The effect of long-term alendronic acid treatment on Modic changes in the lumbar spine: a gender and age-matched study.

BACKGROUND: Low back pain (LBP) affects a significant proportion of the adult population. Potent anti-resorptive drugs such as intravenous zoledronic acid have been demonstrated to reduce Modic changes (MCs) upon magnetic resonance imaging (MRI) of the spine and concomitantly decrease associated LBP. It is uncertain whether oral alendronic acid has a similar effect. METHODS: 82 subjects were recruited in this case-control study. Treatment subjects (n = 41) received oral alendronic acid treatment for at least 1-year and were matched by gender and age (± 2) to control subjects (n = 41) not receiving any anti-osteoporotic medication. The prevalence, type, and extent of MCs were quantified upon T1 and T2-weighted MRIs of the lumbosacral spine. RESULTS: Treatment subjects received oral alendronic acid for 124.0 ± 62.1 weeks at the time of MRI assessment and exhibited a lower prevalence of MCs over the lumbosacral spine (18/41 vs. 30/41, p < 0.001) as compared to control subjects. Amongst both groups, type 2 MCs were predominant. Quantification of type 2 MCs in treatment subjects revealed a significant reduction in area (113 ± 106 mm2 vs. 231 ± 144 mm2, p < 0.01) and volume (453 ± 427 mm3 vs. 925 ± 575 mm3, p < 0.01) affected by type 2 MCs in comparison to matched controls. CONCLUSION: Oral alendronic acid may be useful in the treatment of MC-associated LBP in patients with concomitant osteoporosis.

Paired and matched analysis of neurological outcomes in revision surgery for cervical myelopathy following delayed neurological decline.

Background: Delayed neurological decline may be experienced following successful decompression surgery for cervical myelopathy. Our objective was to analyze neurological recovery upon revision surgery with relation to the index procedure and a matched control. Methods: Fourteen patients underwent both primary and revision decompression at a single academic center. Peri-operative clinical, radiological, and surgical details were retrieved. Neurological outcomes [change in modified Japanese Orthopedic Association (mJOA), recovery ratio] following the second surgery were compared to (I) the primary operation and (II) a control subject receiving primary decompression matched for gender, age, mJOA score, and surgical approach. The minimum clinically important difference (MCID) in mJOA score was set at 2.5. Results: Revision decompressions were performed 6.8±4.2 years following the index surgery, when patients were 61.4±11.0 years of age. An increase in mJOA score of 2.7±2.0 following revision surgery was similar to that achieved after the primary operation (2.2±2.1, P=0.616). A recovery ratio of 38.1%±25.4% upon revision compared favorably to that following the primary operation (35.0%±37.4%, P=0.867). Non-inferiority testing between revision surgery and the first operation (P=0.02) demonstrated a similar capacity to achieve the MCID as did comparison with matched subjects (P<0.01). Conclusions: Patients were able to make up for lost neurological gains following revision surgery. Careful selection of cases for revision likely facilitated recovery. Recovery trajectories should be consolidated upon larger sample sizes allowing for identification of prognostic factors.

Incidence of back pain from initial presentation to 3 years of follow-up in subjects with untreated adolescent idiopathic scoliosis.

BACKGROUND: Although back pain may be present in subjects with adolescent idiopathic scoliosis (AIS), its natural history is unknown. Therefore, this study evaluated the incidence of back pain in scoliotic adolescents longitudinally. METHODS: This retrospective analysis examined prospectively collected pain subscale data of the Scoliosis Research Society questionnaire between the initial presentation and up to 3 years of follow-up. Consecutive subjects with AIS aged 10-18 at baseline managed by observation within the study period were included. Study subjects with at least one time point of follow-up data were considered. Alternatively, a group with physiotherapy-treated was also included for comparison. RESULTS: We enrolled 428 subjects under observation. The incidence of back pain among study subjects was 14.7%, 18.8%, and 19.0% for the first year, second year, and third year of follow-up, respectively. Most experienced mild pain (1 out of 5 points) throughout the study. Neither incidence nor intensity of pain significantly differed between subjects under observation and received physiotherapy. Additionally, study subjects with a new onset of back pain had poorer function, self-image, and mental health scores than those without pain. CONCLUSION: We investigated the incidence of back pain longitudinally in subjects suffering from AIS. Further validation of the current results is warranted.

