FGFR2 genetic variants in women with breast cancer.

Black African populations are more genetically diverse than others, but genetic variants have been studied primarily in European populations. The present study examined the association of four single nucleotide polymorphisms (SNPs) of the fibroblast growth factor receptor 2, associated with breast cancer in non­African populations, with breast cancer in Black, southern African women. Genomic DNA was extracted from whole blood samples of 1,001 patients with breast cancer and 1,006 controls (without breast cancer), and the rs2981582, rs35054928, rs2981578, and rs11200014 polymorphisms were analyzed using allele­specific Kompetitive allele­specific PCR™, and the χ2 or Fisher's exact tests were used to compare the genotype frequencies. There was no association between those SNPs and breast cancer in the studied cohort, although an association was identified between the C/C homozygote genotype for rs2981578 and invasive lobular carcinoma. These results show that genetic biomarkers of breast cancer risk in European populations are not necessarily associated with risk in sub­Saharan African populations. African populations are more heterogenous than other populations, and the information from this population can help focus genetic risks of cancer in this understudied population.

Altered microRNA expression in patients with sarcoidosis.

Background Sarcoidosis is a granulomatous multisystem disease of uncertain aetiology. The disease has major inflammatory and immune components; however, the immunopathogenesis is not well understood. Micro ribonucleic acids (microRNAs) are classes of miniature, single-stranded, non-coding RNAs. Their key recognised role includes mediating the silencing of target genes post-transcriptionally. Recently, the role of miRNAs has gained interest in numerous disorders, suggested as being involved in pathogenesis of those diseases and acting as disease markers. Very little is known about the role of miRNAs in sarcoidosis, with nothing known regarding miRNAs in South African patients. The main objective, therefore, was to investigate the serum expression of approximately 800 miRNAs in patients with sarcoidosis compared with race-, age- and gender-matched healthy controls. Methods A total of six patients and six matched controls participated in this study. Whole blood samples were collected in EDTA tubes, processed and the plasma retained. RNA was extracted from the stored plasma samples using the QIAGEN miRNeasy Mini Kit® and concentrated using a salt-ethanol precipitation. The extracted miRNA was profiled using an nCounter® miRNA human v3 expression assay and data analysed using the nSolver™ Analysis Software. Results After excluding one sample/control pair because of cellular RNA contamination, the remaining five patient and five matched control samples were analysed, and 145 miRNAs were found to be potentially differentially expressed. On applying a Bonferroni correction, the only miRNA that was significantly different was miRNA let-7a-5p, which was significantly overexpressed (141-fold change; p<0.0003) in patients compared with controls. Conclusion This is the first miRNA report of differentially expressed miRNAs in the serum of patients with sarcoidosis and matched healthy controls in South Africa. The results obtained suggest that miRNAs may play a role in sarcoidosis pathogenesis. Whether these molecules have diagnostic or prognostic implications, needs future studies recruiting larger patient cohorts.

PAM50 intrinsic subtypes, risk of recurrence score and breast cancer survival in HIV-positive and HIV-negative patients-a South African cohort study.

PURPOSE: Treatment decision making for patients with breast cancer increasingly depends on analysis of markers or systems for estimating risk of breast cancer recurrence. Breast cancer intrinsic subtypes and risk of recurrence (ROR) scores have been found to be valuable in predicting survival and determining optimal treatment for individual patients. We studied the association of breast cancer survival with the PAM50 gene expression assay in HIV-positive and HIV-negative patients. METHOD: RNA was extracted from formalin-fixed paraffin-embedded specimens of histologically confirmed invasive carcinoma and was purified using the AllPrep® DNA/RNA FFPE kit, Qiagen (Hilden, Germany). The NanoString RUO PAM50 algorithm was used to determine the molecular subtype and the risk of recurrence score of each sample. The overall and disease-free survival were determined with comparison made among HIV-positive and -negative patients. We then generated Kaplan-Meier survival curves, calculated p-values and estimated hazard ratios and their 95% confidence intervals using Cox regression models. RESULTS: Of the 384 RNA samples analysed, 98.4% met the required RNA quality standard and the specified QC threshold for the test. Luminal B was the most common PAM50 intrinsic subtype and 82.1% of patients were at high risk for disease recurrence based on ROR score. HIV infection, PAM50-based HER2-enriched and basal-like intrinsic subtypes, and high ROR were associated with poor overall and disease-free survival. HIV-positive patients with luminal A & B subtypes had significantly worse survival outcomes than HIV-negative luminal patents. CONCLUSION: Aggressive tumour biology was common in our cohort. HIV infection, PAM50 HER2-enriched,basal-like intrinsic subtypes and high ROR score were associated with poor overall and disease-free survival. HIV infection impacted survival in patients with luminal subtypes only.

