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In addressing the critical role of emotional context in patient–clinician conversations, this study conducted a comprehensive sentiment analysis using BERT, RoBERTa, GPT-2, and XLNet. Our dataset includes 185 h of Greek conversations focused on hematologic malignancies. The methodology involved data collection, data annotation, model training, and performance evaluation using metrics such as accuracy, precision, recall, F1-score, and specificity. BERT outperformed the other methods across all sentiment categories, demonstrating its effectiveness in capturing the emotional context in clinical interactions. RoBERTa showed a strong performance, particularly in identifying neutral sentiments. GPT-2 showed promising results in neutral sentiments but exhibited a lower precision and recall for negatives. XLNet showed a moderate performance, with variations across categories. Overall, our findings highlight the complexities of sentiment analysis in clinical contexts, especially in underrepresented languages like Greek. These insights highlight the potential of advanced deep-learning models in enhancing communication and patient care in healthcare settings. The integration of sentiment analysis in healthcare could provide insights into the emotional states of patients, resulting in more effective and empathetic patient support. Our study aims to address the gap and limitations of sentiment analysis in a Greek clinical context, an area where resources are scarce and its application remains underexplored. [ABSTRACT FROM AUTHOR]

Enabling patients to actively document their health information significantly improves understanding of how therapies work, disease progression, and overall life quality affects for those living with chronic disorders such as hematologic malignancies. Advancements in artificial intelligence, particularly in areas such as natural language processing and speech recognition, have resulted in the development of interactive tools tailored for healthcare. This paper introduces an innovative conversational agent tailored to the Greek language. The design and deployment of this tool, which incorporates sentiment analysis, aims at gathering detailed family histories and symptom data from individuals diagnosed with hematologic malignancies. Furthermore, we discuss the preliminary findings from a feasibility study assessing the tool's effectiveness. Initial feedback on the user experience suggests a positive reception towards the agent's usability, highlighting its potential to enhance patient engagement in a clinical setting. [ABSTRACT FROM AUTHOR]

The in vitro evaluation of 3D scaffolds for bone tissue engineering in mono-cultures is a common practice; however, it does not represent the native complex nature of bone tissue. Co-cultures of osteoblasts and osteoclasts, without the addition of stimulating agents for monitoring cellular cross-talk, remains a challenge. In this study, a growth factor-free co-culture of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and human peripheral blood mononuclear cells (hPBMCs) has been established and used for the evaluation of 3D-printed scaffolds for bone tissue engineering. The scaffolds were produced from PLLA/PCL/PHBV polymeric blends, with two composite materials produced through the addition of 2.5% w/v nanohydroxyapatite (nHA) or strontium-substituted nanohydroxyapatite (Sr-nHA). Cell morphology data showed that hPBMCs remained undifferentiated in co-culture, while no obvious differences were observed in the mono- and co-cultures of hBM-MSCs. A significantly increased alkaline phosphatase (ALP) activity and osteogenic gene expression was observed in co-culture on Sr-nHA-containing scaffolds. Tartrate-resistant acid phosphatase (TRAP) activity and osteoclastogenic gene expression displayed significantly suppressed levels in co-culture on Sr-nHA-containing scaffolds. Interestingly, mono-cultures of hPBMCs on Sr-nHA-containing scaffolds indicated a delay in osteoclasts formation, as evidenced from TRAP activity and gene expression, demonstrating that strontium acts as an osteoclastogenesis inhibitor. This co-culture study presents an effective 3D model to evaluate the regenerative capacity of scaffolds for bone tissue engineering, thus minimizing time-consuming and costly in vivo experiments. [ABSTRACT FROM AUTHOR]

Byline: Dimitra. Koumaki, Vasiliki. Koumaki, Vrettos. Haniotis, Alexander. Katoulis, Sotirios. Boumpoucheropoulos, Maria. Stefanidou, Charalampos. Pontikoglou, George. Bertsias, George. Evangelou, Kyriaki. Zografaki, Aikaterini. Mantaka, Sabine. Krueger-Krasagakis, Konstantinos. Krasagakis Sir, A 57-year-old [...]

