Derangements of immunological proteins in HIV-associated diffuse large B-cell lymphoma: the frequency and prognostic impact.

Introduction: Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy of B-cells frequently encountered among people living with HIV. Immunological abnormalities are common in immunocompetent individuals with DLBCL, and are often associated with poorer outcomes. Currently, data on derangements of immunological proteins, such as cytokines and acute phase reactants, and their impact on outcomes in HIV-associated DLBCL (HIV-DLBCL) is lacking. This study assessed the levels and prognostic relevance of interleukin (IL)-6, IL-10 and Transforming Growth Factor Beta (TGFß), the acute phase proteins C-reactive protein (CRP) and ferritin; serum free light chains (SFLC) (elevation of which reflects a prolonged pro-inflammatory state); and the activity of the immunosuppressive enzyme Indoleamine 2,3-dioxygenase (IDO)in South African patients with DLBCL. Methods: Seventy-six patients with incident DLBCL were enrolled, and peripheral blood IL-6, IL-10, TGFß, SFLC and IDO-activity measured in selected patients. Additional clinical and laboratory findings (including ferritin and CRP) were recorded from the hospital records. Results: Sixty-one (80.3%) of the included patients were people living with HIV (median CD4-count = 148 cells/ul), and survival rates were poor (12-month survival rate 30.0%). The majority of the immunological proteins, except for TGFß and ferritin, were significantly higher among the people living with HIV. Elevation of IL-6, SFLC and IDO-activity were not associated with survival in HIV-DLBCL, while raised IL-10, CRP, ferritin and TGFß were. On multivariate analysis, immunological proteins associated with survival independently from the International Prognostic Index (IPI) included TGFß, ferritin and IL-10. Conclusion: Derangements of immunological proteins are common in HIV-DLBCL, and have a differential association with survival compared to that reported elsewhere. Elevation of TGFß, IL-10 and ferritin were associated with survival independently from the IPI. In view of the poor survival rates in this cohort, investigation of the directed targeting of these cytokines would be of interest in our setting.

Underdiagnosis of iron deficiency anaemia in HIV-infected individuals: a pilot study using soluble transferrin receptors and intensive bone marrow iron stores to improve the diagnosis.

AIM: We compared soluble transferrin receptors (sTfR), serum ferritin, mean cell volume (MCV) of red cells and the sTfR-ferritin index with the intensive method bone marrow trephine (BMT) iron stores in the diagnosis of iron deficiency anaemia (IDA) in Human Immunodeficiency Virus (HIV)-positive hospitalised participants. METHODS: In this cross-sectional study, we recruited hospitalised HIV-positive and coronavirus of 2019 (COVID-19)-negative adults with anaemia who required a bone marrow examination as part of their diagnostic workup. We measured the full blood count, ferritin, sTfR and assessed iron using the intensive method in Haemotoxylin and Eosin (H&E)-stained BMT core biopsies of consenting participants. RESULTS: Of the 60 enrolled participants, 57 were evaluable. Thirteen (22.80%) had IDA on H&E BMT iron stores assessment, and 44 (77.19%) had anaemia of chronic diseases (ACD). The sTfR and the sTfR-ferritin index had sensitivities of 61.54% and 53.85%, respectively, for IDA diagnosis. The sensitivity and specificity of ferritin was 7.69% and 92.31%, respectively. The sTfR and sTfR-ferritin index's diagnostic specificity was relatively low at 46.15% and 38.46%, respectively. CONCLUSION: In this pilot study in HIV-positive participants, the prevalence of iron deficiency using the BMT assessment was low. Both the sTfR and the sTfR-ferritin index had a better quantitative correlation to bone marrow iron stores when compared with the MCV and ferritin and, may be more accurate surrogate markers of IDA.

Measurement of kidney function in Malawi, South Africa, and Uganda: a multicentre cohort study.

