A framework for advancing sustainable magnetic resonance imaging access in Africa.

Magnetic resonance imaging (MRI) technology has profoundly transformed current healthcare systems globally, owing to advances in hardware and software research innovations. Despite these advances, MRI remains largely inaccessible to clinicians, patients, and researchers in low-resource areas, such as Africa. The rapidly growing burden of noncommunicable diseases in Africa underscores the importance of improving access to MRI equipment as well as training and research opportunities on the continent. The Consortium for Advancement of MRI Education and Research in Africa (CAMERA) is a network of African biomedical imaging experts and global partners, implementing novel strategies to advance MRI access and research in Africa. Upon its inception in 2019, CAMERA sets out to identify challenges to MRI usage and provide a framework for addressing MRI needs in the region. To this end, CAMERA conducted a needs assessment survey (NAS) and a series of symposia at international MRI society meetings over a 2-year period. The 68-question NAS was distributed to MRI users in Africa and was completed by 157 clinicians and scientists from across Sub-Saharan Africa (SSA). On average, the number of MRI scanners per million people remained at less than one, of which 39% were obsolete low-field systems but still in use to meet daily clinical needs. The feasibility of coupling stable energy supplies from various sources has contributed to the growing number of higher-field (1.5 T) MRI scanners in the region. However, these systems are underutilized, with only 8% of facilities reporting clinical scans of 15 or more patients per day, per scanner. The most frequently reported MRI scans were neurological and musculoskeletal. The CAMERA NAS combined with the World Health Organization and International Atomic Energy Agency data provides the most up-to-date data on MRI density in Africa and offers a unique insight into Africa's MRI needs. Reported gaps in training, maintenance, and research capacity indicate ongoing challenges in providing sustainable high-value MRI access in SSA. Findings from the NAS and focused discussions at international MRI society meetings provided the basis for the framework presented here for advancing MRI capacity in SSA. While these findings pertain to SSA, the framework provides a model for advancing imaging needs in other low-resource settings.

The performance of machine learning approaches for attenuation correction of PET in neuroimaging: A meta-analysis.

PURPOSE: This systematic review provides a consensus on the clinical feasibility of machine learning (ML) methods for brain PET attenuation correction (AC). Performance of ML-AC were compared to clinical standards. METHODS: Two hundred and eighty studies were identified through electronic searches of brain PET studies published between January 1, 2008, and August 1, 2022. Reported outcomes for image quality, tissue classification performance, regional and global bias were extracted to evaluate ML-AC performance. Methodological quality of included studies and the quality of evidence of analysed outcomes were assessed using QUADAS-2 and GRADE, respectively. RESULTS: A total of 19 studies (2371 participants) met the inclusion criteria. Overall, the global bias of ML methods was 0.76 ± 1.2%. For image quality, the relative mean square error (RMSE) was 0.20 ± 0.4 while for tissues classification, the Dice similarity coefficient (DSC) for bone/soft tissue/air were 0.82 ± 0.1 / 0.95 ± 0.03 / 0.85 ± 0.14. CONCLUSIONS: In general, ML-AC performance is within acceptable limits for clinical PET imaging. The sparse information on ML-AC robustness and its limited qualitative clinical evaluation may hinder clinical implementation in neuroimaging, especially for PET/MRI or emerging brain PET systems where standard AC approaches are not readily available.

Immune reconstitution inflammatory syndrome-associated Graves disease in HIV-infected patients: clinical characteristics and response to radioactive iodine therapy.