Myelodysplastic syndromes include a broad spectrum of malignant myeloid disorders that are characterized by dysplastic ineffective hematopoiesis, reduced peripheral blood cells counts and a high risk of progression to acute myeloid leukemia. The disease arises primarily because of accumulating chromosomal, genetic and epigenetic changes as well as immune-mediated alterations of the hematopoietic stem cells (HSCs). However, mounting evidence suggests that aberrations within the bone marrow microenvironment critically contribute to myelodysplastic syndrome (MDS) initiation and evolution by providing permissive cues that enable the abnormal HSCs to grow and eventually establish and propagate the disease. Mesenchymal stromal cells (MSCs) are crucial elements of the bone marrow microenvironment that play a key role in the regulation of HSCs by providing appropriate signals via soluble factors and cell contact interactions. Given their hematopoiesis supporting capacity, it has been reasonable to investigate MSCs' potential involvement in MDS. This review discusses this issue by summarizing existing findings obtained by in vitro studies and murine disease models of MDS. Furthermore, the theoretical background of targeting the BM-MSCs in MDS is outlined and available therapeutic modalities are described. [ABSTRACT FROM AUTHOR]

Myeloid-derived suppressor cells (MDSCs) are immature cells of myeloid origin that have gained researchers' attention, as they constitute promising biomarkers and targets for novel therapeutic strategies (i.e., blockage of development, differentiation, depletion, and deactivation) in several conditions, including neoplastic, autoimmune, infective, and inflammatory diseases, as well as pregnancy, obesity, and graft rejection. They are characterised in humans by the typical immunophenotype of CD11b+CD33+HLA-DR–/low and immune-modulating properties leading to decreased T-cell proliferation, induction of T-regulatory cells (T-regs), hindering of natural killer (NK) cell functionality, and macrophage M2-polarisation. The research in the field is challenging, as there are still difficulties in defining cell-surface markers and gating strategies that uniquely identify the different populations of MDSCs, and the currently available functional assays are highly demanding. There is evidence that MDSCs display altered frequency and/or functionality and could be targeted in immune-mediated and malignant haematologic diseases, although there is a large variability of techniques and results between different laboratories. This review presents the current literature concerning MDSCs in a clinical point of view in an attempt to trigger future investigation by serving as a guide to the clinical haematologist in order to apply them in the context of precision medicine as well as the researcher in the field of experimental haematology. [ABSTRACT FROM AUTHOR]

Objective: The characterization of microRNAs (miRNA) in recent years is an important advance in the field of gene regulation. To this end, several approaches for miRNA expression analysis and various bioinformatics tools have been developed over the last few years. It is a common practice to analyze miRNA PCR Array data using the commercially available software, mostly due to its convenience and ease-of-use. Results: In this work we present miRkit, an open source framework written in R, that allows for the comprehensive analysis of RT-PCR data, from the processing of raw data to a functional analysis of the produced results. The main goal of the proposed tool is to provide an assessment of the samples' quality, perform data normalization by endogenous and exogenous miRNAs, and facilitate differential and functional enrichment analysis. The tool offers fast execution times with low memory usage, and is freely available under a ΜΙΤ license from https://bio.tools/mirkit. Overall, miRkit offers the full analysis from the raw RT-PCR data to functional analysis of targeted genes, and specifically designed to support the popular miScript miRNA PCR Array (Qiagen) technology. [ABSTRACT FROM AUTHOR]

