AI-assisted biparametric MRI surveillance of prostate cancer: feasibility study.

OBJECTIVES: To evaluate the feasibility of automatic longitudinal analysis of consecutive biparametric MRI (bpMRI) scans to detect clinically significant (cs) prostate cancer (PCa). METHODS: This retrospective study included a multi-center dataset of 1513 patients who underwent bpMRI (T2 + DWI) between 2014 and 2020, of whom 73 patients underwent at least two consecutive bpMRI scans and repeat biopsies. A deep learning PCa detection model was developed to produce a heatmap of all PIRADS ≥ 2 lesions across prior and current studies. The heatmaps for each patient's prior and current examination were used to extract differential volumetric and likelihood features reflecting explainable changes between examinations. A machine learning classifier was trained to predict from these features csPCa (ISUP > 1) at the current examination according to biopsy. A classifier trained on the current study only was developed for comparison. An extended classifier was developed to incorporate clinical parameters (PSA, PSA density, and age). The cross-validated diagnostic accuracies were compared using ROC analysis. The diagnostic performance of the best model was compared to the radiologist scores. RESULTS: The model including prior and current study (AUC 0.81, CI: 0.69, 0.91) resulted in a higher (p = 0.04) diagnostic accuracy than the current only model (AUC 0.73, CI: 0.61, 0.84). Adding clinical variables further improved diagnostic performance (AUC 0.86, CI: 0.77, 0.93). The diagnostic performance of the surveillance AI model was significantly better (p = 0.02) than of radiologists (AUC 0.69, CI: 0.54, 0.81). CONCLUSIONS: Our proposed AI-assisted surveillance of prostate MRI can pick up explainable, diagnostically relevant changes with promising diagnostic accuracy. KEY POINTS: • Sequential prostate MRI scans can be automatically evaluated using a hybrid deep learning and machine learning approach. • The diagnostic accuracy of our csPCa detection AI model improved by including clinical parameters.

Quantitative CT perfusion imaging in patients with pancreatic cancer: a systematic review.

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death with a 5-year survival rate of 10%. Quantitative CT perfusion (CTP) can provide additional diagnostic information compared to the limited accuracy of the current standard, contrast-enhanced CT (CECT). This systematic review evaluates CTP for diagnosis, grading, and treatment assessment of PDAC. The secondary goal is to provide an overview of scan protocols and perfusion models used for CTP in PDAC. The search strategy combined synonyms for 'CTP' and 'PDAC.' Pubmed, Embase, and Web of Science were systematically searched from January 2000 to December 2020 for studies using CTP to evaluate PDAC. The risk of bias was assessed using QUADAS-2. 607 abstracts were screened, of which 29 were selected for full-text eligibility. 21 studies were included in the final analysis with a total of 760 patients. All studies comparing PDAC with non-tumorous parenchyma found significant CTP-based differences in blood flow (BF) and blood volume (BV). Two studies found significant differences between pathological grades. Two other studies showed that BF could predict neoadjuvant treatment response. A wide variety in kinetic models and acquisition protocol was found among included studies. Quantitative CTP shows a potential benefit in PDAC diagnosis and can serve as a tool for pathological grading and treatment assessment; however, clinical evidence is still limited. To improve clinical use, standardized acquisition and reconstruction parameters are necessary for interchangeability of the perfusion parameters.

Interactive 3D U-net for the segmentation of the pancreas in computed tomography scans.

The increasing incidence of pancreatic cancer will make it the second deadliest cancer in 2030. Imaging based early diagnosis and image guided treatment are emerging potential solutions. Artificial intelligence (AI) can help provide and improve widespread diagnostic expertise and accurate interventional image interpretation. Accurate segmentation of the pancreas is essential to create annotated data sets to train AI, and for computer assisted interventional guidance. Automated deep learning segmentation performance in pancreas computed tomography (CT) imaging is low due to poor grey value contrast and complex anatomy. A good solution seemed a recent interactive deep learning segmentation framework for brain CT that helped strongly improve initial automated segmentation with minimal user input. This method yielded no satisfactory results for pancreas CT, possibly due to a sub-optimal neural network architecture. We hypothesize that a state-of-the-art U-net neural network architecture is better because it can produce a better initial segmentation and is likely to be extended to work in a similar interactive approach. We implemented the existing interactive method, iFCN, and developed an interactive version of U-net method we call iUnet. The iUnet is fully trained to produce the best possible initial segmentation. In interactive mode it is additionally trained on a partial set of layers on user generated scribbles. We compare initial segmentation performance of iFCN and iUnet on a 100CT dataset using dice similarity coefficient analysis. Secondly, we assessed the performance gain in interactive use with three observers on segmentation quality and time. Average automated baseline performance was 78% (iUnet) versus 72% (FCN). Manual and semi-automatic segmentation performance was: 87% in 15 min. for manual, and 86% in 8 min. for iUNet. We conclude that iUnet provides a better baseline than iFCN and can reach expert manual performance significantly faster than manual segmentation in case of pancreas CT. Our novel iUnet architecture is modality and organ agnostic and can be a potential novel solution for semi-automatic medical imaging segmentation in general.

