Natural History and Clinicopathological Associations of TRPC6-Associated Podocytopathy.

BACKGROUND: Understanding the genetic basis of human diseases has become integral to drug development and precision medicine. Recent advancements have enabled the identification of molecular pathways driving diseases, leading to targeted treatment strategies. The increasing investment in rare diseases by the biotech industry underscores the importance of genetic evidence in drug discovery and approval processes. Here we studied a monogenic Mendelian kidney disease, TRPC6-associated podocytopathy (TRPC6-AP), to present its natural history, genetic spectrum, and clinicopathological associations in a large cohort of patients with causal variants in TRPC6, in order to help define the specific features of disease and further facilitate drug development and clinical trials design. METHODS: the study involved 64 individuals from 39 families with TRPC6 causal missense variants. Clinical data, including age of onset, laboratory results, response to treatment, kidney biopsy findings, and genetic information, were collected from multiple centers nationally and internationally. Exome or targeted sequencing was performed and variant classification was based on strict criteria. Structural and functional analyses of TRPC6 variants were conducted to understand their impact on protein function. In depth re-analysis of light and electron microscopy specimens for 9 available kidney biopsies was conducted to identify pathological features and correlates of TRPC6-AP. RESULTS: Large-scale sequencing data did not support causality for TRPC6 protein-truncating variants. We identified 21 unique TRPC6 missense variants, clustering in three distinct regions of the protein, and with different effects on TRPC6 3D protein structure. Kidney biopsy analysis revealed FSGS patterns of injury in most cases, along with distinctive podocyte features including diffuse foot process effacement and swollen cell bodies. The majority of patients presented in adolescence or early adulthood but with ample variation (average 22, SD ± 14 years), with frequent progression to kidney failure but with variability in time between presentation and ESKD. CONCLUSIONS: This study provides insights into the genetic spectrum, clinicopathological associations, and natural history of TRPC6-AP.

Initial empirical antibiotic therapy in kidney transplant recipients with pyelonephritis: A global survey of current practice and opinions across 19 countries on six continents.

BACKGROUND: Despite the burden of pyelonephritis after kidney transplantation, there is no consensus on initial empirical antibiotic management. METHODS: We surveyed clinicians throughout the world on their practice and opinions about the initial empirical therapy of post-transplant pyelonephritis, using clinical vignettes. A panel of experts from 19 countries on six continents designed this survey, and invited 2145 clinicians to participate. RESULTS: A total of 721 clinicians completed the survey (response rate: 34%). In the hypothetical case of a kidney transplant recipient admitted with pyelonephritis but not requiring intensive care, most respondents reported initiating either a 3rd-generation cephalosporin (37%) or piperacillin-tazobactam (21%) monotherapy. Several patient-level factors dictated the selection of broader-spectrum antibiotics, including having a recent urine culture showing growth of a resistant organism (85% for extended-spectrum ß-lactamase-producing organisms, 90% for carbapenemase-producing organisms, and 94% for Pseudomonas aeruginosa). Respondents attributed high importance to the appropriateness of empirical therapy, which 87% judged important to prevent mortality. Significant practice and opinion variations were observed between and within countries. CONCLUSION: High-quality studies are needed to guide the empirical management of post-transplant pyelonephritis. In particular, whether prior urine culture results should systematically be reviewed and considered remains to be determined. Studies are also needed to clarify the relationship between the appropriateness of initial empirical therapy and outcomes of post-transplant pyelonephritis.

Endometriosis-associated ovarian cancer: a different clinical entity.