BACKGROUND: The burden of kidney disease in many African countries is unknown. Equations used to estimate kidney function from serum creatinine have limited regional validation. We sought to determine the most accurate way to measure kidney function and thus estimate the prevalence of impaired kidney function in African populations. METHODS: We measured serum creatinine, cystatin C, and glomerular filtration rate (GFR) using the slope-intercept method for iohexol plasma clearance (mGFR) in population cohorts from Malawi, Uganda, and South Africa. We compared performance of creatinine and cystatin C-based estimating equations to mGFR, modelled and validated a new creatinine-based equation, and developed a multiple imputation model trained on the mGFR sample using age, sex, and creatinine as the variables to predict the population prevalence of impaired kidney function in west, east, and southern Africa. FINDINGS: Of 3025 people who underwent measured GFR testing (Malawi n=1020, South Africa n=986, and Uganda n=1019), we analysed data for 2578 participants who had complete data and adequate quality measurements. Among 2578 included participants, creatinine-based equations overestimated kidney function compared with mGFR, worsened by use of ethnicity coefficients. The greatest bias occurred at low kidney function, such that the proportion with GFR of less than 60 mL/min per 1·73 m2 either directly measured or estimated by cystatin C was more than double that estimated from creatinine. A new creatinine-based equation did not outperform existing equations, and no equation, including the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 race-neutral equation, estimated GFR within plus or minus 30% of mGFR for 75% or more of the participants. Using a model to impute kidney function based on mGFR, the estimated prevalence of impaired kidney function was more than two-times higher than creatinine-based estimates in populations across six countries in Africa. INTERPRETATION: Estimating GFR using serum creatinine substantially underestimates the individual and population-level burden of impaired kidney function in Africa with implications for understanding disease progression and complications, clinical care, and service provision. Scalable and affordable ways to accurately identify impaired kidney function in Africa are urgently needed. FUNDING: The GSK Africa Non-Communicable Disease Open Lab. TRANSLATIONS: For the Luganda, Chichewa and Xitsonga translations of the abstract see Supplementary Materials section.

The Detection of Toxic Compounds in Extracts of Callilepis laureola (Oxeye Daisy) and Senecio latifolius (Ragwort) by Ultra-Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS/MS).

Methods used for the detection of toxic components of Callilepis laureola and Senecio latifolius have ranged from the use of thin-layer chromatography, spectrophotometry, and immunoassay to gas chromatography with mass spectrometry. However, each of these techniques has a number of drawbacks. In this chapter, we will describe a solid-phase extraction technique, which allows for the detection and quantitation of the toxins atractyloside and retrorsine in each plant extract using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). This methodology offers high specificity and sensitivity and the ability to identify a broad range of analytes.

Glucocorticoids associate with cardiometabolic risk factors in black South Africans.

Circulating glucocorticoids are associated with metabolic syndrome and related cardiometabolic risk factors in non-Africans. This study investigated these associations in Africans, whose metabolic phenotype reportedly differs from Europeans. Adiposity, blood pressure, glycaemia, insulin resistance, and lipid profile, were measured in 316 African men and 788 African women living in Soweto, Johannesburg. The 2009 harmonized criteria were used to define metabolic syndrome. Serum glucocorticoids were measured using liquid chromatography-mass spectrometry. Cortisol was associated with greater odds presenting with metabolic syndrome (odds ratio (95% CI) =1.50 (1.04, 2.17) and higher systolic (beta coefficient, ß (95% CI) =0.04 (0.01, 0.08)) and diastolic (0.05 (0.02, 0.09)) blood pressure, but higher HDL (0.10 (0.02, 0.19)) and lower LDL (-0.14 (-0.24, -0.03)) cholesterol concentrations, in the combined sample of men and women. In contrast, corticosterone was only associated with higher insulin sensitivity (Matsuda index; 0.22 (0.03, 0.41)), but this was not independent of BMI. Sex-specific associations were observed, such that both cortisol and corticosterone were associated with higher fasting glucose (standardized ß (95% CI): 0.24 (0.12, 0.36) for cortisol and 0.12 (0.01, 0.23) for corticosterone) and HbA1c (0.13 (0.01, 0.25) for cortisol and 0.12 (0.01, 0.24) for corticosterone) in men only, but lower HbA1c (0.10 (-0.20, -0.01) for cortisol and -0.09 (-0.18, -0.03) for corticosterone) in women only. Our study reports for the first time that associations between circulating glucocorticoid concentrations and key cardiometabolic risk factors exhibit both glucocorticoid- and sex-specificity in Africans.

Evaluating chronic kidney disease in rural South Africa: comparing estimated glomerular filtration rate using point-of-care creatinine to iohexol measured GFR.