Clinical characteristics, densitometric parameters and outcomes of patients with atypical femoral fractures related to bisphosphonate treatment for osteoporosis.

PURPOSE: We described the clinical and densitometric characteristics and treatment outcomes of patients who developed atypical femoral fractures (AFF) while on bisphosphonate for osteoporosis. METHODS: We performed a retrospective cohort study including all adults aged ≥50 years who developed AFF while on bisphosphonates between 1 January 2008 and 31 December 2020, and subsequently managed in the Osteoporosis Centre at Queen Mary Hospital in Hong Kong. A control group of patients who developed fragility hip fractures while on bisphosphonates in the same period was included for comparison. We compared the clinical and densitometric characteristics between the two groups, and described the clinical outcomes for the AFF group. RESULTS: In total, 75 patients were included (AFF: n = 35; fragility hip fracture: n = 40). All were related to oral bisphosphonates. The AFF group was characterised by a longer duration of bisphosphonate use (median of 5 years), higher bone mineral density (BMD) and more acute neck-shaft angle (all p < 0.05). Following AFF, 8 patients (22.9%) did not receive any subsequent bone-active agents: due to refusal to use an injectable, or BMD out of osteoporotic range. Most of those who received bone-active agents were given teriparatide, followed by raloxifene, and achieved stable BMD. However, subsequent fragility risk remained high. Nonetheless, AFF did not confer excess morbidity and mortality. CONCLUSION: AFF was characterised by usually long duration of bisphosphonate use, higher BMD and more acute neck-shaft angle. AFF did not confer significant impairment in mobility or mortality. Nonetheless, further research work is necessary to optimise bone health among patients who develop AFF.

Drain blockage by topical vancomycin powder-a case report of a potentially catastrophic complication in spine surgery.

Background: There is evidence that application of vancomycin powder reduces the incidence of surgical site infection (SSI) and is also effective for the treatment of infections requiring surgical debridement. The use of intrawound vancomycin powder is therefore becoming prevalent. Surgical drain occlusion by antibiotic powder is a potentially serious complication that has yet to be reported in the literature. Case Description: We describe a 62-year-old female with L4/5 spondylodiscitis as well as an L1-S1 epidural abscess who presented with back pain, lower limb numbness and weakness. Urgent surgical drainage was performed via a hemilaminectomy and L4/5 diskectomy. Drain output was absent for the first 36 hours post-op, and upon inspection and disconnection of the distal drain tubing, vancomycin powder residue was noted to be deposited within the lumen and connection point to cause complete obstruction. Following tubing exchange, drainage output resumed. The patient experienced relief of her back and leg symptoms after surgery as well as a normalization of her inflammatory markers upon receiving a course of intravenous (IV) antibiotics. Conclusions: Drain occlusion from antibiotic powder may be catastrophic following spine surgery due to the risk of epidural hematoma formation followed by compression of neural elements. We review the physicochemical properties of vancomycin powder and discuss ways to prevent this complication from occurring.

Blood-spinal cord barrier disruption in degenerative cervical myelopathy.

Degenerative cervical myelopathy (DCM) is the most prevalent cause of spinal cord dysfunction in the aging population. Significant neurological deficits may result from a delayed diagnosis as well as inadequate neurological recovery following surgical decompression. Here, we review the pathophysiology of DCM with an emphasis on how blood-spinal cord barrier (BSCB) disruption is a critical yet neglected pathological feature affecting prognosis. In patients suffering from DCM, compromise of the BSCB is evidenced by elevated cerebrospinal fluid (CSF) to serum protein ratios and abnormal contrast-enhancement upon magnetic resonance imaging (MRI). In animal model correlates, there is histological evidence of increased extravasation of tissue dyes and serum contents, and pathological changes to the neurovascular unit. BSCB dysfunction is the likely culprit for ischemia-reperfusion injury following surgical decompression, which can result in devastating neurological sequelae. As there are currently no therapeutic approaches specifically targeting BSCB reconstitution, we conclude the review by discussing potential interventions harnessed for this purpose.

Revealing the developmental origin and lineage predilection of neural progenitors within human bone marrow via single-cell analysis: implications for regenerative medicine.

