Bone Marrow Changes Research Articles

18F-FDG PET-defined therapy response to predict acute hematologic toxicity for anal cancer patients treated with chemoradiation.

775 Background: Hematologic toxicities (HT) induced during chemoradiotherapy (CRT) for anal cancer can lead to increased infection rates, bleeding, asthenia, and unplanned breaks compromising treatment efficacy. We hypothesize that HT in anal cancer patients treated with CRT correlate with change in active bone marrow (ABM) characterized by pre- and post-CRT 18F-FDG PET/CT (PET). Methods: Twenty-eight locally advanced anal cancer patients treated with definitive CRT from 2011-2016 were identified. PET scans were obtained 0-2 weeks pre- and 6-8 weeks post-CRT. HT was evaluated by weekly white blood cell count, absolute neutrophil count (ANC), hemoglobin (Hg) and platelet nadirs. Total bone marrow (TBM) was defined on CT images, and segmented into three subregions: lumbosacral (LS), left and right iliac pelvis. PET images were normalized to bone outside of the TBM uptakes. ABM was characterized in all PET images as the volume having standard uptake value SUV > 40% of SUVmax in the TBM. Image variables (global, subregional SUVmean, SUVmax, ABMs) of pre- and post-CRT and their differential changes were evaluated as predictors of HT. Locoregional radiomics features were calculated using a 3D kernel-based approach. HT prediction was modeled by logistic regression with the Lasso algorithm with 10-fold cross-validation. HT endpoints were defined as change between baseline blood nadir and the lowest nadir values during and up to 2 weeks after CRT. Results: The lasso regression identified 5 predictors of HT (pre-SUVmax, post-LS-ABM, LS-ABM change, homogeneity texture change, and variance). Ratios of LS-ABMs to TBM were reduced from 18.9% (pre-CRT) to 16.3% (post-CRT). This reduction of LS-ABM significantly correlated with acute HT measured by ANC (p < 0.001) and Hg (p < 0.001) nadirs. Conclusions: PET-derived active BM changes between pre- and post-CRT significantly associated with HT in anal cancer patients undergoing definitive CRT. LS-ABM is a robust surrogate for evaluation of HT and can be used to develop BM-sparing radiotherapy for reduction of potential HT.

Magnetic Resonance Imaging correlates of benign and malignant alterations of the spinal bone marrow.

Background and aim of the work: Bone marrow (BM) abnormalities in the spine are a common, sometimes unexpected, finding on Magnetic Resonance Imaging (MRI), which is the most sensitive imaging modality to evaluate the marrow, and their interpretation can be difficult for the unexperienced radiologist. In this review, the MRI appearance of normal age-related BM changes, as well as the imaging features of benign and malignant diseases, are presented. Discussion: A large variety of BM signal alterations has been identified and described, including normal variants, BM reconversion, degenerative changes, infections, spondyloarthritis and osteonecrosis, trauma, neoplastic lesions (both primary or metastatic), post-radiation and chemotherapy sequelae. Conclusions: Knowledge of normal age-related BM appearance, normal variants and patterns of involvement in focal and diffuse bone diseases is essential, together with clinical and laboratory data, to narrow the list of the possible differential diagnoses. The radiologist should be familiar with these signal changes, as they can sometimes be discovered incidentally. In this context, it is equally important not to attribute pathological significance to benign alterations and to promptly detect signs of malignant diseases. (www.actabiomedica.it)

Histopathological changes of bone marrow in patients with autosomal recessive osteopetrosis and mutation in TCIRG1 gene

