'Nausicaa' compression suture: a simple and effective alternative to hysterectomy in placenta accreta spectrum and other causes of severe postpartum haemorrhage.

Postpartum haemorrhage (PPH), especially resulting from placenta accreta spectrum (PAS), has become a worldwide concern in maternity care. We describe a novel method of uterine compression sutures (the 'Nausicaa' technique) as an alternative to hysterectomy for patients who have suffered from major PPH. We applied this technique in 68 patients with major PPH during caesarean section (including 43 patients with PAS, 20 patients with placenta praevia totalis, and five patients with uterine atony), and none of these patients required further hysterectomy. We conclude that our Nausicaa suture is a simple and feasible alternative to hysterectomy in patients suffering from major PPH.

Microdeletions/duplications involving TBX1 gene in fetuses with conotruncal heart defects which are negative for 22q11.2 deletion on fluorescence in-situ hybridization.

OBJECTIVES: Conotruncal heart defects (CTD) are associated with del22q11.2 syndrome, which is often diagnosed by fluorescence in-situ hybridization (FISH). However, in those negative for del22q11.2 on FISH, the etiology is usually obscure. We aimed to use high-resolution array comparative genomic hybridization (array CGH) to clarify the underlying genetic causes in these cases. METHODS: In this retrospective study, fetal samples of amniocytes or fibroblasts, taken either for prenatal diagnosis by amniocentesis or for postnatal survey after termination of pregnancy, were obtained from 45 fetuses with CTD and were investigated by cytogenetic analysis including karyotyping and FISH for del22q11.2 syndrome. Eight fetuses with no findings on karyotyping and FISH were investigated further by array CGH, real-time quantitative polymerase chain reaction (qPCR) and Sanger sequencing of TBX1. RESULTS: Array CGH revealed that three of the eight fetuses carried submicroscopic genomic imbalances. Of these, two cases showed similar small microdeletions/duplications in 22q11.2 (one 0.85 kb microdeletion and one 8.51 kb microduplication). The minimal shared region spanned exon 2 of TBX1, a candidate gene responsible for cardiovascular defects in del22q11.2 syndrome. In all eight cases, the array CGH results were confirmed by qPCR, and Sanger sequencing did not detect other molecular pathologies. CONCLUSION: Our findings indicate an association between TBX1 variations and fetal CTD. The results also demonstrate the power of array CGH to further scrutinize the critical gene(s) of del22q11.2 syndrome responsible for heart defects. Array CGH apparently has diagnostic sensitivity superior to that of FISH in fetuses with CTD associated with del22q11.2 (and dup22q11.2) syndrome.

Effects of increased image noise on image quality and quantitative interpretation in brain CT perfusion.

BACKGROUND AND PURPOSE: There is a desire within many institutions to reduce the radiation dose in CTP examinations. The purpose of this study was to simulate dose reduction through the addition of noise in brain CT perfusion examinations and to determine the subsequent effects on quality and quantitative interpretation. MATERIALS AND METHODS: A total of 22 consecutive reference CTP scans were identified from an institutional review board-approved prospective clinical trial, all performed at 80 keV and 190 mAs. Lower-dose scans at 188, 177, 167, 127, and 44 mAs were generated through the addition of spatially correlated noise to the reference scans. A standard software package was used to generate CBF, CBV, and MTT maps. Six blinded radiologists determined quality scores of simulated scans on a Likert scale. Quantitative differences were calculated. RESULTS: For qualitative analysis, the correlation coefficients for CBF (-0.34; P < .0001), CBV (-0.35; P < .0001), and MTT (-0.44; P < .0001) were statistically significant. Interobserver agreements in quality for the simulated 188-, 177-, 167-, 127-, and 44-mAs scans for CBF were 0.95, 0.98, 0.98, 0.95, and 0.52, respectively. Interobserver agreements in quality for the simulated CBV were 1, 1, 1, 1, and 0.83, respectively. For MTT, the interobserver agreements were 0.83, 0.86, 0.88, 0.74, and 0.05, respectively. For quantitative analysis, only the lowest simulated dose of 44 mAs showed statistically significant differences from the reference scan values for CBF (-1.8; P = .04), CBV (0.07; P < .0001), and MTT (0.46; P < .0001). CONCLUSIONS: From a reference CTP study performed at 80 keV and 190 mAs, this simulation study demonstrates the potential of a 33% reduction in tube current and dose while maintaining image quality and quantitative interpretations. This work can be used to inform future studies by using true, nonsimulated scans.

