Improvement in hemolysis and pulmonary arterial systolic pressure in adult patients with sickle cell disease during treatment with hydroxyurea.
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ABSTRACT:
SUBMITTER: Olnes M
PROVIDER: S-EPMC2766189 | biostudies-literature | 2009 Aug
REPOSITORIES: biostudies-literature
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Improvement in hemolysis and pulmonary arterial systolic pressure in adult patients with sickle cell disease during treatment with hydroxyurea.
Olnes Matthew M Chi Amy A Haney Carissa C May Rose R Minniti Caterina C Taylor James J Kato Gregory J GJ
American journal of hematology 20090801 8
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Project description:Background: Despite a high incidence of sickle cell anemia, hydroxyurea (HU) treatment is rarely used in the DR Congo. This study aims to assess the efficacy of HU, the incidence of side effects that may limit its use in adults and to determine the dose needed for clinical improvement in patients. Methods: In a prospective study, patients received an initial dose of 15 mg/kg/day which was increased by 5 mg/kg every 6 months, up to a maximum of 30 mg/kg/day. The response and side effects to HU were evaluated biologically and clinically every 3 months during a 2-year period. Results: Seventy adult patients with a moderate or severe clinical phenotype initiated treatment. Only minor side effects were reported. At the end of the 2-year treatment phase, 45 (64.3%) had dropped out, of whom 33 were without a clear reason. Clinical and biological improvement was more marked during the first year. There was a reduction in severe vaso-occlusive crises (p < 0.001), need for transfusion (p < 0.001), and hospitalization days (p = 0.038). Fetal hemoglobin (HbF) levels increased on average 2.9 times after 12 months (p < 0.001). The increase in mean corpuscular volume was greater in the first year (p < 0.001) than in the second year (p = 0.041). The decrease in leukocytes (p < 0.001) was significant during the first year. In 70% of patients, the 20 mg/kg/day dose was needed to reach the 20% HbF threshold. Conclusion: HU is effective and well tolerated. The magnitude of the response varies from one patient to another. Improvement of clinical manifestations is achieved in most patients with a relatively low dose. Effective implementation of HU treatment will require improved adherence to treatment.
| S-EPMC10435708 | biostudies-literature
Project description:BackgroundTo explore the association between the ratio of tricuspid annular plane systolic excursion (TAPSE) and pulmonary arterial systolic pressure (PASP), and long- and short-term outcomes in mechanically ventilated septic shock patients.MethodsSeptic shock patients admitted to the intensive care unit (ICU) were screened for enrollment. Echocardiographic parameters including TAPSE and tricuspid regurgitation velocity, haemodynamic and respiratory parameters, and prognostic data were obtained.ResultsOne hundred eighteen subjects were enrolled in this study, among whom 75 survived and 43 died at the one-year follow-up. ROC curve analysis revealed that the TAPSE/PASP ratio was able to assess one-year all-cause mortality with an area under the curve of 0.817 (95% CI: 0.739-0.896, p < 0.001) and the optimal cutoff value was 0.50 mm/mmHg. Kaplan-Meier survival analysis showed that one-year all-cause mortality was significantly higher in patients with TAPSE/PASP ≤0.5 mm/mmHg than in patients with TAPSE/PASP > 0.5 mm/mmHg (log-rank 32.934, p < 0.001). According to the Cox regression survival analyses, the TAPSE/PASP ratio was independently associated with one-year all-cause mortality (HR 0.007, 95% CI:0.000-0.162, p = 0.002) and ICU mortality (HR 0.027, 95% CI:0.001-0.530, p = 0.017). According to the multivariable analysis, the TAPSE/PASP ratio was an independent variable associated with mechanical ventilation (MV) duration (standard coefficient - 0.240, p = 0.010).ConclusionThe TAPSE/PASP ratio demonstrated prognostic value for one-year all-cause mortality, ICU mortality and MV duration in mechanically ventilated septic shock patients.
