were to estimate and compare the impact of different kinds of vaginal deliveries, including spontaneous, vacuum, and forceps, on stress and urgency urinary incontinence.

Study Design: All women aged 20 years or older, living in 1 county in Norway were invited to participate in 2 surveys addressing stress and urgency urinary incontinence using validated questions, "Do you leak urine when you cough, sneeze, laugh, or lift something heavy?" and "Do you have involuntary loss of urine in connection with sudden and strong urge to void?" with response options yes or no. Incontinence data were linked to the Medical Birth Registry of Norway. For this study, we included only women who had a history of vaginal birth(s). Case definitions for stress and urgency urinary incontinence were moderate to severe based on Sandvik Severity Index (slight, moderate, severe). We adjusted analyses for age, parity, body mass index, and time since last delivery and addressed effect modification, including an age threshold of 50 years.

Results: The final analysis included 13,694 women of whom 12.7% reported stress urinary incontinence and 8.4% urgency urinary incontinence. Among women aged younger than 50 years, there was a statistically significant difference in the risk of stress urinary incontinence for forceps delivery (odds ratio, 1.42, 95% confidence interval, 1.09-1.86, absolute difference 5.0%) but not for vacuum (odds ratio, 0.80, 95% confidence interval, 0.59-1.09) when compared with spontaneous vaginal delivery. Among women aged younger than 50 years, forceps also had increased risk for stress urinary incontinence (odds ratio, 1.76, 95% confidence interval, 1.20-2.60) when compared with vacuum. There was no association of stress or urgency urinary incontinence with mode of delivery in women aged 50 years or older.

Conclusion: For women aged younger than 50 years, forceps delivery is associated with significant increased long-term risk of stress urinary incontinence compared with other vaginal deliveries.
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http://dx.doi.org/10.1016/j.ajog.2018.10.034DOI Listing
February 2019

Levator Ani avulsion: The histological composition of this site. A cadaveric study.

Neurourol Urodyn 2019 01 30;38(1):123-129. Epub 2018 Oct 30.

Department of Urogynaecology, St. Mary's Hospital, London, United Kingdom.

Introduction: The sonographic appearance of a levator muscle "avulsion" representing the literal detachment of the pubovisceral muscle (PVM) enthesis has been contested. The nature of the levator ani "avulsion" is still not fully understood. It is known, that the tensile strength of a tendon is dependent on collagen with increased synthesis of collagen occurring in tissue with increased mechanical load levels. This study aims to perform a quantitative histological evaluation of the PVM enthesis with or without the imaging finding of levator ani "avulsion" to determine if there is a difference in the proportion of muscle and collagen.

Method: Three-dimensional translabial ultrasound for PVM "avulsion" was performed on cadavers using a GE Voluson I with a 5-9 MHz electronic probe. Cadavers were meticulously dissected to identify the presence or absence of an anatomical avulsion. The PVM enthesis was excised for further histopathological processing and treated with three different colorations. Quantitative analysis using ImageJ software was conducted to compare tissue composition in samples with or without sonographic "avulsion." All stages were performed by two separate investigators blinded to each other's results. The results were analyzed using SPSS v24, IBM.

Results: Twenty-three PVM enthesis with histological staining were procured. Ultrasonographic "avulsions" were seen in 5/23 PVM enthesis. No anatomical avulsions were seen. There was no difference in the overall muscle or collagen content (Kruskal-Wallis, P = 0.864). The mean organized skeletal muscle content was 23% in the sonographic "avulsion" group versus 62% in the no "avulsion" group (Kruskall-Walis, P = 0.02). "Avulsions" were associated with a disorganized appearance at histology.

Conclusion: The tissue composition relating to the proportion of muscle and collagen was not significantly different in specimens with or without sonographic "avulsions." However, morphological differences were observed in the organization of the muscle fibres, which requires further evaluation.
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http://dx.doi.org/10.1002/nau.23847DOI Listing
January 2019

Outcomes after laparoscopic removal of retropubic midurethral slings for chronic pain.

Int Urogynecol J 2019 08 18;30(8):1323-1328. Epub 2018 Sep 18.

John Radcliffe Hospital, Oxford University Hospitals, Headley Way, Headington, Oxford, OX3 9DU, UK.

Introduction And Hypothesis: Midurethral slings (MUS) are an established treatment for stress urinary incontinence (SUI), with good objective outcomes and low rates of complications. However, large population-based registry studies highlighted long-term complications from polypropylene slings including erosion, dyspareunia and chronic pain. With recent highly negative media coverage, many women are presenting with chronic pain attributed to the mesh to request complete removal. The available literature provides limited evidence on safety, symptom resolution and incontinence following MUS removal.

Methods: We identified all patients who underwent laparoscopic removal of MUS mesh at our hospital between 2011 and 2016. We extracted data from medical records to assess operative safety and contacted all patients by questionnaire that incorporated pain scales, symptom severity and satisfaction.

