Birth outcomes following pelvic ring injury: A retrospective study.

OBJECTIVE: To report obstetric outcomes in pregnant women with previous pelvic ring injury (PRI) and investigate the correlation between residual pelvic deformity and the mode of delivery. DESIGN: Retrospective cohort study. SETTING: Single medical centre in Taiwan. POPULATION: Forty-one women with PRI histories from 2000 to 2021 who subsequently underwent pregnancy and delivery. METHODS: All patients had complete PRI treatment and radiological follow up for at least 1 year. The demographic data, radiological outcomes after PRI and obstetric outcomes were collected to investigate the potential factors of delivery modes using non-parametric approaches and logistic regression. Caesarean section (CS) rates among different subgroups were reported. MAIN OUTCOME MEASURES: Comparisons of demographic data and radiological outcomes (Matta/Tornetta criteria and Lefaivre criteria) after PRI among patients who had subsequent pregnancy and underwent vaginal deliveries (VD) or CS. RESULTS: There were 14 VD and 27 CS in 41 patients. Nine patients underwent CS because of their PRI history, 12 patients underwent CS for other obstetric indications and 20 underwent trial of labour. Based on the logistic regression model, retained trans-iliosacral implants did not significantly increase the risk of CS (odds ratio [OR] 1.20; 95% CI 0.17-8.38). Higher pelvic asymmetry value by Lefaivre criteria was a potential risk factor for CS after previous PRI (OR 1.52; 95% CI 1.043-2.213). CONCLUSIONS: VD is possible after PRI. Retained trans-iliosacral implants do not affect the delivery outcome. Residual pelvic asymmetry after PRI by Lefaivre criteria is a potential risk factor for CS.

Trans-arterial embolization for intractable primary postpartum hemorrhage caused by arterial aneurysms with arteriovenous fistulas in the lower vagina bilaterally: a case report.

Failure of conservative management for controlling postpartum hemorrhage (PPH) is not uncommon, particularly when PPH is caused by vascular lesions. Awareness of this possibility and initiating timely trans-arterial embolization (TAE) are essential for improving the outcome. Herein, we describe the case of a 34-year-old woman presenting with arterial aneurysms with arteriovenous fistulas in the lower vagina bilaterally, which caused intractable PPH. Conservative management failed to resolve the PPH; however, TAE successfully controlled the bleeding, and the patient recovered smoothly. Knowledge of this possible etiology for intractable PPH is crucial for timely TAE. This case report aims to highlight the pivotal role of TAE in detecting and treating this unusual cause of PPH.

Prenatal diagnosis of Simpson-Golabi-Behmel syndrome type 1 with an 814 kb Xq26.2 deletion with the initial presentation of a thick nuchal fold.

OBJECTIVE: Simpson-Golabi-Behmel syndrome type 1 (SGBS1) is a rare X-linked recessive disorder characterized by overgrowth and multiple anomalies. Most clinical diagnoses of SGBS1 are made postnatally. We present the case of a pregnant woman in whom the fetus presented with a thick nuchal fold 5.6 mm at 15 weeks of gestation, leading to the prenatal diagnosis of SGBS1 with Xq26.2 (133408101-134221889) deletion. CASE REPORT: We report the case of a 34-year-old pregnant woman with the initial presentation of fetal thick nuchal fold 5.6 mm at 15 weeks of gestation. Amniocentesis of the fetal karyotype revealed a normal 46, XY, and single nucleotide polymorphism array showed Xq26.2 (133408101-134221889) deletion. Prenatal ultrasound at 21 weeks of gestation revealed a thick nuchal fold, hepatomegaly, nephromegaly, congenital diaphragmatic hernia, hypospadias, and polyhydramnios. Fetal magnetic resonance imaging revealed hepatomegaly, nephromegaly, congenital diaphragmatic hernia, and right lung hypoplasia. The woman had her pregnancy terminated at 24 weeks of gestation. The proband had a general appearance of low-set ears, hypertelorism, a large tongue, and hypospadias and some unique findings on autopsy, including hepatomegaly, right hiatal hernia, liver extensive extramedullary hematopoiesis, kidney marked congestion, and focal hemorrhage. DISCUSSION: The main prenatal ultrasound findings that alert clinical doctors about the possible diagnosis of SGBS1 included macrosomia, polyhydramnios, organomegaly, renal malformations, congenital diaphragmatic hernia, and cardiac anomalies. Our case underscores the importance of fetal karyotyping combined with single nucleotide polymorphism array when a thick nuchal fold is found. Genetic counseling is essential in SGBS1, and prenatal testing or preimplantation testing for subsequent pregnancies is necessary to identify possible pathogenic variants.