Discordance between PAM50 intrinsic subtyping and immunohistochemistry in South African women with breast cancer.

PURPOSE: Breast cancer is a heterogeneous disease with different gene expression profiles, treatment options and outcomes. In South Africa, tumors are classified using immunohistochemistry. In high-income countries multiparameter genomic assays are being utilized with implications for tumor classification and treatment. METHODS: In a cohort of 378 breast cancer patients from the SABCHO study, we investigated the concordance between tumor samples classified by IHC and the PAM50 gene assay. RESULTS: IHC classified patients as ER-positive (77.5%), PR-positive (70.6%), and HER2-positive (32.3%). These results, together with Ki67, were used as surrogates for intrinsic subtyping, and showed 6.9% IHC-A-clinical, 72.7% IHC-B-clinical, 5.3% IHC-HER2-clinical and 15.1% triple negative cancer (TNC). Typing using the PAM50 gave 19.3% luminal-A, 32.5% luminal-B, 23.5% HER2-enriched and 24.6% basal-like. The basal-like and TNC had the highest concordance, while the luminal-A and IHC-A group had the lowest concordance. By altering the cutoff for Ki67, and realigning the HER2/ER/PR-positive patients to IHC-HER2, we improved concordance with the intrinsic subtypes. CONCLUSION: We suggest that the Ki67 be changed to a cutoff of 20-25% in our population to better reflect the luminal subtype classifications. This change would inform treatment options for breast cancer patients in settings where genomic assays are unaffordable.

High risk APOL1 genotypes and kidney disease among treatment naïve HIV patients at Kano, Nigeria.

INTRODUCTION: Racial disparities are known in the occurrence of kidney disease with excess risks found among people of African descent. Apolipoprotein L1 (APOL1) gene variants G1 and G2 are associated with kidney disease among HIV infected individuals of African descent in the USA as well as among black population in South Africa. We set out to investigate the prevalence of these high-risk variants and their effects on kidney disease among HIV infected patients in Northern Nigeria with hitherto limited information despite earlier reports of high population frequencies of these alleles from the Southern part of the country. METHODS: DNA samples obtained from the whole blood of 142 participants were genotyped for APOL1 G1 and G2 variants after initial baseline investigations including assessment of kidney function. Participants comprised 50 HIV positive patients with no evidence of kidney disease, 52 HIV negative individuals with no kidney disease and 40 HIV positive patients with chronic kidney disease (CKD) evidenced by persistent proteinuria and/or reduced eGFR, who also had a kidney biopsy. All the HIV positive patients were newly diagnosed and treatment naïve. RESULTS: The distribution of the APOL1 genotypes among the study participants revealed that 24.6% had a G1 risk allele and 19.0% a G2. The frequency of the High Risk Genotype (HRG) was 12.5% among those with CKD compared to 5.8% in the HIV negative group and zero in the HIV positive no CKD group. Having the HRG was associated with a higher odds for developing HIV Associated Nephropathy (HIVAN) (2 vs 0 risk alleles: OR 10.83, 95% CI 1.38-84.52; P = 0.023; 2 vs 0 or 1 risk alleles: OR 5.5, 95% CI 0.83-36.29; P = 0.07). The HRG was also associated with higher odds for Focal Segmental Glomerulosclerosis (FSGS) (2 vs 0 risk alleles: OR 13.0, 95% CI 2.06-81.91; P = 0.006 and 2 vs 0 or 1 risk alleles: OR 9.0, 95%CI 1.62-50.12; P = 0.01) when compared to the control group. CONCLUSION: This study showed a high population frequency of the individual risk alleles of the APOL1 gene with higher frequencies noted among HIV positive patients with kidney disease. There is high association with the presence of kidney disease and especially FSGS and HIVAN among treatment naive HIV patients carrying two copies of the HRG.

Demographic and clinical profile of black patients with chronic kidney disease attending a tertiary hospital in Johannesburg, South Africa.