Results: A total of 56 women were assessed. Removal occurred at a median of 44 months following sling insertion (range 3-192). Mean operative time was 74 min (range 44-132). Two patients were returned to theatre (one at 24 hours and one at 14 days) to evacuate a retropubic haematoma, but no visceral injuries occurred. The median inpatient stay was 2 days (range 1-7). Of the 46% of patients who returned the questionnaire (n = 26), 88% said they would recommend the procedure. There was a median 6-point decrease in pain scores (10-point numerical scale, p < 0.0001); 44.6% reported worsening SUI, more common with removal of the suburethral mesh [odds ratio (OR) 10.72 95% confidence interval (CI) 1.10-104].

Conclusions: Laparoscopic removal of MUS is feasible and effective but carries a risk of worsening SUI.
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http://dx.doi.org/10.1007/s00192-018-3756-6DOI Listing
August 2019

What's New in Epidemiology?

Eur Urol Focus 2018 01 12;4(1):11-13. Epub 2018 Feb 12.

Departments of Urology and Public Health, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

There have been a number of recent advances in the epidemiological study of male lower urinary tract symptoms (LUTS). Here, we have reviewed the most novel and important literature. Studies assessing the risk factors, natural history as well as impact of male LUTS are included, focussing on recent progress in the field.
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http://dx.doi.org/10.1016/j.euf.2018.02.003DOI Listing
January 2018

Metallic Ureteric Stents in Malignant Ureteric Obstruction: A Systematic Review.

Urology 2018 Aug 24;118:12-20. Epub 2018 May 24.

Department of Urology, Imperial College Healthcare NHS Trust, Charing Cross Hospital, London, United Kingdom. Electronic address:

The effectiveness of metallic stents in the management of malignant ureteric obstruction is unclear. This systematic review evaluates the use of 4 commercially available metallic stents (Resonance, Memokath 051, Uventa, and Allium URS). Twenty-one studies met eligibility criteria. Overall success rates ranged from 88% for the Allium stent to 65% for Memokath 051. Resonance demonstrated the lowest migration rate (1%). Uventa had the lowest obstruction rate (6%). Metallic ureteric stents offer a viable alternative in the management of malignant ureteric obstruction. Further high quality studies are required to assess cost effectiveness and refine specific indications based on etiology and level of the ureteric obstruction.
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http://dx.doi.org/10.1016/j.urology.2018.01.019DOI Listing
August 2018

Urinary incontinence in women.

Nat Rev Dis Primers 2017 Nov 16;3:17097. Epub 2017 Nov 16.

This corrects the article DOI: 10.1038/nrdp.2017.42.
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http://dx.doi.org/10.1038/nrdp.2017.97DOI Listing
November 2017

What was hot at ICS 2016?

Neurourol Urodyn 2017 Nov;36(8):2176-2180

Section of Surgical Sciences, Vanderbilt University Medical Centre, Nashville, Tennessee.

The 46th annual conference of the International Continence Society was held in Tokyo, Japan, between September 13th and 16th, 2016. In this article, we present selected highlights of the broad range of excellent research presented by colleagues from around the world from a variety of areas of continence research, from cellular models to population-based epidemiological studies.
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http://dx.doi.org/10.1002/nau.23254DOI Listing
November 2017

Urinary Metabolic Phenotyping of Women with Lower Urinary Tract Symptoms.

J Proteome Res 2017 11 4;16(11):4208-4216. Epub 2017 Oct 4.

Department of Urogynaecology, St. Mary's Hospital, Imperial College Healthcare NHS Trust , London W2 1NY, U.K.

Lower urinary tract symptoms (LUTS), including urinary incontinence, urgency and nocturia, affect approximately half of women worldwide. Current diagnostic methods for LUTS are invasive and costly, while available treatments are limited by side effects leading to poor patient compliance. In this study, we aimed to identify urine metabolic signatures associated with LUTS using proton nuclear magnetic resonance (H NMR) spectroscopy. A total of 214 urine samples were collected from women attending tertiary urogynecology clinics (cases; n = 176) and healthy control women attending general gynecology clinics (n = 36). Despite high variation in the urine metabolome across the cohort, associations between urine metabolic profiles and BMI, parity, overactive bladder syndrome, frequency, straining, and bladder storage were identified using KODAMA (knowledge discovery by accuracy maximization). Four distinct urinary metabotypes were identified, one of which was associated with increased urinary frequency and low BMI. Urine from these patients was characterized by increased levels of isoleucine and decreased levels of hippurate. Our study suggests that metabolic profiling of urine samples from LUTS patients offers the potential to identify differences in underlying etiology, which may permit stratification of patient populations and the design of more personalized treatment strategies.
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http://dx.doi.org/10.1021/acs.jproteome.7b00568DOI Listing
November 2017
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