High-Fidelity Low-Cost Synthetic Training Model for Fetoscopic Spina Bifida Repair

BACKGROUND: Fetoscopic Spina Bifida repair (fSB-repair) is increasingly being practiced, but limited skill acquisition poses a barrier to widespread adoption. Extensive training in relevant models, including both ex- and in-vivo models may help. To address this, a synthetic training model that is affordable, realistic and allows skill analysis would be useful.OBJECTIVE: To create a high-fidelity model for training the essential neurosurgical steps of fetoscopic spina bifida repair using synthetic materials. Additionally, we aimed to obtain a cheap and easily reproducible model.STUDY DESIGN: We developed a three-layered silicon-based model resembling the anatomical layers of a typical myelomeningocele lesion. It allows for filling the cyst with fluid and conducting a water tightness test post-repair. A compliant silicon ball mimics the uterine cavity, and is fixed to a solid 3D printed base. The fetal back with the lesion (single-use) is placed inside the uterine ball, which is reusable and repairable to allow practicing port insertion and fixation multiple times. Following cannula insertion, the uterus is insufflated, and clinical fetoscopic, robotic or prototype instruments can be used. Three skilled endoscopic surgeons each did six simulated fetoscopic repairs following the surgical steps of an open repair. The primary outcome was surgical success, based on water tightness of the repair, operation time &lt;180 minutes and an Objective-Structured-Assessment-of-Technical-Skills (OSATS)-score of ≥ 18/25. Skill retention was measured using a competence commulative sum (C-CUSUM) analysis on composite binary outcome for surgical success. Secondary outcomes were cost and fabrication time of the model.RESULTS: We made a model for simulating spina bifida repair neurosurgical steps with anatomical details, port insertion, placode release and descent, undermining of skin and muscular layer, and endoscopic suturing. The model is made with reusable 3D-printed molds with easily accessible materials. The one-time startup cost was 211€, and each single-use simulated MMC-lesion costs 9.5€ in materials and 50 min working hours. Two skilled endoscopic surgeons performed six simulated three-port fetoscopic repairs, while a third used a Da-Vinci surgical robot. Operation times decreased over 30% from the first to last trial. Six experiments per surgeon did not show an obvious OSATS-score improvement. C-CUSUM analysis confirmed competency for each surgeon.CONCLUSION: This high-fidelity low-cost spina bifida model allows simulated dissection and closure of a myelomeningocele lesion.</p

Prenatal treprostinil improves pulmonary arteriolar hypermuscularization in the rabbit model of congenital diaphragmatic hernia

Congenital diaphragmatic hernia (CDH) is a congenital malformation characterized by pulmonary hypoplasia, pulmonary hypertension, and cardiac dysfunction. Pulmonary hypertension represents the major cause of neonatal mortality and morbidity. Prenatal diagnosis allows assessment of severity and selection of foetal surgery candidates. We have shown that treprostinil, a prostacyclin analogue with an anti-remodelling effect, attenuates the relative hypermuscularization of the pulmonary vasculature in rats with nitrofen-induced CDH. Here we confirm these observations in a large animal model of surgically-created CDH. In the rabbit model, subcutaneous maternal administration of treprostinil at 150 ng/kg/min consistently reached target foetal concentrations without demonstrable detrimental foetal or maternal adverse effects. In pups with CDH, prenatal treprostinil reduced pulmonary arteriolar proportional medial wall thickness and downregulated inflammation and myogenesis pathways. No effect on alveolar morphometry or lung mechanics was observed. These findings provide further support towards clinical translation of prenatal treprostinil for CDH.</p

Historical extension of operational NDVI products for livestock insurance in Kenya