OBJECTIVES: The prevalence of chronic kidney disease is rising rapidly in low- and middle-income countries. Serum creatinine and estimation of glomerular filtration rate (GFR) are critical diagnostic tools, yet access to centralised laboratory services remains limited in primary care resource-limited settings. The aim of this study was to evaluate point-of-care (POC) technologies for serum creatinine measurement and to compare their performance to a gold standard measurement using iohexol measured GFR (mGFR). METHODS: POC creatinine was measured using iSTAT® and StatSensor® devices in capillary and venous whole blood, and laboratory creatinine was measured using the compensated kinetic Jaffe method in 670 participants from a rural area in South Africa. GFR estimating equations Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease (CKD-EPI and MDRD) for POC and laboratory creatinine were compared to iohexol mGFR. RESULTS: Calculated GFR for laboratory and POC creatinine measurements overestimated GFR (positive bias of 1.9-34.1 mL/min/1.73 m2). However, all POC devices had less positive bias than the laboratory Jaffe method (1.9-14.7 vs. 34.1 for MDRD, and 8.4-19.9 vs. 28.6 for CKD-EPI). Accuracy within 30% of mGFR ranged from 0.56 to 0.72 for POC devices and from 0.36 to 0.43 for the laboratory Jaffe method. POC devices showed wider imprecision with coefficients of variation ranging from 4.6 to 10.2% compared to 3.5% for the laboratory Jaffe method. CONCLUSIONS: POC estimated GFR (eGFR) showed improved performance over laboratory Jaffe eGFR, however POC devices suffered from imprecision and large bias. The laboratory Jaffe method performed poorly, highlighting the need for laboratories to move to enzymatic methods to measure creatinine.

Branched-chain and aromatic amino acids and cardiometabolic risk in Black African and Asian Indian populations.

INTRODUCTION: Studies have shown that systemic levels of branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) are elevated in cardiometabolic diseases (CMDs) in populations resident in high income countries. However, little is known about the association of BCAAs and AAAs with metabolic syndrome and its components in Asian Indian (AI) and Black African (BA) populations. OBJECTIVE: The aim of this study was to describe the association of BCAAs and AAAs with the metabolic syndrome, its individual components and insulin resistance in AI and BA populations. METHODS: Serum samples collected from AI (n = 349) and BA (n = 369) subjects were used to measure levels of BCAAs and AAAs by ultra-pressure liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Anthropometric, demographic and cardiometabolic variables were measured in all subjects. RESULTS: The sum of BCAAs and AAAs was higher in AIs compared to BAs. The BCAAs and AAAs were positively associated with insulin resistance, metabolic syndrome and its individual components. This was particularly the case for AI subjects, in unadjusted regression models. However, these associations were non-significant after adjusting for co-variates, particularly visceral adipose tissue (VAT). Triglyceride levels were significantly associated with valine and leucine levels in BAs even after adjustment for co-variates. Lastly, we found that fasting circulatory BCAA and AAA levels are strongly correlated with VAT in both populations. CONCLUSION: This study identified specific associations of serum valine and leucine levels with triglycerides in BAs. The association of amino acids with CMDs was observed in AIs, but was found to be the result of confounding by VAT. Further studies are required to determine whether BCAAs and AAAs are aetiological factors in CMDs and how VAT modulates their serum levels.

Hepcidin and GDF-15 are potential biomarkers of iron deficiency anaemia in chronic kidney disease patients in South Africa.

