Which side are they on? Diagnosing primary ciliary dyskinesias in low- or middle-income countries: A review and case series.

Background: Primary ciliary dyskinesia (PCD) is a rare genetic condition with a variable clinical presentation, making its diagnosis a challenge. We describe two unrelated sibling pairs with PCD: adult siblings in the first and perinatal/neonatal in the second. Both families highlight the more common and rarer clinical manifestations of PCD. We use these cases to highlight: (i) current understanding of the underlying genetic and pathophysiological mechanisms of PCD; (ii) the diversity of cardiac and respiratory features of PCD across a wide age range; (iii) aspects of the history and clinical examination that should raise suspicion of PCD; and (iv) the role of next-generation sequencing gene panel testing in confirmation of the diagnosis. We note genomic evidence predicting that PCD is relatively common in black African populations. Study synopsis: What the study adds. This review of two sibling pairs illustrates the variable histories, presentations, diagnostic processes and clinical courses of primary ciliary dyskinesia (PCD) in low- or middle-income countries (LMICs), highlighting the diagnostic challenges faced when encountering such patients in settings where there may not be access to specialised resources. Possible diagnostic tools that can be used are discussed, weighing up their pros and cons in an LMIC setting, and a potential diagnostic approach that can be adapted to the treating clinician's own context is provided.Implications of the findings. Confirmation of the diagnosis of primary ciliary dyskinesia is no longer limited to well-resourced institutions, but can be done in less specialised environments using novel, highly accurate next-generation sequencing gene panel testing, reducing the need to transport patients as well as the overall cost to the healthcare system. Well-resourced institutions that see high volumes of patients with PCD can invest in new highly sensitive diagnostic tools such as high-speed video microscopy. There is a need for research investigating the validity of tools such as ciliary immunofluorescence in the South African population.

The mortality rate of patients with open abdomen and contributing factors - a three-year audit in a major academic trauma unit.

BACKGROUND: Damage control surgery (DCS) is a widely used approach in trauma. An open abdomen carries complications, increased morbidity and mortality. This study aims to quantify the mortality rate, determine contributory factors and factors influencing the decision to perform DCS and assess morbidity in patients undergoing open abdomen. METHODS: A retrospective review was conducted on 205 patients in Charlotte Maxeke Johannesburg Academic Hospital Trauma Unit. The mortality rate was evaluated over a 24-hour, 7-day and 28-day period. Data were collected by a data collection sheet from 1 January 2016 to 31 December 2018. RESULTS: Of the 205 patients, 193 were male and the median age was 34.34 years. Penetrating trauma was the most predominant mechanism of injury in 162 (79%), with gunshot injuries seen in the majority (130/162). The mortality rate was 55/205 (26.8%) for open abdomen patients, 19/55 (34.5%) within the first 24 hours, 22/55 (40%) in the 24-hours to 7-days period, and 14/55 (25.4%) in the 8-day to 28-day period. Statistically significant factors contributing to mortality were haemodynamic instability, hypothermia, coagulopathy, massive transfusion, vasopressors, and significant associated injuries. Morbidities were entero-atmospheric fistula (EAF) in 7.3% (Clavien-Dindo grade IIIa), surgical site infection in 45.3% (Clavien-Dindo grade I) and ventral hernia in 10.24% (Clavien-Dindo grade IIIb). CONCLUSION: Most open abdomens were performed in males, with gunshot injuries being the most common mechanism. The majority of mortalities were within the 24-hours to 7-days period. The most common morbidity associated with an open abdomen was surgical site infection.

Core competencies in critical care for general medical practitioners in South Africa: A Delphi study.

Background: Despite a high burden of disease that requires critical care services, there are a limited number of intensivists in South Africa (SA). Medical practitioners at district and regional public sector hospitals frequently manage critically ill patients in the absence of intensivists, despite these medical practitioners having had minimal exposure to critical care during their undergraduate training. Objectives: To identify core competencies in critical care for medical practitioners who provide critical care services at public sector hospitals in SA where intensivists are not available to direct patient management. Methods: A preliminary list of core competencies in critical care was compiled. Thereafter, 13 national and international experts were requested to achieve consensus on a final list of core competencies that are required for critical care by medical practitioners, using a modified Delphi process. Results: A final list of 153 core competencies in critical care was identified. Conclusion: The core competencies identified by this study could assist in developing training programmes for medical practitioners to improve the quality of critical care services provided at district and regional hospitals in SA. Contribution of the study: The study provides consensus on a list of core competencies in critical care that non-intensivist medical practitioners managing critically ill patients in healthcare settings in South Africa, especially where intensivists are not readily available, should have. The list can form the core content of training programmes aimed at improving critical care competence of general medical practitioners, and in this way hopefully improve the overall outcomes of critically ill patients in South Africa.

