Bone Marrow Changes Research Articles

Translational Research on Azacitidine Post-Remission Therapy of Acute Myeloid Leukemia in Elderly Patients (QOL-ONE Trans-2).

The achievement of complete remission (CR) is crucial for acute myeloid leukemia (AML) patients undertaking curative therapy, but relapse often occurs within months, highlighting the need for strategies to prolong disease-free survival (DFS). Our phase III study compared the efficacy and safety of azacitidine (AZA) to best supportive care (BSC) in elderly AML patients who achieved CR following intensive induction and consolidation therapy. This ancillary study (QOL-ONE Trans-2) evaluated biological changes in bone marrow using Next-Generation Sequencing (NGS). We analyzed baseline, randomization, and 6-month post-remission samples from 24 patients (median age of 71 and 12 males). High-throughput NGS targeted 350 myeloid malignancy-related genes, considering variants with a variant allele frequency ≥ 4%. At diagnosis, all patients had 5 to 17 (median = 10) mutations, with DNMT3A (42%), NPM1 (33%), and TET2 (33%) being most frequent. FANCA mutations in four patients were linked to a higher relapse risk (HR = 4.96, p = 0.02) for DFS at both 2 and 5 years. Further HLA-specific NGS analyses are ongoing to confirm these results and their therapeutic implications.

Secondary haematological dysplasia after CAR-T-cell therapy foracute lymphoblastic leukaemia in children.

The use of CAR-T is becoming more widespread in the treatment of haematological malignancies. In adults, secondary myelodysplastic syndromes (MDS) after CAR-T have been described. However, there are currently no data on the risk of MDS following CAR-T in children treated for acute lymphoblastic leukaemia (ALL). We studied all children treated with CAR-T cells at Hospital Sant Joan de Déu in Barcelona and those with persistent cytopenias were evaluated at the cytological, cytogenetic, and molecular levels to look for MDS. A total of 106 patients received CAR-T for ALL. Among 40 patients without early relapse or subsequent therapy after CAR-T, four fulfilled the WHO criteria for myelodysplasia. These four patients had received a haematopoietic stem cell transplantation (HSCT) prior to CAR-T and presented cytopenias with severe dysplastic changes in bone marrow after CAR-T. One patient had clonal MDS with high-risk cytogenetics arising from the host cells requiring a HSCT. Three patients had non-progressive dysplasia arising from the donor cells. Two are alive in complete remission with stable cytopenias and one succumbed to ALL relapse. This is the first description of post-CAR-T MDS and haematological dysplasia in children and highlights the need to monitor children with persistent post-CAR-T cytopenias.

Hematological picture of pediatric Sudanese patients with visceral leishmaniasis and prediction of leishmania donovani parasite load.

Visceral leishmaniasis (VL) is a systemic protozoan infection caused by Leishmania donovani (L. donovani) and transmitted by sand flies, causing macrophage invasion in the liver, spleen, and bone marrow. Diagnosis of VL is currently based on clinical signs, symptoms, and specific in-vitro markers and bone marrow investigations. However, VL's specific hematological and bone marrow manifestation in Sudanese pediatric patients is not well studied. To examine the blood and bone marrow characteristics in pediatric patients from Sudan who have VL. This is a retrospective hospital-based study with a sample of 107 consecutive Sudanese pediatric patients. The data focused on hematological and bone marrow results. We included only the completed records of the pediatric patients with VL in the Tropical Disease Teaching Hospital in Khartoum, Sudan from the period of 2016 to 2020. The majority of pediatric patients included in this study are below 5-years-old (n = 59, 55.2%). Moreover, anemia, thrombocytopenia, and leukopenia were among the prevalent characteristics in the population under study. To further analyze the data, we developed a machine learning model using boosted forest algorithms to predict L. donovani parasites load, with a mean accuracy of 0.88 for the training dataset and an accuracy of 0.46, 0.50, and 0.74 for mild, moderate, and severe L. donovani parasite load in the validation dataset. This study shows that the most common bone marrow change among Sudanese VL children was increased chronic inflammatory cells (n = 88, 82.2%) with present macrophage hemophagocytes (n = 103, 96.3%). While anemia and thrombocytopenia were the most common hematological changes. These results will hopefully lead to an early diagnosis and hence better management for Sudanese pediatric patients with suspected VL.

