The prevalence of human papillomavirus in ocular surface squamous neoplasia in HIV positive and negative patients in a South African population.

PURPOSE: To assess the prevalence and subtypes of Human Papillomavirus (HPV) in Ocular Surface Squamous Neoplasia (OSSN) in Human Immunodeficiency Virus (HIV) positive and negative patients in South Africa. BASIC PROCEDURES: This study was a single center retrospective cross-sectional study, conducted at Tygerberg Hospital, Western Cape, South Africa. We assessed 63 histopathologically confirmed OSSN formalin-fixed paraffin-embedded (FFPE) tissue blocks from 2015-2023. The presence of HPV was determined using the Hybrispot Direct Flow Chip Kit. Corresponding clinical data was retrieved from the National Health Laboratory Service (NHLS) central data warehouse. MAIN FINDINGS: Of the confirmed OSSN samples, 66.7% tested positive for HPV (95% confidence interval [CI] 54-77.3%). Of the 42 HPV positive samples, 38 (90.5%) had one or more known genotypes detected and 4 had unknown genotypes. The most prevalent subtypes were HPV 11, 16 and 18 (found in 61.9%, 52.4% and 33.3% of HPV positive samples respectively). 88.9% of the lesions biopsied were from HIV positive patients, of whom 56.4% had a CD4 + count of < 200 cells/µL. A lower median CD4 + count was detected among HIV positive patients with invasive squamous cell carcinoma compared to those with moderate dysplasia (p < 0.0198). CONCLUSIONS: There is a high prevalence of HPV in OSSN in South Africa. Certain subtypes namely, 11, 16, 18, 31, 33 and 35 may be more carcinogenic. HIV with HPV co-infection may be linked as a causative factor in the development of OSSN.

Bacterial meningitis in Africa.

Bacterial meningitis differs globally, and the incidence and case fatality rates vary by region, country, pathogen, and age group; being a life-threatening disease with a high case fatality rate and long-term complications in low-income countries. Africa has the most significant prevalence of bacterial meningitis illness, and the outbreaks typically vary with the season and the geographic location, with a high incidence in the meningitis belt of the sub-Saharan area from Senegal to Ethiopia. Streptococcus pneumoniae (pneumococcus) and Neisseria meningitidis (meningococcus) are the main etiological agents of bacterial meningitis in adults and children above the age of one. Streptococcus agalactiae (group B Streptococcus), Escherichia coli, and Staphylococcus aureus are neonatal meningitis's most common causal agents. Despite efforts to vaccinate against the most common causes of bacterial neuro-infections, bacterial meningitis remains a significant cause of mortality and morbidity in Africa, with children below 5 years bearing the heaviest disease burden. The factors attributed to this continued high disease burden include poor infrastructure, continued war, instability, and difficulty in diagnosis of bacterial neuro-infections leading to delay in treatment and hence high morbidity. Despite having the highest disease burden, there is a paucity of African data on bacterial meningitis. In this article, we discuss the common etiologies of bacterial neuroinfectious diseases, diagnosis and the interplay between microorganisms and the immune system, and the value of neuroimmune changes in diagnostics and therapeutics.