BACKGROUND: Human bone marrow stromal cells (BMSCs) are an easily accessible and expandable progenitor population with the capacity to generate neural cell types in addition to mesoderm. Lineage tracing studies in transgenic animals have indicated Nestin + BMSCs to be descended from the truncal neural crest. Single-cell analysis provides a means to identify the developmental origin and identity of human BMSC-derived neural progenitors when lineage tracing remains infeasible. This is a prerequisite towards translational application. METHODS: We attained transcriptomic profiles of embryonic long bone, adult human bone marrow, cultured BMSCs and BMSC-derived neurospheres. Integrated scRNAseq analysis was supplemented by characterization of cells during culture expansion and following provision of growth factors and signalling agonists to bias lineage. RESULTS: Reconstructed pseudotime upon the integrated dataset indicated distinct neural and osteogenic differentiation trajectories. The starting state towards the neural differentiation trajectory consisted of Nestin + /MKI67 + BMSCs, which could also be diverted towards the osteogenic trajectory via a branch point. Nestin + /PDGFRA + BMSCs responded to neurosphere culture conditions to generate a subpopulation of cells with a neuronal phenotype according to marker expression and gene ontogeny analysis that occupied the end state along the neural differentiation trajectory. Reconstructed pseudotime also revealed an upregulation of BMP4 expression during culture of BMSC-neurospheres. This provided the rationale for culture supplementation with the BMP signalling agonist SB4, which directed progenitors to upregulate Pax6 and downregulate Nestin. CONCLUSIONS: This study suggested BMSCs originating from truncal neural crest to be the source of cells within long bone marrow possessing neural differentiation potential. Unravelling the transcriptomic dynamics of BMSC-derived neural progenitors promises to enhance differentiation efficiency and safety towards clinical application in cell therapy and disease modelling.

An intelligent composite model incorporating global / regional X-rays and clinical parameters to predict progressive adolescent idiopathic scoliosis curvatures and facilitate population screening.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) affects up to 5% of the population. The efficacy of school-aged screening remains controversial since it is uncertain which curvatures will progress following diagnosis and require treatment. Patient demographics, vertebral morphology, skeletal maturity, and bone quality represent individual risk factors for progression but have yet to be integrated towards accurate prognostication. The objective of this work was to develop composite machine learning-based prediction model to accurately predict AIS curves at-risk of progression. METHODS: 1870 AIS patients with remaining growth potential were identified. Curve progression was defined by a Cobb angle increase in the major curve of ≥6° between first visit and skeletal maturity in curves that exceeded 25°. Separate prediction modules were developed for i) clinical data, ii) global/regional spine X-rays, and iii) hand X-rays. The hand X-ray module performed automated image classification and segmentation tasks towards estimation of skeletal maturity and bone mineral density. A late fusion strategy integrated these domains towards the prediction of progressive curves at first clinic visit. FINDINGS: Composite model performance was assessed on a validation cohort and achieved an accuracy of 83.2% (79.3-83.6%, 95% confidence interval), sensitivity of 80.9% (78.2-81.9%), specificity of 83.6% (78.8-84.1%) and an AUC of 0.84 (0.81-0.85), outperforming single modality prediction models (AUC 0.65-0.78). INTERPRETATION: The composite prediction model achieved a high degree of accuracy. Upon incorporation into school-aged screening programs, patients at-risk of progression may be prioritized to receive urgent specialist attention, more frequent follow-up, and pre-emptive treatment. FUNDING: Funding from The Society for the Relief of Disabled Children was awarded to GKHS.

Clinical Reasoning in Medical Education: A Primer for Medical Students.

Issue: Proper application of clinical reasoning is a prerequisite toward safe practice. Formal instruction on clinical reasoning remains lacking in medical curricula, especially in preparation for the transition from pre-clinical to clinical years. Evidence: Although medical educators have published abundantly on clinical reasoning and acknowledge this to be an essential part of medical education, there remains a global curricular deficiency in developing this skillset. Here we introduce the reader to clinical reasoning frameworks with an emphasis upon practical application. Our focus is upon medical students transitioning from pre-clinical to clinical years of medical school who tend to be overwhelmed with facts but have limited sense of diagnostic approaches due to lack of instruction. Implications: In understanding systematic approaches to clinical reasoning of relevance to medical diagnosis, students will be able to process knowledge in a clinically relevant and discriminatory manner to facilitate problem solving. Upon internship and residency, they will be better prepared for self-learning and reflection as they understand how to hone their capability for diagnosis and management. Medical educators need to acknowledge that clinical reasoning is a practical academic discipline requiring greater curricular emphasis.

