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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]

Purposes: To (i) determine expression patterns of lysyl oxidase-like 1 (LOXL1), fibrillin-1 (FBN1), transforming growth factor beta-1 (TGF-β1), and cyclooxygenase-2 (COX-2) in lens epithelium and anterior lens capsule in pseudoexfoliation (PEX) syndrome and (ii) delineate the roles of these proteins in the etiopathogenesis of PEX. Materials and methods: Study participants, all of whom had undergone cataract surgery, comprised 47 patients with and 27 patients without (controls) PEX syndrome. Immunohistochemistry on paraffin sections of lens capsule and lens epithelium was performed. Results: Immunoexpression of LOXL1 and FBN1 on the outer surface of the lens capsule was significantly higher (p < 0.001), and nuclear immunopositivity for LOXL1 was more frequently observed (p = 0.017), in PEX patients compared with control patients. Cytoplasmic expression of LOXL1 and COX-2 was significantly lower (p = 0.015 and p = 0.042, respectively) in PEX patients compared with controls. TGF-β1 exhibited diffuse immunostaining detected in all cell layers in PEX patients (p <0.001). Significant direct correlations of cytoplasmic LOXL1 with FBN1 and TGF-β1, and of COX-2 with FBN1, TGF-β1, and LOXL-1, were observed only in PEX patients. Conclusions: Results of our study provide valuable information vis-à-vis expression and localization of TGF-β1, LOXL1, and FBN1, as well as their associations in the lens epithelium and lens capsule. These data not only advance our knowledge of the etiopathogenesis of PEX syndrome, but also include novel findings, for example, immunostaining patterns of TGF-β1 in PEX syndrome. We suggest that COX-2 plays a role in the pathobiology of PEX syndrome and should be the subject of future investigations. [ABSTRACT FROM AUTHOR]

33921711 7 Demosthenous C., Sakellari I., Douka V., Papayanni P.G., Anagnostopoulos A., Gavriilaki E. The Role of Myeloid-Derived Suppressor Cells (MDSCs) in Graft-versus-Host Disease (GVHD). Moreover, Papafragkos et al. have reviewed the current literature concerning MDSCs in lymphoid malignancies in their paper entitled " I Decoding the Myeloid-Derived Suppressor Cells in Lymphoid Malignancies i ". Another interesting field, that of the graft-versus-host disease (GVHD), is covered in the review paper of Demosthenous et al., entitled " I The Role of Myeloid-Derived Suppressor Cells (MDSCs) in Graft-versus-Host Disease (GVHD) i ". [Extracted from the article]

Increasing interest on the field of autoimmune diseases has unveiled a plethora of genetic factors that predispose to these diseases. However, in immune-mediated bone marrow failure syndromes, such as acquired aplastic anemia and chronic idiopathic neutropenia, in which the pathophysiology results from a myelosuppressive bone marrow microenvironment mainly due to the presence of activated T lymphocytes, leading to the accelerated apoptotic death of the hematopoietic stem and progenitor cells, such genetic associations have been very limited. Various alleles and haplotypes of human leucocyte antigen (HLA) molecules have been implicated in the predisposition of developing the above diseases, as well as polymorphisms of inhibitory cytokines such as interferon-γ, tumor necrosis factor-α, and transforming growth factor-β1 along with polymorphisms on molecules of the immune system including the T-bet transcription factor and signal transducers and activators of transcription. In some cases, specific polymorphisms have been implicated in the outcome of treatment on those patients. [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]

Background/Aims: Adiponectin and its receptors, AdipoR1 and AdipoR2, constitute integral components of energy homeostatic mechanism in peripheral tissues. Recent studies have implicated adiponectin in central neural networks regulating food intake and energy expenditure. The present study aimed at investigating the possible expression and distribution of adiponectin and its receptors in human pituitary gland, hypothalamus and different brain areas. Methods: Sections of the pituitary gland, hypothalamus and adjacent basal forebrain area, cerebrum and cerebellum from 35 autopsy cases, were examined using HE, PAS-Orange G, luxol fast blue/cresyl violet stains and single and double immunohistochemistry using adiponectin, AdipoR1, AdipoR2, choline acetyltransferase, FSH, LH, TSH, GH, ACTH and prolactin-specific antibodies. Age and BMI mean values ± SD of the autopsy cases were 56 ± 18 years and 27 ± 5 kg/m2, respectively. Results: Strong adiponectin expression was observed in pituitary gland. In pars distalis (PD), adiponectin localized in GH, FSH, LH and TSH-producing cells and in pars tuberalis (PT) in FSH, LH and TSH-producing cells. Strong to moderate expression of AdipoR1 and AdipoR2 was observed in PD by the same cell types as adiponectin. No immunoreactivity for adiponectin receptors was noted in cells of PT. Intense AdipoR1 immunostaining was observed in neurons of lateral hypothalamic area and of nucleus basalis of Meynert (NBM). Conclusions: Adiponectin and its receptors expression in human pituitary might indicate the existence of a local system, modulating endocrine axes. Furthermore, the presence of AdipoR1 in hypothalamus and NBM suggests that adiponectin may participate in central neural signaling pathways controlling energy homeostasis and higher brain functions. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The levels of soluble c-kit ligand (sKL), also known as Steel factor or stem cell factor, were measured in blood serum and long-term bone marrow culture supernatants of 81 patients with chronic idiopathic neutropenia (CIN) and 22 normal controls using a commercially available enzyme-linked immunosorbent assay (ELISA). We found that the levels of serum and culture supernatant sKL did not differ significantly between patients and control subjects and that both serum and supernatant values of the cytokine did not correlate with the number of circulating neutrophils. Furthermore, we found that the levels of the culture supernatant granulocyte colony-stimulating factor (G-CSF), also measured by ELISA, were significantly increased in the patients compared to controls but individual G-CSF values did not correlate with the values of supernatant sKL. These findings suggest that sKL-producing cells continuously secrete sKL and that cytokine secretion is independent of the degree of neutropenia or the levels of supernatant G-CSF in patients with CIN. [ABSTRACT FROM AUTHOR]

