In vitro biomechanical properties of porcine perineal tissues to better understand human perineal tears during delivery.

INTRODUCTION: Data concerning the mechanical properties of the perineum during delivery are very limited. In vivo experiments raise ethical issues. The aim of the study was to describe some of the biomechanical properties of each perineal tissue layer collected from sows in order to better understand perineal tears during childbirth. MATERIAL AND METHODS: Samples of each perineal tissue layer were obtained from the skin, the vagina, the external anal sphincter (EAS), the internal anal sphincter (IAS), and the anal mucosa of fresh dead sows. They were tested in quasi-static uniaxial tension using the testing machine Mach-1®. Tests were performed at a displacement velocity of 0.1 mm·s-1. Stress-strain curves of each perineal tissue layer before the first damage for each sow were obtained and modeled using a hyperelastic Yeoh model described by three coefficients: C1, C2, and C3. Pearson correlation coefficients were calculated to measure the correlation between the C1 hyperelastic coefficient and the duration between the first microfailure and the complete rupture for each perineal tissue layer. Pearson correlation was computed between C1 and the number of microfailures before complete rupture for each tissue. RESULTS: Ten samples of each perineal tissue layer were analyzed. Mean values of C1 and corresponding standard deviations were 46 ± 15, 165 ± 60, 27 ± 10, 19 ± 13, 145 ± 28 kPa for the perineal skin, the vagina, the EAS, the IAS, and the anal mucosa, respectively. According to this same sample order, the first microfailure in the population of 10 sows appeared at an average of 54%, 27%, 70%, 131%, and 22% of strain. A correlation was found between C1 hyperelastic coefficient and the duration between the first microfailure and the complete rupture (r = 0.7, p = 0.02) or the number of microfailures before complete rupture only for the vagina (r = 0.7, p = 0.02). CONCLUSIONS: In this population of fresh dead sow's perineum, the vagina and the anal mucosa were the stiffest tissues. The IAS and EAS were more extensible and less stiff. A significantly positive correlation was found between C1 and the duration between the first microfailure and the complete rupture of the vagina, and the duration between the first microfailure and the complete rupture of the vagina.

Performance of a Region of Interest-based Algorithm in Diagnosing International Society of Urological Pathology Grade Group ≥2 Prostate Cancer on the MRI-FIRST Database-CAD-FIRST Study.

BACKGROUND AND OBJECTIVE: Prostate multiparametric magnetic resonance imaging (MRI) shows high sensitivity for International Society of Urological Pathology grade group (GG) ≥2 cancers. Many artificial intelligence algorithms have shown promising results in diagnosing clinically significant prostate cancer on MRI. To assess a region-of-interest-based machine-learning algorithm aimed at characterising GG ≥2 prostate cancer on multiparametric MRI. METHODS: The lesions targeted at biopsy in the MRI-FIRST dataset were retrospectively delineated and assessed using a previously developed algorithm. The Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2) score assigned prospectively before biopsy and the algorithm score calculated retrospectively in the regions of interest were compared for diagnosing GG ≥2 cancer, using the areas under the curve (AUCs), and sensitivities and specificities calculated with predefined thresholds (PIRADSv2 scores ≥3 and ≥4; algorithm scores yielding 90% sensitivity in the training database). Ten predefined biopsy strategies were assessed retrospectively. KEY FINDINGS AND LIMITATIONS: After excluding 19 patients, we analysed 232 patients imaged on 16 different scanners; 85 had GG ≥2 cancer at biopsy. At patient level, AUCs of the algorithm and PI-RADSv2 were 77% (95% confidence interval [CI]: 70-82) and 80% (CI: 74-85; p = 0.36), respectively. The algorithm's sensitivity and specificity were 86% (CI: 76-93) and 65% (CI: 54-73), respectively. PI-RADSv2 sensitivities and specificities were 95% (CI: 89-100) and 38% (CI: 26-47), and 89% (CI: 79-96) and 47% (CI: 35-57) for thresholds of ≥3 and ≥4, respectively. Using the PI-RADSv2 score to trigger a biopsy would have avoided 26-34% of biopsies while missing 5-11% of GG ≥2 cancers. Combining prostate-specific antigen density, the PI-RADSv2 and algorithm's scores would have avoided 44-47% of biopsies while missing 6-9% of GG ≥2 cancers. Limitations include the retrospective nature of the study and a lack of PI-RADS version 2.1 assessment. CONCLUSIONS AND CLINICAL IMPLICATIONS: The algorithm provided robust results in the multicentre multiscanner MRI-FIRST database and could help select patients for biopsy. PATIENT SUMMARY: An artificial intelligence-based algorithm aimed at diagnosing aggressive cancers on prostate magnetic resonance imaging showed results similar to expert human assessment in a prospectively acquired multicentre test database.

Prognostic Impact of Prostate-Specific Antigen at 6 Months After Radiotherapy in Localized Prostate Cancer: An Individual Patient Data Analysis of Randomized Trials.

