Nigerian Cohort Research Articles

Attributes of Pathological Fractures in a Nigerian myeloma cohort

Multiple Myeloma (MM) is a plasma cell tumor usually characterized by lytic bone lesions. Pathological Fracture (PF) is a debilitating condition that usually affects a patient’s psychomotor functions, treatment modality, morbidity, and outcome. We evaluated the associations, characteristics, and impact of PF on survival in a group of Nigerian myeloma cohort. A 10-year (2011-2021) retrospective review of MM data from Nigerian tertiary hospital haemato-oncology unit to evaluate attributes of PFs in myeloma cohort. Sixty-six patients had MM of which 23 had PF while forty-three had no fractures. Of the number with PF, 18 had lytic bone lesions, while 20 had bone pains. Monoclonal Immunoglobulin G was predominant followed by Immunoglobulin A. Significant correlations existed between hemoglobin level (r=0.446, p=0.002); platelet count (r=-0.347, p=0.041), serum calcium (r=0.471, p=0.006) and bone pains; as well as between urea level (r=-0.787, p=001), creatinine level (r=-0.853, p=0.001) and renal impairment respectively. PFs are associated with diabetes, peptic ulcer disease, hypertension, nephropathy, and arthritis. Bortezomib-based regimen was the choice treatment. Overall survival was 16 (69.6%) with 7 (30.4%) mortality. PF is common amongst the myeloma cohort with the spine being the most common site. It is associated with significant comorbidities like hypertension, diabetes, peptic ulcer disease, and paraplegia and is characterized by severe debilitating bone pains, anemia, hypercalcemia, raised plasma monoclonal immunoglobulin, renal impairment, loss of man-hour at work, and psychosocial imbalance. The impact of the fracture has increased morbidity and mortality and has reduced the median survival duration to as low as 4 years.

Atypical Variants of Spinal Dysraphism: A Case Series

Abstract The aim of this study is to present and discuss atypical instances of spina bifida (SB) within a Nigerian paediatric cohort, highlighting their distinctive clinicoradiological features. Additionally, a brief literature review is provided to contextualise these congenital anomalies. This series comprises eight rare cases of SB managed in a Nigerian neurosurgical facility. Additionally, a brief literature review is provided to contextualise these congenital anomalies. This case series comprises eight rare cases of SB managed in a Nigerian neurosurgical facility. Amongst these, four cases exhibited segmental spinal dysgenesis (SSD; one thoracolumbar, one lumbar, and two sacral). Each of these cases demonstrated diverse associated musculoskeletal, cutaneous, and perineal anomalies, accompanied by varying degrees of neurological dysfunction. Other cases included lipomyelomeningocele (LMMC), human tail (HT), membranous meningocele, and myeloschisis (MSS). Autonomic dysfunction was a common feature in all of the cases, whilst two of the patients presented with congenital kyphotic spinal deformity. Lower limb anomalies varied, including congenital talipes equinovarus deformity, pes planus, congenital calcaneovagus deformity, rocker bottom feet, clinodactyly, and tetrapolydactyly. Remarkably, none of the patients exhibited clinical features indicative of hydrocephalus. SSD, LMMC, HT, membranous meningocele, and MSS represent atypical forms of SB in the Nigerian paediatric population. Early neuroimaging of patients with suspected spinal dysraphism is crucial, as it may reveal a spectrum of diverse vertebral anomalies associated with this neurological condition within the African population.

Quantified retrospective biomonitoring of fetal and infant elemental exposure using LA-ICP-MS analysis of deciduous dentin in three contrasting human cohorts.

Spatial elemental analysis of deciduous tooth dentin combined with odontochronological estimates can provide an early life (in utero to ~2 years of age) history of inorganic element exposure and status. To demonstrate the importance of data normalization to a certified reference material to enable between-study comparisons, using populations with assumed contrasting elemental exposures. We used laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) of dentin to derive a history of elemental composition from three distinct cohort studies: a present day rural cohort, (the New Hampshire Birth Cohort Study (NHBCS; N = 154)), an historical cohort from an urban area (1958-1970), (the St. Louis Baby Tooth Study (SLBT; N = 78)), and a present-day Nigerian cohort established to study maternal HIV transmission (Dental caries and its association with Oral Microbiomes and HIV in young children-Nigeria (DOMHaIN; N = 31)). We report Li, Al, Mn, Cu, Zn, Sr, Ba and Pb concentrations (µg/g) and qualitatively examine As, Cd and Hg across all three cohorts. Rates of detection were highest, both overall and for each cohort individually, for Zn, Sr, Ba and Li. Zinc was detected in 100% of samples and was stably present in teeth at a concentration range of 64 - 86 µg/g. Mercury, As and Cd detection rates were the lowest, and had high variability within individual ablated spots. We found the highest concentrations of Pb in the pre- and postnatal dentin of the SLBT cohort, consistent with the prevalent use of Pb as an additive to gasoline prior to 1975. The characteristic decline in Mn after the second trimester was observed in all cohorts. Spatially resolved elemental analysis of deciduous teeth combined with methods for estimating crown formation times can be used to reconstruct an early-life history of elemental exposure inaccessible via other biomarkers. Quantification of data into absolute values using an external standard reference material has not been conducted since 2012, preventing comparison between studies, a common and highly informative component of epidemiology. We demonstrate, with three contrasting populations, that absolute quantification produces data with the lowest variability, compares well with available data and recommends that future tooth biomarker studies report data in this way.

