Advancement of 3D printing technology for the development of a training model in US-guided vesicoamniotic shunting for early LUTO therapy.

INTRODUCTION: Prenatal lower urinary tract obstruction (LUTO) is a rare and challenging condition with potential severe morbidity and mortality. Prenatal shunting methods, specifically vesicoamniotic shunting (VAS) and fetal cystoscopy, aim to manage this condition. However, comprehensive education and training are hindered by the rarity of LUTO. To address this gap, we present a low-cost 3D-printed ultrasound training model for VAS in LUTO fetuses. The aim of the study was to evaluate ultrasound and haptic fidelity of the model. MATERIAL AND METHODS: Ultrasound images of three LUTO fetuses at 12-14 weeks were utilized to create detailed 3D-printed models. Fusion360TM software generated stereo-lithography files, and the Formlabs Form3® printer, using Flexible 80A resin, produced the models. A simulation box mimicking uterine conditions and fetal anatomy was developed for testing. Ultrasound assessments determined model accuracy, and expert evaluations gauged fidelity for VAS placement. RESULTS: The 3D-printed model accurately replicated LUTO fetal anatomy, demonstrating structural integrity and realistic sonographic and haptic feedback during 20 punctures. Macroscopic visualization confirmed the model's durability and authenticity. DISCUSSION: This innovative 3D-printed model addresses the scarcity of LUTO cases and the lack of realistic training tools. Simulation models enhance skills, providing a controlled learning environment that bridges theoretical knowledge and clinical application, potentially improving patient outcomes. CONCLUSIONS: The 3D-printed training model for VAS in LUTO represents a significant advancement in surgical education, offering realistic anatomical simulation and tactile feedback. Future studies should assess its effectiveness in enhancing surgical skills and impacting patient outcomes in clinical practice.

A comparative analysis of the Vasoactive-Inotropic Score, the Vasoactive-Ventilation-Renal Score, and the Oxygenation Index as outcome predictors in infants with a congenital diaphragmatic hernia.

OBJECTIVES: To date, different severity scores and indices are available to predict outcome in infants with a congenital diaphragmatic hernia (CDH). The Oxygenation Index (OI) and the Vasoactive-Inotropic Score (VIS) has already been evaluated in the CDH population. The Vasoactive-Ventilation-Renal (VVR) Score was recently evaluated as new severity score in several studies on infants with need for cardiac surgery. The score was shown to outperform the VIS and OI as outcome predictors in these infants, but no data are available regarding the evaluation of the VVR Score in CDH infants. PATIENTS AND METHODS: This was a retrospective single-center analysis at the University Children's Hospital, Bonn, Germany, during the study period from January 2019 until December 2022. Of 108 CDH infants treated at our institution, a final cohort of 100 neonates met the inclusion criteria. INCLUSION CRITERIA: diagnosis of CDH (right-sided, left-sided, or bilateral). EXCLUSION CRITERIA: early mortality (before surgical correction of the diaphragm), palliative care after birth, no available data for OI, VIS, and VVR Score calculation. The OI, the VIS, and the VVR Score were calculated at three selected timepoints: at 48-72 h after birth (T1), before surgery (T2), and after surgery (T3). MAIN RESULTS: The primary clinical endpoint (in-hospital mortality) was reached in 21% of the infants. Infants surviving to discharge were allocated to group A, infants with fatal outcome to group B. In the univariate analysis, the OI was significantly higher in infants allocated to group B at T2 (p < .001), and T3 (p < .001). The VIS was significantly higher only at T1 in infants allocated to group B (p = .001). The VVR Score was significantly higher at T1 (p = .017), and at T3 (p = .002) in infants not surviving to discharge. In the multivariate analysis, the OI at T2 + T3 (p < .001), the VIS at T1 (p = .048), and the VVR Score at T1 + T3 (p = .023, and p = .048, respectively) remained significantly associated with in-hospital mortality. The OI presented the highest area under the curve (AUC) at T2 and T3 (T2:0.867, p = .001; T3:0.833, p = .000) regarding the primary endpoint in the overall cohort. In the subgroup of infants without need for extracorporeal membrane oxygenation (ECMO) therapy (n = 60) the VVR Sore presented the best performance with an AUC of 0.942 (p = .000) at T3. CONCLUSION: The severity scores OI, VIS, and VVR-Score are independent predictors of in-hospital mortality in CDH infants. The OI seems to outperform the VIS and VVR-Score as outcome predictor immediately before and after CDH surgery, whereas the VVR Score presented the best performance in the subgroup of CDH infants without need for ECMO and mild-to-moderate CDH defects.

