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INTRODUCTION: Chorioamniotic membrane separation (CMS) is a known complication after fetal spina bifida (fSB) repair. This study's goal was to analyze women's outcomes with open fSB repair and CMS (group A) compared to the ones without (group B) and to assess the influence of CMS size and patient management. METHODS: 194 women with open fSB repair at our center were included in this retrospective study. Outcomes of group A were compared to the ones of group B. Regression analysis was performed to assess risk factors for CMS. Two subgroup analyses assessed the impact of CMS size (local (A-local) vs. global (A-global)) as well as patient management (A1 = hospitalization vs. A2= no hospitalization) on pregnancy outcomes. RESULTS: Of 194 women, 23 (11.9%) were in group A, and 171 (88.1%) in group B. Preterm premature rupture of membranes (PPROM) (69.6% vs. 24.1%, p = <0.001), amniotic infection syndrome (AIS) (22.7% vs. 7.1%, p = 0.03), histologically confirmed chorioamnionitis (hCA) (40.0% vs. 14.7%, p = 0.03), length of hospital stay (LOS) after fSB repair (35 (19-65) vs. 17 (14-27) days), and overall LOS (43 (33-71) vs. 35 (27-46) days, p = 0.004) were significantly more often/longer in group A. Gestational age (GA) at delivery was significantly lower in group A compared to group B (35.3 (32.3-36.3) vs. 36.7 (34.9-37.0) weeks, p = 0.006). Regression analysis did not identify risk factors for CMS. Subgroup analysis comparing CMS sized in group A-local vs. A global showed: higher AIS rate (42% vs. 0%, p = 0.04), lower LOS (22.0 (15.5-42.5) vs. 59.6 ± 24.1, p = 0.003). Comparison of group A1 vs. A2 showed: longer LOS (49.3 ± 22.8 vs. 15 (15-17.5) days, p <0.001), lower planned readmission rate (5.6% vs. 80%, p = 0.003). CONCLUSION: CMS significantly increased the risk of PPROM, AIS, hCA, caused longer LOS, and lower GA at delivery. Women with local CMS had higher AIS rates but shorter LOS compared to women with global CMS, while apart from LOS pregnancy outcomes did not differ regarding patient management (hospitalization after CMS yes vs. no).
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PURPOSE: Rectal suction biopsy (RSB) is the gold standard for diagnosing Hirschsprung's disease (HD) in infants. Despite being a common procedure, no standard exists on the number of biopsy specimens and their respective level within the rectum. METHODS: We conducted a retrospective review of epidemiological and pathological data of patients who underwent RSB at our institution between January 2011 and May 2022. During RSB we obtain 4 specimens: at 1 cm, 3 cm and 5 cm above the dentate line, besides one specimen at the dentate line. We used a logistic regression model for statistical analysis and included control variables (e.g. underlying disease, weight at first biopsy, gestational age). RESULTS: A total of 92 patients underwent 115 biopsies, with an average of 3.77 specimens per session. Of the specimens taken at 1 cm above the dentate line 73.9% were conclusive, at 3 cm 75.9% and at 5 cm 79.2%. Specimens taken at the dentate line were squamous or transitional epithelia in 31.5% and therefore of no use for HD diagnostics. The specimen at 3 cm shows the highest discriminative power whether the biopsy session was diagnostic (p-value < 1%). CONCLUSIONS: We propose that a total of three specimens, namely one at 1 cm, one at 3 cm and one at 5 cm above the dentate line, is enough to diagnose or exclude HD.
