Bone Marrow Changes Research Articles

Diagnostic Problems in Chronic Basophilic Leukemia

Chronic basophilic leukemia (CBL) is an extremely rare type of leukemia. A literature review revealed six cases reported as primary CBL and five patients with secondary CBL. Patients with primary CBL may present with symptoms not related to leukemia. Dysplastic changes in peripheral blood and bone marrow were described and demonstrated in cases of primary and secondary CBL. The literature review also revealed that differential counts made by automated blood cell counters may not characterize cells as basophils in patients with primary and secondary CBL and may mislead physicians in making a differential diagnosis. For these reasons, laboratory studies for the diagnosis of CBL are required, including metachromatic staining by toluidine blue and antigen expressions by flow cytometric analysis, to detect the nature of the neoplastic cells as basophils for a reliable diagnosis of CBL. The literature review failed to reveal specific cytogenetic findings in patients with primary and secondary types of CBL.

Changes in Pelvic Active Bone Marrow seen on FDG-PET in Patients Receiving Concurrent Chemoradiation for Anal Cancer

Radical concurrent chemoradiation (CRT) for locally advanced anal cancer is associated with suppression of active bone marrow. We seek to determine the degree of suppression seen in FDG-PET imaging attributable to chemotherapy and attributable to chemoradiation. Anal cancer patients undergoing CRT had FDG PET scans prior to treatment (baseline scan) and at radiotherapy fraction 8-10 (wk2 scan) as part of the ART Trial (Anal squamous cell carcinoma: Investigation of functional imaging during CRT NCT02145416). RT was delivered in 28 fractions; 53.2/50.4 Gy to tumor and involved nodes, 40 Gy to elective nodes. Chemotherapy consisted of 12 mg/m2 Mitomycin D1 and 825 mg/m2 Capecitabine D1-D28 radiotherapy days only. PET scans were taken on GE Discovery scanner after 60 min (75 min on average) FDG uptake time. Whole bone was used to define bone marrow. Average SUV values were extracted from static scans for irradiated whole pelvic bone marrow (PBM), PBM substructures (iliac BM, lower pelvic BM, and lumbosacral BM) and non-irradiated thoracic spine (T9-11) using a treatment planning system. Median SUV in whole PBM was compared using Wilcoxon signed-rank test. Of the 29 patients recruited to ART, 12 had PET scans at both time points. Of these, two patients received 61.6 Gy in 28 and one 41.4 Gy in 23. All other patients received standard radiotherapy of 50.4 Gy (3 patients total) or 53.2 Gy (6 patients total). RT plan PBM V10 exceeded 60% for all patients and V20 exceeded 47%, equating to >2.9 Gy and 5.7 Gy, respectively, at the time of wk2 scan. A summary of SUV values is seen in the Table below.Abstract SU_4_2038; Table 1PBMIliac BMLower Pelvis BMLumbosacral BMT9-11Baseline Median1.131.171.001.331.66 Max1.631.691.402.072.70 Min0.830.900.730.901.28Wk2 Median0.991.090.851.161.67 Max1.231.331.091.432.37 Min0.740.740.640.790.45 Open table in a new tab There was a statistically significant reduction in the median SUV in the PBM from baseline to wk2 scan (median difference -0.20 (95% CI: -0.29, -0.04), p=0.006). A decrease was seen in all substructures with the largest decrease seen in lumbosacral (-0.22, -0.41, -0.07) and roughly equal reduction in iliac (-0.16, -0.31, 0.01) and lower pelvis (-0.16, -0.27, -0.01). A reduction was not observed in the non-irradiated thoracic spine (0.05, -0.25, 0.19)). The impact of concurrent chemoradiation on PBM is seen in reduced SUV values at wk2 compared to baseline. The effect of chemo only on SUV appears non-significant at wk2. Suppression of active bone marrow in CRT for anal cancer is therefore likely the combined toxicity of chemoradiation with chemotherapy in isolation relatively well tolerated at wk2 of treatment. Larger scale studies are required. The Oxford C REC ethically approved the trial. The trial was sponsored by the University of Oxford, funded by the CRUK & EPSRC Cancer Imaging Centre Oxford, and managed by the Oxford Clinical Trials and Research Unit. Oversight was provided by the Radiotherapy and Imaging Oversight Committee.

Cynomolgus monkeys (Macaca fascicularis) experimentally and naturally infected with hepatitis E virus: The bone marrow as a possible new viral target.