Summary: The regimen of 5‐azacytidine for patients with myelodysplastic syndrome (MDS) has remained unchanged since its first approval. Although several modifications have since been made and delays and dose reductions are common especially during the first treatment cycles, there are minimal data on the prognostic effect of these modifications. In this study, based on data from 897 patients with MDS treated with 5‐azacytidine recorded in a national registry, the effect of treatment delays and dose reductions on response, transformation to acute myeloid leukaemia, and survival (after 5‐azacytidine initiation, OST) were analysed. Delays during the first two cycles were noted in 150 patients (16·7%) and were found to adversely affect OST independently of the International Prognostic Scoring System score [hazard ratio (HR), 1·368; P = 0·033] or pre‐existing neutropenia (HR, 1·42; P = 0·015). In patients achieving a response, delays before response achievement were correlated with its type (complete remission, 2·8 days/cycle; partial remission, 3·3 days/cycle; haematologic improvement, 5·6 days/cycle; P = 0·041), while delays after response achievement did not have any effect on retention of response or survival. Dose reductions were found to have no prognostic impact. Based on our results, treatment delays especially during the first cycles should be avoided, even in neutropenic patients. This strict strategy may be loosened after achieving a favourable response. [ABSTRACT FROM AUTHOR]

This collection of cases describes some unusual urological tumors and complications related to urological tumors and their treatment. Case 1: A case of uretero-arterial fistula in a patient with long-term ureteral stenting for ureteral oncological stricture and a second case associated to retroperitoneal fibrosis were described. Abdominal CT, pyelography, cystoscopy were useful to show the origin of the bleeding. Angiography is useful for confirming the diagnosis and for subsequent positioning of an endovascular prosthesis which represents a safe approach with reduced post-procedural complications. Case 2: A case of patient who suffered from interstitial pneumonitis during a cycle of intravesical BCG instillations for urothelial cancer. The patient was hospitalized for more than two weeks in a COVID ward for a suspected of COVID-19 pneumonia, but he did not show any evidence of SARS-CoV-2 infection during his hospital stay. Case 3: A case of a young man with a functional urinary bladder paraganglioma who was successfully managed with complete removal of the tumor, leaving the urinary bladder intact. Case 4: A case of a 61 year old male suffering from muscle invasive bladder cancer who was admitted for a radical cystectomy and on the eighth postoperative day developed microangiopathic hemolytic anemia and thrombocytopenia, which clinically defines thrombotic microangiopathy. [ABSTRACT FROM AUTHOR]

Clonal B-cell lymphocytosis of marginal zone origin (CBL-MZ) is a recently described entity characterized by the presence of clonal B cells in the blood and/or bone marrow (BM) with morphologic and immunophenotypic features consistent with marginal zone derivation in otherwise healthy individuals. CBL-MZ is commonly associated with paraproteinemia, usually immunoglobulin M (IgM), raising diagnostic difficulties from Waldenstrom macroglobulinemia (WM). The aim of the present study was to determine the presence of MYD-88 L265P mutation in a well-characterized series of CBL-MZ to identify cases that may in fact represent WM. Fifty-three CBL-MZ cases were retrospectively evaluated. MYD-88 L265P mutation was determined by allele-specific polymerase chain reaction in blood and/or BM mononuclear cells. Almost half of the CBL-MZ cases (49%) were associated with paraproteinemia mainly of the IgM type (65%). MYD-88 L265P mutation was identified in 10 cases (19%). These cases may truly represent WM, whereas 43 cases (81%) are still classified as CBL-MZ. Mutated cases were all associated with paraproteinemia compared with 37% of the nonmutated ones (P < .0001). In addition, mutated cases displayed more frequently CD38 and CD25 positivity (P = .002 and P = .005, respectively). Moreover, cases without paraproteinemia presented more frequently with lymphocytosis, irrespective of the presence of the MYD-88 mutation (P = .02). The present study demonstrates that MYD-88 L265P mutation may represent the only sensitive marker for the differentiation of CBL-MZ from probable WM. However, further studies are warranted to better define the biological significance of MYD-88 L265P mutation and to clarify whether the presence of the mutation establishes WM diagnosis or that it can also be present in borderline cases associated with paraproteinemia. [ABSTRACT FROM AUTHOR]