The characteristics and costs of severe theophylline toxicity in a tertiary critical care unit in Eastern Cape Province, South Africa.

BACKGROUND: Severe theophylline toxicity requiring haemodialysis accounts for approximately one-third of drug toxicity cases admitted to the Livingstone Tertiary Hospital (LTH) intensive care unit (ICU) in Gqeberha, South Africa, imposing a significant resource burden. OBJECTIVES: To investigate the characteristics and burden of severe theophylline toxicity in an Eastern Cape Province tertiary hospital adult ICU. METHODS: A retrospective review of all severe theophylline toxicity admissions to the ICU from 1 January 2013 to 31 December 2018 was conducted. Demographic and clinical data were captured and analysed. The National Department of Health 2019 fees schedule was used to calculate costs based on duration of ICU stay and number of haemodialysis sessions received. RESULTS: Of the 57 patients included in the study, 84% were cases of deliberate self-harm. The majority were aged <40 years (77%) and female (79%). The mean (standard deviation (SD)) initial serum theophylline level was 612 (269) µmol/L. Complications included convulsions (n=12; 21%), arrhythmias (n=9; 16%), need for mechanical ventilation (n=7; 12%) and death (n=4; 7%). The main risk factors for these complications were age ≥30 years, an inappropriately normal or elevated initial serum potassium level, an elevated serum creatinine kinase level and an elevated initial serum theophylline level. Receiver operator characteristic curve analysis assessing the initial serum theophylline level as a discriminator for life-threatening complications produced an area under the curve of 0.71 for serum theophylline >400 µmol/L (sensitivity 88%, specificity 12%). All the 4 patients who died had an initial serum theophylline level >1 000 µmol/L. The mean (SD) cost per admission amounted to ZAR16 897 (10 718), with a mean of one 4-hour dialysis session per admission. CONCLUSION: Severe theophylline toxicity, usually in the context of  deliberate self-harm, is a preventable yet life-threatening toxicity encountered at  LTH.  Demographic  risk factors include young females from certain areas in and around Gqeberha.  Risk factors for complications include older age, paradoxically normal or elevated serum potassium levels, elevated serum creatinine kinase levels and an initial serum theophylline level >400 µmol/L. Patients with these clinical features should be closely monitored and treated timeously at an appropriate level of care. The need for ICU admission and dialysis, both limited resources, makes the treatment of severe theophylline toxicity costly. Further studies of the underlying psychosocial drivers, local prescribing practices and preventive interventions related to severe theophylline toxicity are required.

Quantifying the burden of the post-ICU syndrome in South Africa: A scoping review of evidence from the public health sector.

Background: The post-ICU syndrome (PICS) comprises unexpected impairments in physical, cognitive, and mental health after intensive care unit (ICU) discharge, and is associated with a diminished health-related quality of life (HRQOL). A Cochrane review recommended more research in this field from low- and middle-income countries. Objectives: This review aims to examine the extent and nature of publications in the field of PICS in the South African (SA) public health sector. Findings of available local research are contextualised through comparison with international data. Methods: A comprehensive literature search strategy was employed. Inclusion criteria comprised publications enrolling adult patients following admission to SA public hospital ICUs, with the aim to study the main elements of PICS (ICU-acquired neuromuscular weakness, neurocognitive impairment, psychopathology and HRQOL). Results: Three studies investigated physical impairment, 1 study psychopathology, and 2 studies HRQOL. Recommended assessment tools were utilised. High rates of attrition were reported. Neuromuscular weakness in shorter-stay patients had recovered at 3 months. Patients who were ventilated for ≥5 days were more likely to be impaired at 6 months. The study on psychopathology reported high morbidity. The HRQOL of survivors was diminished, particularly in patients ventilated for ≥5 days. Conclusion: This review found a paucity of literature evaluating PICS in the SA public health sector. The findings mirror those from international studies. Knowledge gaps pertaining to PICS in medical, surgical and HIV-positive patients in SA are evident. No publications on neurocognitive impairment or the co-occurrence of PICS elements were identified. There is considerable scope for further research in this field in SA. Contributions of the study: This review identified the available publications investigating the post ICU syndrome (PICS) in the South African public healthcare setting. A small number of ground-breaking studies were found. Knowledge gaps in this field were identified.

