BERTOLOTTI SYNDROME: AN UNDER RECOGNIZED CAUSE OF INFLAMMATORY BACK PAIN?

BackgroundBertolotti syndrome describes a lumbosacral transitional vertebra (LSTV) which causes symptoms, usually low back pain. LATV is a congenital anomaly where the L5 vertebra has an unusual morphology. Bertolotti syndrome is an under-recognised condition by clinicians.ObjectivesTo clarify the presentation of Bertolotti syndrome, whether there are features of inflammatory back pain (IBP) and the effect on quality of life.MethodsIn this pilot study, 62 patients with LSTV were identified on imaging (plain x-ray). Imaging was performed for a variety of indications, predominently for back pain. In total, 34 patients agreed to take part, with 18 returning questionnaires. Questionnaires were selected for face vailidity and included: Calin IBP Questionnaire, EQ-5D Questionnaire, Visual analogue pain scale (VAS-P). In view of Covid restrictions all contact was by phone and questionnaires were completed online or returned via post.Plain X-rays visualising the lumbar spine were assessed for radiological features of LSTV.ResultsSeventeen (94%) of the participants (n=18) recorded a VAS-P score >3, indicating a clinically significant level of pain. The mean VAS-P score was 6 (range of 2-9). 89% of respondents scored at least 3/5 in the Calin questionnaire. Of the 5 features of inflammatory back pain in the Calin questionnaire, 4 out of the 5 were reported by most respondents. The exception was ‘improvement on exercise', which was only reported by 18% of respondents. Quality of life was impaired-EQ-5D (mean: 0.503, range -0.074 to 0.796).The commonest radiological abnormality was enlarged transverse process (100%) followed by pseudoarticulation with the sacrum (83%) and scoliosis (33%). Presence of sclerosis and/or osteoarthritis at the pseudoarticulation was associated with worse pain scores. Female respondents reported worse pain.ConclusionThese results suggest Bertolotti syndrome is associated with pain in the majority of patients and affects quality of life,. The character and site of the pain suggests that Bertollotti syndrome should be considered in the differential diagnosis of spondyloarthritis.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsSimon Stebbings Consultant of: Abbvie.Janssen, Ciara White: None declared, Terence Doyle: None declared.

Deep learning-based COVID-19 triage tool: An observational study on an X-ray dataset

Background: Easy availability, low cost, and low radiation exposure make chest radiography an ideal modality for coronavirus disease 2019 (COVID-19) detection. Objective(s): In this study, we propose the use of an artificial intelligence (AI) algorithm to automatically detect abnormalities associated with COVID-19 on chest radiographs. We aimed to evaluate the performance of the algorithm against the interpretation of radiologists to assess its utility as a COVID-19 triage tool. Material(s) and Method(s): The study was conducted in collaboration with Kaushalya Medical Trust Foundation Hospital, Thane, Maharashtra, between July and August 2020. We used a collection of public and private datasets to train our AI models. Specificity and sensitivity measures were used to assess the performance of the AI algorithm by comparing AI and radiology predictions using the result of the reverse transcriptase-polymerase chain reaction as reference. We also compared the existing open-source AI algorithms with our method using our private dataset to ascertain the reliability of our algorithm. Result(s): We evaluated 611 scans for semantic and non-semantic features. Our algorithm showed a sensitivity of 77.7% and a specificity of 75.4%. Our AI algorithm performed better than the radiologists who showed a sensitivity of 75.9% and specificity of 75.4%. The open-source model on the same dataset showed a large disparity in performance measures with a specificity of 46.5% and sensitivity of 91.8%, thus confirming the reliability of our approach. Conclusion(s): Our AI algorithm can aid radiologists in confirming the findings of COVID-19 pneumonia on chest radiography and identifying additional abnormalities and can be used as an assistive and complementary first-line COVID-19 triage tool.Copyright © Cancer Research, Statistics, and Treatment.

Pectoralis muscle area measured at T4 level is closely associated with adverse COVID-19 outcomes in hospitalized patients.

