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.

Intussusception in children: lessons learned from intestinal lymphoma as a rare lead-point.

BACKGROUND: Most cases of intussusception in children are idiopathic. Rarely, a malignant disease such as intestinal lymphoma may cause intussusception. Due to dramatic changes of expected outcome with chemotherapy regime alone, the surgical management of patients with intestinal lymphoma presenting with intussusception has to be reevaluated. METHODS: Retrospective chart review from May 2011 to February 2017. We included all patients with intestinal lymphoma presenting with intussusception. RESULTS: We found five patients with a mean age of 6.4 years (range 3-16). The most common presenting symptom was abdominal pain for several weeks which had acutely worsened. In all but one patient an ultrasound before pneumatic or hydrostatic reduction showed a finding suspicious of a pathological lead-point. Pneumatic or hydrostatic reduction was attempted in all patients, no complications were noted. In one patient reduction was not successful. Recurrence after reduction occurred in two patients. Two patients needed surgery, three had a percutaneous ultrasound-guided biopsy for diagnostic purposes. All patients had aggressive mature B cell non-Hodgkin lymphoma. CONCLUSION: A high index of suspicion for the presence of a pathological lead-point in children older than 4 years and children with recurrent intussusception is necessary in patients presenting with intussusception. Malignant, highly aggressive B cell non-Hodgkin lymphoma, although rare, must actively be searched for. Pneumatic or hydrostatic reduction should remain the first line treatment in most cases.

Intestinal IMINO transporter SIT1 is not expressed in human newborns.

The expression of amino acid transporters in small intestine epithelia of human newborns has not been studied yet. It is further not known whether the maturation of imino acid (proline) transport is delayed as in the kidney proximal tubule. The possibility to obtain small intestinal tissue from patients undergoing surgery for jejunal or ileal atresia during their first days after birth was used to address these questions. As control, adult terminal ileum tissue was sampled during routine endoscopies. Gene expression of luminal imino and amino acid transporter SIT1 (SLC6A20) was approximately threefold lower in newborns versus adults. mRNA levels of all other luminal and basolateral amino acid transporters and accessory proteins tested were similar in newborn mucosa compared with adults. At the protein level, the major luminal neutral amino acid transporter B0AT1 (SLC6A19) and its accessory protein angiotensin-converting enzyme 2 were shown by immunofluorescence to be expressed similarly in newborns and in adults. SIT1 protein was not detectable in the small intestine of human newborns, in contrast to adults. The morphology of newborn intestinal mucosa proximal and distal to the obstruction was generally normal, but a decreased proliferation rate was visualized distally of the atresia by lower levels of the mitosis marker Ki-67. The mRNA level of the 13 tested amino acid transporters and accessory proteins was nonetheless similar, suggesting that the intestinal obstruction and interruption of amniotic fluid passage through the small intestinal lumen did not affect amino acid transporter expression. NEW & NOTEWORTHY System IMINO transporter SIT1 is not expressed in the small intestine of human newborns. This new finding resembles the situation in the proximal kidney tubule leading to iminoglycinuria. Lack of amniotic fluid passage in small intestinal atresia does not affect amino acid transporter expression distal to intestinal occlusion.

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.

Early mobilization after flexor tendon repair in children.

PURPOSE: Aim of the study was to provide an age-adapted rehabilitation protocol for flexor tendon repairs of children and to evaluate a patient series accordingly. METHODS: A modified Kessler's technique was used to repair 49 flexor tendon injuries in 39 children. All children had immediate postoperative mobilization according to the protocol that provides specific guidelines for preschoolers, children and teenagers. Range of motion was monitored and the final results were evaluated retrospectively. RESULTS: All children could be treated successfully according to the protocol with no occurrence of secondary tendon ruptures. Forty finger injuries were evaluated according to the Strickland classification, resulting in a median total active motion of 92.6 % with 29 (72.5 %) excellent results, 8 (20 %) good results, 3 (7.5 %) fair results and no poor result. All 7 thumbs had an excellent result according to the Buck-Gramcko score. There was no significant difference in outcomes between the three age groups. CONCLUSIONS: The rehabilitation protocol provided in this study allows an age-adapted early mobilization of children's hands after flexor tendon injuries. It respects age-specific limitations in rehabilitation and takes a child's superior healing capacity compared to adults into account. The good results and the very low complication rate observed in the present series suggest that the extra effort of early mobilization may be justified.