Protective Effect of Endogenous ω-3 Polyunsaturated Fatty Acid Against Cisplatin Induced Myelosuppression

To investigate the protective effect of endogenous ω-3 polyunsaturated fatty acid (PUFA) against cisplatin-induced myelosuppression and the mechanism of reducing apoptosis in bone marrow nucleated cells using mfat-1 transgenic mice. The experimental animals were divided into 4 groups: wild-type mice normal control group, mfat-1 transgenic mice normal control group, wild-type mice model group and mfat-1 transgenic mice model group. The mice in the model group were injected intraperitoneally with 7.5 mg/kg cisplatin on day 0 and day 7 to construct a myelosuppression model, while the mice in the normal control group were injected intraperitoneally with an equal amount of saline, and their status was observed and their body weight was measured daily. Peripheral blood was taken after 14 day for routine blood analysis, and the content and proportion of PUFA in peripheral blood were detected using gas chromatography. Bone marrow nucleated cells in the femur of mice were counted. The histopathological changes in bone marrow were observed by histopathological staining. The apoptosis of nucleated cells and the expression level changes of apoptosis-related genes in the bone marrow of mice were detected by flow cytometry and fluorescence quantitative PCR. Compared with wild-type mice, mfat-1 transgenic mice showed significantly increased levels of ω-3 PUFA in peripheral blood and greater tolerance to cisplatin. Peripheral blood analysis showed that endogenous ω-3 PUFA promoted the recovery of leukocytes, erythrocytes, platelets and haemoglobin in peripheral blood of myelosuppressed mice. The results of HE staining showed that endogenous ω-3 PUFA significantly improved the structural damage of bone marrow tissue induced by cisplatin. Flow cytometry and PCR showed that, compared with wild-type mice model group, the apoptosis rate of bone marrow nucleated cells in mfat-1 transgenic mice was significantly reduced ( P < 0.001), and the expression of anti-apoptotic genes Bcl-2 mRNA was significantly increased ( P < 0.01), while the expressions of pro-apoptotic genes Bax and Bak mRNA were significantly reduced ( P < 0.001, P < 0.05). Endogenous ω-3 PUFA can reduce cisplatin-induced apoptosis in bone marrow nucleated cells, increase the number of peripheral blood cells and exert a protective effect against cisplatin-induced myelosuppression by regulating the expression of apoptosis-related genes.

Bone Marrow and Peripheral Blood Mononuclear Cell Phenotype Changes after Cultivation and Autologous Infusion in Patients with Primary Biliary Cholangitis.

Primary biliary cholangitis (PBC) is a condition affecting the liver and immune system. In this study, the impact of autologous bone marrow-derived mononuclear cell (BM-MNC) transplantation on PBC patients was investigated. Sixteen eligible PBC patients participated at the National Scientific Medical Center in Astana, Kazakhstan, between 2017 and 2022, and BM-MNCs were harvested from their anterior iliac crest. After isolating and cultivating the BM-MNCs, they were infused back into the patient's peripheral veins. Changes in BM-MNC and peripheral blood mononuclear cell (PB-MNC) phenotypes were assessed before and after a 24-hour cultivation period and 72 hours post-transplantation. We monitored liver function parameters over 6-month intervals and conducted flow cytometry analysis to assess CD markers on BM-MNCs before and after cultivation and PB-MNCs before and after transplantation. Statistical analysis included the Friedman test for liver parameters and the Wilcoxon signed-rank test for BM-MNC and PB-MNC comparisons. Our findings revealed significant reductions in liver function tests after multiple transplantations. Flow cytometry analysis before and after a 24-hour culture and autologous BM-MNC infusion revealed the expansion of specific cell populations, with significant increases in CD3+, CD4+, CD16+, CD20+, CD25+, CD34+, CD105+, CD73+, СD117+, and CD34+populations, while CD4+25+, CD34+105+, and CD4+FOXP3+ populations decreased. Interestingly, a contradictory finding was observed with a decrease in bone marrow CD34+105+ cell lines (P=0.03) alongside an increase in peripheral CD34+105+ population (P=0.03). In summary, our study shows that BM-MNC transplantation in PBC patients leads to changes in immune cell populations and liver function. These findings suggest potential therapeutic applications of BM-MNC transplantation in managing PBC and offer insights into the dynamics of immune cells associated with this treatment approach.

