Regional anesthesia and analgesia in patients with spastic cerebral palsy undergoing orthopedic surgery: a historical cohort study.

PURPOSE: We sought to examine the incidence of severe postoperative pain in patients with cerebral palsy (CP) in the first 48 hr after surgery performed under combined regional and general anesthesia and its association with patient and surgical factors. METHODS: In a historical cohort study, we reviewed the electronic records of 452 patients with spastic CP who underwent orthopedic surgeries of the upper and lower extremities from April 2016 to February 2020. Collected data included patient characteristics, American Society of Anesthesiologists Physical Status, details of anesthesia and surgery, types of regional anesthesia applied, success rate of anesthesia, incidence of severe pain, and adverse events. RESULTS: We analyzed data from 440 patients; 404 patients underwent lower extremity surgery, 20 upper extremity surgery, and 15 both, and one patient required stem cell injection. All patients received general anesthesia before block performance. Single-injection neuraxial anesthesia was performed in 241 (54.8%) patients, brachial plexus block in 27 (6.1%) patients, and femoral/sciatic nerve blocks in 17 (3.9%) patients. Continuous neuraxial, brachial plexus, and femoral/sciatic nerve blocks were performed in 149 (33.9%), four (0.9%), and seven (1.6%) of the patients, respectively. Major and complex major surgeries were performed in 161 (36.6%) and 72 (16.4%) patients, respectively and continuous catheters were inserted in 50.3% of patients undergoing major surgery and in 91.7% of patients undergoing complex major surgery. Severe pain was reported by the caregivers of 68 (15.5%) patients who received nonopioid analgesic interventions. CONCLUSION: Despite the use of regional anesthesia, approximately 15% of patients with spastic CP undergoing orthopedic surgery for spastic cerebral palsy experienced severe pain that responded to treatment adjustments. STUDY REGISTRATION: CTRI.nic.in (027002); registered 5 August 2020.

RéSUMé: OBJECTIF: Nous avons cherché à examiner l'incidence de la douleur postopératoire sévère chez les personnes atteintes de paralysie cérébrale (PC) au cours des 48 premières heures suivant une chirurgie réalisée sous anesthésie régionale et générale combinée et son association avec les facteurs liés aux patient·es et les facteurs chirurgicaux. MéTHODE: Dans une étude de cohorte historique, nous avons examiné les dossiers électroniques de 452 personnes atteintes de PC spastique ayant bénéficié de chirurgies orthopédiques des membres supérieurs et inférieurs d'avril 2016 à février 2020. Les données recueillies comprenaient les caractéristiques des patient·es, le statut physique selon l'American Society of Anesthesiologists, les détails de l'anesthésie et de la chirurgie, les types d'anesthésie régionale appliqués, le taux de réussite de l'anesthésie, l'incidence de la douleur intense et les événements indésirables. RéSULTATS: Nous avons analysé les données de 440 patient·es; 404 ont bénéficié d'une chirurgie des membres inférieurs, 20 d'une chirurgie des membres supérieurs et 15 des deux, et une personne a nécessité une injection de cellules souches. Tou·tes les patient·es ont reçu une anesthésie générale avant la réalisation du bloc. Une anesthésie neuraxiale à injection unique a été réalisée chez 241 patient·es (54,8 %), un bloc du plexus brachial chez 27 patient·es (6,1 %) et des blocs du nerf fémoral/sciatique chez 17 (3,9 %) patient·es. Des blocs nerveux neuraxiaux, du plexus brachial et fémoraux/sciatiques continus ont été réalisés chez 149 (33,9 %), quatre (0,9 %) et sept (1,6 %) personnes, respectivement. Des chirurgies majeures et complexes ont été réalisées chez 161 (36,6 %) et 72 (16,4 %) patient·es, respectivement, et des cathéters continus ont été insérés chez 50,3 % des personnes bénéficiant d'une intervention chirurgicale majeure et chez 91,7 % des personnes bénéficiant d'une chirurgie majeure complexe. Une douleur intense a été signalée par le personnel soignant chez 68 patient·es (15,5 %) ayant reçu des interventions analgésiques non opioïdes. CONCLUSION: Malgré l'utilisation de l'anesthésie régionale, environ 15 % des patient·es atteint·es de PC spastique bénéficiant d'une chirurgie orthopédique pour leur paralysie cérébrale spastique ont ressenti une douleur intense qui a répondu aux ajustements du traitement. ENREGISTREMENT DE L'éTUDE: CTRI.nic.in (027002); enregistrée le 5 août 2020.

Aggregation-induced emission (AIE) nanoparticles labeled human embryonic stem cells (hESCs)-derived neurons for transplantation.