The prevalence ofHelicobacter pyloriinfection was evaluated in 120 patients with chronic idiopathic neutropenia (CIN), 8 patients with monoclonal gammopathy of undetermined significance (MGUS) associated with CIN, and 74 age- and sex-matched normal volunteers, all derived from the same geographical area. The purpose of the study was to investigate the possible causal relationships ofH. pyloriinfection with the development of MGUS in CIN patients. We found that the prevalence ofH. pyloriinfection was elevated to 69.2% in the group of CIN patients, 100% in the group of patients with CIN-associated MGUS, and 32.4% in the group of control subjects. No statistically significant difference, however, was found in the prevalence ofH. pyloriinfection between CIN patients with concomitant MGUS and CIN patients without MGUS, no resolution of the gammopathy after eradication of the bacterium, no significant rise in the titers of serum anti-H. pyloriantibodies, and no formation of an abnormal precipitation line in immunoelectrophoresis using a saline extract of NCTC11367H. pylorireference strain as antigen. We concluded that there is no evidence thatH. pyloriinfection is the cause of MGUS in CIN patients. [ABSTRACT FROM AUTHOR]

Background: Tpl2/Cot oncogene has been identified in murine T-cell lymphomas as a target of MoMuLV insertion. Animal and tissue culture studies have shown that Tpl2/Cot is involved in interleukin-2 (IL-2) and tumor necrosis factor-α (TNF-α) production by T-cells contributing to T-cell proliferation. In the present report we examined a series of 12 adult patients with various T-cell malignancies, all with predominant leukemic expression in the periphery, for the expression of Tpl2/Cot oncogene in order to determine a possible involvement of Tpl2/Cot in the pathogenesis of these neoplasms. Results: Our results showed that Tpl2/Cot was overexpressed in all four patients with Large Granular Lymphocyte proliferative disorders (LGL-PDs) but in none of the remaining eight patients with other T-cell neoplasias. Interestingly, three of the LGL-PD patients displayed neutropenia, one in association with sarcoidosis. Serum TNF-α levels were increased in all Tpl2/Cot overexpressing patients while serum IL-2 was undetectable in all subjects studied. Genomic DNA analysis revealed no DNA amplification at the Tpl2/Cot locus in any of the samples analyzed. Conclusions: We conclude that Tpl2/Cot, a gene extensively studied in animal and tissue culture T-cell models may be also involved in the development of human LGL-PD and may have a role in the pathogenesis of immune manifestations associated with these diseases. This is the first report implicating Tpl2/Cot in human T-cell neoplasias and provides a novel molecular event in the development of LGL-PDs. [ABSTRACT FROM AUTHOR]

There is an increasing evidence that the trafficking and homing of autoreactive lymphocytes in the bone marrow (BM) of patients with systemic lupus erythematosus (SLE) may affect the haemopoiesis supporting capacity of BM stroma and may also damage haemopoiesis even at the level of the haemopoietic stem cell not only via direct immune destruction but also by an indirect effect due to the release of pro-inflammatory cytokines rendering stem cells sensitive to Fas-induced apoptosis. We have shown that the low BM CD34[SUP+] cell number in SLE is due to--at least in part--Fas up-regulation on these cells and subsequent apoptotic cell death induced by interferon-γ- and Fas ligand- producing T-cells in the BM microenvironment. In accordance to previous reports demonstrating that co-culture of T-cells from SLE patients with autologous or allogeneic BM mononuclear cells may inhibit their clonogenic potential while removal of T-cells from patient BM samples may improve the in vitro colony formation, we have shown that intensive immunoablation followed by autologous stem cell rescue may restore the number and survival characteristics of BM CD34[SUP+] cells and the haemopoiesis supporting capacity of marrow stromal cells in these patients. The consideration of the complex interactions between autoreactive lymphocytes and haemopoietic progenitor cells in the BM may elucidate further the pathogenetic mechanisms underlying cytopenias in SLE and may provide an explanation for the difficulties in the stem cell collection procedure seen in SLE patients undergoing autologous stem cell transplantation. [ABSTRACT FROM AUTHOR]

Examines the effectiveness of autologous hemopoietic stem cell transplantation in treating resistant autoimmune cytopenias (AIC) disorders. Characterization of refractory autoimmune cytopenias (AIC); Pathogenesis of AIC; Properties of stem cell transplantation.

Abstract: Objective: To investigate further the cellular defect responsible for impaired granulopoiesis in severe congenital neutropenia (SCN), we have evaluated bone marrow (BM) stem cell reserve and function and BM stromal cell myelopoiesis supporting capacity in two patients with SCN. Methods: BM primitive stem cells and myeloid progenitor cells were assessed using flow cytometry, limiting dilution assay, clonogenic assays, and long-term BM cultures (LTBMC). BM stroma function was assessed by evaluating the ability of irradiated stromal layers from the patients to induce granulocyte-macrophage colony formation (CFU-GM) by normal CD34+ cells. Results: Compared to the normal controls (n = 37), SCN patients displayed a low percentage of CD34+ /CD38+ cells (P < 0.05), low CFU-GM colony formation by highly purified CD34+ cells (P < 0.05), low CFU-GM recovery in LTBMC (P < 0.05), and normal primitive stem cells as indicated by the frequency of CD34+ /CD38– cells and the number of long-term culture initiating cells. Patient BM stromal layers exhibited normal myelopoiesis supporting capacity as shown by the CFU-GM content of irradiated LTBMC recharged with normal CD34+ cells. In addition, patient LTBMC supernatants displayed 20-fold normal granulocyte colony stimulating factor and 2-fold normal granulocyte-macrophage colony stimulating factor levels. Conclusion: These data show that primitive BM stem cells and stromal cells are not affected in SCN patients, while they support further the concept of a primary defect at the myeloid progenitor cell level. To know the differentiation stage at which the underlying defect causes the malfunction will be relevant for further elucidation of its nature at the molecular level. [ABSTRACT FROM AUTHOR]

