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European Journal of Pediatrics Aug 2023Delayed cord clamping (DCC) at delivery has well-recognized benefits; however, current scientific guidelines lack uniformity in its definition. This parallel-group,... (Randomized Controlled Trial)
Randomized Controlled Trial
Delayed cord clamping (DCC) at delivery has well-recognized benefits; however, current scientific guidelines lack uniformity in its definition. This parallel-group, three-arm assessor-blinded randomized controlled trial compared the effects of three different timings of DCC at 30, 60, and 120 s on venous hematocrit and serum ferritin levels in late preterm and term neonates not requiring resuscitation. Eligible newborns (n = 204) were randomized to DCC 30 (n = 65), DCC 60 (n = 70), and DCC 120 (n = 69) groups immediately after delivery. The primary outcome variable was venous hematocrit at 24 ± 2 h. Secondary outcome variables were respiratory support, axillary temperature, vital parameters, incidences of polycythemia, neonatal hyperbilirubinemia (NNH), need and duration of phototherapy, and postpartum hemorrhage (PPH). Additionally, serum ferritin levels, the incidence of iron deficiency, exclusive breastfeeding (EBF) rate, and anthropometric parameters were assessed during post-discharge follow-up at 12 ± 2 weeks. Over one-third of the included mothers were anemic. DCC 120 was associated with a significant increase in the mean hematocrit by 2%, incidence of polycythemia, and duration of phototherapy, compared to DCC30 and DCC60; though the incidence of NNH and need for phototherapy was similar. No other serious neonatal or maternal adverse events including PPH were observed. No significant difference was documented in serum ferritin, incidences of iron deficiency, and growth parameters at 3 months even in the presence of a high EBF rate. Conclusion: The standard recommendation of DCC at 30-60 s may be considered a safe and effective intervention in the busy settings of low-middle-income countries with a high prevalence of maternal anemia. Trial registration: Clinical trial registry of India (CTRI/2021/10/037070). What is Known: • The benefits of delayed cord clamping (DCC) makes it an increasingly well-accepted practice in the delivery room. • However, uncertainty continues regarding the optimal timing of clamping; this may be of concern both in the neonate and the mother. What is New: • DCC at 120 s led to higher hematocrit, polycythemia and longer duration of phototherapy, without any difference in serum ferritin, and incidence of iron deficiency. • DCC at 30-60 s may be considered a safe and effective intervention in LMICs.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Infant, Premature; Polycythemia; Aftercare; Umbilical Cord Clamping; Patient Discharge; Anemia; Iron Deficiencies; Hyperbilirubinemia, Neonatal; Constriction; Ferritins; Umbilical Cord; Delivery, Obstetric
PubMed: 37278737
DOI: 10.1007/s00431-023-05053-6 -
Journal of the Advanced Practitioner in... Jul 2023Polycythemia vera is a Philadelphia chromosome-negative myeloproliferative neoplasm that results in increased myeloproliferation. It is a debilitating disease... (Review)
Review
Polycythemia vera is a Philadelphia chromosome-negative myeloproliferative neoplasm that results in increased myeloproliferation. It is a debilitating disease characterized by the overproduction of red blood cells, but it also can result in increased white blood cells and platelets. Patients experience a shortened overall survival due to an increased risk of thrombotic events, including stroke, myocardial infarction, pulmonary embolism, and deep vein thrombosis. Current treatment strategies in clinical practice are driven by mitigating the risk of these thrombotic events by reducing patients' hematocrit. In addition to thrombosis risk, polycythemia vera patients have constitutional symptoms such as fatigue, itching, bone pain, erythromelalgia, and splenomegaly. An increased risk of transformation of their disease to acute myeloid leukemia and/or myelofibrosis can also affect long-term survival in polycythemia vera. Additional research has identified other risk factors, such as increased white blood cells, increased platelet count, and cytokine levels, which can alter the prognosis of the disease. In this review, we will discuss the current treatment strategies in polycythemia vera and determine if incorporating additional biomarkers as endpoints is feasible in clinical practice.
PubMed: 37576360
DOI: 10.6004/jadpro.2023.14.5.5 -
Leukemia Oct 2023
Topics: Humans; Polycythemia Vera; Progression-Free Survival; Recombinant Proteins
PubMed: 37634011
DOI: 10.1038/s41375-023-02008-6 -
World Journal of Cardiology Nov 2023Myeloproliferative neoplasms (MPNs) are a heterogeneous group of hematologic malignancies characterized by an abnormal proliferation of cells of the myeloid lineage.... (Review)
Review
Myeloproliferative neoplasms (MPNs) are a heterogeneous group of hematologic malignancies characterized by an abnormal proliferation of cells of the myeloid lineage. Affected individuals are at increased risk for cardiovascular and thrombotic events. Myocardial infarction (MI) may be one of the earliest clinical manifestations of MPNs or may be a thrombotic complication that develops during the natural course of the disease. In the present review, we examine the epidemiology, pathogenesis, clinical presentation, and management of MI in MPNs based on the available literature. Moreover, we review potential biomarkers that could mediate the MI-MPNs crosstalk, from classical biochemical tests, , lactate dehydrogenase, creatine kinase and troponins, to pro-inflammatory cytokines, oxidative stress markers, and clonal hematopoiesis.