Hepatitis E virus (HEV) transmission through infected blood and blood products has already been described. However, little is known about the bone marrow (BM) as source of HEV infection. Our study aimed to investigate the presence of HEV antigen (Ag) and histological changes in BM of cynomolgus monkeys (Macaca fascicularis) experimentally and naturally infected with HEV. Four cynomolgus monkeys with acute, and two with chronic hepatitis E ─ after immunosuppressive therapy with tacrolimus ─ were compared with one colony-bred animal naturally infected. Both, natural and experimental infections were characterized by anti-HEV IgG seroconversion detected by ELISA, and viral RNA isolation confirmed by RT-qPCR and qualitative nested RT-PCR. BM biopsies were collected from all animals, submitted to histology and indirect immunofluorescence techniques and observed, respectively, by light and confocal microscopy. The HEV Ag-fluorescent-labeled cells were detected from BM biopsies obtained from three monkeys with acute and one with chronic hepatitis E, and also from the naturally infected monkey. In the experimentally infected animals with acute hepatitis, HEV Ag detection occurred at 160 days post-infection, even after viral clearance in serum, feces, and liver. Double-stranded RNA, a replicative marker, was detected in BM cells from both acute and chronically infected animals. Major histological findings included vacuolization in mononuclear and endosteal cells, an absence of organized inflammatory infiltrates, and also some fields suggesting displasic focal BM disease. These findings support the hypothesis of BM cells as secondary target sites of HEV persistence. Further experimental studies should be carried out to confirm the assumption of HEV transmission through BM transplantation.

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Utility of the claw sign in spine magnetic nuclear resonance with diffusion to differentiate Modic type I changes for degenerative disease versus infection.

In 1988, Modic and his colleagues described changes in the subchondral bone marrow of the vertebral plates in patients with degenerative disease or other pathologies, which were observed in the nuclear magnetic resonance (NMR) of the spine and were subdivided into three patterns of signal changes, called Modic type I, Modic type II and Modic type III. The main differential diagnosis of the Modic I changes of the vertebral plates due to degenerative disease in spine NMR, is infection in its early stages. In their study in 2014, Patel and collaborators, using a protocol and the concept of diffusion in spine MRI, were able to demonstrate that by means of the "claw sing", a degenerative disease with Modic type I changes, can be differentiated from an infection in early stages. In this series of cases, the algorithm used by Patel et al. was implemented. The clinical records of patients who consulted the emergency department for lumbar pain without clear etiology, between January 1, 2017 and December 31, 2017, were analyzed. Due to axial lumbar pain, subjects were hospitalized and studies were ordered, including contrasted MRI of the lumbosacral spine. Then, with laboratory tests and MRI findings of Modic type I changes, it was not possible to differentiate between degenerative disease vs. spondylodiscitis. Therefore, the algorithm used in the study by Patel and collaborators was applied. There were 13 patients identified with lumbar or dorsal pain over 3 months of evolution, with nonspecific symptoms; 5 patients (38.46%) reported arterial hypertension, 4 patients (30.77%) diabetes mellitus, and 4 patients (30.77%) chronic kidney disease stage V in management with hemodialysis, 3 patients (23.08%) presented immunosuppressive conditions and 3 patients (23.08%) had a history of spinal surgery with instrumentation. All the patients were hospitalized and a lumbosacral and thoracic spine simple MRI was performed with Modic type I changes to perform contrast-enhanced MRI with diffusion and ADC. From the 13 cases studied for low back pain, there were 7 patients (53.85%) with confirmed findings of Modic type I changes due to degenerative disease for presenting claw sign in spinal MRI diffusion and 6 patients (46.15%) Modic type changes I due to infection in the absence of a claw sign in the column MRI diffusion. Spinal column MRI with diffusion is useful to differentiate patients with type I changes due to degenerative disease with positive claw sign; of patients with type I changes due to infection with absent claw sign. In addition, in patients with compromised renal function, column MRI with diffusion without contrast could be a diagnostic alternative, since it does not require contrast media to confirm infection.

Effect of carcase decomposition on the inactivation of foot-and-mouth disease virus under northern Australian conditions.

