Relationships of emerging biomarkers of cancer cachexia with quality of life, appetite, and cachexia.

PURPOSE: Quality of life (QoL), appetite, cachexia, and biomarkers [albumin, hemoglobin (Hb), neutrophils, lymphocytes, platelets, C-reactive protein (CRP), tumor necrosis factor alpha (TNFα), interleukin 6 (IL-6), interleukin 8 (IL-8), C-X-C motif chemokine ligand 5 (CXCL5) and citrullinated histoneH3 (H3Cit)] were compared for 40 cases with advanced cancer and 40 healthy controls. Baseline differences and significant relationships were explored for biomarkers with QoL, appetite, and cachexia. METHODS: In a prospective case-control, age and sex matched study, the European Organisation for the Research and Treatment of Cancer Quality of Life-C30 questionnaire (EORTC-QLQ-C30) for QoL, the Functional Assessment of Anorexia and Cachexia Therapy assessment (FAACT A/CS-12) for appetite, and a five-factor cachexia assessment tool for cachexia assessment were performed. Routine hematological measurements and blood chemistry analyses together with ELISA procedures and a Multiplex® bead array platform, were used for biomarker analysis. Descriptive statistics and regression analyses were undertaken. P < 0.05 defined statistical significance. RESULTS: Global health status (QL-G), functional scales (QL-FS), and symptom scales (QL-SS) differed for cases and controls (p < 0.01). In cases, differences were observed for QL-G (p < 0.01), QL-FS (p < 0.01), and QL-SS (p = 0.01) compared to standardized references values. FAACT A/CS-12 scores differed significantly between cases and controls (p < 0.01) and 30% of cases scored "poor" appetites. Cachexia was present in 60% of cases. Albumin, lymphocytes, platelets, Hb, platelet to lymphocyte ratio (PLR), systemic immune-inflammation index (SII), CRP, TNFα, all at p < 0.01, neutrophil to lymphocyte ratio (NLR) (p = 0.02), IL-6 (p < 0.04), and IL-8 (p = 0.02) differed significantly between cases and controls. No difference was found for CXCL5 or H3Cit. Albumin NLR, Hb, PLR, SII, TNFα, IL-8, and CRP showed significant relationships with all aspects of QoL. QL-FS was significantly related to CXCL5 (p = 0.04), significant relationships with FAACT A/CS-12 included: NLR (p = 0.002), Hb (p < 0.001), and PLR (p < 0.01). NLR, PLR, SII, TNFα, IL-6, IL-8, and CRP correlated positively to cachexia and albumin while Hb and lymphocyte count correlated negatively to cachexia. CONCLUSION: CXCL5 and H3Cit were not reliable biomarkers for cancer cachexia, nor significantly related to QoL, appetite or cachexia. Albumin, NLR, Hb, PLR, SII, TNFα, IL-8, and CRP were reliable indicators of QoL, appetite, and cachexia. Future research should include other novel biomarkers namely growth differentiation factor-15 (GDF-15), fibroblast growth factor 21 (FGF-21), fractakline, interferon gamma (IFN-y), IL-16, macrophage colony stimulating factor (M-CSF), and macrophage procoagulant-inducing factor (MPIF).

Emerging markers of cancer cachexia and their relationship to sarcopenia.