Biological control of Meloidogyne spp. in glasshouse-grown chrysanthemum.

Root-knot nematodes (Meloidogyne spp.) are a major problem in soil-based glasshouse-grown chrysanthemums. To combat root-knot nematodes in the glasshouse, the soil is typically steamed every 5-6 production cycles. However, this method is expensive, environmentally unfriendly and reduces resistance and resilience of the soil against pathogens and pests. Here, we added biological pesticides/a basic substance and biostimulants both individually and in combination to determine individual or interactive effects against damage by root-knot nematodes in chrysanthemums. We found that the application of biological nematicides derived from garlic extract, the basic substance chitosan HCl and biostimulants comprised of sea minerals and plant oils correlated with reduced root-knot nematode damage. These effects may have been due to direct effects against the nematodes or through indirect effects such as increased resistance and resilience of the plants. Overall, the biostimulants increased the total number of free-living nematodes in the soil, which could lead to a beneficial increase in nutrient cycling in the soils. Our results demonstrate that biological reagents show promise in reducing root-knot nematode damage in glasshouse-grown chrysanthemum and may lead to more resistance and resilient soils.

Cognitive decline after major oncological surgery in the elderly.

BACKGROUND: Elderly patients undergoing oncological surgery experience postoperative cognitive decline. The aims of this study were to examine the incidence of cognitive decline 3 months after surgery and identify potential patient-, disease- and surgery-related risk factors for postoperative cognitive decline in onco-geriatric patients. METHODS: A consecutive series of elderly patients (≥65 years) undergoing surgery for the removal of a solid tumour were included (n = 307). Cognitive performance was assessed pre-operatively and 3 months postoperatively. Postoperative decline was defined as a decline in scores of cognitive tests of ≥25% on ≥2 of 5 tests. RESULTS: Of the patients who had completed the assessments, 117 (53%, 95% confidence interval [CI]: 47-60) had improved cognitive test scores, whereas 26 (12%, 95% CI: 7.6-16) showed cognitive decline at 3 months postoperatively. In patients aged >75 years, the incidence of overall cognitive decline 3 months postoperatively was 18% (95% CI: 9.3-27). In patients with lower pre-operative Mini-Mental State Examination (MMSE) score (≤26) the incidence was 37% (95% CI: 18-57), and in patients undergoing major surgery it was 18% (95% CI: 10.6-26). Of the cognitive domains, executive function was the most vulnerable to decline. CONCLUSION: About half of the elderly patients show improvement in postoperative cognitive performance after oncological surgery, whereas 12% show cognitive decline. Advanced age, lower pre-operative MMSE score and major surgery are risk factors for cognitive decline at 3 months postoperatively and should be taken into account in the clinical decision-making progress. Research to develop interventions to preserve quality of life should focus on this high-risk subpopulation.

Asymmetric dimethylarginine and symmetric dimethylarginine prospectively relates to carotid wall thickening in black men: the SABPA study.

The relationship of both asymmetric (ADMA) and symmetric (SDMA) dimethylarginine with carotid wall thickness is inconclusive especially among black populations. We aimed to compare carotid intima media thickness (cIMT) and dimethylarginine levels in 75 black and 91 white men at baseline and after a 3-year follow-up, and to investigate associations of percentage change in cIMT with percentage change in dimethylarginine levels (ADMA and SDMA). Plasma levels of ADMA and SDMA were determined with a liquid chromatography mass spectrometry method and B-mode ultrasonography was used to determine the cIMT at baseline and follow-up. In black men, mean cIMT (p = 0.79) and ADMA levels (p = 0.67) remained the same, but SDMA levels were lower (p < 0.001) when comparing baseline and follow-up. In white men, cIMT increased (p < 0.001), but both mean ADMA and SDMA levels decreased (p < 0.001) over time. In black men, percentage change in cIMT was positively associated with percentage change in ADMA (R 2 = 0.49; ß = 0.46; p < 0.001) and percentage change in SDMA (R 2 = 0.46; ß = 0.41; p < 0.001). These associations were absent in the white men. Despite lower mean SDMA and similar ADMA and cIMT in black men, percentage change in cIMT was independently associated with percentage change in ADMA and percentage change in SDMA. These results suggest an important role for ADMA and SDMA lowering strategies to delay carotid wall thickening, especially in black populations prone to the development of cardiovascular disease.