The control of foot-and-mouth disease virus (FMDV) across northern Australia would likely result in animal carcases that will often be inaccessible for disposal. The aim of this preliminary study was to determine whether the natural pH and/or temperature changes that occur within the skeletal muscle and/or body cavities of a decomposing carcase shot and left in situ in this environment would be sufficient to inactivate FMDV. Study pigs (n = 30), cattle (6), sheep (6) and goats (8) were shot in one of four locations in Queensland. Carcase temperature and pH and ambient temperature were measured every 15-60 min for up to 46 h in two sites per animal: central (thoracic/abdominal cavity) and peripheral (skeletal muscle) or brain. A target pH ≤ 6.0 at any time and/or a target temperature ≥ 43°C for ≥ 7 h or ≥ 49°C for ≥ 1 h were used as proxies for achievement of FMDV inactivation. The target temperature was achieved in only one goat carcase. However, within 16 h of death, the target central and/or peripheral pH was attained in 88-100% of pig, cattle and sheep carcases. Increasing hours since death and death in the late morning/afternoon, relative to the early morning, were positively associated with attaining the target central carcase pH. This preliminary study provided evidence that FMDV inactivation may be achieved in the skeletal muscle and/or body cavities of carcases left under northern Australian conditions, though further work on pH changes in bone marrow are required.

Transcriptional gene silencing limits CXCR4-associated depletion of bone marrow CD34+ cells in HIV-1 infection.

Hematological abnormalities that include changes in bone marrow, such as in anemia and pancytopenia, are common among HIV-infected patients, particularly in the advanced stage of disease. Such abnormalities may be caused by a reduced bone marrow function for hematopoiesis. The aim of this study was to determine whether transcriptional gene silencing can help to preserve the hosts' hematopoietic potential in addition to peripheral CD4+ T cells against CCR5-tropic HIV infection. NOD/SCID/JAK3null (NOJ) mice were transplanted with human cord-derived CD34+ cells with or without transduction with a lentiviral vector expressing a promoter-targeting shRNA called PromA. At 16 weeks after transplantation, mice engrafted with CD34+ cells were infected with CCR5-tropic HIV-1JRFL. At week 2 postinfection, HIV replication was observed in peripheral blood mononuclear cells and splenocytes. In mice transplanted with unmanipulated CD34+ cells, viral replication was accompanied by a loss of peripheral/spleen CD4+CCR5+ T cells. Interestingly, bone marrow CD34+ cells in HIV-infected mice were also depleted, but in a CXCR4-associated manner. Conversely, the lentiviral transfer of PromA in CD34+ cells prior to transplantation rendered the humanized NOJ mice resistant to HIV replication in CD4+ T cells, resulting in better preservation of peripheral/spleen CD4+CCR5+ T cells and bone marrow CD34+ cells at 2 weeks after infection. These results indicate that stable gene transfer of PromA to hematopoietic stem cells not only limited HIV replication but also led to preservation of different subsets of hematopoietic cells, including bone marrow stem/progenitor cells and CD4+ T cells.

Age and sex analysis of the modic changes in the vertebrae

<p class="abstract"><strong>Background:</strong> Modic changes are common bone marrow and end plate changes that appear on magnetic resonance imaging of the lumbar spine. These changes are clinically associated with back pain and are generally classified into three types. In this study, we aimed to determine the frequency of patients with end plate deformities according to age and sex in their vertebrae.</p><p class="abstract"><strong>Methods:</strong> The study was performed on 100 patients (50 females, 50 males) who were admitted to Konya Education Research Hospital and thoracic region bone structures screened with MRI. </p><p class="abstract"><strong>Results:</strong> Modic changes were observed most at L4-L5 levels.</p><p class="abstract"><strong>Conclusions:</strong> We believe that the results obtained in our study will be beneficial in the surgeon, radiology and anatomy training.</p>

Mesenchymal stromal cells induce a permissive state in the bone marrow that enhances G-CSF-induced hematopoietic stem cell mobilization in mice