Risk Factors for Severe Pain and Impairment of Daily Life Activities after Cesarean Section-A Prospective Multi-Center Study of 11,932 Patients.

Cesarean section (CS) is the most widely performed and one of the most painful surgeries. This study investigated postoperative pain after CS using patient-related outcomes (PROs) to identify risk factors for severe pain. The secondary outcome was to evaluate the influence of surgery indication (primary CS (PCS) vs. urgent CS (UCS)). This multi-center, prospective cohort study included data submitted to the pain registry "quality improvement in postoperative pain treatment" (QUIPS) between 2010 and 2020. In total, 11,932 patients were evaluated. Median of maximal pain was 7.0 (numeric rating scale (NRS) 0 to 10); 53.9% suffered from severe pain (NRS ≥ 7), this being related to impairment of mood, ambulation, deep breathing and sleep, as well as more vertigo, nausea and tiredness (p < 0.001). Distraction, relaxation, mobilization, having conversations, patient-controlled analgesia (PCA) and pain monitoring were shown to be protective for severe pain (p < 0.001). Maximal pain in PCS and UCS was similar, but UCS obtained more analgesics (p < 0.001), and experienced more impairment of ambulation (p < 0.001) and deep breathing (p < 0.05). Severe pain has a major effect on daily-life activities and recovery after CS, and depends on modifiable factors. More effort is needed to improve the quality of care after CS.

Evaluation of levosimendan as treatment option in a large case-series of preterm infants with cardiac dysfunction and pulmonary hypertension.

Levosimendan as a calcium-sensitizer is a promising innovative therapeutical option for the treatment of severe cardiac dysfunction (CD) and pulmonary hypertension (PH) in preterm infants, but no data are available analyzing levosimendan in cohorts of preterm infants. The design/setting of the evaluation is in a large case-series of preterm infants with CD and PH. Data of all preterm infants (gestational age (GA) < 37 weeks) with levosimendan treatment and CD and/or PH in the echocardiographic assessment between 01/2018 and 06/2021 were screened for analysis. The primary clinical endpoint was defined as echocardiographic response to levosimendan. Preterm infants (105) were finally enrolled for further analysis. The preterm infants (48%) were classified as extremely low GA newborns (ELGANs, < 28 weeks of GA) and 73% as very low birth weight infants (< 1500 g, VLBW). The primary endpoint was reached in 71%, without difference regarding GA or BW. The incidence of moderate or severe PH decreased from baseline to follow-up (24 h) in about 30%, with a significant decrease in the responder group (p < 0.001). The incidence of left ventricular dysfunction and bi-ventricular dysfunction decreased significantly from baseline to follow-up (24 h) in the responder-group (p = 0.007, and p < 0.001, respectively). The arterial lactate level decreased significantly from baseline (4.7 mmol/l) to 12 h (3.6 mmol/l, p < 0.05), and 24 h (3.1 mmol/l, p < 0.01).  Conclusion: Levosimendan treatment is associated with an improvement of both CD and PH in preterm infants, with a stabilization of the mean arterial pressure during the treatment and a significant decrease of arterial lactate levels. Future prospective trials are highly warranted. What is Known: • Levosimendan as a calcium-sensitizer and inodilator is known to improve the low cardiac output syndrome (LCOS), and improves ventricular dysfunction, and PH, both in pediatric as well as in adult populations. Data related to critically ill neonates without major cardiac surgery and preterm infants are not available. What is New: • This study evaluated the effect of levosimendan on hemodynamics, clinical scores, echocardiographic severity parameters, and arterial lactate levels in a case-series of 105 preterm infants for the first time. Levosimendan treatment in preterm infants is associated with a rapid improvement of CD and PH, an increase of the mean arterial pressure, and a significant decrease in arterial lactate levels, as surrogate marker for a LCOS. • How this study might affect research, practice, or policy. As no data are available regarding the use of levosimendan in this population, our results hopefully animate the research community to conduct future prospective trails analyzing levosimendan in randomized controlled trials (RCT) and observational control studies. Additionally, our results potentially motivate clinicians to introduce levosimendan as second second-line therapy in cases of severe CD and PH in preterm infants without improvement using standard treatment strategies.