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Enfermedad de Hirschsprung , Recto , Humanos , Enfermedad de Hirschsprung/patología , Enfermedad de Hirschsprung/diagnóstico , Estudios Retrospectivos , Recto/patología , Femenino , Succión , Masculino , Biopsia/métodos , Lactante , Recién NacidoRESUMEN
A major obstacle in applying machine learning for medical fields is the disparity between the data distribution of the training images and the data encountered in clinics. This phenomenon can be explained by inconsistent acquisition techniques and large variations across the patient spectrum. The result is poor translation of the trained models to the clinic, which limits their implementation in medical practice. Patient-specific trained networks could provide a potential solution. Although patient-specific approaches are usually infeasible because of the expenses associated with on-the-fly labeling, the use of generative adversarial networks enables this approach. This study proposes a patient-specific approach based on generative adversarial networks. In the presented training pipeline, the user trains a patient-specific segmentation network with extremely limited data which is supplemented with artificial samples generated by generative adversarial models. This approach is demonstrated in endoscopic video data captured during fetoscopic laser coagulation, a procedure used for treating twin-to-twin transfusion syndrome by ablating the placental blood vessels. Compared to a standard deep learning segmentation approach, the pipeline was able to achieve an intersection over union score of 0.60 using only 20 annotated images compared to 100 images using a standard approach. Furthermore, training with 20 annotated images without the use of the pipeline achieves an intersection over union score of 0.30, which, therefore, corresponds to a 100% increase in performance when incorporating the pipeline. A pipeline using GANs was used to generate artificial data which supplements the real data, this allows patient-specific training of a segmentation network. We show that artificial images generated using GANs significantly improve performance in vessel segmentation and that training patient-specific models can be a viable solution to bring automated vessel segmentation to the clinic.
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Placenta , Humanos , Embarazo , Placenta/irrigación sanguínea , Placenta/diagnóstico por imagen , Femenino , Aprendizaje Profundo , Procesamiento de Imagen Asistido por Computador/métodos , Transfusión Feto-Fetal/cirugía , Transfusión Feto-Fetal/diagnóstico por imagen , Aprendizaje Automático , Procedimientos Quirúrgicos Robotizados/métodos , Redes Neurales de la ComputaciónRESUMEN
Studying human skin biology can aid in comprehending the pathophysiology of skin diseases and developing novel cell-based therapies, including tissue engineering approaches. This chapter provides a comprehensive guide of methods to determine human skin samples from the perspective of their cellular compositions. We describe as useful technique the histological analysis of tissue sections. We further illustrate the biological characterization of isolated and cultured basal and suprabasal interfollicular keratinocytes by cell sorting, cytospin immunostaining, colony forming efficiency, and long-term dermo-epidermal organotypic cultures.
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Separación Celular , Células Epidérmicas , Queratinocitos , Células Madre , Humanos , Queratinocitos/citología , Queratinocitos/metabolismo , Separación Celular/métodos , Células Madre/citología , Células Madre/metabolismo , Células Epidérmicas/citología , Células Epidérmicas/metabolismo , Técnicas de Cultivo de Célula/métodos , Células Cultivadas , Piel/citología , Epidermis/metabolismo , Ingeniería de Tejidos/métodos , Diferenciación CelularRESUMEN
INTRODUCTION: Reduced middle cerebral artery resistance indices (MCA-RI) in fetuses with spina bifida (fSB) are commonly observed. Compression of neuronal pathways in the brainstem due to hindbrain herniation (HH) and disturbed cerebrospinal fluid circulation likely cause an imbalance of the autonomic nervous system. This may increase systemic vasoconstriction and compensatory increase cerebral vasodilation (like brain sparing). The aim of this study was to systematically analyze all fetal MCA-RI before and after fSB repair and to compare their correlation with the presence and postsurgical resolution of HH. METHODS: 173 patients were included. Standardized ultrasound examinations including MCA and umbilical artery (UA) Doppler as well as assessment of HH presence and regression were performed. Fetuses with MCA-RI <5th percentile (P) before fetal surgery were compared to the group with normal MCA-RI and correlated to the presence of HH before and its regression after fSB repair. RESULTS: 30% (49/161) fetuses showed RI's <5th P before fSB repair. All fetuses had normal UA-RI. 99.4% of fetuses (160/161) showed normal of MCA-RI before delivery. Normalization occurred within a mean of 1.3 ± 1.2 weeks. HH regression was observed in 97% in the group with normal MCA-RI and in 96% in the group with MCA-RI <5th P before surgery (p = 0.59). Time lapse to HH regression after fSB repair was 1.8 ± 1.7 and 1.9 ± 1.6 weeks, respectively. CONCLUSION: In fetuses with MCA-RIs <5 P before fSB repair, a parallel timely course of MCA-RI normalization and HH regression was noted. To suggest common pathogenic factor(s), more studies are needed. However, normalization of the fetal cerebral circulation could be a further benefit of fSB repair.
