Novel Map Biopsy Technique to Define the Extent of Infection Before Penetrating Keratoplasty for Acanthamoeba Keratitis.

PURPOSE: The purpose of this study was to report a novel approach of prepenetrating keratoplasty (PKP) corneal map biopsies to define the extent of Acanthamoeba cyst infiltration in recalcitrant Acanthamoeba keratitis. METHODS: Corneal map biopsies were performed 1 week before PKP. Four biopsies, 1 from each peripheral corneal quadrant, were obtained to delineate the extent of microscopic infection. Histological results of these map biopsies were used to determine the size and location of the subsequent PKP. RESULTS: In our first case, map biopsies revealed Acanthamoeba cysts in 2 of the 4 biopsies. This led to an inferotemporally eccentric 8.5-mm PKP. The final histology report indicated that the closest resection margin was 0.08 mm. In our second case, the peripheral map biopsies were clear and an inferiorly eccentric 8.25-mm PKP was performed. The final histology report indicated that the closest resection margin was 2.3 mm. Both grafts have remained clear at 6 months postoperatively. CONCLUSIONS: Map biopsies of the cornea can achieve total removal of the corneal tissues infested with Acanthamoeba cysts and prevent reinfection of the donor graft.

Post-enucleation outcomes of patients with uveal melanoma in Scotland.

BACKGROUND/OBJECTIVES: To investigate post-enucleation outcomes and assess the effect of extrascleral extension (ESE) on these outcomes for patients with uveal melanoma (UM) managed at a tertiary referral centre in Scotland. SUBJECTS/METHODS: Retrospective review of all cases of UM managed by the Scottish Ocular Oncology Service for which enucleation was undertaken between 13/03/2008 and 31/12/2020. Primary outcomes were length of survival, time-to-metastasis (TTM) and local recurrence rate. Secondary outcomes were the effects of the presence of ESE, ESE size, and the use of adjuvant external beam radiotherapy (EBRT) on the primary outcomes. RESULTS: Of 172 enucleated UMs, 32 (18.6%) had ESE. Over a median follow-up period of 33.7 months (range = 1.1-163.7 months), 91 (52.9%) patients died. The median length of all-cause survival of 54.1 months (range = 1.1-163.7 months). One-year, 5-year, and 10-year survival rates were 84.8%, 49.1%, and 30.9%, respectively. Eighty-four (49.7%) patients had metastatic disease. The median TTM of 42.2 months (range = 0.4-106.8 months). Proportions of patients who developed metastases within 1-year, 5-years and 10-years post-enucleation were 22.7%, 52.8%, and 71.8%, respectively. There was one instance of local orbital recurrence. ESE was associated with a significantly shorter length of survival (p = 0.03). There was a trend towards a shorter length of survival and TTM with ESE > 5 mm and those who received adjuvant EBRT. CONCLUSIONS: ESE was present in one-sixth of our cohort and was associated with a significantly shorter length of survival, particularly in the presence of ESE > 5 mm or high-risk characteristics warranting adjuvant EBRT. This data will aid prognostication of the patients in our service.

The efficacy and safety of prophylactic corticosteroids for the prevention of adverse outcomes in patients undergoing heart surgery using cardiopulmonary bypass: a systematic review and meta-analysis of randomized controlled trials.

Corticosteroids are often administered prophylactically to attenuate the inflammatory response associated with cardiac surgery using cardiopulmonary bypass (CPB). However, the efficacy and safety profile of corticosteroids remain uncertain. The primary aim of this systematic review and meta-analysis was to investigate the effect of corticosteroids on mortality in adult cardiac surgery using CPB. Secondary aims were to examine the effect of corticosteroids on myocardial adverse events, pulmonary adverse events, atrial fibrillation, surgical site infection, gastrointestinal bleeding and duration of stay in the intensive care unit and hospital. Randomized controlled trials (RCTs) were systematically searched in electronic databases (MEDLINE, EMBASE, CINAHL, CENTRAL and Web of Science) from their inception until March 2019. Observational studies, case reports, case series and literature reviews were excluded. Sixty-two studies (n = 16 457 patients) were included in this meta-analysis. There was no significant difference in mortality between the corticosteroid and placebo groups [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.81-1.14; P = 0.65, participants = 14 693, studies = 24, evidence of certainty: moderate]. Compared to those receiving a placebo, patients who were given corticosteroids had a significantly higher incidence of myocardial adverse events (OR 1.17, 95% CI 1.03-1.33; P = 0.01, participants = 14 512, studies = 23) and a lower incidence of pulmonary adverse events (OR 0.86, 95% CI 0.75-0.98; P = 0.02, participants = 13 426, studies = 17). The incidences of atrial fibrillation (OR 0.87, 95% CI 0.81-0.94; P < 0.001, participants = 14 148, studies = 24) and surgical site infection (OR 0.81, 95% CI 0.73-0.90; P < 0.001, participants = 13 946; studies = 22) were all lower in patients who were given corticosteroids. In the present meta-analysis of 62 RCTs (16 457 patients), including the 2 major RCTs (SIRS and DECS trials: 12 001 patients), we found that prophylactic corticosteroids in cardiac surgery did not reduce mortality. The clinical significance of an increase in myocardial adverse events remains unclear as the definition of a relevant myocardial end point following cardiac surgery varied greatly between RCTs.

