Extracellular vesicles in urological malignancies

Extracellular vesicles (EVs) are small lipid bound structures released from cells containing bioactive cargoes. Both the type of cargo and amount loaded varies compared to that of the parent cell. The characterisation of EVs in cancers of the male urogenital tract has identified several cargoes with promising diagnostic and disease monitoring potential. EVs released by cancers of the male urogenital tract promote cell-to-cell communication, migration, cancer progression and manipulate the immune system promoting metastasis by evading the immune response. Their use as diagnostic biomarkers represents a new area of screening and disease detection, potentially reducing the need for invasive biopsies. Many validated EV cargoes have been found to have superior sensitivity and specificity than current diagnostic tools currently in use. The use of EVs to improve disease monitoring and develop novel therapeutics will enable clinicians to individualise patient management in the exciting era of personalised medicine

Impact of taxane-based chemotherapeutics on male reproductive function

Men and boys with cancer treated with chemotherapy are known to have reduced fertility following their treatment. This is because some chemotherapy drugs can damage the cells in the testicles that make sperm. This study found there is limited information available on the effect of one group of chemotherapy drugs, called taxanes, on testicular function and fertility. More studies are needed to aid clinicians in advising patients on how this taxane-based chemotherapy may affect their future fertility

The risk of miscarriage following COVID-19 vaccination: a systematic review and meta-analysis

STUDY QUESTION: What is the risk of miscarriage among pregnant women who received any of the COVID-19 vaccines? SUMMARY ANSWER: There is no evidence that COVID-19 vaccines are associated with an increased risk of miscarriage. WHAT IS KNOWN ALREADY: In response to the COVID-19 pandemic, the mass roll-out of vaccines helped to boost herd immunity and reduced hospital admissions, morbidity and mortality. Still, many were concerned about the safety of vaccinesfor pregnancy, which may have limited their uptake among pregnant women and those planning a pregnancy. STUDY DESIGN, SIZE, DURATION: For this systematic review and meta-analysis, we searched MEDLINE, EMBASE and Cochrane CENTRAL from inception until June 2022 using a combination of keywords and MeSH terms. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included observational and interventional studies that enrolled pregnant women and evaluated any of the available COVID-19 vaccines compared to placebo or no vaccination. We primarily reported on miscarriage in addition to ongoing pregnancy and/or live birth. MAIN RESULTS AND THE ROLE OF CHANCE: We included data from 21 studies (5 randomised trials and 16 observational studies) reporting on 149,685 women. The pooled rate of miscarriage among women who received a COVID-19 vaccine was 9% (n = 147,49/123,185, 95%CI 0.05-0.14). Compared to those who received a placebo or no vaccination, women who received a COVID-19 vaccine did not have a higher risk of miscarriage (RR 1.07, 95%CI 0.89-1.28, I2 35.8%) and had comparable rates for ongoing pregnancy or live birth (RR 1.00, 95%CI 0.97-1.03, I2 10.72%). LIMITATIONS, REASONS FOR CAUTION: Our analysis was limited to observational evidence with varied reporting, high heterogeneity and risk of bias across included studies, which may limit the generalisability and confidence in our findings. WIDER IMPLICATIONS OF THE FINDINGS: COVID-19 vaccines are not associated with an increase in the risk of miscarriage or reduced rates of ongoing pregnancy or live birth among women of reproductive age. The current evidence remains limited and larger population studies are needed to further evaluate the effectiveness and safety of COVID-19 in pregnancy. STUDY FUNDING/COMPETING INTEREST: No direct funding was provided to support this work. MPR is funded by the Medical Research Council Centre for Reproductive Heath Grant No: MR/N022556/1. BHA hold a personal development award from the National Institute of Health Research in the UK. All authors declare no conflict of interest. REGISTRATION NUMBER: CRD42021289098

Diagnosis and management of endometrial hyperplasia: a UK National audit of adherence to National Guidance 2012-20

