In neurosurgical perioperative treatment, especially in connection with subarachnoid hemorrhage (SAH), the prophylactic anticoagulation (AC) regimen is still considered controversial. The goal of ...this retrospective study was to assess how the time point of low-molecular-weight heparin (LMWH) initiation (ToH) affects ischemic and hemorrhagic events after SAH.
370 patients who received acute treatment for non-traumatic SAH between 2011 and 2018 were included, and 208 patients were followed up after 12 months. We assessed how the ToH affects ischemic and hemorrhagic events as well as outcome scores. Statistical analysis was performed using the Mann-Whitney U-Test, the chi-squared test, Fisher’s exact test, and univariate binomial logistic regression. P-values below 0.05 were considered statistically significant.
The incidence of systemic ischemia was 4.6%, cerebral ischemia 33.5%, and intracranial rebleeding 14.6%. Delaying ToH (measured in hours) increases systemic ischemia (p = 0.009). The odds ratio for the impact of delayed anticoagulation on systemic ischemia is 1.013 per hour (95%CI of OR 1.001–1.024). ToH has no influence on cerebral ischemia or intracranial rebleeding. Early anticoagulation was associated with a more favorable Glasgow Outcome Score 12 months after discharge (ToH within 48 h: p = 0.006). ToH did not affect mortality or readmission rates.
Initiating prophylactic AC with LMWH later than 48 h after aneurysm repair or admission impairs outcomes 12 months after discharge. It might be safe for patients with non-traumatic SAH to be anticoagulated with prophylactic doses of heparin within 24 h after admission or the treatment of source of bleeding (SoB). Early AC with prophylactic LMWH does not promote rebleeding.
•This study highlights the ideal onset of prophylactic anticoagulation in subarachnoid hemorrhage.•The time of onset of AC has no influence on cerebral ischemia or intracranial rebleeding.•Early anticoagulation was associated with a more favorable Glasgow Outcome Score 12 months after discharge.
Background
It is suspected that microbiome-derived trimethylamine N-oxide (TMAO) may enhance platelet responsiveness and accordingly be thrombophilic. The purpose of this prospective observational ...study is to evaluate TMAO in patients with subarachnoid hemorrhage (SAH) and compare it with a control group. A secondary aim was to investigate TMAO in the cerebrospinal fluid (CSF) from SAH patients. This should provide a better understanding of the role of TMAO in the pathogenesis of SAH and its thrombotic complications.
Methods
The study included patients with diagnosed spontaneous SAH recruited after initial treatment on admission and patients with nerve, nerve root, or plexus disorders serving as controls. Blood samples were gathered from all patients at recruitment. Additionally, sampling of SAH patients in the intensive care unit continued daily for 14 days. The CSF was collected out of existing external ventricular drains whenever possible.
Results
Thirty-four patients diagnosed with SAH, and 108 control patients participated in this study. Plasma TMAO levels at baseline were significantly lower in the SAH group (1.7 μmol/L) compared to the control group (2.9 μmol/L). TMAO was detectable in the CSF (0.4 μmol/L) and significantly lower than in plasma samples of the SAH group at baseline. Plasma and CSF TMAO levels correlated positively. The TMAO levels did not differ significantly during the observation period of 15 days.
Conclusions
Although we assumed that patients with higher TMAO levels were at higher risk for SAH a priori, plasma TMAO levels were lower in patients with SAH compared with control subjects with nerve, nerve root, or plexus disorders on admission to the hospital. A characteristic pattern of plasma TMAO levels in patients with SAH was not found.
•An alternative Active Contour Model solution for medical images is introduced.•A multi-population Cuckoo Search Strategy (MCSS) is implemented to boost ACM.•Proposed method was applied on Magnetic ...Resonance Imaging (MRI) data.•MCSS outperforms traditional ACM and ACM driven by multi-population PSO.
In this paper, an alternative Active Contour Model (ACM) driven by Multi-population Cuckoo Search (CS) algorithm is introduced. This strategy assists the converging of control points towards the global minimum of the energy function, unlike the traditional ACM version which is often trapped in a local minimum. In the proposed methodology, each control point is constrained in a local search window, and its energy minimisation is performed through a Cuckoo Search via Lévy flights paradigm. With respect to local search window, two shape approaches have been considered: rectangular shape and polar coordinates. Results showed that the CS method using polar coordinates is generally preferable to CS performed in rectangular shapes. Real medical and synthetic images were used to validate the proposed strategy, through three performance metrics as the Jaccard index, the Dice index and the Hausdorff distance. Applied specifically to Magnetic Resonance Imaging (MRI) images, the proposed method enables to reach better accuracy performance than the traditional ACM formulation, also known as Snakes and the use of Multi-population Particle Swarm Optimisation (PSO) algorithm.
Summary
Background
ERELATE was a phase 4, multinational, retrospective, observational study.
