scholarly journals Impact of Oral Arginine Therapy on Global Arginine Bioavailability in Nigerian Children with Sickle Cell Anemia and Vaso-Occlusive Pain

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 22-23
Author(s):  
Richard Onalo ◽  
Peter Cooper ◽  
Barend C. Vorster ◽  
Marli Dercksen ◽  
Antoinette Cilliers ◽  
...  
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Opioid Use ◽  
Nigerian Children ◽  
Pain Scores ◽  
The Us ◽  
Plasma Arginine ◽  
The Impact ◽  
Arginine Concentration ◽  
Arginine Supplementation

Introduction: Severe vaso-occlusive pain episodes (VOE) are a major cause of morbidityand mortality in sickle cell anemia (SCA). Low arginine bioavailability is associated with pain severity and predicts need for pediatric hospitalization (Morris et. al, 2000). Arginine supplementation has opioid-sparing effects and was found to significantly decrease pain scores in children hospitalized with SCA-VOE compared to placebo in phase-2 randomized placebo-controlled trials (RCT) performed in the United States (US, Morris et. al, 2013) and Nigeria (Onalo et al, ASH 2019), while also significantly decreased time-to-crisis-resolution and length of hospital stay (LOS) in Nigerian children (Onalo et al, ASH 2019). Its mechanism-of-action and impact on arginine bioavailability is unclear. Objectives: To determine the impact of oral arginine supplementation on arginine bioavailability and total opioid use in children with SCA-VOE. Methods: A double-blind RCT of oral L-arginine (100 mg/kg/dose every 8 hours until discharge; up to 15 doses maximum) was performed in children with SCA hospitalized with severe VOE defined as a Numerical Pain Scale Score (PS) of at least 7 on a scale of 0-10, at one of two hospitals in Abuja, Nigeria (clinical outcomes previously reported, Onalo et al ASH 2019). Plasma arginine concentration and the global arginine bioavailability ratio (GABR, defined as arginine/[ornithine+citrulline]) was measured with high performance liquid chromatography tandem mass spectrometry before supplementation and at day 5 or discharge, whichever came first. Indices of arginine bioavailability were calculated and compared between the study groups. Demographics, clinical characteristics and total opioid use (mg/kg of morphine equivalents) were obtained. The impact of oral arginine supplementation on arginine bioavailability, and correlation of changes in arginine bioavailability with total opioid use was assessed. Results: Sixty-eight children with SCA were recruited, aged 5-17years (mean: 10.6±0.4 years), and 85% were male; 35 children were randomized into the arginine arm and 33 into the placebo arm. Baseline characteristics were similar between arms. Clinical outcomes of significantly lower total analgesic use, lower pain scores, decreased time-to-crisis resolution and shorter LOS in the arginine group vs. placebo were previously reported (Onalo et al, ASH 2019). Oral arginine supplementation increases plasma arginine levels by 125% [95% CI, 61-187%] in the arginine as against 29% [1-58%] in the placebo group (Table 1), p=0.007. GABR was higher after supplementation in patients treated with arginine: 59% [20-98%] vs. -2% [-27-22%] in the placebo group (p=0.009). Patients with the lowest arginine level at presentation experienced the greatest increase in plasma arginine concentration, particularly patients with acute chest syndrome (ACS). Percent increase in GABR inversely correlated with total opioid used (mg/kg; r=-0.35;p=0.02, figure 1). Conclusion: Arginine deficiency plays a role in acute pain requiring hospitalization in Nigerian children with SCA, similar to what has been reported in the US. Plasma arginine levels significantly increased with arginine supplementation, and improved global arginine bioavailability was inversely associated with total opioids used in VOE management. Lowest arginine levels were found in children with ACS, as previously reported in the US (Morris et al, 2000), a phenomenon that warrants further investigation. Low arginine bioavailability in children with SCA-VOE is improved by oral arginine supplementation. Funded by Tertiary Education Trust Fund (to RO) and in part by NIH/NCCIH K24AT009893 (to CRM); Pan African Clinical Trial Registry number PACTR 201611001864290). Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: Oral L-arginine for treatment of sickle cell anemia; it is a nutritional supplement

