Extending the clinical spectrum of X-linked Tonne-Kalscheuer syndrome (TOKAS): new insights from the fetal perspective.

INTRODUCTION: Tonne-Kalscheuer syndrome (TOKAS) is a recessive X-linked multiple congenital anomaly disorder caused by RLIM variations. Of the 41 patients reported, only 7 antenatal cases were described. METHOD: After the antenatal diagnosis of TOKAS by exome analysis in a family followed for over 35 years because of multiple congenital anomalies in five male fetuses, a call for collaboration was made, resulting in a cohort of 11 previously unpublished cases. RESULTS: We present a TOKAS antenatal cohort, describing 11 new cases in 6 French families. We report a high frequency of diaphragmatic hernia (9 of 11), differences in sex development (10 of 11) and various visceral malformations. We report some recurrent dysmorphic features, but also pontocerebellar hypoplasia, pre-auricular skin tags and olfactory bulb abnormalities previously unreported in the literature. Although no clear genotype-phenotype correlation has yet emerged, we show that a recurrent p.(Arg611Cys) variant accounts for 66% of fetal TOKAS cases. We also report two new likely pathogenic variants in RLIM, outside of the two previously known mutational hotspots. CONCLUSION: Overall, we present the first fetal cohort of TOKAS, describe the clinical features that made it a recognisable syndrome at fetopathological examination, and extend the phenotypical spectrum and the known genotype of this rare disorder.

The Left Outflow Tract in Fetal Cardiac Screening Examination: Introduction of Quality Criteria Is Not Always Associated With an Improvement of Practice When Supervised by Humans.

OBJECTIVES: Since 2016, the French CNEOF included the left ventricular outflow tract (LVOT) in the second and third trimester of pregnancy in addition to the four-chamber view and the parasagittal view of the right outflow tract. The objective of this study was to define quality criteria for fetal LVOT assessment and to perform a human audit of past and current practices, before and after the implementation of those quality criteria at a large scale. METHODS: Seven quality criteria were investigated and rated from 0 to 1 during three periods of interest. Files were randomly selected from three centers, and average total and specific scores were calculated. RESULTS: LVOT pictures were present in more than 94.3% of reports. The average quality score was 5.49/7 (95% confidence interval [CI]: 5.36-5.62), 5.91/7 (95% CI: 5.80-6.03), and 5.70/7 (95% CI: 5.58-5.82) for the three centers in the three periods of interest. There was no significant difference following the introduction of the quality criteria, 2017 versus 2020, P = .054. CONCLUSION: Fetal LVOT images were present in most of ultrasound reports but the introduction of the proposed quality criteria under human supervision seems not associated with a significant change in practice.

Uncertain fetal head engagement: a prospective randomized controlled trial comparing digital exam with angle of progression.

BACKGROUND: Uncertain fetal head engagement represents 4% of obstetrical situations associated with an increased risk of postpartum hemorrhage, notably in cases of cesarean delivery and increased neonatal impairment owing to failed vaginal instrumental delivery. In this obstetrical condition, cesarean delivery is recommended, but vaginal delivery is possible in two-thirds of the cases. During the second stage of labor, the descent of the fetal head can be assessed by sonography, particularly by measuring the angle of progression. OBJECTIVE: To evaluate, after a prolonged second stage of labor, the impact of measuring the angle of progression in addition to a digital examination on cesarean delivery rates when fetal head engagement remains uncertain. STUDY DESIGN: This open multicenter randomized pragmatic trial included women at term with a singleton cephalic fetus in a clinical occiput anterior position after a prolonged 2-hour second stage of labor with uncertain fetal head engagement. After inclusion in the study, an independent investigator performed ultrasound systematically to confirm the occiput anterior position and measured the angle of progression at the climax of Valsalva pushing. This operator did not participate in labor management. In the study group but not in the control group, the angle of progression was communicated to the obstetrician in charge of labor management. Obstetricians were encouraged to attempt vaginal birth if the angle of progression was >120°. The primary outcome was the cesarean delivery rate. Secondary outcomes were operative delivery rate (cesarean delivery and operative vaginal delivery), maternal complications (third and fourth-degree perineal tears, failed vaginal instrumental delivery, postpartum hemorrhage, hysterectomy), and neonatal outcomes (Apgar score <5 at 10 minutes, umbilical arterial pH <7.10, neonatal wounds, neonatal intensive care unit admission). RESULTS: A total of 45 women were included in the study. Occiput anterior position was confirmed in 33 women: 16 in the study group and 17 in the control group. Women's characteristics at baseline were similar between the groups. The median (range) angles of progression were similar: 138.4° (15) and 140.3° (16.9) in the study and control group, respectively. Cesarean delivery rates were 12.5% in the study group and 41.1% in the control group (P=.06). Secondary outcomes were similar between the 2 groups. No failed vaginal instrumental delivery was reported. CONCLUSION: Measurement of the angle of progression in addition to digital examination when fetal head engagement remained uncertain showed promising results in decreasing cesarean delivery rates. A larger multicenter randomized controlled trial is needed to confirm these results.