Clinical Characteristics of Infants with Symptomatic Congenital and Postnatal Cytomegalovirus Infection-An 11-Year Multicenter Cohort Study in Taiwan.

(1) Background: Cytomegalovirus (CMV) infection is a prevalent viral disease among infants. The prevalence typically ranges from 0.2% to 2.4% among all newborns. There are limited data regarding the demographic characteristics of infants with symptomatic CMV infections. (2) Methods: In this retrospective cohort study using the Chang Gung Memorial Hospital multicenter database, infants with CMV infection determined by a positive urine culture, positive blood polymerase chain reaction assay or positive immunoglobulin M result for CMV from 2011 through 2021 were included. Clinical characteristics at initial diagnosis, management and outcomes were investigated. Congenital CMV (cCMV) infection is diagnosed within three weeks after birth; postnatal CMV (pCMV) is diagnosed when CMV is detected after the first 3 weeks of life. (3) Results: Among the 505 CMV-infected infants identified, 272 were included in the analysis. According to the age at initial presentation, 21 infants had cCMV infection and 251 had pCMV infection. Higher incidences of prematurity and being small for gestational age and a lower Z score for weight at diagnosis were observed in the cCMV group. While thrombocytopenia (61.9%) was the leading presentation in the cCMV group, hepatitis (59.8%) and prolonged jaundice (21.9%) were more common in the pCMV group. (4) Conclusions: Utilizing an 11-year multicenter database, we demonstrated the characteristics of infants with CMV infection in Taiwan and highlighted the demographic disparities and differing symptoms between the cCMV and pCMV groups. These findings emphasize the necessity for future research to refine screening policies, explore treatment options, and establish follow-up protocols for affected infants.

Clinical outcomes and maternal associated conditions between antepartum and postpartum-onset of peripartum cardiomyopathy.

OBJECTIVE: Peripartum cardiomyopathy (PPCM) developed from late pregnancy to five months after delivery. Women with PPCM have the risk of mortality or non-recovered cardiac function. We aimed to investigate women with PPCM in Taiwan. MATERIALS AND METHODS: The retrospective study recruited patients with PPCM from January 2002 to October 2018 in a tertiary center. We evaluated the presentations, onset, associated conditions, maternal and fetal outcomes, follow-up cardiac function, and subsequent pregnancies. The clinical data were compared between antepartum and postpartum-onset of PPCM. RESULTS: Thirty women were identified and seventeen (56.6%) patients were antepartum-onset. The delivery time, ranged from 26 to 40 weeks, was mostly at 35 weeks. Twenty-one patients had cardiac function follow-up and seven (33.3%) were non-recovered in six months. The associated conditions of PPCM included age >30, primiparity, preeclampsia or hypertension, obesity, twin pregnancy, and tocolysis. The maternal characteristics and associated conditions were not significant different, but early preterm (32.8 ± 3.6 vs. 35.5 ± 2.4 weeks, p = 0.042) and lower Apgar scores in one (7 vs. 9, p = 0.002) and 5 min (9 vs. 10, p = 0.005) were observed in the antepartum-onset group. CONCLUSION: In conclusion, PPCM commonly occurred around 35 weeks of gestation, ranged from 26 to 40 weeks. Additionally, there were risks of early preterm and low Apgar scores in women with antepartum-onset of PPCM.

Maternal-Neonatal Outcomes of Obstetric Deliveries Performed in Negative Pressure Isolation Rooms during the COVID-19 Omicron Variant Pandemic in Taiwan: A Retrospective Cohort Study of a Single Institution.

