[Prenatal ultrasound prognostic of myelomeningocele at the era of fetal surgery]. / Évaluation pronostique prénatale échographique de la myéloméningocèle à l'ère de la chirurgie fœtale.

Myelomeningocele (MMC) is a severe congenital condition responsible for motor and sensory impairments of the lower limbs, incontinence and cognitive impairment. Its screening, sometimes as early as the first trimester, is one of the major goals of modern prenatal care, supported by the emergence of prenatal surgery that results in a significant improvement in motor function, ambulation and ventriculoperitoneal shunt rate in patients undergoing in-utero surgery. From screening to pre- and post-operative prognostic evaluation, prenatal ultrasound is now an essential tool in the antenatal management of this condition. Using the multi planar and three-dimensional modes, it can be used to assess the vertebral level of MMC, which remains the key antenatal prognostic marker for motor function and ambulation, incontinence and the need for a ventriculo-peritoneal shunt. A careful and systematic ultrasound examination also makes it possible to assess the severity and progression of ventriculomegaly, to search for associated cerebral, spinal cord or vertebral anomalies, or to rule out exclusion criteria for in-utero surgery such as severe kyphosis or serious cortical anomalies. New tools from post-natal evaluation, such as the "metameric" ultrasound assessment of lower limb mobility, appear to be promising either for the initial examination or after in-utero surgery. Ultrasonography, associated with fetal MRI, cytogenetic and next generation sequencing, now allows a highly customized prognostic evaluation of these fetuses affected by MMC and provides the parents with the best possible information on the expected benefits and limitations of fetal surgery.

Accuracy of qualitative and quantitative cranial ultrasonographic markers in first-trimester screening for open spina bifida and other posterior brain defects: a systematic review and meta-analysis.

BACKGROUND: The significant number of qualitative and quantitative ultrasound markers described for first-trimester screening of open spina bifida (OSB) and other posterior brain defects (oPBD) has resulted in their complex implementation and interpretation for a widespread screening and in a lack of consensus regarding diagnostic accuracy. OBJECTIVES: To assess and compare the accuracy of qualitative and quantitative cranial sonographic markers at 11-14 weeks of gestation for the detection of OSB and oPBD. SEARCH STRATEGY: A systematic literature search was performed in MEDLINE and COCHRANE from 2009 to April 2020. SELECTION CRITERIA: Studies assessing the diagnostic accuracy of quantitative and/or qualitative ultrasound signs to predict OSB and oPBD were included. Cohort studies and case-control studies were also considered. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed the risk of bias. The overall pooled estimate and a summary receiver operating characteristic curve was estimated for each subgroup (qualitative and quantitative assessment). MAIN RESULTS: Twenty-three studies were included in our meta-analysis. The pooled sensitivity and specificity for qualitative assessment were 76.5% and 99.6%, and for quantitative assessment were 84.5% and 96.3%, respectively; specificity for the qualitative ultrasound signs was significantly higher (P = 0.001). The overall sensitivity of cranial sonographic markers for the screening of oPBD was 76.7% and specificity was 97.5%. CONCLUSIONS: The qualitative approach demonstrated greater specificity, so this would appear to be more appropriate for daily screening, as a first-line tool, whereas the quantitative approach should be reserved for expert ultrasound. TWEETABLE ABSTRACT: This study highlights the relevance of first-trimester qualitative ultrasound signs in the screening of open spina bifida.

[How to deal with a fetal head circumference lower than the third percentile?] / Gestion prénatale des fœtus avec un périmètre crânien inférieur au 3e percentile.

The prenatal finding of a head circumference (HC) below the 3rd percentile (p) remains, in the same way as short femur or increased nuchal translucency with normal karyotype, one the most difficult situations for the praticionner in the setting of prenatal diagnosis. Microcephaly is a gateway to possible cerebral pathologies, but the main objective is to identify serious prenatal situations. A standardized HC measurement, the use of adapted reference tools and charts, longitudinal following of cephalic biometrics in high-risk situations, and systematic central nervous system analysis can increase the diagnostic performance of ultrasound which is often disappointing for microcephaly. The early distinction between associated or isolated microcephaly makes it possible to quickly orient the prenatal management and counseling. Fetal MRI and genetic counseling are fundamental in this context, making it possible to specify at best the etiological diagnosis and to provide assistance to the neuropediatrician in the establishment of an often uncertain prognosis. The recent increase in cases of microcephaly concomitant with the epidemic of the ZIKA virus is an additional argument to improve our practices and the daily apprehension of HC<3rd p.

