National registry of thoracoamniotic shunting using a double-basket catheter: A post-marketing surveillance registry of 295 patients with fetal hydrothorax.

OBJECTIVE: We report on the 1-year outcomes of fetuses who underwent thoracoamniotic shunting (TAS) with a double-basket catheter for fetal hydrothorax (FHT) using a national post-marketing surveillance registry. METHODS: This surveillance study was conducted for cases enrolled between 2011 and 2019. Preoperative, operative, and postoperative findings and outcomes had to be reported through the national surveillance website. RESULTS: Forty-three institutes enrolled 295 patients. In 60 patients, associated abnormalities were diagnosed after birth. Among the 235 patients with isolated hydrothorax, the survival rate at 1 year of age was 70.5%. Among these patients, 89% did not require oxygen or other respiratory support. The 1-year survival rate in complicated cases was 27%. Trisomy 21 was the most common associated problem (40%). Catheter associated problems, including dislocation (25%), obstruction (24%), and preterm rupture of the membranes (6%) were observed, but there were no severe maternal complications. TAS before 29.5 weeks of gestation (odds ratio [OR] 0.16) and skin edema and ascites (OR 0.06) were risk factors for death at one year, whereas appropriate shunt location for >28 days (OR 4.2) was a protective factor. CONCLUSION: We report a favorable survival rate in fetuses with isolated FHT treated with this double-basket catheter.

Reelin regulates the migration of late-born hippocampal CA1 neurons via cofilin phosphorylation.

Reelin, a large secreted glycoprotein, plays an important role in neuronal migration during brain development. The C-terminal region (CTR) of Reelin is involved in the efficient activation of downstream signaling and its loss leads to abnormal hippocampal layer formation. However, the molecular mechanism by which Reelin CTR regulates hippocampal development remains unknown. Here, we showed that the migration of late-born, but not early-born, neurons is impaired in the knock-in mice in which Reelin CTR is deleted (ΔC-KI mice). The phosphorylation of cofilin, an actin-depolymerizing protein, was remarkably decreased in the hippocampus of the ΔC-KI mice. Exogenous expression of pseudo-phosphorylated cofilin rescued the ectopic positioning of neurons in the hippocampus of ΔC-KI mice. These results suggest that Reelin CTR is required for the migration of late-born neurons in the hippocampus and that this event involves appropriate phosphorylation of cofilin.

Anterior Malreduction is Associated With Lag Screw Cutout After Internal Fixation of Intertrochanteric Fractures.

BACKGROUND: Lag screw cutout is a devastating complication after internal fixation of an intertrochanteric fracture. Although the tip-apex distance (TAD) is known to be associated with this complication, another factor we thought was potentially important-fracture reduction on an oblique lateral view-has not, to our knowledge, been explored. QUESTIONS/PURPOSES: (1) Is a well-reduced fracture position on an oblique lateral view after internal fixation of intertrochanteric fracture associated with a lower odds of postoperative cutout, independently of the TAD? (2) Is postoperative sliding of the lag screw after fixation associated with postoperative cutout? METHODS: Patients with intertrochanteric fractures who were at least 65 years old and who had been treated with internal fixation in one of six facilities between July 2011 and December 2017 were included. All patients in the study group had lag screw cutout, and controls were selected by risk-set sampling of age-matched and sex-matched patients using a ratio of 4:1 for patients from each hospital. Of the 2327 intertrochanteric fractures, there were 36 patients (0.02 per person-year), with a mean age of 85 years; 89% (32) were women. In the control group, there were 135 controls. There was no difference in age or sex between the two groups. Sagittal reduction was evaluated using an immediate postoperative oblique lateral radiograph (anterior malreduction versus anatomic reduction or posterior malreduction). The association between anterior malreduction and the odds of cutout was estimated by conditional logistic regression analysis with the TAD and interaction between the TAD and the reduced position as covariates. As a sensitivity analysis, we estimated whether sliding within 2 weeks postoperatively was associated with cutout. RESULTS: After controlling for the potentially confounding variables of age and sex, we found that anterior malreduction was independently associated with a higher odds of cutout compared with anatomic reduction or posterior malreduction (adjusted OR 4.2 [95% CI 1.5 to 12]; p = 0.006). There was also an independent association between cutout and larger TAD (≥ 20 mm) (adjusted OR 4.4 [95% CI 1.4 to 14]; p = 0.01). However, the association between cutout and reduction was not modified by the TAD (adjusted OR of interaction term 0.6 [95% CI 0.08 to 4]; p = 0.54). Postoperative sliding ≥ 6 mm within 2 weeks was associated with higher odds of cutout after adjusting for age and sex (adjusted OR 11 [95% CI 3 to 40]; p < 0.001). CONCLUSION: In patients older than 65 years with intertrochanteric fractures, anterior malreduction on a lateral oblique view was associated with much greater odds of postoperative cutout than anatomic reduction or posterior malreduction. Because anterior malreduction is within the surgeon's control, our findings may help surgeons focus on intraoperative reduction on an oblique lateral view to prevent cutouts. Although this factor is a reliable indicator, the results should be applied to cephalomedullary nails, because there was only one patient with cutout among those with sliding hip screws. Because this study was conducted in a homogenous Japanese population, future studies should focus on the association between anterior malreduction and cutout in people of different ethnicities, adjusting for confounding factors such as implant type and surgeon level. LEVEL OF EVIDENCE: Level III, therapeutic study.

