Background Tuberculous meningitis (TBM) is the most severe form of TB. We prospectively documented the treatment outcomes and the risk factors for death in children with TBM from Kandahar, Afghanistan. Methods This prospective observational cohort study was conducted from February 2017 to January 2020 in hospitalised TBM children. All the patients were prospectively followed up for 12 mo. Data were analysed by using descriptive statistics, χ2 and multivariate logistic regression. Results A total of 818 TBM hospitalised patients with median age 4.8 (0.8–14.5) y were recruited. Females accounted for 60.9% (498/818). Upon admission 53.9% (n=441) and 15.2% (n=124) had TBM stages II and III, respectively, and 23.2% (n=190) had focal neurological signs. The case fatality rate was 20.2% (160/794) and 30.6% (243/794) survived with neurological sequelae. Independent risk factors for death were being unvaccinated for BCG (adjusted OR [AOR] 3.8, 95% CI 1.8 to 8.1), not receiving dexamethasone (AOR 2.5, 95% CI 1.5 to 4.2), being male (AOR 2.3, 95% CI 1.5 to 3.6), history of recent weight loss (AOR 2.2, 95% CI 1.3 to 3.9) and having stage III TBM (AOR 2.0, 95% CI 1.2 to 3.3). Conclusions TBM continues to cause high morbidity and mortality in Afghan children. Strategies to reduce mortality should emphasise early diagnosis and treatment, routine use of dexamethasone and increased BCG vaccination.
Background Recently, screening of colorectal cancer (CRC) patients for mismatch repair/microsatellite instability (MMR/MSI) status is widely practiced due to its potential predictive and prognostic roles and a screening tool to reveal Lynch Syndrome (LS). The purpose of the study was to evaluate concordance between immunohistochemistry (IHC) and MSI analysis methods for detection of MMR/MSI status in colorectal cancer patients in Kuantan, Pahang. Methods Fifty selected CRC cases of deficient mismatch repair (dMMR) and proficient mismatch repair (pMMR) which were identified immunohistochemically in the previous study were subjected to MSI analysis. MSI Analysis System 1.2 (Promega) was utilized. Results The results of MSI analysis method showed MSI-High: 26% (13/50), MSI-Low: 6% (3/50), and Microsatellite Stable: 68% (34/50). The concordance was perfect (0.896, Kappa value) between MSI analysis and IHC methods for the assessment of MMR/MSI status in CRC patients. The discordance was only 4% (2/50). MSI analysis identified all dMMR cases determined by IHC except one case. The obtained frequency of dMMR and pMMR patients was 11.4% (14/123) and 88.6% (109/123) by IHC method, respectively. Conclusion Our findings support the universal practice of evaluating the MMR/MSI status in all newly diagnosed CRC patients. Based on the perfect concordance of two methods, the method of choice is based on the availability of expertise and equipments. IHC is highly appreciable method due to its feasibility and reproducibility.
INTRODUCTION: The deficient mismatch repair (dMMR) status of colorectal cancer (CRC) is the hallmark of a defective DNA mismatch repair (MMR) system. Immunohistochemistry (IHC) indirectly detects the affected gene by the loss of its protein product. This study aimed to assess the frequency of different types of dMMR status and associate them with the clinicopathological characteristics of CRC patients diagnosed at Hospital Tengku Ampuan Afzan (HTAA) and the Sultan Ahmad Shah Medical Centre (SASMEC) using an immunohistochemical method. MATERIAL AND METHODS: Formalin-fixed paraffin-embedded (FFPE) tissue blocks of 123 CRC cases were retrieved from the Pathology Department of HTAA and SASMEC for patients diagnosed between 1 January 2017 and 31 December 2018. IHC was performed manually using an Envision Flex Polymer detection kit (Dako) along with four primary anti-mouse antibodies (MLH1, PMS2, MSH2, and MSH6) for the MMR proteins to assess dMMR status. RESULTS: Out of 123 cases, 21 (17.07%) showed the loss of one or more MMR protein expression and were dMMR. There was no statistically significant association between pMMR (proficient Mismatch repair) and dMMR cases with regards to clinicopathological factors (age, sex, race, site of the tumour, TNM (Tumour Node Metastasis) staging, bowel wall invasion, lymph node metastasis, lymphovascular invasion, histological type, and tumour differentiation). CONCLUSION: IHC is the preferred method and most reproducible test for assessing dMMR status in CRC patients in the histopathology diagnostic laboratory.
Introduction: Colorectal cancer is the third most common cancer worldwide. Microsatellite instability (MSI) contributes to be one of the main mechanisms in colorectal cancer. Individuals with MSI tumors have loss of expression of one or more Mismatch Repair proteins. MSI tumors have better survival rate than microsatellite stable (MSS) tumors, poor response to 5FU-based adjuvant chemotherapy and relatively successful immunotherapy in metastatic MSI tumors. Immunohistochemistry recognizes altered gene by recognizing loss of its protein product. Based on the presence or absence of Mismatch repair proteins, groups are classified into Mismatch repair proficient (MMR-p) and Mismatch repair deficient (MMR-d). Aim: To investigate the immunohistochemical profile of Mismatch repair proteins namely: hMLH1, hMSH2, hMSH6, and hPMS2 in surgically resected colorectal cancer specimens. Materials and Method: A total of 76 cases were selected from the Histopathology Department of HTAA to determine MMR protein expression status. Cases were either MMR-p or MMR-d. Results: Of the specimens which were properly immunostained, seventeen out of seventy-six cases (22.37%) showed loss of one or more MMR proteins expression and thus were MMR-d. MLH1, MSH2, MSH6 and PMS2 protein expression was detected as 85.53% (65/76), 81.6% (62/76), 88.16% (67/76), and 76.32% (58/76), respectively. Conclusion: Mismatch repair proteins profile should be done using immunohistochemistry in local laboratories on these selected cases before referring for the expensive molecular test.
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