BACKGROUND: Anaemia is a common presenting feature among patients with chronic kidney disease (CKD) and it is associated with poor clinical outcomes and quality of life. It is not clear if growth differentiation factor-15 (GDF-15) or hepcidin are useful as early markers of iron deficiency anaemia (IDA) among non-dialysis CKD patients. We therefore evaluated the diagnostic validity of GDF-15 and hepcidin as biomarkers of IDA among non-dialysis CKD patients in Johannesburg, South Africa. METHOD: An analytic cross-sectional study was conducted among non-dialysis CKD patients (n = 312) and apparently healthy controls (n = 184) from June to December 2016 at an Academic Hospital, in Johannesburg, South Africa. An interviewer administered proforma was used to obtain the socio-biological and clinical characteristics of the participants. Serum levels of GDF-15 and hepcidin were determined. Predictive logistic regression models were built and post estimation receiver operator characteristics were determined to evaluate diagnostic validity of hepcidin and GDF-15 for absolute and functional iron deficiency anaemia. RESULTS: About half (50.6%) of the participants were female while the participants' mean age was 49.7 ± 15.8 years. The predictive value of diagnosing absolute IDA among CKD patients using GDF-15 was 74.02% (95% CI: 67.62-80.42%) while the predictive value of diagnosing functional IDA among CKD patients using hepcidin was 70.1% (95% CI: 62.79-77.49%).There was a weak negative correlation between hepcidin levels and GFR (r = - 0.19, p = 0.04) in anaemic CKD patients, and between serum GDF-15 and haemoglobin (r = - 0.34, p = 0.001). Serum ferritin (ß = 0.00389, P-value< 0.001), was a predictor of log hepcidin. MCHC (ß = - 0.0220, P-value 0.005) and CKD stage (ß = 0.4761, P-value < 0.001), race (ß = 0.3429, P-value = 0.018) were predictors of log GDF-15. Both GDF-15 (adj OR: 1.0003, 95%CI: 1.0001-1.0005, P = 0.017) and hepcidin (adj OR: 1.003, 95%CI: 1.0004-1.0055, P = 0.023) were associated with iron deficiency anaemia after multiple linear regression modelling. CONCLUSION: Serum GDF-15 is a potential biomarker of absolute IDA, while hepcidin levels can predict functional IDA among CKD patients.

Diagnostic accuracy of plasma kynurenine/tryptophan ratio, measured by enzyme-linked immunosorbent assay, for pulmonary tuberculosis.

INTRODUCTION: The World Health Organization has identified the need for a non-sputum-based test capable of detecting active tuberculosis (TB) as a priority. The plasma kynurenine-to-tryptophan (K/T) ratio, largely mediated by activity of the enzyme indoleamine 2,3-dioxygenase, may have potential as a suitable biomarker for active TB. METHOD: We evaluated a commercial enzyme-linked immunosorbent assay (ELISA) in comparison to mass spectrometry for measuring the K/T ratio. We also used ELISA to determine the K/T ratio in plasma from patients with active TB compared to latently infected controls, with and without HIV. RESULTS: The two methods showed good agreement, with a mean bias of 0.01 (limit of agreement from -0.06 to 0.10). Using ELISA, it was found that HIV-infected patients with active TB disease had higher K/T ratios than those without TB (median, 0.101 [interquartile range (IQR), 0.091-0.140] versus 0.061 [IQR, 0.034-0.077], P<0.0001). At a cutoff of 0.080, the K/T ratio produced a sensitivity of 90%, a specificity of 80%, a positive predictive value (PPV) of 82%, and a negative predictive value (NPV) of 90%. In a receiver operating characteristics analysis, the K/T ratio had an area under the curve of 0.93. HIV-uninfected patients with active TB also had higher K/T ratios than those with latent TB infections (median, 0.064 [IQR, 0.040-0.088] versus 0.022 [IQR, 0.016-0.027], P<0.0001). A cutoff of 0.040 gave a sensitivity of 85%, a specificity of 92%, a PPV of 91%, and an NPV of 84%. CONCLUSION: The plasma K/T ratio is a sensitive biomarker for active TB. The K/T ratio can be measured from blood using ELISA. The K/T ratio should be evaluated as an initial test for TB.

Drug level testing as a strategy to determine eligibility for drug resistance testing after failure of ART: a retrospective analysis of South African adult patients on second-line ART.

