IntroductionSickle Cell Disease (SCD) has a high mortality rate in the environment where we practice. There is lack of contemporal autopsy studies describing causes of death among SCD patients at our centre.MethodsThis is a retrospective study of SCD patients who died between January 1991 and December 2008 and that had autopsy examination to confirm the cause of death in a Nigerian teaching hospital. The clinical data, including the age, gender, Hb genotype, and the major autopsy findings and cause of death were obtained for each patient from the complete autopsy reports that included histopathological examination. Multiple causes of death were entertained.ResultsA total of 52 autopsies were performed. The mean age at death was 21.3 years (range, 1-47 years) and a male/female ratio of 1.3:1. HbS+C patients lived longer than HbS patients (21.0 years Vs 24.0 years) and peak mortality was in the 2nd and 3rd decades of life. The commonest causes of death as a single entity or in combination included infections in 78% of cases, fatal thrombotic/embolic events (37%) making acute chest syndrome a leading cause of death. This was followed closely by anemia alone or in combination with acute sequestration crises in 31% of patients.ConclusionInfections are the commonest causes of death in Nigerian SCD patients, efforts to reduce infection especially early in life through prophylaxis or vaccination will impact on the overall survival of these patients.

Recent advances in whole-slide imaging (WSI) technology have led to the development of a myriad of computer vision and artificial intelligence-based diagnostic, prognostic, and predictive algorithms. Computational Pathology (CPath) offers an integrated solution to utilise information embedded in pathology WSIs beyond what can be obtained through visual assessment. For automated analysis of WSIs and validation of machine learning (ML) models, annotations at the slide, tissue, and cellular levels are required. The annotation of important visual constructs in pathology images is an important component of CPath projects. Improper annotations can result in algorithms that are hard to interpret and can potentially produce inaccurate and inconsistent results. Despite the crucial role of annotations in CPath projects, there are no well-defined guidelines or best practices on how annotations should be carried out. In this paper, we address this shortcoming by presenting the experience and best practices acquired during the execution of a large-scale annotation exercise involving a multidisciplinary team of pathologists, ML experts, and researchers as part of the Pathology image data Lake for Analytics, Knowledge and Education (PathLAKE) consortium. We present a real-world case study along with examples of different types of annotations, diagnostic algorithm, annotation data dictionary, and annotation constructs. The analyses reported in this work highlight best practice recommendations that can be used as annotation guidelines over the lifecycle of a CPath project.

AimsWe sought to use PCR followed by high-resolution melting analysis to develop a single closed-tube screening panel to screen for Lynch syndrome. This comprises tests for microsatellite instability (MSI), MLH1 methylation promoter and BRAF mutation.MethodsFor MSI testing, five mononucleotide markers (BAT25, BAT26, BCAT25, MYB, EWSR1) were developed. In addition, primers were designed to interrogate Region C of the MLH1 promoter for methylation (using bisulphite-modified DNA) and to test for mutations in codon 600 of BRAF. Two separate cohorts from Nottingham (n=99, 46 with MSI, 53 being microsatellite stable (MSS)) and Edinburgh (n=88, 45 MSI, 43 MSS) were tested.ResultsAll the cases (n=187) were blind tested for MSI and all were correctly characterised by our panel. The MLH1 promoter and BRAF were tested only in the Nottingham cohort. Successful blinded analysis was performed on the MLH1 promoter in 97 cases. All MSS cases showed a pattern of non-methylation while 41/44 cases with MSI showed full methylation. The three cases with MSI and a non-methylated pattern had aberrations in MSH2 and MSH6 expression. BRAF mutation was detected in 61% of MSI cases and 11% of MSS cases.Finally, 12 cases were blind screened by using the whole panel as a single test. Of these, five were identified as MSS, four as MSI/non-LS and three as MSI/possible LS. These results were concordant with the previous data.ConclusionWe describe the Nottingham Lynch Syndrome Test (N_LyST). This is a quick, simple and cheap method for screening for Lynch syndrome.

The prevalent form of thyroid diseases seen at Olabisi Onabanjo University Teaching Hospital was simple goitre and most common in females. Studies on autoimmunity and other goitrogens are required to further elucidate the cause of this high prevalence.

