Single-Molecule Maps of Membrane Insertion by Amyloid-ß Oligomers Predict Their Toxicity.

The interaction of small Amyloid-ß (Aß) oligomers with the lipid membrane is an important component of the pathomechanism of Alzheimer's disease (AD). However, oligomers are heterogeneous in size. How each type of oligomer incorporates into the membrane, and how that relates to their toxicity, is unknown. Here, we employ a single molecule technique called Q-SLIP (Quencher-induced Step Length Increase in Photobleaching) to measure the membrane insertion of each monomeric unit of individual oligomers of Aß42, Aß40, and Aß40-F19-Cyclohexyl alanine (Aß40-F19Cha), and correlate it with their toxicity. We observe that the N-terminus of Aß42 inserts close to the center of the bilayer, the less toxic Aß40 inserts to a shallower depth, and the least toxic Aß40-F19Cha has no specific distribution. This oligomer-specific map provides a mechanistic representation of membrane-mediated Aß toxicity and should be a valuable tool for AD research.

Do Tofacitinib Generics Exhibit Conventional Synthetic Disease-Modifying Anti-rheumatic Drug and Non-steroidal Anti-inflammatory Drug-Sparing Ability in the Management of Axial Spondyloarthritis?

INTRODUCTION: Tofacitinib has emerged as a therapeutic option for axial spondyloarthritis (axSpA) following successful clinical trials. The evidence on the efficacy of tofacitinib generics in the management of axSpA is limited. In India, the usage of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) is commonplace in the management of axSpA. Our primary aim was to identify the csDMARD and non-steroidal anti-inflammatory drug (NSAID)-sparing role of tofacitinib generics in an axSpA population. METHODS: This was a retrospective study in a real-world clinical setting. Data from nine rheumatology centers across India were analyzed for 168 patients with active axSpA who were initiated on generic tofacitinib 5 mg twice daily in conjunction with csDMARDs and NSAIDs, over a duration of six months. Our primary outcome was to evaluate the csDMARD and NSAID-sparing effect of tofacitinib generics, while the secondary outcome assessed safety profiles and efficacy at six months. RESULTS: The median Ankylosing Spondylitis Disease Activity Score (ASDAS) erythrocyte sedimentation rate (ESR) score of the study population was 3.91 (3.26, 4.56). Alongside tofacitinib generics, 121 (72%) patients were co-administered csDMARDs (methotrexate/sulfasalazine/both), and 90 (53.6%) patients were co-administered NSAIDs. The csDMARD, NSAID, and combined csDMARD + NSAID-sparing effects of tofacitinib generics were seen in 85 (50.6%), 156 (92.9%), and 81 (48.2%) patients, respectively. Adverse events were mild and well-tolerated. At six months, 124 (57.9%) patients had attained clinically important improvement in ASDAS ESR score, and the median decrease in ASDAS ESR score was 2.02 (1.18, 2.96). CONCLUSION: This real-world study provides evidence supporting the csDMARD and NSAID-sparing ability of tofacitinib generics in the treatment of axSpA. Tofacitinib generics displayed a good safety profile and showed signals of efficacy as well.

Deterministic early endosomal maturations emerge from a stochastic trigger-and-convert mechanism.

Endosomal maturation is critical for robust and timely cargo transport to specific cellular compartments. The most prominent model of early endosomal maturation involves a phosphoinositide-driven gain or loss of specific proteins on individual endosomes, emphasising an autonomous and stochastic description. However, limitations in fast, volumetric imaging long hindered direct whole cell-level measurements of absolute numbers of maturation events. Here, we use lattice light-sheet imaging and bespoke automated analysis to track individual very early (APPL1-positive) and early (EEA1-positive) endosomes over the entire population, demonstrating that direct inter-endosomal contact drives maturation between these populations. Using fluorescence lifetime, we show that this endosomal interaction is underpinned by asymmetric binding of EEA1 to very early and early endosomes through its N- and C-termini, respectively. In combination with agent-based simulation which supports a 'trigger-and-convert' model, our findings indicate that APPL1- to EEA1-positive maturation is driven not by autonomous events but by heterotypic EEA1-mediated interactions, providing a mechanism for temporal and population-level control of maturation.