Genome-wide association study identifies human genetic variants associated with fatal outcome from Lassa fever

Infection with Lassa virus (LASV) can cause Lassa fever, a haemorrhagic illness with an estimated fatality rate of 29.7%, but causes no or mild symptoms in many individuals. Here, to investigate whether human genetic variation underlies the heterogeneity of LASV infection, we carried out genome-wide association studies (GWAS) as well as seroprevalence surveys, human leukocyte antigen typing and high-throughput variant functional characterization assays. We analysed Lassa fever susceptibility and fatal outcomes in 533 cases of Lassa fever and 1,986 population controls recruited over a 7 year period in Nigeria and Sierra Leone. We detected genome-wide significant variant associations with Lassa fever fatal outcomes near GRM7 and LIF in the Nigerian cohort. We also show that a haplotype bearing signatures of positive selection and overlapping LARGE1, a required LASV entry factor, is associated with decreased risk of Lassa fever in the Nigerian cohort but not in the Sierra Leone cohort. Overall, we identified variants and genes that may impact the risk of severe Lassa fever, demonstrating how GWAS can provide insight into viral pathogenesis.

Outcomes of a social media campaign to promote COVID-19 vaccination in Nigeria.

The COVID-19 pandemic has been an historic challenge to public health and behavior change programs. In low -and middle-income countries (LMICs) such as Nigeria, there have been challenges in promoting vaccination. Vaccine hesitancy and social norms related to vaccination may be important factors in promoting or inhibiting not only COVID vaccination, but other routine vaccinations as well. The aim of this study was to conduct a national-level quasi-experimental evaluation of a social media based COVID-19 vaccination promotion campaign in Nigeria run in 2022. We followed a longitudinal cohort of Nigerians (at baseline) drawn from all 37 states in Nigeria over a 10-month period. This was done at 3 time points to evaluate psychosocial predictors of vaccination and vaccination outcomes following a theory of change based on Diffusion of Innovations, Social Norms Theory, and the Motivation, Opportunity, Ability (MOA) Framework. In a quasi-experimental design, participants in 6 Nigerian states where the social media campaign was run (treatment) were compared to participants from non-treatment states. This study highlights new social media-based data collection techniques. The study found that vaccination rates increased in treatment states compared to non-treatment states, and that these effects were strongest between baseline and first follow up (December 2021 to March 2022). We also found that more pro-vaccination social norms at one time point are associated with higher vaccination rates at a later time point. Social media campaigns are a promising approach to increasing vaccination at scale in LMICs, and social norms are an important factor in promoting vaccination, which is consistent with the Social Norms Theory. We describe implications for future vaccination campaigns and identify future research priorities in this area.

Pathologic Complete Response Following Neoadjuvant Chemotherapy for Breast Cancer in a Nigerian Cohort

Background: Pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) is a marker for important clinical outcomes in the management of breast cancer. In Nigeria where the majority of patients are candidates for NAC, there is limited data on pCR following NAC. This study evaluated the pCR rate in a cohort of Nigerian patients. Methods: A retrospective review of patients who had NAC and mastectomy for breast cancer between 2017 and 2022. Relevant baseline clinicopathological and treatment data were obtained, pCR was defined as the absence of invasive cancer with or without in situ disease in the breast. The relationship between receptor status, type of chemotherapy and pCR was evaluated. Results: One hundred and sixty six of the 250 patients who had mastectomy during the period had NAC and were eligible for analysis. The mean age was 50.1±11.1, the majority had stage 3 disease. Overall (pCR) rate was 19.9% with the latter part of the study corresponding to the period with increased use of taxanes, having higher pCR (35.9% in 2022 vs 7.4% in 2017, p=0.024). Patients with HER 2 positive/Hormone receptor negative (HER 2+/HR-), HER 2+/HR+ and triple negative disease had significantly higher pCR than those with HR+/HER 2 negative disease (38.9%, 30.8%, 24.5% and 6.5% respectively, p=0.03). Conclusion: NAC resulted in pCR in about one-fifth of the entire cohort, particularly those with potentially aggressive HER 2+ and triple negative disease. The use of taxanes was associated with higher pCR rates.

