scholarly journals Prognostic Factors for Hospitalization of Children with Sickle Cell Anemia Treated with Hydroxyurea at Maximum Tolerated Dose

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2177-2177
Author(s):  
Jeremie H. Estepp ◽  
Qinlei T. Huang ◽  
Winfred C. Wang ◽  
Guolian Kang
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Area Under The Curve ◽  
Maximum Tolerated Dose ◽  
Composite Model ◽  
Operating Characteristics ◽  
Receiver Operating Characteristics Curve ◽  
Receiver Operating

Abstract Background: Hydroxyurea (HU) is recommended to be offered to children with sickle cell anemia (SCA; HbSS and HbSβ0 thalassemia) beginning at 9 months of age (Yawn, JAMA 2014). Intensifying HU to a maximum tolerated dose (MTD) provides fetal hemoglobin (HbF) levels of >20% (Ware, Blood 2010). Yet, children treated with HU at MTD still experience hospitalizations due to SCA-related complications (Nottage, PLoS One 2013). The ability to identify children at high risk of experiencing SCA-related complications while on HU would enhance clinical management and facilitate performance of clinical trials of novel agents. Our objective was to identify risk factors associated with hospitalization and to develop a prediction model for hospitalization of children treated with HU at MTD. Methods: The Hydroxyurea Study of Long-Term Effects (HUSTLE) is a prospective observational study (NCT00305175) designed to describe the clinical effects of HU in children with SCA. We have analyzed children who initiated HU per protocol and whose dose was escalated to MTD. Laboratory and clinical data were abstracted at baseline and at 9-12 months after enrollment. The first laboratory values of each interval were considered representative of the period. The primary outcome measure was hospitalization. After a multivariate regression logistic model identified risk factors for hospitalization based on a stepwise selection strategy, a smoothed receiver-operating-characteristic (ROC) curve was generated to predict hospitalization for the composite model and for each individual risk factor using the method of maximum-likelihood fitting of univariate distriubutions. Atlhough HbF was not identified in regression analysis among risk factors, because of its known effects as a disease modifier, it was inserted into the composite model. A prediction model was then generated for the identified risk factors utilizing optimal cutoff values defined by the maximum Youden method. Results: 151 children (mean [SD] age, 8.3 [5.0] years) were analyzed. HU resulted in higher HbF levels (22.6% [9.1] versus 10.1% [7.1]; p<0.0001), lower absolute neutrophil counts (4000/mm3 [2600] versus 7000/mm3 [3800]; p<0.0001), and fewer hospitalizations (7.8% [10/128] versus 28.9% [39/128]; p<0.0001) after 9-12 months compared to baseline. Children hospitalized after 9-12 months of therapy had similar HbF levels compared to those not hospitalized (OR 0.98 [95% CI: 0.9-1.1]; p=0.5), but higher total bilirubin (BiliT) (OR 1.3 [95% CI: 1.0-1.6]; p=0.03), blood urea nitrogen (BUN) (OR 1.3 [95% CI: 1.1-1.7]; p=0.19), and lactate dehydrogenase (LDH) (OR 1.01 [95% CI: 1.002-1.010]; p=0.006) levels. A ROC curve including insertion of HbF showed an area under the curve (AUC) of 0.90 (Figure 1). Optimal cutoffs for risk factors were: BiliT 1.05 mg/dL, BUN 8.5 mg/dL, and LDH 473 units/L. The probability of hospitalization varied in relation to identified risk factors (Table 1). Table 1. Predicted probability of hospitalization after 9-12 months of HU at MTD # of risk factors BiliT HbF BUN LDH Probability of ≥1.05(mg/dL) ≤20 (%) ≥8.5(mg/dL) ≥473(units/L) Hospitalization (%) 0 No No No No <1 1 Yes No No No <1 No Yes No No 1.3 No No Yes No 5.8 No No No Yes 19 2 Yes Yes No No <1 Yes No Yes No <1 Yes No No Yes 2.2 No Yes Yes No 10 No Yes No Yes 29 No No Yes Yes 65 3 Yes Yes Yes No 1.1 Yes Yes No Yes 3.8 Yes No Yes Yes 15 No Yes Yes Yes 77 4 Yes Yes Yes Yes 25 LDH, lactate dehydrogenase; BiliT, total bilirubin; BUN, blood urea nitrogen Discussion: In this pediatric cohort, HU therapy at MTD produced a robust laboratory response with most children having HbF >20% after 9-12 months. At such high levels of HbF, few children experienced a hospitalization due to its protective effects; however, we identified three laboratory parameters (LDH, BiliT, and BUN) that were predictive risk factors for children who continued to be hospitalized despite high levels of HbF. After 9-12 months of HU therapy at MTD the probability of hospitalization ranged from <1% to 65% for children with HbF of less than <20% and <1% to 77% in children with HbF of >20%. This model may help identify children at risk for complications of SCA while being treated with HU at MTD. Figure 1. Receiver-operating-characteristics curve for the risk of hospitalization as predicted by the composite model and for each identified risk factor. Area under the curve: composite model, 0.90; LDH, 0.74; BUN, 0.65; BiliT, 0.59; HbF, 0.53 Figure 1. Receiver-operating-characteristics curve for the risk of hospitalization as predicted by the composite model and for each identified risk factor. Area under the curve: composite model, 0.90; LDH, 0.74; BUN, 0.65; BiliT, 0.59; HbF, 0.53 Disclosures Estepp: Eli Lilly and Company: Research Funding; Daiichi Sankyo: Research Funding. Off Label Use: Off label use of hydroxyurea in children with sickle cell anemia.

