Gestational gigantomastia complicated by pseudo-angiomatous stromal hyperplasia - a multidisciplinary management approach.

SUMMARY: Gestational gigantomastia is a rare condition typified by disproportionate bilateral breast enlargement in pregnant women, resulting in skin thinning, ulceration, and bleeding. Less than sixty cases have been documented worldwide, and only one other in South Africa. Pseudo-angiomatous stromal hyperplasia (PASH) is a rare benign proliferation of stromal tissue in a tumorous or diffuse pattern. This, to the best of our knowledge, is the first published case, a 27-year-old human immunodeficiency virus (HIV) positive woman, to present with both conditions concurrently. Medical management with cabergoline was initiated and, seven months post-delivery, a novel Goldilocks mastectomy was performed with acceptable outcomes.

Retroperitoneoscopic adrenalectomy - introducing a new surgical technique in South Africa.

BACKGROUND: Posterior retroperitoneoscopic adrenalectomy (PRA) is purported to be superior to the laparoscopic transperitoneal approach (LA) in patients with a select spectrum of benign adrenal pathologies. Advantages attributed to the technique include minimal blood loss, shortened operative times, and decreased postoperative pain, explained anatomically by the direct access to the adrenal gland. Reduced workspace is a limitation. METHODS: A retrospective review of 22 consecutive PRAs performed in a single centre between 1 September 2016 and 30 October 2020 is presented. Two experienced laparoscopic surgeons operated on all patients after acquiring the technique at international centres. Suitable candidates were carefully pre-selected. Non-benign pathology, high vascularity, body mass index (BMI) ≥ 45 kg/m2 and anatomical concerns on prior computed tomography (CT) imaging were exclusion criteria. RESULTS: Twenty-two PRAs were performed for a spectrum of benign adrenal pathologies. Twenty-one surgeries (95%) were completed. A single case of pheochromocytoma required conversion. The procedure was safe, a minor postoperative complication (pneumaturia) occurred in one case, and the mortality rate was 0%. Median operative time (80 minutes) is comparable to other reported series in the literature, with a modest linear descending tendency noted over the study period. Underlying pathology influenced operative times. Pheochromocytomas proved to be most challenging and required careful preoperative evaluation. CONCLUSION: The PRA procedures performed at Tygerberg Academic Hospital were safe and reproducible in a select group of cases with benign adrenal pathology. Endocrine surgeons proficient with laparoscopic techniques should be encouraged to use the PRA approach when encountering adrenal neoplasms that fit the criteria.

Premenopausal osteoporosis.

In premenopausal women, bone mineral density measurement by dual-energy X-ray absorptiometry should not be used as the sole guide for diagnosis or treatment of osteoporosis, universal screening with bone mineral density is not advised and the World Health Organization classification of bone status should not be applied. A diagnosis of premenopausal osteoporosis is reserved for those with evidence of fragility and may also be considered in women with low bone mass and an ongoing secondary cause of osteoporosis. Idiopathic osteoporosis in young women is rare. A thorough evaluation of secondary causes is indicated in all patients, with glucocorticoid treatment a common secondary cause of low bone mass and osteoporosis. Hypoestrogenism may be the primary cause of low bone mass and contribute to excessive bone loss in many conditions associated with premenopausal osteoporosis, and should be treated unless contra-indicated. The mainstay of treatment in premenopausal females with low bone mass includes risk factor reduction, advocating a healthy, active lifestyle and optimal treatment of secondary causes of bone loss. The safety of bone-specific therapy, especially long term and during pregnancy, remains uncertain. Bisphosphonates, teriparatide, denosumab and estrogen treatment increase bone density in premenopausal women with osteoporosis, but there are no study data confirming short-term fracture prevention with use of these agents.

Genetic testing approaches for hereditary breast cancer: Perspectives from a private diagnostic laboratory.

