Prenatal depressive symptoms are associated with altered structural brain networks in infants and moderated by infant sleep.

BACKGROUND: The prevalence of prenatal depressive symptoms has more than doubled during the COVID-19 pandemic, raising substantial concerns about child outcomes including sleep problems and altered brain development. The objective of this work was to determine relationships between prenatal depressive symptoms, infant brain network structure, and infant sleep. METHODS: Pregnant individuals were recruited as part of the Pregnancy during the Pandemic (PdP) study. Maternal depressive symptoms were measured in pregnancy and postpartum. When infants of those participants were 3 months of age (n=66; 26 females), infants underwent diffusion magnetic resonance imaging and infant sleep was evaluated. Using tractography, we calculated structural connectivity matrices for the default mode (DMN) and limbic networks. We examined associations between graph theory metrics of infant brain networks and prenatal maternal depressive symptoms, with infant sleep as a moderator. RESULTS: Prenatal depressive symptoms were negatively related to average DMN clustering coefficient and local efficiency in infant brains. Infant sleep duration was related to DMN global efficiency and moderated the relationship between prenatal depressive symptoms and density of limbic connections such that infants who slept less had a more negative relationship between prenatal depressive symptoms and local brain connectivity. CONCLUSIONS: Prenatal depressive symptoms appear to impact early topological development in brain networks important for emotion regulation. In the limbic network, sleep duration moderated this relationship, suggesting sleep may play a role in infant brain network development.

The Evolving Spectrum of Kidney Histology in HIV-Positive Patients in South Africa.

Introduction: Sub-Saharan Africa remains challenged by the highest burden of human immunodeficiency virus (HIV), an epidemic of tuberculosis (TB), and increasing number of people with HIV (PWH) on antiretroviral therapy (ART), all of which may result in kidney injury. Methods: This observational cohort study describes the spectrum of kidney disease in PWH in South Africa, between 2005 and 2020. Kidney biopsies were analyzed in 4 time periods as follows: early ART rollout (2005-2009), tenofovir disoproxil (TDF) introduction (2010-2012), TDF-based fixed dose combination (2013-2015), and ART at HIV diagnosis (2016-2020). Logistic regression was used to identify factors associated with HIV-associated nephropathy or focal segmental glomerulosclerosis (HIVAN/FSGS) and tubulointerstitial disease (TID). Results: We included 671 participants (median age 36, interquartile range, 21-44 years; 49% female; median CD4 cell count 162 [interquartile range, 63-345] cells/mm3). Over time, ART (31%-65%, P < 0.001), rate of HIV suppression (20%-43%, P < 0.001), nonelective biopsies (53%-72%, P < 0.001), and creatinine at biopsy (242-449 µmol/l, P < 0.001) increased. A decrease in HIVAN (45%-29% P < 0.001) was accompanied by an increase in TID (13%-33%, P < 0.001). Granulomatous interstitial nephritis accounted for 48% of TID, mostly because of TB. Exposure to TDF was strongly associated with TID (adjusted odds ratio 2.99, 95% confidence interval 1.89-4.73 P < 0.001). Conclusion: As ART programs intensified and increasingly used TDF, the spectrum of kidney histology in PWH evolved from a predominance of HIVAN in the early ART era to TID in recent times. The increase in TID is likely due to multiple exposures that include TB, sepsis, and TDF as well as other insults.

Outcomes of patients undergoing lung resection for drug-resistant TB and the prognostic significance of pre-operative positron emission tomography/computed tomography (PET/CT) in predicting treatment failure.