Three-year change in endothelin-1 and markers of vascular remodelling in a bi-ethnic South African cohort: the SABPA study.

South Africans are at high risk for developing cardiovascular disease. Endothelin-1 is known for its vasoconstrictive properties and its ability to contribute to vascular structural changes. In this study we investigated the association of change in endothelin-1 levels and change in markers implicated in vascular remodelling after 3 years. Serum endothelin-1 levels and markers of vascular remodelling such as carotid intima-media thickness, carotid cross-sectional wall area (CSWA) and arterial compliance were measured. Participants were divided into two groups according to an increase (n=185) and a decrease (n=152) in plasma endothelin-1 levels after 3 years. In partial regression analysis, the extent of endothelin-1 increase correlated positively with a change in pulse pressure and inversely with the change in arterial compliance in the group with increased endothelin-1 levels after 3 years. In the group with decreased endothelin-1 levels, the extent of decreased endothelin-1 correlated inversely with a change in CSWA. In multiple regression analysis, after splitting for race, the increase in endothelin-1 levels associated positively with the change in pulse pressure (Adj. R2=0.092; ß=0.278; P=0.036) in the black participants only. In conclusion, with increased endothelin-1 levels after 3 years, the positive association between endothelin-1 and pulse pressure suggest subclinical haemodynamic changes with potential premature onset of cardiovascular disease in the black participants.

Recent advances in understanding hypertension development in sub-Saharan Africa.

Consistent reports indicate that hypertension is a particularly common finding in black populations. Hypertension occurs at younger ages and is often more severe in terms of blood pressure levels and organ damage than in whites, resulting in a higher incidence of cardiovascular disease and mortality. This review provides an outline of recent advances in the pathophysiological understanding of blood pressure elevation and the consequences thereof in black populations in Africa. This is set against the backdrop of populations undergoing demanding and rapid demographic transition, where infection with the human immunodeficiency virus predominates, and where under and over-nutrition coexist. Collectively, recent findings from Africa illustrate an increased lifetime risk to hypertension from foetal life onwards. From young ages black populations display early endothelial dysfunction, increased vascular tone and reactivity, microvascular structural adaptions as well as increased aortic stiffness resulting in elevated central and brachial blood pressures during the day and night, when compared to whites. Together with knowledge on the contributions of sympathetic activation and abnormal renal sodium handling, these pathophysiological adaptations result in subclinical and clinical organ damage at younger ages. This overall enhanced understanding on the determinants of blood pressure elevation in blacks encourages (a) novel approaches to assess and manage hypertension in Africa better, (b) further scientific discovery to develop more effective prevention and treatment strategies and

Quantification of systemic renin-angiotensin system peptides of hypertensive black and white African men established from the RAS-Fingerprint®.

OBJECTIVE: The objective of this study was to make use of a quantitative and qualitative approach comparing the systemic renin-angiotensin system (RAS) of hypertensive black and white African men by using RAS equilibrium analysis. MATERIALS AND METHODS: This sub-study involved 23 black (n = 15) and white (n = 8) hypertensive men aged 39.5-41 years, living in the North West Province of South Africa. The RAS-Fingerprinting was determined with LC-MS/MS quantification of angiotensin peptides. Blood pressure and other variables were determined with known methods. RESULTS: The main finding of this study was the significant lower Ang I (<5.0 and 45.1 pg/ml; p = 0.005) and Ang II (15.6 and 123.9 pg/ml; p ⩽ 0.001) encountered in the hypertensive black African men compared to their white counterparts. Levels of Ang 1-5 (downstream metabolite of Ang 1-7) (1.8 and 3.0 pg/ml), were detected in black and white hypertensive men, respectively. CONCLUSIONS: The observed differences between circulating RAS components, which are reflected via equilibrium angiotensin levels, point to a distinctive molecular regulation of the RAAS in the two study cohorts. The increased peripheral resistance observed in hypertensive black individuals might take over a dominant role in control of blood pressure in this study population. A novel highly sensitive LC-MS/MS method resolved the issue of peptide recovery variations during sample preparation by using internal standards for each individual angiotensin metabolite.