PubMed: 38058401
DOI: 10.4330/wjc.v15.i11.571 -
Faculty Reviews 2023Primary myelofibrosis (PMF), polycythemia vera (PV) and essential thrombocythemia (ET) form the classical -negative myeloproliferative neoplasms (MPNs) that are driven... (Review)
Review
Primary myelofibrosis (PMF), polycythemia vera (PV) and essential thrombocythemia (ET) form the classical -negative myeloproliferative neoplasms (MPNs) that are driven by a constitutive activation of JAK2 signaling. PMF as well as secondary MF (post-ET and post-PV MF) are the most aggressive MPNs. Presently, there is no curative treatment, except allogenic hematopoietic stem cell transplantation. JAK inhibitors, essentially ruxolitinib, are the therapy of reference for intermediate and high-risk MF. However, presently the current JAK inhibitors behave mainly as anti-inflammatory drugs, improving general symptoms and spleen size without major impact on disease progression. A better understanding of the genetics of MF, the biology of its leukemic stem cells (LSCs), the mechanisms of fibrosis and of cytopenia and the role of inflammatory cytokines has led to new approaches with the development of numerous therapeutic agents that target epigenetic regulation, telomerase, apoptosis, cell cycle, cytokines and signaling. Furthermore, the use of a new less toxic form of interferon-α has been revived, as it is presently one of the only molecules that targets the mutated clone. These new approaches have different aims: (a) to provide alternative therapy to JAK inhibition; (b) to correct cytopenia; and (c) to inhibit fibrosis development. However, the main important goal is to find new disease modifier treatments, which will profoundly modify the progression of the disease without major toxicity. Presently the most promising approaches consist of the inhibition of telomerase and the combination of JAK2 inhibitors (ruxolitinib) with either a BCL2/BCL-xL or BET inhibitor. Yet, the most straightforward future approaches can be considered to be the development of and/or selective inhibition of JAK2V617F and the targeting MPL and calreticulin mutants by immunotherapy. It can be expected that the therapy of MF will be significantly improved in the coming years.
PubMed: 37771602
DOI: 10.12703/r/12-23 -
Journal of Hematology & Oncology Jul 2023Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by bone marrow fibrosis, anemia, extramedullary hematopoiesis, and splenomegaly. Patients with... (Review)
Review
Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by bone marrow fibrosis, anemia, extramedullary hematopoiesis, and splenomegaly. Patients with MF are at risk for reduced survival versus the general population and often experience burdensome signs and symptoms that reduce quality of life. The oral Janus kinase (JAK) 1/JAK2 inhibitor ruxolitinib was initially approved by the US Food and Drug Administration in 2011 for the treatment of patients with intermediate or high-risk MF, including primary MF, post-polycythemia vera MF, and post-essential thrombocythemia MF, based on efficacy and safety findings from the randomized, controlled, phase 3 COMFORT trials. Over a decade later, ruxolitinib continues to be the standard of care in higher-risk MF, and dose optimization and management remain crucial for safely maximizing clinical benefits of ruxolitinib. This review summarizes the safety profile of ruxolitinib in patients with MF in the COMFORT trials leading up to approval and in the subsequent JUMP, ROBUST, EXPAND, and REALISE trials; in pooled analyses; and in postmarketing analyses in the 10 years following approval. There is a focus on the occurrence of common hematologic and nonhematologic adverse events, with guidance provided on the management of patients with anemia or thrombocytopenia, including dosing strategies based on findings from the REALISE and EXPAND trials. Finally, to ensure a greater understanding of the safety profile of ruxolitinib, practical considerations are discussed.
Topics: Humans; Primary Myelofibrosis; Quality of Life; Janus Kinase 2; Nitriles; Pyrimidines
PubMed: 37501130
DOI: 10.1186/s13045-023-01471-z -
ELife Aug 2023Erythroblasts possess unique characteristics as they undergo differentiation from hematopoietic stem cells. During terminal erythropoiesis, these cells incorporate large...
Erythroblasts possess unique characteristics as they undergo differentiation from hematopoietic stem cells. During terminal erythropoiesis, these cells incorporate large amounts of iron in order to generate hemoglobin and ultimately undergo enucleation to become mature red blood cells, ultimately delivering oxygen in the circulation. Thus, erythropoiesis is a finely tuned, multifaceted process requiring numerous properly timed physiological events to maintain efficient production of 2 million red blood cells per second in steady state. Iron is required for normal functioning in all human cells, the erythropoietic compartment consuming the majority in light of the high iron requirements for hemoglobin synthesis. Recent evidence regarding the crosstalk between erythropoiesis and iron metabolism sheds light on the regulation of iron availability by erythroblasts and the consequences of insufficient as well as excess iron on erythroid lineage proliferation and differentiation. In addition, significant progress has been made in our understanding of dysregulated iron metabolism in various congenital and acquired malignant and non-malignant diseases. Finally, we report several actual as well as theoretical opportunities for translating the recently acquired robust mechanistic understanding of iron metabolism regulation to improve management of patients with disordered erythropoiesis, such as anemia of chronic inflammation, β-thalassemia, polycythemia vera, and myelodysplastic syndromes.
Topics: Humans; Erythropoiesis; Erythrocytes; Iron; beta-Thalassemia; Hemoglobins
PubMed: 37578340
DOI: 10.7554/eLife.90189