Background: Surgery remains an adjunctive treatment for drug-resistant tuberculosis (DR-TB) treatment failure despite the use of bedaquiline. However, there are few data about the role of surgery when combined with newer drugs. There are no outcome data from TB endemic countries, and the prognostic significance of pre-operative PET-CT remains unknown. Methods: We performed a prospective observational study of 57 DR-TB patients referred for surgery at Groote Schuur Hospital between 2010 and 2016. PET-CT was performed if there was nodal disease or disease outside the area of planned resection but did not influence treatment decisions. 24-month treatment success post-surgery (cure or treatment completion), including all-cause mortality, was determined. Findings: 35/57 (61.4%) patients (median age 40 years; 26% HIV-infected) underwent surgery and 22/57 (38.6%) did not (11 patients were deemed unsuitable due to bilateral cavitary disease and 11 patients declined surgery). Treatment failure was significantly lower in those who underwent surgery compared to those eligible but declined surgery [15/35 (43%) versus 11/11 (100%); relative risk 0.57 (0.42-0.76); p < 0.01). In patients treated with surgery, a post-operative regimen containing bedaquiline was associated with a lower odds of treatment failure [OR (95%CI) 0.06 (0.00-0.48); p = 0.007]. Pre-operative PET-CT (n = 25) did not predict treatment outcome. Interpretation: Resectional surgery for DR-TB combined with chemotherapy was associated with significantly better outcomes than chemotherapy alone. A post-operative bedaquiline-containing regimen was associated with improved outcome; however, this finding may have been confounded by higher use of bedaquiline and less loss to follow-up in the surgical group. However, PET-CT had no prognostic value. These data inform clinical practice in TB-endemic settings. Funding: This work was supported by the South African MRC (RFA-EMU-02-2017) and the EDCTP (TMA-2015SF-1043 & TMA- 1051-TESAII).

Multimodal brain features at 3 years of age and their relationship with pre-reading measures 1 year later.

Pre-reading language skills develop rapidly in early childhood and are related to brain structure and functional architecture in young children prior to formal education. However, the early neurobiological development that supports these skills is not well understood. Here we acquired anatomical, diffusion tensor imaging (DTI) and resting state functional MRI (rs-fMRI) from 35 children at 3.5 years of age. Children were assessed for pre-reading abilities using the NEPSY-II subtests 1 year later (4.5 years). We applied a data-driven linked independent component analysis (ICA) to explore the shared co-variation of gray and white matter measures. Two sources of structural variation at 3.5 years of age demonstrated relationships with Speeded Naming scores at 4.5 years of age. The first imaging component involved volumetric variability in reading-related cortical regions alongside microstructural features of the superior longitudinal fasciculus (SLF). The second component was dominated by cortical volumetric variations within the cerebellum and visual association area. In a subset of children with rs-fMRI data, we evaluated the inter-network functional connectivity of the left-lateralized fronto-parietal language network (FPL) and its relationship with pre-reading measures. Higher functional connectivity between the FPL and the default mode and visual networks at 3.5 years significantly predicted better Phonological Processing scores at 4.5 years. Together, these results suggest that the integration of functional networks, as well as the co-development of white and gray matter brain structures in early childhood, support the emergence of pre-reading measures in preschool children.

Retrospective Review of ART Regimens in HIV-Positive to HIV-Positive Kidney Transplant Recipients.

Introduction: The management of complex interactions between antiretroviral therapy (ART) and calcineurin inhibitor (CNI) immunosuppression regimens in HIV-positive to HIV-positive renal transplant recipients can be challenging. Literature describing ART regimens and indications for regimen switching in these patients is limited. Methods: This retrospective review included 53 HIV-positive to HIV-positive renal transplant recipients. Data on ART regimens, reasons for ART switching, and timing of switches were described from day of transplant to study endpoint (end of study date, death, or graft failure). The association between rejection and ART regimen (protease inhibitor [PI] -based vs. non-PI-based regimen) was analyzed using negative binomial regression. Results: There were a total of 46 switches in 31 of 53 patients (58%). Protocol switches (n = 17 of 46, 37%) accounted for most switches, of which the majority were from non-nucleoside reverse transcriptase inhibitors (NNRTIs) to PIs. Other common reasons for switching include cytochrome P450 enzyme induction from efavirenz (EFV) (9 of 46, 20%), tenofovir disoproxil fumarate (TDF) nephrotoxicity (8 of 46, 17%) or side effects (6 of 46, 13%). Of the 46 switches, nearly half (n = 21, 46%) occurred during the transplant admission period, and approximately two-thirds (n = 28, 62%) were during the first year post-transplantation. There was an association between rejection and being maintained on a PI-based regimen (incidence rate ratio 2.77 (95% confidence interval 1.03-7.48), P = 0.044). Conclusion: Despite frequent switching of ART regimens, HIV viral loads remained supressed and graft function remained stable in most HIV-positive kidney transplant recipients in our cohort. There was however a concerning signal for increased rejection rates in those on a PI-based regimen.

The use of brachiobasilic arteriovenous fistulae for haemodialysis: a single-centre descriptive study.