PURPOSE: We sought to evaluate the prognostic impact of prostate-specific antigen (PSA) at 6 months after completion of radiotherapy (RT) in patients treated with RT alone, RT plus short-term (st; 3-6 months), and RT plus long-term (lt; 24-36 months) androgen-deprivation therapy (ADT). PATIENTS AND METHODS: Individual patient data were obtained from 16 randomized trials evaluating RT ± ADT for localized prostate cancer (PCa) between 1987 and 2011. The lowest PSA recorded within 6 months after RT completion was identified and categorized as < or ≥0.1 ng/mL. The primary outcomes were metastasis-free survival (MFS), PCa-specific mortality (PCSM), and overall survival (OS), from 12 months after random assignment. RESULTS: Ninety-eight percent (n = 2,339/2,376) of patients allocated to RT alone, 84% (n = 4,756/5,658) allocated to RT + stADT, and 77% (n = 1,258/1,626) allocated to RT + ltADT had PSA ≥0.1 ng/mL within 6 months after completing RT. PSA ≥0.1 ng/mL was associated with lower MFS and OS and higher PCSM among patients allocated to RT ± ADT (RT - MFS: hazard ratio [HR], 2.24 [95% CI, 1.21 to 4.16]; PCSM: subdistribution hazard ratio [sHR], 1.82 [0.51 to 6.49]; OS: HR, 1.72 [0.97 to 3.05]; RT + stADT - MFS: HR, 1.27 [1.12 to 1.44]; PCSM: sHR, 2.10 [1.52 to 2.92]; OS: HR, 1.26 [1.11 to 1.44]; RT + ltADT - MFS: HR, 1.58 [1.27 to 1.96]; PCSM: sHR, 1.97 [1.11 to 3.49]; OS: HR, 1.59 [1.27 to 1.99]). Five-year MFS rates among patients allocated to RT, RT + stADT, and RT + ltADT were 91% versus 79%, 83% versus 76%, and 87% versus 74%, respectively, based on PSA < or ≥0.1 ng/mL. CONCLUSION: PSA ≥0.1 ng/mL within 6 months after RT completion was prognostic for lt outcomes in patients treated with RT ± ADT for localized PCa. This can be used to counsel patients treated with RT ± ADT and in guiding clinical trial design evaluating novel systemic therapies with RT + ADT as well as (de)intensification strategies.

The OdonAssist inflatable device for assisted vaginal birth-the ASSIST II study (United Kingdom).

BACKGROUND: Decreasing rates of assisted vaginal birth have been paralleled with increasing rates of cesarean deliveries over the last 40 years. The OdonAssist is a novel device for assisted vaginal birth. Iterative changes to clinical parameters, device design, and technique have been made to improve device efficacy and usability. OBJECTIVE: This study aimed to determine if the feasibility, safety, and efficacy of the OdonAssist device were sufficient to justify conducting a future randomized controlled trial. STUDY DESIGN: An open-label nonrandomized study of 104 participants having a clinically indicated assisted vaginal birth using the OdonAssist was undertaken at Southmead Hospital, Bristol, United Kingdom. Data were also collected from participants who consented to participate in the study but for whom trained OdonAssist operators were not available, providing a nested cohort. The primary clinical outcome was the proportion of births successfully expedited with the OdonAssist. Secondary outcomes included clinical, patient-reported, operator-reported, device and health care utilization. Neonatal outcome data were reviewed at day 28, and maternal outcomes were investigated up to day 90. Given that the number of successful OdonAssist births was ≥61 out of 104, the hypothesis of a poor rate of 50% was rejected in favor of a good rate of ≥65%. RESULTS: Between August 2019 and June 2021, 941 (64%) of the 1471 approached, eligible participants consented to participate. Of these, 104 received the OdonAssist intervention. Birth was assisted in all cephalic vertex fetal positions, at all stations ≥1 cm below the ischial spines (with or without regional analgesia). The OdonAssist was effective in 69 of the 104 (66%) cases, consistent with the hypothesis of a good efficacy rate. There were no serious device-related maternal or neonatal adverse reactions, and there were no serious adverse device effects. Only 4% of neonatal soft tissue bruising in the successful OdonAssist group was considered device-related, as opposed to 20% and 23% in the unsuccessful OdonAssist group and the nested cohort, respectively. Participants reported high birth perception scores. All practitioners found the device use to be straightforward. CONCLUSION: Recruitment to an interventional study of a new device for assisted vaginal birth is feasible; 64% of eligible participants were willing to participate. The success rate of the OdonAssist was comparable to that of the Kiwi OmniCup when introduced in the same unit in 2002, meeting the threshold for a randomized controlled trial to compare the OdonAssist with current standard practice. There were no disadvantages of study participation in terms of maternal and neonatal outcomes. There were potential advantages of using the OdonAssist, particularly reduced neonatal soft tissue injury. The same application technique is used for all fetal positions, with all operators deeming the device straightforward to use. This study provides important data to inform future study design.

Safety and efficacy of the OdonAssist inflatable device for assisted vaginal birth: the BESANCON ASSIST study.