Droughts induce livestock losses that severely affect Kenyan pastoralists. Recent index insurance schemes have the potential of being a viable tool for insuring pastoralists against drought-related risk. Such schemes require as input a forage scarcity (or drought) index that can be reliably updated in near real-time, and that strongly relates to livestock mortality. Generally, a long record (>25 years) of the index is needed to correctly estimate mortality risk and calculate the related insurance premium. Data from current operational satellites used for large-scale vegetation monitoring span over a maximum of 15 years, a time period that is considered insufficient for accurate premium computation. This study examines how operational NDVI datasets compare to, and could be combined with the non-operational recently constructed 30-year GIMMS AVHRR record (1981–2011) to provide a near-real time drought index with a long term archive for the arid lands of Kenya. We compared six freely available, near-real time NDVI products: five from MODIS and one from SPOT-VEGETATION. Prior to comparison, all datasets were averaged in time for the two vegetative seasons in Kenya, and aggregated spatially at the administrative division level at which the insurance is offered. The feasibility of extending the resulting aggregated drought indices back in time was assessed using jackknifed R2 statistics (leave-one-year-out) for the overlapping period 2002–2011. We found that division-specific models were more effective than a global model for linking the division-level temporal variability of the index between NDVI products. Based on our results, good scope exists for historically extending the aggregated drought index, thus providing a longer operational record for insurance purposes. We showed that this extension may have large effects on the calculated insurance premium. Finally, we discuss several possible improvements to the drought index

Differences in pain, function and coping in Multidimensional Pain Inventory subgroups of chronic back pain: a one-group pretest-posttest study

Contains fulltext : 97819.pdf (publisher's version ) (Open Access)BACKGROUND: Patients with non-specific back pain are not a homogeneous group but heterogeneous with regard to their bio-psycho-social impairments. This study examined a sample of 173 highly disabled patients with chronic back pain to find out how the three subgroups based on the Multidimensional Pain Inventory (MPI) differed in their response to an inpatient pain management program. METHODS: Subgroup classification was conducted by cluster analysis using MPI subscale scores at entry into the program. At program entry and at discharge after four weeks, participants completed the MPI, the MOS Short Form-36 (SF-36), the Hospital Anxiety and Depression Scale (HADS), and the Coping Strategies Questionnaire (CSQ). Pairwise analyses of the score changes of the mentioned outcomes of the three MPI subgroups were performed using the Mann-Whitney-U-test for significance. RESULTS: Cluster analysis identified three MPI subgroups in this highly disabled sample: a dysfunctional, interpersonally distressed and an adaptive copers subgroup. The dysfunctional subgroup (29% of the sample) showed the highest level of depression in SF-36 mental health (33.4 +/- 13.9), the interpersonally distressed subgroup (35% of the sample) a modest level of depression (46.8 +/- 20.4), and the adaptive copers subgroup (32% of the sample) the lowest level of depression (57.8 +/- 19.1). Significant differences in pain reduction and improvement of mental health and coping were observed across the three MPI subgroups, i.e. the effect sizes for MPI pain reduction were: 0.84 (0.44-1.24) for the dysfunctional subgroup, 1.22 (0.86-1.58) for the adaptive copers subgroup, and 0.53 (0.24-0.81) for the interpersonally distressed subgroup (p = 0.006 for pairwise comparison). Significant score changes between subgroups concerning activities and physical functioning could not be identified. CONCLUSIONS: MPI subgroup classification showed significant differences in score changes for pain, mental health and coping. These findings underscore the importance of assessing individual differences to understand how patients adjust to chronic back pain

Examination of Late Palaeolithic archaeological sites in northern Europe for the preservation of cryptotephra layers

We report the first major study of cryptotephra (non-visible volcanic ash layers) on Late Palaeolithic archaeological sites in northern Europe. Examination of 34 sites dating from the Last Termination reveals seven with identifiable cryptotephra layers. Preservation is observed in minerogenic and organic deposits, although tephra is more common in organic sediments. Cryptotephra layers normally occur stratigraphically above or below the archaeology. Nearby off-site palaeoclimate archives (peat bogs and lakes &lt;0.3 km distant) were better locations for detecting tephra. However in most cases the archaeology can only be correlated indirectly with such cryptotephras. Patterns affecting the presence/absence of cryptotephra include geographic position of sites relative to the emitting volcanic centre; the influence of past atmospherics on the quantity, direction and patterns of cryptotephra transport; the nature and timing of local site sedimentation; sampling considerations and subsequent taphonomic processes. Overall, while tephrostratigraphy has the potential to improve significantly the chronology of such sites many limiting factors currently impacts the successful application