Microscopic wire guide-based orotracheal mouse intubation: description, evaluation and comparison with transillumination.

Airway access is needed for a number of experimental animal models, and the majority of animal research is based on mouse models. Anatomical conditions in mice are small, and the narrow glottic opening allows intubation only with a subtle technique. We therefore developed a microscopic endotracheal intubation method with a wire guide technique in mice anaesthetized with halothane in oxygen. The mouse is hung perpendicularly with its incisors on a thread fixed on a vertical plate. The tongue is placed with a pair of forceps between the left hand's thumb and forefinger and slightly pulled, while the neck and thorax are positioned using the third and fourth fingers. By doing so, the neck can be slightly stretched, which allows optimal visualization of the larynx and the vocal cords. To ensure a safe intubation, a fine wire guide is placed under vision between the vocal cords and advanced about 5 mm into the trachea. An intravenous 22G x 1 in. plastic or Teflon catheter is guided over this wire. In a series of 41 mice, between 21 and 38 g, the success rate for the first intubation attempt was >95%. Certainty of the judgement procedure was 100% and success rate was higher using the described method when compared with a transillumination method in a further series. The technique is safe, less invasive than tracheostomy and suitable for controlled ventilation and pulmonary substance application.

[Conventional radiological examination of the nasal bone--helpful or superfluous? Case histories and literature survey]. / Die konventionelle radiologische Nasenbeinaufnahme--sinnvoll oder überflüssig? Fallvorstellungen mit Literaturübersicht.

Fractures of the nasal pyramid are among the most common injuries to the skull. Numerous studies have shown that conventional radiological examination of simple fractures of the nose give no information that is helpful either in reaching a diagnosis or in deciding on the therapeutic management. Nevertheless, physicians still frequently refer patients for such examinations to check for fractures. It is now increasingly important to reduce the costs, and particularly to avoid unhelpful investigations and unnecessary radiation exposure.

Impact of carbon dioxide versus air pneumoperitoneum on peritoneal cell migration and cell fate.

BACKGROUND: Postoperative systemic immune function is suppressed after open abdominal surgery, as compared with that after minimally invasive abdominal surgery. As a first line of defense, peritoneal macrophages (PMo) and polymorphonuclear neutrophil granulocytes (PMNs) are of primary importance in protecting the body from microorganisms. Previous studies have shown changes in these cell populations over time after open versus laparoscopic surgery. This study aimed to investigate the dynamics of cell recruitment and clearance of peritoneal cells. METHODS: Female NMRI mice (33 +/- 2 g) were randomly assigned to carbon dioxide (CO2) or air insufflation. Intravasal cells with phagocytic capabilities were selectively stained by intravenous injection of the fluorescent dye PKH26 24 h before surgery. Gas was insufflated into the peritoneal cavity through a catheter, and the pneumoperitoneum was maintained for 30 min. Peritoneal lavage was performed 1, 3, 8, or 24 h after surgery. Apoptotic cells were assessed by flow cytometry using a general caspase substrate. RESULTS: The total peritoneal cell count did not differ between groups. The PKH26-positive PMo level was significantly increased after CO2, as compared with air, at 1 h and 24 h. The ratio of apoptotic PMo did not differ between the groups. In the peritoneal lavage, polymorphonuclear leukocytes (PMNs) were tripled in the air group, as compared with the CO2 group, whereas the ratio of apoptotic PMNs was significantly decreased. There was a higher fraction of PKH26-positive PMNs after air exposure, as compared with that after CO2. CONCLUSIONS: Air exposure triggered a higher transmigration rate of PMNs from the blood compartment into the peritoneal cavity and decreased PMN apoptosis, as compared with CO2. The lower proportion of PKH26-positive peritoneal macrophages in the air group might have been attributable to a higher inflammatory stimulation than in the CO2 group, leading to increased emigration of PMo to draining lymph nodes. All the findings underscore a complex cell-specific regulation of cell recruitment and clearance in the peritoneal compartment.

Early peritoneal macrophage function after laparoscopic surgery compared with laparotomy in a mouse mode.