Osteopetrosis is a group of rare hereditary diseases, the general structural manifestation of which is the excessive volume of bone tissue due to violation of osteoclastic resorption. The only way to treat this group of patients so far remains transplantation of hematopoietic stem cells, but the degree of its effectiveness largely depends on the severity of morphological changes in the hematopoietic microenvironment in the bone marrow. In this regard, a comprehensive clinical and morphological analysis, in conjunction with the results of transplantation can help in determining the prognosis of the disease depending on the genetic type of osteopetrosis. The material for the studies were biopsies and smears of bone marrow of patients with osteopetrosis, who were received at the R. Gorbacheva Memorial Research Institute for Pediatric Oncology, Hematology and Transplantation from the republics of Chuvashia and Mari El for carrying out transplantation of hematopoietic stem cells. The histological preparations were stained with hematoxylin and eosin, azur by Romanovsky and by Van Gieson. Bone marrow smears were stained by Romanovsky-Giemsa. The presence of the mutation c.807 + 5G>A in the gene TCIRG1 in patients with autosomal recessive osteopetrosis causes a complete loss of osteoclastic resorption, which is accompanied by pronounced early structural changes in the hematopoietic microenvironment already at the time of diagnosis. This is manifested by an excessive amount of lamellar bone at the same time as the almost complete obliteration of the medullar lacunae, as well as fibrosis of the bone marrow stroma. A common morphological phenomenon among this group of patients is the presence in the bone marrow of an excessive number of osteoclast differentiation cells without the formation of resorption lacunae. This causes a complete suppression of hemopoiesis, which clinically manifests cytopenia and the formation of foci of extramedullary hematopoiesis. Such pronounced structural changes in the hematopoietic microenvironment result in a high risk of primary graft failure during after transplantation of bone marrow hematopoietic stem cells, the effectiveness of which decreases as the child's age increases. Early development of pronounced structural changes in the hematopoietic microenvironment in patients with TCIRG1-mediated osteopetrosis determines the need for diagnosis and transplantation as soon as possible after birth.

Antibiotic treatment In patients with chronic low back pain and Modic changes (the AIM study): study protocol for a randomised controlled trial

BackgroundA previous randomised controlled trial (RCT) of patients with chronic low back pain (LBP) and vertebral bone marrow (Modic) changes (MCs) on magnetic resonance imaging (MRI), reported that a 3-month, high-dose course of antibiotics had a better effect than placebo at 12 months’ follow-up. The present study examines the effects of antibiotic treatment in chronic LBP patients with MCs at the level of a lumbar disc herniation, similar to the previous study. It also aims to assess the cost-effectiveness of the treatment, refine the MRI assessment of MCs, and further evaluate the impact of the treatment and the pathogenesis of MCs by studying genetic variability and the gene and protein expression of inflammatory biomarkers.Methods/designA double-blinded RCT is conducted at six hospitals in Norway, comparing orally administered amoxicillin 750 mg, or placebo three times a day, over a period of 100 days in patients with chronic LBP and type I or II MCs at the level of a MRI-confirmed lumbar disc herniation within the preceding 2 years. The inclusion will be stopped when at least 80 patients are included in each of the two MC type groups. In each MC type group, the study is designed to detect (β = 0.1, α = 0.05) a mean difference of 4 (standard deviation 5) in the Roland Morris Disability Questionnaire score between the two treatment groups (amoxicillin or placebo) at 1-year follow-up. The study includes cost-effectiveness measures. Blood samples are assessed for security measures and for possible inflammatory mediators and biomarkers at different time points. MCs are evaluated on MRI at baseline and after 12 months. A blinded intention-to-treat analysis of treatment effects will be performed in the total sample and in each MC type group.DiscussionTo ensure the appropriate use of antibiotic treatment, its effect in chronic LBP patients with MCs should be re-assessed. This study will investigate the effects and cost-effectiveness of amoxicillin in patients with chronic LBP and MCs at the level of a disc herniation. The study may also help to refine imaging and characterise the biomarkers of MCs.Trial registrationClinicalTrials.gov, ID: NCT02323412. Registered on 21 November 2014.

Quantitative analysis of bone marrow in pancytopenic dogs

The pancytopenia can be associated with intra and extra medullary disorders. When the etiology is not obvious, the examination of bone marrow is necessary. The study aims to report and discuss quantitative amendments in bone marrow and their causes in dogs with pancytopenia. Bone marrow aspirate was obtained from 65 dogs with pancytopenia over a period of 13 consecutive months for preparation of smears stained by Giemsa and observed in light microscopy. Five hundred cells differential count was held; and assessed myeloid:erythroid ratio, cellularity, megakaryocytes and direct parasitological examination. The data were evaluated by the Chi-square statistical test. Blood tests of 3120 canines with several clinical changes were analyzed to identify pancytopenia, which accounted for 167 (5.4%) dogs. Interpretation of quantitative characteristics was carried out from the bone marrow smear in 65 pancytopenic dogs and the etiology was established in 40 (61.5%) of these, which included infection by E. canis and L. chagasi, idiopathic aplastic anemia, chronic renal failure and co-infections. In 17 (26.2%) animals were not observed medullary changes. The most bone marrow change was observed myeloid and erythroid hypoplasia in 17 (26.2%) dogs, followed by myeloid and erythroid hyperplasia (24.6%). The myelogram association to the blood cell count allowed the identification of medullary findings and its participation on the occurrence of pancytopenia cases. The number of cases resulting from infectious diseases was 38 (58.5%) in canine assessed: significant number due to its endemic characteristic of the study region.

