Screening for small for gestational age using third-trimester ultrasound markers: protocol for a systematic review and meta-analysis of screening test accuracy.

BACKGROUND: Fetal growth restriction (FGR) is a complication of pregnancy associated with major neonatal morbidity and commonly diagnosed at birth based on birth weight below the 5th or the 10th centile. There is no consensus on the use of routine third-trimester ultrasound for the detection of FGR in a general population. This systematic review aims to estimate the performance of third-trimester ultrasound markers in the screening for babies who are small for gestational age in low-risk or general population. METHODS: A systematic review of screening test accuracy will be conducted. The databases MEDLINE, Embase, Cochrane Library, and Web of Science will be searched from their inception until December 2017, as well as reference lists of included studies and previous related review articles. Studies screening for FGR in a low-risk or general population using third-trimester ultrasound markers and reporting low birth weight for gestational age (small for gestational age at birth) as a reference will be eligible. Two reviewers will independently screen references for inclusion, assess the risk of bias, and extract data. The Quality Assessment of Diagnostic Accuracy Study 2 (QUADAS-2) tool will be used to assess the methodological quality and validity of individual studies. The hierarchal summary receiver operating characteristic and random effects hierarchal bivariate models (Bivariate) will be used to estimate the pooled sensitivity and specificity of each ultrasound marker and to compare the discriminative ability of the different ultrasound markers. Subgroup and sensitivity analyses will be performed to explore the heterogeneity between studies and to assess the effect of screening tests' characteristics (e.g., timing) on their discriminative ability. DISCUSSION: This systematic review will determine the relevance of routine third-trimester ultrasound markers in the screening for FGR in low-risk or general population and their usefulness in standard pregnancy care. Additionally, this knowledge synthesis represents a step in the optimization of the discriminative ability of third-trimester ultrasound and predictive tools, allowing for targeted interventions aiming at the reduction of FGR complications and ultimately improving infants' health. SYSTEMATIC REVIEW REGISTRATION: This protocol has been registered at PROSPERO: international prospective register of systematic reviews. The register number is CRD42018085564 .

Ultrasonographic Evaluation of Uterine Scar Niche before and after Laparoscopic Surgical Repair: A Case Report.

Context Uterine scar defects or scar niche are relatively common after cesarean delivery. An association has been observed between the severity of scar defect, also known as isthmocele, some gynecologic symptoms, and the risk of uterine scar dehiscence at the next delivery. It has been suggested that surgical repair of scar defect could improve the gynecological symptoms, but it remains unclear whether such surgery mends the uterine scar itself. Case Report We report the case of a woman with uterine scar defect in whom laparoscopic repair significantly improved the gynecological symptoms without affecting the uterine scar, evaluated by hysterosonography. Conclusion This case highlights the significant dearth of knowledge surrounding the diagnosis, consequences, and benefits of surgical repair of uterine scar defect after cesarean.

Impact of single- vs double-layer closure on adverse outcomes and uterine scar defect: a systematic review and metaanalysis.

A systematic review and metaanalysis were performed through electronic database searches to estimate the effect of uterine closure at cesarean on the risk of adverse maternal outcome and on uterine scar evaluated by ultrasound. Randomized controlled trials, which compared single vs double layers and locking vs unlocking sutures for uterine closure of low transverse cesarean, were included. Outcomes were short-term complications (endometritis, wound infection, maternal infectious morbidity, blood transfusion, duration of surgical procedure, length of hospital stay, mean blood loss), uterine rupture or dehiscence at next pregnancy, and uterine scar evaluation by ultrasound. Twenty of 1278 citations were included in the analysis. We found that all types of closure were comparable for short-term maternal outcomes, except for single-layer closure, which had shorter operative time (-6.1 minutes; 95% confidence interval [CI], -8.7 to -3.4; P < .001) than double-layer closure. Single layer (-2.6 mm; 95% CI, -3.1 to -2.1; P < .001) and locked first layer (mean difference, -2.5 mm; 95% CI, -3.2 to -1.8; P < .001) were associated with lower residual myometrial thickness. Two studies reported no significant difference between single- vs double-layer closure for uterine dehiscence (relative risk, 1.86; 95% CI, 0.44-7.90; P = .40) or uterine rupture (no case). In conclusion, current evidence based on randomized trials does not support a specific type of uterine closure for optimal maternal outcomes and is insufficient to conclude about the risk of uterine rupture. Single-layer closure and locked first layer are possibly coupled with thinner residual myometrium thickness.

TNF-α-mediated caspase-8 activation induces ROS production and TRPM2 activation in adult ventricular myocytes.