Objective: To investigate the maternal−neonatal outcomes of obstetric deliveries performed in negative pressure isolated delivery rooms (NPIDRs) during the coronavirus disease 2019 (COVID-19) omicron variant pandemic period in a single tertiary center in northern Taiwan. Methods: Confirmed positive and suspected-positive COVID-19 cases delivered in NPIDRs and COVID-19-negative mothers delivered in conventional delivery rooms (CDRs) in the period of 1 May 2022 to 31 May 2022 during the COVID-19 omicron variant pandemic stage were reviewed. The maternal−neonatal outcomes between the two groups of mothers were analyzed. All deliveries were performed following the obstetric and neonatologic protocols conforming to the epidemic prevention regulations promulgated by the Taiwan Centers for Disease Control (T-CDC). Multiple gestations, deliveries at gestational age below 34 weeks, and major fetal anomalies were excluded from this study. Results: A total of 213 obstetric deliveries were included. Forty-five deliveries were performed in NPIDRs due to a positive COVID-19 polymerase chain reaction (PCR) test (n = 41) or suspected COVID-19 positive status (n = 4). One hundred and sixty-eight deliveries with negative COVID-19 PCR tests were performed in CDRs. There was no statistical difference in maternal characteristics between the two groups of pregnant women. All COVID-19-confirmed cases either presented with mild upper-airway symptoms (78%) or were asymptomatic (22%); none of these cases developed severe acute respiratory syndrome. The total rate of cesarean section was not statistically different between obstetric deliveries in NPIDRs and in CDRs (38.1% vs. 40.0%, p = 0.82, respectively). Regardless of delivery modes, poorer short-term perinatal outcomes were observed in obstetric deliveries in NPIDRs: there were significant higher rates of neonatal respiratory distress (37.8% vs. 10.7%, p < 0.001, respectively), meconium-stained amniotic fluid (22.2% vs. 4.2%, p < 0.001, respectively) and newborn intensive care unit admission (55.6% vs. 8.3%, p < 0.001, respectively) in obstetric deliveries performed in NPIDRs than in CDRs. Maternal surgical outcomes were not significantly different between the two groups of patients. There was no vertical transmission or nosocomial infection observed in COVID-19 confirmed cases in this study period. Conclusions: Our study demonstrates that obstetric deliveries for positive and suspected COVID-19 omicron-variant cases performed in NPIDRs are associated with poorer short-term perinatal outcomes. Reasonable use of personal protective equipment in NPIDRs could effectively prevent nosocomial infection during obstetric deliveries for pregnant women infected with the COVID-19 omicron variant.

Absence of chronicity in infants born to immunized mothers with occult HBV infection in Taiwan.

BACKGROUND & AIMS: In the Taiwanese population born in the universal vaccination era, HBsAg carrier rates have fallen below 2%, while approximately 5% develop occult hepatitis B infection (OBI). However, the potential for transmission from mothers with OBI to their infants has not been well studied. We aimed to investigate whether mothers with OBI could transmit HBV to their babies. METHODS: A total of 253 pregnant women who were born after July 1986 and had been fully vaccinated against HBV during infancy were recruited from a tertiary hospital in Northern Taiwan. HBV serology and DNA levels were determined. Babies born to mothers with OBI were followed-up until 1 year of age. The surface genes were sequenced. RESULTS: HBV infection was documented in 18 vaccinated mothers, 2 of whom were HBsAg-reactive (0.79 %). Seventeen were positive for HBV DNA, among whom 16 (6.32%) presented with OBI with a median DNA level of 145 IU/ml (interquartile range: 37.8-657.3 IU/ml). Eleven babies born to 10 mothers with OBI were recruited. Three babies were HBsAg-reactive, and 2 were positive for HBV DNA (17.0 and 212.0 IU/ml). Seven mothers with OBI carried multiple surface gene variants. Two transiently infected babies harbored variants originating from their mother's HBV quasi-species. All infants received complete hepatitis B vaccines. At 12 months of age, none of the babies were positive for HBsAg or HBV DNA. CONCLUSIONS: It was possible for mothers with OBI to transmit HBV to their babies, who consequently harbored surface gene variants originating from their mothers' minor variants. Viremia was cleared 1 year after completing the hepatitis B vaccination series. LAY SUMMARY: Since initiating the hepatitis B vaccination program in Taiwan, the rate of young individuals (i.e. born after 1986) carrying the HBV surface antigen has fallen below 2%, although around 5% of vaccinated individuals develop occult HBV infections. Herein, we show that pregnant mothers with occult HBV infections can transmit HBV to their offspring. However, no infant had sustained infection at 1 year of age having completed a full HBV vaccination series.