The changes in bone marrow (BM) stem cell reserve and function and stromal cell function in patients with active systemic lupus erythematosus (SLE) were investigated. The study was carried out on seven SLE patients and 28 healthy controls using flow cytometry and in vitro cell culture assays. We found that patients had low CD34+ cells, compared with the control group, reflecting the decrease of both CD34+/CD38- and CD34+/CD38+ cells. Patient CD34+/Fas+ but not CD34-/Fas+ cells were significantly increased. Apoptotic (7AADdim) cells were higher among CD34+/Fas+ than among CD34+/Fas- cells, and individual values of apoptotic CD34+ cells strongly correlated with the number of CD34+/Fas+ cells. These findings are suggestive of a Fas-mediated apoptosis accounting for the low CD34+ cells in SLE patients. Moreover, we found that patients had low numbers of granulocyte-macrophage colony-forming units (CFU-GM) and erythroid burst-forming units (BFU-E), compared with the control group, and that the generation of colony-forming cells in long-term BM cultures was significantly reduced. Patient BM stroma failed to support allogeneic progenitor cell growth. In one patient, CD34+ cells were increased, apoptotic CD34+/Fas+ cells were normalized and defective stromal cell function was restored after autologous stem cell transplantation. We concluded that defective haemopoiesis in SLE patients is probably caused, at least in part, to the presence of autoreactive lymphocytes in BM. [ABSTRACT FROM AUTHOR]

There is strong evidence that non-immune chronic idiopathic neutropenia of adult is a cytokine-mediated syndrome characterized by (a) neutropenia of varying degree associated with a low number of lineage-specific CD34+ cells and increased production of inhibitors of hematopoiesis, including transforming growth factor-β1 and tumor necrosis factor-α; (b) lymphopenia due to selective loss of primed/memory T-cells and NK cells; (c) increased splenic volume on ultrasonography in 48.1% of patients; (d) osteopenia and/or osteoporosis in 60.0% of patients; (e) anemia, mostly of the type of anemia of chronic disease, in 15.6% of patients; (f) features of chronic antigenic stimulation, including increased proportion of bone marrow plasma cells, increased serum levels of IgG1 and/or IgA, increased frequency of monoclonal gammopathy of undetermined significance, increased frequency of antinuclear antibodies with specific reactivity, and increased serum levels of circulating immune complexes; and (g) increased concentrations of a variety of macrophage-derived pro-inflammatory cytokines and chemokines capable of affecting bone metabolism, bone marrow function, and leukocyte trafficking. All these findings are suggestive of the existence of an unrecognized low-grade chronic inflammatory process which may be involved in the pathogenesis of the disorder. Neutropenia in these patients is probably the result of a combination of at least three factors, reduced neutrophil production in bone marrow, enhanced neutrophil extravasation, and increased sequestration and/or extravasation of neutrophils into the spleen. [ABSTRACT FROM AUTHOR]

This study describes the frequency of serum organ-specific and organ-nonspecific autoantibodies in 157 patients with nonimmune chronic idiopathic neutropenia of adults (NI-CINA). Forty-two age- and gender-matched volunteers were used as controls. We found that patients with NI-CINA had increased frequency of antinuclear antibodies (ANA) compared to controls (33.1 vs. 9.5%, p = 0.0025), and that ANA positivity inversely correlated with the number of circulating neutrophils (r = –0.2765, p < 0.0001). Speckled pattern of reactivity was seen in 84.6% of ANA-positive patients, and diffuse pattern in the remaining 15.4%. Patients had also increased levels of circulating immune complexes compared to controls (3.30 ± 2.41 vs. 1.70 ± 1.19 µg/ml, p = 0.0042), which inversely correlated with the number of circulating neutrophils (r = –0.2405, p = 0.0154) but not with the titer of ANA positivity. No significant differences were found between the patients and the normal controls in the frequency of positive tests for antibodies to dsDNA, Sm, nRNP, SSA, SSB and Scl-70 antigens, or for parietal cell antibodies, anti-neutrophil cytoplasmic antibodies (ANCA), anti-cardiolipin and anti-thyroid antibodies. Serum levels of rheumatoid factor, C-reactive protein (CRP) and complement factors C3 and C4 ranged within normal limits in the patients studied, but a highly significant correlation was noted between the levels of CRP and ANA positivity (r = 0.3936, p < 0.0001). These findings are suggestive of a chronic inflammation in NI-CINA patients which provides the antigenic stimulus for ANA production, and they further support our previously reported suggestion for the possible involvement of such a low-grade chronic inflammatory process in the pathogenesis of neutropenia in the affected subjects.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: To study the changes in serum immunoglobulins and some closely related pro‐inflammatory cytokines in patients with nonimmune chronic idiopathic neutropenia of adults (NI‐CINA). Methods: Serum levels of gamma‐globulins, IgG, IgA, IgM, IgG subclasses, interleukin‐4 (IL‐4), interferon‐gamma (IFN‐γ) and transforming growth factor‐beta1 (TGF‐β1) were evaluated in 83 NI‐CINA patients and 65 normal controls using the respective conventional methods. Results: We found that serum gamma‐globulin, IgG and IgG1 levels were all significantly increased in the entire group of patients studied, compared to controls (p<0.001, p<0.01 and p<0.01, respectively), while the levels of IgG3 were significantly reduced (p<0.001). Serum IgA were increased in patients with severe neutropenia (p<0.001). No significant changes were noted in serum IgM, IgG2 and IgG4 levels. The infrequent occurrence of detectable amounts of IL‐4 and IFN‐γ in the serum was similar in both, patients and control subjects. Serum levels of TGF‐β1 were increased in all groups of patients studied and they correlated inversely with the levels of IgG3 (p<0.001) and positively with the levels of IgA (p<0.001), suggesting the possible involvement of the cytokine in immunoglobulin class switching. Conclusion: Patients with NI‐CINA have significant changes in serum immunoglobulins and some inflammation‐related cytokines. These findings provide additional evidence for the existence of an unrecognized low‐grade chronic inflammatory process in NI‐CINA patients and coroborate our previously reported suggestion for the possible involvement of this inflammation in the pathogenesis of neutropenia in the affected subjects. [ABSTRACT FROM AUTHOR]