Objective The osteoporosis in thyroid disorder has the lowest report especially in sub-Saharan Africa. This study aims to determine the prevalence, predictive factors, and characteristics of osteoporosis in hyperthyroid patients. Method Forty (40) hyperthyroid patients and healthy controls ages 21–50 years were recruited in this study. Questionnaires were administered to capture bio- and clinical data. Biochemical tests included blood, thyroid functions, intact parathyroid hormone, corrected calcium, and 25-hydroxyvitamin D tests. Bone mineral density (BMD) was also evaluated. Data were analyzed using the SPSS 21. A p value < 0.05 was regarded as significant. Results Osteoporosis was observed in 18 (45%) of study subjects, 13 (72.2%) females and 5 (27.8%) males, respectively. The BMD of the hyperthyroid patients had a negative correlation with free triiodothyronine, FT3 (r = −0.49, p = 0.005), FT4 (r = −0.33, p = 0.009), corrected calcium (r = −0.31, p = 0.039), alkaline phosphatase (r = −0.53, p < 0.001), and osteocalcin (r = −0.61, p < 0.001). Conversely, a positive association with thyroid-stimulating hormone (TSH) (r = 0.54, p < 0.001) was observed. Multiple regression showed osteocalcin (p < 0.001) and TSH (p = 0.015) as independent predictors of osteoporosis. Conclusion Thyrotoxicosis is a risk factor for osteoporosis occurrence, and we recommend routine screening for this bone disease in persons over 20 years old with this disorder.

Aim:The most recent study on the clinicopathological features of gastric carcinoma from the University College Hospital (UCH), Ibadan, was done in 2000. The aim of this study is to update the knowledge on the clinicopathological features of gastric carcinoma diagnosed in the Pathology Department of the UCH Ibadan between 2000 and 2011.Materials and Methods:This was a 12-year retrospective review of clinical and demographic data and the histopathological features of gastric cancers diagnosed at the Pathology Department of the UCH. The chi square test, Fisher's exact test, and the t-independent test were used as applicable in the statistical analyses.Results:A total of 117 cases of gastric carcinoma were histologically diagnosed at the Pathology Department of UCH, Ibadan in this period giving a relative ratio frequency of 1.38% for all cancers. It represented 18.4% of all gastrointestinal tract malignancies diagnosed in the same period. There was a male preponderance with male:female ratio of 1.72:1; the middle-aged and elderly made up about 76.1% of cases. The disease was clinically and histologically advanced in 92.8% of cases. Gastric tumours were predominantly antral/ pyloric in 80% of cases and exophytic in 62.3% of cases. The intestinal histotype constituted 47.0% cases although a rise in the diffuse histological type was observed.Conclusion:There is a decline in the relative ratio frequency of gastric carcinoma in Ibadan; and a fall in the rate of the intestinal type of gastric carcinoma relative to the diffuse type when compared to previous studies from our centre.

The rate expression of CHEK1 is high in Nigerian breast cancer cases and is associated with an aggressive phenotype and poor prognosis.

Background: Disparities in DNA template quantity across sample wells is a common occurrence in PCR experiments and a frequent cause of bogus results in research and diagnostics. High Resolution Melt (HRM) analysis, a robust genotyping technique, was shown to be highly reproducible irrespective of the reaction volume and DNA template concentration used for PCR. The aim of this study is to determine if HRM can maintain its reproducibility/reliability when varying amounts of starting DNA templates are utilized for the upstream PCR. Methods: Serial dilutions of differentially prepared DNA templates were amplified and subjected to HRM analysis using the ABI 7500 Fast Real Time PCR machine and the ABI HRM software v2.0.6. The first serial dilution set consisted of seven 1:2 serial dilutions of amplicon-enriched DNA templates from two samples of known genotypes at exon 9 of PIK3CA, while the second serial dilution set consisted of four 1:10 dilutions of two different template types from the same sample: original FFPE DNA template and amplicon-enriched DNA template. Results: HRM analysis was reproducible across two-to one thousand-fold difference in starting DNA template in the upstream PCR, so long as the starting DNA template is of ample quality and quantity to give an adequate PCR amplification. Conclusions: HRM is highly reliable in the presence of a wide variation in the amount of starting template across wells for the upstream PCR, and the factor that determines HRM reproducibility is the adequacy of the PCR amplification. (Clin. Lab. 2015;61:xx-xx.