Ana Kowark’s research while affiliated with University of Bonn and other places

Background Morphological analysis of intracranial pressure (ICP) pulse waveforms provides indirect information on cerebrospinal compliance, which might be reduced by space-occupying lesions but also by intracranial hypertension and aging. This study investigates the impact of age and mean ICP on the shape and amplitude of ICP pulse waveform in traumatic brain injury (TBI). Additionally, it explores the association between morphological parameters and mortality after TBI. Methods ICP recordings from 183 TBI patients (median age: 50 (30, 61) years) from the CENTER-TBI database were retrospectively analyzed. ICP morphology was assessed using the artificial intelligence-based pulse shape index (PSI) and peak-to-peak amplitude of ICP pulse waveform (AmpICP). The impact of mean ICP, age, and their interaction on PSI and AmpICP were estimated using factorial ANOVA. To account for influence of disturbance in the intracranial volume on AmpICP and PSI, a multiple regression analysis was performed using age, mean ICP, and the Rotterdam CT score as explanatory variables. The associations of AmpICP and PSI with six-month mortality were assessed using the area under the ROC curve (AUC). Results Age had a predominant influence on PSI ( p < 0.01), accounting for 33.1% of its variance, while mean ICP explained 6.6% ( p < 0.01). Conversely, mean ICP primarily affected AmpICP ( p < 0.01), explaining 22.8% of its variance, with age contributing 8.0% ( p < 0.01). A combined effect of age and mean ICP on AmpICP ( p = 0.01) explained 11.7% of its variance but did not influence PSI. After accounting for Rotterdam CT score, the results remained consistent, indicating that advanced age has the strongest impact on PSI (β = 0.342, p < 0.01) while elevated mean ICP has dominant influence on AmpICP (β = 0.522, p < 0.01). Both AmpICP and PSI were moderately associated with mortality (AUC: 0.76 and 0.71, respectively). Conclusions AmpICP and PSI capture distinct aspects of cerebrospinal compliance. PSI appears to reflect age-related stiffening of the cerebrovascular system, while AmpICP, influenced by mean ICP, indicates acute volume compensatory changes. Combined, they provide a more comprehensive assessment of cerebrospinal volume–pressure compensation. Both morphological metrics are associated with mortality after TBI. As cerebrospinal compliance declines with age, older TBI patients become more susceptible to uncontrolled rises in ICP, which can worsen their outcome.

Background Hyperlipidemia has been implicated in the higher risk of developing postoperative delirium. Prostaglandin endoperoxide synthase-2 mediates neuroinflammatory processes in postoperative delirium. This study aims to investigate whether preoperative administration of parecoxib is more efficient than a placebo in averting postoperative delirium in patients with hyperlipidemia. Materials and methods In this randomized, double-blind, superiority trial, participants with hyperlipidemia were randomized in a 1:1 ratio to receive parecoxib (40 mg parecoxib administered intravenously before anesthesia induction) or placebo (normal saline). The primary outcome was postoperative delirium incidence within three days, with a 5.4% difference set as the superiority threshold. Secondary outcomes were cumulative incidences of emergence delirium and prostaglandin endoperoxide synthase-2 levels, inflammatory cell counts, and pain score on postoperative day 1 and postoperative adverse events. Results This trial conducted between August 2023 and August 2024 at a tertiary hospital in China included 452 adults with hyperlipidemia, with 226 in the parecoxib group and 226 in the placebo group. The incidence of postoperative delirium in the parecoxib group was 13.72%, a reduction of 12.39% compared to the placebo group (hazard ratio, 0.491; 95% confidence interval: 0.318 to 0.759; P < 0.001). The parecoxib group also had a lower incidence of emergence delirium, prostaglandin endoperoxide synthase-2 levels, white blood cell counts and neutrophil, and pain scores on postoperative day 1. The occurrence of adverse events was comparable between the two groups. Prostaglandin endoperoxide synthase-2 expression levels, white blood cell counts, and pain scores mediated the reduction of postoperative delirium incidence by parecoxib. Conclusion Parecoxib may help in reducing the hyperlipidemia-related postoperative delirium incidence. The effective anti-inflammatory activity of prostaglandin endoperoxide synthase-2 inhibition by parecoxib and postoperative pain control may be important mechanisms for preventing postoperative delirium.

Background Traumatic brain injury (TBI) can significantly disrupt autonomic nervous system (ANS) regulation, increasing the risk for secondary complications, hemodynamic instability, and adverse outcome. This retrospective study evaluated windowed time-lagged cross-correlation (WTLCC) matrices for describing cerebral hemodynamics–ANS interactions to predict outcome, enabling identifying high-risk patients who may benefit from enhanced monitoring to prevent complications. Methods The first experiment aimed to predict short-term outcome using WTLCC-based convolution neural network models on the Wroclaw University Hospital (WUH) database (P training = 31 with 1,079 matrices, P val = 16 with 573 matrices). The second experiment predicted long-term outcome, training on the CENTER-TBI database (P training = 100 with 17,062 matrices) and validating on WUH (P val = 47 with 6,220 matrices). Cerebral hemodynamics was characterized using intracranial pressure (ICP), cerebral perfusion pressure (CPP), pressure reactivity index (PRx), while ANS metrics included low-to-high-frequency heart rate variability (LF/HF) and baroreflex sensitivity (BRS) over 72 h. Short-term outcome at WUH was assessed using the Glasgow Outcome Scale (GOS) at discharge. Long-term outcome was evaluated at 3 months at WUH and 6 months at CENTER-TBI using GOS and GOS-Extended, respectively. The XGBoost model was used to compare performance of WTLCC-based model and averaged neuromonitoring parameters, adjusted for age, Glasgow Coma Scale, major extracranial injury, and pupil reactivity in outcome prediction. Results For short-term outcome prediction, the best-performing WTLCC-based model used ICP-LF/HF matrices. It had an area under the curve (AUC) of 0.80, vs. 0.71 for averages of ANS and cerebral hemodynamics metrics, adjusted for clinical metadata. For long-term outcome prediction, the best-score WTLCC-based model used ICP-LF/HF matrices. It had an AUC of 0.63, vs. 0.66 for adjusted neuromonitoring parameters. Conclusions Among all neuromonitoring parameters, ICP and LF/HF signals were the most effective in generating the WTLCC matrices. WTLCC-based model outperformed adjusted neuromonitoring parameters in short-term but had moderate utility in long-term outcome prediction.