OBJECTIVES: Skeletal muscle area (SMA) at T4 level on chest computed tomography (CT) is a newly available method that can be used as a surrogate sarcopenia marker. The objective of this study is to evaluate association of SMA with adverse COVID-19 outcomes in hospitalized patients. METHODS: Hospitalized COVID-19 patients were prospectively recorded in a database containing age, gender, date of admission, date of outcome (discharge, mortality, presence of intensive care unit (ICU) stay, additional coding information (comorbidities, superimposed conditions). Admission CT-scans were retrospectively evaluated for segmentation (bilateral pectoralis major/minor, erector spinae, levator scapulae, rhomboideus minor and major and transversospinalis muscles) and SMA calculation using 3-D slicer software. RESULTS: 167 cases were evaluated (68 male, 72 female, 140 survived, 27 dead). Muscle area was lower in patients with ICU stay (p=0.023, p=0.018, p=0.008) and mortality outcome (p=0.004, p=0.007, p=0.002) for pectoralis, back and SMA. In multivariate Cox-regression analysis, hazard ratio (HR) value for the pectoralis muscle area value below 2800 mm2 was found to be 3.138(95% CI: 1.171-8.413) for mortality and 2.361(95% CI: 1.012-5.505) for ICU. CONCLUSIONS: Pectoralis muscle area measured at T4 level with 3-D slicer was closely associated with adverse outcomes (mortality, ICU stay) in hospitalized COVID-19 patients. Since early treatment methods for COVID-19 are being evaluated, this method may be a useful adjunct to clinical decision making in regard to prioritization.

Using DTI tractography to guide tDCS interventions in a complex acquired brain Injury neurorehabilitation protocol - a case report

51-year-old man (C.P.) had a diffuse-axonal-injury after falling from a 5-meter height, followed by a 22-minute anoxia due to a cardiac arrest. In the ICU, he tested positive to COVID-19, and needed intubation. After coronavirus infection, C.P. presented Guillain-Barre syndrome. 2months after discharge, he was admitted to rehabilitation. DTI tractography for evaluation of the structural integrity of white matter tracts revealed: i) Lesions in the basal ganglia;ii) Sequelary lesions in the right frontal, cortical, subcortical, temporal, parieto-occipital and cerebellar hemispheres;iii) Asymmetry of the corticospinal tracts - less fibers on the left;iv) Poor definition of the fibers of the right arcuate fasciculus;v)Asymmetrical thinning of the cortico-ponto-cerebellar tracts, worse on the left, and more discreetly in the spinocerebellar tracts. Based on this, C.P. underwent 4 different 30-session tDCS protocols consisting of twice-daily 20min 2mA sessions (10min interval), 5days/week (120sessions total), combined with physiotherapy, cognitive, swallowing and speech therapy. Montages: Pr1 (anode: Cz - 5x10cm;cathode: 10th Thoracic Vertebra - 5x7cm);Pr2 (1 - anode:C3;cathode:Fp2 / 2 - anode: Cerebellum;cathode:Fp2);Pr3 (anode:F3;cathode:Fp2) and Pr4 (anode:Cp5;cathode:Fp2). Except for Pr1, electrode size for all protocols were 5x7cm. We used the Coma Recovery Scale (CRS-R) and Rancho Los Amigos Scale (RLAS) for clinical assessments at the baseline and after every 10 sessions until the end of the intervention. At the baseline, C.P. presented a minimal responsive state of consciousness (CRS-R: 3;RLAS: Level 1) and tolerated well the tDCS interventions. CRS-R scores gradually improved in various domains during the treatment. At the end, RLAS score was level 5 and CRS-R, 19. Our preliminary results suggest DTI tractography may be a potential biomarker to guide more personalized tDCS interventions for complex cases of patients with acquired brain injuries. A second DTI tractography will be made in the future for comparison purposes. Research Category and Technology and Methods Clinical Research: 9. Transcranial Direct Current Stimulation (tDCS) Keywords: Acquired Brain Injury, Traumatic Brain Injury, COVID-19, Guillain Barre SyndromeCopyright © 2023