Comparing the findings and diagnostic sensitivity of cardiovascular magnetic resonance in biopsy confirmed acute myocarditis with infarct-like vs. heart failure presentation.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is considered the reference imaging modality in providing a non-invasive diagnosis of acute myocarditis (AM), as it allows for the detection of myocardial injury associated with AM. However, the diagnostic sensitivity and pattern of CMR findings appear to differ according to clinical presentation. METHODS: This is a retrospective cross-sectional study. Consecutive adult patients presenting to a single tertiary centre in South Africa between August 2017 and January 2022 with AM confirmed on endomyocardial biopsy (EMB) were enrolled. Patients with infarct-like symptoms, defined as those presenting primarily with chest pain syndrome with associated ST-T wave changes on electrocardiogram, or heart failure (HF) symptoms, defined as clinical signs and symptoms of HF without significant chest discomfort, were compared using contrasted CMR and parametric techniques with EMB confirmation of AM as diagnostic gold standard. RESULTS: Forty-one patients were identified including 23 (56%) with infarct-like symptoms and 18 (44%) with HF symptoms. On CMR, the infarct-like group had significantly higher ejection fractions of both ventricles (LVEF 55.3 ± 15.3% vs. 34.4 ± 13.5%, p < 0.001; RVEF 57.3 ± 10.9% vs. 42.9 ± 18.2%, p = 0.008), without significant differences in end diastolic volumes (LVEDVI 82.7 ± 30.3 ml/m2 vs. 103.4 ± 35.9 ml/m2, p = 0.06; RVEDVI 73.7 ± 22.1 ml/m2 vs. 83.9 ± 29.9 ml/m2, p = 0.25). Myocardial oedema was detected more frequently on T2-weighted imaging (91.3% vs. 61.1%, p = 0.03) and in more myocardial segments [3.0 (IQR 2.0-4.0) vs. 1.0 (IQR 0-1.0), p = 0.003] in the infarct-like group. Despite the absence of a significant statistical difference in the prevalence of late gadolinium enhancement (LGE) between the two groups (95.7% vs. 72.2%, p = 0.07), the infarct-like group had LGE detectable in significantly more ventricular segments [4.5 (IQR 2.3-6.0) vs. 2.0 (IQR 0-3.3), p = 0.02] and in a different distribution. The sensitivity of the original Lake Louise Criteria (LLC) was 91.3% in infarct-like patients and 55.6% in HF patients. When the updated LLC, which included the use of parametric myocardial mapping techniques, were applied, the sensitivity improved to 95.7% and 72.2% respectively. CONCLUSION: The pattern of CMR findings and its diagnostic sensitivity appears to differ in AM patients presenting with infarct-like and HF symptoms. Although the sensitivity of the LLC improved with the addition of parametric mapping in the HF group, it remained lower than that of the infarct-like group, and suggests that EMB should be considered earlier in the course of patients with clinically suspected AM presenting with HF.

Prevalence of cardiotropic viruses in adults with clinically suspected myocarditis in South Africa.

OBJECTIVES: To determine the prevalence and types of viral pathogens in the myocardium of patients presenting with clinically suspected myocarditis in South Africa. METHOD: This is a prospective cross-sectional study. Consecutive adults presenting to a single tertiary centre in South Africa between August 2017 and January 2021 who fulfilled the European Society of Cardiology's diagnostic criteria for clinically suspected myocarditis and who had undergone the appropriate investigations, including cardiac MRI (CMR) and endomyocardial biopsy (EMB), were included. RESULTS: One hundred and two patients with clinically suspected myocarditis were enrolled. Acute myocarditis (AM) was confirmed by CMR or EMB in 82 (80.39%) patients. Viral genomes were detected by PCR in EMB specimens of 50 patients with AM. Parvovirus B19 (PVB19) was the most frequently detected virus, in 37 as monoinfection and 4 as coinfection. This was followed by Epstein-Barr virus (n=6), human herpesvirus 6 (n=2) and human bocavirus (n=1). PVB19 was also detected in 9 patients with no evidence of AM on CMR or EMB. CONCLUSION: Viral myocarditis is the most common form of myocarditis in South Africa. Local viral prevalence appears to be similar those of the developed world. The clinical significance and pathogenic role of PVB19 remains questioned, and its local background prevalence will have to be further investigated.

Routine use of fluoroscopic and real-time transthoracic echocardiographic guidance to ensure safety of right ventricular endomyocardial biopsy in a low-volume center.

To determine whether the routine use of real-time transthoracic echocardiographic (TTE) guidance in addition to fluoroscopy would ensure the safety of right ventricular endomyocardial biopsy (RV EMB) in a low-volume center. RV EMB is a valuable tool and plays an important role in the diagnosis and management of patients with myocardial diseases. However, it has yet to gain widespread acceptance due to its perceived low diagnostic yield and concerns regarding its invasive nature and potential complications. Although the safety of EMB when performed by experienced operators in high-volume centers is well established, the complication rate in low-volume centers is less well defined but appears to be higher. This is a retrospective single-center cross-sectional study. Consecutive adult patients who underwent RV EMB procedures at Tygerberg Hospital (Cape Town, South Africa) between August 2017 and December 2020 were included. RV EMB was successfully performed in 85 patients. No major complications were reported. Five (5.88%) patients experienced minor complications: three transient right bundle branch blocks and two hemodynamically stable ventricular tachycardia. A definitive biopsy diagnosis was made in 37 (43.54%) patients. The average procedural time was 27.06 min, which equated to 4.09 min per specimen taken. The routine use of real-time TTE guidance in addition to fluoroscopy ensured the safety of RV EMB in a low-volume center without unnecessarily prolonging procedural time.

