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Inflammation as a cause of acute myocardial infarction in patients with myeloproliferative neoplasm.World Journal of Cardiology Feb 2024Myeloproliferative neoplasms (MPN) are a group of diseases characterized by the clonal proliferation of hematopoietic progenitor or stem cells. They are clinically...
Myeloproliferative neoplasms (MPN) are a group of diseases characterized by the clonal proliferation of hematopoietic progenitor or stem cells. They are clinically classifiable into four main diseases: chronic myeloid leukemia, essential thrombocythemia, polycythemia vera, and primary myelofibrosis. These pathologies are closely related to cardio- and cerebrovascular diseases due to the increased risk of arterial thrombosis, the most common underlying cause of acute myocardial infarction. Recent evidence shows that the classical Virchow triad (hypercoagulability, blood stasis, endothelial injury) might offer an explanation for such association. Indeed, patients with MPN might have a higher number and more reactive circulating platelets and leukocytes, a tendency toward blood stasis because of a high number of circulating red blood cells, endothelial injury or overactivation as a consequence of sustained inflammation caused by the neoplastic clonal cell. These abnormal cancer cells, especially when associated with the JAK2V617F mutation, tend to proliferate and secrete several inflammatory cytokines. This sustains a pro-inflammatory state throughout the body. The direct consequence is the induction of a pro-thrombotic state that acts as a determinant in favoring both venous and arterial thrombus formation. Clinically, MPN patients need to be carefully evaluated to be treated not only with cytoreductive treatments but also with cardiovascular protective strategies.
PubMed: 38456066
DOI: 10.4330/wjc.v16.i2.58 -
Geburtshilfe Und Frauenheilkunde Mar 2024The aim of our study was to compare maternal, chorionicity and neonatal complications in monochorionic (MC) twins between spontaneously conceived (SC) and assisted...
INTRODUCTION
The aim of our study was to compare maternal, chorionicity and neonatal complications in monochorionic (MC) twins between spontaneously conceived (SC) and assisted reproductive technologies (ART) pregnancies.
MATERIAL AND METHODS
This was a retrospective cohort study between January 2010 to December 2019 at a tertiary referral University center. All consecutive pregnancies with MC twins that delivered at our University hospital were included. Maternal, chorionicity and neonatal complications were recorded and compared between SC and ART pregnancies.
RESULTS
393 MC pregnancies were included for final analysis, including 353 (89.8%) SC and 40 (10.2%) pregnancies conceived after ART. Hypothyroidism was the only maternal condition seen significantly more often in ART pregnancies (35.0% vs 12.5%, p = 0.001). There were no significant differences in chorionicity complications, such as twin-twin transfusion syndrome, selective fetal growth restriction and twin anemia-polycythemia sequence (40.0% in ART pregnancies vs 31.6% in SC pregnancies, p = 0.291). At least one congenital anomaly in one twin was seen significantly more often in ART pregnancies (18.8% vs 8.1%, p = 0.004), especially congenital heart defects (16.3% vs 6.2%, p = 0.005). There were no other significant differences in neonatal outcomes between both groups, however, there were non-significant trends in gestational age at delivery (34 weeks in ART pregnancies vs 35 weeks, p = 0.078) and birthweight (1951 g ± 747 in ART pregnancies vs 2143 g ± 579, p = 0.066).
CONCLUSION
This is the largest cohort study to date comparing maternal, chorionicity and neonatal complications between MC twin pregnancies after ART and after SC. Hypothyroidism was the only maternal condition occurring more frequently in pregnancies conceived after ART. There were no significant differences in chorionicity complications, in contrast to previously reported studies. While MC twins and ART pregnancies per se are known to be at risk for congenital heart defects, there seems to be a cumulative effect in MC pregnancies conceived after ART.
PubMed: 38455999
DOI: 10.1055/a-2238-3181 -
Cureus Feb 2024In a rare case, a 70-year-old female with polycythemia vera developed late-onset melanonychia, a seldom-documented side effect of hydroxyurea. Typically, melanonychia...