Prediction of in-hospital mortality: An adaptive severity-of-illness score for a tertiary ICU in South Africa.

Background: A scoring system based on physiological conditions was developed in 1984 to assess the severity of illness. This version, and subsequent versions, were labelled Simplified Acute Physiology Scores (SAPS). Each extension addressed limitations in the earlier version, with the SAPS III model using a data-driven approach. However, the SAPS III model did not include data collected from the African continent, thereby limiting the generalisation of the results. Objectives: To propose a scoring system for assessing severity of illness at intensive care unit (ICU) admission and a model for prediction of in-hospital mortality, based on the severity of illness score. Methods: This is a prospective cohort study which included patients who were admitted to an ICU in a South African tertiary hospital in 2017. Logistic regression modelling was used to develop the proposed scoring system, and the proposed mortality prediction model. Results: The study included 829 patients. Less than a quarter of patients (21.35%; n=177) died during the study period. The proposed model exhibited good calibration and excellent discrimination. Conclusion: The proposed scoring system is able to assess severity of illness at ICU admission, while the proposed statistical model may be used in the prediction of in-hospital mortality. Contributions of the study: This study is the first to develop a model similar to the SAPS III model, based on data collected in South Africa. In addition, this study provides a potential starting point for the development of a model that can be used nationally.

Long-stay medical-surgical intensive care unit patients in South Africa: Quality of life and mortality 1 year after discharge.

BACKGROUND: Although mortality is the primary measure of critical care outcome, the health-related quality of life (HRQOL) of survivors is often diminished. There is a paucity of South African research on HRQOL in intensive care unit (ICU) survivors. OBJECTIVES: To evaluate the 1-year post-discharge data of long-stay ICU patients, a group known to consume 20 - 40% of ICU resources. METHODS: A 1-year prospective observational study was conducted in a multidisciplinary medical-surgical ICU. Adult patients who were mechanically ventilated beyond 6 days were included. Clinical and mortality data were collected. Pre-admission and 6- and 12-month HRQOL were measured with the Short Form-36 questionnaire. Physical and mental component summary scores (PCS and MCS) were calculated. Associations between 12-month mortality and poor HRQOL scores were determined. RESULTS: Of 119 patients enrolled, 40.3% had sustained trauma, 19.3% were post-surgical and 40.3% had medical conditions; 29.2% were HIV-positive (HIV status was known for 74.8% of the cohort). The hospital and 12-month mortality rates were 42.9% and 57.4% (n=66/115), respectively. Age, longer ICU stay, higher disease severity scores and vasopressor use were associated with 12-month mortality. The survivors' median PCS and MCS at 6 and 12 months were significantly lower compared with pre-admission scores (both p<0.001). At 12 months, 53.1% of survivors demonstrated a poor PCS and 42.9% a poor MCS. Associations with poor 12-month PCS included longer ICU stay, male gender and trauma, while trauma and sepsis were associated with a poor 12-month MCS. Among the 19 trauma survivors, 78.9% had a poor MCS and/or PCS. Of previously employed patients, 54.8% were unemployed at 12 months. CONCLUSIONS: Patients ventilated beyond 6 days in a multidisciplinary ICU had a high mortality. Poor HRQOL at 12 months post discharge was frequently observed among survivors. Trauma was associated with poor 12-month outcomes. These findings highlight the need to further explore the outcomes of long-stay ICU patients in Africa.

Scope and mortality of adult medical ICU patients in an Eastern Cape tertiary hospital.

