Approach to the diagnosis and management of snakebite envenomation in South Africa in humans: Special patient groups and surgical aspects.

This article explores the management of snakebite to vulnerable patient groups, namely children and pregnant women as well as providing detail on the current best practice when caring for venom ophthalmia and surgical wounds resulting from snakebite. Finally, the optimal free-to-use medical record for accurate documentation of snakebite incidents is provided for use by South African practitioners.

Approach to the diagnosis and management of snakebite envenomation in South Africa in humans.

Snake bite management is largely driven by expert opinion and consensus, however there are a few large retrospective studies and RCT's that have improved the quality of medical guidance currently available. South African snakes are different in the venomous potential and it behooves the hospital provider and the average medical practitioner to know the current best practice concepts concerning assessment, treatment and antivenom use. The recent SASS meeting in July 2022 provided an update and national consensus from which this Hospital Care document is derived.

Point-of-care ultrasound assessment of a swollen limb following snakebite envenomation - an adjunct to avoid fasciotomy.

SUMMARY: Acute limb compartment syndrome can occur with cytotoxic snake envenomation. Ultrasound (US) assessment of the affected limb has been suggested as an adjunct to the administration of snakebite polyvalent antivenom to ameliorate the systemic and local effects. US may also aid in the diagnosis of compartment syndrome and the need for fasciotomy to prevent limb loss. This report presents an adult male who had severe soft tissue swelling from a puff adder bite to the wrist and highlights the use of US in assessing and monitoring the degree of swelling in subcutaneous and fascial compartments of the arm. This US monitoring in conjunction with frequent physical examination avoided the need for a fasciotomy and its attendant morbidity, resulting in complete resolution of the swelling and full recovery of limb function.

Recognition of infants at high risk for vertical HIV transmission at delivery in rural Western Cape Province, South Africa.

Background: Despite South Africa's substantial reduction in vertical HIV transmission (VHT), national paediatric HIV elimination is not yet attained. National and Western Cape Province (WC) HIV guidelines recommend enhanced postnatal prophylaxis for infants at high risk for VHT, identified in the WC 2015/2016 guidelines by any single high-risk criterion (maternal antiretroviral therapy (ART) <12 weeks, absent/ unsuppressed maternal HIV viral load (HIV-VL) <12 weeks before/including delivery, spontaneous preterm labour, prolonged rupture of membranes, chorioamnionitis). Accuracy of high-risk infant identification is unknown. Objectives: Primarily, to determine the proportion of infants at high risk for VHT, the accuracy of labour-ward risk classification, the criteria determining high-risk statuses and the criteria missed among unrecognised high-risk infants; secondarily, to determine maternal factors associated with high-risk infants. Methods: Infants born to women living with HIV at a rural regional hospital (May 2016 - April 2017) were retrospectively evaluated using data from the labour ward VHT register, standardised maternity case records, National Health Laboratory Service database and WC Provincial Health Data Centre. The study-derived risk status for each infant was determined using documented presence/absence of risk criteria and compared with labour ward assigned risk to determine accuracy. Proportions of high-risk and unrecognised high-risk infants with each high-risk criterion were determined. Maternal characteristics associated with having a high-risk infant were evaluated using multivariable logistic regression. Results: For liveborn infants, labour ward assigned risk classifications were 40% (n=75/188) high risk, 50% (n=94/188) low risk and 10% (n=19/188) unclassified. Study-derived risk was high risk for 69% (n=129/188) and low risk for 31% (n=59/188), yielding a high-risk classification sensitivity of 51% (95% confidence interval (CI) 42 - 60) and specificity of 69% (95% CI 56 - 80). Absent/unsuppressed HIVVL <12 weeks before delivery accounted for 83% (n=119/143) of study-derived high-risk exposures and 81% (n=60/74) of missed high-risk exposures. Fewer mothers of high-risk infants had >4 antenatal visits (38% v. 81%, p<0.01) and first antenatal visit <20 weeks' gestation (57% v. 77%, p=0.01). Only the number of antenatal visits remained associated with having a high-risk infant after adjusting for gestation at first visit and timing of HIV diagnosis and ART initiation: each additional antenatal visit conferred a 39% (95% CI 25 - 50) reduction in the odds of having a high-risk infant. Conclusion: Labour ward risk classification failed to recognise half of high-risk infants. Infant high-risk status as well as non-detection thereof were driven by suboptimal maternal HIV-VL monitoring. Reinforcing visit frequency later in pregnancy may improve antenatal HIV-VL monitoring, and point-of-care HIV-VL monitoring at delivery could improve recognition of virally unsuppressed mothers and their high-risk infants.

