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We have prepared various [([Ge.sub.1-y][Pb.sub.y]).sub.1-x][Mn.sup.x] Te thin films by an ionized cluster beam method on Ba[F.sub.2] (111) substrates in order to study the dependences of electrical and magnetic properties on Pb content. Carrier concentration can be controlled from [10.sup.18] [cm.sup.-3] (y = 0.69) to [10.sup.21] [cm.sup.-3] (y = 0) by Pb content in the films with Mn content x around 0.1. Direct magnetization and magnetotransport measurements were performed and the characteristics of anomalous Hall effect agreed well with the magnetization. The Curie temperature of [([Ge.sub.1-y][Pb.sub.y]).sub.1-x][Mn.sub.x] Te films decreased with increasing Pb content and ferromagnetic behavior was not observed in magnetotransport measurement at 9 K for the films above y : 0.57. An increase of Mn content in [([Ge.sub.1-y][Pb.sub.y].sub.1-x][Mn.sub.x] Te films with Pb content y around 0.47 has also been tried. The Curie temperature successfully increased with increasing Mn content till x = 0.22. Index Terms--Carrier-induced ferromagnetism, chalcogenide, magnetic semiconductors, IV-VI semiconductor.

Introduction: We previously showed the trend of antimicrobial use (AMU) for Clostridioides (Clostridium) difficile infection (CDI) using sales data. However, the details of the prescribing medical institutions and regional characteristics are unknown. Therefore, the purpose of this study was to clarify the details of the medical institutions where antibiotics for CDI were prescribed, and evaluate the AMU for CDI and the regional characteristics., Methods: Antibiotics for CDI, including oral vancomycin (VCM), oral metronidazole (MNZ), and intravenous (IV) MNZ, were collected from the National Database of Health Insurance Claims and Specific Health Checkups (NDB) between 2013 and 2016. The PID (patients/1000 inhabitants/day) was used as an evaluation index for AMU. The PID was calculated using the claim types: inpatient, outpatient, dental, and pharmacy. The PID of each prefecture was calculated for inpatient claims in 2016., Results: The AMU of oral VCM and IV MNZ were observed mainly in the inpatient claims. For oral MNZ, the total AMU in the outpatient and pharmacy claims accounted for approximately 80% per year throughout the study period. For inpatient claims of each prefecture in 2016, the PID of the antibiotics used for CDIs was approximately 3.5 times the difference between the highest and lowest prefectures., Conclusions: The AMU for CDI that takes into account the purpose of use was clarified by using the information of the prescribed medical institutions that were included in the NDB. Oral MNZ was used frequently in outpatients, and attention should be paid to the acquisition of resistance., (Copyright © 2021. Published by Elsevier Ltd.)

Hexagonal tungsten oxide (h-WO 3 ) membrane is a novel candidate for dehydration of acetic acid (CH 3 COOH)/water mixtures owing to its molecular sieving property and acidic resistance. Meanwhile, c-plane orientation is an important factor for h-WO 3 membranes because the pores of h-WO 3 run along its c-axis. However, so far, high c-plane orientation has not been successful on tubular substrates. Here, the effect of synthesis conditions of h-WO 3 membranes on tubular substrates against c-plane orientation and CH 3 COOH/water separation performance are investigated. The h-WO 3 membranes were prepared by hydrothermal synthesis from a precursor sol containing various amounts of sodium tungstate (Na 2 WO 4 ) in the presence of tubular substrates with seeds embedded on their outside surface. The seeding method and the amount of Na 2 WO 4 in the precursor sol significantly affected both crystal orientation and densification of the membrane. A precursor sol with appropriate amounts of Na 2 WO 4 was essential to simultaneously satisfy high c-plane orientation and densification of the membrane while excess Na 2 WO 4 drastically decreased the degree of c-plane orientation. A highly c-plane oriented h-WO 3 membrane was successfully obtained under the optimized condition, which exhibited a maximum separation factor of 40.0 and a water permeance of 1.53 × 10 -7 mol·m -2 ·s -1 ·Pa -1 in a 90:10 wt % CH 3 COOH/water mixture. The water permeance approximately doubled compared to the previous report, possibly owing to the significantly higher degree of c-plane orientation. Furthermore, it was found that its separation ability can be maintained while stored in 90:10 wt % CH 3 COOH/water mixture with pH < 0 for more than 500 h.