Mesenchymal stromal cells (MSCs) support hematopoietic stem cells (HSCs) in vivo and enhance HSC engraftment and hematopoietic recovery upon cotransplantation with HSCs. These data have led to the hypothesis that MSCs may affect the HSC niche, leading to changes in HSC retention and trafficking. We studied the effect of MSC administration on the HSC compartment in the bone marrow (BM) in mice. After injection of MSCs, HSC numbers in the BM were decreased coinciding with an increased cell cycle activity compared with phosphate-buffered saline (PBS)-injected controls. Furthermore, the frequency of macrophages was significantly reduced and niche factors including Cxcl12, Scf, and Vcam were downregulated in endosteal cells. These BM changes are reminiscent of events associated with granulocyte colony-stimulating factor (G-CSF)-induced hematopoietic stem and progenitor cell (HSPC) mobilization. Interestingly, coadministration of MSCs and G-CSF resulted in a twofold increase in peripheral blood HSPC release compared with injection of G-CSF alone, whereas injection of MSCs alone did not induce HSPC mobilization. After intravenous administration, MSCs were only observed in the lungs, suggesting that they exert their effect on the HSC niche through a soluble mediator. Therefore, we tested the hypothesis that MSC-derived extracellular vesicles (EVs) are responsible for the observed changes in the HSC niche. Indeed, administration of EVs resulted in downregulation of Cxcl12, Scf, and Vcam and enhanced G-CSF-induced HSPC mobilization at similar levels as MSCs and G-CSF. Together, these data indicate that MSCs induce a permissive state in the BM, enhancing HSPC mobilization through the release of EVs.

The Bone Does Not Predict the Brain in Sturge-Weber Syndrome.

It has been hypothesized that skull marrow signal alteration may represent an early disease manifestation of Sturge-Weber syndrome before development of its intracranial manifestations. We alternatively hypothesized that intraosseous changes are associated with the overlying port-wine stain rather than the intracranial stigmata of Sturge-Weber syndrome and hence are not a predictor of brain involvement. MR imaging of children presenting with port-wine stain and/or Sturge-Weber syndrome between 1998 and 2017 was evaluated by 2 pediatric neuroradiologists for marrow signal abnormality and pial angioma and other Sturge-Weber syndrome features: ocular hemangioma, atrophy, and white matter changes (advanced myelination). Groups were divided into port-wine stain-only (without intracranial Sturge-Weber syndrome features) and Sturge-Weber syndrome (the presence of cerebral pial angioma). The χ2 test was performed to evaluate the association between port-wine stain and bone marrow changes and between osseous change and pial angioma. We reviewed 139 cases: 40 with port-wine stain-only and 99 with Sturge-Weber syndrome with pial angioma. Fifteen of 99 cases of Sturge-Weber syndrome had no port-wine stain. In the port-wine stain-only cohort, 78% had ipsilateral bony changes and 17% had no intraosseous changes. In the Sturge-Weber syndrome cohort, 84/99 had associated port-wine stain, 91% (P < .01) had bony changes ipsilateral to the port-wine stain or had no bone changes in the absence of port-wine stain, and 77% (P = .27) had bony changes ipsilateral to a cerebral pial angioma. Eighty percent of patients with Sturge-Weber syndrome who lacked a port-wine stain also lacked marrow changes. Five patients with bilateral port-wine stain and bilateral marrow changes had only a unilateral pial angioma. Intraosseous marrow changes are strongly associated with facial port-wine stain; no significant association was found between pial angioma and bone marrow changes.

Acute Myeloid Leukemia in a Dog Chronically Infected with Leishmania spp. and Other Infectious Agents