Aim
To evaluate the relationship between intravenous vedolizumab exposure and treatment outcomes over 52 ...weeks in adults with ulcerative colitis (UC) or Crohn’s disease (CD).
Methods
Real‐world data from patients with UC or CD treated with intravenous vedolizumab in nine centres in six countries were collected retrospectively. Treatment outcomes were collected at Weeks 14, 26 and 52. An established population pharmacokinetic model (incorporating observed vedolizumab concentrations based on a Bayesian approach) was used to predict individual vedolizumab exposure. Vedolizumab exposure–response relationship was evaluated overall, by indication and based on baseline characteristics.
Results
The study population (n = 695; UC, n = 304; CD, n = 391) had a median age of 39 years; 47.9% were male and 86.9% had prior tumour necrosis factor antagonist exposure. By Week 14, clinical, endoscopic, deep (clinical plus endoscopic) and biologic remission was achieved by 47.3%, 59.6%, 30.7% and 19.0% of patients respectively. Higher vedolizumab trough concentration early in treatment was consistently associated with clinical remission at later time points. Clinical remission at Week 14 and Week 52 was associated with Week 6 trough concentrations of ≥31.0 and ≥32.0 μg/ml respectively. Importantly, multivariable analysis identified baseline clearance as the only exposure measure predictive of clinical and deep remission at Week 52.
Conclusions
In this real‐world study, a positive exposure–response relationship was observed for vedolizumab. Vedolizumab concentration during induction may be an important predictor of short‐ and long‐term outcomes, and similarly, vedolizumab baseline clearance may be an important predictor of remission.
Vedolizumab (VDZ) is an anti-α 4 β 7 integrin monoclonal antibody approved for inflammatory bowel disease treatment. VDZ serum and antidrug antibody (ADA) concentrations may be used for treatment ...optimization. In this article, the results of 5 commercial assays (Grifols, Immundiagnostik, Progenika, Sanquin, and Theradiag) measuring VDZ concentration and ADA were compared with those of the reference assays used in VDZ clinical studies. Our findings will assist clinicians in interpreting commercial assay results in the context of VDZ clinical trial data.
VDZ-treated patient samples were used to evaluate the agreement between commercial assays and the reference VDZ serum concentration assay, based on linear regression, Bland-Altman, and qualitative agreement analyses. VDZ ADAs were detected using qualitative assays. Specificity, selectivity, accuracy, and precision were assessed using serum samples from healthy donors or patients with IBD (VDZ serum concentration <0.5 mcg/mL) spiked with VDZ, with/without other biologics (identical sample sets per assay).
All assays were specific and selective for VDZ. Overall, the commercial assay results for VDZ-spiked samples correlated well with those of the reference serum concentration assay (R 2 ≥ 0.98). Compared with the Immundiagnostik and Theradiag assays, the Grifols, Sanquin, and Progenika assays had the best reference assay agreement (based on regression analysis, Bland-Altman plots, and qualitative agreement Cohen's kappa ≥0.92). All immunogenicity assays detected VDZ ADAs; only the reference assay detected VDZ ADAs in the presence of 15 mcg/mL VDZ, advising caution with commercial ADA assays if VDZ is present.
All 5 commercial assays are suitable for VDZ therapeutic monitoring and ADA testing. However, the absolute values from the reference assays and the different commercial assays were not comparable, indicating that the same assay must be used for repeated monitoring of VDZ serum concentrations.
Abstract
Background
Crohn’s disease CD is a chronic inflammatory bowel disease that, with progression, may require surgical intervention.
Aim
To determine whether vedolizumab treatment of CD earlier ...in the disease course ≤2 or ≤5 years of disease duration influences risk of CD-related surgery after accounting for probability of response.
Methods
Post hoc analyses of data from CD patients treated with vedolizumab in the GEMINI 2, GEMINI 3, and GEMINI LTS trials N = 1253 evaluated CD-related surgery bowel resection or colectomy with stratification by probability of response to vedolizumab low/intermediate or high. Analyses used a previously validated clinical decision support tool and both logistic regression and Cox proportional hazard analyses.
Results
In total, 113 9.0% vedolizumab-treated patients required CD-related surgery. Surgical rates were 6.1% and 9.8% for the high and low/intermediate probability of response groups, respectively. Risk of surgery was lower for patients with a high probability of response versus those with a low/intermediate probability of response (hazard ratio HR 0.50, 95% confidence interval CI 0.29 to 0.85). For patients with a low/intermediate probability of vedolizumab response, there was a consistent trend for association between earlier treatment ≤2 or ≤5 years since diagnosis and a lower risk of surgery relative to later treatment (≤2 years versus >2 years: odds ratio OR 0.77, 95% CI 0.38 to 1.58; ≤5 years versus >5 years: OR 0.61, 95% CI 0.37 to 1.00.
Conclusions
Earlier intervention with vedolizumab may be associated with lower rates of surgery. Use of the clinical decision support tool may help identify patients most likely to benefit from earlier intervention with vedolizumab.
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