Chemokine Receptor-4 Targeted PET/CT Imaging with 68Ga-Pentixafor in Head and Neck Cancer-A Comparison with 18F-FDG and CXCR4 Immunohistochemistry.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is common, and its incidence is increasing, particularly in HIV-infected individuals who present with more aggressive disease. Despite aggressive treatment, the prognosis remains poor because of resistance to chemoradiation therapy. So far, studies report very low [68Ga]Ga-Pentixafor avidity in HNSCC. This study investigated the diagnostic performance of CXCR4-directed imaging of carcinoma of the oral cavity, oropharynx, and nasopharynx with positron emission tomography/computed tomography (PET/CT) using the radiolabelled chemokine ligand [68Ga]Ga-Pentixafor and explored its ability to quantify CXCR4 expression in vivo. MATERIALS AND METHODS: In this prospective cross-sectional study, twenty-three (23) patients aged 52.9 ± 10.4 (19.6), 17 males and 6 females with primarily diagnosed (n = 17) or pre-treated (n = 6) SCC of the oral cavity (OCSCC, n = 11), oropharynx (OPSCC, n = 9), nasopharynx (NPSCC, n = 2) and unknown primary (n = 1) underwent imaging with [68Ga]Ga-Pentixafor-PET/CT. In 16/23 patients 2-[18F]fluoro-2-deoxy-D-glucose ([18F]F-FDG) served as a standard reference. All lesions were visually rated using a 5-point Likert scale. For both tracers, maximum standardized uptake values (SUVmax) and the total lesion uptake (TLU) were recorded and compared using the Wilcox-signed rank test. In addition, the tumor-to-background ratios were derived using the liver (TLR), spleen (TSR), and posterior cervical muscles (TMR) as background. The relationships between the SUVs of the two tracers were assessed using the Spearman correlation. CXCR4 immunohistochemistry (IHC) staining was correlated with 68Ga-Pentixafor-PET/CT in 21/23 patients. RESULTS: Ninety-one percent (21/23) of tumors were visually detected on [68Ga]Ga-Pentixafor; however, [68Ga]Ga-Pentixafor was less intense compared with [18F]F-FDG-PET. Quantitative analysis showed higher [18F]F-FDG SUVmax in comparison with [68Ga]Ga-Pentixafor (16 ± 6.7 vs. 5.8 ± 2.6 g/mL, p = 0.011) and SUVmean (9.3 ± 4.1 vs. 3± 1.6 g/mL, p < 0.001) and TBR 4.9 ± 2.3 vs. 2.36 ± 1.4 p = 0.014. Nasopharyngeal cancer demonstrated more intense tracer accumulation than oropharyngeal and oral cavity malignancies. CXCR4 IHC staining was positive in 15/21 patients, and there was a statistically significant correlation between IHC staining and [68Ga]Ga-Pentixafor SUVmean r = 0.5 p = 0.027, and performance status r = 0.83 p = 0.0104. CONCLUSIONS: In conclusion, although [68Ga]Ga-Pentixafor cannot replace [18F]F-FDG as a diagnostic tool because of its lower avidity, the correlation between CXCR4 targeted 68Ga-Pentixafor PET imaging and CXCR4 IHC staining indicates the potential of 68Ga-Pentixafor as an effective tool for selecting patients who may benefit from therapies targeting CXCR4. In addition, [68Ga]Ga-Pentixafor has no physiological brown fat uptake, which often obscures cervical lesions on [18F]F-FDG PET/CT imaging.

The impact, perceptions and needs of parents of children with epidermolysis bullosa.