Occurrence and outcome of COVID-19 in AIRD patients on concomitant treatment with Tofacitinib- results from KRA COVID COHORT (KRACC) subset.

INTRODUCTION: We assessed the risk factors and outcome of COVID-19 in patients with autoimmune rheumatic diseases(AIRD) who contracted infection while on background treatment with tofacitinib. METHODS: This is a non-interventional, cross-sectional, questionnaire based telephonic study which included consecutive AIRD patients on tofacitinib co-treatment. Data related to the AIRD subset, disease modifying anti rheumatic drugs(DMARDs) including glucocorticoids and comorbidities, was collected from 7 rheumatology centers across Karnataka during the second wave of COVID-19 pandemic. The information about COVID-19 occurrence and COVID-19 vaccination was recorded. RESULTS: During the study period (Jun-July 2021), 335 AIRD patients (80.6% female) on treatment with tofacitinib were included. The mean duration of tofacitinib use was 3.4+/-3.1months. Thirty-six(10.75%) patients developed COVID-19. Diabetes mellitus (p = 0.04 (OR 2.60 (1.13-5.99)) was identified as a risk factor for COVID-19 in our cohort. Almost half of our cohort was COVID-19 vaccinated with at least one dose, with resultant decline in incidence of COVID-19(OR 0.15 (0.06-0.39) among the vaccinated. Recovery amongst COVID-19 infection group was 91.2%. CONCLUSIONS: The subset of AIRD patients who were on treatment with tofacitinib were found to have a higher rate of COVID-19 infection as compared to our KRACC cohort. Pre-existing comorbidity of diabetes mellitus was the significant risk factor in our cohort. This subset of the KRACC cohort shows RA patients had a lesser infection and PsA patients had a higher infection.

Post processing of low cost Aligners fabricated by additive manufacturing process to enhance the surface quality and functionality.

Additive Manufacturing (AM) processes have ample advantages compared to traditional manufacturing processes, including mass customization, material efficiency, bioprinting, and fabrication of complex geometries with reduced lead time. Despite such benefits, it suffers most from staircase effects that deteriorate the fabricated part's surface quality. Nowadays, additively manufactured aligners are suitable for treating malocclusion and temporomandibular defects of teeth. Fused Deposition Modelling (FDM) is one of the best substitutes for clear aligners production to reduce per-unit cost. Glycol-modified Polyethylene Terephthalate (PETG) is opted as the material to fabricate the clear aligners due to its biocompatibility and non-toxicity. However, the poor surface quality of the additively manufactured is a major challenge in developing clear aligners with the FDM. A novel experimental setup is designed and developed to enable Chemical Vapor Smoothing (CVS) to enhance the surface quality of the clear aligners. Furthermore, based on the Surface roughness, the comparison is made between the surface quality polished with various chemicals (namely methylethylketone (also known as 2-butanone), toluene and, cyclohexanone). Moreover, Response Surface Methodology (RSM) is used to analyze the impact of different process parameters (i.e., the chemical volume, exposure time, and workpiece orientation) on the surface quality of the clear aligners. Moreover, RSM shows that the impact of the clear aligners orientation on %ΔRa during the CVS is higher than other process parameters. Results demonstrate that cyclohexanone produces more uniform surface quality with a 92.73% reduction in surface roughness compared to methylethylketone and toluene on PETG, i.e., 89.66% and 88.63%, respectively. The developed surface finishing method is capable of producing uniform, smooth surfaces over the FDM-fabricated PETG clear aligners.

Risk factors associated with COVID-19 in systemic lupus erythematosus: Results from a longitudinal prospective cohort.