INTRODUCTION: When protease inhibitor (PI)-based second-line ART fails, guidelines recommend drug resistance testing and individualized third-line treatment. However, PI-resistant viral strains are rare and drug resistance testing is costly. We investigated whether less costly PI-exposure testing can be used to select those patients who would benefit most from drug resistance testing. METHODS: We performed a retrospective analysis of South African adults living with HIV experiencing failure of ritonavir-boosted-lopinavir (LPV/r)-based second-line ART for whom drug resistance testing results were available. We included patients who received plasma-based drug resistance testing at a central South African reference laboratory in 2017 and patients who received dried blood spots (DBS)-based drug resistance testing at a rural South African clinic between 2009 and 2017. PI-exposure testing was performed on remnant plasma or DBS using liquid chromatography mass spectrometry (LCMS). Additionally, a low-cost immunoassay was used on plasma. Population genotypic drug resistance testing of the pol region was performed on plasma and DBS using standard clinical protocols. RESULTS: Samples from 544 patients (494 plasma samples and 50 DBS) were included. Median age was 41.0 years (IQR: 33.3 to 48.5) and 58.6% were women. Median HIV-RNA load was 4.9 log10 copies/mL (4.3 to 5.4). Prevalence of resistance to the NRTI-backbone was 70.6% (349/494) in plasma samples and 56.0% (28/50) in DBS. Major PI-resistance mutations conferring high-level resistance to LPV/r were observed in 26.7% (132/494) of plasma samples and 12% (6/50) of DBS. PI-exposure testing revealed undetectable LPV levels in 47.0% (232/494) of plasma samples and in 60.0% (30/50) of DBS. In pooled analysis of plasma and DBS samples, detectable LPV levels had a sensitivity of 90% (84% to 94%) and a negative predictive failure of 95% (91% to 97%) for the presence of major LPV/r resistance. CONCLUSIONS: PI-exposure testing revealed non-adherence in half of patients experiencing failure on second-line ART and accurately predicted the presence or absence of clinically relevant PI resistance. PI-exposure testing constitutes a novel screening strategy in patients with virological failure of ART that can differentiate between different underlying causes of therapy failure and may allow for more effective use of limited resources available for drug resistance testing.

Toward Respiratory Support of Critically Ill COVID-19 Patients Using Repurposed Kidney Hollow Fiber Membrane Dialysers to Oxygenate the Blood.

The COVID-19 pandemic has highlighted resource constraints in respiratory support. The oxygen transfer characteristics of a specific hollow fiber membrane dialyser was investigated with a view to repurposing the device as a low-cost, readily available blood oxygenator. Oxygen transfer in a low-flux hollow fiber dialyser with a polysulfone membrane was studied by passing first water and then blood through the dialyser in countercurrent to high-purity oxygen. Oxygen transfer rates of about 15% of the nominal 250 ml (STP)/min of a typical adult oxygen consumption rate were achieved for blood flow rates of 500 ml/min. Using two such dialysis devices in parallel could provide up to 30% of the nominal oxygen consumption. Specific hollow fiber dialysis devices operating with suitable pumps in a veno-venous access configuration could provide a cost-effective and readily available supplementation of respiratory support in the face of severe resource constraints.

Relationship of Visceral Fat and Adipokines with Cardiometabolic Diseases in Psoriasis.

As part of a larger cross-sectional, case-control study on cardiometabolic diseases in psoriasis this study investigated the association of visceral fat and serum adipokines with psoriasis and cardiometabolic diseases. A total of 103 patients with psoriasis and 98 controls, matched for body mass index, ethnicity and sex, were recruited over 15 months. Abdominal visceral fat was measured by computerized tomo-graphy. Logistic regression analysis revealed that visceral fat was associated with psoriasis (odds ratio (95% confidence interval): 1.56 (1.15, 2.11)), hyper-triglyceridaemia (1.67 (1.22, 2.28)), low high-density lipoprotein (1.63 (1.19, 2.22)) and type 2 diabetes (1.77 (1.24, 2.54)), (p < 0.005 for all). These respective associations were linked to serum interleukin-6, adiponectin, tumour necrosis factor and insulin resistance. Psoriasis was associated with type 2 diabetes (7.94 (2.64, 23.9)), independent of visceral fat. These data suggest that visceral fat and its mediators play a key role in psoriasis-associated cardiometabolic diseases. Psoriasis itself is associated with an increased risk of type 2 diabetes.

Maternal plasma vitamin D levels and associated determinants in late pregnancy in Harare, Zimbabwe: a cross-sectional study.