Hysteroscopic removal, with or without laparoscopic assistance, of first-trimester cesarean scar pregnancy.

OBJECTIVE: To demonstrate the implementation and potential benefits of hysteroscopic removal, with or without concomitant laparoscopic assistance, of first-trimester cesarean scar pregnancies (CSPs). DESIGN: Patients with prior cesarean deliveries may have scar formation at the muscular wall of the uterine isthmus, resulting in a cesarean scar defect (CSD), also known as an isthmocele or diverticulum. When implantation of a trophoblast occurs at the CSD, a CSP develops, and with progression onto higher gestational age, it carries risks for serious complications, such as placenta previa spectrum, life-threatening bleeding, uterine rupture, and cesarean hysterectomy. Therefore, early termination is often recommended. Given that the chorionic frondosum only penetrates the decidual basalis layer during the first trimester and does not invade the distal myometrial segment until early second trimester, operative hysteroscopy can be a reliable and efficient treatment modality for early intervention. This narrated video features the systematic approach and surgical management for patients with first-trimester CSPs. SETTING: Academic tertiary hospital. PATIENT(S): Three multiparous women between 34 and 38 years of age diagnosed with CSPs within the first trimester. INTERVENTION(S): Initial assessment with transvaginal ultrasonography and color Doppler flow identifies the site of implantation and measures the residual myometrial thickness (RMT), which are important parameters for classifying the CSPs into type I or type II. Type I CSPs often present at an earlier gestational age, have a thicker RMT, and grow toward the uterine cavity, while type II CSPs are frequently noted at a higher gestational age, have a thinner RMT, demonstrate obvious scar dehiscence, and often invade toward the bladder. The patients received either operative hysteroscopy alone or with concomitant laparoscopic assistance and repair of CSD dehiscence. For all hysteroscopic operations, misoprostol (200 µg) was given 4 hours before the procedure while oxytocin (20 U in 1000 mL isotonic solution, intravenous infusion) was infused immediately after removal of the placental tissue. For laparoscopic excision and repair of the dehiscent scar, local injection of 5 mL terlipressin acetate (1 mg) was added before the initiation of laparoscopic CSD excision. MAIN OUTCOME MEASURE(S): Appraisal of the parameters used for preoperative assessment, the efficacy of the surgical procedures, and the intention to minimize the associated risks and morbid sequalae were evaluated. RESULT(S): Most of the type I CSPs or type II CSPs with gestational age <8 weeks and RMT >3 mm can be successfully treated with operative hysteroscopy alone. In contrast to blind dilatation and curettage, operative hysteroscopy offers direct visualization to ensure complete removal of the chorionic villi, which can occasionally be buried deep within the concavity of the CSD. It is worth noting that gently sweeping the decidua basalis from the myometrium with the loop resectoscope is more than enough to separate the chorionic villi within and completely displace the placental tissues without causing massive hemorrhage. For type II CSPs in late first-trimesters showing distended CSDs and diminished RMT, laparoscopy can be established before the hysteroscopic procedure for better surveillance and to prevent inadvertent myometrial perforation. Then, hysteroscopic removal of CSP can further induce uterine contractions to help reduce blood loss during subsequent laparoscopic repair of CSD. CONCLUSION(S): Accurate diagnosis and timely management of CSPs during the first trimester are crucial for preventing significant morbidities associated with advanced gestational age. Operative hysteroscopy offers the benefit of direct visualization for competent detachment of the decidua basalis of the CSP from the steep concavity of the CSD. Furthermore, the employment of laparoscopy for type II CSPs helps avoid inadvertent complications related to the thin RMT and allows concomitant repair of the extensive dehiscence.

Association between intrauterine growth restriction and patent ductus arteriosus: Use of a dichorionic twin pregnancy model.

