A Cost-Effective Technique for Spinal Instrumentation in the Treatment of Adolescent Idiopathic Scoliosis.

Surgical treatment for adolescent idiopathic scoliosis (AIS) has evolved over the past decades to the point where instrumented arthrodesis with all pedicle screw and rod constructs is commonplace. Although these constructs provide superb correction and fixation, their financial burden is substantial. Here, we present a more cost-effective technique using a combination of pedicle screws (serving as the construct base), a sagittal precontoured unit rod, and sublaminar wires to provide segmental correction for the surgical treatment of AIS. Retrospective analyses of 42 patients treated with this construct were reviewed with a minimum 2-year follow-up. Correction in both coronal and sagittal planes was assessed radiographically and blood loss, operative time, complications, and cost were reviewed from hospital records. We conclude that this technique provides comparable correction to all pedicle screw constructs with similar blood loss and operative time, but with substantially decreased implant cost. The mean implant cost was $8910.83 ± $184.26.

Management of pediatric type III supracondylar humerus fractures in the United States: results of a national survey of pediatric orthopaedic surgeons.

BACKGROUND: Supracondylar humerus fractures are common injuries in the pediatric population. The most severe, type III injuries, have seen the most debate on treatment regimens. Traditionally, these fractures were treated as surgical emergencies, most often fixed with percutaneous pinning in a cross-pin configuration. The recent literature shows that delayed fixation is comparable to emergent fixation as long as there is no vascular compromise with the injury. METHODS: A short survey was sent to Pediatric Orthopaedic Society of North America (POSNA) members using an online survey and questionnaire service. The purpose of the survey was to establish an overview of current practices in the United States concerning treatment of type III supracondylar humerus fractures and the influence of the recent literature on the management of these injuries. RESULTS: A total of 309 members, representing a wide range of locations and years in practice, responded to our survey. About 81% preferred to splint type III supracondylar humerus fractures and plan for fixation the following morning, assuming there was no issue necessitating emergent fixation. The preferred method of percutaneous fixation was fairly evenly distributed between cross-pin configuration (30%), 2 lateral pins (33%), and 3 lateral pins (37%). About 56% of those surveyed stated that the recent literature showing comparable outcomes with 2 lateral pins versus a cross-pin configuration had not changed their approaches to management of these fractures concerning the method of fixation. CONCLUSIONS: The trend in management of type III supracondylar humerus fractures in children is progressing toward delayed treatment and lateral pin configuration. The results provide an overview of the current practice of POSNA members concerning management of these fractures. We believe this information is beneficial to both pediatric-trained and nonpediatric-trained orthopaedic surgeons to help guide their decisions when dealing with these injuries. LEVEL OF EVIDENCE: This study is a Level V Therapeutic Study reviewing trends in the management of type III supracondylar humerus fractures in children. The previously described experts represent various levels of expertise in their preferred method of fixation.

Primary pyomyositis of the pelvis in children: a retrospective review of 8 cases.

Primary pyomyositis of the pelvic musculature is a condition rarely seen in temperate climates, although its frequency has been increasing in the United States. The condition should be considered in the initial differential diagnosis of an adolescent presenting with fever, difficulty ambulating, and hip pain. This is a retrospective review of 8 cases of primary pelvic pyomyositis in patients aged 18 years or younger who were treated at the Children's Medical Center in Augusta, Georgia. The site of infection was the obturator internus in the majority of the cases (5). The site was the gluteus, iliopsoas, and iliacus in 1 case each. Four patients who were diagnosed early responded to intravenous antibiotics with no need for further intervention. Two patients required incision and drainage of an abscess combined with antibiotics. Two patients had prolonged hospital courses requiring intensive unit care and mechanical ventilation. Blood cultures were positive in 87.5% of patients, and all patients presented with elevated acute phase reactants. One of the most difficult diagnostic aspects of presentation is an inconclusive symptom profile. It is noteworthy that patients with pelvic pyomyositis may present with limited range of motion in a specific plane (the motion placing the infected muscle on stretch) vs global limited range of motion of the joint as is commonly seen in septic arthritis. Early diagnosis is essential to prevent systemic illness and complications associated with this condition. Magnetic resonance imaging with gadolinium is helpful to diagnose and guide treatment.

