ABSTRACT
The manuscript provides an overview of treatment and its changes in adult patients with haemophilia A without inhibitors in the Czech Republic between 2013 and 2021 using data from the registry of the Czech National Haemophilia Programme (CNHP). Over a 9-year period, we focused on the reduction in the annual bleeding rate (ABR), joint bleeding rate (AJBR) and factor VIII consumption when patients with severe haemophilia A switched from on-demand treatment to prophylaxis. The ABR and AJBR include both patient-reported home treatment and treated hospitalisation episodes. All adult patients with severe haemophilia A were categorised into three groups according to the therapeutic regimen. The first group was patients on prophylaxis during the follow-up period, the second group consisted of patients on on-demand treatment, and the third group was patients who received both treatment regimens during follow-up. With an increase in the proportion of patients with severe haemophilia A on prophylaxis from 37 to 74% between 2013 and 2021, the ABR for all patients with severe haemophilia A decreased approximately 6.9-fold, and the AJBR decreased 8.7-fold. Expectedly, the factor consumption increased by approximately 68.5%. In the group of patients with severe haemophilia A who had switched from an on-demand to a prophylactic regimen, the total number of bleeding events decreased 3.5-fold, and the number of joint bleeding episodes decreased 3.9-fold. Factor VIII consumption increased by 78.4%. Our study supports a previously reported positive effect of prophylaxis on bleeding control. We believe that the substantial improvement in ABR justifies the increased treatment costs.
ABSTRACT
Antiphosholipid syndrome (APS) is defined by the presence of clinical and laboratory criteria, it means by presence of antiphospholipid antibodies. Venous thromboembolism belongs to the most frequent clinical manifestation of this syndrome. Here we summarised basic pathophysiological mechanisms of venous thrombosis and lung embolism development, epidemiology of APS, and also the situations when this syndrome should be considered. The possible difficulties of laboratory diagnosis and their therapy involvement are mentioned.
Subject(s)
Antiphospholipid Syndrome , Pulmonary Embolism , Venous Thromboembolism , Venous Thrombosis , Humans , Antiphospholipid Syndrome/complications , Venous Thromboembolism/drug therapy , Antibodies, AntiphospholipidABSTRACT
Plasma cell leukaemia (PCL) is a rare and very aggressive plasma cell disorder. Preventing a dismal outcome of PCL requires early diagnosis with appropriate analytical tools. Therefore, the investigation of 33 patients with primary and secondary PCL was done when the quantity of circulating plasma cells (PCs) using flow cytometry (FC) and morphology assessment was evaluated. The phenotypic profile of the PCs was also analysed to determine if there is an association with clinical outcomes and to evaluate the prognostic value of analysed markers. Our results revealed that FC is an excellent method for identifying circulating PCs as a significantly higher number was identified by FC than by morphology (26·7% vs. 13·5%, P = 0·02). None of secondary PCL cases expressed CD19 or CD20. A low level of expression with similar positivity of CD27, CD28, CD81 and CD117 was found in both PCL groups. A decrease of CD44 expression was detected only in secondary PCL. Expression of CD56 was present in more than half of PCL cases as well as cytoplasmic nestin. A decreased level of platelets, Eastern Cooperative Oncology Group score of 2-3 and lack of CD20+ PC were associated with a higher risk of death. FC could be incorporated in PCL diagnostics not only to determine the number of circulating PCs, but also to assess their phenotype profile and this information should be useful in patients' diagnosis and possible prognosis.
