Inclusion Body Myositis and Neoplasia: A Narrative Review.

Inclusion body myositis (IBM) is an acquired, late-onset inflammatory myopathy, with both inflammatory and degenerative pathogenesis. Although idiopathic inflammatory myopathies may be associated with malignancies, IBM is generally not considered paraneoplastic. Many studies of malignancy in inflammatory myopathies did not include IBM patients. Indeed, IBM is often diagnosed only after around 5 years from onset, while paraneoplastic myositis is generally defined as the co-occurrence of malignancy and myopathy within 1 to 3 years of each other. Nevertheless, a significant association with large granular lymphocyte leukemia has been recently described in IBM, and there are reports of cancer-associated IBM. We review the pathogenic mechanisms supposed to be involved in IBM and outline the common mechanisms in IBM and malignancy, as well as the therapeutic perspectives. The terminally differentiated, CD8+ highly cytotoxic T cells expressing NK features are central in the pathogenesis of IBM and, paradoxically, play a role in some cancers as well. Interferon gamma plays a central role, mostly during the early stages of the disease. The secondary mitochondrial dysfunction, the autophagy and cell cycle dysregulation, and the crosstalk between metabolic and mitogenic pathways could be shared by IBM and cancer. There are intermingled subcellular mechanisms in IBM and neoplasia, and probably their co-existence is underestimated. The link between IBM and cancers deserves further interest, in order to search for efficient therapies in IBM and to improve muscle function, life quality, and survival in both diseases.

TERT rs2736100 A>C SNP and JAK2 46/1 haplotype significantly contribute to the occurrence of JAK2 V617F and CALR mutated myeloproliferative neoplasms - a multicentric study on 529 patients.

Polycythaemia vera (PV), essential thrombocythaemia (ET) and primary myelofibrosis (PMF) represent typical myeloproliferative neoplasms (MPN), usually characterized by specific somatic driver mutations (JAK2 V617F, CALR and MPL). JAK2 46/1 haplotype and telomerase reverse transcriptase gene (TERT) rs2736100 A>C single nucleotide polymorphism (SNP) could represent a large fraction of the genetic predisposition seen in MPN. The rs10974944 C>G SNP, tagging the JAK2 46/1 haplotype, and the TERT rs2736100 A>C SNP were genotyped in 529 MPN patients with known JAK2 V617F, CALR and MPL status, and 433 controls. JAK2 46/1 haplotype strongly correlated to JAK2 V617F-positive MPN and, to a lesser extent, CALR-positive MPN. The TERT rs2736100 A>C SNP strongly correlated to all MPN, regardless of the phenotype (PV, ET or PMF) and major molecular subtype (JAK2 V617F- or CALR-positive). While both variants have a significant contribution, they have nuanced consequences, with JAK2 46/1 predisposing essentially to JAK2 V617F-positive MPN, and TERT rs2736100 A>C having a more general, non-specific effect on all MPN, regardless of phenotype or major molecular subtype.

A Survival Analysis of Acute Myeloid Leukemia Patients Treated With Intensive Chemotherapy: A Single Center Experience.

INTRODUCTION: Acute myeloid leukaemia (AML) is a haematological disease associated with a dismal prognosis, despite major progress made in recent years in terms of antileukemic agents and supportive care. METHODS: We investigated the results of the intensive treatment of 133 fit AML patients (de novo and secondary) from a referral cancer centre in Romania, treated between January 2015 and December 2021. RESULTS: We included 79 male and 54 female patients with a median age of 53 years (range 18-70). Molecular biology analysis was available for 82.7% of patients, whereas karyotype analysis was only available for 33% of patients. The median overall survival (OS) was 8.7 months, and the disease-free survival rate was 26.3% at a median follow-up of 33.7 months. The complete remission (CR) rate after induction was 48.9% for all patients and 61.9% for patients who were assessable (excluding patients who died before being assessed for response). Twelve patients underwent allogeneic bone marrow transplantation (BMT), with the median OS not reached. Early mortality (EM), defined as death during the first 30 days after admission, was 17.3%, with the main cause of death being septic shock (78.3%). Elderly patients (≥60 years of age) had a lower OS, more primary refractory disease, and higher rates of early mortality. CONCLUSION: Complete remission rates and OS in our cohort were lower than in other reports. Early mortality was unexpectedly high, mainly due to infections, which were the main causes of death in our cohort.

Mobile Health Technology for the Personalized Therapy of Hemophilia.

The management of patients with hemophilia has evolved significantly since the first treatment attempts were made in the late 1930s. Since then, each new step in the treatment of patients with hemophilia has brought important advancements, as well as its unique set of challenges. Today, a patient-centered, individualized comprehensive approach is the new paradigm, moving away from the traditional "one size-fits-all" approach, to provide the best possible care for each patient with a bleeding disorder. As part of this complex task, mobile health applications might have the capacity to play an important role in reaching that goal. However, the use of new electronic technologies as part of a comprehensive treatment approach for patients with hemophilia simultaneously presents a new set of challenges that needs consideration. In the first section, currently available treatment of hemophilia patients will be revised, while in the second part the role of IT software in the treatment monitoring of hemophilia patients will be discussed.

The G allele of the JAK2 rs10974944 SNP, part of JAK2 46/1 haplotype, is strongly associated with JAK2 V617F-positive myeloproliferative neoplasms.