Retractile mesenteritis is an extremely rare disease characterised by a non-specific inflammatory and fibrotic process of the mesenteric adipose tissue, which is usually accompanied by pain and a variety of other abdominal symptoms. We describe here the case of a patient with retractile mesenteritis presenting with prolonged high-grade fever and autoimmune haemolytic anaemia without abdominal symptoms. The patient’s illness was complicated by chylous ascites. Diagnosis was suspected by computed tomography and confirmed histologically following exploratory laparotomy. The patient was treated with prednisone and azathioprine, and he had a rapid improvement in anaemia and fever relief, but no substantial change in the mesenteric lesions. Our case adds autoimmune haemolytic anaemia to the wide spectrum of manifestations of retractile mesenteritis and implies the possible involvement of immune mechanisms in the pathogenesis of the disease.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes (MDS) are hematopoietic malignancies characterized by the clonal expansion of hematopoietic stem cells, bone marrow failure manifested by cytopenias, and increased risk for evolving to acute myeloid leukemia. Despite the fact that the acquisition of somatic mutations is considered key for the initiation of the disease, the bone marrow microenvironment also plays significant roles in MDS by providing the right niche and even shaping the malignant clone. Aberrant immune responses are frequent in MDS and are implicated in many aspects of MDS pathogenesis. Recently, myeloid-derived suppressor cells (MDSCs) have gained attention for their possible implication in the immune dysregulation associated with MDS. Here, we summarize the key findings regarding the expansion of MDSCs in MDS, their role in MDS pathogenesis and immune dysregulation, as well their potential as a new therapeutic target for MDS. [ABSTRACT FROM AUTHOR]

A study conducted by the European Network for Innovative Diagnosis and Treatment of Chronic Neutropenias (EuNet-INNOCHRON) and other organizations examined the impact of COVID-19 on patients with chronic neutropenia (CNP). The study collected data from 57 CNP patients infected with SARS-CoV-2 between March 2020 and May 2022. The findings showed that CNP patients experienced similar symptoms to the general population, with fever, cough, and musculoskeletal pains being the most frequently reported. The study also found that isolated CNP did not increase the risk of severe COVID-19 infection unless other comorbidities were present. Patients on long-term granulocyte colony-stimulating factor (G-CSF) treatment were more likely to develop musculoskeletal symptoms and shortness of breath, but these symptoms were not severe enough to require hospitalization. The study concluded that CNP patients should be treated according to local protocols and that initiation of G-CSF treatment is generally not necessary. Further research is needed to assess the relative susceptibility of CNP patients to SARS-CoV-2. [Extracted from the article]

The levels of serum and long-term bone marrow culture supernatant soluble flt-3 ligand (sFL) were determined in 54 patients with chronic idiopathic neutropenia (CIN) and 16 normal controls. Both serum and supernatant sFL levels were significantly increased in the patients compared with controls. Individual sFL values inversely correlated with the number of circulating neutrophils and the proportion of bone marrow CD34+ cells. Supernatant sFL values positively correlated with the levels of supernatant G-CSF. These findings suggest that the impaired myelopoiesis in CIN patients is accompanied by a compensatory mechanism attempting to increase the neutrophil production at the myeloid progenitor cell level. [ABSTRACT FROM AUTHOR]

The umbilical cord blood (UCB) donated in public UCB banks is a source of hematopoietic stem cells (HSC) alternative to bone marrow for allogeneic HSC transplantation (HSCT). However, the high rejection rate of the donated units due to the strict acceptance criteria and the wide application of the haploidentical HSCT have resulted in significant limitation of the use of UCB and difficulties in the economic sustainability of the public UCB banks. There is an ongoing effort within the UCB community to optimize the use of UCB in the field of HSCT and a parallel interest in exploring the use of UCB for applications beyond HSCT i.e., in the fields of cell therapy, regenerative medicine and specialized transfusion medicine. In this report, we describe the mode of operation of the three public UCB banks in Greece as an example of an orchestrated effort to develop a viable UCB banking system by (a) prioritizing the enrichment of the national inventory by high-quality UCB units from populations with rare human leukocyte antigens (HLA), and (b) deploying novel sustainable applications of UCB beyond HSCT, through national and international collaborations. The Greek paradigm of the public UCB network may become an example for countries, particularly with high HLA heterogeneity, with public UCB banks facing sustainability difficulties and adds value to the international efforts aiming to sustainably expand the public UCB banking system. [ABSTRACT FROM AUTHOR]

Myeloid-derived suppressor cells (MDSCs) are notable innate immune cells, which are further divided into two subpopulations, i.e., monocytic and granulocytic. These cells are traditionally considered to mainly suppress the T-cell responses. However, more updated data indicate that their properties are rather immunomodulatory than solely immunosuppressive. Indeed, MDSCs display extensive crosstalk with other either innate or adaptive immune cells, and, according to the situation under which they are triggered, they may enhance or attenuate the immune response. However, their positive role in host's defense mechanisms under specific conditions is rarely discussed in the literature. In this mini-review, the authors briefly summarise the mechanisms of action of MDSCs under distinct conditions, such as infections and malignancies, with a particular emphasis on their role as components of the innate immunity system. [ABSTRACT FROM AUTHOR]

Background/Aims: Nesfatin-1, processed from nucleobindin-2 (NUCB2), is a potent anorexigenic peptide being expressed in rodent hypothalamic nuclei and involved in the regulation of feeding behavior and body weight in animals. The present study aimed to investigate NUCB2/nesfatin-1 protein expression in the human hypothalamus as well as its correlation with body weight. Methods: Sections of hypothalamus and adjacent cholinergic basal forebrain nuclei, including the nucleus basalis of Meynert (NBM) and the diagonal band of Broca (DBB), from 25 autopsy cases (17 males, 8 females; 8 lean, 9 overweight, 8 obese) were examined using immunohistochemistry and double immunofluorescence labeling. Results: Prominent NUCB2/nesfatin-1 immunoexpression was detected in supraoptic, paraventricular, and infundibular nuclei, lateral hypothalamic area (LHA)/perifornical region, and NBM/DBB. NUCB2/nesfatin-1 was found to extensively colocalize with (a) oxytocin and vasopressin in paraventricular and supraoptic nuclei, (b) melanin-concentrating hormone in the LHA, and (c) cocaine- and amphetamine-regulated transcript in infundibular and paraventricular nuclei and LHA. Interestingly, in the LHA, NUCB2/nesfatin-1 protein expression was significantly decreased in obese, compared with lean (p < 0.01) and overweight (p < 0.05) subjects. Conclusions: The findings of the present study are suggestive of a potential role for NUCB2/nesfatin-1 as an integral regulator of food intake and energy homeostasis in the human hypothalamus. In the LHA, an appetite- and reward-related brain area, reduced NUCB2/nesfatin-1 immunoexpression may contribute to dysregulation of homeostatic and/or hedonic feeding behavior and obesity. NUCB2/nesfatin-1 localization in NBM/DBB might imply its participation in the neuronal circuitry controlling cognitive influences on food intake and give impetus towards unraveling additional biological actions of NUCB2/nesfatin-1 in human neuronal networks. [ABSTRACT FROM AUTHOR]