Arginine Supplementation of Sickle Transgenic Mice Leads to a Rapid Decrease in MCHC and Percent Dense Cells and a Slow Increase When Supplementation Is Discontinued.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3579-3579
Author(s):  
Mary E. Fabry ◽  
Zipora Etzion ◽  
Robert M. Bookchin ◽  
Sandra M. Suzuka ◽  
Ronald L. Nagel
Keyword(s):  
Nitric Oxide ◽  
Transgenic Mice ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
High Density ◽  
Red Cells ◽  
Red Cell ◽  
Red Cell Indices ◽  
Plasma Arginine ◽  
Arginine Supplementation

Abstract Nitric oxide (NO) is produced from arginine by nitric oxide synthase (NOS) and is essential to the maintenance of vascular tone. Plasma arginine levels are reduced in sickle cell anemia patients, and we have previously reported that S+S− Antilles mice have lower plasma arginine than control mice (C57BL). Long term arginine supplementation (5% arginine in chow) restored plasma arginine levels in S+S− Antilles mice to that found in C57BL mice, and, in S+S− Antilles mice, MCHC and the percent high density red cells were reduced. Our observation that Ca++-activated K+ channel [K(Ca) channel or Gardos channel] activity is reduced in supplemented vs non-supplemented S+S− Antilles mice can account for reduced red cell density and dense cell formation (Blood99: 1103, 2002). The time course of arginine induced changes in red cell indices in sickle transgenic mice has not yet been studied. Using the Advia 120 Hematology System, we found that, within 7 days after the onset of arginine supplementation, MCHC* (CHCM in the Advia system) fell from 33.4±0.5 g/dL to 31.0±0.2 (mean ±SD, P<0.000002, N=6) and the percent high density red cells (MCHC>37 g/dL) decreased from 10.5±4.3 % to 4.5±1.6 (P<0.01, N=6). MCV rose from 43.6±0.8 fL to 46.4±0.5 (P<0.00003, N=6). Reticulocyte counts and mean corpuscular hemoglobin did not vary significantly. Although plasma arginine levels increase within a few hours of oral administration and persist for only a few hours, no change in red cell indices was observed 7 days after discontinuing arginine supplementation, and the indices slowly returned to baseline levels after 40 days. In summary, MCHC* and the percent high density RBCs decrease significantly within 7 days of the onset of arginine supplementation. When arginine supplementation is withdrawn, the return to baseline values is much slower and required more than 40 days to complete. These observations have important implications for arginine supplementation in sickle cell anemia patients. In particular, the persistence of decreased MCHC* and reduced percent high density RBCs for an extended period of time after supplementation was withdrawn parallels our previously reported observation of persistent improvement of perfusion in sickle transgenic mice after supplementation was withdrawn and suggests that daily administration of arginine may not be necessary once an induction period has passed.

scholarly journals Oral Arginine Therapy As a Novel Adjuvant in the Management of Acute Pain in Children with Sickle Cell Anemia in Nigeria: A Randomized Placebo-Controlled Trial

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 613-613
Author(s):  
Richard Onalo ◽  
Peter Cooper ◽  
Antoinette Cilliers ◽  
Uche Nnebe-Agumadu ◽  
Oluseyi Oniyangi ◽  
...  
Keyword(s):  
Adverse Events ◽  
Sickle Cell ◽  
Controlled Trial ◽  
Crisis Resolution ◽  
Serious Adverse Events ◽  
Children's Hospital ◽  
Pain Scores ◽  
Children’S Hospital ◽  
Plasma Arginine ◽  
Arginine Supplementation