Clinical Validity of a Machine Learning Decision Support System for Early Detection of Hepatitis B Virus: A Binational External Validation Study.

HepB LiveTest is a machine learning decision support system developed for the early detection of hepatitis B virus (HBV). However, there is a lack of evidence on its generalisability. In this study, we aimed to externally assess the clinical validity and portability of HepB LiveTest in predicting HBV infection among independent patient cohorts from Nigeria and Australia. The performance of HepB LiveTest was evaluated by constructing receiver operating characteristic curves and estimating the area under the curve. Delong's method was used to estimate the 95% confidence interval (CI) of the area under the receiver-operating characteristic curve (AUROC). Compared to the Australian cohort, patients in the derivation cohort of HepB LiveTest and the hospital-based Nigerian cohort were younger (mean age, 45.5 years vs. 38.8 years vs. 40.8 years, respectively; p < 0.001) and had a higher incidence of HBV infection (1.9% vs. 69.4% vs. 57.3%). In the hospital-based Nigerian cohort, HepB LiveTest performed optimally with an AUROC of 0.94 (95% CI, 0.91-0.97). The model provided tailored predictions that ensured most cases of HBV infection did not go undetected. However, its discriminatory measure dropped to 0.60 (95% CI, 0.56-0.64) in the Australian cohort. These findings indicate that HepB LiveTest exhibits adequate cross-site transportability and clinical validity in the hospital-based Nigerian patient cohort but shows limited performance in the Australian cohort. Whilst HepB LiveTest holds promise for reducing HBV prevalence in underserved populations, caution is warranted when implementing the model in older populations, particularly in regions with low incidence of HBV infection.

Human papillomavirus spectrum of HPV-infected women in Nigeria: an analysis by next-generation sequencing and type-specific PCR

BackgroundHuman papillomavirus (HPV) infection and cervical cancer are leading health problems and causes of death in many parts of the world. There are ~ 200 HPV types that can infect humans. This study aims to understand the spectrum of HPV infections in Nigerian women with normal or abnormal cytology.MethodsWe screened cervical samples from 90 women with possible HPV infections collected in two regional hospitals in Nigeria. The first screening was done using next-generation DNA sequencing (NGS), identifying multiple HPV types in many samples. Thereafter, type-specific PCR analysis was used to verify the NGS-identified HPV types in each sample.ResultsNGS analysis of the 90 samples from the Nigerian cohort identified 44 HPV types. The type-specific PCR confirmed 25 HPV types out of the 44 HPV types detected by NGS, and ~ 10 of these types were the most prevalent. The top five prevalent types found in the Nigerian cohort were HPV71 (17%), HPV82 (15%), HPV16 (16%), HPV6 (10%), and HPV20 (7%). Among the PCR-confirmed HPV types, we found 40.98% high-risk HPV types, 27.22% low-risk HPV types, and 31.15% undetermined HPV types. Among these 25 HPV types in Nigeria, only six were included in the current nine-valent HPV vaccine. We also observed strikingly high multiple HPV infections in most patients, with as many as nine HPV types in a few single samples.ConclusionsOur NGS-PCR approach of HPV typing in the Nigerian cohort samples unveiled all possible HPV types currently circulating in Nigerian people. We confirmed 25 HPV types using NGS and PCR, with many samples infected with multiple HPV types. However, only six of these types are part of the nine-valent HPV vaccines indicating the need to develop region-specific selective vaccines.

Limited emergence of resistance to integrase strand transfer inhibitors (INSTIs) in ART-experienced participants failing dolutegravir-based antiretroviral therapy: a cross-sectional analysis of a Northeast Nigerian cohort.