MERALGIA PARESTHETICA CAUSED BY THORACOLUMBAR BRACE IN CONSERVATIVELY TREATED THORACOLUMBAR FRACTURES

Objective: Lateral femoral cutaneous neuropathy or meralgia paresthetica (MP) occurs for various reasons. MP developing after spine surgery is not uncommon and is mostly due to the prone position during surgery or iliac graft harvesting. However, it is usually overlooked due to mild symptoms and a self-limiting course. The purpose of this study was to present a case series of five patients who were followed up with conservative treatment for vertebral fractures and developed MP after prolonged use of lumbar braces. Materials and Methods: The sample comprised five patients with thoracolumbar fractures who did not meet the surgical criteria of the Thoracolumbar Injury Classification and Severity score and who were advised to use lumbar braces for 8 weeks and to return to the outpatient department. These patients did not present for follow-up due to the coronavirus disease-2019 (COVID-19) pandemic and continued to use the lumbar brace for more than the advised 8 weeks. A retrospective evaluation of age, sex, body mass index (BMI), comorbidities, and duration of brace use was conducted. Results: Three of the five patients were male with an average age of 61±18 years, average BMI of 29.3±4.8 kg/m2, (after excluding the young and normal-weight patient, the average age and BMI increased to 70±5 years and 31.6±1.5 kg/m2, respectively), and an average brace use duration of 18.4±3.2 weeks. Three patients presented with MP on the left side. Conclusion: Although tight-fitting pants/corsets/belts/body armor can cause MP, no cases of MP caused by lumbar braces used for conservative treatment of vertebral fractures have been reported. This case series arose from the effects of COVID-19, as the patients wanted to stay home. ©Copyright 2021 by the Turkish Spine Society / The Journal of Turkish Spinal Surgery published by Galenos Publishing House.

Multimodality imaging workup of classical Hodgkin lymphoma in an 8-month-old child.

The incidence of Hodgkin lymphoma (HL) varies by age, most commonly affecting 15-19-year-olds. Cases in children less than 3 years old are exceedingly rare. We report a case of classical HL in an 8-month-old male; the youngest case reported thus far in the literature to our knowledge. Furthermore, while lymphadenopathy is a salient feature of HL, it was absent in our patient, who presented with immunodeficiency and delays in achieving neurologic milestones. A thorough radiologic workup demonstrated bilateral paravertebral masses, collapse of the T3 vertebrae, and severe spinal cord compression. Involvement of the lung, liver, and spleen was also noted. Histopathological evaluation of the paravertebral mass revealed a diagnosis of classical HL. Various non-neoplastic and malignant disorders, such as tuberculosis, Langerhans cell histiocytosis, leukemia, and neuroblastoma, amongst others, could be included in the differential diagnosis of our patient. Using an Illustrative case report, we review the multimodality imaging workup of Hodgkin lymphoma.

INTRAMEDULLARY GAS: A NEW FEATURE THAT PORTENDS A POOR PROGNOSIS IN COVID-19?