Nicotinic Receptors in the Brainstem Ascending Arousal System in SIDS With Analysis of Pre-natal Exposures to Maternal Smoking and Alcohol in High-Risk Populations of the Safe Passage Study.

Pre-natal exposures to nicotine and alcohol are known risk factors for sudden infant death syndrome (SIDS), the leading cause of post-neonatal infant mortality. Here, we present data on nicotinic receptor binding, as determined by 125I-epibatidine receptor autoradiography, in the brainstems of infants dying of SIDS and of other known causes of death collected from the Safe Passage Study, a prospective, multicenter study with clinical sites in Cape Town, South Africa and 5 United States sites, including 2 American Indian Reservations. We examined 15 pons and medulla regions related to cardiovascular control and arousal in infants dying of SIDS (n = 12) and infants dying from known causes (n = 20, 10 pre-discharge from time of birth, 10 post-discharge). Overall, there was a developmental decrease in 125I-epibatidine binding with increasing postconceptional age in 5 medullary sites [raphe obscurus, gigantocellularis, paragigantocellularis, centralis, and dorsal accessory olive (p = 0.0002-0.03)], three of which are nuclei containing serotonin cells. Comparing SIDS with post-discharge known cause of death (post-KCOD) controls, we found significant decreased binding in SIDS in the nucleus pontis oralis (p = 0.02), a critical component of the cholinergic ascending arousal system of the rostral pons (post-KCOD, 12.1 ± 0.9 fmol/mg and SIDS, 9.1 ± 0.78 fmol/mg). In addition, we found an effect of maternal smoking in SIDS (n = 11) combined with post-KCOD controls (n = 8) on the raphe obscurus (p = 0.01), gigantocellularis (p = 0.02), and the paragigantocellularis (p = 0.002), three medullary sites found in this study to have decreased binding with age and found in previous studies to have abnormal indices of serotonin neurotransmission in SIDS infants. At these sites, 125I-epibatidine binding increased with increasing cigarettes per week. We found no effect of maternal drinking on 125I-epibatidine binding at any site measured. Taken together, these data support changes in nicotinic receptor binding related to development, cause of death, and exposure to maternal cigarette smoking. These data present new evidence in a prospective study supporting the roles of developmental factors, as well as adverse exposure on nicotinic receptors, in serotonergic nuclei of the rostral medulla-a finding that highlights the interwoven and complex relationship between acetylcholine (via nicotinic receptors) and serotonergic neurotransmission in the medulla.

Pelvic Construct Prediction of Trabecular and Cortical Bone Structural Architecture.

The pelvic construct is an important part of the body as it facilitates the transfer of upper body weight to the lower limbs and protects a number of organs and vessels in the lower abdomen. In addition, the importance of the pelvis is highlighted by the high mortality rates associated with pelvic trauma. This study presents a mesoscale structural model of the pelvic construct and the joints and ligaments associated with it. Shell elements were used to model cortical bone, while truss elements were used to model trabecular bone and the ligaments and joints. The finite element (FE) model was subjected to an iterative optimization process based on a strain-driven bone adaptation algorithm. The bone model was adapted to a number of common daily living activities (walking, stair ascent, stair descent, sit-to-stand, and stand-to-sit) by applying onto it joint and muscle loads derived using a musculoskeletal modeling framework. The cortical thickness distribution and the trabecular architecture of the adapted model were compared qualitatively with computed tomography (CT) scans and models developed in previous studies, showing good agreement. The sensitivity of the model to changes in material properties of the ligaments and joint cartilage and changes in parameters related to the adaptation algorithm was assessed. Changes to the target strain had the largest effect on predicted total bone volumes. The model showed low sensitivity to changes in all other parameters. The minimum and maximum principal strains predicted by the structural model compared to a continuum CT-derived model in response to a common test loading scenario showed good agreement with correlation coefficients of 0.813 and 0.809, respectively. The developed structural model enables a number of applications such as fracture modeling, design, and additive manufacturing of frangible surrogates.

Surgical Treatment of a Rare "Reverse" Madelung Deformity in 11 Years Female Patient.