Mutations in monoamine oxidase (MAO) genes in mice lead to hypersensitivity to serotonin-enhancing drugs: implications for drug side effects in humans.

A possible side effect of serotonin-enhancing drugs is the serotonin syndrome, which can be lethal. Here we examined possible hypersensitivity to two such drugs, the serotonin precursor 5-hydroxy-L-tryptophan (5-HTP) and the atypical opioid tramadol, in mice lacking the genes for both monoamine oxidase A (MAOA) and MAOB. MAOA/B-knockout (KO) mice displayed baseline serotonin syndrome behaviors, and these behavioral responses were highly exaggerated following 5-HTP or tramadol versus baseline and wild-type (WT) littermates. Compared with MAOA/B-WT mice, baseline tissue serotonin levels were increased ∼2.6-3.9-fold in MAOA/B-KO mice. Following 5-HTP, serotonin levels were further increased ∼4.5-6.2-fold in MAOA/B-KO mice. These exaggerated responses are in line with the exaggerated responses following serotonin-enhancing drugs that we previously observed in mice lacking the serotonin transporter (SERT). These findings provide a second genetic mouse model suggestive of possible human vulnerability to the serotonin syndrome in individuals with lesser-expressing MAO or SERT polymorphisms that confer serotonergic system changes.

Clinical utility of array comparative genomic hybridisation for prenatal diagnosis: a cohort study of 3171 pregnancies.

OBJECTIVE: To evaluate the clinical value of prenatal array comparative genomic hybridisation (CGH) in screening for submicroscopic genomic imbalances. DESIGN: Cross-sectional study. SETTING: Tertiary referral centre. POPULATION: From June 2008 to February 2011, 3171 fetuses underwent prenatal array CGH testing and karyotyping at the National Taiwan University Hospital. Indications for invasive prenatal diagnosis included abnormal karyotype, abnormal ultrasound, advanced maternal age and parental anxiety. METHODS: In all, 2497 fetuses were screened with 1-Mb resolution bacterial artificial chromosome array-based CGH, and 674 fetuses with 60-K oligonucleotide array-based CGH. Multiplex ligation-dependent probe amplification, fluorescence in situ hybridization, or 105-K oligonucleotide array CGH provided further confirmation. MAIN OUTCOME MEASURE: Copy number variations identified by array CGH. RESULTS: Array CGH detected numerical chromosome anomalies in 37 (1.2%) fetuses, microdeletion/duplication in 34 (1.1%) fetuses, large deletion/duplication in 13 (0.4%) fetuses, benign copy number changes in 13 (0.4%) fetuses and variation of unknown clinical significance in five (0.2%) fetuses. Array CGH was effective in identifying submicroscopic genomic imbalance in fetuses with de novo balance translocations (2/17, 1.8%), supernumerary marker chromosomes (3/6, 50%), and abnormal prenatal ultrasound findings (33/194, 17.0%). Array CGH detected microdeletions/duplications in 12 fetuses with normal karyotype. CONCLUSION: Prenatal array CGH is effective in screening for submicroscopic genomic imbalance. Array CGH may add 8.2% to the diagnostic field, compared with conventional karyotyping, for fetuses with abnormal ultrasound results, and is particularly useful in fetuses with karyotypic balanced translocation or marker chromosomes. There is a 0.52% baseline risk of submicroscopic genomic imbalance, even in women with an uneventful prenatal examination.

Experimental treatment of bilateral fetal chylothorax using in-utero pleurodesis.