AIM: The main aim of the study was to report on our local experience with the use of brachiobasilic arteriovenous fistulae (BBAVF) and to encourage wider local acceptance of the procedure in accordance with international guidelines. The primary aim was to report on access patency. The secondary aims were to report on functional outcomes and complications. METHODS: This was a retrospective, descriptive study of 41 consecutive haemodialysis patients who underwent BBAVF creation. RESULTS: The primary patency rates at 30 days, and one and three years were 95.1, 48.8 and 19.5%, respectively. Assisted primary patency rates at 30 days, and one and three years were 100, 67.7 and 24.3%, respectively. Secondary patency rates at 30 days, and one and three years were 100, 70.3 and 27%, respectively. CONCLUSION: BBAVF creation can successfully be performed in a resource-constrained environment by surgeons with limited prior experience with the technique. However, careful monitoring, well-established referral pathways for dysfunctional fistulae and access to surgical and endovascular revision seem to be key factors in ensuring long-term patency.

Prenatal Maternal Distress During the COVID-19 Pandemic and Associations With Infant Brain Connectivity.

BACKGROUND: The COVID-19 pandemic has caused substantially elevated distress in pregnant individuals, which has the potential to affect the developing infant brain. Our main objective was to understand how prenatal distress was related to infant brain structure and function and whether social support moderated the associations. METHODS: The Pregnancy during the COVID-19 Pandemic (PdP) cohort study collected Patient-Reported Outcomes Measurement Information System Anxiety scale, Edinburgh Postnatal Depression Scale, and Social Support Effectiveness Questionnaire data from a population-based sample of pregnant individuals living in Canada (N = 8602). For a subsample of participants, their infants (n = 75) underwent magnetic resonance imaging at 3 months of age to examine whether prenatal maternal distress was associated with infant brain architecture, including the role of social support as a potential protective factor. RESULTS: Overall, 33.4% of participants demonstrated clinically elevated depression symptoms and 47.1% of participants demonstrated clinically elevated anxiety symptoms. We identified lower social support as a significant predictor of clinically elevated prenatal maternal distress (t8598 = -22.3, p < .001). Fifty-eight diffusion image datasets (20 female/38 male, 92 ± 14 days old) and 41 functional datasets (13 female/28 male, 92 ± 14 days old) were included in our analysis after removal of poor-quality images and infants without postpartum maternal distress scores. We found significant relationships between prenatal maternal distress and infant amygdala-prefrontal microstructural and functional connectivity measures, and we demonstrate for the first time that social support moderates these relationships. CONCLUSIONS: Our findings suggest a potentially long-lasting impact of the COVID-19 pandemic on children and show that social support acts as a possible mediator not just for pregnant individuals but also developing infants. These findings provide timely evidence to inform clinical practice and policy surrounding the care of pregnant individuals and highlight the importance of social support.

Clinically contextualised ECG interpretation: the impact of prior clinical exposure and case vignettes on ECG diagnostic accuracy.

BACKGROUND: ECGs are often taught without clinical context. However, in the clinical setting, ECGs are rarely interpreted without knowing the clinical presentation. We aimed to determine whether ECG diagnostic accuracy was influenced by knowledge of the clinical context and/or prior clinical exposure to the ECG diagnosis. METHODS: Fourth- (junior) and sixth-year (senior) medical students, as well as medical residents were invited to complete two multiple-choice question (MCQ) tests and a survey. Test 1 comprised 25 ECGs without case vignettes. Test 2, completed immediately thereafter, comprised the same 25 ECGs and MCQs, but with case vignettes for each ECG. Subsequently, participants indicated in the survey when last, during prior clinical clerkships, they have seen each of the 25 conditions tested. Eligible participants completed both tests and survey. We estimated that a minimum sample size of 165 participants would provide 80% power to detect a mean difference of 7% in test scores, considering a type 1 error of 5%. RESULTS: This study comprised 176 participants (67 [38.1%] junior students, 55 [31.3%] senior students, 54 [30.7%] residents). Prior ECG exposure depended on their level of training, i.e., junior students were exposed to 52% of the conditions tested, senior students 63.4% and residents 96.9%. Overall, there was a marginal improvement in ECG diagnostic accuracy when the clinical context was known (Cohen's d = 0.35, p < 0.001). Gains in diagnostic accuracy were more pronounced amongst residents (Cohen's d = 0.59, p < 0.001), than senior (Cohen's d = 0.38, p < 0.001) or junior students (Cohen's d = 0.29, p < 0.001). All participants were more likely to make a correct ECG diagnosis if they reported having seen the condition during prior clinical training, whether they were provided with a case vignette (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.24-1.71) or not (OR 1.58, 95% CI 1.35-1.84). CONCLUSION: ECG interpretation using clinical vignettes devoid of real patient experiences does not appear to have as great an impact on ECG diagnostic accuracy as prior clinical exposure. However, exposure to ECGs during clinical training is largely opportunistic and haphazard. ECG training should therefore not rely on experiential learning alone, but instead be supplemented by other formal methods of instruction.