Neonatal respiratory complications in twins at 36-38 weeks of gestation.

BACKGROUND: Twin pregnancies are associated with a high risk of perinatal mortality and morbidity. Late preterm or early term delivery is frequently performed to avoid unexpected fetal death in uncomplicated twin pregnancies. Nonetheless, delivery before full term is associated with neonatal respiratory complications. This study aimed to evaluate perinatal respiratory complications in twins delivered between 36 and 38 weeks of gestation. METHODS: A retrospective cohort study was conducted on twins delivered between 36 and 38 weeks of gestation from January 2008 to June 2020. The primary outcomes were the incidence of composite neonatal respiratory morbidity, which included respiratory distress syndrome, transient tachypnea of the newborn, meconium aspiration syndrome, mechanical ventilation or continuous positive airway pressure according to gestational age at delivery, and chorionicity. The relationship between gestational age at delivery and composite neonatal respiratory morbidity was evaluated using multivariate logistic regression analysis adjusted for potential confounders. RESULTS: This study included 1608 twins (614 monochorionic diamniotic twins, 994 dichorionic diamniotic twins). At 36, 37, and 38 weeks of gestation, the frequencies of composite neonatal respiratory morbidity were 19.4%, 10.7%, and 9.2% in dichorionic diamniotic twins and 13.6%, 8.7%, and 9.4% in monochorionic diamniotic twins, respectively. In dichorionic diamniotic twins, the composite neonatal respiratory morbidity rate was higher for twins delivered at 36 weeks of gestation than for those delivered at 37 weeks. No significant differences between monochorionic diamniotic twins were detected. CONCLUSIONS: In uncomplicated dichorionic diamniotic twin pregnancies, delivery should be considered after 37 weeks of gestation to reduce neonatal respiratory complications.

Effect of postoperative fracture gap on bone union: A retrospective cohort analysis of simple femoral shaft fractures.

BACKGROUND: Intramedullary nailing (IMN) is considered the gold-standard treatment for femoral shaft fractures. The post operative fracture gap is commonly recognized as a risk factor for nonunion. However, no evaluation standard for measuring the fracture gap size has yet been established. In addition, the clinical implications of the fracture gap size have also not been determined so far. This study aims to clarify how we should evaluate fracture gaps when assessing simple femoral shaft fractures with radiographs and to determine the acceptable cut-off value of the fracture gap size in simple femoral shaft fractures. METHOD: A retrospective observational study with a consecutive cohort was conducted at the trauma center of a university hospital. We investigated the fracture gap using postoperative radiography and the postoperative bone union of transverse and short oblique femoral shaft fractures fixed by IMN. The receiver operating characteristic curve analysis was conducted to obtain the fracture gap's mean, minimum, and maximum cut-off values. Fisher's exact test was used at the cut-off value of the most accurate parameter. RESULTS: In the four nonunions among the 30 cases, the analysis using ROC curves revealed that the maximum value had the highest accuracy among the maximum, minimum, and mean values of fracture-gap size. The cut-off value was determined to be 4.14 mm with high accuracy. Fisher's exact test showed that the incidence of nonunion was higher in the group with a maximum fracture gap of 4.14 mm or greater (risk ratio = not applicable, risk difference = 0.57, P = 0.001). CONCLUSION: In simple transverse and short oblique femoral shaft fractures fixed with IMN, the fracture gap on radiographs should be evaluated by the maximum gap in the AP and lateral views. The remaining maximum fracture gap of ≥4.14 mm would be a risk factor for nonunion.