OBJECTIVE: To assess the use and efficacy of in-utero pleurodesis for experimental treatment of bilateral fetal chylothorax. METHODS: This was a study of 78 fetuses with bilateral pleural effusion referred to three tertiary referral centers in Taiwan between 2005 and 2009. Fetuses were karyotyped following amniocentesis and the lymphocyte ratio in the pleural effusion was determined following thoracocentesis. Forty-nine (62.8%) fetuses had a normal karyotype and were recognized to have fetal chylothorax; of these, 45 underwent intrapleural injection of 0.1KE OK-432 per side per treatment. We evaluated clinical (hydrops vs. no hydrops) and genetic (mutations in the reported lymphedema-associated loci: VEGFR3, PTPN11, FOXC2, ITGA9) parameters, as well as treatment outcome. Long-term survival was defined as survival to 1 year of age. RESULTS: The overall long-term survival rate (LSR) was 35.6% (16/45); the LSR for non-hydropic fetuses was 66.7% (12/18) and for hydropic fetuses it was 14.8% (4/27). If we included only fetuses with onset of the condition in the second trimester, excluding those with onset in the third trimester, the LSR decreased to 29.4% (10/34). Notably, 29.6% (8/27) of hydropic fetuses had mutations in three of the four loci examined. CONCLUSIONS: OK-432 pleurodesis appeared to be an experimental alternative to the gold-standard technique of thoracoamniotic shunting in non-hydropic fetal chylothorax. In hydropic fetuses, pleurodesis appeared less effective.

Genetic evaluation and management of fetal chylothorax: review and insights from a case of Noonan syndrome.

Fetal chylothorax is one of a very few syndromes that can be treated in utero with thoracoamniotic shunting or pleurodesis by OK-432 as two major therapeutic modalities. We report on a fetus with Noonan syndrome and a missense mutation c.182A > C (p.Asp61Ala) of PTPN11 who responded poorly to antenatal pleurodesis by OK-432. Based on our previous publication and this case study, we propose that fetal chylothorax of a distinct genetic origin may respond poorly to OK-432 pleurodesis.

Role of three-dimensional power Doppler in the antenatal diagnosis of placenta accreta: comparison with gray-scale and color Doppler techniques.

OBJECTIVE: To assess the role of three-dimensional (3D) power Doppler in the antenatal diagnosis of placenta accreta and compare its diagnostic performance with gray-scale and color Doppler ultrasonography. METHODS: One hundred and seventy pregnant women with persistent placenta previa totalis (after 28 weeks' gestation) were prospectively enrolled into this study. Gray-scale transabdominal ultrasound examination was performed to detect loss of the subendometrial echolucent zone and other abnormalities suggestive of placenta accreta. Color flow mapping was used to scan the whole placenta to detect any newly formed vessels at the serosa-bladder border or the presence of abnormal lacunae. Finally a targeted examination of angioarchitecture in the basal and lateral views of the placenta was carried out using 3D power Doppler. The ultrasound findings were analyzed with reference to the final diagnosis made during Cesarean delivery. RESULTS: Placenta accreta and its variants (including increta and percreta) were confirmed in 39 patients at the time of Cesarean delivery. Based on receiver-operating characteristics analysis, 'numerous coherent vessels' visualized using 3D power Doppler in the basal view was the best single criterion for the diagnosis of placenta accreta, with a sensitivity of 97% and a specificity of 92%. If we considered the presence of at least one criterion to be diagnostic when using each ultrasound technique, then 3D power Doppler would have the best positive predictive value (76%), followed by gray-scale (51%) and color Doppler (47%). The majority of patients with placenta accreta showed multiple characteristic features on ultrasound imaging. In contrast, those patients with a false-positive diagnosis (i.e. the final diagnosis was placenta previa alone) tended to show isolated ultrasound markers of the condition. CONCLUSION: 3D power Doppler may be useful as a complementary technique for the antenatal diagnosis or exclusion of placenta accreta.

Changes in uterine blood flow following laparoscopic myomectomy with or without uterine artery ligation on two- and three-dimensional power Doppler ultrasound.