Subject(s)
Blood Cell Count , Flow Cytometry/methods , Leukemia, Plasma Cell/blood , Neoplastic Cells, Circulating , Plasma Cells , Adult , Aged , Aged, 80 and over , Antigens, CD/analysis , Antigens, Neoplasm/analysis , Blood Cell Count/methods , Bone Marrow/pathology , Bone Marrow Cells/chemistry , Early Detection of Cancer , False Negative Reactions , Female , Humans , Immunophenotyping , Kaplan-Meier Estimate , Leukemia, Plasma Cell/mortality , Male , Middle Aged , Plasma Cells/chemistry , Plasma Cells/ultrastructure , Progression-Free SurvivalABSTRACT
Arterial thrombosis is a common complication in patients with Ph- myeloproliferative neoplasms (MPN). We searched for the risk factors of stroke in MPN patients from anagrelide registry. We analyzed the potential risk factors triggering a stroke/TIA event in 249 MPN patients with previous stroke (n = 168) or Transient Ischemic Attack (TIA) (n = 140), and in 1,193 MPN control subjects (without clinical history of thrombosis). These patients were registered in a prospective manner, providing a follow-up period after Anagrelide treatment. The median age of the patients in the experimental group was of 56 years of age (ranging from 34-76) and of 53 years of age (ranging from 26-74) in the control group (p < 0.001). Using a multivariate model, we determined the following as risk factors: JAK2V617F mutation (OR 2.106, 1.458-3.043, p = 0.006), age (OR 1.017/year, 1.005-1,029, p = 0.006), male gender (OR 1.419, 1.057-1.903, p = 0.020), MPN diagnosis (OR for PMF 0.649, 0.446-0.944, p = 0.024), BMI (OR 0.687 for BMI > 25, 0.473-0.999, p = 0.05) and high TAG levels (OR 1.734, 1.162-2.586, p = 0.008), all of which were statistically significant for CMP development. Concerning the risk factors for thrombophilia, only the antiphospholipid syndrome (OR 1.994, 1.017-3.91, p = 0.048) was noteworthy in a stroke-relevant context. There was no significant difference between the blood count of the patients prior to a stroke event and the control group, both of which were under a cytoreductive treatment. We found that age, male gender, JAK2V617F mutation, previous venous thrombosis, and hypertriglyceridemia represent independent risk factors for the occurrence of a stroke in Ph- MPN patients.
Subject(s)
Fibrinolytic Agents/therapeutic use , Myeloproliferative Disorders/complications , Quinazolines/therapeutic use , Stroke/etiology , Thrombosis/prevention & control , Adult , Aged , Female , Humans , Janus Kinase 2/genetics , Male , Middle Aged , Myeloproliferative Disorders/genetics , Risk Factors , Thrombosis/etiologyABSTRACT
Thrombosis is the most common complication in BCR-ABL1 negative myeloproliferative neoplasms (MPN) that significantly impacts patients' mortality. Generally, there is an agreement on risk factors that possibly contribute to the increased risk of thrombosis, including age, history of thrombosis, JAK2V617F mutation, and cardiovascular risk factors. This study retrospectively investigates MPN-related and patient-related variables in relation to the thrombosis occurrence in MPN. Our analyses show that JAK2V617F-mutated patients are at a significantly increased risk of thrombosis within five years before the MPN diagnosis point with a hazard ratio (HR) of 15.49 (p=0.006). In multivariate analyses, independent risk factors for thrombotic complications during the follow-up are history of thrombosis (HR=2.23, p=0.019), age over 60 years at diagnosis (HR=1.56, p=0.037), the presence of JAK2V617F mutation (HR=3.01, p=0.002), and tobacco smoking (HR=1.75, p=0.01). Our results support the multifactorial mechanism of thrombosis in MPN patients, which demands individual and complex management.
