Inflammation and angiogenesis are hypothesized to be important factors contributing to plaque vulnerability, whereas calcification is suggested to confer stability. To investigate this in vivo, we ...combined CT angiography and PET and compared the findings with immunohistochemistry for patients undergoing carotid endarterectomy. Methods: Twenty-one consecutive patients (18 men, 3 women; mean age ± SD, 68.3 ± 7.3) undergoing carotid endarterectomy were recruited for combined carotid ^sup 18^F-FDG PET/CT angiography. Plaque ^sup 18^F-FDG uptake was quantified with maximum standardized uptake value, and CT angiography quantified percentage plaque composition (calcium and lipid). Surgical specimens underwent ex vivo CT aiding image registration, followed by immunohistochemical staining for CD68 (macrophage density) and vascular endothelial growth factor (angiogenesis). Relationships between imaging and immunohistochemistry were assessed with Spearman rank correlation and multivariable regression. Results: The mean (±SD) surgically excised carotid plaque ^sup 18^F-FDG metabolism was 2.4 (±0.5) versus 2.2 (±0.3) contralaterally (P = 0.027). There were positive correlations between plaque ^sup 18^F-FDG metabolism and immunohistochemistry with CD68 (ρ = 0.55; P = 0.011) and vascular endothelial growth factor (ρ = 0.47; P = 0.031). There was an inverse relationship between plaque ^sup 18^F-FDG metabolism and plaque percentage calcium composition on CT (ρ = -0.51; P = 0.018) and between calcium composition and immunohistochemistry with CD68 (ρ = -0.57; P = 0.007). Regression showed that maximum standardized uptake value and calcium composition were independently significant predictors of angiogenesis, and calcium composition was a predictor of macrophage density. Conclusion: We provide in vivo evidence that increased plaque metabolism is associated with increased biomarkers of angiogenesis and inflammation, whereas plaque calcification is inversely related to PET and histologic biomarkers of inflammation. PUBLICATION ABSTRACT
Abstract only Introduction Abdominal aortic aneurysm (AAA) is a common disease that predisposes to aortic rupture, which has a high mortality. The only intervention that is proven to reduce rupture ...is invasive surgery. Understanding causal disease pathways may allow development of non-surgical therapies to target AAA formation, progression or rupture. In this study we investigate the role of interleukin-6 and AAA. Methods We performed systematic review and meta-analysis of the published literature in order to determine the association between circulating interleukin-6 (IL-6) and presence of AAA. We then investigated the association between a common non-synonymous variant in the interleukin-6 receptor gene (IL6R) and presence of AAA, performed in vitro functional analyses of this variant, and expression studies in aortic tissue. Results Meta-analysis of seven case-control studies of AAA (infra-renal aortic diameter ≥ 3cm), pooling data from 869 cases and 851 controls demonstrated consistently higher levels of circulating IL-6 in AAA compared to controls (standardised mean difference (SMD) = 0.42 units, 95% CI = 0.32-0.52, I2 = 69.4%, P for fixed effects = 1.29 x 10-16, P for random effects = 1.2 x10-5). There was less heterogeneity when comparing large AAA (>5cm, n = 547), to disease free controls (n = 712) (SMD = 0.46 units, 95% CI 0.34-0.57, I2=31.5, P = 2.2 x 10-14). The rare allele of rs7529229, which tags the non-synonymous variant (p.Asp358Ala, rs2228154) was consistently associated with reduced risk of AAA in meta-analysis of 4 studies, pooling data from 4,708 cases and 15,816 (per allele odds ratio 0.84, 95% CI 0.80-0.89, P = 2.7 x 10-11, I2=0). This variant was also associated with reduced risk incident AAA endpoints (rupture +/- repair) in prospective analysis of 7,888 individuals with known arterial disease (hazard ratio = 0.81, 95% CI 0.67 - 0.99, P = 0.043). Expression studies revealed strong correlation between IL-6 expression target genes (STAT3, MYC, ATF3, BCL3 and ICAM1) in aortic adventitia. In vitro analyses demonstrate that in lymphoblastoid cells, there is a genotype specific reduction in expression of downstream mediators of IL-6 signalling in response to IL-6 stimulation. Conclusions These data indicate that signalling via the IL-6 receptor is likely to be causal in the development of AAA. This suggests that this pathway may represent a novel target for pharmacological treatment of AAA with biological agents such as Tocilizumab, and clinical trials to assess this may be warranted.