The role of secretory phospholipase A2 in acute chest syndrome.

Acute chest syndrome (ACS) is the leading cause of death in sickle cell disease. Severe ACS often develops in the course of a vasoocclusive crisis (VOC), and frequently involves pulmonary fat embolism. Secretory phospholipase A2 (sPLA2), a potent inflammatory mediator, is elevated in ACS, and sPLA2 levels in serum or plasma predict impending ACS. In addition sPLA2 may play a major role in the actual damage to the lung resulting in a new pulmonary infiltrate on chest radiography, respiratory symptoms, and ultimately alveolar collapse and the impairment of gas exchange. The data indicate that measurement of sPLA2 can be useful in alerting the clinician to patients with impending ACS, and suggest that instituting early therapies based on sPLA2 levels, including inhibition of sPLA2 activity, may be useful to prevent or reduce the clinical morbidity of ACS in sickle cell disease.

Impact of chronic transfusion on incidence of pain and acute chest syndrome during the Stroke Prevention Trial (STOP) in sickle-cell anemia.

OBJECTIVE: The Stroke Prevention Trial (STOP) demonstrated that chronic transfusion is highly effective in reducing the risk of stroke in children with sickle-cell disease and an abnormal transcranial Doppler ultrasonography examination result. Our objective was to determine whether chronic transfusion therapy reduces the incidence of pain and acute chest syndrome. METHODS: During STOP, 130 children with sickle-cell anemia or sickle beta(0)-thalassemia and abnormal transcranial Doppler ultrasonography examination result were randomly assigned to chronic transfusion (n = 63) or observation (n = 67). In addition to monitoring for stroke, nonneurologic sickle-cell complications were identified and recorded. RESULTS: Mean age at STOP study entry was 8.3 +/- 3.3 years, and mean follow-up was 19.6 +/- 6.5 months. Hospitalization rates (based on intent-to-treat analysis) for acute chest syndrome were 4.8 and 15.3 per 100 patient-years (P =.0027) and for pain were 16.2 and 27.6 per 100 patient-years (P =.13) in the chronic transfusion and observed groups, respectively. If analyzed according to treatment actually received, the difference in pain rate becomes significant (9.7 vs 27.1 events per 100 patient-years, P =.014), and transfusion remains protective from acute chest syndrome (2.2 vs 15.7 events per 100 patient-years, P =.0001). CONCLUSIONS: Compliance with aggressive chronic transfusion reduces the frequency of acute chest syndrome and pain episodes.

A novel multilocus genotyping assay to identify genetic predictors of stroke in sickle cell anaemia.

We describe a novel multilocus genotyping assay permitting simultaneous identification of 60 candidate markers for stroke in sickle cell anaemia (SCA). Based on cerebral magnetic resonance imaging (MRI), 69 patients were divided into stroke and control groups. The variant allele, CBS 278thr, showed protection from stroke, whereas the apoE3 allele showed a trend towards association with increased stroke risk. Several other variant alleles [TNFalpha (-308)A, CETP (-628)A, apoCIII (-641)A] showed a trend towards significant associations with stroke risk. These preliminary results on a small group of patients suggest that a multilocus genotyping assay may be valuable in identifying genes that increase the risk of stroke in SCA.

Characterization of the phosphatidylserine-exposing subpopulation of sickle cells.

