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BMC Cardiovascular Disorders Oct 2023The role of hemoglobin (Hb) level in the short-term prognosis of patients with acute decompensated heart failure (ADHF) remains a matter of debate. We aimed to declare...
BACKGROUND
The role of hemoglobin (Hb) level in the short-term prognosis of patients with acute decompensated heart failure (ADHF) remains a matter of debate. We aimed to declare the prevalence of, association with, severity of, and prognostic role of SHL with ADHF.
METHODS
Using the data from the Persian Registry Of Cardiovascular Disease/ Heart Failure (PROVE-HF) study, we assessed the association between anemia and polycythemia (Hb < 13 g/dLit, > 16.5 g/dLit in males and < 12 g/dLit, and > 16 g/dLit in females, respectively) and short-term mortality using Cox proportional hazard modeling, with adjustment of clinically relevant variables.
RESULTS
Of 3652 ADHF patients, anemia was seen in 1673 patients (48.40%). The prevalence of mild, moderate, and severe anemia was 42.33% (n = 1546), 3.23% (n = 118), and 0.24% (n = 9), respectively. Also, 422 patients (11.55%) had polycythemia. Compared to non-anemic patients, anemic patients were mainly male, older, and were more likely to have diabetes mellitus (DM), renal dysfunction, hypertension (HTN), and thyroid disease. Significant predictors of short-term mortality were lower systolic and diastolic blood pressure, lower Hb level, and higher blood urea nitrogen (BUN). Anemic patients had higher all-cause mortality [adjusted hazard ratio (aHR) 1.213, 95% confidence interval [CI] 1.054-1.396]. Moderate anemia increased mortality by approximately 80% in males (aHR 1.793, 95% CI 1.308-2.458) and females (aHR 1.790, 95% CI 1.312-2.442), respectively. Polycythemia had no association with short-term mortality in both genders (P-value > 0.05).
CONCLUSIONS
This study revealed that anemia is an adverse prognostic factor for short-term mortality in ADHF patients, with higher mortality in moderately anemic patients.
Topics: Humans; Male; Female; Prognosis; Prevalence; Polycythemia; Heart Failure; Anemia; Hemoglobins
PubMed: 37794317
DOI: 10.1186/s12872-023-03510-6 -
Stem Cell Reports Feb 2024The myeloproliferative disease polycythemia vera (PV) driven by the JAK2 V617F mutation can transform into myelofibrosis (post-PV-MF). It remains an open question how...
The myeloproliferative disease polycythemia vera (PV) driven by the JAK2 V617F mutation can transform into myelofibrosis (post-PV-MF). It remains an open question how JAK2 V617F in hematopoietic stem cells induces MF. Megakaryocytes are major players in murine PV models but are difficult to study in the human setting. We generated induced pluripotent stem cells (iPSCs) from JAK2 V617F PV patients and differentiated them into megakaryocytes. In differentiation assays, JAK2 V617F iPSCs recapitulated the pathognomonic skewed megakaryocytic and erythroid differentiation. JAK2 V617F iPSCs had a TPO-independent and increased propensity to differentiate into megakaryocytes. RNA sequencing of JAK2 V617F iPSC-derived megakaryocytes reflected a proinflammatory, profibrotic phenotype and decreased ribosome biogenesis. In three-dimensional (3D) coculture, JAK2 V617F megakaryocytes induced a profibrotic phenotype through direct cell contact, which was reversed by the JAK2 inhibitor ruxolitinib. The 3D coculture system opens the perspective for further disease modeling and drug discovery.
Topics: Humans; Mice; Animals; Bone Marrow; Megakaryocytes; Induced Pluripotent Stem Cells; Janus Kinase 2; Polycythemia Vera; Phenotype; Fibrosis; Mutation
PubMed: 38278152
DOI: 10.1016/j.stemcr.2023.12.011 -
Colombia Medica (Cali, Colombia) 2023Among the chronic myeloproliferative neoplasms (MPNs) not associated with BCR-ABL mutations are polycythemia vera, primary myelofibrosis, and essential thrombocythemia....
