NUTRITIONAL STATUS AND RISK FACTORS ASSOCIATED WITH SEVERE ACUTE MALNUTRITION AMONG HIV-INFECTED CHILDREN ENROLLED IN THE PAEDIATRIC HIV CLINIC, KORLE BU TEACHING HOSPITAL, ACCRA, GHANA.

Background: Malnutrition remains a common problem among Human Immunodeficiency Virus (HIV)-infected children even while receiving antiretroviral therapy leading to disease progression and reduced survival. Aim: To assess the nutritional status and risk factors associated with severe acute malnutrition (SAM) among HIV-infected children aged 1 to 15 years attending the Paediatric HIV Clinic at Korle Bu Teaching Hospital (KBTH), Accra. Methods: A cross-sectional study was conducted from October 2018 to January 2019 at the Clinic during which 150 participants aged 15 to 179 months were systematically recruited. A structured interview, physical examination, including anthropometric measurements, data extraction from hospital records, and laboratory investigations were conducted. Weight-for- age, weight-for-length/height, length/height-for-age, body mass index Z scores, and mid-upper arm circumference-for-age were obtained. Logistic regression models were used to assess the crude and adjusted odds of the nutritional status on the socio-demographic, clinical, and HIV-related characteristics of the participants at alpha= 0.05. Results: The prevalence of SAM, moderate acute malnutrition and normal nutrition were 4.0% (6/149), 13.4% (20/149) and 80.5% (120/149), respectively, whilst 1.3% (2/149) were overweight and 0.7% (1/149) obese. Stunting and severe stunting were 18.1% (27/149) and 6.7% (10/149) prevalent, respectively. SAM was significantly associated with oral thrush among participants in the adjusted model. The prevalence of mild-, moderate- and severe-anaemia were 23.7% (33/139), 38.8% (54/139) and 1.4% (2/139), respectively. Conclusion: Malnutrition is prevalent among HIV-infected children on antiretroviral therapy at KBTH. SAM is associated with oral thrush.

Metastatic Death Based on Presenting Features and Treatment for Advanced Intraocular Retinoblastoma: A Multicenter Registry-Based Study.

PURPOSE: To evaluate presenting features, tumor size, and treatment methods for risk of metastatic death due to advanced intraocular retinoblastoma (RB). DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: A total of 1841 patients with advanced RB. METHODS: Advanced RB was defined by 8th edition American Joint Committee on Cancer (AJCC) categories cT2 and cT3 and new AJCC-Ophthalmic Oncology Task Force (OOTF) Size Groups (1: < 50% of globe volume, 2: > 50% but < 2/3, 3: > 2/3, and 4: diffuse infiltrating RB). Treatments were primary enucleation, systemic chemotherapy with secondary enucleation, and systemic chemotherapy with eye salvage. MAIN OUTCOME MEASURES: Metastatic death. RESULTS: The 5-year Kaplan-Meier cumulative survival estimates by patient-level AJCC clinical subcategories were 98% for cT2a, 96% for cT2b, 88% for cT3a, 95% for cT3b, 92% for cT3c, 84% for cT3d, and 75% for cT3e RB. Survival estimates by treatment modality were 96% for primary enucleation, 89% for systemic chemotherapy and secondary enucleation, and 90% for systemic chemotherapy with eye salvage. Risk of metastatic mortality increased with increasing cT subcategory (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of metastatic mortality in categories cT3c (glaucoma, hazard ratio [HR], 4.9; P = 0.011), cT3d (intraocular hemorrhage, HR, 14.0; P < 0.001), and cT3e (orbital cellulitis, HR, 19.6; P < 0.001) than in category cT2a and with systemic chemotherapy with secondary enucleation (HR, 3.3; P < 0.001) and eye salvage (HR, 4.9; P < 0.001) than with primary enucleation. The 5-year Kaplan-Meier cumulative survival estimates by AJCC-OOTF Size Groups 1 to 4 were 99%, 96%, 94%, and 83%, respectively. Mortality from metastatic RB increased with increasing Size Group (P < 0.001). Cox proportional hazards regression analysis revealed that patients with Size Group 3 (HR, 10.0; P = 0.002) and 4 (HR, 41.1; P < 0.001) had a greater risk of metastatic mortality than Size Group 1. CONCLUSIONS: The AJCC-RB cT2 and cT3 subcategories and size-based AJCC-OOTF Groups 3 (> 2/3 globe volume) and 4 (diffuse infiltrating RB) provided a robust stratification of clinical risk for metastatic death in advanced intraocular RB. Primary enucleation offered the highest survival rates for patients with advanced intraocular RB.

