Permanent Polymer Coating for in vivo MRI Visualization of Tissue Reinforcement Prostheses

The clinical advantage of MRI visualization of prostheses in soft tissue prolapses is very appealing as over 1?000?000 MRI-transparent synthetic meshes are implanted annually, and postoperative complications such as mesh shrinkage and migration are frequent. Here, the synthesis of a new material composed of a DTPA-Gd complex grafted onto a backbone of PMA via a covalent bond is described (DTPA-Gd-PMA). This new polymer is sprayed onto meshes and gives an MR signal for a long period without any significant release of Gd. In vitro cytocompatibility tests on fibroblasts show limited cytotoxicity. Microscopic investigations indicate that vital cells rapidly colonize the material. Finally, coated meshes implanted in rats are easily recognizable using an MR imaging system

Proenkephalin A 119-159 (Penkid) Is an Early Biomarker of Septic Acute Kidney Injury: The Kidney in Sepsis and Septic Shock (Kid-SSS) Study

Introduction: Sepsis is the leading cause of acute kidney injury (AKI) in critically ill patients. The Kidney in Sepsis and Septic Shock (Kid-SSS) study evaluated the value of proenkephalin A 119-159 (penkid)—a sensitive biomarker of glomerular function, drawn within 24 hours upon intensive care unit (ICU) admission and analyzed using a chemiluminescence immunoassay—for kidney events in sepsis and septic shock. Methods: The Kid-SSS study was a substudy of Adrenomedullin and Outcome in Severe Sepsis and Septic Shock (AdrenOSS) (NCT02393781), a prospective, observational, multinational study including 583 patients admitted to the intensive care unit with sepsis or septic shock and a validation cohort of 525 patients from the French and euRopean Outcome reGistry in Intensive Care Units (FROG-ICU) study. The primary endpoint was major adverse kidney events (MAKEs) at day 7, composite of death, renal replacement therapy, and persistent renal dysfunction. The secondary endpoints included AKI, transient AKI, worsening renal function (WRF), and 28-day mortality. Results: Median age was 66 years (interquartile range 55–75), and 28-day mortality was 22% (95% confidence interval [CI] 19%−25%). Of the patients, 293 (50.3%) were in shock upon ICU admission. Penkid was significantly elevated in patients with MAKEs, persistent AKI, and WRF (median = 65 [IQR = 45–106] vs. 179 [114–242]; 53 [39–70] vs. 133 [79–196] pmol/l; and 70 [47–121] vs. 174 [93–242] pmol/l, all P < 0.0001), also after adjustment for confounding factors (adjusted odds ratio = 3.3 [95% CI = 1.8–6.0], 3.9 [95% CI = 2.1–7.2], and 3.4 [95% CI = 1.9–6.2], all P < 0.0001). Penkid increase preceded elevation of serum creatinine with WRF and was low in renal recovery. Conclusion: Admission penkid concentration was associated with MAKEs, AKI, and WRF in a timely manner in septic patients

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

BACKGROUND: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. METHODS: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. RESULTS: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). CONCLUSIONS: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02393781 . Registered on March 19, 2015

Prévention et traitement des synéchies endo-utérines : revue de la littérature

International audienceIntra-uterine adhesions are a major cause of secondary infertility. The prevalence of adhesions is probably underestimated due to the heterogeneity of the symptoms. An exhaustive literature search using search engines MEDLINE, Pubmed, Cochrane library and Web of Science was performed to make a focus on the origins, consequences and methods of prevention of intra-uterine adhesions. Intra-uterine adhesions are likely to occur after any endo-uterine surgery via dysregulated activation of coagulation chain linked to the inflammatory process. Early and late obstetric complications are also recognized as caused by adhesions. The diagnosis is currently performed by hysteroscopy but it remains an invasive procedure even if it can be done with an ambulatory management. Several research approaches inspired by intra-abdominal surgery for the prevention of pelvic adhesions have been developed. However, no current method of prevention has proven its effectiveness in terms of improving spontaneous fertility. The improvement in surgical practices, the design of new intra-uterine medical devices and new research especially in the field of endometrial stem cells can maybe reduce the rate of adhesions end their complications after intra-uterine surgery

Quelles mesures de protection périnéale à l’accouchement sont consensuelles en France ? Résultats d’une enquête Delphi