Diagnostic Value of Whole-Body MRI in Pediatric Patients with Suspected Rheumatic Diseases.

Background and Objectives: The diagnosis of rheumatic diseases in children is challenging and requires the use of advanced imaging examinations such as whole-body magnetic resonance imaging (MRI). Whole-body MRI allows visualization of bone marrow edema (BME), muscle edema, joint effusion and changes in the soft tissues surrounding the joints. The aim of this study was to collect and compare whole-body MRI findings, laboratory results and clinical manifestations of pediatric patients with suspected rheumatic disease. Materials and methods: In this retrospective single-center study, 33 patients who underwent whole-body MRI were included. Their age ranged from 9 to 17 years, and 24 (72.73%) of the patients were female. Patients were diagnosed as follows: juvenile idiopathic arthritis (27.27%), juvenile idiopathic inflammatory myopathies (21.21%), chronic nonbacterial osteomyelitis (21.21%) and other medical conditions (30.30%), such as arthritis associated with infection, scleroderma, Takayasu arteritis, polyarteritis nodosa and joint damage. Results: The most common symptom reported by 26 (79.79%) patients was pain. On physical examination, the limitation of joint mobility was examined in 17 (51.51%), swelling of the joints was observed in 12 (36.36%) patients and decreased muscle strength was noticed in 11 (33.33%) patients. An increase in the C-reactive protein (12%), erythrocyte sedimentation rate (9%), leukocyte count (9%) and creatine kinase (CK) (18%) was observed. Whole-body MRI revealed myositis (30%), joint effusion (27%) and BME (24%). The statistical analysis showed a significant relationship between myositis and the elevated CK level (p < 0.05). Conclusions: The most common symptom in the studied population was pain, while the limitation of joint mobility was found in more than half of patients. Myositis was the most commonly imaged lesion on the whole-body MRI and it was related to an increase in the CK level.

Multimodality imaging of bone marrow involvement in paediatric oncology

Identifying bone marrow involvement (with or without bone destruction) in children with cancer is essential for adequate diagnosis, prognostication, therapy planning, and response assessment. Imaging plays an increasing role, with MRI including DWI and [18F]FDG-PET/CT as the most commonly used imaging techniques. Interpretation of the paediatric bone marrow on imaging might be challenging because of age-related physiological changes in the bone marrow, as well as disease and therapy related effects. In this review, we discuss how the imaging techniques available may be employed to detect bone marrow involvement (BMI) in paediatric oncology. Furthermore, insights into physiological, disease and therapy related bone marrow changes in children that might influence bone marrow imaging interpretation will be provided.

Proteomic screening identifies PF4/Cxcl4 as a critical driver of myelofibrosis.

Despite increased understanding of the genomic landscape of Myeloproliferative Neoplasms (MPNs), the pathological mechanisms underlying abnormal megakaryocyte (Mk)-stromal crosstalk and fibrotic progression in MPNs remain unclear. We conducted mass spectrometry-based proteomics on mice with Romiplostim-dependent myelofibrosis to reveal alterations in signaling pathways and protein changes in Mks, platelets, and bone marrow (BM) cells. The chemokine Platelet Factor 4 (PF4)/Cxcl4 was up-regulated in all proteomes and increased in plasma and BM fluids of fibrotic mice. High TPO concentrations sustained in vitro PF4 synthesis and secretion in cultured Mks, while Ruxolitinib restrains the abnormal PF4 expression in vivo. We discovered that PF4 is rapidly internalized by stromal cells through surface glycosaminoglycans (GAGs) to promote myofibroblast differentiation. Cxcl4 gene silencing in Mks mitigated the profibrotic phenotype of stromal cells in TPO-saturated co-culture conditions. Consistently, extensive stromal PF4 uptake and altered GAGs deposition were detected in Romiplostim-treated, JAK2V617F mice and BM biopsies of MPN patients. BM PF4 levels and Mk/platelet CXCL4 expression were elevated in patients, exclusively in overt fibrosis. Finally, pharmacological inhibition of GAGs ameliorated in vivo fibrosis in Romiplostim-treated mice. Thus, our findings highlight the critical role of PF4 in the fibrosis progression of MPNs and substantiate the potential therapeutic strategy of neutralizing PF4-GAGs interaction.