Introduction: Severe vaso-occlusive pain episodes (VOE) are a major cause of morbidityand mortality in sickle cell anemia (SCA). Low arginine bioavailability is associated with pain severity and predicts need for pediatric hospitalization (Morris et al, 2000). Arginine supplementation has opioid-sparing effects and was found to significantly decrease pain scores in children hospitalized with SCA-VOE compared to placebo in a phase-2 randomized placebo-controlled trial (RCT) performed in the United States (US, Morris et al, 2013). Its role to treat acute SCA-related pain in a Sub-Saharan African country is unknown. Objectives: To determine the role of oral arginine as adjuvant in the management of SCA-VOE. Methods: A double-blind RCT of oral L-arginine (100 mg/kg/dose every 8 hours until discharge; up to 5 days/15 doses maximum) was performed in children with SCA hospitalized with severe VOE defined as a Numerical Pain Scale Score (PS) of at least 7 on a scale of 0-10, at one of two hospitals in Abuja, Nigeria. All patients received pain management (both opioids and non-opioid analgesics) per institutional practice. Demographics, clinical characteristics, length of hospital stay (LOS), pain scores, time-to-crisis-resolution (time-to-PS&lt;4), analgesia medications required, and plasma amino acids levels were obtained before and after supplementation. Mean total analgesic medication quantification scale score (MQS), a sensitive measure to quantify analgesic use in patients with SCA, was utilized as previously described (Jacob et al, 2007). Opioid doses were calculated based on morphine equivalents in milligrams (mg). The study was performed after obtaining the National Agency for Food & Drug Administration & Control (NAFDAC) approval, Ref No. NAF/DER/CT/LAG/2017. The protocol was approved by the Human Research Ethics Committees of the University of the Witwatersrand, University of Abuja Teaching Hospital, Abuja & the National Hospital. The study was registered at the Pan African Clinical Trial Registry (PACTR 201611001864290). Results: Sixty-eight children with SCA were recruited, aged 5-17 years (mean: 10.6±0.4 years; 35 children randomized into the arginine arm & 33 into the placebo arm). Baseline characteristics were similar between arms (Table 1). MQS was significantly lower in the arginine group vs. placebo (73 [95% CI: 62-84] vs. 120 [97-143]; p&lt;0.001). By day 5, 54% of children treated with arginine had been discharged compared to 24% in the placebo arm. Although PS were similar in both groups prior to study drug delivery (8.7±1.1 vs. 8.4±1.2, arginine vs placebo; p=0.30), worst reported PS on day 5 were lower in children treated with arginine compared to placebo (1.2±0.4 vs. 3.0±0.5; p&lt;0.0001). The mean rate of PS decline was also greater in the arginine arm vs. placebo (1.5 [1.2-1.8) vs. 1.1 [0.9-1.2] cm/day; p=0.009). Plasma arginine levels increased by 125% vs 29% in the arginine arm vs. placebo; percent increase in arginine bioavailable inversely correlated with MSQ (r=-0.35;p=0.02). There was a non-statistically significant decrease in mean total opioid dose used in the arginine group vs. placebo (3.8 [2.7-4.9] vs 5.1 [3.8-6.5) mg/kg, p = 0.11). Patients receiving arginine had shorter time-to-crisis-resolution (p=0.0216, Fig1A), shorter LOS (p=0.015; Fig1B) and had no serious adverse events. There was 1 death in the placebo group on the second day of admission. There were no differences between groups in development of adverse events, however there was a trend towards more vomiting in the arginine arm compared to placebo (20% vs. 3%, p=0.07). Conclusion: Arginine deficiency plays a role in acute pain requiring hospitalization in Nigerian children with SCA, similar to what has been reported in the US. Plasma arginine levels significantly increased with arginine supplementation, and improved global arginine bioavailability was inversely associated with total analgesia and opioids used in VOE management. Total mean analgesia use and pain scores were lower, while time-to-crisis-resolution and LOS were shorter in children treated with arginine compared to placebo. No serious adverse events occurred in the arginine arm, while rates of adverse events were similar to placebo, providing further support for the safety of arginine therapy in children with SCA. Oral arginine is a promising adjuvant therapy for SCA-VOE management. Disclosures Morris: Pfizer: Consultancy; UCSF-Benioff Oakland: Patents & Royalties: Patents owned by UCSF-Benioff Children's Hospital Oakland regarding biomarkers and therapies that target arginine bioavailability; none are licensed and there is no royalties generated; UCSF-Benioff Children's Hospital Oakland: Patents & Royalties: Patents owned by UCSF-Benioff Children's Hospital Oakland, licensed by Lifetrients, generating royalties for nutritional supplement for autism/apraxia. OffLabel Disclosure: Oral L-arginine for treatment of acute sickle cell disease vaso-occlusive pain

scholarly journals Influence of catastrophizing, anxiety, and depression on in-hospital opioid consumption, pain, and quality of recovery after adult spine surgery