OBJECTIVE: To evaluate the association between intrauterine growth restriction (IUGR) and the incidence of fetuses with patent ductus arteriosus (PDA) and Hemodynamically significant PDA (Hs-PDA) in dichorionic twins (DC) with selective IUGR. MATERIALS AND METHODS: This is an observational cohort study and retrospective case assessment, involved twins born at Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan between 2013 and 2018. DC twins with selective IUGR (sIUGR) were defined as the presence of a birth weight discordance of >25% and a smaller twin with a birth weight below the tenth percentile. PDA was diagnosed using echocardiography between postnatal day 3 and 7. Hs-PDA was defined as PDA plus increased pulmonary circulation, poor systemic perfusion, cardiomegaly, pulmonary edema, or hypotension requiring pharmacotherapeutic intervention. RESULT: A total of 1187 twins were delivered during the study period, and 53 DC twins with selective IUGR were included in this study. DC twins with PDA have higher rate of preterm birth, lower gestational age of delivery, and lower mean birth weight of both twins compared with DC twins without PDA. In a comparison of the sIUGR twin with the appropriate for gestational age co-twin, both the incidences of PDA (28.30% vs. 7.55%, respectively; P = 0.003) and Hs-PDA (24.53% vs. 5.66%, respectively; P = 0.002) were higher in sIUGR fetuses than in the appropriate for gestational age co-twins. Small gestational age of delivery was the only variable to predict PDA and Hs-PDA [p = 0.002, Odds ratio = 0.57 (0.39-0.82), p = 0.009, Odds ratio = 0.71 (0.55-0.92), respectively]. CONCLUSION: An analysis of dichorionic twins with sIUGR indicated that IUGR increased the risk of PDA and hemodynamically significant PDA.

Effect of Hydrocortisone on Angiotensinogen (AGT) Mutation-Causing Autosomal Recessive Renal Tubular Dysgenesis.

We has identified a founder homozygous E3_E4 del: 2870 bp deletion + 9 bp insertion in AGT gene encoding angiotensinogen responsible for autosomal recessive renal tubular dysgenesis (ARRTD) with nearly-fatal outcome. High-dose hydrocortisone therapy successfully rescued one patient with an increased serum Angiotensinogen (AGT), Ang I, and Ang II levels. The pathogenesis of ARRTD caused by this AGT mutation and the potential therapeutic effect of hydrocortisone were examined by in vitro functional studies. The expression of this truncated AGT protein was relatively low with a dose-dependent manner. This truncated mutation diminished the interaction between mutant AGT and renin. The truncated AGT also altered the glucocorticoid receptor (GR)-dependent transactivation, indicating that AGT may affect the development of proximal convoluted tubule by alteration of glucocorticoid-dependent transactivation. In hepatocytes, hydrocortisone increased the AGT level by accentuating the stability of mutant AGT and increasing its binding with renin. Therefore, hydrocortisone may exert the therapeutic effect through the enhanced stability and interaction with renin of truncated AGT in patients carrying this AGT mutation.

Interstitial ectopic pregnancy: A more confident diagnosis with three-dimensional sonography.

OBJECTIVE: To present a confident tool for the diagnosis of interstitial ectopic pregnancy. 3-Dimensional US helps to reach a more proper diagnosis and enables to arrange therapeutic and surgical strategies. CASE REPORT: A 36-year-old, gravida 4 para 2, woman was referred from the local medical department in the suspicion of ectopic pregnancy. Transabdominal ultrasound revealed an empty uterine cavity but an 8-week-old gestational sac located eccentrically on the right side of the uterine fundus. The Three-dimensional sonography (3D US) demonstrated a gestational sac (GS) over the right cornual region separated from the endometrial cavity. Interstitial pregnancy was impressed. Laparoscopic surgery was then arranged. After entering the pelvic cavity, a bulging mass was found over the utero-tubal junction, compatible with interstitial pregnancy. The wedge resection of interstitial ectopic pregnancy and right salpingectomy were undertaken. The patient was discharged within 2 days after the surgery. CONCLUSION: The conventional sonography still remained the primary tool to diagnose the ectopic pregnancy, but 3D US played an indispensable role in demonstrating the precise location of GS. Interstitial ectopic pregnancy was symptomatically late in gestation and rupture of an interstitial pregnancy causes catastrophic consequence due to massive bleeding, so prompt and accurate diagnosis was definitely life-saving. Appropriate therapy or surgical intervention could be arranged.

Modulatory effects of BPC 157 on vasomotor tone and the activation of Src-Caveolin-1-endothelial nitric oxide synthase pathway.