BACKGROUND: The prevalence of chronic kidney disease (CKD) is increasing worldwide; black patients have an increased risk of developing CKD and end stage kidney disease (ESKD) at significantly higher rates than other races. METHODS: A cross sectional study was carried out on black patients with CKD attending the kidney outpatient clinic at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH) in South Africa, between September 2019 to March 2020. Demographic and clinical data were extracted from the ongoing kidney outpatient clinic records and interviews, and were filled in a questionnaire. Patients provided blood and urine for laboratory investigations as standard of care, and data were descriptively and inferentially entered into REDcap and analysed using STATA version 17. Multivariable logistic regression analysis was used to identify demographic and clinical variables associated with advanced CKD. RESULTS: A total of 312 black patients with CKD were enrolled in the study with a median age of 58 (IQR 46-67) years; 58% patients had advanced CKD, 31.5% of whom had grossly increased proteinuria, 96.7% had hypertension, 38.7% had diabetes mellitus and 38.1% had both hypertension and diabetes mellitus. In patients with advanced CKD, the median age was 61 (IQR 51-69) years, eGFR 33 (30-39) mL/min/1.73 m2, serum bicarbonate 22 (IQR 20-24), haemoglobin 12.9 (IQR 11.5-14.0) g/dl and serum uric acid 0.43 (IQR 0.37-0.53). The prevalence of metabolic acidosis was 62.4%, anemia 46.4% and gout 30.9% among those with advanced CKD, while the prevalence of metabolic acidosis and anaemia was 46.6% and 25.9% respectively in those with early CKD. Variables with higher odds for advanced CKD after multivariable logistic regression analysis were hypertension (OR 3.3, 95% CI 1.2-9.2, P = 0.020), diabetes mellitus (OR 1.8, 95% CI 1.1-3.3, P = 0.024), severe proteinuria (OR 3.5, 95% CI 1.9-6.5, P = 0.001), angina (OR 2.5, 95% CI 1.2-5.1, P = 0.008), anaemia (OR 2.9, 95% CI 1.7-4.9, P = 0.001), hyperuricemia (OR 2.4, 95% CI 1.4-4.1, P = 0.001), and metabolic acidosis (OR 2.0, 95% CI 1.2-3.1, P = 0.005). Other associations with advanced CKD were loss of spouse (widow/widower) (OR 3.2, 95% CI 1.4-7.4, P = 0.006), low transferrin (OR 2.4, 95% CI 1.1-5.1, P = 0.028), hyperkalemia (OR 5.4, 95% CI 1.2-24.1, P = 0.029), use of allopurinol (OR 2.4, 95% CI 1.4-4.3, P = 0.005) and doxazosin (OR 1.9, 95% CI 1.2-3.1, P = 0.006). CONCLUSION: Hypertension and diabetes mellitus were strongly associated with advanced CKD, suggesting a need for primary and secondary population-based prevention measures. Metabolic acidosis, anemia with low transferrin levels, hyperuricemia and hyperkalemia were highly prevalent in our patients, including those with early CKD, and they were strongly associated with advanced CKD, requiring clinicians and dietitians to be proactive in supporting the needs of CKD patients in meeting their daily dietary requirements towards preventing and slowing the progression of CKD.

The association of age at menarche and adult height with mammographic density in the International Consortium of Mammographic Density.

BACKGROUND: Early age at menarche and tall stature are associated with increased breast cancer risk. We examined whether these associations were also positively associated with mammographic density, a strong marker of breast cancer risk. METHODS: Participants were 10,681 breast-cancer-free women from 22 countries in the International Consortium of Mammographic Density, each with centrally assessed mammographic density and a common set of epidemiologic data. Study periods for the 27 studies ranged from 1987 to 2014. Multi-level linear regression models estimated changes in square-root per cent density (√PD) and dense area (√DA) associated with age at menarche and adult height in pooled analyses and population-specific meta-analyses. Models were adjusted for age at mammogram, body mass index, menopausal status, hormone therapy use, mammography view and type, mammographic density assessor, parity and height/age at menarche. RESULTS: In pooled analyses, later age at menarche was associated with higher per cent density (ß√PD = 0.023 SE = 0.008, P = 0.003) and larger dense area (ß√DA = 0.032 SE = 0.010, P = 0.002). Taller women had larger dense area (ß√DA = 0.069 SE = 0.028, P = 0.012) and higher per cent density (ß√PD = 0.044, SE = 0.023, P = 0.054), although the observed effect on per cent density depended upon the adjustment used for body size. Similar overall effect estimates were observed in meta-analyses across population groups. CONCLUSIONS: In one of the largest international studies to date, later age at menarche was positively associated with mammographic density. This is in contrast to its association with breast cancer risk, providing little evidence of mediation. Increased height was also positively associated with mammographic density, particularly dense area. These results suggest a complex relationship between growth and development, mammographic density and breast cancer risk. Future studies should evaluate the potential mediation of the breast cancer effects of taller stature through absolute breast density.