PURPOSE: Emerging biomarkers of cancer cachexia and their roles in sarcopenia and prognosis are poorly understood. Baseline assessments of anthropometrics, sarcopenia, cachexia status and biomarkers of cachexia were measured in patients with advanced cancer and healthy controls. Thereafter, relationships of the biomarkers with cachexia and sarcopenia were explored. METHODS: A prospective case-control design was used, including 40 patients with advanced cancer and 40 gender, age-matched controls. Bioelectrical impedance [skeletal muscle index (SMI)] and hand dynamometry [hand grip strength (HGS)] assessed sarcopenia and a validated tool classified cancer cachexia. Albumin, lymphocyte and platelet counts, haemoglobin, C-reactive protein (CRP), pro-inflammatory cytokines/chemokines and citrullinated histone H3 (H3Cit) were measured. RESULTS: Patients had significantly lower SMI (6.67 kg/m2 versus 7.67 kg/m2, p = < 0.01) and HGS (24.42 kg versus 29.62 kg) compared to controls, with 43% being sarcopenic. Significant differences were found for albumin, lymphocyte and platelet counts, haemoglobin, CRP, and tumour necrosis factor α (TNFα), (p < 0.01). Interleukin (IL)-6 (p < 0.04), IL-8 (p = 0.02), neutrophil/lymphocyte ratio (NLR), p = 0.02, platelet/lymphocyte (PLR) ratio, p < 0.01 and systemic immune inflammatory index (SII), p < 0.01 differed significantly. No difference was observed for CXC motif chemokine ligand 5 [CXCL5 or epithelial neutrophil-activating peptide 78 (ENA78)] or H3Cit. Albumin and haemoglobin correlated negatively with total protein, skeletal muscle mass and SMI (all p < 0.01). The presence of sarcopenia associated significantly with albumin, haemoglobin and CRP. CONCLUSION: Significant relationships and differences of haemoglobin, CRP and albumin supports future use of these biomarkers in cancer cachexia. CXCL5 and H3Cit as valuable biomarkers in cancer cachexia remains to be defined.

Competency Assessment of General Surgery Trainees: A Perspective From the Global South, in a CBME-Naive Context.

OBJECTIVE: Before proceeding with local implementation of competency-based medical education-related assessment practices designed and evaluated in the Global North, we sought to challenge the assumption that this would be perceived as both necessary and acceptable in our context where training and assessment is based on a traditional, knowledge-focused approach. The aim of this study was to determine the perspectives of general surgery trainees and consultants towards the assessment of competence, how this has been achieved previously, and how it should be performed in the future at the University of Cape Town (UCT), South Africa. DESIGN: Semi-structured interviews were conducted with consultants and trainees. Interviews were transcribed and then analyzed using a Reflexive Thematic Analysis approach. SETTING AND PARTICIPANTS: Ten consultants (5 senior and 5 junior) and 10 trainees (5 South African and 5 international) from the Division of General Surgery at UCT in August 2022. RESULTS: Five unique themes were developed: (1) Assessment of competence is essential, (2) competence includes multiple domains of practice, (3) a surgeon must be able to operate, (4) previously used methods were inadequate to assess competence, and (5) frequent assessment with feedback is desired. The themes were considered in the context of Situated Learning Theory, particularly Communities of Practice and their role in the training for, and authentic assessment of, competence in general surgery trainees. CONCLUSIONS: Participants described a need to develop and implement a new competency assessment program for general surgery training in this context, which is aligned with described competency-based medical education principles. Thoughtful integration of the formative and summative use of direct observation in the workplace, with a clear emphasis on procedural ability and the provision of high-quality feedback, may enhance the successful implementation of a strategy for competency-based assessment in general surgery training programs.

Sentinel lymph node biopsy in a resourcelimited setting: a retrospective comparison of sentinel lymph node biopsy before and after the introduction of Sentimag at an academic breast unit.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is performed for staging and prognostication of breast cancer (BC) in cases with a clinically and radiologically negative axilla. Using blue dye and a radioactive colloid injection is considered the gold standard for SLNB. This study aims to evaluate the SLNB outcomes before and after the introduction of Sentimag at an academic breast unit. Sentimag uses an injection of superparamagnetic iron oxide which is then detected in the sentinal lymph node using a magnetometer. METHODS: A retrospective cohort study was performed comparing SLNBs done from 1 January 2017 to 31 December 2018. During 2017, a nuclear medicine technique was used for all SLNBs, while the Sentimag system was used in 2018. RESULTS: There was no difference between the two groups comparing age, T-stage, size of tumour, and molecular status. The only statistically significant difference found was more higher-grade tumours in the group where a nuclear medicine technique was used in 2017 (p = 0.04). There was no difference in the type of surgery performed comparing mastectomy and breast-conserving surgery rates between the two groups. There was an 11% increase in the number of patients who had an SLNB done with the Sentimag technique (2018). In 2017, 42% (58/139) had an SLNB and in 2018, 53% (59/112) had an SLNB. CONCLUSION: This result demonstrates the feasibility of the magnetic technique for SLNB in a resource-limited setting. This new method shows promise as a safe and effective technique for SLNB - it is a valuable alternative in the absence of nuclear medicine (N.Med) facilities.

The impact of thromboelastography on patients with penetrating abdominal trauma requiring intensive care.