Background: Tumor infiltrating lymphocytes (TILs) represent important regulators of carcinogenesis. Cutaneous invasive squamous cell carcinoma (inSCC) develops through precursor lesions, namely in situ squamous cell carcinoma (isSCC) and actinic keratosis (AK), representing a natural model of carcinogenesis. The study evaluates TIL subpopulations in inSCC and its precursors by comparing 2 semiquantitative scoring systems, and assesses the presence of regulatory T‐cells (Tregs) in these lesions. Methods: Paraffin sections from 33 cases of AK, 19 isSCCs and 34 inSCCs with adjacent precursor lesions or normal skin (NS) were immunostained for CD3, CD4, CD8 and Foxp3. TIL subgroups were evaluated by the semiquantitative Klintrup‐Mäkinen (K‐M) score, and by a more detailed modification of this system. Treg counts were assessed by image analysis quantification. Results: An increase of all TIL subpolulations from precursor lesions toward inSCC was shown by both scoring systems. Treg counts progressively increased from NS to AK and isSCC, but decreased in inSCC. Tregs were more numerous in pT2 and around indolent inSCCs compared to T1 and aggressive subtypes. Conclusions: T‐cells and cytotoxic T‐cells progressively increase in cutaneous squamous cell carcinogenesis, while Treg counts diminish in inSCC. The K‐M score is an appropriate, easily applicable TIL scoring system in cutaneous inSCC. [ABSTRACT FROM AUTHOR]

A 63-year-old Caucasian man presented with a 4- month history of disseminated asymptomatic reddish- brown papulonodular lesions. A skin biopsy showed dermal infiltration with CD68+ histiocytes, predominantly with eosinophilic cytoplasm, some with a ground-glass cytoplasm, and a small number of giant cells. The diagnosis of multiple cutaneous reticulohistiocytosis was made. Bone marrow immunophenotyping due to peripheral blood lymphocytosis revealed the presence of a monoclonal population of CD3+, CD8+ CD57+ large granular lymphocytes. The present case suggests the coexistence of multiple cutaneous reticulohistiocytosis with an underlying disorder. [ABSTRACT FROM AUTHOR]

Introduction: Aberrant activation of endothelin (ET) axis has been identified as a key player in tumor growth and metastasis in several tumor types. However, little is known about the possible interaction of the ET with epithelial to mesenchymal transition (EMT), a process that transforms tumor cells in a motile, resistant to apoptosis phenotype prone to invasion and metastasis. The aim of this study was to investigate the activation of the ET axis in prostate adenocarcinoma and examine possible associations with EMT markers, lymph node (LN) metastasis, and other clinicopathological parameters. Materials and Methods: We immunohistochemically evaluated the expression of ET-1 and its receptors A and B (ET-A, ET-B) in 64 N0 and 23 N1 prostate adenocarcinoma cases. EMT markers E-cadherin, N-cadherin, and β-catenin and the transcriptional factor SNAIL were evaluated. We examined possible correlations of ET pathway members with EMT markers, LN status, Gleason grade, and T stage. Results: Our results revealed increased expression of ET-1 and ET-A (but not ET-B) in prostate carcinoma; both ET-1 and ET-A were associated with lymph metastasis and T stage but not with Gleason grade. We observed E-cadherin and β-catenin decrease/relocalization and increased N-cadherin expression. SNAIL also showed increased expression in tumor tissue and was associated with LN metastasis (Mann-Whitney test, P = 0.0032). Expression of ET-1 and ET-A correlated well with SNAIL expression (Spearman r, P = 0.0002 and P = 0.0176, respectively). Conclusions: These findings indicate that activation of the ET pathway may induce EMT through SNAIL activation and correlates with increased metastatic potential. [ABSTRACT FROM AUTHOR]

Objective Romiplostim has maintained long-term platelet counts in patients with immune thrombocytopenia ( ITP) for up to 5 yr in clinical studies. This prospective observational study aimed to describe romiplostim utilisation and outcomes in European clinical practice. Methods Adults with primary ITP who received romiplostim in routine care were eligible. Results Three-hundred and forty patients were eligible for analysis, of whom 299 (88%) completed the 2-yr observation period. The median age was 62 yr, with 43% of patients aged ≥65 yr, and two-thirds of patients initiated romiplostim before splenectomy. The median average weekly dose of romiplostim was 2.8 μg/kg. The median baseline platelet count was 20 × 109/L, which increased after 2 wk of romiplostim treatment and remained >50 × 109/L thereafter. After romiplostim initiation, there was a decrease in rates of grade ≥3 bleeding events (from 12 to 2 per 100 patient-years) and ITP-related hospitalisations (from 87 to 33 per 100 patient-years). The rate of thrombotic events was 2 per 100 patient-years, and bone marrow fibrosis occurred in two patients. Conclusions Romiplostim dosing, effectiveness and safety in an unselected real-world ITP population seemed comparable with that observed in clinical studies. [ABSTRACT FROM AUTHOR]

Data on animals emphasize the importance of the neuronal glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) for feeding suppression, although it is unclear whether astrocytes participate in the transduction of anorectic GLP-1R-dependent signals. In humans, the brain circuitry underlying these effects remains insufficiently investigated. The present study aimed to explore GLP-1R protein expression in the human hypothalamus and its correlation with body mass index (BMI). Sections of hypothalamus from 28 autopsy cases, 11 with normal weight (BMI < 25 kg/m2) and 17 with non-normal weight (BMI ≥ 25 kg/m2), were examined using immunohistochemistry and double immunofluorescence labeling. Prominent GLP-1R immunoexpression was detected in neurons of several hypothalamic nuclei, including paraventricular, supraoptic, and infundibular nuclei; the lateral hypothalamic area (LH); and basal forebrain nuclei. Interestingly, in the LH, GLP-1R was significantly decreased in individuals with BMI ≥ 25 kg/m2 compared with their normal weight counterparts (p = 0.03). Furthermore, GLP-1R was negatively correlated (τb = −0.347, p = 0.024) with BMI levels only in the LH. GLP-1R extensively colocalized with the anorexigenic and antiobesogenic neuropeptide nucleobindin-2/nesfatin-1 but not with the astrocytic marker glial fibrillary acidic protein. These data suggest a potential role for GLP-1R in the regulation of energy balance in the human hypothalamus. In the LH, an appetite- and reward-related brain region, reduced GLP-1R immunoexpression may contribute to the dysregulation of homeostatic and/or hedonic feeding behavior. Possible effects of NUCB2/nesfatin-1 on central GLP-1R signaling require further investigation. [ABSTRACT FROM AUTHOR]

Presents the case of an adult woman with severe neutropenia and recurrent respiratory infections. Results of the physical examination; Presence of sea-blue histiocytes occurring either in dispersed or small aggregates; Measurement of the granulocyte colony-stimulating factor levels.

