Outcomes of patients with COVID-19 acute respiratory distress syndrome requiring invasive mechanical ventilation admitted to an intensive care unit in South Africa.

BACKGROUND: Up to 32% of patients with COVID-19 pneumonia may require intensive care unit (ICU) admission or mechanical ventilation. Data from low- and middle-income countries on COVID-19 acute respiratory distress syndrome (ARDS) are limited. Groote Schuur Hospital in Cape Town, South Africa, expanded its intensive care service to support patients with COVID-19 ARDS requiring invasive mechanical ventilation (IMV). OBJECTIVES: To report on patients' characteristics and outcomes from the first two pandemic waves. METHODS: All patients with COVID-19 ARDS admitted to the ICU for IMV were included in this prospective cohort study. Data were collected from 5 April 2020 to 5 April 2021. RESULTS: Over the 12-month study period, 461 patients were admitted to the designated COVID-19 ICU. Of these, 380 met the study criteria and 377 had confirmed hospital discharge outcomes. The median (range) age of patients was 51 (17 - 71) years, 50.5% were female, and the median (interquartile range (IQR)) body mass index was 32 (28 - 38) kg/m2. The median (IQR) arterial oxygen partial pressure to fractional inspired oxygen (P/F) ratio was 97 (71 - 128) after IMV was initiated. Comorbidities included diabetes (47.6%), hypertension (46.3%) and HIV infection (10.5%). Of the patients admitted, 30.8% survived to hospital discharge with a median (IQR) ICU length of stay of 19.5 (9 - 36) days. Predictors of mortality after adjusting for confounders were male sex (odds ratio (OR) 1.74), increasing age (OR 1.04) and higher Sequential Organ Failure Assessment (SOFA) score (OR 1.29). CONCLUSIONS: In a resource-limited environment, the provision of IMV support in the ICU achieved 30.8% hospital survival in patients with COVID-19 ARDS. The ability to predict survival remains difficult given this complex disease.

The organisational response of a hospital critical care service to the COVID-19 pandemic: The Groote Schuur Hospital experience.

Background: There are limited data about the coronavirus disease-19 (COVID-19)-related organisational responses and the challenges of expanding a critical care service in a resource-limited setting. Objectives: To describe the ICU organisational response to the pandemic and the main outcomes of the intensive care service of a large state teaching hospital in South Africa. Methods: Data were extracted from administrative records and a prospective patient database with ethical approval. An ICU expansion plan was developed, and resource constraints identified. A triage tool was distributed to referring wards and hospitals. Intensive care was reserved for patients who required invasive mechanical ventilation (IMV). The total number of ICU beds was increased from 25 to 54 at peak periods, with additional non-COVID ICU capacity required during the second wave. The availability of nursing staff was the main factor limiting expansion. A ward-based high flow nasal oxygen (HFNO) service reduced the need for ICU admission of patients who failed conventional oxygen therapy. A team was established to intubate and transfer patients requiring ICU admission but was only available for the first wave. Results: We admitted 461 COVID-19 patients to the ICU over a 13-month period from 5 April 2020 to 5 May 2021 spanning two waves of admissions. The median age was 50 years and duration of ICU stay was 9 days. More than a third of the patients (35%; n=161) survived to hospital discharge. Conclusion: Pre-planning, leadership, teamwork, flexibility and good communication were essential elements for an effective response. A shortage of nurses was the main constraint on ICU expansion. HFNO may have reduced the requirement for ICU admission, but patients intubated after failing HFNO had a poor prognosis. Contributions of the study: We describe the organisational requirements to successfully expand critical care facilities and strategies to reduce the need for invasive mechanical ventilation in COVID-19 pneumonia. We also present the intensive care outcomes of these patients in a resource-constrained environment.

Comparison of same day versus delayed enumeration of TB-specific T cell responses.

