Hyperbaric Oxygen Therapy Reduces the Traumatic Brain Injury-Mediated Neuroinflammation Through Enrichment of Prevotella Copri in the Gut of Male Rats.

BACKGROUND: Gastrointestinal dysfunction frequently occurs following traumatic brain injury (TBI) and significantly increases posttraumatic complications. TBI can lead to alterations in gut microbiota. The neuroprotective effects of hyperbaric oxygen (HBO) have not been well recognized after TBI. The study''s aim was to investigate the impact of HBO on TBI-induced dysbiosis in the gut and the pathological changes in the brain following TBI. METHODS: Anesthetized male Sprague-Dawley rats were randomly assigned to three groups: sham surgery plus normobaric air (21% oxygen at 1 atmospheres absolute), TBI (2.0 atm) plus normobaric air, and TBI (2.0 atm) plus HBO (100% oxygen at 2.0 atmospheres absolute) for 60 min immediately after TBI, 24 h later, and 48 h later. The brain injury volume, tumor necrosis factor-α expression in microglia and astrocytes, and neuronal apoptosis in the brain were subsequently determined. The V3-V4 regions of 16S ribosomal rRNA in the fecal samples were sequenced, and alterations in the gut microbiome were statistically analyzed. All parameters were evaluated on the 3rd day after TBI. RESULTS: Our results demonstrated that HBO improved TBI-induced neuroinflammation, brain injury volume, and neuronal apoptosis. HBO appeared to increase the abundance of aerobic bacteria while inhibiting anaerobic bacteria. Intriguingly, HBO reversed the TBI-mediated decrease in Prevotella copri and Deinococcus spp., both of which were negatively correlated with neuroinflammation and brain injury volume. TBI increased the abundance of these gut bacteria in relation to NOD-lik0065 receptor signaling and the proteasome pathway, which also exhibited a positive correlation trend with neuro inflammation and apoptosis. The abundance of Prevotella copri was negatively correlated with NOD-like receptor signaling and the Proteasome pathway. CONCLUSIONS: Our study demonstrated how the neuroprotective effects of HBO after acute TBI might act through reshaping the TBI-induced gut dysbiosis and reversing the TBI-mediated decrease of Prevotella copri.

Machine Learning Algorithm Predicts Mortality Risk in Intensive Care Unit for Patients with Traumatic Brain Injury.

BACKGROUND: Numerous mortality prediction tools are currently available to assist patients with moderate to severe traumatic brain injury (TBI). However, an algorithm that utilizes various machine learning methods and employs diverse combinations of features to identify the most suitable predicting outcomes of brain injury patients in the intensive care unit (ICU) has not yet been well-established. METHOD: Between January 2016 and December 2021, we retrospectively collected data from the electronic medical records of Chi Mei Medical Center, comprising 2260 TBI patients admitted to the ICU. A total of 42 features were incorporated into the analysis using four different machine learning models, which were then segmented into various feature combinations. The predictive performance was assessed using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve and validated using the Delong test. RESULT: The AUC for each model under different feature combinations ranged from 0.877 (logistic regression with 14 features) to 0.921 (random forest with 22 features). The Delong test indicated that the predictive performance of the machine learning models is better than that of traditional tools such as APACHE II and SOFA scores. CONCLUSION: Our machine learning training demonstrated that the predictive accuracy of the LightGBM is better than that of APACHE II and SOFA scores. These features are readily available on the first day of patient admission to the ICU. By integrating this model into the clinical platform, we can offer clinicians an immediate prognosis for the patient, thereby establishing a bridge for educating and communicating with family members.

A Computer-Assisted System for Early Mortality Risk Prediction in Patients with Traumatic Brain Injury Using Artificial Intelligence Algorithms in Emergency Room Triage.

