Keyhole Approaches Applied to Clipping of Acutely Ruptured Intracerebral Aneurysms-A Technical Note and Case Series.

BACKGROUND: Evolution of keyhole techniques in aneurysm surgery allows for definitive surgical management of aneurysmal pathology with little disruption of normal surrounding tissue. While experienced vascular neurosurgeons are increasingly applying keyhole techniques to unruptured aneurysms, experience with ruptured aneurysms is limited. OBJECTIVE: We sought to explore technical nuances and present operative outcomes for our series of 40 consecutive patients presenting with ruptured intracerebral aneurysms treated with surgical clipping via a keyhole approach. METHODS: This study is a consecutive, single-surgeon, single-center retrospective case series of aneurysms clipped with keyhole approaches at Helen Joseph Hospital in Johannesburg, South Africa. Patients presenting with subarachnoid hemorrhage were worked up exclusively with computed tomography. On the basis of vessel location and unique anatomic features, aneurysms were clipped through one of these approaches: minipterional, supraorbital, or keyhole interhemispheric. Operative details were assessed on retrospective file review, and patient outcomes were assessed on clinic follow-up. RESULTS: A minipterional approach was used for 55% of cases, the supraorbital approach in 30% of cases, and the mini-interhemispheric approach in 15% of cases. The intraoperative aneurysm rupture rate was 26.2%. Complete aneurysm occlusion was achieved in 97.4% with none of the 40 cases requiring conversion of a keyhole to a larger craniotomy. A good outcome was achieved for 72.5% of patients (modified Rankin Scale score ≤2). For patients presenting with World Federation of Neurological Surgeons grade I to III subarachnoid hemorrhage, 92.9% achieved a good outcome. CONCLUSIONS: The present series supports the concept that sound technical execution of keyhole approaches, even in the setting of acutely ruptured cerebral aneurysms, is a viable option for clipping of intracranial aneurysms.

Anti-C5a antibody (vilobelimab) therapy for critically ill, invasively mechanically ventilated patients with COVID-19 (PANAMO): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial.

BACKGROUND: Vilobelimab, an anti-C5a monoclonal antibody, was shown to be safe in a phase 2 trial of invasively mechanically ventilated patients with COVID-19. Here, we aimed to determine whether vilobelimab in addition to standard of care improves survival outcomes in this patient population. METHODS: This randomised, double-blind, placebo-controlled, multicentre phase 3 trial was performed at 46 hospitals in the Netherlands, Germany, France, Belgium, Russia, Brazil, Peru, Mexico, and South Africa. Participants aged 18 years or older who were receiving invasive mechanical ventilation, but not more than 48 h after intubation at time of first infusion, had a PaO2/FiO2 ratio of 60-200 mm Hg, and a confirmed SARS-CoV-2 infection with any variant in the past 14 days were eligible for this study. Eligible patients were randomly assigned (1:1) to receive standard of care and vilobelimab at a dose of 800 mg intravenously for a maximum of six doses (days 1, 2, 4, 8, 15, and 22) or standard of care and a matching placebo using permuted block randomisation. Treatment was not continued after hospital discharge. Participants, caregivers, and assessors were masked to group assignment. The primary outcome was defined as all-cause mortality at 28 days in the full analysis set (defined as all randomly assigned participants regardless of whether a patient started treatment, excluding patients randomly assigned in error) and measured using Kaplan-Meier analysis. Safety analyses included all patients who had received at least one infusion of either vilobelimab or placebo. This study is registered with ClinicalTrials.gov, NCT04333420. FINDINGS: From Oct 1, 2020, to Oct 4, 2021, we included 368 patients in the ITT analysis (full analysis set; 177 in the vilobelimab group and 191 in the placebo group). One patient in the vilobelimab group was excluded from the primary analysis due to random assignment in error without treatment. At least one dose of study treatment was given to 364 (99%) patients (safety analysis set). 54 patients (31%) of 177 in the vilobelimab group and 77 patients (40%) of 191 in the placebo group died in the first 28 days. The all-cause mortality rate at 28 days was 32% (95% CI 25-39) in the vilobelimab group and 42% (35-49) in the placebo group (hazard ratio 0·73, 95% CI 0·50-1·06; p=0·094). In the predefined analysis without site-stratification, vilobelimab significantly reduced all-cause mortality at 28 days (HR 0·67, 95% CI 0·48-0·96; p=0·027). The most common TEAEs were acute kidney injury (35 [20%] of 175 in the vilobelimab group vs 40 [21%] of 189 in the placebo), pneumonia (38 [22%] vs 26 [14%]), and septic shock (24 [14%] vs 31 [16%]). Serious treatment-emergent adverse events were reported in 103 (59%) of 175 patients in the vilobelimab group versus 120 (63%) of 189 in the placebo group. INTERPRETATION: In addition to standard of care, vilobelimab improves survival of invasive mechanically ventilated patients with COVID-19 and leads to a significant decrease in mortality. Vilobelimab could be considered as an additional therapy for patients in this setting and further research is needed on the role of vilobelimab and C5a in other acute respiratory distress syndrome-causing viral infections. FUNDING: InflaRx and the German Federal Government.

