Radiographic Outcome and Complication Rate of 34 Graduates After Treatment With Vertical Expandable Prosthetic Titanium Rib (VEPTR): A Single Center Report.

BACKGROUND: The final strategy for graduates from growth-sparing surgery is challenging. The purpose of this study was to evaluate the radiographic outcome and complications of patients with early onset scoliosis (EOS) who have graduated from vertical expandable prosthetic titanium rib (VEPTR) treatment, either undergoing final fusion surgery or following a nonfusion approach. METHODS: Final treatment for VEPTR graduates was divided in "VEPTR in situ without final fusion," "removal of VEPTR without final fusion," and "removal of VEPTR with instrumented final fusion." Radiographic evaluations included main coronal Cobb angle and main kyphosis pre and post VEPTR implantation, at the end of implant lengthening, after final fusion (if applicable), and at latest follow-up. Complications during VEPTR treatment and in case of final fusion were reported. RESULTS: In total, 34 VEPTR graduates were included; 17 underwent final fusion surgery, and 17 followed a nonfusion strategy. Average coronal Cobb angle before VEPTR implantation was 70±23 degrees (range, 21 to 121 degrees), and 65±22 degrees (range, 17 to 119 degrees) at latest follow-up. Average main kyphosis angle was 53±27 degrees (range, 6 to 137 degrees) before VEPTR, and 69±34 degrees (range, 10 to 150 degrees) at latest follow-up. There was a 41% complication rate with final fusion surgery. CONCLUSIONS: There is a high complication rate during VEPTR treatment and with final fusion surgery. The stiffness of the spine and thorax allow for only limited correction when performing a final instrumented spondylodesis. Avoiding final fusion may be a viable alternative in case of good coronal and sagittal alignment. LEVEL OF EVIDENCE: Level IV-therapeutic.

Bacterial colonization of VEPTR implants under repeated expansions in children with severe early onset spinal deformities.

PURPOSE: Historically, severe spinal and thoracic deformities in children were treated with early long spinal fusions. This prevented further growth of the spine and thorax and often led to small stiff thoraces. Therefore, growth-retaining implants, like vertical expandable titanium ribs (VEPTR), were developed to stimulate thoracic and spinal growth. To accommodate growth, these implants have to be expanded every 6 months. Infection rates of up to 2 % per procedure are reported. Exchange of implant parts allows analyzing the development of implant-related infections and subclinical colonizations. METHODS: In this prospective study, all patients undergoing repeat VEPTR expansion procedures at our institution were included. Preoperatively, clinical signs of infection were documented, and blood samples were taken. The removed implants were treated by sonication and microbiologically analyzed. The clinical follow-up was documented. RESULTS: From January 2009 to May 2012, 39 children with 163 re-operations were included. Four of the 39 patients (10 %) developed clinical apparent infections and had implant removal. These were excluded and analyzed separately. Of 144 procedures, implant parts were eligible for analysis. Implant colonization was detected by sonication in 24 of 144 (16 %) operations in 18 out of 39 (46 %) patients. Repeated detection occurred in 5 (14 %) patients. No risk factors for colonization could be identified. CONCLUSION: The rate of implant colonization is 4.5 times higher than the rate of manifest infections in VEPTR patients. Colonization may lead to a manifest infection over time. The knowledge of persistent implant colonization may change the treatment algorithm in patients with growth-retaining implants.

Patient-specific spinal stiffness in AIS: a preoperative and noninvasive method.

INTRODUCTION: The clinical tests currently used to assess spinal biomechanics preoperatively are unable to assess true mechanical spinal stiffness. They rely on spinal displacement without considering the force required to deform a patient's spine. We propose a preoperative method for noninvasively quantifying the three-dimensional patient-specific stiffness of the spines of adolescent idiopathic scoliosis patients. METHODS: The technique combines a novel clinical test with numerical optimization of a finite element model of the patient's spine. RESULTS: A pilot study conducted on five patients showed that the model was able to provide accurate 3D reconstruction of the spine's midline and predict the spine's stiffness for each patient in flexion, bending, and rotation. Statistically significant variation of spinal stiffness was observed between the patients. CONCLUSION: This result confirms that spinal biomechanics is patient-specific, which should be taken into consideration to individualize surgical treatment.