Leptin is positively associated with blood pressure in african men with a low body mass index: the SAfrEIC study.

Severe underweight may be a risk factor for hypertension in developing countries, although the manner whereby this occurs is unknown. Leptin is known to exert both beneficial and detrimental vascular effects, and is predictive of poor cardiovascular outcome at high levels, but also at low levels. We explored the relationship between blood pressure and leptin in black men from South Africa with a body mass index (BMI) in the underweight to normal range. We included 113 African men (BMI≤25 kg/m(2)) and took anthropometric, biochemical and cardiovascular measures. The blood pressure-leptin relationship was then investigated along quintiles of leptin and within BMI stratified median split (20 kg/m(2)) groups. Blood pressure increased across leptin quintiles 1-3 (p for trend≤0.040), whereas no relationship was observed along quintiles 3 to 5 (p for trend≥0.14) (adjusted for age and waist circumference). Blood pressure was similar in the two BMI median split groups (p≥0.083). In the low BMI group only, blood pressure associated positively with leptin following unadjusted, partial, and full adjustment (systolic blood pressure and diastolic blood pressure: R(2)=0.20-0.27, ß=0.32-0.34, p≤0.009). Decreasing leptin levels are not likely to contribute to hypertension prevalence in the underweight. Rather, in African men with a BMI≤20 kg/m(2), low leptin levels are positively and independently associated with elevated blood pressure, which is not seen at higher BMI (20-25 kg/m(2)). Our findings suggest a differential concentration dependent vascular effect of leptin in underweight and normal weight African men.

8-Oxo-7,8-dihydro-2'-deoxyguanosine, reactive oxygen species and ambulatory blood pressure in African and Caucasian men: the SABPA study.

Various studies indicate a relationship between increased oxidative stress and hypertension, resulting in increased DNA damage and consequent excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG). The aim of this study was to compare urinary 8-oxodG levels in African and Caucasian men and to investigate the association between ambulatory blood pressure (BP) and pulse pressure (PP) with 8-oxodG in these groups. We included 98 African and 92 Caucasian men in the study and determined their ambulatory BP and PP. Biochemical analyses included, urinary 8-oxodG, reactive oxygen species (ROS) (measured as serum peroxides), ferric reducing antioxidant power (FRAP), total glutathione (GSH), glutathione peroxidase (GPx) and glutathione reductase (GR) activity. The African men had significantly higher systolic (SBP) and diastolic blood pressure (DBP) (both p < 0.001). Assessment of the oxidative stress markers indicated significantly lower 8-oxodG levels (p < 0.001) in the African group. The African men also had significantly higher ROS (p = 0.002) with concomitant lower FRAP (p < 0.001), while their GSH levels (p = 0.013) and GR activity (p < 0.001) were significantly higher. Single and partial regression analyses indicated a negative association between urinary 8-oxodG levels with SBP, DBP and PP only in African men. These associations were confirmed in multiple regression analyses (SBP: R(2) = 0.41; ß = -0.25; p = 0.002, DBP: R(2) = 0.30; ß = -0.21; p = 0.022, PP: R(2) = 0.30; ß = -0.19; p = 0.03). Our results revealed significantly lower urinary 8-oxodG in African men, accompanied by a negative association with BP and PP. We propose that this may indicate a dose-response relationship in which increased oxidative stress may play a central role in the up-regulation of antioxidant defence and DNA repair mechanisms.

Cardiometabolic markers to identify cardiovascular disease risk in HIV-infected black South Africans.