BACKGROUND:  Epidermolysis bullosa (EB) is a rare, incurable genodermatosis that presents with blistering and skin fragility. Complications can be localised or generalised, limited to the skin or have systemic effects resulting in death. Caring for a child with this painful condition can have a profound effect on the quality of life of parents and the family. There is currently no published research on the lived experience of parents caring for a child with EB in a resource-limited environment in Africa. METHOD:  This qualitative research used interpretative phenomenological analysis with the aim of understanding the lived experiences of parents caring for children with EB. Semi-structured interviews were conducted with 13 participants between May 2022 and October 2023. Guba's framework of trustworthiness was used to ensure rigour. RESULTS:  Seven experiential themes with associated sub-themes were identified. The themes were (1) grappling with understanding EB, (2) the psychological experience, (3) living with the responsibility, (4) barriers to feeling supported, (5) changing relational dynamics, (6) experience of healthcare professionals and (7) parental needs. CONCLUSION:  Parents caring for children with EB face emotional, physical, psychosocial and financial challenges. Addressing parents' needs and concerns will go a long way in decreasing this burden. A biopsychosocial approach with an awareness of cultural context is essential for family-centred holistic EB care.Contribution: This is the first study in Africa that focussed on the lived experiences of parents caring for a child with EB.

The landscape of paediatric hydrocephalus in the Province of KwaZulu-Natal. A comparative analysis of the referral pattern, aetiology and management outcomes over four distinct five-year periods.

BACKGROUND: Paediatric hydrocephalus causes significant health burden globally, particularly in low and middle-income countries. There's a dearth of data from specific regions such as KwaZulu-Natal, South Africa. This study aimed to investigate the landscape of paediatric hydrocephalus, comparing four distinct five-year periods. METHODS: Data were collected retrospectively (2003 to 2007, 2008 to 2012, and 2013 to 2017) and prospectively (2018 to 2022). Children (≤18 years) treated for hydrocephalus were included. Data on demographics, referral patterns, aetiology, treatment modalities, and outcomes were collected and analyzed. RESULTS: A total of 3325 children were treated. The peak period was 2008 to 2012 (35.3%). Majority (51.4%) were from rural areas (p=0.013) and 47.9% were referred from regional hospitals, p=<0.001. Males (56.4%) and infants (60.2%) were predominant groups (p<0.001). Post-infectious aetiology (32.7%) was predominant (p<0.001), particularly tuberculous meningitis (54.1%). Ventriculoperitoneal shunts (VPSs) were the mainstay treatment (84.2%), with notable complication rates (20.4%), including infections (9.6%). HIV co-infection was diagnosed in 2.5% of cases. Weekend procedures were associated with VPS complications (HR1.3, CI:1.03-1.66, p=0.03). The mortality rate was 7.9%, and age ≥1 year (HR, 2.43 CI: 1.87-3.17, p<0.001), tertiary hospital referral (HR 1.48, CI: 1.06-2.04, p=0.019), VPS infection (HR, 3.63 CI: 2.66-4.95, p<0.001), acute abdomen (HR 2.17, CI: 1.11-4.25, p=0.024) and pneumonia (HR 7.32, OR 4.84 -11.06, p<0.001) were associated with mortality. CONCLUSION: This study provides comprehensive insights into pediatric hydrocephalus in KZN. Monitoring temporal trends and predictors of outcomes will aid guide future interventions aimed at mitigating the burden of pediatric hydrocephalus in the region.

Ten years of ear, nose and throat (ENT) services in Southern Africa: a scoping review.

BACKGROUND: While ear, nose, and throat (ENT) diseases are a substantial threat to global health, comprehensive reviews of ENT services in Southern Africa remain scarce. OBJECTIVE: This scoping review provides a decade-long overview of ENT services in Southern Africa and identifies gaps in healthcare provision. From the current literature, we hope to provide evidence-based recommendations to mitigate the challenges faced by the resource-limited ENT service. DATA SOURCES: PubMed, Web of Science, EBSCOhost, Cochrane Library, Cochrane Library, and Scopus. REVIEW METHODS: On several databases, we conducted a comprehensive literature search on both quantitative and qualitative studies on ENT services in Southern Africa, published between 1 January 2014 and 27 February 2024. The extracted data from the analyzed studies was summarized into themes. RESULTS: Four themes in the fourteen studies included in the final analysis described the existing ENT services in Southern Africa: 1. Workforce scarcity and knowledge inadequacies, 2. Deficiencies in ENT infrastructure, equipment, and medication, 3. Inadequate ENT disease screening, management, and rehabilitation and 4. A lack of telehealth technology. CONCLUSION: The Southern African ENT health service faces many disease screening, treatment, and rehabilitation challenges, including critical shortages of workforce, equipment, and medication. These challenges, impeding patient access to ENT healthcare, could be effectively addressed by implementing deliberate policies to train a larger workforce, increase ENT funding for equipment and medication, promote telehealth, and reduce the patient cost of care.

