Seizures as presentation of shunt malfunction: tertiary paediatric neurosurgery experience.

AIM: Patients with a background of cerebrospinal fluid (CSF)-diverting shunts are frequently investigated for shunt malfunction when presenting with seizures. However, there is very limited evidence in the literature regarding the association of seizures and shunt malfunction. We sought to determine the incidence of shunt malfunction in our cohort of shunted paediatric patients presenting with seizures, and the utility of seizures as a marker of shunt malfunction. METHODS: We retrospectively identified all shunted patients presenting with seizures, as well as all patients undergoing shunt revision following a presentation with seizures from our hospital database over a 14-year period from 2009 to 2023. Data gathered included demographics, de novo seizures or change in pattern of seizures, the aetiology of hydrocephalus and the segment of shunt requiring revision. Exclusion criteria included infected cases requiring shunt externalisation. A literature review of all papers discussing seizures as a presentation of shunt malfunction was also carried out. RESULTS: Overall, over a 14-year period of study, 338 shunted patients presented with seizures and were referred as suspected shunt malfunction with 10 having confirmed shunt malfunction requiring revision (2.9%). This group represented 6.2% of 161 cases of shunt revision carried out during the 14-year period of study. Post-haemorrhagic hydrocephalus secondary to prematurity was the commonest aetiology of shunted hydrocephalus presenting with seizures. Out of 10 patients presenting with seizures with shunt malfunction, 4 presented with de novo seizures, while 6 presented with a change in seizure pattern or frequency in already known epileptic patients. Shunt revision surgeries included 5 distal catheter, 2 proximal catheter, 1 proximal catheter-valve, 1 valve only and 1 case of whole shunt change. CONCLUSION: Our data supports that seizures are rare manifestation of shunt malfunction and can present either de novo or with a change in seizure frequency in already-known epileptic patients.

Parental diagnosis of shunt malfunction in children.

IntroductionEvaluation of shunt for malfunction and blockage is a common neurosurgical clinical scenario in day-to-day paediatric neurosurgery practice. Parental concern for shunt malfunction is normally considered a reliable indication for undertaking further assessment of a child with a shunt. Accuracy of parental diagnosis of shunt malfunction likely is dependent on combination of parental knowledge and patient symptomatology and familiarity of symptoms in relation to previous shunt malfunction symptoms. There are currently no UK studies on accuracy of parental diagnosis of shunt malfunction. We undertook this study to investigate sensitivity and specificity of parental diagnosis in our tertiary paediatric neurosurgical unit to identify any factors that can be used for further education and raising awareness in parents with children with shunts.MethodsWe undertook a review of all referrals with suspected shunt malfunction to our tertiary paediatric neurosurgical unit over a period of 10 months. All referrals and presentations were evaluated for parental concern for likelihood of shunt malfunction and marked as yes or no. Further information gathered included demographics, age, sex, symptoms at presentation, previous history of shunt revision, cases of shunt malfunction and part of the shunt revised. Sensitivity, specificity, positive and negative predictive values and accuracy were then calculated and factors associated with positive diagnosis of shunt malfunction analysed.ResultsOverall, 100 referrals with suspected shunt malfunction were made over 10 months period. Mean age for children at the time of referral was 6.3 years with an M/F ratio of 42M:58F. Twenty-one shunt malfunction cases were identified leading to overall revision rate of 21%. Parental evaluation of shunt function had sensitivity of 90.4%, specificity of 10.1%, positive predictive value of 21.1% and negative predictive value of 80%. Drowsiness and higher number of symptoms at presentation were associated with true positive diagnosis of shunt malfunction. No link was identified with true diagnosis of shunt malfunction with other symptoms of shunt malfunction or previous history of shunt revision and age of the patient.ConclusionParental diagnosis of shunt malfunction has high sensitivity and negative predictive value and low specificity and positive predictive value. Increased number of symptoms as well as drowsiness were associated with correct parental diagnosis of shunt malfunction. Educational programs and parental training can be valuable in increasing awareness about shunt malfunction signs.

Chemically Triggered Changes in Mechanical Properties of Responsive Liquid Crystal Polymer Networks with Immobilized Urease.