OBJECTIVE: To compare survival outcomes and patterns of recurrence between endometriosis-associated ovarian cancer patients and non-endometriosis-associated ovarian cancer patients. METHODS: This retrospective study included data of consecutive patients with endometrioid or clear cell ovarian cancer treated at the Fondazione IRCCS Istituto Nazionale dei Tumori di Milano between January 2010 and June 2021. Patients were assigned to one of two groups according to the absence or presence of endometriosis together with ovarian cancer at final histological examination. Survival outcomes were assessed using Kaplan-Meier and Cox hazard models. Proportions in recurrence rate and pattern of recurrence were evaluated using the Fisher exact test. RESULTS: Overall, 83 women were included in the endometriosis-associated ovarian cancer group and 144 in the non-endometriosis-associated ovarian cancer group, respectively. Patients included in the non- endometriosis-associated ovarian cancer group had a shorter disease-free survival than those in the endometriosis-associated ovarian cancer group (23.4 (range 2.0-168.9) vs 60.9 (range 4.0-287.8) months; p<0.001). Univariable and multivariable analyses showed that the association with endometriosis, previous hormonal treatment, early stage at presentation, and endometrioid histology were related to better disease-free survival in the entire study population. Similarly, patients in the non-endometriosis-associated ovarian cancer group had a shorter median (range) overall survival than those in the endometriosis-associated ovarian cancer group (54.4 (range 0.7-190.6) vs 77.6 (range 4.5-317.8) months; p<0.001). Univariable and multivariable analyses showed that younger age at diagnosis, association with endometriosis, and early stage at presentation were related to better overall survival. The recurrence rate was higher in the non-endometriosis-associated ovarian cancer group (63/144 women, 43.8%) than in the endometriosis-associated ovarian cancer group (17/83 women, 20.5%; p<0.001). CONCLUSIONS: Endometriosis-associated ovarian cancer patients had significantly longer disease-free survival and overall survival than non-endometriosis-associated ovarian cancer patients, while the recurrence rate was higher in non-endometriosis-associated ovarian cancer patients.

Fertility-sparing treatment with conization versus radical hysterectomy in patients with early-stage cervical cancer: inverse propensity score weighted analysis.

OBJECTIVE: To report 20 years of experience with fertility-sparing surgery for patients with early-stage cervical cancer, comparing the oncological outcomes with outcomes for those who underwent a radical hysterectomy. METHODS: Patients with pre-operative stage IA1 with lymphovascular space invasion, IA2 and IB1 cervical cancer (any grade) were included (2018 International Federation of Gynecology and Obstetrics staging system). Inclusion criteria comprised age (18-44 years), histology (squamous, adenocarcinoma, or adenosquamous) and absence of previous/concomitant cancer. A thorough counseling about oncological and obstetrical potential risks was mandatory for patients asking for fertility sparing. Results for consecutive patients who underwent fertility-sparing surgery (cervical conization and nodal evaluation) were analyzed and compared with results for patients treated with radical surgery. Oncological outcomes were assessed with a propensity score adjustment with inverse probability of treatment weighting. RESULTS: Overall, 109 patients were included in the study. Ten patients abandoned the fertility-sparing route because of nodal involvement (n=5), margin positive (n=2), or because patients requested radical treatment (n=3). Sentinel node mapping was performed in 19 of 49 (38.8%) patients in the fertility-sparing surgery group. Among the patients in the fertility-sparing group, 6 (12.2%) patients relapsed. 34 (69.4%) patients attempted to conceive. Pre-operative covariates selected to define the probability of having either fertility-sparing or radical surgery were well balanced using inverse probability of treatment weighting. Pathological features were similar between the groups, including grading, histotype, stage, and lymphovascular space invasion. After a median follow-up of 38.8 (range 5-186) months there were no differences in progression-free survival (p=0.32) and overall survival (p=0.74) between the fertility-sparing and radical hysterectomy groups. The results after inverse probability of treatment weighting adjustment did not show significant differences in progression-free survival (p=0.72) and overall survival (p=0.71) between the groups. CONCLUSION: Fertility-sparing surgery based on conization plus laparoscopic lymph node evaluation, may be considered safe and effective for patients with early-stage cervical cancer.

Pelvic Neuro-Visualization: An Anatomical Illustration of the Autonomic Pelvic Nervous Network in Gynecologic Surgery.