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]

Background: Genomic instability is a common feature in hepatocellular carcinoma. Deregulation of replication licensing factors has been shown to trigger DNA damage response contributing to genomic instability. Overexpression of DNA replication licensing factors chromatin licensing and DNA replication factor 1 (CDT1) and minichromosome maintenance complex component 7 (MCM7) has been previously reported in several human cancers. The aim of the present study was to evaluate the expression and prognostic significance of CDT1 and MCM7 in association with DNA damage response markers and p53 in patients with hepatocellular carcinoma.Methods: Expression of CDT1, MCM7, p-H2A histone family member X (H2AX), phospho-ataxia telangiectasia-mutated (ATM)/ataxia telangiectasia rad3-related (ATR) substrate, and p53 was evaluated by immunohistochemistry on formalin-fixed paraffin-embedded surgical specimens from 111 patients who underwent hepatectomy for hepatocellular carcinoma. Statistical analysis was performed to evaluate associations between the studied proteins, clinicopathological parameters, and patient survival.Results: CDT1 expression correlated with p-H2AX (p = 0.038), while MCM7 correlated with p-H2AX and phospho-ATM/ATR substrate (p < 0.001). Increased CDT1 expression was associated with higher tumor grade (p = 0.006) and tumor-node-metastasis (TNM) stage (p = 0.033). High CDT1 expression correlated significantly with reduced overall survival (60.8 and 26.5 % vs 82.8 and 53.0 %, for low CDT1 expression, at 2 and 5 years, respectively, p = 0.012) and was identified by multivariate analysis as an independent predictor of poor overall survival (p = 0.049).Conclusions: Overexpression of CDT1 and MCM7 in hepatocellular carcinoma correlates with DNA damage response, and CDT1 overexpression is a significant prognostic biomarker in hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Chronic neutropenia (CN) corresponds with absolute count of neutrophils below 1.8 × 109/L in last three months. Besides, neutropenia that persists more than three months and in absence of underlying diseases, chemical components, irradiation, use of particular drugs, inflammation, is defined as chronic idiopathic neutropenia (CIN). There are three types of CN - severe, moderate and mild, with or without extra-hematopoietic manifestations. The aim of this report was to define a stratified approach toward patient with hypothesis of CIN, including timely patient recognition with consequent follow-up and actions afterwards based on recommendation from EuNet INNOCHRON-European Network for Innovative Diagnosis and Treatment of Chronic Neutropenias. Case presented a 40-year-old female who went to the Hematology Department of the University Clinical Center Niš for regular health condition and blood count control. Since she was 21, she has been monitoring neutropenia, which occurred immediately after first child birth. Laboratory parameters and peripheral blood smear values were within physiological range. Performed immune assays excluded the immune background of neutropenia. In the next step, we excluded viral infections as a cause of neutropenia with particular serological tests. Also, a bone marrow aspiration was performed with results in physiological range. Chronic neutropenia can be associated with serious health complications. The Severe Chronic Neutropenia International Registry (SCNIR) is a global organization dedicated to finding the causes, consequences and best treatments for severe CN. Similar to other European countries, we suggest the introduction of defined approach to diagnosis, registration and monitoring of chronic neutropenia patients in Serbia through Register. [ABSTRACT FROM AUTHOR]

The high genetic diversity of HLA across populations significantly confines the effectiveness of a donor or umbilical cord blood search for allogeneic hematopoietic stem cell transplantation (HSCT). This study aims to probe the HLA immunogenetic profile of the population of Crete, a Greek region with specific geographic and historical characteristics, and to investigate potential patterns in HLA distribution following comparison with the Deutsche Knochenmarkspenderdatei (DKMS) donor registry. It also aims to highlight the importance of regional public cord blood banks (PCBBs) in fulfilling HSCT needs, especially in countries with significant genetic diversity. A cohort of 1835 samples representative of the Cretan population was typed for HLA class I (HLA-A, HLA-B, HLA-C) and class II (HLA-DRB1, HLA-DQB1, HLA-DPB1) loci by high-resolution second field next-generation sequencing. Data were compared with the respective HLA profiles of 12 DKMS populations (n = 20 032). Advanced statistical and bioinformatics methods were employed to assess specific intra- and inter-population genetic indexes associated with the regional and geographic distribution of HLA alleles and haplotypes. A considerable HLA allelic and haplotypic diversity was identified among the Cretan samples and between the latter and the pooled DKMS cohort. Even though the HLA allele and haplotype frequency distribution was similar to regions of close geographic proximity to Crete, a clinal distribution pattern from the northern to southern regions was identified. Significant differences were also observed between Crete and the Greek population of DKMS. This study provides an in-depth characterization of the HLA immunogenetic profile in Crete and reveals the importance of demographic history in HLA heterogeneity and donor selection. The novel HLA allele and haplotype frequency comparative data between the Cretan and other European populations signify the importance of regional PCBBs in prioritizing HLA diversity to efficiently promote the HSCT program at the national level and beyond. [ABSTRACT FROM AUTHOR]

In a recent review from the SCNIR European and North-American Branches, based on 650 patients with severe congenital neutropenia, I GFI1 i was recognized as a rare pathogenetic gene accounting for less than 6% of patients [[5]]. Since the first description of the pathogenic I GFI1 i germline variants in four patients with neutropenia and monocytosis, only rare cases of I GFI1 i -related neutropenias have been reported [[8]-[10]]. Dear Editor, Chronic neutropenia, defined as an absolute neutrophil count (ANC) < 1.8 × 10 SP 9 sp /L for more than 3 months, is a common cause of referral to adult hematologists [[1]]. [Extracted from the article]