Background: The characteristics and mortality outcomes of patients admitted to South African intensive care units (ICUs) owing to medical conditions are unknown. Available literature is derived from studies based on data from high-income countries. Objectives: To determine ICU utilisation by medical patients and evaluate the scope of admissions and clinical associations with hospital mortality in ICU patients 12 years and older admitted to an Eastern Cape tertiary ICU, particularly in the subset with HIV disease. Methods: A retrospective descriptive one-year cohort study. Data were obtained from the LivAKI study database and demographic data, comorbidities, diagnosis, and mortality outcomes and associations were determined. Results: There were 261 (29.8%) medical ICU admissions. The mean age of the cohort was 40.2 years; 51.7% were female. When compared with the surgical emergencies, the medical subgroup had higher sequential organ failure assessment (SOFA) scores (median score 5 v. 4, respectively) and simplified acute physiology score III (SAPS 3) scores (median 52.7 v. 48.5), a higher incidence of acute respiratory distress syndrome (ARDS) (7.7% v. 2.9%) and required more frequent dialysis (20.3% v. 5.5%). Of the medical admissions, sepsis accounted for 32.4% of admission diagnoses. The HIV seroprevalence rate was 34.0%, of whom 57.4% were on antiretroviral therapy. ICU and hospital mortality rates were 11.1% and 21.5% respectively, while only acute kidney injury (AKI) and sepsis were independently associated with mortality. The HIV-positive subgroup had a higher burden of tuberculosis (TB), higher admission SOFA and SAPS 3 scores and required more organ support. Conclusion: Among medical patients admitted to ICU, there was a high HIV seroprevalence with low uptake of antiretroviral therapy. Sepsis was the most frequently identified ICU admission diagnosis. Sepsis and AKI (not HIV) were independent predictors of mortality. Co-infection with HIV and TB was associated with increased mortality. Contributions of the study: The epidemiology and outcomes of adults who are critically ill from medical conditions in South African intensive care units was previously unknown but has been described in this study. The association of sepsis, TB, HIV and acute kidney injury with mortality is discussed.

Advances in imaging the blood and aqueous vessels of the ocular limbus.

The vessels of the limbus play a pivotal role in the drainage of the major portion of aqueous humour from the anterior chamber. Aberrations in the limbal architecture can lead to raised intraocular pressure, which in turn can lead to blinding conditions such as glaucoma. Imaging these vessels in the normal eye, in development, and in conditions where there is anterior segment dysgenesis remains a challenge. Here we review the progress in limbal vessel imaging in the past 50 years and provide key information on their strengths and limitations. Included is an analysis of serial histological sectioning, ultrathin sections, microvascular perfusion with plastics and corrosion casting, X-ray microcomputed tomography, in vivo imaging including analysis of transgenic mice expressing GFP-vascular endothelium fusion proteins, in vivo microscopy imaging using fluorescent-labelled antibodies, slit-lamp microscopy and gonioscopy, fluorescein angiography, optical coherence tomography, and various labelling procedures for the vascular endothelium and the various forms of microscopy used to view these.

The colonic groove or furrow: a comparative morphological study of six species of African mole-rats (Rodentia, Bathyergidae).

Herbivorous mammals such as nutrias, guinea pigs, chinchillas, and mole-rats have a longitudinal mucosal colonic groove (furrow) in their ascending colon, which is thought to play a role in the colonic separation mechanism (CSM). It is not known whether this groove is structurally modified to adapt to this function in mole-rat species. The morphology of this groove was studied in 32 mol-rats, four species, one of which consisted of three subspecies, endemic to southern Africa and two species found in eastern Africa. The macroscopic morphology of the groove was documented, and samples for histological examination were taken. The groove was wide at its origin at the cecocolic junction and was lined on either side by a row of papillae with the opposing papillae slightly offset in arrangement. The papillated groove gradually decreased in size toward the distal part of the ascending colon where it disappeared. This pattern was similar in all species except in Heterocephalus glaber, where the papillae were absent and the groove was lined by two longitudinal ridges. A histological examination of cross sections revealed that the mucosa covering the inner and outer walls of the groove was rich in mucous-secreting goblet cells. The walls of the groove contained smooth muscle extending from the inner circular smooth muscle layer at the base to the tips of the papillae in all species examined as well as arteries, lymphatic vessels, and prominent sinusoid-like veins. The groove could be demonstrated both macroscopically and histologically in three Bathyergus suillus fetuses of varying sizes. The sinusoid-like veins present in all grooves, regardless of macroscopic shape, suggest that they have a role in the functioning of the groove.