IPSC-Derived Sensory Neurons Directing Fate Commitment of Human BMSC-Derived Schwann Cells: Applications in Traumatic Neural Injuries.

The in vitro derivation of Schwann cells from human bone marrow stromal cells (hBMSCs) opens avenues for autologous transplantation to achieve remyelination therapy for post-traumatic neural regeneration. Towards this end, we exploited human induced pluripotent stem-cell-derived sensory neurons to direct Schwann-cell-like cells derived from among the hBMSC-neurosphere cells into lineage-committed Schwann cells (hBMSC-dSCs). These cells were seeded into synthetic conduits for bridging critical gaps in a rat model of sciatic nerve injury. With improvement in gait by 12-week post-bridging, evoked signals were also detectable across the bridged nerve. Confocal microscopy revealed axially aligned axons in association with MBP-positive myelin layers across the bridge in contrast to null in non-seeded controls. Myelinating hBMSC-dSCs within the conduit were positive for both MBP and human nucleus marker HuN. We then implanted hBMSC-dSCs into the contused thoracic cord of rats. By 12-week post-implantation, significant improvement in hindlimb motor function was detectable if chondroitinase ABC was co-delivered to the injured site; such cord segments showed axons myelinated by hBMSC-dSCs. Results support translation into a protocol by which lineage-committed hBMSC-dSCs become available for motor function recovery after traumatic injury to both peripheral and central nervous systems.

Neurological Survivorship Following Surgery for Degenerative Cervical Myelopathy: A Longitudinal Study on 195 Patients.