Background: In view of the current interest in exploring the clinical use of mesenchymal stem cells (MSCs) from different sources, we performed a side-by-side comparison of the biological properties of MSCs isolated from the Wharton's jelly (WJ), the most abundant MSC source in umbilical cord, with bone marrow (BM)-MSCs, the most extensively studied MSC population. Methods: MSCs were isolated and expanded from BM aspirates of hematologically healthy donors (n = 18) and from the WJ of full-term neonates (n = 18). We evaluated, in parallel experiments, the MSC immunophenotypic, survival and senescence characteristics as well as their proliferative potential and cell cycle distribution. We also assessed the expression of genes associated with the WNT- and cell cycle-signaling pathway and we performed karyotypic analysis through passages to evaluate the MSC genomic stability. The hematopoiesis-supporting capacity of MSCs from both sources was investigated by evaluating the clonogenic cells in the non-adherent fraction of MSC co-cultures with BM or umbilical cord blood-derived CD34+ cells and by measuring the hematopoietic cytokines levels in MSC culture supernatants. Finally, we evaluated the ability of MSCs to differentiate into adipocytes and osteocytes and the effect of the WNT-associated molecules WISP-1 and sFRP4 on the differentiation potential of WJ-MSCs. Results: Both ex vivo-expanded MSC populations showed similar morphologic, immunophenotypic, survival and senescence characteristics and acquired genomic alterations at low frequency during passages. WJ-MSCs exhibited higher proliferative potential, possibly due to upregulation of genes that stimulate cell proliferation along with downregulation of genes related to cell cycle inhibition. WJ-MSCs displayed inferior lineage priming and differentiation capacity toward osteocytes and adipocytes, compared to BM-MSCs. This finding was associated with differential expression of molecules related to WNT signaling, including WISP1 and sFRP4, the respective role of which in the differentiation potential of WJ-MSCs was specifically investigated. Interestingly, treatment of WJ-MSCs with recombinant human WISP1 or sFRP4 resulted in induction of osteogenesis and adipogenesis, respectively. WJ-MSCs exhibited inferior hematopoiesis-supporting potential probably due to reduced production of stromal cell-Derived Factor-1α, compared to BM-MSCs. Conclusions: Overall, these data are anticipated to contribute to the better characterization of WJ-MSCs and BM-MSCs for potential clinical applications. [ABSTRACT FROM AUTHOR]

Chronic idiopathic neutropenia (CIN) is an acquired disorder of granulopoiesis characterized by increased apoptosis of the bone marrow (BM) granulocytic progenitor cells under the influence of pro-inflammatory mediators and oligoclonal/monoclonal T-lymphocytes. Because patients with immune-mediated BM failure display frequently paroxysmal nocturnal hemoglobinuria (PNH)-type cells in the peripheral blood (PB), we investigated the possible existence of PNH-type cells in 91 patients with CIN using flow cytometry. The patients displayed increased proportions of PNH-type glycophorin A+/CD59dim and glycophorin A+/CD59− red blood cells (RBCs), FLAER−/CD24− granulocytes, and FLAER−/CD14− monocytes, compared to controls ( n = 55). A positive correlation was found between the proportions of PNH-type RBCs, granulocytes, and monocytes and an inverse correlation between the number of PB neutrophils and the proportions of PNH-type cell populations. The number of patients, displaying percentages of PNH-type cells above the highest percentage observed in the control group, was significantly increased among patients with skewed compared to those with normal T-cell receptor repertoire suggesting that T-cell-mediated immune processes underlie the emergence of PNH-type cells in CIN. Our findings suggest that patients with CIN display PNH-type cells in the PB at a high frequency corroborating the hypothesis that CIN belongs to the immune-mediated BM failure syndromes. [ABSTRACT FROM AUTHOR]

The article focuses on the bone marrow mesenchymal stem/stromal cells (BM-MSCs) in the disease progression of B-cell lymphoma. It discusses the anti-apoptotic and chemotactic effect of malignant bone marrow (BM) and healthy donor (HD) derived BM-MSC, determination of MSC's incidence related bone marrow mononuclear cell (BMMC) fraction with the help of colony forming unit-fibroblast (CFU-F) assay.