Traumatic brain injury (TBI) remains a critical public health challenge. Although studies have found several prognostic factors for TBI, a useful early predictive tool for mortality has yet to be developed in the triage of the emergency room. This study aimed to use machine learning algorithms of artificial intelligence (AI) to develop predictive models for TBI patients in the emergency room triage. We retrospectively enrolled 18,249 adult TBI patients in the electronic medical records of three hospitals of Chi Mei Medical Group from January 2010 to December 2019, and undertook the 12 potentially predictive feature variables for predicting mortality during hospitalization. Six machine learning algorithms including logistical regression (LR) random forest (RF), support vector machines (SVM), LightGBM, XGBoost, and multilayer perceptron (MLP) were used to build the predictive model. The results showed that all six predictive models had high AUC from 0.851 to 0.925. Among these models, the LR-based model was the best model for mortality risk prediction with the highest AUC of 0.925; thus, we integrated the best model into the existed hospital information system for assisting clinical decision-making. These results revealed that the LR-based model was the best model to predict the mortality risk in patients with TBI in the emergency room. Since the developed prediction system can easily obtain the 12 feature variables during the initial triage, it can provide quick and early mortality prediction to clinicians for guiding deciding further treatment as well as helping explain the patient's condition to family members.

New diagnosis of cancer in mild and moderate/severe traumatic brain injury patients in a 12-year population-based study.

BACKGROUND: Traumatic brain injury (TBI) has been reported as a risk factor for brain cancer development. However, the magnitude of the impact of TBI on systemic cancer development has not been clarified. METHODS: A retrospective longitudinal cohort study was conducted using the Taiwan Longitudinal Health Insurance Database between January 2000 and December 2011. A total of 35,306 patients were initially enrolled, and 14,795 patients with mild TBI and 14,795 patients with moderate/severe TBI were matched using the National Health Insurance Research Database in Taiwan. The Cox proportional hazard regression model was used to estimate the hazard ratio (HR) of TBI adjusted for potential confounding factors. RESULTS: After matching, the results showed that patients with moderate/severe TBI had a high mortality rate (17.7% vs. 10.4%) and shorter time interval from TBI to death (mean 3.6 years vs. 5.8 years). No differences were observed in cancer incidence (4.1% vs. 4.1%) or risk factors for mortality between mild and moderate/severe TBI patients. However, patients aged between 46 and 55 years, female patients, and patients with pre-existing renal disease had a significant higher cancer incidence risk in moderate/severe TBI compared with mild TBI patients. The top 15 most common cancers showed that mild TBI patients had a higher percentage of head and neck cancer. The overall mortality rate in all TBI patients diagnosed with cancer was about 50%, and the cancer-specific mortality is approximately 85% in death of TBI patients with cancer. CONCLUSIONS: We concluded that the incidence risk of a new cancer diagnosis and mortality risk of TBI patients with cancer between the mild TBI and moderate/severe TBI patients were not significantly different.

Ceftriaxone therapy attenuates brain trauma in rats by affecting glutamate transporters and neuroinflammation and not by its antibacterial effects.

BACKGROUND: Ceftriaxone is a ß-lactam antibiotic used to treat central nervous system infections. Whether the neuroprotective effects of ceftriaxone after TBI are mediated by attenuating neuroinflammation but not its antibacterial actions is not well established. METHODS: Anesthetized male Sprague-Dawley rats were divided into sham-operated, TBI + vehicle, and TBI + ceftriaxone groups. Ceftriaxone was intraperitoneally injected at 0, 24, and 48 h with 50 or 250 mg/kg/day after TBI. During the first 120 min after TBI, we continuously measured heart rate, arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure. The infarct volume was measured by TTC staining. Motor function was measured using the inclined plane. Glutamate transporter 1 (GLT-1), neuronal apoptosis and TNF-α expression in the perilesioned cortex were investigated using an immunofluorescence assay. Bacterial evaluation was performed by Brown and Brenn's Gram staining. These parameters above were measured at 72 h after TBI. RESULTS: Compared with the TBI + vehicle group, the TBI + ceftriaxone 250 mg/kg group showed significantly lower ICP, improved motor dysfunction, reduced body weight loss, decreased infarct volume and neuronal apoptosis, decreased TBI-induced microglial activation and TNF-α expression in microglia, and increased GLT-1 expression in neurons and microglia. However, the grades of histopathological changes of antibacterial effects are zero. CONCLUSIONS: The intraperitoneal injection of ceftriaxone with 250 mg/kg/day for three days may attenuate TBI by increasing GLT-1 expression and reducing neuroinflammation and neuronal apoptosis, thereby resulting in an improvement in functional outcomes, and this neuroprotective effect is not related to its antibacterial effects.