[Analysis of fetal posterior fossa during the first trimester ultrasound scan]. / Analyse de la fosse postérieure fœtale lors de l'échographie du premier trimestre de la grossesse.

The diagnosis of an abnormal fetal posterior fossa is usually done during the second trimester scan. However, some forms of open spina bifida with Arnold-Chiari malformation can be detected from the first trimester ultrasound with a precise examination of the posterior fossa and intracranial translucency. Furthermore, other abnormalities of the posterior fossa such as cystic malformations also seem to be accessible to early detection. This work detailed the possible usual and unusual aspects of the posterior fossa individualized during the first trimester ultrasound scan. Identifying an unusual appearance may identify high-risk fetus to present an abnormality of the posterior fossa. Then, thorough analysis of the fetal brain from 18 weeks will often differentiate a normal variant of a real brain malformation.

[Surgical treatment of postpartum hemorrhage]. / Prise en charge chirurgicale d'une hémorragie du post-partum.

OBJECTIVE: Systematic revue of different conservative and non-conservative surgical treatment of postpartum hemorrhage (PPH). Elaboration of surgical strategy after failed medical treatment of PPH. METHODS: French and English publications were identified through PubMed and Cochrane databases. RESULTS: Each obstetrical unit has to rewrite a full protocol of management of PPH depending on local environment quickly available in theatre (professional consensus). Conservative surgical treatment of PPH: efficacy of vascular ligature (bilateral uterine artery ligation (BUAL) or bilateral hypogastric artery ligation (BHAL)) as a first line of surgical treatment of PPH is about 60 % to 70 % (EL4). Bilateral uterine artery ligation (BUAL) is easy to perform with low rate of immediate severe complication (professional consensus). BUAL as BHAL seems not to affected fertility and obstetrical outcomes of next pregnancies (EL4). Efficacy of haemostatics brace suturing in case of failed medical treatment of PPH is about 75 % (EL3), without risk of major obstetrical complications at the next pregnancy (EL4). Radical surgical treatment of PPH: total hysterectomy is not significantly associated with more urinary tract injury in comparison with subtotal hysterectomy (EL3). Choice of surgical procedure of hysterectomy (total or subtotal) will depend on local consideration and clinicians habits (professional consensus). Surgical strategy: conservative surgical treatment are efficient and associated with low morbidity, they have to be primarily performed in women with further fertility desire. Specific medical consideration as massive PPH or cardiovascular instability has to consider performing haemostatic hysterectomy as the first line surgical treatment of PPH. PPH during caesarean delivery: in case of PPH during caesarean section, embolisation is not recommended, surgical treatment using vascular devascularisation or compression brace suturing should be performed (professional consensus). Surgical conservative technique will depend on local considerations and clinicians habits (professional consensus). PPH diagnosed after caesarean section should indicate relaparotomy. Arterial embolisation, if quickly vacant in the same hospital, may be performed in case of cardiovascular stability without surgical complication diagnoses on intraperitoneal hemorrhage (professional consensus). PPH during vaginal delivery: cardiovascular instability centre indicate the interhospital transfer and must lead to achieve haemostatic surgery on site (professional consensus). In the presence of a unit of embolisation in the maternity delivery, it is preferable to move towards embolisation, if maternal hemodynamic status permits (professional consensus). In case of cardiovascular stability associated with absence of heavy bleeding, the interhospital transfer may be considered for arterial embolisation (professional consensus). CONCLUSION: When medical treatment of PPH failed, conservative surgical treatment has a 70 % efficacy to stop hemorrhage whatever treatment used (vascular ligature or haemostatics brace suturing). In absence of rapid response to conservative medical and surgical treatment, hysterectomy should be performed without delay (professional consensus).

Assembling the building blocks: structure and function of inhibitor of apoptosis proteins.

