sFlt-1/PlGF ratio predicts serious outcomes in confirmed early-onset preeclampsia.

OBJECTIVES: We aimed to determine whether a high ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) would be associated with serious negative consequences and shorter pregnancy duration in cases of early-onset preeclampsia (PE). STUDY DESIGN: This retrospective cohort study included women (n = 65) diagnosed with PE at <34.0 weeks of gestation and recruited from a single primary and tertiary medical centre in Japan. The sFlt-1/PlGF ratio in the study participants was measured. To determine the optimal threshold for the sFlt-1/PlGF ratio, a receiver operating characteristic curve was employed, with the aim of predicting serious adverse outcomes within 1 week after serum angiogenic marker measurements. We performed Kaplan-Meier analysis and the log-rank test to assess delivery probability based on the sFlt-1/PlGF ratio. RESULTS: Thirty-seven women (56.9 %) delivered within 1 week of serum angiogenic marker measurements due to the aggravation of early-onset preeclampsia. Women who developed serious adverse outcomes within 1 week had a significantly higher sFlt-1/PlGF ratio than that of women who did not develop serious complications (408.5 vs. 166.6, P < 0.001). A cut-off value of 224.6 for the sFlt-1/PlGF ratio predicted serious adverse outcomes, with a sensitivity of 81.1 % and a specificity of 71.4 % (area under the curve: 0.77). Moreover, 78.9 % of women with an sFlt-1/PlGF ratio ≥ 224.6 compared to 25.9 % of those with an sFlt-1/PlGF ratio < 224.6 delivered within 1 week of presentation (P < 0.001). CONCLUSIONS: Women with confirmed early-onset preeclampsia and high sFlt-1/PlGF ratio are more likely to develop serious adverse outcomes within 1 week after serum angiogenic marker measurements.

Preeclampsia prediction model using demographic, clinical, and sonographic data in the second trimester of Japanese nulliparous women.

AIM: This study aimed to clarify the factors influencing preeclampsia (PE) development in nulliparous Japanese women and to develop a PE prediction model using second trimester sonographic and clinical data readily available to obstetricians. METHODS: This historical cohort study examined the obstetric records of nulliparous women who delivered at Yamanashi Prefectural Central Hospital from January 2019 to May 2023. A model was constructed to predict the PE development rate, with a focus on 796 nulliparous women. The assessed outcome was PE, excluding superimposed PE. Data on maternal age, assisted reproductive technology, mean arterial pressure, uterine artery notching, and umbilical artery resistance index were extracted. Multivariable logistic regression analysis was conducted on these five factors. RESULTS: The incidence of PE was 4.3% (34/796). Multivariable analysis indicated significant odds ratios for the association of PE with mean arterial pressure (adjusted odds ratio: 1.06, 95% confidence interval: 1.03-1.10) and uterine artery notching (adjusted odds ratio: 6.28, 95% confidence interval: 2.82-14.0) in nulliparous women. The PE prediction formula was established as follows: Probability of PE development (%) = (odds/1 + odds) × 100, odds = ex and x = -11.3 + 0.039 × maternal age (years) + 0.91 × assisted reproductive technology + 0.061 × mean arterial pressure (mmHg) + 1.84 × uterine artery notching + 1.84 × umbilical artery resistance index. The sensitivity and specificity of this model were 58.8% and 84.5%, respectively (area under the curve: 0.79). CONCLUSIONS: This study is the first to provide a prediction formula targeting the Japanese population. Our specialized model for nulliparous women could guide obstetricians to educate women regarding the precise prospect of PE development.

Utility of the angle between the cervical canal and the anatomical conjugate line for predicting pouch of Douglas obliteration in patients with posterior placenta previa.

AIM: Pouch of Douglas obliteration, which prevents exteriorization of the uterus, increases surgical morbidity in patients with placenta previa. We aimed to identify magnetic resonance imaging features that can predict pouch of Douglas obliteration preoperatively. METHODS: We retrospectively assessed 39 women with posterior placenta previa who underwent magnetic resonance imaging for the preoperative assessment of placenta accreta spectrum. We defined the angle formed by the anatomical conjugate line (based on pelvimetry) and the cervical canal as the cervical inclination angle, which was measured on sagittal T2-weighted magnetic resonance imaging. Subsequently, we analyzed the correlation between the cervical inclination angle and pouch of Douglas obliteration. RESULTS: The median maternal age was 34 years (range, 22-44 years) and 26 (66.7%) women delivered at term. The median cervical inclination angle was 98° (range, 71-128). Pouch of Douglas obliteration was confirmed in six patients (15.4%). The cut-off value of the cervical inclination angle for the prediction of pouch of Douglas obliteration was 102° with a sensitivity of 66.7%, specificity of 78.8%, positive predictive value of 36.4%, and negative predictive value of 92.9% (area under the curve, 0.83). CONCLUSIONS: Measuring the cervical inclination angle may help in ruling out an obliteration of the pouch of Douglas. It may also be useful in the operative management of women with posterior placenta previa. However, caution should be exercised when generalizing the results of this study because of the small sample size, which makes the results prone to bias.

Association between α-defensin 5 and the expression and function of P-glycoprotein in differentiated intestinal Caco-2 cells.