BACKGROUND: The prevalence of HIV is the highest in sub-Saharan Africa; South Africa (SA) is one of the most affected countries with the highest number of adults living with HIV infection in the world. Besides the traditional risk factors for cardiovascular disease (CVD) in the general population, in people living with HIV there are specific factors - chronic inflammation, metabolic changes associated with the infection, therapy, and lipodystrophy - that potentially increase the risk for developing CVD. OBJECTIVE: This study proposes a screening discriminant model to identify the most important risk factors for the development of CVD in a cohort of 140 HIV-infected black Africans from the North West Province, SA. METHODS: Anthropometric measures, systolic blood pressure, diastolic blood pressure and the carotid-dorsalis pedis pulse wave velocity were determined. Blood was analysed to determine the levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, triglycerides (TGs) and glucose. Partial least squares discriminant analysis was performed as a supervised pattern recognition method. Independent Student's t-tests were further employed to compare the means of risk factors on interval scales; for comparison of categorical risk factors between groups, chi2 tests were used. RESULTS: A TG:HDL-C ratio > or = 1.49, TC:HDL-C ratio > or = 5.4 and an HDL-C level < or = 0.76 mmol/l indicated CVD risk in this cohort of patients living with HIV. CONCLUSION: The results have important health implications for black Africans living with HIV as these lipid levels may be a useful indicator of the risk for CVD.

Evaluation of waist-to-height ratio to predict 5 year cardiometabolic risk in sub-Saharan African adults.

BACKGROUND AND AIMS: Simple, low-cost central obesity measures may help identify individuals with increased cardiometabolic disease risk, although it is unclear which measures perform best in African adults. We aimed to: 1) cross-sectionally compare the accuracy of existing waist-to-height ratio (WHtR) and waist circumference (WC) thresholds to identify individuals with hypertension, pre-diabetes, or dyslipidaemia; 2) identify optimal WC and WHtR thresholds to detect CVD risk in this African population; and 3) assess which measure best predicts 5-year CVD risk. METHODS AND RESULTS: Black South Africans (577 men, 942 women, aged >30years) were recruited by random household selection from four North West Province communities. Demographic and anthropometric measures were taken. Recommended diagnostic thresholds (WC > 80 cm for women, >94 cm for men; WHtR > 0.5) were evaluated to predict blood pressure, fasting blood glucose, lipids, and glycated haemoglobin measured at baseline and 5 year follow up. Women were significantly more overweight than men at baseline (mean body mass index (BMI) women 27.3 ± 7.4 kg/m(2), men 20.9 ± 4.3 kg/m(2)); median WC women 81.9 cm (interquartile range 61-103), men 74.7 cm (63-87 cm), all P < 0.001). In women, both WC and WHtR significantly predicted all cardiometabolic risk factors after 5 years. In men, even after adjusting WC threshold based on ROC analysis, WHtR better predicted overall 5-year risk. Neither measure predicted hypertension in men. CONCLUSIONS: The WHtR threshold of >0.5 appears to be more consistently supported and may provide a better predictor of future cardiometabolic risk in sub-Saharan Africa.

Compromised bioavailable IGF-1 of black men relates favourably to ambulatory blood pressure: The SABPA study.

OBJECTIVES: Insulin-like growth factor-1 (IGF-1) has potent endothelial-protective, anti-platelet and anti-thrombotic activities, and also exerts mitogenic and proliferatory actions on vascular smooth muscle cells. Conflicting reports exist regarding the role of IGF-1 in vascular protection and atherogenesis. We therefore investigated the relationships of ambulatory blood pressure (BP) and carotid intima-media thickness (cIMT) with a range of components of the IGF-1 axis in a bi-ethnic population. METHODS: We included black (N = 86) and white (N = 101) men and measured growth hormone, total IGF-1, insulin-like growth factor binding protein-3 (IGFBP-3), and pregnancy-associated plasma protein-A (PAPP-A) levels. RESULTS: Ambulatory BP was almost 10 mmHg higher in black men (137/88 mmHg versus 128/80 mmHg; both p < 0.001), accompanied by an adverse profile of the IGF-axis for all measured components (all p < 0.01), including reduced bioavailable IGF-1 (IGF-1/IGFBP-3; p = 0.006) and tissue IGF-1 accessibility index as represented by IGF-1.PAPP-A/IGFBP-3 (p < 0.001). Single, partial and multiple regression analyses confirmed an independent inverse association between ambulatory systolic BP and bioavailable IGF-1 in black men (R(2) = 0.24; ß = -0.22; p = 0.035). cIMT was similar in the ethnic groups (p = 0.34), and was negatively associated with bioavailable IGF-1 in white men (R(2) = 0.42; ß = -0.17; p = 0.039) prior to adjustment for γ-glutamyl transferase (R(2) = 0.45; ß = -0.10; p = 0.25). CONCLUSION: Ambulatory systolic BP is inversely related to bioavailable IGF-1 in black men who displayed low IGF-1 concentrations. An inverse relation was found between cIMT and IGF-1 in white men, which disappeared after correction for γ-glutamyl transferase - opposing reports of a detrimental role of IGF-1 in the early stages of atherogenesis.