Role of End Plate Changes and Paraspinal Muscle Pathology in Lower Back Pain: A Narrative Review.

Degenerative changes of the lumbar intervertebral disc are the most significant causes of enduring lower back pain. The possibility of the diagnosis is limited in people with this low back pain. Therefore, it is essential to identify the relevant back pain subgroups. The paraspinal muscles, that is, the muscles that attach to the spine, are necessary for the proper functioning of the spine and the body; insufficiency can result in back pain. Lower back pain disorders are strongly associated with altered function or structure of these paraspinal muscles, especially fibrosis and fatty infiltration. Modic changes are the bone marrow changes of the end plate in the vertebral body seen on MRI. These are strongly related to degeneration of the disc and are common in individuals with back pain symptoms. Articles were selected from Google Scholar using the terms 'Modic changes,' 'end plate changes,' 'paraspinal muscles,' and 'lower back pain. ' This article compiled different studies aiming to enhance the comprehension of biochemical processes resulting in the development of lumbar pain. Search using the keywords 'Modic changes,'' end plate changes lower back pain,' 'paraspinal muscles lower back pain,' and 'Modic changes lower back pain' on Google Scholar yielded 33000, 41000, 49400, and 17,800 results, and 958, 118, 890 and 560 results on Pubmed respectively.

Abstract 2059: Therapeutic Delivery Of MICRORNA-369-3p Promotes Atherosclerosis Regression In Diabetic Mice By Regulating Bone Marrow Myeloid Progenitors

Introduction: Hyperglycemia-induced immunometabolic alterations promote myelopoiesis, increase proinflammatory monocytes, and impair atherosclerosis regression. Identifying critical factors to restore metabolic alterations and promote resolution of inflammation remains an unmet medical need. MicroRNAs (miRs) orchestrate multiple signaling events in macrophages and regulate inflammation. Using miR-seq, we identified miR-369-3p as a novel miR expressed higher in regressing mouse plaques. Hypothesis: Therapeutic administration of miR-369-3p promotes plaque regression of diabetes-associated atherosclerosis in mice. Aim: To identify the therapeutic benefits of miR-369-3p overexpression, and the mechanism by which it promotes plaque regression in diabetic mice. Methods: Ldlr-/ - mice were fed HFSC-diet for 12-weeks to develop atherosclerotic plaques and were switched to chow-diet for 6-weeks to induce regression. During regression, mice received either non-specific control mimic (NS-m) or miR-369-3p mimic (369-m) intravenously twice every week. Immunohistological, morphometric, and flow cytometric analyses were performed to define the changes in plaque, circulation, and bone marrow following 369-m delivery. Results: Therapeutic delivery of 369-m promoted plaque resolution in diabetic mice, evident by reduced plaque area and macrophage content when compared to NS-m injected mice. Circulating proinflammatory cytokines (IL1β, IL6 and TNF-α), total circulating monocytes, and M1 macrophages were decreased in lesions while M2 macrophages were increased in 369-m group. 369-m also increased plaque stability and increased FOXP3+ Tregs in plaques when compared to NS-m group. Bioinformatic analyses showed GPR91 and CEBPB as conserved miR targets. Mechanistically, we found that 369-m decreased bone marrow granulocyte-monocyte progenitor population (GMPs), resulting in less inflammatory monocytes, attributed to reduced CEBPB and GPR91 target expression in GMPs. Conclusion: miR-369-3p overexpression reduced plaque-inflammatory macrophages, bone marrow GMPs, and proinflammatory monocytes by regulating macrophage immunometabolism in diabetes-accelerated atherosclerosis in part by targeting CEBPB and GPR91.

Use of Multimodality Imaging in the Evaluation of Patients With Spondyloarthropathies and Sacroiliitis.