Background: Endometrial hyperplasia (EH) is a precusor lesion for endometrial cancer (EC), the commonest gynaecological malignancy in high-income countries. EH is a proliferation of glandular tissue, classified as either non-atypical endometrial hyperplasia (NEH) or if the cytological features are abnormal, atypical endometrial hyperplasia (AEH). The clinical significance of AEH is that patients face both a high risk of having occult EC and a high risk of progression to EC if untreated. Recommendations on the care of women with EH were introduced by UK-wide guidance (Green-top Guide No.67, 2016). National adherence to guidance is unknown. We aimed to describe the care of patients with EH; to compare the patterns of care for those with EH with national guidance to identify opportunities for quality improvement; and to compare patterns of care prior to and following the introduction of national guidance to understand its impact. Methods and Findings: In this UK-wide patient-level clinical audit, we included 3,307 women who received a new histological diagnosis of EH through a gynaecology service between 1st January 2012 and 30th June 2020. We described first-line management, management at two-years, and surgical characteristics prior to and following national guidance for EH using proportions and 95% confidence intervals and compared process measures between time periods using multilevel Poisson regression. Of the 3,307 patients, 1,570 had non-atypical hyperplasia (NEH) and 1,511 had atypical hyperplasia (AEH) between 2012 and 2019. An additional 85 patients had NEH and 141 had AEH during 2020. Prior to national guidance, 9% (95% CI [6%, 15%]) received no initial treatment for NEH compared with 3% (95% CI [1%, 5%]) post-guidance; 31% (95% CI [26%, 36%]) and 48% (95% CI [43% 53%]) received an intrauterine progestogen, respectively, in the same periods. The predominant management of women with AEH did not differ, with 68% (95% CI [61%, 74%]) and 67% (95 CI [63%, 71%]) receiving first-line hysterectomy, respectively. By two years, follow-up to histological regression without hysterectomy increased from 38% (95% CI [33%, 43%]) to 52% (95% CI [47%, 58%]) for those with NEH (RR 1.38, 95% CI [1.18, 1.63] p<0.001). We observed an increase in the use of total laparoscopic hysterectomy among those with AEH (RR 1.26, 95% CI [1.04, 1.52]). In the later period, 37% (95% CI [29%, 44%]) of women initially diagnosed with AEH who underwent a first-line hysterectomy, received an upgraded diagnosis of EC. Study limitations included retrospective data collection from routine clinical documentation and the inability to comprehensively understand the shared decision-making process where care differed from guidance. Conclusions: The care of patients with EH has changed in accordance with national guidance. More women received first line medical management of NEH and were followed up to histological regression. The follow-up of those with 4 AEH who do not undergo hysterectomy must be improved, given their very high risk of co-existent cancer and high risk of developing cancer

Diagnosis and management of endometrial hyperplasia: A UK national audit of adherence to national guidance 2012-2020

BACKGROUND: Endometrial hyperplasia (EH) is a precusor lesion for endometrial cancer (EC), the commonest gynaecological malignancy in high-income countries. EH is a proliferation of glandular tissue, classified as either non-atypical endometrial hyperplasia (NEH) or, if the cytological features are abnormal, atypical endometrial hyperplasia (AEH). The clinical significance of AEH is that patients face both a high risk of having occult EC and a high risk of progression to EC if untreated. Recommendations on the care of women with EH were introduced by United Kingdom-wide guidance (Green-top Guide No. 67, 2016). National adherence to guidance is unknown. We aimed to describe the care of patients with EH; to compare the patterns of care for those with EH with national guidance to identify opportunities for quality improvement; and to compare patterns of care prior to and following the introduction of national guidance to understand its impact. METHODS AND FINDINGS: In this UK-wide patient-level clinical audit, we included 3,307 women who received a new histological diagnosis of EH through a gynaecology service between 1 January 2012 and 30 June 2020. We described first-line management, management at 2 years, and surgical characteristics prior to and following national guidance for EH using proportions and 95% confidence intervals (CIs) and compared process measures between time periods using multilevel Poisson regression. Of the 3,307 patients, 1,570 had NEH and 1,511 had AEH between 2012 and 2019. An additional 85 patients had NEH and 141 had AEH during 2020. Prior to national guidance, 9% (95% CI [6%, 15%]) received no initial treatment for NEH compared with 3% (95% CI [1%, 5%]) post-guidance; 31% (95% CI [26%, 36%]) and 48% (95% CI [43% 53%]) received an intrauterine progestogen, respectively, in the same periods. The predominant management of women with AEH did not differ, with 68% (95% CI [61%, 74%]) and 67% (95 CI [63%, 71%]) receiving first-line hysterectomy, respectively. By 2 years, follow-up to histological regression without hysterectomy increased from 38% (95% CI [33%, 43%]) to 52% (95% CI [47%, 58%]) for those with NEH (rate ratio (RR) 1.38, 95% CI [1.18, 1.63] p < 0.001). We observed an increase in the use of total laparoscopic hysterectomy among those with AEH (RR 1.26, 95% CI [1.04, 1.52]). In the later period, 37% (95% CI [29%, 44%]) of women initially diagnosed with AEH who underwent a first-line hysterectomy, received an upgraded diagnosis of EC. Study limitations included retrospective data collection from routine clinical documentation and the inability to comprehensively understand the shared decision-making process where care differed from guidance. CONCLUSIONS: The care of patients with EH has changed in accordance with national guidance. More women received first-line medical management of NEH and were followed up to histological regression. The follow-up of those with AEH who do not undergo hysterectomy must be improved, given their very high risk of coexistent cancer and high risk of developing cancer