Phosphatidylserine (PS), exclusively present in the inner monolayer of the normal red blood cell (RBC) membrane, is exposed in subpopulations of sickle cells. PS-exposing RBCs were found predominantly among the densest and the very light sickle cells. Within the light RBC fraction, PS exposure was found on reticulocytes, transferrin receptor-expressing reticulocytes, and mature RBCs. The last subset contained low-density valinomycin-resistant RBCs, previously shown to have high Na(+) and low K(+) content. This subpopulation contained the highest percentage of PS-exposing cells. The PS-exposing sickle cells did not show the sustained high cytosolic Ca(++) levels that have been shown to activate scramblase activity. Data from this study indicate that PS exposure can occur at different stages in the life of the sickle RBC and that it correlates with the loss of aminophospholipid translocase activity, the only common denominator of the PS-exposing cells. The additional requirement of scramblase activation may occur during transient increases in cytosolic Ca(++). (Blood. 2001;98:860-867)

Arginine therapy: a novel strategy to induce nitric oxide production in sickle cell disease.

To determine the effects of L-arginine (L-Arg) supplementation on nitric oxide metabolite (NOx) production, oral L-Arg was given to normal controls, sickle cell disease (SCD) patients at steady state and SCD patients hospitalized with a vaso-occlusive crisis (VOC). L-Arg (0.1 g/kg) increased NOx formation by 18.8 +/- 68% in normal controls, whereas steady-state SCD patients demonstrated a paradoxical decrease in NOx of -16.7 +/- 4% (P = 0.004). In contrast, patients with VOC demonstrated a dramatic increase in NOx production by +77.7 +/- 103%, a response that was dose dependent. L-Arg appears to be the rate-limiting step in NOx production during VOC. Oral arginine may therefore benefit SCD patients by inducing an increase in NO production during VOC.

Patterns of arginine and nitric oxide in patients with sickle cell disease with vaso-occlusive crisis and acute chest syndrome.

PURPOSE: Our objective was to evaluate L-arginine and nitric oxide metabolite (NOx) levels in children with sickle cell disease (SCD) at steady-state and during vaso-occlusive crisis (VOC). Because alterations in nitric oxide production may have an important role in the pathophysiology of SCD, our second aim was to determine if a relationship exists between these levels and vaso-occlusive crisis (VOC). PATIENTS AND METHODS: Plasma L-arginine and serum NOx levels were examined in 36 patients with SCD with 39 episodes of VOC and 10 children with SCD at steady-state. Daily levels were obtained in children requiring hospitalization. RESULTS: Steady-state L-arginine levels were normal in children with SCD. L-arginine levels were low, however, in children with VOC (37.4 +/- 2.7 vs. 53.6 +/- 4.6 micromol/L; P = 0.008) but returned to baseline during hospitalization. In contrast, NOx levels were normal at presentation but decreased during hospitalization for both patients with VOC and patients with acute chest syndrome (ACS) (21.1 +/- 2.0, 17.4 +/- 2.4, and 12.3 +/- 1.6 micromol/L, respectively; P < 0.05). In the patients with VOC who had ACS develop, L-arginine decreased to the lowest levels at the time of the ACS diagnosis, correlating with decreasing NOx levels. CONCLUSION: These data suggest that there may be a relationship between the L-arginine-nitric oxide pathway and vaso-occlusion in SCD. Low arginine levels during VOC could reflect a state of acute substrate depletion that results in a decrease in nitric oxide production.

Changing outcome of homozygous alpha-thalassemia: cautious optimism.

Only a few long-term survivors of homozygous alpha-thalassemia, a usually fatal condition, have been reported. The authors present a surviving infant with this disorder and discuss the complications, treatments, and implications of this genetic hemoglobinopathy. The child had no antenatal intervention and has been treated with regular transfusions. She has had normal growth and development and is currently 2.5-years-old. A literature review of survivors with Bart hemoglobinopathy reveals an intense perinatal course and a great prevalence of congenital urogenital and limb defects. Advances in antenatal diagnosis, intrauterine intervention, and postnatal treatments have resulted in extended survival of children with congenital defects that until recently were considered invariably fatal. Transfusion and chelation therapy and bone marrow transplantation provide long-term treatment and potential curative options.

Secretory phospholipase A(2) predicts impending acute chest syndrome in sickle cell disease.