A new tool based on two micromanipulators facilitates the handling of ultrathin cryosection ribbons.

A close to native structure of bulk biological specimens can be imaged by cryo-electron microscopy of vitreous sections (CEMOVIS). In some cases structural information can be combined with X-ray data leading to atomic resolution in situ. However, CEMOVIS is not routinely used. The two critical steps consist of producing a frozen section ribbon of a few millimeters in length and transferring the ribbon onto an electron microscopy grid. During these steps, the first sections of the ribbon are wrapped around an eyelash (unwrapping is frequent). When a ribbon is sufficiently attached to the eyelash, the operator must guide the nascent ribbon. Steady hands are required. Shaking or overstretching may break the ribbon. In turn, the ribbon immediately wraps around itself or flies away and thereby becomes unusable. Micromanipulators for eyelashes and grids as well as ionizers to attach section ribbons to grids were proposed. The rate of successful ribbon collection, however, remained low for most operators. Here we present a setup composed of two micromanipulators. One of the micromanipulators guides an electrically conductive fiber to which the ribbon sticks with unprecedented efficiency in comparison to a not conductive eyelash. The second micromanipulator positions the grid beneath the newly formed section ribbon and with the help of an ionizer the ribbon is attached to the grid. Although manipulations are greatly facilitated, sectioning artifacts remain but the likelihood to investigate high quality sections is significantly increased due to the large number of sections that can be produced with the reported tool.

Axial suspension test to assess pre-operative spinal flexibility in patients with adolescent idiopathic scoliosis.

INTRODUCTION: An accurate description of the biomechanical behavior of the spine is crucial for the planning of scoliotic surgical correction as well as for the understanding of degenerative spine disorders. The current clinical assessments of spinal mechanics such as side-bending or fulcrum-bending tests rely on the displacement of the spine observed during motion of the patient. Since these tests focused solely on the spinal kinematics without considering mechanical loads, no quantification of the mechanical flexibility of the spine can be provided. METHODS: A spinal suspension test (SST) has been developed to simultaneously monitor the force applied on the spine and the induced vertebral displacements. The system relies on cervical elevation of the patient and orthogonal radiographic images are used to measure the position of the vertebras. The system has been used to quantify the spinal flexibility on five AIS patients. RESULTS: Based on the SST, the overall spinal flexibility varied between 0.3 °/Nm for the patient with the stiffer curve and 2 °/Nm for the less rigid curve. A linear correlation was observed between the overall spinal flexibility and the change in Cobb angle. In addition, the segmental flexibility calculated for five segments around the apex was 0.13 ± 0.07 °/Nm, which is similar to intra-operative stiffness measurements previously published. CONCLUSIONS: In summary, the SST seems suitable to provide pre-operative information on the complex functional behavior and stiffness of spinal segments under physiological loading conditions. Such tools will become increasingly important in the future due to the ever-increasing complexity of the surgical instrumentation and procedures.

Diagnostic and therapeutic strategies in early onset scoliosis: A current concept review.

Substantial advances in the treatment of early onset scoliosis (EOS) over the past two to three decades have resulted in significant improvements in health-related quality of life of affected children. In addition to classifications that address the marked heterogeneity of this patient population, increasing understanding of the natural history of the disease, and new implants and treatment techniques have resulted in innovations unlike any other area of pediatric orthopedics. The growing understanding of the interaction between spinal and thoracic growth, as well as dependent lung maturation, has had a lasting impact on the treatment strategy of this potentially life-threatening disease. The previous treatment approach with early corrective fusion gave way to a growth-friendly concept. Despite the steady development of new growth-friendly surgical treatment options, whose efficacy still needs to be validated, as well as a revival of conservative growth control with serial casts and/or braces, the psychosocial burden of the long lasting and complication-prone treatments remains high. As a consequence, EOS still represents one of the greatest pediatric orthopedic challenges.

Safety and efficacy of growth-friendly instrumentation for early-onset scoliosis in patients with spinal muscular atrophy type 1 in the disease-modifying treatment era.