scholarly journals Prevalence of Pulmonary Hypertension in Sickle Cell Anemiai Patient in KSA

2021 ◽  
pp. 214-220
Author(s):  
Eman AbdulAziz Balbaid ◽  
Manal abdulaziz Murad ◽  
Hoda Jehad Abousada ◽  
Abdurrahman Yousuf Banjar ◽  
Mashael Abdulghani Taj ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Nervous System ◽  
Saudi Arabia ◽  
Risk Factor ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Cardiac Disease ◽  
Kingdom Of Saudi Arabia ◽  
Cross Sectional ◽  
Increased Risk

Introduction: Pulmonary hypertension (PH) is a relatively common and severe complication of SCI and an independent risk factor for mortality. Sickle cell disease is considered one of the most common diseases in the Kingdom of Saudi Arabia. When a healthy disease related to cardiovascular health is highlighted, sickle cell anemia may be the most common and related disease in high pulmonary pressure. In this study, we aimed to determine prevalence of PHTN in SCA patient, and associated risk factors with it.   Methodology: This is an analytical cross-sectional study conducted in kingdom of Saudi Arabia (General population, SCA patient and CVD patient), from 29/7/2020 till 15/11/2020. The study was depending on online self-reported questionnaire that included assessing the demographic factors as gender, nationality besides, disease-related information:  SCA patient , CVD patient and DM patient. Results: we received 794 responses to our questionnaire where 93.5% of them were Saudi Arabian.  The prevalence of sickle cell anemia is 8.8%. Male represented 29.8% of patients while female represented 52.2% of patients. In SCA patients, the prevalence of PHTN was 31.8%. Moreover, it was found that having cardiac disease is considered a risk factor for developing PHTN where 37.7% of patients having cardiac disease had PHTN compared with 6.2% of health patients (OD: 9.16, 95% CI: 5.5479 to 15.13, P=0.000) while diabetes mellitus increase risk for developing PHTN by more than seven fold (OD: 7.6, 95% CI; 4.7175 to 12.4, P=0.000) and disorder of nervous system by 12 folds (OD: 12.7; 95% CI: 7.6658 to 21.09, P=0.000). Conclusion: we had found that the prevalence if SCA among Saudi Arabia is 8.8% with a higher prevalence in female than male. Moreover, the prevalence of PHTN in SCA patients was high about 31.8% which is much higher than its prevalence in normal individuals. Moreover, it was found that having cardiac disease is considered a risk factor for developing PHTN besides, having diabetic condition and disorder of nervous system which increased risk for developing PHTN in SCA by nine, seven and 12-fold respectively.

