Dendritic cells (DC) as professional antigen presenting cells are able to prime T-cells against the tumor-associated antigen α-fetoprotein (AFP) for immunotherapy of hepatocellular carcinoma (HCC). However, a strong immunosuppressive tumor environment limits their efficacy in patients. The co-stimulation with CD40Ligand (CD40L) is critical in the maturation of DC and T-cell priming. In this study, the impact of intratumoral (i.t.) CD40L-expressing DC to improve vaccination with murine (m)AFP-transduced DC (Ad-mAFP-DC) was analyzed in subcutaneous (s.c.) and orthotopic murine HCC. Murine DC were adenovirally transduced with Ad-mAFP or Ad-CD40L. Hepa129-mAFP-cells were injected into the right flank or the liver of C3H-mice to induce subcutaneous (s.c.) and orthotopic HCC. For treatments, 10⁶ Ad-mAFP-transduced DC were inoculated s.c. followed by 10⁶ CD40L-expressing DC injected intratumorally (i.t.). S.c. inoculation with Ad-mAFP-transduced DC, as vaccine, induced a delay of tumor-growth of AFP-positive HCC compared to controls. When s.c.-inoculation of Ad-mAFP-DC was combined with i.t.-application of Ad-CD40L-DC synergistic antitumoral effects were observed and complete remissions and long-term survival in 62% of tumor-bearing animals were achieved. Analysis of the tumor environment at different time points revealed that s.c.-vaccination with Ad-mAFP-DC seems to stimulate tumor-specific effector cells, allowing an earlier recruitment of effector T-cells and a Th1 shift within the tumors. After i.t. co-stimulation with Ad-CD40L-DC, production of Th1-cytokines was strongly increased and accompanied by a robust tumor infiltration of mature DC, activated CD4⁺-, CD8⁺-T-cells as well as reduction of regulatory T-cells. Moreover, Ad-CD40L-DC induced tumor cell apoptosis. Intratumoral co-stimulation with CD40L-expressing DC significantly improves vaccination with Ad-mAFP-DC in pre-established HCC in vivo. Combined therapy caused an early and strong Th1-shift in the tumor environment as well as higher tumor apoptosis, leading to synergistic tumor regression of HCC. Thus, CD40L co-stimulation represents a promising tool for improving DC-based immunotherapy of HCC.

This study aimed to evaluate the diagnostic and prognostic value of cardiac magnetic resonance in acute peripartum cardiomyopathy (PPCM). A total of 17 patients with PPCM in the acute stage and 15 healthy controls were retrospectively analyzed regarding myocardial function, edema, late gadolinium enhancement (LGE), and T1 and T2 mappings (T1, T2). Echocardiographic follow-ups were performed. Functional recovery was defined as a left ventricular ejection fraction (LVEF) of ≥50%. Patients with PPCM displayed biventricular dysfunction with reduced myocardial strain parameters and left ventricular and atrial dilatation, as well as diffuse myocardial edema (T2 signal intensity ratio: 2.10 ± 0.34 vs. 1.58 ± 0.21, p < 0.001; T1: 1070 ± 51 ms vs. 980 ± 28 ms, p = 0.001; T2: 63 ± 5 ms vs. 53 ± 2 ms, p < 0.001). Visual myocardial edema was present in 10 patients (59%). LGE was positive in 2 patients (12%). A total of 13 patients (76%) showed full LVEF recovery. The absence of visual myocardial edema and impairment of strain parameters were associated with delayed LVEF recovery. Multivariable Cox regression analysis revealed global longitudinal strain as an independent prognostic factor for LVEF recovery. In conclusion, biventricular systolic dysfunction with diffuse myocardial edema seems to be present in acute PPCM. Myocardial edema and strain may have prognostic value for LVEF recovery.

Background: To report on prophylactic therapy for hyperfibrinolysis with tranexamic acid (TXA) during expectant management (EM) in the placenta accreta spectrum (PAS). Methods: This is a monocentric retrospective study of women with PAS presenting at our hospital between 2005 and 2021. All data were retrospectively collected through the departmental database. Results: 35 patients with PAS were included. EM was planned in 25 patients prior to delivery. Complete absorption of the retained placenta was seen in two patients (8%). Curettage was performed in 14 patients (56%). A hysterectomy (HE) was needed in seven (28%) patients; 18 patients (72%) underwent uterus-preserving treatment without severe complications. The mean duration of EM was 107 days. The mean day of onset of hyperfibrinolysis and beginning of TXA treatment was day 45. The mean nadir of fibrinogen level before TXA was 242.4 mg/dL, with a mean drop of 29.7% in fibrinogen level. Conclusions: Our data support EM as a safe treatment option in PAS. Hyperfibrinolysis can be a cause of hemorrhage during EM and can be treated with TXA. To our knowledge, this is the first cohort of patients with EM of PAS in whom coagulation monitoring and use of TXA have been shown to successfully treat hyperfibrinolysis.

Background: Portal hypertension in pregnancy is characterized by an increased perinatal and maternal complication rate. The purpose of this study was to evaluate the perinatal and maternal outcomes of these high-risk pregnancies at our tertiary center. Methods: We identified pregnancies with portal hypertension in our departmental database for the years 2013 to 2021. The medical history and perinatal and maternal data were extracted from medical records. Results: Eleven cases were identified. In pregnancy, delivery and postpartum, complications occurred in 72.7% of cases and included among others ascites, subclavian thrombosis, variceal-ligation-induced ulcer bleeding and postoperative hemorrhage. The cesarean delivery rate was 72.7% (n = 8); five of these were done for obstetric or fetal indications. The rate of preterm birth and admissions to neonatal intensive care unit were high (54.5% and 45.5%, respectively). Conclusions: Our case series substantiates the high maternal and perinatal complication rates seen in portal hypertension. The prevention of thromboembolic and bleeding complications was the main challenge. Care by an interdisciplinary team of experts is crucial for a successful perinatal and maternal outcome.

Objectives: Pregnancies in women with Fontan circulation are on the rise, and they are known to imply high maternal and fetal complication rates. The altered hemodynamic profile of univentricular circulation affects placental development and function. This study describes placental sonomorphologic appearance and Doppler examinations and correlates these to histopathologic findings and pregnancy outcomes in women with Fontan circulation. Methods: A single-center retrospective analysis of pregnancies in women with Fontan circulation was conducted between 2018 and 2023. Maternal characteristics and obstetric and neonatal outcomes were recorded. Serial ultrasound examinations including placental sonomorphologic appearance and Doppler studies were assessed. Macroscopic and histopathologic findings of the placentas were reviewed. Results: Six live births from six women with Fontan physiology were available for analysis. Prematurity occurred in 83% (5/6 cases) and fetal growth restriction and bleeding events in 66% (4/6 cases) each. All but one placenta showed similar sonomorphologic abnormalities starting during the late second trimester, such as thickened globular shape, inhomogeneous echotexture, and hypoechoic lakes, resulting in a jelly-like appearance. Uteroplacental blood flow indices were within normal range in all women. The corresponding histopathologic findings were non-specific and consisted of intervillous and subchorionic fibrin deposition, villous atrophy, hypoplasia, or fibrosis. Conclusions: Obstetric and perinatal complication rates in pregnancies of women with Fontan circulation are high. Thus, predictors are urgently needed. Our results suggest that serial ultrasound examinations with increased awareness of the placental appearance and its development, linked to the Doppler sonographic results of the uteroplacental and fetomaternal circulation, may be suitable for the early identification of cases prone to complications.