Rationalising empirical antibiotics for bloodstream infections: A retrospective study at a South African district-level hospital.

BACKGROUND: Incorrect empirical antibiotic therapy is one of the factors that contribute to poor clinical outcomes and the development of antimicrobial resistance. Knowledge of the local infectious disease burden and antibiotic resistance patterns can assist with development of strategies, updating of guidelines and subsequent improvement in initial empirical therapy. OBJECTIVES: To determine whether the empirical antibiotic choice for treatment of septic episodes at a district-level hospital was appropriate according to national guidelines, and to describe the epidemiological features of the septic episode population being studied and depict their antibiotic susceptibility profile. METHODS: This was a retrospective, descriptive study of adult inpatients with bloodstream infections at Karl Bremer Hospital, Cape Town, South Africa. Laboratory and clinical data were obtained and analysed for the period 1 July 2017 - 30 June 2018. Septic episodes were subdivided into community-acquired bloodstream infection (CABSI) and hospital-acquired bloodstream infection (HABSI) study populations, and empirical antibiotics for both groups were assessed and compared with the adult Standard Treatment Guidelines and Essential Medicines List for South Africa, Hospital Level Care, 2015 edition (STG and EML). RESULTS: Our study sample consisted of 184 septic episodes, isolated from 176 patients. Nearly half of the septic episodes (49.5%) were hospital acquired. Overall guideline adherence in the CABSI population was 88%, compared with 58% in the HABSI population. The reasons for guideline non-adherence in the CABSI population were lack of source-appropriate empirical antibiotics (n=7) and septic episodes where empirical antibiotics were indicated but not prescribed (n=4), while in the HABSI group the main reason was that the patients were treated by community-acquired standards (n=30; 33.0%). The in-hospital mortality rate for a septic episode in this study was 38%. Considering the typical first-line antibiotics used, 77.3% of CABSIs were found to be susceptible to co-amoxiclav (n=75) and 59.8% to ceftriaxone (n=58). With the exclusion of methicillin-resistant Staphylococcus aureus and Acinetobacter baumannii isolates as confounders, HABSIs had a susceptibility of 86% to the piperacillin/tazobactam plus amikacin combination, 81% to ertapenem, 90% to imipenem and 93% to meropenem. CONCLUSIONS: This study demonstrates poor guideline adherence in HABSIs, emphasising the importance of distinguishing between CABSIs and HABSIs. The empirical antibiotics advised by the STG and EML were found to be appropriate in the majority of septic episodes. Future revision and improvement of prescribing practices can assist in rationalising empirical antibiotic decisions.