Purpose: To evaluate the safety of growth-friendly instrumentation for early-onset scoliosis (EOS) in patients with spinal muscular atrophy (SMA) type 1 who received disease-modifying treatment (DMT) and analyze short-term efficacy. Methods: Retrospective search was conducted between 2017 and 2023. Patients with genetically confirmed SMA type 1 who were surgically treated for spinal deformity and receiving DMTs (nusinersen, risdiplam, or onasemnogene abeparvovec) were included. SMA types 2 and 3 and patients who do not receive DMTs were excluded. Clinical and radiographic data were collected at preoperative, postoperative, and latest follow-up visits. Results: Twenty-eight patients (mean follow-up: 16 months (range 2-41)) were included. The mean age at surgery was 60 months (range 29-96). Fifteen were treated with dual magnetically controlled growing rods (MCGR), four with unilateral MCGR and a contralateral guided growth system, three with Vertical Expandable Prosthetic Titanium Rib (VEPTR®) implants, five with self-distracting systems, and one with traditional dual growing rods. The mean amount of correction was 57% (44°± 17) for scoliosis and 83% (13°± 11) for pelvic obliquity. The mean T1-12 height gain during surgery was 31 mm (±16 mm), while the mean T1 S1 height gain was 51 mm (±24 mm), and instrumented growth was observed during follow-up. Five patients (18%) developed six serious adverse events: three surgical site infections, two anchor failures, and one rod fracture, and all required unplanned reoperations. No neurologic complication, difficulty during nusinersen injections, or respiratory decline was recorded. Conclusion: We report that spinal deformity in this population can be safely treated with growth-friendly instrumentation, with similar complication rates when compared with SMA type 2.

The global impact of the COVID-19 pandemic on pediatric spinal care: A multi-centric study.

Background: The COVID-19 pandemic has affected healthcare worldwide since December 2019. We aimed to identify the effect of the COVID-19 pandemic on outpatient clinic and surgical volumes and peri-operative complications for pediatric spinal deformities patients. Methods: In this multi-center retrospective study, outpatient visits (in-person and virtual care) and pediatric spine surgeries volumes in four high-volume pediatric spine centers were compared between March and December 2019 and the same period in 2020. Peri-operative complications were collected and compared in the same periods. Descriptive statistics were calculated, and comparative analyses were performed. Results: During the 2020 study period, the outpatient visit (in-person and virtual care) volume decreased during local lockdown periods by 71% for new patients (p < 0.001) and 53% for returning patients (p = 0.03). Overall, for 2020, there was a 20% reduction in new patients (p = 0.001) and 21% decrease in returning patients (p < 0.001). During the pandemic, there was also 20% less overall surgical volume of adolescent idiopathic scoliosis (AIS) patients undergoing primary posterior spinal fusion, with a 70% reduction during lockdown times (p < 0.001). Complication rate and profile were similar between periods. Conclusion: There was a significant decrease in outpatient pediatric spine outpatient visits, particularly new patients, which may increase the proportion of pediatric patients with spinal deformities that present late, meeting surgical indication. This, in combination with the reduction in surgical volume of AIS over the first year of the pandemic, could result in an extended waitlist for surgeries during years to come. Complication rate was similar for both periods, suggesting it is safe to continue elective pediatric spine surgery even in a time of a pandemic. Level of evidence: level IV.

Fine structure of hippocampal mossy fiber synapses following rapid high-pressure freezing.

Synapses of hippocampal neurons play important roles in learning and memory processes and are involved in aberrant hippocampal function in temporal lobe epilepsy. Major neuronal types in the hippocampus as well as their input and output synapses are well known, but it has remained an open question to what extent conventional electron microscopy (EM) has provided us with the real appearance of synaptic fine structure under in vivo conditions. There is reason to assume that conventional aldehyde fixation and dehydration lead to protein denaturation and tissue shrinkage, likely associated with the occurrence of artifacts. However, realistic fine-structural data of synapses are required for our understanding of the transmission process and for its simulation. Here, we used high-pressure freezing and cryosubstitution of hippocampal tissue that was not subjected to aldehyde fixation and dehydration in ethanol to monitor the fine structure of an identified synapse in the hippocampal CA3 region, that is, the synapse between granule cell axons, the mossy fibers, and the proximal dendrites of CA3 pyramidal neurons. Our results showed that high-pressure freezing nicely preserved ultrastructural detail of this particular synapse and allowed us to study rapid structural changes associated with synaptic plasticity.