scholarly journals HMOX1 and Acute Kidney Injury in Sickle Cell Anemia

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 686-686
Author(s):  
Santosh L. Saraf ◽  
Maya Viner ◽  
Ariel Rischall ◽  
Binal Shah ◽  
Xu Zhang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Risk Factor ◽  
Kidney Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Kidney Injury ◽  
Ckd Progression ◽  
Kdigo Guidelines

Abstract Acute kidney injury (AKI) is associated with tubulointerstitial fibrosis and nephron loss and may lead to an increased risk for subsequently developing chronic kidney disease (CKD). In adults with sickle cell anemia (SCA), high rates of CKD have been consistently observed, although the incidence and risk factors for AKI are less clear. We evaluated the incidence of AKI, defined according to Kidney Disease Improving Global Outcomes (KDIGO) guidelines as a rise in serum creatinine by ≥0.3mg/dL within 48 hours or ≥1.5 times baseline within seven days, in 158 of 299 adult SCA patients enrolled in a longitudinal cohort from the University of Illinois at Chicago. These patients were selected based on the availability of genotyping for α-thalassemia, BCL11A rs1427407, APOL1 G1/G2, and the HMOX1 rs743811 and GT-repeat variants. Median values and interquartile range (IQR) are provided. With a median follow up time of 66 months (IQR, 51-74 months), 137 AKI events were observed in 63 (40%) SCA patients. AKI was most commonly observed in the following settings: acute chest syndrome (25%), an uncomplicated vaso-occlusive crisis (VOC)(24%), a VOC with pre-renal azotemia determined by a fractional excretion of sodium &lt;1% or BUN-to-creatinine ratio &gt;20:1 (14%), or a VOC with increased hemolysis, defined as an increase in serum LDH or indirect bilirubin level &gt;1.5 times over the baseline value at the time of enrollment (12%). Compared to individuals who did not develop AKI, SCA adults who developed an AKI event were older (AKI: median and IQR age of 35 (26-46) years, no AKI: 28 (23 - 26) years; P=0.01) and had a lower estimated glomerular filtration rate (eGFR) (AKI: median and IQR eGFR of 123 (88-150) mL/min/1.73m2, no AKI: 141 (118-154) mL/min/1.73m2; P=0.02) by the Kruskal-Wallis test at the time of enrollment. We evaluated the association of a panel of candidate gene variants with the risk of developing an AKI event. These included loci related to the degree of hemolysis (α-thalassemia, BCL11A rs1427407), to chronic kidney disease (APOL1 G1/G2 risk variants), and to heme metabolism (HMOX1) . Using a logistic regression model that adjusted for age and eGFR at the time of enrollment, the risk of an AKI event was associated with older age (10-year OR 2.6, 95%CI 1.4-4.8, P=0.002), HMOX1 rs743811 (OR 3.1, 95%CI 1.1-8.7, P=0.03), and long HMOX1 GT-repeats, defined as &gt;25 repeats (OR 2.5, 95%CI 1.01-6.1, P=0.04). Next, we assessed whether AKI is associated with a more rapid decline in eGFR and with CKD progression, defined as a 50% reduction in eGFR, on longitudinal follow up. Using a mixed effects model that adjusted for age and eGFR at the time of enrollment, the rate of eGFR decline was significantly greater in those with an AKI event (β = -0.51) vs. no AKI event (β = -0.16) (P=0.03). With a median follow up time of 66 months (IQR, 51-74 months), CKD progression was observed in 21% (13/61) of SCA patients with an AKI event versus 9% (8/88) without an AKI event. After adjusting for age and eGFR at the time of enrollment, the severity of an AKI event according to KDIGO guidelines (stage 1 if serum creatinine rises 1.5-1.9 times baseline, stage 2 if the rise is 2.0-2.9 times baseline, and stage 3 if the rise is ≥3 times baseline or ≥4.0 mg/dL or requires renal replacement therapy) was a risk factor for CKD progression (unadjusted HR 1.6, 95%CI 1.1-2.3, P=0.02; age- and eGFR-adjusted HR 1.6, 95%CI 1.1-2.5, P=0.03). In conclusion, AKI is commonly observed in adults with sickle cell anemia and is associated with increasing age and the HMOX1 GT-repeat and rs743811 polymorphisms. Furthermore, AKI may be associated with a steeper decline in kidney function and more severe AKI events may be a risk factor for subsequent CKD progression in SCA. Future studies understanding the mechanisms, consequences of AKI on long-term kidney function, and therapies to prevent AKI in SCA are warranted. Disclosures Gordeuk: Emmaus Life Sciences: Consultancy.

