-
CEN Case Reports Apr 2024A 66-year-old non-smoker presented with a 2-week history of new-onset pedal oedema and gross haematuria. On evaluation, he was found to be hypertensive and oedematous...
A 66-year-old non-smoker presented with a 2-week history of new-onset pedal oedema and gross haematuria. On evaluation, he was found to be hypertensive and oedematous with a haemoglobin of 19.1 g/dl, platelet count of 546,000/mm, and creatinine of 2.6 mg/dl. Urine examination revealed abundant RBCs with 3+ albumin on three separate occasions. His 24-h urine protein level was 3830 mg/day, with a serum cholesterol level of 303 mg/dl. Secondary erythrocytosis and thrombocytosis tests were negative. Bone marrow examination revealed hypercellularity, erythroid hyperplasia, tight clusters of large megakaryocytes, and megakaryocytic hyperplasia suggestive of polycythemia vera. PCR analysis revealed a JAK2V617 F (exon 14) mutation. In view of nephrotic syndrome, azotemia, and microscopic haematuria, a renal biopsy was performed, which revealed features of IgA nephropathy with advanced interstitial fibrosis and tubular atrophy. He was started on angiotensin receptor blockers with hydroxy urea as a part of treatment. This case report highlights the association of glomerular disease with polycythaemia vera and the need of prompt renal biopsy for diagnosis and management.
PubMed: 38643434
DOI: 10.1007/s13730-024-00879-x -
ELife Apr 2024High-altitude polycythemia (HAPC) affects individuals living at high altitudes, characterized by increased red blood cells (RBCs) production in response to hypoxic...
High-altitude polycythemia (HAPC) affects individuals living at high altitudes, characterized by increased red blood cells (RBCs) production in response to hypoxic conditions. The exact mechanisms behind HAPC are not fully understood. We utilized a mouse model exposed to hypobaric hypoxia (HH), replicating the environmental conditions experienced at 6000 m above sea level, coupled with in vitro analysis of primary splenic macrophages under 1% O to investigate these mechanisms. Our findings indicate that HH significantly boosts erythropoiesis, leading to erythrocytosis and splenic changes, including initial contraction to splenomegaly over 14 days. A notable decrease in red pulp macrophages (RPMs) in the spleen, essential for RBCs processing, was observed, correlating with increased iron release and signs of ferroptosis. Prolonged exposure to hypoxia further exacerbated these effects, mirrored in human peripheral blood mononuclear cells. Single-cell sequencing showed a marked reduction in macrophage populations, affecting the spleen's ability to clear RBCs and contributing to splenomegaly. Our findings suggest splenic ferroptosis contributes to decreased RPMs, affecting erythrophagocytosis and potentially fostering continuous RBCs production in HAPC. These insights could guide the development of targeted therapies for HAPC, emphasizing the importance of splenic macrophages in disease pathology.
Topics: Animals; Mice; Humans; Spleen; Altitude Sickness; Splenomegaly; Ferroptosis; Leukocytes, Mononuclear; Macrophages; Hypoxia
PubMed: 38629942
DOI: 10.7554/eLife.87496 -
American Journal of Veterinary Research Jun 2024The aim of this study was to assess the efficacy and safety of a third-generation lentivirus-based vector encoding the feline erythropoietin (EPO) (feEPO) gene in vitro...
A lentivirus-vectored feline erythropoietin gene therapy strategy in tissue culture and rodent models for the potential treatment of chronic renal disease-associated anemia.
OBJECTIVE
The aim of this study was to assess the efficacy and safety of a third-generation lentivirus-based vector encoding the feline erythropoietin (EPO) (feEPO) gene in vitro and in rodent models in vivo. This vector incorporates a genetic mechanism to facilitate the termination of the therapeutic effect in the event of supraphysiologic polycythemia, the herpes simplex virus thymidine kinase (HSV-TK) "suicide gene."
ANIMALS
CFRK cells and replication-defective lentiviral vectors encoding feEPO were used for in vitro experiments. Eight Fischer rats were enrolled in the pilot in vivo study, 24 EPO-deficient mice were used in the initial mouse study, and 15 EPO-deficient mice were enrolled in the final mouse study.
