Hydroxyurea Therapy for Neurological and Cognitive Protection in Pediatric Sickle Cell Anemia in Uganda (BRAIN SAFE II): Protocol for a single-arm open label trial.

Background: Children with sickle cell anemia (SCA) in Sub-Saharan Africa are at high risk of sickle cerebrovascular injury (SCVI). Hydroxyurea, a commonly used disease-modifying therapy, may prevent or decrease SCVI for reduced incident stroke, stroke risk and potentially cognitive dysfunction. We aim to test the impact of daily hydroxyurea therapy on these outcomes in Ugandan children with SCA. We hypothesize that hydroxyurea therapy over 36 months will prevent, stabilize or improve these complications of SCA. Methods: The BRAIN SAFE II study is an open-label, single-arm trial of daily hydroxyurea for 270 children with SCA (HbSS) in Uganda, ages 3-9 years. Following baseline assessments, participants began hydroxyurea therapy and clinically followed per local guidelines. Standard hydroxyurea dose is escalated to maximum tolerated dose (MTD). SCVI is assessed by cerebral arterial velocity using Doppler ultrasound, with cognitive function determined by formal neurocognitive testing (primary outcomes). Structural SCVI is assessed by magnetic resonance imaging (MRI) and angiography (MRA) in a sub-sample of 90 participants ages ≥5 years, along with biomarkers of anemia, inflammation and malnutrition (secondary outcomes). At trial midpoint (18 months) and completion (36 months), primary outcomes will be compared to participants' baseline to determine hydroxyurea impact and relationships to secondary outcomes. Conclusion: This open-label, single-arm trial will examine the impact of hydroxyurea on preventing or ameliorating SCA SCVI in children, assessed by reducing incident stroke, stroke risk and neurocognitive dysfunction. Trial results will provide important insight into the role of hydroxyurea therapy on critical manifestations of SCVI in children with SCA.

Synchronous bilateral Wilms' tumor with liver metastasis.

BACKGROUND: Wilms' tumor (nephroblastoma) is mostly unilateral; however, bilateral Wilms' tumors are seen in about 5-8% of patients. This can be synchronous or metachronous. It is uncommon to get liver metastasis from bilateral Wilms' tumor. CASE PRESENTATION: An 8-year-old male Ugandan presented with a history of abdominal swelling and flank pains for 1 year. There was no history of hematuria. Both ultrasound and computed tomography of the abdomen demonstrated multiple solid lesions in both kidneys and a huge solid mass in segments V, VI, VII and VIII of the liver. Histological examination of renal biopsy specimen was favorable for chemotherapeutic regimens. However, following a multidisciplinary tumor board consensus, a nephron-sparing surgery was deemed unsuitable, and he was managed conservatively with chemotherapy (adriamycin and vincristine) with a palliative intent. CONCLUSIONS: Metastatic bilateral Wilms' tumor has a particularly poor prognosis. There are no clear evidence-based guidelines for the management of this rare presentation. This patient benefited from early palliative care and symptom management.

T-cell non-Hodgkin's lymphoma of both breasts: An uncommon presentation of a common disease.

Secondary T-cell non-Hodgkin's lymphoma of the breasts is a very rare disease and can be easily missed as inflammatory carcinoma at initial presentation. High index of suspicion and radiological investigations has a big role in identifying the primary lymphoma.