In a rare case, a 70-year-old female with polycythemia vera developed late-onset melanonychia, a seldom-documented side effect of hydroxyurea. Typically, melanonychia emerges within months of treatment, but this case is unique as it occurred four years into therapy. Notably, the patient, with darker skin, also had hyperpigmentation of her hands and tongue. Her history of hydroxyurea-associated ulcers and symptoms worsening with dose adjustment suggested drug involvement. While mucocutaneous hyperpigmentation from hydroxyurea is known, melanonychia and tongue hyperpigmentation are rarely reported, mostly in early treatment. This case highlights the importance of recognizing these side effects, especially in diverse populations and darker skin tones. The diverse skin tones seen in Sub-Saharan Africa add complexity to diagnosing such dermatological conditions, highlighting the need for awareness. Melanonychia can mimic severe conditions such as subungual melanoma, emphasizing the significance of accurate recognition and management without invasive tests. Educating clinicians and patients about these benign drug-related phenomena is essential for precise identification and management. This case contributes to understanding late-onset hydroxyurea-induced melanonychia and tongue hyperpigmentation, enhancing clinical knowledge in diverse populations.
PubMed: 38449930
DOI: 10.7759/cureus.53642 -
BMC Pulmonary Medicine Mar 2024Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide among people over 40 years of age, and erythrocytosis is one of the major...
BACKGROUND
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide among people over 40 years of age, and erythrocytosis is one of the major complications associated with increased mortality among COPD patients. The study aimed to determine the proportion of COPD, associated factors, and the burden of erythrocytosis among COPD participants.
METHODS AND MATERIALS
A descriptive cross-sectional study design was used. A consecutive sampling technique was used to obtain study participants at the Fort Portal Regional Referral Hospital outpatient clinic. Focused history and physical examination were carried out to select eligible participants. Participants were screened using the COPD population screener for spirometry after consenting to participate. The study enrolled all adults at risk of having COPD based on the COPD population screener and able to undergo spirometry. Spirometry was carried out according to the Global Chronic Obstructive Lung Disease and European Respiratory Society guidelines, and haemoglobin concentration was measured.
RESULTS
One hundred eighty participants were enrolled in the study, most of whom were females. The modal and mean age of participants was 60 years with 139 (77.2%) females and primary as the highest education level 149(82.8%). The proportion of COPD was 25% (45) [95% CI 18.9 - 32] and highest among females (68.9%) and those aged 60 years and above (70%). The combined COPD assessment tool groups had a proportion of 55.6%, 37.8%, 4.4%, and 2.2% for groups A, B, C, and D, respectively. Age < 50 years was protective against COPD, while for every additional year of smoking, there was an associated 6.5% increased risk compared to the general population. Additionally, the proportion of erythrocytosis among COPD participants was 6.7%.
CONCLUSIONS AND RECOMMENDATIONS
There was a high proportion of COPD among study participants (25%), with a 6.7% proportion of erythrocytosis. We recommend a complete blood count for every patient in groups C and D of the ABCD COPD GOLD groups.
Topics: Adult; Female; Humans; Middle Aged; Male; Tertiary Care Centers; Polycythemia; Cross-Sectional Studies; Uganda; Pulmonary Disease, Chronic Obstructive
PubMed: 38448860
DOI: 10.1186/s12890-024-02944-8 -
Kidney & Blood Pressure Research 2024Cyanotic nephropathy, a rare disease characterized by proteinuria, decreased estimated glomerular filtration rate, thrombocytopenia, polycythemia, and hyperuricemia, may... (Review)
Review
INTRODUCTION
Cyanotic nephropathy, a rare disease characterized by proteinuria, decreased estimated glomerular filtration rate, thrombocytopenia, polycythemia, and hyperuricemia, may occasionally be secondary to cyanotic congenital heart disease (CHD). There are currently no detailed diagnostic criteria or treatments for cyanotic nephropathy, owing to its extremely low incidence. Eisenmenger syndrome (ES) was initially defined by Paul Wood in pathophysiologic terms as "pulmonary hypertension (PH) at the systemic level, caused by a high pulmonary vascular resistance, with a reversed or bidirectional shunt at the aorto-pulmonary, ventricular, or atrial level." It typically develops in the presence of large, unrepaired atrial or ventricular septal defects, arterial shunts, or complex forms of CHD and is the most severe hemodynamic phenotype of pulmonary arterial hypertension associated with CHD. This study aimed to outline the case of an ES patient who developed cyanotic nephropathy and successfully achieved clinical remission through primary disease treatment and symptomatic management. Overall, this case expands our understanding of cyanotic nephropathy and lays a theoretical reference for the treatment of ES.