2018 ◽  
Vol 28 (1) ◽  
pp. 119-126 ◽  
Author(s):  
Lauren K. Dunn ◽  
Marcel E. Durieux ◽  
Lucas G. Fernández ◽  
Siny Tsang ◽  
Emily E. Smith-Straesser ◽  
...  
Keyword(s):  
Spine Surgery ◽  
Rating Scale ◽  
Psychological Intervention ◽  
Opioid Consumption ◽  
Anxiety And Depression ◽  
Opioid Use ◽  
Quality Of Recovery ◽  
Pain Scores ◽  
The Impact

OBJECTIVEPerception of perioperative pain is influenced by various psychological factors. The aim of this study was to determine the impact of catastrophizing, anxiety, and depression on in-hospital opioid consumption, pain scores, and quality of recovery in adults who underwent spine surgery.METHODSPatients undergoing spine surgery were enrolled in this study, and the preoperatively completed questionnaires included the verbal rating scale (VRS), Pain Catastrophizing Scale (PCS), Hospital Anxiety and Depression Scale (HADS), and Oswestry Disability Index (ODI). Quality of recovery was assessed using the 40-item Quality of Recovery questionnaire (QoR40). Opioid consumption and pain scores according to the VRS were recorded daily until discharge.RESULTSOne hundred thirty-nine patients were recruited for the study, and 101 completed the QoR40 assessment postoperatively. Patients with higher catastrophizing scores were more likely to have higher maximum pain scores postoperatively (estimate: 0.03, SE: 0.01, p = 0.02), without increased opioid use (estimate: 0.44, SE: 0.27, p = 0.11). Preoperative anxiety (estimate: 1.18, SE: 0.65, p = 0.07) and depression scores (estimate: 1.06, SE: 0.71, p = 0.14) did not correlate with increased postoperative opioid use; however, patients with higher preoperative depression scores had lower quality of recovery after surgery (estimate: −1.9, SE: 0.56, p < 0.001).CONCLUSIONSCatastrophizing, anxiety, and depression play important roles in modulating postoperative pain. Preoperative evaluation of these factors, utilizing a validated tool, helps to identify patients at risk. This might allow for earlier psychological intervention that could reduce pain severity and improve the quality of recovery.

scholarly journals Patients with Sickle Cell Disease in Sicily Have Lower Rates of End Organ Damage, Allo-Immunization and Opioid Prescription Compared to a US Cohort

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3664-3664
Author(s):  
Caterina Minniti ◽  
Concetta Perrotta ◽  
Di Raimondo Francesco ◽  
Alessandra Quota ◽  
James G. Taylor
Keyword(s):  
Health Care ◽  
Disease Severity ◽  
Sickle Cell ◽  
Access To Health Care ◽  
African Ancestry ◽  
Organ Damage ◽  
Opioid Use ◽  
Clinical Complications ◽  
The Us ◽  
Organ Complications