Background: We aimed to retrospectively review data of pregnant women with the α-fibrinogen Thr331Ala polymorphism; evaluate the relationship between this polymorphism and spontaneous abortion (SA), fetal growth restriction (FGR), and intrauterine fetal death (IUFD); and assess the effects of aspirin and/or heparin. Materials and methods: We examined the outcomes of 29 pregnancies (nine women) in women with the α-fibrinogen Thr331Ala polymorphism. Of these, 16 were untreated, whereas 13 were treated with heparin and/or aspirin. Results: The live birth rate was significantly higher in the treated group than in the nontreated group (69.2 versus 6.2%; p = .0004). In addition, the prophylactic use of a low dose of aspirin and/or heparin during early pregnancy in women with Thr331Ala may be an effective method for reducing fetal loss in these patients. Conclusions: This polymorphism interacts with pregnancy to result in poor obstetrical outcomes, but these effects can be mitigated with medical intervention. This study is the first to report outcomes of pregnancies complicated by the Thr331Ala polymorphism, which we believe may cause thrombophilia, SA, and IUFD. This study highlights the need for further research on this polymorphism in pregnancy.

Objective: This study aimed to evaluate whether the Edinburgh Postnatal Depression Scale (EPDS) score predicts the occurrence of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) after delivery., Materials and Methods: The women in this study were registered at 35-36 weeks of pregnancy at Mie University Hospital from 2013 to 2015. We prospectively divided the puerperants into those with an EPDS score ≥9 (the high-EPDS group) and those with an EPDS score <9 (the low-EPDS group) at 1 month postpartum. We compared the incidence rate of severe PMS and PMDD between both groups at 1 year after delivery., Results: Of 200 registered cases, 178 (89.0%) did not experience severe PMS or PMDD before pregnancy. Among them, 21 were in the high-EPDS group, and 89 in the low-EPDS group. Four of the 21 women (19.0%) in the high-EPDS group and five of the 89 (5.6%) in the low-EPDS group had severe PMS or PMDD at 1 year after delivery. The incidence rate of severe PMS or PMDD in the high-EPDS group was higher than that in the low-EPDS group (p = 0.07)., Conclusions: The novel finding of this study is that the EPDS may predict the occurrence of severe PMS/PMDD after delivery. The EPDS will contribute to the early detection of these diseases and to improving the quality of life of the patients by allowing treatment initiation at an early stage., Competing Interests: Declaration of competing interest Erina Takayama, Takashi Sugiyama, Tadaharu Okano received research funding from Japan Society for the Promotion of Science (JSPS) KAKENHI, Japan Grant Number JP23591702. Hiroaki Tanaka, Yuki Kamimoto, Eiji Kondo and Tomoaki Ikeda report no potential conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

Purpose: The aim of this study is to evaluate the safety of clinical usage of tadalafil in women with preeclampsia. Materials and methods: Maternal, fetal, and neonatal adverse events were closely examined in eight preeclampsia patients receiving tadalafil treatment. Results: There were no maternal adverse events associated with 10 mg/day of tadalafil. Even at 20 mg/day, only grade 1 headaches in two cases and grade 1 palpitation in one case were observed, which resolved spontaneously within 3 days. At a dose of 40 mg/day, there was only one case of grade 1 headache. All these adverse events were grade 1 and spontaneously resolved within 3 days. There were no fetal adverse events. All observed neonatal adverse events were thought to be caused by prematurity and not related to tadalafil. Conclusion: This study shows that tadalafil treatment for preeclampsia is deemed sufficiently tolerable. Although there was a dose-dependent increase in maternal adverse events, all the adverse events were mild and deemed to be safe for the mother and fetus at all dosages.