Madelung deformity is an abnormality of the distal part of the forearm due to a growth arrest in the distal radial physis creating an increase of the radial tilt angle associated with a dorsal subluxation of the distal ulna in most cases. It is a rare condition which represents only 1.7% of hand deformities being characterized by the presence of an abnormal structure, Vickers ligament, that tethers the distal radius to the lunate bone. Although it is believed to be a congenital disorder, the symptoms are absent till late childhood. We present a case of a 11 years old girl patient, who came to our clinic for deformity of both forearms, which consisted of an anteriorly curved radius, volar proeminence of the distal ulna, partial limitation of supination and pain in the last 6 months, with and insidious onsed and aggravated lately. The mother of the patient, at the age of 13, was diagnosed with the same deformity which was surgically treated at that time. Furthermore, the patient has an older sister with no deformity of the forearms. X-rays revealed an increased radial tilt and anterior luxation of the distal ulna. Considering the deformity and the presence of pain we decided to excise the Vickers ligament and make an opening and derotation wedge osteotomy of the distal radius.

Mitochondrial impairment observed in fibroblasts from South African Parkinson's disease patients with parkin mutations.

Parkinson's disease (PD), defined as a neurodegenerative disorder, is characterized by the loss of dopaminergic neurons in the substantia nigra in the midbrain. Loss-of-function mutations in the parkin gene are a major cause of autosomal recessive, early-onset PD. Parkin has been implicated in the maintenance of healthy mitochondria, although previous studies show conflicting findings regarding mitochondrial abnormalities in fibroblasts from patients harboring parkin-null mutations. The aim of the present study was to determine whether South African PD patients with parkin mutations exhibit evidence for mitochondrial dysfunction. Fibroblasts were cultured from skin biopsies obtained from three patients with homozygous parkin-null mutations, two heterozygous mutation carriers and two wild-type controls. Muscle biopsies were obtained from two of the patients. The muscle fibers showed subtle abnormalities such as slightly swollen mitochondria in focal areas of the fibers and some folding of the sarcolemma. Although no differences in the degree of mitochondrial network branching were found in the fibroblasts, ultrastructural abnormalities were observed including the presence of electron-dense vacuoles. Moreover, decreased ATP levels which are consistent with mitochondrial dysfunction were observed in the patients' fibroblasts compared to controls. Remarkably, these defects did not manifest in one patient, which may be due to possible compensatory mechanisms. These results suggest that parkin-null patients exhibit features of mitochondrial dysfunction. Involvement of mitochondria as a key role player in PD pathogenesis will have important implications for the design of new and more effective therapies.

A study of meningiomas in South Africa: investigating a correlation between clinical presentation, histopathology and genetic markers.

OBJECTIVE: To determine whether there are certain genetic markers which correlate with particular clinical characteristics of meningiomas including multiplicity, recurrence and calvarial erosion. METHODS: Thirty-eight South African-born patients with meningiomas were recruited for this study. At surgery, blood and tumour specimens were obtained for histopathological, cytogenetic and molecular analysis. Loss of heterozygosity (LOH) on chromosomes 1p and 22q were investigated and the NF2 gene on 22q12.2 was screened for disease-causing mutations. RESULTS: The commonest tumour locations were convexity (25%) and parasagittal (21%). The histology results showed that 86.8% of the patients had Grade I tumours and the remainder had Grade II tumours. A pathogenic nonsense mutation, R341X in the NF2 gene was found in only one patient. LOH on each of chromosomes 1p and 22q was observed in 44.7% of patients, but in different individuals. Significant associations were found between having specific tumour characteristics and both male gender (p-value = 0.0059) and 22q LOH (p-value = 0.0425). We estimated that having 22q LOH makes an individual approximately four times more likely to develop a tumour that exhibits multiplicity, recurrence or calvarial erosion (OR = 4.8; 95% CI: 1.2-23.4). Adjusting for gender strengthened this effect (OR = 6.1; 95% CI: 1.1-48.7). CONCLUSIONS: Our data indicate that male patients and patients with a meningioma that has 22q LOH are more likely to develop tumours exhibiting multiplicity, recurrence or calvarial erosion. We recommend that this subset of patients should be followed up more closely. Further study is needed to determine the benefit of adjuvant radiation therapy in this scenario.