Development of the SAFETEA Scores for Predicting Risks of Complications of Preventive Endovascular or Microneurosurgical Intracranial Aneurysm Occlusion.

OBJECTIVE: Preventive unruptured intracranial aneurysm occlusion can reduce the risk of subarachnoid hemorrhage, but both endovascular and microneurosurgical treatment carry a risk of serious complications. To improve individualized management decisions, we developed risk scores for complications of endovascular and microneurosurgical treatment based on easily retrievable patient, aneurysm, and treatment characteristics. METHODS: For this multicenter cohort study, we combined individual patient data from unruptured intracranial aneurysm patients ≥18 years undergoing preventive endovascular treatment (standard, balloon-assisted or stent-assisted coiling, Woven EndoBridge-device, or flow-diverting stent) or microneurosurgical clipping at one of 10 participating centers from three continents between 2000-2018. The primary outcome was death from any cause or clinical deterioration from neurological complications ≤30 days. We selected predictors based on previous knowledge about relevant risk factors and predictor performance and studied the association between predictors and complications with logistic regression. We assessed model performance with calibration plots and concordance (c) statistics. RESULTS: Of 1282 included patients, 94 (7.3%) had neurological symptoms that resolved <30 days, 140 (10.9%) had persisting neurological symptoms, and 6 died (0.5%)). At 30 days, 52 patients (4.1%) were dead or dependent. Predictors of procedural complications were: size of aneurysm, aneurysm location, familial subarachnoid hemorrhage, earlier atherosclerotic disease, treatment volume, endovascular modality (for endovascular treatment) or extra aneurysm configuration factors (for microneurosurgical treatment; branching artery from aneurysm neck or unfavorable dome-to-neck ratio), and age (acronym: SAFETEA). For endovascular treatment (n=752), the c-statistic was 0.72 (95%CI:0.67-0.77) and the absolute complication risk ranged from 3.2% (95%CI:1.6%-14.9%;≤1 point) to 33.1% (95%CI:25.4%-41.5%;≥6 points). For microneurosurgical treatment (n=530), the c-statistic was 0.72 (95%CI:0.67-0.77) and the complication risk ranged from 4.9% (95%CI:1.5%-14.9%;≤1 point) to 49.9% (95%CI:39.4%-60.6%;≥6 points). CONCLUSIONS: The SAFETEA risk scores for endovascular and microneurosurgical treatment are based on seven easily retrievable risk factors to predict the absolute risk of procedural complications in patients with unruptured intracranial aneurysms. The scores need external validation before the predicted risks can be properly used to support decision making in clinical practice.

cDC2 and plasmacytoid dendritic cells diminish from tissues of patients with non-Hodgkin orbital lymphoma and idiopathic orbital inflammation.

Non-Hodgkin orbital lymphoma (NHOL) and idiopathic orbital inflammation (IOI) are common orbital conditions with largely unknown pathophysiology. To investigate the immune cell composition of these diseases, we performed standardized 29 parameter flow cytometry phenotyping in peripheral blood mononuclear cells of 18 NHOL patients, 21 IOI patients, and 41 unaffected controls. Automatic gating by FlowSOM revealed decreased abundance of meta-clusters containing dendritic cells in patients, which we confirmed by manual gating. A decreased percentage of (HLA-DR+ CD303+ CD123+ ) plasmacytoid dendritic cells (pDC) in the circulation of IOI patients and decreased (HLA-DR+ CD11c+ CD1c+ ) conventional dendritic cells (cDC) type-2 for IOI patients were replicated in an independent cohort of patients and controls. Meta-analysis of both cohorts demonstrated that pDCs are also decreased in blood of NHOL patients and highlighted that the decrease in blood cDC type-2 was specific for IOI patients compared to NHOL or controls. Deconvolution-based estimation of immune cells in transcriptomic data of 48 orbital biopsies revealed a decrease in the abundance of pDC and cDC populations within the orbital microenvironment of IOI patients. Collectively, these data suggest a previously underappreciated role for dendritic cells in orbital disorders.

A pan-inflammatory microRNA-cluster is associated with orbital non-Hodgkin lymphoma and idiopathic orbital inflammation.

Non-Hodgkin orbital lymphoma (NHOL) and idiopathic orbital inflammation (IOI) are common orbital conditions with largely unknown pathophysiology that can be difficult to diagnose. In this study we aim to identify serum miRNAs associated with NHOL and IOI. We performed OpenArray® miRNA profiling in 33 patients and controls. Differentially expressed miRNAs were technically validated across technology platforms and replicated in an additional cohort of 32 patients and controls. We identified and independently validated a serum miRNA profile of NHOL that was remarkably similar to IOI and characterized by an increased expression of a cluster of eight miRNAs. Pathway enrichment analysis indicated that the miRNA-cluster is associated with immune-mediated pathways, which we supported by demonstrating the elevated expression of this cluster in serum of patients with other inflammatory conditions. The cluster contained miR-148a, a key driver of B-cell tolerance, and miR-365 that correlated with serum IgG and IgM concentrations. In addition, miR-29a and miR-223 were associated with blood lymphocyte and neutrophil populations, respectively. NHOL and IOI are characterized by an abnormal serum miRNA-cluster associated with immune pathway activation and linked to B cell and neutrophil dysfunction.