Adherence to SATS antibiotic recommendations in patients with community acquired pneumonia in Johannesburg, South Africa.

INTRODUCTION: Antibiotic guidelines have been published by various societies indicating the optimal empiric antibiotic treatment of patients with community acquired pneumonia (CAP); however, no studies have been undertaken in South Africa investigating whether the most recent South African Thoracic Society (SATS) antibiotic CAP guideline, published in 2007, is being adhered to, or whether adherence is associated with improved patient outcomes. METHODOLOGY: This was a retrospective record review over a one-year period undertaken to document levels of adherence to the 2007 SATS guideline for CAP management in adults at an academic teaching hospital. RESULTS: A total of 181 patients with CAP were included in the study, of whom 101 were female, and 109 were known to be HIV-seropositive. The majority (66%) of the patients received antibiotic treatment that was guideline-adherent. In those patients who received treatment that was non-adherent to the guideline recommendations, rather than receiving inadequate cover, they actually had received treatment that was in excess of what was recommended.  There was no significant difference in the length of hospital stay among the two patient groups; however, a significantly longer time to clinical stability was found in patients who had received guideline-adherent treatment. Only one CAP patient died and therefore it was not possible to determine the impact of guideline adherence on patient mortality. CONCLUSION: Results of this study indicated a relatively high level of SATS guideline adherence. Guideline adherence was not associated with improved patient outcomes.

Determining need for hospitalisation: Evaluation of the utility of the CRB-65 score in patients with community-acquired pneumonia presenting to an emergency department.

BACKGROUND: The CRB-65 severity of illness score, used for assessing patients with community-acquired pneumonia (CAP), may be of particular benefit in resource-constrained areas, since it relies purely on clinical parameters. OBJECTIVE: To assess the potential accuracy of the CRB-65 score when used in deciding whether to hospitalise patients with CAP presenting to an emergency department (ED). METHODS: Prospective, observational study in an academic hospital in Johannesburg, South Africa. Data from adult patients with radiologically confirmed CAP were analysed. RESULTS: Overall, 152 patients were enrolled (79 females, 73 males; median age 36.5 years). Several diverse criteria had been used by the ED doctors in admission decisions, while the CRB-65 score had been used in only 3/152 patients (1.6%). Overall, 68/152 patients (44.7%) had been managed as inpatients and 84/152 (55.3%) as outpatients. If the CRB-65 had been used as the sole criterion for site-of-care decisions, 107/152 patients (70.4%) would potentially have been managed as outpatients and 45/152 (29.6%) as inpatients. Achieving a stable clinical condition took longer (p=0.037) and mortality was higher (p<0.001) in patients with higher than lower CRB-65 scores. All five patients who died were inpatients. Of these, three (60.0%) would have been classified by the CRB-65 as having an intermediate mortality risk and two (40.0%) as having a high mortality risk. CONCLUSIONS: This study demonstrates the utility of the CRB-65 score in accurately determining the need for admission of patients with CAP presenting to an ED in a resource-constrained environment.