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International Journal of Laboratory... Jun 2023Myeloproliferative neoplasms (MPN) are a group of clonal haematological malignancies first described by Dameshek in 1957. The Philadelphia-negative MPN that will be... (Review)
Review
Myeloproliferative neoplasms (MPN) are a group of clonal haematological malignancies first described by Dameshek in 1957. The Philadelphia-negative MPN that will be described are polycythaemia vera (PV), essential thrombocythaemia (ET), pre-fibrotic myelofibrosis and primary myelofibrosis (PMF). The blood and bone marrow morphology are essential in diagnosis, for WHO classification, establishing a baseline, monitoring response to treatment and identifying changes that may indicate disease progression. The blood film changes may be in any of the cellular elements. The key bone marrow features are architecture and cellularity, relative complement of individual cell types, reticulin content and bony structure. Megakaryocytes are the most abnormal cell and key to classification, as their number, location, size and cytology are all disease-defining. Reticulin content and grade are integral to assignment of the diagnosis of myelofibrosis. Even with careful assessment of all these features, not all cases fit neatly into the diagnostic entities; there is frequent overlap reflecting the biological disease continuum rather than distinct entities. Notwithstanding this, an accurate morphologic diagnosis in MPN is crucial due to the significant differences in prognosis between different subtypes and the availability of different therapies in the era of novel agents. The distinction between "reactive" and MPN is also not always straightforward and caution needs to be exercised given the prevalence of "triple negative" MPN. Here we describe the morphology of MPN including comments on changes with disease evolution and with treatment.
Topics: Humans; Primary Myelofibrosis; Reticulin; Myeloproliferative Disorders; Bone Marrow; Polycythemia Vera
PubMed: 37211431
DOI: 10.1111/ijlh.14086 -
Deutsche Medizinische Wochenschrift... Jul 2022
Topics: Humans; Polycythemia
PubMed: 35785786
DOI: 10.1055/a-1828-4185 -
American Journal of Therapeutics
Topics: Humans; Polycythemia; Phenylurea Compounds; Quinolines
PubMed: 36989234
DOI: 10.1097/MJT.0000000000001606 -
European Journal of Pharmaceutical... May 2020As a carbonic anhydrase inhibitor and a methylated lipophilic analogue of acetazolamide, Methazolamide has higher lipid solubility, less plasma protein binding and renal... (Review)
Review
As a carbonic anhydrase inhibitor and a methylated lipophilic analogue of acetazolamide, Methazolamide has higher lipid solubility, less plasma protein binding and renal excretion, and fewer side effects, compared to acetazolamide. Methazolamide can increase systemic metabolic acidosis and sequentially improve ventilation and oxygenation level. The increased oxygenation level leads to reduced reactive oxygen species (ROS) production, relived cerebral edema, mitigated hypoxic pulmonary vasoconstriction, abrogated hypoxic fatigue, and decreased excessive erythrocytosis. In addition to the effect as a carbonic anhydrase inhibitor, methazolamide directly activates the transcription factor anti-oxidative nuclear factor-related factor 2 (Nrf2) and inhibits interleukin-1β (IL-1β) release. These pharmacological functions of methazolamide are beneficial for the prevention and treatment of high-altitude illnesses. Besides, methazolamide causes less fatigue side effects than acetazolamide does. It is also worth noting that several studies suggested that a lower dose of methazolamide has similar prophylaxis and treatment efficacy in acute mountain sickness (AMS) to a higher dose of acetazolamide. Given methazolamide's advantages over acetazolamide, methazolamide may thus represent an alternative for acetazolamide when taken for high-altitude illnesses prophylaxis and treatment. However, more in-depth clinical trials are needed to fully evaluate this efficacy of methazolamide.
Topics: Acetazolamide; Altitude Sickness; Humans; Hypoxia; Methazolamide; Oxidative Stress; Oxygen; Polycythemia; Vasoconstriction
PubMed: 32251722
DOI: 10.1016/j.ejps.2020.105326 -
International Journal of Impotence... Nov 2022Secondary erythrocytosis is one of the most common adverse events associated with testosterone therapy (TT). Upon encountering this, clinicians will often either adjust... (Review)
Review
Secondary erythrocytosis is one of the most common adverse events associated with testosterone therapy (TT). Upon encountering this, clinicians will often either adjust TT dosing, stop therapy, order a phlebotomy, or recommend a combination of these. Despite this, the evidence for secondary polycythemia causing harm during TT is scarce, and the hematocrit-based cutoffs present in multiple guidelines appear to be arbritrarily chosen. In this review, we present the pathophysiology behind TT and secondary erythrocytosis, the evidence connecting TT, secondary erythrocytosis and major adverse cardiovascular events (MACE), and the data supporting varying interventions upon diagnosis of secondary erythrocytosis.