BPC 157-activated endothelial nitric oxide synthase (eNOS) is associated with tissue repair and angiogenesis as reported in previous studies. However, how BPC 157 regulates the vasomotor tone and intracellular Src-Caveolin-1 (Cav-1)-eNOS signaling is not yet clear. The present study demonstrated a concentration-dependent vasodilation effect of BPC 157 in isolated rat aorta. Attenuation of this vasodilation effect in the absence of endothelium suggested an endothelium-dependent vasodilation effect of BPC 157. Although slightly increased vasorelaxation in aorta without endothelium was noticed at high concentration of BPC 157, there was no direct relaxation effect on three-dimensional model made of vascular smooth muscle cells. The vasodilation effect of BPC 157 was nitric oxide mediated because the addition of L-NAME or hemoglobin inhibited the vasodilation of aorta. Nitric oxide generation was induced by BPC 157 as detected by intracellular DFA-FM DA labeling which was capable of promoting the migration of vascular endothelial cells. BPC 157 enhanced the phosphorylation of Src, Cav-1 and eNOS which was abolished by pretreatment with Src inhibitor, confirming the upstream role of Src in this signal pathway. Activation of eNOS required the released binding with Cav-1 in advance. Co-immunoprecipitation analysis revealed that BPC 157 could reduce the binding between Cav-1 and eNOS. Together, the present study demonstrates that BPC 157 can modulate the vasomotor tone of an isolated aorta in a concentration- and nitric oxide-dependent manner. BPC 157 can induce nitric oxide generation likely through the activation of Src-Cav-1-eNOS pathway.

Laparoscopic metroplasty: reconstructive surgery for unicornuate uterus with noncommunicating, functional uterine horn.

OBJECTIVE: To demonstrate laparoscopic surgery for a patient with unicornuate uterus and a large hematometra in the noncommunicating uterine horn. DESIGN: Narrated video featuring the diagnostic tests and surgical management. SETTING: Academic tertiary hospital. PATIENT(S): A 13-year-old woman, gravida 0 with menarche at 9 years old, had severe dysmenorrhea during her recent menstrual cycles. The results of transrectal three-dimensional sonography, hysteroscopy, and magnetic resonance imaging (MRI) were consistent for a uterine didelphys composed of a right unicornuate uterus and a left hemiuterus with hematometra and no connection to the cervix. Left adnexal endometrioma and ipsilateral renal agenesis were also noted. INTERVENTION(S): Laparoscopic adhesiolysis and enucleation of the left ovarian endometrioma were first performed. Then, implementing the concepts of Strassman unification method, a horizontal incision was made on the medial side of each hemicorpus, starting from the left rudimentary horn and ending at the fundal area of the right hemiuterus. The incision was carried deep enough to reach the endometrium. The opposing, reverted myometrium was then reapproximated from the lower end of the uterus to the upper fundal part in two layers, using absorbable bidirectional monofilament barbed suture. The outer serosal layer was closed with 1-0 Monocryl via a running continuous suture. On postoperative day 2, the patient was discharged uneventfully. MAIN OUTCOME MEASURE(S): Symptomatic relief and restoration of normal and functional anatomy. RESULT(S): The patient has regular menstrual cycles with no recurrence of dysmenorrhea or ovarian endometrioma. At a 2-year postoperative follow-up evaluation, hysteroscopic examination revealed a single uterine cavity with a small fundal septum. The MRI scans showed an anteverted, symmetrical uterus. CONCLUSION(S): In comparison with the widely applied hemihysterectomy, reconstructive laparoscopic metroplasty not only effectively achieves symptomatic relief but also offers better uterine symmetry and a larger intrauterine cavity via unification of the uterus.

The anti-angiogenic effect of tryptanthrin is mediated by the inhibition of apelin promoter activity and shortened mRNA half-life in human vascular endothelial cells.