Prenatal ultrasound in fetuses with polycystic kidney appearance - expanding the diagnostic algorithm.

PURPOSE: Report on the diagnosis of prenatally detected fetal kidneys with bilateral polycystic appearance in a single center between 1999 and 2020 with special focus on renal morphology and biometry, amniotic fluid and extrarenal findings and proposal for an diagnostic algorithm. METHODS: Retrospective observational study including pregnancies with prenatally detected kidneys with bilateral polycystic appearance (n = 98). Cases and outcomes were compared according to prenatal findings with special focus on renal morphology, amount of amniotic fluid, and presence of extrarenal abnormalities. RESULTS: Most frequent diagnoses were autosomal recessive polycystic kidney disease (ARPKD, 53.1%), Meckel-Gruber syndrome (MKS, 17.3%) and autosomal dominant polycystic kidney disease (ADPKD, 8.2%). Other diagnoses included: Joubert-, Jeune-, McKusick-Kaufman- and Bardet-Biedl syndrome, overgrowth syndromes, Mainzer-Saldino syndrome and renal tubular dysgenesis. Renal abnormalities most frequently observed were hyperechogenic parenchyma, kidney enlargement, changes of corticomedullary differentiation and cystic changes of various degree. Oligo- and anhydramnios were mainly seen in ARPKD, RTD and second-trimester MKS. Extrarenal findings included skeletal (35.7%) and cardiac (34.7%) abnormalities as well as abnormalities of the central nervous system (27.6%). CONCLUSION: Gestational age at manifestation, kidney size, visibility of cysts, echogenicity, amniotic fluid volume, and the presence of associated extrarenal malformations allow to differentiate between the most frequent underlying diseases presenting with bilateral polycystic kidneys on prenatal ultrasound by following a diagnostic algorithm.

Uterine Artery Pseudoaneurysm after an Uncomplicated Vaginal Delivery: A Case Report.

Uterine artery pseudoaneurysm (UAP) is a rare and potentially life-threatening vascular anomaly caused by inadequate sealing of a ruptured wall of a uterine artery. It mainly occurs after a traumatic lesion and can lead to delayed postpartum hemorrhage. We report a rare case of UAP after an uncomplicated vaginal delivery in a patient with a history of deep-infiltrating endometriosis. Selective coil embolization was successfully performed. UAPs should always be considered in cases of unexplained abdominal pain after surgery or childbirth with or without vaginal bleeding.

Fetal ciliopathies: a retrospective observational single-center study.

PURPOSE: Report on the diagnosis of prenatally suspected multisystem ciliopathies in a single center between 2002 and 2020. METHODS: Retrospective observational single-center study including pregnancies with prenatal ultrasound features of multisystem ciliopathies, such as hyperechogenic kidneys together with polydactyly and/or other skeletal and extraskeletal findings. Cases were compared according to their prenatal findings and outcomes. RESULTS: 36 cases of multisystem ciliopathies were diagnosed. Meckel-Gruber syndrome (MKS) was the most common ciliopathy (n = 19/36, 52.8%), followed by disorders that belong to the group of short-rib thoracic dysplasia (SRTD, n = 10/36, 27.8%) McKusick-Kaufmann syndrome (MKKS, n = 4/36, 11.1%), Bardet-Biedl syndrome (BBS, n = 2/36, 5.5%) and Joubert syndrome (n = 1/36, 2.8%). All cases showed abnormalities of the kidneys, most often hyperechogenic parenchyma (n = 26/36, 72.2%), cystic dysplasia (n = 24/36, 66.7%), and/or bilateral kidney enlargement (n = 22/36, 61.1%). Oligohydramnios was mainly present in fetuses with MKS. Polydactyly (n = 18/36), abnormalities of the CNS (n = 25/36), and heart defects (n = 10/36) were associated in 50%, 69.4%, and 27.8%, respectively. CONCLUSION: Prenatal detection of renal abnormalities associated with skeletal or brain abnormalities should raise the suspicion for multisystem ciliopathies. Prenatal ultrasound can help to differentiate between different diseases and pave the way for subsequent targeted genetic testing.