Aim: To determine whether the area of the foveal avascular zone (FAZ), as a morphological indicator of the microcirculation of the perifoveal capillary network, changes in the carbohydrate metabolism disorders during pregnancy (the gestational age of patients with gestational diabetes mellitus (GDM) and preexisting diabetes (PexD))., Methods: Ten normal individuals and 41 eyes of 41 patients, 28 with GDM and 13 with PexD, were studied. A 3 × 3 mm area of the FAZ of the superficial capillary plexus layer (SCP) and the deep capillary plexus layer (DCP) was determined by optical coherence tomography angiography (OCTA; RS-3000 Advance, NIDEK). The significance of the correlation between the size of the FAZ and the weeks of pregnancy was determined., Results: The area of the FAZ of the SCP was 0.38 ± 0.11 mm 2 (normal eyes), 0.41 ± 0.16 mm 2 (GDM), and 0.43 ± 0.10 mm 2 (PexD). The area of the FAZ of the DCP was 0.78 ± 0.23 mm 2 (normal eyes), 0.69 ± 0.16 mm 2 (GDM), and 0.79 ± 0.25 mm 2 (PexD). No significant difference in the FAZ sizes was observed between the groups. The average number of weeks of pregnancy was 24.1 ± 8.2 weeks in the eyes with GDM and 23.3 ± 11.4 weeks in the eyes with PexD ( P > 0.05). Significant correlations were found between the size of the FAZ of the SCP and the number of weeks ( r  = 0.37, P =0.04 for GDM, and r  = 0.49, P =0.04 for PexD, Spearman's rank-order correlation coefficient)., Conclusions: For GDM and PexD under established glycemic control, the area of the FAZ is not affected, but vascular changes occurred at the early phase of pregnancy., Competing Interests: Masahiko Sugimoto has received financial support from Alcon Pharma (class III) and Bayer (class III) and lecture fee from Alcon pharma (class II), Kowa Pharma (class II), Senjyu Pharma (class II), Daiichi Yakuhin Sangyo (class II), Bayer (class II), and Wakamoto Pharma (class II)., (Copyright © 2019 Masahiko Sugimoto et al.)

MOR zeolite is an effective adsorbent for separating organic molecules from various solutions owing to its large windows of 0)65 × 0)70 nm and its relatively high silica-alumina ratio which provides higher hydrophobicity. Fine powdery MOR zeolite is desirable for adsorption of organic molecules considering its larger surface area; however, fine particles are difficult to remove from solutions after treatment. Intensification of magnetic susceptibility through combination with magnetic particles ensure quick and easy removal of fine adsorbents by magnetic force. Meanwhile, seed assisted method is a powerful technique to direct and accelerate zeolite synthesis by adding seed crystals into the precursor sol prior to hydrothermal synthesis. In this work, we selected magnetite as the magnetic particle and propose the hydrothermal synthesis of MOR zeolite/magnetite composite via seed assisted method for the first time. MOR zeolite/magnetite composite with high MOR zeolite crystallinity was obtained by synthesizing for only 6 hours at 463 K when adding seed crystals, while no sign of crystallization was observed even after 24 hours in their absence. In addition, pre-milling of seed crystals together with magnetite was found to be effective to incorporate magnetite into MOR zeolite during crystallization and to decrease the primary crystal size of the crystallized MOR zeolite.

Purpose: Fetal growth restriction (FGR) is a concerning health issue. However, studies on FGR management are limited due to its rarity. We aimed to evaluate the efficacy of the contraction stress test (CST) for FGR management. Materials and methods: A case-control retrospective study design. Our institute innovated CST in FGR management in 2017. We included women in their 33rd-40th week of pregnancy with a diagnosis of FGR and retrospectively divided them into groups: the CST group (FGR management with CST) and no CST group (FGR management without CST) before and after CST development. Neonatal outcome, pH, and pO 2 of umbilical artery (UA) were compared between the two groups. Results: No significant differences in the rate of birth weight, Apgar score <7 (5 minutes), neonatal death, hospitalization to newborn childhood intensive care unit (NICU), and UA pH were found between groups. Average UA pH was 7.29 ± 0.05 and 7.29 ± 0.04 in the CST and no CST groups, respectively ( p  = .864). Average UA pO 2 values were 21.1 ± 8.6 and 15.7 ± 5.0 mmHg in the CST and no CST groups, respectively ( p  = .016), showing significant differences. Conclusions: Neonatal outcomes and UA pH were slightly different between the groups managed with and without CST. However, UA pO 2 values significantly differed between the groups. For FGR management, the use of a CST may allow for early intervention before fetal acidemia and acidosis. For establishing the effects of a CST for FGR management, analysis including several cases and investigation of long-term outcomes of newborn infants is necessary.