CASE PRESENTATION
A 33-year-old Chinese female attended the outpatient department with abnormal urine test results over the past two and a half years. Following a comprehensive medical history collection, she underwent the necessary tests. Cardiac color ultrasound displayed a significant widening of the pulmonary artery and PH (severe), as well as mild tricuspid regurgitation and patent ductus arteriosus. The results of the kidney biopsy, combined with clinical findings, suggested a high risk of polycythemia-related kidney disease. She was eventually diagnosed with cyanotic nephropathy and ES. Her symptoms were relieved following symptomatic treatment, such as the administration of ambrisentan, febuxostat, and home oxygen therapy. Her follow-up visit at 6 months demonstrated improvements in hyperuricemia and a significant increase in physical strength.
CONCLUSION
Cyanotic nephropathy is a rare condition in adults. Kidney biopsy remains the gold standard of diagnosis for various nephropathies. Active treatment of CHD and alleviating hypoxia may be pivotal for the treatment of cyanotic nephropathy.
Topics: Humans; Female; Adult; Eisenmenger Complex; Kidney Diseases; Cyanosis; Polycythemia
PubMed: 38447536
DOI: 10.1159/000538100 -
Neurology India Jan 2024
Topics: Humans; Polycythemia
PubMed: 38443036
DOI: 10.4103/NI.Neurol-India-D-23-00612 -
European Review For Medical and... Feb 2024Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominantly inherited cerebral small vessel disease...
BACKGROUND
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal dominantly inherited cerebral small vessel disease caused by Neurogenic locus notch homolog protein 3 (NOTCH3) gene mutations. The main clinical features include migraine with aura, recurrent ischemic strokes and dementia. Brain MRI typically shows multiple small lacunar infarcts and severe, diffuse, symmetrical white matter hyperintensities (WMHs), with characteristic involvement of the anterior temporal pole, external capsule, and superior frontal gyrus. Reports of twins with CADASIL are scarce. Herein we describe a pair of monozygotic twins with peculiar CADASIL phenotype, carrying a new NOTCH3 variant.
CASE PRESENTATION
Twin A was a 45-year-old male suffering from migraine, obesity, arterial hypertension, and polycythemia (with negative genetic analysis), who complained of a transient, short-lasting (~ 5 minutes) episode of speech difficulties. Brain MRI showed diffuse, symmetrical, confluent periventricular WMHs involving frontal, parietal, and temporal lobes and external capsules, with sparing of anterior temporal poles. Genetic analysis of NOTCH3 gene demonstrated the presence of missense c.3329G>A, p.(Cys1110Tyr) variant, confirming CADASIL diagnosis. Twin B, affected by migraine and polycythemia, as well as his monozygotic twin, presented with a 2-month history of trigeminal neuralgia. Brain MRI demonstrated diffuse WMHs with a pattern of distribution like his twin. Genetic analysis revealed the same NOTCH3 pathogenic variant.
CONCLUSIONS
Our monozygotic twins have a strikingly similar neuroimaging picture with sparing of anterior temporal poles. They also have a peculiar phenotype, both presenting polycythemia without genetically confirmed cause. Twin B had trigeminal neuralgia, that is unusual in CADASIL. The possible association of the peculiar findings with the newly reported NOTCH3 variant needs to be confirmed with further observations.
Topics: Male; Humans; Middle Aged; Twins, Monozygotic; CADASIL; Polycythemia; Receptor, Notch3; Trigeminal Neuralgia; Migraine Disorders
PubMed: 38436192
DOI: 10.26355/eurrev_202402_35489 -
Frontiers in Physiology 2024High-altitude polycythemia (HAPC) is a common chronic high-altitude disease characterized by significantly increased erythrocyte, hemoglobin (Hb), and hematocrit values...