BACKGROUND: Anti-angiogenesis is an important strategy of psoriasis treatment, but the side effects of systemic agents remain difficult to overcome. Topical use of indigo naturalis ointment has been proved to improve the skin lesion of psoriasis effectively and safely and one of its major components, tryptanthrin, has been demonstrated to have anti-angiogenic effect. Apelin, which has been reported to act as an angiogenic factor that could stimulate the proliferation and migration of vascular endothelial cells and proved to be elevated in psoriasis patients, is a potential target of anti-angiogenic therapy. PURPOSE: We aim to find out if tryptanthrin works on the apelin pathway and study its anti-angiogenic mechanism. STUDY DESIGN: Human umbilical vein endothelial cells (HUVECs) were used as the in vitro model. METHODS: The effect of tryptanthrin on the expression of apelin and its receptor, APJ, was examined. The mRNA stability, promoter activity, and bioactivity of apelin, were also investigated. Migration and tube formation assay were used to evaluate the relationship between tryptanthrin and apelin. PD98059 and wortmannin were used to study the role of ERK1/2 MAPK and PI3K in apelin signaling pathway. RESULTS: We demonstrated that tryptanthrin could inhibit the expression of apelin, attenuated the stability of apelin mRNA, and significantly inhibited the apelin promoter activity. The addition of apelin-13 restored the suppression of tube formation and migration by tryptanthrin. Both PD98059 and wortmannin could down-regulate the apelin mRNA expression suggesting the important signaling role of ERK1/2 MAPK and PI3K in the gene expression of apelin. CONCLUSION: The anti-angiogenic effect of tryptanthrin was mediated by down-regulating apelin gene expression through suppression of promoter activity and decrease of mRNA stability in human vascular endothelial cells.

Interferon α-inducible protein 27 is an oncogene and highly expressed in cholangiocarcinoma patients with poor survival.

OBJECTIVE: Cholangiocarcinoma (CCA) is a devastating disease. Interferon α-inducible protein 27 (IFI27), originally known to involve in innate immunity, is later found to intervene in cell proliferation, leading to inventive studies regarding the role of IFI27 in cancer treatment. We aimed to investigate the role of IFI27 in CCA. MATERIALS AND METHODS: Cell proliferation, migration, and invasion assays, Western blot, gene transfection and knockdown, immunofluorescent and immunohistochemical stains, and xenograft animal model were applied. RESULTS: IFI27 knockdown in CCA cells induced cell cycle arrest in S phase, resulting in lower cell proliferative rate in vitro and in vivo. IFI27 knockdown attenuated CCA cell migration and invasion through inhibition of epithelial-mesenchymal transition, which was supported by increased E-cadherin and decreased N-cadherin and fibronectin. Filamentous actin level was also reduced. IFI27 knockdown further repressed expression and secretion of vascular endothelial growth factor (VEGF-A), a strong stimulator of angiogenesis, through downregulation of c-jun and c-fos, which was supported in vitro by the finding that human vascular endothelial cells grew more slowly in conditioned medium of IFI27 knockdown on CCA cells and in vivo by the lower erythropoietin concentration found in the xenografted tumors derived from IFI27 knockdown on CCA cells. In addition, anti-VEGF-A antibody treatment was able to repress CCA cell growth. To the contrary, IFI27 overexpression could increase CCA cell proliferation, migration, and invasion. Clinically, higher IFI27 expression was linked to inferior overall survival of CCA patients. CONCLUSION: Our data strongly suggest that IFI27 could be deemed as a potential target for CCA treatment.

Presurgical Identification of Uterine Smooth Muscle Malignancies through the Characteristic FDG Uptake Pattern on PET Scans.

The unidentified presence of uterine smooth muscle malignancies poses a tremendous risk in women planning surgery for presumed benign leiomyomas. We sought to investigate whether preoperative FDG PET may be useful to identify leiomyosarcomas (LMS) and smooth muscle tumors of uncertain malignant potential (STUMP). Methods. We investigated patients with rapidly growing uterine masses which were suspected of being malignant on ultrasound or MRI. Among the 21 patients who underwent FDG PET, we identified 7 LMS, 1 STUMP, and 13 leiomyomas. PET-derived parameters and FDG uptake patterns were analyzed retrospectively. Results. The SUVmax values of LMS/STUMP (range: 3.7-11.8) were significantly higher than those observed in leiomyomas (range: 2.0-9.4; P=0.003) despite a significant overlap. The metabolic tumor/necrosis ratio was significantly higher in LMS/STUMP than in leiomyomas (P < 0.001), with no significant intergroup overlaps. All LMS/STUMP revealed a characteristic pattern of FDG uptake, identifying a specific "hollow ball" sign (corresponding to areas of coagulative tumor necrosis). In contrast, this sign was invariably absent in patients with leiomyomas. Conclusion. The characteristic FDG uptake pattern instead of SUV on PET images allows identifying LMS/STUMP in patients with rapidly growing uterine masses, avoiding the deleterious consequences of regular surgery for presumed benign leiomyomas.