Breast cancer is highly prevalent in South Africa, and up to 10% of breast cancer cases may be hereditary. The landscape of genetic testing options for hereditary breast cancer (HBC) has changed significantly over the past decade, and healthcare providers are faced with multiple options when referring breast cancer patients for genetic testing. We have performed a retrospective study of 3 years' worth of breast cancer genetic testing referrals to our laboratory. While Afrikaner and Ashkenazi Jewish founder screens may be appropriate as first-line tests in a limited subset of patients, we have shown that in the majority of cases it is more effective to adopt a multigene panel approach. While variants in the BRCA1 and BRCA2 genes still account for a significant proportion of cases, close to 40% of pathogenic variants were found in genes other than BRCA1 or BRCA2. There are many factors that healthcare providers should consider when requesting genetic testing for breast cancer patients and families, including family history, ancestral background, cost, medical aid scheme reimbursement and scope of testing. We summarise our findings and provide advantages and disadvantages of each approach, with the aim of assisting clinicians and genetic counsellors to make appropriate testing decisions.

Diabetes mellitus and COVID-19: A review and management guidance for South Africa.

This article reviews the association between diabetes mellitus (DM) and COVID-19. We report on the convergence of infectious diseases such as coronavirus infections and non-communicable diseases including DM. The mechanisms for the interaction between COVID-19 and DM are explored, and suggestions for the management of DM in patients with COVID-19 in South Africa are offered.

Ethnic and gender-specific incidence rates for hip fractures in South Africa: A multi-centre study.

BACKGROUND: Limited data exist on the incidence of hip fractures in South Africa (SA). We report gender and ethnic specific incidence rates of hip fractures in SA. METHODS: In a multicentre prospective study, conducted in geographically defined municipalities of three provinces in SA, a structured questionnaire was administered to all subjects aged 40 years and over, presenting with a new atraumatic hip fracture, from 1 April 2017 to 31 March 2018. Gender and ethnic specific incidence rates (IR) of hip fractures were calculated using population statistics from Statistics SA. FINDINGS: Of the 2767 subjects enrolled, 1914 (69·2%) were women and 853 (30·8%) were men. The majority of subjects were from the White population (40·9%) followed by those from the African (26·4%), Coloured (18·7%) and Indian (13·9%) populations. Men with hip fractures were significantly younger than women in the total group (69 [IQR 59-79] versus 77 years [IQR 68-84], p < 0·001) and in each ethnic group. White subjects were significantly older (p < 0·0001) and Africans significantly younger (p < 0·0001) than the other ethnic groups. In women, the highest IR was noted in the White population (176·0 per 100,000), followed by that in the Indian (147·7 per 100,000), Coloured (73·2 per 100,000) and African populations (43·6 per 100,000). A similar pattern was seen in men albeit at lower rates, with the highest rate in White men at 76·5 per 100,000. In the total study population and the African population, the IR was higher in men compared to women in subjects under 60 years. In the White population, the IR was higher in men compared to women in the 40-44 years age group. While in the Coloured and Indian populations the IR was higher in men compared to women in the 40-49 years and 45-54 years age groups, respectively. There was an increase in the relative risk ratios with age in the total study population, and in all ethnic groups in both women and men. INTERPRETATION: Hip fractures occur in all ethnic groups in South Africa with higher IRs in the White and Indian populations compared to the Coloured and African populations. Consistent with the published literature, the overall hip fracture IR was higher in women than in men, except in the younger age groups, and increased with age. FUNDING: South African Medical Research Council and the University of KwaZulu-Natal Competitive Research Grant.

An audit of thyroid function testing in acutely ill patients at a South African academic hospital.