High-altitude polycythemia (HAPC) is a common chronic high-altitude disease characterized by significantly increased erythrocyte, hemoglobin (Hb), and hematocrit values and decreased arterial oxygen saturation. The mechanisms underlying HAPC development are unclear; we aimed to investigate this in an HAPC rat model. Twelve Sprague-Dawley rats were divided into control and HAPC groups. The HAPC group was exposed to hypobaric hypoxia. This HAPC model was assessed using routine blood tests and blood gas analyses. Bone marrow, peripheral blood reticulocytes (RETs), and peripheral blood erythrocyte apoptosis were measured using flow cytometry. Erythrocyte osmotic fragility (EOF) tests were conducted. Abnormal erythrocytes were counted using electron microscopy. Plasma-free hemoglobin, 5'-nucleotidase (CD73), adenosine, erythrocyte cytosolic adenosine, sphingosine-1-phosphate (S1P), and 2,3-bisphosphoglycerate (BPG) levels were measured using enzyme-linked immunosorbent assays. Erythrocyte metabolic pathway-related protein [adenosine A2B receptor (ADORA2B), erythrocyte equilibrative nucleoside transporter 1 (eENT1), sphingosine kinase 1 (SPHK1), phospho-SPHK1, bisphosphoglycerate mutase (BPGM), and glyceraldehyde 3-phosphate dehydrogenase (GAPDH)] levels were assessed by Western blotting. The HAPC rat model was successfully established (Hb > 210 g/L). Indices of bone marrow and peripheral blood RET proportions were significantly higher in the HAPC than the control group ( = 0.04 and < 0.001, respectively). The proportion of peripheral blood erythrocytes in early apoptosis was significantly lower in the HAPC than the control group ( < 0.001). Vesicular erythrocyte and acanthocyte proportions were significantly higher in the HAPC than the control group ( < 0.001 and = 0.019, respectively). The EOF tests revealed that 50% erythrocyte hemolysis occurred at 4.0-4.5 and 4.5-5.0 g/L NaCl in the control and HAPC groups, respectively. Plasma-free hemoglobin, CD73, adenosine, erythrocyte cytosolic adenosine, S1P, and 2,3-BPG levels and ADORA2B, eENT1, phospho-SPHK1, S1P, BPGM, and GAPDH erythrocyte expression levels (all ≤ 0.02) were significantly higher in the HAPC than the control group. In model rats, an HAPC-related erythrocyte increase was associated with enhanced bone marrow hematopoietic function and reduced erythrocyte apoptosis, whereas numerous abnormal erythrocytes, increased EOF, and reduced hemolysis resistance were associated with erythrocyte metabolism. CD73/adenosine/S1P/2,3-BPG and eENT1/adenosine/BPGM/2,3-BPG metabolic pathways in erythrocytes were activated in HAPC rats, facilitating oxygen release. These findings further reveal the intrinsic HAPC mechanism and forms a basis for future development of preventive and therapeutic strategies for HAPC.
PubMed: 38426208
DOI: 10.3389/fphys.2024.1359357 -
Communications Biology Feb 2024Pacak-Zhuang syndrome is caused by mutations in the EPAS1 gene, which encodes for one of the three hypoxia-inducible factor alpha (HIFα) paralogs HIF2α and is...
Pacak-Zhuang syndrome is caused by mutations in the EPAS1 gene, which encodes for one of the three hypoxia-inducible factor alpha (HIFα) paralogs HIF2α and is associated with defined but varied phenotypic presentations including neuroendocrine tumors and polycythemia. However, the mechanisms underlying the complex genotype-phenotype correlations remain incompletely understood. Here, we devised a quantitative method for determining the dissociation constant (K) of the HIF2α peptides containing disease-associated mutations and the catalytic domain of prolyl-hydroxylase (PHD2) using microscale thermophoresis (MST) and showed that neuroendocrine-associated Class 1 HIF2α mutants have distinctly higher K than the exclusively polycythemia-associated Class 2 HIF2α mutants. Based on the co-crystal structure of PHD2/HIF2α peptide complex at 1.8 Å resolution, we showed that the Class 1 mutated residues are localized to the critical interface between HIF2α and PHD2, adjacent to the PHD2 active catalytic site, while Class 2 mutated residues are localized to the more flexible region of HIF2α that makes less contact with PHD2. Concordantly, Class 1 mutations were found to significantly increase HIF2α-mediated transcriptional activation in cellulo compared to Class 2 counterparts. These results reveal a structural mechanism in which the strength of the interaction between HIF2α and PHD2 is at the root of the general genotype-phenotype correlations observed in Pacak-Zhuang syndrome.
Topics: Humans; Prolyl Hydroxylases; Hydroxylation; Polycythemia; Mutation; Procollagen-Proline Dioxygenase
PubMed: 38418569
DOI: 10.1038/s42003-024-05904-4