BACKGROUND/OBJECTIVE: Flexibility in sample processing may improve test utility of the quantitative antigen-specific T cell assay (T-SPOT.TB). We investigated whether delayed sample processing with and without the use of T-Cell Xtend, a proprietary reagent, impacted upon test accuracy. METHODS: Blood samples obtained from 363 sequentially recruited tuberculosis suspects or treated patients were processed immediately (day 0) and at different times after receipt of the sample [approximately 24-h (day 1) or approximately 32-h (day 2)] with and without adding T-Cell Xtend. RESULTS: T-Cell-Xtend-independent median ELISPOT counts (spot forming cells per million peripheral blood mononuclear cells) were significantly higher at day 1 versus day 0 (114 vs. 100; n=66; p=0.03); inter-time-point agreement between the results was 95.45% and the conversion/reversion rate was 4.55%. By contrast, counts on day 0 without T-Cell Xtend versus day 1 with T-Cell Xtend were similar (56 vs. 56; n=215), inter-time-point agreement between the results was 97.17%, and the conversion/reversion rate was 2.83%. Counts performed at day 2 with T-Cell Xtend were not significantly different from day 0. These findings were independent of HIV status. CONCLUSION: There was high agreement between results when samples were processed immediately and after a 24-h delay. However, although the use of T-Cell Xtend appeared to reduce the number of conversions/reversions this reduction was not statistically significant. Larger studies are required to clarify these findings.

Utility of quantitative T-cell responses versus unstimulated interferon-{gamma} for the diagnosis of pleural tuberculosis.

The clinical utility of antigen-specific interferon (IFN)-gamma release assays (IGRAs) using pleural mononuclear cells, for the diagnosis of tuberculosis (TB), requires clarification. We compared the diagnostic utility of unstimulated pleural IFN-gamma levels with several pleural antigen-specific T-cell IGRAs (early secretory antigenic target-6 and culture filtrate protein-10 (T-SPOT.(R)TB, QuantiFERON(R)-TB Gold In-tube), purified protein derivative (PPD) and heparin-binding haemagglutinin (HBHA)) in 78 South African TB suspects. Test results were compared against a clinical score and a reference standard. Out of 74 evaluable subjects 48, seven and 19 had definite, probable and no TB, respectively. 11 (15%) out of 74 pleural samples (nine (19%) out of 48 of the definite TB cases) had total cell counts that were inadequate for T-cell processing. In the remaining 63 samples, the sensitivity, specificity, positive predictive value and negative predictive value of different diagnostic methods were as follows. Maximal bioclinical score: 54, 89, 92 and 43%, respectively; T-SPOT.(R)TB: 86, 60, 84 and 64%, respectively; QuantiFERON(R)-TB Gold In-tube: 57, 80, 87 and 44%, respectively; HBHA-specific IGRA: 59, 31, 64 and 27%, respectively; PPD-specific IGRA: 81, 40, 76 and 46%, respectively; and pleural fluid unstimulated IFN-gamma: 97, 100, 100 and 94%, respectively. Unstimulated IFN-gamma was the most accurate test for distinguishing TB from non-TB effusions in a high-burden setting. The antigen-specific T-cell IGRAs were limited by suboptimal accuracy and the inability to isolate sufficient mononuclear cells to perform the assay.

Exposure of cord blood to Mycobacterium bovis BCG induces an innate response but not a T-cell cytokine response.

Despite routine vaccination with Mycobacterium bovis bacillus Calmette-Guérin (BCG) soon after birth, tuberculosis in babies and adults remains epidemic in South Africa. The immune responses of the naïve newborn child and how they are affected by vaccination with BCG are as yet not fully understood. Immunity during pregnancy and in healthy human newborns may be skewed toward type 2 cytokine production; however, it is type 1 cytokines that are required for protection against M. tuberculosis infection. To better understand neonatal cytokine responses prior to and following exposure to mycobacteria, we have collected cord blood and peripheral blood samples and evaluated the cytokine response following ex vivo incubation with BCG. Gamma interferon (IFN-gamma), interleukin 10 (IL-10), IL-12, and low levels of IL-13 and IL-5 but no IL-4 were secreted into the culture supernatant of cord blood mononuclear cells. Intracellular staining showed that IL-10 and IL-12 were produced by monocytes and that IFN-gamma was produced by natural killer (NK) cells but not by CD4(+) or CD8(+) T cells. In contrast, in the peripheral blood samples collected from babies 13 weeks post-BCG vaccination, IFN-gamma was detected within CD4(+) and CD8(+) cells. Taken together, the data suggest a central role for Th1 cytokines in naïve as well as BCG-vaccinated neonates in the protective immune response to tuberculosis. NK cell-derived IFN-gamma produced in naïve neonates likely plays a key protective role via monocyte activation and the priming of a subsequent adaptive Th1 response.