BACKGROUND: Long-term data on postoperative neurological survivorship for patients with degenerative cervical myelopathy (DCM) undergoing decompressive surgery are limited. The purposes of this study were to assess neurological survivorship after primary decompressive surgery for DCM and to identify predictors for postoperative deterioration. METHODS: A longitudinal clinical data set containing surgical details, medical comorbidities, and radiographic features was assembled for 195 patients who underwent a surgical procedure for DCM between 1999 and 2020, with a mean period of observation of 75.9 months. Kaplan-Meier curves were plotted, and a log-rank test was performed for the univariate analysis of factors related to neurological failure. Lasso regression facilitated the variable selection in the Cox proportional hazards model for multivariate analysis. RESULTS: The overall neurological survivorship was 89.3% at 5 years and 77.3% at 10 years. Cox multivariate analysis following lasso regression identified elevated hazard ratios (HRs) for suture laminoplasty (HR, 4.76; p < 0.001), renal failure (HR, 4.43; p = 0.013), T2 hyperintensity (HR, 3.34; p = 0.05), and ossification of the posterior longitudinal ligament (OPLL) (HR, 2.32; p = 0.032). Subgroup analysis among subjects with OPLL demonstrated that the neurological failure rate was significantly higher in the absence of fusion (77.8% compared with 26.3%; p = 0.019). CONCLUSIONS: Overall, patients who underwent a surgical procedure for DCM exhibited an extended period with neurological improvement. Cervical fusion was indicated in OPLL to reduce neurological failure. Our findings on predictors for early deterioration facilitate case selection, prognostication, and counseling as the volume of primary cervical spine surgeries and reoperations increases globally. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Post-Maturity Progression in Adolescent Idiopathic Scoliosis Curves of 40° to 50°.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) curves of 50° to 75° are inclined to progress and are thus indicated for surgery. Nevertheless, the natural history of curves of 40° to 50° following skeletal maturity remains uncertain and presents a clinical dilemma. The aim of this study was to determine the prevalence, rate, and prognostic indicators of curve progression within this patient group. METHODS: This was a retrospective study of 73 skeletally mature patients with AIS. Following yearly or more frequent follow-up, patients were stratified as having no progression (<5° increase) or progression (≥5° increase). Those with progression were further differentiated as having standard progression (<2° increase/year) or fast progression (≥2° increase/year). Radiographic parameters (coronal balance, sagittal balance, truncal shift, apical translation, T1 tilt, apical vertebral wedging) and height were determined on skeletal maturity. Parameters that were significantly associated with progression were subject to receiver operating characteristic (ROC) curve analysis. RESULTS: The average period of post-maturity follow-up was 11.8 years. The prevalence of progression was 61.6%. Among those with progression, the curve increased by a mean of 1.47° ± 1.22° per year, and among those with fast progression, by 3.0° ± 1.2° per year. Thoracic apical vertebral wedging (concave/convex vertebral height × 100) was more apparent in those with progression than in those without progression (84.1 ± 7.5 versus 88.6 ± 3.1; p = 0.003). Increased coronal imbalance (C7 plumb line to central sacral vertebral line) differentiated those with fast progression from others (16.0 ± 11.0 versus 8.7 ± 7.7 mm; p = 0.007). An ROC curve of height-corrected coronal balance demonstrated an area under the curve (AUC) of 0.722, sensitivity of 75.0%, and specificity of 72.5% in identifying fast progression. An ROC curve of height-corrected coronal balance together with apical vertebral wedging to identify those with progression demonstrated an AUC of 0.746, with specificity of 93.7% and sensitivity of 64.5%. CONCLUSIONS: While the majority of curves progressed, the average rate of progression was slow, and thus, yearly observation was a reasonable management approach. Upon validation in larger cohorts, apical wedging and coronal imbalance may identity patients suited for closer monitoring and early spinal fusion. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Length of Cervical Stenosis, Admission ASIA Motor Scores, and BASIC Scores Are Predictors of Recovery Rate Following Central Cord Syndrome.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: This study aims to determine whether quantitative magnetic resonance imaging (MRI) parameters and radiological scoring systems could be used as a reliable assessment tool for predicting neurological recovery trajectory following acute traumatic central cord injury syndrome (CCS). SUMMARY OF BACKGROUND DATA: Controversy remains in whether CCS should be managed conservatively or by early surgical decompression. It is essential to understand how clinical and radiological parameters correlate with neurological deficits and how they predict recovery trajectories. METHODS: We identified patients with CCS admitted between 2011 and 2018 with a minimum of 1-year follow-up. Cervical MRIs were analyzed for cord/canal dimensions, Brain and Spinal Injury Center (BASIC) scores and sagittal grading as ordinal scales of intraparenchymal cord injury. Japanese Orthopaedic Association (JOA) recovery rates (≥50% as good, < 50% as poor) were analyzed against these variables by logistic regression and receiver operator characteristic (ROC) curves. Additionally, we evaluated American Spinal Injury Association motor scale (AMS) scores/recovery rates. RESULTS: Sixty patients were included, of which 30 were managed conservatively and 30 via surgical decompression. The average follow-up duration for the entire cohort was (51.1 ±â€Š25.7) months. Upon admission, sagittal grading correlated with AMS and JOA scores (P < 0.01, ß = 0.48). Volume of the C2 to C7 canal and axial cord area over the site of maximal compression correlated with AMS and JOA scores respectively (P = 0.04, ß = 0.26; P = 0.01, ß = 0.28). We determined admission AMS more than 61 to be a clinical cutoff for good recovery (area under the receiver operating curve [AUC] = 0.74, 95% confidence interval [CI]: 0.61-0.85, sensitivity 80.9%, specificity 69.2%, P < 0.01). Radiological cutoffs to identify patients with poor recovery rates were length of cervical spinal stenosis more than 3.9 cm (AUC = 0.76, 95% CI: 0.63-0.87, specificity 91.7%, sensitivity 52.2%, P < 0.01), BASIC score of more than 1 (AUC = 0.69, 95% CI: 0.56-0.81, specificity 80.5%, sensitivity 51.1%, P = 0.02). Surgical decompression performed as a salvage procedure upon plateau of recovery did not improve neurological outcomes. CONCLUSION: Clinical and radiological parameters upon presentation were prognosticative of neurological recovery rates in CCS. Surgery performed beyond the acute post-injury period failed to improve outcomes.Level of Evidence: 3.

Application of deep learning upon spinal radiographs to predict progression in adolescent idiopathic scoliosis at first clinic visit.