Main findings: Ear, nose and throat (ENT) healthcare in Southern Africa faces critical shortages of workforce, equipment, and medication for disease screening, treatment and rehabilitation.Added knowledge: In this review, we identify challenges in the resource-limited Southern African ENT healthcare provision and provide evidence-based recommendations to mitigate these challenges.Global health impact for policy and action: Improving ENT service delivery in the resource-limited world requires deliberate policies that improve health worker training, expand financing and resource availability, incorporate new technology, and lower patient costs of care.

Back to the Basics of SARS-CoV-2 Biochemistry: Microvascular Occlusive Glycan Bindings Govern Its Morbidities and Inform Therapeutic Responses.

Consistent with the biochemistry of coronaviruses as well established over decades, SARS-CoV-2 makes its initial attachment to host cells through the binding of its spike protein (SP) to sialylated glycans (containing the monosaccharide sialic acid) on the cell surface. The virus can then slide over and enter via ACE2. SARS-CoV-2 SP attaches particularly tightly to the trillions of red blood cells (RBCs), platelets and endothelial cells in the human body, each cell very densely coated with sialic acid surface molecules but having no ACE2 or minimal ACE2. These interlaced attachments trigger the blood cell aggregation, microvascular occlusion and vascular damage that underlie the hypoxia, blood clotting and related morbidities of severe COVID-19. Notably, the two human betacoronaviruses that express a sialic acid-cleaving enzyme are benign, while the other three-SARS, SARS-CoV-2 and MERS-are virulent. RBC aggregation experimentally induced in several animal species using an injected polysaccharide caused most of the same morbidities of severe COVID-19. This glycan biochemistry is key to disentangling controversies that have arisen over the efficacy of certain generic COVID-19 treatment agents and the safety of SP-based COVID-19 vaccines. More broadly, disregard for the active physiological role of RBCs yields unreliable or erroneous reporting of pharmacokinetic parameters as routinely obtained for most drugs and other bioactive agents using detection in plasma, with whole-blood levels being up to 30-fold higher. Appreciation of the active role of RBCs can elucidate the microvascular underpinnings of other health conditions, including cardiovascular disease, and therapeutic opportunities to address them.

Wheel Replacing Pyramid: Better Paradigm Representing Totality of Evidence-Based Medicine.

Background: Evidence-based medicine (EBM), as originally conceived, used all types of peer-reviewed evidence to guide medical practice and decision-making. During the SARS-CoV-2 Coronavirus disease (COVID-19) pandemic, the standard usage of EBM, modeled by the Evidence-Based Medicine Pyramid, undermined EBM by incorrectly using pyramid levels to assign relative quality. The resulting pyramid-based thinking is biased against reports both in levels beneath randomized control trials (RCTs) and those omitted from the pyramid entirely. Thus, much of the evidence was ignored. Our desire for a more encompassing and effective medical decision-making process to apply to repurposed drugs led us to develop an alternative to the EBM Pyramid for EBM. Herein, we propose the totality of evidence (T-EBM) wheel. Objectives: To create an easily understood graphic that models EBM by incorporating all peer-reviewed evidence that applies to both new and repurposed medicines, and to demonstrate its potential utility using ivermectin as a case study. Methods: The graphics were produced using Microsoft Office Visio Professional 2003 except for part of the T-EBM wheel sunburst chart, which was produced using Microsoft 365 Excel. For the case study, PubMed® was used by searching for peer-reviewed reports containing "ivermectin" and either "covid" or "sars" in the title. Reports were filtered for those using ivermectin-based protocols in the treatment of COVID-19. The resulting 265 reports were evaluated for their study design types and treatment outcomes. The three-ringed graphical T-EBM wheel was composed of two inner rings showing all types of reports and an outer ring showing outcomes for each type. Findings-Conclusions: The T-EBM wheel avoids the biases of the EBM Pyramid and includes all types of reports in the pyramid along with reports such as population and mechanistic studies. In both early and late stages of medical emergencies, pyramid-based thinking may overlook indications of efficacy in regions of the T-EBM wheel beyond RCTs. This is especially true when searching for ways to prevent and treat a novel disease with repurposed therapeutics before RCTs, safety assessments, and mechanisms of action of novel therapeutics are established. As such, T-EBM Wheels should replace the EBM Pyramids in medical decision-making and education. T-EBM Wheels can be expanded upon by implementing multiple outer rings, one for each different kind of outcome (efficacy, safety, etc.). A T-EBM Wheel can be created for any proprietary or generic medicine. The ivermectin (IVM) T-EBM Wheel displays the efficacy of IVM-based treatments of COVID-19 in a color-coded graphic, visualizing each type of evidence and the proportions of each of their outcomes (positive, inconclusive, negative).

