Project description:Polycythemia vera (PV) is a slow-growing type of blood cancer, where the production of red blood cells (RBCs) increase considerably. The principal treatment for targeting the symptoms of PV is bloodletting (phlebotomy) at regular intervals based on data derived from blood counts and physician assessments based on experience. Model-based decision support can help to identify optimal and individualized phlebotomy schedules to improve the treatment success and reduce the number of phlebotomies and thus negative side effects of the therapy. We present an extension of a simple compartment model of the production of RBCs in adults to capture patients suffering from PV. We analyze the model's properties to show the plausibility of its assumptions. We complement this with numerical results using exemplary PV patient data. The model is then used to simulate the dynamics of the disease and to compute optimal treatment plans. We discuss heuristics and solution approaches for different settings, which include constraints arising in real-world applications, where the scheduling of phlebotomies depends on appointments between patients and treating physicians. We expect that this research can support personalized clinical decisions in cases of PV.

| S-EPMC7180210 | biostudies-literature

Generalized Chorea and JAK2V617F Mutation-Positive Myeloproliferative Disorders.

Project description: Not available

| S-EPMC7197301 | biostudies-literature

Differential cytokine network profile in polycythemia vera and secondary polycythemia.

Project description:Polycythemia vera (PV) is a clonal disorder resulting from neoplastic transformation of hematopoietic stem cells, while secondary polycythemia (SP) is a disease characterized by increased absolute red blood cell mass caused by stimulation of red blood cell production. Although the physiopathology of SP and PV is distinct, patients with these diseases share similar symptoms. The early differential diagnosis may improve the quality of life and decrease the disease burden in PV patients, as well as enable curative treatment for SP patients. PV is considered an oncoinflammatory disease because PV patients exhibit augmented levels of several pro-inflammatory cytokines. In this sense, we examined whether analysis of the cytokine production profile of SP and PV patients would help to distinguish them, despite their clinical similarities. Here we reported that SP patients exhibited decreased plasma levels of, IL-17A, IFN-γ, IL-12p70 and TNF-α when compared with PV patients, suggesting that analysis of the cytokine production profile may be an useful diagnostic biomarker to distinguish PV from SP patients.

| S-EPMC7468352 | biostudies-literature

No correlation of intensity of phlebotomy regimen with risk of thrombosis in polycythemia vera: evidence from European Collaboration on Low-Dose Aspirin in Polycythemia Vera and Cytoreductive Therapy in Polycythemia Vera clinical trials.

Project description: Not available

| S-EPMC5451347 | biostudies-literature

The impact of phlebotomy and hydroxyurea on survival and risk of thrombosis among older patients with polycythemia vera.

Project description:Current guidelines recommend therapeutic phlebotomy for all polycythemia vera (PV) patients and additional cytoreductive therapy (eg, hydroxyurea [HU]) for high-risk PV patients. Little is known about the impact of these therapies in the real-world setting. We conducted a retrospective cohort study of older adults diagnosed with PV from 2007 to 2013 using the linked Surveillance, Epidemiology, and End Results-Medicare database. Multivariable Cox proportional hazards models were used to assess the effect of phlebotomy and HU on overall survival (OS) and the occurrence of thrombotic events. Of 820 PV patients (median age = 77 years), 16.3% received neither phlebotomy nor HU, 23.0% were managed with phlebotomy only, 19.6% with HU only, and 41.1% with both treatments. After a median follow-up of 2.83 years, 37.2% (n = 305) of the patients died. Phlebotomy (yes/no; hazard ratio [HR] = 0.65; 95% confidence interval [CI], 0.51-0.81; P < .01), increasing phlebotomy intensity (HR = 0.71; 95% CI, 0.65-0.79; P < .01), and a higher proportion of days covered (PDC) by HU were all significantly associated with lower mortality. When thrombosis was the outcome of interest, phlebotomy (yes/no; HR = 0.52; 95% CI, 0.42-0.66; P < .01) and increasing phlebotomy intensity (HR = 0.46; 95% CI, 0.29-0.74; P < .01) were significantly associated with a lower risk of thrombotic events, so was a higher HU PDC. In this population-based study of older adults with PV reflecting contemporary clinical practice, phlebotomy and HU were associated with improved OS and decreased risk of thrombosis. However, both treatment modalities were underused in this cohort of older PV patients.

| S-EPMC6199652 | biostudies-literature

Acute normovolemic hemodilution for a patient with secondary polycythemia undergoing aortic valve replacement due to severe aortic stenosis - A case report.

Project description:BackgroundA high hematocrit level in patients with erythrocytosis is linked with increased blood viscosity and increased risk of thromboembolism. Therefore, it is necessary to adequately lower the hematocrit level before performing a high-risk surgery.CaseA 67-year-old male was scheduled for aortic valve replacement due to severe aortic stenosis. The preoperative hematocrit level of this patient was very high due to secondary polycythemia by hypoxia. We decided to perform acute normovolemic hemodilution after anesthetic induction to reduce the risk of thromboembolism in the patient. The patient was discharged after a successful surgery and a post-operative period without any side effects.ConclusionsWe estimate that patients with secondary polycythemia may benefit from acute normovolemic hemodilution to reduce their hematocrit levels while undergoing cardiac surgery using cardiopulmonary bypass. However, it is necessary to control the hematocrit level, since a significant decrease can cause side effects.

| S-EPMC7713815 | biostudies-literature

Aceruloplasminemia Presenting with Asymmetric Chorea Due to a Novel Frameshift Mutation.

Project description: Not available

| S-EPMC7525192 | biostudies-literature

A Patient with Congenital Generalized Lipodystrophy Due To a Novel Mutation in BSCL2: Indications for Secondary Mitochondrial Dysfunction.

Project description:BACKGROUND:Congenital generalized lipodystrophy (CGL) results from mutations in AGPAT2, encoding 1-acyl-glycerol-3-phosphate-acyltransferase 2 (CGL1; MIM 608594), BSCL2, encoding seipin (CGL2; MIM 269700), CAV1, encoding caveolin1 (CGL3; MIM 612526) or PTRF, encoding polymerase I and transcript release factor (CGL4; MIM 613327). This study aims to investigate the genotype/phenotype relationship and search for a possible pathogenic mechanism in a patient with CGL. DESIGN:Case report. PATIENTS AND SETTING:A 7-day-old child of consanguineous Turkish parents presented with a generalized loss of subcutaneous fat. He had a strikingly enlarged liver, high serum triglycerides, and hyperglycaemia, suggestive for CGL. RESULTS:A novel homozygous mutation in the acceptor splice site of exon 5 of the BSCL2 gene was found in the genome of the proband. This mutation causes a complex RNA splicing defect and results in two different aberrant seipin proteins, which were normally expressed and localized to the endoplasmic reticulum like wild type protein. Analysis of the patient's urine showed intermittent elevations of citric acid intermediates and persistently high concentrations of ethylmalonic acid, suggestive of a disturbance of the mitochondrial respiratory chain. CONCLUSION:Here we report abnormal urinary organic acid levels, indicative of mitochondrial dysfunction, in a patient with CGL resulting from a novel mutation in BSCL2. Our findings suggest for the first time an association between CGL and secondary mitochondrial dysfunction.

| S-EPMC3509903 | biostudies-literature

Chronic Kidney Disease has a Higher Prevalence in Polycythemia Vera than in Secondary Polycythemia, a Matched Case-Control Analysis.

Project description: Not available

| S-EPMC10542037 | biostudies-literature