Background: Non-thyroidal illness syndrome (NTIS) can be defined as the presence of abnormal thyroid function in the absence of primary thyroid dysfunction and is associated with acute illness. Thyroid function testing is generally not advised in the critically ill patient. Thyroid-stimulating hormone (TSH) measurement is the preferred screening test for thyroid disease, but results may be misleading and variable in the setting of critical illness. Objectives: To describe the pattern of requests for TSH testing in patients admitted to the emergency department and intensive care units at Tygerberg Hospital, Cape Town, South Africa. Methods: A retrospective, descriptive (observational) study was conducted over a 6-month period to determine the number of requests for TSH testing received for patients admitted to the emergency department and intensive care units. Results: A total of 1 139 requests for TSH testing were received from the emergency department and intensive care units, of which 166 were excluded. Of the 973 requests evaluated, 14% yielded abnormal results. The majority (79.4%) of the abnormal TSH results were most likely attributed to NTIS. Follow-up TSH results after 6 - 8 weeks were available in only 18% of cases with abnormal TSH levels at initial presentation. Conclusion: We found that TSH testing was often requested in critically ill patients, but that most results were either normal or indicative of NTIS. Follow-up testing of abnormal TSH results was rarely performed. We recommend continued education of junior clinicians regarding thyroid function testing in critically ill patients. Contributions of the study: This study describes the requesting pattern for TSH tests in patients admitted to the emergency department and intensive care unit at Tygerberg Hospital, South Africa. The findings emphasise the importance of prudent thyroid function testing in critically ill patients and follow-up in suspected cases of non-thyroidal illness syndrome.

Diabetes mellitus and COVID-19: A review and management guidance for South Africa

This article reviews the association between diabetes mellitus (DM) and COVID-19. We report on the convergence of infectious diseases such as coronavirus infections and non-communicable diseases including DM. The mechanisms for the interaction between COVID-19 and DM are explored, and suggestions for the management of DM in patients with COVID-19 in South Africa are offered

Preventable warfarin-induced birth defects: A missed opportunity?

BACKGROUND: Congenital abnormalities and pregnancy losses due to the teratogenic effects of warfarin are prevalent among the South African population. These are potentially preventable if the challenges and barriers faced by at-risk women are understood and addressed effectively. OBJECTIVES: To determine the practice, knowledge and attitudes regarding the teratogenic risks experienced by women administered warfarin. METHODS: A descriptive study was performed. Quantitative data were collected through a researcher-administered questionnaire. The target population comprised 101 women of reproductive age who received warfarin treatment and attended a single tertiary-level anticoagulation clinic. RESULTS: Patient-related challenges identified in this study are: language barriers, poor understanding of basic terminology and mathematics, poor contraceptive and family planning practices, lack of knowledge regarding the risks of warfarin in pregnancy and passive attitudes towards information attainment. CONCLUSIONS: Interventions are necessary to address the challenges in such settings. These include increased awareness of the teratogenic potential of specific chronic medications among healthcare providers, patients and the public. Standardised management protocols for women of reproductive age initiated on teratogenic medications should be implemented, including contraceptive and family planning discussions at follow-up visits. Improvement of the counselling skills of healthcare providers and the availability of translators or healthcare providers fluent in local languages could assist in risk reduction.

A comparison between point-of-care testing and venous glucose determination for the diagnosis of diabetes mellitus 6-12 weeks after gestational diabetes.

AIM: To evaluate point-of-care-testing (POCT) for the diagnosis of Type 2 diabetes mellitus 6-12 weeks post-partum in women with gestational diabetes (GDM). METHODS: Post-partum glucose assessment (75-mg oral glucose tolerance test, OGTT) was performed prospectively in 122 women with GDM (1 November 2015 to 1 November 2017) at Tygerberg Hospital, Cape Town, South Africa. Individuals with known pre-existing diabetes were excluded. The accuracy and clinical utility of POCT (capillary finger-prick) were compared with laboratory plasma glucose (hexokinase and glucokinase methods). The OGTT consisted of two time points (fasting and 2 h) during which concurrent glucose samples (POCT and laboratory) were obtained. Bland-Altman plots and paired analysis were used to assess the analytical accuracy of POCT, whereas its diagnostic performance was determined using positive and negative predictive values to calculate specificity and sensitivity. RESULTS: Spearman's ranked correlation analysis indicated a strong association between POCT and laboratory glucose values at both OGTT time points (fasting, r = 0.95, P < 0.0001; 2 h, r = 0.88, P < 0.0001). Thirty-six women were diagnosed with Type 2 diabetes based on gold standard laboratory glucose levels (fasting > 7 mmol/l; 2 h > 11.1 mmol/l). POCT correctly identified Type 2 diabetes in 78% of women (28 of 36) with a positive predictive value of 89.3% and a negative predictive value of 96.7% at the fasting time point. The sensitivity and specificity of POCT to diagnose Type 2 diabetes were 89% (fasting), 85.7% (2 h) and 96.7% (fasting), 98.5% (2 h) respectively. POCT proved less sensitive to diagnose pre-diabetes (69%) but displayed satisfactory specificity (92%) at both time points assessed. CONCLUSION: POCT accurately identifies women with Type 2 diabetes 6-12 weeks after GDM.