Transplantation of differentiated neurons derived from either human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs) is an emerging therapeutic strategy for various neurodegenerative diseases. One important aspect of transplantation is the accessibility to track and control the activity of the stem cells-derived neurons post-transplantation. Recently, the characteristics of organic nanoparticles (NPs) with aggregation-induced emission (AIE) have emerged as efficient cell labeling reagents, where positive outcomes were observed in long-term cancer cell tracing in vivo. In the current study, we designed, synthesized, and analyzed the biocompatibility of AIE-NPs in cultured neurons such as in mouse neuronal progenitor cells (NPCs) and hESC-derived neurons. Our data demonstrated that AIE-NPs show high degree of penetration into cells and presented intracellular long-term retention in vitro without altering the neuronal proliferation, differentiation, and viability. Furthermore, we have tracked AIE-NPs labeled neuronal grafts in mouse brain striatum in various time points post-transplantation. We demonstrated prolonged cellular retention of AIE-NPs labeled neuronal grafts 1 month post-transplantation in mouse brain striatum. Lastly, we have shown activation of brain microglia in response to AIE-NPs labeled grafts. Together, these findings highlight the potential application of AIE-NPs in neuronal transplantation.

A microfiber scaffold-based 3D in vitro human neuronal culture model of Alzheimer's disease.

Increasing evidence indicates superiority of three-dimensional (3D) in vitro cell culture systems over conventional two-dimensional (2D) monolayer cultures in mimicking native in vivo microenvironments. Tissue-engineered 3D culture models combined with stem cell technologies have advanced Alzheimer's disease (AD) pathogenesis studies. However, existing 3D neuronal models of AD overexpress mutant genes or have heterogeneities in composition, biological properties and cell differentiation stages. Here, we encapsulate patient induced pluripotent stem cell (iPSC) derived neural progenitor cells (NPC) in poly(lactic-co-glycolic acid) (PLGA) microtopographic scaffolds fabricated via wet electrospinning to develop a novel 3D culture model of AD. First, we enhanced cellular infiltration and distribution inside the scaffold by optimizing various process parameters such as fiber diameter, pore size, porosity and hydrophilicity. Next, we compared key neural stem cell features including viability, proliferation and differentiation in 3D culture with 2D monolayer controls. The 3D microfibrous substrate reduces cell proliferation and significantly accelerates neuronal differentiation within seven days of culture. Furthermore, 3D culture spontaneously enhanced pathogenic amyloid-beta 42 (Aß42) and phospho-tau levels in differentiated neurons carrying familial AD (FAD) mutations, compared with age-matched healthy controls. Overall, our tunable scaffold-based 3D neuronal culture platform serves as a suitable in vitro model that robustly recapitulates and accelerates the pathogenic characteristics of FAD-iPSC derived neurons.

Dopamine transporter neuroimaging accurately assesses the maturation of dopamine neurons in a preclinical model of Parkinson's disease.

BACKGROUND: Significant developments in stem cell therapy for Parkinson's disease (PD) have already been achieved; however, methods for reliable assessment of dopamine neuron maturation in vivo are lacking. Establishing the efficacy of new cellular therapies using non-invasive methodologies will be critical for future regulatory approval and application. The current study examines the utility of neuroimaging to characterise the in vivo maturation, innervation and functional dopamine release of transplanted human embryonic stem cell-derived midbrain dopaminergic neurons (hESC-mDAs) in a preclinical model of PD. METHODS: Female NIH RNu rats received a unilateral stereotaxic injection of 6-OHDA into the left medial forebrain bundle to create the PD lesion. hESC-mDA cell and sham transplantations were carried out 1 month post-lesion, with treated animals receiving approximately 4 × 105 cells per transplantation. Behavioural analysis, [18F]FBCTT and [18F]fallypride microPET/CT, was conducted at 1, 3 and 6 months post-transplantation and compared with histological characterisation at 6 months. RESULTS: PET imaging revealed transplant survival and maturation into functional dopaminergic neurons. [18F]FBCTT-PET/CT dopamine transporter (DAT) imaging demonstrated pre-synaptic restoration and [18F]fallypride-PET/CT indicated functional dopamine release, whilst amphetamine-induced rotation showed significant behavioural recovery. Moreover, histology revealed that the grafted cells matured differently in vivo producing high- and low-tyrosine hydroxylase (TH) expressing cohorts, and only [18F]FBCTT uptake was well correlated with differentiation. CONCLUSIONS: This study provides further evidence for the value of in vivo functional imaging for the assessment of cell therapies and highlights the utility of DAT imaging for the determination of early post-transplant cell maturation and differentiation of hESC-mDAs.