METHODS
Efficacy of a third-generation lentivirus encoding feEPO was determined in vitro using western blot assays. Subsequently, in a series of rodent experiments, animals were administered the viral vector in progressively increasing inoculation doses with serial measurements of blood packed cell volume (PCV) over time.
RESULTS
We documented production of feEPO protein in transduced CRFK cells with subsequent cessation of production when treated with the HSV-TK substrate ganciclovir. In vivo, we demonstrated variably persistent elevated PCV values in treated rats and mice with eventual return to baseline values over time.
CLINICAL RELEVANCE
These results provide justification for a lentiviral gene therapy approach to the treatment of nonregenerative anemia associated with chronic renal disease in cats.
Topics: Animals; Erythropoietin; Genetic Therapy; Lentivirus; Mice; Anemia; Cats; Genetic Vectors; Rats; Rats, Inbred F344; Renal Insufficiency, Chronic; Male; Female; Cell Line
PubMed: 38626794
DOI: 10.2460/ajvr.23.12.0280 -
International Journal of Molecular... Apr 2024The Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-MPNs) are a heterogeneous group of clonal hematopoietic malignancies that include polycythemia vera...
Conventional Cytogenetic Analysis and Array CGH + SNP Identify Essential Thrombocythemia and Prefibrotic Primary Myelofibrosis Patients Who Are at Risk for Disease Progression.
The Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-MPNs) are a heterogeneous group of clonal hematopoietic malignancies that include polycythemia vera (PV), essential thrombocythemia (ET), and the prefibrotic form of primary myelofibrosis (prePMF). In this study, we retrospectively reviewed the karyotypes from conventional cytogenetics (CC) and array Comparative Genomic Hybridization + Single Nucleotide Polymorphism (aCGH + SNP) in patients with ET or prePMF to determine whether the combined analysis of both methodologies can identify patients who may be at a higher risk of disease progression. We performed a comprehensive genomic review on 169 patients with a clinical diagnosis of ET (154 patients) or prePMF (15 patients). Genomic alterations detected by CC or array-CGH + SNP were detected in 36% of patients. In patients who progressed, 68% had an abnormal genomic finding by either technology. There was a shorter progression-free survival (PFS) among patients who were cytogenetically abnormal or who were cytogenetically normal but had an abnormal aCGH + SNP result. Leveraging the ability to detect submicroscopic copy number alterations and regions of copy neutral-loss of heterozygosity, we identified a higher number of patients harboring genomic abnormalities than previously reported. These results underscore the importance of genomic analysis in prognostication and provide valuable information for clinical management and treatment decisions.
Topics: Humans; Comparative Genomic Hybridization; Thrombocythemia, Essential; Polymorphism, Single Nucleotide; Primary Myelofibrosis; Retrospective Studies; Cytogenetic Analysis; Disease Progression
PubMed: 38612873
DOI: 10.3390/ijms25074061 -
Cancers Apr 2024Myelofibrosis (MF) is a myeloproliferative neoplasia arising de novo as primary myelofibrosis (PMF) or secondary to polycythemia vera or essential thrombocythemia....
Myelofibrosis (MF) is a myeloproliferative neoplasia arising de novo as primary myelofibrosis (PMF) or secondary to polycythemia vera or essential thrombocythemia. Patients experience a high symptom burden and a marked reduction in life expectancy. Despite progress in molecular understanding and treatment, the clinical and prognostic heterogeneity of MF complicates treatment decisions. The International Prognostic Scoring System (IPSS) integrates clinical factors for risk stratification in MF. This study leverages the TriNetX database with more than 64,000 MF patients to assess the impact of accessible parameters on survival and complicating events, including AML transformation, cachexia, increased systemic inflammation, thrombosis and hemorrhage. Age over 65 years correlated with increased risks of death, AML transformation, thrombosis and hemorrhage. Anemia (Hb < 10 g/dL), leukocytosis (>25 × 10/µL) and thrombocytopenia (<150 × 10/µL) reduced survival and increased risks across all assessed events. Monocytosis is associated with decreased survival, whereas eosinophilia and basophilia were linked to improved survival. Further, as proof of concept for the applicability of TriNetX for clinical scores, we devised a simplified IPSS, and confirmed its value in predicting outcomes. This comprehensive study underscores the importance of age, anemia, leukocytosis and thrombocytopenia in predicting disease trajectory and contributes to refining prognostic models, addressing the challenges posed by the disease's heterogeneity.