Control of apoptotic signalling pathways depends on the balance between proapoptotic and prosurvival molecules. The 'inhibitor of apoptosis' (IAP) proteins are negative regulators of apoptosis that function by inhibiting the executioners of cell death (caspases), or by blocking the pathways that activate them. The IAP proteins function as ubiquitin E3 ligases and possess protein-protein interaction domains. IAPs can promote the addition of ubiquitin to themselves and to the substrate proteins that they interact with either directly or indirectly through adaptor proteins. The balance between substrate and autoubiquitylation seems to be important for their activity. In this review, we describe the structural features of IAP proteins as they are currently understood, and discuss how each domain contributes to IAP function. It is clear that to advance our understanding of these complex proteins, we must decipher how the domains operate in concert and how each domain impacts on the activity of the other.

Structure of the MDM2/MDMX RING domain heterodimer reveals dimerization is required for their ubiquitylation in trans.

MDM2, a ubiquitin E3-ligase of the RING family, has a key role in regulating p53 abundance. During normal non-stress conditions p53 is targeted for degradation by MDM2. MDM2 can also target itself and MDMX for degradation. MDMX is closely related to MDM2 but the RING domain of MDMX does not possess intrinsic E3-ligase activity. Instead, MDMX regulates p53 abundance by modulating the levels and activity of MDM2. Dimerization, mediated by the conserved C-terminal RING domains of both MDM2 and MDMX, is critical to this activity. Here we report the crystal structure of the MDM2/MDMX RING domain heterodimer and map residues required for functional interaction with the E2 (UbcH5b). In both MDM2 and MDMX residues C-terminal to the RING domain have a key role in dimer formation. In addition we show that these residues are part of an extended surface that is essential for ubiquitylation in trans. This study provides a molecular basis for understanding how heterodimer formation leads to stabilization of MDM2, yet degradation of p53, and suggests novel targets for therapeutic intervention.

[Malignant transformation of abdominal wall endometriosis: a new case report]. / Transformation maligne d'une endométriose pariétale.

Cancer arising in abdominal wall endometriosis is a rare event, hindering diagnosis and making management uncertain. A cesarean section scar is generally at the origin of the disease. We report the case of a 45-year-old woman, with a past medical history of cesarean deliveries, complaining of a repeat abdominal wall endometriosis which transformed into a clear-cell carcinoma. Outcome was rapidly fatal. Compared with endometriosis-associated ovarian carcinoma, the prognosis of this abdominal scar complication is poor. In the literature, survival rate reaches only 57% after a short follow-up of 20 months. Clear-cell carcinoma is the most common histological subtype, followed by endometrioid carcinoma. Radical surgery is the main treatment. Good technique and proper care during cesarean section may help in preventing this endometriosis complication.

Skills retention for insertion of the Combitube and laryngeal mask airway.

OBJECTIVE: To determine if the skills to successfully ventilate using the laryngeal mask (The Laryngeal Mask Company Limited, Henley on Thames, United Kingdom) and Combitube (The Kendall Company, Mansfield, USA) can be retained after seven months. METHODS: Nursing, medical and theatre staff from Dunedin Hospital were recruited in a prospective study. Subjects were taught to insert and ventilate an Ambuman manikin using both devices. Subjects were tested on their ability to ventilate the manikin with both devices within one month then following a six-month period. RESULTS: A total of 101 subjects were recruited with 86 subjects retested at least six months later. Initial testing resulted in subjects successfully ventilating the manikin in 90% (laryngeal mask) and 92% (Combitube) of attempts. At retesting, successful ventilation was achieved in 85% (laryngeal mask) and 77% (Combitube) of attempts. The decline in skills level was significant for the Combitube only (95% CI 4% to 26%). CONCLUSION: The ability to successfully ventilate is better maintained with the laryngeal mask than the Combitube after seven months.

Methyl methacrylate levels in unwashed salvage blood following unilateral total knee arthroplasty.

To evaluate the safety of autologous reinfusion of drain blood in total knee arthroplasty (TKA), eight patients were prospectively evaluated to quantify levels of methyl methacrylate (MMA) monomer in systemic blood, and in their drain blood after unilateral cemented TKA. The systemic blood was analyzed before and after reinfusion of the drain blood. The drain blood was analyzed before reinfusion, and both before and after filtration through a 40-microm filter. A separate study was performed on 10 patients to assess the effect of blood, time, and filtration on MMA levels. Levels of MMA monomer in salvage blood were low enough to allow safe reinfusion. Systemic blood showed no evidence of MMA monomer either before reinfusion of salvage blood or at 5 minutes after reinfusion. Elimination of MMA is dependent on the time that MMA is exposed to blood and is independent of filtration.