Purpose: We recently demonstrated the efficacy of tadalafil treatment for fetal growth restriction (FGR). This study aimed to evaluate the utility of serum placental growth factor (PlGF) level for predicting the efficacy of tadalafil for the treatment of FGR. Materials and methods: The correlations between serum level of PlGF and fetal growth velocity were retrospectively assessed in nine pregnant women receiving tadalafil for FGR before 30 weeks' gestation. Results: Median gestational age was 26 weeks (range 26-28 weeks), and median deviation of estimated fetal weight from standard weight was -2.1 standard deviations (SD) (-2.2 to -1.9 SD) at the beginning of tadalafil treatment. The median serum PlGF level was 227 pg/ml (40.2-427.0 pg/ml) before tadalafil treatment and 278 pg/ml (66.2-729.5 pg/ml) more than 2 weeks after initiation of tadalafil treatment (median gestational week at measurement of PlGF after treatment, 33 weeks [28-33 weeks]). The median fetal growth velocity from enrollment to birth was 17.5 g/day (12.1-20.3 g/day). Maternal serum PlGF levels were increased after tadalafil treatment in all nine cases (median increase in PlGF, 73.1 pg/ml [26.0-281.5 pg/ml]). Notably, maternal serum PlGF level before tadalafil treatment significantly correlated with fetal growth velocity ( R 2  = 0.63, p  < .01). Conclusions: Tadalafil treatment may increase maternal serum PlGF levels. Our results suggest that maternal serum PlGF levels can be used as a predictor of the efficacy of tadalafil treatment for FGR.

The aim of this study was to determine the action of molecules in carbohydrate metabolism disorders during pregnancy. The concentration of different types of cytokines and vascular endothelial growth factor (VEGF) in the plasma were measured in 4 groups of women: Group I, normal pregnancy (n = 10); Group II, patients with gestational DM (n = 12); Group III, pregnant patients with preexisting DM (n = 16); and Group IV, diabetic non-pregnant women (n = 22). The plasma VEGF concentration was significantly higher in the women in Group IV than in other groups (P <0.01). The concentration of the soluble form of the VEGF receptor-1 (sVEGFR-1) was significantly higher in Group I than in other groups (P <0.01). The concentration of soluble form of the VEGF receptor-2 (sVEGFR-2) was significantly lower in Groups I than in other groups (P <0.05). The concentrations of monocyte chemotactic protein-1 (MCP-1) and eotaxin were significantly lower in Group I than in Groups III and IV. The levels of interleukin (IL)-8, IL-6, and tumor necrosis factor-α (TNF-α) were significantly higher in Group I than in Group IV. Both the VEGF-related molecules and the Inflammatory cytokines are altered in pregnant women with the carbohydrate metabolism disorders., Competing Interests: The authors have declared that no competing interests exist.

Background: The aim of the present study was to evaluate tadalafil for the treatment of fetal growth restriction (FGR) and the cardiac function in pregnant women without cardiovascular disease who used tadalafil for this reason., Materials and Methods: We examined nine pregnant women without cardiovascular disease who were using tadalafil to treat FGR. Maternal heart rate, systolic blood pressure (BP), and echocardiographic findings were assessed before and after tadalafil use., Results: Diastolic BP was lower after compared to that before using tadalafil, but the difference was not significant. Echocardiographic findings were not significantly different before and after tadalafil use., Conclusions: Tadalafil did not adversely affect pregnant women without cardiovascular disease and was considered acceptable for use since it did not affect the mother's cardiac function.

Purpose: Multimodal analgesia has become an important concept in current pain management following total knee arthroplasty (TKA). However, controversy remains over what is the most accepted combination. In this study, the additional benefits of local infiltration of analgesia to femoral nerve block were evaluated., Methods: Forty patients were randomly allocated into a combined local infiltration of analgesia and femoral nerve block or femoral nerve block alone group. In the former, analgesic drugs consisting of ropivacaine and dexamethasone were injected into the peri-articular tissues, while the same amount of saline was injected into the femoral nerve block group. The primary outcome measure was the total amount of fentanyl consumption by the patient-controlled analgesia pump during the 48-h post-operative period., Results: A combination of local infiltration of analgesia and femoral nerve block had less total fentanyl consumption and a larger knee ROM at post-operative day 2 than femoral nerve block alone (p < 0.05). C-reactive protein levels in the combined treatment group were significantly lower than the femoral nerve block group at post-operative day 3 (p < 0.01). There was no difference between the two groups, post-operatively, on the visual analogue scale for pain at rest or while walking, quadriceps strength, timed up and go test, circumference of thigh, Knee Society Score, and Western Ontario and McMaster Universities Osteoarthritis Index., Conclusion: The addition of local infiltration of analgesia to femoral nerve block promoted post-operative pain relief and the recovery of knee ROM in the early post-operative period. This combination is an effective method for post-operative pain management after TKA., Level of Evidence: Randomized controlled trial, Level I.