PubMed: 38611094
DOI: 10.3390/cancers16071416 -
Cureus Mar 2024Myeloproliferative neoplasms (MPNs) present a unique challenge in surgical management due to their inherent predisposition to both bleeding and thrombosis. MPNs are a... (Review)
Review
Myeloproliferative neoplasms (MPNs) present a unique challenge in surgical management due to their inherent predisposition to both bleeding and thrombosis. MPNs are a heterogenous group of acquired clonal conditions. The three classic MPNs are essential thrombocythemia (ET), myelofibrosis (PMF), and polycythemia vera (PV). All subtypes of MPN are associated with both thrombotic and bleeding complications. There are four risk categories for thrombosis in MPN patients: age, thrombosis history, and -2 mutation. They are further classified as very low, low, intermediate, and high risk. The genetic landscape of MPN is fascinating and complex like all myeloid disorders. Bleeding risk can be assessed through leukocytosis, thrombocytosis, acquired von Willebrand syndrome (AVWS), and a previous history of bleeding in a patient. Risk assessment and perioperative management are important aspects of improving the quality of life and preventing complications in surgeries. Preoperative management includes a risk assessment of venous thromboembolism, use of appropriate pharmacological treatment, platelet count control, and correction and cardiovascular risk factors. This review summarizes the assessment of bleeding and thrombosis risk for patients with MPNs scheduled for surgery. Furthermore, this review discusses various tools that can be used to identify MPN patients at risk of thrombosis prior to surgery.
PubMed: 38606222
DOI: 10.7759/cureus.56008 -
Journal of Clinical Medicine Feb 2024: Malnutrition is an underdiagnosed condition that negatively affects the clinical outcomes of patients, being associated with an increased risk of adverse events,...
: Malnutrition is an underdiagnosed condition that negatively affects the clinical outcomes of patients, being associated with an increased risk of adverse events, increased hospital stay, and higher mortality. Therefore, nutritional assessment is a required and necessary process in patient care. The objective of this study was to identify the factors associated with nutritional risk by applying the Malnutrition Universal Screening Tool (MUST) scale in a population of critically ill patients. : This was an observational, analytical, and retrospective study. Sociodemographic, clinical, hematological, and biochemical variables and their relationship with nutritional risk and mortality were analyzed. : Of 630 patients, the leading cause of admission was pathologies of the circulatory and respiratory system (50%); 28.4% were at high nutritional risk; and mortality was 11.6% and associated with nutritional risk, hemoglobin, and plasma urea nitrogen. : The presence of gastrointestinal symptoms and the type of nutritional support received during hospitalization could increase the likelihood of presenting a medium/high nutritional risk, while polycythemia reduced this probability. An associative model was found to determine nutritional risk with an adequate specificity and diagnostic validity index.
PubMed: 38592073
DOI: 10.3390/jcm13051236 -
Medicine Apr 2024Primary myelofibrosis is a subtype of myeloproliferative neoplasm that leads to bone marrow fibrosis. Historically, the only curative option for primary myelofibrosis... (Review)
Review
RATIONALE
Primary myelofibrosis is a subtype of myeloproliferative neoplasm that leads to bone marrow fibrosis. Historically, the only curative option for primary myelofibrosis was allogeneic hematopoietic stem cell transplant. Ruxolitinib, a Janus kinase inhibitor, is now used for the treatment of primary myelofibrosis and polycythemia vera. It effectively improves symptoms related to splenomegaly and anemia. However, its association with the development of opportunistic infections has been observed in clinical studies and practical application.
PATIENT CONCERNS
A 64-year-old female with primary myelofibrosis and chronic hepatitis B infection who received ruxolitinib treatment. She was admitted for spiking fever and altered consciousness.
DIAGNOSIS
Tuberculosis meningitis was suspected but cerebrospinal fluid can't identify any pathogens. An abdominal computed tomography scan revealed a left psoas abscess and an enlarged spleen. A computed tomography-guided pus drainage procedure was performed, showing a strong positive acid-fast stain and a positive Mycobacterium tuberculosis polymerase chain reaction result.