BACKGROUND: The importance of vitamin D in bone health and calcium homeostasis has been well documented. However, emerging evidence supports the role of vitamin D beyond its recognised traditional roles. In pregnancy, vitamin D levels are crucial in sustaining both the maternal stores and optimal growth of the foetus. In Southern Africa, there is paucity of data on vitamin D in pregnancy and related outcomes. To expand this body of knowledge, we assessed vitamin D levels in late pregnancy and (if any) associated maternal determinants in Harare, Zimbabwe. METHODS: Study participants comprised of 138 pregnant Zimbabwean women in their third trimester. These were stratified by HIV status; sampling median (IQR) gestation for HIV negative study participants was 34 weeks (26-41) and 31 weeks (20-40) in the HIV positive participants. Maternal plasma 25 hydroxyvitamin (OH) Dlevels were measured using the ClinPrepHigh Pressure Liquid Chromatography (HPLC) kit. Statistical analysis was carried out using the STATA statistical package version 13. A p-value of < 0.05was considered to be statistically significant. RESULTS: HIV infected participants had significantly higher mean 25 (OH) D concentration (112 ± 33.4 nmol/L) compared to the HIV uninfected (100 ± 27.1 nmol/L), p = 0.032.Participants whose samples were collected during summer had higher maternal 25 (OH) D levels than those cART duration and maternal 25 (OH) D levels (p = 0.031, Spearman correlation =0.28). CONCLUSIONS: Our findings show high mean levels of maternal 25 (OH) D in late pregnancy in our setting and in the absence of vitamin D supplementation. Both HIV infection and season are significant determinants of maternal vitamin D levels. Summer season is associated with higher maternal plasma 25 (OH) D levels. HIV infection is associated with increased maternal vitamin D levels. Prolonged use of cART, Tenolam E is associated with improved maternal 25(OH) D levels.

Non-nucleoside reverse transcriptase inhibitor levels among HIV-exposed uninfected infants at the time of HIV PCR testing - findings from a tertiary healthcare facility in Pretoria, South Africa.

INTRODUCTION: To date, very little programmatic data has been published regarding serial antiretroviral (ARV) levels in infants exposed to maternal treatment and/or infant prophylaxis during the first months of life. Such data provide the opportunity to describe the proportion of infants exposed to virologically suppressive levels of ARVs and to gauge adherence to the prevention of mother-to-child transmission of HIV (PMTCT) programme. METHODS: From August 2014 to January 2016, HIV-exposed infants born at Kalafong Provincial Tertiary Hospital in Pretoria, South Africa were enrolled as part of an observational cohort study. Plasma samples from HIV-exposed uninfected infants were obtained at birth, 6-weeks, 10-weeks and 14-weeks of age and quantitative efavirenz (EFV) and nevirapine (NVP) drug level testing performed using liquid chromatography-mass spectrometry, irrespective of maternal ARV regimen. Descriptive analysis of EFV and NVP levels in relation to self-reported maternal and infant ARV exposure was performed. EFV levels >500 ng/mL and NVP levels >100 ng/mL were reported based on studies suggesting that trough levels above these thresholds are associated with virological suppression and PMTCT respectively. RESULTS: Among 66 infants exposed to maternal EFVin utero, 29 (44%) had virologically suppressive plasma EFV levels at birth, with a median level of 1665 ng/mL (IQR: 1094 to 3673). Among infants who were exclusively breastfed at 6-, 10- and 14 weeks, 13/48 (27%), 5/25 (25%) and 0/21 (0%) had virologically suppressive EFV levels. Among 64 infants whose mothers reported administering daily infant NVP at time of their 6-week HIV PCR test, only 45 (70%) had NVP levels above the minimum prophylactic trough level. CONCLUSIONS: During the first 10-weeks after delivery, a quarter of breastfed infants born to women on an EFV-containing treatment regimen maintained virologically suppressive EFV plasma levels. This finding highlights the importance of both careful monitoring of ARV side effects and repeat HIV PCR after the first few months of life among HIV-exposed uninfected infants. As 30% of infants had inadequate NVP plasma levels at 6-weeks of age, adherence counselling to caregivers regarding infant prophylaxis needs to be enhanced to further reduce mother-to-child transmission of HIV.

High burden of the metabolic syndrome and its component disorders in South Africans with psoriasis.