Safety and efficacy of fetal surgery techniques to close a spina bifida defect in the fetal lamb model: a systematic review

To determine the safety and efficacy of different neurosurgical techniques for closure of spina bifida (SB) in the fetal lamb model.status: publishe

Artificial placenta and womb technology: past, current and future challenges towards clinical translation.

Extreme prematurity remains a major cause of neonatal mortality and severe long-term morbidity. Current neonatal care is associated with significant morbidity due to iatrogenic injury and developmental immaturity of extreme premature infants. A more physiologic approach, replacing placental function and providing a womb-like environment, is the foundational principle of artificial placenta (AP) and womb (AW) technology. The concept has been studied during the past 60 years with limited success. However, recent technological advancements and a greater emphasis on mimicking utero-placental physiology have improved the success of experimental models, bringing the technology closer to clinical translation. Here, we review the rationale for and history of AP and AW technology, discuss the challenges that needed to be overcome, and compare recent successful models. We conclude by outlining some remaining challenges to be addressed on the path towards clinical translation and opportunities for future research.status: accepte

Sildenafil for Antenatal Treatment of Congenital Diaphragmatic Hernia: From Bench to Bedside

BACKGROUND: Persistent pulmonary hypertension (PPH) is one of the main causes of mortality and morbidity in infants affected by congenital diaphragmatic hernia (CDH). Since the structural changes that lead to PPH take place already in utero, a treatment starting in the prenatal phase may prevent the occurrence of this complication. OBJECTIVE: To summarize the development process of antenatal sildenafil for CDH. METHODS: The pharmacokinetics and efficacy of sildenafil have been assessed in the rat and the rabbit model. The transfer of the drug through the human placenta has been measured with the ex-vivo placenta perfusion model. Results from this experiment are being incorporated in a pregnancy-physiologically based pharmacokinetic (p- PBPK) model. A phase I-IIb placental transfer and safety study is ongoing. RESULTS: Sildenafil administration to pregnant rats and rabbits led to therapeutic foetal drug levels without maternal and foetal toxicity, although it was associated with impaired vascular development in foetuses with nonhypoplastic lungs. Peak concentrations and 24-hour exposure were higher in pregnant rabbits compared to nonpregnant ones. In rat and rabbit foetuses with CDH, sildenafil rescued the lung vascular anomalies and partially improved parenchymal development. Sildenafil crossed the human placenta at a high rate ex-vivo, independently from the initial maternal concentration. CONCLUSION: There is preclinical evidence that maternally administered sildenafil prevents the vascular changes that lead to PPH in CDH newborns. The phase I/IIb clinical study together with the p-PBPK model will define the maternal dose needed for a therapeutic effect in the foetus. Foetal safety will be investigated both in the clinical study and in the sheep. The final step will be a multicentre, randomized, placebo-controlled trial.status: publishe

Sildenafil during the 2nd and 3rd Trimester of Pregnancy: Trials and Tribulations

Sildenafil, a phosphodiesterase 5 inhibitor with a vasodilatory and anti-remodeling effect, has been investigated concerning various conditions during pregnancy. Per indication, we herein review the rationale and the most relevant experimental and clinical studies, including systematic reviews and meta-analyses, when available. Indications for using sildenafil during the second and third trimester of pregnancy include maternal pulmonary hypertension, preeclampsia, preterm labor, fetal growth restriction, oligohydramnios, fetal distress, and congenital diaphragmatic hernia. For most indications, the rationale for administering prenatal sildenafil is based on limited, equivocal data from in vitro studies and rodent disease models. Clinical studies report mild maternal side effects and suggest good fetal tolerance and safety depending on the underlying pathology