BACKGROUND
Among the chronic myeloproliferative neoplasms (MPNs) not associated with BCR-ABL mutations are polycythemia vera, primary myelofibrosis, and essential thrombocythemia. These diseases are caused by mutations in genes, such as the JAK2, MPL, and CALR genes, which participate in regulating the JAK-STAT signaling pathway.
OBJECTIVE
This study aimed to establish the frequencies of mutations in the JAK2, MPL, and CALR genes in a group of Colombian patients with a negative clinical diagnosis of BCR-ABL chronic myeloproliferative neoplasms.
METHODS
The JAK2 V617F and MPL W515K mutations and deletions or insertions in exon 9 of the CALR gene were analyzed in 52 Colombian patients with polycythemia vera, primary myelofibrosis, and essential thrombocythemia.
RESULTS
The JAK2V617F mutation was carried by 51.9% of the patients, the CALR mutation by 23%, and the MPL mutation by 3.8%; 23% were triple-negative for the mutations analyzed. In these neoplasms, 6 mutation types in CALR were identified, one of which has not been previously reported. Additionally, one patient presented a double mutation in both the CALR and JAK2 genes. Regarding the hematological results for the mutations, significant differences were found in the hemoglobin level, hematocrit level, and platelet count among the three neoplasms.
CONCLUSION
Thus, this study demonstrates the importance of the molecular characterization of the JAK2, CALR and MPL mutations in Colombian patients (the genetic context of which remains unclear in the abovementioned neoplasms) to achieve an accurate diagnosis, a good prognosis, adequate management, and patient survival.
Topics: Humans; Colombia; Janus Kinase 2; Mutation; Myeloproliferative Disorders; Polycythemia Vera; Primary Myelofibrosis; Receptors, Thrombopoietin; Thrombocythemia, Essential; Calreticulin
PubMed: 38111518
DOI: 10.25100/cm.v54i3.5353 -
Laeknabladid Dec 2023We report a case of a 79-year-old woman with a previous history of polycythemia vera, glaucoma and hypertension. Her previous surgeries included a cholecystectomy with...
We report a case of a 79-year-old woman with a previous history of polycythemia vera, glaucoma and hypertension. Her previous surgeries included a cholecystectomy with an incidental finding of a gallbladder carcinoma with following partial liver resection and a hysterectomy. The surgery department was consulted regarding this patient due to abdominal pain in her lower abdomen and tumor in her right groin. A CT scan of the abdomen was obtained that showed a hernia with the appendix vermiformis in the hernia sac. She was operated with a preperitoneal open approach and an inflamed appendix from a femoral hernia sac was removed and a herniorrhaphy with a mesh was performed. The patient was discharged the day after the surgery. Femoral hernia with the appendix in the hernia sac is a rare type of hernia first descriped by Rene-Jacques De Garengeot in 1731 and now bearing his name.
Topics: Female; Humans; Aged; Appendectomy; Hernia, Femoral; Appendix; Herniorrhaphy; Tomography, X-Ray Computed
PubMed: 38031981
DOI: 10.17992/lbl.2023.12.772 -
ST-Segment Elevation Myocardial Infarction and Bleeding Complications in JAK2-Negative Polycythemia.Texas Heart Institute Journal Oct 2023Thrombotic and bleeding complications are major causes of morbidity and mortality in patients with polycythemia vera, who predominantly present with an alteration in the...
Thrombotic and bleeding complications are major causes of morbidity and mortality in patients with polycythemia vera, who predominantly present with an alteration in the JAK2 gene. Because of their hypercoagulable state and risk of hemorrhage, patients with polycythemia vera who present with an acute myocardial infarction pose a challenge to physicians. This case report describes the presentation and treatment of a Hispanic patient with JAK2 V617F-negative primary polycythemia who developed cardiac arrest and ST-segment elevation myocardial infarction owing to complete occlusion of the left anterior descending artery as well as bleeding complications and postmyocardial pericarditis.