| S-EPMC7293130 | biostudies-literature
Project description:BackgroundThe ratios of tricuspid annular plane systolic excursion (TAPSE)/echocardiographically measured systolic pulmonary artery pressure (PASP), fractional area change/invasively measured mean pulmonary artery pressure, right ventricular (RV) area change/end-systolic area, TAPSE/pulmonary artery acceleration time, and stroke volume/end-systolic area have been proposed as surrogates of RV-arterial coupling. The relationship of these surrogates with the gold standard measure of RV-arterial coupling (invasive pressure-volume loop-derived end-systolic/arterial elastance [Ees/Ea] ratio) and RV diastolic stiffness (end-diastolic elastance) in pulmonary hypertension remains incompletely understood. We evaluated the relationship of these surrogates with invasive pressure-volume loop-derived Ees/Ea and end-diastolic elastance in pulmonary hypertension.MethodsWe performed right heart echocardiography and cardiac magnetic resonance imaging 1 day before invasive measurement of pulmonary hemodynamics and single-beat RV pressure-volume loops in 52 patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. The relationships of the proposed surrogates with Ees/Ea and end-diastolic elastance were evaluated by Spearman correlation, multivariate logistic regression, and receiver operating characteristic analyses. Associations with prognosis were evaluated by Kaplan-Meier analysis.ResultsTAPSE/PASP, fractional area change/mean pulmonary artery pressure, RV area change/end-systolic area, and stroke volume/end-systolic area but not TAPSE/pulmonary artery acceleration time were correlated with Ees/Ea and end-diastolic elastance. Of the surrogates, only TAPSE/PASP emerged as an independent predictor of Ees/Ea (multivariate odds ratio: 18.6; 95% CI, 0.8-96.1; P=0.08). In receiver operating characteristic analysis, a TAPSE/PASP cutoff of 0.31 mm/mm Hg (sensitivity: 87.5% and specificity: 75.9%) discriminated RV-arterial uncoupling (Ees/Ea <0.805). Patients with TAPSE/PASP <0.31 mm/mm Hg had a significantly worse prognosis than those with higher TAPSE/PASP.ConclusionsEchocardiographically determined TAPSE/PASP is a straightforward noninvasive measure of RV-arterial coupling and is affected by RV diastolic stiffness in severe pulmonary hypertension.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT03403868.
| S-EPMC7099862 | biostudies-literature
Project description:ObjectiveTo determine whether different changes of pulmonary artery systolic pressure (PASP) after surgeries have an impact on the long-term outcomes in patients with rheumatic and degenerative mitral valve (MV) disease and atrial fibrillation.MethodsBetween 2004 and 2016, 1,188 patients with rheumatic and degenerative MV disease undergoing MV and Cox-Maze procedure were identified. Clinic outcomes, as well as rhythm state and echocardiography indices in long-term follow-up were recorded. Patients were grouped by the changes of PASP (persistently normal, persistently increased, increased, and decreased) from preoperative estimation to follow-up.ResultsA complete echocardiography was performed at baseline and after 5 years. During follow-up, free of death and atrial fibrillation (AF) off antiarrhythmic drugs was 90 and 61%, 78 and 41% at 5 and 10 years, respectively. Survival rate was higher in patients with persistently normal and became worse in patients with persistently increased and increased PASP (log-rank 166.0, P < 0.0001). Moreover, the patients with persistently normal PASP had a lowest risk of recurrent AF (SHR: 0817; CI: 0.765-0.872; P < 0.0001) after considering death as a competing risk. A persistently normal PASP at follow-up and degenerative MV disease were associated with improved survival and sinus rhythm (SR) maintenance at multivariable Cox regression analysis (P < 0.05).ConclusionPatients with degenerative MV disease or have persistently normal PASP during follow-up have better survival and SR maintenance rate than patients with either rheumatic MV disease or persistently abnormal PASP.
| S-EPMC9868267 | biostudies-literature
Project description:Profound hypotension during liver transplantation is aggressively treated with vasopressors thus frequently unrevealed in a retrospective study. The relationship between concealed intraoperative hypotension and in-hospital mortality after liver transplantation was evaluated using performance measurement (PM) of systolic arterial pressure (SAP). Median performance error (MDPE), median absolute performance error (MDAPE), and wobble of SAP were calculated using preoperative SAP as the reference value, and prereperfusion and postreperfusion SAPs as measured values. Univariable and multivariable logistic regression analyses were performed using 6 PM parameters and 36 traditional SAP-derived parameters to predict in-hospital mortality. In-hospital mortality was 3.9% (22/569 cases). Prereperfusion MDAPE and postreperfusion wobble were the only significant SAP-derived predictors of in-hospital mortality. The area under receiver operating characteristic curve of prediction model was 0.769 (95% confidence interval 0.732-0.803, P < 0.001; sensitivity = 55%, specificity = 94%). Severe hypotension during liver transplantation is concealed by proactive vasopressor treatment thus traditional measures of hypotension generally fail to detect the masked hypotension in retrospective analysis. PM analysis of intraoperative SAP including prereperfusion MDAPE and postreperfusion wobble is most likely to detect treated and therefore concealed hypotension, and was able to independently and quantitatively predict in-hospital mortality after liver transplantation with high diagnostic specificity.
| S-EPMC5539171 | biostudies-literature
Project description:A 22-year-old male presented with recurrent stroke, central cyanosis, and dyspnea. Transesophageal echocardiography and cardiac catheterization revealed bidirectional shunt flow through atrial septal defect (ASD) without pulmonary arterial hypertension. The orifice of inferior vena cava facing towards ASD opening led partially right to left shunt resulting in cyanosis with normal pulmonary arterial pressure.