Traditional T1-S1 Measurement of the Spinal Length on X-ray Images Does Not Correlate With the True Length of the Spine.

BACKGROUND: The T1-S1 distance to evaluate spinal length is traditionally measured as a straight line on an anteroposterior radiograph. However, this method may not reflect the true 3-dimensional (3D) spinal length. The objective of the study was to evaluate the difference between the traditional T1-S1 measurement and a 3D reconstruction from standard x-ray imaging. METHODS: Radiological assessment and 3D reconstruction of spinal length in pediatric patients with various spine deformities. The 3D reconstruction derived from standard biplanar spine x-ray images using a specialized but free available software and calibration device. Direct comparison of length, intraobserver variance for repeated measurements, as well as interobserver correlation for both measurement methods and between different levels of training were evaluated. Furthermore, the influence on spinal length by the degree of spinal deformity as well as other factors was analyzed. RESULTS: A total of 39 x-ray images from 35 patients at a mean age of 15.4 years (8.9-26.8 years) were evaluated. There was excellent agreement for intra- and interobserver correlation for both measurement techniques. Spinal length assessed using 3D reconstruction was significantly longer compared with the traditional T1-S1 distance, on average 2.7 cm (0.5-6.1 cm). There was also a significant positive correlation between the maximum extent of the deformity and the difference in spinal length. CONCLUSIONS: Traditional T1-S1 distance significantly underestimates the true length of the spine. A 3D measurement reflects the real length of the spine more adequately. CLINICAL RELEVANCE: Such information is relevant to the treating spine surgeon when planning or assessing therapeutic measures, especially in advanced deformities.

Eliminating exposure to aqueous solvents is necessary for the early detection and ultrastructural elemental analysis of sites of calcium and phosphorus enrichment in mineralizing UMR106-01 osteoblastic cultures.

The mechanism underlying the mineralization of bone is well studied and yet it remains controversial. Inherent difficulties of imaging mineralized tissues and the aqueous solubility of calcium and phosphate, the 2 ions which combine to form bone mineral crystals, limit current analyses of labile diffusible, amorphous, and crystalline intermediates by electron microscopy. To improve the retention of calcium and phosphorus, we developed a pseudo nonaqueous processing approach and used it to characterize biomineralization foci, extracellular sites of hydroxyapatite deposition in osteoblastic cell cultures. Since mineralization of UMR106-01 osteoblasts is temporally synchronized and begins 78 h after plating, we used these cultures to evaluate the effectiveness of our method when applied to cells just prior to the formation of the first mineral crystals. Our approach combines for the first time 3 well-established methods with a fourth one, i.e. dry ultrathin sectioning. Dry ultrathin sectioning with an oscillating diamond knife was used to produce electron spectroscopic images of mineralized biomineralization foci which were high-pressure frozen and freeze substituted. For comparison, cultures were also treated with conventional processing and wet sectioning. The results show that only the use of pseudo nonaqueous processing was able to detect extracellular sites of early calcium and phosphorus enrichment at 76 h, several hours prior to detection of mineral crystals within biomineralization foci.

Investigating the interaction of cellulose nanofibers derived from cotton with a sophisticated 3D human lung cell coculture.

Cellulose nanofibers are an attractive component of a broad range of nanomaterials. Their intriguing mechanical properties and low cost, as well as the renewable nature of cellulose make them an appealing alternative to carbon nanotubes (CNTs), which may pose a considerable health risk when inhaled. Little is known, however, concerning the potential toxicity of aerosolized cellulose nanofibers. Using a 3D in vitro triple cell coculture model of the human epithelial airway barrier, it was observed that cellulose nanofibers isolated from cotton (CCN) elicited a significantly (p < 0.05) lower cytotoxicity and (pro-)inflammatory response than multiwalled CNTs (MWCNTs) and crocidolite asbestos fibers (CAFs). Electron tomography analysis also revealed that the intracellular localization of CCNs is different from that of both MWCNTs and CAFs, indicating fundamental differences between each different nanofibre type in their interaction with the human lung cell coculture. Thus, the data shown in the present study highlights that not only the length and stiffness determine the potential detrimental (biological) effects of any nanofiber, but that the material used can significantly affect nanofiber-cell interactions.

Conservative treatment and outcome of upper cervical spine fractures in young children: A STROBE-compliant case series.

