Effect of remission, clinical remission with active serology, and glucocorticoid dosage on the pregnancy outcome of pregnant patients with systemic lupus erythematosus.

BACKGROUND: Remission is a key treatment target in systemic lupus erythematosus (SLE) management. Given the direct correlation between lupus flares and elevated risks of adverse pregnancy outcomes (APOs), securing remission before conception becomes crucial. However, the association between clinical remission with active serology, and the risk of APOs is not thoroughly understood. Additionally, determining the optimal glucocorticoid dosage during pregnancy to mitigate APO risks remains under-researched. This study investigated the risk of APOs in relation to remission/serological activity status in patients in clinical remission/glucocorticoid dosage. METHODS: Pregnant patients with SLE, who were followed up at two Japanese tertiary referral centers, and had their remission status assessed at conception, were included in this study. We categorized the patients into two groups based on whether they achieved Zen/Doria remission at conception and analyzed the APO ratio. We also examined the influence of serological activity in pregnant patients with clinical remission and analyzed the optimal glucocorticoid dosage to minimize the APO ratio. RESULTS: Of the 96 pregnancies included, 59 achieved remission at conception. Pregnant patients who achieved remission showed a significant decrease in the APO ratio compared with those who did not. (overall APO: odds ratio (OR) 0.27, 95% confidence interval (CI) 0.11-0.65, p < 0.01, maternal APO: OR 0.34, 95%CI 0.13-0.85, p = 0.021, neonatal APO: OR 0.39, 95%CI 0.17-0.90, p = 0.028). Conversely, no statistical difference was observed in the APO ratio based on serological activity in pregnant patients with clinical remission. (overall APO: OR 0.62, 95%CI 0.21-1.79, p = 0.37, maternal APO: OR 1.25, 95%CI 0.32-4.85, p = 0.75, neonatal APO: OR 0.83, 95%CI 0.29-2.39, p = 0.73). A glucocorticoid dose of prednisolone equivalent ≥ 7.5 mg/day at conception correlated with increased APO. (overall APO: OR 3.01, 95%CI 1.23-7.39, p = 0.016, neonatal APO: OR 2.98, 95% CI:1.23-7.22, p = 0.016). CONCLUSIONS: Even with active serology, achieving clinical remission can be a clinical target for reducing APOs in patients who wish to conceive. In addition, if clinically feasible, reducing the glucocorticoid dosage to < 7.5 mg/day before conception could be another predictive factor.

A retrospective analysis of the safety of tacrolimus use and its optimal cut-off concentration during pregnancy in women with systemic lupus erythematosus: study from two Japanese tertiary referral centers.

BACKGROUND: Tacrolimus is one of the major treatment options for systemic lupus erythematosus (SLE) and is considered to be a pregnancy-compatible medication. Since little is known about tacrolimus safety during pregnancy complicated by SLE, this study was designed. METHODS: We included SLE pregnant patients who were followed up at two Japanese tertiary referral centers. We performed multivariate logistic regression analysis to assess each adverse pregnancy outcome (APO) risk. Moreover, we assessed the influence of tacrolimus on the APO ratio in pregnant patients with lupus nephritis, and the impact of combined tacrolimus-aspirin therapy on the APO ratio relative to patients exclusively administered tacrolimus. RESULTS: Of the 124 pregnancies, 29 were exposed to tacrolimus. Multivariate analysis showed no statistical difference in APO ratio. (overall APO: adjusted odds ratio [aOR], 0.69; 95% confidence interval [CI], 0.23-2.03; p = 0.50; maternal APO: aOR, 1.17; 95% CI, 0.36-3.83; p = 0.80; neonatal APO: aOR, 1.10; 95% CI, 0.38-3.21; p = 0.86; PROMISSE APO: aOR, 0.50; 95% CI, 0.14-1.74; p = 0.27). Blood pressure and estimated glomerular filtration rate (eGFR) during pregnancy and after delivery did not differ between the two groups. Receiver operating characteristic (ROC) curve showed that tacrolimus concentration > 2.6 ng/ml was related to reduced preterm birth rate. (AUC = 0.85, 95% CI: 0.61-1.00, sensitivity: 93% and specificity: 75%). Regarding effect of tacrolimus on lupus nephritis during pregnancy, tacrolimus showed no increased risk of APO, blood pressure or eGFR during pregnancy and after delivery. (overall APO: OR, 1.00; 95% CI, 0.25-4.08; p = 0.98; maternal APO: OR 1.60, 95% CI, 0.39-6.64; p = 0.51; neonatal APO: OR, 0.71; 95% CI, 0.17-3.03; p = 0.65, PROMISSE APO: OR, 0.50; 95% CI, 0.08-3.22; p = 0.47). Tacrolimus-aspirin combination therapy showed a protective tendency against hypertensive disorders during pregnancy, preeclampsia and low birth weight. CONCLUSIONS: Tacrolimus use during pregnancy with SLE and lupus nephritis showed no significant influence on APO, blood pressure, or renal function; therefore tacrolimus may be suitable for controlling lupus activity during pregnancy. In addition, when using tacrolimus during pregnancy, we should aim its trough concentration ≥ 2.6 ng/ml while paying careful attention to possible maternal side effects of tacrolimus. TRIAL REGISTRATION: Retrospectively registered.