OBJECTIVE: During radical pelvic surgeries fibers of the autonomic pelvic nervous network can be accidentally damaged leading to significant visceral sequelae, which dramatically affect women's quality of life because of urinary, anorectal, and sexual postoperative dysfunctions.1,2 Direct visualization is one way to preserve hypogastric nerves (HNs), pelvic splanchnic nerves (PSNs), and the bladder branches from the inferior hypogastric plexus (IHP). However, the literature lacks critical photos and/or illustrations that are necessary to understand the precise anatomy needed to preserve the pelvic autonomic fibers. DESIGN: Narrated laparoscopic video footage for identifying, dissecting, and preserving the autonomic nerve bundles during pelvic surgery. SETTING: Tertiary level hospital-"IRCCS Istituto Nazionale dei Tumori", Milano, Italy. INTERVENTIONS: Visceral pelvic innervation is established by the superior hypogastric plexus(SHP) located anteriorly to the aortic bifurcation and the median sacral vessels and carries mostly sympathetic fibers. SHP divides in front of the sacrum into the right and left HN. At the level of the paracervix, the HNs join the parasympathetic PSNs coming out from sacral root S2, S3, S4 to form the IHP.2-5 Here, we performed laparoscopic surgery, before "Laparoscopic Approach to Cervical Cancer" trial (LACC) era, identifying key anatomic landmarks useful to highlight the path of the most commonly encountered autonomic pelvic nerves in gynecologic radical surgery: during the narration we describe and illustrate the procedure to identify all autonomic pelvic nerves, the sympathetic fibers, the PSNs, and the bladder branch emerging from the IHP in order to preserve their anatomic and functional integrity. This technique is anatomically and surgically indicated for adequate removal of the parametrical issues and vagina while preserving the total pelvic nervous system. CONCLUSION: Nerve-sparing surgery reduces bowel-, bladder- and sexual- dysfunction without decreasing surgical efficacy.1,2 To accomplish safe and effective surgery, comprehension of the 3 dimensional structure of the vascular and nerve anatomy in the pelvis is essential. This video provides a great resource to educate surgeons, especially the youngest ones, about the retroperitoneal nervous networking: we identified the autonomic nerve pathway from adjacent tissues along the pathway consisting of cardinal, sacro-uterine, rectouterine/vaginal, and vesico-uterine ligaments.

Management of Uterine Fibroids and Sarcomas: The Palermo Position Paper.

BACKGROUND: Uterine fibroids are benign monoclonal tumors originating from the smooth muscle cells of the myometrium, constituting the most prevalent pathology within the female genital tract. Uterine sarcomas, although rare, still represent a diagnostic challenge and should be managed in centers with adequate expertise in gynecological oncology. OBJECTIVES: This article is aimed to summarize and discuss cutting-edge elements about the diagnosis and management of uterine fibroids and sarcomas. METHODS: This paper is a report of the lectures presented in an expert meeting about uterine fibroids and sarcomas held in Palermo in February 2023. OUTCOME: Overall, the combination of novel molecular pathways may help combine biomarkers and expert ultrasound for the differential diagnosis of uterine fibroids and sarcomas. On the one hand, molecular and cellular maps of uterine fibroids and matched myometrium may enhance our understanding of tumor development compared to histologic analysis and whole tissue transcriptomics, and support the development of minimally invasive treatment strategies; on the other hand, ultrasound imaging allows in most of the cases a proper mapping the fibroids and to differentiate between benign and malignant lesions, which need appropriate management. CONCLUSIONS AND OUTLOOK: The choice of uterine fibroid management, including pharmacological approaches, surgical treatment, or other strategies, such as high-intensity focused ultrasound (HIFU), should be carefully considered, taking into account the characteristics of the patient and reproductive prognosis.

Inequities in Organ Donation and Transplantation Among Immigrant Populations in Italy: A Narrative Review of Evidence, Gaps in Research and Potential Areas for Intervention.

Immigrants from outside Europe have increased over the past two decades, especially in Southern European countries including Italy. This influx coincided with an increased number of immigrants with end-stage organ diseases. In this narrative review, we reviewed evidence of the gaps between native-born and immigrant populations in the Organ Donation and Transplantation (ODT) process in Italy. Consistent with prior studies, despite the availability of a publicly funded health system with universal healthcare coverage, non-European-born individuals living in Italy are less likely to receive living donor kidney transplantation and more likely to have inferior long-term kidney graft function compared with EU-born and Eastern European-born individuals. While these patients are increasingly represented among transplant recipients (especially kidney and liver transplants), refusal rates for organ donation are higher in some ethnic groups compared with native-born and other foreign-born referents, with the potential downstream effects of prolonged waiting times and inferior transplant outcomes. In the process, we identified gaps in relevant research and biases in existing studies. Given the Italian National Transplant Center's (CNT) commitment to fighting inequities in ODT, we illustrated actions taken by CNT to tackle inequities in ODT among immigrant communities in Italy.