SESSION TITLE: Lessons Learned from Critical Care Cases SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Air outside the lungs, bowel, or paranasal cavities suggests critical pathology. Pneumoperitoneum is a classic example in which free abdominal air may signify hollow viscus injury and the need for emergent surgical management. Ectopic gas can also be secondary to barotrauma secondary to mechanical ventilation and concurrent lung injury;the latter being findings often observed in COVID pneumonia (1,2,3). Our case of extensive intramedullary gas in the setting of COVID pneumonia is an example of extensive dissecting air related to barotrauma, but also illustrates how it mimics dire cases of pneumoperitoneum. Therefore, it is an imaging finding that intensivists caring for COVID pneumonia patients should be aware of. CASE PRESENTATION: A 52-year-old male with mild restrictive lung disease from congenital scoliosis developed COVID pneumonia and hypoxic respiratory failure requiring intubation. Clinical course was complicated by renal failure, deep venous thromboses, and radial artery occlusion. CT evaluation revealed large volume upper abdominal pre-peritoneal gas, pneumoperitoneum, soft tissue and intramedullary gas within bilateral ribs and multiple vertebral bodies. Despite reassuring abdominal exams, the patient deteriorated. The patient was placed on comfort care and expired. DISCUSSION: Intramedullary gas refers to the presence of air within the cortical or trabecular bone, bone marrow, or medullary cavity. It is an exceedingly rare imaging finding which was first described in ischemic vertebral collapse and osteomyelitis (4,5). Differential diagnosis includes infection, trauma, degenerative and iatrogenic causes (5,6). Embryologically, fascial layers of the thorax and periosteal coverings of the thoracic osseous structures are derived from the mesoderm, thus creating a continuum between the lungs, surrounding soft tissues, peritoneum, and surrounding osseous structures, and therefore allowing gas to travel between the lung and intramedullary space (7). As cases of COVID pneumonia with ARDS increase, we are becoming aware of the increasing incidence of ectopic air, and the poor prognosis and increased mortality that results (1). Therefore, the finding of intramedullary gas is an important prognostic indicator that the clinician should be aware of. CONCLUSIONS: Several recent studies demonstrate increased mortality in COVID patients who develop ectopic gas as a result of barotrauma and/or acute lung injury (1,2,3). As such the clinician should be aware of these findings, which include pneumomediastinum, subcutaneous emphysema, pneumoperitoneum, pre-peritoneal air, and intramedullary gas for early recognition. Reference #1: 1. Lemmers DHL, Abu Hilal M, Bnà C, Prezioso C, Cavallo E, Nencini N, Crisci S, Fusina F, Natalini G. Pneumomediastinum and subcutaneous emphysema in COVID-19: barotrauma or lung frailty? ERJ Open Res. 2020 Nov 16;6(4):00385-2020. doi: 10.1183/23120541.00385-2020. PMID: 33257914;PMCID: PMC7537408. Reference #2: 2. Guven BB, Erturk T, Kompe Ö, Ersoy A. Serious complications in COVID-19 ARDS cases: pneumothorax, pneumomediastinum, subcutaneous emphysema and haemothorax. Epidemiol Infect. 2021 Jun 8;149:e137. doi: 10.1017/S0950268821001291. PMID: 34099076;PMCID: PMC8207553. Reference #3: 3. Tetaj N, Garotto G, Albarello F, Mastrobattista A, Maritti M, Stazi GV, Marini MC, Caravella I, Macchione M, De Angelis G, Busso D, Di Lorenzo R, Scarcia S, Farina A, Centanni D, Vargas J, Savino M, Carucci A, Antinori A, Palmieri F, D'Offizi G, Ianniello S, Taglietti F, Campioni P, Vaia F, Nicastri E, Girardi E, Marchioni L, Icu Covid-Study Group. Incidence of Pneumothorax and Pneumomediastinum in 497 COVID-19 Patients with Moderate-Severe ARDS over a Year of the Pandemic: An Observational Study in an Italian Third Level COVID-19 Hospital. J Clin Med. 2021 Nov 29;10(23):5608. doi: 10.3390/jcm10235608. PMID: 34884310;PMCID: PMC8658701. DISCLOSURES: Researc support relationship with 4D Medical Please note: March 2021 Added 04/04/2022 by Anu Brixey, value=Grant/Research Support No relevant relationships by raluca mccallum