Perioperative risk factors of preterm delivery after fetoscopic laser photocoagulation for twin-twin transfusion syndrome.

OBJECTIVE: To identify risk factors for preterm delivery (PTD) in patients who received fetoscopic laser photocoagulation (FLP) of placental anastomoses for twin-twin transfusion syndrome (TTTS). METHODS: This retrospective cohort study prospectively analyzed and recorded perioperative data in a cohort of patients who had FLP for TTTS, identifying perioperative risk factors for PTD using a Cox proportional hazard regression model. RESULTS: Of 304 patients included, 26 (8.6%) delivered within 4 weeks of FLP. Independent predictors of delivery within 4 weeks of FLP were a history of PTD (hazard ratio [HR]: 5.91, 95% confidence interval [CI]:1.21-28.82, p = 0.03), vaginal bleeding in the second trimester (HR: 6.62, 95% CI: 1.76-24.90, p < 0.01), and amnioreduction ≥1715 mL (HR: 3.16, 95% CI: 1.11-9.05, p < 0.03). CONCLUSION: Patients with a history of PTD, preoperative vaginal bleeding, and amnioreduction ≥1715 mL were more likely to deliver prematurely.

Overweight increases perioperative spinal surgery complications: a single-center retrospective study.

BACKGROUND: The World Health Organization (WHO) defines a person with a body mass index (BMI) greater than or equal to 25 kg/m2 as overweight. Being overweight is a lifestyle-related disease; however, little is known about the impact of overweight on the perioperative complications of orthopedic surgery. This study aimed to define the effect of overweight on the perioperative complications of spinal surgery. METHODS: This retrospective case series study reviewed 269 consecutive patients who underwent spinal surgery. These patients were divided into the overweight (OW) and non-overweight (NOW) groups. Age, BMI, surgical time, blood loss, and perioperative complications were evaluated and compared between the groups. RESULTS: There were 117 patients (43%) in the OW group and 152 (57%) in the NOW group. Cervical surgery was performed in 72 cases, thoracic surgery in 34, and lumbosacral surgery in 159. The surgical time was significantly longer in the OW group than in the NOW group (204.6 ± 98 min vs. 175 ± 75 min; p = 0.01). Blood loss was greater in the OW group than in the NOW group (446.8 ± 447.9 mL vs. 279 ± 296.5 mL; p = 0.00). Durotomy was more frequent in the OW group than in the NOW group (10 vs. 3 cases; p = 0.02). There was no difference in complications other than durotomy. CONCLUSIONS: OW patients had longer surgical time, more blood loss, and more frequent durotomy than NOW patients. These findings indicate that overweight increases perioperative complications of spinal surgery.

A nationwide study of obstetric management and outcomes in premature rupture of membrane at term: Report from the Perinatology Committee, Japan Society of Obstetrics and Gynecology, 2017-2018.

AIM: This nationwide study aimed to investigate the practical management of term premature rupture of membrane (PROM) and its relationship with maternal and neonatal outcomes. METHODS: We conducted a questionnaire survey of 415 facilities participating in the Japan Perinatal Registry Network of the Japan Society of Obstetrics and Gynecology in 2016. The patients were women expecting vaginal birth after PROM at term without clinical chorioamnionitis. We classified the facilities into three groups based on duration of the expectant management after PROM (within 24, 24, and 48 h). Furthermore, we analyzed the association between perinatal outcomes and management protocol using the Japan Perinatal Registry Network Database 2016. RESULTS: Of 415 facilities, 346 (83.4%) completed and returned the survey. Among 231 facilities with management protocols, an interval of 3 days from PROM to delivery was acceptable in 167 facilities (72.3%). One hundred forty-nine facilities (64.5%) responded that they did not perform mechanical cervical dilation, and 90 (39.0%) used oxytocin as a uterotonic irrespective of cervical maturation. The number of hospitals that had a policy to administer antibiotics to Group B streptococcus-positive patients was 211 (91.3%). Neonatal outcomes at birth and the frequency of cesarean section and postpartum fever did not differ among the three groups. CONCLUSIONS: Most facilities in the Japan Perinatal Registry Network managed women at term to delivery within 3 days after PROM with attention to bacterial infection. Expectant management up to 48 h after PROM did not increase the risk of postpartum fever, compared to labor induction immediately after PROM.