A relative increase in circulating platelets following chemoradiation predicts for poor survival of patients with glioblastoma.

BackgroundThrombocytosis is triggered by and promotes tumor growth. The relationship between the change in circulating platelets after chemoradiation therapy (CRT) or adjuvant temozolomide (TMZ) and survival in glioblastoma remains unclear. We hypothesized that an increase in platelets after these treatments would be predictive of a shorter survival.MethodsWe retrospectively reviewed data on 122 patients with newly diagnosed, pathologically proven glioblastoma who had been treated with surgery, followed by CRT and adjuvant TMZ, from 2007 to 2016. The association between the changes in blood count levels and survival was analyzed by the log-rank test. To adjust for confounding, we performed a multivariate analysis using known prognostic co-variates.ResultsPatients were dichotomized on the basis of the relative change in platelets after CRT from the baseline: ≤30% increase, low (n = 101) vs >30% increase, high (n = 12). The median survival for high vs. low platelets were 11 vs 28 months (p = 0.0062). No significant survival differences were observed on the basis of platelet changes during adjuvant TMZ. Similarly, changes in lymphocyte counts were not significantly prognostic. On multivariate analysis, MGMT, performance status, and an increase in platelets after CRT were significantly associated with survival (HR for platelets, 4.5; 95% confidence interval, 1.6-12.6).ConclusionsIncreased platelet counts after CRT are predictive of poor survival in glioblastoma. The effect is platelet specific and does not reflect bone marrow changes, as lymphocyte changes were not significantly prognostic. These results suggest an interaction between platelets and tumor aggressiveness. Thus, platelets serve as a novel, minimally invasive liquid biopsy for predicting outcome.

Calcitonin gene-related peptide-transfected bone marrow mesenchymal stem cells combined with autologous bone grafting to treat osteonecrosis of the femoral head in rabbit model

Objective To investigate the histopathological changes of calcitonin peptide-transfected bone marrow mesenchymal stem cells (BMSCs) combined with bone transplantation in the treatment of osteonecrosis of the femoral head (ONFH) in rabbit model. Methods The osteonecrosis models on one side femoral head of rabbits were established by liquid nitrogen. Forty-eight rabbit ONFH models were randomly divided into 3 groups. In human calcitonin gene-related peptide α (hCGRPα)-transfected BMSCs group (A), the BMSCs transfected with hCGRPα in combination with autologous bone graft were implanted into the femoral head. In empty plasmid group (B), the BMSCs transfected with empty plasmid (only pLNCX2 plasmid) and autologous bone graft were implanted. In irrelated sequence group (C), BMSCs transfected with irrelated gene [only pLNCX2-green fluorescent protein (GFP)] and autologous bone graft were implanted. Animals were sacrificed at 3rd and 6th month respectively to observe the histopathological changes in the femoral heads of rabbits. Results At 3rd month, the bone trabecular area fraction respectively was (40.89±1.12)%, (36.12±1.17)%, (36.33±1.53)% and (42.11±1.91)% in groups A, B and C and normal femoral head. The percentage of empty osteocyte lacunae respectively was (11.34±1.58)%, (16.33±1.45)%, (17.21±1.23)% and (10.47±1.41)% in groups A, B and C and normal femoral head. In group A, there were proliferation and growth of a large number of osteocytes, more mature bone trabeculae and higher area fraction, less empty osteocyte lacunae, and stronger biomechanical strength in the femoral head, which were nearly close to those in the normal control group and obviously superior to those in groups B and C. In groups B and C, there were thin and irregular bone trabeculae, more empty osteocyte lacunae, lower area fraction and imperfect bone repair. At 6th month, the bone trabeculae were mature, densification and satiation, and neatly arranged rules were seen in the femoral head of group A. The area fraction of bone trabeculae and the number of empty bone lacunae in group A were superior to those in groups B and C. Conclusion The implantation of hCGRPα-transfected BMSCs combined with autologous bone graft into the femoral head of ONFH animal models can significantly promote cells proliferation, accelerate osteogenesis, enhance bone tissue repair, and obtain good effect in the treatment of ONFH. Key words: Calcitonin gene related peptide; Bone marrow mesenchymal stem cells; Osteonecrosis of the femoral head necrosis; Model, animal