Rosmarinic Acid, a Bioactive Phenolic Compound, Inhibits Glutamate Release from Rat Cerebrocortical Synaptosomes through GABAA Receptor Activation.

Rosmarinic acid, a major component of rosemary, is a polyphenolic compound with potential neuroprotective effects. Asreducing the synaptic release of glutamate is crucial to achieving neuroprotectant's pharmacotherapeutic effects, the effect of rosmarinic acid on glutamate release was investigated in rat cerebrocortical nerve terminals (synaptosomes). Rosmarinic acid depressed the 4-aminopyridine (4-AP)-induced glutamate release in a concentration-dependent manner. The removal of extracellular calcium and the blockade of vesicular transporters prevented the inhibition of glutamate release by rosmarinic acid. Rosmarinic acid reduced 4-AP-induced intrasynaptosomal Ca2+ elevation. The inhibition of N-, P/Q-type Ca2+ channels and the calcium/calmodulin-dependent kinase II (CaMKII) prevented rosmarinic acid from having effects on glutamate release. Rosmarinic acid also reduced the 4-AP-induced activation of CaMKII and the subsequent phosphorylation of synapsin I, the main presynaptic target of CaMKII. In addition, immunocytochemistry confirmed the presence of GABAA receptors. GABAA receptor agonist and antagonist blocked the inhibitory effect of rosmarinic acid on 4-AP-evoked glutamate release. Docking data also revealed that rosmarinic acid formed a hydrogen bond with the amino acid residues of GABAA receptor. These results suggested that rosmarinic acid activates GABAA receptors in cerebrocortical synaptosomes to decrease Ca2+ influx and CaMKII/synapsin I pathway to inhibit the evoked glutamate release.

A novel wireless optical technique for quantitative evaluation of cerebral perfusion pressure in a fluid percussion animal model of traumatic brain injury.

BACKGROUND: Cerebral perfusion pressure (CPP) calculated by mean arterial pressure (MAP) minus intracranial pressure (ICP) is related to blood flow into the brain and reflects cerebral ischemia and oxygenation indirectly. Near-infrared spectroscopy (NIRS) can assess cerebral ischemia and hypoxia non-invasively and has been widely used in neuroscience. However, the correlation between CPP and NIRS, and its potential application in traumatic brain injury, has seldom been investigated. METHODS: We used a novel wireless NIRS system and commercial ICP and MAP devices to assess the trauma to rat brains using different impact intensity. The relationship between CPP and NIRS parameters with increasing impact strength were investigated. RESULTS: The results showed that changes in CPP (∆CPP), oxy-hemoglobin {∆[HbO2]}, total-hemoglobin {∆[HbT]}, and deoxy-hemoglobin were inversely proportional to the increase in impact intensity, and the correlations between ∆CPP, NIRS parameters {∆[HbO2], and ∆[HbT]} were significant. CONCLUSIONS: The NIRS system can assess cerebral ischemia and oxygenation non-invasively and changes of HbO2 and HbT may be used as reference parameters to assess the level of CPP in an animal model of traumatic brain injury.

The neuroprotective effects of AMN082 on neuronal apoptosis in rats after traumatic brain injury.

BACKGROUND: The aim of this study was to investigate whether AMN082 exerts its neuroprotective effect by attenuating glutamate receptor-associated neuronal apoptosis and improving functional outcomes after traumatic brain injury (TBI). METHODS: Anesthetized male Sprague-Dawley rats were divided into the sham-operated, TBI + vehicle, and TBI + AMN082 groups. AMN082 (10 mg/kg) was intraperitoneally injected 0, 24, or 48 h after TBI. In the 120 min after TBI, heart rate, mean arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) were continuously measured. Motor function, the infarct volume, neuronal nitrosative stress-associated apoptosis, and N-methyl-D-aspartate receptor 2A (NR2A) and NR2B expression in the pericontusional cortex were measured on the 3rd day after TBI. RESULTS: The results showed that the AMN082-treated group had a lower ICP and higher CPP after TBI. TBI-induced motor deficits, the increase in infarct volume, neuronal apoptosis, and 3-nitrotyrosine and inducible nitric oxide synthase expression in the pericontusional cortex were significantly improved by AMN082 therapy. Simultaneously, AMN082 increased NR2A and NR2B expression in neuronal cells. CONCLUSIONS: We concluded that intraperitoneal injection of AMN082 for 3 days may ameliorate TBI by attenuating glutamate receptor-associated nitrosative stress and neuronal apoptosis in the pericontusional cortex. We suggest that AMN082 administration in the acute stage may be a promising strategy for TBI.