Mucormycosis is a rare fungal infection that poses a severe threat to immunocompromised patients. In the case presented herein, a 56-year-old leukemic patient, who was treated with amphotericin B and posaconazole, was scheduled for surgical resection of mucormycosis lesions that had spread to the thorax and abdomen. Surgery was aggressive and the resection involved the left lateral thoracoabdominal wall, 2 ribs, the left diaphragm, and the spleen. The patient tolerated the procedure well and the leukemia went into remission. Aggressive surgery can benefit immunocompromised patients with mucormycosis. [ABSTRACT FROM AUTHOR]

Similar to other adult tissue stem/progenitor cells, bone marrow mesenchymal stem/stromal cells ( BM MSCs) exhibit heterogeneity at the phenotypic level and in terms of proliferation and differentiation potential. In this study such a heterogeneity was reflected by the CD200 protein. We thus characterized CD200pos cells sorted from whole BM MSC cultures and we investigated the molecular mechanisms regulating CD200 expression. After sorting, measurement of lineage markers showed that the osteoblastic genes RUNX2 and DLX5 were up-regulated in CD200pos cells compared to CD200neg fraction. At the functional level, CD200pos cells were prone to mineralize the extra-cellular matrix in vitro after sole addition of phosphates. In addition, osteogenic cues generated by bone morphogenetic protein 4 ( BMP4) or BMP7 strongly induced CD200 expression. These data suggest that CD200 expression is related to commitment/differentiation towards the osteoblastic lineage. Immunohistochemistry of trephine bone marrow biopsies further corroborates the osteoblastic fate of CD200pos cells. However, when dexamethasone was used to direct osteogenic differentiation in vitro, CD200 was consistently down-regulated. As dexamethasone has anti-inflammatory properties, we assessed the effects of different immunological stimuli on CD200 expression. The pro-inflammatory cytokines interleukin-1β and tumour necrosis factor-α increased CD200 membrane expression but down-regulated osteoblastic gene expression suggesting an additional regulatory pathway of CD200 expression. Surprisingly, whatever the context, i.e. pro-inflammatory or pro-osteogenic, CD200 expression was down-regulated when nuclear-factor ( NF)-κB was inhibited by chemical or adenoviral agents. In conclusion, CD200 expression by cultured BM MSCs can be induced by both osteogenic and pro-inflammatory cytokines through the same pathway: NF-κB. [ABSTRACT FROM AUTHOR]

Aims: Endothelial progenitor cells (EPCs) are bone marrow-derived cells that are mobilized into the circulation to migrate and differentiate into mature endothelial cells contributing to post-natal physiological and pathological neovascularization. In this study, we evaluated circulating EPCs in patients with hypertrophic cardiomyopathy (HCM) and examined a potential association with clinical parameters of the disease.Methods and Results: We included 40 HCM patients and 23 healthy individuals. Using flow cytometry we measured EPCs in peripheral blood as two subpopulations of CD45-/CD34+/VEGFR2+ and CD45-/CD34+/CD133+ cells. Circulating CD45-/CD34+/VEGFR2+ cells were significantly increased in HCM patients in comparison with the controls (0.000238 ± 0.0003136 vs. 0.000057 ± 0.0001316, respectively, P = 0.002). However, there was no significant difference in the number of circulating CD45-/CD34+/CD133+ cells (0.003079 ± 0.0033288 vs. 0.002065 ± 0.0022173, respectively, P = 0.153). The CD45-/CD34+/VEGFR2+ subpopulation revealed a moderate correlation with LV mass index (r = 0.35, P = 0.026), while both EPC subpopulation levels showed strong positive correlations with th E/e' ratio (r = 0.423, P = 0.007 for CD45-/CD34+/VEGFR2+ and r = 0.572, P < 0.001 for CD45-/CD34+/CD133+).Conclusion: HCM patients showed an increased mobilization of EPCs compared with healthy individuals that correlated with diastolic dysfunction. Our findings may open up new dimensions in the pathophysiology, prognostication, and treatment of HCM. [ABSTRACT FROM AUTHOR]

