Centralizing surgery for ovarian cancer in a 'non-centralizing' country (Belgium): the UNGO (UCLouvain Network of Gynaecological Oncology) experience.

OBJECTIVE: In Belgium there is no centralization of surgery for ovarian cancer, with more than 100 centers treating around 800 cases per year. In 2017 a network with several collaborating hospitals was established to centralize surgery for ovarian cancer (UCLouvain Network of Gynecological Oncology; UNGO) following publication of the European Society of Gynecological Oncology (ESGO) recommendations and quality criteria for surgery of advanced ovarian cancer. We obtained ESGO accreditation in 2019. METHODS: We retrospectively collected data associated with patients undergoing surgery in our institution from 2007 to 2016, before the creation of the network (cohort 1) and, following the establishment of UNGO (2017-2021), patients undergoing surgery were prospectively registered in a REDCap database (cohort 2). The outcomes of the two cohorts were compared. RESULTS: A total of 314 patients underwent surgery in our institution from 2007 and 2021: 7.5 patients/year in cohort 1 (retrospective, 2007-2016) and 40.8 patients/year in cohort 2 (after network creation, 2017-2021). Median disease-free survival was increased from 16.5 months (range 13.2-20.4) in cohort 1 to 27.1 months (range 21.5-33.2) in cohort 2 (p=0.0004). In cohort 2, the rate of patients with residual disease at the end of the surgery was significantly less (18.7% vs 8.8%, p=0.023), although more patients in cohort 1 received neoadjuvant chemotherapy (89% vs 54%, p<0.001). However, there was a higher rate of complications in the patients in cohort 2 (18.8% vs 30%, p=0.041). CONCLUSION: Our study shows that, with the help of ESGO and its recommendations, we have been able to create an efficient advanced ovarian cancer centralized network and this may provide an improvement in the quality of care.

Outcomes after Laparoscopic Excision of Bladder Endometriosis Using a CO2 Laser: A Review of 207 Cases in a Single Center.

STUDY OBJECTIVE: Assess efficacy, safety, fertility outcomes and recurrence after laparoscopic resection of bladder endometriosis (BE) using a CO2 laser. DESIGN: Retrospective cohort study. SETTINGS: University gynecologic surgery unit, referral center for endometriosis. PATIENTS: A total of 207 women having undergone laparoscopic BE excision between January 1998 and January 2019. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Intra- and postoperative complication rates. Disease recurrence and fertility outcomes in patients with a minimum 1-year follow-up (n = 176) for "isolated" and "non-isolated" BE groups. RESULTS: Forty-three patients presented with isolated BE. Bladder "shaving" without mucosae opening was performed in 50.7% cases. No intraoperative complications were noted. One postoperative grade 3 complication was related to BE excision: a bladder breach requiring closure by repeat laparoscopy. Mean (± SD) follow-up was 7.05 (± 4.65) years. In patients wishing to conceive (n = 132), the total pregnancy rate (PR) was 75% (48.5% spontaneous), 76.19% in the isolated BE group (56.3% spontaneous). Among the 94 patients with previous infertility, 74.5% conceived, 50% spontaneously. No statistical difference was found in PR and need for in vitro fertilization between isolated and nonisolated BE groups. BE recurrence rate was 3.4%. No difference was observed between groups with full-thickness bladder resection (4/88) and shaving (2/88) (p = .406). Age at surgery (hazard ratio 0.91 [0.84-0.98], p = .016) and postoperative pregnancy (hazard ratio 0.07 [0.01-0.91], p = .042) showed influence on disease recurrence. CONCLUSIONS: The study demonstrates that laparoscopic BE removal is feasible with very low complications rates and was associated with high PR (both spontaneous and in vitro fertilization), even in patients with previous infertility. BE recurrence is lower than for other endometriosis locations. Bladder endometriosis; Laparoscopy; Deep infiltrating endometriosis; Fertility; Partial bladder resection.

Long-term follow-up of vitrified and autografted baboon (Papio anubis) ovarian tissue.