Abstract Background: In developed countries, childhood mortality in sickle cell disease (SCD) is less than 5%, where the SCD morbidity and mortality burden has shifted to adults. As age increases, so do end organ complications like chronic pain. Environmental factors like health economics and genetic factors may influence such outcomes. Recent data from UK, showed higher than expected survival (ASH 2015) in the setting of a national health care system. The Hospital of Gela, Sicily has a well characterized Caucasian SCD population, which also has consistent access to health care via a nationalized system. We hypothesized that traditional disease severity markers including end organ damage, the rate of red blood cell (RBC) alloimmunization and opioid use would be lower in Sicily, compared to a modern US population of African ancestry with inconsistent access to healthcare. Methods: 90 SCD patients in Sicily were followed for over 9 years (2006-2014) to identify clinical complications, alloimmunization rates and survival. Demographics and sickle and alpha globin genotypes were documented. In the US, 632 SCD patients (excluding those with SC) had the same parameters collected as part of the Bethesda Sickle Cell Cohort Study. Laboratory and clinical complications were compared between populations according to phenotype groups (SS/SB0 or SB+ thalassemia). Clinical manifestations included hospitalizations for pain per year, RBC alloimmunization, hydroxyurea prescription rate. Statistical analysis utilized univariate comparisons (t and Chi square tests). Results: In Sicily, 51 patients had SS/SB0 and 28 SB+. All were of self-described Caucasian ancestry. No SC patients were identified in Sicily, therefore all comparisons were limited to SS/SB0 and SB+ thalassemia. Sicilian SS/SB0 patients were older than the US (p<0.0001), had lower AST (p=0.04) and creatinine (p=0.005), and higher HbF (p<0.0001). SB+ patients had similar characteristics (Table 1). Sixteen Sicilian patients (18%) died at a mean age of 53 years (range 31-77). As suggested by these survival data, SCD complications were less frequent for both SS/SB0 and SB+ groups in Sicily compared to the US (Table 2). More Sicilians were prescribed hydroxyurea, especially among those with SB+, although this was not a significant difference. The pain crisis hospitalizations per year was also higher in the US (p=0.008). Consistent with less frequent hospitalizations, only 4 of the Sicilian patients (3 SS/SB0, 1 SB+) were taking long acting opioids, compared to more frequent opioid use in the US. Finally, RBC alloimmunization, another surrogate measure for disease severity, was twice as common in SS/SB0 patients from the US (30%) as in Sicily (14%, p=0.01). Conclusions: These data suggest that end organ complications, like chronic pain and alloimmunization, in self-described Caucasians with uniform access to health care in Sicily, are less common than in a US cohort of adults. These differences could be attributable to access to specialized care, genetic differences in the proportion of African ancestry or environmental factors like more frequent use of preventative therapies like hydroxyurea. RBC alloimmunization in Sicily is significantly lower than reported in the US , but is still higher than observed in thalassemics in Italy. Perhaps this could be explained a matched genetic background between blood donors and recipients in Sicily, as has been suggested as a strategy to reduce RBC alloimmunization in the US. Further studies comparing unique SCD populations from different geographic regions may be helpful to elucidate genetic or environmental risk factors for end organ complications and disease severity. Table 1. Table 1. Table 2. Table 2. Disclosures No relevant conflicts of interest to declare.

Low Fixed Dose Hydroxyurea for the Treatment of Adults with Sickle Cell Disease in Nigeria

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 981-981
Author(s):  
Titilola S. Akingbola ◽  
Bamidele Tayo ◽  
Santosh L. Saraf ◽  
Binal N. Shah ◽  
Chinedu A Ezekekwu ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Low Dose ◽  
Adverse Outcome ◽  
Clinical Malaria ◽  
Fixed Dose ◽  
Cell Disease ◽  
Hemoglobin F ◽  
The Us