DMBT1 amount in amniotic fluid depends on gestational age.

OBJECTIVE: Amniotic fluid is a mixture containing many different proteins as immunomodulatory peptides and growth factors. The glycoprotein Deleted in Malignant Brain Tumors 1 (DMBT1) is participated in innate immunity, angiogenesis and epithelial differentiation. We analyzed the DMBT1 concentration in amniotic fluid during gestation. METHODS: DMBT1 concentration was quantified by ELISA. Amniotic fluid samples were collected from preterm and term neonates. Effects of maternal or neonatal parameters were analyzed. To evaluate the source of DMBT1 we examined RNA of fetal tissue in relation to DMBT1 expression. RESULTS: The median DMBT1 concentration in amniotic fluid was 54.4 ng/ml. Amniotic fluid obtained <28 weeks of gestation revealed significantly lower DMBT1 concentrations compared to ≥28 weeks. We found a positive correlation between DMBT1 concentration and gestational age (p = .026). The fetal DMBT1 expression was pronounced in the gastrointestinal tract. CONCLUSIONS: The results showed that DMBT1 concentrations in amniotic fluid correlate with the gestational age during gestation and that the fetal gastrointestinal tract is a potential source of DMBT1. BRIEF RATIONALE: Amniotic fluid contains not only nutrients, but also many immunomodulatory peptides and growth factors. Deleted in Malignant Brain Tumors 1 (DMBT1) is an innate immunity protein with functions in epithelial differentiation and angiogenesis. The aim of this research was to study the DMBT1 content and the factors affecting its concentration in amniotic fluid during gestation. In summary, the results obtained in this study showed that DMBT1 is a component of amniotic fluid and that DMBT1 concentrations in amniotic fluid correlate with gestational age. In addition to this, the fetal gastrointestinal tract is a potential source of DMBT1 detected in amniotic fluid.

Outcome of Monochorionic Monoamniotic Twin Reversed Arterial Perfusion Sequence Diagnosed in the First Trimester.

INTRODUCTION: The aim of this study is to evaluate the outcome of pregnancies complicated by monochorionic monoamniotic twin reversed arterial perfusion sequence (MOMA TRAP) diagnosed in the first trimester. METHODS: All patients diagnosed with MOMA TRAP sequence <14.0 weeks of gestation in a 10-year study period were retrospectively analyzed for intrauterine course and outcome. All patients were offered either expectant management or intrauterine intervention. Adverse outcome was defined as either intrauterine death (IUD), neonatal death or preterm birth <34.0 weeks of gestation. RESULTS: In the study period, 17 cases with MOMA TRAP sequence were diagnosed. Of these, 2 couples opted for termination of pregnancy. The remaining 15 were divided into 2 groups depending on the management: group A (n = 8) with expectant management and group B (n = 7) with intrauterine intervention. All fetuses in group A died before 20 weeks. Survival in group B was significantly better with 4/7 (57.1%) life births at a median of 39.6 weeks of gestation (p = 0.0256). The reasons for IUD in the 3 cases in group B were hemodynamic, strangulation, and bleeding complications during intervention. CONCLUSIONS: Intrauterine intervention in MOMA TRAP pregnancies significantly improves neonatal survival, although it is still associated with a substantial risk for IUD by hemodynamic complications or entanglement.

Fetal teratomas - A retrospective observational single-center study.