Liquid crystal polymer networks (LCNs) are stimuli-responsive materials that can be programmed to realize spatial variation in mechanical response and undergo shape transformation. Herein, we report a process to introduce chemical specificity to the stimuli response of LCNs by integrating enzymes as molecular triggers. Specifically, the enzyme urease was immobilized in LCN films via acyl fluoride conjugation chemistry. Activity assays and confocal fluorescence imaging confirmed retention of urease activity after immobilization as well as widespread distribution of enzyme on the film. The addition of urea triggered a response in the LCN whereby newly generated ammonia reacted with free acyl fluorides to form benzamide moieties. These moieties were capable of dimerizing through the formation of supramolecular hydrogen bonds, which was reflected in a 4-fold increase in Young's modulus. Through dynamic mechanical analysis and calorimetry, we further confirmed that the degree of hydrogen bonding in the LCNs could be judiciously designed to fine-tune the mechanical properties and glass transition temperature. These findings demonstrate the untapped potential of biochemical mechanisms as molecular triggers in LCNs and open the door to the use of nucleophilic chemistries in modulating the mechanical properties of LCNs.

Chyloperitoneum following open myelomeningocele repair: dealing with an extremely rare finding.

PURPOSE: Chyloperitoneum is an extremely rare finding following myelomeningocele (MMC) repair in neonates. We aimed to describe the characteristics of such a case and explore its clinical significance. CASE REPORT: A male baby born at term with open MMC and hydrocephalus underwent MMC repair surgery with rotational flaps on the first postnatal day. The procedure was uneventful. Three days later, he underwent a right ventriculoperitoneal shunt (VPS) insertion. On opening the peritoneum, a remarkable amount of yellowish opaque fluid was observed. Chyloperitoneum was suspected, but the VPS procedure was completed as planned. Biochemical analysis was consistent with that of chyle. DISCUSSION: Neonatal chylous ascites is a rare condition; hence, available data on pathophysiology and therapy in the literature are scarce. It is postulated that the MMC repair in neonates causes abdominal tautness, which leads to rupture of small lymphatics and raised intraportal pressure. The combination of these two processes results in extravasation of chyle from the gastrointestinal tract. Presence of chyloperitoneum is not a contraindication for VPS insertion. CONCLUSION: Chyloperitoneum is an extremely rare sequela of MMC repair in neonates. Pediatric neurosurgeons should be aware of it, especially when a VPS procedure is to follow a repair, in order to know how to deal with it and avoid unnecessary abandonment of the shunt.

The 'transverse guard' wound dressing technique to reduce faecal contamination after spinal surgery in neonates and infants.

Wound care following lower spinal surgery in infants, especially open lumbosacral myelomeningocele (MMC) repair is challenging for a number of reasons: the babies' small size, uneven contour of the natal cleft, proximity of the wound to the perianal area, continuous soiling by loose/poorly-formed stool, and fragile skin. Faecal contamination of the wound can lead to infection, ascending meningitis and further morbidity. A single adhesive dressing does not reliably obliterate the space in the natal cleft and, therefore, does not prevent faecal material tracking rostrally underneath the dressing. This increases the risk of contamination and necessitates frequent wound dressing changes. The authors describe the use of the 'transverse guard', a simple technique routinely used in their unit that help overcome these problems. They also report on the wound infection rates of neonates undergoing open MMC repair who had the new dressings versus those who had conventional dressings.

Stiffness anisotropy coordinates supracellular contractility driving long-range myotube-ECM alignment.

The ability of cells to organize into tissues with proper structure and function requires the effective coordination of proliferation, migration, polarization, and differentiation across length scales. Skeletal muscle is innately anisotropic; however, few biomaterials can emulate mechanical anisotropy to determine its influence on tissue patterning without introducing confounding topography. Here, we demonstrate that substrate stiffness anisotropy coordinates contractility-driven collective cellular dynamics resulting in C2C12 myotube alignment over millimeter-scale distances. When cultured on mechanically anisotropic liquid crystalline polymer networks (LCNs) lacking topography, C2C12 myoblasts collectively polarize in the stiffest direction. Cellular coordination is amplified through reciprocal cell-ECM dynamics that emerge during fusion, driving global myotube-ECM ordering. Conversely, myotube alignment was restricted to small local domains with no directional preference on mechanically isotropic LCNs of the same chemical formulation. These findings provide valuable insights for designing biomaterials that mimic anisotropic microenvironments and underscore the importance of stiffness anisotropy in orchestrating tissue morphogenesis.

Circularity in polymers: addressing performance and sustainability challenges using dynamic covalent chemistries.

