Delayed interval delivery in multiple gestations: the Munich experience.

OBJECTIVE: To evaluate delayed interval deliveries in multiple gestations in regard of delayed interval and neonatal survival and to provide a protocol. METHODS: Data of multiple pregnancies with delayed interval delivery at a tertiary maternity unit between 2002 and 2017 were collected. Contraindications for evaluation of a delay of the delivery of the remaining child were: severe maternal blood loss, poor maternal general condition, preeclampsia, placental abruption, fetal distress, serious congenital malformations of the remaining child, chorioamnionitis, and premature rupture of membranes of the second fetus. A total of 14 cases was included in this retrospective monocentric analysis. RESULTS: The cohort comprised nine twin and five triplet pregnancies. Mean gestational age at delivery of the first fetus was 21 + 6 and 26 + 0 of the retained fetus, respectively. The earliest delivery of the first fetus was at 15 + 2 weeks. The mean interval of the delay was 29.3 days (2-82 days). Mortality of the first fetuses was 53.3%, while it was 17.6% for the retained fetuses. Maternal outcome was good in general: two cases of major blood loss occurred with the necessity of a blood transfusion. CONCLUSION: Delayed interval delivery is a reasonable approach in cases of an imminent preterm birth in multiple gestations which can be performed with a good fetal outcome and limited maternal risks. The situation when this procedure may be an option always comes unexpected. Therefore, the team of perinatologists should keep it in mind as one potential therapeutic approach. In addition, a standard protocol for the procedure should be established in the perinatal center.

Increased TGF-ß: a drawback of tracheal occlusion in human and experimental congenital diaphragmatic hernia?

Survivors of severe congenital diaphragmatic hernia (CDH) present significant respiratory morbidity despite lung growth induced by fetal tracheal occlusion (TO). We hypothesized that the underlying mechanisms would involve changes in lung extracellular matrix and dysregulated transforming growth factor (TGF)-ß pathway, a key player in lung development and repair. Pulmonary expression of TGF-ß signaling components, downstream effectors, and extracellular matrix targets were evaluated in CDH neonates who died between birth and the first few weeks of life after prenatal conservative management or TO, and in rabbit pups that were prenatally randomized for surgical CDH and TO vs. sham operation. Before tissue harvesting, lung tissue mechanics in rabbits was measured using the constant-phase model during the first 30 min of life. Human CDH and control fetal lungs were also collected from midterm onwards. Human and experimental CDH did not affect TGF-ß/Smad2/3 expression and activity. In human and rabbit CDH lungs, TO upregulated TGF-ß transcripts. Analysis of downstream pathways indicated increased Rho-associated kinases to the detriment of Smad2/3 activation. After TO, subtle accumulation of collagen and α-smooth muscle actin within alveolar walls was detected in rabbit pups and human CDH lungs with short-term mechanical ventilation. Despite TO-induced lung growth, mediocre lung tissue mechanics in the rabbit model was associated with increased transcription of extracellular matrix components. These results suggest that prenatal TO increases TGF-ß/Rho kinase pathway, myofibroblast differentiation, and matrix deposition in neonatal rabbit and human CDH lungs. Whether this might influence postnatal development of sustainably ventilated lungs remains to be determined.

The risk of non-sentinel metastases in primary breast cancer.

BACKGROUND: Sentinel node biopsy (SNB) has been established as standard of surgical care in primary breast cancer. If the sentinel node (SN) is negative, axillary dissection (ALND) is not necessary, but if the SN is positive ALND is warranted. This analysis evaluated associated risk factors for non-sentinel metastases in the case of a positive SN. PATIENTS AND METHODS: A retrospective analysis of all SNB performed between 10/1999 and 07/2005 was carried out. RESULTS: A total of 406 patients were included: 214 patients (51%) had SNB with ALND while 197 patients (49%) had SNB only. In 41 of 109 nodal-positive patients, the SN was the only nodal metastasis. In the multivariate analysis, the number of positive SN and the presence of lymphatic vessel infiltration were significant risk factors for additional non-sentinel metastases (p = 0.05 and 0.047, respectively). The risk for non-sentinel metastases was 25.9% without and 59.2% with these risk factors, respectively. CONCLUSION: If the SN is positive, ALND remains obligatory.