BACKGROUND: The first feasibility study of the OdonAssist inflatable device for use in clinically indicated assisted vaginal birth reported a success rate of 48% with no significant safety concerns. Additional studies exploring the device performance in other clinical settings are warranted before definitive conclusions can be drawn about its safety and efficacy in current practice. OBJECTIVE: This study aimed to investigate the safety and efficacy of the OdonAssist before conducting a randomized controlled trial. STUDY DESIGN: This was an open-label, nonrandomized study of 104 women with a clinically indicated assisted vaginal birth using the OdonAssist at the Besancon University Hospital, France. Data, including those of a nested cohort group of women who had an assisted vaginal birth using vacuum or spatulas because a trained OdonAssist device operator was not available at the time of delivery, were collected. The primary outcome measure was the proportion of successful assisted vaginal births using the OdonAssist. Neonatal outcome data were reviewed at days 1 and 28, and maternal outcomes were investigated up to day 90. RESULTS: Between December 2019 and May 2021, 2191 pregnant women were approached, and 83% (1636/1973) of them consented to participate in the study. Among them, 10.7% (176/1636) required an assisted vaginal birth owing to a vertex presentation at +1 and below. The OdonAssist was used in 59% of births (104/176), and 41.1% (72/176) of the participants were included in the nested cohort group. The rate of successful assisted vaginal births using the OdonAssist was 88.5% (92/104). No emergency cesarean deliveries were performed in the OdonAssist group. There were no serious adverse maternal or neonatal reactions related to the use of the device. The rate of third- and fourth-degree perineal tears with the OdonAssist was 3.8% (4/104). The maternal perception ratings of the birth experience with the OdonAssist (collected on days 1, 7, and 28 using a 15-point scale) were high. In addition, the operators reported a positive perception of the device, with ease of use across the different steps of the procedure. One single technique was used for all vertex fetal head positions. CONCLUSION: The OdonAssist is a safe and effective alternative to other current devices for assisted vaginal births. The high acceptance rate (83%) among pregnant women and the high rate of successful assisted vaginal births using the OdonAssist confirm the feasibility of a future randomized controlled trial.

Analysis of the transplacental transmission of SARS CoV-2 virus and antibody transfer according to the gestational age at maternal infection.

To quantify transplacental transmission of SARS-CoV-2 virus and antibody transfer in pregnant women and their newborns according to the gestational age at maternal infection. A prospective observational multicenter study including pregnant women with a positive RT-PCR or a positive serology for SARS-CoV-2 and compatible symptoms, from April to December 2020, in 11 French maternities. The study was designed to obtain a systematic collection of mother-infant dyad's samples at birth. SARS-CoV-2 viral load was measured by RT-PCR. IgG and IgM antibodies against the SARS-CoV-2 spike protein were measured by enzyme-linked immunosorbent assay. Antibody concentrations and transplacental transfer ratios were analyzed according to the gestational age at maternal infection. The primary outcome was the rate of SARS CoV-2 materno-fetal transmission at birth. The secondary outcome was the quantification of materno-fetal antibody transfer. Maternal and neonatal outcomes at birth were additionally assessed. Among 165 dyads enrolled, one congenital infection was confirmed {n = 1 (0.63%) IC95% [0.02%; 3.48%]}. The average placental IgG antibody transfer ratio was 1.27 (IC 95% [0.69-2.89]). The transfer ratio increased with increasing time between the onset of maternal infection and delivery (P Value = 0.0001). Maternal and neonatal outcomes were reassuring. We confirmed the very low rate of SARS-CoV-2 transplacental transmission (< 1%). Maternal antibody transfer to the fetus was more efficient when the infection occurred during the first and second trimester of pregnancy.

Updating of pelvimetry standards in modern obstetrics.

Clinical value of pelvimetry in modern obstetrics practices has never been established and normal values are set since the middle of the twentieth century. The aim of this study was to describe current dimensions of pelvis in a female French Caucasian population. A retrospective, bi-centric observational study was conducted from August 2013 to August 2019 in two French departments of Obstetrics. We included all Caucasian women who had a computed tomography pelvimetry during pregnancy. The primary outcome was the values of the obstetric transverse diameter, obstetric conjugate diameter and bispinous diameter. Five hundred and fifty-one CT pelvimetries were analyzed. The median Obstetric Transverse Diameter (OTD) was 12.41 cm and the 3rd percentile was 11 cm. The median Obstetric Conjugate Diameter (OCD) was 12.2 cm and the 3rd percentile was 10.5 cm. The median Bispinous Diameter (BSD) in our data collection was 10.9 cm and the 3rd percentile was 9.3 cm. A significant correlation coefficient between women's height and OTD, OCD and BSD was found. In our study, the OCD and the BSD have not evolved since the middle of the twentieth century. The obstetric transverse diameter was smaller than the standard currently used.

Clinical Characterization of Patients Diagnosed with Prostate Cancer and Undergoing Conservative Management: A PIONEER Analysis Based on Big Data.