Fingolimod inhibits glutamate release through activation of S1P1 receptors and the G protein ßγ subunit-dependent pathway in rat cerebrocortical nerve terminals.

Fingolimod, a sphingosine-1-phosphate (S1P) receptor modulator approved for treating multiple sclerosis, is reported to prevent excitotoxic insult. Because excessive glutamate release is a major cause of neuronal damage in various neurological disorders, the effect of fingolimod on glutamate release in rat cerebrocortical nerve terminals (synaptosomes) was investigated in the current study. Fingolimod decreased 4-aminopyridine (4-AP)-stimulated glutamate release and calcium concentration elevation. Fingolimod-mediated inhibition of 4-AP-induced glutamate release was dependent on extracellular calcium, persisted in the presence of the glutamate transporter inhibitor DL-TBOA or intracellular Ca2+-releasing inhibitors dantrolene and CGP37157, and was prevented by blocking vesicular transporters or N- and P/Q-type channels. Western blot and immunocytochemical analysis revealed the presence of S1P1 receptor proteins in presynaptic terminals. Fingolimod-mediated inhibition of 4-AP-induced glutamate release was also abolished by the sphingosine kinase inhibitor DMS, selective S1P1 receptor antagonist W146, Gi/o protein inhibitor pertussis toxin, and G protein ßγ subunit inhibitor gallein; however, it was unaffected by the adenylyl cyclase inhibitor SQ22536, protein kinase A inhibitor H89, and phospholipase C inhibitor U73122. These data indicate that fingolimod decreases glutamate release from rat cerebrocortical synaptosomes by suppressing N- and P/Q-type Ca2+ channel activity; additionally, the activation of presynaptic S1P1 receptors and the G protein ßγ subunit participates in achieving the effect.

Antioxidative effect of DJ-1 is enhanced in NG108-15 cells by DPMQ-induced copper influx.

Disruption of copper homeostasis is closely involved in neurodegenerative disorders. This study examined whether a hybrid copper-binding compound, (E)-2-(4-(dimethylamino)phenylimino)methyl)quinolin-8-ol (DPMQ), is able to protect NG108-15 cells against oxidative stress. We found that treatment of cells with rotenone or hydrogen peroxide increased cellular oxidative stress and resulted in mitochondrial dysfunction and apoptosis. The cellular levels of Nrf2 and the Cu2+ chaperone DJ-1 were also decreased. These oxidative detrimental effects were all inhibited when cells were cotreated with DPMQ. DPMQ increased cellular Cu2+ content, DJ-1 protein level, superoxide dismutase (SOD) activity, and Nrf2 nuclear translocation under basal state. The activity of SOD decreased under redox imbalance and this decrease was blocked by DPMQ treatment, while the protein level of SOD1 remained unaltered regardless of the oxidative stress and DPMQ treatment. Using endogenous proteins, coimmunoprecipitation showed that DJ-1 bound with SOD1 and Nrf2 individually. The amount of Nrf2, bound to DJ-1, consistently reflected its cellular level, while the amount of SOD1, bound to DJ-1, was potentiated by DPMQ, being greater in the basal state than under redox imbalance. Simultaneous inclusion of nonpermeable Cu2+ chelator tetrathiomolybdate or triethylenetetramine during DPMQ treatment blocked all aforementioned effects of DPMQ, showing that the dependency of the effect of DPMQ on extracellular Cu2+. In addition, silencing of DJ-1 blocked the protection of DPMQ against oxidative stress. Taken all together, our results suggest that DPMQ stabilizes DJ-1 in a Cu2+-dependent manner, which then brings about SOD1 activation and Nrf2 nuclear translocation; these together alleviate cellular oxidative stress.

The Short-Term Effects of Isolated Traumatic Brain Injury on the Heart in Experimental Healthy Rats.