STUDY QUESTION: Can vitrified baboon ovarian tissue survive >5 months after autotransplantation and subsequently restore fertility? SUMMARY ANSWER: Our results show that ovarian tissue grafts can survive at least 18 months, but fertility restoration could not be confirmed due to lack of pregnancy. WHAT IS KNOWN ALREADY: Ovarian function in baboons can be re-established after autografting of vitrified-warmed ovarian tissue fragments. STUDY DESIGN, SIZE, DURATION: Ovaries from five adult female baboons were used for this study. Unilateral ovariectomy was performed in each animal, followed by vitrification of ovarian fragments. Orthotopic autotransplantation of the vitrified-warmed ovarian fragments was carried out 1 day after ovariectomy. One month later, the other ovary was removed from each animal and vitrified. The next day, the ovarian samples were warmed and orthotopically autografted. Biopsies of grafted tissues were taken after 12 and 18 months for stromal tissue and follicle evaluation. Control samples were collected before vitrification. PARTICIPANTS/MATERIALS, SETTING, METHODS: After grafting, follicle survival, growth and function and also the quality of stromal tissue were assessed histologically and by immunohistochemistry. Estrogen levels were measured, and cyclicity was monitored. All five animals were mated several times. Male baboons used in the mating experiments were not of proven fertility. MAIN RESULTS AND THE ROLE OF CHANCE: After vitrification, warming and long-term grafting, follicles were able to grow. However, their function may have been negatively affected by vitrification and/or transplantation, as expression of kit ligand and c-kit differed from fresh ungrafted tissue (P < 0.05). Corpora lutea and/or ovulation stigma were observed in grafts, indicating successful ovulation in all the baboons, with estrogen levels comparable to those in adult female baboons. LARGE SCALA DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION: Despite our promising findings on ovarian function restoration, the vitrification procedure could not be validated. Moreover, male baboons used for mating were not of proven fertility. WIDER IMPLICATIONS OF THE FINDINGS: Our protocol of ovarian tissue vitrification successfully re-established ovarian function in a baboon model of autotransplantation. While more studies are required to determine whether this approach can indeed restore fertility, it may prove an easy way of cryopreserving ovarian tissue with a view to recovering ovarian function. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the Fonds National de la Recherche Scientifique (FNRS) (C.A.A. is an FRS-FNRS Research Associate; grant 5/4/150/5 awarded to M.M.D.), Fonds Spéciaux de Recherche, Fondation Saint Luc, Stichting tegen Kanker (Fondation contre le Cancer), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil; grant # 013/14 CAPES/WBI awarded to C.M.L.), Wallonie-Bruxelles International (awarded to C.A.A.), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq; grant awarded to Sarah R. Scalercio) and donations from the Ferrero family. None of the authors have any competing interests to declare.

Restoring the association of the T cell receptor with CD8 reverses anergy in human tumor-infiltrating lymphocytes.

For several days after antigenic stimulation, human cytolytic T lymphocyte (CTL) clones exhibit a decrease in their effector activity and in their binding to human leukocyte antigen (HLA)-peptide tetramers. We observed that, when in this state, CTLs lose the colocalization of the T cell receptor (TCR) and CD8. Effector function and TCR-CD8 colocalization were restored with galectin disaccharide ligands, suggesting that the binding of TCR to galectin plays a role in the distancing of TCR from CD8. These findings appear to be applicable in vivo, as TCR was observed to be distant from CD8 on human tumor-infiltrating lymphocytes, which were anergic. These lymphocytes recovered effector functions and TCR-CD8 colocalization after ex vivo treatment with galectin disaccharide ligands. The separation of TCR and CD8 molecules could be one major mechanism of anergy in tumors and other chronic stimulation conditions.

European Renal Best Practice Guideline on kidney donor and recipient evaluation and perioperative care.