High-risk Pathologic Features Based on Presenting Findings in Advanced Intraocular Retinoblastoma: A Multicenter, International Data-Sharing American Joint Committee on Cancer Study.

PURPOSE: To determine the value of clinical features for advanced intraocular retinoblastoma as defined by the eighth edition of the American Joint Committee on Cancer (AJCC) cT3 category and AJCC Ophthalmic Oncology Task Force (OOTF) Size Groups to predict the high-risk pathologic features. DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: Eighteen ophthalmic oncology centers from 13 countries over 6 continents shared evaluations of 942 eyes enucleated as primary treatment for AJCC cT3 and, for comparison, cT2 retinoblastoma. METHODS: International, multicenter, registry-based data were pooled from patients enrolled between 2001 and 2013. High-risk pathologic features were defined as AJCC categories pT3 and pT4. In addition, AJCC OOTF Size Groups were defined as follows: (1) less than half, (2) more than half but less than two thirds, (3) more than two thirds of globe volume involved, and (4) diffuse infiltrating retinoblastoma. MAIN OUTCOME MEASURES: Statistical risk of high-risk pathologic features corresponding to AJCC cT3 subcategories and AJCC OOTF Size Groups. RESULTS: Of 942 retinoblastoma eyes treated by primary enucleation, 282 (30%) showed high-risk pathologic features. Both cT subcategories and AJCC OOTF Size Groups (P < 0.001 for both) were associated with high-risk pathologic features. On logistic regression analysis, cT3c (iris neovascularization with glaucoma), cT3d (intraocular hemorrhage), and cT3e (aseptic orbital cellulitis) were predictive factors for high-risk pathologic features when compared with cT2a with an odds ratio of 2.3 (P = 0.002), 2.5 (P = 0.002), and 3.3 (P = 0.019), respectively. Size Group 3 (more than two-thirds globe volume) and 4 (diffuse infiltrative retinoblastoma) were the best predictive factors with an odds ratio of 3.3 and 4.1 (P < 0.001 for both), respectively, for high-risk pathologic features when compared with Size Groups 1 (i.e., < 50% of globe volume). CONCLUSIONS: The AJCC retinoblastoma staging clinical cT3c-e subcategories (glaucoma, intraocular hemorrhage, and aseptic orbital cellulitis, respectively) as well as the AJCC OOTF Size Groups 3 (tumor more than two thirds of globe volume) and 4 (diffuse infiltrative retinoblastoma) both allowed stratification of clinical risk factors that can be used to predict the presence of high-risk pathologic features and thus facilitate treatment decisions.

Global Retinoblastoma Treatment Outcomes: Association with National Income Level.

PURPOSE: To compare metastasis-related mortality, local treatment failure, and globe salvage after retinoblastoma in countries with different national income levels. DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: Two thousand one hundred ninety patients, 18 ophthalmic oncology centers, and 13 countries on 6 continents. METHODS: Multicenter registry-based data were pooled from retinoblastoma patients enrolled between January 2001 and December 2013. Adequate data to allow American Joint Committee on Cancer staging, eighth edition, and analysis for the main outcome measures were available for 2085 patients. Each country was classified by national income level, as defined by the 2017 United Nations World Population Prospects, and included high-income countries (HICs), upper middle-income countries (UMICs), and lower middle-income countries (LMICs). Patient survival was estimated with the Kaplan-Meier method. Logistic and Cox proportional hazards regression models were used to determine associations between national income and treatment outcomes. MAIN OUTCOME MEASURES: Metastasis-related mortality and local treatment failure (defined as use of secondary enucleation or external beam radiation therapy). RESULTS: Most (60%) study patients resided in UMICs and LMICs. The global median age at diagnosis was 17.0 months and higher in UMICs (20.0 months) and LMICs (20.0 months) than HICs (14.0 months; P < 0.001). Patients in UMICs and LMICs reported higher rates of disease-specific metastasis-related mortality and local treatment failure. As compared with HICs, metastasis-related mortality was 10.3-fold higher for UMICs and 9.3-fold higher for LMICs, and the risk for local treatment failure was 2.2-fold and 1.6-fold higher, respectively (all P < 0.001). CONCLUSIONS: This international, multicenter, registry-based analysis of retinoblastoma management revealed that lower national income levels were associated with significantly higher rates of metastasis-related mortality, local treatment failure, and lower globe salvage.