BACKGROUND: To date, cardiac dysfunction after traumatic brain injury (TBI) has not been consistent. In this study, we hypothesized that TBI may play a role in the development of new-onset cardiac dysfunction in healthy experimental rats. MATERIALS AND METHODS: Anesthetized healthy male Sprague-Dawley rats were divided into two groups: a sham-operated control group and a TBI group. The brain was injured with 2.4 atm percussion via a fluid percussion injury model. During the 120 min after TBI, we continuously measured brain parameters, including intracranial pressure (ICP) and cerebral perfusion pressure (CPP), and cardiac parameters, such as heart rate (HR), inter-ventricular septum dimension (IVSD), left ventricular internal dimension diastole (LVIDd), end-diastolic volume (EDV), ejection fraction (EF), fractional shortening (FS), and LV mass diastole (LVd mass) by cardiac echo. On days 1, 3, 7, and 14 after TBI, the brain damage volume was evaluated with triphenyltetrazolium chloride; the physiological parameters of the heart, including HR, IVSd, LVIDd, EDV, EF, FS, and LVd mass, were evaluated with cardiac echo; the morphology of cardiomyocytes was examined by hematoxylin and eosin (HE) and Masson trichrome staining; and the biomarkers of cardiac injury troponin I and B-type natriuretic peptide (BNP) were also examined. RESULTS: Compared to sham-operated controls, the TBI groups had higher ICP, lower CPP, and higher brain neuronal apoptosis and infarction contusion volume. The impact of TBI on heart function showed hyperdynamic response trends in IVSd, LVIDd, EDV, EF, FS, and LVd mass within 30 min after TBI; however, EF and FS exhibited eventual decreasing trends. Simultaneously, the values of the biomarkers troponin I and BNP were within normal limits, and HE and Mass trichrome staining revealed no significant differences between the sham-operated control group and the TBI group. CONCLUSIONS: Our results suggest that TBI due to 2.4 atm fluid percussion injury in healthy experimental rats may cause significant damage to the brain and affect the heart function as investigated by cardiac echo but not as investigated by HE and Masson trichrome stainings or troponin I and BNP evaluation.

Xanthohumol, an active constituent from hope, affords protection against kainic acid-induced excitotoxicity in rats.

Excitotoxicity induced by excessive glutamate has been implicated in many brain disorders. Xanthohumol is a natural product derived from hops (Humulus lupulus L.), which is reported to have glutamate release-inhibiting activity. However, it is unknown whether xanthohumol has protective effects against glutamate-induced excitotoxicity. This study investigated the potential action of xanthohumol in a rat model of excitotoxicity induced by intraperitoneal injection of kainic acid (KA). Xanthohumol (10 or 50 mg/kg) administrated intraperitoneally 30 min prior to KA (15 mg/kg) considerably ameliorated KA-induced seizures, glutamate concentration elevation, and CA3 neuron death. The decrease of mitochondrial fusion protein Mfn-2 and antiapoptotic protein Bcl-2 expression in hippocampal tissues following KA injection were reversed by xanthohumol. Moreover, apoptotic protease activating factor 1 (Apaf-1) expression and caspase-3 activation in the hippocampus were inhibited by xanthohumol. These results suggest that xanthohumol up-regulates Mfn-2 and Bcl-2 to preserve mitochondrial function and suppress Apaf-1 and caspase-3 activation, thereby increasing neuron survival in rats after KA treatment. Therefore, xanthohumol has great potential for development into a therapeutic agent for improving glutamate-related nervous system diseases.

Relative D3 vitamin deficiency and consequent cognitive impairment in an animal model of Alzheimer's disease: Potential involvement of collapsin response mediator protein-2.