Acute chest syndrome (ACS) is the leading cause of death in sickle cell disease. Severe ACS often develops in the course of a vaso-occlusive crisis (VOC), but currently there are no predictors for its development. Secretory phospholipase A(2) (sPLA(2)), a potent inflammatory mediator, is elevated in ACS, and previous work suggests that sPLA(2) predicts impending ACS. We prospectively evaluated sPLA(2) concentration during 21 admissions for VOC; 6 of these patients went on to develop ACS. Elevation of sPLA(2) was detected all 6 patients 24 to 48 hours before ACS was clinically diagnosed. Adding the requirement for fever raised the specificity of sPLA(2) to 87% while retaining 100% sensitivity. These data indicate that sPLA(2) can be useful in alerting the clinician to patients with impending ACS. In addition, sPLA(2) may be useful for instituting early therapies to prevent or reduce the clinical morbidity of ACS.

Use of hydroxyurea in children ages 2 to 5 years with sickle cell disease.

The efficacy and side effects of hydroxyurea in young children with sickle cell disease are unknown. The authors followed-up eight young children (mean age 3.7 years) during therapy with hydroxyurea for an average of 137 weeks. Total and fetal hemoglobin levels rose with hydroxyurea therapy. Hospital admission rates and total hospital days decreased during hydroxyurea therapy. No unexpected toxicity occurred, and growth and development were unaffected. This pilot study suggests that hydroxyurea is safe and effective in young children with sickle cell disease.

Evidence for HLA-related susceptibility for stroke in children with sickle cell disease.

Cerebral infarction occurs in one quarter of all children with sickle cell anemia (SCA). There is an increased risk of stroke in siblings with SCA, suggesting genetic factors may influence risk of stroke. The authors investigated whether HLA type was associated with risk of stroke in children with SCA. Fifty-three patients with SCA underwent complete HLA typing at both HLA class I (HLA-A, B) and HLA class II (HLA-DR, DQ, DP) loci. Of the 53 patients, 22 had magnetic resonance imagining (MRI)-documented evidence of cerebral infarction, and the remaining 31 patients had negative MRI scans. Comparison of the results of HLA typing between the SCA patients with a positive and those with a negative MRI documented that the 2 groups differed with respect to the class I HLA-B (P =.012), and the class II HLA-DRB1 (P =.0008) and DQB1 (P =.029). Susceptibility associations at the HLA-DRB1 locus included both DR3 alleles, where DRB1*0301 and *0302 were both associated with an increased risk of stroke. Protective associations were found in the DR2 group, where DRB1*1501 was protective for stroke. DQB1*0201, which is in linkage disequilibrium with DRB1*0301, was also associated with stroke. Similarly, DQB1*0602, in linkage disequilibrium with DRB1*1501, was protective. Specific HLA alleles may influence the risk of stroke in children with SCA. HLA typing may prove useful in identifying SCA patients at higher risk for stroke.

Hydroxyurea and sodium phenylbutyrate therapy in thalassemia intermedia.

Hydroxyurea (HU) and sodium phenylbutyrate (SPB) have been shown to increase fetal hemoglobin (Hb F) levels in patients with thalassemia intermedia. The reported effects of these agents in increasing total Hb, however, have been inconsistent and there have been no studies on the combination of these medications. We describe the clinical response, as determined by increases in total Hb and decreased transfusion needs, in five patients with thalassemia intermedia treated with HU alone or in combination with SPB. All of the patients responded with increased levels of Hb F, but the responses in total Hb varied. Of the five patients, two had a marked response in total Hb in excess of 3 g/dl, two responded modestly with an increase in total Hb of 1-2 g/dl, and one did not respond. Prolonged responses were achieved with low doses of HU (3-10 mg/kg/day) and higher doses were associated with mild reversible hematologic or hepatic toxicity and no further increases in Hb. Sodium phenylbutyrate was added to treatment with HU in two patients, but failed to produce an increase in total Hb despite increasing Hb F levels. Of the four patients who responded to HU with an increase in total Hb, all reported symptomatic improvement and three have not required further transfusions. We conclude that low-dose HU therapy in patients with thalassemia intermedia may increase total Hb levels sufficiently to eliminate the need for transfusions. We, therefore, recommend a trial of HU for thalassemia intermedia patients in whom chronic transfusion therapy is being contemplated.