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INTRODUCTION: Studies have shown a high prevalence of sleep-disordered breathing (SDB) in children with spina bifida. International standards for regular testing for SDB in this population are lacking. While there are studies investigating the prevalence of SDB in children with spina bifida, there are close to no studies in neonates. AIM AND OBJECTIVE: To evaluate if routine respiratory polygraphy (RPG) testing is indicated for neonates with spina bifida and if yes, with what therapeutic consequence. METHODS: We conducted a retrospective cohort study of all neonates with spina bifida at the University (Children's) Hospital Zurich after fetal spina bifida repair born between 2017 and 2022, who had undergone at least 1 RPG evaluation during hospitalization on the neonatal ward. RPG were evaluated by a blinded group of experienced pediatric pulmonologists. Based on the neonatal RPG results and pediatric pulmonologist's recommendation for caffeine therapy the spina bifida cohort was divided into two groups. Neonatal baseline RPG and follow-up RPG at the age of the 3 months were evaluated. RESULTS: 48 neonates with RPG were included. Compared to the standard values in healthy neonates, the RPG results of this spina bifida cohort showed findings of SDB with central apnea and hypopnea. 22 (45.8%) neonatal RPG evaluations detected central SDB, prompting caffeine therapy. Follow-up RPG conducted after 3 months showed significant improvement of SDB with (almost) no need for continuation of caffeine. CONCLUSION: We recommend the implementation of routine RPG testing in neonates with spina bifida to detect SDB and facilitate early targeted treatment.
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Prenatal surgery for the treatment of spina bifida (myelomeningocele, MMC) significantly enhances the neurological prognosis of the patient. To ensure better protection of the spinal cord by large defects, the application of skin grafts produced with cells gained from the amniotic fluid is presently studied. In order to determine the most appropriate cells for this purpose, we tried to shed light on the extremely complex amniotic fluid cellular composition in healthy and MMC pregnancies. We exploited the potential of micro-Raman spectroscopy to analyse and characterize human amniotic fluid cells in total and putative (cKit/CD117-positive) stem cells of fetuses with MMC in comparison with amniotic fluid cells from healthy individuals, human fetal dermal fibroblasts and adult adipose derived stem cells. We found that (i) the differences between healthy and MMC amniocytes can be attributed to specific spectral regions involving collagen, lipids, sugars, tryptophan, aspartate, glutamate, and carotenoids, (ii) MMC amniotic fluid contains two particular cell populations which are absent or reduced in normal pregnancies, (iii) the cKit-negative healthy amniocyte subpopulation shares molecular features with human fetal fibroblasts. On the one hand we demonstrate a different amniotic fluid cellular composition in healthy and MMC pregnancies, on the other our work confirms micro-Raman spectroscopy to be a valuable tool for discriminating cell populations in unknown mixtures of cells.
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Líquido Amniótico , Feto , Meningomielocele , Espectrometría Raman , Humanos , Espectrometría Raman/métodos , Líquido Amniótico/citología , Líquido Amniótico/metabolismo , Meningomielocele/metabolismo , Meningomielocele/patología , Femenino , Embarazo , Feto/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patología , Células Cultivadas , AdultoRESUMEN
INTRODUCTION: In fetal surgery, successful pain management is crucial for postoperative mobilization, prophylaxis of contractions, and fast recovery. This study analyzed patient's pain experience after open fetal spina bifida (fSB) repair in comparison to pain scores after the subsequent Caesarean section (C-section). MATERIALS AND METHODS: Data were collected with a questionnaire given to 91 women, who had fSB repair and then C-section at our center between 2019 and 2022. It comprised 12 questions covering different aspects of pain experience and satisfaction with pain therapy and was answered by 67 women after fSB repair and 53 after C-section. Postoperative pain was rated on a Likert scale from 0 (slight/rarely) to 100 (strongest/always). Outcomes after fSB repair were compared to those after C-section. Additionally, subgroup analysis compared outcomes of women with different pain levels (group 1-5) after fSB repair. RESULTS: Compared to women after C-section women after fSB repair reported significantly higher maximum pain scores (MPS) (p = 0.03), higher sleep disturbance due to pain (p = 0.03), and sedation rates (p = 0.001) as side effect from pain therapy. No differences were found regarding feelings of insecurity (p = 0.20) or helplessness (p = 0.40), as well as involvement in (p = 0.3) and satisfaction with pain therapy (p = 0.5). Subgroup analysis revealed that women with higher MPS after fSB repair were significantly more often non-Caucasians (p = 0.003) and more often affected by pain while lying in bed (p = 0.007) and during mobilization (p = 0.005). Additionally, they reported higher rates of dizziness (p = 0.02) and lower satisfaction rates with pain therapy (p = 0.03). Postoperative complication rate did not differ among groups. CONCLUSION: Although women after fSB repair reported higher MPS compared to after C-section, the current pain management was generally perceived as satisfactory.