Diagnosis and Management of Endometrial Hyperplasia: A UK National Audit of Adherence to National Guidance 2012-20

BackgroundEndometrial hyperplasia (EH) is a precusor lesion for endometrial cancer (EC), the commonest gynaecological malignancy in high-income countries. EH is a proliferation of glandular tissue, classified as either non-atypical endometrial hyperplasia (NEH) or, if the cytological features are abnormal, atypical endometrial hyperplasia (AEH). The clinical significance of AEH is that patients face both a high risk of having occult EC and a high risk of progression to EC if untreated. Recommendations on the care of women with EH were introduced by United Kingdom–wide guidance (Green-top Guide No. 67, 2016). National adherence to guidance is unknown.We aimed to describe the care of patients with EH; to compare the patterns of care for those with EH with national guidance to identify opportunities for quality improvement; and to compare patterns of care prior to and following the introduction of national guidance to understand its impact.Methods and findingsIn this UK-wide patient-level clinical audit, we included 3,307 women who received a new histological diagnosis of EH through a gynaecology service between 1 January 2012 and 30 June 2020. We described first-line management, management at 2 years, and surgical characteristics prior to and following national guidance for EH using proportions and 95% confidence intervals (CIs) and compared process measures between time periods using multilevel Poisson regression.Of the 3,307 patients, 1,570 had NEH and 1,511 had AEH between 2012 and 2019. An additional 85 patients had NEH and 141 had AEH during 2020. Prior to national guidance, 9% (95% CI [6%, 15%]) received no initial treatment for NEH compared with 3% (95% CI [1%, 5%]) post-guidance; 31% (95% CI [26%, 36%]) and 48% (95% CI [43% 53%]) received an intrauterine progestogen, respectively, in the same periods. The predominant management of women with AEH did not differ, with 68% (95% CI [61%, 74%]) and 67% (95 CI [63%, 71%]) receiving first-line hysterectomy, respectively. By 2 years, follow-up to histological regression without hysterectomy increased from 38% (95% CI [33%, 43%]) to 52% (95% CI [47%, 58%]) for those with NEH (rate ratio (RR) 1.38, 95% CI [1.18, 1.63] p &lt; 0.001). We observed an increase in the use of total laparoscopic hysterectomy among those with AEH (RR 1.26, 95% CI [1.04, 1.52]). In the later period, 37% (95% CI [29%, 44%]) of women initially diagnosed with AEH who underwent a first-line hysterectomy, received an upgraded diagnosis of EC. Study limitations included retrospective data collection from routine clinical documentation and the inability to comprehensively understand the shared decision-making process where care differed from guidance.ConclusionsThe care of patients with EH has changed in accordance with national guidance. More women received first-line medical management of NEH and were followed up to histological regression. The follow-up of those with AEH who do not undergo hysterectomy must be improved, given their very high risk of coexistent cancer and high risk of developing cancer

Impact of taxane-based chemotherapeutics on male reproductive function

Men and boys with cancer treated with chemotherapy are known to have reduced fertility following their treatment. This is because some chemotherapy drugs can damage the cells in the testicles that make sperm. This study found there is limited information available on the effect of one group of chemotherapy drugs, called taxanes, on testicular function and fertility. More studies are needed to aid clinicians in advising patients on how this taxane-based chemotherapy may affect their future fertility