METASTATIC BLADDER PARAGANGLIOMA WITH UNDERLYING SHDB MUTATION

Introduction Phaeochromocytoma and paraganglioma (PPGL) are rare tumors with up to 40% associated with inherited germline mutations. SHDB mutation is associated with an increased risk of metastasis. Case A 36-year-old male presented with hypertensive emergency. He was diagnosed to have a bladder paraganglioma at age 32 when he presented with hypertensive crisis. Ga-68 DOTANOC PET/CT scan then showed a localized 4.7 x 5.3 cm bladder paraganglioma and he underwent complete surgical resection with resolution of his symptoms. Genetic testing done showed SHDB, deletion (exon 1), heterogenous pathogenic variant. He remained asymptomatic and was lost to follow-up due to COVID-19 until his recent admission. During this admission, he had labile blood pressure with symptoms of palpitations and lethargy. He was found to have a 4.3x elevated urine normetanephrine (1639 ug/day, N<374.7). Metanephrine and 3-methoxytyramine levels were normal. His blood pressure was controlled with phenoxybenzamine 20 mg TDS (1 mg/kg), telmisartan 40 mg OM and carvedilol 25 mg BD with improvement in his symptoms. Subsequent anatomical imaging with CT and functional imaging with Ga-68 DOTATATE showed a small recurrence at the bladder wall with metastatic lesions at the left sacral ala measuring 4.5 x 5.1 cm, and multiple lytic lesions over the spine, ribs and also the left acetabulum with the highest uptake of Ga-68 DOTATATE at the C2 vertebra (SUV max 93). He is now planned for peptide receptor radionuclide therapy (PRRT). SHDB mutation is associated with a higher risk of metastatic disease which has remained unexplained. Treatment for metastatic disease include surgical resection where possible, targeted therapy such as PRRT, meta-iodobenzylguanidine (MIBG) therapy, radiotherapy and also systemic therapy such as chemotherapy and tyrosine kinase inhibitors. Conclusion Patients with PPGL, especially those with SHDB mutation, require monitoring at regular intervals to screen and detect metastasis to reduce mortality and morbidity.

Cervical Staphylococcus aureus Infection after Receiving the Third Dose of COVID-19 Vaccination: A Case Report.

INTRODUCTION: Vaccination is one of the most effective ways to control the COVID-19 pandemic. However, as the number of people vaccinated against COVID-19 continues to increase, there are more reports on the safety of vaccines. So far, there have been no reported cases of spinal infection associated with COVID-19 vaccination. Recently, we admitted a patient who developed cervical Staphylococcus aureus infection resulting in high paraplegia after receiving the third dose of COVID-19 vaccine when the symptoms of cold did not completely disappear. CASE PRESENTATION: The patient was a 70-year-old man who received the third injection of COVID-19 vaccine when the cold symptoms were not completely gone. On the day after the injection, the patient developed severe neck and shoulder pain, accompanied by numbness and fatigue in the limbs. MRI examination of the cervical spine on day 6 after vaccination showed no obvious signs of infection. The patient had progressive weakness in the extremities. On the ninth day after vaccination, the patient developed paralysis of both lower limbs and significant sensory loss. Cervical abscess and cervical spinal cord injury were considered for cervical CT and MRI examination on the 15th day after vaccination. We used an anterior approach to remove as much of the lesion as possible. Staphylococcus aureus was detected and antibiotic treatment was continued after surgery. The patient's pain symptoms were significantly relieved, which prevented the abscess from further pressing the spinal cord and provided possible conditions for the recovery of neurological function in the later stage. CONCLUSION: This case is the first reported cervical Staphylococcus aureus infection resulting in high paraplegia after receiving the third dose of COVID-19 vaccine with low immunity. This case raises awareness of this rare but potentially life-threatening adverse reaction, and reminds people to hold off when their immune system is weakened.