scholarly journals Silent infarct is a risk factor for infarct recurrence in adults with sickle cell anemia

Neurology ◽  
2018 ◽  
Vol 91 (8) ◽  
pp. e781-e784 ◽  
Author(s):  
Lori C. Jordan ◽  
Adetola A. Kassim ◽  
Manus J. Donahue ◽  
Meher R. Juttukonda ◽  
Sumit Pruthi ◽  
...  
Keyword(s):  
Risk Factor ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Cox Regression ◽  
Brain Mri ◽  
Treatment Strategies ◽  
Significant Risk ◽  
Rank Test ◽  
Event Analysis ◽  
Log Rank Test

ObjectiveBecause of the high prevalence of silent cerebral infarcts (SCIs) in adults with sickle cell anemia (SCA) and lack of information to guide treatment strategies, we evaluated the risk of recurrent SCIs and overt stroke in adults with SCA with preexisting SCI.MethodsThis observational study included adults with SCA (HbSS or Sβ0 thalassemia) aged 18 to 40 years. Participants received 3-tesla brain MRI and a detailed neurologic examination. Time-to-event analysis assessed those with or without baseline SCI and with new or progressive infarcts. The incidence rate of new events was compared by log-rank test. Univariable Cox regression assessed the association of SCI with infarct progression.ResultsAmong adults with SCA with 2 MRIs and at least 6 months between MRIs (n = 54, mean interval = 2.5 years), 43% had SCI at baseline. Of participants with baseline SCI, 30% had new or progressive SCI over 2.5 years compared to 6% with no SCI at baseline; no participant had an overt stroke. New SCIs at follow-up were present in 12.9 per 100 patient-years with existing SCI compared with 2.4 per 100 patient-years without prior SCI (log-rank test, p = 0.021). No statistically significant differences were seen among those with or without baseline SCI in use of hydroxyurea therapy, hydroxyurea dose, or other stroke risk factors. The presence of SCI was associated with increased hazard of a new or progressive infarct (hazard ratio 5.27, 95% confidence interval 1.09–25.51, p = 0.039).ConclusionsSilent infarcts in adults with SCA are common and are a significant risk factor for future silent infarcts.

Sensitivity and specificity of Sirius indices in diagnosis of keratoconus and suspect keratoconus

2021 ◽  
pp. 112067212110601
Author(s):  
Abdelrahman Salman ◽  
Taym Darwish ◽  
Ali Ali ◽  
Marwan Ghabra ◽  
Rafea Shaaban
Keyword(s):  
Sensitivity And Specificity ◽  
Predictive Accuracy ◽  
Corneal Thickness ◽  
Case Series ◽  
Area Under The Curve ◽  
Receiver Operating Characteristics ◽  
Operating Characteristics ◽  
Symmetry Index ◽  
Case Series Study ◽  
Receiver Operating