Real-time Fluorescent ICG and 99m-Tc Nanocolloid Tracer Navigation in Bilateral Sentinel Lymph Node Mapping of Vulvar Cancer.

STUDY OBJECTIVE: The effectiveness of sentinel lymph node (SLN) biopsy has been validated by 2 prospective trials, GROINS VI and GOG 173 [1,2]. According to the European Society of Gynaecological Oncology guideline in patients with unifocal tumors with a diameter of <4 cm, in the absence of suspected inguinal lymph nodes, SLN biopsy is recommended. The use of a radioactive tracer is mandatory [2]. Using indocyanine green (ICG) increases the detection of the vulvar sentinel node from 89.7% to 100% [3]. This video aimed to share our experience about the feasibility, safety, and usefulness of the surgical identification of SLN in vulvar cancer using real-time fluorescent ICG with 99m-technetium (Tc) nanocolloid. DESIGN: A stepwise demonstration of the technique with narrated video footage. SETTING: Tertiary level hospital "IRCCS Istituto Nazionale dei Tumori," Milano, Italy. INTERVENTIONS: A 50-year-old woman was diagnosed as having vulvar cancer on biopsy of 1.5 cm size vulvar lesion under the clitoris area and referred to our operative unit. F-18 fluorodeoxyglucose positron emission tomography computed tomography showed no extravulvar disease. The patient was scheduled for radical vulvectomy and bilateral inguinal SLN biopsy. (Video still 1) In this video, the surgical procedure involved double location of SLN, first with the 99m-Tc detector followed by ICG identification. We used an ICG dilution of 2.5 mg/mL in sterile water and injected 4 mL around the tumor 5 to 10 minutes before visualization. First a handheld gamma probe used to identify the location of the SLNs with 99m-Tc. The fluorescence imaging was performed by the quest imaging system (FLUOPTICS, Middenmeer, The Netherlands) that combines autofluorescence and fluorescence perfusion imaging (Video Still 2). Second, we performed the SLN biopsy using a dark mode procedure to identify the IGC tracer (Video Still 3). The fluorescence imaging enables the detection of these markers through some millimeters of tissue, and ICG has the advantage that is visible through the skin [4]. CONCLUSION: This video shows a successful combined 99m-Tc and ICG fluorescence image-guided bilateral SLN biopsy in a vulvar cancer patient using a near-infrared optical imaging system (FLUOPTICS). ICG for SLN mapping seems to be safe in women with vulvar cancer with a satisfactory detection rate. This may help in retaining surgical radicality while minimizing operative complications.

Assessment of pre-donation glomerular filtration rate: going back to basics.

The 2017 version of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines is the most recent international framework for the evaluation and care of living kidneys donors. Along with the call for an integrative approach evaluating the long-term end-stage kidney disease risk for the future potential donor, several recommendations are formulated regarding the pre-donation glomerular filtration rate (GFR) adequacy with no or little consideration for the donor candidate's age or for the importance of using reference methods of GFR measurements. Herein, we question the position of the KDIGO guidelines and discuss the rationale and modalities for a more basic, but no less demanding GFR evaluation enabling a more efficient selection of potential kidney donors.

Hypophosphatemia in critically ill patients undergoing Sustained Low-Efficiency Dialysis with standard dialysis solutions.

