To intoxicated patients in the emergency room, toxicological analysis can be considerably helpful for identifying the involved toxicants. In order to develop a urine multi-drug screening (UmDS) method, gas chromatography–mass spectrometry (GC-MS) and liquid chromatography–tandem mass spectrometry (LC–MS-MS) were used to determine targeted and unknown toxicants in urine. A GC-MS method in scan mode was validated for selectivity, limit of detection (LOD) and recovery. An LC–MS-MS multiple reaction monitoring (MRM) method was validated for lower LOD, recovery and matrix effect. The results of the screening analysis were compared with patient medical records to check the reliability of the screen. Urine samples collected from an emergency room were extracted through a combination of salting-out assisted liquid–liquid extraction (SALLE) and hybrid protein precipitation/solid phase extraction (hybrid PPT/SPE) plates and examined by GC-MS and LC–MS-MS. GC-MS analysis was performed as unknown drug screen and LC–MS-MS analysis was conducted as targeted drug screen. After analysis by GC-MS, a library search was conducted using an in-house library established with the automated mass spectral deconvolution and identification system (AMDISTM). LC–MS-MS used Cliquid®2.0 software for data processing and acquisition in MRM mode. An UmDS method by GC-MS and LC–MS-MS was developed by using a SALLE-hybrid PPT/SPE and in-house library. The results of UmDS by GC-MS and LC–MS-MS showed that toxicants could be identified from 185 emergency room patient samples containing unknown toxicants. Zolpidem, acetaminophen and citalopram were the most frequently encountered drugs in emergency room patients. The UmDS analysis developed in this study can be used effectively to detect toxic substances in a short time. Hence, it could be utilized in clinical and forensic toxicology practices.
Background: This study aimed to quantitatively analyse ultra-early brain diffusion-weighted magnetic resonance imaging (DW-MRI) findings to determine the apparent diffusion coefficient (ADC) threshold associated with neurological outcomes in comatose survivors of out-of-hospital cardiac arrest (OHCA). Methods: This retrospective study included adult survivors of comatose OHCA who underwent DW-MRI imaging scans using a 3-T MRI scanner within 6 h of the return of spontaneous circulation (ROSC). We investigated the association between neurological outcomes and ADC values obtained through voxel-based analysis on DW-MRI. Additionally, we constructed multivariable logistic regression models with pupillary light reflex (PLR), serum neuron-specific enolase (NSE), and ADC values as independent variables to predict poor neurological outcomes. The primary outcome was poor neurological outcome 6 months after ROSC, determined by the Cerebral Performance Category 3–5. Results: Overall, 131 patients (26% female) were analysed, of whom 74 (57%) showed poor neurological outcomes. The group with a poor neurological outcome had lower mean whole brain ADC values (739.1 vs. 787.1 × 10–6 mm/s) and higher percentages of voxels with ADC below threshold in all ranges (250–1150) (all P < 0.001). The mean whole brain ADC values (area under the receiver operating characteristic curve [AUC] 0.83) and the percentage of voxels with ADC below 600 (AUC 0.81) had the highest sensitivity of 51% (95% confidence interval [CI] 39.4–63.1; cut-off value ≤ 739.2 × 10−6 mm2/s and > 17.2%, respectively) when the false positive rate (FPR) was 0%. In the multivariable model, which also included PLR, NSE, and mean whole brain ADC values, poor neurological outcome was predicted with the highest accuracy (AUC 0.91; 51% sensitivity). This model showed more accurate prediction and sensitivity at an FPR of 0% than did the combination of PLR and NSE (AUC 0.86; 30% sensitivity; P = 0.03). Conclusions: In this cohort study, early voxel-based quantitative ADC analysis after ROSC was associated with poor neurological outcomes 6 months after cardiac arrest. The mean whole brain ADC value demonstrated the highest sensitivity when the FPR was 0%, and including it in the multivariable model improved the prediction of poor neurological outcomes.
We examined whether combining biomarkers measurements and brain images early after the return of spontaneous circulation improves prognostic performance compared with the use of either biomarkers or brain images for patients with cardiac arrest following target temperature management (TTM). This retrospective observational study involved comatose out-of-hospital cardiac arrest survivors. We analyzed neuron-specific enolase levels in serum (NSE) or cerebrospinal fluid (CSF), grey-to-white matter ratio by brain computed tomography, presence of high signal intensity (HSI) in diffusion-weighted imaging (DWI), and voxel-based apparent diffusion coefficient (ADC). Of the 58 patients, 33 (56.9%) had poor neurologic outcomes. CSF NSE levels showed better prognostic performance (area under the curve (AUC) 0.873, 95% confidence interval (CI) 0.749–0.950) than serum NSE levels (AUC 0.792, 95% CI 0.644–0.888). HSI in DWI showed the best prognostic performance (AUC 0.833, 95% CI 0.711–0.919). Combining CSF NSE levels and HSI in DWI had better prognostic performance (AUC 0.925, 95% CI 0.813–0.981) than each individual method, followed by the combination of serum NSE levels and HSI on DWI and that of CSF NSE levels and the percentage of voxels of ADC (AUC 0.901, 95% CI 0.792–0.965; AUC 0.849, 95% CI 0.717–0.935, respectively). Combining CSF/serum NSE levels and HSI in DWI before TTM improved the prognostic performance compared to either each individual method or other combinations.
This study aimed to determine whether accuracy and sensitivity concerning neurological prognostic performance increased for survivors of out-of-hospital cardiac arrest (OHCA) treated with targeted temperature management (TTM), using OHCA and cardiac arrest hospital prognosis (CAHP) scores and modified objective variables. We retrospectively analyzed non-traumatic OHCA survivors treated with TTM. The primary outcome was poor neurological outcome at 3 months after return of spontaneous circulation (cerebral performance category, 3–5). We compared neurological prognostic performance using existing models after adding objective data obtained before TTM from computed tomography (CT), magnetic resonance imaging (MRI), and biomarkers to replace the no-flow time component of the OHCA and CAHP models. Among 106 patients, 61 (57.5%) had poor neurologic outcomes. The area under the receiver operating characteristic (AUROC) curve for the OHCA and CAHP models was 0.89 (95% confidence interval (CI) 0.81–0.94) and 0.90 (95% CI 0.82–0.95), respectively. The prediction of poor neurological outcome improved after replacing no-flow time with a grey/white matter ratio measured using CT, high-signal intensity (HSI) on diffusion-weighted MRI (DWI), percentage of voxel using apparent diffusion coefficient value, and serum neuron-specific enolase levels. When replaced with HSI on DWI, the AUROC and sensitivity of the OHCA and CAHP models were 0.96 and 74.5% and 0.97 and 83.8%, respectively (100% specificity). Prognoses concerning neurologic outcomes improved compared with existing OHCA and CAHP models by adding new objective variables to replace no-flow time. External validation is required to generalize these results in various contexts.