Profiling Biomarkers in HIV Glomerular Disease - Potential for the Non-Invasive Diagnosis of HIVAN?

BACKGROUND: There is a wide spectrum of kidney pathology in human immunodeficiency virus (HIV) infection, affecting all structures of the kidney. The histology of HIV chronic kidney disease (CKD) is diverse, ranging from HIV-associated nephropathy (HIVAN) to focal glomerulosclerosis (FSGS), HIV-immune complex disease (HIV-ICD), other glomerulopathies and tubulo-interstitial nephritis. Definitive diagnosis is by kidney biopsy, an invasive procedure. However, serum and urinary biomarkers may be useful in predicting the histological diagnosis of HIVAN. PURPOSE: We wished to determine the utility of serum and urinary biomarkers in predicting the histological diagnosis of HIVAN. PATIENTS AND METHODS: We measured neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, transforming growth factor (TGF)-ß isoforms and bone morphogenetic protein (BMP)-7 in the serum and urine in patients with different histological forms of HIV glomerular disease. RESULTS: In HIVAN, we demonstrated increased levels of serum cystatin C and increased levels of serum and urinary NGAL. Urinary TGF-ß1 and TGF-ß2 levels were elevated in HIV-positive patients with CKD but were not significantly different in the different HIV histologies, while urinary BMP-7 levels were elevated in minimal change disease. CONCLUSION: This study confirmed the presence of increased serum and urinary biomarkers of tubular injury in patients with HIVAN, and increased urinary biomarkers of fibrosis in HIV CKD, and may indicate their value as a non-invasive diagnostic tool for the diagnosis of HIVAN.

Survival of south african women with breast cancer receiving anti-retroviral therapy for HIV.

PURPOSE: Breast cancer outcomes in sub-Saharan Africa is reported to be poor, with an estimated five-year survival of 50% when compared to almost 90% in high-income countries. Although several studies have looked at the effect of HIV in breast cancer survival, the effect of ARTs has not been well elucidated. METHODS: All females newly diagnosed with invasive breast cancer from May 2015-September 2017 at Charlotte Maxeke Johannesburg Academic and Chris Hani Baragwanath Academic Hospital were enrolled. We analysed overall survival and disease-free survival, comparing HIV positive and negative patients. Kaplan-Meier survival curves were generated with p-values calculated using a log-rank test of equality while hazard ratios and their 95% confidence intervals (CIs) were estimated using Cox regression models. RESULTS: Of 1019 patients enrolled, 22% were HIV positive. The overall survival (95% CI) was 53.5% (50.1-56.7%) with a disease-free survival of 55.8% (52.1-59.3) after 4 years of follow up. HIV infection was associated with worse overall survival (HR (95% CI): 1.50 (1.22-1.85), p < 0.001) and disease-free survival (OR (95% CI):2.63 (1.71-4.03), p < 0.001), especially among those not on ART at the time of breast cancer diagnosis. Advanced stage of the disease and hormone-receptor negative breast cancer subtypes were also associated with poor survival. CONCLUSION: HIV infection was associated with worse overall and disease-free survival. HIV patients on ARTs had favourable overall and disease-free survival and with ARTs now being made accessible to all the outcome of women with HIV and breast cancer is expected to improve.

Ki67 Immunohistochemistry Quantification in Breast Carcinoma: A Comparison of Visual Estimation, Counting, and ImmunoRatio.

BACKGROUND: Molecular analysis has shown that breast carcinomas can be classified into several intrinsic subtypes, with implications for management and prognosis. In the majority of pathology laboratories molecular analysis of each case is not possible and immunohistochemistry is used for subtyping. This includes analysis of hormone receptors as well as HER2-neu and Ki67. The methodology for the interpretation of the proliferation index using Ki67 remains an area of uncertainty. We investigated the degree of agreement between different methods of Ki67 interpretation. MATERIALS AND METHODS: We analyzed 204 breast core biopsies diagnostic of breast carcinoma using visual estimation/eyeballing (EB), ImmunoRatio, and counting by 2 pathologists (CP1 and CP2). The correlation between the different methods and the interobserver agreement between the 2 pathologists was assessed. Specific analysis was also done with respect to classification of cases into low Ki67 groups (using Ki67 values<14% and <20%) since this is critical in classifying tumors into luminal A and luminal B subtypes. RESULTS: Correlation between the different methods was best achieved comparing ImmunoRatio and CP1, and worst comparing CP1 and EB. Correlation was better when considering interobserver variability (CP1 vs. CP2). Comparing the number of cases classified as low Ki67 (<14% and <20%) the Cohen κ statistic varied from κ=0.267 to 0.814 with different methods. When limiting the analysis to cases with a Ki67 of 10% to 25% according to any method, there was greater disagreement. CONCLUSIONS: At the higher and lower Ki67 levels, the correlation between the methods of assessment was acceptable, however, at levels close to the cut-off values for lumial A versus luminal B, several patients would be differently classified by the different methods and therefore potentially receive suboptimal management.