Background: Rare studies have described the association of hematopoietic tumors and canine visceral leishmaniosis, however the association between the parasitary disease and neoplasia is still not well established in dogs. Thus, the aim of the present study was to report a case of acute myeloid leukemia (AML) in a dog infected by Leishmania spp. and otherinfectious agents.Case: A 8-year-old, male Poodle, was brought to the Veterinary Hospital from Universidade Federal Rural do Semi-Árido. The dog had a history of recurrent tick-borne diseases, such as anaplasmosis, over the previous ten months. On physical examination, pale mucosa, enlargement of popliteal lymph nodes, onychogryphosis, purulent nasal discharge, and bilateralblepharitis with purulent discharge were observed. The dog was skinny and infested with ticks. The blood cell count revealed normocytic, normochromic anemia and leukocytosis (38.000/mm3) with neutrophilia (30.020/mm3). Serum biochemical tests demonstrated hyperproteinemia due to hyperglobulinemia, hypoalbuminemia, and an albumin:globulin ratio of 0.30. The immunochromathographic test for leishmaniasis was negative. The alterations observed in the bone marrow cytological analysis were suggestive of AML, and Anaplasma spp., Hepatozoon spp., and amastigote forms of Leishmania spp. were observed inside bone marrow cells. After diagnosis, a decision to euthanize the animal was made.Discussion: Few studies have demonstrated the presence of hematopoietic neoplasia in dogs chronically and simultaneously infected with multiple pathogens. A case of multiple myeloma in a dog associated with infection by Ehrlichia canis, A. phagocytophilum, L. infantum, and Dirofilaria immitis is described. Another study reported B-cell lymphoma in a dog with E. canis and Histoplasma capsulatum infection. The pathogenesis of AML in the reported dog might be associated with continuous antigenic stimulation and chronic inflammation caused by the infectious agents. The pathological changes in bone marrow caused by Leishmania are well described, and different combinations of hypoplasia, hyperplasia, or dysplasia of all hematopoietic lineages can occur. The inflammation and chronic stimulation of hematopoiesis can lead to an increased risk of changes in the genetic material of the hematopoietic precursor cells. Thus, there is an increased chance of generation of mutated clones, resulting in hematopoietic malignancies. Immunosuppression is a common condition present in numerous types of neoplasia, especially in those with hematopoietic origins, which increases the vulnerability to opportunistic diseases. In humans, the presence of concomitant neoplasia and leishmaniasis is well documented, However, there are very few veterinary medicine studies on the association between neoplasia and canine visceral leishmaniosis. Cases of hematopoietic tumors, such as multiple myeloma, and multicentric, cutaneous, and cardiac lymphomas, have been described in dogs with leishmaniasis. To the best of our knowledge, this is possibly the first report implicating pathogens of the genera Leishmania, Anaplasma and Hepatozoon as contributors in the etiopathogenesis of AML in the studied animal. Based on all clinical and laboratory findings, we theorize that the prolonged antigenic stimulation and chronic inflammationcaused by the infectious agents played a crucial role in the development of leukemia in the dog.Keywords: myeloproliferative disorder, hemoparasites, canine leishmaniasis.

Elucidation of the pathology and tissue distribution of Lagovirus europaeus GI.2/RHDV2 (rabbit haemorrhagic disease virus 2) in young and adult rabbits (Oryctolagus cuniculus)

Lagovirus europaeus GI.2, also known as RHDV2 or RHDVb, is an emerging virus that causes rabbit haemorrhagic disease (RHD) in European rabbits (Oryctolagus cuniculus). In contrast to L. europaeus GI.1 (or RHDV/RHDVa) viruses that are only pathogenic for adults, GI.2 causes clinical disease in both adults and kittens. However, detailed descriptions of the pathology of this virus that may provide insight into its pathogenicity and emergence are lacking. Using an Australian GI.2 field strain isolated in 2015, we provide the first detailed description of pathology, viral antigen distribution and tissue load of GI.2 in adult and 5-week old New Zealand white rabbits using histology, immunohistochemistry and RT-qPCR. Liver was the target organ, but in contrast to GI.1 viruses, lesions and inflammatory responses did not differ between adults and kittens. Lymphocytic inflammation, proposed to be protective in kittens infected with GI.1, was notably absent. We also present the first descriptions of bone marrow changes in RHD, including decreased myeloid-to-erythroid ratio. Consistent with other pathogenic lagoviruses, intracellular viral antigen was demonstrated in hepatocytes and cells of the mononuclear phagocytic system. In terminal stages of disease, viral loads were highest in liver, serum and spleen. Despite the small sample size, our data suggest that unlike early European GI.2 strains, the pathogenicity of the Australian GI.2 virus is similar to GI.1 viruses. Additionally, GI.2 was fatal for all (n = 5) inoculated kittens in this study. This may significantly alter RHD epidemiology in the field, and may impact biocontrol programs for invasive rabbits in Australia where GI.1 viruses are intentionally released.

Changes of Leukemia Stem Cells in Acute Myeloid Leukemia before and after Treatment