Due to the high prevalence of resistance to NNRTI-based ART since 2018, consolidated recommendations from the WHO have indicated dolutegravir as the preferred drug of choice for HIV treatment globally. There is a paucity of resistance outcome data from HIV-1 non-B subtypes circulating across West Africa. We characterized the mutational profiles of persons living with HIV from a cross-sectional cohort in North-East Nigeria failing a dolutegravir-based ART regimen. WGS of plasma samples collected from 61 HIV-1-infected participants following virological failure of dolutegravir-based ART were sequenced using the Illumina platform. Sequencing was successfully completed for samples from 55 participants. Following quality control, 33 full genomes were analysed from participants with a median age of 40 years and median time on ART of 9 years. HIV-1 subtyping was performed using SNAPPy. Most participants had mutational profiles reflective of exposure to previous first- and second-line ART regimens comprised NRTIs and NNRTIs. More than half of participants had one or more drug resistance-associated mutations (DRMs) affecting susceptibility to NRTIs (17/33; 52%) and NNRTIs (24/33; 73%). Almost a quarter of participants (8/33; 24.4%) had one or more DRMs affecting tenofovir susceptibility. Only one participant, infected with HIV-1 subtype G, had evidence of DRMs affecting dolutegravir susceptibility-this was characterized by the T66A, G118R, E138K and R263K mutations. This study found a low prevalence of resistance to dolutegravir; the data are therefore supportive of the continual rollout of dolutegravir as the primary first-line regimen for ART-naive participants and the preferred switch to second-line ART across the region. However, population-level, longer-term data collection on dolutegravir outcomes are required to further guide implementation and policy action across the region.

Acromioclavicular Joint Space Size in a Nigerian Patient cohort

Objective: To establish normative data on the width of the acromioclavicular (AC) joint space using sonography, based on a selected Nigerian cohort without any shoulder injury or pathology. Materials and Methods: A cross-sectional study was conducted on the normal AC joints of randomly selected Nigerians. A sonographer performed the examination and obtained all the width measurements of AC joint space, using a GE LOGIQP6 ultrasound system and a multiple-frequency linear transducer. Results: The width of the AC joint space was equal on both sides, measuring 5.6 ± 1.2 mm for the right and 5.6 ± 1.2 mm for the left ( P = .701). The mean width of both joint spaces differed between men and women, with the men having a wider space ( P &lt; .05). Age had a strong negative predictive relationship, with the AC joint space width and both joint spaces decreasing with age ( P &lt; .001). Weight and body mass index had weak negative predictive relationships with both joint space widths ( P &lt; .001). Participant height had a very weak positive predictive relationship with both joint space widths ( P &lt; .05). Conclusion: Normative data on the width of the AC joint space, in a randomly selected Nigerian cohort, are provided and may be clinically useful in the ongoing sonographic assessment of the AC joint.

Prevalence and patterns of breast white adipose tissue inflammation among American Black women and indigenous Nigerian women with early-stage breast cancer.

e12560 Background: Racial disparities in breast cancer outcomes pose a major public health challenge. Complex interactions between social determinants of health and tumor biology, mediated by obesity and adiposity, may play an important role in these disparities. White adipose tissue inflammation (WATi) of the breast, which is histologically defined by the presence of crown-like structures (CLS-B), occurs in the setting of excess adiposity and promotes tumor growth via elevated levels of aromatase, proinflammatory growth factors, and metabolic dysregulation. Here we examined relationships between race, body mass index (BMI), and WATi in two cohorts of patients with early-stage breast cancer: 1) American Black women and 2) indigenous Nigerian women. Methods: Non-tumor breast WAT specimens were collected from patients undergoing mastectomy for treatment or prevention of breast cancer at Memorial Sloan Kettering Cancer Center (MSK) in the US and Obafemi Awolowo University Teaching Hospital (OAUTH) in Nigeria. WATi was defined by the presence of CLS-B as detected by CD68 immunostaining. All tissue analyses were performed at MSK. Associations among BMI and WATi were tested within each cohort using Kendall’s tau rank correlation and compared between cohorts using Pearson's Chi-squared test. Results: A total of 224 American women were enrolled at MSK between 2011-2018, of whom 39 self-reported Black race. At OAUTH, 97 Nigerian women were enrolled between 2018-2022. Invasive carcinoma was present in 32 American Blacks and 97 Nigerians. Of those with invasive carcinoma, the prevalence of WATi among American Black women was 72% vs. 37% in the Nigerian cohort ( p&lt;0.001). In the US cohort, there was no significant difference between the prevalence of WATi among Black vs. non-Black patients (72% vs. 62%; p=0.3). 44% of American Blacks were obese and 34% overweight compared with 27% and 39% of Nigerians, respectively (p=0.07). The prevalence of WATi varied by BMI category within each cohort, as shown. Overweight/obesity was associated with WATi in the Nigerian (p=0.009) and American cohorts (p&lt;0.001); a trend was observed in the American Black subgroup (p=0.13). Conclusions: Breast WATi and obesity were more prevalent among American Black women with breast cancer compared with Nigerian women. These findings highlight the need for further investigation of environment, lifestyle patterns, and body composition differences between indigenous and diaspora populations. [Table: see text]