The European Best Practice Guideline group (EBPG) issued guidelines on the evaluation and selection of kidney donor and kidney transplant candidates, as well as post-transplant recipient care, in the year 2000 and 2002. The new European Renal Best Practice board decided in 2009 that these guidelines needed updating. In order to avoid duplication of efforts with kidney disease improving global outcomes, which published in 2009 clinical practice guidelines on the post-transplant care of kidney transplant recipients, we did not address these issues in the present guidelines.The guideline was developed following a rigorous methodological approach: (i) identification of clinical questions, (ii) prioritization of questions, (iii) systematic literature review and critical appraisal of available evidence and (iv) formulation of recommendations and grading according to Grades of Recommendation Assessment, Development, and Evaluation (GRADE). The strength of each recommendation is rated 1 or 2, with 1 being a 'We recommend' statement, and 2 being a 'We suggest' statement. In addition, each statement is assigned an overall grade for the quality of evidence: A (high), B (moderate), C (low) or D (very low). The guideline makes recommendations for the evaluation of the kidney transplant candidate as well as the potential deceased and living donor, the immunological work-up of kidney donors and recipients and perioperative recipient care.All together, the work group issued 112 statements. There were 51 (45%) recommendations graded '1', 18 (16%) were graded '2' and 43 (38%) statements were not graded. There were 0 (0%) recommendations graded '1A', 15 (13%) were '1B', 19 (17%) '1C' and 17 (15%) '1D'. None (0%) were graded '2A', 1 (0.9%) was '2B', 8 (7%) were '2C' and 9 (8%) '2D'. Limitations of the evidence, especially the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research.We present here the complete recommendations about the evaluation of the kidney transplant candidate as well as the potential deceased and living donor, the immunological work-up of kidney donors and recipients and the perioperative recipient care. We hope that this document will help caregivers to improve the quality of care they deliver to patients. The full version with methods, rationale and references is published in Nephrol Dial Transplant (2013) 28: i1-i71; doi: 10.1093/ndt/gft218 and can be downloaded freely from http://www.oxfordjournals.org/our_journals/ndt/era_edta.html.

IRF4 impedes human CD8 T cell function and promotes cell proliferation and PD-1 expression.

Human CD8 tumor-infiltrating lymphocytes (TILs) with impaired effector functions and PD-1 expression are categorized as exhausted. However, the exhaustion-like features reported in TILs might stem from their activation rather than the consequence of T cell exhaustion itself. Using CRISPR-Cas9 and lentiviral overexpression in CD8 T cells from non-cancerous donors, we show that the T cell receptor (TCR)-induced transcription factor interferon regulatory factor 4 (IRF4) promotes cell proliferation and PD-1 expression and hampers effector functions and expression of nuclear factor κB (NF-κB)-regulated genes. While CD8 TILs with impaired interferon γ (IFNγ) production exhibit activation markers IRF4 and CD137 and exhaustion markers thymocyte selection associated high mobility group box (TOX) and PD-1, activated T cells in patients with COVID-19 do not demonstrate elevated levels of TOX and PD-1. These results confirm that IRF4+ TILs are exhausted rather than solely activated. Our study indicates, however, that PD-1 expression, low IFNγ production, and active cycling in TILs are all influenced by IRF4 upregulation after T cell activation.

Intraoperative Ketorolac and Outcomes after Ovarian Cancer Surgery.