BACKGROUND: Conservative management is an option for prostate cancer (PCa) patients either with the objective of delaying or even avoiding curative therapy, or to wait until palliative treatment is needed. PIONEER, funded by the European Commission Innovative Medicines Initiative, aims at improving PCa care across Europe through the application of big data analytics. OBJECTIVE: To describe the clinical characteristics and long-term outcomes of PCa patients on conservative management by using an international large network of real-world data. DESIGN, SETTING, AND PARTICIPANTS: From an initial cohort of >100 000 000 adult individuals included in eight databases evaluated during a virtual study-a-thon hosted by PIONEER, we identified newly diagnosed PCa cases (n = 527 311). Among those, we selected patients who did not receive curative or palliative treatment within 6 mo from diagnosis (n = 123 146). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patient and disease characteristics were reported. The number of patients who experienced the main study outcomes was quantified for each stratum and the overall cohort. Kaplan-Meier analyses were used to estimate the distribution of time to event data. RESULTS AND LIMITATIONS: The most common comorbidities were hypertension (35-73%), obesity (9.2-54%), and type 2 diabetes (11-28%). The rate of PCa-related symptomatic progression ranged between 2.6% and 6.2%. Hospitalization (12-25%) and emergency department visits (10-14%) were common events during the 1st year of follow-up. The probability of being free from both palliative and curative treatments decreased during follow-up. Limitations include a lack of information on patients and disease characteristics and on treatment intent. CONCLUSIONS: Our results allow us to better understand the current landscape of patients with PCa managed with conservative treatment. PIONEER offers a unique opportunity to characterize the baseline features and outcomes of PCa patients managed conservatively using real-world data. PATIENT SUMMARY: Up to 25% of men with prostate cancer (PCa) managed conservatively experienced hospitalization and emergency department visits within the 1st year after diagnosis; 6% experienced PCa-related symptoms. The probability of receiving therapies for PCa decreased according to time elapsed after the diagnosis.

Research protocol to identify progression and death amongst patients with metastatic hormone-sensitive prostate cancer treated with available treatments: PIONEER IMI's "big data for better outcomes" program.

Androgen deprivation therapy-based with or without first-generation anti-androgens, was the standard of care for patients with metastatic hormone-sensitive prostate cancer (mHSPC) for decades. However, the development of docetaxel chemotherapy and new androgen receptor-targeted agents, abiraterone acetate and prednisolone, apalutamide , enzalutamide and darolutamide (in combination with docetaxel chemotherapy) has proven that combination of treatments is more effective. Recently, intensification therapy, so-called "triplets", have emerged in the armamentarium of mHSPC treatment. Metastatic disease is a clinical state that remains poorly understood. The optimal diagnostic and management of patients with mHSPC are changing thanks to the development of new imaging techniques and therapies. The primary objective of this study is to develop and validate a predictive model for the occurrence of symptomatic progression, initiation of new treatments and death amongst patients with mHSPC treated with one of the approved treatment plans, on characteristics present at admission.

Influence of in utero fetal death on perineal tears in vaginal deliveries.

The aim of this work was to evaluate and compare the incidence of perineal tears and Obstetrical anal sphincter injuries (OASIS) after vaginal delivery following a in utero fetal death (IUFD) compared with those with a live-birth. We conducted a single-center, retrospective cohort study using a database of all women who underwent a spontaneous vaginal delivery in the level III maternity ward. Exclusion criteria were breech presentation, cesarean section birth, instrumental delivery, multiple pregnancy, delivery before 24 + 6 weeks of gestation (WG) and termination of pregnancy for medical reasons. Women from the database were divided into two groups: an "in utero fetal death" (IUFD) group and a control group. Women were included in the IUFD group if they had a spontaneous vaginal delivery following a fetal demise after 24 + 6 WG in cephalic presentation between January 2006 and June 2020. Women in the "control" group were selected from the same database and were included if they underwent a spontaneous vaginal delivery of a live fetus in cephalic presentation, after 24 + 6 WG, during the same period. Each woman in the "IUFD" group was matched to two women (ratio 1:2) in the control group for parity, maternal age, body mass index, gestation and birth weight. The primary outcome was the presence of a sutured or unsutured perineal tear. During the study period, 31,208 patients delivered at a level III maternity hospital. Among them, 215 and 430 women were included in the IUFD group and the control group respectively. The two groups were comparable for all demographic and clinical characteristics except for an epidural analgesia (92% versus 70% in the control group, p < 0.01) and labor induction (86% versus 17% in the control group, p < 0.01). The incidence of any perineal tears was 13% (28/15) in the IUFD group versus 16% (70/430) in the control group. Relative risk of any perineal tears was non significative (RR = 0.8 IC95% [0.5-1.2]). The incidence of first-degree perineal tears was 10% in the IUFD group and 11% in the control group. The incidence of second-degree perineal tears was 18% in the IUFD group and 28% in the control group. Relative risk of first-degree perineal tears (RR = 0.88 95% CI [0.5-1.4]) and second-degree tears (RR = 0.51 95% CI [0.2-1.4]) were non significative. No obstetrical anal sphincter injury was found in either group. Vaginal delivery following a fetal demise did not appear to be either a risk factor or a protective factor for perineal tears. But there as a trend toward a lower incidence of second degree perineal tears in this context.

Management of patients with advanced prostate cancer-metastatic and/or castration-resistant prostate cancer: Report of the Advanced Prostate Cancer Consensus Conference (APCCC) 2022.