Diagnostic Differentiation between Pancreatitis and Pancreatic Cancer: A Scoping Review.

Pancreatitis, encompassing acute and chronic forms, and pancreatic cancer pose significant challenges to the exocrine tissue of the pancreas. Recurrence rates and complications following acute pancreatitis episodes can lead to long-term risks, including diabetes mellitus. Chronic pancreatitis can develop in approximately 15% of cases, regardless of the initial episode's severity. Alcohol-induced pancreatitis, idiopathic causes, cigarette smoking, and hereditary pancreatitis contribute to the progression to chronic pancreatitis. Chronic pancreatitis is associated with an increased risk of pancreatic cancer, with older age at onset and smoking identified as risk factors. This scoping review aims to synthesise recent publications (2017-2022) on the diagnostic differentiation between pancreatitis and pancreatic cancer while identifying knowledge gaps in the field. The review focuses on biomarkers and imaging techniques in individuals with pancreatitis and pancreatic cancer. Promising biomarkers such as faecal elastase-1 and specific chemokines offer non-invasive ways to assess pancreatic insufficiency and detect early biomarkers for chronic pancreatitis. Imaging techniques, including computed tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasound (EUS), and positron emission tomography (PET), aid in differentiating between chronic pancreatitis and pancreatic cancer. However, accurately distinguishing between the two conditions remains a challenge, particularly when a mass is present in the head of the pancreas. Several knowledge gaps persist despite advancements in understanding the association between pancreatitis and pancreatic cancer, including the correlation between histopathological grading systems, non-invasive imaging techniques, and biomarkers in chronic pancreatitis to determine the risk of progression to pancreatic cancer, as well as differentiating between the two conditions. Further research is necessary to enhance our understanding of these aspects, which can ultimately improve the diagnosis and management of pancreatitis and pancreatic cancer.

Factors associated with in-hospital mortality in HIV-infected children treated for tuberculous meningitis hydrocephalus.

PURPOSE: The study aimed to investigate factors associated with in-hospital mortality in children diagnosed with tuberculous meningitis (TBM) hydrocephalus and HIV co-infection undergoing cerebrospinal fluid diversion procedures and their complications. METHODS: Data were collected retrospectively and prospectively between 2007 and 2022. Data collected included demographics, clinical characteristics, antiretroviral therapy (ART) status, biochemistry results, CD4 count, radiology findings, CSF diversion procedures (and complications), length of hospital stay (LOHS), and in-hospital mortality. RESULTS: Thirty-one children were included, with a mean age of 6.7 ± 5.3 years and 67.7% males. Median admission Glasgow Coma Scale (GCS) was 11 (IQR 9-15). Hypertonia (64.5%) and seizures (51.6%) were frequently observed clinical characteristics. Sixty-one percent of children were on ART. Cerebral infarcts and extra-meningeal TB were diagnosed in 64.5% and 19.3% of cases, respectively. The median CD4 count was 151 (IQR 70-732) cells/µL. Surgical procedures included ventriculoperitoneal shunt (VPS) in 26 cases and endoscopic third ventriculostomy (ETV) in five children. VPS complication rate was 27%. No complications were reported for ETV. Median LOHS was 7 days (IQR 4-21). Eleven children (35.5%) died during admission. Factors associated with mortality included GCS (p = 0.032), infarcts (p = 0.004), extra-meningeal TB (p = 0.003), VPS infection (p = 0.018), low CD4 count (p = 0.009), and hyponatremia (p = 0.002). No statistically significant factors were associated with VPS complications. CONCLUSION: TBM hydrocephalus in HIV-infected children carries a high mortality. Clinicians in high-prevalence settings should have a high suspicion index and institute early treatment.