Family planning decisions after prenatal detection of fetal abnormalities.

OBJECTIVE: Our purpose was to assess the family planning decisions made by women found to be carrying fetuses with chromosome abnormalities or neural tube defects. STUDY DESIGN: We studied the family planning decisions of 132 women carrying fetuses with chromosome abnormalities (n = 91) or neural tube defects (n = 41) with regard to prenatal diagnosis, pregnancy management decision, patient's gravidity, and maternal and gestational age. RESULTS: Twenty women (17 carrying fetuses with chromosome abnormalities and 3 with fetal neural tube defects) elected permanent sterilization after completion of the affected pregnancy. Only maternal age and fetal chromosome abnormalities were associated with a decision to obtain permanent sterilization. CONCLUSIONS: Most women carrying fetuses with chromosome abnormalities or neural tube defects will not choose permanent sterilization after completion of the pregnancy. Delaying such decisions until resolution of grief and depression is now facilitated by the availability of safe, reliable, and relatively long-term reversible contraceptive agents.

PIP: Clinicians examined the family planning decisions of 3938 women who underwent prenatal diagnosis (ultrasonography, amniocentesis, or chorionic villus sampling) at the Division of Reproductive Genetics at the University of Tennessee in Memphis between January 1988 and May 1993. 104 women were carrying fetuses with chromosome abnormalities, of whom 92 opted to terminate their pregnancies. 57 women were carrying fetuses with neural tube defects, of whom 49 chose to end their pregnancies. Among the 91 fetal chromosome abnormality cases with complete information on family planning decisions, 84 had autosomal abnormalities and 7 had sex chromosome abnormalities. Among the 41 fetal neural tube defect cases with complete information on family planning decisions, 22 had spina bifida and 19 had anencephaly. The mean age of women with a chromosome abnormality fetus was higher than that of those with a neural tube defect fetus (36.8 vs. 27.3 years; p 0.03). Just 20 women (15.2%) chose permanent sterilization after continuing or terminating the affected pregnancy. Women carrying fetuses with chromosome abnormalities were more likely to choose permanent sterilization than those carrying fetuses with neural tube defects (18.7% vs. 7.3%; p 0.03). Advanced maternal age was associated with the decision to undergo permanent sterilization (p 0.04). Physicians should counsel women who have opted to terminate a pregnancy of an abnormal fetus to delay any decision to undergo permanent sterilization to allow for resolution of grief and depression. They should advise the women to use safe, reliable, and long term reversible contraceptive agents (e.g., Norplant subdermal implant system, the injectable Depo-Provera, IUDs, and oral contraceptives).

Significance of septations in isolated fetal cystic hygroma detected in the first trimester.

Recent reports have indicated an increased risk for fetal chromosome abnormalities, especially autosomal trisomy, in fetuses with isolated cystic hygroma, or prominent nuchal membranes, detected by ultrasonography during the first trimester. However, these reports present contradictory information regarding the prognostic significance of septations within the cystic hygroma. We evaluated, in blind fashion, 55 consecutive cases of isolated fetal cystic hygroma detected at or before 13.9 weeks' gestation to determine the association between septations and fetal chromosome complement. Septations were associated (P < 0.05) with an increased risk for fetal chromosome abnormalities. However, the incidence of chromosome abnormalities was also increased (12.5 per cent) among cases not characterized by septations. Thus, we believe it prudent to offer invasive prenatal testing to all women found to be carrying fetuses with cystic hygroma, irrespective of the presence or absence of septations.

Prilocaine leakage during tourniquet inflation in intravenous regional anaesthesia: the influence of fracture manipulation.

Recent evidence has shown that there may be leakage of anaesthetic drugs into the systemic circulation during the tourniquet inflation phase of intravenous regional anaesthesia. This, together with increased pressure in forearm vessels during manipulation of fractures, prompted the measurement of arterial levels of local anaesthetic to assess potential toxicity. Prilocaine levels were measured in nine patients undergoing manipulation of Colles' fractures and six patients undergoing other upper limb procedures. Eleven patients had measurable concentrations of prilocaine in the arterial circulation during the time the tourniquet was inflated, the maximum levels being measured in those patients having fractures manipulated. Considerable vigilance should be ensured during the time of tourniquet inflation in intravenous regional anaesthesia, particularly for fracture manipulation.