OBJECTIVE: To evaluate differences in uterine perfusion following laparoscopic myomectomy with or without uterine artery ligation (UAL). METHODS: From November 2005 to July 2007, we enrolled prospectively 105 women with symptomatic myomas who were scheduled to undergo laparoscopic myomectomy (57 with UAL (study group) and 48 without (control group)). Power Doppler ultrasound was used to evaluate uterine artery resistance (RI) and pulsatility (PI) indices and peak systolic velocity (PSV) and three-dimensional (3D) power Doppler ultrasound was used to obtain vascularization (VI), flow (FI) and vascularization flow (VFI) indices of the uterine tissue, which were calculated by VOCAL (Virtual Organ Computer-aided AnaLysis) software. RESULTS: Characteristics of the myomas, operative time and duration of hospital stay were comparable between the two groups, whereas the median (range) of estimated blood loss (50 (50-200) vs. 100 (50-900) mL, P = 0.001) and the frequency of excessive bleeding of > 500 mL (0% vs. 10%, P = 0.018) were significantly lower in the study group. The RI, PI and PSV were comparable between the two groups preoperatively, significantly lower in the study group 1 week after surgery (0.69 vs. 0.74, 1.31 vs. 1.76, and 34.08 vs. 47.49, respectively, P < 0.05), and comparable again 3 months later. The myometrial VI and VFI decreased after surgery and all three 3D power Doppler indices of the study group were similar to those of the control group throughout the study period. CONCLUSION: Concurrent UAL during laparoscopic myom- ectomy reduces the intraoperative blood loss and frequency of excessive bleeding without permanently compromising uterine perfusion.

'Big-eyed frog' sign on spatiotemporal image correlation (STIC) in the antenatal diagnosis of transposition of the great arteries.

OBJECTIVE: To determine the value of simultaneous visualization of the cross-sectional view of both atrioventricular (AV) valves, the pulmonary artery and the aorta (en-face view of the AV valves and great vessels) in the identification of fetuses with transposition of the great arteries (TGA). METHODS: This was a retrospective analysis of volume datasets obtained with the spatiotemporal image correlation (STIC) technique from 56 fetuses with and 30 fetuses without congenital heart defects. Volume datasets were reviewed offline to compare the en-face view of the AV valves and great vessels between fetuses with normal echocardiography and those with TGA. RESULTS: The en-face view of both AV valves and great vessels in fetuses with TGA displayed the main pulmonary artery situated side-by-side with the aorta ('big-eyed frog' sign). In contrast, fetuses with normal hearts did not have this characteristic sonographic sign. This novel sonographic sign also helped to identify additional cases of TGA in 17 fetuses with complex heart defects. CONCLUSION: The big-eyed frog sign may prove helpful in the prenatal diagnosis of TGA.

Kinetics and functional assay of liver repopulation after human cord blood transplantation.

BACKGROUND AND AIMS: To evaluate donor cell engraftment and the kinetics of cell repopulation in the injured mouse liver following human umbilical cord blood cell transplantation. METHODS: Nonobese diabetic/severe immunodeficient mice were treated with allyl alcohol to induce liver injury. Twenty-four hours later, umbilical cord blood derived mononuclear cells were transplanted by intra-splenic injection. Mice were sacrificed from 1 to 180 days after transplantation. Temporal changes in the ratio of human cells and fluorescence counts of human sex-determining region Y alleles in mouse liver were determined to evaluate the kinetics of cell repopulation. Mouse liver and sera were examined for the presence of human albumin. RESULTS: Human cell repopulation was extremely rapid in the first week following transplantation, with a doubling time of 1.16-1.39 days apparent. Thereafter cell doubling rate slowed significantly. Cells displaying characteristics of human hepatocytes were still evident at 180 days. Human albumin was detected in mouse liver and sera. CONCLUSION: These findings confirm those from previous studies demonstrating that cells derived from human umbilical cord blood have the capacity to differentiate into cells with human hepatocyte characteristics in mouse liver following injury. Moreover, the detailed information collected regarding the kinetics of human cell repopulation in mouse liver will be of relevance to future studies examining the use of umbilical cord blood cells in liver transplantation therapy.