'It breaks my heart': Healthcare practitioners' caring for families with epidermolysis bullosa.

Background: Epidermolysis bullosa (EB) is a painful genodermatosis presenting with skin fragility and blisters. There is no cure; the prognosis is guarded and depends on the subtype of the disease. Managing these patients can be emotionally challenging for healthcare practitioners. Aim: To determine the perceptions, impact, and needs of healthcare practitioners (HCP) caring for patients and their families with EB. Setting: Nelson Mandela School of Medicine, Durban and Grey's Hospital, Pietermaritzburg, KwaZulu-Natal. Methods: The study was guided by interpretative phenomenological analysis. Individual in-depth interviews were conducted with 10 healthcare practitioners. Guba's trustworthiness framework was used to ensure rigour. Results: Six global themes were identified, each related primarily to the perceptions, impact, and needs of healthcare practitioners. The experiences and perceptions of healthcare practitioners were that caring for patients with an incurable disease such as EB could negatively impact healthcare practitioners. There were divergent views among the disciplines of HCPs regarding the extent of care in a resource-limited environment. This resulted in negative emotions, ethical concerns, and a need for continued medical education and the application of coping strategies. Healthcare practitioners observed that patients and their families were vulnerable, requiring comprehensive biopsychosocial care. Conclusion: Healthcare practitioners should be aware of their emotional challenges, seek support where necessary, and use effective coping strategies and self-care. Contribution: The concerns and needs of healthcare practitioners are highlighted and interventional strategies to assist healthcare practitioners are suggested which will ultimately improve patient care.

Ten-year predictors of major adverse cardiovascular events in patients without angina.

BACKGROUND: Longstanding cardiovascular risk factors cause major adverse cardiovascular events (MACE). Major adverse cardiovascular events prediction may improve outcomes. The aim was to evaluate the ten-year predictors of MACE in patients without angina. METHODS: Patients referred to Inkosi Albert Luthuli Hospital, Durban, South Africa, without typical angina from 2002 to 2008 were collected and followed up for MACE from 2009 to 2019. Survival time was calculated in months. Independent variables were tested with Cox proportional hazard models to predict MACE morbidity and MACE mortality. RESULTS: There were 525 patients; 401 (76.0%) were Indian, 167 (31.8%) had diabetes at baseline. At 10-year follow up 157/525 (29.9%) experienced MACE morbidity, of whom, 82/525 (15.6%) had MACE mortality. There were 368/525 (70.1%) patients censored, of whom 195/525 (37.1%) were lost to follow up. For MACE morbidity, mean and longest observation times were 102.2 and 201 months, respectively. Predictors for MACE morbidity were age (hazard ratio [HR] = 1.025), diabetes (HR = 1.436), Duke Risk category (HR = 1.562) and Ischaemic burden category (HR = 1.531). For MACE mortality, mean and longest observation times were 107.9 and 204 months, respectively. Predictors for MACE mortality were age (HR = 1.044), Duke Risk category (HR = 1.983), echocardiography risk category (HR = 2.537) and Ischaemic burden category (HR = 1.780). CONCLUSION: Among patients without typical angina, early ischaemia on noninvasive tests indicated microvascular disease and hyperglycaemia, predicting long-term MACE morbidity and MACE mortality.Contribution: Diabetes was a predictor for MACE morbidity but not for MACE mortality; patients lost to follow-up were possibly diabetic patients with MACE mortality at district hospitals. Early screening for ischaemia and hyperglycaemia control may improve outcomes.

Cardiac scoring systems, coronary artery disease and major adverse cardiovascular events: A scoping review.