Design and methods of the prevalence and pharmacogenomics of tenofovir nephrotoxicity in HIV-positive adults in south-western Nigeria study.

BACKGROUND: Individuals of African descent are at higher risk of developing kidney disease than their European counterparts, and HIV infection is associated with increased risk of nephropathy. Despite a safe renal profile in the clinical trials, long-term use of tenofovir disoproxil fumarate (TDF) has been associated with proximal renal tubulopathy although the underlying mechanisms remain undetermined. We aim to establish the prevalence of and risk factors for TDF-induced kidney tubular dysfunction (KTD) among HIV-I and II individuals treated with TDF in south-west Nigeria. Association between TDF-induced KTD and genetic polymorphisms in renal drug transporter genes and the APOL1 (Apolipoprotein L1) gene will be examined. METHODS: This study has two phases. An initial cross-sectional study will screen 3000 individuals attending the HIV clinics in south-west Nigeria for KTD to determine the prevalence and risk factors. This will be followed by a case-control study of 400 KTD cases and 400 matched controls to evaluate single nucleotide polymorphism (SNP) associations. Data on socio-demographics, risk factors for kidney dysfunction and HIV history will be collected by questionnaire. Blood and urine samples for measurements of severity of HIV disease (CD4 count, viral load) and renal function (creatinine, eGFR, phosphate, uric acid, glucose) will also be collected. Utility of urinary retinol binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (NAG) levels as surrogate markers of KTD will be evaluated. Genomic DNA will be extracted from whole blood and SNP analyses performed using the rhAMP SNP genotyping assays. Statistical analysis including univariate and multivariate logistic regression analyses will be performed to identify factors associated with KTD. DISCUSSION: In spite of TDF being the most commonly used antiretroviral agent and a key component of many HIV treatment regimens, it has potential detrimental effects on the kidneys. This study will establish the burden and risk factors for TDF-induced KTD in Nigerians, and explore associations between KTD and polymorphisms in renal transporter genes as well as APOL1 risk variants. This study may potentially engender an approach for prevention as well as stemming the burden of CKD in sub-Saharan Africa where GDP per capita is low and budgetary allocation for health is inadequate.

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.

Association of chronic inflammation and accelerated atherosclerosis among an indigenous black population with chronic kidney disease.

INTRODUCTION: Inflammation plays a major role in the development of atherosclerosis and cardiovascular morbidity and mortality in chronic kidney disease (CKD) patients. Toll-like receptor-4 (TLR4) is a major receptor for lipopolysaccharides (endotoxin) and other ligands involved in the pathogenesis of inflammation. We determined whether endotoxin levels and the presence of TLR4 polymorphisms are associated with markers of inflammation and atherosclerosis among South African CKD patients. MATERIALS AND METHODS: Endotoxin, lipopolysaccharide binding protein (LBP), serum CD14 (sCD14), interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and carotid intima media thickness (CIMT) were measured in 160 participants (120 CKD patients and 40 controls). Associations between endotoxins and CIMT in the presence of sCD14, IL-8 and MCP-1, were assessed using odds ratios. Participants were screened for the presence of Asp299Gly and Thr399Ile TLR4 polymorphisms, and CIMT and inflammatory markers were compared between subjects with and without TLR4 polymorphisms. RESULTS: Endotoxin levels correlated with sCD14 (r = 0.441, p<0.001) and MCP-1 (r = 0.388, p<0.001) levels while increased CIMT was associated with MCP-1 (r = 0.448, p<0.001), sCD14 levels (r = 0.476, p<0.001), LBP (r = 0.340, p<0.001), and IL-8 (r = 0.395, p<0.001). Atherosclerosis was associated with endotoxin levels (odds ratio: 4.95; 95% confidence interval: 2.52-9.73; p<0.001), and was predicted by higher serum levels of inflammatory markers. Analysis of patients with TLR4 polymorphisms showed reduced serum levels of inflammatory markers and CIMT values compared with the patients carrying the wild type TLR4 alleles. CONCLUSION: The study demonstrated associations between circulating endotoxaemia, systemic inflammation and accelerated atherosclerosis among South African CKD patients, and showed that the atherogenic predictive power of endotoxaemia was significantly increased by the presence of elevated levels of inflammatory markers. Additional findings, which must be confirmed, suggest that TLR4 polymorphisms are associated with low levels of inflammatory markers and CIMT values.