OBJECTIVES: We aimed to describe the clinical characteristics and the response to radioactive iodine (RAI) treatment of immune reconstitution inflammatory syndrome-associated Graves disease (IRIS-GD) in comparison to Graves disease (GD) seen in HIV-uninfected patients. METHODS: We retrospectively reviewed the medical records of patients treated with RAI for GD. We obtained clinical, biochemical and HIV-related information of patients from their medical records. We compared patient characteristics and response to RAI treatment between patients with IRIS-GD and GD seen in HIV-uninfected patients. RESULTS: A total of 253 GD patients, including 51 patients with IRIS-GD, were included. Among IRIS-GD patients, CD4 cell nadir was 66 cells/µL (range: 37-103) with a peak HIV viral load of 60 900 copies/mL (range: 36 542-64 500). At the time of diagnosis of IRIS-GD, all patients had a completely suppressed HIV viraemia with a CD4 cell count of 729 cells/µL (range: 350-1279). The median interval between the commencement of HIV treatment and the onset of GD was 63 months. At 3 months follow-up, the proportion of patients with IRIS-GD achieving a successful RAI treatment outcome (euthyroid/hypothyroid state) was lower than that of HIV-uninfected patients (35.3% vs. 63.4%, respectively; p < 0.001). The response rate remained lower (60.8%) among patients with IRIS GD than among HIV-uninfected GD patients (80.2%, p = 0.004) at 6 months follow-up. After correcting for differences in age, gender and pre-treatment thyroid-stimulating hormone level, there was no significant difference in RAI treatment response between the two groups. CONCLUSIONS: After correcting for possible confounders, the response to RAI treatment was not different between patients with IRIS-GD and GD in HIV-uninfected patients.

Immunohistochemical Profiling of HER-2/neu, Steroid Hormone Receptors and KI-67 Biomarkers in A Cohort of Nigerian Women with Breast Cancer.

Background: Progressive improvement in the accuracy of profiling of hormone receptors in breast cancer provides the basis for targeted endocrine therapy, a major pillar of multimodal breast cancer treatment. However, the disparity in findings from comparatively smaller sample-sized studies in West Africa has led to somewhat conflicting conclusions and recommendations. Objectives: This study investigates the immunohistochemical (IHC) profile of breast cancer specimens for estrogen receptor (ER), progesterone receptor (PR), human epidermal receptor-2 (HER2)/neu, and Ki-67 in a tertiary hospital in Ibadan, Nigeria over 12 years. Materials and Methods: We reviewed 998 IHC reports, documented clinicopathologic parameters, computed patterns of biomarkers, and stratified them based on the American Society of Clinical Oncology/College of American Pathologists recommendations. Descriptive analysis including frequency, mean, and median were generated from the data extracted. Results: Out of the 998 cases, 975 (97.7%) were females and 23 (2.3%) were males. The mean age was 48.84 ± 11.99 years. Open biopsies were the most common types of specimens (320, 41.6%): lumpectomy and incisional biopsy of ulcerated, fungating or unresectable tumours. In those cases, 246 (32.0%) were samples of breast-conserving or ablative surgical extirpation (mastectomy/wide local excision/quadrantectomy), and 203 (26.4%) were obtained by core needle biopsies. Invasive ductal carcinoma was the most common histopathological type (673, 94.5%). The majority of graded tumours were intermediate grade (444, 53.5%). Four hundred and sixty-nine (48.4%) were ER positive, 414 (42.8%) were PR positive, and 180 (19.4%) were HER2/neu positive. Three hundred and thirty-four (34.0%) were triple-negative. Eighty-nine cases had Ki-67 staining done, and of these 61 (68.5%) had positive nuclear staining. Conclusion: Steroid hormone receptors and HER-2/neu proportions in our cohort are likely to be more representative than the widely varied figures hitherto reported in the sub-region. We advocate routine IHC analysis of breast cancer samples as a guide to personalized endocrine therapy.

Characteristics and outcomes of patients hospitalized with COVID-19 at a tertiary hospital in Nigeria.

