Deanne Soares

Prevention of conversion to abnormal transcranial Doppler with hydroxyurea in sickle cell anemia: A Phase III international randomized clinical trial

Children with sickle cell anemia (SCA) and conditional transcranial Doppler (TCD) ultrasound velocities (170–199 cm/sec) may develop stroke. However, with limited available clinical data, the current standard of care for conditional TCD velocities is observation. The efficacy of hydroxyurea in preventing conversion from conditional to abnormal TCD (≥200 cm/sec), which confers a higher stroke risk, has not been studied prospectively in a randomized trial. Sparing Conversion to Abnormal TCD Elevation (SCATE #NCT01531387) was a National Heart, Lung, and Blood Institute‐funded Phase III multicenter international clinical trial comparing alternative therapy (hydroxyurea) to standard care (observation) to prevent conversion from conditional to abnormal TCD velocity in children with SCA. SCATE enrolled 38 children from the United States, Jamaica, and Brazil [HbSS (36), HbSβ0‐thalassemia (1), and HbSD (1), median age = 5.4 years (range, 2.7–9.8)]. Because of the slow patient accrual and administrative delays, SCATE was terminated early. In an intention‐to‐treat analysis, the cumulative incidence of abnormal conversion was 9% (95% CI = 0–35%) in the hydroxyurea arm and 47% (95% CI = 6–81%) in observation arm at 15 months (P = 0.16). In post hoc analysis according to treatment received, significantly fewer children on hydroxyurea converted to abnormal TCD velocities when compared with observation (0% vs. 50%, P = 0.02). After a mean of 10.1 months, a significant change in mean TCD velocity was observed with hydroxyurea treatment (−15.5 vs. +10.2 cm/sec, P = 0.02). No stroke events occurred in either arm. Hydroxyurea reduces TCD velocities in children with SCA and conditional velocities. Am. J. Hematol. 90:1099–1105, 2015.

Prevention of conversion to abnormal tcd with hydroxyurea in sickle cell anemia: A phase III international randomized clinical trial

Children with sickle cell anemia (SCA) and conditional transcranial Doppler (TCD) ultrasound velocities (170–199 cm/sec) may develop stroke. However, with limited available clinical data, the current standard of care for conditional TCD velocities is observation. The efficacy of hydroxyurea in preventing conversion from conditional to abnormal TCD (≥200 cm/sec), which confers a higher stroke risk, has not been studied prospectively in a randomized trial. Sparing Conversion to Abnormal TCD Elevation (SCATE #NCT01531387) was a National Heart, Lung, and Blood Institute‐funded Phase III multicenter international clinical trial comparing alternative therapy (hydroxyurea) to standard care (observation) to prevent conversion from conditional to abnormal TCD velocity in children with SCA. SCATE enrolled 38 children from the United States, Jamaica, and Brazil [HbSS (36), HbSβ0‐thalassemia (1), and HbSD (1), median age = 5.4 years (range, 2.7–9.8)]. Because of the slow patient accrual and administrative delays, SCATE was terminated early. In an intention‐to‐treat analysis, the cumulative incidence of abnormal conversion was 9% (95% CI = 0–35%) in the hydroxyurea arm and 47% (95% CI = 6–81%) in observation arm at 15 months (P = 0.16). In post hoc analysis according to treatment received, significantly fewer children on hydroxyurea converted to abnormal TCD velocities when compared with observation (0% vs. 50%, P = 0.02). After a mean of 10.1 months, a significant change in mean TCD velocity was observed with hydroxyurea treatment (−15.5 vs. +10.2 cm/sec, P = 0.02). No stroke events occurred in either arm. Hydroxyurea reduces TCD velocities in children with SCA and conditional velocities. Am. J. Hematol. 90:1099–1105, 2015.

A woman with diabetes presenting with pyomyoma and treated with subtotal hysterectomy: a case report

IntroductionPyomyoma (suppurative leiomyoma of the uterus) is a rare condition resulting from infarction and infection of a leiomyoma. It is more usual in pregnant women or postmenopausal women who have vascular disease. The condition is usually fatal unless treated with appropriate antibiotics and surgical intervention.Case presentationWe report a case of a 44-year-old Afro-Caribbean woman with diabetes who presented with recurrent episodes of abdominal pain and fever over a period of five months. Her problem proved to be a diagnostic dilemma mimicking cholecystitis, pyelonephritis and ovarian cancer. Her blood cultures were positive on one occasion for methicillin-resistant Staphylococcus epidermidis. An ultrasound scan suggested uterine fibroids but a computed tomography scan suggested an ovarian malignancy because the mass appeared heterogeneous with fluid filled areas. She was treated with several courses of antibiotics and eventually at laparotomy, she was found to have a large pyomyoma which was successfully removed by subtotal hysterectomy with immediate and complete resolution of her symptoms.ConclusionThe diagnosis of pyomyoma should be considered in perimenopausal women with large fibroids and pyrexia of unknown origin.

