Surgical treatment for 'brain compartment syndrome' in children with severe head injury

OBJECTIVES: Traumatic brain injury accounts for a high percentage of deaths in children. Raised intracranial pressure (ICP) due to brain swelling within the closed compartment of the skull leads to death or severe neurological disability if not effectively treated. We report our experience with 12 children who presented with cerebral herniation due to traumatic brain swelling in whom decompressive craniectomy was used as an emergency. DESIGN: Prospective, observational. SETTING: Red Cross Children's Hospital. SUBJECTS: Children with severe traumatic brain injury and cerebral swelling. OUTCOME MEASURES: Computed tomography (CT) scanning, ICP control, clinical outcome. RESULTS: Despite the very poor clinical condition of these children preoperatively, aggressive management of the raised pressure resulted in unexpectedly good outcomes. CONCLUSION: Aggressive surgical measures to decrease ICP in the emergency situation can be of considerable benefit; the key concepts are selection of appropriate patients and early intervention

Paediatric nonbronchoscopic bronchoalveolar lavage: Overview and recommendations for clinical practice

NB-BAL is an effective procedure for the diagnosis of pulmonary disease processes in ventilated infants and children. This procedure is, however, not without risks to both patients and staff. Numerous complications of NB-BAL exist, with hypoxia being the most common. As a result, care should be taken in performing NB-BAL on haemodynamically unstable patients; patients with coagulation defects; and patients with cardiac or brain abnormalities. This paper presents an overview of paediatric nonbronchoscopic bronchoalveolar lavage (NB-BAL) including: the rationale for NB-BAL; the complications associated with the procedure; indications and contraindications. It also recommends an evidence-based clinical guideline for performing the procedure in the paediatric intensive care unit. By following the NB-BAL guidelines presented in this paper, one can ensure that an effective specimen is obtained from the lower respiratory tract, whilst minimising the risk to the patient

COVID-19: Experience of a tertiary children’s hospital in Western Cape Province, South Africa

The COVID-19 pandemic necessitated rapid changes in healthcare systems and at Red Cross War Memorial Children’s Hospital (RCWMCH), Cape Town, South Africa. Paediatric services in particular required adjustment, not only for the paediatric patients but also for their carers and the staff looking after them. Strategies were divided into streams, including the impact of COVID-19 on the hospital and the role of RCWMCH in Western Cape Province, communication strategies, adaptation of clinical services at the hospital, specifically with a paediatric-friendly approach, and staff engagement. Interventions utilised: (i) Specific COVID-19 planning was required at a children’s hospital, and lessons were learnt from other international children’s hospitals. A similar number of patients and staff were infected by the virus (244 patients and 212 staff members by 21 December 2020). (ii) Measures were put in place to assist creation of capacity at metro hospitals’ adult services by accepting children with emergency issues directly to RCWMCH, as well as accepting adolescents up to age 18 years. (iii) The communication strategy was improved to include daily engagement with heads of departments/supervisors by earlymorning structured information meetings. There were also changes in the methods of communication with staff using media such as Zoom, MS Teams and WhatsApp. Hospital-wide information and discussion sessions were held both on social platforms and in the form of smallgroup physical meetings with senior hospital administrators (with appropriate distancing). Labour union representatives were purposefully directly engaged to assess concerns. (iv) Clinical services at the hospital were adapted. These included paediatric-friendly services and physical changes to the hospital environment. (v) Staff engagement was particularly important to assist in allaying staff anxiety, developing a staff screening programme, and provision and training in use of personal protective equipment, as well as focusing on staff wellness. In conclusion, visible management and leadership has allowed for flexibility and adaptability to manage clinical services in various contexts. It is important to utilise staff in different roles during a crisis and to consider the different perspectives of people involved in the services. The key to success, that included very early adoption of the above measures, has been hospital staff taking initiative, searching for answers and identifying and implementing solutions, effective communication, and leadership support. These lessons are useful in dealing with second and further waves of the COVID-19 pandemic

