Dexterous helical magnetic robot for improved endovascular access.

Treating vascular diseases in the brain requires access to the affected region inside the body. This is usually accomplished through a minimally invasive technique that involves the use of long, thin devices, such as wires and tubes, that are manually maneuvered by a clinician within the bloodstream. By pushing, pulling, and twisting, these devices are navigated through the tortuous pathways of the blood vessels. The outcome of the procedure heavily relies on the clinician's skill and the device's ability to navigate to the affected target region in the bloodstream, which is often inhibited by tortuous blood vessels. Sharp turns require high flexibility, but this flexibility inhibits translation of proximal insertion to distal tip advancement. We present a highly dexterous, magnetically steered continuum robot that overcomes pushability limitations through rotation. A helical protrusion on the device's surface engages with the vessel wall and translates rotation to forward motion at every point of contact. An articulating magnetic tip allows for active steerability, enabling navigation from the aortic arch to millimeter-sized arteries of the brain. The effectiveness of the magnetic continuum robot has been demonstrated through successful navigation in models of the human vasculature and in blood vessels of a live pig.

Impact on postoperative, neonatal and 2-year neurodevelopmental outcomes of UA-AREDF during and after fetal spina bifida repair.

OBJECTIVE: Absent or reversed end-diastolic flow (AREDF) in the umbilical artery (UA) on Doppler is a known phenomenon during fetal interventions, such as fetal open spina bifida (OSB) repair. We aimed to evaluate the clinical importance of these Doppler findings by investigating the impact of UA-AREDF on postoperative, neonatal and 2-year neurodevelopmental outcomes. METHODS: This was a prospective study of pregnancies undergoing fetal OSB repair at the Zurich Center for Fetal Diagnosis and Therapy between 2010 and 2019. The group with UA-AREDF during or immediately after the intervention was compared to the group with normal UA Doppler. Primary endpoint was the FIGO scores of cardiotocography (CTG) 1, 2 and 6 h postoperatively and on day 1 after surgery. Secondary endpoints were the neonatal parameters and 2-year neurodevelopmental outcome assessed using the Bayley Scales of Infant and Toddler Development, Third Edition. RESULTS: Data of 130 patients were analyzed. None of the fetuses had UA-AREDF before OSB repair. Normal UA Doppler was observed in 107 (82%) patients and UA-AREDF was observed in 23 (18%) during or immediately after OSB surgery. UA-AREDF was more often observed after version of the fetus (P = 0.045). Seventeen (13%) cases had absent end-diastolic flow (UA-AEDF) and six (5%) cases had reversed end-diastolic flow (UA-REDF). UA-AREDF disappeared in all 23 cases within the first day after OSB surgery. One-third of all CTGs were restricted in oscillation after surgery, but no significant difference in CTG 1, 2 and 6 h postoperatively or on the first postoperative day was found between the UA-AREDF and normal-Doppler groups (P > 0.05). Gestational age at delivery, UA pH, 5-min Apgar score and birth weight were comparable between the two groups, and there was no difference in the 2-year neurodevelopmental outcome (P > 0.05). The neonatal and 2-year neurodevelopmental outcomes also did not differ significantly between the UA-REDF and UA-AEDF groups. CONCLUSIONS: Postoperative CTG abnormalities occur and recover at a similar rate in fetuses with transitory UA-AREDF and those with normal Doppler during fetal OSB repair. UA-AREDF during fetal OSB repair did not negatively influence postnatal or 2-year neurodevelopmental outcomes. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Association of uterine activity and maternal volatile anesthetic exposure during open fetal surgery for spina bifida: a retrospective analysis.

BACKGROUND: Recent warnings postulate a possible damaging effect of volatile anesthetics on the fetus. In our archive of fetal surgeries, we found wide variation in dosing of volatile anesthetics during spina bifida surgeries. We hypothesized that there was an association between volatile anesthetic exposure and uterine activity. METHODS: Sixty anesthesia records from spina bifida operations were assessed. We analyzed the course of the administered volatile anesthetic during surgery and calculated from each patient's anesthesia record the volatile anesthetic exposure expressed in vol%h. We divided the records into two post hoc groups of the 20 lowest exposure (Group L) versus the 20 highest exposure (Group H), and compared them for uterine activity and fetal heart rate. RESULTS: The number of contractions per hour was significantly greater in Group H (mean 1.3, SD ±â€¯1.2) compared with Group L (mean 0.5, SD ±â€¯0.6, P=0.049). There was no difference between the groups for the administration of the tocolytic drug atosiban (P=0.29). The course of the mean arterial pressure did not significantly differ but group H needed significantly more vasoactive medication (P <0.05). CONCLUSIONS: We found that a lower intra-operative volatile anesthetic exposure than recommended in the MOMS-trial (i.e. <2.0 minimum alveolar concentration [MAC]) was not associated with an increase in intra-operative uterine activity. This is an indication that during spina bifida surgery, 2.0 MAC may not be necessary to avoid potentially harmful uterine activity.