DFT and CV data of 4-phenyl-substituted dichloro(bis{2-[1-(phenyl)-1H-1,2,3-triazol-4-yl-κN3]pyridine-κN})iron(II) coordination compounds.

The data presented in this paper are related to the research article entitled "Synthesis, characterisation and electrochemistry of eight Fe coordination compounds containing substituted 2-(1-(4-R-phenyl-1H-1,2,3-triazol-4-yl)pyridine ligands, R=CH3, OCH3, COOH, F, Cl, CN, H and CF3." (Conradie et al., 2019) [1]. This paper presents electrochemical and density functional theory data of 4-phenyl-substituted dichloro(bis{2-[1-(4-R-phenyl)-1H-1,2,3-triazol-4-yl-κN3]pyridine-κN})iron(II) compounds, containing differently substituted 2-(1-(4-R-phenyl)-1H-1,2,3-triazol-1-yl)pyridine ligands (L2 - L9) (Tawfiq et al., 2014) [2]. Density functional theory calculated data of five different structural isomers for each compound, consistently show that the title compounds are octahedral and that the isomer with the chloride atoms, the pyridine nitrogens and the triazol nitrogens trans to each other, has the lowest energy. Natural bonding orbital (NBO) data and quantum theory of atoms in molecules (QTAIM) data of dichloro(bis{2-[1-(phenyl)-1H-1,2,3-triazol-4-yl-κN3]pyridine-κN})iron(II) show origin for the preference of the trans isomer.

Chemical and structural data of (1,2,3-triazol-4-yl)pyridine-containing coordination compounds.

The data presented in this paper are related to the research article entitled "Novel dichloro(bis{2-[1-(4-methylphenyl)-1H-1,2,3-triazol-4-yl-κN3]pyridine-κN})metal(II) coordination compounds of seven transition metals (Mn, Fe, Co, Ni, Cu, Zn and Cd)" (Conradie et al., 2018) [1]. This paper presents characterization and structural data of the 2-(1-(4-methyl-phenyl)-1H-1,2,3-triazol-1-yl)pyridine ligand (L2) (Tawfiq et al., 2014) [2] as well as seven dichloro(bis{2-[1-(4-methylphenyl)-1H-1,2,3-triazol-4-yl-κN3]pyridine-κN})metal(II) coordination compounds, [M(L2)2Cl2], all containing the same ligand but coordinated to different metal ions. The data illustrate the shift in IR, UV/VIS, and NMR (for diamagnetic complexes) peaks when L is coordinated to the metals, as well as the influence of the different metals on the peak positions. Solid state structural data is presented for M = Ni and Zn, while density functional theory calculated energies, structures and optimized coordinates are provided for the lowest energy cis and trans conformations for L2 as well as [M(L2)2Cl2] with M = Mn, Fe, Co, Ni, Cu, Zn and Cd.

Systemic Factors During Metabolic Disease Progression Contribute to the Functional Decline of Adipose Tissue-Derived Mesenchymal Stem Cells in Reproductive Aged Females.