Cytosolic chaperones influence the fate of a toxin dislocated from the endoplasmic reticulum

The plant cytotoxin ricin enters target mammalian cells by receptor-mediated endocytosis and undergoes retrograde transport to the endoplasmic reticulum (ER). Here, its catalytic A chain (RTA) is reductively separated from the cell-binding B chain, and free RTA enters the cytosol where it inactivates ribosomes. Cytosolic entry requires unfolding of RTA and dislocation across the ER membrane such that it arrives in the cytosol in a vulnerable, nonnative conformation. Clearly, for such a dislocated toxin to become active, it must avoid degradation and fold to a catalytic conformation. Here, we show that, in vitro, Hsc70 prevents aggregation of heat-treated RTA, and that RTA catalytic activity is recovered after chaperone treatment. A combination of pharmacological inhibition and cochaperone expression reveals that, in vivo, cytosolic RTA is scrutinized sequentially by the Hsc70 and Hsp90 cytosolic chaperone machineries, and that its eventual fate is determined by the balance of activities of cochaperones that regulate Hsc70 and Hsp90 functions. Cytotoxic activity follows Hsc70-mediated escape of RTA from an otherwise destructive pathway facilitated by Hsp90. We demonstrate a role for cytosolic chaperones, proteins typically associated with folding nascent proteins, assembling multimolecular protein complexes and degrading cytosolic and stalled, cotranslocational clients, in a toxin triage, in which both toxin folding and degradation are initiated from chaperone-bound states

Cytosolic chaperones influence the fate of a toxin dislocated from the endoplasmic reticulum

The plant cytotoxin ricin enters target mammalian cells by receptor-mediated endocytosis and undergoes retrograde transport to the endoplasmic reticulum (ER). Here, its catalytic A chain (RTA) is reductively separated from the cell-binding B chain, and free RTA enters the cytosol where it inactivates ribosomes. Cytosolic entry requires unfolding of RTA and dislocation across the ER membrane such that it arrives in the cytosol in a vulnerable, nonnative conformation. Clearly, for such a dislocated toxin to become active, it must avoid degradation and fold to a catalytic conformation. Here, we show that, in vitro, Hsc70 prevents aggregation of heat-treated RTA, and that RTA catalytic activity is recovered after chaperone treatment. A combination of pharmacological inhibition and cochaperone expression reveals that, in vivo, cytosolic RTA is scrutinized sequentially by the Hsc70 and Hsp90 cytosolic chaperone machineries, and that its eventual fate is determined by the balance of activities of cochaperones that regulate Hsc70 and Hsp90 functions. Cytotoxic activity follows Hsc70-mediated escape of RTA from an otherwise destructive pathway facilitated by Hsp90. We demonstrate a role for cytosolic chaperones, proteins typically associated with folding nascent proteins, assembling multimolecular protein complexes and degrading cytosolic and stalled, cotranslocational clients, in a toxin triage, in which both toxin folding and degradation are initiated from chaperone-bound states

Characteristics and outcome of long-stay patients in a paediatric intensive care unit in Cape Town, South Africa

