Low serum calcium is a novel predictor of unfavorable prognosis after traumatic brain injury.

Background: Accurate and convenient serological markers for prognosis after traumatic brain injury (TBI) are still lacking. We aimed to explore the predictive value of serum calcium for prognosing outcomes within 6 months after TBI. Methods: In this multicenter retrospective study, 1255 and 719 patients were included in development and validation cohorts, respectively, and their 6-month prognoses were recorded. Serum calcium was measured through routine blood tests within 24 h of hospital admission. Two multivariate predictive models with or without serum calcium for prognosis were developed. Receiver operating characteristics and calibration curves were applied to estimate their performance. Results: The patients with lower serum calcium levels had a higher frequency of unfavorable 6-month prognosis than those without. Lower serum calcium level at admission was associated with an unfavorable 6-month prognosis in a wide spectrum of patients with TBI. Lower serum calcium level and our prognostic model including calcium performed well in predicting the 6-month unfavorable outcome. The calcium nomogram maintained excellent performance in discrimination and calibration in the external validation cohort. Conclusions: Lower serum calcium level upon admission is an independent risk factor for an unfavorable 6-month prognosis after TBI. Integrating serum calcium into a multivariate predictive model improves the performance for predicting 6-month unfavorable outcomes.

Rapid Generation of Tetrahydropyridines and Tetrahydroquinolines by Dearomative Cyanation/Grignard Addition.

A rapid, practical and scalable method for the reductant and tansition-metal-free synthesis of a variety of novel 2,4-disubstituted tetrahydropyridines and tetrahydroquinolines is disclosed. The method is based upon dearomative functionalization of pyridines or quinolines to generate amino nitrile intermediates as masked iminium ions, which then react rapidly with various Grignard reagents in complete stereocontrol.

A Clinical Predictive Nomogram for Traumatic Brain Parenchyma Hematoma Progression.

INTRODUCTION: Acute traumatic intraparenchymal hematoma (tICH) expansion is a major cause of clinical deterioration after brain contusion. Here, an accurate prediction tool for acute tICH expansion is proposed. METHODS: A multicenter hospital-based study for multivariable prediction model was conducted among patients (889 patients in a development dataset and 264 individuals in an external validation dataset) with initial and follow-up computed tomography (CT) imaging for tICH volume evaluation. Semi-automated software was employed to assess tICH expansion. Two multivariate predictive models for acute tICH expansion were developed and externally validated. RESULTS: A total of 198 (22.27%) individuals had remarkable acute tICH expansion. The novel Traumatic Parenchymatous Hematoma Expansion Aid (TPHEA) model retained several variables, including age, coagulopathy, baseline tICH volume, time to baseline CT time, subdural hemorrhage, a novel imaging marker of multihematoma fuzzy sign, and an inflammatory index of monocyte-to-lymphocyte ratio. Compared with multihematoma fuzzy sign, monocyte-to-lymphocyte ratio, and the basic model, the TPHEA model exhibited optimal discrimination, calibration, and clinical net benefits for patients with acute tICH expansion. A TPHEA nomogram was subsequently introduced from this model to facilitate clinical application. In an external dataset, this device showed good predicting performance for acute tICH expansion. CONCLUSIONS: The main predictive factors in the TPHEA nomogram are the monocyte-to-lymphocyte ratio, baseline tICH volume, and multihematoma fuzzy sign. This user-friendly tool can estimate acute tICH expansion and optimize personalized treatments for individuals with brain contusion.

Neutrophil to lymphocyte ratio predicts early growth of traumatic intracerebral haemorrhage.

OBJECTIVE: The neutrophil to lymphocyte ratio (NLR) has been proposed to capture the inflammatory status of patients with various conditions involving the brain. This retrospective study aimed to explore the association between the NLR and the early growth of traumatic intracerebral haemorrhage (tICH) in patients with traumatic brain injury (TBI). METHODS: A multicentre, observational cohort study was conducted. Patients with cerebral contusion undergoing baseline computed tomography for haematoma volume analysis within 6 h after primary injury and follow-up visits within 48 h were included. Routine blood tests were performed upon admission, and early growth of tICH was assessed. Prediction accuracies of the NLR for the early growth of tICH and subsequent surgical intervention in patients were analysed. RESULTS: There were a total of 1077 patients who met the criteria included in the study cohort. Univariate analysis results showed that multiple risk factors were associated with the early growth of tICH and included in the following multivariate analysis models. The multivariate logistic regression analysis results revealed that the NLR was highly associated with the early growth of tICH (p < 0.001) while considering other risk factors in the same model. The prediction accuracy of the NLR for the early growth of tICH in patients is 82%. INTERPRETATION: The NLR is easily calculated and might predict the early growth of tICH for patients suffering from TBI.

Development and external validation of a novel multihematoma fuzzy sign on computed tomography for predicting traumatic intraparenchymal hematoma expansion.