ABSTRACT: Cervical spine (C-spine) fractures in young children are very rare, and little information on treatment modalities and functional, radiographic, and patient-reported outcome exists. In this 2-center, retrospective case series, we assessed subjective and functional mid-term outcomes in children aged ≤5 years whose C-spine fractures were treated nonoperatively.Between 2000 and 2018, 6 children (median age at injury: 23.5 months; range: 16-31 months) with C1 or C2 injuries were treated with Minerva cast/brace or soft collar brace at 1 of the 2 study centers. Two patients suffered C1 fractures, and 4 patients had lysis of the odontoid synchondrosis. Overall, 3 children had sustained polytrauma. One child died due to the consequences of massive head injury.For the primary outcome parameter, we recorded subjective symptoms such as pain and functional restrictions due to the sequelae of C-spine injuries at follow-up.Based on medical records, we also assessed the causes of injury, diagnostic procedures, treatments and complications, and time to fracture consolidation.Median follow-up of the 5 surviving children was 51 months (range: 36-160 months). At the latest follow-up, 4 of 5 children did not complain of any pain. One child who sustained an open head injury in combination with a subluxation of the odontoid and undisplaced fracture of the massa lateralis reported occasional headache. All patients experienced complete fracture healing and normal range of motion of the cervical spine.Median duration of cast/brace treatment was 8.5 weeks. Fracture healing was confirmed by computed tomography in all patients.All C-spine injuries were managed with either Minerva cast/Halo brace or soft collar brace without complications.In our retrospective case series, nonoperative treatment of atlas fractures and dislocations or subluxations of the odontoid in young children using Minerva casts or prefabricated Halo braces resulted in good subjective and functional outcomes at mid-term. We observed no complications of conservative treatment of C1 and C2 injuries in young children.

Lamellar body ultrastructure revisited: high-pressure freezing and cryo-electron microscopy of vitreous sections.

Lamellar bodies are the storage sites for lung surfactant within type II alveolar epithelial cells. The structure-function models of lamellar bodies are based on microscopic analyses of chemically fixed tissue. Despite available alternative fixation methods that are less prone to artifacts, such as cryofixation by high-pressure freezing, the nature of the lung, being mostly air filled, makes it difficult to take advantage of these improved methods. In this paper, we propose a new approach and show for the first time the ultrastructure of intracellular lamellar bodies based on cryo-electron microscopy of vitreous sections in the range of nanometer resolution. Thus, unspoiled by chemical fixation, dehydration and contrasting agents, a close to native structure is revealed. Our approach uses perfluorocarbon to substitute the air in the alveoli. Lung tissue was subsequently high-pressure frozen, cryosectioned and observed in a cryo-electron microscope. The lamellar bodies clearly show a tight lamellar morphology. The periodicity of these lamellae was 7.3 nm. Lamellar bifurcations were observed in our cryosections. The technical approach described in this paper allows the examination of the native cellular ultrastructure of the surfactant system under near in vivo conditions, and therefore opens up prospectives for scrutinizing various theories of lamellar body biogenesis, exocytosis and recycling.

Long term outcome of vertical expandable prosthetic titanium rib treatment in children with early onset scoliosis.

The vertical expandable prosthetic titanium rib (VEPTR) device was originally developed for the treatment of thoracic insufficiency syndrome with the aim of improving respiratory function of affected patients. Although clinically obvious, the changes in pulmonary function of VEPTR-treated patients are difficult to assess when using common lung function tests, and newer techniques based on functional magnetic resonance imaging (MRI) are currently being evaluated. The potential of improving lung function and simultaneously controlling the spinal deformity has continuously broadened the spectrum of indications for VEPTR, not least due to the frequent reports of complications with spine-based traditional growing rods (tGR). However, the initial enthusiasm of spine-sparing deformity correction has progressively subsided with the increasing number of reports on complications, including the detection of extraspinal ossifications along the implants and across ribs. The avoidance of repetitive surgical implant lengthening with the availability of motorized distraction-based implants has further diminished the use of VEPTR, especially in the absence of volume-depletion deformities of the thorax. In view of the still scarce reporting on the ultimate strategy of VEPTR treatment and the lack of long-term follow-up of patients receiving growth-sparing surgery, only limited conclusions can be drawn so far. Based on the available reports, however, the intended deformity corrections with final fusion surgeries can be achieved to a rather limited extent, while the complication and reoperation rates are still very high.