Aim To estimate the sensitivity and specificity of topographic and tomographic corneal parameters as determined by Sirius (CSO, Florence, Italy) in discriminating keratoconus (KC) and suspect keratoconus from normal cornea. Method In this retrospective case-series study, keratoconus screening indices were measured using Sirius tomographer. Receiver operating characteristics (ROC) curves were used to determine the test's overall predictive accuracy (area under the curve) and to identify optimal cut-off points to maximize sensitivity and specificity in differentiating keratoconus and suspect keratoconus from normal corneas. Results Receiver operating characteristics (ROC) curve analyses showed high predictive accuracy for Symmetry Index back (SIb), Keratoconus Vertex front (KVf), Symmetry Index front (SIf), Keratoconus Vertex back (KVb), Apex Keratometry (Curve-Apex) and Minimum corneal Thickness (ThkMin) to distinguish keratoconus from normal (area under the curve > 0.9, all). Symmetry Index back was identified as the best diagnostic parameter for detecting suspect keratoconus with AUC of 0.86. Highest specificity to detect keratoconus and suspect keratoconus was seen for SIb, 99.87% and 84.66%, respectively. These values were associated with optimal cut-off points of 0.46 D for keratoconus and 0.12 D for suspect keratoconus. Conclusion Sirius parameters evaluated in the study were effective to differentiate keratoconus from normal corneas. However, Symmetry Index back was the index with the highest ability to detect suspect keratoconus.

scholarly journals qTICI: Quantitative assessment of brain tissue reperfusion on digital subtraction angiograms of acute ischemic stroke patients

2020 ◽  
pp. 174749302090963
Author(s):  
Haryadi Prasetya ◽  
Lucas A Ramos ◽  
Thabiso Epema ◽  
Kilian M Treurniet ◽  
Bart J Emmer ◽  
...  
Keyword(s):  
Functional Outcome ◽  
Digital Subtraction Angiography ◽  
Quantitative Measure ◽  
Receiver Operating Characteristics ◽  
Binary Logistic Regression Analysis ◽  
Digital Subtraction ◽  
Operating Characteristics ◽  
Vessel Occlusion ◽  
Receiver Operating Characteristics Curve ◽  
Receiver Operating

Background The Thrombolysis in Cerebral Infarction (TICI) scale is an important outcome measure to evaluate the quality of endovascular stroke therapy. The TICI scale is ordinal and observer-dependent, which may result in suboptimal prediction of patient outcome and inconsistent reperfusion grading. Aims We present a semi-automated quantitative reperfusion measure (quantified TICI (qTICI)) using image processing techniques based on the TICI methodology. Methods We included patients with an intracranial proximal large vessel occlusion with complete, good quality runs of anteroposterior and lateral digital subtraction angiography from the MR CLEAN Registry. For each vessel occlusion, we identified the target downstream territory and automatically segmented the reperfused area in the target downstream territory on final digital subtraction angiography. qTICI was defined as the percentage of reperfused area in target downstream territory. The value of qTICI and extended TICI (eTICI) in predicting favorable functional outcome (modified Rankin Scale 0–2) was compared using area under receiver operating characteristics curve and binary logistic regression analysis unadjusted and adjusted for known prognostic factors. Results In total, 408 patients with M1 or internal carotid artery occlusion were included. The median qTICI was 78 (interquartile range 58–88) and 215 patients (53%) had an eTICI of 2C or higher. qTICI was comparable to eTICI in predicting favorable outcome with area under receiver operating characteristics curve of 0.63 vs. 0.62 (P = 0.8) and 0.87 vs. 0.86 (P = 0.87), for the unadjusted and adjusted analysis, respectively. In the adjusted regression analyses, both qTICI and eTICI were independently associated with functional outcome. Conclusion qTICI provides a quantitative measure of reperfusion with similar prognostic value for functional outcome to eTICI score.

scholarly journals Optimizing hydroxyurea therapy for sickle cell anemia

Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 436-443 ◽  
Author(s):  
Russell E. Ware
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Fetal Hemoglobin ◽  
Maximum Tolerated Dose ◽  
Sub Saharan Africa ◽  
Future Research ◽  
Published Evidence ◽  
Treatment Indications ◽  
Hydroxyurea Treatment ◽  
Hydroxyurea Therapy