BACKGROUND: In 2019, the World Health Organization (WHO) declared coronary artery disease (CAD) as the leading cause of death globally for the last 20 years. Early screening and detection (primary prevention) and intervention (secondary prevention) are necessary to curb CAD and major adverse cardiovascular event (MACE) prevalence. A scoping review to assess the current literature on using cardiac scoring systems to predict CAD and MACE was performed. METHODS: The research question 'What is the literature on using cardiac scoring systems to predict CAD and MACE?' was addressed. The updated Arksey and O'Malley and the Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews methodologies were used. The search terms 'coronary artery disease' and 'cardiac scoring systems' and 'major adverse cardiovascular events' were used in the Boolean search on PubMed, ScienceDirect, MedLine and Cochrane Library. RESULTS: The final list consisted of 19 published English results after the year 2000. There were six results without participants (four clinical guidelines, one review article and one ongoing clinical trial). Scoring systems were cardiovascular risk estimation systems focusing on the primary prevention of CAD; MACE was discussed but not scored. There were 13 robust results published from completed multinational clinical trials with participants. These results focused on a scoring system for the secondary prevention of CAD and MACE. CONCLUSION: Scoring systems remain an objective method for primary and secondary prevention of CAD and MACE.Contribution: Scoring systems may be helpful with clinical uncertainty or to standardise patient results for comparison in research.

A qualitative study on traditional healers' perceptions and management of epidermolysis bullosa.

Background: Epidermolysis bullosa (EB) is a rare, incurable genodermatosis causing blisters that can result in multisystemic complications and death. Limited data exists on EB in South Africa. Research indicates that the majority of African patients consult traditional health practitioners (THPs) before seeking allopathic healthcare. Aim: This study aims to understand THPs belief systems, experiences, perceptions and management of EB patients and their families in the social and cultural context to improve the healthcare of EB patients. Setting: The study setting is Nelson Mandela School of Medicine, Durban, and Grey's hospital, Pietermaritzburg, KwaZulu-Natal. Methods: Qualitative in-depth interviews were conducted with 10 THPs. A non-probability, purposive sampling method was used. A two-site qualitative study was guided by interpretative phenomenological analysis. Guba's trustworthiness framework was used to ensure rigour. Results: Three male and seven female THPs were interviewed, including sangoma, inyanga and umthandazi. The integration presented five global themes: (1) THP practices, (2) perceptions of THP, (3) experiences of THP with patients with EB, (4) diagnosis and management plans of THP and (5) vision and role of THPs. There were multiple divergent perspectives among the THPs with the shared African worldview. Conclusion: Understanding THPs belief systems and therapeutic options is crucial for holistic patient management. Knowledge exchange can promote safe healthcare practices and facilitate collaboration between traditional and allopathic health practitioners. Contribution: This is the first study to explore THPs perceptions and practices regarding EB, a rare disease.

Genome-wide association study of esophageal squamous cell cancer identifies shared and distinct risk variants in African and Chinese populations.

Esophageal squamous cell carcinoma (ESCC) has a high disease burden in sub-Saharan Africa and has a very poor prognosis. Genome-wide association studies (GWASs) of ESCC in predominantly East Asian populations indicate a substantial genetic contribution to its etiology, but no genome-wide studies have been done in populations of African ancestry. Here, we report a GWAS in 1,686 African individuals with ESCC and 3,217 population-matched control individuals to investigate its genetic etiology. We identified a genome-wide-significant risk locus on chromosome 9 upstream of FAM120A (rs12379660, p = 4.58 × 10-8, odds ratio = 1.28, 95% confidence interval = 1.22-1.34), as well as a potential African-specific risk locus on chromosome 2 (rs142741123, p = 5.49 × 10-8) within MYO1B. FAM120A is a component of oxidative stress-induced survival signals, and the associated variants at the FAM120A locus co-localized with highly significant cis-eQTLs in FAM120AOS in both esophageal mucosa and esophageal muscularis tissue. A trans-ethnic meta-analysis was then performed with the African ESCC study and a Chinese ESCC study in a combined total of 3,699 ESCC-affected individuals and 5,918 control individuals, which identified three genome-wide-significant loci on chromosome 9 at FAM120A (rs12379660, pmeta = 9.36 × 10-10), chromosome 10 at PLCE1 (rs7099485, pmeta = 1.48 × 10-8), and chromosome 22 at CHEK2 (rs1033667, pmeta = 1.47 × 10-9). This indicates the existence of both shared and distinct genetic risk loci for ESCC in African and Asian populations. Our GWAS of ESCC conducted in a population of African ancestry indicates a substantial genetic contribution to ESCC risk in Africa.