Abstract Background: The vast majority of births with sickle cell anemia occur in Africa 1 and early-life mortality, generally before age five years, is as high as 90% 2,3. Hydroxyurea was approved for sickle cell anemia by the US FDA in 1998 but is not commonly used in Africa due to fear of toxicity, lack of awareness and limited availability. Hemoglobin F is a protective factor that decreases severity of sickle cell anemia, and hydroxyurea treatment leads to an increase in hemoglobin F. In the US, hydroxyurea is typically initiated at a dose of 15 mg/kg followed by dose escalations of up to 35 mg/kg if tolerated with a goal of maximal tolerated dose and maximal response in hemoglobin F. Neutropenia and thrombocytopenia are the usual limitations to achieving maximal dose. In the landmark Multicenter Study of Hydroxyurea, the clinical response to hydroxyurea correlated strongly with a reduction in the neutrophil count as well as an increase in the fetal hemoglobin concentration as reflected in percentage of F cells. A striking decrease in pain crises was observed in the first three months of therapy, before dose escalation and before maximal increase in hemoglobin F levels 4. Furthermore, hydroxyurea in the range of 10-15.9 mg/kg/day was reportedly effective in decreasing the frequency of pain episodes in children and adolescents in Oman 5, and hydroxyurea 10 mg/kg/day decreased pain episodes in children and adults with sickle cell anemia in India 6. From these perspectives, we reasoned that a fixed dose of hydroxyurea 10 mg/kg/day is reasonable to investigate in the African setting where the safety in relationship to the resources and infectious exposures is not known. Methods: We assigned 48 sickle cell anemia patients to hydroxyurea 500 mg/day for 24 weeks to determine safety and efficacy; 28 had high-risk disease based on hemoglobin F&lt;8.6% and absence of alpha-thalassemia. We defined a clinically meaningful adverse outcome category as ≥10% of patients developing platelets &lt;50,000/uL, granulocytes &lt;500/uL, clinical malaria and/or active tuberculosis. Picking up refills every four weeks was the adherence metric. We analyzed the results on an intent-to-treat basis. Results: The median (interquartile range) age was 25 (22-27) years and the median hydroxyurea dose 9.8 (9.1-10.4) mg/kg per day. The patients complied with treatment for a median of 20 (16-24) weeks. Four (8.3%) developed a pre-specified adverse outcome: clinical malaria (N=2), thrombocytopenia in combination with malaria (N=1), pulmonary tuberculosis (N=1). During therapy the median hemoglobin increased by 9.0 g/L, mean corpuscular volume by 11.2 fL and body weight by 3.0 kg while median white blood cells declined by 2600 per uL and platelets by 127,000 per uL (P&lt;0.001). The median hemoglobin F increased from 4.1% (2.3-6.3%) at baseline (N=27) to 8.5% (6.3-12.9%) during therapy (N=24) (P&lt;0.001). Conclusion: Our results suggest that low, fixed-dose dose hydroxyurea for sickle cell anemia in Nigeria is associated with a low adverse outcome rate and with improvements in blood counts, hemoglobin F and body weight. The effects on vaso-occlusive episodes and on the risks of recrudescent tuberculosis and malaria-associated thrombocytopenia should be assessed in further studies. Acknowledgment: Supported by a grant from the Doris Duke Foundation. References 1. Williams TN, Obaro SK. Sickle cell disease and malaria morbidity: a tale with two tails. Trends Parasitol 2011;27:315-20. 2. Grosse SD, Odame I, Atrash HK, Amendah DD, Piel FB, Williams TN. Sickle cell disease in Africa: a neglected cause of early childhood mortality. Am J Prev Med 2011;41:S398-405. 3. Makani J, Cox SE, Soka D, et al. Mortality in sickle cell anemia in Africa: a prospective cohort study in Tanzania. PLoS One 2011;6:e14699. 4. Charache S, Barton FB, Moore RD, et al. Hydroxyurea and sickle cell anemia. Clinical utility of a myelosuppressive "switching" agent. The Multicenter Study of Hydroxyurea in Sickle Cell Anemia. Medicine (Baltimore) 1996;75:300-26. 5. Sharef SW, Al-Hajri M, Beshlawi I, et al. Optimizing Hydroxyurea use in children with sickle cell disease: low dose regimen is effective. Eur J Haematol 2013. 6. Patel DK, Mashon RS, Patel S, Das BS, Purohit P, Bishwal SC. Low dose hydroxyurea is effective in reducing the incidence of painful crisis and frequency of blood transfusion in sickle cell anemia patients from eastern India. Hemoglobin 2012;36:409-20. Disclosures Ezekekwu: American Society of Hematology: Other: The Visitor training program was sponsored by ASH. Hsu: AstraZeneca steering committee for HESTIA trial: Research Funding. Gordeuk: Emmaus Life Sciences: Consultancy.

scholarly journals Burden of neurological and neurocognitive impairment in pediatric sickle cell anemia in Uganda (BRAIN SAFE): a cross-sectional study