The role of neurosurgery in the treatment of cerebral metastases from choriocarcinoma: a report of two cases.

Cerebral metastases from choriocarcinoma are a poor prognostic indicator of outcome in both the World Health Organization and FIGO classification systems. However, with the increased experience with chemotherapy and radiotherapy the prognosis of this group of patients has improved substantially. Neurosurgery remains an option for selected patients. We present two patients who underwent craniotomy as part of their management of choriocarcinoma, and review the role of neurosurgery in the treatment of gestational trophoblastic disease.

Intradural cervical lipomas with intracranial extension: a management strategy based on a case report and review of the literature.

Intradural cervical lipomas with intracranial extension are very rare. There have been 12 previously reported cases. We report an 18-year-old female who presented with quadraparesis and incontinence, and review the previously published literature. Intradural lipomas with intracranial extension occur in younger patients when compared with those without intracranial extension. Roughly half of high cervical lipomas have intracranial extension. This results in a more complicated course of surgical management and a worse prognosis. While the relatively older patients most commonly present with quadriplegia, in younger patients there may be a more variable presentation. Almost half the patients had symptoms ascribable to the intracranial component. In all patients, no more than subtotal resection and decompression was achieved using duroplasty if necessary. Only five patients showed functional recovery. We propose a management strategy for this condition.

Craniocerebral gunshot injuries in South Africa--a suggested management strategy.

OBJECTIVE: To determine the outcome of craniocerebral gunshot injuries, analyse factors that affect prognosis and suggest a management protocol. DESIGN: A retrospective analysis of civilian craniocerebral gunshot injuries treated over a 7-year period. SETTING: Groote Schuur Hospital's neurosurgery and trauma unit service. PATIENTS: One hundred and eighty-one patients with craniocerebral gunshot injuries were admitted to the Department of Neurosurgery, Groote Schuur Hospital, University of Cape Town, over a 7-year period and a retrospective analysis of these patient records with regard to outcome and prognostic factors was carried out. RESULTS: Seventy-six patients sustained non-penetrating injuries, 8 (11%) of whom had underlying cerebral injury on computed tomography (CT) scan. The prognosis was good in the case of non-penetrating injuries. One hundred and five patients sustained penetrating injuries and 57% (62) had a poor outcome. A Glasgow Coma Score (GCS) of 5 or less following resuscitation was associated with a 98% mortality rate. CT scan evidence of transventricular injury was associated with 100% mortality, bihemispheric injury with 90% mortality, and diffuse cerebral swelling with 81% mortality. CONCLUSION: Patients with non-penetrating craniocerebral gunshot injuries should all undergo a CT scan as 10% will have cerebral injury. The prognosis is normally good. In penetrating craniocerebral gunshot injuries a GCS of 5 or less, or a GCS of 8 or less with CT scan findings of transventricular or bihemispheric injury have such a poor outcome that conservative treatment is indicated.

Transsphenoidal surgery for Cushing's disease: outcome in patients with a normal magnetic resonance imaging scan.

OBJECTIVE: Transsphenoidal surgery for Cushing's disease from a pituitary adenoma is an effective and safe treatment. Definitive preoperative diagnosis of Cushing's disease caused by a pituitary adenoma is often difficult, particularly in patients with normal imaging studies and a normal sella turcica. We present the outcome of transsphenoidal surgery in patients with presumed Cushing's disease and a normal pituitary magnetic resonance imaging scan. METHODS: Between January 1992 and December 1997, 105 patients underwent transsphenoidal surgery for Cushing's disease at our institution. The criteria for inclusion in this study were clinical and biochemical studies strongly suggestive of Cushing's disease, a normal magnetic resonance imaging scan with normal sella and sellar contents, no previous pituitary surgery, and transsphenoidal surgery performed at this institution. Eighteen patients fulfilled these criteria, and their results were analyzed retrospectively. RESULTS: The average age of the patients was 47.8 years; there were 13 women and 5 men. Inferior petrosal sinus sampling with and without corticotropin-releasing hormone stimulation was performed in 16 patients with correct localization of the lesion in 13 (81%). During surgery, the surgeon identified and removed 17 pituitary tumors; 15 patients had selective adenomectomies, one had a hemihypophysectomy, and two had total hypophysectomies. Thirteen discrete adrenocorticotropic hormone-secreting adenomas were proven histologically, and one pituitary gland had diffuse involvement with tumor. Complications occurred in five patients. Sixteen patients who were followed up for an average of 21.6 months had sustained remission, 12 of whom were profoundly hypocortisolemic immediately after surgery. CONCLUSION: In patients with Cushing's disease and a normal magnetic resonance imaging scan, an experienced surgeon can perform transsphenoidal surgery resulting in effective removal of very small microadenomas, with clinical and biochemical remission in the majority. Inferior petrosal sinus sampling is helpful in localizing the adenoma.