The review of genetic screening services and common BRCA1/2 variants among South African breast cancer patients.

The South African genetic screening services for breast cancer comprise targeted and comprehensive tests that screen for the presence of genetic alterations. Clinically, these variants determine the risk of disease development as well as treatment approaches best suited for carriers. The current targeted tests screen for seven pathogenic sequence variants, which are mainly common among Whites, a population that constitutes 9.1% of South Africa. However, these tests are offered to all patients despite consistent negative results observed among Blacks, Indians, and Mixed ancestry (known as Coloreds in South Africa). Consequently, Blacks, White, and Colored patients who potentially carry other variants receive unbefitting treatment, resulting in poor clinical response, recurrence, and high mortality. This review aimed to identify the presence and incidence of pathogenic variants in BRCA1/2 previously reported in all South African populations. We selected literature using a scoping review approach, from which we included eight articles and two reports. Overall, we identified 59 BRCA1 and 60 BRCA2 pathogenic sequence variants from a cohort of 5709 patients and unknown patients from 90 families. The most reported variant was BRCA2 c.7943delG, which was common in White and Colored patients. None of the seven common variants was reported in either Blacks or Indians, which demonstrates the urgency to tailor genetic tests which are optimal for all South African patients and present a range of variants which could serve as diagnostic targets for Black, Indian, and Colored patients.

When Characteristics of Clinical Trials Require Per-Protocol as Well as Intention-to-Treat Outcomes to Draw Reliable Conclusions: Three Examples.

Under exceptional circumstances, including high rates of protocol non-compliance, per-protocol (PP) analysis can better indicate the real-world benefits of a medical intervention than intention-to-treat (ITT) analysis. Exemplifying this, the first randomized clinical trial (RCT) considered found that colonoscopy screenings were marginally beneficial, based upon ITT analysis, with only 42% of the intervention group actually undergoing the procedure. However, the study authors themselves concluded that the medical efficacy of that screening was a 50% reduction in colorectal cancer deaths among that 42% PP group. The second RCT found a ten-fold reduction in mortality for a COVID-19 treatment drug vs. placebo by PP analysis, but only a minor benefit by ITT analysis. The third RCT, conducted as an arm of the same platform trial as the second RCT, tested another COVID-19 treatment drug and reported no significant benefit by ITT analysis. Inconsistencies and irregularities in the reporting of protocol compliance for this study required consideration of PP outcomes for deaths and hospitalizations, yet the study coauthors refused to disclose them, instead directing inquiring scientists to a data repository which never held the study's data. These three RCTs illustrate conditions under which PP outcomes may differ significantly from ITT outcomes and the need for data transparency when these reported or indicated discrepancies arise.

Update on PET Radiopharmaceuticals for Imaging Hepatocellular Carcinoma.

Numerous positron emission tomography (PET) targets for detection and staging of hepatocellular cancer have been developed in recent years. Hepatocellular carcinomas (HCCs) are clinically and pathologically heterogeneous tumours with a high tendency to be aggressive and unresponsive to chemotherapy. Early detection is essential, and the need for an adequate imaging biomarker, which can overcome some of the limitations of conventional radiological imaging, is persistent. Flourine-18 (18F) flourodeoxyglucose (FDG), the most widely used PET radiopharmaceutical, has proven disappointing as a possible staple in the evaluation of HCC. This disappointment had led to experimentation with carious radiotracers, such as the choline derivatives, acetate, and prostate-specific membrane antigen, which appear to complement and/or enhance the role of FDG. In this study, we look at the various PET radiopharmaceuticals that have been used for imaging HCC and the particular pathways that they target in HCC and liver cancers.

Novel IRF6 variant in orofacial cleft patients from Durban, South Africa.