Background: The TGF-β signaling repressors SnoN and Ski have been critically implicated in human cancer. Methods: To explore the role of SnoN and Ski in the development and progression of colorectal cancer we examined their protein expression profile by immunohistochemistry in a series of human colorectal adenomas, carcinomas and lymph node metastases. The mRNA expression of SnoN was also quantified by Real-Time RT-PCR. Results: SnoN and Ski were overexpressed both in adenomas with severe dysplasia and colorectal carcinomas. Protein expression was cytoplasmic and nuclear with predominant cytoplasmic localization. The subcellular localization was related differently to pathologic variables of colorectal carcinomas. Although there was no significant association of protein levels with tumor invasion and metastasis, a significant correlation of nuclear SnoN and Ski with β-catenin pathway was observed. Moreover, SnoN mRNA did not differ in carcinomas as compared to normal control and there was no correlation between SnoN protein and mRNA levels. Conclusion: Our findings suggest that SnoN and Ski exert oncogenic effects in human colorectal carcinogenesis and their overexpression is implicated in early stage disease. [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]

Dear Editor, Severe congenital neutropenia (SCN) is a heterogeneous group of rare inherited bone marrow failure syndromes characterized by absolute neutrophil count (ANC) lower than 0.5 × 10 SP 9 sp /L, increased susceptibility to bacterial infections, and high propensity to leukemic transformation [[1]]. Manifestations from the digestive system have been rarely reported in I G6PC3- i SCN patients and include inflammatory bowel disease (IBD), most closely resembling Crohn's disease, and IBD-like chronic inflammation of the large bowel [[7]]. [Extracted from the article]

Background: Genomic instability is a hallmark of cancer cells contributing to tumor development and progression. Integrin-linked kinase (ILK) is a focal adhesion protein with well-established role in carcinogenesis. We have previously shown that ILK overexpression is critically implicated in human colorectal cancer (CRC) progression. In light of the recent findings that ILK regulates centrosomes and mitotic spindle formation, we aimed to determine its implication in mechanisms of genomic instability in human CRC.Methods: Association of ILK expression with markers of genomic instability (micronuclei formation, nucleus size, and intensity) was investigated in diploid human colon cancer cells HCT116 upon ectopic ILK overexpression, by immunofluorescence and in human CRC samples by Feulgen staining. We also evaluated the role of ILK in mitotic spindle formation, by immunofluorescence, in HCT116 cells upon inhibition and overexpression of ILK. Finally, we evaluated association of ILK overexpression with markers of DNA damage (p-H2AX, p-ATM/ATR) in human CRC tissue samples by immunohistochemistry and in ILK-overexpressing cells by immunofluorescence.Results: We showed that ILK overexpression is associated with genomic instability markers in human colon cancer cells and tissues samples. Aberrant mitotic spindles were observed in cells treated with specific ILK inhibitor (QLT0267), while ILK-overexpressing cells failed to undergo nocodazole-induced mitotic arrest. ILK overexpression was also associated with markers of DNA damage in HCT116 cells and human CRC tissue samples.Conclusions: The above findings indicate that overexpression of ILK is implicated in mechanisms of genomic instability in CRC suggesting a novel role of this protein in cancer. [ABSTRACT FROM AUTHOR]

Characterization of two novel HLA‐A alleles in two Greek individuals of Cretan origin. [ABSTRACT FROM AUTHOR]

Characterization of the novel HLA‐DRB1*04:311 and HLA‐DRB1*11:277 alleles in two Greek individuals of Cretan origin. [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]

Feeding is a complex behaviour entailing elaborate interactions between forebrain, hypothalamic and brainstem neuronal circuits via multiple orexigenic and anorexigenic neuropeptides. Nucleobindin‐2 (NUCB2)/nesfatin‐1 is a negative regulator of food intake and body weight with a widespread distribution in rodent brainstem nuclei. However, its localisation pattern in the human brainstem is unknown. The present study aimed to explore NUCB2/nesfatin‐1 immunoexpression in human brainstem nuclei and its possible correlation with body weight. Sections of human brainstem from 20 autopsy cases (13 males, seven females; eight normal weight, six overweight, six obese) were examined using immunohistochemistry and double immunofluorescence labelling. Strong immunoreactivity for NUCB2/nesfatin‐1 was displayed in various brainstem areas, including the locus coeruleus, medial and lateral parabrachial nuclei, pontine nuclei, raphe nuclei, nucleus of the solitary tract, dorsal motor nucleus of vagus (10N), area postrema, hypoglossal nucleus, reticular formation, inferior olive, cuneate nucleus, and spinal trigeminal nucleus. NUCB2/nesfatin‐1 was shown to extensively colocalise with neuropeptide Y and cocaine‐ and amphetamine‐regulated transcript in the locus coeruleus, dorsal raphe nucleus and solitary tract. Interestingly, in the examined cases, NUCB2/nesfatin‐1 protein expression was lower in obese than normal weight subjects in the solitary tract (P = 0.020). The findings of the present study provide neuroanatomical support for a role for NUCB2/nesfatin‐1 in feeding behaviour and energy balance. The widespread distribution of NUCB2/nesfatin‐1 in the human brainstem nuclei may be indicative of its pleiotropic effects on autonomic, neuroendocrine and behavioural processes. In the solitary tract, a key integrator of energy status, altered neurochemistry may contribute to obesity. Further research is necessary to decipher human brainstem energy homeostasis circuitry, which, despite its importance, remains inadequately characterised. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma (LADC) is the leading cause of cancer death worldwide. Nevertheless, syngeneic mouse models of the disease are sparse, and cell lines suitable for transplantable and immunocompetent mouse models of LADC remain unmet needs. We established multiple mouse LADC cell lines by repeatedly exposing two mouse strains (FVB, Balb/c) to the tobacco carcinogens urethane or diethylnitrosamine and by culturing out the resulting lung tumours for prolonged periods of time. Characterization of the resulting cell lines (n = 7) showed that they were immortal and phenotypically stable in vitro , and oncogenic, metastatic and lethal in vivo. The primary tumours that gave rise to the cell lines, as well as secondary tumours generated by transplantation of the cell lines, displayed typical LADC features, such as glandular architecture and mucin and thyroid transcription factor 1 expression. Moreover, these cells exhibited marked molecular similarity with human smokers' LADC, including carcinogen-specific Kras point mutations (Kras Q61R in urethane- and Kras Q61H in diethylnitrosamine-triggered cell lines) and Trp53 deletions and displayed stemness features. Interestingly, all cell lines overexpressed proliferin, a murine prolactin orthologue, which functioned as a lung tumour promoter. Furthermore, prolactin was overexpressed and portended poor prognosis in human LADC. In conclusion, we report the first LADC cell lines derived from mice exposed to tobacco carcinogens. These cells closely resemble human LADC and provide a valuable tool for the functional investigation of the pathobiology of the disease. [ABSTRACT FROM AUTHOR]