Stem cells have great clinical significance in many cardiovascular diseases. However, there are limited data regarding the involvement of mesenchymal stem cells (MSCs) in the pathophysiology of arterial hypertension. The aim of this study was to investigate the circulation of MSCs in patients with essential hypertension. The authors included 24 patients with untreated essential hypertension and 19 healthy individuals. Using flow cytometry, MSCs in peripheral blood, as a population of CD45-/CD34-/CD90+ cells and also as a population of CD45-/CD34-/CD105+ cells, were measured. The resulting counts were translated into the percentage of MSCs in the total cells. Hypertensive patients were shown to have increased circulating CD45-/CD34-/CD90+ compared with controls (0.0069%±0.012% compared with 0.00085%±0.0015%, respectively; P=.039). No significant difference in circulating CD45-/CD34-/CD105+ cells was found between hypertensive patients' and normotensive patients' peripheral blood (0.018%±0.013% compared with 0.015%±0.014%, respectively; P=.53). Notably, CD45-/CD34-/CD90+ circulating cells were positively correlated with left ventricular mass index (LVMI) (r=0.516, P<.001). Patients with essential hypertension have increased circulating MSCs compared with normotensive patients, and the number of MSCs is correlated with LVMI. These findings contribute to the understanding of the pathophysiology of hypertension and might suggest a future therapeutic target. [ABSTRACT FROM AUTHOR]

It has been shown that bone marrow mesenchymal stromal cells (MSCs) from patients with myelodysplastic syndromes (MDSs) display defective proliferative potential. We have probed the impaired replicative capacity of culture-expanded MSCs in MDS patients ( n=30) compared with healthy subjects ( n=32) by studying senescence characteristics and gene expression associated with WNT/transforming growth factor-β1 (TGFB1) signaling pathways. We have also explored the consequences of the impaired patient MSC proliferative potential by investigating their differentiation potential and the capacity to support normal CD34+ cell growth under coculture conditions. Patient MSCs displayed decreased gene expression of the senescence-associated cyclin-dependent kinase inhibitors CDKN1A, CDKN2A, and CDKN2B, along with PARG1, whereas the mean telomere length was upregulated in patient MSCs. MDS-derived MSCs exhibited impaired capacity to support normal CD34+ myeloid and erythroid colony formation. No significant changes were observed between patients and controls in gene expression related to TGFB1 pathway. Patient MSCs displayed upregulated non-canonical WNT expression, combined with downregulated canonical WNT expression and upregulated canonical WNT inhibitors. MDS-derived MSCs displayed defective osteogenic and adipogenic lineage priming under non-differentiating culture conditions. Pharmacological activation of canonical WNT signaling in patient MDSs led to an increase in cell proliferation and upregulation in the expression of early osteogenesis-related genes. This study indicates abnormal WNT signaling in MSCs of MDS patients and supports the concept of a primary MSC defect that might have a contributory effect in MDS natural history. [ABSTRACT FROM AUTHOR]

