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Medicina (Kaunas, Lithuania) Mar 2024: Several polymorphisms have been described in various DNA repair genes. Nucleotide excision DNA repair (NER) detects defects of DNA molecules and corrects them to...
: Several polymorphisms have been described in various DNA repair genes. Nucleotide excision DNA repair (NER) detects defects of DNA molecules and corrects them to restore genome integrity. We hypothesized that the , , , and gene polymorphisms influence the appearance of myeloproliferative neoplasms (MPNs). : We investigated the 1496C>T (rs2228000, Ala499Val), 2920A>C (rs228001, Lys939Gln), 2251A>C (rs13181, Lys751Gln), -673C>T (rs3136038), 11985A>G (rs254942), and 3507G>C (rs17655, Asp1104His) polymorphisms by polymerase chain reaction-restriction fragment length polymorphism analysis in 393 MPN patients [153 with polycythemia vera (PV), 201 with essential thrombocythemia (ET), and 39 with primary myelofibrosis (PMF)] and 323 healthy controls. : Overall, we found that variant genotypes of 2251A>C were associated with an increased risk of MPN (OR = 1.54, 95% CI = 1.15-2.08, = 0.004), while -673C>T and 11985A>G were associated with a decreased risk of developing MPN (OR = 0.56, 95% CI = 0.42-0.76, < 0.001; and OR = 0.26, 95% CI = 0.19-0.37, < 0.001, respectively). : In light of our findings, 2251A>C polymorphism was associated with the risk of developing MPN and -673C>T and 11985A>G single nucleotide polymorphisms (SNPs) may have a protective role for MPN, while 1496C>T, 2920A>C, and 3507G>C polymorphisms do not represent risk factors in MPN development.
Topics: Humans; DNA-Binding Proteins; Genetic Predisposition to Disease; Neoplasms; Polymorphism, Single Nucleotide; Genotype; DNA Repair
PubMed: 38541232
DOI: 10.3390/medicina60030506 -
Current Oncology (Toronto, Ont.) Mar 2024Neuroendocrine prostate cancer (NEPC) is a rare subtype of prostate cancer (PCa) that usually results in poor clinical outcomes and may be accompanied by paraneoplastic... (Review)
Review
Neuroendocrine prostate cancer (NEPC) is a rare subtype of prostate cancer (PCa) that usually results in poor clinical outcomes and may be accompanied by paraneoplastic syndromes (PNS). NEPC is becoming more frequent. It can initially manifest as PNS, complicating diagnosis. Therefore, we reviewed the literature on the different PNS associated with NEPC. We systematically reviewed English-language articles from January 2017 to September 2023, identifying 17 studies meeting PRISMA guidelines for NEPC and associated PNS. A total of 17 articles were included in the review. Among these, Cushing's Syndrome (CS) due to ectopic Adrenocorticotropic hormone (ACTH) secretion was the most commonly reported PNS. Other PNS included syndrome of inappropriate Anti-Diuretic Hormone secretion (SIADH), Anti-Hu-mediated chronic intestinal pseudo-obstruction (CIPO), limbic encephalitis, Evans Syndrome, hypercalcemia, dermatomyositis, and polycythemia. Many patients had a history of prostate adenocarcinoma treated with androgen deprivation therapy (ADT) before neuroendocrine features developed. The mean age was 65.5 years, with a maximum survival of 9 months post-diagnosis. NEPC is becoming an increasingly more common subtype of PCa that can result in various PNS. This makes the diagnosis and treatment of NEPC challenging. Further research is crucial to understanding these syndromes and developing standardized, targeted treatments to improve patient survival.
Topics: Male; Humans; Aged; Prostatic Neoplasms; Androgen Antagonists; Paraneoplastic Syndromes
PubMed: 38534956
DOI: 10.3390/curroncol31030123 -
Hematology Reports Mar 2024Factor VII (FVII) deficiency is a rare bleeding disorder that can be classified as congenital or acquired, and the majority of acquired cases are due to vitamin K...
Factor VII (FVII) deficiency is a rare bleeding disorder that can be classified as congenital or acquired, and the majority of acquired cases are due to vitamin K deficiency or liver disease. Isolated acquired FVII deficiency is a rare occurrence and has been associated with inhibitors or auto-antibodies. Here, we describe a patient with polycythemia vera who developed systemic mastocytosis and FVII deficiency simultaneously. FVII deficiency was not caused by inhibitors and improved with antineoplastic treatment. Acquired FVII deficiency has been reported in cases of sepsis, possibly due to proteolytic degradation induced by the activation of monocytes or endothelial cells. Malignancies have been shown to cause a depletion in circulating FVII through the direct binding of cancer cells. This case report suggests a potential association between SM associated with a hematological neoplasm (SM-AHN) and acquired FVII deficiency. Further evaluations are recommended in patients with systemic mastocytosis to gain a better understanding of the relationship between pathological mast cells and clotting factor concentrations.
PubMed: 38534884
DOI: 10.3390/hematolrep16010014 -
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 -
Frontiers in Oncology 2024Large cell neuroendocrine carcinoma (LCNEC) is a rare subtype of prostate cancer. The pathogenesis, clinical manifestation, treatment options, and prognosis are...