Spondyloarthropathy (SpA) is one of the most common causes of low back pain. It is caused by inflammatory arthritis in the spine, manifesting in various forms such as psoriatic arthritis (PsA), ankylosing spondylitis (AS), and sacroiliitis. A comprehensive systematic literature search was done to evaluate and compare MRI, CT, single-photon emission CT, PET, ultrasound (US) imaging, low-dose CT, and diffusion-weighted imaging (DWI) techniques in assessing SpAs. The search strategy was constructed by an analysis of key terms from relevant articles in MEDLINE ProQuest, Embase, and PubMed. The key terms used to search for these articles were "SpA," "sacroiliitis," "spondylitis," "psoriatic arthritis," "MRI," "CT scan," "x-ray," "magnetic resonance imaging," "computed tomography," "bone density," and "ultrasound." A total of 1,131 articles published in English between January 1, 2003, and October 15, 2023 were identified and screened for eligibility by members of the research team, which resulted in 69 total articles selected for the final review. US has played an important role in visualizing joint inflammation and enthesitis (inflammation of the enthesis), which are common features of PsA. Although MRI and CT are considered more reliable modalities for diagnosing active sacroiliitis, US imaging with Doppler flow can also be useful in conjunction with CT images to visualize abnormal blood flow in the sacroiliac joints, as well as other joints affected by inflammatory arthritis. MRI provides increased diagnostic confidence in the diagnosis of sacroiliitis in active AS patients when compared to CT. CT is more sensitive than plain radiographs. The PET activity score showed a good correlation in diagnosing inflammatory sacroiliitis but lacked in identifying structural lesions. CT has high diagnostic accuracy, but it exposes patients to a high radiation dose. MRI visualizes joint and tissue inflammation, bone, and bone marrow change and can identify peripheral inflammation in soft tissue and joints in patients diagnosed with PsA. MRI can also visualize bone marrow changes and subchondral edema, which can aid in the early diagnosis of ankylosing SpA and gauge disease severity. DWI and short-tau inversion recovery imaging are both MRI techniques used in detecting sacroiliitis. MRI and CT are shown to be reliable imaging modalities for the diagnosis of sacroiliitis; however, it was found that Doppler US played an accurate role in the diagnosis as well. MRI visualizes joints and tissue with the most precision, making it useful in evaluating patients with PsA, while PET CT is useful in the diagnosis of inflammatory sacroiliitis patients. There is limited literature available comparing the multiple modalities of imaging available for each SpA. The review's objective is to analyze imaging findings in patients diagnosed with sacroiliitis and SpAs. The findings in this literature review are valuable for properly assessing and diagnosing patients suffering from SpAs.

Comprehensive analysis of myelosuppression of pediatric patients receiving radiotherapy

Pediatric oncology management necessitates distinct strategies for radiotherapy due to the heightened sensitivity of pediatric bone marrow to radiation exposure compared to adults. Therefore, this study aimed to compare the risk of radiation-induced myelosuppression between pediatric and adult patients by analyzing the correlations between gender, age, active marrow distribution, and radiation-induced myelosuppression. The medical records of 49 pediatric patients aged &lt;15 years were retrospectively analyzed. Subgroup analyses based on sex and age were conducted to compare this pediatric patient data with data from adult patients reported in the literature. The observed rate of radiation-induced myelosuppression in the pediatric group was 59.18%, which was approximately twice the rate for the adult group (34%) reported in literature. Notably, the rates of leukopenia and granulocytopenia were observed in 53% and 45% of patients suffering from radiation-induced myelosuppression, respectively, compared to rates of thrombocytopenia and hemoglobinopenia observed in only 10% of patients, indicating that white blood cells and granulocytes are more sensitive indicators of radiation-induced myelosuppression. Our findings revealed that pediatric patients receiving radiotherapy in the head-and-neck regions face a higher risk of radiation-induced myelosuppression than adult patients due to the changes in active bone marrow during childhood development. Therefore, careful consideration of radiation-induced myelosuppression is essential during protocol optimization for pediatric patients receiving radiotherapy outside the pelvic region.

Reliability assessment of the OMERACT whole-body magnetic resonance imaging scoring system for juvenile idiopathic arthritis

Inter-reader reliability of a new scoring system for evaluating joint inflammation and enthesitis in whole body MRI (WBMRI) in juvenile idiopathic arthritis was tested. The scoring system grades 732 item-region combinations of bone marrow and soft tissue changes for commonly involved joints and entheseal sites. Five radiologists rated 17 WBMRI scans through an online rating platform. Item-wise reliability was calculated for 117 items with non-zero scores in >10 % of readings. Interquartile ranges of the five-reader Kappa reliability coefficients were 0.58–0.73 (range: 0.36–0.88) for the joints, 0.65–0.81 (range: 0.39–0.95) for the entheses, and 0.62–0.75 (range: 0.60–0.76) for chronic nonbacterial osteomyelitis-like lesions.