Inflammation and angiogenesis are hypothesized to be important factors contributing to plaque vulnerability, whereas calcification is suggested to confer stability. To investigate this in vivo, we ...combined CT angiography and PET and compared the findings with immunohistochemistry for patients undergoing carotid endarterectomy. METHODS: Twenty-one consecutive patients (18 men, 3 women; mean age plus or minus SD, 68.3 plus or minus 7.3) undergoing carotid endarterectomy were recruited for combined carotid 18F-FDG PET/CT angiography. Plaque 18F-FDG uptake was quantified with maximum standardized uptake value, and CT angiography quantified percentage plaque composition (calcium and lipid). Surgical specimens underwent ex vivo CT aiding image registration, followed by immunohistochemical staining for CD68 (macrophage density) and vascular endothelial growth factor (angiogenesis). Relationships between imaging and immunohistochemistry were assessed with Spearman rank correlation and multivariable regression. RESULTS: The mean ( plus or minus SD) surgically excised carotid plaque 18F-FDG metabolism was 2.4 ( plus or minus 0.5) versus 2.2 ( plus or minus 0.3) contralaterally (P = 0.027). There were positive correlations between plaque 18F-FDG metabolism and immunohistochemistry with CD68 ( rho = 0.55; P = 0.011) and vascular endothelial growth factor ( rho = 0.47; P = 0.031). There was an inverse relationship between plaque 18F-FDG metabolism and plaque percentage calcium composition on CT ( rho = -0.51; P = 0.018) and between calcium composition and immunohistochemistry with CD68 ( rho = -0.57; P = 0.007). Regression showed that maximum standardized uptake value and calcium composition were independently significant predictors of angiogenesis, and calcium composition was a predictor of macrophage density. CONCLUSION: We provide in vivo evidence that increased plaque metabolism is associated with increased biomarkers of angiogenesis and inflammation, whereas plaque calcification is inversely related to PET and histologic biomarkers of inflammation.
Background: Short inter-pregnancy interval (IPI) is a potential risk factor for adverse pregnancy outcomes. Previous reports from sub-Sahara Africa documented increasing incidence of short IPI but ...evidence is lacking in its effect on pregnancy outcome. Aim: The study aimed to determine the effect of short IPI on pregnancy outcome in Nigeria. Subjects and Methods: It was a prospective cohort study of 271 pregnant women receiving antenatal care in a tertiary hospital in Nigeria. For every eligible woman with short IPI (<18 months) recruited; a suitable control with IPI ≥18 months was selected. Statistical analysis was both inferential and descriptive using the statistical package for social sciences version 24 (SPSS Inc. Chicago, Illinois, USA) for windows. A P value of less than 0.05 was considered statistically significant. Results: Incidence of maternal anemia was higher in women with short IPI than control (RR: 2.091; 95% CI: 1.4433.031; P < 0.001). Other maternal and perinatal outcome measures including premature rupture of membranes, preterm labor/delivery, pregnancy induced hypertension, third trimester bleeding, postpartum hemorrhage, and inadequate gestational weight gain did not show any significant association with short IPI (P > 0.05). Conclusion: Short IPI is associated with anemia in pregnancy in Nigeria. Public health campaigns for improvement in uptake of family planning services and breastfeeding may help reduce the incidence of short IPI and anemia in low income countries.
Sickle cell anemia (SCA) is a hereditary blood disorder with global prevalence, including in Nigeria. Despite advancements in SCA care management, understanding the long-term impact on organs during ...steady state has remained inconclusive.
This study aimed to investigate the long-term changes in intra-abdominal organs of SCA children compared with non-SCA children during steady state using two-dimensional ultrasound assessment.
A total of 116 children (58 SCA and 58 controls) were enrolled between June 2021 and July 2022. Clinico-demographic data were collected through an interviewer-administered questionnaire. Two-dimensional ultrasound was used to measure the liver, spleen, kidneys, and inferior vena cava in all subjects. Age-matched controls had AA or AS genotypes.
Of the 58 patients with SCA, 65.5% were males with an overall mean age of 8.1 ± 3.4 years, while among the non-SCA cohort (n = 58), 48.3% were males with an overall mean age of 8.7 ± 3.9 years. There was no statistically significant difference in the age and gender distribution between the SCA and non-SCA cohorts (P = 0.390 and P = 0.091, respectively). SCA subjects had a larger mean hepatic size than non-SCA subjects (12.09 cm ± 2.23 vs. 11.67 cm ± 1.96; P = 0.276) but smaller mean splenic size (8.01 cm ± 1.89 vs. 8.19 cm ± 1.61; P = 0.577) and inferior vena cava diameter (1.16 cm ± 0.29 vs. 1.25 cm ± 0.33; P = 0.100). Left kidney length and breadth were significantly greater in SCA patients (8.91 ± 1.16 vs. 8.27 ± 1.30; P = 0.006 and 4.15 ± 0.92 vs. 3.79 ± 0.48; P = 0.008, respectively).
This study highlights the utility of two-dimensional ultrasound assessment in monitoring intra-abdominal organ changes in SCA children, suggesting its cost-effective benefits in monitoring health outcomes in SCA patients.
Routine viral load and CD4+ testing is key to monitoring the extent of danger caused by HIV and response to antiretroviral therapy (ART) for HIV individuals, but its availability has been limited in ...low and middle-income countries. The study sort to ascertain relationship between serum Human Growth Hormone (HGH) gold standard with CD4 cells and viral load in HIV-infected patients. CD4+ T-cells, HIV viral load, and HGH were assayed in HIV- infected patients from May to December 2020. 460 subjects were engaged and separated into two groups: the HIV-infected untreated (Pre-ART) and the control groups. An interventional study was conducted for the Pre-Art group after six months. Serum HGH was assayed by the ELISA method, CD4 cell count was examined by BD-FACScan flow cytometer, and HIV viral load was assessed using RT-PCR. The CD4 count and serum HGH of Pre-ART HIV-infected subjects were significantly low (p<0.05), while the viral load was significantly high compared to those treated with ART for 6months (p<0.05). CD4 count and serum HGH were significantly higher (p<0.05) in females than in males. It also reveals that CD4 count correlates positively with HGH level (r= 0.191**). Serum HGH could serve as a surrogate marker and valuable index in monitoring HIV patients.
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