The potential association between arterial stiffening and circulating endothelial progenitor cells ( EPCs) in patients with essential hypertension was investigated. Pulse wave velocity ( PWV) was used to evaluate arterial stiffness in 24 patients with essential hypertension and 19 healthy controls. Blood samples were taken and immunostained with antibodies against the cell surface markers CD34, CD45, and CD133. Using flow cytometry, EPCs as a population of CD45−/ CD34+/ CD133+ cells were measured. Hypertensive patients were not found to have higher levels of circulating CD45−/ CD34+/ CD133+ compared with the control group (0.0026%±0.0031% vs 0.0023%±0.0023%, respectively; P=.7). Correlation analysis revealed a strong association between the number of CD45−/ CD34+/ CD133+ cells and PWV ( r=0.58, P<.001), indicating that hypertensive patients with increased PWV have a greater percentage of CD45−/ CD34+/ CD133+ cells. Data showed a correlation between the number of circulating CD45−/ CD34+/ CD133+ cells and arterial stiffness, suggesting that those cells might have a role in arterial remodeling. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are multipotent adult stem cells that are present in practically all tissues as a specialized population of mural cells/pericytes that lie on the abluminal side of blood vessels. Originally identified within the bone marrow (BM) stroma, not only do they provide microenvironmental support for hematopoietic stem cells (HSCs), but can also differentiate into various mesodermal lineages. MSCs can easily be isolated from the BM and subsequently expand in vitro and in addition they exhibit intriguing immunomodulatory properties, thereby emerging as attractive candidates for various therapeutic applications. This review addresses the concept of BM MSCs via a hematologist's point of view. In this context it discusses the stem cell properties that have been attributed to BM MSCs, as compared to those of the prototypic hematopoietic stem cell model and then gives a brief overview of the in vitro and vivo features of the former, emphasizing on their immunoregulatory properties and their hematopoiesis-supporting role. In addition, the qualitative and quantitative characteristics of BM MSCs within the context of a defective microenvironment, such as the one characterizing Myelodysplastic Syndromes are described and the potential involvement of these cells in the pathophysiology of the disease is discussed. Finally, emerging clinical applications of BM MSCs in the field of hematopoietic stem cell transplantation are reviewed and potential hazards from MSC use are outlined. [ABSTRACT FROM AUTHOR]

Non chemotherapy drug-induced agranulocytosis is considered a potentially life-threatening idiosyncratic blood dyscrasia, thought to result from a partly elucidated immune and/or toxic damage on myelopoiesis, due to a multitude of drugs. Offending agents include clozapine, ticlopidine, antithyroid compounds, dipyrone, sulfasalzine, trimethropim/sulfomethoxazole, carmabazepine, and to a lesser extent, deferiprone (L1) and probably rituximab. Suspected drugs should be immediately stopped and, in symptomatic patients, once appropriate cultures have been obtained, broad-spectrum antibiotic treatment should be administered. Hematopoietic growth factors may be considered, specifically in patients with poor prognostic factors. Due to improved intensive care treatment and alertness of physicians the case fatality of the disorder has recently been decreased to 5%. [ABSTRACT FROM AUTHOR]