BACKGROUND: Innovations in imaging and molecular characterisation together with novel treatment options have improved outcomes in advanced prostate cancer. However, we still lack high-level evidence in many areas relevant to making management decisions in daily clinical practise. The 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) addressed some questions in these areas to supplement guidelines that mostly are based on level 1 evidence. OBJECTIVE: To present the voting results of the APCCC 2022. DESIGN, SETTING, AND PARTICIPANTS: The experts voted on controversial questions where high-level evidence is mostly lacking: locally advanced prostate cancer; biochemical recurrence after local treatment; metastatic hormone-sensitive, non-metastatic, and metastatic castration-resistant prostate cancer; oligometastatic prostate cancer; and managing side effects of hormonal therapy. A panel of 105 international prostate cancer experts voted on the consensus questions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The panel voted on 198 pre-defined questions, which were developed by 117 voting and non-voting panel members prior to the conference following a modified Delphi process. A total of 116 questions on metastatic and/or castration-resistant prostate cancer are discussed in this manuscript. In 2022, the voting was done by a web-based survey because of COVID-19 restrictions. RESULTS AND LIMITATIONS: The voting reflects the expert opinion of these panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results are reported in the supplementary material. We report here on topics in metastatic, hormone-sensitive prostate cancer (mHSPC), non-metastatic, castration-resistant prostate cancer (nmCRPC), metastatic castration-resistant prostate cancer (mCRPC), and oligometastatic and oligoprogressive prostate cancer. CONCLUSIONS: These voting results in four specific areas from a panel of experts in advanced prostate cancer can help clinicians and patients navigate controversial areas of management for which high-level evidence is scant or conflicting and can help research funders and policy makers identify information gaps and consider what areas to explore further. However, diagnostic and treatment decisions always have to be individualised based on patient characteristics, including the extent and location of disease, prior treatment(s), co-morbidities, patient preferences, and treatment recommendations and should also incorporate current and emerging clinical evidence and logistic and economic factors. Enrolment in clinical trials is strongly encouraged. Importantly, APCCC 2022 once again identified important gaps where there is non-consensus and that merit evaluation in specifically designed trials. PATIENT SUMMARY: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with healthcare providers worldwide. At each APCCC, an expert panel votes on pre-defined questions that target the most clinically relevant areas of advanced prostate cancer treatment for which there are gaps in knowledge. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients and their relatives as part of shared and multidisciplinary decision-making. This report focuses on the advanced setting, covering metastatic hormone-sensitive prostate cancer and both non-metastatic and metastatic castration-resistant prostate cancer. TWITTER SUMMARY: Report of the results of APCCC 2022 for the following topics: mHSPC, nmCRPC, mCRPC, and oligometastatic prostate cancer. TAKE-HOME MESSAGE: At APCCC 2022, clinically important questions in the management of advanced prostate cancer management were identified and discussed, and experts voted on pre-defined consensus questions. The report of the results for metastatic and/or castration-resistant prostate cancer is summarised here.

Impact of Epithelial Histological Types, Subtypes, and Growth Patterns on Oncological Outcomes for Patients with Nonmetastatic Prostate Cancer Treated with Curative Intent: A Systematic Review.

CONTEXT: The optimal management for men with prostate cancer (PCa) with unconventional histology (UH) is unknown. The outcome for these cancers might be worse than for conventional PCa and so different approaches may be needed. OBJECTIVE: To compare oncological outcomes for conventional and UH PCa in men with localized disease treated with curative intent. EVIDENCE ACQUISITION: A systematic review adhering to the Referred Reporting Items for Systematic Reviews and Meta-Analyses was prospectively registered on PROSPERO (CRD42022296013) was performed in July 2021. EVIDENCE SYNTHESIS: We screened 3651 manuscripts and identified 46 eligible studies (reporting on 1 871 814 men with conventional PCa and 6929 men with 10 different PCa UHs). Extraprostatic extension and lymph node metastases, but not positive margin rates, were more common with UH PCa than with conventional tumors. PCa cases with cribriform pattern, intraductal carcinoma, or ductal adenocarcinoma had higher rates of biochemical recurrence and metastases after radical prostatectomy than for conventional PCa cases. Lower cancer-specific survival rates were observed for mixed cribriform/intraductal and cribriform PCa. By contrast, pathological findings and oncological outcomes for mucinous and prostatic intraepithelial neoplasia (PIN)-like PCa were similar to those for conventional PCa. Limitations of this review include low-quality studies, a risk of reporting bias, and a scarcity of studies that included radiotherapy. CONCLUSIONS: Intraductal, cribriform, and ductal UHs may have worse oncological outcomes than for conventional and mucinous or PIN-like PCa. Alternative treatment approaches need to be evaluated in men with these cancers. PATIENT SUMMARY: We reviewed the literature to explore whether prostate cancers with unconventional growth patterns behave differently to conventional prostate cancers. We found that some unconventional growth patterns have worse outcomes, so we need to investigate if they need different treatments. Urologists should be aware of these growth patterns and their clinical impact.

ESTRO-ACROP recommendations for evidence-based use of androgen deprivation therapy in combination with external-beam radiotherapy in prostate cancer.