Alzheimer's disease (AD) starts with memory impairments that can be observed before the appearance of significant neuropathology; thus, identifying mechanisms to stop AD progression is an urgent priority. Epidemiological and clinical data show that the consequences of vitamin D deficiency are relevant to disease risk and can be observed in the progression of many diseases, especially AD, whereas higher serum levels of vitamin D are associated with better cognitive test performance. However, the potential therapeutic strategy and underlying mechanisms of vitamin D supplementation against AD still need to be further investigated. In the present study, we found that 3xTg-AD mice with vitamin D supplementation exhibited an increase in serum vitamin D concentrations and improved cognition. We measured serum vitamin D binding protein (VDBP) concentrations and found that serum VDBP levels were increased in 3xTg-AD mice compared to B6129S control mice, but there was no significant difference between control- and vitamin D-treated 3xTg-AD groups. The vitamin D-mediated memory improvement may be accompanied by the suppression of increased hippocampal collapsin response mediator protein-2 (CRMP2) phosphorylation, and the restoration of CRMP2 phosphorylation by okadaic acid (OA) could abolish the beneficial effects of vitamin D. In addition, we found that CRMP2 was associated with NR2B and PSD-95 in 3xTg-AD mice with vitamin D supplementation. This CRMP2-NR2B interaction could be disrupted by a TAT-CBD3 peptide or OA, leading to attenuated memory protection in vitamin D-treated 3xTg-AD mice. Therefore, CRMP2 may be involved in vitamin D-mediated memory improvement in AD.

The Neuroprotective Effects of Simvastatin on High Cholesterol Following Traumatic Brain Injury in Rats.

BACKGROUND: High cholesterol has been correlated with a greater risk of cerebrovascular diseases. Whether pre-existing high cholesterol exacerbates traumatic brain injury (TBI), and whether treatment with the cholesterol-lowering agent simvastatin has neuroprotective effects, especially anti-neuroinflammatory effects, after TBI are not well investigated. METHODS: Five-week-old male Sprague-Dawley rats were fed a high-fat diet for 8 weeks to induce hypercholesterolemia. Anesthetized male Sprague-Dawley rats were divided into 5 groups, including the sham-operated control, TBI control, and TBI with simvastatin treatment (4 mg/kg, 10 mg/kg, or 20 mg/kg) groups. Simvastatin was intraperitoneally injected at 0, 24, and 48 hours after TBI. Motor function was measured using an inclined plane. Neuronal apoptosis (maker Neu-N, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling), tumor necrosis factor-α expression in microglia (marker OX42) and astrocytes (marker glial fibrillary acidic protein), and Tumor necrosis factor-alpha receptor (TNFR) 1 and TNFR2 expression in neurons in the ischemic cortex were investigated using an immunofluorescence assay. All of the parameters were measured on the third day after TBI. RESULTS: TBI significantly increased the serum levels of cholesterol. The TBI-induced motor deficit was significantly attenuated by 4, 10, and 20 mg/kg simvastatin therapy on the third day after TBI. TBI-induced neuronal TNFR1 activation and apoptosis, as well as tumor necrosis factor-α expression in astrocytes in the ischemic cortex, were significantly attenuated by simvastatin, particularly when 20 mg/kg was administered. Simultaneously, the serum cholesterol remained high despite simvastatin treatment. CONCLUSIONS: The neuroprotection effects of simvastatin on the pre-existing hypercholesterolemia during TBI in rats may be related to its anti-neuroinflammatory effects but not to its cholesterol-lowing effects.

In-Hospital Mortality After Spinal Surgery in Hemodialysis Patients: An 11-Year Population-Based Study.

BACKGROUND: Patients with end-stage renal disease (ESRD) are at an increased risk of surgical mortality. We aimed to investigate the factors associated with in-hospital mortality in patients with ESRD who underwent spinal surgery, which remains to be determined. MATERIAL AND METHODS: An age- and sex-matched cohort study was conducted using the Taiwan Longitudinal Health Insurance Database between January 2000 and December 2012. Kaplan-Meier curves were plotted with log-rank test to compare the differences between these 2 groups. The Cox proportional hazard model was used to estimate the hazard ratio of in-hospital mortality adjusted with potential confounding. RESULTS: In total, 4109 participants with pre-existing ESRD and 8218 patients without ESRD were included. The in-hospital mortality in ESRD (10.17%) was greater than without ESRD (1.39%). Spinal surgery patients with pre-existing ESRD had a 6.78-fold increase in-hospital mortality risk compared with those without ESRD. Spinal surgery patients with ESRD of any age, male or female, and comorbidities experienced a greater incidence of hospital mortality. In patients with ESRD, operations on spinal cords and spinal canal structures had the greatest hospital mortality (14.87%) compared with spinal fusion (3.46%) or excision or destruction of intervertebral disc (3.01%). Kaplan-Meier survival curves showed that patients with ESRD experienced greater hospital mortality than patients without ESRD in all 3 spinal surgery methods (log rank P < 0.0001). CONCLUSIONS: Spinal surgery patients with ESRD have greater in-hospital mortality than patients without ESRD. Age, sex, history of comorbidities, and types of surgical methods were associated with greater in-hospital mortality among patients with ESRD.