Acute traumatic intraparenchymal hematoma (tICH) expansion is a devastating neurological complication that is associated with poor outcome after cerebral contusion. This study aimed to develop and validate a novel noncontrast computed tomography (CT) (NCCT) multihematoma fuzzy sign to predict acute tICH expansion. In this multicenter, prospective cohort study, multihematoma fuzzy signs on baseline CT were found in 212 (43.89%) of total 482 patients. Patients with the multihematoma fuzzy sign had a higher frequency of tICH expansion than those without (90.79% (138) vs. 46.71% (71)). The presence of multihematoma fuzzy sign was associated with increased risk for acute tICH expansion in entire cohort (odds ratio [OR]: 16.15; 95% confidence interval (CI) 8.85-29.47; P < 0.001) and in the cohort after propensity-score matching (OR: 9.37; 95% CI 4.52-19.43; P < 0.001). Receiver operating characteristic analysis indicated a better discriminative ability of the presence of multihematoma fuzzy sign for acute tICH expansion (AUC = 0.79; 95% CI 0.76-0.83), as was also observed in an external validation cohort (AUC = 0.76; 95% CI 0.67-0.84). The novel NCCT marker of multihematoma fuzzy sign could be easily identified on baseline CT and is an easy-to-use predictive tool for tICH expansion in the early stage of cerebral contusion.

The Monocyte-to-Lymphocyte Ratio at Hospital Admission Is a Novel Predictor for Acute Traumatic Intraparenchymal Hemorrhage Expansion after Cerebral Contusion.

PURPOSE: To explore the potential of monocyte-to-lymphocyte ratio (MLR) at hospital admission for predicting acute traumatic intraparenchymal hematoma (tICH) expansion in patients with cerebral contusion. Patients and Methods. This multicenter, observational study included patients with available at-hospital admission (baseline) and follow-up computed tomography for volumetric analysis (retrospective development cohort: 1146 patients; prospective validation cohort: 207 patients). Semiautomated software assessed tICH expansion (defined as ≥33% or 5 mL absolute growth). MLR was acquired from routine blood tests upon admission. We constructed two predictive models: basic combined model of clinical and imaging variables and MLR combined model of both MLR and other variables in the basic model. Receiver operating characteristic (ROC) analysis and decision curve analysis (DCA) were used to estimate the performance of MLR for predicting acute tICH expansion. RESULTS: MLR was significantly larger in patients with acute tICH expansion compared to those without acute tICH expansion (mean [SD], 1.08 [1.05] vs. 0.59 [0.37], P < 0.001). A nonlinear positive relationship between MLR and the incidence of acute tICH expansion was observed. Multivariate logistic regression indicated MLR as an independent risk factor for acute tICH expansion (odds ratio (OR), 5.88; 95% confidence interval (CI), 4.02-8.61). The power of the multivariate model for predicting acute tICH expansion was substantially improved with the inclusion of MLR (AUC 0.86 vs. AUC 0.74, P < 0.001), as was also observed in an external validation cohort (AUC 0.83 vs. AUC 0.71, P < 0.001). The net benefit of MLR model was higher between threshold probabilities of 20-100% in DCA. For clinical application, a nomogram derived from the multivariate model with MLR was introduced. In addition, MLR was positively associated with 6-month unfavorable outcome. CONCLUSION: MLR is a novel predictor for traumatic parenchymatous hematoma expansion. A nomogram derived from the MLR model may provide an easy-to-use tool for predicting acute tICH expansion and promoting the individualized treatment of patients with hemorrhagic cerebral contusion. MLR is associated with long-term outcome after cerebral contusion.

Strategic C-C Bond-Forming Dearomatization of Pyridines and Quinolines.

A one-pot protocol for the dearomative double nucleophilic addition to pyridines and quinolines, providing convenient, regioselective and diastereoselective access to tetrahydropyridines and tetrahydroquinolines under reductant-free conditions is described. This method also offers a new strategy for the general dearomatization of nitrogen heteroaromatics.

Design and discovery of thioether and nicotinamide containing sorafenib analogues as multikinase inhibitors targeting B-Raf, B-RafV600E and VEGFR-2.

New sorafenib derivatives containing thioether and nicotinamide moiety were designed and synthesized as B-Raf, B-RafV600E and VEGFR-2 multikinase inhibitors. Their in vitro enzymatic inhibitory activities against B-Raf, B-RafV600E and VEGFR-2 and their antiproliferative activities against HCT-116 and B16BL6 cell lines were evaluated and described. Most of the compounds showed potent activities against both cell lines and specific kinases. Compounds a1, b1 and c4, which exhibited the most potent inhibitory activities against B-Raf with IC50 of 21 nM, 27 nM and 17 nM, B-RafV600E with IC50 of 29 nM, 28 nM and 16 nM, VEGFR-2 with IC50 of 84 nM, 46 nM and 63 nM, respectively, and good antiproliferative activities, also demonstrated competitive antiangiogenic activities to sorafenib in in vitro HUVEC tube formation assay.

Paradoxical Herniation after Unilateral Decompressive Craniectomy: A Retrospective Analysis of Clinical Characteristics and Effectiveness of Therapeutic Measures.