Parent-based prevention after parental weight loss surgery: a pilot case-series trial.

BACKGROUND: Overeating and obesity are elevated in children of parents who have undergone weight loss surgery. Parents who have undergone weight loss surgery often report their personal history of obesity interferes with their knowledge, skills, and self-efficacy in developing their children's healthy habits, thus reducing the likelihood of addressing obesogenic environmental factors. OBJECTIVES: This study examines whether a 6-session parent-based prevention after bariatric surgery online intervention is feasible and acceptable for parents. The study also explores the program's signal of efficacy in improving short-term outcomes related to decreased long-term risks for obesity by examining short-term impact on targeted parental cognitions, feeding practices, and child eating behaviors and physical activity habits. SETTING: University Hospital, United States. METHODS: Parents were recruited using flyers, clinician referrals, and social media. Measures assessed parental feeding practices, children's eating behaviors, daily hours of screen time, and outdoor play. RESULTS: Ten families enrolled and 7 completed the study. Parents found the intervention relevant and suitable for addressing their parenting concerns. Parental feeding behaviors, such as restriction and pressure to eat, reduced while tracking of sweets and high-fat snacks increased. Children reduced both emotional overeating and undereating. Children's daily hours of screen time reduced as well as their outdoor play time. CONCLUSIONS: Parent-based prevention after bariatric surgery aimed at helping parents who have undergone weight loss surgery engineer healthier family lifestyles is feasible, acceptable, and associated with reduced obesogenic risk factors.

APOL1 Genetic Variants Are Associated with Serum-Oxidized Low-Density Lipoprotein Levels and Subclinical Atherosclerosis in South African CKD Patients.

INTRODUCTION: Apolipoprotein L1 (APOL1) plays an important role in cholesterol metabolism and attenuation of low-density lipoprotein (LDL) oxidation. While protecting against Trypanosoma brucei rhodesiense infection, APOL1 risk alleles confer greater risk for CKD and cardiovascular disease among patients of African descent. OBJECTIVES: We investigated whether APOL1 risk variants are associated with atherosclerosis and oxidized LDL (OxLDL) levels among black South African CKD patients. METHODS: A cross-sectional study of 120 adult CKD patients and 40 controls was undertaken. DNA samples of participants were genotyped for APOL1 G1 and G2 variants. High-sensitivity C-reactive protein, serum lipids, and OxLDL levels were measured, and carotid doppler ultrasonography was performed on all participants. RESULTS: APOL1 alleles rs73885319, rs60910145, and rs71785313 had minor allele frequencies of 9.2, 8.8, and 17.5%, respectively, in the patients, and 8.8, 8.8, and 13.8%, respectively, in the controls. Of the 9 patients with 2 APOL1 risk alleles, 77.8% were compound G1/G2 heterozygotes and 22.2% were G2 homozygotes. Carriers of at least 1 APOL1 risk allele had a 3-fold increased risk of subclinical atherosclerosis (odds ratio 3.19; 95% confidence interval: 1.64-6.19; p = 0.01) compared to individuals with no risk alleles. Patients with 1 or 2 APOL1 risk alleles showed a significant increase in OxLDL levels when compared with those without the APOL1 risk allele. CONCLUSION: These findings suggest an increased risk for atherosclerosis in carriers of a single APOL1 risk variant, and the presence of APOL1 risk variants was associated with increased serum OxLDL levels in black South African CKD patients.

Biomarkers for Diagnosis and Prediction of Outcomes in Contrast-Induced Nephropathy.