OBJECTIVE: Evaluation of course and outcome of pregnancies with prenatally diagnosed fetal teratomas of various locations in a single center between 2002 and 2019. METHODS: Retrospective observational single-center study including prenatally suspected or diagnosed fetal teratomas. Focus was put on ultrasound findings during pregnancy. Complications, need for intervention and outcomes were compared according to tumor location. RESULTS: 79 cases of fetal teratomas were seen at our center between 2002 and 2019. Most frequent tumor locations were the sacrococcygeal region (59.5%), neck (20.2%) and oropharynx (7.6%). Complications mainly included polyhydramnios and cardiac compromise. Need for intervention during pregnancy was significantly higher in pericardial teratomas. Preterm birth before 37 and early preterm birth before 32 weeks occurred in 72.7% and 29.1%, respectively. Major causes of perinatal death were tumor bleeding in sacrococcygeal teratomas (SCTs) and respiratory failure in cervical and oropharyngeal teratomas. CONCLUSION: There is a high need for intervention in pregnancies complicated by fetal teratomas. Pericardiocentesis in pericardial teratomas is often inevitable to reduce the risk of intrauterine demise. Amniotic fluid drainage in associated severe polyhydramnios helps to reduce the risk of preterm birth, a major cause of additional morbidity and mortality. MRI in supplement to prenatal ultrasound is useful in fetal teratomas of the neck and oropharynx in order to plan delivery.

Obstetric and Neonatal Outcome of Pregnancy in Carney Complex: A Case Report.

Background: Carney complex (CNC) is a rare multiple endocrine neoplasia syndrome with autosomal dominant inheritance. Affected individuals present with mucocutaneous lentigines/blue nevi, cardiac and noncardiac myxomatous tumors, and multiple endocrine tumors. Mutations in PRKAR1A have been identified as genetic cause of the disease. Here, we report on pregnancy, delivery and puerperium in a woman with genetically confirmed CNC and her newborn. Case: The 31 year-old gravida 5 para 1 with CNC was referred at 26 weeks of gestation. Adrenocorticotropin-independent hypercortisolism, hyperglycemia, hypertension, low serum potassium, and osteoporotic fractures were present. Treatment with metyrapone, a reversible 11-beta-hydroxylase inhibitor, was initiated. The maternal condition improved, and a 5 weeks' pregnancy prolongation could be achieved. Elective repeat cesarean section was performed at 31 weeks of gestation for recurrent vaginal bleeding. The neonate developed transient hyponatremia necessitating hydrocortisone substitution for 2 weeks. Conclusion: In our case, treatment of CNC-associated hypercortisolism in pregnancy with metyrapone was effective. Maternal side effects did not occur. The newborn presented with transient hypocortisolism most likely due to transplacental drug effect. Our case illustrates that the treatment of rare diseases in pregnancy represents a challenge requiring interdisciplinary team work.

Prenatal diagnosis, associated findings and postnatal outcome of fetuses with double outlet right ventricle (DORV) in a single center.

Objective To assess the spectrum of associated anomalies, the intrauterine course, postnatal outcome and management of fetuses with double outlet right ventricle (DORV). Methods All cases of DORV diagnosed prenatally over a period of 8 years were retrospectively collected in a single tertiary referral center. All additional prenatal findings were assessed and correlated with the outcome. The accuracy of prenatal diagnosis was assessed. Results Forty-six cases of DORV were diagnosed prenatally. The mean gestational age at first diagnosis was 21+4 weeks (range, 13-37). A correct prenatal diagnosis of DORV was made in 96.3% of the cases. If the relation of the great arteries, the position of the ventricular septal defect (VSD) and additional cardiac anomalies are taken into account, the prenatal diagnosis was correct in 92.6% of the cases. One case was postnatally classified as transposition of the great arteries with subpulmonary VSD and was excluded from further analysis. A total of 41 (91.1%) fetuses with DORV had major additional cardiac anomalies, 30 (66.7%) had extracardiac anomalies and 13 (28.9%) had chromosomal or syndromal anomalies. Due to their complex additional anomalies, five (11.1%) of our 45 fetuses had multiple malformations and were highly suspicious for non-chromosomal genetic syndromes, although molecular diagnosis could not be provided. Disorders of laterality occurred in 10 (22.2%) fetuses. There were 17 terminations of pregnancy (37.8%), two (4.4%) intrauterine and seven (15.6%) postnatal deaths. Nineteen of 22 (86.4%) live-born children with an intention to treat were alive at last follow-up. The mean follow-up among survivors was 32 months (range, 2-72). Of 21 children who had already undergone postnatal surgery, eight (38.1%) achieved biventricular repair and 13 (61.9%) received univentricular palliation. One recently born child is still waiting for surgery. All children predicted prenatally to need a single ventricle palliation, and all children predicted to achieve biventricular repair, ultimately received the predicted type of surgery. After surgery, 14 of 18 (77.8%) children were healthy without any impairment. Conclusion DORV is a rare and often complex cardiac anomaly that can be diagnosed prenatally with high precision. DORV is frequently associated with major additional anomalies, leading to a high intrauterine and postnatal loss rate due to terminations or declined postnatal therapy. Without additional anomalies, the prognosis is good, although approximately 60% of children will have single ventricle palliation.