BACKGROUND: Prediction of curve progression risk in adolescent idiopathic scoliosis (AIS) remains elusive. Prior studies have revealed the potential for three-dimensional (3D) morphological parameters to prognosticate progression, but these require specialized biplanar imaging equipment and labor-intensive software reconstruction. This study aimed to formulate a deep learning model with standing posteroanterior (PA) X-rays at first clinic visit to differentiate between progressive (P) and non-progressive (NP) curves. METHODS: For this retrospective cohort study, we identified patients presenting with AIS between October 2015 to April 2020 at our tertiary referral centre. Patients with mild curvatures (11 - 30o) who were skeletally immature (Risser sign of ≤2) were recruited. Patients receiving biplanar X-ray radiographs (EOS™) were divided between a training-cross-validation cohort (328 patients) and independent testing cohort (110 patients). Another 52 patients receiving standard PA spinal X-rays were recruited for cross-platform validation. Following 3D reconstruction, we designated the major curve apex upon PA X-rays as the region of interest (ROI) for machine learning. A self-attentive capsule network was constructed to differentiate between curves manifesting P and NP trajectories. A two-stage transfer learning strategy was introduced to pre-train and fine-tune the model. Model performance (accuracy, sensitivity, specificity) was compared to that of traditional convolutional neural networks (CNNs) and a clinical parameter-based logistic regression model. FINDINGS: 3D reconstruction identified that apical rotation of the major curve and torsion were significantly different between P and NP curve trajectories. Our predictive model utilizing an ROI centered on the major curve apex achieved an accuracy of 76.6%, a sensitivity of 75.2% and a specificity of 80.2% upon independent testing. Cross-platform performance upon standard standing PA X-rays yielded an accuracy of 77.1%, a sensitivity of 73.5% and a specificity of 81.0%. Errors in prediction occurred when the degree of apical rotation / torsion was discrepant from that of the subsequent curve trajectory but could be rectified by considering serial X-rays. Performance was superior to that of traditional CNNs as well as clinical parameter-based regression models. INTERPRETATION: This is the first report of automated prediction of AIS curve progression based on radiomics and deep learning, towards directing treatment strategy at first visit. Patients predicted to be at-risk of progression may be counselled to receive early bracing with enforcement of treatment compliance. Over-treatment may be avoided in curves deemed to be non-progressive. Results need to be consolidated in larger sample populations of different ethnicities. FUNDING: The Society for the Relief of Disabled Children (SRDC).

Prospects of cell replacement therapy for the treatment of degenerative cervical myelopathy.

Degenerative cervical myelopathy (DCM) presents insidiously during middle-age with deterioration in neurological function. It accounts for the most common cause of non-traumatic spinal cord injury in developed countries and disease prevalence is expected to rise with the aging population. Whilst surgery can prevent further deterioration, biological therapies may be required to restore neurological function in advanced disease. Cell replacement therapy has been inordinately focused on treatment of traumatic spinal cord injury yet holds immense promise in DCM. We build upon this thesis by reviewing the pathophysiology of DCM as revealed by cadaveric and molecular studies. Loss of oligodendrocytes and neurons occurs via apoptosis. The tissue microenvironment in DCM prior to end-stage disease is distinct from that following acute trauma, and in many ways more favourable to receiving exogenous cells. We highlight clinical considerations for cell replacement in DCM such as selection of cell type, timing and method of delivery, as well as biological treatment adjuncts. Critically, disease models often fail to mimic features of human pathology. We discuss directions for translational research towards clinical application.

Juxtacrine signalling via Notch and ErbB receptors in the switch to fate commitment of bone marrow-derived Schwann cells.

The phenotypic instability of adult tissue-derived Schwann cell-like cells (SCLCs) as revealed upon withdrawal of glia-inducing culture supplements limits their clinical utility for cell therapy and disease modelling. We previously overcame this limitation by co-culturing bone marrow-derived SCLCs with neurons purified from developing rat and subsequently human sensory neurons such that direct contact between cell types accomplished the cell-intrinsic switch to the Schwann cell fate. Here, our search for juxtacrine instructive signals found both Notch ligands and neuregulin-1 type III localized on the surface of DRG neurons via live cell immunocytochemistry. Bypassing ligand-induced release of the Notch intracellular domain (NICD) by transient transfection of SCLCs with the pAdlox/V5-His-NICD construct was shown to upregulate ErbB2/3. Interaction of ErbB2/3 with neuregulin-1 type III (NRG1 type III) as presented on neurons then mediated the switch to the Schwann cell fate as demonstrated by expression of S100ß/p75/ Sox10/Krox20. In contrast, treatment of cocultures with γ-secretase inhibitor perturbed Notch signalling in SCLCs and consequently deterred both upregulation of ErbB2/3 and the transition to the Schwann cell fate. Taken together, juxtacrine signalling via Notch is key to the upregulation of ErbB receptors for neuregulin-driven commitment of SCLCs to the Schwann cell fate.