Changes in the Ultrasonographical Appearance of Intertwin-Dividing Membrane of Monochorionic Diamniotic Twin Pregnancy.

Ultrasound determination of chorionicity in the first trimester has a high accuracy, but it is associated with some pitfalls. This report presents changes in ultrasound findings during a monochorionic pregnancy with chorionic membrane folding (CMF). The patient was a 32-year-old woman, gravida 2 para 0. Her transvaginal ultrasonography identified two gestational sacs (GSs) and two embryos at 7 weeks of gestation. At 9 weeks' gestation, an ultrasound image showed a lambda sign at both sides and the interruption of chorionic membranes, resulting in the diagnosis of a monochorionic diamniotic (MCDA) twin pregnancy with CMF. At 11 weeks' gestation, an ultrasound image showed a lambda sign at one portion of the septum and a T sign at another portion. This change suggested that the folded chorionic membrane had partially flattened. At 35 weeks' gestation, an emergency cesarean section was performed. Two healthy male neonates were delivered. Histological placental examination confirmed that the intertwin membrane was composed of two amniotic membranes without a folded chorionic membrane, confirming the diagnosis of a MCDA twin pregnancy. This case presents two important ultrasound chorionicity findings: a monochorionic pregnancy with CMF can show two GSs and a lambda sign and the CMF can flatten or change during the pregnancy.

Abnormal Urine Outflow from the Ureteral Orifice on Cystoscopy Following Vaginal Stump Suture in Total Laparoscopic Hysterectomy.

OBJECTIVES: Ureteral injuries may occur subsequent to abdominal or laparoscopic hysterectomy. In total laparoscopic hysterectomy (TLH), we usually check for ureteral damage by confirming urinary outflow from the bilateral ureteral orifices by cystoscopy after vaginal stump suture. In this work, we investigated the causes of urine outflow disruption after TLH. MATERIALS AND METHODS: We conducted a retrospective review of all TLHs performed for benign diseases at our hospital from February 2012 to March 2016. There were 11 cases with no or poor urine outflow from the ureteral orifice after vaginal stump suture. For these cases, we assessed the treatment to recover urine outflow and examined the cases with intraoperative manipulation. EZR version 1.25 was used for statistical analysis. Correlation coefficients were calculated with Spearman's rank correlation coefficient test. RESULTS: The abnormality was on the right and left sides in seven and four cases, respectively. In all cases, apart from one, urine outflow was recovered by removing the sutures at the affected side, where the initial suture had included a small amount of the connective tissue near the urinary bladder. It was inferred that ureteral deviation due to vaginal stump sutures that picked up the connective tissue near the ureter caused ureteral peristaltic disorder and abnormal ureteral orifice outflow. CONCLUSION: TLH without ureter isolation requires sufficient separation of the bladder from the anterior vaginal wall and careful vaginal stump suture without involving the bladder-side tissue to avoid ureteral injury.