THE ELDEST HEART TRANSPLANTED PATIENT IN EUROPE: 36 YEARS SURVIVAL AND STILL GOING ON

Development of endomyocardial biopsy for acute rejection monitoring in the early Seventies, and above all use of cyclosporine in the clinical practice starting from 1980, introduced the modern era of heart transplantation. Following the initial positive outcomes, the first Italian transplant was performed in Padua by V.Gallucci on November 15th 1985. This pioneering success was rapidly repeated in Pavia, where M.Viganò performed the second transplant on Novembre 17th. Recipient was 20 years old man, suffering from dilated cardiomyopathy, on urgent transplant list. Cardiac index was 1.38 l/min/m2 and pulmonary vascular resistance 1.6 WU. Donor was a 14 years old boy died of brain injury. Total ischemic time was 125 minutes. Induction immunosuppression consisted of horse anti-lymphocyte immunoglobulins, whereas maintenance therapy included cyclosporine, azathioprine and steroids. Postoperative course was complicated by pericardial effusion and cholestatic jaundice. Later pulmonary aspergillosis occurred and due to the profound immunodepression was complicated by fungal localization at L2 vertebral body. The infection was treated with surgical removal of the secondary localization and amphotericin B administration. On December 6th severe acute rejection was found at biopsy and treated with i.v. steroid pulse. Length of ICU and hospital stay was 28 and 72 days, respectively. In 1998 HCV infection was detected and eradicated in 2017 with elbasvir/grazoprevir therapy. Complications of long term immunosuppressive treatment included dyslipidemia, myeloma and basal cell carcinoma. Due to long-term calcineurin inhibitors therapy progressive chronic renal failure occurred, leading to replacement therapy in 2015 and kidney transplantation in 2016. In 2015 the patient underwent percutaneous coronary intervention with stents implantation in two marginal branches and in the anterior descending artery in 2021. Everolimus was introduced to slow down progression of cardiac allograft vasculopathy. In 2020 he suffered from Covid-19, but the course of infection was uneventful being cough the only symptom. We report the eldest survivor after heart transplant in Europe. Our case demonstrates that despite early and long-term complications of immunosuppressive therapy, a careful and patient tailored management allowed an amazing outcome. Nowadays heart transplant remains the best treatment for end stage heart failure and allows to resume a nearly normal quality of life.

CHEST CT BODY COMPOSITION CHANGES at 3 and 6 MONTHS after SEVERE COVID-19 PNEUMONIA

Background: Muscle and fat mass loss as a consequence of protein catabolism and prolonged immobilization is frequent in critically ill patients. Post-COVID acute sarcopenia may be due also to inflammaging for the strong inflammatory reaction. The study aims were to describe changes in chest CT body composition parameters from baseline to follow-up CT scan in severe COVID-19 survivors, and to evaluate the impact of COVID-19 inflammatory burden on these changes. Methods: Baseline (t0), 2-3 months (t1) and 6-7 months (t2) follow-up CT scan of severe COVID-19 pneumonia survivors were retrospectively reviewed to measure pectoralis muscle area (PMA) and density (PMD), liver-to-spleen ratio (LSR), and total, visceral, and intermuscular adipose tissue areas (TAT, VAT and IMAT) at T7-T8 vertebrae. C-reactive protein (CRP) curve integral was used to describe COVID-19 inflammatory burden, and its impact on body composition changes was evaluated in multivariable linear regression models adjusted for age, sex, and baseline TAT (index of general adiposity). Results: At follow-up a decrease in mean PMA and in all mean body fat areas was registered, faster from t0 to t1, and slower from t1 to t2, with the exception of PMD, which increased (i.e. intramuscular fat decreased) only from t1 to t2 (Table). Mean VAT decrease was more conspicuous than mean TAT decrease. In models adjusted for age, sex, and baseline TAT, increasing CRP integral was significantly associated with higher PMA reduction (p=0,017 for delta t2-t0) and lower PMD increase (p=0.01 for delta t2-t0), higher LSR increase (i.e. higher steatosis decrease) (p<0.0001 for delta t1-t0, n.s. for delta t2-t0), and higher VAT decrease (p=0.035 for delta t2-t0), but not with TAT decrease. These associations were stronger in patients with higher VAT and lower LSR at baseline. Conclusion: Muscle and fat loss after COVID-19 is faster in the first months, but slowly continues till 6-7 months. Fat loss is more apparent in visceral compartments. Inflammatory burden is associated with the degree of muscle and visceral/liver fat loss.