Characterization of the HLA‐B*51:232:02 allele in a Greek individual of Cretan origin. [ABSTRACT FROM AUTHOR]

Characterization of the novel HLA‐C*15:228 and HLA‐C*04:434 alleles in two Greek individuals of Cretan origin. [ABSTRACT FROM AUTHOR]

Hypomethylating agents are widely used in chronic myelomonocytic leukemia (CMML). We analyzed the characteristics of 88 patients with CMML homogeneously treated with 5-azacytidine (Hellenic 5-Azacytidine Registry). The overall response rate was 48.9% and the median overall survival (OS) 29.7 months. Out of the seven most widely used prognostic scoring systems for CMML, the Dusseldorf score (DUSS) showed the best prognostic capability (HR, 2.27; p <.001). Forty-one (48.8%) patients progressed to acute myeloid leukemia (AML) after a median time of 15.2 months following treatment initiation. High serum ferritin levels at diagnosis were independently correlated with low OS (HR, 2.84; p =.022), as were circulating blasts (HR, 3.47; p =.014), while a platelet count <100 × 109/L was marginally predictive of lower OS (HR, 1.45; p =.06). We selected these three factors to create a new risk stratification system for CMML with three risk groups. Finally, we highlighted for the first time the prognostic significance of serum ferritin levels in CMML. [ABSTRACT FROM AUTHOR]

Introduction: Invasive candidiasis (IC) can be a life-threatening infection in immunocompromised patients, particularly those with cancer, hematologic diseases and/or hematopoietic stem cell transplantation (HSCT) recipients. The objective of this study was to evaluate the effectiveness of micafungin in patients with hematologic malignancies or HSCT recipients, relevant to clinical presentation of IC, in real-life practice in Greece. Methods: ASPIRE was a phase IV, multicenter, non-interventional, prospective cohort study, conducted at ten tertiary hospitals in Greece, in adults with hematologic disease. Micafungin treatment for IC or prophylaxis for Candida infection was administered per standard clinical practice until a clinical outcome (success or failure) was reached. Treatment success was defined by the EORTC/MSG criteria for invasive fungal infections (IFI) and was assessed by the investigator. Treatment discontinuation and safety were also evaluated. Results: One hundred forty-three patients were enrolled. Median age was 62; 85 (59.4%) patients were male, and 133 (93.0%) had Greek ethnicity. One hundred twenty-six (88.1%) patients had hematologic malignancies, and 21 (14.7%) had received HSCT. Prophylaxis was administered to 74 (51.7%) patients [median (range) dose: 50 (50–150) mg/day] with no signs of IFI. Overall, 52 (36.4%) patients with possible IFI at baseline received micafungin treatment [100 (50–125) mg/day] versus 12 (17.2%) with probable [100 (75–150) mg/day] and 5 (3.5%) with confirmed [125 (100–150) mg/day] IFI. Treatment success was 91.6% (95% CI 85.80–95.59; n = 131) overall and 90.5% (n = 67) in patients receiving prophylaxis. Median time on treatment was 13 days. Treatment discontinuation (n = 26; 18.2%) was not related to adverse events. No treatment-related serious adverse events were reported. Conclusion: Micafungin treatment for IC or prophylaxis for Candida infection was effective and well tolerated in patients with hematologic disorders in clinical practice in Greece. These results demonstrate that micafungin could be used more widely for prophylaxis. Further work is required to determine the efficacy and safety of micafungin for the management of IFIs in hematologic settings. Funding: Astellas Pharma Inc. [ABSTRACT FROM AUTHOR]

In patients with myelodysplastic syndrome (MDS), the prognostic significance of chromosome 17 abnormalities has not yet been fully elucidated, except for isochromosome 17q that has been characterized as an intermediate risk abnormality in the Revised International Prognostic Scoring System (IPSS‐R). To further characterize the prognostic significance of chromosome 17 abnormalities we analyzed the hematologic and prognostic characteristics of 548 adult patients with MDS treated with 5‐azacytidine through the Hellenic 5‐azacytidine registry and found 32 patients with a chromosome 17 abnormality (6 with i[17q], 15 with ‐17, 3 with add[17p] and the rest with other rarer abnormalities, mostly translocations). The presence of a chromosome 17 abnormality was correlated with poor prognostic features (high IPSS, IPSS‐R, and WPSS scores) and a low overall survival rate (15.7 vs 36.4 months for patients without chromosome 17 abnormalities, Kaplan–Meier, Log Rank P < 0.00001), but these results were confounded by the fact that most (92.3%) of the cases with a chromosome 17 abnormality (with the exception of i(17q) that was found in all cases as an isolated abnormality) were found in the context of a complex karyotype. Nevertheless, one should not ignore the contribution of chromosome 17 abnormalities to the prognostic significance of a complex karyotype since 33.8% of complex karyotypes encompassed a chromosome 17 abnormality.To characterize the prognostic significance of chromosome 17 abnormalities we analyzed the hematologic and prognostic characteristics of 548 adult patients with MDS treated with 5‐azacytidine through the Hellenic 5‐azacytidine registry. The presence of a chromosome 17 abnormality (found in 32 patients) was correlated with poor prognostic features and a low overall survival rate. Although these results were confounded by the fact that most cases with a chromosome 17 abnormality were found in the context of a complex karyotype, one should not ignore the contribution of chromosome 17 abnormalities to the prognostic significance of a complex karyotype. [ABSTRACT FROM AUTHOR]