A Multicenter, International Collaborative Study for American Joint Committee on Cancer Staging of Retinoblastoma: Part I: Metastasis-Associated Mortality.

PURPOSE: To evaluate the ability of the 8th edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual to estimate metastatic and mortality rates for children with retinoblastoma (RB). DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: A total of 2190 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents. METHODS: Patient-specific data fields for RB were designed and selected by subcommittee. All patients with RB with adequate records to allow tumor staging by the AJCC criteria and follow-up for metastatic disease were studied. MAIN OUTCOME MEASURES: Metastasis-related 5- and 10-year survival data after initial tumor staging were estimated with the Kaplan-Meier method depending on AJCC clinical (cTNM) and pathological (pTNM) tumor, node, metastasis category and age, tumor laterality, and presence of heritable trait. RESULTS: Of 2190 patients, the records of 2085 patients (95.2%) with 2905 eyes were complete. The median age at diagnosis was 17.0 months. A total of 1260 patients (65.4%) had unilateral RB. Among the 2085 patients, tumor categories were cT1a in 55 (2.6%), cT1b in 168 (8.1%), cT2a in 197 (9.4%), cT2b in 812 (38.9%), cT3 in 835 (40.0%), and cT4 in 18 (0.9%). Of these, 1397 eyes in 1353 patients (48.1%) were treated with enucleation. A total of 109 patients (5.2%) developed metastases and died. The median time (n = 92) from diagnosis to metastasis was 9.50 months. The 5-year Kaplan-Meier cumulative survival estimates by clinical tumor categories were 100% for category cT1a, 98% (95% confidence interval [CI], 97-99) for cT1b and cT2a, 96% (95% CI, 95-97) for cT2b, 89% (95% CI, 88-90) for cT3 tumors, and 45% (95% CI, 31-59) for cT4 tumors. Risk of metastasis increased with increasing cT (and pT) category (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of metastasis in category cT3 (hazard rate [HR], 8.09; 95% CI, 2.55-25.70; P < 0.001) and cT4 (HR, 48.55; 95% CI, 12.86-183.27; P < 0.001) compared with category cT1. Age, tumor laterality, and presence of heritable traits did not influence the incidence of metastatic disease. CONCLUSIONS: Multicenter, international, internet-based data sharing facilitated analysis of the 8th edition AJCC RB Staging System for metastasis-related mortality and offered a proof of concept yielding quantitative, predictive estimates per category in a large, real-life, heterogeneous patient population with RB.

A Multicenter, International Collaborative Study for American Joint Committee on Cancer Staging of Retinoblastoma: Part II: Treatment Success and Globe Salvage.