Persistent stress urinary incontinence during pregnancy and one year after delivery; its prevalence, risk factors and impact on quality of life in Taiwanese women: An observational cohort study.

OBJECTIVE: The study was to investigate the prevalence and risk factors of stress urinary incontinence (SUI) and its impact on the quality of life during pregnancy and 12 months after delivery. MATERIALS AND METHODS: 866 women delivering their newborns at a tertiary hospital were recruited. All women were asked to complete several questionnaires including demographic and obstetric data, Short Form 12 health survey (SF-12), Urogenital Distress Inventory Short Form (UDI-6), and Incontinence Impact Questionnaire Short Form (IIQ-7). All women were interviewed via telephone to answer the same questionnaires at 12 months postpartum. RESULTS: There were 446 (51.5%) self-reported SUI women during pregnancy. Out of 560 women delivered vaginally, 70 (12.5%) had SUI at 12 months postpartum; in 306 women undergoing Cesarean delivery, 22 (7.2%) experienced SUI 12 months after delivery. Risk factors of SUI during pregnancy included body weight and body mass index at first visit. At 12 months postpartum, parity stood out as the risk factor of persistent SUI in vaginal delivery group, but no significant risk factor was found in Cesarean group. Women with SUI during pregnancy featured worse mental component summary (MCS) score of SF-12, compared to women without SUI. At 12 months postpartum, women with persistent SUI in vaginal delivery group had higher mean UDI-6 and IIQ-7 scores than those without SUI. CONCLUSION: Persistent SUI is more prevalent in the vaginal delivery group than Cesarean group. Both SUI during pregnancy and after childbirth have negative impact on the quality of life in women undergoing vaginal delivery.

Novel GM-CSF-based vaccines: One small step in GM-CSF gene optimization, one giant leap for human vaccines.

Granulocyte macrophage-colony stimulating factor (GM-CSF) is a potent immunomodulatory cytokine that is known to facilitate vaccine efficacy by promoting the development and prolongation of both humoral and cellular immunity. In the past years we have generated a novel codon-optimized GM-CSF gene as an adjuvant. The codon-optimized GM-CSF gene significantly increased protein expression levels in all cells tested and helped in generating a strong immune responses against HIV-1 Gag and HPV-associated cancer. Here, we review the literature dealing with the adjuvant activity of GM-CSF both in animal models and clinical trials. We anticipate that the codon-optimized GM-CSF gene offers a practical molecular strategy for potentiating immune responses to tumor cell-based vaccinations as well as other immunotherapeutic strategies.

Voiding dysfunction in women following cesarean delivery.

OBJECTIVE: This study was conducted to investigate the prevalence of postpartum voiding difficulty (PVD) in women after cesarean delivery that required urethral catheterization, and to illustrate its relationship with various relevant obstetric factors. MATERIAL AND METHODS: For this observational study, 489 pregnant women who had cesarean delivery at ≥ 36 gestational weeks were recruited in a tertiary hospital. Urethral catheterization was implemented in women who could not void spontaneously after cesarean delivery. Patient characteristics, obstetric parameters, and incidences of obstructive voiding symptoms at 3 months postpartum were compared between women who had PVD and no PVD. RESULTS: Fifty-six cesarean deliveries (11.5%) resulted in PVD. Maternal age > 35 years, emergency cesarean delivery, operation time > 60 minutes, and postoperative analgesia were significantly different between women with and without PVD. Logistic regression demonstrated that emergency cesarean delivery (odds ratio = 5.031, p < 0.001), operation time > 60 minutes (odds ratio = 2.918, p = 0.002), and postoperative analgesia (odds ratio = 7.610, p = 0.007) were independent risk factors of PVD. Nonetheless, all women had resolution of PVD by the time of hospital dismissal. At 3-month postoperative follow-up, three women (5.4%) had symptoms of straining and/or incomplete emptying. CONCLUSION: Our results showed that emergency cesarean delivery, prolonged operation time and postoperative analgesia are the main contributing factors of PVD after cesarean delivery. If urinary retention can be detected in time, transient PVD is not detrimental to urinary function and does not subsequently lead to voiding problems.