Decreased severity of disease during the first global omicron variant covid-19 outbreak in a large hospital in tshwane, south africa.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) first reported in Wuhan, China in December 2019 is a global pandemic that is threatening the health and wellbeing of people worldwide. To date there have been more than 274 million reported cases and 5.3 million deaths. The Omicron variant first documented in the City of Tshwane, Gauteng Province, South Africa on 9 November 2021 led to exponential increases in cases and a sharp rise in hospital admissions. The clinical profile of patients admitted at a large hospital in Tshwane is compared with previous waves. METHODS: 466 hospital COVID-19 admissions since 14 November 2021 were compared to 3962 admissions since 4 May 2020, prior to the Omicron outbreak. Ninety-eight patient records at peak bed occupancy during the outbreak were reviewed for primary indication for admission, clinical severity, oxygen supplementation level, vaccination and prior COVID-19 infection. Provincial and city-wide daily cases and reported deaths, hospital admissions and excess deaths data were sourced from the National Institute for Communicable Diseases, the National Department of Health and the South African Medical Research Council. RESULTS: For the Omicron and previous waves, deaths and ICU admissions were 4.5% vs 21.3% (p<0.00001), and 1% vs 4.3% (p<0.00001) respectively; length of stay was 4.0 days vs 8.8 days; and mean age was 39 years vs 49,8 years. Admissions in the Omicron wave peaked and declined rapidly with peak bed occupancy at 51% of the highest previous peak during the Delta wave. Sixty two (63%) patients in COVID-19 wards had incidental COVID-19 following a positive SARS-CoV-2 PCR test . Only one third (36) had COVID-19 pneumonia, of which 72% had mild to moderate disease. The remaining 28% required high care or ICU admission. Fewer than half (45%) of patients in COVID-19 wards required oxygen supplementation compared to 99.5% in the first wave. The death rate in the face of an exponential increase in cases during the Omicron wave at the city and provincial levels shows a decoupling of cases and deaths compared to previous waves, corroborating the clinical findings of decreased severity of disease seen in patients admitted to the Steve Biko Academic Hospital. CONCLUSION: There was decreased severity of COVID-19 disease in the Omicron-driven fourth wave in the City of Tshwane, its first global epicentre.

Cancer and Covid-19: Collectively catastrophic.

The Covid-19 pandemic has spread rapidly across the globe, resulting in more than 3 million deaths worldwide. The symptoms of Covid-19 are usually mild and non-specific, however in some cases patients may develop acute respiratory distress syndrome (ARDS) and systemic inflammation. Individuals with inflammatory or immunocompromising illnesses, such as cancer, are more susceptible to develop ARDS and have higher rates of mortality. This is mediated through an initial hyperstimulated immune response which results in elevated levels of pro-inflammatory cytokines and a subsequent cytokine storm. This potentiates positive feedback loops which are unable to be balanced by anti-inflammatory mediators. Therefore, elevated levels of IL-1ß, as a result of NLRP3 inflammasome activation, as well as IL-6 and TNF-α amongst many others, contribute to the progression of various cancer types. Furthermore, Covid-19 progression is associated with the depletion of CD8+ and CD4+ T cells, B cell and natural killer cell numbers. Collectively, a Covid-19-dependent pro-inflammatory profile and immune suppression promotes the optimal microenvironment for tumourigenesis, initiation and immune evasion of malignant cells, tumour progression and metastasis as well as cancer recurrence. There are, however, therapeutic windows of opportunity that may combat both Covid-19 and cancer to improve patient outcomes.

Recognition of infants at high risk for vertical HIV transmission at delivery in rural Western Cape Province, South Africa