BACKGROUND: In patients admitted to the Intensive Care Unit (ICU), Kidney Replacement Therapy (KRT) is an important risk factor for hypophosphataemia. However, studies addressing the development of hypophosphatemia during prolonged intermittent KRT modalities are lacking. Thus, we evaluated the incidence of hypophosphatemia during Sustained Low-Efficiency Dialysis (SLED) in ICU patients; we also examined the determinants of post-SLED serum phosphate level (s-P) and the relation between s-P and phosphate supplementation and ICU mortality. METHODS: We conducted a retrospective analysis on a cohort of critically ill patients with severe renal failure and KRT need, who underwent at least three consecutive SLED sessions at 24-72 h time intervals with daily monitoring of s-P concentration. SLED with Regional Citrate Anticoagulation (RCA) was performed with either conventional dialysis machines or continuous-KRT monitors and standard dialysis solutions. When deemed necessary by the attending physician, intravenous phosphate supplementation was provided by sodium glycerophosphate pentahydrate. We used mixed-effect models to examine the determinants of s-P and Cox proportional hazards regression models with time-varying covariates to examine the adjusted relation between s-P, intravenous phosphate supplementation and ICU mortality. RESULTS: We included 65 patients [mean age 68 years (SD 10.0); mean Acute Physiology and Chronic Health Evaluation II score 25 (range 9-40)] who underwent 195 SLED sessions. The mean s-P before the start of the first SLED session (baseline s-P) was 5.6 ± 2.1 mg/dL (range 1.5-12.3). Serum phosphate levels at the end of each SLED decreased with increasing age, SLED duration and number of SLED sessions (P < .05 for all). The frequency of hypophosphatemia increased after the first through the third SLED session (P = .012). Intravenous phosphate supplementation was scheduled after 12/45 (26.7%) SLED sessions complicated by hypophosphataemia. The overall ICU mortality was 23.1% (15/65). In Cox regression models, after adjusting for potential confounders and for current s-P, intravenous phosphate supplementation was associated with a decrease in ICU mortality [adjusted hazard ratio: 0.24 (95% confidence interval: 0.06 to 0.89; P = 0.033)]. CONCLUSIONS: Hypophosphatemia is a frequent complication in critically ill patients undergoing SLED with standard dialysis solutions, that worsens with increasing SLED treatment intensity. In patients undergoing daily SLED, phosphate supplementation is strongly associated with reduced ICU mortality.

Issues regarding COVID-19 in kidney transplantation in the ERA of the Omicron variant: a commentary by the ERA Descartes Working Group.

The Omicron variant, which has become the dominant strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) worldwide, brings new challenges to preventing and controlling the infection. Moreover, the widespread implementation of vaccination policies before and after transplantation, and the development of new prophylactic and treatment strategies for coronavirus disease 2019 (COVID-19) over the past 12-18 months, has raised several new issues concerning kidney transplant recipients. In this special report, the ERA DESCARTES (Developing Education Science and Care for Renal Transplantation in European States) Working Group addresses several questions related to everyday clinical practice concerning kidney transplant recipients and to the assessment of deceased and live kidney donors: what is the current risk of severe disease and of breakthrough infection, the optimal management of immunosuppression in kidney transplant recipients with COVID-19, the role of passive immunization and the efficacy of antiviral drugs in ambulatory patients, the management of drug-to-drug interactions, safety criteria for the use of SARS-CoV-2-positive donors, issues related to the use of T cell depleting agents as induction treatment, and current recommendations for shielding practices.

Kidney transplantation during mass disasters - from COVID-19 to other catastrophes A Consensus Statement by the DESCARTES Working Group and Ethics Committee of the ERA.

Mass disasters are characterized by a disparity between health care demand and supply, which hampers complex therapies like kidney transplantation. Considering scarcity of publications on previous disasters, we reviewed transplantation practice during the recent COVID-19 pandemic, and dwelled upon this experience for guiding transplantation strategies in the future pandemic and non-pandemic catastrophes. We strongly suggest continuing transplantation programs during mass disasters, if medical and logistic operational circumstances are appropriate. Postponing transplantations from living donors and referral of urgent cases to safe regions or hospitals are justified. Specific preventative measures in anticipated disasters (such as vaccination programs during pandemics or evacuation in case of hurricanes or wars) may be useful to minimize risks. Immunosuppressive therapies should consider stratifying risk status and avoiding heavy immune suppression in patients with a low probability of therapeutic success. Discharging patients at the earliest convenience is justified during pandemics, whereas delaying discharge is reasonable in other disasters, if infrastructural damage results in unhygienic living environments for the patients. In the outpatient setting, telemedicine is a useful approach to reduce the patient load to hospitals, to minimize the risk of nosocomial transmission in pandemics and the need for transport in destructive disasters. If it comes down to save as many lives as possible, some ethical principles may vary in function of disaster circumstances, but elementary ethical rules are non-negotiable. Patient education is essential to minimize disaster-related complications and to allow for an efficient use of health care resources.