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Nancy S. Green ◽  
Deogratias Munube ◽  
Paul Bangirana ◽  
Linda Rosset Buluma ◽  
Bridget Kebirungi ◽  
...  
Keyword(s):  
Brain Injury ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Cross Sectional Study ◽  
Neurocognitive Impairment ◽  
Sectional Study ◽  
Cross Sectional ◽  
Neurocognitive Dysfunction ◽  
The Impact ◽  
Prior Stroke

Abstract Background Children with sickle cell anemia (SCA) are highly susceptible to stroke and other manifestations of pediatric cerebral vasculopathy. Detailed evaluations in sub-Saharan Africa are limited. Methods We aimed to establish the frequency and types of pediatric brain injury in a cross-sectional study at a large SCA clinic in Kampala, Uganda in a randomly selected sample of 265 patients with HbSS ages 1–12 years. Brain injury was defined as one or more abnormality on standardized testing: neurocognitive impairment using an age-appropriate test battery, prior stroke by examination or transcranial Doppler (TCD) velocities associated with stroke risk in children with SCA (cerebral arterial time averaged mean maximum velocity ≥ 170 cm/second). Results Mean age was 5.5 ± 2.9 years; 52.3% were male. Mean hemoglobin was 7.3 ± 1.01 g/dl; 76.4% had hemoglobin < 8.0 g/dl. Using established international standards, 14.7% were malnourished, and was more common in children ages 5–12. Overall, 57 (21.5%) subjects had one to three abnormal primary testing. Neurocognitive dysfunction was found in 27, while prior stroke was detected in 15 (5.7%). The most frequent abnormality was elevated TCD velocity 43 (18.1%), of which five (2.1%) were in the highest velocity range of abnormal. Only impaired neurocognitive dysfunction increased with age (OR 1.44, 95%CI 1.23–1.68), p < 0.001). In univariate models, malnutrition defined as wasting (weight-for-height ≤ −2SD), but not sex or hemoglobin, was modestly related to elevated TCD (OR 1.37, 95%CI 1.01–1.86, p = 0.04). In adjusted models, neurocognitive dysfunction was strongly related to prior stroke (OR 6.88, 95%CI 1.95–24.3, p = .003) and to abnormal TCD (OR 4.37, 95%CI 1.30, p = 0.02). In a subset of 81 subjects who were enriched for other abnormal results, magnetic resonance imaging and angiography (MRI/MRA) detected infarcts and/or arterial stenosis in 52%. Thirteen subjects (25%) with abnormal imaging had no other abnormalities detected. Conclusions The high frequency of neurocognitive impairment or other abnormal results describes a large burden of pediatric SCA brain disease in Uganda. Evaluation by any single modality would have underestimated the impact of SCA. Testing the impact of hydroxyurea or other available disease-modifying interventions for reducing or preventing SCA brain effects is warranted.

The Impact of Alvimopan on Return of Bowel Function After Major Spine Surgery – A Prospective, Randomized, Double-Blind Study

Neurosurgery ◽  
2019 ◽  
Vol 85 (2) ◽  
pp. E233-E239
Author(s):  
Lauren K Dunn ◽  
Robert H Thiele ◽  
Michelle C Lin ◽  
Edward C Nemergut ◽  
Marcel E Durieux ◽  
...  
Keyword(s):  
Spine Surgery ◽  
Bowel Movement ◽  
Bowel Function ◽  
Blind Study ◽  
Double Blind Study ◽  
Opioid Use ◽  
Double Blind ◽  
Pain Scores ◽  
Significant Difference ◽  
The Impact