Despite South Africa's substantial reduction in vertical HIV transmission (VHT), national paediatric HIV elimination is not yet attained. National and Western Cape Province (WC) HIV guidelines recommend enhanced postnatal prophylaxis for infants at high risk for VHT, identified in the WC 2015/2016 guidelines by any single high-risk criterion (maternal antiretroviral therapy (ART) <12 weeks, absent/ unsuppressed maternal HIV viral load (HIV-VL) <12 weeks before/including delivery, spontaneous preterm labour, prolonged rupture of membranes, chorioamnionitis). Accuracy of high-risk infant identification is unknown. Objectives. Primarily, to determine the proportion of infants at high risk for VHT, the accuracy of labour-ward risk classification, the criteria determining high-risk statuses and the criteria missed among unrecognised high-risk infants; secondarily, to determine maternal factors associated with high-risk infants. Methods. Infants born to women living with HIV at a rural regional hospital (May 2016 - April 2017) were retrospectively evaluated using data from the labour ward VHT register, standardised maternity case records, National Health Laboratory Service database and WC Provincial Health Data Centre. The study-derived risk status for each infant was determined using documented presence/absence of risk criteria and compared with labour ward assigned risk to determine accuracy. Proportions of high-risk and unrecognised high-risk infants with each high-risk criterion were determined. Maternal characteristics associated with having a high-risk infant were evaluated using multivariable logistic regression. Results. For liveborn infants, labour ward assigned risk classifications were 40% (n=75/188) high risk, 50% (n=94/188) low risk and 10% (n=19/188) unclassified. Study-derived risk was high risk for 69% (n=129/188) and low risk for 31% (n=59/188), yielding a high-risk classification sensitivity of 51% (95% confidence interval (CI) 42 - 60) and specificity of 69% (95% CI 56 - 80). Absent/unsuppressed HIVVL <12 weeks before delivery accounted for 83% (n=119/143) of study-derived high-risk exposures and 81% (n=60/74) of missed high-risk exposures. Fewer mothers of high-risk infants had >4 antenatal visits (38% v. 81%, p<0.01) and first antenatal visit <20 weeks' gestation (57% v. 77%, p=0.01). Only the number of antenatal visits remained associated with having a high-risk infant after adjusting for gestation at first visit and timing of HIV diagnosis and ART initiation: each additional antenatal visit conferred a 39% (95% CI 25 - 50) reduction in the odds of having a high-risk infant. Conclusion. Labour ward risk classification failed to recognise half of high-risk infants. Infant high-risk status as well as non-detection thereof were driven by suboptimal maternal HIV-VL monitoring. Reinforcing visit frequency later in pregnancy may improve antenatal HIV-VL monitoring, and point-of-care HIV-VL monitoring at delivery could improve recognition of virally unsuppressed mothers and their high-risk infants

Molecular regulation of autophagy in a pro-inflammatory tumour microenvironment: New insight into the role of serum amyloid A.

Chronic inflammation, systemic or local, plays a vital role in tumour progression and metastasis. Dysregulation of key physiological processes such as autophagy elicit unfavourable immune responses to induce chronic inflammation. Cytokines, growth factors and acute phase proteins present in the tumour microenvironment regulate inflammatory responses and alter crosstalk between various signalling pathways involved in the progression of cancer. Serum amyloid A (SAA) is a key acute phase protein secreted by the liver during the acute phase response (APR) following infection or injury. However, cancer and cancer-associated cells produce SAA, which when present in high levels in the tumour microenvironment contributes to cancer initiation, progression and metastasis. SAA can activate several signalling pathways such as the PI3K and MAPK pathways, which are also known modulators of the intracellular degradation process, autophagy. Autophagy can be regarded as having a double edged sword effect in cancer. Its dysregulation can induce malignant transformation through metabolic stress which manifests as oxidative stress, endoplasmic reticulum (ER) stress and DNA damage. On the other hand, autophagy can promote cancer survival during metabolic stress, hypoxia and senescence. Autophagy has been utilised to promote the efficiency of chemotherapeutic agents and can either be inhibited or induced to improve treatment outcomes. This review aims to address the known mechanisms that regulate autophagy as well as illustrating the role of SAA in modulating these pathways and its clinical implications for cancer therapy.

An electronic survey of preferred podcast format and content requirements among trainee emergency medicine specialists in four Southern African universities.

INTRODUCTION: Global usage of educational Emergency Medicine (EM) podcasts is popular and ever-increasing. This study aims to explore the desired content, format and delivery characteristics of a potential educational, context-specific Southern African EM podcast, by investigating current podcast usages, trends and preferences among Southern African EM registrars of varying seniority. METHODS: We developed an electronic survey - using a combination of existing literature, context-specific specialist-training guidance, and input from local experts - exploring preferred podcast characteristics among EM registrars from four Southern African universities. RESULTS: The study's response rate was 75%, with 24 of the 39 respondents being junior registrars. Ninety-four percent (94%) of respondents used EM podcasts as an educational medium: 64% predominantly using podcasts to supplement a personal EM study program. The primary mode of accessing podcasts was via personal mobile devices (84%). Additionally, respondents preferred a shorter podcast duration (5-15 min), favoured multimedia podcasts (56%) and showed an apparent aversion toward recorded faculty lectures (5%). Eighty-two percent (82%) of respondents preferred context-specific podcast content, with popular topics including toxicology (95%), cardiovascular emergencies (79%) and medico-legal matters (74%). Just-in-Time learning proved an unpopular learning strategy in our study population, despite its substantial educational value. CONCLUSION: Podcast-usage proved to be near-ubiquitous among the studied Southern African EM registrars. Quintessentially, future context-specific podcast design should cater for mobile device-use, shorter duration podcasts, more video content, context-specific topics, and content optimised for both Just-in-Time learning.