Association of Salivary IGF and IGF/IGFBP-3 Molar Ratio with Cervical Vertebral Maturation Stages from Pre-Adolescent to Post-Adolescent Transition Period—A Cross-Sectional Exploratory Study

Background: The relevance of growth determination in orthodontics is driving the search for the most precise and least invasive way of tracking the pubertal growth spurt. Objectives: The aim was to explore whether minimally invasive salivary estimation of biomarkers Insulin-like growth factor (IGF-1) and Insulin-like growth factor binding protein-3 (IGFBP-3) could be used to estimate skeletal maturity with diagnostic accuracy, especially in children and adolescent age groups. Subjects and methods: The cross-sectional study was conducted on 105 participants aged 6–25 years from the out-patient Department of Preventive Dental Science at Majmaah University between the period 2 January 2021 and 12 July 2021. Each subject’s lateral cephalogram radiograph was categorized based on skeletal maturity, and saliva samples were estimated for IGF-1 and IGFBP-3 using the respective ELISA kits. Two-way ANOVA with interaction was applied to examine the main effects due to cervical vertebral maturation staging (CVS), Sex and interaction effect due to CVS, and Sex on study parameters. Karl Pearson’s Product Moment Correlation Coefficient was calculated for finding a significant association between IGF, IGFBP3, and the IGF-1/IGFBP3 molar ratio. Results: Highest mean salivary IGF-1 was observed in the pubertal peak stage, which coincides with cervical vertebral maturity stages 3 and 4 (CVS3 and CVS4) for both males (2.57 ng/mL) and females (1.57 ng/mL) and the lowest mean level of IGF-1 for females (0.85 ng/mL) and males (1.22 ng/mL) was observed during the prepubertal stage. There exists a significant variation in IGF-1 between males and females in the pubertal stage (p < 0.01), but the difference is very narrow in the prepubertal and post-pubertal groups (p > 0.05). There was no significant interaction effect of different skeletal stages and gender on the IGFBP3 and the IGF-1/IGFBP3 molar ratio (p > 0.05), but there exists a significant interaction effect on IGF-1 (p < 0.05). Conclusion: Estimation of the IGF-1 and the IGF-1/IGFBP3 molar ratio in saliva, being a non-invasive biological marker, could serve as an adjunctive tool along with radiographic assessment in estimating growth maturity in the adolescence age group. By initiating orthodontic treatment during the mandibular growth peak in adolescence, a positive outcome is ensured in managing skeletal deformities within the craniofacial complex.