BACKGROUND: Psoriasis is associated with cardiometabolic diseases (CMDs) in Caucasians, but no data is available from sub-Saharan populations on either CMD prevalence or psoriasis risk factors. Our aim was to investigate the prevalence of CMDs in a predominantly non-Caucasian cohort of South Africans with psoriasis and to determine the principal risk factors associated with psoriasis. METHODS: This was a cross-sectional case-control study of adult psoriasis patients (n = 103) and controls (n = 98), comparing sociodemographic, anthropometric, clinical, and biochemical characteristics. The groups were matched for gender, ethnicity, and body mass index (BMI). RESULTS: The prevalence of metabolic syndrome (MetS) (52.4% vs. 33.7%; P = 0.007), type 2 diabetes (T2D) (25.2% vs. 4.1%; P < 0.0001), and hypertension (70.9% vs. 46.6%; P = 0.001) were all higher in the psoriasis group. High-sensitivity CRP was higher in psoriasis patients than controls (4.70 (2.00, 10.9) vs. 2.00 (1.10, 4.80) ng/ml; P < 0.0005). Multivariable logistic regression analysis showed that severe psoriasis was independently associated with MetS (odds ratio [95% CIs]: 4.42 [1.72, 11.4]; P = 0.002), T2D (11.3 [3.07, 41.3]; P = 0.0002), and hypertension (2.48 [0.97, 6.32]; P = 0.05), whilst for psoriasis the principal risk factors were smoking (3.87 [1.97, 7.63]; P < 0.0001) and hsCRP (1.05 [1.00, 1.10]; P = 0.029), with completion of high school (0.23 [0.11, 0.48]; P < 0.0001) being protective. CONCLUSIONS: In this population, psoriasis is characterized by a high burden of CMDs, particularly in those subjects with severe psoriasis. Inflammation plays a role in the etiology of psoriasis, whilst smoking and poor education further increase disease risk.

Plasma Indoleamine 2, 3-Dioxygenase, a Biomarker for Tuberculosis in Human Immunodeficiency Virus-Infected Patients.

BACKGROUND: There is no biomarker for diagnosing active tuberculosis in patients with human immunodeficiency virus (HIV) infection. Indoleamine 2, 3-dioxygenase (IDO) is an immunoregulatory enzyme that breaks down tryptophan (Trp) to metabolites known as kynurenines (Kyns). We investigated whether IDO activity, as measured by the ratio of Kyn to Trp, could be used to diagnose or predict active tuberculosis disease in HIV-infected adults. METHODS: Kyn and Trp concentrations were measured using ultraperformance liquid chromatography mass spectrometry in plasma samples from 32 HIV-infected patients in whom active tuberculosis developed and who were followed up prospectively. We compared to 70 HIV-infected control subjects from the same cohort in whom tuberculosis did not develop, matched by age, sex, and CD4 cell count, and 37 unmatched HIV-infected patients with a diagnosis of pneumonia. Clinical parameters, including body mass index, CD4 cell count, HIV load, and C-reactive protein levels were analyzed. RESULTS: At the time of tuberculosis diagnosis, IDO activity was significantly higher in patients with tuberculosis than in controls (P < .001). Six months before tuberculosis diagnosis, IDO activity was significantly higher in all patients who later developed tuberculosis (P < .001) than controls. After 6 months of tuberculosis treatment, IDO activity in patients with tuberculosis declined to levels similar to those in controls. IDO activity was 4-fold higher in patients with tuberculosis than in those with pneumonia, and could be used to distinguish them. With a receiver operating characteristic curve, IDO activity had a sensitivity of 97%, a specificity of 99%, and positive and negative predictive values of 89% and 100% for detecting active tuberculosis disease. CONCLUSION: Plasma IDO activity is suitable as a biomarker of active tuberculosis in HIV-positive patients.

Ex Vivo and In Vivo Characterization of Interpolymeric Blend/Nanoenabled Gastroretentive Levodopa Delivery Systems.