BACKGROUND: Trauma-induced coagulopathy (TIC) is a complex multifaceted process which contributes to higher mortality rates in severely injured trauma patients. Thromboelastography (TEG) is effective in detecting TIC which assists in instituting goal-directed therapy as part of damage control resuscitation. METHODS: This retrospective study included all adult patients over a 36-month period with penetrating abdominal trauma who required a laparotomy, blood products and admission for critical care. Analysis included demographics, admission data, 24-hour interventions, TEG parameters and 30-day outcomes. RESULTS: Eighty-four patients with a median age of 28 years were included. The majority (93%; 78/84) suffered from a gunshot injury, with 75% (63/84) receiving a damage control laparotomy. Forty-eight patients (57%) had a TEG. Injury severity score and total fluid and blood product administered in the first 24 hours were all significantly higher in patients who had a TEG (p < 0.05). TEG profiles were: 42% (20/48) normal, 42% (20/48) hypocoagulable, 12% (6/48) hypercoagulable and 4% (2/48) mixed parameters. Fibrinolysis profiles were: 48% (23/48) normal, 44% (21/48) fibrinolysis shutdown and 8% (4/48) hyperfibrinolysis. Mortality rate was 5% (4/84) at 24 hours and 26% (22/84) at 30 days, with no difference between the two groups. High-grade complication rates, days on a ventilator and intensive care unit length of stay were all significantly higher in patients who did not have a TEG. CONCLUSION: TIC is common in severely injured penetrating trauma patients. The usage of a thromboelastogram did not impact on 24-hour or 30-day mortality but did result in a decreased intensive care stay and a decreased high-grade complication rate.

Clinical associations of fetal heart rate accelerations as derived from transabdominal fetal electrocardiograms.

OBJECTIVE: To determine the value of quantifying accelerations of the fetal heart rate (FHR), as collected non-invasively during pregnancy, as a proxy for fetal movements. STUDY DESIGN: The study consists of a prospective collection of research material with retrospective analyses of the collected fetal electrocardiograms (ECGs), done in a homogeneous population in a low socioeconomic residential area of Cape Town, South Africa, as part of the Safe Passage Study. Recruitment and follow-up were done from August 2007 to August 2016. Maternal and fetal ECGs were collected non-invasively at various gestational ages, for approximately 30-60 min at a time in 4418 pregnant women. After processing of the signal, the number and duration of accelerations and the area under the acceleration curve of the FHR were calculated and compared with the pulsatility index (PI) of the uterine, umbilical, and middle cerebral arteries, common medical conditions, tobacco, alcohol, marijuana, and methamphetamine use and z-scores of the birthweight (BWZS). RESULTS: Of the total, 2777, 691, and 3879 women were at gestational ages of 20-24, 28-32 and 34-38 weeks respectively. At 20-24 weeks duration of accelerations was significantly longer in women who used marijuana (p = 0.014) or methamphetamine (p < 0.001) when compared to nonusers. At 28-32 weeks the duration of accelerations was significantly shorter in hypertensive women (p = 0.003) and significantly longer in women who used methamphetamine (p = 0.015). At 34-38 weeks the number of accelerations were significantly less in women who had hypertension ((p = 0.01) or stillbirths (p = 0.028) and the duration significantly shorter in hypertensive women (p = 0.007) and significantly longer in women who used marjuana (p = 0.003) or methamphetamine (p = 0.028). The acceleration area was significantly smaller (p = 0.02) in women who has stillbirths. Duration of accelerations was significantly longer in users of nicotine and alcohol when compared with that of abstainers. Birthweight z-score correlated significantly with number of accelerations (p < 0.01) and the acceleration area (<0.01). There was a significant negative correlation between the number of accelerations (p < 0.01) and acceleration area (p < 0.01) and the PI of the uterine artery at 34-38 weeks. CONCLUSIONS: Calculation of the acceleration parameters of the FHR during pregnancy may provide useful information for evaluating fetal development.

The introduction of competency-based medical education for postgraduate training in South Africa.

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The tragedy of smoking, alcohol, and multiple substance use during pregnancy.