Kidney transplantation during mass disasters - from COVID-19 to other catastrophes.

Mass disasters are characterized by a disparity between health care demand and supply, which hampers complex therapies like kidney transplantation. Considering scarcity of publications on previous disasters, we reviewed transplantation practice during the recent COVID-19 pandemic, and dwelled upon this experience for guiding transplantation strategies in the future pandemic and non-pandemic catastrophes. We strongly suggest continuing transplantation programs during mass disasters, if medical and logistic operational circumstances are appropriate. Postponing transplantations from living donors and referral of urgent cases to safe regions or hospitals are justified. Specific preventative measures in anticipated disasters (such as vaccination programs during pandemics or evacuation in case of hurricanes or wars) may be useful to minimize risks. Immunosuppressive therapies should consider stratifying risk status and avoiding heavy immune suppression in patients with a low probability of therapeutic success. Discharging patients at the earliest convenience is justified during pandemics, whereas delaying discharge is reasonable in other disasters, if infrastructural damage results in unhygienic living environments for the patients. In the outpatient setting, telemedicine is a useful approach to reduce the patient load to hospitals, to minimize the risk of nosocomial transmission in pandemics and the need for transport in destructive disasters. If it comes down to save as many lives as possible, some ethical principles may vary in function of disaster circumstances, but elementary ethical rules are non-negotiable. Patient education is essential to minimize disaster-related complications and to allow for an efficient use of health care resources.

Prolonged-Release Once-Daily Formulation of Tacrolimus Versus Standard-of-Care Tacrolimus in de novo Kidney Transplant Patients Across Europe.

Background: Tacrolimus is the calcineurin inhibitor of choice for preventing acute rejection episodes in kidney transplant patients. However, tacrolimus has a narrow therapeutic range that requires regular monitoring of blood concentrations to minimize toxicity. A new once-daily tacrolimus formulation, LCP-tacrolimus (LCPT), has been developed, which uses MeltDose™ drug-delivery technology to control drug release and enhance overall bioavailability. Our study compared dosing of LCPT with current standard-of-care tacrolimus [immediate-release tacrolimus (IR-Tac) or prolonged-release tacrolimus (PR-Tac)] during the 6 months following de novo kidney transplantation. Comparisons of graft function, clinical outcomes, safety, and tolerability for LCPT versus IR-Tac/PR-Tac were also performed. Methods: Standard immunological risk patients with end-stage renal disease who had received a de novo kidney transplant were randomized (1:1) to LCPT (N = 200) or IR-Tac/PR-Tac (N = 201). Results: Least squares (LS) mean tacrolimus total daily dose from Week 3 to Month 6 was significantly lower for LCPT than for IR-Tac/PR-Tac. Although LS mean tacrolimus trough levels were significantly higher for LCPT than IR-Tac/PR-Tac, tacrolimus trough levels remained within the standard reference range for most patients. There were no differences between the groups in treatment failure measures or safety profile. Conclusion: LCPT can achieve similar clinical outcomes to other tacrolimus formulations, with a lower daily dose. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT02432833.

Kidney transplantation and withdrawal rates among wait-listed first-generation immigrants in Italy.

BACKGROUND: Multiple barriers diminish access to kidney transplantation (KT) in immigrant compared to non-immigrant populations. It is unknown whether immigration status reduces the likelihood of KT after wait-listing despite universal healthcare coverage with uniform access to transplantation. METHODS: We retrospectively collected data of all adult waiting list (WL) registrants in Italy (2010-20) followed for 5 years until death, KT in a foreign center, deceased-donor kidney transplant (DDKT), living-donor kidney transplant (LDKT) or permanent withdrawal from the WL. We calculated adjusted relative probability of DDKT, LDKT and permanent WL withdrawal in different immigrant categories using competing-risks multiple regression models. RESULTS: Patients were European Union (EU)-born (n = 21 624), Eastern European-born (n = 606) and non-European-born (n = 1944). After controlling for age, sex, blood type, dialysis vintage, case-mix and sensitization status, non-European-born patients had lower LDKT rates compared to other immigrant categories: LDKT adjusted relative probability of non-European-born vs. Eastern European-born 0.51 (95% CI: 0.33-0.79; P = 0.002); of non-European-born vs. EU-Born: 0.65 (95% CI: 0.47-0.82; P = 0.001). Immigration status did not affect the rate of DDKT or permanent WL withdrawal. CONCLUSIONS: Among EU WL registrants, non-European immigration background is associated with reduced likelihood of LDKT but similar likelihood of DDKT and permanent WL withdrawal. Wherever not available, new national policies should enable coverage of travel and medical fees for living-donor surgery and follow-up for non-resident donors to improve uptake of LDKT in immigrant patients, and provide KT education that is culturally competent, individually tailored and easily understandable for patients and their potential living donors.