The circularity of current and future polymeric materials is a major focus of fundamental and applied research, as undesirable end-of-life outcomes and waste accumulation are global problems that impact our society. The recycling or repurposing of thermoplastics and thermosets is an attractive solution to these issues, yet both options are encumbered by poor property retention upon reuse, along with heterogeneities in common waste streams that limit property optimization. Dynamic covalent chemistry, when applied to polymeric materials, enables the targeted design of reversible bonds that can be tailored to specific reprocessing conditions to help address conventional recycling challenges. In this review, we highlight the key features of several dynamic covalent chemistries that can promote closed-loop recyclability and we discuss recent synthetic progress towards incorporating these chemistries into new polymers and existing commodity plastics. Next, we outline how dynamic covalent bonds and polymer network structure influence thermomechanical properties related to application and recyclability, with a focus on predictive physical models that describe network rearrangement. Finally, we examine the potential economic and environmental impacts of dynamic covalent polymeric materials in closed-loop processing using elements derived from techno-economic analysis and life-cycle assessment, including minimum selling prices and greenhouse gas emissions. Throughout each section, we discuss interdisciplinary obstacles that hinder the widespread adoption of dynamic polymers and present opportunities and new directions toward the realization of circularity in polymeric materials.

Instructions on appropriate fasting prior to phlebotomy; effects on patient awareness, preparation, and biochemical parameters.

OBJECTIVES: This study investigated the effect of appropriate pre-phlebotomy instructions on patients' awareness of the need to fast, their fasting status at phlebotomy, and the measurement of specific biochemical analytes and indices. METHODS: While booking their phlebotomy appointments, two-hundred outpatients, with a wide range of pre-existing medical conditions, were recruited and randomly assigned to either control or intervention groups. The control group received no instructions while the intervention group was verbally instructed to fast for precisely 12 h prior to their appointment. Serum samples were collected from participants to quantify common biochemical analytes and serum indices, some of which were known to be influenced by fasting status, such as triglyceride and the lipaemic index. At the same appointment, participants completed a survey assessing their perception of, and adherence to, fasting requirements. RESULTS: In the intervention group, 99% responded that they had fasted before phlebotomy vs. 16% of controls. Subjects stated they fasted for 12 h in 51% of the intervention group and 7% of the controls. Median concentrations for potassium and total bilirubin were statistically, but not clinically, significantly different. In the study, a single patient in the intervention group was found to have a lipaemic sample. CONCLUSIONS: Without instruction, it appears few patients will fast appropriately prior to blood collection. This study suggests that most patients recall and adhere to verbal instructions regarding fasting. Though many in the control group stated they did not fast, triglyceride concentration and lipaemia were not significantly different from the intervention group, and biochemical analyses appear unaffected by fasting status.

Programming Orientation in Liquid Crystalline Elastomers Prepared with Intra-Mesogenic Supramolecular Bonds.

The large, directional stimuli-response of aligned liquid crystalline elastomers (LCEs) could enable functional utility in robotics, medicine, consumer goods, and photonics. The alignment of LCEs has historically been realized via mechanical alignment of a two-stage reaction. Recent reports widely utilize chain extension reactions of liquid crystal monomers (LCM) to form LCEs that are subject to either surface-enforced or mechanical alignment. Here, we prepare LCEs that contain intra-mesogenic supramolecular bonds synthesized via direct free-radical chain transfer photopolymerization processible by a distinctive mechanical alignment mechanism. The LCEs were prepared by the polymerization of a benzoic acid monomer (11OBA), which dimerized to form a liquid crystal monomer, with a diacrylate LCM (C6M). The incorporation of the intra-mesogenic hydrogen bonds increases the achievable nematic order from mechanical programming. Accordingly, LCEs prepared with larger 11OBA concentration exhibit higher magnitude thermomechanical strain values when compared to a LCE containing only covalent bonds. These LCEs can be reprogrammed with heat to return the aligned film to the polydomain state. The LCE can then be subsequently programmed to orient in a different direction. The facile preparation of (re)programmable LCEs with supramolecular bonds opens new avenues for the implementation of these materials as shape deployable elements.

Stiffness anisotropy coordinates supracellular contractility driving long-range myotube-ECM alignment.