Relationship between unremoved cervical polyp in pregnancy and spontaneous preterm birth.

BACKGROUND: Cervical polyps removed during pregnancy have been reported to be associated with preterm birth; however, the association between unremoved cervical polyps and preterm birth has not been elucidated. OBJECTIVE: This study aimed to clarify the relationship between cervical polyps detected before 12 weeks of gestation managed expectantly and spontaneous preterm birth. STUDY DESIGN: This retrospective cohort study included pregnant women who visited a tertiary perinatal center before 12 weeks of gestation between January 2015 and December 2019. The exclusion criteria were as follows: multiple gestations, loss or termination of pregnancy before 12 weeks of gestation, major fetal anomalies, fetal chromosomal abnormalities, fetal demise, having undergone removal of cervical polyps before the first visit to our hospital, and moving to other hospitals before delivery. A vaginal speculum examination was routinely performed during a prenatal visit before 12 weeks of gestation. When a cervical polyp was detected on speculum examination, it was managed expectantly, unless gynecologic malignancy was suspected. Relationships between cervical polyps and spontaneous preterm birth before 34 weeks of gestation were evaluated using logistic regression analysis and Cox proportional-hazards analysis adjusted for known confounders for spontaneous preterm birth. RESULTS: A total of 4172 pregnant women were included, of whom 92 (2.2%) had a cervical polyp detected before 12 weeks of gestation. None of the women underwent polypectomy during pregnancy. The incidence of spontaneous preterm birth before 34 weeks of gestation was higher in pregnant women with cervical polyps than in those without them (5.4% vs 0.7%; P<.01). Logistic regression analysis revealed that cervical polyps were an independent risk factor for spontaneous preterm birth before 34 weeks of gestation (adjusted odds ratio, 4.09; 95% confidence interval, 1.70-9.81; P<.01). The adjusted hazard ratio for spontaneous preterm birth before 34 weeks of gestation among women with vs without cervical polyps was 2.95 (95% confidence interval, 1.32-6.62; P<.01). CONCLUSION: Cervical polyps detected before 12 weeks of gestation managed expectantly are a significant risk factor for spontaneous preterm birth before 34 weeks of gestation.

Incidence of genitourinary injuries in pelvic fractures: A 12-year single-center retrospective study.

OBJECTIVE: This study aimed to determine the epidemiology of genitourinary injuries in pelvic fractures and elucidate the clinical outcomes of patients with pelvic fractures with and without genitourinary injuries at a tertiary trauma center in Japan. METHODS: Patients with pelvic fractures in our tertiary trauma center between May 2009 and April 2021 were retrospectively assessed. The patients' demographics, mechanism of injury, and hospital course details were collected. The outcomes of patients with pelvic fractures with and without genitourinary injuries were compared. RESULTS: Of 402 patients with pelvic fractures, 18 (4.5%) had genitourinary injuries. Falls were the most common mechanisms of injury for all pelvic fractures The incidence of bladder, kidney, urethral, and testis injuries were 2.0%, 1.2%, 1.2%, and 0.5%, respectively. Patients with genitourinary injuries were significantly younger (median age, 26 vs. 51 years; p < 0.001), had a higher rate of intensive care unit admission (94% vs. 58%; p = 0.002), remained hospitalized longer (median duration, 82 vs. 45 days; p < 0.001), and had a longer intensive care unit stay (median duration, 6 vs. 2 days; p < 0.001) when compared to patients without genitourinary injuries. Genitourinary injuries were not associated with in-hospital mortality. CONCLUSIONS: The incidence of genitourinary injuries with pelvic fractures was 4.5%. The presence of genitourinary injuries was associated with a higher rate of intensive care unit admission, longer hospital stay, and longer intensive care unit stay, but it was not associated with in-hospital mortality.