Native Tissue Posterior Compartment Repair for Isolated Posterior Vaginal Prolapse: Anatomical and Functional Outcomes.

Background and Objectives: Posterior compartment prolapse is associated with constipation and obstructed defecation syndrome. However, there is still a lack of consensus on the optimal treatment for this condition. We aim to investigate functional, anatomical, and quality-of-life outcomes of native tissue transvaginal repair of isolated symptomatic rectocele. Materials and Methods: We retrospective analyzed patients who underwent transvaginal native tissue repair for stage ≥ II and symptomatic posterior vaginal wall prolapse between January 2018 and June 2021. Anatomical and functional outcomes were evaluated. Wexner constipation score was used to assess bowel symptoms, while the Patient Global Impression of Improvement (PGI-I) score was used to evaluate subjective satisfaction after surgery. Results: Twenty-eight patients were included in the analysis. The median age was 64.5 years, and half of them underwent a previous hysterectomy for benign reasons. The median follow-up time was 33.5 months. A significant anatomical improvement in the posterior compartment was noticed compared with preoperative assessment (p < 0.001 for Ap and Bp), with only two (7.1%) anatomical recurrences. Additionally, obstructed defecation symptoms decreased significantly compared to baseline (p < 0.001), as well as vaginal bulging, with no new-onset cases of fecal incontinence or de novo dyspareunia. PGI-I resulted in 89.2% of patients being satisfied (PGI-I ≥ 2), with a median score of 1.5. Conclusions: Transvaginal native tissue repair for isolated posterior prolapse is safe and effective in managing bowel symptoms, with excellent anatomical and functional outcomes and satisfactory improvement in patients' quality of life.

Sentinel node mapping vs. sentinel node mapping plus back-up lymphadenectomy in high-risk endometrial cancer patients: Results from a multi-institutional study.

OBJECTIVE: Sentinel node mapping (SLN) has replaced lymphadenectomy for staging surgery in apparent early-stage low and intermediate risk endometrial cancer (EC). Only limited data about the adoption of SNM in high risk EC is still available. Here, we evaluate the outcomes of high-risk EC undergoing SNM (with or without back-up lymphadenectomy). METHODS: This is a multi-institutional international retrospective study, evaluating data of high-risk (FIGO grade 3 endometrioid EC with myometrial invasion >50% and non-endometrioid histology) EC patients undergoing SNM followed by back-up lymphadenectomy and SNM alone. RESULTS: Chart of consecutive 196 patients were evaluated. The study population included 83 and 113 patients with endometrioid and non-endometrioid EC, respectively. SNM alone and SNM followed by back-up lymphadenectomy were performed in 50 and 146 patients, respectively. Among patients having SNM alone, 14 (28%) were diagnosed with nodal disease. In the group of patients undergoing SNM plus back-up lymphadenectomy 34 (23.2%) were diagnosed with nodal disease via SNM. Back-up lymphadenectomy identified 2 (1%) additional patients with nodal disease (in the para-aortic area). Back-up lymphadenectomy allowed to remove adjunctive positive nodes in 16 (11%) patients. After the adoption of propensity-matched algorithm, we observed that patients undergoing SNM plus back-up lymphadenectomy experienced similar disease-free survival (p = 0.416, log-rank test) and overall survival (p = 0.940, log-rank test) than patients undergoing SLN alone. CONCLUSIONS: Although the small sample size, and the retrospective study design this study highlighted that type of nodal assessment did not impact survival outcomes in high-risk EC. Theoretically, back-up lymphadenectomy would be useful in improving the removal of positive nodes, but its therapeutic value remains controversial. Further prospective evidence is needed.