Effects of red blood cell transfusion on resting energy expenditure in adolescents with sickle cell anemia.

BACKGROUND: Previous studies indicate that resting energy expenditure is elevated in children with sickle cell anemia, possibly caused in part by hemolysis and increased erythropoietic activity. The purpose of the present investigation was to determine whether erythrocyte transfusion normalizes resting energy expenditure in sickle cell anemia. METHODS: Five adolescents with sickle cell anemia (12-16 years old; 4 boys, 1 girl) were studied before and 1 week after erythrocyte transfusion before elective surgery or at the initial transfusion for growth failure. Resting energy expenditure was measured by indirect calorimetry, and laboratory measures were determined by routine, validated methods. Data comparisons were by nonparametric analysis. RESULTS: After erythrocyte transfusion, total hemoglobin levels increased (difference (D) = 15 g/l; p < 0.05), whereas hemoglobin S (D = -0.36; p < 0.05) and reticulocyte count (D = -0.12; p < 0.05) decreased. Mean pretransfusion resting energy expenditure was elevated to 124% above predicted levels (p < 0.05) and increased further to 134% above prediction (p < 0.05 vs. pretransfusion levels). Plasma triiodothyronine (T3) levels increased (D = 0.17 nmol/l; p < 0.05), reverse T3 (rT3) levels tended to decline (D = -0.04 nmol/l; p = 0.14), and rT3/T3 decreased (D = -0.03; p < 0.05). Plasma insulin-like growth factor-I (IGF-I) levels were low-normal before transfusion and did not change, despite the change in resting energy expenditure. CONCLUSIONS: The results confirm that resting energy expenditure is elevated in patients with sickle cell anemia. However, resting energy expenditure further increased after transfusion, despite decreased erythropoietic activity. A posttransfusion decrease in rT3/T3 may contribute to the increased resting energy expenditure. That there was no change in IGF-I implies that the growth hormone-IGF system is not involved in posttransfusion regulation of resting energy expenditure. Therefore, our data are not consistent with the hypothesis that increased resting energy expenditure in sickle cell anemia is directly related to erythropoietic activity. The mechanisms by which resting energy expenditure increases after transfusion in sickle cell anemia require additional investigation.

Clinician assessment for acute chest syndrome in febrile patients with sickle cell disease: is it accurate enough?

STUDY OBJECTIVE: To determine whether the use of empiric chest radiography (CXR) is of significant value in detecting clinically unsuspected acute chest syndrome (ACS) in febrile patients with sickle cell disease (SCD). METHODS: Patients with SCD presenting to the emergency department and hematology clinic with temperature greater than or equal to 38 degrees C were prospectively evaluated using a physician-completed questionnaire. The questionnaire included inquiries into the patient's physical signs and symptoms and the physician's clinical impression for the presence of ACS. The questionnaire was completed before obtaining CXR results in all patients. RESULTS: Seventy-three patients with SCD with 96 febrile events were evaluated over a 1-year period. Twenty-four percent (23/96) of the patients had CXR evidence of ACS. On the basis of the questionnaire data, 61% (14/23) of ACS cases were not clinically suspected by the evaluating physician before obtaining CXR. Comparing the patients with and without ACS revealed that, with the exception of splinting (4/23 [17%] versus 0/73 [0%]), no symptom or physical examination finding helped to identify which patients had ACS. Fifty-seven percent of patients with ACS had completely normal findings on physical examination. The presentation of patients with clinically detected versus clinically unsuspected ACS also did not differ significantly. Length of hospitalization, oxygen use, and need for transfusion were the same in both the unsuspected and detected ACS groups. Overall physician sensitivity for predicting ACS was only 39%, and diagnostic accuracy did not improve significantly with increasing levels of pediatric training. CONCLUSION: ACS is common in patients with SCD who present with fever and was grossly underestimated by evaluating physicians. History and physical examination appear to be of little value in defining which febrile patients require CXR. In view of the mortality and morbidity associated with ACS, empiric CXR should be considered when evaluating a febrile patient with SCD.