EXpanding Treatment for Existing Neurological Disease (EXTEND): An Open-Label Phase II Clinical Trial of Hydroxyurea Treatment in Sickle Cell Anemia

Background Cerebral vasculopathy in sickle cell anemia (SCA) begins in childhood and features intracranial arterial stenosis with high risk of ischemic stroke. Stroke risk can be reduced by transcranial doppler (TCD) screening and chronic transfusion therapy; however, this approach is impractical in many developing countries. Accumulating evidence supports the use of hydroxyurea for the prevention and treatment of cerebrovascular disease in children with SCA. Recently we reported that hydroxyurea significantly reduced the conversion from conditional TCD velocities to abnormal velocities; whether hydroxyurea can be used for children with newly diagnosed severe cerebrovascular disease in place of starting transfusion therapy remains unknown. Objective The primary objective of the EXpanding Treatment for Existing Neurological Disease (EXTEND) trial is to investigate the effect of open label hydroxyurea on the maximum time-averaged mean velocity (TAMV) after 18 months of treatment compared to the pre-treatment value. Secondary objectives include the effects of hydroxyurea on serial TCD velocities, the incidence of neurological and non-neurological events, quality of life (QOL), body composition and metabolism, toxicity and treatment response, changes to brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA), genetic and serologic markers of disease severity, and cognitive and pulmonary function. Methods This prospective Phase II trial will enroll children with SCA in Jamaica, between the ages of 2 and 17 years, with either conditional (170-199 cm/sec) or abnormal (≥ 200 cm/sec) TCD velocities. Oral hydroxyurea will be administered daily and escalated to the maximum tolerated dose (MTD). Participants will be seen in the Sickle Cell Unit (SCU) in Kingston, Jamaica monthly until achieving MTD, and then every 3 months. TCD will be performed every 6 months. Results Currently, 43 participants have been enrolled out of a projected 50. There was one withdrawal due to immigration, with no permanent screen failures. Of the 43 enrolled, 37 participants have initiated study treatment. Conclusions This trial investigates the effects of hydroxyurea treatment at MTD in children with conditional or abnormal TCD velocities before transfusion therapy and may represent an important advance towards establishing a suitable non-transfusion protocol for stroke prevention in children with SCA. The trial outcomes will have profound significance in developing countries where the disease burden is highest. ClinicalTrial ClinicalTrials.gov NCT02556099; https://clinicaltrials.gov/ct2/show/NCT02556099 (Archived by WebCite at http://www.webcitation.org/6k1yMAa9G)

An infected branchial cyst complicated by retropharyngeal abscess, cervical osteomyelitis and atlanto-axial subluxation

We present a case of a 44-year-old man who visited his general practitioner for recurrent neck swelling, which was found to be a neck abscess. It was aspirated, later recurred, and then surgically excised. Histology was consistent with an infected branchial cyst. Eight months after discharge, the patient presented with a history of progressive neck pain and stiffness and eventually bilateral upper limb weakness. MRI demonstrated a prevertebral abscess complicated by cervical osteomyelitis and atlanto-axial instability. The abscess was drained and appropriate antibiotic treatment was administered. The patient responded well with full recovery of his upper limb strength and resolution of the abscess. However, he had mild persistent neck stiffness.

Subpubic cartilaginous cyst: an unusual cause of a vulval mass

We present a case of a postmenopausal female who visited her doctor for a slowly growing mass in the vulval region. The mass did not show typical clinical features of a vulval neoplasm. Magnetic resonance imaging (MRI) revealed a mass arising from the undersurface of the symphysis pubis. A literature review revealed characteristics of this lesion compatible with a subpubic cartilaginous cyst—a rare benign degenerative condition of the symphysis pubis. As a result the mass was managed non-operatively and the patient remains well 2 years later. This article highlights the role of MRI in the diagnosis of this unusual vulval mass.

Pituitary Apoplexy Associated with Ptosis

Pituitary tumours are the most common sellar masses, frequently presenting with visual impairment and endocrine abnormalities. Two cases of pituitary tumour presenting with ptosis are reported.

Moyamoya syndrome in sickle cell anaemia: a cause of recurrent stroke

Summary We report a case with interesting imaging findings as well as an unfortunate but not unexpected clinical outcome. Our patient, an 8-year-old Jamaican boy of Afro-Caribbean descent with homozygous sickle cell disease, presented with left-sided upper limb weakness. He had a history of recurrent cerebrovascular accidents and transient ischaemic attacks beginning at 4 years of age. MRI revealed old bilateral infarctions and the ivy sign on fluid-attenuated inversion recovery sequences. MR angiography demonstrated numerous collaterals, most apparently arising from the left internal carotid, consistent with moyamoya syndrome. The patient had a full recovery and remained well for almost 2 years when he suffered another stroke.

Transcranial Doppler velocity among Jamaican children with sickle cell anaemia: determining the significance of haematological values and nutrition

This study investigated the association of nutritional and haematological variables with maximum time‐averaged mean velocity (TAMV) measured by transcranial Doppler (TCD) velocity and the agreement of classification between two protocols. TCD categories included: normal (<170 cm/s), conditional (170–199 cm/s) and abnormal (≥200 cm/s) based on TAMV in distal internal carotid artery (dICA), middle cerebral artery (MCA), internal carotid bifurcation, anterior and posterior cerebral arteries. Of 358 children with sickle cell anaemia (SCA) examined, the mean age (±standard deviation) was 7·4 ± 2·7 years; 13·1% and 6·7% had conditional and abnormal velocities, respectively. Children with abnormal TCD velocities had higher prevalence of prior stroke (P = 0·006). Increased TAMV was associated with younger age (P = 0·001), lower weight (P = 0·001), height (P = 0·007) and oxygen saturation (P = 0·005). There was no association of TAMV with height‐age or body mass index (BMI) z‐scores. Adjusting for gender, BMI z‐score, age, previous stroke and oxygen saturation, mean corpuscular volume (P = 0·005) and reticulocyte count (P = 0·013) were positively associated with TAMV, while haemoglobin concentration (P = 0·009) was negatively associated. There was good agreement [99%; weighted Kappa 0·98 (95% confidence interval 0·89–1), P = 0·0001] in TCD classification using data from five vessels versus two vessels (dICA and MCA). Haematological variables, rather than nutritional status, may be useful markers that identify high‐risk children with SCA.