Polycythemia vera, essential thrombocythemia, and primary myelofibrosis are myeloproliferative neoplasms, characterized in a majority of cases by a unique somatic point mutation, JAK2 V617F. Recently, it was shown that JAK2 V617F occurs more frequently on a specific JAK2 haplotype, named JAK2 46/1. We genotyped 149 myeloproliferative neoplasms patients (69 had polycythemia vera, 65 had essential thrombocythemia, and 15 had primary myelofibrosis) with a known JAK2 V617F mutational status and 150 controls for the JAK2 rs10974944 (C/G) single nucleotide polymorphism, in which the G allele tags the 46/1 haplotype. We found that the rs10974944 GG/CG genotypes were significantly enriched in patients compared to controls (p < 0.0001). After stratifying for the JAK2 V617F mutational status and for the mutant allele burden, we demonstrated that GG/CG genotypes were significantly more frequent in V617F positive compared to V617F negative patients (p = 0.001), but not in V617F negative patients compared to controls (p = 0.29). Similarly, the GG/CG genotypes were significantly enriched in V617F positive patients with a mutant allele burden >50% compared to those with a mutant allele burden <50% (p = 0.0006). Our results indicate that the G allele, part of the JAK2 46/1 haplotype, contributes significantly to the occurrence of JAK2 V617F-positive myeloproliferative neoplasms. Moreover, JAK2 46/1 seems to be associated with mutant allele burden >50% in JAK2 V617F-positive myeloproliferative neoplasms patients.

Human Chorionic Gonadotropin Improves the Proliferation and Regenerative Potential of Bone Marrow Adherent Stem Cells and the Immune Tolerance of Fetal Microchimeric Stem Cells In Vitro.

Nongonadal tissues express luteinizing hormone-chorionic gonadotropin receptors (LHCG-R) which are essential for their growth during fetal development. Adult mesenchymal stem/stromal cells (MSCs) have been shown to express functional LHCG-R outside pregnancy conditions, making them susceptible to hCG stimulation. In the present study we tested the effect of hCG treatment on bone marrow (BM) derived adherent stem cells in vitro, isolated from a parous women, mother of male sons, in order to evaluate its effect on maternal MSCs and in the same time on fetal microchimeric stem cells (FMSCs), to better understand the outcomes of this safe and affordable treatment on cell proliferation and expression of pluripotency genes. Our study highlights the beneficial effects of hCG exposure on gene regulation in bone marrow adherent stem cells through the upregulation of pluripotency genes and selection of more primitive mesenchymal stem cells with a better differentiation potential. Validation of these effects on MSCs and FMSCs long after parturition in vivo represents a close perspective as it could set the premises of a new mobilization strategy for the stem cell transplantation procedures in the clinical setting.

Differential diagnosis between chronic granulocytic leukemia, polycythaemia vera and essential thrombocythemia using micro-and ultrastructural measurement data performed at the level of megakaryocyte.

The common features of chronic myeloproliferative disorders (CMDs) make the differential diagnosis on clinical or paraclinical basis to become more difficult, and validate the requirements for new methods of detailed diagnosis. Besides the cytogenetic methods, the megakaryocyte (MK) morphology is a valuable element of diagnosis included in the recent "en vogue" criteria. The purpose of this paper is to compare different morphological parameters in MKs from patients diagnosed with three CMDs and to establish a differential diagnosis of these disorders. Studies were performed on smears of bone marrow blood - for light microscope analysis -, and bone marrow biopsies - for transmission electron microscope (TEM) analysis - collected from six patients, two diagnosed with chronic granulocytic leukemia (CGL), two with polycythaemia vera (PV), and other two with essential thrombocythemia (ET). On the light microscope images, we observed important differences between the sizes of MKs and of MKs nuclei in CGL, PV, and ET. On the TEM images, we also noted important differences concerning the size and the aspect of nuclei, aspect of mitochondria, the amount and distribution of RER, Golgi apparatus and demarcation membrane system; the most important are the differences recorded in the number, distribution and sizes of vacuoles, alpha-granules and of the dense bodies. This study provides evidence that there are significant morphological differences between the cellular structures in the MKs from the patients with diagnosed with different CMDs, and thus sustains the utilization of this approach for establishing the differential diagnosis of CMDs.

Ferritin level changes and erythroid improvement in a group of adult polytransfused patients treated with Deferasirox.

BACKGROUND AND AIMS: Chelating agents therapy is recommended for polytransfused patients that have evidence of iron overload (an elevated serum ferritin or received over 20 units of red blood cell transfusions). Deferasirox showed efficacy and safety in maintaining or reducing body iron. Iron chelation therapy was associated with hematopoiesis improvement in transfusion-dependent patients.Our objectives were to analyze differences in ferritin level in adult polytransfused patients treated with Deferasirox, to estimate the erythroid improvement and variation of the number of red blood cell transfusion after introducing Deferasirox, to evaluate the side effects of the treatment. METHODS: Retrospective study including all the adult polytransfused patients treated with Deferasirox in Hematology Departments of three county hospitals in the North-West of Romania. RESULTS: We included 40 polytransfused patients treated with Deferasirox in standard doses. There was a significant reduction in serum ferritine from baseline for all the patients (Friedman test, χ2(2)=26.82, p<0.001). Safety profile of Deferasirox was good (three digestive side effects). RBCT were administered before (mean 2.43±1.09 units/month) and after starting Deferasirox (mean 1.40±0.97 units/month), the difference is statistically significant (Student Test, t(39)=6.98, p<0.001). CONCLUSIONS: Deferasirox proves to be an effective iron chelator, the serum level of ferritine decreased for all the patients during the treatment and 22.5 % of the patients developed an erythroid improvement. Safety and compliance were good.