Zirconium-89-labelled rituximab PET-CT in orbital inflammatory disease.

BACKGROUND: Orbital inflammatory diseases are a heterogenic group of conditions that often entail a difficult diagnostic process and many patients are treatment resistant. Inflammatory diseases can be visualized by Zirconium-89-labelled rituximab PET-CT (89Zr-rituximab PET/CT). In this study, we describe our experience and possible potential of the 89Zr-rituximab PET/CT for diagnostic and therapeutic management of refractory orbital inflammation. RESULTS: Retrospectively, 89Zr-rituximab uptake was assessed and related to clinical data. The main outcome measures were the characteristics of the scan and the clinical relation of uptake with the diagnostic process and treatment effectivity. Twelve patients with thyroid eye disease (TED) and suspected idiopathic orbital inflammation (IOI) were scanned. Six patients had a strong 89Zr-rituximab uptake and showed a focal distribution within the lesion. Four patients (one TED, three IOI) responded well to rituximab treatment after a positive scan. 89Zr-rituximab PET/CT was essential to the diagnosis of optic nerve meningioma in one patient. CONCLUSION: 89Zr-rituximab PET/CT has the potential to be a powerful tool for the detection of B cell-mediated disease within the orbit and ocular adnexa. This technique can be a valuable addition for diagnosing diseases around the eye and can potentially predict rituximab treatment response in patients with refractory inflammation.

Perimesencephalic Hemorrhage: A Review of Epidemiology, Risk Factors, Presumed Cause, Clinical Course, and Outcome.

BACKGROUND AND PURPOSE: We systematically reviewed the literature on epidemiology, risk factors, presumed cause, clinical course, and outcome of perimesencephalic hemorrhage. METHODS: PubMed, Embase, and the Cochrane Library were searched until March 2016. Quality assessment was done by 2 authors independently. Pooled prevalence ratios and pooled odds ratios with 95% confidence intervals were calculated for data extracted from case-control studies. RESULTS: We included 208 papers. The incidence of perimesencephalic hemorrhage is ≈0.5 per 100.000 person-years, men are more often affected, and no risk factors were confirmed. Two decision analyses both found that a single, high-quality computed tomography angiography is the preferred diagnostic approach. Short-term complications, such as hydrocephalus or cranial nerve palsies, are rare, and usually transient, with the exception of acute symptomatic hydrocephalus necessitating treatment in 3% of patients. Lacunar infarcts in the brain stem were convincingly described in 4 patients only. Fatal rebleeding after installment of anticoagulation in the initial days after the hemorrhage was described in 1 patient. At long-term follow-up, death related to the hemorrhage has not been reported, disability is found in 0% to 6%, and neuropsychological sequelae are suggested. CONCLUSIONS: A single, high-quality computed tomography angiography is the preferred diagnostic strategy. Short-term complications are rare and often transient. Long-term outcome is excellent with respect to disability and death, but high-quality studies focused at neuropsychological sequelae are needed.

Single benign metastasising leiomyoma of an inguinal lymph node.

Benign metastasising leiomyoma (BML) is a rare benign disease associated with uterine leiomyoma and history of uterine surgery. It most frequently occurs in premenopausal woman, with a pulmonary localisation, and consisting of multiple nodules. We present an uncommon case of a 69-year-old woman with a single BML of an inguinal lymph node. CT scans of thorax and abdomen excluded other metastasis localisation. The patient was cured with surgical excision of the mass. Lymph node involvement has been reported incidentally in BML literature. Lymphangitic spread can be considered a possible mechanism of BML metastasis.

Patient- and Aneurysm-Specific Risk Factors for Intracranial Aneurysm Growth: A Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Follow-up imaging is often performed in intracranial aneurysms that are not treated. We performed a systematic review and meta-analysis on patient- and aneurysm-specific risk factors for aneurysm growth. METHODS: We searched EMBASE and MEDLINE for cohort studies describing risk factors for aneurysm growth. Two authors independently assessed study eligibility and rated quality with the Newcastle Ottawa Scale. With univariable Poisson regression analysis, we calculated risk ratios (RRs) with corresponding 95% confidence intervals (95% CI) of risk factors for aneurysm growth. Heterogeneity was assessed with I(2). RESULTS: Eighteen studies on 15 patient-populations described 3990 patients with 4972 unruptured aneurysms. A total of 437 aneurysms (9%) enlarged during 13 987 aneurysm-years of follow-up. Compared with aneurysms ≤4 mm, RRs were 2.56 (95% CI, 1.93-3.39; I(2)=98%) for ≥5 mm, 2.80 (95% CI, 2.01-3.90; I(2)=96%) for ≥7 mm, and 5.38 (95% CI, 3.76-7.70; I(2)=97%) for ≥10 mm. Compared with aneurysms on the middle cerebral artery, the RR for basilar artery was 1.94 (95% CI, 1.32-2.83; I(2)=57%). RRs were 2.03 (95% CI, 1.52-2.71; I(2)=59%) for smoking at baseline, 2.04 (95% CI, 1.56-2.66; I(2)=90%) for multiple unruptured aneurysms, 1.26 (95% CI, 0.97-1.62; I(2)=59%) for women, 1.24 (95% CI, 0.98-1.58; I(2)=40%) for hypertension, and 2.32 (95% CI, 1.46-3.68; I(2)=91%) for irregular aneurysm shape. Compared with other regions, RR was 0.75 (95% CI, 0.58-0.96) for Japan and 0.64 (95% CI, 0.45-0.90) for Finland. CONCLUSIONS: Most risk factors for aneurysm growth are consistent with risk factors for rupture. In contrast with rupture, the risk of growth was smaller in Japanese and Finnish cohorts compared with other regions. Pooling of individual patient data from low- and high-risk geographical regions is needed to assess independent predictors of aneurysm growth.