Subject(s)
Neoplasms , Thrombosis , Humans , Janus Kinase 2/genetics , Middle Aged , Mutation , Retrospective Studies , Risk Factors , Thrombosis/geneticsABSTRACT
There is insufficient evidence from medical studies for clinical approaches to patients with COVID-19 in primary care. Patients often urge the therapeutic use and preventive administration of various medicines, often controlled by studies insufficiently or completely unverified. The aim of the project, commissioned by the Committee of the Society of General Practice of the Czech Medical Association JEP, was to compensate for this deficiency by interdisciplinary consensus and thus provide general practitioners (GPs) with a basic support in accessing patients with COVID-19. Representatives of GPs identified the most common questionable diagnostic or therapeutic approaches and formulated 17 theses, taking into account their own experience, existing Czech and foreign professional recommendations. The RAND/UCLA Appropriateness Method, modified for the needs of pandemic situation, was chosen to seek consensus. Representatives of 7 medical specialties accepted the participation in the 20-member panel. The panel evaluated in 2 rounds, with the comments and opinions of others available to all panelists before the second round. The outcome of the evaluation was agreement on 10 theses addressing the administration of vitamin D, inhaled corticosteroids in patients with COPD and bronchial asthma, acetylsalicylic acid, indications for D-dimer levels examination, preventive administration of LMWH, importance of pulse oximetry, indication for emergency services, indication for antibiotics and rules for distant contact. The panel disagreed on 6 theses recommending the administration of ivermectin, isoprinosine, colchicine and corticosteroids in patients with COVID-19 in primary care. One thesis, taking into account the use of D-dimers in primary care was evaluated as uncertain. The most discussed theses, on which there was also no agreement, were outpatient administration of corticosteroids and the importance of elevation of D-dimers levels or their dynamic increase in a symptomatic patient with COVID-19 as an indication for referral to hospital. The results of the consensus identified topics that need to be further discussed and on which it is appropriate to focus further research.
Subject(s)
COVID-19 , Chronic Disease , Heparin, Low-Molecular-Weight , Humans , Primary Health Care , SARS-CoV-2ABSTRACT
Pembrolizumab belongs to so called immune checkpoint inhibitors. Frequent adverse event of this therapy is hypothyroidism. The authors present a case report of patient treated with pembrolizumab for non-small cell lung carcinoma, in whom severe hypothyroidism followed quite rapidly after transient phase of subclinical hyperthyroidism - at this time point new and spontaneous onset of large subcutaneous hematomas was observed. Acquired von Willebrand syndrome, acquired hemophilia A, dysfibrinogenemia, activation of fibrinolysis and thrombocytopathy were all actively ruled out in hematological differential diagnosis. Concomittantly, laboratory markers of secondary autoimmune disease and myositis were excluded. Despite continuous pembrolizumab treatment, there were no other bleeding complications seen after intensification of endocrine substitution therapy with thyroid hormones. Causal relationship between subcutaneous hematomas and severe drug-induced hypothyroidism is established per exclusionem.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Hypothyroidism , Lung Neoplasms , Antibodies, Monoclonal, Humanized , HumansABSTRACT
The authors present a case report of 59-years-old woman examined for pancytopenia recently diagnosed during hospitalization for bilateral interstitial pneumonia without any confirmed etiological agents. Concomitantly, some systemic symptoms like lack of appetite and weight loss were present. Primary hematological disease was ruled out. Positivity of serological screening for HIV-1,2 was rather surprising. Absolute count of CD4+ lymphocytes was 8/μl. Thus, HIV infection was already in stage of AIDS and retrospectively, the interstitial pneumonia has to be judged as AIDS-indicative illness.
Subject(s)
Acquired Immunodeficiency Syndrome , HIV Infections , Pancytopenia , Acquired Immunodeficiency Syndrome/complications , CD4-Positive T-Lymphocytes , Female , HIV Infections/complications , Humans , Middle Aged , Pancytopenia/etiology , Retrospective StudiesABSTRACT
INTRODUCTION: Critically ill patients are exposed to a high risk of developing thromboembolism. Moreover, standard prophylaxis with subcutaneous (SC) heparin is less efficient in patients requiring vasopressors. The aim is a comparison of pharmacokinetics between SC and intravenous (IV) applied nadroparin. METHODS: Thirty-eight ventilated ICU patients requiring vasopressor support were randomized into a single dose of nadroparin 3,800 IU (0.4 mL) subcutaneously (SC group) or 1,900 IU (0.2 mL) intravenously (IV group). Anti-factor Xa activity (anti-Xa) was observed over 24 h; data are stated as median (IQR). RESULTS: Peak anti-Xa was significantly higher in the IV group 0.42 (0.39-0.43) IU/mL than in the SC group 0.16 (0.09-0.18) IU/mL (p < 0.001). There was a trend towards higher area under the curve (AUC) of anti-Xa in the SC group 1.41 (0.41-1.80) IU/mL × h than in the IV group 1.04 (0.93-1.13) IU/mL × h (p = 0.08). In the SC group, there was a negative correlation between anti-Xa AUC and both capillary refill time Xa (r = -0.86) and norepinephrine dose (r = -0.68). In the IV group, anti-Xa decrease half-life was 1.6 (1.4-2.0) h. CONCLUSIONS: IV administration of 1,900 IU of nadroparin led to a predictable effective peak anti-Xa. After SC administration, anti-Xa was heterogeneous and significantly influenced by peripheral perfusion.