Lineage-priming is a molecular model of stem cell (SC) differentiation in which proliferating SCs express a subset of genes associated to the differentiation pathways to which they can commit. This concept has been developed for hematopoietic SCs, but has been poorly studied for other SC populations. Because the differentiation potential of human bone marrow mesenchymal stem cells (BM MSCs) remains controversial, we have explored the theory of lineage-priming applied to these cells. We show that proliferating primary layers and clones of BM MSCs have precise priming to the osteoblastic (O), chondrocytic (C), adipocytic (A), and the vascular smooth muscle (V) lineages, but not to skeletal muscle, cardiac muscle, hematopoietic, hepatocytic, or neural lineages. Priming was shown both at the mRNA (300 transcripts were evaluated) and the protein level. In particular, the master transactivator proteins PPARG, RUNX2, and SOX9 were coexpressed before differentiation induction in all cells from incipient clones. We further show that MSCs cultured in the presence of inducers differentiate into the lineages for which they are primed. Our data point out to a number of signaling pathways that might be activated in proliferating MSCs and would be responsible for the differentiation and proliferation potential of these cells. Our results extend the notion of lineage-priming and provide the molecular framework for inter-A, -O, -C, -V plasticity of BM MSCs. Our data highlight the use of BM MSCs for the cell therapy of skeletal or vascular disorders, but provide a word of caution about their use in other clinical indications. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to probe the mechanisms underlying anemia in patients with chronic idiopathic neutropenia (CIN) by evaluating parameters of bone marrow (BM) erythropoiesis. Patients and Methods: Ten CIN patients fulfilling the criteria of anemia of chronic disease, 27 nonanemic CIN patients, and 30 healthy volunteers were enrolled in the study. Reserves and survival characteristics of BM erythroid cells were evaluated using flow cytometry and clonogenic assays. Serum erythropoietin (EPO) was measured with ELISA. Expression of EPO receptors (EPORs) on BM erythroid cells was evaluated by flow cytometry and reverse-transcription polymerase chain reaction. Results: CIN patients display defective erythropoiesis in addition to previously reported impaired granulopoiesis. Patients have low number of CD34+/CD71+ progenitor and CD36−/ Glycophorin A+ (GlycoA+) precursor BM cells, and increased proportion of apoptotic cells within the CD34+/CD71+ and CD36+/GlycoA+ compartments. Burst-forming units erythroid (BFU-Es) in BM mononuclear or purified CD34+ cells were significantly reduced in the patients. Patient BFU-Es increased significantly following in vitro treatment with tumor necrosis factor-α (TNF-α) and/or interferon γ (IFN-γ)-neutralizing antibodies. Local TNF-α and IFN-γ production was higher in anemic than in nonanemic patients. EPO production was appropriate in the patients, but EPOR expression was significantly reduced in patient GlycoA+ cells, especially in anemic patients. Conclusion: Impaired BM erythropoiesis in CIN patients is probably the result of increased local production of TNF-α and IFN-γ that induce apoptosis, cell growth inhibition, and downregulation of EPOR expression on erythroid cells. We suggest that anemia in CIN patients displays overlapping pathophysiologic features with anemia of chronic disease. [Copyright &y& Elsevier]

We describe two patients with multiple myeloma (MM) involving the central nervous system (CNS). In both patients, CNS involvement was manifested with extremely rare signs and symptoms. The first patient, a 64-year-old woman, developed obstructive hydrocephalus 10 years after the initial diagnosis of MM. The disease has been successfully treated with intrathecal chemotherapy, radiotherapy and systemic chemotherapy. The other patient, a 65-year-old man, developed hypopituitarism and diabetes insipidus 1 year after MM diagnosis. Disease in this patient proved resistant to both radiotherapy and chemotherapy; the patient died 2 years later. These rare complications add new information on the wide spectrum of clinical and laboratory manifestations of MM. It is obvious that descriptions of additional cases are required to better understand the mechanisms of CNS involvement in MM patients. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs) are perivascular multipotent stem cells originally identified in the bone marrow (BM) stroma and subsequently in virtually all vascularized tissues. Because of their ability to differentiate into various mesodermal lineages, their trophic properties, homing capacity, and immunomodulatory functions, MSCs have emerged as attractive candidates in tissue repair and treatment of autoimmune disorders. Accumulating evidence suggests that the beneficial effects of MSCs may be primarily mediated via a number of paracrine-acting soluble factors and extracellular vesicles (EVs). EVs are membrane-coated vesicles that are increasingly being acknowledged as playing a key role in intercellular communication via their capacity to carry and deliver their cargo, consisting of proteins, nucleic acids, and lipids to recipient cells. MSC-EVs recapitulate the functions of the cells they originate, including immunoregulatory effects but do not seem to be associated with the limitations and concerns of cell-based therapies, thereby emerging as an appealing alternative therapeutic option in immune-mediated disorders. In the present review, the biology of MSCs will be outlined and an overview of their immunomodulatory functions will be provided. In addition, current knowledge on the features of MSC-EVs and their immunoregulatory potential will be summarized. Finally, therapeutic applications of MSCs and MSC-EVs in autoimmune disorders will be discussed. [ABSTRACT FROM AUTHOR]