INTRODUCTION: Patients with SLE (systemic lupus erythematosus) have a higher risk of infection due to dysregulated immune system as well as long-term use of immunosuppressants (IS). This could influence the risk of COVID-19 and its outcome. METHODS: We conducted a longitudinal prospective study across 15 rheumatology centres during the first wave of the pandemic to understand the risk factors contributing to COVID-19 in SLE patients. During the 6 months follow-up, those who tested positive for COVID-19, their clinical course and outcome information were recorded. RESULTS: Through the study period (April-December 2020), 36/1379 lupus patients (2.9%) developed COVID-19. On analysing the COVID-19 positive versus negative cohort during the study period, male gender (adjusted RR 3.72, 95% C.I. 1.85,7.51) and diabetes (adjusted RR 2.94, 95% C.I. 1.28, 6.79) emerged as the strongest risk factors for COVID-19, in the adjusted analysis. There was no significant influence of organ involvement, hydroxychloroquine, glucocorticoid dosage (prednisolone< 7.5 mg or ≥ 7.5 mg/day) or IS on the risk of COVID-19. There was only one death (1/36) among the lupus patients due to COVID-19. CONCLUSION: Traditional risk factors rather than lupus disease process or IS influenced the risk of COVID-19 in our cohort.

Review of EEG-based neurofeedback as a therapeutic intervention to treat depression.

Depression, or major depressive disorder, is a common mental disorder that affects individuals' behavior, mood, and physical health, and its prevalence has increased during the lockdowns implemented to curb the COVID-19 pandemic. There is an urgent need to update the treatment recommendations for mental disorders during such crises. Conventional interventions to treat depression include long-term pharmacotherapy and cognitive behavioral therapy. Electroencephalogram-neurofeedback (EEG-NF) training has been suggested as a non-invasive option to treat depression with minimal side effects. In this systematic review, we summarize the recent literature on EEG-NF training for treating depression. The 12 studies included in our final sample reported that despite several issues related to EEG-NF practices, patients with depression showed significant cognitive, clinical, and neural improvements following EEG-NF training. Given its low cost and the low risk of side effects due to its non-invasive nature, we suggest that EEG-NF is worth exploring as an augmented tool for patients who already receive standard medications but remain symptomatic, and that EEG-NF training may be an effective intervention tool that can be utilized as a supplementary treatment for depression. We conclude by providing some suggestions related to experimental designs and standards to improve current EEG-NF training practices for treating depression.

Neurofeedback for the Education of Children with ADHD and Specific Learning Disorders: A Review.

Neurofeedback (NF) is a type of biofeedback in which an individual's brain activity is measured and presented to them to support self-regulation of ongoing brain oscillations and achieve specific behavioral and neurophysiological outcomes. NF training induces changes in neurophysiological circuits that are associated with behavioral changes. Recent evidence suggests that the NF technique can be used to train electrical brain activity and facilitate learning among children with learning disorders. Toward this aim, this review first presents a generalized model for NF systems, and then studies involving NF training for children with disorders such as dyslexia, attention-deficit/hyperactivity disorder (ADHD), and other specific learning disorders such as dyscalculia and dysgraphia are reviewed. The discussion elaborates on the potential for translational applications of NF in educational and learning settings with details. This review also addresses some issues concerning the role of NF in education, and it concludes with some solutions and future directions. In order to provide the best learning environment for children with ADHD and other learning disorders, it is critical to better understand the role of NF in educational settings. The review provides the potential challenges of the current systems to aid in highlighting the issues undermining the efficacy of current systems and identifying solutions to address them. The review focuses on the use of NF technology in education for the development of adaptive teaching methods and the best learning environment for children with learning disabilities.

An Algorithm for Task Allocation and Planning for a Heterogeneous Multi-Robot System to Minimize the Last Task Completion Time.