International audienceOBJECTIVE:To evaluate expert's opinion in order to obtain a consensus on the different measures of perineal protection at the time of vaginal delivery.METHODS:A survey using the Delphi method was carried out with a panel of French obstetricians, urogynecologists and midwives. The questionnaire included 22 questions grouped into four groups: expulsive efforts, indications of episiotomy, episiotomy repair and other forms of perineal protection. The experts had to answer on a 9-point scale, both on the validity and the clarity of each proposal. After analysis of the replies of the first round, a second round was sent to the same experts for certain proposals. Each turn was the subject of two raises. To be validated, each proposal had to obtain a median equal to or greater than 7/9 and an agreement between the experts greater than 65% in the first round, and more than 75% in the second round.RESULTS:The study was conducted between March and October 2016. Of the 300 experts initially selected, 93 (31%) responded to the first round, including 63 obstetricians (67.7%), 12 urogynecologists (12.9%) and 18 midwives (19.4%). In the second round, 72 experts replied, representing 77.4% of the experts who also answered the first round. At the end of the two rounds, 11 proposals were validated, and 11 rejected. The following recommendations have been validated. Uterine expression should be proscribed. The two modes of pushing (blocked in Valsalva and by blowing) can be indifferently proposed, in case of fetal progression and in the absence of fetal distress. The midline episiotomy should be proscribed. The medio-lateral (or lateral) episiotomy should be left to the discretion of the accoucheur. The maintenance of the fetal head with one hand must be systematic to the expulsion to protect the perineum. Repair of the episiotomy should be made (except in some cases) with a rapid absorbable suture. The prescription of NSAIDs and/or painkillers of level 2 should be preferred to reduce the pain of post-natal perineal scars.CONCLUSION:Several measures of perineal protection at the time of vaginal delivery are consensual in France. Other measures should be studied further.LEVEL OF EVIDENCE:4

E-learning et simulation en échographie focalisée pour la formation continue des sages-femmes en salle de naissance

International audienceObjective: To evaluate a training program in limited obstetric ultrasound, combining e-learning and simulation.Methods: This a descriptive cohort study in Single-center study conducted in a French university hospital. Thirty-three practicing midwives who had not received basic training in ultrasonography had unlimited access to an e-learning platform offering interactive theoretical instruction modules. Then, they attended a one-day simulator-based obstetric ultrasound workshop. A theoretical competency test was taken before the e-learning component (T1), then before (T2) and after (T3) the simulation workshop. Their competency in specific practical tasks was assessed before and after the workshop. A learner satisfaction questionnaire was completed after the program.Results: The mean score obtained in the theoretical competency test was 46.6% (range 8.3-83.3%) at T1, 87.2% (66.6-100%) at time T2, and 91.6% (66.6-100%) at T3. Significant improvements were observed between times T1 and T2 (P<0.001) or T3 (P<0.001), as well as in the performance of certain practical tasks, such as placental location (P=0.02) and visualization of the cervix (P=0.03). The mean number of logins to the e-learning platform during the program was 11.2 per participant (6-24). Most participants were satisfied with the training and reported an improvement in their daily practice.Conclusion: Training in limited obstetric ultrasound, combining e-learning to acquire theoretical knowledge and a hands-on simulation workshop, appears to meet the needs of practicing midwives. Most participants were satisfied with the proposed teaching and the rapid acquisition of ultrasound skills applicable to their clinical practice.Keywords: Education; Limited obstetric ultrasound; Midwife; Obstetrics; Obstétrique; Simulation; e-learning; Échographie focalisée; Éducation

[Natural cycle for frozen-thawed embryo transfer: Spontaneous ovulation or triggering by HCG]

International audienceOBJECTIVE: To compare frozen-thawed embryo transfer (FET) outcomes in natural cycles according to ovulation induction: spontaneous versus recombinant human chorionic gonadotrophin (r-hCG) triggering. METHODS: This retrospective study included all patients monitored for natural cycle FET during one year. When serial monitoring were performed until spontaneous LH rise, patients were included in group A (n=38) whereas those receiving r-hCG for ovulation triggering formed group B (n=43). All embryos had been cryopreserved by a vitrification method following a previous IVF cycle. No luteal phase support had been given. We compared outcomes between the 2 groups. RESULTS: After checking groups comparability, we didn't find significant difference for the implantation rate, clinical pregnancy rate and live birth (31% vs 45%, 32% vs 51% et 21% vs 32%, respectively for group A and B). The number of monitoring was significantly lower in group B (1,9\textpm0,8 versus 2,5\textpm1, P=0,006). DISCUSSION: Although no consensus has been yet established, natural cycle seems indicated for normo-ovulating patients but the question of ovulation induction is still debated. In our study, triggering ovulation by r-hCG, respecting strict criteria, seems provide good results while reducing both protocol's constraints and cost

Cranberry capsules to prevent nosocomial urinary tract bacteriuria after pelvic surgery: a randomised controlled trial