Background. Paediatric intensive care is a costly, specialised and limited resource in low- and middle-income countries. The implications of extended paediatric intensive care unit (PICU) stay in South Africa (SA) are not known.Objectives. To describe the characteristics, outcomes and resource consumption of long-stay patients (LSPs) and to identify predictive factors for long PICU stay.Methods. A retrospective review of routinely collected data on all children admitted to an SA PICU over one calendar year. Long PICU stay was defined statistically as >19 days. Long- and short-stay patient (SSP) groups were compared, and variables significantly associated with long stay on univariate analysis were entered into a stepwise multiple regression model.Results. Over the study period, 1 126 children (median age 8 months, 60.9% male) were admitted to the PICU, occupying 5 936 bed-days; 54  LSPs (4.8%) utilised 1 807 (30.4%) bed-days. Mortality and the standardised mortality ratio (actual/mean predicted mortality) in LSPs and SSPs were 29.6% v. 12% (p=0.002) and 2.4 v. 0.7 (p=0.002), respectively. Median duration of stay for LSPs and SSPs was 29.5 days and 2 days, respectively (p<0.0001). LSPs were younger than SSPs (median 4 months (interquartile range 2 - 17) v. 9 months (2 - 34); p=0.03), and fewer were male (48% v. 61.6%, p=0.049). On multivariate analysis, only female gender was independently associated with long PICU stay.Conclusions. LSPs represent a small proportion of PICU admissions, yet have a higher mortality rate than SSPs and consume disproportionate PICU resources. No predictive model could be established for early recognition of potential LSPs to plan PICU bed allocation effectively

Parental satisfaction with the quality of care in a South African paediatric intensive care unit

Background. The quality of family-centred care in the paediatric intensive care unit (PICU) has been poorly studied in South Africa (SA). Objective. To explore parents' satisfaction with care in a PICU in SA. Methods. A prospective descriptive survey study was conducted among a convenience sample of 100 parents of children admitted to the PICU for ≥48 hours. Participants completed the EMpowerment of PArents in THe Intensive Care (EMPATHIC-30) questionnaire, which includes 30 closed questions rating satisfaction in different domains and four open-ended questions to qualitatively describe PICU experiences. Results. Of the 100 admissions included in the study, 35% were unplanned and 88% were mechanically ventilated. Parents were very satisfied with the quality of PICU care, with mean scores in all domains reaching ≥5.5 on a 6-point Likert scale. Parents were most satisfied with the professional attitude of PICU staff, whereas the lowest scores were seen in the 'Information' and 'Parental participation' domains. The internal consistency (Cronbach's α) associated with the different domains ranged between 0.25 (Parental participation) and 0.59 (Care and cure). The need for communication and support during the admission period, and the importance of environmental factors, proximity to the child, the attitude of medical staff and social support during the PICU stay emerged as common themes from the responses to the open-ended questions. Conclusion. Although parents were generally well satisfied with the quality of care, improving family involvement and providing adequate information in the PICU can contribute to quality family-centred care

Regulation of Murine Airway Surface Liquid Volume by CFTR and Ca2+-activated Cl− Conductances

Two Cl− conductances have been described in the apical membrane of both human and murine proximal airway epithelia that are thought to play predominant roles in airway hydration: (1) CFTR, which is cAMP regulated and (2) the Ca2+-activated Cl− conductance (CaCC) whose molecular identity is uncertain. In addition to second messenger regulation, cross talk between these two channels may also exist and, whereas CFTR is absent or defective in cystic fibrosis (CF) airways, CaCC is preserved, and may even be up-regulated. Increased CaCC activity in CF airways is controversial. Hence, we have investigated the effects of CFTR on CaCC activity and have also assessed the relative contributions of these two conductances to airway surface liquid (ASL) height (volume) in murine tracheal epithelia. We find that CaCC is up-regulated in intact murine CF tracheal epithelia, which leads to an increase in UTP-mediated Cl−/volume secretion. This up-regulation is dependent on cell polarity and is lost in nonpolarized epithelia. We find no role for an increased electrical driving force in CaCC up-regulation but do find an increased Ca2+ signal in response to mucosal nucleotides that may contribute to the increased Cl−/volume secretion seen in intact epithelia. CFTR plays a critical role in maintaining ASL height under basal conditions and accordingly, ASL height is reduced in CF epithelia. In contrast, CaCC does not appear to significantly affect basal ASL height, but does appear to be important in regulating ASL height in response to released agonists (e.g., mucosal nucleotides). We conclude that both CaCC and the Ca2+ signal are increased in CF airway epithelia, and that they contribute to acute but not basal regulation of ASL height