Can fetal magnetic resonance imaging aid prognosis in gastroschisis: A multicenter study.

OBJECTIVE: To assess the contribution and impact of fetal magnetic resonance imaging (MRI) in managing fetal gastroschisis. METHODS: We conducted an observational retrospective study of gastroschisis patients at three fetal medicine centers from 2008 to 2019. The primary endpoint was the number of cases in which the MRI provided relevant information related to gastroschisis. RESULTS: A total of 189 patients were included, and our study group included 38 patients who underwent MRI. For the eight patients with suspected gastroschisis, MRI confirmed the diagnosis. In six cases, it provided additional relevant information (spiral turn, intestine ischemia, and bowel size discrepancy). For the 17 patients with ultrasound signs of additional gastrointestinal anomalies, MRI detected one case of unidentified complex gastroschisis on sonography. For the 13 patients undergoing routine MRI, no significant information was obtained. One termination of pregnancy and one fetoscopy were performed a few days after the MRI results. There was no subsequent follow-up or additional bowel complications to support management. CONCLUSION: Although MRI did not change the management of pregnancies complicated by fetal gastroschisis, patients presenting with fetal gastroschisis with intraabdominal bowel dilatation could benefit from MRI to allow for more precise prenatal counseling to predict postnatal intestinal complications before birth.

Early alteration of the locus coeruleus in phenotypic variants of Alzheimer's disease.

Neuropathological studies showed early locus coeruleus (LC) neuronal loss associated with tauopathy in Alzheimer's Disease (AD). We used the LC signal intensity (LC-I) on 3T MRI to assess the LC integrity in AD (n = 37) and controls (n = 17). The LC-I was decreased in AD regardless of typical (amnesic) and atypical presentation (logopenic aphasia/visuo-spatial deficit), from the prodromal stage, and independently of the amyloid load measured by PiB-PET. The LC-I was correlated with memory performance of typical AD. This supports the pathophysiological model in which the LC plays a critical role in AD and may thus be a potential therapeutic target.

Antenatal prognostic factor of fetal echogenic bowel.

OBJECTIVE: The aim of this study was to identify antenatal prognostic factors of neonatal outcomes in cases of fetal echogenic bowel (FEB). STUDY DESIGN: A retrospective study in three tertiary referral centers including fetal echogenic bowel over a 10-year period (from January 2003 to December 2013). The echogenicity of the fetal bowel was graded from 1 to 3, according to Slotnick's definition. Associated echographic findings such as bowel dilations, gallbladder abnormalities, calcifications, extra-abdominal abnormalities, intrauterine growth restriction (IUGR) and a decrease in amniotic fluid volume, if present were also recorded. This was followed by the FEB's sonographic evolution. The sonographic evolution was considered favorable if it was stable or decreasing and unfavorable if the echogenicity of the bowel increased or if additional sonographic findings appeared. Neonates had a pediatric examination in the delivery room and upon discharge from the maternity hospital. An outcome was considered good in the case of on-term delivery of a newborn with normal clinical examination and meconium elimination. RESULTS: Complete pregnancy outcome data were available for 409 pregnancies. 338 newborns had uneventful outcomes (82.6%). Antenatal exploration diagnosed 4 cases of aneuploidy (1 case of trisomy 13, 1 case of trisomy 18 and 2 cases of triploidies), 16 cases of congenital infections, 9 cases of cystic fibrosis and 11 cases of bowel abnormalities. After a multivariate analysis, we discovered the sonographic grade of the echogenic bowel was not a prognostic factor of neonatal outcome. The isolated fetal echogenic bowel had a 6.6-fold increase chance of uneventful outcomes (adjusted odd ratio (aOR) 6.6, 95% CI 3-14.4). Notably, favorable sonographic evolution (aOR 8.1, 95% CI 4.1-16) and late gestational age at the time of the diagnosis (aOR 1.17, 95% CI 1.07-1.27) are independent, good prognostic factors of good neonatal outcomes. None of the 180 fetuses with isolated fetal echogenic bowel and favorable sonographic evolution had adverse outcomes. Among these, 4 cases (0.98%) of aneuploïdy, 17 cases (4.2%) of congenital infections and 9 cases (2.2%) of cystic fibroses were also diagnosed. No cases of Down syndrome (DS) were reported. CONCLUSION: Our study shows that the grade should not be considered a prognostic factor of neonatal outcomes. Our data suggests the need to reevaluate the concept of systematic amniocentesis. Sonographic evolution of fetal bowel is an independent, strong prognostic factor for good neonatal outcomes. It also better defines the FEB prognostic.