α-Defensin 5 is known to be secreted by Paneth cells in the small intestine and plays an important role in eliminating pathogenic microorganisms. It has been reported that a decrease in α-defensin 5 level in the human small intestine is a risk of inflammatory bowel disease (IBD). Furthermore, P-glycoprotein (P-gp), a member of the ATP-binding cassette transporter superfamily, encoded by the ABCB1/MDR1 gene, plays an important role in the front line of host defense by protecting the gastrointestinal barrier from xenobiotic accumulation and may contribute to the development and persistence of IBD. Therefore, we examined the relationship between α-defensin 5 and the expression and function of P-gp using a human gastrointestinal model cell line (Caco-2). We found that MDR1 mRNA and P-gp protein level were increased in Caco-2 cells as well as α-defensin 5 secretion corresponded with the duration of cell culture. Exposure to α-defensin 5 peptide and recombinant tumor necrosis factor-α (TNF-α) significantly increased the expression and function P-gp. The mRNA levels of interleukin (IL)-8, IL-6, TNF-α, IL-1ß, and IL-2 were also increased following exposure to TNF-α, similar to α-defensin 5 treatment. These results suggest that α-defensin 5 regulates P-gp expression and function by increasing TNF-α expression in Caco-2 cells.

A modified transabdominal cervicoisthmic cerclage with the monofilament thread: Its efficacy and safety for women with extremely short cervix due to cervical conization.

AIM: The study aimed to examine the usefulness of modified transabdominal cervicoisthmic cerclage (TAC) using monofilament thread for the prevention of preterm delivery in women with an extremely short cervix after deep conization. METHODS: We devised a monofilament thread for picking up the seromuscular layer of the site that is slightly cephalad to the internal ostium to prevent injury of the vessels around the uterine cervix. From 2017 to 2020, we performed this modified operation in eight women (nine pregnancies) at 12-16 weeks of gestation with a history of deep cervical conization. RESULTS: A modified TAC was successfully performed in all patients. There was no measurable bleeding, and all patients were discharged without postoperative complications. Their pregnancy courses after the operation were uneventful. Of nine, one patient had premature uterine contractions and underwent cesarean section at 36 weeks (preterm delivery). In the other eight pregnancies, planned cesarean section was performed after 37 weeks of gestation. The median birth weight of the babies was 2996 g (range 2604-3374 g). All patients were discharged on the sixth postoperative day without complications. CONCLUSION: A modified TAC can be safely performed and may prolong pregnancy without adverse events in patients with an extremely short cervix.

Predictive value of the sFlt-1/PlGF ratio for preeclampsia in twin pregnancies: a retrospective study.

Objective: This study aimed to investigate the efficiency of the soluble Fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio in predicting preeclampsia (PE) within 4 weeks in twin pregnancies.Methods: Seventy-eight women with serum angiogenic markers measured at 28 + 0 to 30 + 6 weeks of gestation were enrolled. A receiver-operating characteristic curve was used to determine the sFlt-1/PlGF ratio threshold to predict PE.Results: A cutoff value for the sFlt-1/PlGF ratio of 22.2 predicted PE presence within 4 weeks.Conclusion: An sFlt-1/PlGF ratio of ≤22.2 is potentially indicative of PE absence within 4 weeks in twin pregnancies.

Analysis of α-Defensin 5 Secretion in Differentiated Caco-2 Cells: Comparison of Cell Bank Origin.

α-Defensin 5 has a particularly broad antibacterial spectrum; it eliminates pathogenic microorganisms and regulates intestinal flora. Although Caco-2 cells are similar to small intestinal cells, it is unclear whether they secrete α-defensin 5. Therefore, we investigated whether Caco-2 cells secrete α-defensin 5 and determined the secretion mechanism using cells from three cell banks (ATCC, DSMZ, and RIKEN). The Caco-2 cell proliferation rate increased with the number of culture days, irrespective of cell bank origin. On the other hand, the alkaline phosphatase activity, which affects cell differentiation and the mRNA levels of several cytokines, such as interleukin 8 (IL-8), IL-6, IL-1ß, tumor necrosis factor-α (TNF-α), and IL-2, in the Caco-2 cells fluctuated with the number of culture days, and differed for each cell bank. α-Defensin 5 secretion was detected in all three cell bank Caco-2 cells; particularly, the ATCC Caco-2 cells grew linearly depending on the cell culture day as well as the levels of IL-8 and TNF-α mRNA. This suggested that α-defensin 5 secretion in the ATCC Caco-2 cells was associated with fluctuations in the mRNA levels of various cytokines, such as IL-8 and TNF-α. In conclusion, Caco-2 cells may be a simple model for screening health food components and drugs that affect α-defensin 5 secretion.

Gamma-Aminobutyric Acid (GABA) Attenuates Ischemia Reperfusion-Induced Alterations in Intestinal Immunity.

The aims of this study were to determine the effects of gamma-aminobutyric acid (GABA) on immunoglobulin A (IgA) secretion from Peyer's patch (PP) cells; to assess rat alpha-defensin-5 (RD-5) expression in the rat small intestine; and to determine the effect of GABA on intestinal ischemia reperfusion (I/R) injury-induced intestinal innate immunity. We found that GABA caused an increase in IgA secretion in the presence and absence of lipopolysaccharide (LPS). Moreover, GABA also significantly increased the mRNA levels of RD-5 and superoxide dismutase (Sod) 1, 3. Intestinal I/R was induced by a 30-min occlusion of the superior mesenteric artery followed by a reperfusion for 60-min. This led to a significant decrease in IgA secretion, and mRNA levels of RD-5 and Sod 1-3 in the ileum. On the other hand, administration of GABA before I/R induction had a significant protective effect against oxidative injury and attenuated the effects on intestinal immunity.