Assessment of the protective effects of pomegranate peel extract and N-acetyl cysteine alone or in combination with Ornipural® against Cadmium-induced bone toxicity in rat

Aim: The present study was conducted to determine the effects of pomegranate peel extract (PPE) and N-acetyl Cysteine (NAC) alone or in their treatment combinations with commercial preparation Ornipural® (ORN) on bone metabolism against experimentally cadmium (Cd)-induced toxicity in rats. Materials and Methods: Totally 36 animals were used in the study including 6 Wistar Albino rats in each group. The animals were assigned to control, Cd, Cd+PPE, Cd+NAC, Cd+PPE+ORN and Cd+NAC+ORN groups. The animals in the groups were euthanized after their blood samples were taken at the end of the 8th week. The bones were subjected to maceration for morphometric and histopathological examinations after euthanasia. Results: The statistically significant differences were determined between the treatment groups and Cd group in terms of histopathological changes (osteoporotic alterations and changes in red bone marrow) and biomarkers (Ca, P and Mg) (P&lt;0.05). Conclusion: Although PPE, NAC and treatment combinations with ORN applied against experimentally induced cadmium toxicity were determined to have positive effects on bone metabolism, it has been thought that carrying out trials by increasing treatment duration and dose would be beneficial to determine definite efficacy of the applied treatment protocols.

MRI imaging pattern of metastasis and tuberculous spondylitis in the spine: serial case report

Background: Tuberculous spondylitis and spinal metastasis manifestations have a similar clinical manifestation. Spinal metastasis prevalence is high in malignant process while tuberculosis is frequent in endemic areas. Back pain, paresthesia, and paralysis are commonly caused by vertebral fractures, soft tissue mass, and spinal canal involvement. The magnetic resonance imaging (MRI) is a useful modality in the pattern differentiation of these diseases. This case series aimed to provide a differentiation between those two diseases using MRI. Case report: In the first case, we presented a 24-year-old female complained of hip pain without history of tuberculosis infection or malignancy. Whole spine MRI showed kyphotic deformity, compression of T9 vertebral body, erosion of anterior aspect T8 and T10 vertebral body, and subligamentous abscess at T7-T12 vertebrae level. Tuberculous infection was proven. The second case was a 39-year-old female complained of leg weakness without complaint of cough or breathing difficulty. Whole spine MRI showed kyphotic thoracic vertebrae, compression T10 vertebral body, destruction of inferior endplate T9 vertebrae, bone marrow changes on thoracic vertebral body, and paravertebral soft tissue mass on anterior T6 to T11 vertebral body. Tuberculosis etiology was proven. The third case was a 51-year-old female that came to the hospital due to waist pain with no history of tuberculosis infection or malignancy. Whole spine MRI revealed T8 and T9 vertebral body compression and bone marrow replacement on cervical, thoracic, and lumbar vertebrae, spinous process of thoracic and lumbar, bilateral posterior rib T4-T5, and soft tissue mass at the posterior T9 vertebrae. In the last case, we presented a 58-year-old male that complianed pain in the back and both legs. Lumbosacral MRI showed compression fracture with signal intensity change on L3 vertebral body, bone marrow replacement on thoracic, lumbar, and sacral vertebrae, expanding to epidural and cause spinal canal stenosis. CT-scan thorax showed lung malignancy proven to be non-small cell lung carcinoma. A spinal biopsy revealed malignant infiltration. Conclusion: Tuberculous spondylitis and metastasis differentiation can be a challenge. Early complaints mostly are back pain, paresthesia, and paralysis. Spine MRI can differentiate the pattern of both diseases and identify the possible etiology.

Machine Learning Algorithm: Texture Analysis in CNO and Application in Distinguishing CNO and Bone Marrow Growth-Related Changes on Whole-Body MRI.