BACKGROUND AND PURPOSE: There is no consensus concerning the appropriate use of androgen deprivation therapy (ADT) during primary and postoperative external-beam radiotherapy (EBRT) in the management of prostate cancer (PCa). Thus, the European Society for Radiotherapy and Oncology (ESTRO) Advisory Committee for Radiation Oncology Practice (ACROP) guidelines seeks to present current recommendations for the clinical use of ADT in the various indications of EBRT. MATERIAL AND METHODS: A literature search was conducted in MEDLINE PubMed that evaluated EBRT and ADT in prostate cancer. The search focused on randomized, Phase II and III trials published in English from January 2000 to May 2022. In case topics were addressed in the absence of Phase II or III trials, recommendations were labelled accordingly based on the limited body of evidence. Localized PCa was classified according to D'Amico et al. classification in low-, intermediate and high risk PCa. The ACROP clinical committee identified 13 European experts who discussed and analyzed the body of evidence concerning the use of ADT with EBRT for prostate cancer. RESULTS: Key issues were identified and are discussed: It was concluded that no additional ADT is recommended for low-risk prostate cancer patients, whereas for intermediate- and high-risk patients four to six months and two to three years of ADT are recommended. Likewise, patients with locally advanced prostate cancer are recommended to receive ADT for two to three years and when ≥ 2 high-risk factors (cT3-4, ISUP grade ≥ 4 or PSA ≥ 40 ng/ml) or cN1 is present ADT for three years plus additional Abiraterone for two years is recommended. For postoperative patients no ADT is recommended for adjuvant EBRT in pN0 patients whereas for pN1 patients adjuvant EBRT with long-term ADT is performed for at least 24 to 36 months. In the setting of salvage EBRT ADT is performed in biochemically persistent PCa patients with no evidence of metastatic disease. Long-term ADT (24 months) is recommended in pN0 patients with high risk of further progression (PSA ≥ 0.7 ng/ml and ISUP grade group ≥ 4) and a life expectancy of over ten years, whereas short-term ADT (6 months) is recommended in pN0 patients with lower risk profile (PSA < 0.7 ng/ml and ISUP grade group 4). Patients considered for ultra-hypofractionated EBRT as well as patients with image based local recurrence within the prostatic fossa or lymph node recurrence should participate in appropriate clinical trials evaluating the role of additional ADT. CONCLUSION: These ESTRO-ACROP recommendations are evidence-based and relevant to the use of ADT in combination with EBRT in PCa for the most common clinical settings.

Systematic Biopsies as a Complement to Magnetic Resonance Imaging-targeted Biopsies: "To Be or Not To Be"?

In light of recent prostate cancer screening programme proposed by the European Association of Urology, there is an urgent need to optimise detection of clinically significant cancer while minimising overdiagnosis. This may be achieved by omitting systematic biopsies while ensuring quality control for diagnostic magnetic resonance imaging and targeted biopsies.

Mapping European Association of Urology Guideline Practice Across Europe: An Audit of Androgen Deprivation Therapy Use Before Prostate Cancer Surgery in 6598 Cases in 187 Hospitals Across 31 European Countries.

BACKGROUND: Evidence-practice gaps exist in urology. We previously surveyed European Association of Urology (EAU) guidelines for strong recommendations underpinned by high-certainty evidence that impact patient experience for which practice variations were suspected. The recommendation "Do not offer neoadjuvant androgen deprivation therapy (ADT) before surgery for patients with prostate cancer" was prioritised for further investigation. ADT before surgery is neither clinically effective nor cost effective and has serious side effects. The first step in improving implementation problems is to understand their extent. A clear picture of practice regarding ADT before surgery across Europe is not available. OBJECTIVE: To assess current ADT use before prostate cancer surgery in Europe. DESIGN, SETTING, AND PARTICIPANTS: This was an observational cross-sectional study. We retrospectively audited recent ADT practices in a multicentre international setting. We used nonprobability purposive sampling, aiming for breadth in terms of low- versus high-volume, academic, versus community and public versus private centres. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Our primary outcome was adherence to the ADT recommendation. Descriptive statistics and a multilevel model were used to investigate differences between countries across different factors (volume, centre type, and funding type). Subgroup analyses were performed for patients with low, intermediate, and high risk, and for those with locally advanced prostate cancer. We also collected reasons for nonadherence. RESULTS AND LIMITATIONS: We included 6598 patients with prostate cancer from 187 hospitals in 31 countries from January 1, 2017 to May 1, 2020. Overall, nonadherence was 2%, (range 0-32%). Most of the variability was found in the high-risk subgroup, for which nonadherence was 4% (range 0-43%). Reasons for nonadherence included attempts to improve oncological outcomes or preoperative tumour parameters; attempts to control the cancer because of long waiting lists; and patient preference (changing one's mind from radiotherapy to surgery after neoadjuvant ADT had commenced or feeling that the side effects were intolerable). Although we purposively sampled for variety within countries (public/private, academic/community, high/low-volume), a selection bias toward centres with awareness of guidelines is possible, so adherence rates may be overestimated. CONCLUSIONS: EAU guidelines recommend against ADT use before prostate cancer surgery, yet some guideline-discordant ADT use remains at the cost of patient experience and an additional payer and provider burden. Strategies towards discontinuation of inappropriate preoperative ADT use should be pursued. PATIENT SUMMARY: Androgen deprivation therapy (ADT) is sometimes used in men with prostate cancer who will not benefit from it. ADT causes side effects such as weight gain and emotional changes and increases the risk of cardiovascular disease, diabetes, and osteoporosis. Guidelines strongly recommend that men opting for surgery should not receive ADT, but it is unclear how well the guidance is followed. We asked urologists across Europe how patients in their institutions were treated over the past few years. Most do not use ADT before surgery, but this still happens in some places. More research is needed to help doctors to stop using ADT in patients who will not benefit from it.