AIMS: TRPM2 is a Ca(2+)-permeable cationic channel of the transient receptor potential (TRP) superfamily that is linked to apoptotic signalling. Its involvement in cardiac pathophysiology is unknown. The aim of this study was to determine whether the pro-apoptotic cytokine tumour necrosis factor-α (TNF-α) induces a TRPM2-like current in murine ventricular cardiomyocytes. METHODS AND RESULTS: Adult isolated cardiomyocytes from C57BL/6 mice were exposed to TNF-α (10 ng/mL). Western blotting showed TRPM2 expression, which was not changed after TNF-α incubation. Using patch clamp in whole-cell configuration, a non-specific cation current was recorded after exposure to TNF-α (ITNF), which reached maximal steady-state amplitude after 3 h incubation. ITNF was inhibited by the caspase-8 inhibitor z-IETD-fmk, the antioxidant N-acetylcysteine, and the TRPM2 inhibitors clotrimazole, N-(P-amylcinnamoyl) anthranilic acid and flufenamic acid (FFA). TRPM2 has previously been shown to be activated by ADP-ribose, which is produced by poly(ADP-ribose) polymerase 1 (PARP-1). TNF-α exposure resulted in increased poly-ADP-ribosylation of proteins and the PARP-1 inhibitor 3-aminobenzamide inhibited ITNF. TNF-α exposure increased the mitochondrial production of reactive oxygen species (ROS; measured with the fluorescent indicator MitoSOX Red), and this increase was blocked by the caspase-8 inhibitor z-IETD-fmk. Clotrimazole and TRPM2 inhibitory antibody decreased TNF-α-induced cardiomyocyte death. CONCLUSION: These results demonstrate that TNF-α induces a TRPM2 current in adult ventricular cardiomyocytes. TNF-α induces caspase-8 activation leading to ROS production, PARP-1 activation, and ADP-ribose production. TNF-induced TRPM2 activation may contribute to cardiomyocyte cell death.

Survey on uterine closure and other techniques for Caesarean section among Quebec's obstetrician-gynaecologists.

OBJECTIVE: To evaluate the preferred types of uterine closure at Caesarean section among Quebec's obstetrician-gynaecologists. METHODS: An anonymous survey with multiple-choice and open questions was sent by email to all members of the Association des Obstétriciens-Gynécologues du Québec in clinical practice. The primary response of interest was the type of uterine closure that would be favoured for a primigravida undergoing an elective CS at term for a breech fetus. Secondary responses of interest included type of uterine closure for CS performed for other indications, and methods of closure for the bladder flap, parietal peritoneum, rectus abdominis muscle, subcutaneous tissue, and skin. Results were stratified according to the number of years in practice. RESULTS: Of 454 persons targeted, 176 (39%) responded. Responders were more likely to have fewer years in practice than the targeted population in general. The closures for a primigravida undergoing an elective CS at term for a breech presentation were, in order of preference: (1) a double-layer closure combining a first locked layer and an imbricating second layer (61%), (2) a double-layer closure combining a first unlocked layer and an imbricating second layer (28%), (3) a locked single layer (5%), (4) an unlocked single layer (5%), and (5) other techniques (1%). A locked single-layer closure was more frequently used for repeat CS (29%), and it was the favoured technique (40%) when tubal ligation was performed at the time of CS (P < 0.05). CONCLUSION: Double-layer closure is the type of uterine closure most preferred by obstetricians in Quebec. However, the first layer is locked by two thirds of obstetricians and unlocked by the remainder.

Objectif : Évaluer les types privilégiés de fermeture utérine au moment de la césarienne chez les obstétriciens-gynécologues du Québec. Méthodes : Un sondage anonyme comptant des questions ouvertes et à choix multiples a été transmis par courriel à tous les membres de l'Association des obstétriciens-gynécologues du Québec en pratique clinique. La question qui nous intéressait principalement concernait le type de fermeture utérine qui serait privilégié dans le cas d'une primigravide subissant une césarienne planifiée à terme en raison d'un fœtus en présentation du siège. Parmi les questions suscitant un intérêt secondaire de notre part, on trouvait celles qui s'intéressaient au type de fermeture utérine pour ce qui est des césariennes menées en raison d'autres indications et celles qui traitaient des méthodes de fermeture de la jonction avec la vessie, du péritoine pariétal, du muscle grand droit de l'abdomen, du tissu sous-cutané et de la peau. Les résultats ont été stratifiés en fonction du nombre d'années de pratique. Résultats : Parmi les 454 personnes ciblées, 176 (39 %) ont rempli le sondage. Les répondants étaient plus susceptibles de compter moins d'années de pratique que la population ciblée en général. Les types de fermeture utérine privilégiés dans le cas d'une primigravide subissant une césarienne planifiée à terme en raison d'un fœtus en présentation du siège ont été, en ordre de préférence : (1) une fermeture en deux plans combinant un premier plan fermé au moyen d'un surjet passé et un deuxième plan imbriqué (61 %), (2) une fermeture en deux plans combinant un premier plan fermé au moyen d'un surjet non passé et un deuxième plan imbriqué (28 %), (3) une fermeture en un plan au moyen d'un surjet passé (5 %), (4) une fermeture en un plan au moyen d'un surjet non passé (5 %), et (5) d'autres techniques (1%). La fermeture en un plan au moyen d'un surjet passé a été utilisée plus fréquemment dans les cas de césarienne itérative (29 %) et a constitué la technique privilégiée (40 %) lorsqu'une ligature des trompes était menée au moment de la césarienne (P < 0,05). Conclusion : La fermeture en deux plans constitue le type de fermeture utérine le plus privilégié par les obstétriciens du Québec. Cependant, deux tiers des obstétriciens font appel à un surjet passé pour le premier plan, tandis que les autres font appel à un surjet non passé.

