A Novel Minimally Invasive Surgically Induced Skeletal Muscle Injury Model in Sheep.

Sports-related muscle injuries account for 10-55% of all injuries, which is a growing concern, especially given the aging world population. To evaluate the process of skeletal muscle injury and compare it with muscle lesions observed in humans, we developed a novel in vivo model in sheep. In this model, muscle injury was induced by an ultrasound-guided transverse biopsy at the myotendinous junction of the medial gastrocnemius muscle. Twelve male sheep were examined at 3, 7, 14, and 28 days post-injury. Histological, immunofluorescence, and MRI analyses indicate that our sheep model could resemble key human clinicopathological features. Statistically significant differences (p < 0.05) were observed in collagen I, dMHC, α-SMA, and CD68 immunohistochemical detection when comparing injured and healthy muscles. The injured gastrocnemius muscle exhibited elevated levels of type I collagen, infiltration of CD68(+) macrophages, angiogenesis, and the emergence of newly regenerated dMHC(+) myofibers, which persisted for up to 4 weeks post-injury. Similarly, the progression of muscle injury in the sheep model was assessed using advanced clinical 3 T MRI and compared with MRI scans from human patients. The data indicate that the sheep muscle injury model presents features similar to those observed in human skeletal muscle injuries. This makes it a valuable large animal model for studying muscle injuries and developing novel therapeutic strategies.

Maternal anaesthesia in open and fetoscopic surgery of foetal open spinal neural tube defects: A retrospective cohort study.

BACKGROUND: Prenatal myelomeningocele repair by open surgery can improve the neurological prognosis of children with this condition. A shift towards a fetoscopic approach seems to reduce maternal risks and improve obstetric outcomes. OBJECTIVE: The aim of this study was to report on the anaesthetic management of women undergoing prenatal open or fetoscopic surgery for neural tube defects. DESIGN: A retrospective cohort study. SETTING: Prenatal myelomeningocele repair research group, Vall d'Hebron University Hospital, Spain. INTERVENTION: Intra-uterine foetal repairs of spina bifida between 2011 and 2016 were reviewed. Anaesthetic and vasoconstrictor drugs, fluid therapy, maternal haemodynamic changes during surgery, blood gas changes during CO2 insufflation for fetoscopic surgery, and maternal and foetal complications were noted. RESULTS: Twenty-nine foetuses with a neural tube defect underwent surgery, seven (24.1%) with open and 22 (75.9%) with fetoscopic surgery. There were no significant differences in maternal doses of opioids or neuromuscular blocking agents. Open surgery was associated with higher dose of halogenated anaesthetic agents [maximum medium alveolar concentration (MAC) sevoflurane 1.90 vs. 1.50%, P = 0.01], higher need for intra-operative tocolytic drugs [five of seven (71.4%) and two of 22 (9.1%) required nitroglycerine, P = 0.001], higher volume of colloids (500 vs. 300 ml, P = 0.036) and more postoperative tocolytic drugs (three drugs in all seven cases (100%) of open and in one of 21 (4.76%) of fetoscopic surgery, P < 0.001). Median mean arterial pressure was lower in open than in fetoscopic surgery. SBP, DBP and mean blood pressure decreased during uterine exposure, and this descent was more acute in open surgery. Use of vasoconstrictor drugs was related to the time of uterine exposure, but not to surgical technique. Blood gas analysis was not affected by CO2 insufflation during fetoscopic surgery. CONCLUSION: Open surgery was associated with more maternal haemodynamic changes and higher doses of halogenated anaesthetic and tocolytics agents than fetoscopic surgery.

Isolation, characterization, and differentiation of multipotent neural progenitor cells from human cerebrospinal fluid in fetal cystic myelomeningocele.

Despite benefits of prenatal in utero repair of myelomeningocele, a severe type of spina bifida aperta, many of these patients will still suffer mild to severe impairment. One potential source of stem cells for new regenerative medicine-based therapeutic approaches for spinal cord injury repair is neural progenitor cells (NPCs) in cerebrospinal fluid (CSF). To this aim, we extracted CSF from the cyst surrounding the exposed neural placode during the surgical repair of myelomeningocele in 6 fetuses (20 to 26weeks of gestation). In primary cultured CSF-derived cells, neurogenic properties were confirmed by in vitro differentiation into various neural lineage cell types, and NPC markers expression (TBR2, CD15, SOX2) were detected by immunofluorescence and RT-PCR analysis. Differentiation into three neural lineages was corroborated by arbitrary differentiation (depletion of growths factors) or explicit differentiation as neuronal, astrocyte, or oligodendrocyte cell types using specific induction mediums. Differentiated cells showed the specific expression of neural differentiation markers (ßIII-tubulin, GFAP, CNPase, oligo-O1). In myelomeningocele patients, CSF-derived cells could become a potential source of NPCs with neurogenic capacity. Our findings support the development of innovative stem-cell-based therapeutics by autologous transplantation of CSF-derived NPCs in damaged spinal cords, such as myelomeningocele, thus promoting neural tissue regeneration in fetuses.

The quantitative lung index and the prediction of survival in fetuses with congenital diaphragmatic hernia.

INTRODUCTION: The lung-to-head ratio (LHR) is routinely used to select the best candidates for prenatal surgery and to follow-up the fetuses with congenital diaphragmatic hernia (CDH). Since this index is gestation-dependent, the quantitative lung index (QLI) was proposed as an alternative parameter that stays constant throughout pregnancy. Our objective was to study the performance of QLI to predict survival in fetuses with CDH. MATERIALS AND METHODS: Observational retrospective study of fetuses with isolated CDH, referred to our center. LHR was originally used for the prenatal surgery evaluation. We calculated the QLI and compared the performance of both indexes (QLI and LHR) to predict survival. RESULTS: From January-2009 to February-2015 we followed 31 fetuses with isolated CDH. The mean QLI was 0.66 (95% CI: 0.57-0.75) for survivors and 0.41 (95% CI: 0.25-0.58) for non-survivors (p<0.01) and the mean LHR was 1.38 (95% CI: 1.17-1.60) for survivors and 0.91 (95% CI: 0.57-1.25) for non-survivors (p<0.02). All operated fetuses (n=12) had a LHR <1 and a QLI <0.5 and none of them survived when the QLI was <0.32. When separately considering the prenatal surgery status, the mean values of the QLI (but not those of the LHR) were still significantly different between survivors and non-survivors. The comparative ROC curves showed a better performance of the QLI with respect to the LHR for the prediction of survival, especially in the group of operated fetuses, although differences were not statistically significant. COMMENT: The QLI seems to be a better predictor for survival than the LHR, especially for the group of fetuses undergoing prenatal surgery.