INTRODUCTION: Surgery is the cornerstone of ovarian cancer treatment. However, surgery and perioperative inflammation have been described as potentially pro-metastagenic. In various animal models and other human cancers, intraoperative administration of non-steroidal anti-inflammatory drugs (NSAIDs) appears to have a positive impact on patient outcomes. MATERIALS AND METHODS: In this unicentric retrospective study, we provide an exploratory analysis of the safety and potential benefit of intraoperative administration of ketorolac on the outcome of patients undergoing surgery for ovarian cancer. The study population included all patients who were given a diagnosis of ovarian, fallopian tube or peritoneal cancer by the multidisciplinary oncology committee (MOC) of the Cliniques universitaires Saint-Luc between 2015 and 2020. RESULTS: We included 166 patients in our analyses, with a median follow-up of 21.8 months. Both progression-free survival and overall survival were superior in patients who received an intraoperative injection of ketorolac (34.4 months of progression-free survival in the ketorolac group versus 21.5 months in the non-ketorolac group (p = 0.002), and median overall survival was not reached in either group but there was significantly higher survival in the ketorolac group (p = 0.004)). We also performed subgroup analyses to minimise bias due to imbalance between groups on factors that could influence patient survival, and the group of patients receiving ketorolac systematically showed a better outcome. Uni- and multivariate analyses confirmed that administration of ketorolac intraoperatively was associated with better progression-free survival (HR = 0.47 on univariate analysis and 0.43 on multivariate analysis, p = 0.003 and 0.023, respectively). In terms of complications, there were no differences between the two groups, either intraoperatively or postoperatively. CONCLUSION: Our study has shown a favourable association between the use of ketorolac during surgery and the postoperative progression of ovarian cancer in a group of 166 patients, without any rise in intra- or postoperative complications. These encouraging results point to the need for a prospective study to confirm the benefit of intraoperative administration of ketorolac in ovarian cancer surgery.

Laparoscopic repair of post-cesarean section uterine scar defects diagnosed in nonpregnant women.

Herein we describe laparoscopic repair of uterine scar defects after cesarean section and pregnancy outcomes in a series of 13 patients. Defects and the residual anterior uterine wall were evaluated using ultrasound and magnetic resonance imaging (MRI). Patients' clinical symptoms were recorded. Pregnancy outcomes were investigated after laparoscopic surgical repair. Intervention included laparoscopic repair of the defect, including excision of fibrotic tissue and laparoscopic closure of the anterior uterine wall. The defect was completely corrected using this technique in all 13 patients. Four patients became pregnant spontaneously, 3 delivered via cesarean section between 38 and 39 weeks, and 1 is currently pregnant. Evaluation of uterine scar defects after cesarean section can be performed using ultrasound and MRI, and the defect can be repaired via laparoscopy, with reproducible postoperative anatomic and functional outcomes.

A review of 15 years of ovarian tissue bank activities.

PURPOSE: To review 15 years of activities in ovarian tissue cryobanking from medical database files, including patient indications, histological evaluation and clinical characteristics. METHODS: Retrospective longitudinal analysis of data from an ovarian tissue bank in an academic hospital. Five hundred and eighty-two patients had their ovarian tissue cryobanked between April 1997 and January 2012. Analysis of cryobanking database: precryopreservation patient characteristics, indications and safety issues, laboratory files and postcryopreservation clinical data. RESULTS: Of the 582 patients who had their ovarian tissue cryopreserved, 106 patients donated for research purposes and 476 patients for fertility preservation and long-term cryopreservation. Clinical data analysis of the 476 patients revealed a mean age at the time of cryopreservation of 23 ± 8.5 years (range: 9 months - 39 years), with 96.2 % of subjects aged ≤35 years (n = 458). Among 391 cases of malignant disease, hematological malignancies (39.9 %, n = 156) and breast cancer (21.7 %, n = 85) were the two main indications. At histology, malignant cells were found in ovarian tissue from leukemia patients (n = 3) and non-Hodgkin's lymphoma patients (n = 2). Eleven patients underwent autotransplantation, resulting in 5 live births and 1 ongoing pregnancy. CONCLUSION: This is the largest and most comprehensive study to describe and analyze indications and clinical patient characteristics before and after ovarian tissue cryopreservation. The procedure is safe, easy and promising. The database concept is a useful tool in patient selection for autotransplantation.

Profile of Linzagolix in the Management of Endometriosis, Including Design, Development and Potential Place in Therapy: A Narrative Review.