Contrast-enhanced MRI findings of the knee in healthy children; establishing normal values

ObjectivesTo define normative standards for the knee in healthy children using contrast-enhanced MRI, focusing on normal synovial membrane thickness. Secondly, presence of joint fluid and bone marrow oedema was evaluated.MethodsFor this study, children without disorders potentially resulting in (accompanying) arthritis were included. Patients underwent clinical assessments, followed by contrast-enhanced MRI. MRI features were evaluated in consensus using the Juvenile Arthritis MRI Scoring (JAMRIS) system. Additionally, the presence of joint fluid was evaluated. No cartilage lesions or bone abnormalities were observed.ResultsWe included 57 healthy children. The overall mean thickness of the normal synovial membrane was 0.4 mm (min–max; 0.0–1.8mm). The synovium was thickest around the cruciate ligaments and retropatellar and suprapatellar regions. The mean overall diameter of the largest pocket of joint fluid was 2.8 mm (min–max; 0.9–8.0mm). Bone marrow changes were observed in three children (all in the apex patellae).ConclusionsThe normal synovial membrane was maximally 1.8 mm thick, indicating that the JAMRIS cut-off value of 2 mm can be considered a valid measure for evaluating synovial hypertrophy. Some joint fluid and bone marrow changes suggestive of bone marrow oedema in the apex patellae can be seen in healthy children.Key Points• Knowledge on the normal synovial appearance using contrast-enhanced MR is lacking.• In healthy children, normal synovial membrane is maximally 1.8 mm thick.• Normal synovium is thickest around the cruciate ligaments, retropatellar and suprapatellar.• Bone marrow oedema in the apex patellae is seen in healthy children.

Bone Marrow Findings Secondary to Antineoplastic Compounds: Hematopoietic, Bone, and Cytokine Cross Talk.

New medullary bone formation has been observed in rats administered a variety of antineoplastic compounds. Similar effects reported in rats administered granulocyte colony-stimulating factor (G-CSF) were attributed to exaggerated pharmacology of G-CSF as a cytokine and growth factor, resulting in stromal proliferation in addition to the intended hematopoietic effects. Similar phenomena of marrow stromal change are reported among other species in association with various growth factors. Case study summaries of test item-related histopathologic changes in bone marrow, reflecting trabecular and/or endosteal new bone formation, are presented. In each of these cases, it was concluded that the new medullary bone and stromal proliferation did not reflect a primary target-related toxicity; rather, the mesenchymal changes were attributed to nonspecific, secondary effects of cytokines elaborated in response to primary cytotoxic effects on hematopoietic cells with subsequent impact on circulating blood cells. The common features associated with marrow stromal changes in the case studies, as well as with a variety of pharmacologic compounds across several species described in the literature, are hematologic effects and/or changes in growth factor levels and cytokine expression.

Posttherapeutic changes in bone marrow

The bone marrow basically consists of red blood-forming bone marrow and yellow fat. In the skeleton, there is an age-dependent distribution of these two parts. In the context of medical interventions or therapies, bone marrow changes can occur, whereby the normal bone marrow can basically be replaced by fat, edema, or fibrosis/sclerosis. Here, specific signal intensities and patterns are shown in imaging. After irradiation therapies, edematous changes, hemorrhages, and osteoradionecroses are observed. Likewise, insufficiency fractures, impairment of the growth gaps, or the development of tumors is possible. In patients on dialysis, deposit of protein in the bone marrow is possible in the case of the so-called amyloidosis osteoarthropathy. Postoperative bone marrow edema, insufficiency fractures, or osteonecrosis can be observed after arthroscopy. Changes in the distribution of fat markers and blood-forming bone marrow can be observed after stem cell transplants. In the therapy with cortisone, insufficiency fractures and osteonecroses are possible. Depending on their effect on the hematopoietic system, chemotherapyies can first lead to edematous changes and then to fatty bone marrow, which is reversible after therapy. Angiogenesis inhibitors in combination with other chemotherapeutic agents often lead to mixed images of stimulated and fatty bone marrow.