Utility of mobile learning in Electrocardiography.

Aims: Mobile learning is attributed to the acquisition of knowledge derived from accessing information on a mobile device. Although increasingly implemented in medical education, research on its utility in Electrocardiography remains sparse. In this study, we explored the effect of mobile learning on the accuracy of electrocardiogram (ECG) analysis and interpretation. Methods and results: The study comprised 181 participants (77 fourth- and 69 sixth-year medical students, and 35 residents). Participants were randomized to analyse ECGs with a mobile learning strategy [either searching the Internet or using an ECG reference application (app)] or not. For each ECG, they provided their initial diagnosis, key supporting features, and final diagnosis consecutively. Two weeks later, they analysed the same ECGs, without access to any mobile device. ECG interpretation was more accurate when participants used the ECG app (56%), as compared to searching the Internet (50.3%) or neither (43.5%, P = 0.001). Importantly, mobile learning supported participants in revising their initial incorrect ECG diagnosis (ECG app 18.7%, Internet search 13.6%, no mobile device 8.4%, P < 0.001). However, whilst this was true for students, there was no significant difference amongst residents. Internet searches were only useful if participants identified the correct ECG features. The app was beneficial when participants searched by ECG features, but not by diagnosis. Using the ECG reference app required less time than searching the Internet (7:44 ± 4:13 vs. 9:14 ± 4:34, P < 0.001). Mobile learning gains were not sustained after 2 weeks. Conclusion: Whilst mobile learning contributes to increased ECG diagnostic accuracy, the benefits were not sustained over time.

Kidney Transplantation in HIV-positive Patients: Current Practice and Management Strategies.

BACKGROUND: HIV-positive patients had been successfully transplanted for the last 15 y and the donor pool had successfully been expanded to also include HIV-positive donors. METHODS: We aimed to evaluate the effectiveness of transplantation in HIV-positive patients and highlight some of the important issues reported in the literature. We pooled clinical data from different cohorts to show some of the common issues encountered in HIV-positive transplantation. Furthermore, we searched MEDLINE via PubMed, EMBASE, Cochrane CENTRAL to create a comprehensive table for current evidence for different issues currently encountered when transplanting HIV-positive patients. RESULTS: We included data from 19 cohort studies and reported on outcomes of the current HIV-positive transplant programs. We made recommendations based on personal experience as well as the experience reported in the literature regarding rejection, opportunistic infection, and HIV-associated nephropathy. Opportunistic infections and malignancies are not a major problem for this population group. CONCLUSIONS: HIV-positive patients encounter very specific issues after transplantation, specifically related to drug interactions and higher rejection rates. When utilizing HIV-positive donors, the recurrence of HIV-associated nephropathy in the graft kidney is an issue which can be important. Despite some issues with high rejection rates, HIV-positive patients have similar results to HIV-negative patients posttransplantation.

Effectiveness of blended learning versus lectures alone on ECG analysis and interpretation by medical students.