Maternal and perinatal outcomes following pre-Delta, Delta, and Omicron SARS-CoV-2 variants infection among unvaccinated pregnant women in France and Switzerland: a prospective cohort study using the COVI-PREG registry.

Background: SARS-CoV-2 positive pregnant women are at higher risk of adverse outcomes, but little evidence is available on how variants impact that risk. We aim to evaluate maternal and perinatal outcomes among unvaccinated pregnant women that tested positive for SARS-CoV-2, stratified by pre-Delta, Delta, and Omicron periods. Methods: This prospective study enrolled women from March 2020 to September 2022. Exposure to the different SARS-CoV-2 variants was defined by their periods of predominance. The primary outcome was severe maternal adverse outcome defined as either intensive care unit admission, acute respiratory distress syndrome, advanced oxygen supplementation, or maternal death. The secondary outcomes were preterm birth and other perinatal outcomes. Findings: Overall, 1402, 262, and 391 SARS-CoV-2 positive pregnant women were enrolled during the pre-Delta, Delta, and Omicron periods respectively. Severe maternal adverse outcome was reported in 3.4% (n = 947/1402; 95% confidence intervals (95%CI) 2.5-4.5), 6.5% (n = 7/262; 95%CI 3.8-10.2), and 1.0% (n = 4/391; 95%CI 0.3-2.6) of women during the pre-Delta, Delta, and Omicron periods. The risk of severe maternal adverse outcome was higher during the Delta vs pre-Delta period (adjusted risk ratio (aRR) = 1.8; 95%CI 1.1-3.2) and lower during the Omicron vs pre-Delta period (aRR = 0.3; 95%CI, 0.1-0.8). The risks of hospitalization for COVID-19 were 12.6% (n = 176/1402; 95%CI 10.9-14.4), 17.2% (n = 45/262; 95%CI 12.8-22.3), and 12.5% (n = 49/391; 95%CI 9.4-16.2), during the pre-Delta, Delta, and Omicron period, respectively. Pregnancy complications occurred after SARS-CoV-2 exposure in 30.0% (n = 363/1212; 95%CI 27.4-32.6), 35.2% (n = 83/236; 95%CI 29.1-41.6), and 30.3% (n = 105/347; 95%CI 25.5-35.4) of patients during the pre-Delta, Delta, and Omicron periods, respectively. Stillbirths were reported in 0.5% (n = 6/1159; 95%CI 0.2-1.1), 2.8% (n = 6/210; 95%CI 1.0-6.0), and 0.9% (n = 2/213; 95%CI 0.1-3.4) or patients during the pre-Delta, Delta, and Omicron periods respectively. Interpretation: The Delta period was associated with a higher risk of severe maternal adverse outcome and the Omicron period with a lower risk of severe adverse outcome compared to pre-Delta era. The reported risk of hospitalization was high during the Omicron period and should not be trivialized. Funding: Swiss Federal Office of Public Health, Fondation CHUV.

[Spatulas: A Franco-Colombian story or the slow rise of propulsion...] / Les spatules : une histoire franco-colombienne ou la lente ascension de la propulsion .

The idea of using an instrument to assist natural childbirth is not new and it was in the 18th and 19th centuries that the forceps was developed. It is only after the Second World War that the suction cup provides an alternative to instrumental childbirth, but still based on prehension and traction. In 1950, Emile Thierry, in France, presented his spatulas based on the then original principle of propulsion. The diffusion of spatulas is almost non-existent in the Anglo-Saxon world but is not limited to France since its use was real by the Iberians and Latin Americans. There are currently three types of spatula, two of which are French and one Colombian. This review takes up the saga of this instrument for more than 70 years, develops its particularities and describes the present literature.

Radioisotope-guided Lymphadenectomy for Pelvic Lymph Node Staging in Patients With Intermediate- and High-risk Prostate Cancer (The Prospective SENTINELLE Study).