We have demonstrated that tadalafil facilitates fetal growth in mice with L-NG-nitroarginine methyl ester (L-NAME)-induced preeclampsia (PE) with fetal growth restriction (FGR). Tadalafil is a selective phosphodiesterase 5 inhibitor that dilates the maternal blood sinuses in the placenta, thereby facilitating the growth of the fetus. The purpose of this study was to investigate the effects of tadalafil treatment for PE and FGR on the developing brain in FGR offspring using an L-NAME-induced mouse model of PE with FGR. A control group of dams received carboxymethylcellulose (CMC). L-NAME-treated groups received L-NAME dissolved in CMC from 11 days post coitum (d.p.c.). The L-NAME-treated dams were divided into two subgroups 14 d.p.c. One subgroup continued to receive L-NAME. The other subgroup received L-NAME with tadalafil suspended in CMC. Tadalafil treatment for PE with FGR reduced the expression of hypoxia-inducible factor-2α in the placenta and in the brain of the FGR fetus. Moreover, tadalafil treatment in utero shows improved synaptogenesis and myelination in FGR offspring on postnatal day 15 (P15) and P30. These results suggest that tadalafil treatment for PE with FGR not only facilitates fetal growth, but also has neuroprotective effects on the developing brain of FGR offspring through modulating prenatal hypoxic conditions.