In skeletal muscle tissue, injury-related changes in stiffness activate muscle stem cells through mechanosensitive signaling pathways. Functional muscle tissue regeneration also requires the effective coordination of myoblast proliferation, migration, polarization, differentiation, and fusion across multiple length scales. Here, we demonstrate that substrate stiffness anisotropy coordinates contractility-driven collective cellular dynamics resulting in C2C12 myotube alignment over millimeter-scale distances. When cultured on mechanically anisotropic liquid crystalline polymer networks (LCNs) lacking topographic features that could confer contact guidance, C2C12 myoblasts collectively polarize in the stiffest direction of the substrate. Cellular coordination is amplified through reciprocal cell-ECM dynamics that emerge during fusion, driving global myotube-ECM ordering. Conversely, myotube alignment was restricted to small local domains with no directional preference on mechanically isotropic LCNs of same chemical formulation. These findings reveal a role for stiffness anisotropy in coordinating emergent collective cellular dynamics, with implications for understanding skeletal muscle tissue development and regeneration.

Biocatalytic 3D Actuation in Liquid Crystal Elastomers via Enzyme Patterning.

Liquid crystal elastomers (LCEs) are stimuli-responsive materials that undergo large shape transformations after undergoing an order-disorder transition. While shape reconfigurations in LCEs are predominantly triggered by heat, there is a considerable interest in developing highly specific triggers that work at room temperature. Herein, we report the fabrication of biocatalytic LCEs that respond to the presence of urea by covalently immobilizing urease within chemically responsive LCE networks. The hydrogen-bonded LCEs developed in this work exhibited contractile strains of up to 36% upon exposure to a base. Notably, the generation of ammonia by immobilized urease triggered a disruption in the supramolecular network and a large reduction of liquid crystalline order in the films when the LCEs were exposed to urea. This reduction in order was macroscopically translated into a strain response that could be modulated by changing the concentration of urea or exposure time to the substrate. Local control of the mechanical response of the LCE was realized by spatially patterning the enzyme on the surface of the films. Subsequent exposure of enzymatically patterned LCE to urea-triggered 3D shape transformations into a curl, arch, or accordion-like structure, depending on the motif patterned on the film surface. Furthermore, we showed that the presence of salt was critical to prevent bridging of the network by the presence of ammonium ions, thereby enabling such macroscopic 3D shape changes. The large actuation potential of LCEs and the ability to translate the biocatalytic activity of enzymes to macroscopic 3D shape transformations could enable use in applications ranging from cell culture, medicine, or antifouling.

Metastable doubly threaded [3]rotaxanes with a large macrocycle.

Ring size is a critically important parameter in many interlocked molecules as it directly impacts many of the unique molecular motions that they exhibit. Reported herein are studies using one of the largest macrocycles reported to date to synthesize doubly threaded [3]rotaxanes. A large ditopic 46 atom macrocycle containing two 2,6-bis(N-alkyl-benzimidazolyl)pyridine ligands has been used to synthesize several metastable doubly threaded [3]rotaxanes in high yield (65-75% isolated) via metal templating. Macrocycle and linear thread components were synthesized and self-assembled upon addition of iron(ii) ions to form the doubly threaded pseudo[3]rotaxanes that could be subsequently stoppered using azide-alkyne cycloaddition chemistry. Following demetallation with base, these doubly threaded [3]rotaxanes were fully characterized utilizing a variety of NMR spectroscopy, mass spectrometry, size-exclusion chromatography, and all-atom simulation techniques. Critical to the success of accessing a metastable [3]rotaxane with such a large macrocycle was the nature of the stopper group employed. By varying the size of the stopper group it was possible to access metastable [3]rotaxanes with stabilities in deuterated chloroform ranging from a half-life of <1 minute to ca. 6 months at room temperature potentially opening the door to interlocked materials with controllable degradation rates.

Clinical effectiveness of and family experience with telephone consultation in a regional pediatric neurosurgery center in the United Kingdom.