Spinal Surgery With Electrically Evoked Potential Monitoring and Monopolar Electrocautery: Is Prior Removal of a Cochlear Implant Necessary?

: Transcranial electric stimulation to generate motor evoked potentials in lower limb muscles is the standard technique used to monitor spinal cord efferent pathways during surgical correction for spinal deformities. Monopolar electrical cauterization is also used by default in the thoracic and lumbar area of the spine during this kind of surgery to prevent major blood loss. Owing to the high levels of current used, both techniques are considered contraindicative if the patient has a cochlear implant (CI). Here, we present a CI patient who underwent corrective spinal fusion surgery for a severe kyphoscoliotic spinal deformity on whom both techniques were used without any negative effects on the CI function. A major improvement in sagittal body balance was achieved with no loss in implant-aided hearing levels. These results add to reports that CI manufactures should review their evidence underlying recommendations that transcranial electric stimulation and upper thoracic monopolar electrical cauterization are high risk for CI users, possibly initiating verification studies.

Reprint of "Stereology meets electron tomography: towards quantitative 3D electron microscopy" [J. Struct. Biol. 159 (2007) 443-450].

Stereological tools are the gold standard for accurate (i.e., unbiased) and precise quantification of any microscopic sample. The past decades have provided a broad spectrum of tools to estimate a variety of parameters such as volumes, surfaces, lengths, and numbers. Some of them require pairs of parallel sections that can be produced by either physical or optical sectioning, with optical sectioning being much more efficient when applicable. Unfortunately, transmission electron microscopy could not fully profit from these riches, mainly because of the large depth of field. Hence, optical sectioning was a long-time desire for electron microscopists. This desire was fulfilled with the development of electron tomography that yield stacks of slices from electron microscopic sections. Now, parallel optical slices of a previously unimagined small thickness (2-5nm axial resolution) can be produced. These optical slices minimize problems related to overprojection effects, and allow for direct stereological analysis, e.g., volume estimation with the Cavalieri principle and number estimation with the optical disector method. Here, we demonstrate that the symbiosis of stereology and electron tomography is an easy and efficient way for quantitative analysis at the electron microscopic level. We call this approach quantitative 3D electron microscopy.

Cryoultramicrotomy: cryoelectron microscopy of vitreous sections.

Cryoultramicrotomy allows the sectioning of vitrified biological samples. These biological samples are preserved at the atomic level and represent the real structure at the moment of freezing. Cryoultramicrotomy produces ultra-thin cryosections that are investigated in a cryoelectron microscope. The necessity of working during the whole preparation at temperatures less than -140 degrees C results in some difficulties, including the cryosection transfer from the knife-edge to the electron microscropy grid; the grid handling in the cryochamber and the grid transfer into the cryoholder of the electron microscope. Furthermore, ice crystal contamination (from air humidity) can obscure the structures of interest in the sections. It is mainly know-how and experience that will prevent the contamination of ice crystals and the recrystallization of the sections during the manipulations. Here, we describe the tips, tricks, the tools, and methods that help to overcome these burdens and pave the path for successful cryoultramicrotomy.

Electron energy-loss spectroscopy as a tool for elemental analysis in biological specimens.

A transmission electron microscope (TEM) accessory, the energy filter, enables the establishment of a method for elemental microanalysis, the electron energy-loss spectroscopy (EELS). In conventional TEM, unscattered, elastic, and inelastic scattered electrons contribute to image information. Energy-filtering TEM (EFTEM) allows elemental analysis at the ultrastructural level by using selected inelastic scattered electrons. EELS is an excellent method for elemental microanalysis and nanoanalysis with good sensitivity and accuracy. However, it is a complex method whose potential is seldom completely exploited, especially for biological specimens. In addition to spectral analysis, parallel-EELS, we present two different imaging techniques in this chapter, namely electron spectroscopic imaging (ESI) and image-EELS. We aim to introduce these techniques in this chapter with the elemental microanalysis of titanium. Ultrafine, 22-nm titanium dioxide particles are used in an inhalation study in rats to investigate the distribution of nanoparticles in lung tissue.