Subject(s)
Anticoagulants/pharmacokinetics , Nadroparin/pharmacokinetics , Administration, Intravenous , Aged , Anticoagulants/administration & dosage , Critical Illness , Factor Xa/analysis , Female , Humans , Injections, Subcutaneous , Male , Middle Aged , Nadroparin/administration & dosage , Vasoconstrictor Agents/therapeutic use , Venous Thromboembolism/prevention & controlABSTRACT
The authors present clinical case of orthotopic liver transplantation for cirhosis due to chronic viral hepatitis C in a subject with severe hemophilia A. Preoperatively performed pharmacokinetic study with recombinant F VIII confirmed satisfactory in vivo recovery of 2.1 %. A bolus application of 52 units F VIII/kg body weight with target F VIII activity over 100.0 % was administred shortly before the transplantation started. Totally, 30 000 units of recombinant F VIII, 3 thrombocyte concentrates, 2 erythrocyte concentrates, 5 units of virally inactivated plasma, 1 unit of fresh frozen plasma and 3 500 antithrombin units were used. There were no perioperative or postoperative bleeding complications, F VIII substitution was stopped on postoperative day 3. The patient was discharged on twentieth postoperative day.
Subject(s)
Hemophilia A , Liver Transplantation , Factor VIII , Hemophilia A/complications , HumansABSTRACT
Heparin-induced thrombocytopenia (HIT) is an immunologically-mediated complication, which usually follows heparin exposition, less frequently exposition to other drugs or even occurs spontaneously. The type of heparin, its dose and mode of application as well as the exposition time, major trauma or operation, and obesity represent the main risk factors for HIT. The probability of HIT correlates with so-called 4T-score. A confirmatory laboratory diagnostic should be exclusively reserved for patients with a medium to a high probability of HIT development (more than 3 points in 4T-score). The screening method is based on serological detection of antibodies against heparin-platelet factor-4 complexes; confirmation tests aim to identify the activation of platelets. The treatment of HIT requires an immediate interruption of heparin application and rigorous antithrombotic treatment with an alternative agent. Herein authors describe a clinical case of HIT manifested as an extreme urticarial reaction in the location of nadroparin application as well as thrombosis of deep subcutaneous veins in a polymorbid obese patient with an extensive and infected burn. Due to timely diagnosis and fondaparinux treatment, no more severe thrombotic events occurred in this patient.
Subject(s)
Thrombocytopenia , Thrombosis , Anticoagulants/adverse effects , Fondaparinux , Heparin/adverse effects , Humans , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosisABSTRACT
Panhypopituitarism following craniopharyngioma resection has systemic impact with potential influence on physio-logical hematopoiesis. There is a growing body of evidence of liver fibrosis/cirrhosis risk development due to altered metabolism and lipid accumulation. The authors present a case report of a woman with a history of craniopharyngioma resection followed by aggravating pancytopenia with suspected indolent lymphoproliferative disorder and possible acquired bone marrow aplasia syndrome due to paroxysmal nocturnal hemoglobinuria. A complex hemostasis disorder with deficiency of multiple coagulation factors (FXII, FXI, FX, FIX, FVII, FX, FV, FXIII, antitrombin, protein C, protein S) was accidentally detected. Despite normal sonographic liver imaging, all possible causes of chronic liver disease were systematically excluded (viral hepatitis, hemochromatosis, Wilson´s disease, α-1-antitrypsin deficiency); anti-LKM-1 and anti-ENA antibodies were detected. Finally, the magnetic resonance imaging confirmed image of liver cirrhosis - with signs of portal hypertension.