Background: Data regarding the features and outcomes of hospitalized COVID-19 patients in Africa are increasingly available. Objectives: To describe socio-demographic, clinical and laboratory characteristics and outcomes of COVID-19 patients. Methods: A cross-sectional study of 86 adult patients hospitalized with COVID-19 between March and November 2020. Characteristics were described in survivors and non-survivors. Results: Mean age was 60.9±16.1 years, 53(61.6%) were male. Co-morbidities were found in 77(89.5%) patients. On severity, 6(7%) were mild, 23(26.7%) moderate, 51(59.3%) severe and 6(7%) critical. Oxygen saturation and respiratory rate were 71±22% and 38±11/minute in non-survivors and 90±7% and 31±7/minute in survivors respectively (p<0.001, p<0.001)). Overall mortality was 47.7% with no death among patients with mild disease and deaths in all patients with critical disease. Duration of hospitalization was 2.0(1.0-4.5) days in those who died and 12(7.0-15.0) days in those who survived (p<0.001). Of the 42 patients that received dexamethasone, 11(26.2%) died, while 31(73.8%) survived (p=<0.001). Conclusion: Most of the patients had co-morbidities and there was high mortality in patients with severe and critical COVID-19. Mean oxygen saturation was low and respiratory rate high overall. Factors associated with mortality included: Significantly greater hypoxia and tachypnea, less dexamethasone use and shorter hospitalization.

A Bone Scan Is Valuable for Primary Staging of Newly Diagnosed Prostate Cancer in a Low-Resource Setting (Nigeria).

Objective: There is a paucity of information on bone scanning for prostate cancer from low-resource countries. This study evaluated the role of bone scan in the primary staging of newly diagnosed prostate cancer in one such setting. Methods: A retrospective analysis of 126 men with newly diagnosed prostate cancer undergoing an initial staging bone scan between January 2017 and December 2020 was carried out at a regional nuclear medicine center in Nigeria. Bone scan results were analyzed according to age, serum level of baseline prostate-specific antigen (PSA), and Gleason score. Equivocal scans and patients with no Gleason score or baseline PSA were excluded from the analysis. p < 0.05 was said to be significant statistically. Results: Of 111 patients (aged 38-84 years, median 66 years), who met the inclusion criteria, 26 (23%) men had evidence of bony metastases as shown by a positive bone scan. Higher PSA levels and Gleason scores were associated with an increased risk of a positive bone scan, p < 0.001. No patient with a PSA level < 20 ng/mL and a Gleason score of < 7 had a positive bone scan. Conclusion: The role of bone scanning in staging newly diagnosed prostate cancer patients in Nigeria is consistent with global reports. Our study confirms that a bone scan finding is well associated with the risk classification using PSA and Gleason score in our population.

Pattern of Prostate Cancer Recurrence Assessed by 68Ga-PSMA-11 PET/CT in Men Treated with Primary Local Therapy.

Imaging plays a vital role in detecting the recurrence of prostate cancer (PCa) to guide the choice of salvage therapy. Gallium-68 prostate-specific membrane antigen positron-emission tomography/computed tomography (68Ga-PSMA-11 PET/CT) is useful for detecting PCa recurrence. We assessed the pattern of PCa recurrence stratified by serum prostate-specific antigen level and type of primary local treatment in men with biochemical recurrence (BCR) after primary local therapy with radical prostatectomy or external beam radiotherapy (EBRT) using 68Ga-PSMA-11 PET/CT. We reviewed patients imaged with 68Ga-PSMA-11 PET/CT for the localization of the site of PCa recurrence. We determined the site and number of lesions due to PCa recurrence at different PSA levels. A total of 247 men (mean age of 65.72 ± 7.51 years and median PSA of 2.70 ng/mL (IQR = 0.78-5.80)) were included. 68Ga-PSMA-11 PET/CT detected the site of recurrence in 81.4% of patients with a median number of lesions per patient of 1 (range = 1-5). 68Ga-PSMA-11 PET/CT positivity was 43.6%, 75.7%, 83.3%, 90.0%, and 95.8% at PSA levels of <0.5, 0.5-1.0., 1.1-2.0, 2.1-5.0, and 5.0-10.0, respectively. The most common site of recurrence was in the prostate gland/bed at all PSA levels. Pelvic, extra-pelvic, and combined pelvic and extra-pelvic sites of recurrence were seen in 118, 50, and 33 patients, respectively. The risk of extra-pelvic recurrence increases with rising PSA levels. 68Ga-PSMA-11 PET/CT has a high lesion detection rate for biochemical recurrence of PCa in patients previously treated with primary local therapy.