Abstract P2-23-17: Programmed death ligand-1 expression in triple-negative breast cancer from Nigeria

Abstract Introduction: The incidence of triple negative breast cancer (TNBC) in West Africa appears to mirror the higher incidence of the disease among African American women in the United States. However, there remains a paucity of molecular data on TNBC from sub-Saharan Africa, despite the emergence of effective immunotherapies. Methods: Consecutive patients diagnosed with invasive breast cancer between March 2018-Jan 2020 were identified from a prospective clinical database and paired biobank at Obafemi Awolowo University Teaching Hospital (OAUTH). All specimens were processed and fixed in formalin within 60 minutes of excision by a trained pathologist. Tissue sections (4μm thick) representative of tumor were selected for routine evaluation of estrogen, progesterone and human epidermal growth factor receptor-2 expression by immunohistochemistry. This was performed at OAUTH with adequate controls according to the ASCO/CAP guidelines and verified at an outside institution for quality assurance. Additional sections from the FFPE blocks of TNBC specimens were further stained using the Dako PharmDx 22C3 PD-L1 commercial assay according to manufacturer protocols at Dalhousie University. External on-slide controls included tonsil, PD-L1 negative TNBC, and PD-L1 positive TNBC. PD-L1 expression was scored using the combined positive score (CPS), which is the number of 22C3 staining tumour cells, lymphocytes, and macrophages divided by the number of viable tumour cells, multiplied by 100. The threshold for a positive result was a CPS of ≥10 as per manufacturer instructions and institutional protocol. Research ethics board approval as well as data and material transfer agreements between institutions was obtained for this study. Results: From 85 cases, 32 were TNBC (37.6%). The mean age and BMI were 49.6±SD 7.7 and 26.2±5.7, respectively. The majority of patients presented with locally advanced disease (64.2% Stage III, 14.2% Stage IV). Seventy-nine percent (78.5%) of patients received an average of five cycles of neoadjuvant chemotherapy (SD 2.3). From 32 TNBC specimens, 27 had available FFPE tissue blocks, and of those, 24 had interpretable PD-L1 IHC for inclusion in the analysis. A total of 37.5% (9/24) of cases demonstrated a CPS ≥10. Conclusions: Over a third of breast cancer specimens in this Nigerian cohort were triple negative, 37.5% of which had PD-L1 CPS scores of ≥10. These results suggest a large proportion of patients in Nigeria may benefit from access to immunotherapy. This is the first reported incidence of PD-L1 expression in breast cancer from sub-Saharan Africa. Citation Format: Olalekan Olasehinde, Funmilola Wuraola, Aleksandra Kajetanowicz, Gilllian Bethune, Marcia Edelweiss, Peter Ntiamoah, Oluwole Odujoko, Avinash Sharma, Victoria Mango, Peter Kingham, Olusegun Alatise, Gregory Knapp. Programmed death ligand-1 expression in triple-negative breast cancer from Nigeria [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-23-17.

Prevalence and determinants of lymphedema in newly diagnosed Nigerian breast cancer patients using bioimpedance estimations.

Breast cancer-related lymphedema (BCRL) is common and has significant impact on quality of life. Very little is known about BCRL in sub-Saharan Africa. Generally, BCRL has been mostly evaluated post treatment, with very limited data on the prevalence of pre-treatment BCRL at baseline. This study presents the prevalence and clinical associations of lymphedema among newly diagnosed, treatment-naive breast cancer patients in a Nigerian cohort using bioimpedance estimations. Consecutively consenting, newly diagnosed, treatment-naive breast cancer patients were assessed for upper limb lymphedema using bioimpedance measurements of the extracellular fluid and the single-frequency bioelectrical impedance analysis value at 5 kHz. Patients were classified as having lymphedema if there was >10% difference in arm measurements or if the ratios of the arm measurements were >3 SD above a normative mean generated from representative controls. Regression analysis was performed to determine clinical variables associated with lymphedema. There were 154 breast cancer patients with a median age of 47 (40.0-56.8) years and a body mass index of 27 (23.5-30.9) kg/m2. The majority (70%) had stage III disease. All measurements were significantly higher in cases than controls. Using various definitions, the prevalence of lymphedema was between 11.7% and 14.3%. Various clinical variables relating to clinical stage were significantly associated with lymphedema. The predominance of locally advanced disease in the Nigerian setting is associated with high pre-treatment lymphedema rates. This may set the stage for higher rates in the post-operative setting. Management of lymphedema should be incorporated into the treatment planning.