There are three species of Chrysaora (Scyphozoa: Discomedusae) in the Benguela upwelling ecosystem, not two.

Chrysaora (Pèron Lesueur 1810) is the most diverse genus within Discomedusae, and 15 valid species are currently recognised, with many others not formally described. Since Chrysaora fulgida (Reynaud 1830) was first recognised as occurring off the south west (SW) coast off South Africa, the species has been variously synonymised with Chrysaora hysoscella (Linnaeus 1767) and Chrysaora africana (Vanhöffen 1902). Using DNA evidence alongside multivariate tools to analyse quantitative morphometric and meristic data, as well as information from the cnidome, we unambiguously separate C. fulgida from C. hysoscella; we resurrect C. africana as a valid species and recognise a new species, Chrysaora agulhensis sp. nov. Full descriptions of C. fulgida, C. africana and C. agulhensis sp. nov. are provided. The species have different geographical patterns of distribution around the region, with restricted areas of overlap: C. agulhensis sp. nov. is found along the southern coast of South Africa and over the Agulhas Bank, C. fulgida extends from Cape Point in South Africa to southern Angola, and C. africana can be found from southern Namibia northwards to the Gulf of Guinea. The species can be readily separated in the field by a combination of tentacle/lappet number and shape, colour patterns and the form of the oral arms.

Meat quality, skin damage and reproductive performance of ostriches exposed to extensive human presence and interactions at an early age.

The effect human presence and interactions performed after hatch to 3 months of age has on ostrich meat quality, skin damage and reproductive performance at a later age was investigated in 416-day-old ostrich chicks. The chicks were allocated to one of the three treatments, which varied with regard to exposure to human presence and care for 3 months post-hatch: HP1-extensive human presence with physical contact (touch, stroking), gentle human voice and visual contact; HP2-extensive human presence with gentle human voice and visual contact without physical contact; S-standard control treatment, where human presence and visual contact were limited to routine management, feed and water supply only. Carcass attributes (carcass weight, dressing percentage and drumstick weight), meat quality traits (pH, colour and tenderness) and skin traits (skin size, skin grading and number of lesions) were evaluated on twenty-four 1-year-old South African Black (SAB) ostriches. Reproductive performance (egg production, average egg weight, number of clutches, clutch size, chick production, average chick weight, fertility and hatchability percentage) were recorded for the first three breeding seasons of 23 SAB pair-bred females from this study. No differences in carcass attributes, meat quality, skin traits and reproductive performance were found between treatments (P > 0.05). It was evident that exposure of day-old ostriches to extensive human presence and interaction as chicks did not influence carcass attributes, meat quality or skin traits at slaughter age, but more importantly, it did not compromise their reproductive performance.

Anti-inflammatory mechanisms of cannabinoids: an immunometabolic perspective.

A number of studies have implicated cannabinoids as potent anti-inflammatory mediators. However, the exact mechanism by which cannabinoids exert these effects remains to be fully explained. The recent resurgence in interest regarding the metabolic adaptations undergone by activated immune cells has highlighted the intricate connection between metabolism and an inflammatory phenotype. In this regard, evidence suggests that cannabinoids may alter cell metabolism by increasing AMPK activity. In turn, emerging evidence suggests that the activation of AMPK by cannabinoids may mediate an anti-inflammatory effect through a range of processes. First, AMPK may promote oxidative metabolism, which have been shown to play a central role in immune cell polarisation towards a tolerogenic phenotype. AMPK activation may also attenuate anabolic processes which in turn may antagonise immune cell function. Furthermore, AMPK activity promotes the induction of autophagy, which in turn may promote anti-inflammatory effects through various well-described processes. Taken together, these observations implicate cannabinoids to mediate part of their anti-inflammatory effects through alterations in immune cell metabolism and the induction of autophagy.