Vacuum phenomenon as a predictor of kyphosis after implant removal following posterior pedicle screw fixation without fusion for thoracolumbar burst fracture: a single-center retrospective study.

BACKGROUND: Posterior pedicle screw fixation without fusion has been commonly applied for thoracolumbar burst fracture. Implant removal is performed secondarily after bone union. However, the occurrence of secondary kyphosis has recently attracted attention. Secondary kyphosis results in poor clinical outcomes. The purpose of this was to determine predictors of kyphosis after implant removal following posterior pedicle screw fixation without fusion for thoracolumbar burst fracture. METHODS: This retrospective study reviewed 59 consecutive patients with thoracolumbar burst fracture who underwent implant removal following posterior pedicle screw fixation without fusion. Inclusion criteria were non-osteoporotic fracture and T11-L3 burst fracture. Old age, sex, initial severe wedge deformity, initial severe kyphosis, and vacuum phenomenon were examined as factors potentially associated with final kyphotic deformity (defined as kyphotic angle greater than 25°) or loss of correction. Logistic regression analysis was performed using propensity score matching. RESULTS: Among the 31 female and 28 male patients (mean age 38 years), final kyphotic deformity was found in 17 cases (29%). Multivariate analysis showed a significant association with the vacuum phenomenon. Loss of correction was found in 35 cases (59%) and showed a significant association with the vacuum phenomenon. There were no significant associations with other factors. CONCLUSIONS: The findings of this study suggest that the vacuum phenomenon before implant removal may be a predictor of secondary kyphosis of greater than 25° after implant removal following posterior pedicle screw fixation without fusion for thoracolumbar burst fracture, but that old age, sex, initial severe kyphosis, and initial severe wedge deformity may not be predictors.

Incidences of complications associated with cervical cerclage by indication of the procedure.

AIM: To investigate the incidence of complications associated with cervical cerclage by indication. METHODS: This was a retrospective cohort study of women with singleton pregnancies who underwent cervical cerclage in a single perinatal center between 2008 and 2019. The participants were divided into three groups according to indication: history-indicated cerclage (HIC) group, ultrasound-indicated cerclage (UIC) group, and physical examination-indicated cerclage (PEIC) group. The incidences of perioperative complications within 2 weeks after the procedure, including intraoperative rupture of membranes, intraoperative bleeding, anesthesia complications, clinical chorioamnionitis, premature rupture of membranes (PROM), preterm delivery, and displacement of the suture, and those of peripartum complications, including difficult suture removal and cervical laceration, for each group were compared using Fisher's exact test or Pearson's chi-square test. Factors associated with severe adverse event, defined as PROM or delivery within 2 weeks after the procedure, were analyzed using multivariate logistic regression analysis. RESULTS: A total of 279 women (HIC, 38; UIC, 96; PEIC, 145) were enrolled. The incidence of perioperative complications was different among the three groups (7.9%, 10.4%, and 27.6%, respectively; p < 0.01), whereas that of peripartum complications was similar (18.4%, 11.5%, and 12.4%, respectively; p = 0.54). Severe adverse events occurred only in PEIC group, with an incidence of 18.6%. The associated factor for severe adverse events in PEIC group was prolapsed membranes into the vagina. CONCLUSIONS: Incidences of perioperative complications of cerclage differed among the indications. Women who underwent PEIC had higher risk of severe adverse events, especially when accompanied with prolapsed membranes into the vagina.

Incidence of chest X-ray abnormalities early in the third trimester of twin pregnancy and its relationship with the subsequent development of preeclampsia.