To investigate the presence of leukemia stem cells (LSC) in acute myeloid leukemia (AML) and find out the relative position of leukemia cells in the figures of flow cytometry, and to analyze the relationship between minimal residual diseases (MRD) and the level of LSC, so as to explore the correlation of LSC changes with the curative effect and the prognosis during chemical therapy. A total of 85 samples were collected from 50 AML (except M3) patients, including 50 samples from the newly diagnosed patients, 7 samples of AML patients with non-remission and 28 samples of AML patients with complete remission. All samples were used for detection of LSC from immune phenotype of CD34+/CD38-/CD123+ by flow cytometry. The detection of immune phenotypic of leukemia cells was performed in the newly diagnosed patients. The detection of leukemia- associated immune phenotypes (LAIP) was implemented in the non-newly diagnosed patients. The LSC was identified in the CD34+/ CD38-/ CD123+ in AML and consistent with the relative position of the leukemia cell in flow cytometry figures. Statistical analysis showed significant difference in LSC content between the newly diagnosed AML group and the post-chemotherapy complete remission group(P<0.01),but did not between the newly diagnosed AML group and the post-chemotherapy non-remission group(P>0.05).There was significant positive correlation between the LSC content and MRD level in 28 AML patients with complete remission (r=0.680,P<0.01). LSC exist in AML and the relative position are consistent with the leukemia cells in flow cytometry figures, the size characteristics and weak expression of CD45 are also similar to leukemia cells. The proportion of LSC decreases after chemotherapy. Detecting and tracking the LSC changes in bone marrow and combination with detecting minimal resident disease(MRD) may contribute to evaluate the theraputic efficacy and prognosis of leukemia patients.

Developing a reference MRI database for temporomandibular joints in healthy children and adolescents.

Recognition of normal temporomandibular joints (TMJs) is essential to assess arthropathic changes. Few, if any, prior studies have evaluated the morphological appearance of growing TMJs by magnetic resonance (MR) examinations in the pediatric population. This study aimed to determine normative osseous appearance of growing TMJs according to age and gender, both qualitatively and quantitatively, concerning structural and bone marrow changes. From 1,036 MR scans screened, one joint was included from each of 157 patients (76% female; 2-18 years) presenting with at least one normal-appearing TMJ was included. Quantitatively, mandibular condyle was characterized by measuring the following: (i) head-neck angle, (ii) anteversion angle, (iii) condylar dimensions (mediolateral, craniocaudal and anteroposterior [AP]) and (iv) condylar volume. Furthermore, qualitative categorization of condylar shape, into one of three types, and condylar bone marrow type was performed. The head-neck angle significantly correlated with age (bivariable regression β =0.60, P<0.001), indicating an increase of 1.6 degrees per year. Except for AP diameter of condyles, all other mandibular dimensions and condylar volume increased with age (β =0.20-0.59, P≤0.001-0.004). Significant age difference was observed among the different condylar shapes (P<0.001), indicating a change from rounded head without anterior tilt to rectangular head with anterior tilt. Lastly, mandibular condylar size, measured by volume and by AP and mediolateral dimensions, appeared larger in males. The morphology of the mandibular condyles changes with age. During development, the shape of the condyles changes from round to rectangular in contour with the development of the anterior condylar tilt, as measured by the head-neck angle.

Insufficiency Fractures After Radiation Therapy: An Update

Purpose of Review Radio therapy, alone or in combination with surgery and/or chemotherapy, is commonly used to treat a variety of neoplasms, resulting in effective local tumor control. Unfortunately radiation therapy can also change the structure of the skeletal system, leading to edema, vascular congestion, areas of hemorrhage, loss of cellularity, focal bone marrow changes, fatty transformation, osteitis, hematopoietic marrow regeneration, osteolysis of symphysis pubis or sacroiliac joints, avascular necrosis, insufficiency fractures, osteoradionecrosis, and radiation-induced neoplasms.

IL-17A induced hematopoietic reprogramming produces both PMN and MDSC at the post-acute stage of inflammation.

Abstract Our previous study suggests that polymorphonuclear leukocyte (PMN) response is enhanced at the post-acute stage of murine colitis due to changes in bone marrow (BM) myelopoiesis. Herein, we report that hematopoietic reprogramming during the post-acute phase of inflammation produces myeloid derived suppressor cells (MDSC) that co-infiltrate the intestine with PMN. Employing Percoll density gradients, we analyzed dynamic changes to the myeloid compartment by separating BM leukocytes from DSS colitis-to-recovery mice into four density-increasing bands with myeloid leukocytes enriched in bands III (50–60%) and IV (60–70%). Band III was comprised of monocytes and low-density granulocytes; both confirmed to be M-MDSCs and G-MDSCs, respectively, by displaying potent inhibition of T-cell proliferation. Despite significant decreases in the PMN population, presumably caused by mobilization into inflamed tissues, MDSC numbers significantly increase beginning at the post-acute stage of colitis. Furthermore, MDSC numbers do not return to baseline until late in the recovery stage. The expanded G-MDSCs also showed increased CXCR2 expression, which guides egress out of BM, and produced ROS upon PMA activation. Adoptive transfer assays demonstrated that functionally enhanced PMN infiltrated the intestine at the post-acute stage to clear the existing inflammatory reaction, while MDSC accumulated in the intestine during recovery suggesting a role in tissue repair. IL-17A signaling at the post-acute stage of inflammation likely induced hematopoietic reprogramming of the myeloid compartment, as its neutralization blocked expansion and infiltration of both PMN and MDSC.