Estrogens play a critical role in the pathogenesis of endometriosis and it is logical to assume that lowering estradiol levels with oral gonadotropin-releasing hormone (GnRH) antagonists may prove effective, especially in women who fail to respond to progestogens. Indeed, due to progesterone resistance, oral contraceptives and progestogens work well in two-thirds of women suffering from endometriosis, but are ineffective in 33% of women. Oral GnRH antagonists have therefore been evaluated for management of premenopausal women with endometriosis-associated pelvic pain. The first publication on these drugs reported the efficacy of elagolix. The present paper is a narrative review of linzagolix, which is an orally administered GnRH receptor antagonist with low pharmacokinetic/pharmacodynamic variability. It binds to and blocks the GnRH receptor in the pituitary gland, resulting in a dose-dependent drop in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) production. This reduction in LH and FSH levels in turn leads to a dose-dependent decline in estrogen. Phase 2 and 3 trials are reviewed and discussed here. There is a place for GnRH antagonists in the management of symptomatic endometriosis, and linzagolix with or without add-back therapy (ABT) is one option that can be used at low doses, avoiding the need for ABT, which is contraindicated in some patients.

Follicle outcomes in human ovarian tissue: effect of freezing, culture, and grafting.

OBJECTIVE: To study the effect of freezing, in vitro culture (IVC) and grafting to chorioallantoic membrane (CAM) on follicle outcomes in human ovarian tissue. DESIGN: An experimental study. SETTING: University-based research laboratory. PATIENTS: Fresh and cryopreserved ovarian tissue from 10 patients was donated to research with their consent and institutional review board approval. INTERVENTIONS: Fresh and frozen-thawed ovarian cortical pieces were in vitro-cultured and compared (fresh-IVC vs FT-IVC). The FT-IVC fragments were then examined against fragments grafted to CAM (FT-CAM). After both IVC and CAM grafting, ovarian cortical pieces (4×2×1 mm3) were analyzed on days 0, 1, and 6. MAIN OUTCOME MEASURES: Follicle analyses included histology (count and classification) and immunohistochemistry (Ki67 [proliferation], caspase-3 [apoptosis], 1A and 1B light chain 3B [autophagy], p-Akt, FOXO1, and p-rpS6 [PI3K activation]). Droplet digital polymerase chain reaction further explored expression of PI3K pathway- and oocyte-related genes in tissue sections. RESULTS: No major differences were detected between fresh-IVC and FT-IVC tissues in any conducted analyses. Although a significant drop was observed in primordial follicle (PF) proportions in the fresh-IVC and FT-IVC groups (d0 vs. d6, P<.002), they held steady in the FT-CAM group (d0 vs. d6, P>.05). The PF rates were also significantly higher in the FT-CAM group than the FT-IVC group on d6 (P=.02). Importantly, avian erythrocytes were already present in 30% of implants from d1. Apoptotic and autophagic follicle rates increased during IVC (P<.008), but remained significantly lower in the FT-CAM group (P<.01), confirming superior follicle preservation in CAM-grafted tissue. Upregulation of the PI3K/FOXO pathway was established in the IVC groups, demonstrating PF activation, whereas significant pathway downregulation was detected in the FT-CAM group (P<.03). The droplet digital polymerase chain reaction tests confirmed oocyte growth during IVC and follicle autophagy in all groups; however, the PI3K pathway appeared to be differentially modulated in tissues and follicles. CONCLUSIONS: In vitro culture induces PF depletion with no additional impact of freezing. Grafting to CAM preserves the PF pool by curbing follicle activation, apoptosis, and autophagy, probably thanks to rapid graft revascularization and/or the circulating embryonic antimüllerian hormone. These findings highlight the importance of enhancing neoangiogenesis in ovarian grafts and investigating the potential benefits of administering antimüllerian hormone to prevent PF burnout.

Hysteroscopic management of molar pregnancy: A series of 36 cases.