MicroRNA-1205 Regulation of FRYL in Prostate Cancer.

High mortality rates of prostate cancer (PCa) are associated with metastatic castration-resistant prostate cancer (CRPC) due to the maintenance of androgen receptor (AR) signaling despite androgen deprivation therapies (ADTs). The 8q24 chromosomal locus is a region of very high PCa susceptibility that carries genetic variants associated with high risk of PCa incidence. This region also carries frequent amplifications of the PVT1 gene, a non-protein coding gene that encodes a cluster of microRNAs including, microRNA-1205 (miR-1205), which are largely understudied. Herein, we demonstrate that miR-1205 is underexpressed in PCa cells and tissues and suppresses CRPC tumors in vivo. To characterize the molecular pathway, we identified and validated fry-like (FRYL) as a direct molecular target of miR-1205 and observed its overexpression in PCa cells and tissues. FRYL is predicted to regulate dendritic branching, which led to the investigation of FRYL in neuroendocrine PCa (NEPC). Resistance toward ADT leads to the progression of treatment related NEPC often characterized by PCa neuroendocrine differentiation (NED), however, this mechanism is poorly understood. Underexpression of miR-1205 is observed when NED is induced in vitro and inhibition of miR-1205 leads to increased expression of NED markers. However, while FRYL is overexpressed during NED, FRYL knockdown did not reduce NED, therefore revealing that miR-1205 induces NED independently of FRYL.

Underutilisation of nuclear medicine scans at a regional hospital in Nigeria: need for implementation research.

BACKGROUND: Nuclear medicine needs better integration into the Nigerian health system. To understand the relevant public health initiatives that will be required, this study assessed the pattern of nuclear medicine imaging services at the first nuclear medicine centre in Nigeria from January 2010 to December 2018. METHODS: The data of consecutive nuclear medicine (NM) scans performed between 1st January 2010 and 31st December 2018 at the NM department in a tertiary hospital in Nigeria were extracted from patient records and analysed using SAS version 9.4 (SAS Institute, Cary, NC). The National Cancer Institute's Joinpoint software and QCIS (QGIS project) were used to estimate imaging trends and geographical spread of patients. RESULTS: An average of 486 scans per year was performed during the study period. Patients travelled from 32 of Nigeria's 36 states, and the majority (65%) travelled more than 100 km to obtain NM scans. Bone scans accounted for 88.1% of the studies. The remainder were renal scintigraphy (7.3%), thyroid scans (2.5%), whole-body iodine scans (1.7%) and others (0.4%). CONCLUSIONS: NM in Nigeria appears underutilised. Furthermore, the studies to characterise the access gaps and implementation needs will contribute to the design of practical strategies to strengthen NM services in Nigeria.

FDG PET/CT for evaluating systemic arterial inflammation induced by anthracycline-based chemotherapy of Hodgkin lymphoma: A retrospective cohort study.

To evaluate arterial fluorodeoxyglucose (FDG) uptake as a marker of arterial inflammation in multiple vascular beds in patients treated with anthracycline-based chemotherapy for Hodgkin lymphoma (HL).We used maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR) to quantify arterial FDG uptake in the carotid artery, ascending aorta, abdominal aorta, and femoral artery obtained on positron emission tomography/computed tomography (PET/CT) imaging performed at baseline before chemotherapy and after completion of chemotherapy in patients with HL treated with an anthracycline-containing regimen. We compared the SUVmax and TBR obtained at baseline with that obtained post-chemotherapy for each arterial bed to evaluate the effect of anthracycline-based chemotherapy. We evaluated the effect of cardiovascular risk factors such as human immunodeficiency virus (HIV) infection, smoking, hypertension, and diabetes on the changes in SUVmax and TBR seen in the different arterial beds after anthracycline-based chemotherapy.Fifty-two patients were included with a mean age of 34.56 ±â€Š10.19 years. There were 33 males, and 18 patients were HIV-infected. The mean interval between completion of chemotherapy and follow-up flourine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) scan was 65 weeks. We found no significant difference in arterial FDG uptake measured by SUVmax and TBR in all arterial beds between the pre- and post-chemotherapy FDG PET/CT. There was no significant impact of HIV infection, smoking, and hypertension on the changes in arterial FDG uptake following treatment with anthracycline-based chemotherapy.In patients with HL who were treated with anthracycline-based chemotherapy, we found no significant increase in arterial inflammation measured by FDG PET/CT after an average follow-up period of about 65 weeks since completion of chemotherapy.