Unique microbial biomarkers identified in Nigerian patients with colorectal cancer.

222 Background: The microbiome is an important biomarker associated with the pathogenesis and progression of disease in colorectal cancer (CRC). Genetic, dietary and environmental factors have been implicated in CRC microbial dysbiosis, however geographical distinctions in the microbiome of CRC are largely unknown. In this study, we characterize distinctions in the microbial diversity and microbial enrichment of CRC specimen obtained from a Nigerian and U.S. population. Methods: A validated microbiome bioinformatics pipeline that is generalizable across multiple next generation sequencing platforms was utilized. Microbial profiles for alpha diversity and enrichment were generated for two large, geographically distinct cohorts: (1) U.S. (n=498) and (2) Nigerian (n=65) cohorts. CRC specimen from Nigeria were compared to CRC specimen from the U.S. using the same microbial bioinformatics pipeline and methodology for analysis. Microbial differences stratified based on CRC microsatellite-instability (MSI) status were identified. Results: 9 unique microbial species were significantly enriched in the CRC specimen from the Nigerian cohort when compared to the US cohort. Subset analysis based on MSI status revealed enrichment of Faecalibacterium and Veillonella in the Nigerian cohort for both MSI and microsatellite stable (MSS) CRC (Table). Prevotella was significantly enriched in MSS CRC in the Nigerian cohort (OR=53.35, CI=10.34,275.37, p&lt;0.001). There were no significant differences in alpha diversity between the Nigerian and U.S. cohorts (p&gt;0.05). Conclusions: Several unique species with taxonomic diversity are enriched in Nigerian CRC and can be independently validated based on stratification by MSI status. Given the varied accessibility of diagnostic and therapeutic tools for CRC in these distinct geographical settings, understanding unique microbial biomarkers will provide the landscape to explore key microbial targets for therapy specific to this population.[Table: see text]

Metabolic Syndrome in HIV: Prevalence, correlates, concordance of Diagnostic Criteria and relationship to Carotid Intimal Media Thickness in a Sub-Saharan Population.

The prevalence and usefulness of MetS in determining CVD risk in at-risk populations are influenced by its definition. In a cohort of HIV-positive Nigerians, we evaluated MetS based on various defining criteria, their agreement with one another, and their association to a CVD endpoint, Carotid-Intimal-Media-Thickness (CIMT). In this cross-sectional study, 145 HIV-positive individuals who were enrolled in HIV clinics at the Faith Alive Foundation and Jos University Teaching Hospital in Jos, Nigeria, were randomly chosen. Biophysical and anthropometric measurements including blood pressure, height, weight, waist circumference, and hip-circumference, as well as clinical records, CIMT, fasting plasma glucose, and lipid profile, were assessed. The median (Interquartile range) age of the participants was 41 (35-88) years, and the majority (71.7%) were females. The prevalence of metabolic syndrome (MetS) by the Adult Treatment Panel-III (ATP), International Diabetes Federation (IDF), and Joint Interim Statement (JIS) criteria were 30.3%, 32.4%, and 35.2% respectively. MetS by all criteria was more prevalent among females and participants ≥ 40 years, p<0.05. Low HDLc (93.6-95.5%), Central obesity (86.3-95.5%), and hypertension (80.9-86.4%) were the most frequent components of MetS. HIV-related parameters were not associated with MetS. The overall agreement among MetS criteria was almost perfect between IDF and JIS criteria (k=0.94); and strong between IDF vs., ATP (k=0.82) and ATP vs. JIS (k=0.89). There was no significant difference in the median CIMT in PLHIV with and without MetS across all defining criteria. The prevalence of MetS in PLHIV is relatively high, particularly among females and older individuals. The correlations between the defining criteria were fairly strong and consistent across subpopulations of PLHIV. MetS based on these criteria, however, do not significantly correlate with rising CIMT.

Prevalence and Predictors of Post-Thyroidectomy Voice Dysfunction in a Nigerian Cohort.