Abstract Hydroxyurea has proven efficacy in numerous clinical trials as a disease-modifying treatment for patients with sickle cell anemia (SCA) but is currently under-used in clinical practice. To improve the effectiveness of hydroxyurea therapy, efforts should be directed toward broadening the clinical treatment indications, optimizing the daily dosage, and emphasizing the benefits of early and extended treatment. Here, various issues related to hydroxyurea treatment are discussed, focusing on both published evidence and clinical experience. Specific guidance is provided regarding important but potentially unfamiliar aspects of hydroxyurea treatment for SCA, such as escalating to maximum tolerated dose, treating in the setting of cerebrovascular disease, switching from chronic transfusions to hydroxyurea, and using serial phlebotomy to alleviate iron overload. Future research directions to optimize hydroxyurea therapy are also discussed, including personalized dosing based on pharmacokinetic modeling, prediction of fetal hemoglobin responses based on pharmacogenomics, and the risks and benefits of hydroxyurea for non-SCA genotypes and during pregnancy/lactation. Another critical initiative is the introduction of hydroxyurea safely and effectively into global regions that have a high disease burden of SCA but limited resources, such as sub-Saharan Africa, the Caribbean, and India. Final considerations emphasize the long-term goal of optimizing hydroxyurea therapy, which is to help treatment become accepted as standard of care for all patients with SCA.

scholarly journals Evaluating risk factors for chronic kidney disease in pediatric patients with sickle cell anemia

2017 ◽  
Vol 32 (9) ◽  
pp. 1565-1573 ◽  
Author(s):  
Jeffrey D. Lebensburger ◽  
Gary R. Cutter ◽  
Thomas H. Howard ◽  
Paul Muntner ◽  
Daniel I. Feig
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Pediatric Patients

scholarly journals Preoperative retrolisthesis as a risk factor of postdecompression lumbar disc herniation

2016 ◽  
Vol 24 (4) ◽  
pp. 592-601 ◽  
Author(s):  
Shota Takenaka ◽  
Kosuke Tateishi ◽  
Noboru Hosono ◽  
Yoshihiro Mukai ◽  
Takeshi Fuji
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Spinal Stenosis ◽  
Lumbar Spinal Stenosis ◽  
Lumbar Disc Herniation ◽  
Disc Herniation ◽  
Lumbar Disc ◽  
Area Under The Curve ◽  
Lumbar Spinal ◽  
Acute Sciatica

OBJECT In this study, the authors aimed to identify specific risk factors for postdecompression lumbar disc herniation (PDLDH) in patients who have not undergone discectomy and/or fusion. METHODS Between 2007 and 2012, 493 patients with lumbar spinal stenosis underwent bilateral partial laminectomy without discectomy and/or fusion in a single hospital. Eighteen patients (herniation group [H group]: 15 men, 3 women; mean age 65.1 years) developed acute sciatica as a result of PDLDH within 2 years after surgery. Ninety patients who did not develop postoperative acute sciatica were selected as a control group (C group: 75 men, 15 women; mean age 65.4 years). Patients in the C group were age and sex matched with those in the H group. The patients in the groups were also matched for decompression level, number of decompression levels, and surgery date. The radiographic variables measured included percentage of slippage, intervertebral angle, range of motion, lumbar lordosis, disc height, facet angle, extent of facet removal, facet degeneration, disc degeneration, and vertebral endplate degeneration. The threshold for PDLDH risk factors was evaluated using a continuous numerical variable and receiver operating characteristic curve analysis. The area under the curve was used to determine the diagnostic performance, and values greater than 0.75 were considered to represent good performance. RESULTS Multivariate analysis revealed that preoperative retrolisthesis during extension was the sole significant independent risk factor for PDLDH. The area under the curve for preoperative retrolisthesis during extension was 0.849; the cutoff value was estimated to be a retrolisthesis of 7.2% during extension. CONCLUSIONS The authors observed that bilateral partial laminectomy, performed along with the removal of the posterior support ligament, may not be suitable for lumbar spinal stenosis patients with preoperative retrolisthesis greater than 7.2% during extension.

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