Chronic distress and acute vascular stress responses associated with ambulatory blood pressure in low-testosterone African men: the SABPA Study.

It is known that low testosterone (T) and high cortisol levels are associated with hypertension as well as with chronic stress, linking stress with elevated blood pressure (BP). However, the association between acute stress-, chronic stress responses and BP is not clear in Africans. Therefore, we examined the association between cortisol, psychological distress and BP responses in low- and high-T male subgroups. Beat-to-beat and ambulatory blood pressure (ABPM) and electrocardiogram measures were obtained. Serum samples were collected and analyzed for sex hormones and cortisol. Chronic psychological distress was verified with the General Health Questionnaire and acute stress with the cold pressor test. More chronic psychological distress was observed in both low- and high-T Africans compared with the Caucasians. The low-T Africans tended to have more ischemic events (P=0.06) and ABPM values (P⩽0.01) than any of the other groups. Both chronic distress (cortisol) and acute stress (total peripheral resistance cold pressor responses) were associated with ABPM in the low-T African group. Acute and chronic stress may contribute to increased BP in low-T African men. Their cortisol and vascular responses supported a tendency for ischemia, increasing their risk for coronary artery disease.

The link between vascular deterioration and branched chain amino acids in a population with high glycated haemoglobin: the SABPA study.

Globally the prevalence of non-communicable diseases, such as hypertension and type 2 diabetes, are escalating. Metabolomic studies indicated that circulating branched chain amino acids (BCAAs) are associated with insulin resistance, coronary artery disease and increased risk for cardiovascular events. We aimed to extend the current understanding of the cardiovascular risk associated with BCAAs. We explored whether BCAAs are related to markers of cardiovascular disease in a bi-ethnic population and whether this relationship was influenced by chronic hyperglycaemia. We included 200 African and 209 Caucasian participants, and determined their ambulatory blood pressure and carotid intima-media thickness (cIMT). We analysed blood samples for glycated haemoglobin (HbA1c) and BCAAs. Participants were stratified into two groups according to their HbA1c value using the median cut-off value of 5.6%. Ambulatory BP, cIMT and BCAAs were significantly higher (all p < 0.001) in the high HbA1c group. Single regression analyses indicated significant positive associations of ambulatory blood pressure and cIMT with BCAAs (all p < 0.05) in both the groups. These associations between ambulatory systolic blood pressure (SBP) (r = 0.16, p = 0.035) and cIMT (r = 0.22, p = 0.004) with BCAAs remained in the high HbA1c group after adjusting for age, gender, ethnicity and body mass index (BMI) and were confirmed in multiple regression analyses (ambulatory SBP: R (2) = 0.17, ß = 0.21, p = 0.005 and cIMT: R (2) = 0.30, ß = 0.19, p = 0.003). Our results demonstrate that BCAAs are independently related to ambulatory BP and cIMT in individuals with high HbA1c levels and suggest that potential cardiovascular deterioration accompany the rise in BCAAs in conditions of hyperglycaemia.

A comparison of the association between glomerular filtration and L-arginine status in HIV-infected and uninfected African men: the SAfrEIC study.

Hypertension, a major risk factor for cardiovascular disease worldwide, is increasing significantly in urbanised South Africans. Impaired glomerular filtration is a potential contributor to hypertension. Although HIV infection is widespread, little is known regarding its contribution to diminished estimated glomerular filtration rate (eGFR) and, in turn, hypertension in Africans. We compared eGFRs and cardiovascular profiles of newly identified HIV infected African men (N=53) not yet undergoing anti-retroviral therapy, and uninfected African men of similar age and anthropometry. The aim of the study was to determine whether eGFR is diminished in treatment naive HIV infected individuals and whether eGFR is associated with a potential modulator of hypertension, namely serum L-arginine. Cardiovascular risk factor profiles of HIV infected and uninfected men were similar. In men with healthy eGFRs >90 ml min(-1) per 1.73 m(2), eGFR was significantly lower with HIV infection (114 (90; 147)) compared with that in uninfected men: (120 (91; 168)), P=0.043. Despite the absence of clinically-diagnosed renal dysfunction, eGFR associated significantly with serum L-arginine only in HIV infected men (R(2)=0.277, ß=-0.299, P=0.034), whereas L-arginine did not stay in the model for uninfected men. This difference suggests that the fate of L-arginine as a substrate for nitric oxide generation may be altered in HIV infected individuals. Subsequently this is likely to escalate endothelial dysfunction, contributing to later hypertension and cardiovascular disease. Our findings show that while glomerular filtration rate is not associated with L-arginine in uninfected men, it is diminished and significantly negatively associated with serum L-arginine in HIV infected men.