BACKGROUND: Most medical students lack confidence and are unable to accurately interpret ECGs. Thus, better methods of ECG instruction are being sought. Current literature indicates that the use of e-learning for ECG analysis and interpretation skills (ECG competence) is not superior to lecture-based teaching. We aimed to assess whether blended learning (lectures supplemented with the use of a web application) resulted in better acquisition and retention of ECG competence in medical students, compared to conventional teaching (lectures alone). METHODS: Two cohorts of fourth-year medical students were studied prospectively. The conventional teaching cohort (n = 67) attended 4 hours of interactive lectures, covering the basic principles of Electrocardiography, waveform abnormalities and arrhythmias. In addition to attending the same lectures, the blended learning cohort (n = 64) used a web application that facilitated deliberate practice of systematic ECG analysis and interpretation, with immediate feedback. All participants completed three tests: pre-intervention (assessing baseline ECG competence at start of clinical clerkship), immediate post-intervention (assessing acquisition of ECG competence at end of six-week clinical clerkship) and delayed post-intervention (assessing retention of ECG competence 6 months after clinical clerkship, without any further ECG training). Diagnostic accuracy and uncertainty were assessed in each test. RESULTS: The pre-intervention test scores were similar for blended learning and conventional teaching cohorts (mean 31.02 ± 13.19% versus 31.23 ± 11.52% respectively, p = 0.917). While all students demonstrated meaningful improvement in ECG competence after teaching, blended learning was associated with significantly better scores, compared to conventional teaching, in immediate (75.27 ± 16.22% vs 50.27 ± 17.10%, p <  0.001; Cohen's d = 1.58), and delayed post-intervention tests (57.70 ± 18.54% vs 37.63 ± 16.35%, p <  0.001; Cohen's d = 1.25). Although diagnostic uncertainty decreased after ECG training in both cohorts, blended learning was associated with better confidence in ECG analysis and interpretation. CONCLUSION: Blended learning achieved significantly better levels of ECG competence and confidence amongst medical students than conventional ECG teaching did. Although medical students underwent significant attrition of ECG competence without ongoing training, blended learning also resulted in better retention of ECG competence than conventional teaching. Web applications encouraging a stepwise approach to ECG analysis and enabling deliberate practice with feedback may, therefore, be a useful adjunct to lectures for teaching Electrocardiography.

Determining electrocardiography training priorities for medical students using a modified Delphi method.

BACKGROUND: Although electrocardiography is considered a core learning outcome for medical students, there is currently little curricular guidance for undergraduate ECG training. Owing to the absence of expert consensus on undergraduate ECG teaching, curricular content is subject to individual opinion. The aim of this modified Delphi study was to establish expert consensus amongst content and context experts on an ECG curriculum for medical students. METHODS: The Delphi technique, an established method of obtaining consensus, was used to develop an undergraduate ECG curriculum. Specialists involved in ECG teaching were invited to complete three rounds of online surveys. An undergraduate ECG curriculum was formulated from the topics of ECG instruction for which consensus (i.e. ≥75% agreement) was achieved. RESULTS: The panellists (n = 131) had a wide range of expertise (42.8% Internal Medicine, 22.9% Cardiology, 16% Family Medicine, 13.7% Emergency Medicine and 4.6% Health Professions Education). Topics that reached consensus to be included in the undergraduate ECG curriculum were classified under technical aspects of performing ECGs, basic ECG analysis, recognition of the normal ECG and abnormal rhythms and waveforms and using electrocardiography as part of a clinical diagnosis. This study emphasises that ECG teaching should be framed within the clinical context. Course conveners should not overload students with complex and voluminous content, but rather focus on commonly encountered and life-threatening conditions, where accurate diagnosis impacts on patient outcome. A list of 23 "must know" ECG diagnoses is therefore proposed. CONCLUSION: A multidisciplinary expert panel reached consensus on the ECG training priorities for medical students.

Longitudinal changes of brain microstructure and function in nonconcussed female rugby players.

OBJECTIVE: To longitudinally assess brain microstructure and function in female varsity athletes participating in contact and noncontact sports. METHODS: Concussion-free female rugby players (n = 73) were compared to age-matched (ages 18-23) female swimmers and rowers (n = 31) during the in- and off-season. Diffusion and resting-state fMRI (rs-fMRI) measures were the primary outcomes. The Sports Concussion Assessment Tool and head impact accelerometers were used to monitor symptoms and impacts, respectively. RESULTS: We found cross-sectional (contact vs noncontact) and longitudinal (in- vs off-season) changes in white matter diffusion measures and rs-fMRI network connectivity in concussion-free contact athletes relative to noncontact athletes. In particular, mean, axial, and radial diffusivities were increased with decreased fractional anisotropy in multiple white matter tracts of contact athletes accompanied with default mode and visual network hyperconnectivity (p < 0.001). Longitudinal diffusion changes in the brainstem between the in- and off-season were observed for concussion-free contact athletes only, with progressive changes observed in a subset of athletes over multiple seasons. Axial diffusivity was significantly lower in the genu and splenium of the corpus callosum in those contact athletes with a history of concussion. CONCLUSIONS: Together, these findings demonstrate longitudinal changes in the microstructure and function of the brain in otherwise healthy, asymptomatic athletes participating in contact sport. Further research to understand the long-term brain health and biological implications of these changes is required, in particular to what extent these changes reflect compensatory, reparative, or degenerative processes.