Topics: Humans; Polycythemia; Polycythemia Vera; ST Elevation Myocardial Infarction; Myocardial Infarction; Thrombosis; Janus Kinase 2
PubMed: 37872693
DOI: 10.14503/THIJ-23-8148 -
Heliyon Mar 2024The primary aim of this study was to closely monitor and identify adverse events (AEs) linked to lenvatinib, a pharmacotherapeutic agent employed for the management of...
PURPOSE
The primary aim of this study was to closely monitor and identify adverse events (AEs) linked to lenvatinib, a pharmacotherapeutic agent employed for the management of renal cell carcinoma, thyroid cancer, and hepatocellular carcinoma. The ultimate goal was to optimize patient safety and provide evidence-based guidance for the appropriate utilization of this medication.
METHODS
A comprehensive collection and analysis of reports from the FDA Adverse Event Reporting System (FAERS) database was conducted, encompassing the period from the first quarter of 2015 to the first quarter of 2023. Disproportionality analysis, employing robust algorithms including ROR, PRR, BCPNN, and EBGM was employed for effective data mining to quantify signals associated with lenvatinib-related AEs.
RESULTS
Among the collected reports, a total of 15,193 cases were identified where lenvatinib was the "primary suspected (PS)" drug, resulting in 50,508 lenvatinib-induced AEs. An analysis was conducted to examine the occurrence of lenvatinib-induced adverse drug reactions (ADRs) across 26 organ systems. The findings revealed the presence of expected ADRs, including diarrhea, vomiting, stomatitis, hepatic encephalopathy, decreased appetite, dehydration, decreased weight, and electrolyte imbalances, which were consistent with the information provided in the drug labels. Furthermore, unexpected significant ADRs were observed at the preferred terms (PT) level, such as interstitial lung disease, pneumothorax, hypophysitis, failure to thrive, polycythemia, hypopituitarism, spontaneous pneumothorax, pulmonary cavitation, and limbic encephalitis. These findings indicated the potential occurrence of adverse effects that are currently not documented in the drug instructions.
CONCLUSIONS
This study has successfully detected novel and unforeseen signals pertaining to ADRs associated with the administration of lenvatinib, thereby contributing significant insights into the intricate correlation between ADRs and the utilization of lenvatinib. The outcomes of this investigation underscore the utmost significance of continuous monitoring and vigilant surveillance in order to promptly identify and effectively manage AEs, consequently enhancing overall patient safety and well-being in the context of lenvatinib therapy.
PubMed: 38524578
DOI: 10.1016/j.heliyon.2024.e28132 -
The Pan African Medical Journal 2023neonatal jaundice appears in most neonates as "physiological jaundice" in the first few weeks of life; however, pathological jaundice is associated with an increased...
Determinants of neonatal jaundice among neonates admitted to neonatal intensive care unit in public hospitals of Sidama Region, Sidama, Ethiopia, 2022: an unmatched case-control study.
INTRODUCTION
neonatal jaundice appears in most neonates as "physiological jaundice" in the first few weeks of life; however, pathological jaundice is associated with an increased risk of long-term complications and mortality only a few studies have been conducted on the determinants of neonatal jaundice in Ethiopia. The aim of this study was to identify the determinants of neonatal jaundice (pathological) among neonates admitted to neonatal intensive care units in Sidama Region general and referral public hospitals.
METHODS
a hospital-based unmatched case-control study was conducted among 270 neonates in public hospitals of Sidama Region from June 23 to August 8, 2022. We used a pre-tested interviewer-administered questionnaire and collected by open data kit (ODK) then the data was downloaded and exported to Microsoft Excel worksheets (XLS) and imported to SPSS version 26 for further analysis. Bi-variable logistic regression analysis was performed. Variables with a P-Value of less than 0.25 were included in multivariable logistic regression. Multi-variable logistic regression was performed and Adjusted Odds ratio (AOR) with a 95% confidence interval was computed and statistical significance was declared at a p-value <0.05.