It is known that advanced metabolic disorders such as type 2 diabetes compromise the functional and regenerative capacity of endogenous adipose-tissue resident stem cells (ADSCs). It is, however, still unclear at which stage of disease progression ADSCs become compromised and whether systemic factors contribute to their functional decline. It was therefore hypothesized that inflammatory changes in the systemic microenvironment during distinct stages of disease progression negatively affect the functional capacity of ADSCs. A total of forty-seven (n = 47) black African reproductive aged females (32 ± 8 years; mean ± SD) were included in this study and subdivided into: (a) healthy lean (C; body mass index, BMI ≤ 25 kg/m2), (b) healthy overweight/obese (OB; BMI ≥ 25 kg/m2), (c) obese metabolic syndrome (MetS; BMI ≥ 30 kg/m2), and (d) type 2 diabetes mellitus (T2DM; previously diagnosed and on treatment) groups. Participants underwent anthropometric assessments and a DXA scan to determine their body composition and adipose indices. Each persons' systemic metabolic- (cholesterol, HDL, LDL, triglycerides, and blood glucose) and inflammatory profiles (CRP, SDF1α, TNFα, IL6, IL8, IL10, and IFNy) were also evaluated. Participant-derived serum was then used to treat an ADSC cell line in vitro and its effect on viability (MTT-based assay), proliferation (BrdU), migration (wound healing assay), and osteogenic differentiation assessed. When exposed to serum derived from overweight/obese individuals (with or without metabolic syndrome), both the proliferative and migratory responses of ADSCs were less pronounced than when exposed to healthy control serum. Serum IL6 concentrations were identified as a factor influencing the proliferation of ADSCs, suggesting that long-term disruption to the systemic cytokine balance can potentially disrupt the proliferative responses of ADSCs. Obese participant-derived serum (with and without metabolic syndrome) furthermore resulted in lipid accumulation during osteogenic differentiation. This study, therefore demonstrated that systemic factors in obese individuals, regardless of the presence of metabolic syndrome, can be detrimental to the multifunctional properties of ADSCs.

A Direct Comparison of the Effects of the Antiretroviral Drugs Stavudine, Tenofovir and the Combination Lopinavir/Ritonavir on Bone Metabolism in a Rat Model.

Antiretroviral (ARV) treatment may induce metabolic complications in HIV patients on long-term therapy that can affect bone health. In this study, the effects of the ARVs Stavudine (d4T), Tenofovir (TDF) and Lopinavir/ritonavir (LPV/r) on bone metabolism and lipodystrophy were directly compared in rats to negate the consequences of HIV-associated confounding factors. Healthy 12-14-week-old male Wistar rats (n = 40) were divided into four treatment groups and received an oral animal equivalent dose of either Stavudine (6.2 mg/kg/day), TDF (26.6 mg/kg/day), LPV/r (70.8 mg/kg/day) or water (Control 1.5 mL water/day) for a period of 9 weeks. Whole-body DXA measurements, a biomechanical three-point breaking test and histomorphometric analysis were performed on the femurs and tibias at the end of the treatment period. Stavudine monotherapy was found to be associated with decreased femoral bone mineral density that translated into reduced bone strength, whereas histomorphometric analysis demonstrated that Stavudine induces an imbalance in bone metabolism at tissue level, evident in higher resorption (eroded surfaces, osteoclast surfaces and osteoclast number) and lower formation parameters (osteoblast surfaces and osteoid surfaces). This was less clear in the rats treated with either TDF or LPV/r. Furthermore, both Stavudine and TDF treatment resulted in significant bone marrow adiposity, although no significant redistribution of body fat was noted in the treated rats compared to controls. The data from this study suggest that in the absence of HIV-associated factors, LPV/r is less detrimental to bone metabolism compared to Stavudine and TDF.

Pharmacogenetics of Aromatase Inhibitors in Endocrine Responsive Breast Cancer: Lessons Learnt from Tamoxifen and CYP2D6 Genotyping.

