Shiho Nagayama

Uterine artery pseudoaneurysm: its occurrence after non-traumatic events, and possibility of “without embolization” strategy

OBJECTIVES Uterine artery pseudoaneurysm (UAP) has been considered to occur very rarely after traumatic delivery/abortion, and is usually detected after its rupture, yielding massive bleeding. Our hypothesis is: some UAP may be undetected without massive bleeding and may spontaneously resolve, and, thus, may not require transarterial embolization (TAE). We attempted: (1) to detect both ruptured and non-ruptured UAP, thereby characterizing candidates of spontaneously resolving UAP, and (2) to confirm that UAP is not rare and not always associated with traumatic events. STUDY DESIGN This was a retrospective observational study of 50 women with angiographically confirmed UAP and treated by TAE. Angiograms and medical charts were retrieved to examine the associations among symptoms, ultrasound findings, and extravasation. Gray-scale ultrasound was performed for all women after delivery or abortion as our routine practice. RESULTS UAP occurred in 3-6/1000 deliveries and 40% occurred after non-traumatic deliveries/abortion. While 36% had active vaginal bleeding at admission, 64% did not. While 100% of patients with current active bleeding showed extravasation from the pseudoaneurysmal sac, patients without it showed a varied incidence of extravasation depending on the bleeding pattern/history and ultrasound findings. Interestingly, all patients with current bleeding (-), bleeding history (+), and ultrasound-discernable-intrauterine low echoic mass (-) were devoid of extravasation, suggesting that UAP may show progression to thrombosis and, thus, resolve spontaneously. CONCLUSIONS UAP may not be so rare and not associated with traumatic delivery/abortion. Some UAP may resolve, and, thus, may not require TAE, at least immediately.

AGEs and HMGB1 Increase Inflammatory Cytokine Production from Human Placental Cells, Resulting in an Enhancement of Monocyte Migration

Advanced glycation end products (AGEs) and high‐mobility group box‐1 (HMGB1) are considered contributing to placental inflammation. We examined the effect of AGEs and HMGB1 on cytokines from Sw.71 human trophoblast cell lines and the interactions between Sw.71 cells and THP‐1‐monocytes.

Moderate Hypoxia Down-Regulates Interleukin-6 Secretion and TLR4 Expression in Human Sw.71 Placental Cells

Background/Aims: The placenta is a vital organ for pregnancy. Many in vitro placental experiments are conducted under 21% O2; however, O2 tension could influence cellular functions, including cytokine secretion. We investigated the effects of oxygen tension between moderate hypoxia (5% O2) and normoxia (21% O2) by testing the hypothesis that moderate hypoxia regulates cellular phenotypes differently from normoxia in human trophoblast cells. Methods and Results: Sw.71 trophoblast cells were incubated under normoxic or moderately hypoxic conditions. Cells were also treated with lipopolysaccharide (LPS) as a Toll-like receptor 4 (TLR4) ligand inducing inflammation. Interleukin-6 (IL-6) as an inflammatory cytokine was determined, and TLR4, hypoxia-induced factor-1α (HIF1α), and reactive oxygen species (ROS) production were detected. Moderate hypoxia increased HIF1α expression and cell proliferation and acted by two different mechanisms to decrease IL-6 secretion compared with normoxia: it limits the TLR4 expression and ROS production. Treatment with cobalt chloride as an HIF1 activator inhibited IL-6 secretion and TLR4 expression; this effect was reversed on treatment with PX-12 as an HIF1 suppressor. Conclusion: IL-6 secretion, TLR4 expression, and ROS production, classical markers of inflammation, are down-regulated by moderate hypoxia, and HIF1α and ROS have a potential to regulate these responses in human trophoblast cells.

The ovarian artery: An unusual feeding artery of uterine artery pseudoaneurysm necessitating repetitive transarterial embolisation

Uterine artery pseudoaneurysm (UAP) sometimes causes life-threatening post-partum or post-abortal haemorrhage. Transarterial embolisation (TAE) for the uterine artery is considered the optimal trea...

The Frequency of Peripheral Blood CD4+FoxP3+ Regulatory T Cells in Women With Pre-eclampsia and Those With High-risk Factors for Pre-eclampsia

Objective: We compared the frequency of peripheral blood Treg cells in women with pre-eclampsia (PE) and in those without, and investigated whether the frequency of Treg cells in women with high-risk factor for PE changed during pregnancy. Methods: We examined the frequency of CD4+FoxP3+ Treg cells in the peripheral blood using flow cytometry. Eleven women with PE and 10 women without PE (controls) were included. Every control had any risk factors for PE, such as high blood pressure, bilateral notching or a past history of PE or gestational hypertension. Blood sampling was conducted 1–3 times in the controls. Results: No significant differences were observed in the frequency of Treg cells between women with PE and the controls [mean ± SE (%): 5.74 ± 0.91 versus 5.48 ± 0.94, p = 0.843]. In five controls with serial sampling, the frequency of Treg cells significantly decreased from 5.83 ± 1.20 to 2.99 ± 0.54 (p = 0.046) (week of the first sampling to that of the last sampling [mean ± SD]: 21.5 ± 1.6 weeks to 31.2 ± 2.5 weeks). Conclusion: The frequency of Treg cells in women with PE was almost identical to that in the controls. The frequency of Treg cells in the controls was reduced by half from the second trimester to the third trimester. These results suggested that the levels of Treg cells in a high-risk pregnant cohort were decreased to those in women with PE in the third trimester irrespective of the occurrence of PE.