Prognostic Factors Associated with Visual Outcome after Pars Plana Vitrectomy with Internal Limiting Membrane Peeling for Idiopathic Epiretinal Membrane.

PURPOSE: Pars plana vitrectomy with internal limiting membrane peeling for idiopathic epiretinal membrane has shown varying results. More data are needed on the factors associated with visual outcome. METHODS: We extracted baseline clinical characteristics, optical coherence tomography (OCT) characteristics and 3-month postoperative best-corrected visual acuity (BCVA). Linear regression analysis was used to evaluate whether baseline and OCT characteristics are associated with BCVA at 3 months as well as BCVA difference. RESULTS: Out of 82 operated eyes, 66 (80%) had a 3-month follow-up, and 47 (71%) showed a 3-month postoperative improvement. Preoperative BCVA was an independent determinant of postoperative BCVA (r = 0.31; p < 0.01) and BCVA difference (r = 0.68; p < 0.01). Other baseline and OCT characteristics showed no independent associations with postoperative outcome. CONCLUSION: Better preoperative BCVA predicts better postoperative BCVA. Other baseline and OCT characteristics are not associated with visual outcome 3 months after surgery.

Effect of endothelin receptor antagonists on clinically relevant outcomes after experimental subarachnoid hemorrhage: a systematic review and meta-analysis.

In clinical trials, endothelin receptor antagonists (ETRAs) reduced vasospasm but did not improve functional outcome after subarachnoid hemorrhage (SAH). We assessed the effects of treatment with ETRAs on clinically relevant outcomes in animal studies modelling SAH by performing a systematic review of the literature for controlled animal studies of ETRAs for the treatment of SAH. Primary outcomes were neurobehavioral outcomes and case fatality. Secondary outcomes were cerebral vasospasm and cerebral blood flow. Summary estimates were calculated using normalized mean difference random effects meta-analysis. We included 27 studies (55 experiments, 639 animals). Neurobehavioral scores were reported in none of the experiments, and case fatality in 8 (15%). Treatment with ETRAs was associated with a pooled odds ratio for case fatality of 0.61 (95% confidence interval (CI), 0.27 to 1.39); a 54% increase (95% CI, 39 to 69) in cerebral arterial diameter; and a 93% increase (95% CI, 58 to 129) in cerebral blood flow. We conclude that there is no evidence from animal studies that treatment with an ETRA improves clinically relevant outcomes after SAH. The reduction in cerebral vasospasm observed in animal studies is consistent with that observed in clinical trials, an effect that is not associated with better functional outcome in patients.

Nosocomial infections after aneurysmal subarachnoid hemorrhage: time course and causative pathogens.

BACKGROUND: Nosocomial infections after aneurysmal subarachnoid hemorrhage (aSAH) are associated with prolonged length of stay and poor functional outcome. It remains unclear if infections result in prolonged length of stay or, vice versa, if prolonged length of stay results in more infections. Before strategies can be designed to reduce infections after aneurysmal subarachnoid hemorrhage, more data are needed on time course and causative pathogens of infections. AIM: To investigate the time course of infection onset and bacterial microorganisms that cause nosocomial infections after aSAH. METHODS: In consecutive patients with aneurysmal subarachnoid hemorrhage admitted to the University Medical Center Utrecht between 2009 and 2011, we analyzed the proportion of patients with infections, day of infection onset, and culture results. RESULTS: Of the 291 included patients, 107 (37%) patients developed 115 nosocomial infections. Fifty-six patients (19%) developed an infection within the first week. Median day of infection onset was for pneumonia (n = 49; 17%) day 4 (interquartile range 3-9), respiratory tract infection (n = 16; 6%) day 4 (interquartile range 1-7), urinary tract infection (n = 27; 9%) day 11 (interquartile range 7-14), and meningitis/ventriculitis (n = 10; 3%) day 19 (interquartile range 9-33). Cultures of infections mostly yielded Staphylococcus aureus (20%), Haemophilus influenzae (15%), and Escherichia coli (14%), CONCLUSION: Nosocomial infections after subarachnoid hemorrhage are common and mostly occur in the first week after ictus. Future studies should investigate if general hygienic measures, infection awareness, minimizing the duration of mechanical ventilation and use of catheters/drains, or prophylactic antibiotics reduce infections and improve functional outcome.