Background: Hydatidiform Mole (HM) is the most common form of gestational trophoblastic disease. Dilatation and curettage is the classical treatment of this affection. Hysteroscopic resection (HsR) is an alternative for the treatment of intra-uterine pathology. Objective: To describe the feasibility of HsR for the management of HM. Result: Case series of patients who had a complete or partial HM confirmed by histological examination of the trophoblastic tissue resected by operative hysteroscopy between 2007 and 2019. After approval of our ethics committee, we evaluated 36 patients who underwent hysteroscopic resection for molar pregnancy. Histological analysis showed partial HM in 28 patients (77.8%) and complete HM in 8 (22.2%). Main surgical complications were uterine perforation in one patient and glycine resorption in 10 patients with two cases of hyponatremia corrected by standard treatment. We performed an ultrasound control 1 month after the intervention in 19 patients (52.8%) as they had slow decrease of HCG or bleeding complaints and found retained product of conception (RPOC) in six patients (16.7%). Conclusion: This first report on a small number of patients demonstrate that hysteroscopic resection is a feasible procedure for the management of molar pregnancy. Direct visualization of the procedure helps the surgeon to control the resection. Further studies are mandatory to compare this technique with D&C in term of RPOC and fertility outcomes as it remains the standard treatment.

HELIOS-expressing human CD8 T cells exhibit limited effector functions.

Introduction: The transcription factor HELIOS is primarily known for its expression in CD4 regulatory T cells, both in humans and mice. In mice, HELIOS is found in exhausted CD8 T cells. However, information on human HELIOS+ CD8 T cells is limited and conflicting. Methods: In this study, we characterized by flow cytometry and transcriptomic analyses human HELIOS+ CD8 T cells. Results: These T cells primarily consist of memory cells and constitute approximately 21% of blood CD8 T cells. In comparison with memory HELIOS- T-BEThigh CD8 T cells that displayed robust effector functions, the memory HELIOS+ T-BEThigh CD8 T cells produce lower amounts of IFN-γ and TNF-α and have a lower cytotoxic potential. We wondered if these cells participate in the immune response against viral antigens, but did not find HELIOS+ cells among CD8 T cells recognizing CMV peptides presented by HLA-A2 and HLA-B7. However, we found HELIOS+ CD8 T cells that recognize a CMV peptide presented by MHC class Ib molecule HLA-E. Additionally, a portion of HELIOS+ CD8 T cells is characterized by the expression of CD161, often used as a surface marker for identifying TC17 cells. These CD8 T cells express TH17/TC17-related genes encoding RORgt, RORa, PLZF, and CCL20. Discussion: Our findings emphasize that HELIOS is expressed across various CD8 T cell populations, highlighting its significance beyond its role as a transcription factor for Treg or exhausted murine CD8 T cells. The significance of the connection between HELIOS and HLA-E restriction is yet to be understood.

Machine perfusion or cold storage in deceased-donor kidney transplantation.

BACKGROUND: Static cold storage is generally used to preserve kidney allografts from deceased donors. Hypothermic machine perfusion may improve outcomes after transplantation, but few sufficiently powered prospective studies have addressed this possibility. METHODS: In this international randomized, controlled trial, we randomly assigned one kidney from 336 consecutive deceased donors to machine perfusion and the other to cold storage. All 672 recipients were followed for 1 year. The primary end point was delayed graft function (requiring dialysis in the first week after transplantation). Secondary end points were the duration of delayed graft function, delayed graft function defined by the rate of the decrease in the serum creatinine level, primary nonfunction, the serum creatinine level and clearance, acute rejection, toxicity of the calcineurin inhibitor, the length of hospital stay, and allograft and patient survival. RESULTS: Machine perfusion significantly reduced the risk of delayed graft function. Delayed graft function developed in 70 patients in the machine-perfusion group versus 89 in the cold-storage group (adjusted odds ratio, 0.57; P=0.01). Machine perfusion also significantly improved the rate of the decrease in the serum creatinine level and reduced the duration of delayed graft function. Machine perfusion was associated with lower serum creatinine levels during the first 2 weeks after transplantation and a reduced risk of graft failure (hazard ratio, 0.52; P=0.03). One-year allograft survival was superior in the machine-perfusion group (94% vs. 90%, P=0.04). No significant differences were observed for the other secondary end points. No serious adverse events were directly attributable to machine perfusion. CONCLUSIONS: Hypothermic machine perfusion was associated with a reduced risk of delayed graft function and improved graft survival in the first year after transplantation. (Current Controlled Trials number, ISRCTN83876362.)