Population Differentiation at the PVT1 Gene Locus: Implications for Prostate Cancer.

Genetic variation in susceptibility to complex diseases, such as cancer, is well-established. Enrichment of disease associated alleles in specific populations could have implications for disease incidence and prevalence. Prostate cancer (PCa) is a disease with well-established higher incidence, prevalence, and worse outcomes among men of African ancestry in comparison to other populations. PCa is a multi-factorial, complex disease, but the exact mechanisms for its development and progression are unclear. The gene desert located on chromosome 8q24 is associated with aggressiveness of PCa. Interestingly, the non-protein coding gene locus Plasmacytoma Variant Translocation (PVT1) is present at chromosome 8q24 and is overexpressed in PCa. PVT1 gives rise to multiple transcripts with potentially different molecular and cellular functions. In an analysis of the PVT1 locus using data from the 1000 Genomes Project, we found the chromosomal region spanning PVT1 exons 4A and 4B to be highly differentiated between African and non-African populations. We further investigated levels of gene expression of PVT1 exons 4A and 4B and observed significant overexpression of these exons in PCa tissues relative to benign prostatic hyperplasia and to normal prostate tissues obtained from men of African ancestry. These results indicate that PVT1 exons 4A and 4B may have clinical implications in PCa a conclusion supported by the observation that transient and stable overexpression of PVT1 exons 4A and 4B significantly induce greater prostate epithelial cell migration and proliferation. We anticipate that further exploration of the role of PVT1 exons 4A and 4B may lead to the development of diagnostic, therapeutic, and other clinical applications in PCa.

PVT1 Signaling Is a Mediator of Cancer Progression.

There is increasing evidence that PVT1 has oncogenic properties and regulates proliferation and growth of many cancers. Themolecular mechanisms of action of PVT1 are mediated, in part, by microRNAs (miRNAs). However, some well-established transcription factors involved in cancer cell proliferation share a common thread of microRNA associations with PVT1. Furthermore, these microRNAs are also involved in mechanisms that lead to the development of drug resistance in cancer cells. While several microRNAs have been implicated directly in PVT1-mediated tumorigenesis, significant steps need to be taken to elucidate these important relationships. We synthesize the current knowledge of the miRNAs and associated genes by which PVT1 contributes to tumorigenesis. Overall, the trend suggests a negative correlation of microRNA expression with PVT1. It is clear that future studies involving PVT1 should be carried out in conjunction with microRNA analysis and should include large scale lncRNA-miRNA-mRNA network analysis. Likewise, the relationship between established transcription factors such as p53 and MYC, and processes like epithelial-mesenchymal transition may offer valuable insight into the yet unknown mechanisms of PVTI-mediated cancer progression via microRNA-dependent signaling networks.

Long Noncoding RNA from PVT1 Exon 9 Is Overexpressed in Prostate Cancer and Induces Malignant Transformation and Castration Resistance in Prostate Epithelial Cells.

Prostate cancer (PCa) is the most common non-cutaneous cancer and second leading cause of cancer-related death for men in the United States. The nonprotein coding gene locus plasmacytoma variant translocation 1 (PVT1) is located at 8q24 and is dysregulated in different cancers. PVT1 gives rise to several alternatively spliced transcripts and microRNAs. There are at least twelve exons of PVT1, which make separate transcripts, and likely have different functions. Here, we demonstrate that PVT1 exon 9 is significantly overexpressed in PCa tissues in comparison to normal prostate tissues. Both transient and stable overexpression of PVT1 exon 9 significantly induced greater prostate epithelial cell migration, as well as increased proliferation and corresponding proliferating cell nuclear antigen (PCNA) expression. Notably, implantation into mice of a non-tumorigenic prostate epithelial cell line stably overexpressing PVT1 exon 9 resulted in the formation of malignant tumors. Furthermore, PVT1 exon 9 overexpression significantly induced castration resistance. Consequently, PVT1 exon 9 expression is important for PCa initiation and progression, and holds promise as a therapeutic target in PCa.