This paper proposes an algorithm that provides operational strategies for multiple heterogeneous mobile robot systems utilized in many real-world applications, such as deliveries, surveillance, search and rescue, monitoring, and transportation. Specifically, the authors focus on developing an algorithm that solves a min-max multiple depot heterogeneous asymmetric traveling salesperson problem (MDHATSP). The algorithm is designed based on a primal-dual technique to operate given multiple heterogeneous robots located at distinctive depots by finding a tour for each robot such that all the given targets are visited by at least one robot while minimizing the last task completion time. Building on existing work, the newly developed algorithm can solve more generalized problems, including asymmetric cost problems with a min-max objective. Though producing optimal solutions requires high computational loads, the authors aim to find reasonable sub-optimal solutions within a short computation time. The algorithm was repeatedly tested in a simulation with varying problem sizes to verify its effectiveness. The computational results show that the algorithm can produce reliable solutions to apply in real-time operations within a reasonable time.

A prospective longitudinal study evaluating the influence of immunosuppressives and other factors on COVID-19 in autoimmune rheumatic diseases.

BACKGROUND: We conducted this study to identify the influence of prolonged use of hydroxychloroquine (HCQ), glucocorticoids and other immunosuppressants (IS) on occurrence and outcome of COVID-19 in patients with autoimmune rheumatic diseases (AIRDs). METHODS: This was a prospective, multicenter, non-interventional longitudinal study across 15 specialist rheumatology centers. Consecutive AIRD patients on treatment with immunosuppressants were recruited and followed up longitudinally to assess parameters contributing to development of COVID-19 and its outcome. RESULTS: COVID-19 occurred in 314 (3.45%) of 9212 AIRD patients during a median follow up of 177 (IQR 129, 219) days. Long term HCQ use had no major impact on the occurrence or the outcome of COVID-19. Glucocorticoids in moderate dose (7.5-20 mg/day) conferred higher risk (RR = 1.72) of infection. Among the IS, Mycophenolate mofetil (MMF), Cyclophosphamide (CYC) and Rituximab (RTX) use was higher in patients with COVID 19. However, the conventional risk factors such as male sex (RR = 1.51), coexistent diabetes mellitus (RR = 1.64), pre-existing lung disease (RR = 2.01) and smoking (RR = 3.32) were the major contributing risk factors for COVID-19. Thirteen patients (4.14%) died, the strongest risk factor being pre-existing lung disease (RR = 6.36, p = 0.01). Incidence (17.5 vs 5.3 per 1 lakh (Karnataka) and 25.3 vs 7.9 per 1 lakh (Kerala)) and case fatality (4.1% vs 1.3% (Karnataka) and 4.3% vs 0.4% (Kerala)) rate of COVID-19 was significantly higher (p < 0.001) compared to the general population of the corresponding geographic region. CONCLUSIONS: Immunosuppressants have a differential impact on the risk of COVID-19 occurrence in AIRD patients. Older age, males, smokers, hypertensive, diabetic and underlying lung disease contributed to higher risk. The incidence rate and the case fatality rate in AIRD patients is much higher than that in the general population.

Matched-Pair Analysis of Magnetic Resonance Images for Location of the Common Peroneal Nerve in Valgus Knees: Comparison with the Varus Knees.

This study aimed to assess the distance and angular location of the common peroneal nerve (CPN) on axial magnetic resonance imaging (MRI) in the valgus knees and compare the measurements with those obtained from the control group. We compared the location of the CPN according to the type of alignment by performing a subgroup analysis. From January 2009 to December 2019, we identified 41 knees with preoperative MRI in patients who underwent total knee arthroplasty (TKA) for valgus deformity (valgus group). We performed one-to-two matched-pair analysis to a cohort of patients who underwent MRI but were not candidates for TKA (control group), according to sex and age. The valgus group was classified according to the grading system reported by Ranawat et al, and the control group was also subdivided according to the hip-knee-ankle (HKA) angle obtained from lower extremity scanography: neutral (-3 to +3 degrees from the neutral mechanical axis), valgus (> +3 degrees), and varus alignment (< -3 degrees). Distance between the CPN and posterolateral cortex of the tibia at the knee joint (distance J) and tibial cut level (distance C) were measured. Angle of the CPN from the central anteroposterior axis of the tibia (angle α) was measured. We compared the measurements between the groups. Distance J was significantly closer in the valgus group (p < 0.001), whereas angle α was significantly smaller in the valgus group (p < 0.001). However, no significant differences were found in the subgroup analysis. Moreover, a significant correlation was found between distance J and the HKA angle (p < 0.001). The location of the CPN in the valgus knees was closer to the posterolateral cortex of the tibia at the joint level and showed a smaller angle than that in the other aligned knees. We recommend that lateral soft tissue release for valgus knees should not be performed at the joint line. The results of this study suggest that this would be less safe than a release performed at the level of the proximal tibial bone resection.