Systematic classification of maternal and fetal intervention-related complications following open fetal myelomeningocele repair - results from a large prospective cohort.

OBJECTIVE: To systematically categorise all maternal and fetal intervention-related complications after open fetal myelomeningocele (fMMC) repair of the first 124 cases operated at the Zurich Centre for Fetal Diagnosis and Therapy. DESIGN: A prospective cohort study. SETTING: Single centre. POPULATION: Mothers and fetuses after fMMC repair. METHODS: Between 2010 and 2019, we collected and entered all maternal complications following fMMC repair into the Clavien-Dindo classification. For fetal complications, a classification system based on the Medical Dictionary for Regulatory Activities terminology of Adverse Events was used including the preterm definitions of the World Health Organization. MAIN OUTCOME MEASURES: Systematic classification of maternal and fetal complications following fMMC repair. RESULTS: Gestational ages at surgery and birth were 25.0 ± 0.8 and 35.4 ± 2.0 weeks, respectively. In 17% of all cases, no maternal complications occurred. Maternal intervention-related complications were observed as follows: 69% grade 1, 36% grade 2, 25% grade 3, 6% grade 4 and 0% grade 5. In 34%, no fetal complications were noted; however, 43% of the fetuses developed a grade 1, 14% a grade 2, 8% a grade 3, 2% a grade 4 and 2% a grade 5 complication. CONCLUSION: This study raises awareness of complications following open fMMC repair; 6% of mothers and 2% of fetuses experienced a severe complication (grade 4) and perinatal death rate of 2% was observed (grade 5). These data are useful for prenatal counselling, they help to improve the system of fetal surgical care, and they allow benchmarking with other centres as well as comparison with fetoscopic approaches. TWEETABLE ABSTRACT: Systematic classification of all maternal and fetal intervention-related complications following open fMMC repair.

Experimental tissue engineering of fetal skin.

PURPOSE: In some human fetuses undergoing prenatal spina bifida repair, the skin defect is too large for primary closure. The aim of this study was to engineer an autologous fetal skin analogue suitable for in utero skin reconstruction during spina bifida repair. METHODS: Keratinocytes (KC) and fibroblasts (FB) isolated from skin biopsies of 90-day-old sheep fetuses were cultured. Thereafter, plastically compressed collagen hydrogels and fibrin gels containing FB were prepared. KC were seeded onto these dermal constructs and allowed to proliferate using different culture media. Constructs were analyzed histologically and by immunohistochemistry and compared to normal ovine fetal skin. RESULTS: Development of a stratified epidermis covering the entire surface of the collagen gel was observed. The number of KC layers and degree of organization was dependent on the cell culture media used. The collagen hydrogels exhibited a strong tendency to shrink after eight to ten days of culture in vitro. On fibrin gels, we did not observe the formation of a physiologically organized epidermis. CONCLUSION: Collagen-gel-based ovine fetal cell-derived skin analogues with near normal anatomy can be engineered in vitro and may be suitable for autologous fetal transplantation.

A comparative study on culture conditions and routine expansion of amniotic fluid-derived mesenchymal progenitor cells.

BACKGROUND: Amniotic fluid (AF) cell populations will be applied in perinatology. We aimed to test the feasibility of large-scale cell expansion. STUDY METHODS: We determined the best out of three published expansion protocols for mesenchymal progenitors (AF samples, n = 4) in terms of self-renewal ability. Characterization was performed based on morphology, surface marker analysis, cytogenetic stability, and differentiation potential. The conditions for the best self-renewal ability were further determined in a consecutive series (n = 159). RESULTS: The medium containing fetal bovine serum (FBS), epidermal growth factor, insulin, transferrin, and tri-iodothyronine, combined with seeding on gelatin-coated wells, best stimulated the growth of cells with mesenchymal features, as demonstrated by flow cytometry; however, only osteogenic differentiation was possible. Large-scale testing (n = 44) failed to confirm a robust self-renewal ability. Better results were obtained (n = 88) using optimized FBS or an increased initial cell density. Eventually over 81% of cultures continued growing after the initial medium change and had mesenchymal features but failed differentiation assays. DISCUSSION: Routine in vitro expansion of AF-derived mesenchymal cells remains problematic. Despite an increase in successful cell cultures from 40 up to 80% using optimized serum and an increased cell density, eventually cells failed to demonstrate differentiation abilities. Routine isolation and expansion from unselected AF samples remains a challenge.

Fetal mesenchymal stem cells: isolation, properties and potential use in perinatology and regenerative medicine.