AIM: To clarify the incidence of abnormal findings on chest X-ray (CXR) early in the third trimester of twin pregnancy and its relationship with the development of preeclampsia and preeclampsia-related diseases. METHODS: This was a retrospective cohort study conducted among women with twin pregnancies who underwent chest radiography for preoperative screening early in the third trimester and delivered at our center at >34 weeks' gestation from 2013 to 2017. The primary outcome was the incidence of positive CXR findings, defined either as cardiomegaly or blunting of the costophrenic angle. The secondary outcome was the incidence of maternal complications, including preeclampsia; hemolytic, elevated liver enzymes, and low platelet syndrome; eclampsia; cerebrovascular disease; and placental abruption. We evaluated the significance of positive CXR findings, in addition to confounding factors, in the subsequent development of preeclampsia. RESULTS: During the study period, 358 twin pregnancies were identified, and 330 were finally enrolled. The incidence of positive CXR findings was 18.2%. The incidence of preeclampsia in the CXR-positive group was 36.7% (22/60), which was significantly higher than that in the CXR-negative group (7.0% [19/270]) (p < 0.01). Moreover, positive CXR findings were independently associated with subsequent preeclampsia (adjusted odds ratio: 9.15, 95% confidence interval: 4.13-20.3). CONCLUSION: In twin pregnancies, the incidence of CXR abnormalities early in the third trimester was 18.2%, even without the development of hypertension. This should be considered a significant risk factor for subsequent preeclampsia.

Efficacy of discontinuing the use of low-dose aspirin at 28 weeks of gestation for preventing preeclampsia.

AIM: Low-dose aspirin (LDA) has been shown to reduce the incidence of preeclampsia (PE). Previous studies have focused on the timing of LDA initiation, but no study to date has assessed the timing of LDA discontinuation. This study aimed to evaluate the effect of LDA when LDA is initiated between 12 and 16 weeks of gestation and continued until 28 weeks of gestation. METHODS: This prospective cohort study with historical controls investigated singleton pregnancies that were at a high risk for PE. High-risk factors were defined as a history of hypertensive disorders of pregnancy, chronic hypertension, diabetes mellitus, autoimmune disease, obesity, and high normal blood pressure in the first trimester. We performed adjustments using propensity score matching (PSM) for each indication of LDA, maternal age, primiparity, and assisted reproductive technology. The primary outcome was the incidence of PE. Secondary outcomes were the incidence of preterm PE, fetal growth restriction (FGR), preterm birth, fetal malformation, and maternal postpartum hemorrhage (PPH). RESULTS: A total of 203 and 543 participants were assigned to the LDA and control group, respectively. After PSM, there was no significant difference in the incidence of PE (22.0% vs. 16.8%; p = 0.20), preterm PE (12.0% vs. 13.1%; p = 0.76), FGR (7.9% vs. 12.0%; p = 0.17), or preterm birth (17.3% vs. 15.7%; p = 0.68). There was also no significant increase in maternal PPH or in the incidence of fetal malformations. CONCLUSION: Discontinuing the use of LDA at 28 weeks of gestation did not result in a lower incidence of PE and FGR.

Impact of the COVID-19 pandemic on a trauma center of a university hospital in Japan.

BACKGROUND: The Coronavirus disease 2019 pandemic caused the Japanese government to declare a State of Emergency on April 7, 2020. The aim of this study is to provide an overview of the effects of the pandemic on surgical cases at a university hospital trauma center. METHODS: An observational study was performed at a trauma center in a tertiary hospital in Tokyo, Japan. The number of surgeries was compared between two periods: a historical control period (Tuesday April 9 to Monday May 27, 2019) and the period of the Japan State of Emergency due to COVID-19 (Tuesday April 7-Monday May 25, 2020). Information on patient age, gender, and surgical diagnosis, site, and procedure was collected for cases operated on in each period. The number of trauma surgeries was compared between the two periods. Data from the two periods were compared statistically. RESULTS: The total number of surgical cases was 151 in the control period and 83 in the COVID-19 period (including no cases with COVID-19), a decrease of 45.0%. There were significantly more surgeries for patients with hip fractures in the COVID-19 period (9 vs. 19, P < 0.001 by Fisher exact test). CONCLUSIONS: During the State of Emergency in Japan, the number of operations for trauma patients at the trauma center decreased, but surgeries for hip fracture increased.

Reelin-Nrp1 Interaction Regulates Neocortical Dendrite Development in a Context-Specific Manner.