Pancytopenia in the first trimester: An indicator of hidden hyperthyroidism

Pancytopenia in the first trimester is very rare. A 33‐year‐old multiparous woman presented with nausea, loss of appetite, and bodyweight loss of 7.4 kg at 91/7 weeks of gestation due to hyperemesis gravidarum. Her laboratory data demonstrated pancytopenia involving white blood cell count of 3500/μL, a hemoglobin level of 9.8 g/dL, and a platelet count of 10.5 × 104/μL. An extensive investigation into the causes of the pancytopenia detected true hyperthyroidism: thyroid‐stimulating hormone, <0.02 μU/mL; free triiodothyronine, 11.25 pg/mL; free thyroxine, 4.74 ng/dL; and anti‐thyroid‐stimulating hormone receptor antibodies, 12.2 IU/L. Propylthiouracil was started at a dose of 300 mg/day at 105/7 weeks of gestation, which resulted in the normalization of her blood parameters and concomitant improvements in her free triiodothyronine and free thyroxine levels at 120/7 weeks of gestation. Pancytopenia in the first trimester might be indicative of hidden hyperthyroidism.

Increased serum levels of sFlt-1/PlGF ratio in preeclamptic women with onset at <32 weeks compared with ≥32 weeks

OBJECTIVE Our first aim was to construct gestational-age-specific reference ranges of serum levels of soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), and the sFlt-1/PlGF ratio at 19-38 weeks of gestation. Our second aim was to compare the serum levels of sFlt-1, PlGF, and the sFlt-1/PlGF ratio in 81 women with PE which occurred at <32, 32-33, 34-35, and ≥36 weeks. METHOD Serum levels of sFlt-1 and PlGF were measured by automated immunoassays (Elecsys sFlt-1 and Elecsys PlGF). We constructed the normal reference ranges of log10sFlt-1, log10PlGF, and the log10(sFlt-1/PlGF) between 19 and 38 weeks using 309 samples, which could be represented by a quadratic curve. The cut-off levels were defined as the 5th and 95th percentiles of their gestational-age-specific reference ranges. RESULTS The frequencies of high sFlt-1, low PlGF, and a high sFlt-1/PlGF ratio in women with an onset at <32 weeks were all 100%, whereas there were no groups showing 100% abnormalities of sFlt-1, PlGF or the sFlt-1/PlGF ratio in women with an onset at 32-33, 34-35, and ≥36 weeks. The levels of sFlt-1, PlGF, and the sFlt-1/PlGF ratio in women with an onset at <32 weeks were significantly different from those in women with an onset at ≥32-33 weeks, although the levels of sFlt-1, PlGF, and the sFlt-1/PlGF ratio in women with an onset at 32-33, 34-35, and ≥36 weeks were almost the same. CONCLUSION The appropriate threshold weeks for defining early-onset PE might be 32+0 weeks rather than 34+0 or 36+0 weeks.

Hysterectomy for cesarean scar pregnancy: no or minimal bladder separation technique

Sir, For cesarean scar pregnancy (CSP), various uterus-preserving treatments have been proposed; however, hysterectomy is eventually required in some cases (1,2). Hysterectomy-related adverse events should be avoided, especially in CSP-hysterectomy, considering that patients are usually exhausted or compromised both mentally and physically after failed uterus-preserving therapy. Bladder separation during CSP-hysterectomy often causes bladder injury (Figure 1a). CSP is located in the anterior lower uterine segment just beneath the bladder posterior wall, bulging into the bladder, with both tightly adhering to each other. Failed uterus-preserving treatment causes local tissue weakness. Such injury may be avoided by a new procedure. The uterine artery (ascending branch) is cut. Posterior and upper parts of the parametrium should be cut and ligated, freeing the uterine lateral/posterior side. The bladder should be filled with 200–400 mL of saline (filling the bladder technique) (3), which clearly shows the bladder-cephalad edge, a bladderseparation starting site. Importantly, separation should be minimal or completely avoided depending on the CSP location. A short-distance separation (1–3 cm) is usually sufficient to confirm the CSP site. Here, the uterus should be amputated, with the CSP lesion being attached to the amputated uterus; thereby, the CSP lesion can be removed as extensively as possible (Figure 1b), similar to the “amputation first technique” devised for hysterectomy for placenta percreta (4). In this stage, “complete” CSP removal is not needed. After uterus amputation, the CSP lesion, if it remains, should be removed from the cervix luminal side, with suture-ligation performed to achieve hemostasis if necessary. Then, the anterior and posterior cervical walls should be sutured, closing the cervix. Usually, the needle

Serum soluble LIGHT in the early third trimester as a novel biomarker for predicting late-onset preeclampsia

Our aim was to evaluate whether serum levels of soluble LIGHT (sLIGHT) at 27-31 weeks can predict the later occurrence of gestational hypertension (GH), late-onset preeclampsia (PE), and early-onset PE. Mean blood pressure (MBP), soluble fma-like tyrosine kinase 1/placental growth factor (sFlt-1/PlGF) ratio at 27-31 weeks, and sLIGHT at 27-31 weeks were independent risk factors for late-onset PE. The combination of the three risk factors improved sensitivity with a false-positive rate of 10% (MBP: 60%, log10(sFlt-1/PlGF): 45%, sLIGHT: 35%, combination: 75%). Serum sLIGHT in the early third trimester may be a novel biomarker for predicting late-onset PE.

Markedly higher sFlt-1/PlGF ratio in a woman with acute fatty liver of pregnancy compared with HELLP syndrome: sFlt-1/PlGF ratio in AFLP and HELLP

To compare serum levels of angiogenesis‐related factors between 14 women with HELLP (hemolysis, elevated liver enzymes and low platelet count) syndrome and a woman with acute fatty liver of pregnancy (AFLP).