Topics: Humans; Polycythemia; Testosterone; Hematocrit; Phlebotomy
PubMed: 34987178
DOI: 10.1038/s41443-021-00509-5 -
High Altitude Medicine & Biology Mar 2022Syed, Maryam J., Ismail A. Khatri, Wasim Alamgir, and Mohammad Wasay. Stroke at moderate and high altitude. . 23:1-7, 2022. Stroke at high altitude is an understudied... (Review)
Review
Syed, Maryam J., Ismail A. Khatri, Wasim Alamgir, and Mohammad Wasay. Stroke at moderate and high altitude. . 23:1-7, 2022. Stroke at high altitude is an understudied area in stroke research. With improvements in road infrastructure, access to high-altitude areas for recreation and living purposes has risen. Subsequently, it has been anticipated that due to normal physiological changes to high altitude the incidence of stroke is also likely to increase in these regions. We searched PubMed for available literature about stroke at high altitude. Cross-referencing was done from available articles and through other scientific search engines. Relevant case series and case reports were included in this review of the topic. Only one review article, eight case series (including review of literature), and seven case reports were identified that could be included in this review. Most of the available data come from moderate and high altitude. There is limited available literature about stroke at high and extreme altitudes. Stroke at high altitude is likely to become an important subset of stroke population. Currently, there is inadequate knowledge about the incidence and prevalence, mechanisms, and stroke outcomes. Cerebral venous thrombosis is more common than arterial stroke. Stroke is probably secondary to conventional risk factors, polycythemia, and other coagulopathies. A case-control study may identify the at-risk population for stroke at moderate and high altitudes.
Topics: Altitude; Case-Control Studies; Humans; Polycythemia; Risk Factors; Stroke
PubMed: 34637624
DOI: 10.1089/ham.2021.0043 -
Blood Apr 2020The TEMPI syndrome is a rare and acquired disorder characterized by 5 salient features, which compose its name: (1) telangiectasias; (2) elevated erythropoietin and...
The TEMPI syndrome is a rare and acquired disorder characterized by 5 salient features, which compose its name: (1) telangiectasias; (2) elevated erythropoietin and erythrocytosis; (3) monoclonal gammopathy; (4) perinephric fluid collections; and (5) intrapulmonary shunting. Complete resolution of symptoms following treatment with plasma cell-directed therapy supports the hypothesis that the monoclonal antibody is causal and pathogenic. Understanding the basis of the TEMPI syndrome will depend on the identification of additional patients and a coordinated international effort.
Topics: Erythropoietin; Humans; Lung Diseases; Paraproteinemias; Polycythemia; Syndrome; Telangiectasis
PubMed: 32108223
DOI: 10.1182/blood.2019004216 -
The New England Journal of Medicine Feb 2024Polycythemia vera is a chronic myeloproliferative neoplasm characterized by erythrocytosis. Rusfertide, an injectable peptide mimetic of the master iron regulatory... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Polycythemia vera is a chronic myeloproliferative neoplasm characterized by erythrocytosis. Rusfertide, an injectable peptide mimetic of the master iron regulatory hormone hepcidin, restricts the availability of iron for erythropoiesis. The safety and efficacy of rusfertide in patients with phlebotomy-dependent polycythemia vera are unknown.
METHODS
In part 1 of the international, phase 2 REVIVE trial, we enrolled patients in a 28-week dose-finding assessment of rusfertide. Part 2 was a double-blind, randomized withdrawal period in which we assigned patients, in a 1:1 ratio, to receive rusfertide or placebo for 12 weeks. The primary efficacy end point was a response, defined by hematocrit control, absence of phlebotomy, and completion of the trial regimen during part 2. Patient-reported outcomes were assessed by means of the modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) patient diary (scores range from 0 to 10, with higher scores indicating greater severity of symptoms).
RESULTS
Seventy patients were enrolled in part 1 of the trial, and 59 were assigned to receive rusfertide (30 patients) or placebo (29 patients) in part 2. The estimated mean (±SD) number of phlebotomies per year was 8.7±2.9 during the 28 weeks before the first dose of rusfertide and 0.6±1.0 during part 1 (estimated difference, 8.1 phlebotomies per year). The mean maximum hematocrit was 44.5±2.2% during part 1 as compared with 50.0±5.8% during the 28 weeks before the first dose of rusfertide. During part 2, a response was observed in 60% of the patients who received rusfertide as compared with 17% of those who received placebo (P = 0.002). Between baseline and the end of part 1, rusfertide treatment was associated with a decrease in individual symptom scores on the MPN-SAF in patients with moderate or severe symptoms at baseline. During parts 1 and 2, grade 3 adverse events occurred in 13% of the patients, and none of the patients had a grade 4 or 5 event. Injection-site reactions of grade 1 or 2 in severity were common.