Efficacy of virtual reality for pain relief in medical procedures: A systematic review and meta-analysis

BackgroundEffective pain control is crucial to optimise the success of medical procedures. Immersive virtual reality (VR) technology could offer an effective non-invasive, non-pharmacological option to distract patients and reduce their experience of pain. We aimed to evaluate the efficacy of Immersive virtual reality (VR) technology in reducing patient’s pain perception during various medical procedures by conducting a systematic review and meta-analysis.MethodsWe searched MEDLINE, EMBASE, CENTRAL, CINAHL, and SIGLE until December 2022 for all randomised clinical trials (RCT) evaluating any type of VR in patients undergoing any medical procedure. We conducted a random effect meta-analysis summarising standardised mean differences (SMD) with 95% confidence intervals (CI). We evaluated heterogeneity using I 2 and explored it using subgroup and meta-regression analyses.ResultsIn total, we included 92 RCTs (n = 7133 participants). There was a significant reduction in pain scores with VR across all medical procedures (n = 83, SMD − 0.78, 95% CI − 1.00 to − 0.57, I 2 = 93%, p = &lt; 0.01). Subgroup analysis showed varied reduction in pain scores across trial designs [crossover (n = 13, SMD − 0.86, 95% CI − 1.23 to − 0.49, I 2 = 72%, p = &lt; 0.01) vs parallel RCTs (n = 70, SMD − 0.77, 95% CI − 1.01 to − 0.52, I 2 = 90%, p = &lt; 0.01)]; participant age groups [paediatric (n = 43, SMD − 0.91, 95% CI − 1.26 to − 0.56, I 2 = 87%, p = &lt; 0.01) vs adults (n = 40, SMD − 0.66, 95% CI − 0.94 to − 0.39, I 2 = 89%, p = &lt; 0.01)] or procedures [venepuncture (n = 32, SMD − 0.99, 95% CI − 1.52 to − 0.46, I 2 = 90%, p = &lt; 0.01) vs childbirth (n = 7, SMD − 0.99, 95% CI − 1.59 to − 0.38, I 2 = 88%, p = &lt; 0.01) vs minimally invasive medical procedures (n = 25, SMD − 0.51, 95% CI − 0.79 to − 0.23, I 2 = 85%, p = &lt; 0.01) vs dressing changes in burn patients (n = 19, SMD − 0.8, 95% CI − 1.16 to − 0.45, I 2 = 87%, p = &lt; 0.01)]. We explored heterogeneity using meta-regression which showed no significant impact of different covariates including crossover trials (p = 0.53), minimally invasive procedures (p = 0.37), and among paediatric participants (p = 0.27). Cumulative meta-analysis showed no change in overall effect estimates with the additional RCTs since 2018.ConclusionsImmersive VR technology offers effective pain control across various medical procedures, albeit statistical heterogeneity. Further research is needed to inform the safe adoption of this technology across different medical disciplines

Intralipid infusion at time of embryo transfer in women with history of recurrent implantation failure : a systematic review and meta-analysis

Aim: Recurrent implantation failure (RIF) affects 10% of couples undergoing assisted conception, often due to poor endometrial receptivity. We conducted a systematic review and meta‐analysis to evaluate the effectiveness of Intra‐venous intralipid (IVI) in improving pregnancy rates in women with history of RIF using. Methods: We searched MEDLINE, EMBASE, and CENTRAL for any randomized trials evaluating the use of IVI at the time of embryo transfer in women undergoing assisted conception until September 2020. We extracted data in duplicate and assessed risk of bias using the Cochrane Risk of Bias tools. We meta‐analyzed data using a random effect model. Results: We included five randomized trials reporting on 843 women with an overall moderate risk of bias. All trials used 20% IVI solution at the time of embryo transfer compared to normal saline infusion or no intervention (routine care). The IVI group had a higher chance of clinical pregnancy (172 vs 119, risk ratio [RR] 1.55, 95% confidence interval [CI] 1.16–2.07, I2 44.2%) and live birth (132 vs 73, RR 1.83, 95% CI 1.42–2.35, I2 0%) post treatment compared to no intervention. Our findings are limited by the small sample size and the variations in treatment protocols and population characteristics. Conclusion: There is limited evidence to support the use of IVI at the time of embryo transfer in women with the history of RIF. More research is needed before adopting it in clinical practice