Alkaline phosphatase and arterial structure and function in hypertensive African men: the SABPA study.

BACKGROUND: Vascular calcification is believed to be due to the conversion of vascular smooth muscle cells into osteoblast-like cells and is associated with mortality. Since hypertension and related mortality in Africans is a concern, we investigated associations between a marker of osteoblastic activity, alkaline phosphatase (ALP), and measures of arterial structure and function in hypertensive African men. METHODS: This study included 79 participants. We conducted 24h ambulatory blood pressure and carotid intima-media thickness (cIMT) measurements. cIMT was obtained with an intra-observer variability of 0.04 mm and the cross-sectional wall area (CSWA) was calculated. ALP was measured in serum. RESULTS: ALP was within its reference range (101.6 vs. 30.0-120.0 U/L), however cIMT was higher when this group was stratified and compared to gender and age-specific reference values. In univariate and partial regressions, and confirmed with multiple regression analyses, 24h systolic blood pressure (ß=0.289, p=0.018), 24h pulse pressure (ß=0.387, p=0.002), but not 24h diastolic blood pressure (ß=0.073, p=0.58), were positively associated with ALP. In addition, mean cIMT (ß=0.322, p=0.006) and CSWA (ß=0.285, p=0.013) also correlated positively with ALP after adjusting for significant covariates, and after excluding participants with diabetes, renal dysfunction or a HIV positive status. CONCLUSION: Serum alkaline phosphatase is adversely associated with measures of arterial structure and function in hypertensive African men.

Imaging vascular function for early stage clinical trials using dynamic contrast-enhanced magnetic resonance imaging.

Many therapeutic approaches to cancer affect the tumour vasculature, either indirectly or as a direct target. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has become an important means of investigating this action, both pre-clinically and in early stage clinical trials. For such trials, it is essential that the measurement process (i.e. image acquisition and analysis) can be performed effectively and with consistency among contributing centres. As the technique continues to develop in order to provide potential improvements in sensitivity and physiological relevance, there is considerable scope for between-centre variation in techniques. A workshop was convened by the Imaging Committee of the Experimental Cancer Medicine Centres (ECMC) to review the current status of DCE-MRI and to provide recommendations on how the technique can best be used for early stage trials. This review and the consequent recommendations are summarised here. Key Points • Tumour vascular function is key to tumour development and treatment • Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can assess tumour vascular function • Thus DCE-MRI with pharmacokinetic models can assess novel treatments • Many recent developments are advancing the accuracy of and information from DCE-MRI • Establishing common methodology across multiple centres is challenging and requires accepted guidelines.

Automatic computer-aided detection of prostate cancer based on multiparametric magnetic resonance image analysis.

In this paper, a fully automatic computer-aided detection (CAD) method is proposed for the detection of prostate cancer. The CAD method consists of multiple sequential steps in order to detect locations that are suspicious for prostate cancer. In the initial stage, a voxel classification is performed using a Hessian-based blob detection algorithm at multiple scales on an apparent diffusion coefficient map. Next, a parametric multi-object segmentation method is applied and the resulting segmentation is used as a mask to restrict the candidate detection to the prostate. The remaining candidates are characterized by performing histogram analysis on multiparametric MR images. The resulting feature set is summarized into a malignancy likelihood by a supervised classifier in a two-stage classification approach. The detection performance for prostate cancer was tested on a screening population of 200 consecutive patients and evaluated using the free response operating characteristic methodology. The results show that the CAD method obtained sensitivities of 0.41, 0.65 and 0.74 at false positive (FP) levels of 1, 3 and 5 per patient, respectively. In conclusion, this study showed that it is feasible to automatically detect prostate cancer at a FP rate lower than systematic biopsy. The CAD method may assist the radiologist to detect prostate cancer locations and could potentially guide biopsy towards the most aggressive part of the tumour.