BACKGROUND: Serum creatinine is suboptimal as a biomarker in the early diagnosis of contrast-induced nephropathy (CIN). In this study, we investigated a panel of novel biomarkers in the early diagnosis of CIN and in assessing patient outcomes. METHODS: This single-centre, nested, prospective case-controlled study included 30 patients with CIN and 60 matched controls. Serum and urine samples were collected before contrast administration and at 24 hours, 48 hours, and ≥5 days after contrast administration. Concentrations of NGAL, cystatin C, ß 2M, IL18, IL10, KIM1, and TNFα were determined using Luminex and ELISA assays. Outcomes were biomarker diagnostic discrimination performance for CIN and mortality after generation of area under receiver operating characteristic curves (AUROCs). RESULTS: Median serum levels for 24 h cystatin C (p < 0.01) and 48 h ß 2M levels (p < 0.001) and baseline urine NGAL (p=0.02) were higher in CIN patients compared to controls with AUROCs of 0.75, 0.78, and 0.74, respectively, for the early diagnosis of CIN. Serum ß 2M levels were higher in CIN patients at all time points. Elevated baseline serum concentrations of IL18 (p < 0.001), ß 2M (p=0.04), TNFα (p < 0.001), and baseline urine KIM (p=0.01) and 24 h urine NGAL (p=0.02) were significantly associated with mortality. Baseline serum concentrations of IL18, ß 2M, and TNFα showed the best discrimination performance for mortality with AUROCs, all >0.80. Baseline NGAL was superior for excluding patients at risk for CIN, with positive and negative predictive ranges of 0.50-0.55 and 0.81-0.88, respectively. Cystatin C (p=0.003) and ß 2M (p=0.03) at 24 h independently predicted CIN risk. ß 2M predicted increased mortality of 40% at baseline and 50% at 24 hours. CONCLUSION: Serum cystatin C at 24 h was the best biomarker for CIN diagnosis, while baseline levels of serum IL18, ß 2M, and TNFα were best for predicting prognosis.

The offspring of parents undergoing a weight loss surgery: a systematic review.

The offspring of parents with obesity are at an increased risk of developing this condition themselves because of genetic and environmental factors. One subgroup that may be at particularly high risk of developing obesity is the offspring of parents who have undergone weight loss surgery (PWLS). To date, little research has focused on these offspring or their parents. This systematic review addresses this gap by integrating available literature and assessing the quality of the evidence. To be included, studies were required to have researched characteristics of the offspring of PWLS or parental feeding practices within this population. After review, 12 studies met inclusion criteria. Findings include evidence for heightened risk of obesity among children of PWLS. However, research suggests these children may experience positive, although time-limited, health outcomes after their parents' surgeries. Quality of the evidence was rated as low, primarily because of the lack of randomized controlled studies and information regarding available interventions specifically targeting this vulnerable population. This review underscores the need for research to improve understanding of PWLS families to better support them and capitalize on postbariatric surgery benefits.

Perceptions of patients and medical students towards each other in the setting of patient care-a South African perspective.

INTRODUCTION: South Africa urgently needs more doctors. We examined perceptions of patients and students to provide evidence for optimum student-patient ratios and substantiate solutions for this dilemma. METHODS: We interviewed 118 patients and invited 120 students to complete a self-administered questionnaire from four specialities in an academic hospital in Johannesburg. RESULTS: The total sample size was 238 participants. A total of 91/118 (77%) patients and 78/120 (65%) students were female. Almost all the patients had some level of education, with most patients having received at least a secondary education (71/120). More than half of the students (69/120) were final year students. A third (41/118) of the patients were unaware they were admitted to a teaching hospital. Half of the patients (60/118) thought they had the right to refuse interaction with students. Patients and students preferred smaller groups of between 1-3 and 4-8 students at a bedside tutorial (p < 0.001), although patients preferred smaller groups (1-3) compared with the students (4-8). Majority of patients said they never refused consent to students, while a third of students reported at least up to three patients refusing consent to be examined. The most frequent reason cited by students for refusal of consent by patients was the exposure to excessive numbers of students and healthcare professionals. CONCLUSION: Medical schools should consider patient safeguards while responding to the country's need for more doctors. The Medical Council and medical schools need to draw up professional guidelines on patient-student interactions, including the role of patients in this setting.

Interleukin-6 gene polymorhisms and interleukin-6 levels are associated with atherosclerosis in CKD patients.