BACKGROUND: Genetics play a significant role in drug metabolism of endocrine therapy of breast cancer. These aspects have been studied extensively in patients on tamoxifen, but the pharmacogenetics of aromatase inhibitors are less established. In contrast to the protective effect of tamoxifen, aromatase inhibitors are linked with an increased risk for bone loss and fractures. OBJECTIVE: This review outlines key issues in the implementation of pharmacogenetics of cytochrome P450 and tamoxifen as a model for optimal use of aromatase inhibitors in postmenopausal women with estrogen receptor positive breast cancer. METHODS: Lessons learnt from the association between tamoxifen and CYP2D6 genotyping were applied to identify polymorphisms with the potential to change clinical decision-making in patients on aromatase inhibitors. The ability of next generation sequencing to supersede single-gene analysis was furthermore evaluated in a subset of breast cancer patients on aromatase inhibitors selected from a central genomics database. RESULTS: Methodological flaws in major randomised controlled trials and continued referral to incorrect results in expert consensus statements are important factors delaying the implementation of CYP2D6 pharmacogenetics in tamoxifen treatment. This highlighted the importance of a clinical pipeline including comprehensive genotyping, to define the target population most likely to benefit from aromatase inhibitor pharmacogenetics. CONCLUSION: The clinical utility of CYP2D6 genotyping is well-established in patients at increased risk of tamoxifen resistance due to cumulative risk. The pharmacogenetics of CYP19A1 requires further clarification in terms of bone risk assessment for appropriate use in the treatment algorithm of high-risk patients at the onset of aromatase inhibitors.

Postmenopausal Breast Cancer, Aromatase Inhibitors, and Bone Health: What the Surgeon Should Know.

Breast cancer, as the most common malignancy in women, remains a major public health issue despite countless advances across decades. Endocrine therapy is the cornerstone of treatment of the hormone-sensitive subtype of breast cancer. The use of aromatase inhibitors (AIs) in the postmenopausal women has extended the survival beyond that of Tamoxifen, but harbors a subset of side effects, most notably accelerated bone loss. This, however, does not occur in all women undergoing treatment. It is vital to identify susceptible patients early, to limit such events, employ early treatment thereof, or alter drug therapy. International trials on AIs, predominantly performed in North American and European females, provide little information on what to expect in women in developing countries. Here, surgeons often prescribe and manage endocrine therapy. The prescribing surgeon should be aware of the adverse effect of the endocrine therapy and be able to attend to side effects. This review highlights clinical and biochemical factors associated with decrease in bone mineral density in an, as yet, unidentified subgroup of postmenopausal women. In the era of personalized medical care, appropriate management of bone health by surgeons based on these factors becomes increasingly important.

Association between low serum free testosterone and adverse prognostic factors in men diagnosed with prostate cancer in KwaZulu-Natal.

BACKGROUND: The association of serum free testosterone (FT) with prostate cancer is not fully understood. Studies on the results of the relationship between serum testosterone level and prostate cancer are conflicting. However, there is a reported association between lower serum testosterone levels and high-grade prostate cancer. OBJECTIVE: To investigate the relationship between serum FT and the clinico-pathological characteristics of prostate cancer in South African patients. MATERIALS AND METHODS: The clinical data of 109 consecutive patients diagnosed with prostate cancer on biopsy were evaluated prospectively. The variables were age, ethnic group, prostate specific antigen (PSA), digital rectal examination (DRE) findings, clinical tumour, nodes and metastases (TNM) stage, and Gleason score. Low serum FT was defined as <250ng/dl. Statistical analysis was performed using Stata V10 software (p<0.05 considered significant). RESULTS: There was a statistically significant association between low serum FT and high serum PSA, high Gleason score and clinically advanced stage prostate cancer. CONCLUSIONS: In this cohort of men with histologically diagnosed prostate cancer, low serum FT was associated with higher PSA, higher grade, and locally advanced or metastatic prostate cancer.