The effect of ketamine on emergence agitation in children: A systematic review and meta-analysis.

BACKGROUND: Ketamine is believed to reduce the incidence of emergence agitation in children undergoing surgery or procedure. However, recent randomized controlled trials reported conflicting findings. AIMS: To investigate the effect of ketamine on emergence agitation in children. METHODS: Databases of MEDLINE, EMBASE, and CENTRAL were systematically searched from their start date until February 2019. Randomized controlled trials comparing intravenous ketamine and placebo in children were sought. The primary outcome was the incidence of emergence agitation. Secondary outcomes included postoperative pain score, duration of discharge time, and the adverse effects associated with the use of ketamine, namely postoperative nausea and vomiting, desaturation, and laryngospasm. RESULTS: Thirteen studies (1125 patients) were included in the quantitative meta-analysis. The incidence of emergence agitation was 14.7% in the ketamine group and 33.3% in the placebo group. Children receiving ketamine had a lower incidence of emergence agitation, with an odds ratio being 0.23 (95% confidence interval: 0.11 to 0.46), certainty of evidence: low. In comparison with the placebo, ketamine group achieved a lower postoperative pain score (odds ratio: -2.42, 95% confidence interval: -4.23 to -0.62, certainty of evidence: very low) and lower pediatric anesthesia emergence delirium scale at 5 minutes after operation (odds ratio: -3.99, 95% confidence interval: -5.03 to -2.95; certainty of evidence: moderate). However, no evidence was observed in terms of incidence of postoperative nausea and vomiting, desaturation, and laryngospasm. CONCLUSION: In this meta-analysis of 13 randomized controlled trials, high degree of heterogeneity and low certainty of evidence limit the recommendations of ketamine for the prevention of emergence agitation in children undergoing surgery or imaging procedures. However, the use of ketamine is well-tolerated without any notable adverse effects across all the included trials. PROSPERO REGISTRATION: CRD42019131865.

Surgical versus nonsurgical management for type II odontoid fractures in the elderly population: a systematic review.

BACKGROUND: Odontoid process fractures, of which type II constitute the majority, are an increasingly important cause of morbidity and mortality in the elderly population. The incidence of geriatric type II fractures is steadily increasing in line with the aging population. However, the decision between surgical and non-surgical intervention for type II fractures in the elderly remains controversial. PURPOSE: The present study aims to synthesize the current published literature comparing outcomes following surgical and non-surgical interventions for type II odontoid fractures in the elderly population (≥65 years old). STUDY DESIGN/SETTING: Systematic review and meta-analysis were performed. METHODS: A systematic search of MEDLINE, MEDLINE In-Progress & Other Non-Indexed Citations, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) was performed to identify available evidence in English language. Studies with extractable data for all type II odontoid fractures in participants aged 65 years or older and which compared surgical and non-surgical intervention were included. Methodological quality was assessed using the Downs & Black checklist. Primary outcomes were mortality at short-term follow-up (≤3 months), mortality at long-term follow-up (predetermined study endpoint or mean follow-up length), and radiological union rate. Funding was provided by The University of Edinburgh for travel expenses to present this paper at the Society of British Neurological Sciences 2016 Conference ($170). RESULTS: Twelve studies (n=1,098), all non-randomized, met eligibility criteria. Methodological quality was particularly poor in the confounding, bias, and power domains of assessment. Substantial methodological and statistical heterogeneity allowed only a narrative synthesis of the primary outcomes. Overall, data on mortality at short-term follow-up appeared to favor neither surgical nor non-surgical intervention. A small favorable outcome in surgically managed patients over non-surgically managed patients in terms of mortality at long-term follow-up was not proven conclusive because of considerable heterogeneity in study methodologies. Inadequate reporting of the time point of union assessment introduced the potential for significant intra- and interstudy heterogeneity and precluded assessment of union rates. CONCLUSIONS: Evidence on this controversial topic is sparse, markedly heterogeneous, and of poor quality. Well-designed prospective trials adhering to guidance published by the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative are required to inform clinical practice on this contentious but growing issue. Future randomized controlled trials should include an assessment of frailty and medical comorbidities with suitable patients subsequently randomized to surgical or non-surgical treatment.