PURPOSE: Our aim was to prospectively evaluate the diagnostic accuracy of sentinel lymph node biopsy-guided lymph node dissection compared to extended pelvic lymph node dissection in patients with intermediate- or high-risk prostate cancer. MATERIALS AND METHODS: We conducted a prospective, single-arm, multicenter study at 3 tertiary centers in France between February 2012 and May 2019. Eligible patients had clinically localized intermediate- or high-risk prostate cancer. After intraprostatic injection of (99m)Tc-nanocolloid, the locations of the sentinel lymph nodes were defined by preoperative lymphoscintigraphy. Surgical excision of the sentinel lymph nodes was performed using intraoperative gamma probe guidance. After resection of the sentinel lymph nodes, extended pelvic lymph node dissection was performed in all patients. We assessed the diagnostic accuracy of the sentinel lymph node biopsy method using extended pelvic lymph node dissection as the reference standard. This trial was registered in ClinicalTrials.gov (NCT02732392). RESULTS: A total of 162 men cN0M0 (CT scan and bone scan) were enrolled: 106 (65.4%) and 56 (34.6%) patients had intermediate- and high-risk prostate cancer, respectively. The median number of nodes retrieved was 14 (mean 16, IQR 10-21) per patient. At final pathological analysis, 22 patients (13.6%) were pN+. Sensitivity, specificity, negative predictive value, and positive predictive value of sentinel lymph node biopsy method in detecting patients with at least 1 lymph node metastasis were 95.4% (95% CI, 75.1-99.7), 100% (95% CI, 96.6-100), 99.2% (95% CI, 95.5-99.9), and 100% (95% CI, 80.7-100), respectively. CONCLUSIONS: Our multicenter prospective study supports that sentinel lymph node biopsy is a very effective and sensitive method for pelvic lymph node staging in patients with intermediate- or high-risk localized prostate cancer.

Head-to-perineum distance measured transperineally as a predictor of failed midcavity vacuum-assisted delivery.

BACKGROUND: During the second stage of labor, in case of a need for a fetal extraction at midcavity, the choice of attempting the procedure between operative vaginal delivery and cesarean delivery is difficult. Moreover, guidelines on this subject are not clear. OBJECTIVE: This study aimed to identify antenatal and intrapartum parameters associated with a failed midcavity vacuum-assisted delivery and its association with maternal and neonatal adverse outcomes. STUDY DESIGN: This was a single-center, retrospective, cohort study conducted at a tertiary maternity hospital in France from January 2010 to December 2020. Women with singleton pregnancies under epidural analgesia with nonanomalous cephalic presenting fetuses and gestational ages at ≥37 weeks of gestation, who were submitted to midcavity vacuum-assisted delivery, were included. Following the American College of Obstetricians and Gynecologists definition, midcavity was defined as the presenting part of the fetus (ie, the fetal head) found at stations 0 and +1. For research purposes, all patients were submitted to transperineal ultrasound to evaluate the head-to-perineum distance, however, this measurement did not affect the decision to perform a midcavity vacuum-assisted delivery. The primary outcome of the study was failed midcavity vacuum-assisted delivery leading to cesarean delivery or the use of a different instrument to achieve vaginal delivery. RESULTS: Overall, 951 cases of midcavity vacuum-assisted delivery were included in this study. Failed midcavity vacuum-assisted delivery occurred in 242 patients (25.4%). Factors independently associated with failed midcavity vacuum-assisted delivery included maternal height (adjusted odds ratio, 0.96; 95% confidence interval, 0.94-0.99; P=.002), duration of the active phase of the first stage of labor (adjusted odds ratio, 1.11; 95% confidence interval, 1.05-1.17; P<.001), nonocciput anterior fetal head position (adjusted odds ratio, 1.47; 95% confidence interval, 1.06-2.04; P=.02), z score of the head-to-perineum distance (adjusted odds ratio, 1.23; 95% confidence interval, 1.05-1.43; P=.01), and birthweight of >4000 g (adjusted odds ratio, 2.04; 95% confidence interval, 1.28-3.26; P=.003). Women submitted to a failed midcavity vacuum-assisted delivery were more likely to have a major postpartum hemorrhage (7.1% vs 2.0%; P<.001), whereas neonates were more likely to have an umbilical artery pH of <7.1 (30.5% vs 19.8%; P=.001), be admitted to the neonatal intensive care unit (9.6% vs 4.7%; P=.005), and have a severe caput succedaneum (14.9% vs 0.7%; P<.001). Subgroup analysis on all patients with a fetal head station of 0 found that the head-to-perineum distance was the only independent variable associated with failed midcavity vacuum-assisted delivery (adjusted odds ratio, 1.66; 95% confidence interval, 1.29-2.12; P<.001). The area under the receiving operating characteristic curve of the head-to-perineum distance in this subgroup population was 0.67 (95% confidence interval, 0.60-0.73; P<.001), and the optimal cutoff point of the head-to-perineum distance measurement discriminating between failed and successful midcavity vacuum-assisted deliveries was 55 mm. It was associated with a 0.90 (95% confidence interval, 0.83-0.95) sensitivity, 0.19 (95% confidence interval, 0.14-0.25) specificity, 0.36 (95% confidence interval, 0.30-0.42) positive predictive value, and 0.80 (95% confidence interval, 0.66-0.90) negative predictive value. CONCLUSION: Study data showed that a high fetal head station, measured using the head-to-perineum distance, and a nonocciput anterior position of the fetal head are independently associated with failed midcavity vacuum-assisted delivery. The result supported the systematic assessment of the sonographic head station and position before performing a midcavity vacuum-assisted delivery.