Does social support effect knowledge and diabetes self-management practices in older persons with Type 2 diabetes attending primary care clinics in Cape Town, South Africa?

BACKGROUND: In South Africa with one of the most rapidly ageing populations in Africa despite the demographic impact of the HIV/AIDS epidemic, diabetes is a major cause of morbidity and mortality. Self-management is challenging for all those with the condition but is likely to create a higher demand for those who may have existing co-morbidities associated with age, and long-standing chronic diseases. OBJECTIVE: To determine the relationship of social support, especially that of family and friends with their self-management. METHODS: This cross-sectional study was undertaken in the Cape Town metropole primary care clinics. The sample comprised 406 people drawn from four community health centres (CHC) that are served by Groote Schuur Hospital at the tertiary level. RESULTS: Of the 406 participants, 68.5% were females, 60.5% were living with a family member, and almost half were married. The mean duration of diabetes from diagnosis was eight years. More than half (57.4%) had no or only primary education. Half the participants (50.2%) had poor knowledge level in relation to symptoms and complications of diabetes. Multivariable linear regression showed older age was associated with poor knowledge (®: -1.893, 95% CI-3.754; -0.031) and higher income was associated with self-management practice (®: 3.434, 95% CI 0.797; 6.070). Most participants received family support to follow aspects of diabetes self-management. The ordinal logistic regression indicated that family support was positively associated with the self-management practice score for following a diabetic meal plan, taking care of feet, physical activity, testing blood sugar and handling participants' feelings about being diabetic, but not for taking medication. CONCLUSIONS: Consideration needs to be given to developing and testing education programmes that focus on needs of older people with diabetes and emphases the role of family and friends.

Colonisation with pathogenic drug-resistant bacteria and Clostridioides difficile among residents of residential care facilities in Cape Town, South Africa: a cross-sectional prevalence study.

Background: Residential care facilities (RCFs) act as reservoirs for multidrug-resistant organisms (MDRO). There are scarce data on colonisation with MDROs in Africa. We aimed to determine the prevalence of MDROs and C. difficile and risk factors for carriage amongst residents of RCFs in Cape Town, South Africa. Methods: We performed a cross-sectional surveillance study at three RCFs. Chromogenic agar was used to screen skin swabs for methicillin-resistant S. aureus (MRSA) and stool samples for extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E). Antigen testing and PCR was used to detect Clostridiodes difficile. Risk factors for colonisation were determined with logistic regression. Results: One hundred fifty-four residents were enrolled, providing 119 stool samples and 152 sets of skin swabs. Twenty-seven (22.7%) stool samples were positive for ESBL-E, and 13 (8.6%) residents had at least one skin swab positive for MRSA. Two (1.6%) stool samples tested positive for C. difficile. Poor functional status (OR 1.3 (95% CI, 1.0-1.6)) and incontinence (OR 2.9 (95% CI, 1.2-6.9)) were significant predictors for ESBL-E colonisation. MRSA colonization appeared higher in frail care areas (8/58 v 5/94, p = 0.07). Conclusions: There was a relatively high prevalence of colonisation with MDROs, particularly ESBL-E, but low C. difficile carriage, with implications for antibiotic prescribing and infection control practice.

The effects of add-on corticosteroids on renal outcomes in patients with biopsy proven HIV associated nephropathy: a single centre study from South Africa.