Reelin plays versatile roles in neocortical development. The C-terminal region (CTR) of Reelin is required for the correct formation of the superficial structure of the neocortex; however, the mechanisms by which this position-specific effect occurs remain largely unknown. In this study, we demonstrate that Reelin with an intact CTR binds to neuropilin-1 (Nrp1), a transmembrane protein. Both male and female mice were used. Nrp1 is localized with very-low-density lipoprotein receptor (VLDLR), a canonical Reelin receptor, in the superficial layers of the developing neocortex. It forms a complex with VLDLR, and this interaction is modulated by the alternative splicing of VLDLR. Reelin with an intact CTR binds more strongly to the VLDLR/Nrp1 complex than to VLDLR alone. Knockdown of Nrp1 in neurons leads to the accumulation of Dab1 protein. Since the degradation of Dab1 is induced by Reelin signaling, it is suggested that Nrp1 augments Reelin signaling. The interaction between Reelin and Nrp1 is required for normal dendritic development in superficial-layer neurons. All of these characteristics of Reelin are abrogated by proteolytic processing of the six C-terminal amino acid residues of Reelin (0.17% of the whole protein). Therefore, Nrp1 is a coreceptor molecule for Reelin and, together with the proteolytic processing of Reelin, can account for context-specific Reelin function in brain development.SIGNIFICANCE STATEMENT Reelin often exhibits a context-dependent function during brain development; however, its underlying mechanism is not well understood. We found that neuropilin-1 (Nrp1) specifically binds to the CTR of Reelin and acts as a coreceptor for very-low-density lipoprotein receptor (VLDLR). The Nrp1/VLDLR complex is localized in the superficial layers of the neocortex, and its interaction with Reelin is essential for proper dendritic development in superficial-layer neurons. This study provides the first mechanistic evidence of the context-specific function of Reelin (>3400 residues) regulated by the C-terminal residues and Nrp1, a component of the canonical Reelin receptor complex.

Re-evaluation of the predictive value of Quintero staging of twin-twin transfusion syndrome for fetal death after fetoscopic laser photocoagulation.

OBJECTIVE: To elucidate the significance of sonographic indices, including Doppler waveforms, that constitute the Quintero classification for predicting death of the recipient or donor after fetoscopic laser photocoagulation (FLP) for twin-twin transfusion syndrome (TTTS). METHODS: Prospectively collected data of twins who underwent FLP for TTTS were reviewed. Among the abnormal indices of ultrasound performed just before FLP, factors that were significantly associated with fetal and neonatal deaths in the log-rank test, including fetal demise of co-twins and preterm birth before 28 weeks of gestation, were introduced into the Cox proportional-hazards model to calculate risk ratio (RR). RESULTS: We included 235 cases with a prevalence of recipient and donor deaths of 7% and 14%, respectively. In the proportional-hazards model, absent or reversed umbilical artery end-diastolic velocity (UA AREDV) of recipients (n = 7) was independently associated with recipient death (RR = 6.97). In recipients without UA AREDV, reversed ductus venosus (DV) a-wave of recipients (RR = 3.55) was independently associated with recipient death. In donors, UA AREDV with a visible bladder (stage III atypical donor) was independently associated with donor death (RR = 4.24). CONCLUSION: Some individual components of the Quintero stage are associated with death of either recipient or donor twins following FLP.

Fetal Outcomes Associated with the Sequence of Doppler Deterioration in Severely Growth-Restricted Fetuses.