MACHINE LEARNING AND RADIOMICS IDENTIFY NOVEL BIOMARKERS OF BONE LOSS

Purpose: Altered bone turnover is a factor in many diseases including osteoarthritis (OA), osteoporosis, inflammation, and viral infection. The absence of obvious symptoms and insufficiently sensitive biomarkers in the early stages of bone loss limits early diagnosis and treatment. Therefore, it is urgent to identify novel, more sensitive, and easy-to-detect biomarkers which can be used in the diagnosis and prognosis of bone health. Our previous data using standard micro-computed tomography (μCT) measurements showed that SARS-CoV-2 infection in mice significantly decreased trabecular bone volume at the lumbar spine, suggesting that decreased bone mass, increased fracture risk, and OA may be underappreciated long-haul comorbidities for COVID patients. In this study, we applied integrated state-of-the-art radiomics and machine learning models to identify more sensitive image-based biomarkers of SARS-CoV-2-induced bone loss from μCT images. These radiomic biomarkers can potentially provide a non-invasive way of quantifying and monitoring systemic bone loss and evaluating treatment efficacy in both research and clinical practices. Methods: All animal use was performed with approval of the Institutional Animal Care and Use Committee. To quantify SARS-CoV-2-induced bone loss, 6-week-old transgenic mice (16 male, 16 female) expressing humanized ACE2 receptors were inoculated with a 2020 strain of SARS-CoV-2 or phosphate-buffered saline (Control) [Fig. A]. Viral infection was confirmed by detection of infectious SARS-CoV-2 in throat swabs and histological identification of SARS-CoV-2 labeled cells. At 6-14 days post-infection, lumbar vertebral bodies (L5) were scanned with μCT (μCT 35, SCANCO Medical AG;6 μm nominal voxel size). The open-source research platform 3D Slicer v2020 with a built-in Python console v3.8 was used for medical image computing and fully automated segmentation of cortical and trabecular bone. Standard μCT assessment of bone microstructure was performed. Radiomic feature extraction and data processing were performed using python based PyRadiomics v3.0.1. A total of 120 radiographic features were extracted from the segmented images [Fig. B]. Principle component analysis (PCA) for feature selection, a support vector machine learning (SVML) predictive model for classification, holdback method for model validation, and all statistical analyses (significance at p<0.05) were performed using JMP Pro v15 (SAS). Results: Using standard μCT methods, SARS-CoV-2 infection significantly reduced the bone volume fraction (BV/TV) by 10 and 10.5% (p= 0.04) and trabecular thickness (Tb.Th) by 8 and 9% (p= 0.02) in male and female mice, respectively, compared to PBS control mice [Fig. C]. Radiomics detected a 20-fold greater magnitude in change over standard methods. SARS-CoV-2 infection significantly changed radiographic parameters with the largest change being a 300% increase in the second-order parameter: cluster shade [Fig. D]. The 45 radiomic features comprising the first 3 principal components were selected for inclusion in the SVML model. The SVML Model (radial basis function kernel;cost = 4.8;gamma = 0.46) produced an area under the receiver operating characteristic curve (AUC) of 1.0 which reflects a perfectly accurate test [Fig. E]. Conclusions: SARS-CoV-2 infection of humanized ACE2 expressing mice caused significant bone changes, suggesting that decreased bone mass, increased fracture risk, OA, and other musculoskeletal complications could be long-term comorbidities for people infected with COVID-19. We developed an open-source, fully automated segmentation and radiomics system to assess systemic bone loss using μCT images. When coupled with machine learning, this system was able to identify novel radiographic biomarkers of bone loss that better discriminate differences in bone microstructure between SARS-CoV-2 infected and control mice than standard bone morphometric indices. The high accuracy of the SVML model in classifying SARS-CoV-2 infected mice opens the possibility of translating these biom rkers to the clinical setting for early detection of skeletal changes associated with long-haul COVID. The methods presented here were demonstrated using SARS-CoV-2 as a model system and can also be adapted to other diseases associated with altered bone turnover. Development of machine-learning methods for radiomic applications is a crucial step toward clinically relevant radiomic biomarkers of bone health and provides a non-invasive way of quantifying and monitoring systemic bone loss and evaluating treatment efficacy. [Formula presented]

Impact of long-term systemic corticosteroids on bone mineral density during diffuse infiltrating lung disease

Objective: To assess the impact of systemic corticosteroid therapy (SCT) indicated in the treatment of diffuse infiltrating lung disease (DILD) on the BMD assessed by bone densitometry Methods: Prospective study conducted in the pneumology department of Mongi Slim-La Marsa Hospital for one year (2019), involving patients with DILD in whom SCT was indicated in association with preventive measures (calcium and vitamin D). After written consent, each patient had the first measurement of BMDbefore starting SCT and then a control measure between 6 and 12 months after the start of treatment Results: 28 patients were enrolled (medium age=55.8 y;sex ratio F/H=3.5). All had the first measure of BMD and only 12 had a control measure (interruption due to COVID-19 pandemic). In the remaining group, the DILD treated were related to sarcoidosis (n=4), idiopathic nonspecific interstitial lung disease (n=3), Gougerot Sjögren's syndrome (n=2), HSP (n=1), Myositis (n=1), and Systemic Lupus Erythematosus (n=1). The average dose of prescribed SCT was 0.75 mg/kg/d. Based on the measurement of the L1-L4 vertebrae, at the first measurement of the BMD, 4 patients had no abnormalities, 3 had osteopenia and 5 had osteoporosis while at the control measure, 3 patients had no abnormalities, 3 had osteopenia and 6 had osteoporosis. Based on the measurement of the right femur, at the first measurement of the BMD, 5 patients had no abnormalities, 5 had osteopenia and 2 had osteoporosis while at the control measure, 3 patients had no abnormalities, 6 had osteopenia and 3 had osteoporosis. This difference between initial and control BMD was significant for the measurement at the right femur (p=0.001). Age was correlated with the decline of BMD in the L1-L4 vertebrae (p=0.024) Conclusion: SCT is responsible for a significant decrease in BMD despite preventive measures, hence the importance of routine osteoporosis screening and collaborative management with rheumatologists.