INTERVENTIONS
antituberculosis medications were administered. The patient developed a psoas muscle abscess caused by tuberculosis and multiple dermatomes of herpes zoster during antituberculosis treatment.
OUTCOMES
The patient was ultimately discharged after 6 weeks of treatment without apparent neurological sequelae.
LESSONS
This case underscores the importance of clinicians evaluating latent infections and ensuring full vaccination prior to initiating ruxolitinib-related treatment for primary myelofibrosis.
Topics: Female; Humans; Middle Aged; Nitriles; Primary Myelofibrosis; Psoas Abscess; Psoas Muscles; Pyrazoles; Pyrimidines; Splenomegaly; Tuberculosis
PubMed: 38579059
DOI: 10.1097/MD.0000000000037653 -
Medicine Apr 2024The demand for Janus Kinase-2 (JAK2) testing has been disproportionate to the low yield of positive results, which highlights the need for more discerning test...
The demand for Janus Kinase-2 (JAK2) testing has been disproportionate to the low yield of positive results, which highlights the need for more discerning test strategies. The aim of this study is to introduce an artificial intelligence application as a more rational approach for testing JAK2 mutations in cases of erythrocytosis. Test results were sourced from samples sent to a tertiary hospital's genetic laboratory between 2017 and 2023, meeting 2016 World Health Organization criteria for JAK2V617F mutation testing. The JAK2 Somatic Mutation Screening Kit was used for genetic testing. Machine learning models were trained and tested using Python programming language. Out of 458 cases, JAK2V617F mutation was identified in 13.3%. There were significant differences in complete blood count parameters between mutation carriers and non-carriers. Various models were trained with data, with the random forest (RF) model demonstrating superior precision, recall, F1-score, accuracy, and area under the receiver operating characteristic, all reaching 100%. Gradient boosting (GB) model also showed high scores. When compared with existing algorithms, the RF and GB models displayed superior performance. The RF and GB models outperformed other methods in accurately identifying and classifying erythrocytosis cases, offering potential reductions in unnecessary testing and costs.
Topics: Humans; Artificial Intelligence; Polycythemia; Machine Learning; Algorithms; Hemoglobins; Janus Kinase 2
PubMed: 38579024
DOI: 10.1097/MD.0000000000037751 -
Chronic Obstructive Pulmonary Diseases... May 2024The prevalence of iron deficiency in patients with chronic obstructive pulmonary disease (COPD) varies in previous studies. We aimed to assess its prevalence according...
BACKGROUND
The prevalence of iron deficiency in patients with chronic obstructive pulmonary disease (COPD) varies in previous studies. We aimed to assess its prevalence according to 3 well-known criteria for iron deficiency, its associations with clinical characteristics of COPD, and mortality.
METHODS
In a cohort study consisting of 84 COPD patients, of which 21 had chronic respiratory failure, and 59 were non-COPD controls, ferritin, transferrin saturation (TSat), and mortality across 6.5 years were assessed. Associations between clinical characteristics and iron deficiency were examined by logistic regression, while associations with mortality were assessed in mixed effects Cox regression analyses.
RESULTS
The prevalence of iron deficiency in the study population was 10%-43% according to diagnostic criteria, and was consistently higher in individuals with COPD, peaking at 71% in participants with chronic respiratory failure. Ferritin < cutoff was significantly associated with forced expiratory volume in 1 second (FEV) (odds ratio [OR] 0.33 per liter increase), smoking (OR 3.2), and cardiovascular disease (OR 4.7). TSat < 20% was associated with body mass index (BMI) (OR 1.1 per kg/m increase) and hemoglobin (OR 0.65 per g/dL increase). The combined criterion of low ferritin and TSat was only associated with FEV (OR 0.39 per liter increase). Mortality was not significantly associated with iron deficiency (hazard ratio [HR] 1.2-1.8).
CONCLUSION
The prevalence of iron deficiency in the study population increased with increasing severity of COPD. Iron deficiency, defined by ferritin < cutoff, was associated with bronchial obstruction, current smoking, and cardiovascular disease, while TSat < 20% was associated with reduced levels of hemoglobin and increased BMI. Iron deficiency was not associated with increased mortality.
PubMed: 38575374
DOI: 10.15326/jcopdf.2023.0477