OBJECTIVE: Pediatric neurosurgery outpatient consultation is conducted face-to-face (FTF) conventionally. Reasons for not using telemedicine include the perceived difficulty with obtaining a reliable history and an inability to perform a physical examination. However, FTF consultation can cause distress and inconvenience to the child and family. In 2018, the authors' department piloted a clinical nurse specialist-led telephone consultation (TC) for follow-up appointments. This was extended to the routine neurosurgery clinics in 2020. In this study, the authors evaluate 1) the effectiveness of TC, 2) families' experience with TC compared with traditional FTF appointments, and 3) the factors associated with their preferences. METHODS: In this prospective study using a survey methodology, TCs carried out by 2 consultant neurosurgeons and 1 nurse specialist over 8 weeks were evaluated. Based on clinical background, each patient was assigned to a TC or FTF appointment. Clinical and surgical details and home postal code were recorded. At the end of each TC, the clinician recorded whether the child required an FTF appointment within 3 months. In addition, patients/families answered 1) how the current TC compared with FTF consultation, and 2) their preference of TC or FTF for the next consultation. RESULTS: A total of 114 TCs were included. No child required an FTF appointment within 3 months. Overall, compared with an FTF appointment, the TC was the "same/better/much better" for 101 families (89%), and "worse/much worse" for 13 (11%). Two-thirds of families preferred the next appointment to be a TC. Families attending a TC for new appointments preferred the next appointment to be FTF compared with those attending a follow-up TC (6/8 [75%] vs 31/106 [29%], p = 0.006). A high rating of the current TC was associated with a preference for a TC as the next appointment (p < 0.0001). Families preferring TC over FTF lived farther from the hospital (mean 38 vs 27 km) (p = 0.029). CONCLUSIONS: From the clinicians' perspective, TC is adequate in appropriately selected patients as either the primary mode of consultation or as a triage system. From a service users' perspective, the majority of families felt that the appointment was the same/better than traditional FTF appointments. The findings suggested that 1) new patients should be offered FTF appointments; 2) follow-up TCs should be offered to families when possible; and 3) clinicians should develop their skills in conducting TCs. The authors' results have led to a modification of our algorithm in delivering traditional outpatient service and telemedicine with telephone.

Controlling the Morphology of Dynamic Thia-Michael Networks to Target Pressure-Sensitive and Hot Melt Adhesives.

A series of multistage (pressure-sensitive/hot melt) adhesives utilizing dynamic thia-Michael bonding motifs are reported. The benzalcyanoacetate Michael acceptors used in this work undergo bond exchange under ambient conditions without external catalysis, facilitating pressure-sensitive adhesion. A key feature of this system is the dynamic reaction-induced phase separation that lends reinforcement to the otherwise weakly bonded materials, enabling weak, repeatable pressure-sensitive adhesion under ambient conditions and strong adhesion when processed as a hot melt adhesive. By using different pairs of benzalcyanoacetate cross-linking units, the phase separation characteristics of the adhesives can be directly manipulated, allowing for a tailored adhesive response.

Dynamic reaction-induced phase separation in tunable, adaptive covalent networks.

A series of catalyst-free, room temperature dynamic bonds derived from a reversible thia-Michael reaction are utilized to access mechanically robust dynamic covalent network films. The equilibrium of the thiol addition to benzalcyanoacetate-based Michael-acceptors can be directly tuned by controlling the electron-donating/withdrawing nature of the Michael-acceptor. By modulating the composition of different Michael-acceptors in a dynamic covalent network, a wide range of mechanical properties and thermal responses can be realized. Additionally, the reported systems phase-separate in a process, coined dynamic reaction-induced phase separation (DRIPS), that yields reconfigurable phase morphologies and reprogrammable shape-memory behaviour as highlighted by the heat-induced folding of a predetermined structure.

Strong, Rebondable, Dynamic Cross-Linked Cellulose Nanocrystal Polymer Nanocomposite Adhesives.

A series of strong, rebondable polydisulfide nanocomposite adhesive films have been prepared via the oxidation of a thiol-endcapped semicrystalline oligomer with varying amounts of thiol-functionalized cellulose nanocrystals (CNC-SH). The nanocomposites are designed to have two temperature-sensitive components: (1) the melting of the semicrystalline phase at ca. 70 °C and (2) the inherent dynamic behavior of the disulfide bonds at ca. 150 °C. The utility of these adhesives was demonstrated on different bonding substrates (hydrophilic glass slides and metal), and their bonding at both 80 and 150 °C was examined. In all cases, stronger bonding was achieved at temperatures where the disulfide bonds are dynamic. For high surface energy substrates, such as hydrophilic glass or metal, the adhesive shear strength increases with CNC-SH content, with the 30 wt % CNC-SH composites exhibiting adhesive shear strengths of 50 and 23 MPa for hydrophilic glass and metal, respectively. The effects of contact pressure and time of bonding were also investigated. It was found that ca. 20-30 min bonding time was required to reach maximum adhesion, with adhesives containing higher wt % CNCs requiring longer bonding times. Furthermore, it was found that, in general, an increase in contact pressure results in an increase in the shear strength of the adhesive. The rebonding of the adhesives was demonstrated with little-to-no loss in adhesive shear strength. In addition, the 30 wt % nanocomposite adhesive was compared to some common commercially available adhesives and showed significantly stronger shear strengths when bonded to metal.