BACKGROUND
Large cell neuroendocrine carcinoma (LCNEC) is a rare subtype of prostate cancer. The pathogenesis, clinical manifestation, treatment options, and prognosis are uncertain and underreported.
MATERIALS AND METHODS
A systematic search was conducted in April 2022 through PubMed, Embase, and Cochrane. We reviewed cases of LCNEC developed either from or transformation from prostate adenocarcinoma and summarized the relevant pathophysiological course, treatment options, and outcomes.
RESULTS
A total of 25 patients with a mean age of 70.4 (range 43 87 years old) from 18 studies were included in this review. 13 patients were diagnosed with LCNEC of the prostate. 12 patients were from the transformation of adenocarcinoma post-hormonal therapy treatment. Upon initial diagnosis, patients diagnosed with prostatic LCNEC had a mean serum PSA value of 24.6 ng/ml (range: 0.09-170 ng/ml, median 5.5 ng/ml), while transformation cases were significantly lower at 3.3 ng/ml (range: 0-9.3 ng/ml, median 0.05 ng/ml). The pattern of metastasis closely resembles prostate adenocarcinoma. Six out of twenty-three cases displayed brain metastasis matching the correlation between neuroendocrine tumors and brain metastasis. Three notable paraneoplastic syndromes included Cushings syndrome, dermatomyositis, and polycythemia. Most patients with advanced metastatic disease received conventional platinum-based chemotherapy with a mean survival of 5 months. There was one exception in the transformation cohort with a somatic BRCA2 mutation who was treated with a combination of M6620 and platinum-based chemotherapy with an impressive PFS of 20 months. Patients with pure LCNEC phenotype have worse survival outcomes when compared to those with mixed LCNEC and adenocarcinoma phenotypes. It is unclear whether there is a survival benefit to administering ADT in pure pathologies.
CONCLUSION
LCNEC of the prostate is a rare disease that can occur or transformation from prostatic adenocarcinoma. Most patients present at an advanced stage with poor prognosis and are treated with conventional chemotherapy regimens. Patients who had better outcomes were those who were diagnosed at an early stage and received treatment with surgery or radiation and androgen deprivation therapy (ADT). There was one case with an exceptional outcome that included a treatment regimen of M6620 and chemotherapy.
PubMed: 38515575
DOI: 10.3389/fonc.2024.1341794 -
Revista Da Associacao Medica Brasileira... 2024This aim of this study was to evaluate hemoglobin and hematocrit values of polycythemia vera and secondary polycythemia patients with updated World Health Organization...
OBJECTIVE
This aim of this study was to evaluate hemoglobin and hematocrit values of polycythemia vera and secondary polycythemia patients with updated World Health Organization thresholds. In addition, by determining our own threshold values, we aimed to demonstrate the necessity of bone marrow biopsy and genetic analysis to be used for further diagnosis in patients with high-normal hematocrit and hemoglobin values.
METHODS
A cross-sectional and retrospective study was performed with the medical records of patients from Eskisehir City Hospital hematology clinics and outpatient clinics between July 1, 2019 and July 1, 2020. The study included patients with polycythemia, divided into two groups according to polycythemia vera and secondary polycythemia. A bone marrow biopsy was performed on patients with either Janus kinase mutation positivity and/or subnormal erythropoietin levels. Receiver operating characteristics analysis was used to find threshold values, and the diagnostic efficiency of these values in differentiating World Health Organization thresholds in 2008 and 2016 was evaluated.
RESULTS
A total of 73 patients were included. The median age was 43.5 years (min: 18; max: 84). The hematocrit value of 54.1 was predicted to diagnose polycythemia vera with a sensitivity of 45% and a specificity of 80%. Subsequent analysis revealed that an hemoglobin value of 17.7 was indicative of diagnosing polycythemia vera with a sensitivity of 60% and a specificity of 63%. The mean follow-up length was 6.4 months (2-12).
CONCLUSION
Our study demonstrated that modified World Health Organization criteria might lead to unnecessary additional tests for polycythemia vera patients with high-normal hemoglobin and hematocrit values.