Age-related and individual variations in altered prefrontal and cerebellar connectivity associated with the tendency of developing internet addiction.

Internet addiction refers to problematic patterns of internet use that continually alter the neural organization and brain networks that control impulsive behaviors and inhibitory functions. Individuals with elevated tendencies to develop internet addiction represent the transition between healthy and clinical conditions and may progress to behavioral addictive disorders. In this network neuroscience study, we used resting-state functional magnetic resonance imaging (rs-fMRI) to examine how and whether individual variations in the tendency of developing internet addiction rewire functional connectivity and diminish the amplitude of spontaneous low-frequency fluctuations in healthy brains. The influence of neurocognitive aging (aged over 60 years) on executive-cerebellar networks responsible for internet addictive behavior was also investigated. Our results revealed that individuals with an elevated tendency of developing internet addiction had disrupted executive-cerebellar networks but increased occipital-putamen connectivity, probably resulting from addiction-sensitive cognitive control processes and bottom-up sensory plasticity. Neurocognitive aging alleviated the effects of reduced mechanisms of prefrontal and cerebellar connectivity, suggesting age-related modulation of addiction-associated brain networks in response to compulsive internet use. Our findings highlight age-related and individual differences in altered functional connectivity and the brain networks of individuals at a high risk of developing internet addictive disorders. These results offer novel network-based preclinical markers of internet addictive behaviors for individuals of different ages.

Healthy Aging Alters the Functional Connectivity of Creative Cognition in the Default Mode Network and Cerebellar Network.

Creativity is a higher-order neurocognitive process that produces unusual and unique thoughts. Behavioral and neuroimaging studies of younger adults have revealed that creative performance is the product of dynamic and spontaneous processes involving multiple cognitive functions and interactions between large-scale brain networks, including the default mode network (DMN), fronto-parietal executive control network (ECN), and salience network (SN). In this resting-state functional magnetic resonance imaging (rs-fMRI) study, group independent component analysis (group-ICA) and resting state functional connectivity (RSFC) measures were applied to examine whether and how various functional connected networks of the creative brain, particularly the default-executive and cerebro-cerebellar networks, are altered with advancing age. The group-ICA approach identified 11 major brain networks across age groups that reflected age-invariant resting-state networks. Compared with older adults, younger adults exhibited more specific and widespread dorsal network and sensorimotor network connectivity within and between the DMN, fronto-parietal ECN, and visual, auditory, and cerebellar networks associated with creativity. This outcome suggests age-specific changes in the functional connected network, particularly in the default-executive and cerebro-cerebellar networks. Our connectivity data further elucidate the critical roles of the cerebellum and cerebro-cerebellar connectivity in creativity in older adults. Furthermore, our findings provide evidence supporting the default-executive coupling hypothesis of aging and novel insights into the interactions of cerebro-cerebellar networks with creative cognition in older adults, which suggest alterations in the cognitive processes of the creative aging brain.

Static and dynamic functional connectivity supports the configuration of brain networks associated with creative cognition.