BACKGROUND: Antenatal substance use is a significant public health concern in South Africa (SA). Information on smoking, drinking and drug use during pregnancy was collected prospectively for the Safe Passage Study of the PASS (Prenatal Alcohol in Sudden infant death syndrome and Stillbirth) Network. OBJECTIVES: Data from 4 926 pregnant women in a community near Tygerberg Academic Hospital, Cape Town, were examined to determine whether associations between different substance use groups and postnatal infant outcomes at birth and 1 year were significant. METHODS: Gestational age (GA) was determined by earliest ultrasound. Maternal data were collected at enrolment or first antenatal visit. Substance use data were obtained at up to four occasions. Birthweight data were derived from medical records, and birthweight z-scores (BWZs) were specifically calculated using INTERGROWTH-21st study data. Statistical analyses were done with Statistica version 13.  Results. Women who used more substances enrolled later, were younger, and had smaller mid-upper arm circumferences (MUACs), less education and lower monthly income than women who used no substances (control group). Infants born to women who used more substances had lower GA at delivery, birthweight and BWZ than infants from the control group. At 1 year, infants born to women who used more substances had a lower weight, shorter length and smaller head circumference. Education was positively associated with all infant outcomes at birth and 1 year. MUAC was positively associated with infant BWZ, and weight and length at 1 year. Income was negatively associated with BWZ, but positively associated with all 1-year outcomes. CONCLUSION: Substance use during pregnancy affects infant outcomes at birth and 1 year of age. The addictive properties of substance use make cessation difficult, so prevention strategies should be implemented long before pregnancy. Higher maternal education, associated with better infant outcomes at birth and 1 year and acting as a countermeasure to substance use, is of paramount importance.

Strategies for recovery of a surgical service in the COVID-19 era.

The COVID-19 pandemic has resulted in a massive backlog of elective cases. Delays in the provision of "elective" surgical care have dire consequences for the patient: progression of disease and comorbidities, higher complication rates, and lower overall survival. Delays in elective surgery also have significant consequences for the health system: added emotional strain on healthcare workers, a reduction in training opportunities, increased costs, and increased inequality in health-service provision. As the virus is likely to become endemic, the recovery of surgical services from the initial shock of the first three waves needs to be carefully planned, in order to mitigate the further loss of elective surgical services. This article presents a narrative review of the latest international guidelines and recommendations pertaining to surgical recovery strategies in the COVID-19 pandemic. To begin with, any recovery plan should be led by a local governance committee, who need to design and implement a number of strategies across the three phases of recovery. The preparation phase includes deciding on a system of case prioritisation, assessing and organising resources, and planning innovative ways to reorganise the service itself. The perioperative phase involves putting measures in place to reduce the risk of COVID-19 transmission. The post discharge phase includes the implementation of telemedicine for follow-up, as well as methods of service audit to enable continuous adjustment and improvement. Surgical service recovery presents many challenges; however, these also present a unique opportunity to reassess and improve the efficiency of surgical care delivery.

Association between Increased Uterine Activity, as Recorded Noninvasively from the Anterior Abdominal Wall at 34 Weeks' Gestation, and Preterm Birth.

Background: There is a need to accurately identify pregnant women at risk for preterm birth as early as possible. Recent developments in technology enable the recording of uterine electrical activity (electrohysterogram) from the anterior abdominal wall in a non-invasive way. Objective: To investigate whether uterine activity recorded under resting conditions at a gestational age of 34 weeks could identify a risk of preterm birth. Study design: A commercial antenatal holter device with its dedicated software was used to record and store raw data of the maternal and fetal electrocardiograms and uterine activity for the Safe Passage Study. Uterine activity was recorded under resting conditions from 34 weeks' gestation in epochs of 250 ms (millisecond) for at least 30 min. From this database the raw data, recorded at a mean gestational age of 34 weeks, of 50 women who had preterm deliveries were selected for comparison with data of women who had term deliveries. Mean uterine activity, expressed in microvolt (µV)/epoch, was used for the comparison. Results: After exclusion of 25 participants where labour was induced or augmented and another three for other reasons, 36 remained in each group. The participants in each group were comparable in respect of maternal age, gravidity, parity, gestational age at recruitment and duration of recording. Uterine activity in the preterm group (60.3 µV/epoch) differed significantly (p<0.01) from that of the comparison group (52.4 µV/epoch). Using a cut-off point of 52.3 µV/epoch as obtained from receiver operator characteristic curves (area under the curve 0.72), the sensitivity and specificity of identifying risks of preterm labour were 81% and 50% respectively. Conclusion: Results of this small study are promising but need to be confirmed in larger studies and preferably at earlier gestational age.