The purpose of this study is to analyze the texture characteristics of chronic non-bacterial osteomyelitis (CNO) bone lesions, identified as areas of altered signal intensity on short tau inversion recovery (STIR) sequences, and to distinguish them from bone marrow growth-related changes through Machine Learning (ML) and Deep Learning (DL) analysis. We included a group of 66 patients with confirmed diagnosis of CNO and a group of 28 patients with suspected extra-skeletal systemic disease. All examinations were performed on a 1.5 T MRI scanner. Using the opensource 3D Slicer software version 4.10.2, the ROIs on CNO lesions and on the red bone marrow were sampled. Texture analysis (TA) was carried out using Pyradiomics. We applied an optimization search grid algorithm on nine classic ML classifiers and a Deep Learning (DL) Neural Network (NN). The model's performance was evaluated using Accuracy (ACC), AUC-ROC curves, F1-score, Positive Predictive Value (PPV), Mean Absolute Error (MAE) and Root-Mean-Square Error (RMSE). Furthermore, we used Shapley additive explanations to gain insight into the behavior of the prediction model. Most predictive characteristics were selected by Boruta algorithm for each combination of ROI sequences for the characterization and classification of the two types of signal hyperintensity. The overall best classification result was obtained by the NN with ACC = 0.91, AUC = 0.93 with 95% CI 0.91-0.94, F1-score = 0.94 and PPV = 93.8%. Between classic ML methods, ensemble learners showed high model performance; specifically, the best-performing classifier was the Stack (ST) with ACC = 0.85, AUC = 0.81 with 95% CI 0.8-0.84, F1-score = 0.9, PPV = 90%. Our results show the potential of ML methods in discerning edema-like lesions, in particular by distinguishing CNO lesions from hematopoietic bone marrow changes in a pediatric population. The Neural Network showed the overall best results, while a Stacking classifier, based on Gradient Boosting and Random Forest as principal estimators and Logistic Regressor as final estimator, achieved the best results between the other ML methods.

Quantitative MR Analysis of Changes in the Radius Bone Marrow in Osteoporosis.

This pilot study aimed to explore the feasibility of scanning the human distal radius bone marrow in vivo to detect osteoporosis-related changes using magnetic resonance and evaluate whether the radius may serve as an accessible probing site for osteoporosis. This may lead in the future to the use of affordable means such as low-field MRI scanners for the monitoring of disease progression. A clinical trial was performed using a 3T MR scanner, including 26 women assigned into three study groups: healthy-premenopausal (n = 7; mean age 48.6 ± 3.5 years), healthy-postmenopausal (n = 10; mean age 54.5 ± 5.6 years), and osteoporotic-postmenopausal (n = 9; mean age 61.3 ± 5.6 years). Marrow fat composition was evaluated using T2 maps, a two-compartment model of T1, and a Dixon pulse sequence. The osteoporotic group exhibited higher fat content than the other two groups and lower T2 values than the healthy-premenopausal group. Osteoporosis-related changes in the composition of the distal radius bone marrow may be detected in vivo using MRI protocols. The scanning protocols chosen here can later be repeated using low-field MRI scanners, thus offering the potential for early detection and treatment monitoring, using an accessible, affordable means that may be applied in small clinics. This trial is registered with MOH_2018-05-23_002247, NCT03742362.

MRI ankle in juvenile idiopathic arthritis and its comparison with clinical disease activity scores

Objectives: Juvenile idiopathic arthritis (JIA) is a common cause of morbidity and consequent disability among youth up to 16 years of age. Our study aims to image the ankle joints of JIA patients and correlate the findings with the clinical disease activity scores. Juvenile Arthritis Disease Activity Score (JADAS-27) is used by pediatricians to assess disease activity in JIA patients. There are four factors that determine this score – Global assessment of disease activity by the physician as well as patient/parent, joint count with active disease, and erythrocyte sedimentation rate (ESR). However, these clinical scores are dependent on the clinician’s experience and observation and, therefore, subjective. Material and Methods: Thirty patients of either sex with a clinical diagnosis of JIA as per the International League of Association for Rheumatology definition with clinically involved ankle joints were included in the study. Chronic arthritis due to other causes, such as infection, trauma, and so on, was excluded. All clinically diagnosed cases of JIA were subjected to magnetic resonance imaging (MRI) evaluation on Siemens Skyra 3 Tesla High-Resolution MR system using a dedicated coil for the ankle joint. Six sub-joints for each patient are evaluated, namely - The tibiotalar joint, subtalar joint, calcaneocuboid joint, calcaneonavicular joint, naviculocuneiform joint, and tarsometatarsal joint. Image analysis and scoring shall be done for each patient at each joint as per the Juvenile Arthritis MRI SCORE, consisting of the following parameters-synovial hypertrophy score, cartilage lesion score, bone erosion score, and bone marrow change score. Each of these scores is calculated individually based on the percentage of involved bone volume. All individual scores were summed to get the total MRI Score. The data collected were then statistically analyzed. Results: A positive correlation was sought between the JADAS-27 score and the total MRI score with the P-value being 0.03. A positive correlation was also found between the total MRI score and the ESR value of the patient (P - 0.02). Conclusion: MRI findings can be a potential marker of disease activity in JIA patients and these findings could also predict the prognosis accurately in these patients. The findings are objective and comparable to the aforementioned clinical scores.