Creative cognition is recognized to involve the integration of multiple spontaneous cognitive processes and is manifested as complex networks within and between the distributed brain regions. We propose that the processing of creative cognition involves the static and dynamic re-configuration of brain networks associated with complex cognitive processes. We applied the sliding-window approach followed by a community detection algorithm and novel measures of network flexibility on the blood-oxygen level dependent (BOLD) signal of 8 major functional brain networks to reveal static and dynamic alterations in the network reconfiguration during creative cognition using functional magnetic resonance imaging (fMRI). Our results demonstrate the temporal connectivity of the dynamic large-scale creative networks between default mode network (DMN), salience network, and cerebellar network during creative cognition, and advance our understanding of the network neuroscience of creative cognition.

Screening for Hydroxychloroquine Retinal Toxicity in Indian Patients.

OBJECTIVE: Several studies have reported hydroxychloroquine (HCQ) retinal toxicity in East Asian patients. However, at present, there are limited data from Indian patients. The aim of this study was to investigate the prevalence and pattern of HCQ retinal toxicity in Indian population and to see if screening protocol for retinal toxicity in Indian patients should be any different to others. METHODS: This was a cross-sectional study involving adult patients with autoimmune rheumatic diseases who had received HCQ for at least 5 years or a cumulative dose of at least 500 g. Retinal toxicity was evaluated using fundus examination, visual fields 10-2 and 30-2 protocol, and spectral domain optical coherence tomography. RESULTS: Of 110 patients screened, retinal toxicity was found in 7 patients (6.36%). A parafoveal pattern was found in 4 patients, whereas a mixed parafoveal and perifoveal pattern was found in 3 patients. None of the patients had isolated perifoveal pattern. Except for the one patient, all the patients with retinal toxicity had more than 10 years (mean, 13 ± 4.89 years; range, 5-20 years) of HCQ usage with a mean cumulative dose of 1573.7 ± 771.5 g. The mean daily dose was 5 ± 1.6 mg/kg per day. CONCLUSIONS: Hydroxychloroquine retinal toxicity is more common than previously recognized in patients who have used the drug for more than 5 years. The toxicity manifests as a parafoveal or a mixed parafoveal and perifoveal pattern in Indian patients.

Anti-drug antibodies and low serum trough infliximab levels correlate with disease activity measures in spondyloarthritis patients on an as-needed infliximab treatment.

AIM: In India, many centers use infliximab at lower doses of 3-5 mg/kg without the loading dose for spondyloarthritis (SpA) patients. It is then continued on an as-required basis, rather than a fixed schedule. Our study was undertaken to see if the trough drug levels and anti-drug antibodies in patients with SpA treated with as-needed infliximab dosing correlated with the disease activity measures. METHODS: Thirty-five adult SpA patients in the age group 18-70 years were recruited. They had received three or more infusions of infliximab at 3-5 mg/kg over the past 6 to 12 months. Patient's serum tumor necrosis factor-α, trough infliximab levels and anti-drug antibodies were measured by enzyme-linked immunosorbent assay technique. The disease activity was quantified by Ankylosing Spondylitis Disease Activity Score - erythrocyte sedimentation rate/ C-reactive protein (ASDAS-ESR/CRP) scores. Correlation between quantitative variables was analyzed by the Spearman's correlation assay. The difference in mean trough infliximab and ASDAS between the drug antibody positive and negative patients was assessed using the Mann-Whitney U test. RESULTS: There was a significant negative correlation between the trough infliximab levels and the ASDAS-ESR (rs = -0.57, P < 0.01) and ASDAS-CRP scores (rs = -0.53, P < 0.01). Anti-drug antibodies were positive in 68.7% of the patients and in comparison to the antibody negative patients, had significantly higher ASDAS-ESR and ASDAS-CRP scores. CONCLUSIONS: Spondyloarthritis patients on low-dose, as-needed infliximab therapy, have both the trough infliximab and anti-drug antibodies correlate significantly with the measures of disease activity. We hypothesize that trough infliximab levels and anti-drug antibodies may be used to predict a suboptimal response due to secondary resistance in SpA patients.