Advances in surgical techniques have significantly improved the safety of thyroidectomy. Quality of life issues, such as voice changes, however continue to be important considerations. This study evaluated the prevalence and determinants of voice changes following thyroidectomies for non-malignant goiters in a Nigerian Hospital. Consecutive adults who had thyroidectomy for non-malignant goiters were evaluated. Preoperatively, each participant had laryngoscopy and voice assessment using the Voice Handicap Index-10. At surgery, the intubation difficulty score, size of endotracheal tubes, and duration of operation were recorded. Laryngoscopy and VHI-10 assessments were repeated 1week, 1month, and 3months after surgery. Pre and postoperative assessments were compared. Fifty-four patients completed the study. Subtotal thyroidectomy was the commonest operation performed in 17 patients (31.48%), with 14 (25.93%) having total thyroidectomy. Baseline median VHI-10 score was 6.5(IQR-10). Five patients had abnormal preoperative laryngoscopy findings (benign vocal cord lesions). Postoperatively, seven patients had endoscopic evidence of vocal cord paralysis, six were unilateral while one was bilateral. Ten patients (18.5%) had early voice changes. Median VHI-10 score at one week was significantly higher than baseline (10 vs. 6.5, p = 0.01). At 3months, VHI-10 reverted back to baseline in five of the ten patients while five patients (9.3%) had persistent voice changes. Abnormal endoscopic findings predicted the occurrence of early postoperative voice changes. Thyroidectomy for non-malignant goiters is associated with transient voice changes, many of which revert to normal over time. Abnormal endoscopic findings predict its occurrence.

Clinicopathological features and androgen receptor expression in triple negative breast cancer at Lagos, Nigeria.

Androgen receptor (AR) is one of the predominant nuclear hormone receptors in invasive breast cancer and can be explored as a biomarker of response for targeted anti-androgen therapy, especially in the setting of triple negative breast cancer (TNBC). Luminal AR is a distinct subtype amongst TNBC cases following gene expression studies. TNBC is higher in Africans (23%-82%) and African-Americans (29.8%) compared to Caucasian (10%-15%) breast cancer patients; however, there is a paucity of data on AR expression in this population. The aim of this study is to determine the expression of AR and the proportion of AR positive cancers in TNBCs at the Lagos University Teaching Hospital, Lagos, Nigeria. Out of 99 reviewed cases, 78 formalin fixed, paraffin embedded TNBC cases were assembled into a tissue microarray, stained and analysed for AR expression using immunohistochemistry. The mean age of the TNBC patients was 49.3 years (range: 20-80 years). The histologic types in this study were invasive carcinoma (no special type) 75.4%; metaplastic carcinoma 21.4%; lobular carcinoma and mucinous carcinoma 1.6% each. Of 61 TNBC cases analysed, 37.7% were AR positive and 62.3% were AR negative, making the latter to become quadruple negative breast cancers. There was a significant association between age and AR expression (p = 0.02). In the subjects that expressed AR positivity, patients below 50 years accounted for 34.8% (8 of 23) while 65.2% (15 of 23) were above 50 years. There was no significant association between AR expression and histologic type or tumour grade. Over a third of this Nigerian TNBC cohort study is AR+. This warrants further exploration of the predictive and prognostic significance of its expression amongst TNBC and the potential for targeted therapy, specifically androgen antagonists to improve the outcome of this disease with limited therapeutic options.

Fetal Fibronectin as a Predictor of Preterm Delivery: A Nigerian Cohort Study.

Background Fetal fibronectin is a useful biomarker in the diagnosis and management of preterm labour. Objectives To evaluate the relationship between cervical fetal fibronectin and preterm delivery and the association between cervical fetal fibronectin level and gestational age at delivery. Materials and Methods A prospective cohort study was performed in a tertiary hospital in Nigeria, involving equal number of pregnant women with (96) and without (96) preterm labour. Fetal fibronectin assay was done using solid-phase immunogold assay. The data were analysed using IBM SPSS version 24. Descriptive and inferential statistical analyses were done. The level of significance was p-value <0.05. Results Less than half (47.9%) of the women in the study group had preterm delivery while 13.09% of the women in the control group delivered preterm. Fetal fibronectin test had a sensitivity, specificity, positive predictive value and negative predictive value of 78%, 86.5%, 71.9%, and 89.0%, respectively, a positive likelihood ratio and negative likelihood ratio of 5.76(95% CI, 3.67 – 9.64) and 0.26(95% CI, 0.16 – 0.41), respectively. Conclusion The findings in our study value of fetal fibronectin in predicting preterm delivery. Its use will support less intervention for patients with negative results.