AIM: We aimed to investigate the importance of early diagnosis and proper management of paradoxical herniation based on the data of 13 patients who had 14 occurrences of paradoxical herniation. MATERIAL AND METHODS: The characteristics and the effectiveness of treatments of 13 patients with paradoxical herniation were reviewed and analyzed retrospectively. RESULTS: Paradoxical herniation occurred in eight patients (61.54%) during the postoperative 2 weeks and they presented with typical symptoms of brain herniation and a tense skin flap without sinking at the region of decompressive craniectomy. On the other hand, six patients developed paradoxical herniation in the postoperative period of 2 weeks to 2 months and presented with sinking skin flaps and delayed neurological deficits. Furthermore, all patients received emergency treatments, including sufficient hydration, clamping cerebrospinal fluid (CSF) drainage, and being placed in the Trendelenburg position. Six patients achieved full neurologic recovery after successful cranioplasty. CONCLUSION: Intracranial hypotension causing paradoxical herniation can rapidly progress, especially along with CSF depletion. It is important for neurosurgeons to suspect paradoxical herniation in a subset of patients with large cranium defects and tense skin flap without sinking during the postoperative 2 weeks. Paradoxical herniation is rapidly reverted by improving CSF hydration, and performing early cranioplasty referred as the definitive treatment.

Paradoxical Herniation After Unilateral Decompressive Craniectomy Predicts Better Patient Survival: A Retrospective Analysis of 429 Cases.

Paradoxical herniation (PH) is a life-threatening emergency after decompressive craniectomy. In the current study, we examined patient survival in patients who developed PH after decompressive craniectomy versus those who did not. Risk factors for, and management of, PH were also analyzed. This retrospective analysis included 429 consecutive patients receiving decompressive craniectomy during a period from January 2007 to December 2012. Mortality rate and Glasgow Outcome Scale (GOS) were compared between those who developed PH (n = 13) versus those who did not (n = 416). A stepwise multivariate logistic regression analysis was carried out to examine the risk factors for PH. The overall mortality in the entire sample was 22.8%, with a median follow-up of 6 months. Oddly enough, all 13 patients who developed PH survived beyond 6 months. Glasgow Coma Scale did not differ between the 2 groups upon admission, but GOS was significantly higher in subjects who developed PH. Both the disease type and coma degree were comparable between the 13 PH patients and the remaining 416 patients. In all PH episodes, patients responded to emergency treatments that included intravenous hydration, cerebral spinal fluid drainage discontinuation, and Trendelenburg position. A regression analysis indicated the following independent risk factors for PH: external ventriculostomy, lumbar puncture, and continuous external lumbar drainage. The rate of PH is approximately 3% after decompressive craniectomy. The most intriguing findings of the current study were the 0% mortality in those who developed PH versus 23.6% mortality in those who did not develop PH and significant difference of GOS score at 6-month follow-up between the 2 groups, suggesting that PH after decompressive craniectomy should be managed aggressively. The risk factors for PH include external ventriculostomy, ventriculoperitoneal shunt, lumbar puncture, and continuous external lumbar drainage.

Clinical use of a neuronavigation system in hemangioblastoma resection of posterior cranial fossa.

The aim of this study was to retrospectively evaluate the effectiveness of the Stryker Leibinger neuronavigation system in surgical resection of hemangioblastomas of the posterior fossa. The study included 16 cases of solid hemangioblastoma of posterior cranial fossa treated since we began using Stryker Leibinger neuronavigation system-assisted microneurosurgery in 2003. These cases were compared on the basis of time, blood loss, and complications to 19 similar cases of solid hemangioblastoma that underwent conventional microneurosurgical resection prior to 2003. All patients in the experimental (neuronavigation-assisted) group underwent surgical resection without complications while the control groups' resections all involved blood loss related to the longer operation time. Neuronavigation also resulted in a clear field of surgical vision and clear lesion boundaries, making it easier to remove lesions and reduce accidental injury of adjacent normal structures. The application of navigation technology is very valuable for solid hemangioblastoma operations not only by shortening operative time, thereby significantly reducing operative blood loss, but also by making surgical excision easier, reducing damage to adjacent normal structures, and decreasing surgical complications and mortality.

Efficacy of subdural saline injection during surgery for acute epidural haematomas.

PRIMARY OBJECTIVE: The purpose of this study was to investigate the efficacy of subdural space saline injection surgery in the management of large acute epidural haematomas (EDHs). METHODS AND PROCEDURES: Over a period of 6 years, the authors employed the technique of subdural space saline injection to facilitate elevation of dura after evacuation of supratentorial epidural haematomas. MAIN OUTCOMES AND RESULTS. Eighty patients with supratentorial epidural haematomas underwent the procedure. Infusion of saline in the subdural space not only helps elevation of the dura, facilitate haemostasis and application of suspension stitches during operation, it also avoids ICP fluctuations during the operations. Post-operative CT scans showed rapid disappearance of saline and reposition of cerebral structure. No patient required re-operation for residual haematoma. CONCLUSIONS: Subdural saline injection is an effective operative technique in the management of large epidural haematoma.