The synthesis and anticancer activity of selected diketopiperazines.

Six selected diketopiperazines, cyclo(Gly-Val), cyclo(Gly-D-Val), cyclo(Gly-Leu), cyclo(Gly-Ile), cyclo(Phe-Cys) and cyclo(Tyr-Cys), were synthesized via various synthetic routes. Their potential to inhibit cancer cell growth in HT-29, HeLa and MCF-7 cells was determined. Cyclo(Tyr-Cys) caused the greatest inhibition in cervical carcinoma cells with near equivalent activity against HT-29 and MCF-7 cells. The other cyclic dipeptides tested were effective in the inhibition of colon, cervical and breast carcinoma cells, respectively, but the percentage inhibition was lower than for cyclo(Tyr-Cys).

The topography and gross anatomy of the gastrointestinal tract of the Cape dune mole-rat (Bathyergus suillus).

The Cape dune mole-rat, Bathyergus suillus, is the largest truly subterranean rodent in the world and is restricted to sandy soil areas of the southern and South-western Cape Province. These animals are herbivorous, feeding mostly on the below ground portions of grass and geophytes. The present study was undertaken to explore whether there are any gross anatomical gastrointestinal adaptations associated with the herbivorous diet of the Cape dune mole-rat and to provide a basis for further investigations into the nutrition and ecology of this animal. The stomach was unilocular (simple) and the entire internal aspect displayed macroscopically visible glandular epithelium. The caecum was voluminous and arranged into a spiral of approximately one and a half turns. The tip of the caecum resembled a vermiform appendix and lay against the left lateral abdominal wall. The ascending colon consisted of proximal and distal portions, arranged in a large double loop and attached to each other by a fat-filled mesenteric fold. The looped, folded ascending colon filled the right side of the abdominal cavity, lying against the right dorsal, lateral and ventral abdominal wall. The internal structure of the ascending colon revealed a shallow groove, lined on either side by a row of papillae. The simple, glandular stomach in conjunction with a prominent caecum and a greatly enlarged ascending colon suggests that this animal is a hindgut fermenting herbivore, rather than a caecal fermenter, as is the case in most rodent species.

Helicobacter pylori lipopolysaccharide stimulates gastric mucosal pepsinogen secretion.

The effect of Helicobacter pylori lipopolysaccharide on guinea pig gastric mucosal pepsinogen secretion has been examined using an Ussing chamber technique. Luminal addition of H. pylori lipopolysaccharide resulted in a fifty-fold stimulation of pepsinogen secretion compared to a twelve-fold increase with E. coli lipopolysaccharide. Electron microscopy showed marked degranulation of zymogen granules but no evidence of chief cell disruption.

Exposure of surgeons-in-training to radiation during intramedullary fixation of femoral shaft fractures.

Owing to the continuous turnover of registrars and radiographers, most of the trauma-related orthopaedic surgery in this academic hospital is done by inexperienced surgeons-in-training and the fluoroscopy by junior radiographers. This could result in excessive radiation doses. Calibrated lithium fluoride thermoluminescent chips were secured to various parts of the primary surgeon's body to quantify the radiation dose received during the insertion of an intramedullary nail. Closed intramedullary fixation of 15 fractures of the femur was done with interlocking as necessary. The total average exposure time was 14 minutes 45 seconds per procedure. Distal locking took up 31% of this time. The mean radiation dose to the surgeon's eyes and thyroid was 0.13 mGy and to the dominant hand 2.10 mGy. This would allow the performance of about 350 such procedures per year before the maximum permissible dose level was reached. Recommendations to decrease irradiation dosage are made.

The leaded apron revisited: does it reduce gonadal radiation dose in dental radiology?

A tissue-equivalent anthropomorphic human phantom was used with a lithium fluoride thermoluminescent dosimetry system to evaluate the radiation absorbed dose to the ovarian and testicular region during dental radiologic procedures. Measurements were made with and without personal lead shielding devices consisting of thyroid collar and apron of 0.25 mm lead thickness equivalence. The radiation absorbed dose with or without lead shielding did not differ significantly from control dosimeters in vertex occlusal and periapical views (p greater than 0.05). Personal lead shielding devices did reduce gonadal dose in the case of accidental exposure (p less than 0.05). A leaded apron of 0.25 mm lead thickness equivalent was permeable to radiation in direct exposure testing.