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Cesárea , Dimensión del Dolor , Dolor Postoperatorio , Humanos , Femenino , Cesárea/efectos adversos , Adulto , Embarazo , Dolor Postoperatorio/etiología , Dolor Postoperatorio/psicología , Estudios Longitudinales , Disrafia Espinal/cirugía , Disrafia Espinal/complicaciones , Disrafia Espinal/psicología , Encuestas y Cuestionarios , Satisfacción del Paciente , Manejo del Dolor/métodos , Estudios de CohortesRESUMEN
Endoscopes navigate within the human body to observe anatomical structures with minimal invasiveness. A major shortcoming of their use is their narrow field-of-view during navigation in large, hollow anatomical regions. Mosaics of endoscopic images can provide surgeons with a map of the tool's environment. This would facilitate procedures, improve their efficiency, and potentially generate better patient outcomes. The emergence of magnetically steered endoscopes opens the way to safer procedures and creates an opportunity to provide robotic assistance both in the generation of the mosaic map and in navigation within this map. This paper proposes methods to autonomously navigate magnetic endoscopes to 1) generate endoscopic image mosaics and 2) use these mosaics as user interfaces to navigate throughout the explored area. These are the first strategies, which allow autonomous magnetic navigation in large, hollow organs during minimally invasive surgeries. The feasibility of these methods is demonstrated experimentally both in vitro and ex vivo in the context of the treatment of twin-to-twin transfusion syndrome. This minimally invasive procedure is performed in utero and necessitates coagulating shared vessels of twin fetuses on the placenta. A mosaic of the vasculature in combination with autonomous navigation has the potential to significantly facilitate this challenging surgery.
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Endoscopía , Humanos , Endoscopía/métodos , Femenino , Transfusión Feto-Fetal/cirugía , Magnetismo/métodos , Endoscopios , Embarazo , Procedimientos Quirúrgicos Robotizados/métodosRESUMEN
INTRODUCTION: For open fetal spina bifida (fSB) repair, a maternal laparotomy is required. Hence, enhanced maternal recovery after surgery (ERAS) is paramount. A revision of our ERAS protocol was made, including changes in operative techniques and postoperative pain management. This study investigates eventual benefits. METHODS: Our study included 111 women with open fSB repair at our center. The old protocol group (group 1) either received a transverse incision of the fascia with transection of the rectus abdominis muscle (RAM) or a longitudinal incision of the fascia without RAM transection, depending on placental location. The new protocol required longitudinal incisions in all patients (group 2). Postoperative pain management was changed from tramadol to oxycodone/naloxone. Outcomes of the two different protocol groups were analyzed and compared regarding the primary endpoint, the length of hospital stay (LOS) after fetal surgery, as well as regarding the following secondary endpoints: postoperative pain scores, day of first mobilization, removal of urinary catheter, bowel movement, and the occurrence of maternal and fetal complications. RESULTS: Out of 111 women, 82 (73.9%) were in group 1 and 29 (26.1%) were in group 2. Women in group 2 showed a significantly shorter LOS (18 [14-23] days vs. 27 [18-39] days, p = 0.002), duration until mobilization (3 [2-3] days vs. 3 [3-4] days, p = 0.03), and removal of urinary catheter (day 3 [3-3] vs. day 4 [3-4], p = 0.004). Group 2 less often received morphine subcutaneously (0% vs. 35.4%, p < 0.001) or intravenously (0% vs. 17.1%, p = 0.02) but more often oxycodone (69.0% vs. 18.3%, p < 0.001). No significant differences were seen regarding pain scores, bowel movement, and maternal and/or fetal complications. CONCLUSION: The new ERAS protocol that combined changes in surgical technique and pain medication led to better outcomes while reducing LOS. Continuous revisions of current ERAS protocols are essential to improve patient care continuously.