RESULTS
a total of 270 neonates with mothers (90 cases and 180 controls) with a response rate of 100% were included in this study. Factors significantly increased the odds of developing neonatal jaundice were multiparty (AOR=2.869(95%CI 1.426-5.769)), prolonged duration of labor (AOR=4.618(95%CI 1.689 - 12.625)). ABO incompatibility (AOR=3.362(95%CI, 1.185 - 9.537)). Preterm (AOR=2.936(95%CI, 1.2456.923)), birthasphyxia (AOR=2.278(95%CI,1.1454.531)) and polycythemia (AOR=3.397(95%CI, 1.147-10.061)).
CONCLUSION
in this study multiparty, prolonged duration labor, ABO incompatibility, preterm gestational age, birth asphyxia, and polycythemia were factors that significantly increased the odds of developing neonatal jaundice.
Topics: Infant, Newborn; Female; Humans; Case-Control Studies; Intensive Care Units, Neonatal; Ethiopia; Jaundice, Neonatal; Polycythemia; Hospitals, Public; Jaundice
PubMed: 37745917
DOI: 10.11604/pamj.2023.45.117.40472 -
Journal of Clinical Medicine Jun 2024Polycythemia vera (PV) is a chronic hematologic neoplasm commonly treated with hydroxyurea (HU). We utilized the advanced digitalized database of Maccabi Healthcare...
Polycythemia vera (PV) is a chronic hematologic neoplasm commonly treated with hydroxyurea (HU). We utilized the advanced digitalized database of Maccabi Healthcare Services to retrospectively investigate the clinical and economic implications of HU intolerance in the routine clinical care of PV patients in Israel. We collected data on demographics, physician visits, hospitalizations, laboratory results, medication purchases, cardiovascular and thrombotic events, mental health, economic outcomes, and mortality. Outcomes included cardiovascular and other thrombotic events, disease progression, mental health events, economic outcomes, and overall mortality. Of the 830 patients studied, 3 (0.4%) were resistant to HU treatment, 318 (38.3%) were intolerant to HU treatment, and 509 (61.3%) were stable on HU treatment. The venous thrombosis rate was significantly higher among HU-intolerant compared to HU-stable patients (1.58 vs. 0.47 per 100 person-years [PY], respectively; < 0.001). The rate of progression to myelofibrosis was 6 vs. 0.9 per 100 PY in HU-intolerant patients vs. HU-stable patients, respectively ( < 0.001), and the rate of progression to acute myeloid leukemia (AML) was 1.16 vs. 0.2 per 100 PY in HU-intolerant patients vs. HU-stable patients, respectively ( < 0.001). The phlebotomy requirement, mortality rate, and total hospitalization days among HU-intolerant patients were significantly higher than in HU-stable patients ( = 0.049, < 0.001, < 0.001, respectively). More mental health-related events were noted in HU-intolerant patients vs. HU-stable patients ( = 0.007), and the total healthcare cost ratio was 2.65 for the HU-intolerant patients compared with HU-stable patients. This study suggests that HU-intolerant patients are more likely to have worse outcomes than HU-stable patients, highlighting the need for the close monitoring of these patients for disease-related complications or progression.
PubMed: 38929918
DOI: 10.3390/jcm13123390 -
Microbiology Spectrum Sep 2023Essential thrombocythemia (ET) is part of the Philadelphia chromosome-negative myeloproliferative neoplasms. It is characterized by an increased risk of thromboembolic...