Topics: Humans; Adult; Polycythemia Vera; Retrospective Studies; Polycythemia; Cross-Sectional Studies; Hemoglobins; Janus Kinase 2
PubMed: 38511749
DOI: 10.1590/1806-9282.20230497 -
Blood Advances May 2024Cytoreductive therapy is not routinely recommended for younger patients with polycythemia vera (PV) due to concern that treatment toxicity may outweigh therapeutic... (Meta-Analysis)
Meta-Analysis
Cytoreductive therapy is not routinely recommended for younger patients with polycythemia vera (PV) due to concern that treatment toxicity may outweigh therapeutic benefits. However, no systematic data support this approach. To support objective risk/benefit assessment of cytoreductive drugs in patients with PV aged <60 years (PV<60), this systematic review and meta-analysis was conducted to evaluate toxicity and disease-related complications in PV<60 treated with interferon alfa (rIFN-α) or hydroxyurea (HU). A search of PubMed, Scopus, Web of Science and Embase identified 693 unique studies with relevant keywords, of which 14 met inclusion criteria and were selected for analysis. The weighted average age of patients treated with rIFN-α was 48 years (n = 744 patients; 12 studies) and for HU was 56 years (n = 1397; 8 studies). The weighted average duration of treatment for either drug was 4.5 years. Using a Bayesian hierarchical model, the pooled annual rate of discontinuation due to toxicity was 5.2% for patients receiving rIFN-α (n = 587; 95% confidence interval [CI], 2.2-8.2) and 3.6% for HU (n = 1097; CI, 1-6.2). The average complete hematologic response for rIFN-α and HU was 62% and 52%, respectively. Patients experienced thrombotic events at a pooled annual rate of 0.79% and 1.26%; secondary myelofibrosis at 1.06% and 1.62%; acute myeloid leukemia at 0.14% and 0.26%; and death at 0.87% and 2.65%, respectively. No treatment-related deaths were reported. With acceptable rates of nonfatal toxicity, cytoreductive treatment, particularly with disease-modifying rIFN-α, may benefit PV<60. Future randomized trials prioritizing inclusion of PV<60 are needed to establish a long-term benefit of early cytoreductive treatment in these patients.
Topics: Humans; Polycythemia Vera; Treatment Outcome; Interferon-alpha; Hydroxyurea; Adult; Middle Aged; Cytoreduction Surgical Procedures; Age Factors
PubMed: 38507746
DOI: 10.1182/bloodadvances.2023012459 -
Journal of Cardiothoracic Surgery Mar 2024Morphologically, the risk of aortic aneurysm rupture is mainly evaluated based on its type (e.g., fusiform or saccular) and diameter. Based on the finite element...
BACKGROUND
Morphologically, the risk of aortic aneurysm rupture is mainly evaluated based on its type (e.g., fusiform or saccular) and diameter. Based on the finite element analysis, peak wall stress has been identified as a more sensitive and specific predictor of rupture in recent years. Moreover, in finite analysis, the neck of aneurysm is the highest peak wall stress and is associated with the rupture point.
CASE PRESENTATION
A saccular aortic aneurysm (84 mm) was incidentally detected during preoperative examination for chronic empyema in a 74-year-old male patient with a history of polycythemia. Aortic arch graft replacement using an open stent was performed.
CONCLUSIONS
Morphologically, this case was associated with a very high risk of rupture; nevertheless, it did not rupture. In this case, a mural thrombus (likely formed due to polycythemia) covered the neck of aneurysm that is experiencing the highest peak wall stress and is associated with the rupture point. The mural thrombus decreased peak wall stress and could reduce the risk of rupture even for huge saccular aneurysms. Furthermore, the mural thrombus was fully occupied in aneurysms, such as during coil embolization. Thus, polycythemia could decrease the risk of rupture of huge saccular aneurysms.
Topics: Male; Humans; Aged; Polycythemia; Aortic Aneurysm; Aortic Rupture; Thrombosis; Thromboembolism; Aortic Aneurysm, Abdominal
PubMed: 38491494
DOI: 10.1186/s13019-024-02645-7 -
Annals of Hematology Jun 2024Ruxolitinib is beneficial in patients with myelofibrosis (MF) and polycythemia vera (PV). Information on ruxolitinib adherence is scant. The Ruxolitinib Adherence in... (Clinical Trial)
Clinical Trial
Ruxolitinib is beneficial in patients with myelofibrosis (MF) and polycythemia vera (PV). Information on ruxolitinib adherence is scant. The Ruxolitinib Adherence in Myelofibrosis and Polycythemia Vera (RAMP) prospective multicenter study (NCT06078319) included 189 ruxolitinib-treated patients. Patients completed the Adherence to Refills and Medications Scale (ARMS) and Distress Thermometer and Problem List (DTPL) at the earliest convenience, after registration in the study, and at later timepoints. At week-0, low adherence (ARMS > 14) and high distress (DT ≥ 4) were declared by 49.7% and 40.2% of patients, respectively. The main reason for low adherence was difficult ruxolitinib supply (49%), intentional (4.3%) and unintentional (46.7%) non-take. In multivariable regression analysis, low adherence was associated to male sex (p = 0.001), high distress (p < 0.001), and treatment duration ≥ 1 year (p = 0.03). Over time, rates of low adherence and high distress remained stable, but unintentional non-take decreased from 47.9% to 26.0% at week-48. MF patients with stable high adherence/low distress were more likely to obtain/maintain the spleen response at week-24. Low adherence to ruxolitinib represents an unmet clinical need that require a multifaceted approach, based on reason behind it (patients characteristics and treatment duration). Its recognition may help distinguishing patients who are truly refractory and those in need of therapy optimization.
Topics: Humans; Primary Myelofibrosis; Nitriles; Pyrimidines; Pyrazoles; Male; Polycythemia Vera; Female; Prospective Studies; Aged; Middle Aged; Italy; Medication Adherence; Aged, 80 and over; Adult
PubMed: 38478023
DOI: 10.1007/s00277-024-05704-0 -
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