Inflammatory response of disc cells against Propionibacterium acnes depends on the presence of lumbar Modic changes.

Intervertebral disc with Propionibacterium acnes (P. acnes) is suggested to be an etiology of Modic type I changes in the adjacent bone marrow. However it is unknown if disc cells can respond to P. acnes and if bone marrow cells respond to bacterial and disc metabolites draining from infected discs. Human disc cells (n=10) were co-cultured with 10- and 100-fold excess of P. acnes over disc cells for 3h and 24h. Lipopolysaccharide was used as positive control. Expression of IL1, IL6, IL8, and CCL2 by disc cells was quantified by quantitative PCR. Lipase activity was measured in culture supernatants (n=6). Human vertebral bone marrow mononuclear cells (BMNCs) (n=2) were cultured in conditioned media from disc cell/P. acnes co-cultures and expression of IL1, IL6, IL8, and CCL2 was measured after 24h. All disc cells responded to lipopolysaccharide but only 6/10 responded to P. acnes with increased cytokine expression. Cytokine increase was time- but not P. acnes concentration-dependent. Disc cell responsiveness was associated with the presence of lumbar Modic changes in the donor. Lipase activity was increased independent of disc cell responsiveness. BMNCs responded with inflammatory activity only when cultured in supernatants from responsive disc cell lines. Disc cell responsiveness to P. acnes associates with the presence of lumbar Modic changes. Furthermore, bone marrow cells had an inflammatory response to the cocktail of disc cytokines and P. acnes metabolites. These data indicate that low virulent P. acnes infection of the disc is a potential exacerbating factor to Modic changes.

Neural tube defects and folic acid in Japan: Prologue introduction ‐ Understanding of the current status of Japan and the proposal from Japanese Teratology Society

Neural tube defects and folic acid in Japan: Prologue introduction ‐ Understanding of the current status of Japan and the proposal from Japanese Teratology Society

Apparent diffusion coefficient maps in the assessment of surgical patients with lumbar spine degeneration.

PurposeTo assess the utility of apparent diffusion coefficient (ADC) maps for the assessment of patients with advanced degenerative lumbar spine disease and describe characteristic features of ADC maps in various degenerative lumbar spinal conditions.MethodsT1-weighted, T2-weighted and diffusion weighted (DWI) MR images of 100 consecutive patients admitted to the spinal surgery service were assessed. ADC maps were generated from DWI images using Osyrix software. The ADC values and characteristic ADC maps were assessed in the regions of interest over the different pathological entities of the lumbar spine.ResultsThe study included 452 lumbar vertebral segments available for analysis of ADCs. Characteristic ADC map features were identified for protrusion, extrusion and sequester types of lumbar disk herniations, spondylolisthesis, reactive Modic endplate changes, Pfirrmann grades of IVD degeneration, and compromised spinal nerves. Compromised nerve roots had significantly higher mean ADC values than adjacent (p < 0.001), contralateral (p < 0.001) or adjacent contralateral (p < 0.001) nerve roots. Compared to the normal bone marrow, Modic I changes showed higher ADC values (p = 0.01) and Modic 2 changes showed lower ADC values (p = 0.02) respectively. ADC values correlated with the Pfirrmann grading, however differed from herniated and non-herniated disks of the matched Pfirrmann 3 and 4 grades.ConclusionQuantitative and qualitative evaluation of ADC mapping may provide additional useful information regarding the fluid dynamics of the degenerated spine and may complement standard MRI imaging protocol for the comprehensive assessment of surgical patients with lumbar spine pathology. ADC maps were advantageous in differentiating reactive bone marrow changes, and more precise assessment of the disk degeneration state. ADC mapping of compressed nerve roots showed promise but requires further investigation on a larger cohort of patients.