Background Post-traumatic stress disorder (PTSD) and depression are common after mild traumatic brain injury (mTBI), but their biological drivers are uncertain. We therefore explored whether polygenic risk scores (PRS) derived for PTSD and major depressive disorder (MDD) are associated with the development of cognate TBI-related phenotypes. Methods Meta-analyses were conducted using data from two multicenter, prospective observational cohort studies of patients with mTBI: the CENTER-TBI study (ClinicalTrials.gov ID NCT02210221) in Europe (December 2014–December 2017) and the TRACK-TBI study in the US (March 2014–July 2018). In both cohorts, the most common causes of injury were road traffic accidents and falls. Primary outcomes, specifically probable PTSD and depression, were defined at 6 months post-injury using scores ≥33 on the PTSD Checklist-5 and ≥15 on the Patient Health Questionnaire-9, respectively. We calculated PTSD-PRS and MDD-PRS for patients aged ≥17 years who had a Glasgow Coma Scale score of 13–15 upon hospital arrival and assessed their association with PTSD and depression following TBI. We also evaluated the transferability of the findings in a cohort of African Americans. Findings Overall, 11.8% (219/1869) and 6.7% (124/1869) patients were classified as having probable PTSD and depression, respectively. The PTSD-PRS was significantly associated with higher adjusted odds of PTSD in both cohorts, with a pooled odds ratio (OR) of 1.55 [95% confidence interval (CI) 1.30–1.84, p < 0.001, I² = 20.8%]. Although the MDD-PRS increased the risk of depression after TBI, it did not reach significance in the individual cohorts. However, in a combined analysis, the risk was significantly elevated with a pooled OR of 1.26 [95% CI 1.03–1.53, p = 0.02, I² = 0%]. The addition of PRSs improved the proportion of outcome variance explained in the two study cohorts from 19.5% and 30.3% to 21.6% and 34.0% for PTSD; and from 11.0% and 22.5% to 12.8% and 22.6% for depression. Patients in the highest cognate PRS quintile had increased odds of 3.16 [95% CI 1.80–5.55] and 2.03 [95% CI 1.04–3.94] of developing PTSD or depression compared to the lowest quintile, respectively. Interpretation Associations of PRSs with PTSD and depression following TBI are not disorder-specific. However, the overlap between MDD-PRS and depression following TBI is less robust compared to PTSD-PRS and PTSD. PRSs could improve risk prediction, and permit enrichment for interventional trials. Funding This study was supported by funding by an FP7 grant from the 10.13039/501100000780European Union, 10.13039/501100007731Hannelore Kohl Stiftung, 10.13039/100009006Integra LifeSciences Corporation, NeuroTrauma Sciences, US 10.13039/100000002National Institutes of Health, US 10.13039/100000005Department of Defense, National Football League Advisory Board, US 10.13039/100000015Department of Energy, and 10.13039/100018727One Mind.

Background Even patients with normal computed tomography (CT) head imaging may experience persistent symptoms for months to years after mild traumatic brain injury (mTBI). There is currently no good way to predict recovery and triage patients who may benefit from early follow-up and targeted intervention. We aimed to assess if existing prognostic models can be improved by serum biomarkers or diffusion tensor imaging metrics (DTI) from MRI, and if serum biomarkers can identify patients for DTI. Methods We included 1025 patients aged >18 years with a Glasgow Coma Score >12 and normal CT from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study which recruited between December 19,2014 and December 17, 2017 (NCT02210221). Biomarkers (GFAP, NFL, S100B) were obtained at a median of 8.8 h (Q1–Q3 4.2–16.7) and DTI at 13 days (3–19) after injury. DTI metrics were available in 153 patients for 48 white matter tracts (ICBM-DTI-81 atlas). Incomplete recovery at three months was defined as an extended Glasgow Outcome Scale score <8. Existing prognostic models were fitted with and without biomarkers, or with and without DTI, and internally validated using bootstrapping. Findings 385 (38%) patients had incomplete recovery. Adding biomarkers did not improve performance beyond the best existing clinical prognostic model [optimism-corrected AUC 0.69 (95% CI 0.65–0.72) and R² 17% (11–22)]. Adding DTI metrics significantly enhanced all models [best optimism-corrected AUC 0.82 (0.79–0.85) and R² 75% (39–100)]. The top three prognostic tracts were the left posterior thalamic radiation, left superior cerebellar peduncle and right uncinate fasciculus. Serum biomarkers could have avoided 1 in 5 DTI scans, with GFAP <12 h and NFL 12–24 h from injury performing best. Interpretation DTI substantially improved existing prognostic models for functional outcome in patients with mTBI and a normal CT, and biomarkers could help select patients for MRI. If validated, DTI could allow for targeted follow-up and enrichment of clinical trials of early interventions to improve outcome. Funding EU Seventh Framework Programme, 10.13039/501100007731Hannelore Kohl Stiftung, 10.13039/100018727One Mind, 10.13039/100009006Integra LifeSciences, NeuroTrauma Sciences.