Compliance to the South African ventral hernia guidelines: inaugural results from the HIG(SA) registry.

BACKGROUND: The Hernia Interest Group (HIG) of South Africa (SA), following the publication of their inguinal and ventral hernia guidelines (in 2015 and 2016 respectively), developed a hernia registry, the HIG(SA) hernia registry. METHODS: A retrospective analysis of the prospectively maintained HIG(SA) hernia registry from 1 February 2019 to 29 February 2020. Compliance to six recommendations made in the HIG(SA) ventral hernia guidelines were assessed in both the public and private healthcare systems. RESULTS: Three hundred and fifty-three ventral hernia repair cases were included in the study. Fifty-four per cent were private and 46% were public sector cases. Laparoscopic repair for patients with a BMI > 35 kg/m2 occurred in 38% of eligible cases and a minimum 5 cm of mesh overlap was achieved in 50% of cases. Overall, 80% of elective cases occurred in non-smokers; 97% of the intraperitoneal on-lay mesh (IPOM) repairs used composite mesh; 96% of ventral hernias with defects of larger than 2 cm and 95% of incisional hernias were repaired with mesh. Non-smokers undergoing repair numbered 72% in public and 85% in private practice, p = 0.01. CONCLUSION: Ventral hernia repair practices in SA facilities overall had good compliance to four out of the six HIG(SA) ventral hernia guidelines highlighted for the purposes of this study. The two guidelines that had poor compliance overall were 'laparoscopic repair for patients with a BMI of > 35 kg/m2' and 'ensuring a mesh overlap of 5 cm'. The public sector had higher rates of current smokers undergoing elective ventral hernia repair.

Laparoscopic splenopexy for wandering spleen with absorbable mesh fixation.

SUMMARY: Wandering spleen is a rare condition characterised by lack of fixation of the spleen to its usual position in the left upper quadrant. Laparoscopic splenopexy has become the standard of care. Although a number of methods have been described, the use of an absorbable mesh to secure the spleen to the left upper quadrant has been shown to be safe, effective and quick to perform. We present a case of a 32-year-old female with this condition and describe our surgical technique for fixation of the spleen using an absorbable mesh.

Building a national hernia registry in South Africa: initial ventral hernia repair results from a diverse healthcare sector.

PURPOSE: The purpose of this paper was to introduce a new registry in a developing country by describing the demographics, management and 30-day outcomes of patients undergoing ventral hernia repair in the public and private healthcare sectors of South Africa. METHODS: This study was a retrospective review of a prospectively maintained hernia registry from the 1st of February 2019 to 29th of February 2020. RESULTS: 353 ventral hernia repair cases were recorded of which 47% were incisional hernias and the remainder were primary hernias. The median age was 54 years with even distribution of males and females. Half of the patients were obese with a median BMI of 31 kg/m2. The private sector performed 190 cases (54%) and the public sector 163 cases (46%). The public sector had more current smokers undergoing elective repairs, 28% vs 15%, p = 0.01 and performed more emergency repair cases, 21% vs 8%, p < 0.01. The majority (89%) of hernias were repaired with mesh and one-third were repaired laparoscopically. 30 day follow up was obtained in 30% of cases, the private sector had better follow up rates (42% vs 14%). CONCLUSION: Participation in the HIG (SA) registry was low with poor follow up over the first year. Ongoing prospective data capture on the HIG (SA) hernia registry will continue to provide further insights into hernia repair practices in South Africa.

In utero teratogen exposure and cardiometabolic risk in 5-year-old children: a prospective pediatric study.