KinVis: a visualization tool to detect cryptic relatedness in genetic datasets.

MOTIVATION: It is important to characterize individual relatedness in terms of familial relationships and underlying population structure in genome-wide association studies for correct downstream analysis. The characterization of individual relatedness becomes vital if the cohort is to be used as reference panel in other studies for association tests and for identifying ethnic diversities. In this paper, we propose a kinship visualization tool to detect cryptic relatedness between subjects. We utilize multi-dimensional scaling, bar charts, heat maps and node-link visualizations to enable analysis of relatedness information. AVAILABILITY AND IMPLEMENTATION: Available online as well as can be downloaded at http://shiny-vis.qcri.org/public/kinvis/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Comparison of quadriceps snip and tibial tubercle osteotomy in revision for infected total knee arthroplasty.

PURPOSE: Controversies exist regarding the ideal approach in a revision total knee arthroplasty for infection, providing adequate exposure with minimum complications. The purpose of this study was to compare the results of second stage revision total knee arthroplasty (TKA) between tibial tubercle osteotomy (TTO) and quadriceps snip (QS) approaches for infected TKA. METHODS: The clinical and radiological outcomes of 27 patients of TTO and 21 patients of QS in second stage revision TKA for infected TKA were compared with an average follow up of 51 months. We evaluated the clinical outcomes including HSS score, WOMAC score, flexion contracture, and maximal flexion between two groups. The radiological outcomes in terms of femorotibial alignment, patellar height and complications were also compared. RESULTS: At the final follow-up, KSS score, HSS score, WOMAC score, flexion contracture, and maximal flexion showed no statistically significant differences between the two groups. The femorotibial alignment and patellar height also showed no differences between the two groups. During the surgery, patellar tendon partial avulsion was more commonly observed in the QS group than in the TTO group (five vs two cases). CONCLUSION: Both tibial tubercle osteotomy and quadriceps snip in revision TKA were considered as good approaches without significant complications. However, cautious exposure of patellar tendon or strong fixation of the osteotomy is needed to minimize the complications.

Accuracy and safety of free-hand pedicle screw fixation in age less than 10 years.

BACKGROUND: Pedicle screws are being used commonly in the treatment of various spinal disorders. However, use of pedicle screws in the pediatric population is not routinely recommended because of the risk of complications. The present study was to evaluate the safety of pedicle screws placed in children aged less than 10 years with spinal deformities and to determine the accuracy and complication (early and late) of pedicle screw placement using the postoperative computed tomography (CT) scans. MATERIALS AND METHODS: Thirty one patients (11 males and 20 females) who underwent 261 pedicle screw fixations (177 in thoracic vertebrae and 84 in lumbar vertebrae) for a variety of pediatric spinal deformities at a single institution were included in the study. The average age of patients was 7 years and 10 months. These patients underwent postoperative CT scan which was assessed by two independent observers (spine surgeons) not involved in the treatment. RESULTS: Breach rate was 5.4% (14/261 screws) for all pedicles. Of the 177 screws placed in the thoracic spine, 13 (7.3%) had breached the pedicle, that is 92.7% of the screws were accurately placed within pedicles. Seven screws (4%) had breached the medial pedicle wall, 4 screws (2.3%) had breached the lateral pedicle wall and 2 screws (1.1%) had breached the superior or inferior pedicle wall respectively. Of the 84 screws placed in the lumbar spine, 83 (98.8%) screws were accurately placed within the pedicle. Only 1 screw (1.2%) was found to be laterally displaced. In addition, the breach rate was found to be 4.2% (11/261 screws) with respect to the vertebral bodies. No neurological, vascular or visceral complications were encountered. CONCLUSIONS: The accuracy of pedicle screw placement in pedicles and vertebral bodies were 94.6% and 95.8% respectively and there was no complication related to screw placement noted until the last followup. These results suggest that free-hand pedicle screw fixation can be safely used in patients younger than 10 years to treat a variety of spinal disorders.