BACKGROUND: The aim of this study was to assess, the efficacy and safety of add-on corticosteroids to antiretroviral therapy [ART] in patients with biopsy proven HIV associated nephropathy. METHODS: All included patients had histological evidence of either collapsing or non-collapsing focal segmental glomerulosclerosis (FSGS) or podocyte and/or parietal cell hypertrophy or hyperplasia. All patients had evidence of tubulointerstitial inflammation with microcysts. Patients were randomized to ART with the addition of 1 mg/kg of corticosteroids [ART+C] or remained in the group [ART Alone] and followed for 2 years. A repeat biopsy was performed at 6 months. RESULTS: Twenty-one patients were randomized to [ART+C] and 17 to [ART Alone]. The baseline estimated glomerular filtration rate (eGFR) was significantly lower in the [ART+C] vs. [ART Alone] group [35mls/min/1.73m2 vs. 47 mls/min/1.73m2, p = 0.015]. The [ART+C] cohort had a statistically significant improvement in median (eGFR) from baseline to last follow up compared with [ART Alone] i.e. [Δ = 25mls/min (IQR: 15;51) vs 9 mls/min (IQR: 0-24), p = 0.008]. There were no statistically significant differences between the groups when proteinuria and histology were analyzed. There were 8 deaths during the trial period, 7 from [ART+C] (Log rank p = 0.071). CONCLUSIONS: In the [ART+C] cohort there was a significant improvement in eGFR over 2-years with increased mortality. Routine corticosteroid use cannot currently be recommended. Further investigation to define which subgroup of this cohort would safely benefit from the positive effects is required. TRIAL REGISTRATION: ISRCTN study ID ( 56112439 ] was retrospectively registered on the 5 September 2018.

Granulomatous interstitial nephritis on renal biopsy in human immunodeficiency virus positive patients: Prevalence and causes in Cape Town, South Africa.

South Africa continues to be burdened by human immunodeficiency virus (HIV) and tuberculosis (TB). In Cape Town, the epidemic of HIV-TB co-infection is as high as 70%. Granulomatous interstitial nephritis (GIN) has increased in frequency on renal biopsy. This study aimed to determine GIN prevalence and causes in HIV-positive patients as well as renal outcomes, patient survival and associated factors. This observational cohort study reviewed HIV-positive renal biopsies for GIN from 2005 to 2012. Causes of GIN (medications, TB, fungal and other), and baseline characteristics were analysed. A comparison of baseline data, renal function and survival was made between GIN and non-GIN cohorts. There were 45/316 biopsies demonstrating GIN. TB was the likely cause of GIN in 27 (60%) and 9 (20%) were due to a drug. Low estimated glomerular filtration rate was a statistically significant factor associated with mortality in both GIN (P = 0.045) and non-GIN cohorts (P < 0.000). In the GIN group, there were 12 (26.7%) deaths. Mortality for all patients was greatest in the first 6 months (P = 0.057). TB co-infection in both cohorts was associated with a higher mortality. The multivariate logistic regression demonstrated that a higher urine protein/creatinine ratio (uPCR) and lower estimated glomerular filtration rate were statistically associated with death. GIN is common in HIV-positive renal biopsies in Cape Town. TB-GIN was the commonest cause and associated with a high early mortality. GIN should be considered in HIV-positive patients with acute kidney injury, its presence conveys a survival benefit. There is a need for improved diagnostic accuracy and treatment strategies of TB-GIN.

Outcomes and challenges of a kidney transplant programme at Groote Schuur Hospital, Cape Town: A South African perspective.

INTRODUCTION: Access to dialysis and transplantation in the developing world remains limited. Therefore, optimising renal allograft survival is essential. This study aimed to evaluate clinical outcomes and identify poor prognostic factors in the renal transplant programme at Groote Schuur Hospital [GSH], Cape Town. . METHOD: Data were collected on all patients who underwent a kidney transplant at GSH from 1st July 2010 to the 30 June 2015. Analyses were performed to assess baseline characteristics, graft and patient survival, as well as predictors of poor outcome. . RESULTS: 198 patients were transplanted. The mean age was 38 +/- 10.5 years, 127 (64.1%) were male, and 86 (43.4%) were of African ethnicity. Deceased donor organs were used for 130 (66.7%) patients and living donors for 65 (33.3%). There were > 5 HLA mismatches in 58.9% of transplants. Sepsis was the commonest cause of death and delayed graft function [DGF] occurred in 41 (21.4%) recipients. Patient survival was 90.4% at 1 year and 83.1% at 5 years. Graft survival was 89.4% at 1 year and 80.0% at 5 years. DGF (HR 2.83 (1.12-7.19), p value = 0.028) and recipient age > 40 years (HR 3.12 (1.26-7.77), p value = 0.014) were predictors of death. CONCLUSION: Despite the high infectious burden, stratified immunosuppression and limited tissue typing this study reports encouraging results from a resource constrained transplant programme in South Africa. Renal transplantation is critical to improve access to treatment of end stage kidney disease where access to dialysis is limited.