[Development of technicality indices of hysterectomies in Quebec]. / Évolution de l'indice de technicité des hystérectomies au Québec

OBJECTIVE: Assess the evolution of the technicity index for hysterectomies in Québec. METHODS: We used the ADAM ( Analyse en direct des actes médicaux) database to determine the number of hysterectomies done each year within 79 hospitals in Québec from 2002 to 2009. Excluding oncologically indicated surgeries, we calculated the number of hysteretomies and the proportion performed by the vaginal route (laparoscopically assisted or not), by laparoscopu, and by laparotomy for each study year. RESULTS: We obtained complete data fo 67 (85%) of 79 hospitals, for a total of 74 210 (94%) of 79 305 hysterectomies done. We observed a decline in the total number of hysterestomies from 12 860 in 2002-2003 to 8010 in 2008-2009 (P<0.001) Furthermore, the proportion of hysterectomies done by laparoscopy increased, the proportion of vaginal hysterectomies remained stable, and the proportion of hysterectomies done by laparoscopy increased. For all of Québec, the technicity index increased from 39.9% in 2002-2003 to 44.3% in 2008-2009 (P<0.001). CONCLUSION: The number of hysterectomies is declining and the technicity index is increasing in Quebec. We believe that this can be attributed to an increased use of medical alternatives and the presence of gynaecologists better trained in advanced laparoscopic surgery.

Ryanodine receptor leak mediated by caspase-8 activation leads to left ventricular injury after myocardial ischemia-reperfusion.

Myocardial ischemic disease is the major cause of death worldwide. After myocardial infarction, reperfusion of infracted heart has been an important objective of strategies to improve outcomes. However, cardiac ischemia/reperfusion (I/R) is characterized by inflammation, arrhythmias, cardiomyocyte damage, and, at the cellular level, disturbance in Ca(2+) and redox homeostasis. In this study, we sought to determine how acute inflammatory response contributes to reperfusion injury and Ca(2+) homeostasis disturbance after acute ischemia. Using a rat model of I/R, we show that circulating levels of TNF-α and cardiac caspase-8 activity were increased within 6 h of reperfusion, leading to myocardial nitric oxide and mitochondrial ROS production. At 1 and 15 d after reperfusion, caspase-8 activation resulted in S-nitrosylation of the RyR2 and depletion of calstabin2 from the RyR2 complex, resulting in diastolic sarcoplasmic reticulum (SR) Ca(2+) leak. Pharmacological inhibition of caspase-8 before reperfusion with Q-LETD-OPh or prevention of calstabin2 depletion from the RyR2 complex with the Ca(2+) channel stabilizer S107 ("rycal") inhibited the SR Ca(2+) leak, reduced ventricular arrhythmias, infarct size, and left ventricular remodeling after 15 d of reperfusion. TNF-α-induced caspase-8 activation leads to leaky RyR2 channels that contribute to myocardial remodeling after I/R. Thus, early prevention of SR Ca(2+) leak trough normalization of RyR2 function is cardioprotective.

The role of uterine closure in the risk of uterine rupture.

OBJECTIVE: To evaluate the effects of prior single-layer compared with double-layer closure on the risk of uterine rupture. METHODS: A multicenter, case-control study was performed on women with a single, prior, low-transverse cesarean who experienced complete uterine rupture during a trial of labor. For each case, three women who underwent a trial of labor without uterine rupture after a prior low-transverse cesarean delivery were selected as control participants. Risk factors such as prior uterine closure, suture material, diabetes, prior vaginal delivery, labor induction, cervical ripening, birth weight, prostaglandin use, maternal age, gestational age, and interdelivery interval were compared between groups. Conditional logistic regression analyses were conducted. RESULTS: Ninety-six cases of uterine rupture, including 28 with adverse neonatal outcome, and 288 control participants were assessed. The rate of single-layer closure was 36% (35 of 96) in the case group and 20% (58 of 288) in the control group (P<.01). In multivariable analysis, single-layer closure (odds ratio [OR] 2.69; 95% confidence interval [CI] 1.37-5.28) and birth weight greater than 3,500 g (OR 2.03; 95% CI 1.21-3.38) were linked with increased rates of uterine rupture, whereas prior vaginal birth was a protective factor (OR 0.47; 95% CI 0.24-0.93). Single-layer closure was also related to uterine rupture associated with adverse neonatal outcome (OR 2.89; 95% CI 1.01-8.27). CONCLUSION: Prior single-layer closure carries more than twice the risk of uterine rupture compared with double-layer closure. Single-layer closure should be avoided in women who could contemplate future vaginal birth after cesarean delivery. LEVEL OF EVIDENCE: II.