Morfologicheskie izmeneniya kostnogo mozga pri ehksperimental'nom opistorkhoze

Morfologicheskie izmeneniya kostnogo mozga pri ehksperimental'nom opistorkhoze

Bone Marrow Changes Induced by Guiera Senegalensis in Acetic Acid-induced Colitis in Wistar Rats

Bone Marrow Changes Induced by Guiera Senegalensis in Acetic Acid-induced Colitis in Wistar Rats

From radiation osteitis to osteoradionecrosis: incidence and MR morphology of radiation-induced sacral pathologies following pelvic radiotherapy.

To investigate the incidence rate, time-to-onset and recovery, MRI morphology and occurrence of insufficiency fractures in radiation-induced changes in the sacrum following pelvic radiotherapy. 410 patients with pelvic malignancies treated with radiotherapy were reviewed. Follow-up was 1-124 months (mean 22 months). Serial MRI (average four studies/patient) were analysed using a new semi-quantitative score (Radiation-Induced Sacral Changes=RISC). A size category (I/II/III), a type category for MR signal morphologies (a/b/c) and sacral insufficiency fractures (+/-) were applied. Seventy-two patients (17.6 %) were found to have new pathological signal changes. Radiation osteitis was documented in 83.3 % (60/72, RISC stage a + b), and definite osteonecrosis (stage c) in 12 patients (16.7 %, 12/72). Thirty-one patients (43.1 %) had sacral insufficiency fractures. Initial bone marrow signal changes were found 1-35 months (median 4 months) after radiotherapy. The maximum manifestation of radiation-induced signal changes occurred after 1-35 months (mean 11 months). Fifty-six cases (77.8 %) showed a significant signal recovery within 16.5 months. Radiation-induced bone marrow changes appear with a high incidence at the sacrum with an early onset and frequent recovery. The majority presented a pattern of radiation osteitis, whereas osteoradionecrosis was proportionately rare. • Radiation-induced sacral bone marrow changes appear frequently (17.6 %) following pelvic radiotherapy. • Insufficiency fractures are common late effects (43 %). • Radiation osteitis develops early (4 mo), withrecovery between 16.5 and 39.5 months. • Definite radiological osteoradionecrosis is proportionately rare (3 %). • A 3-stage classification system simplifies and standardizes the morphological disease staging.

Targeted Next-Generation Sequencing Is a Sensitive Tool for Differential Diagnosis of Myelodysplastic Syndromes in Bone Marrow Trephines

Myelodysplastic syndromes are hematological neoplasias in which immunohistologic examination of bone marrow trephines is important for a definite diagnosis. Unequivocal distinction from reactive bone marrow changes is, however, sometimes difficult. Because neoplastic clones in myelodysplastic syndrome carry mutations in recurrent genes, mutation detection by targeted next-generation sequencing may be a useful support for differential diagnosis. To elucidate the accuracy of this approach in the clinical diagnostic setting, we analyzed single and consecutive bone marrow trephines processed for immunohistologic examination from 145 patients by targeted next-generation sequencing of 12 genes recurrently mutated in myelodysplastic syndromes. Of 110 patients with immunohistologic unequivocal diagnosis, 41 of 47 with myelodysplastic syndrome carried mutations. In 14 consecutive samples available from these patients, remissions were accompanied by loss of mutations and ongoing disease with persisting mutations. Of 35 samples with indefinite immunohistologic appearance, 22 developed clinical unequivocal myelodysplastic syndrome in the further course, and 19 carried mutations already in the initial biopsy, which persisted in consecutive samples available from 13 patients. No mutation was detected in any initial and consecutive sample of 13 patients with indefinite immunohistologic appearance without clinical unequivocal myelodysplastic syndrome in the further course. We conclude that targeted next-generation sequencing is an accurate tool for differential diagnosis of myelodysplastic syndrome in the clinical diagnostic setting.