OBJECTIVES: Various patterns of Doppler deterioration exist in fetal growth restriction (FGR). However, the factors that differentiate these patterns are still unknown. The purpose of this study was to clarify the perinatal outcomes and factors to determine the pattern of Doppler deterioration in severe FGR. MATERIALS AND METHODS: We conducted a retrospective cohort study of preterm severe FGR with Doppler abnormality, wherein the clinical features, including maternal characteristics, medical history, and sonographic findings, were compared between the patterns of Doppler deterioration. We used the multivariable logistic regression analyses to identify the factors associated with the pattern of Doppler deterioration. RESULTS: Of 322 eligible fetuses, 143 had Doppler abnormalities. Fetuses with Doppler deterioration from ductus venosus uniquely featured fetal and placental-umbilical abnormalities detected after birth. Gestational age (GA) at diagnosis of FGR and at the first diagnosis of Doppler abnormality in fetuses with Doppler deterioration from middle cerebral artery (MCA) were later than those from umbilical artery. In addition, the factor associated with Doppler deterioration from MCA was 31-week GA at the first diagnosis of Doppler abnormality (adjusted odds ratio [aOR]: 26.7; 95% CI: 8.35-103), not GA at diagnosis of FGR (aOR: 1.82; 95% CI: 0.50-5.96). CONCLUSIONS: Characteristics of each Doppler deterioration pattern might reflect FGR etiology. Undetectable anomalies and umbilical-placental abnormalities were found in fetuses with Doppler deterioration from the ductus venosus. Doppler deterioration from the MCA was observed after 31 weeks of gestation not only in the late-onset FGR but also in the early-onset FGR with normal umbilical artery Doppler findings.

Congenital malformation and hemoglobin A1c in the first trimester among Japanese women with pregestational diabetes.

AIM: To investigate the incidence of major congenital malformations in Japanese women with pregestational diabetes, and to determine the cutoff value of hemoglobin A1c (HbA1c) in the first trimester associated with congenital malformations. METHODS: This retrospective cohort study included singleton pregnancies in Japanese women with pregestational diabetes, including type 1 and type 2 diabetes, and specific types of diabetes due to other causes. The primary outcome was the incidence of major congenital malformations. The secondary outcome was the incidence of all congenital malformations. The cutoff value of HbA1c for congenital malformations was calculated using receiver operating characteristic curve analysis. The adjusted odds ratios (aOR) of major congenital malformations were calculated using multiple logistic regression analyses. RESULTS: This study enrolled 292 patients, including 132 (45.2%) with type 1 diabetes, 156 (53.4%) with type 2 diabetes, and 4 (1.4%) with other specific types. The incidence rates of major congenital malformations and all congenital malformations were 7.2% (21/292) and 12.7% (37/292), respectively. The cutoff value of HbA1c in the first trimester for major malformations and for all congenital malformations was 6.5%. HbA1c ≥ 6.5% was significantly associated with major malformations (aOR 3.5; 95% confidence interval: 1.2-12.6; p = 0.018). CONCLUSION: The incidence of major congenital malformations significantly increased in pregnant Japanese women with HbA1c values of 6.5% or higher. The recommended HbA1c value during the first trimester used in other countries can be applied to pregnant Japanese women.

Prevalence of umbilical artery Doppler waveform abnormality during the early second trimester and the subsequent variation of waveforms in monochorionic diamniotic twin pregnancies: A prospective cohort study.

AIM: To investigate the prevalence of qualitative abnormal umbilical artery Doppler waveforms (Abnormal UA) during the early second trimester and the subsequent variation of waveforms in monochorionic diamniotic (MCDA) twin pregnancies. METHODS: This prospective cohort study included 153 MCDA twin pregnancies. Pulsed Doppler examinations for UA were performed at four points, including the free-loop (FL) and near the placental cord insertion site (CI) of each UA, between 16 and 17 weeks' gestation. Cases were classified into positive diastolic waveforms (Type I), persistent Abnormal UA (Type II), and intermittent Abnormal UA (Type III). When the diastolic velocity in UA Doppler was positive twice after different sequential recordings, the cases were determined to have achieved normalization. Follow-up Doppler examinations of the UA were performed at 24, 28, and 32 weeks' gestation. RESULTS: Of all 153 cases, 38 (25%; 19 Type II and 19 Type III cases) showed Abnormal UA at the first examination. Abnormal UA was detectable at FL in all selective intrauterine growth restriction (sIUGR) cases, whereas it was noted only at CI site in some non-sIUGR cases. Abnormal UA normalized in 12 (63%) Type II and 15 (79%) Type III cases. CONCLUSIONS: A quarter of MCDA twin pregnancies in the early second trimester demonstrated Abnormal UA. In MCDA twins with Abnormal UA between 16 and 17 weeks' gestation, it is preferable to follow them up to consider the possibility of normalization of Abnormal UA as well as features of UA waveforms specific to FL and CI.