Whole body proton irradiation causes acute damage to bone marrow hematopoietic progenitor and stem cells in mice

Purpose: Exposure to proton irradiation during missions in deep space can lead to bone marrow injury. The acute effects of proton irradiation on hematopoietic stem and progenitor cells remain undefined and thus were investigated.Materials and methods: We exposed male C57BL/6 mice to 0.5 and 1.0 Gy proton total body irradiation (proton-TBI, 150 MeV) and examined changes in peripheral blood cells and bone marrow (BM) progenitors and LSK cells 2 weeks after exposure.Results: 1.0 Gy proton-TBI significantly reduced the numbers of peripheral blood cells compared to 0.5 Gy proton-TBI and unirradiated animals, while the numbers of peripheral blood cell counts were comparable between 0.5 Gy proton-TBI and unirradiated mice. The frequencies and numbers of LSK cells and CMPs in BM of 0.5 and 1.0 Gy irradiated mice were decreased in comparison to those of normal controls. LSK cells and CMPs and their progeny exhibited a radiation-induced impairment in clonogenic function. Exposure to 1.0 Gy increased cellular apoptosis but not the production of reactive oxygen species (ROS) in CMPs two weeks after irradiation. LSK cells from irradiated mice exhibited an increase in ROS production and apoptosis.Conclusion: Exposure to proton-TBI can induce acute damage to BM progenitors and LSK cells.

Effect of Methotrexate and Omega-3 Combination on Cytogenetic Changes of Bone Marrow and Some Enzymatic Antioxidants: An Experimental Study

Effect of Methotrexate and Omega-3 Combination on Cytogenetic Changes of Bone Marrow and Some Enzymatic Antioxidants: An Experimental Study

Effect of Methotrexate and Omega-3 Combination on Cytogenetic Changes of Bone Marrow and Some Enzymatic Antioxidants: An Experimental Study

Effect of Methotrexate and Omega-3 Combination on Cytogenetic Changes of Bone Marrow and Some Enzymatic Antioxidants: An Experimental Study

5-FU-Injured Bone Marrow Stromal Cells Initiate Stress-induced Premature Senescence of Hematopoietic Cells

To investigate the damage effect of 5-fluorouracil(5-FU) with tumor inhibition concentration on human bone marrow mesenchymal stem cells (hBMSC) and influence of its effect on the hematopoietic cells. The Cell Counting Kit-8 was used for determining the sensitivity of breast cancer cell line MCF-7, colon cancer cell line HCT-116 and HS-5 derived from human bone marrow stronal cell line to the different doses of 5-fluorouracil in vitro. After HS-5 was treated with 5-fluorouracil, crystal violet staining assay was used to count the number of colony forming unit-fibroblast, the distribution of cell cycle was analyzed by flow cytometry (FCM), apoptosis was assessed by Annexin V/PI double-stained method and Hoechest staining; DCFH-DA staining was used to analyse the level of reactive oxygen species (ROS), ELISA and immuofluorescence were used to detect cytokines KL, GM-CSF, RANTS and SDF. The hUCB-MNC was counted by trypan blue staining after co-culture with HS-5, FCM was used to detect the cell cycle distribution, ROS level and the ratio of CD34+ cells. The levels of glutathione peroxidase (GSH-Px) and total superoxide dismutase(T-SOD) were measured by enzymatic assay. The senescence associated-β-galactosidase (SA-β-Gal) staining was used to detect the senescent hUCB-MNC. 5-Fluorouracil of 12.5 µg/ml-100 µg/ml inhibited the proliferation of MCF-7, HCT-116 and HS-5 cells in dose-dependent and time-dependent manner, among them HS-5 was more sensitive to 5- fluorouracil. After treatment with 5-fluorouracil, the HS-5 cell cycle was blocked. The apoptosis rate and the intracellular ROS level of HS-5 significantly increased. Also HS-5-secreted hematopoietic growth factors decreased and inflammatory chemokines increased. After co-cultured with 5-fluorouracil-treated HS-5, the number of hUCB-MNC and the ratio of CD34+ cells were decreased. hUCB-MNC cell cycle blocked in G1 phase. The antioxidant capacity also decreased and the intracellular ROS level increased significantly. The senescent hUCB-MNC increased. 5-Fluorouracil can result in oxidative damage of bone marrow stromal cells and change of function secreting bioactivators, thus induce oxidative stress in hematopoietic cells to initiate stress-induced premature senescence (SIPS).