Ultrastructural correlates of ischaemic contracture during global subtotal ischaemia in the rat heart.

The development of left ventricular ischaemic contracture and its correlation with ultrastructural and sarcolemmal permeability defects were studied in isolated rat hearts during global subtotal ischaemia. With acetate as substrate the hearts exhibited a rise in diastolic tension after 8-10 min at which time small foci of contracted myocytes were scattered throughout the myocardium. In hearts with 5% of the maximum diastolic tension (termed 5% contracture), the foci were situated predominantly in the subendocardium and papillary muscle. Contracted myocytes in these foci were capable of excluding ionic lanthanum thus demonstrating retention of normal sarcolemmal permeability properties. With 30% contracture ultrastructural damage had spread to the subepicardium and with further contracture there was an associated increase in the number and size of foci in all regions. In these foci, swelling of the tubular sarcolemmal system and occasionally of the sarcoplasmic reticulum appeared to precede myofibrillar contraction. At 50% contracture lanthanum influx into contracted cells became more frequent. Hearts developed full contracture by 15-18 min at which time most myocytes were contracted and retained lanthanum intracellularly. The heterogeneity of the response at a cellular level may offer a possible explanation for the lack of correlation between contracture and tissue ATP. A possible sequence of structural injury leading to impaired calcium homeostasis is also suggested.

Islet cell function in long-term surviving primates after segmental pancreatic allotransplantation.

Islet cell function was studied in pancreatectomized primates with functioning segmental pancreatic allografts more than 100 days after transplantation. Segmental allograft recipients were immunosuppressed with total lymphoid irradiation (TL1) and cyclosporine (CSA). After 100 days, islet function was assessed, at which stage immunosuppression was terminated. Glucose, insulin, glucagon, and C-peptide response was assessed during intravenous glucose tolerance test (IVGTT) and during arginine and tolbutamide stimulation. In eight normoglycaemic primates in which immunosuppressive treatment had been stopped and with mean graft survival of 145 days, islet stimulation was associated with moderate glucose intolerance, reduced K-values, hypoinsulinaemia, and low C-peptide values. Postmortem findings in all animals intentionally killed revealed severe graft atrophy in the absence of significant rejection. Severe graft atrophy in normoglycaemic primates, together with significantly impaired graft function after segmental pancreatic transplantation compared to normal animals, suggest that transplantation of the whole pancreas may be mandatory if normal or near-normal function is to be achieved.

Prolongation of segmental and pancreaticoduodenal allografts in the primate with total-lymphoid irradiation and cyclosporine.

The prolongation of segmental and pancreaticoduodenal allografts (PDA) by total lymphoid irradiation (TLI) and in combination with cyclosporine (CsA) was assessed in a well established total pancreatectomy, diabetic, primate transplantation model. Pancreatic transplantation was performed in 119 pancreatectomized baboons (Papio ursinus). Of a total of 109 allografts performed, 71 were segmental allografts (open duct drainage) and 38 PDA. Of 119 graft recipients, 10 received segmental pancreatic autografts. TLI and CsA administered separately to segmental allograft recipients resulted in modest allograft survival and indefinite graft survival was not observed. 8 of 17 (47%) segmental allograft recipients that received TLI and CsA had graft survival beyond 100 days, indicating highly significant pancreatic allograft survival. All long-term segmental allograft recipients were rendered normoglycemic (plasma glucose less than 8 mmol/L) by this immunosuppressive regimen. In contrast, poor results were observed in PDA recipients treated with TLI and CsA. Mean survival in 18 treated PDA recipients was 23.8 days, 8 survived longer than 20 days (44.4%), and 1 greater than 100 days (5.5%). Despite treatment, early rejection of the duodenum in PDA recipients frequently resulted in necrosis and perforation and contributed to a high morbidity and mortality. This study indicates that, in contrast to the significant prolongation of segmental allografts by TLI and CsA, poor immunosuppression was achieved by this regimen in PDA recipients and was associated with a high morbidity and mortality caused by early rejection of the duodenum.