PURPOSE: To evaluate the ability of the American Joint Committee on Cancer (AJCC) 8th edition to predict local tumor control and globe salvage for children with retinoblastoma (RB). DESIGN: International, multicenter, registry-based retrospective case series. PARTICIPANTS: A total of 2854 eyes of 2097 patients from 18 ophthalmic oncology centers from 13 countries over 6 continents. METHODS: International, multicenter, registry-based data were pooled from patients enrolled between January 2001 and December 2013. All RB eyes with adequate records to allow tumor staging by the AJCC 8th edition criteria and follow-up to ascertain treatment outcomes were included. MAIN OUTCOME MEASURES: Globe-salvage rates were estimated by AJCC clinical (cTNMH) categories and tumor laterality. Local treatment failure was defined as use of enucleation or external beam radiation therapy (EBRT), with or without plaque brachytherapy or intra-arterial chemotherapy (IAC). RESULTS: Unilateral RB occurred in 1340 eyes (47%). Among the 2854 eyes, tumor categories were cT1 to cT4 in 696 eyes (24%), 1334 eyes (47%), 802 eyes (28%), and 22 eyes (1%), respectively. Of these, 1275 eyes (45%) were salvaged, and 1179 eyes (41%) and 400 eyes (14%) underwent primary and secondary enucleation, respectively. The 2- and 5-year Kaplan-Meier cumulative globe-salvage rates without the use of EBRT by cTNMH categories were 97% and 96% for category cT1a tumors, 94% and 88% for cT1b tumors, 68% and 60% for cT2a tumors, 66% and 57% for cT2b tumors, and 32% and 25% for cT3 tumors, respectively. Risk of local treatment failure increased with increasing cT category (P < 0.001). Cox proportional hazards regression analysis confirmed a higher risk of local treatment failure in categories cT1b (hazard ratio [HR], 3.5; P = 0.004), cT2a (HR, 15.1; P < 0.001), cT2b (HR, 16.4; P < 0.001), and cT3 (HR, 45.0; P < 0.001) compared with category cT1a. Use of plaque brachytherapy and IAC improved local tumor control in categories cT1a (P = 0.031) and cT1b (P < 0.001). CONCLUSIONS: Multicenter, international, internet-based data sharing validated the 8th edition AJCC RB staging to predict globe-salvage in a large, heterogeneous, real-world patient population with RB.

The changing clinical pattern of endemic Burkitt lymphoma in Western Africa: Experience from a tertiary center in Ghana.

BACKGROUND: Burkitt lymphoma (BL) is the most common childhood cancer in Ghana, where the endemic variant is the predominant subtype and historically presents as a highly chemo-sensitive jaw tumor. This study aimed to update the current epidemiological characteristics of childhood BL in our institution. PROCEDURE: Patient data for all children diagnosed with BL and seen at Korle Bu Teaching Hospital between January 2007 and December 2012 were retrospectively analyzed. RESULTS: BL was diagnosed in 173 children (<13 years) during the study period, with the abdomen as the most common tumor site (46%) followed by the jaw (31%). Abdominal tumors were associated with advanced/disseminated disease (P = 0.002), and were more likely to occur in females irrespective of tumor stage (relative risk = 1.56 [95% CI; 1.1-12.3]). Twenty-five percent (43/173) of the study cohort died and mortality was influenced by increasing age (P = 0.02) and advanced disease (P = 0.03). Treatment delay was experienced by nine in ten patients primarily due to familial financial constraint (75%). Treatment abandonment was observed as a first event in 94% of patients and two thirds of children in the study were eventually lost to follow-up. CONCLUSION: The predominance of primary abdominal tumors in our study cohort may indicate a changing epidemiological pattern of BL in Ghana. High rates of treatment delay and abandonment were evident and are likely to be contributing factors to the poor childhood cancer survival outcomes seen in resource-limited countries in Africa.

Short-term chemotherapy-related complications and undernutrition in children diagnosed with cancer at Korle Bu Teaching Hospital, Accra, Ghana: A prospective cohort study.

Undernutrition in children with cancer is associated with complications during cancer therapy. The study objective was to determine the association between specific anthropometric parameters and short-term chemotherapy-related complications and mortality. This was a hospital-based, prospective cohort study of children, age ≤12 years, with a new cancer diagnosis at the Paediatric Oncology Unit, Korle Bu Teaching Hospital, Ghana. Socio-demographic information, cancer characteristics and anthropometric measurements were obtained at enrolment. Participants were followed up for twelve weeks from commencement of chemotherapy and selected treatment-related complications such as anaemia and thrombocytopenia requiring transfusions, prolonged neutropenia resulting in treatment delays, febrile neutropenia, mucositis and death were recorded. A total of 133 participants were recruited with a median age of 4.5 years. Eighty-one (60.9%) were diagnosed with solid tumours, 31 (23.3%) had leukaemias and 21 (15.8%) had lymphomas. Of the anthropometric parameters assessed, only arm anthropometry using upper arm muscle area (UAMA) and mid-upper arm circumference (MUAC) were associated with complications. Participants with wasting were more likely to develop anaemia and mucositis. However, the incidence of prolonged neutropenia was significantly higher among participants with average UAMA (p = 0.043) and low average UAMA (p = 0.049) compared to those with low UAMA. Risk of neutropenia was also significantly less among those with wasting by MUAC compared to those well-nourished (p = 0.045). Twenty-three participants (17.3%) died with a greater proportion (11/44; 25%) occurring in those who were wasted using MUAC. These findings underscore the need for nutritional surveillance at diagnosis and during chemotherapy, particularly where co-morbid disease is prevalent.