CONCLUSIONS
In patients with polycythemia vera, rusfertide treatment was associated with a mean hematocrit of less than 45% during the 28-week dose-finding period, and the percentage of patients with a response during the 12-week randomized withdrawal period was greater with rusfertide than with placebo. (Funded by Protagonist Therapeutics; REVIVE ClinicalTrials.gov number, NCT04057040.).
Topics: Humans; Hematocrit; Hepcidins; Iron; Polycythemia; Polycythemia Vera; Peptides; Injections; Double-Blind Method; Hematologic Agents
PubMed: 38381675
DOI: 10.1056/NEJMoa2308809 -
Sexual Medicine Reviews Jan 2021Testosterone prescriptions have increased dramatically in recent years, largely because of changes in expert guidelines. Concerns have been raised that testosterone... (Review)
Review
INTRODUCTION
Testosterone prescriptions have increased dramatically in recent years, largely because of changes in expert guidelines. Concerns have been raised that testosterone therapy (TTh) may be associated with an increased incidence of conditions such as cardiovascular (CV) disease, thromboembolic events, obstructive sleep apnea (OSA), benign prostatic hyperplasia (BPH), and prostate cancer (PCa) and also may be a beneficial therapy in the management of prediabetes. As such, considerable debate remains regarding which hypogonadal populations are appropriate candidates for TTh.
OBJECTIVES
This systematic review aims to affirm or refute, using the most current evidence, the published concerns surrounding TTh and its potential increased risk of conditions such as CV disease, thromboembolic events, OSA, urolithiasis, BPH, and PCa, as well as its role as a potential tool for managing prediabetes.
METHODS
A systematic review of literature surrounding TTh and its impact on increasing risk for the adverse conditions mentioned previously was performed. 62 publications were selected for inclusion based on their relevance to the effects and risks of TTh. Evidence is current through December 2019.
RESULTS
Evidence demonstrates that positive associations exist between TTh and OSA, erythrocytosis, as well as urolithiasis. TTh may potentially be used to treat hypogonadal men with prediabetes. While low testosterone is positively correlated with adverse CV events, TTh in hypogonadal men either has no effect or decreases such risk. TTh is likely not associated with increased risk of PCa incidence or recurrence.
CONCLUSIONS
Despite historical beliefs that TTh increases the risk of CV disease, thromboembolic events, BPH, and PCa, recent evidence suggests that TTh conveys less risk than previously perceived. While caution should continue to be exercised, evidence suggests that TTh is a reasonable treatment option in many hypogonadal men who were previously excluded from TTh based on risk factors and prior health histories. Twitchell DK, Pastuszak AW, Khera M. Controversies in Testosterone Therapy. Sex Med Rev 2021;9:149-159.
Topics: Hormone Replacement Therapy; Humans; Hypogonadism; Male; Polycythemia; Prostatic Neoplasms; Testosterone
PubMed: 33309270
DOI: 10.1016/j.sxmr.2020.09.004 -
Genes Jul 2021True erythrocytosis is present when the red cell mass is greater than 125% of predicted sex and body mass, which is reflected by elevated hemoglobin and hematocrit.... (Review)
Review
True erythrocytosis is present when the red cell mass is greater than 125% of predicted sex and body mass, which is reflected by elevated hemoglobin and hematocrit. Erythrocytosis can be primary or secondary and congenital or acquired. Congenital defects are often found in those diagnosed at a young age and with a family history of erythrocytosis. Primary congenital defects mainly include mutations in the gene but has also been implicated. Secondary congenital erythrocytosis can arise through a variety of genetic mechanisms, including mutations in the genes in the oxygen sensing pathway, with high oxygen affinity hemoglobin variants and mutations in other genes such as , where ultimately the production of erythropoietin is increased, resulting in erythrocytosis. Recently, mutations in have been associated with erythrocytosis. In many cases, a genetic variant cannot be identified, leaving a group of patients with the label idiopathic erythrocytosis who should be the subject of future investigations. The clinical course in congenital erythrocytosis is hard to evaluate as these are rare cases. However, some of these patients may well present at a young age and with sometimes catastrophic thromboembolic events. There is little evidence to guide the management of congenital erythrocytosis but the use of venesection and low dose aspirin should be considered.
Topics: Humans; Infant, Newborn; Infant, Newborn, Diseases; Mutation; Polycythemia
PubMed: 34440325
DOI: 10.3390/genes12081151