Introduction: There is no proven therapy to reverse or ameliorate fetal growth restriction (FGR). Sildenafil, a selective phosphodiesterase 5 (PDE5) inhibitor, has been reported to potentially play a therapeutic role in FGR, but this has not been established. Tadalafil is also a selective PDE5 inhibitor. We have demonstrated the efficacy of tadalafil against FGR along with short-term outcomes and the feasibility of tadalafil treatment. Based on the hypothesis that tadalafil will safely increase the likelihood of increased fetal growth in FGR, we designed this phase II study to prospectively evaluate the efficacy and safety of tadalafil against FGR., Methods and Analysis: This study is a multicentre, randomised controlled phase II trial. A total of 140 fetuses with FGR will be enrolled from medical centres in Japan. Fetuses will be randomised to receive either the conventional management for FGR or a once-daily treatment with 20 mg of tadalafil along with the conventional management until delivery. The primary endpoint is fetal growth velocity from the first day of the protocol-defined treatment to birth (g/day). To minimise bias in terms of fetal baseline conditions and timing of delivery, a fetal indication for delivery was established in this study. The investigator will evaluate fetal baseline conditions at enrolment and will decide the timing of delivery based on this fetal indication. Infants will be followed up for development until 1.5 years of age., Ethics and Dissemination: This study was approved by the Institutional Review Board of Mie University Hospital and each participating institution. Our findings will be widely disseminated through peer-reviewed publications., Trial Registration Number: UMIN000023778., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We investigated the efficacy and mechanisms of tadalafil, a selective phosphodiesterase 5 inhibitor, in treating preeclampsia (PE) with fetal growth restriction (FGR) using L-NG-nitroarginine methyl ester (L-NAME)-induced PE with FGR in pregnant mice as our experimental model., Methods: C57BL/6 mice were divided into 2 groups 11 days postcoitum (d.p.c.). A control group of dams (C dam) received 0.5% carboxymethylcellulose (CMC). A L-NAME-treated group received 1 mg/ml L-NAME dissolved in CMC. The L-NAME-treated dams were divided into 2 subgroups 13 d.p.c. One subgroup continued to receive L-NAME (L dams). The other subgroup received L-NAME with 0.08 mg/ml tadalafil suspended in CMC (TL dams). Maternal systolic blood pressure (SBP) and proteinuria were assessed 16 d.p.c. Fetal weight was recorded, and placentas and maternal kidneys were collected 17 d.p.c., Results: Maternal SBP, proteinuria, and fetal weight were improved for TL dams compared to L dams. The placental concentration of placental growth factor (PlGF) was higher for TL dams than for the C and L dams. The placental maternal blood sinuses of L dams were narrower than those of C dams, but those of TL dams improved to a similar width as C dams. Glomerular oxidative stress was ameliorated in TL dams compared to L dams., Conclusions: Tadalafil dilates the placental maternal blood sinuses, which leads to increase PlGF production, and contributes to facilitate fetal growth and improve maternal SBP. Moreover, tadalafil ameliorates glomerular damage by reducing oxidative stress. These results suggest that tadalafil is a candidate for treatment of PE with FGR., (© American Journal of Hypertension, Ltd 2017. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Thrombotic thrombocytopenic purpura (TTP) frequently develops in patients with connective tissue diseases (CTDs). ADAMTS13 and von Willebrand factor (VWF) are closely related to the onset of TTP. We investigated the roles of ADAMTS13 and VWF in thrombotic events of patients with CTD. ADAMTS13 activity and VWF and VWF propeptide (VWFpp) levels in CTD, primary antiphospholipid antibody syndrome (pAPS), and controls were measured to examine their relationship with thrombosis. ADAMTS13 activity levels were significantly low in the patients with CTD but not in the patients with pAPS. No significant difference in the ADAMTS13 activity levels among the various CTD subgroups was found. The levels of VWF and VWFpp were significantly elevated in the patients with pAPS and CTD compared with that of control groups. Eleven patients with CTD developed TTP, and their ADAMTS13 activity levels were significantly lower than patients having CTD without TTP. However, the ADAMTS13 activity levels showed no difference between the patients having CTD with and without thrombotic events. The VWF antigen levels were significantly high in the patients having CTD with TTP. There were no significant differences in the VWF levels of the patients having CTD with TTP and thrombosis. The VWFpp levels were significantly high in the patients having CTD with TTP and thrombosis. The VWF and VWFpp levels were significantly high in the patients with pAPS. Decreased ADAMTS13 activity and elevated VWF and VWFpp levels were observed in patients with CTD. These abnormalities in patients with CTD may represent the increased risk of thrombosis in CTD.

Aim: We designed a safety and dose-finding trial of tadalafil administered for fetal growth restriction (FGR)., Methods: Three cases were initially commenced on 10 mg/day and monitored for major adverse events. Should a major adverse event be observed in one or more of the three cases, an examination into its relation with tadalafil would be conducted by a safety evaluation committee. If one or more of these new cases exhibited the same adverse event, the trial would be stopped completely. If there were no harmful side-effects, the trial would be extended to three cases at 20 mg/day, and the protocol would continue as in the 10-mg/day dose. The 40-mg/day dosage was tried in six cases as the dosage was considered to be high., Results: The study population consisted of pregnant women with FGR. Maternal adverse events in all doses were recorded as least one grade 1 adverse events, as tadalafil was considered acceptable from the viewpoint of the mothers. However, a dose of 40 mg/day increased the number of grade 1 adverse events. The only fetal adverse event was a case of intrauterine fetal death related to the velamentous insertion of the umbilical cord. Neonatal adverse events showed no correlation to tadalafil dose, but were found more frequently in preterm births and, therefore, were correlated to infant prematurity., Conclusion: This safety and dose-finding trial showed that tadalafil had a favorable safety profile for pregnant women and fetuses with FGR., (© 2017 Japan Society of Obstetrics and Gynecology.)

Congenital thrombophilia which is characterized by deficiencies in proteins such as antithrombin (AT), protein C (PC) and protein S (PS), is a major cause of venous thromboembolism (VTE). A total of 130 patients with VTE were evaluated for congenital thrombophilia based on the activity of AT, PC, or PS. Fifteen VTE patients with congenital AT deficiency (11.5 %), 16 with congenital PC deficiency (12.3 %) and eight with congenital PS deficiency (6.2 %) were diagnosed using DNA analysis. The frequency of congenital AT deficiency was significantly higher in subjects with pregnancy-related and idiopathic VTE than in those with VTE due to other causes, and congenital PC and PS deficiency were frequently associated with idiopathic VTE. Among the groups examined, the plasma levels of AT were the lowest in subjects with pregnancy-related VTE. Although our findings may have been influenced by some unintentional bias, congenital thrombophilia is nevertheless a major cause of VTE in pregnant patients as well as in young or middle-aged patients without any underlying diseases.