International audienceOBJECTIVE:To evaluate whether cranberries are able to prevent postoperative urinary bacteriuria in patients undergoing pelvic surgery and receiving transurethral catheterisation.DESIGN:Randomised, double-blind, placebo-controlled trial.SETTINGS:French tertiary Care centre, University Hospital.POPULATION:A total of 272 women undergoing pelvic surgery aged 18 or older.METHODS:Participants undergoing pelvic surgery were randomised to 36 mg cranberry (proanthocyanidins, PAC) or placebo once daily for 10 days. Statistical analysis was performed by a chi-square test.MAIN OUTCOME MEASURES:The primary and secondary outcomes were postoperative bacteriuria, defined by a positive urine culture, within the first 15 and 40 days, respectively.RESULTS:Two hundred and fifty-five participants received the intended treatment: 132 (51.8%) received PAC and 123 (48.2%) received placebo. There were no significant differences in baseline demographics, intra-operative characteristics or duration and type of catheterisation between the two groups. PAC prophylaxis did not reduce the risk of bacteriuria treatment within 15 days of surgery [27% bacteriuria with PAC compared with 25% bacteriuria with placebo: relative risk 1.05, 95% CI 0.78-1.4, P = 0.763). The same result was observed on day 40. Bacteriuria occurred more often in older women with increased length of catheterisation.CONCLUSION:Immediate postoperative prophylaxis with PAC does not reduce the risk of postoperative bacteriuria in patients receiving short-term transurethral catheterisation after pelvic surgery.TWEETABLE ABSTRACT:PAC prophylaxis does not reduce the risk of postoperative bacteriuria in patients undergoing pelvic surgery

Live birth rate after female fertility preservation for cancer or haematopoietic stem cell transplantation: a systematic review and meta-analysis of the three main techniques; embryo, oocyte and ovarian tissue cryopreservation

International audienceSTUDY QUESTION What are the chances of achieving a live birth after embryo, oocyte and ovarian tissue cryopreservation (OTC) in female cancer survivors? SUMMARY ANSWER The live birth rates (LBRs) following embryo and oocyte cryopreservation are 41% and 32%, respectively, while for IVF and spontaneous LBR after tissue cryopreservation and transplantation, these rates are 21% and 33%, respectively. WHAT IS KNOWN ALREADY Currently, fertility preservation (FP) has become a major public health issue as diagnostic and therapeutic progress has made it possible to achieve an 80% survival rate in children, adolescents and young adults with cancer. In the latest ESHRE guidelines, only oocyte and embryo cryopreservation are considered as established options for FP. OTC is still considered to be an innovative method, while it is an acceptable FP technique in the American Society for Reproductive Medicine guidelines. However, given the lack of studies on long-term outcomes after FP, it is still unclear which technique offers the best chance to achieve a live birth. STUDY DESIGN, SIZE, DURATION We performed a systematic review and meta-analysis of published controlled studies. Searches were conducted from January 2004 to May 2021 in Medline, Embase and the Cochrane Library using the following search terms: cancer, stem cell transplantation, FP, embryo cryopreservation, oocyte vitrification, OTC and reproductive outcome. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 126 full-text articles were preselected from 1436 references based on the title and abstract and assessed via the Newcastle–Ottawa Quality Assessment Scale. The studies were selected, and their data were extracted by two independent reviewers according to the Cochrane methods. A fixed-effect meta-analysis was performed for outcomes with high heterogeneity. MAIN RESULTS AND THE ROLE OF CHANCE Data from 34 studies were used for this meta-analysis. Regarding cryopreserved embryos, the LBR after IVF was 41% (95% CI: 34–48, I2: 0%, fixed effect). Concerning vitrified oocytes, the LBR was 32% (95% CI: 26–39, I2: 0%, fixed effect). Finally, the LBR after IVF and the spontaneous LBR after ovarian tissue transplantation were 21% (95% CI: 15–26, I2: 0%, fixed-effect) and 33% (95% CI: 25–42, I2: 46.1%, random-effect), respectively. For all outcomes, in the sensitivity analyses, the maximum variation in the estimated percentage was 1%. LIMITATIONS, REASONS FOR CAUTION The heterogeneity of the literature prevents us from comparing these three techniques. This meta-analysis provides limited data which may help clinicians when counselling patients. WIDER IMPLICATIONS OF THE FINDINGS This study highlights the need for long-term follow-up registries to assess return rates, as well as spontaneous pregnancy rates and birth rates after FP. STUDY FUNDING/COMPETING INTEREST(S) This work was sponsored by an unrestricted grant from GEDEON RICHTER France. The authors have no competing interests to declare. REGISTRATION NUMBER CRD42021264042