Epidemiology and aetiology of community-acquired pneumonia in children: South African Thoracic Society guidelines (part 1)

Background. Pneumonia remains a major cause of morbidity and mortality among South African (SA) children. Improved immunisation regimens, strengthening of HIV programmes, better socioeconomic conditions and new preventive strategies have influenced the epidemiology of pneumonia. Furthermore, sensitive diagnostic tests and better sampling methods in young children improve aetiological diagnosis.Objectives. To summarise current information on childhood community-acquired pneumonia (CAP) epidemiology and aetiology in children as part of the revised South African Thoracic Society guidelines.Methods. The Paediatric Assembly of the South African Thoracic Society and the National Institute for Communicable Diseases expert subgroup on epidemiology and aetiology revised the existing SA guidelines.The subgroup reviewed the published evidence in their area; in the absence of evidence, expert opinion was accepted. Evidence was graded using the British Thoracic Society (BTS) grading system, and the relevant section underwent peer review.Results. Respiratory viruses, particularly respiratory syncytial virus, are the key pathogens associated with hospitalisation for radiologically confirmed pneumonia in HIV-uninfected children. Opportunistic organisms, including Pneumocystis jirovecii, are important pathogens in HIV-infected infants, while non-typable Haemophilus influenzae and Staphylococcus aureus are important in older HIV-infected children. Co-infections with bacteria or other respiratory viruses are common in hospitalised children. Mycobacterium tuberculosis is common in children hospitalised with CAP in SA.Conclusions. Numerous public health measures, including changes in immunisation schedules and expansion of HIV prevention and treatment programmes, have influenced the epidemiology and aetiology of CAP in SA children. These changes have necessitated a revision of the South African Paediatric CAP guidelines, further sections of which will be published as part of a CME series in SAMJ

Diagnosis of community-acquired pneumonia in children: South African Thoracic Society guidelines (part 2)

Background. Accurate diagnosis and attribution of the aetiology of pneumonia are important for measuring the burden of disease, implementing appropriate treatment strategies and developing more effective interventions.Objectives. To produce revised guidelines for the diagnosis of pneumonia in South African (SA) children, encompassing clinical, radiological and aetiological methods.Methods. An expert group was established to review diagnostic evidence and make recommendations for a revised SA guideline. Published evidence was reviewed and graded using the British Thoracic Society grading system.Results. Diagnosis of pneumonia should be considered in a child with acute cough, fast breathing or difficulty breathing. Revised World Health Organization guidelines classify such children into: (i) severe pneumonia; (ii) pneumonia (tachypoea or lower chest indrawing); or (iii) no pneumonia. Malnourished or immunocompromised children with lower chest indrawing should be managed as cases of severe pneumonia. Pulse oximetry should be done, with hospital referral for oxygen saturation <92%. A chest X-ray is indicated in severe pneumonia or when tuberculosis (TB) is suspected. Microbiological investigations are recommended in hospitalised patients or in outbreak settings. Improved aetiological methods show the importance of co-infections. Blood cultures have a low sensitivity (<5%), for diagnosing bacterial pneumonia. Highly sensitive, multiplex tests on upper respiratory samples or sputum detect multiple potential pathogens in most children. However, even in symptomatic children, it may be impossible to distinguish colonising from causative organisms, unless identification of the organism is strongly associated with attribution to causality, e.g. respiratory syncytial virus, Mycobacterium tuberculosis, Bordetella pertussis, influenza, para-influenza or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Investigations for TB should be considered in children with severe pneumonia who have been hospitalised, in a case of a known TB contact, if the tuberculin skin test is positive, if a child is malnourished or has lost weight, and in children living with HIV. Induced sputum may provide a higher yield than upper respiratory sampling for B. pertussis, M. tuberculosis and Pneumocystis jirovecii. Conclusions. Advances in clinical, radiological and aetiological methods have improved the diagnosis of childhood pneumonia