Abstract BACKGROUND Pain management following major spine surgery requires high doses of opioids and is associated with a risk of opioid-induced constipation. Peripheral mu-receptor antagonists decrease the gastrointestinal complications of perioperative systemic opioid administration without antagonizing the analgesic benefits of these drugs. OBJECTIVE To investigate the impact of alvimopan in opioid-naive patients undergoing major spine surgery. METHODS Patients undergoing >3 levels of thoracic and/or lumbar spine surgery were enrolled in this prospective, randomized, double-blind study to receive either alvimopan or placebo prior to and following surgery. Opioid consumption; pain scores; and time of first oral intake, flatus, and bowel movement were recorded. RESULTS A total of 24 patients were assigned to the active group and 25 were assigned to the placebo group. There was no significant difference in demographics between the groups. Postoperatively, the alvimopan group reported earlier time to first solid intake [median (range): alvimopan: 15 h (3-25) vs placebo: 17 h (3-46), P < .001], passing of flatus [median (range): alvimopan: 22 h (7-63) vs placebo: 28 h (10-58), P < .001], and first bowel movement [median (range): alvimopan: 50 h (22-80) vs placebo: 64 h (40-114), P < .001]. The alvimopan group had higher pain scores (maximum, minimum, and median); however, there was no significant difference between the groups with postoperative opioid use. CONCLUSION This study shows that the perioperative use of alvimopan significantly reduced the time to return of bowel function with no increase in postoperative opioid use despite a slight increase in pain scores.

Hematopoietic Stem Cell Transplantation in Nigerian Children with Sickle Cell Anemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4598-4598
Author(s):  
Antonella Isgro ◽  
Javid Gaziev ◽  
Pietro Sodani ◽  
Marco Andreani ◽  
Manuela Testi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Ischemic Stroke ◽  
Hematopoietic Stem Cell Transplantation ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Conditioning Regimen ◽  
Myeloablative Conditioning ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Nigerian Children

Abstract Introduction: Sickle cell anemia (SCA) remains associated with high risks of morbidity and early death. Children with SCA are at high risk for ischemic stroke and transient ischemic attacks, secondary to intracranial arteriopathy involving carotid and cerebral arteries. Children with Black African variant SCA are prone to invasive infections caused by S. pneumonia, H. influenzae and Plasmodium falciparum (in malarias areas). In Africa, malaria contributes substantially to the early mortality of patients with SCA. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for SCA. We report our experience with transplantation in a group of Nigerian children affected by SCA. Patients and Methods: This study included 36 consecutive SCA patients who underwent bone marrow transplantation from human leukocyte antigen (HLA)-identical sibling donors between 2010 and 2015 following a myeloablative-conditioning regimen. Patients received fludarabine (30 mg/m2/day) for 5 days and a conditioning regimen including targeted intravenous busulfan (14 mg/kg total dose) and cyclophosphamide (200 mg/kg total dose). Blood samples were collected in different Nigerian Hospitals and shipped to the Laboratory of the IME Foundation in Italy where were processed for DNA preparation on a fully automated system (Maxwell, Promega, Madison, WI). Low resolution HLA-A, -B, -C, -DRB1 and -DQB1 typing was performed using the polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) technique (LABType - One Lambda, Canoga Park, CA). Results: The median patient age was 10 years (range 2-17 years). Before transplantation, seventeen patients had recurrent, painful, vaso-occlusive crisis; twelve patients had recurrent painful crisis in association with acute chest syndrome; three patients experienced ischemic stroke and recurrent vaso-occlusive crisis; two patients experienced ischemic stroke; one patient exhibited leucocytosis; and one patient exhibited priapism. Of the 36 patients, 33 survived without sickle cell disease, with Lansky/Karnofsky scores of 100, following a myeloablative-conditioning regimen. The probabilities of survival, SCA-free survival, and transplant-related mortality after transplant were 92%, 92%, and 8%, respectively. All surviving patients remained free of any SCA-related events after transplantation. Within the frame of the HSCT program for the treatment of SCA, a total of 124 Nigerian families with 2 to 11 children (average 2.5) were typed for five HLA loci (A, B, C, DRB1 and DQB1) and the phased genotypes were unambiguously determined. Thirty-six percent of the patients had at his disposal within the family a HLA compatible sibling. Conclusion: The protocols used for the preparation to the transplant in thalassemia are very effective also in the other severe hemoglobinopathy as in the sickle cell anemia with more than 90% disease free survival. If a SCA patient has a HLA identical family member, the allogeneic cellular gene therapy through the transplantation of the hematopoietic stem cells should be performed as soon as possible, before the disease progresses through a treatment-related irreversible organ damage. Disclosures No relevant conflicts of interest to declare.

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