Fatty acids: Adiposity and breast cancer chemotherapy, a bad synergy?

Globally, breast cancer continues to be a major concern in women's health. Lifestyle related risk factors, specifically excess adipose tissue (adiposity) has reached epidemic proportions and has been identified as a major risk factor in the development of breast cancer. Dysfunctional adipose tissue has evoked research focusing on its association with metabolic-related conditions, breast cancer risk and progression. Adipose dysfunction in coordination with immune cells and inflammation, are responsible for accelerated cell growth and survival of cancer cells. Recently, evidence also implicates adiposity as a potential risk factor for chemotherapy resistance. Chemotherapeutic agents have been shown to negatively impact adipose tissue. Since adipose tissue is a major storage site for fatty acids, it is not unlikely that these negative effects may disrupt adipose tissue homeostasis. It is therefore argued that fatty acid composition may be altered due to the chemotherapeutic pharmacokinetics, which in turn could have severe health related outcomes. The underlying molecular mechanisms elucidating the effects of fatty acid composition in adiposity-linked drug resistance are still unclear and under explored. This review focuses on the potential role of adiposity in breast cancer and specifically emphasizes the role of fatty acids in cancer progression and treatment resistance.

The role of mTOR during cisplatin treatment in an in vitro and ex vivo model of cervical cancer.

Cisplatin is used as a cytotoxic agent for the management of cervical cancer. However, the severity of the side-effects limits the use of this drug, particularly at high doses. Resistance to cisplatin is often attributed to a disruption in the normal apoptotic response via aberrant activation of pathways such as the mTOR pathway. Here we assess the role of mTOR and its effect on cell death sensitization and autophagy in response to a low concentration of cisplatin in cervical cancer cells. Additionally we measured the expression profile of mTOR in normal, low- and high-grade squamous intraepithelial (LSIL and HSIL) lesions and cancerous tissue. An in vitro model of cervical cancer was established using HeLa and CaSki cells. mTOR protein expression as well as autophagy-related proteins were evaluated through Western blotting. Inhibition of mTOR was achieved with the use of rapamycin and RNA silencing. A low concentration of cisplatin administered as a single agent induces autophagy, but not apoptosis. Cisplatin cytotoxicity was greatly enhanced in cancer cells when mTOR had been inhibited prior to cisplatin treatment which was likely due to autophagy being increased above cisplatin-induced levels, thereby inducing apoptosis. Cervical tissue samples revealed an increase in mTOR protein expression in LSIL and carcinoma tissue which suggests a change in autophagy control. Our data suggest that utilising a lower dose of cisplatin combined with mTOR inhibition is a viable treatment option and addresses the challenge of cisplatin dose-dependent toxicity, however future studies are required to confirm this in a clinical setting.

AHNAK: the giant jack of all trades.

The nucleoprotein AHNAK is an unusual and somewhat mysterious scaffolding protein characterised by its large size of approximately 700 kDa. Several aspects of this protein remain uncertain, including its exact molecular function and regulation on both the gene and protein levels. Various studies have attempted to annotate AHNAK and, notably, protein interaction and expression analyses have contributed greatly to our current understanding of the protein. The implicated biological processes are, however, very diverse, ranging from a role in the formation of the blood-brain barrier, cell architecture and migration, to the regulation of cardiac calcium channels and muscle membrane repair. In addition, recent evidence suggests that AHNAK might be yet another accomplice in the development of tumour metastasis. This review will discuss the different functional roles of AHNAK, highlighting recent advancements that have added foundation to the proposed roles while identifying ties between them. Implications for related fields of research are noted and suggestions for future research that will assist in unravelling the function of AHNAK are offered.