The fetus is a source of nonembryonic stem cells (SC), with potential applications in perinatal medicine. Cells derived from the placenta, membranes, amniotic fluid or fetal tissues are higher in number, expansion potential and differentiation abilities compared with SC from adult tissues. Although some obstacles keep SC biology at distance from clinical application, the feasibility of using (homologous) SC for tissue engineering for the fetus with a congenital birth defect has been demonstrated. Also, other pathologies may benefit from SC technology.

Changes in olfactory function with several pregnancies?

OBJECTIVE: To investigate whether olfactory performance decreases as a function of the number of pregnancies, previous research having indicated that olfactory function decreases in the course of pregnancy. METHODS: In a prospective study three groups of women were investigated (total n = 93), women who have given birth to no children (group 0), to one child (group 1), and to two or three children (group 2). Olfactory function was assessed using the "Sniffin' Sticks" kit. RESULTS: There was no significant difference in olfactory function between the three groups. CONCLUSION: While pregnancy is typically accompanied by changes in olfactory performance, these alterations obviously do not translate into a long-lasting change in olfactory function dependent on the number of pregnancies.

Changes in olfactory function in pregnancy and postpartum.

OBJECTIVE: To track changes in olfactory performance during pregnancy and the postpartum. METHODS: In a prospective study the olfactory function of 38 pregnant women was assessed at about 12, 21, and 36 weeks of pregnancy and 7 weeks after delivery. A control group of 46 nonpregnant women were also asked to rate the intensity and hedonic tone of 10 "natural" odors. RESULTS: There was no difference in olfactory performance between the women in the first trimester of pregnancy and the controls, but at approximately 36 weeks of pregnancy the pregnant women experienced a decreased odor threshold compared with the nonpregnant controls, and this decrease was still present after delivery. There was no significant difference between the groups in capacity for odor discrimination or odor identification. "Objective" decreases were observed even though pregnant women rated their olfactory sensitivity significantly higher than the controls. Although the 2 groups did not differ with regard to intensity ratings of the 10 "natural" odors, there were differences with regard to the hedonic ratings. CONCLUSION: Pregnancy is accompanied by changes in olfactory performance. Changes in hedonic odor ratings indicate a potential embryo-protective mechanism. The discrepancy between "objective" and "subjective" olfactory function may relate to changes in the cognitive processing of chemosensory information during pregnancy.

Manufacture of a cell-free amnion matrix scaffold that supports amnion cell outgrowth in vitro.

We manufactured a cell-free extracellular matrix scaffolds in order to obtain a support material for amnion cell outgrowth, eventually being used for repair of prematurely ruptured fetal membrane. Human preterm or term amnion tissue was separated into its collagenous extracellular matrix and cell components. The acellular scaffold was explored for its capacity to support regrowth of isolated human amnion epithelial or mesenchymal cells in vitro. The outgrowth of amnion cells on and in the scaffold was investigated by scanning and transmission electron microscopy, and confocal laser scanning microscopy. Cell-free amnion matrix scaffolds demonstrated a porous collagen fiber network similar as in native amnion. Inoculation of acellular amnion scaffolds with human amnion cells revealed that its property to support amnion cell outgrowth was retained. Amnion epithelial and mesenchymal cells were found to grow into dense layers on the surface of the scaffold within 3-4 days and 7-8 days, respectively, and to some extent, invaded the scaffold during the culture period. Manufactured acellular amnion matrix retains structural and functional properties required for cell outgrowth in vitro. It may become useful to repair prematurely ruptured fetal membranes.

Cross sectional study of automated blood pressure measurements throughout pregnancy.

OBJECTIVE: To generate reliable new reference ranges for pregnancy blood pressure from a large population. DESIGN: A prospective cross sectional study. SETTING: Obstetric outpatient clinic, Zurich University Hospital. SAMPLE: Accurately dateable singleton pregnancies (Caucasian: n= 3234; Asian [predominantly from Sri Lanka, Thailand and the Philippines]: n= 577; Black n= 212). METHODS: Between January 1996 and February 2000 blood pressure was determined in 4023 pregnant women using an oscillometric automated device (Dinamap) according to British Hypertension Society recommendations. Women receiving antihypertensive medication were excluded. MAIN OUTCOME MEASURE: Blood pressure. RESULTS: Only the means of duplicate measures at the booking visit (5-42 weeks) were used in the analysis. Mean blood pressure decreased from early to mid pregnancy before increasing to levels 4 mmHg higher at term than in early pregnancy. Values >130/80 and <90/50 mmHg were above the 95th and below the 5th centiles, respectively. Parity, age and body mass index were significant determinants in Caucasians. Blood pressure was slightly lower in Asians and Blacks. CONCLUSIONS: The current World Health Organisation definition of high diastolic blood pressure (>or=90 mmHg on two occasions) reflects values >2 standard deviations from the mean. This may be too conservative as threshold for detecting women at risk of pre-eclampsia. Further studies are required to determine the prognostic implications of gestational values >or=95th centile (>or=130/80 mmHg) and