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Recuperación Mejorada Después de la Cirugía , Dolor Postoperatorio , Disrafia Espinal , Humanos , Femenino , Disrafia Espinal/cirugía , Embarazo , Dolor Postoperatorio/etiología , Adulto , Tiempo de Internación , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
INTRODUCTION: The Management of Myelomeningocele Study (MOMS) eligibility criteria preclude in utero surgery for fetal spina bifida (fSB) when the maternal body mass index (BMI) is ≥35 kg/m2. Some centers still respect this criterion, while others, like ours, do not. This study aimed to assess whether maternal and fetal safety is compromised with higher maternal BMIs. METHODS: Data of 192 patients with open fSB repair at our center were retrospectively analyzed. According to their BMI, patients were divided into three groups: group 1 (BMI <30 kg/m2), group 2 (BMI 30-35 kg/m2), and group 3 (BMI >35 kg/m2). Subgroup analysis was performed to assess differences in maternal and fetal outcomes. Additionally, complications were divided into grades 1 to 5 according to their severity and outcome consequences and compared among groups. RESULTS: Out of 192 patients, 146 (76.0%) had a BMI <30 kg/m2, 28 (14.6%) had a BMI 30-35 kg/m2, and 18 (9.4%) had a BMI >35 kg/m2. Significant differences occurring more often in either group 2 or 3 compared to group 1 were maternal wound seroma (50% or 56% vs. 32%, p = 0.04), amniotic fluid leakage (14% or 6% vs. 2%, p = 0.01) as well as vaginal bleeding (11% or 35% vs. 9%, p = 0.01). On the contrary, duration of tocolysis with atosiban was shorter in patients with BMI >30 kg/m2 (4 or 5 vs. 6 days, p = 0.01). When comparing severity of maternal or fetal complications, grade 1 intervention-related complications occurred significantly more often in group 3 compared to group 1 or 2 (78% vs. 45% or 57%, p = 0.02). Gestational age at delivery was around 36 weeks in all groups without significant differences. CONCLUSION: This investigation did not identify clinically relevant maternal and/or fetal outcome problems related to BMIs >35 kg/m2. Additional studies are however needed to confirm our results.
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Meningomielocele , Espina Bífida Quística , Disrafia Espinal , Embarazo , Femenino , Humanos , Lactante , Estudios Retrospectivos , Feto/cirugía , Meningomielocele/cirugía , Meningomielocele/complicaciones , Obesidad/complicaciones , Disrafia Espinal/complicaciones , Disrafia Espinal/cirugía , Espina Bífida Quística/cirugíaRESUMEN
PURPOSE: This study aimed to describe outcomes of motor function with a special focus on ambulation ability at 36 months among children with open prenatal repair of spina bifida aperta (SB). METHODS: A prospective cohort study was conducted including 87 patients with open prenatal repair of SB at the investigating center born between 2010 and 2018. Anatomic lesion level and motor function level in the neonatal period, as well as motor function level, ambulation status, and use of orthotics and assistive devices at 36 months were assessed. RESULTS: At 36 months, ambulation was assessed in 86 children; of those, 86% (nâ=â74) were ambulating. Independent of ambulation, orthotics were worn in 81.6% (71/87) and assistive devices in 47.1% (41/87). Children with a lower lumbar or sacral motor function level were the first to reach independent ambulation and were more likely to ambulate at 36 months than children with higher motor function levels (pâ=â<â.001). The anatomic lesion level determined on the neonatal MRI correlated with ambulation status at 36 months (pâ=â<â0.001). CONCLUSION: At 36 months, most children with open prenatal repair for SB showed favourable ambulation status. However, most still used assistive devices or orthotics. Anatomic lesion level on neonatal MRI, motor function level during the neonatal period, and motor function level at 36 months were associated with ambulation status at 36 months.