Outcome of the living kidney donor.

Renal transplantation from living kidney donors is still relatively marginal in most of the European countries. However, this source of kidney grafts may help to overcome in part the organ donor shortage of cadaveric donors. The living donor strategy implies correct and objective information about donation risks and completely free acceptance of the living candidate of the donation. In this paper, we reviewed the consequences of kidney donation on the living donor health, considering very short term (linked to the surgery), short term (effect of nephrectomy on glomerular filtration rate) and long term (risk of mortality, chronic kidney disease, proteinuria and hypertension) consequences of kidney donation.

Machine perfusion versus cold storage for the preservation of kidneys from donors ≥ 65 years allocated in the Eurotransplant Senior Programme.

BACKGROUND: In the Eurotransplant Senior Programme (ESP), kidneys from donors aged ≥ 65 years are preferentially allocated locally and transplanted into patients aged ≥ 65 years on dialysis. The purpose of this study was to analyse whether the results of transplantation in the ESP can be improved by preservation of organs by hypothermic machine perfusion (MP) compared with simple cold storage (CS). METHODS: Overall, 85 deceased heart-beating donors ≥ 65 years of age were included in this analysis with follow-up until 1 year post-transplant. For each donor, one kidney was randomly assigned to preservation by CS and the contralateral kidney to MP from organ procurement until transplantation. Delayed graft function (DGF), primary non-function (PNF) and 1-year patient and graft survival rates were evaluated as primary and secondary endpoints. RESULTS: The median recipient age was 66 years in both groups and the median cold ischaemia time was 11 h for MP and 10.5 h for CS (P = 0.69). The DGF rate was 29.4% for MP and 34.1% for CS (P = 0.58). Only extended duration of cold ischaemia time was an independent risk factor for the development of DGF (odds ratio 1.2, P < 0.0001). PNF was significantly reduced (3.5% MP versus 12.9% CS, P = 0.02). The 1-year patient and graft survival rates were similar for MP and CS (94% versus 95% and 89 versus 81%, P > 0.05). The 1-year graft survival rate was significantly improved after MP in recipients who developed DGF (84% MP versus 48% CS, P = 0.01). CONCLUSIONS: Continuous pulsatile hypothermic MP for kidneys from donors aged ≥ 65 years can reduce the rate of never-functioning kidneys and improve the 1-year graft survival rate of kidneys with DGF. In this small cohort, the known advantage of MP for the reduction of DGF could not be confirmed, possibly due to relatively short cold ischaemia times.

Osteomyelitis pubis caused by Kingella kingae in an adult patient: report of the first case.

BACKGROUND: Kingella kingae is the second most common pathogen causing paediatric arthritis and is described to be the causative bacteria in some paediatric osteomyelitis. Its microbiological detection is particularly difficult due to its slow growing. To our best knowledge this is the first case description of osteomyelitis pubis caused by this microorganism. CASE PRESENTATION: We report the unusual case of pubic osteomyelitis with soft tissue abcess caused by Kingella kingae in an adult patient of 66 years with a history of end-stage renal disease and breast carcinoma. Diagnosis was based on imaging and the microorganism was isolated from Computed Tomography-guided aspiration of synovial fluid. The infection resolved completely after twelve weeks of treatment with oral amoxicillin. CONCLUSION: This case description highlights the importance in osteoarticular infections of systematic inoculation of synovial liquid in BACTEC vials to optimise the detection of causative organisms, which can necessitate specific treatments.

Results of kidney transplantation from controlled donors after cardio-circulatory death: a single center experience.