Essential thrombocythemia (ET) is part of the Philadelphia chromosome-negative myeloproliferative neoplasms. It is characterized by an increased risk of thromboembolic events and also to a certain degree hypermetabolic symptoms. The gut microbiota is an important initiator of hematopoiesis and regulation of the immune system, but in patients with ET, where inflammation is a hallmark of the disease, it is vastly unexplored. In this study, we compared the gut microbiota via amplicon-based 16S rRNA gene sequencing of the V3-V4 region in 54 patients with ET according to mutation status Janus-kinase 2 ()-positive vs -negative patients with ET, and in 42 healthy controls (HCs). Gut microbiota richness was higher in patients with ET (median-observed richness, 283.5; range, 75-535) compared with HCs (median-observed richness, 191.5; range, 111-300; < 0.001). Patients with ET had a different overall bacterial composition (beta diversity) than HCs (analysis of similarities [ANOSIM]; = 0.063, = 0.004). Patients with ET had a significantly lower relative abundance of taxa within the phylum compared with HCs (51% vs 59%, = 0.03), and within that phylum, patients with ET also had a lower relative abundance of the genus (8% vs 15%, < 0.001), an important immunoregulative bacterium. The microbiota signatures were more pronounced in patients harboring the mutation, and highly similar to patients with polycythemia vera as previously described. These findings suggest that patients with ET may have an altered immune regulation; however, whether this dysregulation is induced in part by, or is itself inducing, an altered gut microbiota remains to be investigated. IMPORTANCE Essential thrombocythemia (ET) is a cancer characterized by thrombocyte overproduction. Inflammation has been shown to be vital in both the initiation and progression of other myeloproliferative neoplasms, and it is well known that the gut microbiota is important in the regulation of our immune system. However, the gut microbiota of patients with ET remains uninvestigated. In this study, we characterized the gut microbiota of patients with ET compared with healthy controls and thereby provide new insights into the field. We show that the gut microbiota of patients with ET differs significantly from that of healthy controls and the patients with ET have a lower relative abundance of important immunoregulative bacteria. Furthermore, we demonstrate that patients with -positive ET have pronounced gut microbiota signatures compared with -negative patients. Thereby confirming the importance of the underlying mutation, the immune response as well as the composition of the microbiota.
PubMed: 37695126
DOI: 10.1128/spectrum.00662-23 -
The glutaminase inhibitor CB-839 targets metabolic dependencies of JAK2-mutant hematopoiesis in MPN.Blood Advances May 2024Hyperproliferation of myeloid and erythroid cells in myeloproliferative neoplasms (MPN) driven by the JAK2-V617F mutation is associated with altered metabolism. Given...
Hyperproliferation of myeloid and erythroid cells in myeloproliferative neoplasms (MPN) driven by the JAK2-V617F mutation is associated with altered metabolism. Given the central role of glutamine in anabolic and catabolic pathways, we examined the effects of pharmacologically inhibiting glutaminolysis, that is, the conversion of glutamine (Gln) to glutamate (Glu), using CB-839, a small molecular inhibitor of the enzyme glutaminase (GLS). We show that CB-839 strongly reduced the mitochondrial respiration rate of bone marrow cells from JAK2-V617F mutant (VF) mice, demonstrating a marked dependence of these cells on Gln-derived ATP production. Consistently, in vivo treatment with CB-839 normalized blood glucose levels, reduced splenomegaly and decreased erythrocytosis in VF mice. These effects were more pronounced when CB-839 was combined with the JAK1/2 inhibitor ruxolitinib or the glycolysis inhibitor 3PO, indicating possible synergies when cotargeting different metabolic and oncogenic pathways. Furthermore, we show that the inhibition of glutaminolysis with CB-839 preferentially lowered the proportion of JAK2-mutant hematopoietic stem cells (HSCs). The total number of HSCs was decreased by CB-839, primarily by reducing HSCs in the G1 phase of the cell cycle. CB-839 in combination with ruxolitinib also strongly reduced myelofibrosis at later stages of MPN. In line with the effects shown in mice, proliferation of CD34+ hematopoietic stem and progenitor cells from polycythemia vera patients was inhibited by CB-839 at nanomolar concentrations. These data suggest that inhibiting GLS alone or in combination with inhibitors of glycolysis or JAK2 inhibitors represents an attractive new therapeutic approach to MPN.
Topics: Animals; Mice; Myeloproliferative Disorders; Janus Kinase 2; Hematopoiesis; Humans; Glutaminase; Benzeneacetamides; Mutation; Pyrimidines
PubMed: 38295283
DOI: 10.1182/bloodadvances.2023010950