| S-EPMC4286645 | biostudies-literature
Project description:BackgroundWe investigated the feasibility of the clinical application of non-invasive transthoracic echocardiography for diagnosis of pulmonary arterial hypertension induced by dasatinib (D-PAH) in chronic myeloid leukemia (CML).MethodsA total of 451 CML patients who were examined by 2D-echocardiography at least once at baseline and/or during dasatinib therapy as frontline (n = 196) and subsequent line (n = 255) therapies were included in this study. D-PAH was defined as right ventricular systolic pressure (RVSP) >40 mm Hg with relevant symptoms and the absence of other specific etiologies.ResultsA total of 847 echocardiographies were performed including at baseline (n = 255) and during dasatinib treatment (n = 592). During the median of 36.2 (0.1-181.8) months of dasatinib therapy, the level of RVSP gradually increased (Spearman's r = 0.2819, p < 0.001) and the mean RVSP was significantly increased after taking dasatinib therapy compared with baseline. During dasatinib therapy, 56 (12.4%) patients had RVSP >40 mm Hg without (asymptomatic, n = 27, 48.2%) or with symptoms (D-PAH, n = 29, 51.8%). All asymptomatic patients maintained dasatinib therapy without further symptoms and the D-PAH patients ultimately switched to other tyrosine kinase inhibitors. After dasatinib discontinuation, 13 (45%) and 15 (52%) patients showed RVSP normalization and gradual decrease, respectively.ConclusionsOur large cohort study demonstrated that the gradual increment of RVSP might be induced by dasatinib and non-invasive echocardiography can be fast way for early diagnosis as well as for monitoring of D-PAH.
| S-EPMC7940235 | biostudies-literature
Project description:ObjectiveThe aim of this study was to assess the prognostic value of systolic pulmonary artery pressure (sPAP) estimated by echocardiography in the multinational European League Against Rheumatism Scleroderma Trial and Research (EUSTAR) cohort.MethodsData for patients with echocardiography documented between 1 January 2005 and 31 December 2011 were extracted from the EUSTAR database. Stepwise forward multivariable statistical Cox pulmonary hypertension analysis was used to examine the independent effect on survival of selected variables.ResultsBased on our selection criteria, 1476 patients were included in the analysis; 87% of patients were female, with a mean age of 56.3 years (s.d. 13.5) and 31% had diffuse SSc. The mean duration of follow-up was 2.0 years (s.d. 1.2, median 1.9). Taking index sPAP of <30 mmHg as reference, the hazard ratio (HR) for death was 1.67 (95% CI 0.92, 2.96) if the index sPAP was between 30 and 36 mmHg, 2.37 (95% CI 1.14, 4.93) for sPAP between 36 and 40 mmHg, 3.72 (95% CI 1.61, 8.60) for sPAP between 40 and 50 mmHg and 9.75 (95% CI 4.98, 19.09) if sPAP was >50 mmHg. In a multivariable Cox model, sPAP and the diffusing capacity for carbon monoxide (DLCO) were independently associated with the risk of death [HR 1.833 (95% CI 1.035, 3.247) and HR 0.973 (95% CI 0.955, 0.991), respectively]. sPAP was an independent risk factor for death with a HR of 3.02 (95% CI 1.91, 4.78) for sPAP ≥36 mmHg.ConclusionAn estimated sPAP >36 mmHg at baseline echocardiography was significantly and independently associated with reduced survival, regardless of the presence of pulmonary hypertension based on right heart catheterization.
| S-EPMC4473765 | biostudies-literature
Project description:BACKGROUND:Hydroxyurea (HU) is a FDA- and EMA-approved drug that earned an important place in the treatment of patients with severe sickle cell anemia (SCA) by showing its efficacy in many studies. This medication is still underused due to fears of physicians and families and must be optimized. METHODS:We analyzed our population and identified HU pharmacokinetic (PK) parameters in order to adapt treatment in the future. Working with a pediatric population, we searched for the most indicative sampling time to reduce the number of samples needed. RESULTS:Nine children treated by HU for severe SCA were included for this PK study. HU quantification was made using a validated gas chromatography/mass spectrometry (GC/MS) method. Biological parameters (of effectiveness and compliance) and clinical data were collected. None of the nine children reached the therapeutic target defined by Dong et al. as an area under the curve (AUC) = 115 h.mg/L; four patients were suspected to be non-compliant. Only two patients had an HbF over 20%. The 2 h sample was predictive of the medication exposure (r2 = 0.887). CONCLUSIONS:It is urgent to be more efficient in the treatment of SCA, and pharmacokinetics can be an important asset in SCA patients.
| S-EPMC6833033 | biostudies-literature
Project description:Hydroxyurea (HU) has been used clinically to reduce the frequency of painful crisis and the need for blood transfusion in sickle cell disease (SCD) patients. However, the mechanisms underlying such beneficial effects of HU treatment are still not fully understood. Studies have indicated a weak correlation between clinical outcome and molecular markers, and the scientific quest to develop companion biophysical markers have mostly targeted studies of blood properties under hypoxia. Using a common-path interferometric technique, we measure biomechanical and morphological properties of individual red blood cells in SCD patients as a function of cell density, and investigate the correlation of these biophysical properties with drug intake as well as other clinically measured parameters. Our results show that patient-specific HU effects on the cellular biophysical properties are detectable at normoxia, and that these properties are strongly correlated with the clinically measured mean cellular volume rather than fetal hemoglobin level.
| S-EPMC5003247 | biostudies-literature