A review of the manufacturing process and infection rate of 3D-printed models and guides sterilized by hydrogen peroxide plasma and utilized intra-operatively.

3D printing in the context of medical application can allow for visualization of patient-specific anatomy to facilitate surgical planning and execution. Intra-operative usage of models and guides allows for real time feedback but ensuring sterility is essential to prevent infection. The additive manufacturing process restricts options for sterilisation owing to temperature sensitivity of thermoplastics utilised for fabrication. Here, we review one of the largest single cohorts of 3D models and guides constructed from Acrylonitrile butadiene styrene (ABS) and utilized intra-operatively, following terminal sterilization with hydrogen peroxide plasma. We describe our work flow from initial software rendering to printing, sterilization, and on-table application with the objective of demonstrating that our process is safe and can be implemented elsewhere. Overall, 7% (8/114 patients) of patients developed a surgical site infection, which was not elevated in comparison to related studies utilizing traditional surgical methods. Prolonged operation time with an associated increase in surgical complexity was identified to be a risk factor for infection. Low temperature plasma-based sterilization depends upon sufficient permeation and contact with surfaces which are a particular challenge when our 3D-printouts contain diffusion-restricted luminal spaces as well as hollows. Application of printouts as guides for power tools may further expose these regions to sterile bodily tissues and result in generation of debris. With each printout being a bespoke medical device, it is important that the multidisciplinary team involved in production and application understand potential pitfalls to ensuring sterility as to minimize infection risk.

Transfer of the anterior gluteus maximus to address abductor deficiency following soft tissue tumour excision.

Hip abductor deficiency is most commonly encountered in the context of degeneration of the hip, and techniques for reconstruction pioneered by arthroplasty surgeons. We adopted a local muscle transfer technique utilizing the anterior half of the gluteus maximus for abductor reconstruction following soft tissue tumour excision in a young female patient. The patient of concern had a solitary fibrous tumour located between the right gluteus medius and minimus detected as an incidental finding. Marginal excision of the mass resulted in removal of the gluteus medius. The anterior half of the gluteus maximus was transferred and attached to the decorticated lateral greater trochanter by means of suture anchors and transosseous sutures. The patient initially demonstrated a Trendelenburg gait and limited abduction against gravity. By 1-year post-operation, there was return of normal gait and recovery of hip abductor power. This is the first report of anterior gluteus maximus transfer being successfully applied for soft tissue reconstruction around the hip subsequent to tumour excision.

Comparing 3 Different Techniques of Patella Fracture Fixation and Their Complications.

INTRODUCTION: Patella fractures managed by fixation with metal implants often cause local soft tissue irritation and necessitate implant removal. An alternative is to utilize suture-based fixation methods. We have adopted suture and hybrid fixation in the routine management of patella fractures. Here, we compare the results of 3 fixation techniques. MATERIALS AND METHODS: Eighty-seven eligible patients underwent patella fracture fixation over a 3-year period. As determined by fracture configuration, patients received (1) suture fixation (transosseous sutures and figure-of-eight tension banding with FiberWire), (2) hybrid fixation (transosseous FiberWire sutures and metal tension banding), or (3) metal fixation. Primary outcome measures included reoperation rate and soft tissue irritation. Secondary outcomes included surgical complications, radiological, and functional parameters. RESULTS: Reoperation rate was highest for metal fixation (25/57, 43.9%) and lowest for suture fixation (2/13, 15.4%). Soft tissue irritation necessitating implant removal was the predominant reason for reoperation and was significantly less prevalent following suture fixation (1/13, 7.7%, P < .01). Hybrid fixation resulted in similar rates of soft tissue irritation (6/17, 35.3%) and implant removal (7/17, 41.2%) as compared to metal fixation. There was a significant increase in patella baja (13/17, 76.5%) and reduction in Insall-Salvati ratio (0.742; 95% confidence interval: 0.682-0.802) following hybrid fixation as compared to the other 2 fixation methods (P < .05). DISCUSSION: Suture fixation results in the least amount of soft tissue irritation and lowest reoperation rate, but these advantages are negated with the addition of a metal tension band wire. Hybrid fixation also unbalances the extensor mechanism. CONCLUSION: Patients should be counseled as to the expected sequelae of their fixation method. Suture fixation is the favored means to fix distal pole fractures of the patella. An additional metal tension band loop may confer additional stability but should be applied with caution.