Complications in a contemporary series of patients who underwent transsphenoidal surgery for Cushing's disease.

OBJECT: Transsphenoidal surgery is the usual treatment of choice for adrenocorticotropic hormone-secreting pituitary adenomas associated with Cushing's disease. In this paper the authors investigate the complications of transsphenoidal surgery in the treatment of a contemporary series of patients with Cushing's disease. METHODS: Between January 1992 and December 1997, 105 patients with Cushing's disease underwent transsphenoidal surgery at the University of Virginia Health Sciences Center. A retrospective analysis of the complications was conducted, and the mortality rate was found to be 0.9% and permanent morbidity was 1.8%. The overall number of complications was 14 (13.3%), which included seven complications directly related to surgery; one instance of permanent diabetes insipidus; one syndrome of inappropriate secretion of antidiuretic hormone; and five medical complications (four patients developed deep vein thrombosis and one developed pneumonia). CONCLUSIONS: Transsphenoidal surgery for Cushing's disease has a higher complication rate than that for pituitary adenomas in general. This is primarily related to a greater number of medical complications, most notably deep vein thrombosis, resulting from the generally debilitated state of most patients with Cushing's disease. In view of the high incidence of deep vein thrombosis in these patients, prophylaxis for thromboembolism during the perioperative period is recommended.

Severe head injury in children--a preventable but forgotten epidemic.

OBJECTIVE: To determine the outcome of seriously head-injured children and to analyse the factors that affect their prognosis. DESIGN: A retrospective analysis of all severely head-injured children treated between 1990 and 1993. SETTING: Red Cross War Memorial Children's Hospital's trauma unit and neurosurgery service. PATIENTS: One hundred and two children under the age of 14 years with admission Glasgow Coma Scores (GCSs) of below 8. RESULTS: There were 57 boys and 45 girls. The average time of assessment after injury was 2.8 hours. Eighty-three injuries were caused by pedestrian motor vehicle accidents. Thirty-seven were associated with other serious organ system injuries. Fifty-eight children died and only 36 made a good recovery. All children with a GCS of 3-4 died. Factors that were particularly associated with a poor prognosis were: (i) age less than 3 years; (ii) associated extracranial injury; (iii) GCS 3-4 following resuscitation; and (iv) diffuse cerebral swelling on computed tomography. CONCLUSION: Pedestrian motor vehicle accidents are the most common cause of serious paediatric head injury in the Cape Town area. Children with a presenting coma score of less than 8 have an extremely high mortality and morbidity rate, despite modern intensive care. Preventive strategies are essential.

Investigation and management of blunt renal injuries in children: a review of 11 years' experience.

Over an 11-year period, 333 patients aged 6 months to 13 years were investigated for suspected blunt renal trauma. Ninety-one renal injuries were demonstrated. All patients who had preexisting pathology sustained major (ie, grade III or IV) injuries and all those who required surgery presented with 4+ or macroscopic hematuria with or without loin signs. Intravenous pyelography (IVP) showed no injury in 140 (89%) of 157 patients who had 0 to 3+ microscopic hematuria, and did not influence management in the remaining 17 patients. Seventy-eight (84%) patients were treated nonoperatively, with one death and few complications. Thirteen (14%) patients underwent early laparotomy, with a nephrectomy rate of 92%. No patient with a renal pedicle injury was considered suitable for vascular reconstruction. We conclude that (1) contrast studies are of little value in pediatric patients with asymptomatic microscopic hematuria after blunt trauma; (2) IVP remains the most cost-effective means of investigating renal injuries; and (3) laparotomy is only indicated for ongoing hemorrhage from the severely injured kidney and in a few selected patients with renal pedicle injuries.