Probability of New-Onset Cancer Between Patients with Traumatic Brain Injury and a Comparison General Population Cohort.

BACKGROUND: Traumatic brain injury (TBI) has been reported as a risk factor for the development of brain tumors. However, whether TBI affects systemic cancer remains to be determined. We investigated the incidence and factors associated with cancer development in patients with TBI. METHODS: A propensity score (age, gender, and comorbidity)-matched longitudinal cohort study of 34,556 patients with pre-existing TBI and 69,112 patients without TBI from January 2000 to December 2015 was presented using the Taiwan's National Health Insurance Research Database. The Cox proportional hazard regression model was used to estimate the hazard ratio of developing cancer adjusted by the potential confounding factors. The stratified analysis of age, gender, and comorbidities for each cancer type was evaluated using forest plot analysis. RESULTS: The cancer incidence rate in the patients with TBI (4.38%) was greater than that in patients without TBI (3.88%). The interval to cancer development in those with TBI (5.65 ± 3.58 years) was shorter than that in those without TBI (6.02 ± 3.65 years). The cancer risk in those with TBI was increased 1.27-fold compared with that in the general population. Of the patients with TBI, age <55 years and male gender indicated a greater incidence of cancer than that of the general population. The patients with TBI had greater cancer frequencies in the head and neck structures compared with those in the general population. CONCLUSIONS: TBI is a risk factor for cancer development, especially in males and those aged <55 years. We hope this information will remind physicians to consider the long-term effects of TBI on cancer development.

Traumatic Brain Injury Increases the Risk of Major Adverse Cardiovascular and Cerebrovascular Events: A 13-Year, Population-Based Study.

BACKGROUND: Previous studies have indicated traumatic brain injury (TBI) as a risk factor for stroke and myocardial injury. Whether TBI increases new onset of major adverse cardiovascular and cerebrovascular events (MACCE) is not well established. METHODS: Patients with a diagnosis of TBI from 2000 to 2012 were 1:2 age-, sex-, and age-adjusted comorbidities matched with normal population cohorts. The MACCE, which included coronary artery disease, heart failure and arrhythmia, ischemic and hemorrhagic stroke, and death, was defined as one inpatient admission with MACCE diagnosis. The maximum follow-up duration to MACCE after the initial TBI diagnosis was 5 years. The baseline comorbidities before TBI, including hypertension, diabetes mellitus, renal disease, and liver disease, also were considered to estimate the risk of MACCE. RESULTS: In total, 16,211 patients with TBI and 32,422 people from the control group were enrolled in the current study. Our results showed that patients with TBI had a 2.77-fold risk of MACCE, 1.72-fold risk of cardiovascular disease, 2.10-fold risk of ischemic stroke, 6.02-fold risk of hemorrhagic stroke, and 3.13-fold risk of mortality compared with the control group (all P < 0.0001) after adjusting the confounding factors. In addition, the trend of cumulated incidence risk among MACCE, cardiovascular disease, ischemic and hemorrhagic stroke, and mortality presented the greatest incidence within the first year after diagnosis and persisted during the 5 years of follow-up. CONCLUSIONS: Our results showed that patients with TBI have a significantly greater risk of MACCE than the control group. We hope this information will remind critical-care physicians and neurosurgeons to keep in mind the long-term effects of TBI on MACCE.

How to Deal with the Empty Space After Organ Removal for Transplantation: A Single Medical Center Experience.