A sub-Saharan African experience in the surgical management of soft tissue sarcomas in an oncology unit in: a retrospective cohort study.

INTRODUCTION: Soft tissue sarcomas (STS) consist of over 70 histologic subtypes and constitute only 1% of adult malignancies. The fulcrum of management is surgical resection with neoadjuvant or adjuvant treatment-chemoradiation. METHODS: The study is a retrospective review of consecutive STS patients who had surgery at the University College Hospital, Ibadan, between October 2007-2017. Data extraction was from the admission and operative registers, theatre records and histology reports. Statistical analysis was done using the Statistical Package for Social Sciences (SPSS) version 20 (Chicago IL USA). Results were summarized as charts and graphs. RESULTS: Five hundred and ninety six cases of STS were seen over the ten-year period. Of these, 383 (64.3%) patients had surgery and the case files of 326 (85.1%) of these patients was available for review. The duration of soft tissue swelling, ranged from 1-96 months. A third of the tumors were superficial while 68% were deep-seated. Oncoplastic reconstruction was done in 42(13%) patients. The resection margin was negative in 88%. A total of 202 patients were followed up regularly for between 24-36 months only. CONCLUSION: Patients who benefitted from definitive surgical treatment for STS were found to be the young and middle age group. These patients had extended duration of symptoms with lesions > 5cm in size. Truncal and visceral STS had the worst prognosis. A Multi-Disciplinary Tumor (MDT) board for STS and a robust follow up would enhance the management of STS in a low resource setting.

68Gallium-Arginine-Glycine-Aspartic Acid and 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Chondroblastic Osteosarcoma of the Skull.

We report the case of a 32 year-old male with Chondroblastic Osteosarcoma of the skull, which was imaged with both 18[F]fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) and 68Gallium-arginine-glycine-aspartic acid (68Ga-RGD) PET/CT. The 18F-FDG PET/CT did not demonstrate the tumour, whereas the 68Ga-RGD PET/CT clearly depicted a left-sided frontal tumour. 68Ga-RGD PET/CT may be a clinically useful imaging modality for early detection of recurrent osteosarcoma, considering the limitations of 18F-FDG PET in a setting of low glycolytic activity.

Adverse Reactions to Radioiodine 131I Therapy of Goiter in West African Tertiary Hospital.

OBJECTIVE: Radioactive iodine therapy (RAIT) is established as an efficient means of treating toxic goiter (TG) globally. The field of nuclear medicine (NM) still appears novel to many Nigerian clinicians and patients. A culturally embedded dread of radiation may raise ethical and moral concerns about potential adverse effects in the wake of RAIT in our setting. An adverse drug reaction may be described as "a response to a drug which is noxious and unintended, and which occurs at doses normally used in man". This study therefore, seeks to review adverse reactions (ARs) experienced following RAIT. We would also like to improve patient and physician education about the safety profile of RAIT. METHODS: This is a retrospective analysis of all patients who had received RAIT for thyroid disease from August 2006 to June 2015. RESULTS: Forty typical ARs were experienced following 36 therapy sessions (18.65%) with RAIT in 35 patients (21.47%) aged 17-78 years, of which three had multiple sessions for well-differentiated thyroid carcinoma (WDTC). CONCLUSION: RAIT remains a safe option for the treatment of benign and TG. The experienced ARs are mainly mild to moderate in severity and mostly short-lived. As larger doses of radioactive iodine for WDTC and TG were more commonly associated with ARs, our study suggests that these patients merit stronger prophylactic measures as well as closer monitoring for earlier detection and management of these reactions.