Subject(s)
Craniopharyngioma/surgery , Hypopituitarism/etiology , Liver Cirrhosis/etiology , Neurosurgical Procedures/adverse effects , Pancytopenia/etiology , Pituitary Neoplasms/surgery , Blood Coagulation Factors , Female , HumansABSTRACT
Multiple myeloma is the second most common hematological malignancy characterized by focal lesions of malignant plasma cells in the bone marrow. These lesions contain subclones that directly influence survival of patients. Bone marrow biopsies are single-site biopsies and thus cannot contain all information about the tumor. In contrast, liquid biopsies analyze circulating cells and molecules that are secreted from all sites of the tumor. Long noncoding RNA molecules are one class of these molecules. We performed a two-phase biomarker study investigating lncRNA expression profiles in exosomes of peripheral blood serum of newly diagnosed multiple myeloma (MM) patients, monoclonal gammopathy of undetermined significance (MGUS) patients in comparison with healthy donors (HD). Surprisingly, this analysis revealed dysregulation of only one exosomal lncRNA PRINS in MM vs HD. Overall, MM and MGUS patients were distinguished from HD with sensitivity of 84.9% and specificity of 83.3%. Our study suggests a possible diagnostic role for exosomal lncRNA PRINS in monoclonal gammopathies patients.
Subject(s)
Exosomes/metabolism , Multiple Myeloma , RNA, Long Noncoding/blood , RNA, Neoplasm/blood , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Female , Humans , Male , Middle Aged , Multiple Myeloma/blood , Multiple Myeloma/diagnosis , Multiple Myeloma/mortality , Survival RateABSTRACT
OBJECTIVES: To present the Central European Myeloproliferative Neoplasm Organisation (CEMPO) treatment recommendations for polycythaemia vera (PV). METHODS: During meetings held from 2015 through 2017, CEMPO discussed PV and its treatment and recent data. RESULTS: PV is associated with increased risks of thrombosis/thrombo-haemorrhagic complications, fibrotic progression and leukaemic transformation. Presence of Janus kinase (JAK)-2 gene mutations is a diagnostic marker and standard diagnostic criterion. World Health Organization 2016 diagnostic criteria for PV, focusing on haemoglobin levels and bone marrow morphology, are mandatory. PV therapy aims at managing long-term risks of vascular complications and progression towards transformation to acute myeloid leukaemia and myelodysplastic syndrome. Risk stratification for thrombotic complications guides therapeutic decisions. Low-risk patients are treated first line with low-dose aspirin and phlebotomy. Cytoreduction is considered for low-risk (phlebotomy intolerance, severe/progressive symptoms, cardiovascular risk factors) and high-risk patients. Hydroxyurea is suspected of leukaemogenic potential. IFN-α has demonstrated efficacy in many clinical trials; its pegylated form is best tolerated, enabling less frequent administration than standard interferon. Ropeginterferon alfa-2b has been shown to be more efficacious than hydroxyurea. JAK1/JAK2 inhibitor ruxolitinib is approved for hydroxyurea resistant/intolerant patients. CONCLUSIONS: Greater understanding of PV is serving as a platform for new therapy development and treatment response predictors.
ABSTRACT
Over the last 10 years some new drugs affecting blood clotting - antithrombotics - were invented. For more than half a century only warfarin and heparin were available. A better understanding of the pathways involved in activation of blood clotting, the links between these systems, and the impact of thrombosis on inflammation, have led to identification of new targets and development of new drugs, especially new antiplatelet drugs and anticoagulants. With the advent of new drugs into clinical practice, treatment options of thrombotic complications are expanding. However, it is always necessary to get familiar with the drug and its properties and to know its limitations. This is the only way to offer patients the best practices. Key words: anticoagulant - antithrombotic - Direct Oral AntiCoagulant (DOAC) - laboratory monitoring - Low-Molecu-lar-Weight Heparins (LMWH) - New Oral Anticoagulants/Non-vitamin K Oral AntiCoagulants (NOAC) - unfractionated heparin (UFH) - warfarin.