The aim of this study was to determine results of kidney transplantation (KT) from controlled donation after cardio-circulatory death (DCD). Primary end-points were graft and patient survival, and post-transplant complications. The influence of delayed graft function (DGF) on graft survival and DGF risk factors were analyzed as secondary end-points. This is a retrospective mono-center review of a consecutive series of 59 DCD-KT performed between 2005 and 2010. Overall graft survival was 96.6%, 94.6%, and 90.7% at 3 months, 1 and 3 years, respectively. Main cause of graft loss was patient's death with a functioning graft. No primary nonfunction grafts. Renal graft function was suboptimal at hospital discharge, but nearly normalized at 3 months. DGF was observed in 45.6% of all DCD-KT. DGF significantly increased postoperative length of hospitalization, but had no deleterious impact on graft function or survival. Donor body mass index ≥30 was the only donor factor that was found to significantly increase the risk of DGF (P < 0.05). Despite a higher rate of DGF, controlled DCD-KT offers a valuable contribution to the pool of deceased donor kidney grafts, with comparable mid-term results to those procured after brain death.

Kidney donation after circulatory death in a country with a high number of brain dead donors: 10-year experience in Belgium.

Worldwide shortage of standard brain dead donors (DBD) has revived the use of kidneys donated after circulatory death (DCD). We reviewed the Belgian DCD kidney transplant (KT) experience since its reintroduction in 2000. Risk factors for delayed graft function (DGF) were identified using multivariate analysis. Five-year patient/graft survival was assessed using Kaplan-Meier curves. The evolution of the kidney donor type and the impact of DCDs on the total KT activity in Belgium were compared with the Netherlands. Between 2000 and 2009, 287 DCD KT were performed. Primary nonfunction occurred in 1% and DGF in 31%. Five-year patient and death-censored graft survival were 93% and 95%, respectively. In multivariate analysis, cold storage (versus machine perfusion), cold ischemic time, and histidine-tryptophan-ketoglutarate solution were independent risk factors for the development of DGF. Despite an increased number of DCD donations and transplantations, the total number of deceased KT did not increase significantly. This could suggest a shift from DBDs to DCDs. To increase KT activity, Belgium should further expand controlled DCD programs while simultaneously improve the identification of all potential DBDs and avoid their referral for donation as DCDs before brain death occurs. Furthermore, living donation remains underused.

A multicenter, randomized, double-blind study comparing different FK778 doses (manitimus) with tacrolimus and steroids vs. MMF with tacrolimus and steroids in renal transplantation.

BACKGROUND: This multicenter phase II study in renal transplantation compared 3 concentration-controlled ranges of FK778 (manitimus) with mycophenolate mofetil (MMF) both given in combination with tacrolimus and corticosteroids. METHODS: 364 patients were randomized to 12-month treatment: high-level FK778 group (H, N=87) received 4 x 600 mg/day (4 days) followed by 120 mg/day; mid-level FK778 group (M, N=92) received 3 x 600 mg/day (3 days) followed by 110 mg/day, low-level FK778 group (L, N=92) received 2 x 600 mg/day (2 days) followed by 100 mg/day, and control group received MMF 1 g/day (MMF, N=93). After week 6, FK778 doses were adjusted to trough ranges of 75-125 µg/mL (H), 50-100 µg/mL (M) and 25-75 µg/mL (L). Tacrolimus and steroids were administered at the same dose in each of the 4 groups. RESULTS: Biopsy proven acute rejection (BPAR) at 24 weeks, the primary study endpoint, was comparable in the L (22.8%) and MMF (17.2%) groups but higher in the H (34.5%) and M (29.3%) groups. BPAR at 12 months was comparable in the L (23.9%) and MMF (19.4%) groups but higher in the H (34.5%) and M (31.5%) groups. Graft and patient survival were lowest in the H group and renal function was poorest in the H and M groups. Premature study withdrawal was highest in the H group. CONCLUSIONS: Efficacy was similar between the low-level FK778 and MMF groups. Increased FK778 exposure was poorly tolerated and did not improve efficacy.