Aim: The aim of this retrospective study was to assess tadalafil treatment in pregnant women with fetal growth restriction (FGR) in terms of maternal and perinatal outcomes., Methods: We retrospectively analyzed 11 Japanese singleton pregnant women with FGR who received tadalafil along with conventional management for FGR at Mie University Hospital from July 2015 to February 2016 (tadalafil group). These women were matched for maternal age, parity, gestational age, and estimated fetal weight at enrollment with 14 singleton pregnant women who received only the conventional management for FGR in 2014 (conventional management group). The conventional management for FGR was performed according to guidelines for obstetric practice in Japan., Results: Both birthweight and fetal growth velocity from enrollment to birth were significantly higher in the tadalafil group than in the conventional management group. The cesarean delivery rate was approximately twofold higher in the conventional management group than in the tadalafil group. Importantly, cesarean section due to non-reassuring fetal status was performed in seven pregnant women in the conventional management group (58.3%) but in none in the tadalafil group (P < 0.05, chi-squared test)., Conclusions: Tadalafil may improve perinatal outcome in FGR by modulating fetal growth through maintenance or improvement of fetal well-being., (© 2016 Japan Society of Obstetrics and Gynecology.)

We analyzed a cohort of 36 females with pregnancy loss. In addition to 11 patients with antiphospholipid antibody syndrome and 2 patients with congenital antithrombin (AT) or protein C deficiency, we identified 5 patients with low fibrinogen levels (median 110 mg/dL) prior to 10 weeks of gestation. Four of these 5 patients underwent a fibrinogen gene analysis, and all 4 were found to be heterozygotes for the α-fibrinogen (FGA) Thr321Ala polymorphism. One female without hypofibrinogenemia with a history of 8 pregnancy losses was found to be homozygous for the same polymorphism, and she also showed hypercoagulability without thrombosis. In conclusion, there was a relatively high frequency of pregnancy loss in the setting of hypofibrinogenemia and/or the FGA Thr312Ala polymorphism, and this may be an important risk factor for pregnancy loss and a hypercoagulable state in later pregnancy., (© The Author(s) 2015.)

Background: Severe early-onset fetal growth restriction occurs in 0.4 % of all pregnancies, and the prognoses of these patients are dismal. Severely growth-restricted fetuses (far below 500 g) are thought to be nonviable. Since there have not been effective treatments for such fetal patients, obstetricians have simply tried to identify the optimal timing for their delivery. There are a few reports suggesting that the phosphodiesterase type 5 inhibitor sildenafil has some limited beneficial effects on fetal growth, but there are no such reports on tadalafil, another derivative phosphodiesterase type 5 inhibitor which has a much longer half-life than sildenafil. Here we present a case in which the administration of tadalafil to the mother revived the arrested growth and severe oligohydramnios of the very prematurely growth-restricted fetus., Case Presentation: We describe a case of early-onset fetal growth restriction with oligohydramnios in a 41-year-old primigravida Japanese woman who was treated with tadalafil (20-mg tablet daily) from 22 weeks' gestational age. Ten days after the initiation of the tadalafil therapy, the amniotic fluid level rose and the weight of the fetus began to increase. A 1024-g baby boy was delivered by cesarean at 32 weeks' gestation. The z-score for fetal head circumference had increased from -2.2 to -1.2, whereas the z-score of the femur legth was decreased to -4.3, indicating that tadalafil preferentially increased the blood flow to important organs., Conclusions: We achieved two positive results by administering tadalafil to the mother carrying a severely growth-restricted fetus with oligohydramnios. First, the z-scores of head circumference and abdominal circumference had at first declined but started to rise after the tadalafil administration. Second, the amniotic fluid, which was emptied before the tadalafil treatment, recovered to normal range with this treatment. Tadalafil administration to mothers could be a promising therapy to reverse severe fetal growth restriction and oligohydramnios.