Current Realities of Wilms Tumor Burden and Therapy in Ghana.

BACKGROUND: Between 2005 and 2014, Ghana's Wilms tumor (WT) 2-year disease-free survival of 44% trailed behind that of high-income countries. This study aimed to uncover social determinants of health leading to preventable WT death in Ghana. METHODS: WT patient records (2014-2022) at Korle-Bu Teaching Hospital (KBTH; Ghana) were reviewed retrospectively. Demographics, clinical course, tumor characteristics, and survival were evaluated using t-tests, Pearson Chi-square, and multivariate Cox logistic regression. RESULTS: Of 127 patients identified, 65 were female. Median age was 44 months [IQR 25-66]. Forty-eight patients (38%) presented with distant metastasis (75% lung, 25% liver), which associated with hypoalbuminemia (p = 0.009), caregiver informal employment (p = 0.04), and larger tumors (p = 0.002). Despite neoadjuvant chemotherapy shrinking 84% of tumors, larger initial size associated with incomplete resection (p = 0.046). Of 110 nephrectomies, 31 patients had residual disease, negatively impacting survival (p = 2.7 × 10-5). Twenty-two patients (17%) abandoned treatment (45% before nephrectomy; 55% after nephrectomy), with seven patients ultimately lost to follow-up (LTFU). Decedents represented 43% of stage IV patients compared to 28% in other stages. Event-free survival (EFS) was 60% at 4 years with overall survival (OS) at 67%. CONCLUSIONS: Although Ghana's WT survival has improved, informal employment and distance from KBTH predisposed patients to delayed referral, greater tumor burden, hypoalbuminemia, and lower survival. TYPE OF STUDY: Prognosis Study. LEVEL OF EVIDENCE: II.

Retinoblastoma seeds: impact on American Joint Committee on Cancer clinical staging.

AIM: To investigate whether the American Joint Committee on Cancer (AJCC) clinical category cT2b needs to be subclassified by the type and distribution of retinoblastoma (RB) seeding. METHODS: Multicentre, international registry-based data were collected from RB centres enrolled between January 2001 and December 2013. 1054 RB eyes with vitreous or subretinal seeds from 18 ophthalmic oncology centres, in 13 countries within six continents were analysed. Local treatment failure was defined as the use of secondary enucleation or external beam radiation therapy (EBRT) and was estimated with the Kaplan-Meier method. RESULTS: Clinical category cT2b included 1054 eyes. Median age at presentation was 16.0 months. Of these, 428 (40.6%) eyes were salvaged, and 430 (40.8%) were treated with primary and 196 (18.6%) with secondary enucleation. Of the 592 eyes that had complete data for globe salvage analysis, the distribution of seeds was focal in 143 (24.2%) and diffuse in 449 (75.8%). The 5-year Kaplan-Meier cumulative globe-salvage (without EBRT) was 78% and 49% for eyes with focal and diffuse RB seeding, respectively. Cox proportional hazards regression analysis confirmed a higher local treatment failure risk with diffuse seeds as compared with focal seeds (hazard rate: 2.8; p<0.001). There was insufficient evidence to prove or disprove an association between vitreous seed type and local treatment failure risk(p=0.06). CONCLUSION: This international, multicentre, registry-based analysis of RB eyes affirmed that eyes with diffuse intraocular distribution of RB seeds at diagnosis had a higher risk of local treatment failure when compared with focal seeds. Subclassification of AJCC RB category cT2b into focal vs diffuse seeds will improve prognostication for eye salvage.