BACKGROUND: To date, there are over 320 variants identified in the IRF6 gene that cause Van der Woude syndrome or popliteal pterygium syndrome. We sequenced this gene in a South African orofacial cleft cohort to identify the causal IRF6 variants in our population. METHOD: Saliva samples from 100 patients with syndromic and non-syndromic CL ± P were collected. Patients were recruited from the cleft clinics at two public, tertiary hospitals in Durban, South Africa (SA), namely Inkosi Albert Luthuli Central Hospital (IALCH) and KwaZulu-Natal Children's Hospital (KZNCH). We prospectively sequenced the exons of IRF6 in 100 orofacial cleft cases, and where possible, we also sequenced the parents of the individuals to determine the segregation pattern. RESULTS: Two variants were identified; one novel (p.Cys114Tyr) and one known (p.Arg84His) missense variant in IRF6 gene were identified. The patient with the p.Cys114Tyr variant was non-syndromic with no clinical VWS phenotype expected of individuals with IRF6 coding variants, and the patient with the p.Arg84His had phenotypic features of popliteal pterygium syndrome. The p.Arg84His variant segregated in the family, with the father also being affected. CONCLUSIONS: This study provides evidence that IRF6 variants are found in the South African population. Genetic counselling is essential for affected families, particularly in the absence of a known clinical phenotype since it helps with the plans for future pregnancies.

Ear, Nose and Throat (ENT) disease diagnostic error in low-resource health care: Observations from a hospital-based cross-sectional study.

Although the global burden of ear, nose and throat (ENT) diseases is high, data relating to ENT disease epidemiology and diagnostic error in resource-limited settings remain scarce. We conducted a retrospective cross-sectional review of ENT patients' clinical records at a resource-limited tertiary hospital. We determined the diagnostic accuracy and appropriateness of patient referrals for ENT specialist care using descriptive statistics. Cohens kappa coefficient (κ) was calculated to determine the diagnostic agreement between non-ENT clinicians and the ENT specialist, and logistic regression applied to establish the likelihood of patient misdiagnosis by non-ENT clinicians. Of the 1543 patients studied [age 0-87 years, mean age 25(21) years (mean(SD)], non-ENT clinicians misdiagnosed 67.4% and inappropriately referred 50.4%. Compared to those aged 0-5 years, patients aged 51-87 years were 1.77 (95%CI: 1.03-3.04) fold more likely to have a referral misdiagnosis for specialist care. Patients with ear (aOR: 1.63; 95% CI: 1.14-2.33) and those with sinonasal diseases (aOR: 1.80; 95% CI: 1.14-2.45) had greater likelihood of referral misdiagnosis than those with head and neck diseases. Agreement in diagnosis between the ENT specialist and non-ENT clinicians was poor (κ = 0.0001). More effective, accelerated training of clinicians may improve diagnostic accuracy in low-resource settings.

The impact of epidermolysis bullosa on the family and healthcare practitioners: a scoping review.

BACKGROUND: Epidermolysis bullosa (EB) is an inherited genodermatosis that results in mucocutaneous fragility. There is a lack of data on the impact of this disease on parents. There are no studies on the impact on siblings and few on healthcare professionals in dealing with this devastating disease. METHODS: A scoping review was performed using the Arksey and O'Malley and PRISMA-ScR framework. Twenty-seven articles were reviewed, and a data-charting sheet was formulated. RESULTS: Parents make great sacrifices and are resilient in caring for their sick children but are at risk of depression. Siblings play a vital role in caring for their siblings, but their needs may be overlooked because the main focus is on the sibling with EB. Healthcare professionals may suffer burnout and compassion fatigue in caring for patients and their families with EB. CONCLUSION: Comprehensive care of the family and the awareness of the challenges experienced by healthcare professionals is essential to the holistic care of a patient with EB.

Interrogating the lack of diversity of thought in the pandemic response that led to mistakes - holistic evidence-based approach to deal with future pandemics.

The COVID-19 pandemic, triggered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapidly became a worldwide emergency. How it was managed garnered both commendation and vehement censure. This crisis profoundly affected healthcare, the economy, education, and public confidence in scientific endeavors. Our primary aim was to scrutinize the shortcomings in the pandemic management and to articulate a more effective strategy for handling prospective pandemics. We delved into the errors encountered in the COVID-19 response and posited a holistic, evidence-grounded approach for future pandemic mitigation.