Breast Cancer in a Nigerian Cohort: Histopathology, Immunohistochemical Profile and Survival

Aims: The aim was to describe the histological and immunohistochemical characteristics of breast cancer in a Nigerian cohort and correlate the findings with the clinical outcome of management.Methods and results: The histology of 89 breast cancers was reviewed. Immunohistochemistry (IHC) for estrogen receptor (ER) and Her2/neu was done on 73 cases and progesterone receptor (PR) on 67cases. Age ranged from 22-82 years (mean = 48±12.3).Invasive ductal carcinoma of no special type (NOS) was the commonest histological variant. Sixty two cases (69.7%) were grade III tumours. IHC was negative for ER in 62%, PR 79%. Her2/neu over-expression was seen in only 4%. About 53% (31/58) of the tumourswere negative for all the three markers. At presentation, 68.2% of the patients had stage III and stage IV disease. After 5 years of follow up, 20% of the ER/PR positive patients were dead, 10% had local recurrences and 70% were lost to follow-up. Among the triple negativepatients, 50% were alive and well with no recurrence, 20% were dead and 30% were lost to follow-up. All the patients with Her2 positive tumours were dead within 1-2 years.Conclusion: Our data suggest that breast cancer in Nigeria occurs at younger age, is of high histological grade and is more likely to be triple negative. Clinical outcome tends to be good among the triple negative patients with early stage disease.

Abstract 1507: Tumor only analysis of whole exome sequencing from a multi-institutional Nigerian prostate cancer cohort reveals DNA repair genes associated with African ancestry

Abstract Men of African ancestry (MAA) have the highest global incidence and mortality of prostate cancer (PCa); however, the biology underlying this harsh disease presentation remains poorly understand, largely due to Africans and people within the African diaspora being under-represented in genomics research. MAA are younger at diagnosis, have higher tumor volume at diagnosis and have higher tumor aggression compared to European American men. Additionally, genomic profiling continues to show that PCa etiology and phenotype are influenced by higher amounts of African ancestry and that West African ancestry is associated with unique genomic alterations. Herein we utilize whole exome sequencing of a unique cohort of 45 advanced stage, treatment naïve Nigerian primary PCa tumors and 11 unmatched non-tumor tissue to compare genomic variants with African (AA) and European (EA) American TCGA PCa tumors. Nigerian samples were collected from 6 sites in central and southwest Nigeria. After whole exome sequencing, samples were processed using GATK best practices. Four genes [BRCA1 (100%), BARD1 (45%), BRCA2 (27%) and PMS2 (18%)] had germline variants in at least two Nigerian non-tumor samples. Across 111 germline variants, the AA cohort reflected a pattern [BRCA1 (68%), BARD1 (34%), BRCA2 (28%) and PMS2 (16%)] similar to Nigerian samples. Of the most frequently mutated genes, BRCA1 showed a statistically (p ≤ 0.05) higher mutation frequency in MAA. Disaggregating gene level mutation frequencies by variant revealed both ancestry linked and Nigerian specific germline variant patterns. Driven by rs799917, BRCA1 showed increasing mutation frequency as African admixture increased. BRCA2_rs11571831 was only present in MAA and BRCA2_rs766173 was increased in Nigerian men. 133 somatic variants were present in 26 PCa associated genes within the Nigerian tumor cohort. Nine genes [BRCA2 (27%), APC (20%), ATM (20%), BRCA1 (13%), DNAJC6 (13%), EGFR (13%), MAD1L1 (13%), MLH1 (11%) and PMS2 (11%)] showed mutation frequencies above 10%. Compared to TCGA cohorts, BRCA2, APC and BRCA1 showed statistically significant increases in Nigerian tumors. The Nigerian cohort variant pattern shared similarities (cosign similarities ≥ 0.734) with COSMIC signatures 5 and 6 and mutated genes showed significant (q &amp;lt; 0.001) GO and functional enrichment in mismatch repair and non-homologous repair deficiency (HRD) pathways. Here, we show that variants in DDR genes are increased in Nigerian PCa and that a portion of those variants correlate with increased African ancestry. Moreover, we identify variants of unknown significance that may contribute to population specific routes of tumorigenesis and treatment. These results present the most comprehensive characterization of the Nigerian PCa exome to date and further highlight the need to increase study population diversity. Citation Format: Jason A. White, Ernest Kaninjing, Kayode A. Adeniji, Paul Jibrin, John O. Obafunwa, Chidiebere N. Ogo, Mohammed Faruk, Solomon Rotimi, Ademola Popoola, Omolara A. Fatiregun, Olabode P. Oluwole, Balasubramanyam Karanam, Wei Tang, Stefan Ambs, Folake T. Odedina, Damali N. Martin, Clayton Yates. Tumor only analysis of whole exome sequencing from a multi-institutional Nigerian prostate cancer cohort reveals DNA repair genes associated with African ancestry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1507.