One approach for delivery of narrow absorption window drugs is to formulate gastroretentive drug delivery systems. This study was undertaken to provide insight into in vivo performances of two gastroretentive systems (PXLNET and IPB matrices) in comparison to Madopar® HBS capsules. The pig model was used to assess gastric residence time and pharmacokinetic parameters using blood, cerebrospinal fluid (CSF), and urine samples. Histopathology and cytotoxicity testing were also undertaken. The pharmacokinetic parameters indicated that levodopa was liberated from the drug delivery systems, absorbed, widely distributed, metabolized, and excreted. Cmax were 372.37, 257.02, and 461.28 ng/mL and MRT were 15.36, 14.98, and 13.30 for Madopar HBS capsules, PXLNET, and IPB, respectively. In addition, X-ray imaging indicated that the gastroretentive systems have the potential to reside in the stomach for 7 hours. There was strong in vitro-in vivo correlation for all formulations with r2 values of 0.906, 0.935, and 0.945 for Madopar HBS capsules, PXLNET, and IPB, respectively. Consequently, PXLNET and IPB matrices have pertinent potential as gastroretentive systems for narrow absorption window drugs (e.g., L-dopa) and, in this application specifically, enhanced the central nervous system and/or systemic bioavailability of such drugs.

Body composition in the Study of Women Entering and in Endocrine Transition (SWEET): A perspective of African women who have a high prevalence of obesity and HIV infection.

OBJECTIVES: Little data are available for sub-Saharan African women on changes in body composition in menopause transition (MT). The study aimed to determine whether there are differences in body adiposity, lean muscle mass, and bone mineral density (BMD) across MT groups in urban African women, who have a high prevalence of obesity and HIV infection, and if this is related to an altered hormonal milieu. DESIGN: Participants were 702 black urban women. Menopause stage was defined using STRAW+10 criteria. Levels of follicle stimulating hormone (FSH), estradiol (E2), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), testosterone (T) and sex hormone blinding globulin (SHBG) were measured. Body composition was measured with dual-energy X-ray absorptiometry (DXA) and ultrasound scans. RESULTS: Whole body lean mass (p=0.002) and BMD (p<0.0005) were significantly lower in postmenopausal compared to premenopausal groups. Estradiol (p<0.0005), SHBG (p<0.0005) and DHEAS (p=0007) were significantly lower in post- than premenopausal groups, while FSH was higher (p<0.0005). FSH correlated negatively (ß=-2.06, p<0.0005) with total lean mass while E2 correlated positively (ß=20.0, p=0.002) with BMD. Use of antiretroviral therapy (ART) correlated negatively with total fat mass (ß=-2.92, p=0.008) and total bone mineral content (BMC; ß=-78.8, p=0.003). CONCLUSIONS: The MT in this population is characterized by lower whole body lean mass and BMD in post- compared to premenopausal subjects but there are minimal differences in fat mass. Lower lean mass and BMD were associated with higher FSH and lower E2 serum levels, respectively. Use of ART was associated with lower fat mass and BMC.

Staging reproductive aging using Stages of Reproductive Aging Workshop + 10 in black urban African women in the Study of Women Entering and in Endocrine Transition.

OBJECTIVE: There has been limited research on accurate staging of the menopausal transition in sub-Saharan African women. Our aim was to assess the usefulness of the Stages of Reproductive Aging Workshop + 10 (STRAW + 10) criteria in staging ovarian aging in black South African women, examining whether obesity has any effect on the menopausal transition. METHODS: The study enrolled 702 women aged 40 to 60 years. STRAW + 10 criteria were used to categorize the stages of reproductive aging. The Menopause Rating Scale was used to measure the prevalence of vasomotor symptoms. Follicle-stimulating hormone (FSH) and estradiol levels were used as supportive criteria for staging. Human immunodeficiency virus status was assessed using a point-of-care method. RESULTS: Reported age at final menstrual period (FMP) was higher in women interviewed within 4 years of FMP (mean [SD], 49.0 [3.80] y) than in women interviewed 10 years or more after FMP (mean [SD], 42.0 [4.06] y; P < 0.0005). In women within 4 years of FMP, lower body mass index was associated with earlier age at FMP. FSH levels increased and estradiol levels decreased (P < 0.0005 for both trends) across seven staging groups. Human immunodeficiency virus status had no effect on menopause symptoms. Obesity (body mass index ≥35.0 kg/m) was associated with severe vasomotor symptoms. CONCLUSIONS: Reporting of age at FMP is unreliable in women interviewed 4 years or more after the event. STRAW + 10 seems accurate in staging reproductive aging, as confirmed by the strong association of FSH and estradiol levels with the menopausal transition stage. STRAW + 10 may be appropriate for use in resource-limited settings in the absence of biomarkers. Biocultural methods may be useful in assessing the menopausal transition in culturally diverse women.