Subject(s)
Anticoagulants , Anticoagulants/therapeutic use , Fibrinolytic Agents/therapeutic use , Heparin/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Warfarin/therapeutic useABSTRACT
Well-managed warfarin therapy remains an important method of anticoagulation in the 21st century, despite the introduction of new antithrombotics into the clinical practice. The main advantages of warfarin are decades of treatment experience, the possibility to monitor its anticoagulant effect using the INR and the last, but not least, the low cost. Currently, approximately 75 % of anticoagulated patients in the Czech Republic are treated with warfarin and warfarin remains the only option for oral anticoagulant therapy in certain clinical conditions (particularly in patients with valvular atrial fibrillation or mechanical heart valves). For physicians across specialties it is still indispensable to master the basics of safe and effective warfarin therapy, including the management of treatment complications.Key words: anticoagulant therapy - INR - thrombosis - warfarin.
Subject(s)
Anticoagulants/therapeutic use , Warfarin/therapeutic use , Czech Republic , HumansABSTRACT
BACKGROUND: Adaptive response to hypoxia is regulated by several mechanisms and transcription factors, including hypoxia-inducible factors (HIFs). Activation of HIF-1α is associated with increased expression of P-glycoprotein and multidrug resistance in cancer cells. In this retrospective study, we analyzed candidate single-nucleotide polymorphisms (SNPs) in HIF-1α and HIF-1ß associated with risk of monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma (MM). PATIENTS AND METHODS: Genotypes of SNPs associated with hypoxia were determined in an independent cohort of monoclonal gammopathies (MG) (275 MM and 228 MGUS patients) and in 219 cancer-free controls by real time polymerase chain reaction allelic discrimination. RESULTS: When MM patients were compared to controls, protective role of CG genotype compared to CC in HIF-1ß (rs2228099) for MM development was observed (OR = 0.65; CI 0.45-0.95; p = 0.026). Even after adjustment for patients' age and body mass index (BMI), there were significantly lower odds (OR = 0.55; p = 0.045) of developing MM patients of CG genotype in comparison to CC genotype. Log-rank test confirmed association of GT haplotype (rs11549467, rs2057482) in HIF-1α with better overall survival (median 41.8 months; (CI 35.1-48.5)) for "none GT" and median 93.8 months (CI 31.3-156.4) for "at least one GT" haplotype (p = 0.0500). Further, significant associations between SNPs in MDR1 and outcome of MM were found in 110 MM patients that underwent bortezomib-based treatment. CONCLUSION: Our study showed a genetic predisposition for risk of MG development and/or outcome of MM patients; nevertheless, further studies are needed to confirm our initial analysis.
Subject(s)
Aryl Hydrocarbon Receptor Nuclear Translocator/genetics , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Paraproteinemias/genetics , ATP Binding Cassette Transporter, Subfamily B/genetics , Aged , Drug Resistance, Multiple/genetics , Female , Genetic Predisposition to Disease , Humans , Hypoxia/genetics , Male , Middle Aged , Multidrug Resistance-Associated Proteins/genetics , Polymorphism, Single Nucleotide , Progression-Free SurvivalABSTRACT
BACKGROUND: Aldehyde dehydrogenase (ALDH) is highly active in physiological stem cells as well as in tumor-initiating cells of some malignancies including multiple myeloma (MM). Finding higher activity of ALDH in some cell subsets in monoclonal gammopathies (MG) could identify potential source of myeloma-initiating cells (MICs). METHODS: Bone marrow of 12 MM, 9 monoclonal gammopathy of undetermined significance (MGUS), and 10 healthy donors (HD) were analyzed by flow cytometry. ALDH activity of B-cells and plasma cells (PC) was analyzed using Aldefluor. RESULTS: Similar changes of ALDH activity were found during B-cell development in HD and MG. Decreasing of ALDH activity from immature to naïve B-cells was found. In postgerminal stages, the activity started to increase, and in PCs, the ALDH activity was the same as in immature B-cells. Increased ALDH activity of all PC subsets compared to naïve B-cells was found in MM as well as in HD, while in MGUS, only CD19- PCs have higher ALDH activity. In HD, ALDH activity was higher in CD19+ PCs compared with MG. CONCLUSIONS: Our results indicate that changes of ALDH activity are the natural phenomenon in B-cell development; thus, high ALDH activity as a single marker is not appropriate for MICs identification.