The pattern of neonatal admissions and mortality at a regional and district hospital in the Upper West Region of Ghana; a cross sectional study.

BACKGROUND: High global neonatal deaths have triggered efforts to improve facility-based care. However, the outcomes achievable at different levels of care are unclear. This study compared morbidity and mortality patterns of newborns admitted to a regional and a district hospital in Ghana to determine outcome, risk and modifiable factors associated with mortality. OBJECTIVE: This study compared morbidity and mortality patterns of newborns admitted to a regional and a district hospital in Ghana to determine outcome, risk and modifiable factors associated with mortality. METHODS: A cross-sectional study involving a records-review over one year at the Upper West Regional Hospital, and three years at St Joseph's District Hospital, Jirapa was carried out. Age, sex, gestational age, weight, duration of admission, diagnosis, among others were examined. The data were analysed and statistical inference made. RESULTS: Altogether, 2004 newborns were examined, comprising 1,241(62%) from St Joseph's District Hospital and 763(38%) from Upper West Regional Hospital. The proportion of neonatal deaths was similar, 8.94% (St Joseph's District Hospital) and 8.91% (Upper West Regional Hospital). Prematurity, neonatal sepsis, birth asphyxia, low birth weight, neonatal jaundice and pneumonia contributed the most to mortality and suspected infections including malaria accounted for almost half (45.5%). Mortality was significantly associated with duration of stay of 48 hours, being premature, and being younger than 3 days. CONCLUSION: Majority of the mortality among the neonates admitted was due to preventable causes. Better stabilization and further studies on the epidemiology of sepsis, prematurity, low birth weight, including the contribution of malaria to these and outcome of transferred neonates are needed.

Anaemia and zidovudine-containing antiretroviral therapy in paediatric antiretroviral programmes in the IeDEA Paediatric West African Database to evaluate AIDS.

INTRODUCTION: There is a risk of anaemia among HIV-infected children on antiretroviral therapy (ART) containing zidovudine (ZDV) recommended in first-line regimens in the WHO guidelines. We estimated the risk of severe anaemia after initiation of a ZDV-containing regimen in HIV-infected children included in the IeDEA West African database. METHODS: Standardized collection of data from HIV-infected children (positive PCR<18 months or positive serology ≥ 18 months) followed up in HIV programmes was included in the regional IeDEA West Africa collaboration. Ten clinical centres from seven countries contributed (Benin, Burkina Faso, Côte d'Ivoire, Gambia, Ghana, Mali and Senegal) to this collection. Inclusion criteria were age <16 years and starting ART. We explored the data quality of haemoglobin documentation over time and the incidence and predictors of severe anaemia (Hb<7 g/dL) per 100 child-years of follow-up over the duration of first-line antiretroviral therapy. RESULTS: As of December 2009, among the 2933 children included in the collaboration, 45% were girls, median age was five years; median CD4 cell percentage was 13%; median weight-for-age z-score was-2.7; and 1772 (60.4%) had a first-line ZDV-containing regimen. At baseline, 70% of the children with a first-line ZDV-containing regimen had a haemoglobin measure available versus 76% in those not on ZDV (p ≤ 0.01): the prevalence of severe anaemia was 3.0% (n=38) in the ZDV group versus 10.2% (n=89) in those without (p<0. 01). Over the first-line follow-up, 58.9% of the children had ≥ 1 measure of haemoglobin available in those exposed to ZDV versus 60.4% of those not (p=0.45). Severe anaemia occurred in 92 children with an incidence of 2.47 per 100 child-years of follow-up in those on a ZDV-containing regimen versus 4.25 in those not (p ≤ 0.01). Adjusted for age at ART initiation and first-line regimen, a weight-for-age z-score ≤-3 was a strong predictor associated with a 5.59 times risk of severe anaemia (p<0.01). CONCLUSIONS: Severe anaemia is frequent at baseline and guides the first-line ART prescription, but its incidence seems rare among children on ART. Severe malnutrition at baseline is a strong predictor for development of severe anaemia, and interventions to address this should form an integral component of clinical care.