Fertility in patients with untreated rectosigmoid endometriosis.

RESEARCH QUESTION: Several studies have investigated reproductive outcomes following surgical treatment of colorectal endometriosis, mainly segmental colorectal resection. This study examines pregnancy and live birth rates of women with rectosigmoid endometriosis not treated by surgery. DESIGN: A retrospective analysis of data collected between May 2009 and January 2020 related to 215 women affected by rectosigmoid endometriosis wishing to conceive. Patients had a diagnosis of rectosigmoid endometriosis by transvaginal ultrasonography and magnetic resonance imaging enema. Patients with estimated bowel stenosis >70% at computed tomographic colonography and/or subocclusive/occlusive symptoms were excluded. RESULTS: During the median length of follow-up of 31 months (range 13-63 months), the total pregnancy and live birth rates of the study population were 47.9% and 45.1%, respectively. Sixty-two women had a live birth after natural conception (28.8%; 95% confidence interval [CI] 22.8-35.6%) with a median time required to conceive of 10 months (range 2-34 months). Eighty-three women underwent infertility treatments (38.6%, 95% CI 32.1-45.5%); among these, 68 patients underwent IVF either directly (n = 51) or after intrauterine insemination (IUI) failure (n = 17). Time to conception was significantly higher in women having conceived by IVF than in those having conceived naturally (P < 0.001) or by IUI (P = 0.006). In patients undergoing IVF cycles, a worsening of some pain and intestinal symptoms was observed. CONCLUSIONS: At median follow-up of 31 months, women with rectosigmoid endometriosis have a 48% pregnancy rate. However, these patients must be referred to centres specialized in managing endometriosis to properly assess symptoms and degree of bowel stenosis.

Management of obesity in kidney transplant candidates and recipients: A clinical practice guideline by the DESCARTES Working Group of ERA.

The clinical practice guideline Management of Obesity in Kidney Transplant Candidates and Recipients was developed to guide decision-making in caring for people with end-stage kidney disease (ESKD) living with obesity. The document considers the challenges in defining obesity, weighs interventions for treating obesity in kidney transplant candidates as well as recipients and reflects on the impact of obesity on the likelihood of wait-listing as well as its effect on transplant outcomes. It was designed to inform management decisions related to this topic and provide the backdrop for shared decision-making. This guideline was developed by the European Renal Association's Developing Education Science and Care for Renal Transplantation in European States working group. The group was supplemented with selected methodologists to supervise the project and provide methodological expertise in guideline development throughout the process. The guideline targets any healthcare professional treating or caring for people with ESKD being considered for kidney transplantation or having received a donor kidney. This includes nephrologists, transplant physicians, transplant surgeons, general practitioners, dialysis and transplant nurses. Development of this guideline followed an explicit process of evidence review. Treatment approaches and guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence and the strength of recommendations followed the Grading of Recommendations Assessment, Development and Evaluation approach. Limitations of the evidence are discussed and areas of future research are presented.

Long-term risks after kidney donation: how do we inform potential donors? A survey from DESCARTES and EKITA transplantation working groups.

BACKGROUND: Publications from the last decade have increased knowledge regarding long-term risks after kidney donation. We wanted to perform a survey to assess how transplant professionals in Europe inform potential kidney donors regarding long-term risks. The objectives of the survey were to determine how they inform donors and to what extent, and to evaluate the degree of variation. METHODS: All transplant professionals involved in the evaluation process were considered eligible, regardless of the type of profession. The survey was dispatched as a link to a web-based survey. The subjects included questions on demographics, the information policy of the respondent and the use of risk calculators, including the difference of relative and absolute risks and how the respondents themselves understood these risks. RESULTS: The main finding was a large variation in how often different long-term risks were discussed with the potential donors, i.e. from always to never. Eighty percent of respondents stated that they always discuss the risk of end-stage renal disease, while 56% of respondents stated that they always discuss the risk of preeclampsia. Twenty percent of respondents answered correctly regarding the relationship between absolute and relative risks for rare outcomes. CONCLUSIONS: The use of written information and checklists should be encouraged. This may improve standardization regarding the information provided to potential living kidney donors in Europe. There is a need for information and education among European transplant professionals regarding long-term risks after kidney donation and how to interpret and present these risks.