Subject(s)
Aldehyde Dehydrogenase/metabolism , B-Lymphocytes/enzymology , Paraproteinemias/diagnosis , Paraproteinemias/enzymology , Plasma Cells/enzymology , Adult , Aged , Aged, 80 and over , Antigens, Surface/metabolism , B-Lymphocytes/pathology , Biomarkers , Bone Marrow/pathology , Case-Control Studies , Enzyme Activation , Female , Humans , Immunophenotyping , Male , Middle Aged , Monoclonal Gammopathy of Undetermined Significance/diagnosis , Monoclonal Gammopathy of Undetermined Significance/enzymology , Multiple Myeloma/diagnosis , Multiple Myeloma/enzymology , Neoplasm Staging , Plasma Cells/pathologyABSTRACT
OBJECTIVES: Long non-coding RNAs (lncRNAs) are RNA transcripts longer than 200 nucleotides that are not translated into proteins. They are involved in pathogenesis of many diseases including cancer and have a potential to serve as diagnostic and prognostic markers. We aimed to investigate lncRNA expression profiles in bone marrow plasma cells (BMPCs) of newly diagnosed multiple myeloma (MM) patients in comparison to normal BMPCs of healthy donors (HD) in a three-phase biomarker study. METHODS: Expression profile of 83 lncRNA was performed by RT2 lncRNA PCR Array (Qiagen), followed by quantitative real-time PCR using specific TaqMan non-coding RNA assays analyzing 84 newly diagnosed MM patients and 25 HD. RESULTS: Our analysis revealed dysregulation of two lncRNAs; NEAT1 (sensitivity of 55.0% and specificity of 79.0%) and UCA1 (sensitivity of 85.0% and specificity of 94.7%). UCA1 levels correlated with albumin and monoclonal immunoglobulin serum levels, cytogenetic aberrations, and survival of MM patients. CONCLUSION: Our study suggests a possible prognostic impact of UCA1 expression levels on MM patients.
Subject(s)
Biomarkers, Tumor , Gene Expression Regulation, Neoplastic , Multiple Myeloma/genetics , RNA, Long Noncoding/genetics , Aged , Aged, 80 and over , Biomarkers , Chromosome Aberrations , Diagnosis, Differential , Female , Gene Expression Profiling , Humans , In Situ Hybridization, Fluorescence , Kaplan-Meier Estimate , Male , Middle Aged , Multiple Myeloma/diagnosis , Multiple Myeloma/mortality , Multiple Myeloma/therapy , Neoplasm Staging , Prognosis , ROC Curve , Real-Time Polymerase Chain ReactionABSTRACT
Medication adherence is a complex problem reflecting variations in terms of medication taking behavior. It is essential in maximizing of the effect and risk minimization of the therapy and health care costs reduction, even in the case of oral anticoagulants (non-vitamin K antagonist oral anticoagulants - NOACs). The aim of this paper was to review the published literature and to discuss results in the field of medication adherence to NOACs in patients with non-valvular atrial fibrillation (NVAF). Based on the searching in databases Embase and PubMed 25 studies were identified, of which conclusions were summarized in this paper. Patients treated with dabigatran reported poorer medication adherence than patients with rivaroxaban. However, medication adherence is influenced by many circumstances as well as included studies were not sufficiently uniform, therefore, a prerequisite for further investigation of this issue is expected.Key words: apixaban - atrial fibrillation - dabigatran - medication adherence - patient compliance - rivaroxaban.