BACKGROUND: Aorta and carotid intima-media thickness (IMT) is a measure of subclinical atherosclerosis and useful to assess cardiometabolic risk in the young. The in utero milieu may involve cardiometabolic programing and the development of cardiometabolic risk factors in children. Maternal smoking, alcohol consumption, and micronutrient deficiencies during pregnancy influence the development of the cardiovascular system through a process of DNA methylation. AIM: To explore an association between maternal smoking and alcohol consumption during pregnancy and intima media thickness in 5-year-old children for a low-income setting. METHODS: Data were collected from 500 mother-child pairs at antenatal clinic visit, at birth, and at age 5 years. Anthropometric measurements were collected at birth and again at age 5 years. As well as clinical and ultrasound measurements at age 5 years. Clinical measurements, at age 5 years, included blood pressure, mean arterial pressure, and heart rate. Ultrasound measurements of the aorta and carotid arteries IMT were performed at age 5 years. Main outcome of interest was effect of dual teratogen exposure on the ultrasound measures IMT as indication of cardiometabolic risk. RESULTS: cIMT was significantly higher in children exposed to both alcohol and nicotine during pregnancy compared to those not exposed (p = .008). In separate linear models, dual in utero exposure (beta = 0.12; p = .01) and male sex (beta = 0.14; p = .01) were associated with higher right cIMT values (F(6,445) = 5.20; R2 = 0.07, p < .01); male sex (beta = 0.13; p = .01) and low birth weight (beta = 0.07; p = .01) with higher left cIMT value (F(4,491) = 4.49; R2 = 0.04; p = .01); and males sex (beta = 0.11; p = .02) with higher aorta IMT (F(6,459) = 5.63; R2 = 0.07; p < .01). Significant positive correlations between maternal measures of adiposity, maternal MUAC (r = 0.10; p = .03), and maternal BMI (r = 0.12; p < .01) and right cIMT measurements adjusted for the BMI of the child at age 5 years as covariate. Blood pressure measurements at age 5 years were not significantly associated with IMT but, instead, correlated significantly and positively with the BMI of the child at age 5 years (p < .01). CONCLUSION: Children exposed to both maternal smoking and alcohol consumption during pregnancy presented with cardiometabolic risk factors 5 years after birth. In addition, maternal adiposity, male sex, and low birth weight were associated with higher IMT at age 5 years.

The Association between Maternal Depression, Infant Characteristics and Need for Assistance in A Low-Income-Country.

Background: Depression in the peripartum period is prevalent in low-income-countries. The identification of women needing referral is often lacking and on the other hand, women in need of support and treatment do not make use of existing support. Objectives: To identify risk factors for fetal and postnatal consequences of depression in pregnancy and to investigate further management once women at risk have been identified. Methods: The Safe Passage Study was a large prospective multicenter international study. Extensive information, including the Edinburgh postnatal depression scale (EPDS), was collected during the study. At risk women were referred to the study's social worker (SW). Women were categorized according to risk on their EPDS results. Risk categories were characterized and investigated for infant outcomes. Results: Data from 5,489 women were available for analysis and revealed a 51% prevalence of prenatal depression. Fourteen percent of at-risk women attended SW appointments, while 36% accepted the SW referral but persistently failed to attend. At risk women were significantly younger, had less formal education, had lower monthly income, and lived in more crowded conditions. They used significantly more alcohol and cigarettes. Their infants had shorter gestational ages, lower birth weights and were more growth restricted. Infants of depressed women who missed appointments weighed less and were more growth restricted. Conclusion: Women with high EPDSs had less favorable socioeconomic conditions, used more alcohol or tobacco during pregnancy, and their infants weighed less with more growth restriction. Women who repeatedly missed their appointments came from the poorest socioeconomic conditions and their infants had worse birth outcomes.

The effects of in utero exposure to teratogens on organ size: a prospective paediatric study.

In low-income countries, prospective data on combined effects of in utero teratogen exposure are lacking and necessitates new research. The aim of the present study was to explore the effect of in utero teratogen exposure on the size of the kidneys and pancreas 5 years after birth in a low-income paediatric population. Data was collected from 500 mother-child pairs from a low-income setting. Anthropometric measurements included body weight, (BW) body height, mid-upper arm and waist circumference (WC). Clinical measurements included blood pressure (BP), mean arterial pressure and heart rate. Ultrasound measurements included pancreas, and kidney measurements at age 5 years. The main outcome of interest was the effect of maternal smoking and alcohol consumption on ultrasound measurements of organ size at age 5 years. Left and right kidney length measurements were significantly lower in smoking exposed children compared to controls (p = 0.04 and p = 0.03). Pancreas body measurements were significantly lower in smoking exposed children (p = 0.04). Multiple regression analyses were used to examine the associations between the independent variables (IDVs), maternal age, body mass index (BMI), mid-upper arm circumference (MUAC) and BW of the child, on the dependent variables (DVs) kidney lengths and kidney volumes. Also, the association between in utero exposure to alcohol and nicotine and pancreas size. WC was strongest (r = 0.28; p < 0.01) associated with pancreas head [F (4, 454) = 13.44; R2 = 0.11; p < 0.01] and tail (r = 0.30; p < 0.01) measurements at age 5 years, with in utero exposure, sex of the child and BMI as covariates. Kidney length and pancreas body measurements are affected by in utero exposure to nicotine at age 5 years and might contribute to cardiometabolic risk in later life. Also, findings from this study report on ultrasound reference values for kidney and pancreas measurements of children at age 5 years from a low-income setting.