BACKGROUND: The authors previously demonstrated postoperative preservation of the immune function measured by delayed-type skin reaction and tumor growth after laparoscopic surgery, as compared with laparotomy. For further elucidation of the origin of the demonstrated immune preservation, peritoneal macrophage (PMo) function was investigated 1 h after different surgical procedures. METHODS: Female NMRI mice were divided into five groups: anesthesia only, abdominal skin incision, laparotomy, peritoneal carbon dioxide (CO2) insufflation, and peritoneal air insufflation. Escherichia Coli phagocytosis, tumor necrosis factor-alpha (TNF-alpha), transforming growth factor-beta1 (TGF-beta1), and interleukin-10 (IL-10) release of isolated PMo were investigated. RESULTS: All invasive interventions reduced the PMo phagocytosis by factors of approximately 2 to 4.7, as compared with the sham control group. Spontaneous ex vivo TNF-alpha release was significantly increased whenever the abdominal cavity was exposed to ambient air. The macrophage's ability to release TNF-alpha after E. coli exposure was diminished in the abdominal air exposure groups, as compared with the CO2 insufflation group. CONCLUSION: Reduced phagocytosis 1 h after surgical interventions suggests a contribution of PMo to the altered immune function. When exposed to CO2, PMo show a decreased basal TNF-alpha release. However, PMo also show an increased TNF-alpha release after a second immune stimulation (E. coli), suggesting a greater competency of interaction in an immune defense reaction after CO2 exposure.

Tissue endothelin-converting enzyme activity correlates with cardiovascular risk factors in coronary artery disease.

BACKGROUND: Endothelin-converting enzymes (ECEs) are the key enzymes in endothelin-1 (ET-1) generation. However, their pathophysiological role in patients with cardiovascular disease remains elusive. METHODS AND RESULTS: Vascular reactivity to big endothelin-1 (bigET-1; 10(-9) to 10(-7) mol/L) and ET-1 (10(-9) to 10(-7) mol/L) were examined in the internal mammary artery (IMA, n=33) and saphenous vein (SV, n=27) of patients with coronary artery disease with identified cardiovascular risk factors. Vascular ECE activity was determined by conversion of exogenously added bigET-1 to ET-1. Tissue contents of bigET-1 and ET-1 were measured by radioimmunoassay. In addition, the effects of LDL and oxidized LDL on ECE-1 protein levels were determined by Western blot analysis in human IMA endothelial cells. In the IMA, vascular ECE activity showed an inverse correlation with serum LDL levels (r=-0.76; P<0.01) and systolic and diastolic blood pressure and a positive correlation with fibrinogen (r=0.58; P<0.05). In the SV, fibrinogen was the only parameter to be correlated with vascular ECE activity. Vascular tissue content of bigET-1 was attenuated in the IMA of patients with hyperfibrinogenemia but increased in patients with elevated systolic blood pressure and increased serum LDL levels (P<0.05). Most interestingly, LDL and oxidized LDL downregulated ECE-1 protein levels in human IMA endothelial cells (P<0.05). CONCLUSIONS: These data demonstrate, for the first time, that vascular ECE activity is (1) inversely correlated with serum LDL levels and blood pressure and (2) positively associated with fibrinogen in human vascular tissue. Hence, ECE-1 activity may modulate cardiovascular risk in patients with coronary artery disease.

Abdominal pulsatile tumor after endovascular abdominal aortic aneurysm repair.

A 70 years old patient was successfully treated for infrarenal aortic aneurysm by an endovascular bifurcated prosthesis. Three months later, because of dysuria, he underwent urological examination revealing an abdominal pulsatile tumor. Thereafter, the patient was sent to our emergency ward with suspected symptomatical endoleak. Radiological screening by computer tomography and magnetic resonance angiography showed good post-operative results without endoleak. Patient was treated with antispasmodic medication and is doing well today. Because endovascular repair of aortic aneurysm, in contrast to an open approach, does not eliminate the aneurysm itself, post-operative abdominal palpation can be ambiguous. Magnetic resonance angiography--without the need of nephrotoxic contrast medium--compares favourably to CT and provides excellent pictures with less artefacts for post-operative screening of endoleak. If reperfusion can be excluded, pulsation is due to the transmission of the blood-pressure wave to the thrombosed aneurysm.