The hemoglobin E syndromes.

Heterozygotes and homozygotes for HbE (beta 26, GAG-AAG, Glu-Lys) are microcytic, minimally anemic, and asymptomatic. The microcytosis is attributed to the beta thalassemic nature of the beta E gene, whereas the in vitro instability of HbE does not contribute to the phenotype. However, the compound heterozygote state HbE/beta thalassemia results in a variable, and often severe anemia, with the phenotype ranging from transfusion dependence to a complete lack of symptoms. This has been well documented in Thailand, but the basis of the interaction and the cause of the variability remains unexplained. We have studied 50 HbE/beta thalassemics from the UK and 16 from Oakland, CA and assessed the role of HbE instability. Time-course globin chain synthesis experiments have shown that instability is not an important factor in the steady state, but that at 41 degrees C newly synthesized Hb molecules are unstable. We have identified one family in which HbE interacts with pyrimidine 5' nucleotidase deficiency to cause severe anemia with Hb instability. The UK individuals, mostly of Bengali origin, have Hb's from 4.5-11 g/dl. The beta thalassemia mutation, alpha thalassemia and the Xmn 1 G gamma polymorphism do not explain this variability, but the relative and absolute amounts of HbF correlate significantly with total Hb. The Oakland individuals, mostly from Southeast Asia, show similar variation in Hb, which again is largely unexplained.

Whole blood tissue factor procoagulant activity is elevated in patients with sickle cell disease.

We developed a simple assay for the measurement of tissue factor procoagulant activity (TF PCA) in whole blood samples that avoids the need for mononuclear cell isolation. This method combines convenience of sample collection and processing with a high degree of sensitivity and specificity for TF. Using this method, we have determined that TF PCA is detectable in whole blood samples from normal individuals, which is itself a novel observation. Essentially all PCA could be shown to be localized in the mononuclear cell fraction of blood. Compared with controls, whole blood TF levels were significantly (P < .000001) elevated in patients with sickle cell disease (SCD), regardless of the subtype of hemoglobinopathy (SS or SC disease). No significant difference in TF PCA was observed between patients in pain crisis compared with those in steady-state disease. Because TF functions as cofactor in the proteolytic conversion of FVII to FVIIa in vitro, it was expected that an increase in circulating TF PCA would lead to an increased in vivo generation of FVIIa. On the contrary, FVIIa levels were actually decreased in the plasma of patients with SCD. Plasma TF pathway inhibitor (TFPI) antigen levels were normal in SCD patients, suggesting that accelerated clearance of FVIIa by the TFPI pathway was not responsible for the reduced FVIIa levels. We propose that elevated levels of circulating TF PCA may play an important role in triggering the activation of coagulation known to occur in patients with SCD. Because TF is the principal cellular ligand for FVIIa, it is possible that increased binding to TF accounts for the diminished plasma FVIIa levels.

Acute chest syndrome and sickle cell disease.

Acute chest syndrome (ACS) is the presence of a new pulmonary infiltrate in combination with fever or respiratory symptoms in a patient with sickle cell disease. ACS is the leading cause of death in sickle cell disease, and many patients suffer from multiple, severe episodes. Age has a striking effect on the clinical course and outcome of ACS, with children having milder disease that often is infectious. Adults often have severe disease, and pulmonary fat embolism is frequently a component of severe ACS. Rapid diagnosis and appropriate therapy including antibiotics for atypical infections, fluids, aerosolized beta agonists, and adequate pain control are necessary to reduce morbidity. Transfusion is indicated in hypoxic patients and can be used to prevent recurrent episodes. As the pathophysiology of ACS is further delineated, new treatment strategies will be investigated.