Investigating the threshold for early renal allograft biopsy: A South African single-centre perspective.

BACKGROUND: The most common clinical indication for renal biopsy in the early post-transplant period is early graft dysfunction (EGD), which may present either as delayed graft function (DGF) or acute graft dysfunction. Even though it is a valuable diagnostic tool, renal allograft biopsy is not without risk of major complications. Recent studies have suggested that, with modern immunosuppressive induction regimens and more accurate ways to determine high immunological risk transplants, early acute rejection (AR) is uncommon and routine biopsy for EGD does not result in a change in management. OBJECTIVES: To describe the histological findings and complications of renal allograft biopsies for EGD in our setting, and to determine whether our current threshold for biopsy is appropriate. METHODS: This study was a retrospective audit that included all patients who underwent renal allograft biopsy within the first 30 days of transplantation at Groote Schuur Hospital, Cape Town, South Africa, from 1 June 2010 to 30 June 2018. The indication for biopsy was any patient who showed significant EGD, characterised by acute graft dysfunction or DGF with dialysis dependence. RESULTS: During the study period, 330 patients underwent renal transplantation, of whom 105 (32%) had an early biopsy and were included in the study. The median age of recipients was 39 (range 17 - 62) years, with 65% males and 35% females. The majority of donors were deceased donations after brain death (70%), with an overall median cold ischaemic time of 9 hours (interquartile range (IQR) 4 - 16). The average number of human leukocyte antigen mismatches was 5 (IQR 4 - 7). A donor-specific antibody was recorded for 18% of recipients and a panel-reactive antibody score of >30% was recorded for 21%. The median duration after transplant for biopsy was 8 (IQR 6 - 10) days. During the first month of EGD, AR was diagnosed in 42% of patients who underwent biopsies. In 21% of these patients, there was acute cellular rejection, in 16% antibody-mediated rejection, and in 5% both of these. Acute tubular necrosis was the primary finding in 32%, with acute interstitial nephritis in 8%, and acute calcineurin toxicity in 4% of cases. A significant biopsy-related complication was recorded in 3 patients: 1 small-bowel perforation repaired via laparotomy, and 2 vascular injuries successfully embolised by interventional radiology. CONCLUSIONS: Considering the relative safety and high rate of detection of AR, a liberal approach to renal biopsy for EGD remains justifiable in our setting.

Surgery for Pheochromocytoma: A Single-Center Review of 60 Cases from South Africa.

BACKGROUND: There is a paucity of data on the presentation and surgical management of pheochromocytoma in developing nations, particularly in Africa. METHODS: This study was a retrospective review, which included all patients managed by the Groote Schuur Hospital/University of Cape Town Endocrine Surgery unit for pheochromocytoma and abdominal paragangliomas, from January 2002 to June 2019. RESULTS: Sixty patients were included in the study, of which 33% were male and 67% female. The mean age was 47 years (range 14-81). The median tumor size was 6 cm, with 45% larger than 6 cm. 92% were located in the adrenal gland (87% unilateral, 5% bilateral), and 8% were extra-adrenal. The conversion rate for laparoscopic cases was 20%, with 55% of cases overall completed laparoscopically. Eleven patients with tumors > 6 cm were initially attempted laparoscopically, of which 3 were converted to open, without any associated increased morbidity. A major adverse event was recorded for 5 cases (8%), including 1 mortality. Overall morbidity, blood loss, operating time and hospital stay were all significantly reduced in the laparoscopic group. There were 5 patients with malignant disease (8%). CONCLUSION: This large series, from an established academic endocrine surgery unit in Africa, can serve as a benchmark for units with similar settings and resource limitations, to compare their surgical management and perioperative outcomes.