Psychiatric symptomatology after delirium: a systematic review.

Delirium is an acute and usually transient severe neuropsychiatric syndrome associated with significant long-term physical morbidity. However, its chronic psychiatric sequelae remain poorly characterized. To investigate the prevalence of psychiatric symptoms, namely anxiety, depressive, and post-traumatic stress disorder (PTSD) symptoms after delirium, a systematic literature search of MEDLINE, EMBASE and PsycINFO databases was performed independently by two authors in March 2016. Bibliographies were hand-searched, and a forward- and backward-citation search using Web of Science was performed for all included studies. Of 6411 titles, we included eight prospective cohort studies, including 370 patients with delirium and 1073 without delirium. Studies were heterogeneous and mostly included older people from a range of clinical groups. Consideration of confounders was variable. The prevalence of depressive symptoms was almost three times higher in patients with delirium than in patients without delirium (22.2% vs 8.0%, risk ratio = 2.79; 95% confidence interval = 1.36-5.73). There was no statistically significant difference between the prevalence of anxiety symptoms between patients with and without delirium. The prevalence of PTSD symptoms after delirium was inconclusive: only one study investigated this and no association between PTSD symptoms after delirium was reported. There is limited published evidence of the prevalence of psychiatric symptoms after non-ICU delirium and the strongest evidence is for depressive symptoms. Further longitudinal studies are warranted to investigate the prevalence of anxiety and PTSD symptoms.

The prion protein protease sensitivity, stability and seeding activity in variably protease sensitive prionopathy brain tissue suggests molecular overlaps with sporadic Creutzfeldt-Jakob disease.

INTRODUCTION: Variably protease sensitive prionopathy (VPSPr) is a recently described, sporadic human prion disease that is pathologically and biochemically distinct from the currently recognised sporadic Creutzfeldt-Jakob disease (sCJD) subtypes. The defining biochemical features of the abnormal form of the prion protein (PrPSc) in VPSPr are increased sensitivity to proteolysis and the presence of an N- and C-terminally cleaved ~8 kDa protease resistant PrPSc (PrPres) fragment. The biochemical and neuropathological profile of VPSPr has been proposed to resemble either Gerstmann-Sträussler-Scheinker syndrome (GSS) or familial CJD with the PRNP-V180I mutation. However, in some cases of VPSPr two protease resistant bands have been observed in Western blots that co-migrate with those of type 2 PrPres, suggesting that a proportion of the PrPSc present in VPSPr has properties similar to those of sCJD. RESULTS: Here, we have used conformation dependent immunoassay to confirm the presence of PrPSc in VPSPr that is more protease sensitive compared with sCJD. However, CDI also shows that a proportion of PrPSc in VPSPr resists PK digestion of its C-terminus, distinguishing it from GSS associated with ~8 kDa PrPres, and showing similarity to sCJD. Intensive investigation of a single VPSPr case with frozen tissue from multiple brain regions shows a broad, region-specific spectrum of protease sensitivity and differential stability of PrPSc in the absence of PK treatment. Finally, using protein misfolding cyclic amplification and real-time quaking induced conversion, we show that VPSPr PrPSc has the potential to seed conversion in vitro and that seeding activity is dispersed through a broad range of aggregate sizes. We further propose that seeding activity is associated with the ~19 and ~23 kDa PrPres rather than the ~8 kDa fragment. CONCLUSIONS: Therefore, PrPSc in VPSPr is heterogeneous in terms of protease sensitivity and stability to denaturation with the chaotrope GdnHCl and includes a proportion with similar properties to that found in sCJD.