Interferon \u03b3 induced compositional changes in human bone marrow derived mesenchymal stem/stromal cells

BackgroundMesenchymal stem/stromal cells (MSC) display a range of immunoregulatory properties which can be enhanced by the exposure to cytokines such interferon γ (IFN-γ). However the compositional changes associated with the ‘licensing’ of these cells have not been clearly defined. The present study was undertaken to provide a detailed comparative proteomic analysis of the compositional changes that occur in human bone marrow derived MSC following 20 h treatment with IFN-γ.Methods2D LC MSMS analysis of control and IFN-γ treated cells from 5 different healthy donors provided confident identification of more than 8400 proteins.ResultsIn total 210 proteins were shown to be significantly altered in their expression levels (≥|2SD|) following IFN-γ treatment. The changes for several of these proteins were confirmed by flow cytometry. STRING analysis determined that approximately 30% of the altered proteins physically interacted in described interferon mediated processes. Comparison of the list of proteins that were identified as changed in the proteomic analysis with data for the same proteins in the Interferome DB indicated that ~35% of these proteins have not been reported to be IFN-γ responsive in a range of cell types.ConclusionsThis data provides an in depth analysis of the proteome of basal and IFN-γ treated human mesenchymal stem cells and it identifies a number of novel proteins that may contribute to the immunoregulatory capacity if IFN-γ licensed cells.

Effect of Modic Changes in Cervical Degenerative Disease.

ObjectiveModic changes are signal intensity changes in adjacent vertebral bone marrow on magnetic resonance imaging. Few studies have investigated these changes with regard to the cervical spine. In this study, we investigated the associations between cervical degenerative disease and Modic changes.MethodsWe conducted a retrospective collection of radiological data in patients with neck pain at Pusan National University Yangsan Hospital from January 2010 to December 2014. A total of 169 patients were included in this study. Disc herniation grade, disc space height and global cervical lordosis (C2–C7 Cobb angle) were measured and analyzed. If Modic changes were present, we recorded the Modic change type based on the literature, vertebral level, age, sex, and surgical requirement.ResultsSixty-six patients exhibited Modic changes in the cervical spine. Out of these 66 patients, Modic change type II (56 patients, 84.8%) and C5–6 vertebral level (23 patients, 34.8%) were the most predominant categories. Patients with Modic change showed worse outcomes in regard to disc herniation grade, disc space height and global cervical lordosis than patients without (p<0.01). Among 169 patients, 18 patients had undergone anterior cervical discectomy with fusion (ACDF). Patients with Modic changes (10 of 66 patients, 15.1%) had a greater probability of undergoing ACDF than those without (8 of 103 patients, 7.8%; p<0.01).ConclusionModic changes refer cervical degenerative changes, and incidence of ACDF is higher when the Modic changes are occurred.

Magnetic Resonance Imaging (MRI) of the Knee as an Outcome Measure in Juvenile Idiopathic Arthritis: An OMERACT Reliability Study on MRI Scales.

There is increasing evidence that early therapeutic intervention improves longterm joint outcome in juvenile idiopathic arthritis (JIA). Given the existence of highly effective treatments, there is an urgent need for reliable and accurate measures of disease activity and joint damage in JIA. Our objective was to assess the reliability of 2 magnetic resonance imaging (MRI) scoring methods: the Juvenile Arthritis MRI Scoring (JAMRIS) system and the International Prophylaxis Study Group (IPSG) consensus score, for evaluating disease status of the knee in patients with JIA. Four international readers independently scored an MRI dataset of 25 JIA patients with clinical knee involvement. Synovial thickening, joint effusion, bone marrow changes, cartilage lesions, bone erosions, and subchondral cysts were scored using the JAMRIS and IPSG systems. Further, synovial enhancement, infrapatellar fat pad heterogeneity, tendinopathy, and enthesopathy were scored. Interreader reliability was analyzed by using the generalized κ, ICC, and the smallest detectable difference (SDD). ICC regarding interreader reliability ranged from 0.33 (95% CI 0.12-0.52, SDD = 0.29) for enthesopathy up to 0.95 (95% CI 0.92-0.97, SDD = 3.19) for synovial thickening. Good interreader reliability was found concerning joint effusion (ICC 0.93, 95% CI 0.89-0.95, SDD = 0.51), synovial enhancement (ICC 0.90, 95% CI 0.85-0.94, SDD = 9.85), and bone marrow changes (ICC 0.87, 95% CI 0.80-0.92, SDD = 10.94). Moderate to substantial reliability was found concerning cartilage lesions and bone erosions (ICC 0.55-0.72, SDD 1.41-13.65). The preliminary results are promising for most of the scored JAMRIS and IPSG items. However, further refinement of the scoring system is warranted for unsatisfactorily reliable items such as bone erosions, cartilage lesions, and enthesopathy.