Smoking and drinking habits of women in subsequent pregnancies after specific advice about the dangers of these exposures during pregnancy.

BACKGROUND: Although women are informed about the dangers of drinking and smoking during pregnancy when they book for antenatal care, it is uncertain whether this advice is accepted, or whether attempts are made to apply it in subsequent pregnancies. OBJECTIVES: To assess how pregnant women respond to the advice to refrain from smoking and drinking during pregnancy in subsequent pregnancies. METHODS: Research staff were trained to obtain accurate prospective information on smoking and drinking during pregnancy in a prospective study, using well-standardised methods. Care was taken to inform participants about the dangers of smoking and drinking during pregnancy. They were also given pamphlets on these dangers in their own language and a list of telephone numbers where they could find help to quit should they need it. This information was repeated at subsequent study visits (ranging from 1 to 3, depending on the gestational age at which they enrolled). Gestational age was determined by early ultrasound. Z-scores of birthweight for gestational age were determined according to the INTERGROWTH-21st study. Pregnancy outcomes of women who enrolled twice (n=888) or three times (n=77) in the Safe Passage Study were compared with those of women in the first enrolment (n=889). RESULTS: The proportion of drinkers did not change significantly (p=0.058) from the first to the second and third enrolments (63.8%, 59.0% and 54.6%, respectively). A similar trend was found for smokers (73.3%, 72.2% and 68.4%, respectively). Cannabis use was reported by 15.1%, 9.7% and 12.0% (p<0.005) of women, respectively, and use of methamphetamine by 10.1%, 6.6% and 12.7% (p<0.005). There was an increase in the rate of preterm births from 15.5% to 17.5% and 24.7%, respectively, but the increase was not significant. Although mean birthweight was lower in the third enrolment compared with the second, the difference was not significant. The z-score of birthweight for gestational age was significantly lower in the second enrolment compared with the first. CONCLUSIONS: Detailed information on the adverse effects of smoking and drinking during pregnancy was not effective in the population studied. Other methods to reduce or stop these toxic exposures should therefore be investigated. A short inter-pregnancy interval, as demonstrated by three enrolments in 7.5 years, is associated with preterm labour and fetal growth restriction, and is probably indicative of the role played by confounders such as poor socioeconomic conditions and drug exposure during pregnancy.

The association of prenatal alcohol exposure on the cognitive abilities and behaviour profiles of 4-year-old children: a prospective cohort study.

OBJECTIVE: To examine the association of prenatal alcohol exposure (PAE) on cognitive abilities and behaviour profiles of 4-year-old children. DESIGN: Prospective cohort study. SETTING: Cape Town, South Africa. POPULATION: A cohort of 500 children. METHODS: Children from the Safe Passage Study, which prospectively collected PAE, were included. Cognition and behavioural profiles were assessed. Children with and without PAE were compared. Mean scores were compared, with P ≤ 0.05 considered significant. Results were adjusted for confounding factors. MAIN OUTCOME MEASURES: The Kaufman Assessment Battery for children measured intellectual and mental ability; the NEPSY-II instrument assessed neurocognitive performance. The caregiver completed the Preschool Child Behaviour checklist to rate the child's problem behaviours and competencies. RESULTS: Two hundred children had no PAE, 117 children had mild to moderate PAE (with no binge episodes), 113 children had heavy PAE (with one or two binge episodes), and 70 children had very heavy PAE (with three or more binge episodes). Women who binge drank had significantly higher rates of smoking, marijuana use, and methamphetamine use. Low to moderate PAE had no effect on cognitive ability and behaviour. Very heavy PAE was associated with problems performing simultaneous as well as sequential functions, lower scores in the language and sensorimotor domain, and more attention and pervasive developmental problems. CONCLUSIONS: Low to moderate PAE was not associated with cognitive processing or developmental problems. Women who had many binge drinking episodes during pregnancy were the most at risk for cognitive processing, neurocognitive, and behaviour problems in their children at 4 years of age. TWEETABLE ABSTRACT: Low to moderate prenatal alcohol use was not associated with cognitive or behavioural problems in 4-year-olds.