Tennis Racket Vibrations and Shock Transmission to the Wrist during Forehand Drive.

This study aimed to investigate the effects of two different racket models and two different forehand drive velocities on the three-dimensional vibration behavior of the racket and shock transmission to the player's wrist under real playing conditions. Nine tennis players performed a series of crosscourt flat forehand drives at two velocities, using a lightly and a highly vibrant racket. Two accelerometers were fixed on the racket frame and the player's wrist. The analysis of vibration signals in both time and frequency domains showed no interaction effect of velocity and racket conditions either on the racket vibration behavior or on shock transmission. An increase in playing velocity enlarged the amount of vibrations at the racket and wrist, but weakly altered their frequency content. As compared to a racket perceived as highly vibrating, a racket perceived as lightly vibrating damped longer in the out-of-plane axis of the racket and shorter on the other axis of the racket and on the wrist, and displayed a lower amount of energy in the high frequency of the vibration signal at the racket and wrist. These findings indicated that the playing velocity must be controlled when investigating the vibration loads due to the racket under real playing conditions. Similarly, a reduced perception of vibration by the tennis player would be linked to decreased amplitude of the racket vibration signal, which may concentrate the signal energy in the low frequencies.

Effects of the racket polar moment of inertia on dominant upper limb joint moments during tennis serve.

This study examined the effect of the polar moment of inertia of a tennis racket on upper limb loading in the serve. Eight amateur competition tennis players performed two sets of 10 serves using two rackets identical in mass, position of center of mass and moments of inertia other than the polar moment of inertia (0.00152 vs 0.00197 kg.m2). An eight-camera motion analysis system collected the 3D trajectories of 16 markers, located on the thorax, upper limbs and racket, from which shoulder, elbow and wrist net joint moments and powers were computed using inverse dynamics. During the cocking phase, increased racket polar moment of inertia was associated with significant increases in the peak shoulder extension and abduction moments, as well the peak elbow extension, valgus and supination moments. During the forward swing phase, peak wrist extension and radial deviation moments significantly increased with polar moment of inertia. During the follow-through phase, the peak shoulder adduction, elbow pronation and wrist external rotation moments displayed a significant inverse relationship with polar moment of inertia. During the forward swing, the magnitudes of negative joint power at the elbow and wrist were significantly larger when players served using the racket with a higher polar moment of inertia. Although a larger polar of inertia allows players to better tolerate off-center impacts, it also appears to place additional loads on the upper extremity when serving and may therefore increase injury risk in tennis players.

Joint Kinetics to Assess the Influence of the Racket on a Tennis Player's Shoulder.

This study aimed at investigating the influence of three rackets on shoulder net joint moments, power and muscle activity during the flat tennis serve under field- conditions. A 6-camera Eagle(®) motion analysis system, operating at 256 Hz, captured racket and dominant upper limb kinematics of the serve in five tennis players under three racket conditions (A: low mass, high balance and polar moment, B: low three moments of inertia, and C: high mass, swingweight and twistweight). The electromyographic activity of six trunk and arm muscles was simultaneously recorded. Shoulder net joint moments and power were computed by 3D inverse dynamics. The results showed that greater shoulder joint power and internal/external rotation peak moments were found to accelerate and decelerate racket A in comparison with the racket C. Moreover, serving with the racket A resulted in less activity in latissimus dorsi muscle during the acceleration phase, and biceps brachii muscle during the follow-through phase when compared with racket C. These initial findings encourage studying the biomechanical measurements to quantify the loads on the body during play in order to reduce them, and then prevent shoulder injuries. Racket specifications may be a critical point for coaches who train players suffering from shoulder pain and chronic upper limb injuries should be considered in relation to the racket specifications of the players. Key PointsLight racket required more joint power than heavy one to achieve similar post impact ball velocity.Serving with a light racket resulted in higher shoulder internal and external rotation moments than using a heavy one for similar performance.Chronic shoulder pain should encourage coaches to check for potentially inappropriate racket specifications of their players.