Inflammation is a major risk factor for atherosclerosis. Genetic polymorphisms in the inflammatory cytokine genes have been associated with atherosclerosis. Because levels of inflammatory cytokines are markedly elevated in patients with chronic kidney disease (CKD), we hypothesized that genotypic variations in the interleukin-6 (IL-6) gene are a cause of systemic inflammatory states and atherosclerosis in South African CKD patients. 120 CKD patients and 40 healthy controls were included. Serum IL-6 and high-sensitivity C-reactive protein (hs-CRP) levels were measured. Functional polymorphisms in the IL-6 genes were genotyped using polymerase chain reaction-sequence specific primer (PCR-SSP) methods. Carotid intima-media thickness (CIMT) and the presence of plaque were assessed by B-mode ultrasonography. Serum IL-6 and hs-CRP levels were increased in patients with CKD compared with healthy controls (p < 0.001). In CKD patients, serum IL-6 above the median value was associated with carotid plaque (OR: 2.11; 95% CI: 1.74 - 2.57, p = 0.004), with excess risk confined to the group with high IL-6 levels. Significant associations were found between the IL-6 gene and atherosclerosis in the CKD group (for G/G genotype: OR = 1.21, 95% CI = 1.05 - 1.39, p = 0.012; for GG+GC vs. CC: OR = 1.14, 95% CI = 1.02 - 1.28, p = 0.035). Patients with GG+GC genotype of the IL-6 gene polymorphism had higher levels of IL-6 than those with CC genotype (p = 0.029). In South African CKD patients, the IL-6 gene promoter polymorphism is associated with high serum IL-6 levels and atherosclerosis. The relationship between atherosclerosis and -174G/C polymorphism in the IL-6 gene suggests that IL-6 may be a potential pro-inflammatory mediator of atherosclerosis in CKD patients.

Parenting after Weight Loss Surgery: A Conceptual Model and Two Case Reports.

The ways families approach eating, shape, and weight can result in stress for individual family members and challenge the overall functioning of the family. This is further complicated among families with a parent who has history of obesity or undergone weight loss surgery (WLS). Although WLS can positively impact other family members, it can also exacerbate conflicts regarding feeding and weight. Such conflicts can involve uncertainty regarding the extent to which the entire family should make the dietary changes recommended for the post-WLS parent. Conflict might also center on the appropriate level of concern regarding the children's risk of developing (or maintaining) obesity. This paper uses two case examples to describe the application of a specialized, time-limited intervention: Parent-Based Prevention following Bariatric Surgery (PBP-B). The program was developed to address the unique challenges and concerns that arise after, or are exacerbated by, WLS. Each detailed case example illustrates a common child-feeding challenge and the employment of key PBP-B strategies throughout the course of treatment. In the first case, the parent who had undergone WLS believed the family's current eating behaviors were the same as those that had led to her own overeating, obesity, and co-occurring psychiatric symptoms, while her husband disagreed. In the second case, both parents were concerned about their son's weight, yet due to their prior eating histories, they felt unable to construct boundaries around the feeding experience. Both cases follow families through the entire intervention and illustrate key points and challenges. These cases underscore the need for novel treatment modalities to support families following parental WLS.

Las maneras en las que las familias abordan la alimentación, la figura y el peso pueden causar estrés en los integrantes individuales de la familia y poner a prueba el funcionamiento general de la familia. Esto es aun más complicado entre las familias con un padre que tiene antecedentes de obesidad o que se sometió a una cirugía para adelgazar. Aunque la cirugía para adelgazar puede repercutir de manera positiva en otros miembros de la familia, también puede exacerbar conflictos con respecto a la alimentación y al peso. Dichos conflictos pueden consistir en la incertidumbre con respecto al grado en el cual toda la familia debería hacer los cambios alimentarios recomendados para el padre que se ha operado para adelgazar. El conflicto también podría centrarse en el nivel adecuado de preocupación en relación con el riesgo de los niños de desarrollar (o mantener) la obesidad. Este artículo utiliza dos ejemplos de casos para describir la aplicación de una intervención especializada y limitada temporalmente: "La prevención basada en los padres después de una cirugía bariátrica" (Parent-Based Prevention following Bariatric Surgery, PBP-B). El programa se desarrolló para abordar los desafíos y las preocupaciones particulares que surgen después de la cirugía para adelgazar o que son exacerbados por esta. Cada ejemplo de un caso detallado ilustra un desafío común con respecto a la alimentación de los niños y al empleo de estrategias fundamentales de la PBP-B a lo largo del transcurso del tratamiento. En el primer caso, la madre que se había sometido a la cirugía para adelgazar creía que los comportamientos alimentarios actuales de la familia eran los mismos que los que la habían conducido a su propia sobreingesta, obesidad, y síntomas psiquiátricos concomitantes, mientras que su esposo no estaba de acuerdo. En el segundo caso, ambos padres estaban preocupados acerca del peso de su hijo, sin embargo, debido a sus antecedentes alimentarios previos, se sentían incapaces de establecer límites en torno a la experiencia alimentaria. Ambos casos siguen a las familias durante toda la intervención e ilustran puntos clave y desafíos. Estos casos subrayan la necesidad de incorporar modalidades innovadoras de tratamiento orientadas a apoyar a las familias después de la cirugía para adelgazar de uno de los padres.