Understanding the Impact of HIV-Associated Bone Marrow Alterations on Erythropoiesis

Human Immunodeficiency Virus (HIV) infection presents a multifaceted challenge, extending beyond its primary impact on the immune system to affect various organ systems. Among these, the bone marrow, the primary site for hematopoiesis, undergoes substantial alterations during HIV infection, profoundly influencing erythropoiesis—the process of red blood cell production. Anemia, a prevalent hematologic complication in HIV-infected individuals, often serves as a marker of disease progression and impacts overall health outcomes. This paper aims to delve into the intricate relationship between HIV-associated bone marrow alterations and their consequential effects on erythropoiesis. The mechanisms underlying bone marrow changes in HIV infection, including direct viral effects, dysregulation of cytokine networks, and inflammatory processes, significantly disrupt the delicate balance necessary for efficient erythropoiesis. The impact of these alterations on erythropoiesis manifests through ineffective red blood cell production, decreased erythropoietin responsiveness, and shortened red blood cell lifespan. Chronic inflammation further complicates erythropoietic processes, contributing to the development and perpetuation of anemia in HIV-infected individuals. Therapeutic interventions encompass a multifaceted approach, including antiretroviral therapy (ART) to control viral replication, erythropoiesis-stimulating agents, and adjunctive nutritional support to manage anemia. However, emerging research targeting bone marrow microenvironmental factors and novel agents stimulating erythropoiesis offer promising avenues for future therapeutic development. Keywords: HIV, bone marrow, erythropoiesis, erythropoietin, antiretroviral therapy

Immunomodulatory Nanoparticles for Modulating Arthritis Flares.

Disease-modifying drugs have improved the treatment for autoimmune joint disorders, such as rheumatoid arthritis, but inflammatory flares are a common experience. This work reports the development and application of flare-modulating poly(lactic-co-glycolic acid)-poly(ethylene glycol)-maleimide (PLGA-PEG-MAL)-based nanoparticles conjugated with joint-relevant peptide antigens, aggrecan70-84 and type 2 bovine collagen256-270. Peptide-conjugated PLGA-PEG-MAL nanoparticles encapsulated calcitriol, which acted as an immunoregulatory agent, and were termed calcitriol-loaded nanoparticles (CLNP). CLNP had a ∼200 nm hydrodynamic diameter with a low polydispersity index. In vitro, CLNP induced phenotypic changes in bone marrow derived dendritic cells (DC), reducing the expression of costimulatory and major histocompatibility complex class II molecules, and proinflammatory cytokines. Bulk RNA sequencing of DC showed that CLNP enhanced expression of Ctla4, a gene associated with downregulation of immune responses. In vivo, CLNP accumulated in the proximal lymph nodes after intramuscular injection. Administration of CLNP was not associated with changes in peripheral blood cell numbers or cytokine levels. In the collagen-induced arthritis and SKG mouse models of autoimmune joint disorders, CLNP reduced clinical scores, prevented bone erosion, and preserved cartilage proteoglycan, as assessed by high-resolution microcomputed tomography and histomorphometry analysis. The disease protective effects were associated with increased CTLA-4 expression in joint-localized DC and CD4+ T cells but without generalized suppression of T cell-dependent immune response. The results support the potential of CLNP as modulators of disease flares in autoimmune arthropathies.