Objective: Antiphospholipid syndrome (APS) is a well-known complication of habitual abortion and/or thrombosis and is frequently associated with autoimmune diseases., Methods: We retrospectively investigated the relationships between the presence of antiphospholipid antibodies (aPLs) and the incidence of thrombotic events (THEs) in 147 patients with various connective tissue diseases (CTD) suspected of having APS and 86 patients with idiopathic thrombocytopenic purpura (ITP). THEs were observed in 41 patients, including 14 cases of venous thrombosis, 21 cases of arterial thrombosis and eight cases of complications of pregnancy., Results: The prevalence of THE was significantly high in the systemic lupus erythematosus (SLE) patients compared with the other CTD patients and ITP patients. The frequency of lupus anticoagulant (LA), anticardiolipin antibodies (aCL)-β2-glycoprotein (GPI) complex IgG and aPL was significantly high in the SLE patients compared with the ITP patients. Subsequently, the rate of development of THE was significantly high in the patients with aPLs. In particular, the incidence of THE was significantly high in the SLE or ITP patients with LA, aCL-β2GPI IgG or aPL. The optimal cut-off values for LA, aCL IgG and aCL-β2GPI complex IgG for the risk of THEs were higher in the SLE patients in comparison to the values obtained when using the kit provided by the manufacturer., Conclusion: Although aPLs is frequently associated with SLE and is a causative factor for thrombosis, the optimal cut-off value for aPL for predicting the occurrence of THEs varies among different underlying diseases.

During normal pregnancy, the pro-coagulant activity is increased, while the anticoagulant activity is reduced, resulting in a prothrombotic environment that predisposes toward venous thromboembolism (VTE). VTE occurs frequently in pregnant women and is a leading cause of maternal morbidity and mortality. Hemostatic abnormalities were examined in 14 pregnant women with deep vein thrombosis (DVT). We studied five families with congenital antithrombin (AT) deficiency and two families with congenital protein C (PC) deficiency. One woman with PC deficiency showed protein S (PS) Tokushima. The AT activity levels were significantly lower at the onset of DVT in the pregnant women than during the stable state. The PS activity and antigen levels were also significantly lower at the onset of DVT. In the patients with congenital AT deficiency, AT activity was significantly lower in the stable state and decreased further at the onset of DVT. Although AT levels were normal before pregnancy, they subsequently decreased and in two cases the patients required the administration of AT after pregnancy. Gene analysis revealed one family with AT Budapest, one family with AT Toyama, and three families with AT Glasgow. Additionally, there was one family with PC Tochigi and one family with combined heterozygous PC deficiency and PS Tokushima. In conclusion, the deficiency of natural anticoagulants, especially AT, is an important cause of pregnancy-related VTE.

Purpose: It has been known for years that deep vein thrombi (DVT) start to develop during total joint arthroplasty. Previously, we reported effective prevention of venous stasis by transcutaneous electrical nerve stimulation (TENS). It is hypothesized that TENS might be a thromboprophylactic tool for the limb undergoing surgery. The purpose of this study is to clarify the clinical efficacy and safety of TENS in patients during total knee arthroplasty (TKA)., Methods: Ninety patients undergoing primary TKA were involved and randomly allocated to the TENS or control group. In the TENS group, electrical stimulation of the common fibular nerve, which produced a brisk dorsiflexion of the ankle, was performed for the operated leg during surgery. In the control group, no electrical stimulation was applied. Serum D-dimer and soluble fibrin monomer complex (SFMC) levels were measured before surgery, immediately after surgery, and post-operative day (POD) 1. Ultrasonography was performed on POD 1., Results: Immediately after surgery, D-dimer and SFMC levels of each group were significantly lower in the TENS group compared with control (p < 0.05). The incidence of DVT was 11 % (five cases) in the TENS group while 31 % (14 cases) in control (p = 0.02). There were no adverse effects related to TENS., Conclusions: TENS during TKA showed significant effects on preventing DVT. Sustaining muscle pump activation during surgery prevented not only venous stasis, but also hypercoagulability of blood. Intraoperative TENS is a safe and novel strategy against early post-operative thromboembolism, which is difficult to be completed through existing prophylaxis after total joint arthroplasty., Level of Evidence: Randomized controlled trial, Level I.