OBJECTIVE: Dealing with the empty space after organ removal for transplantation has not been investigated. METHODS: From January 28, 2005, to November 21, 2017, 111 organ donors were enrolled in this study. They were divided into 3 groups: no replacement, replaced with paper printed with organ graphics, or replaced with 3-dimensional (3D) printed simulated organs. The organs were removed at different periods. The donor's age, gender, etiology of admission, characteristics, clinical pictures, time interval between admission and date of donation, and time interval between donor coordinator consultations were evaluated. RESULTS: A total of 82 men and 29 women with mean age of 43 ± 15.1 years were enrolled. Overall, 329 organs and 126 corneas were transplanted. The major causes of brain death were traumatic brain injury (44.1%) and cerebrovascular disease (32.4%). Twelve donors initially presented with out-of-hospital cardiac arrest. Ten patients with solid cancers and 3 with septic shock donated both of their corneas. The mean time interval between donor coordinator and social worker consultation to organ donation was 3 (2-5 days) (median [interquartile range]). Periods I and II averaged 7-8 donors per year. Fourteen donors and 41 organs were replaced with 3D-printed simulated organs at the families' request in 1 year. CONCLUSIONS: This is the first study to provide a replacement method dealing with the empty space after organ removal. We used 3D-printed simulated organs in addition to providing grief assistance and spiritual support. It also has the potential effect of increasing the organ donation rate.

The Risk of Traumatic Brain Injury Occurring Among Patients with Parkinson Disease: A 14-Year Population-Based Study.

BACKGROUND: Previous studies have implicated traumatic brain injury (TBI) as a risk factor for Parkinson disease (PD). However, the incidence risk of new-onset TBI among patients with PD is not well established. This study investigated the contribution of PD to new-onset TBI associations. METHODS: The study selected 6076 patients with PD and using 1:2 propensity score matching 12,152 general population cohorts in a longitudinal population database in Taiwan. The Cox proportional hazard regression model was used to estimate the hazard ratio of TBI adjusted with the potential confounding factors. RESULTS: The incidence of TBI in patients with PD (2.57%) and compared cohorts (1.81%) was significantly different (P = 0.0007). Patients with PD had a higher risk of TBI (hazard ratio, 1.63; 95% confidence interval, 1.32-2.01) compared with the general population. Patients with PD with TBI incidence had a higher Charlson Comorbidity Index than did the general population with TBI (P < 0.0001). Fall is the major cause of TBI in patients with PD. CONCLUSIONS: This study shows that patients with PD have a high risk of TBI, and the major cause of TBI in patients with PD is fall.

The Effects of Memantine on Glutamic Receptor-Associated Nitrosative Stress in a Traumatic Brain Injury Rat Model.

BACKGROUND: The main aim of this study is to elucidate whether the neuroprotective effect of memantine, a noncompetitive N-methyl-d-aspartate receptor 2B (NR2B) antagonist, affects neuronal nitrosative stress, apoptosis, and NR2B expression and improves functional outcomes. METHODS: Immediately after the onset of fluid percussion traumatic brain injury (TBI), anesthetized male Sprague-Dawley rats were divided into sham-operated, TBI + vehicle, and TBI + memantine groups. TBI rats were treated with a memantine intraperitoneal injection dose of 20 mg/kg intraperitoneally and then 1 mg/kg every 12 hours intraperitoneally for 6 doses. The motor function, proprioception, infarction volume, and neuronal apoptosis were then measured. Immunofluorescence was used to evaluate astrogliosis, microgliosis, nitrosative stress, and NR2A and NR2B expression in cortical cells. All the parameters were assessed 72 hours after TBI. RESULTS: Compared with the sham-operated controls, the TBI-induced motor and proprioception deficits, and increased infraction volume after TBI were significantly attenuated by memantine therapy. The TBI-induced neuronal apoptosis, astrogliosis, and microgliosis, the numbers of neuronal NO synthase and 3-nitro-l-tyrosine expression in neurons, and inducible NO synthase expression in microglia and astrocyte cells in the ischemic cortex after TBI were significantly improved by memantine therapy. Simultaneously, without affecting the NR2A expression in neuronal cells, the NR2B expression significantly decreased after memantine therapy, as evaluated by an immunofluorescence stain. CONCLUSIONS: Intraperitoneal injection of memantine in the acute stage may ameliorate TBI in rats by affecting NR2B expression and decreasing neuronal apoptosis and nitrosative stress in the injured cortex. These effects might represent 1 mechanism by which functional recovery occurred.