Outcome of Bronchopulmonary Sequestration with Massive Pleural Effusion after Intrafetal Vascular Laser Ablation.

OBJECTIVE: To assess the outcome of 12 fetuses with bronchopulmonary sequestration (BPS) and massive pleural effusion after intrafetal vascular laser ablation (VLA). METHODS: All fetuses with BPS and massive pleural effusion that were treated with intrafetal VLA during a 5-year period (2012-2016) were reviewed for safety, intrauterine course, and postnatal outcome. RESULTS: In the study period, 12 fetuses with BPS were treated with VLA. In 7 (58.3%) fetuses, complete cessation of blood flow was achieved after the first VLA, while in 5 (41.7%) fetuses, residual perfusion of the feeding vessel was demonstrated at follow-up. A second intervention was successful in 4 of 5 (80%) fetuses. Overall, in 11 of 12 (91.7%) fetuses, complete coagulation of the feeding vessel could be achieved, followed by a reduction in size or complete resolution of the BPS. All 11 fetuses with successful prenatal intervention were live-born at a median gestational age of 39+1 (range, 37+5-41+2) weeks. Postnatally, 2 (18.2%) of the 11 newborns underwent sequestrectomy, as well as the preterm newborn on which a second fetal intervention was not feasible. CONCLUSION: VLA is an effective and safe treatment of BPS that appears to be of benefit in improving prognosis and decreasing the need for postnatal sequestrectomy.

Kidney Na+,K(+)-ATPase is associated with moesin.

Na+,K(+)-ATPase is a ubiquitous plasmalemmal membrane protein essential for generation and maintenance of transmembrane Na+ and K+ gradients in virtually all animal cell types. Activity and polarized distribution of renal Na+,(+)-ATPase appears to depend on connection of ankyrin to the spectrin-based membrane cytoskeleton as well as on association with actin filaments. In a previous study we showed copurification and codistribution of renal Na+,K(+)-ATPase not only with ankyrin, spectrin and actin, but also with two further peripheral membrane proteins, pasin 1 and pasin 2. In this paper we show by sequence analysis through mass spectrometry as well as by immunoblotting that pasin 2 is identical to moesin, a member of the FERM (protein 4.1, ezrin, radixin, moesin) protein family, all members of which have been shown to serve as cytoskeletal adaptor molecules. Moreover, we show that recombinant full-length moesin as well as its FERM domain bind to Na+,K(+)-ATPase and that this binding can be inhibited by an antibody specific for the ATPase activity-containing cytoplasmic loop (domain 3) of the Na+,K(+)-ATPase alpha-subunit. This loop has been previously shown to be a site essential for ankyrin binding. These observations indicate that moesin might not only serve as direct linker molecule of Na+,K(+)-ATPase to actin filaments but also modify ankyrin binding at domain 3 of Na+,K(+)-ATPase in a way similar to protein 4.1 modifying the binding of ankyrin to the cytoplasmic domain of the erythrocyte anion exchanger (AE1).